Die Entwicklung neuer thrombolytisch wirksamer Medikamente einer- seits und ein rascher, auch technologisch bedingter Fortschritt moderner Gefasschirurgie andererseits sind notwendige Grunde, um den Wert der medikamentosen Thrombolyse erneut abzufragen. Der potentielle Nut- zen der Wiedereroffnung eines thrombotisch verschlossenen Gefasses muss in einem vertretbaren Verhaltnis zu den potentiellen Gefahren des Verfahrens stehen. Dabei hat sich gezeigt, dass die angiographisch erwie- sene Wiedereroffnung eines Gefasses u.V. nur ein vorubergehender Teil- erfolg ist und in die Beurteilung des Verfahrens unbedingt der langfristi- ge Nutzen, etwa die Haufigkeit postthrombotischer Syndrome oder die Letalitat nach Herzinfarkt, mit einbezogen werden mussen. Vnerlasslich ist daruber hinaus die Analyse der Komplikationen. Dieser Aufgabe hat sich eine Gruppe der auf diesem Gebiete erfah- rensten europaischen Kliniker gestellt und beim Deutschen Hamatolo- gen-Kongress 1983 in Munster in Vortragen und einem langfristig vorbe- reiteten Tischgesprach eine kritische Analyse der derzeitigen Situation gegeben. Vielleicht stellt dieses Buch eine Art abschliessender Wertung der ersten Generation von Thrombolytika - Streptokinase, Vrokinas- dar, wo die zweite Generation - Gewebe-Aktivatoren des fibrinolyti- schen Systems - eben in die klinische Erprobung eingefuhrt werden. Die Herausgeber sind den Autoren fur die konzise und kritische Dar- stellung ihrer Themen zu Dank verpflichtet.

Almost a hundred years passed from the time of the first description of an intracranial aneurysm by Morgagni in 1761 to the year 1859, when Sir William Withey Gull arrived at the conclusion that haemorrhage in the subarachnoid space is caused by ruptured aneurysms. The introduction of lumbar puncture by Quincke 1891 and cerebral angiography by Moniz 1927 made it possible to establish the diagnosis of haemorrhage and its source. In recent decades the problems of treatment have come into prominence, first of all because of the inadequacy of conservative methods of treatment in most of the cases, and from surgical experience and its limitations which became apparent before very long. Because of the erratic development of neurosurgery and vascular surgery, above all, since the technique of microsurgery has been used, the entire removal of the source of haemorrhage has become a possibility, even though there were still quite different views taken regarding the most convenient time for surgical intervention, apart from the prevailing local conditions 134, 143, 144,261. In an up-to-date plan of treatment of subarachnoid haem orrhage (SAH) conservative measures are appropriate for bridging the pre-operative period, and must be considered the only solution in those cases in which the source of haemorrhage cannot be found. As far as the effectiveness of such conservative therapy is con cerned, the rate of re bleeding and the mortality provide sufficient comment.

H. J. Meiselman From the theoretical studies of Dr. Skalak, it is clear that white cells can significantly influence the pressure-time profile of a red cell/white cell suspen sion, and that the presence of even a small amount of relatively rigid white cells can have a profound effect on the filtration pressure during the latter portion of a filtration experiment. Conversely, white cell effects, regardless of their relative rigidity, are shown to have only minimal effects during the very early (i. e., 0-2 seconds) phases of the filtration process. Dr. Chien's experimental data support these theoretical studies, in that white cells of different mechan ical properties exhibit different pressure-time curves; pressure-time data for mixtures of leucocytes show shapes which can be predicted from the behavior of relatively homogeneous cell populations. The insensitivity of the very early portions of the filtration process to white cells is again reflected in the calculations made by Dr. Hanss. Using the nominal dilutions, white cell concentrations and the total volume of filtered cell suspension, he indicates that usually less than 1 pore out of 100 is liable to blockage by white cells. He thus concludes that, at the 1% accuracy level, initial filtration data should not be affected by mechanical pore blockage by white cells. Experimental studies by Dr. Lowe and Dr. Stuart question the WBC insensitivity of the early portion of the filtration process. Using a constant flow system, Dr."

Das Buch berichtet tiber das 1. Hauptthema der 28. Jahrestagung der Deutschen Gesellschaft flir Hamatologie und Onkologie 1983 in Mtinster. Der Zeitpunkt flir eine neue Bestandsaufnahme der Therapie der akuten Leukamien ist gtinstig, da ei- nige, in den 70er Jahren konzipierte Fortschritte inzwischen auf ausreichender Beobachtungszeit der behandelten Patienten beruhen. Die hier mitgeteilten und daB das diskutierten Ergebnisse aus maBgeblichen Zentren und Studien zeigen, Nahziel der kompletten Remission heute bei der Mehrzahl der Patienten zu er- reichen ist und daB dieses das Erreichen des Femziels Heilung flir einen Teil der Pa- tienten bedeutet. Dieser Teil erscheint bei lymphatischem Zelltyp groBer als bei myeloischem und innerhalb der Zelltypen bei Kindem groBer als bei Erwachsenen. Auf dem Weg bis hierher findet sich zunachst der therapeutische Durchbruch bei der Akuten Lymphatischen Leukamie des Kindes mittels Kombinations-Chemo- therapie und prophylaktischer antileukamischer Behandlung des Zentralnervensy- stems. Ihm folgten zahlreiche kleine Schritte der besseren Nutzung der verfligba- ren Chemotherapie durch ihre Intensivierung und Risiko-Anpassung. Parallel hier- zu wurde die Knochenmark-Transplantation hoch entwickelt. Die Immuntherapie fand konsequentere Formen. Wesentliche Altemativen und Modifikationen der Therapie akuter Leukamien befinden sich noch in Erprobung durch vergleichende Studien. Zuktinftiger Fortschritt ist zu sehen in einer Senkung der Frtihletalitat durch rechtzeitigen Therapiebeginn und verbesserte Supportivbehandlung, in der Entwicklung neuer, nicht kreuzresistenter Schemata zur Ausweich-Chemotherapie und ihre Einbeziehung in die primare Induktions- oder Konsolidierungs-Chemo- therapie, schlieBlich in der Erkennung von Risiko-Gruppen auch bei akuter mye- loischer Leukamie und einer Risiko-adaptierten Therapie oder Altemativ-Therapie.

In June 1984 a total of 169 physicians, scientists and students assembled in the now familiar and much-loved lair in the Wilsede Luneberg Heath near Hamburg, Germany, for the sixth biennial conference on Modern Trends in Human Leukaemia. This meeting, conducted by Prof. Rolf Neth in his own inimitable style, has established itself as one ofthe major events in the all too crowded programme of international conferences on leukaemia, cancer and related topics. Some may ponder why, with its "rustic" setting - flies, equine deposits, and lack of easy exit -, Wilsede has such an irresistible and persistent lure for so many of the world's top practitioners ofleukaemia research? The an- swer is, I suspect, a cocktail of Rolfs extraordinary charm, the pleasure of meeting friends and colleagues in a uniquely informal and relaxed atmo- sphere and the special style of the proceedings themselves, which focus on the evaluation of ideas and hypotheses rather than the cataloguing of data.

The hemodynamic significance of the flow properties of blood was put into perspective only during the past decade. Advances in modern technologies today allow the quantitative analy- sis of the fluidity of blood and its components under conditions approximating the flow in vivo, particularly those in the microcirculation. The hematocrit is the most important of the determinants of blood fluidity (reciprocal value of blood viscosity); acute increases in the hematocrit exert deleterious effects on circulation and oxygen transport owing to impaired fluidity of blood. High viscosity of plasma due to hyper- or dysproteinemias initiates the microcirculatory dysfunctions in hyperviscosity syndromes. Furthermore, the fluidity or deformability of red cells might be critically diminished and therefore cause redistribution of blood elements and adversely affect the resistance to flow within the microvessels. In low- flow states blood fluidity most likely becomes the key determinant for microvessel perfu- sion, overriding the neural and local metabolic control mechanisms operative at physiological conditions to adjust blood supply to tissue demand. Microcirculatory disturbances are there- fore encountered whenever driving pressures are reduced, as in shock or hypotension, and distal to stenoses of macrovessels, but also in hemoconcentration due to plasma volume con- traction, polycythemia, leukemia, and dysproteinemia. Based on experimental studies exploring the possibilities and limitations, with regard to improving the fluidity of blood by reducing the hematocrit, the concept of intentional hemo- dilution has been introduced to clinical medicine.

Levy, 10 Po: General Summary of the Meeting 507 Subject Index 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 515 1 Also special Lecture for the Wilsede Joint Meeting on Pediatric Oncolo- gy II 2 Were also presented in the Wilsede Joint Meeting on Pediatric Oncology II 3 Presented in the Wilsede Joint Meeting on Pediatric Oncology II xv Participants of the Meeting Anders, Fritz, Genetisches Institut der Universitaet, Heinrich-ButT-Ring 58-62,6300 Giessen, Federal Republic of Germany Bauer, Georg, Institut fuer Virologie im Zentrum fUr Hygiene, Hermann- Herder-Strasse 11,7800 Freiburg, Federal Republic of Germany Bell, Richard, Medical Oncology University Hospital, 75 East Newton Street, Boston, MA 02062, USA Bernhard, Silke, Dahlem-Konferenzen, Wallotstrasse 19, 1000 Berlin 33, Federal Republic of Germany Bister, Klaus, Max-Planck-Institut fUr Molekulare Genetik, Ihnestrasse 63-73, 1000 Berlin 33, Federal Republic of Germany Blattner, William A. , Family Studies Section, Environmental Epidemiology Branch, National Cancer Institute, Landow Building, Rm. 4C18, 7910 Woodmont Avenue, Bethesda, MD 20205, USA Boiron, Michel, Institut de Recherches sur les Leucemies et les Maladies du Sang, Universite Paris VII, Hopital Saint-Louis, 2 Place du Docteur-Four- nier, 75475 Paris Cedex 10, France Boniver, Jacques, Institut de Pathologie B 23, Laboratoire d'Anatomie, Pathologique, 4000 Liege, Belgium Bornkamm, Georg W. , Institut fuer Virologie im Zentrum fuer Hygiene, Hermann-Herder-Strasse 11,7800 Freiburg, Federal Republic of Germany Burgess, Antony W.

Korperfremde und korpereigene kolloidale Infusionsmittel haben vorrangig in der Notfallmedizin und in der Substitutionstherapie bei definierten humoralen Immundefekten ihren festen Platz. Die heterologen Plasmaersatzmittel bestehen aus Fremdkolloiden wie Dextran, Gelatine und Hydroxyathylstarke und unterschei- den sich untereinander deutlich in ihren physikochemischen Eigenschaften, dem Molekulargewicht, dem Volumeneffekt, der Verweildauer und in ihren Nebenwirkungen. Bei Blutverlusten treten sie an die Stelle der Plasmaproteine und gewahrleisten ein ausreichendes intravasales Volumen. Ausserdem haben sie Ein- fluss auf rheologische und gerinnungsphysiologische Parame- ter. Homologe kolloidale Infusionsmittel, wie die Serumkonserve oder die durch Fraktionierung gewonnenen Plasmaderivate (Plas- maproteinlosungen [PPL], Humanalbumin sowie Immunglobuli- ne), haben zusatzliche Eigenschaften, die therapeutisch genutzt werden konnen. Hauptsachlich ihre Indikationen und Anwen- dungsbereiche wurden auf dem mit Unterstutzung der Firma Bio- test Pharma GmbH im Mai 1981 durchgefuhrten Symposium in Einzelvortragen dargestellt. Von besonderem Interesse war erneut, Indikationsbereiche fur eine passive Immuntherapie zu diskutieren, wobei diesmal nicht die unterschiedlichen Immunglobulinpraparationen im Mittel- punkt standen, sondern die Besprechung der physikochemischen Eigenschaften und die klinische Anwendung der Serumeiweiss- konserve den Vorrang hatte. Wie die Diskussion zeigte, stellt die Serumeiweisskonserve eine wertvolle Alternative zu der Anwen- dung von intravenos applizierten Immunglobulinpraparationen dar. Hierbei werden dem Organismus ausser Immunglobulinen auch wertvolle und notwendige Transportproteine bereitgestellt. Dabei ist die Hepatitissicherheit des kommerziellen Praparats ein entscheidendes Kriterium. V Spezielle Indikationen fur die Applikationen von Immunglobuli- nen bleiben jedoch weiter bestehen und wurden besprochen. Auch der Einfluss von intravenos applizierten Immunglobulinen auf zellvermittelte Immunreaktionen wurde dargestellt.

In recent years immunobiology has witness- aspects on the background of various meth- ed most remarkable achievements and the ods applied, as well as clinicopathologic im- understanding of lymphomas and leukemias plications. A special chapter is addressed to is greatly increased. Knowing that these "Pagetoid Reticulosis" elucidating the neoplasms are essentially immunoprolif- various views on the cytogenesis of this neo- plasm. For the same reason, a contribution erative diseases extended the dermatological views of the corresponding skin tumors. on "Merkel Cell Neoplasms of the Skin" has Sophisticated techniques and new im- been included because these tumors have munological methods now enable us to been mistaken for pagetoid reticulosis. analyze and classify cutaneous malignant The last chapter on "Cooperative Study lymphomas far better than before. As a Groups, Staging and Treatment" leads off consequence this has produced a vast lit- with the signmcant contribution from the erature on this subject in the last few years. Kiel Lymphoma Study Group (G. Brit- For those who are not so familiar with mod- tinger}. 1t deals with the results of a prospec- em immunological thinking, it has become tive study of nodal lymphomas which were increasingly difficult to keep abreast with classilled according to the Kiel Classmca- these developments, and a comprehensive tion. Treatment protocols applied to skin review of this subject appeared to be needed. lymphomas are reported from Cooperative This is the purpose of the present book.

These proceedings are of a symposium held jointly by the UK Haemophilia Centre Directors and the Royal College of Physicians and Surgeons of Glasgow. The purpose of the meeting was to highlight the growing areas of haemophilia care and research as they serve as a model for the study of other disorders. In particular a major section of these proceedings is devoted to the investigation of liver disease in haemophili- an area which offers unique opportunities for both basic, applied and clinical research. The second section considers modern treatment of bleeding disorders and the potential cost to society. With the advent of better standards of care, the requirements of plasma products have risen to such an extent that future predictions suggest a worldwide shortage may occur. The third section of the book discusses the detailed structure of the Factor VIII molecule and its sub-compon( nts and also its functional and immunological characteristics. The availability of amniocentesis and its accuracy in predicting which factor is affected has produced new problems for genetic counselling. The fourth section is clinical and describes the experience of procedures in the Nuffield Department of Orthopaedics, Oxford. For all of us looking after such patients this remains the most important unsolved cI inical problem. C. D. Forbes G. D. O. Lowe vii List of Contributors Professor Charles Abildgaard, Dr. Geijlswijk, Department of Paediatrics, Department of Haematology, 4301 X Street, University Hospital, Sacramento, Utrecht, California 95817 The Netherlands Dr. L.

The origin and function of normal monocytes and macrophages have been clearly defined by extensive investigations in human and in animal models. The central importance ofthis cell system for the biological defense mecha- nisms is well established: phagocytosis, inactivation and destruction of organic and inorganic materials, an important role in the initiation ofhumo- ral and cell mediated immunological responses, and the secretion of a varie- ty of chemical mediator and effector substances are the most important fea- tures of this ontogenetically ancient cell system. However, the data on this cellular system are rather recent, and this may explain why relatively little attention has been payed to the pathology of the monocyte-macrophage system (MMS) until now. In addition, this monograph should focus attention on the secondarypa- thophysiological implications of the MMS in disorders not primarily origi- nating from this system. Several techniques are available to identify even abnormal individuals of this cell system and, therefore, can be employed for the study of severely altered or neoplastic monocytic cells.

In the autumn of 1980, the decision was made by the responsible bodies of the German Society for Medical Documentation, Informatics and Statistics (Deutsche Gesellschaft fUr Medlzinische Dokumentation, Informatik und Statistik e.V.) to make the application of computers in blood banking and blood transfusion one of the topics to be treated at the 8th spring conference of this Society, which was then arranged to take place in TUbingen from April 9-11, 1981. The goal of the con- ference was to unite application specialists and methodologists in order to assess current achievements and identify fields needing further improvement. We were fortunate to obtain the interest of the German Society for Blood Transfusion and Immunohaemat6logy D~. Roos, the head of the EDP Work study group of the Section 1 of this. Society did substantially influence the programme. Many of the papers actually reflect accomplish- ments of his research and of the work study group. We also consider ourselves fortunate to win Prof. C. Mueller-Eckhardt, current president of this Society, to give an introductory address.

Gut ist eine Lehrart, wo man vom Bekannten zum Unbekannten fortschreitet; schon ist sie, wenn sie sokratisch ist, d.i. wenn sie dieselben Wahrheiten aus dem Kopf und Herzen des Zuhorers herausfragt. Bei der ersten werden dem Verstand seine Uberzeugungen in Form abgefordert, bei der zweiten sie ihm abgelockt. Professor Friederich Schiller Jena, in a letter written on 23 February 1793 to his friend and supporter Korner, father of the poet Theodor Korner. Established clinicians and scientists as weil as students aga in tried the Wilsede experiment for three days and nights and learned from each other. In our fourth Wilsede meeting on "Modern Trends in Human Leukemia" we concentrated once again on questions re gar ding the practical application of research and its benefits to the patient. The main emphasis of leukemia research has changed since the first Wilsede meeting in 1973. Virology is no longer the sole interest. Advances in immunology and cell genetics and a better understanding of Dr. h. c. Alfred Toepfer speeking with participants of the meeting in Wilsede XXI Arrival and discussion of participants in front of the meeting pI ace "De Emmenhoff" XXII Personal and scientific discussion in Wilsede June 1980 Fotos: R. Vols XXIII the mechanisms regulating normal and pathological blood cell differen tiation have had a considerable impact on the direction of leukemia research."

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.

Platelet transfusion has become an integral part of the management of disseminated malignant disease and its role in preventing or controlling haemorrhage due to thrombocytopenia is now without dispute. This monograph contains articles presented at an Inter national Symposium on Platelet Transfusion held in London in July 1978. It is hoped that they provide an up to-date review of the preparation and laboratory function of platelet concentrates in addition to practical advice towards developing an intelligent approach towards their administration. T.A. Lister j.S. Malpas 9 1 Platelet Collection and Quality Control D. Huestis In this chapter I would like to discuss platelet collection tcchniqlll" and q ualit \7 control; the more clinical aspects will be covered by otl)(, l contributors. In the first place it would be prekrable to l()()k .11 platelets from the point ofvin" of the physician lIsingthern - whatlw needs to know so that his usc of platelets will he intelligent and directed by bac kground knowledge of vvhere platelets are found. hcm they arc halYested and stored. and the clinical realities of platekt t ranslilsion. The platelets we transfuse tomorrow walk the streets today. Intelligent donor recruitment and public information carnpaigm about blood donation, and about new systems of blood donation that arc not yet familiar to the general public, need to be broadcast and developed, but are not really a subject of discussion for this meeting. HISTORICAL REVIEW I shall start with an historical perspective on the evolution of platelet transfusion."

Dr W J Jenkins In 1977 when the Sheffield Transfusion Centre took delivery of the first GROUPAMATIC blood grouping machine in the UK it was equipped with a sample identification system involving complicated and expensive disposable punched cards. In fact, the cards were so expensive that Dr Wagstaff was unable to find the revenue to support the system. A year later, when Brentwood took delivery of a GROUPAMATIC, we were faced with the same problem, but by chance we heard that KONTRON was developing a laser scanning system for bar code labels and we were able to have our machine modified. Subsequently the Sheffield machine was altered to take the bar code scanner. At about the same time the Bristol Centre was helping TECHNICON with the development of the AUTO GROUPER C-16, and fortunately they decided on a laser reader of the same type for bar code identification. Thus there were three centres with the capability for reading bar codes on blood grouping machines and it became necessary to find someone to produce the bar code labels. There was only on~ printer in the UK who could produce labels to the required specification. To cut the costs of printing, and in the hope of avoiding a wide variation in codes, I invited representatives of centres interested in the problem to a meeting, where we set up what we called the Group of Six. This later became an official Working Party of the Regional Transfusion Directors.

This volume contains papers and discussions of the Vlth Dialyse-Arzte Workshop, which was held in Bernried at Lake Starnberg near Munich the 5th and 6th of March 1980. Generous- ly sponsored by Travenol, Munich, the Dialyse-Arzte meetings now have a tradition spanning 16 years. According to the con- stitution of these meetings, the topics of earlier years had to cover dialysis and related fields. Thus the sponsor requested that this year also one lecture - incorporated here as part - should deal with the state of art of dialysis, thereby hopefully linking this Workshop to the previous meetings. Dialysis techniques of the 1960s, pioneered by many of attend- ing speakers and panelists (see List of Contributors), have never come to a standstill. Indeed, vascular access and extra- corporeal circulation have become routine for the nephrologist and have made possible the introductimn of new approaches, such as hemofiltration and hemoperfusion. Also today new membrane technologies provide us with a potentially even more effective therapeutic tool, namely plasma separation.

Research on aplastic anaemia has until recently been limited to clinical description, morphology and epidemiology. New methods to culture haemopoietic cells, and advances in our knowledge of proliferation and differentiation in the haemopoietic cell system .opened a new area of scientific interest for this "prototype" of haemopoietic failure. In addition, bone marrow transplantation became not only a clinical method of treatment, but also a source of data useful for the discussion of pathophysiological models of aplastic anaemia. This situation prompted us to arrange an international con ference on aplastic anaemia, with particular emphasis on its patho physiology and the rationals of the current therapeutic approaches. This conference was held at Schloss Reisensburg from July 20-22, 1978 with the participation of both experimental and clinical scientists active in this field or in related areas of research. The proceedings of the symposion reflect the present knowledge as well as the many new questions which arose from the discussions. The editors are gratefully indebted to the participants of this meeting, to Gerlinde Trogele and all the co-workers of the Uni versity of Ulm engaged in preparation of this symposium and of this volume, and last not least to all sponsors who provided the financial basis for this scientific event."

The contact between the human blood and foreign technical apparatus (circulatory) and respiratory assist devices, arti ficial kidneys) leads to changes in the plasmatic and cel lular components of the blood, which have often only been taken as signs of gross but passive blood destruction. There is much evidence to support this notion in parts (mechanical cellolysis of erythrocytes and thrombocytes), however, these changes have to be seen in a broader bio logical context as an organ-specific reaction of the blood. It is an unjustified oversimplification to simply treat the blood as transport organ for respiratory gases (02 and CO ) and metabolites. The blood is rather also an organ 2 system for specific and unspecific defense mechanisms, di rected against the hazards of mechanical, microbiological and toxicological risks posed to multicellular macro-orga nisms in an environment in which trauma and other distur bances of the physical integrity are common. The two defense systems of the blood are based on humural and cellular constituents; the latter have to be considered as "excitable cells," capable of responding in a predictable and automatic fashion to adequate stimuli. The response of the cellular constituents in controlled and coordinated by chemical mediators. The immunological research of the last century has distinguished two separate defense systems of the blood: I. The highly specific defense system (immune system sen sustrictori) which is phylogenetically new and is ontogenetically learned."

Bone marrow transplantation, the goal which integrates hemato logists, immunologists, geneticists, oncologists and specialists of several other fields, has overcome its state of stagnation in recent years. Clinically as well as experimentally new approaches to old problems and new conclusions from recent findings proliferate: bone marrow transplantation in leukemic remission, bone marrow growth in cell culture, bone marrow manipulation with antisera, bone marrow differentiation in histoincompatible hosts, immuno suppression with partial body irradiation to cite just a few. These and other new developments were discussed by experts from 12 countries in and outside the European Community during an international seminar held on March 8-10, 1979 by the "Institut fur Hamatologie, GSF," under the auspices of the European Communities. The editors thank both the contributors to this symposium, who made it a successful meeting and submitted their manuscripts punctually, and the publishers, who have provided a volume of high quality in good time. They are also grateful for the valuable cooperation from numerous colleagues at the Institut fur Hamato logie."

Even though numerous questions with regard to the pathogenesis of athero sclerosis have not yet been answered, the accumulated evidence indicates significant regression of lesions in experimental animals. This is discussed extensively in this monograph, as are the mechanisms involved in regression of lesions. Whether human atherosclerosis has the potential for regression appears to be the most important, but at the same time the most difficult question to answer. Contrary to experimental atherosclerosis in animals, which can be produced and which can regress within a few months, human lesions in general develop slowly over many years. Therefore, measures aimed at modifying this process may also require many years to be successful. In addition, repeated direct examination of lesions in the human is usually not possible. Nevertheless, recent reports in patients with hyperlipoproteinemias indicate that pronounced and maintained control of hyperlipidemias may lead, even within months, to regression as evidenced by angiography or sophisticated measurements of peripheral circulation. The monograph is divided into two sections. The first will deal with of lipid deposition in the arterial wall, whether "atherogenesis" mechanisms or not there is evidence of monoclonal origin of human atherosclerosis plaques, cell culture and factors that stimulate smooth muscle proliferation, and animal models of atherogenesis. This section is concluded with a discussion of dietary factors other than lipids in atherogenesis."

clinical efficacy of haemostatic agents had to be published work and had to fulftl most of the following minimum requirements: (1) Quantitation ofthe measured blood loss was required, and not merely a clinical impression of the amount of blood lost, if the document pertained to a planned but "open" clinical trial. (2) Only double-blind trials with random allocation of the placebo and experimental drug to preselected patients were considered suitable for discussion, if the blood loss had not been quantitated in a prospective trial. (3) Defmition and appropriate selection of patients admitted to the trial: all inclusion and exclusion criteria used to select patients had to be mentioned in detail. (4) Once included in the trial, patients could be withdrawn only on the basis of strict criteria for withdrawal which had been defined in advance. (5) A double-blind trial had to be continued for an adequate length of time if the haemostatic agent was being assessed in the prevention of bleeding in patients with a long lasting bleeding disorder . (6) A clear and detailed statistical analysis of the results was required. Moreover, a clear distinction between the therapeutic and prophylactic value of the haemostatic agent had to be made and applied separately to the group of patients without any major basic disorder and those with a bleeding disorder e.g. : chronic thrombocytopenia, haemophilia, Rendu-Osler telangiectasia ... General statements not substantiated by experimental data, even when issued by well-known authorities, were not considered a reasonable basis for discussion.

This two-and-a-half-day symposium has concentrated on main aspects of the rapidly expanding field ofleukocyte markers in hematology. While leukemias are already being 'phenotyped' routinely in clinical centers, continued research on the developmental sta ge of cells and cell membranes, expanding into a malignant clone, permits new snap shots on hemopoietic differentiation. Thus the discovery of leukemia-associated anti gens, which so far have not been found on subpopulations of normal cells, has greatly stimulated the discussion on 'differentiation antigens versus tumor antigens'. The proceedings reflect the considerable success which has been achieved very re cently in the classification of hemoblastomas. Consequently the number of leukemias which are unclassifiable by immunological methods have dwindled down to a small mi nority. New facts give rise to new questions. By including the main points of the discussions in the proceedings, we wanted to give the reader an opportunity to get an impression of the questions and conclusions raised and drawn by the participants on the basis of new - and frequently still unpublished - data. The editors thank both the contributors to this symposium, who made it a successful meeting and submitted their manuscripts punctually, and the publishers, who have provided a volume of high quality in good time. They are also grateful for the valuable cooperation from numerous colleages at the Institut fUr Hamatologie.

It is perhaps not too much of an exaggeration to claim that experimental hematology as it flourishes today originated largely from the pioneering attempts to protect lethally radiated animals (I) by shielding of hemopoietic tissues by L. 0. Jacobson (9), and (2) by treatment with bone marrow suspensions by E. Lorenz and his col- laborators (12). The site chosen for this annual meeting of the International Society for Experi- mental Hematology is given a special historic sig- nificance by the fact that it was 25 years ago that the first publication on this subject by Lorenz ap- peared from his laboratory at the National Insti- tutes of Health. Lorenz's discovery marked the beginning of a period which lasted until 1956, during which the protection afforded by hemopoietic cell suspensions was confirmed by many. This soon led to an intensive scientific de- bate on the mechanism of this protective effect: was it due to a humoral factor produced and pro- vided by the bone marrow-as Lorenz The Appearance of postulated-or to transplantation and subsequent proliferation of hemop- etic cells? This question was defini- 1 the Multipotential tively answered in 1956 by evidence from three different laboratories (7, 15, 26), which demonstrated the origin of the cells Hemopoietic in the repopulated tissues using a variety of cellu- lar and immunologic markers. By the same token, these contributions marked the birth of radiation Stem Cell chimeras.

Jean BERNARD * I should like to begin with an assumption and a paradox. The assumption is that leukemia is a disease of a stem cell characterized by pathologie alterations of that cell and its progeny. All present research and discussions are centered around the leukemic cell. So is this symposium, which would not take place except for our primary interest in the leukemic cell. This does not preclude, of course, consideration of other definitions and other approaches to the prOblem. By definition, then, the leukemic cells are abnormal cells and their metabolism and functions are presumed to be abnormal. Yet, the classification of the different types of leukemias is based upon the characteristics of normal cells. We talk of "lymphoblasts" and "myeloblasts" as predominant cell types in leukemia. This leads to a double paradox. In the first pi ace it is clearly illogical to classify abnormal cells by their resemblance to normal cells, since their very abnormality consists in not being normal. Yet, as a second paradox, the classifica ti on has had the happy consequence of ai ding us in the treatment and prognosis of leukemia for the past 25 years. A more detailed analysis shows that the consequence of this paradox are complex: while there exists a useful correlation between cellular types, treatment and prognosis, numerous problems and difficulties persist. The most serious of them concems the "unclassified leukemias" which are the reason for this reunion.