Major epidemiologists from the UK, USA and Europe contribute to the first ever, much needed comprehensive review of the epidemiology of peripheral vascular disease in the lower limbs.

Through numerous discussions with colleagues it became apparent that the time was right to begin a series of workshop-like meetings on myeloid tumorigenesis. Myeloid tumors are the nonlymphocytic tumors of the hematopoietic system which include tumors of the neutrophilic, monocytic, erythrocytic, basophilic (mast cell) and megakaryocytic lineages. Pioneering studies in myeloid tumorigenesis were initially made in chickens with the discovery of retroviruses that induce various kinds of myeloid tumors acutely (myelocytomatosis, myeloblastosis, and erythroblastosis). These avian retroviruses were subsequently shown to contain the oncogenes v-myb, v-~, v-~, v-erbA, or v-erbB. There have been dramatic advances in studying the pathogenesis of hematopoietic tumors in genetically defined mammalian systems. Many of the well developed model systems in inbred mice, have focused on T- and B-1ymphoma development. Although myeloid tumors have been found in mice, they have not been studied as intensively as lymphoid tumors. Possibly this is because myeloid tumors are less common than lymphoid tumors. Recently, there has been renewed interest in murine myeloid tumor systems. This focus has resulted from 1) the discovery of inbred strains of mice (e. g. BXH-2, AKXD- 23, SJL/J) that are highly susceptible to spontaneous or induced myeloid tumorigenesis; 2) establishment of transplantable murine myeloid tumors (e.

The biology of solid tumor metastasis has been the subject of significant scientific and clinical interest for years and while experimental evidence reveals that metastasis is not solely a random event, very little is known about the biology of metastasis originating from prostate cancer. This is in spite of the fact that the majority of prostate cancer patients die with metastatic lesions to the bone. Progress in understanding this most important aspect of prostate cancer has been hampered by the lack of suitable animal models and an inability to accurately quantify bone metastases and their responses to therapy. Over the past decade, scientists in Japan and the United States have steadily advanced our understanding of the cellular, molecular and immunologic biology of primary and disseminated prostate cancer. It is this body of new information, combined with advances in imaging techniques and prostate cancer tumor markers, that prompted the need for an in-depth assessment of bone metastasis of prostate cancer. Accordingly, on December 12, 1990, a group of basic and clinical investigators from Japan and the United States convened in Gotenba, Japan, to hold the first conference devoted solely to the basic biology and clinical aspects of bone metastases originating from prostate cancer. The cross-fertilization of ideas that was fostered through in-depth discussion of technological advances among various basic and clinical disciplines not only further advanced our understanding of prostate metastases to the bone, but suggested approaches for precise quantitative assessment of these lesions and their treatment.

The publication of Platelet-Vessel Wall Interactions, the second monograph in the Bloomsbury Series in Clinical Science, is particu larly welcome as its appearance signifies the further development of the Series and its potential for the future. The theme of this monograph is the pathophysiology of atherosclerosis, a topic that symbolises the aim of the Series, namely to highlight the important interfaces between basic medical science and clinical practice. Our congratulations to the Editors and contributors. London, December 1987 lack Tinker Preface In the Western world, atherosclerosis causes more illness and death than any other disease. Despite its devastating effects, the pathogenesis of the disease remains a matter for hypothesis and con jecture. This monograph owes its conception to a programme of work directed towards understanding the basic pathophysiology of atherosclerosis. The circulatory system is lined by vascular endothelium which has a central role in maintaining the integrity of the vessel wall and prevent ing thrombosis. The natural equilibrium existing between normal en dothelium which supports blood flow, and platelets which serve to re pair damaged endothelium, is explored in the first two chapters. Atherosclerosis developing as a response to endothelial injury is one hypothesis which has stimulated widespread interest, and re search has largely been directed towards finding the injurious agent."

Written by a team of world-leading experts in the field, who have published extensively

For primary care physicians, haematologists, surgeons and other healthcare professionals with an interest in thromboprophylaxis

Discusses both medical and surgical thromboprophylaxis and includes all relevant guidelines for thromboprophylaxis in pregnancy

Thoroughly revised and updated new edition

This second edition of the Handbook of Thromboprophylaxis expands upon the role of anticoagulants in clinical practice. In addition, it summarises key papers in the field and provides evidence-based guidelines for the use of anticoagulants in routine day-to-day practice.

"

While the enzyme cascade that allows coagulation is well known physiologically, its elegant practical examples are vividly demonstrable in the clinical application of blood and components for the treatment of bleeding problems in surgery, trauma or in congenital deficiency in patients. This volume provides the fundamental and recent understanding relating to coagulation pathways, recombinant technology and other methods for coagulation factor production, up to date laboratory assay, preservation of cellular and plasma components, and their clinical use in surgery and medicine, including the immuno response to repeated challenge to contaminating protein in coagulation factor concentrates. The interrelated but multi-disciplinary chapters have been integrated in four sections: Principles and Fundamentals: Mechanism of thrombin formation; structure -- function relationship of coagulation proteins, role of calcium and anticoagulant: blood collection on haemostatic potential of plasma proteins and platelets; Factor VIII yields from anticoagulant exchanged plasma. Preservation Aspects: Platelet function preservation, platelet interaction with vessel wall; trends in the use of coagulation factor concentrate; immuno purification of Factor VIII; structural and fundamental properties of recombinant coagulation factors. Laboratory Aspects: Platelets counting and function testing; platelet crossmatch predictive value; clinical efficacy of platelet concentrate; protein C and protein S; principle of coagulation factor assay; standardisation of clotting factor assays; clinical efficacy of clotting factor concentrates. Clinical Consequences

Between 1950 and 1960, remarkable advances were made in the develQpment Qf antihypertensive drugs, but since then, prQgress has been less rapid. This dQes nQt mean that no. new drugs have been intrQduced: Qn the cQntrary, their number has increased sharply; but since the advent Qf the beta-adrenergic blQckers no. new pharmacQdynamic principle has been discQvered that CQuid be applied widely as an antihypertensive. This has nQt been fQr want Qf effQrts, because many attempts have been made to. find new ways and means Qf influencing blQQd- pressure regulatiQn Qr the mechanisms invQlved in the pathQgenesis Qf hypertensiQn. HQwever, the results Qf these endeavQrs have mQstly been disapPQinting. Even thQugh high blQQd pressure can be treated mQre satisfactQrily tQday than many Qther diseases, the success achieved in cQmbating Qne Qf man's mQst frequent ailments shQuld nQt induce cQmplacency, but rather stimulate research tQwards further imprQvements. The present standstill affQrds an QPPQrtunity to. review the field Qf antihy- pertensive agents, fQr it is unlikely that fundamentally new drugs will appear in the near future. AlthQugh greater knQwledge has been gained Qf the mechanisms Qf blQQd-pressure regulatiQn and Qf the pathQgenesis Qf hypertensiQn, these ad- vances have had no. direct cQnsequences in the search fQr new therapeutics.

J.J. Van Loghem Previously to this symposium, five others have taken place in Groningen. The first one in 1976. This yearly scientific happening has continued. It has greatly stimulated the in terest in blood transfusion and all allied disciplines in our country. It is clear that these meetings are organized not only by a good scientist, but at the same time by a gifted or ganizer who, as director of the Red Cross Blood Bank Gro ningen-Drenthe, has shown that the heavy load of daily routine work can very well be combined with a large amount of experimental and clinical research in blood component therapy, coagulation disorders, blood group genetics and serology, the latter in cooperation with the Blood Group laboratory of the University Hospital Groningen under the directorship of Dr. Van Dijk. All these activities show how much a well-organized blood bank can contribute to a national blood transfusion orga nization."

Due to the topology and structure of the lymph nodes, their role in the pathogenesis and development of diseases is a very special one. Each organ and even each organ-related region of the body has its own group of lymph nodes, specific topological reactions, such as in circumscribed inflammation or in the metastatic spread of malignant tumors. On the other hand, all the lymph nodes of an organism join in a uniform function effected by highly differentiated structures. Volume 84 of Current Topics in Pathology presents our current knowledge about the structure and reaction patterns of this "sec ondary" lymphoid organ. Despite our original intention to publish all the contributions in one book, it became necessary to divide them: Part 1 focuses on the involved nodal compartments, cell types, and functions, while Part 2 describes their reactions in inflammatory, neo plastic, and immune-deficient diseases. Even with the cooperation of more than 30 authors, the coverage cannot be exhaustive. The scope of both parts is limited to those reactions that can be described by direct and indirect morphological methods, including modern tech niques such as immune electron microscopy."

Contents: Introduction and Overview Lymphopoietic Growth Factors: Pathophysiology of T-Cell Mediated Shock Induced by Bacterial Superantigens - Natural Killer Cells and Interleukin-2-Activated Killer Cells - TumourImmunogenicity Induced by Exogenous Interleukins - Cytokine Gene Therapy of Cancer - Analysis of T-Cell Receptor Variability in Tumour Infiltrating Lymphocytes - Clinical Studies with Interleukin-2: An Overview - Clinical Trials with Local Administration of Lymphopoietic Growth Factors - Clinical Trials with Interlaukin-2. The Rome Experience. Haematopoietic Growth Factors: Lymphohaematopoietic Growth Factor Use in Lung Cancer Patients - Clinical Trials with Haematopoietic Growth Factors and Peripheral Blood Stem Cells

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."

Much of the attention presently paid to leukemia is the result of recent progress in understanding and treatment. Chemotherapy of leukemia started in the late 1940s, and combination therapy evolved in the late 1950s. It was at that time that the clonality of leukemia was realized, after the discovery of chromosomal and then biochemical and immunological markers. And now we have the new data on retroviral and cellular oncogenes and the reports on human T -cell lymphoma/ leukemia viruses. Many more steps forward could be enumerated in a field which is so rapidly making the hematological textbooks outdated. In this volume, thirteen in-depth reviews from large multicenter trials in the Federal Republic of Germany summarize the current state of diagnosis and management of leukemias. Childhood ALL and AML adult ALL and AUL were investigated. While cure appears to be achievable for more and more patients with acute leukemia, we still pursue the aim of optimal palliation in chronic leukemias. The management of patients with leukemia therefore varies to a large extent in aggressiveness of therapy. In some situations, rescue from an otherwise lethal disease is provided by bone marrow transplanta tion, which is discussed in two chapters."

The European School of Oncology came into existence to respond to a need for informa tion, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidisciplinary approach which is difficult for the Universi ties to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice.

One of the most fascinating tools at the disposal of the molecular biologist is the medical clinic. The responsibilities of those who provide health care do not stop when they give optimal care to the individual patient and train their successors adequately. They also are under the obligation to obtain maximal information from every case they treat in order to reach a better understanding of the underlying illness in order to improve therapeutic results in the next patient. Fundamental research in pathological material is therefore a medical must as well as an opportunity for scientific work. The scientist working in this field can profit from nature's unasked for experiments, which are encountered by his medical colleagues in their clinical material. There are many examples of subjects of study - for instance hemoglobins and immunoglobulins - which started in a medical context and gradually developed into a field of prime interest for the molecular biologist. The study of blood coagulation is one of the younger areas of this kind.

This book has been written from two points of view: firstly, from the viewpoint of those who are involved in the diagnosis and treatment of lymphoid malignancies, who must meet the challenge of integrating the new biological insights into their knowledge of these diseases; and secondly, from the viewpoint of those who are involved in basic biological approaches to malignancy and immunology, who wish to know more about the function of the lymphoid tissues and their malignant diseases. Neoplasia of lymphocytes is a focus for considering many of the most important biological advances impinging on cancer in the past two or three decades, because malignant lymphoproliferative diseases offer unequalled opportunities for studying many aspects of cancer. We probably know more about lymphocytes than other normal cells because of the ease with which they can be obtained. For the same reason we probably know more about malignant lymphocytes. One or other aspect of most of the momentous advances in biology of the past two or three decades has implications for lymphoid malignancies: hybridoma technology and the use of monoclonal antibodies, gene technology, the understanding of oncogenes and growth factors in the control of growth and differentiation, insights into causation of cancer by potent tumour promoters such as the phorbol esters and by viruses, and knowledge of the control of growth function of lymphocytes themselves. Conversely, many of the advances in understanding lym phocytic leukaemias and lymphomas have implications for other cancers."

I am honored to be invited to prepare a foreword for the proceedings of the Second International Lubeck Conference on Erythropoietin (Epo). I congratulate Wolfgang Jelkmann, Horst Pagel and Christoph Weiss for their organization of an excellent program for this conference which updated all of us on the advances made in erythropoietin research during the past few years since the first conference in June of 1988. I am sure that Professor Paul Carnot, had he been present at this conference, would be very pleased and proud of the advances made in the field of erythropoietin since his and Madame DeFlandre's seminal finding in 1906 (1) that rabbits produced a humoral substance following bleeding which controls red blood cell production. The reports by Hjort in 1936 (2) and by Erslev in 1953 (3) that large volumes of plasma or serum from rabbits following a bleeding stimulus, when injected into normal donor rabbits, produced a reticulocytosis, were very significant in confirming the existence of a humoral factor which controls erythropoiesis. Reissmann's parabiotic rat experiments in 1950 (4) reawakened interest in erythropoietin when he proved that hypoxia stimulated the production of a factor which regulates red cell produc tion. The studies of several investigators such as Jacobson et al. (5), Fisher and Birdwell (6), Kuratowska et al. (7) and Nathan et al."

Knowledge of mechanisms involved in the pathogenesis of occlusive arterial dis eases is fundamental for the design of prevention and treatment. A series of studies based on in vitro investigations, the experimental animal and the human being have slowly increased our understanding of cardiovascular diseases and unveiled their secrets to us. Over the last 60 years it has been generally assumed that dietary fats and lipids and the occurrence of atherosclerosis are closely related. Yet, even if epidemiological studies clearly indicate the existence of an association between the amount of composition of dietary lipids and morbidity and mortality of cardio vascular disease, our basic knowledge on cause and effect is still hidden in a cloud of uncertainty. The present book discusses the relation between dietary lipids and arterial throm bosis, which latter process has been observed in the coronary arteries in up to 90% of subjects with acute myocardial infaction. In this volume Dr. Hornstra, who has occupied himself with thrombosis research with never-failing enthusiasm, great skill and critical approach for the last fifteen years, tries to establish possible links between lipid metabolism and thrombosis. His literature studies are comprehensive and his investigations are impressive in that they give a new dimension and a new methodology to research of lipids and thrombosis."

xi List of first authors xiii Acknowledgements xv INTRODUCTICN Approaches to radiolabelling blood d-c cells: past, present and future M. L. Thakur 3 CELL LABELLllJG TEDlNIQUES 2 Labelling techniques of granulocytes and platelets 17 with 111 In-oxinate M. R. Hardeman, E. G. J. Eitjes-van Overbeek, A. J. M. van Velzen, M. H. Rovekarnp 111rndium-labelling of human washed platelets; kinetics 3 29 and in vivo sequestration sites M. Eber, J. P. Cazenave, J. C. Grob, J. Abecassis, G. !o1ethlin 111Indium loss from platelets by in vitro and ex 4 44 vivo manipulation R. J. Hawker, C. E. Hall, H. C-oldman, C. N. McCollum PIATELEl'S: KrnETIC STUDIES 5 The maturation of megakaryocytes and their precursors 65 J. H. Paulus 6 !o1egakaryocytic precursors 74 J. Breton-Gorius, W. Vainchenker 7 !-1ethods of quantification of platelet production 86 in man. A critical analysis Y. Najean vi 8 Platelet production rate deteDmination with (75se)_ seleno-m:thionine R. Cardinaud, E. Dassin 96 9 Platelet kinetics: the state of the art A. duP Heyns 110 10 Platelet kinetics A. M. Peters 130 Evaluation of models to deteDmine platelet life 11 span and survival curve shape M. G. LOtter, C. P. Herbst, P. N. Badenhorst, A. duP Heyns, P. Wessels, P. C. Minnaar 139 12 Canparison of three m:thods evaluating platelet survival tim: in patients with prosthetic heart valve J. Schbath, D. Ville, B. Hathy, B. Sanchini, E. Benveniste, J. Belleville, M. Dechavanne, J. P. Boissel, J.

United States government. Defense Nuclear firms, Hoffman-LaRoche and Ciba-Geigy, and by Agency, Armed Forces Radiobiology Research In- the American firm, Travenol. stitute. SIEGMUNDJ. BAUM Furthermore, we greatly appreciate the gener- G. DAVID LEDNEY ous financial support by the Swiss pharmaceutical vi Xlll List of Contributors Part I Regulation of Stem Cell Proliferation L. G. Lajtha 1 Regulation of Stem Cell Proliferation 3 L. G. Lajtha and E. G. Wright Introduction 3 Experimental Evidence 3 Summary 7 References 7 Contents 2 Surface Antigens of Hemopoietic Stem Cells: The Expression of BAS, Thy-1, and H-2 Antigens on CFU-s 9 Ger van den Engh, Jim Russell, and Diane de Cicco Introduction 9 Materials and Methods 10 Results 11 Discussion 13 Summary 14 Acknowledgments 14 References 15 3 The Regulation of Hemopoiesis: Effect of Thymosin or Thymocytes in a Diffusion Chamber 17 S. J. Sharkis, A. Ahmed, L. L. Sensenbrenner, W. W. Jedrzejczak, A. L. Goldstein, and K. W. Sell Introduction 17 Materials and Methods 17 Results 18 Discussion 20 Summary 21 Acknowledgments 21 References 21 4 Anti-CFU-s Activity of Rabbit Anti- mouse Brain Serum: Mechanism of Action 23 Solomon S. Adler, Richard D. Kuznetsky, and Frank E. Trobaugh, Jr. Introduction 23 Materials and Methods 23 Results 26 Discussion 29 Summary 31 Acknowledgments 31 References 31 vii Contents Part II Ralph van Furth, Theo J. L. M. Goud, and Physiology of Committed Dick van Waarde Stem Cells 33 Introduction 65 D.

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

This volume contains papers presented at a symposium on "The Role of Lympho cytes and Macrophages in the Immunological Response" at the XIII International Congress of Haematology, Munich, August 1970. This symposium was designed to highlight current work submitted to the Haemato logy Congress which related to the role of cellular cooperation in induction and expression of the immune response. The symposium was divided into two parts. The morning session consisted of invited papers dealing with various general aspects of the field (papers 1 to 5) which were relevant to the afternoon session, which con sisted of free communications submitted to the Congress. In the discussion it was emphasized that whereas lymphocyte activIty ultimately underlies all immune induction, the cellular and humoral manifestations of the immune response are governed by distinct yet interacting compartments of the ly.mphoid system. Much interest centred on the role of thymus-derived lymphocytes as cooperator cells in antibody formation; and the mechanisms by which macro phages assist antibody production. The discussion brought together work on lympho cyte activation, the generation of lymphocyte activation products (lymphokine factors) and the cellular events underlying the induction and expression of the Immune response. The helpful cooperation of Springer-Verlag has enabled rapid publication of the papers presented at this symposium. London, February 1971 D. C. DUMONDE Symposium Moderator Contents The Spectrum of Thymus Dependency. E. LEUCHARS 1 The Flow of Information during Primary Antibody Synthesis. D. ]ACHERTS."

G. F. FUEGER Among the many processes in Physiology few appear mo e inviting to be studied by tracers and external imaging than the variety of the routes of migratory (blood) cells in health and disease. Much emphasis has been placed lately on the methods of labelling of the white blood cells. It is obviously quite important and necessary to refine the methods of leucocytic labelling, particularly to search for ways to label selectively a specific group of white blood cells, but there is also the need to review and keep abreast with the developing knowledge of the white blood cells themselves, especially their behaviour under pathological conditions, as seen by histology and scintigraphy, their biological properties, their immunological characteristics and the mechanisms of the control of leucocytic functions. Similarly, it appears desirable to analyze animal models of inflammation as well as to review the dosimetry and the biodistribution of labelled white blood cells in humans. This book is the result of a cooperative effort to review certain highlights of the physiology of leucocytes, labelled and unlabelled, as a corollary to the effort concerning the labelling of white blood cells. In preparing this book we aim for a better understanding and definition of the goals to be achieved by the successful labelling of the migratory cells of the body. XI CONTRIBUTORS Becker, H. Medizinische Universitaetsklinik der Uni versitaet Graz, Graz, Landeskrankenhaus, haus, Austria Bjurman, B. Department of Radiation Physics, General Hospital, Malmoe, Sweden Chiles, C."

The practice of transfusing blood started at the bedside but over the last few decades blood transfusion has become more and more a laboratory directed discipline. The emphasis on serology and laboratory controlled measures has made blood transfusion safer and more effective, but laboratory and clinical aspects of the discipline have tended to become increasingly separated. As a result of this separation clinical developments in blood transfusion may not have derived full benefit from the knowledge accrued in blood transfusion services. Over the last five years the Red Cross Blood Bank Groningen-Drenthe has organised yearly symposia with a clinical theme in order to bring blood banks and clinicians closer together. Many of the recent major advances in clinical medicine have been based on developments in blood transfusion practice. This is certainly true for paediatric medicine. For instance, in paediatric oncology, including leukemia, cell separator programmes have made available new forms of support. Further, blood component therapy has provided an effective means of control in some of the bleeding disorders of children. Some of these topics are discussed in this symposium dealing with intensive care. Haemolytic disease of the newborn and exchange transfusion are other aspec.ts of intensive care. Our purpose in dealing with them was twofold.

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."