bluuebunny/crossref_metadata_2025 huggingface dataset:
Intact Megakaryocytes in the Venous Blood as a Marker for Thrombopoiesis
Authors: Pedersen N. Tinggaard , Cohn J.
Published: August 2010

A total of 110 children, aged 0–15 years, were investigated for circulating megakaryocytes in cubital venous blood using the saponin‐haemolysis leucoconcentration technique. The average number of megakaryocytes decreased from 17.8 per ml blood in the first year of life to 5.5 after the 6th year, which is the same value as in adult humans. The intact thrombo‐cytogenic megakaryocyte value decreases from about 40 % in the first year of life to only a few percent (< 5 %) after the 10th year, the same value as in adult humans. There was a significantly higher number of megakaryocytes in children aged 0–6 years than in those aged 7–15 years. We concluded that occurrence of intact megakaryocytes ≥ 25 % in the venous blood is a sign of a normal thrombopoietic activity in the bone marrow, and the percentage of intact megakaryocytes in cubital venous blood reflects the decrease in thrombopoiesis in the bone marrow of fingers, hands and forearms during childhood. The decline in thrombopoietic activity is concentrated in three periods: 1–3, 6–7 and 10–11 years. An occurrence of intact megakaryocytes > 5 % in venous blood draining organs or bone marrow is a sign of some thrombopoietic activity.
Subclassification in Acute Lymphoblastic Leukaemia: Acid Phosphatase Reaction and Immunological Markers in Relation to Clinical Features
Authors: Boesen Anne Marie , Ellegaard Jørgen , Hokland Peter , Lassen Lissi Bank
Published: August 2010

A prospective, comparative study of cytochemical and immunological markers and clinical features was undertaken in 44 patients with ALL (children and adults). 12 patients (27%) had T‐ALL, 1 patient (2%) B‐ALL and 31 patients (71%) (non‐T, non‐B)‐ALL. E‐rosetting lymphoblasts ranged from 35 to 96% (median: 61), highest when AET‐treated SRBC were used as indicator cells. All 12 E‐rosette positive cases were strongly acid phosphatase (AcP)‐positive, showing a homogeneous pattern of distinct granular AcP‐activity in more than 85 % of the lymphoblasts (median: 96 %) significantly different from the median of 26 % granulated blasts found in the (non‐T, non‐B)‐ALL cases. Counting blasts with granular AcP‐activity proved to be both easier than using a scoring system for the AcP‐reaction and more efficient in terms of discriminating ability between the subgroups. Significant clinical and haematological features characterizing the T‐ and AcP‐positive cases included: (1) Predominance of young adult men, (2) presence of a mediastinal mass, (3) involvement of skin and serous membranes, (4) only slightly affected haemoglobin concentration at presentation, (5) difficulty in obtaining complete remission, (6) shorter duration of first complete remission and (7) shorter survival rate. It is confirmed that AcP‐staining of lymphoblasts is an easy, reproducible and inexpensive method for identifying the T‐cell variety of ALL.
Erythrocyte 2,3‐Diphosphoglycerate and Adenosine Triphosphate in Polycythaemia Vera
Authors: Monti M.
Published: August 2010

Erythrocyte 2,3‐diphosphoglycerate (2,3‐DPG) and adenosine triphosphate (ATP) were measured in 16 patients with polycythaemia vera and found to be normal.

The determination of erythrocyte organic phosphate concentration can be helpful in the differential diagnosis of different types of polycythaemia due to the lack of 2,3‐DPG rise in patients with polycythaemia vera, as compared to the 2,3‐DPG increase usually observed in patients with secondary polycythaemia.
Glucocorticoid Receptors in Human Polymorphonuclear and Mononuclear Leucocytes
Authors: Kontula K. , Myllylä G. , Andersson Leif C.
Published: August 2010

Both polymorphonuclear (PMN) and mononuclear (MN) leucocytes constitute targets for glucocorticoid hormones. In order to comparatively characterize the earliest steps of steroid action in these cell populations, we investigated the concentrations and specificities of glucocorticoid receptors in purified human PMNs and MNs by a whole‐cell binding assay using (3H)dexamethasone as the ligand. PMNs and MNs were found to contain the same amounts of glucocorticoid receptors (4720 and 4900 receptor sites/cell, respectively). The equilibrium dissociation constant (Kd) of the interaction between the cellular receptor and (3H)dexamethasone was about the same (1 times 10‐8 M) in both cell populations. No significant differences in the specificities of the steroid binding sites in PMNs and MNs were found; competition studies revealed the following order of relative binding affinities for a number of compounds: betamethasone > dexamethasone > prednisolone > cortisol > deoxycortico‐sterone = progesterone > aldosterone > testosterone > estradiol‐17β. We conclude that known differences in the sensitivities of PMNs and MNs to glucocorticoids are apparently not caused by differences in the concentrations or characteristics of their glucocorticoid receptors.
Iron Absorption in Relation to Iron Status
Authors: Magnusson B. , Bjorn‐Rasmussen E. , Hallberg L. , Rossander L.
Published: August 2010

The absorption from a 3 mg dose of ferrous iron was measured in 250 male subjects. The absorption was related to the log concentration of serum ferritin in 186 subjects of whom 99 were regular blood donors (r = —0.76), and to bone marrow haemosiderin grading in 52 subjects with varying iron status. The purpose was to try and establish a percentage absorption from such a dose that is representative of subjects who are borderline iron deficient. This information is necessary for food iron absorption studies in order (1) to calculate the absorption of iron from the diet at a given iron status and (2) compare the absorption of iron from different meals studied in different groups of subjects by different investigators. The results suggest that an absorption of about 40 % of a 3 mg reference dose of ferrous iron is given in a fasting state, roughly corresponds to the absorption in borderline‐iron‐deficient subjects. The results indicate that this 40% absorption value corresponds to a serum ferritin level of 30 μg/1 and that food iron absorption in a group of subjects should be expressed preferably as the absorption corresponding to a reference‐dose absorption of 40 %, or possibly a serum ferritin level of 30 μg/1.
Mobilisation of Iron from Peritoneal Rat Macrophages by Desferrioxamine
Authors: Kleber E. E. , Torrance J. D. , Bothwell T. H. , Simon M. O. , Charlton R. W.
Published: August 2010

The amount of radioiron released from rat peritoneal macrophages after phagocytosis of 59Fe labelled erythrocytes can be enhanced by addition of desferrioxamine. The effect is dose dependent and the iron chelated by desferrioxamine appears to be at the expense of ferritin. However, desferrioxamine does not appear to chelate iron already incorporated into ferritin. It seems likely that the iron comes from a labile chelatable pool through which the iron from haemoglobin catabolism passes before being incorporated into ferritin. The desferrioxamine appears to enter the macrophage and chelate iron to form ferrioxamine which subsequently leaves the macrophage. In vivo it was not possible to show substantial iron chelaton by desferrioxamine in rats when 59Fe labelled non‐viable red cells were injected intravenously. This suggests that in vivo mobilization of reticuloendothelial iron by desferrioxamine may be of limited significance.
Haematological and Haemopoietic Studies in an Air‐Breathing Fish on Cyanocobalamin and Folacin Deficient Diet
Authors: Mahajan C. L. , John M. J.
Published: August 2010

Experimental deficiencies of cyanocobalamin and folacin separately and in combination were induced in an air‐breathing teleost fish Channa punctatus with the help of a complete vitamin test diet. Cyanocobalamin deficiency produced normocytic hypochromic anaemia while the folacin deficiency as well as the combined deficiency of both vitamins produced macrocytic hypochromic anaemia. Leucocytosis was observed in the individual and combined deficiencies of these vitamins with significant increase in thrombocytes and decrease in neutrophil population. The relative population of different developing stages in erythropoiesis showed significant change. Thus small lymphoid haemoblast decreased in number while young and mature reticulocyte populations increased. Recovery to normal condition could be obtained by restoring deficient groups of fishes to complete vitamin test diet fortified with an initial i.m. administration of 0.01 mg/g and 0.02 mg/g body wt. of cyanocobalamin and folacin respectively. A comparison of deficiency effects on C. punctatus with Labeo rohita shows that the former, a carnivorous species with higher Hb content in peripheral blood is more susceptible to deficiency than the latter, a herbivorous species of fish with lower Hb values.
Granulocyte Function in Children with Acute Lymphoblastic Leukaemia During Remission
Authors: Heilmann Carsten , Pedersen Freddy Karup
Published: August 2010

The granulocyte function of 20 children with acute lymphoblastic leukaemia was studied during remission and compaired to that of 20 healthy adults. Granulocyte function was equally decreased when examined in patient serum and pooled normal serum. The decreased bactericidal function was predominantly due to reduced intracellular killing. Patients with grossly reduced granulocytic function had more infections than the rest of the group, though the difference was not statistically significant.
Radiotherapy versus Radiotherapy plus Chemotherapy in Stages I and II Hodgkin's Disease.
Authors: Nissen Nis I. , Nordentoft A. M. , Brincker H. , Andersen E. , Jensen M. Krogh , Nielsen J. Boye , Pedersen‐Bjergaard J. , Jensen T. Skov , Jensen K. Bjørn , Videbæ Aa. , Pedersen M. , Walbom‐Jørgensen S.
Published: August 2010

In a multi‐centre study in which data from all Danish Hodgkin patients have been registered since 1971, all patients in supradiaphragmatic stages I or II, as confirmed by staging laparotomy, were randomized to either radiotherapy (RT) to supra‐ and infradiaphragmatic lymph node regions (total nodal irradiation, TNI), or RT to a mantle field followed by 6 cycles of MOPP combination chemotherapy (RT+ CT).

Interim results up to July 1979, when 237 patients had entered the study, showed a treatment failure rate of 19/117 in the TNI group and 4/120 in the RT+CT group (P < 0.05). 19 of the 23 relapsing patients were under the age of 40, and 14 in the TNI group and 3 in the RT+CT group belonged to stage II. 13 patients had nodular sclerosis, 9 had mixed cellularity and 1 had lymphocytic predominance histology. 12 of the 19 relapsing patients in the TNI group had hilar or mediastinal involvement as against 51 of the 117 patients in the entire group. Most of the TNI failures could be retreated, and as yet there is no difference in the overall survival.
Inhibitory Ability of Adherent Blood Cells from Patients with Chronic Myeloid Leukaemia on DNA‐Synthesis in Non‐Adherent Leukaemic Cells and PHA‐Stimulated Lymhpocytes
Authors: Unsgaard Geirmund , Lamvik Jon O.
Published: August 2010

Mononuclear blood cells were isolated from patients with different types of leukaemia and studied in vitro with regard to cell functions – adhesiveness, phagocytosis, DNA synthesis and inhibitory effects of adherent cells on non‐adherent leukaemic cells and PHA stimulated lymphocytes.

Cells from patients with chronic myeloid leukaemia (CML) adhered to the plastic surface of the culture dishes and showed esterase staining reactions as monocytes/macrophages. They showed a normal capacity to ingest Candida albicans, while the digestion capacity appeared reduced.

Non‐adherent cells from CML showed a high ability to incorporate thymidine, indicating DNA synthesis. Adhesive cells from patients with CML inhibited DNA synthesis in non‐adherent CML cells and in PHA‐stimulated lymphocytes to about the same extent as adhesive cells from normal donors.

Blood cells from acute myeloid leukaemia and chronic lymphocytic leukaemia showed no adhesiveness and a very low spontaneous thymidine incorporation.
In Vitro Colony and Cluster Growth in Haemopoietic Dysplasia (The Preleukaemic Syndrome).
Authors: Lidbeck Jan
Published: August 2010

The growth and differentiation of granulopoietic progenitor cells from 15 patients with haemopoietic dysplasia were studied by in vitro culture in agar‐gel. After 14 d in culture whole colonies and clusters were transferred to glass slides and were stained with a modified Papanicolaou technique. The preparations were examined for cellular differentiation by counting the number of mature cells (band forms and polymorphonuclear cells) and a mitotic index was calculated from the number of mitotic cells. Patients with defective colony formation showed granulopoietic maturation defects and a reduced mitotic index was found in some colonies. Patients who had colony counts within the normal range, however, showed normal in vitro maturation.

Defective colony growth in haemopoietic dysplasia generally indicates a malignant course and can occasionally be related to leukaemic transformation. The finding of in vitro maturation defects is an additional culture abnormality which may indicate a deteriorating clinical course. A defective maturation and a reduced mitotic index in vitro add support to the concept of clonal progression in malignant haemopoietic dysplasia.
The Concentration of Vitamin B12, Transcobalamins and Folate in Blood in a Greenland Eskimo Population Sample.
Authors: Hansen Peder Kern , Fenger Hans Jørgen , Gimsing Peter , Gudmand‐Høyer Eivind , Hippe Erik
Published: August 2010

The concentrations of cobalamin and transcobalamin I and II in plasma and of folate in erythrocytes were determined in a Greenlander population sample. Compared with the Danish reference group, cobalamin and transcobalamin II were increased in the Eskimos, whereas there were no differences in transcobalamin I and erythrocyte folate.
Antibody‐Dependent Monocyte‐Mediated Cytotoxicity.
Authors: Kragballe Knud , Ellegaard Jørgen
Published: August 2010

Antibody‐dependent cytotoxicity mediated by purified monocytes was determined in 42 patients suffering from acute myeloid leukaemia (AML). Compared to 9 patients with acute bacterial infection and to 42 normal controls, patients with untreated AML exhibited deeply depressed monocyte cytotoxicity. Cytotoxicity was reduced in each of the cytomorphological subgroups of AML. Patients attaining remission showed the same cytotoxicity as patients not attaining remission. During remission monocyte cytotoxicity increased significantly, but normal function was not achieved. Patients receiving chemotherapy alone exhibited the same defective cytotoxicity as patients receiving chemotherapy plus immunotherapy with Coryne‐bacterium parvum. The termination of maintenance chemotherapy after remission for 1 year did not normalize cytotoxicity. Also the cytotoxicity of normal monocytes was not affected by patient serum.

It is suggested that the reduced monocyte cytotoxicity observed in AML is related to the leukaemic process. The lack of complete normalization during the remission may indicate the continuous presence of an intrinsic defect of monocytopoiesis.
Platelets in Myeloproliferative Disorders
Authors: Boneu B. , Nouvel C. , Sie P. , Caranobe C. , Combes D. , Laurent G. , Pris J. , Bierme R.
Published: August 2010

Certain platelet functions were evaluated in 24 patients with secondary polycythaemia (SP) and in a large number of patients suffering from myeloproliferative disorders (MD'S): 89 patients with chronic myeloid leukaemia (CML) at different stages of development, 58 with polycythaemia vera (PV), 23 with essential thrombocythaemia (ET), and 25 with agnogenic myeloid metaplasia (AMM). Bleeding time, epinephrine‐induced platelet aggregation and adhesiveness agree with those generally reported in the literature; they are independent of thrombocytosis, the haemoglobin level and the leucocyte count. Macrothrombocytosis, evaluated by an electronic method, was only found in CML, mainly during acute blast crisis. An increased percentage of light platelets was a constant feature in all groups except in the SP and in 20 % of the PV. The most severe abnormalities were observed in AMM and CML in the acute stage; in the chronic phase of CML there is no correlation between the severity of platelet abnormalities and the survival of the patients.
Deoxyuridine‐Suppression Test and Bone Marrow Culture for the Diagnosis of Macrocytic Refractory Anaemias
Authors: Garand R. , Zittoun J. , Marquet J. , Mouraud E. , Grolleau J. Y. , Le Mevel A. , Zittoun R.
Published: August 2010

Deoxyuridine (dU) suppression test and granulocyte macrophage colony forming unit (CFU‐GM) assay were performed, along with morphological analysis, vitamin B12 and folate assays, in 22 cases of macrocytic anaemia corresponding to various types of idiopathic dysmyelopoietic syndromes. The dU suppressive effect was found to be normal in 19 cases, and slightly subnormal in 3 cases. The parallel study of the in vitro bone marrow growth showed, except in cases of primary acquired sideroblastic anaemia, a reduced number of colonies associated with a relative increase of the cluster formation. Consequently, these two parallel functional studies can support a formal diagnosis of potentially preleukaemic myelodysplasia, whatever may be the morphological pattern and even in cases of marked macrocytic anaemias and secondary epiphenomenal folate or vitamin B12 deficiency.
Chronic Lymphocytic Leukaemia and IgG Heavy Chain Disease
Authors: Briët E. , van Nieuwkoop J. A. , v.d. Zijde C. M. Jol‐ , den Ottolander G. J. , Rádl J.
Published: August 2010

A 64‐year‐old woman who has suffered from chronic lymphocytic leukaemia since 1976 is discussed. In 1978, an abnormal protein component was found in her serum by means of immunoelectrophoresis. Using the techniques of immunoselection of the serum immuno‐globulins and immunofluorescence of the bone marrow cells, it was demonstrated that this component consists of IgG1 heavy chains only. The native protein, COL, consisted of a dimer linked by disulphide bonds of a molecular weight of 80000 daltons. Its monomeric unit had a molecular weight of 40000 daltons, as determined by SDS‐polyacrylamide gel electrophoresis after reduction with 2‐mercaptoethanol. Protein COL was not produced by the leukaemic cells (which bore IgM‐γ on their membrane) but by a morphologically distinct clone of lymphoid cells. After therapy with chlorambucil, the level of the heavy chain disease protein in the serum decreased substantially.
Localized Blastoma Preceding Blastic Transformation in Ph1‐Positive Chronic Myelogenous Leukaemia: Morphological and Cultural Studies of the Transformation Event
Authors: Asano S. , Sato N. , Ueyama Y. , Mori M. , Sakurai M. , Tamaoki K. , Chiba S. , Imamura Y. , Kosaka K.
Published: August 2010

In a patient with Ph1‐positive chronic myelogenous leukaemia (CML), the development of a localized blastoma preceding generalized blastic transformation was accompanied by a reduction of granulocyte‐macrophage (GM) colony forming capacity in agar of bone marrow cells as well as an increase in peripheral neutrophil alkaline phosphatase (NAP) scores. Successful transplantation of the blastoma cells into nude mice enabled extensive studies of the cell properties. The blastoma cells were double Ph1‐positive cells which did not respond to human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and were similar to cells demonstrated in spleen and bone marrow at the terminal stage of the patient's illness. These observations clearly support the case for sequential studies of colony formation in vitro as a useful test for the early detection of disturbances in marrow function that may occur before generalized blastic transformation. Studies of the properties of the blastoma cells also provide some insight into possible mechanisms for the transformation event.
Serum Beta2‐Microglobulin in Acute and Chronic Leukaemia
Authors: Ellegaard Jørgen , Mogensen Carl Erik , Kragballe Knud
Published: August 2010

The serum concentration of beta2‐microglobulin (beta2‐m) was measured in 69 patients with acute or chronic lympho‐ and myeloproliferative disorders. Serum beta2‐m was found significantly increased in 12 out of 14 patients with chronic lymphatic leukaemia. The serum concentration was proportional to the estimated lymphatic infiltration of tissues but inversely related to the number of circulating lymphocytes. Cytostatic treatment was followed by a decrease in serum beta2‐m, but normalization of the serum concentration was not observed. 11 patients with chronic granulocytic leukaemia all had significantly elevated serum concentrations of beta2‐m and increased serum concentrations were also found in patients with acute leukaemias. Thus, 12 out of 25 patients with acute myeloid leukaemia and all of 5 patients with acute myelomonocytic leukaemia as well as 4 out of 5 patients with acute lymphatic leukaemia had increased serum beta2‐m levels. In acute leukaemia no correlation could be demonstrated between the blood lymphocyte concentration and serum beta2‐m. Also no significant changes in serum beta2‐m were found in either remission or relapse of the acute leukaemia. It is concluded that serum beta2‐m in patients with chronic leukaemia may reflect the total amount or turn‐over of leukaemic cells in the body and that repeated determinations of serum beta2‐m in these patients might be useful as an estimate of the residual leukaemic cell mass after therapy. Apart from this the determination of serum beta2‐m seems to be of little, if any, clinical use in leukaemia.
The Volume of the Human Erythrocyte and Plasma Alkaline Phosphatase Activity
Authors: Lovlin R. E. , Kinnear G. , Sewchand L. S. , Rowlands S.
Published: August 2010

Changes in mean red cell count (RCC), mean cell volume (MCV) and plasma alkaline phosphatase activity (ALP) were observed in a group of 33 normal male university students at a 7‐week interval. Linear regression analysis shows a negative linear relationship between changes in RCC and MCV (r = ‐0.77, P < 0.0005) while a positive correlation was found for changes both in ALP activity and in MCV (r = +0.37, P < 0.025). Multiple regression analysis indicates that 70% of the variation in MCV could be accounted for by changes in RCC and plasma ALP activity (r = +0.84, P < 0.0025).
Elevated Hb F Associated with β‐Thalassaemia Trait: Haemoglobin Synthesis in Reticulocytes and in Blood BFU‐E
Authors: Dubart A. , Testa U. , Musumeci S. , Vainchenker W. , Beuzard Y. , Henri A. , Schirilo G. , Romeo M. A. , Russo G. , Rochant H. , Rosa J.
Published: August 2010

The red cells of a patient heterozygous for β‐thalassaemia contained 19% fetal Hb. Study of his family suggested that the proband had inherited the Swiss type of hereditary persistence of fetal Hb (HPFH) from his mother who is not thalassaemic and possessed 1.37% of Hb and 11% F‐cells. Studies of globin synthesis showed a similar imbalance in the heterocellular HPFH‐β‐thalassaemia compound heterozygotes and in the heterozygous β‐thalassaemic members of the family. Age stratification of the red cells showed a slight enrichment in Hb F and a decreased Hb A2 level in the older cell populations. Hb F production in the BFU‐E colonies of the proband was higher than that found in vivo and in other β‐thalassaemic heterozygotes in culture. Study of single erythroid burst colonies showed a marked heterogeneity in Hb F synthesis from one colony to another, while the pool of free α‐chains remained of similar magnitude. It is suggested that in the proband, the HPFH gene, which is in trans with respect to the β‐thal‐gene, increases the size of the F‐cell population and its activity is carried on at the expense of the normal βA gene.
Erythrocytotoxicity Induced by Cancer Chemotherapeutic Agents
Authors: Barr Ronald D. , Davidson Alan R. , Jung Lawrence K. L. , Pai K. R. Mohan
Published: August 2010

Increased osmotic fragility and methaemoglobin generation in vitro have resulted from the exposure of normal human erythrocytes to numerous cancer chemotherapeutic agents. These findings offer a possible explanation for the earlier, consistent clinical observation of the rapid development of anaemia, during consolidation therapy, in children with acute lymphoblastic leukaemia in remission.
The Euglobulin Clot Lysis Time, a Rapid and Sensitive Method for the Assay of Fibrinolytic Activity after Venous Stasis
Authors: Nordby E. , Arnesen H. , Andersen P. , Godal H. C.
Published: August 2010

For the estimation of fibrinolytic activity in euglobulin precipitates after venous stasis, the euglobulin clot lysis time (ECLT) proved to be as reproducible and probably even more sensitive than the fibrin plate method (FP). Furthermore, when euglobulin precipitates from 55 healthy individuals and 36 patients with thromboembolic disease were examined, a good correlation between the two methods was observed. The present observations indicate that the ECLT is suitable for routine screening of fibrinolytic activity after venous stasis.
CRITICAL POINTS IN SECONDARY MYOCARDIAL INFARCTION TRIALS
Authors: CORTELLARO M.
Published: August 2010

In the Anturan Reinfarction Italian Study (ARIS) some specific and quantitative hemostatic parameters are being investigated at different times and in different series of patients balanced for sulfinpyrazone (S) and placebo (P) in order to ascertain if one or more of these parameters may be considered as forecasting elements. A series of 186 myocardial infarction (m. i.) patients was randomly allocated to S and P 15–25 days after the m.i. episode, and tests performed at treatment allocation and after 1, 6 and 12 months. In comparison with 44 healthy volunteers, the results have provided striking confirmation of “hyperactive” platelets in the early phase of m.i.: the bleeding time (BT) was shorter, β‐thromboglobulin (β‐TG) increased, PF4release increased, heparin thrombin clotting time (HTCT) shorter, and platelet sensitivity to threshold concentrations of ADP and collagen increased. Significant changes in BT, P F4release and HTCT persisted at successive testing times. Platelet aggregation by low collagen concentrations was inhibited in the S subsample patients.

In a different series of young male patients who had had a m.i. 6 months previously, it has been shown that the P treatment subsample presented shortened platelet production time (PPT), increased levels of plasma ‐TG and PF4and increased factor VIII:RAg compared with a matched control group. The S treatment subsample presented normalized PPT accompanied by reduction of VIlhRAg but not of β‐TG or PF4. plasma levels. It will be possible to evaluate the prognostic significance of these results only when the above pattern in the parameters can be correlated with the major and minor clinical events observed in patient follow‐up, that is, after ARIS closes.

Prospective clinical trials with platelet anti‐aggregating agents were started when it was realized that for such drugs to be defined as anti‐thrombotic it was not sufficient to show that they had an effect on platelet functionin vitroorex vivo, and only the demonstration that they are efficacious in preventing specific clinical endpoints would justify defining them as antithrombotic.
Histiocytic Medullary Reticulosis Complicating Chronic Lymphocytic Leukaemia: Malignant or Reactive?
Authors: Manoharan A. , Catovsky D. , Lampert I. A. , Gordon‐Smith E. C. , Galton D. A. G. , ‐Mashadhani Al
Published: August 2010

We describe 4 patients with a haemophagocytic syndrome resembling histiocytic medullary reticulosis (HMR) complicating chronic lymphocytic leukaemia (CLL) of 9 months to 8 years duration. Surface marker studies in 2 cases showed that the CLL lymphocytes were of B‐cell type in one and of T‐cell type in the other. 2 of the patients had histological evidence of co‐existing immunoblastic sarcoma at the time of diagnosis of the HMR‐like syndrome and all 4 patients died within 3 weeks of this diagnosis.

The pathogenesis of the HMR‐like syndrome in these patients is discussed and it is concluded that it is probably reactive to an underlying opportunistic viral function related to their immunodepressed state secondary to CLL and/or the cytotoxic therapy.
Multiple Myeloma in Primary Biliary Cirrhosis
Authors: Blade Joan , Montserrat Emili , Bruguera Miquel , Aranalde Joan , Granena Albert , Cervantes Francesc , Rozman Ciril
Published: August 2010

A patient who had primary biliary cirrhosis and, simultaneously, multiple myeloma (IgG, lambda) is reported.

In chronic liver diseases, polyclonal hypergammaglobulinaemia is common, monoclonal gammopathies have also been found in rare instances, being attributed to chronic antigenic stimulation of the reticuloendothelial system by antigens from the intestinal flora. The mechanisms (as chronic antigenic stimulation, immunologic disturbances and granulomata formation) which apply to explain the development of monoclonal gammopathies in other conditions are also found in primary biliary cirrhosis. It is postulated that, in this disease, the development of multiple myeloma could be not merely coincidental but also the result of chronic stimulation of the reticuloendothelial system.
Surface Antigens on Normal and Leukaemic Human Cells Detected by Monoclonal Antibodies
Authors: Morstyn George , Metcalf Donald , Burgess Antony , Fabre John W.
Published: August 2010

Surface antigens were analyzed on normal human marrow and chronic myeloid leukaemic cells using 4 monoclonal mouse anti‐human antibodies. The fluorescence‐activated cell sorter was used to quantify the binding of each antibody to different subpopulations of cells, and sorted fractions were cultured in agar‐medium to assay for granulocyte‐macrophage and eosinophil precursors.

All cells in the granulocyte series including colony‐forming cells bound a similar quantity of an antibody to the human leucocyte common antigen. This antibody did not bind to cells in the erythroid series. A monoclonal antibody to antigen present on brain, lymphocytes and granulocytes (and almost certainly homologous to the W3/13 antigen of the rat) bound to the cells in the order: blast > promyelocytes and myelocytes > granulocytes. The third monoclonal antibody was directed against a determinant of the leucocyte common antigen present predominantly on B lymphocytes and absent from the myeloid series. The fourth antibody, directed against the human homologue of Thy‐1, reacted with less than 1% of marrow cells, none of which appeared to be granulocyte or eosinophil progenitors. The leucocyte common antigen and the brain‐lymphocyte‐granulocyte‐antigen were also present on colony‐ and cluster‐forming cells from a patient with chronic myeloid leukaemia. Using the low angle and wide angle light scatter properties of CML blood cells, 7‐fold enrichment was obtained for progenitor cells from chronic myeloid leukaemia. With the monoclonal antibodies up to 4‐fold enrichment was obtained.
Proliferation of Human Lymphoid Cells Lymphocytopoiesis and Cell Cycle Parameters in Isolated Perfused Human Spleens
Authors: Pabst R. , Reinecke G.
Published: August 2010

Parameters of the cell cycle of lymphoid cells and the rate of production of small lymphocytes and mature plasma cells were estimated in human spleens. 12 normal and 1 enlarged spleen with lymphatic hyperplasia were labelled either by a pulse or continuously with 3H‐TdR‐thymidine during normothermic perfusion of the isolated spleens. Biopsies of splenic tissue were taken at different intervals and evaluated autoradiographically. The mean initial labelling index of immunoblasts was 73% and for plasmoblasts 52%. The labelling index for small lymphocytes and mature plasma cells increased initially from 0 % to 1 %, and up to 25 % respectively after 14 h. The duration of the S‐phase, as determined by double labelling, was 8.26 h for lymphoid blasts. Data from the percentage labelled mitosis curve resulted in a minimal tG2 of about 1 h and tG2 + tM of about 4 h. The estimated generation time was about 11.5 h. The results found on the hyperplastic spleen were comparable to those on the normal spleen.
Platelet Function in Preleukaemia
Authors: Lintula R. , Rasi V. , Ikkala E. , Borgström G. H. , Vuopio P.
Published: August 2010

Platelet function was studied in 17 patients with preleukaemia and the results were compared with those of 28 patients with other chronic myeloproliferative disorders. The test pattern included bleeding time (Ivy), platelet retention (Hellem II), PF‐3 activity and availability after exposure to ADP and kaolin, and ADP‐, epinephrine‐, collagen‐ and ristocetin‐induced aggregations. Platelet function was frequently impaired in patients with preleukaemia. The defects were similar to those found in other myeloproliferative disorders. The most consistent finding was defective aggregation. Patients with thrombocytosis and/or with increased amounts of megakaryocytes in the bone marrow had fewer defects in platelet function. Retention defect was more common in patients with hypolobulated megakaryocytes, especially in those having a specific marker, the 5q‐ chromosome, in their bone marrow cells.
111Indium‐Chloride Bone Marrow Scintigraphy in Aplastic Anaemia
Authors: Pauwels E. K. J. , te Velde J. , Hermans J. , Haak H. L. , Jürgens Ph. J.
Published: August 2010

Bone marrow scintigraphy, using 111Indium‐chloride, was performed in 24 patients with acquired aplastic anaemia to investigate: (1) a possible relationship between bone marrow scintigraphy and peripheral blood cell values, (2) a possible relationship between scintigraphy and histology of the bone marrow and (3) the ability to distinguish various aplastic anaemia subtypes with bone marrow scintigraphy. For this purpose a semi‐quantitative scoring of scintigraphic results was used. Only a weak correlation was found between the radionuclide studies and blood counts. It appeared that an abnormal 111In‐scintigraphic activity in the pelvis was related to an abnormal quality and quantity of haematopoietic tissue. To study a correlation with histological subtype grading, the patients were grouped in 4 categories based on clinical‐histological results. Thus it could be demonstrated that the presence of 111In‐activity in long bones (‘scintigraphic extension’) is an important parameter in distinguishing patients who are believed to suffer from a primary stem‐cell defect, from patients who may suffer from an auto‐aggressive disorder.
Emperipolesis Observed in Immature Cells in Blast Crisis of Chronic Myelogenous Leukaemia
Authors: Ino Teruo , Hirano Masami , Shamoto Mikihiro
Published: August 2010

In a 62 year‐old male with chronic myelogenous leukaemia, an acute phase developed with appearance of large immature cells in the bone marrow. A significant proportion of these cells was found to have engulfed autologous immature and polymorphonuclear neutrophils, erythroblasts, red cells and platelets. These abnormal cells were Philadelphia chromosome positive, and considered to be derived from the leukaemic cell line. Electron microscopic examinations revealed, in the cytoplasm of engulfed cells, no lysosomes or phagosomes which are typically seen in phagocytic cells, nor any evidence of degenerative changes in either engulfing or engulfed cells. These findings suggest that this phenomenon be considered as emperipolesis rather than phagocytosis. The pathophysiological mechanism of this phenomenon is uncertain.
In Vivo Platelet Hyperactivity and Factor VIII Related Antigen Increase Long after Myocardial Infarction
Authors: Cortellaro M. , Boschetti C. , Beggi P. , Polli E. E.
Published: August 2010

In the Anturane Reinfarction Italian Study the trend of some specific and quantitative haemostatic parameters is being investigated in different series of patients balanced for sulfinpyrazone and placebo. In a series of young male patients who had had myocardial infarction 6 months previously, it has been shown that the placebo treatment subsample presented shortened platelet production time (PPT), increased levels of plasma β‐thrombo‐globulin (β‐TG) and platelet factor 4 (PF4), and increased factor VIII related antigen (VIII:RAg) compared with a matched control group. A close correlation between plasma concentration of VIILRAg and PPT was evidenced in the same treatment subsample. The sulfinpyrazone treatment subsample presented normalized PPT accompanied by reduction of VIII:RAg but not of β‐TG or PF4 levels.
Non‐Specific Iron in Patients with Beta‐Thalassaemia Trait and Chronic Active Hepatitis
Authors: Fargion Silvia , Cappellini M. Domenica , Sampietro Maurizio , Fiorelli Gemino
Published: August 2010

A non‐specific iron fraction, not bound to transferrin, has been looked for in the sera of 42 never‐transfused patients with beta‐thalassaemia trait, 17 of whom had chronic active hepatitis, negative for HBV infection or alcohol abuse. Non‐specific iron was found only in the sera of those patients with beta‐thalassaemia trait plus chronic active hepatitis who had complete transferrin saturation, high serum ferritin levels and urinary iron excretion and a high degree of hepatic siderosis. In view of the known toxicity of non‐transferrin iron, we suggest that this non‐transferrin iron fraction may be responsible for the liver damage in these patients.

Furthermore, the positive correlation between the presence and the amount of non‐transferrin iron and the levels of serum ferritin suggests that this fraction is a sensitive indicator of iron‐induced toxicity when severe iron overload slowly develops in patients with beta‐thalassaemia trait even in the absence of any iron administration.
Glutathione Peroxidase Activity in Whole Blood of Patients with Sickle Cell Anaemia
Authors: Zimmerman Carola Ponzetto , Natta Clayton
Published: August 2010

Whole blood glutathione peroxidase was found significantly increased relative to controls in a group of 21 black patients with sickle cell anaemia. One control group consisted of 15 normal black subjects. A second control group, consisting of 21 black patients with various abnormal haemoglobins including a‐thalassaemia, also showed a tendency to enhanced glutathione peroxidase activity, confirming previous reports that elevated glutathione peroxidase levels are secondary to a variety of haemolytic conditions, rather than typical of sickle cell anaemia.
Plasma Levels of Platelet Factor 4 in Patients Admitted to a Coronary Care Unit
Authors: Kutti Jack , Safai‐Kutti Soodabeh , Svärdsudd Kurt , Swedberg Karl , Wadenvik Hans
Published: August 2010

Blood was obtained from 63 consecutive patients within a 24 h period after the admission to a coronary care unit for the determination of plasma platelet factor 4 (PF‐4) concentration. 28 of the subjects proved to have an acute myocardial infarction (MI), 24 had evidence of ischaemic heart disease (IHD) but no MI, and the remaining 11 patients had no signs of IHD. 40 healthy subjects served as controls. The mean PF‐4 value in the MI group was 10.5 ±0.8 ng/ml. The corresponding values for patients with and without IHD were 8.7 ±0.6 and 8.3 ±0.6 ng/ml, respectively. The control mean (5.4 ±0.3 ng/ml) was significantly lower (P < 0.001) than the means for all 3 groups of patients studied. The difference between the group of MI patients and patients with IHD as well as patients without IHD was only of borderline significance (0.10 > P > 0.05).
Characterization of Glycophorin A and Band 3 from Tn Polyagglutinable Erythrocytes
Authors: Jokinen Mikko
Published: August 2010

The 2 types of erythrocytes from a person with persistent mixed‐field polyagglutinability (Tn abnormality) were separated from each other by preparative cell electrophoresis. Surface labelling using the galactose oxidase/NaB3H4 technique followed by polyacrylamide gel electrophoresis showed a strong labelling in the glycophorin A region of Tn positive erythrocytes indicating exposed galactosyl N‐acetyl/galactosaminyl residues. Tn positive cell membranes were labelled by the galactose oxidase/NaB3H4 technique and solubilized in non‐ionic detergent. After chromatography on Helix pomatia lectin‐linked Sepharose, glycophorin A was immunoprecipitated from the sugar eluate using specific antiserum. Glycophorin A from Tn negative cells and normal red blood cells did not bind to Helix pomatia lectin but to Lens culinaris lectin‐Sepharose. Glycophorin A and band 3 were isolated by preparative gel electrophoresis from normal cells and the two red cell populations of the Tn individual. Pronase treatment of labelled glycophorin A followed by gel filtration revealed a more efficient proteolysis in molecules isolated from Tn positive cells. Mild alkaline treatment of galactose oxidase/NaB3H4 or periodate/NaB3H4 labelled glycophorin A liberated 3 different oligosaccharides from Tn positive cells. No significant difference was found between the oligosaccharides of band 3 protein from normal and Tn positive cells and the amounts of glycophorin A were identical in both cell types when determined by radioimmunoassay.
Combination Chemotherapy for Marrow Relapse in Children and Adolescents with Acute Lymphocytic Leukaemia
Authors: Amadori Sergio , Antonietta Maria , Spiriti Aloe , Meloni Giovanna , Pacilli Leonardo , Papa Giuseppe , Mandelli Franco
Published: August 2010

38 children with acute lymphocytic leukaemia (ALL) in haematologic relapse were retreated with vincristine, daunomycin and prednisone (VPD) together with intrathecal methotrexate and prednisone, followed by asparaginase in those patients not in complete remission after 4 weeks. The overall complete remission (CR) rate was 79%; asparaginase was needed to achieve CR in 7 of the 30 responding patients. The median duration of second remission was only 36 weeks, but 6 out of 15 children receiving the COAP‐POMP‐CART consolidation regimen remain in continuous second remission after 37–260 weeks; 3 of them are currently off all therapy. It is concluded that a prolonged second remission can be achieved in children with ALL in bone marrow relapse by combining intensive chemotherapy with the prevention of meningeal leukaemia.
Positive Identification of Human Leukaemic Cells with Scanning Immuno‐Electron Microscopy, using Antibody Coated Polystyrene (Latex) Beads as Markers
Authors: Gamliel Haim , Polliack Aaron
Published: August 2010

Scanning immuno‐electron microscopic labelling techniques were successfully used to identify a variety of leukaemia‐lymphoma cells. Anti‐T, ‐B and ‐common type acute lymphoblastic leukaemia (ALL) antisera were covalently conjugated to polystyrene latex spheres by means of glutaraldehyde. Peripheral blood mononuclear cells obtained from healthy individuals and from patients with T‐type ALL, B‐type chronic lymphocytic leukaemia (CLL), acute and chronic non‐lymphoblastic leukaemias (ANLL) and cultured leukaemia‐lymphoma cells were incubated with the above antisera‐latex conjugates. Positively labelled cells were easily identified by the presence of latex spheres on their surfaces. Cross reactivity of the antisera used and non‐specific attachment of the markers were infrequently encountered. The results of this study confirm earlier scanning electron microscopic reports indicating that different leukaemic cells have characteristic surface features and show that scanning immuno‐electron microscopy (SIEM) can readily be applied to the study of human leukaemic cells.
The Prognostic Significance of in Vitro Bone Marrow Growth Pattern in Acute Non‐Lymphocytic Leukaemia
Authors: Gustavsson Anita , Olofsson Tor , Olsson Inge , Sigurdardottir Hrefna
Published: August 2010

The growth pattern of bone marrow cells in agar culture was studied in 56 patients with untreated acute non‐lymphocytic leukaemia. 4 different growth patterns were recognized: (A) colony and cluster formation, (B) growth of small clusters (3–20 cells) only but less than 600/105 cells, (C) growth of small clusters only but more than 600/105 cells, and (D) no growth in vitro. Patients in group A and B had a significantly higher remission rate (23/34) than patients in group C and D (3/22). This was true also when only patients below 60 years of age were considered. The median survival time of patients in group A and B was 7.3 months and 9.4 months, and in group C and D 4.0 months and 3.3 months. Identical growth patterns were found for marrow and blood cells in 21 of 27 patients studied and the number of clusters in blood and marrow showed a significant correlation (r = +0.96, P < 0.001). The mean 3H‐labelling index (LI) of myeloblasts determined in 32 patients was 14.8 ± 7.8% (SD). Patients with LI below 15 % tended to have a higher remission rate than patients with LI above 15 %. It is concluded that the in vitro growth pattern at diagnosis of bone marrow cells from patients with ANLL is of value in detecting patients with a poor response to current therapeutic protocols. Such information could possibly lead to alternative cytostatic regimes in these patients.
Chronic Idiopathic Thrombocytopenic Purpura (ITP): Site of Platelet Sequestration and Results of Splenectomy
Authors: Gugliotta Luigi , Isacchi Giancarlo , Guarini Anna , Ciccone Fabrizio , Motta Maria Rosa , Lattarini Cynthia , Bachetti Giuseppe , Mazzucconi Maria Gabriella , Baccarani Michele , Mandelli Franco , Tura Sante
Published: August 2010

51Cr‐platelet kinetics study was performed in 197 patients with chronic ITP after corticosteroid therapy had failed to induce a long lasting remission. The incidence of splenic, spleno‐hepatic, hepatic and diffuse platelet sequestration site was 58 %, 17 %, 6% and 19 %, respectively. Splenic and spleno‐hepatic sequestration sites were more frequent in patients less than 30 years old and in patients with a platelet count lower than 50 times 109/1. Ill patients were splenectomized shortly after the study. Normalization of the platelet count was obtained more frequently in patients with splenic and spleno‐hepatic sequestration than in the others. Labelled platelet sequestration site was the best predictor of the outcome of splenectomy. Platelet kinetics is a non‐invasive investigation that should be performed early after the diagnosis of chronic ITP in all patients eligible for splenectomy.
Chromosomal, Morphological and Clinical Correlations in Blastic Crisis of Chronic Myeloid Leukaemia A Study of 69 Cases
Authors: Alimena G. , Dallapiccola B. , Gastaldi R. , Mandelli F. , Brandt L. , Mitelman F. , Nilsson P. G.
Published: August 2010

The karyotypic pattern in 69 patients with Ph1‐positive chronic myeloid leukaemia (CML) was investigated during the blastic phase (BC) and correlated with survival and certain parameters of potential prognostic significance, including blast morphology, basophilia and thrombocytopenia.

There was no difference in median survival in BC between patients with and without aberrations in addition to the Ph1. Nor were there any differences in this respect among patients with the specific aberrations +Ph1, +8, iso(17q), or other abnormalities. There was no correlation between the incidence of thrombocytopenia and any particular karyotypic change. However, the incidence of basophilia was a characteristic feature for patients with an iso(17q).

The survival time in BC was considerably longer in patients with a lymphoid morphology of the blastic cells compared to the myeloid varieties, and within the myeloid varieties the survival in BC was longer in patients with granular differentiated blasts than in those with granular atypical blast cells.

No obvious correlation was apparent between blast morphology and karyotypic pattern. However, a pattern was discernible regarding survival and certain chromosomal changes within some morphologic groups: in patients with granular differentiated and lymphoid morphology, the median survival in BC was considerably longer when the bone marrow cells had a Ph1 as the sole abnormality compared to patients who had additional aberrations.