bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival following combination chemotherapy in advanced high grade non‐Hodgkin's lymphomas: Relation to proliferative activity of the lymphoma cells
Authors: Brandt Lars , Olsson Håkan
Published: July 2010

In 18 untreated adult patients (median age 62.5 yr) with advanced non‐Hodgkin's lymphoma of unfavourable histology, thymidine labelling indices (LIs) of the lymphoma cells were assessed. The patients were treated with combination chemotherapy and have been followed for 29–60 (median 52) months or until death. The survival curve had a steep fall during the first 2 yr. Between 2–5 yr after treatment there was a flattening of the curve and survival seemed to be similar to the survival expected for a Swedish population matched for age and sex. 11 patients died with 2 yr and 7 patients have survived for a longer period. Age, histopathologic classification and clinical stages were comparable in short‐term and long‐term survivors and treatment was not more aggressive for the long‐term survivors. The LIs were significantly higher (median 8.2) in short‐term survivors than in the long‐term survivors (median 1.4). Long‐term survival following combination chemotherapy of advanced NHL of unfavourable histology seems to be achieved mainly in patients with a low proliferative activity of the lymphoma cells. It is suggested that in NHL a high proliferative activity may facilitate the generation of new mutants and that some of these are spontaneously resistant to various chemotherapeutic drugs.
Nucleolus‐associated J chains in myeloma cells: Clinical significance
Authors: Kanoh Tadashi , Ohnaka Tadashi , Ohno Tatsuharu , Takamatsu Teruyuki , Yasuda Norimasa , Uchino Haruto , Niwa Yukie
Published: July 2010

Bone marrow aspirates from 20 patients with multiple myeloma (MM), 4 with smoldering multiple myeloma (S‐MM), 1 with idiopathic Bence Jones proteinuria (I‐BJP), and 6 with primary macroglobulinemia (PMG) were examined for nucleolus‐associated J chain. The incidence of nucleolar J chain‐positive (J +) cells among nucleolated cells producing M‐component was measured. This incidence (94.0–100%) in terminal MM was significantly higher than that (0–58.0%) in non‐terminal MM. Judging from a low incidence in the remission phase, chemotherapy might cause a selective elimination of less differentiated myeloma cells with J + nucleoli and might have some effect on J chain synthesis. The incidence of nucleolar J+ cells was very low in S‐MM. The IgM cells in PMG, where J chain is present in a disulfide‐linked form, had no or few J+ nucleoli. No correlation between the incidence of nucleolar J + cells among nucleolated plasma cells and the percentage of nucleolated cells or that of J + cells was found. Large J + nucleoli seemed to be another morphological feature indicating anaplastic myeloma cells. A high incidence of nucleolar J + cells may be one of the indicators for progressive disease.
Red cell membrane alteration involving protein 4.1 and protein 3 in a case of recessively inherited haemolytic anaemia
Authors: Morlé Laurette , Pothier Brigitte , Alloisio Nicole , Ducluzeau Marie‐Thérése , Marques Sandra , Olim Gabriel , e Silva João Martins , Féo Claude , Garbarz Michel , Chaveroche Isabelle , Boivin Pierre , Delaunay Jean
Published: July 2010

We present 2 siblings with a severe congenital haemolytic anaemia. Red cells displayed a variety of abnormal shapes, including leptocytes, schizocytes and elliptocytes. Repeatedly, skeletal protein 4.1 appeared reduced by 30%. The 4.1a/4.1b ratio was normal despite the haemolytic state. No change could be detected in spectrin, nor in sialoglycoproteins. Band 3 was denser, narrower and displaced downward. The parents, who are consanguineous, were devoid of any obvious biochemical abnormality; however, their red cells were not normal. These 2 cases with reduced protein 4.1 clearly depart from 4.1 (‐) hereditary elliptocytosis. The possibility of an altered binding of protein 4.1 to some other membrane component is discussed.
Monoclonal IgM with lupus anticoagulant activity in a case of Waldenström's macroglobulinaemia
Authors: Wisløff F. , Michaelsen T. E. , Godal H. C.
Published: July 2010

Strong lupus anticoagulant activity was detected in the plasma of a 73‐yr‐old woman with Waldenström's macroglobulinaemia. Purified patient IgM caused significant prolongation of the APTT in concentrations as low as 30 μg/ml, and its activity was inhibited by intact or (more effectively) by frozen‐thawed blood platelets. Employing varying concentrations of cephalin in the APTT assay, it was demonstrated that the macroglobulin had a direct cephalin‐neutralizing effect. When tested in an ELISA system using phospholipid‐coated microtiter wells, the IgM was shown to possess antibody activity against cephalin. With purified phospholipids as antigens, the protein was found to display antibody activity against phosphatidyl serine and phosphatidyl ethanolamine, which are main constituents of cephalin. These observations were confirmed in absorption experiments.
Inhibitory activity of a synthetic pentapeptide on leukaemic myelopoiesis both in vitro and in vivo in rats
Authors: Foa Paolo , Chillemi Francesco , Lombardi Luisa , Lonati Silvia , Maiolo Anna T. , Polli Elio E.
Published: July 2010

The synthetic pentapeptide pGlu‐Glu‐Asp‐Cys‐Lys has recently been proposed as the active component of a granulocyte‐derived inhibitor of normal haematopoiesis. We investigated its biological activity on leukaemic myelopoiesis both in vitro and in vivo in rats. Three different human permanent myeloid leukaemic cell lines (HL60, KG1, ML3) and a rat transplantable acute myeloid leukaemia (Shay leukaemia) were studied. Neither HL60 nor KG1 were sensitive to the peptide whereas a consistently reproducible inhibition of 3H‐TdR uptake was observed in ML3 cells. This effect was not due to a unspecific toxic action on target cells and was spontaneously reversible. When injected i.p. twice daily at an appropriate concentration in rats bearing Shay leukaemia, the peptide caused a significant increase in survival. Our results therefore indicate that the synthetic pentapeptide studied inhibits not only normal but also leukaemic myelopoiesis.
Monosomy 7 predisposes to diabetes insipidus in leukaemia and myelodysplastic syndrome
Authors: de la Chapelle Albert , Lahtinen Reino
Published: July 2010

We studied the chromosomes in the bone marrow of 4 patients who had both diabetes insipidus (DI) and acute non‐lymphocytic leukaemia. Clinical findings suggested that, in each case, myelodysplastic syndrome had preceded the onset of acute leukaemia. Two other such patients described in the literature had had a banded karyotype study of bone marrow cells. All 6 patients had deletions of chromosome 7. 3 had monosomy 7 as the sole cytogenetic abnormality, 2 had monosomy 7 associated with other clonal abnormalities and 1 had del(7)(q22) in association with other abnormalities. These data suggest that monosomy 7 or perhaps monosomy for 7q22‐qter predisposes to DI. The mechanism by which the proposed predisposition is produced remains to be clarified.
Germ‐line configuration of the T‐cell receptor beta‐chain gene in B‐cell chronic lymphoproliferative disorders which co‐express T‐cell antigens
Authors: Morabito Fortunato , Tassinari Angela , Callea Vincenzo , Brugiatelli Maura , Fierro Maria Teresa , Saglio Giuseppe , Neri Alberto , Foà Robert
Published: July 2010

In 7 cases of chronic B‐cell lymphoproliferative disorders – 6 chronic lymphocytic leukaemias and 1 non‐Hodgkin lymphoma in leukaemic phase – which co‐expressed T‐cell markers (CD3, CD2) the clonal origin was investigated at the DNA level. In accordance with the diagnosis, all cases showed a monoclonally rearranged configuration of the immunoglobulin genes. On the contrary, the T‐cell receptor beta chain gene always retained a germ‐line organization. These findings demonstrate that B‐cell chronic lymphoproliferative disorders which co‐express T‐cell‐related markers are truly composed of monoclonal B‐cell elements.
Interferon alpha‐2 for hairy cell leukemia: Evidence for induction of RNA synthesis in hairy cells and failure to correlate enhancement of natural killer cells with elimination of hairy cells
Authors: Schwarzmeier Josef D. , Schwabe Michael , Prischl Friedrich , Wagner Ludwig , Lion Thomas , Micksche Michael , Köller Ursula
Published: July 2010

The effect of human recombinant interferon α2 (IFNα2) on hairy cells obtained from 16 patients was evaluated. All patients promptly responded to induction of remission with 2 times 106 U/m2 interferon α2b, three times a week, sc. In order to achieve a more detailed insight into the mode of action of interferon in this disease, we determined the influence of IFNα2 on the incorporation of radiolabeled thymidine and uridine into hairy cells. While both 3H‐thymidine and 3H‐uridine incorporation were unaffected by IFNα2 in a 3‐hour incubation period, a significant increase in uridine incorporation into hairy cells, but not CLL cells, was observed after 24 h. Cell surface marker analysis performed with monoclonal antibodies did not reveal a quantitative alteration of the immunophenotype of hairy cells in vitro. In addition, natural killer cells, assessed by monoclonal antibodies and a cytotoxicity assay against K 562 cells, were found to be decreased in 9 out of 10 patients prior to therapy. Although IFNα2 could stimulate natural killer cells in vivo, we did not find a consistent correlation between the activation of these cells and the response to therapy. We conclude, therefore, that NK cells play no major role in the regression of hairy cells. Furthermore, IFNα2 does not alter antigenic determinants in vitro, but leads to an enhanced incorporation of 3H‐uridine into hairy cells in vitro, thus indicating a possible role for the induction of RNA synthesis in vivo.
Single‐dose pharmacokinetics of Factor IX evaluated by model‐independent methods
Authors: Longo G. , Cinotti S. , Filimberti E. , Giustarini G. , Messori A. , Morfini M. , Ferrini P. Rossi
Published: July 2010

We studied the pharmacokinetic data of 13 subjects with hemophilia B treated with a single‐dose of a Factor IX concentrate (Bebulin TIM2, N = 9; Preconativ, N = 4). The decay curves of Factor IX were evaluated by model‐independent methods and the following pharmacokinetic parameters (mean ± SD) were estimated: clearance (ml/h/kg) = 4.99 ± 2.01; mean residence time (h) = 22.9 ± 10.6; volume of distribution (ml/kg) = 99.9 ± 35.5. The in vivo recovery (59.8% ± 16.9%) was found to be inversely correlated with the volume of distribution. No significant difference in the pharmacokinetic parameters was found between patients treated with Preconativ and those treated with Bebulin. A model‐dependent compartmental evaluation of the 13 decay curves showed that the two‐compartment model was better than the one‐compartment model in 7 cases (53.8%), but the improvement of fit resulting from the two‐compartment model was statistically significant in only 2 cases (15.4%).
Splenic function in chronic myelogenous leukemia
Authors: Covas D. T. , Zago M. A.
Published: July 2010

Spleen function was evaluated by measurement of the clearance of autologous heat‐damaged 99mTc‐labelled erythrocytes from the circulation and into the spleen and the enumeration of pitted erythrocytes by interference contrast microscopy, and the spleen area was determined by scintillation scanning. All measurements were performed on 12 patients with chronic myelogenous leukemia and compared with 10 controls with apparently normal spleens, 6 splenectomized subjects and 9 patients with a reactive splenomegaly. Patients with CML had spleen function test results similar to normal controls in spite of having enlarged spleens whose projection area did not differ from that of the patients with reactive splenomegaly. Thus, patients with CML have a decreased spleen function per unit volume and signs of splenic hypofunction in the peripheral blood. The reduction of spleen function per unit volume in CML is the result of a severe decrease of the splenic blood perfusion which could result from the combined effects of the myeloid metaplasia and the increased whole‐blood viscosity due to high white‐cell counts.
FcR‐mediated clearance in thrombopenic and non‐thrombopenic patients with hemophilia A and possible relation of thrombopenia to HIV seropositivity
Authors: Auch D. , Budde U. , Hammerstein U. , Niese D. , Schmidt R. E. , Brackmann H. H. , Dengler H. J.
Published: July 2010

As morbidity of thrombopenia in hemophilia A patients is increasing, the pathogenetic influence of the reticuloendothelial system (RES) was measured using autologous anti‐Rh0(D)‐coated erythrocytes (EA) in 17 patients with or without thrombopenia. Mean survival of EA in patients was reduced to 53% of healthy controls (53.2 ± 46.1 min vs 100.5 ± 12.2 min; patients vs controls, mean ± S.D.). Survival of EA was not significantly different either in thrombopenic vs non‐thrombopenic nor anti‐HIV (human immunodeficiency virus) positive vs negative patients. Thrombopenia, elevated serum IgG and circulating immune complexes were related to the presence of anti‐HIV antibodies. EA survival was also decreased in the absence of anti‐HIV antibodies. This indicates activation of RES by a mechanism different from retroviral infection by HIV (1).
Urinary hydroxyproline excretion in the myelofibrosis‐osteomyelosclerosis syndrome and related diseases
Authors: Hasselbalch Hans
Published: July 2010

The total urinary hydroxyproline excretion was assessed in 47 patients with chronic myeloproliferative disorders. Urinary hydroxyproline excretion was normal in 16 patients with idiopathic myelofibrosis and in 5 out of 6 patients with acute myelofibrosis. In patients with osteomyelosclerosis (n = 8) values for urinary hydroxyproline excretion were higher (median 202, range 54–652) than those in idopathic myelofibrosis (median 139, range 84–216). This difference was not significant (p > 0.1). Elevated values for urinary hydroxyproline excretion were found in 10 patients (1 AMF patient, 3 OMS patients and 6 patients with CML in the accelerated phase of the disease). All but 1 of these patients had been treated, or were being treated, with cytotoxic agents at the time of investigation. These findings are compatible with impaired degradation of bone marrow collagen which, together with enhanced collagen synthesis from bone marrow fibroblasts, accounts for progressive accumulation of connective tissue in the bone marrow. This process appears to be influenced by cytotoxic treatment as reflected in increased urinary hydroxyproline excretion in those patients receiving cytotoxic agents.
Hb Linköping (β 36 Pro → Thr): A new high oxygen affinity hemoglobin variant found in two families of Finnish origin
Authors: Berlin Gösta , Wranne Bengt , Jeppsson Jan‐Olof
Published: July 2010

Several members representing three generations of two families with erythrocytosis due to a newly described hemoglobinopathy (Hb Linköping, β 36 Pro → Thr) were studied. All affected family members had a pronounced left‐shift of the oxygen dissociation curve, indicating an increased oxygen affinity leading to compensatory erythrocytosis. The proband of each family was found by a simple method determining the oxygen pressure at half hemoglobin saturation (P50), which was used as a screening test evaluating patients with polycythemia. In both cases the hemoglobinopathy was missed by routine hemoglobin electrophoresis. The abnormal hemoglobin was confirmed by isoelectric focusing and the altered amino acid sequence was identified by reversed‐phase high‐performance liquid chromatography (HPLC). The importance of a correct diagnosis in patients with erythrocytosis due to high‐affinity hemoglobin variants is discussed.
An increase in basophils in a case of acute myelomonocytic leukaemia associated with marrow eosinophilia and inversion of chromosome 16
Authors: Matsuura Yoshifusa , Sato Noriharu , Kimura Fumihiko , Shimomura Satoshi , Yamamoto Koichiro , Enomoto Yasuhiro , Takatani Osamu
Published: July 2010

A patient with acute myelomonocytic leukaemia (M4 subtype) with pericentric inversion of chromosome 16, inv(16)(p13q22), and a marked basophilia is described. Results from transmission electron microscopy suggested that the basophils were immature. Clinically, although leukaemic cells had a tendency to infiltrate a number of tissues and organs, such as skin, gingiva, liver and lung, the patient was successfully treated with chemotherapy. The increase in basophils accompanied by marrow eosinophilia may be the result of abnormal differentiation of leukaemic cells that have the capacity to differentiate into both the eosinophilic and basophilic pathways.
Pancreatic carcinoma associated with marked eosinophilia: A case report
Authors: Hirata Jouji , Koga Teruhito , Nishimura Junji , Ibayashi Hiroshi
Published: July 2010

A case of pancreatic carcinoma associated with marked eosinophilia is reported. A 71‐yr‐old man was admitted to hospital because of melena and abdominal pain. The systematic examinations revealed pancreatic adenocarcinoma with multiple metastases (rectum, lung and brain). The leukocyte count was gradually increased and reached up to 81.7 times 109/1, of which 54% consisted of eosinophils. Colony‐stimulating factor (CSF) was detected both in the patient's serum and in the tumor extracts by a normal human bone marrow culture system. The colonies which were stimulated with patient's serum largely consisted of granulocyte, granulocyte/macrophage and eosinophil types. These results suggest that blood leukocytosis and eosinophilia were due to a high concentration of plasma CSF, which was probably produced by the tumor cells.
Life‐threatening reaction to factor VIII concentrate in a patient with severe von Willebrand disease and alloantibodies to von Willebrand factor
Authors: Mannucci P. M. , Tamaro G. , Narchi G. , Candotti G. , Federici A. , Altieri D. , Tedesco F.
Published: July 2010

A 16‐yr‐old girl with severe von Willebrand disease complicated by the development of precipitating alloantibodies to von Willebrand factor (anti‐VWF) had a life‐threatening anaphylactoid reaction immediately after the infusion of a commercial plasma concentrate of factor VIII/von Willebrand factor. An early post‐infusion activation of the complement system was demonstrated by the appearance of C3 split products and by the drop of serum CH50 activity, occurring in parallel with a post‐infusion drop in the anti‐VWF antibody levels. Immune complexes remained unchanged in the early post‐infusion period and rose to a moderate extent only after 24 h. We conclude that biologically active products of the complement system contributed to the onset of this life‐threatening reaction which occurred after concentrate infusion.
Prognostic relevance of serum‐markers in relation to histopathology, stage and initial symptoms in advanced low‐grade non‐Hodgkin lymphomas
Authors: Martinsson Ulla , Glimelius Bengt , Hagberg Hans , Sundström Christer
Published: July 2010

The prognostic relevance of 4 different serum markers (deoxythymidine kinase = S‐TK, lactic dehydrogenase = S‐LDH, S‐Haptoglobin and S‐Orosomucoid) in relation to histopathology according to the Kiel classification, stage and presence or absence of initial symptoms were investigated in 168 consecutive cases of low‐grade non‐Hodgkin lymphomas (NHL). All serum markers, as well as the other three parameters, gave prognostic information. Univariate analysis yielded a high predictive value (p<0.0002) for both S‐TK and S‐LDH. The best information regarding the probability of survival was, however, obtained from the presence or absence of symptoms from lymphoma manifestations other than those caused by a strictly local tumor mass. Since S‐TK and S‐LDH correlated well with each other, only the better of them, S‐TK, gave information additional to initial symptoms in a multivariate test.
Human myeloma: Several subsets of circulating lymphocytes express plasma cell‐associated antigens
Authors: Boccadoro M. , Omedé P. , Massaia M. , Dianzani U. , Pioppo P. , Battaglio S. , Meregalli M. , Pileri A.
Published: July 2010

Peripheral blood lymphocytes from 9 monoclonal gammopathies of undetermined significance (MGUS) and 27 multiple myelomas (MM) were studied with a panel of monoclonal antibodies (MoAb) that recognize B and T lymphocytes and plasma cells. No difference in the percentage of B lymphocytes, identified by B1 and B4 MoAb, was observed in MGUS and MM patients versus normal controls. However, high percentages of circulating lymphocytes expressing plasma cell‐associated antigens were detected in MM (HAN‐PC1 + = 29.4 ± 20.4%; TEC‐T10+ = 27.8 ± 19.2%) whereas they were in the normal range in MGUS (HAN‐PC1 + = 8.8 ± 5.8% p = 0.006; TEC‐T10+ = 5.7 ± 4.7% p<0.001). Almost identical results were obtained using PCA‐1 MoAb in 17 of these patients. TEC‐T10+ and PCA‐1 + lymphocytes were sorted and re‐analyzed with phycoerythrin conjugated MoAb in 3 healthy subjects, 2 MGUS, and 4 MM patients. In normal subjects and in MGUS the majority of PCA‐1 + cells belonged to the B lineage (Leu 2‐, Leu3‐, Leu 15‐, HLA‐Dr +), whereas the majority of TEC‐T10+ cells are represented by activated T cells and NK cells (Leu 15 +). In MM an abnormal expansion of T lymphocytes was chiefly responsible for the high values of lymphocytes expressing plasma cell‐associated antigens. Moreover, in MM a clinical evaluation showed a correlation between the presence of these lymphocytes and an aggressive disease. Indeed, they can be considered a useful prognostic marker.
Refractoriness to α‐interferon (Intron A) in previously chemotherapy‐treated patients with chronic myelocytic leukaemia
Authors: Friche E. , Hansen M. M. , Wieslander S.
Published: July 2010

8 patients with chronic myeloid leukaemia in the chronic phase who had previously received chemotherapy were given α‐interferon (Intron A). The Intron A was administered subcutaneously at a dose of 2 × 106 I.U./m2 three times a week and this was increased to 4–5 million I.U./m2 daily if no response was obtained after 6–8 months. 1 patient was Philadelphia chromosome‐negative and was the only one who showed a major response to treatment. The other 7 patients never achieved haematologic remissions, or even a significant reduction in the immature blood leucocyte count or spleen size.
Possible mechanism of ineffective erythropoiesis by an altered transferrin receptor cycle in erythroleukemia
Authors: Muta K. , Nishimura J. , Yamamoto M. , Ideguchi H. , Katsuno M. , Ibayashi H.
Published: July 2010

Involvement of the transferrin receptor cycle was noted in erythroblasts from a patient with erythroleukemia (FAB classification M6). The kinetics of transferrin receptor cycle in bone marrow erythroblasts was obtained by pulse‐chase experiments before the initiation of therapy. Internalization of transferrin was impaired and resulted in a delayed peak of internalized transferrin, as compared with the kinetics pattern seen in healthy subjects. The subsequent exocytosis of the internalized ligand was also delayed. Thus, transferrin receptor cycle seems to be influenced all along the transferrin pathway, hence transferrin travels more slowly in erythroblasts in erythroleukemia. The altered transferrin receptor cycle led to a diminished iron uptake per surface transferrin receptor (approximately 30% of that in healthy subjects), and the incorporation of iron into heme was greatly reduced. Our observations suggest a possible role for the altered transferrin receptor cycle in the pathogenesis of defective heme synthesis and ineffective erythropoiesis in erythroleukemia.
Zygomycosis in aplastic anaemia: Response to a combined regimen of amphotericin B and antilymphocyte globulin
Authors: Rahemtulla A. , Durrant S. T. S. , Coonar H. S. , Lee K. W. , Gordon‐Smith E. C.
Published: July 2010

A 22‐yr‐old man with aplastic anaemia was treated with high dose methylprednisolone. A month later he developed severe epistaxis which was not controlled by regular platelet transfusions. A balloon catheter inserted into the left nostril caused necrosis of the left ala nasi accompanied by gross facial oedema. He received treatment with horse ALG for aplastic anaemia but developed gross facial oedema and anaesthesia of incisor and canine teeth on the right side. Radiographs initially showed thickening of the maxillary antral mucosa and later erosion of the maxilla over the anaesthetic region. A biopsy specimen of this region contained hyphae of zygomycetes. He was treated with amphotericin B and a second course of antilymphocyte globulin followed by oxymetholone. He has made a satisfactory clinical and haematological recovery.
Refractory anaemia according to the FAB classification: A report on 69 cases
Authors: Fenaux P. , Estienne M. H. , Lepelley P. , Zandecki M. , Lai J. L. , Beuscart R. , Jouet J. P. , Cosson A. , Bauters F.
Published: July 2010

Between 1980 and 1986, we diagnosed refractory anaemia (RA), according to the FAB classification, in 69 patients, who constituted 22% of the 312 cases of myelodysplastic syndromes (MDS) seen over that period. The haematological features were variable, with pancytopenia in 14 cases (20%), bicytopenia in 24 (36%) and mono‐cytopenia in the remaining patients, including 21 (30%) cases of anaemia alone, 8 (12%) cases of refractory neutropenia and 2 (3%) cases of refractory thrombocytopenia. Myelodysplastic features were also quite variable, involving one, two or all three lineages. In patients with a single cytopenia or only one dysplastic lineage, FAB criteria appeared insufficient for adequate inclusion among RA and we suggest more precise diagnostic criteria, resulting from the utilization of cytogenetics, ferrokinetics, progenitor cultures and perhaps molecular biology, in such cases. Median survival was 42 months. 12 patients (17%) progressed to RAEB (of whom 7 finally developed ANLL) and 4 patients (6%) to CMML. In spite of the heterogeneity of haematological features, only two factors were associated with poor prognosis, namely age > 70 yr at diagnosis and haemoglobin<10 g/dl, whereas, to a lesser extent, neutropenia was associated with progression to RAEB.
Platelet associated IgG, platelet mean life span and treatment with intravenous immunoglobulin in idiopathic thrombocytopenic purpura
Authors: Nieminen U. , Syrjälä M. , Ikkala E. , Myllylä G.
Published: July 2010

The clinical significance of platelet associated IgG in ITP detected by direct platelet suspension immunofluorescence test (PSIFT) was studied. The platelet mean life span (MLS) was measured with 111In‐labelled platelets in 17 adult patients. All the patients had shortened platelet MLS. The direct PSIFT was positive in 14 patients. Patients were initially treated with prednisone; 12 patients with poor response to the drug were splenectomised. 8 of these 12 patients were treated with intravenous immunoglobulin (IvIg) before splenectomy. The response to IvIg was as good or better in the 3 patients with negative PSIFT, than in the 5 patients with positive PSIFT.
A method combining morphological, immunocytochemical and chromosomal examinations of the same cell in the study of lymphoproliferative diseases
Authors: Franssila K. O. , Lindholm C. , Teerenhovi L. , Knuutila S.
Published: July 2010

6 cases of different lymphoproliferative diseases were studied with the new MAC (Morphology‐Antibody‐Chromosome) method in order to find out 1) if the abnormal karyotype is confined to the monoclonal cell population, 2) if there are, within this clone, also cells with a normal karyotype, and 3) if the method can help the pathologist to diagnose malignant lymphoproliferative diseases. The MAC method allows a simultaneous study in the same metaphase cell of the karyotype, surface markers, and some morphological features. In all cases in which a monoclonal cell proliferation was detected immunohistologically, the MAC examination showed a chromosomal abnormality for the same light chain as was detected in immunohistology, but not in other cells. In all but a single case, all mitotic cells belonging to the clonal cell proliferation had an abnormal karyotype. In this case with lambda clonality, 2/8 lambda‐positive mitoses had a normal karyotype. However, all the normal mitoses occurred in small lymphocytes whereas the abnormal mitoses were seen in large blastic cells. In 1 case, the MAC method helped in confirming the diagnosis of malignant lymphoma (nodular small cleaved cell type). Especially in lymphomas composed of a mixed cell population, the MAC method makes it possible to find out which cell types have an abnormal karyotype and which have a normal karyotype.
Use of splenic volume estimation to distinguish primary thrombocythaemia from reactive thrombocytosis
Authors: Messinezy M. , Chapman R. , Dudley J. M. , Nunan T. O. , Pearson T. C.
Published: July 2010

Splenic volume was measured by visual assessment of planar images of the spleen, and also by single photon emission computerised tomography (SPECT) using 99mtechnetium tin colloid, in a group of 33 patients with primary thrombocythaemia (PT) or reactive thrombocytosis. Volumes greater than 337 cm3 correlated strongly though not absolutely with PT, all patients with volumes greater than this figure being in the PT group. Simple visual assessment of planar images by an experienced observer matched measured splenic volumes very closely.
Methylprednisolone therapy in aplastic anaemia: Correlation of in vitro tests and lymphocyte subsets with clinical response
Authors: Issaragrisil S. , Tangnai‐Trisorana Y. , Siriseriwan T. , Chinprasertsuk S. , Piankijagum A. , Sarasombath S.
Published: July 2010

20 patients with aplastic anaemia were treated with methylprednisolone 1 g/d for 3 d followed by prednisolone 60 mg on alternate days. At 3 months after therapy, 7 of 20 patients (35%) showed recovery, 2 had died and 11 were non‐responders. Only newly diagnosed patients were responders. Results of in vitro tests were correlated with clinical response. The first test was designed to determine whether removing various subpopulation of cells would increase the numbers of progenitor cells. In the second test blood cells were collected at 1 month after starting treatment and assayed for progenitor cells. Data from both tests did not correlate with the response to therapy. Lymphocyte subsets were measured in the blood before and at 1 month after treatment. The absolute numbers of OKT3 +, OKT4 + and OKT8 + cells were significantly decreased compared to the normal population. The number of HNK1 + cells was also decreased but no significant difference was observed. Responders had a higher number of HNK1 + cells compared to non‐responders. No significant differences of OKT3 +, OKT4+ and OKT8+ cells among responders and non‐responders were observed. Therefore a high number of HNK1 + cells prior to therapy may identify patients responding to the treatment.
Genetic factors involved in human Gγ and Aγ globin gene expression
Authors: Bouhass R. , Taleb‐Bendiab R. , Starck J. , Morle F. , Aguercif M. , Godet J.
Published: July 2010

Gγ to Aγ globin ratios, haplotypes at the β globin gene cluster and the C →T substitution at ‐158 5′ to the Gγ globin gene were studied in three Algerian families that include SS or S‐β°thal patients. Gγ to Aγ ratios were found similar, within a family, in subjects displaying the same combination of chromosomes 11, the ratio observed for a given combination depending on the chromosome haplotypes. Our data can be explained by the existence of several alleles of a genetic factor closely linked to the β globin gene cluster and involved in the determination of Gγ to Aγ globin ratio.
Liver involvement at diagnosis of primary myelofibrosis: A clinicopathological study of twenty‐two cases
Authors: Pereira A. , Bruguera M. , Cervantes F. , Rozman C.
Published: July 2010

Liver biopsies were carried out at diagnosis in 22 patients with primary myelofibrosis. Pathological changes were semiquantitatively evaluated and correlated with either liver function tests, peripheral blood features, bone marrow biopsy changes or patient survival. Hepatic myeloid metaplasia (HMM), primarily consisting of the presence of morphologically abnormal megakaryocytes, was found in all cases. Other remarkable pathological changes included increased reticulin network, sinusoidal widening not related to the intensity of HMM, and iron overload in the absence of previous blood transfusions. High serum alkaline phosphatase was the most frequent biochemical abnormality, and reflected rather the presence of sinusoidal widening than the degree of HMM. The number of immature myeloid cells was the only peripheral blood parameter positively correlated with the degree of HMM. No relationship could be established between bone marrow changes and the degree of HMM. Finally, patients with mild HMM survived longer than those showing marked HMM.
Resistance of some leukemic blasts to lysis by lymphokine activated killer (LAK) cells
Authors: Panayotides P. , Porwit A. , Sjögren A‐M , Wasserman J. , Reizenstein P.
Published: July 2010

Peripheral blood mononuclear cells (PBMC) from healthy donors and AML patients in remission were stimulated with phytohemagglutinin (PHA) and recombinant inter‐leukin‐2 (IL‐2). These stimulated cells (lymphokine activated killer (LAK) cells) showed increased DNA synthesis as measured by 3H‐Thymidine uptake. A synergistic effect of PHA and IL‐2 was found. LAK cells' ability to kill acute myeloid leukemia (AML) blasts was investigated by the 51Cr release assay. LAK cells showed a cytotoxicity (over 10% specific 51Cr release) against 9/12 leukemic blasts, even at effector/target (E/T) ratios as low as 5:1. However, on average only 22.2% (SD 11.8) and 36.5% (SD 12.5) 51Cr release were obtained in 4‐ and 18‐hour cytotoxicity assays, respectively, at an E/T ratio of 20:1. Leukemic blasts in 3/12 AML cases and normal PBMC were entirely resistant to lysis, even at an E/T ratio of 80:1. Susceptibility to lysis was not correlated to peanut‐agglutinin receptor expression. LAK cells were more cytotoxic towards the K‐562 cell line (natural killer activity) than unstimulated PBMC.
Total absence of eosinophils in a patient with chronic urticaria and vitiligo
Authors: Juhlin L. , Venge P.
Published: July 2010

A 71‐year‐old woman with chronic urticaria and vitiligo is reported who lacked eosinophil and basophil leukocytes in her blood, bone‐marrow and skin. No IgE was detectable in serum. She had a low level of serum eosinophil cationic protein (ECP) which could indicate that some eosinophils had been formed but rapidly destroyed. There was, however, no ECP release when the patient's serum was mixed with heterologous eosinophils. Staining for eosinophilic proteins in white blood cells by monoclonal antibodies revealed no storage or secreted forms of ECP. The source of ECP in our patient therefore remains unknown.
Pure red cell aplasia: Stable complete remission following antilymphocyte globulin administration
Authors: Jacobs P. , Wood L.
Published: July 2010

A 25‐yr‐old woman with idiopathic pure red cell aplasia achieved complete remission following a single 5‐day course of antilymphocyte globulin at a dose of 50 mg/kg daily by intravenous injection as initial and sole therapy. Apart from transient arthralgia and asymptomatic thrombocytopenia there were no side effects. At 2 yr, the patient has normal peripheral blood, bone marrow and in vitro culture studies. This approach offers an alternative to conventional immunosuppressive therapy where there is evidence of an underlying immune disorder.
Hypocholesterolemia in acute myelogenous leukemia
Authors: Reverter J. C. , Sierra J. , Marti‐Tutusaus J. M. , Montserrat E. , Grañena A. , Rozman C.
Published: July 2010

Plasma‐cholesterol concentrations were determined in 85 acute myelogenous leukemia patients. Measurements were repeated in 28 cases during remission. Mean plasmacholesterol concentration (± SD) at diagnosis was 3.95 mmol/l (± 1.29). 47 patients (55.3%) had hypocholesterolemia (< 3.87 mmoi/l). Among the main clinical, hematologic and biochemical parameters, only high leukocyte counts were correlated with hypocholesterolemia. As far the FAB subtypes are concerned, the lowest cholesterol levels were observed in leukemias with monocytic component. However, although the same FAB subtypes showed significantly higher leucocytes counts than the other subtypes, both parameters were independently related to low cholesterol levels. Remission was associated with a significant increase in cholesterol levels in those patients with low cholesterol concentrations or high leukocyte counts at diagnosis. These results support the idea that initial hypocholesterolemia in acute myelogenous leukemia is related to the tumoral mass present at diagnosis.
Effect of chronic ethanol administration on iron metabolism in the rat
Authors: Sánchez J. , Casas M. , Rama R.
Published: July 2010

This study shows that the ingestion of ethanol provokes alterations in iron metabolism which may lead to iron overload. Impaired release of reticuloendothelial iron was shown by a decrease of the maximum red blood cell utilization when radioactive iron was supplied as colloidal iron. An impairment in the erythropoietic activity of ethanol‐treated animals was also observed, as can be seen from the reduced plasma iron turnover and red blood cell utilization within 24 h of iron administration. A rise in marrow transit time was also observed. In ethanol‐treated rats there was an increase in the amount of iron retained both in the liver and the spleen. This was observed in both sexes and also in the offspring from ethanol‐treated mothers.
Pseudo grey platelet syndrome — Grey platelets due to degranulation in blood collected into EDTA
Authors: Cockbill S. R. , Burmester H. B. C. , Heptinstall S.
Published: July 2010

We have studied a woman with a history of mild bruising and bleeding, with a normal platelet count and normal clotting factors, who had platelets that appeared grey when stained and viewed under the microscope. Unlike the grey platelet syndrome, the abnormality was only evident when blood had been collected into EDTA and not when citrate or heparin was used as anticoagulant. This ‘pseudo grey platelet syndrome’ was associated with platelet dense body and alpha granule secretion with no aggregation and occurred on removal of extracellular Ca2+. We discovered that a plasma factor was responsible which could be an immunoglobulin but which is clearly different from the EDTA‐sensitive antibodies which cause platelet aggregation and agglutination. We were not able to demonstrate a relationship between the mild bleeding tendency and the in vitro abnormality.
Biochemical and immunologic abnormalities in peripheral blood T lymphocytes of patients with hemophilia A
Authors: Dianzani Umberto , Pileri Alessandro , Bianchi Alberto , Camponi Alessandro , Tamponi Giacomo , Massaia Massimo
Published: July 2010

Subset distribution, ecto‐5′nucleotidase (5′NT) activity, and the generation of allospecific cytotoxic T lymphocytes (CTL) were investigated in peripheral blood T lymphocytes from 39 hemophilia A patients divided into three groups: group A and group B (HIV‐patients with CD4:CD8 ratio < 1 and > 1 respectively), and group C (HIV+ patients). 5′NT activity was significantly decreased compared with healthy controls in groups B and C. In group B, this deficiency was attributable to expansion of CD8+ CD11+ suppressor cells. In group C, activated (HLA‐DR +) CD8+ cells were also present and contributed to 5′NT deficiency. The suppressor cell expansion seemed to be mainly related to AHF infusions, whereas HLA‐DR expression was related to HIV infection. CD11+ and HLA‐DR + cells were also expanded in the CD4+ subpopulation of all three groups, whereas CD4+ CD28+ lymphocytes were significantly decreased in group C only. Lastly, alloreactive cytotoxicity was decreased in group B and was normal in groups A and C.
Bone marrow karyotype and prognosis in primary myelodysplastic syndromes
Authors: Billström Rolf , Thiede Torben , Hansen Sören , Heim Sverre , Kristoffersson Ulf , Mandahl Nils , Mitelman Felix
Published: July 2010

Bone marrow karyotype, survival time, and the rate of progression to leukaemia were studied in 111 unselected patients with primary myelodysplastic syndromes. The 49 patients (44%) with clonal chromosome aberrations had survival time (median 29 months) similar to that found in the 62 patients with normal bone marrow karyotype (24 months, p > 0.10). The presence of multiple (> 2) abnormalities (17 patients) was strongly associated with poor prognosis, with a median survival of only 7 months (p < 0.001). Prognostic information could be attributed to 2 specific abnormalities, del(5q) and ‐7: Presence of del(5q) as the sole anomaly was associated with long survival (36+ months), whereas monosomy 7 was a bad prognostic sign (6 months). The risk for leukaemia development correlated neither with the number of chromosome abnormalities nor with any particular anomaly. Our findings demonstrate the prognostic importance of quantifying the complexity of bone marrow chromosome changes. They also emphasize that different specific abnormalities convey widely different prognostic information in primary myelodysplastic syndromes.
Eosinophilic spleen colonies are produced in rat‐marrow‐transplanted but not in murine‐marrow‐transplanted mice
Authors: Szabó László G. , Kelemen Endre
Published: July 2010

Differential counts of about 5000 splenic clusters and colonies developing in whole‐body‐irradiated mice and rats were made, using semi‐serial histological sections prepared 9 to 12 d after transplantation with bone marrow haemopoietic cells. The investigated mouse and rat spleens were from syngeneically, allogeneically, or xenogeneically transplanted recipients. Splenic eosinophil clusters were always found when rat eosinophil‐producing progenitors were present in the inoculum, whereas murine inocula failed to produce splenic eosinophilic clusters even in the syngeneic mouse. The limiting factor in the production of splenic eosinophilic clusters was the appropriate donor progenitor/committed stem cell itself. Changes in the percentages of eosinophil clusters with the number of injected cells and with increased doses of irradiation, as well as formation of rat eosinophil colonies in mice, as against mainly clusters in rats, themselves show that regulatory mechanisms of the recipients also play a role. These regulatory mechanisms cannot be attributed to the splenic microenvironment.
Factors influencing release of granulocyte‐macrophage colony‐stimulating activity from human mononuclear phagocytes*
Authors: Fibbe W. E. , Kluck Petra M. C. , Duinkerken Nelleke , Voogt Paul J. , Willemze Roel , Falkenburg J. H. Frederik
Published: July 2010

Mononuclear phagocytes play an important role in the regulation of hematopoiesis, not only by producing regulatory monokines such as prostaglandins, tumor necrosis factor and interleukin‐1 (IL‐1), but also by the production of colony‐stimulating activity (CSA). Previously, we have demonstrated that granulocyte‐macrophage CSA (GM‐CSA) production by mononuclear phagocytes can be induced by IL‐1. In the present study, the influence of culture conditions on the production of GM‐CSA was studied. It was found that both human sera and fetal bovine sera contain constituents — at present undefined — that induce GM‐CSA production. These factors are distinct from IL‐1 and lipopolysaccharide. In selected experiments, no GM‐CSA‐inducing effect of serum was found, suggesting that the effect may be donor‐related. GM‐CSA release in the presence of serum could be reduced by 40% after incubation of mononuclear phagocytes at low cell concentrations in methylcellulose, indicating that intimate cell‐cell contact is an additional factor that enhances GM‐CSA release.
Prognostic factors in Hodgkin's disease stage IV
Authors: Specht Lena , Nissen Nis I.
Published: July 2010

104 patients with previously untreated Hodgkin's disease stage IV were examined and treated at the Finsen Institute between 1969 and 1983. 99 patients were treated with combination chemotherapy (MOPP or equivalent regimens) with or without additional irradiation of some involved areas. Prognostic factors including age, sex, peripheral plus intrathoracic nodal tumour burden, intraabdominal nodal tumour burden, B‐symptoms, histologic subtype, number of involved nodal regions, mediastinal involvement, number of involved extranodal sites, type of extranodal involvement, ESR, and haematologic and other blood values, together with exploratory laparotomy and treatment were examined in multivariate analyses. With regard to disease‐free survival, the only factors of independent prognostic significance were sex and lymphocytopenia. With regard to overall survival the factors of independent significance were age, sex, bone marrow involvement, and an elevated serum creatinine. If only deaths of Hodgkin's disease were considered in overall survival, both lymphocytopenia and bone marrow involvement had independent prognostic significance. These two factors thus emerged as the most important prognostic factors in disseminated Hodgkin's disease, and both would appear to be related to the patient's total tumour burden.
Analysis of leucocyte differentiation antigens in blood and bone marrow in patients with refractory anaemia (RA) and RA with sideroblasts. Prognostic implications of sequential and follow‐up data
Authors: Kerndrup Gitte , Bendix‐Hansen Knud , Pedersen Bent , Ellegaard Jørgen , Hokland Peter
Published: July 2010

34 patients with primary myelodysplastic syndrome (MDS), initially diagnosed as subtypes refractory anaemia (RA) and RA with ringed sideroblasts (RA‐S), were followed to investigate the distribution of lymphoid and myeloid differentiation antigens in the blood and bone marrow in search of potential prognostic significance with regard to progression to RA with an excess of blasts (RAEB) or acute myeloid leukaemia, and for relations to clinical, morphological and cytogenetic findings. Patients who later progressed to RAEB had significantly decreased percentages of anti‐T8 positive T‐suppressor cells in the blood at diagnosis compared to those who did not (p = 0.05). Sequential analysis showed a decrease with time also in the percentages of anti‐T8‐positive cells (p = 0.05). In the bone marrow, progressing patients initially showed significantly increased percentages of anti‐My9‐positive immature myeloid cells (p < 0.001), and the percentages of anti‐My9‐positive cells in the bone marrow increased with time (p < 0.005). Analysis of the pooled data revealed a statistically significant relation between increasing percentages of anti‐My9‐positive cells and the frequencies of clonally abnormal (p < 0.001) and abnormal (p = 0.004) metaphases.
Management of polycythaemia vera, essential thrombocythaemia and myelofibrosis with hydroxyurea*
Authors: Löfvenberg Eva , Wahlin Anders
Published: July 2010

A total of 59 symptomatic patients with myeloproliferative disorders (polycythaemia vera 24 pats., essential thrombocythaemia 25 pats., myelofibrosis 10 pats.) and elevated platelet counts were studied during 1653 months of continuous treatment with hydroxyurea. Reduction of the platelet level to < 500 × 109/1 was achieved within 8 weeks in 86% of polycythaemia pats., 80% of thrombocythaemia pats., 60% of myelofibrosis pats. Control of disease‐related symptoms was achieved within 1 year in 78% of the patients. There was no instance of severe bone marrow toxicity. Side‐effects of hydroxyurea were modest. Survival was excellent, with 86% probability of survival after 5 yr of therapy. We consider hydroxyurea a first‐choice alternative in the treatment of patients with polycythaemia vera, essential thrombocythaemia and mylofibrosis with thrombocytosis.