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Biomedical subjects

B Varet

Publications and source records attributed to B Varet.

At least 19 recordsLinked to original sources

High-dose recombinant human erythropoietin administered intravenously for the treatment of anaemia in myelodysplastic syndromes.

As the importance of recombinant human erythropoietin (r-HuEPO) therapy has been clearly demonstrated in anaemic patients with chronic renal failure (CRF), we carried out an open, non-randomized, non-placebo-controlled trial of high-dose intravenous (i.v.) r-HuEPO (100,000 U twice weekly) therapy in 14 anaemic, transfusion-dependent patients. Clinical response was defined by a rise in haemoglobin concentration to 9-11 g/dl and/or a reduction in the transfusion requirement during the treatment period compared with the 12 weeks before treatment. Eight patients completed the 12-week treatment and 4 were still under treatment, 1 at 10 weeks, 2 at 8 weeks and 1 at 4 weeks. Only those patients completing treatment were included in the efficacy evaluation. After treatment there was no significant change in haemoglobin concentrations, reticulocyte counts, or transfusion requirements. However, the number of patients included is too low to allow any definitive conclusion to be made.

Adult

[Auto-immune hemolytic anemia associated with Kaposi's sarcoma. Report of a new case (author's transl)].

The association of Kaposi angiosarcomatosis and an auto-immune haemolytic anaemia is reported in a 69-year-old woman. The direct Coombs test was "igG complement" type positive. This is the 5th reported case and the 2nd in which haemolysis developed during an acute malignant exacerbation of the disease. The patient died less than 4 months following the diagnosis of Kaposi's sarcoma, after treatment with prednisone and chlorambucil. Lymphoid and immunological abnormalities are not rare during the course of Kaposi's sarcoma. The reasons are discussed briefly.

Aged

[In vitro study of erythroblast precursors in Vasquez disease (polycythemia vera). Arguments in favor of a double population of erythroblastic stem cells in the bone marrow].

In vitro studies using the plasma clot culture system have been performed in order to compare the red cell pregenitors able to rise to erythrocytic colonies in 7 days (CFUE) in the bone marrow of polycythemia vera (PV), secondary polycythemias and normal subjects. In PV but never in normal individuals or secondary polycythemias, the bone marrow cells producing erythroid colonies without addition of erythropoietin were found. The erythropoietin dode response curves in PV is biphasic with a plateau up to a concentration of erythropoietin of 0.02-0.05 i.U./ml followed by a near normal response to erythropoietin at higher doses. Thus our results demonstrate that two populations of erythroid stem cells coexist in PV, one being abnormally sensitive to (or independant of) erythropoietin, the other normally responding to erythropoietin. After remission induced by P32 treatment, the abnormal population can disappear but the prognostic significance of this disappearance is uncertain. On the whole these results are in agreement with those of others laboratories using the plasma clot culture system. The reasons of the disagreement with the data published using the methylcellulose technic of culture are discussed.

Animals

[Hemolytic anemia].

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Anemia, Hemolytic

[Demonstration of erythroblastic differentiation after 14 days in blood in vitro during Vaquez's disease without addition of erythropoietin].

Leucocytes of normal individuals and patients with polycythemia vera were isolated from the peripheral blood by Ficoll-Hipaque density gradient centrifugation and cultured in vitro suing the bovine plasma clot culture technique with a minor modification: the addition of fresh normal serum. After 14 days in the presence of sheep erythropoïetin (3U/ml) erythropoïetic bursts containing between 3 and 10 subcolonies were observed in normal and polycythemia vera cultures. Blood leucocytes of patients with polycythemia vera rise to these erythropoïetic bursts without addition of erythropoïetin to the culture. This behavior was never observed in the blood of normal individuals. These results indicate that in polycythemia vera commited erythroïd stem cells of high proliferative capacity closely resembling the murine erythroïd burst forming unit have an abnormal sensitivity to erythropoïetin as well as the immediate precursors of the proerythroblasts. The culture of these cells from the peripheral blood offers some practical advantages.

Cell Differentiation

[In vitro study of erythroid precursors in Vaquez' disease (polycythemia vera). Evidence supporting 2 populations of erythroid stem cells in the bone marrow].

In vitro studies using the plasma clot culture system have been performed in order to compare the red cell pregenitors able to rise to erythrocytic colonies in 7 days (CFUE) in the bone marrow of polycythemia vera (PV), secondary polycythemias and normal subjects. In PV but never in normal individuals or secondary polycythemias, the bone marrow cells producing erythroid colonies without addition of erythropoietin were found. The erythropoietin dose response curves in PV is biphasic with a plateau up to a concentration of erythropoietin of 0.02--0.05 i.U./ml followed by a near normal response to erythropoietin at higher doses. Thus our results demonstrate that two populations of erythroid stem cells coexist in PV, one being abnormally sensitive to (or independent of) erythropoietin, the other normally responding to erythropoietin. After remission induced by P32 treatment, the abnormal population can disappear but the prognostic significance of this disappearance is uncertain. In the whole these results are in agreement with those of others laboratories using the plasma clot culture system. The reasons of the disagreement with the data published using the methylcellulose technic of culture are discussed.

Cell Differentiation

[Aleukemic chloroma. review of literature and diagnostic problems: 1 case].

The authors report the case of a 30-year-old man with granulocytic sarcoma of the chest wall presenting as a swelling with axillary lymphadenopathy followed by pleuropericardial effusions. The myeloblastic nature of the tumor cells was confirmed on the adenogram by the detection of granulations, rare Auer bodies and myeloperoxydase activity. It was confirmed by the presence of numerous granulations by electron microscopy and by that of a chloracetate esterase activity detected using Leder's protocol (9) on sections of material mounted in paraffin wax after formol fixation. Four marrow biopsies form different sites were normal. The course was fatal in six months, despite multiple chemotherapy, with massive invasion of the thorax by the tumor without the presence of myeloblasts in the circulating blood. The autopsy confirmed the preponderance of thoracic involvement (greenish in colour) and the presence of diffuse marrow myeloblastosis. In the light of this case, the rare instances (of the order of 10) of aleukaemic chloroma recorded in the literature are reviewed, emphasising the difficulties of diagnosis of these tumours and the ways in which they may be overcome.

Adult

[Abnormal sensitivity to erythropoietin in the erythroblast precursors in Vaquez disease].

Marrow specimens of patients with polycythemia vera rise to erythrocytic colonies in vitro without addition of erythropoietin to the culture. This behavior was never observed with marrow cells of normal subjects or secondary erythrocytosis. These results indicate that the sensitivity of some erythrocytic progenitor cells to erythropoietin is altered in polycythemia vera.

Bone Marrow

Genetic control of antinuclear antibodies in mice infected with Rauscher leukemia virus.

The incidence of antinuclear antibodies after Rauscher leukemia virus inoculation was found to be significantly higher in C57BL/6 than in BALB/c mice and still greater in their F1 hybrids. The relationships among antinuclear antibody incidence, erythroblastic disease, Rauscher leukemia virus production, and the H-2 genotypes were studied in the F1 generation and backcrosses using different virus inocula. The results observed suggest that (a) at least two genes are involved in the control of susceptibility to Rauscher leukemia virus-induced erythroblastosis, one of them probably being H-2 linked, and that (b) a non-H-2-linked gene seems to control, at the same time, induction of antinuclear antibodies, focus-forming virus production in the spleen, and susceptibility to the disease. It can be concluded that C-type viruses play an active role in antinuclear antibody induction.

Animals

An unusual case of leukemia with high fetal hemoglobin: demonstration of abnormal hemoglobin synthesis localized in a red cell clone.

A high level of fetal hemoglobin was found in an 8-yr-old boy without any hematologic disorders except for a moderate anemia. The absence of hemoglobin abnormalities in the parents led us to suspect a latent malignant disease that, on follow-up, was confirmed to be myelomonocytic leukemia. Hemoglobin biosynthetic studies provided evidence of unbalanced synthesis of globin subunits by reticulocytes, while the production of non-alpha chains was equal to that of alpha chains in bone marrow cells. The expression of red cell antigen i was increased, while those of I, A, and A1 antigens were found to decrease progressively. Two populations of erythrocytes, A-positive and A-negative, were distinguished and could be separated by differential agglutination. Unbalanced globin chain synthesis, increased fetal hemoglobin, and antigenic changes of the membrane were shown to be restricted to the A-negative population. The biologic data were not entirely consistent with a genuine reversion to fetal erythropoiesis. The question remains of a polychromosomal lesion of either quiescent F cells or adult stem cells.

ABO Blood-Group System

Enhancement of murine erythrocyte auto-antibody responses by Rauscher leukemogenic virus and by a weak allogeneic stimulation.

B6/c mice do not develop spontaneous positive direct Coomb's tests (DCT), but they are highly susceptible to the induction of erythrocyte auto-antibodies by immunization with cross reacting rat blood cells (36% positive DCT). Rauscher leukemogenic virus (RLV) does not directly induce DCT in these susceptible mice; neither does the inoculation of parental spleen cells. On the other hand both RLV and allogeneic stimulation by parental spleen cells enhance the incidence of the rat blood cell-induced DCT (up to 75% and 69% respectively). This is discussed in terms of a separate etiology to antinuclear and anti-erythrocyte auto-antibodies and of the possible mechanisms of auto-immune stimulation by oncogenic viruses or allogeneic stimulation.

Animals