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Biomedical subjects

C Dresch

Publications and source records attributed to C Dresch.

At least 37 records · Page 2Linked to original sources

Chromosome studies in polycythemia vera patients.

One hundred thirty-five polycythemia vera (PV) patients (30 untreated by chemotherapy and 105 treated) were studied cytogenetically . The incidence of clonal chromosomal abnormalities was 20.7% (28 patients in nonleukemic phase). The incidence of 20q - was 3.7% (5 patients). The presence of cytogenetically abnormal clones did not allow prediction of the evolution of the disease. In a few cases, abnormal clones disappeared at the time of later studies. Although nonrandom, the majority of clonal chromosomal abnormalities are believed to be secondary events in PV patients.

Aged↗

The 'spent' phase of polycythaemia vera: hypersplenism in the absence of myelofibrosis.

A clinical phase (spent phase) in the course of polycythaemia vera (PV) cases is described as enlargement of the spleen in spite of treatment, frequent cytopenia of one or several lines, persistent red cell hypervolaemia with considerable increase of plasma volume, persistence of myeloid hyperplasia with no collagen myelofibrosis or osteomyelosclerosis, absence of hepatosplenic erythroblastic metaplasia, as shown by radio-iron kinetics and/or 111In-transferrin scintigraphy. The frequency of this phase was 5% in a study where it was not systematically sought, but it could in fact be greater. Its occurrence is not related to the clinical and biological parameters of PV. On the other hand, it is significantly more frequent and earlier in patients treated by phlebotomies than in those treated by myelosuppression (32P). In four of the 12 cases, this phase was rapidly followed by an acute leukaemia. In eight cases there was a 1-5 year interval before a myelofibrosis with splenic myeloid metaplasia. This evolution could at this stage be delayed by chemotherapy. The efficacy of splenectomy should be studied.

Aged↗

In vivo protection of normal mouse hematopoiesis by a beta 2 blocking agent during S-phase chemotherapy.

Butoxamine, a beta 2-adrenergic blocking agent, which temporarily blocks the G1-S transition of human bone marrow granulocyte precursors in vitro, was used in vivo together with 1-beta-D-arabinofuranosylcytosine (ara-C) in mice. Butoxamine alone depressed the granulocyte labeling index and granulocyte-monocyte colony-forming Cell (GM-CFC) suicide rate at a dose of 3 micrograms/g body weight. A maximum effect was produced 6 to 12 hr after injection. Butoxamine administered 8 hr before an injection of ara-C modified the proportion of GM-CFC in S phase as compared with the number found after ara-C alone. After a series of five ara-C injections, administered at intervals of 16 hr, 70% of the treated mice died within 2 weeks, whereas only 42% of mice pretreated with butoxamine 7 to 9 hr before each ara-C injection died. This difference was due to the more rapid return to normal of GM-CFC numbers and an increase in the proportion of GM-CFC and granulocyte precursors in S phase in the butoxamine-pretreated animals. These findings suggest that butoxamine may have a potential use in protecting hematopoiesis during intensive chemotherapy for cancer.

Adrenergic beta-Antagonists↗

In vitro bone marrow GM-CFC growth in aplastic patients. Correlation between E rosette forming cells and immunotherapy results.

In vitro bone marrow GM-CFC (granulomonocyte colony forming cell) growth following E rosette (+) cell depletion was studied in 14 aplastic patients to determine whether an autoimmune factor could be involved in the pathophysiological process leading to the decrease in bone marrow colony formation. The increase in GM-CFC growth after E rosette (+) cell depletion was high in 8 cases, suggesting that in these cases an autoimmune mechanism may have been involved. All these patients responded within a month to treatment with antithymocyte globulin (ATG) or corticosteroids. Six patients did not respond to immunotherapy, none showed increased GM-CFC growth. The increase of in vitro GM-CFC growth after E rosette (+) cell depletion in aplastic anemia could therefore be a good indication for the trial of immunotherapy. However this study seems to be useful only in patients with at least a few months evolution after diagnosis.

Adolescent↗

[Anemia in renal insufficiency. I--Mechanisms of anemia in patients treated with periodic hemodialysis].

Fifty-two patients with anaemia due to chronic renal insufficiency treated by haemodialysis were divided into three severity groups. Except for bi-nephrectomized patients, none of the usual criteria such as age, sex, cause of the renal disease and duration of dialysis correlated with clinical severity. Kinetic studies showed that the severity of anaemia was unrelated to the degree of haemolysis, haemoglobin function or haemodilution. Stem cells were increased in all cases, irrespective of clinical severity. However, the degree of anaemia closely correlated with the degree of erythropoietic deficiency, as measured by radio-iron kinetics. A qualitative defect (slow release of labelled cells from the bone marrow) was associated with severe quantitative erythroid defect. These data indicate that kinetic studies of erythropoiesis constitute objective methods for measuring clinical severity. They favour the theory which makes a hypothetical inhibitor of differentiation and/or proliferation of erythropoietic precursors the main cause of anaemia.

Anemia↗

Prognostic value of the combined suicide level of granulocyte progenitors and the labelling index of precursors in preleukemic states and oligoblastic leukemias.

Although abnormalities in granulopoiesis detected by means of bone marrow cytology, culture and kinetic studies have provided prognostic data in preleukemic states and oligoblastic leukemias, this information cannot be applied to individual cases. In order to determine the indications for treatment and the form it should take in a given case, data would be required concerning the probability of impending transformation into acute leukemia. In 45 studies involving 34 patients who were followed for 10-42 months, a combination of a rise in the proportion of granulocyte precursors in S-phase, indicated by a colony-forming cell suicide rate of over 40%, and a low labelling index of myeloblasts and promyelocytes, was always followed by the onset of acute leukemia within 10 months. Sequential studies in 13 patients revealed an increase in cluster-forming cells and in the suicide level in the second study. The changed kinetics of granulopoietic proliferation may provide an indication for chemotherapy.

Cell Division↗

[Vascular complications of polycythemia].

The vascular risk factors of patients with polycythemia rubra vera was assessed by reviewing the results of international therapeutic studies. The risk factors were: an age over 60, previous vascular problems, the quality of follow-up (maintenance of hematocrit below 50 p. cent and platelet count below (600.10(9)/l). The treatment is one of the most important factors: the risk of vascular complications was three times greater in patients treated by venesection, al other factors being equal. This counter-balanced the higher risk of leukemia in patients treated by myelo-depression. The use of platelet anti-agregant drugs remains controversial. Recent results question their efficacy in preventing thrombosis and emphasise the risk of hemorrhage. The results of platelet factor 4 (PF4) and beta-thromboglobin (beta TG) levels provide further information for judging the vascular risk of these patients, and may, in prospective studies, give a better assessment of the efficacy of platelet anti-agregant drugs in vivo.

Follow-Up Studies↗

Cytosine arabinoside as a suicide agent for human colony forming cells.

The fractional reduction of cloning efficiency, otherwise known as in vitro suicide, produced by HU or 3H-TdR, is considered equivalent to the fraction of colony forming cells (CFC) in S phase and is used for the evaluation of proliferation in this population. The accuracy of both agents has been discussed. We tested cytosine arabinoside (Ara-C) on normal and pathological human bone marrow GM-CFC on different parameters. A plateau of concentrations between 1 and 5 X 10(-6) M was found to be as effective as 3H-TdR in diminishing 7 to 9 day colonies. Ara-C solutions were equally effective up to 18 weeks of storage at 4 degrees C; suicide levels were unchanged between 2 X 10(5) and 5 X 10(6) cells/ml; incubation with Ara-C was not critical between 1 and 2 h. Unlike HU, Ara-C does not require strict conditions of cell concentration, incubation time or extemporaneous preparation. Compared with 3H-TdR, Ara-C is easy to handle and does not show a decrease in cell cloning with the duration of the culture suggesting a prolonged action of the drug. Results on cell killing are comparable with the three drugs on day 7 to 9 colonies and we conclude that Ara-C is a reliable agent for suicide studies on human bone marrow GM-CFC.

Bone Marrow Cells↗

[Mechanisms and prognosis of neutropenia in Felty's syndrome. 27 cases (author's transl)].

Twenty patients with Felty's syndrome were investigated. Isotopic studies of polymorphonuclear neutrophils, bone marrow biopsies and autoradiographies, and cultures of granulous stem cells showed that neutropenia resulted from three mechanisms acting simultaneously: hypermargination of the neutrophils predominantly in the spleen, decreased production of granulocytes in the bone marrow, and peripheral hyperdestruction of the neutrophils. Anti-granulocyte antibodies were detected in 3/12 patients. Other factors present in the serum of 2/4 patients seem capable of inhibiting the growth of granulocytic stem cells. Secondary bacterial infection (77%) may explain the severity of the prognosis: 13 out of 27 patients died 4 years on average after neutropenia was diagnosed.

Agranulocytosis↗

Inhibitory effects of peripheral blood cells on in vitro colony formation by autologous bone marrow in aplastic anaemia: relation with response to immunosuppressive therapy.

The inhibitory activity of peripheral blood lymphocytes on autologous bone marrow was studied in 27 patients with aplastic anaemia after treatment with androgen. Inhibitory activity was hard to assess in 10 patients studied during the first year of treatment. The colony count was too low to be certain of differences between the samples incubated with or without lymphocytes. Among the 17 patients who had more than 10 colonies per 2 x 10(5) mononuclear bone marrow cells, nine showed inhibitory activity by peripheral blood lymphocytes. After 12 months of androgen therapy each of these patients showing inhibitory activity of bone marrow colony forming cells by peripheral lymphocytes responded to antithymocyte globulin. None of nine patients with few colony forming cells or no inhibitory activity of lymphocytes responded to immunosuppression.

Adolescent↗

The use of cimetidine for the treatment of pruritus in polycythemia vera.

Thirty-four patients with polycythemia vera complicated by pruritus were treated with 900 mg of cimetidine daily for 30 days and their responses to treatment were evaluated. The conditions of 15 (44%) were improved, with 12 patients stating that pruritus completely disappeared. Nineteen patients either showed no improvement or had increasing symptoms. No toxic effects were reported. The positive responses seen are encouraging and suggest that controlled studies are indicated to further evaluate the effectiveness of H2 antagonists.

Cimetidine↗

Pure erythrocytosis: reappraisal of a study of 51 cases.

Fifty-one cases of pure, primary erythrocytosis were identified and followed at Hôpital Saint-Louis, Paris, and compared with 350 cases of polycythemia vera (PV) observed during the same period. At the initial evaluation, these cases did not differ from PV cases with respect to age, sex ratio, degree of red cell volume increase, and clinical symptoms. They did differ by the absence of splenomegaly, granulocytosis and thrombocytosis. At a late stage of evolution only a few cases developed classical criteria of PV. From this group of apparently homogeneous cases, two subgroups evolved. Sixty percent of the cases were highly responsive to myelosuppression with 32P. The median duration of the first remission was greater than five years, the mean yearly dose of 32P was very low, and there was a low incidence of complications. The other group (40% of cases) was relatively resistant to myelosuppressive agents. The development of better methods of investigate this disorder might help in discriminating these two groups from both an etiological and pathophysiological viewpoint. The thromboembolic risk of these diseases suggests that myelosuppressive therapy should be utilized in older patients with higher risk of vascular accidents, reserving phlebotomy for younger patients and those who are shown to be resistant to 32P therapy.

Adolescent↗

Granulocyte progenitor compartments after allogeneic bone marrow grafts.

Bone marrow granulocyte colony forming cells (CFU-C) were measured in HLA compatible sibling donor-recipient pairs. The regeneration of granulocytes and CFU-C compartments were also studied in order to evaluate haemopoietic recovery. The number of nucleated bone marrow cells in the donation was 23 +/- 4 X 10 cells, which recipients received (3.5 +/- 0.4) X 10(8) nucleated cells/kg and (1.19 +/- 0.32) X 10(5) CFU-C/kg. This produced a bone marrow reconstitution of (67 +/- 26) X 10(5) CFU-C/kg by day 30. There was a significant correlation between CFU-C/kg and (1) granulocyte count on day 30 (P equal less than 0.05) and (2) the first day of reappearance of neutrophils in the blood (P equal less than 0.05). These results indicate that the speed and completeness of granulocyte regeneration can be predicted by measurement of the size of the CFU-C inoculant in the bone marrow graft.

Adolescent↗

Effect of beta adrenergic agonists and beta blocking agents on hemopoiesis in human bone marrow.

The effect of propranolol (non specific blocking agent), acebutolol (beta 1 blocking agent), butoxamine (beta 2 blocking agent) and several beta adrenergic agonists was studied on 3H-thymidine (3H-TdR) incorporation and granulo-monocyte colony formation in agar by human bone marrow. Only butoxamine and propranolol decreased 3H-TdR incorporation by total normal bone marrow cells at concentrations above 10(-6) M for butoxamine and 10(-5) M for propranolol. Autoradiography showed that inhibition of 3H-TdR incorporation by butoxamine was slightly more pronounced on neutrophil precursors than on red cell precursors (neutrophil series LI..53 and erythroblasts .67 compared to control bone marrow cells at 10(-5) M concentration). The development of granulo-monocyte colonies in agar culture was delayed by preincubation with butoxamine at concentrations above 5 X 10(-6) M. Hydroxyurea suicide showed that this was due to a decrease in the number of CFU-C in S phase. beta 2 blocking agents are able to decrease the number of normal hematopoietic cells entering S phase. This effect is seen on both neutrophil and erythroblastic precursors and on granulo-monocyte progenitors. It could be used as a means of protecting bone marrow cells during cancer intensive chemotherapy.

Adrenergic beta-Agonists↗