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Biomedical subjects

G Meuret

Publications and source records attributed to G Meuret.

At least 55 records · Page 3Linked to original sources

Monocyte recruitment in tuberculosis and sarcoidosis.

Monocytopoiesis and blood monocytes were investigated in nine patients with active tuberculosis and in six patients with active sarcoidosis in order to obtain information on monocyte consumption in these two types of granuloma. All patients with tuberculosis demonstrated a marked increase in proliferation activity of monocytopoiesis and premature monocyte marrow release. These changes indicate a high monocyte consumption which probably is caused by a high macrophage death rate due to the high macrophage-toxicity of tubercle bacilli. Thus, tuberculous lesions are an example of a "high turnover granuloma". In sarcoidosis monocytopoiesis showed no significant deviations from the normal. This indicates a low macrophage turnover or "low turnover granuloma". Thus, any hypothetical agent assumed to be involved in the pathogenesis of sarcoidosis would have to possess low macrophage-toxicity.

Adolescent↗

Transferrin-immune complex disease.

A 71-year-old woman showed a highly unusual pattern of iron distribution in the organism which was associated with iron overload. The hallmark of this disease was an extreme hypersiderinemia, the serum iron reaching about 800 mug/100 ml. There was a pigment cirrhosis of the liver, bronzed skin containing hemosiderin, and diabetes mellitus. Paradoxically, hemosiderin was not detectable in bone marrow macrophages, sideroblasts and erythrocytes were reduced, and there was a decrease in radioiron utilization of erythropoiesis, thus indicating insufficient iron supply. The pathogenesis of this disorder based on the formation of an autoantibody with specificity for transferrin thus producing a circulating immune complex which bound the majority of serum iron. Immunosuppression achieved a partial remission including a recovery of the patient's general state, a rise in free transferrin, a decrease in serum iron, disappearance of hemosiderin in the liver, and a rise in erythrocyte production.

Aged↗

[Rotor syndrome. A long-term study].

A patient with Rotor syndrome has been followed up for 28 years. The subject was in good health and exhibited marked jaundice due to a hyperbilirubinemia ranging between 5 and 8 mg bilirubin per 100 ml, about 70% of the bilirubin giving direct van den Berg reaction. The liver was slightly enlarged and of normal color. Histologically it showed traces of a brown pigment and marked siderosis in the hepatocytes. In addition, mild hypersideremia and hypercholesteremia were observed together with increased amounts of bilirubin and urobilinogen in urine. Menthol glucuronide formation was normal. Hepatic excretion of bilirubin, sulfobromophthalein and radio-opaque dyes was impaired. There was no change in liver histology of biopsies taken at an interval of 6 years, the siderosis in particular remaining constant. During the observation a moderate increase in the activities of serum transaminases occurred but no longer recurred when physical and dietetic stress was avoided.

Adult↗

[Harvesting of granulocytes for granulocyte transfusion by means of continuous flow centrifugation or filtration leukapheresis].

More than 10(10) viable granulocytes are necessary for a therapeutical effective granulocyte transfusion. This number of cells can be harvested from normal donors by two techniques basing on different principles: continuous flow centrifugation (CFC) and filtration leucapheresis (FL). Our studies demonstrated that, under certain special conditions, the separation potentials of both methods are comparable yielding 2.5 to 3.0 X 10(10) granulocytes within 4 hrs. Granulocyte collection rate was optimal if donors were treated with dexamethasone during 16 hrs prior to the state of the procedure. However, the costs of CFC exceed those of FL by a factor of about two. The increased occurrence of side effects attributed to the transfusion of FL-granulocytes can be reduced to the level of CFC-granulocytes by repetitive filtration-elution leucapheresis minimizing cell damage. The studies define the efficiency spectrum of CFC which in addition to granulocyte separation includes collection of thrombocytes, cells for immunotherapy, and plasmapheresis.

Blood Transfusion↗

Neutrophil marrow release. A system analysis.

Neutrophil marrow egress is governed by several processes. The most important are cell maturation, functional behavior of marrow sinusoids and humoral or neuro-vascular factors. Neutrophil release cannot be observed directly but is reflected in the size, cellular composition and kinetics of the nonproliferating pool of granulocytopoiesis in bone marrow and of blood neutrophil pool. These experimentally determined parameters were used as the basis of a mathematical model study. The model describes two catenated compartments, the nonproliferating pool of granulocytopoiesis in marrow and the total blood granulocyte pool. Cell transit from one pool to the other was assumed to be age-dependent. It was expressed by a positive sloping sigmoidal function that defines the egress potential fo the cells that increases with cell maturation. During maturation granulocytopoietic cells develop intense motility which determines the morphology of the cells on smears. Relationship between cell motility and its morphology was defined by functions determining the age-dependent probabilities of cell fixation as metamyelocytes, band- and segmented forms, respectively. The parameters of this model could be so adjusted that all experimental data were matched within experimental errors. Thus, qualitative and quantitative information on neutrophil marrow egress was obtained for normal and pathological states of granulocytopoiesis.

Age Factors↗

Monocytopoiesis in chronic eczematous diseases, psoriasis vulgaris, and mycosis fungoides.

Monocytopoiesis and blood monocytes were examined in 8 patients with disseminated chronic eczematous diseases, 8 patients with disseminated psoriasis vulgaris, and 8 patients with mycosis fungoides in plaque or tumor stage. Monocytopoiesis was moderately stimulated in all these patients. The stimulation manifested itself by: (1) a rise in relative number of promonocytes in bone marrow in all patients with eczema, in 1 out of 8 patients with psoriasis, and in 7 out of 9 examinations in patients with mycosis fungoides; (2) a rise in [3H]thymidine labeling indices of medullar promonocytes (8/8 eczema, 7/7 psoriasis, 8/9 mycosis fungoides); and (3) a rise in the naphthol-AS-D-chloroacetate esterase activity of blood monocytes, indicating premature monocyte marrow egress (3/5 eczema, 7/8 psoriasis, 9/9 mycosis fungoides). In eczema and psoriasis the mean enhancement of monocytopoietic activity was similar but less pronounced than in mycosis fungoides. In the latter disease there was no correlation between measured parameters and visible skin lesions. The results were interpreted as indicative of increased monocyte consumption by pathologic, immunologic, and/or inflammatory processes.

Adult↗

Intravascular fate of granulocytes administered by granujlocyte transfusions.

Granulocytes were harvested from hematologically normal individuals using continuous flow centrifugation (CFC) or filtration leukapheresis (FL). The isolated granulocytes were labeled in vitro by 3H-diisopropyl fluorophosphate (3H-DFP) and autotransfused. Their intravascular fate was analyzed by autoradiography. Immediately after autotransfusion the majority of granulocytes administered, collected in the marginal granulocyte pool. Margination was particularly prominent in granulocytes isolated by FL. The distribution of transfused granulocytes between the circulating and the marginal granulocyte pool showed wide and irregular fluctuations in time. Margination of transfused granulocytes was counterbalanced, and its fluctuation between the two intravascular pools was stabilized by prednisone treatment. The transit of transfused granulocytes from blood to tissue seemed to be governed by a random process, the half-disappearance time being either normal or prolonged. Compatible granulocytes administered to hematologically normal recipients circulated for at least 20 h.

Blood Transfusion, Autologous↗

[Anemia in terminal kidney insufficiency: ferrokinetics, erythrocyte survival times and erythrocyte enzymes in chronic dialysis patients].

Radio-iron utilization was nearly normal in these patients, only bilateral nephrectomized patients showed a reduced radio-iron utilization. Red blood half-life span was shortened in all patients, well corresponding to the degree of anemia. Parameters of erythropoesis like plasma iron clearance, bone marrow transit time, erythron iron turnover, non erythron iron turnover and hemolysis iron turnover failed to quantitate disorders of red blood cell regeneration in these patients. No defect in red blood cell enzyme activity could be demonstrated. Enzymes of glycolysis were increased corresponding to the reduced erythrocyte half-life span.

Anemia, Hemolytic↗

[Dyserythropoietic anemia, type I: ineffective erythropoiesis due to disorders in the DNA-nucleoprotein complex].

The relative DNA, RNA histone and hemoglobin contents and 3H-thymidine incorporation in vitro were determined sequentially in individual erythroblasts of type I dyserythropoietic anemia. The histone/DNA ratio was increased due to a rise in histone extinction, indicating a pathological DNA-nucleoprotein complex. In addition, the erythroblasts displayed an increase in DNA content exceeding tetraploid values, a loss of DNA-synthesis activity at immature stages with low hemoglobin content, and a reduction of RNA. These variations were assumed to be caused by the preceding and primary impairment of the DNA-nucleoprotein complex.

Adult↗

[Prevention of infection in patients with agranulocytosis through isolation and whole-body decontamination].

During induction chemotherapy 21 patients with acute myelogenous leukemia and agranulocytosis were prophylactically isolated either in reverse isolation (group A) or in sterile plastic-tent isolators with laminar air flow (Life Islands, group B). Patients of group B also received whole-body decontamination and sterile food. Life threatening septicemias were seen only in patients in reverse isolation. Granulocyte transfusions were highly successful in reducing infection-related mortality in group A. Seven additional patients with agranulocytosis of varying origin (group C) were protected in the Life Islands as effectively as the patients with acute leukemia.

Adolescent↗

Present status of 32P-therapy in management of polycythemia vera.

The aim of this study is to assess the present status of 32P-therapy in the management of polycythemia vera. The nature of the disease and its associated clinical problems was considered with respect to the characteristics of the different therapeutic approaches. We concluded that 32P is preferably administered to older patients, especially if long term remissions are achieved, if drugs are taken unreliably, or if patients are difficult to supervise. At present chemotherapy is preferably administered to younger patients, to those who respond inadequately to 32P, or who demonstrate early relapsing hyperproliferation of granulocytopoiesis, or who require 32P-administration at intervals shorter than one year.

Alkylating Agents↗

32P-therapy in polycythemia vera.

A group of 52 consecutive patients with polycythemia vera was submitted to long-term therapy with radioactive phosphorus (32P). Initial phase of therapy induced complete remissions (normalization of hematogram; spleen not palpable) in 45% of the patients, and partial remissions in the remaining 55%. During maintenance therapy of the complete remission group, mean remission time was about 3.5 years. Individual remission times ranged between 1 and 6 years. In the group of patients with incomplete remission, mean remission time increased with the progression of the disease due to gradual development of "spent" -polycythemia. In patients with splenomegaly, remission time was negatively correlated to spleen size. In both groups the increment of annual accumulated dose averaged 2.4 mCi 32P. When considering polycythemia related causes of death only, mean survival time attained 12 years after initial treatment with 32P. Acute leukemia occurred in 2 patients (4%).

Adult↗

Monocytopoiesis in normal man: pool size, proliferation activity and DNA synthesis time of promonocytes.

Monocytopoiesis was analyzed in the bone marrow of healthy individuals. Promonocytes were identified by simultaneous determination of sodium-fluoride-sensitive and resistent naphthol-AS-D-acetate esterases. DNA synthesis activity of enzyme-positive promocytes was determined by 3H-thymidine (3H-TDR) incorporation in vitro. DNA synthesis time of these cells was measured by a double labelling technique (3H-TDR in vivo, 14C-TDR in vitro) as well as by serial injections of 3H-TDR. The relative number of promonocytes in the myelogram averaged 2.9% corresponding to a medullar promonocyte pool of about 600 X 10(6) cells per kilogram body weight. The promonocytes were classified into 4 groups on the basis of nucleus morphology: type I promonocytes with small lymphocyte-like nuclei (mean frequency of occurence, F = 5%; mean 3H-TDR labelling index, LI = 7.1%; type II promonocytes with large round or oval nuclei (F = 31%; LI = 9.7%); type III promonocytes with large, slightly folded nuclei (F = 51%; LI = 10.1%); type IV promonocytes with large, distinctly folded nuclei (F = 13%; LI = 24.9%). LI of pooled promonocytes was 12.0%. Mean DNA synthesis times of the different types of promonocytes was similar and approximated 10 h (range 6.6-13.3 h). This was true under normal conditions as well as in septicaemia.

Adult↗

Human monocytopoiesis in acute and chronic inflammation.

Monocytopoiesis was analyzed in patients with severe, acute inflammations induced by surgical interventions as well as in others with mild, chronic inflammations in connection with gastric or duodenal ulcers. The state of acute inflammation was assumed to be associated with a high and steeply rising monocyte demand as opposed to the constant and relatively small monocyte recruitment in chronic inflammation. In chronic mild inflammatory reactions DNA synthesis activity of promonocytes was increased by a factor of about two; the promonocyte pool was normal. In patients who underwent surgical operations changes in the following parameters were observed during the first 15 h after start of surgery: (1) average increase in 3H-TDR labelling index by 38%; (2) average enlargement of promonocyte pool by 34%, (3) and relase of immature cells from the bone marrow into the blood. Increase in DNA synthesis activity as well as expansion of the promonocyte pool causes an enhanced monocyte production rate. The 'shift to the left' in monocyte egress is equivalent to a reduced stem-cell-to-blood transit time. These variations permit short-term adaptation of monocytopoiesis to varying demands.

Acute Disease↗