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Biomedical subjects

Y Najean

Publications and source records attributed to Y Najean.

At least 127 records · Page 7Linked to original sources

[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↗

The clinical significance of beta-thromboglobulin and platelet factor-4 in polycythaemic patients.

Simultaneous assays of platelet factor 4 (PF-4) and beta-thromboglobulin (beta TG) were performed in 192 cases of myeloproliferative syndromes (polycythaemia vera and primary thrombocytosis, as defined by the Polycythaemia Vera Study Group). The results led to the following conclusions: (I) both assays must be combined in order to avoid a poor interpretation due to marker release in vitro; (II) the 'normality' of the values must take the platelet number into account, even in the 'normal' range of this parameter; (III) the sensitivity of the beta TG assay is greater than that of PF-4 when considering the correlation of the marker values with arterial accidents; (IV) the predictive value of an excessive level of beta TG and/or PF-4 is difficult to define, since only 13 of the cases studied had a vascular accident during the 12-month follow-up period, and the levels of the markers in these patients were not statistically different from the levels in those patients not experiencing such accidents.

Adult↗

Partial purification of a thrombocytopoiesis stimulating factor present in the serum of thrombocytopenic rats.

Successive chromatographic procedures made it possible to isolate thrombocytopoietin from the serum of thrombocytopenic rats. The following steps were taken: DEAE-cellulose phosphate chromatography, Sephadex chromatography, exclusion chromatography on DEAE-Sephadex A-50 gel. The apparent molecular weight of thrombocytopoietin was about 48,000 daltons. Like erythropoietin, thrombocytopoietin is a glycoprotein, its molecular weight is similar. A single form is obtained only when the different purification steps last less than 10 days. Beyond that time, partial degradation may occur.

Animals↗

[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↗

[Use of radioactive isotopes in clinical hematology].

Principles underlying the use of radioactive isotopes for diagnostic, prognostic, and therapeutic purposes in human biology are briefly discussed, and the possibilities of the employ of isotopic techniques in general illustrated by the results obtained in human hematology.

Blood Cells↗

[Analysis of various isoferritins with monoclonal antibodies].

Balb/c Mice were immunized with splenic isoferritin. Spleen cells from immunized Mice were fuzed with SP2O myeloma cells. Four monoclonal antibodies designated respectively M29, M211, M386 and B8 were selected. Various isoferritins were analysed by immunodiffusion (Ouchterlony technic). With these monoclonal antibodies and with Rabbit polyclonal sera: human basic and acidic isoferritins and Horse spleen ferritin. Ferritin could be precipitated by these monoclonal antibodies. These results confirm that the ferritin molecule consists of repeating antigenic sites. No immunoreactivity difference could be detected between acidic and basic human ferritine. Species specificity was recognized. The high affinity constant of the M29 monoclonal antibody allowed development of a standardized radioimmunossay of ferritin.

Animals↗

Effect of combination chemotherapy, duration of methotrexate administration, and patient's age on methotrexate pharmacokinetics.

The kinetics of methotrexate were studied in a group of 59 patients after infusion of high doses. From the triexponential analysis of the serum concentration curve, rate constants and relative concentrations in non-circulating pools were calculated, using a linear 'mammillary' three-compartment model. No significant variation as a function of dose (300-6,000 mg/m2) was observed. In circumstances the rapidly exchanging pool was a reflection of the circulating pool, suggesting that it is an extravascular, protein-bound pool of methotrexate. Considerable variations of the relative concentration and rate constants of the slowly exchanging pool were observed to be a function of the duration of methotrexate infusion, the presence of other drugs, and the patient's age. If this compartment is assumed to include the target cells for methotrexate, then the large variations observed could be responsible for individual differences in toxicity and/or effectiveness.

Acute Disease↗

Gastric emptying and intragastric distribution of lipids in man. A new scintigraphic method of study.

We measured gastric emptying of fat and water from a solid-liquid meal in healthy volunteers using a tubeless scintigraphic method. Selenium-75 glycerol triether, incorporated in butter, was the lipid-phase marker, and technetium-99m, ingested with 250 ml water, the non-lipid phase marker. In seven of these subjects we also measured the gastric emptying of solids and liquids with technetium-99m bound to cooked egg whites as the solid-phase marker and indium-111 ingested with 250 ml water as the marker of the solid and aqueous phases. Emptying and intragastric repartition of each marker were measured by detection of radioactivity changes over the abdominal area using a gamma-camera. The stability and the specificity of the labeling was checked for each marker. Mean gastric emptying rate (expressed as percentage ingested marker emptied per hr) of lipids (17.4 +/- 2.4) was much lower than that of the rest of the meal (34.2 +/- 1.8) and slightly, but significantly, lower than that of solids (22.8 +/- 1.8). An intragastric layering of fat above nonlipids was observed only after the first postprandial hour and remained moderate. Thus, lipids are emptied more slowly than any other component of an ordinary meal, and this is not due only to layering of fat above water.

Adult↗

Two different in vitro growth patterns for erythroid precursors in 18 patients with pure erythrocytosis.

Growth patterns of marrow and blood erythroid progenitors were studied in 18 cases of pure erythrocytosis using different doses of erythropoietin. 8 cases demonstrated 'spontaneous' growth of CFU-E and blood BFU-E as observed in myeloproliferative disorders, but without an excess of circulating CFU-GM. 3 of these patients also had other symptoms of a pan-myelopathy. All these cases showed good sensitivity to 32P myelo-suppression. 10 cases demonstrated growth patterns of erythroid progenitors similar to those observed in normal subjects, except for an excess of blood BFU-E, which suggests an abnormality of homeostatic regulation. In 5 of these cases, myelo-suppression was not effective. It is suggested that a stem cell study could differentiate patients with pure erythrocytosis due to 'autonomous' abnormal stem cell growth from cases due to abnormal regulation factors, and that such a discrimination might be useful for the choice of therapy.

Cells, Cultured↗

Prognostic factors and evolution of acquired aplastic anemia in childhood. A prospective analysis of 48 androgen-treated cases.

Forty-eight cases of acquired aplastic anemia in children were analyzed in comparison to 26 cases of genetic aplastic anemia and 483 cases of aplastic anemia in adults. All were gathered from similar institutions and all were similarly followed and treated with androgens. The following conclusions were drawn: 1) Initial severity is greater in children than in adults, and is greater in acquired than in genetic aplastic anemia; 2) even in cases of similar initial severity, the early death rate is higher in children than in adults; 3) a multiparametric index allows the correct prediction of short-term evolution in 70% of the cases and thus aids in providing an indication for bone marrow graft; its sensitivity is similar to that of the classical parameters proposed by Camitta, et al., but its specificity significantly higher; 4) most deaths occurred during the first 3-4 months and the chance for long-term improvement appears similar in the more severe than in the less severe cases if they survive this delay; 5) some data (relapse after androgen withdrawal and androgen-dependence and failure of corticoid therapy alone) suggest that androgen therapy in children is useful, as it is in adults, and that corticosteroids do not modify the course of the disease at its usual dosage (1 mg/kg/day); and 6) very few side effects, particularly concerning height, of androgens were noted in the survivors at adult age after long-term androgen therapy prescribed before puberty.

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↗