PubMed Health⌕ Search

Biomedical subjects

B Lartigue

Publications and source records attributed to B Lartigue.

6 recordsLinked to original sources

[Evaluation of multidrug resistance phenotype on medullary specimens from patients with acute leukemia by determination of nuclear efflux of tetrahydropyranyl-doxorubicin. Approach by confocal laser microspectrofluorometry].

Confocal microspectrofluorometry allows the analysis of fluorescent molecules such as anthracylines in isolated living cells. An optical microscope fitted with a phase-contrast 100 X water-immersion objective enables simultaneous observation of the sample, focusing of the laser beam on the selected cell fraction (nucleus) and collection of the fluorescence emitted from the sample. The resulting intranuclear spectra are interpreted according to a quantitative model of the fluorescence spectra of both free and DNA-bound anthracycline. The intranuclear drug concentration can thus be determined. This technique has been applied to blast cells collected in patients with acute leukemia. Leukemic cells are aspirated from bone marrow, separated by Ficoll sedimentation and resuspended in RPMI-1640 containing 10% fetal calf serum and 200 nM tetrahydropyranyl-doxorubicin (THP-DOX). After one hour, 20 cells are analyzed and the mean nuclear drug content is determined (C1). Cells are then resuspended in the same medium but without anthracycline for 3 hours and the mean intranuclear drug concentration is then also determined (C3). From C1 and C3 the retention rate (RR) is calculated. Firstly, the accuracy of the method was checked. In 4 AML patients, two different samples aspirated on the same day were divided into two portions. Thus, two measurements were made on each one (4 values per patient). Coefficients of variation were satisfactory (4, 6, 12, and 12%). Secondly, blast cells collected in patients with AML and ALL at diagnosis or in relapse were studied. P-glycoprotein (P-gp) and CD34 expression was also studied using respectively immunohistochemistry land flow cytometry. Results obtained from the first 21 patients showed that there was no correlation between RR and either P-gp or CD34 expression. This could result from the efflux of THP-DOX by other mechanisms and/or low sensitivity of the staining technique.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

In vitro study of THP-doxorubicin retention in human leukemic cells using confocal laser microspectrofluorometry.

Microspectrofluorometry allows the analysis of fluorescent molecules such as anthracyclines in the nucleus of isolated living cells. Using this technique, we confirmed that the amount of doxorubicin or THP-doxorubicin incorporated into the nucleus was related to the resistant or sensitive character of K562 cells. It was then extended to the study of fresh leukemic cells and kinetic studies were performed allowing the calculation of the retention rate (RR) of anthracycline (THP-doxorubicin) into the cell nucleus. A reproducibility study confirmed the accuracy of the method. Blast cells collected in patients with acute myeloid (n = 22) or lymphoid (n = 8) leukemia, at diagnosis (n = 26), or in relapse (n = 4) have been studied. RR varied from 8 to 98% independently of the type of leukemia or the clinical status. RR did not correlate either with P-glycoprotein or with CD34 expression although this latter result should be confirmed on a higher number of subjects. Among 18 patients presenting with AML at diagnosis, 14 have been treated with intensive chemotherapy including anthracyclines; the only one who had resistant disease had the lowest RR value. In conclusion, the results obtained here show that microspectrofluorometry allows the performance of kinetic studies on fresh leukemic cells in order to quantify chemo-resistance phenomena related to drug transport.

Biological Transport↗

[Hemorheologic changes in preoperative hemodilution during total hip replacement. Randomized study comparing hydroxyethyl starch 200,000/0.62 (HES) and a dextran 60,000].

Hemodilution can be used to save blood transfusion during total hip replacement. We have carried out a randomized study to compare the hemorheological effects of two plasma substitutes: a hydroxyethylstarch 200,000/0.62 versus a dextran 60,000. Twenty-two patients were hemodiluted with 20 mk/kg of either substitute, just after the spinal anesthesia. Whereas the hematocrit have fallen by 30% in the two groups, significant differences are observed about hemorheological parameters. The plasma viscosity express a greater increase at hour 4 in the dextran group. The whole blood viscosities are more increased in the dextran group at hour 4 and 24. The erythrocyte aggregation is decreased in the HES group at hour 4 and 24, but is increased in the dextran group. The fibrinogen is more increased in the dextran group at day 7. In spite of similar hemodilutions, the two substitutes express different hemorheological effects with a favourable role of HES on erythrocyte aggregation and blood viscosities. This can improve the microcirculation and decrease the activation of the endothelial cells, reducing the inflammatory reaction.

Adult↗

Erythrocyte aggregation--determination of normal values. Influence of age, sex, hormonal state, oestroprogestative treatment, haematological parameters and cigarette smoking.

Erythrocyte aggregation is a physiological phenomenon and constitutes one of the most important factors accounting for the non-Newtonian properties of normal human blood. Pathological aspects have also been described and therapy aimed at reducing hyperaggregability has been proposed. The object of this study was to establish normal values of erythrocyte aggregation parameters as measured by laser light backscattering and to study the influence of various physiological factors. Normal values were determined from a reference population. Sex and age induce variations in erythrocyte aggregation which are neither fibrinogen nor haematocrit dependent and there is a general trend towards stronger aggregation in women, although neither hormonal state nor oestroprogestative treatment appear to influence the female aggregation parameters. In elderly people stronger aggregation is also observed but this effect is of lower magnitude. In vivo, the plasma fibrinogen level is the most important factor influencing erythrocyte aggregation, while variations in haematocrit play a lesser role and mean corpuscular volume, red cell distribution width and white blood cell and platelet counts have no effect. Finally, no difference is noted in cigarette smokers.

Adolescent↗

Evaluation of the efficacy of prophylactic intravenous antibiotherapy with ceftriaxone in post-chemotherapy agranulocytic patients.

A prospective study was carried out in 44 patients treated by intensive chemotherapy inducing a prolonged neutropenia (granulocytes less than 0.5.10(9)/l). All the patients were isolated in protected rooms, received a pathogen-free diet and nonabsorbable oral antibiotics. After double-blind randomization, 22 patients received 2 g of Ceftriaxone (Cef) in a daily infusion beginning on the first day of chemotherapy; and 22 patients received 2 g of placebo (P) under the same conditions. Prophylaxis was continued until the neutropenia resolved (granulocytes greater than 0.5.10(9)/l) or until the onset of infectious symptoms. 19 patients in each group developed febrile episodes, occurring significantly later in the Cef group (16.6 days versus 10.6 days in the P group). No Cef-resistant organism was isolated. Finally, the time at which apyrexia was obtained after the beginning of curative antibiotherapy was the same in both groups. The routine intravenous administration of Cef in combination with nonabsorbable antibiotics is a useful approach in reducing the risk of infection in the neutropenic host.

Adult↗