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Biomedical subjects

O Pradier

Publications and source records attributed to O Pradier.

At least 55 records · Page 3Linked to original sources
PubMed1996

Simplification of the blood stem cell transplantation (BSCT) procedure: large volume apheresis and uncontrolled rate cryopreservation at -80 degrees C.

Very high-dose chemotherapy with autologous blood stem cell (BSC) rescue becomes more and more widely performed. In order to simplify the technique, a large volume apheresis programme combined with an uncontrolled rate cryopreservation at -80 degrees C was developed. Twenty-six patients suffering from multiple myeloma (n = 8), non-Hodgkin's lymphoma (n = 7), dysgerminoma (n = 4), breast cancer (n = 3), Hodgkin's disease (n = 2), acute lymphoblastic leukaemia (n = 1) and acute myelocytic leukaemia (n = 1) were autografted after a classical high-dose chemotherapy regimen. A single large volume apheresis was sufficient to obtain the threshold value of CD34+ BSC in 24/26 transplantations. The haematological recovery was favourably comparable with the previously published data obtained with controlled rate frozen BSC: median time to granulocytes > 1000/microL and to a self-supporting platelet count > 20,000/microL, respectively, 10.5 and 12 d. The treatment-related mortality was confined to 1/26 BSCT. These results indicate that this easy and cost-saving policy of BSCT is efficacious and safe: sustained long-term haematopoiesis, reduced morbidity and mortality were observed.

Adult↗
PubMed1995

Comparative study of multidrug resistance evaluated by means of the quantitative immunohistochemical detection of P-glycoprotein and the functional release of rhodamine 123.

The immunological detection of P-Glycoprotein (P-GP) and the functional release of Rhodamine 123 (R123) have been compared in a number of human and murine cancer cell lines, in chemo- and/or radiotherapy-resistant subclones, and in clinical specimens from patients. The chemoresistance level was established from the viability index (IC50) in the presence of doxorubicin. Cytocentrifuge preparations were immunostained with JSB-1 monoclonal antibody followed by the alkaline phosphatase anti-alkaline phosphatase technique. The strength of the reaction was quantified by a digital image analyser. The kinetic incorporation and release of Rhodamine 123 were evaluated by flow cytometry. The parent cell lines and radiotherapy resistant subclones showed a low IC50, were JSB-1 negative and retained R123 during the whole experiment, while the chemoresistant and radio-chemoresistant cell line mutants had a high IC50, were JSB-1 positive, and actively pumped the R123 out of the cells. Good correlations were obtained between the IC50, the digital image analysis, and flow cytometry. The kinetic profile of the R123 release allowed the distinction between typical and atypical multidrug resistance phenotypes. These findings were confirmed in clinical specimens from patients. We conclude that antigenic and functional studies are complementary and are useful in experimental and clinical approaches to multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

A case of pleomorphic T-cell lymphoma with a high content of reactive histiocytes presented with hypereosinophilia.

A case of peripheral T-cell lymphoma classified, according to the updated Kiel classification, as a large pleomorphic T-cell lymphoma with a high content of reactive histiocytes and blood hypereosinophilia is reported. Light microscopic examination revealed a diffuse effacement of the lymph node structure by large pleomorphic lymphoma cells mixed with eosinophils and many histiocytes, some of them presenting discrete features of hemophagocytosis. The neoplastic cells were CD3, CD5, CD8 and HLA-DR positive but failed to show CD30 antigen. DNA molecular analysis displayed simultaneous rearrangements of the genes coding for the delta chain of the T-cell receptor and for the Ig heavy chain. Increased serum levels of angiotensin converting enzyme and ferritin were found and probably induced by the reactive histiocytes. Immunoassays (ELISA) with antibodies directed against some cytokines and against the Tac peptide (sIL-2R) were performed. They demonstrated high serum levels of sIL-2R and a slight increase in GM-CSF, but neither IL-5 nor IL-3. The association of blood hypereosinophilia and histiocytic hyperplasia with a peripheral T-cell lymphoma is discussed.

Adult↗
PubMed1995

Effects of aprotinin on blood loss, heparin monitoring tests, and heparin doses in patients undergoing coronary artery bypass surgery.

OBJECTIVES: Evaluation of the effect of aprotinin on heparin monitoring tests, on heparin doses, and on perioperative blood loss in patients undergoing coronary artery bypass grafting. DESIGN: Randomized, prospective open study. SETTING: The study was performed in the departments of Anaesthesiology and Haematology of the Erasme University Hospital, Brussels. PARTICIPANTS: Twenty-six patients undergoing primary coronary artery bypass grafting. INTERVENTIONS: Twelve patients received aprotinin, and 14 received no treatment. MEASUREMENT AND MAIN RESULTS: Aprotinin significantly reduced blood loss during coronary artery bypass surgery and was associated with a slight reduction in the amount of heparin administered. Activated coagulation time and activated partial thromboplastin time were prolonged by the addition of aprotinin. Activated coagulation time and activated partial thromboplastin time were poorly correlated with heparin assays. On the other hand, two other clotting tests designed to monitor heparin therapy, namely Titrarine (Stago, Asnière, France) and Heptest (Haemachem, St. Louis, MO), gave very good correlation with amidolytic heparin assays and can be used during extracorporeal circulation. Thrombin time showed a good correlation with amidolytic heparin assays after protamine administration and can be useful to detect residual heparin after heparin neutralization by protamine.

Antithrombins↗
PubMed1995

[Novel autograft method using positive selection of CD34 stem cells].

High dose chemotherapy with autologous blood stem cell rescue becomes widely used for patients with hematologic malignancies and solid tumors. Recently, it has been demonstrated that stem cells characterized by the CD34 antigenic marker could be positively selected using an anti CD34 monoclonal antibody and an avidin biotin immunoabsorption device. We report our experience of twelve selections and ten grafts. A CD34+ cells enrichment of 1.9 log (purity: 72%) and a CFU-GM cells concentration of 1.6 log have been obtained. In ten transplanted patients, the hematological recovery was similar to that obtained with non selected blood stem cells. The CD34+ cells purification allows mini graft infusion and purge of residual tumor cells implicated in relapse after autologous stem cells transplantation.

Adult↗
PubMed1994

Optimal blood stem cell mobilization using 10 micrograms/kg granulocyte colony-stimulating factor (G-CSF) alone for high-dose melphalan intensification in multiple myeloma: an intrapatient controlled study.

A recent randomized multicentric French study has shown that intensification with stem cell rescue improves the response rate and progression-free survival in multiple myeloma. Transplantation with primed peripheral blood stem cells (PBSC) displays a faster hematological recovery, especially for platelets, as compared with a bone marrow stem cell graft. In multiple myeloma, the optimal mobilization method for PBSC is unknown. The present study compares mobilization with cyclophosphamide 4 g/m2 + G-CSF 5 micrograms/kg versus G-CSF 5 micrograms/kg alone versus G-CSF 10 micrograms/kg alone in two cases of multiple myeloma, using an intrapatient controlled evaluation of the amount of CD34-positive cells obtained during each leukapheresis. In both cases, the highest CD34-positive cells yield was obtained with G-CSF at 10 micrograms/kg. Despite the low number of cases, this method, devoid of life-threatening toxicity, might be of greatest interest in multiple myeloma.

Antigens, CD↗
PubMed1994

Systemic release of interleukin-10 during orthotopic liver transplantation.

Experimental and clinical observations indicate that the liver allograft is less immunogenic than other organ transplants and can promote immune tolerance. Because interleukin-10 recently emerged as a macrophage and T-cell-derived cytokine with potent immunosuppressive properties, we studied its production in 28 patients undergoing orthotopic liver transplantation. Plasma levels of immunoreactive interleukin-10 dramatically increased within 2 hr after liver allograft reperfusion, with peak levels ranging between 214 and 4998 pg/ml (median = 677 pg/ml). This systemic release of interleukin-10 was transient because it returned to low levels by 48 hr (range = 26 to 51 pg/ml). The higher interleukin-10 levels measured in right atrial blood as compared with portal blood indicated that interleukin-10 was most likely synthesized within the liver graft. To get insight into the cellular origin of interleukin-10, we also measured serum levels of interleukin-4 and interferon-gamma, both produced by T cells, and interleukin-8, a cytokine secreted by macrophages, in eight patients. Interleukin-4 and interferon-gamma levels remained undetectable in most of the patients, whereas interleukin-8 levels paralleled those of interleukin-10. Portal endotoxemia was probably not involved in interleukin-10 production because endotoxin levels remained low (< 20 pg/ml) before and after liver allograft reperfusion. Interleukin-10 plasma levels did not correlate either with cold ischemia time or with the occurrence of rejection episodes. We conclude that orthotopic liver transplantation is associated with a massive release of interleukin-10 and interleukin-8, most likely produced by allograft macrophages.

Adult↗
PubMed1994

High-dose glucocorticosteroids increase the procoagulant effects of OKT3.

The use of OKT3 as prophylaxis in renal transplantation carries an increased risk of intragraft thrombosis, which is related to the systemic activation of the coagulation system that consistently occurs after the first dose of OKT3. As only a few patients develop thrombosis after OKT3 therapy, we searched for possible additional risk factor by comparing the demographic and clinical parameters of the 13 patients who developed thrombosis in our institution to those of 218 patients who did not. Multivariate analysis showed a relationship between the dose of methylprednisolone (mPDS) given before the first OKT3 injection and the risk of thrombosis: 6 out of 42 patients (14%) who received high (30 mg/kg) mPDS experienced a thrombotic event, as compared to 7 out of the 189 patients (3.7%) who received < or = 8 mg/kg of mPDS (P < 0.01). This led us to study the effects of mPDS on the procoagulant activity induced by OKT3 on peripheral blood mononuclear cells (PBMC) in vitro. The procoagulant activity of unstimulated PBMC (mean +/- SEM: 0.6 +/- 0.1 mU/ml) reached 3.0 +/- 0.7 mU/ml after OKT3 stimulation (P = 0.0062) and further increased to 7.4 +/- 2.0 mU/ml when PBMC were first preincubated overnight with mPDS before OKT3 stimulation (P = 0.018 as compared to OKT3 alone). This process involved the tissue factor/factor VII pathway, as shown by increased membrane expression of tissue factor on monocytes as well as by a marked reduction of the induced procoagulant activity when the clotting assay was performed with factor VII-deficient plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Interleukin-10 inhibits the induction of monocyte procoagulant activity by bacterial lipopolysaccharide.

Monocytes stimulated with bacterial lipopolysaccharide (LPS) generate a procoagulant activity (PCA) related to the induction of tissue factor (TF) expression at their surface. Since interleukin-10 (IL-10) was recently shown to inhibit LPS-induced cytokine production and is currently considered as a potential therapeutic agent in septic shock, we were interested to determine its effects on LPS-induced monocyte PCA. Peripheral blood mononuclear cells (PBMC) from healthy donors were incubated with 1 microgram/ml LPS in the presence of serial dilutions of recombinant human IL-10 and PCA was determined after 6 h in a one-stage clotting assay. IL-10 inhibited in a dose-dependent manner LPS-induced TF-dependent PCA: a significant effect was already observed with 30 pg/ml IL-10 while 64-97% inhibition was achieved with 120 pg/ml IL-10. In parallel flow cytometry experiments, IL-10 was shown to block LPS-induced TF expression at the surface of monocytes. In order to inhibit LPS-induced PCA, IL-10 had to be added to PBMC at least 6 h before LPS challenge. This inhibitory effect of IL-10 was already apparent at the TF mRNA level and was prevented by co-incubation with cycloheximide (20 micrograms/ml). These data suggest that IL-10 acts via the induction of protein(s) which might interfere with TF gene transcription or mRNA stability. We conclude that the protective effects of IL-10 in endotoxinemia might be related not only to cytokine synthesis blockade but also to inhibition of LPS-induced PCA.

Base Sequence↗
PubMed1992

Induction of thromboses within renal grafts by high-dose prophylactic OKT3.

Among 93 consecutive kidney-transplant patients who received prophylactic OKT3 10 mg/day for 2 weeks, 9 had intragraft thromboses within 2 weeks of transplantation. The thromboses were in graft artery in 1 patient and veins in 3. The other 5 had thromboses in glomerular capillaries and thrombotic microangiopathy similar to that of haemolytic-uraemic syndrome. All attempted treatments failed, and the 9 grafts had to be removed. The finding that plasma concentrations of prothrombin fragment 1 and 2 were higher 4 h after the first OKT3 dose in OKT3 recipients than in transplant patients who received other prophylaxis (mean 5.88 [SEM 0.76] vs 2.25 [0.59] nmol/l, p less than 0.01) confirms that OKT3 has procoagulant effects in vivo.

Humans↗
PubMed1992

Procoagulant effect of the OKT3 monoclonal antibody: involvement of tumor necrosis factor.

We recently observed that the prophylactic administration of high doses of OKT3 monoclonal antibody (MoAb) in cadaveric renal transplantation favors the development of thromboses of the grafts' main vessels and of thrombotic microangiopathies. These clinical observations led us to perform sequential determinations of plasma levels of prothrombin fragment 1 and 2 (F 1 + 2) and fibrin degradation products (FDP) after the first injection of 5 or 10 mg OKT3 given as prophylaxis in kidney transplant recipients. The values observed have been compared with those of kidney transplant recipients not treated with OKT3. F 1 + 2 levels peaked four hours after the first injection of 5 mg OKT3 (mean +/- SEM: 4.82 +/- 0.73 vs. 1.75 +/- 0.37 nmol/liter in controls, P < 0.01), indicating activation of the common pathway of the coagulation cascade. FDP levels were already above baseline values at four hours and continued to increase until 24 hours (mean +/- SEM at 24 hr, 4729 +/- 879 vs. 1038 +/- 320 ng/ml in controls, P < 0.05), indicating a fibrinolytic process. The magnitude and the time course of the changes in F 1 + 2 and FDP plasma levels were similar whether the patients received 5 or 10 mg dose of OKT3. The levels of von Willebrand factor (VWF) antigen, a molecule released by activated or damaged endothelial cells, were also significantly increased after injection of OKT3 (mean +/- SEM at 24 hr, 3.67 +/- 0.18 vs. 2.17 +/- 0.11 U/ml in controls, P < 0.05). The procoagulant effects of OKT3 were further investigated in vitro on human umbilical vein endothelial cells (HUVEC).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Hyperferritinemia in adult onset Still's disease and the hemophagocytic syndrome.

Increments in serum ferritin levels in adult onset Still's disease (AOSD) were reported to be higher than one could expect for a simple inflammatory state. When we analyzed the scores of 40 patients with various severe inflammatory diseases aside from AOSD, we recorded no serum ferritin values higher than 3,300 ng/ml (N less than 200 ng/ml). In 3 of 10 consecutive patients with AOSD, the ferritin levels were higher than 3,500. Among these 3 patients, one case had a ferritin value of 3,600 ng/ml and bone marrow aspirate showed a marked hyperplasia of mature appearing histiocytes, and the 2 other patients (serum ferritin levels of 65,000 ng/ml and 250,000 ng/ml) displayed the features of a hemophagocytic syndrome. In 2 patients with normal or mildly increased levels of ferritin, the bone marrow examination was normal. We suggest that very high serum ferritin levels encountered in AOSD reflect the presence of histiocytic hyperactivity that sometimes leads to a hemophagocytic syndrome.

Adult↗
PubMed1986

A simple indirect immunofluorescence micromethod for cell typing.

We describe a simple indirect immunofluorescence micromethod for cell typing. Cells are layered on 18-well immunofluorescence slides coated with high polymer poly-L-lysine. Expressed cell surface membrane markers are detected by indirect immunofluorescence using monoclonal antibodies and the cells are stained with Evans blue dye to permit easy morphological identification under fluorescence and light microscopy. We compared this method with a conventional method for lymphocyte typing in 16 blood samples and 10 bronchoalveolar lavage samples. The results of the two methods did not differ and correlated closely (r = 0.988 for blood samples; r = 0.995 for bronchoalveolar lavage samples). The principal advantages of this micromethod are: the small amounts of cells (10(4) cells) and reagents needed, the ease with which numerous antibodies can be tested and the convenience offered by fixation and staining of cell preparations for reading.

Animals↗
PubMed1986

Levels of antibodies to Plasmodium falciparum sporozoite surface antigens reflect malaria transmission rates and are persistent in the absence of reinfection.

Antibodies reacting with Plasmodium falciparum sporozoite surface antigens were measured by an immunofluorescence assay using wet preparations of sporozoites attached to poly-L-lysine-treated glass slides, a procedure which was found to be more specific than one using glutaraldehyde-treated and dried preparations. Subjects recovering from a first attack were found to be negative. In two African villages which differed in the level at which mosquitoes transmit the disease (1 and 100 infective bites per year and per individual), both the prevalence by age group and the levels of anti-sporozoite antibodies differed markedly, as follows. In the low-transmission area, these antibodies were not detected in subjects aged 2 to 10 years; thereafter, prevalence increased gradually with the age of the subject and reached 90% in subjects aged 50 to 80 years. In the high-transmission area, all of the subjects studied, including the younger ones, were positive. Anti-sporozoite antibody levels were independent of the levels of antibodies directed against blood stages. On average, the mean antibody titers were equal to 1/16 in the first village and 1/1,650 in the second one. These results suggest that stage-specific antibodies reflect the cumulative number of sporozoites inoculated in humans by mosquitoes and may therefore have useful epidemiological applications. In addition, the presence of stage-specific antibodies in the sera of African adults collected at different times after departure from the endemic area indicates that they may last for several years. During the course of this study, we observed a heterogeneity of immunofluorescence labeling in parasite populations prepared from mosquito salivary glands. This raises the question of possible qualitative or quantitative antigenic differences or both between one sporozoite and the other.

Adolescent↗
PubMed1986

[Micromethod of leukocyte typing using monoclonal antibodies and indirect immunofluorescence: cell adsorption on support slides treated with poly-L-lysine].

A micromethod of indirect immunofluorescence with monoclonal antibodies to study surface markers of leukocytes and precursors, is described. This method consists of attaching non specifically living cells on a slide, previously treated with a high molecular weight polymer (L-lysin). The advantage of this method consists of using only 1.10(4) cells by typage, and low amounts monoclonal antibodies (twenty to forty less). In addition, this common method can be used in most biology laboratories.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

[Retrospective analysis of results of treatment of 91 oral cavity cancers from 1982 to 1992].

PURPOSE: To analyse retrospectively the results of different treatment regimens of carcinomas of the floor of the mouth and tongue. MATERIALS AND METHODS: Between 1982 and 1992, 61 patients with carcinoma of the floor of the mouth and 30 with tongue cancer (25 stage I, nine stage II, 28 stage III, 29 stage IV) were treated in the radiotherapy department of Poitiers. Nine patients with stage I tumours were treated with 70 Gy low-dose rate brachytherapy only, without nodal dissection. Stages II and III were treated with combined surgery with neck dissection; and radiotherapy of stage II with nodal metastasis and for all stage III cases. Stage IV cases were treated either surgically if possible, or with combined chemotherapy and radiation. RESULTS: The five-year overall survival rate was 87.3% for stage I, 68.5% for stage II, 45.3% for stage III, and 0% for stage IV patients. Most relapses appeared in the first two years after treatment. Eight patients (32%) with stage I cancer developed nodal relapses, isolated in five cases. Complications of radiotherapy were acceptable. Four cases of osteonecrosis were observed after radiotherapy. All of these appeared simultaneously with a local relapse. CONCLUSION: These results are comparable with reports in the literature. The remarkable observation of our study is the high incidence of nodal recurrences after local treatment of stage I tumours. Therefore, local treatment is insufficient for early-stage tumours. The question of neck dissection for the early stage is discussed.

Adult↗