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Biomedical subjects

P Capel

Publications and source records attributed to P Capel.

At least 37 records · Page 2Linked to original sources
PubMed1996

CD40 engagement induces monocyte procoagulant activity through an interleukin-10 resistant pathway.

Interactions between membrane-bound molecules were previously shown to be involved in the induction of tissue factor-dependent monocyte procoagulant activity (PCA) by activated T cells. To investigate the potential role of the CD40/CD40 ligand (CD40L) pathway in this process, we first determined the effects of blocking anti-CD40 or anti-CD40L monoclonal antibodies (mAb) on the development of monocyte PCA during mixed lymphocyte reaction (MLR) between allogeneic peripheral blood mononuclear cells (PBMC). The strong inhibitory effect exerted by both mAb (mean percentages of inhibition: 88 and 91% for anti-CD40 and anti-CD40L mAb, respectively) indicates that CD40/CD40L interactions are required for the induction of PCA in MLR. These data led us to measure monocyte PCA after incubation of PBMC or purified monocytes with a stimulating anti-CD40 mAb (BL-C4) or with 3T6 fibroblasts transfected with the gene encoding CD40L. In both systems, we found that CD40 engagement strongly induced monocyte PCA which was related to tissue factor expression as shown by flow cytometric analysis. Finally, we observed that recombinant interleukin (IL)-10, which inhibits lipopolysaccharide-induced PCA, did not significantly influence CD40-dependent PCA. We conclude that CD40 engagement on monocytes induces tissue factor-dependent PCA through an IL-10-resistant pathway. These findings have implications for the control of coagulation events triggered by interactions between T cells and monocytes.

Antibodies, Monoclonal↗
PubMed1996

Low response to high-dose intravenous immunoglobulin in the treatment of acquired factor VIII inhibitor.

Prednisone is the classic first-line therapy to suppress an acquired factor VIII inhibitor and may achieve complete remission in about 30% of patients. More recently, promising results have been reported with high-dose intravenous immunoglobulin (IVIg). However, after an extensive review of the literature, we found only three complete remissions (12%) among the 26 assessable patients treated by IVIg. These data are in agreement with the low response to IVIg that we experienced in our series of patients. This study suggests that steroids should still be preferred to IVIg, an expansive therapy, to suppress an acquired factor VIII inhibitor.

Adult↗
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↗
PubMed1996

Variations in fibrinolytic activity of human whole saliva.

The physiological variations of fibrinolytic activity (FA) in saliva were investigated in a population of 149 healthy volunteers including 12 pregnant women. An increase in FA could be observed with increasing age. Marked variations were observed during daytime with a peak value early in the morning. Higher FA values were observed in males as compared with females in the 20-39 yr age group. A clear decrease in FA was observed during pregnancy. A significant correlation existed between FA and suspended epithelial cell concentration, which seemed responsible for most of the physiological FA variations. It was concluded that age, sex, pregnancy, and the time of the day are important for salivary FA and should be taken into account in any study on salivary FA related to physiological or pathological processes.

Adult↗
PubMed1996

[Cardiovascular diseases: toward an optimal use of clinical biological laboratories].

Cardiovascular diseases are a frequent cause of morbidity and mortality in our country. The early detection of risk factors by laboratory tests and the subsequent preventive treatment may have a substantial beneficial effect on public health. However, since these tests are performed on large populations, they must be chosen with caution, in order to optimise their cost/ effectiveness ratio. Savings obtained by the judicious use of the clinical lab could allow, already in 1996, the reimbursement of some new informative tests, like the plasma homocysteine and the LDL-cholesterol, and later, of the lipoprotein (a), all tests which are presently at the charge of the patient.

Blood Chemical Analysis↗
PubMed1996

Clinical evidence for an engraftment syndrome associated with early and steep neutrophil recovery after autologous blood stem cell transplantation.

Seventy autologous peripheral blood stem cell transplants (APBSCT) performed in 61 cancer patients were retrospectively analyzed. Patients were heterogenous with regard to malignancy, conditioning regimens and use of growth factors after transplantation. Six patients developed a non-infectious fever, fluid retention and pulmonary interstitial infiltrates during the early phase of neutrophil recovery. Diarrhea was observed in four of these patients and cutaneous rash in three. The clinical condition improved spontaneously in one patient, and within 48 h after steroid therapy in four. One patient died from multiple organ failure. Age, sex (all patients were female; P = 0.07), and time to platelet recovery did not distinguish the six courses complicated by the hypothetical engraftment syndrome (ES) from the other 64 courses taken as controls. However, neutrophil recovery > 0.5 x 10(9)/l occurred earlier (P = 0.01), and the neutrophil count increment during the early phase of recovery was steeper in ES patients (P = 0.003). ES was also associated with infusion of a high number of CD34+ progenitors (P = 0.03) and conditioning with busulfan (P = 0.03). Although all ES patients received G-CSF after transplantation, an association of ES with G-CSF use could not be demonstrated, possibly because of the small number of courses not supported by G-CSF. However, in one patient, ES did not recur after a second transplant unsupported by growth factors. Our study supports the idea of an engraftment syndrome associated with an early and steep neutrophil recovery after APBSCT.

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

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↗
PubMed1995

PCNA immunopositivity index as a substitute to 3H-thymidine pulse-labeling index (TLI) in methanol-fixed human lymphocytes.

PHA-stimulated human lymphocytes or myelogenous leukemia cells (strain K-562) were pulse labeled with 3H-thymidine and submitted to various fixation-permeabilization procedures. They were then immunostained with the 19A2, 19F4 or PC10 monoclonal antibody against the proliferating cell nuclear antigen (PCNA). The preparations were finally scored for the proportion of unlabeled, double-labeled and single PCNA or 3H-thymidine-labeled nuclei. Unstimulated lymphocytes were immunonegative in all the conditions tested, as also were stimulated lymphocytes checked with an isotype of the primary antibody. A specificity (Sp) and a sensitivity (Se) score was calculated to evaluate the recognition by PCNA staining of the S-phase cells, as defined by the 3H-labeling. The data show that in most instances the three antibodies recognized the 3H-labeled cells with high sensitivity, ie with few false negative, but with low specificity, ie with PCNA positivity extending to variable proportions of non-S-phase cells. By contrast, methanol fixation followed by a brief treatment with the detergent Triton X-100 and immunostaining with either 19F4 or PC10 (but not with 19A2) combined a high sensitivity and specificity scores of the recognition of the 3H-thymidine-labeled cells: PC10 gave a more intense and, hence, more readable reaction. PHA-stimulated lymphocytes that had been preserved at -20 degrees C as cytocentrifuged smears failed to show any immunopositivity for PCNA if not submitted to further fixation prior to the immunocytochemical assay. When methanol-Triton was used for this step, only PC10 gave positive immunoreaction, yet with a lower specificity score (Sp = 76%) than in cells submitted to this fixation-permeabilization procedure without prior cryopreservation (Sp = 91.7%). The PCNA index was measured in cryopreserved, methanol-fixed smears of lymphocytes from patients with various hematological diseases and was compared to the Ki-67 index established independently on a serial sample. A good correlation was found between the two indices (r = 0.79; P < 0.0001) with the PCNA index generally lower than or close to the Ki-67 index. This warrants a note of caution about the use of total (ie stable and labile) PCNA immunostaining to measure the growth fraction (GF), classically defined as the proportion of proliferating cells in a population. However, in the absence of an absolute reference marker for G0 cells, there is no reason to assume that the PCNA index would necessarily be a worse estimate of GF than the Ki-67 index.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoradiography↗
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

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

Successful alpha-2b-interferon therapy for chronic neutrophilic leukemia.

The authors report two patients with characteristic features of chronic neutrophilic leukemia (CNL) treated with alpha-2b-interferon (IFN) (Schering-Plough). At initiation of therapy, both patients had progressive disease and presented with large tumors. A rapid reduction of the tumor mass and a long-term stabilisation of the myeloproliferative disorder was obtained (therapy duration 16 and 26 months, respectively, and presently ongoing). In one patient, the dose of IFN could be significantly reduced during maintenance without relapse. Neither presented infectious or hemorrhagic complications under therapy. Alpha-2b-interferon is active and safe in CNL, even pretreated and progressive. It can also correct the neutrophil and natural killer functional defects frequently observed in CNL.

Aged↗
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↗