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Biomedical subjects

M Samama

Publications and source records attributed to M Samama.

At least 73 records · Page 4Linked to original sources
PubMed1990

Does increased platelet aggregation have a prognostic value in the deterioration of background diabetic retinopathy? The Damad Study Group.

Many case-control studies have suggested that increased platelet aggregation (PA) could be involved in the pathogenesis of diabetic microangiopathy. However, longitudinal data are needed to support this hypothesis. We consider here such an approach in the placebo group (93 diabetic patients) of a controlled clinical trial on the effect of PA inhibitors in the treatment of diabetic retinopathy (Damad program). We have measured spontaneous PA and PA induced by ADP, collagen and arachidonic acid before treatment and yearly during a 3-year period. The assessment of retinopathy was based on the changes in the number of microaneurysms present in the macular field as seen on fluorescein angiograms during follow-up. PA was estimated by maximal decrease in optical density. The lowest ADP concentration still able to induce irreversible aggregation was also determined. No significant correlations between any baseline PA measurements and end point criterion were found (all correlation coefficients lower than 0.20). No significant changes in mean PA were observed during follow-up. Within-subject variation of PA was markedly large accounting for 61% to 98% of the total variance of various measurements. Allowances for the main characteristics of diabetes made no substantial difference to the results. These negative findings can be partly attributed to the lack of reliability of PA tests. In our study, we conclude that PA tests are not useful measures for the prediction of evolution of background diabetic retinopathy.

Adenosine Diphosphate↗
PubMed1990

Aequorin-detected calcium changes in stimulated thrombasthenic platelets. Aggregation-dependent calcium movement in response to ADP.

Calcium changes in normal and thrombasthenic platelets were recorded using the PICA-apparatus. Aequorin was loaded in the presence of DMSO, EGTA and PGE1. Platelets of three patients with type I thrombasthenia stimulated with A-23, 187, thrombin, PMA in the presence 1 mM Ca++ and 1 mM Mg++ were able to normally raise their calcium concentrations. The maximal values could be found below the normal range with collagen, ADP and PAF-acether. Calcium mobilization from internal stores in response to thrombin was normal. There were two calcium peaks in normal platelets stimulated with ADP. The second one was suppressed by omitting fibrinogen, stirring, or by adding aspirin, and was absent in thrombasthenic platelets. Thus the GP IIb-IIIa complex is not a prerequisite for calcium fluxes but is involved, when weak agonists such ADP are used, through an aggregation-dependent reinforcement of platelet activation.

Adenosine Diphosphate↗
PubMed1990

In vitro effect on Heptest of low molecular weight heparin fractions and preparations with various anti-IIa and anti-Xa activities.

The Heptest heparin assay has recently been introduced, and evaluated for the laboratory monitoring of patients receiving low molecular weight heparins (LMWH). The aim of the present study was to elucidate the relative role on the Heptest assay of the anti-factors Xa and IIa activities present in the three types of compounds that possess: 1. exclusively anti-Xa activity (LF1: LMWH fractions with MW ranging from 1,200 to 4,200 D.); 2. both anti-Xa and anti-IIa activities (LF2 with MW from 4,800 to 12,000 D.); 3. exclusive anti-IIa activity (Hirudin and Dermatan Sulfate). All compounds studied demonstrated dose-dependent activities in both amidolytic and clotting assays. The LF2 in contrast to the LF1, additionally enhanced the clotting times of Heptest. This enhancement was shown to be due to the anti-Factor IIa activity of the agents. Heptest does not exclusively reflect Anti-Xa activity since it is influenced by agents containing exclusive anti-IIa activity like Hirudin and Dermatan Sulfate. At low concentrations of LF2, Heptest measures predominantly the anti-factor Xa activity while at higher concentrations it is influenced by the combined activity of anti-factor Xa and anti-factor IIa. However, Heptest sensitivity to anti-factor IIa is significantly lower than for anti-Xa activity.

Chondroitin↗
PubMed1990

Factor VII activation and menopausal status.

The incidence of coronary heart disease (CHD) is higher in postmenopausal or oophorectomised women than in premenopausal women of the same age. The difference cannot be explicable in terms of conventional CHD risk factors. Since factor VII may be relevant to the pathogenesis of CHD, we have investigated the menopause-related changes in factor VII activation in 228 healthy women aged 45-54 years. A standard factor VII clotting assay (FVIIc) and a factor VII antigen assay (FVIIag) were carried out on the same plasma samples. Both FVIIc and FVIIag levels were significantly higher in postmenopausal than in premenopausal women. Despite the strong correlation between the two assays (r = 0.80), the FVIIc/FVIIag ratio was positively and significantly associated with the menopause, suggesting that activated factor VII form might in part account for the high FVIIc levels in postmenopausal women. With respect to the type of menopause, the highest levels of both FVIIc and FVIIc/FVIIag ratio were found in women having undergone bilateral oophorectomy. These results suggest that raised factor VII coagulant activity may contribute to an increased risk of CHD in postmenopausal women.

Antigens↗
PubMed1990

Degradation of fibrinogen by tissue plasminogen activator. Consequences for fibrin polymerization.

In patients treated with tissue plasminogen activator (t-PA), there was a marked increase in concentration of fibrinopeptide A (fpA). The purpose of this study was to analyse the activation of coagulation in plasma treated in vitro by pharmacological doses of t-PA. From our results, it appears that fpA release due to direct interaction of fibrinogen with t-PA, in the absence of plasminogen, is very low and not observed with pharmacological doses of t-PA. In contrast in the presence of plasminogen, the release of fpA is much higher and induces fibrin formation concomitantly to fibrinogen degradation.

Biopolymers↗
PubMed1990

Ultraviolet irradiation of platelet concentrates: feasibility in transfusion practice.

Ultraviolet (UV)-B irradiation abolishes lymphocyte functions (the ability to respond and to stimulate) in mixed lymphocyte culture (MLC). This effect may have practical application in the prevention or reduction of transfusion-induced alloimmunization against HLA class I antigens. To study this, platelet concentrates (PCs) were obtained with a cell separator, suspended in autologous plasma in a final volume of 400 mL, and transferred into a large (22 X 30 cm) cell culture bag. This plastic showed a good transmittance of UV-B rays at 310 nm (54%). PCs were placed between two quartz plates (surface of irradiation = 25 X 37 cm), and the two sides were irradiated simultaneously. Energy delivered to the surface of the plastic bag was automatically monitored. The ability to respond (in MLC and to phytohemagglutinin) and to stimulate allogeneic lymphocytes was completely abolished with energy of 0.75 J per cm2 (irradiation time less than 3 min). The temperature increase during irradiation was negligible. Platelet aggregation (collagen, adrenalin, ADP, arachidonic acid, ristocetin) was not impaired if UV-B energy was below 3 J per cm2. Recovery and survival of autologous 111In-labeled platelets were studied in four volunteers; no differences were found between UV-B-treated (1.5 J/cm2) platelets and untreated platelets. These results show that a large-scale clinical trial using UV-B-irradiated PCs to prevent HLA alloimmunization is feasible.

Blood Platelets↗
PubMed1990

Pharmacokinetics of low molecular weight heparins.

When measured in terms of biological activities (using only markers of molecules with affinity for antithrombin III), the pharmacokinetics of low molecular weight heparins are clearly different from those of unfractionated heparin after intravenous and subcutaneous injections. The plasmatic anti-Factor Xa activity half-life, whatever the injected dose of the different low molecular weight heparins, is about two to four times longer than for unfractionated heparin while anti-Factor IIa plasmatic half-life is only slightly longer for enoxaparin than for unfractionated heparin. Preferential endothelial cell binding of high molecular weight heparin chains that possess greater anti-Factor IIa activity may partly explain these differences. When measured in terms of radioactive markers of molecules with either high or low affinity for antithrombin III, in native form or degraded after endocytosis by endothelial cells, using 99 m technetium labelled heparins in human volunteers, the pharmacokinetics in blood, urine and organs are similar whatever the heparin used (enoxaparin or unfractionated heparin). The radioactive half-life was longer than that of the biological activity. These results suggest that enoxaparin binds less than unfractionated heparin to proteins other than antithrombin III and that enoxaparin is partly eliminated in urine as active metabolites.

Factor Xa Inhibitors↗
PubMed1990

Prevention of thromboembolic disease in general surgery with enoxaparin (Clexane).

Different low molecular weight heparins have been compared with unfractionated heparin for the prevention of venous thrombosis in general surgery in about 20 controlled therapeutic trials since 1984. The Multicentre Genox Study* included 892 patients in three consecutive randomized studies with a daily dose of 60, 40 and 20 mg of enoxaparin, respectively, the first injection given 2 h prior to surgery, as compared to subcutaneous unfractionated heparin 5000 IU tds. All included patients had at least one additional risk factor for thrombosis, in addition to surgical risk and to age over 40 years. This trial was the first to compare low molecular weight heparins to controls receiving three daily injections of unfractionated heparin instead of two, and to use three different daily doses of a low molecular weight heparin. The trials were conducted in abdominal, gynaecologic, urologic and thoracic surgery. About 30% of patients had malignancy. Percentages of positive 125I-fibrinogen uptake test (isotopic thrombosis) were comparable: 2.9, 2.8 and 3.8% with enoxaparin and 3.8%, 2.7% and 7.6% with unfractionated heparin, and were not significantly different. There was a significant decrease in haematocrit and haemoglobin only in those patients receiving 60 mg of enoxaparin. The conclusion of this study was that a daily dose of 20 or 40 mg of enoxaparin (approximately 2000 and 4000 anti-Factor Xa IU) was safe and not statistically different from unfractionated heparin. No biological control, except platelet counts before treatment and then twice a week, is required in prophylaxis.

Aged↗
PubMed1990

[Increase of erythrocyte aggregation in retinal vein occlusion].

Erythrocyte aggregation is one of the principal determinants of blood viscosity at low shear rates (low flow). Anatomical and hemodynamical characteristics make retinal venous circulation particularly dependent on hemorheological factors. Erythrocyte aggregation and other laboratory parameters (haematocrit, fibrinogen, plasma proteins, clotting) were measured in 85 patients presenting with retinal vein occlusion and 64 controls matched for age, sex and vascular risk factors (hypertension, diabetes, smoking). Statistical analysis of the results demonstrated a significant difference between the retinal vein occlusion group an the control group for erythrocyte aggregation (p less than 0.001 for the aggregation index at 10 sec and for the threshold of dissociation). The fibrinogen level, haematocrit and plasma proteins (albumin, IgA, IgG, IgM, total proteins, 2-macroglobulin) were similar in the two groups. No statistically significant difference for erythrocyte aggregation was observed between occlusions of the venous branch and occlusions of the central retinal vein or between ischaemic and non-ischaemic forms. These results suggest that raised erythrocyte aggregation mainly explains the increase in blood viscosity previously demonstrated, and could play a role in the constitution of retinal vein occlusion.

Acute Disease↗
PubMed1990

[Biological monitoring of treatment with antivitamin K. Value of INR and definition of new therapeutic ranges. A study of 73 patients].

The prothrombin time test (PT) is the most common method used for monitoring oral anticoagulant therapy. As a consequence of the variability in responsiveness of different thromboplastins, PT results obtained from patients on oral anticoagulant therapy may not be interchangeable between laboratories and as consequence could produce potential problems for anticoagulant control. The conversion of PT in INR (International Normalized Ratio) has been introduced recently to standardise the PT used for anticoagulant control. 127 determinations of prothrombin time and INR with 2 different thromboplastin reagents (Thromboplastin C Dade and Owren reagent) have been performed in 73 patients. This study confirm the usefulness of the INR (INR discrepancy in 10% of the cases) despite the imperfections concerning the choice of the control plasma and the need of a precise measurement of the ISI, International Sensitivity index. In parallel, changes in therapeutic ranges for anticoagulant therapy occurred, based on results of the international literature: less intense anticoagulant treatment (INR 2-3) is effective against recurrent venous thromboembolism with reduced bleeding. Different therapeutic ranges must be recommended for oral anticoagulant therapy according to the indication of the treatment.

Administration, Oral↗
PubMed1990

[Anistreplase. Pharmacology and biological data].

Anistreplase is a second generation thrombolytic agent, an equimolecular streptokinase lys-plasminogen complex the active site of which is temporarily blocked by a p-anisoyle group. Acylation enables the drug to be administered as a bolus intravenous injection over 2 to 5 minutes, and it protects anistreplase against circulating inhibitors, hence a plasma elimination half-life of 90 minutes. Deacylation is slow and progressive (deacylation half-life: 105 minutes), and it begins as soon as the product is injected. It reduces the hypotensive effect of streptokinase, permits a prolonged action in the thrombus and limits the risk of reocclusion. Using lys-plasminogen increases the affinity of the drug for fibrin and potentiates its accumulation and retention in the thrombus. In vitro studies have shown that the affinity of anistreplase for fibrin is similar to that of t-PA. In doses used for myocardial infarction, anistreplase induces a pronounced fibrinogenolysis. The effectiveness of the drug has been demonstrated on numerous animal models and subsequently by clinical trials.

Anistreplase↗
PubMed1989

Effect of standard heparin and a low molecular weight heparin on thrombolytic and fibrinolytic activity of single-chain urokinase plasminogen activator in vitro.

The effect of unfractioned heparin (UH) and low molecular weight heparin (LMWH) (Kabi 2165 - Fragmin) on in vitro scu-PA thrombolytic and fibrinogenolytic activity was investigated. Thrombolytic activity was evaluated by following lysis of radiolabeled plasma clot immersed in plasma in presence of scu-PA alone or with either form of heparin. A 200 IU/ml scu-PA concentration produced clot lysis within 7 hr. UH or LMWH led to a slightly faster clot lysis which was statistically significant only at the 2nd and 3rd hour. No significant difference could be evidenced between UH and LMWH effect. During clot lysis, plasmin, generated within the clot led to a gradual transformation of scu-PA to tcu-PA, specially after a 4-hr incubation. Appearance of tcu-PA activity in the plasma surrounding the clot was significantly inhibited by either form of heparin. This finding contrasts with results observed in purified systems and suggests the presence of heparin-dependent plasma factor(s) inhibiting tcu-PA formation or its activity. Possible candidates might be anti-thrombin III and PAI-3. No fibrinogen breakdown was observed when plasma was incubated for 7 hr at 37 degrees C in presence of scu-PA alone (200 IU/ml) or with either form of heparin. However, in presence of a plasma clot, an important fibrinogen breakdown was observed during clot lysis reflecting the action of plasmin and/or tcu-PA generated within the clot, in the surrounding plasma. Fibrinogenolysis was less pronounced in the presence of both heparin preparations possibly as a consequence of the reduction in the tcu-PA level. These results underline the importance of plasma factors in the interaction of heparin with plasminogen activators such as scu-PA.

Fibrinogen↗
PubMed1989

Calcium rise in human platelets elicited by anti-CD9 and -CD41 murine monoclonal antibodies.

Three murine monoclonal antibodies (anti-CD9: ALB6, anti-CD41: VI-PL3 and PL2-49/GPIIb - final concentration: 7.5 micrograms/mL) are shown to elicit after a lag time aggregation of washed platelets and a calcium signal (as detected by light emitted by loaded aequorin), which is only partially inhibited by aspirin. By comparison the rise induced by thrombin is greater and almost instantaneous. In the presence of EGTA a calcium mobilization from internal stores can be detected with thrombin and with ALB6, but neither with PL2-49 nor with VI-PL3, whereas platelets still change their shape and release ATP. It is tempting to speculate that although all the antibodies induce a calcium change, they activate platelets by different pathways: calcium may be not primarily involved in the activation induced by the anti-CD41 antibodies.

Adenosine Triphosphate↗