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L Bara

Publications and source records attributed to L Bara.

At least 37 records · Page 2Linked to original sources
PubMed1995

European Atherosclerosis Research Study: genotype at the fibrinogen locus (G-455-A beta-gene) is associated with differences in plasma fibrinogen levels in young men and women from different regions in Europe. Evidence for gender-genotype-environment interaction.

The European Atherosclerosis Research Study (EARS) compares genetic and environmental factors in the offspring of fathers with myocardial infarction before the age of 55 years (designated cases) and control subjects from five different regions of Europe. Genotype was determined for a G-A polymorphism 455 bp upstream from the start of transcription of the beta-fibrinogen gene. In 585 cases and 1106 control subjects, the relative frequency of the A allele was similar (0.223 and 0.217, respectively), with small and nonsignificant differences in frequency observed among the five regions. Because of evidence for an interaction between a number of factors and genotype in the determination of plasma fibrinogen levels (in particular among female cases who reported use of oral contraceptives), the data were analyzed without adjusting for covariates except for age and region, and analyses were carried out excluding women taking oral contraceptives (n = 297). In agreement with previous reports, in all regions the A allele was associated with elevated plasma fibrinogen levels, with the strongest and most consistent effects being seen in men. In nonsmokers, after adjusting for the effects of age and region, male cases and control subjects with genotype A/A had mean fibrinogen levels 0.49 and 0.33 g/L higher, respectively, than those with genotype G/G, whereas those with genotype G/A had intermediate levels (P < .01). In female nonsmokers there was a similar but smaller and nonsignificant effect (A/A levels higher than G/G by 0.12 and 0.07 g/L, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The 4G/5G genetic polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with differences in plasma PAI-1 activity but not with risk of myocardial infarction in the ECTIM study. Etude CasTemoins de I'nfarctus du Mycocarde.

We have investigated the interrelationships of plasma PAI-1 activity, the PAI-1 4G/5G polymorphism and risk of myocardial infarction (MI) in the ECTIM study, a case-control study of MI based in Belfast, Lille, Strasbourg and Toulouse. Mean PAI-1 levels in cases were similar across all centres but in controls, levels in the French centres were significantly higher. Only in Belfast were PAIl1 levels higher in cases (11.7 AU/ml) than controls (10.5 AU/ml). The PAI-1 4G allele frequency was similar in cases and controls (0.55 and 0.54). In all groups, 4G homozygotes had the highest mean plasma PAI-1 level (4G4G vs 5G5G; cases overall: 14.2 vs 12.1AU/ml; controls overall: 15.0 vs 12.6AU/ml), with the heterozygotes generally intermediate. The data from Belfast are consistent with the literature implicating PAI-1 level as an MI risk factor. In ECTIM, the PAI-1 4G/5G polymorphism is not a genetic risk factor for MI but is associated with PAI-1 activity. Thus homozygosity for the 4G allele may predispose to elevated PAI-1 and impaired fibrinolysis, perhaps requiring interaction with other genetic or environmental factors to influence MI risk.

Adult↗
PubMed1995

Changes in haemostatic variables induced by oral contraceptives containing 50 micrograms or 30 micrograms oestrogen: absence of dose-dependent effect on PAI-1 activity.

Several studies have suggested a dose-response relation between the oestrogen content of oral contraceptive (OC) and the risk of both venous thrombosis and arterial disease, when oestrogen doses were higher than 50 micrograms. However, there is no clear epidemiological evidence for a decrease in thrombotic risk with formulations containing less than 50 micrograms oestrogen. Therefore, we investigated haemostatic variables in users of OC containing either 30 micrograms (35 women) or 50 micrograms (29 women) ethinyl estradiol as compared with non users (64 women) matched for age and smoking status. Mean values of antithrombin activity were significantly lower in 30 micrograms or 50 micrograms oestrogen users than in non users (96% and 98% vs 105%, respectively, p < 0.001), but they were not significantly different between the two groups of OC users. There was a significant increase in mean values of factor VII antigen in women taking either 30 micrograms or 50 micrograms oestrogen as compared with non users (96% and 101% vs 85%, respectively, p < 0.005). Although the difference between both groups of OC users was not significant, a positive linear trend in factor VII levels was observed within the 0-50 micrograms oestrogen range (p < 0.001). Mean levels of fibrinogen were slightly higher in 30 micrograms or 50 micrograms oestrogen users than in non users (2.71, 2.66 g/l vs 2.55 g/l, respectively), but there was no significant difference between the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Plasma TFPI activity after intravenous injection of pentasaccharide (PS) and unfractionated heparin in rabbits.

Tissue Factor Pathway Inhibitor (TFPI), is known, to be released in plasma after injection of intravenous or subcutaneous injection of heparin or low molecular weight heparin (1,2). Addition of protamine or polybrene in plasma can neutralize anticoagulant effects of heparin in vitro but not completely ex vivo in patients treated with heparin (3). It was believed for many years that this post-heparin anticoagulant effect was due to another activity released by heparin. More recently it has been shown that post-heparin anticoagulant effect could be inhibited by anti-TFPI antibodies (4). Since we have shown in a previous work (5), that in healthy volunteers, pharmacokinetics of TFPI were more closely related to anti IIa activity than anti Xa activity we hypothesized that fragments with anti-IIa activity may be required for this release, possibly from vascular wall. In order to determine if a very low molecular weight glycosaminoglycan can release TFPI in plasma, in the present study, we compared plasma TFPI amidolytic activity after intravenous injection in rabbits of pentasaccharide (PS), a synthetic fragment of very low molecular weight and with a strong and exclusive anti Xa activity, and unfractionated heparin (UFH).

Animals↗
PubMed1994

Myocardial neutrophil sequestration and activation related to the reperfusion of human heart during coronary artery surgery.

OBJECTIVE: The aim was to determine if neutrophils are activated and sequestered as they pass through postischaemic human myocardium. METHODS: The occurrence of neutrophil activation during the reperfusion of the ischaemic myocardium was investigated in 16 selected patients undergoing coronary artery bypass surgery. Neutrophils were counted and elastase and lactoferrin released into the plasma were measured simultaneously in myocardial venous blood and in peripheral venous blood, before aortic cross clamping (T0), and two (T1), 10 (T2), and 20 (T3) min after unclamping. RESULTS: At T0, no statistically significant difference was noted between peripheral and myocardial blood with respect to the three variables studied. Reperfusion was associated with a significantly lower neutrophil count in myocardial blood compared to peripheral blood (p < 0.001), suggesting that neutrophils were trapped within the myocardium during reperfusion. In addition, levels of elastase (T1, T2, and T3), and lactoferrin (T1) were significantly higher in myocardial blood as compared to peripheral blood (p < 0.001), suggesting that activated neutrophils released their granular content into the plasma milieu. CONCLUSION: We provide evidence consistent with local neutrophil activation during myocardial reperfusion in patients undergoing coronary artery bypass surgery, in addition to the well described systemic activation related to cardiopulmonary bypass.

Adult↗
PubMed1994

An animal model for the evaluation of graft thrombosis in the acute phase on carbon-lined PTFE prosthesis.

Forty-five carbon-lined (CL) and 45 standard (ST) 4 mm internal diameter polytetra-fluoroethylene (PTFE) grafts were implanted as aortic interposition in 90 rabbits. A pilot study of 20 animals: 10 CL and 10 ST grafts were used to develop microsurgical techniques, then 60 grafts were placed in 60 New Zealand rabbits with lower morbidity. The two hours graft patency (Doppler and angiographic studies) showed better patency rate in CL group (93% versus 80%). In 10 animals, platelet accumulation was investigated in vivo using gammacamera imaging after injection of autologous platelets labeled with Indium111. In vitro, radioactivity counting of the explanted midgraft sections at 2 hours revealed 6 times greater activity in ST grafts (6.60 +/- 1.98 x 10(3) platelets/mm2 versus 0.82 +/- 0.25 x 10(3) platelets/mm2; p < 0.05). Light microscopy found platelet and fibrin deposition (PFD) in nearly all ST grafts whereas PFD were found in only 13% of the CL grafts corresponding to those thrombosed (chi 2: 61.117, p < 0.001). Carbon-lining decreases platelet accumulation on PTFE grafts in the acute phase of a new experimental model.

Angiography↗
PubMed1994

Expression of a paternal history of premature myocardial infarction on fibrinogen, factor VIIC and PAI-1 in European offspring--the EARS study. European Atherosclerosis Research Study Group.

To assess the role of genetic and environmental factors in the predisposition to atherosclerosis, 682 students whose father had suffered a myocardial infarction before the age of 55 ("cases") and 1312 controls matched for age and sex, were recruited from 14 Universities in Europe. Fibrinogen, factor VIIc and PAI-1 were compared between cases and controls across European regions. Fibrinogen and factor VIIc were positively correlated with BMI, smoking and contraception. PAI-1 was positively and independently correlated with BMI and waist-to-hip ratio, and negatively with contraception. Factor VIIc and PAI-1 were correlated with cholesterol and triglycerides, and fibrinogen was weakly correlated with LDL-cholesterol. After adjustment for covariates and lipids, fibrinogen level was significantly higher in male cases than in controls (2.38 vs 2.29, p < 0.01). No such difference was found in females (2.59 vs 2.57 - NS). There was no significant case/control difference for factor VIIc and PAI-1. These results support the hypothesis that fibrinogen is a transmissible risk factor of coronary artery disease in males. No such evidence was provided for factor VIIc and PAI-1.

Adolescent↗
PubMed1993

Haemostatic variables and menopausal status: influence of hormone replacement therapy.

Large cohort studies have shown that postmenopausal estrogen use was associated with a reduction in the risk of coronary heart disease. This putative beneficial effect of hormone replacement therapy (HRT) may be partly mediated through changes in clotting factors and fibrinolytic system. We have measured haemostatic variables in 293 consecutive healthy women aged 45-54 years who attended a health check-up centre in Paris (IPC). Premenopausal women taking hormonal therapy were excluded (n = 34). Most women using HRT were given 17-beta estradiol in combination with progestin. Mean levels (m +/- sd) of plasma fibrinogen, factor VII coagulant activity and plasminogen activator inhibitor (PAI) were significantly higher in postmenopausal women not taking HRT (n = 99) than in premenopausal women (n = 139) within the same decade (319 +/- 52 mg/dl vs 304 +/- 60 mg/dl, 107 +/- 17% vs 96 +/- 16%, 9.73 +/- 5.71 U/ml vs 7.61 +/- 4.36 U/ml respectively). Allowance for main cardiovascular risk factors made no substantial differences to the results, although the effect of the menopause on fibrinogen was no longer significant. HRT (n = 21) significantly reversed the menopause-related changes in factor VII (94 +/- 15%), even after adjustment for confounding factors. The same trend in both fibrinogen (294 +/- 46 mg/dl) and PAI (8.22 +/- 5.51 U/ml) was observed. Similar results were found in women using oral or percutaneous estrogen. Our findings suggest that 17-beta estradiol in combination with progestins may protect against an increased thrombotic tendency in postmenopausal women. Randomized clinical trials are urgently needed for a better understanding of HRT effect on atherothrombotic process.

Coronary Disease↗
PubMed1993

Comparative effects of enoxaparin and unfractionated heparin in healthy volunteers on prothrombin consumption in whole blood during coagulation, and release of tissue factor pathway inhibitor.

In a randomized crossover study twelve healthy male volunteers (23.5 +/- of 4.8 years, 73.0 +/- 6.4 kg, 180.8 +/- 5.7 cm) received one subcutaneous injection of either enoxaparin (EN) at 40 mg or 1 mg kg-1, or unfractionated heparin (UH) at 5,000 IU at one week intervals. Area under curves (AUC) of Anti-Xa and Anti-IIa activities correlated with EN dose. The relative effectiveness of EN versus UH 5,000 U as assessed by AUC ratio (EN/UH) was 7 and 15 for Anti-Xa activity, 1.3 and 3.1 for Anti-IIa activity after sc injection of EN 40 mg (4,000 Anti-Xa IU and 1,200 Anti-IIa U) and 1 mg kg-1 (7,300 +/- 640 Anti-Xa IU and 2,190 +/- 290 Anti-IIa IU) respectively. In volunteers receiving EN, a dose dependent inhibition of thrombin generation rate in platelet depleted plasma (PDP), measured with a new and simple chromogenic thrombin generation assay, was observed when compared with baseline values. Similarly, intrinsic prothrombin activation in whole blood, evidenced by measuring residual factor II in serum 2 hours after clotting (prothrombin consumption test: PC), was inhibited in a dose dependent manner. In UH treated volunteers, although the inhibition of thrombin generation rate in PDP was similar to that observed with EN 40 mg, prothrombin consumption in whole blood was not significantly modified. Tissue factor pathway inhibitor (TFPI) activity release was increased similarly for UH and EN 40 (1.4 fold increase above baseline values) and 1.9 fold for the higher dose of EN. The discrepancy between prothrombin consumption in whole blood and inhibition of thrombin generation rate in PDP in the UH and not in the EN group strongly suggests that UH and not EN is influenced by the presence of a platelet component. This could be formed during thrombin induced platelet activation. Platelet factor 4 is a possible candidate. Another hypothesis involves the role of TFPI-UH complex anticoagulant activity which might be inhibited more during whole blood coagulation than the TFPI-EN complex.

Adult↗
PubMed1993

Factor Xa inhibition: correlation between the plasma levels of anti-Xa activity and occurrence of thrombosis and haemorrhage.

A multicentre, double-blind, randomised trial was conducted to compare the efficacy of a low-molecular-weight (LMW) heparin, Logiparin, with that of an unfractionated (UF) heparin in the prophylactic treatment of thrombosis in patients undergoing general surgery. A total of 1,290 patients were randomised to receive a single daily dose of Logiparin (2,500 IU: 431 patients; 3,500 IU: 430 patients) or UF heparin (2 x 5,000 IU: 429 patients). The incidence of the main end point, deep venous thrombosis, was found to be significantly different between the groups (p = 0.03), whereas the incidence of severe haemorrhage was not (p = 0.05). The plasma anti-Xa activity was found to be correlated with body weight, but correlated only very weakly with antithrombotic activity (p = 0.045) after adjustment in a stepwise multivariate analysis, and did not significantly correlate with the incidence of haemorrhage. Logiparin at 3,500 IU and UF heparin showed similar efficacy. Although a correlation between plasma anti-Xa activity and body weight was observed, there is not sufficient evidence to recommend the adjustment of the Logiparin dose on patient's weight for prophylaxis in general surgery patients.

Body Weight↗
PubMed1993

Genetic variation at the beta-fibrinogen locus in relation to plasma fibrinogen concentrations and risk of myocardial infarction. The ECTIM Study.

Increased plasma fibrinogen concentration is a major cardiovascular risk factor. Conflicting results on genetic variations in plasma fibrinogen levels have been reported. Furthermore, whether fibrinogen genotype is associated with the risk of ischemic heart disease has not been studied so far. An HaeIII restriction fragment length polymorphism of the beta-fibrinogen gene was used in a case-control study to investigate the genetic variation at this locus in relation to plasma fibrinogen concentrations and the risk of myocardial infarction (MI). Five hundred thirty-three male patients aged 27-66 years and 648 control subjects were recruited from four World Health Organization MONICA centers in Northern Ireland and in France. The absence of the HaeIII cutting site (H2 allele) was associated with a significant rise in fibrinogen concentrations in both patients and control subjects. The effect of the HaeIII polymorphism on plasma fibrinogen levels did not significantly differ between centers. Fibrinogen levels were higher in smokers than in nonsmokers. The difference between the two groups was larger in subjects with the genotype H2H2 than in those with either genotype H1H1 or H1H2, regardless of the case-control status. However, there was no significant interaction between smoking status and genotype in their effects on variance in fibrinogen levels, whereas fibrinogen levels. HaeIII genotype accounted for approximately 1% of the total variance in fibrinogen levels, whereas smoking and age together explained 7% and 5% in control subjects and patients, respectively. The frequency of the H2 allele was 0.21 in control subjects and 0.19 in patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A comparative study of recombinant hirudin and standard heparin in the Wessler model.

The in vitro anticoagulant activity of recombinant desulphated hirudin (HBW 023) and its antithrombotic activity in a rabbit venous stasis model were assessed in comparison to unfractionated heparin (UH). The specific activity of r-hirudin in rabbit plasma is similar to that of unfractionated heparin on a weight basis when using the whole blood clotting time or APTT, while it was five times more potent according to the thrombin clotting time (TCT). Forty-eight (6x8) anaesthetized New Zealand male rabbits were randomized to receive HBW 023 (12.5, 25, 50, 100, 200, 400 micrograms.kg-1), standard heparin (90 micrograms.kg-1) or placebo. Five minutes after administration of the drug, the experimental thrombosis was induced by an injection of glass activated overnight human serum into the marginal vein of the ear and ligation of the jugular vein (Wessler model). The jugular vein was removed after 10 min stasis and examined by a researcher unaware of the treatment administered. In the Wessler stasis model the fresh thrombus weight and a score as well as the circulating level of r-hirudin using a chromogenic substrate assay were used to determine the inhibitory effect of the drug. Highly significant inverse correlations were found between fresh thrombus weight and the injected doses as well as r-hirudin plasma levels. The ID50 which was the dose of the drug that induced a complete inhibition of thrombosis in 50% of the dose group tests was about 200 micrograms.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction.

Factors involved in the pathogenesis of atherosclerosis, thrombosis and vasoconstriction contribute to the development of coronary heart disease. In a study comparing patients after myocardial infarction with controls, we have explored a possible association between coronary heart disease and a variation found in the gene encoding angiotensin-converting enzyme (ACE). The polymorphism ACE/ID is strongly associated with the level of circulating enzyme. This enzyme plays a key role in the production of angiotensin II and in the catabolism of bradykinin, two peptides involved in the modulation of vascular tone and in the proliferation of smooth muscle cells. Here we report that the DD genotype, which is associated with higher levels of circulating ACE than the ID and II genotypes, is significantly more frequent in patients with myocardial infarction (n = 610) than in controls (n = 733) (P = 0.007), especially among subjects with low body-mass index and low plasma levels of ApoB (P < 0.0001). The ACE/ID polymorphism seems to be a potent risk factor of coronary heart disease in subjects formerly considered to be at low risk according to common criteria.

Adult↗
PubMed1992

Correlation between anti-Xa and occurrence of thrombosis and haemorrhage in post-surgical patients treated with either Logiparin (LMWH) or unfractionated heparin. Post-surgery Logiparin Study Group.

A total of 1290 patients (Pts) undergoing general surgery were enrolled in a randomized, multicentre double-blind study in order to investigate the efficacy and safety of two different doses of a low molecular weight heparin (LMWH) (Logiparin) for the prevention of deep vein thrombosis. Patients were randomized to either 5,000 IU unfractionated heparin twice daily, 2,500 anti-Xa or 3,500 anti-Xa units of Logiparin once daily. Each treatment was given subcutaneously two hours before surgery and continued for seven to ten days. All coagulation tests were performed blindly in a core laboratory. Blood samples were collected before surgery and then 3 hours after injection on Day 3 and 5 after surgery. Anti-Xa amidolytic activities were significantly higher in the two LMW Heparin groups than in the unfractionated heparin group (mean peak levels +/- s.e.m. on Day 3: 0.097 +/- 0.004; 0.152 +/- 0.004 and 0.034 +/- 0.003 IU respectively). As expected a significant correlation was observed between anti-Xa activity and the dose of LMW Heparin injected. The correlation coefficient was higher when the doses were expressed in anti-Xa units/kg body weight. However, the body weight accounts for only 16% of the interindividual variability of anti-Xa activity. Therefore, there is no clear evidence to suggest that weight-adjusted doses should be recommended when this LMW Heparin is used as prophylactic treatment in general surgery. A weak negative correlation was found between anti-Xa activity and thrombosis as demonstrated by a positive radiolabelled fibrinogen uptake test and confirmed by positive phlebography. No significant correlation was demonstrated between anti-Xa activity and the occurrence of postoperative bleeding.

Body Weight↗