Search PubMed⌕ Search

Biomedical subjects

M A Lazzari

Publications and source records attributed to M A Lazzari.

At least 37 records · Page 2Linked to original sources
PubMed1997

Low-intensity oral anticoagulation plus low-dose aspirin versus high-intensity oral anticoagulation alone: a randomized trial in patients with mechanical prosthetic heart valves.

BACKGROUND: Mechanical heart valve replacement requires lifelong anticoagulant treatment. Aspirin has proved useful in further reducing thromboembolic events when added to oral anticoagulants. However, increased (gastrointestinal) bleeding was observed at the doses previously tested for this combination in heart valve prostheses. METHODS: We performed a prospective randomized trial to compare the combination of low-intensity oral anticoagulants (international normalized ratio 2.5 to 3.5) plus aspirin (100 mg/day) (arm A) versus high-intensity oral anticoagulants alone (arm B) (international normalized ratio 3.5 to 4.5). Arm A included 258 patients and arm B 245 patients. The two groups were comparable for all baseline characteristics. RESULTS: The outcomes of the study were embolism, valve thrombosis, and major hemorrhage. The median follow-up was 23 months. The two treatments offered similar antithrombotic protection. The incidence of embolic episodes was 1.32 per 100 patient-years (95% confidence interval 0.53 to 2.7) for arm A and 1.48 per 100 patient-years (95% confidence interval 0.59 to 3.03) for arm B. Major hemorrhage occurred in 1.13 per 100 patient-years (95% confidence interval 0.41 to 2.45) for arm A and 2.33 per 100 patient-years (95% confidence interval 1.17 to 4.14) for arm B. Gastrointestinal bleeding was not increased by this combined reduced dose of aspirin and coumarin.

Anticoagulants↗
PubMed1997

Enhanced response to chemotactic activation of polymorphonuclear leukocytes from patients with heart valve replacement.

Artificial surfaces activate blood components. Since anticoagulant and antiplatelet therapy fail to abolish thromboembolic complications in patients with mechanical heart valve replacement (MHVR), other mechanisms might contribute to switch on a thrombotic event. We therefore investigated the reactivity to chemotactic activation of PMN from patients with MHVR. PMN responses were analyzed in 3 groups: 130 patients with MHVR and oral anticoagulant therapy, with or without aspirin, 57 patients on a comparable antithrombotic regimen, but without MHVR and 50 healthy subjects. In vitro studies showed that the release of cathepsin G and elastase from fMLP-stimulated PMN was significantly higher in the MHVR group, the leukocyte content of alpha 1-antitrypsin (an inhibitor of both enzymes) being similar in all three groups. CD11b expression after stimulation with fMLP was also significantly higher on PMN from MHVR patients than from control patients or healthy volunteers, while PMN CD11b basal expression was similar in all three groups. This increased PMN response in vitro in the absence of an obvious activation in vivo, may reflect a modified reactivity of circulating PMN passing through the artificial valves. Increased reactivity to local stimuli might allow PMN to participate in thrombus formation, despite conventional antithrombotic therapy.

Anticoagulants↗
PubMed1997

Anti-factor VIII inhibitors and lupus anticoagulants in haemophilia A patients.

In a study of 170 haemophilia A patients, 43 were found to have an inhibitory effect; seven had anti-factor VIII inhibitors (a-fVIII)(A), 18 had lupus anticoagulants (LAs) with a strong (B: 12) or weak (C: 6) time-dependent effect and 18 had no time-dependent LAs (D). The a-fVIII showed a neutralizing effect only against factor VIII and negative diluted Russell viper venom time (dRVVT). The LAs were diagnosed by dRVVT; the Staclot LA agreed with the dRVVT. During the study, three patients changed from an a-fVIII to an LA pattern; they also modified their clinical response. Our prevalence of a-fVIII was low (4%) and we found 21% of LA, with a high (50%) prevalence of time-dependent inhibition. This pattern raises the possibility of the coexistence of LA and a-fVIII, stressing the need to develop specific tests to identify a-fVIII and LA.

Algorithms↗
PubMed1997

Requirement of a plasma fraction for the loss of large von Willebrand factor multimers induced by high wall shear rate.

The perfusion of serum, citrated whole blood and citrated plasma, through a simple tube system resulted in a significant loss of large von Willebrand factor (vWf) multimers, without decrease in antigen levels. Maximum loss of large multimers was observed at a shear rate of 15,000 s-1 for 15 min. Heparin, aprotinin, soybean trypsin inhibitor, phenylmethylsulphonylfluoride, N-ethylmaleimide, leupeptin or calpain inhibitor peptide could not prevent the loss of large vWf multimers in citrated plasma. The addition of EDTA calcium salt partially prevented it, and it was totally prevented by EDTA without calcium. Perfusion of purified vWf did not induce the loss of large multimers, but this did happen after the addition of either whole serum or a plasma fraction. The activity of this plasma fraction disappeared at pH < 6.8. Besides, we have found that the binding to subendothelium of purified vWf diluted in dialyzed serum was lower at pH 7.2 than at pH 6.0. Chromatographic studies demonstrated that the loss of large vWf multimers, induced by high shear rates, involves a plasma substance(s) of molecular weight larger than 200 kD; calpain and granulocyte or cysteine proteases do not seem to be this plasma substance(s).

In Vitro Techniques↗
PubMed1994

Platelet aggregation inhibition by mononuclear leukocytes.

In this study we have investigated the effect of human mononuclear leukocytes (ML) on platelet aggregation. The results obtained demonstrated that coincubation of platelets with nonstimulated ML decreased platelet aggregation induced by collagen or thrombin in a concentration-dependent manner. The inhibitory effect increased with the incubation period of the cells, reaching a plateau at 5 minutes. T and non-T enriched ML suspensions exerted an inhibitory effect similar to the total population of ML. Supernatants from ML or mixed cell suspensions also diminished platelet aggregation. 6-keto PGF1 alpha concentration in the supernatants was less than 10 pg/ml. Hemoglobin, L-arginine and cytochrome C did not modify the antiaggregating activity of ML, whereas superoxide dismutase potentiated the inhibition of aggregation mediated by ML. The inhibitory effect was not modified by monoclonal antibody (MoAb) against the lymphocyte function-associated antigen 1, alpha subunit (LFA-1 alpha) or by a MoAb directed against P-selectin. Our results demonstrated that ML inhibited platelet aggregation, at least partially, by the release of a soluble factor(s) distinct of prostacyclin or nitric oxide. Surface adhesion molecules seem also not to be involved.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Behavior of diluted activated partial thromboplastin time in pregnant women with a lupus anticoagulant.

The present study was developed to verify whether a reduction in phospholipid concentration could increase the activated partial thromboplastin time (APTT) sensitivity to detect lupus anticoagulant (LA) during pregnancy. The authors studied 38 pregnant women (10 normal subjects and 28 patients with associated clinical complications) and 40 nonpregnant control subjects. Tests to detect LA, including APTT, platelet neutralization procedure (standard APTT), the kaolin clotting time, the diluted Russell viper venom test neutralized by lysed platelets, and factor assays, were performed. Positive results were found in 5 of 28 pregnant women with associated clinical complications. The APTT, using three different phospholipid concentrations (standard and more diluted cephalin), was performed on plasma samples and on its 1:1 mixture with normal plasma. The behavior of standard and diluted APTT was similar in negative LA pregnant women and nonpregnant control subjects. The mean values showed nonsignificant differences. Four of five pregnant women with positive LA findings had a prolonged APTT, which was not corrected by the addition of normal plasma using standard conditions. When diluted phospholipids were used, only one of them had a prolonged APTT that was corrected by the addition of normal plasma. Therefore, the highest sensitivity (80%) and specificity (100%) of the APTT to detect LA in pregnant women were obtained using the standard conditions.

Female↗
PubMed1992

A simple enzyme-immunoassay test for von Willebrand factor binding in human arterial subendothelium.

In order to determine the binding of vWF, subendothelium from everted human umbilical arteries was perfused with dialysed serum containing different concentrations of purified vWF using an annular perfusion chamber at a wall shear rate of 1100 sec-1 for 30 min. After perfusion, control (not perfused) and perfused vessel segments were washed and incubated with a diluted rabbit antibody against human vWF. Then the nonbound anti-vWF from both samples were used to determine indirectly vWF by EIA. Although in our experiments normal vWF serum concentrations were not enough to exert vWF binding, a substantial binding could be attained with vWF levels around 2.5 U/ml. To estimate the pre-existing subendothelial vWF amount, three different experiments were developed: a) diluted IgG from a nonimmunized rabbit, b) a diluted rabbit antibody to human vWF, c) PBS-BSA. After washing, vessel segments were incubated with rabbit antibody to human vWF. After incubation, the nonbound anti-vWF was used to determine indirectly vWF by EIA. The results obtained showed that the amount of pre-existing vWF was approximately 1.1x10(-3) U vWF/cm2 subendothelium.

Endothelium, Vascular↗
PubMed1991

Visualization of platelet glycoproteins Ib and IIIa by immunoenzymatic stain using avidin-biotin peroxidase complex.

A method is described here for the identification and quantitation of antigens by monoclonal antibodies. This method is based upon 1) separation (crossed-immunoelectrophoresis) and immunoprecipitation (rocket immunoelectrophoresis and crossed immunoelectrophoresis) of glycoproteins Ib and IIIa with a polyspecific antiserum; 2) binding of the non precipitating monoclonal antibody to glycoproteins precipitated by the rabbit antibody; 3) visualization of the monoclonal antibody with secondary biotinylated antibody and after addition of avidin biotin peroxidase complex, the peroxidase activity is detected by 4-Cl-1-naphtol. By this technique, the agarose gel plate could be stained directly and this allowed us to eliminate electrophoretic transblotting and radioactive compounds.

Animals↗
PubMed1991

Interferon-gamma enhances PAF-acether production by stimulated human polymorphonuclear leucocytes.

Human polymorphonuclear leucocytes (PMN) stimulated with either immune complexes (IC), phorbol myristate acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (FMLP) generate platelet-activating factor (PAF-acether). The present study demonstrates that treatment of PMN with recombinant human interferon-gamma (IFN-gamma) significantly enhanced the production of PAF-acether by stimulated cells, in a concentration-dependent mode. On the contrary, alpha and beta IFN were completely unable to increase PAF-acether synthesis by stimulated PMN. The significance of these results is discussed.

Antigen-Antibody Complex↗
PubMed1990

Inhibition of human platelet activation by polymorphonuclear leukocytes.

1. The effect of unstimulated human polymorphonuclear leukocytes (PMNs) on platelet activation was examined. 2. Human platelet aggregation and adenosine 5'-triphosphate (ATP) release induced by collagen (1-2 micrograms ml-1); thrombin (0.01-0.02 u ml-1) or arachidonic acid (AA) (0.1-0.2 mM) were markedly inhibited when conducted in the presence of unstimulated PMNs. 3. Platelet inhibition induced by PMNs was dependent on the number of PMNs and on the incubation time of the mixed cell suspension. 4. Platelet inhibition was not reversed in time when PMNs were depleted from the mixed-cell suspension. 5. PMN-mediated platelet-inhibition was not mediated by AA metabolites, oxygen reactive intermediates, nitric oxide or proteases. 6. The factor(s) accounting for the platelet inhibition mediated by PMNs are not yet characterized.

Adenosine Triphosphate↗
PubMed1989

Hormonal regulation on bioactive aortic substance (BAS) production.

Rat's vessel wall releases a protein named BAS (Bioactive Aortic Substance) whose antiaggregating effect on platelets and inotropy vascular properties have been already described. In this work we have investigated the effects of pregnancy, gonadectomy and gonadectomy with hormonal treatment on the BAS production from rat aortic rings. BAS production in pregnancy and ovariectomized rats was markedly decreased compared to normal rats. Return to normal values was obtained after estradiol treatment in ovariectomized rats. Castration resulted in an increased of BAS production which was suppressed by testosterone treatment.

Animals↗