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Biomedical subjects

F Fabris

Publications and source records attributed to F Fabris.

At least 145 records · Page 8Linked to original sources

Lack of antiplatelet activity of the new coumarin derivative 8-monochloro-3-beta-diethylaminoethyl-4-methyl-7-ethoxy- carboxylmethoxycoumarin under in vivo conditions in man.

Antiplatelet properties of AD 6 (8-monochloro-3-beta-diethylaminoethyl-4-methyl-7-ethoxy-carboxyl- methoxycoumarin) have been studied in vitro and in vivo. The drug showed a marked inhibitory effect on platelet aggregation, beta-thromboglobulin (beta TG) release and thromboxane B2 (TxB2) production in vitro. However, such effects were seen only in the presence of high concentrations of the drug (10(-3) and 10(-4) mol/l) and completely disappeared at lower concentrations. No effect was seen in vivo following oral administration of 300 mg of the drug in a small group of volunteers. It can be concluded that in vitro properties of the drug cannot be surmised without due caution to indicate its potential clinical use.

Adenosine Diphosphate↗

Disappearance of human platelet factor 4 (PF4) in rabbits: does an immediate component exist?

Twelve male New Zealand rabbits were injected with 21 micrograms/kg of human platelet factor 4 antigen (PF4). The decay of the protein followed a monoexponential curve for the first 5 mins, with a half-life (t 1/2) of 1.94 mins and a calculated concentration at 0 time (CO) of 79.4 ng/ml. Five rabbits were pre-treated with heparin (2.500 I.U. i.v.) and 3 mins later were injected with the same amount of PF4. PF4 decay followed a monoexponential curve with a t 1/2 of 25.3 mins, and with CO of 380.8 ng/ml. This value is not greatly different from the one calculated assuming an immediate and uniform distribution in plasma (482.7 ng/ml for a plasma volume of 43.5 ml/kg). The 12 rabbits injected with PF4 were divided in 3 groups, in which heparin was given at 10', 30' or 60' after PF4, respectively. After heparin the peak levels of PF4 were 139.9 ng/ml, 65.3 ng/ml and 52.7 ng/ml, respectively. The following monoexponential PF4 decay had t 1/2 of 20.7, 25.6 and 26.0 mins, respectively. In a separate group of 4 animals, we studied heparin decay after an intravenous bolus of 2.500 I.U. Heparin decay could not be described by a monoexponential equation and was different from the decay of PF4 injected after heparin. On the basis of the present data we suggest the presence of an immediate component of PF4 decay, most likely due to uptake by the tissues. Heparin pretreatment may avoid this uptake process.

Animals↗

The evaluation of factor VIII antigen by means of a simple slide test.

Factor VIII von Willebrand may be detected by a Ristocetin-dependent platelet agglutination reaction. The authors have measured plasma levels of Factor VIII-related Ristocetin cofactor (VIIIR:RCoF) using formalin-fixed platelets tested by an aggregometric method or by a new, commercially available glass slide test. Plasmas were obtained from patients with von Willebrand's disease and Cushing's syndrome, and from normal controls. Von Willebrand factor (vWf) levels varied between 0-500% of the normal. A good correlation (r = 0.95) was found comparing the results obtained by the two methods over the entire range. If all patients were considered, a satisfactory correlation was obtained between VIIIR:RCoF and VIII-related antigen (VIIIR:Ag), both by the aggregometric method (r = 0.79) and by the glass slide method (r = 0.88). On the contrary, if values below 25% of the normal are taken into account, only a mild correlation was found between VIIIR: RCoF (aggregometric method) and VIIIR:Ag and no correlation between VIIIR:RCoF (glass slide method) and VIIIR:Ag. No correlation, regardless of the method used, was found between VIIIR:RCoF and VIIIR:Ag for values above 120%.

Antigens↗

Effect of heparin and aspirin on platelet and clotting activation during leukapheresis.

Beta-thromboglobulin (beta TG), serotonin (5HT) and fibrinopeptide A (FPA) were assessed in twenty-two normal donors before, during, and at the end of leukapheresis. Seven procedures were carried out adding heparin to the circuit, and seven adding acetyl salicylic acid (ASA). The remaining eight procedures were carried out using only citrate and served as controls. Plasma beta TG increased both during and after the apheresis, together with a significant decrease of the intra-platelet content. Platelet 5HT did not show significant changes whereas FPA increased significantly. Using heparin, we obtained a complete prevention of FPA cleavage during the entire procedure, while beta TG increased at the middle of the procedure. No significant effects were observed using ASA both on beta TG and FPA levels. These features clearly indicate the activation of platelets and the thrombin generation in the apheresis circuit. Nevertheless, the activation of the clotting system seems to be predominant, as supported by the improved effect of heparin on beta TG and FPA amounts.

Adult↗

PF 4 versus beta TG as evidence for platelet activation in myeloproliferative disorders.

19 patients with MPD have been studied. As described in normals, an age-related increase in beta thromboglobulin (beta TG) release is observed. Such release, however, is greater in patients with myeloproliferative disorders (MPD). MPD seem therefore to cause platelet activation, allowing an earlier and more evident manifestation of physiologic ageing phenomena. PF 4 levels are near zero both in controls and patients, regardless of platelet number. This suggests that increased levels of PF 4 represent only a laboratory artifact, caused by platelet activation in vitro. Mean ability in producing thromboxane B2 (TxB2) is increased, but is perfectly normal in patients with normal platelet count and decreased in 3 thrombocythaemic patients, who seem to present an increased thrombotic risk. TxB2 is reduced almost to zero by the administration of aspirin plus dipyridamole; contrarily, all other parameters were unaffected, either by such drugs or by AD 6, a new coumarin derivative with antiplatelet properties.

Adult↗

The effect of different doses of 32P in the treatment of primary thrombocytosis.

We report on a follow up in 23 patients with primary thrombocytosis treated with two different doses of 32phosphorus phosphate (32P). Ten patients with essential thrombocytosis (ET) received 2 mCi and 13 patients with polycythemia vera (PV) received the standard dose of 0.1 mCi/kg b.w. The patients were listed as having a complete response (CR), partial response (PR) or no response (NR) considering platelet count at 3 and 12 months after 32P injection. The results indicate the existence of a clear correlation of the rate of remission with the 32P injected dose. PV patients show, in fact, a percentage of complete remission higher than ET patients. However, the use of higher doses induces more early and long-term complications.

Adult↗

[Significance of hemorheological parameters within the framework of chronic brain disease].

Blood filtration and viscosity were investigated in 32 patients with severe mental deterioration classified on the basis of standard criteria. The group included 17 patients with 'vascular' and 15 with 'cellular' pathogenesis. The results of the study were compared with the data from a large series of 'normal' subjects. Reduced erythrocyte filtration was observed in 70.5% of the patients with vascular pathogenesis and in only 6.6% of those with degenerative conditions. The data on blood viscosity showed less connection between pathological conditions and hemorheological alterations. It is suggested that hemorheological alterations might contribute to the pathogenesis of certain clinical forms of chronic cerebropathy. It is therefore proposed that hemorheological tests should be included among the diagnostic procedures applied to such patients and might also be used in order to establish the appropriate treatment.

Aged↗

Effects of ticlopidine on blood fibrinogen and blood viscosity in peripheral atherosclerotic disease.

Ten patients with peripheral atherosclerotic disease(PAD) treated with 750 mg/d of 5-(2-chlorophenylmethyl)-4,5,6,7-tetrahydrothieno (3,5-c-pyridine) hydrochloride (ticlopidine, Tiklid) were studied for three months. As control was studied a similar group of patients treated with a traditional vasodilator (nicotinate). The aim of our study was to evaluate the effect of ticlopidine both on the clinical evolution of the disease and on rheologic, coagulative and platelet parameters. A progressive increase of maximal walking distance was noted during the three months of therapy with ticlopidine and limited to the first 30 days of treatment with nicotinate. The fibrinogen levels resulted significantly lowered during 90 days of treatment with ticlopidine, while that was not evident in the nicotinate group. There was also a slight improvement of blood viscosity in the ticlopidine group (not evident in the nicotinate group), but it was not statistically significant. No further modifications of investigated data were found in the two groups of patients. The clinical benefit of ticlopidine in PAD without adverse reactions can be confirmed at least at the dosage of 750 mg/d instead of the usual dose of 500 mg/d. A direct or indirect action of ticlopidine on plasma fibrinogen is suggested. This observation may supply new clues for the understanding of the mechanism of action of this drug.

Aged↗

Clearance and in vivo release by heparin of human platelet factor 4 (PF4) in the rabbit.

13 male New Zealand rabbits were injected with two different doses (25 micrograms/Kg and 100 micrograms/Kg) of human platelet factor 4 antigen (PF4). The disappearance of the protein was extremely fast with an half-life for the fast component of 1.07 +/- 0.16 and 1.76 +/- 0.11 min respectively. The half-life for the slow component, detectable only with the highest dosage, was 18.8 min. The administration of 2500 I.U. of heparin 30 min after PF4 administration induced a partial release of the injected protein and its clearance from plasma was slow, with half-life of 23.3 +/- 5.9 min and 30.9 +/- 2.19 min respectively.

Animals↗

Clinical significance of beta-thromboglobulin in patients with high platelet count.

The aim of the study was to investigate the relevance of beta-thromboglobulin (beta tg) measurement in patients with thrombocytosis. We have, therefore, studied the level of plasma and platelet beta tg in 74 patients with high platelet count in addition to the evaluation of platelet aggregation and platelet serotonin (5-HT) content. The determinations of platelet serotonin content and aggregation are confirmed to be useful in the differentiation between primary and secondary forms of thrombocytosis. The mean plasma level of beta tg in patients with myeloproliferative disease was significantly raised, but the amount observed in subjects with secondary thrombocytosis is increased too. Considering the amount of beta tg in relation to whole blood platelet count (beta tg ratio), no difference was observed between all patients and controls. The beta tg ratio allowed the identification of a group of patients with an increased ratio and a decreased beta tg platelet content who showed the highest occurrence of thrombosis (66%).

Adult↗

A microplate enzyme-linked immunospecific assay (ELISA) detecting unbound anti-platelet antibodies.

A microplate immune-enzymatic method was developed for detecting serum antiplatelet antibodies. The method involves the use of antigen-coated platelets and alkaline phosphatase-labeled antihuman immunoglobulin. Linear correlation was obtained between the titer of platelet antibodies and substrate conversion. Twenty-four patients with immune thrombocytopenia and 40 normal controls were studied. Eighteen patients and one control were positive. Therefore, sensitivity and specificity were 75% and 97% respectively. ELISA also was found to be more sensitive than the indirect antiglobulin consumption assay (ACA) and appears to be a practical and easy method for routine evaluation of antiplatelet antibodies.

Binding Sites, Antibody↗

Manometric study on anal sphyncteres and intestinal MTT before and after extensive surgery on patients affected by cervical carcinoma. Clinical experiences.

The Authors report the preliminary results of a study performed on patients submitted to radical hysterectomy according to Wertheim-Meigs for cervical-carcinoma, in order to evidence possible changes of the intestinal functionality, by means of a manometric investigation of the anal sphyncteres and measurement of the intestinal transit times. The manometric survey showed that no essential parameter was uniformly altered whereas the transit time measurement proved in some cases the slowing-down of the intestinal progression at the level of the ascending and transverse colon, and a normal transit in the descending colon as well as in the rectum in all examined cases.

Adult↗

Antithrombin III (AT III) Padua2: a "new" congenital abnormality with defective heparin co-factor activities but no thrombotic disease.

A "new" antithrombin III (AT III) abnormality is described in five members of the same family. None of the affected members showed thrombotic manifestations and no consanguinity was present in the family. The main laboratory features were: normal routine clotting tests, slightly decreased AT III activities in all assays carried out in the presence of heparin. In the absence of heparin, antithrombin III activities were instead within normal limitis. Progressive AT III activity and AT III antigen were also normal. Crossed immunoelectrophoresis in the absence of heparin showed a normal pattern both in plasma and serum. In the presence of heparin, the propositi's plasma showed a major, less anodal, abnormal peak and a smaller normal peak. Three peaks were present in the propositi's serum as compared with the two normal ones. This AT III abnormality is different from AT III Padua previously described by us and we propose the toponym of Antithrombin Padua-2 to define this condition.

Adult↗