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Biomedical subjects

F Fabris

Publications and source records attributed to F Fabris.

At least 19 recordsLinked to original sources

Labeling of platelet surface glycoproteins with biotin derivatives.

We describe a non-radioactive method for the labeling of platelet surface proteins, consisting of platelet protein biotinylation by means of N-hydroxysuccinimido-biotin (NHS-B) and biotin-hydrazide (H-B); NHS-B labels proteins amino residues while H-B binds to periodate-modified sialoglycoproteins. Washed platelets were biotinylated and protein bands were detected after SDS-electrophoresis and western-blot using avidin-peroxidase and luminol as substrate to enhance the signal which was then detected by X-ray film. Biotin-labeled platelet proteins were also immunoprecipitated with monoclonal antibodies against glycoproteins Ib and the IIb-IIIa complex. The use of periodate induced biotinylation is the method of choice for labeling platelet surface glycoproteins while NHS-B also labels internal proteins. The sensitivity of this new procedure is similar to that obtained with radiolabeling techniques; biotinylation does not interfere with the antigenic properties of Ib and IIb-IIIa glycoproteins.

Antibodies, Monoclonal

A four year clinical and echographic follow-up of asymptomatic carotid plaque.

Eighty-five patients with asymptomatic carotid plaque--a diagnosis revealed by B-mode high-resolution echotomography--were followed up for four years; the echoplaque changes were compared with the clinical history. Eight patients died (2 from stroke, 4 from myocardial infarction, and 2 from lung tumor) and were excluded from the follow-up. Three patients underwent carotid thromboendarterectomy (TEA) (1 bilateral), and these 4 carotids were not considered in the total series. At the first echo Doppler evaluation of 150 carotids, plaques were observed in 112; 38 vessels were free of lesions. Of the 150 carotids, 8 revealed a new plaques. In regard to the echogenic pattern, 95 of the 112 plaques (84.8%) remained unchanged, 16 (14.3%) progressed, and regression of a small homogeneous plaque was observed in 1 patient (0.9%). An increase of the degree of vascular stenosis, was observed in 23 of the 150 carotids (15.3%). Cerebral ischemic symptoms occurred in 5 patients. In 1 patient who suffered from stroke, a new, soft, dyshomogeneous plaque in the carotid of the side of the lesion was observed. In 3 patients (2 with strokes, 1 with transient ischemic attack) the occlusion of a previous severe stenosis was observed. The fifth patient had a stroke on the side of an unchanged, ulcerated hemodynamic lesion. A valid criterion for identifying a risky plaque should be the joint evaluation of the echostructural characteristics and the degree of stenosis.

Arteriosclerosis

[Lipid parameters and cardiovascular risks in elderly patients hospitalized for ischemic cardiopathy. A case-control study].

In order to evaluate whether and to what extent elevated blood lipid concentrations and clinical expressions of coronary heart disease (CHD) are associated in the elderly, we studied the risk of CHD (myocardial infarction and angina pectoris) in a population of elderly hospitalized patients (210 subjects, 126 men and 84 women, average age 76 +/- 6 years) exposed to risk factors. 210 patients, free from current and previous cardiovascular diseases, age and sex matched, were recruited as the control group. Advanced senile decline, severe hepatic or renal failure and malignancies were considered exclusion criteria for both groups. The following dichotomic variables (familial history of CHD, cigarette smoking, clinical history of arterial hypertension or diabetes mellitus, hypercholesterolemia, hypertriglyceridemia) and continuous variables (total, LDL and HDL cholesterol, triglycerides, total/HDL cholesterol ratio, body mass index (BMI), years of exposure to risk factors) were considered. Using a stepwise multiple logistic regression forward method, the following variables resulted significantly associated with the risk of CHD: total/HDL cholesterol ratio (OR 1,89), BMI (OR 1,04), period of hypertension (OR 1,04) and cigarette smoke exposure (OR 1,007). We conclude that in the elderly the total/HDL cholesterol ratio can be a more predictive and reliable index of coronary risk than blood total cholesterol concentration.

Aged

[Prevalence and risk factors of carotid and femoral atherosclerosis in a sample of the city of Turin].

Presence and severity of carotid and femoral atherosclerosis, in relation to the principal cardiovascular risk factors, have been non invasively evaluated using echodoppler in a sample of 457 subjects (average age 55.4 +/- 18.7 years) of the metropolitan area of Turin. Data of prevalence have been standardized for age and gender in order to obtain an estimate of prevalence representative of the city. In both districts, prevalence of lesions, echo structural characteristics of the plaques and related degree of stenosis have been considered. Results indicate a high prevalence of carotid and femoral atherosclerosis (38.5% and 39.4% respectively), and, particularly, of concomitant involvement of both districts (30%). Prevalence of the lesions and degree of stenosis rise with advancing age; nevertheless stenosis > 75% were not found among the oldest patients. Bifurcations were the most frequent site of lesion and the "hard" echo structure was the most commonly represented, especially in subjects over 45 years. After multiple logistic regression model both carotid and femoral atherosclerosis were strongly and independently associated with age, male sex, smoke of cigarette and plasma cholesterol concentration.

Adolescent

Indobufen versus dipyridamole plus aspirin in the treatment of patients with peripheral atherosclerotic disease.

Twenty-seven patients with peripheral atherosclerotic disease were randomized into two therapy regimens consisting of indobufen (Indo) (400 mg/day) and dipyridamole (Dip) (225 mg/day) plus acetylsalicylic acid (ASA) (1 g/day), respectively. Maximal walking distance (MWD) and ankle-arm systolic pressure ratios were measured before and after three and six months of therapy; bleeding time, beta-thromboglobulin (beta-TG), platelet factor 4 (PF4) and serum thromboxane B2 (TXB2) were also assessed. The two treatment groups showed a significant and progressive increase in pain-free walking distance at both three and six months of therapy, but patients taking indobufen showed a greater improvement. On the contrary, the pressure doppler ratio at rest was statistically improved only in the ASA plus Dip group. Basal beta-TG and PF4 levels were normal and no changes occurred during the study in either group, while in all patients bleeding times showed a significant increase above basal values and serum TBX2 decreased.

Aged

[The relationships between the lipoprotein profile and rheological-coagulation parameters in patients with hyperlipoproteinemia type II].

The aim of the study was to evaluate the direct influence of lipid parameters (total and HDL-cholesterol, triglycerides and total lipids) on the rheologic-coagulative pattern. We studied blood rheological properties--blood (BV), plasmatic (PV), and seric (SV) viscosity, whole blood (WBF) and red cell (RCF) filterability--and some coagulative factors--fibrinogen (Fib), levels of clotting factor VII (fVIIc) and VIII (fVIIIc) activity--in 156 men aged 40-54 years; 87 patients had type II hyperlipoproteinemia (46 type IIa and 41 type IIb) and 69 were normolipemic controls. Smokers, patients with arterial hypertension, diabetes mellitus or cardiovascular clinical manifestations were excluded. Type IIb hyperlipoproteinemic patients had increased blood viscosity (shear rate 225 sec-1, p. less than 0.01), which was positively correlated with triglycerides and fibrinogen concentration. Levels of fibrinogen, fVIIc and fVIIIc activity did not differ significantly in hyperlipemic patients and controls, although fVIIc activity and fibrinogen were both positively related with lipid parameters. These data suggest that, in absence of other major risk factors, the alterations of the rheologic-coagulative pattern are mainly dependent on the severity of the lipid disorder.

Adult

Effect of human recombinant erythropoietin on bleeding time, platelet number and function in children with end-stage renal disease maintained by haemodialysis.

We studied platelet number and function in nine anaemic children with end-stage renal disease during a clinical trial with recombinant human erythropoietin (rHu-EPO). All the children showed a correction in both haematocrit and haemoglobin levels which was followed by a significant reduction in bleeding time. We also observed a significant increase in platelet count after both 6 and 12 weeks of therapy; at the same time mean platelet volume decreased and a normal platelet mass was maintained. The mean baseline platelet aggregation response to ADP was normal, but was decreased to collagen (P less than 0.05 vs normal control). Platelet production of thromboxane B2 in serum was also lower than normal controls. After correction of anaemia with rHu-EPO, platelet aggregation improved in patients with a decreased baseline response, and mean levels of thromboxane B2 became normal. In conclusion, the treatment with rHu-EPO improved haemostatic balance not only by correcting anaemia, but also by increasing platelet count and function.

Adolescent

Use of a radioimmunoassay for 5-hydroxytryptamine (5-HT) in thrombocytosis.

A decrease in intra-platelet 5-hydroxytryptamine (5-HT) may be a possible marker for primary thrombocytosis and there are several different methods for the measurement of platelet 5-HT content (e.g. fluorimetry, high-performance liquid chromatography and radioimmunoassay). The present study has shown that, in laboratories with radioprotected areas, radioimmunoassay of 5-HT is a simple method which correlates well with a standard fluorimetric technique and yields satisfactory results in patients with thrombocytosis.

Adult

Hemorheologic and coagulative pattern in hypercholesterolemic subjects treated with lipid-lowering drugs.

The effects on the coagulative and rheologic pattern of two lipid-lowering drugs, bezafibrate and simvastatin, were studied in 36 hypercholesterolemic subjects. Patients were randomly divided into two groups (18 subjects each) and received bezafibrate R 400 mg/day or simvatatin 10-40 mg/day over a twelve week period. Besides a decrease in plasma fibrinogen and fibrinopeptide A (p less than 0.001 both), bezafibrate induced a reduction of factor VIIc and VIIIc activity (p less than 0.001 both), while antithrombin 3 activity was increased (p less than 0.001) and the hemorheologic pattern was greatly improved (p less than 0.001). Simvastatin caused a slight decrease in factor VIIIc activity and a moderate reduction of beta-thromboglobulin. The efficacy of bezafibrate in reducing the activation of the coagulative cascade and improving the hemorheologic pattern has been confirmed; the peculiar triglycerides- and fibrinogen-lowering effect of the drug, not observed with simvastatin, could be responsible for these modifications.

Adult

Decrease of fibrinogen in patients with peripheral atherosclerotic disease by ticlopidine.

Ticlopidine (Ticlodone: CAS 55142-85-3) is able to develop a positive effect on claudication in patients affected by peripheral atherosclerotic disease (PAD). It is also known that ticlopidine decreases fibrinogen levels in plasma. 15 PAD patients treated with ticlopidine for 3 months were studied, evaluating the drug's effect both on maximum walking distance and on fibrinogen. Plasma fibrinogen as coagulable protein, fibrinogen antigen (Partigen method), 125I-fibrinogen survival, euglobulin lysis time and plasminogen were determined with the aim of clarifying if the decrease of plasma fibrinogen induced by ticlopidine is due to an increased destruction of a decreased production of the molecule. The normal levels of all tests before and after therapy both in ticlopidine treated patients and in the control group (acetylsalicylic acid + dipyridamol) indicate that the two hypotheses are not true. It is proposed that ticlopidine developing the known effect in decreasing the binding of fibrinogen to platelets induces a decrease only of activated fibrinogen.

Adult

[Treatment of hypercholesterolemic patients of different age with simvastatin: 1-year study].

Nowadays there is no direct evidence that lowering cholesterol may reduce the CHD in the elderly; however, several evidences suggest the potential benefit of a dietetic and/or pharmacologic intervention in healthy young-old hypercholesterolemics. In this study we evaluated the efficacy and tolerability of simvastatin, alone or in combination with cholestyramine, in two groups of patients (group A: age 30-55 years and group B: age 60-75 years) with primary hypercholesterolemia, over a 48-week period. In both groups Simvastatin induced a significant reduction in total and LDL cholesterol (p less than 0.001 both), with a decrease of the total/HDL cholesterol ratio (p less than 0.001). A reduction of the apo-B100 levels was also observed (respectively p less than 0.01 and p less than 0.001) with a significant improvement of the apo-B100/apo-A1 ratio (p less than 0.01). Simvastatin was well tolerated and free of remarkable side effects in both groups.

Adult

Thrombocytosis in young people: evaluation of 57 cases diagnosed before the age of 40.

Over the past 13 years 57 cases of primary thrombocytosis in young people have been studied. Only patients with a platelet count over 500 x 10(9)/liter and a follow-up longer than 2 years were considered. Thrombocytosis in young people represents approximately 25% of total cases referred to our department during this period. The most common causes are essential thrombocythemia (20 cases) and secondary thrombocytosis (22 cases). The highest platelet counts are found in essential thrombocythemia patients. Most of our patients were discovered by a fortuitous hematological examination. In contrast, 5 out of the polycythemic patients were recognized after a thrombosis. The same was true for 2 out of 20 essential thrombocythemia subjects. Four subjects (2 essential thrombocythemia and 2 secondary thrombocytosis) were diagnosed after hemorrhages. The overall survival was very good except for leukemic patients and thrombocytosis secondary to neoplasms. Vascular complications after diagnosis were scarce: 2 polycythemia vera patients showed bleedings during antiaggregating therapy. None of our patients developed epithelial cancer, malignant lymphoma or myelofibrosis. Vascular traumata seem more frequent in polycythemia vera regardless of age. Therefore, it seems useful to treat polycythemic patients, while no therapy seems to be indicated in other forms of thrombocytosis.

Adult

Benefits and risks of anemia correction with recombinant human erythropoietin in children maintained by hemodialysis.

Ten children with renal failure (age range 2 years 6 months to 18 years 9 months; median 11 years 10 months), maintained by long-term hemodialysis, had successful correction of their anemia after intravenous administration of recombinant human erythropoietin in a dosage escalating every 2 weeks (75 to 150 to 300 to 450 IU/kg/wk). Mean hemoglobin concentration increased from 6.4 +/- 0.9 to 11.5 +/- 1.0 gm/dl. Blood cell counts used to evaluate the correction of anemia were done after dialysis; this was especially important for children less compliant with water restriction. The higher hemoglobin concentration resulted in improvement of the quality of life, a greater tolerance for physical effort (exercise tolerance doubled and the ventilatory anaerobic threshold increased significantly), correction of some subclinical central nervous system abnormalities detected by evoked potentials testing, and reduction of bleeding time. Few side effects were noted; severe hypertension developed in one patient when postdialysis hematocrit was only 28%, and there were two episodes of hypertransaminasemia with no other evidence of liver dysfunction. We conclude that in children with renal failure the use of recombinant human erythropoietin to correct anemia is safe and strongly advisable, because of the resolution of many of the symptoms correlated with anemia.

Adolescent

Multiple, relapsing thrombosis in a young man with primary thrombocytosis.

We report the case of a relatively young man with multiple and fatal thrombosis associated with essential thrombocythaemia. The clinical and laboratory examinations performed before his death were in agreement with the diagnostic criteria proposed by PVSG. The autopsy revealed myocardial infarction and pulmonary embolisms. This case suggests that young patients with primary thrombocytosis should be treated with antiplatelet agents in spite of the absence of other thrombotic risks.

Humans

Platelet aggregation and pseudothrombocytopenia induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in type IIB von Willebrand's disease patient.

Our study shows that the thrombocytopenia described in type IIB von Willebrand's disease (vWd) after 1-desamino-8-D-arginine vasopressin (DDAVP) infusion is, at least partially, a pseudothrombocytopenia. There was a discrepancy in platelet counts in blood anticoagulated with EDTA (less than 10 x 10(3)/microliters) or citrate (55 x 10(3)/microliters) in one patient with type IIB vWd and chronic thrombocytopenia (80 x 10(3)/microliters) after DDAVP infusion. Furthermore, DDAVP induced a normalization of patient's prolonged bleeding time. Spontaneous platelet aggregation (SPA) observed in platelet-rich plasma before DDAVP infusion was inhibited completely by monoclonal antibodies which block binding of fibrinogen, vWf and fibronectin to GPIIb-IIIa. SPA was partially inhibited by a monoclonal antibody which blocks the binding of vWf to GPIb. After DDAVP, in contrast, SPA partially persisted in the presence of anti-GPIIb-IIIa monoclonal antibodies but was completely inhibited by anti-GPIb monoclonal antibody. Therefore GPIb and GPIIb-IIIa complex seem to play a different role in SPA before and after DDAVP infusion into type IIB vWd.

Adult

Variant Bernard-Soulier syndrome type bolzano. A congenital bleeding disorder due to a structural and functional abnormality of the platelet glycoprotein Ib-IX complex.

We have studied a patient with a congenital bleeding disorder and phenotypic manifestations typical of Bernard-Soulier syndrome, including giant platelets with absent ristocetin-induced von Willebrand factor binding. Two monoclonal antibodies reacting with distinct epitopes in the amino-terminal domain of the alpha-chain of glycoprotein (GP) Ib were used to estimate the number of GP Ib molecules on the platelet membrane. In the patient, binding of one antibody (LJ-Ib10) was approximately 50% of normal, while binding of the other (LJ-Ib1) was absent. Binding of both antibodies was reduced to approximately 50% of normal in the mother and one sister of the propositus, and their platelets exhibited approximately 70% of normal von Willebrand factor binding. Immunoblotting studies confirmed the presence of GP Ib alpha, as well as GP IX, in patient platelets. Antibody LJ-Ib10, but not LJ-Ib1, could immunoprecipitate the patient's GP Ib alpha from surface-labeled proteins. Thus, platelets from the propositus contained a structurally and functionally altered GP Ib-IX complex lacking a specific antibody epitope and the ability to bind von Willebrand factor. In contrast, the binding of human alpha-thrombin to the patient's platelets was normal, and three classes of binding sites with high, intermediate, and low affinity could be detected. These studies define a distinct variant form of Bernard-Soulier syndrome and provide evidence, based on a naturally occurring mutant molecule, that the amino-terminal region of GP Ib alpha contains a von Willebrand factor-binding domain distinct from the high affinity thrombin-binding site. Use of different monoclonal antibodies with distinct epitope specificities appears to be essential for a correct identification of variant Bernard-Soulier syndrome.

Antibodies, Monoclonal