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Biomedical subjects

F Salvati

Publications and source records attributed to F Salvati.

At least 19 recordsLinked to original sources
PubMed2005

Inhibition of thromboxane biosynthesis by triflusal in type 2 diabetes mellitus.

Triflusal is an antiplatelet drug related to aspirin, with different pharmacological properties and a lower haemorrhagic risk. We aimed at comparing their effects on platelet and endothelial activation in type 2 diabetes mellitus (T2DM). In a randomized, double-blind, parallel group study, we compared the effects of three daily regimens (300, 600, and 900 mg) of triflusal, and aspirin (100mg/day) on urinary 11-dehydro-thromboxane (TX)B(2), index of in vivo platelet activation, ex vivo platelet function using the analyzer PFA-100, plasma von Willebrand factor (vWF), P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and serum nitrite and nitrate (NO(2)(-)+NO(3)(-)) in 60 T2DM patients. Triflusal induced a dose-dependent reduction in 11-dehydro-TXB(2) and a prolongation of closure time in the presence of collagen plus epinephrine (Coll/Epi-CT). The effects of the highest triflusal dose were not different from those of aspirin. The closure time in the presence of collagen plus ADP (Coll/ADP-CT), ICAM-1, VCAM-1, and NO(2)(-)+NO(3)(-) were not modified either by triflusal or aspirin. Plasma P-selectin and vWF were reduced by triflusal but not by aspirin. In T2DM triflusal causes a profound inhibition of platelet TXA(2) biosynthesis in vivo, acting on different targets involved in the platelet-endothelial cell interactions.

Adult↗
PubMed2001

Role of platelet surface receptor abnormalities in the bleeding and thrombotic diathesis of uremic patients on hemodialysis and peritoneal dialysis.

BACKGROUND: Patients with chronic renal failure suffer from bleeding diathesis and a tendency to accelerated atherosclerosis. Altered platelet function plays a well defined role in the hemorrhagic complications of these patients and has a probable impact on atherothrombotic disease in uremia. In this study we investigated the expression of platelet surface receptors, the glycoprotein GPIb (receptor for von Willebrand Factor(vWF) and GPIIb/IIIa (receptor for fibrinogen) in patient with chronic renal failure in pre-dialysis status, under hemodialysis and peritoneal dialysis treatment, in order to assess the impact of the abnormal receptorial status of uremic platelets on the clinical manifestations of hemostatic alterations in uremic patients. METHODS: Thirty-seven normal healthy subjects (controls = Group A), 18 patients with mild chronic renal failure (creatinine = 1.8 +/- 0.5 mg% - Group B), 15 patients with advanced renal failure (creatinine = 5.4 +/- 2. 1 mg% - Group C), 18 hemodialysis patients (Group D) and 11 peritoneal dialysis patients (Group E) were included in the study. The expression of platelet surface receptors GPIb and GPIIb/IIIa was investigated with monoclonal antibodies CD42 and CD41 (Immunotech, Marseille, France) and a FACScan flowcytometer (Becton-Dickinson, USA). RESULTS: Mean values of GPIb glycoprotein (mean flow +/- SD) were: group A = 48.14 +/- 9.31; group B = 40.48 +/- 8.18 (p < 0.005); group C = 34.05 +/- 7.55 (p < 0.0005) versus group A; p = 0.025 versus group B); group D = 34.51 +/- 7.22 (p < 0.0005 versus group A; p = 0.025 group B and p = ns versus group C); group E = 26.34 +/- 4.06 (p < 0.0005 versus group A, p < 0.0005 versus group B, p < 0.005 versus groups C and D). Mean values of glycoprotein GPIIb/IIIa were: group A = 375.32 +/- 90.58; group B = 398.48 +/- 54.26 (p = ns); group C = 426.86 +/- 52.78 (p < 0.025 versus group A; p = ns versus group B); group D = 425.17 +/- 75.03 (p < 0.025 versus group A; p = ns versus groups B and C); group E = 336.39 +/- 43.26 (p = ns versus group A; p < 0.005 versus group B, p < 0.0005 versus group C and p < 0.001 versus group D). CONCLUSIONS: Our data confirm the receptorial defect of glycoprotein GPIb (the receptor for vWF) on the surface of uremic platelets: a negative correlation between serum creatinine and the expression of glycoprotein GPIb was found. The defect was not corrected by hemodialysis and/or peritoneal dialysis. Hemodialysis and peritoneal dialysis have a different impact on the expression of GPIIb/IIIa glycoprotein (the receptor for vWF): peritoneal dialysis seems to have a more favourable effect by restoring normal values of the expression of this membrane integrine. Theoretically the data could be correlated to the better biocompatibility of the peritoneal dialysis and to more favorable clinical behaviour in terms of accelerated atherosclerosis and athero-thrombotic complications in the uremic patients with end stage renal disease. Finally the abnormalities of platelet surface receptors may play a main role in the hemostatic alterations of uremic patients.

Blood Platelets↗
PubMed2000

Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: New effective chemotherapy is needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC. PATIENTS AND METHODS: Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m(2)) or a combination of paclitaxel (175 mg/m(2), 3-hour infusion) and cisplatin (80 mg/m(2)) every 21 days. RESULTS: Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P=.028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P=.026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P=.862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms. CONCLUSION: This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.

Adult↗
PubMed2000

Ambamustine in the second-line treatment of patients with small-cell lung cancer: a phase II Fonicap study.

Despite a high probability of response to first-line chemotherapy, most patients with small-cell lung cancer (SCLC) will eventually have progression of their disease because of the development of resistant disease. Second-line testing of new drugs is an accepted research strategy in SCLC. In this context, the Italian Lung Cancer Task Force (FONICAP) has tested a new synthetic bifunctional alkylating agent, Ambamustine, with preliminary evidence of activity in other solid tumors. Patients with measurable SCLC, progressive after one first-line chemotherapy regimen (either "sensitive" or "refractory"), were eligible for the study. Ambamustine was administered at the dose of 2 mg/kg as a 1-hour intravenous infusion on day 1 every 21 days. The dose was to be increased to 3 mg/kg if no grade IV toxicity and complete hematologic recovery had occurred by day 22. Sample size was calculated according to a two-stage optimal Simon's design. Seventeen patients were entered into the study. Twelve patients were refractory to prior chemotherapy; 12 had extensive disease; the median age was 64 years (range: 46-75 years) and the median performance status was 1. Among 13 patients who received more than one cycle, 9 patients could increase Ambamustine dose from 2 to 3 mg/kg. No objective response was observed: one patient obtained a 50% regression of the primary tumor with contemporary disease progression in the liver and was qualified as having progressive disease. The treatment was well tolerated: grade IV leukopenia occurred in only 1 patient; grade III anemia occurred in 17.6%, grade III leukopenia in 11.8%, and grade III thrombocytopenia in 23.5%. Nonhematologic toxicity was minimal. Ambamustine, at the dose and schedule used in this study, is well tolerated in pretreated patients with SCLC but has no significant antitumor activity in this unfavorable group of patients.

Aged↗
PubMed1998

Cisplatin-vindesine-mitomycin (MVP) vs cisplatin-ifosfamide-vinorelbine (PIN) vs carboplatin-vinorelbine (CaN) in patients with advanced non-small-cell lung cancer (NSCLC): a FONICAP randomized phase II study. Italian Lung Cancer Task Force (FONICAP).

In the present multicentre randomized phase II trial, the activity and toxicity of three platinum-based combination regimens for the treatment of advanced non-small-cell lung cancer (NSCLC) were evaluated. The three regimens were: MVP (mitomycin-C 6 mg m(-2) on day 1, vindesine 3 mg m(-2) on days 1 and 15, and cisplatin 80 mg m(-2) on day 1 every 28 days), PIN (cisplatin 80 mg m(-2) day 1, ifosfamide 3 g m(-2) day 1 and vinorelbine 25 mg m(-2) day 1 and 8 every 21 days) and CaN (carboplatin 350 mg m(-2) day 1 and vinorelbine 25 mg m(-2) days 1 and 8 every 28 days). A total of 140 chemotherapy-naive patients entered the study; 49 patients were treated with MVP, 48 with PIN and 43 with CaN. Sixty-seven per cent of the patients had stage IV disease. Response rates, calculated on an 'intention to treat' basis, were as follows: MVP, 14.3% (95% CI 5.94-27.2%); PIN, 16.7% (95% CI 7.4-30.2%); and CaN, 14% (95% CI 5.3-27.9%). The overall median survivals were 256, 269 and 243 days for patients treated with MVP, PIN and CaN respectively. Myelosuppression was the most frequent toxicity: grade 3-4 leucopenia was observed in 14.3%, 25% and 18.6% of patients treated with MVP, PIN and CaN respectively. This multicentre phase II randomized trial shows that MVP, PIN and CaN can be administered on an outpatient basis with acceptable toxicities. Unfortunately, the three regimens showed an activity significantly lower than that reported in previous single-institution phase II trials.

Adult↗
PubMed1997

Cisplatin-gemcitabine combination in advanced non-small-cell lung cancer: a phase II study.

PURPOSE: The nucleoside analog, gemcitabine, has shown activity as a single agent in the treatment of metastatic non-small-cell lung cancer (NSCLC). Its combination with cisplatin in preclinical models suggested synergy between the two drugs. The aim of the study was to evaluate the clinical efficacy and toxicity of the cisplatin-gemcitabine combination in advanced NSCLC. PATIENTS AND METHODS: Forty-eight consecutive previously untreated NSCLC patients entered the trial from January to June 1994. The median age was 60 years (range, 37 to 70) and performance status (PS) was 0 or 1; 22 patients had unresectable stage III disease (21 stage IIIB and one stage IIIA) and 26 had stage IV disease. Gemcitabine 1 g/m2 was administered weekly (days 1, 8, and 15) followed by a 1-week rest and cisplatin 100 mg/m2 on day 2 of each 28-day cycle. Survival and response were determined in accordance with the intention-to-treat principle in all enrolled patients. RESULTS: Of 48 assessable patients, one (stage IV) had a complete response (CR) and 25 achieved a partial response (PR). The overall response rate was 54% (95% confidence interval [CI], 40% to 68%). Thrombocytopenia was the main side effect, with 52% of patients experiencing grade III to IV toxicity, which was usually short-lived and responsible for the omission of gemcitabine administration on day 15 in 50% of chemotherapy courses. The median survival time was 61.5 weeks (95% CI, 40 to 71). CONCLUSION: The combination of gemcitabine and cisplatin induced a high response rate in both stage IIIB and IV NSCLC, with modest side effects. The regimen deserves further careful evaluation in a phase III prospective randomized trial.

Adult↗
PubMed1996

Arteriovenous fistula obstruction and expression of platelet receptors for von Willebrand factor and for fibrinogen (glycoproteins GPib and GPiib/iiia) in hemodialysis patients.

Platelet surface receptors for von Willebrand factor and for fibrinogen (glycoproteins GPIb and GPIIb/IIIa) were studied with monoclonal antibodies CD42 and CD41 and cytofluorometry in 31 healthy subjects, 10 hemodialysis patients with no A-V fistula obstruction (patent original fistula), 10 hemodialysis patients with frequent A-V fistula obstruction (more than twice), 12 patients with mild chronic renal failure (creatinine 1.75 +/- 0.40 mg/100 ml), 11 patients with advanced chronic renal failure (creatinine 5.62 +/- 1.22 mg/100 ml), and 10 patients with end-stage renal disease (ESRD) treated with peritoneal dialysis. There was a significant increase of platelet surface glycoproteins GPIb and GPIIb/IIIa in the population of hemodialysis patients with frequent A-V fistula obstruction. The expression of these platelet receptors might be related to the prothrombotic tendency of a group of patients with ESRD, who suffer more occlusive and thrombotic events of the A-V fistula. This group of patients may also have a higher frequency of systemic thrombotic and atherosclerotic complications.

Antibodies, Monoclonal↗