Paolo Bordin

Factors associated with cognitive impairment among older Italian inpatients

OBJECTIVE: To examine the association of cognitive impairment with educational, demographic, and nutritional variables in older hospitalized people.

Low Density Lipoprotein-Apheresis Decreases Oxidized Low Density Lipoproteins and Monocyte Adhesion to Endothelial Cells

The mutual interaction between monocytes and low density lipoprotein (LDL) in atherogenesis prompted a test of the hypothesis that LDL-apheresis could reduce the adhesive properties of monocytes to endothelium; and therefore interfere with a key mechanism in atheroma formation. Five patients affected by heterozygous familial hypercolesterolemia were studied. All patients received LDL-apheresis treatment with selective adsorption of LDL-cholesterol on dextran-sulphate columns. Low density lipoprotein particles were isolated by sequential preparative ultracentrifugation and subfractionated by ion exchange high performance liquid chromatography. Thiobarbituric acid reacting products of lipid peroxidation were measured fluorometrically. Vitamin E was estimated by high performance liquid chromatographic technique. Monocytes were isolated from patients blood before and 1 day after LDL-apheresis by Percoll gradient. The blood samples for monocyte adhesion were drawn from control subjects for 2 consecutive days. The adhesion of monocytes to an endothelial monolayer was evaluated by assaying the peroxidase content of the adherent monocytes. Low density lipoprotein-apheresis reduced total cholesterol (−65%; p < 0.01), LDL-cholesterol (−75%; p < 0.01), triglycerides (−51%; p < 0.05), and fibrinogen (−28%; p < 0.01). With LDL-apheresis treatment, a reduction of 54% in oxidized LDLs was observed; vitamin E concentration significantly increased in LDLs ( + 14.2%; p < 0.05). The monocyte adhesion decreased by approximately 61% after apheresis; the variation became statistically significant (−65%; p < 0.01) when endothelial cells were stimulated by lipopolysaccaride.

Activation of coagulation by a LDL-apheresis device.

LDL-apheresis often induces an almost constant and progressive increase of the differential pressure of plasma flowing through the dextran sulphate cellulose column, reducing the efficacy of the treatment. On two occasions we were able to identify a fibrin plug by immunofluorescence. Our aim was to verify the modification of some coagulation indicators in patients undergoing LDL-apheresis and whether an activation of coagulation occurs in the LDL-apheresis device. Blood samples were obtained from six patients with familial hypercholesterolaemia who were undergoing LDL-apheresis. During the same session further blood/ plasma samples were taken from the LDL-apheresis device at different sites and at different volumes of filtered blood. In patients after LDL-apheresis the following modifications were found: a 25% decrease of fibrinogen and a slight increase in F1 + 2 plasma levels. No relevant changes in thrombin-antithrombin complexes and fibrinopeptide A plasma levels were noted. In the LDL-apheresis device the main results were: (a) fibrinogen was trapped in the dextran sulphate cellulose column in the early phases; (b) activation of coagulation was recognisable in the plasma separator during the procedure and progressively increased with duration of LDL-apheresis; (c) thrombin-antithrombin complexes, formed in the plasma separator, were retained by the dextran sulphate cellulose column. In conclusion, LDL-apheresis activates coagulation in the device. Shortening cycle time or using nafamostat mesilate as an anticoagulant, could be interesting alternatives for improving the procedure.

Efficacy and safety of simvastatin in current clinical practice: the italian family physician simvastatin study

Abstract The availability of modern hypocholesterolemic drugs that are easy to handle may give any physician the ability to treat patients with elevated levels of total serum cholesterol and low-density lipoprotein (LDL)cholesterol. The Italian Family Physician Simvastatin Study was an open-label, noncomparative, diet-controlled, multicenter, post-marketing surveillance study carried out by nonspecialist physicians to evaluate the efficacy and safety of simvastatin in the current clinical practice. The study evaluated 5348 patients (2887 men [mean age, 61 ± 7 years]) and 2461 women [mean age, 55 ± 11 years]) with primary hypercholesterolemia. After a 10-week washout period, the selected patients were actively treated for 24 weeks with simvastatin 10 mg administered once a day in the evening. The dose was increased, if necessary, at the 12-and 18-week visits, to 20 or 40 mg/d. A total of 5081 patients (95%) completed the study; 195 patients (3.6%) were lost at follow-up and the other 72 (1.3%) discontinued the study because of the occurrence of adverse effects. Of the 5081 patients, 3691 (72.6%) received 10 mg/d simvastatin, 1159 (22.8%) 20 mg/d, and 202 (4.0%) 40 mg/d; in the others a personalized dose of the drug (range, 5 to 30 mg/d) was given. Simvastatin produced significant decreases in total serum cholesterol of 30%, LDL cholesterol of 41%, and triglyceride levels of 14%, and significant increases in high-density lipoprotein (HDL) cholesterol of 13%. The efficacy goal of total serum cholesterol level ( 3 times the upper limit of normal) were recorded only in 0.7% of all control visits. Serum creatine kinase (CK) did not significantly change and serum elevations >10 times the upper limit of normal without muscle symptoms was observed in 0.4% of all patients, whereas myalgia without concomitant increase of CK was reported by 0.6% of the 5081 patients. On the whole, 267 clinical adverse effects occurred in 235 patients (4.4%), in a dose-dependent manner. Simvastatin, when studied in the current clinical practice of general practitioners, produced a marked decrease in LDL cholesterol and improved the global lipoprotein profile with infrequent, minor, dose-dependent side effects.

100. Activation of coagulation by a LDL-apheresis device

LDL-apheresis often induces an almost constant and progressive increase of the differential pressure of plasma flowing through the dextran sulphate cellulose column, reducing the efficacy of the treatment. On two occasions we were able to identify a fibrin plug by immunofluorescence. Our aim was to verify the modification of some coagulation indicators in patients undergoing LDL-apheresis and whether an activation of coagulation occurs in the LDL-apheresis device. Blood samples were obtained from six patients with familial hypercholesterolaemia who were undergoing LDL-apheresis. During the same session further blood/plasma samples were taken from the LDL-apheresis device at different sites and at different volumes of filtered blood. In patients after LDL-apheresis the following modifications were found: a 25% decrease of fibrinogen and a slight increase in F1 +2 plasma levels. No relevant changes in thrombin—antithrombin complexes and fibrinopeptide A plasma levels were noted. In the LDL-apheresis device the main results were: (a) fibrinogen was trapped in the dextran sulphate cellulose column in the early phases; (b) activation of coagulation was recognisable in the plasma separator during the procedure and progressively increased with duration of LDL-apheresis; (c) thrombin—antithrombin complexes, formed in the plasma separator, were retained by the dextran sulphate cellulose column. In conclusion, LDL-apheresis activates coagulation in the device. Shortening cycle time or using nafamostat mesilate as an anticoagulant, could be interesting alternatives for improving the procedure.

Effect of ciprofibrate in patients with primary hypercholesterolemia : a 6-year pilot study

Abstract The efficacy and tolerability of a single daily dose of ciprofibrate, a fibrate derivative with a prolonged half-life, were evaluated in an open-label study with 6 years of follow-up. The study included 26 patients (12 men, 14 women; mean age, 56 years) with primary type IIa (n = 19) or type IIb (n = 7) hypercholesterolemia. Patients received 100 mg/d ciprofibrate for up to 6 years (mean, 36 months). Comparing baseline and final values (means of the last three assessments) in each patient, independent from length of treatment, total and low-density lipoprotein and cholesterol decreased from 312 ± 40 mg/dL to 250 ± 42 mg/dL (−20%) ( P ⩽ 0.001) and from 210 ± 37 mg/dL to 172 ± 40 mg/dL (−18%) ( P ⩽ 0.001), respectively. Ciprofibrate reduced serum triglyceride levels from 202 ± 152 mg/dL to 116 ± 52 mg/dL (−43%) ( P ⩽ 0.0001) and increased high-density lipoprotein cholesterol levels from 49 ± 10 mg/dL to 53 ± 11 mg/dL (+8%) ( P ⩽ 0.01). Hematochemical safety parameters were monitored during the whole study. Alkaline phosphatase significantly ( P ⩽ 0.01) decreased after 3 months (from 77 ± 22 U/L to 55 ± 15 U/L) and remained constant thereafter. No significant changes were noted in serum transaminases and creatine kinase levels. The frequency of clinical adverse events was negligible, and compliance with therapy was good. In conclusion, 100 mg/d of ciprofibrate, administered for 6 years to patients with primary isolated or mixed hypercholesterolemia, was effective and well tolerated. Further controlled studies in larger groups of patients are needed to fully confirm these promising results.