Search PubMed⌕ Search

Biomedical subjects

G Perani

Publications and source records attributed to G Perani.

At least 19 recordsLinked to original sources
PubMed1996

Protective effects of carvedilol, a vasodilating beta-adrenoceptor blocker, against in vivo low density lipoprotein oxidation in essential hypertension.

Low density lipoprotein (LDL) oxidation plays a crucial role in the development and progression of atherosclerosis and is enhanced in patients with essential hypertension. This finding has stimulated a search for antihypertensive drugs with high intrinsic antioxidant properties. We investigated the antihypertensive and antioxidant effects of carvedilol, a new vasodilating beta-adrenoceptor blocking agent in a group of patients with mild to moderate essential hypertension after 4-month treatment. Carvedilol administration markedly increased the resistance to oxidation of LDL isolated from treated patients to values comparable to those of control, nonhypertensive subjects. This effect was achieved despite a significant loss in LDL-associated vitamin E. The increased resistance of LDL to oxidation promoted by carvedilol was not related to the normalization of previously increased blood pressure (BP). Indeed, the administration of other conventional antihypertensive drugs, capable of decreasing arterial BP but without high intrinsic antioxidant properties, to a control group of matched hypertensive patients failed to ameliorate LDL oxidation parameters. Carvedilol treatment also reduced the extent of in vivo LDL oxidation, as reflected by the decrease in antioxidized LDL autoantibody titer. This effect as well was detected only in the group of carvedilol-treated hypertensive patients and not after the simple reduction in BP obtained with antihypertensive drugs different from carvedilol.

Adrenergic beta-Antagonists↗
PubMed1996

Effects of systemic treatment with statins on skin barrier function and stratum corneum water-holding capacity.

BACKGROUND: Topical application of inhibitors of HMGCoA reductase, the rate-limiting enzyme of cholesterol synthesis, has been shown to induce impairment of barrier function. OBJECTIVE: Assessing whether oral administration of statins used for reducing blood levels of cholesterol induces functional changes in stratum corneum barrier. MATERIALS AND METHODS: 69 subjects of both sexes under-going treatment for hypercholesterolemia (mean age 48 +/- 11 years) entered the study; 43 had been treated with simvastatin and 11 with pravastatin for 6 months; 15 only on dietary regimen served as controls. Efficiency of stratum corneum water barrier was evaluated by transepidermal water loss (TEWL) measurement using an evaporimeter; water-holding capacity of the stratum corneum was assessed by the sorption-desorption test measured by capacitance. Statistical analysis was performed using ANOVA. RESULTS: No differences were found between the groups (simvastatin, pravastatin, diet) concerning both basal TEWL and the dynamic of water binding in the stratum corneum. CONCLUSIONS: Prolonged treatment with cholesterol-lowering drugs based on inhibition of HMGCoA reductase does not alter the permeability barrier of the skin.

Administration, Oral↗
PubMed1995

[Oxidation of low-density lipoproteins. Correlation between reduced resistance in vitro and increased oxidation in vivo].

OBJECTIVES: The oxidation of low-density lipoproteins has been recently proposed as one of the critical factors in promoting atherogenesis. This process results from the balance between the prooxidant stimuli and the endogenous antioxidants present in LDL and strictly depends on the concentration of oxidizable substrates, namely unsaturated fatty acids. METHODS: Twelve male hypertriglyceridaemic patients were investigated before and after oral supplementation with omega-3 polyunsaturated fatty acids (PUFA) and compared with eighteen untreated healthy matched control subjects. The plasma lipid profile was measured in all patients. LDL oxidation was evaluated as both the susceptibility to in vitro oxidation and the presence of plasma anti-oxidized LDL antibodies (as a marker for in vivo oxidation). RESULTS: Omega-3-fatty acid supplementation caused a significant reduction in plasma triglyceride level (267 +/- 38 vs 375 +/- 33 mg/dl, p < 0.01) and decreased the resistance of LDL to oxidation as revealed by an early and accelerated generation of conjugated dienes following exposure to CuSO4 (105.3 +/- 7 vs 133 +/- 9.3 min, p < 0.01). Moreover, the concentration of the antioxidant vitamin E in LDL was slightly but significantly decreased at the end of the treatment (2.59 +/- 0.19 vs 2.89 +/- 0.17 nmol/mg LDL, p < 0.05), but its efficiency in preventing LDL oxidation was unaltered. Furthermore, a marked increase of the plasma anti-oxidised LDL antibody titre was found in nearly all patients at the end of the treatment (2.08 +/- 0.48 vs 1.37 +/- 0.2 anti-oxidised/anti-native LDL antibody ratio, p < 0.001). CONCLUSION: These results indicate that PUFA supplementation decreases the resistance of LDL to in vitro oxidation and that this decreased resistance is accompanied by an enhanced LDL oxidation in vivo.

Adult↗
PubMed1995

Efficacy and pharmacokinetics of simvastatin in heart transplant recipients.

OBJECTIVE: To evaluate the efficacy and safety of simvastatin administered to a group of heart transplant patients receiving triple-drug immunosuppressive therapy. We also assessed the potential pharmacokinetic interaction between simvastatin and cyclosporine by comparing mean plasma concentrations of simvastatin beta-hydroxy acid, the major metabolite of the drug, in a group of heart transplant patients treated with cyclosporine and in a control group of patients who had not received heart transplants. Both groups received long-term (> 6 wk) simvastatin therapy. DESIGN: We monitored hyperlipidemia in 20 hypercholesterolemic heart transplant patients receiving simvastatin 10 mg/d and triple-drug immunosuppressive therapy. Changes in laboratory results before and after 4 months of simvastatin therapy were considered. The same laboratory data were monitored in a control group of 20 nonhypercholesterolemic heart transplant patients who were not treated with simvastatin but were receiving triple-drug immunosuppressive therapy. Plasma concentrations of simvastatin beta-hydroxy acid were measured in 14 hypercholesterolemic patients, 7 of whom had received heart transplants and 7 who had not. SETTING: The Division of Cardiology and the First Medical Clinic for the clinical study, as well as the Department of Pharmacology for the pharmacokinetic analysis. PARTICIPANTS: Forty heart transplant patients and 7 hypercholesterolemic nontransplant patients. MAIN OUTCOME MEASURES: Effectiveness of simvastatin was determined by comparing cholesterol and lipoprotein plasma concentrations in 20 patients who underwent heart transplant and were treated with simvastatin for 4 months. The safety of the drug was determined by analyzing changes in laboratory results in the treated group and in the control group, both those who had received heart transplants and those who had received immunosuppressive therapy. RESULTS: After 4 months of simvastatin therapy, total cholesterol decreased by 12.5% and low-density lipoprotein cholesterol decreased by 21.3%. The only statistically significant laboratory change was an increase of 28.7% in the alanine aminotransferase concentrations. Plasma concentrations of simvastatin beta-hydroxy acid were higher in heart transplant patients than in those who had not received heart transplants, the control group. CONCLUSIONS: Low-dosage simvastatin treatment seems to be safe and sufficiently effective to decrease cholesterol concentrations. Concomitant treatment with immunosuppressive therapy (primarily cyclosporine) in heart transplant patients appeared to cause a reduced metabolic clearance of simvastatin from the plasma. More extensive studies on the interaction between simvastatin and cyclosporine are needed to understand the marked variability found in the response to simvastatin.

Adult↗
PubMed1994

Enhanced LDL oxidation in uremic patients: an additional mechanism for accelerated atherosclerosis?

Since oxidized low-density lipoprotein (LDL) is more atherogenic than native LDL, LDL oxidation was investigated in uremic patients who often develop accelerated atherogenesis. Three groups of uremic patients were studied (10 on predialysis conservative therapy, 11 on repetitive hemodialysis, 13 on peritoneal dialysis) and compared with seventy matched controls. LDL oxidation was evaluated in all patients as: (i) the susceptibility to in vitro oxidation (by measuring the resistance to Cu(++)-induced formation of conjugated dienes), (ii) vitamin E concentration in LDL, and (iii) presence of plasma anti-oxidized LDL antibodies, expressed as the ratio anti-oxLDL/anti-nativeLDL antibodies. The lipid profile was studied in all patients. Vitamin E concentration did not differ between the various groups, although LDL from uremic patients appeared more susceptible to in vitro and in vivo oxidation (as demonstrated by an earlier generation of conjugated dienes and by the presence of an higher antibody ratio) compared to control subjects. Subclass analysis of the different patients revealed that peritoneal dialysis treatment ameliorated the oxidation markers. However, a prolonged dialytic treatment caused a decrease in vitamin E concentration in LDL and increased their susceptibility to oxidation.

Arteriosclerosis↗
PubMed1994

Metabolic risk factors in white coat hypertensives.

Metabolic disturbances such as hyperinsulinaemia, dislipoproteinaemia and glucose intolerance are often associated with essential hypertension and markedly affect cardiovascular morbidity in hypertensive patients. In order to shed some light on the prognostic significance of white coat hypertension (raised clinic and normal ambulatory blood pressure), we compared the metabolic profile in a group of white coat and sustained previously untreated hypertensives. We studied 84 newly detected hypertensive patients (49 men, 35 women, 47 +/- 8 years, range 28-59 years). Subjects with obesity (BMI > 30), NIDDM and target organ damage were excluded. Ambulatory blood pressure monitoring was performed by SpaceLabs 90207-31. Total cholesterol and triglycerides, LDL-cholesterol, HDL-cholesterol (HDL-C) and subclasses HDL2 and HDL3 cholesterol as well as apolipoprotein A1 and B were measured in fasting plasma. Glucose and insulin were determined in fasting and postload (glucose 75 g plasma. Twenty patients (24%, 8 men and 12 women) were classified as white coat hypertensives. No differences in age, BMI and waist to hip ratio were observed between white coat and sustained hypertensive patients. Plasma glucose and lipoprotein levels were similar in the two groups. Fasting and postload insulin levels were significantly lower in white coat hypertensives (fasting insulin 7.1 +/- 2.9 vs. 12 +/- 8.6 microU/ml, P < 0.02; insulin 120 minutes 48 +/- 27 vs. 65 +/- 41 microU/ml, P < 0.05); glucose/insulin rate was higher in white coat than in sustained hypertensive patients (15 +/- 7 vs. 11 +/- 7, P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Low-density lipoprotein oxidation and antioxidized LDL antibodies in peritoneal dialysis patients.

Due to the potential atherogenic effects of oxidized low-density lipoproteins (LDLs), LDL oxidation was studied in a group of uremic patients on chronic peritoneal dialysis. The results were compared with those obtained in a group of 70 controls, 10 uremic patients on predialytic conservative therapy, and 11 patients on repetitive hemodialysis. LDL oxidation was evaluated in all subjects as the susceptibility to in vitro oxidation (monitoring the resistance to Cu(2+)-induced formation of conjugated dienes, lag-phase minutes) and the presence of plasma antioxidized LDL antibodies, expressed as the ratio anti-ox-LDL/antinative LDL antibodies. Vitamin E (main antioxidant agent) content in LDLs was also measured and the lipid profile studied. No significant changes in vitamin E concentration were found, although LDLs from uremic patients appeared more susceptible to in vitro and in vivo oxidation (as demonstrated by an earlier production of conjugated dienes and by the presence of a higher antibody ratio), as compared to control subjects. Analysis of the different groups of uremic patients revealed that peritoneal dialysis, not hemodialysis, significantly ameliorated the oxidation markers. However, prolonged treatment with peritoneal dialysis caused a decrease in vitamin E concentration in LDLs and increased their susceptibility to oxidation.

Antibodies↗
PubMed1993

[Effectiveness and tolerability of simvastatin in subjects with primary hypercholesterolemia. Multicenter study].

The efficacy and safety of simvastatin were evaluated in an open multicenter study over a 24-week period. One hundred seventy-two patients (91 men, 81 women) with primary hypercholesterolemia (mostly polygenic) were enrolled in 14 Centers in Northern Italy. The mean age was 55.8 +/- 9.7 years and the mean baseline total cholesterol level was 305 +/- 59 mg/dL. After 4 weeks on an AHA step 1 diet, patients who met the inclusion criterion (total cholesterol > or = 250 mg/dL) were given simvastatin 10 or 20 mg in the evening. The dose could be titrated up to a maximum of 40 mg o.d. at week 6 and 12. No dose titration was allowed after week 12. One hundred forty-nine patients (86.6%) completed the study according to the protocol, 2 (1.2%) were withdrawn from the study because of adverse events not related to the drug, 21 (12.2%) were unavailable for follow-up. Simvastatin treatment was associated with a sustained dose-related reduction in total and LDL cholesterol (-28% and -39% respectively at the end of the study). Triglycerides showed a significant descending trend (-16% at week 24) and HDL-C increased by 9%. Apolipoproteins were measured in only 25 patients: apo B was reduced by 30% and apo A1 increased by 9%. Clinical side effects were not relevant. Mean levels of GOT, GPT and CPK significantly increased after 6 weeks on simvastatin, but remained stable and at any rate ioitlin the normal range thereafter. Eight patients (5.4%) experienced small transaminase level elevations (< 3ULN) and six (4%) small CPK elevations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Left ventricular function after reversal of myocardial hypertrophy in systemic hypertension, and response to acute increase of afterload by cold pressor test.

Using digitized M-mode echocardiography, the left ventricular (LV) response to acute increase in blood pressure after regression of myocardial hypertrophy due to an effective antihypertensive treatment was evaluated. Fifteen hypertensive patients with basal LV hypertrophy (LV mass greater than 230 g, and normal LV diastolic diameter) and normal LV mass after 3 to 4 months of treatment with angiotensin-converting enzyme inhibitors were selected for study. Subjects performed a cold pressor test before and after therapy. LV systolic function was normal in all subjects. LV diastolic function (impaired at basal evaluation in 13 subjects) improved after therapy in all subjects, with normalization in 10. Before treatment, the cold pressor test induced significant increases in blood pressure and heart rate without changes in LV parameters. After regression of hypertrophy, the cold pressor test induced increases in hemodynamic parameters comparable to those of the basal test, and LV parameters remained unchanged. Our results indicate that regression of myocardial hypertrophy induced by angiotensin-converting enzyme inhibitors does not impair the ability of the left ventricle to face acute increases in afterload. The improvement in LV diastolic function (found at rest after reversal of hypertrophy) persists during the cold pressor test, which confirms that it is primarily due to LV mass reduction and is not simply a consequence of decrease in afterload induced by treatment.

Adult↗
PubMed1991

Transdermal estradiol substitution therapy for the induction of puberty in female hypogonadism.

Fifteen patients aged 14.5-27.3 years (mean +/- SE 18.8 +/- 0.9) with pubertal development failure underwent replacement therapy with estradiol (E2) using a transdermal therapeutic system (TTS). Fourteen of them were affected by hypogonadotropic hypogonadism (11 with thalassemia major, 3 with multiple pituitary hormone deficiency), the 15th patient had an asymmetric gonadal dysgenesis (karyotype 45, X 0/46, XY). Two sizes (5 and 10 cm2) of E2 TTS, delivering respectively 25 and 50 micrograms of E2 a day for 3 1/2 days, were used in this study. All patients were initially given the lower dose of 25 micrograms, twice weekly for 3 weeks each month; 6 months after starting therapy, 5-10 mg oral medroxyprogesterone acetate (MPA) daily was added during the third week. Later, the following sequence was used: 25 micrograms E2 TTS (twice weekly), on days 1 through 14, and 50 micrograms E2 TTS (twice weekly), on days 15 through 25 of each month. On days 15 through 25, 5 mg daily of MPA were administered orally. The period of treatment ranged from 0.5 to 3 years. Breast development was obtained in all cases. The vaginal maturation index rose. Ultrasonography showed an increase of uterine size and uterine shape became of pubertal type. Withdrawal bleeding occurred in all patients. Plasma E2 levels rose to normal levels, estrone (E1) levels increased slightly. No change in plasma SHBG levels was observed. Urinary E2, E1 and estriol rose to maximum levels the 3rd day after the application of each system. Neither systemic side effects nor adverse metabolic effects were observed except for an increased sensitivity to the platelet aggregating agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1991

Double-blind comparison of perindopril and captopril in hypertension. Effects on left ventricular morphology and function.

Using digitized M-mode echocardiograms, we compared, in a double-blind study, the effects of 4 to 8 mg perindopril given once daily and 25 to 50 mg captopril given twice daily on the left ventricle (LV) in 20 hypertensive patients. Both treatments significantly (P less than .001) lowered blood pressure, reducing systemic vascular resistances. After 3 months both drugs induced a comparable percentage of reduction in LV mass, with an increase in the peak rate of LV relaxation and no changes in the peak rate of LV contraction. Our results demonstrate that perindopril once daily is an effective antihypertensive agent; it is also able, like captopril, to induce regression of LV hypertrophy, with improvement in diastolic performance and no deterioration in ventricular systolic function.

Adult↗
PubMed1990

Metabolic effects of the combination of captopril and hydrochlorothiazide in hypertensive subjects.

The medium-term (16 weeks) effects of the combination of captopril and hydrochlorothiazide (HCTZ) on some metabolic indexes, particularly on plasma lipoproteins, were evaluated in 20 mild to moderate hypertensive outpatients. After a 4-week wash-out period, the subjects were given one tablet of a new commercially available fixed combination once/daily (i.e., captopril 50 mg + HCTZ 25 mg). The dose could be titrated to a maximum of one tablet twice daily according to individual blood pressure responses. Both systolic and diastolic blood pressure significantly decreased at week 4 and showed a further decrease thereafter; the rate of responders (diastolic blood pressure at or below 90 mm Hg at the end of the study) was very high (90%). The only metabolic change was a small though significant increase in HDL cholesterol (P less than .05), almost entirely due to an increase in the denser HDL3 subfraction. The atherogenic fractions, namely total cholesterol, LDL cholesterol, and apoprotein B, showed no significant changes. Plasma triglycerides underwent a transient increase at week 8 (P less than .05) but thereafter fell. Plasma glucose, creatinine, uric acid, and potassium were unchanged. The fixed combination of captopril and HCTZ seems highly effective in lowering blood pressure and seems devoid of untoward metabolic effects. Its overall impact on the coronary risk profile in hypertensive subjects seems therefore to be favorable.

Adult↗
PubMed1987

[Clinical definition of asymptomatic abdominal masses].

Five patients with asymptomatic abdominal masses (abdominal leiomyosarcoma, giant hydronephrosis, renal cell carcinoma, squamous cell carcinoma of the lung metastatic to the adrenal gland, retroperitoneal non-Hodgkin's lymphoma) are reported. Non invasive investigations such as Echography and Computed Tomography, are very advantageous for the quick diagnosis of asymptomatic abdominal masses and for subsequent therapy.

Abdominal Neoplasms↗