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Biomedical subjects

G Perani

Publications and source records attributed to G Perani.

At least 19 recordsLinked to original sources

[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

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

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

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

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

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

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

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

[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

Increase in plasma HDL-cholesterol in hypertensive patients treated with enalapril.

The effects of enalapril on plasma lipoproteins were evaluated in an open study of 12 normolipidemic outpatients with mild-to-moderate essential hypertension (World Health Organization stages I and II). After a two-week washout period, during which placebo was given, the patients received 20 to 40 mg/day of enalapril for 16 weeks. Treatment with enalapril was associated with significant increases in levels of HDL cholesterol (mean, 23%; P less than 0.001) and apoprotein A (mean, 11%; P less than 0.01), largely because of the increase in the subfraction HDL2 (mean, 43%; P less than 0.001), although the subfraction HDL3 also rose (mean, 14%; P less than 0.005). Total cholesterol and LDL cholesterol levels did not change, whereas triglycerides decreased significantly (mean, 26%; P less than 0.001). Apoprotein B was unchanged. Unlike diuretics and most beta-blockers, enalapril favorably affects plasma lipoprotein levels, thus improving the overall cardiovascular risk in hypertensive patients.

Adult

Effect of mepindolol on serum lipids.

In view of the postulated association between plasma lipids and the development of atherosclerosis, there is growing interest in the effects of beta blockers on plasma lipids. This study was undertaken to investigate whether a nonselective beta blocker, such as mepindolol, which possesses intrinsic sympathomimetic activity, causes significant changes in serum lipids, particularly in their ditribution among the different lipoproteins. Eighteen healthy subjects, twelve males and six females, were given mepindolol orally, daily doses of 0.2 mg/kg averaging 10-15 mg. Pre- and post-treatment fasting total serum cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were evaulated; the ratio LDL cholesterol/HDL cholesterol was also calculated. Total cholesterol did not change significantly after treatment with mepindolol (- 1.9 mg%), whereas a small and nonsignificant decrease was observed in LDL cholesterol (- 6 mg%); no change was found in HDL cholesterol (- 0. mg%). Serum triglycerides showed a significant increase (+ 20.9 mg%, p less than 0.01). Thus, the most prominent effect of even a short period of treatment with mepindolol is a net increase in serum triglyceride levels. It must be remembered that high triglyceride levels do not constitute a cardiovascular risk factor. On the other hand, no significant changes in total cholesterol, HDL and LDL cholesterol, and in LDL cholesterol/HDL cholesterol ratio were observed. The results of this study show that mepindolol, unlike other beta-blocking agents, does not affect cholesterol concentration and distribution among the lipoproteins. In particular it does not reduce HDL cholesterol, which is currently assumed to be inversely related to the development of atherosclerosis.

Adult