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Biomedical subjects

G Cocco

Publications and source records attributed to G Cocco.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effects of a new metabolic modulator, ranolazine, on exercise tolerance in angina pectoris patients treated with beta-blocker or diltiazem.

Ranolazine (RS 43285) is a new piperazine derivative with anti-ischemic properties attributed to a modulation of myocardial metabolism. Its antianginal action was assessed in 104 patients recruited in a double-blind, crossover, randomized study comparing placebo with a single dose of ranolazine (10, 60, 120, and 240 mg). All patients had chronic stable angina pectoris and remained symptomatic (at least 0.1 mV ST-segment depression and angina during prestudy exercise testing) despite treatment with a beta-blocker or with diltiazem. No significant effects of ranolazine on exercise duration or time to angina were observed after the dose of 10, 60, and 120 mg. After the 240 mg dose, however, significant improvement in exercise duration (+13.1% in the combined group, two-tailed p = 0.002; +14.3% in the beta-blocker group, p = 0.009; +11.9% in the diltiazem group, p = 0.06), in time to angina (+56.8 s, p = 0.008), and in time to 1 mm ST-segment depression was observed. The cumulative proportion of patients who improved their time to angina by at least 30 s above placebo were 25, 42, 50, and 72% with the doses of 10, 60, 120, and 240 mg, respectively. Sixty-seven percent of the patients with ranolazine plasma levels above 500 ng/ml improved their time to angina against 40% at plasma levels below 500 ng/ml and summed ST-segment depression during exercise and recovery was also significantly reduced at these plasma concentrations. Both heart rate and arterial pressure at rest and at peak exercise were unchanged after ranolazine, 240 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetanilides↗
PubMed1991

Different hemodynamic (24-h ambulatory blood pressure monitoring) and renin-inhibiting effect of a 1-week treatment with enalapril and lisinopril.

Ambulatory blood pressure and heart rate monitoring were used for comparing the antihypertensive effect of a 1-week treatment with enalapril and lisinopril 10 mg once daily (double-blind crossover placebo-controlled study). Twelve outpatients with mild to moderate hypertension were treated. Both drugs had a significant and identical hypotensive effect. Neither drug affected the diurnal rhythm of blood pressure or heart rate. Therefore the two drugs are equipotent antihypertensive agents. Both drugs inhibited ACE activity to a highly significant extent, but in this regard lisinopril was more effective than enalapril. However, lisinopril's greater ACE inhibition was not accompanied by a greater hypotensive effect. The clinical value of this difference is not yet established.

Adult↗
PubMed1991

A double-blind dose-response study of amlodipine in patients with stable angina pectoris.

Sixty patients (31 male, 29 female) were studied in a 4-week double-blind parallel dose-response study. Patients received amlodipine 1.25 mg (n = 12), 2.5 mg (n = 12), 5 mg (n = 12), 10 mg (n = 12) or placebo (n = 12) once a day. Anti-anginal efficacy was assessed by sequential treadmill testing 24 h post-dose, frequency of anginal attacks and consumption of nitroglycerin, patient and investigator assessment. In the analysis of the final vs baseline total exercise time, the difference between those on amlodipine and those on placebo was significant (P less than 0.01), (all doses). Mean total exercise time increased by 24% in the amlodipine 10 mg group compared with a 20% decrease in the placebo group. The time to onset of angina increased by 37% in the amlodipine 10 mg group, compared with a 16.5% decrease in the placebo group. Differences were statistically significant for the 1.25, 5 and 10 mg amlodipine groups vs placebo. ST-segment charges and rate-pressure product were not affected significantly. There was a statistically significant difference in angina attack frequency and nitroglycerin tablet consumption (P less than 0.05) for all dose groups vs placebo. The majority of patients receiving amlodipine reported improvement in angina symptoms. Side-effects were frequent but mild and dose-related. Amlodipine has significant anti-anginal efficacy. The mechanisms underlying the anti-ischaemic effects of amlodipine are still under discussion.

Administration, Oral↗
PubMed1991

A double-blind, placebo-controlled, parallel dose-response study of amlodipine in stable exertional angina pectoris.

A placebo-controlled, double-blind, dose-response study of amlodipine (1.25, 2.5, 5, and 10 mg once daily) was carried out in 136 patients with stable exertional angina pectoris. Improvements in total exercise tolerance, time to onset of angina during exercise, ST-segment deviation at maximum common load, frequency of angina attacks, and nitroglycerin consumption were greater following amlodipine than placebo. The maximum improvement in exercise parameters occurred with the highest dose of amlodipine. All doses produced significant reductions in angina attack frequency and the rate of nitroglycerin consumption. Amlodipine was well tolerated and no patients were withdrawn due to adverse events or laboratory abnormalities.

Adult↗
PubMed1991

A 6-week double-blind comparison of amlodipine and placebo in patients with stable exertional angina pectoris receiving concomitant beta-blocker therapy.

This study was a multicenter, double-blind comparison of the antianginal efficacy and safety of amlodipine and placebo as adjunctive therapy with constant recommended maintenance doses of beta-blockers. Patients with stable exertional angina pectoris were randomized to placebo or amlodipine at a starting dose of 5 mg once daily. The amlodipine dose was adjusted to 10 mg daily after 2 weeks if angina attacks were not abolished. Antianginal efficacy was assessed throughout the study with angina diaries, investigators' and patients' global evaluations, and with bicycle exercise tests during a placebo run-in period (baseline) and after 2 and 6 weeks of double-blind treatment. On baseline-final analysis, the exercise time to angina onset increased by 13% with amlodipine compared to 6% with placebo (p < 0.05). The total exercise time increased by 11% on amlodipine compared with 2% on placebo, though this difference did not reach statistical significance. Angina attack frequency and nitroglycerin consumption were both reduced by adding amlodipine to beta-blocker treatment. Amlodipine in combination with beta-blocker therapy was well tolerated, with a low incidence of side effects and laboratory test abnormalities. The study showed clearly that addition of amlodipine to beta-blocker therapy in patients with stable angina pectoris was well tolerated and gave improved antianginal efficacy.

Adolescent↗
PubMed1991

Aspirin-induced asthma and bronchial hyperresponsiveness.

The inhalation challenge with lysine-aspirin (L-ASA) using the dosimeter method allows the construction of a dose-response curve and the quantitative estimation of airway responsiveness to the drug. We assessed the modifications of airway responsiveness to methacholine in four groups of subjects: aspirin-sensitive asthmatics, aspirin-sensitive subjects with urticaria/angioedema, subjects with an equivocal history of aspirin intolerance and normal control subjects. The L-ASA challenge was positive in all aspirin-sensitive asthmatics. The pattern of bronchial response to the challenge was different from that observed after challenge with allergens or occupational sensitizers. The main difference was found in the recovery from induced bronchoconstriction. The recovery lasted from 3 to 6-8 hours, and a peculiar dose-response curve was obtained that we call "early prolonged reaction". In five of 18 ASA-sensitive subjects there was a significant increase in airway responsiveness. Airway responsiveness was normal in aspirin-sensitive nonasthmatic subjects and in the other two groups studied. We conclude that L-ASA inhalation challenge may increase bronchial hyperresponsiveness in some ASA-sensitive asthmatics. This presence of enhanced bronchial hyperesponsiveness seems to be a marker with which to distinguish ASA-sensitive asthmatics from ASA-sensitive subjects with urticaria/angioedema.

Adolescent↗
PubMed1991

The N-nitrosoproline test as a measure of cancer risk in geographical comparison studies: results from Italy and an overall comparison.

The N-nitrosoproline (NPRO) test has been used in studies in which populations at high risk of cancer have been compared with equivalent populations at lower risk, to examine whether the geographical variation in cancer risk correlates with propensity for endogenous nitrosation, as assessed by the NPRO test. The usual method employed has been to determine NPRO in 12- or 24-h urine samples, after ingestion of L-proline, in a representative sample of the general population. We present results from one such geographical study conducted in two regions of Italy (Florence and Cagliari) with an approximately three-fold variation in gastric cancer mortality. The nonsignificant difference in mean NPRO excretion between the two populations was insufficient to explain the difference in cancer risk. The fact that there are appreciable international differences in formation of NPRO suggests, firstly, that nitrosation may be of relevance to cancer risk in some countries but not in others and, secondly, that variations within one country may not be large enough for significant geographical differences to be evident. Multivariate analysis of individual, rather than grouped, results from our Italian study made it possible to quantify the relevance of different factors to NPRO formation: a major factor is exposure to nitrate. Important relationships may be missed by analysing only grouped data.

Humans↗
PubMed1990

[Autotransfusion in vascular surgery].

This report describes 51 vascular patients with peripheral vascular disease treated intraoperatively by means of the autotransfusion apparatus with a minimum of 750 cc of reinfused blood. An early decrease of Hct, Hb, RBC, fibrinogen and Plt count was observed without any significant coagulation disorder.

Aged↗
PubMed1989

Intrasubject between-day variability of PD20 methacholine assessed by the dosimeter inhalation test.

The intrasubject between-day variability of the methacholine inhalation test (MIT) was estimated in a group of 30 patients (15 males, mean age 29 yr), representative of a wide range of degrees of nonspecific bronchial responsiveness (from normal to severely increased). In each patient, an MIT with the dosimeter method was carried out on three separate occasions within one week, keeping as constant as possible both the technical and patient-related factors (FEV1 within +/- 5 percent, no recent airway inflammation) and independently from operator-related factors (three tests, three different operators blinded with regard to previous MIT results). On each occasion, twofold increasing doses of methacholine were given from 6.25 to 3,200 micrograms as cumulative doses, at five-minute intervals by means of a dosimeter Me.far MB3 (nebulization time 0.8 +/- 0.2s, output 5 +/- 0.2 microliters/puff). The FEV1 was measured initially and 1.5 and 3 minutes after each inhalation. The test was continued until either a fall of 20 percent or more in FEV1 was obtained or the last dose was reached. The results were expressed in terms of PD20, ie, the dose of methacholine producing a 20 percent fall in FEV1. Under these carefully controlled conditions, the 95 percent confidence intervals (as based on a single determination) corresponded to +/- 0.22 on a log10 scale or, in a more meaningful way, +/- 1.66 fold-difference in PD20 from one visit to the other.

Adolescent↗
PubMed1988

Ergometric evaluation of the effects of enalapril maleate in normotensive patients with stable angina.

The anti-ischemic effect of a single oral dose of 10 mg of enalapril maleate (E) was investigated in 14 normotensive patients with coronary artery disease (CAD) and stable effort-induced angina pectoris. An exercise stress test was performed three times in each patient at the same clock hour on three successive days: with no treatment (baseline), 6 h after administration of placebo (P), and 6 h after oral administration of a single 10 mg dose of E. The multistage nonstop effort tests were performed in the sitting position. Workload started at 25 W and was increased by 25 W every 2 min until an ischemic ST depression of more than 1.5 mm was observed. The following parameters were measured: heart rate (HR), systolic blood pressure (BP), rate-pressure product (RPP), workload sustained (WS), elapsed time of effort (ET), and millimeters of ischemic ST depression. The values of the parameters observed with baseline, P, and E were compared at the moment of appearance of chest pain or ischemic ST depression, at the moment of maximal effort, maximal common WS (MCWS), and maximal common RPP (MCRPP). Enalapril delayed the appearance of the ischemic ST depression. At the MCWS, the RPP was significantly lower under E and the ST depression was less marked; this effect was the result of a lower BP level, in the absence of any significant change in HR response. The acute effects of E observed in normotensive patients with effort-induced angina pectoris seems to be related to the inhibition of angiotensin at the coronary level and to its antiadrenergic action.

Angina Pectoris↗
PubMed1988

Dose-titration study of alfuzosin, a new alpha 1-adrenoceptor blocker, in essential hypertension.

An open, dose-titration study of alfuzosin, a new selective post-synaptic alpha 1-adrenoceptor antagonist with additional direct vasodilator properties has been performed. After a 3-week run-in placebo period, 12 patients with essential hypertension received alfuzosin 5 mg oral b.d., and then the dose was doubled every week, up to a maximum of 20 mg q.i.d. if the supine diastolic blood pressure was greater than 90 mm Hg. The study lasted for 4 weeks. Supine blood pressure (SBP) decreased from 160/102 (Day 0) to 148/89 mm Hg and upright blood pressure (UBP) from 151/102 (Day 0) to 137/84 mm Hg. Alfuzosin did not cause any significant change in supine or upright heart rate. In addition, after the first dose of alfuzosin, supine and upright blood pressure and heart rate (SHR and UHR) were measured every 30 min for 5 h. The fall in blood pressure was significant after 90 min and it lasted up to the 5th hour; the maximum effect was observed after 3 h: SBP decreased from 159/103 (time 0) to 137/84 mm Hg and UBP from 150/102 (time 0) to 123/79 mm Hg. SHR was increased from 72 (time 0) to 81 beats/min at the 5th hour and UHR from 87 to 101 beats/min at the 4th hour. A weak but significant correlation was observed between the hypotensive effect 12 h after drug intake and the plasma concentration of the drug at that time. A 10% decrease in supine diastolic blood pressure was found at a drug plasma concentration higher than 7 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1988

Multicenter placebo-controlled comparison of amlodipine and atenolol in mild to moderate hypertension.

Once-daily administration of amlodipine, a long-acting dihydropyridine calcium-channel blocker, and atenolol, a cardioselective beta-adrenoceptor blocking agent, were compared in patients with mild to moderate hypertension in a multicenter placebo-controlled trial. The starting dose of amlodipine was 2.5 mg, with upward adjustment to 5.0 mg and 10.0 mg at 2-weekly intervals; atenolol was started at 50 mg and titrated to 100 mg after 4 weeks. After 8 weeks of treatment, amlodipine and atenolol both reduced blood pressure to a statistically and clinically significant extent at 24 h postdose, and with a small trough-peak (i.e., 24 h to 8 h postdose) difference. Unlike atenolol, amlodipine had no effects on heart rate. The incidence of side effects was low. There were no clinically significant changes in serum lipids with either drug. It is concluded that once-daily dosing with either amlodipine or atenolol significantly reduces blood pressures. Both amlodipine and atenolol were well tolerated.

Adult↗
PubMed1987

Magnesium depletion in patients on long-term chlorthalidone therapy for essential hypertension.

Sixty patients were treated for 1 year for essential uncomplicated hypertension, 30 with beta-blockers alone (BB) and 30 with BB and chlorthalidone (CTD). BB did not affect serum K+ or Mg++. In the BB-group there was a statistically significant trend towards retention of Mg++ in a loading test, but the effect was clinically marginal. BB + CTD reduced serum K+ and Mg++ and caused significant Mg++ depletion, as shown by the Mg++ loading test. All the effects were highly significant and were clinically important. The metabolic perturbations due to CTD are potentially dangerous and make this drug unattractive as 'first choice' treatment for hypertension.

Adrenergic beta-Antagonists↗
PubMed1987

Effects of captopril on the physical work capacity of normotensive patients with stable-effort angina pectoris.

Twelve normotensive patients with coronary artery disease and stable effort-induced angina pectoris were selected: the antiischemic effect of captopril was studied. A maximal cycloergometer effort test was obtained before (base) and after administration of placebo or captopril (50 mg p.o.). The following parameters were measured: heart rate (HR), blood pressure (BP), maximal rate/pressure product (MRPP), maximal workload sustained, (MWS), maximal working time (MWT), and S-T depression at MRPP. The base and placebo were similar. Compared to them captopril augmented the MWT, increased the MWS, reduced S-T depression at MRPP, and decreased the number of patients with effort-induced angina pectoris. The antiischemic effect of captopril seems related both to its effect on HR and BP, and to a local enhancement of coronary blood flow.

Angina Pectoris↗