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Biomedical subjects

M Motolese

Publications and source records attributed to M Motolese.

At least 19 recordsLinked to original sources
PubMed1992

Effect of cigarette smoking and of a transdermal nicotine delivery system on glucoregulation in type 2 diabetes mellitus.

The effect of nicotine absorbed transdermally from a patch (TNS) and from cigarette smoking on insulin secretion and action in Type 2 diabetes has been compared. Twelve Type 2 diabetic smoking patients, aged 51 y, with diabetes for 9 y, treated either with diet and/or oral hypoglycaemic agents, were studied on three occasions, according to a double-blind, placebo-controlled, cross-over design. The subjects were investigated 12 h after their last cigarette or application of one patch of TNS 30 cm2 or TNS placebo, or whilst smoking their usual cigarette. Insulin secretion was assessed by a glucagon (1 mg IV) stimulation test. On a second occasion, insulin action was assessed by a hyperglycaemic-hyperinsulinaemic clamp, the spontaneous hyperglycaemia of the fasting state (8.61 mmol.l-1) being maintained during a 4 h insulin infusion (at 0.1 mU.kg-1.min-1 for the initial 2 h, and 1 mU.kg-1.min-1 during the last 2 h). TNS and the cigarette did not affect endogenous insulin secretion as compared to placebo. During the initial 2 h of the clamp study, plasma insulin increased from 88 to 155 pmol.l-1, hepatic glucose production (3-3H-glucose) was less suppressed after TNS (4.31 mumol.kg-1.min-1) than after placebo (2.5 mumol.kg-1.min-1), but was more suppressed than after cigarette smoking (5.61 mumol.kg-1.min-1). In the last 2 h of the clamp (plasma insulin 646 pmol.l-1), glucose utilization was less stimulated after TNS (36.1 mumol.kg-1.min-1) vs placebo (39.8 mumol.kg-1.min-1), but more than after cigarette smoking (33.6 mumol.kg-1.min-1), primarily because of a decrease in glucose storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1991

Comparison of left ventricular ejection fraction by magnetic resonance imaging and radionuclide ventriculography in idiopathic dilated cardiomyopathy.

To assess the validity of gated magnetic resonance imaging (MRI) in determining left ventricular (LV) ejection fraction (EF), MRI (Spin Echo, multislice-multiphase technique on the short-axis plane) was compared with equilibrium radionuclide ventriculography in 32 patients with idiopathic dilated cardiomyopathy. All patients underwent MRI and radionuclide ventriculography, performed consecutively on the same day (mean time interval between the 2 examinations: 40 minutes). Comparison with LVEF showed a high correlation (y = 0.79 X +3.51, r = 0.91; p less than 0.001). Mean difference between radionuclide ventriculography and MRI data was 1.7, with the 95% confidence interval 0.71 to 2.68: MRI slightly underestimated LVEF. MRI interobserver and intrapatient variability (assessed in 15 of 32 patients) showed a high correlation (r = 0.91, r = 0.98). In conclusion, data suggest that MRI, using the short-axis approach and the multislice-multiphase technique, is an accurate, noninvasive, highly reproducible method of evaluating LVEF in patients with idiopathic dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed1991

Pharmacokinetics of cadralazine in a large group of hypertensive patients chronically treated with cadralazine: advantage over a conventional study in a small group of patients.

The concentrations of cadralazine in plasma were studied in 101 hypertensive patients treated with oral doses of 10, 15, or 20 mg of cadralazine once daily. Most of the patients received additionally a beta-blocking drug (n = 87) and a diuretic (n = 52). Few blood samples were collected in each patient on several occasions during the treatment, which usually lasted for more than 6 months. No accumulation of cadralazine in plasma occurred in any of the patients and the maximum concentrations were similar to those recorded in a small sample of healthy volunteers. The terminal half-life of elimination (3.6 h) was longer than that observed in healthy subjects (approximately 2.5 h). Conversely, the total clearance (197 ml/min) was lower (285 ml/min in healthy). The half-life and the total clearance in plasma were not dose dependent. In the patients treated for more than 6 months, no change in the pharmacokinetics of cadralazine was detected. The description of the distribution of concentrations showed that one-half of the patients behaved similarly to healthy subjects concerning half-life and total clearance. The other half presented a slower elimination of the drug (t 1/2 = 4.4 h and ClT = 130 ml/min) and these patients were significantly older (p = 0.01) than the former. This suggests that special attention should be paid to old hypertensive patients when a dose higher than 15 mg once daily is prescribed. Though concentrations were proportional to the dose, the body weight was not found to be a determining factor for dose adjustment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Long-term effects of benazepril on ambulatory blood pressure, left ventricular mass, diastolic filling and aortic flow in essential hypertension.

We investigated the long-term effects of benazepril, a new non-sulfydryl angiotensin converting enzyme inhibitor, on ambulatory blood pressure (BP) and left ventricular (LV) anatomy and function in 13 never treated hypertensive patients (mean age 55 years--SD 9). Non-invasive ambulatory BP monitoring (Spacelabs 90202, a reading every 15 min for 24 hours) and standard and pulsed Doppler echocardiography were performed basally and after 12 months of therapy. Echocardiography was performed also at the end of 18th month of treatment. Eleven patients required a single daily dose of benazepril 10 (n = 9) or 20 (n = 2) mg, and two patients of 20 mg plus chlorthalidone 25 mg, to achieve clinical BP control. Average 24 h systolic/diastolic BP was 156/100 mmHg (SD 17/5) basally and 144/90 mmHg (SD 16/7) at the end of the 12th month of treatment (all p less than 0.01), LV mass index was 133 g/m2 basally and 113 g/m2 at the 12th month (p less than 0.01), early transmitral flow velocity (peak E) was 0.43 m/s (SD 0.11) basally and 0.62 (SD 0.13) m/s at the 12th month (p less than 0.01), and late transmitral flow velocity (peak A) did not change [0.67 (SD 0.10) m/s basally and 0.64 (SD 0.11) m/s at the 12th month]. Peak A/peak E ratio decreased from 1.69 (SD 0.57) to 1.31 (SD 0.37) (p less than 0.01). Peak aortic velocity, aortic acceleration time and aortic acceleration did not change. The per cent reduction of LV mass index was more closely related to the reduction of average 24 h systolic (r = 0.66, p = 0.013) and diastolic (r = 0.72, p = 0.005) BP than to the reduction of casual systolic (r = 0.37, p = NS) and diastolic (r = 0.42, p = NS) BP. None of the echocardiographic indices changed between the 12th and 18th month of treatment. In a control group of 13 age- and sex-matched healthy normotensive volunteers who underwent 24 h ambulatory BP monitoring and echocardiography twice, 12 months apart, there were no statistically significant BP or echographic changes. In summary, long-term antihypertensive treatment with benazepril provided and effective 24 h BP control, associated with regression of LV hypertrophy and improvement in LV diastolic filling, without changes in LV systolic function.

Ambulatory Care↗
PubMed1991

A comparison of metoprolol OROS with antenolol in the treatment of effort angina pectoris: a randomized double-blind study.

The antianginal efficacy of metoprolol OROS has been investigated in comparison with that of atenolol in a multicenter double-blind cross-over trial carried out in patients with stable effort angina. OROS (ORally OSmotic) is a new semi-permeable delivery system with very slow osmotic release of the active drug, which is maintained at virtually constant plasma levels throughout the 24 hours. At the end of a 2-week run-in period, 53 patients with chronic coronary artery disease and documented ischemia during bicycleergometric exercise test were given, on double-blind condition, metoprolol OROS 21/285 and atenolol 100 mg in random order for 4 weeks each. On the last day of each cross-over period, patients underwent a bicycleergometric exercise test 24 hours after the last drug intake. The mean number of anginal attacks (2.54 during the 2-week run-in period) decreased under both metoprolol OROS (1.29 and 1.13 after 2 and 4 weeks of treatment, respectively) and atenolol (1.29 and 0.73 after 2 and 4 weeks of treatment, respectively), with no difference between the two beta-blockers. The same behaviour was observed as regards the nitroglycerin tablets consumption. The exercise test variables (i.e. duration of exercise, maximum workload and peak exercise values of systolic and diastolic blood pressure, heart rate and ST-segment depression) did not differ between the two treatments and did not show a time-effect. The percentage of patients reporting adverse effects was low with both treatments. Two patients were withdrawn from the study during atenolol (gastralgia and heartburn, respectively), and one during metoprolol OROS (gastralgia).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Comparative evaluation of cardioselectivity of metoprolol OROS and atenolol: a double-blind, placebo-controlled crossover study.

Cardioselectivity of a single oral dose of metoprolol oral osmotic (OROS) (14/190 mg) and atenolol (100 mg) was compared in 12 patients with reversible obstructive airway disease by assessing the dose-response curve to increasing doses of inhaled salbutamol. The beta-blocking activity of the two drugs, which was determined by measuring heart rate, blood pressure, and derived indexes at peak plasma drug levels, was similar. Both metoprolol and atenolol significantly reduced forced vital capacity and peak expiratory flow, with no difference between drugs. Atenolol but not metoprolol also significantly reduced forced expiratory volume in 1 second and specific airway conductance. Both metoprolol and atenolol shifted the dose-response curve of specific airway conductance to the right. The results indicate that the new OROS delivery system for metoprolol, which produces a relatively constant plasma drug level, provides a cardioselectivity comparable to or greater than that of atenolol at maximum plasma levels.

Adolescent↗
PubMed1990

Transient myocardial ischaemia: a multivariate analysis on clinical, angiographic and ergometric variables.

The availability of ambulatory ECG monitoring allows identification of transient myocardial ischaemia, the clinical relevance of which is currently being investigated. Ninety-four consecutive patients with ischaemic heart disease and a positive exercise test (greater than or equal to 1 mm ST-segment depression) were studied to evaluate the prevalence of transient myocardial ischaemia (either painless or painful) during 24-h dynamic electrocardiogram (ECG) and the clinical, angiographic and ergometric variables predicting its appearance. Two-hundred-and-eighty-one episodes of transient electocardiographic myocardial ischaemia were recorded in 69 patients (73.4% of all patients). Transient myocardial ischaemia was more frequent, although not significantly so, in patients with diabetes, with previous myocardial infarction, or with multivessel disease. When tested by multivariate analysis, neither the clinical variables nor the severity of coronary artery disease allowed prediction of the occurrence of transient myocardial ischaemia during dynamic ECG. The duration of exercise testing up to the ischaemic threshold (ST-segment depression = 1 mm) and the peak heart rate during exercise were more accurate predictors of transient myocardial ischaemia (P = 0.019 and 0.012 respectively). Patients with transient myocardial ischaemia had a lower ischaemic threshold (355 +/- 175 vs 498 +/- 150 s, mean +/- SD, P = 0.001) despite a lower peak heart rate (129 +/- 18 vs 137 +/- 12 beats min-1, P = 0.047) than patients without transient myocardial ischaemia. In conclusion, exercise testing may help select patients for examination by dynamic ECG.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography↗
PubMed1989

Blunting of atrial natriuretic factor response to volume expansion by benazepril in hypertensive patients.

To verify the hypothesis that the angiotensin converting enzyme (ACE) level may affect the metabolism of circulating atrial natriuretic factor (ANF), the acute and chronic effects of benazepril on plasma ANF levels were studied in hypertensive patients under basal conditions and in response to acute volume expansion. Ten essential hypertensives entered a double-blind crossover study, and were randomly allocated either to placebo or to 10 mg benazepril orally once a day for 2 days; after a placebo washout period of 2 days the groups were crossed over. On the second day of each crossover period, volume expansion was induced by infusing 1 litre saline in 30 min, and blood samples for ANF measurements were drawn at times -5, 0, 5, 15, 30, 35, 40, 50 and 60 min. Oral benazepril at 10 mg/day was then given to all patients for 4 weeks, and the volume expansion with saline was repeated. After the 2-day acute benazepril treatment, blood pressure fell from 166.1 +/- 3.6/105.1 +/- 0.9 to 140.1 +/- 4.6/85.6 +/- 2.1 mmHg (P less than 0.01 for both systolic and diastolic blood pressure), whereas ANF fell from 29.4 +/- 3.6 to 24.1 +/- 3.7 pg/ml (NS) after the acute benazepril treatment and to 17.7 +/- 3.6 pg/ml (P less than 0.01) after the chronic benazepril treatment. The volume expansion itself did not induce significant changes in mean arterial pressure, either during the placebo treatment or during the acute chronic benazepril treatment. The rise in ANF values in response to saline infusion during placebo was prompt, beginning at min 15 and reaching a maximum at min 40.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Regional and systemic hemodynamic and humoral effects of transdermal nitroglycerin in mild hypertension.

Venous distensibility, forearm blood flow (FBF, plethysmographic technique), systemic blood pressure (BP), and derived forearm vascular resistances were measured in 11 borderline-mild hypertensive, otherwise healthy male subjects for a 24-h period during either placebo or transdermally delivered nitroglycerin (NTG 10 mg/24 h). The drug caused arteriolar and venular forearm vasodilation and hypotension which, although persisting throughout the 24-h observation period, reached an apparent maximum during the first hours but later tended to wane. Since NTG plasma levels were constant at that time, the data may suggest development of vascular hyporesponsiveness during continuous exposure to NTG. Venous hematocrit (Hct) decreased during transdermal NTG, indicating the plasma volume expanding action of the drug, apparently dissociated from vasodilation per se. Because no significant changes in either plasma norepinephrine (NE) or plasma renin activity occurred in these subjects, counterregulatory sympathetic or angiotensin II (AII)-mediated vasoconstriction was probably not involved in the hemodynamic action of transdermally delivered NTG.

Administration, Cutaneous↗
PubMed1987

Antihypertensive effect of a new formulation of slow release oxprenolol in essential hypertension.

To test whether a new formulation of a slow release oxprenolol (SLOx) can produce a steady 24-h antihypertensive effect, we recorded 24-h intraarterial blood pressure (Oxford technique) in eight ambulant inpatients (age 44.5 +/- 3.0 years, mean +/- SE) with a mild or moderate hypertension who were untreated since three weeks. The study was started seven days after hospitalization and was conducted according to a randomized doubleblind cross-over design. Blood pressure recordings were made after (a) a 7-day administration of SLOx in a single evening dose, and (b) a 7-day administration of placebo. This design allowed to determine the effect of SLOx without interference from nonspecific blood pressure lowering factors. Blood pressure effects of handgrip, submaximal cyclette exercise, and cold pressor test 20-24 h after the administration of SLOx and placebo were also evaluated. The blood pressure tracing was analyzed beat-to-beat by a computer which provided also the analysis of the heart rate data. The 24-h mean systolic and diastolic blood pressure measured during placebo were 144.6 +/- 6.4 and 81.1 +/- 3.9 mm Hg, the corresponding heart rate being 76.9 +/- 3.5 beats/min. SLOx reduced these values by 6.2, 10.6, and 4.8%, respectively, all effects being similarly evident throughout the blood pressure recording. The pressor responses to handgrip, cyclette exercise, and cold pressor test were not affected by SLOx. By contrast, the small tachycardic response to handgrip and the large tachycardic response to submaximal cyclette exercise were significantly reduced by the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Antihypertensive activity of a new vasodilator, cadralazine, administered alone or in combination with a beta-blocker.

The antihypertensive activity of a new arterial dilator, cadralazine, was evaluated in 40 patients with mild-to-moderate arterial hypertension. Cadralazine was given once daily over 6 weeks, and blood pressure and heart rate were recorded 24-26 hours after dosing. Cadralazine dose was 10 mg daily initially, and 15 or 20 mg daily from the 3rd or 5th trial week according to a target diastolic pressure reduction to 95 mmHg or below. Slow-release metoprolol 200 mg once daily was added when heart rate increase exceeded 25% of the pretreatment value. Blood pressure showed a significant and progressive reduction throughout the study period, both in the patients receiving cadralazine as monotherapy (19 patients) and in those who added metoprolol (21 patients). The target diastolic pressure reduction was reached in 2 patients with the 10-mg dose, in 19 of the remaining 38 patients with the 15-mg dose, and in 13 of the other 19 patients with the 20-mg dose. Considering only those patients who did not add metoprolol, the target was reached in the 2 patients with the 10-mg dose, in 10 of the 19 patients with the 15-mg dose and in 7 of the 19 patients with the 20-mg dose. None of the laboratory tests showed clinically relevant changes. Neither LE cells nor antinuclear antibodies were found. In conclusion, cadralazine is a promising long-acting antihypertensive vasodilator. A clinically satisfactory antihypertensive effect is achieved mostly by a 15-mg or a 20-mg dose given once daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1979

Antihypertensive effect of oxprenolol and chlorthalidone in fixed combination, given once daily.

In a multicentre, single-blind, within-patient study, the effectiveness and tolerability of the fixed combination oxprenolol 80 mg + chlorthalidone 10 mg per tablet given once daily, compared to the well established b.i.d. schedule, has been investigated in forty out-patients with mild to moderate hypertension. After a two-weeks placebo wash-out, twenty patients were given 1 tablet b.i.d. of the fixed combination for 4 weeks and thereafter 2 tablets once-daily for a further 4 weeks; the remaining twenty patients were given the fixed combination in the reverse order. There was no significant difference in clinical response between the two treatment regimes, which were equally effective and well tolerated. However, patient compliance might be considerably improved with the once-daily dosage schedule of the fixed combination.

Adult↗