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Biomedical subjects

P Giani

Publications and source records attributed to P Giani.

At least 19 recordsLinked to original sources
PubMed1992

Identification of propafenone metaboliser phenotype from plasma and urine excretion data.

The aim of the study was to validate a test based on analyses of urine to identify the propafenone metaboliser phenotype during routine chronic therapy. Twenty seven patients chronically treated with propafenone were studied. A debrisoquine test was performed in 10. Propafenone and its metabolites in plasma and urine were measured by HPLC. Propafenone, 5-hydroxypropafenone and N-depropylpropafenone concentrations in plasma were 1.09, 0.182 and 0.101 ng.ml-1, respectively. Total recovery of the administered dose in urine was 30.7%. Two patients were identified as PM, based on the result of the debrisoquine test (log D/4OHD of 1.26 and 1.36). This finding was confirmed by the propafenone metabolic ratio in urine, but the plasma data did not permit clearcut separation of the phenotypes. Propafenone/5-hydroxypropafenone in plasma was not a good predictor of metabolizer phenotype. Although the number of patients who completed all three tests was limited, it is concluded that analysis of propafenone/5-hydroxypropafenone in urine collected between two consecutive doses at steady-state is more practical than the debrisoquine test and more specific than determining the propafenone/5-hydroxypropafenone ratio in plasma, for identification of the propafenone metaboliser phenotypes.

Adolescent↗
PubMed1992

Washout of long-term treatment with flecainide and propafenone in patients with complex ventricular arrhythmias and cardiac disease. Antiarrhythmic Drug Evaluation Group.

To assess the spontaneous variability of ventricular arrhythmias after withdrawal of apparently successful antiarrhythmic therapy, we enrolled in a washout protocol 40 patients who had completed a randomized controlled 2-year study of antiarrhythmic drugs (the Antiarrhythmic Drug Evaluation Group [ADEG] study). All of them had heart disease and were first seen with high-grade ventricular arrhythmias (Lown class 4a and 4b) at enrollment. After 2 years all of them had responded to propafenone or flecainide; patients who completed the study on a regimen of amiodarone were not considered for the washout study. A total of 27 patients discontinued flecainide and 13 propafenone. Seven days after withdrawal they underwent 24- or 48-hour ECG testing and were classified as true responders (TR) if the arrhythmias were present at the same level as 2 years previously and false responders (FR) if they were below the ADEG responsiveness level. TR patients had a third 24-hour ECG 7 days later, after rechallenge with the same treatment, and FR patients had a third ECG without drugs. Adherence to the protocol was ascertained by measuring drug plasma concentrations at every 24-hour ECG recording. No differences were found in distribution of heart disease and grade of ventricular arrhythmias between patients in the washout study and the remaining group of the ADEG trial. Twenty-four of 40 patients (60%) were true responders. In 4 of the 17 patients who had a third 24 hour ECG, the responsiveness to the same drug was not confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1989

[Cardiomyopathy due to adriamycin: the possibility of its prevention. Monitoring by noninvasive technics].

To prevent delayed cardiomyopathy induced by adriamycin and subsequent severe congestive heart failure, a monitoring schedule with noninvasive techniques to measure cardiac performance (CPK-MB, electrocardiographic, systolic time intervals, echocardiography and quantitative radionuclide angiography) has been used. 15 patients, 33 to 65 years old, with metastatic breast carcinoma, previously treated with a polychemotherapy protocol not including adriamycin have been studied. Monitoring at 0 time allowed to exclude one patient with previous asymptomatic cardiomyopathy and to treat patients at risk with cardiovascular pathology, up to reach and even exceed the dosage of 550 mg/m2. Four of the treated patients showed positive findings of cardiomyopathy at different adriamycin dosage levels: 2 asymptomatic dilatative cardiomyopathies, 1 symptomatic and 1 with congestive heart failure remitted with medical therapy. No patient died because of cardiovascular complications. The results obtained show that of all noninvasive techniques used, only quantitative radionuclide angiocardiography allowed, when employed following an adequate monitoring schedule, to detect reliable findings of moderate and reversible cardiomyopathy thus indicating the appropriate time for drug discontinuation.

Adult↗
PubMed1988

Pharmacokinetics and pharmacodynamics of propafenone during acute and chronic administration.

The pharmacokinetics of propafenone and 5-OH-propafenone and their relationship with the antiarrhythmic action and side effects have been studied in 10 patients with stable, frequent, premature ventricular beats (224-928 premature ventricular complexes/h). Observations were made after a single dose of propafenone 300 mg p.o., and after 1 and 3 months (only 5 out of 10 patients) of therapy with 300 mg t.d.s. After 1 month of treatment the plasma elimination half-life of propafenone (6.7 h) was almost twice as long as after a single dose (3.5 h), and the area under the plasma propafenone concentration-time curve (7620 ng.ml-1.h) was significantly larger than after single dose (3522 ng.ml-1.h); this was also true for the metabolite. The ratio of the AUCs of 5-OH-propafenone and propafenone decreased from the single dose (0.63) to 1 month (0.32). These variables remained stable up to 3 months. Eight patients had greater than or equal to 75% reduction of premature ventricular complexes after 3 days of therapy, and in 7 they were completely suppressed; the response was maintained over 1 to 3 months. Side effects were minor and in no case had the drug to be withdrawn or the dose reduced. Thus, the kinetics of propafenone were time-dependent. Its active metabolite did not accumulate greatly during chronic treatment. The lasting antiarrhythmic effect observed in some patients suggests a b.d.s. regimen instead of t.d.s. dosing in selected patients.

Adult↗
PubMed1987

Reproducibility and reliability of first pass radionuclide ventriculography with Au-195m. Validation of Au-195m radionuclide ventriculography.

Au-195m is a radio-isotope with an ultra-short half-life with which multiple sequential evaluations of ventricular function can be made. In order to evaluate the reliability and reproducibility of analyses of overall and regional ventricular function by radio-isotope ventriculography with Au-195m we studied 10 healthy volunteers and 12 patients with coronary artery disease. Each subject underwent 4 first-pass studies: 1 with Tc-99m and, 10 minutes later, 3 with Au-195m (2 basal studies separated by 3-5 minutes interval and, 10 minutes later, 1 after s.l. nitroglycerin administration). Regional wall motion was analyzed and ejection fraction and peak count rate were determined in each test. Our study showed that the ejection fraction obtained with Au-195m was reproducible (r = 0.98) and correlated well with the ejection fraction determined by using Tc-99m (r = 0.98). The values of the peak count rate obtained with Tc-99m were higher than those obtained with Au-195m. Due to the specially designed collimator and the technical characteristics of the gamma-camera we used, we were able to record sufficiently high count-rates to evaluate regional wall motion, and this analysis was also found to be reliable and reproducible. After s.l. nitroglycerin administration, normal volunteers showed a significant increase of ejection fraction in comparison with basal acquisitions (p less than 0.05), while a wide range of responses was observed in the group of patients with coronary artery disease. We conclude that radio-isotope ventriculography with Au-195m is reliable and reproducible and could be a valid method of monitoring rapid variations induced in overall and regional left ventricular function.

Adult↗
PubMed1986

Evidence for an inhibition of thyroid hormone effects during chronic treatment with amiodarone.

The effects of chronic amiodarone treatment on several thyroid and cardiac function parameters were studied in 50 euthyroid patients with refractory ventricular arrhythmias, divided in responders and nonresponders according to their sensitivity to the antiarrhythmic action of the drug. No differences in the severity of cardiac disease and blood amiodarone concentrations were found in the two groups. Amiodarone induced a significant inhibition of peripheral T4 monodeiodination, more pronounced in responders compared to nonresponders. On the contrary, only in responsive patients, elevated basal and TRH-stimulated TSH levels were observed (despite serum T3 levels were not different from those in nonresponders) and the indirect indices of cardiac performance, particularly the systolic time intervals, fell in a range usually observed in the hypothyroid states. These findings suggest that amiodarone, besides the well-known inhibition of T4 to T3 conversion, also induces a partial resistance to the thyroid hormones, which is probably involved in the therapeutical effectiveness of the drug.

Adolescent↗
PubMed1984

Side effects during therapy with low dosage amiodarone.

Amiodarone is a very active antiarrhythmic agent, but true incidence of Amiodarone-related side effects is still questionable. In a prospective trial of 400 or 200 mg of Amiodarone day for 56 days in 58 patients, we monitored thyroid and liver function, blood count, chest x-ray, ecg. In addiction we took regularly notice of subjective disturbances and physical signs. Side effects were: conduction disturbances 6%, bradycardia less than 50/min. 2%, gastrointestinal 12%, sleep disorders 12%, hyperthyroidism 4,15% and hypothyroidism 6.25%. Blood levels of Amiodarone and desethylamiodarone were not predictive of side effects. Noteworthy was the absence of cutaneous and pulmonary side effects. On the other hand, thyroid function should be monitored carefully because disfunction is not rare (10.4%) and in the case of hyperthyroidism could be related to worsening of arrhythmias.

Adolescent↗
PubMed1984

Blood levels and electrophysiological effects of intravenous amiodarone in patients with junctional reciprocating tachycardia. Preliminary observations.

The time course and the mode of antiarrhythmic action of Amiodarone was studied after acute i.v. injection of the drug (5 mg/kg in 5 min) to four patients with junctional reciprocating tachycardia. Electrophysiological studies were performed before and 1 and 2 hours after Amiodarone injection. It was impossible or considerably more difficult to induce junctional reciprocating tachycardia after Amiodarone, and the drug's effect was detectable mainly on the AV node. Kinetic analysis of blood levels of Amiodarone during the electrophysiological study did not support a direct association between blood concentration and its effects.

Adult↗
PubMed1975

Latent myocardial contractile impairment in patients with angina pectoris.

Intravenous injection of Angiotensin II gives rise to a rapid and transient increase of the afterload of the left ventricle (increased peripheral resistances). In this haemodynamic setting the functional behaviour of the left ventricle, through indirect parameters such as systolic time intervals, was compared in 14 patients with angina and in 15 normal control subjects. As regards blood pressure and heart rate a similar behaviour was registered in the two groups in basal conditions; directly after the intravenous injection of Angiotensin II changes suggesting impairment of left ventricular function failure have been obsered in patients with angina pectoris.

Adolescent↗