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Biomedical subjects

C Libersa

Publications and source records attributed to C Libersa.

At least 55 records · Page 3Linked to original sources

Effect of quinidine on the dextromethorphan O-demethylase activity of microsomal fractions from human liver.

1. The kinetics of dextromethorphan O-demethylation were measured in microsomes prepared from five human livers, both in the absence and in the presence of quinidine. 2. For each liver and over the concentration range of dextromethorphan examined (4.2-3400 microM), this reaction involved an enzymatic component of high affinity, with an apparent Michaelis-Menten constant (Km) of 4.6 +/- 1.8 microM (mean +/- s.d.) and a maximum velocity (Vmax) of 4.2 +/- 3.5 nmol mg-1 h-1 (mean +/- s.d.). 3. Quinidine was a potent and competitive inhibitor of the activity of this component (mean Ki +/- s.d. of 0.025 +/- 0.008 microM) as it is for other oxidation reactions which have already been found to co-segregate with the debrisoquine-type polymorphism. 4. With microsomes from four of the five livers studied, there was evidence of a second enzymatic component of activity characterized by a similar Vmax and about 20-fold higher Km compared with the high affinity component. The activity of this low affinity component was unaffected by quinidine in the concentrations studied.

Chromatography, High Pressure Liquid↗

High-performance liquid chromatographic assay for mexiletine hydroxylation in microsomes of human liver.

A simple high-performance liquid chromatographic assay, using fluorescence detection, is described for determining simultaneously the production of the two major hydroxylated metabolites of mexiletine in human liver microsomes. The detection limits of hydroxymethylmexiletine and p-hydroxymexiletine are 0.35 and 0.08 nmol/ml, respectively. The assay is specific, reproducible and allows the simultaneous kinetic characterization of the reactions in small amounts of liver tissue. The assay may be used to acquire a better knowledge of the kinetic behaviour of mexiletine and of its metabolites, and to investigate if the large inter-individual variations of the mexiletine pharmacokinetics are of metabolic origin, due to variations of its hydroxylation processes.

Chromatography, High Pressure Liquid↗

[Late ventricular potentials. Clinical applications and relation to severe ventricular arrhythmias].

The recording of late ventricular potentials with high amplification cardiography (HAC) permits to identify patients presenting a risk of sudden death and ventricular tachycardia, especially in the later stage of myocardial infarction. Few authors have studied the prevalence of these potentials in other heart diseases presenting a risk of sudden death. Most series in the literature are too small to specify variations in the prevalence of these potentials according to the severity of the coronary disease. For this purpose, 835 patients including 535 coronary patients were evaluated with HAC compared to data from coronary angiography and Holter test. An automatic quantification method of the late potentials was used on 131 healthy subjects. The prevalence of late potentials is 32 p. cent after infarction, and 75 p. cent when a chronic ventricular tachycardia is present. These potentials retain their significance of tracers of ventricular arrhythmias in primary dilated myocardiopathies, with a prevalence of 25 p. cent reaching 50 p. cent in case of ventricular tachycardia. Their recording in the presence of idiopathic ventricular extrasystoles must be an indication to look for an underlying cardiopathy. It is possible to record them in other diseases especially in advanced valvular cardiopathies, as well as in right ventricular dysplasias with arrhythmia where their presence has a great diagnostic value.

Arrhythmias, Cardiac↗

Propafenone versus disopyramide: a double-blind randomized crossover trial in patients presenting chronic ventricular arrhythmias.

In vitro and in vivo electrophysiological studies have shown that propafenone could be classified as a class I antiarrhythmic agent. The aim of this study was to investigate the short-term antiarrhythmic efficacy and safety of propafenone in 10 patients compared to disopyramide in a double-blind randomized protocol. Included patients suffered from ventricular arrhythmias with at least 60 ventricular premature beats (VPB) per hour refractory to at least two other antiarrhythmic agents. At the end of the control period and of the two treatment periods during which patients received either propafenone (300 mg three times a day) or disopyramide (200 mg three times a day), clinical examination, Holter recordings, electrocardiogram, and clinical laboratory tests were performed. The PR interval and the QRS interval were significantly increased with propafenone, but not with disopyramide. The cQT interval was not significantly changed by either propafenone or disopyramide. Heart rate was decreased with propafenone (p less than 0.05) with no change in the diurnal/nocturnal circadian ratio variation. Heart rate was significantly decreased with disopyramide only during the day. Five of nine patients in the propafenone group and two of nine patients in the disopyramide group showed a reduction in ventricular premature beats greater than 80%. Total resolution of severe arrhythmias (repetitive events) was seen in 5 of 8 patients with propafenone; 2 of 8 with disopyramide. Adverse events, when they occurred, were mild (visual disturbances, epigastric discomfort, changes in taste perception, transient atrioventricular block with propafenone, and photophobia with disopyramide), and did not require reduction or discontinuation of study drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Raynaud's phenomenon and finger necrosis after treatment of ovarian seminoma with bleomycin, vinblastine and 5-fluorouracil].

Bleomycin is sometimes at the origin of a Raynaud's phenomenon (RP). From the literature, there does not seem to exist a dose-dependent relationship. The phenomenon occurs early or late and often is resistant to various medications. The possible physiopathological mechanisms are: direct vascular toxicity, hypersensitivity vascularization, alteration of platelets activity, alteration of Willebrand's factor, and as predisposing factors: association to periwinkle alkaloids or hypomagnesemia.

Adult↗

[Prevalence of late potentials in ventricular tachycardias. Comparison with a control group].

High amplification electrocardiographic recording of ventricular late potentials was introduced a few years ago and seems to be a simple, reliable and reproducible method to identify patients at a high risk of sudden death and ventricular tachycardia, principally during the chronic phase of myocardial infarction. However, few authors have studied quantitatively the prevalence of late potentials in patients with ventricular tachycardia compared with a sufficiently large sample of healthy subjects. In this study 34 patients with sustained ventricular tachycardia (11 women, 23 men, mean age 58 years) and 131 healthy subjects (29 women, 102 men, mean age 29 years) underwent high amplification time-averaged ECG recording, and an algorithmic analysis of the tracings was conducted, using the Simson method. Three numeric parameters were used in the interpretation of the tracings: HFRMSA = mean RMS amplitude of the last 40 milliseconds of QRS; HFD40 = delay in signal decrease from amplitude 40 mu v to baseline, and delta QRS = difference in QRS duration with 0-250 Hz and 25-250 Hz filterings. Normal values, as determined from measurements in healthy subjects, were: HFRMSA above 27 mu v, HFD40 below 35 ms and delta QRS below 13 ms. Late potentials were present when at least one of these criteria was positive. When these norms were applied to patients with sustained ventricular tachycardia the prevalence of late potentials was 76%, rising to 90.4% in the subgroup of 21 patients with coronary disease. With the method thus defined the specificity for each criterion taken separately is 97.5%. According to the norms, only one control subject (0.8%) gave a false-positive result.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Effects of trimetazidine on a model of in vitro myocardial ischemia].

Cardioprotection is a new concept proposed for clinical situations as myocardial infarction and cardiac surgery. Cardioprotective effects are mainly evaluated in patients by enzymatic, electrocardiographic and sometimes histological findings. The aim of this work was to study the effects of trimetazidine on guinea-pig ventricular myocardium submitted in vitro to conditions mimicking ischaemia. A three step procedure was used: a period of stabilization of 180 minutes under control conditions, then a period of 60 minutes under ischaemic conditions, and last a replacement into control conditions perfusion (30 minutes). Trimetazidine was added in the superfusion during the last hour of stabilization and maintained during the ischaemic and the reperfusion periods. Electrical activities (micro-electrodes) and creatine phosphokinase activity in the effluent were monitorized. Trimetazidine (10(-6) M) prolonged during the ischaemic phase the duration of decremental response and improved electrical recovery during reperfusion. Moreover, trimetazidine (10(-6) M) reduced creatine phosphokinase leakage during ischaemia. The effects of trimetazidine were compared to those observed with calcium channel antagonists in the same model. Thus slowing of enzyme leakage and electrical improvement observed under trimetazidine are compatible with a so-called cardioprotective effect.

Animals↗

[Ventricular extrasystole. Which should be treated and how?].

The decision of whether or not to treat a ventricular extrasystole depends in the first instance on the benign or severe nature of the disorder, and on whether there is subjacent cardiopathy. The results of 24-hour Holter monitoring, exercise tolerance tests and clinical and echographic examinations will define the pathological character of a ventricular extrasystole and will indicate any subjacent cardiopathy. Electrophysiological exploration with programmed stimulation should be reserved for so-called lethal cases of arrhythmia, such as attacks of sustained ventricular tachycardia. Ischemic cardiopathy is by far the most frequent cause of ventricular extrasystoles. The two major risks of sudden death after myocardial infarction are due to left ventricular dysfunction and repetitive and/or complex ventricular extrasystoles, as well as to attacks of ventricular tachycardia. Heart patients presenting these disorders must receive urgent treatment with antiarrhythmics. Isolated, monomorphic ventricular extrasystoles are also treated in heart patients at risk if their frequency is greater than 10 per hour, measured by 24-hour Holter monitoring. In the absence of subjacent cardiopathies, the therapeutic indications are much less well defined. Approximately five per cent of subjects in a normal population present ventricular extrasystoles, the frequency of which, however, rarely exceeds 100 per 24 hours. Repetitive phenomena are only seen in 10 per cent of cases. Attacks of ventricular tachycardia are almost never seen. Ventricular extrasystoles that develop in apparently normal hearts, but which do not fulfill the above criteria, can be considered abnormal. Nevertheless, there is no categorical proof that these ventricular extrasystoles represent any risk, notably of sudden death.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗

[Continuous electrocardiographic recording with the Holter method in children. Indications and results].

There are relatively few reported studies of continuous electrocardiographic recordings by the Holter method in children. We report our experience of 296 24-hour recordings in 160 patients (average age 10.5 years), investigated for suspected or known cardiac arrhythmias. One hundred and ten patients (68.75%) had no organic heart disease and 6 patients (3.75%) had acquired lesions. Eighty-three patients (52%) were symptomatic. Sixty-three patients (39%) had normal recordings; 97 patients (61%) had a total of 126 arrhythmias. There were 45 cases of atrioventricular block, 24 cases of sinus node dysfunction, 39 cases of supraventricular arrhythmias and 18 cases of ventricular arrhythmias. Overall, 47.6% of these rhythm disturbances were diagnosed by Holter monitoring. This technique was particularly valuable in the diagnosis of arrhythmias in symptomatic patients, patients with arrhythmogenic cardiac lesions and in the detection and surveillance of postoperative arrhythmias in congenital heart disease, of pacemakers, of congenital atrioventricular block and of the chronic arrhythmias of childhood.

Adolescent↗

Frequency of provoked coronary arterial spasm in 1089 consecutive patients undergoing coronary arteriography.

We established the incidence of coronary artery spasm provoked by 0.4 mg of methergine in 1089 consecutive patients undergoing coronary angiography. The test was performed after routine coronary arteriography. Subjects included patients with angina, both typical and atypical, patients who had recently had myocardial infarction and patients with either valvular disease or congestive cardiomyopathy. Patients with spontaneous spasm, left main narrowing or severe three-vessel disease were excluded. One hundred thirty-four patients experienced focal spasm. Focal spasm was uncommon in patients with atypical precordial pain (1.2%), angina of effort (4.3%), valvular disease (1.95%) or cardiomyopathy (0%). It occurred most often in patients with angina at rest and less often in patients with angina both at rest and induced by exercise. Spasm was provoked in 20% of patients with recent transmural infarction, but in only 6.2% of patients studied later after infarction. Spasm was superimposed on fixed atherosclerotic lesions in 60% of the patients. No serious complications were encountered. Although the patients who underwent provocation tests in this study are not representative of all patients with coronary artery disease, spasm occurred in 20% of patients who experienced a coronary event and in 15% of patients who complained of chest pain.

Adult↗

[Arterial vascularization of the tail of the pancreas].

Concerning acute pancreatitis following splenectomy, the authors studied the arterial blood supply of the pancreas, by means of 30 dissections, injections and radiographies; they described three types of arteries, of which origin, length, diameter, entry-point in the gland and distribution were studied; the vascular etiology pancreatitis following splenectomy does not appear probable.

Arteries↗