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Biomedical subjects

P Lechat

Publications and source records attributed to P Lechat.

At least 19 recordsLinked to original sources
PubMed1992

Cardiomyopathy in Friedreich's ataxia: a Doppler-echocardiographic study.

Heart involvement is frequent in Friedreich's ataxia (FA), the most prevalent of the spino-cerebellar degenerative diseases, which is inherited with an autosomal recessive pattern. However, the pathophysiological link between cardiac and neurological disorders is not yet clearly established. We compared a group of 10 patients with FA to a control group (C) of 16 normal subjects, using Doppler-echocardiography. To see whether cardiac involvement was specific to FA, the data of patients with FA were also compared to those of patients with autosomal dominant olivo-ponto-cerebellar atrophia (OPCA), another spino-cerebellar degenerative disease. There was an increase in left ventricular mass index in FA (154 +/- 9 g.m-2 vs 99 +/- 7 g. m-2 in C, P < 0.001), systolic function was normal, the ejection fraction (EF) slope and E/A ratio were decreased (85 +/- 9 mm.s-1 vs 130 +/- 7 mm.s-1 in C, P < 0.001 and 1.5 +/- 0.1 vs 1.7 +/- 0.1 in C, P < 0.01, respectively), while the isovolumic relaxation period was increased (96 +/- 3 ms vs 92 +/- 2 ms in C, P < 0.01). Deceleration time and time-velocity integrals of A wave to total mitral flow were not modified. In OPCA only the E/A ratio was decreased (1.5 +/- 0.1 vs 1.7 +/- 0.1 in C, P < 0.05). These data show the presence of cardiomyopathy in FA with left ventricular hypertrophy and suggest the presence of diastolic function abnormalities. The cardiomyopathy seems specifically associated with FA and not to spino-cerebellar degenerative disease in general.

Adolescent↗
PubMed1992

Plasma calcitonin gene-related peptide decreases in chronic congestive heart failure.

To investigate the role of calcitonin gene-related peptide (CGRP) in cardiac failure, a sensitive and specific radioimmunoassay was developed to study plasma levels of CGRP in 37 normal subjects and 41 patients with heart failure (HF). The mean plasma levels of CGRP were 294.3 pg.ml-1 (SEM: 41.4) in normal subjects and 121.2 pg.ml-1 (SEM: 21.2) in HF patients. The significant decrease observed in HF patients suggests that CGRP is involved in the pathogenesis of heart failure via a direct effect or via modulation of sympathetic nervous activity.

Calcitonin Gene-Related Peptide↗
PubMed1992

[Non invasive evaluation of cardiovascular effects of nebivolol in patients with cardiac insufficiency].

The results of several studies, mostly without controls, have suggested that betablockers, administered at progressively increasing doses, may be beneficial in cardiac failure. Based on this hypothesis, betablockers with a peripheral vasodilator effect, such as Nebivolol, could be particularly valuable in this indication. A preliminary study of its tolerance, haemodynamic and neurohormonal effects was carried out with a noninvasive methodology in 12 patients with cardiac failure in sinus rhythm, 8 men and 4 women (average age 53 +/- 12 years), all of whom had Class III or IV symptoms according to the NYHA Classification. The protocol had 2 phases: the first was an open phase during which Nebivolol was administered at a dose of 1 mg/day for 48 hours then 2.5 mg/day for 72 h. In the second phase, the patients were randomly separated into 2 groups, one to receive placebo and the other 2.5 mg for one week then 5 mg of Nebivolol for the 5 remaining weeks. The heart rate decreased significantly from 70 +/- 3 to 63 +/- 4 beats/min (p < 0.01) with Nebivolol 1 mg/day without further slowing at the 2.5 mg dosage. During the randomised phase, the heart rate remained stable in the Nebivolol group but increased to its initial value in the group given placebo. No aggravation of symptoms was observed in the Nebivolol group. No significant changes in cardiac output, parameters of cardiac loading or contractility could be demonstrated after 6 weeks' treatment. During submaximal exercise testing, plasma concentrations of catecholamines and atrial natriuretic factor tended to be higher with Nebivolol than with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1992

[Nitrate derivatives and cardiac insufficiency].

Nitrate derivatives are venous vasodilators which are effective in reducing the symptoms of pulmonary congestion. The beneficial action on exercise capacity was recently demonstrated in the Veterans II Study in association with Hydralazine and has also been suggested by other trials. The reduction in mortality from cardiac failure was demonstrated in the Veterans I Study in association with Hydralazine compared to conventional digitalo-diuretic therapy but seems less important than that obtained by angiotensin converting enzyme inhibitors. The phenomenon of tolerance seems to be related to the use of high doses in continuous therapy and may be countered by discontinuous use of the drug during the 24 hour period. Tolerance seems to be related to neuro-hormonal factors and perhaps to depletion of SH groups. Simultaneous use of nitrates and ACE inhibitors seems to be an interesting therapeutic concept.

Aged↗
PubMed1991

Quantitative high-performance liquid chromatographic, gas chromatographic, and gas chromatographic-mass spectrometric analysis of ticlopidine in baboon plasma after solid-phase extraction.

High-performance liquid chromatography with UV detection (HPLC-UV) and gas chromatography with either nitrogen phosphorus (GC-NPD) or mass spectrometry (GC-MS) detection were used for the determination of ticlopidine in plasma. Solid-phase extraction of ticlopidine from plasma was performed using Extrelut columns without pH adjustment, and using hexane as the solvent of elution. With HPLC, a mobile phase of 0.01 M pH 7.8 phosphate buffer:acetonitrile (70:30) was passed through a mu Bondapack C-18 column at a rate of 1.3 mL/min. Ultraviolet detection at 235 nm was sensitive to plasma ticlopidine concentrations of 0.05 micrograms/mL. The GC-NPD and GC-MS were performed on a DB-17 fused-silica column using on-column injection. For GC-NPD and GC-MS, limits of quantification were found to be 0.020 and 0.005 micrograms/mL, respectively. Compared with HPLC-UV, the GC methods were found to be more reproducible, sensitive, and specific and therefore more suitable for pharmacokinetic applications.

Animals↗
PubMed1991

[Search for emboligenic heart disease in case of ischemic cerebral accidents].

The demonstration of a cardiac source of systemic embolism in patients who have suffered a cerebral ischemic event may have important therapeutic implications. This explains the large demand for echocardiography and Holter monitoring in these patients. The frequency of cerebral embolism of cardiac origin, the simplification of the diagnostic approach by non-invasive investigations and the precision of ultrasound techniques explains the tendency towards the indiscriminate generalisation of this attitude. However, the large number of potential patients for investigation, the limited facilities of investigation and the incertitude over the responsibility of certain cardiac abnormalities with respect to the context and age, are arguments in favour of a more selective investigative approach. The keystone of diagnosis is careful history taking and clinical examination with interpretation of the ECG and chest X-ray. Three clinical situations may then be identified: 1) A cardiac abnormality known to be highly embolic is diagnosed from the outset (e.g. mitral stenosis, valve prosthesis, endocarditis, myocardial infarction). The diagnostic work-up is no longer etiological: echocardiography may show intracardiac thrombi or a valvular vegetation, reinforcing the causal relationship, but the complementary investigations are mainly useful for evaluation the cardiac disease and for deciding on curative or preventive therapy. 2) A cardiac abnormality is diagnosed but its responsibility is doubtful due to its high prevalence and low embolic potential. This is the case of patients with mitral valve prolapse, mitral annular calcification, calcific aortic stenosis and VVI pacing. Complementary investigations are not discriminative for the etiological diagnosis of the cerebral embolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1991

[Value of 5-HT3 receptor antagonists, particularly as anti-emetic drugs].

Several binding sites for serotonin or 5-hydroxytryptamine (5-HT) were identified by using selective agonists and antagonists. Today, 5-HT3 receptor types are considered to occupy a critical position in the emetic pathway. The discovery of 5-HT3 receptor antagonists originated from metoclopramide, an antidopaminergic drug introduced in France 25 years before as a modifier of digestive motricity; it represents a therapeutic advance, since it led to the first class of antiemetic drugs specifically designed to prevent severe cytotoxic drugs-evoked emesis and devoid of noticeable side-effects. It must be emphasized upon the necessity of developing new experimental tests in living animals and performing controlled trials on patients under chemotherapy to achieve this progress.

Antiemetics↗
PubMed1979

Chronotropic effect of histamine on cultured neonatal rat heart cells.

The positive chronotropic effect (PCE) of histamine in cultured neonatal rat heart cells was monitored using a microscopic method as well as an electro-optically recording device. The action potential frequency was also measured (by means of microelectrodes). An increase in PCE was noted when histamine (from 1 X 10(-6) M to 1 X 10(-5) M) was added to the cells. However, higher concentrations (from 1 X 10(-5) M to 1 X 10(-4) M) were less effective. The PCE of histamine was reduced by pretreating the cells with antihistaminic drugs. H1-blocking agents (promethazine and mepyramine) were more potent than H2-blocking drugs (metiamide and cimetidine). In addition, the PCE of histamine was abolished when the cells were in presence of high K+ medium (26 mEq) but contraction and action potential amplitudes were increased. Our results demonstrate that these cultures respond to histamine and that this response is abolished by antihistaminic drugs thus suggesting the H1 and/or H2 receptors may be present in the neonatal rat heart cell cultures.

Animals↗
PubMed1979

Inhibitory effect of kanamycin on evoked transmitter release. Reversal by 3,4-diaminopyridine.

The effect of kanamycin (Kn) on evoked transmitter release was examined in frog end-plates in vitro. By a presynaptic action, Kn (0.02 to 1 mM) significantly reduced the amount of acetylcholine liberated by nerve stimulation. In addition to its presynaptic effects, Kn (0.96 mM) decreased the size of the miniature end-plate potentials possibly by acting at the postsynaptic level. 3,4-Diaminopyridine (4.5 microM) reversed the presynaptic effects of Kn but did not modify its postsynaptic action.

Aminopyridines↗
PubMed1979

[Reduction of isoprenaline induced tachycardia in pregnant rats. Role of a serum factor].

The in vivo isoprenaline (50 microgram/kg) induced tachycardia (beta 1 adrenergic stimulant effect) was decreased in pregnant (20th day) Rats compared to non pregnant Rats. The in vitro positive chronotropic effect of isoprenaline (10 ng/ml) on cultured Rat heart cells was abolished by pregnant Rat serum whereas progesterone (0.10 to 5 microgram/ml) or oestradiol (0.1 to 25 microgram/ml) were ineffective. The decreased beta 1 adrenergic responsiveness in pregnant Rats could be related to a seric factor, different from these two hormones.

Animals↗
PubMed1979

Analysis of the action of 4-aminopyridine during repetitive stimulation at the neuromuscular junction.

4-Aminopyridine (4-AP) increased the quantal content (m) of end-plate potentials (e.p.p.s) evoked by continual stimulation (0.2--25 Hz) in frog end-plates depressed by Mg2+. The increase in m was due to an increase in the binomial parameter n. This was interpreted to mean that 4-AP increased the number of activated release sites. In junctions blocked by d-tubocurarine, 4-AP first increased and then decreased the amplitude of e.p.p.s. elicited during a train of stimuli of increasing frequency, indicating that 4-AP increased transmitter release more than mobilization.

Aminopyridines↗
PubMed1979

Effect of human chorionic gonadotrophin on phagocytic activity and proliferative capacity of rat peritoneal macrophages in culture.

Human chorionic gonadotrophic hormone (hCG) decreased phagocytosis of rat peritoneal macrophages in culture and also inhibited their capacity to be stimulated by an inflammatory exudate. Both effects were related to the concentration used. These experimental results suggest that elevated levels of hCG may play a role in the prevention of the rejection of the foetal allograft by the maternal host.

Animals↗
PubMed1979

[Biological determination of the beta blocking activity of human serum].

A method of biological assessment of the Beta blocking activity of human serum is reported. It is based on the catecholamine response of rat myocardial cells in culture, incubated in the serum to be tested. Its advantage is that it takes into account all block-blocking substances present in the serum, not only the drug itself but also its possible active metabolites. The results obtained by this method in 10 healthy subjects after 60 mg penbutolol were compared with those given by chemical dosage and ergometry. The ergometric and biological changes were parallel from the 2nd and the 8th hour while the serum levels of the drug rapidly. This discordance could be due to the presence of an active metabolite, 4-hydroxy-penbutolol.

Adrenergic beta-Antagonists↗
PubMed1978

Inhibited response to isoproterenol and altered action potential of beating rat heart cells by human serum in septic shock.

Human serum, obtained within 24 hours after the onset of septic shock, was evaluated for its effects on the chronotropic response of cultured rat myocardial cells to isoproterenol. Transmembrane action potential (AP) was measured in some experiments. Sera obtained after the first four to five hours, when central venous pressure (CVP) was normal or high, inhibited increased cell beats, while this property was not evidenced for samples taken soon after septic shock when CVP was low. Sera were also found to alter AP in much the same way as Sotalol, an adrenergic beta-blocking drug. These two effects were never observed with control sera obtained from healthy male adults at rest. These findings demonstrate that sera from patients in septic shock depress the beta-adrenergic response of rat myocardial cells, after the early phase of septic shock characterized by sympathoadrenergic activity. They strongly suggest the mediation of unidentified humoral factors, which might interfere in the pathogenesis of myocardial dysfunction during the intermediate phase of septic shock.

Action Potentials↗