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Biomedical subjects

P Lechat

Publications and source records attributed to P Lechat.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1991

Immune status and survival of opiate- and cocaine-treated mice infected with Friend virus.

In as much as the immunomodulatory effects of opiates and cocaine are known to modify spontaneous host defenses against infection, we investigated the effects of morphine, pentazocine and cocaine on the time course of Friend virus infection in mice. Repeated i.p. injections with increasing doses of morphine hydrochloride (10-100 mg/kg for 10 days before infection, a dose regimen which induced tolerance to the acute antinociceptive effects of the drug, followed by 30 mg/kg for 14 days postinfection) did not increase the mortality due to Friend virus infection. This regimen did not significantly affect the immune response of infected mice assessed in terms of delayed hypersensitivity (ear thickness) and the hemagglutination assay. In contrast, a single challenge with a large dose of morphine (up to 300 mg/kg), which is not lethal in noninfected mice, increased mortality markedly (up to 100%) in infected mice when administered at day 14 or 21 postinfection. Repeated i.p. injections with pentazocine (50 mg/kg b.i.d. for 5 days before infection, followed by 30 mg/kg for 14 days postinfection) had no influence on mortality or immune responses in infected mice; similar results were obtained with a single high-dose injection (up to 100 mg/kg). Lastly, repeated i.p. injections of cocaine, using the same experimental procedure as that for pentazocine, decreased immune responsiveness and slightly increased mortality, whereas a single injection was devoid of lethal effect. These findings suggest that chronic opioid treatment does not lower host resistance to viral infection but that the latter could increase the toxicity of a single high dose of morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Beta-blockers in the treatment of heart failure].

The first attempts at treating heart failure with beta-blockers were made almost 15 years ago. A few studies, some of them controlled and randomized, suggest that beta-blockers may improve the patients' comfort, their physical capabilities, their haemodynamic values or even their life expectancy. However, the results published are conflicting. The mechanism of the beneficial effects of beta of beta-blockers is controverted, the most widely accepted hypotheses being that they protect against the toxic effect of catecholamines, act as antiarrhythmics and prevent the down regulation of beta-adrenoceptors. Numerous questions concerning the exact indications of these drugs, the nature and dosage of the beta-blocker to be used, the possible combinations with other therapies and the responses to be expected remain to be answered. When available, the results of multicentre trials currently in progress will be of assistance to determine the role of beta-blockers in the overall management of heart failure.

Adrenergic beta-Antagonists↗
PubMed1990

Beta-blockade treatment in heart failure: the cardiac insufficiency bisoprolol study (CIBIS) project. CIBIS Committees and Investigators. Cardiac Insufficiency Bisoprolol Study.

The efficacy of treatment with diuretics and vasodilators in heart failure has shown that compensatory mechanisms may induce vicious circles that can precipitate the deterioration of congestive heart failure (CHF). By counteracting sympathetic stimulation of cardiac beta-receptors, beta-blocking drugs could provide some benefit in CHF. Indeed, the sympathetic stimulation enhances metabolic costs and could lead to a further deterioration of myocardial fiber function. This could be counteracted by beta-blockade. On the contrary, the loss of adrenergic responsiveness due to beta-adrenergic downregulation and depletion of norepinephrine stores from sympathetic nerves could be responsible for the progressive deterioration of cardiac function. Moderate doses of beta-blocking agents could restore such a catecholamine sensitivity by upregulation of beta-receptors and restoration of norepinephrine stores. Results of clinical trials with beta-blockade in CHF are so far controversial. Most studies enrolled patients with cardiomyopathy and included small numbers of patients or were uncontrolled. The CIBIS trial (Cardiac Insufficiency Bisoprolol Study) has been launched in Europe to answer the question of the potential benefit on prognosis of beta-blockade therapy in heart failure from any etiology, especially ischemic CHF. It is a randomized, placebo-controlled, double-blind multicentric trial involving two parallel groups of patients (300 in each group) followed over a 2-year period. Results from the CIBIS trial should provide conclusive information concerning the use of beta-blocking therapy in CHF.

Adrenergic beta-Antagonists↗
PubMed1990

[Noninvasive evaluation of partial beta adrenergic agonist properties of xamoterol in cardiac insufficiency].

The effects of an intravenous injection of 0.15 mg/Kg of xamoterol were studied non-invasively under basal conditions and during beta-1-adrenergic stimulation with dobutamine in 16 patients with dilated cardiomyopathy and severe cardiac failure. Xamoterol did not cause any detectable agonist effect but was well tolerated under basal conditions. Its potential antagonist effect was only detected during the dobutamine infusion: xamoterol significantly reduced the increase in heart rate (p less than 0.001), the systolic blood pressure (p less than 0.01), the rate-pressure product (p less than 0.001) and the cardiac index (p less than 0.001) produced by the administration of dobutamine.

Adrenergic beta-Agonists↗
PubMed1989

Evidence that clomethiazole interacts with the macromolecular GABA A-receptor complex in the central nervous system and in the anterior pituitary gland.

Clomethiazole (CLOM) is known to be an anticonvulsant drug and has been also reported to decrease serum prolactin (PRL) in humans. Both effects may be mediated by an enhancement of gabaergic transmission. In order to determine if (CLOM) interacts with GABA metabolism and/or at the GABA receptor level, we studied its effect on PRL release and on the binding of various compounds that interact with the GABAA-benzodiazepine-receptor complex. Intraperitoneal (IP) administration of CLOM to rats significantly decreased PRL levels, and this effect was antagonized by IP administration of bicuculline, an antagonist of the GABAA receptor. In vitro, the inhibitory effect of muscimol on PRL release from rat hemiadenohypophysis was potentiated in a dose-dependent manner by preincubation with CLOM. This effect was antagonized by picrotoxin (10(-6) M). On the other hand, CLOM had no effect on GABA metabolism and did not compete with GABAA, GABAB or benzodiazepine binding sites in cortical membranes. CLOM competed, however, with the picrotoxin binding site labelled with [35S]-butylbicyclophosphorothionate (TBPS), at an IC50 value of 1.2 x 10(-4) M, which is in the same range as some barbiturates. These results concerning PRL release and binding experiments with cortical membranes suggest that CLOM interacts with the picrotoxin/barbiturate site of the GABAA-receptor-chloride channel complex.

Animals↗
PubMed1989

Dependence on extracellular potassium of the positive inotropic response to St 587, a selective alpha-1 adrenoceptor agonist, in Zucker rat heart ventricle.

The effects of St 587, a selective alpha-1 adrenoceptor agonist, were investigated in non obese and obese Zucker rat heart ventricles. In both groups, the numbers and affinity constants for alpha-1 adrenoceptors were found to be similar. At 4 or 10 mM [K]o, St 587 failed to increase the developed tension whereas at 14 mM [K]o, St 587 significantly increased it in both groups of rats. This effect was reversed by prazosin; St 587 also increased action potential duration at 14 mM [K]o. [K]o is thus important for the occurrence of the inotropic effect of St 587 in 12 week-old Zucker rats, either non obese or obese with reduced beta-adrenoceptor responsiveness. This suggests the participation of phosphoinositide metabolism in the mechanism of St 587 inotropic effect in the rat.

Action Potentials↗
PubMed1989

Effects of some antimalarial drugs on rat inflammatory polymorphonuclear leukocyte function.

In vitro concentrations of chloroquine, amodiaquine, quinine, and mefloquine were assessed with respect to functional responses (chemotaxis, anion superoxide generation, and lysosomal enzyme release) of rat polymorphonuclear leukocytes (PMN) collected after induction of acute pleural inflammation. Chloroquine, amodiaquine, and mefloquine exhibited dose-dependent inhibition of: (1) random migration and oriented migration of PMN; and (2) opsonized zymosan- or phorbol myristate acetate-stimulated PMN O2- release. These effects were not stimulus-specific and were largely reversed by washing the cells before stimulation Mefloquine was the most effective drug. Quinine had no effect on PMN migration. Apart from quinine, the drugs induced similar dose-dependent increases in beta-glucuronidase release from unstimulated PMN. Only quinine inhibited the enzyme release from stimulated PMN. Our data show that the antimalarial derivatives affect PMN functions in various ways and suggest that their effects reflect nonspecific modifications of cellular membrane.

Animals↗
PubMed1989

[Echocardiographic detection of adriamycin cardiotoxicity. Study of the relationship between the shortening fraction-constraint and the systolic shortening fraction-diameter of the left ventricle].

Cardiotoxicity is the main obstacle to the use of high-dosage adriamycin in chemotherapy. It is difficult to decide whether or not treatment should be continued when the cardiac function -- irrespective of the method by which it is evaluated -- is at the lower limit of normality. Some authors consider that chemotherapy can be pursued as long as the shortening fraction of the echocardiographic diameter remains within normal limits in relation to the end-systolic constraint. We have established the limits of normality of this relationship before chemotherapy in 53 patients with normal cardiovascular system. We conclude that the end-systolic constraint essentially depends on the end-systolic diameter, so that the results provided by the study of the shortening fraction end-systolic constraint relationship are qualitatively the same as those of the shortening fraction-end-systolic diameter relationship, which is much easier to obtain. It seems to us that the criteria of cardiotoxicity after administration of adriamycin 300 mg/m2 are: (1) shortening fraction lower than 25 p. 100; (2) ventricular dilatation (end-systolic diameter greater than 40 mm) without associated valve disease; (3) reduction of the shortening fraction (whatever its value) in relation to the end-systolic diameter by more than 2 standard deviations on the regression slope of the correlation; (4) more than 25 p. 100 reduction of the shortening fraction after administration of adriamycin 300 mg/m2, betraying a high sensitivity to the cardiotoxic effects of the drug. Such individual sensitivity, studied in 25 patients, seemed to vary widely from one subject to another and to be independent of the initial status.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Prevalence of patent foramen ovale in young patients with ischemic cerebral complications].

We compared the prevalence of patent foramen ovale (PFO), detected by two-dimensional contrast echocardiography, in a group of 60 adults aged under 55 who had experienced a cerebral ischaemic accident and had normal standard examination of the heart, and in a control group of 100 patients. The prevalence of PFO was significantly higher in neurological patients (40 p. 100) than in controls (10 p. 100; p less than 0.001). Within the neurological group, the prevalence of PFO determined blindly, i.e. without any knowledge of the aetiological diagnosis, increased with the uncertainty of diagnosis: 21 p. 100 when a cause could be determined (n = 19), 40 p. 100 when a facilitating factor of cerebral accident, such as mitral valve prolapse, migraine or consumption of oral contraceptives, could be identified (n = 15), and 54 p. 100 when neither cause nor facilitating factor could be found (n = 26; p less than 0.10). In view of the very high prevalence of clinically silent venous thrombosis, these results suggest that paradoxical embolism through a PFO might be responsible for cerebral ischaemic accidents more frequently than is generally believed.

Adult↗
PubMed1989

[Contribution of perindopril to the treatment of chronic congestive cardiac insufficiency. Multicenter pilot double blind study versus placebo].

Cardiac decompensation occurred in three patients of the placebo group, but not in the perindopril group. The effectiveness of perindopril in heart failure was demonstrated by the improvement observed in exercise test and severity score and by the decrease of cardiothoracic ratio. Changes in SAP, and serum creatinine levels, in particular, showed that the drug was well tolerated.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

[Evolution of the primary successes of percutaneous aortic valvuloplasty].

Between November 1985 and August 1988, we performed 89 percutaneous aortic valvuloplasties. Sixty-two of these were considered a primary success on the basis of two main criteria: stage I or II on discharge and greater than 50 p. 100 increase in aortic valve area. The mean age of these patients was 78.4 +/- 6.1 years. On actuarial analysis, after 5 months 98 p. 100 of the patients with primary success were alive and 89 p. 100 were in stage I or II and had not been operated upon or redilated. At 15 months 79 p. 100 of the patients with primary success were alive, but only 48 p. 100 were in stage I or II and neither operated upon or redilated. Ultrasonic data obtained one and twelve months after dilatation were compared in 8 patients who had kept the full functional benefit of angioplasty for 14.6 +/- 4.3 months (group 1) and 9 patients who had lost this initial benefit (group 2). In group 1 patients the aortic valve area had moderately and non significantly diminished from 0.92 to 0.72 cm2. In group 2 patients the aortic valve area had gone down from 0.89 to 0.63 cm2 (p less than 0.01), indicating restenosis. We conclude that after the 4th post-valvuloplasty month the medium-term success of the procedure undergoes some degradation, and in these patients the echocardiographic signs of stenosis are clear-cut.

Aged↗
PubMed1989

Value of perindopril in the treatment of chronic congestive heart failure. Multicenter double-blind placebo-controlled study.

Right cardiac catheterization studies have demonstrated an improvement in cardiac hemodynamics in patients with heart failure following the administration of perindopril (per): reduction in ventricular filling pressures (pulmonary capillary wedge pressure, right atrial pressure) and systemic resistance and an increase in cardiac output. The intensity and duration of these modifications were frequently insufficient after 2 mg, but were significant over 24 hours after 4 mg. A randomized, double-blind multicenter study versus placebo (pla) was conducted for 3 months, following a preinclusion period of 15 days, in 103 heart failure patients (stages II and III of the NYHA classification) treated with diuretic +/- digitalis. The following parameters were evaluated before (be), after 1 month (1m) and after 3 months (3 m) treatment: duration of stress test (DST) (sec), clinical severity score (SS), cardiothoracic ratio (CTR), serum creatinine (Cr) (mumol/l), systolic blood pressure (SBP) (mm Hg) in the supine (s) and erect (e) positions. 50 patients received per and 53 received pla; 46 patients in each group completed the double-blind period. Perindopril was administered at doses of 2 mg (n = 6) and 4 mg (n = 40). The following results were obtained: (table; see text) Three cases of acute heart failure occurred in the placebo group compared with none in the peridopril group. The efficacy of perindopril in heart failure was demonstrated by the improvement in effort capacity and severity score and by the reduction in cardiothoracic ratio. The variation in SBP and serum creatinine, in particular, reflected the good safety.

Angiotensin-Converting Enzyme Inhibitors↗