Biomedical subjects
Publications and source records attributed to P Lechat.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In pentobarbitalized closed-chest dogs, nicergoline (10--100 microgram/kg, i.v.) reduced blood pressure, heart rate, and splanchnic nerve activity. Intracisternal administration of nicergoline (3 microgram/kg) only reduced splanchnic nerve activity. In open-chest dogs, nicergoline reduced blood pressure, cardiac output, and total peripheral resistance but did not change heart rate. In pithed rats treated with a beta-adrenoceptor-blocking agent, nicergoline reduced the pressor responses to noradrenaline and adrenaline. Nicergoline slightly attenuated the pressor responses of dogs to noradrenaline and tyramine and, in addition, reversed the hypertension induced by adrenaline and dimethylphenylpiperazinium. Nicergoline (100 microgram/kg) increased the tachycardia induced in dogs by stimulation of the right cardiovascular nerve and prevented the inhibitory effect of clonidine on this response. However, nicergoline only partially antagonized the effect of clonidine once it was fully established. Nicergoline did not antagonize the hypotensive and bradycardic effects of clonidine when they were established. Nicergoline did not affect the vagally mediated bradycardia evoked by carotid nerve stimulation in beta-adrenoceptor-blocked dogs. The compound did not change blood pressure in Cl spinal cord transected dogs. In conclusion, nicergoline appears to decrease blood pressure by blocking alpha-adrenoceptors and, at least at some doses, by a central inhibition of the sympathetic tone. Nicergoline appears to be a preferential alpha 1-adrenoceptor-blocking agent.
Beraprost sodium (BPS), an orally active PGI2 (prostaglandine 12) analogue possesses vasodilatating and platelet aggregation inhibiting properties. It is being developed in peripheral arterial occlusive disease. As in future clinical practice BPS might be co-prescribed with oral anticoagulants, we investigated its interaction with fluindione, a vitamin K antagonist in healthy subjects in a randomised, double-blind, placebo-controlled, crossover study. Twelve healthy Caucasian male subjects randomly received BPS 40 microg t.i.d. or placebo for 3 days. There was a 7 day wash out between the two treatment periods. On day 3 of each treatment, the subjects ingested concomitantly a single oral dose of 20 mg of fluindione. The main assessment criterion was fluindione's pharmacokinetics. Secondarily, pharmacodynamic measurements of coagulation (prothrombin time, and International Normalised Ratio, INR) and platelet function (in vitro closure time assessed by PFA-100) were performed. Fluindione was assayed by HPLC with UV detection up to 96 h post-drug. No statistical difference could be evidenced on any fluindione pharmacokinetic parameters between BPS and placebo phases: t 1/2 (h): 35.9 (8.2) vs. 34.0 (4.2) [90% CI 105.8 (95.5-116.2)]; T(max) (h): 2.0 (0.5-6.0) vs. 4.0 (0.5-6.0) [90% CI 136.4 (70.7-208.9)]; Cmax (mg/L): 3.1 (0.6) vs. 2.9 (0.5) [90% CI 94.1 (85.8-103.2)]; AUC 0-inf (mg/h/L): 117.0 (31.5) vs. 113.9 (33.8) [90% CI 97.6 (87.5-108.8)]. The studied doses of BPS did not affect platelet function, at least as assessed by the in vitro platelet function testing. Twenty milligrams of fluindione marginally modified the PT ratio and INR, however, no statistically significant difference was found between BPS and placebo phases. In conclusion, a 3 day regimen of BPS 40 microg t.i.d. by oral route does not seem to affect pharmacokinetic parameters of a fluindione 20 mg single dose.
Explore the source record for details and available documents.
The glucocorticosteroids are derived chemically from androsterone or pregnane. Their natural models are cortisone and cortisol (or hydrocortisone), characterised by the presence of oxygen or an oxydryle group at 11, of a --CO -- CH2OH group in the 17 position and of an-OH group in the 17 position. Their anti-inflammatory power dominate their pharmacodynamics: it goes hand in hand with their power to increase gluconeogenesis. They have an immunodepressant effect whose power seems to be proportional the their anti-inflammatory action. The use of hydrocortisone in the treatment of shock remains empirical. The mechanism of their anti-allergic effect remains debated. Glucocorticosteroids disturb lipid and protein metabolism, water and electrolyte balance, the central nervous system, and gastric secretion; they inhibit the secretion of ACTH. Their pharmaceutical forms are numerous: they are adapted to the oral route and to the parenteral routes (i.m., i.v., i.r., intra-articular) and to external use (cutaneous and mucosal applications).
BACKGROUND: A combination of low-dose aspirin (A) and anticoagulation (AC) may provide better protection against thromboembolic events compared with AC alone in high-risk patients with atrial fibrillation (AF). METHODS: We performed a multicentric placebo-controlled double blind-trial to test the preventive efficacy against thromboembolic events of the addition of aspirin (A) (100 mg) or placebo (P) to anticoagulant treatment in patients with high-risk atrial fibrillation. A total of 157 patients were included, with atrial fibrillation and previous thromboembolic event or older than 65 years with either a history of hypertension, a recent episode of heart failure or a left ventricular dysfunction. All patients received fluindione (F) and P or F and A, with an INR target between 2 and 2.6. The primary endpoint was a combined endpoint of stroke (ischaemic or haemorrhagic), myocardial infarction, systemic arterial emboli or vascular death. RESULTS: The study had to be stopped prematurely owing to a too low recruitment rate. During follow-up (0.84 years) 3 non-fatal thromboembolic events were recorded (1P, 2A) and 6 patients died (3P, 3A), none of them from a thromboembolic complication. However, 3 deaths were secondary to severe haemorrhagic complications (1P, 2A). Non-fatal haemorrhagic complications occurred more often in group A (n = 10, 13.1 pour cent) compared with group P (n = 1, 1.2 pour cent), p = 0.003. CONCLUSION: The FFAACS study was not able to show any therapeutic benefit from the addition of aspirin to anticoagulant in patients with high-risk AF. Such a combination increased the incidence rate of bleeding complications, which therefore greatly reduces its potential overall benefit.
After a significant mortality benefit with bisoprolol in heart failure was demonstrated in CIBIS-II, an economic evaluation has been performed in cost-effectiveness terms. Average direct costs per patient were based on clinical data from 231 French patients, and measured in the perspective of the French National Health Insurance, effectiveness being expressed in terms of life days gained per patient. The extra cost of bisoprolol treatment and follow-up (averaging FF 1300 per 1.3 years) is outweighed by the reduction in hospitalization costs (representing a saving of FF 10,500 per patient) and other medication costs. Finally, bisoprolol therapy induces benefits in terms of both cost and survival: on average FF 9500 and 11 life days per patient. Sensitivity analyses confirm these results.
Animal experiments are scientifically justified to establish kinetic parameters of xenobiotics in vivo (absorption, diffusion, biotransformation, elimination of pesticides, food additives and drugs). They are indispensable for evaluating toxic effects which appear with delay (carcinogenesis, drug dependence), and for exploring reactions which involve complex regulating systems in the whole organism. In this field, methods are in progress, leading to use less and less animals and to obtain more accurate data. Some problems still exist concerning painful experiments and controls of local tolerance. In vitro assays must not be opposed against those performed in vivo, since both are complementary and must be coordinated in order to make fruitful progresses for the benefit of men but also of animals.
Prognosis of heart failure patients remains poor and stimulates research of new active drugs and therapeutic improvements. Besides diuretic and vasodilating agents, the place of positive inotropic drugs remains to be defined. Long term benefit remains to be demonstrated for Milrinone, Enoximone and Digitalis. However, absence of benefit has been established with Amrinone and beta adrenoceptor agonists. Too many uncontrolled studies have complicated the accurate evaluation of efficacy of these positive inotropic drugs. Purpose of heart failure treatment remains to improve functional status without deterioration of myocardial fibers contractility. The respective roles of cAMP, gAMP and intracellular calcium concerning myocardial fiber longevity remains to be clarified.
We investigated the anti-ischemic effects of PK 11195 (RP 52028), a selective ligand for peripheral type benzodiazepine binding sites in man. In a first series of patients, we did not find any hemodynamic effect of 10 mg (8 patients) or 20 mg (8 patients) of the intravenously administered drug. The anti-ischemic effect was evaluated on 16 patients with coronary heart disease and a positive stress test in a double blind study of 20 mg of intra-venous PK 11195 (8 patients) versus placebo (8 patients). Ischemia was induced by pacing, and assessed by ST segment depression and lactates extraction before and 15 minutes after administration of the drug. No statistical differences could be found on these ischemia indices between the placebo and PK 11195 treated groups. Although experimental studies have shown interaction of the drug with the calcium channels, our study did not demonstrate any anti-ischemic effect with the dosage used.
Today paracetamol (acetaminophen), the oldest known synthetic analgesic-antipyretic drug, is one of the most frequently used around the world. The present general review presents the essential knowledge about this drug which has accumulated during the last decade, 1978 from to 1988. It includes recent data concerning toxicity, pharmacokinetics, mechanisms of analgesic and antipyretic action, and therapeutic efficacy. Readers interested in the original papers are referred to 264 bibliographical references.
In the French Pharmacopoeia there is a table of doses of drugs for pediatric use, which is to be hold as an official document. Some of the problems raised for establishing these doses are discussed in this paper: choice of age-ranges, selection of drugs, way of expressing doses, interest or not to indicate maximal doses, spread of these data to medical prescribers and pharmacists.
Explore the source record for details and available documents.
It should be possible to detect heart transplant rejection by nuclear magnetic resonance (NMR) imaging if it induces myocardial T1 and T2 proton relaxation time alterations or both. We studied 20 Lewis rats after a heterotopic heart transplantation. In vitro measurement of T1 and T2 was performed on a Minispec PC20 (Bruker) 3 to 9 days after transplantation. Histologic analysis allowed the quantification of rejection process based on cellular infiltration and myocardiolysis. Water content, a major determinant of relaxation time, was also studied. T1 and T2 were significantly prolonged in heterotopic vs orthotopic hearts (638 +/- 41 msec vs 606 +/- 22 msec for T1, p less than 0.01 and 58.2 +/- 8.4 msec vs 47.4 +/- 1.9 msec for T2, p less than 0.001). Water content was also increased in heterotopic hearts (76.4 +/- 2.3 vs 73.8 +/- 1.0, p less than 0.01). Most importantly, we found close correlations between T1 and especially T2 vs water content, cellular infiltration, and myocardiolysis. We conclude that rejection reaction should be noninvasively detected by NMR imaging, particularly with pulse sequences emphasizing T2.
Explore the source record for details and available documents.
Explore the source record for details and available documents.