Search PubMed⌕ Search

Biomedical subjects

J M Alexandre

Publications and source records attributed to J M Alexandre.

At least 19 recordsLinked to original sources
PubMed1998

[French system of drug surveillance].

The French drug surveillance system is characterized by: a network of thirty one regional drug surveillance centres, located to provide convenient proximity to health care professionals; a causality assessment method, compulsory for all persons involved in drug surveillance, to assess the causal relationship between an adverse effect and one or more drugs; if necessary, an additional evaluation of the causal relationship will be performed using pharmaco-epidemiology methods; a Technical committee and a National Commission of Drug Surveillance which centralize and assess all the data in order to provide a consensual advice to the relevant authorities on necessary measures, to prevent, or reduce a drug related adverse effect; in the case of an inquiry, the drug surveillance department of the pharmaceutical company and the network of regional drug surveillance centers will pool their data with the aim to exchange information and ideas.

Adverse Drug Reaction Reporting Systems↗
PubMed1988

[Clinical evaluation of drug interactions of cyclosporin].

Cyclosporin is a nephrotoxic immunosuppressant metabolized in the liver and requiring drug monitoring. Numerous pharmacokinetic and pharmacodynamic drug interactions have occurred with this compound. Some of them are well substantiated while others are merely suspected. The major interactions must definitely be prevented of corrected, whereas the others need no more than careful drug monitoring.

Aminoglycosides↗
PubMed1987

Rationale for ACE inhibition in the elderly: treatment of arterial hypertension with enalapril.

A randomized, double-blind, placebo-controlled trial was conducted with 32 elderly patients (aged 75-97 years) with uncomplicated essential hypertension, to evaluate the efficacy and tolerance of enalapril, an angiotensin-converting enzyme inhibitor. It was given over an 8-week period in doses from 20 to 40 mg/day and was compared with an identical placebo. Enalapril caused a significant reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) by the 2nd week, an effect that persisted through to the 8th week (190 +/- 16/102 +/- 7 to 151 +/- 19/85 +/- 11 mm Hg); 67% of patients had their pressures normalized (less than 160/95 mm Hg). BP was also significantly decreased by the 8th week under placebo (183 +/- 16/101 +/- 9 to 165 +/-21/91 +/- 13 mm Hg), but only 35% of patients attained a normal pressure. Heart rate did not change with treatment. Enalapril caused an increase in plasma renin activity (1.22 +/- 0.08 to 3.66 +/- 2.50 ng/ml/h), whereas aldosterone levels remained unchanged. There was a mild, significant elevation of creatinine level with enalapril but other laboratory parameters, including serum potassium, were unaltered. Two deaths occurred in the enalapril group, but were not considered to be treatment-related. The drug was otherwise well tolerated. Serum enalapril concentration was assessed in 10 patients taking 20 mg/day over an 8-day period. At equilibrium, the level was 22.3 +/- 5.0 ng/l and it correlated both with converting enzyme inhibition and with renal function. Enalapril is shown to be an effective and well-tolerated antihypertensive medication in elderly patients.

Age Factors↗
PubMed1986

Reversible renal failure after combined treatment with enalapril and frusemide in a patient with congestive heart failure.

A patient with congestive heart failure and moderate renal insufficiency developed severe reversible non-oliguric renal failure while on frusemide and enalapril. Renal failure developed when enalapril was given in the presence of pronounced sodium depletion. When positive sodium balance was restored the plasma creatinine concentration began to fall while angiotensin converting enzyme inhibition remained effective and blood pressure was stable. These observations suggest that the degree of sodium depletion plays an important role in the tendency for angiotensin converting enzyme inhibitors to induce renal failure in patients with congestive heart failure and moderate renal insufficiency. Restoration of a positive sodium balance promotes the recovery of renal function after the combined administration of angiotensin converting enzyme inhibitors and diuretics.

Acute Kidney Injury↗
PubMed1986

[Clinical pharmacology of enalapril in hypertension with chronic renal failure].

The effects of a single oral dose of enalapril (20 mg) on blood pressure (BP), heart rate (HR) plasma renin activity (PRA) aldosterone (PA), converting enzyme inhibition (CEI) and enalaprilat (E, active metabolite) were investigated during 96 h in 3 groups of 5 hypertensive patients with (1) normal renal function (creatinine clearance: Clcr greater than 80 ml.min-1); (2) moderate chronic renal failure: 80 greater than or equal to Clcr greater than 30 ml.min-1; (3) severe chronic renal failure: 30 greater than or equal to Clcr greater than 10 ml.min-1. Results are as follows (mean +/- SEM): (Table: see text) CEmax: maximal plasma concentration; TEmax: delay corresponding to CEmax; TE 1/2: plasma elimination half-life; AUCE: area under plasma level versus time curve. a: p less than 0.01; b: p less than 0.001; versus (1). In the 3 groups, CEI reached 87-94% as early as the 3rd h; however, at 96 h, CE1 was higher in (3) than in (1) and (2): 77.6 +/- 3.3% versus 6.0 +/- 1.6 and 17.7 +/- 4.8 (p less than 0.001 respectively). In (3). PRA increased at the 1st h and remained elevated: at 96 h, delta PRA was + 3.0 +/- 2.9 ng.ml-1 -.h-1 in (3) versus + 0.10 +/- 0.06 and + 0.25 +/- 0.17 ng.ml-1.h-1 .n (1) and (2) [(3) versus (1): p less than 0.01]; delta PA was lower in (3): -4.56 +/- 2.01 ng. 100 ml-1 versus -0.54 +/- 0.31 and -2.50 +/- 0.38 ng. 100 ml-1 [(3) versus (1): p less than 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1986

[Quality assurance of clinical trials].

A quality assurance system for clinical trials entails the definition, prior to the trial, of a number of procedures (the "good clinical practices") ensuring that it will be correctly conducted and the verification that these procedures have been respected. Setting up a clinical trial quality assurance system involving the manufacturer, university staff and public authorities should result in trials that are better performed. The role and responsibilities of each party are discussed, together with the consequences to be expected from the introduction of good clinical practices in France.

Clinical Trials as Topic↗
PubMed1985

[Treatment of arterial hypertension in the aged subject with a converting enzyme inhibitor: enalapril].

The purpose of this study was to investigate the effectiveness and safety of enalapril in elderly people. A double-blind, randomized, placebo-controlled trial was carried out in 32 subjects aged from 75 to 97 years (mean: 86 years) with blood pressure values equal or superior to 160/90 mmHg. After 8 weeks of treatment with enalapril in doses of 20 to 40 mg/day, the systolic pressure was lowered from 190 +/- 16 to 151 +/- 19 mmHg (P less than 0.0001) and the diastolic pressure from 102 +/- 7 to 85 +/- 11 mmHg (P less than 0.0001). Systolic and diastolic pressures were also significantly reduced in subjects under placebo (from 183 +/- 16 to 165 +/- 21 mmHg, P less than 0.001; and from 101 +/- 9 to 91 +/- 13 mmHg, P less than 0.001, respectively), but the degree of reduction was significantly superior with enalapril (systolic: 39 +/- 25 vs 18 +/- 19 mmHg, P less than 0.005; diastolic: 17 +/- 13 vs 11 +/- 12, P less than 0.001); blood pressure was inferior to 160/90 mmHg in 67% of the subjects treated, as against 35% of those under placebo. Two patients under enalapril died: one on the 27th, the other on the 47th day of treatment. No relation could be established between these deaths and the drug, and this figure of 2 is not significantly different for the number of deaths expected over the same period in a population of that age-group. Among the patients under placebo, one had pulmonary embolism on the 34th day and another had a sudden increase in blood pressure on the 6th day, requiring discontinuation of treatment. It is concluded that enalapril administered alone is effective and well tolerated. Long-term studies are needed to find out whether this angiotensin-converting enzyme inhibitor is superior to a diuretic as initial treatment of arterial hypertension.

Acute Kidney Injury↗
PubMed1983

Acute antihypertensive effect and pharmacokinetics of a tablet preparation of nifedipine.

A tablet formulation of nifedipine was given to 8 hospitalized hypertensive men, W.H.O. stage I or II, mean age 45 years. After an initial placebo test, nifedipine 20, 40 or 60 mg was given in random order at 72-h intervals, in a single administration crossover study. The placebo and the active drug were given at 8 a.m. Blood pressure and heart rate were measured twice by the same observer, every 20 min from 7 to 8 a.m., and then hourly until 8 p.m., first in recumbency and again after 1 min of standing upright. Plasma nifedipine was assayed in samples taken hourly from 8 a.m. to noon, every 2 h from noon to 8 p.m., and 24 and 48 h after drug administration. All 3 doses significantly lowered blood pressure; the fall during recumbency was significantly larger (-18%) and lasted longer (12 h) after 60 mg than after 20 mg (-11% and 7 h). All 3 doses caused a similar increase in heart rate (+29 to +38%), which reached its maximum after 2 h and lasted for 5 h. The maximum plasma concentration and the area under the plasma concentration--time curve were dose-dependent despite large inter-subject variation. Absorption, bioavailability and elimination were linear between the 20 and 60 mg doses. Plasma nifedipine levels were strongly correlated with the concomitant decrease in mean arterial blood pressure (r = 0.61, p less than 0.001). Four patients experienced mild side effects (headaches, flushes, drowsiness or weakness). This tablet form of nifedipine has a potent antihypertensive action which lasts longer than that of the capsule presentation.

Adult↗
PubMed1981

Biochemical tests for diagnosis of phaeochromocytoma: urinary versus plasma determinations.

Fifteen patients with hypertension due to phaeochromocytoma and 35 controls with essential hypertension were studied to assess the diagnostic value of urinary and plasma biochemical determinations in phaeochromocytoma. In every case of phaeochromocytoma the urinary concentration of vanillylmandelate, metanephrines, or adrenaline plus noradrenaline was diagnostic of the disease irrespective of whether the patient was normotensive or hypertensive at the time. Plasma determinations of adrenaline and noradrenaline, however, gave falsely negative results on three occasions. These findings suggest that urinary biochemical determinations--particularly of metanephrines--are more reliable than plasma catecholamine measurements as a test for phaeochromocytoma. The test is particularly useful in patients with intermittent hypertension.

Adrenal Gland Neoplasms↗
PubMed1980

Influence of beta-adrenoceptor blocking agents on the turnover rate of cardiac and splenic noradrenaline in rats.

1 The effects of (+) and (+/-)-propranolol, pindolol, alprenolol, practolol, acebutolol and bretylium were studied on the turnover rate of noradrenaline in heart and spleen of rats. 2 Bretylium (8 mg/kg) greatly reduced the turnover rate of noradrenaline in both organs. 3 (+)-Propranolol (4 and 10 mg/kg) also diminished the turnover rate of noradrenaline, but its effects were smaller than those of (+/-)-propranolol (4 and 10 mg/kg). 4 Pindolol (300 micrograms/kg) greatly increased the turnover rate of noradrenaline; this effect was especially important in the spleen. 5 Alprenolol (4 and 10 mg/kg) acebutolol (20 and 40 mg/kg) practolol (10 mg/kg) did not produce any significant change. 6 These effects are compatible with the view that beta-adrenoceptor blocking agents may affect noradrenaline release in different manners: anaesthetic properties of some of these drugs and blockade of beta 2 prejunctional adrenoceptors produce a diminished release of transmitter, whereas the intrinsic sympathomimetic action of pindolol causes the opposite effect.

Adrenergic beta-Antagonists↗
PubMed1980

Relationship between renin and extracellular fluid volume in normotensive and hypertensive subjects.

Plasma renin activity and extracellular fluid volume were determined in 34 normotensive and in 35 sustained essential hypertensive patients with normal renal function, balanced sodium intake and urinary output. In normotensives, plasma renin activity was negatively correlated to extracellular fluid volume (r = 0.54; p = 0.001). The 95% confidence limits of the normotensive curve was used as nomogram to classify the hypertensive patients into two groups: those (23 cases) that fell within the limits of the normal curve (group I) and those (12 cases) that were below these limits (group II). In comparison with group I, group II was characterized by: (i) similar values for age, blood pressure, inulin clearance and extracellular fluid volume and (ii) significantly but lower values (p less than 0.001) for plasma renin activity with maintenance of the relationship between extracellular fluid volume and renin. The study strongly suggests that (i) the hypertensives of group I had no abnormal regulation of the renin-angiotensin system in comparison with the control subjects and (ii) the hypertensives of group II had an extracellular fluid volume-renin relationship set for lower values of renin.

Adult↗
PubMed1979

Relation of the centrally evoked pressor effect of angiotensin II to central noradrenaline in the rabbit.

Experiments were performed in urethane-anaesthetized rabbits using ventriculo-cisternol perfusion. Central infusion of angiotensin II (50 ng/kg/min) induced a rise in blood pressure which was accompanied by an increase in the noradrenaline concentration of the cerebrospinal fluid. Both effects were highly correlated. Conversely, an i.v. infusion of noradrenaline (5 micrograms/kg/min) which caused a similar increase in arterial pressure did not affect the cerebrospinal fluid catecholamine levels. These results suggest that peripheral cardiovascular effects of centrally administered angiotensin II are related to the activation of noradrenaline structures in the brain.

Angiotensin II↗
PubMed1979

Extracellular fluid volume and renal indices in essential hypertension.

Extracellular fluid volume (EFV), total blood volume (TBV), and renal indices were determined in 53 permanent essential hypertensive patients with normal renal function and balanced sodium intake and urinary output. In comparison with normal subjects, hypertensives had normal EFV values while TBV and the TBV/EFV ratio were significantly reduced (p less than 0.001). In hypertensives, a significant negative relationship (r = -0.40; p less than 0.005) was observed between the TBV/EFV ratio and diastolic arterial pressure. No correlation existed between TBV and diastolic pressure, whereas EFV (and also interstitial fluid volume) was positively related to diastolic arterial pressure (r = +0.41; p less than 0.005). Extracellular fluid volume and interstitial fluid volume were both directly correlated to the renal filtration fraction (r = +0.45; p less than 0.005). The study suggests that, in the disturbed partition of the extracellular fluid of hypertensives, changes in the interstitial space are involved and are related to variations in the renal indices.

Adult↗
PubMed1978

New electron-capture gas-liquid chromatographic method for the determination of mexiletine plasma levels in man.

A method for the determination of mexiletine in human plasma by gas-liquid chromatography with electron-capture detection is described. Plasma samples are extracted at pH 12 with dichloromethane after addition of the internal standard, the 2,4-methyl analogue of mexiletine. A derivative is obtained using heptafluorobutyric anhydride; according to gas chromatography-mass spectrometry it is a monoheptafluorobutyryl compound. The minimum detectable amount of mexiletine is 5 pg. Accurate determinations of human plasma levels were performed after oral or intravenous treatment.

Administration, Oral↗
PubMed1978

Mechanism of inhibition of renin release by clonidine in rats.

In anaesthetized rats, the intracisternal injection of clonidine (1 microgram/kg) reduced mean arterial pressure (MAP), increased plasma renin concentration (PRC) while naphazoline (5 microgram/kg) was ineffective. The i.v. administration of clonidine (30 microgram/kg) still lowered MAP, but in this case, the drug decrease PRC, naphazoline (45 microgram/kg, i.v.) also reduced PRC. It is suggested that i.v. clonidine and naphazoline reduce renin release through activation of alpha-adrenoceptors within the kidney.

Animals↗