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Biomedical subjects

M D Drici

Publications and source records attributed to M D Drici.

33 records · Page 2Linked to original sources
PubMed1993

Prevalence of toxoplasma myocarditis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To evaluate the prevalence of cardiac toxoplasmosis in a series of 182 necropsies performed between 1987 and 1991 on patients infected with the human immunodeficiency virus (HIV), to correlate this prevalence with the ante mortem diagnosis of cardiac involvement, and to assess the role of such cardiac lesions in the immediate cause of death. PATIENTS AND METHODS: Complete necropsies of 182 HIV-infected patients (48 women, 134 men) were performed consecutively between 1987 and 1991. Risk factors, identified in 174 cases, included drug abuse (111/182), homosexuality (51/182), and blood transfusions (12/182). 16 samples were systematically obtained from each heart for histological study. If trophozoites or lymphocytic myocarditis were seen, immunohistochemical investigations were carried out with polyclonal antibodies for Toxoplasma gondii. An ultrastructural study was performed in four patients with toxoplasma myocarditis. Myocardial lesions were defined by the Dallas classification. Clinical data (and information on electrocardiograms and echocardiograms) were obtained from medical records. RESULTS: Cardiac toxoplasmosis was diagnosed at necropsy in 21 (12%) patients. Cardiac lesions were associated with toxoplasmic encephalitis in 18 patients and were solitary in three patients. Acute diffuse myocarditis was present in 6/21, rare foci of myocarditis were seen in 8/21, and intramyocytic toxoplasmic cysts without any inflammatory reaction or necrosis were seen in 4/21. Anti-toxoplasma immunolabelling showed cardiac toxoplasmosis in three patients with lymphocytic myocarditis. Particles with the ultrastructural characteristics of Toxoplasma gondii trophozoites were seen in four cases. Six patients had presented with cardiac symptoms, confirmed by electrocardiographic and echocardiographic abnormalities during their disease course, and their cardiac lesions were directly responsible for the death. CONCLUSION: Cardiac toxoplasmosis was common in this necropsy series of HIV-infected patients. Cardiac toxoplasmosis had been suspected clinically in four patients. Myocardial lesions were generally asymptomatic and were not discovered until necropsy. Solitary cardiac involvement was not uncommon reflecting parasite reactivation at a myocardial site. The incidence of cardiac toxoplasmosis in this group of immunodepressed subjects from an area with a high prevalence of this parasitic disease justifies regular follow up of such patients by electrocardiography and echocardiography as well as immediate administration of anti-toxoplasma treatment should sudden heart failure occur.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Is verapamil also a non-selective beta blocker?

Verapamil is a calcium channel blocker widely used as an antihypertensive agent, and its pharmacological effects may partly be due to some degree of beta blockade. In order to evaluate the changes occurring in beta-2 adrenoceptor density, 40 patients with mild to moderate hypertension received verapamil 240 mg (once a day) or captopril 20 mg (twice a day) during 30 days, in a double-blind randomized study, after a placebo run-in period. The lymphocytic membrane beta-2 adrenoceptor density (Bmax) was determined before the administration of active drugs and after a 15-day treatment. After a month of treatment, most patients showed a marked reduction of their diastolic blood pressure: from 98.2 +/- 3.2 mmHg to 81.2 +/- 4.0 mmHg (p < 0.05), in the verapamil group, and from 95.0 +/- 6.0 mmHg to 82.5 +/- 4.8 mmHg (p < 0.05) in the captopril group. After 15 days of treatment, verapamil induced an up-regulation of beta-2 adrenoceptors from 39.5 +/- 8.3 fmol/mg protein to 58.5 +/- 12.0 fmol/mg protein (p < 0.05), whereas the Bmax in the captopril group did not significantly change. No significant change occurred in the two dissociation constants. This up-regulation phenomenon, common among beta-2 blockers, supports the hypothesis of verapamil's beta blockade potency.

Adrenergic beta-Antagonists↗
PubMed1992

[Evaluation of anti-atheromatous properties of calcium channel inhibitors].

Calcium is involved in several biochemical atherogenesis processes and its activity is antagonised in cell and animal experimental models by all classes of slow channel calcium inhibitors. However, the doses required in animals to slow the development of atherosclerotic lesions are above therapeutically acceptable doses in man. The clinical relevance of their anti-atherosclerotic activity in the few clinical studies undertaken is difficult to assess because of the variable criteria of judgment used.

Animals↗
PubMed1992

Placebo effect in cardiovascular clinical pharmacology.

A placebo is a pharmacologically inactive substance that can have a therapeutic effect if administered to a patient who believes that he or she is receiving an effective treatment. It is generally admitted that the placebo effect decreases blood pressure in 20% to 30%, when evaluated by casual sphygmomanometer or ambulatory systems. In order to evaluate the occurrence of a placebo effect in cardiovascular pharmacology, we analysed two studies. One study included ten mild-to-moderate hypertensive patients, and consisted of two submaximal exercise tests separated by a single oral administration of the placebo. The other study included six healthy volunteers, receiving an oral placebo during ten days. The placebo was in both case presented as an effective antihypertensive agent. Any change on blood pressure and heart rate, both at rest and during exercise, was observed before and three hours after the placebo. After ten days of placebo administration, no statistically significant change in blood pressure or heart rate was obtained. Nor was any statistical difference observed in catecholamine plasma levels, either three hours or ten days after oral administration of the placebo. The second study did not show any evidence of changes in lymphocytic beta-adrenoceptor density after ten days of placebo. The results of these pilot studies suggest that the use of a placebo group in cardiovascular clinical pharmacology should be reconsidered. The real occurrence and characteristics of a placebo effect should be evaluated by a complementary study.

Blood Pressure↗
PubMed1991

Influence of beta-blockade on circulating plasma levels of 3-methoxy-4-hydroxy phenylethylene glycol (MHPG) during exercise in moderate hypertension.

1. The effect of exercise testing and beta-blockade on plasma norepinephrine (PNE), and secretion of its metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), was assessed in 28 mild-to-moderate hypertensives before and after the administration of dilevalol, a new beta-blocker with beta 2-agonism. 2. This double blind, placebo-controlled study consisted of two successive submaximal exercise tests before and after the administration of a single oral dose of dilevalol (200 mg, 400 mg or 600 mg). Plasma norepinephrine levels were determined at rest, at 100 watts step of exercise and at maximal effort (Emax). 3. During the control test, mean PNE levels increased from 1.73 +/- 0.52 nmol/L (resting value) to 8.01 +/- 4.01 nmol/L at Emax (P less than 0.01) as MHPG levels increased from 11.18 +/- 1.33 nmol/L (rest) to 17.50 +/- 1.15 nmol/L (Emax, P less than 0.01). After dilevalol, PNE increased significantly as compared to controls (P less than 0.05), from 2.32 +/- 0.99 to 12.42 +/- 5.97 nmol/L (P less than 0.01). PNE and MHPG levels were correlated, both at rest and during exercise. PNE levels after beta-blockade were linearly related to the dose of beta-blocker administered. MHPG levels were unaltered by the administration of dilevalol, both before and after exercise. 4. The increase in MHPG that occurs during bicycle exercise is largely generated from an increase in central nervous system noradrenergic activity. While dilevalol increases the peripheral sympathetic nervous system, both at rest and during exercise (which is reflected by increases in PNE levels) the drug does not alter resting central nervous system noradrenergic activity nor amplify the increase in central noradrenergic activity that occurs during exercise.

Adrenergic beta-Antagonists↗
PubMed1991

[Comparative efficacy of sustained release verapamil and captopril in mild to moderate arterial hypertension by ambulatory measurement and occasional measurement].

The evaluation of mild to moderate hypertension must be carried out under the conditions in which treatments are usually prescribed, i.e., in general practice. After specific training of the physicians in the methods used, we evaluated the efficacy and safety of a new formulation of verapamil by comparing it with a reference drug: captopril. The main assessment criterion was the restoration of normal blood pressure in mildly to moderately hypertensive patients (blood pressure in excess of 160/95 mmHg). Blood pressure was evaluated by two methods: a mercury column sphygmomanometer, after the patient had rested in a half-sitting position for 10 minutes, and the ambulatory measurement of blood pressure (AMBP) using the SpaceLabs system. The results of this study involving 40 patients followed up for 3 months by 8 GPs in collaboration with our blood pressure unit were as follows: on verapamil, 47% of patients recovered normal values after 30 days of treatment and 71% after 60 days (with no change in dosage). On captopril, the normalization rates were 22 and 27% respectively. The highly significant reduction of blood pressure found by the "occasional" measurement for both treatments (p less than 0.001) was only faintly reflected by AMBP. Verapamil induced a reduction of nighttime blood pressure with no significant impact on heart rate. The clinical, paraclinical and electrocardiographic safety of both treatments was good.

Adult↗
PubMed1991

Clinical and biological evaluation of dilevalol vasodilating properties in mild to moderate hypertension.

Dilevalol is a vasodilating beta-blocker with proven antihypertensive activity. In this study, 28 patients with mild-to-moderate uncomplicated hypertension underwent 2 submaximal exercise tests, each consisting of progressive steps of 20 watts for 2 minutes or up to 85% theoretical maximum heart rate. Five minutes after the first test, patients received either placebo or dilevalol 200 mg, 400 mg or 600 mg. The second exercise test was performed 3 hours later. Diastolic blood pressure, systolic blood pressure, heart rate and norepinephrine plasma levels were assessed before and after exercise. Dilevalol at all doses caused a significant decrease in heart rate and blood pressure both at rest and during exercise, compared to placebo. Dilevalol 600 mg had a greater effect on diastolic blood pressure than dilevalol 200 mg and 400 mg. Administration of dilevalol 200 mg and 400 mg enabled 42% of patients to increase their maximal exercise level by 20 to 60 watts. Dilevalol increased plasma norepinephrine levels at the 100 watts exercise levels from 5.1 +/- 4.0 nmol/l to 7.6 +/- 4.3 nmol/l (p less than 0.05). No adverse effects were observed during dilevalol treatment. This study shows that dilevalol is an effective antihypertensive agent that blunts heart rate and blood pressure risings during exercise.

Administration, Oral↗
PubMed1991

Lack of placebo effect in exercise response of hypertensive patients.

UNLABELLED: The administration of placebo (a pharmacologically inactive substance) is justified in clinical trials of antihypertensive drugs in order to exclude the placebo effect. The evaluation of antihypertensive treatments during exercise is an interesting end point, since aerobic exercise is part of antihypertensive treatment. The aim of this study is to determine the placebo effect on blood pressure, heart rate and catecholamine secretion profiles during exercise testing. METHOD: 10 patients with untreated mild to moderate essential hypertension participated in a single blind study consisting of two successive submaximal exercise tests (85% of maximal predicted heart rate), separated by a single oral administration of placebo. Blood pressure and heart rate were measured after 10 minutes of rest and at the end of each effort step (2 min, 20 Watts), both before and after placebo. Blood samples (5 ml) were collected at rest and during maximal exercise before and after placebo, in order to determine the effect of placebo on circulating catecholamines. RESULTS: There were no significant difference between the "control" and after placebo exercise tests, neither in blood pressure or heart rate profiles, nor in values of circulating catecholamines (noradrenaline at rest: 1.88 +/- 0.96, effort: 6.43 +/- 1.93 nm/l before placebo, 1.65 +/- 0.83 nm/l and 5.71 +/- 2.12 nm/l after placebo respectively [NS]). CONCLUSION: The placebo effect, which is generally determined from blood pressure at rest by sphygmomanometry, seems devoid of any influence on blood pressure, heart rate or catecholamine profiles during exercise in patients with mild to moderate essential hypertension. Thus, antihypertensive treatments can be evaluated during exercise by comparison to baseline cardiovascular parameters without need of a placebo group.

Adult↗
PubMed1990

[Alpha-1 inhibition and blood pressure regulation].

The Alpress LP osmotic tablet enables progressive and prolonged release of prazosin into the digestive tract over a 16 hour period. This leads to the maintenance of stable plasma concentrations of the drug and the absence of high plasma peaks during the absorption of prazosin. The antihypertensive effect prazosin persists throughout the day and night, ensuring effective blood pressure regulation and treatment is well tolerated by patients.

Adrenergic alpha-Antagonists↗
PubMed1990

[Evaluation of the placebo effect on blood pressure profile during exercise in patients with mild uncomplicated hypertension].

UNLABELLED: The administration of placebo (pharmacologically inactive substance) is justified in clinical trials of antihypertensive drugs, in order to avoid the inclusion of placebo-responders. The evaluation of antihypertensive treatments during exercise is an interesting end point, since aerobic exercising is part of antihypertensive treatment. The aims of this study are to determine the placebo impact on blood pressure, heart rate and catecholamine secretion profiles during exercise testing. METHOD: 10 untreated essential mild to moderate hypertensives participated to a single blind study comprising two successive submaximal exercise testings (85% of maximal theoretical heart rate), separated by a single oral administration of placebo. Blood pressure and heart rate were measured after 10 minutes of resting position and at the end of each effort step (2 mm, 20 Watts), both before and after placebo. Blood samples (5 ml) were collected at rest and during maximal exercise before and after placebo, in order to determine the effect of placebo on circulating catecholamines. RESULTS: there was no significant variations between the "control" and exercise testings after placebo, neither on blood pressure or heart rate profiles, nor in values of circulating catecholamines [Noradrenaline at rest: 1.88 +/- 0.96, exercise: 6.43 +/- 1.93 nm/l before placebo, 1.65 +/- 0.83 nm/l and 5.71 +/- 2.12 nm/l after placebo respectively (NS)]. CONCLUSION: the placebo, which effect is generally determined on blood pressure at rest by sphygmomanometry, seems devoid of any activity on blood pressure, heart rate or catecholamine profile during exercise, in essential moderate hypertensives. Thus, antihypertensive treatments at exercise can be evaluated by comparison to baseline cardiovascular parameters without placebo groups.

Adult↗
PubMedDate not supplied

Cardiac K+ channels and drug-acquired long QT syndrome.

The hallmark of long QT syndromes (LQTS) is an abnormal ventricular repolarization characterized by a prolonged QT interval on the electrocardiogram and a propensity to the occurrence of syncopes resulting from polymorphic ventricular tachycardia, called torsades de pointes. They may degenerate to ventricular fibrillation, possibly causing sudden death. Congenital LQTS, which implicates at least six chromosomal loci, LQT1 to LQT6, three of them corresponding to mutations concerning the coding of K+ channel proteins, give useful information about the mechanism underlying the arrhythmia. One of the potassium channel genes implicated in congenital LQTS is HERG, which encodes the IKr current channel protein. This current has provided a relevant insight into the occurrence of drug-acquired LQTS, since all drugs associated with torsades, such as erythromycin, terfenadine, haloperidol, or cisapride, also block IKr.

Heart↗
PubMedDate not supplied

Effects of calcium channel blockers on cloned cardiac K+ channels IKr and IKs.

Cloned HERG and KvLQT1-IsK K+ channels have been expressed in mammalian cells and assayed as a target for calcium channel blockers. These channels generate the rapid and slow components of the cardiac delayed rectifier K+ current, and mutations can affect them that lead to long QT syndromes. HERG is blocked by bepridil (EC50 = 0.55 microM), verapamil (EC50 = 0.83 microM) and mibefradil (EC50 = 1.43 microM), whereas nitrendipine and diltiazem have negligible effects. Steady-state activation and inactivation parameters are shifted to more negative values in the presence of the blockers. Similarly, KvLQT1-IsK is inhibited by bepridil (EC50 = 10.0 microM) and mibefradil (EC50 = 11.8 microM), whilst being insensitive to nitrendipine, diltiazem or verapamil. This work may help to understand the mechanisms of action of verapamil in certain ventricular tachycardias as well as some of the deleterious adverse cardiac events associated with bepridil and mibefradil.

Animals↗