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Biomedical subjects

A Richens

Publications and source records attributed to A Richens.

At least 145 records · Page 8Linked to original sources

Determination of smooth pursuit eye movement velocity in humans by computer.

Smooth pursuit eye movements are the output of a system closely related to visual suppression of the vestibulo-ocular reflex, and impairment of these functions when performing day-to-day activities may be important. Smooth pursuit velocity has been assessed using a computerized electro-oculographic technique based on the amount of saccadic activity detected throughout a range of visual target velocities spanning the capability of the smooth pursuit system. Each test session lasts 2 min. With this technique the effects on smooth pursuit of various centrally acting compounds have been demonstrated in healthy subjects. Healthy females had lower smooth pursuit velocities when compared to age-matched males. A linear correlation was shown between smooth pursuit velocity determined by the computer technique and by a previously reported visual method. Such measures have wide application in neurological diagnosis and in the assessment of the central effects of drugs in man.

Computers↗

Bioavailability of diazepam after intravenous, oral and rectal administration in adult epileptic patients.

1 The absorption of single doses of diazepam in six adult epileptic subjects following intravenous, oral and rectal administration were studied in order to evaluate the usefulness of the latter in emergency situations in the adult. 2 Diazepam tablets (Valium, Roche) and rectal solution (Valium solution for intravenous administration) produced similar peak serum concentrations after delays of 15-90 min. 3 Two suppository formulations showed statistically significant differences in absorption characteristics. 4 Serum diazepam levels above 400 ng ml-1 (suggested to be necessary for a satisfactory anticonvulsant effect) were reached in only a few subjects after rectal doses of 10-20 mg of solution, and then usually after a delay of over 2 h.

Administration, Oral↗

Serum protein binding and free concentration of phenytoin and phenobarbitone in pregnancy.

1 The effect of pregnancy on the binding of phenytoin and phenobarbitone to serum proteins was studied in normal women and in drug treated epileptic women. 2 The binding of both drugs was reduced during pregnancy. The reduction correlated positively with the gestational age and negatively with the serum albumin concentration. 3 In spite of the increase in unbound fraction, both the total and free serum concentrations of phenytoin were decreased in late pregnancy.

Adult↗

Valproic acid and diazepam interaction in vivo.

1 The effect of oral administration of sodium valproate (1500 mg daily) on the distribution and elimination kinetics of intravenously administered diazepam in six healthy volunteers has been studied. 2 During valproate administration the unbound fraction of diazepam in serum increased approximately two fold. This was accompanied by a significant increase in apparent volume of distribution and plasma clearance of diazepam. 3 There was a positive correlation between the change in free fraction and the increase in both apparent volume of distribution and plasma clearance of the drug. 4 The concentration of unbound diazepam in serum (calculated from the percent free diazepam and total serum concentration) was significantly higher during valproate administration. Both the intrinsic clearance and volume of distribution of unbound drug were significantly reduced. 5 Mean serum N-desmethyldiazepam levels were significantly lower during valproate coadministration. 6 These results suggest that valproic acid displaces diazepam from plasma protein binding sites and inhibits its metabolism.

Adult↗

Serum protein binding of diazepam in maternal and foetal serum during pregnancy.

1 The serum binding capacity for diazepam was significantly lower in pregnancy and there was a linear correlation with gestational age. 2 The binding of diazepam was not correlated to albumin during pregnancy. 3 In cord sera there was a significantly reduced binding capacity for diazepam with albumin levels of less than 40 g/l.

Blood Proteins↗

Pharmacokinetics of phenylethylmalonamide (PEMA) in normal subjects and in patients treated with antiepileptic drugs.

The pharmacokinetics of phenylethylmalonamide (PEMA), a major metabolite of primidone, were investigated following administration of single oral doses (400 mg) to six normal subjects and six patients receiving chronic treatment with antiepileptic drugs. Peak serum PEMA levels were usually attained with 2-4 h after intake. The oral bioavailability estimated on the basis of the recovery of unchanged drug in the urine of normal subjects was at least 80%. Half-life values ranged from 17 to 25 h in normal subjects and from 10 to 23 h in the patients. No statistically significant difference in any of the calculated kinetic parameters could be found between the two groups. The data indicate that PEMA is readily absorbed from the gastrointestinal tract and that it is eliminated predominantly unchanged in the urine of man.

Adult↗

Absorption of diazepam from the rectum and its effect on interictal spikes in the EEG.

Rectal administration of several different preparations of diazepam to a group of adult volunteer patients with epilepsy produced variable rates of absorption. Peak serum concentrations following 10 mg, 20 mg, and 30 mg of diazepam solution were achieved between 13-60 min, 10-120 min, and 30-90 min respectively. An experimental diazepam "solid solution" suppository was found to have significantly better absorption characteristics compared with the commercially available Valium suppository. Diazepam solution 20 mg was administered rectally in 10 adult epileptic patients with frequent spontaneous interictal spikes in their EEGs. A highly significant reduction in spike frequency was seen compared with placebo. The effect was most marked 10-20 min after administration of diazepam, when the mean spike count fell to 39 +/- 35 SD percent of the control value (p less than 0.01), and this corresponded with a mean serum diazepam level of 210 +2- 125 ng/ml.

Adolescent↗

Rectal absorption of diazepam in epileptic children.

The absorption of diazepam after rectal administration was studied in children with epilepsy. When given as a solution, diazepam was rapidly absorbed and produced serum diazepam concentrations above 200 ng/ml within 10 minutes in most children. However, a commercial suppository formulation was absorbed slowly and cannot be recommended for urgent treatment of fits. There is a need in the UK for a rapidly absorbed preparation of diazepam which is approved for rectal use.

Adolescent↗

Controlled study of metoprolol and propranolol during prolonged administration in patients with essential tremor.

The efficacy of propranolol and metoprolol in the treatment of essential tremor was compared in a double blind crossover placebo-controlled study in 16 patients. Each treatment was given for a period of 4 weeks at two different dosage regimens (150 and 300 mg daily for metoprolol, 120 and 240 mg daily for propranolol). Each dosage regimen lasted for 2 weeks. Tremor assessment was carried out by accelerometry, clinical evaluation, patient's self-rating and a battery of performance tests. At the lower dosage, propranolol was found to be superior to placebo on the basis of performance tests and patient's self-assessment. At the higher dosage, propranolol was superior to placebo on all methods of assessment. By contrast, the tremorolytic effect of metoprolol was not significantly different from that of placebo, irrespective of the dosage or of the method of assessment used. Propranolol (120 mg daily) was better than metoprolol (150 mg daily) on the basis of clinical evaluation and patient's self-assessment. Propranolol (240 mg daily) was superior to metoprolol (300 mg daily) on the basis of patient's self-assessment. Both drugs antagonised standing tachycardia to a similar extent. These results indicate that the effectiveness of metoprolol, previously demonstrated in a single-dose study in the same patients, is not fully maintained during prolonged administration. In the absence of specific contraindications, propranolol represents a better choice in the treatment of patients with essential tremor.

Adult↗

An efficient technique for determining characteristics of saccadic eye movements using a mini computer.

A new technique has been developed to quantify objectively certain characteristics of saccadic eye movements which can be used as indices of the effect of centrally-acting compounds. During a three minute test session subjects sit with their heads in a fixed position and are asked to follow horizontal step displacements of a spot on a CRT screen, driven by signals previously recorded on FM analogue tape. Displacements of the spot are produced at random intervals which result in saccadic eye movements having amplitudes 10 degrees to 40 degrees. The corneo-retinal potentials are d.c. amplified and stored on the same on the same tape, later sampled at 256 Hz, filtered, differentiated and compared to the spot-displacement signal. Reaction time, duration, peak velocity, post saccadic interval and saccadic accuracy are then determined. Efficient use of computer resources has been achieved with improvements in control of experimental conditions, in reliability and in accuracy of measurements. Automatic unbiased rejection of erroneous data has been achieved. The efficiency of the technique has made extensive clinical trials possible in an environment where computer power is not devoted to eye movement-measurements. In confirmation of previous work the peak velocity characteristic has been identified as a sensitive measure of the effect of several benzodiazepines.

Action Potentials↗

Propranolol and sotalol as antagonists of isoproterenol-enhanced physiologic tremor.

Six normal subjects were studied after graded bolus injections of isoproterenol. Log dose-response curves for increases in both heart rate (mostly beta 1), and amplitude of physiologic tremor (beta 2) were constructed for each subject in the control state and 2 hr after 10 or 40 mg propranolol, 200 mg sotalol, or placebo. All heart rate curves were shifted to the right in an approximately parallel fashion by all active treatments (40 mg propranolol greater than 200 mg sotalol greater than 10 mg propranolol). The tremor curve was also shifted to the right by 10 mg propranolol in an approximately parallel fashion and to the same extent as the heart rate curve (both dose-ratios = 6.1), but the tremor curves after both 40 mg propranolol and 200 mg sotalol appeared to be flattened as well as shifted laterally. We conclude that whereas it may be possible that 10 mg propranolol acts as a competitive antagonist of isoproterenol at beta 2-sites in skeletal muscle, 40 mg propranolol and 200 mg sotalol must have additional actions in reducing isoproterenol tremor. The possibilities are discussed.

Administration, Oral↗

Effect of atenolol, metoprolol, and propranolol on isoproterenol-induced tremor and tachycardia in normal subjects.

The effect of single oral doses of atenolol (100 mg), metoprolol (100 mg), propranolol (40 mg), and placebo on exercise tachycardia and on heart rate and finger tremor responses to graded injections of isoproterenol was investigated in six normal subjects. Propranolol was more potent than atenolol and metoprolol in suppressing the increase in heart rate and tremor amplitude produced by isoproterenol, even though at the dose used it was the least effective of all three drugs in decreasing exercise tachycardia. Although these data are consistent with the hypothesis that the suppression of isoproterenol-induced tremor is mediated by antagonism of peripheral beta 2-adrenergic receptors, the possibility that a separate action other than beta-blockade may contribute to the tremorolytic action of propranolol cannot be excluded. The potential usefulness of examining the effect of beta-adrenoceptor blocking drugs on isoproterenol-induced tremor and tachycardia in cardioselectivity studies is discussed.

Adult↗