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Biomedical subjects

M D Rawlins

Publications and source records attributed to M D Rawlins.

At least 163 records · Page 9Linked to original sources
PubMed1982

A comparison of phenytoin and valproate in previously untreated adult epileptic patients.

Eighty-eight patients with the onset of epilepsy in adult life were randomly allocated to treatment with sodium valproate (600 mg/day), or phenytoin (300 mg/day), and followed up for at least 12 months. Both drugs were highly effective in the control of tonic-clonic seizures, irrespective of whether they were accompanied by focal features, but were markedly less effective in the control of partial seizures. Two patients exhibited acute allergic reactions to phenytoin. No significant differences have yet emerged in the efficacy of the two drugs, and valproate may be considered as a "fist-line" anticonvulsant in the treatment of adult onset epilepsy.

Adolescent↗
PubMed1982

N-acetylation phenotype in bladder cancer.

1 N-acetylation phenotype has been examined in 30 patients with bladder cancer and in 27 controls of similar age. 2 59% of controls and 70% of bladder cancer patients were phenotypically 'slow' acetylators. This difference was not significant (P greater than 0.30). 3 Within phenotypes, isoniazed half life was similar in controls and bladder cancer patients. 4 N-acetylation phenotype is unlikely to be a major determinant in the pathogenesis of bladder cancer in the population studied.

Acetylation↗
PubMed1981

Blood concentrations of acetaldehyde during chlorpropamide-alcohol flush.

To test the suggestion that chlorpropamide-alcohol flushing (CPAF) resembles the disulfiram effect and might be mediated by acetaldehyde, the initial metabolite of alcohol, blood concentrations of acetaldehyde were measured after a drink of alcohol in controls and diabetics positive and negative for CPAF. The CPAF-positive diabetics had significantly greater blood acetaldehyde concentrations after alcohol than the CPAF-negative diabetics both with a single dose of chlorpropamide and after two weeks' chlorpropamide treatment. Concentrations in the CPAF-positive group after chlorpropamide were also significantly greater than after a placebo tablet. There was also a clear separation in the increase in facial temperature after two weeks of chlorpropamide between the CPAF-positive and CPAF-negative groups (although there was some overlap after a single tablet). There was no difference in plasma chlorpropamide or alcohol concentrations between CPAF-positive and CPAF-negative diabetics. These findings show that CPAF is distinct from alcohol flushing and that the acetaldehyde concentration in the blood provides an objective measure of CPAF. The difference between flushing and non-flushing diabetics cannot be accounted for by differences in blood concentrations of chlorpropamide or alcohol.

Acetaldehyde↗
PubMed1981

Placebo-controlled study of phenobarbitone and phenytoin in the prophylaxis of febrile convulsions.

Of 138 children who had a first febrile convulsion before their second birthday, 48 were treated with phenobarbitone, 47 with phenytoin, and 43 with a placebo for 12 months. Drug levels were monitored and adverse effects of the drugs were noted. Compared with placebo, phenobarbitone significantly reduced recurrences among children under 14 months old at the time of their first convulsion, but nor among older children. Phenytoin was an ineffective prophylactic agent. Ideal drug levels were difficult to maintain, and many recurrences occurred when concentrations were suboptimal. Behavioural disturbance in children taking phenobarbitone was not a serious problem. The decision to give continuous prophylaxis for febrile convulsions is complex, and each case must be judged on its merits. For children who have a first seizure before 14 months of age prophylaxis may be advisable and phenobarbitone is effective.

Age Factors↗
PubMed1981

Pharmacokinetics of parenteral paracetamol and its analgesic effects in post-operative dental pain.

A double-blind, randomised, crossover trial was undertaken to compare the analgesic effects of a single dose of paracetamol (1000 mg i.v.) with placebo in the immediate post-operative period following removal of impacted lower third molars. There was no significant difference in the pain relief between paracetamol and placebo in the first hour following injection. Thereafter, there was significantly less pain (P less than 0.05) after treatment with paracetamol than after placebo. Plasma concentrations of paracetamol were measured and pharmacokinetic variables were determined. Over the four hour period of investigation there was no clear relationship between analgesia and paracetamol concentration in either central or peripheral compartments.

Acetaminophen↗
PubMed1981

Monitoring of phenobarbitone and phenytoin therapy in small children by salivary samples.

Concentrations of phenytoin or phenobarbitone have been measured serially using saliva samples in 75 very young children receiving one of these drugs for prevention of recurrent febrile convulsions. Saliva samples were easily obtained and the measured concentrations were a valuable guide to drug dosage during the treatment period. Mean (+/- SD) saliva concentrations were, for phenytoin, 1.0 +/- 0.8 mg/litre (3.8 +/- 3.0 mumol/litre) and, for phenobarbitone, 7.9 +/- 2.6 mg/litre (24.0 +/- 11.3 mumol/litre) and did not alter significantly during the period of observation. Despite frequent review with assessment of compliance, it proved difficult to achieve and maintain target drug concentrations. Paired samples of saliva and plasma were obtained from 36 children before treatment was terminated. Drug concentrations in saliva correlated well with those in plasma and mean plasma: saliva ratios (phenytoin, 8.4; phenobarbitone, 2.2) were comparable to results obtained previously in adults.

Dose-Response Relationship, Drug↗
PubMed1981

Epoxide hydrolase activity in human skin.

1 Epoxide hydrolase (EH) activity was measured in biopsied skin (n = 42) using 7-[H3]-styrene oxide as substrate, and separation of the products by high performance liquid chromatography. 2 EH activity (mean +/- s.d.) was present in separated epidermis (139 +/- 105 pmol glycol formed mg-1 min-1) and dermis (165 +/- 120 pmol glycol formed mg-1 microsomal protein min-1). 3 Whole skin EH activity (mean +/- s.d.) varied widely (433 +/- 254 pmol glycol formed mg-1 microsomal protein min-1) 4 No significant difference in EH activity was observed in skin from breast, penis and leg. 5 Skin EH activity does not appear to contribute significantly to the systemic metabolism of epoxide, but may be important in determining the effects of epoxides formed within the epidermis.

Adolescent↗
PubMed1981

Pharmacokinetics of phenytoin in children.

1 Apparent Vmax and Km for phenytoin were estimated in 40 children (aged 8--33 months) and 21 adults (aged 18--66 years). 2 The derived values of Vmax and Km were used to predict the plasma and salivary concentrations of phenytoin following a change in dose. There was a highly significant correlation between observed and predicted steady-state concentration in both children and adults (P less than 0.001). 3 The apparent Km was similar in children (7.5 +/- 1.2 mg/l) and adults (9.4 +/- 2.3 mg/l). 4 Vmax differed significantly (P less than 0.001) between children (20.4 +/- 2.1 mg kg-1 day-1) and adults (8.7 +/- 0.7 mg kg-1 day-1). 5 After correction for differences in the ratio of liver weight to body weight in children and adults, Vmax was similar in the two groups.

Body Weight↗
PubMed1981

Behavioural effects of phenobarbitone and phenytoin in small children.

Mothers of 56 children under 2 years old taking phenobarbitone and mothers of 55 children taking phenytoin recorded on questionnaires changes they had noted in the children's behaviour 3 and 9 weeks after starting the drug. Severe behavioural disturbance was noted by many, but the pattern and incidence was similar to that recorded by the mothers of 50 children starting a placebo, and we attribute it to the effect of a recent hospital admission. There was a small improvement in the behaviour of 20% of children who had been taking phenobarbitone for a year when they stopped it, but in this age group the disturbance caused by phenobarbitone did not appear to have been great.

Child Behavior Disorders↗
PubMed1981

Chronic hypothermia following tuberculous meningitis.

A patient who developed chronic hypothermia following tuberculous meningitis is described. A central defect of thermoregulation was discovered, probably due to a discrete vascular lesion in the anterior hypothalmus.

Adult↗
PubMed1980

Generalised tissue abnormality of aryl hydrocarbon hydroxylase in psoriasis.

Microsomal aryl hydrocarbon hydroxylase (AHH) activity and inducibility were measured in jejunal mucosa, liver, and lesion-free epidermis of patients with psoriasis. In all three tissues AHH activity and inducibility were less than in controls. This demonstration of a generalised enzymatic abnormality in the tissues of patients with psoriasis is in keeping with the suggestion that it may be close to the underlying genetic defect.

Adolescent↗
PubMed1980

The effect of age on the pharmacokinetics of diazepam.

1. After intravenous administration to 19 subjects, aged 18-95 years, plasma diazepam concentrations were measured over 160 h. Plasma protein binding of diazepam was also measured in each subject. 2. The terminal plasma half-life of diazepam ranged from 15.0 to 125 h and was positively correlated with age (r = 0.797). Total plasma diazepam clearance was not correlated with age (r = -0.017). 3. The free fraction of diazepam ranged from 0.0137 to 0.0386 and was significantly correlated with age (r = +0.863). Free diazepam clearance, which ranged from 432 to 1870 ml/min, was also correlated with age (r = -0.717). 4. It is concluded that the increased sensitivity of the elderly to diazepam is, at least in part, due to pharmacokinetic factors.

Adolescent↗