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Biomedical subjects

R A Braithwaite

Publications and source records attributed to R A Braithwaite.

At least 19 recordsLinked to original sources

Induction of DNA strand breaks in peripheral lymphocytes by soluble chromium compounds.

1. Incubation of human lymphocytes with sodium dichromate (CrVI) at 37 degrees C for 3 h resulted in a dose-dependent increase in DNA strand breaks without concurrent cytotoxicity. In contrast, chromium acetate hydroxide (CrIII) failed to induce DNA strand breaks at sub-cytotoxic concentrations. 2. DNA strand breaks were also detected in the peripheral lymphocytes of Wistar rats, 24 h after intratracheal instillation of sodium dichromate (1.3 and 2.5 mg kg-1). Instillation of chromium acetate hydroxide (up to 21.8 mg kg-1) failed to induce DNA strand breaks in peripheral lymphocytes. In accord with previous studies, hexavalent chromium was found to be more readily absorbed from the lungs into the peripheral blood than chromium in its trivalent form. 3. The results of this study indicate that fluorometric analysis of DNA unwinding (FADU) in peripheral lymphocytes might be a convenient method of measuring an important biological effect of chromium in occupationally-exposed workers.

Animals

Disintegration of mercury disc cells in simulated gastric juice: implications for management of disc cell ingestion.

The disintegration of charged alkaline mercury button cells in simulated gastric fluid over a 24 h period has been studied. The integrity of the cells and the amount of mercury that can leak out of them were assessed. The cells raised the pH of the incubating solutions. Disruption was seen in five out of 18 cells tested in 0.1 mol/L hydrochloric acid and one out of nine in 0.9% saline. Five of the six disrupted cells were made by the same manufacturer. Major leakage of mercury only occurred after complete disintegration of the cells. The implications of these findings for the management of patients who have ingested mercury-containing button cells are discussed.

Animals

Simplified method for monitoring tricyclic antidepressant therapy using gas--liquid chromatography with nitrogen detection.

A simplified gas chromatographic method for the rapid measurement of tricyclic antidepressant drugs in plasma using a nitrogen-sensitive detector is described. All drugs are extracted and chromatographed under identical conditions. Tertiary amines are separated from their secondary amine metabolites, which are determined simultaneously without the need for derivatisation. The lower limit of accurate determination for most drugs is 10 microgram/1. The method has been applied to the routine measurement of amitriptyline and nortriptyline in plasma from patients receiving antidepressant treatment. Large and important interindividual differences in plasma concentrations in the patients investigated have been found, and the significance of these results is discussed.

Antidepressive Agents, Tricyclic

Relationship between clinical features of tricyclic antidepressant poisoning and plasma concentrations in children.

Clinical features and drug plasma concentrations were studied in 13 children admitted to hospital with tricyclic antidepressant poisoning. Patients with plasma concentrations below 500 microgram/l had anticholinergic signs and increased reflexes but did not have convulsions or cardiac arrhythmias. Four patients with plasma concentrations above 1000 microgram/l suffered convulsions, cardiac arrhythmias, or prolonged coma. The diagnosis of poisoning in 2 of these cases was made only by toxicological analysis. Quantitative estimation of tricyclic antidepressants is useful in atypical or severe poisoning both to reach the diagnosis and to give an idea of the likely duration of symptoms.

Antidepressive Agents, Tricyclic

Cardiac effects of tricyclic antidepressant medication. A preliminary study of nortriptyline.

Systolic time intervals and drug plasma concentrations have been measured in a group of patients receiving repeated treatment with nortriptyline. Significant positive correlations between plasma nortriptyline levels and prolongation of pre-ejection phase (P less than 0.005)) and increase in the ratio pre-ejection phase, left ventricular ejection time (P less than 0.05) were obtained. A deterioration in cardiac function, with increase in heart rate, resulting in a negative inotropic effect has been shown to occur with therapeutic doses of nortriptyline. The potential dangers of tricyclic antidepressant drugs on the heart in patients whose myocardium is already compromised or those who accumulate high plasma concentrations are emphasised.

Adult

Measurement of plasma nortriptyline concentrations: radioimmunoassay and gas-chromatography compared.

We compared measurement of plasma nortriptyline by a recently developed radioimmunoassay technique with values obtained by traditional gas chromatography. The coefficient of correlation (r) was 0.98 for 84 samples from 21 controlled patients; for a separate series of 45 samples from 34 patients who were receiving in addition other medication, r was 0.96. Use of radioimmunoassay in the routine determination of plasma nortriptyline concentration is discussed.

Chromatography, Gas

Effect of activated charcoal on absorption of nortriptyline.

The ability of 'Medicoal', a new effervescent, activated charcoal preparation, to adsorb nortriptyline, has been investigated both in vitro and in vivo. A single dose of the effervescent charcoal 30 min after a dose of 75 mg nortriptyline produced a 60% mean reduction in both peak plasma levels and nortriptyline availability in healthy volunteers. Multiple doses of the effervescent charcoal produced 70% mean reduction in peak nortriptyline levels and availabiltiy. Activated charcoal is recommended for the treatment of tricyclic antidepressant poisoning. In in-vitro tests, a 10 g packet of the effervescent preparation containing 5 g activated charcoal) had an adsorptive capacity of approximately 3000 mg nortriptyline, a dose not usually exceeded in most cases of trycyclic antidepressant overdose.

Absorption

Experimental drug intoxication: treatment with charcoal haemoperfusion.

Dogs were given large doses of barbiturates, glutethimide, ethanol, methaqualone, ethchlorvynol, meprobamate, chloral hydrate, paracetamol and aspirin. These were treated by haemoperfusion using a column packed with charcoal coated with an acrylic hydrogel. Clearances for most drugs were significantly higher than those reported for haemodialysis. Minimal clearances of common biochemical entities were observed and although leucocyte and platelet counts were diminished, no deleterious effects attributable to this were encountered. Careful histological examination of tissues derived from perfused dogs revealed no evidence of charcoal emboli.

Acetaminophen

In vivo measurements of cadmium and lead in occupationally-exposed workers and an urban population.

This paper reports the preliminary findings of a survey of lead and cadmium body burdens in a nonoccupationally exposed population in Swansea, Wales, using the techniques of in vivo neutron activation and X-ray fluorescence analysis. Some measurements on an occupationally cadmium-exposed group are also included. The results confirm the association between cadmium and smoking and bone lead and age. The in vivo measurements demonstrate a degree of comparability with other data, which supports the further detailed analysis of the relationships between body burden and exposure, on the one hand, and possible health effects on the other.

Adult