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Biomedical subjects

D W Holt

Publications and source records attributed to D W Holt.

At least 145 records · Page 8Linked to original sources
PubMed1986

The United Kingdom Cyclosporin Quality Assessment Scheme.

Data from a quality assessment scheme designed to test the measurement of cyclosporin are presented. Almost all of the participating 27 centres were using a radioimmunoassay for the measurement and, during the course of 16 months, a number of variables were tested, including accuracy, sensitivity, recovery of added cyclosporin, and within- and between-assay reproducibility. Accuracy of the measurement, judged by the mean results for spiked samples, was good, but values varied widely. Sensitivity tended to be overestimated, with a significant number of false-positive results being reported. The precision profile for the assay showed that there was no intrinsic difference in the precision of measurement using either plasma or whole blood as the sample matrix; but reproducibility for patient samples tended to be better using blood because drug concentrations are higher compared with plasma. We conclude that, whereas the results overall were encouraging, there were wide between-centre variations for the measurement, which could be compounded even further by the use of plasma or serum as the sample matrix.

Cyclosporins↗
PubMed1986

Peripheral neutrophil inclusions in amiodarone treated patients.

In 14 patients receiving chronic amiodarone therapy the appearance of multilamellar inclusion bodies in peripheral blood neutrophils was related to both plasma concentrations of amiodarone and its desethyl metabolite and unwanted effects of the drug. Seven of the patients had well defined inclusion bodies. In this group mean amiodarone and desethylamiodarone concentrations were significantly higher than in the remaining seven patients and all but one had unwanted effects of the drug. Of the seven patients without inclusion bodies only one, with high plasma amiodarone and desethylamiodarone concentrations, had unwanted effects of the drug. It is concluded that the appearance of multilamellar bodies in the blood neutrophils of amiodarone-treated patients may help to distinguish those patients at risk of long-term amiodarone toxicity.

Adult↗
PubMed1986

The effect of vehicle on the oral absorption of cyclosporin.

Twelve healthy volunteers received four separate doses of cyclosporin (5 mg kg-1). On three occasions the neat oil suspension (Sandimmun) was given dispersed in a different liquid vehicle and on one occasion the suspension was taken directly. Measurement of whole blood cyclosporin concentrations by radioimmunoassay showed no significant difference in the pharmacokinetic parameters of absorption between the neat preparation and the three dispersants used (milk, milk + chocolate flavouring and orange juice).

Adult↗
PubMed1986

Intravenous and oral amiodarone for arrhythmias in children.

Oral amiodarone was administered to 30 children (aged one week to 14 years) for treatment of resistant or life threatening tachycardias. Five children received initial intravenous medication. The mean duration of oral treatment ranged from two weeks to 64 months (mean 23 months). Infants required a higher oral dose than older children when this was calculated on the basis of body weight but not when it was calculated on the basis of body surface area, indicating that the prescribed dose of amiodarone for infants should be calculated on the basis of body surface area. Although plasma concentrations of amiodarone were similar in infants and children, the plasma concentration of the metabolite desethylamiodarone was lower in infants. The arrhythmias were effectively controlled, by amiodarone alone in 19 and by amiodarone in combination with other drugs in nine children; amiodarone was ineffective in the remaining two children. Unwanted effects were common but were not significantly related to the dose, duration of treatment, or plasma concentration of amiodarone when group results were analysed. Grey facial skin pigmentation developed in two patients who received high cumulative doses of amiodarone and in whom plasma concentrations of amiodarone were high. Four children with biochemical hepatic dysfunction had high plasma concentrations of amiodarone and a further four children who experienced sleep disturbance had required high doses of amiodarone.

Administration, Oral↗
PubMed1985

Is fibreoptic bronchoscopy in patients with lung cancer and hepatic metastases potentially dangerous?

Plasma lignocaine levels were measured in 18 patients with lung cancer undergoing fibreoptic bronchoscopy to determine whether those with hepatic metastases and disturbed hepatic function were at special risk from lignocaine toxicity. Peak plasma lignocaine levels were in fact lower in six patients with hepatic metastases and deranged hepatic function tests than in the nine patients with no evidence of hepatic metastases or dysfunction (mean +/- SEM 1.89 +/- 0.2 mg/litre and 2.60 +/- 0.3 mg/litre respectively, P not significant). The peak plasma lignocaine level did not correlate with tests of liver function but did correlate with age. Using a total dose of lignocaine of less than 400 mg, plasma lignocaine levels remained below the toxic range in all patients. The peak plasma lignocaine level correlated significantly with the amount of drug administered directly into the bronchial tree (P less than 0.05) rather than total dose administered. Patients with hepatic metastases from lung cancer do not appear to be at an increased risk from the toxic effects of lignocaine topical anaesthesia if moderate doses are used.

Administration, Topical↗
PubMed1985

Use of amiodarone and digoxin specific Fab antibodies in digoxin overdosage.

A 61 year old man with mild aortic stenosis and chronic depression took 12.5 mg digoxin in a suicide attempt. Ventricular tachycardia and fibrillation were resistant to lignocaine and to phenytoin but responded to intravenous amiodarone, with restoration of pacing. Because of persistent hyperkalaemia he was also treated with Fab fragments of digoxin specific antibody, which bound most of the ingested digoxin. It is suggested that the treatment of choice in severe digoxin poisoning is amiodarone for ventricular arrhythmias followed by pacing if necessary and the use of Fab antibody fragments if hyperkalaemia persists.

Amiodarone↗
PubMed1985

Use of amiodarone during pregnancy.

Two cases are reported in which amiodarone was administered during pregnancy for longer periods than has been reported previously. Limited placental transfer of amiodarone and its desethyl metabolite was observed in both cases. A normal child resulted from each pregnancy despite, in one case, amiodarone therapy throughout the entire pregnancy. However, caution is urged in the use of amiodarone during pregnancy in view of the limited data available.

Adult↗
PubMed1985

Amiodarone and its desethyl metabolite: tissue distribution and morphologic changes during long-term therapy.

The pharmacokinetic characteristics of amiodarone suggest extensive tissue deposition. We confirmed this by measuring tissue concentrations of the drug and of its major metabolite, desethylamiodarone, in human tissues. These were obtained at autopsy (n = 9), surgery (n = 7), or biopsy (n = 2) from 18 patients who had been treated with amiodarone for varying periods of time. High concentrations of amiodarone were found in fat (316 mg/kg wet weight in autopsy specimens, 344 mg/kg wet weight in biopsy specimens). Amiodarone and desethylamiodarone concentrations (mg/kg wet weight, autopsy samples) were also high in liver (391 and 2354), lung (198 and 952), adrenal gland (137 and 437), testis (89 and 470), and lymph node (83 and 316). We also found high concentrations of amiodarone (306 mg/kg wet weight) and desethylamiodarone (943 mg/kg wet weight) in abnormally pigmented ("blue") skin from patients with amiodarone-induced skin pigmentation. These values were 10-fold higher than those in unpigmented skin from the same patients. These high concentrations were associated with lysosomal inclusion bodies in dermal macrophages in the pigmented skin. The inclusion bodies were intrinsically electron dense and were shown to contain iodine by energy dispersive x-ray microanalysis. Lysosomal inclusion bodies shown by electron microscopy to be multilamellar were seen in other tissues. These tissues included terminal nerve fibers in pigmented skin, pulmonary macrophages, blood neutrophils, and hepatocytes and Kupffer cells. These characteristic ultrastructural findings occur in both genetic lipidoses and lipidoses induced by other drugs, e.g., perhexiline. We conclude that during therapy with amiodarone, widespread deposition of amiodarone and desethylamiodarone occurs. This leads to ultrastructural changes typical of a lipidosis. These changes are seen clearly in tissues associated with the unwanted effects of amiodarone, e.g., skin, liver and lung.

Adolescent↗