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Biomedical subjects

D W Holt

Publications and source records attributed to D W Holt.

At least 199 records · Page 11Linked to original sources
PubMed1979

Cardiac consequences and treatment of disopyramide intoxication: experimental evaluation in dogs.

A slow (1.18 mumol.kg-1.mm-1) intravenous infusion of disopyramide (mol.wt 339) was given to 8 adult Beagle dogs. An initial phase of slow decline in cardiac output and broadening of the QRS complex on the ECG, with systolic blood pressure maintained above 13.5 kPa (100 mmHg), was followed by a phase of rapid circulatory failure without a correspondingly dramatic change in ECG appearances. Underventilation and cardiac arrhythmias were observed only in the agonal phase after several minutes of circulatory arrest. They were not therefore the primary cause of death, which was due to failure of myocardial contractility. Three positively inotropic drugs (isoprenaline, dopamine, and glucagon) are shown to be capable of restoring the failing circulation, provided they are given before the phase of complete circulatory standstill. In this respect isoprenaline appears superior to dopamine and glucagon.

Animals↗
PubMed1979

Gas-liquid chromatographic measurement of lignocaine in small samples of canine myocardium after enzymatic digestion.

A method is described whereby lignocaine can be measured in small samples of canine myocardium. A proteolytic enzyme is used to digest the tissue, and the drug, together with an internal standard, is subsequently extracted into an organic solvent and measured by gas-liquid chromatography. The method is reproducible using tissue samples as small as 50 mg and appears to be suitable for the measurement of a number of drugs in small samples of tissue.

Animals↗
PubMed1979

A schedule for combined intravenous and oral dosing with mexiletine.

A combined intravenous and oral dosage regime for mexiletine has been evaluated in volunteer subjects. Therapeutically effective plasma concentrations of the drug were achieved rapidly and maintained over a four-hour period. Side-effects were minimal and the scheme would be suitable for the anti-arrhythmic protection of patients being transported to hospital and for the treatment of patients receiving hospital or, even, domicilliary care.

Administration, Oral↗
PubMed1978

Fatal overdosage with disopyramide.

The most common clinical finding in five patients who died after deliberately taking overdoses of disopyramide was an early loss of consciousness after an apnoeic episode. An initial response to resuscitation and antiarrhythmic drugs in four patients was not sustained and these patients deteriorated rapidly with cardiac arrhythmias and loss of spontaneous respiration. At necropsy the appearance of the lungs in four cases was consistent with pulmonary congestion secondary to left ventricular failure.

Adolescent↗
PubMed1977

Digoxin measurements in general practice.

1 As part of a prospective study on the use of digoxin in a general practice, plasma digoxin concentrations were measured in all patients receiving the drug. 2 A low mean plasma digoxin concentration was observed, suggesting a cautious approach to digitalization. 3 The correlation between plasma digoxin concentration and signs or symptoms commonly used in the assessment of digoxin effect was poor. 4 It was concluded that the measurement of plasma digoxin could be of assistance in a variety of clinical settings within a general practice.

Aged↗
PubMed1976

Penetration of digoxin into cerebrospinal fluid.

The concentration of digoxin in the cerebrospinal fluid (CSF) of ten patients receiving conventional oral doses of this cardiac glycoside has been measured by a radioimmunoassay technique. Digoxin was undetected in eight patients and barely detectable in two, suggesting the presence of a significant blood-CSF barrier for digoxin. The implication of these findings is discussed.

Adult↗
PubMed1975

Postmortem assay of digoxin by radioimmunoassay.

Analysis of postmortem blood samples from patients previously on maintenance digoxin therapy suggests that the results are of value in assessing the degree of digitalization at the time of death. Control cases gave results within the normal therapeutic range wheras of six cases in which digoxin was suspected of being implicated in the death five had 'serum' digoxin levels above the therapeutic range. Differences in digoxin concentration were noted in blood collected from three sites in the body, and it is suggested that postmortem blood should be collected from the leg veins if assessment of antermortem digitalization is to be made.

Aged↗
PubMed1975

The treatment of digoxin overdosage.

A case of digoxin overdosage is presented in which hemodialysis and forced diuresis were employed in the treatment. Hemodialysis was found to be ineffective in removing significant amounts of the drug and additional experimental work using a dog confirmed that forced diuresis failed to alter the rate of digoxin excretion.

Animals↗
PubMedDate not supplied

A microparticle enzyme immunoassay to measure sirolimus.

Measurement of sirolimus as a guide to therapy is widely accepted. Since the commercial introduction of the drug, the only method available to measure blood concentrations has been high-performance liquid chromatography (HPLC). Only a limited number of centers have the facilities to perform this technique and, as a result, the measurement of the drug has been performed in central laboratories, often some distance from the clinical centers. This article describes a single-center assessment of a new immunoassay to measure sirolimus, including a comparison between immunoassay results and a chromatographic technique. Calibration accuracy was good, reproducibility at 11 ng/mL was better than 6%, and sensitivity was better than 2 ng/mL; all these parameters are appropriate for routine clinical use. There was a mean positive bias of almost 20% for the measurement of sirolimus in clinical samples from kidney transplant patients receiving the drug, compared with HPLC. This bias was most likely due to cross-reactivity with metabolites of the drug and was of the order noted when an earlier configuration of this immunoassay was used in clinical practice. We conclude that, despite the analytical bias, this immunoassay offers a viable alternative to the use of HPLC and would be an assay suitable for implementing at local centers.

Biotransformation↗