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Biomedical subjects

D W Holt

Publications and source records attributed to D W Holt.

At least 109 records · Page 6Linked to original sources
PubMed1991

Micro method of analysis for magnesium in myocardial biopsies.

We developed a single-stage technique involving a proteolytic enzyme (pepsin) for the solubilization of cardiac muscle to measure magnesium in tissue. This new method has been developed specifically for use with very small cardiac biopsy samples (less than 1 mg) obtained with modern myocardial biopsy forceps. Pepsin digestion of the tissue releases magnesium ions into solution and, after centrifugation and dilution with lanthanum chloride, the resulting supernate is suitable for analysis by atomic absorption spectrometry. Recovery of magnesium after a single digestion approaches 99%. In direct comparison studies of pepsin digestion and a traditional method involving nitric acid extraction, the pepsin digestion consistently yielded more magnesium. In contrast to traditional methods of tissue solubilization, pepsin digestion is well suited to extraction of magnesium from the small biopsy samples commonly presented for analysis in clinical practice.

Biopsy↗
PubMed1991

Quality assurance for cyclosporin assays in body fluids.

The United Kingdom Cyclosporin Quality Assessment Scheme has now over 6.5 years experience of the measurement of cyclosporin. The scheme has more than 154 member laboratories in 30 countries. Each laboratory is sent three samples a month for analysis and the returned results allow the laboratories to measure their performance relative to their peers. The data generated by the centres makes it possible to assess independently the performance of the methods available for the measurement of cyclosporin. The data for the 12 month period June 1989 to May 1990 were analysed. Over that period, the proportion of laboratories using plasma rather than whole blood fell from 9% to 7%. Eight different methods were available for the measurement of the drug but three techniques accounted for over three quarters of the results returned; the specific radioimmunoassays Cyclo Trac-SP (48%), and Sandimmun-SP (21%), and high performance liquid chromatography (8%). The specific immunoassays showed a positive bias, approximately 10%, relative to HPLC when measuring the drug in patient samples. However, there are no data to suggest these differences are of clinical significance and the specific immunoassays can be recommended in preference to HPLC because of their better precision and ease of use. The poor performance of some laboratories and the increasing number of methods available for the measurement of cyclosporin suggest that there is a continuing need for the external quality assessment of this measurement.

Chromatography, High Pressure Liquid↗
PubMed1990

High performance liquid chromatographic measurement of bisoprolol in plasma.

A simple high performance liquid chromatographic method has been devised for the measurement of bisoprolol in plasma or serum. The sample (200 microL) is vortex mixed for 30 s with 2 M Tris solution (50 microL), aqueous internal standard (benzimidazole, 2.0 mg/L, 50 microL) and methyl t-butyl ether (200 microL). After centrifugation (9950 x g, 2 min), a portion of the resulting extract is analysed on a microparticulate (5 microns) silica column using 1 mM camphorsulphonic acid in methanol as the mobile phase. Detection is by fluorescence at an excitation wavelength of 215 nM. The lower limit of accurate measurement for the assay is 10 micrograms/L (CV% = 8.9, n = 9) with a lower limit of detection of 5 micrograms/L. There is minimal interference from either commonly prescribed drugs or endogenous compounds.

Bisoprolol↗
PubMed1989

High performance liquid chromatographic measurement of lignocaine in tissue samples following transabdominal placental biopsy.

A method is described for the measurement of lignocaine in small samples of fetal and placental tissue. Tissue samples (ca 100 mg) are digested using a preteolytic enzyme. Lignocaine and an internal standard are extracted into methyl tert-butyl ether and analysed by high-performance liquid chromatography with electrochemical detection (+1.0 V vs Ag/AgCl). The limit of accurate measurement is better than 0.1 mg/kg wet weight for a 100 mg sample. This method has been used to assess fetal exposure to the drug when used as a local anaesthetic during transabdominal placental biopsy (chorionic villus sampling). The range of lignocaine concentrations found in the tissue samples was large (from less than 0.04 mg/kg wet weight to 15.4 mg/kg wet weight) although most samples contained less than 1.0 mg lignocaine/kg wet weight.

Animals↗
PubMed1989

The digoxin-amiodarone interaction.

To assess the cause of the digoxin-amiodarone interaction, the systemic availability and renal excretion of digoxin were examined in 10 patients. Patients were studied before and after 1 week and 6 weeks of concurrent amiodarone therapy, and four were also studied after 4-8 months. Mean (+/- SD) peak plasma digoxin concentration rose from 1.55 +/- 0.6 microgram /1 prior to amiodarone therapy to 2.85 +/- 1.3 micrograms/1 after 1 week of combined therapy (p less than 0.01). Mean AUC also rose from 7.2 +/- 2.1 micrograms/1.h to 12.1 +/- 6.4 micrograms/1.h (p less than 0.01) during this period. Mean peak plasma digoxin concentration and AUC remained elevated after 6 weeks and, in the patients studied, at 4-8 months. Mean urinary digoxin clearance remained unchanged. Plasma amiodarone and desethylamiodarone concentrations were consistent with the prescribed doses. This study confirmed previous findings of raised plasma digoxin concentrations following the addition of amiodarone. It has also shown that this interaction is sustained for at least several months. The cause has not been fully elucidated but does not appear to be due to a change in the renal clearance of digoxin.

Aged↗
PubMed1989

Paediatric use of flecainide in supraventricular tachycardia: clinical efficacy and pharmacokinetics.

Twenty three children with recurrent supraventricular tachycardia were treated with flecainide. Twenty one of these received intravenous treatment during an attack (2 mg/kg over 10 minutes). The tachycardia was terminated in 17. After an intravenous bolus of flecainide, blood samples were drawn at regular intervals for analysis of flecainide concentration over 48 hours. Pharmacokinetic variables were calculated--median terminal half life 7.5 hours, median volume of distribution 6.2 l/kg, and median plasma clearance 7.2 ml/min/kg. There was a significant correlation between half life and age. Twenty of the children received long term treatment with an oral preparation of flecainide to prevent further attacks. Twelve had no further attacks and 16 were considered to have good control. Two children suffered potentially serious arrhythmogenic effects soon after the start of oral treatment and flecainide had to be stopped. During oral treatment regular blood samples were drawn and plasma concentrations were analysed to assess the therapeutic range. This did not differ substantially from that proposed in adults (400-800 micrograms/l). Eight children were electively withdrawn from oral flecainide to see whether they really needed it. Blood samples for measurement of flecainide concentration were drawn after their last oral dose. Pharmacokinetic variables were calculated: time to maximum concentration 2 hours, median terminal half life 7.9 hours. For the combined data from patients receiving intravenous and oral treatment there was a significant correlation between elimination half life and age. An intravenous dose of 2 mg/kg over at least 10 minutes and an initial oral dose of 6 mg/kg/day in three divided doses is recommended. Treatment should be started in hospital so that children in whom the drug may be arrhythmogenic can be identified and plasma concentrations measured to identify patients in whom lack of efficacy is caused by underdosage.

Administration, Oral↗
PubMed1989

The relevance of pharmacokinetics to monitoring new antiarrhythmics.

The application of selective and sensitive methodology to the investigation of the pharmacokinetics of new antiarrthythmic drugs is described. The value of these data in the context of routine measurements as a guide to therapy is discussed. In particular, specific case histories that demonstrate the considerable within- and between-subject variation in pharmacokinetic parameters are cited and used to illustrate the potential benefits of drug monitoring. We conclude that studies designed to elucidate the pharmacokinetics of these drugs in a variety of clinical settings can be a valuable guide to assessing the patient groups for whom routine monitoring would be of particular benefit when the drugs are in general clinical use.

Anti-Arrhythmia Agents↗
PubMed1989

The continuing need for quality assessment of cyclosporine measurement.

The returns from the United Kingdom Cyclosporin Quality Assessment Scheme were analyzed for the period June 1987 to August 1988. During this time the number of laboratories in the Scheme increased from 102 to 124 and the proportion of laboratories using nonspecific assay methods declined, as did the proportion of them measuring cyclosporine in plasma. Seven different methods were used to measure the drug in blood, and the seven methods gave seven different results when used to measure patients' samples. The results, from lowest to highest, differed by a factor of approximately 3.4. The within-assay coefficient of variation (CV) was acceptable for all methods, but the between-assay and between-center CVs were poor. HPLC gave higher CVs than did the immunoassays.

Cyclosporins↗