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D W Holt

Publications and source records attributed to D W Holt.

At least 19 recordsLinked to original sources
PubMed1992

Smoking and decreased fertilisation rates in vitro.

To examine possible mechanisms for the association between cigarette smoking and reduced fertility, we have measured the concentration of the nicotine metabolite cotinine in ovarian follicular fluid collected at the time of oocyte recovery during treatment for in-vitro fertilisation. In a group of women in whom follicular fluid cotinine could not be detected (limit of accurate measurement 20 ng/ml) 116 oocytes were collected, of which 84 became fertilised (72%), whereas among women with cotinine concentration greater than 20 ng/ml 20/45 (44%) oocytes did so (p < 0.01). The median fertilisation rates for individuals (range 1-8 eggs each) in the high and low cotinine groups were 57% and 75%, respectively (p < 0.05). These findings suggest that infertile women should be advised to stop or reduce smoking generally, and especially before treatment by in-vitro fertilisation.

Adult↗
PubMed1992

Myocardial magnesium depletion associated with prolonged hypomagnesemia: a longitudinal study in heart transplant recipients.

OBJECTIVES: This study was carried out to establish prospectively the incidence and relation of hypomagnesemia and myocardial magnesium depletion after heart transplantation. BACKGROUND: No serial in vivo study of the relation of serum with tissue magnesium has been described. Myocardial magnesium depletion is associated with intracellular calcium overload, an increased incidence of cardiac arrhythmia and changes in coronary vasculature similar to those seen in the accelerated atherosclerosis that compromises graft survival after transplantation. METHODS: In a prospective study in 19 consecutive patients, serum and myocardial magnesium content were measured serially for 9 months after heart transplantation. Blood cyclosporine was assayed simultaneously. RESULTS: The incidence of hypomagnesemia was 100% during the 9-month study period, with lowest levels at 3 months (mean 0.80 vs. 0.64 mmol/liter, p less than 0.002). Myocardial magnesium depletion developed in 94% and was persistent in 55%; the lowest levels occurred at 6 months (mean 33.6 vs. 30.1, mumol/g, p less than 0.04). Hypomagnesemia predated decreases in myocardial magnesium by 2 to 6 weeks. Peak cyclosporine levels correlated positively with the decrease in serum magnesium. Clinical events were rare. CONCLUSIONS: This is the first report of serial measurement of tissue magnesium. Persistent hypomagnesemia is invariably accompanied by myocardial magnesium depletion in the transplanted heart. Reciprocal calcium overload and adverse changes in coronary vasculature would be expected from previous studies and merit further investigation. Should the implications of this study extend to the native heart, myocardial magnesium depletion may contribute to the high incidence of fatal arrhythmic events observed in patients with heart failure, who commonly have persistent hypomagnesemia.

Cyclosporine↗
PubMed1992

Cyclosporin monitoring: its role in autoimmune indications.

This paper describes some of the methodological problems related to the measurement of cyclosporin. The clinical value of the measurements following organ transplantation are discussed and those areas also applying to autoimmune indications are highlighted. It is concluded that the routine use of cyclosporin monitoring in samples from patients receiving the drug for autoimmune indications is unlikely to be of significant value as a guide to efficacy or toxicity. However, some settings, such as suspected poor patient compliance, for the avoidance of potential drug interactions and for research on the absorption of new formulations are considered to be useful applications of the methodology.

Autoimmune Diseases↗
PubMed1992

Radioimmunoassays for spirapril and its active metabolite spiraprilate: performance and application.

Radioimmunoassays for a nonsulfhydryl angiotensin converting enzyme inhibitor prodrug--spirapril--and its active metabolite--spiraprilate--are described. Nonextraction equilibrium assays using antibodies with a high specificity for spirapril or spiraprilate were used, with charcoal separation of bound and free tracer. Within-assay reproducibility (CV%) was less than 20% in the concentration range 0.5-40 micrograms/L for both analytes and the comparable value for between-assay reproducibility was less than 25%. Results for external quality control samples were in good agreement with the expected values of 0-250 micrograms/L (spirapril, r = 0.997) and 0-300 micrograms/L (spiraprilate, r = 0.999). Overall, samples circulated to four laboratories gave good agreement for measured values, including one center using gas chromatography-mass spectrometry analysis for the two compounds. Data are presented to show the suitability of these two assays to the measurement of spirapril and spiraprilate in clinical samples from assays to the measurement of spirapril and spiraprilate in clinical samples from dose-ranging and bioequivalence studies. Results are also shown relating drug plasma concentration data to a measurement of the pharmacodynamic effects of spiraprilate, namely inhibition of angiotensin converting enzyme activity. It is concluded that these assays have the sensitivity for use in studies to model the relationship between the pharmacokinetics and pharmacodynamics of the two compounds.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

The effect of age on the pharmacokinetics of pentisomide.

The effects of age on the pharmacokinetics of pentisomide (CM7857), an orally effective antiarrhythmic agent, were studied in two groups of volunteers. Sixteen young volunteers (mean age 26.4 years) and 10 elderly volunteers (mean age 67.8 years) received a single 200 mg oral dose of pentisomide. Mean AUC was larger and terminal elimination half-life longer in the elderly subjects, due to a decrease in total plasma clearance of pentisomide in the elderly. This decrease was due to a reduction in renal clearance of the drug which was paralleled by a significantly lower creatinine clearance in the elderly subjects. Dosage reduction, or a reduced frequency of dosing of pentisomide would be necessary in the elderly or those with impaired renal function.

Administration, Oral↗
PubMed1991

Monitoring cyclosporin: is it still important?

This paper reviews the current data which provide a rationale for the measurement of cyclosporin as a guide to therapy. Methodological problems related to sample matrix and analytical technique are considered, and the most commonly used methods considered. Factors which could influence the clinical interpretation of cyclosporin measurements are examined, including other drug therapy, compliance with therapy, cyclosporin metabolites, pharmacokinetic variables and sample timing. It is concluded that, whilst isolated measurements do not offer a definitive diagnostic tool, taken in context they can be of considerable value in optimising therapy.

Cyclosporine↗
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↗