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Biomedical subjects

D W Holt

Publications and source records attributed to D W Holt.

At least 127 records · Page 7Linked to original sources
PubMed1988

Experience with flecainide for the treatment of cardiac arrhythmias in children.

We treated 22 children, aged 3 days to 16 years 6 months (median 11 years 1 month), with flecainide for a variety of arrhythmias where a Class I agent was indicated. In 16, conventional antiarrhythmic treatment had failed. Structural heart disease was present in nine. The arrhythmia was paroxysmal re-entry atrioventricular tachycardia in nine; paroxysmal atrial tachycardia, flutter or fibrillation in five; paroxysmal ventricular tachycardia in five and frequent ventricular extrasystoles (with couplets) in three. Sinus rhythm was achieved in all four children who received flecainide during tachycardia (three received intravenous flecainide, one oral). During follow-up of 3-24 months (median 12 months), arrhythmia control was obtained in 13 children (59%). Combination therapy was used in seven of these; with digoxin in four and a beta blocker in three. Flecainide doses used in this study ranged from 1-11 mg kg-1 day-1 (median 4 mg kg-1 day-1), 25-297 mg m-2 day-1 (median 113 mg m-2 day-1). The median, pre-dose flecainide concentration in those responding to therapy was 225 micrograms l-1 and in those failing to respond was 417 micrograms l-1. An arrhythmogenic effect occurred in one child.

Adolescent↗
PubMed1988

The influence of haematocrit on blood cyclosporin measurements in vivo.

The influence of haematocrit on blood cyclosporin measurements has been studied in 276 paired blood and plasma samples from 21 renal transplant patients. A highly significant correlation was found between blood and plasma cyclosporin concentrations, r = 0.8744, but the correlation between blood or plasma cyclosporin and haematocrit was not significant. The ratio of blood/plasma cyclosporin did not significantly increase with increasing haematocrit. It was concluded that in vivo the influence of haematocrit on the measurement of blood cyclosporin concentrations was negligible.

Cyclosporins↗
PubMed1988

Monoclonal antibodies for radioimmunoassay of cyclosporine: a multicenter comparison of their performance with the Sandoz polyclonal radioimmunoassay kit.

The performance of a radioimmunoassay kit containing monoclonal specific and nonspecific antibodies to cyclosporine (Sandimmun-Kit; Sandoz Ltd., Basle, Switzerland) was compared with that of the original Sandoz polyclonal radioimmunoassay kit (Ciclosporin RIA-Kit). A total of 1320 blood and plasma samples from patients receiving cyclosporine after kidney, heart, liver, and bone-marrow transplantation were analyzed at six centers. For blood samples the median result on using the specific assay was about 50% of the polyclonal assay result after kidney and bone-marrow transplantation, about 33% after heart and liver transplantation; comparable figures for plasma samples were 70 and 40%. The monoclonal nonspecific-antibody assay produced results 10% to 140% higher than polyclonal-assay results, depending on sample matrix and transplant indication; the largest difference was seen in samples from heart- and liver-transplant recipients. Evidently the specific-antibody assay provides a convenient alternative to high-performance liquid chromatography for specific measurement of the drug, but the role of the new nonspecific antibody, possessing an even broader spectrum of cross-reactivity with cyclosporine metabolites than the original polyclonal antiserum, has yet to be defined.

Antibodies↗
PubMed1987

HPLC measurement of penticainide and desalkylpenticainide in biological fluids.

A simple HPLC method has been developed to measure the antiarrhythmic agent penticainide and its N-desalkyl metabolite in biological fluids. Solvent extraction of a small (200 microL) sample volume with direct analysis of the extract is used to measure the plasma and urinary concentrations of these compounds attained during chronic therapy, although a larger sample volume (1.0 mL) and prior concentration of the extract are required for single oral dose work. In each case chromatographic analysis is performed using a microparticulate (5 microns) silica column and methanolic ammonium perchlorate (10 mM, pH 6.7) as eluent with UV detection (260 nm). No endogenous sources of interference have been encountered and potential interference from other drugs is minimal.

Anti-Arrhythmia Agents↗
PubMed1987

Flecainide--an intravenous infusion regimen.

An intravenous infusion regimen for flecainide was studied in 12 patients. Therapeutic drug levels were rapidly established and maintained throughout the 48-h infusion period. Two patients were withdrawn because of possible drug related problems, but in general the regimen seemed both effective and well tolerated.

Aged↗
PubMed1987

Plasma flecainide concentrations following acute myocardial infarction.

Plasma flecainide concentrations were measured in 10 patients with acute myocardial infarction. Following an oral loading dose of 300 mg plasma concentrations were highly variable and unpredictable. Subsequently, doses of 150 mg twice daily produced mean plasma flecainide concentrations consistently above 400 micrograms/1 within 48 hours. Oral flecainide is, therefore, subject to the same problems of varying oral bioavailability as other antiarrhythmic drugs tested following acute myocardial infarction and, initially, an intravenous regime remains preferable. Mild pulmonary oedema occurred in six patients and, although it responded to one dose of frusemide and did not recur, flecainide must be used with caution when significant left ventricular dysfunction is suspected.

Administration, Oral↗
PubMed1987

Cardiac glycoside toxicity resulting from cough linctus abuse.

Proprietry cough medicines are often abused by drug addicts as they are freely available and, in many instances, contain narcotic substances. A variety of other compounds are present in these products, including compounds structurally related to the commonly prescribed cardiac glycosides. We report a case in which severe cardiac glycoside toxicity resulted from the abuse of such a preparation.

Adult↗
PubMed1986

Blood cyclosporin concentrations and renal allograft dysfunction.

Forty nine renal allograft recipients taking oral cyclosporin suffered 76 episodes of renal dysfunction within six months of transplantation. These episodes were diagnosed as graft rejection or cyclosporin induced nephrotoxicity on the basis of histological findings in allograft biopsy specimens and the response to treatment. Mean predose blood cyclosporin concentrations measured by radioimmunoassay during the week before the onset of renal dysfunction were significantly higher when the cause was cyclosporin toxicity rather than graft rejection (392 v 741 nmol/l (471 v 891 ng/ml). During this period there was a significant association between both the frequency of measurements above 666 nmol/l (800 ng/ml) and the diagnosis of toxicity and the frequency of measurements below 333 nmol/l (400 ng/ml) and the diagnosis of allograft rejection. Cyclosporin measurements made at the time of biopsy and reference to the highest or lowest concentrations measured during the week preceding biopsy were of less value in distinguishing between the two groups. Despite lacking specificity for the parent compound, the radioimmunoassay used produced results which were of clinical value in optimising cyclosporin treatment.

Adult↗
PubMed1986

Measurement of penbutolol and 4-hydroxypenbutolol in plasma or serum by HPLC.

A simple HPLC method for penbutolol and 4-hydroxypenbutolol assay has been developed. Plasma or serum (200 microliters) is vortex-mixed (30 s) with Tris solution (2 M, pH 10.6) containing an internal standard (50 microliters) and methyl t-butyl ether (200 microliters). After centrifugation, the extract (100 microliters) is analysed using an unmodified silica column (250 x 5 mm ID) and iso-octane-methanol-methyl t-butyl ether (55:25:20) containing ammonium perchlorate (10 mM, pH 5.7) as eluent and with fluorescence detection. No interference has been encountered and the limit of accurate measurement for both compounds is 5 micrograms/l.

Chromatography, High Pressure Liquid↗
PubMed1986

Verapamil and breast-feeding.

Concentrations of verapamil and norverapamil were measured in the plasma and breast milk of a woman receiving 120 mg verapamil three times daily. Whilst the concentrations of verapamil in breast milk averaged about 64% of those in maternal plasma no drug could be detected in the plasma of the infant. It is concluded that maternal therapy with verapamil does not pose a hazard to the suckling infant.

Adult↗
PubMed1986

Measurement of plasma disopyramide as a guide to paediatric use.

We have studied the relationship between age, daily dose, plasma concentration and clinical efficacy of disopyramide in a group of paediatric patients. Twelve children with ventricular and 3 with supraventricular arrhythmias were treated with oral disopyramide. The initial dose was 3-6 mg/kg per day. This was adjusted until a pre-dose plasma concentration greater than 2 mg/I was achieved. Seven patients were judged to have responded to the treatment on clinical criteria. No symptoms or signs of toxicity were observed. In some of the children the dose of disopyramide required to achieve a plasma concentration greater than 2 mg/l was greatly in excess of the normal adult dose. Generally the youngest children required the highest dose, but the variation was wide. The dose could not be predicted from the age, the body weight or the surface area of the patient. In children high doses of disopyramide may be needed to achieve effective plasma concentrations of the drug; such doses are not associated with adverse effects. Measurement of the plasma concentration is necessary to guard against premature termination of therapy.

Administration, Oral↗