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R O Fullinfaw

Publications and source records attributed to R O Fullinfaw.

10 recordsLinked to original sources

A randomised controlled clinical trial of the efficacy of family-based direct observation of anti-tuberculosis treatment in an urban, developed-country setting.

SETTING: A randomised, controlled clinical trial of the effectiveness of a family-based programme of directly observed treatment (DOT) for tuberculosis. METHODS: TB patients seen in Victoria, Australia, were randomly allocated to DOT observed by a family member (FDOT), or to standard supervised but non-observed therapy (ST). The outcome measure was compliance, measured by blinded testing of isoniazid levels in urine. An intention-to-treat analysis was used. RESULTS: Of 173 patients, 87 were allocated to FDOT and 86 to ST. Only 58% in the FDOT group were able to receive FDOT, the major reason being living alone and not having a family member to observe treatment. The rate of non-compliance was 24% (41/173), with no significant difference between FDOT (22/87) and ST (19/86). No clinical or socio-demographic variable predicted compliance. CONCLUSIONS: We were unable to demonstrate a benefit of FDOT in an urban, industrialised country setting. FDOT may be more appropriate in developing countries, where extended family support is often available and the burden of TB is much higher. Poor compliance and the difficulty in predicting non-compliance shown in this study highlights the need for DOT for all TB patients.

Adolescent↗

Ponalrestat does not cause a protein binding interaction with warfarin in diabetic patients.

Ponalrestat (Statil, ICI; Prodiax, Merck Sharp and Dohme) is an aldose reductase inhibitor which is highly protein bound. Ponalrestat markedly displaced warfarin from its protein binding in vitro at a concentration of 500 micrograms ml-1, but not at a concentration of 50 or 100 micrograms ml-1. Twelve diabetic patients (six males), age range 38-65 years, in receipt of chronic stable warfarin therapy, were given ponalrestat (600 mg daily) for 2 weeks in an open trial. A matching placebo tablet was administered for 1 week before and after the active treatment period. Patients were seen ten times (four times during the ponalrestat phase), and during the ponalrestat phase, plasma samples were also taken before and at 3 h after the daily dose of ponalrestat. At none of the visits was there any significant change in prothrombin ratio (INR), plasma total or unbound warfarin concentrations, or percentage protein binding of warfarin. No clinical complications of combination treatment were detected. The maximum ponalrestat concentration observed in the patients was approximately 100 micrograms ml-1. We conclude that no significant interaction between these drugs occurs at the doses of ponalrestat studied.

Adult↗

Unbound phenytoin plasma concentrations in patients comedicated with sodium valproate--the predictive value of plasma albumin concentration.

1. Phenytoin protein binding in epileptic patients on phenytoin as monotherapy has been compared with protein binding in patients treated with both phenytoin and sodium valproate. In addition the relative value of assayed total phenytoin plasma concentrations and assayed unbound phenytoin plasma concentrations and the value of predicted unbound phenytoin plasma concentrations in predicting phenytoin toxicity has been assessed. 2. The mean phenytoin unbound fraction for patients taking sodium valproate (0.122) was significantly greater than for those on monotherapy (0.082). 3. There were six episodes of clinical toxicity. In five toxic episodes the assayed unbound phenytoin plasma concentration was a better reflection of toxicity than the assayed total phenytoin plasma concentration, and four of these occurred in patients on sodium valproate. 4. Unbound phenytoin plasma concentrations were predicted from a single regression equation correlating all assayed total phenytoin plasma concentrations with assayed unbound phenytoin plasma concentrations, from two separate regression equations for each group of patients, and from the correlation between phenytoin protein binding and plasma albumin concentration. 5. The unbound phenytoin plasma concentrations predicted from the two regression equations were statistically no less effective than the assayed unbound phenytoin plasma concentrations in assessing toxicity. 6. Despite a correlation between plasma albumin concentrations and phenytoin protein binding, the use of albumin concentrations in predicting unbound phenytoin plasma concentrations appeared to be of little additional benefit.

Adult↗

Screening procedure for stimulant laxatives in urine using high-performance liquid chromatography with diode array detection.

We describe a liquid chromatographic screening procedure for the detection of stimulant laxatives in urine. A 2-ml urine sample was incubated with 500 U of beta-glucuronidase for 2 h at 60 degrees C. The sample was acidified with sodium acetate (pH 5.0) and extracted with 5 ml of an isopropanol-chloroform (1:9) mixture. The organic layer was cleaned up further by washing with 5 ml disodium hydrogen-phosphate (pH 7.5) before being transferred to a conical tube and evaporated to dryness. The residue was reconstituted in 100 microliters mobile phase and 3 microliters were injected onto a Hewlett-Packard Hypersil ODS (5 microns) column. The ultraviolet absorbance of the eluent was monitored at 225 nm. Rhein, bisacodyl diphenol, bisoxatin diphenol, phenolphthalein, bisacodyl, bisoxatin and danthron all eluted within 6 min. The screen was evaluated using urine specimens obtained from 19 patients who claimed they had taken one or more of the laxatives under consideration within the past 48 h. Only two patients who claimed to have taken Coloxyl and Danthron showed negative results. Eighteen of twenty laxatives (90%) taken by the patients were detected and their identity verified by plotting post-run ultraviolet spectra. We therefore conclude that the screen is sufficiently reliable to be of help in the early detection of surreptitious abusers of stimulant laxatives.

Adult↗

Liquid chromatographic screening of diuretics in urine.

We describe a liquid chromatographic screening procedure for the detection, in urine, of twelve of the fifteen potassium-depleting diuretics available in Australia. A 2-ml urine sample was acidified with NaH2PO4 (pH 4.1) and extracted with 4 ml ethyl acetate. The sample was cleaned up further by washing with 5 ml Na2HPO4 (pH 7.5). The ethyl acetate was then evaporated to dryness, the residue reconstituted in 100 microliters mobile phase and 5 microliter were injected onto a Merck LiChrosorb RP-18 (5 microns) column. The ultraviolet absorbance of the eluent was monitored at 271 nm for 10 min. The screen was evaluated by giving each of thirty volunteers the lowest recommended dose of one of the diuretics in the study and obtaining urine samples 4, 8 and 24 h after having taken the dose. Twelve diuretics, chlorothiazide, hydrochlorothiazide, quinethazone, chlorthalidone, methyclothiazide, clopamide, frusemide, metolazone, mefruside, bendrofluazide, cyclopenthiazide and bumetanide, were all detectable up to 24 h after a dose. We therefore conclude that the screen would be reliable for the detection of these diuretics in urine.

Chromatography, High Pressure Liquid↗

Plasma concentrations of unbound valproate and the management of epilepsy.

The range of protein binding of valproate and the use of unbound and total plasma concentrations of the drug were studied in an outpatient population of 70 epileptics. The unbound fraction of plasma valproate ranged from 4.2% to 11.7% with a median of 7.1%. A non-linear relationship was found between unbound and total plasma valproate concentrations and was best described by a cubic regression (r2 = 0.88). This concentration dependent protein binding was also demonstrated by a linear relationship between total plasma valproate concentration and unbound fraction (r = 0.46). As expected, there was no correlation across the patient population between plasma concentrations of valproate and seizure frequency. In an individual patient, however, plasma valproate levels usually correlated with change in clinical status, although this correlation was no better for unbound levels than total levels. There were only three patients in whom unbound valproate levels correlated better with clinical effect than total levels, whereas there were six patients in whom total levels correlated better than unbound levels. It is therefore concluded that monitoring sodium valproate therapy with unbound concentrations is rarely helpful and the routine use of unbound valproate levels cannot be advocated.

Adolescent↗

Changes in clearance of sodium valproate with changes in dose.

The relationship between total sodium valproate concentrations and drug clearance was studied in four patients, by the evaluation of clearance at two different doses. In each patient, the average unbound fraction for a dosing interval increased with increase in sodium valproate dose. Despite this increase in unbound fraction, there was no increase in total drug clearance, and in each patient there was a decrease in clearance of the unbound drug. These findings suggest either that the drug is restrictively cleared and there is a dose-related decline in intrinsic clearance, or, contrary to previous reports, that sodium valproate is cleared nonrestrictively.

Adult↗