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Biomedical subjects

A Dunne

Publications and source records attributed to A Dunne.

14 recordsLinked to original sources

Double-blind randomized clinical trial of self-administered podofilox solution versus vehicle in the treatment of genital warts.

PURPOSE: Genital warts are a highly prevalent and chronic sexually transmitted disease for which there is no completely satisfactory therapy. Conventional ablative therapy requires repeated treatment, often for months or years. This study was undertaken to evaluate the safety and efficacy of 0.5% podofilox in patient-administered treatment of penile warts. PATIENTS AND METHODS: Thirty-eight men with penile warts were randomly assigned to double-blind, self-administration of 0.5% podofilox solution or placebo, twice daily for 3 days per week for 4 weeks. Eleven podofilox and 15 placebo recipients with residual warts then received an additional 4 weeks of open-label treatment. RESULTS: By the end of treatment, podofilox recipients had their mean wart number and area reduced to 15.9% and 5.1% of baseline values, compared to 97.4% and 92.9% in the placebo group (p = 0.0001). Local adverse reactions were more common in the podofilox group, but were transient. Complete disappearance of warts was observed in 25 (53.3%) of 45 treatment courses, including open-label treatment. Recurrences of warts after therapy were frequent. Only 21% of patients remained free of warts 2 weeks after completing treatment, and subsequent recurrences were noted in all patients available for long-term follow-up, which is a common limitation of ablative therapy for genital warts. CONCLUSION: Podofilox 0.5% solution is effective in treating penile warts and is well tolerated in a self-administered regimen. Podofilox 0.5% offers potential advantages in safety and cost over podophyllin resin therapy of genital warts.

Adult

Altered sensitivity to amiloride in cystic fibrosis. Observations using cultured sweat glands.

1. Using cultured epithelia from sweat glands, derived from both cystic fibrosis and normal subjects, the relationship between amiloride concentration and the inhibition of electrogenic sodium transport was measured, under short circuit conditions. 2. The Kd for amiloride in cultures from normal subjects was 0.64 microM (n = 6) while in cultures derived from CF patients the value was 1.07 microM (n = 4). The values were significantly different (P less than 0.02, ANOVA). 3. In cultures from normal sweat glands, bathed in solutions free of permeable anions (chloride/bicarbonate), the Kd for amiloride rose to a value greater than found in CF tissues (2.3 microM). In CF epithelia subject to the same conditions the abnormally high value increased further, so that in solutions without permeable anions normal and CF cultures behaved similarly. 4. In cultures derived from normal and CF tissues lowering the sodium concentration to 10 mM also lowered the Kd for amiloride, however the shift was greater for CF cultures. 5. Several possible explanations for the results are discussed. The most probable is that the relatively more positive apical membrane potential in CF epithelia opposes the interaction of amiloride with the sodium channel, implying that complex formation is potential sensitive.

Adolescent

Estimation of noncompartmental parameters: a technical note.

Noncompartmental pharmacokinetic parameters are usually expressed in terms of the area under the so-called first moment curve and the area under the plasma concentration-time curve. These areas are normally computed by numerical integration. There is an inconsistency in the way in which they are presently estimated. This inconsistency is detailed and a consistent approach to the computation of noncompartmental parameters is outlined. The difference between the two methods is illustrated using some data from the literature.

Models, Biological

Detection of herpes simplex virus DNA from genital lesions by in situ hybridization.

Lesion specimens from 118 episodes of recurrent genital herpes were used to compare herpes simplex virus (HSV) isolation with a direct specimen test for in situ DNA hybridization utilizing a biotinylated probe. The frequency of detection of HSV was similar with both tests; HSV was isolated from 81% of vesicular lesions, 76% of pustules, and 67% of ulcers, while HSV DNA was detected in 77, 76, and 55% of lesions in these stages, respectively. Utilizing both methods, HSV was identified in 91, 94, and 79%, respectively. The sensitivity and specificity of the DNA probe in comparison to standard viral isolation in tissue culture were 92 and 63%, respectively. Seven DNA-positive, viral isolation-negative specimens were obtained from patients who had positive culture confirmation at some time subsequent or prior to enrollment, suggesting that these were true positive results. The sensitivity of the DNA probe was dependent on cellular content of the specimen, and 36 (28%) of the 127 submitted specimens had fewer than 20 nonsuperficial cells. The DNA probe was rapid and convenient; its major disadvantage was the lack of type-specific information. The performance of the probe in lower-prevalence populations and in asymptomatic shedding of HSV remains to be evaluated.

Cells, Cultured

An iterative curve stripping technique for pharmacokinetic parameter estimation.

Non-linear least-squares regression is commonly used for pharmacokinetic parameter estimation. Initial parameter estimates are required as a prelude to non-linear least-squares and the quality of the final parameter estimates may depend on these initial values. Polyexponential curve stripping is frequently used for the provision of initial estimates. It is demonstrated that under certain conditions conventional curve stripping yields biased estimates. A new iterative curve stripping technique is developed and is shown to be free of such bias. The two methods are compared using both simulated and real pharmacokinetic data.

Administration, Oral

Pharmacokinetic lag time estimation.

This note draws attention to a problem encountered when using the pharmacokinetic computer program CSTRIP for lag time estimation. The problem arises because data belonging to the lag phase is used for polyexponential parameter estimation. Simulated data are used to illustrate the effect on the fitted curve. A new curve stripping program JANA is shown to be free of this flaw.

Biometry

Sodium valproate stimulates the particulate form of glutamine synthetase in rat brain.

The anticonvulsant drug, sodium valproate, enhanced total activity of glutamine synthetase in cortical and cerebellar homogenates of the rat at concentrations of 25-50 mM, without significantly altering substrate affinity. This effect was due to a selective increase in the Vmax and substrate affinity of the enzyme in the particulate fraction. At the same concentration the drug caused little change in the Vmax of the cytosolic enzyme, although the substrate affinity was reduced. These effects cannot be attributed to isozymes of glutamine synthetase as only one form could be demonstrated by ion-exchange chromatography or electroblotting with antibodies to glutamine synthetase. This selective stimulation of particulate glutamine synthetase is suggested to be due to increases in membrane fluidity induced by the drug. The contribution of these effects to the mechanistic action of sodium valproate is discussed.

Animals

JANA: a new iterative polyexponential curve stripping program.

A new iterative polyexponential curve stripping technique for the provision of initial pharmacokinetic parameter estimates has been developed. Such estimates are required for nonlinear least-squares curve fitting. In contrast to conventional curve stripping, this new technique does not make any assumption about the relative magnitudes of the exponential rate constants. Hence, the parameter estimates which it provides are free of the bias which may arise in conventional curve stripping. A BASIC program called JANA has been developed to implement the new curve stripping procedure.

Computers