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Biomedical subjects

A Dunne

Publications and source records attributed to A Dunne.

At least 37 records · Page 2Linked to original sources
PubMed1997

Level A in vivo-in vitro correlation: nonlinear models and statistical methodology.

Some new nonlinear models for the relationship between the fraction of drug dose dissolved (absorbed) in vivo and that dissolved in vitro are described. The models are empirical in nature and are generalizations of the linear model that, at present, is the most commonly used model. The modeling approach is based on considering the time at which a drug molecule goes into solution (in vitro or in vivo) to be a random variable and relating the distribution functions using proportional odds, proportional hazards, and proportional reversed hazards models. The models are further extended by allowing the parameter that relates in vivo and in vitro to be a function of time. A statistical model for the data is developed and used as the basis for a statistical methodology for fitting these models. The methods are shown to be generalized linear mixed effects model (GLMM) methods. The models are fitted to some data sets, and the results demonstrate that these models have potential.

Models, Statistical↗
PubMed1995

Decision and detection limits for linear homoscedastic assays.

This paper focuses on the effect of estimating the calibration parameters on the decision and detection limits for linear homoscedastic assays. Assay decision and detection limits are defined. For linear homoscedastic assays expressions for these limits are derived when the calibration parameters are known and unknown. These expressions, together with others previously reported in the literature, are used to calculate limits for a particular example of a cyclic AMP assay. The various methods of computing decision and detection limits are compared in a simulation study. The results demonstrate the importance of taking into consideration the variation in the estimators of the calibration parameters.

Chemistry, Clinical↗
PubMed1995

D2 receptor antagonists do not modify guanine nucleotide-sensitive interactions between dopamine and D1 dopamine receptors under in vitro conditions.

This study investigated possible D1/D2 interactions in rat and bovine striatal tissue by examining the effects of D2 antagonists on the action of dopamine at D1 dopamine receptors. In addition, the extent to which D2 antagonists may induce an agonist low-affinity state of the D1 receptor was evaluated in comparison with the effects of the guanine nucleotide analogue 5'-guanylyl-imidodiphosphate [Gpp(NH)p]. In saturation experiments dopamine caused a dose-dependent decrease in rat striatal and bovine caudate D1 receptor density. This effect of dopamine, which has been shown to be sensitive to Gpp (NH)p, was not altered by pretreatment with either of the selective D2 antagonists eticlopride (200 nM) or domperidone (200 nM). Results from displacement experiments show that the affinity of dopamine for D1 receptors, and the proportion of receptors in an agonist high-affinity state, are reduced by Gpp(NH)p (100 microM) but not by eticlopride. A molar excess of dopamine (100 microM) promotes the dissociation of (+/-)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-o l ([3H]SCH 23390) from rat striatal D1 receptors at a rate that is significantly slower than when dissociation is initiated using 1 microM piflutixol. After pretreament with Gpp(NH)p, [3H]SCH 23390 dissociation induced by dopamine occurred at an even slower rate. Pretreatment with eticlopride had no effect on the dopamine-induced rate of [3H]SCH 23390 dissociation. These results indicate that all experimental approaches detected dopamine effects at D1 receptors that are Gpp(NH)p sensitive and D2 antagonist insensitive and provide no evidence to support a D1/D2 link operating at the receptor level.

Animals↗
PubMed1995

A randomized, double-blind, placebo-controlled trial of systemically administered interferon-alpha, -beta, or -gamma in combination with cryotherapy for the treatment of condyloma acuminatum.

One hundred fifty-two patients were enrolled in a study to evaluate 3 interferon (IFN) preparations used in combination with cryotherapy for treatment of anogenital warts. Subjects received subcutaneous injections (2 x 10(6) units/m2) of IFN-alpha n1, -beta, -gamma or placebo 3 times a week for 6 weeks and cryotherapy with liquid nitrogen. Subjects were followed < or = 1 year. Among patients followed > or = 12 weeks, two-thirds had a complete response. No significant differences in rates of complete response (P = .37) or reappearance of a wart at the initial site (P = .20) were noted among the treatment groups. However, patients who received IFN-beta or -gamma developed new warts at a significantly lower frequency (P = .02). IFN administration was associated with side effects but was well tolerated. IFN-beta was the least toxic of the 3 preparations and had the best therapeutic ratio.

Adult↗
PubMed1993

Statistical moments in pharmacokinetics: models and assumptions.

The modelling basis of statistical moments in pharmacokinetics is considered and the associated assumptions and restrictions highlighted. Both deterministic and statistical models are described and they are seen to give identical results on the basis of equivalent assumptions. It is shown that it is not necessary to assume that all kinetic processes are first order and that some of the pharmacokinetic parameters may be dependent on the dose of administered drug and on the route of administration.

Models, Statistical↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗