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Biomedical subjects

T Jones

Publications and source records attributed to T Jones.

At least 181 records · Page 10Linked to original sources
PubMed1997

One-week therapy with twice-daily butenafine 1% cream versus vehicle in the treatment of tinea pedis: a multicenter, double-blind trial.

BACKGROUND: Butenafine hydrochloride, a benzylamine derivative with potent antifungal activity, has been used in Japan to treat superficial fungal diseases. OBJECTIVE: We evaluated the safety and efficacy of twice-daily butenafine versus its vehicle in the treatment of interdigital tinea pedis in a multicenter, randomized, double-blind, parallel-group trial. METHODS: A total of 402 patients with interdigital tinea pedis and a positive potassium hydroxide examination were enrolled. Of the 271 patients who had culture-confirmed tinea pedis and were assessed for efficacy, 132 applied butenafine and 139 applied vehicle twice daily for 1 week. Patients were assessed for mycologic cure, effective treatment, overall cure, and mycologic/clinical cure. RESULTS: The rates of all four end points were significantly higher with butenafine than with vehicle 5 weeks after treatment ended. Rates of mycologic cure and effective treatment with butenafine were significantly higher than with vehicle at cessation of treatment. Adverse events to treatment occurred in less than 1% of patients treated with butenafine and 2% of patients who applied vehicle. CONCLUSION: Butenafine applied twice daily for 1 week is highly effective in treating interdigital tinea pedis.

Administration, Topical↗
PubMed1997

Potent immunogenic short linear peptide constructs composed of B cell epitopes and Pan DR T helper epitopes (PADRE) for antibody responses in vivo.

Induction of humoral immune responses against protein antigen requires that two independent signals be delivered to B cells. It is currently assumed that simple monovalent synthetic peptides would not be effective immunogens for antibody responses because they would not be anticipated to effectively generate the necessary signals unless conjugated to a complex carrier system. In this study, the immunogenicity of short linear peptide constructs comprising Plasmodium vivax B cell epitopes (PVB) and non-natural Pan-DR T helper cell epitopes (PADRE) was assessed in mice and compared to other types of antigen constructs. The 33-residue PADRE-PVB linear constructs were highly immunogenic and induced responses comparable to those obtained with the multiple antigen peptides (MAP) constructs, both in terms of absolute titers and quality of antibody responses. The anti-PVB antibody responses were of long duration, composed mostly of IgG and reactive with intact sporozoites. The PADRE-PVB constructs were immunogenic when formulated in adjuvants such as Alum and Montanide ISA 51 underlining the relevance of these findings for vaccine development.

Adjuvants, Immunologic↗
PubMed1997

Enhanced myocardial 18F-2-fluoro-2-deoxyglucose uptake after orthotopic heart transplantation assessed by positron emission tomography.

OBJECTIVES: We sought to assess the relation between glucose metabolism, myocardial perfusion and cardiac work after orthotopic heart transplantation. BACKGROUND: The metabolic profile of the transplanted cardiac muscle is affected by the lack of sympathetic innervation, impaired inotropic function, chronic vasculopathy, allograft rejection and immunosuppressive therapy. In relation to myocardial perfusion and cardiac work, glucose metabolism has not previously been studied in heart transplant recipients. METHODS: Regional myocardial blood flow (ml.min-1.g-1) and 18F-2-fluoro-2-deoxyglucose (18FDG) uptake rate (ml.s-1.g-1) were measured after an overnight fast in 9 healthy male volunteers (mean age +/- SD 32 +/- 7 years) and in 10 male patients (mean age 50 +/- 10 years) who had a nonrejecting heart transplant, normal left ventricular function and no angiographic evidence of epicardial coronary sclerosis. Measurements were made by using dynamic positron emission tomography (PET) with 15O-labeled water and 18FDG, respectively. Heart rate and blood pressure were also measured for calculation of rate-pressure product. RESULTS: 18FDG uptake was similar in all heart regions in the patients and volunteers (intrasubject regional variably 12 +/- 8% and 16 +/- 12%, respectively, p = 0.51). Regional myocardial blood flow was similarly evenly distributed (intrasubject regional variability 14 +/- 10% and 12 +/- 8%, respectively, p = 0.67). Mean 18FDG uptake and myocardial blood flow values for the whole heart are given because no regional differences were identified. 18FDG uptake was on average 196% higher in the patients than in the volunteers (2.90 +/- 1.79 x 10(-4) vs. 0.98 +/- 0.38 x 10(-4) ml.s-1.g-1, p = 0.006). Regional myocardial blood flow and rate-pressure product were similarly increased in the patient group, but by only 41% (1.14 +/- 0.3 vs. 0.81 +/- 0.13 ml.min-1.g-1, p = 0.008) and 53% (11,740 +/- 2,830 vs. 7,689 +/- 1,488, p = 0.001), respectively. CONCLUSIONS: 18FDG uptake is homogeneously increased in normally functioning nonrejecting heart transplants. This finding suggests that glucose may be a preferred substrate in the transplanted heart. The magnitude of this observed increase is significantly greater than that observed for myocardial blood flow or cardiac work. In the patient group, the latter two variables were increased to a similar degree over values in control hearts, indicating a coupling between cardiac work load and myocardial blood flow. The disproportionate rise in 18FDG uptake may be accounted for by inefficient metabolic utilization of glucose by the transplanted myocardium or by the influence of circulating catecholamines, which may stimulate glucose uptake independently of changes in cardiac work load.

Adult↗
PubMed1997

Mutual interaction between remacemide hydrochloride and phenytoin.

A randomised, double-blind, placebo-controlled crossover study of add-on remacemide hydrochloride was carried out in epilepsy patients being treated with phenytoin (PHT) monotherapy. Eleven patients were recruited, ten of whom completed the study. Plasma concentration profiles of PHT, remacemide, and its active desglycinyl metabolite (ARL12495XX) were determined following single and multiple dosing with remacemide hydrochloride. Following 14 days' treatment with remacemide hydrochloride 300 mg twice daily, the mean AUC of PHT was increased by 11.5% (P = 0.33), Cmax by 13.7% (P = 0.32) and Cmin by 22.2% (P = 0.12) over placebo. There was an increase in trough concentrations of PHT averaging 20% during active treatment compared with placebo (P = 0.01). No symptoms of PHT toxicity were reported by any patient. There was no evidence of autoinduction of remacemide metabolism. However, average concentrations of remacemide and its active metabolite in PHT-treated patients were around 40 and 30% lower, respectively than in healthy volunteers previously receiving the same dose of remacemide hydrochloride. Thus, remacemide hydrochloride has a small inhibitory effect on PHT metabolism, which itself induces that of remacemide and its active metabolite. This mutual interaction is predictable and modest and should not present a barrier to their clinical use in combination.

Acetamides↗
PubMed1997

Carbon-11 labelling of the antitumour agent N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) and determination of plasma metabolites in man.

The potential anti-cancer agent N-[2-(dimethylamino)ethyl] acridine-4-carboxamide, DACA has been labelled with carbon-11. N-[2-11C-methyl]DACA was produced in 73% radiochemical yield from [11C]iodomethane in 40 min from EOB. The average radiochemical yield was 3.2 GBq with specific radioactivity of 41.5 GBq mumol-1 at EOS, corresponding to 24 micrograms of stable DACA. The position of labelling was confirmed by co-labelling with [11/13C]iodomethane. PET studies in patients have been performed prior to Phase I trial of DACA and during Phase I trial of DACA. Analysis of serial plasma samples showed that the metabolism of N-[2-11C-methyl]DACA is rapid and extensive in patient plasma.

Acridines↗
PubMed1997

Lack of pharmacokinetic interaction between remacemide hydrochloride and sodium valproate in epileptic patients.

A randomized, double-blind, placebo-controlled cross-over study of adjuvant treatment with remacemide hydrochloride was carried out in 17 patients taking sodium valproate (VPA) as monotherapy. Plasma concentration profiles of VPA, remacemide, and its active desglycinyl metabolite (ARL12495XX) were determined following single (300 mg) and multiple dosing (150 or 300 mg twice daily) of remacemide hydrochloride for 14 days with a 300-mg final dose. Central nervous system side-effects were more common at the higher dose, which prompted dosage reduction to 150 mg twice daily for subsequent patients partway through the study. The mean area under the concentration-time curve, peak concentration and pre-dose concentration of VPA were unchanged by remacemide hydrochloride in three patients on the higher and in 10 patients on the lower dose of remacemide. The pharmacokinetic parameters of remacemide and its active metabolite in the VPA-treated patients were similar to those described previously in healthy volunteers. Thus, remacemide hydrochloride does not interfere with the pharmacokinetics of VPA and vice versa.

Acetamides↗
PubMed1997

An in vitro study on the effect of branch points on the stability of coronary artery flow.

Empirical correlations for the onset of turbulence in pulsatile flow through a straight tube and a 45 degrees T-bifurcation are presented. We pumped three different test fluids of kinematic viscosity 0.008-0.035 cm2 s-1 through four straight tubes 0.4-3.0 cm in diameter and three 45 degree T-bifurcations 0.45-2.2 cm in diameter. A Scotch yoke mechanism provided an oscillatory sine wave flow component of known stroke volume and frequency. To determine transition to turbulence, we adjusted the mean flow independently until we detected signal instabilities from hot film or electrochemical wall shear stress probes. The critical peak Reynolds number was found to correlate with two independent dimensionless groups: the Womersley parameter and the Strouhal number. We derived power low functions of these groups to provide an accurate and convenient method of predicting transition in both straight and bifurcating tubes. When compared to pulsatile flow through the straight tube, the presence of flow separation within the 45 degrees T-bifurcation induced flow instabilities at lower values of the peak Reynolds number. The correlation for the 45 degrees T-bifurcation is also a suitable model for predicting transition at coronary branch points, which we previously studied in an in vitro pulse duplicator. Flow instabilities at coronary branch points may play an important role in atherogenesis.

Arteriosclerosis↗
PubMed1997

Three-dimensional performance of a small-diameter positron emission tomograph.

Recently, the initial 2D physical characterization of a small-diameter positron emission tomograph, designed specifically for scanning of small laboratory animals, was reported. The physical characteristics of the tomograph operating in 3D mode have now been measured and compared to those obtained in 2D mode. In 3D, the transaxial resolution was measured as 2.4 +/- 0.1 mm full width at half maximum (FWHM) and 6.7 +/- 1.1 mm full width at tenth maximum (FWTM) at the centre of the transaxial field of view (FOV). These values degraded to 4.5 +/- 0.3 mm (tangential) and 6.6 +/- 0.3 mm (radial) FWHM and 10.6 +/- 1.6 mm (tangential) and 11.2 +/- 2.1 mm (radial) FWTM, respectively, at a distance of 40 mm from the centre of the transaxial FOV. The axial resolution was measured as 4.6 +/- 0.1 mm FWHM and 15.0 +/- 0.5 mm FWTM at the centre of the transaxial FOV, increasing to 5.0 +/- 0.1 mm FWHM and 18.8 +/- 3.7 mm FWTM at a radial distance of 40 mm from the centre of the transaxial FOV. These resolutions are similar to those obtained for the tomograph operating in 2D mode. The sensitivity of the tomograph operating in 3D was 4.31 x 10(4) counts s-1 MBq-1 at 250-850 keV compared to 0.995 x 10(4) counts s-1 MBQ-1 in 2D at the same energy thresholds. In this energy window the noise equivalent count rate peaked at 4.1 x 10(4) counts s-1, compared to 1.03 x 10(4) counts s-1 in 2D. A scatter fraction of 30.2% at 250-850 keV was measured for a 18F line source centered in a 60 mm diameter water filled phantom in 3D, compared to 31.0% in 2D for the same scanning geometry and energy thresholds. A comparison was made between 2D and 3D kinetic analyses for a group of five anaesthetized rats scanned using [11C] SCH 23390, a marker of dopamine D1 receptors. The integrity of the results was maintained between 2D and 3D data sets, though in 3D there was a significant reduction in the standard error of the fitted parameter. The results demonstrate that, with regard to sensitivity, there are significant gains in the physical performance of this tomograph when operating in 3D compared to 2D mode and that the quantification of PET studies of small animals using the 3D data reflects this.

Animals↗
PubMed1997

Analysis of dynamic radioligand displacement or "activation" studies.

We present a simple way of assessing dynamic or time-dependent changes in displacement during single-subject radioligand positron emission tomography (PET) activation studies. The approach is designed to facilitate dynamic activation studies using selective radioligands. These studies are, in principle, capable of characterising functional neurochemistry by analogy with the study of functional neuroanatomy using rCBF activation studies. The proposed approach combines time-dependent compartmental models of tracer kinetics and the general linear model used in statistical parametric mapping. This provides for a comprehensive, voxel-based and data-led assessment of regionally specific effects. The statistical model proposed in this paper is predicated on a single-compartment model extended to allow for time-dependent changes in kinetics. We have addressed the sensitivity and specificity of the analysis, as it would be used operationally, by applying the analysis to 11C-Flumazenil dynamic displacement studies. The activation used in this demonstration study was a pharmacological (i.v. midazolam) challenge, 30 min after administration of the tracer. We were able to demonstrate, and make statistical inferences about, regional increases in k2 (or decreases in the volume of distribution) in prefrontal and other cortical areas.

Activation Analysis↗
PubMed1997

The ecology of echo.

Echo is a generic ecosystem model in which evolving agents are situated in a resource-limited environment. The Echo model is described, and the behavior of Echo is evaluated on two well-studied measures of ecological diversity: relative species abundance and the species-area scaling relation. In simulation experiments, these measures are used to compare the behavior of Echo with that of a neutral model, in which selection on agent genotypes is random. These simulations show that the evolutionary component of Echo makes a significant contribution to its behavior and that Echo shows good qualitative agreement with naturally occurring species abundance distributions and species-area scaling relations.

Biological Evolution↗
PubMed1997

Pulmonary and cardiac beta-adrenoceptor density in vivo in asthmatic subjects.

To examine whether there is a primary deficit in beta-adrenoceptor density in asthma, pulmonary and cardiac beta-receptor density was determined in vivo with positron emission tomography (PET) in 10 male asthmatic subjects (36 +/- 8 yr of age) and compared with that in 30 age-matched normal male subjects (36 +/- 8 yr of age). Pulmonary beta-receptor density was 10.3 +/- 1.8 pmol/g tissue for the asthmatic group and 10.9 +/- 1.9 for the normal group. Cardiac beta-receptor density was 9.1 +/- 3.3 pmol/g for the asthmatic group and 8.8 +/- 2.3 pmol/g for the normal group. There was no difference in either pulmonary or cardiac beta-receptor density between the two groups. In addition, an inverse relationship was observed between FEV1 % predicted and pulmonary beta-receptor density in asthmatic subjects. In conclusion, beta-receptor numbers are normal in untreated asthmatic subjects.

Adult↗
PubMed1997

Demonstration of clomipramine and venlafaxine occupation at serotonin reuptake sites in man in vivo.

We describe the use of 11CRTI-55 and the Multiple Objects Coincidences Counter (MOCC) to detect in-vivo binding to peripheral serotonin reuptake sites (left chest comprising platelet and lung serotonin reuptake sites) in man. Displacement and preloading experiments with clomipramine and venlafaxine in two healthy volunteers demonstrated that 11CRTI-55 binding is decreased in a dose-dependent fashion by both these drugs which bind to the serotonin transporter. In addition parallel data from the total head curve (representing 11CRTI-55 binding to central serotonin and dopamine (DA) reuptake sites) suggest that prior blockade of the serotonin transporter may be a useful strategy to maximize radioactive counts in the head when measuring the DA transporter. The MOCC is likely to be useful to determine sequential indices of relative serotonin reuptake blockade in patients on treatment.

Adult↗
PubMed1997

Complex duplications at 6p22.1, 6p11.2, 5q13, 5p15.1 and 5p13 revealed by fluorescent in situ hybridisation.

A complex pattern of fluorescent in situ hybridisation (FISH) has been detected using PAC clones from the short arm of chromosome 6, proximal to the haemochromatosis gene at 6p22.1. Cross-hybridisation to 6p22.1, 6p11.2, 5q13, 5p15.1 and 5p13 was consistently detected with several PAC clones covering a genomic region greater than 200 kb. These results indicate that large sections of genomic DNA are shared by these 5 disparate chromosomal segments, indicative of large scale duplication events. These results were in part accounted for by the identification of several expressed sequence tags (ESTs).

Chromosomes, Human, Pair 5↗
PubMed1997

Empirical Bayes prediction of 305-day milk production.

A lactation curve described by an algebraic formula can be fitted by regression to the milk weights in the partial record of an individual lactation in progress; however, curves that are obtained in this manner do not provide useful predictions of milk production throughout the remainder of the lactation. This study examined the reasons for this failure and introduced a new empirical Bayes statistical method for fitting Wood's curve that was designed to provide good predictions of future production. The results of a comparison between predictions produced by the new method and predictions from Dairy Herd Improvement Association extension factors were quite favorable to the new method, which has advantages other than greater accuracy; the method does not require preparation of extension factor tables and can be readily adapted to individual herds. Comparisons revealed features of the Dairy Herd Improvement Association predictions that limit their usefulness for some herd management purposes.

Algorithms↗
PubMed1997

Malaria in a nonimmune population after extended chloroquine or primaquine prophylaxis.

Extended chemoprophylaxis against endemic malaria raises concern with regard to susceptibility after ceasing use of the drug. In this study, we measured attack rates of malaria among adult men for 28 weeks after they ended one year of prophylaxis using either weekly chloroquine (5 mg base/kg, n = 20), daily primaquine (0.5 mg base/kg, n = 30), or a placebo of primaquine (n = 41). The 28-week incidence densities, times to parasitemia, parasite densities, and symptoms of primary post-prophylaxis infections were not significantly different among the former primaquine, chloroquine, and placebo groups. However, the incidence of Plasmodium falciparum infection in the post-chloroquine group was significantly greater than in the post-primaquine group during the first (P = 0.03) and second (P = 0.02) months post-prophylaxis. Six of 10 primary P. falciparum and three of 10 P. vivax infections occurred in the former chloroquine group within one month after ending prophylaxis and the mean time to infection was 30-35 days. In contrast, only one P. falciparum and no P. vivax infections occurred during the first month after ending primaquine prophylaxis. The mean time to first parasitemia by either species of malaria parasite in this group was 72-77 days. There was no indication that daily use of primaquine for one year placed subjects at greater risk of malaria infection or to more severe clinical symptoms of malaria than subjects who had taken placebo or chloroquine, despite the potential for some degree of immunity to have been acquired in these latter two groups during the year-long prophylaxis period. The results do suggest that chloroquine suppressed P.falciparum infections until drug levels decreased, and that primaquine had effectively prevented the establishment of liver-stage parasites.

Antimalarials↗