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Biomedical subjects

N Barton

Publications and source records attributed to N Barton.

52 records · Page 3Linked to original sources
PubMed1986

Intrachromosomal gene conversion, linkage, and the evolution of multigene families.

The evolution of the probabilities of genetic identity within and between tandemly repeated loci of a multigene family is investigated analytically and numerically. Unbiased intrachromosomal gene conversion, equal crossing over, random genetic drift, and mutation to new alleles are incorporated. Generations are discrete and nonoverlapping; the diploid, monoecious population mates at random. Under the restriction that there is at most one crossover in the multigene family per individual per generation, the dependence on location of the probabilities of identity is treated exactly. In the "homogeneous" approximation to this "exact" model, end effects are disregarded; in the "exchangeable" approximation, to which all previous work was confined, all position dependence is neglected. Numerical results indicate that the exchangeable and homogeneous models are both qualitatively correct, the exchangeable model is sometimes too inaccurate for quantitative conclusions, and the homogeneous model is always more accurate than the exchangeable one and is always sufficiently accurate for quantitative conclusions.

Female↗
PubMed1986

Anatomical variations of the extensor pollicis brevis.

Sixteen arms in eight cadavers were dissected. The extensor pollicis brevis followed the description given in standard anatomy texts in only three out of the sixteen arms. Four out of the eight cadavers showed asymmetry of the extensor pollicis brevis between their two sides.

Arm↗
PubMed1986

The barrier to genetic exchange between hybridising populations.

Suppose that selection acts at one or more loci to maintain genetic differences between hybridising populations. Then, the flow of alleles at a neutral marker locus which is linked to these selected loci will be impeded. We define and calculate measures of the barrier to gene flow between two distinct demes, and across a continuous habitat. In both cases, we find that in order for gene flow to be significantly reduced over much of the genome, hybrids must be substantially less fit, and the number of genes involved in building the barrier must be so large that the majority of other genes become closely linked to some locus which is under selection. This conclusion is not greatly affected by the pattern of epistasis, or the position of the marker locus along the chromosome.

Alleles↗
PubMed1985

The energy cost of aerobic exercise in fed and fasted normal subjects.

It has been claimed that there is a prolonged thermogenic effect of aerobic exercise although the evidence is by no means conclusive. We have therefore studied the thermogenic effect of moderate aerobic exercise in the fasted and fed state in four lean subjects during weight maintenance. Exercise was performed at a constant rate on a bicycle ergometer during the initial 20 min for four successive hours. The first two exercise periods were in the fasted state while the last two followed an 800 kcal (3.4 MJ) mixed meal. Oxygen uptake increased 22% over the 165 min after the meal on rest days (p less than 0.001). There was a significant but similar elevation of mean O2 uptake during 40 min postexercise by 13.6% in both the fasted (p less than 0.001) and fed state (p less than 0.001). Sixty minutes after ceasing exercise mean O2 uptake was not different from preexercise levels (p greater than 0.05). We conclude that there is no prolonged thermogenic effect of moderate repeated aerobic exercise in weight-maintaining lean subjects. In addition there was no interaction between exercise and dietary induced thermogenesis.

Adult↗
PubMed1985

High-pressure liquid chromatographic methods for determining arabinosyladenine-5'-monophosphate, arabinosyladenine, and arabinosylhypoxanthine in plasma and urine.

New high-pressure liquid chromatographic methods for determining concentrations of arabinosyladenine (Ara-A), its 5'-monophosphate (Ara-AMP), and arabinosylhypoxanthine (Ara-H) in plasma and urine are presented. A fluorescence detector is used for Ara-A and Ara-AMP, which are first converted to highly fluorescent derivatives with chloroacetaldehyde. This increases sensitivity greatly over previous methods. The sensitivities of the methods (in micrograms per milliliter) are as follows: in plasma, Ara-AMP, 0.002; Ara-A, 0.0015; and Ara-H, 0.35; and in urine, 9 times these values, respectively. Drug concentration data are also presented, which were obtained after doses of Ara-AMP were given intramuscularly to two patients treated with this drug for severe herpes zoster. One patient was given 13 mg of Ara-AMP per kg of body weight once daily, and the other was given 6.5 mg/kg twice daily. Peak Ara-AMP and Ara-A levels in plasma occurred within 1 h after the doses, and neither exceeded 2 micrograms/ml. Ara-AMP and Ara-A concentrations in plasma fell to less than 0.01 micrograms/ml in both patients by 4 to 6 h after the doses. Peak Ara-H concentrations in plasma occurred within 1 to 2 h after doses and were 21 micrograms/ml in patient 1 and 2. The highest concentration of Ara-AMP in urine was 0.09 micrograms/ml. The highest Ara-A concentration in urine was 62 micrograms/ml, and the highest Ara-H concentration in urine was 1,080 micrograms/ml. An interfering substance of unknown nature, cochromatographing with Ara-H, was encountered sporadically in urine samples. An algorithm based on differential spectrophotometry to identify and correct for this problem is described. Estimates of the renal clearances of Ara-AMP, Ara-A, and Ara-H are also given.

Arabinonucleosides↗
PubMed1984

Infections caused by herpes simplex virus in the immunocompromised host: natural history and topical acyclovir therapy.

Sixty-three immunocompromised patients with infections caused by herpes simplex virus were evaluated in a double-blind, placebo-controlled study of topical acyclovir therapy; 33 patients received acyclovir and 30 received the placebo. The two populations of patients were balanced in terms of age, race, sex, underlying disease, preceding chemotherapy, and site, size, and duration of lesions. Acyclovir recipients experienced an acceleration in the clearance of virus (P = .0006), the resolution of pain (P = .004), and the total healing of lesions (P = .038); median temporal differences between populations averaged six days for each of these three parameters. The surface area of herpetic lesions continued to enlarge in placebo recipients after entry into the trial; in contrast, lesion surface area decreased progressively during therapy in drug recipients. The speed of healing was influenced by lesion size. Patients with lesions of greater than or equal to 50 mm2 benefited most from therapy, particularly in terms of pain resolution and time to total healing (median differences between groups, eight days). Irrespective of underlying disease, sex, preceding chemotherapy, or age, acyclovir therapy was of clinical benefit. No adverse clinical or laboratory reactions were encountered.

Acyclovir↗
PubMed1982

Pharmacokinetics of acyclovir in humans following intravenous administration. A model for the development of parenteral antivirals.

Data are reported from three step-wise pharmacokinetic studies in 43 patients who received acyclovir. Dosage regimens began at 0.5 mg/kg administered as a single dose intravenously and were increased to 15 mg/kg per dose given three times daily for five days. All patients evaluated were immunocompromised by underlying disease or received cytolytic and/or cytotoxic therapy. Patients with virologically confirmed herpes simplex or zoster infections were assessed in the multiday, multidose pharmacokinetic trial. Postinfusion plasma concentrations of acyclovir declined in a biphasic manner such that the plasma-concentration time data were fitted by a two-compartment, open-model with zero-order input. The drug's half-life showed little variation with a mean of 3.16 +/- 0.20 hours. In both single-dose and multiple-dose studies there was dose proportionality with peak plasma levels and area under the plasma concentration-time curve indicating dose-independent pharmacokinetics. The kidney was the principal route of drug clearance with a mean recovery of 60 +/- 12 percent. Renal clearance exceeded creatinine clearance indicating renal tubular secretion of drug. No significant clinical or laboratory evidence of toxicity appeared. These studies provide a foundation for the evaluation of acyclovir in controlled trials.

Acyclovir↗
PubMed1982

Mucocutaneous herpes simplex virus infections in immunocompromised patients. A model for evaluation of topical antiviral agents.

Forty-three immunocompromised patients with progressive cutaneous herpes simplex virus infections were studied in a double-blind, placebo-controlled evaluation of topically applied acyclovir. Patients were randomized and 22 received acyclovir and 21 placebo; medications were applied four times daily for 10 days. Both study populations were balanced for all demographic characteristics. Acyclovir therapy resulted in no median differences in time to total healing compared with placebo responses, p = 0.13. However, those patients who received the acyclovir ceased shedding virus more rapidly, p less than 0.001, and lost pain more readily, p = 0.04, than placebo counterparts. Neither group experienced adverse effects. Because of the protracted nature of mucocutaneous herpes simplex infections in these patients, the immunocompromised host provides a good model for evaluation of topical antiviral therapy.

Acyclovir↗
PubMed1979

Acyclovir kinetics after intravenous infusion.

The disposition and safety of the antiviral drug acyclovir were studied in 14 subjects with advanced malignancies. Acyclovir was administered by a 1-hr intravenous infusion at doses of 0.5, 1.0, 2.5, and 5.0 mg/kg. At the end of infusion, mean peak plasma levels (+/- SEM), determined by radioimmunoassay, were 6.4 +/- 0.7, 12.1 +/- 2.3, 14.9 +/- 2.7, and 33.7 +/- 7.1 microM. The plasma concentration-time profiles could be described by a biexponential equation. The half-life of acyclovir in the slow disposition phase ranged from 2.2 to 5 hr and the drug was detected in the plasma for at least 18 hr after infusion. The total body clearance ranged from 117 to 396 ml/min/1.73 m2. A proportionality between area under the curve and dose suggests that acyclovir exhibits dose-independent kinetics in the dose range studied. There was wide variation in cumulative urinary excretion of unchanged drug, ranging from 30 to 69% of the dose. From renal clearances of acyclovir, which were higher than creatinine clearances, it appears that both glomerular filtration and tubular secretion contribute to its renal excretion. Analysis of the urine by reverse-phase high-performance liquid chromatography revealed the presence of the metabolite 9-carboxymethoxymethylguanine. There was no indication of toxicity either clinically or from laboratory findings in any of the study subjects. This study demonstrates that in addition to selectivity and low toxicity, the kinetic profile and metabolic disposition of acyclovir make it an attractive candidate for therapy in a variety of herpes infections.

Aged↗
PubMed1977

Fractures of the phalanges of the hand.

A retrospective study has been made of 100 unselected adult finger fractures and a smaller group of similar injuries in children. The principles of treatment are reviewed, a simple practical classification of finger fractures suggested, and the treatment of each type described.

Adolescent↗