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Biomedical subjects

P Coen

Publications and source records attributed to P Coen.

9 recordsLinked to original sources
PubMed2001

A centuries-long epidemic of scrapie in British sheep?

The apparent persistence of scrapie in British sheep for more than 250 years is difficult to explain. Susceptibility to scrapie is associated with particular alleles at a single locus, the PrP gene. As the only known effect of these alleles is to confer susceptibility to a fatal disease, natural selection is expected to reduce their frequency, as has been observed in practice during scrapie outbreaks in single sheep flocks. Susceptibility alleles, and hence scrapie itself, are therefore expected to become rare, yet the disease remains widespread. We suggest that the paradox of scrapie's persistence can be explained by the exceptionally long time-scales inherent in the epidemiology of the disease. It is proposed that scrapie should be regarded as epidemic in British sheep but, unlike more familiar epidemics, which have time-scales of months or years, the scrapie epidemic has a time-scale of centuries. This interpretation implies that scrapie should eventually disappear from the sheep population.

Animals↗
PubMed1999

Population dynamics of scrapie in a sheep flock.

A detailed analysis of an outbreak of natural scrapie in a flock of Cheviot sheep is described. A total of 137 cases was reported over 13 years among 1307 sheep born into the flock. The epidemiology of scrapie can only be understood with reference to sheep demography, the population genetics of susceptibility to scrapie, pathogenesis during a long incubation period, and the rate of transmission (by both vertical and horizontal routes), all of which interact in complex ways. A mathematical model incorporating these features is described, parameter values and model inputs are derived from available information from the flock and from independent sources, and model outputs are compared with the field data. The model is able to reproduce key features of the outbreak, including its long duration and the ages of cases. The analysis supports earlier work suggesting that many infected sheep do not survive to show clinical signs, that most cases arise through horizontal transmission, and that there is strong selection against susceptible genotypes. However, important aspects of scrapie epidemiology remain poorly understood, including the possible role of carrier genotypes and of an environmental reservoir of infectivity, and the mechanisms maintaining alleles giving susceptibility to scrapie in the sheep population.

Alleles↗
PubMed1993

Single- and multiple-dose pharmacokinetics of Nicoderm (Nicotine Transdermal System).

The pharmacokinetics and tolerability of single and multiple applications of Nicotine Transdermal Systems (NTS), designed to deliver 14 mg of nicotine per 24 hours, were investigated in 20 healthy adult male smokers. After a single application, mean Cmax and tmax for plasma nicotine were 12.2 ng/mL and 4.4 hours, respectively. Plasma nicotine concentrations rose rapidly and then remained steady between 12 and 24 hours after application. The apparent nicotine half-life (t1/2) after system removal was 3.2 hours. Steady state was attained by the second day of multiple application, and mean steady-state nicotine Cavg was 25% higher on day 5 compared with the first NTS application. Steady-state plasma cotinine was reached by the fourth day of multiple application and, as with nicotine, Cavg and Cmax increased, tmax decreased, and t1/2 did not change compared with single application. The mean ratios of cotinine-to-nicotine area under the curve (AUC) values for single and multiple NTS applications were 14.0 and 15.8, respectively. The pharmacokinetics of nicotine and cotinine were linear between single and multiple NTS applications. The nicotine transdermal systems were generally well tolerated.

Administration, Cutaneous↗
PubMed1991

Effect of food on bioavailability of pseudoephedrine and brompheniramine administered from a gastrointestinal therapeutic system.

The purpose of this study was to determine how a high-fat meal affects the delivery and absorption of pseudoephedrine and brompheniramine maleate when delivered from a gastrointestinal therapeutic system (GITS). This study was a randomized, complete crossover trial with 12 healthy male volunteers who were given single doses of the 24-h GITS under fed and fasted conditions. Pharmacokinetic parameters for both drugs were comparable between fed and fasted treatments, except for a shorter time to maximum concentration of pseudoephedrine for fed subjects (p = 0.002). Bioavailability of pseudoephedrine was 91% for fed relative to fasted treatment; for brompheniramine it was 89%. These results indicate that codelivery of the two drugs from the GITS is reliable and prolonged, and that the resulting absorption of pseudoephedrine and brompheniramine is minimally affected by food.

Adult↗
PubMed1987

The accuracy and precision of an open-circuit system to measure oxygen consumption and carbon dioxide production in neonates.

We measured the oxygen consumption, carbon dioxide production, and respiratory quotient during the combustion of a known mass of anhydrous ethanol and methanol to assess the accuracy of an open-circuit flow-through system. Continuous measurements were made of the mass of alcohol burned, the velocity of gas flow through the apparatus, and simultaneous measurements of the fractional concentration of oxygen, carbon dioxide and nitrogen of the inlet and outlet gas using paramagnetic oxygen analyzer, infrared carbon dioxide meter, and mass spectrometer. Standard respiratory and stoichiometric equations were used to calculate the oxygen consumption, carbon dioxide production and RQ for the mass of absolute alcohol combustion per unit time. In a series of 12 consecutive laboratory experiments (on 7 days), the measured values of gas exchange (similar to the rate of respiratory gas exchange by an infant of 1-4 kg) were in agreement within 5% of the true values for ethanol and methanol combustion, confirming the validity of the open-circuit method. The paramagnetic oxygen analyzer and the mass spectrometer gave similar oxygen consumption results and differed very little when the rate of absolute alcohol combustion was used to quantify the accuracy of the complete measurement system. A positive measurement error was observed for the carbon dioxide production results from both the IR meter and mass spectrometer, with the result that the respiratory quotient measurements were 3.4-4.7% higher than the true value. The mass spectrometer gave more precise oxygen consumption results, whereas smaller variance of carbon dioxide production measurements was observed using the infrared CO2 meter.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Dioxide↗
PubMed1982

Long-term lithium carbonate therapy causes hyperparathyroidism.

Twelve patients taking lithium carbonate for two to 13 years were compared with age- and sex-matched controls to determine whether long-term lithium carbonate therapy is associated with alterations in calcium metabolism. As a group and individually, patients had significantly higher levels of serum total calcium, ionized calcium, and parathyroid hormone. When compared with serum calcium levels, patients' parathyroid hormone levels were significantly more likely than those of controls to indicate hyperparathyroidism. Lithium carbonate-induced mild hyperparathyroidism appears to be more common than had previously been suspected.

Adult↗