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Biomedical subjects

J A Clements

Publications and source records attributed to J A Clements.

At least 163 records · Page 9Linked to original sources

Data point weighting in pharmacokinetic analysis: intravenous paracetamol in man.

Compartmental analysis of plasma paracetamol concentrations following intravenous injection of 12 mg kg-1 in aqueous solution to normal subjects was performed using analogue and digital computer methods. Using a "simplex" non-linear optimization procedure, the pharmacokinetic parameters were found to be influenced considerably by the choice of the weighting factors (W1) attributed to individual data points. The plasma half-life of paracetamol varied by up to a seven-fold with the weighting factors selected. However, the predicted mean steady-state plasma concentrations were shown to be relatively little affected by the different weighting factors.

Acetaminophen↗

Studies on human sexual development. III. Fetal pituitary and serum, and amniotic fluid concentrations of LH, CG, and FSH.

Fetal sera (9-20 weeks fetal age, n = 80) and pituitary glands (9.5-20 weeks, n = 36) obtained from hysterotomy specimens, and amniotic fluids (amniocentesis; 8-40 weeks, n = 123) were assayed for FSH, LH (betaLH assay) and CG (betaCG assay). Results are expressed as mass of pure hormone. Prior to 12 weeks fetal age, pituitary, serum and amniotic fluid concentrations of LH and FSH were low or unmeasurable. In contrast, levels of CG in serum and in amniotic fluid were clearly measurable prior to 12 weeks. There was a definite CG peak at 11-14 weeks with levels up to 550 ng/ml in serum and 7400 ng/ml in amniotic fluid. Although LH levels began to rise at 12 weeks, when CG levels started to decline, serum levels of LH from 14-20 weeks in males (2-13 ng/ml) were still lower than the majority of CG levels at this time (6-115 ng/ml). These observations suggest that CG is the primary stimulus to the fetal Leydig cell which results in testosterone secretion (peak 11-17 weeks) and masculine differentiation of the genital tract. Significantly lower concentrations of both FSH and LH were observed in pituitary, serum and amniotic fluid between 12-20 weeks fetal age in males compared to females. This may be a result of feedback inhibition by the higher concentrations of testosterone in males at this time. Amniotic fluid FSH and LH concentrations correlated with their respective serum and pituitary values (P less than 0.01) indicating that amniotic fluid may provide a convenient index of fetal serum concentrations.

Amniotic Fluid↗

Isolation of disaturated phosphatidylcholine with osmium tetroxide.

A simple, rapid, inexpensive method for isolating disaturated phosphatidylcholine from adult rat lung has been devised. Total lipids are reacted with osmium tetroxide dissolved in carbon tetrachloride, and the disaturated phosphatidylcholine is isolated on a column of neutral alumina. More than 99% of the fatty acids in the phosphatidylcholine fraction are saturated and 94% of this material migrates as phosphatidylcholine on subsequent thin-layer chromatography.

Animals↗

Pulmonary effects of paraquat in the first day after injection.

To learn whether surface force changes precede the appearance of lung edema during experimental intoxication due to paraquat, we studied rats for 1 day following injection of 27 mg/kg iv. By 24 h, surface-active material recovered by lung lavage was decreased 32 percent, and changes in lung microsections and recoil pressure at half-deflation suggested decreased alveolar stability. Despite a 25 percent loss in overall body weight, lung weight increased more than 7 percent and protein concentration in lung lavage fluid increased by 158 percent. Lung edema was demonstrated morphologically as early as we could detect changes in surfactant or lung mechanical properties. Metabolic studies with lung tissue slices incubated with 4.5 times 10-4 M paraquat showed a fourfold increase in 14CO2 formed from (1-14C) glucose, but no significant change in 14CO2 form (6-14C) glucose, suggesting increased utilization of the pentose pathway for oxidation of glucose. (1-14C) Acetate oxidation was impaired slightly, but incorporation into lipid was decreased by 70 percent. we conclude that paraquat intoxication in the rat is not a suitable model for studying uncomplicated perturbation of the surfactant system.

Acetates↗

Ontogeny of tracheal fluid, pulmonary surfactant, and plasma corticoids in the fetal lamb.

We examined fetal plasma corticoids and flow rate, electrolyte composition, and surfactant content of tracheal fluid in chronic experiments with eight fetal lambs. From 120 to 148 days of gestation the rate of fluid production was 4.5 ml/kg per h, and there was no change in mean fluid sodium (147.8 meq/1), chloride (153.1 meq/1), calcium (2.2 mg/100 ml), and pH (6.23). Tracheal fluid potassium increased from 4.3 meq/1 at 120-130 days to 8.9 meq/1 at term, while plasma sodium, chloride, calcium, pH, and potassium were constant at 146.1 meq/1, 110.0 meq/1, 12.1 mg/100 ml, 7.39, and 4.0 meq/1, respectively. Plasma corticoids were less than 1.5 mug/100 ml total (0.3 mug/100 ml free) until 130 days, when they increased rapidly to 10.5 total (3.2 free) at 148 days. Surfactant was first detected in tracheal fluid between 124 and 133 days and its secretion increased rapidly after 135 days to a value of 125 mug/kg per h at 148 days. A sudden increase in fetal plasma corticoids does not seem to be the stimulus for appearance of surfactant in the lamb, although these hormones may induce the rapid accumulation of surfactant prior to delivery.

Adrenal Cortex↗

Surfactant in the lung and tracheal fluid of the fetal lamb and acceleration of its appearance by dexamethasone.

We measured tracheal fluid production rate and pulmonary surfactant flux in 12 sets of twin fetal lambs of 102 to 135 days' gestation. In nine of these sets we also measured surfactant flux and the concentration of saturated lecithin in the lungs before and during dexamethasone infusion into one of the twins. The average tracheal fluid flow rate was 3.25 ml/kg/hr (SD 1.6) and, relative to body weight, did not change between 103 and 135 days' gestation or during the infusion of dexamethasone. In untreated fetuses, surfactant was detected between 108 and 130 days and its flux gradually increased but remained less than 150mug/kg/hr at 135 days' gestation; the amount of disaturated lecithin in the lung relative to body weight increased 13-fold from 108 to 134 days. From these data we calculated that the minimal rate of synthesis of disaturated lecithin was increased about 4-fold by dexamethasone from 108 to 120 days; this enhancement fell to about 1.8-fold by 135 days. The rate of secretion of disaturated lecithin, as estimated by surfactant flux in tracheal fluid, was increased by dexamethasone throughout the interval of the study.

Animals↗

Dispersal of rabbit lung into individual viable cells: a new model for the study of lung metabolism.

This new enzymatic method disperses rabbit lung into morphologically intact, viable individual cells. The scattered cells constitute more than 50 percent of the original tissue. At least 90 percent of the cells exclude trypan blue from the nucleus. The dispersed lung cells consumed 6.2 microliters of oxygen per hour per milligram, dry weight. They incorporated [1-(14)C]palmitate into lecithin.

Animals↗