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Biomedical subjects

S Nichols

Publications and source records attributed to S Nichols.

At least 73 records · Page 4Linked to original sources

Inhibition of caffeine elimination by short-term ethanol administration.

Short-term ethanol ingestion has been shown to inhibit the metabolism of a number of drugs metabolized by cytochrome P-450 in both man and laboratory animals. However, the effects of short-term ethanol administration on the metabolism of cytochrome P-448-dependent drugs in man is unknown. Caffeine is a commonly used drug that is metabolized predominantly by a component of the hepatic microsomal mixed-function oxidase complex, known as cytochrome P-448. Therefore the elimination of caffeine given orally was studied in normal volunteers after receiving either orange juice or 0.8 gm/kg ethanol as a 25% solution in orange juice. Short-term administration of ethanol resulted in a significant decrease in the plasma clearance of caffeine from 96.6 +/- 13.4 ml/min to 60.7 +/- 10.5 (mean +/- S.E., p less than 0.05). There was also a corresponding significant increase in the elimination half-life of caffeine from 4.03 +/- 0.52 hr to 6.04 + 0.73 (mean + S.E., p less than 0.01). To determine whether the decrease in caffeine elimination was due to an inhibition of caffeine metabolism by ethanol or to an effect on caffeine absorption, caffeine disposition was studied in four healthy, mongrel dogs after intravenous administration. Each animal served as its own control. Caffeine clearance decreased significantly from a baseline value of 19.6 +/- 1.5 ml/min to 8.0 +/- 1.5 (mean +/- S.E., p less than 0.05) after administration of 3.0 gm/kg ethanol given orally 1 hr before intravenous caffeine injection. These results imply that short-term administration of ethanol inhibits the metabolism of caffeine, a predominantly cytochrome P-448-dependent substrate, in both man and dogs.

Adult↗

Victor Segalen.

Explore the source record for details and available documents.

France↗

'Don't take a chance': a public campaign to encourage the early reporting of breast symptoms.

As part of a study to evaluate health education about breast cancer, a campaign to encourage the early reporting of breast symptoms was organised jointly by Community Medicine, University of Southampton and Southampton Health Education Service. A thorough account of all aspects of the preparation and implementation of the campaign is presented. It is hoped that other organisations, considering a similar campaign, could utilise the materials specially produced to convey our message and benefit from our experiences.

Anxiety↗

Enhanced cell killing through the use of cell kinetics-directed treatment schedules for two-drug combinations in vitro.

Kinetics-directed drug treatment schedules were tested in Chinese hamster ovary cells. Ten hr after treatment with 1,2:5,6-dianhydrogalactitol (DAG) (at a dose lethal to less than 5% of the cells), a 150% enrichment of cells into the S phase of the cell cycle was observed. This blockade in S phase was reversible and was followed at 18 hr after an exposure to DAG by a 200% increase in the fraction of cells in the G2-M phases of the cell cycle. Bleomycin, known to be most effective against G2 + M cells, had the greatest effect on cell killing when administered at that time. Rapid analysis by flow microfluorometry techniques was used to determine the DAG-induced kinetics changes, thus allowing treatment with the second drugs at the most opportune time. The DAG-induced kinetics changes were also demonstrated in a line of human adenocarcinoma of the stomach in vitro and in Ehrlich ascites tumor cells in vivo. In all cases, the enrichment of cells into S phase was reversible at the doses used and was followed by a reversible blockade in G2-M.

Adenocarcinoma↗

Dual system of intestinal thiamine transport in humans.

The transport of thiamine across the intestine has been characterized in rats but has not been adequately studied in humans. To determine the kinetics of thiamine intestinal transport directly in humans, mucosal tissues were obtained during routine endoscopy from normal-appearing sites at the second portion of the duodenum. With 3H-dextran as the marker of adherent volume, the uptake of 14C-thiamine hydrochloride by the excised mucosa was measured in vitro. By this method thiamine uptake was linear with tissue weight and with incubation time up to 5 min. Results showed that at low thiamine concentrations (0.2 to 2.0 microM), uptake was saturable whereas at high concentrations (5 to 50 microM), uptake was linear with thiamine concentrations. Pyrithiamine, anoxia, N-ethylmaleimide, and replacement of sodium chloride by mannitol reduced the uptake of 0.5 microM thiamine by 42%, 37%, 32% and 35%, respectively (p less than 0.05) but had no effect on the uptake of 20 microM thiamine. These data suggest that, as in the rat, the intestinal transport of thiamine in humans proceeds by a coexistent dual system. At physiologic concentrations, thiamine is transported primarily by an energy-requiring, sodium-dependent active process, whereas at higher pharmacologic concentrations thiamine uptake is predominantly a passive process.

Biological Transport, Active↗

Changes in DNA distributions and ploidy of CHO cells as a function of time in culture.

Chinese hamster ovary (CHO) cells maintained in continuous culture for 3 to 5 months may undergo subtle changes in drug sensitivity response, growth kinetics, plating efficiencies, et cetera. Our studies done independently in two different laboratories, using flow cytometry, indicate that the DNA histogram patterns change at about 11 wk, from populations with an approximate diploid DNA content to populations also composed of triploid and tetraploid cells. Chromosome counts also change from distributions of 21 to 22 to populations of cells having 21 to 22, 34 to 35 and 44 to 46 chromosomes. These alterations occur earlier (at 8 to 9 wk) in cell populations previously treated with anticancer drugs.

Animals↗

Management of female breast disease by Southampton general practitioners.

One hundred and two Southampton general practitioners were interviewed about female breast disease. There was agreement about clinical management and the need to both teach and promote breast self-examination. The general practitioners, however, were divided as to whether any breast screening facilities were needed in Southampton. Records kept by the general practitioners of women seen with breast symptoms showed that one-quarter of all new episodes were referred to hospital at the first visit. That the general practitioners considered early diagnosis to be important was made evident from a number of the results. This attitude is encouraging in view of the evidence showing that long-term survival may be greater when delays are shorter.

Attitude of Health Personnel↗