David Sylwester

The effects of phenobarbital, chloral betaine, and glutethimide administration on warfarin plasma levels and hypoprothrombinemic responses in man

Ten male volunteers received phenobarbital, glutethimide, chloral betaine, and a placebo at bedtime for 3 week periods. Plasma warfarin levels and prothrombin times were determined after a single oral dose of warfarin prior to and immediately following placebo or hypnotic drug treatment. Glutethimide and phenobarbital lowered the plasma warfarin concentration and reduced the half‐life of warfarin by nearly 50 per cent. Chloral betaine had less effect but differed significantly from control values. Phenobarbital and glutethimide interfered with the hypoprothrombinemic effect of warfarin; chloral betaine and placebo did not. The findings suggest increased metabolic inactivation of warfarin by induction of liver microsomal enzymes.

Interaction of Commonly Prescribed Drugs and Warfarin

Abstract The recognition of drugs that interact with warfarin has clinical relevance because of potential serious reactions as a result of the complexities of multiple drug therapy. Because of thei...

Time-lapse cinematographic analysis of beryllium--lung fibroblast interactions.

The proliferative response to beryllium chloride of cells in a population of human lung fibroblasts was quantitatively assessed using time-lapse cinematography. A dose of 0.02 microgram Be/ml, known to decrease the growth rate of fibroblasts, affects an estimated 75% of the cells in the population, increasing their interdivision time (IDT) by approximately 5 hr. The differences in mean 1n(IDT) between treated and control cells were essentially constant for comparable culture sizes ranging from 25 to 250 cells. There was no correlation between mother and daughter cell IDTs in control or treated culture at any culture size. IDTs of sister pairs were highly correlated in control cultures at selected culture sizes while sister pair IDTs of treated cultures were not. The data suggest that while beryllium alters the IDT of fibroblasts, an effect not related to culture size, any given cell affected by beryllium does not impart effects of the mineral to its progeny.

Effects of silica on human lung fibroblasts: Survival data analysis of time-lapse cinematography data☆

Abstract Silica, a fibrogenic material, enhances the proliferation of human lung fibroblasts. Analysis of filmed time-lapse sequences of dividing cells indicates that cell cycle time (or interdivision time, IDT) is significantly decreased in cells exposed in vitro to pure α-quartz. Migration rates for silica-treated cells were larger than those for control cells, but migration rate was not correlated with IDT. To analyze the IDT data, a computer program was used which carries out a nonparametric analysis of survival data (survival time being the IDT or cell cycle time of a given cell).

COMPUTER PROCESSING OF CELL LINEAGE DATA FROM TIME LAPSE CINEMATOGRAPHY STUDIES

Time lapse cinematography (TLC) affords a direct approach to the in vitro study of the growth of cell populations. A computer program is described that facilitates TLC studies by simplifying the transfer of data from the film review record to computer files, detecting recording and keypunching errors, calculation and printing statistical summaries, and graphical displays of the clone genealogy.

Mutation In Vivo in Human Somatic Cells: Studies Using Peripheral Blood Mononuclear Cells

We review here our efforts to develop a direct mutagenicity test system for detecting somatic cell mutations occurring in vivo in man. Our specific goal is to provide a useful test for directly quantifying mutant cells in human blood samples.

Direct Assay by Autoradiography for 6-Thioguanine-Resistant Lymphocytes in Human Peripheral Blood

There is great current interest in tests that may be useful for human mutagenicity monitoring. Mutagenicity monitoring, as contrasted with mutagenicity screening, is based on methods that detect evidence of genetic damage — whether germinal or somatic — that occurs in vivo. Most current short-term mutagenicity tests, however, have been developed for screening, i.e., for in vitro mutagenicity testing of chemicals or other agents with mutagenic potential.

Thioguanine Resistant Lymphocytes as Indicators of Somatic Cell Mutation in Man

This paper briefly reviews studies, which, over the past several years in our laboratory, have resulted in the development of a presumptive test for somatic cell mutation occurring in vivo in man. The test enumerates in vitro variant 6-thioguanine resistant (TGr) peripheral blood lymphocytes (PBL’s). Conditions of testing are such that variant-producing events (presumably mutations) antedate the assay and must occur in vivo. Tests of this kind are called direct mutagenicity tests (1) and have unique advantages for human mutagenicity monitoring.