Treatment of lower urinary tract infections with single-dose trimethoprim-sulfamethoxazole.

Two hundred three women from a primary care medical practice with symptoms of lower urinary tract infection and positive urine cultures were treated with trimethoprim-sulfamethoxazole. One hundred eleven women received a single dose and 92 were treated for ten days. Cure rates were 87 percent and 89 percent, respectively, one week after therapy. A narrow 95 percent confidence interval for the difference between the two cure rates (.02 +/- .09) suggests the treatments are equally effective. Patients were followed by chart audit and a self-reporting questionnaire. No difference in recurrence rates was found between the two groups six months after therapy. Single-dose trimethoprim-sulfamethoxazole is as effective as ten-day treatment in women with symptoms suggestive of lower urinary tract infection and has no greater relapse rate.

Reduced mutant yield at high doses in the Salmonella/activation assay: the cause is not always toxicity.

In the Salmonella/activation assay developed by Ames et al [1973, 1975] toxicity is not measured, though it is recognized by the loss of a cloudy appearance on the plate. One approach to the measurement of toxicity is described here and uses a microscope-linked automated colony counter to estimate the number of microcolonies formed by histidine auxotrophs that stop growing after the depletion of histidine. This technique was used to evaluate the effect of toxicity on the revertant count for 16 mutagens, most of which were chosen because, from previous experience, their dose-response curves manifested a maximum at an intermediate dose tested. One of the sixteen, 2-nitrofluorene, was not toxic up to the maximum dose tested. The relationship between mutation and toxicity for the remaining fifteen allowed them to be grouped into two categories: (1) compounds that induced decreases in survival at the same dose at which the number of mutants decreased, and (2) compounds that induced toxicity, but survival was reduced at dose levels higher than those required to reduce the number of mutants. Possible explanations for this reduction of mutant counts occurring with little apparent concomitant increase in toxicity are examined. These results may be significant for attempts to estimate mutagenic potency and, to a lesser extent, construct mathematical models of the Ames test.

Differing activation pathways for 2-acetylaminofluorene to a mutagen in vitro.

The mutagenicity of 2-acetylaminofluorene (AAF) in S. typhimurium TA 1538 was investigated using Ames' test and activation systems based upon rat- or cotton rat-liver post-mitochondrial supernatant (S9) fractions. Part of this study involved sub-fractionation of S9 into microsomes (M) and 100,000 X g supernatant (S100) fractions. With a rat liver-derived fractions, mos activity was associated with S100; M-activating potential was never greater than that achieved with S9. In cotton rats, most activating potential was associated with S9. This activity was greater than could be accounted for by the separated cotton-rat M and S100 components. Reconstituted, cross-species 'S9' fraction studies showed that the dominant determinant of S9 properties was the M fraction in both rats and cotton rats. The principal co-factor required in the activation reactions was NADPH, but it could be largely replaced by NADH. 7,8-Benzoflavone inhibited activation both in M and S100 whereas paraoxon had no effect upon rat S100 activation, but had a marked effect upon cotton-rat M activation.