A competitive angiotensin converting enzyme antagonist SQ 20, 881 (SQ), was used to examine the role of the renin-angiotensin system in putative renin-dependent thirst in the albino rat. Significant enhancement of "renin-dependent" as well as renin-independent drinking was observed in the presence of peripheral SQ. Intraventricular SQ obviated this enhancement of drinking but did not affect the water intake caused by the original stimulus itself, whereas it sharply reduced drinking evoked by peripheral renin in nephrectomized rats. Prior renin depletion likewise had no influence on so-called renin-dependent thirst.

This study was undertaken to determine if a computerized pharmacokinetic program for adjusting theophylline infusion rates could attain a goal serum theophylline level more accurately than physician-derived adjustments and what clinical impact this would have. Thirty-five patients with diagnoses of asthma or chronic obstructive pulmonary disease were randomized to a control group (empiric) or experimental group (kinetic) after initial theophylline levels were drawn from each group. After second levels were drawn, patients in the kinetic group had their infusion rates adjusted by the computerized pharmacokinetic program to achieve a level of 15 mg/L, whereas patients in the empiric group had their infusions adjusted empirically by the primary care physicians to achieve a serum theophylline level of 15 mg/L. A final theophylline level was obtained just before the infusion was discontinued. The kinetic group was closer to the goal level of 15 mg/L than the empiric group, but this was not statistically significant (14.8 +/- 4.4 versus 12.6 +/- 4.1; p > 0.05). The total number of days that patients were receiving intravenous theophylline was slightly longer for the kinetic group (4.1 +/- 3.3 versus 3.2 +/- 1.5; p > 0.05) as was the total number of hospital days, but neither of these were statistically significant (11.4 +/- 21.6 versus 8.8 +/- 15.4 days; p > 0.05). There were no differences between the two groups in the number of subtherapeutic or toxic levels, and there were no significant differences in arterial blood gas measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Sixty-four patients with non-insulin-dependent diabetes mellitus were treated with a combination of insulin and oral sulfonylurea therapy in a double-blind, placebo-controlled trial during a 12-month period. Combination therapy lowered fasting glucose levels significantly only at the third and fourth months of treatment. Glycohemoglobin levels were significantly lower than control at 3 and 6 months whereas C-peptide levels were significantly increased at 3 and 9 months. Responders exhibited as much as a 50% reduction in total insulin dose compared with nonresponders or control subjects. These results suggest that combination therapy affords transient metabolic improvement in certain patients with non-insulin-dependent diabetes. Improvement in fasting glucose levels appears to be mediated by enhanced insulin secretion. Combination therapy may increase the cost of treatment by nearly 50% and appears warranted only in selected patients.

No abstract

CYP2D6 is one of the most polymorphic of the cytochrome P450 enzymes. Genetic differences in this enzyme have been reported in whites, blacks, and Asians. However, there is very little information about polymorphisms of this enzyme in Mexican Americans. The objectives of the present study were to assess the metabolic activity of CYP2D6 in a Mexican American population using dextromethorphan and to correlate this metabolic activity with a genotypic analysis. The sample consisted of 50 Mexican American subjects and 25 non-Mexican American controls. Overnight urine samples were collected and analyzed by high-performance liquid chromatography to calculate the metabolic ratio of dextromethorphan to dextrorphan. Blood samples were collected for genotypic analysis of CYP2D6 alleles. The frequency of the poor metabolizer phenotype was the same in the Mexican American group and the non-Mexican American group (6% vs 5.5%). The frequency of alleles in the Mexican American group was similar to frequencies published in other reports for non-Hispanic whites: *4 = 0.17, *5 = 0.02, *10 = 0.01, *17 = 0.02, *xN = 0.03. These results indicate that compared with non-Hispanic whites, Mexican Americans have a similar proportion of poor metabolizer phenotype and similar genetic polymorphisms of CYP2D6.