A randomized controlled trial of oral selegiline plus nicotine skin patch compared with placebo plus nicotine skin patch for smoking cessation.

OBJECTIVES: To compare the effect of oral selegiline plus nicotine patch with placebo plus nicotine patch on smoking cessation rates. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Three community-based clinics. PARTICIPANTS: One hundred and nine male and female smokers aged 18-55 years, who smoked at least 15 cigarettes/day. INTERVENTIONS: Oral selegiline, 2.5 mg, or placebo twice/day initiated 1 week before the quit day, followed by 5 mg oral selegiline or placebo twice daily for 26 weeks, plus active nicotine skin patch to all participants for the first 8 weeks only. Measures of continuous abstinence rates up to 52 weeks, withdrawal symptoms, blood pressure and adverse events incidence. FINDINGS: Twenty-five per cent (14 of 56) were continuously abstinent for 52 weeks in the selegiline plus nicotine group compared with 11% (6 of 53) in the placebo plus nicotine group (P = 0.08). Craving for cigarettes was lower in the selegiline plus nicotine group 4 weeks after quit day (P = 0.02). CONCLUSIONS: Adding selegiline to nicotine patch was associated with a doubling of the 52-week continuous abstinence rate, but this difference was not statistically significant. Selegiline significantly reduced craving for cigarettes and appeared to mitigate the need for nicotine replacement therapy. The results suggest that selegiline is a promising drug for future smoking cessation research.

Preventing drug interactions by online prescription screening in community pharmacies and medical practices.

BACKGROUND: Drug interactions have been shown to be preventable by computerized prescription entry and screening only in hospitals and not in community-based practice. METHODS: We retrospectively evaluated the effect of online prescription screening in community pharmacies and physician offices of one health maintenance organization, phased in during 3 consecutive 6-month periods in 1998 to 1999 (period I, system active only in 40% of pharmacies; period II, system active in 90% of pharmacies and 50% of physician offices; period III, system active in 95% of pharmacies and 90% of physician practices), on rates of prescriptions with-, patient exposure to-, and physician prescribing of-potential drug interactions. FINDINGS: Cumulative data included 775,186 patients given at least one prescription, by one or more of 5504 physicians, whose prescriptions were dispensed at 572 pharmacies. Dispensing of drug interaction prescriptions was reduced by 21.1% and by 67.5% in periods II and III compared with period I (odds ratio, 0.79; 95% confidence limit, 0.75-0.83 and odds ratio, 0.28; 95% confidence limit, 0.26-0.30, respectively). Patient exposure decreased only in those receiving 3 to 7 concurrent drugs (odds ratio, 0.80; 95% confidence limit, 0.71-0.90) with no reductions for patients who were given 2 drugs or 8 or more drugs. Only 19% to 25% of physicians wrote prescriptions for drugs that interact, but 85% of these repeated this pattern after being alerted. The proportion of prescriptions of drugs that interact that originated with a single prescriber, as opposed to 2 prescribers, decreased during the 3 periods from 0.81 to 0.74 and 0.69 (P <.001). INTERPRETATION: Computerized prescription entry and drug interaction screening in the community caused a 62.8% reduction in pharmacy-dispensed prescriptions with severe drug interactions and a 20% reduction in patient exposure to prescriptions with severe drug interactions; this reduction was negated by polypharmacy of 8 or more drugs. The effect of interaction alerts on physician prescribing patterns was limited.

Diabetes and ischemic heart disease among Yemenite immigrants in Israel.

BACKGROUND: The pattern of diabetes and ischemic heart disease among emigrants from pre-industrialized societies to more developed countries may be explained by both genetic and environmental factors. OBJECTIVES: To describe and interpret the pattern of diabetes and ischemic heart disease among Yemenite immigrants in Israel and their second-generation offspring. METHODS: Medical record charts of adult Yemenites were surveyed in a primary care health center, and the data were compared with prevalence rates derived from a non-Yemenite population. RESULTS: There was a marked excess of non-insulin dependent diabetes mellitus among Yemenite immigrants over 45 years of age, but not of hypertension or ischemic heart disease. Yemenites with diabetes were far less likely to develop ischemic heart disease than non-Yemenites with diabetes (odds ratio for non-Yemenites compared with Yemenites, 3.5; confidence interval 1.54 < OR < 7.77). CONCLUSIONS: There was less of an association between diabetes and ischemic heart disease among Yemenites. This finding requires further investigation of the relative roles of genetic and environmental factors.

Enhancement of 5-fluorouracil anabolism by methotrexate and trimetrexate in two rat solid tumor models, Walker 256 carcinosarcoma and Novikoff hepatoma, as evaluated by 19F-magnetic resonance spectroscopy.

Although 5-fluorouracil (5-FU) is one of the most effective single agents in treating solid tumors, its low effectiveness as a single agent has led to development of a number of modulators intended to enhance its therapeutic effectiveness. Of these, methotrexate (MTX) and trimetrexate (TMTX) have been shown to have synergistic anticancer activity with 5-FU. The effect of these two drugs on the uptake and the intratumoral metabolism of 5-FU was studied in two rat tumor models using 19F-nuclear magnetic resonance spectroscopy: on excised samples of Walker 256 carcinosarcoma and noninvasively (in vivo) in Novikoff hepatoma. In the rats bearing the Walker 256 tumor, a 4-hr pretreatment with MTX showed the maximal increase in the rate of conversion from 5-FU to its fluorinated nucleotides/nucleosides. In the rats bearing the Novikoff hepatoma, both modulators increased the amounts of cyctotoxic anabolites of 5-FU, but at the doses administered, the cumulative amounts of 5-FU anabolites formed after MTX were significantly higher than those formed after TMTX or after saline control. On the other hand, the increase in the levels of the fluorinated nucleotides/nucleosides after TMTX peaked at a later time. The possible significance of these findings is that timing of administration of a modulator is important because it affects both transport and metabolism of 5-FU. The two modulators studied, both antifolates, act differently on transport and on metabolism: MTX affects both, whereas TMTX, at the level studied, appears to affect predominantly the metabolic process. In addition, significant differences exist between tumor models. These data suggest possible mechanisms and processes that should be studied further in humans, using these noninvasive pharmacokinetic imaging methods for monitoring 5-FU targeting and metabolism.

Dynamics of yield components and essential oil production in a commercial hybrid sage (Salvia officinalis x Salvia fruticosa cv. Newe Ya'ar no. 4).

The fresh yields, the essential oil content, and the quality of a sage hybrid (Salvia officinalis x Salvia fruticosa, cv. Newe Ya'ar No. 4, Lamiaceae) as affected by development and harvest time were determined. Marked increases in plant height and in the number of nodes developed per plant together with a modest increase in leaf size were accompanied by dramatic increases (more than 20-fold) in the fresh yields throughout a 50-day growth period. No major changes in the essential oil content per fresh weight and its composition were detected throughout the growth period. In contrast, the compositions of the essential oils obtained from stems, as compared to leaves and leaf-primordia, had marked differences. Developmentally controlled changes in the extractives from individual leaf pairs from the same plant were also noted. In upper young leaves, the oxygenated diterpene manool and the sesquiterpene hydrocarbons alpha-humulene and beta-caryophyllene constituted up to 20%, 8%, and 4% of the total extractives, respectively. In older leaves, the abundance of these components steadily dropped to roughly half their levels in young leaves. Conversely, the proportions of the monoterpenes, particularly the ketones camphor and alpha-thujone, steadily increased with leaf position. Minor changes in the levels of other extractives were also recorded. These studies imply independent regulatory patterns for di-, sesqui-, and monoterpenes in this sage hybrid, and suggest possible agrotechnical means to obtain preferred chemical compositions of its essential oil.