Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST Study.

BACKGROUND: Aromatase inhibitors (AIs) are accepted as adjuvant therapy for postmenopausal women (PMW) with hormone-responsive early breast cancer (EBC) with superior efficacy to tamoxifen. However, increased bone loss is associated with AIs. PATIENTS AND METHODS: PMW with EBC receiving letrozole (2.5 mg/day for 5 years) were randomly assigned to immediate zoledronic acid (ZOL; 4 mg every 6 months) or delayed ZOL (initiated only for fracture or high risk thereof). RESULTS: Patients (N = 1065) had a median age of 58 years; 54% had received prior adjuvant chemotherapy. At 36 months, mean change in L2-L4 bone mineral density (BMD) was +4.39% for immediate versus -4.9% for delayed ZOL (P < 0.0001). Between-group differences were 5.27% at 12 months, 7.94% at 24 months, and 9.29% at 36 months (P < 0.0001 for all). At 36 months, the immediate-ZOL group had a significant 41% relative risk reduction for disease-free survival (DFS) events (P = 0.0314). Adverse events are consistent with the known safety profiles of the study drugs. CONCLUSIONS: At 36 months, immediate ZOL was more effective in preserving BMD during letrozole therapy. Immediate versus delayed ZOL led to significantly improved DFS. Benefits are observed in the context of a favorable, well-established safety profile for letrozole and ZOL.

Effect of "renal-dose" dopamine on renal function following cardiac surgery.

The efficacy of renal-dose dopamine to improve renal function or reduce renal impairment was studied in 52 patients undergoing elective coronary artery bypass surgery. The patients were prospectively randomised in a double-blind fashion to receive dopamine at 200 micrograms/min (group D) or placebo (group P) from induction for 24 hours. Although dopamine improved haemodynamics, there was no effect on urine output at 4 hours (D = 917, P = 1231 ml: P = 0.066); urine output at 24 hours (D = 3659, P = 3304 ml: P = 0.36); creatinine clearance at 0-4 hours (D = 104, P = 127 ml/min: P = 0.27); creatinine clearance on admission to ICU-4 hours (D = 94.8, P = 83.4 ml/min: P = 0.48); creatinine clearance at 20-24 hours (D = 91.2, P = 107 ml/min: P = 0.48); free-water clearance at 0-4 hours (D = 29.6, P = -59.8 ml/hr: P = 0.069); free-water clearance at 20-24 hours (D = 43.2, P = -48.9 ml/hr: P = 0.55). The incidence of transient renal impairment was similar in both groups (D = 36%, P = 50%: P = 0.65). Our study failed to demonstrate that routine prophylactic renal-dose dopamine is associated with improvement in renal function, or with prevention of transient renal impairment in patients undergoing coronary artery bypass surgery.

Piracetam in elderly motorists.

101 elderly motorists with reduced reaction capacity were examined under real traffic conditions with regard to their driving ability. They were given a daily dose of 4.8 g piracetam or placebo over a six-week period in a randomised double-blind study. The percentage of correctly solved sign-observance items, which reflects orientation and perception in real traffic conditions, increased in the placebo-treated test-group from 79.86% in the pretest to 80.07% in the retest, whereas the test subjects of the piracetam-treated group improved their performance from 77.08% to 84.16%. After being treated with piracetam for 6 weeks, the drivers showed a significantly better performance than the placebo-group. Of particular interest is the finding that the test-subjects who had scored less than 80% in the pretest improved without exception in the retest after treatment with piracetam.

Avoidance of precipitation and carbohydrate breakdown in autoclaved plant tissue culture media.

The extent of breakdown of fructose and glucose derived from sucrose in the medium of Murashige and Skoog (1962) during autoclaving was investigated by polarographic measurement. Although not present in the original MS medium but often used in place of FeSO4 + Na2-EDTA, FeNa-EDTA was found to be primarily responsible for catalyzing the breakdown of these monosaccharides. It would therefore be good practice to autoclave FeNa-EDTA separate from the carbohydrate constituents of the medium in order to reduce the formation of toxic substances derived from the latter's breakdown. Autoclaving FeNa-EDTA separately has the additional advantage of preventing precipitation of certain micronutrient elements. Further precipitation can be avoided by autoclaving FeNa-EDTA and KH2PO4 together, but separately, from other components of the medium. By eliminating precipitation and minimizing the breakdown of monosaccharides during autoclaving, it is possible to improve the quality of the medium without resorting to sterilization by filtering.