Flunarizine in stroke treatment (FIST): a double-blind, placebo-controlled trial in Scandinavia and the Netherlands.

INTRODUCTION: An international, multicenter trial was conducted in 331 patients to determine the effect of a large dose of flunarizine (a calcium entry blocker) in the treatment of acute ischemic stroke in the territory of the Middle cerebral artery. METHODS: The administration of the trial medication should start within 24 h after the initial symptoms of stroke. According to a random schedule, the patients were assigned to a 4-weeks double-blind treatment with either flunarizine (n = 166) or placebo (n = 165): one week intravenous administration (50 mg daily), followed by 3 weeks oral treatment (week 2, 21 mg daily; week 3-4, 7 mg daily). All patients had to be investigated by computerized tomography (CT) within 7 days after stroke onset; 36 patients were secundarily excluded because the CT showed another pathology. During the treatment period, other "stroke therapies" were not allowed. Patients were followed up for 24 weeks. RESULTS: After the 24 weeks trial period, the percentage of patients who were dead or pendent (modified Rankin score 3-5) was similar in both treatment groups (flunarizine 67%, placebo 65%). During the trial, the scores for handicap severity (modified Rankin scale), neurological status (Orgogozo) and activities of daily living (modified Barthel index) strongly improved in both treatment groups, but no differences were found between the treatment groups. In this trial, the administration of trial treatment started relatively late after stroke onset (flunarizine group: mean time interval 13.5 h; placebo 12.3 h). A subgroup of patients received trial medication within 6 h after stroke onset (flunarizine n = 31; placebo n = 29). Also in this subgroup, no differences were found between the flunarizine and placebo group. CONCLUSION: Flunarizine did not improve neurologic and functional outcome in patients with acute ischemic stroke.

Changes in blood manganese levels during pregnancy in iron supplemented and non supplemented women.

Blood manganese levels and iron status indices were determined each trimester in 66 healthy pregnant women. Twenty-five were randomly assigned to iron supplementation, 19 to placebo and 22 received dietary advise aimed at increasing their dietary intake of fibre. Iron supplemented women had significantly higher levels of blood haemoglobin compared to the levels of the two other groups, and higher serum ferritin levels compared to the placebo group. No significant difference in blood manganese levels was observed among the three groups of women. There was a significant increase in blood manganese levels from one trimester to the next, which was slightly more pronounced in non supplemented women. The median values in the three trimesters were 154 (range 79-360) nmol/L, 190 (range 98-408) nmol/L, and 230 (range 133-481) nmol/L, respectively. Pregnancy seems to change manganese status or otherwise influence manganese metabolism irrespective of iron status and iron supplementation.