Human gastric acid secretion following repeated doses of AG-1749

The effect of increasing doses (15 mg, 30 mg and 60 mg) of the substituted benzimidazole, AG-1749, on gastric acid secretion and fasting serum gastrin concentration has been studied after repeated administration to healthy volunteers. AG-1749 produced a dose-dependent and profound decrease in basal and stimulated gastric acid secretion in all volunteers, with almost total suppression at the highest dose. The extent of inhibition increased between Day 2 and Day 8 with the 15 and 30 mg doses of AG-1749. The inhibitory effect of AG-1749 appears to be fully reversible as control levels of acid output were reached 7 days after drug withdrawal. Seven days' dosing with 60 mg AG-1749 induced a more than threefold increment of fasting serum gastrin concentration, but this increase was still within the normal range. Seven days after cessation of dosing, fasting serum gastrin concentration returned to a pre-dose level.     

Recanalization of Chronically Occluded Coronary Arteries: Single-Center Experience in 400 Cases, Including Long-Term Angiographic Follow-Up

The study presented comprises the initial and angiographic long-term results of a consecutive series of recanaliza-tion procedures in a single center. Between 1988 and 1992, a total of 400 patients underwent transluminal recanalization for total coronary occlusions. In 82% of successfully attempted patients, the occlusion could be passed by a standard guidewire. The overall initial success rate was 75% (298 of 400). The highest success rates could be achieved in the left circumflex artery (84%) and left anterior descending coronary artery (77%). Complications were uncomplicated myocardial infarction in ten patients (2.5%) and death in two patients (0.5%). Angiographic follow-up 3–6 months after recanalization could be achieved in 263 (88%) of 298 patients. Significant restenosis (≥ 50% minimum lumen diameter) was found in 57 (22%) of 263, and reocclusion was present in 38 (14%) of 263 patients, resulting in a total recurrence rate of 36%. In conclusion, recanalization can be performed with an initial success rate of 75% using bare-wire technique under the prerequisite operator experience. If a nearly complete angiographic follow-up is performed, the overall recurrence rate is 36%, which seems to be very acceptable in comparison with PTC A results for incomplete obstructions published so far . (J Interven Cardiol 1996;9:73–79)     

FLUMAZENIL IN ALCOHOL WITHDRAWAL: A DOUBLE-BLIND PLACEBO-CONTROLLED STUDY

The purpose of the present study was to study -aminobutyricacid (GABA)-A receptor function in alcohol-dependent subjectsduring withdrawal, using the benzodiazepine antagonist flumazenil.In particular, we wanted to examine the hypotheses that an endogenousinverse agonist ligand at the GABA-A benzodiazepine receptor(GBzR) is active during withdrawal (in which case flumazenilshould be anxiolytic), or whether chronic alcohol intake resultsin a shift in sensitivity of the receptor in the inverse agonistdirection (in which case flumazenil should be anxiogenic). Resultsfrom 15 alcohol-dependent subjects in a double-blind placebo-controlledcross-over study showed that flumazenil was neither anxiolyticnor anxiogenic, although withdrawal scores were reduced duringthe course of the study. The fact that flumazenil was not anxiogenic,as it is in panic disorder, suggests that the GBzR is functioningdifferently in these two clinically similar conditions.