Gamma-aminobutyric acid: selective inhibition of electrically induced head-turning following intracaudate administration

GABA selectively antagonized head-turning elicited by electrical stimulation of the caudate nucleus in the rat when applied directly to the site of stimulation utilizing an electrode-cannula. Pretreatment with picrotoxin, a GABA antagonist, prevented the action of GABA on the head-turn response. This report provides in vivo evidence that GABA may play an inhibitory role in basal ganglia function. The findings are relevant to basal ganglia disorders in man.     

Rigid urethane foams from hydroxymethylated castor oil,safflower oil,oleic safflower oil,and polyol esters of castor acids

Castor, safflower, and oleic safflower oil derivatives with enhanced reactivity and hydroxyl group content were prepared by hydroformylation with a rhodium-triphenylphosphine catalyst, followed by hydrogenation. Rigid urethane foams prepared from these hydroxymethylated derivatives had excellent compressive strengths, closed cell contents, and dimensional stability. Best properties were obtained from hydroxymethylated polyol esters of castor acids.     

Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel

PURPOSE: Topotecan, a topoisomerase I inhibitor, was evaluated in a multicenter, phase II study of women with epithelial ovarian carcinoma who relapsed after one or two prior regimens that included platinum and paclitaxel. PATIENTS AND METHODS: Topotecan 1.5 mg/m2 daily was administered as a 30-minute infusion for 5 consecutive days on a 21-day cycle. Eligibility criteria included bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of 2 or less, and adequate bone marrow, liver, and renal function. Efficacy was assessed by independent radiologic review. RESULTS: One hundred thirty-nine patients were treated; 81% were platinum resistant. Sixty-two patients had received one prior regimen and 77 patients had received two prior regimens. Nine patients were not assessable for response; however, all patients were included in the response analysis. The overall response rate was 13.7%; 12.4% in platinum-resistant and 19.2% in platinum-sensitive patients. Stable disease lasted at least 8 weeks in 27.3% of the patients. The median duration of response and time to progression were 18.1 and 12.1 weeks, respectively. The median survival was 47.0 weeks. Grade 4 neutropenia occurred in 82% of the patients (34% of the courses) and thrombocytopenia in 30% of the patients (9% of the courses). Infectious complications occurred in 6% of the courses. Nonhematologic toxicities were mild. There were no drug-related toxic deaths. CONCLUSION: As a single agent, topotecan has modest activity in women with advanced epithelial ovarian carcinoma who have progressed or not responded after one or two prior regimens with platinum and paclitaxel. Further investigation of combination regimens is indicated in the primary therapy for ovarian cancer based on the mechanism of action and tolerability.     

A technique for the laboratory evaluation of the speed of onset of I.V. anaesthesia

A method is described for the evaluation of the speed of onset of i.v. anaesthesia in mice. The technique involves (a) determination of the median hypnotic dose (HD50) by plotting the probit value of the percentage of mice sleeping, against dose on a logarithmic scale, (b) plotting mean induction time over a range of doses against the logarithm of the dose and (c) comparison of induction times at 1.25 HD50. All doses were given over 1 s or 10 s. A 1-s injection was thought to be of most value in the evaluation of structure activity effects whereas the 10-s injection produced results similar to those which have been reported in man. With this technique, and using 1-s injection times, induction times were found to be similar with thiopentone and Althesin. Those following methohexitone, etomidate and propanidid were marginally longer whereas ketamine and pentobarbitone were obviously slower in onset.