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Background. The short elimination half-life of metoclopramide necessitates frequent administration for optimal relief of nausea. This study compares a newly developed controlled release preparation of metoclopramide (CRM) and immediate release metoclopramide (IRM) with respect to efficacy, safety, and pharmacokinetics in patients with chronic nausea associated with advanced cancer. Methods. Thirty-four patients with advanced cancer with nausea lasting more than 1 month and with no evidence of involvement of the gastrointestinal tract, peptic ulcer or gastritis, brain metastases, or metabolic abnormalities were randomized, in a double-blind cross-over study, to receive 40 mg of CRM every 12 hours or 20 mg of IRM every 6 hours for 3 days. Nausea, food intake, and side effects were assessed four times daily. On Day 3, sequential venous samples were taken (12 patients) to determine plasma metoclopramide concentrations. Results. In 29 evaluable patients, the intensity of nausea on Day 3, measured by a 0-100-mm visual analogue scale and 0-3 categoric scale was 15 [+ or -] 17 and 0.6 [+ or -] 0.6 after IRM, versus 8 [+ or -] 9 (P = 0.033) and 0.4 [+ or -] 0.5 (P = 0.055) after CRM, respectively. Visual analogue scale nausea scores recorded by time of day and by day for the 3 treatment days were significantly lower for patients who received CRM compared with those who received IRM (P = 0.047 and P = 0.043, respectively), but categoric nausea scores were not significantly different between treatments by time of day and by day across the 3 treatment days. No differences were observed in caloric intake or side effects between treatments. In a pharmacokinetic analysis, the CRM/IRM ratio for area under the [curve.sub.0-12] ([mu]g x hours x [L.sup.-1]), [C.sub.max] ([mu]g/L), and [T.sub.max] (hours) was 100%, 98%, and 2.3 fold, respectively. Conclusion. Controlled release metoclopramide is safe and effective in managing chronic nausea in patients with advanced cancer. Future studies should focus on characterizing this syndrome more clearly and on determining the optimal dose of metoclopramide and the effects of drug combinations that have proven to be useful in managing chemotherapy-induced emesis (i.e., metoclopramide plus corticosteroids).

Background. The short elimination half-life of hydromorphone necessitates 4-hourly dosing to maintain optimal levels of analgesia in patients with chronic cancer pain. The purpose of this study was to compare the clinical efficacy and safety of controlled release hydromorphone administered every 12 hours and immediate release hydromorphone administered every 4 hours in patients with chronic severe cancer pain. Methods. Forty-eight patients with stable chronic severe cancer pain were randomized, in a double-masked crossover study, to controlled release hydromorphone every 12 hours or immediate release hydromorphone every 4 hours for 7 days each. Pain intensity was assessed using a visual analog scale (VAS) and the Present Pain Intensity Index of the McGill Pain Questionnaire. Nausea and sedation were also assessed using a VAS. Assessments were made by the patient four times a day at 7:00 a.m., 11:00 a.m., 3:00 p.m., and 7:00 p.m. Use of rescue hydromorphone also was recorded by the patient. Results. Forty-five patients completed the study (26 women, 19 men; mean age, 57.1 [+ or -] 13.6 years) and received a mean daily dose of 76 [+ or -] 133 mg (range, 6-768 mg). There were no significant differences between controlled release hydromorphone and immediate release hydromorphone in overall VAS pain intensity scores (19 [+ or -] 14 vs. 20 [+ or -] 14 mm), ordinal pain intensity scores (1.2 [+ or -] 0.8 vs. 1.2 0.8) and pain scores by day of treatment or time of day. The daily rescue analgesic consumption during controlled release hydromorphone and immediate release hydromorphone did not differ significantly overall (1.1 [+ or -] 1.1 vs. 1.0 [+ or -] 1.1 doses per day) or with respect to time of day. There were no significant differences in overall VAS sedation scores (18 [+ or -] 18 mm vs. 19 [+ or -] 18 mm) and in overall mean VAS nausea scores (12 [+ or -] 15 mm vs. 11 [+ or -] 14 mm) between controlled release hydromorphone and immediate release hydromorphone. Conclusion. Controlled release hydromorphone administered every 12 hours is as effective as immediate release hydromorphone administered every 4 hours in the management of patients with chronic severe cancer pain. The benefits of controlled release hydromorphone lie in the convenience of its capsule formulation, which can be sprinkled on soft food, and its 12-hour duration of action, which allows patients uninterrupted sleep and improved compliance. Cancer 1994; 74:1808-16.

The JET Trace Tritium (TTE) programme marked the first use of tritium in experiments under the managerial control of UKAEA, which operates the JET Facility on behalf of EFDA. The introduction of tritium into the plasma by gas fuelling and neutral beam injection, even in trace quantities, required the mobilisation of gram-quantities of tritium gas from the Active Gas Handling System (AGHS) product storage units into the supply lines connected to the torus gas valve and the neutral beam injectors. All systems for DT gas handling, recovery and reprocessing were therefore recommissioned and operating procedures re-established, involving extensive operations staff training. The validation of Key Safety Related Equipment (KSRE) is described with reference to specific examples. The differences between requirements for TTE and full DT operations are shown to be relatively small. The scientific motivation for TTE, such as the possibility to obtain high-quality measurements in key areas such as fuel-ion transport and fast ion dynamics, is described, and the re-establishment and development of JET’s 14MeV neutron diagnostic capability for TTE and future DT campaigns are outlined. Some scientific highlights from the TTE campaign are presented.

SUMMARYObjective: Toconduct a preliminary evaluation of a new oral formulation of controlled-release (CR) oxybutynin tablet taken once-daily in patients with urinary urge incontinence.Research design and methods: A single-centre, open-label, 8-week study was conducted. Patients with urodynamically-confirmed detrusor instability, micturition frequency (> 8 voids/day) and/or urinary incontinence (> 2 incontinence periods/day) were enrolled. The study duration was 8 weeks: patients received IR oxybutynin (2.5-5 mg bid) for 2 weeks, followed by a 2-week washout/baseline period to avoid carryover effects, and oral CR oxybutynin (15 mg OD) for 4 weeks. Daily void frequency, fluid intake, urinary incontinence episodes, and spontaneously reported adverse events were recorded in a daily diary for five consecutive days in each treatment period.Results: Of 12 enrolled patients, 9 patients completed the study and were evaluable for efficacy; all patients were evaluable for safety. Compared to baseline/washout, CR oxybutynin reduced UI episodes/day by 45 (p  0.13) and micturitions/day by 15 (p  0.07). Treatment with IR oxybutynin (mean dose: 6.7 ± 2.5mg/day) reduced UI episodes/day from baseline by 7 (p  0.58) and voids/day by 6 (p  0.29). Fluid intake remained consistent at approximately 2 litres/day during all study periods. The most common adverse event was dry mouth.Conclusion: Based on the reductions in daily frequency of incontinence and micturition following 4-weeks treatment, CR oxybutynin (15 mg OD) was at least as effective as the patients' previous dose of IR oxybutynin (mean dose: 6.7 ± 2.5 mg/day). These improvements were achieved without restriction of fluid intake. Initial 15mg doses of CR oxybutynin appear to be well tolerated.

In an open safety-in-use study, the subjective effectiveness and taste acceptability of a new high-potency antacid product were compared to previous treatment in 109 patients presenting with upper gastro-intestinal disorders of functional origin. Severity of the dominant symptoms prior to treatment was compared with that of symptoms present during treatment. Sixty-seven per cent to 73% of upper gastro-intestinal tract symptoms were completely relieved. Eighty-three per cent versus 48% of patients seen in a private practice setting, as compared with the speciality practice, reported good to excellent results, with 92% versus 56% describing good to excellent taste acceptability. When compared with previous antacid therapy, 70% of the patients preferred the new high-potency formulation to the regular-strength products, for both effectiveness and taste. The incidence of product-related side effects was low, with only 6·7% experiencing the diarrhoea or loose stools commonly associated with conventional products containing magnesium hydroxide.

ABSTRACT: In a four‐week study, a comparison was made of oxazepam, flurazepam and chloral hydrate as hypnotic sedatives in 17 geriatric patients. Each drug was given alone for six nights, with a two‐night placebo interval following each phase. Each patient completed an additional placebo phase (up to six nights) before each drug phase. The number of awakenings per night and the sleep latency (time required to fall asleep) were determined from the patients' reports and from the reports of a nurse‐observer. Only for oxazepam was the number of patient‐reported awakenings per night significantly less than for placebo, although with both oxazepam and flurazepam the awakenings were fewer than with chloral hydrate. According to the patient‐reports, sleep latency was significantly lower with flurazepam than with placebo; for oxazepam and chloral hydrate the latencies were not significantly different from those for flurazepam or placebo. Only for oxazepam were the patients' ratings of sleep quality significantly greater than for placebo. The objective assessment of sleep by the nurse‐observer usually confirmed the patients' assessments. Morning drowsiness was the most common side effect, reported equally for placebo and for the active drugs. Drowsiness during the day was reported less frequently for oxazepam than for flurazepam, chloral hydrate or placebo. It is concluded that oxazepam is safe and efficacious for the short‐term management of insomnia in the elderly.

1. Pressure in the duct of the submaxillary gland of the cat was recorded under chloralose anaesthesia. Single pulses applied to the parasympathetic nerve caused a pressure rise.

1. Submaxillary gland blood flow and salivation have been measured in anaesthetized cats and the chorda‐lingual nerve has been stimulated at different frequencies.