A barostat was used to examine the effect of changes in posture on the volume and pressure in a bag positioned in the proximal stomach of 14 normal volunteers. Volumes in the supine position were compared with those in the standing, left lateral and right lateral positions at a constant pressure 2 mmHg above basal intragastric pressure. A separate series of measurements was then used to evaluate the effects of the same postural changes on pressure within the bag whilst its volume was kept constant. Changing from the supine to the left lateral position decreased bag volume by 62% when pressure was controlled; pressure increased by 60% when volume was controlled. In contrast, movement from the supine to the right lateral position resulted in a 68% increase in bag volume and a 31% fall in pressure. Moving from supine to standing had inconsistent effects on bag volume and pressure. There was a negative correlation between the magnitudes of the changes in pressure and volume (r2 = 0.557). The observed effects of posture probably result from changes in the compression of the stomach by abdominal viscera and indicate that subject position must be specified and maintained constant in studies of proximal gastric motor function using a barostat.
Aims In man a neurokinin-1 (NK 1 ) receptor antagonist has previously been shown to be ineffective in the prevention of motion-induced nausea. The antiemetic ef®cacy of NK 1 receptor antagonists against chemotherapy-induced emesis is, however, enhanced when combined with a 5-HT 3 receptor antagonist. Hence the ef®cacy of the NK 1 antagonist GR205171 in combination with the 5-HT 3 antagonist ondansetron (Zofran 2 ) was assessed in motion-induced nausea. Methods GR205171 25 mg i.v., with and without concomitant administration of ondansetron 8 mg i.v., and hyoscine hydrobromide 0.6 mg orally (positive control) were compared with placebo in a model of motion-induced nausea. The study was performed to a four-period, randomized, balanced, double-blind, crossover design in 16 healthy subjects. The end-point was the exposure to the motion stimulus required to produce moderate nausea in the subjects. Results The motion stimulus required to produce moderate nausea was signi®cantly greater for the positive control than placebo (P<0.001). There was no signi®cant difference between either GR205171 or GR205171 plus ondansetron and placebo (P=0.648 and 0.342, respectively). Conclusions The enhancement of NK 1 receptor antagonist antiemetic activity through combination with a 5-HT 3 receptor antagonist is not replicated in motion-induced nausea.
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