Circadian rhythm modulated 5-FUdR infusion with Megace in the treatment of advanced pancreatic cancer.

Thirteen patients with advanced pancreatic carcinoma were treated with circadian rhythm modulated infusion of 5-FUdR and Megace. Treatment was initiated at a dose of 0.15 mg/kg/day for 14 days every 28 days and was increased or decreased by 0.025 mg/kg/day with each subsequent cycle until maximum tolerated dose (MTD) was achieved. Megace (200 mg) was administered daily in divided doses. One-third of the patients were able to complete > or = 6 cycles of treatment, one-half could only complete < or = 2 cycles, and the remainder managed 3-4 cycles. No patients had regression of disease, but a small number, who were able to receive 6-7 months of treatment, achieved stable disease in the short term. In conclusion, treatment was fairly well tolerated. However, increased dose intensity by this method did not significantly increase response rate. In only a few patients was disease stabilized for a brief period. Megace did not materially improve nutritional status. CA-19-9 levels did not correlate well with disease activity.

A psychophysical measure of visual and kinaesthetic spatial discriminative abilities of adults and children.

Quantitative estimates of the spatial discriminative capacities of the visual and kinaesthetic systems in adults and children were obtained. Intersensory integration was investigated by including spatial discriminations based on congruent visual plus kinaesthetic reafference. The psychophysical method of adjustment was used with simultaneous comparisons of a fixed and a variable stimulus. The subject's task was to estimate when the variable stimulus (ellipse) was identical to the standard one (circle), under one of three modality conditions: vision, kinaesthesis, and vision plus kinaesthesis. After a pilot study with adults, children (aged 8, 10, and 12 years) and adults were both tested. Subjects from each age group were randomly allocated to each of the three experimental conditions. Results show that the visual and kinaesthetic estimates of the 8- and 10-year-old subjects did not differ significantly, but the visual responses of the adults and 12 year olds were significantly more accurate than corresponding kinaesthetic estimates. Bisensory estimates were significantly more accurate than visual responses only for the 8- and 10-year-old age groups. Intramodal comparisons showed the kinaesthetic estimates of the 8, 10, and 12 year olds to be significantly more accurate than the corresponding adult performance. Adult visual estimates were significantly more accurate than those made by 8 year olds, but were not significantly different from the visual responses of 10 and 12 year olds. Estimates based on bisensory reafference did not differ from each other across the four age groups. It is concluded that modality adeptness and dominance are task dependent and empirically determined rather than being innate properties of sensory systems. The data indicate that intersensory differentiation rather than integration occurs with maturity.

Disruption of passive avoidance learning in the rat by electrical stimulation of the hippocampus.

The effect of electrical stimulation to discrete regions of the dorsal hippocampus on passive avoidance was examined in five experiments. Rats stepped from a brightly lit, white compartment to a dark compartment. Following footshock in the dark compartment, step-through latencies were recorded 1 min, 24 hr, and 48 hr after footshock. When given 20 step-through trials prior to footshock, dentate-stimulated animals exhibited lack of passive avoidance with particularly short latencies at 1 min, and CA1 rats showed reduced latencies compared with latencies of cortical and nonoperated controls. In Experiment 2, rats given stimulation in the same regions performed the avoidance task without prior step-through experience. All groups showed less passive avoidance than the control group in Experiment 1, and there were no significant differences between groups. With a single step-through trial before the footshock trial, longer avoidance latencies were recorded, but again groups did not differ significantly. Dentate-implanted animals, given 20 prior exposure trials but with stimulation at different stages of the task sequence, demonstrated a passive avoidance deficit at 1 min after footshock. The results are discussed in terms of the generation of expectancy that the black compartment was a safe place and the effects of brain stimulation on the expectancy, with particular reference to Vinogradova's (1975) theory of hippocampal function.