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The partial transmission zone (PTZ) measured in air and its radiation shadow components are identified quantitatively and qualitatively for both cuboid and beam-divergence-shaped blocks. Source-block distance (SBD) and source-surface distance (SSD) are varied to produce SBD/SSD ratios from 0.71 to 0.86. The variation of the magnitude of the radiation shadow components as a function of SBD/SSD is explained in terms of a radiation shadow model. The clinical significance of PTZ minimization and a comparison between PTZs of 'shaped' and 'nonshaped' blocks is discussed. For small ratios of SBD/SSD the beam-divergence-shaped blocks produce smaller medial and lateral PTZs, whereas for larger ratios in the order of 0.9 the medial PTZ is also small for the cuboid blocks. Both PTZs, in general, decrease with increasing SBD/SSD ratios and for both cuboid and beam-divergence-shaped blocks.

The possible role of dynorphin, an endogenous opioid peptide, in the regulation of appetite was studied in male genetically-obese (Zucker) rats and their litter mates of normal weight. Eighteen pairs were divided into 3 treatment groups: control, acutely dynorphin-treated (5 mg/rat), and implanted with Alzet mini-osmotic pumps containing 2 mg dynorphin to be delivered at a rate of 10 micrograms/hr. Body weights and food and water consumption were determined daily for 7 days. Body weights were not significantly changed from initial values for any treatment group. Food and water consumption per 24 hours were generally the same for obese rats and their normal littermates, but in terms of consumption per 100 g body weight, the obese rats generally consumed less food and water. Neither acute nor continuous dynorphin administration affected consummatory levels.

Male ICR mice, young (25-days old), mature (3-months old), and old (22 months), were injected with morphine sulfate (10 mg/kg, s.c.) or were implanted with morphine pellets (75 mg). Controls received saline injections or placebo pellets. One hour after injections and 72 h after pellet implantations, the mice were decapitated and striatal regions were removed for the following analyses: calmodulin (CaM) levels via radioimmunoassay and activities of cyclic nucleotide phosphodiesterases, adenylate and guanylate cyclases, and Ca2+, Mg2+-ATPase. Acute morphine treatment produced the following: (1) increases in calmodulin levels in the young and old mice while having no effect on mature levels; (2) increases in activities of guanylate cyclase of mature mice while decreasing those of the old mice; (3) no effects on activity of adenylate cyclase; (4) decreased activity of cyclic AMP-phosphodiesterase in young mice only; (5) decreased activity of Ca2+, Mg2+-ATPase in the old mice only. The only changes found in striata from morphine-tolerant mice when compared with age-matched controls were elevations in cyclic GMP-phosphodiesterase activities in all three age groups. Differences in control values of the three age groups were as follows: CaM levels, mature greater than old greater than young; Ca2+, Mg2+-ATPase activity, old greater than mature-young. The results indicate age-induced changes in cellular regulation and biochemical responses to morphine.

The uptake of 45Ca was measured in slices of kidney cortex from normal rats, streptozotocin-diabetic rats, and streptozotocin-diabetic rats treated early and late with insulin. Insulin therapy was performed such that blood glucose levels were controlled in half the treated diabetic animals but not in the others. Considerably earlier than evidence of nephropathy (i.e., proteinuria and increased BUN levels) in streptozotocin-diabetic rats, there was a significant decrease in active uptake of calcium by the kidney. Insulin therapy, begun immediately upon diagnosis of diabetes, maintained normal calcium transport even when blood glucose levels were not controlled. On the other hand, insulin therapy, begun 1 mo after diabetes was confirmed but before evidence of nephropathy, did not restore calcium transport to normal whether or not blood glucose was controlled. We conclude that this biochemical mechanism, which possibly may be implicated in the pathophysiology of diabetic nephropathy, is clearly influenced by duration of insulin deficiency and not by the degree in hyperglycemia.

Numerous studies have suggested a role for the nervous system in renal function. Several cholinergic agents have been examined for effects in vivo and in renal slices. Effects mediated through the vascular system and also direct effects have been reported. In this study an irreversible cholinesterase inhibitor, diisopropylfluorophosphate (DFP) in doses of 1-4 mg/kg, was tested on renal function. A single dose of DFP (2, 3 or 4 mg/kg) caused an increased flow of urine of low osmolality over the 6 h after the administration of the drug with essentially a return to control status by 24 h after either of the lower doses. Twenty-four hours after 4 mg/kg, urine volume was less and urine osmolality greater than control. Renal and brain cholinesterases remained depressed 24 h after DFP. In acute experiments on anesthetized animals, inulin clearance was increased by the lower doses and decreased by the highest dose of DFP. Renal blood flow measured with an electromagnetic flow meter showed a similar dose-response relationship. However, urine flow increased at all doses. The increased urine flow associated with decreased inulin clearance (4 mg/kg) and renal blood flow (3 or 4 mg/kg) suggest a direct effect of DFP on renal tubular function. These effects do not appear to be related to inhibition of cholinesterase.

Mature adult (3-6 months old) and aged (24-27 months old) male ICR mice were injected with 10 to 100 mg/kg morphine, SC. The ED50 values for locomotor behavior representing 5 times control activity were 7.5 mg/kg for aged mice and 17.8 mg/kg for the mature adults. There were striking age- and dose-dependent differences in both intensities and durations of morphine-induced locomotor activity. The ED50 values for antinociception 1 hour after morphine administration were 70 mg/kg for the aged mice and 13 mg/kg for the mature adults. One hour after injecting 30 and 100 mg/kg morphine tagged with 3H-morphine, 0.13 and 0.14 percent of the doses appeared in brains of aged and mature adult mice, respectively. Distribution of morphine among brain regions was the same for both age groups. The results suggest that the differences in response to morphine by the two age groups were due to age-related differences in affinities, numbers and/or functioning of opioid receptors and not to pharmacokinetic differences.

Single s.c. injection of 1, 2, 3 or 4 mg/kg of DFP in saline was given to male rats. Control rats received saline. Beginning 24 hr after injections, body weights and food and water consumption were measured at 24 hr intervals. The 1 and 2 mg/kg DFP-treated group maintained these parameters at levels equal to those of the controls. The other DFP-treatment groups showed significant depressions in body weights and in food and water consumption, but these groups recovered 48 and 72 hrs after DFP administration of 3 mg/kg or 4 mg/kg, respectively. Daily injections of 2, 3 or 4 mg/kg of DFP, s.c., caused significant depressions of all three parameters, with only 75% of the 2 mg/kg group showing recovery over the 14 day treatment period. Of the 2 mg/kg group, 25% died following the 6th injection, 100% of the 3 mg/kg group were dead following the 4th injection and 100% of the 4 mg/kg group were dead following the 3rd injection. Prior to deaths in all DFP-treatment groups, the decreases in body weights and in food and water consumption were progressive and dose-dependent. The data show dose-dependency of general toxicity during acute and subacute exposure to DFP and of tolerance during subacute exposure.

A regimen of low-dose preoperative radiation therapy (RT), surgery, and elective postoperative RT for resectable carcinomas of the rectum and rectosigmoid is presented. Initial results in a group of 36 patients is discussed. In four patients clinically silent metastatic disease was discovered. Of 16 patients without indications for postoperative RT, only one died with disease. Indications for postoperative irradiation were found in 15 patients and four relapses (26%) subsequently occurred. Since the surgicopathologic stage of the tumor is the best prognostic predictor for rectal cancer, this regimen allows for the delivery of high-dose adjuvant irradiation only to those at high risk of local recurrence. Thus, this combination selects patients likely to benefit from postoperative RT while preserving the advantages of preoperative RT.