Our study was undertaken to determine the prognostic significance of several common genetic alterations observed in colorectal carcinomas. We have previously analysed loss of heterozygosity of the MCC, APC, p53 and DCC tumour suppressor gene loci as well as p53 gene mutations and protein over-expression in a series of 100 Dukes' stage B and C colorectal tumours obtained at surgery. To extend our observations of alterations that may occur in these tumours, mutations to the c-Ki-ras oncogene and APC tumour suppressor gene were detected by PCR single-strand conformation polymorphism analysis. Short-term follow-up revealed no significant association between overall patient survival and any single, or combination of, genetic alteration(s). Surprisingly, patients whose tumours showed evidence of p53 protein over-expression/accumulation by immunocytochemistry (ICC) had a significantly better prognosis (p = 0.039) than those whose tumours had no p53 ICC reactivity.

Rectal washout eliminates exfoliated malignant cells in the rectum in the vicinity of the anastomosis.

1. The validity of plasma noradrenaline as an index of sympathetic nervous activity was assessed by estimating variation in individual organ contribution to circulating concentrations.2. Arteriovenous (A-V) differences in noradrenaline and adrenaline concentration were measured across several organs in nine patients with mild essential hypertension, in five with renal artery stenosis and 15 phaeochromocytoma patients.3. In patients with phaeochromocytomas the percentage extraction of noradrenaline and adrenaline (estimated from the A-V differences) was similar across all organs, suggesting that adrenaline extraction could be used as a marker for noradrenaline extraction.4. In the non-tumour patients the A-V difference for noradrenaline was less than that for adrenaline across most organs studied, reflecting the net result of noradrenaline release and extraction. The estimated contribution of various organs to the noradrenaline concentrations in their venous effluent was: heart. 21%; kidney 47%; legs 68%.5. This pattern of A-V difference proved a positive diagnostic feature for non-tumour patients since it was not found even in the patients with small phaeochromocytomas, whose peripheral venous noradrenaline concentration alone did not distinguish them. Correspondence: Dr M. J. Brown, Department of Clinical Pharmacology, Royal Postgraduate Medical School, Du Cane Road, London W12 OHS.6. The venous-arterial difference across the adrenal. glands of non-tumour patients was more than 10-fold greater for adrenaline than that for noradrenaline. Since the mean arterial concentration of noradrenaline was more than fivefold higher than that of adrenaline, the normal adrenal contribution to circulating noradrenaline is likely to be less than 2%. 7. In the patients with renal artery stenosis renal venous concentrations of noradrenaline (from the ischaemic kidney) were higher than arterial values, but mean arterial values were no higher than in the essential hypertensive patients.8. Local variations in sympathetic activity may occur without altering the plasma noradrenaline concentration measured in peripheral plasma.

1. A randomized, controlled trial was carried out to examine whether changes in type and amount of dietary protein were responsible for earlier observations of blood-pressure-lowering effects of lacto-ovo-vegetarian diets. 2. Sixty-four subjects were pair-matched for sex, age, weight and sitting systolic blood pressure, and were randomly allocated to receive one of two types of protein supplement: one containing proteins from meat, the other proteins from non-meat sources. The supplements were balanced in terms of other nutrients. Consumption of other meat, poultry or fish was prohibited. 3. Sitting and standing blood pressures, weight, dietary intakes and plasma and urinary electrolytes were measured at regular intervals during the 12 weeks of trial. Urinary 3-methylhistidine was used as a measure of compliance. 4. Fifty subjects completed the trial. There were no statistically significant blood pressure differences between groups either at baseline or at end-of-trial, neither were there any substantive differences in mean blood pressure changes between baseline and end-of-trial. 3-Methyl-histidine excretion was significantly lower in subjects on the non-meat diet. 5. The results suggest that the protein components of the lacto-ovo-vegetarian diet are not responsible for the blood-pressure-lowering effects of that diet.