No abstract

These studies were performed to see if jejunal malabsorption of magnesium in patients with chronic renal disease was influenced by therapy with 1 alpha, 25-dihydroxyvitamin D3 [1,25-(OH)2D3; 2 microgram/day by mouth for 7 days]. This treatment restored normal serum concentrations of the vitamin D metabolite from 0.9 +/- 0.2 to 4.2 +/- 0.6 ng/dl. Jejunal absorption of magnesium, measured by a triple-lumen constant-perfusion technique, was enhanced in each of the seven patients by this therapy. The mean value rose from 0.04 +/- 0.02 to 0.13 +/- 0.02 mmol . 30 cm-1 . h-1. This last value is similar to the magnesium absorption rate in untreated normal subjects. These results demonstrate that magnesium absorption in the human jejunum is dependent on vitamin D, and they show that 1 alpha,25-dihydroxyvitamin D3 therapy in patients with chronic renal failure is associated with an enhanced jejunal absorption of magnesium.

We studied 16 patients with diabetes and fecal incontinence. The onset of incontinence coincided with the onset of chronic diarrhea in most patients. Episodes of incontinence occurred when stools were frequent and loose; however, 24-hour stool weights were usually within normal limits. All patients had evidence of autonomic neuropathy, and one third had steatorrhea. Incontinent diabetics had a lower mean basal anal-sphincter pressure than 35 normal subjects (63 +/- 4 vs. 37 +/- 4 mm Hg; P less than 0.001), reflecting abnormal internal-anal-sphincter function. The increment in sphincter pressure with voluntary contraction (external-sphincter function) was not significantly different from normal. Incontinent diabetics also had impaired continence for a solid sphere and for rectally infused saline. In contrast, 14 diabetics without diarrhea or incontinence had normal sphincter pressures and normal results on tests of continence, even though 79 per cent had evidence of autonomic neuropathy and nearly half had steatorrhea. We conclude that incontinence in diabetic patients is related to abnormal internal-anal-sphincter function, and that as a group, diabetics without diarrhea do not have latent defects in continence.

Aims The purpose of this study was to determine prospectively whether p53 protein accumulation in biopsies of Barrett’s metaplasia (BM) is a predictor of malignant progression, without relying on dysplasia grading. Methods and results Sections of formalin fixed paraffin embedded tissue from the initial biopsies of 275 patients with BM, who had no high grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), were stained for p53 by immunohistochemistry. Mean follow up was 41 months. p53-positive biopsies were divided into 4 groups: scattered positive cells, multifocal scattered positive cells, aggregates of positive cells, and multifocal aggregates of positive cells. Kaplan-Meier analysis with the log-rank test was used to determine the rate of progression to high grade dysplasia (HGD)/esophageal adenocarcinoma (EAC). Of the 275 patients, 227 had initial biopsies completely negative for p53 and of these one (0.4%) progressed to HGD/EAC; none of 24 (0%) patients with scattered positive cells and none of 4 (0%) of patients with multifocal scattered positive cells progressed. By contrast, 5 of 16 (31.25%) patients with aggregates of positive cells and 3 of 4 (75%) of those with multifocal aggregates of positive cells progressed to HGD/EAC. Kaplan-Meier analysis with log rank statistics showed the difference in progression rate between the five groups to be highly significant (p<0.0001). Conclusions We conclude that p53 protein accumulation, detected by IHC in aggregates of cells, is a significant predictor of malignant progression in patients with BM.

Our data strongly suggest that in BM, after oxidative DNA damage, as a result of gastroesophageal reflux, there is an increase in the percentage of cells in the G0G1 or G2M phases of the cell cycle to enable repair of damaged DNA; in some of these cases this is followed sequentially by p53 gene mutation and protein accumulation, DNA aneuploidy, HGD, and CA with or without Glut1 overexpression. These events can be detected in routinely processed biopsy samples.