E2F-1 overexpression correlates with decreased proliferation and better prognosis in adenocarcinomas of Barrett oesophagus.

BACKGROUND: E2F-1 expression is positively associated with tumour growth in oesophageal squamous-cell carcinomas (OSCC), while it exhibits oncosuppressive features in colonic adenocarcinomas (AC). To date there are no data regarding E2F-1 expression and its relationship with tumour kinetics (proliferation, apoptosis) in adenocarcinomas that develop on Barrett oesophagus. AIM: As oesophageal adenocarcinomas occur almost exclusively in the metaplastic Barrett epithelium and the opposing E2F-1 behaviour seems to be cell and tissue-type dependent, we examined the manner in which E2F-1 acts in ACs of Barrett oesophagus. METHODS: We estimated the immunohistochemical expression of E2F-1, Ki-67, caspase-3 and p53 immunohistochemical status in 35 Barrett oesophagus ACs. RESULTS: E2F-1 immunopositivity correlated inversely with Ki-67, by semi-serial section and statistical analysis (p = 0.023, Spearman correlation). Semi-serial section analysis revealed a direct association between E2F-1 and caspase-3 staining. No correlation was found with p53 status. Cases with higher E2F-1 immunoexpression exhibited longer survival (p = 0.047, Cox-regression). CONCLUSIONS: E2F-1 expression was negatively related to tumour proliferation in ACs of Barrett oesophagus. Additionally, E2F-1 immunohistochemical status correlated positively with patient survival. These findings are opposite from those seen in OSCCs, suggesting that the tumour-suppressing E2F-1 behaviour in oesophageal adenocarcinomas is possibly due to the intestinal-type nature of the metaplastic Barrett mucosa.

Evaluation of two prediction models for digoxin dosing.

The relationship between the digoxin elimination parameter (A%) and creatinine clearance (CLCr) was determined, from blood level data of 160 hospital patients receiving digoxin tablets. The linear regression equation obtained, which varied only slightly from that reported by Jelliffee previously, was used to predict serum digoxin concentrations in 140 patients of four age groups (50-60, 60-70, 70-80 and 80-90 years). The predictions made were found to be less biased and more precise, irrespective of the age of the patients, than those produced using another predictive method known as Dobbs method. However, correlation coefficients of predicted versus measured serum digoxin concentrations for each method did not differ significantly and frequency distribution analyses of prediction errors gave poor results (up to 63% only). Therefore, neither method can be considered to be superior to the other nor can they be said to ensure accurate predictions of serum digoxin concentrations.

The in vitro reduction of dimethylpropion.

A study of the in vitro metabolism of dimethylpropion using different tissue homogenates of certain animals showed that: 1. Only the two major metabolites of dimethylpropion, i.e., methylpseudoephedrine and monomethylpropion were formed. 2. Species variation was observed with regard to the reductive ability of the liver homogenates. 3. Anaerobic conditions favored in vitro reduction to form methylpseudoephedrine. 4. The liver-soluble fraction exhibited the highest enzymatic reductive activity toward dimethylpropion. 5. Significant metabolic reduction of dimethylpropion was exhibited by the soluble fraction of the kidney.

The effect of food on the movement of pellets in the gastro-intestinal tract.

The effect of food on the movement of pellets in the gastro-intestinal tract was investigated in seven volunteers, either by means of X-rays taken after oral administration of barium sulfate pellets or by means of saliva concentration profiles of lithium obtained after oral administration of lithium sulfate controlled-release pellets. The X-ray studies showed that food had an effect on the time required for the pellets to leave the stomach and on their degree of dispersion in the small intestine, but not on other parameters. The studies with the lithium sulfate controlled-release pellets showed that food had a significant effect only in one in three subjects.

Evaluation of the percutaneous absorption and metabolism of some aminopropiophenones.

The absorption of diethylpropion (DEP I), dimethylpropion (DMP I) and some of their basic metabolites into and passage through the skin was investigated and a comparison of their metabolism following oral and percutaneous administration made. High percentages (60-80%) of DEP I and its metabolites and a small percentage of DMP I and its metabolites were taken up into the skin in less than 2 min--the remaining percentages of the compounds were absorbed into the skin by a first order process. The rate of appearance of the compounds in the blood, which reflects their rate of passage through the skin, did not correlated with their rate of absorption into the skin. More metabolism occurred with all the compounds after their oral administration than after their percutaneous application.