Absence of a differential induction of cytochrome P450 2E1 by different alcoholic beverages in rats: implications for the aetiology of human oesophageal cancer

Alcohol is an important risk factor for human oesophageal cancer. There is evidence from epidemiological studies that some specific alcoholic drinks, e.g. Calvados apple brandy, are associated with a greater risk than others. Alcohol induces cytochrome P450 2E1 (CYP2E1) and the hypothesis was tested that different alcoholic beverages, containing a variety of alcoholic compounds, could differentially induce expression of cytochrome P450 enzymes. Twelve groups of five rats each were treated for 3 days with different alcoholic beverages (ethanol alone, whisky, farm-produced or commercial Calvados brandy, beer, cider, wine) adjusted to 4, 10 or 20% of ethanol in drinking water. Immunoblotting using a monoclonal antibody specific for rat CYP2E1 revealed a single protein band in liver microsomes. Densitometric quantitation of microsomal proteins demonstrated a significant two-, three- and sixfold increase in band intensity after treatment with ethanol concentrations of 4, 10 and 20% respectively, compared to control rats drinking water alone. There was a dose-dependent increase in liver microsomal metabolism of CYP2E1 substrates (para-nitrophenol and dimethylnitrosamine) in ethanol-treated rats. However, there were no significant differences in the level of CYP2E1 protein or enzymatic activity between the different alcoholic beverages at the same ethanol concentration. There was a slight increase in hepatic CYP1A-related enzymatic activities in the alcohol-treated rats compared to the controls, but no difference between the treated groups either with dose of ethanol or type of beverage. These data show that induction of CYP2E1 with acute alcohol treatment is predominantly determined by the ethanol content of the beverage. Received: 10 February 1997 / Accepted: 26 May 1997     

Efficacy of short‐term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food‐cobalamin malabsorption: A study of 30 patients

Background: It has been suggested that oral cobalamin (vitamin B₁₂) therapy may be an effective therapy for treating cobalamin deficiencies related to food‐cobalamin malabsorption. However, the duration of this treatment was not determined. Patients and method: In an open‐label, nonplacebo study, we studied 30 patients with established cobalamin deficiency related to food‐cobalamin malabsorption, who received between 250 and 1000 μg of oral crystalline cyanocobalamin per day for at least 1 month. Endpoints: Blood counts, serum cobalamin and homocysteine levels were determined at baseline and during the first month of treatment. Results: During the first month of treatment, 87% of the patients normalized their serum cobalamin levels; 100% increased their serum cobalamin levels (mean increase, +167 pg/dl; P < 0.001 compared with baseline); 100% had evidence of medullary regeneration; 100% corrected their initial macrocytosis; and 54% corrected their anemia. All patients had increased hemoglobin levels (mean increase, +0.6 g/dl) and reticulocyte counts (mean increase, +35 × 10⁶/l) and decreased erythrocyte cell volume (mean decrease, 3 fl; all P < 0.05). Conclusion: Our findings suggest that crystalline cyanocobalamin, 250–1000 μg /day, given orally for 1 month, may be an effective treatment for cobalamin deficiencies not related to pernicious anemia.     

In-hospital mortality of surgical patients: is there an empiric basis for standard setting?

Several public and private groups have set minimum procedure-specific volume standards. Such standards reflect concerns about hospital quality and cost. In-hospital mortality rates are often taken as one measure of quality. To learn about variations in in-hospital mortality rates, we analyzed data on patients who underwent any of seven surgical procedures from a national cohort of 521 hospitals observed continuously between 1972 and 1981. On the average, mortality rates fell as the number of procedures performed annually at the hospital rose. Volumes at which mortality rates reached minimum levels were far higher than actual volumes achieved by the vast majority of hospitals. However, knowledge of hospital volumes left the major part of variation among hospitals' procedure-specific mortality rates unexplained. Many hospitals with low volumes of certain procedures had no associated deaths. Hospitals experienced appreciable year-to-year variation in mortality even though mortality rates fell with the number of years the procedure was performed at the hospital. Correlations among mortality rates for the procedures were low, suggesting that variation in rates is procedure rather than hospital specific. State rate-setting programs had no effect on mortality rates associated with the procedures analyzed. For several reasons, we conclude that an adequate statistical basis for setting minimum volume standards does not presently exist.     

Contribution of phlebography in the surgical treatment of chronic venous insufficiency of the lower extremities

In which circumstances does a surgeon request phlebograms and which ones? What is the contribution of phlebography regarding therapeutic indications and surgical technique.     

Conclusions

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Conclusions Conclusions