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The ornithine decarboxylase-1 (ODC1) polymorphism at position +316 affects binding by transcriptional activators and repressors and modulates the risk of metachronous colorectal adenomas, particularly in association with aspirin use. We investigated the effects of ODC1 after treatment with difluoromethylornithine (eflornithine)/sulindac or placebo. Two hundred twenty-eight colorectal adenoma patients in a randomized phase III trial were genotyped for ODC1. We used Wilcoxon rank sums tests on non-normally distributed continuous variables across two genotype groups, χ2 or Fisher exact test to assess the association between baseline categorical variables and genotype group, and log binomial regression for the primary (adenoma recurrence) and secondary outcomes (tissue polyamine response, cardiovascular toxicity, gastrointestinal toxicity, and ototoxicity). All statistical tests were two-sided. In binomial regression models with variables age, sex, race, aspirin use, treatment, and ODC1 genotype, treatment was the only statistically significant factor associated with differences in adenoma recurrence or tissue polyamine response. A statistically significant interaction was detected between ODC1 genotype and treatment with respect to adenoma recurrence (placebo group: GG, 50%, AA/GA: 34%; treatment group: GG, 11%, AA/GA, 21%; Pinteraction = .038). Excess ototoxicity was observed among ODC1 AA patients receiving treatment, but the interaction of genotype and treatment on ototoxicity was not statistically significant (P = .45). [ABSTRACT FROM PUBLISHER]

Hepatic Steatosis in Rats Fed Diets with Varying Concentrations of Sucrose. BACON, B. K., PARK, C. H., FOWELL, E M., AND MCLAREN, C. E (1984). . 4, 819–826. The role of dietary sucrose concentrations in the development of hepatic steatosis in rats was investigated. Twelve groups of weanling male Sprague-Dawky rats received semipurified diets with different sucrose concentrations ranging from 20 to 50% (w/w); one group received a cereal-based chow diet Rats were sacrificed after 3 weeks and body weight, liver/body weight ratio, plasma alanine aminotransferase concentration, hepatic triglyceride concentration, and liver morphology (light and electron microscopy) were determined. Body weight and liver/body weight ratio were decreased in rats receiving 40–50 or 25–35% dietary sucrose compared to rats receiving 20% sucrose or chow. Plasma alanine aminotransferase concentrations were within normal limits. Hepatic triglyceride concentration was significantly increased in rats receiving 40–50 and 25–35% dietary sucrose compared to rats receiving 20% dietary sucrose or chow. Light microscopy showed hepatic steatosis in a periportal distribution at all concentrations of dietary sucrose. Both the frequency and the severity of the steatosis were increased with increasing dietary sucrose concentrations. Electron microscopy from selected livers with increased hepatic triglyceride concentrations revealed increased lipid spheres and increased smooth endoplasmic reticulum without prominent Golgi apparatus or GERL complex. It is concluded that high dietary sucrose concentrations are responsible for the development of hepatic steatosis. Semipurified diets with high dietary sucrose concentrations such as the AIN-76A diet (50% sucrose) should not be used in animal studies in which increased trigtyceride deposition could influence experimental outcome. [ABSTRACT FROM PUBLISHER]

The article discusses a randomized placebo-controlled trial that compared the effects of celecoxib and placebo in patients with 10 to 40 actinic keratoses and Fitzpatrick sun-reactive skin types I, II or III, by Elmets and colleagues, published within the issue. The trial showed that celecoxib treated and prevented the progression of lesions at the late stage of cutaneous carcinogenesis. The authors claim that the trial offered addition information on chemoprevention.

Objective: To quantitatively measure tissue composition and hemodynamics during resuscitative endovascular balloon occlusion of the aorta (REBOA) in two tissue compartments using non-invasive two-channel broadband diffuse optical spectroscopy (DOS).Methods: Tissue concentrations of oxy- and deoxyhemoglobin (HbO2 and HbR), water, and lipid were measured in a porcine model (n = 10) of massive hemorrhage (65% total blood volume over 1 h) and 30-min REBOA superior and inferior to the aortic balloon.Results: After hemorrhage, hemoglobin oxygen saturation (StO2 = HbO2/[HbO2 + HbR]) at both sites decreased significantly (-29.9% and -42.3%, respectively). The DOS measurements correlated with mean arterial pressure (MAP) (R2 = 0.79, R2 = 0.88), stroke volume (SV) (R2 = 0.68, R2 = 0.88), and heart rate (HR) (R2 = 0.72, R2 = 0.88). During REBOA, inferior StO2 continued to decline while superior StO2 peaked 12 min after REBOA before decreasing again. Inferior DOS parameters did not associate with MAP, SV, or HR during REBOA.Conclusions: Dual-channel regional tissue DOS measurements can be used to non-invasively track the formation of hemodynamically distinct tissue compartments during hemorrhage and REBOA. Conventional systemic measures MAP, HR, and SV are uncorrelated with tissue status in inferior (downstream) sites. Multi-compartment DOS may provide a more complete picture of the efficacy of REBOA and similar resuscitation procedures. [ABSTRACT FROM AUTHOR]