Prevalence and risk of colorectal neoplasia in consumers of alcohol in a screening population

BACKGROUND AND AIMS: Although studies suggest a positive association between alcohol consumption and risk for colorectal neoplasia, the impact on screening has not been fully examined. It is also unclear whether all types of alcohol are associated with an increased risk. We performed a cross-sectional study to examine the impact of regular alcohol consumption on the detection of significant colorectal neoplasia in a screening population. METHODS: Data collected for 2,291 patients presenting for screening colonoscopy: known risk factors for colorectal neoplasia and alcohol drinking pattern. Our outcome was the endoscopic detection of significant colorectal neoplasia, which included adenocarcinoma, high-grade dysplasia, villous tissue, adenomas 1 cm or greater and multiple (>2) adenomas of any size. RESULTS: When compared to abstainers, we found an increased risk for significant neoplasia in those patients who consumed more than eight drinks of spirits alcohol (26.3%; OR = 2.53; 95% CI = 1.10-4.28; p < 0.01) and those who drank more than eight servings of beer per week (21.7%; OR = 2.43; 95% CI = 1.11-5.32; p= 0.02). Consuming one to eight glasses of wine per week was associated with a decreased risk for significant neoplasia (OR = 0.55; 95% CI = 0.34-0.87; p < 0.01). CONCLUSIONS: While there was a more than twofold increased risk of significant colorectal neoplasia in people who drink spirits and beer, people who drank wine had a lower risk. In our sample, people who drank more than eight servings of beer or spirits per week had at least a one in five chance of having significant colorectal neoplasia detected by screening colonoscopy.     

Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor

OBJECTIVE: The aim of this study was to assess the rate of upper gastrointestinal (UGI) ulcer complications (bleeding, perforation, or gastric outlet obstruction) associated with celecoxib, a specific COX-2 inhibitor, compared with the rate associated with nonspecific, nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: A pooled analysis was conducted of 14 multicenter, double-blind, randomized, controlled trials (RCTs) and a separate analysis of one long-term open label trial that assessed the efficacy and safety of celecoxib for symptomatic treatment of arthritis. The RCTs enrolled 11,008 patients with osteoarthritis or rheumatoid arthritis treated for 2-24 wk; the long-term open label trial enrolled 5,155 patients receiving celecoxib for a maximum of 2 yr. In the RCTs, patients were randomly assigned to receive placebo (n = 1,864; 208 patient-years), celecoxib 25-400 mg b.i.d. (n = 6,376; 1,020 patient-years), or a comparator NSAID (n = 2,768; 535 patient-years); NSAIDs were naproxen 500 mg b.i.d., diclofenac 50 or 75 mg b.i.d., or ibuprofen 800 mg t.i.d.). In the long-term, open-label trial, patients received celecoxib 100-400 mg b.i.d. for up to 2 yr (n = 5,155; 5,002 patient-years). The principal outcome measure of this analysis was development of a UGI ulcer complication, which was prospectively defined as bleeding, perforation, or gastric outlet obstruction. Ulcer complications were assessed and adjudicated by persons blinded to the patient's treatment assignment or the study in which the patient participated. RESULTS: In the RCTs, UGI ulcer complications occurred in no placebo patients (0 of 1,864 patients), in 2 of 6,376 celecoxib patients (0.03%), and in 9 of 2,768 patients receiving an NSAID (0.33%), corresponding to annual incidences of 0.20% for celecoxib (p > 0.05 vs placebo) and 1.68% for NSAIDs (p = 0.002 vs celecoxib and placebo). In the long-term open-label trial, nine UGI ulcer complications occurred, for an incidence of 0.17% and an annualized incidence of 0.18%. CONCLUSIONS: The incidence of UGI ulcer complications associated with celecoxib was 8-fold lower than with nonspecific NSAIDs. The incidence of ulcer complications observed in celecoxib-treated patients was similar to that in patients receiving placebo in the RCTs, and to that in non-NSAID users reported in the literature.     

Identification of severe coronary artery disease using simple clinical parameters.

The purpose of our study was to examine the ability of clinical and resting electrocardiographic variables to provide useful estimates of the probability of three-vessel or left-main coronary artery disease. The study group consisted of 680 patients with symptomatic coronary artery disease who underwent exercise equilibrium radionuclide angiography and coronary angiography within 6 months. Sixteen clinical and electrocardiographic variables were examined by logistic regression analysis. The independently predictive variables were then used to develop convenient graphic estimates of the probability of three-vessel or left-main disease and to classify patients into high-risk (greater than 35%), intermediate-risk (15-35%), or low-risk (less than 15%) groups. Five variables were independently predictive of left-main or three-vessel disease: age, typical angina, diabetes, gender, and both history and electrocardiographic evidence of a prior myocardial infarction. A single graph was constructed that displayed the probability of severe coronary artery disease as a function of a five-point cardiac risk scale, which incorporated these variables. Two hundred sixty-two patients (39% of the study group) were classified as high risk; 127 of these patients (48%) had three-vessel or left-main disease. An additional 96 patients were classified as low risk; nine of these patients (9%) had three-vessel or left-main disease. Five clinical variables that were obtained on an initial patient assessment can provide useful estimates of the likelihood of severe coronary disease.     

Pleiotropic activities of human interferons are mediated by multiple response pathways.

Among the pleiotropic effects of human interferon are the inhibition of viral replication, the activation of natural killer cells, and the inhibition of cellular growth. Oxyphenbutazone, a nonsteroidal antiinflammatory agent, is a potent inhibitor of the antiviral activity of human alpha and beta interferons as determined by cytopathic effect and vesicular stomatitis virus synthesis and release in human foreskin fibroblasts. The inhibition of interferon activity is dose dependent with maximal inhibition at 25-50 microM and minimal inhibition at 1 microM. In contrast, oxyphenbutazone at concentrations as high as 100 microM has no effect on the activation of natural killer cells by human interferon. Similarly, oxyphenbutazone has no inhibitory effect on interferon-induced antigrowth activity in the human breast carcinoma cell line MDA-MB-231. This cell line is sensitive to oxyphenbutazone inhibition of interferon-induced antiviral activity in vitro. In another human cell line, the vulvar carcinoma A431, oxyphenbutazone apparently augments the antigrowth activity of interferon. Although oxyphenbutazone inhibits the fatty acid cyclooxygenase enzyme in these systems, other inhibitors of cyclooxygenase fail to inactivate the antiviral activity of human interferon. Thus, oxyphenbutazone appears to inhibit the interferon antiviral cascade at a site distinct from prostaglandin biosynthesis. Moreover, the failure to inhibit natural killer cell activation or cellular antigrowth effects of human interferon suggests a pathway different from that associated with the antiviral effect of human interferon.     

Comparison of 1-hour and 24-hour blood pressure recordings in central or peripheral baroreceptor-denervated rats

We compared the mean arterial pressure and heart rate activity of conscious, unrestrained rats during 1-hour and 24-hour continuous recording sessions, 3 to 4 weeks after either sinoartic denervation, placement of electrolytic lesions in the nucleus tractus solitarii, or sham operations. Sinoaortic denervation and nucleus tractus solitarii lesions both eliminated the reflex bradycardia to a phenylephrine-induced pressor response. No difference was found in the average level and lability of the mean arterial pressure between 1-hour and 24-hour recordings for any group. No elevation in the average mean arterial pressure of rats with nucleus tractus solitarii lesions was observed, although a mild hypertension was noted in half the sinoarotic-denervated rats, while the other half were normotensive. Group differences were not found for heart rate or heart rate variability; however, 24-hour recordings yielded significantly higher values than 1-hour recordings for all groups. Both medullary lesions and sinoaortic denervation significantly increased the lability of the mean arterial pressure, but the magnitude of the increase was significantly greater in the rats with lesions. The lability of the mean arterial pressure in sinoaortic-denervated rats depended largely on movement-related depressor responses that produced a negative skew in the frequency distribution of their mean arterial pressure. Rats with nucleus tractus solitarii lesions exhibited both pressor and depressor responses that resulted in pressure distributions that had a slight positive skew similar to that displayed by control rats. It is concluded that short-term continuous recordings of mean arterial pressure and heart rate accurately estimate the altered cardiovascular activity of baroreceptor-denervated rats. The differences in the cardiovascular responses of central and peripheral baroreceptor-denervated rats are believed to be due to the more extensive destruction by nucleus tractus solitarii lesions of central neurons and pathways involved in cardiovascular regulation.     

Rescue of CardioSEAL PFO closure device malposition with Amplatzer PFO closure device at time of initial implantation.

This case report describes a patient undergoing patent foramen ovale (PFO) closure for recurrent transient ischemic attacks. A CardioSEAL device was placed, but immediately prolapsed into the left atrium in an unstable position. We describe a novel percutaneous technique that allowed capture of the CardioSEAL device and closure of the PFO.     

Fall-off in Reporting Life Events: Effects of Life Change,Desirability, and Anticipation

Abstract

The influence of event characteristics on recall was examined by directly comparing fall-off in reporting life events as a function of life change, desirability, and anticipation. We collected information from a sample of 1,669 blue-collar workers on stressful life events that occurred in a 1-year interval before the questionnaire was administered. The results indicated no fall-off in reporting events associated with marked life changes (ie, salient events). In contrast, significant fall-off was observed for events characterized by varying degrees of desirability and anticipation. Although ratings of desirability and saliency were not independent, saliency of life events emerged as the dimension most closely associated with accuracy of event reporting. Research on the reliability of measures of life events and the association between event characteristics and illness should consider the kinds of systematic reporting differences observed here.     

Cancer‐associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse‐strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage

Our group recently described recurrent somatic mutations of the miRNA processing gene DICER1 in non‐epithelial ovarian cancer. Mutations appeared to be clustered around each of four critical metal‐binding residues in the RNase IIIB domain of DICER1. This domain is responsible for cleavage of the 3′ end of the 5p miRNA strand of a pre‐mRNA hairpin. To investigate the effects of these cancer‐associated 'hotspot' mutations, we engineered mouse DICER1‐deficient ES cells to express wild‐type and an allelic series of the mutant DICER1 variants. Global miRNA and mRNA profiles from cells carrying the metal‐binding site mutations were compared to each other and to wild‐type DICER1. The miRNA and mRNA profiles generated through the expression of the hotspot mutations were virtually identical, and the DICER1 hotspot mutation‐carrying cells were distinct from both wild‐type and DICER1‐deficient cells. Further, miRNA profiles showed that mutant DICER1 results in a dramatic loss in processing of mature 5p miRNA strands but were still able to create 3p strand miRNAs. Messenger RNA (mRNA) profile changes were consistent with the loss of 5p strand miRNAs and showed enriched expression for predicted targets of the lost 5p‐derived miRNAs. We therefore conclude that cancer‐associated somatic hotspot mutations of DICER1, affecting any one of four metal‐binding residues in the RNase IIIB domain, are functionally equivalent with respect to miRNA processing and are hypomorphic alleles, yielding a global loss in processing of mature 5p strand miRNA. We further propose that this resulting 3p strand bias in mature miRNA expression likely underpins the oncogenic potential of these hotspot mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Influence of oxygen tension on the viscoelastic behavior of red blood cells in sickle cell disease

Although the rheological behavior of sickle cell suspensions and of hemoglobin S solutions is known to be strongly dependent on oxygen tension (PO2), little data exist concerning the influence of PO2 on the viscoelasticity of individual HbSS RBC. We have used micropipette aspiration techniques to test the deformation response of both HbSS and control HbAA RBC over a wide range of PO2 at 23 degrees C. Sickled, spiculed HbSS cells were present for PO2 approximately less than 35 mm Hg; for a number of these cells, the deformation response was essentially elastic and an effective membrane rigidity (EMR) was calculated. EMR increased with decreasing PO2 and was approximately 5 to 50 times higher than the equivalent rigidity of oxygenated HbSS RBC. In addition, the rate of membrane deformation was very slow for sickled cells; the half-time for the deformation process increased as PO2 was lowered and was about two orders of magnitude longer than the equivalent time for normal RBC. Other sickled cells exhibited plastic deformation when subjected to comparable deforming forces and experienced irreversible membrane deformation and budding. At all PO2 levels tested, some HbSS RBC remained as discocytes; these cells had normal membrane elasticity and membrane viscosity. Furthermore, changes in PO2 did not affect the membrane properties of HbAA RBC. Thus, gross abnormalities in the deformation response of HbSS RBC were only detected after morphological sickling had occurred. These abnormalities most likely arose from changes in the cytoplasmic HbS viscoelasticity and, if present in vivo, would be expected to impair the flow of HbSS cells in the microcirculation.