Maria E. Velez

Glutathione deficiency in alcoholics: risk factor for paracetamol hepatotoxicity.

Patients chronically abusing ethanol are more susceptible to the hepatotoxic effects of paracetamol. This could be due to an increased activation of the drug to a toxic metabolite or to a decreased capacity to detoxify the toxic metabolite by conjugation with glutathione (GSH). To test these hypotheses paracetamol 2 g was administered to five chronic alcoholics without clinical evidence of alcoholic liver disease and five control subjects. The urinary excretion of cysteine- plus N-acetyl-cysteine-paracetamol, the two major products of detoxification of the reactive metabolite of paracetamol, was not significantly higher in chronic alcoholics arguing against a substantially increased metabolic activation of paracetamol. Chronic alcoholics had significantly lower plasma concentrations of GSH than healthy volunteers, however (4.35 (1.89) microM v 8.48 (2.68) microM, p less than 0.05) before the administration of paracetamol, and plasma GSH reached lower concentrations in the alcoholics after paracetamol (2.40 (1.36) v 6.26 (2.96) microM). In a group of patients with alcoholic hepatitis intrahepatic GSH was significantly lower than in patients with chronic persistent hepatitis and patients with non-alcoholic cirrhosis, suggesting that low plasma GSH in alcoholics reflects low hepatic concentrations of GSH. The data indicate that low GSH may be a risk factor for paracetamol hepatotoxicity in alcoholics because a lower dose of paracetamol will be necessary to deplete GSH below the critical threshold concentration where hepatocellular necrosis starts to occur.

Visceral abdominal obesity measured by CT scan is associated with an increased risk of Barrett's oesophagus: a case-control study

Objective Abdominal obesity has been associated with increased risk of Barretts oesophagus (BE) but the underlying mechanism is unclear. We examined the association between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and the risk of BE. Design A case-control study among eligible patients scheduled for elective oesophagastroduodenoscopy (EGD) and in a sample of patients eligible for screening colonoscopy recruited at the primary care clinic. All cases with definitive BE and a random sample of controls without BE were invited to undergo standardised mid-abdomen non-contrast computerised axial tomography images, which were analysed by semiautomated image segmentation software. The effect of VAT and SAT surface areas and their ratio (VAT to SAT) on BE were analysed in logistic regression models. Results A total of 173 BE cases, 343 colonoscopy controls and 172 endoscopy controls underwent study EGD and CT scan. Participants with BE were more than twice as likely to be in the highest tertile of VAT to SAT ratio (OR: 2.42 (1.51 to 3.88) and adjusted OR 1.47 (0.88 to 2.45)) than colonoscopy controls, especially for those long (≥3 cm) segment BE (3.42 (1.67 to 7.01) and adjusted OR 1.93 (0.92 to 4.09)) and for white men (adjusted OR 2.12 (1.15 to 3.90)). Adjustment for gastroesophageal reflux disease (GERD) symptoms and proton pump inhibitors (PPI) use attenuated this association, but there was a significant increase in BE risk even in the absence of GERD or PPI use. Conclusions Large amount of visceral abdominal fat relative to subcutaneous fat is associated with a significant increase in the risk of BE. GERD may mediate some but not all of this association.

Waist-to-Hip Ratio, but Not Body Mass Index, Is Associated With an Increased Risk of Barrett's Esophagus in White Men

BACKGROUND & AIMS Abdominal obesity increases the risk of gastroesophageal reflux disease (GERD) and also might contribute to the development of Barretts esophagus (BE), although results are inconsistent. We examined the effects of waist-to-hip ratio (WHR) and body mass index (BMI) on the risk of BE and investigated whether race, GERD symptoms, or hiatus hernia were involved. METHODS We conducted a case-control study using data from eligible patients who underwent elective esophagogastroduodenoscopy; 237 patients had BE and the other 1021 patients served as endoscopy controls. We also analyzed data and tissue samples from enrolled patients who were eligible for screening colonoscopies at a primary care clinic (colonoscopy controls, n = 479). All patients underwent esophagogastroduodenoscopy, completed a survey, and had anthropometric measurements taken. WHR was categorized as high if it was 0.9 or greater for men or 0.85 or greater for women. Data were analyzed with logistic regression. RESULTS There was no association between BMI and BE. However, more patients with BE had a high WHR (92.4%) than endoscopy controls (79.5%) or colonoscopy controls (84.6%) (P < .001 and P = .008, respectively). In adjusted analysis, patients with BE were 2-fold more likely to have a high WHR than endoscopy controls (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.1-3.5), this association was stronger for patients with long-segment BE (OR, 2.81; 95% CI, 1.0-7.9). A high WHR was associated significantly with BE only in whites (OR, 2.5; 95% CI, 1.2-5.4), but not in blacks or Hispanics. GERD symptoms, hiatus hernia, or gastroesophageal valve flap grade could not account for the association. CONCLUSIONS High WHR, but not BMI, is associated with a significant increase in the risk of BE, especially long-segment BE and in whites. The association is not caused by GERD symptoms or hiatus hernia.

Using a multifaceted approach to improve the follow-up of positive fecal occult blood test results.

OBJECTIVES:Inadequate follow-up of abnormal fecal occult blood test (FOBT) results occurs in several types of practice settings. Our institution implemented multifaceted quality improvement (QI) activities in 2004–2005 to improve follow-up of FOBT-positive results. Activities addressed precolonoscopy referral processes and system-level factors such as electronic communication, provider education, and feedback. We evaluated their effects on timeliness and appropriateness of positive-FOBT follow-up and identified factors that affect colonoscopy performance.METHODS:Retrospective electronic medical record review was used to determine outcomes before and after QI activities in a multispecialty ambulatory clinic of a tertiary care Veterans Affairs facility and its affiliated satellite clinics. From 1869 FOBT-positive cases, 800 were randomly selected from time periods before and after QI activities. Two reviewers used a pretested standardized data collection form to determine whether colonoscopy was appropriate or indicated based on predetermined criteria and if so, the timeliness of colonoscopy referral and performance before and after QI activities.RESULTS:In cases where a colonoscopy was indicated, the proportion of patients who received a timely colonoscopy referral and performance were significantly higher post-implementation (60.5% vs. 31.7%, P<0.0001 and 11.4% vs. 3.4%, P=0.0005). A significant decrease also resulted in median times to referral and performance (6 vs. 19 days, P<0.0001 and 96.5 vs. 190 days, P<0.0001) and in the proportion of positive-FOBT test results that had received no follow-up by the time of chart review (24.3% vs. 35.9%, P=0.0045). Significant predictors of absence of the performance of an indicated colonoscopy included performance of a non-colonoscopy procedure such as barium enema or flexible sigmoidoscopy (OR=16.9; 95% CI, 1.9–145.1), patient non-adherence (OR=33.9; 95% CI, 17.3–66.6), not providing an appropriate provisional diagnosis on the consultation (OR=17.9; 95% CI, 11.3–28.1), and gastroenterology service not rescheduling colonoscopies after an initial cancellation (OR=11.0; 95% CI, 5.1–23.7).CONCLUSIONS:Multifaceted QI activities improved rates of timely colonoscopy referral and performance in an electronic medical record system. However, colonoscopy was not indicated in over one third of patients with positive FOBTs, raising concerns about current screening practices and the appropriate denominator used for performance measurement standards related to colon cancer screening.

Helicobacter pylori-negative gastritis: prevalence and risk factors.

OBJECTIVES:Recent studies using histology alone in select patients have suggested that Helicobacter pylori-negative gastritis may be common. The objective of this study was to investigate the prevalence of H. pylori among individuals with histologic gastritis.METHODS:Subjects between 40 and 80 years underwent elective esophagogastroduodenoscopy at a VA Medical Center. Gastric biopsies were mapped from seven prespecified sites (two antrum, four corpus, and one cardia) and graded by two gastrointestinal pathologists, using the Updated Sydney System. H. pylori-negative required four criteria: negative triple staining at all seven gastric sites, negative H. pylori culture, negative IgG H. pylori serology, and no previous treatment for H. pylori. Data regarding tobacco smoking, alcohol drinking, nonsteroidal anti-inflammatory drug, and proton pump inhibitor (PPI) use were obtained by questionnaire.RESULTS:Of the 491 individuals enrolled, 40.7% (200) had gastritis of at least grade 2 in at least one biopsy site or grade 1 in at least two sites. Forty-one (20.5%) had H. pylori-negative gastritis; most (30 or 73.2%) had chronic gastritis, five (12.2%) had active gastritis, and six (14.6%) had both. H. pylori-negative gastritis was approximately equally distributed in the antrum, corpus, and both antrum and corpus. Past and current PPI use was more frequent in H. pylori-negative vs. H. pylori-positive gastritis (68.2% and 53.8%; P=0.06).CONCLUSIONS:We used multiple methods to define non-H. pylori gastritis and found it in 21% of patients with histologic gastritis. While PPI use is a potential risk factor, the cause or implications of this entity are not known.

Association between Helicobacter pylori and Barrett's esophagus: a case-control study.

OBJECTIVES:The estimated association between Helicobacter pylori and Barretts esophagus (BE) has been heterogenous across previous studies. In this study, we aimed to examine the association between H. pylori and BE and to identify factors that may explain or modify this association.METHODS:We conducted a case–control study in which we used screening colonoscopy controls recruited from primary care clinics as our primary control group in order to minimize selection bias. All participants underwent an esophagogastroduodenoscopy with gastric mapping biopsies. We used logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the association between H. pylori and BE while controlling for confounders.RESULTS:We identified 218 cases and 439 controls. The overall OR for the association between H. pylori and BE after controlling for age and white race was 0.55 (95% CI: 0.35–0.84). We observed an even stronger inverse association (OR: 0.28; 95% CI: 0.15, 0.50) among participants with corpus atrophy or antisecretory drug use ≥1 time per week (factors thought to lower gastric acidity), and no inverse association in patients without these factors (OR: 1.32; 95% CI: 0.66, 2.63).CONCLUSIONS:The association between H. pylori and a decreased risk for BE appears to occur in patients with factors that would likely lower gastric acidity (corpus atrophy or taking antisecretory drugs at least once a week).

Interaction of Alcohol and Hepatitis C Virus Infection on Severity of Liver Disease

Chronic alcoholics have a high prevalence ofhepatitis C virus (HCV) infection. The present study wascarried out to examine the association between HCVinfection and alcohol abuse, and the influence of these factors on the severity of liver disease.Patients with history of heavy alcohol abuse (≥80 gof ethanol per day for ≥5 years) were analyzed withrespect to the amount of alcohol use, clinical evidence of liver disease, and laboratory tests. Onehundred ninety-nine patients, 137 HCV positive and 62HCV negative were included in the study. HCV-infectedsubjects had liver disease for a longer duration (P < 0.0001) and had higher incidence ofsymptoms of hepatic decompensation in the past comparedto uninfected alcoholics. Several differences were notedbetween the two groups at the time of presentation to the hospital. Alcoholics with HCV infectionhad lower daily alcohol consumption (P < 0.001), wereabstinent for a longer duration (P < 0.02) and hadlower lifetime use of ethanol (P < 0.005) compared to HCV-negative subjects. Assessmentof liver tests showed greater derangement in uninfectedalcoholics compared to HCV-positive subjects. Thepresent study shows that HCV-infected chronic alcoholics have lower alcohol consumption and, perhaps asa consequence, have less severe liver disease comparedto HCV-negative individuals. These findings suggest thatin chronic alcoholics, despite the presence of HCV infection, the severity of liver damageis related to the amount of alcoholconsumption.

Influence of Chronic Alcohol Abuse on Hepatitis C Virus Replication

Background: Patients with alcoholic liver disease have a high prevalence of hepatitis C virus (HCV) infection. Several workers have shown that HCV-infected alcoholics have more severe biochemical and histological evidence of liver disease than anti-HCV-negative patients. One possible mechanism for the increased liver damage is that alcohol may have a stimulatory effect on HCV replication. The present study was carried out to examine this issue in detail. Methods: Sixty-eight HCV-infected patients, comprising of 50 chronic alcoholics, consuming 80 g or more of alcohol daily for at least 5 years, and 18 completely abstinent subjects were included in the study. Quantitative HCV-RNA was performed by the branched chain DNA (bDNA) technique. Results: There was no significant difference in the mean serum HCV titers in chronic alcoholics compared to nonalcoholic subjects. Linear regression analysis showed no correlation between the daily ethanol consumption and HCV titers. Seven of the chronic alcoholics, 4 of whom were continuing to drink and 3 who had become abstinent, were retested after 6 months. There was no definite trend in the viral titers, either in abstinent individuals or in those who continued to drink. Conclusions: These findings suggest that chronic alcohol abuse does not influence the HCV load in the serum. Therefore, the observation that alcoholics with HCV infection have more severe liver damage requires some other explanation than increased HCV viral titers.

The Prevalence of Helicobacter pylori Remains High in African American and Hispanic Veterans

Helicobacter pylori in the United States has been declining in the 1990s albeit less so among blacks and Hispanics. As the socioeconomic status of racial groups has evolved, it remains unclear whether the prevalence or the racial and ethnic disparities in the prevalence of H. pylori have changed.

Delivered volumes of enteral nutrition exceed prescribed volumes.

BACKGROUND Enteral nutrition (EN) provisions are typically calculated based on a 24-hour infusion period. However, feedings are often interrupted for daily activities, procedures, or gastrointestinal intolerance. The studys objective was to determine the delivered EN quantities provided to stable hospitalized patients, using cellular time and measured volumes to verify our EN calculation adjustment. METHODS A supply of consecutively numbered ready-to-hang (RTH) EN product was delivered to the bedside of 26 inpatients with established EN tolerance at goal rates on various types of nursing units. The dietitian weighed the volume remaining in the infusing product and recorded the measurement time. On the following days, the dietitian continued to weigh the infusing RTH product and the empty RTH bottles saved by nursing. The primary outcome was the difference between the prescribed and delivered EN provisions, which was calculated with a paired t test. RESULTS Patients received significantly more calories in the delivered enteral feeding (mean [SD], 1678 [385] kcal) than prescribed calories in the EN order (1489 [246 kcal]; t = 3.736, P = .001), adjusting for observed time. No significant differences were found between nursing units, product, and rate. CONCLUSION EN delivered may actually exceed ordered amounts by 5%-21% (mean, 12%) with feeding pump inaccuracy as the primary contributing factor. This differs from what others have found. Our findings support using a volume-based ordering system vs a rate-based ordering system for more accurate EN delivery.