Diagnostic yield of colonoscopy to evaluate melena after a nondiagnostic EGD.

BACKGROUND: Melena can be caused by bleeding from lower GI sources. Colonoscopy is frequently used to investigate melena after a nondiagnostic EGD. OBJECTIVE: To determine the diagnostic yield and rate of therapeutic intervention during colonoscopy in patients with melena and a nondiagnostic EGD. DESIGN: Retrospective case-control study. SETTING: Community and academic centers over a diverse geographic area in the United States. PATIENTS: This study involved patients in the Clinical Outcomes Research Initiative database with a colonoscopy performed to investigate melena within 30 days of a nondiagnostic EGD for the same indication. A control group had colonoscopies performed for average-risk screening. MAIN OUTCOME MEASUREMENTS: The endoscopic finding of a suspected bleeding source defined as right-sided arteriovenous malformation, colitis, polyp ≥ 20 mm, tumor, or ulcer. Rate of therapeutic intervention during colonoscopy. RESULTS: Colonoscopy found a suspected bleeding source in 4.8% of patients with melena, more frequently than in the control group (odds ratio [OR] 2.17; 95% confidence interval [CI], 1.65-2.86; P < .0001). The rate of therapeutic intervention during melena-related colonoscopy was 1.7%. Patients with melena were more likely to have a colon tumor (OR 2.87; 95% CI, 1.82-5.51; P < .0001) than were control patients. LIMITATIONS: Retrospective design, conclusions being dependent on the accuracy of database input, and lack of pertinent clinical data (eg, hemoglobin). CONCLUSION: The diagnostic yield of colonoscopy to investigate melena after nondiagnostic EGD is low. The need for therapeutic intervention during colonoscopy for this indication is very low. This population should undergo colonoscopy because they are at increased risk of colorectal cancer. Colonoscopy can potentially be performed electively in stable patients without continued bleeding.

Human response to alpha2-adrenergic agonist stimulation studied in an isolated vascular bed in vivo: Biphasic influence of dose, age, gender, and receptor genotype.

BACKGROUND AND OBJECTIVES: Activation of alpha 2 -adrenergic receptors regulates a broad spectrum of physiologic responses, including blood pressure (centrally and peripherally), sedation, analgesia, insulin release, renal function, cognition, and behavior. The purpose of this study was to explore systematically the local vascular responses in humans triggered by a highly selective alpha 2 -adrenergic agonist (azepexole [B-HT 933]) and whether such responses are dose-dependent or influenced by age, gender, or allelic variation at the drug's receptor. METHODS: We evaluated dorsal hand vein vascular responses to the infusion of a wide spectrum of doses of azepexole, assessing any venodilation, as well as the maximal extent of venoconstriction (B max ) and the dose that produced a half-maximal effect (K d ), in 50 healthy normotensive adults of both genders and 4 ethnicities. Genomic deoxyribonucleic acid from the study subjects was evaluated at polymorphisms of the alpha 2B -adrenergic receptor gene (ADRA2B). RESULTS: We found previously unreported initial venodilation to low doses (10-100 ng/min) of azepexole, followed by progressive, intense venoconstriction to higher doses (200-100,000 ng/min) of the drug. Younger individuals (aged <30 years) had less venodilation than older individuals (aged >30 years) with low doses of azepexole but had a greater extent of venoconstriction at higher doses of azepexole (ANOVA, P = .001). Men had less venodilation than women with low doses of azepexole but greater venoconstriction with higher doses (ANOVA, P = .036). Several common polymorphisms (>10% minor allele frequency) at ADRA2B (insertion/deletion polymorphism [Glu 322-325 ], G-98C, C1182A, and C1776A) did not show an association with either B max or K d for the drug response. The A36G (Thr12Thr) synonymous single nucleotide polymorphism displayed a nonsignificant trend (P = .073) toward higher K d in A/G heterozygotes compared with A/A homozygotes. CONCLUSIONS: Local infusion into the human dorsal hand vein of a highly selective alpha 2 -adrenergic agonist, azepexole, produces biphasic responses, with venodilation at a low dose and intense venoconstriction at a higher concentration. These responses to azepexole show prominent differences as a function of age and gender but appear not to depend on common allelic variations at the ADRA2B receptor.

Assessment and management of low bone density in inflammatory bowel disease and performance of professional society guidelines.

BACKGROUND: Inflammatory bowel disease (IBD) patients have increased prevalence of osteoporosis, leading to guideline recommendations for bone mineral density (BMD) testing. The study aim was to identify predictors of BMD testing and treatment and assess guideline effectiveness to identify IBD patients with osteoporosis. METHODS: Records of all IBD patients at seven medical facilities were reviewed for clinical data and BMD testing from January 1996 through October 2006. RESULTS: A total of 2035 patients had 317 bone density tests performed. Osteopenia was found in 48% of patients, osteoporosis in 26%. Among patients meeting guideline criteria for BMD testing and ≥1 year of follow-up, 23.3% underwent testing. The strongest predictors of testing were menopause (adjusted hazard ratio [AHR] 3.02) and receiving care at a tertiary center (AHR 2.56). Testing rates were low in patients with age ≥60 years, ulcerative colitis, and a history of inpatient IBD treatment. Osteoporotic patients received calcium/vitamin D and bisphosphonates in 59% and 75% of cases, respectively. Osteoporotic males had a 37% rate of hypogonadism. Guideline criteria do not distinguish patients with osteoporosis. The criteria had a sensitivity, specificity, positive predictive value, and negative predictive value of 84%, 23%, 27%, and 81% for osteoporosis in the tested population, respectively. CONCLUSIONS: Osteoporosis is highly prevalent in the IBD population, but BMD testing and osteoporosis treatments are underutilized. Male hypogonadism is common in osteoporotic IBD patients. Guidelines do not identify IBD patients with osteoporosis.

Complications after ERCP in patients with primary sclerosing cholangitis.

BACKGROUND: There are conflicting data regarding the role of ERCP in patients with primary sclerosing cholangitis (PSC) and the risk of procedure-related complications. OBJECTIVE: We compared the complication rate after ERCP in a consecutive series of patients with PSC compared with control patients with biliary strictures who did not have PSC. DESIGN: Retrospective cross-sectional study. SETTING: A tertiary referral academic hospital. MAIN OUTCOME MEASUREMENTS: Incidence of complications after ERCP. PATIENTS AND RESULTS: A total of 85 ERCPs among 30 patients with PSC and 70 ERCPs among 45 control patients were reviewed. There was no significant difference in the overall complication rates between patients with and without PSC (11/85 [12.9%] vs 6/70 [8.6%], P = .45). Complications in PSC were more likely to occur after ERCP done to evaluate an acute sign or symptom than in elective cases (7/24 [29.2%] vs 4/61 [6.6%], P = .01). Patients with PSC who had complications had more total and acute ERCPs than did those without complications. There was no significant difference in the rate of complications in diagnostic versus therapeutic ERCPs nor between stent placement and dilation-only therapeutic ERCPs in the PSC population. LIMITATIONS: Retrospective study design and limited power related to the small sample sizes. CONCLUSIONS: Elective ERCP is safe and carries a modest risk in patients with PSC; however, ERCP for acute indications greatly increases the probability of postprocedure complications. The overall complication rate after therapeutic ERCP in patients with PSC is similar to that in patients without PSC.

Genetic variation at the human alpha2B-adrenergic receptor locus: role in blood pressure variation and yohimbine response.

Exaggerated response to alpha2-adrenergic receptor (alpha2-AR) blockade by yohimbine in normotensive subjects is an intermediate phenotype that predicts increased risk for development of hypertension. Here, we assessed the 3 alpha2-AR loci (alpha2A, alpha2B, alpha2C) as candidate genes for their influence on baseline and yohimbine-mediated increase in mean arterial pressure. Because initial results with 173 individuals implicated a possible association of yohimbine response with genetic variation at a site in the alpha2B-AR gene, but not at sites in the other 2 alpha2-AR, we sequenced the alpha2B-AR gene (4.4 kb, including 1.2 kb upstream and 1.9 kb distal to the coding sequence) in those subjects and an additional 81 individuals to search for other alpha2B-AR variants. We identified 25 polymorphisms, of which 14 are previously unreported, and 2 major haplotypes that differ by the presence/absence of a 9-bp in-frame deletion that encodes Glu301 to Glu303. Frequency differences in haplotypes were observed between blacks and whites but did not predict response to yohimbine. Genotyping of 2 additional white cohorts, including 1269 individuals with extremes in blood pressure selected from >50,000 subjects, also failed to reveal an association of the 2 major alpha2B-AR haplotypes with differences in blood pressure. Thus, despite considerable polymorphism in alpha2-AR genes, such variation is not a major determinant of variability in yohimbine response and by inference, in susceptibility to essential hypertension.