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Stephen B Hanauer

Publications and source records attributed to Stephen B Hanauer.

At least 37 records · Page 2Linked to original sources
PubMed2006

Phenotype-stratified genetic linkage study demonstrates that IBD2 is an extensive ulcerative colitis locus.

OBJECTIVES: The complete elucidation of genetic variants that contribute to inflammatory bowel disease (IBD) will likely include variants that increase risk to both Crohn's disease and ulcerative colitis as well as variants that increase risk for particular phenotypic subsets. The purpose of this study was to assess phenotypic subsets that contribute to the major IBD susceptibility loci. METHODS: This linkage study encompassed 904 affected relative pairs, representing the largest combined phenotyped cohort to date, and allowing for meaningful subset analyses. Genetic linkage data were stratified by disease location and age at diagnosis. RESULTS: We establish that some loci, notably the IBD3 and chromosome 3q linkage regions demonstrate contributions from both small intestine and colon cohorts, whereas others, notably the IBD1 (NOD2/CARD15) and IBD2 regions increase risk for small intestine or colon inflammation, respectively. The strongest linkage evidence in this study was for the subset of extensive ulcerative colitis in the region of IBD2 (lod 3.27; p < 0.001). Evidence for linkage in the region of NOD2/CARD15 (IBD1) was stronger for the subset of Crohn's patients with ileal disease (lod 2.56; p= 0.035) compared to the overall Crohn's group, consistent with previous findings that NOD2/CARD15 variants are associated with ileal disease. CONCLUSIONS: Analyses incorporating disease location in IBD increase the power and enhance the accuracy of genomic localization. Our data provide strong evidence that extensive ulcerative colitis represents a pathophysiologic subset of IBD.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Factors associated with the development of intestinal strictures or obstructions in patients with Crohn's disease.

OBJECTIVE: Theoretical concern exists that rapid luminal healing in Crohn's disease (CD) with therapies like infliximab increases the risk of intestinal stenosis, stricture, or obstruction (SSOs). METHODS: Data were analyzed from the ongoing observational TREAT (the Crohn's Therapy, Resource, Evaluation, and Assessment Tool) Registry and ACCENT I (A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-Term Treatment Regimen) study. Investigators reported SSOs as adverse events or serious adverse events. RESULTS: In TREAT, SSOs occurred at a significantly higher rate in patients treated with infliximab compared with patients who received other treatments only (1.95 events/100 patient-years vs 0.99 events/100 patient-years; p < 0.001). Using multivariable analyses, however, infliximab therapy was not associated with SSO development. CD severity at the time of event onset (hazard ratio (HR) = 2.35, 95% confidence internal (CI) 1.35-4.09); CD duration (HR = 1.02, 95% CI 1.00-1.04); ileal disease (HR = 1.56, 95% CI 1.04-2.36); and new corticosteroid use (HR = 2.85, 95% CI 1.23-6.57) were associated with SSOs. In ACCENT I, no increase in SSOs was reported in patients who received infliximab maintenance therapy compared with those who received episodic therapy, despite higher median cumulative infliximab exposure. Additionally, there was no increase in SSO development with rapid mucosal healing (healing at week 10). CONCLUSIONS: Although unadjusted analyses suggested that patients who received infliximab were twice as likely to develop SSOs, multivariable analysis adjusting for other factors demonstrated that only disease duration, disease severity, ileal disease, and new corticosteroid use were significantly associated with SSO development.

Adolescent↗
PubMed2006

Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohort.

OBJECTIVES: Inflammatory bowel disease (IBD), comprising primarily of Crohn's disease (CD) and ulcerative colitis (UC), is increasingly prevalent in racial and ethnic minorities. This study was undertaken to characterize racial differences in disease phenotype in a predominantly adult population. METHODS: Phenotype data on 830 non-Hispanic white, 127 non-Hispanic African American, and 169 Hispanic IBD patients, recruited from six academic centers, were abstracted from medical records and compiled in the NIDDK-IBD Genetics Consortium repository. We characterized racial differences in family history, disease location and behavior, surgical history, and extraintestinal manifestations (EIMs) using standardized definitions. RESULTS: African American CD patients were more likely than whites to develop esophagogastroduodenal CD (OR = 2.8; 95% CI: 1.4-5.5), colorectal disease (OR = 1.9; 95% CI: 1.1-3.4), perianal disease (OR = 1.7; 95% CI: 1.03-2.8), but less likely to have ileal involvement (OR = 0.55; 95% CI: 0.32-0.96). They were also at higher risk for uveitis (OR = 5.5; 95% CI: 2.3-13.0) and sacroiliitis (OR = 4.0; 95% CI: 1.55-10.1). Hispanics had higher prevalence of perianal CD (OR = 2.9; 95% CI: 1.8-4.6) and erythema nodosum (3.3; 95% CI: 1.7-6.4). Among UC patients, Hispanics had more proximal disease extent. Both African American and Hispanic CD patients, but not UC patients, had lower prevalences of family history of IBD than their white counterparts. CONCLUSIONS: There are racial differences in IBD family history, disease location, and EIMs that may reflect underlying genetic variations and have important implications for diagnosis and management of disease. These findings underscore the need for further studies in minority populations.

Adult↗
PubMed2006

Best of DDW 2006.

Highlights from the 2006 Digestive Disease Week May 20-25, 2006, Los Angeles, CA. In this meeting review, many of our editorial board members report on Digestive Disease Week 2006. They highlight the most noteworthy presentations in their respective areas of expertise, including the latest treatments, technologies, and diagnostic advances in ulcerative colitis, Crohn's disease, Helicobacter pylori infection, gastroesophageal reflux disease, irritable bowel syndrome, colorectal cancer, pancreatic and biliary disease, and liver disease.

Digestive System Diseases↗
PubMed2005

Infliximab for induction and maintenance therapy for ulcerative colitis.

BACKGROUND: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor alpha, is an established treatment for Crohn's disease but not ulcerative colitis. METHODS: Two randomized, double-blind, placebo-controlled studies--the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively)--evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. RESULTS: In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P< or =0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons). CONCLUSIONS: Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.)

Adult↗
PubMed2005

Natalizumab induction and maintenance therapy for Crohn's disease.

BACKGROUND: Natalizumab, a humanized monoclonal antibody against alpha4 integrin, inhibits leukocyte adhesion and migration into inflamed tissue. METHODS: We conducted two controlled trials to evaluate natalizumab as induction and maintenance therapy in patients with active Crohn's disease. In the first trial, 905 patients were randomly assigned to receive 300 mg of natalizumab or placebo at weeks 0, 4, and 8. The primary outcome was response, defined by a decrease in the Crohn's Disease Activity Index (CDAI) score of at least 70 points, at week 10. In the second trial, 339 patients who had a response to natalizumab in the first trial were randomly reassigned to receive 300 mg of natalizumab or placebo every four weeks through week 56. The primary outcome was a sustained response through week 36. A secondary outcome in both trials was disease remission (a CDAI score of less than 150). RESULTS: In the first trial, the natalizumab and placebo groups had similar rates of response (56 percent and 49 percent, respectively; P=0.05) and remission (37 percent and 30 percent, respectively; P=0.12) at 10 weeks. Continuing natalizumab in the second trial resulted in higher rates of sustained response (61 percent vs. 28 percent, P<0.001) and remission (44 percent vs. 26 percent, P=0.003) through week 36 than did switching to placebo. Serious adverse events occurred in 7 percent of each group in the first trial and in 10 percent of the placebo group and 8 percent of the natalizumab group in the second trial. In an open-label extension study, a patient treated with natalizumab died from progressive multifocal leukoencephalopathy, associated with the JC virus, a human polyomavirus. CONCLUSIONS: Induction therapy with natalizumab for Crohn's disease resulted in small, nonsignificant improvements in response and remission rates. Patients who had a response had significantly increased rates of sustained response and remission if natalizumab was continued every four weeks. The benefit of natalizumab will need to be weighed against the risk of serious adverse events, including progressive multifocal leukoencephalopathy. (ClinicalTrials.gov numbers, NCT00032786 and NCT00032799.)

Adult↗
PubMed2005

Superior mesenteric vein thrombosis after colectomy in a patient with Crohn's disease.

BACKGROUND: An 18-year-old woman with a history of Crohn's disease presented in January 2004 with severe epigastric pain, nausea and vomiting of 4 hours' duration. The patient was diagnosed with inflammatory bowel disease, thought to be consistent with ulcerative colitis, in March 2003, but had no medical history up until this point. Initial treatment with mesalamine was unsuccessful and she subsequently presented with medically resistant fulminant colitis and required an urgent colectomy in June 2003. Her immediate postoperative course was uneventful and she was discharged on tapering doses of prednisone. In August 2003, an ileoscopy revealed inflamed, mildly ulcerated mucosa, and biopsies were consistent with Crohn's disease. Azathioprine was added to the treatment regimen and the patient tapered off prednisone. At this stage the patient continued to do well clinically up until presentation. INVESTIGATIONS: Small bowel series, abdominal CT scan, abdominal ultrasound, exploratory laparotomy. DIAGNOSIS: Acute mesenteric ischemia secondary to superior mesenteric vein thrombosis. MANAGEMENT: Resection of necrotic bowel, antibiotics and systemic anticoagulation.

Adolescent↗
PubMed2005

Mechanisms of disease: vitamin D and inflammatory bowel disease.

Until recently, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))-the active form of vitamin D-was thought to function primarily as a regulator of calcium and phosphate metabolism. More diverse functionality was indicated by the discovery of the vitamin D receptor in tissues that are not involved in calcium and phosphate homeostasis. Detection of the vitamin D receptor in monocytes and activated T cells has sparked interest in the immunomodulatory properties of vitamin D. Here, we review the role of vitamin D in regulation of the immune system, and evidence for its involvement in the pathogenesis of inflammatory bowel disease.

Animals↗