Do clinical characteristics predict the presence of small bowel angioectasias on capsule endoscopy?

BACKGROUND AND AIMS: Angioectasias (AVMs) are the most common vascular anomaly of the gastrointestinal (GI) tract, and these lesions are often associated with obscure gastrointestinal bleeding (OGIB). It is unknown if the presence of upper and/or lower gastrointestinal AVMs are predictive of small bowel AVMs. The aims of this study are to define the small bowel segmental distribution of AVMs and to identify the factors predicting the presence of small bowel AVMs among a cohort of patients with a known history of AVMs in the upper and/or lower GI tracts who are undergoing capsule endoscopy (CE) for OGIB. METHODS: We performed a retrospective cohort analysis of 1,125 patients undergoing CE at our institution between 11/1/2001 and 8/31/2007. Inclusion criteria were: (1) complete esophagoduodenoscopy (EGD), CE, and colonoscopy, (2) OGIB indication for CE, and (3) history of ≥ 1 AVM on EGD and/or colonoscopy that was previously treated in the past or deemed not to be a clinically significant source of bleeding. Exclusion criteria were: (1) history of radiation therapy to the GI tract, and (2) presence of a congenital or systemic disease associated with GI AVMs. Data were extracted on: (1) age; (2) gender; (3) presence of diabetes, (4) presence of hypertension, (5) presence of aortic stenosis, (6) history of non-steroidal anti-inflammatory therapy, (7) history of anticoagulant therapy, (8) hemoglobin, platelet, and INR values prior to CE; (9) baseline serum creatinine; and (10) presence and GI tract segmental location of AVMs. Multivariate logistic regression was used to identify independent predictors of small bowel AVMs. RESULTS: 1,125 patients underwent EGD, CE, and colonoscopy. One hundred and fourteen patients had a history of ≥ 1 AVM on EGD and/or colonoscopy and met inclusion and exclusion criteria. The mean age was 69 years, and 63% of patients were women. 37% of patients were found to have ≥ 1 jejunal AVM and 15% were found to have ≥ 1 ileal AVM. In multivariate analysis, age ≥ 65 (OR 2.62, P = 0.05) and the presence of AVMs on EGD (OR 4.61, P = 0.02) were predictive of jejunal AVMs. AVMs on colonoscopy alone were not predictive of jejunal or ileal AVMs. No factors were found to predict the presence of ileal AVMs. CONCLUSIONS: Patients with AVMs on EGD have an increased risk of jejunal AVMs on CE, particularly if they are elderly. Future studies should validate these findings in a prospective cohort.

Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: a mechanism of ineffective host defense.

Helicobacter pylori evades host immune defenses and causes chronic gastritis. Immunity against intestinal pathogens is largely mediated by dendritic cells, yet the role of dendritic cells in acute H. pylori infection is largely unknown. We observed the recruitment of dendritic cells to the gastric mucosa of H. pylori-infected mice. Bone marrow-derived dendritic cells from mice responded to live H. pylori by upregulating the expression of proinflammatory cytokine mRNA (i.e., IL-1alpha, IL-1beta, and IL-6). The supernatant from dendritic cells stimulated with H. pylori for 18 h contained twofold higher levels of IL-12p70 than IL-10 and induced the proliferation of syngeneic splenocytes and type 1 T helper cell cytokine release (IFN-gamma and TNF-alpha). These responses were significantly lower compared with those induced by Acinetobacter lwoffi, another gastritis-causing pathogen more susceptible to host defenses. Analysis of whole H. pylori sonicate revealed the presence of a heat-stable factor secreted from H. pylori that specifically inhibited IL-12 but not IL-10 release from dendritic cells activated by A. lwoffi. Our findings suggest that dendritic cells participate in the host immune response against H. pylori and that their suppression by H. pylori may explain why infected hosts fail to prevent bacterial colonization.

The use of wireless capsule endoscopy in clinical diagnostic gastroenterology.

This profile describes a new wireless video endoscopy device designed to image previously inaccessible areas of the gastrointestinal tract with unprecedented precision and clarity. This PillCam technology involves a disposable, ingestible camera that transmits more than 50,000 digital images of the small bowel to personal computer software. The wireless capsule endoscopy technology supplements and is rapidly replacing standard small bowel imaging techniques, and its use has revolutionized conventional ideas about the small bowel's role in many conditions such as Crohn's disease and occult blood loss. In addition to the small bowel device, an esophageal adaptation was released in January 2005. This capsule technology anticipates exponential growth in both diagnostic and possible therapeutic dimensions in the future.

Signaling pathways involved in IL-8-dependent activation of adhesion through Mac-1.

In human neutrophils, IL-8 induces chemotaxis, the respiratory burst, and granule release, and enhances cellular adhesion, a beta(2) integrin-dependent event. IL-8 stimulates neutrophil adhesion to purified fibrinogen in a Mac-1-dependent manner. Mitogen-activated protein kinase (MAPK) activation was detected in human neutrophil lysates after treatment with IL-8 and PMA, but not the activating mAb CBR LFA 1/2. IL-8-stimulated neutrophil adhesion to fibrinogen was blocked 50% by the MAPK/extracellular signal-related kinase-activating enzyme inhibitor PD098059. Adhesion was blocked approximately 75% by inhibition of the phosphatidylinositol-3 kinase (PI3K) pathway with LY294002, supporting that activation of both MAPK and PI3K may play a role in IL-8-dependent inside-out signals that activate Mac-1. Activation of MAPK was inhibited in IL-8-stimulated cells in the presence of PI3K inhibitors LY294002 or wortmannin, supporting a model in which PI3K is upstream of MAPK. IL-8-stimulated neutrophil adhesion was inhibited 50% by bisindolylmaleimide-I, implicating protein kinase C (PKC) in the intracellular signaling from the IL-8R to Mac-1. A 74-kDa molecular mass species was detected by an activation-specific Ab to PKC when cells were stimulated with PMA or IL-8, but not a beta(2)-activating Ab. Inhibition of either MAPK or PKC resulted in partial inhibition of IL-8-stimulated polymorphonuclear neutrophil adhesion, and treatment with both inhibitors simultaneously completely abolished IL-8-stimulated adhesion to ligand. Inhibition of PI3K blocked MAPK activation, but not PKC activation, suggesting a branch point that precedes PI3K activation. These data suggest that both MAPK and PKC are activated in response to IL-8 stimulation, and that these may represent independent pathways for beta(2) integrin activation in neutrophils.