Effect of Proton Pump Inhibitor Therapy on NOX5, mPGES1 and iNOS expression in Barrett's Esophagus.

Acid reflux may contribute to the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA). However, it is not clear whether the molecular changes present in BE patients are reversible after proton pump inhibitor (PPI) treatment. In this study we examined whether PPI treatment affects NOX5, microsomal prostaglandin E synthase (mPGES)-1 and inducible nitric oxide synthase (iNOS) expression. We found that NADPH oxidase 5 (NOX5), mPGES-1 and iNOS were significantly increased in BE mucosa. One-month PPI treatment significantly decreased NOX5, mPGES1 and iNOS. In BAR-T cells, NOX5 mRNA and p16 promoter methylation increased after pulsed acid treatment in a time-dependent manner. Four or eight-week-acid induced increase in NOX5 mRNA, NOX5 protein and p16 methylation may be reversible. Twelve-week acid treatment also significantly increased NOX5, mPGES1 and iNOS mRNA expression. However, twelve-week-acid-induced changes only partially restored or did not recover at all after the cells were cultured at pH 7.2 for 8 weeks. We conclude that NOX5, mPGES1 and iNOS may be reversible after PPI treatment. Short-term acid-induced increase in NOX5 expression and p16 methylation might be reversible, whereas long-term acid-induced changes only partially recovered 8 weeks after removal of acid treatment.

Is there physician bias against eliciting affective qualities of pain?

GOALS: The purpose of this study is to determine the weight given to each of 3 pain dimensions by physicians who assess patients' pain experiences. BACKGROUND: Pain is a subjective experience that has profound impact on the quality of life. The 101-Multidimensional Affect and Pain Survey (101-MAPS) is currently the only available instrument that takes into account all 3 validated dimensions of pain by classifying 101 items into "superclusters" of sensory pain, suffering, and well-being. STUDY: Fourteen gastroenterologists, 11 internists, and 11 medicine residents from 2 teaching hospitals rated the items on the 101-MAPS based on their perception of the items' relevance to pain in gastrointestinal diseases, on a scale of 0 (least relevant) to 5 (most relevant). RESULTS: Of the 101 items in the MAPS rated by gastroenterologists, 25 items received a median rating of 4 or above. Of these, 23 were selected from the 57 items in the sensory pain supercluster (40%) and only 1 item each from the 26 in the suffering (3.8%), and the 18 in the well-being (5.5%) dimensions. These proportions were significantly lower for the suffering (P<0.01) and well-being (P<0.05) superclusters than for the sensory pain dimension. CONCLUSIONS: These findings suggest a bias among physicians toward sensory and against affective qualities when eliciting patients' pain experiences. The results also suggest that this bias is found as early as residency training and persists among specialists.

Cyclosporine and infliximab as rescue therapy for each other in patients with steroid-refractory ulcerative colitis.

BACKGROUND & AIMS: In patients with severe corticosteroid-refractory ulcerative colitis, cyclosporine or infliximab may be added in an effort to induce remission. If the patient then fails either of these drugs, it is unknown whether success can be achieved by using the other agent. The aim of this study was to assess outcomes of using cyclosporine after failure of infliximab, and vice versa. METHODS: We retrospectively reviewed the charts of 19 patients with corticosteroid-refractory ulcerative colitis who received either infliximab after failed cyclosporine or cyclosporine after failed infliximab. Acute salvage therapy was defined as having received the alternate drug within 4 weeks of discontinuing the first agent. RESULTS: Ten patients received infliximab after failing cyclosporine; 9 patients received cyclosporine after failing infliximab. Four patients (40%) in the infliximab-salvage group achieved remission, as did 3 (33%) in the cyclosporine-salvage group. Remission lasted a mean of 10.4 months (range, 4.4-17.03 mo) and 28.5 months (range, 5.0-41.5 mo), respectively. Severe adverse events included one patient who developed sepsis and died after receiving infliximab salvage. One patient who received cyclosporine salvage developed herpetic esophagitis, and another patient who received cyclosporine salvage developed pancreatitis and bacteremia. CONCLUSIONS: In patients with severe corticosteroid-refractory ulcerative colitis who fail treatment with either cyclosporine or infliximab, remission rates using acute salvage therapy by crossing over to the other drug occur in approximately one third of patients and have limited duration. Serious adverse events occurred in 16%, including 1 death, suggesting that the risks of acute salvage therapy may outweigh the benefits.