A postal questionnaire inquiring about routine sedation and premedication practice for upper gastrointestinal endoscopy was sent to 1048 doctors. Of 665 appropriate returns, 81% were from consultant physicians and surgeons. Most endoscopists (90%) reported using an intravenous benzodiazepine for at least three quarters of endoscopies and 54% of physicians and 69% of surgeons always did so. Midazolam was the intravenous sedative used by a third of ali respondents and 13% also used an additional intravenous agent, usualiy pethidine. Over the previous two years a total of 119 respiratory arrests, 37 cardiac arrests, and 52 deaths were identified. Adverse outcomes were reported more frequently by consultant physicians, by those who 'titrated' the intravenous sedative, and by those who used an additional intravenous agent, but were reported equaliy frequently by endoscopists using midazolam and endoscopists using diazepam. There is an urgent need for a prospective study to identify the circumstances and risk factors associated with adverse outcomes related to endoscopy.
AIMS:The aim of this study was to investigate MlF expression and activity in human sporadic colorectal adenomas and in intestinal adenomas from the Apc mouse model of familial adenomatous polyposis. METHODS: lmmunohistochemistry was performed on archival formalin-fixed, paraffin-embedded human sporadic colorectal adenomas (n=56), and on small and large intestine of Apc mice and wild type littermates. Human MLF protein levels were analysed in fresh paired colorectal adenoma and normal mucosa samples by ELSA (n=16) and by Western blot analysis (n=8). A phydroxyphenylpyruvate (HPP) tautomerase assay was used to measure specific MIF activity in paired fresh tissue (n=20). RESULTS: In human colorectal tissue, immunohistochemistry and Western blot analysis both demonstrated increased MIF protein levels in adenomas compared with paired normal colorectal mucosa. MIF was localised to both epithelial (particularly the apical membrane) and stromal cells in adenomas. The ELISA demonstrated a mean 1.9-fold increase (95% CI 1.1-2.7) in immunoreactive MlF in adenomas compared with paired normal mucosa. The HPP tautomerase assay revealed a mean 1.5-fold increase (95% CI 1.2-1.7) in MIF activity in adenomas. Inmunohistochemical analysis in the Apc mouse intestine revealed a similar pattern of protein localisation in adenomas and histologically normal mucosa, with MIF localisation in dysplastic epithelial cells being prominent. CONCLUSIONS: MIF protein levels are increased in human sporadic colorectal adenomas and in intestinal adenomas from the Apc mouse. The precise role of MIF in epithelial and stromal cell compartments of adenomas during the early stages of intestinal tumorigenesis is currently being investigated.
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