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John Dent

Publications and source records attributed to John Dent.

5 recordsLinked to original sources
PubMed2003

Radiofrequency energy delivery to the gastric cardia inhibits triggering of transient lower esophageal sphincter relaxation and gastroesophageal reflux in dogs.

BACKGROUND: Delivery of radiofrequency energy to the lower esophageal sphincter and gastric cardia is a new endoluminal technique proposed for the treatment of reflux disease. The mechanisms by which it achieves its effects are unclear. The study assessed the effect of radiofrequency energy delivery to the gastric cardia on the triggering of transient lower esophageal sphincter relaxations and gastroesophageal reflux in dogs. METHODS: In 13 dogs, esophageal motility and pH were measured for 1 hour after a standard liquid meal and air infusion, as well as before and 3 months after radiofrequency energy treatment. At 7 months, histologic evaluation of the gastroesophageal junction was performed. RESULTS: Radiofrequency energy delivery reduced the frequency of transient lower esophageal sphincter relaxations from 4.0 (3.0-6.75) (median [interquartile range]) per hour to 3.0 (2.0-3.0) per hour (p < 0.05). This was accompanied by a significant reduction in acid reflux episodes and esophageal acid exposure. Basal lower esophageal sphincter pressure and lower esophageal sphincter relaxation during swallowing were unchanged. There was a 63% increase in wall thickness at the gastric cardia compared with that in 2 control dogs, but no gross or histopathologic abnormalities of the esophageal or gastric mucosa. CONCLUSION: Radiofrequency energy delivery to the gastric cardia in dogs inhibits the triggering of transient lower esophageal sphincter relaxations and thereby reduces gastroesophageal reflux.

Animals↗
PubMed2002

Oesophageal disorders: future developments.

Elicitation of the characteristic symptom patterns remains the primary approach to the diagnosis of gastro-oesophageal reflux disease, and this may be enhanced by developments in the use of high-resolution endoscopy and oesophageal biopsy. For future therapy, proton pump inhibitors and anti-reflux surgery may compete with reversible acid pump blockers, reflux inhibitor drugs and diverse luminally delivered physical anti-reflux therapies. Short-segment Barrett's oesophagus is known to be highly prevalent, but its impact on the risk of adenocarcinoma remains poorly defined. Biomarkers for Barrett's oesophagus have been proposed to aid in the stratification of cancer risk, and cytology may assume more importance in the future. Endoscopic surveillance for Barrett's oesophagus is widely practised, but more data are needed to demonstrate cost-effectiveness and a positive impact on mortality. Animal and limited human studies suggest that chemoprevention may become an important strategy in reducing the risk of adenocarcinoma. The ablation of Barrett's epithelium results in a reversal of Barrett's epithelium, albeit with an uncertain long-term outcome.

Adenocarcinoma↗
PubMed2002

Shed human enterocytes as a tool for the study of expression and function of intestinal drug-metabolizing enzymes and transporters.

OBJECTIVES: Intestinal metabolism and transport are now recognized as protective barriers against orally ingested xenobiotics, including drugs. However, in vitro studies of the expression and function of intestinal proteins are hampered by the limited availability of human intestinal tissues. Because enterocytes are constantly shed in large numbers into the gut lumen, this study investigated whether these cells could be collected with a multilumen perfusion catheter and whether they are functionally active. METHODS: In healthy volunteers, a 20-cm isolated jejunal segment was generated with the perfusion catheter by inflating 2 balloons with air. Shed cells were characterized by fluorescence-activated cell sorting analysis for leukocyte-specific CD45 and enterocyte-specific villin, as well as for apoptosis. Homogenates of the cells were used for reverse transcriptase polymerase chain reaction and Western blotting. Cytochrome P450 enzyme activity was determined with the calcium channel blocker verapamil as a substrate. RESULTS: On average, 4.83 mg protein and 56.23 million cells were collected from a 20-cm segment during 2 hours. A total of 84.2% of the cells were positive for enterocyte-specific villin, and only 1.6% of the collected cells were positive for CD45. The majority of cells (65.3%) were not in early or late apoptosis or necrosis. In all volunteers, drug-metabolizing enzymes (such as members of the cytochrome P450 family) could be detected as both messenger ribonucleic acid and proteins. Consistent with expression data, formation of verapamil metabolites catalyzed by CYP3A4 and CYP2C was shown. CONCLUSIONS: The majority of shed human enterocytes collected with a multilumen perfusion catheter were still functionally active and not apoptotic. Harvesting of spontaneously shed enterocytes provides a new tool for studies on expression and function of intestinal proteins.

Adult↗