Hyperpolarization-activated cyclic nucleotide-gated cation channel subtypes differentially modulate the excitability of murine small intestinal afferents

AIM： To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation （HCN） channels in regu- lating the excitability of vagal and spinal gut afferents. METHODS： The mechanosensory response of mesen- teric afferent activity was measured in an ex vivo murine jejunum preparation. HCN channel activity was recorded through voltage and current clamp in acutely dissoci- ated dorsal root ganglia （DRG） and nodose ganglia （NG） neurons retrogradely labeled from the small intestine through injection of a fluorescent marker （DiI）. The isoforms of HCN channels expressed in DRG and NG neurons were examined by immunohistochemistry. RESULTS： Ramp distension of the small intestine evok- ed biphasic increases in the afferent nerve activity, re- flecting the activation of low- and high-threshold fibers.HCN blocker CsCl （5 mmol/L） preferentially inhibited the responses of low-threshold fibers to distension and showed no significant effects on the high-threshold re- sponses. The effect of CsCI was mimicked by the more selective HCN blocker ZD7288 （10 ~mol/L）. In 71.4% of DiI labeled DRG neurons （/7 = 20） and 90.9% of DiI labeled NG neurons （n = 10）, an inward current （Ih current） was evoked by hyperpolarization pulses which was fully eliminated by extracellular CsCI. In neurons expressing Ih current, a typical ＂sag＂ was observed upon injection of hyperpolarizing current pulses in cur- rent-clamp recordings. CsCI abolished the sag entirely. In some DiI labeled DRG neurons, the Ih current was potentiated by 8-Br-cAMP, which had no effect on the Ih current of DiI labeled NG neurons. Immunohistochem- istry revealed differential expression of HCN isoforms in vagal and spinal afferents, and HCN2 and HCN3 seemed to be the dominant isoform in DRG and NG, respec- tively.CONCLUSION： HCNs differentially regulate the excit- ability of vagal and spinal afferent of murine small in- testine.

Managementofearlyasymptomaticgastrointestinalstromaltumorsofthe stomach

Gastrointestinal stromal tumors(GIST) are the most common mesenchymal tumors of the digestive tract. Approximately two thirds of clinically manifest tumors occur in the stomach, nearly one third in the small bowel, and the rest in the colorectal region with a few cas-es in the esophagus. GIST originate within the smooth muscle layer in the wall of the tubular gastrointestinal tract and grow mostly toward the serosa, far less often toward the mucosa. In the latter case, ulceration may develop and can cause gastrointestinal bleeding as the cardinal symptom. However, most GIST of the stomach are asymptomatic. They are increasingly detected incidentally as small intramural or submucosal tumors during endoscopy and particularly during endoscopic ultra-sound. Epidemiological and molecular genetic findings suggest that early asymptomatic GIST of the stomach(< 1 cm) show self-limiting tumorigenesis. Thus, early(< 1 cm) asymptomatic gastric GIST(synonym: micro-GIST) are found in 20%-30% of the elderly. The mostlyelderly people with early gastric GIST have an excellent GIST-specific prognosis. Patients with early GIST of the stomach can therefore be managed by endoscopic sur-veillance.

Posterior lingual lidocaine: A novel method to improve tolerance in upper gastrointestinal endoscopy

AIM: To evaluate the effect of posterior lingual lidocaine swab on patient tolerance to esophagogastro-duodenoscopy, the ease of performance of the procedure, and to determine if such use will reduce the need for intravenous sedation. METHODS: Eighty patients undergoing diagnostic esophagogastroduodenoscopy in a tertiary care medical center were randomized to either lidocaine swab or spray. Intravenous meperidine and midazolam were given as needed during the procedure. RESULTS: Patients in the lidocaine swab group (SWG) tolerated the procedure better than those in the spray group (SPG) with a median tolerability score of 2 (1, 4) compared to 4 (2, 5) (P < 0.01). The endoscopists encountered less diffi culty performing the proceduresin the SWG with lower median difficulty scores of 1 (1, 5) compared to 4 (1, 5) in the SPG (P < 0.01). In addition, the need for intravenous sedation was also lower in the SWG compared to the SPG with fewer patients requiring intravenous sedation (13/40 patients vs 38/40 patients, respectively, P < 0.01). The patients in the SWG were more satisfi ed with the mode of local anesthesia they received as compared to the SPG. In addition, the endoscopists were happier with the use of lidocaine swab. CONCLUSION: The use of a posterior lingual lidocaine swab in esophagogastroduodenoscopy improves patient comfort and tolerance and endoscopist satisfaction and decreases the need for intravenous sedation.