RQ-00201894: A motilin receptor agonist causing long-lasting facilitation of human gastric cholinergically-mediated contractions.

The aim was to characterise RQ-00201894, a novel non-macrolide motilin agonist, using human recombinant receptors and then investigate its ability to facilitate cholinergic activity in human stomach. A reporter gene assay assessed motilin receptor function. Selectivity of action was determined using a panel of different receptors, ion channels, transporters and enzymes. Cholinergically-mediated muscle contractions were evoked by electrical field stimulation (EFS) of human gastric antrum. The results showed that RQ-00201894, motilin and erythromycin acted as full motilin receptor agonists (EC50: 0.20, 0.11, 69 nM, respectively). In this function, RQ-00201894 had >90-fold selectivity of action over its ability to activate the human ghrelin receptor (EC50 19 nM) and greater selectivity over all other receptors/mechanisms tested. In human stomach RQ-00201894 0.1-30 µM concentration-dependently increased EFS-evoked contractions (up to 1209%; pEC50 6.0). At 0.1-10 µM this activity was usually prolonged. At higher concentrations (3-30 µM) RQ-00201894 also caused a short-lasting muscle contraction, temporally disconnected from the increase in EFS-evoked contractions. RQ-00201894 10 µM did not consistently affect submaximal contractions evoked by carbachol. In conclusion, RQ-00201894 potently and selectively activates the motilin receptor and causes long-lasting facilitation of cholinergic activity in human stomach, an activity thought to correlate with an ability to increase gastric emptying.

Sleeve gastrectomy as a bridge to a second bariatric procedure in superobese patients--a single institution experience.

BACKGROUND: The surgical treatment of superobese patients (body mass index ≥50 kg/m(2)) with significant co-morbidities remains a challenge. We evaluated our outcomes after initial laparoscopic sleeve gastrectomy (LSG) in the superobese undergoing staged procedures in the setting of a university hospital in the United Kingdom. METHODS: The data from patients with a body mass index of ≥50 kg/m(2) undergoing LSG as a part of a staged procedure from 2005 to 2008 were extracted from our database. The patient parameters were analyzed, along with the morbidity, length of stay, and weight loss after the initial procedure. RESULTS: A total of 61 patients with a body mass index of ≥50 kg/m(2) (median 60, range 50-81.5) underwent LSG as a part of a staged procedure during the study period. The median age was 46 years (range 24-61.5), and 41 were women. Obesity-related co-morbidities were present in different combinations in 51 patients (83.6%). All the procedures were completed laparoscopically, barring 1. The median hospital stay was 4 days (interquartile range 3-4). Complications occurred in 6 patients (9.8%), and 3 required repeat laparoscopy for complications. No patient died. The median percentage of excess weight loss was 31% at 6 months (interquartile range 26-40) and 39% at 1 year (interquartile range 34-51). Diabetes, obstructive sleep apnea and hypertension had resolved in 90%, 100%, and 61% of the patients, respectively. Of the 61 patients, 41 went on to undergo a second-stage procedure, of whom 1 underwent laparoscopic Roux-en-Y gastric bypass, 5 underwent repeat LSG, and the rest underwent laparoscopic duodenal switch. CONCLUSIONS: LSG is safe and effective for initial weight loss in the superobese undergoing 2-stage procedures.

Clip closure versus endoscopic suturing versus thoracoscopic repair of an iatrogenic esophageal perforation: a randomized, comparative, long-term survival study in a porcine model (with videos).

BACKGROUND: Esophageal full-thickness wall repair is an important but unsolved issue in endoscopy. It is unknown how well endoscopic clip closure (ECC) and endoscopic closure with suturing (ECS) perform compared with the criterion standard of thoracoscopic closure (TC). OBJECTIVE: Comparison of technical success, feasibility, long-term patency, complications, and histological quality of the different closure techniques (ECC, ECS, TC) for esophageal perforations. DESIGN: Comparative animal study. SETTING: Approved animal facility. SUBJECTS: Eighteen pigs. INTERVENTIONS: Eighteen pigs were randomized, 6 each into 3 groups (ECC, ECS, TC). After endoscopic wall incision and mediastinoscopy, closure was performed by using 1 of the 3 techniques. After 8 to 12 weeks, pre-euthanasia endoscopic, necropsy, histological, and morphometric analyses were performed. MAIN OUTCOME MEASUREMENT: Long-term survival and histological quality of the repair. RESULTS: The closure of the esophageal incisions was successful in all pigs. On days 2 and 6, 1 animal died of mediastinitis, 1 in the ECS group because of reflux of gastric contents into the mediastinum before the repair and 1 in the TC group because of leakage of the sutured closure (P = 1.0). No strictures were seen on prenecropsy endoscopy. At necropsy, 1 mediastinal abscess was found in an ECS animal (P = 1.0). Minor complications included periesophageal adhesions and reactive lymph nodes in 3 of 6 (ECC group) and 5 of 6 (TC and ECS groups). Histology showed muscle layer defects up to 12 mm in width and 21 mm in length, with a trend toward smaller defect size of width and length in the ECS group of animals. LIMITATIONS: Animal study of limited size. CONCLUSIONS: Overall, ECS and ECC performed similarly to TC. ECS showed the smallest histological defects in the long-term repair.