Lubiprostone neither decreases gastric and small-bowel transit time nor improves visualization of small bowel for capsule endoscopy: a double-blind, placebo-controlled study.

BACKGROUND: Lubiprostone, a selective activator of type 2 chloride channels, is approved for treatment of chronic idiopathic constipation and recently constipation-predominant irritable bowel syndrome. It has been suggested that lubiprostone has a prokinetic effect. OBJECTIVE: This investigation was designed to evaluate lubiprostone as a preparation and propulsive agent for small-bowel capsule endoscopy. The PillCam Small Bowel capsule endoscopy system with the PillCam SB1 capsule and Rapid 5 software platform were used. DESIGN: The study was designed as a double-blind, placebo-controlled trial. PATIENTS: Forty healthy adults. MAIN OUTCOME MEASURES: Gastric transit time (GTT), small-bowel transit time (SBTT), and adequacy of small-bowel cleansing preparation. INTERVENTIONS: The study subjects received 24 mug lubiprostone or placebo 30 minutes before PillCam capsule ingestion. METHODS: Capsule endoscopy studies were read by 2 independent investigators unaware of the study medication received, and differences in interpretation were resolved by consensus. Anatomical landmarks were identified, and GTT and SBTT were calculated. Overall preparation quality assessment of the proximal, mid, and distal small bowel was determined by using a 4-step scale. The percentage of visualized bowel was determined by review of 10-minute video segments at 1-hour intervals after the capsule passed through the pylorus. RESULTS: In the lubiprostone group (n = 20), 2 subjects did not pass the capsule through the pylorus in the 8-hour battery life of the capsule. An additional 3 capsules did not pass into the colon. In the placebo group (n = 20), all capsules passed into the small bowel, but 1 did not pass into the colon. The subjects in whom the capsule did not pass into the small bowel were excluded from the small-bowel analysis. In the subjects in whom the capsule did reach the colon, the SBTT could not be calculated and they were excluded from SBTT analysis. The mean GTT in the lubiprostone group was 126 minutes and 43 minutes in the placebo group (P = .0095). The mean SBTT in the lubiprostone group was 188 minutes and 219 minutes in the placebo group (P = .130). The overall preparation assessment of the small bowel was not statistically significant between the 2 groups in the proximal, mid, or distal small bowel (proximal, P = .119; mid, P = .118; distal, P = .121). There was no significant difference in lubiprostone compared with placebo in the percentage of visualized small bowel. LIMITATIONS: Some capsules did not leave the stomach or reach the cecum. CONCLUSION: Lubiprostone produced a significant increase in GTT but did not result in a significant decrease in SBTT compared with placebo. The administration of lubiprostone before capsule ingestion did not result in improved overall preparation of the small bowel for capsule endoscopy or increase the percentage of visualized small bowel. (The trial was registered at www.clinicaltrials.gov, identifier NCT00746395.).

Boerhaave syndrome presenting as massive hemothorax.

Boerhaave syndrome is a rare entity which classically presents with perforation and mediastinal sepsis. The patients' outcome is directly related to the length of time required to diagnose and surgically address the syndrome. Atypical presentations can contribute to a delay in recognizing the phenomenon, which portends poorly. The case of a man with postemetic esophageal perforation presenting with a massive left hemothorax is presented. To the authors' knowledge, this is the only case of this type to be described in the literature.

Modulation of protein kinase C (PKC)-mediated contraction and the possible role of PKC epsilon in rat mesenteric arteries.

he involvement of protein kinase C (PKC) in isometric tension development of rat mesenteric arteries was investigated. Non-selective inhibition of PKC and selective inhibition of the epsilon isoform were performed using the PKC inhibitor, chelerythrine, and non-viral gene-transfer of a kinase inactive mutant of PKCepsilon (PKCepsilon-KN), respectively. Chelerythrine (2.5 or 5.0 microM) significantly and equally attenuated phenylephrine-induced but not potassium-induced contractions. Higher concentrations of chelerythrine (10 microM) caused the vessels to lose responsiveness to both phenylephrine and potassium chloride. Transfection of blood vessels with epsilon-KN also resulted in significant attenuation of contractile responses to phenylephrine. Potassium chloride-induced responses were not altered in transfected arteries. In a separate group of vessels, the relationship between [Ca2+]i and isometric tension was evaluated. These studies suggested that calcium sensitivity of the contractile apparatus was decreased in vessels when PKC-epsilon activity was compromised. The results of the study suggest that PKC-epsilon can modulate phenylephrine-induced contraction in mesenteric arteries via calcium-independent pathways.