[Show abstract][Hide abstract] ABSTRACT: Little is known about the role of muscularis mucosa at the gastroesophageal junction (GEJ).
To evaluate the movement of the mucosa/muscularis-mucosa/submucosa (MMS) at the GEJ in normal subjects and in patients with gastroesophageal reflux disease (GERD).
Gastroesophageal junctions of 20 non-GERD subjects and 10 patients with GERD were evaluated during 5 mL swallows using two methods: in high-resolution endoluminal ultrasound and manometry, the change in the GEJ luminal pressures and cross-sectional area of esophageal wall layers were measured; in abdominal ultrasound, the MMS movement at the GEJ was analyzed.
Endoluminal ultrasound: In the non-GERD subjects, the gastric MMS moved rostrally into the distal esophagus at 2.17 s after the bolus first reached the GEJ. In GERD patients, the gastric MMS did not move rostrally into the distal esophagus. The maximum change in cross-sectional area of gastroesophageal MMS in non-GERD subjects and in GERD patients was 289 % and 183 %, respectively. Abdominal ultrasound: In non-GERD subjects, the gastric MMS starts to move rostrally significantly earlier and to a greater distance than muscularis propria (MP) after the initiation of the swallow (1.75 vs. 3.00 s) and (13.97 vs. 8.91 mm). In GERD patients, there is no significant difference in the movement of gastric MMS compared to MP (6.74 vs. 6.09 mm). The independent movement of the gastric MMS in GERD subjects was significantly less than in non-GERD subjects.
In non-GERD subjects, the gastric MMS moves rostrally into the distal esophagus during deglutitive inhibition and forms a barrier. This movement of the MMS is defective in patients with GERD.
[Show abstract][Hide abstract] ABSTRACT: To explore whether patients with a defective ileocecal valve (ICV)/cecal distension reflex have small intestinal bacterial overgrowth.
Using a colonoscope, under conscious sedation, the ICV was intubated and the colonoscope was placed within the terminal ileum (TI). A manometry catheter with 4 pressure channels, spaced 1 cm apart, was passed through the biopsy channel of the colonoscope into the TI. The colonoscope was slowly withdrawn from the TI while the manometry catheter was advanced. The catheter was placed across the ICV so that at least one pressure port was within the TI, ICV and the cecum respectively. Pressures were continuously measured during air insufflation into the cecum, under direct endoscopic visualization, in 19 volunteers. Air was insufflated to a maximum of 40 mmHg to prevent barotrauma. All subjects underwent lactulose breath testing one month after the colonoscopy. The results of the breath tests were compared with the results of the pressures within the ICV during air insufflation.
Nineteen subjects underwent colonoscopy with measurements of the ICV pressures after intubation of the ICV with a colonoscope. Initial baseline readings showed no statistical difference in the pressures of the TI and ICV, between subjects with positive lactulose breath tests and normal lactulose breath tests. The average peak ICV pressure during air insufflation into the cecum in subjects with normal lactulose breath tests was significantly higher than cecal pressures during air insufflation (49.33 ± 7.99 mmHg vs 16.40 ± 2.14 mmHg, P = 0.0011). The average percentage difference of the area under the pressure curve of the ICV from the cecum during air insufflations in subjects with normal lactulose breath tests was significantly higher (280.72% ± 43.29% vs 100% ± 0%, P = 0.0006). The average peak ICV pressure during air insufflation into the cecum in subjects with positive lactulose breath tests was not significantly different than cecal pressures during air insufflation 21.23 ± 3.52 mmHg vs 16.10 ± 3.39 mmHg. The average percentage difference of the area under the pressure curve of the ICV from the cecum during air insufflation was not significantly different 101.08% ± 7.96% vs 100% ± 0%. The total symptom score for subjects with normal lactulose breath tests and subjects with positive lactulose breath tests was not statistically different (13.30 ± 4.09 vs 24.14 ± 6.58). The ICV peak pressures during air insufflations were significantly higher in subjects with normal lactulose breath tests than in subjects with positive lactulose breath tests (P = 0.005). The average percent difference of the area under the pressure curve in the ICV from cecum was significantly higher in subjects with normal lactulose breath tests than in subjects with positive lactulose breath tests (P = 0.0012). Individuals with positive lactulose breath tests demonstrated symptom scores which were significantly higher for the following symptoms: not able to finish normal sized meal, feeling excessively full after meals, loss of appetite and bloating.
Compared to normal, subjects with a positive lactulose breath test have a defective ICV cecal distension reflex. These subjects also more commonly have higher symptom scores.
World Journal of Gastroenterology 12/2012; 18(46):6801-8. DOI:10.3748/wjg.v18.i46.6801 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the angle between the circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) fibers in the distal esophagus.
In order to identify possible mechanisms for greater shortening in the distal compared to proximal esophagus during peristalsis, the angles between the LSM and CSM layers were measured in 9 cadavers. The outer longitudinal layer of the muscularis propria was exposed after stripping the outer serosa. The inner circular layer of the muscularis propria was then revealed after dissection of the esophageal mucosa and the underlying muscularis mucosa. Photographs of each specimen were taken with half of the open esophagus folded back showing both the outer longitudinal and inner circular muscle layers. Angles were measured every one cm for 10 cm proximal to the squamocolumnar junction (SCJ) by two independent investigators. Two human esophagi were obtained from organ transplant donors and the angles between the circular and longitudinal smooth muscle layers were measured using micro-computed tomography (micro CT) and Image J software.
All data are presented as mean ± SE. The CSM to LSM angle at the SCJ and 1 cm proximal to SCJ on the autopsy specimens was 69.3 ± 4.62 degrees vs 74.9 ± 3.09 degrees, P = 0.32. The CSM to LSM angle at SCJ were statistically significantly lower than at 2, 3, 4 and 5 cm proximal to the SCJ, 69.3 ± 4.62 degrees vs 82.58 ± 1.34 degrees, 84.04 ± 1.64 degrees, 84.87 ± 1.04 degrees and 83.72 ± 1.42 degrees, P = 0.013, P = 0.008, P = 0.004, P = 0.009 respectively. The CSM to LSM angle at SCJ was also statistically significantly lower than the angles at 6, 7 and 8 cm proximal to the SCJ, 69.3 ± 4.62 degrees vs 80.18 ± 2.09 degrees, 81.81 ± 1.75 degrees and 80.96 ± 2.04 degrees, P = 0.05, P = 0.02, P = 0.03 respectively. The CSM to LSM angle at 1 cm proximal to SCJ was statistically significantly lower than at 3, 4 and 5 cm proximal to the SCJ, 74.94 ± 3.09 degrees vs 84.04 ± 1.64 degrees, 84.87 ± 1.04 degrees and 83.72 ± 1.42 degrees, P = 0.019, P = 0.008, P = 0.02 respectively. At 10 cm above SCJ the angle was 80.06 ± 2.13 degrees which is close to being perpendicular but less than 90 degrees. The CSM to LSM angles measured on virtual dissection of the esophagus and the stomach on micro CT at the SCJ and 1 cm proximal to the SCJ were 48.39 ± 0.72 degrees and 50.81 ± 1.59 degrees. Rather than the angle of the CSM and LSM being perpendicular in the esophagus we found an acute angulation between these two muscle groups throughout the lower 10 cm of the esophagus.
The oblique angulation of the CSM may contribute to the significantly greater shortening of distal esophagus when compared to the mid and proximal esophagus during peristalsis.
World Journal of Gastroenterology 08/2012; 18(32):4317-22. DOI:10.3748/wjg.v18.i32.4317 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The following discussion of the esophagogastric junctions includes commentaries on the three component structures of the sphincteric segment between the stomach and the esophagus; the pressure contributions from the three sphincteric components in normal subjects and in gastroesophageal reflux (GERD) patients; the mechanism of action of endoscopic plication to determine the underlying pathophysiology of GERD; and in vitro muscle strip studies of defects within the gastroesophageal sphincteric segment potentially leading to GERD.
Annals of the New York Academy of Sciences 09/2011; 1232(1):323-30. DOI:10.1111/j.1749-6632.2011.06073.x · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Relaxation of gastric clasp and sling muscle fibers is involved the transient lower esophageal sphincter relaxations underlying the pathophysiology of gastroesophageal reflux disease (GERD). These fibers do not contribute tone to the high-pressure zone in GERD patients, indicating their role in pathophysiology. This study identifies some mediators of the nicotine-induced relaxation of muscarinic receptor precontracted gastric clasp and sling fibers. Muscle strips from organ donors precontracted with bethanechol were relaxed with nicotine and then rechallenged after washing and adding inhibitors tetrodotoxin (TTX), the nitric-oxide synthase inhibitor L-nitro-arginine methyl ester (L-NAME), the β-adrenoceptor antagonist propranolol, the glycine receptor antagonist strychnine or ginkgolide B, and the GABA(A) receptor antagonist bicuculline or 2-(3-carboxypropyl)-3-amino-6-(4 methoxyphenyl)pyridazinium bromide [(gabazine) SR95531]. TTX only inhibited clasp fiber relaxations. L-NAME and propranolol inhibited, and ginkgolide B was ineffective in both. SR95531 was ineffective in clasp fibers and partially effective in sling fibers. Strychnine and bicuculline prevented relaxations with low potency, indicating actions not on glycine or GABA(A) receptors but more consistent with nicotinic receptor blockade. Bethanechol-precontracted fibers were relaxed by the nitric oxide donor S-nitroso-N-acetyl-DL-penicillamine and by the β-adrenergic agonist isoproterenol (clasp fibers only) but not by the glycine receptor agonist taurine or glycine or the GABA(A) agonist muscimol. These data indicate that nicotinic receptor activation mediates relaxation via release of nitric oxide in clasp and sling fibers, norepinephrine acting on β-adrenoceptors in clasp fibers, and GABA acting on GABA(A) receptors in sling fibers. Agents that selectively prevent these relaxations may be useful in the treatment of GERD.
Journal of Pharmacology and Experimental Therapeutics 04/2011; 338(1):37-46. DOI:10.1124/jpet.110.177097 · 3.97 Impact Factor