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M2040 Alteration of Phonation Induced UES Contractile Response in Patients With Posterior Laryngitis
AGA Abstracts
models. The expression of submucous 5-HT3 receptor was evaluated by real time RT-PCR and Western blot analysis. Results: In the basal condition, somatostatin accumulation in the supernatant of rat colonic mucosa/submucosa preparations was 77.8 ± 13.96 pg*g-1 (n = 7). Incubation of the colonic mucosa/submucosa preparations with 5-HT (10 μM) caused an increase in the concentration of somatostatin (135.9 ± 6.78 pg*g-1; n = 6; p<0.01). Pretreatment with the 5-HT3 antagonists, MDL72222 (0.1 μM) or Tropanyl-3, 5-dimethylbenzoate (0.1 μM), significantly inhibited 5-HT-induced somatostatin release to 74.5 ± 28.1 pg*g-1 (n = 6, p < 0.05) and 91.1 ± 19.7 pg*g-1 (n = 5, p < 0.05), respectively. The SSTR2 antagonist, CYN 154806 (0.5 μM), did not affect 5-HT-induced somatostatin release. In the condition of WIR, the expression of mRNA and protein of submucous 5-HT3 receptor was significantly decreased. Baseline transepithelial resistance of the colonic mucosa/submucosa preparations in WIR rats was significantly lower (55.8 ± 3.2 Ω*cm2, n = 11) than that in control rats (67.8 ± 3.7 Ω*cm2, n = 11, p<0.01). Moreover, 5-HT-evoked ΔISC was enhanced from 740.2 ± 69.2 μA*min in control rats to 1321.0 ± 162.5 μA*min in WIR rats (n = 11, p<0.001). In WIR rats, 5-HT3 receptor antagonists, MDL72222 (0.01 μM), did not increase, but decrease 5-HT-induced ΔISC to 955.3 ± 130.9 μA*min from 1325.0 ± 182.9 μA*min (n = 9, p<0.05). Conclusions: 5-HT, during its promoting colonic secretion, can also elicit a regulatory effect of negative feedback by activating submucous neuronal 5-HT3 receptor and somatostatin release. In condition of stress, this effect of negative feedback may be inhibited. M2038 M2040 Simultaneous Multi-Point Measurement of Circumferential and Longitudinal Activity Recorded in Isolated Mammalian Lumen Using a Multimodal Fibre Optic Catheter Philip G. Dinning, John W. Arkwright, Ian Underhill, Michal M. Szczesniak, Simon J. Brookes, Marcello Costa, Nicholas J. Spencer
Alteration of Phonation Induced UES Contractile Response in Patients With Posterior Laryngitis Kulwinder S. Dua, Manuel A. Amaris, Sohrab Rahimi Naini, Benjamin Schneeberger, Arash Babaei, Shiko Kuribayashi, Joel H. Blumin, Reza Shaker BACKGROUND: Rise in intra-abdominal pressure during phonation can predispose to esophageal reflux of gastric contents. Recent studies in healthy volunteers have shown the existence of phonation-induced rise in UES pressure thereby protecting the airways from refluxate during phonation. AIM: To investigate the integrity of phonation induced UES contractile response in patients with posterior laryngitis (PL). METHODS: We studied 10 consecutive patients with ENT diagnosis of PL (6 F, age 62.4 ± 16 SD yr ) with 10 matched healthy controls (6 F, 58 ± 24 yr). Phonation induced UES pressure changes were determined using previously described techniques (Perera et al Am J Physiol 2007;G885-91) of concurrent high resolution manometry (Manoscan, Sierra Scientific) and voice recordings analyzed by Praat® software (Praat, University of Amsterdam). We tested high and low pitch vowels (a¯, ê) for phonation duration of 10 seconds X 3. RESULTS: The basal UES pressure was significantly lower in the PL group compared to healthy controls. The median basal pressure for all sounds was 34 mmHg (12, 73) [median (min, max)] in the healthy group and 22(5,159) in the laryngitis group. Three types of UES response to phonation were observed: Type 1, Sustained UES contractile response 57 mmHg (7, 467), 42(5, 337) above baseline in healthy controls and PL patients respectively. ; Type 2, biphasic response which includes contraction with periods of partial relaxation (~ 40% below baseline), Type 3, sustained UES partial relaxation(~40% pressure below the baseline). Patients with PL exhibited significantly more biphasic and partial relaxation response Compared to controls (figure). CONCLUSIONS: Phonation induced UES contractile response is deteriorated in patients with posterior laryngitis. Supported in part by research grants 1PO1DKO68061-01A1, 5RO1DKO2573128 and T32 DK61923.
Background: Recent studies in the human oesophagus have demonstrated that the circular and longitudinal muscle layers contract in a precise synchronous fashion during peristalsis. These data have been largely been derived from combined manometry and ultrasonography studies and are limited in that they can only assess muscle activity at one or two sites along the lumen at any given time. Utilizing fibre-optic sensing technology we have developed a catheter capable of recording longitudinal and circumferential motor activity across multiple sites simultaneously. Aim: to validate this tool in the isolated mammalian lumen. Method: The catheters were fabricated from multiple fibre Bragg grating (fbg) elements written into a continuous length of single mode fiber. Each catheter contained 5 pressure sensors and 5 longitudinal sensors spaced alternately every 15 mm from the catheter tip. The sensors were based on recently published manometry devices and adding a sliding collar in contact with the fibre and lying underneath the outer silicone sleeve recorded the longitudinal sensitivity. The diameter of the catheter was 3.6mm. Segments of rabbit small intestine (30 cm; n=3) were placed in an organ bath with Krebs at 36oC. The catheter was inserted into the ileum. Pendulum movement of the rabbit ileum occurred spontaneously and to elicit slowly propagated contractions we introduced erythromycin (10-6M) into the bath. Motor activity recorded by the optical catheter was temporally correlated with simultaneous video clips taken of the luminal wall movements. Results: Longitudinal and circumferential motility was identified from the video clips. The longitudinal motion sensors and pressure sensors also detected periods of motility with the longitudinal motion clearly distinguishable from the circumferential contractions. Analysis revealed a tight correlation was found between manometric and video recordings with 97% of activity detected by the longitudinal and pressure sensors identified visually. Conclusions: Fibre optic catheters can be used to monitor changes in both longitudinal and circular contraction from multiple sites within isolated segments of intestine. In the human esophagus this ability could dramatically enhance our understanding of the normal physiology in health and subsequently the abnormalities in patients. M2039 Influence of Neck Positions on Airway Protetive Mechanisms Manuel A. Amaris, Kulwinder S. Dua, Sohrab Rahimi Naini, Sri Naveen Surapaneni, Reza Shaker BACKGROUND: Aerodigestive reflexes have been proposed to protect the airways against aspiration. Laryngeal spillage of fluid is seen in those with defective reflexes. The maximum volume of water that the hypopharynx can accommodate before spilling into the larynx, namely Hypopharyngeal Safe-volume (HPSV) has been determined in these subjects with the neck in neutral position. AIM: To determine the effect of neck position on the threshold volume required to elicit Pharyngo-UES contractile reflex (PUCR), Reflexive Pharyngeal Swallow (RPS), and HPSV. METHODS: Eight healthy subjects (age 25±2 yrs, F 5) were studied in semi-recumbent position. PUCR and RPS were elicited using previously described techniques of concurrent UES manometry (sleeve), submental EMG and transnasal pharyngolaryngoscopy. Water was infused (1ml/min) into the posterior pharynx 2 cm above UES with the neck in neutral, flexion and extension positions. HPSV was determined after abolishing RPS with topical pharyngeal anesthesia and measuring the volume of water required to reach the superior margin of the inter-arytenoid notch before spilling into the larynx. RESULTS: The threshold volume required to trigger PUCR and RPS was significantly higher in neck flexion compared to the neck in extended position (figure). The HPSV was significantly lower in neck extension compared to the other neck positions (figure). CONCLUSIONS: The amount of fluid that can safely dwell in the pharynx before spilling into the larynx as well as the threshold volumes needed to trigger pharyngeal reflexes are influenced by neck position. During flexion and neutral positions larger volumes are safely accommodated in the pharynx compared to neck extension.
AGA Abstracts
M2041 Intragastric Monosodium L-Glutamate Stimulates Motility of the Upper Gut via the Vagus Nerve in Conscious Dogs Yoshitaka Toyomasu, Erito Mochiki, Atsushi Ogawa, Hiroki Morita, Mitsuhiro Yanai, Kyoichi Ogata, Yuichi Tabe, Hiroyuki Andoh, Tetsuro Ohno, Hiroaki Zai, Hiroyuki Kuwano Background & Aims: Monosodium L-glutamate (MSG) is known to bind to receptors on taste cells in the oral cavity and to elicit the umami taste and stimulate secretions from the exocrine and gastrointestinal endocrine systems. Recent studies indicate that the receptor, T1Rs and mGluR1, are also expressed in the upper gastrointestinal mucosa of humans, rats, and mice. The physiological studies have reported that intragastric administration of MSG increases the firing rate of afferent fibers in the gastric branch of the rat vagus nerve. Furthermore, intragastric administration of MSG has induced activation in forebrain regions via the vagus nerves. However, the effect of intraluminal administration of MSG on upper gut motility has not been investigated. The aim of our study is to investigate whether direct intragastric MSG stimulates gut motility and to identify the mechanism in conscious dogs. Methods: Contractile response to intraluminal injection of MSG was studied in the fed and fasted state by means of chronically implanted force transducers. MSG (5, 15, 45, and 90
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models. The expression of submucous 5-HT3 receptor was evaluated by real time RT-PCR and Western blot analysis. Results: In the basal condition, somatostatin accumulation in the supernatant of rat colonic mucosa/submucosa preparations was 77.8 ± 13.96 pg*g-1 (n = 7). Incubation of the colonic mucosa/submucosa preparations with 5-HT (10 μM) caused an increase in the concentration of somatostatin (135.9 ± 6.78 pg*g-1; n = 6; p<0.01). Pretreatment with the 5-HT3 antagonists, MDL72222 (0.1 μM) or Tropanyl-3, 5-dimethylbenzoate (0.1 μM), significantly inhibited 5-HT-induced somatostatin release to 74.5 ± 28.1 pg*g-1 (n = 6, p < 0.05) and 91.1 ± 19.7 pg*g-1 (n = 5, p < 0.05), respectively. The SSTR2 antagonist, CYN 154806 (0.5 μM), did not affect 5-HT-induced somatostatin release. In the condition of WIR, the expression of mRNA and protein of submucous 5-HT3 receptor was significantly decreased. Baseline transepithelial resistance of the colonic mucosa/submucosa preparations in WIR rats was significantly lower (55.8 ± 3.2 Ω*cm2, n = 11) than that in control rats (67.8 ± 3.7 Ω*cm2, n = 11, p<0.01). Moreover, 5-HT-evoked ΔISC was enhanced from 740.2 ± 69.2 μA*min in control rats to 1321.0 ± 162.5 μA*min in WIR rats (n = 11, p<0.001). In WIR rats, 5-HT3 receptor antagonists, MDL72222 (0.01 μM), did not increase, but decrease 5-HT-induced ΔISC to 955.3 ± 130.9 μA*min from 1325.0 ± 182.9 μA*min (n = 9, p<0.05). Conclusions: 5-HT, during its promoting colonic secretion, can also elicit a regulatory effect of negative feedback by activating submucous neuronal 5-HT3 receptor and somatostatin release. In condition of stress, this effect of negative feedback may be inhibited. M2038 M2040 Simultaneous Multi-Point Measurement of Circumferential and Longitudinal Activity Recorded in Isolated Mammalian Lumen Using a Multimodal Fibre Optic Catheter Philip G. Dinning, John W. Arkwright, Ian Underhill, Michal M. Szczesniak, Simon J. Brookes, Marcello Costa, Nicholas J. Spencer
Alteration of Phonation Induced UES Contractile Response in Patients With Posterior Laryngitis Kulwinder S. Dua, Manuel A. Amaris, Sohrab Rahimi Naini, Benjamin Schneeberger, Arash Babaei, Shiko Kuribayashi, Joel H. Blumin, Reza Shaker BACKGROUND: Rise in intra-abdominal pressure during phonation can predispose to esophageal reflux of gastric contents. Recent studies in healthy volunteers have shown the existence of phonation-induced rise in UES pressure thereby protecting the airways from refluxate during phonation. AIM: To investigate the integrity of phonation induced UES contractile response in patients with posterior laryngitis (PL). METHODS: We studied 10 consecutive patients with ENT diagnosis of PL (6 F, age 62.4 ± 16 SD yr ) with 10 matched healthy controls (6 F, 58 ± 24 yr). Phonation induced UES pressure changes were determined using previously described techniques (Perera et al Am J Physiol 2007;G885-91) of concurrent high resolution manometry (Manoscan, Sierra Scientific) and voice recordings analyzed by Praat® software (Praat, University of Amsterdam). We tested high and low pitch vowels (a¯, ê) for phonation duration of 10 seconds X 3. RESULTS: The basal UES pressure was significantly lower in the PL group compared to healthy controls. The median basal pressure for all sounds was 34 mmHg (12, 73) [median (min, max)] in the healthy group and 22(5,159) in the laryngitis group. Three types of UES response to phonation were observed: Type 1, Sustained UES contractile response 57 mmHg (7, 467), 42(5, 337) above baseline in healthy controls and PL patients respectively. ; Type 2, biphasic response which includes contraction with periods of partial relaxation (~ 40% below baseline), Type 3, sustained UES partial relaxation(~40% pressure below the baseline). Patients with PL exhibited significantly more biphasic and partial relaxation response Compared to controls (figure). CONCLUSIONS: Phonation induced UES contractile response is deteriorated in patients with posterior laryngitis. Supported in part by research grants 1PO1DKO68061-01A1, 5RO1DKO2573128 and T32 DK61923.
Background: Recent studies in the human oesophagus have demonstrated that the circular and longitudinal muscle layers contract in a precise synchronous fashion during peristalsis. These data have been largely been derived from combined manometry and ultrasonography studies and are limited in that they can only assess muscle activity at one or two sites along the lumen at any given time. Utilizing fibre-optic sensing technology we have developed a catheter capable of recording longitudinal and circumferential motor activity across multiple sites simultaneously. Aim: to validate this tool in the isolated mammalian lumen. Method: The catheters were fabricated from multiple fibre Bragg grating (fbg) elements written into a continuous length of single mode fiber. Each catheter contained 5 pressure sensors and 5 longitudinal sensors spaced alternately every 15 mm from the catheter tip. The sensors were based on recently published manometry devices and adding a sliding collar in contact with the fibre and lying underneath the outer silicone sleeve recorded the longitudinal sensitivity. The diameter of the catheter was 3.6mm. Segments of rabbit small intestine (30 cm; n=3) were placed in an organ bath with Krebs at 36oC. The catheter was inserted into the ileum. Pendulum movement of the rabbit ileum occurred spontaneously and to elicit slowly propagated contractions we introduced erythromycin (10-6M) into the bath. Motor activity recorded by the optical catheter was temporally correlated with simultaneous video clips taken of the luminal wall movements. Results: Longitudinal and circumferential motility was identified from the video clips. The longitudinal motion sensors and pressure sensors also detected periods of motility with the longitudinal motion clearly distinguishable from the circumferential contractions. Analysis revealed a tight correlation was found between manometric and video recordings with 97% of activity detected by the longitudinal and pressure sensors identified visually. Conclusions: Fibre optic catheters can be used to monitor changes in both longitudinal and circular contraction from multiple sites within isolated segments of intestine. In the human esophagus this ability could dramatically enhance our understanding of the normal physiology in health and subsequently the abnormalities in patients. M2039 Influence of Neck Positions on Airway Protetive Mechanisms Manuel A. Amaris, Kulwinder S. Dua, Sohrab Rahimi Naini, Sri Naveen Surapaneni, Reza Shaker BACKGROUND: Aerodigestive reflexes have been proposed to protect the airways against aspiration. Laryngeal spillage of fluid is seen in those with defective reflexes. The maximum volume of water that the hypopharynx can accommodate before spilling into the larynx, namely Hypopharyngeal Safe-volume (HPSV) has been determined in these subjects with the neck in neutral position. AIM: To determine the effect of neck position on the threshold volume required to elicit Pharyngo-UES contractile reflex (PUCR), Reflexive Pharyngeal Swallow (RPS), and HPSV. METHODS: Eight healthy subjects (age 25±2 yrs, F 5) were studied in semi-recumbent position. PUCR and RPS were elicited using previously described techniques of concurrent UES manometry (sleeve), submental EMG and transnasal pharyngolaryngoscopy. Water was infused (1ml/min) into the posterior pharynx 2 cm above UES with the neck in neutral, flexion and extension positions. HPSV was determined after abolishing RPS with topical pharyngeal anesthesia and measuring the volume of water required to reach the superior margin of the inter-arytenoid notch before spilling into the larynx. RESULTS: The threshold volume required to trigger PUCR and RPS was significantly higher in neck flexion compared to the neck in extended position (figure). The HPSV was significantly lower in neck extension compared to the other neck positions (figure). CONCLUSIONS: The amount of fluid that can safely dwell in the pharynx before spilling into the larynx as well as the threshold volumes needed to trigger pharyngeal reflexes are influenced by neck position. During flexion and neutral positions larger volumes are safely accommodated in the pharynx compared to neck extension.
AGA Abstracts
M2041 Intragastric Monosodium L-Glutamate Stimulates Motility of the Upper Gut via the Vagus Nerve in Conscious Dogs Yoshitaka Toyomasu, Erito Mochiki, Atsushi Ogawa, Hiroki Morita, Mitsuhiro Yanai, Kyoichi Ogata, Yuichi Tabe, Hiroyuki Andoh, Tetsuro Ohno, Hiroaki Zai, Hiroyuki Kuwano Background & Aims: Monosodium L-glutamate (MSG) is known to bind to receptors on taste cells in the oral cavity and to elicit the umami taste and stimulate secretions from the exocrine and gastrointestinal endocrine systems. Recent studies indicate that the receptor, T1Rs and mGluR1, are also expressed in the upper gastrointestinal mucosa of humans, rats, and mice. The physiological studies have reported that intragastric administration of MSG increases the firing rate of afferent fibers in the gastric branch of the rat vagus nerve. Furthermore, intragastric administration of MSG has induced activation in forebrain regions via the vagus nerves. However, the effect of intraluminal administration of MSG on upper gut motility has not been investigated. The aim of our study is to investigate whether direct intragastric MSG stimulates gut motility and to identify the mechanism in conscious dogs. Methods: Contractile response to intraluminal injection of MSG was studied in the fed and fasted state by means of chronically implanted force transducers. MSG (5, 15, 45, and 90
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