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Upper esophageal sphincter (UES) and pharyngeal (P) manometry: Which patients??
A410 AGA ABSTRACTS
GASTROENTEROLOGY Vol. 118, No.4
2128
2130
UPPER ESOPHAGEAL SPHINCTER (UES) AND PHARYNGEAL (P) MANOMETRY: WHICH PATIENTS?? Shuwen Xue, Philip O. Katz, June A. Castell, Donald O. Castell, Philadelphia, PA. Background: Dysphagia is a common symptom with various causes. Barium studies are the current standard for diagnosis. The value of DES and pharyngeal manometry has not been systematically evaluated. The aim of this study is to determine where DES function testing is appropriate. Methods: Manometry records of patients presenting with dysphagia (oropharyngeal and esophageal, N= 114, male 64, median age 70) as primary symptoms were reviewed. Eighty consecutive patients with heartburn (N=40, male 20, median age 51) or chest pain (N=40, male 12, median age 49) served as controls. Tracings evaluated for DES resting pressure, UES residual pressure, duration of UES relaxation, pharyngeal contraction and coordination of DES relaxation and pharyngeal contraction. Abnormalities shown below as percent of total patients. Chi square test was used to compare the 3 patient groups. Results: See table below. Summary: Dysphagia patients had significantly higher prevalence of high UES residual pressure, weak pharyngeal contraction and DES/pharyngeal in-coordination compared to patients presenting with other symptoms. No difference was found between heartburn and chest pain patients in any parameters studied. Seventy-one percent of dysphagia patients had at least one UESIP abnormality. Conclusion: UESIP manometry is frequently abnormal in patients presenting with dysphagia and may be useful as an adjunct to the barium study in diagnosis and treatment. RoutineUESIP evaluation is of low yield in other patients.
TRIGGERING OF RAPIDLY PROPAGATING PHASE I1I·LIKE ACTIVITY BY HIGH DOSAGE OF L-NMMA. Sjoerd D. Kuiken, Guido Nj Tytgat, Guy E. Boeckxstaens, AMC, Amsterdam, Netherlands; Acad Med Ctr, Amsterdam, Netherlands. It has been postulated that opoids and somatostatin induce phase III of the migrating motor complex (MMC) by reduction of nitric oxide (NO) production. In order to test this hypothesis we studied the effect of a high dose of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on fasting antral, pyloric and small intestinal motility in healthy volunteers. Methods: 10 male healthy volunteers (age 19-29 yr) were enrolled in a double blind placebo-controlled study evaluating the effect of L-NMMA (6.7mg/kglh LV.) on gastric and small intestinal motility. A 12 lumen perfused sleeve catheter was positioned beyond the ligament of Treitz with 3 antral side holes (1.5 em apart) and 6 small intestinal side holes (10 em apart). The position of the sleeve and 2 pyloric side holes across the pylorus was monitored using recording of the transmucosal potential difference. Baseline motility was recorded during 15 min before the infusion (placebo or L-NMMA) was started. Results: L-NMMA significantly increased diastolic blood pressure from 73:t7 to 83:t9 mmHg (p
Dys CP HB P
High UES Press.
High UES RP
Short Relax Our
Weak pharyn Cont
UESI pharyn In·co
Min Abnonn Param
14% 10% 13% 08
29% 2.5% 7.5% 00001
14% 5% 5% 0.13
25% 2.5% 2.5% 0.0002
32% 5% 13% 0.0006
71% 20% 38% 00001
2129
2131
CHOLINERGIC AND NITRERGIC NEUROTRANSMISSION IN CHRONICALLY INFLAMED ILEUM. Joris G. De Man, Tom G. Moreels, Benedicte Y. De Winter, Johannes 1. Bogers, Arnold G. Herman, Erik A. Van Marek, Paul A. Pelckmans, Univ Of Antwerp, Div of Gastroenterology, Antwerp, Belgium; Univ Antwerp, Antwerp, Belgium; Univ Of Antwerp, Div of Pharmacology, Antwerp, Belgium; Univ Of Antwerp, Div of Pathology, Antwerp, Belgium. We studied the effect of chronic inflammation on the cholinergic and nitrergic neurotransmision of the mouse ileum. Swiss mice were infected with the parasite S. mansoni. Fifteen weeks later, the ileum was removed and longitudinal muscle strips of control and infected mice were mounted in organ baths. Histology showed inflammatory granulomas, increased wall thickness and blunted villi in the ileum of infected but not of control mice. Contractions to electrical stimulation (ES 0.25-8Hz) and carbachol (CCh 1O-300nM) were significantly higher in inflamed ileum (ES 0.5 Hz: controls 0.26:t0.02g and inflamed 0.62:t0.04g, n=12). As contractions to 8Hz in controls (0.61:to.06g,n= 12) were of similar amplitude as those to 0.5Hz in inflamed ileum (0.62:t0.04g, n= 12) these frequencies were used for further study. I iLM atropine, a muscarinic blocker, abolished all contractions in control and inflamed ileum. The nicotinic blocker hexamethonium (HEXA l00iLM) did not affect contractions to CCh but inhibited those to ES more potently in inflamed than in control ileum (see table). The iNOS blocker methylisothiourea 3iLM had no effect. The nNOS blocker L-NNA 300iLM and the K+ channel blocker aminopyridine (AmPyr 10iLM) enhanced contractions to ES to a similar extent in control and inflamed ileum (see table) without changing contractions to CCh. L-type Ca++ channel blockade (nifedipine O.liLM) and depletion of cellular Ca++ stores (thapsigargin IiLM), reduced contractions to ES and CCh less potently in inflamed than in control ileum. In Ca++ free medium, 2.5mM CaCl 2 induced a transient direct muscle contraction that was significantly higher in inflamed ileum (0.24:t.O.05g vs 1.55:tO.02g). We conclude that in chronicallly inflamed ileum, contractions to ES of cholinergic nerves are hypersensitive to nicotinic blockers whereas direct smooth muscle contractions to CCh are hyposensitive to Ca ++ blockade. This suggests that chronic inflammation of the gut induces myogenic but also neuronal changes involving cholinergic but not nitrergic nerves.
ELECTRICAL MAPPING OF SPONTANEOUS PERISTALTIC REFLEXES IN THE ISOLATED FELINE DUODENUM. Wim 1. Lammers, John R. Slack, B. Stephen, O. Pozzan, Faculty of Medicine & Health Sci, AI Ain, UAE. In previous studies, we have reconstructed the spatial pattern of conduction of slow waves and of individual spikes (I) that are associated with mixing movements. In this study, an attempt was made to reconstruct the conduction pattern of the myo-electrical activity (peristaltic waves) associated with propulsive movement of the peristaltic reflex. Following anaesthesia, the duodenum was removed, opened along the mesenteric border and placed in a tissue bath. A multiple array of 24 x 10 extracellular electrodes (2 mm electrode distances) was gently positioned on the serosal surface of the preparation. Simultaneous recordings from all 240 extracellular electrodes were made during 15-30 minute periods (16 animals) and the pattern of propagation of slow waves and spontaneous peristaltic activations (n = 23) were analysed. Electrical signals associated with the peristaltic reflex have previously been identified by their large polyphasic deflections (2). Similar peristaltic complexes were found in our recordings. In the normal small intestine in vitro, both slow waves and peristaltic waves propagated aborally or orally as broad homogeneous waves. The direction of the peristaltic waves however was independent of that of the preceding slow wave (46% in the same direction; 54% in the opposite direction). Furthermore, the average conduction velocity of the peristaltic waves was significantly lower than that of the slow waves (1.00 cm/s :t 0.25 resp. 1.24 crn/s :t 0.29; p
control inflamed
HEXA
AmPyr
LNNA
Nlfedipine
Thapsigargin
-23±6'10 -94+5%+
+64±11% +56±16'10
+31±5'10 +30±9%
-61±14'10 -11±4'10+
-40±5% -5±5'10+
Results are expressed as%inhibition (-) or%enhancement (+) ofcontractions toES, +psO.05 is significantly different from controls (unpaired Students t test), n=6-8.
2132 SPIKES PROPAGATE IN DISCRETE, ISOLATED PATCHES IN THE FELINE SMALL INTESTINE IN VIVO. Wim J. Lammers, John R. Slack, B. Stephen, O. Pozzan, Faculty of Medicine & Health Sci, Al Ain, UAE. The temporal and spatial organisation of intestinal contractions is determined to a large extent by the propagation of slow waves and the initiation of spikes on top of these slow waves. Recently, in isolated segments of feline duodenum in vitro, we have demonstrated that individual spikes propagate in restricted domains or patches (I). The purpose of this study was to determine whether similar patches also occurred a) in other parts of the small intestine and b) in vivo. Following general anaesthesia and mid-abdominal incision, a multi-electrode array of 15 x 16 electrodes (1.4
GASTROENTEROLOGY Vol. 118, No.4
2128
2130
UPPER ESOPHAGEAL SPHINCTER (UES) AND PHARYNGEAL (P) MANOMETRY: WHICH PATIENTS?? Shuwen Xue, Philip O. Katz, June A. Castell, Donald O. Castell, Philadelphia, PA. Background: Dysphagia is a common symptom with various causes. Barium studies are the current standard for diagnosis. The value of DES and pharyngeal manometry has not been systematically evaluated. The aim of this study is to determine where DES function testing is appropriate. Methods: Manometry records of patients presenting with dysphagia (oropharyngeal and esophageal, N= 114, male 64, median age 70) as primary symptoms were reviewed. Eighty consecutive patients with heartburn (N=40, male 20, median age 51) or chest pain (N=40, male 12, median age 49) served as controls. Tracings evaluated for DES resting pressure, UES residual pressure, duration of UES relaxation, pharyngeal contraction and coordination of DES relaxation and pharyngeal contraction. Abnormalities shown below as percent of total patients. Chi square test was used to compare the 3 patient groups. Results: See table below. Summary: Dysphagia patients had significantly higher prevalence of high UES residual pressure, weak pharyngeal contraction and DES/pharyngeal in-coordination compared to patients presenting with other symptoms. No difference was found between heartburn and chest pain patients in any parameters studied. Seventy-one percent of dysphagia patients had at least one UESIP abnormality. Conclusion: UESIP manometry is frequently abnormal in patients presenting with dysphagia and may be useful as an adjunct to the barium study in diagnosis and treatment. RoutineUESIP evaluation is of low yield in other patients.
TRIGGERING OF RAPIDLY PROPAGATING PHASE I1I·LIKE ACTIVITY BY HIGH DOSAGE OF L-NMMA. Sjoerd D. Kuiken, Guido Nj Tytgat, Guy E. Boeckxstaens, AMC, Amsterdam, Netherlands; Acad Med Ctr, Amsterdam, Netherlands. It has been postulated that opoids and somatostatin induce phase III of the migrating motor complex (MMC) by reduction of nitric oxide (NO) production. In order to test this hypothesis we studied the effect of a high dose of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on fasting antral, pyloric and small intestinal motility in healthy volunteers. Methods: 10 male healthy volunteers (age 19-29 yr) were enrolled in a double blind placebo-controlled study evaluating the effect of L-NMMA (6.7mg/kglh LV.) on gastric and small intestinal motility. A 12 lumen perfused sleeve catheter was positioned beyond the ligament of Treitz with 3 antral side holes (1.5 em apart) and 6 small intestinal side holes (10 em apart). The position of the sleeve and 2 pyloric side holes across the pylorus was monitored using recording of the transmucosal potential difference. Baseline motility was recorded during 15 min before the infusion (placebo or L-NMMA) was started. Results: L-NMMA significantly increased diastolic blood pressure from 73:t7 to 83:t9 mmHg (p
Dys CP HB P
High UES Press.
High UES RP
Short Relax Our
Weak pharyn Cont
UESI pharyn In·co
Min Abnonn Param
14% 10% 13% 08
29% 2.5% 7.5% 00001
14% 5% 5% 0.13
25% 2.5% 2.5% 0.0002
32% 5% 13% 0.0006
71% 20% 38% 00001
2129
2131
CHOLINERGIC AND NITRERGIC NEUROTRANSMISSION IN CHRONICALLY INFLAMED ILEUM. Joris G. De Man, Tom G. Moreels, Benedicte Y. De Winter, Johannes 1. Bogers, Arnold G. Herman, Erik A. Van Marek, Paul A. Pelckmans, Univ Of Antwerp, Div of Gastroenterology, Antwerp, Belgium; Univ Antwerp, Antwerp, Belgium; Univ Of Antwerp, Div of Pharmacology, Antwerp, Belgium; Univ Of Antwerp, Div of Pathology, Antwerp, Belgium. We studied the effect of chronic inflammation on the cholinergic and nitrergic neurotransmision of the mouse ileum. Swiss mice were infected with the parasite S. mansoni. Fifteen weeks later, the ileum was removed and longitudinal muscle strips of control and infected mice were mounted in organ baths. Histology showed inflammatory granulomas, increased wall thickness and blunted villi in the ileum of infected but not of control mice. Contractions to electrical stimulation (ES 0.25-8Hz) and carbachol (CCh 1O-300nM) were significantly higher in inflamed ileum (ES 0.5 Hz: controls 0.26:t0.02g and inflamed 0.62:t0.04g, n=12). As contractions to 8Hz in controls (0.61:to.06g,n= 12) were of similar amplitude as those to 0.5Hz in inflamed ileum (0.62:t0.04g, n= 12) these frequencies were used for further study. I iLM atropine, a muscarinic blocker, abolished all contractions in control and inflamed ileum. The nicotinic blocker hexamethonium (HEXA l00iLM) did not affect contractions to CCh but inhibited those to ES more potently in inflamed than in control ileum (see table). The iNOS blocker methylisothiourea 3iLM had no effect. The nNOS blocker L-NNA 300iLM and the K+ channel blocker aminopyridine (AmPyr 10iLM) enhanced contractions to ES to a similar extent in control and inflamed ileum (see table) without changing contractions to CCh. L-type Ca++ channel blockade (nifedipine O.liLM) and depletion of cellular Ca++ stores (thapsigargin IiLM), reduced contractions to ES and CCh less potently in inflamed than in control ileum. In Ca++ free medium, 2.5mM CaCl 2 induced a transient direct muscle contraction that was significantly higher in inflamed ileum (0.24:t.O.05g vs 1.55:tO.02g). We conclude that in chronicallly inflamed ileum, contractions to ES of cholinergic nerves are hypersensitive to nicotinic blockers whereas direct smooth muscle contractions to CCh are hyposensitive to Ca ++ blockade. This suggests that chronic inflammation of the gut induces myogenic but also neuronal changes involving cholinergic but not nitrergic nerves.
ELECTRICAL MAPPING OF SPONTANEOUS PERISTALTIC REFLEXES IN THE ISOLATED FELINE DUODENUM. Wim 1. Lammers, John R. Slack, B. Stephen, O. Pozzan, Faculty of Medicine & Health Sci, AI Ain, UAE. In previous studies, we have reconstructed the spatial pattern of conduction of slow waves and of individual spikes (I) that are associated with mixing movements. In this study, an attempt was made to reconstruct the conduction pattern of the myo-electrical activity (peristaltic waves) associated with propulsive movement of the peristaltic reflex. Following anaesthesia, the duodenum was removed, opened along the mesenteric border and placed in a tissue bath. A multiple array of 24 x 10 extracellular electrodes (2 mm electrode distances) was gently positioned on the serosal surface of the preparation. Simultaneous recordings from all 240 extracellular electrodes were made during 15-30 minute periods (16 animals) and the pattern of propagation of slow waves and spontaneous peristaltic activations (n = 23) were analysed. Electrical signals associated with the peristaltic reflex have previously been identified by their large polyphasic deflections (2). Similar peristaltic complexes were found in our recordings. In the normal small intestine in vitro, both slow waves and peristaltic waves propagated aborally or orally as broad homogeneous waves. The direction of the peristaltic waves however was independent of that of the preceding slow wave (46% in the same direction; 54% in the opposite direction). Furthermore, the average conduction velocity of the peristaltic waves was significantly lower than that of the slow waves (1.00 cm/s :t 0.25 resp. 1.24 crn/s :t 0.29; p
control inflamed
HEXA
AmPyr
LNNA
Nlfedipine
Thapsigargin
-23±6'10 -94+5%+
+64±11% +56±16'10
+31±5'10 +30±9%
-61±14'10 -11±4'10+
-40±5% -5±5'10+
Results are expressed as%inhibition (-) or%enhancement (+) ofcontractions toES, +psO.05 is significantly different from controls (unpaired Students t test), n=6-8.
2132 SPIKES PROPAGATE IN DISCRETE, ISOLATED PATCHES IN THE FELINE SMALL INTESTINE IN VIVO. Wim J. Lammers, John R. Slack, B. Stephen, O. Pozzan, Faculty of Medicine & Health Sci, Al Ain, UAE. The temporal and spatial organisation of intestinal contractions is determined to a large extent by the propagation of slow waves and the initiation of spikes on top of these slow waves. Recently, in isolated segments of feline duodenum in vitro, we have demonstrated that individual spikes propagate in restricted domains or patches (I). The purpose of this study was to determine whether similar patches also occurred a) in other parts of the small intestine and b) in vivo. Following general anaesthesia and mid-abdominal incision, a multi-electrode array of 15 x 16 electrodes (1.4