- Email: [email protected]
Effects of baclofen on postprandial fundic tone and lower esophageal sphincter function in man
pain episodes. For each pain episode we calculated esophageal shortening as the difference in length between emitter and receiver during 2rain before to 30 sec after pain and the 2.5min preceding period. Acid reflux and/or high amplitude or simultaneous contractions were checked dunng the same periods Results: Recordings were technically satisfactory (> 15hs) in 6 patients. Esophageal shortening could not be measured in 2 patients due to early loss of the emitter mucosal clip. One patient was asymptomatic dunng the study. We analysed 46 pain events in 5 patients (1-16/pat). In 4 patients, 16 pain events (f-7/pat) were associated with a prolonged oral LES excursion of 7.8 • 06 ram. Esophageal shortening started 7 0 -+ 10 sec before the pain events and lasted 124-+26sec. Acid reflux was present in 5 and abnormal manometry in 10 pain events associated with esophageal shortening. Conclusion: Continuous ambulatory monitoring of esophageal shortening in man is possible. Ongoing studies will provide further information about the possible association between esophageal symptoms and abnormal contraction of the esophageal longitudinal muscle leading to prolonged esophageal shortening.
873 A Double Blind, Placebo Controlled Cross-over Study Of Oral Theophylline In Functional Chest Pain Ranjit Mudipafli, Xing Zhao, Craig Utech, Joan Kemp[ Satish Rao The treatment of functional chest pain is unsatisfactory and there is no approved drug. We have shown that IV tbeophylline improves esophageal hypersensitivity in patients with functional chest pain possibly by altering nociception (Am J Gastroenterol 2002; 97:$5). Our aim was to investigate the effects of oral theophylfine, a non-specific adenosine receptor antagonist in patients with chest pain of esophageal origin. Methods: Twenty five (M/F = 7/ 18) patients with non cardiac, non-GERD esophageal chest pain and hypersensitivity to balloon distention were randomized to receive either theophynine SR 200 mg PO bid or placebo for 8 weeks, in a double blind cross over study. The frequency, intensity and duration of chest pain were recorded for two weeks at baseline, during theophylline and placebo phases and simultaneously psychosocial and quality of life measures (SCL- 90 & SF-36) were obtained. Results: 19 patients (M/F=4/15) completed the study. During the theophylline phase, the mean frequency, intensity and duration of chest pain improved (p(0.05) when compared to baseline, (see Table = mean • sd. * = p(0.05, Baseline vs Theophylline and t = p(0.05, Theophylline vs Placebo).. In contrast, there was no change during the placebo phase. The overall change in symptoms was rated as (theophylline vs placebo) better in 11 (58%) vs 1(6%), p(0.05, worse in 4 (21%) vs 5(26%) and unchanged in 4 (21%) vs 13 (68 %), p (0.05. Six patients dropped out of the study because of compliance (n= 3) and protocol violation (n = 3). Adverse effects on theophylfine were nausea (2), insomnia (1), tremor (1), and flghtheadedness (1) and on placebo were palpitations (1) and insomnia (1), but none discontinued participation. Psychosocial and quality of life data showed that social functioning improved on theophylline (p = 0.02) but not on placebo but bodily pain, physical function, phobia, depression and anxiety scores were unchanged. Conclusions: Theophyfline was well tolerated and sigmhcantly decreased the frequency and intensity of functional chest pain in 60% of patients. Thus, a non-selective adenosine receptor antagonist such as theophylline can be useful in the treatment of visceral pain. We hope that this study may serve as an impetus for the development of gut-selective adenosine receptor antagonists for the treatment of functional chest pain.
871 Combined Multichannel Intraluminal Impedance and Esophageal Manometry (MII-EM) Clarifies Function Defects During Swallowing Radn Tutuian, Lileeth Kong, Shirley Jamison, June A. Caste[1, Donald O. Castefl Background Combined manometry and muhichannel mtraluminal impedance (MII-EM) allows simultaneous assessment of bolus transit (by MI1) and pressure generation (by EM) within the esophagus. Using combined MII-EM swallows can be classified manometricafly as either normal peristaltic, ineffective or simultaneous and by MII as having complete or incomplete bolus transit. The aim of this study is to evaluate manometric factors influencing complete vs. incomplete bolus transit in patients referred for esophageal function testing. Methods Combined MII-EM studies from 150 consecutive patients referred to our laboratory were evaluated comparing results obtained with individual swallows. Manometric diagnoses included normal manometry (33%), ineffective esophageal motility (17%), achalasia (11%), distal esophageal spasm (11%), poorly relaxing LES (11%), nutcracker esophagus (10%), hypertensive LES (5%), hypotensive LES (2%) Results The 150 patients described above completed a total of 1464 liquid swallows, characterized by MII as having complete or incomplete bolus transit. Data are presented in the table below according to manometric characteristics of indivadna[ swallow. Summary Incomplete bolus transit is associated with lower contraction amplitudes in the distal part of the esophagus. Manometric ineffective swallows with incomplete bolus transit had higher LES residual pressure compared to those with complete bolus transit. Conclusion These results suggest that contraction amplitude in the distal esophagus is the major determinant of bolus transit. Esophageal function testing using combined MII-EM helps clarify the interaction between esophageal body and 1-ES that enables bolus transit V prwsure tOcm~ve LES Pres=ure 5cmabo~ LES D~tal esophil ampltude LESP.N~ t~l Prmemrl
~rtT~ pedshd~ iniithlCtlv4 p~lalld II r p-vitue IncomplVe ~ p-v~=e
~
~
conb'actl~ll complet, p-vllue
988 , 165
1143 ' 21
0.294
184 07
255 14
0.001
598 6.3
1280 9.3
821 ' 114
1281 22
0003
219 ' 12
515 40
0001
62.2 - 82
157.3 . 11.8 0001
90.5 ' 117
1212 20
0.026
203 ~08
39.2 20
0001
610"67
1427 10.0 0.001
0.738
8107
47 0.4
0001
5607
62 11
5801
?7 1.0
#ofpalnepisodes # o f pain f T e e d a y t J 2 w k s Intensity of pain
Theophylline
2 0 { 13) 5(,4) 3(1)
1 2 ( 12)'1 7(, 5)'1" 2.5(:1.4)*
Natural History of Primary Eosinophilic Esophagitis: A Follow-Up of 30 Adult Patients for up to 12 Years Alex Straumann, Hans-Peter Spichtin, Hans-Uwe Simon, Mauro Pirovino, Christoph Beglinger
0001
Primary eosmophilic esophagitis (PEE) is an increasingly recognized, IL-5 driven inflammatory disorder of the esophagus. The only presenting symptom m adults is uniform attacks of dysphagia. PEE is histologically characterized by a dense infiltration of the esophageal epithelium with eosinophils. To date, the natural course of PEE has not been defined, and information regarding its potential long-term naks is still lacking. To our knowledge, this study is the first characterizing the natural course of PEE. Thirty adult patients (22 males and 8 females; mean age 40.6 years) with previously confirmed PEE were included in this study. The criteria for inclusion were: 1. typical history; 2. infiltration of the esophageal epithelium with > 24 eosinophils/hpf at the baseline examination; 3. time span > 1 year since diagnosis. GERD was excluded clinically, endoscopically and by 24-hour pH probe monitoring. After a mean follow-up time of 6.2 years (range 1.4 - 11.5), all patients underwent a foflow-up examination, consisting of a structured interview, physical examination, hematological and blood chemical analysis, determination of lymphocyte subpopulations in blood and EGD with histological examination of the esophageal, gastric and duodenal mucosa. All patients survived the study period and remained in good health. The dysphagia persisted in 28 patients and had, m 1 patient a major, and in 15, a minor negative impact on socioprofessional activities. Patients with blood eosinophiha had significantly more dysphagia attacks. The nutritional state remained stable (BMI 23.5 vs. 24.6; serum albumin 45.5 vs. 44.2). The eosinophilic infiltration of the esophagus persisted in all symptomatic patients, but the cell number decreased significantly (78.7 vs. 40.3 cells/hpi). The inflammatory process did not spread to the stomach or duodenum, but did evoke fibrosis of the esophageal lamina propria. Dysplasias or malignant esophageal conditions were not detected either endoscopically or histologically, and no lympho-proliferative diseases occurred. Based on this long-term observation of 30 adult patients, we conclude that PEE is almost always a primary-chronic disease, restricted to the esophagus It leads to persistent dysphagia and structural alterations of the esophageal tissue, but does not have an impact on the nutritional state. Furthermore, no disabling or malignant potential has been associated with this disease.
0138
Effects of Baclofen on Postprandial Fundic Tone and Lower Esophageal Sphincter Function in Man Kwang-Jae Lee, Rita Vos, Jozef Janssens, Jan Tack Background: The GABAB agonist baclofen was shown to inhibit transient lower esophageal sphincter relaxations (TLESRs) and to increase postprandial LES pressure in health and in reflux disease. Meal-induced increases in fundic volume trigger the reflex pathway underlying TLESRs, but the effect of baclofen on gastric meal accommodation is unknown. The aim of the study was to assess the effect of baclofen on postprandial fundic tone and LES function in man. Methods: Studies were performed in 7 healthy subjects (4 males: mean age 28 + 2 D's). After an overnight fast, a barostat bag was placed into the gastric fundus and a sleeve manometry catheter with pH electrode was positioned in the esophagus. With the harostat at MDP + 2 mmHg, recordings of fundic tone, esophageal manometry and esophageal pI-I were performed for 3.5 hours after oral ingestion of 40 mg baclofen or placebo in a randomized, double-blind manner. After 90 min, subjects ingested a liquid meal (200 mL, 300 kcal) Results: Ihe number of TLESP,s increased from 0.6_+0.3/h during fasting to 3.1_+ 0.5 and 2.1-+0.5/h during 1st and 2nd postprandial hour, respectively (p<0.05). Baclofen significantly reduced TLESR rate during 1st and 2nd postprandial hour (respectively, 0.6 -+ 0.3/h and 0 4 -+ 03/h; p
Abstracts
Placebo
17(14) 5(4) 3.3(,0.9)
874
872
AGA
Baseline
875 Plasma Ghrelin following Cure of Helicobacter pylori Dennis A. Freshwater, Paul O'Hare, Harpal S. Randeva, Chuka U Nwokohi Background: In the western world, the incidence of oesophageal adenocarcinoma has increased over the last 30 years coinciding with a decrease in the prevalence of Helicobacter pylori. Trends of increasing oesophageal adenocarcinoma can be linked causally to increasing gastroesophageal reflux disease (GORD) which can be linked to an increasingly obese population. However there is no plausible biological mechanism of association between Helicobacter pylori, obesity and GORD. Ghrelin, a peptide produced in the stomach, which regulates appetite, food intake and body composition as studied in Heflcobacter pylori positive asymptomatic subjects. Methods: Plasma ghrelin, leptin and gastrin were measured for 6 hours after an overnight fast, before and after cure of Helicohacter pylon in ten subjects. Twenty-four hour intragastric acidity was also assessed. Results: After cure median (95%
A-122
873 A Double Blind, Placebo Controlled Cross-over Study Of Oral Theophylline In Functional Chest Pain Ranjit Mudipafli, Xing Zhao, Craig Utech, Joan Kemp[ Satish Rao The treatment of functional chest pain is unsatisfactory and there is no approved drug. We have shown that IV tbeophylline improves esophageal hypersensitivity in patients with functional chest pain possibly by altering nociception (Am J Gastroenterol 2002; 97:$5). Our aim was to investigate the effects of oral theophylfine, a non-specific adenosine receptor antagonist in patients with chest pain of esophageal origin. Methods: Twenty five (M/F = 7/ 18) patients with non cardiac, non-GERD esophageal chest pain and hypersensitivity to balloon distention were randomized to receive either theophynine SR 200 mg PO bid or placebo for 8 weeks, in a double blind cross over study. The frequency, intensity and duration of chest pain were recorded for two weeks at baseline, during theophylline and placebo phases and simultaneously psychosocial and quality of life measures (SCL- 90 & SF-36) were obtained. Results: 19 patients (M/F=4/15) completed the study. During the theophylline phase, the mean frequency, intensity and duration of chest pain improved (p(0.05) when compared to baseline, (see Table = mean • sd. * = p(0.05, Baseline vs Theophylline and t = p(0.05, Theophylline vs Placebo).. In contrast, there was no change during the placebo phase. The overall change in symptoms was rated as (theophylline vs placebo) better in 11 (58%) vs 1(6%), p(0.05, worse in 4 (21%) vs 5(26%) and unchanged in 4 (21%) vs 13 (68 %), p (0.05. Six patients dropped out of the study because of compliance (n= 3) and protocol violation (n = 3). Adverse effects on theophylfine were nausea (2), insomnia (1), tremor (1), and flghtheadedness (1) and on placebo were palpitations (1) and insomnia (1), but none discontinued participation. Psychosocial and quality of life data showed that social functioning improved on theophylline (p = 0.02) but not on placebo but bodily pain, physical function, phobia, depression and anxiety scores were unchanged. Conclusions: Theophyfline was well tolerated and sigmhcantly decreased the frequency and intensity of functional chest pain in 60% of patients. Thus, a non-selective adenosine receptor antagonist such as theophylline can be useful in the treatment of visceral pain. We hope that this study may serve as an impetus for the development of gut-selective adenosine receptor antagonists for the treatment of functional chest pain.
871 Combined Multichannel Intraluminal Impedance and Esophageal Manometry (MII-EM) Clarifies Function Defects During Swallowing Radn Tutuian, Lileeth Kong, Shirley Jamison, June A. Caste[1, Donald O. Castefl Background Combined manometry and muhichannel mtraluminal impedance (MII-EM) allows simultaneous assessment of bolus transit (by MI1) and pressure generation (by EM) within the esophagus. Using combined MII-EM swallows can be classified manometricafly as either normal peristaltic, ineffective or simultaneous and by MII as having complete or incomplete bolus transit. The aim of this study is to evaluate manometric factors influencing complete vs. incomplete bolus transit in patients referred for esophageal function testing. Methods Combined MII-EM studies from 150 consecutive patients referred to our laboratory were evaluated comparing results obtained with individual swallows. Manometric diagnoses included normal manometry (33%), ineffective esophageal motility (17%), achalasia (11%), distal esophageal spasm (11%), poorly relaxing LES (11%), nutcracker esophagus (10%), hypertensive LES (5%), hypotensive LES (2%) Results The 150 patients described above completed a total of 1464 liquid swallows, characterized by MII as having complete or incomplete bolus transit. Data are presented in the table below according to manometric characteristics of indivadna[ swallow. Summary Incomplete bolus transit is associated with lower contraction amplitudes in the distal part of the esophagus. Manometric ineffective swallows with incomplete bolus transit had higher LES residual pressure compared to those with complete bolus transit. Conclusion These results suggest that contraction amplitude in the distal esophagus is the major determinant of bolus transit. Esophageal function testing using combined MII-EM helps clarify the interaction between esophageal body and 1-ES that enables bolus transit V prwsure tOcm~ve LES Pres=ure 5cmabo~ LES D~tal esophil ampltude LESP.N~ t~l Prmemrl
~rtT~ pedshd~ iniithlCtlv4 p~lalld II r p-vitue IncomplVe ~ p-v~=e
~
~
conb'actl~ll complet, p-vllue
988 , 165
1143 ' 21
0.294
184 07
255 14
0.001
598 6.3
1280 9.3
821 ' 114
1281 22
0003
219 ' 12
515 40
0001
62.2 - 82
157.3 . 11.8 0001
90.5 ' 117
1212 20
0.026
203 ~08
39.2 20
0001
610"67
1427 10.0 0.001
0.738
8107
47 0.4
0001
5607
62 11
5801
?7 1.0
#ofpalnepisodes # o f pain f T e e d a y t J 2 w k s Intensity of pain
Theophylline
2 0 { 13) 5(,4) 3(1)
1 2 ( 12)'1 7(, 5)'1" 2.5(:1.4)*
Natural History of Primary Eosinophilic Esophagitis: A Follow-Up of 30 Adult Patients for up to 12 Years Alex Straumann, Hans-Peter Spichtin, Hans-Uwe Simon, Mauro Pirovino, Christoph Beglinger
0001
Primary eosmophilic esophagitis (PEE) is an increasingly recognized, IL-5 driven inflammatory disorder of the esophagus. The only presenting symptom m adults is uniform attacks of dysphagia. PEE is histologically characterized by a dense infiltration of the esophageal epithelium with eosinophils. To date, the natural course of PEE has not been defined, and information regarding its potential long-term naks is still lacking. To our knowledge, this study is the first characterizing the natural course of PEE. Thirty adult patients (22 males and 8 females; mean age 40.6 years) with previously confirmed PEE were included in this study. The criteria for inclusion were: 1. typical history; 2. infiltration of the esophageal epithelium with > 24 eosinophils/hpf at the baseline examination; 3. time span > 1 year since diagnosis. GERD was excluded clinically, endoscopically and by 24-hour pH probe monitoring. After a mean follow-up time of 6.2 years (range 1.4 - 11.5), all patients underwent a foflow-up examination, consisting of a structured interview, physical examination, hematological and blood chemical analysis, determination of lymphocyte subpopulations in blood and EGD with histological examination of the esophageal, gastric and duodenal mucosa. All patients survived the study period and remained in good health. The dysphagia persisted in 28 patients and had, m 1 patient a major, and in 15, a minor negative impact on socioprofessional activities. Patients with blood eosinophiha had significantly more dysphagia attacks. The nutritional state remained stable (BMI 23.5 vs. 24.6; serum albumin 45.5 vs. 44.2). The eosinophilic infiltration of the esophagus persisted in all symptomatic patients, but the cell number decreased significantly (78.7 vs. 40.3 cells/hpi). The inflammatory process did not spread to the stomach or duodenum, but did evoke fibrosis of the esophageal lamina propria. Dysplasias or malignant esophageal conditions were not detected either endoscopically or histologically, and no lympho-proliferative diseases occurred. Based on this long-term observation of 30 adult patients, we conclude that PEE is almost always a primary-chronic disease, restricted to the esophagus It leads to persistent dysphagia and structural alterations of the esophageal tissue, but does not have an impact on the nutritional state. Furthermore, no disabling or malignant potential has been associated with this disease.
0138
Effects of Baclofen on Postprandial Fundic Tone and Lower Esophageal Sphincter Function in Man Kwang-Jae Lee, Rita Vos, Jozef Janssens, Jan Tack Background: The GABAB agonist baclofen was shown to inhibit transient lower esophageal sphincter relaxations (TLESRs) and to increase postprandial LES pressure in health and in reflux disease. Meal-induced increases in fundic volume trigger the reflex pathway underlying TLESRs, but the effect of baclofen on gastric meal accommodation is unknown. The aim of the study was to assess the effect of baclofen on postprandial fundic tone and LES function in man. Methods: Studies were performed in 7 healthy subjects (4 males: mean age 28 + 2 D's). After an overnight fast, a barostat bag was placed into the gastric fundus and a sleeve manometry catheter with pH electrode was positioned in the esophagus. With the harostat at MDP + 2 mmHg, recordings of fundic tone, esophageal manometry and esophageal pI-I were performed for 3.5 hours after oral ingestion of 40 mg baclofen or placebo in a randomized, double-blind manner. After 90 min, subjects ingested a liquid meal (200 mL, 300 kcal) Results: Ihe number of TLESP,s increased from 0.6_+0.3/h during fasting to 3.1_+ 0.5 and 2.1-+0.5/h during 1st and 2nd postprandial hour, respectively (p<0.05). Baclofen significantly reduced TLESR rate during 1st and 2nd postprandial hour (respectively, 0.6 -+ 0.3/h and 0 4 -+ 03/h; p
Abstracts
Placebo
17(14) 5(4) 3.3(,0.9)
874
872
AGA
Baseline
875 Plasma Ghrelin following Cure of Helicobacter pylori Dennis A. Freshwater, Paul O'Hare, Harpal S. Randeva, Chuka U Nwokohi Background: In the western world, the incidence of oesophageal adenocarcinoma has increased over the last 30 years coinciding with a decrease in the prevalence of Helicobacter pylori. Trends of increasing oesophageal adenocarcinoma can be linked causally to increasing gastroesophageal reflux disease (GORD) which can be linked to an increasingly obese population. However there is no plausible biological mechanism of association between Helicobacter pylori, obesity and GORD. Ghrelin, a peptide produced in the stomach, which regulates appetite, food intake and body composition as studied in Heflcobacter pylori positive asymptomatic subjects. Methods: Plasma ghrelin, leptin and gastrin were measured for 6 hours after an overnight fast, before and after cure of Helicohacter pylon in ten subjects. Twenty-four hour intragastric acidity was also assessed. Results: After cure median (95%
A-122