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Can clinical features predict erosive gastroesophageal reflux disease?
April 2000
1998), the acetic acid-induced rat gastric mucosal injury and Hp-infected Mongolian gerbil fundic mucosa, while its clinical relevance is still unclear. Aim: The present study was undertaken to elucidate the morphological and histochemical alteration of the myofibroblasts and microcirculatory units by the administration ofHp to the Mongolian gerbils. In addition, the expression of cyclooxygenase-2 (COX-2), a possible molecular target of carcinogenesis, was examined. Methods: Hp infection was induced by the oral administration of CagA and VacA positive Hp strain (ATCC43504) one, two, three and six months before the experiments. The localization of Hp, myofibroblasts and endothelial cells and COX-2 protein in the fundic and antral mucosa was investigated by the indirect immunofluorescence method using monoclonal antibodies and confocal laser microscopy (Zeiss LSM41O). The alteration of vascular permeability was clarified by the intraaortic infusion of FITC-dextran of several molecular sizes. Results: The number and size of the myofibroblasts significantly increased in the gastric mucosa three and six months after the Hp infection, especially in the area showing hyperplastic changes, but slightly near the erosive lesion. By the electron microscopic observation, these cells occupied the lamina propria. The microcirculatory network was elogated in the tip portion of the gastric mucosa and the vascular permeability in this area was markedly elevated three months after the infection. Immunoreactive COX-2 was predominantly and strongly expressed in sub-epithelial interstitial cells, mostly coincided with the myofibroblasts. Conclusions: From these observations, Hp infection for 3 and 6 months was found to bring about the increased expression of COX-2 in the activated fibroblasts in the hyperplastic gastric mucosa, suggesting its relation to the inflammation and carcinogenesis, rather than ulcer formation.
5861 CAN CLINICAL FEATURES PREDICT EROSIVE GASTROESOPHAGEAL REFLUX DISEASE? Sanjay Nandurkar, Nicholas 1. Talley, Univ of Sydney, Penrith, Australia. Introduction: Although gastroesophageal reflux disease (GERD) is a highly prevalent condition, erosive disease per se is uncommon but may require more aggressive treatment, since complications such as strictures and Barrett's are associated with it. Heartburn symptoms are thought to be a poor guide for predicting underlying erosive disease. Identification of markers of erosive GERD would enable more effective use of endoscopy to target populations at higher risk, and appropriate empirical therapy for others. Predictive models may help to improve the clinical decision making process. Aim: To create a model that would positively predict erosive GERD prior to endoscopy. Methods: Patients were enrolled prior to endoscopy. Symptomatic GERD was defined by presence of heartburn and divided into (I) infrequent (heartburn ~ IIweek) and (2) frequent (> 11 week). Severity (mild, moderate, severe) and duration of heartburn was assessed. Demographic data were collected. Body mass index (BM!) was calculated from height & weight. Alcohol, coffee, smoking, aspirin, NSAID, antisecretory medication and antacid use was determined. Macroscopic esophagitis was graded as per LA Classification. Models were built by forward stepwise selection followed by backward elimination in stepwise logistic regression. Corresponding sets of sensitivity and specificity for various cut-off points were analyzed using receiver operated characteristic (ROC) curves. Proportion of the deviance explained by the model was then calculated. Results: 170 patients enrolled (mean age 52 yrs; 47% males). GERD symptoms present in 64% (n= 109): infrequent 28% (n=47) and frequent 36% (n=62). Erosive GERD detected in 35% (n=59). In multivariate regression analysis, severe GERD symptoms (OR 5.6 95%CI 1.1-2.1, p= 0.02), male gender (OR 2.8 95%CI 1.7-7.7, p< 0.001), higher body mass index (OR 1.99 95%CI 1.05-1.3, p= 0.002) & H2RA use (OR 6.5 95%CI 1.3-5.9, p= 0.01) were independently associated with erosive GERD. Using ROC, the optimal threshold for predicting erosive GERD was identified to be 0.4. At this cut-off, the sensitivity and specificity for the model was 63% & 74%, respectively. This model explained 18.8% of the deviance. Conclusions: We have created a predictive score model for determining erosive GERD that has reasonable sensitivity and specificity. The predictive validity of our model now needs to be tested in primary care.
5862 ACCURATE DIAGNOSIS OF HELICOBACTER PYLORI INFECTION BY STOOL ANTIGEN TEST AND SIX OTHER CURRENTLY AVAILABLE TESTS IN CHILDREN. Yen-Hsuan Ni, Jaw-Town Lin, Shiu-Feng Huang, Jyh-Chin Yang, MeiHwei Chang, National Taiwan Univ Hosp, Taipei, Taiwan. Diagnosis of Helicobacter pylori (H. pylori) infection is crucial because of its association with gastritis, peptic ulcer, and gastric malignancy. Invasive and noninvasive tests have been developed for the diagnosis of H. pylori infection. Since H. pylori infection is mostly acquired in childhood and adolescence, accurate diagnosis of the infection in the pediatric population is important. The noninvasive diagnostic methods are particularly feasible
AGAA1283
in children. We conducted a study to compare the invasive tests: culture, biopsy urease test (BUT), histology, and polymerase chain reaction (PCR) on gastric biopsy specimens, with noninvasive tests: serology, l3C-urea breath test ( 13C-UBT), and a new diagnostic modality: stool antigen test (SA) to diagnose H. pylori infection in children. A total of 53 symptomatic children were enrolled into this study and all had completed the seven diagnostic tests for H. pylori. Our results showed all the diagnostic tests except serology were excellent methods of diagnosing H. pylori infection in children. The diagnostic accuracy of the seven tests were as follows: stool antigen test 96.2%; BUT 96.2%; histology 98.1%; PCR 94.3%; culture 98.1%; 13C-UBT 100%; and serology 84.9%. (Table)Stool antigen test, being highly sensitive and specific as shown in our data, will be potentially very helpful in diagnosing H. pylori infection in children when endoscopy and/or UBT is not applicable. Sensitivity, specificity, and diagnostic accuracy ofseven diagnostic tests forH. pylori infection in children
Sensitivity Specificity PPV NPV Accuracy
BUT
Histology
PCR
Culture
13C·UBT
IgG
SA
92.6% 100% 100% 92.9% 96.2%
96.3% 100% 100% 96.1% 98.1%
92.6% 96.2% 96.2% 92.6% 94.3%
96.3% 100% 100% 96.1% 98.1%
100% 100% 100% 100% 100%
88.9% 80.8% 82.8% 87.5% 84.9%
92.6% 100% 100% 92.9% 96.2%
PPV:posilive predictive value, NPV:negative predictive value
5863 MECHANISMS INVOLVED IN THE ATTENUATION OF INTESTINAL TOXICITY INDUCED BY S( + )KETOPROFEN IN REFED RAT. Ana Nieto, Virginia Motilva, Juan Manuel Herrerias, Frances Cabre, David Mauleon, Catalina Alarcon de la Lastra, Faculty of Pharmacy, Seville, Spain; Virgen Macarena Hosp, Seville, Spain; Menarini S A Lab, Barcelona, Spain. Background: In addition to suppression of PG synthesis, a number of factors have been implicated in NSAID enteropathy, including neutrophils and oxidative damage dependent vascular injuries, luminal bacteria, enterohepatic recirculation or feeding conditions. It has been suggested that inflammatory cytoquines, such as a- TNF, regulate endothelial adhesion molecules expression and promotes neutrophil adherence on vascular endothelial cells. Nitric oxide (NO) is a potent vasodilator than can maintain mucosal blood flow and inhibit neutrophil adherence counteracting the intestinal toxicity of NSAID. NO release activates soluble guanilate cyclase, increasing the levels of cGMP. Several NSAID, such as ketoprofen (KPF), are chiral drugs and therefore exist in two enantiomeric forms. Its therapeutic effects resides almost exclusively in the S( +) isomer, nevertheless the potential contribution to side effects cannot be ignored. Aim: to investigate the implications of neutrophils, a- TNF, luminal bacteria, and NO in the pathogenesis of intestinal injury induced by rac(:t )-ketoprofen vs its enantiomers using refed rats. Method: rats were fasted 24 hr before drug administration and refed 24 hr until sacrifice. Antibiotic prophylaxis was induced with amoxycillin (AMOX) given by gavage daily for two days before NSAID administration. Myeloperoxidase activity (MPO), index of neutrophil infiltration, was assessed spectrophotometrically. Mucosal intestinal production of cGMP and a-TNF was determined by a competitive immunoassay and an enzyme-linked immunoabsorbent assay respectively . Results. rae (:t)-KPF (100, 50, 25 mg/kg b.w.) dose-dependently caused longitudinal ulcers on the mesenteric side of the middle and distal intestine. Ulcerogenicity of S (+ )-ketoprofen was significantly reduced (p
1998), the acetic acid-induced rat gastric mucosal injury and Hp-infected Mongolian gerbil fundic mucosa, while its clinical relevance is still unclear. Aim: The present study was undertaken to elucidate the morphological and histochemical alteration of the myofibroblasts and microcirculatory units by the administration ofHp to the Mongolian gerbils. In addition, the expression of cyclooxygenase-2 (COX-2), a possible molecular target of carcinogenesis, was examined. Methods: Hp infection was induced by the oral administration of CagA and VacA positive Hp strain (ATCC43504) one, two, three and six months before the experiments. The localization of Hp, myofibroblasts and endothelial cells and COX-2 protein in the fundic and antral mucosa was investigated by the indirect immunofluorescence method using monoclonal antibodies and confocal laser microscopy (Zeiss LSM41O). The alteration of vascular permeability was clarified by the intraaortic infusion of FITC-dextran of several molecular sizes. Results: The number and size of the myofibroblasts significantly increased in the gastric mucosa three and six months after the Hp infection, especially in the area showing hyperplastic changes, but slightly near the erosive lesion. By the electron microscopic observation, these cells occupied the lamina propria. The microcirculatory network was elogated in the tip portion of the gastric mucosa and the vascular permeability in this area was markedly elevated three months after the infection. Immunoreactive COX-2 was predominantly and strongly expressed in sub-epithelial interstitial cells, mostly coincided with the myofibroblasts. Conclusions: From these observations, Hp infection for 3 and 6 months was found to bring about the increased expression of COX-2 in the activated fibroblasts in the hyperplastic gastric mucosa, suggesting its relation to the inflammation and carcinogenesis, rather than ulcer formation.
5861 CAN CLINICAL FEATURES PREDICT EROSIVE GASTROESOPHAGEAL REFLUX DISEASE? Sanjay Nandurkar, Nicholas 1. Talley, Univ of Sydney, Penrith, Australia. Introduction: Although gastroesophageal reflux disease (GERD) is a highly prevalent condition, erosive disease per se is uncommon but may require more aggressive treatment, since complications such as strictures and Barrett's are associated with it. Heartburn symptoms are thought to be a poor guide for predicting underlying erosive disease. Identification of markers of erosive GERD would enable more effective use of endoscopy to target populations at higher risk, and appropriate empirical therapy for others. Predictive models may help to improve the clinical decision making process. Aim: To create a model that would positively predict erosive GERD prior to endoscopy. Methods: Patients were enrolled prior to endoscopy. Symptomatic GERD was defined by presence of heartburn and divided into (I) infrequent (heartburn ~ IIweek) and (2) frequent (> 11 week). Severity (mild, moderate, severe) and duration of heartburn was assessed. Demographic data were collected. Body mass index (BM!) was calculated from height & weight. Alcohol, coffee, smoking, aspirin, NSAID, antisecretory medication and antacid use was determined. Macroscopic esophagitis was graded as per LA Classification. Models were built by forward stepwise selection followed by backward elimination in stepwise logistic regression. Corresponding sets of sensitivity and specificity for various cut-off points were analyzed using receiver operated characteristic (ROC) curves. Proportion of the deviance explained by the model was then calculated. Results: 170 patients enrolled (mean age 52 yrs; 47% males). GERD symptoms present in 64% (n= 109): infrequent 28% (n=47) and frequent 36% (n=62). Erosive GERD detected in 35% (n=59). In multivariate regression analysis, severe GERD symptoms (OR 5.6 95%CI 1.1-2.1, p= 0.02), male gender (OR 2.8 95%CI 1.7-7.7, p< 0.001), higher body mass index (OR 1.99 95%CI 1.05-1.3, p= 0.002) & H2RA use (OR 6.5 95%CI 1.3-5.9, p= 0.01) were independently associated with erosive GERD. Using ROC, the optimal threshold for predicting erosive GERD was identified to be 0.4. At this cut-off, the sensitivity and specificity for the model was 63% & 74%, respectively. This model explained 18.8% of the deviance. Conclusions: We have created a predictive score model for determining erosive GERD that has reasonable sensitivity and specificity. The predictive validity of our model now needs to be tested in primary care.
5862 ACCURATE DIAGNOSIS OF HELICOBACTER PYLORI INFECTION BY STOOL ANTIGEN TEST AND SIX OTHER CURRENTLY AVAILABLE TESTS IN CHILDREN. Yen-Hsuan Ni, Jaw-Town Lin, Shiu-Feng Huang, Jyh-Chin Yang, MeiHwei Chang, National Taiwan Univ Hosp, Taipei, Taiwan. Diagnosis of Helicobacter pylori (H. pylori) infection is crucial because of its association with gastritis, peptic ulcer, and gastric malignancy. Invasive and noninvasive tests have been developed for the diagnosis of H. pylori infection. Since H. pylori infection is mostly acquired in childhood and adolescence, accurate diagnosis of the infection in the pediatric population is important. The noninvasive diagnostic methods are particularly feasible
AGAA1283
in children. We conducted a study to compare the invasive tests: culture, biopsy urease test (BUT), histology, and polymerase chain reaction (PCR) on gastric biopsy specimens, with noninvasive tests: serology, l3C-urea breath test ( 13C-UBT), and a new diagnostic modality: stool antigen test (SA) to diagnose H. pylori infection in children. A total of 53 symptomatic children were enrolled into this study and all had completed the seven diagnostic tests for H. pylori. Our results showed all the diagnostic tests except serology were excellent methods of diagnosing H. pylori infection in children. The diagnostic accuracy of the seven tests were as follows: stool antigen test 96.2%; BUT 96.2%; histology 98.1%; PCR 94.3%; culture 98.1%; 13C-UBT 100%; and serology 84.9%. (Table)Stool antigen test, being highly sensitive and specific as shown in our data, will be potentially very helpful in diagnosing H. pylori infection in children when endoscopy and/or UBT is not applicable. Sensitivity, specificity, and diagnostic accuracy ofseven diagnostic tests forH. pylori infection in children
Sensitivity Specificity PPV NPV Accuracy
BUT
Histology
PCR
Culture
13C·UBT
IgG
SA
92.6% 100% 100% 92.9% 96.2%
96.3% 100% 100% 96.1% 98.1%
92.6% 96.2% 96.2% 92.6% 94.3%
96.3% 100% 100% 96.1% 98.1%
100% 100% 100% 100% 100%
88.9% 80.8% 82.8% 87.5% 84.9%
92.6% 100% 100% 92.9% 96.2%
PPV:posilive predictive value, NPV:negative predictive value
5863 MECHANISMS INVOLVED IN THE ATTENUATION OF INTESTINAL TOXICITY INDUCED BY S( + )KETOPROFEN IN REFED RAT. Ana Nieto, Virginia Motilva, Juan Manuel Herrerias, Frances Cabre, David Mauleon, Catalina Alarcon de la Lastra, Faculty of Pharmacy, Seville, Spain; Virgen Macarena Hosp, Seville, Spain; Menarini S A Lab, Barcelona, Spain. Background: In addition to suppression of PG synthesis, a number of factors have been implicated in NSAID enteropathy, including neutrophils and oxidative damage dependent vascular injuries, luminal bacteria, enterohepatic recirculation or feeding conditions. It has been suggested that inflammatory cytoquines, such as a- TNF, regulate endothelial adhesion molecules expression and promotes neutrophil adherence on vascular endothelial cells. Nitric oxide (NO) is a potent vasodilator than can maintain mucosal blood flow and inhibit neutrophil adherence counteracting the intestinal toxicity of NSAID. NO release activates soluble guanilate cyclase, increasing the levels of cGMP. Several NSAID, such as ketoprofen (KPF), are chiral drugs and therefore exist in two enantiomeric forms. Its therapeutic effects resides almost exclusively in the S( +) isomer, nevertheless the potential contribution to side effects cannot be ignored. Aim: to investigate the implications of neutrophils, a- TNF, luminal bacteria, and NO in the pathogenesis of intestinal injury induced by rac(:t )-ketoprofen vs its enantiomers using refed rats. Method: rats were fasted 24 hr before drug administration and refed 24 hr until sacrifice. Antibiotic prophylaxis was induced with amoxycillin (AMOX) given by gavage daily for two days before NSAID administration. Myeloperoxidase activity (MPO), index of neutrophil infiltration, was assessed spectrophotometrically. Mucosal intestinal production of cGMP and a-TNF was determined by a competitive immunoassay and an enzyme-linked immunoabsorbent assay respectively . Results. rae (:t)-KPF (100, 50, 25 mg/kg b.w.) dose-dependently caused longitudinal ulcers on the mesenteric side of the middle and distal intestine. Ulcerogenicity of S (+ )-ketoprofen was significantly reduced (p