ERD Patients Research Articles

#1861 Association of the polymorphisms of the angiotensin converting enzyme and FRMD3 genes in the development of diabetic kidney disease

Abstract Background and Aims Individual genetic biomarkers, called single nucleotide polymorphisms (SNPs), have been proposed that could represent potential non-invasive markers for the early diagnosis of diabetic kidney disease (DKD), in addition to their association with a characteristic phenotype. Aim To determine the association of polymorphisms of the Angiotensin Converting Enzyme and FRMD3 genes with the risk of developing ERD in patients with type 2 diabetes. Method Case-control study, comparative, observational, ambispective and cross-sectional, in which men and women, over 18 years of age with T2D with and without ERD and healthy patients, who underwent DNA extraction, participated. genomic and subsequent genotyping, and detection of SNPs by mass spectrometry. Results A total of 400 patients participated, 199 men and 201 women, within which they were divided into three groups: 100 patients with type 2 diabetes and ERD confirmed by renal biopsy, 100 patients with type 2 diabetes without ERD and 200 healthy controls. A total of 3 polymorphisms of the ACE and FRMD3 genes were studied. Among the polymorphisms analyzed in the logistic regression, rs179975 CA (OR, 6.2; 95% CI: 1.15-7.48, p = 0.03), rs1888747 GA (OR, 6.6; 95% CI: 4.60-8.45, p = 0.002) and rs10868025 resulted. CG (OR, 4.1; 95% CI: 2.40-5.60, p = 0.002) Table 1. Conclusion Our study demonstrated the association of well-established genetic variants of the ACE and FRMD3 gene polymorphisms with the presence of ERD, showing that these SNPs, specifically rs179975 CA, rs1888747 GA and rs10868025 GC, may represent important genetic markers in the development of ERD and could be a predisposing factor due to the high frequency and strength of association that were observed in our studied population, this being the first study in Latin America.

Efficacy of Alginate-Antacid Medication in the Treatment of Patients with Gastroesophageal Reflux Disease

Efficacy of Alginate-Antacid Medication in the Treatment of Patients with Gastroesophageal Reflux Disease

Gender is a risk factor in patients with gastroesophageal reflux disease.

Background: Prevalence of gastroesophageal reflux disease (GERD) has increased in the last decades, and it is now one of the most common chronic and recurrent diseases. The present study aimed at determining the frequency of gender (sex) and age in Iranian patients with GERD symptoms. Methods: In this study, 803 patients aged 11 to 84 years, with erosive and nonerosive gastroesophageal reflux diseases, based on the questionnaire and esophagogastroduodenoscopy findings, participated. The female group was compared with the male group with respect to age, symptoms, esophageal injury, and hiatus hernia. Results: Of the 803 participants, 60.5% (n= 486) were female, and 69.2% (n= 555) were younger than 50 years. Of those patients older than 50 years, 32.8% (n= 81) were female. Moreover, 31.0% (n= 249) of the patients had erosive esophagitis (ERD), and 69.0% (n= 254) had normal esophageal mucosa (NERD).The female to male ratio was 1/1.06 and 1.94/1 in ERD and NERD patients, respectively. Hiatal hernia was more prevalent in females than in males. Conclusion: Nonerosive reflux disease, as a gastroesophageal reflux disease (GERD), was more common in females than in males. GERD became more prevalent with increase in age. Gender and hiatal hernias were 2 potential risk factors of GERD.

Su2100 Differences in Resting State Functional Connectivity of Interoceptive and Default Mode Networks in Nerd and Healthy Controls

these significant differences, NERD and ERD groups showed substantial classification with superior classification in the buffer (figure 1C) compared to the acid condition (figure 1D). Conclusions: Interoceptive network functional connectivity responds differently to acid and buffer induced esophageal stimulation in NERD and ERD patients. These differences can be exploited to classify these two groups from each other and from healthy controls.

Su2102 Objective Diagnosis of Minimal Hepatic Encephalopathy (MHE) by Analysis of Brain Resting State Functional Connectivity

these significant differences, NERD and ERD groups showed substantial classification with superior classification in the buffer (figure 1C) compared to the acid condition (figure 1D). Conclusions: Interoceptive network functional connectivity responds differently to acid and buffer induced esophageal stimulation in NERD and ERD patients. These differences can be exploited to classify these two groups from each other and from healthy controls.

Failure to respond to physiologic challenge characterizes esophageal motility in erosive gastro-esophageal reflux disease

Non-specific esophageal dysmotility with impaired clearance is often present in patients with gastro-esophageal reflux disease (GERD), especially those with erosive disease; however the physio-mechanic basis of esophageal dysfunction is not well defined. Retrospective assessment of patients with erosive reflux disease (ERD; n=20) and endoscopy negative reflux disease (ENRD; n=20) with pathologic acid exposure on pH studies (>4.2% time/24 h) and also healthy controls (n=20) studied by high resolution manometry. Esophageal motility in response to liquid and solid bolus swallows and multiple water swallows (MWS) was analyzed. Peristaltic dysfunction was defined as failed peristalsis, spasm, weak or poorly coordinated esophageal contraction (>3cm break in 30 mmHg isocontour). Peristaltic dysfunction was present in 33% of water swallows in controls, 56% ENRD and 76% ERD respectively (P<0.023 vs controls, P=0.185 vs ENRD). The proportion of effective peristaltic contractions improved with solid compared to liquid bolus in controls (18%vs 33%, P=0.082) and ENRD (22%vs 54%, P=0.046) but not ERD (62%vs 76%, P=0.438). Similarly, MWS was followed by effective peristalsis in 83% of controls and 70% ENRD but only 30% ERD patients (P<0.017 vs controls and P<0.031 vs ENRD). The association between acid exposure and dysmotility was closer for solid than liquid swallows (r=0.52 vs 0.27). Peristaltic dysfunction is common in GERD. ERD patients are characterized by a failure to respond to the physiologic challenge of solid bolus and MWS that is likely also to impair clearance following reflux events and increase exposure to gastric refluxate.

Intercellular Space Volume Is Mainly Increased in the Basal Layer of Esophageal Squamous Epithelium in Patients with GERD

At present, the dilation of esophageal intercellular spaces (ICS) is considered an early morphologic marker of acid damage in patients with GERD. Nevertheless, previous electron microscopic (EM) studies had focused only on the suprabasal layer of squamous epithelium or did not nearly specify which layer of squamous epithelium was studied. Therefore, we aimed to assess the volumetric amount of the ICS in all layers of SE in patients with GERD. In this study, 48 patients were prospectively included (NERD = 18, ERD = 17; Barrett's esophagus = 5, controls = 8). All patients with ERD and NERD had typical reflux symptoms, as assessed by a valid GERD questionnaire. ICS volume was assessed by electron microscopy in the superficial, prickle cell, and basal layers of esophageal squamous epithelium using the method of Weibel. ERD was associated with increased ICS volume in the basal layer (LA-A, p = 0.038; LA-B, p = 0.005) and prickle cell layer (LA-A, p = 0.006; LA-B, p = 0.007) as compared to controls. Comparisons between NERD and ERD patients revealed more dilated ICS in the basal layer (LA-B, p = 0.007), prickle cell layer (LA-A, p = 0.008; LA-B, p = 0.001) and superficial layer (LA-B, p = 0.018) in patients with ERD. Not only the diameter but also the volume of the ICS is increased in patients with GERD. Furthermore, the dilation of ICS is present in all three layers of the SE, being more pronounced in the basal layer. These findings support the concept that the impairment of the esophagus begins in the deeper parts of the esophageal epithelium.

Potential role of the cannabinoid receptor CB1 in the pathogenesis of erosive and non‐erosive gastro‐oesophageal reflux disease

Cannabinoid (CB) receptors have been located in brain areas involved in the triggering of TLESRs as well as in the nodose ganglion from which vagal afferents emanate. The distribution of CB(1) receptors has been investigated in the human gastrointestinal mucosa, as expression of inflammatory process. To evaluate the CB(1) expression in oesophageal mucosa. A total of 87 consecutive subjects were enrolled: 10 controls, 39 NERD and 38 erosive oesophagitis. Eight specimens were taken from macroscopically normal mucosa. Five were processed by haematoxylin-eosin, MIB1/CB(1) evaluation and three for the RNA and proteins extraction. The mean MIB1-LI value was 31% and 22% in NERD and ERD patients, respectively, compared to 68% in the healthy subjects. Mean CB(1)mRNA/GUSB mRNA value of the controls was 0.66, while in GERD patients, it was 0.28. In NERD and ERD, the mean values of CB(1)/GUSB were 0.38 and 0.17, respectively, with highly significant differences between the NERD vs. ERD groups. Semi-quantitative analysis of CB(1) expression, performed with WB, shows in NERD patients a higher CB(1) receptor expression than ERD patients. With this study, we showed for the first time the presence of CB(1) receptors in the human oesophageal epithelium.

S1908 Symptom Association Probability for Acid and Nonacid Reflux in Patients with Erosive Esophagitis (EE) and Non-Erosive Reflux Disease (NERD)

s / Digestive and Liver Disease 42S (2010) S61–S192 S109 the RNA extraction for real-time PCR analysis or until protein extraction for WB examination. Results: Immunocytochemical staining shows the presence of CB1 receptor in esophageal mucosa of both control and GERD patients. Semi-quantitative analysis, performed with WB, shows a differential expression of CB1 with the higher expression (40%) in NERD respect to ERD. Real-time analysis shows a decrease of CB1 receptor RNA in normal esophagus respect to colon, taken as positive control, of about 30%. NERD show lover levels of CB1 compared with colon (-62%) and 2 fold higher respect to ERD mucosa. The results are the mean ± SEM of three independent experiments. Mean expression of CB1 in NERD mucosa is higher, but show elevated variability between patients, with respect to ERD mucosa. Conclusions: Immunocytochemical staining, real-time PCR and WB analyses confirm that CB1 receptor is expressed in human esophageal epithelium. In ERD and NERD patients, the expression of CB1 is increased, compared to control. Expression of CB1 in NERD is higher than ERD. These findings confirm that CB1 receptors are also involved in the esophageal mucosal defense mechanism. # A. Oesophagus 1. GERD

Esophageal cell proliferation in gastroesophageal reflux disease: Clinical-morphological data before and after pantoprazole

To evaluate esophageal mucosal defense mechanisms at an epithelial level to establish if pantoprazole treatment can induce ultrastructural healing and improvement in the proliferation activity of the esophageal epithelium in gastroesophageal reflux disease (GERD). This was a single-blinded study for pH-monitoring, and histological, ultrastructural and MIB1 immunostaining evaluation. Fifty eight patients with GERD were enrolled and underwent 24 h pH-monitoring and endoscopy. Patients were treated for 12 and 24 mo with pantoprazole. Esophageal specimens were taken for histological and ultrastructural evaluation, before and after the treatment. With transmission electron microscopy, all patients with GERD showed ultrastructural signs of damage with dilation of intercellular spaces (DIS). After 3 mo of therapy the mean DIS values showed a significant reduction and the mean MIB1-LI values of GERD showed an increase in cell proliferation. A further 3 mo of therapy significantly increased cell proliferation only in the erosive esophagitis (ERD) group. Three months of pantoprazole therapy induced ultrastructural healing of mucosal damage in 89% and 93% of ERD and non-erosion patients, respectively. Moreover, long-term pantoprazole treatment may be helpful in increasing the capability for esophageal cell proliferation in GERD, particularly in ERD patients.

Prevalence ofHelicobacter pyloriand cytotoxin-associated gene a in iranian patients with non-erosive and erosive reflux disease

The prevalence of Helicobacter pylori (H. pylori) infection and its virulent strain (cytotoxin-associated gene A: CagA) has not been evaluated in patients with gastroesophageal reflux disease (GERD) subgroups (erosive and non-erosive) in Iran. This study was conducted to evaluate H. pylori infection and anti-CagA status in GERD. One hundred fifty-four patients (71 male and 83 female; mean age, 42.6+/- 15.5 years) were evaluated for symptoms--heartburn and acid regurgitation--compatible with GERD. The esophagus was diagnosed endoscopically whether it was with erosion (erosive reflux disease, ERD) or without erosion (non-erosive reflux disease, NERD). Rates of anti-H. pylori and anti-CagA-IgG (immunoglobulin G) antibodies were determined for each subject by ELISA. H. pylori was considered by ELISA if the rapid urease test proved positive. anti-H. pylori and anti-CagA statuses were compared in ERD and NERD patients with and without related IgG antibodies. Mean values and P values were calculated using SPSS (version 12). The overall prevalence of H. pylori infection was 75.3% (116/154). Anti-CagA antibody was found in 60.3% (70/116) of infected patients. The prevalence of H. pylori infection in patients with NERD and ERD was 81.2% (56/69) and 70.6% (60/85), respectively (OR=0.56; 95% CI [confidence interval]=0.26-1.20; P=.14). The prevalence of anti-CagA antibody in infected NERD and ERD patients was 58.9% (33/56) and 61.7% (37/60), respectively (OR=1.16; 95% CI=0.49-1.70; P=0.83). The results showed that more than 70% of the patients, either NERD or ERD, acquire H. pylori infection. Anti-CagA antibody is also common in patients with reflux disorders in our community.

NERD, GERD, and Barrett’s Esophagus: Role of Acid and Non-acid Reflux Revisited with Combined pH-Impedance Monitoring

Gastroesophageal reflux is the most important factor in the development of Barrett's metaplasia. The effect of acid reflux is commonly accepted today, but there is controversy about the role of non-acid reflux. With introduction of combined esophageal pH-impedance monitoring, a precise diagnostic test for acid and non-acid reflux is now available. Ninety two consecutive patients (33 women) off acid-suppressive therapy underwent diagnostic work-up for suspected gastroesophageal reflux disease including upper-GI endoscopy, esophageal manometry, barium swallow, and combined esophageal pH-impedance monitoring. Patients were subdivided into three groups according to symptoms and endoscopic appearance: typical symptoms without esophagitis (n = 28; NERD); erosive esophagitis (n = 52, ERD), and patients with intestinal metaplasia (n = 12, BE). Pathologic acid reflux during pH-metry was found in 35.7%, 63.5%, and 75.0% for NERD, ERD, and BE patients, respectively (P = 0.022). Likewise, the percentage of time pH < 4 rose significantly during upright, supine, and total phases. In contrast, combined pH-impedance monitoring showed no significant difference between groups for the number of acid reflux events and for percentage of acid bolus reflux time. However, BE patients had significantly more non-acid reflux events and a higher percentage of non-acid bolus reflux time during the supine (P = 0.043, P = 0.020, respectively), but not during the upright phase (P = 0.740, P = 0.730, respectively). Patients with BE are exposed to increased supine non-acid reflux and to increased acid reflux during upright and supine phases. This observation supports the concept that nocturnal non-acid reflux may play a role in the pathogenesis of BE.

Non-erosive and erosive gastroesophageal reflux diseases: No difference with regard to reflux pattern and motility abnormalities

Objective. To investigate whether gastroesophageal reflux disease (GERD) with mild to moderate erosive esophagitis (ERD) is a more severe disease regarding the amount of acid reflux, motor abnormalities, and the presence/absence of hiatus hernia than non-erosive reflux disease (NERD). Material and methods. The study comprised a retrospective analysis of prospectively collected data on 313 consecutive subjects referred for endoscopy, pH-metry, and esophageal manometry. The patients were divided into four groups: Group I (n=92), subjects without GERD with normal pH-metry, without esophagitis and without reflux symptoms; Group II (n=111), patients with NERD (no esophagitis, abnormal pH-metry); Group III (n=77), patients with mild to moderate ERD (LA A, B; abnormal pH-metry); Group IV (n=33), patients with severe or complicated esophagitis (LA C, D; Barrett's esophagus). All data are expressed as medians with 5th–95th percentiles. Results. No difference was found in the amount of acid reflux between patients with mild to moderate ERD and those with NERD. The DeMeester score was 34.5 (17–105) in NERD patients and 31.6 (15–102) in ERD patients. No significant differences were found between NERD and ERD patients regarding lower esophageal sphincter (LES) basal pressure (11.6 mmHg; 3–25 in NERD versus 10.7 mmHg; 3–22 in ERD). Similar proportions of patients with NERD and ERD had low LES basal pressure (20.7% in NERD versus 24.7% in ERD; NS) and hiatus hernia (44% and 56%; NS). A relatively high proportion of patients without GERD (Group I) had ineffective esophageal motility (39%) and hiatus hernia (30%). Conclusions. No difference was found between NERD and mild to moderate ERD in terms of acid exposure time and esophageal motor abnormalities. To a certain extent, ERD is a “more complicated” form of the disease. Host factors related to a particular patient (e.g. mucosal defense, genetics, acid clearance) might be responsible for the development of esophagitis.