Nocturnal acid breakthrough - approach to management

Nocturnal acid breakthrough is defined as the presence of intragastric pH < 4 during the overnight period for at least 60 continuous minutes in patients taking a proton-pump inhibitor (PPI). Nocturnal acid breakthrough occurs in more than 70% of Helicobacter pylori-negative patients on PPI therapy and has clinical consequences in particular in patients with complicated gastroesophageal reflux disease (GERD), Barrett's esophagus, and esophageal motility abnormalities. The clinical importance of nocturnal acid breakthrough and the benefit of adding histamine-2 receptor antagonists (H2RAs) to PPI therapy have been debated ever since these concepts were introduced. In our experience, the addition of bedtime H2RAs is clinically effective in controlling nocturnal acid breakthrough and GERD symptoms.     

Impaired ghrelin signaling is associated with gastrointestinal dysmotility in rats with gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is often associated with decreased upper gastrointestinal motility, and ghrelin is an appetite-stimulating hormone known to increase gastrointestinal motility. We investigated whether ghrelin signaling is impaired in rats with GERD and studied its involvement in upper gastrointestinal motility. GERD was induced surgically in Wistar rats. Rats were injected intravenously with ghrelin (3 nmol/rat), after which gastric emptying, food intake, gastroduodenal motility, and growth hormone (GH) release were investigated. Furthermore, plasma ghrelin levels and the expression of ghrelin-related genes in the stomach and hypothalamus were examined. In addition, we administered ghrelin to GERD rats treated with rikkunshito, a Kampo medicine, and examined its effects on gastroduodenal motility. GERD rats showed a considerable decrease in gastric emptying, food intake, and antral motility. Ghrelin administration significantly increased gastric emptying, food intake, and antral and duodenal motility in sham-operated rats, but not in GERD rats. The effect of ghrelin on GH release was also attenuated in GERD rats, which had significantly increased plasma ghrelin levels and expression of orexigenic neuropeptide Y/agouti-related peptide mRNA in the hypothalamus. The number of ghrelin-positive cells in the gastric body decreased in GERD rats, but the expression of gastric preproghrelin and GH secretagogue receptor mRNA was not affected. However, when ghrelin was exogenously administered to GERD rats treated with rikkunshito, a significant increase in antral motility was observed. These results suggest that gastrointestinal dysmotility is associated with impaired ghrelin signaling in GERD rats and that rikkunshito restores gastrointestinal motility by improving the ghrelin response.     

Medical therapy of gastroesophageal reflux disease in secondary and tertiary care settings

Gastroesophageal reflux disease (GERD) is common. Many patients with recurring or troublesome symptoms are referred for endoscopic examination. Patients seen in secondary care usually have failed OTC or primary care anti-reflux therapy. Acid suppression is the mainstay of healing and maintenance therapy. Increasingly proton pump inhibitors (PPIs) are preferred above H2 receptor antagonists (H2RAs), not only for the more severe end of the GERD spectrum but also for patients with mild degrees of esophagitis. Not all patients respond symptomatically to acid suppression, not even with high dose PPI. Prokinetics are mainly useful in the milder degrees of GERD. It is still not clear whether a particular symptom cluster can be recognized for which prokinetics are especially useful. The concept of "step-up versus step-down" approach remains in need for proper validation. Switching from PPIs to cisapride for "step-down" maintenance appears inadequate in practice. All current therapies have shortcomings; H2RAs insufficiently block meal-stimulated acid secretion; long-term strong acid suppression worsens Helicobacter pylori-associated inflammation in the corpus and may accelerate development of atrophy; PPI-potency is substantially weaker in non-H. pylori infected individuals. Optimization of individualized therapy will require more potent and more precisely targeted motility modulating drugs and superior acid/peptic inhibiting pharmaceuticals.     

胃食管反流病的治疗进展

胃食管反流病(gastroesophaeal reflux disease,GERD)是医疗实践中的最常见的疾病之一,其发病率在世界范围内呈逐年上升趋势,且随年龄增长而增加,40-60岁为高发年龄[1]。GERD是一种由胃、十二指肠内容物反流入食管引起不适症状和(或)并发症的疾病,GERD在临床上大致可分为:糜烂性食管炎(EE)(反流性食管炎(RE))和非糜烂性食管炎(NERD)。其中NERD最多见,约占60%。GERD远期危害较小,但其病情漫长且极易复发,严重影响了生活质量。主要表现为食管症状(包括典型的烧心和反流)和食管外症状(包括咽部异物感、咳嗽、声嘶、哮喘、咽喉炎等表现),还有增加发展为Barrett食管及食管癌的危险[2,3]。GERD的治疗目的是愈合食管炎,快速缓解症状、减少复发、提高生活质量,治疗方法主要包括以下4个方面:一般治疗,药物治疗,内镜下治疗和外科治疗。近年来已成为国内外研究的热点,本文就近年来对GERD的治疗进展做一综述。     

Esophageal tone in patients with total aperistalsis: gastroesophageal reflux disease versus achalasia

We have evaluated esophageal tone in two different conditions that, in some cases, similarly impair phasic esophageal motility. Studies were performed in 14 healthy volunteers, 10 patients with total esophageal aperistalsis secondary to gastroesophageal reflux disease (GERD), and 25 untreated achalasia patients. We quantified esophageal compliance and relaxation induced by a nitric oxide donor using a barostat. Intraesophageal volume at a minimal distending pressure (2 mmHg) was not significantly different among all three groups (4.1 +/- 0.7, 3.8 +/- 0.7, and 4.2 +/- 1.2 ml for healthy, GERD, and achalasia groups, respectively). Esophageal compliance was significantly increased (P < 0.05 vs. healthy group) in the two groups of patients with aperistalsis (1.9 +/- 0.2, 3.0 +/- 0.2, and 3.1 +/- 0.3 ml/mmHg for healthy, GERD, and achalasia groups, respectively). Esophageal relaxation was decreased in GERD patients (Delta diameter: 0.4 +/- 0.1 cm) and increased in achalasia patients (Delta diameter: 1.3 +/- 0.4 cm) relative to healthy subjects (Delta diameter: 0.9 +/- 0.2 cm) (P < 0.05 for GERD vs. achalasia and healthy groups). Our results indicate that diseases that similarly impair phasic esophageal motility may affect esophageal tone differently.     

Drugs, bugs, and esophageal pH profiles

Until relatively recently, gastroesophageal reflux disease (GERD) was thought to be a relatively trivial problem, and pharmaceutical companies initially had remarkably little interest in clinical trials for GERD. Over the last ten years, GERD therapy has become the subject of intense interest, since reflux disease is now recognized as a major market for antisecretory and prokinetic drugs. Even low-technology antacids are now known to effectively neutralize esophageal acid prevent acid reflux for up to 90 minutes. Esophageal pH profiling is known to be an excellent surrogate for clinical efficacy of GERD drugs, particularly in erosive esophagitis. Years ago, famotidine normalized esophageal mucosal exposure to pH < 4.0 only when administered in doses of 40 mg twice a day. Subsequent studies confirmed that multiple daily dosing of histamine-2 receptor antagonists (H2RAs) was mandatory for GERD treatment, with clear dose-response relationships for each agent. Proton pump inhibitors (PPIs) have each been carefully assessed in terms esophageal and gastric pH profiles. Omeprazole has a particularly flat dose response curve, making it difficult to differentiate pH or clinical effects of 20 vs. 40 mg doses. Improved rapidity of onset and/or enhanced potency is demonstrable in pH data obtained with lansoprazole, rabeprazole and pantoprazole. Such differences will translate to improved clinical efficacy, based on the meta-analyses of Richard Hunt and his group in Canada that correlate pH effects and symptom relief/healing. PPI's have dependably surpassed H2RAs and prokinetic drugs in management of the more severe grades of esophagitis. Helicobacter pylori has a peculiar relationship to GERD. There has been some concern that PPIs given to patients with H. pylori might accelerate development of severe atrophic gastritis. It is also now known that eradication of H. pylori may increase symptomatic GERD (possibly as a result of increased gastric acid secretion once the bacteria have been eliminated). New data confirm nocturnal breakthrough of acid secretion and esophageal acid exposure in three-fourths of patients on omeprazole 20 mg twice daily. This nocturnal acidity can be controlled more effectively with a nighttime dose of an H2RA than with a third dose of omeprazole. Control of acid secretion and improved gastric and esophageal pH profiles are goals of modern GERD therapy, and the product that most cost effectively normalizes esophageal acid exposure will have a substantial advantage in the ever-growing GERD marketplace.     

Current Advancement on the Dynamic Mechanism of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a common clinical disease associated with upper gastrointestinal motility disorders. Recently, with improvements in living standards and changes in lifestyle and dietary habits, the incidence of GERD has been increasing yearly. However, the mechanism of GERD has not been fully elucidated due to its complex pathogenesis, and this had led to unsatisfactory therapeutic outcomes. Currently, the occurrence and development of GERD involve multiple factors. Its pathogenesis is mainly thought to be related to factors, such as lower esophageal sphincter pressure, transient lower esophageal sphincter relaxation, crural diaphragmatic dysfunction, hiatus hernia, and impaired esophageal clearance. Therefore, explaining the pathogenesis of GERD more clearly and systematically, exploring potential and effective therapeutic targets, and choosing the best treatment methods have gradually become the focus of scholars'' attention. Herein, we reviewed current advancements in the dynamic mechanism of GERD to better counsel patients on possible treatment options.     

终末期肾病患者合并胃食管反流病的临床研究进展

胃食管反流病(GERD)是最常见的食管疾病之一。多项研究表明,终末期肾病(ERSD)患者GERD的患病率高于普通人群。目前对于ERSD患者特别是血液透析患者GERD的症状特点及严重程度的研究较少。ESRD患者常并发或伴发糖尿病、高血压等,而糖尿病神经病变可影响胃排空功能,钙拮抗剂和硝酸酯类药物可影响LES舒张功能。透析相关淀粉样变通过影响食管蠕动、食管下段括约肌张力和胃排空影响GERD的发生。ERSD患者中,相当比例的患者全身状况不佳,行胃镜风险较高,常常应用标准化量表或质子泵抑制剂诊断试验评估患者症状性GERD患病情况。ESRD及透析患者GERD的知晓率仍较低,部分患者自行服用碳酸氢钠等非一线药物控制症状。理论上对于ESRD及透析患者伴随的GERD进行早期诊断和治疗可能提高患者生活质量,并减少水钠摄入,改善血压及透析间期体重增加,降低心血管事件风险,具体的临床获益仍有待进一步研究证实。     

Bile-acid-induced calcium signaling in mouse esophageal epithelial cells

In patients with gastroesophageal reflux disease (GERD), esophageal exposure to both acid and duodenogastroesophageal reflux are more common than to acid reflux alone, suggesting that acidic bile acid in duodenal juice may contribute to the pathophysiology and severity of GERD. However, the mechanism whereby esophageal mucosal epithelial cells react to bile acid remains unclear. We visually examined the real-time response of mouse esophageal epithelial cells to bile acids using calcium (Ca²⁺)-imaging methods. We investigated the effects of seven different bile acids. After stimulation for a few minutes, only Deoxycholate (DCA) under acidic conditions caused a elevation of intracellular Ca²⁺ concentration ([Ca²⁺]_i)in the cells in dose- and pH-dependent manners. Conjugated bile acids had no effect on the cells. Viability assay of the cells in the presence of DCA was in good agreement with the calcium imaging data. Besides, DCA-induced [Ca²⁺]_i increase in acidic conditions was observed not only in isolated primary cultured cells, but also in cells in the stratified squamous epithelium. This study suggests that DCA can pass through the anatomical barrier of the esophageal epithelium and induce calcium signaling in epithelial cells in a pH-dependent manner. This supports the hypothesis that bile acid reflux together with gastric acid can affect the esophageal mucosa, even under reflux times of a few minutes.     

Value of heartburn for diagnosing gastroesophageal reflux disease in severely obese patients

Objective : To evaluate the prevalence of gastroesophageal reflux disease (GERD) in severely obese patients and the association between symptoms and objective data of GERD in this population. Research Methods and Procedures : A total of 158 consecutive severely obese patients (BMI ≥ 40 kg/m²) were prospectively evaluated. Symptoms were evaluated by a structured clinical questionnaire. Objective assessment was made by ambulatory 24‐hour esophageal pH monitoring and endoscopy. GERD was defined by the presence of symptoms or complications (esophagitis). The clinical criterion defining GERD was the presence of at least two episodes of heartburn per week. Results : The mean age of the 138 patients subjected to complete study was 42.6 ± 10.2 years, with a BMI of 50.1 ± 6.9 kg/m² (range, 40.6 to 69.4 kg/m²); 78% were women. The prevalence of GERD evaluated by symptoms and/or esophagitis was 33.3% (46/138). Clinical criteria of GERD were present in 31/138 cases (22.5%), and 26 (18.8%) had esophagitis. In 69/138 patients (50%), pHmetry was abnormal. Fifty‐three patients with esophagitis and/or abnormal pHmetry were asymptomatic. The sensitivity of heartburn as a diagnostic criterion of GERD in patients with severe obesity was 29.3%, with a specificity of 85.7%. No significant association was observed between severe obesity grade and the prevalence of symptoms and/or objective data. Discussion : Asymptomatic gastroesophageal reflux (abnormal esophageal acid exposure and/or reflux esophagitis) is more common than symptomatic gastroesophageal reflux in severely obese patients. Increased BMI is not associated with a greater prevalence of GERD in these patients.     

pH, healing rate, and symptom relief in patients with GERD

Gastroesophageal reflux symptoms are common and occur in all of us from time to time. In others, reflux may be associated with ulcerative esophagitis. The symptoms may be aggravated by large meals, coffee, smoking and position. Physiological and pathological reflux can be separated by the frequency and duration of the exposure of the lower esophagus to acid. Pathological reflux results in symptoms and also esophagitis and ulceration in some patients. Although gastroesophageal reflux disease (GERD) is considered to result from a disorder of motility in the esophagus, gastric acid and peptic activity are deemed pivotal to the initiation and continuation of the esophageal damage and the development of symptoms. Acid exposure in the esophagus is normally less than 4 percent of the 24 hours with a pH below 4. An increase over 4 percent of the time with a pH less than 4 is considered pathological. Hence, antisecretory drugs have become the principle approach to the treatment of reflux symptoms and esophagitis since they reduce the acidity, of gastric juice and the activity of pepsin. Importantly, they also reduce the volume of gastric juice available for reflux into the esophagus. There is a clear relationship between the degree and duration of acid suppression and the relief of heartburn and healing of esophagitis. Pharmacodynamic studies with different dose regimens of the H2-receptor antagonists and the proton pump inhibitors show a difference in the degree and duration of the antisecretory effect, and this correlates closely with the results of clinical trials with respect to the healing of esophagitis and the relief of symptoms. Proton pump inhibitors achieve healing rates by week four, which are not achieved by H2-receptor antagonists even after 12 weeks of treatment. The advantage of proton pump inhibitors over H2-receptor antagonists is due to the greater degree, longer duration of effect and more complete inhibition of acid secretion that maintains intragastric pH above 4 for a maximal duration. Although there is no significant difference between proton pump inhibitors with respect to healing of esophagitis, symptom relief occurs earlier with lansoprazole than omeprazole, and this is probably due to the greater oral bioavailability and faster onset of action of lansoprazole when compared to omeprazole.     

Does Helicobacter pylori infection contribute to gastroesophageal reflux disease?

Helicobacter pylori organisms that infect the stomach conceivably could contribute to esophageal inflammation in patients with gastroesophageal reflux disease (GERD) through any of at least three potential mechanisms: 1) by causing an increase in gastric acid secretion; 2) by spreading to infect the gastric-type columnar epithelium that occasionally can line the distal esophagus; and/or 3) by secreting noxious bacterial products into the gastric juice. Studies regarding these potential mechanisms are discussed in this report. Most investigations have found no apparent association between H. pylori infection and reflux esophagitis. Presently, infection with H. pylori does not appear to play an important role in the pathogenesis of GERD.     

Acid Reflux Directly Causes Sleep Disturbances in Rat with Chronic Esophagitis

Background & Aims

Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitor (PPI) therapy improves subjective but not objective sleep parameters in patients with GERD. This study aimed to investigate the association between GERD and sleep, and the effect of PPI on sleep by using a rat model of chronic acid reflux esophagitis.

Methods

Acid reflux esophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and then wrapping the duodenum near the pylorus. Rats underwent surgery for implantation of electrodes for electroencephalogram and electromyogram recordings, and they were transferred to a soundproof recording chamber. Polygraphic recordings were scored by using 10-s epochs for wake, rapid eye movement sleep, and non-rapid eye movement (NREM) sleep. To examine the role of acid reflux, rats were subcutaneously administered a PPI, omeprazole, at a dose of 20 mg/kg once daily.

Results

Rats with reflux esophagitis presented with several erosions, ulcers, and mucosal thickening with basal hyperplasia and marked inflammatory infiltration. The reflux esophagitis group showed a 34.0% increase in wake (232.2±11.4 min and 173.3±7.4 min in the reflux esophagitis and control groups, respectively; p<0.01) accompanied by a reduction in NREM sleep during light period, an increase in sleep fragmentation, and more frequent stage transitions. The use of omeprazole significantly improved sleep disturbances caused by reflux esophagitis, and this effect was not observed when the PPI was withdrawn.

Conclusions

Acid reflux directly causes sleep disturbances in rats with chronic esophagitis.     

4-aminobutyrate aminotransferase (ABAT): genetic and pharmacological evidence for an involvement in gastro esophageal reflux disease

Gastro-esophageal reflux disease (GERD) is partly caused by genetic factors. The underlying susceptibility genes are currently unknown, with the exception of COL3A1. We used three independent GERD patient cohorts to identify GERD susceptibility genes. Thirty-six families, demonstrating dominant transmission of GERD were subjected to whole genome microsatellite genotyping and linkage analysis. Five linked regions were identified. Two families shared a linked region (LOD 3.9 and 2.0) on chromosome 16. We used two additional independent GERD patient cohorts, one consisting of 219 trios (affected child with parents) and the other an adult GERD case control cohort consisting of 256 cases and 485 controls, to validate individual genes in the linked region through association analysis. Sixty six single nucleotide polymorphism (SNP) markers distributed over the nine genes present in the linked region were genotyped in the independent GERD trio cohort. Transmission disequilibrium test analysis followed by multiple testing adjustments revealed a significant genetic association for one SNP located in an intron of the gene 4-aminobutyrate aminotransferase (ABAT) (P_adj = 0.027). This association did not replicate in the adult case-control cohort, possibly due to the differences in ethnicity between the cohorts. Finally, using the selective ABAT inhibitor vigabatrin (γ-vinyl GABA) in a dog study, we were able to show a reduction of transient lower esophageal sphincter relaxations (TLESRs) by 57.3±11.4 % (p = 0.007) and the reflux events from 3.1±0.4 to 0.8±0.4 (p = 0.007). Our results demonstrate the direct involvement of ABAT in pathways affecting lower esophageal sphincter (LES) control and identifies ABAT as a genetic risk factor for GERD.     

Active and inactive gastroesophageal reflux diseases related to Helicobacter pylori therapy

We systematically reviewed the literature on gastroesophageal reflux disease (GERD) related to Helicobacter pylori therapy, and classified the GERD according to various aspects. Preexisting GERD is active GERD before H. pylori therapy, and a substantial proportion of the GERD patients improve after successful H. pylori therapy. If the GERD does not persist or recur after cessation of acid-suppressive therapy combined with H. pylori therapy, it may have been cured (cured GERD). If it recurs, it may have been masked by acid-suppressive therapy and unmasked with cessation of the therapy (pharmacologically masked and unmasked GERD). Newly developed GERD after successful H. pylori therapy is a kind of unmasked GERD arising after cure of infection (de novo unmasked GERD). The possible mechanism of the improvement of cured GERD is normalized hyperacidity associated with an improved cytokine-somatostatin-gastrin system followed by normalized G-cell activity and parietal cell mass. Preexisting GERD is not a reason to avoid eradication therapy. De novo unmasked GERD develops in a substantial proportion of patients with cured infection. The possible mechanism is increased acid exposure in the esophagus due to gastric acid increase, which is caused by a loss of neutralizing effect by ammonia, normalized cytokine-acid suppression and improvement of corpus atrophy. De novo unmasked GERD is important because GERD is recurrent and may induce adenocarcinoma of the esophagus. However, it is expected that cure of infection lowers gastric cancer incidence. Eradication therapy is recommended irrespective of the possibility that de novo unmasked GERD may have a slight increase of the risk of esophageal adenocarcinoma.     

Differences in activity and phosphorylation of MAPK enzymes in esophageal squamous cells of GERD patients with and without Barrett's esophagus

We hypothesized that, in esophageal squamous epithelial cells, there are differences among individuals in the signal transduction pathways activated by acid reflux that might underlie the development of Barrett's esophagus. To explore that hypothesis, we immortalized nonneoplastic, esophageal squamous cells from patients with gastroesophageal reflux disease (GERD) with (NES-B3T) and without (NES-G2T) Barrett's esophagus and used those cells to study acid effects on MAPK proteins. During endoscopy in patients with GERD with and without Barrett's esophagus, we took biopsy specimens from the distal squamous esophagus to study MAPK proteins before and after esophageal perfusion with 0.1 N HCl. We used immunoblotting and Western blotting to study MEK1/2 phosphorylation at two activating sites (serines 217/221), MEK1 phosphorylation at an inhibitory site (threonine 286), and MEK1/2 activity. After acid exposure, both cell lines exhibited increased MEK1/2 phosphorylation at the activating sites; the NES-B3T cells had higher levels of MEK1 phosphorylation at the inhibitory site, however, and only the NES-G2T cells showed an acid-induced increase in MEK1/2 activity. Similarly, in the squamous epithelium of patients with GERD with and without Barrett's esophagus, acid perfusion increased MEK1/2 phosphorylation at the activating sites in both patient groups; the Barrett's patients had higher levels of MEK1 phosphorylation at the inhibitory site, however, and only the patients without Barrett's demonstrated an acid-induced increase in ERK1/2 phosphorylation. In esophageal squamous cell lines and biopsies from patients with GERD with and without Barrett's esophagus, we have found differences in MAPK pathways activated by acid exposure. We speculate that these differences might underlie the development of Barrett's metaplasia.     

Multichannel intraluminal impedance accurately detects fasting,recumbent reflux events and their clearing

Multichannel intraluminal impedance (MII) is a new diagnostic test for gastroesophageal reflux disease (GERD). The objective of this report is to determine the accuracy of MII in detecting individual reflux events (REs) identified by pH probe and manometry, as well as their clearing in patients with severe GERD compared with normal volunteers. Ten severe GERD patients and 10 normal volunteers underwent simultaneous manometry [7 sites: gastric, lower esophageal sphincter, esophagus (4), pharynx], pH, and MII (6 sites in esophagus) for 15 min in the left and right recumbent posture while fasting. We found that patients had 30-fold more REs than normal volunteers (41 +/- 11 vs. 1.3 +/- 0.4), and 95% of all REs were detected by MII. An average 15-fold fall in impedance with liquid and fivefold rise with gas made REs and their composition easy to detect with MII. In the right recumbent posture, nearly all REs detected by MII were liquid (98%, 98/100). In contrast, all 283 REs detected by MII in the left recumbent posture were gas. Nearly all REs detected by MII were cleared (98%, 368/374). Mean acid clearing time was threefold longer (47 s) than clearing time by either manometry (15 s) or MII (13 s), primarily due to acid rereflux, i.e., additional acid REs during acid clearing. We conclude that MII is accurate in detecting REs identified by manometry and/or pH probe, their composition, and their clearing.     

In GERD patients, mucosal repair associated genes are upregulated in non-inflamed oesophageal epithelium

Previous studies addressing the effects of acid reflux and PPI therapy on gene expression in oesophageal epithelium concentrated on inflamed tissue. We aimed to determine changes in gene expression in non-inflamed oesophageal epithelium of GERD patients. Therefore, we included 20 GERD patients with pathological total 24-hr acid exposure of 6–12% and SAP ≥ 95%. Ten patients discontinued PPI treatment (PPI-), 10 took pantoprazole 40 mg bid (PPI+). Ten age/sex-matched healthy controls were recruited. Biopsies were taken from non-inflamed mucosa 6 cm and 16 cm proximal to the squamocolumnar junction (SCJ). Gene expression profiling of biopsies from 6 cm was performed on Human Genome U133 Plus 2.0 arrays (Affymetrix). Genes exhibiting a fold change >1.4 (t-test P -value < 1^E– 4) were considered differentially expressed. Results were confirmed by real-time RT-PCR. In PPI- patients, 92 microarray probesets were deregulated. The majority of the corresponding genes were associated with cell–cell contacts, cytoskeletal reorganization and cellular motility, suggesting facilitation of a migratory phenotype. Genes encoding proteins with anti-apoptotic or anti-proliferative functions or stress-protective functions were also deregulated. No probesets were deregulated in PPI+ patients. QPCR analysis of 20 selected genes confirmed most of the deregulations in PPI- patients, and showed several deregulated genes in PPI+ patients as well. In the biopsies taken at 16 cm QPCR revealed no deregulations of the selected genes. We conclude that upon acid exposure, oesophageal epithelial cells activate a process globally known as epithelial restitution: up-regulation of anti-apoptotic, anti-oxidant and migration associated genes. Possibly this process helps maintaining barrier function.     

胃食管反流病患者餐后近端胃内酸分布及与食管酸暴露的关系

目的:探讨餐后胃食管反流病(GERD)病人近端胃内酸度的分布状态及其和食管酸暴露的相关性。方法:抽选我院12例GERD患者,应用3级锑电极对定位于LES上缘近侧5 cm(食管)和LES上缘远侧5 cm的贲门下(近端胃内)、LES上缘远侧10cm的近端胃远侧(近端胃内)进行pH监测,监测时间为空腹1 h和餐后4 h,同期抽选健康志愿者12例为对照组,计算两组患者食管酸暴露以及胃内整合酸度(IA)。结果:两组空腹时近端胃内IA和食管酸暴露比较无显著性差异(P0.05);对照组中,试检者餐后1、2、3、4 h贲门下IA均显著低于近端胃远侧部位(P0.05),但GERD组中IA部位差异不明显(P0.05);餐后2 h,两组近端胃内IA均有所回升,但是对照组未超过基线(P0.05),而GERD组明显高于基线水平(P0.05);两组食管酸暴露均主要在餐后2h发生,并且两组比较差异显著(P0.05);在餐后各时段,两组中食管酸暴露与IA均无显著相关性。结论:GERD餐后晚期近端胃酸分泌增高,扩大了酸性近端胃池,可部分解释GERD进食后食管过度酸暴露。