Experimental reflux esophagitis in rats. A scanning electron-microscopic investigation

We investigated the morphological alterations of the esophageal mucosa due to reflux disease by scanning electron microscopy. The esophagi of several rats were perfused with hydrochloric acid in the lower third, which was sealed towards the cardia with an inflatable catheter. Our findings indicate extensive erosion of the esophageal mucosa with detachment of the epithelial layer and underlying lamina propria from the lamina muscularis mucosae. The esophagi of control animals were perfused with physiologic saline solution and displayed no evidence of erosion or ulcerous alterations.     

Management of vesicoureteral reflux

Four cases of vesicoureteral reflux are discussed by prominent pediatric urologists. The condition can range from minimal reflux into the distal ureter to massive reflux causing tortuosity of the ureter and hydronephrosis. Treatment options range from medical management to tapering of the ureter with reimplantation. The cross-trigonal technique is popular among pediatric urologists, and the Politano-Leadbetter technique is a very successful technique that has stood the test of time. The extravesical approach to ureteral reimplantation reduces morbidity, shortens hospital stays, reduces medical costs, and maintains the high success rates of the intravesical techniques. Subureteric injection of bulking agents to correct the reflux holds promise as an alternative to open surgery, but presents the challenge of identifying the ideal bulking agent.     

探讨不同浓度的清郁和降汤对反流性食管炎大鼠肠道菌群的影响

【目的】观察不同浓度的清郁和降汤对反流性食管炎（reflux esophagitis,RE）的治疗效果,并探讨其对肠道菌群的影响。【方法】将36只健康雄性SD大鼠随机分为6组,其中1组为假手术组,剩余5组大鼠采用“前胃结扎+外置幽门部分结扎术”手术造模方法建立反流性食管炎模型。造模2周后将术后全部存活的30只大鼠随机分成对照组、中药高剂量组（予高剂量清郁和降汤）、中药中剂量组（予中剂量清郁和降汤）、中药低剂量组（予低剂量清郁和降汤）、西药组（予泮托拉唑钠肠溶胶囊+枸橼酸莫沙比利分散片+复方嗜酸乳杆菌片）,每组6只。于术后第15天开始灌胃,其中假手术组及对照组予蒸馏水灌胃,其他组分别给予相应的药物灌胃,持续灌胃14 d后将所有大鼠处死后进行取材。以苏木精-伊红（hematoxylin-eosin,HE）染色观察大鼠食管组织的病理学改变;采用16S rRNA基因高通量测序检测其肠道黏膜的菌群构成。【结果】反流性食管炎大鼠存在着较为明显的肠道菌群结构变化及肠道菌群多样性较低的情况,B组（对照组）中厚壁菌门和拟杆菌门占比减少,变形菌门占比增多,且假单胞菌属、青枯菌属等细菌增多。低、中、高3种浓度的清郁和降汤均能够提升RE大鼠的肠道菌群多样性,增加拟杆菌门及厚壁菌门,降低变形菌门的占比,从属水平上看,清郁和降汤能够提升大鼠肠道中拟杆菌属、乳杆菌属、瘤胃球菌属、颤螺旋菌属、双歧杆菌属和狄氏副拟杆菌属等益生菌占比。以D组（中剂量组）对大鼠肠道菌群多样性提升最为明显,其效果最接近假手术组。特征微生物方面,B组以变形菌门为特征性微生物,D、E两组出现了放线菌门及拟杆菌门下属细菌为特征微生物的情况,在门水平与F组相同。【结论】清郁和降汤能够有效地治疗反流性食管炎,其机制可能与改变RE大鼠的肠道菌群结构、减少有害菌、提升益生菌的占比和改善肠道菌群多样性有关。     

Specific induction of a 72-kDa heat shock protein protects esophageal mucosa from reflux esophagitis

AimsThe aim of this study is to investigate the expression and cytoprotective function of a 72-kDa heat shock protein (HSP72) using a reflux esophagitis model in rats.Main methodsExpression of HSP60, HSP72, and HSP90 in rat esophageal mucosa was evaluated by Western blot analysis before and after hyperthermia (42.5 °C, 20 min). Rats received the operation to produce reflux esophagitis with or without pretreatment with hyperthermia to induce HSPs. The esophageal mucosal damage was evaluated 12 h after the operation.Key findingsExpression of HSP72 was significantly increased by hyperthermia in rat esophageal mucosa. Reflux esophagitis was dramatically prevented when HSP72 was preinduced by hyperthermia. Furthermore, activation of TNF-α and IL-1β in esophageal mucosa was also suppressed.SignificanceThese results suggested that hyperthermia protects the esophageal mucosa in reflux esophagitis model by inducing HSP72 and suppressing proinflammatory cytokine activation. These findings might suggest that HSP-inducing therapy could be a novel and unique therapy for reflux esophagitis.     

Abnormal gastroesophageal flap valve is highly associated with endoscopic reflux esophagitis after Helicobacter pylori eradication

BACKGROUND: Whether or not eradicating Helicobacter pylori worsens reflux esophagitis remains controversial. We investigated the relationship between gastroesophageal flap valve grading and endoscopic reflux esophagitis (in patients with peptic ulcer and gastritis) before and after H. pylori eradication in a case controlled study. Whether endoscopic assessment of the gastroesophageal flap valve allows prediction of endoscopic reflux esophagitis development or exacerbation was also assessed. MATERIALS AND METHODS: A total of 220 patients with peptic ulcer or chronic gastritis, who received H. pylori eradication therapy, were followed for at least 6 months (range, 6-34 months) for endoscopic changes. Another 88 age- and disease-matched H. pylori-positive controls, without eradication therapy, were also enrolled. Gastroesophageal flap valve grade (I-IV) was assessed using the Hill classification. RESULTS: Endoscopic reflux esophagitis incidence was significantly (p < .01) higher in abnormal gastroesophageal flap valve (grades III and IV) than in normal gastroesophageal flap valve (grades I and II) cases in both H. pylori eradication and control groups. The rate of new endoscopic reflux esophagitis after eradication was significantly (p < .01) higher in the abnormal than in the normal gastroesophageal flap valve group (54.5% vs. 9.1%). By contrast, the endoscopic reflux esophagitis exacerbation rate in patients with endoscopic reflux esophagitis before eradication was low (4.5%) and endoscopic reflux esophagitis improvement was observed in 40.9% of these patients. CONCLUSIONS: These results suggest gastroesophageal flap valve grading by endoscopy to be useful for predicting the risk of newly developing endoscopic reflux esophagitis after H. pylori eradication, in addition to predicting the presence of endoscopic reflux esophagitis.     

Negative association between Helicobacter pylori infection and reflux esophagitis in older patients: case-control study in Japan

Background. Recent studies have clarified a close association between H. pylori infection and gastritis, peptic ulcer disease, and gastric cancer, but there is little information concerning the relationship between H. pylori infection and reflux esophagitis (RE). We investigated the relationship between H. pylori , RE, and corpus gastritis.
Subjects and Methods. Ninety-five patients with RE and 190 sex- and age-matched asymptomatic healthy controls demonstrating no localized lesions in the upper GI tract were studied and evaluated for H. pylori infection, histologic gastritis, serum gastrin, and pepsinogens (PGs).
Results. H. pylori infection was significantly lower in RE patients than in asymptomatic controls (41% vs. 76%, p < .01). Histologic gastritis of both the antrum and corpus was significantly less frequent (antrum; p < .01, corpus; p < .01), and serum levels of PGI and the PG I/II ratio were significantly higher in RE patients than in controls (PGI; p < .05, PG I/II ratio; p < .01). When the subjects were divided into two age groups (59 years of age and younger and 60 years of age and older), a significant difference was found only among patients over 60 years of age (29% vs. 85%, p < .01). Among subjects in this age group, gastritis in both the antrum and corpus were significantly milder in RE patients than in controls. Although the prevalence of H. pylori infection was similar between the two groups of patients under 59 years of age, corpus gastritis was significantly milder in patients than in controls ( p < .05).
Conclusions. A significantly low prevalence of H. pylori infection was found in RE patients over 60 years of age but not in those under 59 in comparison with sex- and age-matched controls. The relative lack of corpus gastritis might play a role in the pathogenesis of RE in our population through preservation of the acid secretion area.     

反流性食管炎患者口腔菌群变化及其与幽门螺杆菌感染的关系

探讨反流性食管炎（RE）患者口腔菌群变化及其与幽门螺杆菌（H. pylori）感染的关系,为该类患者的治疗提供参考。

选择南京同仁医院2019年5月至2021年5月收治的140例RE患者为研究对象,将A、B级RE患者纳入AB组,C、D级纳入CD组;同时将患者分为合并H. pylori感染组和未合并H. pylori感染组。以一次性无菌收集管收集患者唾液标本,使用Illumina Hiseq 2500高通量测序平台对合格文库进行双端测序。

AB组患者H. pylori阳性率（16.67%）低于CD组（45.45%）。AB组患者口腔菌群Chao 1指数和Shannon指数均高于CD组,Simpson指数低于CD组（均P＜0.05）。未合并H. pylori感染组患者口腔菌群Chao 1指数和Simpson指数高于合并H. pylori感染组,Shannon指数低于合并H. pylori感染组（均P＜0.05）。未合并H. pylori感染组患者口腔放线菌门、放线菌属相对丰度高于合并H. pylori感染组,拟杆菌门相对丰度低于合并H. pylori感染组（均P＜0.05）。

RE病情较重者和合并H. pylori感染者表现为口腔菌群α多样性降低和门、属水平菌群相对丰度改变,合并H. pylori感染对RE患者病情和口腔菌群会产生一定影响。

     

Chronic cough and gastroesophageal reflux.

We reviewed the charts of 20 patients with chronic cough of unknown cause who had been referred to a tertiary care respiratory centre from 1980 to 1984 to determine whether gastroesophageal reflux (GER) was a contributing factor. Fifteen of the patients complained of symptoms suggestive of GER: radiologic investigation of the upper gastrointestinal tract revealed hiatus hernia and GER in four, hiatus hernia alone in three, GER alone in two, decreased esophageal peristalsis in one and normal findings in four. Fibreoptic bronchoscopy in the four former smokers and one nonsmoker showed diffuse mucosal erythema. A chest x-ray film in one patient showed an infiltrate at the base of the right lung; transbronchial biopsy revealed vegetable material, which confirmed pulmonary aspiration. A 3-month course of medical antireflux treatment (dietary and lifestyle changes, elevation of the head of the bed and administration of cimetidine, antacid and metoclopramide) relieved the chronic cough in 14 of the 20 patients. Of the remaining patients one was lost to follow-up and five had GER confirmed by means of esophagoscopy, esophageal motility testing and long-term intraesophageal pH monitoring; four of the five patients underwent fundoplication and were asymptomatic 3 months after surgery. Antireflux therapy should be considered in patients with chronic cough when other causes have been ruled out, even if there are no GER symptoms. If the treatment fails, full investigation for GER is recommended; if GER is confirmed, surgery should be considered.