幽门螺杆菌感染与儿童胃炎关系探讨

为进一步研究幽门螺杆菌（Helicobacter pylori,H.pylori)感染与儿童胃炎的关系，对我科1998年至2000年间500例3岁－15岁儿童胃镜活检组织进行组织学和H.pylori观察，按Sydney胃炎标准对病变分级，分析和探讨H.pylori感染与儿童胃炎发展变化的关系。结果表明：40.4%的儿童胃炎与H.pylori感染有关；而且炎症的程度、淋巴滤泡的形成、嗜酸细胞增多及幽门腺萎缩明显高于无H.pylori感染的儿童胃炎。提示上海地区儿童胃炎有很高的H.pylori感染率，H.pylori感染与儿童胃炎关系密切，儿童H.pylori胃炎的胃粘膜病理变化比非H.pylori感染者严重。     

PCR技术在儿童幽门螺杆菌感染中的应用

目的 建立一套适合儿童幽门螺杆菌感染的PCR检查方法，了解儿童幽门螺杆菌感染的可能途径。方法 对37例4～14岁患儿采用聚合酶链反应检测胃粘膜、胃液和唾液中的幽门螺杆菌，并作胃粘膜快速尿素酶、病理W—S银染色及细菌培养。结果 37例患儿中尿毒酶、病理W—S银染色、细菌培养、胃粘膜PCR、胃液PCR和唾液PCR的检出率分别为35．14％、40．54％、35．14％、45．95％、35．14％和5．40％；敏感性为68．8％、81．2％、81.3％、93．8％、81.3％、12．5％；特异性为90．5％、90．5％、100％、90．5％、100％、100％；2项或2项以上检出率阳性判断为幽门螺杆菌感染，37例患儿中阳性16例。结论 胃粘膜、胃液PCR方法同其他幽门螺杆菌检测手段相比幽门螺杆菌阳性检出率相似，PCR方法具有操作简便，特异性、敏感性高的优点，是诊断儿童幽门螺杆菌感染、判断药物疗效的有效检查手段。唾液PCR阳性率低可能与口腔缺乏特定的幽门螺杆菌生长环境有关，但也提示口-口传播是幽门螺杆菌感染的可能途径。     

粪便标本抗原检测诊断儿童幽门螺杆菌感染

目的 进行非侵入性粪便标本幽门螺杆菌抗原检测诊断儿童幽门螺杆菌(H.pylori)感染,并评价此试验方法的应用价值。方法：选择有上消化道症状的48例患儿为研究对象,采用H.pylori抗原检测试剂盒,以酶联免疫分析双抗体夹心法检测粪便H.pylori抗原,并与胃粘膜活检标本快速尿素酶试验、组织学、血清学试验作对比研究。结果：4种诊断试验诊断准确率分别为：粪便抗原试验95.8%,快速尿素酶试验95.9%,组织学97.9%,血清学83.7%。粪便抗原试验的特异度和敏感度分别为100%,93.6%。结论：粪便标本H.pylori 抗原试验诊断儿童幽门螺杆菌感染有较高的准确率、敏感性和特异性,为新的简便易行的非侵入性方法。     

无锡地区散居儿童幽门螺杆菌感染及相关因素流行病学调查

目的了解无锡地区儿童人群中幽门螺杆菌(H．pylori)感染率，探讨影响H．pylori感染的因素。方法采用酶联免疫分析法检测1126例0—12岁健康儿童及其父母粪便中的幽门螺杆菌抗原(HpSA)。并对每位人选者进行问卷调查，对其平时有无消化道症状、生活环境、生活习惯及家族史等情况进行了解。结果本地区儿童平均H．pylori感染率为19．1％，其中男性为19．6％，女性为18．5％，两者差异无显著性。有症状组阳性率为26．％，无症状组为10．6％。城区儿童H．pylori感染率为12．5％，城郊结合部儿童为19．3％，郊区、农村儿童为24．9％。结论无锡地区儿童中H．pylori感染率较高．有随年龄递增的趋势。幽门螺杆菌感染为引起无锡地区儿童胃十二指肠疾病的主要原因。     

婴幼儿幽门螺杆菌感染的临床及病理研究

目的为探讨婴幼儿慢性胃炎的幽门螺杆菌(H.pylori)感染与不同类型胃炎之间的关系及组织病理学的特征。方法评估5年内采用胃镜和胃粘膜病理组织学检查特征,及H.pylori检测的结果。结果152例婴幼儿慢性胃炎中H.pylori感染率为15.8%。各种不同类型的慢性胃炎中,以胃镜下结节性胃炎和消化性溃疡伴慢性胃炎组的H.pylori感染率为高,分别为33.3%和28.6%。中-重度粘膜炎症的病例H.pylori阳性组明显高于阴性组(P<0.05);H.pylori的菌量与胃粘膜的病理变化、炎症程度密切相关;H.pylori阳性组的家庭成员中13C?UBT检测阳性率为54%。结论H.pylori感染起始于婴幼儿,并与胃十二指肠疾病有一定关系,与胃镜下结节性胃炎和消化性溃疡最为密切;胃粘膜病理炎症程度与H.pylori的菌量密切相关;家庭成员中H.pylori感染可能是婴幼儿感染的来源。     

幽门螺杆菌菌株类型与儿童胃粘膜炎症程度的关系探讨

目的探讨幽门螺杆菌菌株类型与儿童胃粘膜炎症程度之间的关系。方法采用免疫印迹法测定134例幽门螺杆菌感染患儿血清细胞毒素相关蛋白(CagA)、空泡毒素(VacA)抗体,对幽门螺杆菌进行分型,并观察胃粘膜病理变化。结果CagA、VacA抗体总检出率分别为85.07%(114/134例)、91.04%(122/134例),检出幽门螺杆菌I型菌株113例,Ⅱ型菌株11例,中间型菌株10例,各型菌株感染引起胃粘膜中重度炎症分别为100例(88.50%)、5例(45.45%)、5例(50.00%),I型菌株与II型菌株、中间型菌株比较,差异有显著性(Hc=20.05,P<0.01)。结论幽门螺杆菌菌株类型与儿童胃粘膜炎症程度有关,I型菌株能引起较重的胃粘膜炎症。     

儿童幽门螺杆菌根除后复燃与再感染

为探讨儿童在幽门螺杆菌（H.pylori)根除后的复发情况，对90例H.pylori相关性胃十二指肠疾病，在抗H.pylori根除治疗后确定为H.pylori根除的患儿跟踪随访。结果90例儿童中复发23例，总复发率为25．56％。根除后1年内复发率为26．32％（10／38例）；根除后1年以上复发率为25．00％（13／52例），其中1年－11／2年为11．11％（2／18例）、11／2年－2年为20．22％（3／15例）、2年以上为40．11％（8／9例），P＜0．05。不同治疗方案与疗程的病例在1年内的复发率差异无显著性。H.pylori根除后1年以上，复发率呈逐步上升趋势。     

昆明白族儿童幽门螺杆菌感染与HLA-DR/DQB1的免疫遗传学分析

目的了解昆明白族儿童幽门螺杆菌感染与HLA-DR/DQB1等位基因的相关性。方法采用聚合酶链反应-序列特异性引物技术对符合流行病学诊断标准的36例H.pylori感染患儿及34例非感染儿童进行HLA-DR/DQB1基因分型。结果感染组检出15种DRB1等位基因,非感染组检出11种DRB1等位基因,两组均检出7种DQB1等位基因;组间各等位基因频率经检验,差异无统计学意义。结论白族儿童中H.pylori感染和非感染组的HLA-DR/DQB1等位基因频率无免疫遗传学差异;白族儿童H.pylori感染与HLA-DR/DQB1可能无关。     

过敏性紫癜伴幽门螺杆菌感染患儿肠道菌群变化的研究

目的 研究过敏性紫癜(HSP)伴有幽门螺杆菌(H.pylori)感染患儿肠道菌群的变化.方法 随机收集40例HSP患儿及40例正常儿童的粪便标本,先用快速免疫检测卡进行粪便幽门螺杆菌抗原(HpSA)检测,判定有无H.pylori感染.然后提取两组粪便标本目标细菌DNA,采用16SrRNA荧光定量PCR技术对两组粪便标本中的双歧杆菌和大肠杆菌进行定量分析和比较.并计算双歧杆菌/大肠杆菌(B/E)比值.结果 HSP患儿H.priori检出率为50.0%,正常儿童为27.5%(x2=4.266.P<0.05).双歧杆菌在HSP伴H.Pylori感染组和HSP非H.pylori感染组分别与正常儿童H.pylori感染组和非H.pylori感染组相比,数鼍明显减少(P<0.008 3);大肠杆菌在正常儿童H.pylori感染组和非H.pylori感染组分别与HSP非H.pylori感染组相比,数量明显升高(P<0.008 3),在HSP伴H.pylorii感染组与HSP非H.pylori感染组相比,数量明显升高(P<0.008 3).B/E值在HSP伴H.pylori感染组分别与HSP非H.pylori感染组、正常儿童H.priori感染组和正常儿童非H.pylon感染组相比,数值明显降低(P<0.008 3).结论 HSP患儿H.pylori检出率较正常儿童明显增多,HSP发病可能与H.pylori感染有关.HSP伴H.pylori感染和HSP非H.pylori感染患儿肠道双歧杆菌均较正常儿童减少,HSP伴H.pylori感染患儿肠道大肠杆菌较HSP非H.pylori感染息儿升高,HSP伴H.pylori感染患儿B/E值明显降低,提示HSP患儿肠道菌群失调明显.     

儿童幽门螺杆菌感染的诊断和治疗进展

已知幽门螺杆菌（H．pylori）是全球最常见的感染源之一，全球约50％人感染幽门螺杆菌，发展中国家的感染明显高于发达国家。消化系统许多疾病如慢性胃炎、消化性溃疡、MALT淋巴瘤、胃癌等疾病的发生与幽门螺杆菌的感染密切相关。     

幽门螺杆菌菌株类型与儿童上消化道疾病的关系

目的：幽门螺杆菌（Helicobacter pylori,Hp）感染已被确立为是引起慢性浅表性胃炎和消化性溃疡的重要病因，是胃癌和胃黏膜相关性淋巴样组织（MALT）淋巴瘤的重要危险因素。Hp的致病性与毒力有关，而细胞毒素相关蛋白（CagA）和空泡毒素（VcaA）是Hp的主要毒力因子之一。该研究通过了解Hp菌株类型与儿童胃十二指肠疾病类型及胃窦黏膜病理组织学变化的关系，探讨Hp感染的分型诊断是否有助于判断儿童胃十二指肠疾病的严重程度。方法：采用免疫印迹法对115例有上消化道症状的患儿进行Hp的血清学分型，并行胃镜检查，观察胃十二指肠疾病类型。取胃窦黏膜经Harris配方苏木精染色观察胃窦黏膜病理组织学变化、亚甲基蓝染色观察Hp感染情况。结果：115例患儿中检出Hp Ⅰ型菌株84例（73.0%），中间型菌株21例（18.3%），Ⅱ型菌株10例（8.7%）；Ⅰ型菌株引起胃窦黏膜中、重度炎症分别为83例、1例；中间型菌株引起胃窦黏膜中度炎症21例；Ⅱ型菌株引起胃窦黏膜轻度炎症2例，中度炎症8例，经统计学处理，各型菌株在引起胃窦黏膜炎症程度上差异有显著性（χ2=15.444，P<0.01），Ⅰ型菌株感染引起胃窦黏膜炎症程度最重，Ⅱ型菌株感染引起胃窦黏膜炎症程度最轻；而在活动性、萎缩的发生率上，各型差异无显著性（P＞0.05）；在淋巴滤泡形成的发生率上，各型差异有显著性（χ2=10.171，P<0.01）。各型菌株引起胃镜下胃、十二指肠疾病类型的构成比无明显差异（P＞0.05）。结论：该地区儿童Hp感染以Ⅰ型菌株最为多见。各型菌株100%存在胃窦黏膜组织学改变。Ⅰ型菌株感染所致胃窦黏膜炎症程度最重，且引起淋巴滤泡形成的发生率最高。Hp感染的分型诊断无助于对儿童胃、十二指肠疾病类型的判断，但有助于对儿童胃、十二指肠疾病病情的判断，Ⅰ型菌株感染者需要更为积极的治疗，对于Hp感染的儿童无论其血清分型如何，均应引起重视，并长期随访。［中国当代儿科杂志，2007，9（3）：201-204］     

幽门螺杆菌感染儿童胃黏膜细胞凋亡相关蛋白的研究

目的：旨在研究儿童胃黏膜细胞凋亡相关蛋白p53和Bax的表达水平与幽门螺杆菌（Hp）感染的关系。方法：采用免疫组化法检测了33例胃黏膜病变儿童胃黏膜上皮细胞中p53和Bax表达水平,并采用快速尿素酶试验和组织病理学检测两种方法检查这些病例的Hp感染情况。结果：在17例Hp阳性组织标本中,15例（88%）p53表达阳性,而在16例Hp阴性组织标本中,9例（56%）呈阳性。分析Bax的表达水平发现,在17例Hp阳性组织标本中,13例（76%）标本Bax表达呈阳性,而在16例Hp阴性组织标本中,6例 （38%）呈阳性。统计学分析显示,Hp阳性标本的p53和Bax表达水平要明显高于Hp阴性标本（P<0.05）。结论：儿童期Hp感染与胃黏膜上皮细胞p53蛋白和Bax蛋白过度表达密切相关。［中国当代儿科杂志,2010,12（2）：110-112］     

上海地区部分儿童幽门螺杆菌cagA、vacA、iceA基因型别分析

目的：了解上海部分地区儿童感染幽门螺杆菌（Hp）的cagA、vacA、iceA的基因亚型,探讨其与儿童上消化道疾病的关系。方法：收集2007年5月至2008年1月在我院行胃镜检查确诊Hp感染59例患者的胃黏膜组织,分别进行聚合酶链反应（PCR）检测cagA、vacA和iceA基因;病理检查胃窦黏膜炎症程度;酶联免疫吸附试验（ELISA）检测胃窦黏膜IFN-γ 和IL-4的含量。结果：cagA基因单独检出率为65%（37/57）,vacAs1/m1单独检出率为19%（11/57）,vacAs1/m2单独检出率为40%（23/57）,iceA1单独检出率为63%（36/57）,iceA2单独检出率为19%（11/57）,9%（5/57）的菌株iceA1 和iceA2均阳性。不同基因型菌株在慢性胃炎和消化性溃疡中的检出率差异无统计学意义（P>0.05）。不同基因型菌株与胃窦黏膜炎症的严重程度无关（P>0.05）。不同基因型菌株感染的胃窦黏膜IFN-γ、IL-4的含量差异亦无统计学意义（P>0.05）。结论：cagA/vacAs1/m2/iceA1为上海部分地区儿童中Hp的优势基因型。除了菌株因素外,宿主基因多态性、环境因素对于疾病的发生、发展也发挥了重要作用。［中国当代儿科杂志,2010,12（4）：267-271］     

Cytokines in the gastric mucosa of children with Helicobacter pylori infection

AIM: Few studies have looked at the cytokine profile in gastric mucosa in children with Helicobacter pylori infection. This study investigated cytokines and their effects on histological abnormalities in the gastric mucosa of children with H. pylori infection. METHODS: The levels of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and IL-8 proteins were measured in biopsy specimens from the gastric antrum and corpus of children with H. pylori infection, and related to inflammatory cell infiltrations. RESULTS: The antral and corporal mucosal levels of IFN-gamma and IL-8 proteins were significantly higher in children with H. pylori infection than in uninfected children, but there was no such difference in the levels of IL-4 protein. The antral mucosal level of IL-8 protein was significantly higher than the corporal mucosal level of IL-8 protein in the infected children. Inflammatory cell infiltration was significantly higher in the infected children than in the uninfected children, but there were no significant correlations between mucosal cytokine levels and inflammatory cell infiltrations. CONCLUSION: The results suggest that the predominant Th1 cytokine response and enhanced IL-8 production in the mucosa may be involved in the gastric inflammation seen in children infected with H. pylori, as well as in adult patients.     

Helicobacter pylori and Meckel's diverticula

BACKGROUND: Helicobacter pylori is known to infect only gastric mucosa and is strongly associated with gastroduodenal ulceration. The authors studied whether H. pylori colonizes the gastric mucosa of Meckel's diverticula, and determined its relationship to "gastritis" and bleeding. METHODS: A 10-year retrospective review identified 45 children with Meckel's diverticulum. Hematoxylin-eosin and Diff-Quik stains were used to assess the presence and severity of gastritis, and to highlight organisms in the resected diverticula. Cases with organisms were then studied with antibodies specific for H. pylori using immunoperoxidase methods. RESULTS: Twenty-eight children, 7 months to 12.6 years of age, had lower gastrointestinal hemorrhage caused by Meckel's diverticulum and had positive radionuclide scans. All had acid-secreting mucosa in their diverticula, and ulceration. "Chronic gastritis" and eosinophilia were constant findings; "acute gastritis" was present in four patients. Twenty specimens exhibited lymphoid follicles in the gastric mucosa. Seventeen patients with Meckel's diverticula (age range, 1 month-14.7 years) who presented with acute abdominal pain associated with intussusception were used for comparison. Acid-secreting gastric mucosa was seen in four patients. H. pylori was identified in only one of the 45 patients; this patient had ulceration and moderate "acute gastritis." CONCLUSIONS: H. pylori does not colonize a substantial number of children who have ulcerated and bleeding Meckel's diverticulum in the presence of acid-secreting mucosa. Although H. pylori is a notable cause of ulceration, the authors confirm that ulceration is possible in its absence, and alternative mechanisms of ulceration are important. The presence of lymphoid follicles in Meckel's diverticula, unlike gastric biopsies, is not associated with H. pylori.     

Testing for serum IgG antibodies to Helicobacter pylori cytotoxin-associated protein detects children with higher grades of gastric inflammation.

BACKGROUND: Little information is available about the relationships between Helicobacter pylori cytotoxin-associated protein (CagA) and clinicopathologic features in children. The purpose of this study was to test whether determining serum IgG antibodies to CagA is a useful tool for detecting more severe disease. METHODS: One hundred twenty-seven consecutive children (age range, 0.75-17.8 years; median, 9.4 years) referred for gastroscopy were included in the study. Antral and corpus biopsies were taken for gastric histology and H. pylori detection. Major symptoms and endoscopic findings were recorded. A serum sample was drawn from each child and assayed for IgG antibodies CagA by a commercial enzyme-linked immunosorbent assay. RESULTS: Sixty-three (50%) children had no evidence of H. pylori infection, 28 (22%) were H. pylori positive/CagA positive, and 36 (28%) were H. pylori positive/CagA negative. There were no differences in clinical diagnosis and occurrence of any predominant symptom according to H. pylori and CagA status. Findings of antral nodularity were more frequent (p = 0.003) in H. pylori-positive/CagA-positive children than in H. pylori-positive/CagA-negative children. The gastritis score was significantly higher in H. pylori-positive/CagA-positive children than in H. pylori-positive/CagA-negative children (5.7 +/- 1.9 vs. 3.8 +/- 1.6, respectively; p = 0.0003), either in the antral (p = 0.0002) or in the corpus (p = 0.001) mucosa. Inflammation (p = 0.0001) and activity (p = 0.0001) scores were both higher in H. pylori-positive/CagA-positive children than in H. pylori-positive/CagA-negative children, but the H. pylori density score was not significantly different (p = NS). In no case was normal gastric mucosa found in H. pylori-positive/ CagA-positive children. Lymphocytic gastritis (p = 0.0008) and lymphoid follicles (p = 0.000003) were a more frequent finding in H. pylori-positive children than in H. pylori negative children, irrespective of CagA status. CONCLUSION: Testing for serum IgG to CagA detects higher grades of gastric inflammation among children with H. pylori infection. It may be useful in targeting H. pylori-positive/ CagA-positive children for antimicrobial therapy while reducing the need for endoscopy and gastric biopsy.     

Upper gastrointestinal disease, Helicobacter pylori and recurrent abdominal pain

Over a 5-y period, 396 children complaining of recurrent abdominal pain (RAP) underwent upper gastrointestinal endoscopy in order to identify any underlying organic pathology and determine the prevalence of Helicobacter pylori (H. pylori) infection. Histologically confirmed mucosal inflammation was found in 338 out of 396 children (85.4%); in 113 of 396 patients (28.5%), H. pylori was identified on the gastric mucosa. Significant discriminating factors between H. pylori positive and negative children with RAP included age (mean age for positive 11 y vs. 8.1 y for negative, p < 0.01) and gender (male gender predominance in the H. pylori positive, p < 0.001). No significant difference was found between H. pylori positive and negative groups regarding incidence and character of the presenting symptoms. All H. pylori positive children (100%) had abnormal histology compared with 225 out of 283 negative ones (79.5%). Histologically confirmed gastritis was the most prominent finding in H. pylori positive children compared with H. pylori negative (98.2% vs. 19%, p < 0.001). Conversely, oesophagitis was more common in H. pylori negative children (47.7% vs. 27.4%, p < 0.001). The incidence of peptic ulcer was higher in H. pylori infected patients than in the H. pylori negative group (5.3% vs. 1%, p < 0.05). Our data suggest that gastrointestinal pathology is more common than previously thought in children with RAP, while H. pylori infection is a relatively important factor in the etiology of upper gastrointestinal inflammation in RAP syndrome.     

Gastric emptying of solids in children with H. pylori-positive and H. pylori-negative non-ulcer dyspepsia

OBJECTIVE: There is currently no data available in children on possible relationships among Helicobacter pylori, gastric motility and gastric inflammation. This is a prospective study of gastric emptying (GE) in symptomatic children with and without H. pylori who met symptom-based criteria for non-ulcer dyspepsia (NUD). METHODS: 47 consecutive dyspeptic patients (23 males; age range, 7 to 18 years) were enrolled. All patients had extensive negative diagnostic investigations. Scintigraphic solid-phase gastric emptying was assessed. RESULTS: 21 H. pylori-positive and 26 H. pylori-negative patients were identified with non-ulcer dyspepsia. The groups were not different in clinical symptoms except that pain related to feeding was more frequent in infected children (P < 0.03). Nodular antral gastritis was found more frequently in the H. pylori positive group (P < 0.0001). The gastritis score was more severe in H. pylori infected than H. pylori negative patients in both fundic and body mucosa (P < 0.001). Within the H. pylori-positive NUD group, the mean half-time GE of a solid meal was significantly accelerated compared to the non-infected group (P < 0.05). There was no difference in the intragastric food distribution and curves of gastric emptying of both groups. A significant relationship was found between the degree of gastric body inflammation gastric emptying, but not antral inflammation. Gastric emptying rate did not differ by sex or age of the subjects in either group. CONCLUSIONS: In dyspeptic children with H. pylori, gastric emptying of a solid was significantly accelerated compared with symptomatic H. pylori uninfected patients. This suggests that H. pylori is able to induce gastric emptying acceleration. Our findings add more information on H. pylori infection and gastroduodenal disease.     

Effect of Helicobacter pylori eradication on the natural history of duodenal ulcer disease.

BACKGROUND: Duodenal ulcer disease is strongly associated with Helicobacter pylori infection of the gastric mucosa. Eradication of H pylori from the gastric mucosa in adults is associated with long term healing of ulcers. AIMS: To follow a cohort of children with duodenal ulcer disease for a minimum of two years after the eradication of H pylori. PATIENTS AND METHODS: Over a three year period, all children diagnosed with duodenal ulcer disease had their symptoms documented and their H pylori status evaluated. The histories of these children were carefully screened to determine previous symptoms and to document previous treatment regimens. RESULTS: Sixteen children were diagnosed with ulcers and 15 were available for treatment and long term follow up. The median age at which symptoms first occurred was 10.5 years (range, 6-14) and the median duration of symptoms was 24 months (range, 2-60). Ten of the children had been treated with H2 receptor antagonists for a median of 3.5 months (range, 1-60). Duodenal ulcers healed in all children after eradication of H pylori and all children have remained asymptomatic for a median of 37 months (range, 26-62). No child has required subsequent admission to hospital. CONCLUSION: Eradication of H pylori is very effective in the long term healing of duodenal ulcer disease. H pylori eradication should be the standard treatment for all infected children who present with duodenal ulcer disease.