Blood levels of leukotrienes (LTC4, D4, E4, B4) and synthesis of leukotriene B4 by peripheral leukocytes in children with acute A and B hepatitis

Leukotrienes (LTs) are cell-membrane derived lipid inflammatory mediators, synthesized and eliminated by the liver. LTs have effects on liver cells in some pathological conditions. In this study, we measured plasma endogenous and liberated leukotriene (LT) concentration in peripheral blood leukocytes stimulated in vitro by the calcium ionophore (CaA23187) and platelet-activating factor (PAF). Production of LTs was measured in type A (n=37) and type B (n=10) acute hepatitis patients and control subjects (n=10). LTs levels were measured by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA). The concentration of LTB4 measured in plasma and stimulated peripheral blood leukocyte supernatants of children with hepatitis A infection was found to be statistically elevated and in positive correlation with serum alanine aminotransferase (ALT) levels. In plasma samples of hepatitis B patients, LTC4 and LTE4 were measured in significantly elevated concentrations. These results suggest that LTB4 may be a critical mediator of hepatitis A virus-induced hepatocellular injury.     

Increased mucosal inflammatory cytokines in children with Helicobacter pylori-associated gastritis

The concentrations of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1-β in tissue homogenates of gastric mucosal biopsy specimens, and in gastric juice samples from Helicobacter pylori-positive and -negative children, were determined. The study population comprised 30 children with recurrent abdominal pain attending upper gastrointestinal endoscopy. Of these patients 18 were infected with H. pylori. Cytokine concentrations in gastric biopsy homogenate supernatants and in gastric juice were measured by enzyme-linked immunosorbent assay (ELISA). TNF-α levels in gastric juice and in gastric biopsy homogenate supernatants in patients with H. pylori-positive gastritis were found to be significantly higher than those in children without H. pylori infection. IL-6 levels were also higher in H. pylori -infected subjects, but the difference in IL-6 concentrations measured in gastric juice and biopsy homogenate supernatants did not reach statistical significance. IL-1-β concentrations in both specimens showed no significant difference between the two groups of children. It was suggested that increased levels of inflammatory cytokines, especially TNF-α and IL-6 generated locally within the gastric mucosa might be implicated in the pathogenesis of H. pylori-associated gastritis in childhood.     

Helicobacter pylori infection and recurrent abdominal pain in children

The association of Helicobacter pylori infection with recurrent abdominal pain (RAP) was studied in 65 children aged between 3 and 12 years. Cases with a specific cause for abdominal pain were excluded from the study. All the patients were subjected to upper gastrointestinal endoscopy and antral biopsy. The biopsy specimens were subjected to rapid urease test, histopathological examination, and culture to document the presence of H. pylori in the gastric mucosa. All the patients were put on H. pylori eradication drugs for 10 days. About 69 per cent of the children had histopathological evidence of antral inflammation. Helicobacter pylori detection rate was 77 per cent. About 83 per cent of patients had complete symptomatic relief when followed over a period of 6 months. The study concludes a possible association of H. pylori with recurrent abdominal pain in children and all these patients should be considered for H. pylori eradication.     

Helicobacter pylori duodenal colonization in children

To investigate the prevalence and the significance of Helicobacter pylori duodenal colonization, endoscopic duodenal biopsies were performed in 168 children with chronic abdominal pain, gastroesophageal reflux, gastrointestinal bleeding, and malabsorption syndrome. Helicobacter pylori infection was detected in 68 children (40.4%): in 31 of them H. pylori was present in the gastric antrum, and in 37 in the duodenum also. Duodenitis was observed in 25 children with duodenal H. pylori ; gastric metaplasia in 3. Scanning electron microscopy revealed the presence of the micro-organism in 3/13 cases; the bacteria were located in the intercellular spaces and alterations of the epithelial surface were found. In conclusion, H. pylori gastritis in children is often associated with duodenal colonization which can cause duodenitis, and also without gastric metaplasia, which indicates a possible role of the micro-organism in the pathogenesis of the lesions.     

The prevalence and related symptomatology of Helicobacter pylori in children with recurrent abdominal pain

The aim of the study was to assess and compare the IgG seroprevalence of H. pylori in children with recurrent abdominal pain with healthy children and to investigate the related symptoms. IgG antibodies against low-molecular weight H. pylori antigens were assessed in 438 children with recurrent abdominal pain and in 91 healthy controls. Sera with an ELISA unit-value above the cut-off level were confirmed by Western immunoblot. Only seropositive children with recurrent abdominal pain were examined by an oesophago-gastro-duodenoscopy. Symptomatology was recorded according to the localization of the abdominal pain, presence of pyrosis, nocturnal pain, relation of pain to meals and bowel irregularities. The seroprevalence was 21% (95% CI: 17-25%) in the children with recurrent abdominal pain and 10% (95% CI: 5–18%) in the healthy controls ( p = 0:30). In seropositive children with RAP H. pylori was found in 46/66 by culture and histology. The presence of H. pylori was significantly associated with active or inactive chronic gastritis. The presence of H. pylori was associated with both parents being born in a country with a high prevalence and a low social class. Helicobacter pylori-positive children had more often pain related to meals than the H. pylori- negative children. No differences among the two groups were seen according to the levels of haemoglobin, leucocytes, thrombocytes, weight and height. In conclusion, the seroprevalence of H. pylori is comparable in children with recurrent abdominal pain and healthy children. No specific symptomatology was seen in H. pylori- positive children with RAP.     

Helicobacter pylori - dependent intragastric urea biodegradation in children: Diagnostic and pathogenetic importance

Abstract The objective of the present work was to study the relationship between intragastric urea hydrolysis generated by Helicobacter pylori urease and acid-peptic disease in childhood. Intragastric urease activity was examined by urea and ammonia concentration measurement in gastric juice in 91 children with upper abdominal complaints. Helicobacter pylori infection was detected from 70 (76.9%) of 91 patients, including all of the 15 subjects with peptic ulcer disease. Helicobacter pylori -related gastritis in children was associated with a decrease of urea and an increase of ammonia in gastric juice ( P < 0.001) in comparison with H. pylori-negative children. The gastritis score was correlated with the concentrations of urea and ammonia in the gastric juice of patients infected with H. pylori. There was a significant correlation between the histologically detected dissemination of organisms and gastric ammonia levels. Similar results were obtained concerning correlation between gastric juice ammonia and anti- H. pylori specific immunoglobulin G versus highly purified antigen of H. pylori containing urease. Present findings prove that H. pylori plays an essential role in the pathogenesis of gastritis and that ammonia is one of the main pathogenic factors of acid-peptic disease.     

Management and response to treatment of Helicobacter pylori gastritis.

Gastritis associated with Helicobacter pylori was present in gastric biopsies from 24/95 (25%) children and adolescents undergoing endoscopy for recurrent abdominal pain and upper gastrointestinal symptoms. H pylori associated gastritis occurred mainly in older children (8-16 years) and was significantly associated with low socioeconomic class and a family history of peptic ulcer disease. Antral nodularity was a common endoscopic finding in H pylori positive children. Eighteen children, all over 5 years of age, were treated with tripotassium dicitratobismuthate (De-Nol) for two months and ampicillin for two weeks. In 12 children follow up gastric biopsies were obtained six weeks after completion of treatment. In 9/12 (75%) children H pylori was eradicated, and gastritis improved.     

Correlation between Helicobacter pylori infection and vitamin C levels in whole blood,plasma, and gastric juice,and the pH of gastric juice in Korean children

BACKGROUND: It is well known that chronic gastritis induced by Helicobacter pylori may be associated with hypochlorhydria and may also be accompanied by low levels of vitamin C in plasma and gastric juice in adults. This study investigates the relationship between H. pylori infection and vitamin C levels in the blood, plasma and gastric juice and the gastric juice pH of Korean children. METHODS: During a 5-year period, multiple gastric antral biopsies were taken from 452 children who underwent gastroduodenoscopy. The biopsy specimen was inoculated into phenol red buffered urea broth and incubated for 48 hours to detect color changes. The histopathologic findings were evaluated using the Sydney System. Concentrations of vitamin C in whole blood, plasma, and gastric juice aspirate were measured using the 2,4-dinitrophenylhydrazine method. RESULTS: Four hundred fifty-two patients (228 boys, 224 girls) aged 1 to 15 years were enrolled in this study. H. pylori was detected in 112 patients (24.8%) using histology, whereas it was found in 204 patients (45.1%) using the urease test. One hundred seven patients (23.7%) had active gastritis, and 421 patients (93.1%) had chronic gastritis. Vitamin C levels in whole blood, plasma, and gastric juice exhibited significant negative correlation with the age of patients, the histologic density of H. pylori, the degree of active and chronic gastritis, and the severity of H. pylori infection (based on urease positivity and histologic density of H. pylori). Gastric juice pH was correlated with the degree of chronic gastritis and was significantly higher in urease-positive patients. CONCLUSIONS: The data demonstrate that vitamin C levels in whole blood, plasma, and gastric juice and the gastric juice pH in Korean children are closely related to the severity of H. pylori infection and the histologic changes in the stomach. These data suggest that vitamin C may play a role in determining infection and progression, and vitamin C supplementation may be an important axis for the management of H. pylori infection in children.     

The role of Helicobacter pylori in abdominal pain in children]

Helicobacter pylori (H. pylori) colonizes the human stomach, especially during childhood. H. pylori gastritis, in the absence of duodenal ulcer, does not appear to be associated with specific symptoms. After eradication of H. pylori infection, abdominal pain is improved only in children with duodenal ulcer. Children with H. pylori gastritis cannot be distinguished from uninfected children on the basis of initial symptoms. However, although not demonstrated, a relationship between H. pylori and recurrent abdominal pain might exist since some studies showed that H. pylori-infected children present more frequent pain related to meals or ulcer-like symptoms. These discrepancies could be explained by the fact that H. pylori is probably not a frequent cause of recurrent abdominal pain. The use of refined clinical characteristics of abdominal pain could be of help identifying a subgroup of patients with abdominal pain in whom H. pylori infection needs to be sought and treated. Recent pediatric consensus conferences recommend testing for H. pylori infection by endoscopy only those patients presenting symptoms suggestive of an organic origin.     

Helicobacter pylori infection in recurrent abdominal pain

BACKGROUND: Helicobacter pylori is associated with chronic gastritis and peptic ulcer in adults and in children. The purpose of the present study was to analyze the association of recurrent abdominal pain and H. pylori infection in children and to evaluate the efficacy of antimicrobial treatment in patients with evidence of infection. METHODS: The clinical and histopathologic findings in children who underwent diagnostic upper endoscopy for recurrent abdominal pain were analyzed retrospectively. Patients with evidence of infection with H. pylori were treated with a combination of omeprazole, amoxicillin, and clarithromycin. Efficacy of treatment was assessed using the 13C-urea-breath test. RESULTS: H. pylori was found in histopathologic sections of 29 (40%) of 73 patients undergoing diagnostic endoscopy for recurrent abdominal pain. Five children (17%) were of Swiss ethnic origin, and 24 (83%) were non-Swiss. All the infected patients had chronic gastritis and 4 (14%) had ulcerations in the duodenum. Treatment with omeprazole, amoxicillin, and clarithromycin resulted in eradication of the infection in all and in resolution of the clinical symptoms in 15 (80%) of 19 patients who had a follow-up examination. CONCLUSIONS: The presented data suggest that gastritis induced by H. pylori may be associated with recurrent abdominal pain and that in Switzerland infections with H. pylori primarily involve persons who are non-Swiss. A combined therapy results in eradication of the bacterium and in improvement of the clinical symptoms in a significant majority of the patients.     

胃液实时聚合酶链反应检测儿童幽门螺杆菌及宿主基因型的临床研究

目的探讨胃液实时聚合酶链反应(real-time PCR)检测儿童幽门螺杆菌(HP)感染、克拉霉素敏感性和宿主CYP2C19基因代谢型方法的准确性,旨在寻求一种方便、快速、准确检测儿童HP感染,克拉霉素敏感性和CYP2C19基因代谢型的方法。方法选取2013年7月至2014年11月北京儿童医院消化科123例13C呼气试验检查阳性的胃炎或消化性溃疡患儿进行电子胃镜检查,胃镜下取胃黏膜并收集胃液标本。从胃液中提取DNA,然后通过聚合酶链式反应(PCR)扩增Rnase P酶和cag H以检测幽门螺旋杆菌的存在。通过PCR限制性片段长度多态性(PCR-RFLP)分别检测HP23SrRNA和宿主CYP2C19基因代谢型。研究共利用5对引物和9条探针进行HPcag H基因和23SrRNA基因,以及人Rnase P基因和CYP2C19*2、CYP2C19*3基因检测。将胃液结果与胃黏膜活检标本HP培养和E-test药敏试验及CYP2C19基因代谢型检测结果进行比较分析。结果以胃黏膜HP培养、E-test药敏试验及CYP2C19基因代谢型检测结果为金标准,胃液实时PCR检测HP感染诊断敏感度为100%...     

Recurrent abdominal pain and Helicobacter pylori in a community-based sample of London children

Helicobacter pylori is accepted as an important factor in the pathogenesis of peptic ulcer disease. Infection is probably most commonly acquired in early life but there is still limited information on the prevalence or symptomatology of H. pylori infection in childhood. The aim of the present study was to establish the prevalence of H. pylori infection in a large sample of urban school children and to determine its relationship, if any, to a history of recurrent abdominal pain. Using a commercial ELISA significant levels of anti- H , pylori IgG antibody were detected in 107/640 (16.7%) of school children (M, 383; F, 257; mean age 9.15 years, range 4-13). No relationship was demonstrated between H. pylori seropositivity and a personal or family history of recurrent abdominal pain or the nature of the pain.     

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。     

The prevalence of Helicobacter pylori serum antibodies in children with recurrent abdominal pain

As part of a large, prospective study we investigated the prevalence Helicobacter pylori serum antibodies in children with recurrent abdominal pain (RAP). All patients suffered from recurrent bouts of abdominal pain for at least 6 months and ranged in age from 6 to 12 years. H. pylori antibodies were detected using an enzyme-linked immunosorbent assay. The prevalence of H. pylori antibodies in the RAP group was compared to that of a control group which consisted predominantly of pre-operative children. None of the control group suffered or had suffered from RAP. Antibodies to H. pylori were found in 7 of 82 (8.5%) RAP patients and in 2 of 39 (5.1%) control children. The latter difference is not significant and suggests that RAP is only rarely caused in children by H. pylori infection.     

Recurrent abdominal pain of gastro-intestinal origin

A consecutive series of 71 children (mean age 8.6 years) with recurrent abdominal pain underwent endoscopic oesophageal, gastric and duodenal biopsy in order to determine whether the pain was of gastro-intestinal origin. Of these 71 children, 27 (38%) showed oesophagitis, 14 (20%) cardiac gastritis, 29 (41%) body gastritis, 38 (54%) antral gastritis, and 29 (41%) duodenitis. Thus, 66 of the 71 children studied had an inflammatory lesion explaining their complaints. One of the patients had a gastric ulcer.Helicobacter pylori colonisation was found in 5 of the children: One hadH. pylori associated antral and body gastritis and 4H. pylori associated antral gastritis only. Body gastritis withoutH. pylori was present in three of these four children. Our data do not support the widespread assumption that recurrent abdominal pain for which no medical cause can be found, is psychogenic; neither do they establish an association betweenH. pylori antral gastritis and recurrent abdominal pain. However, our data provide strong evidence that there is a gastro-intestinal origin of these patients' complaints.Presented in part at the Second Pan Pacific Congress of Paediatric Gastroenterology and Nutrition and First Oceanic Symposium on Paediatric Liver Transplantation. Cairns, Queensland, Australia, 24 August, 1990     

Migraine of gastrointestinal origin

A consecutive series of 31 children (median age 12 years) suffering from migraine with (n=21) or without (n=10) aura underwent endoscopic oesophageal, gastric and duodenal biopsy in order to determine whether the complaints were of gastro-intestinal origin. Of these 31 children, 13 (41.9%) showed oesophagitis, 16 (51.6%) gastritis of corpus, 12 (38.7%) antral gastritis and 27 (87.1%) duodenitis. Thus, 29 of the 31 children studied had an underlying inflammatory lesion explaining their complaints.Helicobacter pylori colonization was found in 7 of the children: one hadH. pylori associated antral and corporal gastritis and 6H. pylori associated antral gastritis only. Gastritis of corpus withoutH. pylori was present in all these 6 children. Our data do not support thatH. pylori is a primary pathogen of inflammatory changes seen in children studied, neither do they establish an association betweenH. pylori, antral gastritis and migraine. However, our data strongly suggest that there is a gastro-intestinal origin of these patients' complaints.Conclusion Our findings provide further evidence that recurrent abdominal pain is an early expression of migraine and strongly support a causal link between recurrent abdominal pain and migraine.     

幽门螺杆菌感染与儿童功能性消化不良的关系

目的探讨幽门螺杆菌(H.pylori)感染对功能性消化不良(FD)儿童症状、病理及胃排空的影响。方法FD儿童110例,H.pylori阴性组30例,H.pylori阳性组80例,H.pylori阳性组按不同的治疗方案分A组(吗丁啉组)30例,B组(H.pylori根除 吗丁啉治疗后复查H.pylori转阴者)42例。比较各组症状积分、胃窦粘膜病理积分和胃液体排空情况。结果H.pylori阳性组饱胀和食欲下降症状重于阴性组(P<0.05),根除H.pylori后上述症状明显改善。H.pylori阳性组胃窦液体排空慢于阴性组,根除H.pylori后排空加快(P<0.05)。结论H.pylori感染是FD患儿的致病因素之一,H.pylori感染可能影响FD儿童的胃排空,根除H.pylori可改善胃排空从而减轻临床症状。     

Helicobacter pylori in children: an Indian perspective

Helicobacter pylori is causally associated with peptic ulcer disease and gastric carcinoma. Typically children get infected with this organism during the first decade of life but diseases, associated with H. pylori, are seen mainly in adults. In India, almost 80% of population is infected with H. pylori and most of them by 10 years of age. Hence, it is important for a pediatrician to know when to suspect this infection, how to investigate and how to treat it. Extensive electronic (PubMed) literature search was done for this review and literature (randomized controlled trials, clinical trials, meta-analysis, practice guidelines) related to H. pylori in children were reviewed. Special emphasis was given to Indian studies. From this review we can conclude that H. pylori infection is very common in Indian children especially in the low socioeconomic status but most infected children remain asymptomatic through out their childhood and about 15% develop peptic ulcer disease as young adults and 1% develop gastric cancer in older age. There is no association, what so ever, of H. pylori infection and recurrent abdominal pain (RAP). Endoscopy is the preferred method of investigation in children with upper digestive symptoms suggestive of organic disease. Children with H. pylori related disease (peptic ulcer, primary gastric B-cell lymphoma and atrophic gastritis with intestinal metaplasia) but not mere H. pylori infection should be treated with the triple drug regimen comprising of proton pump inhibitor (PPI) and two antibiotics for two weeks.     

Helicobacter pylori infection and peptic ulcer in eastern Turkish children: is it more common than known?

Helicobacter pylori (H. pylori) infection is mainly acquired in childhood and is frequent in developing countries. The infection is associated with chronic gastritis in all infected children, but peptic ulcer disease develops in a small number of them. In our country, H. pylori infection and associated peptic ulcer disease are common. In eastern Turkey, we found peptic ulcer disease in 13.2% of children who underwent endoscopic examination. Peptic ulcers were mostly gastric ulcers and H. pylori-positive in the studied population, and most of the children were admitted due to abdominal pain. As there are no well-established criteria leading directly to diagnosis, pediatricians should include H. pylori infection and peptic ulcer disease in the differential diagnosis list when evaluating children with abdominal pain, failure to thrive and upper gastrointestinal system bleeding.