Functional gastrointestinal disorders in children from low socio-economic status and Helicobacter pylori infection.

BACKGROUND: Most studies on functional gastrointestinal disorders (FGIDs) in children are based on data from the northern hemisphere. Scientific reports are arising in South American population, but little is still known about children from low socio-economic status (SES), where Helicobacter pylori infection is endemic. Our objective was to evaluate the prevalence of FGIDs in school children from low SES and its relationship with H. pylori infection. METHODS: Children from 3 public schools of low SES from Santiago de Chile were included. Students completed the Rome III Questionnaire and a survey about other symptoms. Also, the 13 C urea breath test determined the presence of H. pylori infection. RESULTS: Five hundred six children were included, where 48% were male, with a median age of 15.7 years (range 7.1-19.6). Forty-two percent had some FGID, aerophagia and functional constipation being the most frequent. Females (adjusted OR 1.5, 95% CI [1.1, 2.2]), those children with parents within the lowest level of education (adjusted OR 1.6, 95% CI: 1.1-2.4), and family history of gastric cancer (adjusted OR 1.9, 95% CI: 1.2-3.1) were related to FGIDs. The prevalence of H. pylori infection was 55.9% (95% CI [50.7, 60.9]). In multivariable analysis, the presence of abdominal pain (OR 1.55, 95% CI [1.02, 2.36]), but not FGIDs, was related to H. pylori infection. CONCLUSIONS: FGIDs are common in low SES students. A low educational level of the household head, family history of gastric cancer. and being female are related to the development of FGIDs. In this study, no relationship between the presence of H. pylori and FGIDs was found.

Helicobacter pylori infection is associated with an altered gastric microbiota in children.

The intestinal microbiome in early life influences development of the mucosal immune system and predisposition to certain diseases. Because less is known about the microbiome in the stomach and its relationship to disease, we characterized the microbiota in the stomachs of 86 children and adults and the impact of Helicobacter pylori infection on the bacterial communities. The overall composition of the gastric microbiota in children and adults without H. pylori infection was similar, with minor differences in only low abundance taxa. However, the gastric microbiota in H. pylori-infected children, but not infected adults, differed significantly in the proportions of multiple high abundance taxa compared with their non-infected peers. The stomachs of H. pylori-infected children also harbored more diverse microbiota, smaller abundance of Firmicutes, and larger abundance of non-Helicobacter Proteobacteria and several lower taxonomic groups than stomachs of H. pylori-infected adults. Children with restructured gastric microbiota had higher levels of FOXP3, IL10, and TGFß expression, consistent with increased T-regulatory cell responses, compared with non-infected children and H. pylori-infected adults. The gastric commensal bacteria in children are altered during H. pylori infection in parallel with more tolerogenic gastric mucosae, potentially contributing to the reduced gastric disease characteristic of H. pylori-infected children.

Human gastric epithelial cells contribute to gastric immune regulation by providing retinoic acid to dendritic cells.

Despite the high prevalence of chronic gastritis caused by Helicobacter pylori, the gastric mucosa has received little investigative attention as a unique immune environment. Here, we analyzed whether retinoic acid (RA), an important homeostatic factor in the small intestinal mucosa, also contributes to gastric immune regulation. We report that human gastric tissue contains high levels of the RA precursor molecule retinol (ROL), and that gastric epithelial cells express both RA biosynthesis genes and RA response genes, indicative of active RA biosynthesis. Moreover, primary gastric epithelial cells cultured in the presence of ROL synthesized RA in vitro and induced RA biosynthesis in co-cultured monocytes through an RA-dependent mechanism, suggesting that gastric epithelial cells may also confer the ability to generate RA on gastric dendritic cells (DCs). Indeed, DCs purified from gastric mucosa had similar levels of aldehyde dehydrogenase activity and RA biosynthesis gene expression as small intestinal DCs, although gastric DCs lacked CD103. In H. pylori-infected gastric mucosa, gastric RA biosynthesis gene expression was severely disrupted, which may lead to reduced RA signaling and thus contribute to disease progression. Collectively, our results support a critical role for RA in human gastric immune regulation.

Beliefs about chlamydia testing amongst young people living in relatively deprived areas.

BACKGROUND: This study uses the theory of planned behaviour (TPB) as a framework to investigate salient beliefs about chlamydia testing, amongst young people living in relatively deprived areas. These beliefs may form targets for intervention to increase testing in this high-risk population. METHODS: Participants recruited from colleges in deprived areas of a UK city, completed open-ended questions designed to elicit salient beliefs. Responses were content analysed and categorized as describing behavioural, normative or control beliefs. RESULTS: Beliefs were elicited from 128 respondents (51% male; median age = 17). The commonest behavioural belief, which could have a positive or negative impact on screening intentions, was that testing provides information about health status. Partners were referred to most commonly amongst the normative beliefs. Practical aspects and concerns about social implications of testing were common control beliefs. References to several negative emotions emerged throughout. CONCLUSIONS: This study indicates that raising awareness of chlamydia as a serious sexual health problem may not be the best way to increase the uptake of testing in a high-risk population. Promoting chlamydia testing as potentially providing reassurance may be an alternative. It may also be important to reduce perceptions of social disapproval as well as negative emotion regarding chlamydia testing.

Large mitochondrial DNA deletion in an infant with addison disease.

BACKGROUND: Mitochondrial diseases are a group of disorders caused by mutations in nuclear DNA or mitochondrial DNA, usually involving multiple organ systems. Primary adrenal insufficiency due to mitochondrial disease is extremely infrequent and has been reported in association with mitochondrial DNA deletion syndromes such as Kearns-Sayre syndrome. AIM: To report a 3-year-old boy with Addison disease, congenital glaucoma, chronic pancreatitis, and mitochondrial myopathy due to large mitochondrial DNA deletion. METHOD: Molecular analysis of mitochondrial DNA samples obtained from peripheral blood, oral mucosa, and muscle tissue. RESULTS: A novel large mitochondrial DNA deletion of 7,372bp was identified involving almost all genes on the big arch of mtDNA. CONCLUSIONS: This case reaffirms the association of adrenal insufficiency and mitochondrial DNA deletions and presents new evidence that glaucoma is another manifestation of mitochondrial diseases. Due to the genetic and clinical heterogeneity of mitochondrial disorders, molecular analysis is crucial to confirm diagnosis and to allow accurate genetic counseling.

Plasma potential and energy spread determination using ion beams extracted from an electron cyclotron resonance source.

We have obtained estimates of plasma potentials and energy spreads characterizing an electron cyclotron resonance ion source plasma under different source conditions. Our estimates are obtained from analysis of ion beams extracted from the ion source at 10 kV that are subsequently decelerated into a floating surface scattering chamber where their current intensity incident on a solid sample is measured as function of retardation voltage. The deceleration occurs outside the measurement chamber, permitting beam current measurements in a field-free region. Absence of grids in the deceleration section avoids potential issues of field penetration. The behavior of our deceleration optics was modeled with SIMION. The simulation indicated a linear beam attenuation dependence close to full retardation where the beam current goes to zero. Deviations from this linear dependence observed close to zero beam energy give information on the initial energy spread of the ions extracted from the source. Our decelerated beams measurements are compared with recent in situ probe results and external beams results based on magnetic analysis.

Helicobacter pylori-induced mucosal inflammation is Th1 mediated and exacerbated in IL-4, but not IFN-gamma, gene-deficient mice.

To elucidate the pathogenesis of Helicobacter pylori-associated gastritis, we studied immune responses of C57BL/6J wild-type (WT), SCID, and gene deficient (IFN-gamma-/- and IL-4-/-) mice following infection with a pathogenic isolate of H. pylori (SPM326). During early infection in WT mice, mononuclear and polymorphonuclear cells accumulated in the gastric lamina propria, and the numbers of cells in the inflamed mucosa expressing IFN-gamma, but not IL-4, mRNA rose significantly (p < 0.005), consistent with a local Th1 response. Splenic T cells from the same infected WT mice produced high levels of IFN-gamma, no detectable IL-4, and low amounts of IL-10 following in vitro H. pylori urease stimulation, reflecting a systemic Th1 response. Infected C57BL/6J SCID mice did not develop gastric inflammation despite colonization by many bacteria. Infected C57BL/10J and BALB/c mice also did not develop gastric inflammation and displayed a mixed Th1/Th2 splenic cytokine profile. These data imply a major role for the Th1 cytokine IFN-gamma in H. pylori-associated gastric inflammation in C57BL/6J mice. Compared with WT animals, infected IL-4-/- animals had more severe gastritis and higher levels of IFN-gamma production by urease-stimulated splenocytes (p < 0.01), whereas IFN-gamma-/- mice exhibited no gastric inflammation and higher levels of IL-4 production by stimulated splenocytes. These findings establish C57BL/6J mice as an important model for H. pylori infection and demonstrate that up-regulated production of IFN-gamma, in the absence of the opposing effects of IL-4 (and possibly IL-10), plays a pivotal role in promoting H. pylori-induced mucosal inflammation.

Inflammatory cytokine mRNA expression during early and persistent Helicobacter pylori infection in nonhuman primates.

The role of mononuclear phagocytes in orchestrating the host responses to Helicobacter pylori is inadequately understood. Therefore, gene expression for the monocyte/macrophage-derived cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha was determined before and during H. pylori infection of rhesus monkeys by use of a highly sensitive quantitative reverse transcriptase polymerase chain reaction. The numbers of molecules of IL-1beta, IL-6, and TNF-alpha mRNA in gastric tissue during early infection (7 weeks) significantly exceeded the preinfection numbers (P<.03). Moreover, the numbers of IL-1beta, IL-6, and TNF-alpha mRNA molecules in persistently infected animals (6 years) also were elevated compared with preinfection numbers (P<.02, P=.03, P=.16, respectively). Cytokine gene expression coincided with progressive H. pylori gastritis, confirmed by increased gastritis scores over preinfection scores (P<.005). These findings provide quantitative evidence that H. pylori induces local gene expression of monocyte/macrophage-derived inflammatory cytokines and evokes an innate response in gastric tissue of nonhuman primates.

A comprehensive review of the natural history of Helicobacter pylori infection in children.

Across populations of children, Helicobacter pylori prevalence ranges from under 10% to over 80%. Low prevalence occurs in the U.S., Canada, and northern and western Europe; high prevalence occurs in India, Africa, Latin America, and eastern Europe. Risk factors include socioeconomic status, household crowding, ethnicity, migration from high prevalence regions, and infection status of family members. H. pylori infection is not associated with specific symptoms in children; however, it is consistently associated with antral gastritis, although its clinical significance is unclear. Duodenal ulcers associated with H. pylori are seldom seen in children under 10 years of age. H. pylori-infected children demonstrate a chronic, macrophagic, and monocytic inflammatory cell infiltrate and a lack of neutrophils, as compared with the response observed in adults. The effect of H. pylori infection on acid secretion in children remains poorly defined. The events that occur during H. pylori colonization in children should be studied more thoroughly and should include urease activity, motility, chemotaxis, adherence, and downregulation of the host response. The importance of virulence determinants described as relevant for disease during H. pylori infection has not been extensively studied in children. Highly sensitive and specific methods for the detection of H. pylori in children are needed, especially in younger pediatric populations in which colonization is in its early phases. Criteria for the use of eradication treatment in H. pylori-infected children need to be established. Multicenter pediatric studies should focus on the identification of risk factors, which can be used as prognostic indicators for the development of gastroduodenal disease later in life.

Recombinant Helicobacter pylori urease activates primary mucosal macrophages.

Helicobacter pylori urease is absorbed into the gastric mucosa at sites of inflammation, but whether the enzyme activates mucosal macrophages is not known. Because mucosal macrophages differ phenotypically and functionally from blood monocytes, whether recombinant H. pylori urease (rUrease) activated purified lamina propria macrophages in vitro was investigated. rUrease (1-10 microgram/mL) induced primary mucosal macrophages to produce interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha but not IL-8 proteins in a dose-dependent manner (P<.05 to P<.001). Quantitative reverse transcriptase-polymerase chain reaction using capillary electrophoresis laser-induced fluorescence showed that rUrease (0.1-10 microgram/mL) also induced dose-dependent expression of IL-1beta, IL-6, and TNF-alpha but not IL-8 mRNA (P<.05), suggesting that rUrease-induced production of certain cytokines is regulated at the level of gene transcription. These findings indicate that the ability of H. pylori urease to activate mucosal macrophages, resulting in production of proinflammatory cytokines, may be involved in the pathogenesis of H. pylori-associated mucosal inflammation.

High mucosal levels of tumor necrosis factor alpha messenger RNA in AIDS-associated cytomegalovirus-induced esophagitis.

BACKGROUND & AIMS: To evaluate the role of tumor necrosis factor alpha (TNF-alpha), a key inflammatory cytokine, in cytomegalovirus-associated gastrointestinal disease, we quantitated the level of TNF-alpha messenger RNA (mRNA) in esophageal mucosa from patients with cytomegalovirus-associated esophagitis and acquired immunodeficiency syndrome. METHODS: Four patients underwent endoscopic biopsy of their cytomegalovirus-associated esophageal ulcers before and after ganciclovir therapy. The level of TNF-alpha mRNA in coded esophageal specimens was assessed by in situ hybridization, reverse-transcription polymerase chain reaction, and quantitative polymerase chain reaction. RESULTS: Esophageal mucosa from 3 patients whose ulcers healed or markedly improved contained before therapy numerous macrophages expressing TNF-alpha mRNA and high tissue levels of TNF-alpha mRNA that decreased substantially or were not detectable after therapy. In contrast, esophageal specimens from the single patient whose ulcer worsened after therapy contained many mucosal macrophages expressing TNF-alpha mRNA before as well as after therapy, and the high number of molecules of TNF-alpha mRNA present in the tissue before therapy increased further after treatment. CONCLUSIONS: Increased macrophage production and high tissue levels of TNF-alpha mRNA are associated with cytomegalovirus-associated esophageal ulcers and probably contribute to the inflammatory response associated with cytomegalovirus-induced gastrointestinal disease.

Helicobacter pylori cytotoxin induces vacuolation of primary human mucosal epithelial cells.

We investigated whether Helicobacter pylori cytotoxin induces vacuolation in primary epithelial cells from normal human mucosa. Epithelial cells purified by enzyme digestion and elutriation were evaluated for vacuolation in a blinded protocol by light and electron microscopy before and after incubation with culture supernatant (CS) from H. pylori 60190, which has vacuolating activity for HeLa cells (Tox+), and isogenic H. pylori mutant 60190-v1, which lacks this activity (Tox-). Primary epithelial cells (>98% pure) exposed to CS from Tox+ H. pylori exhibited marked vacuolation (52% +/- 5% of cells) compared with epithelial cells exposed to either CS from Tox- H. pylori (23% +/- 3.2%) or uninoculated control broth (23% +/- 3.7%) (P < 0.05) by light microscopy, which was confirmed by electron microscopy and antibody inhibition studies. These are the first data to show that H. pylori cytotoxin causes vacuolation of primary human mucosal epithelial cells.

Helicobacter pylori urease is a potent stimulus of mononuclear phagocyte activation and inflammatory cytokine production.

BACKGROUND & AIMS: Helicobacter pylori surface proteins induce the production of proinflammatory mediators by mononuclear phagocytes, but the protein responsible for this stimulation has not been identified. This study determined whether urease, the major component of the soluble proteins extracted from H. pylori grown in culture, activates mononuclear phagocytes and stimulates them to produce proinflammatory cytokines. METHODS: Primary human blood monocytes were incubated with column-purified H. pylori urease and assayed by flow cytometry, Immunoassay, and reverse-transcription polymerase chain reaction for phenotypic, functional, and molecular evidence of activation. RESULTS: H. pylori urease induced monocyte expression of surface interleukin 2 receptors and increased expression of HLA-DR, phenotypic changes consistent with activation. Urease also stimulated dose-dependent production of interleukin 1 beta, interleukin 6, interleukin 8, and tumor necrosis factor alpha peptides and messenger RNA. These urease-induced phenotypic and functional changes were inhibited by preincubation of the urease with antisera to H. pylori whole bacteria, purified urease, or the 31-kilodalton subunit of urease. CONCLUSIONS: Among the soluble proteins released by H. pylori, urease is capable of activating monocytes for proinflammatory cytokines production. The local production of cytokines by urease-stimulated mononuclear phagocytes may play a central role in the development of H. pylori gastroduodenal inflammation.

Impact of intestinal lengthening on the nutritional outcome for children with short bowel syndrome.

Survival among children with short bowel syndrome has increased with the use of supportive nutritional techniques including parenteral and enteral nutrition. Further improvement in outcome has been sought by using intestinal lengthening procedures to lengthen the bowel, improve intestinal motility, initiate a progressive increase in intestinal mucosal mass, and thereby improve tolerance to enteral nutrition. The authors examine the growth parameters and the tolerance to enteral nutrition in children with refractory short bowel syndrome before and after intestinal lengthening procedures. For seven children, the percentage of calories from enteral nutrition, the medical and surgical complications, and the number of days in the hospital (1 year before and 2 years after the lengthening procedure) were evaluated. The mean birth weight was 1,991 g (range, 1,198 to 3,096 g). The initial diagnoses requiring bowel resection included necrotizing enterocolitis, multiple small bowel atresias, gastroschisis with midgut volvulus, cloacal exstrophy, and long-segment Hirschsprung's disease. The mean length of the residual small bowel was 49 cm (range, 6 to 92 cm). All but one child had surgical resection of the ileocecal valve. The percentage of enteral nutrition calories significantly increased by 9 months after the procedure (P < .008, analysis of variance). Only one child has been completely weaned from parenteral nutrition. All children's growth parameters have been maintained or improved (weight/age, height/age, and weight/height). Few major medical and surgical complications have been observed. Central venous catheter infection has been the most common medical complication. The mean number of hospitalization days decreased during the second year after the lengthening procedure. The authors conclude that the intestinal lengthening procedure enhances the tolerance for enteral nutrition, improves the nutritional status, and decreases the need for hospitalization. The procedure should be considered for children with refractory short bowel syndrome who require prolonged parenteral nutrition.

The impact of culture on human and space development--new millennial challenge.

The Space Age is causing new applications to the concept of culture, a human coping tool. The exploration and exploitation of outer space resources are altering human culture both on Earth and in orbit. For the first time in history, our species need not merely react and adapt to environment, but plan for a space culture appropriate for extraterrestrial migration. The impact of culture can be analyzed in terms of how space developments alter human perceptions and behavior on this planet; the emergence of a new culture to suit the orbital environment; the organizations that build spacecraft and deploy people aloft; and the technological systems created for spacefaring. This article presents a paradigm for analyzing some of the non-technical human factors involved in space undertakings. It also offers a method for classifying a culture according to ten categories which may be applied both to a macroculture, such as a lunar base; or a microculture, such as a space agency or crew. Human enterprise in space is viewed as both altering the species, and providing a challenge for expanded behavioral and biological scientific research on living and working in space.

Nutrition components and assessment procedures of a university employee wellness program: a case study.

This article describes the various nutrition components and data collection tools developed and implemented within the Montana State University Employee Wellness Program. Nutrition components included a variety of classes, seminars, follow-up support groups, and individual consultations. Tools included surveys and computerized data input cards. It is important for dietetic professionals to initiate the development and implementation of a quality nutrition component within university employee wellness programs.