Abstract: AIMS: The main aim of this study was to assess the nutritional status of children with newly diagnosed Coeliac disease (CD)with comparison to matched controls. A further aim was to assess relationships between presentation patterns and nutrition in childhood CD. METHODS: The nutritional status of newly diagnosed CD was assessed by anthropometry, Bioelectrical Impedance and serum leptin levels, and contrasted to age and gender matched controls. RESULTS: Twenty-five children with CD (mean age of 8.2 +/- 4.5 years) and 25 control children (mean age 8.1 +/- 4.4.) were enrolled. Thirteen (52%) children with CD had gastrointestinal symptoms with 14 having a family history of CD. At presentation 8.7% were wasted, 4.2% were stunted and 20.8% overweight, although none were obese. Mean height and weight for age, other nutritional parameters and serum leptin did not differ between the groups. Serum leptin correlated with BMI in both groups. CONCLUSIONS: Children with CD more commonly present with atypical symptoms than with classical features. Variations in nutrition (under to overnutrition) may be seen at diagnosis, without relationship to the presence of symptoms. Leptin levels were not altered specifically in the setting of CD. Nutritional assessment remains important in the assessment and management of CD in children.
Abstract: BACKGROUND: Poor bone acquisition and increased fracture risk are significant complications associated with Crohn's disease (CD). The aim of this study was to determine the effects of 8 weeks of exclusive enteral nutrition (EEN) therapy upon markers of bone turnover in children with newly diagnosed CD. METHODS: Twenty-three children with newly diagnosed CD and 20 controls (without CD) were enrolled. Children with CD were treated with 8 weeks of EEN. Inflammatory markers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, platelets], nutritional markers (height, weight), and bone markers [C-terminal telopeptides of Type-1 collagen (CTX) and bone specific alkaline phosphatase (BAP)] were measured prior to and following therapy. RESULTS: At diagnosis, children with CD had elevated serum CTX (2.967 +/- 0.881 ng/ml) compared to controls (2.059 +/- 0.568 ng/ml; P = 0.0003). Following the period of EEN, CTX levels fell significantly (2.260 +/- 0.547 ng/ml; P = 0.002), while serum BAP levels (51.24 +/- 31.31 microg/L at diagnosis; control serum BAP = 66.80 +/- 23.23 microg/L; P = 0.07) increased significantly (64.82 +/- 30.51 microg/L; P = 0.02), with both normalizing to control levels. CONCLUSIONS: As well as reducing inflammation, decreasing disease activity, and improving nutrition in children with newly diagnosed CD, EEN therapy also normalized serum markers of bone turnover, suggesting an improvement in bone health. Further investigations of short- and long-term effects of EEN on bone density and overall bone health are now required.
Abstract: BACKGROUND: Campylobacter concisus and other members of the Campylobacter genus have recently been suggested as possible etiological agents of Crohn's disease (CD). To further investigate this issue we determined the prevalence of these organisms in pediatric patients newly diagnosed with CD. METHODS: DNA was extracted from fecal specimens collected from 54 children with CD, 27 noninflammatory bowel disease (non-IBD), and 33 healthy controls and subjected to polymerase chain reaction (PCR) sequencing. RESULTS: Detection of C. concisus DNA using a newly developed PCR assay targeting the 16S rRNA gene of C. concisus showed that 65% (35/54) of fecal samples from CD children were positive, a prevalence significantly higher than that in the healthy (33%, 11/33, P = 0.008) and non-IBD controls (37%, 10/27, P = 0.03). The prevalence of all Campylobacter DNA using genus-specific primers in children with CD was 72% (39/54), which was significantly higher than the 30% (10/33, P = 0.0002) and 30% (8/27, P = 0.0003) observed in healthy and non-IBD controls, respectively. CONCLUSIONS: Given the strengthening evidence for a significantly higher prevalence of C. concisus and other non-jejuni Campylobacter species in pediatric CD, investigation into the role of these non-jejuni Campylobacter species in the initiation of human IBD is clearly a priority.
Abstract: Crohn's disease and ulcerative colitis are lifelong conditions with particular effects upon nutrition, especially in children and adolescents. Various therapies are available for these conditions but there remains no cure. Over the last decades, exclusive enteral nutrition (EEN) has been demonstrated to have efficacy in the induction of remission, along with numerous other nutritional and inflammatory benefits. This article reviews the benefits and outcomes associated with EEN in Crohn's disease. The potential mechanisms of this therapy are highlighted, along with factors that are barriers to the wider use of EEN.
Abstract: BACKGROUND AND AIMS: Various markers are used to monitor disease activity in paediatric Crohn's disease (CD). We sought to determine whether C-reactive protein measurement was useful in the assessment of disease activity in children with CD, with comparison to the other markers of disease activity. METHODS: Details of disease activity, C-reactive protein and inflammatory markers were obtained retrospectively from the records of 100 outpatient visits by 63 children with CD. RESULTS: The children were 12.6 (+/-3.4) years of age. C-reactive protein values correlated positively with disease activity (P < 0.0001). Children with inactive disease (according to pediatric CD activity index scores) had significantly lower C-reactive protein values compared to children with mild disease (P < 0.001). In addition, C-reactive protein values correlated well with ESR (P < 0.0001). Conclusions C-reactive protein measurements provided useful information in assessing children with CD and correlated well with a validated measure of disease activity.
Abstract: BACKGROUND & AIMS: In a prospective study of children with severe ulcerative colitis (UC), we aimed to assess outcomes and to identify predictors of nonresponse to intravenous corticosteroids. METHODS: A total of 128 children (47% males; 12.9 +/- 3.9 y) hospitalized for severe UC were enrolled from 10 pediatric centers. Clinical and laboratory data and the Pediatric UC Activity Index (PUCAI) were recorded throughout the admission. Patients were followed up for 1 year postdischarge. RESULTS: Thirty-seven (29%; 95% confidence interval [CI], 22%-37%) children failed intravenous corticosteroids and received, within 10.5 +/- 6.4 days, cyclosporine (n = 1; 3%), colectomy (n = 3; 8%), or infliximab (n = 33; 89%). Several predictors were associated with intravenous corticosteroids failure, but the best model included number of stools, amount of blood, age, and new-onset disease (odds ratio [OR], 1.9; 95% CI, 1.1-3.5; OR, 2.5; 95% CI, 1.3-4.6; OR, 1.2; 95% CI, 1.04-1.36; and OR, 0.27; 95% CI, 0.1-0.7, respectively). The PUCAI, followed closely by the Travis rule, strongly predicted response when compared with other measures (Seo and Lindgren indices, C-reactive protein level, and fecal calprotectin level) (P < .001). Aiming for sensitivity on day 3, a PUCAI greater than 45 screened for patients likely to fail intravenous corticosteroids (negative predictive value, 94%; positive predictive value, 43%; P < .001). Aiming for specificity on day 5, a PUCAI score greater than 70 optimally guided implementation of salvage therapy (positive predictive value, 100%; negative predictive value, 79%; P < .001). Twenty-five of 33 children treated with infliximab responded. The overall cumulative colectomy rate was 9% and 19% by discharge and 1-year, respectively. The day 3 PUCAI score predicted response up to 1 year postdischarge (P < .001; time to salvage therapy). CONCLUSIONS: The PUCAI, calculated on days 3 and 5 of steroid therapy, can identify patients requiring salvage therapy. Infliximab is an effective therapy in steroid-refractory pediatric UC.
Abstract: In this article, we examine the current and increasing emphasis on accountability and patient safety in health care, focusing on practices of incident reporting and management in New South Wales, Australia. We describe the frames of accountability associated with an incident reporting system, and explore how this system manifests in practice. In contrast to literature that situates incident reporting and local practices as oppositional, we used ethnographic methods to observe the incident management practices of clinical staff in a hospital, and found evidence to characterize this relationship differently. We found that accountability has multiple conceptualizations, and we present three findings that demonstrate how the reporting system and incident management policy are interwoven with local enactments of accountability. We suggest that systematic efforts toward improvement cannot be divorced from the local context, and emphasize the importance of local ecologies of practice in facilitating the meaningful utilization of such incident reporting systems.
Abstract: BACKGROUND AND AIM: Infliximab (IFX) is a monoclonal antibody licensed to treat medically refractory Crohn's disease (CD). Our aim was to elucidate the effects of IFX therapy on clinical, growth and serum parameters in children with CD in a single pediatric center in Sydney, Australia. METHODS: A retrospective case series review of children treated with IFX for CD at Sydney Children's Hospital, Australia was undertaken, with a review of outcomes after starting IFX. Main outcome measures were response and remission (as measured according to improvements in Pediatric Crohn's Disease Activity Index scores and Physician Global Assessment), laboratory markers (C-reactive protein, erythrocyte sedimentation rate, hemoglobin, white cell count, lymphocytes, neutrophils, platelets, albumin) and growth (Z scores). RESULTS: The 16 patients included had a mean age at first infusion of 13.0 years (1.25-17.5 years). Six of 12 patients (with adequate data available) were in remission at 2 weeks following the first infusion. At 1 year, 10 of 12 patients (83%) were in remission. Mean C-reactive protein and erythrocyte sedimentation rate had fallen significantly (P < 0.05) at 2 weeks (from 29 to 7 mg/L and 40 to 19 mm/h, respectively). Positive trends were observed for all other parameters, excluding lymphocytes and white cell count. At 1 year, mean Z score for body mass index improved significantly from -0.9 to -0.1 (P < 0.01). CONCLUSIONS: Disease activity subsides in most children treated with IFX for CD. IFX therapy also improves some growth parameters. The pattern of improvement requires further elucidation, as the results in the present study suggest differing dosing frequency of infusion may achieve better efficacy.
Abstract: The presence of Campylobacter concisus in the saliva of healthy individuals and patients with inflammatory bowel disease (IBD) was examined. C. concisus was detected in 97% of the healthy individuals and 100% of the patients with IBD tested. The C. concisus culture positivity rate in younger children was significantly lower than that in the other age groups.
Abstract: The Pediatric Crohn Disease Activity Index (PCDAI) is an established and validated measure of disease activity in children with Crohn disease. However, its use in the research setting can be limited because of ambiguity of the subjective and anthropometric components of the index. Here we propose and evaluate a modified PCDAI (Mod PCDAI) consisting of the laboratory measures of the PCDAI plus C-reactive protein. This Mod PCDAI can provide an indication of disease activity because it correlates with the PCDAI, physicians' global assessment, and fecal calprotectin, and therefore may provide a suitable alternative to the PCDAI when required.
Abstract: Defensins are antimicrobial peptides produced at a variety of epithelial surfaces. In the intestinal tract, they contribute to host immunity and assist in maintaining the balance between protection from pathogens and tolerance to normal flora. However, attenuated expression of defensins compromises host immunity and hence may alter the balance toward inflammation. Altered defensin production is suggested to be an integral element in the pathogenesis of inflammatory bowel disease (IBD). Evidence for this is shown in Crohn's disease where reduced alpha-defensin levels are seen in patients with ileal disease and reduced beta-defensin levels in those with colonic involvement. Further evidence is provided by research linking nucleotide oligomerization domain 2 (NOD2) mutations and deficient defensin expression. However, alternate studies suggest that NOD2 status and defensin expression are independent, and that defensin deficiency is due to mucosal surface destruction as a result of inflammatory changes, indicating that reduced defensin expression is a symptom of the disease and not the cause. Although it is clear that defensin expression is altered in IBD, it is less clear whether defensin deficiency is implicated in the pathogenesis of IBD or is a consequence of the disease process. The aim of this article is to review the current knowledge of defensins in IBD and discuss their potential role in IBD pathogenesis.
Abstract: Approximately 25 % of individuals with Crohn's disease (CD), a life-long relapsing-remitting disease, are diagnosed during childhood and adolescence. Symptoms of CD, including abdominal pain, nausea and diarrhoea, can lead to reduced food intake, which may negatively have an impact on nutritional status during this critical period of growth and development. The aims of the present study were to assess the growth and adequacy of dietary intakes of children with CD at Sydney Children's Hospital, Randwick, and compare with healthy controls. Sixty-three subjects aged 10-16 years were recruited, including: children with active CD (n 18), children with CD in remission (n 23) and healthy controls (n 22). Dietary intake was assessed using a FFQ and compared with current Australian recommended dietary intakes (RDI). Growth and dietary intakes were compared between groups. Subjects with active CD had lower weight and BMI Z scores than children in remission and controls. The energy intakes of children with active CD and those in remission were significantly lower than estimated energy requirements (P = 0.001 and P = 0.03 respectively). Children with active CD did not meet the RDI for Fe and their Ca intake was lower than the RDI (P = 0.04). In conclusion, the dietary intake of children with active CD was impaired, with inadequate intakes of energy, Ca and Fe. Reduced energy intakes during active disease may contribute to poor weight gain and impaired growth. Quantifying nutrient intake and ascertaining requirements for nutritional supplementation are essential components of successful management in paediatric CD.
Abstract: The presence of Campylobacter species other than Campylobacter jejuni and antibodies to Campylobacter concisus in children were investigated. A significantly greater presence of C. concisus and higher levels of antibodies to C. concisus were detected in children with Crohn's disease (CD) than in controls. Campylobacter species other than C. jejuni were isolated from intestinal biopsy specimens of children with CD.
Abstract: Cow's milk protein allergy is a condition commonly managed by general practitioners and paediatricians. The diagnosis is usually made in the first 12 months of life. Management of immediate allergic reactions and anaphylaxis includes the prevention of accidental food ingestion and provision of an adrenaline autoinjector, if appropriate. By contrast, the clinical course of delayed food-allergic manifestations is characterised by chronicity, and is often associated with nutritional or behavioural sequelae. Correct diagnosis of these non-IgE-mediated conditions may be delayed due to a lack of reliable diagnostic markers. This review aims to guide clinicians in the: (i) diagnostic evaluation (skin prick testing or measurement of food-specific serum IgE levels; indications for diagnostic challenges for suspected IgE- and non-IgE-mediated food allergy), (ii) dietary treatment, (iii) assessment of response to treatment, (iv) differential diagnosis and further diagnostic work-up in non-responders, (v) follow-up assessment of tolerance development and (vi) recommendations for further referral.
Abstract: OBJECTIVE: To characterise epidemiological, clinical and laboratory features of children in New South Wales with chronic hepatitis B (HBV) or C (HCV) infections. DESIGN AND SETTING: Retrospective record review of epidemiological, clinical, laboratory, liver biopsy and treatment data for children (aged < 18 years) referred to tertiary referral paediatric and refugee clinics in NSW with chronic HBV or HCV during 2000-2007; and comparison with NSW Health notification data for the same period. MAIN OUTCOME MEASURES: Numbers and characteristics of referred children with HBV and HCV, and notifications to NSW Health. RESULTS: During 2000-2007, 79 children with chronic HBV and 29 with HCV infection were referred to specialist clinics, while 930 children with HBV and 777 with HCV infection were reported to NSW Health. Most of the referred children with HBV were born overseas, while most with HCV were born in Australia to mothers with a history of intravenous drug use. Of the 79 HBV-infected children, 56 were e-antigen positive. Most HCV-infected children (23/29) had alanine aminotransferase levels < or = 2 times the upper limit of normal, and more than half of those who had genotype determined had type 2 or 3. Fibrosis was evident in liver biopsies performed for both HBV and HCV. CONCLUSIONS: Although advanced liver disease was uncommon in children referred with HBV or HCV infection, a large number of infected children in NSW were not referred for specialist medical care, indicating that opportunities to intervene early in the natural history of these infections, particularly HCV, are being missed.
Abstract: OBJECTIVES: Variation in medical care can be a barrier to improving clinical outcomes. We aim to describe the variation in care of Crohn disease as provided by a broad sample of pediatric gastroenterologists. METHODS: Two hundred forty-six Crohn disease patients of 93 pediatric gastroenterologists from 48 practice sites starting treatment with either thiopurine or infliximab were studied. We assessed variation in diagnostic testing that had been performed to establish the diagnosis of Crohn disease and to assess the phenotype, extent, and severity of disease. We also assessed variation in initial thiopurine and infliximab dosage and in nutritional therapy. RESULTS: Diagnostic studies in which care was uniform included complete blood count, performed in 100% of patients, erythrocyte sedimentation rate and colonoscopy in 96%, and upper endoscopy in 89%. However, imaging of the small bowel had not been performed in 19%, and a stool test for pathogens had not been performed in 29%. Thiopurine methyltransferase (TPMT) had been measured in 61% of patients before treatment with a thiopurine; in 85%, TPMT was normal. Nonetheless, even when TPMT was normal, 40% of patients received an initial dose of thiopurine that was lower than recommended. Testing for tuberculosis before initiating treatment with infliximab was not performed in 30%. In addition, 36% of severely underweight patients were not receiving a multivitamin supplement, supplemental formula, or tube feeding. CONCLUSIONS: There is variation in diagnostic and therapeutic interventions in the management of pediatric Crohn disease, and gaps exist between recommended and actual care.
Abstract: Aim: Although available data support a role for exclusive enteral nutrition (EEN) in children with Crohn's disease (CD), use of this therapy varies. The aim of this study was to define the patterns of use of EEN across Australia and to better understand the reasons for this variation. Methods: Using an existing email network, Australian paediatric gastroenterologists were asked to provide details of their attitudes towards, and use of, EEN in children. A questionnaire was designed to direct responses, with regard to use of EEN, to current EEN protocols and patterns of use. Results: Twenty-one replies were received (58% response). Although 12 respondents felt that EEN was an appropriate therapy for CD, only 8 regularly used EEN for their patients. Usage varied between states and within units. Current use was related to practitioners' experiences of EEN during their gastroenterology training. The concerns of those who did not recommend EEN included compliance, cost and resource demands. The doctors who recommend EEN reported that family support, team approach and disease location were important factors for a positive outcome from EEN. Current protocols varied in terms of type of formula, length of therapy and use of concurrent medications. Conclusions: Variations in care were illustrated across these paediatric gastroenterologists. Practitioners have many reasons and concerns about the use of EEN: these impede the wider use of EEN for paediatric CD. More consistent protocols for the use of EEN and an improved understanding of the mechanisms of EEN could lead to enhanced use of this therapy.
Abstract: BACKGROUND AND AIMS: Eosinophilic esophagitis and celiac disease are distinct gastrointestinal disorders. The present study in children highlights the possible coexistence of these two conditions. This study also analyzes the epidemiological and clinical profiles of these patients. METHODS: The medical records of patients diagnosed with celiac disease from 1 April 1999 to 31 March 2007 were reviewed. Patients with coincident histological diagnosis of eosinophilic esophagitis were retrospectively identified. The presenting symptoms, laboratory evaluations, endoscopic and histopathological findings, and treatment and follow-up outcomes of these patients were analyzed. RESULTS: Of the 221 patients with celiac disease, seven (3.2%) were also diagnosed with eosinophilic esophagitis. A majority (6/7) presented with periumbilical pain and diarrhea. None had dysphagia. Each patient had abnormal celiac screening tests. Three patients had peripheral blood eosinophilia and elevated eosinophil cationic protein. Endoscopic changes of eosinophilic esophagitis and celiac disease were apparent in the majority of patients (6/7). A gluten-free diet was instituted in every patient. Topical corticosteroid therapy was started in one patient at diagnosis and in another patient after repeat endoscopic and histopathological evaluations. CONCLUSIONS: Awareness of the potential coexistence of eosinophilic esophagitis and celiac disease should promote optimal diagnosis of these conditions. Routine esophageal biopsies may be warranted when investigating for celiac disease.
Abstract: Three types of infant formula (soy, extensively hydrolysed and amino acid) may be appropriate for treating cows milk protein allergy. Selection of a formula depends on the allergy syndrome to be treated. Extensively hydrolysed formula is recommended as first choice for infants under 6 months of age for treating immediate cows milk allergy (non-anaphylactic), food protein-induced enterocolitis syndrome, atopic eczema, gastrointestinal symptoms and food protein-induced proctocolitis. Soy formula is recommended as first choice for infants over 6 months of age with immediate food reactions, and for those with gastrointestinal symptoms or atopic dermatitis in the absence of failure to thrive. Amino acid formula is recommended as first choice in anaphylaxis and eosinophilic oesophagitis. If treatment with the initial formula is not successful, use of an alternative formula is recommended.
Abstract: BACKGROUND: Fecal calprotectin is a sensitive marker for gut inflammation. Recently, we have established that a related protein, S100A12, is elevated in the feces of children with inflammatory bowel disease (IBD). This may represent a specific and sensitive disease marker. The objective was to investigate the utility of fecal S100A12, in comparison to fecal calprotectin and standard inflammatory markers, as a screening marker for IBD in children with gastrointestinal symptoms. METHODS: Stool samples were obtained from 61 children presenting with gastrointestinal symptoms requiring endoscopy. Fecal S100A12, calprotectin, and serum S100A12 levels were measured and correlated to final diagnosis and standard tests (ESR, CRP, platelet count, and albumin). RESULTS: Children diagnosed with IBD (n = 31) had elevated fecal S100A12 (median 55.2 mg/kg) and calprotectin (median 1265 mg/kg) levels compared with the children without IBD (n = 30; S100A12: median 1.1 mg/kg, P < 0.0001; calprotectin: median 30.5 mg/kg; P < 0.0001). The sensitivity and specificity of fecal S100A12 (cutoff 10 mg/kg) for the detection of IBD were both 97%, whereas fecal calprotectin (cutoff 50 mg/kg) gave a sensitivity of 100% and a specificity of 67%. CONCLUSIONS: Both fecal markers were superior to the sensitivities and specificities of any standard inflammatory test. Both fecal S100A12 and calprotectin are sensitive markers of gastrointestinal inflammation, but fecal S100A12 provided exceptional specificity in distinguishing children with IBD from children without IBD. Fecal S100A12 is a simple, noninvasive test that can be used to screen and select children warranting further invasive and laborious procedures such as endoscopy for the investigation of their gastrointestinal symptoms.
Abstract: BACKGROUND: At least 25% of individuals diagnosed with Crohn's disease (CD) have onset of disease in childhood. Almost all children with CD have nutritional impairments, such as weight loss or stunting, at diagnosis or subsequently. Nutritional therapy (exclusive enteral nutrition) is established as a valid and effective treatment in paediatric CD. The advantages of this approach are induction of remission and control of inflammatory changes, mucosal healing, positive benefits to growth and overall nutritional status, and avoidance of other medical therapies. AIM: To provide a comprehensive up-to-date review of the roles of nutritional therapy in CD and of the data supporting this therapy. METHODS: A search of PubMed was performed with search terms 'enteral nutrition', 'nutritional therapy', 'Crohn disease' and 'children'. Relevant articles were selected from this search. In addition, the reference lists of available articles were reviewed for further relevant articles. RESULTS: Nutritional therapy offers numerous benefits in the management of CD. Recent work has begun to elucidate the likely mechanisms of this therapy. These include direct mucosal anti-inflammatory effects and alteration of intestinal microflora. CONCLUSION: Further studies are required to define longer-term effects of nutritional therapy in patients with CD.
Abstract: Probiotics consist of yeast or bacteria, especially lactic acid bacteria. They are available as capsules, powder, fermented milks or yoghurts. Probiotics exhibit strain-specific differences in their resistance to acid and bile, ability to colonise the gastrointestinal tract, clinical efficacy, and benefits to the health of the host. There is level I evidence for the use of probiotics in treating acute infectious diarrhoea and preventing antibiotic-associated diarrhoea, with Lactobacillus rhamnosus GG and Saccharomyces boulardii having the most evidence to support their use for these conditions. There is level II evidence that S. boulardii combined with high-dose vancomycin is more effective than the antibiotic alone in preventing recurrent Clostridium difficile diarrhoea. There is level I evidence that probiotics prevent traveller's diarrhoea. There is level I evidence for use of the high-potency probiotic VSL#3 in preventing pouchitis, and level II evidence for this agent in preventing relapse in patients with ulcerative colitis. Probiotics are generally regarded as safe and well tolerated. Some probiotics may be contraindicated in patients who are immunocompromised or have severe underlying illness, as they have been reported to cause fungaemia and bacteraemia.
Abstract: BACKGROUND: Interleukin-18 (IL-18) is increased in the inflamed mucosa of patients with Crohn's disease (CD). The balance between this pleiotropic proinflammatory cytokine and its natural inhibitor, IL-18-binding protein (IL-18BP), may contribute to the pathogenesis of inflammatory bowel disease (IBD). METHODS: Serum and mucosal biopsies were collected from children with IBD, from children with celiac disease, and from controls. Biopsies were maintained in culture for 24 hours, and supernatant was collected. Serum and supernatant IL-18 and IL-18BPa concentrations were measured by immunoassay. Disease activity score (PCDAI) and standard serum inflammatory markers (albumin, platelets, ESR, and CRP) were recorded. RESULTS: Serum IL-18 was greater in children with CD (537 pg/mL) than in controls (335 pg/mL; P < 0.05) but not in children with ulcerative colitis (UC) or IBD type unclassified (IBDU). Mucosal IL-18 was greater in children with CD and UC/IBDU than in controls (P < 0.01). Serum IL-18BPa was increased in children with CD compared with that in controls (3.9 versus 2.6 ng/mL; P < 0.05), but was not elevated in children with UC/IBDU. Furthermore, calculated free-serum IL-18 was elevated in CD, but not UC/IBDU, compared with that in controls (P = 0.001). Total and free-serum IL-18 were elevated in severe CD relative to in mild/moderate disease. CONCLUSIONS: IL-18, produced in the colons of children with IBD, may contribute to local inflammatory changes. Systemic IL-18 level may be a useful indicator of gut inflammation. Furthermore, free IL-18 is greatly elevated in children with CD, suggesting that compensatory increases in IL-18BPa are insufficient. Further exploration of the role of this cytokine in the pathogenesis of IBD is now required.
Abstract: With increasing medical knowledge and emphasis upon evidence-based medicine, it is essential for practitioners to have optimal literature searching skills. There are limited data regarding the use of online information retrieval (IR) systems by paediatric junior medical officers (JMO). The aims of this questionnaire-based study of a group of JMO were to assess the accessibility, frequency of use and preferences for electronic information resources, and to ascertain their perceived adequacy of training and expertise in online searching. Questionnaires were distributed to 319 JMO at two Australian children's hospitals. A total of 106 questionnaires were returned (33.2% response rate). Twenty-four-hour access to electronic medical databases was available to almost 90% of respondents at work or home. Five or less online searches per month were performed by 53.7% of respondents. Previous formal training in database searching was reported by 72.4% of respondents, but over half felt it had been inadequate. Most JMO (91.5%) acknowledged a need for further training in search skills. In spite of widespread availability of online resources, use of these resources was sub-optimal in this group of trainee doctors. Most respondents reported a need for further training in electronic searching. Continuing targeted education in electronic database searching is required to ensure that future doctors develop skills to ensure optimal use of medical literature.
Abstract: BACKGROUND: The use of exclusive enteral nutrition to treat paediatric Crohn's disease (CD) is widely accepted, although the precise mechanism(s) of action remains speculative. AIM: To investigate the changes to key intestinal bacterial groups of Eubacteria, Bacteroides, Clostridium coccoides, Clostridium leptum and Bifidobacteria, during and after exclusive enteral nutrition treatment for CD in paediatric patients and correlate these changes to disease activity and intestinal inflammation. METHODS: Stool was collected from six children at diagnosis of CD, during exclusive enteral nutrition and 4 months post-therapy, and from seven healthy control children. The diversity of bacteria was assessed by polymerase chain reaction-denaturing gradient gel electrophoresis with changes to bacterial diversity measured by Bray-Curtis similarity, intestinal inflammation assessed by faecal S100A12 and the disease activity assessed by PCDAI. RESULTS: A significantly greater change in intestinal bacterial composition was seen with exclusive enteral nutrition treatment compared with controls. Further, the intestinal bacteria remained altered 4 months following exclusive enteral nutrition completion. Changes in the composition of Bacteroides were associated with reduced disease activity and inflammation. CONCLUSIONS: Exclusive enteral nutrition reduces bacterial diversity and initiates a sustained modulation of all predominant intestinal bacterial groups. Exclusive enteral nutrition may reduce inflammation through modulating intestinal Bacteroides species. The implications of these results for exclusive enteral nutrition therapy and CD pathogenesis should now be the subject of further investigation.
Abstract: Coeliac disease (CD) screening has progressed rapidly with tissue transglutaminase (TTG), the screening tool of choice. However, TTG may be unreliable in young children and advances in CD etiology understanding have seen improvements in anti-gliadin (AGA) assay technology. The aim of this study was to investigate the utility of an updated and refined AGA (Neogliadin) assay for CD screening in children with gastrointestinal symptoms. Children attending the Sydney Children's Hospital, Randwick, with gastrointestinal symptoms had sera collected and assayed by Neogliadin and commercial TTG assays in addition to the usual clinical work-up. One hundred and fifteen children were recruited in which 32 were diagnosed with CD. AGA-IgA screening by Neogliadin showed improved sensitivity (83%) and specificity (91%) but did not eclipse the sensitivity (93%) and specificity (90%) of TTG-IgA screening. In the children diagnosed with CD, 7 were identified as younger than 5 years of age with 4/7 AGA-IgA positive, 5/7 AGA-IgG positive, and 6/7 TTG-IgA positive. The updated Neogliadin IgA assay does not improve on the accuracy achieved by TTG screening. TTG appears to be a suitable screening tool for children younger than 5 years of age although this preliminary finding requires confirmation.
Abstract: BACKGROUND: Although there is compelling evidence to support the role of bacteria in Crohn's disease (CD), there is currently no solid evidence to support the role of any one specific bacterial causative agent. Recent studies have suggested that members of the Helicobacteraceae may play a role in the development of CD. The aim of this study was to further investigate the presence of members of the Helicobacteraceae in children with and without CD. MATERIALS AND METHODS: Fecal specimens from 29 children with CD, 11 healthy, normal controls, and 26 symptomatic controls with non-inflammatory bowel disease (IBD) pathology were obtained for DNA extraction and subjected to Helicobacteraceae-specific polymerase chain reaction (PCR). All PCR-positive samples were sequenced. The association between the presence of members of the Helicobacteraceae and each study group was statistically analysed using the Fisher's exact test. RESULTS: Based on Helicobacteraceae-specific PCR analysis, 59% (17 of 29) of the children with CD were positive, which was significantly higher than that in asymptomatic healthy children [9% (1 of 11); p = .01] and that in symptomatic children with non-IBD pathology [0% (0/26); p < .0001]. Sequencing of the 16S rRNA gene of positive samples revealed the presence of both enterohepatic Helicobacter species and Helicobacter pylori in fecal specimens. CONCLUSIONS: For the first time, enterohepatic and gastric Helicobacter species have been identified in fecal specimens from children diagnosed with CD using PCR. Our data suggest that Helicobacter species may have a pathogenic role in the development of CD in a considerable proportion of children.
Abstract: The expression of the inflammatory S100 calgranulin proteins (S100A8, S100A9 and S100A12) in normal and Helicobacter pylori-infected gastric mucosa of children were examined. S100A8, S100A9 and S100A12, which were virtually absent in normal gastric mucosa, were highly expressed in H pylori-infected mucosa. This expression correlated with the severity of gastritis (r=0.9422, P<0.05). S100 calgranulins may be involved in bacterial-induced gastritis and may limit bacterial growth.
Abstract: BACKGROUND: Postnatal growth of the small intestine occurs by crypt hyperplasia and by the less recognised mechanism of crypt fission. How the small intestine grows is largely extrapolated from animals and is poorly described in humans. AIM: To investigate crypt fission and crypt hyperplasia as mechanisms of intestinal growth in humans. PATIENTS AND METHODS: Proximal intestinal samples were taken from 3 neonates at surgical anastomosis, and duodenal biopsies were taken at endoscopy from 16 infants (mean age 0.7, range 0.3-1.7 years), 14 children (mean age 7.9, range 2.4-16.2 years), and 39 adults. Morphometric measures of villous area, crypt length (measure of crypt hyperplasia), and percentage of bifid crypts (measure of crypt fission) were assessed by a microdissection technique. RESULTS: Mean crypt fission rates in neonates, infants, children, and adults were 7.8%, 15%, 4.9%, and 1.7%, respectively. In particular, crypt fission peaked at 18% in 5 infants from 6 to 12 months of age. Mean crypt length was 123 microm in neonates, 287 microm in infants, 277 microm in children, and 209 microm in adults. Thus, crypt hyperplasia had a broad peak during infancy and childhood. CONCLUSIONS: We conclude that crypt fission was present predominantly during infancy, and crypt hyperplasia occurred during both infancy and childhood.
Abstract: Probiotics have become increasingly popular and are now promoted as having a wide range of benefits. Probiotics are generally very well tolerated and safe but many of the purported uses are not yet well supported with adequate scientific evidence. Two well-established roles for probiotics in children are acute diarrhoeal illness and antibiotic-associated diarrhoea. This review summarises the evidence supporting probiotics for various gastrointestinal disorders with particular reference to their role in the management of acute diarrhoea and antibiotic-associated diarrhoea in children.
Abstract: BACKGROUND: Measurement of thiopurine metabolite levels may be useful as a clinical tool to optimize thiopurine treatment of paediatric inflammatory bowel disease (IBD). AIM: The authors evaluated correlations between 6-thioguanine nucleotide (6-TGN) and therapeutic response, metabolite levels and drug toxicity. METHODS: Fifty-six paediatric IBD patients treated with thiopurines had 326 metabolite level measurements and were retrospectively reviewed. Clinical status and laboratory parameters were compared with metabolite levels. RESULTS: There was significant correlation between 6-TGN levels and therapeutic response, with higher median 6-TGN levels among patients with therapeutic response than those with non-therapeutic response (194 vs. 146 pmol/8 x 10(8) RBC; P = 0.0004). Patients with 6-TGN levels >235 pmol/8 x 10(8) RBC were more likely to achieve therapeutic response than those below the cut-off (odds ratio, 2.5; 95% CI, 1.5-4.1). Patients who developed leukopenia tended to have higher median 6-TGN levels than those without leukopenia (261 vs. 160 pmol/8 x 10(8) RBC) but the difference was not statistically significant. There was no correlation between 6-methylmercaptopurine levels and hepatotoxicity. Two patients developed acute pancreatitis. Metabolite level measurements were helpful in identifying non-compliance in nine patients. CONCLUSIONS: Monitoring of thiopurine metabolite levels is useful to guide and optimize dosing, as an adjunct to clinical judgement, blood count and liver biochemistry measurements to minimize the risk of drug toxicity and to confirm non-compliance.
Abstract: Exclusive enteral nutrition using polymeric formula (PF) is a well-established therapeutic option for active Crohn's disease; however, its mechanisms of action are unknown. We investigated the anti-inflammatory effects of PF in an in vitro model of epithelial cell inflammation. PF did not affect cell viability over a range of dilutions, but when PF was added to the culture medium the interleukin (IL)-8 response to proinflammatory stimuli was significantly reduced. This effect was due to PF acting directly on the cells as the IL-8 response was still reduced when PF was separated from the proinflammatory stimuli in a 2-compartment system. In the presence of PF, nuclear factor (NF)-kappaB nuclear migration was not inhibited; however, IkappaBalpha degradation was delayed. PF has direct anti-inflammatory effects upon immortalized colonic enterocytes. Therefore PF may, in part, modulate gut inflammation by directly reducing the inflammatory response of the intestinal epithelium.
Abstract: OBJECTIVE: Various markers characterize the complex inflammatory processes seen in chronic inflammatory bowel disease (IBD) including calprotectin, a complex of two S100 proteins, which has been evaluated and validated as a faecal marker of inflammation. However, the systemic and mucosal expression patterns of calprotectin and related S100 proteins are not well characterized in this disease. The objective of this study was to assess serum and mucosal levels of calprotectin, S100A12 and soluble receptor for advanced glycation end products (sRAGE), a putative S100 ligand, in a paediatric population with IBD. MATERIAL AND METHODS: Children were enrolled at diagnosis of IBD, along with groups of children without IBD. Standard inflammatory markers and disease activity scores were collated. Calprotectin, S100A12 and sRAGE levels in serum and biopsy culture supernatants were measured by ELISA and tissue distribution of S100 proteins was investigated by immunohistochemistry. RESULTS: Serum and mucosal calprotectin and S100A12 levels were increased in children with IBD as compared with non-IBD controls. Serum calprotectin levels correlated with S100A12 levels and with disease activity scores in children with IBD. sRAGE levels were not increased in IBD. S100A8, S100A9 and S100A12 were abundantly expressed throughout the lamina propria and epithelium in inflamed mucosa. In contrast, these proteins were present in the lamina propria, but not the epithelium, in non-inflamed mucosa. CONCLUSIONS: Serum calprotectin and S100A12 are increased in children with IBD and indicate disease activity. Elevated levels of these proteins are present in the colonic mucosa and may contribute to the pathogenesis of IBD. Furthermore, an imbalance between sRAGE and S100A12 may contribute to inflammatory changes present in IBD.
Abstract: BACKGROUND: The calcium-binding protein S100A12 is related to calprotectin, a protein shown to be a useful marker of gut inflammation. S100A12 levels are elevated in serum and mucosa of children with inflammatory bowel disease (IBD) and may be implicated in the pathogenesis of IBD. The aims of this study were to validate an immunoassay for the detection of fecal S100A12, to assess its value as a new noninvasive marker of gut inflammation, and to investigate S100A12 levels in feces of children with IBD at diagnosis and during treatment. MATERIALS AND METHODS: Feces were collected from children with active IBD at diagnosis and during treatment for IBD and from normal healthy control subjects. Fecal and serum levels of S100A12 were measured by immunoassay. RESULTS: A sensitivity of 96% and a specificity of 92% were observed when 10 mg/kg fecal S100A12 was used as a cutoff. S100A12 levels were evenly distributed throughout fecal samples and were stable for 7 days when stored at room temperature. Fecal S100A12 was elevated in children with IBD compared with healthy control subjects, with levels closely correlated to disease activity and other serum inflammatory markers, particularly lower gut involvement. Fecal S100A12 levels fell during therapy in children entering remission with normal C-reactive protein levels. CONCLUSIONS: Fecal S100A12 is a novel noninvasive marker that distinguishes children with active IBD from healthy control subjects with high sensitivity and specificity. Fecal S100A12 possesses characteristics that are desirable for a noninvasive disease marker and therefore is a suitable candidate marker for IBD. Further evaluation is required to examine this marker in additional contexts.
Abstract: Crohn's disease and ulcerative colitis (the inflammatory bowel diseases) are two well characterized conditions featuring inflammation of the gastrointestinal tract. Gut inflammation may be detected, assessed and measured by a variety of methods but their utility varies extensively. Over the past decade, calprotectin, belonging to a family of S100 proteins, has been shown to be a reliable marker of gut inflammation that corresponds to neutrophil migration. In addition, other members of the S100 family have important roles in inflammation and may also be useful markers of gut inflammation. Furthermore, these proteins may have functional roles in gut defense or in the pathogenesis of inflammatory bowel disease.
Abstract: BACKGROUND: Exclusive enteral feeding has been shown to be as efficacious as corticosteroids in inducing remission in children with Crohn's disease (CD), with additional nutritional benefits. The use of polymeric formulae provides superior palatability and acceptance over elemental feeds, but polymeric formulae have not been universally adopted. The present retrospective analysis of enteral feeding in children with Crohn's disease aims to demonstrate the short-term benefits of enteral feeding in children upon disease activity and nutrition parameters. METHODS: The case records of children with CD managed with exclusive enteral nutrition (EEN) by a multidisciplinary team over a 2-year period were reviewed. Data relating to therapy, background disease details, and outcome were collated. Primary outcome measures established were weight change and disease activity (Pediatric Crohn's Disease Activity Index: PCDAI). RESULTS: Twenty-seven children received EEN with polymeric formulae. Fifteen children had newly diagnosed CD and 12 had known long-standing CD. Twenty-four children completed the prescribed period of EEN. Twelve of 15 (80%) newly diagnosed CD and seven of 12 (58%) with long-standing disease entered remission. Children with newly diagnosed CD responding to EEN took all feeds orally and gained an average of 4.7+/-3.5 kg with mean PCDAI decreasing from 37.1+/-10.8 to 6.7+/-5.1 after 8 weeks. In addition, four children continued supplementary polymeric formula (without other medical therapies) and all have maintained remission during an average follow-up period of 15.2 months. CONCLUSION: Exclusive enteral feeds induced remission in 80% of children with newly diagnosed CD (on intention-to-treat basis) when used as sole initial therapy while also improving nutritional status. All newly diagnosed children treated with EEN, who were able to establish feeds, achieved remission. In addition, remission may be prolonged with oral supplementary formula as sole ongoing treatment. Further study of the role(s) of enteral feeds and of longer-term benefits of enteral feeding in children with CD is now required.
Abstract: BACKGROUND: To describe the presenting clinical features of coeliac disease in a single paediatric centre, and to determine if the presenting features vary with age. METHODS: A review was conducted of children who had been referred with clinical suspicion of coeliac disease to the paediatric gastroenterology department of a tertiary paediatric hospital in Sydney, Australia. Coeliac disease was defined using standard histological criteria. Medical records were reviewed retrospectively. RESULTS: Clinical data were available for 74 cases of proven coeliac disease. Only 9% of patients were less than 2 years of age at diagnosis. Pre-school children (age < 5 years) presented with different symptoms to school children (age > or = 5 years). The most common presenting features in younger children were diarrhoea, irritability and weight loss. However, in older children, abdominal pain was the most common presenting feature. CONCLUSION: We found a significant difference in the clinical features of coeliac disease in pre-school compared to school age children.
Abstract: Clinical pathways are useful tools in improving the quality of care of patients treated in hospitals. Gastroenteritis is a short, self-limiting, but common illness of childhood associated with significant costs to the community. The authors assessed the impact of a clinical pathway on investigation ordering in children with gastroenteritis. A retrospective analysis of 2 cohorts of children was performed before (n=1498) and after (n=1252) the introduction of a clinical pathway. Children admitted to hospital with a diagnosis of gastroenteritis were assessed as to the type of pathology tests ordered. Further outcomes measured were rates of admission, emergency department presentations, average length of stay, and direct costs. Subset analysis was undertaken on the initial cohort of patients who had a full blood count as part of their initial assessment. Full blood count was more likely to be performed prior to the introduction of the pathway(77.1%) than after pathway introduction (66.8%; P<.004). Urine microscopy and culture also was significantly decreased from 56.3% to 40.4% (P<.0005). Median patient costs were reduced from $1228 to $752 following pathway introduction (P<.0001); however, rates of admission were increased from 18.6% to 28.8% (P<.0001). Length of stay decreased but was not statistically significant. Full blood count results in the subset analysis revealed that the measurement of a full blood count had no impact on management. Thus, a clinical pathway contributed to more rational ordering of pathology tests and lowered the costs to a hospital of caring for patients with this common illness.
Abstract: AIM: To document the concerns and expectations of parents of children with inflammatory bowel disease (IBD) within the context of a multidisciplinary IBD clinic, and to highlight the importance of a holistic approach to the care of these children. METHODS: The parents of 60 children with IBD were surveyed by mailed questionnaire. Parents were asked to provide details of their concerns regarding their child's condition and to express their expectations of medical care. In addition, enquiry was made in respect to the respondents' learning about IBD. RESULTS: Forty-six questionnaires (77%) returned. Fifty-two percent of the patients were male. Patients were aged a mean of 10.9 (+/-4.1) years and diagnosed at an average age of 2.1 (+/-1.8) years previously. The most common concerns expressed by the parents related to the side- effects of medications and the future prospects for their child. Overall, parents were satisfied with aspects of care within the IBD clinic but many suggested additional personnel such as counselors or educators should be available. Parents also reported the need for continuing education and easy access to up-to-date information. CONCLUSION: Parents of children and adolescents with IBD have many common concerns regarding their child's condition. On-going attention to holistic care, including psychosocial and educational elements for patients and families, is appropriate in the context of the chronic and unpredictable nature of IBD.
Abstract: The incidence of reporting and diagnosis of coeliac disease (CD) in children is increasing with the improvement in sensitivity and specificity of screening markers. This in turn has led to an increasing awareness of gluten-sensitive enteropathy and associated disorders. We report the unusual case of an 8-month-old child presenting to his general practitioner with pruritic skin lesions, subsequently proven to be dermatitis herpetiformis (DH) as the first sign of gluten-sensitive disease. This infant is the youngest child presenting with DH who could be identified from published report dating from 1966 onwards. Dermatitis herpetiformis is the commonest associated pathology of CD, although rare in infancy, it should be considered in any child presenting with failure to thrive and atypical, chronic rash not responding to simple measures.
Abstract: INTRODUCTION: Diagnosis of inflammatory bowel disease (IBD) and differentiation between Crohn's disease (CD) and ulcerative colitis (UC) can be difficult in children. Several previous studies suggest that esophagogastroduodenoscopy (EGD) and biopsies are important in the initial investigation of children with suspected IBD. The aim of the present paper was to assess the importance of EGD in the initial diagnostic appraisal of children with suspected IBD. METHODS: Children diagnosed with IBD over a 4-year period were identified from a dedicated IBD database. Retrospective chart review documented presenting signs and symptoms, endoscopic features in the upper and lower gastrointestinal tract and histological findings on mucosal biopsies. RESULTS: Eighty-six children were diagnosed with IBD of whom 61 (70.9%) had CD, 13 (21.3%) UC, and the remainder, indeterminate colitis. Esophagogastroduodenoscopy was performed in 76 (88.4%). Nine children were diagnosed with IBD solely on the basis of information obtained following EGD. None of these children had colitis and all had abnormal histological findings on review of mucosal biopsies from the upper gastrointestinal tract. Thirteen (23.6%) of 55 children with CD had granulomas noted within biopsies obtained during EGD and another 20 had significant inflammatory changes on histological examination of upper gastrointestinal tract biopsies. Crohn's disease was diagnosed in 25 of 38 children with pan-colitis. Thirteen children were correctly classified as having CD only following assessment of their upper gastrointestinal tract. This included the presence of upper gut granulomata in eight children. CONCLUSION: The performance of EGD in these children with IBD provided additional diagnostic yield and guided the differentiation of disease type in many patients. Esophagogastroduodenoscopy is an essential component in the initial diagnostic assessment of children with possible CD or UC.
Abstract: BACKGROUND: Gastric epithelial cell lines have been utilized extensively as tools to define aspects of the interactions between Helicobacter pylori and host epithelial cells. Fetal calf serum (FCS) is employed as a growth stimulant, but it is unclear whether this agent may in itself alter host responses. METHODS: Two gastric epithelial cell lines were utilized to ascertain the effects of varying FCS concentration on cellular responses following H. pylori infection. Media containing 0%, 5% or 10% FCS was added to cell lines prior to infection with H. pylori of defined genotype. Cellular interleukin (IL)-8 production was measured as a marker of cellular response. Effects of altered FCS upon cell viability were also determined by trypan blue exclusion. RESULTS: Interleukin-8 production by AGS cells following H. pylori infection was not altered by variation of media FCS concentration. However, KATO-III cells produced greater amounts of IL-8 when media was FCS-free than at 5% or 10% FCS. Although cellular viability was not altered in AGS cells exposed to varied concentrations of FCS, viability was decreased in serum-free KATO-III cells, but not when cells were kept at 5% FCS. CONCLUSIONS: Serum-derived factors alter cellular responses to H. pylori infection in a cell-line-dependent manner and impaired cellular viability may relate to this effect. However, the mechanisms for these observations are unclear and further work is now required to determine the nature of these important interactions.
Abstract: Orofacial granulomatosis is a term generally used to describe lip swelling secondary to an underlying granulomatous inflammatory process. Granulomatous cheilitis is the histopathological description of such inflammation occurring in the lips and surrounding tissues. Melkersson-Rosenthal syndrome (a triad of orofacial swelling, facial paralysis and a fissured tongue) is one manifestation of orofacial granulomatosis, which more commonly presents as granulomatous cheilitis alone. Oral Crohn's disease also belongs to the entity of orofacial granulomatosis. Most reported cases of orofacial granulomatosis have been in adults and some in adolescents. We present six children presenting with orofacial granulomatosis at an early age (range 5-8 y) whose course points towards the development of Crohn's disease. Conclusion: Orofacial granulomatosis in the paediatric population may be an initial manifestation of Crohn's disease and so careful surveillance is recommended.
Abstract: Vomiting and abdominal symptoms are uncommonly seen in children with Prader-Willi syndrome (PWS). A case is described of a child with PWS who presented with vomiting, abdominal distension and abdominal pain due to a duodenal web causing gross gastric distension. Prompt attention to the onset of such clinical features in children with PWS may prevent excess morbidity and complications.
Abstract: OBJECTIVE: Although there are published guidelines representing the consensus of several large groups, it is unclear whether these are used by practitioners in the management of Helicobacter pylori infection in children and if the guidelines are relevant to particular regions of the world. The aim of this study was to answer these questions in regard to the Australasian region. METHODS: An email-based questionnaire was circulated to Australasian paediatric gastroenterologists to ascertain aspects of practice related to H. pylori infection in children and to review practitioner awareness and use of the guidelines. RESULTS: Twenty-five (78%) of 32 questionnaires were completed. Current practice reported by the respondents followed the principles of the published guidelines. However, only 15 gastroenterologists were aware of the guidelines: a number of these practitioners were uncomfortable adapting the published guidelines to their local situation. CONCLUSIONS: Although widely distributed in the paediatric gastroenterology literature, guidelines for management of H. pylori infection may not be utilized fully by individual practitioners. As these guidelines are updated, based upon current developments in the understanding of H. pylori disease, attempts should be made to ensure that such documents are widely distributed to practitioners and that they reflect regional variations in disease patterns.
Abstract: Helicobacter pylori colonization of the stomach results in a chronic-active gastritis characterized by mucosal infiltration of both neutrophils and lymphocytes. A T helper lymphocyte (Th1) profile predominates, which promotes the chronic and persistent inflammatory changes in the gastric mucosa in response to this bacterial pathogen. The cytokine interleukin-18 induces production of interferon-gamma by activated T lymphocytes and promotes a Th1 profile. An in vitro model system was utilized to determine the role of interleukin-18 in response to infection of gastric epithelial cells by H. pylori. H. pylori isolates, characterized with respect to cagE and cagA and VacA status, were employed to infect AGS gastric epithelial cells. Interleukin-18 production was determined by immunoassay. Infection of AGS cells with H. pylori resulted in a 1.8-fold increase in interleukin-18 compared to uninfected cells (22.7+/-2.4 vs. 12.7+/-2.2 pg/ml; P < 0.005). This interleukin-18 response was independent of the cagE status of infecting strains (23.3+/-1.9 vs. 26.3+/-3.6 pg/ml; P = NS). Exposure of AGS cells to recombinant interleukin-18 resulted in dose-dependent and time-dependent secretion of interleukin-8 that was maximal following exposure to 100 pg/ml interleukin-18 for 24 hr (292+/-5 pg/ml, versus 102+/-14 pg/ml in unstimulated cells; P < 0.001). Interleukin-8 secretion was inhibited following pretreatment of cells with anti-interleukin-18 antibody and by pharmacological inhibition of the nuclear transcription factor, NF-kappaB. These findings demonstrate that interleukin-18 can enhance host chemokine response to H. pylori infection.
Abstract: BACKGROUND AND AIMS: Helicobacter pylori infection of the stomach is commonly associated with infiltration of neutrophils. Gastric epithelial cells are recognized as central mediators of tissue responses to this organism. The aim of the present study was to ascertain patterns of production of three neutrophil chemoattractant chemokines following infection of gastric epithelial cells with H. pylori in vitro. METHODS: Two gastric cancer-derived epithelial cell lines were infected with H. pylori organisms of previously defined cagE and cagA status for periods of up to 24 h. The production of three chemokines (interleukin [IL]-8, epithelial neutrophil activating protein [ENA]-78 and growth-related oncogene [GRO]-alpha) over this time was measured in culture supernatants using immunoassays. RESULTS: Both IL-8 and GRO-alpha were produced by both AGS and KATO-III cells in response to H. pylori infection, and in a cag PAI-dependent manner. ENA-78, however, was not increased following H. pylori infection. CONCLUSIONS: GRO-alpha is expressed by epithelial cells following H. pylori infection along with IL-8. Both may contribute to neutrophilic infiltration present in gastric mucosa associated with H. pylori infection. In contrast, H. pylori infection does not lead to an increased synthesis of ENA-78, suggesting that this may not be as important in vivo.
Abstract: OBJECTIVES: The use of complementary and alternative medicines (CAM) appears increasingly prevalent in children and adolescents. Individuals with chronic illness may have patterns of greater usage. This questionnaire-based study aimed to ascertain the frequency of use by a group of children with proven inflammatory bowel disease (IBD) and to consider the reasons for their use. METHODS: A questionnaire was sent by mail to the parents of patients currently attending a paediatric IBD clinic. Parents were asked to describe their child's usage of alternative and probiotic therapies and to comment on a number of aspects of such therapies. RESULTS: Forty-six (77%) of 60 mailed questionnaires were returned. The mean age of the children was 10.9 (+/- 4.1) years and they were taking an average of 1.7 (+/- 0.8) prescribed medications. Thirty-three (72%) of the children were said by their parents to be having CAM, with four having five or more such therapies (average 2.4 +/- 1.3 agents per child). The most commonly used agents were probiotics (78%) and fish oils (56%). A minority (12%) of respondents reported that their child's CAM was very effective, although many (50%) noted partial benefits. The 13 children who had never used any CAM therapies ('non-users') did not differ from the 'users' in terms of gender, age, disease or duration of disease. As expected, non-users expressed greater concerns about use of CAM and described different attitudes towards such therapies. CONCLUSION: Complementary and alternative medicines, especially probiotic therapies, frequently are administered to children and adolescents with inflammatory bowel disease. Often this appears to be due to parental frustration with managing their child's chronic illness. Practitioners caring for children and adolescents with IBD need to be aware that their patients may be using alternative therapies and adopt an open attitude in this situation.
Abstract: Intestinal lymphangiectasia is a well-recognized complication of the Fontan procedure, occurring in up to 24% of patients. Because of the loss of chylous fluid into the gut lumen, protein-losing enteropathy results as well as lymphopenia and hypogammaglobulinaemia. In some cases, dilated lymphatics in the intestinal serosa or mesentery also rupture, causing chylous ascites. Standard medical and cardiac surgical interventions are generally ineffective and the condition is frequently lethal. We report a case of intractable and life-threatening chylous ascites and chylothorax in a 14-year-old girl, associated with intestinal lymphangiectasia and protein-losing enteropathy after a Fontan procedure for tricuspid atresia. The condition was refractory to all standard medical therapies, including dietary modifications, diuretics, corticosteroid therapy, albumin infusions, octreotide, heparin, bowel rest, and parenteral nutrition. Cardiac surgery to optimize her hemodynamic status was also ineffective and large volume pleural and ascitic fluid losses continued. Having exhausted all other therapeutic modalities, (99m)technetium-dextran scintigraphy was performed to assess the extent of intestinal protein loss and the potential for surgical intervention. Scintigraphy suggested localized protein loss from the proximal jejunum and subsequent segmental resection was effective. Postoperatively, ascites and pleural effusions resolved, and there was no evidence of short bowel syndrome. Growth has accelerated and the patient has entered puberty. There is mild persistent intestinal protein loss requiring diuretic therapy. Ascites or pleural effusions are absent, and the patient remains well >2 years after surgery. Intestinal lymphangiectasia post-Fontan procedures has traditionally been ascribed to hemodynamic factors such as raised systemic venous pressure, which would predispose to a generalized intestinal lesion. However, in this case, scintigraphy demonstrated a localized, surgically correctible lesion. To our knowledge, this is the first reported case of the use of (99m)technetium-dextran scintigraphy for this indication and of successful partial small bowel resection in such a case.
Abstract: BACKGROUND: An accurate diagnosis of Helicobacter pylori infection in children currently relies upon histological assessment or culture of gastric biopsies obtained at endoscopy. Noninvasive testing would permit simpler assessment of children with dyspeptic symptoms. The primary aim of the present study was to prospectively evaluate a novel urea breath testing method in children undergoing diagnostic assessment of dyspeptic symptoms and secondarily to consider the roles of other noninvasive tests in these children. METHODS: Laser associated ratio analysis (LARA)-13C urea breath testing was performed on children presenting with upper gastrointestinal symptoms for diagnostic endoscopy. Serum and stool were collected for performance of serology and stool antigen testing, respectively. Histology and culture of endoscopic biopsies of the gastric antrum were used to establish H pylori infection status. RESULTS: Eight (36%) of 22 children were H pylori-positive by histology or culture of gastric biopsies. Urea breath testing showed a sensitivity of 75%, but specificity of 100%. The deletion of a test meal from the urea breath test protocol in eight patients did not alter the utility of the test. Serology provided sensitivity of 87.5%, but a specificity of only 75%. Stool antigen testing in eight available samples provided sensitivity of 50% and specificity of 100%. CONCLUSIONS: The LARA-urea breath testing method provided less sensitivity in this group of children than suggested from previous studies. However, urea breath testing in children is easy to complete and provides rapid noninvasive results. Breath testing protocols require standardization; for instance, the addition of a test meal may not be necessary in older children. Although noninvasive tests for the presence of H pylori in children may provide accurate results and can be considered for use in the initial assessment of dyspeptic children, further work is required to establish the most accurate testing methods.
Abstract: Recent evidence suggests that immune-mediated gastric epithelial cell apoptosis through Fas-Fas ligand interactions participates in Helicobacter pylori disease pathogenesis. To define the role of Fas signaling in vivo, H. pylori strain SS1 infection in C57BL/6 mice was compared to that in mice deficient in the Fas ligand (gld). gld mice had a degree of gastritis similar to that of C57BL/6 mice after 6 weeks (gastritis score, 5.2 +/- 0.6 [mean +/- standard error] versus 3.5 +/- 0.8) and 12 weeks (4.0 +/- 0.7 versus 3.4 +/- 0.5) of infection. Bacterial colonization was comparable in each group of mice at 12 weeks of infection (2.1 +/- 0.3 versus 1.6 +/- 0.3 for gld and C57BL/6, respectively; the difference is not significant). Sixty-seven percent of H. pylori-infected gld mice displayed atrophic changes in the gastric mucosa, compared with 37% of infected C57BL/6 mice, at 12 weeks. In addition, atrophic changes were more severe in H. pylori-infected gld mice (P < 0.05). Splenocytes isolated from H. pylori-infected C57BL/6 mice had a twofold increase in production of the Th1 cytokine gamma interferon (IFN-gamma) in response to H. pylori antigens at both 6 and 12 weeks compared to controls (143 +/- 65 versus 69 +/-26 pg/ml and 336 +/- 73 versus 172 +/- 60, respectively). In contrast, there was a lack of detectable IFN-gamma in gld mice infected with the bacterium. H. pylori-infected C57BL/6 mice had increased epithelial cell apoptosis compared with sham-infected C57BL/6 mice (35.0 +/- 8.9 versus 12.3 +/- 6.9; P < 0.05). Epithelial cell apoptosis did not differ between H. pylori-infected and control gld mice (5.2 +/- 1.6 versus 6.5 +/- 2.9 [not significant]). These data demonstrate that mice with mutations in the Fas ligand develop more severe premalignant mucosal changes in response to infection with H. pylori in association with both an impaired gastric epithelial cell apoptotic response and IFN-gamma production. The Fas death pathway modulates disease pathophysiology following murine infection with H. pylori. Deregulation of the Fas pathway could be involved in the transition from gastritis to gastric cancers during H. pylori infection.
Abstract: OBJECTIVES: Complementary and alternative medicines (CAM) and probiotic therapies appear to be increasingly accepted and used. This questionnaire-based study aimed to ascertain the frequency of use and the acceptance of these therapies by children attending outpatient gastroenterology clinics. METHODS: Parents accompanying children to their appointments were asked to complete a questionnaire in order to determine usage of probiotic and alternative therapies. Questions also ascertained relevant background information and parental acceptance of alternative therapies. RESULTS: Ninety-two questionnaires were completed. The ages of the children varied from 6 months to 16 years (mean +/- SD; 6.5 +/- 4.3 years) and they had been prescribed an average of 1.7 +/- 1.3 (range 0-6) conventional medications. Thirty-three children (35.9%) were taking CAM and 98.6% of parents answered that they would be prepared to administer CAM to their child. Symptomatic improvements were attributed to CAM by the parents of 24 out of 33 children given these therapies. In addition, probiotic therapies were utilized by 23.8% of children, and 93.0% of parents would administer probiotic agents if recommended for their child's condition. CONCLUSION: Complementary and alternative medicines and probiotic therapies are used frequently by children attending gastroenterology clinics and are accepted widely by their parents.
Abstract: BACKGROUND: Rapid non-invasive diagnostic tests that can reliably document the presence or absence of Helicobacter pylori infection are urgently required. The aim of this study was to determine the accuracy of two immunoassays (Flex-Sure and MedMira), developed for use outside the laboratory setting by practitioners, in the setting of a low prevalence of H. pylori infection. METHODS: Serum samples collected in four previous studies (n = 349) were employed to detect the presence of H. pylori-specific immunoglobulin G, compared to previous results obtained using endoscopic biopsies, serology, flow cytometry, and urease breath testing. Serum samples included 52 obtained from adults (parents and grandparents of symptomatic children), 123 sera collected from children and adolescents undergoing diagnostic upper endoscopy for upper gastrointestinal tract symptoms, and 174 samples drawn from children in the primary care setting with or without recurrent abdominal pain. RESULTS: Overall, 16% of subjects were infected by the gastric pathogen. Both the specificity (%) and negative predictive value (%) of the two tests were high (FlexSure: 91 and 92; Medmira: 97 and 94, respectively). In adults, both tests also demonstrated high sensitivity (83% and 86%) and positive predictive values (79% and 83%, respectively). However, in children where the prevalence of infection was 12% (37 of 297 subjects), the sensitivity (59% and 71%) and positive predictive values (55% and 88%, respectively) of the immunoassays were lower. CONCLUSIONS: These findings indicate that, in the setting of a low prevalence of H. pylori infection, the MedMira office-based test provides satisfactory results and utility. However, the low positive-predictive value of the FlexSure kit may limit applicability of this test in children.
Abstract: OBJECTIVES: Aspiration of gastric contents is a relatively common cause of acute and chronic pulmonary disease. However, a reliable method of diagnosing recurrent aspiration is currently lacking. The aim of this study was to determine whether the presence of gastric pepsin in tracheal aspirates of infants and children might be used as a reliable marker of the microaspiration of refluxed gastric contents. METHODS: Ninety-eight children undergoing general anesthesia and tracheal intubation participated in the study. Sixty-four of 98 children underwent endoscopy for clinically significant gastroesophageal reflux. Thirty-four children from routine operative lists were nonreflux controls. These two groups were further subdivided based on the presence or absence of associated respiratory symptoms. After endotracheal intubation, tracheal aspirates were obtained and subsequently assayed for gastric pepsin using a fluoroscein isothiocyanate casein. RESULTS: Pepsin was detected in 7 of 27 children with reflux symptoms alone and in 7 of 8 of those with chronic respiratory symptoms. In addition, pepsin was present in 31 of 37 children with a history of both reflux and chronic respiratory symptoms. Tracheal pepsin was not detected in any of the 26 children without gastroesophageal reflux or respiratory symptoms. Tracheal pepsin was found significantly more frequently in children with reflux symptoms than in those without, particularly in children with both reflux and respiratory problems. CONCLUSION: Tracheal pepsin assay as a reliable marker of gastroesophageal reflux aspiration.
Abstract: OBJECTIVES: Refluxed gastric material aspirated into the lungs is an important cause of acute and chronic pulmonary disease. Currently, the presence of fat-laden macrophages (FLM) in tracheobronchial secretions of children is a conventional marker for reflux aspiration. However, this assay is limited by its apparent lack of specificity. The aim of this study was to reevaluate the role of this assay in diagnosing reflux aspiration. METHODS: The tracheal aspirates of sixty-four consecutive children with clinically significant gastroesophageal reflux undergoing upper gastrointestinal endoscopy under general anesthesia, and 34 other children from the routine operative schedule were evaluated. Both groups were further subdivided on the basis of presence or absence of associated respiratory symptoms. After intubation, tracheal aspirates were collected, fixed, and stained for FLM. By grading the amount of intracellular fat present, a semiquantitative lipid index was computed. Tracheal aspirates with a lipid index of 100 or greater were considered positive. RESULTS: Twenty-four of the 64 children with reflux symptoms and 14 of 34 children without reflux symptoms were positive for FLM. Sixteen of 37 children with both gastroesophageal reflux and respiratory symptoms and 10 of 26 children negative for both tested positive for FLM. The mean lipid index of the subgroup of children with both reflux and respiratory symptoms was not significantly different from that of the subgroup that was negative for both conditions. Despite computing a semiquantitative lipid index, an index of 100 or greater only had a sensitivity of 38% and specificity of 59%. CONCLUSION: Assay of FLM in the tracheal aspirates of children considered at risk of reflux aspiration is not a sensitive or specific as a marker for reflux aspiration.
Abstract: AIMS: To evaluate the short and long term morbidity of gastrostomy insertion, and to identify ongoing management requirements. METHODS: A retrospective review was undertaken of the hospital casenotes of children aged up to fifteen years who had a gastrostomy placed in Christchurch over a six year period to March 1998. RESULTS: 42 children had a gastrostomy fashioned, 35 in the last three years of the period reviewed. The most common underlying diagnosis was neurological disease (48%), and the most common indication for tube placement was failure to feed orally. Complications were frequent but minor. Morbidity was related to local erythema and infection around the stoma (85 episodes in 23 children), persistent and major gastric fluid leakage (three episodes), and mechanical failure of the tube (21 episodes). Gastro-oesophageal reflux was seen in fourteen children, nine of whom had primary neurological disease. Complications were seen more after open gastrostomy than after percutaneous endoscopic placement (6.6:4.7). There was no mortality related directly to the gastrostomy tube or tube placement. CONCLUSIONS: An increase in the frequency of gastrostomy placements has been seen over this period. As the number of children with a gastrostomy increases, so too have the demands on medical and nursing staff to care for and manage the devices. The frequency of minor ongoing problems necessitates ongoing support of the child and care of the gastrostomy. A close working relationship between outreach nursing staff, stoma therapists and medical staff is required if morbidity is to be minimised. Education, audit and review remain important additional aspects of care.
Abstract: Gastric infection with Helicobacter pylori results in chronic active gastritis and in some individuals is associated with complications such as peptic ulceration and gastric cancers. A balance between bacterial factors and host responses may determine disease outcome. The mouse-adapted H. pylori strain SS1 has been utilized as a model to study disease pathogenesis. Although chronic gastritis is observed in this murine model of H. pylori infection, other complications of disease seen in the human host (such as peptic ulceration) are not identified. The objectives of this study were to characterize virulence factors of the mouse-adapted H. pylori strain SS1 and determine host responses to infection. Vacuolating cytotoxin activity of H. pylori strain SS1 was determined after incubation of HEp-2 cells with culture supernatant for 24 hr. Polymerase chain reaction was performed to detect the presence of the cagA and cagE genes. Chemokine responses from human gastric epithelial cells infected with H. pylori SS1 were assessed by measurement of the concentration of interleukin-8 in cell-free supernatants. C57BL/6 and gld mice were infected with strain SS1 or sham-infected. Eight weeks following infection, gastric tissues were obtained for histological analysis and surface hydrophobicity was measured by axisymmetric drop-shape analysis. H. pylori strain SS1 was cytotoxin negative, cagA positive, and cagE positive, but induced only a modest interleukin-8 response (684 +/- 140 pg/ml) from AGS gastric epithelial cells in comparison to a clinical isolate (4170 +/- 410 pg/ml, P < 0.0005). Increased inflammation was observed in the stomachs of H. pylori strain SS1-infected animals compared to uninfected controls. Gastritis was not associated with any disease complications. Despite mucosal inflammation, infected mice did not demonstrate alterations in gastric surface hydrophobicity (42.2 degrees +/- 2.2 degrees and 41.4 degrees +/- 3.2 degrees for C57BL/6 and gld, respectively) compared to uninfected mice (43.2 degrees +/- 2.3 degrees and 39.5 degrees +/- 1.6 degrees, respectively). In conclusion, murine infection with H. pylori SS1, which contains putative bacterial virulence factors, results in gastric inflammation. However, the mucosal changes are not associated with alterations in surface hydrophobicity. Therefore, the mouse model of infection with H. pylori, strain SS1 may not serve as an entirely appropriate model to study host factors associated with disease complications.
Abstract: This study was undertaken to determine whether infection with Helicobacter pylori strains that contain the cagE gene was associated with duodenal ulceration in children. The presence of flaA, cagA, and cagE genes was determined by polymerase chain reaction in H. pylori previously cultured from 29 children. Twelve (92%) of 13 children with duodenal ulcers were infected with cagE-positive isolates, compared with only 5 (31%) of 16 with gastritis alone (P<.01). Infection of gastric cells in tissue culture by cagE-positive H. pylori resulted in greater increments in interleukin-8 levels compared with cagE-negative strains (2.3+/-0.1 vs. 1.3+/-0.2 ng/mL in AGS cells [P<.005]; 1.5+/-0.3 vs. 0.5+/-0.2 ng/mL in KATO-III cells [P<.05]). H. pylori-containing cagE was associated with the presence of duodenal ulceration in children. Enhanced chemokine production after infection with cagE-positive H. pylori could affect disease outcome.
Abstract: AIMS: To determine the prevalence of coeliac disease in selected groups of children presenting to a paediatric department. METHODS: Children presenting to the Paediatric Department at Christchurch Hospital were enrolled upon identification of one or more factors associated with increased risk of coeliac disease. All subjects were screened with anti-endomysial antibody and antigliadin antibody tests. Those children with positive tests underwent small bowel biopsy. RESULTS: 36 of 153 children had abnormal antibody tests. Seven (4.5%) of 34 children who underwent small bowel biopsies were found to have histological findings consistent with coeliac disease. Five of these children had presented with symptoms not classically ascribed to coeliac disease (failure to gain weight or non-specific abdominal pain). CONCLUSIONS: The possibility of coeliac disease should be considered in children with atypical symptoms and the diagnosis excluded by appropriate testing. Recognition of the variable presentations associated with coeliac disease in children is clinically relevant.
Abstract: OBJECTIVE: To evaluate the efficacy of oral tacrolimus as an induction agent in steroid-refractory severe colitis. STUDY DESIGN: Open-label, multicenter trial of oral tacrolimus in patients with severe colitis. Patients not responding to conventional therapy received tacrolimus, 0.1 mg/kg/dose given twice a day, and the dosage was adjusted to achieve blood levels between 10 and 15 ng/mL. Response was defined as improvement in a number of clinical parameters (including abdominal pain, diarrhea, rectal bleeding, and cessation of transfusions). Patients who responded by 14 days continued to receive tacrolimus, and 6-mercaptopurine or azathioprine was added as a steroid-sparing agent 4 to 6 weeks after the tacrolimus was instituted. RESULTS: Fourteen patients were enrolled in the study. One patient elected to withdraw after 48 hours. Of the 13 remaining, 9 (69%) responded and were discharged. Tacrolimus was continued for 2 to 3 months in the responders, except for 1 patient who was given tacrolimus for 11 months. After 1 year of follow-up, only 5 (38%) patients were receiving maintenance therapy; the other 4 responders had undergone colectomy. CONCLUSION: Although tacrolimus is effective induction therapy for severe ulcerative or Crohn's colitis, fewer than 50% of patients treated will successfully achieve a long-term remission.
Abstract: Coeliac disease and inflammatory bowel disease (IBD) individually are not uncommon in children, but the occurrence of both conditions together is rare. The combined presentation of coeliac disease and IBD in a girl of 7 years is presented with a review of the related literature. The occurrence of coeliac disease with IBD should be considered at the time of diagnosis and at relapse, or where there is difficulty maintaining remission in established IBD. Screening with serum antibody tests may be helpful.
Abstract: Helicobacter pylori causes chronic active (type B) gastritis in the overwhelming majority of infected individuals. The relative contribution of virulence factors in the bacterium and host responses to the microbial infection in determining which subjects will go on to develop complications - such as peptic ulceration, gastric cancers and gastric lymphomas - is the subject of current investigative activities.
Abstract: Short bowel syndrome can present many complex management issues and may be complicated by various metabolic problems. D-lactic acidosis in the setting of short bowel syndrome has been described only rarely in children. A further case is presented with a review of typical clinical manifestations of D-lactic acidosis and reported management options. Early recognition and appropriate management is essential to avoid morbidity secondary to this complication of short bowel syndrome. Probiotic therapies may have an increasing role in prevention and management of this complication.
Abstract: The mechanisms involved in mediating the enhanced gastric epithelial cell apoptosis observed during infection with Helicobacter pylori in vivo are unknown. To determine whether H. pylori directly induces apoptosis of gastric epithelial cells in vitro and to define the role of the Fas-Fas ligand signal transduction cascade, human gastric epithelial cells were infected with H. pylori for up to 72 h under microaerophilic conditions. As assessed by both transmission electron microscopy and fluorescence microscopy, incubation with a cagA-positive, cagE-positive, VacA-positive clinical H. pylori isolate stimulated an increase in apoptosis compared to the apoptosis of untreated AGS cells (16.0% +/- 2.8% versus 5.9% +/- 1. 4%, P < 0.05) after 72 h. In contrast, apoptosis was not detected following infection with cagA-negative, cagE-negative, VacA-negative clinical isolates or a Campylobacter jejuni strain. In addition to stimulating apoptosis, infection with H. pylori enhanced Fas receptor expression in AGS cells to a degree comparable to that of treatment with a positive control, gamma interferon (12.5 ng/ml) (148% +/- 24% and 167% +/- 24% of control, respectively). The enhanced Fas receptor expression was associated with increased sensitivity to Fas-mediated cell death. Ligation of the Fas receptor with an agonistic monoclonal antibody resulted in an increase in apoptosis compared to the apoptosis of cells infected with the bacterium alone (38.5% +/- 7.1% versus 16.0% +/- 2.8%, P < 0.05). Incubation with neutralizing anti-Fas antibody did not prevent apoptosis of H. pylori-infected cells. Taken together, these findings demonstrate that the gastric pathogen H. pylori stimulates apoptosis of gastric epithelial cells in vitro in association with the enhanced expression of the Fas receptor. These data indicate a role for Fas-mediated signaling in the programmed cell death that occurs in response to H. pylori infection.
Abstract: Helicobacter pylori infection is primarily acquired during childhood, causes chronic, active gastritis and peptic ulcer disease, and is associated with the development of gastric malignancies. However, only a small number of infected individuals ever develop the more severe sequelae of peptic ulcer disease and gastric cancers. Therefore, the identification of bacterial and host factors that play a role in determining the outcomes and pathophysiology of infection is a major focus of current research. Recent advances in the understanding of disease pathogenesis are critically considered, with particular reference to the pediatric population.
