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Biomedical subjects

Andrew S Day

Publications and source records attributed to Andrew S Day.

At least 19 recordsLinked to original sources
PubMed2006

Fecal S100A12: a novel noninvasive marker in children with Crohn's disease.

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.

Adolescent↗
PubMed2006

Exclusive enteral feeding as primary therapy for Crohn's disease in Australian children and adolescents: a feasible and effective approach.

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.

Adolescent↗
PubMed2005

Age related clinical features of childhood coeliac disease in Australia.

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.

Abdominal Pain↗
PubMed2005

Role of serum factors in epithelial cell responses to Helicobacter pylori infection in vitro.

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.

Animals↗
PubMed2005

Role of esophagogastroduodenoscopy in the initial assessment of children with inflammatory bowel disease.

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.

Adolescent↗
PubMed2004

Gastric epithelial cell CXC chemokine secretion following Helicobacter pylori infection in vitro.

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.

Analysis of Variance↗
PubMed2003

Use of LARA-urea breath test in the diagnosis of Helicobacter pylori infection in children and adolescents: a preliminary study.

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.

Adolescent↗
PubMed2003

Successful resection of localized intestinal lymphangiectasia post-Fontan: role of (99m)technetium-dextran scintigraphy.

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.

Adolescent↗
PubMed2002

Accuracy of office-based immunoassays for the diagnosis of Helicobacter pylori infection in children.

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.

Adolescent↗
PubMed2002

Assay of tracheal pepsin as a marker of reflux aspiration.

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.

Biomarkers↗
PubMed2002

Fat laden macrophages in tracheal aspirates as a marker of reflux aspiration: a negative report.

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.

Biomarkers↗
PubMed2002

Enhanced disease severity in Helicobacter pylori-infected mice deficient in Fas signaling.

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.

Animals↗
PubMedDate not supplied

Helicobacter pylori infection induces interleukin-18 production in gastric epithelial (AGS) cells.

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.

Cell Line↗
PubMedDate not supplied

Coeliac disease presenting as dermatitis herpetiformis in infancy.

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.

Celiac Disease↗
PubMedDate not supplied

A case of duodenal web occurring in Prader-Willi syndrome.

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.

Abdominal Pain↗