Anthony G. Catto-Smith

High incidence of inflammatory bowel disease in Australia: A prospective population-based Australian incidence study

Background: To date, there have been no population‐based epidemiological studies published from Australia concerning the incidence of inflammatory bowel disease (IBD). Our hypothesis was that the incidence of IBD in Australia is at least as high as other industrialized countries, given similar genetic and environmental risk factors. Methods: A prospective, population‐based IBD incidence study was conducted between April 2007 and March 2008 in Greater Geelong, Victoria, Australia. According to 2006 Australian Census data, this comprises an at‐risk population of 259,015. Cases were ascertained from multiple overlapping sources. All local general practitioners, gastroenterologists, surgeons, and pediatricians were contacted every 2 months to identify new IBD cases. The Royal Childrens Hospital in Melbourne, local endoscopy and pathology centers were also searched to ensure completeness of case capture. Standard IBD case definitions were used with clinical, endoscopic, and histological criteria. Results: In all, 76 new cases of IBD were identified during the 1‐year period. There were 45 cases of Crohns disease, 29 of ulcerative colitis, and 2 of indeterminate colitis. The crude annual incidence rates for IBD overall, Crohns disease, ulcerative colitis, and indeterminate colitis were 29.3 per 100,000 (95% confidence interval [CI] 23.5–36.7 per 100,000), 17.4 per 100,000, 11.2 per 100,000, and 0.8 per 100,000, respectively. When directly age‐standardized to the World Health Organization standard population the overall IBD incidence rate was 29.6 per 100,000. Conclusions: This is the first prospective, Australian population‐based IBD incidence study. The incidence rates are among the highest reported in the literature of IBD. (Inflamm Bowel Dis 2009)

Increasing incidence of Crohn's disease in Victorian children

Background: The incidence of Crohns disease has been increasing in Western communities, but there are no published studies which have examined this change in children in Australia. The centralization of pediatric gastroenterology services in Victoria provides an opportunity to examine these changes within one state.

Postural drainage and gastro-oesophageal reflux in infants with cystic fibrosis

Gastro-oesophageal reflux is increased in cystic fibrosis and it is possible that postural drainage techniques may exacerbate reflux, potentially resulting in aspiration and further impairment of pulmonary function. AIM To evaluate the effects of physiotherapy with head down tilt (standard physiotherapy, SPT) on gastro-oesophageal reflux and to compare this with physiotherapy without head down tilt (modified physiotherapy, MPT). METHOD Twenty (mean age 2.1 months) infants with cystic fibrosis underwent 30 hour oesophageal pH monitoring during which SPT and MPT were carried out for two sessions each on consecutive days. RESULTS The number of reflux episodes per hour, but not their duration, was significantly increased during SPT compared with MPT (SPT 2.5 (0.4) v MPT 1.6 (0.3), p = 0.007) and to background (1.1 (0.)1, p = 0.0005). Fractional reflux time was also increased during SPT (11.7 (2.6)%) compared with background (6.9 (1.3)%, p = 0.03) but not compared with MPT (10.7 (2.7)%). There was no significant difference between MPT and background for number of reflux episodes, their duration, or fractional reflux time. CONCLUSION SPT, but not MPT, was associated with a significant increase in gastro-oesophageal reflux in infants with cystic fibrosis.

Mycobacterium avium subspecies paratuberculosis in children with early-onset Crohn's disease.

Background: Mycobacterium avium subspecies paratuberculosis (MAP) is the most enduring infectious candidate that may be associated with inflammatory bowel disease (IBD). It is possible that the inconsistencies in the prevalence studies of MAP in adults reflect clinical differences in adult patients studied, including duration of disease and treatment regimens, and also in lack of specificity of some of the assays used. The aim was to determine the presence of MAP in children with symptoms of Crohns disease (CD) and ulcerative colitis (UC), using gut biopsy tissue and peripheral blood mononuclear cells (PBMC) collected at initial endoscopic examination prior to clinical treatment. Methods: Mucosal biopsies and/or PBMC specimens were collected from a total of 142 children, comprising 62 with CD, 26 with UC, and 54 with non‐IBD. MAP‐specific IS900 polymerase chain reaction (PCR) analysis was performed on all biopsies and PBMC specimens. Conventional MAP culture technique was performed on a subset of 10 CD, 2 UC, and 4 non‐IBD patients to isolate MAP. Results: MAP was identified by IS900 PCR significantly more often in mucosal biopsies from CD 39% (22/56) than from non‐IBD 15% (6/39) patients (P < 0.05), and in PBMC from CD 16% (8/50) than from non‐IBD 0% (0/31) patients (P < 0.05). Viable MAP were cultured from mucosal biopsies from 4/10 CD, 0/2 UC, and 0/4 non‐IBD patients, but were not cultured from PBMC specimens. Conclusions: This unique study on the occurrence of MAP in gut tissue and blood from pediatric IBD patients suggests the possible involvement of MAP in the early stages of development of CD in children. Inflamm Bowel Dis 2009

Effect of gluten-free diet and adherence on growth and diabetic control in diabetics with coeliac disease.

Aims: To study the effect of gluten-free diet on growth and diabetic control of children with type 1 diabetes mellitus and coeliac disease. Methods: Twenty one children (mean age 7.5 years, range 1.6–12.9) with type 1 diabetes, primarily initially identified on the basis of symptoms and consecutively diagnosed with coeliac disease by biopsy over a 10 year period, were matched by sex, age at onset, and duration of diabetes with two diabetic controls without coeliac disease. Weight, height, haemoglobin A1c, and insulin requirements were measured before and for 12 months after the diagnosis and treatment of coeliac disease. Dietary awareness and adherence were assessed by structured questionnaire. Results: A gluten-free diet resulted in a significant increase in weight-for-age z scores at 12 months after diagnosis (mean increase in z score 0.33) and in BMI (mean increase in z score 0.32). Increases in height did not achieve statistical significance. Controls showed no significant changes in weight, height, or BMI over the same period. Insulin dosage at diagnosis was less in coeliacs than in controls (mean difference 0.16 units/kg/day), but was similar to controls once a gluten-free diet had been established. Questionnaires were obtained in 20 patients. There appeared to be a relation between dietary awareness/adherence and growth parameters, but the small number of patients with “poor/fair” dietary adherence prevented meaningful analysis of this group. Conclusion: Identification and dietary treatment of coeliac disease in children with diabetes improved growth and influenced diabetic control. Evaluation of the outcome of treatment of coeliac disease in diabetics should include assessments of gluten intake.

Esophageal eosinophilia in children with dysphagia.

Objectives Children occasionally have dysphagia in the absence of an apparent primary cause. Esophageal eosinophilia is sometimes seen in these patients at the time of upper endoscopy but its significance is not clear. Although eosinophilia is regarded by some as a histologic hallmark of childhood reflux esophagitis, it may in fact signal a primary eosinophilic esophagitis in children with dysphagia. Our aim was to evaluate esophagitis, acid reflux determined by pH probe, and esophageal eosinophilia in children with the primary complaint of dysphagia. Methods A retrospective study was performed in 42 children, admitted for investigation of dysphagia, in whom no primary cause could be found. Twenty-one children (mean age ± SD, 10.1 ± 4.0 years) had esophageal eosinophilia and 21 children (8.3 ± 4.7 years) did not. Clinical, endoscopic, manometric and esophageal pH parameters in these two groups were compared. Results Patients with esophageal eosinophilia were more often male (p<0.01) with a history of allergy (p<0.001) and food bolus obstruction (p<0.05) requiring endoscopic removal. Their esophageal mucosa appeared wrinkled and thickened at endoscopy with basal cell proliferation, and large numbers of eosinophils in esophageal mucosal biopsies. Continuous esophageal pH records and motility studies, when obtained, were similar in both groups and were within normal values. Conclusion Children with dysphagia who have esophageal eosinophilia are unlikely to have pathologic gastroesophageal reflux.

Fecal incontinence after the surgical treatment of Hirschsprung disease

We examined 60 children 8.9 years (+/- 2.6 years) after surgical treatment of Hirschsprung disease to determine the extent of fecal incontinence. Thirty-two children (53%) had significant fecal soiling and 16 (27%) less severe soiling. The prevalence of incontinence did not diminish with increasing age.

Decreased colonic transit time after transcutaneous interferential electrical stimulation in children with slow transit constipation

PURPOSE Idiopathic slow transit constipation (STC) describes a clinical syndrome characterised by intractable constipation. It is diagnosed by demonstrating delayed colonic transit on nuclear transit studies (NTS). A possible new treatment is interferential therapy (IFT), which is a form of electrical stimulation that involves the transcutaneous application of electrical current. This study aimed to ascertain the effect of IFT on colonic transit time. METHODS Children with STC diagnosed by NTS were randomised to receive either 12 real or placebo IFT sessions for a 4-week period. After a 2-month break, they all received 12 real IFT sessions-again for a 4-week period. A NTS was repeated 6 to 8 weeks after cessation of each treatment period where able. Geometric centres (GCs) of activity were calculated for all studies at 6, 24, 30, and 48 hours. Pretreatment and posttreatment GCs were compared by statistical parametric analysis (paired t test). RESULTS Thirty-one pretreatment, 22 postreal IFT, and 8 postplacebo IFT studies were identified in 26 children (mean age, 12.7 years; 16 male). Colonic transit was significantly faster in children given real treatment when compared to their pretreatment NTS at 24 (mean CG, 2.39 vs 3.04; P < or = .0001), 30 (mean GC, 2.79 vs 3.47; P = .0039), and 48 (mean GC, 3.34 vs 4.32; P = .0001) hours. By contrast, those children who received placebo IFT had no significant change in colonic transit. CONCLUSIONS Transcutaneous electrical stimulation with interferential therapy can significantly speed up colonic transit in children with slow transit constipation.

Gastro-oesophageal reflux in infants under 6 months with cystic fibrosis

AIM To establish the incidence of pathological gastro-oesophageal reflux (GOR) in newly diagnosed infants with cystic fibrosis and to identify clinical predictors of increased reflux. METHODS 26 infants with cystic fibrosis less than 6 months of age (14 male, 12 female; mean (SEM) age 2.1 (0.21) months, range 0.8 to 5.6 months) underwent prolonged oesophageal pH monitoring (mean duration 27.1 (0.49) hours; range 21.3 to 30.2 hours). Reflux symptoms, anthropometric variables, pancreatic status, meconium ileus, genotype, and chest x ray findings were correlated with pH monitoring data. RESULTS Five infants (19.2%) had an abnormal fractional reflux time of greater than 10%, seven (26.9%) of 5–10%, and 14 (53.8%) of below 5%. Infants who presented with frequent vomiting had a significantly higher fractional reflux time than infants who had infrequent or no vomiting. There was no significant association between abnormal chest x rays and pathological GOR. Sex, genotype, nutritional status, meconium ileus, and pancreatic enzyme supplementation were not significantly associated with pathological GOR. CONCLUSIONS About one in five newly diagnosed infants with cystic fibrosis had pathological GOR. Pathologically increased reflux was present before radiological lung disease was established. Apart from frequent vomiting, no useful clinical predictors of pathological reflux were found.

Bacteriophages in gut samples from pediatric Crohn's disease patients: metagenomic analysis using 454 pyrosequencing.

Background: The role of bacteriophage in Crohn’s disease (CD) is unknown. This study investigated the abundance of phages in ileal and colonic samples from pediatric CD patients and controls. Methods: Ileal and colonic biopsies from 6 CD patients, gut wash samples from 3 CD patients, and ileal biopsies from 6 noninflammatory bowel disease patients (controls) were analyzed for the presence of bacteriophage using 454 high-throughput pyrosequencing. A sequence-independent single-primer amplification method was used to amplify viral sequences. Results: A total of 186,143 high quality reads were obtained from the 4 sample populations. Contigs and sequence clusters (generated from unassembled singletons) were aligned with sequences from the National Center for Biotechnology Information viral reference database and analyzed by MEGAN. The largest number of viral hits was obtained from the CD gut wash samples (n = 691), followed by CD ileal samples (n = 52), control ileum samples (n = 20), and CD colonic samples (n = 1). The most abundant virus sequences identified belonged to the Caudovirales phage. Conclusions: Our study characterized a diverse phage community in the gut of CD patients. In this study, we have identified differences in phage composition between CD patients and control individuals. The large abundance of phages in CD ileum tissue and CD gut wash sample suggests a role of phage in CD development. The role of phage dysbiosis in CD is currently unknown but opens up a new area of research.