Excessive coupling of the salience network with intrinsic neurocognitive brain networks during rectal distension in adolescents with irritable bowel syndrome: a preliminary report.

BACKGROUND: The neural network mechanisms underlying visceral hypersensitivity in irritable bowel syndrome (IBS) are incompletely understood. It has been proposed that an intrinsic salience network plays an important role in chronic pain and IBS symptoms. Using neuroimaging, we examined brain responses to rectal distension in adolescent IBS patients, focusing on determining the alteration of salience network integrity in IBS and its functional implications in current theoretical frameworks. We hypothesized that (i) brain responses to visceral stimulation in adolescents are similar to those in adults, and (ii) IBS is associated with an altered salience network interaction with other neurocognitive networks, particularly the default mode network (DMN) and executive control network (ECN), as predicted by the theoretical models. METHODS: Irritable bowel syndrome patients and controls received subliminal and liminal rectal distension during imaging. Stimulus-induced brain activations were determined. Salience network integrity was evaluated by the functional connectivity of its seed regions activated by rectal distension in the insular and cingulate cortices. KEY RESULTS: Compared with controls, IBS patients demonstrated greater activation to rectal distension in neural structures of the homeostatic afferent and emotional arousal networks, especially the anterior cingulate and insular cortices. Greater brain responses to liminal vs subliminal distension were observed in both groups. Particularly, IBS is uniquely associated with an excessive coupling of the salience network with the DMN and ECN in their key frontal and parietal node areas. CONCLUSIONS & INFERENCES: Our study provided consistent evidence supporting the theoretical predictions of altered salience network functioning as a neuropathological mechanism of IBS symptoms.

Plasma-induced signatures reveal an extracellular milieu possessing an immunoregulatory bias in treatment-naive paediatric inflammatory bowel disease.

The inflammatory state associated with Crohn's disease (CD) and ulcerative colitis (UC) remains incompletely defined. To understand more clearly the extracellular milieu associated with inflammatory bowel disease (IBD), we employed a bioassay whereby plasma of treatment naive paediatric IBD patients (n = 22 CD, n = 15 UC) and unrelated healthy controls (uHC, n = 10) were used to induce transcriptional responses in a healthy leucocyte population. After culture, gene expression was measured comprehensively with microarrays and analysed. Relative to uHC, plasma of CD and UC patients induced distinct responses consisting, respectively, of 985 and 895 regulated transcripts [|log2 ratio| ≥ 0·5 (1·4-fold); false discovery rates (FDR) ≤ 0·01]. The CD:uHC and UC:uHC signatures shared a non-random, commonly regulated, intersection of 656 transcripts (χ(2)  = P < 0·001) and were highly correlative [Pearson's correlation coefficient = 0·96, 95% confidence interval (CI) = 0.96, 0.97]. Despite sharing common genetic susceptibility loci, the IBD signature correlated negatively with that driven by plasma of type 1 diabetes (T1D) patients (Pearson's correlation coefficient = -0·51). Ontological analyses revealed the presence of an immunoregulatory plasma milieu in IBD, as transcripts for cytokines/chemokines, receptors and signalling molecules consistent with immune activation were under-expressed relative to uHC and T1D plasma. Multiplex enzyme-linked immunosorbent assay (ELISA) and receptor blockade studies confirmed transforming growth factor (TGF)-ß and interleukin (IL)-10 as contributors to the IBD signature. Analysis of CD patient signatures detected a subset of transcripts associated with responsiveness to 6-mercaptopurine treatment. Through plasma-induced signature analysis, we have defined a unique, partially TGF-ß/IL-10-dependent immunoregulatory signature associated with IBD that may prove useful in predicting therapeutic responsiveness.

Validation of an instrument to measure quality of life in British children with inflammatory bowel disease.

OBJECTIVE: To validate IMPACT-III (UK), a health-related quality of life (HRQoL) instrument, in British children with inflammatory bowel disease (IBD). PATIENTS AND METHODS: One hundred six children and parents were invited to participate. IMPACT-III (UK) was validated by inspection by health professionals and children to assess face and content validity, factor analysis to determine optimum domain structure, use of Cronbach alpha coefficients to test internal reliability, ANOVA to assess discriminant validity, correlation with the Child Health Questionnaire to assess concurrent validity, and use of intraclass correlation coefficients to assess test-retest reliability. The independent samples t test was used to measure differences between sexes and age groups, and between paper and computerised versions of IMPACT-III (UK). RESULTS: IMPACT-III (UK) had good face and content validity. The most robust factor solution was a 5-domain structure: body image, embarrassment, energy, IBD symptoms, and worries/concerns about IBD, all of which demonstrated good internal reliability (α = 0.74-0.88). Discriminant validity was demonstrated by significant (P  < 0.05, P < 0.01) differences in HRQoL scores between the severe, moderate, and inactive/mild symptom severity groups for the embarrassment scale (63.7 vs 81.0 vs 81.2), IBD symptom scale (45.0 vs 64.2 vs 80.6), and the energy scale (46.4 vs 62.1 vs 77.7). Concurrent validity of IMPACT-III (UK) with comparable domains of the Child Health Questionnaire was confirmed. Test-retest reliability was confirmed with good intraclass correlation coefficients of 0.66 to 0.84. Paper and computer versions of IMPACT-III (UK) collected comparable scores, and there were no differences between the sexes and age groups. CONCLUSIONS: IMPACT-III (UK) appears to be a useful tool to measure HRQoL in British children with IBD.

Growth in children with Helicobacter pylori infection and dyspepsia.

AIMS: To compare the height, weight, and body mass index (BMI) of children presenting with dyspeptic symptoms and Helicobacter pylori infection, to those with dyspepsia but without the infection. METHODS: A retrospective chart review of 257 children was performed. 13C urea breath test was performed to detect H pylori infection; weight and height were recorded and BMI was calculated. Weight, height, and BMI SD scores were determined using the 1990 UK normative data. The Index of Multiple Deprivation 2004 (IMD 2004) scores, which measure deprivation at small area level, were calculated from the patients' postcodes. RESULTS: Ninety seven of the 257 children were H pylori positive. The mean age at diagnosis and presenting symptoms of H pylori positive and negative patients were similar. The mean IMD 2004 scores for children with H pylori infection were significantly higher compared to H pylori negative patients, suggesting that children with the infection came from relatively more deprived areas. The mean weight and height SD score were significantly lower for children with H pylori infection compared to those without. However, this difference was no longer significant after adjusting for socioeconomic deprivation and ethnic differences between the groups. CONCLUSION: Children with dyspepsia and H pylori infection were shorter and lighter than patients with similar symptoms but no infection. The differences in anthropometry may be due to socioeconomic and ethnic factors rather than H pylori infection.

Ileal manometry in children following ileostomies and pull-through operations.

Our aim was to analyse the patterns of ileal contractions in children. We reviewed the charts of 23 children who had ileal manometry studies (16 males), mean age 7 years (range 2 months to 17 years). We positioned the manometry catheters with 4-8 recording sites, 5 or 15 cm apart, through ileostomies fashioned for clinically indicated reasons. We studied six additional children with persistent faecal soiling following endorectal pull through for Hirschsprung's disease; the catheters were positioned through the anus and colon into the ileum. We recorded phasic and tonic intermittent contractions in all the subjects, clustered contractions (rate 5-9 min-1, duration 20-120 s) in 19 subjects with ileostomies and four with endorectal pull throughs. In 13 children there were prolonged propagated contractions, > 60 mmHg in amplitude, > 15 s in duration, propagating at rates of 2-6 cm s-1 over at least 20 cm. The migrating motor complex was rare; in 55 h of fasting recording there were two phase III sequences. There are four distinctive features of ileal manometry recordings in children: random intermittent contractions, clustered contractions, prolonged propagated contractions and tonic contractions. The features of ileal motility differ from motility in the proximal small bowel.