The feasibility of wireless capsule endoscopy in detecting small intestinal pathology in children under the age of 8 years: a multicentre European study.

Objective: To systematically evaluate the feasibility and methodology to carry out wireless capsule endoscopy (WCE) in children <8 years to define small intestinal pathology. Design: Prospective European multicentre study with negative prior investigation. Patients and interventions: 83 children aged 1.5–7.9 years were recruited. Initially, all were offered “swallowing” (Group 1) for capsule introduction. If this failed endoscopic placement (Group 2) was used and the Roth net, Advance or custom-made introducers were compared. Outcome measures: Primary endpoint: to determine pathology; secondary endpoint: comparison of capsule introduction methods. Results: Capsule introduction: 20 (24%) children aged 4.0–7.9 years (mean, 6.9 years; 14 male) comprising Group 1 were older (p<0.025) than 63 (76%) aged 1.5–7.9 years (mean, 5.25 years; 30 male) forming Group 2. Complications: Roth net mucosal trauma in 50%; no others occurred. The available recording apparatus was inappropriate for those <3 years. Indications: gastrointestinal bleeding: n = 30 (16 positive findings: four ulcerative jejunitis, four polyps, two angiodysplasia, two blue rubber blebs, two Meckel’s diverticula, one anastomotic ulcer, one reduplication); suspected Crohn’s disease: n = 20 (11 had Crohn’s disease); abdominal pain: n = 12 (six positive findings: three Crohn’s disease, two lymphonodular hyperplasia, one blue rubber bleb); protein loss: n = 9 (four lymphangectasia); malabsorption: n = 12 (seven positive findings: six enteropathy, one ascaris). No abnormalities overall: 45%. Conclusion: WCE is feasible and safe down to the age of 1.5 years. 20 children >4 years swallowed the capsule. The Advance introducer proved superior for endoscopic placement. The pathologies encountered showed age specificity and, unlike in adolescents, obscure gastrointestinal bleeding was the commonest indication

Colonic Involvement in a Patient with Chronic Lymphocytic Leukaemia

Various gastrointestinal infiltrations have been described in patients with chronic lymphocytic leukaemia (CLL). Here, we report a 69-year-old man with CLL and anaemia in whom the macroscopic finding of colonoscopy was normal, but the histological specimens revealed lymphocytic leukemia in ileum and in colon. If a CLL patient has any symptoms suggesting a possible GI manifestation of the haematologic disease or anaemia not explained by bone marrow infiltration or hemolysis, the diagnostic evaluation should include endoscopies with adequate biopsies

FOXP3(+) T cells are present in kidney biopsy samples in children with tubulointerstitial nephritis and uveitis syndrome

Tubulointerstitial nephritis (TIN) is an inflammatory disease of unknown pathogenesis. To evaluate a possible role of regulatory T cells (Tregs) in the pathophysiology of TIN with (TINU) and without uveitis, we investigated the presence and quantity of FOXP3(+) T regulatory lymphocytes in diagnostic kidney biopsies from pediatric patients. A total of 33 patients (14 TIN and 19 TINU) were enrolled. The quantity of CD4(+), FOXP3(+) and double-positive T cells in formalin-fixed kidney biopsies was determined using double label immunohistochemistry with anti-human CD4 and FOXP3 antibodies. FOXP3 staining was successful in all 33 patients. In patients with chronic uveitis, the density of FOXP3(+) cells was significantly lower (p = 0.046) than in TIN patients without uveitis or with uveitis lasting <3 months. CD4(+) staining was successful in 23 patients. The density of all lymphocytes (CD4(+), CD4(+)FOXP3(+) and FOXP3(+) cells) was significantly lower (p = 0.023) in patients with chronic uveitis than in other patients. FOXP3(+) T cells are present in kidney biopsy samples from TIN and TINU patients. In patients with chronic uveitis, the density of FOXP3(+) T cells is significantly lower than in other patients, suggesting a different pathomechanism for these clinical conditions.Peer reviewe

Variations in pigment and carbohydrate content of gallbladder bile affect accurate quantitation of total protein when using the fluorescamine method

Background: Despite solute dilution and reduced total lipid concentrations, an unexplained increase in protein concentration has been reported to occur in the gallbladder bile of cholesterol gallstone patients. Methods: Solutes in gallbladder bile from gallstone-free controls and from four study groups were measured using standard methods. Total proteins were measured using amino acid analysis and a conventional fluorescamine method. Results: Bile salts and pigment content were greater in gallstone-free controls than in all other study groups, including morbidly obese gallstone-free subjects. Total biliary protein concentration, as determined by amino acid analysis in the gallstone-free control group was higher than in non-obese gallstone patients with multiple stones and in morbidly obese gallstone-free subjects. Total biliary proteins as measured with fluorescamine, however, did not show intergroup differences. A major problem of the conventional fluorescamine assay is shown to be an artefact arising from the high pigment content of the more concentrated samples. Conclusions: Very dilute gallbladder bile samples are often found in the presence of gallstone disease. This also occurs in morbidly obese subjects, even in the absence of gallstones. Although the contribution of protein secretion/absorption by the gallbladder can also be relevant, especially in the presence of morbid obesity, the protein concentration in gallbladder bile, when accurately measured, generally parallels the concentrations of non-absorbed biliary solutes, reflecting the efficiency of fluid absorption. Measurement of biliary proteins by the conventional fluorescamine method is unreliable in clinical studies in which intergroup differences in pigment content are commonly present

Maternal Use of Antibiotics, Hospitalisation for Infection during Pregnancy, and Risk of Childhood Epilepsy: A Population-Based Cohort Study

BACKGROUND: Maternal infection during pregnancy may be a risk factor for epilepsy in offspring. Use of antibiotics is a valid marker of infection. METHODOLOGY/PRINCIPAL FINDINGS: To examine the relationship between maternal infection during pregnancy and risk of childhood epilepsy we conducted a historical cohort study of singletons born in northern Denmark from 1998 through 2008 who survived ≥29 days. We used population-based medical databases to ascertain maternal use of antibiotics or hospital contacts with infection during pregnancy, as well as first-time hospital contacts with a diagnosis of epilepsy among offspring. We compared incidence rates (IR) of epilepsy among children of mothers with and without infection during pregnancy. We examined the outcome according to trimester of exposure, type of antibiotic, and total number of prescriptions, using Poisson regression to estimate incidence rate ratios (IRRs) while adjusting for covariates. Among 191,383 children in the cohort, 948 (0.5%) were hospitalised or had an outpatient visit for epilepsy during follow-up, yielding an IR of 91 per 100 000 person-years (PY). The five-year cumulative incidence of epilepsy was 4.5 per 1000 children. Among children exposed prenatally to maternal infection, the IR was 117 per 100,000 PY, with an adjusted IRR of 1.40 (95% confidence interval (CI): 1.22-1.61), compared with unexposed children. The association was unaffected by trimester of exposure, antibiotic type, or prescription count. CONCLUSIONS/SIGNIFICANCE: Prenatal exposure to maternal infection is associated with an increased risk of epilepsy in childhood. The similarity of estimates across types of antibiotics suggests that processes common to all infections underlie this outcome, rather than specific pathogens or drugs

Self-Assemblage and Quorum in the Earthworm Eisenia fetida (Oligochaete, Lumbricidae)

Despite their ubiquity and ecological significance in temperate ecosystems, the behavioural ecology of earthworms is not well described. This study examines the mechanisms that govern aggregation behaviour specially the tendency of individuals to leave or join groups in the compost earthworm Eisenia fetida, a species with considerable economic importance, especially in waste management applications. Through behavioural assays combined with mathematical modelling, we provide the first evidence of self-assembled social structures in earthworms and describe key mechanisms involved in cluster formation. We found that the probability of an individual joining a group increased with group size, while the probability of leaving decreased. Moreover, attraction to groups located at a distance was observed, suggesting a role for volatile cues in cluster formation. The size of earthworm clusters appears to be a key factor determining the stability of the group. These findings enhance our understanding of intra-specific interactions in earthworms and have potential implications for extraction and collection of earthworms in vermicomposting processes

Histamine Derived from Probiotic Lactobacillus reuteri Suppresses TNF via Modulation of PKA and ERK Signaling

Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liquid chromatography-high performance liquid chromatography (HILIC-HPLC) separation isolated TNF-inhibitory compounds, and HILIC-HPLC fraction composition was determined by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from L-histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in production of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed TNF production via activation of the H2 receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA) and resulted in suppression of TNF production by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, L-histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF production. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases