Capsule Endoscopy: A Valuable Tool in the Follow-Up of People With Celiac Disease on a Gluten-Free Diet

OBJECTIVES: Traditional celiac disease guidelines recommend follow-up endoscopy and duodenal biopsies at 6–12 months after commencing a gluten-free diet (GFD). However, histology may remain abnormal even 1–2 years later. We evaluated the role of capsule endoscopy in patients with celiac disease after treatment with a GFD. METHODS: Twelve adult patients with newly diagnosed celiac disease were prospectively enrolled. All patients had baseline symptom assessment, celiac serology (tissue transglutaminase antibody, tTG), and capsule endoscopy. Twelve months after commencing a GFD, patients underwent repeat symptom assessment, celiac serology, upper gastrointestinal endoscopy, and capsule endoscopy. RESULTS: At baseline, capsule endoscopy detected endoscopic markers of villous atrophy in the duodenum and extending to a variable distance along the small intestine. On the basis of small bowel transit time, the mean±s.e.m. percentage of small intestine with villous atrophy was 18.2±3.7%. After 12 months on a GFD, repeat capsule endoscopy demonstrated mucosal healing from a distal to proximal direction, and the percentage of small intestine with villous atrophy was significantly reduced to 3.4±1.2% (P¼0.0014) and this correlated with improvement in the symptom score (correlation 0.69, P¼0.01). There was a significant improvement in symptom score (5.2±1.0 vs. 1.7±0.4, P¼0.0012) and reduction in immunoglobulin A–tTG levels (81.5±10.6 vs. 17.5±8.2, P¼0.0005). However, 42% of subjects demonstrated persistent villous abnormality as assessed by duodenal histology. CONCLUSIONS: After 12 months on a GFD, patients with celiac disease demonstrate an improvement in symptoms, celiac serology, and the extent of disease as measured by capsule endoscopy. Mucosal healing occurs in a distal to proximal direction. The extent of mucosal healing correlates with improvement in symptoms. Duodenal histology does not reflect the healing that has occurred more distally.Ilmars Lidums, Edward Teo, John Field and Adrian G. Cummin

Amniotic fluid deficiency and congenital abnormalities both influence fluctuating asymmetry in developing limbs of human deceased fetuses

Fluctuating asymmetry (FA), as an indirect measure of developmental instability (DI), has been intensively studied for associations with stress and fitness. Patterns, however, appear heterogeneous and the underlying causes remain largely unknown. One aspect that has received relatively little attention in the literature is the consequence of direct mechanical effects on asymmetries. The crucial prerequisite for FA to reflect DI is that environmental conditions on both sides should be identical. This condition may be violated during early human development if amniotic fluid volume is deficient, as the resulting mechanical pressures may increase asymmetries. Indeed, we showed that limb bones of deceased human fetuses exhibited increased asymmetry, when there was not sufficient amniotic fluid (and, thus, space) in the uterine cavity. As amniotic fluid deficiency is known to cause substantial asymmetries and abnormal limb development, these subtle asymmetries are probably at least in part caused by the mechanical pressures. On the other hand, deficiencies in amniotic fluid volume are known to be associated with other congenital abnormalities that may disturb DI. More specifically, urogenital abnormalities can directly affect/reduce amniotic fluid volume. We disentangled the direct mechanical effects on FA from the indirect effects of urogenital abnormalities, the latter presumably representing DI. We discovered that both factors contributed significantly to the increase in FA. However, the direct mechanical effect of uterine pressure, albeit statistically significant, appeared less important than the effects of urogenital abnormalities, with an effect size only two-third as large. We, thus, conclude that correcting for the relevant direct factors allowed for a representative test of the association between DI and stress, and confirmed that fetuses form a suitable model system to increase our understanding in patterns of FA and symmetry development.Research Fund of the University of Antwerp, mobility grant from the Research Foundation – Flanders (FWO)

Evaluation of serum CEA, CYFRA21-1 and CA125 for the early detection of colorectal cancer using longitudinal preclinical samples

Blood-borne biomarkers for early detection of colorectal cancer (CRC) could markedly increase screening uptake. The aim of this study was to evaluate serum carcinoembryonic antigen (CEA), CYFRA21-1 and CA125 for the early detection of CRC in an asymptomatic cohort

Otitis Media in a New Mouse Model for CHARGE Syndrome with a Deletion in the Chd7 Gene

Otitis media is a middle ear disease common in children under three years old. Otitis media can occur in normal individuals with no other symptoms or syndromes, but it is often seen in individuals clinically diagnosed with genetic diseases such as CHARGE syndrome, a complex genetic disease caused by mutation in the Chd7 gene and characterized by multiple birth defects. Although otitis media is common in human CHARGE syndrome patients, it has not been reported in mouse models of CHARGE syndrome. In this study, we report a mouse model with a spontaneous deletion mutation in the Chd7 gene and with chronic otitis media of early onset age accompanied by hearing loss. These mice also exhibit morphological alteration in the Eustachian tubes, dysregulation of epithelial proliferation, and decreased density of middle ear cilia. Gene expression profiling revealed up-regulation of Muc5ac, Muc5b and Tgf-β1 transcripts, the products of which are involved in mucin production and TGF pathway regulation. This is the first mouse model of CHARGE syndrome reported to show otitis media with effusion and it will be valuable for studying the etiology of otitis media and other symptoms in CHARGE syndrome

T lymphocyte subsets in inflammatory bowel disease: peripheral blood.

Peripheral blood T lymphocytes and T lymphocyte subsets have been quantified in 28 patients with ulcerative colitis and 26 with Crohn's disease by an indirect immunofluorescence technique using monoclonal antibodies: OKT3, which detects all peripheral blood T lymphocytes; OKT4 (T cells of helper phenotype); and OKT8 (T cells of supressor-cytotoxic phenotype). Eighteen normal subjects and 16 patients with a variety of non-inflammatory gastrointestinal disorders were studied as controls. No significant differences were found between patient and control groups in the proportions of circulating T lymphocytes or their subsets. When compared with normal subjects, absolute numbers of T lymphocytes were reduced in patients with active ulcerative colitis or Crohn's disease (p less than 0.05). OKT4+ T cell numbers were reduced in ulcerative colitis, whether active (p less than 0.02) or inactive (p less than 0.05) and in active Crohn's disease (p less than 0.05) Numbers of OKT8+ T cells were reduced in active Crohn's disease (p less than 0.01). There were no differences in T lymphocyte numbers between the patient groups and the disease control subjects. The OKT4+:OKT8+ ratio in patients with inflammatory bowel disease did not differ from that in controls. No relation was found between any of the parameters studied and disease activity, site, or extent of disease, or treatment with sulphasalazine or corticosteroids. The presence of Ia-like, HLA-DR antigens on T cells was detected using a double marker immunofluorescence technique. In control subjects up to 7% of OKT3+ cells were HLA-DR+. In only three patients was the proportion of HLA-DR+ cells greater than in controls. These results indicate that the pathogenesis of ulcerative colitis or Crohn's disease does not depend upon an alteration in the proportion of circulating T lymphocytes nor upon an imbalance of T lymphocyte subsets as defined by monoclonal antibodies. The reduction in T lymphocyte numbers may result from mucosal infiltration. The findings also suggest that circulating T lymphocytes are not activated