Colonic Mucosal Microbiota and Association of Bacterial Taxa with the Expression of Host Antimicrobial Peptides in Pediatric Ulcerative Colitis.

Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), are chronic debilitating disorders of unknown etiology. Over 200 genetic risk loci are associated with IBD, highlighting a key role for immunological and epithelial barrier functions. Environmental factors account for the growing incidence of IBD, and microbiota are considered as an important contributor. Microbiota dysbiosis can lead to a loss of tolerogenic immune effects and initiate or exacerbate inflammation. We aimed to study colonic mucosal microbiota and the expression of selected host genes in pediatric UC. We used high-throughput 16S rDNA sequencing to profile microbiota in colonic biopsies of pediatric UC patients (n = 26) and non-IBD controls (n = 27). The expression of 13 genes, including five for antimicrobial peptides, in parallel biopsies was assessed with qRT-PCR. The composition of microbiota between UC and non-IBD differed significantly (PCoA, p = 0.001). UC children had a decrease in Bacteroidetes and an increase in several family-level taxa including Peptostreptococcaceae and Enterobacteriaceae, which correlated negatively with the expression of antimicrobial peptides REG3G and DEFB1, respectively. Enterobacteriaceae correlated positively with the expression siderophore binding protein LCN2 and Betaproteobacteria negatively with DEFB4A expression. The results indicate that reciprocal interaction of epithelial microbiota and defense mechanisms play a role in UC.

Detailed Follow-up Study of Pediatric Orofacial Granulomatosis Patients.

OBJECTIVES: Orofacial granulomatosis (OFG) is a chronic inflammatory condition affecting the orofacial area. Its connection to Crohn disease (CD) is debated. Our aim was to describe a cohort of pediatric patients with OFG in detail, study the long-term behavior of OFG, and evaluate factors predicting CD in patients with OFG. METHODS: We invited patients diagnosed with OFG at 2 university hospitals, Finland for a follow-up appointment. Patients (n = 29) were examined by a dentist and an otorhinolaryngologist using a structural schema. Orofacial findings were also recorded using digital photographing. Patients filled in questionnaires about general health and special diets. Patients' nutrition was evaluated from food records. The findings were compared between patients with OFG only and OFG with CD. RESULTS: Patients with CD had more findings in the orofacial area (total score for orofacial findings median 11) compared to patients with OFG only (total score median 7.5). There was no statistically significant difference in the type of lesions between these groups, except the upper lip was more often affected in patients with CD (n = 11) than in patients with OFG only (n = 0). Most of the patients had normal otorhinolaryngological findings. All patients with elevated anti-Saccharomyces cerevisiae antibody A levels had CD (n = 6) and they presented with more orofacial findings (total score) than patients with normal levels of anti-S cerevisiae antibody A (P = 0.0311). CONCLUSIONS: Long-term follow-up of pediatric-onset patients with OFG shows good prognosis. Patients with OFG do not seem to have otorhinolaryngological comorbidity. Anti-S cerevisiae antibody A may serve as a factor to indicate the possible presence of underlying CD in patients with OFG, but further studies are requested.

A Prospective Study on the Usefulness of Duodenal Bulb Biopsies in Celiac Disease Diagnosis in Children: Urging Caution.

OBJECTIVES: Several recent celiac disease guidelines recommend the acquisition of duodenal bulb biopsies for diagnostics. This is in conflict with previously reported evidence and routine practice from the 1960s onward. We reopened the issue in a prospective multicenter study and used morphometric variables in evaluating the usefulness of bulb biopsies in children. We further sought to establish whether deposits of IgA targeting bulb transglutaminase 2 (TG2) could be of diagnostic help. METHODS: Diagnoses of celiac disease were based on clinic and distal duodenal histopathology statements. Centralized reading of villous height (VH) to crypt depth (CrD) ratios and IgA deposits was performed on anatomical duodenal bulb specimens. All children participating also underwent routine investigations for other diseases. RESULTS: Twenty-two children had celiac disease, and another 22 served as non-celiac disease controls. The quality of the anatomical bulb specimens was unsatisfactory for reliable morphometric measurements in 20 out of 44 (45%) patients even after recuttings. All celiac disease patients had VH:CrD<2.0 (mean 0.2) but also 10 out of 13 (77%) non-celiac control patients had an injured bulb mucosal lining (mean 1.3) even up to false-positive "flat lesion". Bulb IgA deposits were able to separate celiac disease from disease controls. CONCLUSIONS: Morphological injury is common in the anatomical bulb even without celiac disease, increasing the risk of false-positive diagnoses. Premature conclusions might have been drawn on current care guidelines as to celiac disease diagnosis based solely on anatomical bulb specimens. Bulb mucosal IgA targeting TG2 in poor quality biopsy specimens is a powerful clinical tool in finding celiac disease patients.

Presentation of Celiac Disease in Finnish Children Is No Longer Changing: A 50-Year Perspective.

OBJECTIVES: To chart trends in the presentation of celiac disease in a large cohort of Finnish children diagnosed over a period of 48 years. STUDY DESIGN: Clinical and serologic data, severity of small-bowel mucosal damage, and presence of associated conditions were gathered from 596 children diagnosed with celiac disease in 1966-2013. The children were divided into 4 groups based on the year of diagnosis (before 1980, 1980-1999, 2000-2009, and 2010-2013), and the variables were compared between the periods. The incidence of celiac disease autoimmunity in 2001-2013 was calculated based on the number of new antibody-positive cases in each year. RESULTS: Age at diagnosis rose from median 4.3 years before 1980 to between 7.6 and 9.0 years in the later periods. The severity of clinical presentation, in general, became milder and poor growth less common during the entire study period of 50 years. Percentages of children with classical gastrointestinal presentation decreased, and those with atypical or subclinical presentation increased after the 1990s, these changes leveling off in 2000-2013. Similarly, the severity of small-bowel mucosal damage was milder after the 1990s. The incidence of celiac disease autoimmunity increased in the early 2000s but then fluctuated without a clear trend. There were no significant secular changes in sex distribution, presence of anemia, levels of celiac antibodies, or celiac disease-associated conditions. CONCLUSIONS: The clinical and histologic presentation of celiac disease in children became milder, especially in the 1980s and 1990s. However, most of these changes have reached a plateau in recent years.

Parenteral plant sterols and intestinal failure-associated liver disease in neonates.

OBJECTIVES: We prospectively evaluated incidence of prolonged (>28 days) parenteral nutrition (PN), associated complications, and significance of parenteral plant sterols (PS) in neonatal intestinal failure-associated liver disease (IFALD) compared with children. METHODS: We recruited 28 neonates (mean age 50 days, range 28-126) and 11 children (6.9 y, 2.1-16.6) in all of Finland. Patients underwent repeated measurements of serum cholesterol, noncholesterol sterols, including PS, cholestanol and cholesterol precursors, and liver biochemistry during and 1 month after discontinuation of PN. Healthy matched neonates (n=10) and children (n=22) served as controls. RESULTS: IFALD occurred more frequently among neonates (63%) than children (27%; P<0.05). Ratios of serum PS, including stigmasterol, sitosterol, avenasterol, and campesterol, and total PS were increased among neonates compared with healthy controls and children on PN by 2- to 22- and 2- to 5-fold (P<0.005), respectively. Neonates with IFALD had significantly higher ratios of serum PS and cholestanol compared with neonates without IFALD (P<0.05). Total duration of PN associated with serum cholestanol, stigmasterol, avenasterol, alanine aminotransferase, and aspartate aminotransferase (r=0.472-0.636, P<0.05). Cholestanol and individual serum PS, excluding campesterol, reflected direct bilirubin (r=0.529-0.688, P<0.05). IFALD persisted after discontinuation of PN in 25% of neonates with 4.2- and 2.2-times higher ratios of serum stigmasterol and cholestanol compared with neonates without IFALD (P<0.05). CONCLUSIONS: Frequent occurrence of IFALD among neonates on PN displays an association to duration of PN and markedly increased serum PS, especially stigmasterol, in comparison to healthy neonates and children on PN. Striking accumulation of parenteral PS may contribute to IFALD among neonates.

[Eosinophilic diseases of the gastrointestinal tract]. / Ruoansulatuskanavan eosinofiiliset sairaudet.

Eosinophilic esophagitis, gastroenteritis and colitis are very likely underdiagnosed conditions, and their actual incidence may be increasing. The diagnosis and treatment remain, however, fairly poorly established and are based on inadequate scientific evidence. Differential diagnosis is broad, mainly conditions causing secondary eosinophilia, such as allergies. If the secondary causes have been carefully excluded, the possibility of rare hypereosinophilic syndrome should be considered in prolonged eosinophilia.

[Mastocytosis as the cause of childrens' abdominal discomforts]. / Mastosytoosi lasten vatsavaivojen aiheuttajana.

In mastocytosis the number of mast cells is increased, and the most common manifestation is urticaria pigmentosa. We describe four children, of which two developed ulceration of the upper gastrointestinal tract. Main symptoms in the other children were vomiting, heartburn and abdominal pains, which were manifested as intense crying spells. The symptoms are caused by mediators such as histamine being released from the mast cells, and blockers of the histamine receptor thus play a central role in their treatment. The childrens' condition was significantly alleviated by adequate medication: the ulceration healed, symptoms were relieved and growth was normalized.

Efficacy and safety of granulocyte, monocyte/macrophage adsorptive in pediatric ulcerative colitis.

AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis. METHODS: The ADAPT study was a prospective, open-label, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric ulcerative colitis activity index (PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn(®) granulocyte, monocyte/macrophage adsorptive (GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint was the change in mean PUCAI between baseline and week 12; the secondary endpoint was improvement in PUCAI categorized as (Significant Improvement, PUCAI decrease of ≥ 35), Moderate Improvement (PUCAI decrease of 20 < 35), Small Improvement (PUCAI decrease of 10 < 20) or No change (PUCAI decrease of < 10). RESULTS: Twenty-five patients (mean age 13.5 years; mean weight 47.7 kg) were enrolled. In the intention-to-treat set (ITT), the mean value for PUCAI improvement was 22.3 [95%CI: 12.9-31.6; n = 21]. In the per-protocol (PP) set, the mean improvement was 36.3 [95%CI: 31.4-41.1; n = 8]. Significant Improvement was recorded for 9 out of 20 patients (45%); 5 out of 20 patients (25%) had Moderate Improvement and one patient (5%) had No Change in PUCAI score at week 12. In the PP set, six out of eight patients (75%) showed Significant Improvement; and in two out of eight patients (25%) Moderate Improvement was recorded. The endoscopic activity index (EAI) decreased by 3 points on average. Seven (7) out of 21 (33%) patients in ITT and 4 out of 8 (50%) patients in PP have used steroids during the clinical investigation. The mean steroid dosage for these patients in the ITT set decreased from a mean 12.4 mg to 10 mg daily on average from Baseline to week 12. CONCLUSION: Adacolumn(®) GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative Colitis. No new safety signals were reported. The present data contribute to considering GMA apheresis as a therapeutic option in pediatric patients having failed first line therapy.

Increased expression of CXCL16, a bacterial scavenger receptor, in the colon of children with ulcerative colitis.

BACKGROUND AND AIMS: CXCL16 is a scavenger receptor which has been connected to phagocytosis of bacterial antigens in experimental colitis. It has also been shown to have a pivotal role in the development of experimental colitis in mice. The increased expression of CXCL16 has been demonstrated in inflamed lesions of patients with Crohn disease. Our aim was to study the expression of CXCL16 in the colon of patients with ulcerative colitis. METHODS: Relative quantitative reverse transcription-polymerase chain reaction was applied to explore the gene expressions of CXCL16, its receptor CXCR6, and interleukin 8, an inflammatory marker, in the colonic biopsies of children with active ulcerative colitis (n=19), children with ulcerative colitis in remission (n=9) and children with no inflammatory condition in colon (n=14). RESULTS: An increased expression of CXCL16 in the colonic biopsies of children with ulcerative colitis was found both in active disease (p=0.006) and in remission (p=0.033), when compared to children without inflammatory condition. The gene expressions of interleukin 8 and CXCL16 correlated with each other (rs=0.67, p=0.01). The expression of CXCR6 mRNA was comparable between the study groups (p=0.50). CONCLUSIONS: The gene expression of CXCL16 was increased in patients with ulcerative colitis both in active disease and in remission suggesting an important role of the molecule in the pathogenesis of the condition.

Surgical treatment and outcomes of severe pediatric intestinal motility disorders requiring parenteral nutrition.

AIM: The aim of this study was to characterize outcomes of children with severe intestinal motility disorders (IMD) requiring parenteral nutrition (PN). METHODS: Twenty consecutive children with primary IMD requiring long-term PN between 1984 and 2010 were included. Median (interquartile range) follow-up was 13.1 (5.2-20.1) years. Treatment, PN dependence, growth, nutritional status, liver function, and survival were assessed. RESULTS: Underlying etiology included chronic intestinal pseudo obstruction (CIPO; n=8) and Hirschsprung disease with extensive aganglionosis (n=12). CIPO and aganglionosis patients had 100 (86-100%) and 29 (19-40%) of age-adjusted small bowel length remaining, respectively. In order to facilitate enteral tolerance and avoid PN-associated liver disease, short aganglionic segment (40 cm) was left in situ in four of five cases, with aganglionosis extending to duodenojejunal flexure combined with Ziegler myectomy-myotomy in two. Six of seven children with aganglionosis extending into mid small intestine underwent staged jejunoanal pull-through. Feeding/venting gastrostomies (n=13) or jejunostomies were commonly employed. Probability of PN dependence owing to IMD was markedly increased in relation to short bowel syndrome (70 versus 19% at 5 years, P<0.0001). Two (10%) patients developed end-stage liver disease. A total of 11 (55%) patients (5 CIPO and 6 aganglionosis) weaned off PN after 8.2 years (1.8-17 years), including two patients after intestinal transplantation (ITx). Two children died before ITx-era giving overall survival of 90%. Survivors had well-preserved liver function, growth, and nutritional status. CONCLUSIONS: Despite high PN dependence, long-term survival is achievable in the majority of children with IMD requiring PN. A wide repertory of surgical options including ITx is required for optimal outcomes.

Erythrocyte concentrations of metabolites or cumulative doses of 6-mercaptopurine and methotrexate do not predict liver changes in children treated for acute lymphoblastic leukemia.

BACKGROUND: During therapy consisting of 6MP and MTX, metabolites accumulate in the erythrocytes. The erythrocyte levels of metabolites reflect the intensity of therapy. Whether they are associated with hepatotoxicity manifested as histological liver changes is not known. We studied the association of the metabolites and cumulative doses of 6MP and MTX with histological liver disease. METHODS: Serial measurements of E-TGN, E-MTX, and ALT during maintenance therapy were performed and cumulative doses of 6MP and MTX were calculated as g/m2 in 16 children with ALL. Each subject underwent a percutaneous liver biopsy at the end of therapy to screen for histological liver disease. RESULTS: No differences in E-TGN, E-MTX, or cumulative doses of 6MP or MTX were detected in the children with ALL with liver fibrosis compared to those without fibrosis, or in the children with less liver fatty change compared to those with more fatty change. Serum median ALT levels correlated significantly positively with cumulative doses of 6MP during therapy (rS = 0.527, P = 0.036), but not with cumulative doses of MTX, or E-TGN, or E-MTX. CONCLUSIONS: Erythrocyte levels of the metabolites or the cumulative doses of 6MP and MTX do not predict histological liver disease in children treated for ALL.

Rectal bleeding in infancy: clinical, allergological, and microbiological examination.

OBJECTIVE: Rectal bleeding is an alarming symptom and requires additional investigation. In infants it has been explained mainly by hypersensitivity. In addition to dietary antigens, intraluminal microbial agents challenge the immature gut mucosa. Although controlled in the mature gut, these antigens may induce inflammation in the developing gastrointestinal tract. The objectives of this study were to evaluate prospectively the clinical course of rectal bleeding and evaluate the impact of cow's milk allergy and aberrant gut microbiota on the condition. Because withdrawal of cow's milk antigens from the infants' diet is used as a first treatment without evidence of its efficacy, we also aimed to asses the effect of a cow's milk-elimination diet on the duration of rectal bleeding. METHODS: The study involved 40 consecutive infants (mean age: 2.7 months) with visible rectal bleeding during a 2-year period at the Tampere University Hospital Department of Pediatrics. Most of the infants (68%) were fully breastfed. At enrollment the infants were randomly allocated to receive a cow's milk-elimination diet (n = 19) or continue their previous diet (n = 21) for 1 month. Findings of colonoscopy, fecal bacterial culture, fluorescence in situ hybridization of selected gut genera, specific detection of fecal enteroviruses, rotaviruses, and adenoviruses, fecal electron microscopy for viruses, and mucosal electron microscopy for viruses were assessed. During each visit the severity of atopic eczema, if any, was assessed according to the SCORAD method. In evaluating the extent of sensitization, serum total immunoglobulin E (IgE) and specific IgE and skin-prick tests for cow's milk, egg, and wheat were studied. Cow's milk allergy was diagnosed by elimination and provocation testing. Five patients were hospitalized; all others were treated on an outpatient basis. The follow-up visits were scheduled 1 month later and at the age of 1 year. Sixty-four healthy reference infants were selected as controls according to the following criteria: age and timing of fecal sampling being identical to within 1 month. RESULTS: Altogether, 32 (80%) infants manifested bloody stools during follow-up (mean [range]: 2.1 [1-15] per day). The mean number of days with rectal bleeding on follow-up was 6. Typically, bloody stools occurred irregularly, for which reason the mean time to the last occurrence of rectal bleeding was 24 (range: 1-85) days from admission. Atopic eczema at presentation or during follow-up was diagnosed in 38% of the infants. Increased specific IgE concentrations or a positive skin-prick test were uncommon. The growth of the infants was normal on admission and during follow-up. Colonoscopy revealed typically focal mucosal erythema and aphthous ulcerations. The mucosa appeared normal in less than half of the patients. No anorectal fissures or colonic polyps were found. Light microscopy revealed that the overall architecture of the mucosa was well maintained. Acute inflammation or postinflammatory state and focal infiltration of eosinophils in the lamina propria were the most common abnormalities. A cow's milk-elimination diet did not affect the duration of rectal bleeding. Cow's milk allergy was diagnosed in 7 (18%) patients. Virus-particle aggregates were found in the microvillus layer of the colon epithelium in 8 cases. The surface epithelium of the virus-positive colon biopsy specimens regularly showed degenerative changes in the microvillus layer and epithelial cells. Electron microscopy study of the colon biopsies disclosed virus particles (30 nm in diameter) on the surface of epithelial cells. Virus particles or RNA were present in feces in only a minority of the patients. All fecal cultures were negative for Salmonella, Shigella, and Yersinia. Campylobacter jejuni was found in the feces of 1 patient, and fecal cultures were positive for Clostridium difficile in 4 patients, Staphylococcus aureus in 8 patients, and yeast in 2 patients. Fluorescence in situ hybridization revealed that at the time of admission the total numbers of bacteria and the numbers of bifidobacteria and lactobacilli in feces were lower in the patients compared with controls. The fecal concentrations of microbes characterized in this study (Bacteroides, bifidobacteria, Clostridium, lactobacilli, and enterococci) did not differ significantly between the time of admission and the second visit in the patients or controls. At the age of 1 year, 7 patients still suffered from cow's milk allergy, 5 of whom also suffered from multiple food allergies. Atopic eczema and histopathologically confirmed inflammation of the colonic mucosa at presentation were associated with persistence of cow's milk allergy at the age of 1 year. No patients exhibited gastrointestinal complaints or visible blood in stools. CONCLUSIONS: Rectal bleeding in infants is generally a benign and self-limiting disorder. Bloody stools occurred irregularly for only a few days during the following months. As in a previous report, most infants were exclusively breastfed. In the majority of the patients the cause of the condition remains unknown. An association with viruses can be seen in some patients. The microbes that commonly lead to bloody diarrhea in older children and adults, Salmonella, Shigella, and Yersinia, were absent in the present material. The low bifidobacterial numbers in fecal samples may indicate a significant aberrance that may provide a target for probiotic intervention to normalize gut microbiota. The gut microbiota overall seemed stable, because the numbers of major groups of microbiota tested did not change significantly between the time of admission and after 1 month. Cow's milk allergy among these patients is more uncommon than previously believed. Cow's milk challenge is thus essential in infants who become symptom-free during a cow's milk-free diet to reduce the number of false-positive cow's milk-allergy diagnoses.

Characterization of breast milk received by infants with gross blood in stools.

OBJECTIVE: The aim of this study was to ascertain factors that might be protective of the appearance of gross blood in the stools of breast-fed infants. METHODS: Logistic regression models were formed to search for variables possibly explaining the condition. In addition to the analyzed breast milk factors, mother's allergic disease was introduced into the models to control for its possible confounding effect. The breast milk samples, collected from mothers of infants with gross blood in stools (n = 23) and from mothers of healthy age-matched infants (n = 71), were analyzed for concentrations of transforming growth factor-beta2, tumor necrosis factor-alpha, interleukin (IL)-4, IL-10, prostaglandin (PG)E2, cysteinyl leukotrienes (Cys-LTs) and fatty acid composition. RESULTS AND CONCLUSIONS: Increase in the concentrations of PGE2 and Cys-LTs in the breast milk together with mother's allergic disease reduced the likelihood of gross blood in stools in the breast-fed infant. The results suggest that no single factor, but a combination of immunomodulatory factors may protect the child from gross blood in the stools of breast-fed infants. Allergic disease was not a risk factor as mother's allergic disease appeared to counterbalance the gross blood in stools. Due to the preliminary nature of the study, the results need to be verified in a larger setting. The challenge for the future lies in identifying of such active compounds for dietary modification to enforce particularly the properties of the breast milk which are immunoprotective for the infant and to reduce the likelihood of intestinal disorders in at risk infants.

Celiac disease: from inflammation to atrophy: a long-term follow-up study.

OBJECTIVES: Celiac disease develops gradually from lymphocytosis, crypt hyperplasia and minor villous atrophy to overt villous atrophy. It IS NOT known how such minor mucosal changes predict eventual celiac disease. The aim of this study was to evaluate the role of intraepithelial lymphocytosis and marginally decreased villous height/crypt depth ratio in the development of overt villous atrophy in a long-term follow-up. METHODS: The authors evaluated 980 small bowel biopsies of children who had previously been studied and found to be histologically negative for celiac disease between 1976 and 1992. Villous height/crypt depth ratio and the number of intraepithelial lymphocytes were measured in these initial biopsies. Cases with slight biopsy changes were identified for further study and sex and age matched subjects with normal biopsies from same group were selected as controls. They all were asked to submit serum samples for gliadin, endomysial and tissue transglutaminase antibodies 8 to 28 years after the initial biopsy. Those with positive screening tests were asked to undergo endoscopy and small intestinal biopsy. RESULTS: 236 cases with slight changes were identified, and 236 with normal mucosa served as controls; 76 cases and 68 controls participated in the follow-up study. Ten individuals had positive screening test results. Two new celiac disease patients, one in each group, were found. Four patients in the case group had been diagnosed with celiac disease by routine procedures during the follow-up. Thus, five cases and one control had developed celiac disease. CONCLUSIONS: Small bowel mucosal lymphocytosis or slight reduction in villous height/crypt depth ratio are common findings in patients with suspicion of celiac disease. These findings alone are poor predictors of celiac disease.

Lymphonodular hyperplasia of the terminal ileum associated with colitis shows an increase gammadelta+ t-cell density in children.

OBJECTIVE: Recently we reported a close association between lymphonodular hyperplasia (LNH) of the bulb of the duodenum and increased densities of intraepithelial gammadelta+ T-cells in subjects with untreated food allergies. In this study we sought to determine whether children with LNH of the terminal ileum (TI) show a similar correlation. METHODS: The mucosal specimens taken by colonoscopy from the TIs of 22 children with LNH of the TI without colitis, 13 with right-sided colitis or pancolitis, nine with left-sided colitis, eight with Crohn's disease, and three endoscopically healthy subjects were studied for T-cell subsets with monoclonal antibodies using a three-layer peroxidase staining method. RESULTS: LNH of the TI was found in 32 of the 55 subjects (58%). In 22 it was the only endoscopic finding, but in nine of 13 subjects (69%) it was related to right-sided colitis or pancolitis. In patients with left-sided colitis or Crohn's disease it was diagnosed only rarely. In the whole study population, LNH of the of the TI showed a significant association with the increment in the density of gammadelta+ T-cells. The subjects with LNH of the TI and colitis starting from the cecum showed the highest values, discriminating them statistically from any other study group. Accordingly their gammadelta+/CD3+ ratio was high. Even in the subjects with LNH of the TI without colitis, the increment in gammadelta+ T-cells was significant as compared with the subjects with left-sided colitis. Upregulations of D-related expression on the mucosa of the TI were similar regardless of the presence of LNH or colitis or an increment in gammadelta+ T-cells. CONCLUSION: Our preliminary observations showed increased densities of intraepithelial gammadelta+ T-cells and elevated gammadelta+/CD3+ ratios in subjects with LNH on the mucosa of the TI, especially if related to colitis starting at the cecem, but not in subjects with typical left-sided colitis or granulomatous Crohn's disease. The study also provides further evidence suggesting the significance of food-borne antigens in the pathogenetic mechanism of right-sided colitis or pancolitis. The finding also indicates the significance of classifying colitis into gammadelta-positive and -negative diseases, and has implications for the treatment of these entities.

Acquired myopathic intestinal pseudo-obstruction may be due to autoimmune enteric leiomyositis.

We describe a previously healthy boy who developed intestinal pseudo-obstruction following an episode of gastroenteritis at age 2 years. At presentation, the patient had mildly raised erythrocyte sedimentation rate and C-reactive protein level, and elevated antineutrophil cytoplasmic antibodies, antinuclear anti-DNA, and anti-smooth muscle antibodies. His electrogastrography was myopathic with no dominant frequency. First full-thickness intestinal biopsies showed a T lymphocytic myositis, particularly in the circular muscle. Steroid therapy resulted in clinical remission; cessation of steroids, in relapse. Further full-thickness biopsies showed an initial reduction in alpha-smooth muscle actin immunostaining in circular muscle myocytes and later atrophy and disappearance of many myocytes. Vascular and the remaining enteric smooth muscle cells showed HLA-DR and intercellular adhesion molecule 1 expression. These observations demonstrate the ability of enteric myocytes to take part in an inflammatory response and to change their phenotype, allowing them to act as antigen-presenting cells and to activate T cells. This and possible cytokine production by the myocytes play a role in their own destruction. This process responded to immunosuppressive therapy.

Symptomatic response to Helicobacter pylori eradication in children with recurrent abdominal pain: double blind randomized placebo-controlled trial.

BACKGROUND: Controlled trials considering the effect of Helicobacter pylori (H. pylori) eradication on gastrointestinal symptoms in children are scant. We aimed to study the connection between recurrent abdominal pain and dyspepsia and H. pylori infection in children. STUDY: This was a double blind randomised controlled trial. Twenty children with recurrent abdominal pain (RAP) being H. pylori positive as measured with the C urea breath test (UBT) were randomized either to receive omeprazole, amoxycillin and clarithromycin (n = 10), or omeprazole and 2 placebos (n = 10) for 1 week after gastroscopy. Symptoms were registered prior to the treatment and at follow up visits 2, 6, 24, and 52 weeks after stopping the treatment. Control UBT was performed on all patients 6 weeks post-treatment and again at the 52 week follow-up visit, when also re-endoscopy with biopsies was done to all participants. RESULTS: All infected children had histologic gastritis. Bacterial eradication was achieved in 8/10 in the triple treatment group and in none in the placebo group. There was no change in symptom index in either group at 2 weeks post treatment. At 52 weeks a similar reduction in symptom index was observed in both groups irrespective of the healing of gastritis, which was more commonly achieved along the eradication. CONCLUSIONS: Bacterial eradication and healing of gastric inflammation does not lead to symptomatic relief of chronic abdominal pain in children.

Microbiota composition of the intestinal mucosa: association with fecal microbiota?

The fecal and mucosal microbiota of infants with rectal bleeding and the fecal microbiota of healthy age-matched controls were investigated by fluorescent in situ hybridization. Bifidobacteria were the main genus in both the feces and mucosa. The other genera tested, Bacteroides, Clostridium, Escherichia coli and lactobacilli/enterococci, represented only minor constituents. No differences in fecal microbiota were observed between patients and controls. In the patients, however, four times greater numbers of bifidobacteria were observed in the feces when compared to the mucosa. Notwithstanding this difference, a strong positive correlation prevailed for bifidobacteria in feces and mucosal samples. The genera assessed accounted for 16% of total bacterial counts on mucosal samples and for 47% of total bacterial counts in feces. This indicates that the unidentified part of the microbiota, especially on the mucosa, deserves more attention.