TNFSF15 polymorphisms are associated with susceptibility to inflammatory bowel disease in a new European cohort.

OBJECTIVES: Inflammatory bowel disease (IBD), e.g., Crohn's disease (CD) and ulcerative colitis (UC), is a complex genetic disorder. Tumor necrosis factor (ligand) superfamily, member 15 (TNFSF15) has been previously identified as a susceptibility gene for CD in Japanese and UK cohorts. This replication study was designed in order to confirm and further validate the role of TNFSF15 in IBD. METHODS: A total of 666 IBD families (corresponding to 2,982 relatives) with European ancestry were genotyped for the rs6478108 and rs7869487 polymorphisms, which define the main TNFSF15 haplotypes previously associated with CD. An association between the main haplotypes and CD, UC and IBD was tested using the Genehunter TDT and Unphased statistics. Caspase recruitment domain 15 (CARD15)/TNFSF15 interaction and genotype/phenotype correlations were also studied. RESULTS: The previously reported "high-risk" haplotype (A) was associated with IBD (P=0.001) (OR=1.25 (1.05-1.50)) and CD (P=0.02) (OR=1.31 (1.03-1.67)) whereas the "protective" (B) haplotype was significantly less transmitted to IBD and CD patients. No interaction between CARD15 and TNFSF15 was detected. We also failed to define a clinical subgroup of CD patients specifically associated with TNFSF15 haplotype A. CONCLUSIONS: This study confirms that TNFSF15 or a closely linked gene is involved in the genetic predisposition to CD.

Genetic refinement and physical mapping of a chromosome 16q candidate region for inflammatory bowel disease.

Crohn's disease (CD) is a complex genetic disorder for which a susceptibility gene, IBD1, has been mapped within the pericentromeric region of chromosome 16. In order to refine the location of IBD1, 77 multiplex CD families were genotyped for 26 microsatellite markers evenly spaced by approximately 1 cM. Nonparametric linkage analyses exhibited a maximum NPL score of 3.49 (P=2.37x10(-4)) in a region centred by markers D16S3136, D16S3117 and D16S770. Simulation studies showed that the probability for IBD1 to be located in a 5 cM region around these markers was 70%. A 2.5 Mb YAC and BAC contig map spanning this genetic region on chromosome band 16q12 was built. TDT analyses demonstrated suggestive association between the 207 bp allele of D16S3136 (P<0.05) and a new biallellic marker hb27g11f-end (P=0.01). These markers were located in the hb27g11 and hb87b10 BAC clones from the contig. Taken together, the present results provide a crucial preliminary step before an exhaustive linkage disequilibrium mapping of putatively transcribed regions to identify IBD1.

Plasma levels of metrifonate and dichlorvos during treatment of schistosomiasis with bilarcil.

Metrifonate (0,0-dimethyl-[1-hydroxy-2,2,2-trichloroethyl]-phosphonate), and its rearrangement product dichlorvos (2,2-dichlorovinyl dimethyl phosphate) (DDVP), were studied in plasma from two patients with schistosomiasis who were treated with Bilarcil. A mass fragmentographic technique was used. Isotopic variants of the substances were used as internal standards and to compensate for DDVP formed during the workup procedure. The results were related to erythrocyte and plasmacholinesterase determinations. The method described makes it possible to study pharmacokinetics in man and to relate this information to therapeutic effects. It is proposed that metrifonate acts as a slow release formulation for DDVP.

Transanastomotic feeding tube after an operation for duodenal atresia.

UNLABELLED: The aim of this study was to answer the question whether or not, after an operation for duodenal atresia, a transanastomotic feeding tube reduces the time to full preanastomotic feeding. The method used was a retrospective study and a prospective observation. 18 consecutive newborns with duodenal atresia, nine from each of two different centres of paediatric surgery, were studied retrospectively. The patients in one centre received a nasogastric tube and a transanastomotic feeding tube during the operation, while in the other centre only a nasogastric tube was used. Seven control patients with duodenal atresia treated postoperatively with a nasogastric tube and a transanastomotic feeding tube were prospectively observed. The main outcome measure used to compare these two groups was the time required to achieve full preanastomotic feeding. RESULTS: The patients who were treated postoperatively with the transanastomotic feeding tube needed significantly less time to achieve full preanastomotic feeding than those with a nasogastric tube only (P < 0.001, Mann-Whitney U test). CONCLUSION: The use of a transanastomotic feeding tube, after an operation for duodenal atresia, leads to earlier full preanastomotic feeding.

Home parenteral nutrition (HPN) in children in Sweden.

This study represents a national survey of all children identified on home parenteral nutrition (HPN) in Sweden via all hospital pharmacy distributors. Indications for HPN from this sample were chronic intestinal pseudo obstruction (n = 5) and short bowel syndrome (n = 7). Linear growth was normal in 9 children and all school-age children attend classes at age-relevant levels. Families appear to have adapted well. There was one divorce among these families, and over the course of the HPN child's illness, younger siblings were born.

Frequency of epithelioid granulomas in colonoscopic biopsy specimens from paediatric and adult patients with Crohn's colitis.

AIMS: To test the assumption that epithelioid granulomas found in colonoscopic biopsy specimens in patients with Crohn's colitis are markers of a different clinical behaviour. METHODS: Sections from colonoscopic biopsy specimens from 352 consecutive patients (119 children and 233 adults) were investigated. RESULTS: A total of 1117 colonoscopies were performed: 293 in children (mean 2.46 per patient) and 824 in adults (mean 3.53 per patient) (p<0.05). Granulomas at initial colonoscopy were recorded in 67.2% (43/64) of children and 65.9% (27/41) of adults (p>0.6), and at subsequent colonoscopies in 53.8% (64/119) of children and 17.6% (41/233) of adults (p<0.05). Surgical intervention was required in 6.3% (4/64) of the children having previous granuloma, but also in 14.5% (8/55) of those without previous granuloma, the rate for operated adults being 26.8% (11/41) and 24.5% (47/192), respectively (p>0.6). CONCLUSIONS: Granulomas in entry and/or in subsequent colonoscopic biopsy specimens in patients with Crohn's colitis did not predict the need for subsequent surgical intervention. The fact that the frequency of granulomas was significantly higher in children than in adults with Crohn's colitis (despite a higher mean number of colonoscopic biopsies in adults), and that granulomas were present in colonoscopic biopsy specimens but not in the subsequent surgical specimens from 50% of the paediatric and 36% of the adult patients strengthen the conviction that granulomas in Crohn's colitis might evolve or regress at different time intervals during the course of the disease. This behaviour would reflect a particular immunological reaction, an epiphenomenon from immature tissues-as in children-when challenged by the so far elusive aetiological agent responsible for Crohn's disease.