[Capsule endoscopy in children: which are the best indications?]. / Quelles indications pour l'endoscopie du grêle par vidéocapsule en pédiatrie?

BACKGROUND AND STUDY AIMS: Capsule endoscopy (CE) is a novel and noninvasive means of investigating the small bowel. In children, the best CE indications have not yet been fully appraised. The aim of this study was to evaluate the diagnostic yield of CE in different pediatric pathologies. PATIENTS AND METHODS: We retrospectively reviewed every CE performed in children in two French pediatric hospitals between March 2002 and June 2009. Seventy-nine CEs were performed on 70 children (mean age, 10.6 years; range, 2.2-18.0); 52 boys and 18 girls. The indications were iron deficiency anemia (24%), obscure gastrointestinal bleeding (14%), polyposis syndromes (16%), suspected Crohn disease (15%), unresponsive Crohn disease (10%), graft-versus-host disease (10%), and other (10%). RESULTS: Of the 79 CEs, 69 reached the cecum (87%). Only one occlusion occurred in a case of stenosing Crohn disease, requiring surgical removal. In addition, technical difficulties led to an incomplete small bowel study in 12 cases (16%). The CE showed small bowel lesions in 42 cases (53%). The diagnostic yield was 27% in obscure gastrointestinal bleeding, 37% in iron-deficiency anemia, 42% in suspected Crohn disease, 88% in unresponsive Crohn disease, 62% in polyposis syndromes, and 88% in graft-versus-host disease. CONCLUSION: In children, CE is well tolerated and can be performed in children as young as 2.2 years of age. Its diagnostic yield is highest in polyposis syndromes, unresponsive Crohn disease, and graft-versus-host disease.

Treatments for pediatric achalasia: Heller myotomy or pneumatic dilatation?

AIM: The treatment of achalasia consists of reducing distal esophageal obstruction by either Heller myotomy surgery or endoscopic pneumatic dilatation. The aim of the present study was to evaluate the short- and middle-term results of these procedures in children. METHODOLOGY: For technical reasons, children under six years old (n=8) were treated by surgery only, whereas patients over six years old (n=14) were treated by either Heller myotomy or pneumatic dilatation. RESULTS: Of the children aged under six years, 75% were symptom-free at six months and 83% at 24 months of follow-up. Of the patients aged over six years, complete remission was achieved by Heller myotomy in 44.5% vs. 55.5% by pneumatic dilatation after six months, and in 40% vs. 65%, respectively, after 24 months. Both pneumatic dilatation and Heller myotomy showed significant rates of failure. CONCLUSION: These results suggest that pneumatic dilatation may be considered a primary treatment in children over six years old. Also, where necessary, Heller myotomy and pneumatic dilatation may be used as complementary treatments.

Prevention of relapse by mesalazine (Pentasa) in pediatric Crohn's disease: a multicenter, double-blind, randomized, placebo-controlled trial.

AIM: This study aimed to test the efficacy of mesalazine in maintaining remission in pediatric Crohn's disease (CD) following successful flare-up treatment. METHODS: In this double-blind, randomized, placebo-controlled trial, 122 patients received either mesalazine 50mg/kg per day (n=60) or placebo (n=62) for one year. Treatment allocation was stratified according to flare-up treatment (nutrition or medication alone). Recruitment was carried out over two periods, as the first period's results showed a trend favoring mesalazine. Relapse was defined as a Harvey-Bradshaw score more than or equal to 5. Time to relapse was analyzed using the Cox model. RESULTS: The one-year relapse rate was 57% (n=29) and 63% (n=35) in the mesalazine and placebo groups, respectively. We demonstrated a twofold lower relapse risk (P<0.02) in patients taking mesalazine in the medication stratum (first recruitment period), and a twofold higher risk in patients taking mesalazine in the nutrition stratum (second recruitment period), compared with the other groups. None of the children's characteristics, which differed across the two recruitment periods, accounted for the between-period variation in mesalazine efficacy. One serious adverse event was reported in each treatment group. CONCLUSION: Overall, mesalazine does not appear to be an effective maintenance treatment in pediatric CD.

Long-term outcome, growth and digestive function in children 2 to 18 years after intestinal transplantation.

OBJECTIVE: Small bowel (SB) transplantation (Tx), long considered a rescue therapy for patients with intestinal failure, is now a well recognised alternative treatment strategy to parental nutrition (PN). In this retrospective study, we analysed graft functions in 31 children after SBTx with a follow-up of 2-18 years (median 7 years). PATIENTS: Twelve children had isolated SBTx, 19 had combined liver-SBTx and 17 received an additional colon graft. Growth, nutritional markers, stool balance studies, endoscopy and graft histology were recorded every 2-3 years post-Tx. RESULTS: All children were weaned from PN after Tx and 26 children remained PN-free. Enteral nutrition was required for 14/31 (45%) patients at 2 years post-Tx. All children had high dietary energy intakes. The degree of steatorrhoea was fairly constant, with fat and energy absorption rates of 84-89%. Growth parameters revealed at transplantation a mean height Z-score of -1.17. After Tx, two-thirds of children had normal growth, whereas in one-third, Z-scores remained lower than -2, concomitant to a delayed puberty. Adult height was normal in 5/6. Endoscopy and histology analyses were normal in asymptomatic patients. Chronic rejection occurred only in non-compliant patients. Five intestinal grafts were removed 2.5-8 years post-Tx for acute or chronic rejection. CONCLUSIONS: This series indicates that long-term intestinal autonomy for up to 18 years is possible in the majority of patients after SBTx. Subnormal energy absorption and moderate steatorrhoea were often compensated for by hyperphagia, allowing normal growth and attainment of adult height. Long-term compliance is an important pre-requisite for long-term graft function.

Efficacy of methotrexate in pediatric Crohn's disease: a French multicenter study.

BACKGROUND: Immunosuppressors play a major role in maintaining remission in Crohn's disease (CD). In patients who do not tolerate or escape therapy with azathioprine (AZA)/6-mercaptopurine, there is a marked need for other immunosuppressive drugs. The aim of the present study was to evaluate the efficacy and safety of methotrexate (MTX) in children with active CD. METHODS: In a retrospective multicenter (n = 3) study, the efficacy of MTX to induce complete remission or a clinical improvement was analyzed in 61 children with active CD. RESULTS: CD was diagnosed at a mean age of 11.1 +/- 2.3 years, and MTX was introduced 3.1 +/- 2.2 years after diagnosis. Indications to use MTX were a nonresponse to or relapse under AZA (n = 42) or AZA intolerance/toxicity (n = 19). MTX improved or induced complete remission in 49 patients (80%), of whom 18 (29.5%) relapsed after 13 +/- 10 months of treatment. Under MTX medication, complete remission was observed in 39%, 49%, and 45% at 3, 6, and 12 months, respectively. Follow-up over at least 24 months in 11 children confirmed a sustained remission on MTX monotherapy up to 40 months. Adverse reactions were observed in 14 patients (24%), requiring discontinuation of MTX in 6 children (10%) (liver enzyme elevation, n = 2; varicella-zoster, n = 1; nausea, n = 3). MTX allowed corticosteroid discontinuation in 36 patients. CONCLUSIONS: MTX improved the clinical course in most pediatric CD patients who escaped or did not tolerate AZA. Short-time toxicity of MTX resulted in drug discontinuation in <10%. These data point to a beneficial and safe use of MTX in the treatment of pediatric CD.

Factors influencing outcome after intestinal transplantation in children.

We evaluated 131 patients (6 months-14 years) who experienced 21 deaths before listing, 11 continuing on the waiting list, 38 well on home parenteral nutrition, 6 off parenteral nutrition and 59 transplanted (20 girls) aged 2.5 to 15 years, (18 >7 years). They received cadaveric isolated intestine (ITx, n = 31) or liver-small bowel (LITx, n = 32), including right colon (n = 43; 23 LITx) for short bowel (n = 19), enteropathy (n = 20), Hirschsprung (n = 14), or pseudo-obstruction (n = 6). Treatment included tacrolimus, steroids, azathioprine, or interleukin-2 blockers. After 6 months to 10.5 years, the patient and graft survivals were 75% and 54%. Sixteen patients (10 LITx) died within 3 months from surgery (n = 3), bacterial (n = 5) or fungal (n = 6) sepsis, or posttransplant lymphoproliferative disorder (n = 2). Rejection occurred in 27 patients, including 10 steroid-resistant episodes requiring antilymphoglobulins. The grafts were removed due to uncontrolled rejection in seven ITx recipients. Surgical complications were observed in 38 recipients (25 LSBTx) within 2 months, including bacterial (n = 22) or fungal (n = 11) sepsis, cytomegalovirus disease (n=12), adenovirus (n = 11), or posttransplant lymphoproliferative disorder (n = 12). Forty-two children (19 LSBTx) are alive. Weaning from parenteral nutrition was achieved after 42 days (median). Factors related to death or graft loss were pre-Tx surgery (P < .01), pseudo-obstruction (P < .01), age over 7 years (P < .03), fungal sepsis (P < .03), steroid resistant rejection (P < .05), hospitalized versus home patient (P < .01), and retransplantation (P < .05). Colon transplant did not affect the outcome. Interleukin-2 blockers improved isolated ITx (P < .05). Early referral and close monitoring of intestinal failure and related disorders are mandatory to achieve successful ITx.

Reflux in esophageal atresia, tracheoesophageal cleft, and esophagocoloplasty: Bianchi's procedure as an alternative approach.

PURPOSE: Fundoplication has been used successfully to treat gastroesophageal reflux (GER) in the pediatric population. Although successful in many patients, there is a significant risk of complications and failure, especially in high-risk patients such as those with certain types of associated anomalies, diffuse motility disorders, chronic pulmonary disease, neurological impairment, and young infants. However, the results are poorer with children with severe pathologic lesion associated to reflux: tracheoesophageal cleft, esophagocoloplasty, and esophageal atresia (EA) with severe dysmotricity. In neurologically impaired children with neuromuscular incoordination and GER, Bianchi has proposed total esophagogastric dissociation (TED). The authors report the use of esophagogastric or esocologastric dissociation to control reflux in children with severe GER in other situations, such as EA, burn esophageal lesions having led to coloplasty and severe esotracheal cleft. METHODS: The authors reviewed the patients operated on for an esogastric or cologastric disconnection between 1997 and 2002. It is a single center retrospective study. The initial diagnosis, previous surgical procedure, postoperative course, and follow-up results were studied. RESULTS: Between September 1999 and June 2003, 13 TEDs were performed in 6 boys and 7 girls. The mean age for TED procedure was 35 months (range 14 days to 218 months). Indication for TED was severe persistent reflux in, respectively, 9 cases of EA (7 with coloplasty and 2 with preservation of the native esophagus after atresia repair, associated in 1 case with an esotracheal cleft), 2 cases of esotracheal cleft type III, and 2 cases of esophagocoloplasty for caustic burns. Six patients had undergone previous fundoplications (1-4 procedures) that failed, whereas the remaining patients underwent TED as the primary antireflux procedure. The average follow-up was 26 months (range 1 month to 4 years). There were no complication during the immediate postoperative course. Three children died at 3, 4, and 12 months after the procedure from acute respiratory failure. Respiratory status was improved in 8 children, and recurrent bronchitis was noted in 1 child. Regarding the digestive status, gastrostomy was closed at 18 and 24 months in 2 children, and partial nocturnal enteral nutrition (200 to 900 mL/d) through the gastrostomy remains necessary in the other children. CONCLUSION: Total esophagogastric dissociation procedure improves the respiratory consequences of severe GER, particularly in children for whom other surgical treatments have failed. The long-term safety of this operation remains to be determined especially regarding the consequences of a gastrointestinal Roux-en-Y loop procedure.

[Low bone mineral density in children with Crohn's disease]. / Déminéralisation osseuse au cours de la maladie de Chron de l'enfant.

UNLABELLED: Recent studies have reported low bone mineral density in children with Crohn's disease. The aims of this retrospective study were to quantify its frequency and to search for risk factors. POPULATION AND METHODS: Bone mineral density of 29 children with Crohn's disease was measured by dual-energy X-ray absorptiometry. All the children were taking calcium and vitamin D, during all the follow-up. RESULTS: Osteoporosis (Z-score < or = -2.5 S.D.) was found in 38% of the children, and osteopenia in 38% (Z-score between -1 and -2.5 S.D.). Low bone mineral density was correlated with age, suggesting it begins with puberty. Daily corticosteroid exposure was significantly higher for patients with osteoporosis. Disease severity measured with Harvey-Bradshaw index and exposure to immunosuppressive drugs were almost statistically significant. Sex, height, duration and site of disease, nutritional assistance exposure were not associated with low bone mineral density. CONCLUSION: This study confirms the high frequency of low bone mineral density in children with Crohn's disease, mainly during puberty. Corticosteroid exposure is a risk factor, and the disease severity, a probable one (non significant). New treatment strategy has to be defined to prevent and to treat this complication.

[Failure to thrive and intestinal diseases in congenital disorders of glycosylation]. / Hypotrophie et manifestations digestives des désordres congénitaux de la glycosylation.

UNLABELLED: Congenital disorders of glycosylation type I (GDG-I) is a class of genetic multisystem disorders characterised by defective glycosylation of glycoproteins. The characteristics and mechanisms of failure to thrive and intestinal diseases present in CDG-I are anectodal. PATIENTS AND METHODS: The aim of this study was to analyse 7 CDG-I (4 CDG-Ia, 2 CDG-Ib and 1 CDG-Ix) with important digestive symptoms and failure to thrive in order to characterise the mechanisms implied. RESULTS: Four children had no skin abnormality or dysmorphia (1 CDG-Ia, 2 CDG-Ib, 1 CDG-Ix). An encephalopathy with cerebellar hypoplasia was present only in the 4 CDG-Ia. Failure to thrive and diarrhea were present during the first month of life in 6 and appeared at 5 years in one CDG-Ia associated to mild or severe hepatopathy in all patients. One CDG-Ia, 1 CDG-Ib, 1 CDG-Ix had an exsudative enteropathy. A positive steatorrhea was present in 3 patients. Five patients had an abnormal small bowel biopsy. Abnormalities were variable: moderate inflammation of the chorion without villous atrophy in 2, intra-enterocyte fat accumulation without villous atrophy in 2, and partial villous atrophy with lymphangectasia in 1. In 2 CDG-Ia the intestinal biopsy was normal. Enteral nutrition in 4 and parenteral nutrition in 2 were effective in 4 patients and 1 patient with an exsudative enteropathy respond to a free fat diet (CDG-Ix). CONCLUSION: The digestive symptoms with failure to thrive is a common feature of CDG-I and could be the first symptoms. The diagnostic should be suspected if no other cause is found. Mechanisms of the intestinal symptoms appear to be multiple such as inflammation, abnormal enterocyte lipid transport or intestinal permeability related to the abnormal glycosylation of intestinal mucosa glycoproteins.

Card15 gene overexpression in mononuclear and epithelial cells of the inflamed Crohn's disease colon.

BACKGROUND: Crohn's disease is one of the principal human chronic inflammatory bowel diseases. Although its aetiology is still unknown, its complex pathogenesis has environmental, immunological, and genetic determinants. CARD15 is the first susceptibility gene implicated in the predisposition to Crohn's disease and is known to be expressed only in monocytes. However, its expression in situ has not yet been studied. AIMS: To analyse the tissue distribution of CARD15 and identify cells producing CARD15 in samples of colon from patients with Crohn's disease and control subjects. PATIENTS AND METHODS: We analysed CARD15 gene expression in surgical specimens of colon from eight children with Crohn's disease and nine controls by immunohistochemistry, in situ hybridisation, and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: We showed that CARD15 was present only in the cytoplasm of macrophages in the normal colon. Increased CARD15 expression was detected in Crohn's disease lesions. There were more CARD15 positive cells in Crohn's disease lesions than in uninvolved areas. Both intestinal epithelial cells, macrophages, and their derivatives overproduced CARD15 in Crohn's disease. To further assess CARD15 expression by intestinal epithelial cells, we performed RT-PCR on freshly isolated intestinal epithelial cells, and showed that these cells isolated from Crohn's disease samples contained more CARD15 mRNA than intestinal epithelial cells from controls. CONCLUSIONS: We have demonstrated that colonic involvement in active Crohn's disease is associated with increased CARD15 gene expression in both macrophages and intestinal epithelial cells. Therefore, this deregulation can affect the host-environment interaction and thus contribute to the pathogenesis of this disease.

CARD4/NOD1 is not involved in inflammatory bowel disease.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex genetic disorders. CARD15/NOD2, a member of the Ced4 superfamily which includes Apaf-1 and CARD4/NOD1, has recently been associated with genetic predisposition to CD but additional genetic factors remain to be identified. Because CARD4/NOD1 shares many structural and functional similarities with CARD15, we tested its putative role in IBD. PATIENTS AND METHODS: The 11 exons of CARD4 were screened for the presence of variants in 63 unrelated IBD patients. The only non-private genetic variation encoding for a substitution in the peptidic chain was genotyped in 381 IBD families (235 CD, 58 UC, 81 mixed, and seven indeterminate colitis families) using a polymerase chain reaction-restriction fragment length polymorphism procedure. Genotyping data were analysed by the transmission disequilibrium test. RESULTS: Five of nine sequence variations identified in the coding sequence of the gene encoded for non-conservative changes (E266K, D372N, R705Q, T787M, and T787K). Four were present in only one family. The remaining variant (E266K), which exhibited an allele frequency of 0.28, was not associated with CD, UC, or IBD. Furthermore, IBD patients carrying sequence variations in their CARD4 gene had a similar phenotype to those with a normal sequence. CONCLUSION: Our results suggest that CARD4 does not play a major role in genetic susceptibility to IBD.

Growth in paediatric Crohn's disease.

Growth failure (GF) is one of the major complications affecting children with inflammatory bowel disease. The faltering is temporary in 40-50% of cases and prolonged in 10-20% in Crohn's disease (CD). Such failure is rare in children with ulcerative colitis (5%). This complication is often associated with retarded bone development and delayed onset of sexual maturation. The delayed linear growth has a variety of causes including insufficient intake due to anorexia and the inflammatory process with increased energy and protein expenditure. Other factors are increased intestinal loss, secondary hypopituitarism and treatment with steroids. Therapeutic strategies of CD in children have changed this last decade by introducing new therapeutic agents such as topic steroids, immunosuppressors, anti-TNF (antibody and notably in children enteral nutrition which has shown its efficacy in inducing remissions of active CD, restoring nutritional status and stimulation of linear growth. The results of a recent prospective multicentric study over 2 years in 82 CD show that severe GF (-2 SD) is initially present in 15% (n = 12), among them 11 remain < -2SD after 2 years of follow-up. Six patients who were on the normal range initially increased their GF during the follow-up (< -2SD) (total 21% < -2SD (n = 17) at 2 years). At inclusion in this group there was no difference in growth velocity, used of steroids, enteral nutrition or severity of CD as compared to the group with no GF. It suggests that new treatment strategy should be developed in the future for this specific complication of paediatric CD.

[Pancreatic involvement in inflammatory bowel diseases in children]. / Atteintes pancréatiques dans les maladies inflammatoires du tube digestif de l'enfant.

UNLABELLED: Pancreatitis in inflammatory bowel disease (IBD) in children is anecdotal. In adults, symptomatic pancreatitis occurs in 2% and asymptomatic in 8 to 21%. PATIENTS AND METHODS: The aim of our study was to review retrospectively the frequency of pancreatitis in 124 pediatric patients (54.8% boys, 45.2% girls; 97 with Crohn disease, 16 with ulcerative colitis and 11 with undetermined colitis). Diagnostic criterion of pancreatitis was an increase of amylasemia > or = +2 SD of the normal with or without evocative clinical symptoms. RESULTS: Symptomatic or asymptomatic pancreatitis was found in 27% (respectively 14.5 and 12.5%). Pancreatitis was significantly more frequent in girls as compared to boys (P = 0.04). Symptomatic pancreatitis was moderate and non complicated, often recurrent. It occurred mainly during active and severe diseases (P = 0.006). The localizations of IBD were not discriminant. Strong relation with drug was found in 25% of pancreatitis mainly due to azathioprine or 5-aminosalicylic acid, and salazopyrin. Duodenal localisation of Crohn disease or hepatobiliary complications were found associated with pancreatitis in 18% and 15% respectively. CONCLUSION: These data suggest the high incidence of symptomatic and asymptomatic pancreatitis in children with IBD, the importance of its regular monitoring but also its multifactorial causes. Precise diagnosis of pancreatitis in pediatric IBD has to be done in order to avoid inappropriate drug pancreatitis diagnosis.

Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.

Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-kB; this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.

[Nutritional status and risk in hospitalized children]. / Etat et risque nutritionnel de l'enfant hospitalisé.

BACKGROUND: A few studies report malnutrition in hospitalized patients. MATERIAL AND METHODS: This one-day cross-sectional survey performed in January 1999 assessed nutritional status and protein-energy intake in a pediatric population hospitalized in medicine or surgery units. Every child older than six months, hospitalized for more than 48 h and free of nutritional support (parenteral, enteral, or special regimens for metabolic diseases) was included. RESULTS: Fifty-eight children among the 183 present the day of the study met the inclusion criteria and were included in the statistical analysis. They were hospitalized in medicine (48%), psychiatry (31%) and surgery (21%). The body mass index (BMI) was below -2 standard deviations (DS) in 21% of them. Excluding patients with anorexia nervosa, BMI was < -2 SD, > +2 SD, or in between these limits in respectively 12, 14 and 74%. Energy intake measured at the hospital was below 75% of the recommended dietary allowances in two-thirds of the children whether malnourished or not. Fifty percent of the malnourished children had been referred to a dietician the day of the study. CONCLUSIONS: Malnutrition is frequent in a population of hospitalized children. Energy intake and referral to a dietician are insufficient.

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.

[Pediatric gastrointestinal endoscopy: which sedation?]. / Endoscopie digestive pédiatrique: quelle sédation?

Through an analysis of the French experience of digestive endoscopists in adult patients and of their own 25 years practice of pediatric digestive endoscopy, the authors militate in favour of anesthetic sedation in order to reduce painfulness and to obtain better acceptation of these procedures by children and their parents.

Genetic analyses of chromosome 12 loci in Crohn's disease.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease, both of which are multifactorial diseases involving the interaction of genetic and environmental factors. A region on chromosome 12 centred around the marker locus D12S83 has previously been associated with IBD predisposition. The aim of the study was to investigate this genetic region in an independent panel of European families affected by Crohn's disease. METHODS: A sample of 95 families with two or more affected relatives and 75 simplex nuclear families were genotyped for 19 microsatellite loci located on chromosome 12. A search for linkage and linkage disequilibrium was performed using non-parametric two point and multipoint analyses with the Analyze and Genehunter packages. RESULTS: No evidence of linkage or linkage disequilibrium was observed for any of the marker loci, including D12S83 (p=0.35 for the two point linkage test). Multipoint linkage analysis also failed to reveal positive linkage on chromosome 12. Power calculations allowed us to reject the hypothesis that the genetic region of chromosome 12 centred on D12S83 contains a susceptibility locus with a relative risk (lambda(s)) equal to or greater than 2.0 in these families. CONCLUSION: Failure to detect linkage or linkage disequilibrium in these families suggests that the chromosome 12 locus previously reported to be associated with genetic predisposition to IBD does not play a role in all European family samples. This observation is compatible with heterogeneity in the genetic basis of susceptibility to the disease and/or exposure to various environmental factors among Caucasian families.

Effects of oral Saccharomyces boulardii on bacterial overgrowth, translocation, and intestinal adaptation after small-bowel resection in rats.

BACKGROUND: Small-bowel resection in animals results in alterations of the morphology and functional adaptation in the remaining intestine. The aim of our study was to study the effect of Saccharomyces boulardii versus placebo in rats after 50% small-bowel resection. METHODS: Sixty-three rats were assigned to one of three groups: small-bowel resection (n = 31), transected surgery controls (n = 16), or non-surgical controls (n = 16). Of the 31 rats with small-bowel resection, 15 were given S. boulardii (140 mg/dl), and 16 were given placebo. Intestinal markers measured included bacterial overgrowth (BO) on days 4 and 8 and translocation into mesenteric lymph nodes, liver, and spleen. Markers of small-bowel adaptation included histomorphology of the mucosa, protein content, and various brush-border enzymes (sucrase, glucoamylase, n-aminopeptidase). RESULTS: In the jejunal mucosal samples on day 8, S. boulardii-treated rats showed a significant increase in protein content (58.3 +/- 12 mg/10 cm) compared with placebo-treated rats (29.2 +/- 1.8) or non-surgery controls (18.3 +/- 1.2; P < 0.001). S. boulardii-treated rats also had significantly higher levels of all three brush-border enzymes. A significant increase of enzyme-specific activities was observed in the ileum of S. boulardii resected rats compared with the placebo resected group on day 4, and no significant differences were seen in the remnant ileum except an increase in protein content in S. boulardii-treated rats on day 8. Histomorphometric studies showed no differences in ileal villus height or translocation frequencies by day 8 in S. boulardii or placebo resected rats. CONCLUSIONS: These data indicate that, after resection, S. boulardii does not modify bacterial overgrowth or translocation frequency but does significantly enhance the functional adaptation of the remaining intestinal segments.