[Nocturnal gastroesophageal reflux. About a pH metric series]. / Le reflux gastro-oesophagien acide nocturne pathologique. A propos d'une série pHmétrique.

BACKGROUND: Nocturnal gastroesophageal reflux has been shown to be associated with the more severe forms of gastroesophageal reflux disease (GERD), particularly with extraesophageal manifestations as well as complications of mucosal damage. AIM: To determine the frequency of nocturnal gastro esophageal reflux disease on 24-hour esophageal pH monitoring in patients with digestives or extra-digestives symptoms and to evaluate the clinical and pHmetric characteristics of nocturnal reflux in these patients. METHODS: We conducted a retrospective study based on results of 24- hour esophageal pH monitoring during a 11-year period in patients with or without digestive symptoms of gastroesophageal reflux disease. The nocturnal gastroesophgeal reflux was defined. RESULTS: We studied 696 patients (299 men, 397 women; mean age: 34.05 years). Gastroesophageal reflux was found in 350 patients (50%). Nocturnal reflux was observed in 240 patients (34.3%), mostly in association with pathological reflux in the total period (223 cases). Compared to the diurnal period, the nocturnal period was characterized by fewer number of reflux episodes (21.9±27.4 vs 67.4±5.,1 ; p<0.0001), more longer duration of reflux episodes (24.4±37.9 minutes vs 13.9± 17.5 minutes ; p<0.001), and a lower symptomatic correlation (26% vs 45% ; p=0.0005). CONCLUSION: Nocturnal reflux is associated with overall reflux on the 24 hour examination. Nocturnal period is characterized by longer reflux episodes, less number of reflux episodes and less symptomatic correlation.

[Epithelial cell in intestinal homeostasis and inflammatory bowel diseases]. / Rôle de la cellule épithéliale dans l'homéostasie intestinale et les maladies inflammatoires chroniques de l'intestin.

Crohn's disease (CD) and ulcerative colitis (UC) are the principal inflammatory bowel diseases (IBD) which physiopathology is currently poorly elucidated. During these diseases, the participation of the epithelial cell in the installation and the perpetuation of the intestinal inflammation is now clearly implicated. In fact, the intestinal epithelium located at the interface between the internal environment and the intestinal luminal, is key to the homeostatic regulation of the intestinal barrier. This barrier can schematically be regarded as being three barriers in one: a physical, chemical and immune barrier. The barrier function of epithelial cell can be altered by various mechanisms as occurs in IBD. The goal of this article is to review the literature on the role of the epithelial cell in intestinal homeostasis and its implication in the IBD.

[Evaluation of small bowel involvement in Crohn's disease by small- bowel videocapsule endoscopy: a prospective comparative study with computed-tomography enteroclysis and small bowel radiography]. / Évaluation de l'atteinte du grêle de la maladie de Crohn par vidéocapsule endoscopique : étude prospective et comparative avec le transit du grêle et l'entéroscanner.

BACKGROUND: Small-bowel videocapsule endoscopy (VCE) is a new technique in evaluation of intestinal involvement in several pathologies. Crohn's disease affects principally terminal ileum. Small bowel involvement in Crohn's disease is not well estimated by endoscopic and radiologic conventional techniques. AIMS: To evaluate the performances of VCE in detection of asymptomatic proximal small bowel lesions in consecutive patients with Crohn's disease with terminal ileal involvement, to compare the results of VCE to small bowel radiography and CT-enteroclysis and to determine the therapeutic impact of VCE in these patients. METHODS: A prospective study which included Crohn's disease patients with distal ileal involvement, based on radiological or endoscopic findings. We performed in all patients small bowel radiography, CT enteroclysis and VCE. Proximal involvement was characterized by presence of aphtoid, superficial or deep ulcerations in the jejunum or the proximal ileum. RESULTS: We studied 20 patients (12 men, mean age 31.6 years). VCE confirmed the distal ileal involvement in all patients. Significative proximal lesions was observed in nine patients (jejunum only: one case, jejunum and ileum: six cases and proximal ileum: two cases), in most cases aphtoid or superficial lesions. Deep ulcerations were observed in two patients. Small bowel radiography showed proximal ileal lesions in only two patients, and CT-enteroclysis in only one patient. Treatment by azathioprine was prescribed in two patients with severe and extended small bowel lesions in VCE examination. CONCLUSION: VCE is more accurate than radiologic techniques in detection of small bowel lesions in Crohn's disease. In cases of severe and extended small bowel involvement, VCE can conduct to changes of therapeutic approach.

[Fertility and inflammatory bowel diseases]. / Fertilité et maladies inflammatoires chroniques de l'intestin.

BACKGROUND: Data concerning fertility during inflammatory bowel disease are insufficient and sometimes contradictory. The aims of this review are to precise the impact of inflammatory bowel disease on fertility. METHODS: Literature review. RESULTS: The risk of infertility seems to be raised at one under group of patients and made to intervene several factors of which, in particular for the Crohn's disease, the activity of the disease and the psychological impact leads by this chronic disorder. The decrease of the fertility, as very feminine as male, during the ulcerative colitis is essentially bound to the surgery. Data concerning the impact of various therapeutic used during inflammatory bowel disease on the fertility are very insufficient and interest especially male fertility.

Primary resistance to clarithromycin, metronidazole and amoxicillin of Helicobacter pylori isolated from Tunisian patients with peptic ulcers and gastritis: a prospective multicentre study.

BACKGROUND: The frequency of primary resistance to antibiotics in H. pylori isolates is increasing worldwide. In Tunisia, there are limited data regarding the pattern of H. pylori antibiotic primary resistance. AIM: To evaluate the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and to detect the mutations involved in clarithromycin resistance. MATERIALS AND METHODS: 273 strains isolated from adults and children were enrolled. The primary resistance to clarithromycin, metronidazole and amoxicillin was evaluated by means of E-test minimal inhibitory concentration (MIC). The real-time PCR using Scorpion primers was performed in all cases to assess clarithromycin primary resistance and point mutations involved. RESULTS: No resistance to amoxicillin was detected. For adults, resistance to clarithromycin and metronidazole was found respectively in 14.6% and 56.8%, and respectively in 18.8% and 25% in children. Overall, the rates of global primary resistance to clarithromycin and metronidazole in Tunisia were respectively determined in 15.4% and 51.3%.By the use of Scorpion PCR, the A2143G was the most frequent point mutation observed (88.1%), followed by the A2142G (11.9%); the A2142C was not found and 18 of 42 patients (42.8%) were infected by both the resistant and the susceptible genotype.The association of clarithromycin resistance with gender was not statistically significant, but metronidazole resistant strains were isolated more frequently in females (67.8%) than in males (32.2%) and the difference was significant. As for gastroduodenal diseases, the difference between strains isolated from patients with peptic ulceration and those with non peptic ulceration was not statistically significant. When about the distribution of resistant strains to clarithromycin and metronidazole between the three Tunisian cities (Tunis, Menzel Bourguiba and Mahdia), the difference was not statistically significant. CONCLUSION: Local data regarding the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and the main genetic mutation involved in clarithromycin resistance in vivo (A2143G) are necessary to prove a clear need for a periodic evaluation of antibiotic consumption and new therapeutic strategies in Tunisia in order to avoid the emergence of resistant strains.

[Sleep disorders in patients with gastroesophageal reflux disease: an open clinical and pH metric prospective study]. / Perturbations du sommeil au cours du reflux gastro-oesophagien: Résultats d'une etude prospective ouverte clinique et Ph-métrique.

BACKGROUND: Sleep disorders are frequent in patients with GERD. Severity of sleep disorders could be related to occurrence of nighttime symptoms, but the relationship between severity of GERD and the severity of sleep disorders is not well established. AIM: To identify the frequency of sleep disorders in patients with suspected GERD and the correlation between the severity of sleep disorders and pHmetric parameters in these patients. METHODS: We studied prospectively 50 patients with esophageal and supra-esophageal symptoms of GERD. 24-hour esophageal pH monitoring examination was performed in all patients. Standard survey was applied to determine the frequency and the severity of sleep disorders in these patients. RESULTS: We included 50 patients (10 men, 40 women), mean age 43.7 years (18-70). Nighttime symptoms were present in 26 patients (52%). Pathological acid gastro-esophageal reflux was diagnosed by 24-hour esophageal pH recording in 18 patients (36%), with nocturnal acid reflux in 19 patients (38%). Sleep disorders were reported by 29 patients (58%). Mean number of hours of sleep was 6.8 hours by night (4-9 hours). Clinical factors associated with higher frequency of sleep disorders were occurrence of nighttime symptoms (p < 0.0001) and duration of symptoms of GERD (53.2 +/- 41.4 months vs 26.0 +/- 18.1 months ; p = 0.007), with no association with BMI, age and sex. pHmetric parameters associated with sleep disorders were pathological acid reflux (p < 0.0001; OR [CI 95%]: 28.3 [3.3-240.8]) and nocturnal acid reflux (p < 0.0001; OR[CI95%] :32.7 [3.8 - 279.2]). Patients with sleep disorders had significant changes of pHmetric parameters compared to those without sleep disorders: Acid exposition time, numbers of reflux episodes, number of episodes longest than five minutes, duration of longest reflux episode and DeMeester score (respectively 6.1 +/- 8.8 vs 1.3 +/- 1.5 p = 0.01; 59.2 +/- 52.0 vs 20.7 +/- 21.6 p = 0.001; 3.1 +/- 6.1 vs 0.1 +/- 0.3 p = 0.03; 8.9 +/- 9.3 minutes vs 3.4 +/- 4.0 minutes p = 0.01; 24.0 +/- 33.2 vs 4.8 +/- 4.9 p = 0.01). Number of hours of sleep was significantly lower in patients with pathological acid reflux (5.3 +/- 1.2 hours vs 7.6 +/- 1.7 hours, p < 0.0001) and in patients with nocturnal acid reflux (5.2 +/- 1.1 hours vs 7.8 +/- 1.5 hours, p < 0.0001). Number of hours of sleep was strongly correlated with esophageal pH parameters CONCLUSION: Sleep disorders are frequent in patients with GERD symptoms. Severity of sleep disorders are strongly correlated with severity of global and nocturnal acid reflux as attested by 24-hour esophageal pH monitoring.

Fecal calprotectin is a predictive marker of relapse in Crohn's disease involving the colon: a prospective study.

OBJECTIVES: Fecal calprotectin seems to have a diagnostic precision in predicting relapse in quiescent ulcerative colitis patients. However, the data remain controversial in Crohn's disease. The aim of this study was to prospectively evaluate the role of fecal calprotectin as a predictive marker for 1-year follow-up in patients with asymptomatic Crohn's disease. METHODS: Fifty-three Crohn's disease patients in clinical remission were consecutively included providing at the beginning of the study a single stool sample as well as a blood sample and regularly followed-up for 12 months. Fecal calprotectin level was measured using a commercially available enzyme-linked immunoassay. RESULTS: Among 53 patients, 10 (18.9%) developed clinical relapse during the 12-month follow-up period. Median fecal calprotectin level was significantly higher in relapse group patients compared with that in nonrelapse group (380.5 vs. 155 microg/g, P<0.001). With a cutoff value of 340 microg/g fecal calprotectin gave sensitivity of 80% and specificity of 90.7% in predicting clinical relapse. Fecal calprotectin level greater that 340 microg/g gave an 18-fold higher risk to develop relapse (log rank P<0.001) and was found to be an independent predictive factor of relapse (P=0.02). CONCLUSION: Fecal calprotectin seems to be a reliable marker of relapse in quiescent Crohn's disease patients.

Frequency and predictive factors of granulomatous hepatitis in patients with peritoneal tuberculosis.

AIMS: The aims of our study were to determine the frequency of granulomatous hepatitis in patients with peritoneal tuberculosis, to identify factors for high risk and whether it is associated with higher frequency of antituberculous treatment side effects. METHODS: We carried out a prospective study on patients with histologically proven peritoneal tuberculosis between January 1996 and December 2005. We performed a liver biopsy in all the patients before starting the antituberculous treatment. Granulomatous hepatitis was systematically searched in all patients. RESULTS: The study was conducted in 52 patients, 9 men and 43 women of median age of 35,5 years. A granulomatous hepatitis was seen in 24 patients (46%). In univariate analysis the factors associated with a high risk of liver involvement were a higher level of gamma-glutamyl transpeptidase (44.5 + 36.8 IU/l vs 23.3 + 9.28 IU/l p = 0.005), a higher level of phosphatases alkalines (233.9 + 96.6 IU/l vs 189.4 + 49.9 IU/l p = 0.03) and a lower level of cholesterol (1.22 + 0.2 g/l vs 156 + 0.3 g/l p < 0.0001). In multivariate analysis, only a cholesterol level lower than 1,31 g/l was significantly associated with a granulomatous hepatitis (p = 0.006 OR [IC 95%]: 0.10 [0.02-052]). CONCLUSION: We have found a frequent liver involvement in the case of peritoneal tuberculosis (46%). Cholesterol level lower than 1,31 gr/l was an independent predictor of granulomatous hepatitis in patients with peritoneal tuberculosis. We suggest, in this case, that percutaneous liver biopsy can be considered as an alternative to laparoscopy.

Tolllike receptor 4 (TLR4) polymorphisms in Tunisian patients with Crohn's disease: genotype-phenotype correlation.

BACKGROUND: The immune responses to bacterial products through the pattern recognition receptor (PRR) play a pivotal role in pathogenesis of Crohn's disease. A recent study described an association between CD and some gene coding for bacterial receptor like NOD2/CARD15 gene and TLR4. In this study, we sought to determine whether TLR4 gene was associated with Crohn's disease (CD) among the Tunisian population and its correlation with clinical manifestation of the disease. METHODS: 90 patients with CD and 80 healthy individuals are genotyped for the Asp299Gly and Thr399Ile polymorphisms by restriction fragment length polymorphism analysis. RESULTS: The allele and genotype frequency of the TLR4 polymorphisms did not differ between patients and controls. The genotype-phenotype correlation permitted to show that the Thr399Ile polymorphism was associated with early onset disease. CONCLUSION: this study reported the absence of association between CD and TLR4 gene in the Tunisian population, but this gene could play a role in clinical expression of the disease.

Association of Fas/Apo1 gene promoter (-670 A/G) polymorphism in Tunisian patients with IBD.

AIM: To detect a possible association between the polymorphism of the (-670 A/G) Fas/Apo1 gene promoter and susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) in the Tunisian population. METHODS: The (-670 A/G) Fas polymorphism was analyzed in 105 patients with CD, 59 patients with UC, and 100 controls using the polymerase chain reaction restriction fragment length polymorphism method. RESULTS: Significantly lower frequencies of the Fas -670 A allele and A/A homozygous individuals were observed in CD and UC patients when compared with controls. Analysis of (-670 A/G) Fas polymorphism with respect to sex in CD and UC showed a significant difference in A/A genotypes between female patients and controls (P corrected = 0.004 in CD patients and P corrected = 0.02 in UC patients, respectively). Analysis also showed a statistically significant association between genotype AA of the (-670 A/G) polymorphism and the ileum localization of the lesions (P corrected = 0.048) and between genotype GG and the colon localization (P corrected = 0.009). The analysis of inflammatory bowel disease patients according to clinical behavior revealed no difference. CONCLUSION: Fas-670 polymorphism was associated with the development of CD and UC in the Tunisian population.

Association between CTLA-4 gene promoter (49 A/G) in exon 1 polymorphisms and inflammatory bowel disease in the Tunisian population.

BACKGROUND/AIM: To investigate the possible association between the polymorphism of the CTLA-4 exon 1 +49 A/G and susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) in the Tunisian population. METHODS: The +49 A/G dimorphism was analyzed in 119 patients with CD, 65 patients with UC, and 100 controls by the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: Significantly higher frequencies of the CTLA-4 +49A allele and A/A homozygous individuals were observed in patients with CD when compared with controls (pc = 0.0023 and pc = 0.0003, respectively). Analysis of CTLA-4 A/G polymorphism with respect to sex in CD showed a significant difference in A/A genotypes between female patients and controls (pc = 0.0001 and pc = 0.038, respectively). There were no differences in the subgroups of patients with CD. CONCLUSIONS: Forty-nine A alleles and AA genotype are associated with CD susceptibility in Tunisians. Other genes involved in the T-cell regulation remain strong candidates for IBD susceptibility and require further investigation.

[Frequency and predictive factors of colectomy and restorative colo-proctectomy in ulcerative colitis]. / Frequence et facteurs predictifs de colectomie et de coloproctectomie au cours de la rectocolite hemorragique.

AIMS: To determine the frequency and the predictive factors of colectomy and restorative colo-proctectomy in patients with ulcerative colitis. METHODS: We conducted an 11-year retrospective study based on hospitalized ulcerative colitis patients followed up for more than 6 months. RESULTS: From 1995 to 2005, 115 patients were included (50 men, 65 women, mean age: 38.4 years). Mean duration of follow-up was 39.2 months (6 - 145). Colectomy was performed in 20 patients (17%), with an actuarial risk of 16% at 5 years and 35% at 10 years. Proctocolectomy with ileoanal anastomosis was performed in 16 cases and total colectomy with ileorectal anastomosis in 4 cases. In univariate analysis, factors associated with an increased risk of colectomy were pancolitic location (p = 02), acute severe colitis (p < 0.0001), treatment by intravenous corticosteroids (p < 0.0001) and intravenous cyclosporine (p = 0.001). In multivariate analysis, acute severe colitis was the only independent factor associated with colectomy (p = 0.04 OR [CI 95%] :6.66 [1.04 - 50]). In patients with distal location, the independent factor associated with colectomy was colonic extension during follow up (p = 0.04 OR [CI 95%] :7.69 [1.07 - 50]). In patients with pancolitic location, risk of colectomy was associated with acute severe colitis (p = 0.01 OR [CI 95%] :9.09 [1.58 - 50]) and years of hospitalization from 1995 to 1999 (p = 0.02 OR [CI 95%] :7.14 [1.35 - 44]). CONCLUSION: Although the diffusion of treatment by intravenous cyclosporin, surgery is frequently performed in our ulcerative colitis patients, specially in case of acute severe colitis. Evaluation of colonic extension during the follow-up is associated with an important prognostic impact.

Polymorphism in ICAM-1, PECAM-1, E-selectin, and L-selectin genes in Tunisian patients with inflammatory bowel disease.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are chronic intestinal disorders characterized by immune dysregulation and leukocytes recruitment into gastrointestinal tract. Cell adhesion molecules (CAM) mediate the extravasation of leukocytes and their accumulation in inflamed intestinal mucosa. Recently, CAM genes have been implicated in determining susceptibility to UC and CD. We investigate seven mutations in CAM: G241R and K469E in ICAM-1, V125L in PECAM-1, G98T, S128R, and L554F in E-selectin and F206L in L-selectin in 197 Tunisian patients (73 with UC and 124 with CD) and 194 controls. These polymorphisms were detected by polymerase chain reaction sequence-specific primers and restriction enzyme analysis. RESULTS: A significant increase in allele frequencies of 206L of L-selectin and the associated genotype F/L was observed in both patients with UC and CD compared with controls. Subgroup analysis showed that the L206 allele and F/L206 genotype frequencies were significantly increased in UC patients with left-sided type; whereas, the F/L206 genotype was significant in CD patients with ileocolonic location and stricturing behavior compared with controls. No significant differences in allele or genotype frequencies were observed for ICAM-1 K469E, E-selectin, and PECAM-1 polymorphisms between UC patients, CD patients, and controls. CONCLUSION: We found an association of inflammatory bowel disease with allele L206 of L-selectin gene, whereas genotype L/F was associated with a subgroup of UC (left-sided type) and CD patients with more extensive location of disease and stricturing behavior. However, further studies are needed to confirm our findings.

[Treatment of Crohn's disease by infliximab. About 20 cases]. / Traitement de la maladie de Crohn par infliximab: a propos de 20 cas.

BACKGROUND: Infliximab has been an effective chimerical monoclonal antibody in Crohn's disease. Infliximab is available in Tunisia for a few years. AIMS: To determine the results of the treatment of Crohn's disease by infliximab. METHODS: We undertook a retrospective study relating to all the Crohn's disease patients and treated by infliximab. For all the patients, we specified the indication of the treatment, the result of the induction treatment, the recourse or not to a sequential treatment and the adverse effects of the treatment. RESULTS: Our study related to 20 patients. It was in the majority of the cases an anoperineal and fistulizing form (15 case). Good response to the induction treatment was noted in 15 patients (75%). A sequential treatment by infliximab was undertaken among seven patients, with good results in the short and medium term. A case of death related to the treatment was noted in our series, as mortal milliary tuberculosis appeared under treatment. CONCLUSION: Infliximab must be reserved for particular situations of the Crohn's disease. The pre-therapeutic assessment must be complete and the monitoring of the patients must be strict, while insisting on the possibility of reactivation of latent tuberculosis in Tunisia.