Prognostic factors in Crohn's disease: a systematic review.

BACKGROUND: The natural history of Crohn's disease is associated with several factors that affect the prognostic of the patients. AIMS: To determine the most prognostic factors in Crohn's disease, based on a systematic review. METHODS: Literature review. RESULTS: The most important factors to consider in patients with Crohn's disease are the need for immunosuppressive therapy, the need for intestinal resection and disabling disease. Prognostic factors for these events are ileal involvement, perianal disease and initial treatment by corticosteroid. Other factors such young age, CRP level and smoking status, has not been found in all population-based studies. Protective role of anti-TNF drugs is strongly suggested but need to be confirmed in further studies. CONCLUSION: In a selected subgroup of patients with Crohn's disease characterized by the presence of these prognostic markers, the "topdown" strategy can be proposed.

Circulating antimyenteric autoantibodies in Tunisian patients with idiopathic achalasia.

The physiopathology of idiopathic achalasia is still unknown. The description of circulating antimyenteric autoantibodies (CAA), directed against enteric neurons in sera of patients, suggests an autoimmune process. Recent data showed controversies according to the existence and the significance of CAA. The aims of this study were to investigate whether CAA are detected in Tunisian patients with idiopathic achalasia and to look for associated clinical or manometrical factors with CAA positivity. Twenty-seven patients with idiopathic achalasia and 57 healthy controls were prospectively studied. CAA were assessed by indirect immunofluorescence on intestinal monkey tissue sections. Western blot on primate cerebellum protein extract and dot technique with highly purified recombinant neuronal antigens (Hu, Ri, and Yo) were further used to analyze target antigens of CAA. CAA were significantly increased in achalasia patients compared with controls when considering nuclear or cytoplasmic fluorescence patterns. (33% vs. 12%, P = 0.03 and 48% vs. 23%, P = 0.001 respectively). By immunoblot analysis, CAA did not target neuronal antigens, however 52/53 and 49 kDa bands were consistently detected. CAA positivity was not correlated to specific clinical features. The results are along with previous studies demonstrating high CAA prevalence in achalasia patients. When reviewing technical protocols and interpretation criteria, several discrepancies which could explain controversies between studies were noted.

[Efficacy and safety of Adalimumab in Crohn's disease]. / Indications et résultats de l'adalimumab au cours de la maladie de Crohn.

BACKGROUND: Adalimumab is the first subcutaneously self administered fully human anti-TNFa. AIM: To determine efficacy and safety of Adalimumab therapy in Crohn disease. METHODS: Literature review. RESULTS: Adalimumab has been evaluated for its effect in inducing and maintaining remission and its steroid-sparing effect of refractory Crohn's disease. In addition, it offers a significant treatment option in patients who have lost response to or become intolerant to Infliximab. Results also suggest efficacy of Adalimumab in fistulising Crohn's disease but more studies are needed. Adalimumab was well tolerated and studies show that all anti-TNF inhibitors have similar safety profiles.

Metabolic syndrome is associated with gastroesophageal reflux disease based on a 24-hour ambulatory pH monitoring.

Several studies have focused on the relationship between metabolic syndrome and gastroesophageal reflux disease (GERD). They were based on GERD complications, whereas little is known about the association between metabolic syndrome and objectively measured esophageal acid exposure. The aim of our study was to assess the relationship between metabolic syndrome and GERD based on a 24-hour pH testing. It was a cross-sectional study including 100 consecutive patients who underwent a 24-hour pH-metry monitoring and were assessed for the five metabolic syndrome components as well as for body mass index (BMI). Among the 100 patients, 54 had a pathological acid GERD. The 46 GERD-free patients represented control group. Sex distribution was comparable between both groups but GERD patients were older than controls (44.59 vs. 37.63 years, P= 0.006) and more often obese or with overweight (83.3 vs. 60.9%, P= 0.01). Frequency of metabolic syndrome as a whole entity was higher among patients with GERD than those without GERD (50 vs. 19.56%; P= 0.002) with a crude odds ratio of 4.11 (95% confidence interval: 1.66-10.14). Multivariate regression analysis showed that metabolic syndrome as well as an age ≥ 30 years were independent factors associated to GERD but not BMI and sex. Abnormal waist circumference and fasting glucose level ≥ 100 mg/L were the only independent factors among the five components of metabolic syndrome. Metabolic syndrome but not BMI was an independent factor associated to GERD. These results confirm the hypothesis that central obesity is associated to GERD.

Effect of pantoprazole in patients with chronic laryngitis and pharyngitis related to gastroesophageal reflux disease: clinical, proximal, and distal pH monitoring results.

Few studies had evaluated the results of proton pump inhibitors on distal and proximal pH recording using a dual-channel probe. The aim of this study was to determine the clinical and pH-metric effect of treatment with pantoprazole 80 mg for 8 weeks in patients with ear, nose, and throat (ENT) manifestations of gastroesophageal reflux disease associated with pathological proximal acid exposure. We conducted a prospective open study. Patients included had to have chronic pharyngitis or laryngitis, and a pathological gastroesophagopharyngeal reflux. All patients received treatment with pantoprazole 80 mg daily for 8 weeks. One week after the end treatment, patients had a second ENT examination and a 24-hour pH monitoring using dual-channel probe. We included 33 patients (11 men, 22 women). A pathological distal acid reflux was found in 30 patients (91%). After treatment, the improvement of ENT symptoms was found in 51.5% of patients. Normalization of 24-hour proximal esophageal pH monitoring was observed in 22 patients (66%). After treatment, the overall distal acid exposure, the number of distal reflux events, and the number of reflux during more than 5 minutes were significantly decreased (respectively: 19.4% vs 7.2% [P < 0.0001], 62.7 vs 28.4 [P < 0.0001], and 10.4 vs 3.9 [P < 0.0001] ). Similarly, in proximal level, the same parameters were significantly decreased after treatment (respectively: 6.8% vs 1.6% [P < 0.0001], 32.6 vs 8.1 [P < 0.0001], and 3.4 vs 0.6 [P= 0.005] ). Treatment with pantoprazole reduced the frequency and severity of gastroesophagopharyngeal acid reflux in patients with chronic pharyngitis and laryngitis.

Les infections au cours des maladies inflammatoires chroniques de l'instestin

Pre-requis:les infections sont frequentes au cours des maladies inflammatoires chroniques de l'intestin.Elles sont associees a un risque eleve de mortalite.But:preciser les differentes infections survenants chez les malades atteints des maladies Crohn et de rectocolite hemorragique et leurs moyens de preventions .Materiel et methodes: revue de la litterature .Resultats: les infections survenant au cours des poussees peuvent expliquer la resistance aux traitements de la maladie. Il s'agit le plus souvent des infections a clostridium difficile et a cytomegalovirus.Les infections a Epstein -Barr virus majorent le risque de lymphomes chez les malades sous azathioprine. Les infections opportunistes sont relativement frequentes au cours des maladies inflammatoires chroniques de l'intestin; en particulier en cas de prise d'un ou de plusieurs immunosuppresseurs. prevention de ces infections opportunistes se base sur un bilan pre-therapeutique complet; les vaccinations chez les patients immunodeprimes et la chimioprophylaxie dans certaines situations .Conclusion: la connaissance des differentes infections pouvant survenir chez les malades attientes de maladies inflammatoires chroniques de l'intestin est primordiale.Le traitement de ces infections est associees a une meilleures reponse aux traitements de la maladie et a une reduction de la mortalite en cas d'infection opportuniste

Correlation between levels of C-reactive protein and clinical activity in Crohn's disease.

AIMS: To determine the factors associated with an increased C-reactive protein level in Crohn's disease patients and to seek a correlation between the C-reactive protein value and the Crohn's disease activity index. METHODS: We prospectively studied 103 Crohn's disease patients, 76% of whose disease was active at the time of inclusion. C-reactive protein measurement was carried out on all patients. An increased C-reactive protein level was defined as >/=10mg/L. RESULTS: The median C-reactive protein rate was 53.9mg/L (ranging from 1 to 228mg/L). An increased C-reactive protein was found in 77 patients (75%). By univariate analysis, ileocolic localization, severity of the flare, erythrocyte sedimentation rate, leukocyte and platelet count, fibrinogen, albumin, serum calcium and Crohn's disease activity index were found to be associated to elevated C-reactive protein values. By multivariate analysis, independent factors associated with an increased C-reactive protein level were: ileocolic localization (p=0.02; OR [95% CI]: 2.84 [1.25-9.52]) and moderate or severe disease activity (p=0.001; OR [95% CI]: 4.20 [1.92-8.64]). A statistically significant association between the Crohn's disease activity index score and the C-reactive protein level was found in our study (r=0.302; p=0.001). The optimal C-reactive protein threshold value that separates patients with moderate to severe disease (Crohn's disease activity index>220) from the others was calculated to be 19mg/L with a sensitivity of 76.4% and a specificity of 56.2%. CONCLUSION: The C-reactive protein level is correlated to disease activity in Crohn's disease. Its role seems to be essential in predicting moderate and severe disease activity.

The 119 kDa and 124 kDa polyproteins of arabis mosaic nepovirus (isolate S) are encoded by two distinct RNA2 species.

Arabis mosaic virus (ArMV) is a nepovirus that is serologically distantly related to grapevine fanleaf virus (GFLV). Both ArMV and GFLV induce grapevine degeneration disease. Several ArMV isolates, unlike isolates of GFLV, produce upon in vitro translation of RNA2 a polyprotein (P2) that forms a double band in polyacrylamide-SDS gels. Cloning of full-length copies of RNA2 of an ArMV isolate from grapevine (ArMV-S) revealed that this isolate contained two RNA2s of different length, called RNA2-U and RNA2-L. The two species were not readily separated by electrophoresis of the virion RNA under denaturing gel electrophoresis conditions but could be distinguished by analysis of primer extension and in vitro translation products. The size difference of the two RNA2s is due mostly if not exclusively to differences in their coding regions. The 124 kDa RNA2-U-encoded polyprotein P2' and the 119 kDa RNA2-L-encoded polyprotein P2", which co-migrate, respectively, with the upper and lower polyprotein bands produced by RNA2 of ArMV-S, were more than 95% identical except in their N-terminal domains. In vitro maturation experiments and sequence comparisons indicate that the N-terminal products of P2' and P2" have a molecular mass of 31 kDa and 26 kDa. The genomic organization proposed is similar to that of GFLV RNA2.

Protection against virus infection in tobacco plants expressing the coat protein of grapevine fanleaf nepovirus.

Grapevine fanleaf nepovirus (GFLV) is responsible for the economically significant "court-noué" disease in vineyards. Its genome is made up of two single-stranded RNA molecules (RNA1 and RNA2) which direct the synthesis of polyproteins P1 and P2 respectively. A chimeric coat protein gene derived from the C-terminal part of P2 was constructed and subsequently introduced into a binary transformation vector. Transgenic Nicotiana benthamiana plants expressing the coat protein under the control of the CaMV 35S promoter were engineered by Agrobacterium tumefaciens-mediated transformation. Protection against infection with virions or viral RNA was tested in coat protein-expressing plants. A significant delay of systemic invasion was observed in transgenic plants inoculated with virus compared to control plants. This effect was also observed when plants were inoculated with viral RNA. No coat protein-mediated cross-protection was observed when transgenic plants were infected with arabis mosaic virus (ArMV), a closely related nepovirus also responsible for a "court-noué" disease.

Biologically active transcripts from cloned cDNA of genomic grapevine fanleaf nepovirus RNAs.

Transcripts were produced in vitro by run-off transcription from full-length cDNA of RNA1 and RNA2 of grapevine fanleaf nepovirus (GFLV; isolate F13) cloned downstream from a bacteriophage RNA polymerase promoter. These transcripts, which possess a 5' terminal cap structure and a non-viral G residue instead of the naturally occurring genome-linked viral protein (VPg), are infectious to Chenopodium quinoa protoplasts when inoculated by electroporation. Synthetic RNA1 alone replicated in protoplasts. Inoculation of C. quinoa plants with synthetic RNA1 plus RNA2 produced symptoms similar to, but weaker, than those observed in plants infected with natural GFLV 6 to 8 days post-inoculation. Co-inoculated RNA1 and RNA2 were able to replicate and spread systemically in plants but RNA1 alone produced no symptoms and was not detected in non-inoculated leaves, suggesting that virus spread requires RNA2. Analysis of the genomic RNAs in plants infected with transcripts showed that the non-viral G at their 5' ends was not retained in the progeny.

In vitro expression of a chimeric coat protein gene from Grapevine Fanleaf virus (strain F 13).

The coat protein (CP) cistron of Grapevine Fanleaf virus strain F13 (GFLV-F13) has been located in the C-terminal region of the 122k polyprotein encoded by the genomic RNA 2 [Serghini et al. (1990) J. Gen. Virol. 71: 1433-1441]. A chimeric CP gene of GFLV-F13 including a short sequence corresponding to 3 restriction sites, the leader sequence of the GFLV-F13 satellite RNA and an initiation codon was constructed. Transcripts from this construct were translated in wheat germ extract with equal efficiency to form a 56k protein which comigrates on PAGE with the GFLV-F13 CP and a protein of 52k. Both species react with GFLV-F13 CP-specific antibodies. Deletions in the 5' region of the CP gene show that the 56k protein is initiated at the first AUG after the satellite leader and the 52k protein at the second in-frame AUG. Transcripts with a 142 nt deletion including the two AUG codons from the 5' end of the CP gene are not efficiently expressed in vitro, no major translation product being detected.

RNA2 of grapevine fanleaf virus: sequence analysis and coat protein cistron location.

The nucleotide sequence of the genomic RNA2 (3774 nucleotides) of grapevine fanleaf virus strain F13 was determined from overlapping cDNA clones and its genetic organization was deduced. Two rapid and efficient methods were used for cDNA cloning of the 5' region of RNA2. The complete sequence contained only one long open reading frame of 3555 nucleotides (1184 codons, 131K product). The analysis of the N-terminal sequence of purified coat protein (CP) and identification of its C-terminal residue have allowed the CP cistron to be precisely positioned within the polyprotein. The CP produced by proteolytic cleavage at the Arg/Gly site between residues 680 and 681 contains 504 amino acids (Mr 56019) and has hydrophobic properties. The Arg/Gly cleavage site deduced by N-terminal amino acid sequence analysis is the first for a nepovirus coat protein and for plant viruses expressing their genomic RNAs by polyprotein synthesis. Comparison of GFLV RNA2 with M RNA of cowpea mosaic comovirus and with RNA2 of two closely related nepoviruses, tomato black ring virus and Hungarian grapevine chrome mosaic virus, showed strong similarities among the 3' non-coding regions but less similarity among the 5' end non-coding sequences than reported among other nepovirus RNAs.

The nucleotide sequence of satellite RNA in grapevine fanleaf virus, strain F13.

The nucleotide sequence of cDNA copies of grapevine fanleaf virus (strain F13) satellite RNA has been determined. The primary structure obtained was 1114 nucleotides in length, excluding the poly(A) tail, and contained only one long open reading frame encoding a 341 residue, highly hydrophilic polypeptide of Mr37275. The coding sequence was bordered by a leader of 14 nucleotides and a 3'-terminal non-coding region of 74 nucleotides. No homology has been found with small satellite RNAs associated with other nepoviruses. Two limited homologies of eight nucleotides have been detected between the satellite RNA in grapevine fanleaf virus and those in tomato black ring virus, and a consensus sequence U.G/UGAAAAU/AU/AU/A at the 5' end of nepovirus RNAs is reported. A less extended consensus exists in this region in comovirus and picornavirus RNA.