Taoufik Najjar

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

BackgroundThe 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.AimTo evaluate the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and to detect the mutations involved in clarithromycin resistance.Materials and methods273 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.ResultsNo 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.ConclusionLocal 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.

Cerebral thrombosis in inflammatory bowel disease: A report of four cases

The risk of thromboembolism is increased in inflammatory bowel disease and its symptoms may be overlooked. The commonest are deep vein thrombosis and pulmonary emboli. Cerebral thrombosis, in a particular stroke, is rare. Furthermore, its treatment can be complex. We present the cases of 4 patients with cerebral vascular involvement.

Interleukin-18 gene polymorphisms in tunisian patients with inflammatory bowel disease.

Aim: Interleukin (IL)-18 can regulate the Th2-mediated immune response and it may be involved in the pathogenesis of Th1 and Th2 chronic inflammatory diseases. This study sought to detect a possible association between two single nucleotide polymorphisms (SNPs) (–137G/C and –607C/A) in the IL-18 gene promoter region and susceptibility to inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) in the Tunisian population. Methods: The (–137G/C and –607C/A) IL-18 polymorphism was analyzed in 105 patients with CD, 59 patients with UC, and 100 controls using the sequence-specific polymerase chain reaction method. Results: The distribution of allele and genotype frequencies illustrate that the –137G/G genotype frequency was significantly higher in UC than in controls (p value corrected (pc) = 0.038). On the other hand, we found a statistically significant association (pc = 0.033) between genotype AA of the IL-18 gene promoter (–607C/A) polymorphism in UC patients and the distal localization of the lesions. In CD, no significant differences were observed at positions –607 and –137. The analysis of IBD patients according to clinical behavior revealed no difference. Conclusion: The two SNPs at position –607 (C/A) and –137 (G/C) in the promoter region of the IL-18 gene was associated with the development of UC but not CD, providing a strong support for an IBD susceptibility gene in the region surrounding IL-18. It remains to be determined precisely how the IL-18 alleles influence the pathogenesis of IBD.

Association between sHLA-G and HLA-G 14-bp deletion/insertion polymorphism in Crohn’s disease

The aim of this study was to evaluate the association between the HLA-G 14-bp deletion/insertion (Del/Ins) polymorphism and soluble (s) HLA-G production in patients with Crohns disease (CD). We analyzed also the sHLA-G molecules by ELISA and western blot in plasma samples. Among unselected patients, the 14-bp Del/Ins polymorphism was not significantly associated with increased CD risk neither for alleles (P = 0.371) nor for genotypes (P = 0.625). However, a significant association was reported between the 14-bp Del/Ins polymorphism and CD, in particular in young-onset CD patients for alleles [P = 0.020, odds ratio (OR) = 2.438, 95% confidence interval (CI): 1.13-5.25] but not with adult-onset CD patients. A significant association was reported concerning the genotype Ins/Ins for young-onset CD patients (P = 0.029, OR = 3.257, 95% CI: 1.08-9.77). We observed also a significant increase in sHLA-G measured by ELISA in CD patients compared to controls (P = 0.002). The 14-bp Del/Del and 14-bp Del/Ins genotypes are the high HLA-G producers. Among sHLA-G(positive) patients, 43% of subjects present dimers of HLA-G. The presence of dimers seems to be related to the advanced stages of the disease. The 14-bp Del/Ins polymorphism is associated with an increased risk of CD particularly in young-onset CD patients and controls sHLA-G plasma levels. Dimers of sHLA-G are frequent in advanced disease stages. The above findings indicate that the genetic 14-bp Del/Ins polymorphism in exon 8 of the HLA-G gene is associated with the risk of CD and suggest a role for sHLA-G as a prognostic marker for progressive disease.

Systemic lupus erythematosus and celiac disease.

Joint Bone Spine - In Press.Proof corrected by the author Available online since vendredi 30 septembre 2011

Variceal band ligation in the prevention of variceal bleeding: a multicenter trial.

Background/Aim: Variceal bleeding is a life-threatening complication of portal hypertension with a high probability of recurrence. Treatment to prevent first bleeding or rebleeding is mandatory. The study has been aimed at investigating the effectiveness of endoscopic band ligation in preventing upper gastrointestinal bleeding in patients with portal hypertension and to establish the clinical outcome of patients. Patients and Methods: We analyzed in a multicenter trial, the efficacy and side effects of endoscopic band ligation for the primary and secondary prophylaxis of esophageal variceal bleeding. We assigned 603 patients with portal hypertension who were hospitalized to receive treatment with endoscopic ligation. Sessions of ligation were repeated every two to three weeks until the varices were eradicated. The primary end point was recurrent bleeding. Results: The median follow-up period was 32 months. A total of 126 patients had recurrent bleeding. All episodes were related to portal hypertension and 79 to recurrent variceal bleeding. There were major complications in 51 patients (30 had bleeding esophageal ulcers). Seventy-eight patients died, 26 deaths were related to variceal bleeding and 1 to bleeding esophageal ulcers. Conclusions: A great improvement in the prevention of variceal bleeding has emerged over the last years. However, further therapeutic options that combine higher efficacy, better tolerance and fewer side effects are needed.

Investigation of DNA Sequence in the Basal Core Promoter, Precore, and Core Regions of Hepatitis B Virus from Tunisia Shows a Shift in Genotype Prevalence

Background In this study, we evaluated the prevalence of the most common mutations occurring in Enhancer II (EnhII), Basal Core Promoter (BCP), Precore (PC), and Core (C) regions of hepatitis B virus (HBV) genome. Objectives We also investigated the correlation between HBV variants, their genotypes, and patients’ HBe antigen (HBeAg: soluble shape of the capsid antigen) status. Patients and Methods We retrieved viral DNA from 40 serum samples of Tunisian patients positive for hepatitis B surface antigen (HBsAg) and HBV DNA, amplified the above mentioned regions using specific primers, and sequenced the corresponding PCR (polymerase chain reaction) products. For further analysis purpose, the patients were divided into two groups: Group1 including 34 HBeAg-negative patients and Group2 with 6 HBeAg-positive patients. Results Twenty-one patients (52.5%) showed PC G1896A mutation and 11 (27.5%) carried A1762T/G1764A double mutations. These mutations were more frequent in HBeAg-negative patients than that in HBeAg-positive ones. Indeed, 58.8% of patients bearing G1896A mutation were HBeAg-negative while 16.7% were positive. In patients bearing T1762/A1764 double mutation, 29.4% were positive and 16.7% were negative. In addition, the A1896 mutation was restricted to HBV isolates that had wild-type T1858, while C1858 was rather linked to the occurrence of T1762/A1764 mutation. Interestingly, this study revealed a high frequency of genotype E. This frequency was important as compared to that of genotype D known to be predominant in the country as delineated in previous studies. Conclusions Previous results supported and showed that HBV strains present in Tunisia belonging to genotype D and, to a lesser extent, to genotype E, were prone to mutations in BCP/ PC regions. This observation was more obvious in HBV isolates from asymptomatic chronic carriers (AsC). The high mutational rates observed in our study might result from a mechanism of viral escape that plays an important role in the loss of HBeAg.

Lynch syndrome in Tunisia: first description of clinical features and germline mutations

PurposeHigh rates of early colorectal cancers (CRC) are observed in Tunisia suggesting genetic susceptibility. Nevertheless, up to now, no molecular study has been performed in the Tunisian population. In our research, we evaluated the clinical characteristics of Tunisian families suspected of Lynch syndrome and the contribution of DNA mismatch repair (MMR) genes.MethodsThirty-one unrelated families suspected of Lynch syndrome were studied. Probands were tested for the presence of germline mutations in the MMR genes MLH1, MSH2, MSH6 and in MUTYH. Available tumours were analysed for microsatellite instability and expression of MMR proteins. Detailed family and medical histories were collected.ResultsA total of 134 cancers were noted in the 31 families, the most frequent type of cancer corresponding to CRC (69%), followed by uterine cancer (7.5%). Germline mutations were identified in 11 (35.5%) families (six MSH2, five MLH1, including seven novel mutations), seven of which fulfilled the Amsterdam criteria (sensitivity, 63.6%; positive predictive value, 58.3%). Noteworthy, germline mutations were detected in 52.6% of male patients tested, but in only 8.3% of females (p = 0.02). Moreover, CRC were essentially left sided in families without detected mutation (p = 0.017). Ages of onset of cancers and tumour spectrum were very similar in families with or without MMR germline mutation, contrasting with previous studies performed in other populations.ConclusionsMMR genes contribute significantly to CRC susceptibility in the Tunisian population. However, the cause of early CRC susceptibility remains unknown in most cases, especially in women and in patients with early left colon or rectal cancer.

Malignant epithelioid hemangioendothelioma: a case report.

Malignant epithelioid hemangioendothelioma (EH) is a rare tumor of vascular origin. We report a case of a woman who was found to have multiple hepatic masses in the right lobe of the liver on radiologic investigations, initially misdiagnosed as a metastatic carcinoma. The diagnosis of EH was made on histopathological study and confirmed by immunohistochemistry, which showed diffuse response for CD34 marker and no response to tissue CEA, HMB-45 or S-100 protein. Partial hepatectomy was made with good results.

Infiximab for treatment of systemic amyloidosis associated with Crohn's disease.

Dear Sir, Systemic AA amyloidosis is a rare but serious complication of Crohns Disease (CD) associated with 0.9–3% cases1–3.To date, there has been no effective treatment for secondary amyloidosis; treatment has consisted in treating the underlying inflammatory disease. Various therapeutic attempts such as azathioprine, colchicine, dimethylsulfoxide, and elemental diets have been tried and suggested to delay the progression of renal amyloidosis but their efficacy has not been fully elucidated. In recent years, it has been reported that the use of more powerful anti-inflammatory drugs such as biological agents may improve the clinical course of AA-amyloidosis in rheumatic4 and inflammatory bowel disease patients.3 Here we report the case of a patient with systemic amyloidosis associated with CD and s pondyloarthropathy treated with Infliximab. A 30-year-old non smoker male was diagnosed with ileal CD and spondyloarthropathy in 2003 at the age of 23. The patient required …