TLR3 and TLR4 SNP variants in the liver disease resulting from hepatitis B virus and hepatitis C virus infection.

BACKGROUND: Chronic infection with hepatitis B (HBV) and C virus (HCV) is linked with a pro-inflammatory state, predisposing to cirrhosis and liver cancer, particularly hepatocellular carcinoma (HCC). A role for Toll-like receptor (TLR) signalling in hepatocarcinogenesis was recently documented. We hypothesised a link TLR3 and TLR4 polymorphisms and HCC, as surrogates for the significance of TLR signalling in the promotion and initiation of HCC. MATERIALS AND METHODS: We recruited 174 HCV-infected patients, 100 HBV-infected patients and 360 healthy control subjects. TLR3 (rs3775290) and TLR4 (rs4986790) genotyping was done by PCR-restriction fragment length polymorphisms (PCR-RFLP), LFTs and AFP by standard routine techniques. Liver fibrosis was assessed clinically by the Fibrotest and Actitest. RESULT: The TLR3 rs3775290 minor T genotype was linked with increased risk of chronic HBV (P = 0.05) and HCV (P = 0.031) infection. The TLR4 rs4986790 minor G genotype was linked with significantly increased risk for HBV/HCV chronic infection (P < 0.001). Subgroups analyses indicated decreased risk of HBV-related HCC in relation to TLR3 rs3775290 CC/CT genotype (P = 0.022), with increased risk ascribed to the minor (T) allele (P = 0.04). Likewise, TLR4 rs4985790 minor (GG) genotype was positively associated with HBV-linked HCC (P < 0.001). Furthermore, a link between TLR3 TT (P < 0.001) andTLR4 GG (P = 0.04) minor genotypes was noted in relation to increased risk of HCV-related disease. CONCLUSION: TLR3 and TLR4 polymorphisms are promising biomarkers of liver cirrhosis and cancer associated with HBV and HCV infection.

Local pro-inflammatory cytokine and nitric oxide responses are elevated in patients with pterygium.

Pterygium is a common ocular surface disease observed in humans. Chronic ultraviolet (UV) exposure is extensively recognized as an aetiological factor in the pathogenesis of this disease. This hypothesis is sustained by epidemiological and histopathological data in relation to UV injured skin. Although some findings have indicated that genetic factors, anti-apoptotic and immunological mechanisms are involved in the pathogenesis of pterygium, the mechanism by which it develops remains poorly understood. In this study, we analysed the in vivo production of IL-17A, IL-6, IL-10 and nitric oxide (NO) in the tears and sera from Algerian patients. Interestingly, we observed that IL-6, IL-17A and NO production in the tears and sera of all patients was strongly associated with inflammatory infiltration, NOS2, NF-κB and Bcl2 expression in pterygia biopsies. Collectively, our results indicate a relationship between local inflammation and anti-apoptotic processes in pterygium disease, leading to both tissue damage and enhanced cellular proliferation.

Interleukin-1ß, Interleukin1-Ra, Interleukin-10, and tumor necrosis factor-α polymorphisms in Tunisian patients with rheumatoid arthritis.

OBJECTIVES: The aim of this study was to investigate the role of IL-1ß (-511C>T), TNFα (-308 G>A), IL-10 (-1082 G>A) and IL-1RN VNTR polymorphisms in the susceptibility to rheumatoid arthritis (RA) in Tunisians. PATIENTS AND METHODS: Using PCR-based methods, 104 RA patients and 150 healthy controls were investigated. We compared allele and genotype frequencies in RA patients versus controls and analyzed their correlations with erosive form (EF). RESULTS: IL1-RN VNTR A1A3 genotype is associated with higher risk of RA (P=0.012, OR=4.31). Among the cases, males who carry this genotype were more exposed to RA (P=0.044, OR=8, 47). For IL1- ß gene, a significantly higher frequency of the -511C/C genotype was observed in RA patients in comparison to controls (P=0.013, OR=2.45). This higher frequency was especially observed in women (P=0,003, OR=3.42). In contrast, IL10-1082G/G genotype was less common in patients (P=0.046, OR=0.46). According to EF, men carrying IL1-RN VNTR A1A3 (P=0.005 OR=5.28) and IL1-ß-511C/C (P=0.015 OR=2.61) genotypes develop non EF of RA. Moreover, TNFα-308 A allele (P=0.024, OR=1.84) and A/A genotype (P=0.033, OR=3.1) were positively associated to EF of RA. However, G allele (P=0.024, OR=0.31) and GG genotype (P=0.31, OR=0.031) of the TNFα-308 were protectors. CONCLUSION: Our results indicated that IL-1RN VNTR, IL-1ß (-511C>T) and IL-10 (-1082 G>A) are associated with susceptibility to RA, and that IL-1RN VNTR, IL-1ß (-511C>T) and TNFα (-308 G>A) are associated with severity of RA.

[Primary epiploic appendicitis: CT diagnosis for conservative treatment]. / Les appendicites épiploïques primitives: diagnostic tomodensitométrique pour un traitement conservateur.

OBJECTIVE: Primary epiploic appendicitis is an uncommon, self-limited disease with spontaneous resolution. Diagnosis is usually made at surgery as the disease is generally mistaken for acute appendicitis or sigmoid diverticulitis. CT allows a non-invasive diagnosis, thus avoiding unnecessary surgery. The condition can be managed conservatively with the use of analgesic drugs only, and clinical evolution is uneventful. The aim of this study is to report the CT features of this pathologic process before and after medical treatment by analgesics. PATIENTS AND METHOD: Six patients (4 men and 2 women aged from 23 to 70 year old mean; 29 year old) underwent abdominal CT scan because of acute abdominal pain located in the left lower quadrant (n = 3) and right lower quadrant (n = 3). No patient had fever. Laboratory findings were normal in all cases. Follow-up CT scans were obtained in 4 patients respectively at 2, 4, 8 and 80 weeks. RESULTS: CT scan showed in all cases a fatty mass located to the anterolateral wall of the colon, delineated by an hyper attenuating rim. Infiltration of the pericolic fat was noted in all cases. Follow up CT scans obtained in 4 patients showed that the inflammatory signs had cleared in all cases, the lesion had disappeared (n = 2), decreased in size (n = 1) or a residual paracolic node was observed (n = 1). CONCLUSION: Primary epiploic appendicitis is a rare disease. Knowledge of CT signs allowed the correct diagnosis and a conservative management.

Performance characteristics of magnetic resonance cholangiography in the staging of malignant hilar strictures.

BACKGROUND: Magnetic resonance cholangiography (MRC) is currently under investigation for non-invasive biliary tract imaging. AIM: To compare MRC with endoscopic retrograde cholangiography (ERC) for pretreatment evaluation of malignant hilar obstruction. METHODS: Twenty patients (11 men, nine women; median age 74 years) referred for endoscopic palliation of a hilar obstruction were included. The cause of the hilar obstruction was a cholangiocarcinoma in 15 patients and a hilar compression in five (one hepatocarcinoma, one metastatic breast cancer, one metastatic leiomyoblastoma, two metastatic colon cancers). MRC (T2 turbo spin echo sequences; Siemens Magnetomvision 1.5 T) was performed within 12 hours before ERC, which is considered to be the ideal imaging technique. Tumour location, extension, and type according to Bismuth's classification were determined by the radiologist and endoscopist. RESULTS: MRC was of diagnostic quality in all but two patients (90%). At ERC, four patients (20%) had type I, seven (35%) had type II, seven (35%) had type III, and two (10%) had type IV strictures. MRC correctly classified 14/18 (78%) patients and underestimated tumour extension in four (22%). Successful endoscopic biliary drainage was achieved in 11/17 attempted stentings (65%), one of which was a combined procedure (endoscopic + percutaneous). One patient had a percutaneous external drain, one had a surgical bypass, and in a third a curative resection was attempted. Effective drainage was not achieved in six patients (30%). If management options had been based only on MRC, treatment choices would have been modified in a more appropriate way in 5/18 (28%) patients with satisfactory MRC. CONCLUSION: MRC should be considered for planning treatment of malignant hilar strictures. Accurate depiction of high grade strictures for which endoscopic drainage is not the option of choice can preclude unnecessary invasive imaging.

[Preoperative evaluation of gastric adenocarcinomas: comparison of CT results with surgical and patholgic results]. / Bilan préopératoire des adénocarcinomes gastriques: comparaison des résultats de la tomodensitométrie avec les constations peropératoires et les résultats anatomo-pathologiques.

PURPOSE: The objective of our study was to reassess the value of CT scan in the preoperative evaluation of gastric adenocarcinoma, using surgical and pathologic findings as the reference standard. MATERIALS AND METHODS: Forty-five patients who had preoperative CT scan for gastric carcinoma were retrospectively included in the study. Images were analyzed by two readers working in consensus with respect to tumor detection, tumor location, depth of invasion, involvement of adjacent organs, lymph node involvement and presence of peritoneal carcinomatosis. RESULTS: Gastric tumor was visible in 91% of cases. Accurate tumor localization was obtained in 50% of cases. Depth of tumor penetration was correctly evaluated in 40% of the cases. Evaluation of regional and distant lymph node metastases was correct in 54% and 64% of cases, respectively. Peritoneal carcinomatosis was depicted in 17% of cases. CONCLUSION: CT scan allows detection of gastric adenocarcinoma in the majority of cases. However, this technique markedly underscores the extent of gastric adenocarcinoma. Therefore, CT scan should not be used to determine the preoperative staging of gastric adenocarcinoma.

Use of magnetic resonance cholangiography in the diagnosis of choledocholithiasis: prospective comparison with a reference imaging method.

BACKGROUND: Magnetic resonance cholangiography (MRC) is a new technique for non-invasive imaging of the biliary tract. AIM: To assess the results of MRC in patients with suspected bile duct stones as compared with those obtained with reference imaging methods. PATIENTS/METHODS: 70 patients (34 men and 36 women, mean (SD) age 71 (15.5) years; median 75) with suspected bile duct stones were included (cholangitis, 33; pancreatitis, three; suspected post-cholecystectomy choledocholithiasis, nine; cholestasis, six; stones suspected on ultrasound or computed tomography scan, 19). MR cholangiograms with two dimensional turbo spin echo sequences were acquired. Endoscopic retrograde cholangiography with or without sphincterotomy (n = 63), endosonography (n = 5), or intraoperative cholangiography (n = 2) were the reference imaging techniques used for the study and were performed within 12 hours of MRC. Radiologists were blinded to the results of endoscopic retrograde cholangiography and previous investigations. RESULTS: 49 patients (70%) had bile duct stones on reference imaging (common bile duct, 44, six of which impacted in the papilla; intrahepatic, four; cystic duct stump, one). Stone size ranged from 1 to 20 mm (mean 6.1, median 5.5). Twenty seven patients (55%) had bile duct stones smaller than 6 mm. MRC diagnostic accuracy for bile duct lithiasis was: sensitivity, 57.1%; specificity, 100%; positive predictive value, 100%; negative predictive value, 50%. CONCLUSIONS: Stones smaller than 6 mm are still often missed by MRC when standard equipment is used. The general introduction of new technical improvements is needed before this method can be considered reliable for the diagnosis of bile duct stones.

Tuberculous colitis mimicking Crohn's disease: utility of computed tomography in the differentiation.

The case of a 50-year-old woman with pathologically proven tuberculous colitis is reported. Clinical course, single-contrast barium enema, and colonoscopy suggested Crohn's disease. Computed tomography allowed the correct diagnosis of tuberculous colitis as it showed asymmetric thickening of the colonic wall and enlarged necrotic lymph nodes. This case suggests that the diagnosis of tuberculous colitis may be difficult and raises the differential diagnosis with Crohn's disease. Our observation suggests that computed tomography can be helpful for the diagnosis and may avoid unnecessary exploratory laparotomy.

Digestion and tolerance of lactose from yoghurt and different semi-solid fermented dairy products containing Lactobacillus acidophilus and bifidobacteria in lactose maldigesters--is bacterial lactase important?

OBJECTIVE: To compare the digestibility and tolerance of lactose from three semi-solid fermented dairy products with the same amount of lactose but different lactase contents and bacterial cultures in lactase deficient adults. DESIGN: Measurement of breath hydrogen (H2) concentration and of clinical symptoms after consumption of the test meals. SETTING: Metabolic ward for healthy volunteers, INSERM U290, Hôpital St. Lazare, Paris. SUBJECTS: Fifteen lactase-deficient healthy adult volunteers (20-45 y) started the study. One subject became a non-H2-producer during the study; therefore the results of 14 subjects are presented. INTERVENTION: Each subject consumed, on four different days and in random order, after a 12 h fast, three semisolid test meals containing 18 g of lactose, and a 10 g dose of lactulose which allowed calculation of lactose malabsorption. The three meals were: traditional yoghurt, fermented milk (Ofilus) that contained Lactobacillus acidophilus and Bifidobacterium sp., and a similar product 'Bulgofilus' enriched with Lactobacillus bulgaricus to increase the lactase content. RESULTS: Compared with lactulose, the sum of symptoms was significantly lower for Bulgofilus (P = 0.05), and bloating was less severe for Ofilus (P = 0.06). Between the fermented milks, there were no differences. The area under the breath H2 curve was significantly lower for each fermented milk when compared to lactulose (P < 0.0001). The degree of maldigestion of lactose did not differ significantly between the products; it was 21 +/- 3% (range 6-52) for Ofilus, 21 +/- 3% (range 6-44) for Bulgofilus, and 18 +/- 3% (range 3-43) for yoghurt. CONCLUSION: Despite the differences in the lactase and bacterial content, lactose was as well digested and tolerated from the three different semi-sold fermented dairy products. This could be due to a slow gastric emptying of the semi-solid milk.

Gastro-jejunal digestion of soya-bean-milk protein in humans.

In order to determine how soya-bean proteins are digested and metabolized in the human intestine before colonic bacterial fermentation and to estimate their true digestibility, the gastro-jejunal behaviour of soya-bean proteins in water and in two other forms (a concentrated soya-bean-protein solution (isolate) and a drink composed of crude soya-bean proteins (soymilk)) was studied in humans. Experiments were carried out in eight healthy volunteers using a double-lumen steady-state intestinal perfusion method with polyethyleneglycol (PEG) as a non-absorbable volume marker. Gastric emptying and N and electrolyte contents of the jejunal digesta were analysed. Gastric half-emptying time (min) of the liquid phase after water ingestion (12.59 (SE 0.12)) was shorter (P < 0.05) than those for soymilk (37.74 (SE 11.57)) and isolate (36.52 (SE 11.23)). Electrolytic balances showed that for all meals, Na+, Cl- and K+ were secreted when Ca2+ was efficiently absorbed from the jejunal lumen. Gastro-jejunal N absorption for isolate and soymilk were 63 and 49% respectively, and were not significantly different from one another; after water ingestion, endogenous N was estimated to be 21 mmol. An estimate of the exogenous:endogenous values for the effluents was obtained from the amino acid compositions of soymilk and effluents after water or soymilk ingestion, indicating that 70% of the total N was exogenous and 30% endogenous. Under these conditions the endogenous fraction represented 31 mmol after soymilk ingestion and the gastro-jejunal N balance indicated that 54% of the soymilk was absorbed. This finding indicates that the true gastrojejunal digestibility of soya-bean proteins is similar to that of milk proteins.

Enterocolitis cystica profunda lesions in a patient with unclassified ulcerative enterocolitis.

Enteritis cystica profunda and diffuse colitis cystica profunda are exceedingly rare conditions. We report here the first case in which these two entities are associated in one patient. This 48-year-old woman presented initially with a solitary ulcer of the rectum and developed later deep ileal and colonic ulcerations with intervening normal mucosa, polypoid masses, and a dense fibrosis of the bowel wall. Colon and ileum specimens demonstrated submucosal mucous cysts and occasionally herniation of mucosal epithelium into the submucosa, which led to the diagnosis of enteritis and colitis cystica profunda. The exact nature of the underlying ileocolonic disease, which necessitated colectomy and extensive ileal resection, remained undetermined although an aggravating role of iterative surgical procedures is possible. Enteritis cystica profunda and diffuse colitis cystica profunda therefore seem to share a common pathogeny and have to be considered as lesions complicating an underlying disease rather than specific and autonomic diseases.

[Survival of Lactobacillus acidophilus and Bifidobacterium sp. in the small intestine following ingestion in fermented milk. A rational basis for the use of probiotics in man]. / Survie, dans l'intestin grêle, de Lactobacillus acidophilus et Bifidobacterium sp, ingerés dans un lait fermenté. Une base rationnelle à l'utilisation de probiotiques chez l'homme.

Oro-ileal intubation was performed in 6 healthy volunteers who ingested, either 100 g of a fermented milk containing 10(8)/g Lactobacillus acidophilus and 10(7)/g Bifidobacterium sp or sterilized fermented milk along with a meal in random order. Lactobacillus acidophilus and Bifidobacterium were counted in the ileal fluid which was aspirated continuously for 8 h, and flow rates were calculated using the constant slow infusion of PEG 4000. After ingestion of fermented milk but not after control, hourly ileal flow rates of Lactobacillus acidophilus and Bifidobacterium increased form 4.8 +/- 0.2 and 4.9 +/- 0.6 to 7.2 +/- 0.3 and 8.0 +/- 0.3, respectively (mean +/- SE log10 CFU). 8.3 +/- 0.2 Lactobacillus acidophilus and 8.8 +/- 0.1 Bifidobacterium were recovered in the ileum which represented 1.5 percent and 37.5 percent of the ingested bacteria, respectively. In conclusion, under usual conditions of fermented milk ingestion, a large number of living Lactobacillus acidophilus and Bifidobacterium pass through the upper gastrointestinal tract and reach the colon.