Paraoxonase 1 gene (Gln192–Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus

BackgroundParaoxonase 1 (PON1) is reported to have antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or type A/arginine (Arg) or type B polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported.ObjectivesTo investigate the relationship between PON1 gene (Gln¹⁹²–Arg) polymorphism and the presence, extent and severity of CAD in type 2 DM.MethodsThe study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into four groups: Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) nondiabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1(Gln¹⁹²–Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion.ResultsThe frequency of Gln allele (type A) was significantly higher in Group I and Group II compared to Group III and Group IV (62.5%, 60% vs. 38.3%, 31.25%, respectively, p < 0.001) while the frequency of Arg allele (type B + type AB) was significantly higher in ischemic groups (III and IV) compared to nonischemic groups (I and II) (61.7%, 68.75% vs. 37.5%, 40%, respectively, p < 0.001). Patients with CAD and DM (Group IV) have significantly higher severity score and vessel score than those with CAD only (Group III) (9.7 ± 2.97, 2.44 ± 0.56 vs. 6.99 ± 3.71, 1.67 ± 0.89, respectively, p < 0.001) Patients with vessel score 3 had significantly higher severity score and higher Arg allele frequency than patients with vessel score 2, the latter group had also significantly higher severity score and Arg allele frequency than patients with vessel score 1 (8.9 ± 2.79 vs. 5.21 ± 2.13 and 80.49% vs. 67.86%), (5.21 ± 2.13 vs. 3.11 ± 0.89 and 67.86% vs. 53.85%), p < 0.001 for all. In multivariate logistic regression analysis of different variables for prediction of CAD, age [OR 2.99, CI (1.11–10.5), p < 0.01], smoking [OR 4.13, CI (1.37–11.7), p < 0.001], low-density lipoprotein (LDL) cholesterol > 100 mg/dL [OR 4.31, CI (1.25–12.5), p < 0.001], high-density lipoprotein (HDL) cholesterol < 40 mg/dL [OR 5.11, CI (1.79–16.33), p < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67–13.57), p < 0.001] were significantly independent predictors of CAD.ConclusionArg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.     

Effectiveness of immunotherapy in children depends on place of living – A pilot study

BackgroundIt is considered that farm areas protect young patients from allergy and asthma due to high exposure to endotoxins. Allergen immunotherapy (AIT) is the only treatment of allergy modifying the immune response with the potential to change the natural history of allergic diseases. It seems that studies evaluating the efficacy of immunotherapy in large cohorts of allergic patients living in farm areas are needed to understand the influence of environment on immune response during AIT.Aim. To compare the clinical effectiveness of immunotherapy between children living in farm versus urban areas.Materials and methodsThis was a retrospective analysis of 87 children living in farm area (n = 42) and city area (n = 45), aged 8–16, who completed three years of subcutaneous immunotherapy due to allergic rhinitis/asthma. An AIT efficacy questionnaire has been designed to be filled in by the allergy specialist during a regular immunotherapy visit before and after AIT.ResultsWe observed significantly higher improvement in total score among children from farm area compared to children from city area (p < 0.001). Between-group differences in symptoms and drug scores did not reached the level of significance. Multivariate logistic regression analysis (adjustment for the effect of gender and type of allergy) showed that living in farm areas was independently associated with significant improvement in total score after immunotherapy (OR: 10.9; 95%CI: 3.7–32.2).ConclusionThe current analysis of the better AIT effectiveness in the farm population has shown the protective influence of environmental exposures on asthma and allergic rhinitis in our children.     

Enhanced proliferation in colorectal epithelium of patients with type 2 diabetes correlates with β-catenin accumulation

Aimsβ-Catenin accumulation promotes proliferation. However, the correlation between proliferation of colorectal epithelium and β-catenin in type 2 diabetes mellitus (DM) patients remains unclear.MethodsColorectal epithelium samples from distal ends of colorectal adenocarcinomas without histological aberrances were divided into two groups: DM patients with type 2 DM for more than 1 year (n = 27) and non-DM patients without hyperglycemia (n = 20). Samples from patients without colorectal epithelial disease or hyperglycemia served as a control group (n = 6). Proliferative index was calculated as the percentage of proliferating cell nuclear antigen positive cells. Wnt/β-catenin signaling was assessed immunohistochemically and phosphorylation of β-catenin was assessed by immunofluorescence.ResultsCompared with the non-DM or control group, the proliferative index and expression of lactate dehydrogenase A and Wnt/β-catenin signaling were significantly higher in the DM group (all p < 0.01). The proliferative index correlated positively with β-catenin expression (Spearman correlation coefficient = 0.55; p < 0.01). Reduced phosphorylation at serine 33/37 and increased phosphorylation at serine 675 of β-catenin were detected in the DM group (all p < 0.01).ConclusionsEnhanced proliferation, accompanied by increased aerobic glycolysis, was detected in colorectal epithelium of patients with diabetes. β-Catenin accumulation with altered phosphorylation correlated with the proliferative changes.     

The relationship between hs-CRP and asthma control test in asthmatic patients

BackgroundHigh sensitive C-reactive protein (hs-CRP) has been shown to be associated with asthma in recent studies. However, the relationship between hs-CRP and the control of asthma has not been clearly identified yet.ObjectiveTo investigate the association of hs-CRP with asthma control test (ACT), which reveals the degree of asthma control, and to compare hs-CRP in adults with mild and moderate asthma in chronic, stable asthmatic patients.MethodsThirty patients with physician-diagnosed asthma (11 mild, 19 moderate), and 30 healthy patients were enrolled in the study. In addition to medical history and physical examination, asthma was assessed according to GINA guideline. Respiratory function tests (RFT) and ACT were performed. The serum hs-CRP levels of all cases patients were measured.ResultsThe levels of hs-CRP in asthmatic patients were significantly higher than those in the control cases (p = 0.002). The serum hs-CRP levels in the moderate asthmatics were significantly higher than those in the mild asthmatic ones (p = 0.04). When asthmatic cases were divided into two groups according to ACTs; the levels of hs-CRP in the groups of ACT ≤ 20 (uncontrolled groups) were significantly higher than the groups of ACT ≥ 20 (controlled groups) (p = 0.02). The hs-CRP levels showed significant correlations with ACT (p = 0.00, r = ?0.91) and asthma severity (p = 0.04, r = 038) in asthmatic patients.ConclusionIn conclusion it was shown that hs-CRP is related with asthma severity and ACT, and hs-CRP is a potential sensitive marker which reveals the severity and the control of asthma.     

A comparative study of insulin resistance for Saudi and Caucasian subjects across a range of glycaemic categories

AimSaudi and Caucasian subjects, matched for adiposity, and of differing glycaemic status were compared using several insulin sensitivity indices and to also to assess insulin, glucose and insulin-like growth factor binding protein-1 (IGFBP-1) responses to intravenous glucose.MethodsSubjects with normal glucose tolerance (NGT; n = 24), impaired fasting glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 12), and type 2 diabetes (DM; n = 13) were recruited from Saudi (n = 33) and Caucasian (n = 28) populations. All had specimens taken in the context of a standard oral glucose tolerance test at their first visit and had the insulin sensitivity parameter (Si) determined by frequently-sampled intravenous glucose tolerance test (FSIVGTT) at a second visit.ResultsSaudis in the NGT and pooled glucose intolerance categories had significantly higher diastolic blood pressure (p < 0.001, p < 0.05 respectively) and HbA1c (p < 0.01, p < 0.05 respectively) compared to Caucasians. Caucasians in the NGT category had significantly higher Si, fasting and 2 h IGFBP-1 (p < 0.01, p < 0.05 and p < 0.01 respectively) compared to Saudis. Two hours following oral or intravenous glucose serum IGFBP-1 decreased to 44% (p < 0.001) and 50% (p < 0.05) of baseline levels respectively.ConclusionsOur data suggest that adult Saudis with normal glucose tolerance appear to be more insulin resistant than Caucasians matched for adiposity. In normal individuals at 2 h the IGFBP-1 level will be about half the baseline level regardless of the route of glucose administration.     

Aerobic training and L-arginine supplement attenuates myocardial infarction-induced kidney and liver injury in rats via reduced oxidative stress

IntroductionThe aim of the present study was to determine the effect of exercise training and l-arginine supplementation on kidney and liver injury in rats with myocardial infarction (MI).Material and methodsFour weeks after MI, 50 male wistar rats randomly divided into five followed groups: sham surgery without MI (Sham, n = 10), Sedentary-MI (Sed-MI, n = 10) 3: L-Arginine-MI (La-MI, n = 10) 4: Exercise training-MI (Ex-MI, n = 10) and 5: Exercise and L-arginine-MI (Ex + La-MI). Ex-MI and Ex + La-MI groups running on a treadmill for 10 weeks with moderate intensity. Rats in the L-arginine-treated groups drank water containing 4% L-arginine. Tissues oxidative stress and kidney and liver functional indices were measured after treatments.ResultUrea as a kidney function indexes, increased in Sed-MI group in compared to sham group and decreased significantly in Ex-MI and Ex + La-MI groups. The level of catalase (CAT) and glutathione stimulating hormone (GSH) of kidney were significantly lower in the MI-groups compared with the Sham group and kidney Malondialdehyde (MDA) levels increased after MI and significantly decreased in response to aerobic training and L-arginine. As well as, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as liver injury indices, increased in MI-groups and decreased by training and L-arginine. In this regards, liver MDA and CAT respectively increased and decreased in MI-groups, but aerobic training and L-arginine increased liver glutathione per-oxidase (GPx) and decreased liver MDA.ConclusionThese results demonstrated that kidney and liver function impaired 14 weeks after MI and aerobic training and L-arginine supplementation synergistically ameliorated kidneys and liver injury in myocardial infarction rats through oxidative stress reduction.     

Microscopic colitis patients have increased proportions of Ki67+ proliferating and CD45RO+ active/memory CD8+ and CD4+8+ mucosal T cells

BackgroundCollagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory bowel disorders of unknown etiology. This study investigated phenotypic characteristics of the mucosal lymphocytes in CC and LC.MethodsLamina propria and intraepithelial lymphocytes (LPLs, IELs) isolated from mucosal biopsies from CC (n = 7), LC (n = 6), as well as LC or CC patients in histopathological remission, (LC-HR) (n = 6) and CC-HR (n = 4) and non-inflamed controls (n = 10) were phenotypically characterized by four-color flow cytometry.ResultsThe proportions of CD8⁺ IELs were increased in CC and LC (p < 0.01) compared to controls. Increased proportions of CD45RO⁺CD8⁺ IELs and LPLs were observed in LC and even more in CC patients (p < 0.01). Both CC (p < 0.05) and LC patients had elevated proportions of CD4⁺8⁺ IELs and LPLs compared to controls. The proportions of CD45RO⁺ cells were increased in CD4⁺8⁺ IELs and LPLs (p < 0.05) in CC and LC patients compared to controls. Both CC (p < 0.05) and LC patients had higher proportions of Ki67⁺CD8⁺ IELs and LPLs compared to controls.In contrast, decreased proportions of CD4⁺ LPLs were observed in CC and LC as well as CD4⁺ IELs in LC compared to controls. Increased proportions of Ki67⁺CD4⁺ IELs and LPLs (p < 0.05) were observed in CC and LC patients.CC-HR but not LC-HR patients demonstrated normalized proportions of both IELs and LPLs compared to CC and LC patients respectively.ConclusionLC and CC patients have differences in mucosal lymphocyte subsets, with increased proportions of Ki67⁺ and CD45RO⁺ CD8⁺ and CD4⁺8⁺ mucosal T cells.     

PONI and its association with oxidative stress in type I and type II diabetes mellitus

ObjectiveParaoxonase (PON) is an antioxidant enzyme linked with cardiovascular disease (CVD), diabetes as it prevents LDL oxidation. The relation of PON with the other established risk factor of diabetic complications has not been looked into.Research design and methods370 subjects were included in the study. Dividing into four group, i.e. group I included type II DM (n = 220), group II was age matched control (n = 100), group III were type I DM (n = 25) and group IV (n = 25) were age matched control group. The protocol of the study was approved by the ethical committee of the institute. SOD, GSH, PON (paraoxonase and arylesterase activity), GHb, and MDA were estimated.ResultsA highly significant decrease in paraoxonase and arylesterase activity was seen in the type II DM (p < 0.0001) while in type I DM both the activity was not significant (p > 0.05). Paraoxonase and arylesterase activity of PONI showed a negative significant correlated with MDA (r = ?0.51, p < 0.0001 and r = ?0.23, p < 0.001) in type II DM but was not correlated in type I DM. The GHb and MDA levels were significantly increased (p < 0.0001) while the levels of SOD and GSH have been decreased in type I and type II DM.ConclusionPONI is definitely associated with development of the complications of diabetes. This may be due to the role of it as an antioxidant. As it also show a negative correlation with MDA like the other antioxidants studied.     

Effect of maternal use of flaxseed oil during pregnancy and lactation on glucose metabolism and pancreas histomorphometry of male offspring from diabetic rats

AimInvestigate if the maternal use of flaxseed oil prevents pancreatic alterations in the offspring of diabetic mothers.MethodsDiabetes was induced in female wistar rats (n = 12) by a high-fat diet and low-dose of streptozotocin. After the confirmation of the diabetes (glucose >300 mg/dL), rats were mated and once pregnancy was confirmed, they were allocated into three groups (n = 6): high-fat group (HFG); flaxseed oil group (FOG); and control group (CG) (nondiabetic rats). At weaning, male offspring (n = 12/group) received a standard chow diet. The animals were euthanized in two phases: at 100 and at 180 days, (n = 6/group). The pancreas was collected for histomorphometric and immunohistochemistry analysis.ResultsHFG showed hypertrophy of pancreatic islets at 100 and at 180 days (p < 0.0001), while the FOG offspring had islets with smaller diameters compared to HFG at both phases of sacrifice (p < 0.0001). HFG had a lower percentage of small islets when compared to CG and FOG, which had a higher percentage when compared to HFG (p = 0.0053) at 100 days. At 180 days HFG showed higher percentage of larger islets (p = 0.00137) and lower percentage of smaller islets (p = 0.00112), when compared to FOG. HFG showed lower islet insulin immunodensity at 100 days (p < 0.0001) and 180 days (p < 0.0001), whereas FOG was similar to CG (p < 0.0001) at 100 days and higher at 180 days (p < 0.0001).ConclusionsFlaxseed oil reduced the damage caused by maternal hyperglycemia, promoting normal pancreas histomorphometry and β cell mass.     

A new index predicts early allograft dysfunction following living donor liver transplantation: A propensity score analysis

Objective/AimThe aim of this study was to identify a new index to predict early allograft dysfunction following living donor liver transplantation.MethodsThe study enrolled 260 adult living donor liver transplantation recipients. Postoperative laboratory variables were assessed for their association with the prevalence of early allograft dysfunction using the inverse probability of treatment weighting and propensity-score matching (n = 93 pairs) analysis.ResultsForty-seven recipients (18.1%) developed early allograft dysfunction. In multivariable analysis, the alanine aminotransferase and gamma-glutamyl transpeptidase levels on postoperative day 1 were independent predictors of early allograft dysfunction. The alanine aminotransferase to gamma-glutamyl transpeptidase ratio (AGR) was developed. All cases were divided into two groups (Group 1 [AGR ≥ 8.47, n = 103] and Group 2 [AGR < 8.47, n = 157]). AGR ≥ 8.47 (OR 10.345, 95%CI 4.502–23.772, p < 0.001), hepatorenal syndrome (OR 3.016, 95%CI 1.119–8.125, p = 0.029), and graft to recipient weight ratio <0.8% (OR 2.155, 95%CI 1.004–4.624, p = 0.049) were independent risk factors for early allograft dysfunction. The prevalence of early allograft dysfunction was higher in group 1 (after adjusting for inverse probability of treatment weighting [n = 39; 37.9% vs n = 8; 5.1%] and propensity-score matching [n = 33; 35.5% vs n = 2; 2.2%]) than that in group 2 (p < 0.001).ConclusionsThe postoperative AGR is a practical index for predicting early allograft dysfunction after living donor liver transplantation.     

Functional polymorphisms of Toll-like receptors 2 and 4 alter the risk for colorectal carcinoma in Europeans

BackgroundColon carcinogenesis is associated with increased expression levels of Toll-like receptor 2 and Toll-like receptor 4.AimTo determine in a Caucasian population the role of Toll-like receptor 2 and Toll-like receptor 4 polymorphisms in colorectal cancer development.MethodsHospital based multicentre case control study involving 193 colorectal cancer patients and 278 healthy individuals. DNA samples were extracted from blood cells and genotyping of TLR2+597T>C, TLR2?4760T>C, TLR4?3745A>G, TLR2Arg753Gln, TLR4Asp299Gly was performed. Functionality of risk polymorphisms was evaluated through production of TNF-α in cell culture and Toll-like receptors levels quantified by real-time RT-PCR.ResultsTLR2+597CC homozygous had 5-fold decreased risk (odds ratio (OR) = 0.21, 95% CI: 0.09–0.50, p < 0.001) and TLR4 299Gly homozygous 3-fold increased risk of colorectal cancer (OR = 3.30, 95% CI: 1.18–9.28, p = 0.015). In stratified analysis, TLR2+597CC genotype protective effect was even higher in overweight individuals (OR = 0.17, 95% CI: 0.06–0.53, p < 0.001) and in never smokers (OR = 0.11, 95% CI: 0.02–0.51, p = 0.001). Also, the increased risk effect for TLR4 299Gly homozygous genotype was higher in overweight individuals (OR = 8.67, 95% CI: 1.11–87.85, p = 0.011). TLR2+597T>C polymorphism conferred 41% less (p = 0.03) and TLR4Asp299Gly 65% more TNF-α production (p = 0.02) with no differences in Toll-like receptors levels.ConclusionFunctional Toll-like receptor 2 and Toll-like receptor 4 polymorphisms significantly alter the risk to have colorectal cancer. Obesity and smoking may influence the risk for colorectal cancer in individuals presenting these genetic profiles.     

Group-based exercise combined with dual-task training improves gait but not vascular health in active older adults without dementia

BackgroundGait abnormalities and vascular disease risk factors are associated with cognitive impairment in aging.ObjectiveTo determine the impact of group-based exercise and dual-task training on gait and vascular health, in active community-dwelling older adults without dementia.MethodsParticipants [n = 44, mean (SD) age: 73.5 (7.2) years, 68% female] were randomized to either intervention (exercise + dual-task; EDT) or control (exercise only; EO). Each week, for 26 weeks, both groups accumulated 50 or 75 min of aerobic exercise from group-based classes and 45 min of beginner-level square stepping exercise (SSE). Participants accumulating only 50 min of aerobic exercise were instructed to participate in an additional 25 min each week outside of class. The EDT group also answered cognitively challenging questions while performing SSE (i.e., dual-task training). The effect of the interventions on gait and vascular health was compared between groups using linear mixed effects models.ResultsAt 26 weeks, the EDT group demonstrated increased dual-task (DT) gait velocity [difference between groups in mean change from baseline (95% CI): 0.29 m/s (0.16–0.43), p < 0.001], DT step length [5.72 cm (2.19–9.24), p = 0.002], and carotid intima-media thickness [0.10 mm (0.003–0.20), p = 0.04], as well as reduced DT stride time variability [8.31 coefficient of variation percentage points (−12.92 to −3.70), p < 0.001], when compared to the EO group.ConclusionsGroup-based exercise combined with dual-task training can improve DT gait characteristics in active older adults without dementia.     

Gender and ethnic differences in the prevalence of type 2 diabetes among Asian subgroups in California

AimsTo investigate gender and ethnic type 2 diabetes (DM) prevalences among California Asian subgroups versus other ethnic groups and if risk factors explain these differences.MethodsWe identified the prevalence of DM and associated risk factors, stratified by gender, among Chinese, Filipino, South Asian, Japanese, Korean, Vietnamese, Mexican, Other Hispanic, African-American, Caucasian, and Native American adults in a large survey conducted in 2009 (n = 46,091, projected n = 26.6 million).ResultsThe highest age-adjusted DM prevalence was seen in Native Americans (32.4%), Filipinos (15.8%), and Japanese (11.8%) among men and in Native Americans (16.0%) and African-Americans (13.3%) among women. Caucasian and Mexican men had higher DM prevalences than women. Age and risk factor-adjusted logistic regression showed DM more likely (relative to Caucasians) among women in Koreans (OR = 4.6, p < 0.01), Native Americans (OR = 3.0, p < 0.01), and Other Hispanics (OR 2.9, p < 0.01) and among men in Filipinos (OR = 7.0, p < 0.01), South Asians (OR = 4.7, p < 0.01), and Native Americans (OR = 4.7, p < 0.01). No specific risk factors accounted for the gender differences.ConclusionsEthnic and gender differences in DM prevalence persist, even after adjusting for lifestyle and other risk factors; prevalence is high among certain Asian American subgroups. Different diabetes prevention approaches may be needed across ethnic/gender groups.     

Effect of aerobic exercise on peripheral nerve functions of population with diabetic peripheral neuropathy in type 2 diabetes: A single blind,parallel group randomized controlled trial

ObjectiveTo evaluate the effect of moderate intensity aerobic exercise (40%–60% of Heart Rate Reserve (HRR)) on diabetic peripheral neuropathy.MethodsA parallel-group, randomized controlled trial was carried out in a tertiary health care setting, India. The study comprised of experimental (moderate intensity aerobic exercise and standard care) and control groups (standard care). Population with type 2 diabetes with clinical neuropathy, defined as a minimum score of seven on the Michigan Diabetic Neuropathy Score (MDNS), was randomly assigned to experimental and control groups by computer generated random number tables. RANOVA was used for data analysis (p < 0.05 was significant).ResultsA total of 87 patients with DPN were evaluated in the study. After randomization there were 47 patients in the control group and 40 patients in the experimental group. A comparison of two groups using RANOVA for anthropometric measures showed an insignificant change at eight weeks. For distal peroneal nerve’s conduction velocity there was a significant difference in two groups at eight weeks (p < 0.05), Degrees of freedom (Df) = 1, 62, F = 5.14, and p = 0.03. Sural sensory nerve at eight weeks showed a significant difference in two groups for conduction velocity, Df = 1, 60, F = 10.16, and p = 0.00. Significant differences in mean scores of MDNS were also observed in the two groups at eight weeks (p value significant < 0.05).ConclusionModerate intensity aerobic exercises can play a valuable role to disrupt the normal progression of DPN in type 2 diabetes.     

Efficacy and safety of combined pegylated interferon/ribavirin therapy in the management of rheumatological manifestations of chronic HCV patients

BackgroundThe hepatitis C virus (HCV) epidemic is particularly devastating in Egypt where its prevalence is about 12%. Chronic HCV infection can result in the accumulation of immune complexes and stimulate antibodies, which can result in extrahepatic manifestations (EHM).Aim of the workTo assess the efficacy and safety of combined pegylated interferon and ribavirin therapy in the management of rheumatological EHM in HCV patients.Patients and methodsTwenty-seven out of 50 consecutive HCV patients with rheumatologic EHM were eligible and included in this study. All patients included in this study were subjected to full history taking, clinical examination and laboratory investigations.ResultsThe mean age of the patients was 43.8 ± 7.6 years. The clinical response of the patients was: 2 patients (7.4%) were complete clinical responders, 5 (18.5%) were partial responders, 3 (11.1%) showed relapse and 17 (63%) were non-responders. There was a significant improvement in the number of patients with fatigue, polymerase chain reaction positivity and elevated liver enzymes (p < 0.0001, p < 0.0001, p = 0.03, p = 0.01 respectively). There was no significant correlation between virological and clinical responses. There was a significant correlation between virological and biochemical responses (p = 0.02). Minor side effects of the AVT developed in 13 (48.1%) patients: anemia (n = 5), mild thrombocytopenia (n = 8), flu-like symptoms (n = 7) and mild depression (n = 1).ConclusionPeg IFN and ribavirin did not improve HCV rheumatological extrahepatic manifestations. Antiviral treatment may also induce or worsen autoimmune disorders and is sometimes associated with major immune-mediated adverse events.     

Enteropathy associated T cell lymphoma in celiac disease: A large retrospective study

IntroductionPrognosis of enteropathy-associated T cell lymphoma is poor but predictors of survival remain ill-defined. How clinical presentation, pathological features and therapies influence outcome was evaluated in 37 thoroughly characterized patients with celiac disease and T-cell lymphoma.Patients and methodsMedical files were studied retrospectively. Lymphoma and intestinal mucosa were analysed by histopathology, multiplex PCR and intestinal intraepithelial lymphocytes phenotyping. Survival and prognostic factors were analysed using Kaplan–Meier curves with Logrank test and Cox Model.ResultsLymphoma complicated non clonal enteropathy, celiac disease (n = 15) and type I refractory celiac disease (n = 2) in 17 patients and clonal type II refractory celiac disease in 20 patients. Twenty-five patients underwent surgery with resection of the main tumour mass in 22 cases. In univariate analysis, non clonal celiac disease, serum albumin level > 21.6 g/L at diagnosis, chemotherapy and surgical resection predicted good survival (p = 0.0007, p < 0.0001, p < 0.0001, p < 0.0001, respectively). In multivariate analysis, serum albumin level > 21.6 g/L, chemotherapy and reductive surgery were all significantly associated with increased survival (p < 0.002, p < 0.03, p < 0.03, respectively).ConclusionsOur study underlines the prognostic value of celiac disease type in patients with T-cell lymphoma, and suggests that a combination of nutritional, chemotherapy and reductive surgery may improve survival.     

Cholesterol,non-cholesterol sterols and bile acids in paediatric gallstones

BackgroundDepending on underlying aetiopathogenetic factors human gallstones contain various amounts of cholesterol, non-cholesterol sterols and bile acids, which have remained unexplored in paediatric gallstone patients.AimsTo evaluate sterol and bile acids compositions of paediatric gallstones.Patients and methodsStudy group included 21 consecutively cholecystectomised children. Gas–liquid chromatography was used to quantitate gallstone sterols and bile acids. Results were compared to adult gallstones (n = 194).ResultsCholesterol stones (n = 9) had higher proportions of cholestenol and lathosterol, but lower those of lanosterol and phytosterols than pigment stones (n = 12) (p < 0.05 for each). Patients with gallstone cholesterol content over 70% were female. Gallstone cholesterol positively reflected body mass index and, in cholesterol stones-group, age (r = ∼+0.700, p < 0.05). Three patients on parenteral nutrition had brown pigment stones consisting of high amounts of campesterol and sitosterol ranging 483–9303 μg/100 mg of stone. Pigment stones had 13-fold higher amount of bile acids than cholesterol stones (p < 0.05). Black pigment stones contained ∼3-fold higher phytosterol proportions, and pigment stones and cholesterol stones had ∼43% lower proportions of deoxycholic acid than adults (p < 0.05).ConclusionGallstones in patients on parenteral nutrition are rich in phytosterols. With respect to gallstone sterols, gallstone disease of adolescent girls resembles that of adults. Composition of bile acids in paediatric gallstones is different from adults.     

Prognostic factors in patients with non resectable metastatic colorectal cancer in the era of targeted biotherapies: Relevance of Köhne's risk classification

BackgroundKöhne's prognostic classification has been previously proposed, based on performance status, alkaline phosphatase level, number of metastatic sites and white blood cells count.AimsTo identify prognostic factors for survival and to assess the validity of Köhne's classification, in the era of targeted biotherapies, in patients treated with chemotherapy for non resectable metastatic colorectal cancer.MethodsA total of 290 consecutive patients were retrospectively identified in all gastroenterology units of one French county, between 2004 and 2008. Univariate and multivariate analysis for overall survival were performed using pre-treatment patient characteristics.ResultsAll data were available for prognostic categorization in 133 patients. Median survival was 22.1 months. The distribution and median survival for Köhne's prognostic groups were as following: good (n = 73; 24.8 months), intermediate (n = 35; 24.2 months), and poor (n = 25; 7.0 months). The survival difference was significant between good and poor prognostic groups (p < 0.01) and between intermediate and poor prognostic groups (p < 0.01), but not between good and intermediate prognostic groups (p = 0.5). The two independent prognostic factors of survival in multivariate analysis were performance status 0/1 (p < 0.01) and white blood cells count < 10 × 10⁹/L (p < 0.01).ConclusionsThe relevance of Köhne's classification is questioned. A simplified score could be validated by largest studies, based on white blood cells count and performance status.     

Antioxidant effect of p-coumaric acid on interleukin 1-β and tumor necrosis factor-α in rats with renal ischemic reperfusion

Background and aimsRenal ischemia-reperfusion occurs in some clinical conditions such as kidney surgery that can leads to acute renal failure. The aim of this study was to investigate the effect of p-coumaric acid (CA) on ischemia reperfusion (I/R) injury.MethodsThirty rats were randomly divided into five groups; control, CA (100 mg/kg), I/R, propylene glycol (10%) + I/R and CA + I/R, (n = 6 each). CA and propylene glycol were administered orally for 2 weeks. Then, the rats were subjected to bilateral renal ischemia for 45 min and followed by reperfusion for 24 h. All rats were killed and kidney function tests, tissue malondialdehyde and activity of antioxidant enzymes were determined. Histopathological evaluations were also performed. In addition, renal expression of the tumor necrosis factor-α and interleukin-1β were determined using enzyme-linked immunosorbent assay and immunohistochemistry.ResultsCA significantly improved the Cr and BUN levels in CA + I/R group compared to I/R group (p < 0.005 and p < 0.001, respectively). Reduction of tissue superoxide dismutase, glutathione peroxidase and catalase, were significantly improved by CA (p < 0.01, p < 0.01 and p < 0.05). Treatment with CA also resulted in significant reduction in tissue MDA (p < 0.05), TNF-α (p < 0.001) and interleukin-1β expression (p < 0.001) that were increased by renal I/R. Also, the rats treated with CA had nearly normal structure of the kidney.ConclusionsThe present findings suggest that, CA protects the kidneys against I/R injury via its antioxidant and anti-inflammatory effects.     

Diabetes care in Ireland: A survey of general practitioners

AimTo investigate the organisation of diabetes care in general practice in Ireland and identify areas for future development.MethodsSurvey of a representative sample of 600 general practitioners (GPs). The questionnaire contained closed and open-ended questions addressing 4 topics; characteristics of the practice, diabetes care delivery, use of services and opportunities for developing diabetes care.ResultsThe response rate was 44% (n = 262). There were an additional 86 responses to a follow-up shortened version of the survey resulting in a 58% response rate for 9 key questions. The majority of respondents were from an urban (43%, n = 112) or a mixed area (39%, n = 101) and 19% of practices were single-handed (n = 66). The reported prevalence in participating practices was 0.7% for Type 1 diabetes and 2.8% for Type 2 diabetes. Forty-five percent of GPs maintained a diabetes register (n = 157) while 53% reported using guidelines (n = 140). A formal call recall system was reported by 30% (n = 78) with a further 20% (n = 54) reporting a regular if informal approach to calling patients for review. With regard to the use of diabetes related services 63% reported direct access to a dietician (n = 165), 57% direct access to chiropody services (n = 149) and 89% had direct access to retinopathy screening (n = 234). There was a significant association between maintaining a diabetes register and other aspects of care delivery such as engaging in formal recall (p < 0.001), using guidelines (p < 0.001) and a declared special interest in diabetes (p = 0.001). Of a number of choices 75% of GPs thought that training was the principal opportunity for improving diabetes care. In response to the open-ended questions GPs cited lack of resources, time constraints and workload as barriers to effective care delivery.ConclusionsDelivery of diabetes care in Ireland remains largely unstructured. Key challenges to improving diabetes care appear to extend to the system and organisational level of care delivery.