Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

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Calcium malabsorption, hypocalcemia and skeletal demineralization are well-recognized features of untreated celiac disease. This study investigates calcium absorption and bone mineral density (BMD) after a prolonged, over 4 years, treatment with a gluten-free diet. Twenty-four adult females with treated celiac disease and twenty age- and sex-matched control subjects were studied. Mean body mass index (MBI), energy intake, serum calcium, and serum 25(OH)D concentrations in treated celiacs did not differ from controls. However, while both dietary calcium and protein intake were significantly higher in celiacs (P<0.012), fractional calcium absorption was lower (mean percentage+/-SD; treated 39.8+/-12 versus controls 52.3+/-10, P<0.001). Thus, after adjusting for calcium intake, the estimated amount of calcium absorbed daily was similar in both groups. Whole body, spine and trochanter BMD were significantly lower in treated celiac patients compared with controls (P<0.05). There were significant inverse correlations between: serum parathyroid hormone (PTH) and femoral neck or total body BMD (P<0.01), PTH and duration of gluten-free diet (P=0.05), and fractional calcium absorption and alkaline phosphatase (P=0.022). Increased calcium intake could potentially compensate for the reduced fractional calcium absorption in treated adult celiac patients, but may not normalize the BMD. In addition, the inverse correlation between PTH and time following treatment is suggestive of a continuing long-term benefit of gluten withdrawal on bone metabolism in celiac patients.

Disease phenotype in CD and disease extent in UC appeared to be genetically influenced. Smoking is a risk factor for CD but is protective for UC. Early exposure to "infections" during childhood may be associated with the development of IBD.

Background: colonic polypectomy reduces the subsequent rate of development of colonic cancer but is not without its risks. We aimed to examine our complication rates in relation to the characteristics of polyps and techniques employed. Methods: a database for all colonic polypectomies performed over a 3½-year period between 2006 and 2009 was matched against all patients readmitted after an endoscopy. serious complications post-polypectomy were defined as events leading to readmission within 14 days. Results: We performed 2106 polypectomies on 1252 patients in this period. Fourteen patients or 24 (1.1%) polypectomies experienced complications. Two patients (0.09%) experienced perforation, 10 (0.47%) had bleeding and 3 (0.14%) had post-polypectomy syndromes. Our bleeding rate was 1:211, lower than the national standard of 1:100. No deaths were reported. complication rates rose from 1% in the smallest group (1-10 mm) to 4.9% in the largest (>31 mm) but the difference was not statistically significant (p=0.067). Right-colon polypectomies had a higher tendency of developing post-polypectomy syndrome and bleeding (p=0.002). complication rates in snare polypectomies were not significantly different from that of hot biopsies (p=0.64). however, endoscopic mucosal resections (eMR) had significantly more complications compared to snares (p=0.045) and hot biopsies (p=0.026). Conclusion:We achieved lower bleeding rates than that published nationally. hot biopsies did not carry a higher risk unlike eMRs. although polyp size may be an important risk factor, statistical significance was not met. ascending and transverse colon polypectomies carried the highest risks of complications.

tended to be higher (P = 0.07). In the placebo group, the difference in heart rate at high altitude was positively correlated with maximum headache scores (r = 0.8, P < 0.01) and inversely related to saturation values 3 hours after arrival at high altitude (r = -0.8, P < 0.01; figure). CommentThe incidence of headache at high altitude increases when arterial oxygen saturation and associated oxygen partial pressure decline with increasing altitude.2 In this study, however, aspirin prevented headache without improving oxygenation. Pretreatment with aspirin raised the headache threshold, which was indicated by toleration of lower saturation values. Moreover, intake of aspirin was associated with less pronounced cardiorespiratory responses to short term exercise at high altitude. Since acute hypoxia augments prostaglandin concentrations, 3 and prostaglandins increase ergoreceptor activation and accompanying sympathetic stimulation, 4 aspirin probably prevents headache by diminishing these responses. Prostaglandins also enhance nociception, and reduced hyperalgesia may therefore have contributed additionally to the prophylactic efficacy of aspirin. Nevertheless, within the first few days of exposure to high altitude, symptoms of acute mountain sickness usually disappear even without drugs. Simultaneously, sympathetic responsiveness decreases due to desensitisation of adrenoceptors, 5 again indicating some relation between sympathetic activity and development of headaches at high altitude. If this relation is true, aspirin may support adaptation to high altitude by reducing sympathetic activity mediated by prostaglandins.Contributors: MB designed the study, examined the subjects, did exercise testing, performed the statistical analysis and took various measurements. RL did the headache scoring and supervised the health of the subjects. WN undertook the randomisation, distribution of tablets, control of data and statistics. MP took various measurements (blood sampling)and did exercise testing.

The aim of our study was to audit dysphagia referrals received by a specialist gastroenterology unit during an entire year. We used a prospective audit carried out over a 12-month period at the District General Hospital gastroenterology unit. The audit included 396 consecutive patients who were referred with swallowing difficulties. We found that 60 referrals (15.2%) were inaccurate and the patients had no swallowing problem. Of the 336 patients with genuine dysphagia, only 29 (8.6%) were new cancer cases. The large majority of subjects had benign disease mostly related to acid reflux. Weight loss was significantly associated with malignancy but also occurred in one third of patients with reflux alone. The temporal pattern of dysphagia was not significantly predictive of cancer. All the cancer patients were above the age of 50 years. Although patients were in general assessed rapidly after hospital referral, the productivity, in terms of early tumor diagnosis, was extremely low. We conclude that there is a substantial rate of inaccurate referrals of dysphagia patients. Most true cases of swallowing difficulty relate to benign disease. Even the devotion of considerable resources to the early diagnosis of esophago gastric malignancy in an attempt to conform with best practice guidelines results in a very low success rate in terms of the detection of potentially curable tumors.

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