Topical tacrolimus 0.1% ointment for treatment of cutaneous Crohn's Disease

Peer reviewedPublisher PD

Detection of Campylobacter concisus and other Campylobacter species in colonic biopsies from adults with ulcerative colitis

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The effect of Helicobacter pylori infection on gastric acid secretion in man

Helicobacter pylori (H pylori) infection is the commonest chronic bacterial infection world-wide. The work carried out in this thesis has sought to explore the effect of the infection on gastric secretory function in man. We developed a new test of gastric acid secretion using the substance gastrin releasing peptide (GRP) as the stimulus. Acid secretion measured in response to intravenous infusion of GRP reflects the combined functional response of the antrum and body of the stomach. It activates both stimulatory and inhibitory controls of acid secretion and in these respects it simulates the response to eating. The reproducibility of the GRP test was assessed and was found to be high for both gastrin and acid secretion. Using this new tool we studied acid secretion in a variety of subjects with and without H pylori infection. We have found that GRP stimulated acid secretion is increased six fold in DU patients with the infection compared to H pylori negative healthy volunteers (true normals). This exaggerated acid response is likely to represent a key pathophysiological defect which underlies DU disease. We have demonstrated for the first time that eradication of H pylori infection leads to normalisation of basal and GRP stimulated acid secretion in DU patients. These novel findings have shed considerable light on the understanding of the pathophysiology of DU disease and the role of H pylori infection in it. We have also shown for the first time that GRP stimulated acid secretion is increased two to three fold in H pylori positive healthy volunteers compared to true normals. This secretory abnormality also fully resolves following eradication of the infection. Since half the world's population is colonised with H pylori, it is essential that all future gastric secretory studies ensure that their control subjects are negative for the infection. The presence of the secretory abnormality in healthy volunteers may also be of relevance to other upper Gl diseases such as reflux disease. We proceeded to investigate the mechanism of the exaggerated acid response to GRP in DU patients and presented evidence compatible with this being due to impaired inhibitory control of acid secretion. We proceeded to examine the effect of the most commonly prescribed medication for dyspepsia, i.e. ranitidine, on acid secretion in healthy volunteers with and without H pylori infection. We showed that a two month course of ranitidine leads to a doubling of basal acid output and a 68% increase in GRP stimulated acid output two days after withdrawing treatment. This rebound acid hypersecretion is not associated with any significant change in gastrin concentrations and fully resolves within ten days of stopping ranitidine. These findings may offer an explanation for the common clinical problem of rapid resurgence of dyspeptic symptoms following discontinuation of acid suppressive therapy. Finally, we used the GRP test to study acid secretion in patients with non ulcer dyspepsia (NUD) and H pylori infection. We showed that a significant proportion of NUD patients had an exaggerated acid response to GRP similar to DU patients i.e. they displayed the DU diathesis. This raises the exciting possibility that this group of NUD patients may also be cured by eradication of their H pylori infection

Lack of association between the rs2294008 polymorphism in the prostate stem cell antigen gene and colorectal neoplasia : a case-control and immunohistochemical study

PMID: 22824379 [PubMed - indexed for MEDLINE] PMCID: PMC3500224 Free PMC ArticlePeer reviewedPublisher PD

Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori

Background & Aims:Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric atrophy and hypochlorhydria. First-degree relatives of patients with gastric cancer have an increased risk of developing gastric cancer. The aim of this study was to determine the prevalence of atrophy and hypochlorhydria and their association with H. pylori infection in first-degree relatives of patients with gastric cancer. Methods:H. pylori status, gastric secretory function, and gastric histology were studied in 100 first-degree relatives of patients with noncardia gastric cancer and compared with those of controls with no family history of this cancer. Results: Compared with healthy controls, relatives of patients with gastric cancer had a higher prevalence of hypochlorhydria (27% vs. 3%) but a similar prevalence of H. pylori infection (63% vs. 64%). Relatives of cancer patients also had a higher prevalence of atrophy (34%) than patients with nonulcer dyspepsia (5%) matched for H. pylori prevalence. Among the relatives of cancer patients, the prevalence of atrophy and hypochlorhydria was increased only in those with evidence of H. pylori infection, was greater in relatives of patients with familial cancer than in relatives of sporadic cancer index patients, and increased with age. Eradication of H. pylori infection produced resolution of the gastric inflammation in each subject and resolution of hypochlorhydria and atrophy in 50% of the subjects. Conclusions: Relatives of patients with gastric cancer have an increased prevalence of precancerous gastric abnormalities, but this increase is confined to those with H. pylori infection. Consequently, prophylactic eradication of the infection should be offered to such subjects

Gut mucosal microbiome signatures of colorectal cancer differ according to BMI status

ACKNOWLEDGMENTS We gratefully acknowledge the NHS Grampian Biorepository for providing access to CRC patient samples and data. We thank members of the GI Research Team for discussions and advice. The authors thank Brennan Martin and the Centre for Genome Enabled Biology and Medicine for useful discussions.Peer reviewedPublisher PD

The TLR4 D299G and T399I SNPs Are Constitutively Active to Up-Regulate Expression of Trif-Dependent Genes

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Geological and Geotechnical Assessment of Gabal Ataqa Dolostones, for Pavement Construction in Egypt

Aggregate is a collective term for the mineral materials such as sand, gravel and crushed stone. By weight, aggregate generally occupies about 92-96 percent of the hot mix asphalt (HMA), and about 79-85 percent of the Portland cement concrete (PCC). Aggregate is also used for Base and Sub-base courses for both flexible and rigid pavements. This research aims to investigate the geological and geotechnical properties of Gabal Ataqa dolostone for pavement construction projects in Egypt. A total of six dolomite microfacies were recognized and classified according to the dolomite rock classification. The X-Ray Diffraction (XRD) analysis showed that Ataqa dolostones consist mainly of dolomite (89.79%) and calcite (7.74%), while quartz (2.3 %) and halite (0.18 %) were found in small amounts in some samples. Generally Ataqa dolostone is around stoichiometric (50.96%), and may belong to dolomite of late diagentic coarse crystalline dolomite. The chemical investigation showed that the major elements of the investigated dolostone rocks are SiO2 (1.72 %); CaO (32.03%), MgO (19.18%), Fe2O3 (0.22 %), Na2O (0.11%), and Al2O3 (0.05%) while the loss on ignition is about (46.19 %.). The trace elements consist of strontium (116 ppm), barium (14.0 ppm); and very low amount of zirconium (3 ppm). Petrographic, chemical, mineralogical, and compressive strength of Ataqa dolostone rocks beside, geotechnical properties of the produced coarse aggregates were investigated. Los Angeles abrasion, apparent specific gravity, water absorption, disintegration, and stripping were evaluated. The results of the conducted testing indicate that Ataqa dolostone rocks are suitable for road construction and concrete industry.

Adaptive response of neonatal sepsis-derived Group B Streptococcus to bilirubin

This work was funded by the Neonatal Unit Endowment Fund, Aberdeen Maternity Hospital. RH is funded by a career researcher fellowship from NHS Research Scotland. SG was funded by the MRC Flagship PhD programme. We are grateful for the support of Dr Phil Cash and Aberdeen Proteomics, at University of Aberdeen, in completing this project. Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-24811-3.Peer reviewedPublisher PD

Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do no