Search

Acute upper gastrointestinal bleed (AUGIB) is one of the most common medical emergencies in the UK, with roughly one presentation every 6 min. Despite advances in therapeutics and endoscopy provision, mortality following AUGIB over the last two decades has remained high, with over 9,000 deaths annually in the UK; consequently, several national bodies have published UK-relevant guidelines. Despite this, the 2015 UK National Confidential Enquiry into Patient Outcome and Death in AUGIB highlighted variations in practice, raised concerns regarding suboptimal patient care and released a series of recommendations. This review paper incorporates the latest available evidence and UK-relevant guidelines to summarise the optimal pre-endoscopic, endoscopic, and post-endoscopic approach to and management of non-variceal and variceal AUGIB that will be of practical value to both general physicians and gastroenterologists.

The effect of acetaminophen on sulfamethazine N-acetylation by human N-acetyltrasferase-2 (NAT2) was studied in 19 (n = 19) healthy male volunteers in two different phases. In the first phase of the study the volunteers were given an oral dose of sulfamethazine 500 mg alone and blood and urine samples were collected. After the 10-day washout period the same selected volunteers were again administered sulfamethazine 500 mg along with 1000 mg acetaminophen. The acetylation of sulfamethazine by human NAT2 in both phases with and without acetaminophen was determined by HPLC to establish their respective phenotypes. In conclusion obtained statistics of present study revealed that acetaminophen significantly (P<0.0001) decreased sulfamethazine acetylation in plasma of both slow and fast acetylator male volunteers. A highly significant (P<0.0001) decrease in plasma-free and total sulfamethazine concentration was also observed when acetaminophen was co-administered. Urine acetylation status in both phases of the study was found not to be in complete concordance with that of plasma. Acetaminophen significantly (P<0.0001) increased the acetyl, free and total sulfamethazine concentration in urine of both slow and fast acetylators. Urine acetylation analysis has not been found to be a suitable approach for phenotypic studies.

Sudan-1 has been used for coloring food. However, recent alarms worldwide about the carcinogenic and mutagenic properties of azo-compounds have led to concerns over their human consumption. In the U.K. in 2005, over 570 products were found to be contaminated with the azo dye Sudan-1 and this and the health risks associated with this dye resulted in the subsequent international ban of this additive in all foodstuff, at all levels, relating to human consumption. These incidents have also necessitated the need for high throughput low cost reliable approaches for the detection and quantification of food contaminated by such azo compounds. While there are a small number of analytical techniques that can be considered portable, many lack sensitivity. By contrast, we show that employing a portable Raman spectrometer, using surface enhanced Raman scattering (SERS), can provide good sensitivity, such that Sudan-1 can be quantified in a complex food matrix reliably over the range of 10−3to 10−4mol L−1. We also demonstrate that a variety of multivariate approaches including principal components analysis (PCA), partial least-squares (PLS) regression, artificial neural networks (ANNs), and support vector regression (SVR) can be employed for the chemical analysis of this dye in a quantitative manner. Compared to the commonly used univariate approaches, where the area under a single band in assessed, the advantage of using multivariate approaches is that these algorithms can analyze the full spectra directly and the laborious task of selecting and integrating marker appropriate quantitative spectral bands can be avoided thus greatly simplifying and speeding up data analysis.

Monitoring enzyme kinetics is an important aspect of biochemistry and is essential when studying metabolism. In this study we demonstrate that succinate dehydrogenase activity of mitochondria can be analyzed quantitatively by surface enhanced Raman scattering (SERS). We used the artificial electron acceptor reporter molecule 2,6-dichlorophenolindophenol (DCPIP) that when oxidized is SERS active. On reduction this redox dye changes from blue to colorless and is SERS inactive. This color change allows UV/vis spectrophotometry to be used as a standard reference measurement as well as SERS. SERS analysis incorporated kinetic time course measurements and employed a portable laser Raman spectrometer using an excitation wavelength of 785 nm in conjunction with gold colloids. Good correlation coefficients and quantitative data were observed with the additional advantage that analysis by SERS also provided good fingerprint spectral information from vibrational band frequencies thus allowing the potential of multiplexing enzyme reactions. We believe that this is the first demonstration of monitoring succinate dehydrogenase activity with SERS and that SERS has considerable potential for being applied to the analysis of metabolic processes.

The viability of the application of surface-enhanced resonance Raman spectroscopy (SERRS) to the quantitative analysis of the dye alcian blue 8GX has been examined with the use of citrate- and borohydride-reduced silver colloids. A good linear correlation is observed for the dependence of the SERRS signal intensities at 1344 and 1536 cm−1(R =0.992 and 0.994, respectively) on dye concentrations in the range of 10−9–10−7M, when using the citrate-reduced silver sol. Likewise, a good linear correlation is also observed for the dependence of the SERRS signal intensities at 1344 and 1536 cm−1(R =0.978 and 0.959, respectively) on dye concentrations in the range 10−10–10−9M, when using the borohydride-reduced silver sol. At concentrations of dye above 10−7M, the concentration dependence of the SERRS signals is nonlinear, almost certainly due to the coverage of the surface of the colloidal silver particles by the dye being in excess of a full monolayer. However, at concentrations of alcian blue greater than 10−7M, resonance Raman spectroscopy (RRS) can be employed for quantitative analysis of the dye. When performing RRS, using methanol as an internal standard, we observed a good linear correlation for the dependence of the signal intensities at 1344 and 1536 cm−1(R =0.995 for both bands) on the dye concentration in the 10−6–10−3M range. The limits of detection of alcian blue by SERRS using a citrate-reduced silver sol, SERRS using a borohydride-reduced silver sol, RRS, and visible absorption spectroscopy are found to be 26 ppb, 203 ppt, 2 ppm, and 0.7 ppm, respectively.

Rare-earth ions can easily be incorporated into fluoride glasses in moderate to large concentrations. Because these glasses possess low fundamental frequencies, they appear to have many advantages over oxide glasses as hosts for rare-earth ions used in optical amplifiers and lasers. We have investigated the optical properties (fluorescence, absorption, and excited-state lifetimes) of AlF_3-based glass doped with Pr^3+, Yb^3+, and Lu^3+. The effects of different dopant levels on the optical properties of this glass system have also been investigated. These results are compared to those obtained for the same ions in other glass hosts.

Not Available

Not Available

Not Available

Not Available

New AlF3-based glasses with enhanced thermal stability have been synthesized and characterized using differential scanning calorimetry, spectroscopic and viscosity measurements. The Hgvalues for these new glasses compare favorably with those of the base glass ((mol%) 30.2AlF3-10.6BaF2-20.2CaF2-8.3YF3-3.5MgF2-3.8NaF-13.2SrF2-10.2ZrF4), ZBLAN and other compositions of halide glasses. Core and cladding glasses were synthesized using these compositions and evaluated for fiber drawing.

Rare-earth ions can easily be incorporated into fluoride glasses in moderate to large concentrations. Because these glasses possess low fundamental frequencies, they appear to have many advantages over oxide glasses as hosts for rare-earth ions used in optical amplifiers and lasers. We have investigated the optical properties (fluorescence, absorption, and excited-state lifetimes) of AlF_3-based glass doped with Pr^3+, Yb^3+ and Lu^3+. The effects of different dopant levels on the optical properties of this glass system have also been investigated. These results are compared to those obtained for the same ions in other glass hosts.

1. Polyethylene glycol has been used extensively as a probe to measure passive small-intestinal permeability in viro. However, there has been some uncertainty as to its suitability for use as an indicator of the permeation of water-soluble molecules across the intestinal wall because it seems to traverse the mucosa in much greater quantities than sugar molecules of equivalent Mr. 2. We have measured the permeation of polyethylene glycol-400 and lactulose from aqueous solution across pure lipid solvents in vitro. We found considerable transport of polyethylene glycol-400 across chloroform (1.03 g h−1 m−2) but no movement across petroleum ether. 3. However, in a separate experiment in which phospholipid (egg lecithin) was dissolved in the petroleum ether, permeation of polyethylene glycol-400 did occur (0.13 g h−1 m2), implying interaction of polyethylene glycol-400 with the phospholipid. No permeation of lactulose was seen in any of the experiments. 4. Our results suggest that, because of its interaction with lipid solvents, polyethylene glycol-400 is unsuitable as a probe to measure passive intestinal permeability in vivo.

A genetic polymorphism is responsible for determining that some humans express lactase at high levels throughout their lives and are thus lactose tolerant, while others lose lactase expression during childhood and are lactose intolerant. We have previously shown that this polymorphism is controlled by an element or elements which act in cis to the lactase gene. We have also reported that 7 polymorphisms in the lactase gene are highly associated and lead to only 3 common haplotypes (A, B and C) in individuals of European extraction. Here we report the frequencies of these polymorphisms in Caucasians from north and south Europe and also from the Indian sub-continent, and show that the alleles differ in frequency, the B and C haplotypes being much more common in southern Europe and India. Allelic association studies with lactase persistence and non-persistence phenotypes show suggestive evidence of association of lactase persistence with certain alleles. This association was rather more clear in the analysis of small families, where haplotypes could be determined. Furthermore haplotype and RNA transcript analysis of 11 unrelated lactase persistent individuals shows that the persistence (highly expressed) allele is almost always on the A haplotype background. Non-persistence is found on a variety of haplotypes including A. Thus it appears that lactase persistence arose more recently than the DNA marker polymorphisms used here to define the main Caucasian haplotypes, possibly as a single mutation on the A haplotype background. The high frequency of the A haplotype in northern Europeans is consistent with the high frequency of lactase persistence.

Unclad, low-loss AlF_3-based glass fibers with enhanced chemical durability have been successfully used for the first time to our knowledge as intrinsic evanescent infrared sensors for monitoring liquid chemicals. Different liquids with absorption bands between 1 and 4.5 μm, such as alcohol, acetonitrile, and mixtures of alcohol/acetonitrile and water/acetonitrile, have been tested. These fibers have also been used successfully as distributed sensors for simultaneous monitoring of different chemical species.

The green energy production through water splitting under visible light irradiation has become an emerging challenge in the 21st century. Photocatalysis, being a cost-competitive and efficient technique, has grabbed much more attention for environmental applications, especially for hydrogen evolution. In this article, the hybrid Cu3V2O8-WO3 nanostructures were prepared through the hydrothermal method by using copper acetate, ammonium metavanadate, and Na2WO4 · 2H2O as precursors. The varying contents of Cu3V2O8 in WO3 were 0.2%, 0.5%, 1.0%, 2.0%, and 3.0%. The X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET), UV-Vis, and photoluminescence (PL) emission spectroscopy were used to investigate the structural, morphological, surface area, and optical properties of prepared samples. The average crystalline size of the pure WO3 ranges from 10 to 15 nm and 70 to 195 nm for an optimal composite sample. The structural phase of the hybrid WO3-Cu3V2O8 nanoparticles was found to transfer from monoclinic to hexagonal by incorporating the Cu3V2O8 contents. The enhanced photocatalytic performance for hydrogen evolution was observed for 2% Cu3V2O8-WO3 composite sample. The key to this enhancement lies at the heterojunction interface, where charge separation occurs. In addition, the excellent photocatalytic activity was attributed to a higher surface area, efficient charge separation, and extended visible light absorption. This work provides an in-depth understanding of efficient separation of charge carriers and transfer processes and steer charge flow for efficient solar-to-chemical energy applications.

IntroductionTuberculosis (TB) carries significant morbidity. It is most commonly pulmonary but it can also affect the gastrointestinal (GI) tract (6% of total cases in UK). Abdominal tuberculosis (A-TB) is a rare disease which can present a unique diagnostic challenge mimicking various GI diseases. We reviewed a 10 year cumulative regional TB database to report results on this unusual condition.MethodA retrospective review of patients diagnosed with A-TB between 2006 & 2016 in a single tertiary centre in South Birmingham covering a multi-ethnic urban population of ~7 50 000. A central surveillance database managed by Respiratory Physicians and Public Health England was used to identify patients with A-TB. We reviewed clinical data from electronic records including radiology, chemical pathology, histopathology, endoscopy databases, surgical notes and letters.ResultsOf 41 patients [M=22 (54%);mean age 42y (SD ±17y)] identified with A-TB, 17 (41%) were Pakistani, 6 (15%) were other Asian and 8 (19%) were Afro-Caribbean with no data on country of origin or ethnicity recorded for the remainder. Thirty three (80%) were residents of economically deprived areas of Birmingham which were among the 10% of most deprived constituencies in UK, with an overall lowest national decile of 1#.(#Index of multiple deprivation as per local council)The most frequently reported symptoms were abdominal pain (n=23; 56%), weight loss (n=17; 41%), fever (n=10; 24%) and vomiting (n=9; 22%). Twelve (29%) patients were first seen in the surgical clinic and 9 (22%) in a medical gastroenterology clinic. A-TB was confirmed on tissue biopsy in 24 (58%) of which 2 were post-bowel resection. Seventeen (41%) patients had positive cultures with full drug sensitivity and only 5 (12%) patients had polymerase chain reaction (PCR) tests. Eight patients (20%) had concurrent pulmonary TB. Thirty seven patients (90%) received full, successful treatment for A-TB.ConclusionAsian ethnicity and low socioeconomic status appear to be risk factors for A-TB in a single tertiary centre. Histological diagnosis at endoscopic or surgical biopsy is a reliable diagnostic tool for confirming TB. Both gastroenterologists and surgeons need to consider A-TB in their differentials, as once diagnosed, most are successfully treated.Disclosure of InterestNone Declared

IntroductionA Cancer Research UK report1suggests GI endoscopy demand will increase dramatically, with a 45% increase over 5 years. We compare regional data to national projections, to provide reliable regional estimates to guide capacity planning.MethodJAG mandates the routine data submission from all hospital/Trust sites. This included adult OGD and colonoscopy procedure counts at University Hospital Birmingham and Heart of England NHS Trusts, comprising 4 hospital centres.Results201020112012201320142015OGD (n)13 720 13 510 13 646 14 351 14 727 17 545 % increase on 2010- −1.53 −0.54 4.60 7.34 27.88 % change on prior year- −1.53 1.01 5.17 2.62 19.13 % change from 2013- - - - - 22.3 Colonoscopy (n)7853 8269 9002 9431 9745 10 411 % increase on 2010- 5.30 14.63 20.09 24.09 32.57 % change on prior year- 5.30 8.86 4.77 3.33 6.83 % change from 2013- - - - - 10.4 Flexible Sigmoidoscopy (n)5419 5449 5921 5979 5966 6173 % increase on 2010- 0.55 9.26 10.33 10.09 13.91 % change on prior year- 0.55 8.66 0.98 −0.22 3.47 % change from 2013- - - - - 3.2 Above predicted increases in OGD procedures were observed, with 27.8% growth over 5 years. (22% increase over two years was higher than predicted over five).Colonoscopy growth was consistent with national projections at 32.6% growth in 5 years (10% increase over 2 years, consistent with national estimates). Bowel cancer screening lists occur at both Trusts.Flexible sigmoidoscopy growth varied between Trusts (17.1% since 2013 at UHB, 3.3% reduction at HEFT). Bowel scope, although established at UHB is not yet at HEFT, was fundamental to projections.ConclusionThese data demonstrate large recent growth in endoscopy conducted in South/East Birmingham for OGD and colonoscopy, with greater than predicted growth in the former. Given current challenges of limited endoscopy rooms and staff retention, urgent capacity planning is required in this area and likely across the Midlands.Reference. Brown H, Wyatt S, Croft S, Gale N, Turner A, Mulla A. Scoping the Future, An evaluation of endoscopy capacity across the NHS in England. Cancer Research UK, Sept 2015Disclosure of InterestNone Declared

IntroductionIron deficiency is a common extra-intestinal complication of IBD and, as large doses of intestinal iron are poorly tolerated by patients with IBD [1] intravenous iron supplementation is often recommended [2]. It is also often stated that, in patients with chronic systemic inflammation, iron is poorly absorbed from the gut. This has been sparsely investigated although we have previously shown that patients with elevated CRP tend to absorb ferrous sulphate less well [3]. The hepatic peptide hepcidin is the master iron regulator. It is not known if hepcidin prevents iron uptake from the gut in practice in anaemic IBD patients.MethodWe measured serum hepcidin (using MALDI TOF mass spectrometry) in serum samples stored from a previously published phase III trial using ferric maltol to treat IBD patients with anaemia [4]. We then analysed data from this study retrospectively to assess whether baseline hepcidin or CRP would predict response to oral iron supplementation.ResultsThe table below gives the baseline characteristics of the study cohort: Mean SD Haemoglobin 110 g/L 103 Ferritin 8.6 ug/L 6.77 TSAT 10.6% 11.69 CRP 5.09 mg/L 7.225 Hepcidin 30 ng/ul 12 There was no correlation at baseline between CRP and hepcidin. Baseline hepcidin was not associated with response to iron replacement either at the primary endpoint (week 12) or at one year follow up. Neither CRP nor hepcidin was associated with haemoglobin response. However week 12 ferritin was inversely correlated to baseline CRP (p=0.004), and there was a trend for an association between TSAT at week 12 and baseline CRP which achieved statistical significance at 12 months (p=0.02).ConclusionIn this study of factors predicting response to oral iron supplementation in IBD patients, the master iron regulator hepcidin did not seem to be a useful marker. However, there was a clear signal that CRP, as an indicator of chronic inflammation, did predict responsiveness of the body’s iron stores to replenishment with orally administered iron. The association between ferritin and CRP at week 12 and also between CRP and TSAT at 12 months but lack of association between CRP and haemoglobin suggests that, in the presence of elevated CRP, iron supplementation may need to be given for longer to replace iron stores. We suggest that the commonly available acute phase protein CRP should be measured in IBD patients with iron deficiency to help clinicians decide on the most appropriate route of iron supplementationReferences. Lugg S et al. JCC2014;8:876–880.. Dignass A et al. JCC2015;9:211–222.. Iqbal T et al. Dig Dis Sci2015;60:1375–1381.. Gasche C et al. IBD2015;21:579–588.Disclosure of InterestN. Quraishi: None Declared, S Smith: None Declared, D Ward: None Declared, N Sharma: None Declared, M Sampson Conflict with: Shield Therapeutics, C Tselepis: None Declared, T Iqbal Conflict with: speaker fee from Shield

IntroductionDisturbance in gut microbiota (dysbiosis) is a characteristic feature of ulcerative colitis (UC). It remains unclear whether this dysbiosis contributes to disease pathogenesis by driving immune dysregulation or is merely secondary to mucosal inflammation. We aimed to determine whether dysbiosis varied between areas of inflamed and non-inflamed colon in patients with UC and whether this was associated with a humoral immune response.MethodWe collected colonic biopsies from histologically confirmed areas of inflamed and non-inflamed colon from 15 patients with active UC. DNA was extracted and gut microbiota was characterised using 16s rRNA based analysis. Inferred metagenomic analysis for microbial function was performed by PICRUSt. As a marker of mucosal humoral immune responses, inflamed and non-inflamed colonic biopsy samples were cultured for 1 to 3 days prior to measurement of total immunoglobulin (Ig) production by ELISA.ResultsConsistent with previous observations patients with UC demonstrated reduced bacterial diversity with an increase in Proteobacteria, Bacteroides and Clostridiales species along with a decrease in Firmicutes to Bacteroides ratio. No differences were found in the microbial diversity nor phylae and genera in mucosally adherent gut microbiota between inflamed and non-inflamed colonic segments in patients with active UC. This observation was also seen when patients were subdivided based on disease activity as defined by Mayo scoring. PICRUSt analysis revealed genes associated with bacterial chemotaxis, motility and flagellar assembly were enriched in the inflamed tissue. Total Ig production did not differ between inflamed (n=6, mean 4966 +/- sd 3670 ng/ml) and non-inflamed tissue (n=11; mean 5756 +/- sd 8989 ng/ml; p>0.05) suggesting that equal numbers of antibody-producing B cells are present.ConclusionWe have demonstrated that the dysbiosis observed in patients with UC is consistent and is not influenced by mucosal inflammation or disease activity. Genes associated with bacterial invasion and flagellin are enriched at sites of inflammation. Mucosal Ig production was not upregulated at sites of inflammation possibly suggestive of a uniform humoral response. These functional pathways in colitis associated inflammation provide insight into contribution of microbiota in its pathogenesis.Disclosure of InterestNone Declared

IntroductionHelicobacter pyloriis a Gram-negative bacterium, which infects over 50% of the population worldwide. However, only a subset of these infections result in gastrointestinal diseases, such as peptic ulceration (10%) and gastric cancer (2%). Several epidemiological studies have revealed that people who carry H. pyloriare at a decreased risk of developing IBD. However, a mechanistic understanding of the association between H. pyloriinfection and IBD is still unknown. Unlike any other microbial species, once H. pyloricolonises its gastric niche, it is able to dominate the gastric microbiome, representing 90%–95% of the total microbial population. Therefore, we hypothesised that the presence of H. pyloriin the upper gastrointestinal (GI) tract prevents the colonisation of the lower GI tract with microbial species associated with the pathogenesis of IBD.MethodTo test this, we collected stool samples from IBD patients (comprising Ulcerative Colitis and Crohn’s disease patients) and determined their H. pyloristatus using a stool antigen test. We then characterised the intestinal microbiota of H. pyloripositive (n=9) and negative IBD patients (n=18), by amplifying the V4 hyper-variable region of the 16S rRNA gene from faecal DNA. To determine the predominant phyla, these products were sequenced using the Illumina MiSeq and data analysis was performed using the QIIME pipeline and GreenGenes database.ResultsInterestingly, bacterial community structure revealed that there is a strong trend towards a decrease of Proteobacteria and an increase of Bacteroidetes in H. pyloripositive IBD patients. Of note, IBD is generally characterised by an increase in Proteobacteria and a decrease in Bacteroidetes. Furthermore, using PICRUSt to investigate the functional composition of the metagenomes, we found that the H. pyloripositive IBD patients displayed significant functional differences, including decreased bacterial motility and chemotaxis (p=<0.05), demonstrating suppression of virulence traits.ConclusionOur preliminary data suggests that the presence of H. pyloriinfection may promote a less pathogenic intestinal microbiome in patients with established IBD. This data provides the rationale to extend our studies with increased patient numbers and healthy controls to determine the mechanistic basis for the negative association of H. pyloriinfection and IBD.Disclosure of InterestNone Declared

In a novel application SERRS has been used, by employing a silver sol, to monitor and analyse the conversion of indigo into the indigo carmine dye.

In a novel application SERRS has been used, by employing a silver sol, to monitor and analyse the conversion of indigo into the indigo carmine dye.

This article has no abstract. To view the article, select the ''View Print Version (PDF)'' link above.

A significant reduction in the optical losses of AIF3-based, infrared transmitting fibres has been achieved for the first time. A minimum loss of 0.05dB/m at 2.65μm coupled with extended transparency beyond 4μm and excellent chemical durability makes these fibres excellent candidates for infrared sensing, remote spectroscopy, laser power delivery and active fibre research.

The nonatrienes (VII) are prepared from the aldehyde (I) as shown in the reaction scheme.