Why Do I Keep Meeting The Wrong Men? (Brown Suga Collections Book 2)
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Carol Taylor, a former Random House book editor, has been in book publishing for over 18 years and has worked with many of today's top black writers. She lives in New York. Find her at insignificantothersbooks. Books by Carol Taylor. Trivia About Brown Sugar: No trivia or quizzes yet. Just a moment while we sign you in to your Goodreads account. Beattie 2 , G. Monteleone 4 , T. ResultsA significantly higher number of plasmacytoid DC were found in active coeliac disease than in controls.
ConclusionsIn active coeliac disease, lamina propria DC are activated and express higher number of transcripts of pathologically relevant cytokines. Preservation of this segment during right hemicolectomy will prevent loss of its function. The arterial supply was dissected to demonstrate a pattern. BackgroundWith the advent of capsule endoscopy CE the role of push enteroscopy PE needs to be reassessed. AimTo evaluate the diagnostic yield of PE in relation to referral indication.
We also compared the diagnostic yield in patients who had CE followed by PE against those who only had a PE performed. MethodsAll patients who underwent push enteroscopy from January to August were included in this retrospective audit. Of these there were 63 cases where both PE and CE were performed. PE was unsuccessful in seven patients due to anatomical strictures or patient distress. Overt bleeding was also compared to individual subgroups: There were no cases where PE recognised a lesion that had not already been detected at CE.
ConclusionPush enteroscopy has the greatest diagnostic yield in overt bleeders when compared to other referral indications. A negative CE would appear to exclude the need for a PE. PE should be used for therapeutic intervention following CE. Habitual intakes using weighed food diary were measured along with urinary and stool N losses over a five day period. BackgroundChronic sodium Na and water depletion is well recognised in colectomy patients with ileostomies.
The withdrawal of Na from intravenous nutrition has been shown to inhibit retention of nitrogen N and calcium Ca in underweight adults leading to the failure of lean tissue and bone mineral repletion. Results are presented in median range. ConclusionsIleostomy patients who have Na depletion are not only at risk of renal impairment from chronic dehydration but may also have compromised nitrogen and mineral status.
These patients, who are often asymptomatic, are therefore at risk of subclinical malnutrition and osteoporosis. Grencis 1 , J. BackgroundThe molecular mechanisms linking enteric inflammation to reduced food intake are poorly understood, despite their clinical significance. This model is now underpinning a mechanistic study of the mediators responsible for reduced food intake during gut inflammation.
Daily food intake and body weight were monitored. ResultsWT mice displayed a significant fall in food intake: Body weight during infection fell to Body weight again fell to At day 20, WT mice retained 1. BackgroundPeristomal wound infection is a common complication of percutaneous endoscopic gastrostomy PEG especially in hospitals where methicillin resistant Staphylococcus aureus MRSA is endemic. Recent evidence suggests antibiotic prophylaxis at the time of PEG insertion may reduce infection rates.
Peristomal wound sites were monitored for one month post PEG insertion for inflammation, purulent discharge and infected looking sites were swabbed. In MRSA endemic clinical areas the risk of developing wound site infection may remain for some time post procedure unless high standard wound care is maintained. No long term reports of central venous catheter CVC sepsis rates have been reported from a district general hospital in the UK.
We have already demonstrated that CVC sepsis rates in our home parenteral nutrition patients are comparable to those in large tertiary centres. MethodsCumulative prospectively collected annual data of CVC sepsis rates from to at a single district general hospital in all patients receiving parenteral nutrition via a central venous catheter. Sixty four CVC lines were infected. CVC sepsis varied from 0—16 per year with a mean of 3. Before the mean sepsis rate was ConclusionsCVC sepsis rates fell dramatically with the introduction of a nutrition team. They compare well with those obtained from tertiary centre nutrition teams and support the recommendations of NICE, The Royal College of Physicians, and King's Fund that every acute trust should have a nutrition team.
Steinhart 1 , A.
Liver free papers
Forbes 2 , A. Bhatt 3 , S. BackgroundResearch indicates that the maintenance of quiescent Crohn's disease with oral mesalazines is most frequently observed following surgical rather than medically induced remission. Studies assessing the effectiveness of mesalazine in treating patients with medically induced remission have yielded inconsistent results. It is possible that these inconsistencies arise from differences in the formulation of mesalazine administered. ResultsTreatment with pH7 dependent mesalazine significantly reduced the risk of symptomatic relapse pooled OR 0. Moreover, pH7 dependent mesalazine may offer an effective treatment for maintaining medically induced remission of Crohn's disease.
Di Sabatino 1 2 3 , M. Buckley 1 , K. Pickard 1 , R. Morera 3 , P. Cazzola 3 , G. Corazza 3 , T. MacDonald 1 2 , S. As expected, Smad7 was strongly upregulated in CD inflamed mucosa. IntroductionPsychological stress is reported to increase relapse in ulcerative colitis UC but the mechanism is unclear. Autonomic response was assessed by pulse and BP changes. ResultsThe control protocol did not change any variable. Both mechanisms could contribute to the pathogenic effects of psychological stress in UC. MethodsSurgical resection specimens of terminal ileum 6 normal, 7 Crohn's disease and colon 4 normal, 7 IBD were studied.
Tissue sections were used for immunohistochemistry. Paneth cell containing epithelial crypts were detached from mucosal strips with EDTA. Similar results were seen using elastase treated supernatants prepared from CD, colon cancer, and control E coli. Much of this stimulatory activity is present in shed microvesicles. This process, which is only partially related to bacterial adhesion, may be at least as relevant to UC as to Crohn's disease.
Hanauer 1 , M. Lukas 2 , D. Macintosh 3 , P. Pollack 4 , J. Kent 5 , introduced by S. AE were generally mild to moderate. In all, 54 SAE occurred in 37 patients. Improvements were long lasting. Adalimumab was well tolerated. BackgroundIncreasing evidence implicates the disruption of xenobiotic defence mechanisms in the pathogenesis of inflammatory bowel disease IBD.
Further fine mapping of associated interval of the implicated SNPs and replication in other datasets are in progress, together with functional and expression data. Mirza 1 , S. Fisher 1 , C. Onnie 1 , J. Sanderson 2 , A. Forbes 3 , J. Mansfield 4 , C. Lewis 1 , C. Our aim was to investigate conflicting evidence of a role for TUCAN in IBD susceptibility by sequencing the coding region of the gene in IBD patients and testing single nucleotide polymorphisms for association in a large case control sample. ResultsSequencing detected six SNPs: However, the frameshift insAA was not significantly different in cases of CD 5.
This result requires independent replication in other patient cohorts. AimUlcerative colitis UC is a chronic inflammatory condition that increases the risk of developing colorectal cancer CRC. LOH analysis can be used as a simple and reliable marker of clonality. The aim of this study was to use LOH at the above three loci for the assessment of clonality within dysplastic and inflamed tissue in UC to test the hypothesis that dysplastic lesions arise from a single mutated clone.
MethodsParaffin embedded tissue from colectomy specimens was obtained from St Marks Hospital pathology library. Laser capture microdissection was used to isolate individual crypts. If no normal crypts were available from the tissue, regions of lamina propria or muscularis mucosae were taken to allow LOH analysis comparison. PCR product was analysed with ABI sequencer and genotyper software and abnormal tissue allelic areas were compared with normal tissue allelic areas as a ratio.
LOH of multiple markers was seen in some patients. ConclusionsLower LOH frequency in inflamed and low grade dysplasia compared to high grade dysplasia suggests which marker is lost first, and the earliest lost marker can be used a clonal marker. Increased crypt fission is likely to be responsible for mutation spread. Nunes 1 , M.
Escudier 2 , P. Shirlaw 2 , S. Challacombe 2 , J. BackgroundOrofacial granulomatosis OFG is a rare chronic inflammatory disease of unknown aetiology sharing histological features with gut Crohn's disease CD. Previous studies addressing the clinical features and natural history of OFG are limited. AimsTo gain insight into the overall presentation and clinical features in patients with OFG referred to a dedicated OFG tertiary referral centre.
Data were extracted for age of onset, sex, clinical features, blood parameters, concurrent CD, and patch testing. A concurrent diagnosis of CD was established by standard criteria. ConclusionOFG affects predominantly young adults with lip and buccal involvement the most common clinical presentation.
Mucosal tags and cobblestoning are more likely in those with concurrent CD. MethodsHospital Episode Statistics data for the year —04 were obtained from The Department of Health and imported into a database Access for analysis. ConclusionTwenty five per cent of patients with AP will be predicted severe. We would recommend that further work is undertaken to develop the guidelines, looking at levels of monitoring required and where this is best initiated, minimal levels of supportive care, and routine use of scoring systems that would allow the prioritisation of patients with organ dysfunction to a higher level of care.
Forman 1 , B. AimTo investigate the impact of deprivation on outcome in patients with pancreatic cancer, data were collected from the NYCRIS Northern and Yorkshire Cancer Registry database for new patients registered from January to December MethodsThe IMD score a validated socioeconomic deprivation tool was attributed to each patient.
Five quintile groups of similar size were generated with graded deprivation profiles, higher scores representing greater deprivation. The difference between the rank of socioeconomic deprivation and average survival in days was also calculated for the cohort of patients who underwent surgery and those who had no surgical intervention. ConclusionAlthough the cohorts represent a varied casemix, socioeconomic deprivation appears to have a major effect on survival in patients with pancreatic cancer and also correlates with treatment by surgical intervention.
Further work is required to determine the underlying cause of this effect. Hunt 1 , S. Ghosh 1 , K. King 2 , S. Gabe 3 , C. Mathew 2 , A. Forbes 3 , R. Three common mutations ArgTrp, GlyArg, Leufs impair innate immune responses to bacterial muramyl dipeptide. Rare NOD2 variants occur, but it is difficult to both identify them and assess their functional effect.
We assessed the true frequency of defective muramyl dipeptide sensing in Crohn's disease and developed a rapid diagnostic assay. MethodsAn ex vivo assay was established and validated based on muramyl dipeptide stimulation of peripheral blood mononuclear cell cytokine production. Assay results were compared with NOD2 genotype status three common mutations and rare variants in 91 individuals including a prospective cohort of 49 Crohn's disease patients. Disease state, active inflammation or concurrent use of immunosuppressive medication did not influence results.
Inherited mutations in NOD2 and not any other genes accounted for all defects. The ex vivo assay has multiple potential applications as a clinical diagnostic tool to distinguish patients with muramyl dipeptide sensing defects, and for research investigation. Gordon 1 , K. Pickard 1 , P. Goggin 2 , T. IntroductionIn both ulcerative colitis and Crohn's disease there is a marked increase in IgG plasma cells in the lamina propria which may be of primary pathogenic significance.
In addition, gut plasma cells can secrete functionally active immune mediators capable of driving inflammation in the gut. Using a novel method for isolating gut plasma cells we have previously shown that long lived IgG plasma cells persist in inflammatory bowel disease IBD and may contribute to tissue injury. MethodsBiopsy and resection tissue specimens were obtained from patients with active IBD and from normal controls. Lamina propria mononuclear cells were isolated and immunomagnetic selection used to positively select plasma cell populations.
The types of plasma cell making MMP3 were studied by confocal microscopy. These results identify a new pathway by which IgG plasma cells can damage the gut. Part of this miss rate may be due to lesions hidden in colon that is inadequately distended to allow complete visualisation of the mucosal surface.
Changing the patient's position during colonoscopy may alter colonic configuration and gas distribution to improve luminal distension, compared to performing the entire withdrawal sequence in the left lateral position. MethodDuring the withdrawal phase, 14 patients were randomised to one of two sequences first: Position change involved examination of caecum C , ascending colon AC , and hepatic flexure HF in left lateral; transverse colon TC supine; and splenic flexure SF and descending colon DC in right lateral.
Luminal distension was scored on a scale 1—5: ConclusionPosition change during the withdrawal phase of colonoscopy improves luminal distension in the transverse colon, splenic flexure, and descending colon compared to examination in the left lateral position, and has the potential to reduce adenoma miss rates.
Rampton 1 , B. Retrospective case series Endoscopy ; Five of seven patients in the steroid group required redilatation and two of these five subsequently required surgery. One of six patients in the placebo group required redilatation, none required surgery. ConclusionIn this small trial, intrastricture steroid injection post balloon dilatation of Crohn's disease related ileocolonic anastomotic strictures does not extend time to redilatation and may shorten it.
Steroid injection after stricture dilatation should be reconsidered. Hurlstone 1 , D. Sanders 1 , M. McAlindon 1 , A. Lobo 1 , M. Thomson 1 , S. Brown 1 , S. Interval cancers are known to occur. AimsWe hypothesised that targeted chromoscopy alone with high magnification imaging may increase the total number of intraepithelial neoplastic lesions detected as compared to conventional colonoscopy and biopsy protocols.
Defined lesions were further evaluated using modified Kudo crypt pattern analysis and Paris guidelines. Data were compared to disease and extent matched controls who had undergone conventional colonoscopic surveillance between January —April However, from the targeted biopsy group without HMCC imaging, the yield was modestly improved at 1. ConclusionsMagnification chromoscopy significantly improves the detection of IN in this group. These techniques have important clinical implications and may change current practice guidelines.
BackgroundNarrow band imaging NBI uses optical filters to improve contrast for superficial mucosal vessels to highlight vascular neoplastic lesions as well as the mucosal pit pattern. Autofluorescence imaging AFI relies on neoplastic lesions blocking endogenous tissue autofluorescence to provide colour contrast magenta on green against the background mucosa. ResultsMean adenoma detection rate was 0. Chromoendoscopy seems to provide a slightly clearer pit pattern and contrast for very small lesions. NBI provides many of the advantages of chromoendoscopy without requirements of extra time and equipment, and problems with incomplete mucosal coverage.
AFI is not yet consistent enough to replace standard endoscopy but may be a valuable adjunct to NBI in endoscopic assessment of polyps for neoplasia in equivocal cases. Webster 1 , R. Doshi 2 , A. BackgroundEmbarrassment and ignorance about colonic disease is widespread, yet this needs to be overcome if the national colorectal cancer screening programme is to be a success.
On advancing proximally, a small sessile polyp is identified. Over further years it enlarges and undergoes malignant change the voice over stresses that only a small proportion of polyps become malignant. Information graphics are used to help convey some of the genetic changes that must occur for the polyp ultimately to become cancerous.
The animation then follows the spread of the tumour as it moves through the bowel wall, demonstrating the Duke's stages of tumour invasion, and including haematogenous tumour spread to the liver. We end by showing a snare polypectomy which completely removes the polyp during its premalignant stage. ConclusionWe hope that this novel way of describing the dynamic nature of disease pathophysiology may be of use to both patients and doctors, and be applicable to other areas of gastroenterology teaching and practice.
IntroductionThere is a high prevalence of intestinal metaplasia and inflammation of the gastric cardia in H pylori negative healthy subjects. This may represent relaxation of the distal abdominal portion of the lower oesophageal sphincter LOS and consequently, gastric juice damaging the most distal oesophageal squamous mucosa. The LOS is under most strain following a large meal. MethodFifteen healthy volunteers, all H pylori negative by breath test, fasted on three separate occasions. Distances quoted are means and measured from the nares. ResultsFollowing the meal the total length of the LOS reduced from 4.
The upper border position did not change. The respiratory inversion point RIP elevated from The lower border of the LOS elevated from The thoracic portion of the LOS reduced from 2. The abdominal portion of the LOS reduced from 2. The maximum end expiratory pressure reduced from ConclusionThis study demonstrates shortening of the LOS after a meal due to shortening of the abdominal sphincter.
There is also slight shortening of the thoracic sphincter. There is movement of the RIP proximally, probably due to a mild elevation of the diaphragm caused by gastric distension. DiscussionShortening of the abdominal segment of the LOS following a large meal is likely to predispose to gastric acid reaching and damaging the squamocolumnar junction.
This may explain the high prevalence of carditis and intestinal metaplasia at the squamocolumnar junction. There was no difference in mean acid exposure day 1—4 8. BackgroundPrevious work has demonstrated the presence of an unbuffered pocket of highly acidic juice at the gastric cardia after a meal in healthy volunteers.
AimsTo compare the postprandial acid pocket in healthy volunteers and patients with severe reflux and to define its position relative to the squamocolumnar junction and manometric landmarks. At endoscopy radiopaque clips were placed at the proximal gatric folds and at the diaphragmatic pinch and barium meal documented the anatomy. ConclusionOesophagitis is associated with an enlarged unbuffered postprandial acid pocket. This may be due to the hiatus hernia providing a reservoir of highly acidic gastric juice isolated from food in the main stomach which may reflux into the oesophagus.
Anggiansah 1 , R. Anggiansah 1 , L. Cherkas 2 , T. Spector 2 , N. Sonwalkar 1 , O. Rotimi 2 , S. IntroductionBarrett's oesophagus BO and oesophageal adenocarcinoma OA is increasing over time in the last 2—3 decades. Population prevalence is Incidence of BO increased from 0. Community incidence increased from Aims and MethodIn this longitudinal, dynamic cohort study study period 1 October to 31 December , the aim was to establish the changing trends in the incidence and prevalence of dysplasia in patients with BO attending the General Infirmary at Leeds for endoscopy over the last two decades.
Barrett's oesophagus was defined as specialised intestinal metaplasia SIM on histology and dysplasia diagnosis was based on Riddell's and Vienna criteria. Histology, endoscopy, and case notes were reviewed. Dysplasia on index endoscopy or within six months was defined as prevalent and any subsequent dysplasia as incident. For prevalent dysplasia the denominator was the number of endoscopies performed and for incidence calculations the denominator was the number of cases of BO and number of OGDs in a year.
Prevalent cases were excluded from subsequent incidence measurements and tertiary referrals were excluded. However the prevalent patients had a longer mean length of BO. The cumulative incidence CI was 0. The incidence density ID increased from 14 to per surveillance years. There was an increasing trend towards the total number of dysplasias diagnosed each year. However, there were less dysplasia episodes both, total, and prevalent as a proportion of SIM diagnosis. Prevalent dysplasia doubled while the cumulative incidence went down slightly. ConclusionPatients with BO are twice likely to present with dysplasia on first endoscopy.
Further progression of dysplasia on surveillance is slightly reduced. There is more resource utilisation because of the increasing number of dysplasia episodes. IntroductionThe aim of any Barrett's surveillance programme is to detect early oesophageal adenocarcinoma AC arising in dysplastic Barrett's oesophagus BO. The natural history of high grade dysplasia HGD is still debated and the general opinion about the benign course of low grade dysplasia LGD has been challenged by some recent studies.
Patients and MethodsA retrospective analysis of patient records who developed dysplasia at some point during their BO surveillance between the periods of to , identified from a pathology database. All histopathology slides were reviewed according to Vienna classification, by an independent consultant GI histopathologist.
ResultsWe identified 67 cases of dysplasia in BO 48 male. After review, 13 patients were downgraded from LGD to no dysplasia ND and were subsequently excluded from further analysis. All cause mortality was Recent reports have suggested regional variations in cancer incidence in the west. References in retrieved papers and relevant review articles were scrutinised to identify papers missed on the initial search. Studies with patients who had histological confirmation of BO on surveillance, documented follow up data, and cancer as the outcome measure were included.
Follow up data of 50 patients entering an APC trial in 1 followed up to August were obtained from endoscopy and pathology; all patients' GPs were contacted. There was a significant reduction in length of Barrett's mucosa mean reduction 3. A mean of 9. No patient developed dysplasia or cancer. Initial length of Barrett's mucosa and final dose of maintenance PPI correlate with successful outcome. Luminal components such as acid and bile salts are thought to contribute to the neoplastic progression. For example, pulsatile acid and bile exposure can alter proliferation and differentiation status in ex vivo and in vitro models and low pH can induce DNA damage in vitro.
Recently, increased oesophageal concentrations of nitric oxide NO have been demonstrated in patients with BO. NO and its derivates have been shown to induce DNA damage in colorectal carcinogenesis.
Brown Sugar: A Collection of Erotic Black Fiction by Carol Taylor
Intracellular ROS production following acid treatment was assessed by flow cytometry using a fluorescent indicator. Long term survival was assessed by clonogenic assay. Mitochondria were not depolarised following exposure to low pH, ruling out mitochondrial damage as a source of ROS. Long term clonogenic survival studies demonstrated that cells were able to continue to grow following this initial insult. If not repaired correctly these lesions could lead to gross genetic and chromosomal abnormalities that may aid in the progression of BO to adenocarcinoma.
BackgroundSurgical resection remains the gold standard treatment of early oesophageal cancer although with an increasingly elderly population many patients are unfit for this radical therapy and less invasive curative options are required. AimTo relate our experience of photodynamic therapy PDT in treating early oesophageal cancer.
Patients were deemed medically unfit for major resectional surgery and were selected for PDT. All patients had follow up endoscopy at 6—12 week intervals indefinitely. Routine biopsies of the treated area were obtained. Eight of 20 patients who had initial complete response remain disease free at follow up of These strictures have required a median of five dilatations 1— Singh 1 , M.
Power 2 , P. Tyrrell 2 , D. Thompson 1 , S. BackgroundUp to half of patients suffering a stroke will be dysphagic; a complication that carries a sevenfold increased risk of pneumonia and is an independent predictor of mortality. AimsTo assess the longer term dose response effects of electrical pharyngeal stimulation in dysphagic stroke.
MethodsPatients admitted with a clinical diagnosis of acute anterior circulation stroke were screened with a standardised videofluoroscopic swallowing assessment. Dysphagic patients were randomised by minimisation to one of four treatment groups or to a control group with age and stroke severity the controlled factors. The four treatment groups received 10 minutes of stimulation daily or three times a day and for three or five days. The control group received no intervention. Change in aspiration severity at the follow up videofluoroscopy at two weeks was then determined.
ResultsOf 61 patients who underwent the baseline videofluoroscopy, 22 were found to be dysphagic and completed the study. Six were allocated to the control group with four in each active arm.
Brown Sugar: A Collection of Erotic Black Fiction
ConclusionThese initial data suggest there is a long term clinical benefit from electrical pharyngeal stimulation. Further clinical trials are underway. BackgroundWe have recently demonstrated that chemical stimuli in the small intestine induce sensations comparable to mechanical distension and that chemical hypersensitivity against capsaicin might exist in the small intestine of dyspeptic subjects.
Other patient groups inflammatory bowel disease with dyspeptic symptoms but no gastric involvement, peptic ulcer, other diseases had an aggregate perception score comparable to controls, but significantly less than NUD patients.
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ConclusionPatients with NUD are hypersensitive against gastric capsaicin. Phillips 1 , S. Williams 1 , Q. BackgroundDifferences between visceral and somatic pain perception have been explored with brain imaging, however little attention has been given to differences in autonomic nervous system ANS responses such as skin conductance response SCR and heart rate variability band variance BV. AimTo determine differences in selective ANS responses for visceral and somatic pain matched for intensity and temporal characteristics. MethodsIn 19 healthy adults eight male SCR, BV and heart rate HR were measured at baseline and in response to oesophageal balloon distension and thermal cutaneous stimuli at pain intensity.
ResultsHR was increased from baseline mean BV withdrawal from baseline 6. SCR latency was shorter for visceral 4. ConclusionIn comparison to somatic pain, the larger HR response to visceral pain was mediated by greater sympathetic activation despite lesser central cardiac parasympathetic withdrawal. These differential ANS responses for visceral pain may reflect its greater unpleasantness compared with somatic pain of the same intensity. Selective ANS measures hold promise both for understanding mechanisms and as markers of differences in pain response.
IntroductionAcute physical stress causes a measurable acute alteration of gut autonomic function and visceral hypersensitivity in patients with irritable bowel syndrome IBS Murray et al. We present the first report of the effects of amitriptyline on the gut neural response to acute stress. Patients underwent stress assessment at baseline and after three months of treatment. Physiological parameters measured included: DiscussionAmitriptyline is effective in constipation predominant IBS patients.
This effect is primarily on stress induced visceral hypersensitivity, independent of autonomic tone. The gut response to acute stress is a viable target to study drug efficacy in IBS. Jones 1 , D. Sudworth 1 , J. BackgroundVisceral hypersensitivity is an important pathophysiologic factor in irritable bowel syndrome IBS. Preclinical data indicate that pregabalin reduces trinitrobenzene sulfonic acid TNBS induced hypersensitivity but not basal sensitivity to colonic distension.
AimTo assess the effect of pregabalin on the perception of rectal distension in hypersensitive IBS patients. MethodsTwenty six rectally hypersensitive Rome II IBS patients aged 18—46 years, 7 male were included in a randomised, double blind, placebo controlled, parallel group study in which they received either three weeks oral pregabalin titrated: Baseline sensory thresholds were comparable between treatment groups.
An emax model provided the best fit to the compliance data. Pregabalin significantly increased rectal compliance slope of the volume pressure curve was 1. ConclusionsPregabalin increases the pain threshold to distension in IBS patients with rectal hypersensitivity. This may result from an increase in rectal compliance. IntroductionArtificial neural networks ANN are computer programs used to identify complex relations within data sets undetectable with conventional linear statistical analysis. One such complex problem is the prediction of need for lower gastrointestinal endoscopy in individual patients consulting for gastrointestinal symptoms.
Routine predictions have low accuracy and result in large numbers of normal colonscopies with obvious implications, both logistic and economic. We aimed to develop a neural network algorithm which can predict the need for lower gastrointestinal endoscopy in patients attending the routine outpatient clinics. MethodsProspective clinical data of patients undergoing elective colonoscopy were collected. The specifically developed questionnaire included 40 variables based on clinical features. The primary output was a positive finding on the colonoscopy, including polyps, cancer, diverticular disease, or colitis.
ResultsThe outcome and pathology reports of all patients were obtained and assessed. The results obtained highlight their obvious usefulness, which could now be used in a prospective evaluation for application of the technique. Murray 1 , N. Fyfe 1 , G. BackgroundChronic inflammation is a risk factor for many cancers yet its relevance to sporadic colorectal cancer is often dismissed. Most cancers arise from adenomatous polyps, which are constantly exposed to physical, chemical, microbial, and hypoxic stress. We hypothesise that chronic inflammatory activity within benign precancerous polyp tissue is central to cellular transformation towards colorectal malignancy.
AimsTo assess the inflammatory cell infiltrate in adenomatous polyps of varying sizes and their adjacent normal mucosa. Inflammatory cell infiltrate was assessed using immunohistochemistry. B cells, T H cells, T C cells, mast cells, and NK cells were present in similar numbers in both normal and polyp tissue. ConclusionInflammatory cell infiltrates are a key feature of adenomatous polyps and manifest as acute inflammation in small polyps and acute on chronic in larger polyps.
These findings may be relevant to the pathogenesis of sporadic colorectal cancer and the aetiology of this inflammatory activity warrants further investigation. Immunoreactivity was detected by signal amplification following heat induced antigen retrieval. A CRC tissue microarray was used as a positive control. ResultsThe colorectal cancer cores exhibited positive staining in the cytoplasm of neoplastic epithelial cells.
Immunoreactivity was focal with stromal positivity mainly localised to the periphery of the polyp lesions. Localisation of this was mainly in stromal cells. The stromal microenvironment of colonic adenomas and its interface with neoplastic epithelium may be important in cellular transformation towards malignancy, and warrants further investigation.
Greaves 1 , D. Taylor 1 , D. Furthermore, mtDNA mutations have been shown to accumulate within colonic crypt stem cells to levels that result in respiratory chain deficiency. The presence of mtDNA mutations within colonic crypt stem cells suggests that these mutations are present before the development of colorectal cancer, thus it is not unreasonable to suggest that mtDNA mutations may prove to be a putative biomarker of risk of CRC. AimTo characterise mtDNA mutational load in colonic crypts of patients with macroscopically normal colorectal mucosa. MethodsFresh frozen colorectal tissue from 21 patients 8 males with macroscopically normal colorectal mucosa were analysed histologically and histochemically.
These are results from the initial pilot study. COX deficiency was identified in colonic crypts of patients with macroscopically normal colon; thus confirming the presence of mtDNA mutations. These findings lend further support to the hypothesis that mtDNA mutational rate increases with age. Given that CRC occurs more commonly as we age there could be an association. ConclusionsWe have shown that COX deficient colonic crypts have been identified in the macroscopically normal colon.
Further studies on the influence of dietary intake on mtDNA mutational load are ongoing. Gillen 1 , R. BackgroundAutofluorescence AF has been developed to enhance conventional white light WL endoscopy in the diagnosis of neoplastic lesions of the GI tract. Metaplastic polyps are common and do not need to be treated, whereas adenomatous polyps carry a neoplastic potential. It would therefore be helpful to be able to distinguish between adenomatous polyps and metaplastic polyps when performing colonoscopy.
AimTo evaluate AF for the endoscopic detection and differentiation of colorectal polyps. The intensity of autofluorescence AI is quantified automatically and readings, pictures, and biopsies were recorded of any visible pathology or areas of high AF. The biopsy results were analysed and an AI reading for each biopsy site obtained by subtracting the actual AI reading from the background reading for the rectum of each patient.
A total of 33 polyps were detected 19 adenomatous and 14 metaplastic polyps. It was found that adenomatous polyps had higher AI readings median 0. ConclusionThese early data suggest that autofluorescence colonoscopy has the potential to differentiate between metaplastic and adenomatous polyps and may have a role as a new diagnostic technique for the improved detection of colonic dysplasia and early malignancy.
Ayaru 1 , S. Pereira 1 , T. Meyer 2 , B. Davidson 3 , A. Burroughs 3 , R. Williams 1 , S. There were no detectable responses in the controls. BackgroundFollowing on from classical animal studies and work on adenocarcinoma cell lines, recent gene targeted and transgenic mice studies have provided profound insights into the molecular determinants of epithelial renewal in the intestine. Despite, and because of, this progress, there is an increasing call for a complementary in vitro model of the intact human colonic epithelium. MethodsColonic crypts were isolated from tissue biopsies obtained at sigmoidoscopy from healthy subjects ethical approval.
Expression constructs and siRNA oligonucleotide duplexes were introduced to cells by low voltage square wave electroporation. A range of markers for cell polarity for example, NKCC1 , cell proliferation for example, BrdU incorporation and Ki67 , and viability for example, propidium iodide were employed. Intracellular calcium signalling was monitored in Fura2 loaded crypts. Expression of basolateral membrane transporters for example, NKCC1 and membrane receptors for example, M 3 AChR continued throughout the culture period as did the topological gradient of expression along the crypt axis.
Accordingly, the colonic crypt calcium wave signature induced by acetylcholine maintained its site of initiation at the base and unidirectional propagation along the crypt axis. The proliferative zone was maintained at the crypt base Ki67 positive. Cells were shed at crypt mouth and were positive for propidium iodide, whereas cells located elsewhere in the crypt excluded propidium iodide. We have demonstrated that many of the cellular processes associated with rapid renewal of the colonic epithelium are recapitulated ex vivo. Johnston 1 , V. The endoscopy Global Rating Scale GRS is a web based instrument designed to help endoscopy units deliver a patient focused service and assess how well they are doing.
The GRS includes 12 items that reflect the experience of a patient having an endoscopy.
The items are ranked into four levels: Level D is very basic and A is excellent. All endoscopy units in England were invited to complete the GRS on two census dates: April and October The results are presented as the percentage of A and B scores for each of the items. All items showed an increase in the percentage of A and B scores between the two census dates.
These data show that the GRS is an effective service improvement tool. BackgroundMany observational studies have found regular aspirin use is associated with a reduced risk of colorectal CR cancer and two randomised trials have shown that aspirin reduces risk of recurrent CR adenomas, although results were not wholly consistent.
MethodsA double blind, placebo controlled randomised trial was carried out in 10 centres nine in the UK and one in Denmark. All participants were followed up at intervals of four months to assess compliance, with a second colonoscopy arranged for three years after the date of trial entry. The primary outcome measure was a histologically confirmed CR adenoma or cancer either at the end examination or during the course of the trial.
Results patients were recruited into the study, of which receiving aspirin and placebo underwent a second colonoscopy and were included in an intention to treat analysis. Full compliance with trial medication was reported by patients. In total, Lassman 1 , S. McKie 1 , L. Gregory 1 , G. Dockray 2 , S. Williams 3 , D. This leads to modification of eating behaviour via activation of brainstem and hypothalamic neural circuits.
- Faith Among Shadows.
- The Gray Brethren and Other Fragments in Prose and Verse.
- A Gentlemans Promise: (Hot Regency Read) (Scandalous Series Book 1)!
MethodsFive fasted healthy volunteers underwent blood oxygenation level dependent BOLD functional magnetic resonance brain imaging using a 1. Visual analogue scores of satiety sensations were also recorded. ResultsA rapid and early increase in hypothalamic 1. ConclusionThis is the first demonstration of brainstem and hypothalamic activation by ingested lipid in normal humans and the feasibility of this type of approach using fMRI is hereby established.
BackgroundIntestinal fluid secretion is driven by transcellular active transport of chloride. NKCC1 mediates basolateral uptake of chloride and is emerging as a master controller of intestinal fluid secretion. Although it has long been established that acetylcholine ACh stimulates transient intestinal fluid secretion, the regulation of NKCC1 activation and its role in governing the nature of this response has not been investigated in the intact human colonic epithelium.
AimTo characterise NKCC1 expression along the human colonic crypt axis and study its activation by propagating cholinergic calcium signals. Total NKCC1 expression was probed for using a panel of polyclonal antibodies. Labelling was visualised using a FITC conjugated secondary antibody in conjunction with confocal microscopy and semiquantitative image analysis. ResultsNKCC1 exhibited an expression gradient along the crypt axis; labelling was basolateral and predominated at the crypt base.
The secretagogue acetylcholine ACh initiated calcium signals at the human colonic crypt base, which propagated in a unidirectional fashion along the entire crypt axis. ConclusionsA striking spatial correlation exists between ACh induced colonic crypt calcium signals, and calcium dependent NKCC1 activation.
These observations suggest that propagating cholinergic calcium signals coordinate fluid secretion along the human colonic crypt axis and that NKCC1 endocytosis may be an important mechanism in downregulating the secretory response. Taha 1 , W. Angerson 2 , R. As the incidence of upper gastrointestinal bleeding UGIB related to these agents has been increasing, we aimed at testing the Blatchford scoring system in predicting the clinical outcome in bleeders using these drugs. MethodsThe Blatchford scores cover risk factors and associated components measured on admission Lancet ; These include blood urea, haemoglobin, systolic blood pressure, pulse, melaena, syncope, hepatic disease, and cardiac failure.
ResultsThe median scores were as follows: They also correlate positively with the duration of admission, and can predict the need for transfusion in such patients. Ford 1 , A. Bailey 1 , D. Forman 2 , A. Axon 1 , P.
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IntroductionPopulation screening and treatment of Helicobacter pylori has been advocated to reduce mortality from gastric cancer. Screening programmes have been conducted in the West, but follow up was at two years, therefore long term mortality data are not yet available. Those testing positive were randomised to receive either eradication therapy, or placebo.
All those involved were traced with a list cleaning service provided by the Office for National Statistics, and death certificates were obtained for deceased individuals. ResultsOf original participants, 1. Mortality from all causes and IHD were significantly increased in H pylori positives compared to negatives odds ratios OR 1. ConclusionsInfection with H pylori is associated with an increased mortality from all causes, even when possible confounding factors are controlled for. However, screening and treatment of positive individuals may confer an increased risk of death from IHD, which should be borne in mind when recommending the adoption of such a strategy.
Hold 1 , M. Smith 1 , S. Berry 1 , K. McColl 2 , E. BackgroundThe innate immune system plays a crucial role in the initial handling of H pylori infection. Most of these genes have functionally relevant polymorphisms but apart from TLR4 , there have been few data on the role of these polymorphisms in H pylori pathogenesis. ResultsThere was a significant association between carriage of TLR9: These findings call for further evaluation of innate immune gene polymorphisms in the context of H pylori induced gastric cancer. Przemeck 1 , A. Varro 2 , D. IntroductionThe gastric antral hormone gastrin acts as a cofactor during gastric carcinogenesis and has been shown to regulate important cellular processes in the stomach including proliferation, migration, and differentiation.
In addition, several previous studies have shown that gastrin inhibits apoptosis. Various inhibitors were used to investigate relevant downstream signalling pathways. This demonstrates a novel pathway by which gastrin suppresses gastric epithelial apoptosis. Holzer 1 , A. In this study we wished to determine if capsaicin infusion into the proximal duodenum would result in increased excitability of spinal dorsal horn neurones and the development of sensitisation of convergent visceral and somatic structures.
MethodsWe recruited 16 subjects 12 female. A catheter was positioned in the proximal duodenum with a second in the distal oesophagus. Pain thresholds PT to electrical stimulation ES were assessed in the oesophagus, area of somatic referral AOR on the abdominal wall and control region Foot. Visual analogue scales VAS for pain, unpleasantness, nausea, and anxiety were recorded at five minute intervals during the infusion and a short McGill pain questionnaire was used.
No differences were seen in foot PT. The most common verbal descriptors used to describe the capsaicin infusion were cramping, hot burning, and aching. ConclusionCapsaicin infusion into the proximal duodenum induces sensitisation in visceral and somatic regions known to have convergent afferent input at the spinal cord level. The magnitude of sensitisation increases with increasing concentrations of capsaicin as does the subjective awareness of the infusion.
These data provide further evidence that central sensitisation plays an important role in the development of visceral hypersensitivity. Sandborn 1 , M. Lukas 2 , P. Rutgeerts 3 , P. ResultsOf 55 eligible patients randomised, 44 completed one year 33 randomised and 11 OL. Overall, AEs were mild to moderate in severity. ConclusionsIn this exploratory cohort, remission was maintained in patients treated for up to one year with adalimumab.
A definitive study powered to assess long term adalimumab efficacy is ongoing. Materials and MethodsPreliminary experiments showed that 0. This confirms the epithelial cell as the target for mesalazine JEM DNA damage induction is a key initiating mechanism in cancer development in most tissue types. Recent reports have shown that Barrett's tissues carry higher levels of DNA damage than squamous tissue, suggesting that Barrett's tissues are exposed to DNA damaging agents. Bile acids are implicated in oesophageal adenocarcinoma induction, although there is some contention as to whether they can cause DNA damage and it not known how they do so.
Hence, we assessed whether a range of bile acids were capable of inducing DNA damage in cultured oesophageal cells. Using the cytokinesis blocked micronucleus assay, we showed that DCA was the only bile acid tested that damaged chromosomes. We further showed that this damage was induced at both neutral and acidic pH pH6. DCA was also shown to induce point mutations in the human p53 gene, using the restriction site mutation assay.
Hence antioxidant supplementation may be an effective chemopreventative strategy in Barrett's patients. These observations are supported by epidemiological data showing that there is an inverse correlation between fruit and vegetable intake and cancer progression in Barrett's patients. Greaves 1 , S. Turnbull 1 , J. Studies on the intestine of animals and man have confirmed, beyond reasonable doubt, that the structural units, the crypts, are clonally derived.
The unit found in the stomach, the gastric gland, especially in the human, remains an enigma. Some animal reports show clonal derivation, whereas others show that a minority of glands remain polyclonal, suggesting the possibility of multiple, possibly independent stem cells. In the human, results are also mixed. We have used mutations in the mitochondrial cytochrome c oxidase subunit 1 gene COXsu1 , as a clonal marker J Clin Invest These suggest that a stem cell bearing this mutation expands to fill the entire gastric gland.
Moreover, the mutated gland then appears to spread in the mucosa by gland fission. Gastric glands undergo a process of monoclonal conversion, where the gland becomes gradually replaced by mutated cells. These mutated glands then appear to expand by gland fission, even in the adult stomach.
Ajamieh 1 , J. Berlanga 1 , O. Alba 1 , M. Marchbank 2 , J. Boyle 2 , F. Freyre 1 , D. Garcia del Barco 1 , P. Guillen 1 , S. Ghosh 2 , R. Goodlad 3 , R. Lung and renal injuries were also reduced by these pretreatments. Further studies appear justified.
BackgroundPatients with liver dysfunction are prone to infection which is frequently a precipitant of decompensation associated with hepatic encephalopathy, renal failure, and shock.