Background The relationship between intestinal epithelial integrity and the development of intestinal disease is of increasing interest. A reduction in mucosal integrity has been associated with ulcerative colitis, Crohn’s disease and potentially could have links with colorectal cancer development. The Ussing chamber system can be utilised as a valuable tool for measuring gut integrity. Here we describe step-by-step methodology required to measure intestinal permeability of both mouse and human colonic tissue samples ex vivo, using the latest equipment and software. This system can be modified to accommodate other tissues. Methods An Ussing chamber was constructed and adapted to support both mouse and human tissue to measure intestinal permeability, using paracellular flux and electrical measurements. Two mouse models of intestinal inflammation (dextran sodium sulphate treatment and T regulatory cell depletion using C57BL/6-FoxP3 DTR mice) were used to validate the system along with human colonic biopsy samples. Results Distinct regional differences in permeability were consistently identified within mouse and healthy human colon. In particular, mice showed increased permeability in the mid colonic region. In humans the left colon is more permeable than the right. Furthermore, inflammatory conditions induced chemically or due to autoimmunity reduced intestinal integrity, validating the use of the system. Conclusions The Ussing chamber has been used for many years to measure barrier function. However, a clear and informative methods paper describing the setup of modern equipment and step-by-step procedure to measure mouse and human intestinal permeability isn’t available. The Ussing chamber system methodology we describe provides such detail to guide investigation of gut integrity. Electronic supplementary material The online version of this article (10.1186/s12876-019-1002-4) contains supplementary material, which is available to authorized users.
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The four identified subscales are clinically relevant and correspond to domains of patient satisfaction identified in previous studies. Our development and validation of the GESQ confirmed that it is a valid, reliable, interpretable, and acceptable tool to measure satisfaction in patients who have undergone a GI endoscopy.
SUMMARYAlthough colectomy for ulcerative colitis is curative, long-term quality of life is reduced.Intravenous ciclosporin 4 mg/kg/day has significant toxicity. There is now evidence that low-dose ciclosporin (2 mg/kg daily by intravenous infusion, or 5-6 mg/kg daily in a twice daily oral dosage) has an acceptable safety profile, even when used in combination with corticosteroids. Drug dosage should be adjusted to the levels of 150-250 ng/mL initially (random levels during intravenous infusion, or trough levels for oral use).Ciclosporin should be considered not only in those who have failed 7 days of corticosteroids, but also in fulminant colitis at day 3, if not responding to corticosteroids. The drug should be avoided in frail or elderly patients with significant comorbidity, and also where colectomy is likely to be necessary in the short to medium term. Ciclosporin should not be continued for more than 7 days, unless there is a definite response. A 70-80% initial response is likely, and responders are discharged on oral ciclosporin, adding thiopurines and tailing prednisolone rapidly. The drug should be continued for 3 months. The likelihood of avoiding colectomy over 2-3 years is 40-50%. More studies are needed to evaluate the use of oral ciclosporin in corticosteroid-refractory colitis in outpatients, and to assess whether monotherapy (without corticosteroids) is significantly safer, without loss of efficacy. INTRODUCTIONSevere ulcerative colitis (UC) is a potentially lifethreatening condition. It is widely accepted that around 15% of patients with UC will be affected by a severe flare-up and will require in-patient treatment. Traditional treatment for such patients is with high-dose intravenous (i.v.) corticosteroids but up to 40% of patients become refractory to this treatment. Complications of severe UC include toxic dilatation of the colon, perforation and severe bleeding. Surgery cures UC but has potential surgical morbidity, and long-term quality of life issues related to ileoanal pouches or permanent ileostomy. The use of i.v. ciclosporin was first reported in UC in 1984.1 This potent drug has been slow to gain acceptance as a standard therapy because of concerns about toxicity. Although there is a risk of drug toxicity, most patients will opt for ciclosporin if offered, rather than undergoing colectomy. A study from Cohen et al.2 assessed 42 patients who received ciclosporin during an acute severe relapse. They found that patients who retained their colon felt physically and psychologically healthier with a significantly better quality of life compared with those who had undergone colectomy. In this paper, we present the evidence base for ciclosporin use and practical advice on how to maximize its effectiveness and safety. EVIDENCEWe undertook MEDLINE search using the following terminologies: Cyclosporine/Ciclosporin and UC/Inflammatory bowel disease; as key words (MeSH, Medical Subject Headings), a total of 294 articles were found.
Objective To compare the clinical effectiveness of doctors and nurses in undertaking upper and lower gastrointestinal endoscopy. Design Pragmatic trial with Zelen's randomisation before consent to minimise distortion of existing practice. Setting 23 hospitals in the United Kingdom. In six hospitals, nurses undertook both upper and lower gastrointestinal endoscopy, yielding a total of 29 centres. Participants 67 doctors and 30 nurses. Of 4964 potentially eligible patients, we randomised 4128 (83%) and recruited 1888 (38%) from July 2002 to June 2003. Interventions Diagnostic upper gastrointestinal endoscopy and flexible sigmoidoscopy, undertaken with or without sedation, with the standard preparation, techniques, and protocols of participating hospitals. After referral for either procedure, patients were randomised between doctors and nurses. Main outcome measures Gastrointestinal symptom rating questionnaire (primary outcome), gastrointestinal endoscopy satisfaction questionnaire and state-trait anxiety inventory (all analysed by intention to treat); immediate and delayed complications; quality of examination and corresponding report; patients' preferences for operator; and new diagnoses at one year (all analysed according to who carried out the procedure). Results There was no significant difference between groups in outcome at one day, one month, or one year after endoscopy, except that patients were more satisfied with nurses after one day. Nurses were also more thorough than doctors in examining the stomach and oesophagus. While quality of life scores were slightly better in patients the doctor group, this was not statistically significant. Conclusions Diagnostic endoscopy can be undertaken safely and effectively by nurses. Trial registration International standard RCT 8276570
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