Intestinal tuberculosis: a diagnostic challenge.

OBJECTIVE: To describe characteristics, presentation, time to diagnosis and diagnostic findings of patients with intestinal tuberculosis (ITB) in a low-burden country. METHOD: Retrospective study of 61 consecutive ITB patients diagnosed between 2008 and 2014 at a large East London hospital. RESULTS: Forty of sixty-one patients were male. Mean age was 34.6 years. 93% of patients were born abroad, mostly from TB-endemic areas (Indian subcontinent: 88%, Africa: 9%). 25% had concomitant pulmonary TB. Median time from symptom onset to ITB diagnosis was 13 weeks (IQR 3-26 weeks). Ten patients were initially treated for IBD, although patients had ITB. The main sites of ITB involvement were the ileocaecum (44%) or small bowel (34%). Five patients had isolated perianal disease. Colonoscopy confirmed a diagnosis of ITB in 77% of those performed. 42 of 61 patients had a diagnosis of ITB confirmed on positive histology and/or microbiology. CONCLUSION: Diagnosis of ITB is often delayed, which may result in significant morbidity. ITB should be excluded in patients with abdominal complaints who come from TB-endemic areas to establish prompt diagnosis and treatment. Diagnosis is challenging but aided by axial imaging, colonoscopy and tissue biopsy for TB culture and histology.

Factors associated with thiopurine non-adherence in patients with inflammatory bowel disease.

BACKGROUND: Medication non-adherence seems to be a particular problem in younger patients with inflammatory bowel disease (IBD) and has a negative impact on disease outcome. AIMS: To assess whether non-adherence, defined using thiopurine metabolite levels, is more common in young adults attending a transition clinic than adults with IBD and whether psychological co-morbidity is a contributing factor. We also determined the usefulness of the Modified Morisky 8-item Adherence Scale (MMAS-8) to detect non-adherence. METHODS: Seventy young adults [51% (36) male] and 74 [62% (46) male] adults were included. Psychological co-morbidity was assessed using the Hospital Anxiety Depression Scale (HADS) and self-reported adherence using the MMAS-8. RESULTS: Twelve percent (18/144) of the patients were non-adherent. Multivariate analysis [OR, (95% CI), P value] confirmed that being young adult [6.1 (1.7-22.5), 0.001], of lower socio-economic status [1.1 (1.0-1.1), <0.01] and reporting higher HADS-D scores [1.2 (1.0-1.4), 0.01] were associated with non-adherence. Receiver operator curve analysis of MMAS-8 scores gave an area under the curve (95% CI) of 0.85 (0.77-0.92), (P < 0.0001): using a cut-off of <6, the MMAS-8 score has a sensitivity of 94% and a specificity of 64% to predict thiopurine non-adherence. Non-adherence was associated with escalation in therapy, hospital admission and surgeries in the subsequent 6 months of follow up. CONCLUSIONS: Non-adherence to thiopurines is more common in young adults with inflammatory bowel disease, and is associated with lower socio-economic status and depression. The high negative predictive value of MMAS-8 scores <6 suggests that it could be a useful screen for thiopurine non-adherence.

Do antidepressants influence the disease course in inflammatory bowel disease? A retrospective case-matched observational study.

BACKGROUND: Depression, like adverse events and psychological stress, can trigger relapse in inflammatory bowel disease (IBD); however, the effects of psychoactive drugs on disease course are unclear. METHODS: Using retrospective electronic case note review, after exclusion of five patients on low-dose tricyclic antidepressants we compared the course of IBD in 29 patients (14 ulcerative colitis and 15 Crohn's disease), during the years before (year 1) and after (year 2) they were started on an antidepressant for a concomitant mood disorder to that of controls matched for age, sex, disease type, medication at baseline, and relapse rate in year 1. RESULTS: Patients had fewer relapses and courses of steroids in the year after starting an antidepressant than in the year before (1 [0-4] (median [range]) vs. 0 [0-4], P = 0.002; 1 [0-3] vs. 0 [0-4], P < 0.001, respectively); the controls showed no changes between years 1 and 2 in relapses (1 [0-4] vs. 1 [0-3], respectively) or courses of steroids (1 [0-2] vs. 0 [0-3]). Although there were no differences in the use of other relapse-related medications, outpatient attendances, or hospital admissions, the number of endoscopies fell significantly in the antidepressant group in year 2 compared with year 1 (P < 0.01). No such changes were seen in the controls. CONCLUSIONS: Antidepressants, when used to treat concomitant mood disorders in IBD, seem to reduce relapse rates, use of steroids, and endoscopies in the year after their introduction. These results suggest the need for a prospective controlled trial to evaluate their effects on disease course in patients with IBD.

Poster presentations at medical conferences: an effective way of disseminating research?

This study aimed to ascertain the value of posters at medical meetings to presenters and delegates. The usefulness of posters to presenters at national and international meetings was evaluated by assessing the numbers of delegates visiting them and the reasons why they visited. Memorability of selected posters was assessed and factors influencing their appeal to expert delegates identified. At both the national and international meetings, very few delegates (< 5%) visited posters. Only a minority read them and fewer asked useful questions. Recall of content was so poor that it prevented identification of factors improving their memorability. Factors increasing posters' visual appeal included their scientific content, pictures/graphs and limited use of words. Few delegates visit posters and those doing so recall little of their content. To engage their audience, researchers should design visually appealing posters by presenting high quality data in pictures or graphs without an excess of words.

Mass casualty incidents: are NHS staff prepared? An audit of one NHS foundation trust.

BACKGROUND: Lack of knowledge of an NHS trust's major incident policies by clinical staff may result in poorly coordinated responses during a mass casualty incident (MCI). AIM: To audit knowledge of the major incident policy by clinical staff working in a central London major acute NHS trust designated to receive casualties on a 24-h basis during a MCI. METHODS: A 12-question proforma was distributed to 307 nursing and medical staff in the hospital, designed to assess their knowledge of the major incident policy. Completed proformas were collected over a 2-month period between December 2006 and February 2007. RESULTS: A reply rate of 34% was obtained, with a reasonable representation from all disciplines ranging from nurses to consultants. Despite only 41% having read the policy in full, 70% knew the correct immediate action to take if informed of major incident activation. 76% knew the correct stand-down procedure. 56% knew the correct reporting point but less than 25% knew that an action card system was utilised. Nurses had significantly (p<0.01) more awareness of the policy than doctors. CONCLUSION: In view of the heightened terrorist threat in London, knowledge of major incident policy is essential. The high percentage of positive responses relating to immediate and stand-down actions reflects the rolling trust-wide MCI education programme and the organisational memory of the trust following several previous MCI in the capital. There is still scope for an improvement in awareness, however, particularly concerning knowledge of action cards, which are now displayed routinely throughout clinical areas and will be incorporated into induction packs.

Review article: complementary and alternative therapies for inflammatory bowel disease.

Complementary and alternative medicine includes a wide range of practices and therapies outside the realms of conventional western medicine. Despite a lack of scientific data in the form of controlled trials for either efficacy or safety of complementary and alternative medicine, use by patients with inflammatory bowel disease, particularly of herbal therapies, is widespread and increasing. There is limited controlled evidence indicating efficacy of traditional Chinese medicines, aloe vera gel, wheat grass juice, Boswellia serrata and bovine colostrum enemas in ulcerative colitis. Encouraging results have also been reported in small studies of acupuncture for Crohn's disease and ulcerative colitis. Contrary to popular belief, natural therapies are not necessarily safe: fatal hepatic and irreversible renal failure have occurred with some preparations and interactions with conventional drugs are potentially dangerous. There is a need for further controlled clinical trials of the potential efficacy of complementary and alternative approaches in inflammatory bowel disease, together with enhanced legislation to maximize their quality and safety.

Randomized, double-blind, placebo-controlled trial of oral aloe vera gel for active ulcerative colitis.

BACKGROUND: The herbal preparation, aloe vera, has been claimed to have anti-inflammatory effects and, despite a lack of evidence of its therapeutic efficacy, is widely used by patients with inflammatory bowel disease. AIM: To perform a double-blind, randomized, placebo-controlled trial of the efficacy and safety of aloe vera gel for the treatment of mildly to moderately active ulcerative colitis. METHODS: Forty-four evaluable hospital out-patients were randomly given oral aloe vera gel or placebo, 100 mL twice daily for 4 weeks, in a 2 : 1 ratio. The primary outcome measures were clinical remission (Simple Clinical Colitis Activity Index /= 3 points; response was defined as remission or improvement), Baron score, histology score, haemoglobin, platelet count, erythrocyte sedimentation rate, C-reactive protein and albumin. RESULTS: Clinical remission, improvement and response occurred in nine (30%), 11 (37%) and 14 (47%), respectively, of 30 patients given aloe vera, compared with one (7%) [P = 0.09; odds ratio, 5.6 (0.6-49)], one (7%) [P = 0.06; odds ratio, 7.5 (0.9-66)] and two (14%) [P < 0.05; odds ratio, 5.3 (1.0-27)], respectively, of 14 patients taking placebo. The Simple Clinical Colitis Activity Index and histological scores decreased significantly during treatment with aloe vera (P = 0.01 and P = 0.03, respectively), but not with placebo. Sigmoidoscopic scores and laboratory variables showed no significant differences between aloe vera and placebo. Adverse events were minor and similar in both groups of patients. CONCLUSION: Oral aloe vera taken for 4 weeks produced a clinical response more often than placebo; it also reduced the histological disease activity and appeared to be safe. Further evaluation of the therapeutic potential of aloe vera gel in inflammatory bowel disease is needed.

Anti-inflammatory effects of aloe vera gel in human colorectal mucosa in vitro.

BACKGROUND: Oral aloe vera gel is widely used by patients with inflammatory bowel disease and is under therapeutic evaluation for this condition. AIM: To assess the effects of aloe vera in vitro on the production of reactive oxygen metabolites, eicosanoids and interleukin-8, all of which may be pathogenic in inflammatory bowel disease. METHODS: The anti-oxidant activity of aloe vera was assessed in two cell-free, radical-generating systems and by the chemiluminescence of incubated colorectal mucosal biopsies. Eicosanoid production by biopsies and interleukin-8 release by CaCo2 epithelial cells in the presence of aloe vera were measured by enzyme-linked immunosorbent assay. RESULTS: Aloe vera gel had a dose-dependent inhibitory effect on reactive oxygen metabolite production; 50% inhibition occurred at 1 in 1000 dilution in the phycoerythrin assay and at 1 in 10-50 dilution with biopsies. Aloe vera inhibited the production of prostaglandin E2 by 30% at 1 in 50 dilution (P = 0.03), but had no effect on thromboxane B2 production. The release of interleukin-8 by CaCo2 cells fell by 20% (P < 0.05) with aloe vera diluted at 1 in 100, but not at 1 in 10 or 1 in 1000 dilutions. CONCLUSION: The anti-inflammatory actions of aloe vera gel in vitro provide support for the proposal that it may have a therapeutic effect in inflammatory bowel disease.

Antioxidant effects of herbal therapies used by patients with inflammatory bowel disease: an in vitro study.

BACKGROUND: Herbal remedies used by patients for treatment of inflammatory bowel disease include slippery elm, fenugreek, devil's claw, Mexican yam, tormentil and wei tong ning, a traditional Chinese medicine. Reactive oxygen metabolites produced by inflamed colonic mucosa may be pathogenic. Aminosalicylates (5-ASA) are antioxidant and other such agents could be therapeutic. AIMS: To assess the antioxidant effects of herbal remedies in cell-free oxidant-generating systems and inflamed human colorectal biopsies. METHODS: Luminol-enhanced chemiluminescence in a xanthine/xanthine oxidase cell-free system was used to detect superoxide scavenging by herbs and 5-ASA, and fluorimetry to define peroxyl radical scavenging using a phycoerythrin degradation assay. Chemiluminescence was used to detect herbal effects on generation of oxygen radicals by mucosal biopsies from patients with active ulcerative colitis. RESULTS: Like 5-ASA, all herbs, except fenugreek, scavenged superoxide dose-dependently. All materials tested scavenged peroxyl dose-dependently. Oxygen radical release from biopsies was reduced after incubation in all herbs except Mexican yam, and by 5-ASA. CONCLUSIONS: All six herbal remedies have antioxidant effects. Fenugreek is not a superoxide scavenger, while Mexican yam did not inhibit radical generation by inflamed biopsies. Slippery elm, fenugreek, devil's claw, tormentil and wei tong ning merit formal evaluation as novel therapies in inflammatory bowel disease.

Plain abdominal radiographic features are not reliable markers of disease extent in active ulcerative colitis.

OBJECTIVES: The aims of this study were to assess the reliability of the distribution of fecal residue, mucosal irregularity, and colonic wall thickening on plain abdominal x-ray as markers of disease extent assessed by technetium-99 m hexamethylpropylene amine oxine-labeled leukocyte scans in active ulcerative colitis (UC). METHODS: Plain abdominal radiographs were blindly assessed for the distribution of fecal residue, mucosal irregularity, and colonic wall thickening (>3 mm) in 30 patients with active UC. Most patients were too sick to safely allow total colonoscopy. In 11 patients for whom details of disease extent were available from total colonoscopy or surgery undertaken at the time, there was a close correlation with disease extent defined by technetium-99 m hexamethylpropylene amine oxine-labeled leukocyte scans. Contemporaneous radiolabeled leukocyte scans were therefore used to assess disease extent in comparison with plain abdominal radiographs. RESULTS: Of 30 patients, 15 had pancolitis and 15 had subtotal or distal disease as indicated by radiolabeled leukocyte scans. The distribution of fecal residue on plain abdominal radiographs correctly identified disease extent defined on radiolabeled leukocyte scans in 40% of patients, overestimating it in 13% and underestimating it in 47%. There was no significant correlation between distribution of fecal residue on plain abdominal radiographs and disease extent on radiolabeled leukocyte scans or colonoscopy or surgery. Of patients with pancolitis, 60% had fecal residue present on plain abdominal radiograph with 40% showing stool distal to the hepatic flexure as well as in the right colon. For total UC on radiolabeled leukocyte scanning, the sensitivity and specificity of absence of fecal residue on plain abdominal radiographs were 40% and 80% respectively. Irregularity of mucosal edge and colonic wall thickening were even less accurate than fecal residue in defining disease extent. CONCLUSIONS: The distribution of fecal residue, irregularity of mucosal edge, and colonic wall thickening on plain abdominal radiography do not provide a reliable guide to disease extent in active UC.

Review article: herbal treatment in gastrointestinal and liver disease--benefits and dangers.

Herbal medicines are now used by up to 50% of the Western population, in a substantial minority of instances for the treatment or prevention of digestive disorders. Although most indications for the use of such remedies are anecdotally or traditionally derived, controlled trials suggest some benefits for ginger in nausea and vomiting, liquorice extracts in peptic ulceration, Chinese herbal medicine in irritable bowel syndrome, opium derivatives in diarrhoea and senna, ispaghula and sterculia in constipation. Herbal preparations contain many bioactive compounds with potentially deleterious as well as beneficial effects. There is clearly a need for greater education of patients and doctors about herbal therapy, for legislation to control the quality of herbal preparations, and in particular for further randomized controlled trials to establish the value and safety of such preparations in digestive and other disorders.

Fibrin Glue for Bleeding Peptic Ulcers.

Fibrin glue is a complex plasma-derived product formed by mixing human fibrinogen and human factor X111 with human thrombin and bovine aprotinin following virus inactivation. It has been used to treat bleeding peptic ulcer by injecting the material through a dual lumen endoscopy injection needle into the floor of the ulcer around the bleeding point. In experimental and uncontrolled studies in patients it appears effective and produces little tissue damage. A large randomized trial in 854 patients admitted because of bleeding peptic ulcer with active bleeding or non bleeding visible vessel at endoscopy suggests that repeated injection of fibrin tissue glue had a significantly lower rebleeding rate than single injection of the sclerosant polidocanol.

A comparison of the structure and properties of normal human transferrin and a genetic variant of human transferrin.

1. A rare genetic variant of human serum transferrin (TfBSHAW) is reported. 2. The variant and normal transferrins have been purified. 3. The two proteins have been shown to be identical with respect to their molecular weights, heat stability, iron uptake and absorbance spectra. 4. The amino acid substitution is thought to be isoleucine replaced by asparagine at either position 378 or position 381. 5. The ferric iron bound to the C-site of TfBSHAW is unstable in the presence of protons or 6 M urea.