Specially processed cereals: a clinical innovation for children suffering from inflammatory bowel disease?
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Adolescent↗
Biomedical subjects
I Bjarnason
Publications and source records attributed to I Bjarnason.
Upper gastrointestinal endoscopy performed by nurses: scope for the future?
BACKGROUND: Previous researchers have shown that non-medical endoscopists can perform lower gastrointestinal endoscopy as safely and effectively as medical staff. However, it is not known if upper gastrointestinal endoscopy performed by medical and non-medical endoscopists in clinical practice yields similar results in terms of performance, patient discomfort, and satisfaction. AIM: To determine differences in the yield of diagnosis for significant disease during upper gastrointestinal endoscopy performed by nurse and medical endoscopists and to measure patient discomfort, satisfaction, and attitudes towards future endoscopy. PATIENTS: This two part study included 3009 patients in a retrospective analysis and 480 in a prospective study. METHODS: The first part of the study assessed indications for endoscopy, diagnoses, and procedures performed by medical and nurse endoscopists. In a second prospective study, 480 patients were included to determine the association between endoscopist type and sedation, patient anxiety, discomfort, satisfaction, and attitudes towards future sedation. RESULTS: No patient refused endoscopy by either a nurse or medical endoscopist and there were no complications in either group. Nurses performed 1487 procedures and reported fewer endoscopies as "normal" than medical staff (p=0.006). Multivariate analysis showed that male sex, older age, inpatient status, dysphagia, and gastrointestinal bleeding, but not endoscopist type, were all associated with significant disease. In relation to discomfort and satisfaction, a similar proportion of patients received sedation in both groups (p=0.81). There were no differences in pre-procedure anxiety (p=0.61), discomfort during intubation (p=0.97), discomfort during examination (p=0.90), or post-procedure examination rating (p=0.79) in patients examined by medical or nurse endoscopists. CONCLUSION: Experienced nurses perform routine diagnostic gastroscopy safely in everyday clinical practice and with as little discomfort and as much patient satisfaction as medical staff.
Age Factors↗
NSAIDs: the emperor's new dogma?
The spectacular marketing success of the selective cyclooxygenase 2 (COX-2) inhibitors is largely based on efficacy comparable with conventional non-steroidal anti-inflammatory drugs (NSAIDs) with vastly improved gastrointestinal safety. The additional key to the marketing success is the purity and simplicity of the message-that is, COX-1 inhibition causes the gastrointestinal side effects of NSAIDs (COX-1 dogma) while COX-2 blocking confers the therapeutic benefits (COX-2 dogma). Adherence to the COX dogmas with development of COX-2 selective agents has undoubtedly benefited many patients, but ironically their scientific basis is now seriously challenged by experimentation.
Animals↗
[Clinical and prognostic value of lesions in the gastrointestinal tract in systemic vascular purpura].
AIM: To evaluate clinical peculiarities and prognostic value of abdominal syndrome in adult patients with systemic vascular purpura (SVP). MATERIAL AND METHODS: Incidence, clinical picture, complications of abdominal syndrome, its relations with principal extraintestinal manifestations of SVP were studied in 125 SVP patients. Absorption and barrier functions of the small intestine, their correlations with clinical activity of the disease were investigated in 32 SVP patients with no clinical signs of intestinal affection. Computer-assisted morphometry of duodenal mucosa biopsies was conducted and the results were compared to those of intestinal permiability and clinical activity of SVP. RESULTS: Negative correlation was found between the occurrence of abdominal syndrome and the patients' age. The gastrointestinal tract suffered more frequently in men. 21% patients had abdominal complications, association of abdominal syndrome with higher frequency of glomerulonephritis. In the absence of abdominal symptoms, the barrier function of the small intestine for protein macromolecules was impaired. This correlated with exacerbations of skin purpura. Increased intestinal permeability and activity of skin purpura correlated with severity of inflammation in the duodenal mucosa. CONCLUSION: Abdominal syndrome in SVP is an unfavourable prognostic factor indicating possible severe complications and high risk of glomerulonephritis. Subclinical intestinal involvement presenting as barrier dysfunction may contribute to aggravation of skin vasculitis.
Adolescent↗
2, 4-diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR signals and ulcer in rat jejunum.
BACKGROUND: It has been suggested that one aspect of non-steroidal anti-inflammatory drugs induced intestinal damage is due to either uncoupling of mitochondrial oxidative phosphorylation or inhibition of electron transport. We investigated the latter possibility using electron paramagnetic resonance spectroscopy. RESULTS: Electron paramagnetic studies of NSAIDS on sub-mitochondrial particles revealed that indomethacin, but not with nabumetone, bound to a site near to Complex I and ubiquinone to generate a radical species. Normal rats exhibited prominent [3Fe-4S]ox signals (g approximately 2.01) at 20 K. One hour after indomethacin there was a prominent, intense and broad absorption pattern at (g approximately 2.07) suggesting, appearance of radical species overlapping [3Fe-4S]ox and was unaffected by pretreatment with 2,4 diamino -6-hydroxy pyrimidine. At 24 hrs, when macroscopic ulcers were seen, there was a new signal due to a nitric oxide radical (NO*). In contrast, nabumetone and 2,4 diamino-6-hydroxy pyrimidine pre-treated animals receiving indomethacin exhibited electron paramagnetic resonance spectra identical to those of controls at 24 hrs and neither was associated with small intestinal ulcers. Indomethacin and 2,4 diamino hydroxy pyrimidine pre-treated rats, but not nabumetone, had increased intestinal permeability. CONCLUSION: The results suggest that the in vivo effects of indomethacin modulate the mitochondrial respiratory chain directly at 1 h and 24 h through formation of nitric oxide. NO* appears to play an important role in the late pathogenic stages of NSAID enteropathy and may be the site for targeted treatment to reduce their toxicity.
Animals↗
In siblings with similar genetic susceptibility for inflammatory bowel disease, smokers tend to develop Crohn's disease and non-smokers develop ulcerative colitis.
BACKGROUND AND AIMS: Smoking tobacco has opposite effects on the different forms of inflammatory bowel disease (IBD). It predisposes to the development of Crohn's disease (CD) yet is associated with a reduced incidence of ulcerative colitis (UC). We have studied sib pairs discordant for both smoking and IBD phenotype (UC or CD) to investigate whether smoking determines the type of IBD that develops in individuals with very similar genetic susceptibility. PATIENTS: Smoking habits and disease characteristics were analysed in 242 IBD pedigrees (658 patients). Within this group there were 339 affected sibling pairs of whom 89 were discordant for smoking when diagnosed. RESULTS: Smoking at diagnosis was associated with development of CD (odds ratio (OR) 3.55; 95% confidence limits 2.50-5.02; p<0.001) in all of the familial patients, with increases when analysed for ileocaecal disease, fibrostenosis, and intestinal resection. Smokers were also protected from UC (OR 0.28; 0.2-0.4; p<0.001). Of 89 sibling pairs discordant for smoking at diagnosis, 23 were also discordant for disease type-in 21 of these, CD occurred in the smoker and UC in the non-smoker (OR 10.5; 2.6-92; p<0.0001). CONCLUSIONS: Smoking is a strong environmental risk factor for Crohn's disease and increases the likelihood of needing surgery. However, sib pairs who are discordant for both smoking and IBD type almost always show CD in the smoker and UC in the non-smoker, and so in some cases tobacco consumption acts on IBD genetic predisposition to shift the phenotype from UC towards CD. The explanation of part of the apparent "protective" effect of smoking on sporadic UC may be that the form of IBD that develops in a proportion of smokers is not UC but CD.
Adult↗
Effect of Pentavac and measles-mumps-rubella (MMR) vaccination on the intestine.
BACKGROUND: The safety of infant vaccination has been questioned in recent years. In particular it has been suggested that the measles, mumps, and rubella (MMR) vaccination leads to brain damage manifesting as autism consequent to the development of an "enterocolitis" in the immediate post-vaccination period. AIM: To assess if MMR vaccination is associated with subclinical intestinal inflammation, which is central to the autistic "enterocolitis" theory. METHODS: We studied 109/58 infants, before and two and four weeks after immunisation with Pentavac and MMR vaccines, for the presence of intestinal inflammation (faecal calprotectin). RESULTS: Neither vaccination was associated with any significant increase in faecal calprotectin concentrations. CONCLUSIONS: The failure of the MMR vaccination to cause an intestinal inflammatory response provides evidence against the proposed gut-brain interaction that is central to the autistic "enterocolitis" hypothesis.
Analysis of Variance↗
Intestinal permeability and absorptive capacity in children with portal hypertension.
BACKGROUND: Portal hypertension may affect intestinal function leading to malnutrition in children with liver disease. The aim was to determine whether children with portal hypertension with or without liver disease had impaired absorptive capacity and intestinal barrier function (intestinal permeability) and to ascertain whether these abnormalities related to changes in body composition. METHODS: Twenty-six children with portal hypertension were divided according to aetiology into: Group 1 intrahepatic (n = 15) and Group 2 prehepatic (n = 11). Thirty-five children acted as controls. Carbohydrate absorption and intestinal permeability were assessed using a sugar absorption/permeability test and a variety of anthropometric measurements were obtained. RESULTS: 3-O-methyl-D-glucose, D-xylose and L-rhamnose excretion were significantly reduced in both patient groups compared to controls (P < or = 0.008) and the differential urinary excretion of melibiose/rhamnose (intestinal permeability) was significantly increased in Group 1 only (P < 0.05). Anthropometric measurements showed low Z scores in both groups, but there was no significant (P > 0.05) difference between them. There was no significant correlation between urinary excretion of sugars. anthropometric measurements and energy intake. CONCLUSIONS: Increased portal pressure reduces the absorptive capacity of the small intestine, while liver disease itself leads to increased intestinal permeability.
Adolescent↗
Inflammatory bowel disease and spondylarthropathy.
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Humans↗
A study of the effects of indometacin on liver mitochondria from rats, mice and humans.
BACKGROUND: A part of the mechanism of the gastrointestinal toxicity exhibited by non-steroidal anti-inflammatory drugs is believed to involve the uncoupling of mitochondrial oxidative phosphorylation. Most previous uncoupling studies have used rat liver mitochondria. There is little information on the effects of the drugs on mitochondria from other species. AIM: To study the effect of indometacin on isolated liver mitochondria from rats, mice and humans. METHODS: We studied the effects of indometacin on respiration and adenosine triphosphate synthesis by isolated liver mitochondria from rats, mice and humans. Its effects were compared with those of dinitrophenol, a classical uncoupler. RESULTS: Indometacin uncoupled oxidative phosphorylation at low concentrations (P < 0.05) and inhibited respiration at high concentrations (P < 0.01) in all three species. Adenosine triphosphate synthesis was, however, more sensitive to dinitrophenol or indometacin at lower concentrations in mouse and human compared to rat liver mitochondria (P < 0.05). CONCLUSIONS: The current study shows that indometacin acts as an inhibitory uncoupler in human mitochondria. It also demonstrates that the responses of rat, mouse and human mitochondria to indometacin are broadly similar.
Adenosine Triphosphate↗
Effects of NSAIDs on cryoprobe-induced gastric ulcer healing in rats.
BACKGROUND: Failure of ulcer healing may be critically important to the development of serious gastrointestinal complications in patients on long-term NSAIDs. AIM: To determine the effect of indometacin, celecoxib, a cyclooxygenase-2-specific inhibitor, and nabumetone, a pro-drug, on ulcer healing rates in the rat. METHODS: Gastric ulcers were induced using a cryoprobe. An NSAID or a vehicle control was administered to groups of eight rats for 3 or 6 days (2 mg/kg indometacin, 9 mg/kg celecoxib or 40 mg/kg nabumetone). The ulcer area was measured and epithelial proliferation at the ulcer margins was measured histochemically. The effect of the drugs on intestinal prostaglandin levels was also assessed. RESULTS: The mean ulcer sizes in the four groups on day 3 were comparable. On day 6, control animals and those receiving nabumetone showed significant ulcer healing (P < 0.02), while the mean ulcer sizes in the indometacin (P < 0.01) and celecoxib (P < 0.02) groups were significantly larger than those in the control group. Higher doses of nabumetone (160 mg/kg), however, impaired healing. Intestinal prostaglandins were reduced (P < 0.01) only in indometacin-treated animals. The epithelial proliferation index was significantly lower among indometacin- (P=0.02) and celecoxib-treated (P=0.03) animals compared to controls at day 3. CONCLUSIONS: Celecoxib and indometacin both decreased the epithelial proliferative response and delayed healing of cryoprobe-induced gastric ulcers. In contrast, nabumetone impaired ulcer healing only at very high doses.
Animals↗
Epidemiology and differential diagnosis of NSAID-induced injury to the mucosa of the small intestine.
Non-steroidal anti-inflammatory drugs cause small-bowel inflammation in about 60% of patients receiving these drugs long-term. The inflammation is associated with small intestinal bleeding, protein loss, ulcers and occasionally strictures. Treatment options for NSAID enteropathy include metronidazole, sulphasalazine and misoprostol, and some patients may require surgery. The diagnosis of NSAID enteropathy is not always straightforward. It is especially difficult to differentiate it from the ileitis associated with spondylarthropathy and, at times, that of Crohn's disease. An investigational algorithm is suggested for this purpose. In the last decade a number of small-bowel diseases have been identified, where none were thought to exist, because of the increasing use of enteroscopy and new sensitive tests for intestinal inflammation. Optimal treatments of these conditions are still to be studied.
Algorithms↗
Fecal calprotectin: a significant step in the noninvasive assessment of intestinal inflammation.
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Antifungal Agents↗
Are cyclooxygenase 2 inhibitors free of gastrointestinal side effects?
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Cyclooxygenase 2↗
Selective inhibition of COX-2 in humans is associated with less gastrointestinal injury: a comparison of nimesulide and naproxen.
BACKGROUND: Selective inhibitors of cyclooxygenase (COX)-2 may provoke less gastric damage and platelet inhibition than conventional non-steroidal anti-inflammatory drugs. AIMS: We compared the biochemical and gastrointestinal effects of nimesulide, a potent and selective COX-2 inhibitor, with naproxen which exhibits no selectivity. SUBJECTS: Thirty six healthy volunteers were randomised to nimesulide 100 mg or naproxen 500 mg twice daily for two weeks in a double blind, crossover study with a washout between treatments. METHODS: Gastrointestinal side effects were assessed by endoscopy, and by estimation of small intestinal absorption-permeability and inflammation. Comparisons were made between variables at the end of each treatment phase. RESULTS: Nimesulide caused significantly less gastric injury using the modified Lanza score (p<0.001) as well as reduced duodenum injury (p=0.039). Nimesulide had lower visual analogue scores (VAS) for haemorrhage and erosive lesions in the stomach (p<0.001) and for mucosal injection in the duodenum (p=0.039). Naproxen increased excretion of calprotectin, a marker of intestinal inflammation (5.5 (1.2) to 12.1 (2.1) mg/l) while nimesulide had no effect (treatment difference p=0.03). Naproxen abolished platelet aggregation to arachidonic acid and suppressed serum thromboxane B(2) (TXB(2)) by 98%, indices of COX-1 activity. In contrast, nimesulide had no significant effect on platelet aggregation, although it reduced serum TXB(2) by 29%. Production of prostaglandin E(2) and prostacyclin by gastric biopsies, also COX-1 dependent, was inhibited by naproxen, but not by nimesulide. COX-2 activity, determined as endotoxin induced prostaglandin E(2) formation in plasma, was markedly suppressed by both treatments. INTERPRETATION: Nimesulide has preferential selectivity for COX-2 over COX-1 in vivo at full therapeutic doses and induces less gastrointestinal damage than that seen with naproxen in the short term.
Adolescent↗
COX-2 inhibitors and the gastrointestinal tract.
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Animals↗
Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma.
BACKGROUND AND AIMS: Testing for faecal occult blood has become an accepted technique of non-invasive screening for colorectal neoplasia but lack of sensitivity remains a problem. The aim of this study was to compare the sensitivity and specificity of faecal calprotectin and faecal occult blood in patients with colorectal cancer and colonic polyps. METHODS: Faecal calprotectin and occult blood were assessed in 62 patients with colorectal carcinoma and 233 patients referred for colonoscopy. The range of normality for faecal calprotectin (0.5-10.5 mg/l) was determined from 96 healthy subjects. RESULTS: Median faecal calprotectin concentration in the 62 patients with colorectal carcinoma (101 mg/l, 95% confidence interval (CI) 57-133) differed significantly from normal (2.3 mg/l, 95% CI 1.6-5.0) with 90% of patients having elevated levels (normal <10 mg/l) whereas only 36/62 (58%) had positive faecal occult bloods. There was no significant difference in faecal calprotectin levels when considering location or Dukes' staging of tumour. Percentage positivity of faecal occult bloods was significantly higher for Dukes' stage C and D cancers compared with Dukes' A and B. In the colonoscopy group, 29 patients with adenomatous polyps were detected in whom the median faecal calprotectin was 12 mg/l (95% CI 2.9-32). Sensitivity for detection of adenomatous polyps was 55% using the calprotectin method and 10% using faecal occult blood testing. The overall sensitivity and specificity of calprotectin for colorectal cancer and adenomatous polyps as a combined group was 79% and 72%, respectively, compared with a sensitivity and specificity of faecal occult blood of 43% and 92%. CONCLUSIONS: Faecal calprotectin is a simple and sensitive non-invasive marker of colorectal cancer and adenomatous polyps. It is more sensitive than faecal occult blood tests for detection of colorectal neoplasia at the cost of a somewhat lower specificity.
Adenoma↗
Non-invasive investigation of inflammatory bowel disease.
The assessment of inflammatory activity in intestinal disease in man can be done using a variety of different techniques. These range from the use of non-invasive acute phase inflammatory markers measured in plasma such as C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) (both of which give an indirect assessment of disease activity) to the direct assessment of disease activity by intestinal biopsy performed during endoscopy in association with endoscopic scoring systems. Both radiology and endoscopy are conventional for the diagnosis of inflammatory bowel disease (IBD). However these techniques have severe limitations when it comes to assessing functional components of the disease such as activity and prognosis. Here we briefly review the value of two emerging intestinal function tests. Intestinal permeability, although ideally suited for diagnostic screening for small bowel Crohn's disease, appears to give reliable predictive data for imminent relapse of small bowel Crohn's disease and it can be used to assess responses to treatment. More significantly it is now clear that single stool assay of neutrophil specific proteins (calprotectin, lactoferrin) give the same quantitative data on intestinal inflammation as the 4 day faecal excretion of 111Indium labelled white cells. Faecal calprotectin is shown to be increased in over 95% of patients with IBD and correlates with clinical disease activity. It reliably differentiates between patients with IBD and irritable bowel syndrome. More importantly, at a given faecal calprotectin concentration in patients with quiescent IBD, the test has a specificity and sensitivity in excess of 85% in predicting clinical relapse of disease. This suggests that relapse of IBD is closely related to the degree of intestinal inflammation and suggests that targeted treatment at an asymptomatic stage of the disease may be indicated.
Biomarkers↗