Background: Enquiries among patients on the one hand and experimental and observational studies o... more Background: Enquiries among patients on the one hand and experimental and observational studies on the other suggest an influence of stress on inflammatory bowel diseases (IBD). However, since this influence remains hypothetical, further research is essential. We aimed to devise recommendations for future investigations in IBD by means of scrutinizing previously applied methodology. Methods: We critically reviewed prospective clinical studies on the effect of psychological stress on IBD. Eligible studies were searched by means of the PubMed electronic library and through checking the bibliographies of located sources. Results: We identified 20 publications resulting from 18 different studies. Sample sizes ranged between 10 and 155 participants. Study designs in terms of patient assessment, control variables, and applied psychometric instruments varied substantially across studies. Methodological strengths and weaknesses were irregularly dispersed. Thirteen studies reported significa...
Background:Thromboxanes, prostaglandins, reactive oxygen metabolites and pro‐inflammatory cytokin... more Background:Thromboxanes, prostaglandins, reactive oxygen metabolites and pro‐inflammatory cytokines are produced in excess in inflammatory bowel disease. Preliminary reports suggest that ridogrel, a thromboxane synthesis inhibitor and receptor blocker, may have therapeutic benefits in ulcerative colitis.Aims:To investigate the anti‐inflammatory profile of ridogrel.Methods:The effects of ridogrel on the production of eicosanoids, reactive oxygen metabolites and cytokines by cultured inflamed colorectal mucosal biopsies were made using ELISA and chemiluminescence, reactive oxygen metabolite generation in a cell‐free system, and platelet activation using flow cytometry. The effects of oral ridogrel on mucosal release of eicosanoids in two patients with active ulcerative colitis were assessed using rectal dialysis.Results:Ridogrel significantly reduced the release of thromboxane B2, but not prostaglandin E2 or tumour necrosis factor‐α, from biopsies (P < 0.01 for 10 μM ridogrel). Rid...
Helicobacter pylori infection has been associated with stimulation of gastric mucosal reactive ox... more Helicobacter pylori infection has been associated with stimulation of gastric mucosal reactive oxygen metabolite production. To provide further evidence of a causal relationship we looked for a dose-response relationship. We studied antral biopsy material from 110 patients. Quantitative H. pylori assessments were made using histologic and microbiologic methods. Reactive oxygen metabolite production was measured by luminol-dependent chemiluminescence. The usefulness of timed urease test colour changes as a guide to infective load was assessed. There was a positive association between mucosal reactive oxygen metabolite production and histologic (p = 0.002, n = 69) and microbiologic (Spearman&#39;s R = +0.6, p = 0.05, n = 18) quantitative H. pylori assessments. H. pylori infective load varied markedly over small areas (coefficient of repeatability of paired cultures (in colony-forming units/mg) = 1.9 x 10(6). Urease test timing correlated with histologic (p = 0.01) and microbiologic (p = 0.03) H. pylori quantitation. Histologically assessed mucosal damage was related to quantitative H. pylori assessment and to mucosal reactive oxygen metabolite production (p = 0.0001). These results support the hypothesis that H. pylori stimulates gastric mucosal reactive oxygen metabolite production and that this phenomenon is of pathogenic importance.
Background:Reactive oxygen species may be pathogenic in ulcerative colitis. Oral iron supplements... more Background:Reactive oxygen species may be pathogenic in ulcerative colitis. Oral iron supplements anecdotally exacerbate inflammatory bowel disease and iron levels are elevated in the inflamed mucosa. Mucosal iron may enhance hydroxyl ion production via Fenton chemistry. Conversely, the iron chelator, desferrioxamine, is reportedly beneficial in Crohn’s disease.Aims:To assess the in vitro effects of exogenous iron and of iron chelators on the production of reactive oxygen species by colonic biopsies from normal control subjects and patients with ulcerative colitis.Methods:Luminol‐amplified chemiluminescence was used to measure mucosal reactive oxygen species production both before and after addition in vitro of ferric citrate (100 μM), desferrioxamine (1 m M) and 1,10‐phenanthroline (1 m M).Results:Ferric citrate had no effect on the chemiluminescence produced by human colonic mucosa. However, desferrioxamine and phenanthroline reduced chemiluminescence by 47% (n=7, P=0.018) and by 26% (n=10, P=0.005), respectively, in inactive ulcerative colitis, and by 44% (n=9, P=0.008) and 42% (n=11, P=0.006) in active disease.Conclusion:The lack of effect of ferric citrate suggests that sufficient free iron is already present in inflamed biopsies to drive the Fenton reaction maximally. The effects of desferrioxamine and 1,10‐phenanthroline on the chemiluminescence of biopsies from patients with ulcerative colitis suggest that a clinical trial of topical iron chelation in active disease is indicated.
To assess the incidence of ulcerative colitis and proctitis in a defined migrant population, a re... more To assess the incidence of ulcerative colitis and proctitis in a defined migrant population, a retrospective, epidemiological community study was performed in the London Borough of Tower Hamlets from 1972 to 1989. The population of 164,000 includes 28,000 Bangladeshis. Potential cases were identified from hospital departments of pathology and medical records. There were 107 cases of ulcerative colitis in Europeans and 5 in Bangladeshis. There were 74 and 2 cases of proctitis in these communities, respectively. The mean standardised incidence of ulcerative colitis in Bangladeshis (1.8 cases/10(5)/year) was marginally lower than in Europeans (6.2 cases/10(5)/year, Z = 0.7, n.s.). The mean standardised incidence of proctitis in Bangladeshis was 0.6 cases/10(5)/year and in Europeans 3.2 cases/10(5)/year (Z = 0.6 n.s.). Anatomical extent of colitis was similar in all ethnic communities, although complications were less likely in minority groups. These findings suggest that the incidence of ulcerative colitis and proctitis in Bangladeshis, in Britain, is amongst the lowest in the world.
... 5 Wheeler SC, Marion JF, Present DH. Medical therapy, not surgery, is the appropriate first l... more ... 5 Wheeler SC, Marion JF, Present DH. Medical therapy, not surgery, is the appropriate first line treatment for Crohn's enterovesical fistula. ... 9 Munkholm P, Langholz E, Davidsen N, Binder V. Frequency of glucocorticoid resistance and dependency in Crohn's disease. ...
A retrospective epidemiological study of abdominal tuberculosis in a defined population in the Lo... more A retrospective epidemiological study of abdominal tuberculosis in a defined population in the London Borough of Tower Hamlets was conducted between January 1985 and 31 December 1989. The total population of 163,900 included a mean of 20,732 Bangladeshis. Of the 13 cases diagnosed 8 were Bangladeshi, with equal involvement of the peritoneum and intestine. The crude incidence in the Bangladeshi community was 7.7 cases/10(5)/year, which was significantly higher than that in Europeans (0.3 cases/10(5)/year, chi 2 with Yate&amp;amp;amp;amp;#39;s correction = 14.0 P &amp;amp;amp;amp;lt; 0.001). The highest age-specific incidence was amongst those aged 16-20 years and 41-45 years. Most patients had a laparotomy or peritoneal biopsy to confirm the diagnosis. The response to therapy was good. Only 62% of cases were notified. This study confirms the importance of tuberculosis in the differential diagnosis of abdominal symptoms in Bangladeshi patients.
A single-pass perfusion system was used in conscious restrained rats to measure changes in water ... more A single-pass perfusion system was used in conscious restrained rats to measure changes in water and electrolyte transport and in protein and deoxyribonucleic acid output after perfusing 5-15-mM solutions of sulfated or nonsulfated bile acids through the colon. Perfusion with 5 mM nonsulfated deoxycholic acid or chenodeoxycholic acid changed net water and sodium absorption to net secretion, provoked marked increases in protein and DNA output into the perfusion effluent, and caused microscopic mucosal damage. In contrast, perfusion with 5 and 15 mM sulfated deoxycholic acid or with 5 mM sulfated chenodeoxycholic acid had no effect on water and electrolyte transport and caused only modest changes in protein and DNA output. To see whether or not sulfated bile acid could prevent the effect of its nonsulfated parent compound on colonic structure and function, perfusion with a mixture of 5 mM nonsulfated and 10 mM sulfated deoxycholic acid was performed. This produced net secretion of water and sodium together with less marked increases of protein and deoxyribonucleic acid output and less pronounced microscopic mucosal damage than was seen after 5 mM nonsulfated deoxycholic acid alone. Finally, 5 mM nonsulfated cholic acid had no effect on water or sodium transport, but 5 mM sulfated cholic acid, with one alpha-hydroxyl group masked and two alpha-hydroxyl groups "exposed," reduced water transport. These results suggest that sulfation prevents the cathartic effect of alpha-dihydroxyl bile acids in the colon.
In recent years there has been increasing recognition by doctors as well as patients that psychol... more In recent years there has been increasing recognition by doctors as well as patients that psychological stress can worsen the course of inflammatory bowel disease (IBD).1 3 In this issue, Bitton et al (see page 1386) report that the way in which some patients cope increases the risk of ...
There is increasing evidence that psychological stress and associated mood disorders are linked w... more There is increasing evidence that psychological stress and associated mood disorders are linked with, and can adversely affect the course of inflammatory bowel disease (IBD). Of 11 longitudinal studies of the effects of stress or depression on the course of IBD, most suggested that stress worsened IBD, the rest giving either negative or inconclusive results. If stress does have an adverse effect on the natural history of IBD, then measures which reduce stress should help symptoms and activity of IBD. Unfortunately, because of methodological difficulties inherent in undertaking appropriately targeted and blinded trials, good data about the effects on IBD of interventions aimed to ameliorate stress and mood disorders are limited. Emerging trial evidence supports the suggestion that psychologically orientated therapy may ameliorate IBD-associated mood disorders, but there is no strong data yet to indicate that stress management has a beneficial effect on the activity or course of IBD. More rigorous assessments are needed of the relation between psychological state and activity of IBD, and of the potential benefits of stress-reducing measures in IBD.
Background: Enquiries among patients on the one hand and experimental and observational studies o... more Background: Enquiries among patients on the one hand and experimental and observational studies on the other suggest an influence of stress on inflammatory bowel diseases (IBD). However, since this influence remains hypothetical, further research is essential. We aimed to devise recommendations for future investigations in IBD by means of scrutinizing previously applied methodology. Methods: We critically reviewed prospective clinical studies on the effect of psychological stress on IBD. Eligible studies were searched by means of the PubMed electronic library and through checking the bibliographies of located sources. Results: We identified 20 publications resulting from 18 different studies. Sample sizes ranged between 10 and 155 participants. Study designs in terms of patient assessment, control variables, and applied psychometric instruments varied substantially across studies. Methodological strengths and weaknesses were irregularly dispersed. Thirteen studies reported significa...
Background:Thromboxanes, prostaglandins, reactive oxygen metabolites and pro‐inflammatory cytokin... more Background:Thromboxanes, prostaglandins, reactive oxygen metabolites and pro‐inflammatory cytokines are produced in excess in inflammatory bowel disease. Preliminary reports suggest that ridogrel, a thromboxane synthesis inhibitor and receptor blocker, may have therapeutic benefits in ulcerative colitis.Aims:To investigate the anti‐inflammatory profile of ridogrel.Methods:The effects of ridogrel on the production of eicosanoids, reactive oxygen metabolites and cytokines by cultured inflamed colorectal mucosal biopsies were made using ELISA and chemiluminescence, reactive oxygen metabolite generation in a cell‐free system, and platelet activation using flow cytometry. The effects of oral ridogrel on mucosal release of eicosanoids in two patients with active ulcerative colitis were assessed using rectal dialysis.Results:Ridogrel significantly reduced the release of thromboxane B2, but not prostaglandin E2 or tumour necrosis factor‐α, from biopsies (P < 0.01 for 10 μM ridogrel). Rid...
Helicobacter pylori infection has been associated with stimulation of gastric mucosal reactive ox... more Helicobacter pylori infection has been associated with stimulation of gastric mucosal reactive oxygen metabolite production. To provide further evidence of a causal relationship we looked for a dose-response relationship. We studied antral biopsy material from 110 patients. Quantitative H. pylori assessments were made using histologic and microbiologic methods. Reactive oxygen metabolite production was measured by luminol-dependent chemiluminescence. The usefulness of timed urease test colour changes as a guide to infective load was assessed. There was a positive association between mucosal reactive oxygen metabolite production and histologic (p = 0.002, n = 69) and microbiologic (Spearman&#39;s R = +0.6, p = 0.05, n = 18) quantitative H. pylori assessments. H. pylori infective load varied markedly over small areas (coefficient of repeatability of paired cultures (in colony-forming units/mg) = 1.9 x 10(6). Urease test timing correlated with histologic (p = 0.01) and microbiologic (p = 0.03) H. pylori quantitation. Histologically assessed mucosal damage was related to quantitative H. pylori assessment and to mucosal reactive oxygen metabolite production (p = 0.0001). These results support the hypothesis that H. pylori stimulates gastric mucosal reactive oxygen metabolite production and that this phenomenon is of pathogenic importance.
Background:Reactive oxygen species may be pathogenic in ulcerative colitis. Oral iron supplements... more Background:Reactive oxygen species may be pathogenic in ulcerative colitis. Oral iron supplements anecdotally exacerbate inflammatory bowel disease and iron levels are elevated in the inflamed mucosa. Mucosal iron may enhance hydroxyl ion production via Fenton chemistry. Conversely, the iron chelator, desferrioxamine, is reportedly beneficial in Crohn’s disease.Aims:To assess the in vitro effects of exogenous iron and of iron chelators on the production of reactive oxygen species by colonic biopsies from normal control subjects and patients with ulcerative colitis.Methods:Luminol‐amplified chemiluminescence was used to measure mucosal reactive oxygen species production both before and after addition in vitro of ferric citrate (100 μM), desferrioxamine (1 m M) and 1,10‐phenanthroline (1 m M).Results:Ferric citrate had no effect on the chemiluminescence produced by human colonic mucosa. However, desferrioxamine and phenanthroline reduced chemiluminescence by 47% (n=7, P=0.018) and by 26% (n=10, P=0.005), respectively, in inactive ulcerative colitis, and by 44% (n=9, P=0.008) and 42% (n=11, P=0.006) in active disease.Conclusion:The lack of effect of ferric citrate suggests that sufficient free iron is already present in inflamed biopsies to drive the Fenton reaction maximally. The effects of desferrioxamine and 1,10‐phenanthroline on the chemiluminescence of biopsies from patients with ulcerative colitis suggest that a clinical trial of topical iron chelation in active disease is indicated.
To assess the incidence of ulcerative colitis and proctitis in a defined migrant population, a re... more To assess the incidence of ulcerative colitis and proctitis in a defined migrant population, a retrospective, epidemiological community study was performed in the London Borough of Tower Hamlets from 1972 to 1989. The population of 164,000 includes 28,000 Bangladeshis. Potential cases were identified from hospital departments of pathology and medical records. There were 107 cases of ulcerative colitis in Europeans and 5 in Bangladeshis. There were 74 and 2 cases of proctitis in these communities, respectively. The mean standardised incidence of ulcerative colitis in Bangladeshis (1.8 cases/10(5)/year) was marginally lower than in Europeans (6.2 cases/10(5)/year, Z = 0.7, n.s.). The mean standardised incidence of proctitis in Bangladeshis was 0.6 cases/10(5)/year and in Europeans 3.2 cases/10(5)/year (Z = 0.6 n.s.). Anatomical extent of colitis was similar in all ethnic communities, although complications were less likely in minority groups. These findings suggest that the incidence of ulcerative colitis and proctitis in Bangladeshis, in Britain, is amongst the lowest in the world.
... 5 Wheeler SC, Marion JF, Present DH. Medical therapy, not surgery, is the appropriate first l... more ... 5 Wheeler SC, Marion JF, Present DH. Medical therapy, not surgery, is the appropriate first line treatment for Crohn's enterovesical fistula. ... 9 Munkholm P, Langholz E, Davidsen N, Binder V. Frequency of glucocorticoid resistance and dependency in Crohn's disease. ...
A retrospective epidemiological study of abdominal tuberculosis in a defined population in the Lo... more A retrospective epidemiological study of abdominal tuberculosis in a defined population in the London Borough of Tower Hamlets was conducted between January 1985 and 31 December 1989. The total population of 163,900 included a mean of 20,732 Bangladeshis. Of the 13 cases diagnosed 8 were Bangladeshi, with equal involvement of the peritoneum and intestine. The crude incidence in the Bangladeshi community was 7.7 cases/10(5)/year, which was significantly higher than that in Europeans (0.3 cases/10(5)/year, chi 2 with Yate&amp;amp;amp;amp;#39;s correction = 14.0 P &amp;amp;amp;amp;lt; 0.001). The highest age-specific incidence was amongst those aged 16-20 years and 41-45 years. Most patients had a laparotomy or peritoneal biopsy to confirm the diagnosis. The response to therapy was good. Only 62% of cases were notified. This study confirms the importance of tuberculosis in the differential diagnosis of abdominal symptoms in Bangladeshi patients.
A single-pass perfusion system was used in conscious restrained rats to measure changes in water ... more A single-pass perfusion system was used in conscious restrained rats to measure changes in water and electrolyte transport and in protein and deoxyribonucleic acid output after perfusing 5-15-mM solutions of sulfated or nonsulfated bile acids through the colon. Perfusion with 5 mM nonsulfated deoxycholic acid or chenodeoxycholic acid changed net water and sodium absorption to net secretion, provoked marked increases in protein and DNA output into the perfusion effluent, and caused microscopic mucosal damage. In contrast, perfusion with 5 and 15 mM sulfated deoxycholic acid or with 5 mM sulfated chenodeoxycholic acid had no effect on water and electrolyte transport and caused only modest changes in protein and DNA output. To see whether or not sulfated bile acid could prevent the effect of its nonsulfated parent compound on colonic structure and function, perfusion with a mixture of 5 mM nonsulfated and 10 mM sulfated deoxycholic acid was performed. This produced net secretion of water and sodium together with less marked increases of protein and deoxyribonucleic acid output and less pronounced microscopic mucosal damage than was seen after 5 mM nonsulfated deoxycholic acid alone. Finally, 5 mM nonsulfated cholic acid had no effect on water or sodium transport, but 5 mM sulfated cholic acid, with one alpha-hydroxyl group masked and two alpha-hydroxyl groups "exposed," reduced water transport. These results suggest that sulfation prevents the cathartic effect of alpha-dihydroxyl bile acids in the colon.
In recent years there has been increasing recognition by doctors as well as patients that psychol... more In recent years there has been increasing recognition by doctors as well as patients that psychological stress can worsen the course of inflammatory bowel disease (IBD).1 3 In this issue, Bitton et al (see page 1386) report that the way in which some patients cope increases the risk of ...
There is increasing evidence that psychological stress and associated mood disorders are linked w... more There is increasing evidence that psychological stress and associated mood disorders are linked with, and can adversely affect the course of inflammatory bowel disease (IBD). Of 11 longitudinal studies of the effects of stress or depression on the course of IBD, most suggested that stress worsened IBD, the rest giving either negative or inconclusive results. If stress does have an adverse effect on the natural history of IBD, then measures which reduce stress should help symptoms and activity of IBD. Unfortunately, because of methodological difficulties inherent in undertaking appropriately targeted and blinded trials, good data about the effects on IBD of interventions aimed to ameliorate stress and mood disorders are limited. Emerging trial evidence supports the suggestion that psychologically orientated therapy may ameliorate IBD-associated mood disorders, but there is no strong data yet to indicate that stress management has a beneficial effect on the activity or course of IBD. More rigorous assessments are needed of the relation between psychological state and activity of IBD, and of the potential benefits of stress-reducing measures in IBD.
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