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D S Rampton

Publications and source records attributed to D S Rampton.

At least 19 recordsLinked to original sources
PubMed1992

Chemiluminescence assay of mucosal reactive oxygen metabolites in inflammatory bowel disease.

Previous studies suggesting increased reactive oxygen metabolite (ROM) production in inflammatory bowel disease have been restricted to peripheral blood and isolated intestinal phagocytes. In the current study, chemiluminescence and the effect of various scavengers, enzymes, and enzyme inhibitors were used to show that ROMs account for the increased production of oxidants by colorectal mucosal biopsy specimens in inflammatory bowel disease. Luminol-amplified chemiluminescence was increased in active ulcerative colitis [macroscopic grade 1: 25 photons.mg-1.min.10(-3) (median), 8-47 (95% confidence intervals), n = 40; grade 2: 89, 65-156, n = 30; grade 3: 247, 133-562, n = 13] and Crohn's disease [mild: 9, 3-84, n = 6; severe: 105, 25-789 (range), n = 5] compared with normal-looking mucosa (ulcerative colitis: 0.8, 0.4-1.4, n = 22, P less than 0.01; Crohn's disease: 0.8, 0.1-2, n = 6, P less than 0.05) and controls (0.6, 0.04-1.4, n = 52, P less than 0.01). In ulcerative colitis, luminol chemiluminescence correlated with microscopic inflammation (Spearman's p = 0.74, P = 0.0001) and was decreased by sodium azide (-89%, P less than 0.05), taurine (-31%, P less than 0.05), catalase (-23%, P less than 0.05), and dimethyl sulfoxide (-29%, P less than 0.05). Superoxide dismutase and oxypurinol decreased lucigenin chemiluminescence in ulcerative colitis by -63% (P less than 0.05) and -27% (P less than 0.05), respectively. Luminol chemiluminescence correlated with lucigenin chemiluminescence (Spearman's rho = 0.72, P = 0.003). These results suggest that neutrophil-derived oxidants (superoxide, hydrogen peroxide, hydroxyl radical, and hypochlorite) are generated in colorectal mucosa in active inflammatory bowel disease and support the hypothesis that production of such metabolites by neutrophils is of major pathogenetic importance.

Acridines↗
PubMed1992

Verapamil inhibits in-vitro leucotriene B4 release by rectal mucosa in active ulcerative colitis.

Increased mucosal eicosanoid synthesis occurs in active ulcerative colitis; suppression of the synthesis of pro-inflammatory leucotrienes could be therapeutically useful. Neutrophil 5-lipoxygenase is calcium-dependent. In this study, the effect of the calcium channel antagonist, verapamil, on the release of eicosanoids by colitic rectal mucosal biopsies has been examined. Verapamil in therapeutic concentration (5 micrograms/ml, 10(-5) M) reduced leucotriene B4 release from actively inflamed rectal mucosa by 30% (from 60 (5.0 S.E.M.) ng/g wet weight/20 min without, to 42 (5.7 S.E.M.) with verapamil, P less than 0.05), but had no effect on leucotriene B4 release by rectal biopsies taken from patients with quiescent ulcerative colitis (39 (2.8 S.E.M.) ng/g wet weight/20 min without, and 43 (5.0 S.E.M.) with verapamil). Verapamil did not affect mucosal prostaglandin E2 release. The results suggest that, in active ulcerative colitis, verapamil inhibits mucosal 5-lipoxygenase activity and warrants therapeutic evaluation.

Biopsy↗
PubMed1992

Circulating antibodies to heat-shock protein 60 in Crohn's disease and ulcerative colitis.

Heat-shock proteins (HSPs) are highly conserved immunogenic intracellular molecules that are induced by inflammatory mediators and may induce autoimmune phenomena in vivo. We have recently demonstrated the increased expression of HSP-60 in the colonocytes of patients with ulcerative colitis. To study further the role of HSP-60 in inflammatory bowel disease, we have now measured antibodies to recombinant mycobacterial HSP-65 (a member of the HSP-60 family) in patients with Crohn's disease, ulcerative colitis, healthy volunteers and, as disease controls, patients with confirmed bacterial diarrhoea. In comparison with healthy controls (n = 20; median level of 89 ELISA units; range 24-292), serum IgA HSP-60 antibodies were elevated in Crohn's disease (n = 21; 157; 57-364; P < 0.05) and active ulcerative colitis (n = 16; 188; 58-373; P < 0.01) but not bacterial diarrhoea (n = 10; 106; 51-285). Increased IgA HSP-60 antibody levels in patients with inflammatory bowel disease may occur as the result of HSP release from injured gut epithelium; alternatively, increased intestinal permeability could facilitate mucosal access of luminal antigens and the generation of cross-reactive anti-bacterial HSP antibodies.

Antibodies↗
PubMed1992

Mucosal reactive oxygen metabolite production in duodenal ulcer disease.

To investigate the hypothesis that reactive oxygen metabolites are important in the pathophysiology of duodenal ulcer disease, their production by duodenal mucosal biopsy specimens was measured using luminol and lucigenin amplified chemiluminescence. Luminol chemiluminescence, expressed as background corrected median photon emission/mg/min x 10(3) (95% confidence intervals), was increased in duodenal inflammation as assessed macroscopically: ulcers 20.3 (4.8 to 51.3), n = 29; severe duodenitis 13.9 (6.6 to 75.3), n = 16; mild duodenitis 0.0 (-0.5 to 0.8), n = 56; controls -0.8 (-1.3 to -0.1), n = 41; p = 0.0001, Kruskal-Wallis) and microscopically: severe 17.0 (9.3 to 51.3), n = 12; moderate 0.3 (-2.8 to 5.8), n = 17; mild -0.1 (-1.8 to 1.0), n = 17; controls -0.8 (-1.6 to 0.0), n = 15; (p = 0.0001). Luminol chemiluminescence was directly related to both the macroscopic and microscopic severity of duodenal damage (Spearman's R = + 0.53, + 0.55 respectively, both p = 0.0001), to histochemical assessment (myeloperoxidase activity) of neutrophil infiltration (R = + 0.63; p = 0.04), and to lucigenin chemiluminescence (R = + 0.56, p = 0.0002). Luminol chemiluminescence was inhibited by sodium azide (-80%), catalase (-73%), and dimethyl sulphoxide (-24%). Superoxide dismutase inhibited lucigenin more than luminol dependent chemiluminescence (-61% and -7% respectively, p < 0.05). Within disease groups, Helicobacter pylori antral infection was associated with increased duodenal chemiluminescence, whereas smoking, alcohol, and use of NSAIDs or H2 blockers had no influence. Their disease related generation in duodenal mucosa supports a role for reactive oxygen metabolites in the pathogenesis of duodenitis and duodenal ulcer. These metabolites might include superoxide, hydrogen peroxide, hydroxyl, and products of myeloperoxidase activity.

Adult↗
PubMed1992

Circulating von Willebrand factor in inflammatory bowel disease.

Raised circulating von Willebrand factor is a recognised marker of vascular injury. To evaluate the role of vascular injury in the pathogenesis of inflammatory bowel disease, serum von Willebrand factor in Crohn's disease, ulcerative colitis, confirmed bacterial diarrhoea, and healthy subjects was measured. von Willebrand factor values were raised in 9/14 patients (p = 0.007) with active Crohn's disease, 15/28 (p = 0.0004) with inactive Crohn's disease, 16/23 (p = 0.0003) with active ulcerative colitis, 9/27 (p = 0.04) with inactive ulcerative colitis, and 15/17 (p = 0.0001) patients with bacterial diarrhoea. Serum von Willebrand factor was unrelated to disease activity in Crohn's disease but was significantly raised in active (p = 0.02) compared with inactive ulcerative colitis. In contrast to controls, the detection of von Willebrand factor from inflammatory bowel disease sera and that from fractured endothelial cells was significantly inhibited by the reducing agent, dithiothreitol, suggesting the presence of an additional dithiothreitol sensitive form of the molecule derived from injured endothelial cells in inflammatory bowel disease. That serum von Willebrand factor is raised in quiescent as well as active Crohn's disease is compatible with the proposal that vascular injury is a fundamental abnormality in this disorder. The raised von Willebrand factor values in active inflammatory bowel disease and bacterial diarrhoea could be caused by either vascular injury, occurring secondary to bowel inflammation, or to an acute phase response resulting from endothelial cell stimulation by mediators released during the inflammatory process. Raised circulating von Willebrand factor could contribute to the increased risk of thrombosis associated with active inflammatory bowel disease.

Bacterial Infections↗
PubMed1992

Anti-neutrophil antibodies in inflammatory bowel disease: prevalence and diagnostic role.

Anti-neutrophil antibodies have been shown in sera from patients with a variety of inflammatory diseases. Those reacting with components of neutrophil cytoplasm are associated with systemic vasculitis. Both nuclear and perinuclear staining patterns on human neutrophils have been reported using sera from patients with inflammatory bowel disease. We have evaluated the reactivity against human neutrophils of sera from 100 patients with inflammatory bowel disease, 14 disease controls, and 20 normal volunteers. Altogether 27/50 (54%) sera from patients with ulcerative colitis contained antibodies that reacted with cytospun ethanol fixed neutrophils compared with 5/50 (10%) from Crohn's disease (p less than 0.001) and 0/34 control sera (p less than 0.001). All seven sera from patients with proctitis alone were negative (p less than 0.01). There was no correlation between presence or titre of anti-neutrophil antibodies and either disease activity or treatment. Positive sera gave three different staining patterns on human neutrophils. The predominant pattern was perinuclear (17/32); 12 sera gave a cytoplasmic and three a homogeneous nuclear staining pattern. None of the patients or the controls had antibodies to myeloperoxidase, elastase, or serine proteinase 3, all of which are recognised by anti-neutrophil cytoplasmic antibodies. Only 2/27 sera positive by indirect immunofluorescence reacted with an extract of neutrophil primary granules. In conclusion, anti-neutrophil antibodies occur more commonly in ulcerative colitis than in Crohn's disease or control subjects and the anti-neutrophil antibodies found in inflammatory bowel disease are different from those associated with vasculitis.

Adult↗
PubMed1992

Crohn's disease in Bangladeshis and Europeans in Britain: an epidemiological comparison in Tower Hamlets.

The incidence of Crohn's disease in a defined Bangladeshi community was assessed in a retrospective, epidemiological study in the London Borough of Tower Hamlets from 1972 to 1989. The borough population of 164,000 includes over 28,000 Bangladeshis. Potential cases were identified from hospital pathology and medical records. There were 99 cases of Crohn's disease during the study period, of which five were Bangladeshi. The mean standardized incidence in Bangladeshis was 1.2/10(5)/year in the 1970s and 2.3/10(5)/year in the 1980s compared with 3.8/10(5)/year and 4.1/10(5)/year in Europeans, and 4.6/10(5)/year and 5.4/10(5)/year in West Indians, respectively. None of the changes with time was statistically significant. There were no cases amongst Hindus. The relative risk to Europeans, compared to Bangladeshis, was 2.5 during the 1970s and 2.0 in the 1980s. The difference between European incidence and that of other ethnic groups was not statistically significant; however, the number of Bangladeshi cases was small (five), and diminishes the power of the study. The apparent similarity of the incidences of Crohn's disease in Bangladeshis and Europeans contrasts with findings in other South Asians. Further investigations of the differences in incidence of Crohn's disease in South Asians is needed.

Adolescent↗
PubMed1992

Low incidence of ulcerative colitis and proctitis in Bangladeshi migrants in Britain.

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.

Age Factors↗
PubMed1992

Effects of indomethacin and misoprostol on renal function in healthy volunteers.

We have examined the effects on renal function of indomethacin and misoprostol, alone and in combination. Eight healthy volunteers took indomethacin 50 mg tds for one week, and indomethacin plus misoprostol (a synthetic PGE1 analogue) 200 micrograms qds for one week in a crossover design. A separate group (n = 5) took misoprostol alone for one week. 51Cr EDTA GFR rose significantly from baseline after the combination of indomethacin and misoprostol (from mean +/- SD 117 +/- 7.1 to 123 +/- 8.0 mls/min/1.73 m2, p = 0.05). When indomethacin alone was given 51Cr EDTA GFR did not change significantly (120 +/- 9.0 to 117 +/- 9.0 mls/min/1.73 m2). However in 4 of these subjects 51Cr EDTA GFR fell (range 7-19 mls/min/1.73 m2); in each of these the reduction was reversed when the indomethacin was given together with misoprostol. In the whole group the change in 51Cr EDTA GFR, from baseline, after indomethacin plus misoprostol was significantly different from that after indomethacin alone (+6 +/- 8 vs -3 +/- 5 mls/min/1.73 m2 p = 0.05). Misoprostol alone had no effect on GFR. We conclude that misoprostol and indomethacin in combination increase GFR in healthy volunteers, and further studies are now warranted to determine whether misoprostol is beneficial in the prophylaxis and treatment of NSAID-induced renal impairment.

Adult↗
PubMed1991

The pro-drug sulindac may reduce the risk of intestinal damage associated with the use of conventional non-steroidal anti-inflammatory drugs.

To test the hypothesis that administration of a non-steroidal anti-inflammatory drug formulated as a pro-drug, inactive as a cyclooxygenase inhibitor until after absorption, might cause less intestinal damage than conventional non-steroidal anti-inflammatory drugs, intestinal permeation to 51Cr-EDTA and mannitol was assessed in healthy volunteers before and after oral treatment for 1 week with either the pro-drug sulindac or the conventional non-steroidal anti-inflammatory drug indomethacin. Indomethacin, but not sulindac, significantly increased intestinal permeation to 51Cr-EDTA and reduced haemoglobin and haematocrit; neither affect mannitol permeation.

Adult↗
PubMed1991

Peripheral blood neutrophils in inflammatory bowel disease: morphological evidence of in vivo activation in active disease.

Morphological evidence of activation in vivo of circulating neutrophils in patients with inflammatory bowel disease (IBD) was sought by quantitative light microscope examination of toluidine blue-stained preparations made from peripheral venous bloods that had been fixed immediately ex vivo. The proportion of spherical (unactivated) circulating neutrophils was reduced in active Crohn's disease (73%; 46-96 (median; range), n = 11) compared with inactive Crohn's (90%; 45-99; n = 18, P less than 0.01) and normal subjects (94%; 44-98; n = 13, P less than 0.05). There tended to be fewer spherical neutrophils in active ulcerative colitis (77%; 13-96; n = 17) than in quiescent colitis (88%; 57-99, n = 13, P less than 0.1) or normal subjects (P less than 0.05). Activated neutrophils occur in the circulating pool of patients with active IBD and can be detected by light microscopy of peripheral venous blood leucocyte preparations.

Adult↗
PubMed1989

Pouchitis.

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Anal Canal↗
PubMed1989

Failure of allopurinol to modify urinary composition in enteric hyperoxaluria.

Conventional treatment of enteric hyperoxaluria (EHO) consists of dietary restriction of oxalate and fat and correction of its underlying cause whenever possible. Recent work suggests that allopurinol reduces the incidence of urolithiasis and the urinary excretion of both oxalate and uric acid in patients without intestinal disease. We have assessed the effect of allopurinol, 300 mg daily for 2 weeks, on urine biochemistry in patients with EHO due to small bowel Crohn's disease and/or resections. Compliance with treatment was confirmed by a fall in plasma uric acid in every patient. Allopurinol failed to alter 24 h urinary oxalate excretion or oxalate concentration. There were also no significant changes in the urinary excretion of glycollate (like oxalate, a breakdown product of glyoxylate), citrate, magnesium or calcium, each of which was at the lower end of the normal range before and during treatment with allopurinol. It appears unlikely that allopurinol will prove useful in the prevention of urolithiasis in patients with EHO.

Adult↗
PubMed1987

Is microscopic colitis due to bile-salt malabsorption?

The cause of the recently described syndrome of chronic watery diarrhea associated with microscopic colitis is unknown. A patient appearing to have this disorder is described here. A major pathophysiologic role for bile-salt malabsorption in her, and perhaps other such patients, was suggested by her clinicopathologic response to cholestyramine.

Adult↗