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D S Rampton

Publications and source records attributed to D S Rampton.

At least 55 records · Page 3Linked to original sources
PubMed1998

Community-acquired Clostridium difficile-associated diarrhoea in a patient with colonic carcinoma.

In the vast majority of cases, Clostridium difficile-associated diarrhoea and pseudomembranous colitis develop following the use of antibiotics. We report a case in which C. difficile-associated diarrhoea was diagnosed in the absence of previously reported predisposing factors. It transpired that the patient had a colonic carcinoma. We suggest that a diagnosis of C. difficile-associated diarrhoea in the absence of a history of antibiotics or other established causes should prompt a colonoscopy to search for alternative explanations for the alteration in bowel flora which such an infection indicates.

Aged↗
PubMed1997

Review article: platelets in inflammatory bowel disease--pathogenetic role and therapeutic implications.

An elevated platelet count is well recognized as a marker of inflammatory bowel disease activity. There is an increased incidence of systemic thromboembolism in this disease. Recent work indicates that platelets exhibit several proinflammatory properties including release of inflammatory mediators, and recruitment, chemotaxis and modulation of the activity of other inflammatory cells. Furthermore there is evidence that microvascular thrombosis and a procoagulant state may play a role in the pathogenesis of inflammatory bowel disease. These observations prompted recent studies of platelet activity in inflammatory bowel disease, which indicate enhanced platelet aggregation in vivo and in vitro, and increased platelet activation as measured by increased release of intracellular proteins into plasma and expression of platelet surface markers, including P-selectin and GP53. These abnormalities could contribute to the pathogenesis of inflammatory bowel disease by enhancing inflammation and promoting microinfarction. Aminosalicylates reduce platelet activity although they also have many other additional properties to explain their efficacy in inflammatory bowel disease. There are however several specific antiplatelet drugs now available which may provide new therapeutic possibilities in the management of this disease.

Animals↗
PubMed1997

Eicosanoids: role in gastrointestinal inflammation and cancer.

This paper contains a brief review of the metabolism and physiological actions of eicosanoids, with a discussion of the potential clinical implications of disturbances in eicosanoid metabolism, particularly in NSAID-induced upper gastrointestinal damage and inflammatory bowel disease. There follows a summary of current evidence for the role of eicosanoids in the pathogenesis of colorectal neoplasia.

Animals↗
PubMed1997

Platelet aggregation and neutrophil sequestration in the mesenteric circulation in inflammatory bowel disease.

BACKGROUND AND OBJECTIVES: Mesenteric microvascular thrombosis may be an early pathogenic event in Crohn's disease (CD), and intravascular platelet aggregates have been identified in mucosal biopsies in ulcerative colitis (UC). Activated platelets are involved in thrombogenesis and exhibit inflammatory properties. In active inflammatory bowel disease (IBD) increased numbers of platelet aggregates are detectable in the peripheral circulation. The aim of this study was to test the hypothesis that in IBD, platelet aggregation is triggered in the mesenteric vasculature. PATIENTS AND METHODS: Platelet numbers, platelet aggregate ratios and differential leucocyte counts were compared in mesenteric arterial and venous blood obtained from paired vessels at the time of intestinal resection from 13 patients with inflammatory bowel disease and, as controls, 6 patients with colonic carcinoma or diverticular disease. RESULTS: In UC and CD, but not in controls, fewer neutrophils were found in blood draining the intestine compared with that supplying it (arteriovenous gradient median 1.0 x 10(9)/l (interquartile range 0.2-1.3) for UC, P < 0.05; 0.8 (0.2-1.5) for CD, P < 0.02; 0.4 (-0.3-1.1) for controls, P = NS). In CD, increased numbers of circulating platelet aggregates were identified in venous samples (platelet aggregate ratio 0.83 (0.71-0.93)) than in paired arterial samples (0.99 (0.95-1.01), P < 0.02) and control venous samples (0.99 (0.93-0.97), P < 0.05). The mesenteric arteriovenous gradient for neutrophils in IBD reflects their migration into the extravascular tissue and lumen of the inflamed intestine. Increased circulating platelet aggregates in the mesenteric venous circulation support the hypothesis that platelet activity is stimulated in the mesenteric microcirculation in CD.

Adult↗
PubMed1996

Epidemiology of inflammatory bowel disease in different ethnic and religious groups: limitations and aetiological clues.

We present a review of epidemiological studies of inflammatory bowel disease and abdominal tuberculosis in various migrant communities in the United Kingdom. The differences between various South Asian groups such as Gujaratis, Bangladeshis and Punjabis are discussed in the context of age standardisation of incidence data and various dietary and social activities.

Asia↗
PubMed1996

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147-325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61-140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64-206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.

Adult↗
PubMed1996

Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis.

BACKGROUND: Reactive oxygen species may mediate tissue injury in inflammatory bowel disease. Aminosalicylates have antioxidant activity and the antioxidants, superoxide dismutase and allopurinol, are of reported benefit in inflammatory bowel disease. AIM: To develop a convenient technique for testing the antioxidant potential of standard and novel therapeutic agents for use in inflammatory bowel disease. METHODS: Amplified chemiluminescence was used to measure reactive oxygen species production by colonic biopsy specimens from rats with acetic acid induced colitis and to assess the in vitro effect of conventional antioxidants, standard therapies and proposed novel therapies for inflammatory bowel disease. RESULTS: The model was validated by demonstrating that the profile of effects on chemiluminescence of acetic acid induced colitis biopsy specimens given by conventional antioxidants (sodium azide, catalase, copper-zinc superoxide dismutase, dimethyl sulphoxide, N-acetylcysteine and ascorbate) and standard therapies (5-aminosalicylate and hydrocortisone) resembled that previously reported using biopsy specimens from ulcerative colitis. Human recombinant manganese superoxide dismutase did not alter chemiluminescence. Two novel compounds, LY231617 (10 mM) and amflutizole (20 mM), reduced chemiluminescence by 98% (n = 5, p = 0.009) and 88% (n = 5, p = 0.03), respectively. CONCLUSIONS: The similarity of the chemiluminescence responses of colonic biopsy specimens from acetic acid induced colitis and ulcerative colitis to a range of conventional antioxidants and standard treatments suggests that this model is a useful method for testing the antioxidant potential of new therapies for inflammatory bowel disease. The antioxidant actions of dimethyl sulphoxide, ascorbate, and the novel compounds, amflutizole and LY231617 in this model suggest that these agents merit further assessment in the treatment of inflammatory bowel disease.

Acetic Acid↗
PubMed1995

Increased expression of cell adhesion molecule P-selectin in active inflammatory bowel disease.

The pathogenic changes of inflammatory bowel disease (IBD) depend on migration of circulating leucocytes into intestinal tissues. Although leucocyte rolling and tenuous adhesion are probably regulated by inducible selectins on vascular endothelia, little is known about the expression of these molecules in Crohn's disease and ulcerative colitis. Using immunohistochemistry on surgically resected specimens, this study investigated endothelial P-selectin (CD62, granular membrane protein-140) in frozen sections of histologically uninvolved tissues adjacent to inflammation (Crohn's disease = 10; ulcerative colitis = 10), from highly inflamed areas (Crohn's disease = 20; ulcerative colitis = 13), and from normal bowel (n = 20). By light microscopy, two forms of P-selectin immunoreactivity were detected that apparently corresponded ultrastructurally to stored and released distributions. Compared with the normal gut, there was a 3.7-fold increase of P-selectin immunoreactivity on veins (p < 0.0001), venules (p < 0.0001), and capillaries (p < 0.05) in the highly inflamed gut, without differences between Crohn's disease and ulcerative colitis. In the uninvolved gut, P-selectin expression was similar to that seen in normal controls, except for a focal increase of P-selectin in the vicinity of small lymphocyte aggregates. The dramatic upregulation of P-selectin in the inflamed tissue and its potential role in leucocyte trafficking support the concept of P-selectin blocking therapy for the control of active IBD.

Adolescent↗
PubMed1995

Diagnostic and therapeutic push type enteroscopy in clinical use.

This study describes small bowel push enteroscopy in routine clinical practice, using a purpose designed instrument (Olympus SIF-10). Fifty six patients had a total of 60 procedures over a two and a half year period. The median (range) depth of small intestine intubated was 45 (15-90) cm. Procedure time varied from 10-45 minutes. Most enteroscopies were performed during routine gastroscopy lists. The technique was comparatively easy for experienced endoscopists to learn. Forty two procedures were for diagnostic purposes. Eleven patients had gastrointestinal bleeding where the source was obscure, or where early investigations had suggested a small bowel source: a specific diagnosis was made in 45% of these cases. Of seven iron deficient anaemic patients using non-steroidal anti-inflammatory drugs (NSAIDs), only one had a lesion detected in the upper small bowel. Nine patients had abnormal small bowel barium studies. Small bowel abnormalities were seen in six cases and were definitively diagnostic in three of these; in three patients the barium study appearances were confirmed as artefact. Fifteen patients were investigated for abdominal symptoms suggesting small bowel obstruction or malabsorption: a diagnosis was made in five cases. Fifteen patients underwent enteroscopy for therapeutic purposes, including successful treatment of difficult enteral feeding problems by nasojejunal tubes or by cutaneous endoscopic jejunostomies, polypectomy for Peutz-Jeghers syndrome, and dilatation of strictures. Additionally, bleeding lesions detected in patients during investigation of anaemia were successfully treated at the time by YAG laser or bipolar diathermy. In conclusion, push enteroscopy is a practical and valuable clinical service, which should probably become available on a subregional basis.

Adolescent↗
PubMed1994

Platelets circulate in an activated state in inflammatory bowel disease.

BACKGROUND/AIMS: Platelets show proinflammatory as well as prothrombotic properties. Patients with inflammatory bowel disease are at increased risk of systemic thromboembolism, and multifocal microvascular infarction has been proposed as a pathogenetic mechanism in Crohn's disease. The aim of this study was to determine if inflammatory bowel disease is associated with abnormal platelet behavior. METHODS: Platelet activation and aggregability were assessed using flow cytometry, Born aggregometry, and the modified method of Wu and Hoak. Serum beta-thromboglobulin was measured in patients with Crohn's disease and ulcerative colitis and, as controls, in healthy volunteers and patients with active rheumatoid arthritis. RESULTS: Platelet surface expression of P-selectin and GP53 (markers of activation) were increased in Crohn's disease (13 of 30 patients abnormal for P-selectin; 9 of 28 abnormal for GP53) (P < 0.01) and ulcerative colitis (9 of 21 for P-selectin; 10 of 21 for GP53) (P < 0.01) compared with healthy controls. Increased circulating platelet aggregates (15 of 24 patients with Crohn's disease and 8 of 16 with ulcerative colitis) (P < 0.01), platelet aggregability in vitro, and serum beta-thromboglobulin were detected in active inflammatory bowel disease compared with healthy controls. Platelet behavior in active rheumatoid arthritis resembled that in healthy controls. CONCLUSIONS: Increased platelet activation and aggregation are features of inflammatory bowel disease and may contribute to the risk of systemic thromboembolism and the pathogenesis of mucosal inflammation. Therefore, antiplatelet agents may be valuable in the management of inflammatory bowel disease.

Adult↗
PubMed1994

Increased leukotriene B4 release from ileal pouch mucosa in ulcerative colitis compared with familial adenomatous polyposis.

Pouchitis may complicate the construction of an ileal pouch after colectomy for ulcerative colitis (UC) but not familial adenomatous polyposis (FAP). To examine whether differences in eicosanoid metabolism might explain why pouchitis is largely confined to UC patients, this study compared arachidonic acid stimulated release of immunoreactive leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) from macroscopically uninflamed pouch mucosal biopsy specimens incubated in vitro from patients with UC and FAP. The study also compared eicosanoid release from inflamed and uninflamed pouches in patients with UC. In uninflamed pouches, median LTB4 release was nearly twice as high in UC as in FAP (p = 0.001), but there was no significant difference in PGE2 production. In UC, stimulated eicosanoid release from uninflamed functioning pouch mucosa was not significantly different from that from either ileostomy or defunctioned pouch mucosa. LTB4 and PGE2 release were significantly greater from inflamed than uninflamed pouch mucosa in UC (p = 0.001 and 0.01, respectively). Leukotriene synthesis inhibition or receptor antagonism, or both merit therapeutic evaluation in pouchitis. Increased release of LTB4 from endoscopically normal pouch mucosa suggests increased 5-lipoxygenase activity in patients with UC and could contribute to their predisposition to pouchitis.

Adenomatous Polyposis Coli↗
PubMed1994

High prevalence of Helicobacter pylori metronidazole resistance in migrants to east London: relation with previous nitroimidazole exposure and gastroduodenal disease.

A high prevalence of metronidazole resistance in Helicobacter pylori is reported in developing countries. This study examined whether migrants referred for diagnostic gastroscopy at a United Kingdom centre (n = 54), had a higher prevalence of metronidazole resistance than subjects born in the United Kingdom attending endoscopy (n = 46). Records of nitroimidazole treatment prescribed in the United Kingdom was obtained in 83 patients to find out if there was an association between H pylori metronidazole resistance and previous ingestion of either metronidazole or tinidazole. The prevalence of metronidazole resistant isolates varied according to country of birth: Bangladesh (90%, 27 of 30), other countries (67%, 16 of 24), and United Kingdom (37%, 17 of 46) (p < 0.001). Among those born in the United Kingdom, women were more likely to harbour resistant H pylori than men (54% v 18% respectively, p = 0.01) and more likely to have a history of previous nitroimidazole ingestion (41% v 11% respectively, p = 0.02). Patients previously exposed to either metronidazole or tinidazole were more likely to harbour resistant strains (84% (27 of 32) v 41% (21 or 51), p < 0.0001). The distribution of gastroduodenal disease, assessed endoscopically, was not affected by metronidazole resistance status.

Adult↗
PubMed1994

Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite production in vivo.

To determine if reactive oxygen metabolites have a pathogenic role in Helicobacter pylori (H pylori) related gastroduodenal disease, this study measured their production in antral mucosal biopsy specimens. Two related chemiluminescence techniques were used comparing H pylori positive (n = 105) and negative patients (n = 64) with a similar spectrum of macroscopic disease. After chemiluminescence assays, biopsy specimens were graded histologically. Increased luminol dependent chemiluminescence (detecting reactive oxygen metabolites through peroxidase catalysed reactions) was found in H pylori positive patients (median photon emission = 6.4 x 10(3)/min/mg wet weight (95% confidence intervals 3.6 to 9.9)) but not H pylori negative cases (-0.9 (-1.3 to -0.6)) (p = 0.0001). Similar results were found using lucigenin (which reacts directly with oxygen metabolites, particularly superoxide): (H pylori positive 0.9 (0.1 to 3.2); H pylori negative -1.2 (-3.4 to -0.6)) (p = 0.0003). Chemiluminescence was greater in H pylori positive compared with negative tissue when samples were grouped by equivalent macroscopic or microscopic damage. This difference was in part accounted for by a greater neutrophil infiltration in the H pylori positive mucosa, but when biopsy specimens with equivalent neutrophil infiltration could be compared directly, positive specimens gave greater chemiluminescence than negative. Smoking, drugs, and alcohol consumption had no independent effect. It is concluded that excess mucosal reactive oxygen metabolite production is associated with H pylori gastric antral infection and may be an important pathogenic mechanism. There is no evidence for reactive oxygen metabolite participation in the pathogenesis of gastric mucosal injury in cases unrelated to H pylori infection.

Antioxidants↗
PubMed1994

Technetium-99m hexamethylpropyleneamineoxime labelled leucocyte scanning in the initial diagnosis of Crohn's disease.

The technetium hexamethylpropyleneamineoxime labelled white cell scan (WCS) is not widely used as a screening test for Crohn's disease primarily because, though sensitive, it is perceived as being insufficiently specific. A series of 42 patients screened for Crohn's disease by this method was analysed retrospectively. The sensitivity was 100% and specificity 91%. This performance was maintained in a subgroup of these patients with very low prevalence of disease. If appropriate criteria for interpretation are used the WCS is a specific as well as a sensitive screening test for Crohn's disease.

Adolescent↗
PubMed1994

Relationship between infective load of Helicobacter pylori and reactive oxygen metabolite production in antral mucosa.

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'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.

Adolescent↗