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Biomedical subjects

D S Rampton

Publications and source records attributed to D S Rampton.

At least 19 recordsLinked to original sources

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.

Clinical Trials as Topic↗

Molecular characterization of the bacteria adherent to human colorectal mucosa.

AIMS: To study large intestinal mucosal bacterial communities by Denaturing Gradient Gel Electrophoresis (DGGE) profiling and sequencing of 16S rRNA gene polymerase chain reaction (PCR) products amplified from DNA extracted from colorectal biopsies taken from healthy individuals. The specific aims were to determine how similar the mucosa-associated bacterial communities are within and between individuals and also to characterize the phylogenetic origin of isolated DGGE bands. METHODS AND RESULTS: Human colorectal biopsies were taken at routine colonoscopy from 33 patients with normal looking mucosa. The DNA was extracted directly from single biopsies and the bacterial 16S rDNA PCR amplified. The PCR products were profiled using DGGE to generate a fingerprint of the dominant members of the bacterial community associated with the biopsy. The reproducibility of this method was high (>98%). Washed and unwashed biopsies gave similar DGGE banding patterns (Median Similarity Coefficient - MSC 96%, InterQuartile Range - IQR 3.0%, n = 5). Adjacent biopsies sampled from the same patient using different forceps gave similar DGGE profiles (MSC 94%, n = 2). Two colorectal biopsies sampled at locations 2-5 cm apart, from each of 18 patients, resulted in very similar profiles (MSC 100%, IQR 2.8%). Biopsies sampled from different locations within the large intestine of the same patient also gave similar DGGE profiles (MSC 98% IQR 3.3%n = 6). Although all patients (n = 33) gave different DGGE profiles, some similarity (c. 34%) was observed between profiles obtained from 15 patients arbitrarily selected. 35 DGGE bands were excised and sequenced. Many were found to be most closely related to uncultured bacterial sequence entries in the Genbank database. Others belonged to typical gut bacterial genera including Bacteroides, Ruminococcus, Faecalibacterium and Clostridium. CONCLUSIONS: Bacterial communities adherent to colorectal mucosa within a normal patient show little variation; in contrast, mucosal bacterial communities sampled from different patients with normal colorectal mucosa show a high degree of variation. SIGNIFICANCE AND IMPACT OF THE STUDY: This research demonstrates that DGGE profiling of 16S rRNA gene PCR products amplified from DNA extracted directly from mucosal samples offers fresh insight into the bacterial communities that are adherent to colorectal mucosa. These findings are important with respect to further studies on the gastrointestinal tract in health and disease.

Adenomatous Polyposis Coli↗

Synchronous colectomy and caesarean section for fulminant ulcerative colitis: case report and review of the literature.

Ulcerative colitis (UC) affects women of all ages, with a peak incidence in the third and fourth decades, at the prime of their reproductive years [Baiocco PJ, Korelitz BI (1984) The influence of inflammatory bowel disease and its treatment on pregnancy and fetal outcome. J Clin Gastroenterol 6(3):211-216]. We describe a case of fulminating UC at 28 weeks' gestation treated by combined emergency subtotal colectomy and caesarean section with excellent foetal and maternal outcome. A treatment algorithm is suggested, and the literature surrounding inflammatory bowel disease in pregnancy is reviewed.

Adult↗

Efficacy and tolerability of oral iron therapy in inflammatory bowel disease: a prospective, comparative trial.

BACKGROUND: In patients with inflammatory bowel disease, oral iron is anecdotally reported to be less effective and less well tolerated than in those without inflammatory bowel disease, and to increase disease activity. AIM: To study prospectively the effects of oral iron in patients with and without inflammatory bowel disease. METHODS: Patients with ulcerative colitis, Crohn's disease and non-inflammatory bowel disease controls, all with iron deficiency anaemia, were assessed with symptom diaries, a quality of life questionnaire (Inflammatory Bowel Disease Questionnaire; inflammatory bowel disease patients only) and blood tests to measure iron repletion, disease activity and antioxidant capacity before and after starting 4 weeks of oral iron. In patients with ulcerative colitis, sigmoidoscopic scoring and rectal biopsies for reactive oxygen metabolite production were performed before and after iron therapy. RESULTS: All groups showed increases in haemoglobin and ferritin. Iron intolerance occurred in about a quarter of patients in each group. Two of 33 (6%) of inflammatory bowel disease patients had a relapse during treatment. Symptoms worsened in ulcerative colitis, but not in Crohn's disease or non-inflammatory bowel disease patients; Inflammatory Bowel Disease Questionnaire scores improved in ulcerative colitis. Laboratory markers of disease activity, sigmoidoscopic scores, histological scores, antioxidant capacity levels and reactive oxygen metabolite production did not change. CONCLUSIONS: Oral iron is equally efficacious and well tolerated in inflammatory bowel disease and non-inflammatory bowel disease patients. A tiny minority of inflammatory bowel disease patients relapse in association with use of oral iron therapy.

Administration, Oral↗

Psychological stress in IBD: new insights into pathogenic and therapeutic implications.

Psychological stress has long been reported anecdotally to increase disease activity in inflammatory bowel disease (IBD), and recent well designed studies have confirmed that adverse life events, chronic stress, and depression increase the likelihood of relapse in patients with quiescent IBD. This evidence is increasingly supported by studies of experimental stress in animal models of colitis. With the evolving concept of psychoneuroimmunology, the mechanisms by which the nervous system can affect immune function at both systemic and gut mucosal levels are gradually becoming apparent. Recent data suggest that stress induced alterations in gastrointestinal inflammation may be mediated through changes in hypothalamic-pituitary-adrenal (HPA) axis function and alterations in bacterial-mucosal interactions, and via mucosal mast cells and mediators such as corticotrophin releasing factor (CRF). To date, the therapeutic opportunities offered by stress reduction therapy remain largely unexplored, in part because of methodological difficulties of such studies. This paper reviews recent advances in our understanding of the pathogenic role of psychological stress in IBD and emphasises the need for controlled studies of the therapeutic potential of stress reduction.

Acute Disease↗

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 </= 2), sigmoidoscopic remission (Baron score </= 1) and histological remission (Saverymuttu score </= 1). Secondary outcome measures included changes in the Simple Clinical Colitis Activity Index (improvement was defined as a decrease of >/= 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.

Administration, Oral↗

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.

Adult↗

Evaluation of new therapies for inflammatory bowel disease.

The pathophysiology of inflammatory bowel disease (IBD) is gradually being unravelled and new therapies are being developed to target the disturbed biological processes. This article outlines the clinical features of IBD, its current therapy and pathogenesis. The difficulties for clinical pharmacologists and gastroenterologists associated with designing, executing and interpreting clinical trials in IBD are then discussed. The final section reviews methods that can used to demonstrate the pharmacological actions of new treatments in patients with IBD. It is emphasized that proof of the therapeutic efficacy of a novel agent with a specific mechanism of action yields not only clinical benefit to patients with IBD, but also indicates the importance of the targeted biochemical pathway in the pathogenesis of the disease.

Biopsy↗

Expression of heat shock protein 32 (hemoxygenase-1) in the normal and inflamed human stomach and colon: an immunohistochemical study.

Heat shock protein 32 (Hsp32, hemoxygenase-1) is induced by reactive oxygen metabolites (ROM) and degrades heme leading to the formation of antioxidant bilirubin. Increased mucosal generation of ROM occurs in gastritis and inflammatory bowel disease. We aimed to assess mucosal expression of Hsp32 in normal stomach and colon and to test the hypothesis that disease-related differential expression occurs in inflamed tissue. Gastric body and antral mucosal biopsies were obtained from 33 patients comprising Helicobacter pylori-negative normal controls (n = 8), H pylori-negative gastritis patients (n = 11), and H pylori-positive gastritis patients (n = 14). Forty-seven archival colonic mucosal biopsies selected comprised normal histology (n = 10), active ulcerative colitis (UC) (n = 9), inactive UC (n = 8), active Crohn's disease (CD) (n = 8), inactive CD (n = 6), and other colitides (n = 6). Hsp32 expression in formalin-fixed sections was assessed by avidin-biotin peroxidase immunohistochemistry using a polyclonal rabbit anti-Hsp32 as the primary antibody. Immunohistochemical staining identified Hsp32 in all groups. Diffuse cytoplasmic staining was seen in gastric and colonic epithelial and lamina proprial inflammatory cells. Staining scores for Hsp32 were higher in antral H pylori-positive (P = 0.002) and H pylori-negative (P = 0.02) gastritis than in controls and in body H pylori-positive gastritis than in the other 2 groups (P < 0.01). Expression of Hsp32 was increased in active UC compared with inactive disease (P = 0.03) and normal controls (P = 0.02). In conclusion, Hsp32 is expressed constitutively in normal gastric and colonic mucosa, and differential expression occurs in these tissues when they are inflamed. Upregulation of Hsp32 may be an adaptive response to protect mucosa from oxidative injury in patients with gastritis and inflammatory bowel disease.

Colitis, Ulcerative↗

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.

Adult↗

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.

Adolescent↗

Thromboxane synthase immunohistochemistry in inflammatory bowel disease.

BACKGROUND: Thromboxanes are produced in excess in inflammatory bowel disease. Preliminary reports suggest that ridogrel, a thromboxane synthase inhibitor, is anti-inflammatory and may have therapeutic benefits in patients with ulcerative colitis. AIMS: To investigate the immunohistochemical expression of thromboxane synthase in the colorectal mucosa of patients with inflammatory bowel disease. METHODS: Immunostaining of colonic biopsies from patients with inflammatory bowel disease (n = 13) and controls (n = 5) was performed using a monoclonal antibody to human thromboxane synthase. The extent of staining in cells of the lamina propria was compared in patient and control groups, and was assessed in relation to disease activity scored macroscopically and histologically. RESULTS: The percentage of cells in the lamina propria staining for thromboxane synthase was higher in patients with active inflammatory bowel disease than in those with inactive disease or in controls (p = 0.02 and p = 0.002, respectively). There was a direct correlation between disease activity, measured endoscopically and histologically, and the percentage of lamina propria cells staining for thromboxane synthase (R = 0.71, p = 0.001 and R = 0.72, p = 0.001, respectively). CONCLUSIONS: Increased thromboxane synthase expression in lamina propria cells occurs in active inflammatory bowel disease. It is possible that this results in increased thromboxane synthesis, which may in turn contribute to mucosal inflammation and intramucosal thrombogenesis.

Adult↗

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.

Complementary Therapies↗