Publications by authors named "Duncombe V"

Culture-independent molecular techniques have demonstrated that the majority of the gut microbiota is uncultivable. Application of these molecular techniques to more accurately identify the indigenous gut microbiome has moved with great pace over recent years, leading to a substantial increase in understanding of gut microbial communities in both health and a number of disorders, including irritable bowel syndrome (IBS). Use of culture-independent molecular techniques already employed to characterise faecal and, to a lesser extent, colonic mucosal microbial populations in IBS, without reliance on insensitive, traditional microbiological culture techniques, has the potential to more accurately determine microbial composition in the small intestine of patients with this disorder, at least that occurring proximally and within reach of sampling.

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Objective: The aim of this study was to investigate the separate effects of indigenous oropharyngeal- and colonic-type flora on small intestinal mucosal immunity and morphometry in small intestinal bacterial overgrowth (SIBO).

Methods: A duodenal aspirate and random biopsies of underlying mucosa were obtained from 52 adult subjects (age range, 18-90 yr; median, 60 yr) without disorders that may otherwise disturb small intestinal histology or mucosal immunity. Villus height, crypt depth, villus/crypt ratios, counts of intraepithelial lymphocytes (IELs) and lamina propria total mononuclear cells, IgA, IgM, and IgG plasma cells, mast cells, and B and T lymphocytes were determined in relation to the presence or absence of SIBO and the nature of the overgrowth flora in all subjects.

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Objectives: The aims of this study were 1) to document the sensitivity, specificity, and predictive values of the rice breath hydrogen test for small intestinal bacterial overgrowth; 2) to determine the possible influence of concurrent gastric bacterial overgrowth and gastroduodenal pH on the efficacy of this test; and 3) to investigate whether reliability is limited by an inability of small intestinal luminal flora to ferment rice or its product of hydrolysis, maltose.

Methods: Twenty adult subjects were investigated with microbiological culture of proximal small intestinal aspirate and a 3-g/kg rice breath hydrogen test. Gastroduodenal pH, the presence or absence of gastric bacterial overgrowth, and the in vitro capability of small intestinal luminal flora to ferment rice and maltose, its product of hydrolysis, were determined.

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Murine studies have demonstrated that the presence of indigenous gut flora is crucial for the induction of systemic immune hyporesponsiveness to antigens initially encountered within the gastrointestinal lumen. This study investigated whether increased titers of such flora, as occur in human small intestinal bacterial overgrowth, may be associated with increased suppression of systemic immune responsiveness and the possible relation between systemic and mucosal immunity in this setting. Serum total immunoglobulin (Ig), immunoglobulin subclass, and soluble interleukin-2 receptor levels and lamina propria IgA plasma cell counts were determined in 50 consecutive subjects with (N = 30) and without (N = 20) small intestinal bacterial overgrowth.

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Our aim was to determine the relationships between interleukin-6 and immunoglobulin levels within small intestinal luminal secretions. Twenty adult subjects with small intestinal bacterial overgrowth (N = 13), irritable bowel syndrome (N = 4), and nonulcer dyspepsia (N = 3) underwent endoscopic aspiration of secretions from the small intestinal mucosal surface for assessment of IL-6, IgA1, IgA2, IgM, IgG1, IgG2, IgG3, and IgG4 concentrations. Serum immunoglobulin concentrations and small intestinal histology were also determined.

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Objective: Elevated antigliadin antibody levels in small intestinal luminal secretions of subjects with normal or only mildly abnormal small intestinal histology are considered indicative of "latent" or "potential" celiac disease. The purpose of this study was to determine whether small intestinal bacterial overgrowth (SIBO) might provide an alternative explanation for positive luminal antigliadin antibodies in such subjects.

Methods: Twenty-six adult subjects without predisposition to disturbed mucosal immunity were investigated with culture of small intestinal luminal secretions.

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It is unknown whether bacteriolysis due to luminal complement activation contributes to local defense mechanisms against small intestinal bacterial overgrowth, particularly with gram-negative bacteria. This study addressed this issue. Thirty adult subjects were investigated with culture of luminal secretions adherent to proximal small intestinal mucosa.

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Background: The influence of luminal bacteria on small-intestinal permeability has not been fully assessed. This study addressed this issue.

Methods: Thirty-four subjects (mean age 64 years; range 22-95 years) were investigated for possible small-intestinal bacterial overgrowth (SIBO) with culture of a small-intestinal aspirate.

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Objective: 1) To determine the prevalence of small intestinal overgrowth with colonic-type bacteria in symptomatic elderly subjects, particularly those without important "clues" such as clinically apparent predisposition or vitamin B12 deficiency, and 2) to investigate defense mechanisms such as gastric acidity, small intestinal motility, and luminal IgA in this setting.

Methods: Fifty-two symptomatic subjects without vitamin B12 deficiency or clinically apparent predisposition to bacterial overgrowth or disturbed mucosal immunity, including 22 subjects > or = 75 yr old, underwent culture of small intestinal luminal secretions. Indicator paper was used to measure fasting gastric pH.

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Background: The independent influences of small-intestinal bacterial overgrowth and old age on mucosal immunoglobulin production and secretion have not been assessed. This is an important issue, since luminal IgA deficiency may exacerbate small-intestinal bacterial overgrowth, the prevalence of which is high in selected elderly populations.

Methods: Proximal small-intestinal aspirates were obtained from 33 subjects for bacteriologic analysis and measurement of total IgA, IgM, total IgG.

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Background: Factors regulating proximal small-intestinal luminal concentrations of IgG3, the predominant IgG subclass at this site, are unclear. This study determined whether luminal IgG3 concentrations are related to those of complement protein 4 (C4), an acute-phase reactant predominantly derived from local mucosa.

Methods: Proximal small-intestinal luminal and peripheral blood IgG subclass and C4 concentrations were measured by radial immunodiffusion in 30 adult subjects without predisposition to disturbed mucosal immunity.

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Objective: Small intestinal hypomotility is an important cause of small intestinal bacterial overgrowth, yet assessment of small intestinal motility in this setting is problematic. This study was performed to investigate the validity of a bacteriological method for detecting small intestinal hypomotility.

Methods: Twenty-five subjects without previous gastric surgery were studied with (i) concurrent bacteriological analyses of fasting saliva and gastric and proximal small intestinal aspirates, (ii) measurement of gastric pH, and (iii) scintigraphic assessment of small intestinal transit rates of a liquid test meal.

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Background: Mucosal production of interferon-gamma, interleukin-6, and tumour necrosis factor-alpha is increased in inflammatory bowel disease and parallels disease activity. Interferon-gamma production is also increased in coeliac disease. Conversely, local cytokine profiles have not been investigated in small-intestinal bacterial overgrowth.

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Objectives: To i) document the sensitivity and specificity of a combined scintigraphic/lactulose breath hydrogen test for small intestinal bacterial overgrowth and ii) investigate the validity of currently accepted definitions of an abnormal lactulose breath hydrogen test based on "double peaks" in breath hydrogen concentrations.

Methods: Twenty-eight subjects were investigated with culture of proximal small intestinal aspirate and a 10-g lactulose breath hydrogen test combined with scintigraphy. Gastroduodenal pH, the presence or absence of gastric bacterial overgrowth, and the in vitro capability of overgrowth flora to ferment lactulose were determined.

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Two patients with scleroderma (systemic sclerosis, SSc) and chronic blood loss secondary to gastric vascular ectasia--"watermelon stomach"--are presented. These cases exemplify the condition of gastric vascular ectasia and highlight the increasingly recognized association with autoimmune antibodies and connective tissue disease such as SSc. In both cases the onset of gastric blood loss coincided with the clinical manifestations of sclerodactyly by months, suggesting some temporal relationship.

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Rice carbohydrate malabsorption is common in Burmese village children and adults and may contribute to diminished growth. Its diagnosis depends on a rice breath hydrogen test, which has limitations. Almost 20% of Burmese children under age 5 produce methane, compared with less than 7% of children in Africa and Hong Kong.

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While up to 50% of Western populations produce methane, this is less than that of rural black Africans and there is no information on methane production in populations from Asian developing countries. Females consistently produce methane more commonly than males, and methane production in children under the age of five years, except in Nigeria, is unusual. Breath methane was sampled in 1426 subjects from Myanmar ranging in age from 1 month to 88 years, with a mean age of 26.

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Objectives: To document the sensitivity of the 1-g 14C-D-xylose breath test for bacterial overgrowth and to investigate luminal and nonluminal factors that may influence breath 14CO2 levels and impact on the clinical utility of this test.

Methods: Thirty-five adult subjects were investigated for bacterial overgrowth by culture of gastric and small intestinal aspirates and by a 1-g 14C-D-xylose breath test. Body weight, gastroduodenal pH and the in vitro capability of overgrowth flora to ferment D-xylose were assessed.

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Background: Although culture of luminal secretions is regarded as the most accurate diagnostic test for small-intestinal bacterial overgrowth, obtaining an aspirate is often difficult owing to the sparseness of luminal secretions present at the time of aspiration. Obtaining a mucosal biopsy specimen for bacteriologic analysis would overcome this problem.

Methods: Culture of small-intestinal and gastric aspirates and unwashed small-intestinal mucosal specimens was performed in 51 adult subjects investigated for small-intestinal overgrowth.

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The efficacy of a string test for the detection of small bowel bacterial overgrowth (SBBO) was determined by comparison with a sterile endoscopic method for sampling small bowel secretions in 15 subjects investigated for SBBO. Clinical value was found to be limited by poor sensitivity, specificity and positive predictive value. The string test is not an adequate substitute for oro-duodenal intubation for the detection of SBBO.

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Background: Although elevated fasting breath hydrogen concentrations have been reported in small-intestinal bacterial overgrowth, this diagnosis has been presumptive or based on definitions that vary from study to study. The influence of gastric bacterial overgrowth and gastroduodenal pH has not been documented. Conflicting evidence exists as to the reproducibility of breath hydrogen measurements.

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Breath hydrogen tests were performed after a rice meal (3 g of cooked rice/kg of body weight, equivalent to 1 g of carbohydrate/kg of body weight) on 256 village children (age range 1-59 months) who were known hydrogen (H2) producers. Anthropometric measurements were made every three months and growth rates were calculated. A breath H2 excretion pattern that suggested small bowel bacterial overgrowth (SBBO), which was recognized as a transient maximum level of 10 ppm or more at 20-, 40-, or 60-min breath samples following the rice meal, was present in 53 (20.

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Lactulose breath hydrogen test and Enterotest string test were carried out simultaneously on 19 children 3-5 years old. Bacteria isolated from the jejunal fluid in upper small intestines of these children were incubated with lactulose at neutral pH. Anaerobes were present in all but one child, and in 15 children they were present in numbers greater than 5 log10 organisms per ml.

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