How can we reduce the incidence and mortality of colorectal cancer?
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Australia↗
Biomedical subjects
T D Bolin
Publications and source records attributed to T D Bolin.
Local and systemic complement activity in small intestinal bacterial overgrowth.
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. Luminal and plasma concentrations of C3 and C3d and C3d/C3 ratios were determined. Activated terminal complement complex was sought in surface epithelium to which aspirated secretions had been adherent. Small intestinal bacterial overgrowth with gram-negative bacteria was present in 12/30 (40.0%) subjects. C3, C3d, and C3d/C3 profile indicated that increased local but not systemic C3 activation occurs in this group. Conversely, no activation of terminal complement complex was evident in this circumstance. Thus, complement-mediated bacteriolysis is unlike to contribute to local defense mechanisms against small intestinal bacterial overgrowth, even when overgrowth flora includes gram-negative bacteria. Factors preventing full local activation of the complement cascade in this circumstance require investigation.
Adult↗
Sucralfate as an alternative to bismuth in quadruple therapy for Helicobacter pylori eradication.
BACKGROUND: There are persuasive arguments for treating all patients with Helicobacter pylori-associated peptic ulcer disease. However, the choice of therapeutic regimen remains problematical. Bismuth triple therapy produces greater than 80% cure of H. pylori infection, whereas omeprazole and bismuth quadruple therapy has produced cure rates in excess of 90%. Colloidal bismuth is not available in many countries, hence limiting the use of bismuth-based therapeutic regimens. We substituted widely available sucralfate for bismuth in a quadruple-therapy regimen. METHOD: We studied 223 consecutive patients with gastritis or peptic ulcer disease in whom H. pyori infection was confirmed by CLOtest (Delta West Ltd., Bentley, WA, Australia) or histological assessment. Successful therapy was validated by the 14C urea breath test 4 to 6 weeks after therapy. Omeprazole, 20 mg was given twice daily for 10 days. After 3 days of omeprazole sucralfate (1 gm qid), tetracycline (500 mg qid) and metronidazole (400 mg tid) were added for 7 days. RESULTS: Therapy was successful in 194 of 223 patients (87%). Compliance was excellent, with only two patients being unable to tolerate therapy. Side effects were minimal and included nausea, vomiting, headache, and vaginal moniliasis. At 6 months' follow-up, 10 of 210 patients (5%) who were previously documented as "cured" had a positive breath test. CONCLUSIONS: The wide availability of sucralfate in many countries makes it a possible alternative to bismuth for use in proton pump quadruple-therapy regimens, achieving a reasonable cure rate for H. pylori infection.
Adult↗
Luminal bacteria and small-intestinal permeability.
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. A lactulose/mannitol small-intestinal permeability test was performed, small-intestinal histology assessed and serum vitamin B12 concentrations measured in all subjects. Permeability was also assessed in a control group of 34 asymptomatic volunteers. RESULTS: Urinary lactulose/mannitol ratios were significantly increased in subjects with SIBO with colonic-type flora (P < 0.0005), even in the absence of villous atrophy. Urinary lactulose/mannitol ratios were increased in this group due to significantly increased urinary lactulose concentrations (P < 0.0005) rather than reduced urinary mannitol levels, after correcting for inter-subject variations in renal function. Counts of intraepithelial lymphocytes of CD8 phenotype were significantly increased in this group (P = 0.003). Although a significant correlation was found between intraepithelial lymphocyte counts and small-intestinal permeability overall (P < 0.002), these counts were not significantly different in subjects with SIBO with colonic-type flora whose permeability values were < or = > 0.028, the upper limit of normal in asymptomatic controls. Serum vitamin B12 concentrations did not differ significantly between groups (P > 0.5). Ageing did not independently influence small-intestinal permeability (P > 0.5). CONCLUSIONS: Small-intestinal permeability is increased in subjects with SIBO with colonic-type bacteria. This effect is independent of ageing and not mediated by vitamin B12 deficiency. Although counts of intraepithelial lymphocytes of CD8 phenotype are increased in this disorder, it is also unlikely that these cells play an important causative role in this process. Routine light microscopic assessment underestimates the prevalence of small-intestinal functional disturbance in this disorder.
Bacterial Infections↗
Small intestinal bacterial overgrowth in the symptomatic elderly.
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. The presence of bacteria of confirmed nonsalivary origin in small intestinal secretions served as an index of small intestinal dysmotility. Small intestinal luminal IgA concentrations were measured by radial immunodiffusion. RESULTS: Small intestinal overgrowth with colonic-type flora was not present in any subject investigated for dyspepsia, irrespective of age. In subjects with chronic diarrhea, anorexia, or nausea, overgrowth with colonic-type flora (Enterobacteriaceae) was present in 0/12 (0%), 1/10 (10.0%), and 9/14 (64.3%) subjects aged < 50 yr, 50-74 yr, and > or = 75 yr, respectively. Enterobacteriaceae were not concurrently recovered from saliva of any subject > or = 75 yr old with small intestinal overgrowth with these bacteria. Fasting hypochlorhydria was present in only 1/9 (11.1%) such subjects. Luminal IgA concentrations were significantly greater in subjects > or = 75 yr old with bacterial overgrowth than in culture-negative subjects (p < or = 0.003). CONCLUSIONS: Small intestinal overgrowth with colonic-type bacterial should be considered in subjects > or = 75 yr old with chronic diarrhea, anorexia, or nausea, even in the absence of clues such as clinically apparent predisposition or vitamin B12 deficiency. Small intestinal dysmotility, rather than fasting hypochlorhydria or mucosal immunosenescence, probably is responsible for the prevalence of bacterial overgrowth in this group.
Aged↗
Luminal antigliadin antibodies in small intestinal bacterial overgrowth.
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. Luminal total IgA and IgA-antigliadin antibody concentrations were measured by radial immunodiffusion and indirect enzyme immunoassay, respectively. Local mucosal counts of IgA-plasma cells were determined by immunohistochemistry. Small intestinal histology and intraepithelial lymphocyte counts were assessed by light microscopy. Corresponding serum antigliadin antibody concentrations were determined. RESULTS: SIBO was present in 17/26 (65.4%) subjects. No subject with SIBO had villous atrophy. Luminal total IgA concentrations (p < 0.0005), mucosal IgA-plasma cell counts (p < 0.01), and intraepithelial lymphocyte counts (p < 0.01) were significantly increased in subjects with SIBO. Luminal IgA-antigliadin antibodies were detected in 6/17 (35.3%) subjects with SIBO and 0/9 (0%) subjects without SIBO. Luminal IgA-antigliadin antibody concentrations correlated significantly with luminal total IgA levels (p < 0.01) but not with serum values (p < 0.1). Serum IgG-antigliadin antibody concentrations were elevated in 2/6 (33.3%) subjects with SIBO and positive luminal antigliadin antibodies. CONCLUSIONS: SIBO may be an alternative explanation to "latent" or "potential" celiac disease for positive luminal antigliadin antibodies in subjects with either normal or only mildly abnormal small intestinal histology, even when serum antigliadin antibody concentrations are elevated. Positive luminal antigliadin antibodies in SIBO probably occur as epiphenomena in the context of a graded mucosal immune response to local bacterial antigens.
Adult↗
Screening for colorectal cancer: too early to be dogmatic.
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Australia↗
Correlation of hydrogen and methane production to rice carbohydrate malabsorption in Burmese (Myanmar) children.
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. If an increased carbohydrate load in the colon due to rice malabsorption provides increased substrate for methanogenic bacteria in the left colon, higher fasting breath methane concentrations might be a simpler method of diagnosing rice malabsorption. We tested breath hydrogen and methane over a 4-h period and did anthropometric measurements in 142 subjects, 79 children, and 63 adults. Seventy percent of children were rice-malabsorbers. Methane production occurred in 20% of children under 5 years of age and increased to 60% of adults. There is an association of rice malabsorption with reduced length. There was not correlation between rice malabsorption and breath methane, and the concentration of breath methane does not, therefore, indicate rice absorption status and cannot replace rice breath hydrogen tests.
Adult↗
Patterns of methane production in a Burmese (Myanmar) population.
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 26.2 years. Half (49.8%) of the Myanmar population produced methane, this figure comprising 53% of females and 46% of males sampled. Methane production increases with age and reaches adult levels after 10 years of age. A high prevalence of methane production was found in children under 3 years of age (15.8%). Methane production was absent in 13 solely breast-fed children and increased as other food was introduced into the diet. There was an association of methane production within families and with smoking. The prevalence of methane production increased in male and female smokers, with 75% of smokers producing methane. Methane production was not associated with occupation, education, income, water source, latrine type, previous diarrhoea, antibiotic usage or socio-economic status.
Adolescent↗
Mucosal cytokine production in small-intestinal bacterial overgrowth.
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. This study addressed this issue. METHODS: Eighteen adult subjects were studies with culture of proximal small-intestinal luminal secretion and measurement of luminal interferon-gamma, interleukin-6, and tumour necrosis factor-alpha concentrations by enzyme-linked immunosorbent assay. Small-intestinal histology was assessed by light microscopy. RESULTS: Interferon-gamma, interleukin-6, and tumour necrosis factor-alpha were measurable in proximal small-intestinal luminal secretions of all subjects, even in the absence of light microscopic evidence of enteropathy. Small-intestinal bacterial overgrowth was present in 12 of 18 (66.7%) subjects. Luminal concentrations of neither interferon-gamma nor tumour necrosis factor-alpha differed significantly in subjects with and without small-intestinal bacterial overgrowth (P + 0.06 and P = 1.0, respectively). Conversely, luminal interleukin-6 concentrations were significantly increased in subjects with this disorder (P = 0.02). Multivariate linear regression analysis suggested that colonic-type rather than salivary-type flora mediated this increased interleukin-6 response (P = 0.02 and P = 0.64, respectively). No correlation was found between luminal interleukin-6 and tumour necrosis factor-alpha concentrations, even after the confounding influence of colonic-type bacteria was excluded (P = 0.60). CONCLUSIONS: These findings suggest that increased mucosal production of interleukin-6 occurs in small-intestinal bacterial overgrowth, particularly when the overgrowth flora includes colonic-type bacteria. Conversely, luminal levels of neither interferon-gamma nor tumour necrosis factor-alpha are increased in the circumstance, distinguishing the local cytokine profile in this disorder from those that occur in coeliac disease and inflammatory bowel disease.
Adult↗
The expression of complement protein 4 and IgG3 in luminal secretions.
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. Mucosal C4 immunoreactivity and the presence or absence of small-intestinal bacterial overgrowth were determined in all subjects. Caecal luminal concentrations of IgG3 and C4 were measured in a separate cohort of eight asymptomatic subjects. RESULTS: Proximal small-intestinal luminal C4 and IgG subclass concentrations were not significantly influenced by the presence of absence of small-intestinal bacterial overgrowth (P > 0.2). Nor did plasma C4 levels significantly influence C4 concentrations in small-intestinal luminal secretions (P > 0.2). Mucosal immunoreactivity for C4 was present in every subject. A significant correlation was found between C4 and IgG3 concentrations in proximal small-intestinal luminal secretions (P < 0.0005) and also in caecal secretions (P < 0.05) but not in peripheral blood (P > 0.1). CONCLUSIONS: Common factors, not including the presence or absence of small-intestinal bacterial overgrowth, regulate luminal concentrations of C4 and IgG3. Local investigation is mandatory when assessing mucosal immune mechanisms.
Cecum↗
Luminal immunity in small-intestinal bacterial overgrowth and old age.
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. IgG subclass, and IgD concentrations. IgA subclasses were measured in 24 unselected subjects. Serum immunoglobulin and salivary IgA concentrations were measured in all subjects. RESULTS: IgA2 and IgG3 were predominant IgA and IgG subclasses in proximal small-intestinal luminal secretions. Luminal concentrations of IgA2 and IgM, but not IgG3 or any other IgG subclass, were significantly increased in small-intestinal bacterial overgrowth, which was present in 19 of 33 (57.6%) subjects. Old age did not influence these levels. Luminal immunoglobulin concentrations did not correlate significantly with either serum or salivary values. IgD was not measureable in proximal small-intestinal secretions. CONCLUSIONS: Increased luminal concentrations of the secretory immunoglobulins, IgA2 and IgM, occur in small-intestinal bacterial overgrowth. Local investigation is mandatory when assessing the mucosal immunopathology of this disorder. Luminal IgG3 is unlikely to be predominantly derived from serum. Old age does not independently influence luminal immunity.
Age Factors↗
Cost benefit of early diagnosis of colorectal cancer.
In most Western countries, colorectal cancer is an important disease in terms of morbidity and mortality. As it has a premalignant asymptomatic stage in the form of benign adenomas that might be detected by screening, and as screening leads to detection of colorectal cancer at an earlier stage, there is potential for improved and better quality survival. Most cost-effective analyses rank the various screening strategies at less than an accepted benchmark value of approximately $40,000 per added year of life. Periodic colorectal screening is therefore a cost-effective intervention and the Office of Technology Assessment of the Congress of the United States has concluded that colorectal cancer screening in average-risk adults beginning at age 50 is a relatively good investment for society. Flexible sigmoidoscopy and double contrast barium enema are the most cost-effective strategies but they both require colonoscopy if a lesion is identified. Colonoscopy at 10-yearly intervals is of comparable cost to flexible sigmoidoscopy every 5 years and less costly than FSIG every 3 years. Combination strategies, using faecal occult blood testing with periodic flexible sigmoidoscopy or double contrast barium enema are as costly as colonoscopy. The choice of screening strategies needs to be tailored to the individual, and a process of community education is an essential prerequisite to the success of any programme.
Barium Sulfate↗
The lactulose breath hydrogen test and small intestinal bacterial overgrowth.
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. RESULTS: Sensitivity (16.7%) and specificity (70.0%) of the lactulose breath hydrogen test alone for small intestinal bacterial overgrowth were poor. Combination with scintigraphy resulted in 100% specificity, because double peaks in serial breath hydrogen concentrations may occur as a result of lactulose fermentation by cecal bacteria. Sensitivity increased to 38.9% with scintigraphy, because a single rise in breath hydrogen concentrations, commencing before the test meal reaches the cecum, may occur in this disorder. Sensitivity remained suboptimal irrespective of the definition of small intestinal bacterial overgrowth used, the nature of the overgrowth flora, favorable luminal pH, the presence of concurrent gastric bacterial overgrowth, or the in vitro ability of the overgrowth flora to ferment lactulose. CONCLUSIONS: Definitions of an abnormal lactulose breath hydrogen test based on the occurrence of double peaks in breath hydrogen concentrations are inappropriate. Not even the addition of scintigraphy renders this test a clinically useful alternative to culture of aspirate for diagnosing small intestinal bacterial overgrowth.
Bacterial Infections↗
Bacteriological method for detecting small intestinal hypomotility.
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. The reproducibility of bacteriological analyses of saliva and small intestinal secretions was determined in 12 subjects. RESULTS: Serial bacteriological analyses of saliva and proximal small intestinal secretions yielded reproducible results over time periods of up to 1 month. Eleven subjects were deemed to harbor Enterobacteriaceae of nonsalivary origin in proximal small intestinal secretions. Orocaecal transit, but not gastric emptying, of a liquid test meal was significantly delayed in this group (p = 0.002 and p = 0.84, respectively), suggesting the presence of small intestinal hypomotility. Impaired gastric acidity unlikely confounded assessment of the origin of small intestinal Enterobacteriaceae in any instance. CONCLUSIONS: The presence of Enterobacteriaceae of nonsalivary origin in proximal small intestinal secretions may be taken to reflect the presence of small intestinal hypomotility. The presence of impaired gastric acidity does not confound this approach. Because small intestinal intubation and culture of aspirate are required anyway to accurately diagnose small intestinal bacterial overgrowth, the simple addition of concurrent bacteriological analysis of saliva may allow small intestinal hypomotility to be detected at the same time as the presence or absence of small intestinal bacterial overgrowth itself is established, thus streamlining the investigation of subjects for this disorder and its possible causes.
Bacterial Infections↗
Helicobacter pylori and gastric neoplasia: evolving concepts.
There is evidence that Helicobacter pylori infection is associated with gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma and possibly with non-ulcer dyspepsia. Eradication therapy for confirmed H. pylori infection may therefore become mandatory in patients with non-ulcer dyspepsia severe enough to warrant endoscopy and in first-degree relatives of patients with gastric cancer. However, routine treatment of asymptomatic carriers awaits confirmation of the association with cancer.
Adenocarcinoma↗
Dyspepsia and esophageal reflux: an overview.
BACKGROUND: Dyspepsia is a major problem in the community with considerable morbidity. RESULTS: Appropriate therapy improves the quality of life of such patients and emphasizes the important role of diagnosis and management. The role of Helicobacter pylori is still to be defined, as does measurement of dysmotility. The management of reflux-like dyspepsia, in particular, assumes increasing importance in terms of cost-benefit.
Dyspepsia↗
Fasting breath hydrogen concentrations in gastric and small-intestinal bacterial overgrowth.
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. METHODS: Forty-two subjects underwent culture of gastric and duodenal aspirates. The pH was measured by indicator paper. Paired fasting breath hydrogen concentrations were measured by gas chromatography within 7 days of endoscopy. RESULTS: Paired fasting breath hydrogen concentrations differed in terms of normality or abnormality in 21% of subjects. Paired concentrations correlated significantly in overgrowth but not in culture-negative subjects. Sensitivity for bacterial overgrowth was 4-29%, and specificity 71-100%. No correlation with gastroduodenal pH was found. CONCLUSIONS: The clinical relevance of a single fasting breath hydrogen concentration is limited. The efficacy of paired measurements for gastric or small-intestinal bacterial overgrowth is poor.
Bacterial Infections↗