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Biomedical subjects

W G Brydon

Publications and source records attributed to W G Brydon.

At least 19 recordsLinked to original sources

Limitations of faecal elastase-1 and chymotrypsin as tests of exocrine pancreatic disease in adults.

BACKGROUND: The faecal enzymes elastase and chymotrypsin are a relatively inexpensive non-invasive means of investigating causes of malabsorption. However, such tests may be affected by enzyme degradation or faecal dilution. METHODS: Faecal elastase-1 and chymotrypsin were measured in 225 patients in whom pancreatic disease was suspected, and the association between faecal free water and pH with these faecal enzymes was examined in subjects with normal pancreatic function. RESULTS: The sensitivity of faecal elastase-1 and chymotrypsin for identifying exocrine pancreatic disease was 75% and 60%, respectively. Corresponding specificities for excluding disease were 95% and 97%. The positive predictive value for faecal elastase-1 increased from 58% to 92% when watery diarrhoea was excluded. Faecal elastase-1 (inversely) and chymotrypsin (directly) were significantly associated with percentage faecal free water content in subjects without pancreatic disease. Faecal elastase-1 was not related to faecal pH, whereas chymotrypsin was inversely related to pH. CONCLUSION: Faecal elastase-1 is a more sensitive test for exocrine pancreatic disease in adults but is affected by dilution in patients with watery diarrhoea. The value of faecal chymotrypsin is limited by intestinal degradation.

Adult↗

Assessment of faecal occult blood loss by qualitative and quantitative methods.

BACKGROUND: Various methods exist for the assessment of faecal occult blood loss in a patient with suspected gastrointestinal blood loss. METHODS: The present study examined the effectiveness and financial implications of a qualitative guaiac-based method (Haemoccult) of faecal occult blood detection and a quantitative measure of haeme-derived porphyrins (Hemoquant) in 184 patients who underwent assessment of faecal blood loss by both methods over a three year period during assessment of iron deficiency anaemia. MAIN FINDINGS: At least one Haemoccult test was positive in 72.2% of patients while Hemoquant was suggestive of significant blood loss (> 2mg haemoglobin/g faeces) in 29.9%. Patients underwent a total of 324 further endoscopic or radiological investigations of which 76.5% demonstrated no abnormality. A diagnosis was reached in 60 patients (32.6%). A significant potential source of gastrointestinal bleeding was found in 48 patients (26.1%). Hemoquant achieved a sensitivity of 62.5% and a specificity of 81.6% while with Haemoccult it was 85.4% and 32.4%, respectively. Hemoquant was normal in 18 patients with significant gastrointestinal conditions including peptic ulcers and colonic polyps. While Haemoccult only missed 7 lesions, two of these were colonic cancers. The quantitative nature of the Hemoquant test gave little clue as to diagnosis. CONCLUSION: Neither of the tests examined was ideal but Hemoquant had an overall better performance and further investigation of patients with evidence of blood loss from this test should be mandatory.

Adolescent↗

Serum 7 alpha-hydroxy-4-cholesten-3-one and selenohomocholyltaurine (SeHCAT) whole body retention in the assessment of bile acid induced diarrhoea.

OBJECTIVE: To assess the reliability of serum 7 alpha-hydroxy-4-cholesten-3-one (7 alpha-3ox-C) in the differential diagnosis of bile acid induced diarrhoea by comparison with 75selenohomocholyltaurine whole body retention (SeHCAT WBR). DESIGN: One hundred and sixty-four patients with chronic diarrhoea were investigated prospectively in two centres (Edinburgh and Sweden) by two different tests which measure bile acid loss or synthesis: the SeHCAT test which measures the 7-day SeHCAT WBR and serum 7 alpha-3ox-C which reflects the rate of bile acid synthesis. RESULTS: Forty-six patients had SeHCAT WBR of less than 10% (19 with ileal disease or resection, nine with idiopathic bile acid induced diarrhoea and 18 with miscellaneous causes for bile acid induced diarrhoea). All patients with ileal or idiopathic disease showed a favorable response to treatment as did 13 of the miscellaneous group. Serum 7 alpha-3ox-C was raised in all subjects with ileal disease/resection, seven patients with idiopathic disease and all subjects in the miscellaneous group who responded to treatment. Sixteen out of 118 patients with SeHCAT WBR greater than or equal to 10% had raised serum 7 alpha-3ox-C. CONCLUSION: The positive predictive value of serum 7 alpha-3ox-C was 74%. The high negative predictive value (98%) of serum 7 alpha-3ox-C indicates the possible use of this test for excluding bile acid malabsorption in this population. All but two subjects who responded to treatment had raised serum 7 alpha-3ox-C concentrations. The possibility that the sensitivity of the test can be improved by repeat testing needs to be further investigated. There was a significant correlation between fractional catabolic rate (FCR) SeHCAT and serum 7 alpha-3ox-C (r = 0.63, P < 0.0001). Further data are required to validate the reference range in women over 70 years of age.

Adolescent↗

Use of whole gut perfusion to investigate gastrointestinal blood loss in patients with iron deficiency anaemia.

Iron deficiency anaemia may be due to occult bleeding into the gut. However, although clinical investigations may show a high frequency of gastrointestinal tract disease in these patients, the cause-effect relationship between the lesions detected and anaemia remain uncertain. This study aimed to establish whether lesions detected by endoscopy or imaging of the gastrointestinal tract in patients with unexplained iron deficiency anaemia are bleeding continuously. Routine clinical tests were performed in 42 patients with unexplained iron deficiency anaemia referred to this unit. Whole gut lavage and assay of haemoglobin in the gut perfusate were also performed. The main outcome measures were clinical diagnoses (by imaging and endoscopy of the upper gastrointestinal tract and colon); the concentration of haemoglobin in whole gut lavage fluid; and the calculated gastrointestinal blood loss per day. There were 73 clinical, dietary, or iatrogenic factors of possible aetiological importance in the 42 patients--poor diet (10), gross gastrointestinal abnormality (34 in 28 patients), malabsorption (14), coagulation problems (6), and NSAID use (9). The gut lavage test showed, however, that at the time the test was performed, only eight patients were losing more than 2 ml blood daily into the gut, including all four with colonic cancer, one with diffuse gastric vascular ectasia, and one with severe ulcerative oesophagitis. It is concluded that occult gastrointestinal bleeding sufficient to cause anaemia was evident in only 19% of 42 patients. There was a high frequency of other potential causes of iron deficiency in the remainder, suggesting that most of the gastrointestinal diseases and lesions detected in them were probably coincidental. Factors other than blood loss should be considered and treated in patients referred for anaemia assessment.

Adult↗

Successful Helicobacter pylori eradication incorporating a one-week antibiotic regimen.

BACKGROUND: The optimum regimen for the eradication of Helicobacter pylori remains unclear. The aim of this study was to determine the efficacy and tolerability of omeprazole 40 mg daily given for 2 weeks, plus amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. given for the first 7 days, in the treatment of H. pylori associated peptic ulcer disease. RESULTS: One hundred and thirty-two consecutive patients with peptic ulcer disease were entered into the study (89 male, 41 female; median age 47 years; inter-quartile range: 36-58 years). H. pylori was eradicated successfully in 109 of 130 patients (intention-to-treat: 83%; 95% confidence limits: 76-89%); per protocol: 85% (95% CI: 78-91%)). Ninety per cent of patients completed the full course of therapy. Only four patients (3%) stopped treatment as a result of side effects although these occurred in 41% of patients. One patient developed pseudomembranous colitis requiring hospital admission. CONCLUSION: Omeprazole combined with one week of treatment of amoxycillin and metronidazole is an effective and well tolerated Helicobacter eradication regimen. Occasional severe side effects remain a risk, even when the duration of antibiotic exposure is reduced.

Adult↗

Use of whole-gut lavage to measure intestinal immunity in healthy Sierra Leonean children.

In view of the potential roles of intestinal immunodeficiency and hypersensitivity in the infection/diarrhea/malnutrition cycle, we need a safe and ethical method to study intestinal immunity of children in the developing world. Work in adults has shown that the fluid obtained by whole-gut lavage (WGLF), essentially a gut perfusate, can be used to assess intestinal immunity, inflammation, and gut losses of protein and blood. Gut lavage was successfully performed in 24 of 25 "normal" children aged 6-9 years, from Freetown, Sierra Leone, with parental informed consent. WGLF was treated with protease inhibitors, stored at -20 degrees C, and transferred to Edinburgh for laboratory studies. These showed that no child had occult blood loss but four had evidence of protein-losing enteropathy. Compared with values for Scottish adults, WGLF from the Sierra Leonean children had significantly higher concentrations of IgA and IgM and of IgA and IgM antibodies to dietary antigens and to Salmonella typhi lipopolysaccharide. In three children, very low levels of IgA and IgA antibody were present: Two of these were the only cases with detectable sIL2R in lavage fluid, indirect evidence of intestinal T cell activation; tumor necrosis factor was not detectable. Substantial information on childrens' intestinal immunity can be obtained by the method described.

Antibodies, Bacterial↗

Fermentation and subsequent disposition of 14C-labelled plant cell wall material in the rat.

A 14C-labelled plant cell wall preparation (14C-PCW) produced from spinach (Spinacia oleracea L.) cell culture exhibits uniform labelling of the major polysaccharide groups (%): pectins 53, hemicellulose 13, cellulose 21, starch 3. This 14C-PCW preparation has been used in rat studies as a marker for plant cell wall metabolism. Metabolism of the 14C-PCW occurred largely over the first 24 h. This was due to fermentation in the caecum. The pectic fraction of the plant cell walls was degraded completely in the rat gastrointestinal tract, but some [14C]cellulose was still detected after 24 h in the colon. Of the 14C, 22% was recovered in the host liver, adipose tissue and skin, 26% excreted as 14CO2 and up to 18% was excreted in the faeces. There was no urinary excretion of 14C. In vitro fermentation using a caecal inoculum showed reduced 14CO2 production, 12% compared with 26% in the intact rat. 14C-PCW is a useful marker to investigate the fate of plant cell wall materials in the gastrointestinal tract. These studies show both bacterial fermentation of the 14C-PCW and host metabolism of the 14C-labelled fermentation products.

Animals↗

The influence of wheat bran and pectin on the distribution of water in rat caecal contents and faeces.

Wheat bran and pectin (100 g/kg) were added to a basal diet and fed to rats. An in vitro dialysis technique was used to measure the distribution of caecal and faecal water between the bound, i.e. that held by bacteria and undigested macromolecules, and free water. Bran increased wet (67%) and dry (74%) faecal weight. Pectin increased wet faecal weight (59%), but did not influence dry weight. In faeces both bran and pectin increased the amount of total and bound water, but only pectin increased total and bound water when expressed on a dry weight basis. Caecal wet (90%) and dry (67%) weights increased with pectin but not with bran. Bran did not change total water but increased bound water whereas pectin increased both. This suggests that water contributed more to the increase in stool bulk in the pectin-supplemented animals due to free and bound water associated with both increased numbers of bacteria and residual pectin. Pectin altered the distribution of water in faeces. Bran has no effect on water distribution and is only partly fermented. The residual water-holding capacity leads to an increased wet and dry stool output.

Animals↗

Haemoglobin in gut lavage fluid as a measure of gastrointestinal blood loss.

To detect and measure occult gastrointestinal bleeding, we have measured haemoglobin concentrations (by HemoQuant) in the clear fluid obtained after whole-gut lavage. In subjects with healthy gastrointestinal tracts, lavage-fluid haemoglobin concentrations were 0.5-5.1 mg/L, equivalent to daily blood loss of 0.1-1.1 mL. High concentrations were found for patients with colorectal cancer, severe diverticular disease, and rectal varices, in seven of sixteen patients with active inflammatory bowel disease, and in four patients with iron-deficiency anaemia thought to be due to gastrointestinal bleeding. In these four patients, estimated blood loss ranged from 2.6-24.5 mL per day. This method could have various research and clinical applications.

Barium Sulfate↗

The effects of ispaghula on rat caecal fermentation and stool output.

The colonic fermentation of ispaghula, a mucilage from Plantago ovata composed mainly of arabinoxylans, and its effects on stool output and caecal metabolism were investigated. Four groups of eight rats were fed on a basal diet (45 g non-starch polysaccharides/kg) for 28 d. The diet was then supplemented with ispaghula (g/kg; 0, 5, 15 or 50) for 28 d. Ispaghula increased stool dry weight and apparent wet weight but faecal water-holding capacity (amount of water held per g dry faecal material at 0.2 mPa) was unchanged. The extent of faecal drying in the metabolism cages was measured for rats fed on the basal diet and 50 g ispaghula/kg diet. At the faecal output levels encountered, only an 8% loss of wet weight would be predicted over 24 h and this was independent of diet. Faecal short-chain fatty acid (SCFA) concentration did not change but SCFA output increased. The molar proportion of SCFA as propionic acid increased and faecal pH was reduced. Values from pooled faecal samples suggested that approximately 50% of the ingested ispaghula was excreted by the 50 g ispaghula/kg diet group. Diaminopimelic acid (a constituent of bacterial cells) concentrations fell but output was unchanged indicating no change in bacterial mass. Similar changes were seen in the caecal contents but caecal pH and SCFA were unaffected. Ispaghula increased both caecal and colonic tissue wet weight and colonic length. Our results suggest that ispaghula is partly fermented in the rat caecum and colon, and loses its water-holding capacity. However, it is still an effective stool bulker and acts mainly by increasing faecal water by some unknown mechanism.

Animals↗

The effect of weaning diet on the subsequent colonic metabolism of dietary fibre in the adult rat.

The effect of the weaning diet on the subsequent colonic metabolism of bran and pectin in the adult rat has been investigated. Feeding a fibre-reduced diet on its own or supplemented with bran (WB) and pectin (P) from weaning (fibre-reduced (weaning)) was compared with introducing the same diet to age-matched rats reared on a standard laboratory diet from weaning (fibre-reduced (6 weeks)). The effects of the diets on colonic metabolism were measured by wet and dry caecal contents and stool weights, caecal sac weight, and caecal and faecal short-chain fatty acids (SCFA). Final body-weights were greater for fibre-reduced (6 weeks) and fibre-reduced (6 weeks) + P groups, but not fibre-reduced (6 weeks) + WB, than those of the fibre-reduced (weaning) rats. Rats fed on fibre-reduced (6 weeks) diet had a higher total caecal SCFA content than fibre-reduced (weaning) control rats. Fibre-reduced (weaning) + P-fed rats had a threefold higher caecal concentration of both propionate and butyrate than the matched fibre-reduced (6 weeks) + P group. Fibre-reduced (weaning) + WB animals had a significantly higher butyrate caecal concentration compared with their matched fibre-reduced (6 weeks) + WB group. Fibre-reduced (weaning) + P-fed rats had a lower faecal output than the fibre-reduced (6 weeks) + P rats. There was no difference in faecal output in rats fed on either fibre-reduced (6 weeks) + WB or fibre-reduced (weaning) + WB. The faecal concentration of SCFA was in general higher in the rats fed on fibre-reduced (weaning) alone, + P, or + WB than in those fed on fibre-reduced (6 weeks) alone, + P or + WB. Faecal output of total and individual SCFA was increased on the fibre-reduced (weaned) + WB diet compared with fibre-reduced (6 weeks) + WB-fed animals. The diet at weaning may be important in determining the pathways of caecal bacterial metabolism in the adult rat. In studying the effect of a dietary fibre on caecal metabolism and faecal output, when the diet is changed appears to be important.

Animals↗

Laxative induced diarrhoea--a neglected diagnosis.

A laxative screening service was established and offered to gastroenterologists in hospitals covering the West and Central belt of Scotland. The prevalence of laxative induced diarrhoea was assessed in two populations and was found to be 4% in new patients presenting to a gastroenterology clinic with diarrhoea and 20% in patients already under investigation of chronic idiopathic diarrhoea. A high rate of missed diagnosis of laxative induced diarrhoea (71%) and a low request rate (eight per annum) confirm the low clinical awareness of this diagnosis. We found potential savings of 80% of the cost of investigations subsequently ordered which could have been avoided by performing laxative screens on all patients presenting with diarrhoea. The introduction of such a screening policy is recommended as a cost-effective measure.

Cathartics↗

Dietary fiber: in vitro methods that anticipate nutrition and metabolic activity in humans.

Gravimetric measurement of dietary fiber (DF) gives no indication of the biological function of any particular fiber. This study describes simple methods based on dialysis and fermentation that enable a hierarchy of fibers to be described for each of the major actions of fiber along the gastro-intestinal tract: nutrient absorption, sterol metabolism, cecal fermentation, and fecal bulking. These results were compared with previous metabolic studies with the same fiber isolates in humans. DF that modifies nutrient absorption can be identified by using dialysis studies, whereas identifying DF that modifies sterol metabolism, cecal fermentation, and fecal weight requires formulas that incorporate dialysis and fermentation results. Results from dialysis and fermentation predicted the action of wheat bran, pectin, guar, gum arabic, carboxymethylcellulose, gellan, tragacanth, xanthan, and karaya in humans and generated anomalous results for karaya and tragacanth. These methods could form the basis of techniques that would enable a screening of novel and processed fibers before studies in animals, including humans.

Bile Acids and Salts↗

Fermentation of wheat bran and gum arabic in rats fed on an elemental diet.

1. Gum arabic and wheat bran were added to an elemental diet (100 g/kg) in order to study their metabolism in the caeca of adult male albino Wistar rats. 2. Dry stool weight (g/d) over 12 weeks was 0.70 (SE 0.05) on the elemental control diet. Wheat bran increased mean dry stool weight to 1.09 (SE 0.08), an increase of 56%. There was no significant difference between faecal weights (0.65 (SE 0.08)) of the gum-arabic-supplemented group and the unsupplemented group. 3. Wet caecal-sac weight, dry caecal-contents weight, and faecal and caecal bacterial mass (measured by 2,6-diaminopimelic acid) all increased significantly with the gum-arabic-supplemented diet but not with the wheat-bran-supplemented diet. 4. Total short-chain fatty acids (mostly acetate) increased in the caecum and faeces with the gum-arabic-supplemented diet but not with the wheat-bran-supplemented diet. 5. Breath hydrogen and methane production decreased to negligible amounts over the 12 weeks of the experiment.

Animals↗