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Biomedical subjects

S Radley

Publications and source records attributed to S Radley.

31 records · Page 2Linked to original sources
PubMed1994

Unconjugated faecal bile acids in familial adenomatous polyposis analysed by gas-liquid chromatography and mass spectrometry.

Previous studies have suggested reduced formation of secondary bile acids in patients with familial adenomatous polyposis (FAP). Developments in the collection, extraction and analysis of faecal bile acids as well as in the accurate diagnosis of FAP by DNA markers prompted reinvestigation of this hypothesis. The median (interquartile range (i.q.r.)) faecal bile acid concentration (3.69 (1.66-5.36) mumol per g dry weight) and daily excretion rate (60.5 (29-149) mumol per g per 24 h) in ten patients with FAP were similar to those of nine control subjects (3.31 (0.65-8.38) mumol per g dry weight and 30.1 (7.9-228) mumol per g per 24 h). Although the median (i.q.r.) concentration of only one bile acid (12-oxo-lithocholic acid) was significantly different between patients with FAP and controls (49 (34-70) versus 0 (0-20) nmol per g dry weight, P = 0.006), the derivatives of chenodeoxycholic acid (3.35 (1.76-5.32) versus 0.51 (0.13-2.37) mumol per g dry weight, P = 0.02) and cholic acid (1.63 (0.42-2.34) versus 0.80 (0.13-3.57) mumol per g dry weight, P = 0.006) were increased in those with polyposis. These results show increased bacterial biotransformation of faecal bile acids in patients with FAP.

Adenomatous Polyposis Coli↗
PubMed1994

Lipid peroxidation and prostaglandins in colorectal cancer.

Dietary fat, arachidonic acid metabolism and lipid peroxidation have all been implicated in colorectal carcinogenesis. Fatty acids, prostaglandins (PGE2, PGF2 alpha) and malondialdehyde (MDA), the stable end-product of lipid peroxidation of polyunsaturated fatty acids (PUFAs), were studied in paired tumour and normal mucosa of 20 patients with colorectal cancer. Levels of arachidonic acid and total PUFAs were increased in the phospholipid fraction of tumours (P < 0.05). Levels of PGE2 and MDA were also higher in tumours (P < 0.001) and there was a significant correlation between MDA and PGE2 concentrations (rs = 0.69, P < 0.01). In contrast to previously reported in vitro studies, this work suggests that lipid peroxidation may be enhanced in human colorectal tumours. As PGE2 and MDA have been shown to be involved in carcinogenesis, these may be considered potential therapeutic targets for preventing or treating colorectal carcinoma.

Aged↗
PubMed1994

Mucosal concentration and excretion of clindamycin by the human stomach.

Each of 12 patients undergoing routine diagnostic upper gastrointestinal endoscopy received a single iv infusion of clindamycin phosphate 300 mg over 10 min. During the endoscopy, mucosal biopsies of the gastric antrum and fundus were obtained at varying times following the infusion. The clindamycin concentrations in the biopsies and in serum samples also taken after the infusion were determined. In addition, six healthy volunteers participated in a cross-over study on two different days. On both days, each subject received a single iv infusion of clindamycin phosphate 300 mg, immediately after which, gastric secretion was stimulated by iv pentagastrin (2 micrograms/kg/h) which was infused continuously over 150 min. On one of the study days, acid secretion by the stomach was inhibited by a slow iv infusion of ranitidine 50 mg. Clindamycin concentrations in gastric aspirates and serum samples collected after the infusion were determined. Concentrations of clindamycin in the fundal mucosa were significantly higher than the simultaneous serum concentrations (median ratio of tissue concentration to serum concentration, 2.0; P < 0.005) while concentrations in the antral mucosa were similar to those in serum (median ratio, 1.2; P = 0.65). Ranitidine significantly inhibited pentagastrin-stimulated acid secretion as demonstrated by a decrease in the volume of gastric aspirate when ranitidine was administered compared with when it was not administered (P < 0.01). Clindamycin concentrations in gastric juice were approximately one and one-half times higher than those in serum samples obtained simultaneously, both during stimulation of gastric acid secretion with pentagastrin and during inhibition of pentagastrin-stimulated acid secretion with ranitidine. Gastric juice concentrations of clindamycin were significantly higher following administration of ranitidine than after stimulation of gastric secretion by pentagastrin alone. Fundal mucosal and gastric juice concentrations of clindamycin exceeded the hypothetical maximum serum concentrations, indicating that accumulation in the stomach occurred against a concentration gradient.

Adult↗
PubMed1993

Analysis of faecal neutral sterols in patients with familial adenomatous polyposis by gas chromatography-mass spectrometry.

Previous studies have suggested that patients with familial adenomatous polyposis (FAP) have increased faecal excretion of cholesterol but a reduction in cholesterol metabolites. It was consequently proposed that the degree of faecal cholesterol degradation could be used as a means of diagnosis. Developments in the extraction and analysis of faecal neutral sterols as well as the accurate means of diagnosing FAP by DNA analysis and indirect ophthalmoscopy has necessitated a re-examination of this proposal. Faecal neutral sterols were analysed in 10 patients with untreated FAP following a complete 5-day stool collection and compared with 9 healthy control subjects (including 4 siblings) closely matched for age and sex. The median [25 and 75, percentiles] stool wet weights were similar between the FAP (97.5 [69, 192] g.24 h-1) and the control (116 [61.5, 137] g.24 h-1) groups. Faecal cholesterol concentration was similar in the two groups (FAP = 2.3 [1.4, 4.2]; control = 3.5 [1.0, 6.0] mumol.g-1 dry wt) as was the concentration of total neutral sterols not including plant sterols (FAP = 17.2 [13.4, 21.0]; control = 18.2 [7.4, 21.6] mumol.g-1 dry wt). There were no significant differences in the proportions of cholesterol metabolised between the FAP (82.3 [74.2, 93.5]%) and control (72.1 [5.7, 81.3]%) groups. This study does not support the notion that faecal neutral sterol metabolism is uniquely different in patients with FAP.

Adenomatous Polyposis Coli↗
PubMed1993

Detection of colorectal cancer by faecal alpha 1-antitrypsin.

Alpha 1-antitrypsin was measured in 5-day faecal collections from patients with colorectal cancer or adenomatous polyps and a symptomatic control group. Collections were homogenized and lyophilized prior to measurement of alpha 1-antitrypsin by radial immuno-diffusion. Colorectal cancer dry weight concentrations were significantly higher than the symptomatic control results, with 57% having results greater than 95% normal values of this control group. There was no significant difference between adenomatous polyp dry weight concentrations and symptomatic control results. Wet weight concentrations were calculated from wet/dry ratios. Colorectal cancer wet weight concentrations were significantly higher than symptomatic control results with 48% having results greater than 95% normal values of this control group. Alpha 1-antitrypsin was also measured in non-lyophilized samples from an asymptomatic control group (n = 39). Colorectal cancer wet weight concentrations were significantly higher than asymptomatic control results, with 62% having results greater than 95% normal values of this control group. Faecal alpha 1-antitrypsin measurement deserves further assessment for use in detecting colorectal cancer.

Adenoma↗
PubMed1993

Endoscopic sphincterotomy for acute pancreatitis.

There is now considerable evidence linking the severity of gallstone-associated acute pancreatitis with obstruction to both the bile duct and the pancreatic duct by "persisting" stones either because of continuous or repeated impaction, or repeated passage. Two prospective trials have shown endoscopic sphincterotomy to be superior to other forms of treatment, but only in severe cases, and general experience now extends to over 1000 cases so treated. Endoscopic sphincterotomy is also very effective in acute pancreatitis associated with acute cholangitis. Prophylactic endoscopic sphincterotomy may be of benefit in elderly patients in preference to prophylactic cholecystectomy. Yet to be fully explored is the role of this procedure in the early treatment of severe non-gallstone pancreatitis and in established pancreatic necrosis.

Acute Disease↗
PubMed1992

Faecal unconjugated bile acids in patients with colorectal cancer or polyps.

The unconjugated faecal bile acid profiles of 14 patients with colorectal cancer, nine patients with polyps and 10 controls were compared using gas liquid chromatography, controlling for such confounding variables as cholecystectomy, gall stones and hepatic function. Patients with adenomatous polyps had a higher concentration of faecal bile acids (5.23 mumol/g, 2.16-13.67 (median, range) v 1.96, 0.91-6.97; p = 0.016) lithocholic acid (2.41, 0.88-3.22 v 1.07, 0.38-2.03; p = 0.013) and total secondary bile acids (5.23, 2.16-13.4 v 1.96, 0.73-6.63; p = 0.02) compared with control subjects. Patients with colorectal cancer had an increased (p = 0.029) proportion of secondary faecal bile acids (mol%) compared with controls (100, 96.5-100 v 95.19, 81.73-100) and the ratios of the primary bile acids, cholic and chenodeoxycholic acid, to their respective derivatives (secondary bile acids) were significantly lower in cancer patients compared with control and patients with polyps (p = 0.034 to 0.004). This study lends further support to the theory that bile acids may play a role in the development of polyps and colorectal cancer.

Adenocarcinoma↗
PubMed1990

Effect of alcohol and alcoholic beverages on meal-stimulated pancreatic secretion in humans.

Alcohol and alcoholic beverages may have different effects on pancreatic secretion and hormone release in humans. To test this hypothesis we studied the effects of an alcohol solution and a glucose solution and compared them with those of alcoholic beverages on postprandial pancreatic secretion and release of gastrin, trypsin, and cholecystokinin in 6 healthy nonalcoholic male volunteers. Pancreatic enzyme secretion was measured in duodenal aspirate, plasma trypsin, and gastrin by radioimmunoassay and cholecystokinin by bioassay. The meal plus glucose significantly stimulated pancreatic enzyme secretion, release of gastrin and cholecystokinin, and caused no changes in plasma trypsin. The alcohol solution and all beverages added to the meal caused similar increases in alcohol blood levels and significantly less pancreatic enzyme secretion compared with the meal plus glucose. Plasma trypsin levels remained unchanged. Compared with the meal plus glucose, wine and beer caused a significantly higher release of gastrin, and beer also released significantly more cholecystokinin. Inhibition of pancreatic enzyme secretion stimulated by a meal in nonalcoholics is a common effect of alcohol and alcoholic beverages despite some differences on release of gastrointestinal peptides. This effect may have some implications in the pathogenesis of alcoholic pancreatitis.

Adult↗
PubMedDate not supplied

Comparability of hamster with human faecal unconjugated bile acids in a model of colorectal cancer.

The relationship between experimental colorectal carcinogenesis and bile acids has usually been investigated in the rat, a species with a markedly different bile acid profile from man. In this study, we show that the hamster faecal bile acid profile is similar to that in man. Rectal cancer was induced in hamsters using twice weekly instillations of N-methyl-N-nitro-N-nitrosoguanidine (MNNG) for 4 weeks at doses of 1-8 mg kg-1. The medcian (range) faecal bile acid concentrations of tumour-bearing hamsters (0.52, 0.46-0.84 mumoles g-1 faeces) was reduced compared to controls (1.08, 0.95-1.65, mumoles g-1) and non-tumour bearing MNNG treated hamsters (1.18, 0.64-1.42 mumoles g-1), largely due to a decrease in cholic acid derivatives (all p less than 0.05) at least). This model may be more suitable for studying the relationship between colorectal cancer and bile acids.

Animals↗