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Biomedical subjects

T C Northfield

Publications and source records attributed to T C Northfield.

At least 91 records · Page 5Linked to original sources
PubMed1990

Surface hydrophobicity of gastric mucosa in peptic ulcer disease. Relationship to gastritis and Campylobacter pylori infection.

The hydrophobicity of biopsy specimens of gastric mucosa in 228 dyspeptic subjects undergoing diagnostic endoscopy was assessed by measuring the plateau-advancing contact angle of saline drops using a goniometer. Subjects with duodenal ulcers (n = 49) and gastric ulcers (n = 17) had significantly lower mean contact angles than controls (n = 124) without ulcer (57 degrees in duodenal ulcer, 59 degrees in gastric ulcer vs. 66 degrees in controls; p less than 0.0001). There was no change in contact angle after healing with H2-receptor antagonists by comparison with pretreatment (59 degrees vs. 56 degrees for duodenal ulcer, n = 15; 57 degrees vs. 59 degrees for gastric ulcer, n = 5). Controls with gastritis had lower contact angles than those without (61 degrees, n = 50, vs. 70 degrees, n = 63; p less than 0.0001). The presence of Campylobacter pylori was associated with a significant decrease in contact angle in controls (59 degrees, n = 39, vs. 70 degrees, n = 75; p less than 0.0001).

Biopsy↗
PubMed1990

Thermodynamic effects of bile acids in the stomach.

The surface thermodynamic effects of bile acids in the stomach were assessed in 48 subjects who had undergone gastric surgery for peptic ulcer disease and in 52 controls with medically healed ulcers. We derived values for surface tension of gastric mucosa from contact angle using a goniometer and measured the surface tension of gastric juice by the drop-weight method. Subjects with gastric surgery had higher median fasting bile acid concentrations than controls (1.2 vs. 0.1 mmol/L; P less than 0.0001), higher mean mucosal surface tension (51.9 vs. 47.9 mN/m; P less than 0.0001), and lower mean surface tension of gastric juice (43.2 vs. 51.7 mN/m; P less than 0.0001). Subjects who had had a Billroth II gastrectomy (n = 19) had higher bile acid concentrations (5.8 vs. 0.6 mmol/L; P less than 0.01), higher mucosal surface tension (53.7 vs. 50.3 mN/m; P less than 0.05), and lower gastric juice surface tension (41.3 vs. 47.1 mN/m; P less than 0.05) than those who had a vagotomy and drainage procedure (n = 17). Overall, intragastric bile acid concentration correlated directly with surface tension of gastric mucosa (r = 0.51, P less than 0.0001) and inversely with that of gastric juice (r = -0.60, P less than 0.0001). In conclusion, the interfacial energy barrier at the surface of the gastric mucosa is overcome in the presence of intragastric bile acids.

Bile Acids and Salts↗
PubMed1990

Three different methods of inhibiting lipolysis in human chyme in vitro: efficiency and effect on phase distribution of lipids.

1. The efficiencies of three different methods of inhibiting fatty acid production in chyme have been evaluated. The effects of each method on the phase distribution of fatty acids after ultracentrifugation have been studied. 2. Chyme fatty acid concentrations were measured during a 4 h incubation (a) without an inhibitor, (b) after acid treatment, (c) after addition of p-bromophenylboronic acid and (d) after heating. 3. In a separate experiment, fresh chyme was incubated to allow equilibration of lipolysis. Aliquots were treated by each inactivation method and ultracentrifuged overnight to separate the phases. Total and micellar fatty acids and glycerides were measured. 4. In the first experiment, acid treatment completely inhibited fatty acid generation producing 4 h concentrations which were 93.4 +/- 5.6% (mean +/- SEM) of initial values compared with 398.0 +/- 54.0% (P less than 0.05) for uninhibited samples. p-Bromophenylboronic acid and heating gave significant but incomplete inhibition (132.9 +/- 6.6% and 166.1 +/- 15.2% of initial concentrations, respectively). 5. Ultracentrifugation disclosed five phases in all except the acid-treated samples, which had four. Micellar phase fatty acid concentrations were significantly higher in the acid-treated than in the untreated samples (2.6 +/- 0.7 versus 1.7 +/- 0.5 mmol/l, P = 0.05), as were glyceride concentrations (1.5 +/- 0.4 vs 0.6 +/- 0.3 mmol/l, P = 0.05). 6. It was concluded that acid treatment was the most efficient inhibitor of fatty acid production, but it disrupted the phases. p-Bromophenylboronic acid gave significant inhibition without causing phase disruption and was therefore the most useful inhibitor overall.

Bile Acids and Salts↗
PubMed1990

Occupational and socioeconomic factors associated with peptic ulcer and with cancers following consequent gastric surgery.

Over 3000 patients, treated surgically for peptic ulcers, were assigned to a Social Class and Occupation Group using information obtained either from their death certificates or from their hospital notes. An analysis of the relationship of socioeconomic status and occupation with the site of original ulcer and the risk of cancer is reported. The major observations were: (a) an association of gastric ulcer with manual and of duodenal ulcer with non-manual Social Class; (b) an association of gastric cancer with dusty occupation and colorectal cancer with professional and managerial workers; and (c) no association between post-surgery gastric cancer risk and social class. This implies that the early stages of gastric carcinogenesis are related to poor socioeconomic conditions but the progression from the precursor lesion (in this case gastric ulcer) to gastric cancer is not, and is consistent with the multistage hypothesis of gastric carcinogenesis proposed by Correa [Diet and Human Carcinogenesis (Edited by Joosens, J. V., Hill, M. J. and Geboers, J.), pp. 109-115. Excerpta Medica, Amsterdam (1985)].

Colorectal Neoplasms↗
PubMed1990

Effect of ursodeoxycholic acid (UDCA) on pancreatic enzyme secretion and gallbladder emptying.

We have used a duodenal perfusion technique to study the effect of chronic administration of ursodeoxycholic acid (UDCA) on postprandial pancreatic enzyme secretion and gallbladder emptying. Duodenal output and hepatic secretion rate of bile acid were also measured. Six gallstone subjects were studied during an evening meal and an overnight fast before and during UDCA administration (675 mg/day for 6 weeks). During the first postprandial hour, the duodenal trypsin output was reduced from 253 to 164 IU/kg/h (p less than 0.05), and mean gallbladder ejection fraction from 38 to 20% (p less than 0.05). The peak response to the meal was delayed from 30 to 50 min for trypsin output (NS) and from 25 to 45 min for gallbladder ejection fraction (p less than 0.05). Area under the curve during the first postprandial hour was decreased for trypsin output from 225 to 119 IU/kg (p less than 0.025), and for gallbladder ejection fraction from 43 to 19% (NS); but areas for the second postprandial hour were increased, so that total values were unchanged. We conclude that the pattern of response for both end organs during chronic UDCA is better described as an attenuated response to food, rather than as a simple reduction in response; and that, since the effects were unaccompanied by any quantitative changes in hepatic bile acid secretion rate, they were probably mediated via the qualitative change in biliary bile acid composition known to accompany chronic UDCA administration.

Aged↗
PubMed1990

Review article: bile acid therapy.

Over the past 3 years there has been a renewed interest in bile acid therapy not only because of the promising results obtained by combining this therapy with extracorporeal shock-wave lithotripsy for rapid gallstone dissolution, but also because of its novel use as a treatment for primary biliary cirrhosis. This article reviews the use of bile acids for both these indications.

Bile Acids and Salts↗
PubMed1990

Hepatic biliary lipid secretion and gall bladder biliary lipid mass in gall stone patients: effect of ursodeoxycholic acid.

We have carried out overnight measurements of hepatic secretion rate and duodenal output of biliary lipids using a duodenal perfusion technique. We correlated these measurements with the fasting state mass of biliary lipids within the gall bladder on the following morning using a combined nasoduodenal intubation and isotope scanning technique. We studied six gall stone subjects before and during treatment with ursodeoxycholic acid 675 mg/day. Lipid mass within the gall bladder correlated with the corresponding overnight hepatic secretion rate for all three biliary lipids. During ursodeoxycholic acid treatment, there was an increase in gall bladder bile acid mass without significant change in cholesterol or phospholipid mass. We conclude that the mass of individual biliary lipids within the fasting gall bladder is influenced by overnight hepatic biliary lipid secretion rate; and that the effect of ursodeoxycholic acid (675 mg/day) on cholesterol saturation index of fasting gall bladder bile is mediated via an increase in bile acid mass rather than through a decrease in cholesterol mass within the gall bladder.

Aged↗
PubMed1990

Enprostil, a prostaglandin E2 analogue, in the treatment of gastric ulcer--a multicentre comparison with pirenzepine.

In a double-blind, multicentre study 77 patients with benign gastric ulcer were randomly allocated to treatment with either enprostil 35 micrograms bd or pirenzepine 50 mg bd. After four weeks of treatment 13/26 (50 per cent) of evaluable enprostil-treated patients and 9/30 (30 per cent) of evaluable pirenzepine-treated patients were healed. Corresponding healing figures after eight weeks were 20/25 (80 per cent) and 25/31 (81 per cent). Both drugs rapidly reduced the severity of ulcer pain and the need for antacid use. No statistically significant differences were detected between the treatments with respect to healing rate or symptom control. Adverse events were reported by eight patients taking enprostil and by 17 patients taking pirenzepine. Two patients withdrew from each treatment group because of adverse events. None of these was serious. In conclusion, enprostil and pirenzepine were equally effective in healing gastric ulcers and no statistically significant differences in safety and efficacy were detected. There was a tendency for earlier healing and fewer side effects in the enprostil-treated patients.

Adolescent↗
PubMed1989

Measurement of the surface hydrophobicity of human gastrointestinal mucosa.

A technique has been developed for assessing the surface hydrophobicity of human gastrointestinal mucosa by measuring the plateau contact angle of saline drops applied to endoscopic biopsy specimens. The plateau contact angle was not affected by the mode of drying. The intraobserver and interobserver coefficient of variation was less than 5%. The gastric mucosal surface had a higher mean contact angle than the submucosal surface (69 degrees vs. 47 degrees, p less than 0.001). Glycerol drops gave lower contact angles than saline drops (55 degrees vs. 69 degrees) but gave the same derived values for surface free energy (42 vs. 41 mJ/m2). Regional values for contact angle were as follows: gastric body 70 degrees, antrum 70 degrees, duodenal bulb 62 degrees (p less than 0.01 vs. stomach), distal duodenum 50 degrees (p less than 0.001 vs. stomach and p less than 0.01 vs. bulb), and rectum 57 degrees (p less than 0.001 vs. stomach). We conclude that it is feasible to measure the surface hydrophobicity of human endoscopic biopsy specimens and that the stomach is relatively more hydrophobic than the duodenum and rectum.

Adult↗
PubMed1988

Mortality from colorectal and breast cancer in gastric-surgery patients.

In a preliminary "years at risk" analysis of 5018 patients treated surgically for peptic ulcer at St. James Hospital, Balham, between 1940 and 1960, there was an increase in mortality from colorectal cancer 20 or more years after operation (1.6 fold; p less than 0.05) and an increase in mortality from breast cancer (4.0 fold; p less than 0.001). During the first 20 post-operative years there was an apparent decrease in mortality from both cancers (relative rate = 0.7 (NS) for colorectal and 0.5 (p less than 0.01), for breast cancer). The excess risk of colorectal cancer after a 20 year latency was almost entirely due to the 9.5 fold (p less than 0.001) excess risk in the 381 female gastric ulcer patients treated by Billroth I operation, and the 8.0 fold (p less than 0.05) excess mortality for the small group of 123 female patients who had vagotomy for duodenal ulcer. The apparent decreased risk during the first 20 post-operative years was entirely due to the 5-fold decrease (p less than 0.01) in risk in the 659 male patients treated by Billroth I surgery for gastric ulcer. The ratio of colon: rectal cancers was very much higher in gastric ulcer than in duodenal ulcer patients (5.6 compared to 1.8) and higher in females than in males (6.0 compared to 2.4). The excess risk of breast cancer after a 20 year latency was 4-fold in both gastric ulcer and duodenal ulcer patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1988

Maintenance of hepatic bile acid secretion rate during overnight fasting by bedtime bile acid administration.

We have tested the hypothesis that the greater clinical efficacy of bedtime administration of bile acid in gallstone dissolution is due to prevention of the reduction in hepatic bile acid secretion that normally accompanies overnight interruption of the enterohepatic circulation, thus also reducing the secretion of supersaturated hepatic bile. We measured the hepatic bile acid secretion rate by combining duodenal perfusion of a nonabsorbable recovery marker (polyethylene glycol) with continuous intravenous infusion of a hepatic bile marker (indocyanine green). We studied 6 subjects with gallstones before and during administration of ursodeoxycholic acid (UDCA, 675 mg) at bedtime. Duplicate pretreatment studies revealed good reproducibility. Mean values for hepatic bile acid secretion rate were uninfluenced by chronic UDCA administration before the acute bedtime dose, but during the 4-h period after acute administration of UDCA the total bile acids secreted increased by a mean value of 2.2 mmol (p less than 0.01). Before treatment, nine of the 78 hourly samples were secreted at a hepatic bile acid secretion rate of less than 5 mumol/kg.h in the 6 patients studied, compared with only one hourly sample during UDCA administration. Super-saturated hepatic bile was secreted for a mean of 9.5 h before treatment, and for 1.2 h during UDCA treatment (p less than 0.005). We conclude that if UDCA is administered at bedtime, this maintains the hepatic bile acid secretion rate overnight, thus reducing secretion of supersaturated hepatic bile, in addition to the well-established effect of UDCA on cholesterol secretion.

Aged↗
PubMed1988

Hepatic handling of a synthetic gamma-labeled bile acid (75SeHCAT).

75Se-homocholic acid-taurine (75SeHCAT) is the first available gamma-labeled bile acid, and should therefore be handled more efficiently and specifically by the liver than previous hepatoscintigraphic agents. We have measured serum and hepatic kinetics for 75SeHCAT, and compared them with those for the conventional hepatobiliary scintigraphic agent 99mTc-hepatoiminodiacetic acid, and with serum kinetics for the corresponding natural bile acid, [14C]cholic acid-taurine. We used a dynamic scintigraphic technique and serial blood sampling in 8 subjects. Initial hepatic uptake rate was identical to initial serum disappearance rate (14% dose/min) for 75SeHCAT, but significantly lower for 99mTc-hepatoiminodiacetic acid (6% vs. 14% dose/min, p less than 0.001). Hepatic transit time was shorter for 75SeHCAT (13 min vs. 22 min, p less than 0.02), net hepatic excretory rate was more rapid (1.4% vs. 0.8% dose/min, p less than 0.001), and urinary excretion was lower (1.0% vs. 9.0% dose, p less than 0.001). Initial and late-plasma disappearance rates were significantly lower for 75SeHCAT (14.3% and 1.5% dose/min) than for [14C]cholic acid-taurine (21.3% and 2.8% dose/min, respectively), and plasma clearance was also lower (275 vs. 670 ml/min). In vitro, 75SeHCAT was bound to serum proteins more completely than [14C]cholic acid-taurine (90.4% vs. 86.5%, p less than 0.005). We conclude that 75SeHCAT provides a hepatoscintigraphic agent that is handled more efficiently and specifically by the liver than the conventionally used agent 99mTc-hepatoiminodiacetic acid. It is not cleared from the serum as rapidly as [14C]cholic acid-taurine, probably due to its stronger protein binding. The clinical value of 75SeHCAT in assessing liver disease should be investigated.

Adult↗
PubMed1988

Kinetics for the synthetic bile acid 75selenohomocholic acid-taurine in humans: comparison with [14C]taurocholate.

The "apparent" fractional turnover rate of the gamma-labeled bile acid analogue 75selenohomocholic acid-taurine (75SeHCAT) was assessed from decline in radioactivity over the gallbladder area on 4 successive days using a gamma-camera, and was compared in the same subjects with the fractional turnover rate of the corresponding natural bile acid, cholic acid-taurine, labeled with 14C ([14C]CAT) using the classical Lindstedt technique. Very similar results were obtained in 5 healthy individuals (coefficient of variation 4.8%, medians 0.35 and 0.34, respectively). By contrast, the fractional deconjugation rate assessed from zonal scanning of glycine- and taurine-conjugated bile acids on thin-layer chromatography was much less for 75SeHCAT than for [14C]CAT (0.02 and 0.13, respectively; p less than 0.05). The fractional rate for deconjugation plus dehydroxylation was also determined by zonal scanning, and gave lower values for 75SeHCAT than for [14C]CAT (0.02 and 0.12, respectively; p less than 0.05). There was a striking similarity between the fractional rate for deconjugation alone and that for deconjugation plus dehydroxylation for both bile acids in individual samples (r = 0.999, p less than 0.001), suggesting that these two processes might occur simultaneously and probably involve the same bacteria. We conclude that our scintiscanning technique provides an accurate, noninvasive method of measuring fractional turnover rate of a bile acid in humans, and that the finding that 75SeHCAT remains conjugated with taurine during enterohepatic recycling means that absorption should be specific for the ileal active transport site, thus rendering it an ideal substance for assessing ileal function.

Abdomen↗
PubMed1988

Effect of ursodeoxycholic acid on biliary lipid coupling and on cholesterol absorption during fasting and eating in subjects with cholesterol gallstones.

The aim of this study was to determine the effect of chronic ursodeoxycholic acid administration on coupling of bile acids with cholesterol and phospholipid in hepatic bile, and on cholesterol absorption in the duodenum. A range of bile acid secretion rates was obtained during an evening meal and an overnight fast. Duodenal perfusion of polyethylene glycol as a nonabsorbable recovery marker and of [3H]cholesterol and [14C]lecithin as absorbable recovery markers was combined with continuous intravenous infusion of indocyanine green as a hepatic bile marker. Six subjects with gallstones were studied before and during chronic administration of ursodeoxycholic acid (675 mg/day). Duplicate pretreatment studies revealed good reproducibility for biliary lipid coupling and cholesterol absorption. During ursodeoxycholic acid administration there was a significant alteration not only in bile acid/cholesterol coupling (p less than 0.001), but also in bile acid/phospholipid coupling (p less than 0.001). Mean cholesterol absorption decreased from 25% to 15% (p less than 0.001) during ursodeoxycholic acid administration. These effects of chronic ursodeoxycholic acid administration on biliary lipid coupling are similar to those reported for acute administration, and are thus consistent with an effect caused by bile acid lipid-solubilizing capacity.

Aged↗
PubMed1988

Increased risk of biliary tract cancer following gastric surgery.

Analysis of 4,466 peptic ulcer patients, who had undergone gastric surgery at least 25 years previously, showed no change in risk from biliary tract cancer within the first 20 years, but a 9.4 fold (P less than 0.001) excess risk thereafter. The increased risk was 15.8 fold (P less than 0.001) 20 years after operation for gastric ulcer patients and 5.1 fold (NS) in duodenal ulcer patients. When the risk was analysed by subsite it was found that there was no increased risk at any time after operation for cancer of the bile duct, and that all of the excess risk 20 or more years after operation (14.7 fold; P less than 0.001) was for cancer of the gallbladder.

Adult↗
PubMed1988

Enprostil, a prostaglandin E2 analogue, in the treatment of duodenal ulcer; a multicentre comparison with cimetidine.

In a multicentre trial, 120 patients with endoscopically diagnosed duodenal ulcer were randomly allocated to treatment with either 35 micrograms enprostil b.d. or 400 mg cimetidine b.d. for up to 6 weeks on a double-blind basis. After 6 weeks, 82% (42/51) of enprostil-treated patients and 92% (44/48) of cimetidine-treated patients were healed. Corresponding healing figures on an intention-to-treat basis were 70% and 76%. No significant differences were detected between treatments with respect to healing rates or symptom control at any time. Side-effects were reported by 14 patients taking enprostil and 17 patients taking cimetidine; none were serious but they resulted in withdrawal of one and two patients respectively. Enprostil was found to be similar in efficacy and tolerance to cimetidine.

Adolescent↗