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Biomedical subjects

T C Northfield

Publications and source records attributed to T C Northfield.

At least 19 recordsLinked to original sources
PubMed1992

Childhood living conditions and Helicobacter pylori seropositivity in adult life.

Infection with Helicobacter pylori increases an individual's risk of peptic ulceration and gastric cancer. In the developed world, prevalence of infection rises with age and varies with social class. We used a cross-sectional study design to test the hypothesis that H pylori infection would be more closely associated with childhood living conditions than with current socioeconomic status. Prevalence of IgG antibodies against H pylori was determined with an enzyme-linked immunosorbent assay in 215 subjects (median age 46 years, range 18-82) attending a health-screening clinic in London. Seropositivity varied from 9% (age less than 30) to 67% (greater than or equal to 70). Subjects were asked about their living conditions at present and when they were aged 8 years. Absence of a fixed hot-water supply (p = 0.0005) and domestic crowding (p = 0.0005) in childhood were powerful independent risk factors for current infection with H pylori. Among current living conditions, only the number of children living in the household was independently associated with H pylori infection (p = 0.004). Most British adults infected with H pylori probably became infected by household contact in childhood.

Adult↗
PubMed1992

Surface hydrophobicity of gastric mucosa in Helicobacter pylori infection: effect of clearance and eradication.

Surface hydrophobicity of the gastric mucosa is reduced in peptic ulcer disease and Helicobacter pylori infection. This abnormality may be caused by H. pylori or may be an inherent defect. The aim of the present study was to clarify the relationship between H. pylori infection and mucosal hydrophobicity by examining the effect of eradication of the organism. H. pylori-positive patients with (n = 42) or without (n = 42) duodenal ulcer were randomized to receive ranitidine, bismuth, or bismuth plus antibiotics. Surface hydrophobicity of gastric mucosa was assessed by measurement of plateau-advancing contact angle. Measurements were performed at presentation, end of treatment, and 1 month later. Contact angle was unchanged after ranitidine (55 degrees vs. 56 degrees) but increased with bismuth (57 degrees-62 degrees; P < 0.05) and bismuth plus antibiotics (56 degrees-67 degrees; P < 0.0001). One month after treatment ended, contact angles in patients in whom H. pylori was not eradicated were not different from those before treatment (56 degrees vs. 56 degrees) but increased to a value similar to H. pylori-negative controls in patients in whom H. pylori was eradicated (56 degrees-69 degrees; P < 0.0001). It is concluded that reduced mucosal hydrophobicity in peptic ulcer disease is secondary to H. pylori infection and that this impaired mucosal defense provides a possible mechanism whereby H. pylori infection predisposes to acid/peptic digestion.

Adult↗
PubMed1992

Management of recurrent gallstones.

The risk of gallstone recurrence following non-surgical treatment has been overestimated in the past for two reasons: (1) diagnosis of primary gallstone dissolution was based on oral cholecystography; and (2) gallstone recurrence was expressed as a cumulative recurrence rate. Results based on better methodologies for diagnosis of gallstones (ultrasonography) and for calculation of results (life-table analysis) have indicated that gallstones recur in about 50% of patients, and that the risk of recurrence is confined mainly to the first 5 years after dissolution. Pretreatment gallstone characteristics, but not patient characteristics, are important risk factors for gallstone recurrence. Multiple stones are more likely to recur than solitary stones, a phenomenon attributable to the presence of a potent pronucleating factor in the bile of patients with multiple stones. This observation, and the finding that NSAID administration may reduce gallstone recurrence via inhibition of mucin secretion, suggests that the nucleation defect might be a key factor in the pathogenesis of recurrent gallstones. Prophylaxis with low-dose CDCA or UDCA has proven ineffective for preventing gallstone recurrence, although it may reduce it. Since the majority of recurrent gallstones are small when first seen because of regular ultrasonographic follow-up, multiple, radiolucent and in functioning gallbladders, they are amenable to bile acid retreatment, and intermittent bile acid therapy is probably a viable strategy for long-term management of cholesterol cholelithiasis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Increased intragastric acid-resistant lipase activity and lipolysis in pancreatic steatorrhoea due to cystic fibrosis.

We measured gastric lipase activity and lipolysis in postprandial gastric samples from 10 adults with steatorrhoea due to cystic fibrosis (CF) and from 10 healthy volunteers of similar age and sex. Gastric samples were aspirated for 2 h following a meal consisting of emulsified long-chain triglyceride. Mean acid-resistant lipase activity was twice as high in CF patients as in controls (596 vs. 299 nmol/ml/min fatty acid released; p = 0.028 for area under the curve). Lipolysis rose from 5 to 10% during the postprandial period in CF patients, compared with a constant 5% in controls (p = 0.036 for area under the curve). We conclude that, in healthy adults, lipolysis of long-chain triglyceride starts in the stomach, while in adults with pancreatic steatorrhoea due to CF, gastric lipase activity and intragastric lipolysis are increased, perhaps in compensation for pancreatic insufficiency.

Adult↗
PubMed1992

Therapeutic potential and clinical efficacy of acid-resistant fungal lipase in the treatment of pancreatic steatorrhoea due to cystic fibrosis.

We investigated the therapeutic potential of an acid-resistant fungal lipase prepared from Aspergillus niger. We first demonstrated in vitro that it had a wide pH optimum of 2.5-5.5 and was resistant to pepsin and trypsin. We gave the enzyme or matching placebo in random order by mouth with a fatty meal to 10 adult patients with pancreatic steatorrhoea due to cystic fibrosis (CF) and sampled gastric contents for the following 2 h. Mean acid-resistant lipase activity was 330 nmol/ml/min free fatty acid released on placebo, compared with 896 nmol/ml/min on fungal lipase (p = 0.006 for area under the curve). We compared this lipase's clinical efficacy with that of two conventional pancreatin microsphere formulations in an open randomised crossover fat-balance study in 10 similar patients. Each preparation was given for 2 weeks, and a fat-balance study, using a faecal recovery marker, was performed on the final 3 days; a period without treatment was also included. The fungal lipase had no effect on faecal wet weight or on the coefficient of fat absorption (59.0% vs. 52.3%; NS) in comparison with placebo. The established enteric-coated microsphere preparation (Creon) produced a significant reduction in faecal wet weight and improvement in coefficient of fat absorption (81.4% vs. 52.3%; p less than 0.01) in comparison with placebo. The newer microsphere preparation (Pancrex M) was also effective, but perhaps less so than Creon; there were no significant differences between the two preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acids↗
PubMed1992

Optimum bile acid treatment for rapid gall stone dissolution.

To determine the optimum bile acid regimen for rapid gall stone dissolution, 48 gall stone patients were divided into four groups of 12 according to stone diameter and were randomly allocated to receive one of four treatment regimens: bedtime or mealtime chenodeoxycholic acid (CDCA, 12 mg/kg/day) and bedtime or mealtime ursodeoxycholic acid (UDCA, 12 mg/kg/day). An additional 10 patients treated with a combination of CDCA plus UDCA (each 6 mg/kg/day) at bedtime were matched with the 10 patients on bedtime CDCA and the 10 on bedtime UDCA. The gall stone dissolution rates at six and 12 months were determined by standardised oral cholecystography and expressed as the percentage reduction in the gall stone volume after treatment. The gall stone dissolution rate at six months was higher for UDCA than CDCA treatment (median 78% v 48%, p less than 0.01), and for bedtime than mealtime administration (69% v 39%, p less than 0.02). Both differences were greater for stones less than 8 mm diameter. The dissolution rate was faster for combination therapy than for CDCA alone at both six (82% v 36%, p less than 0.05) and 12 months (100% v 54%, p less than 0.05), but was not different from UDCA alone. We conclude that bile acid treatment should be confined to patients with small gall stones and that bedtime administration of combined UDCA and CDCA is likely to provide the most effective and safe combination.

Chenodeoxycholic Acid↗
PubMed1991

Direct measurement of first-pass ileal clearance of a bile acid in humans.

The purpose of this study was to develop and validate a method of directly measuring ileal bile acid absorption efficiency during a single enterohepatic cycle (first-pass ileal clearance). This has become feasible for the first time because of the availability of the synthetic gamma-labeled bile acid 75Selena-homocholic acid-taurine (75SeHCAT). Together with the corresponding natural bile acid cholic acid-taurine (labeled with 14C), SeHCAT was infused distal to an occluding balloon situated beyond the ampulla of Vater in six healthy subjects. Completion of a single enterohepatic cycle was assessed by obtaining a plateau for 75SeHCAT activity proximal to the occluding balloon, which prevented further cycles. Unabsorbed 75SeHCAT was collected after total gut washout, which was administered distal to the occluding balloon. 75SeHCAT activity in the rectal effluent measured by gamma counter was compared with that of absorbed 75SeHCAT level measured by gamma camera and was used to calculate first-pass ileal clearance. This was very efficient (mean value, 96%) and showed very little variation in the six subjects studied (range, 95%-97%). A parallel time-activity course in hepatic bile for 14C and 75Se during a single enterohepatic cycle, together with a ratio of unity for 14C/75Se in samples obtained at different time intervals, suggests that 75SeHCAT is handled by the ileum like the natural bile acid cholic acid-taurine. Extrapolation of 75SeHCAT first-pass ileal clearance to that of the natural bile acid therefore seems justifiable. In a subsidiary experiment, ileal absorption efficiency per day for 75SeHCAT was also measured by scanning the gallbladder area on 5 successive days after the measurement of first-pass ileal clearance. In contrast with absorption efficiency per cycle, absorption efficiency per day varied widely (49%-86%), implying a possible wide variation in recycling frequency per day.

Adult↗
PubMed1991

Ursodeoxycholic acid in chronic liver disease.

The hydrophilic bile acid ursodeoxycholic acid has recently been shown to reduce biochemical markers of both cholestasis and hepatocellular damage in patients with chronic liver diseases. The most compelling evidence available is for chronic cholestatic liver diseases, in particular primary biliary cirrhosis, primary sclerosing cholangitis, and cholestasis associated with cystic fibrosis. The effects may be less beneficial in patients with advanced liver disease from these conditions. Data from placebo controlled trials are now available in support of earlier uncontrolled observations, but it is not yet clear whether short term benefit results in an improvement in longterm prognosis. The mechanism of action of the compound seems to reside in its displacement of toxic hydrophobic bile acids from both the bile acid pool and hepatocellular membranes. There may be an independent effect on bile flow, which could be of particular importance in cystic fibrosis, and possibly an effect on the immune system. Ursodeoxycholic acid should now be regarded as occupying a central place in the medical management of chronic cholestatic liver diseases, in particular primary biliary cirrhosis, because it improves cholestasis and reduces hepatocellular damage and it is not toxic. Research should now be targeted on whether treatment with ursodeoxycholic acid, initiated early in cholestatic liver conditions, improves the long-term outcome.

Animals↗
PubMed1991

A practical guide to the nonsurgical treatment of gallstones.

Until recently, cholecystectomy was the only treatment available for symptomatic gallstone disease. During the past 20 years, better understanding of the pathogenesis of cholesterol gallstone disease has led to alternative nonsurgical methods for treating gallstones in selected groups of patients. Use of 2 naturally occurring bile acids, chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), was reported in 1972 and 1975, respectively, for successful dissolution of cholesterol gallstones in humans. Both these bile acids act by reducing cholesterol secretion in bile, thus enabling it to solubilise more cholesterol from the stone surface. Micellar solubilisation is involved, together with liquid crystal formation in the case of UDCA. Having been extensively studied in clinical trials to assess efficacy and safety, both these compounds are now available for general use. The efficacy of CDCA can be enhanced by single bedtime dose administration and by taking a low cholesterol diet. Bedtime administration also enhances the effect of a suboptimal dose of UDCA. CDCA induces dose-related diarrhoea and hypertransaminaemia, and UDCA can induce calcification of gallstones, thus rendering them resistant to medical dissolution. A combination of the 2 bile acids at half the recommended dose for each has become an accepted practice for reducing adverse effects, and this may also enhance efficacy. One of the main problems of bile acid therapy is that dissolution of gallstones is a very slow process. Use of extracorporeal shockwave lithotripsy (ESWL) to break the stones into smaller fragments, with concurrent use of bile acids, has been shown to speed dissolution rate and to achieve complete gallstone dissolution in 78% of selected cases within 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Chenodeoxycholic Acid↗
PubMed1991

Factors affecting gastric mucosal hydrophobicity in man.

Contact angle measurements in animal studies have demonstrated that gastric mucosa has a relatively hydrophobic surface. We have developed and validated a technique for the measurement of this property on human endoscopic biopsy specimens. Mean contact angle of the gastric body (70 degrees) and antrum (70 degrees) was higher than the duodenal bulb (62 degrees; p less than 0.01) and distal duodenum (50 degrees; p less than 0.001). Subjects with duodenal ulcer and gastric ulcer had a lower contact angle than controls without ulcer (57 degrees, n = 49, and 59 degrees, n = 17 versus 66 degrees, n = 124, respectively). Helicobacter pylori infection was associated with reduced contact angle in subjects with gastritis (59 degrees versus 68 degrees). The contact angle was unchanged after treatment with ranitidine but increased to control values after clearance and eradication of H. pylori with bismuth and antibiotics. In postgastrectomy patients, the contact angle was reduced and correlated negatively with the bile acid content of gastric juice (r = 0.51, p less than 0.0001). We conclude that in man gastric mucosal hydrophobicity can be validly measured on endoscopic biopsy specimens and that it is high in health and reduced in bile reflux and in peptic ulcer disease, largely as a result of H. pylori infection.

Bile Reflux↗
PubMed1990

Relation between severity and extent of precancerous lesions in the postoperative stomach.

The relation between the severity and extent of precancerous lesions in a precancerous condition of the stomach was assessed, to find a means of reducing the endoscopic workload required for the detection of such lesions. 87 subjects who had had gastric surgery for peptic ulcer more than 20 years ago underwent gastric endoscopy and biopsy. Severity of dysplasia correlated with its extent. Severity of intestinal metaplasia correlated with its extent and with severity of dysplasia. Type of operation, but not sex or type of ulcer, was the factor most strongly associated with dysplasia. Previous Billroth II operations were more strongly associated with occurrence of dysplasia (85%) than were other operations. In patients with previous Billroth II operations, moderate and severe dysplasia were commoner around the stoma (37%) than in the body (10%). These findings indicate that there is a relation between the severity and extent of precancerous lesions, which suggests that patients with dysplasia have widespread gastric mucosal instability. They also indicate that, if endoscopic screening is limited to Bilroth II subjects and if biopsies are limited to the stoma, endoscopic workload can be reduced by 85%, with only a small reduction (15%) in detection of moderate and severe dysplasia.

Biopsy↗
PubMed1990

Randomized comparison of Nd YAG laser, heater probe, and no endoscopic therapy for bleeding peptic ulcers.

Of 550 patients admitted with acute upper gastrointestinal hemorrhage, 143 with peptic ulcers containing stigmata of recent hemorrhage accessible to endoscopic therapy were included in a randomized comparison of neodymium yttrium aluminum garnet laser, heater probe, and no endoscopic therapy. The rebleeding rate in laser-treated patients (20%) was significantly less than in controls (42%; p less than 0.05), but in heater probe-treated patients (28%) it was not significantly different from either of the other two groups. The mortality rate in the laser group (2%) was not significantly different from either the heater probe (10%) or the control (9%) group. This trial has confirmed the efficacy of the Nd YAG laser but not that of the heater probe in the prevention of rebleeding from recently bleeding peptic ulcers.

Duodenal Ulcer↗
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

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

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↗