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Biomedical subjects

T C Northfield

Publications and source records attributed to T C Northfield.

At least 127 records · Page 7Linked to original sources
PubMed1986

Ileal resection: effect of cimetidine and taurine on intrajejunal bile acid precipitation and lipid solubilisation.

We have investigated whether pH-dependent bile acid precipitation limits lipid solubilisation after ileal resection, and whether treatment with cimetidine, or taurine improves solubilisation. Nine ileal resection patients were treated with placebo, cimetidine and taurine in random order for two weeks each. Upper jejunal content was aspirated and pooled according to pH for three hours after a standard Lundh test meal. On placebo, 50% of the bile acids were precipitated at pH less than 5, compared with only 26% at pH greater than 6, whilst aqueous-phase lipid concentration tended to be lower at pH less than 5 than at pH greater than 6 (5.1 vs 8.2 mmol/l). On cimetidine mean pH rose, particularly during the third hour (6.6 vs 5.8, p less than 0.05), associated with a reduction in bile acid precipitation (13.9 vs 33.1%, p less than 0.05), and an increase in aqueous-phase lipid concentration (10.4 vs 6.6 mmol/l, p less than 0.05). On taurine, the proportion of taurine conjugated bile acids increased (67 vs 22%, p less than 0.01), but there was no significant change in bile acid precipitation or lipid solubilisation. Lower jejunal samples were aspirated similarly from five of these patients on no treatment, and all were at pH greater than 6; apparent 'precipitation' was reduced (16.4 vs 28.1%), but lipid solubilisation did not improve. These findings suggest that pH dependent bile acid precipitation can limit lipid solubilisation within the jejunum after ileal resection, and that these effects can be reduced by cimetidine but not by taurine. Cimetidine may have a role in ileal resection patients with severe steatorrhoea unresponsive to dietary fat restriction.

Adult↗
PubMed1986

Effects of a pharmacological dose of cholecystokinin on bile acid kinetics and biliary cholesterol saturation in man.

In order to study the mechanisms influencing bile acid pool size and cholesterol saturation index of fasting gall bladder bile, eight obese volunteers were placed on a low calorie diet for six weeks, and given intramuscular injections of a pharmacological dose of cholecystokinin octapeptide (CCK-OP, 5 micrograms) at mealtimes for half that period (alternating order). During CCK-OP administration, postprandial emptying of the gall bladder (mean +/- SEM) increased from 58 +/- 11% to 82 +/- 5% (p less than 0.005), and small intestinal transit time decreased from 205 +/- 27 to 178 +/- 26 minutes (NS). Bile acid pool size decreased from 4.6 +/- 0.3 to 3.1 +/- 0.3 mmol (p less than 0.001), while fractional turnover rate for chenodeoxycholic acid increased from 0.23 +/- 0.02 to 0.36 +/- 0.03 per day (p less than 0.005), suggesting an increase in recycling frequency of the pool. Synthesis rate was unchanged (0.43 +/- 0.08 vs 0.44 +/- 0.07 mmol/day), suggesting a new steady state. The cholesterol saturation index of fasting gall bladder bile increased in all subjects from 1.3 +/- 0.1 to 1.6 +/- 0.1 (p less than 0.005). Fasting gall bladder volume was reduced from 29 +/- 4 to 20 +/- 7 ml (p less than 0.01). Fractional turnover rate on the two regimens correlated with gall bladder emptying (n = 16, r = 0.61, p less than 0.01), but not with small intestinal transit time (r = 0.07, NS). Bile acid pool size correlated with fractional turnover rate (r = -0.73, p less than 0.005) and with cholesterol saturation index (r = -0.56, p less than 0.025). These findings suggest that CCK influences bile acid kinetics and cholesterol saturation index of fasting gall bladder in man; and that these effects of CCK are mainly mediated via alterations in gall bladder emptying rather than through alterations in small intestinal transit rate.

Adult↗
PubMed1986

Evaluation of the nitrosamine hypothesis of gastric carcinogenesis in precancerous conditions.

A 24 hour gastric aspiration study was carried out on nine Polya gastrectomy, eight pernicious anaemia, and nine matched control subjects. Intragastric pH, bacteria, nitrite, and N-nitroso compounds were assessed half hourly whilst ambulant and hourly when in bed. Both total and nitrate reducing bacterial counts were positively related to pH (chi 2 = 279.3; p less than 0.001), as was nitrite concentration (F = 19.1; p less than 0.0001). By contrast, total (F = 40.6; p less than 0.0001) and stable (F = 257.4; p less than 0.0001) N-nitroso compound concentrations were negatively related to pH. Clear differences in these gastric juice factors were not apparent between matched control and either pernicious anaemia, or Polya gastrectomy because the Polya gastrectomy and matched control groups were heterogeneous for gastric acidity. Thus, although eight of eight pernicious anaemia subjects were hypoacidic (defined as intragastric pH greater than 4 for greater than 50% of both daytime and night time periods), only five of nine Polya gastrectomy and two of nine matched control subjects were hypoacidic. When subjects were rearranged into hypoacidic (n = 15) and acidic (n = 11) groups, bacterial counts (p less than 0.01) and nitrite concentrations (p less than 0.01) were higher, whereas N-nitroso compounds tended to be lower (NS) in the hypoacidic group. These data suggest that, although hypoacidity predisposes to bacterial overgrowth and nitrite generation, it does not enhance nitrosation. Instead, this is maximal at low pH, suggesting chemical rather than bacterial nitrosation, contrary to the nitrosamine hypothesis of gastric carcinogenesis.

Aged↗
PubMed1986

Effects of artificial depletion of the bile acid pool in man.

In order to elucidate the relationship between bile acid pool size and cholesterol saturation index of fasting state gall bladder bile, we artificially depleted the bile acid pool in 12 healthy volunteers. Bile acid pool size decreased from 7.6 +/- 0.9 to 5.8 +/- 0.7 mmol (mean +/- SEM, p less than 0.01), and saturation index of fasting state gall bladder bile increased from 0.93 +/- 0.07 to 1.18 +/- 0.07 (p less than 0.001). There was no alteration in saturation index of basal or stimulated hepatic bile. There was no change in gall bladder storage of basal hepatic bile, nor in the proportion of the bile acid pool stored in the gall bladder. The bile acid mass in the gall bladder fell from 4.9 +/- 0.5 to 3.4 +/- 0.4 mmol (p less than 0.05) and phospholipid mass from 1.6 +/- 0.3 to 1.2 +/- 0.2 mmol (p less than 0.05), but there was no change in cholesterol mass. The gall bladder volume fell from 30 +/- 4 to 18 +/- 2 ml (p less than 0.01). These results suggest that artificial depletion of the bile acid pool increased saturation index of fasting state gall bladder bile without altering saturation index of basal or stimulated hepatic bile; it probably increased the ratio of basal: stimulated hepatic bile within the gall bladder by decreasing gall bladder storage of stimulated hepatic bile.

Adult↗
PubMed1985

Effect of cimetidine on enzyme inactivation, bile acid precipitation, and lipid solubilisation in pancreatic steatorrhoea due to cystic fibrosis.

In pancreatic steatorrhoea, both pH-dependent bile acid precipitation and enzyme inactivation may limit the efficacy of pancreatic enzyme supplements and both may be preventable by addition of cimetidine. To separate these effects we compared postprandial jejunal aspirate from eight adults with steatorrhoea due to cystic fibrosis on three randomised treatment regimens (pancreatin, cimetidine, and both together). We also compared the results with those of previous studies of patients on no treatment, and of healthy subjects. On pancreatin 60% of the test meal entered the jejunum at pH less than 5 compared with 17% in health. Lipase concentration and lipolysis increased over the values on no treatment (14.2 vs 4.4 U/l, p less than 0.01; 16% vs 11%, p less than 0.02) but bile acid precipitation was not reduced (38% vs 27%, NS), and aqueous-phase lipid concentration decreased (6.7 vs 8.6 mM/l, p less than 0.05). On cimetidine, bile acid precipitation fell (19% vs 38%, p less than 0.05); although lipase concentration and lipolysis were lower than on pancreatin (4.8 U/l vs 14.2 U/l, p less than 0.01; 9% vs 16%, p less than 0.01) lipid solubilisation increased (8.8 vs 6.7 mM/l, p less than 0.05). On the combination, there was a marked improvement (p less than 0.02) in lipid solubilisation (18.3 mM/l), reflecting the improvement both in lipase (38.4 U/l) and lipolysis (24%), and in bile acid precipitation (5.6%). We conclude that the efficacy of pancreatin is limited by pH-dependent bile acid precipitation in addition to enzyme inactivation. The action of cimetidine in improving the efficacy of pancreatin depends on prevention of both these effects.

Adolescent↗
PubMed1985

Quantification of temocillin biliary excretion and gallbladder bile concentration in healthy subjects.

The techniques of duodenal perfusion with polyethylene glycol as a nonabsorbable marker, and cholescintiscan using 99Tc HIDA as a gallbladder bile marker, were used to measure the total duodenal output and gallbladder bile concentration of temocillin after administration of an intravenous bolus injection to each of 6 healthy subjects. We carried out 8 studies. 3 with 0.5g temocillin and 5 with 1g temocillin. The plasma half-life of temocillin was 177 (+/- 25) minutes [mean (+/- SD)] and 196 (+/- 29) minutes with the 0.5g and 1g doses, respectively. Urinary excretion accounted for 38% of the total dose given during the study period of 6 hours, and total biliary excretion was recorded as 2.2% of the given dose for both doses. The mean concentration of temocillin in gallbladder bile was 314.7 (+/- 273.2) mg/L after the 0.5g dose and 474.5 (+/- 307.3) mg/L after 1g dose. It was concluded that temocillin is highly concentrated in the normal gallbladder in man.

Adult↗
PubMed1984

Which electrode? A comparison of four endoscopic methods of electrocoagulation in experimental bleeding ulcers.

Several inexpensive endoscopic methods of electrocoagulation have been advocated for treatment of gastrointestinal haemorrhage. We compared four types of electrode: dry monopolar - Cameron Miller (M), liquid monopolar - Storz (L), bipolar - Bicap ACMI (B), and heater probe - Seattle (H). The electrical and thermal properties of these probes were studied using computerised monitoring of energy deposition and their efficacy and safety was tested in a randomised study in 140 experimental canine gastric ulcers. At optimal pulse settings 20J (M), 70J (L), 17J (B), 15J (H), effective haemostasis was achieved in all ulcers, the mean number of pulses being M5, L6, H6 and B11, the first three requiring significantly (p less than 0.01) less pulse than B. Relative safety of the electrodes was assessed by comparing the incidence of full thickness damage at histology: B24%, H20%, L58% and M69%; B and H proving significantly (p less than 0.01) safer than L and M. Sticking was assessed as H greater than B greater than M much greater than L. Insensitivity to extreme angulation and force of application was assessed as L greater than B greater than M (H is preset). Of the two safer electrodes the heater probe was more effective than the bipolar probe. Despite its greater tendency to stick than the other devices, the heater probe appeared the most promising of the endoscopic electrodes tested.

Animals↗
PubMed1984

Effect of intrajejunal acidity on lipid digestion and aqueous solubilisation of bile acids and lipids in health, using a new simple method of lipase inactivation.

We have investigated whether acid-mediated bile acid precipitation, pancreatic enzyme inactivation, and fatty acid partitioning occur in health when intraluminal pH falls below 5. In order to assess lipolysis and aqueous solubilisation of lipid, we first developed a new technique for inactivating lipase in jejunal aspirate (acid inactivation), and showed it to be more effective and simpler than the established technique (heat inactivation). We then studied 14 healthy subjects, aspirating jejunal content for three hours after a liquid meal, and pooling according to pH. Eighteen per cent of the total aspirate was collected at pH less than 5 compared with 56% at pH greater than 6 (p less than 0.01). Forty eight per cent of the bile acids were precipitated at pH less than 5 compared with 18% at pH greater than 6 (p less than 0.01), leading to a reduction in aqueous phase bile acid concentration at low pH (2.1 mmol/l at pH less than 5 vs 5.8 mmol/l at pH greater than 6, p less than 0.01). Lipase activity was reduced at low pH (133 IU/l at pH less than 5 vs 182 IU/l at pH greater than 6, p less than 0.01), leading to reduced lipolysis at low pH (14% at pH less than 5 vs 32% at pH greater than 6, p less than 0.01). Aqueous phase lipid concentration was reduced at low pH (3.5 mmol/l at pH less than 5 vs 12.5 mmol/l at pH greater than 6, p less than 0.01). This reduction was less dependent on bile acid precipitation than on lipase inactivation and fatty acid partitioning. We conclude that intraluminal acidity influences aqueous solubilisation of bile acids and lipid in health.

Adult↗
PubMed1984

Effect of intrajejunal acidity on aqueous phase bile acid and lipid concentrations in pancreatic steatorrhoea due to cystic fibrosis.

We have investigated whether jejunal hyperacidity leads to bile acid precipitation and thus limits lipid solubilisation in patients with pancreatic steatorrhoea. Jejunal contents from 12 adults with steatorrhoea due to cystic fibrosis were aspirated for three hours after a liquid test meal, and pooled according to their pH. Thirty eight per cent of the total aspirate was collected at pH less than 5 in cystic fibrosis, compared with 18% in healthy controls (p less than 0.05). Forty six per cent of the bile acids were precipitated at pH less than 5, compared with 15% at pH greater than 6 (p less than 0.01), leading to reduced aqueous phase bile acid concentration at low pH (4.7 mmol/l at pH less than 5 vs 12.5 mmol/l at pH greater than 6, p less than 0.01). Aqueous phase lipid concentrations were reduced at low pH (5.6 mmol/l at pH less than 5 vs 10.2 mmol/l at pH greater than 6, p less than 0.01). Lipolysis and total fatty acid concentrations were greatly reduced and did not vary with pH. We therefore conclude that jejunal hyperacidity leads to bile acid precipitation in pancreatic steatorrhoea due to cystic fibrosis, and imposes a further limitation on lipid solubilisation over that of lipase deficiency.

Adult↗
PubMed1984

Comparative study of the safety and efficacy of liquid and dry monopolar electrocoagulation in experimental canine bleeding ulcers using computerized energy monitoring.

The drawbacks of monopolar electrocoagulation in the control of gastrointestinal bleeding include tissue adherence, unpredictable energy deposition, and a high incidence of tissue damage. Introduction of a conductive interfacial film of liquid between the monopolar electrode and the bleeding point during electrocoagulation may overcome these drawbacks. A prospective, controlled study was undertaken to evaluate the efficacy and safety of a monopolar electrode in liquid and dry modes when used to coagulate experimental canine bleeding ulcers. All experiments were done in open fashion via a gastrotomy with hand-held electrodes. An analog computer, which could be connected between a standard electrosurgical generator and the electrode, was designed and built to monitor and control the energy delivered to the tissue. Both liquid and dry electrodes were highly effective in stopping bleeding. The liquid electrode was found to be superior to the dry electrode in that tissue adherence was eliminated and energy deposition was more predictable, varying less with angle of incidence. The liquid electrode caused less macroscopic serosal damage and less full-thickness histologic damage if the total energy or number of pulses was limited; however, both caused microscopic full-thickness damage in one-half of the experimental ulcers treated, although no perforations occurred.

Animals↗
PubMed1983

Five years' experience of a gastroenterology day-case unit.

An inpatient ward has been converted, at low cost, to a gastroenterology day-case unit, which includes a purpose-built endoscopy room and a day-case area. The presence of a day-case ward permits the nursing establishment to be sufficiently flexible to cover the endoscopy room fully, and the hours are suitable for married nurses with families. Patients remain on the same trolley throughout the procedure so that portering delays are avoided, and a good flow system operated by the unit's staff enables endoscopies to be carried out at the rate of one every ten to fifteen minutes. Admissions rose from 1900 to 2700 per year (an average of 12 X 5 admissions per working day, theoretical bed occupancy = 140%). Cost per patient is about half the estimated cost without a day-case unit. The increasing numbers of routine upper gastrointestinal endoscopies are mirrored by a halving of barium-meal examinations.

Bed Conversion↗
PubMed1983

Effect of sodium acetyl salicylate on cholesterol saturation of fasting gall bladder bile, with and without chenic acid.

The aims of this study were (a) to determine whether sodium acetyl salicylate by itself or in combination with chenodeoxycholic (chenic) acid would decrease the cholesterol saturation index (SI) of fasting gall bladder bile in man; and (b) to confirm prospectively that 8 mg kg-1 day-1 chenic acid given at bedtime together with a low cholesterol diet reduces gall bladder bile SI to a level where consistent gallstone dissolution would be expected. Seven patients were studied on each of the following regimens given in random order for 1 month each: bedtime chenic acid alone 8 mg kg-1 day-1; sodium acetyl salicylate alone 600 mg four times daily; bedtime chenic acid together with sodium acetyl salicylate; no treatment. Gall bladder samples were taken by nasoduodenal intubation at the end of each regimen and SI determined. SI (mean +/- s.e. mean) on low cholesterol diet with no drug treatment was 1.14 +/- 0.06. On bedtime chenic acid 8 mg kg-1 day-1 plus low cholesterol diet it fell to 0.83 +/- 0.03 (P less than 0.05). Sodium acetyl salicylate did not alter gall bladder bile SI. 95% confidence limits for the effect of sodium acetyl salicylate on SI were +0.03 and -0.05. We conclude that (a) sodium acetyl salicylate does not lower SI of gall bladder bile in man; (b) an adequate fall in SI for gallstone dissolution can be achieved with a reduced dose (8 mg kg-1 day-1) of chenic acid given at bedtime with a low cholesterol diet.

Aged↗
PubMed1983

Factors affecting gall-stone dissolution rate during chenic acid therapy.

Gall-stone dissolution rate was measured in 52 patients with radiolucent gall stones in a functioning gall bladder receiving chenic acid 15 mg/kg/day. Percentage reduction in gall-stone area at six months was inversely related to initial gall-stone diameter (n = 52; r = -0.53; p less than 0.001), and to cholesterol saturation index of fasting gall-bladder bile during treatment (n = 28; r = -0.61; p less than 0.001). The duration of treatment required for complete dissolution was directly related to initial gall-stone diameter (r = 0.47; p less than 0.02). We conclude that the rate of gall-stone dissolution depends not only on gall-stone size but also on the degree of unsaturation of gall-bladder bile achieved during chenic acid treatment.

Adolescent↗
PubMed1983

Diurnal variation in cholesterol saturation of gall-bladder bile.

In order to determine whether a diurnal variation in cholesterol saturation index is present in gall-bladder bile, samples of bile were taken by nasoduodenal intubation and cholecystokinin infusion at 9 am after the conventional 12 hour fast, and also at 5 pm five hours after a meal containing no cholesterol or phospholipid. In healthy controls saturation index (mean +/- SEM) fell from 1.02 +/- 0.08 at 9 am to 0.86 +/- 0.08 at 5 pm (n = 8, p less than 0.05). In untreated cholesterol gall-stone patients saturation index fell from 1.30 +/- 0.07 to 1.04 +/- 0.07 (n = 8, p less than 0.05); on chenodeoxycholic acid 15 mg/kg/day it fell from 0.91 +/- 0.06 to 0.78 +/- 0.07 (n = 16, p less than 0.01). The degree of diurnal variation was similar in those taking chenodeoxycholic acid at bedtime and in those taking it at mealtimes. The 9 am sample was supersaturated in three non-responders (showing no evidence of gall stone dissolution on oral cholecystogram after at least six months treatment) and in four responders. The 5 pm sample was a better predictor of treatment failure, being supersaturated in all four non-responders but in only one out of the 12 responders (p less than 0.01).

Adult↗
PubMed1982

Duodenal intubation as a source of typhoid fever.

Typhoid fever developed in three patients during a period of 13 weeks. Although each of these patients was admitted to a different London hospital, the patients became ill approximately 10 days after undergoing duodenal intubation in one gastroenterology unit. All other patients who had undergone duodenal intubation in the unit during that period of time were investigated. Salmonella typhi was isolated from bile and feces of two out of the 20 other patients (carriers). In each of the three patients who developed typhoid fever, intubation followed within two days of intubation of one of the carriers. After use in each patient, the polyvinyl tubes had been thoroughly washed with disinfectant and detergent. There were no further cases of typhoid fever when a new tube was used for each patient.

Adolescent↗