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Biomedical subjects

T C Northfield

Publications and source records attributed to T C Northfield.

At least 109 records · Page 6Linked to original sources
PubMed1988

Low power interstitial Nd YAG laser photocoagulation in normal and neoplastic rat colon.

The effects of low power (1-2 Watts), long exposure (30-400 seconds), interstitial Nd YAG laser therapy on dimethylhydrazine induced rat colonic neoplasms and normal rat colon have been studied. After a single exposure with appropriate laser parameters, dimethylhydrazine induced rat colonic neoplasms underwent coagulative necrosis, sloughed off over a four day period, and left an ulcer which healed within 28 days. Inadequate laser energy resulted in incomplete tumour necrosis whilst excessive laser power or energy increased the likelihood of perforation. Treatment of normal colon with 1 Watt for 30 seconds or longer resulted in coagulative damage which healed by granulation. Mean colonic bursting pressures were significantly decreased one hour after treatment with 1 Watt for 75 or 100 seconds compared with untreated colon (p less than 0.05 and p less than 0.001 respectively) but not in colon treated with 1 Watt for 30 or 50 seconds. In animals treated with 1 Watt for 100 seconds mean bursting pressures were significantly lower than untreated animals when the animals were killed two, four, and seven days after lasering (p less than 0.001 in each case) but not in animals killed at 11, 17, or 21 days. The technique may be of value in the treatment of some inoperable colorectal cancers and sessile polyps in man.

Animals↗
PubMed1988

Which peptic ulcer patients bleed?

In order to identify factors associated with peptic ulcers which present with bleeding rather than with pain, we have prospectively evaluated patient and endoscopic features in 139 consecutive patients presenting with acute bleeding and 74 presenting with pain found to have peptic ulceration at endoscopy. Patients with bleeding were more likely to have taken non-steroidal anti-inflammatory drugs within the preceding four weeks (58% v 18%, p less than 0.001). They were older (66 v 51 years, p less than 0.001), more likely to have had a previous ulcer complication (21% v 1%, p less than 0.001), and to have an ulcer diameter greater than 20 mm (27% v 6%, p less than 0.05). The presence of one or more of these features in a patient who develops a peptic ulcer appears to be associated with a greater likelihood of presentation with a gastrointestinal haemorrhage.

Adult↗
PubMed1987

Solubilization of lipids from hamster bile-canalicular and contiguous membranes and from human erythrocyte membranes by conjugated bile salts.

We have demonstrated in vitro the efficacy of the taurine-conjugated dihydroxy bile salts deoxycholate and chenodeoxycholate in solubilizing both cholesterol and phospholipid from hamster liver bile-canalicular and contiguous membranes and from human erythrocyte membrane. On the other hand, the dihydroxy bile salt ursodeoxycholate and the trihydroxy bile salt cholate solubilize much less lipid. The lipid solubilization by the four bile salts correlated well with their hydrophobicity: glycochenodeoxycolate, which is more hydrophobic than the tauro derivative, also solubilized more lipid. All the dihydroxy bile salts have a threshold concentration above which lipid solubilization increases rapidly; this correlates approximately with the critical micellar concentration. The non-micelle-forming bile salt dehydrocholate solubilized no lipid at all up to 32 mM. All the dihydroxy bile acids are much more efficient at solubilizing phospholipid than cholesterol. Cholate does not show such a pronounced discrimination. Lipid solubilization by chenodeoxycholate was essentially complete within 1 min, whereas that by cholate was linear up to 5 min. Maximal lipid solubilization with chenodeoxycholate occurred at 8-12 mM; solubilization by cholate was linear up to 32 mM. Ursodeoxycholate was the only dihydroxy bile salt which was able to solubilize phospholipid (although not cholesterol) below the critical micellar concentration. This similarity between cholate and ursodeoxycholate may reflect their ability to form a more extensive liquid-crystal system. Membrane specificity was demonstrated only inasmuch as the lower the cholesterol/phospholipid ratio in the membrane, the greater the fractional solubilization of cholesterol by bile salts, i.e. the total amount of cholesterol solubilized depended only on the bile-salt concentration. On the other hand, the total amount of phospholipid solubilized decreased with increasing cholesterol/phospholipid ratio in the membrane.

Animals↗
PubMed1987

Biological effects of intrahepatic neodymium:yttrium-aluminum-garnet laser photocoagulation in rats.

The effects of low-power neodymium:yttrium-aluminum-garnet laser light delivered intrahepatically in normal rats have been studied. Power settings of 0.5-2.0 W and exposures of 50-2400 s produced well-defined, highly reproducible necrotic lesions of up to 16 mm in diameter. The diameter of the necrotic lesions depended upon both the power setting and total energy delivered. Histologic examination showed coagulative necrosis that healed by granulation with a small residual fibrous nodule by 60 days. Microthermocouples embedded within the liver indicated temperatures of up to 100 degrees C close to the fiber tip for the higher power settings, and temperatures at the periphery of the necrotic zones were consistent with tissue damage by a purely thermal effect. Radiologic examination of photocoagulated lobes of liver in which arterial tree had been filled with a radiopaque polymer demonstrated loss of all small and some large vessels in the treated area. The technique could be used to induce necrosis of intrahepatic and other tumors.

Aluminum↗
PubMed1987

Simultaneous quantitative measurements of absolute gallbladder storage and emptying during fasting and eating in humans.

We have carried out simultaneous, quantitative measurements of absolute gallbladder (GB) storage and emptying in 6 subjects with gallstones, using a modified duodenal perfusion technique that incorporates technetium 99m-labeled diethyl phenylcarbamomethyl iminodiacetate (99mTc-HIDA) as a GB bile marker in addition to indocyanine green as a hepatic bile marker. The technique was validated by measuring duodenal recovery of 99mTc-HIDA (mean +/- SEM, 101% +/- 4%), and also by studying 2 subjects who had undergone cholecystectomy. During the first hour following an evening meal, cumulative GB ejection of 99mTc-HIDA in the 6 subjects with gallstones was 43% +/- 12%. This was accompanied by GB storage of most hepatic indocyanine green (70% +/- 5%) during each 10-min interval of that hour. During subsequent overnight fasting, storage of hepatic indocyanine green (89% +/- 2%) was accompanied by ejection of 99mTc-HIDA from the GB in 33 of the 66 hourly intervals. Since 'simultaneous' filling and emptying cannot occur through the cystic duct, the results suggest frequent alternations in absolute GB storage and emptying, a phenomenon more analogous to a bellows than to the conventional concept of a simple pump.

Aged↗
PubMed1987

Bile acid binding to dietary casein: a study in vitro and in vivo.

1. Studies were carried out in vitro using an ultracentrifugation method to quantify bile acid binding to the different components of a Lundh test meal, and to determine what factors influence bile acid binding to one of the components (casein). We validated the ultracentrifugation method by showing good agreement with the equilibrium dialysis method. Studies were carried out in vivo on jejunal aspirate from 10 ileal resection patients in order to determine whether bile acid binding to casein could be demonstrated, and whether this influenced aqueous-phase bile acid and fatty acid concentrations. 2. In vitro, the Lundh test meal was found to adsorb bile acid. The protein content of the meal (casein) alone accounted for this binding, which was abolished by use of casein hydrolysate. The binding to casein was a saturable process. Both binding affinity and binding capacity were significantly greater for taurocholate at pH 4.5 than at pH 6.5, and for dihydroxylated than for trihydroxylated bile acid, suggesting that hydrophobic bonding was involved. 3. In vivo, jejunal samples aspirated at pH greater than 6 from 10 ileal resection patients showed 25% binding of bile acid to protein. On substitution of amino acids for casein, mean binding was reduced to 16% (P less than 0.05), residual binding being attributed to endogenous protein. This was associated with an increase in fatty acid solubilization from 28% to 60% (P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Review: pancreatic enzyme replacement--applied physiology and pharmacology.

The treatment of pancreatic steatorrhoea can often be improved by attention to the pathophysiological and pharmacological principles involved. Factors influencing the efficacy of pancreatic enzyme replacement include physiological characteristics of the individual patient and pharmaceutical characteristics of the supplement. Different patients may be best suited by different preparations and there is no overall 'best buy'. The new enteric-coated microsphere formulations are often most effective, but also more expensive than conventional preparations. Adjunctive H2-blockade can help appropriately selected patients with resistant steatorrhoea. Knowledge of the underlying cause may guide the choice of supplement and its dose, but trials of different regimens may prove necessary. Successful management, particularly of malnourished patients, involves optimization of dietary fat intake in addition to enzyme replacement.

Humans↗
PubMed1987

Urinary N-nitrosoproline excretion: a further evaluation of the nitrosamine hypothesis of gastric carcinogenesis in precancerous conditions.

Measurement of N-nitroso compounds in gastric juice by different methods has given conflicting results. In order to resolve this controversy, we have assessed endogenous nitrosation by the independent N-nitrosoproline excretion test in subjects who had previously undergone gastric juice analysis by one of these methods. Ten Polya gastrectomy, 10 pernicious anaemia and nine matched control subjects were fed 380 mg of nitrate in beetroot juice and 500 mg proline. N-nitrosoproline (N-Pro) synthesised intragastrically from these precursors, and quantitatively excreted by the kidneys, was measured in 24 hour urine samples (collection checked by creatinine clearance). N-Pro excretion (mean +/- SEM) was reduced (p less than 0.01) in pernicious anaemia (1.1 +/- 0.8 ng/day) compared with matched control (18.0 +/- 7.2 ng/day), and also tended to be lower (NS) in polya gastrectomy (3.2 +/- 2.3 ng/day). Twenty four hour intragastric pH was monitored on a separate occasion in 23 of the 29 subjects; 13 were hypoacidic (pH greater than 4 greater than 50% of 24 hours) and 10 were acidic. N-Pro yields were reduced (p less than 0.01) in the hypoacidic group (0.9 +/- 0.6 ng/day) compared with the acidic group (17.9 +/- 6.6 ng/day), and N-Pro was negatively associated with mean intragastric pH (tau = -0.53, p = 0.001). We conclude that endogenous synthesis of this specific N-nitroso compound is favoured by low rather than high pH. These results are concordant with those previously reported in gastric juice from the same subjects and suggest that nitrosation is chemically rather than bacterially mediated, contrary to the nitrosamine hypothesis of gastric carcinogenesis.

Aged↗
PubMed1987

Effect of bedtime ranitidine on overnight gastric acid output and intragastric pH: dose/response study and comparison with cimetidine.

A dose/response study has been carried out in seven patients with endoscopically proven duodenal ulcers in symptomatic remission, measuring intragastric pH and gastric acid output overnight after a bedtime dose of ranitidine (75 mg, 150 mg, and 300 mg); and the results have been compared with placebo and with bedtime cimetidine 400 mg. The currently recommended ranitidine maintenance dose (150 mg) was the optimum because it was significantly more effective than ranitidine 75 mg in terms of intragastric pH but not of acid output, and there was no difference from 300 mg in terms of either measurement. It was also significantly more effective than the currently recommended cimetidine maintenance dose (400 mg) in terms of inhibiting overnight acid output (92% vs 80% inhibition, p less than 0.05), and of maintaining intragastric pH above 5 (100% vs 17% of the overnight period, p less than 0.001).

Adult↗
PubMed1987

Increased risk of cancer at multiple sites after gastric surgery for peptic ulcer.

Of 5018 patients who had undergone gastric surgery at St James Hospital, Balham, at least 25 years ago, death certificates have been received for 2768, whilst 1746 patients are still alive and are flagged (Office of Populations, Censuses and Surveys (OPCS) will notify us of their death and its cause) and only 504 could not be traced. Mortality from cancers of various organs has been determined using a 'years at risk' calculation in five year bands. There was no increase in mortality risk from any cancers during the first 15 postoperative years, but from 20 years after operation there was a significant excess risk not only of cancer of the stomach (4.5-fold), but also of the large bowel (1.6-fold), bronchus (3.9-fold), pancreas (4.0-fold), biliary tract (9.1-fold), oesophagus (2.3-fold), bladder (2.4-fold), breast (4.0-fold), and cancer of all sites (3.3-fold). These findings are consistent with the production in the operated-upon stomach of circulating carcinogens with a 20 year latency period.

Humans↗
PubMed1987

Evaluation of the nitrosamine hypothesis of gastric carcinogenesis in man.

Patients who had undergone a Billroth II gastrectomy (PG) or had pernicious anaemia (PA) and healthy matched control subjects (MC) participated in 24-h studies in which bacteria, nitrite and N-nitroso compounds (NOC) were measured in gastric juice and N-nitrosoproline (NPRO) in urine. Consistent with the nitrosamine hypothesis, intragastric levels of bacteria and nitrite were positively related to intragastric pH, but, contrary to the hypothesis, NOC in gastric juice and NPRO in urine were negatively related to intragastric pH.

Anemia, Pernicious↗
PubMed1986

Controlled trial of Nd-YAG laser photocoagulation in bleeding peptic ulcers.

The efficacy of Nd-YAG laser photocoagulation in the endoscopic control of haemorrhage from peptic ulcers was shown in a controlled trial. 527 patients admitted consecutively with acute upper gastrointestinal haemorrhage underwent urgent endoscopy. Peptic ulcers were seen in 260. All 138 ulcer patients with stigmata of recent haemorrhage (SRH) accessible to laser therapy were included in the trial (26 inaccessible, 96 no SRH). Patients were stratified into three groups--those with a visible vessel, those with other SRH, and those with clot that could not be washed off before therapy. Laser and control groups were well matched for other factors known to influence prognosis. Overall, 7/70 laser-treated and 27/68 control ulcers rebled (p less than 0.001). Rebleeding occurred from 6/39 treated and 23/43 control ulcers with a visible vessel (p less than 0.001); 0/17 treated and 1/13 ulcers with other SRH (NS); and 1/13 treated and 2/11 control ulcers with overlying clots (NS). 7/70 treated but 24/68 controls required emergency surgery (p less than 0.005). 1 treated patient but 8 control patients died after an episode of rebleeding (p less than 0.05).

Acute Disease↗
PubMed1986

Mortality from gastric cancer following gastric surgery for peptic ulcer.

When compared with a matched population group, 4466 ulcer patients who had had gastric surgery between 1940 and 1960 showed no difference in the risk of death from gastric cancer in the first 20 years of follow-up but a 4.5-fold increase thereafter. In duodenal ulcer patients there was an initial decrease in risk followed by a 3.7-fold increase after 20 or more years. Since the initial decrease was seen only in the gastrectomy patients and not in those who had truncal vagotomy and drainage, it may have been due to the reduction in mucosal surface. The increased risk 20 years after duodenal ulcer surgery was greater in vagotomy patients than in gastrectomy patients. In gastric ulcer patients a 3.0-fold increase in risk for the first 20 years rose to a 5.5-fold increase thereafter. After 20 years, patients treated with the Bilroth II operation were at higher risk than those treated with Bilroth I, consistent with a role for bile reflux in gastric carcinogenesis. The finding that the risk differs according to original pathology and type of operation may explain the discrepancies between previous studies.

Drainage↗
PubMed1986

Use of a gamma-labeled bile acid (75SeHCAT) as a test of ileal function. Methods of improving accuracy.

The object of the present study was to improve the accuracy of measurements of ileal function obtained by abdominal scanning and fecal counting after oral administration of the gamma-labeled bile acid 75seleno-homocholic acid-taurine (75SeHCAT), as current techniques do not distinguish between retention of the bile acid within the enterohepatic circulation from retention within the colon, and are also affected by incomplete stool collection when using the fecal method. We have therefore introduced the following modifications: (a) simultaneous ingestion of 51CrCl3 as a nonabsorbable correction marker for both the abdominal scanning and fecal counting methods; and (b) the use of 75SeHCAT counts over the gallbladder area on abdominal scanning, because these counts should be independent of colonic retention. We have studied 42 subjects, including 6 healthy controls, 6 ileal resection subjects, 15 ulcerative colitis patients, and 15 patients with unresected ileal Crohn's disease. Colonic retention (0%-68% per day) caused a variable overestimate of 75SeHCAT absorption. Corrected measurements of the fecal absorption index determined by a gamma-counter and of the abdominal absorption coefficient determined by a gamma-camera correlated well with each other (r = 0.92, p less than 0.0001), providing an internal validation of the 51CrCl3 modification. The fecal absorption index could also be determined from the carmine-rich stool collection of a single day, and this also correlated well with the abdominal absorption coefficient (r = 0.81, p less than 0.0001). Gallbladder scanning alone was simpler, involving only one isotope, but it correlated less well with the fecal absorption index than did the abdominal absorption coefficient (r = -0.64, p less than 0.001).

Adult↗
PubMed1986

Nature of the bleeding vessel in recurrently bleeding gastric ulcers.

An unselected consecutive series of 826 patients admitted for acute upper gastrointestinal bleeding underwent urgent endoscopy. Peptic ulcers were found in 402 (49%). Of the 329 ulcer craters that could be fully examined, visible vessels were identified in 156 (47%), other stigmata of recent hemorrhage in 66, and no stigmata of recent hemorrhage in 107. One hundred twenty-nine patients with stigmata of recent hemorrhage (93 of whom had visible vessels) randomly allocated to no endoscopic treatment were observed for evidence of further bleeding. Fifty-four of the 93 patients (58%) with visible vessels rebled, compared with 2 of 36 (6%) with other stigmata of recent hemorrhage. No patient without stigmata of recent hemorrhage rebled. Twenty-seven patients in whom a visible vessel in a gastric ulcer was identified at endoscopy underwent urgent partial gastrectomy because of recurrent bleeding. The vessel identified at endoscopy was found in 26 of 27 resection specimens (96%). The arterial vessel wall protruded above the surface of the ulcer crater in 10 specimens, and clot in continuity with a breach in the vessel wall protruded in a further 10 specimens. Postoperative angiography, when technically possible, showed that the breached artery ran across the base of the ulcer in all of these specimens. Pathological changes were common in the bleeding artery and included arteritis in 24 of 29 (83%) eroded arteries found in these specimens, with aneurysmal dilatation in 14 of 27 (52%) bleeding points that could be fully examined. The ulcer had penetrated to serosa in 13 specimens (45%). The bleeding artery had a mean external diameter of 0.7 mm with a range of 0.1-1.8 mm. This study provides new information about the nature of the bleeding vessel in gastric ulcers, and some of this information is relevant in planning studies of endoscopic therapy for bleeding peptic ulcers. It validates the endoscopic identification of a visible vessel, and confirms that such identification has a high predictive value for the development of recurrent hemorrhage.

Arteries↗
PubMed1986

Gallstone recurrence after medical dissolution. An overestimated threat?

We assessed gallstone recurrence rate in 42 patients diagnosed as having complete gallstone dissolution on bile acid therapy. By contrast with most previous studies, this diagnosis was based on ultrasound as well as on radiology, and only patients having their first gallstone recurrence were included in the study. Patients were followed for periods varying from 6 months to 7 years (median 30 months). Eleven patients had recurrences, giving an overall recurrence rate of 26%. A life analysis table was constructed by an actuarial method to compensate for the different lengths of follow-up in individual patients. Corrected recurrence rates by life table analysis were 15%, 21%, 25%, 36%, 45%, 45% and 45% at 1, 2, 3, 4, 5, 6 and 7 years respectively; for the same time intervals, cumulative recurrence rate overestimated the risk of gallstone recurrence (14%, 22%, 31%, 50%, 61%, 79% and 92%). We conclude that previous figures for recurrence rate have been an overestimate; but recurrence rate remains substantial over the first 5 years, and then levels off.

Actuarial Analysis↗