Search PubMed⌕ Search

Biomedical subjects

G D Bell

Publications and source records attributed to G D Bell.

At least 109 records · Page 6Linked to original sources
PubMed1987

Intravenous midazolam: a study of the degree of oxygen desaturation occurring during upper gastrointestinal endoscopy.

Intravenous midazolam (mean dose of 6.3 mg) was given to 100 consecutive patients coming to endoscopy. All patients had an ear oximeter attached throughout the procedure to record continuously their levels of oxygen saturation. Eighty-five of the 100 patients had pre-endoscopy respiratory function tests measured, and 82 wore an induction plethysmograph vest to get a continuous qualitative estimate of respiratory rate and excursion throughout the procedure. Following intravenous midazolam a reduction in respiratory excursion was observed in 80% of patients. The initial baseline oxygen saturation of 95.4% fell 3.3% (P less than 0.0005) following intravenous midazolam to 92.1%. During the endoscopic procedure there was a further 3.1% decrease in oxygen saturation to 89.0% (P less than 0.0005) and in 7% the level fell to below 80%. Age, sex, dose of midazolam given and pre-endoscopy respiratory function tests failed to identify those patients at risk of hypoxia during the endoscopy.

Adult↗
PubMed1987

Salivary secretion of paracetamol in man.

Plasma and saliva paracetamol levels were measured by HPLC in ten healthy volunteers who took a therapeutic dose after an overnight fast. Salivary levels of the drug were consistently and significantly higher than those in plasma for the first 50 min after oral ingestion, but saliva and plasma levels correlated closely during the elimination phase. There was a highly significant correlation between the AUC 0-alpha calculated from saliva and plasma paracetamol concentration-time curves. The elevated saliva/plasma ratio for the first 50 min was not due to loss of paracetamol from plasma during sample preparation, binding to plasma protein or adsorption to the buccal mucosa. Administration of probenecid in an attempt to block possible active secretion of paracetamol into saliva did not significantly alter the saliva/plasma concentration ratio for the first 50 min, but did significantly reduce this ratio in the time period 125-360 min. The experimental data conformed to a recently proposed model in which elevated saliva/plasma ratios during the early stages following oral ingestion were related to ongoing absorption into the arterial system.

Acetaminophen↗
PubMed1987

Temporal variations in paracetamol absorption and metabolism in man.

When paracetamol (1.5 g) was administered orally to non-fasted healthy subjects, statistically significantly more paracetamol glucuronide was detected in 0-4 h urine when the drug was given at 8.00 a.m. as compared to other times of the day. Compared to administration at 8.00 pm, the urine contained almost twice as much glucuronide. However, there was apparently no temporal variation in the excretion of intact drug and its other metabolites. Marked differences were observed in salivary concentrations of paracetamol during the first 90 min following oral administration at 8.00 a.m. and 8.00 p.m. These data were consistent with a decreased rate of absorption of paracetamol at 8.00 p.m. Paracetamol clearance, elimination half-life and volume of distribution did not differ when the drug was administered by intravenous infusion at 8.00 a.m. and 8.00 p.m. There was also no change in the amounts of paracetamol and metabolites excreted in the urine. There appears to be a temporal variation in the elimination of paracetamol glucuronide following oral administration of paracetamol, which is probably related to a variation in absorption.

Acetaminophen↗
PubMed1985

In-vitro enhancement of cholesterol dissolution by commonly used drugs.

A rotating disc apparatus was used to study the dissolution of cholesterol in sodium cholate solutions and ox bile. Drugs with structures that render them capable of lowering interfacial resistance were tested and shown to increase cholesterol dissolution rates in both systems. In sodium cholate solutions, loperamide (3 X 10(-4)M) increased the rate of dissolution by over six times, and a similar effect was observed with amitriptyline (3 X 10(-3)M), diphenhydramine (3 X 10(-3)M), dicyclomine (3 X 10(-3)M) and propantheline (3 X 10(-3)M). These drugs are as effective as benzalkonium chloride at these concentrations. Amitriptyline, propantheline, dicyclomine and diphenhydramine also increased cholesterol dissolution rates into ox bile. If these drugs are excreted into human bile in sufficient quantities and in an active form they may be able to enhance the speed of cholesterol gallstone dissolution therapy.

Animals↗
PubMed1985

Stones in the common bile duct: experience with medical dissolution therapy.

Thirty-one patients with radiolucent common bile duct stones received medical treatment. Nineteen had Rowachol, a terpene preparation, eight (42%) achieving complete stone disappearance within 3 to 48 months. Fifteen (including 3 of the above) took Rowachol with bile acid (chenodeoxycholic in 11, ursodeoxycholic in 4) for 3 to 60 months: 11 (73%) achieved complete dissolution within 18 months. Persistent symptoms and complications settled on conservative management: 8 (25%) patients required admission (2 biliary colic, 1 obstructive jaundice, 4 cholangitis, 1 pancreatitis). One patient died of a myocardial infarction during recovery from pancreatitis; the other continued treatment, 2 achieving complete dissolution/disappearance. Oral dissolution therapy with Rowachol and bile acids should be considered when endoscopic sphincterotomy or surgery is not feasible, but careful attention to potential complications is required while stones persist.

Adult↗
PubMed1984

Pilot study of combination treatment for gall stones with medium dose chenodeoxycholic acid and a terpene preparation.

Thirty patients with radiolucent stones in a radiologically functioning gall bladder were treated for up to two years with a combination of Rowachol (one capsule twice daily), a mixture of cyclic monoterpenes, and chenodeoxycholic acid (7.0-10.5 mg/kg/day). The patients were not selected for body weight or size of stones. All complete dissolutions diagnosed by oral cholecystography were confirmed or refuted by ultrasound examination. Control of symptoms was excellent, only one patient withdrawing from the study because of persistent biliary pain. No evidence of hepatotoxicity was detected biochemically, and diarrhoea due to chenodeoxycholic acid was minimal at this dose. Stones disappeared completely in 11 patients (37%) within one year and in 15 (50%) within two years. These results compared favourably with those obtained with similar doses of chenodeoxycholic acid alone, in particular those of the National Co-operative Gallstone Study (complete dissolution in 13.5% of patients at two years). Treatment with a combination of medium dose chenodeoxycholic acid with Rowachol for radiolucent gall stones is economical, effective, and likely to minimise persistent symptoms and adverse effects of treatment.

Adult↗
PubMed1984

Delayed release peppermint oil capsules (Colpermin) for the spastic colon syndrome: a pharmacokinetic study.

Excretion of menthol (as glucuronide) from orally ingested peppermint oil contained in Colpermin was compared with oil contained in two soft gelatine capsules. Total 24 h urinary excretion of menthol was similar in the two formulations in healthy volunteers, but peak menthol excretion levels were lower and excretion delayed with Colpermin. Menthol excretion was reduced in ileostomy patients who took Colpermin and moderate amounts of unmetabolised menthol were recovered from the ileostomy effluent. This is consistent with Colpermin being a delayed-release form of peppermint oil.

Adolescent↗
PubMed1984

The effects of 3,5,5-trimethylcyclohexanol on hepatic cholesterol synthesis, bile flow and biliary lipid secretion in the rat.

The chemical trimethylcyclohexanol (TMC) is closely related to menthol, the major component of a terpene preparation with known choleretic and cholelitholytic activity. Its effects on hepatic cholesterol synthesis and bile secretion were examined in the rat. In both acute and long-term dosing experiments TMC significantly inhibited hepatic S-3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase. TMC was a potent choleretic, with detectable effects on bile flow at low doses, which also reduced coupling of cholesterol secretion to bile salt secretion. Single large doses tended to lower biliary cholesterol output and caused significant reduction in cholesterol saturation index after biliary diversion for 1 h. TMC and its widely prescribed ester cyclandelate, which is rapidly degraded to TMC after ingestion, should be investigated further as potential cholelitholytic treatments in man.

Animals↗
PubMed1984

An unusual cause of variceal haemorrhage in an elderly patient.

An elderly patient with nodular regenerative hyperplasia of the liver and hypothyroidism who presented with life-threatening bleeding from oesophageal varices is discussed. Progress has been uneventful following a semi-emergency portocaval shunt 5 years ago with no evidence of hepatic encephalopathy. This is presumably a tribute to the relatively well-preserved hepatic function in this condition.

Aged↗
PubMed1983

In vivo inhibition of hepatic lipogenesis in the rat by cyclandelate (3,3',5-trimethylcyclohexanylmandelate).

Rates of hepatic lipogenesis were measured in vivo in rats by incorporation into lipids of [3H] from injected [3H]H2O 17 hr after a single oral dose of cyclandelate (3,3',5-trimethylcyclohexanylmandelate, a vasoactive substance). Cyclandelate administration resulted in a significant inhibition (40-60%) of both sterol and fatty acid synthesis in the livers which was independent of the 3.2-fold diurnal variation in the rates of hepatic sterol and fatty acid synthesis. The inhibition of accumulation of newly synthesized fatty acid in intestine also reached statistical significance. The accumulation of newly synthesized sterol was significantly depressed in serum but did not result in any change in the concentration of serum total cholesterol. These results are interpreted in terms of the inhibitory effect of cyclandelate on hepatic 3-hydroxy-3-methylglutaryl-CoA reductase previously reported by us (Biochem. Pharmac. 32, 649, 1983).

Animals↗
PubMed1983

The inhibition of hepatic S-3-hydroxy-3-methylglutaryl-CoA reductase by 3,3,5-trimethylcyclohexanol and its mandelic acid ester, cyclandelate.

Rat hepatic HMGCoA reductase was found to be at least 50% inhibited 17 hr after administration of a single oral dose of 3,3,5-trimethylcyclohexanyl mandelate (cyclandelate), a vasoactive substance. This inhibition was also found in rats given the 3,3,5-trimethylcyclohexanol component but only slight inhibition was seen after an equimolar dose of mandelate. The inhibition of HMGCoA was observed both around the high point and near the low point of the diurnal activity cycle. The effect did not persist to 41 hr after treatment. There was no direct inhibition of HMGCoA reductase by trimethylcyclohexanol when added to the assay system in vitro. The in vivo effect of these inhibitors was specific for HMGCoA reductase. There was no change, neither elevation nor depression, of the amount of microsomal membrane components cytochromes b5 and P-450, not was the activity of another microsomal enzyme, arylesterase, affected by dosing with cyclandelate or trimethylcyclohexanol.

Administration, Oral↗
PubMed1982

Gall-stone dissolution and recurrence: are we being misled?

Oral cholecystography repeated at six-months intervals is the standard method for determining reduction in size of gall stones (partial success) and complete dissolution of stones (complete success). In a comparative study of oral cholecystography and cholecystosonography six out of 14 patients with gall stones achieving complete success by oral cholecystographic criteria had stones still detectable by ultrasonography. Repeat oral cholecystography in a further 11 patients receiving post-dissolution maintenance treatment detected stones in two, whereas ultrasonography detected stones in seven. In future complete dissolution of gall stones should be reported only if both oral cholecystography and ultrasonographic studies give negative results and the progress of patients receiving post-dissolution maintenance treatment is monitored by ultrasonography rather than serial oral cholecystography.

Chenodeoxycholic Acid↗
PubMed1982

The mechanism of cyclic monoterpene inhibition of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase in vivo in the rat.

Seventeen hours after a single oral dose of the cyclic monoterpenes cineole or menthol, rat liver 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity was inhibited by up to 70%. The transient nature of this effect (no inhibition 41 h after dosing) was compatible with the rapid metabolism and excretion of these terpenes. Neither menthol, and its major metabolite, menthylglucuronide, nor cineole acted as direct inhibitors of HMG-CoA reductase activity in vitro, although menthol was found to bind to liver microsomes Ks approximately 0.1 mM). Unlike the short term effects of dietary cholesterol, terpene administration did not affect HMG-CoA reductase activity by modulation of the lipid microenvironment of the enzyme. Thus, following menthol or cineole treatment, we found no deviations from the normal kinetic responses to changes in temperature or in concentration of HMG-CoA. Furthermore, the inhibitory effect was still seen after solubilization of the enzyme from microsomes. The loss of HMG-CoA reductase activity was not associated with increased phosphorylation of the enzyme. Immunotitration of HMG-CoA reductase from terpene-treated rats showed that activity loss was due to less enzyme molecules (together with some possibly "cripple" enzyme), indicating that rates of enzyme synthesis or degradation had been altered. Since menthol inhibition of reductase was still observed in rats deprived of foods, we conclude that the effect is not mediated by those hormones whose concentration is changed during fasting (insulin, glucagon, and adrenaline).

Animals↗
PubMed1982

Outcome of endoscopy and barium radiography for acute upper gastrointestinal bleeding: controlled trial in 1037 patients.

A study was conducted to find whether the higher diagnostic yield of endoscopy compared with barium radiography improves management or survival in patients with acute upper gastrointestinal bleeding. A total of 1037 patients were entered into a randomised study comparing the outcomes after each investigation. The diagnostic yield in patients who underwent endoscopy was 73% (382 of 526 cases) and in those examined by radiography 55% (280 of 511 cases). A fifth of the patients in the radiology group and a tenth of those in the endoscopy group subsequently underwent the alternative investigation; in most cases, however, no additional diagnostic information was obtained. Operation rates were similar in two groups, though patients in the endoscopy group were generally operated on sooner. Mortality rates were also similar in the two groups, though postoperative mortality was higher in the endoscopy group. Endoscopy may be a more accurate means of diagnosis than radiography, but it offers no short-term benefits in management.

Clinical Trials as Topic↗