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Biomedical subjects

G D Bell

Publications and source records attributed to G D Bell.

At least 127 records · Page 7Linked to original sources

Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme a reductase, in healthy volunteers.

Mevinolin reduces cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The safety and effectiveness of this agent was evaluated in a double-blind, placebo-controlled study in 59 healthy men (serum cholesterol 3.88--7.76 mmol/liter) in five centers. Subjects maintained their usual diet and activities. Doses of 6.25, 12.5, 25, or 50 mg twice daily for 4 wk produced mean reductions of total serum cholesterol fo 23--27% [vs. placebo (4%), P less than 0.01]. Mean low density lipoprotein cholesterol fell 35--45%, while high density lipoprotein and very low density lipoprotein cholesterol, and triglycerides were not significantly affected. Mean apolipoprotein B fell 27--34%. 50 mg was not significantly more effective than 6.25 mg. Mevinolin was generally well tolerated, and no serious clinical or laboratory abnormalities occurred. One subject (12.5 mg) was withdrawn because of abdominal pain and diarrhea. These results suggest that if long-term safety can be demonstrated, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase are likely to prove useful in the treatment of hypercholesterolemia.

Adolescent↗

Glucagon and infusion cholangiography.

It has been previously suggested that glucagon improves the bile duct and gall-bladder opacification obtained by infusion cholangiography. One hundred and ninety consecutive patients referred for intravenous cholangiography were entered into a double-blind study designed to see if glucagon would in fact significantly improve bile duct opacification. All patients received a one hour intravenous infusion of iotroxamide at a rate of 3.15 mg/kg body weight/min. Glucagon did not enhance bile duct opacification, the mean post-injection scores for the two groups being 2.47 +/- 1.11 and 2.29 +/- 1.15 respectively. On the basis of the present study we cannot recommend the routine use of glucagon following infusion cholangiography.

Bile Ducts↗

The effect of cholesterol feeding on gallbladder bile acids of the rabbit. Evidence that lithocholic acid is a primary bile acid in the rabbit.

The bile acid in gallbladder bile of rabbits fed a normal diet or one containing 2% (w/w) cholesterol have been determined by gas chromatography-mass spectrometry. The predominant bile acids in normally fed rabbits were 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholan-24-oic acid (cholic acid), 3 alpha, 12 alpha-dihydroxy-5 alpha-cholan-24-oic acid (allodeoxycholic acid) and 3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acid (deoxycholic acid) with very much smaller amounts of 3 alpha-hydroxy-5 beta-cholan-24-oic acid (lithocholic acid) and 3 alpha, 12 beta-dihydroxy-5 beta-cholan-24-oic acid. In the cholesterol-fed animals the lithocholate became a predominant bile acid. Sulphated bile acids accounted for less than 1% of the total bile acids. It is proposed that lithocholic acid may be a primary bile acid in the cholesterol-fed rabbit, formed by an alternative pathway of biosynthesis involving hepatic mitochondria.

Animals↗

Intraductal infusion of mono-octanoin: experience in 24 patients with retained common-duct stones.

Mono-octanoin (glyceryl-l-mono-octanoate), 2-4 ml/h, was instilled into the bile or hepatic ducts of twenty-four patients with retained gallstones after cholecystectomy and choledochotomy. After treatment, fifteen patients no longer had stones. In five the stones were smaller or reduced in number; and in four of these the stones were extracted mechanically via the T-tube tract. Mechanical extraction was also possible in one of the four patients with unaltered stones. With a battery-operated pump or hand injection, mono-octanoin can be safely infused as early as the 8th postoperative day and some patients can continue the treatment outside hospital.

Adolescent↗

Cimetidine and ranitidine: comparison of effects on hepatic drug metabolism.

Paired studies of hepatic microsomal function were conducted in eight subjects during treatment with two histamine H2 antagonists, cimetidine and ranitidine. Cimetidine but not ranitidine inhibited the metabolism of antipyrine (phenazone) and demethylation of aminopyrine (aminophenazone) as measured by breath 14CO2 production after intravenous injection of 14C-aminopyrine. These results suggest that the metabolic inhibitory actions on the liver may be separated from H2 antagonist effects, and that ranitidine has an advantage over cimetidine by not inhibiting microsomal drug oxidative function.

Aminopyrine↗

Elevation of serum high density lipoprotein cholesterol by rowachol, a proprietary mixture of six pure monoterpenes.

Rowachol, a proprietary choleretic containing 6 pure monoterpenes markedly elevates serum HDL cholesterol (SHDL-C) concentrations in man. The concentration of SHDL-C showed a progressive increase in 16 patients treated with 6-9 capsules of Rowachol daily for periods of 2-28 weeks. There was no accompanying significant change in the concentrations of serum total cholesterol or triglyceride. In view of the significant inverse relationship between SHDL-C concentration and the risk of developing ischaemic heart disease, it is suggested that Rowachol and possibly other terpenes merit further investigation as possible therapeutic agents in the prevention and treatment of atheroma.

Adolescent↗

Iotroxamide studies in man--biliary iodine levels following bolus injection and slow infusion. Comparison with ioglycamide.

The concentration of iodine in the bile of patients with indwelling T-tubes has been measured following administration of the new cholangiographic agent Iotroxamide. Studies have been performed after administration of the contrast agent by both 10 min bolus injection and 1 h drip infusion techniques. Comparison has been made with the iodine concentrations obtained after administration of equimolar amounts of Ioglycamide. There was no significant difference in the biliary iodine levels obtained with the two methods of administration when Iotroxamide was the contrast agent employed. However, with Ioglycamide the slow infusion technique produced higher iodine levels than the bolus injection method (P less than 0.05). Comparison between the two agents reveals that, whichever administration technique is used, Iotroxamide provides higher iodine levels than Ioglycamide. After bolus injection the superiority for Iotroxamide is in the region of 20% and after slow infusion is of the order of 10--15%. It is concluded that Iotroxamide is likely to prove superior to Ioglycamide as a cholangiographic agent. In terms of opacification of the biliary tree there is little to choose between bolus injection and slow infusion techniques when using Iotroxamide and the relative toxicity of the two techniques should be the major factor in determining which method is employed in clinical practice.

Bile↗

Effect of intravenous glucagon on the biliary secretion of a cholangiographic agent in man.

This study was undertaken in an attempt to define the mechanism whereby intravenous glucagon enhanced bile duct and gallbladder opacification at the time of infusion cholangiography. Seven post-operative gallstone patients with indwelling t-tubes were given a 1 h infusion of intravenous iotroxamide at a rate of 4.1 mg/kg body weight/min. Bile samples were collected by gravity drainage and assayed for iotroxamide and hence biliary iodine concentration. At the end of the 1 h infusion the mean biliary excretion rate (+/- s.e.m.) of iotroxamide was 26.1 +/- 3.4 mg/min and the iodine concentration in bile 9.7 +/- 1.2 mg/ml. 1 mg of intravenous glucagon given over 30 s at the end of the iotroxamide infusion produced a significant increase in bile flow (P less than 0.01). The excretion rate of iotroxamide rose rapidly following glucagon to reach a peak value of 43.8 +/- 8.1 mg/min 5 min after the glucagon (P less than 0.05). The enhanced biliary excretion of iotroxamide resulting from the glucagon injection was significant (P less than 0.05) 1, 3 and 5 but not 10 min after the hormone. The intravenous glucagon also caused a small but significant (P less than 0.05) elevation of the biliary iodine concentration to 10.9 +/- 1.2 mg/ml, 3 min after its injection, but by 5 min post-glucagon the iodine concentration in bile had reversed to pre-injection levels. The possible clinical implications of these results are discussed.

Adult↗

Iotroxamide--a new cholangiographic agent. Relation between plasma concentration and biliary excretion in man.

The relationship between infusion rates, plasma concentration and biliary excretion of iotroxamide were studied in 24 patients with a T-tube in situ. Plasma iotroxamide concentration was linearly related to the rate of infusion over a dose range of 0.525 to 6.3 mg/kg/min. Peak biliary concentrations and excretory rates of iotroxamide were seen when the plasma concentration was of the order of 1500 microgram/ml. The results suggest that when using a one hour infusion of iotroxamide near optimal concentrations of iodine in the bile duct can be achieved with an infusion rate of around 4 mg/kg/minute. No toxic effects were noticed from the use of this new cholangiographic agent.

Bile↗

Drip infusion cholangiography using iotroxamide. Double blind comparison with ioglycamide.

A double blind clinical trial was carried out in 200 unselected patients to compare the efficacy and tolerance of ioglycamide and iotroxamide as contrast media for intravenous cholangiography. The two agents were administered by slow infusion at a rate of 2.6 mumoles/kg bodyweight/minute for one hour. Radiological opacification of the bile duct was assessed independently by two radiologists. In patients with serum bilirubin levels of less than 34 mumoles/litre visualization of the bile duct was significantly better with iotroxamide than with ioglycamide (P < 0.001). Toxic side effects were observed in 8% of patients receiving ioglycamide and in only 3% of the patients given iotroxamide.

Adult↗