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Biomedical subjects

B J Burton

Publications and source records attributed to B J Burton.

11 recordsLinked to original sources
PubMed1998

Steroid-responsive HIV optic neuropathy.

A 37-year-old man with bilateral optic neuropathy who recovered on steroid treatment is described. He was subsequently found to be human immunodeficiency virus 1 (HIV-1) positive prior to the onset of his visual symptoms, and no other cause of his optic neuropathy could be found. There is some evidence that HIV itself may be a cause of symptomatic optic neuropathy. A spontaneously relapsing and remitting multiple sclerosis-like syndrome has previously been described in HIV-positive patients, and this may present with optic neuritis. A chronic optic neuritis in HIV-positive patients that is not usually symptomatically important has also been described. We review the literature related to these topics and our patient.

Adult↗
PubMed1997

Granular cell tumour of the spinal cord in a patient with Rubenstein-Taybi syndrome.

A case of cervical spinal cord granular cell tumour in a patient with Rubenstein-Taybi syndrome is described. A granular cell tumour arising from the spinal cord itself has never been previously described. Complete excision of the tumour could not be achieved owing to its location. It subsequently recurred and was treated with radiotherapy. The patient made a complete recovery with no further recurrence after 2 years of follow-up.

Adult↗
PubMed1996

Hypolipidaemic properties of a potent and bioavailable alkylsulphinyl-diphenylimidazole ACAT inhibitor (RP 73163) in animals fed diets low in cholesterol.

RP 73163 ((S)-2-[5-(3,5-dimethyl-l-pyrazolyl)pent-l-yl)-sulphinyl]-5, 6-diphenylimidazole) has been shown to be a potent and specific inhibitor of acyl-CoA:cholesterol acyltransferase (EC 2.3.1.26; ACAT) in vitro using the tissues of experimental animals as sources of the enzyme. The concentrations of RP 73163 required to produce 50% inhibition of ACAT activity (IC50 values) in microsomal preparations ranged from 86 nM for rat liver to 370 nM for rabbit intestine. In whole cell assays using human hepatic (HepG2), intestinal (Caco2), and monocytic (THP-1) cell lines, RP 73163 inhibited ACAT activity with IC50 values of 266, 158, and 314 nM, respectively. The addition of RP 73163 (0.03-1.0 microM) to the medium of cultured HepG2 cells produced a concentration-dependent decrease in apolipoprotein B (apoB) secretion. The compound has high systemic bioavailability. Using a bioassay, a concentration of active inhibitor equivalent to 29 microM of parent compound was present in plasma 1 hr after oral administration of RP 73163 (50 mg.kg-1). In rats that had been fed a basal diet ad libitum or starved for 18 hr prior to blood sampling, the administration of RP 73163 (50 mg.kg-1 b.i.d. for 7 days) reduced plasma triglyceride levels by 50% without affecting the concentration of cholesterol. This hypotriglyceridaemic effect was associated with reductions in plasma very-low-density-lipoprotein (VLDL) and low-density-lipoprotein (LDL) levels. RP 73163 decreased the rate of VLDL secretion by 24% in Triton WR-1339-treated rats that had been fasted overnight but did not affect the secretion rate in animals fed ad libitum, indicating that ACAT was only important in regulating VLDL secretion under certain nutritional conditions. RP 73163 reduced the accumulation of intraperitoneally administered [3H]leucine into the plasma VLDL-apoB pool in both fed and fasted states. The results suggest that, in fed animals at least, an increase in the clearance of VLDL from the bloodstream may contribute to the hypolipidaemic activity of the compound. In rabbits with casein-induced endogenous hypercholesterolaemia, RP 73163 specifically reduced the levels of cholesterol carried by LDL. In conclusion, the hypolipidaemic actions of RP 73163, a potent and systemically bioavailable ACAT inhibitor, are consistent with a reduction in the secretion of apoB containing lipoproteins by hepatic tissue and possibly with an increase in the clearance of these particles.

Animals↗
PubMed1996

RP 64477: a potent inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase with low systemic bioavailability.

RP 64477 (N-butyl-3-(p-decyloxybenzamido)-4-(methylthio)benzamide) has been shown to be a potent inhibitor of the cholesterol esterifying enzyme Acyl-coenzyme A:cholesterol O-acyltransferase (EC 2.3.1.26; ACAT) in intestinal, hepatic, adrenal, and arterial tissue preparations obtained from a range of animal species. Drug concentrations producing 50% inhibition of enzyme activity (IC50 values) ranged from 14-283 nM. Inhibition by RP 64477 in a rabbit intestinal enzyme preparation was shown to be non-competitive with respect to the substrate oleoyl-CoA. In whole cell assays using human intestinal (CaCo-2), hepatic HepG2) and monocytic (THP-1) cell lines, RP 64477 inhibited ACAT activity with IC50s of 113, 503, and 180 nM, respectively. RP 64477 (0.03% w/w by diet) reduced significantly cholesterol absorption in cholesterol/cholic acid-fed rats from 94+/- 8% to 65 +/- 4%. In cholesterol-fed rabbits, cholesterol absorption was reduced from 72 +/- 5% to 50 +/-5% and 44 +/- 5% at dose levels of 10 and 30 mg kg-1 b.i.d., respectively. Plasma cholesterol levels were reduced dose-dependently in both cholesterol/cholic-acid-fed rats and cholesterol-fed rabbits. Neither cholesterol absorption nor plasma cholesterol levels were reduced significantly in animals maintained on standard laboratory diets. Pharmacokinetic studies indicated that RP 64477 were very poorly absorbed following oral administration to rats. Plasma levels of drug were < 2 ng mL-1 following a dose of 2000 mg kg-1 p.o.. When radiolabelled RP 64477 was administered orally, limited absorption was indicated by the overwhelming elimination of radioactivity in the faces (96.4% of administered material) coupled with low renal clearance (0.6% of dose) and biliary excretion (0.05% of dose). In conclusion, this work shows that RP 64477 is a potent inhibitor of ACAT obtained from a range of animal species and man. Inhibition of cholesterol absorption and hypocholesterolaemic activity has been demonstrated in rats and rabbits maintained on diets supplemented with cholesterol. Pharmacokinetic studies indicate low systemic exposure to RP 64477 as a result of limited absorption of this drug.

Acyl Coenzyme A↗
PubMed1995

Aortic root replacement and extraanatomic bypass for interrupted aortic arch in an adult.

We describe an unusual case of interrupted aortic arch, aneurysmal ascending aorta, and aortic regurgitation in a 24-year-old man. He presented with general malaise, weakness of his legs, and hypertension. A single-stage operation was performed in which the aortic root was replaced with concomitant extraanatomic bypass of the interrupted segment of the aortic arch. He made a full recovery and has returned to work.

Adult↗
PubMedDate not supplied

Phaeochromocytoma.

Phaeochromocytomas are rare catecholamine-secreting tumours which can mimic a variety of common clinical conditions, such as hypertension and angina. It is a potentially curable condition if discovered early, and clinicians should be alerted as to its presence in a young individual with hypertension or atypical angina-associated hypertension. Pharmacological mismanagement can cause fatal hypertensive crisis.

Adolescent↗