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Biomedical subjects

S M Gibson

Publications and source records attributed to S M Gibson.

7 recordsLinked to original sources
PubMed2001

MHC class II region, CTLA4 gene, and ophthalmopathy in patients with Graves' disease.

Up to half of patients with Graves' hyperthyroidism have signs of thyroid associated ophthalmopathy, but the factors that cause this disorder are unknown. We investigated two major genetic susceptibility loci for Graves' disease in ophthalmopathy; the MHC class II region and the cytotoxic T lymphocyte antigen-4 (CTLA4) gene. Allelic frequencies of these genes in patients with Graves' disease who did and did not have concurrent thyroid-associated ophthalmopathy did not differ, and are, therefore, unlikely to contribute to its development.

Abatacept↗
PubMed1999

Double-blind placebo-controlled trial of digoxin in symptomatic paroxysmal atrial fibrillation.

BACKGROUND: Digoxin is commonly prescribed in symptomatic paroxysmal atrial fibrillation (AF) but has never been evaluated in this condition. METHODS AND RESULTS: From a multicenter registry, 43 representative patients with frequent symptomatic AF episodes were recruited into a randomized, double-blind crossover comparison of digoxin (serum concentration, 1.29+/-0.35 nmol/L) and placebo. The study end point was the occurrence of 2 AF episodes (documented by patient-activated monitors), censored at 61 days. The median time to 2 episodes was 13.5 days on placebo and 18.7 days on digoxin (P<0. 05). The relative risk (95% CI) of 2 episodes (placebo:digoxin) was 2.19 (1.07 to 4.50). A similar effect was seen on the median time to 1 episode: increased from 3.5 to 5.4 days (P<0.05), relative risk 1. 69 (0.88 to 3.24). The mean+/-SD ventricular rates during AF recordings during placebo and digoxin treatment were 138+/-32 and 125+/-35 bpm, respectively (P<0.01). Twenty-four-hour ambulatory ECG recordings did not show significant differences in the frequency or duration of AF or in ventricular rate. CONCLUSIONS: Digoxin reduces the frequency of symptomatic AF episodes. However, the estimated effect is small and may be due to a reduction in the ventricular rate or irregularity rather than an antiarrhythmic action.

Ambulatory Care↗
PubMed1993

Weekly treatment of diet/drug-resistant hypercholesterolemia with the heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) system by selective plasma low-density lipoprotein removal.

Heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) weekly therapy was evaluated for safety and efficacy in selectively reducing LDL cholesterol levels. Weekly treatments (25) were given to high-risk hypercholesterolemic patients (n = 33) with screening LDL cholesterol levels > 160 mg/dl despite prior diet and drug therapy. Lipids, lipoprotein cholesterol, apolipoproteins A-l and B, and fibrinogen were measured on plasma samples before and after treatment. Mean plasma volume treated was 2.66 liters and mean treatment duration 1.7 hours. Therapy complications were infrequent and were primarily vascular access problems or hypotension. Treatment goals were > 30% LDL cholesterol reduction with each treatment. In 98% of 686 HELP treatments, LDL cholesterol levels were reduced > or = 30%. Mean LDL cholesterol levels were reduced 111.0 mg/dl (54%) with a time-averaged decrease of 39% over a 25-week course. Mean HDL cholesterol was reduced only 6.2 mg/dl (15%). Total cholesterol (134.4 mg/dl; 47% decrease) and apolipoprotein B (88.7 mg/dl; 53% decrease) levels were also reduced. Fibrinogen decreased 158.2 mg/dl (58%) without bleeding complications. HELP therapy can safely and selectively remove plasma LDL cholesterol, producing consistent reductions in LDL cholesterol, total cholesterol and apolipoprotein B levels.

Apolipoproteins B↗
PubMed1977

Carbon-13 nuclear magnetic resonance probe of active-site ionizations in human carbonic anhydrase B.

Human carbonic anhydrase B (HCAB), prepared by a new affinity chromatography procedure, was carboxymethylated exclusively at NT of its active-site histidine-200 using 90% [1-13C]bromoacetate. The 13C nuclear magnetic resonance signal of the covalently attached carboxylate was easily detected over the natural abundance background due to the other carbonyl and carboxyl carbons of this 29 000 molecular weight zinc metalloenzyme. Its chemical shift proved very sensitive to the presence of inhibitors in the active site and to variations in pH. Two perturbing groups with pKa values of 6.0 and 9.2 were assigned to the modified histidine-200 itself and the zinc-bound water ligand, respectively, making use of 13C NMR titration data on Nr- and Nr-carboxymethyl-L-histidine model compounds. The results rule out histidine-200 as the critical group whose ionization controls the catalytic activity. They also strongly suggest an interaction of the carboxylate of the carboxymethyl group with either the zinc or its water ligand around pH 8, possibly explaining the basis for the major differences between HCAB and CmHCAB.

Acetates↗