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Biomedical subjects

S G Thompson

Publications and source records attributed to S G Thompson.

At least 145 records · Page 8Linked to original sources

Simultaneous determination of phenytoin and phenobarbital in serum or plasma by substrate-labeled fluorescent immunoassay.

This assay system for simultaneously determining phenytoin and phenobarbital in serum and plasma is based on the substrate-labeled fluorescent immunoassay technique. A beta-galactosylcoumarin derivative of phenobarbital and a 4-methylcoumarin phosphodiester derivative of phenytoin are used as substrate labels for Escherichia coli beta-galactosidase and Crotalus atrox phosphodiesterase I, respectively. The smallest measurable concentrations are about 1.6 mg/L for phenytoin, 2.7 mg/L for phenobarbital. Within-run coefficients of variation are about 5% for phenytoin and 2% for phenobarbital, about 6% for both between-runs. Results for phenytoin and phenobarbital in serum and plasma correlate well with those determined by the Ames TDA (r = 0.944 and 0.986, respectively) and Syva's EMIT (r = 0.977 and 0.969, respectively) assays.

Humans↗

Seasonal variation in arterial blood pressure.

Blood pressure measurements recorded during the medical Research Council's treatment trial for mild hypertension have been analysed according to the calendar month in which the readings were made. For each age, sex, and treatment group systolic and diastolic pressures were higher in winter than in summer. The seasonal variation in blood pressure was greater in older than in younger subjects and was highly significantly related to maximum and minimum daily air temperature measurements but not to rainfall.

Adult↗

Haemostatic function and cardiovascular death: early results of a prospective study.

Components of the haemostatic system which may be involved in the pathogenesis of ischaemic heart disease (IHD) were measured in the Northwick Park Heart Study. Of 1510 white men aged 40-64 at recruitment, 49 have since died. 27 died from cardiovascular disease (IHD in all but 3), 18 from cancer, and 4 from other causes. The mean recruitment levels of factor VIIc, factor VIIIc, and fibrinogen were significantly higher in those who died of cardiovascular disease than in those who survived. The independent associations of factor VIIc and fibrinogen with cardiovascular death were at least as strong as the association of blood cholesterol with cardiovascular death. A clustering of two or three high clotting-factor values (factor VIIc, factor VIIIc, and fibrinogen) was present at recruitment in 63% of those who died of cardiovascular disease, compared with 23% of those who survived. The clotting-factor results appeared to be specific for cardiovascular disease: there was no evidence that high levels of factor VIIc, factor VIIIc, and fibrinogen were associated with death from cancer. The general epidemiology of factor VIIc, factor VIIIc, and fibrinogen is consistent with their having a role in the pathogenesis of IHD.

Adult↗

Progestogens and cardiovascular reactions associated with oral contraceptives and a comparison of the safety of 50- and 30-microgram oestrogen preparations.

Progestogens probably have metabolic effects that may contribute to the increased risk of cardiovascular reactions associated with combined oestrogen-progestogen oral contraceptives. This possibility was investigated by a study of nearly 2000 reports to the Committee on Safety of Medicines from 1964 to 1977. The reports concerned preparations in which norethisterone acetate in doses of 1.0, 2.5, 3.0, or 4.0 mg was combined with 50 microgram of ethinyloestradiol and those in which levonorgestrel in doses of 150 or 250 microgram was combined with 30 microgram of ethinyloestradiol. Observed and expected numbers of reports were compared, using retail pharmacy purchase figures as a measure of the use of different preparations. There was a significant positive association between the dose of norethisterone acetate and deaths from stroke and ischaemic heart disease (IHD); this association was also found for all cases of these two conditions, fatal plus non-fatal. There were no associations of dose of norethisterone acetate with hypertension or venous thrombosis. The higher dose of levonorgestrel was associated with a possible excess of deaths, non-venous plus venous, and an excess of strokes. There was no association between dose of levonorgestrel and hypertension or venous thrombosis. The reports were also used to assess the relative safety of 30-microgram and 50-microgram oestrogen preparations. Those with 30 microgram of oestrogen were associated with significantly fewer reports of death and IHD (both fatal, and fatal plus non-fatal) than those with 50 microgram of oestrogen. In view of the large-scale move towards preparations with progressively lower oestrogen doses, there are no grounds for major changes in oral contraceptive practice. Within the range of preparations currently in use, however, there is a case for minimising the dose of progestogen to reduce the chances of thromboembolism.

Cardiovascular Diseases↗

Substrate-labeled fluorescent immunoassay for amikacin in human serum.

A homogeneous substrate-labeled fluorescent immunoassay has been developed to measure amikacin levels in human serum. Amikacin is covalently labeled with the fluorogenic enzyme substrate beta-galactosyl-umbelliferone. This beta-galactosyl-umbelliferone-amikacin conjugate is nonfluorescent under assay conditions until it is hydrolyzed by beta-galactosidase to yield a fluorescent product. When antiserum to amikacin binds the substrate-labeled drug, the antibody complex formation inhibits hydrolysis of the fluorogenic substrate. Reaction mixtures containing a constant level of substrate-labeled amikacin and a limiting amount of antiserum enable labeled and unlabeled amikacin to compete for the antibody-binding sites. Unbound substrate-labeled drug is hydrolyzed by the enzyme to release a fluorescent product that is proportional to the unlabeled amikacin concentration. The amikacin levels found in clinical serum samples with this method were comparable (r = 0.987) to those obtained by radioimmunoassay. The fluorescent immunoassay is rapid and simple to perform and requires only 2 microliters of serum.

Amikacin↗

Reliable routine method for the determination of plasma amitriptyline and nortriptyline by gas chromatography.

A gas chromatographic method has been developed for the determination of amitriptyline and nortriptyline in plasma. OV-17 is used in a 1 m long packed column, with a flame ionization detector and an electronic integrator. Five internal standards are added. The base-specific extraction procedure and the method of calibrating the chromatograph are described in detail. The accuracy, precision and reliability of the method are demonstrated by the results of nearly 700 determinations of each drug, at concentrations ranging from 5 to 400 ng/ml in the plasma. An interlaboratory comparison with a double radioactive isotope derivative assay for nortriptyline has also shown satisfactory agreement.

Amitriptyline↗

Change in coronary risk and coronary risk factor levels in couples following lifestyle intervention. The British Family Heart Study.

OBJECTIVES: To measure the extent to which changes in cardiovascular risk factors were correlated among married couples following a 1-year primary care, family-centered, cardiovascular lifestyle intervention program and to identify couples who benefited most from this prevention program. DESIGN: Observational study. SETTING: Thirteen primary care centers in 13 towns in Britain. PARTICIPANTS: A total of 1477 men aged 40 to 59 years and their female partners who attended a family health checkup in 1991 to 1992 from randomly ordered invitations to registered families. After 1 year, 1204 (82%) partner pairs were rescreened. MAIN OUTCOME MEASURES: One-year changes in cigarette smoking, systolic blood pressure, serum cholesterol level, blood glucose level, and a total coronary risk score. RESULTS: Comparing men and women partners, baseline values and 1-year changes in overall coronary risk score (Pearson r = 0.27 and r = 0.20, respectively), cigarette smoking, body mass index, systolic blood pressure, cholesterol levels, and glucose levels were all positively correlated (all P < .001 except smoking cessation, P = .03). Changes in cholesterol levels and systolic blood pressure were also associated with partner's baseline measurement (P < or = .01 in both men and women). CONCLUSIONS: Men and women who benefit most from risk factor reductions have partners who also tend to benefit most. Conversely, men and women who enjoy little or no benefit have partners who tend to have similarly small benefits. It is likely that lifestyle intervention targeted at men and women as couples rather than as individuals may result in a greater reduction in cardiovascular risk factors, possibly through mutual reinforcement of lifestyle changes.

Adult↗