A stereoselective synthesis of two stereoisomers of demethylgorgosterol.
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Methods↗
Biomedical subjects
G D Anderson
Publications and source records attributed to G D Anderson.
Listeria monocytogenes septicemia in pregnancy.
A case of Listeria monocyto-enes septicemia in a patient with a poor reproductive history is presented. The clinical aspects and implications of this infectious disease during pregnancy are discussed, and the role of Listeria as a cause of recurrent pregnancy wastage is summarized.
Adult↗
Concordance for coronary risk factors among spouses.
Values for several coronary risk factors, including systolic and diastolic blood pressure, serum cholesterol, triglycerides, blood glucose, uric acid, hemoglobin, weight, vitral capacity and cigarette smoking have been found to be similar among spouses in the Framingham Study. However, longitudinal analyses show that this spouse concordance does not increase over a twelve-year observation period, suggesting that it has arisen through the marriage of similar people rather than through the sharing of a common marital environment. Apparent conflicts between cross-sectional and longitudinal findings have been resolved by showing that spouses who were concordant at the begining of the study are more likely to survive to later exams, while discordant spouse pairs tend to be dissolved through the death of one of their members.
Adult↗
Comparison of provincial surgical rates in 1968.
Studies have been made of age- and sex-adjusted 1968 provincial rates for individual surgical procedures. For elective and discretionary operations, such as tonsillectomy and adenoidectomy, hysterectomy, vein stripping and lens extraction, provincial rates varied by approximately 100 percent. Newfoundland, with few surgeons and hospital beds, had the lowest discretionary rates, and Alberta, which ranked hgih both for surgeons and hospital beds, the highest. Interprovincial differences were of smaller magnitude for non-discretionary surgery (radical mastectomy, cesarean section, colectomy., lobectomy, etc.). Ther were statistically significant correlations between numbers of surgeons and elective and discretionary surgical rates and between numbers of hospital beds and bed use in the provinces. The effect of disease prevalence on discretionary surgical rates was minimized because the rates were age- and sex-adjusted. Provincial organization of, and payment for, medical services has been similar. Hence, the ratio of surgical personnel to population in each province is postulated as a major determinant of the differing interprovincial rates.
Age Factors↗
Diagnostic ultrasound: determination of fetal biparietal diameters as an index of gestational age.
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Cephalometry↗
Nurse practitioners in primary care. II. Prior attitudes of a rural population.
A household survey in a medically underserviced rural population of south-central Ontario was conducted in early 1971 to ascertain attitudes about nurses as providers of primary care. The population sampled had not been exposed to nurse practitioners or family practice nurses before the survey was concluded. The results demonstrate favourable views about nurses giving services in health maintenance and sickness surveillance situations. Personal primary care rendered in homes was highly acceptable to respondents. Physician services were preferred in worry-inducing situations.
Attitude↗
Membranous subvalvular aortic stenosis in tuberous sclerosis.
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Angiocardiography↗
Effect of valproate dose on formation of hepatotoxic metabolites.
Valproate (VPA) therapy has been associated with a rare but fatal hepatotoxicity. 4-ene-VPA and 2(E),4-diene-VPA, unsaturated metabolites of VPA, are hepatotoxins several times more potent than VPA. In a previous study, a dose-dependent excretion of hepatotoxic metabolites was noted in patients receiving VPA. Our study was designed to evaluate the effect of dose on VPA metabolism under controlled conditions. Nineteen healthy volunteers sequentially received three different daily doses of VPA (250, 500, and 1,000 mg). Each dose was given twice daily for 4 days. Urine was collected for one dosage interval (12 h) at steady state for each dose and assayed for 15 VPA metabolites by gas chromatography/mass spectrometry (GCMS). Blood samples were also obtained from eight of the subjects, and VPA was assayed by GCMS. No effect of dose was noted on total plasma clearance. There was a significant dose-dependent decrease in intrinsic hepatic clearance. The intrinsic formation clearance (Clf) of the 4-ene-VPA pathway showed a statistically significant dose-dependent increase (0.22, 0.33, 0.40 ml/h/kg). The corresponding percentage of dose recovered as 4-ene-VPA and its sequential metabolites showed significant dose-dependent increases (0.15, 0.27, 0.62%). The role of VPA dose in the pathogenesis of hepatotoxicity may be more important than was previously believed.
Adult↗
Stiripentol in atypical absence seizures in children: an open trial.
Stiripentol (STP) was added to the antiepileptic drug (AED) regimen of 10 patients with uncontrolled atypical absence seizures (more than one seizure a day). Seven boys and three girls aged 6-16 years participated in the study. Concomitant AEDs included various combinations of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA). Parents counted daily seizures over a 4-week baseline period before institution of STP, and in a 20-week period during STP therapy. To compensate for drug interactions, doses of other AEDs were adjusted during STP administration to keep serum levels close to levels of the baseline period. Maintenance doses of STP were 1,000-3,000 mg/day, giving serum levels of 4-22 micrograms/mL. All patients experienced a decrease in atypical absence seizures. Average decrease was 70% (range 5-95%). Side effects experienced by some patients were dose related and included anorexia, nausea, vomiting, and lethargy. In only 1 patient did an adverse effect (vomiting) require discontinuation of STP. We conclude that STP shows promise in treatment of atypical absence seizures in children, and further trials are warranted.
Adolescent↗
Lorazepam-valproate interaction: studies in normal subjects and isolated perfused rat liver.
Valproate (VPA) has been shown to interact with all the major antiepileptic drugs (AEDs) through two mechanisms of action: displacement from albumin binding sites and inhibition of drug metabolism. More recently, evidence showed that VPA inhibits the elimination of drugs metabolized by glucuronide conjugation. Lorazepam (LZP), which is primarily eliminated by conjugation with glucuronic acid, is administered concurrently with VPA both in treatment of epilepsy and in patients treated with VPA for psychiatric disorders. Therefore, a significant drug interaction is likely. We investigated such interaction both in in vitro isolated perfused rat liver (IPRL) and in normal subjects. LZP [2 mg, intravenous (i.v.) bolus] was administered to 8 normal volunteers before and after chronic dosing with VPA. In 6 of 8 subjects, VPA significantly decreased LZP plasma clearance by an average of 40% (p < 0.05) and increased LZP concentrations by decreasing formation clearance of the LZP glucuronide. In the IPRL studies, VPA also significantly decreased formation of LZP glucuronide (from 0.72 +/- 0.14 to 0.22 +/- 0.15 ml/h/kg, p < 0.05), indicating that IPRL is a useful tool for evaluation of the effect of VPA on drugs eliminated by glucuronide conjugation.
Adult↗
Stability of an extemporaneously compounded cisapride suspension.
The purpose of the study was to formulate a cisapride suspension that would be stable under usual storage conditions for 3 weeks. Cisapride is a new prokinetic agent that is available as a coated tablet; occasionally, however, patients require a liquid preparation of cisapride. Cisapride was formulated with propylene glycol to enhance its solubility. The suspension was buffered with sodium bicarbonate to produce a pH between 6.5 and 7.5. The formulation provided a cisapride suspension that was stable at room temperature for 3 weeks.
Antioxidants↗
Cytochrome P450 3A4 activity in premenopausal and postmenopausal women, based on 6-beta-hydroxycortisol:cortisol ratios.
STUDY OBJECTIVE: To characterize cytochrome P450 (CYP) 3A4 activity in premenopausal and postmenopausal women by evaluating the urinary 6-beta-hydroxycortisol:cortisol ratio. DESIGN: Prospective study SUBJECTS: Thirteen premenopausal and 13 postmenopausal women who were healthy and not receiving drugs known to affect CYP3A4 activity INTERVENTIONS: Beginning on day 2 of menses, premenopausal women collected first morning urine samples every other day for a complete menstrual cycle. Postmenopausal women collected first morning urine every other day for 28 days. MEASUREMENTS AND MAIN RESULTS: Mean weekly 6-beta-hydroxycortisol:cortisol ratios did not differ during the phase (week) of the menstrual cycle. Daily ratios did not differ in postmenopausal women. No difference between premenopausal and postmenopausal women was found on comparing overall median ratios. CONCLUSION: Cytochrome P450 3A4 activity as measured by 6-beta-hydroxy cortisol:cortisol ratio did not differ by week of menstrual cycle, suggesting no menstrual cycle-related changes. Menopause does not appear to be associated with differences in CYP3A4 activity, compared with premenopause.
Adult↗