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Biomedical subjects

P R Montgomery

Publications and source records attributed to P R Montgomery.

At least 19 recordsLinked to original sources
PubMed2001

Risk factors for Alzheimer's disease: a population-based, longitudinal study in Manitoba, Canada.

BACKGROUND: Current knowledge of risk factors for Alzheimer's disease (AD) is limited. Data from a longitudinal, population-based study of dementia in Manitoba, Canada were used to investigate risk factors for AD. METHODS: Cognitively intact subjects completed a risk factor questionnaire assessing sociodemographic, genetic, environmental, medical and lifestyle exposures. Five years later, 36 subjects had developed AD and 658 remained cognitively intact. RESULTS: Older subjects or those who had fewer years of education were at greater risk of AD. After adjusting for age, education and sex, occupational exposure to fumigants/ defoliants was a significant risk factor for AD (relative risk [RR] = 4.35; 95% CI : 1.05--17.90). A history of migraines increased the risk of AD (RR = 3.49; 95% CI : 1.39--8.77); an even stronger effect was noted among women. Self-reported memory loss at baseline was associated with subsequent development of AD (RR = 5.15; 95% CI : 2.36--11.27). Vaccinations and occupational exposure to excessive noise reduced the risk of AD. CONCLUSIONS: Some well-known risk factors for AD were confirmed in this study and potential new risk factors were identified. The association of AD with a history of migraines and occupational exposure to defoliants/fumigants is of particular interest because these are biologically plausible risk factors.

Aged↗
PubMed1996

Bioavailability and pharmacokinetic disposition of tacrine in elderly patients with Alzheimer's disease.

The pharmacokinetic disposition of intravenous and oral doses of tacrine was determined in 5 elderly patients (aged 64 to 96 y) with the clinical diagnosis of Alzheimer's disease. The bioavailability of the oral formulation was low (9.9% to 36.4%), and the plasma half-life was not altered by route of drug delivery. These data indicate that tacrine elimination occurs by a 1st-order process. Plasma clearance of tacrine varied more than its half-life, which is consistent with a modulating effect of apparent volume of distribution (Vd). Our findings, together with other limited published studies, suggest that use of tacrine for the treatment of Alzheimer's disease (AD) will be confounded by the high interindividual variability in its kinetic disposition.

Aged↗
PubMed1994

Impact of a formulary on personal care homes in Manitoba.

OBJECTIVE: To assess the impact of a formulary on drug expenditures and prescribing trends in personal care homes (nursing homes). DESIGN: Quasi-experimental analysis of a drug prescription database before and after implementation of the formulary. SETTING: Personal care homes in Manitoba. PATIENTS: Residents occupying the 6848 beds of the 88 personal care homes that did not already have a formulary. INTERVENTION: Formulary, introduced Apr. 1, 1987. MAIN OUTCOME MEASURES: Drug expenditures from Apr. 1, 1985, to Mar. 31, 1990; proportion of residents receiving a prescription by drug class and rate of prescriptions of nonformulary drugs in the year before and 2 years after the formulary was introduced. MAIN RESULTS: The total drug expenditures per bed remained constant during the first year after the formulary was implemented, even though the annual drug inflation rate was 9.8% on average during the study period. Expenditures 2 and 3 years after implementation rose by 9.4% and 5.8% respectively. Those for specific agents and drug classes targeted as being inappropriate for long-term care decreased greatly because of reduced prescribing. Expenditures for some other drug classes increased mainly because newer, more expensive agents were used. The mean drug expenditure per bed varied widely between homes; neither size nor location were found to correlate with drug expenditure, but adherence to the formulary did predict personal care homes with decreased expenditures. CONCLUSIONS: A formulary in personal care homes can improve therapeutic management. The impact on cost containment was not as strong after the first year, although expenditures remained less than the rate of inflation for drug costs.

Aged↗
PubMed1991

Prescribing patterns for older heavy drug users living in the community.

We report an analysis of prescription drugs claimed under a government-sponsored, universal Pharmacare program for community-dwelling adults aged greater than or equal to 50 years in Manitoba during 1975, 1978, 1981, and 1984. We limited our analysis to claimants who reported over six drugs in a year in order to control for effects of inflation and a changing deductible. The median number of prescribed drugs and the percent of claimants over age 50 years receiving prescriptions from multiple physicians decreased during the course of our study. In this sample of heavy drug users, age and sex did not consistently correlate with overall drug use, although there was correlation for specific drug groups. The relative ranking of prescribed drugs changed over the years, although benzodiazepines, thiazide diuretics, topical steroids, and codeine-containing analgesics remained near the top. Barbiturates and topical antibiotics showed the greatest drop in prescription rates; acetaminophen and beta-blockers increased the most. Using these community data, we project the prevalence of drug-related adverse events to be highest with beta-blockers, nonsteroidal antiinflammatory drugs, thiazide diuretics, and benzodiazepines.

Age Factors↗
PubMed1988

Drug-associated hospital admissions in older medical patients.

A survey of drug-related admissions of patients aged 50 years and older was conducted at the Health Sciences Centre, Winnipeg to determine the interrelationship of risk factors, and isolate the effect of age. All nonelective medical admissions were prospectively assessed to determine the role of drug therapy as a contributory factor. Of the 863 eligible admissions, 162 exhibited at least one drug-related adverse patient event (DRAPE) at the time of hospitalization. This accounted for 19% of the admissions (23% of 718 admissions that involved prescription drugs). Although adverse drug reactions were responsible for many DRAPEs (48%), intentional noncompliance (27%), treatment failure (19%), alcohol (14%), and medication error (10%) were also frequent contributing causes. Drugs commonly implicated in DRAPEs were systemic steroids, digoxin, nonsteroidal anti-inflammatory agents, alpha-methyldopa, calcium channel blockers, beta-blockers, theophylline, furosemide, sympathomimetics, thiazides, and benzodiazepines. The risk of a DRAPE was related to the number of diseases prior to admission (r = 0.81; P less than .026) and the number of drugs used (r = 0.77; P less than .001). Age was not correlated with the risk of a DRAPE. Females had significantly more adverse drug reactions, although sex was not a predictor for overall DRAPE risk.

Aged↗
PubMed1988

Hepatic uptake of indocyanine green and perfusion rate in rats: effect of age and albumin concentration.

Liver blood flow and hepatic uptake of some indicator substances have been reported to fall with age in both rats and humans. We used an isolated liver system, which was perfused in one pass with hemoglobin free buffer, to investigate the effect of albumin concentration, buffer flow rate, and age upon hepatic clearance of the dye, indocyanine green. We measured the half-life of a bolus of indocyanine green given intravenously to male Sprague-Dawley rats aged 10 and 24 months and then examined its clearance in vitro using their isolated perfused livers. After perfusion, the livers were homogenized and separated into subcellular fractions. The mean liver weight declined significantly (young, 19.7 +/- 2.9 g vs. old, 13.9 +/- 2.6 g; p less than 0.02). In vivo the indocyanine green clearance was reduced in the aged rats (3.2 +/- 1.0 vs. 5.1 +/- 1.7 mL/min; p less than 0.05). In the isolated perfused liver system, extraction ratio showed an inverse curvilinear correlation with albumin concentration and buffer flow rate, but did not differ with age. Hepatic protein content and dye subcellular localization did not differ between the two groups. In conclusion, the fall in indocyanine green clearance in vivo is not paralleled by the ability of the organs to extract the dye in vitro, and likely reflects a decline in hepatic mass and blood flow.

Aging↗
PubMed1987

Enprofylline disposition in the presence and absence of amoxycillin or erythromycin.

1 The kinetic disposition of a novel xanthine bronchodilator, enprofylline, was determined in young healthy male volunteers in the presence and absence of amoxycillin or erythromycin. These data were compared to those derived from a similar study of theophylline disposition in the presence and absence of erythromycin. 2 Erythromycin inhibited theophylline disposition only in those subjects in whom the control kinetic study was done after antibiotic ingestion, but the effect was modest. Erythromycin had no effect on enprofylline disposition. 3 Amoxycillin reduced the renal clearance of enprofylline, but the change was not statistically significant.

Adult↗
PubMed1986

Salicylate metabolism: effects of age and sex in adults.

The plasma concentrations and urinary excretion rates of salicylic acid (SA) and some of its metabolites (salicyluric acid [SUA] and acyl and phenolic glucuronide conjugates) were measured after an oral dose of acetylsalicylic acid to 44 healthy subjects of both sexes 20 to 78 years old. There was no change in the SA absorption rate, and plasma clearance of SA was not affected by age or sex. The volume of distribution increased with age in men but not in women. Plasma concentrations of SUA rose with age as the renal clearance of this metabolite fell. The kinetic parameters Km and Vmax for the SA-to-SUA reaction did not change with age; Vmax was significantly higher in women than in men. Urinary recovery of SA and its metabolites essentially accounted for the administered dose, and was little influenced by age or sex. We conclude that these factors play a minor role in the disposition of salicylate.

Administration, Oral↗
PubMed1983

Synaptic junctions isolated from cerebellum and forebrain: comparisons of morphological and molecular properties.

Synaptic junction (SJ) fractions have been isolated from rat cerebellum which are similar to forebrain SJs on the basis of morphology and enrichment of synaptic structures. The polypeptide compositions of SJ fractions were analyzed by one- and two-dimensional SDS-gel electrophoresis and stained by the silver technique. Equivalent numbers of proteins that possess similar relative mobilities (Mr), isoelectric points and staining intensities were present in cerebellum and forebrain synaptic fractions. A few prominent differences were observed between cerebellum and forebrain synaptic fractions; cerebellum SJs contained a 240 K protein that was not detected in the forebrain and the 52,000 K, major PSDp protein was present in forebrain SJs in amounts that are approximately 5-fold greater than in cerebellum SJ fractions. The identity of the cerebellum mPSDp was verified by electrophoretic mobility, peptide fingerprinting and [125I]calmodulin binding. Differences between various synaptic fractions in mannose containing glycoproteins were examined by the binding of [125I]concanavalin A (Con A) to gels. On the basis of apparent molecular weights, the glycoproteins in forebrain and cerebellum SPMs were very similar. In contrast, however, the prominent glycoproteins that reside in the postsynaptic junctional membrane of forebrain SJs were undetectable in SJ fractions isolated from cerebellum. SJ fractions from cerebellum contained their own distinct group of Con A binding glycoproteins. SPM and SJ fractions from forebrain and cerebellum were examined for receptors for excitatory (aspartate, glutamate and kainic acid) and inhibitory (GABA) neurotransmitters and the benzodiazepine analog flunitrazepam. On the basis of relative receptor contents, SJ fractions isolated from either brain region were qualitatively similar and bound significant amounts of excitatory and inhibitory transmitters. These findings support the notion that SJs from cerebellum contain a distinct class of synaptic elements that are in large part derived from asymmetric, type I synapses.

Animals↗
PubMed1982

Subcellular localization of the 52,000 molecular weight major postsynaptic density protein.

We have recently reported that in isolated synaptic junctions, the quantity of the major post-synaptic density protein (mPSDp, Mr = 52,000) increases approximately twenty-fold during the third and fourth weeks of postnatal development. In the study that follows, systematic analyses were carried out to determine the subcellular localization of this prominent synaptic protein in adult brain and non-neuronal tissues. Subcellular fractionation and SDS-gel electrophoresis were used to isolate various tissue components and identify proteins that possessed molecular weights similar to that of the mPSDp. To unambiguously verify the molecular identity of all proteins suspected of being the mPSDp, two-dimensional peptide fingerprinting was carried out. In addition, the different subcellular fractions were examined for the presence of structures morphologically resembling the postsynaptic density. The mPSDp was found only in fractions containing identifiable asymmetric synaptic structures and/or postsynaptic densities. This protein was not found in non-neuronal tissues or any other fraction in which there was not a demonstrable presence of postsynaptic densities. This work strongly indicates that the major PSD protein is a molecular 'marker' specific to asymmetric synapses in the mammalian forebrain.

Animals↗
PubMed1981

Increased serum salicylate metabolites with age in patients receiving chronic acetylsalicylic acid therapy.

A high pressure liquid chromatographic method was used to measure the serum concentrations of salicylic, salicyluric and gentisic acids in patients receiving chronic acetylsalicylic acid therapy. There was good correlation between this method and the established colorimetric assay for salicylic acid. The concentration of gentisic and salicyluric acids were increased in patients older than 60 years. No correlation was found with sex, concomitant ingestion of other drugs, serum creatinine or serum albumin.

Adult↗