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Biomedical subjects

S L Gray

Publications and source records attributed to S L Gray.

At least 37 records · Page 2Linked to original sources

Depression, cognitive impairment, and understanding of medication directions in hospitalized elderly patients.

PURPOSE: The objectives of this study were 1) to assess understanding of medication directions of drug therapy in a group of hospitalized elderly who were not receiving assistance with medication administration; and 2) to determine whether depression, cognitive impairment, age, and other characteristics are associated with patient understanding of medication directions. METHODS: The sample consisted of 117 hospitalized elderly patients aged 70 years and older who were taking two or more medications prior to hospitalization and reported medication self-administration. Data collection included demographic characteristics, mood, cognition, and pre-admission medication use and knowledge. RESULTS: Thirteen (11%) patients did not understand directions for two or more pre-admission medications. Being 80 years or older was associated with not understanding medication directions (OR = 6.2, p = .017). There was a trend for depressive symptoms to be associated with not understanding medication directions, however, this was not significant (OR = 3.9, p = .058). CONCLUSIONS: Although all individuals should be assessed for comprehension of their medication regimens, those over 80 years of age with depressive symptoms deserve increased attention. Alternative strategies may need to be developed to improve medication knowledge in the older, depressed hospitalized patient.

Aged↗

Effect of a single dose of diazepam on balance measures in older people.

OBJECTIVE: This study examines the effect of a single dose of diazepam on a spectrum of balance measures in healthy older subjects. The measures include static (postural sway), dynamic (anterior tibialis muscle activation latency), and a complex self-initiated task of balance (functional reach) in addition to neuropsychological tests of attention. DESIGN: A double-blind, two-period, cross-over trial. SETTING: The community surrounding a university hospital. PARTICIPANTS: Community-dwelling, nonsmoking volunteers 65 years of age and older. MEASUREMENTS: Measures included response to unexpected perturbation (platform/EMG muscle latency), self-initiated perturbation (functional reach), and a static measure of balance (postural sway). Neurocognitive tests (digital symbol substitution test, card sorting) were included to document the cognitive effect. RESULTS: Twelve nonsmoking healthy subjects (average age = 70.4 years (66-76 years)) participated. The anterior tibalis muscle latency increased in response to a sudden perturbation with diazepam compared with placebo (TA latency 149 ms vs 142 ms, P < .001). Neurocognitive tests were adversely affected for 90 minutes after diazepam administration compared with placebo (P < .05). Other measures did not demonstrate significant effect of diazepam. CONCLUSIONS: This is among the first reports showing that benzodiazepines affect neuromuscular processing related to balance control. Increased muscle latency to sudden perturbations may represent an effect of diazepam upon the oligosynaptic spinal reflex distinct from the sedation. Surface electromyography may be a valuable noninvasive tool for future studies of drug effect on balance and falls risk among older people.

Aged↗

Characteristics predicting incorrect metered-dose inhaler technique in older subjects.

OBJECTIVE: To determine whether cognitive status, hand strength, and demographic variables are predictive of correct use of metered-dose inhalers by older subjects. METHODS: Clinic patients (n = 29) and healthy volunteers (n = 42) older than 50 years with no previous or limited metered-dose inhaler use were enrolled. After cognitive (Mini-Mental State Examination) and hand strength assessments, subjects received extensive instruction in proper metered-dose inhaler technique. Technique was independently assessed by two evaluators immediately after instruction and 1 week later. Correct technique was defined as (1) activating the canister in the first half of inhalation, (2) continuing to inhale slowly and deeply, and (3) holding breath at full inspiration (5 seconds). Data for the two subject groups were pooled for analyses. RESULTS: The mean age of the subjects was 69.7 years. Forty subjects (56%) demonstrated correct metered-dose inhaler technique at 1 week. Logistic regression showed that hand strength measurement (odds ratio, 0.68; 95% confidence interval, 0.55 to 0.84), Mini-Mental State Examination score less than 24 (odds ratio, 3.66; 95% confidence interval, 1.07 to 12.4), and male gender (odds ratio, 5.01; 95% confidence interval, 1.07 to 23.5) were significant predictors of incorrect inhaler use. Correct use of the metered-dose inhaler was unrelated to age, education, or subject status. CONCLUSIONS: Clinicians should consider cognitive status and hand strength when metered-dose inhaler therapy is initiated for an older adult. Patients with cognitive impairment and hand strength deficits may require more extensive training, frequent follow-up, or alternative dosage forms.

Administration, Intranasal↗

Assessment of interrater and intrarater reliability in the evaluation of metered dose inhaler technique.

STUDY OBJECTIVE: To determine if a training session using videotaped metered dose inhaler (MDI) performances can result in high interrater and intrarater reliability of five evaluators assessing MDI technique. DESIGN: Five evaluators (three pharmacists, two pulmonary fellows) were trained to evaluate MDI technique during a 2-h training session. The training session consisted of verbal instruction and practical experience in evaluating MDI technique using video-taped MDI performances of six nonstudy subjects. After the training session, the evaluators independently observed the same videotaped MDI demonstrations of 14 subjects on two occasions separated by a 7- to 10-day interval. Interrater and intrarater reliability was determined for individual steps by calculating percent agreement and intraclass correlation (ICC) coefficient. RESULTS: Interrater. The interrater reliability for individual steps ranged from 29 to 86 percent (ICC coefficient = 0.13 to 0.81). Steps in which evaluators were in agreement for less than 9 of the 14 subjects were shaking the inhaler before inhalation, exhaling, continuing to inhale slowly, and adequate breath hold. Intrarater: The overall percent agreement by step ranged from 74 to 97 percent. Exhaling to functional residual volume (76 percent) and continuing to inhale slowly and deeply (74 percent) had the lowest overall agreement between the first and second observation day. The consistency of evaluating a step between the two observation days varied considerably depending on the step and evaluator. CONCLUSIONS: High interrater and intrarater reliability in MDI evaluation is difficult to obtain. Clinicians and researchers involved in MDI evaluation and education should be trained to achieve consistency. A single training session using videotaped MDI demonstrations was not adequate in achieving consistency among evaluators. To improve accuracy of research results, researchers should include at least two evaluators to assess MDI technique or take other measures to show and report reliability.

Administration, Inhalation↗

Management of older adults with hypercholesterolaemia.

Although the strength of total cholesterol levels as a relative risk factor for coronary heart disease (CHD) declines with age, the prevalence of CHD increases dramatically with age. Data from cholesterol treatment trials, although sparse in older adults, suggest that dyslipidaemia treatment has the potential to prevent CHD. In particular, dyslipidaemia treatment appears to be most beneficial in older adults with a history of CHD or who have several other CHD risk factors. Dyslipidaemia screening should be selective in the elderly, reserved for those whose health status would be amenable to nutritional or pharmacological therapy, and in whom several CHD risk factors or a history of CHD are present. Since high density lipoprotein cholesterol (HDL) levels retain their inverse association CHD in old age, cholesterol subfractions should be measured in persons being screened in order to adequately assess the severity of dyslipidaemia. Treatment decisions should be guided by the patient's dyslipidaemic class, which is determined by the cholesterol subfractions and serum triglycerides (TG). As in younger persons, nutritional therapy remains the first step in dyslipidaemia management in high risk, nondebilitated older adults. An array of cholesterol modifying medications are available which vary widely in treatment effects, adverse effects and cost. Extra care needs to be taken in prescribing these agents in older adults because of greater potential for adverse effects and interactions with other medications. The cost-effectiveness of pharmacological treatment decreases with age and increases with the severity of dyslipidaemia, a history of CHD, or the presence of multiple CHD risk factors. When comparing elderly to middle-aged adults, the relative cost-effectiveness of different cholesterol-lowering medications may be altered due to age-related changes in therapeutic efficacy and adverse effects.

Aged↗

Measured versus estimated creatinine clearance in a high-functioning elderly sample: MacArthur Foundation Study of Successful Aging.

OBJECTIVE: To assess the validity of several equations for estimating creatinine clearance in a large sample of high-functioning, community-dwelling elderly. DESIGN: Serum and 12-hour urine samples were collected and assayed for creatinine using the Jaffe total chromagen method. Fifteen clearance-estimating equations were evaluated for bias, accuracy, correlation with measured clearance values, and frequency of erroneous placement into renal function categories. Stepwise regression modeling and reliability testing were performed on a split sample to construct and assess a novel creatinine-clearance-estimating equation. SETTING: New Haven, Connecticut, East Boston, Massachusetts, and a five-county region in and around Durham, North Carolina. PARTICIPANTS: A subsample of community-dwelling men and women (age range 70-79 years) from the Established Populations for Epidemiological Studies of the Elderly was screened for physical and cognitive functioning and placed into high-, medium-, and low-functioning groups (n = 1354). High-functioning respondents who provided blood and complete urine samples (n = 762) were included in the present study. RESULTS: In general, estimated creatinine clearance was more closely correlated to measured values in males than in females. Most equations underestimated creatinine clearance, with average bias ranging from -33.1 mL/min to +19.6 mL/min. Predictive accuracy ranged from 18.2 mL/min to 38.0 mL/min. Equations were variable in their erroneous placement of individuals into renal function categories. Regression modeling yielded an equation which contained novel components but failed to provide better estimates of creatinine clearance than those already available. CONCLUSIONS: The equations evaluated here provide unacceptable predictions of creatinine clearance in normally aging individuals. We advocate the use of serum drug concentration measurements when available and encourage investigation into timed urine collections of short duration as alternatives to clearance-estimating equations in the elderly.

Activities of Daily Living↗

Secretory patterns of growth hormone and insulin-like growth factor-I during peripubertal period in intact and castrate male cattle.

Fifteen Angus bulls and 15 Angus steers 9 months of age and 275 kg of body weight were bled at 20-min intervals over a 6-hr period and serum GH and IGF-I concentrations were measured by RIA. There were no differences between bulls and steers in the mean GH concentration, pulse frequency and amplitude when analyzed by the computer program PULSAR. Mean IGF-I concentration was not different between the two sex phenotypes, nor was there a significant correlation between the integrated IGF-I and GH concentrations. Subsequently, five bulls and five steers were selected from the 30 animals, full-fed a diet for growth in individual pens for 3 months and bled at 15-min intervals over a 24-hr period. Bulls tended to show a greater weight gain and feed conversion efficiency (P less than .10) than steers during the 3-month period. Serum GH concentrations had a pulsatile pattern in all animals with no apparent diurnal rhythm during the 24-hr bleeding. Although mean GH concentration was not different between the two sex phenotypes, bulls tended to have lower baseline levels (P less than .10) and greater peak amplitudes than steers. Serum IGF-I concentrations fluctuated within a two-fold concentration range, with no obvious pulsatility similar to that of GH. Mean IGF-I concentrations of each of the 10 animals were correlated with mean peak GH amplitudes (r = .79), but not with mean GH. These results suggest that gonadal hormone(s) modulates the GH secretory pattern and increases IGF-I secretion which may be related to the greater growth rate of bulls compared with steers.

Age Factors↗

Effect of holding time and temperature of bovine whole blood on concentration of progesterone, estradiol-17beta and estrone in plasma and serum samples.

Bovine jugular venous blood was collected, with and without heparin, and aliquoted into 140 12-ml tubes. Four subsamples (two heparinized and two coagulated) were centrifuged immediately (time zero) and plasma or serum was aspirated and stored at -20 degrees C. One-half of the remaining subsamples were stored at 4 degrees C and the other one-half at 25 degrees C (room temperature). At 1-h intervals (0 to 24 h), 6-h intervals (24 to 72 h) and at 96 and 120 h, four subsamples (heparinized and coagulated at both 4 degrees C and 25 degrees C) were centrifuged, plasma or serum was aspirated and stored at -20 degrees C. Whole blood incubation for 1 h at 25 degrees C reduced mean plasma and serum progesterone (P(4)) concentration (P<0.05). Similarly, whole blood incubation at 4 degrees C for 2 and 3 h, respectively, reduced mean plasma and serum P(4) concentration (P<0.05). No difference was found in mean P(4) concentration between plasma and serum samples harvested from whole blood incubated at 4 degrees C or 25 degrees C. Concentration of estradiol-17beta (E(2)) and estrone (E(1)) fluctuated over time, irrespective of holding temperature. There was a blood type, heparinized or coagulated, by time interaction (P<0.01) for both E(2) and E(1) concentrations It was concluded that incubation time and temperature between collection and centrifugation of bovine blood samples influenced the assayable P(4) concentration in both plasma and serum. In contrast, incubation temperature had no effect on assayable E(2) and E(1) concentrations, but assayable E(2) and E(1) over time were differentially affected, depending on whether plasma or serum was assayed.

Journal Article↗

Residue levels of endogenous estrogens in beef tissues.

Endogenous estrogen concentrations in edible tissues of cows, bulls and steers were compared with those of steers with estrogen implants. Concentrations are expressed as pg estrogen/g of tissue, wet weight. In addition, depletion rates of estradiol-17 beta (E2 beta) estrone (E1) and estradiol-17 alpha (E2 alpha) from these tissues and blood plasma were determined. In muscle, the main estrogen was E2 beta, regardless of sexual status (nonpregnant cow, bull or steer); however, concentrations approached the lower limits of analytical sensitivity. In liver and kidney, E2 beta and E1 were equimolar (25 to 40 pg/g for each) in heifers and steers, whereas in kidney fat, concentrations of E1 exceeded those of E2 beta. Concentrations of E1 in fat were slightly higher in bulls than in cows or steers. The predominant estrogen in fat during pregnancy was E1, with concentrations 150 times greater than those of nonpregnant heifers or nonimplanted steers and 75 times the concentration found in steers with E2 beta implants. In kidney of pregnant cows, E1 rose 40-fold and in liver 10-fold over that of implanted steers. Concentrations of E2 alpha were low and depleted rapidly after withdrawal of an E2 beta implant. Tissue depletion studies of the three estrogens demonstrated that E1 disappeared from plasma, fat, liver and kidney more slowly than E2 beta or E2 alpha. Depletion of E2 beta from the tissue can be manipulated as shown by the faster rate of depletion in implanted steers than in nonimplanted steers. Because E1 is cleared from fat more slowly than E2, and E1 concentrations are higher, this estrogen-tissue combination should be used to monitor estrogen implants as anabolic agents.

Animals↗

Studies on the stimulation of dolichol-mediated glycosylation by dexamethasone in HeLa cells.

The effect of the addition of 1 microM-dexamethasone on the temporal sequence of the glycosylation process has been studied in HeLa S3G cells. In the presence of delipidized serum, dexamethasone caused an increase in 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and an accelerated synthesis of dolichols. These events were followed by an increase in the transfer of mannose from GDP-mannose to mannolipid. An increase in the rate of synthesis of lipid-linked oligosaccharides and a stimulation of glycosylation were observed in cells grown in the presence of delipidized serum in the culture medium. The data are consistent with the view that cellular syntheses of lipids and glycoproteins are co-ordinately controlled.

Acetates↗

Evidence for the stimulation of dolichol and mannolipid synthesis by glucocorticoids in HeLa cells.

The effects of addition of 1 microM-dexamethasone on the rate of transfer of mannose from GDP-mannose into mannolipid have been studied in HeLa cell cultures. Concurrent with an increase in incorporation of mannose into glycoproteins, the incorporation of mannose from GDP-mannose in vitro into mannolipid and dolichol-linked oligosaccharides was increased after dexamethasone treatment. Stimulation of mannolipid synthesis showed a correlation with the 11 beta, 17 alpha, 21-trihydroxy structure of C21 steroids. Dexamethasone treatment also resulted in an increased incorporation of acetate into dolichol and dolichyl phosphate. The results suggest that the effect of dexamethasone on the cell-surface glycoprotein accumulation is related to increased sugar-linked dolichol synthesis.

Acetates↗

Corticosteroids and phosphatidylcholine biosynthesis in microsomal fractions from L5178Y lymphoma.

Microsomal fractions from mouse lymphoma L5178Y and from rat thymocytes were used to follow incorporation of radiolabel from cytidine diphosphate-[methyl-14C]choline into microsomal lipids. Dexamethasone, at concentrations ranging from 2.8 X 10(-6)M to 2.8 X 10(-5)M, partially inhibited this transfer reaction. Microsomes prepared from freshly isolated thymocytes were more sensitive to the effects of dexamethasone showing inhibition at concentrations of steroid as low as 2.8 X 10(-8)M. The inhibitory effect did not depend on the amount of the available endogenous diglycerides and was not related to a possible stimulation of cytidine diphosphate choline transferase back reaction by the steroid. The survey of a broad selection of different steroids revealed a lack of correlation between the known lymphocytolytic properties of steroids and their effects on cytidine diphosphate choline transferase. Dexamethasone was the only steroid of the glucocorticoid group that inhibited this reaction in microsomal fractions of L5178Y lymphoma. The structural requirement for the inhibitory effect was related to the absence of oxygen functions in positions 11 and 17 of the steroid and, possibly, to the presence of both C-20 and C-21 on the side chain.

Adrenal Cortex Hormones↗