In defense of genomics.
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Alzheimer Disease↗
Biomedical subjects
T Harris
Publications and source records attributed to T Harris.
When the hospice patient is manipulative.
Oncology and hospice literature have addressed the problem of psychiatric complications, secondary to the stressors of diagnosis and treatment. This literature focuses particularly on depression and anxiety, which not only compound patients' suffering but also may interfere with optimal care. Little attention has been given, however, to the unique challenges of providing hospice care to patients with preexisting psychiatric conditions. As hospice care becomes increasingly mainstream in the health care system, we can expect to meet more patients with such conditions. In order to contribute to collegial dialogue that addresses this minority population in hospice services, a case study is presented in this article of the process of care for a hospice patient with a preexisting psychiatric condition. Interventions are suggested, using a theoretical matrix of hospice philosophy and principles of care for manipulative patients.
Adaptation, Psychological↗
Effects of age on body fat distribution and cardiovascular risk factors in women.
We conducted a cross-sectional study of body fat distribution and metabolic variables and the interrelations among these factors in 134 women aged 18-71.9 y. Body fat distribution was measured with use of computerized tomography. A significant positive correlation was observed between age and visceral adipose tissue (VAT) and between VAT and body weight. When subjects were divided into five age groups, VAT values were significantly higher in older groups. Values for triacylglycerols, cholesterol, fasting glucose, 2-h glucose, and the sum of glucose values during an oral-glucose-tolerance test were significantly higher in older subjects. After adjustment for visceral fat, no significant differences in any metabolic variable studied, except cholesterol, were found across the five age groups. In conclusion, we found that regional body fat distribution in older women was different from that in younger subjects: older women had larger amounts o visceral fat. Values for metabolic variables were also higher in older subjects. Our data suggest that redistribution of body fat in older subjects is associated with changes in metabolic variables.
Adipose Tissue↗
Correlates of performance-based measures of muscle function in the elderly: the Cardiovascular Health Study.
BACKGROUND: It is unknown how much age-related changes in muscle performance represent normal aging versus the effects of chronic disease and life style. We examined the correlates of four performance measures-gait speed, timed chair stands (TCS), grip strength, and maximal inspiratory pressure (MIP)-using baseline data from the Cardiovascular Health Study (CHS), a population-based study of risk factors for heart disease and stroke in persons > or = age 65. METHODS: We analyzed data from the 5,201 CHS participants. Variables were arranged into nine categories: Personal Characteristics, Anthropometry, Physical Condition, Reported Functional Status, Subjective Health, Psychological Factors, Symptoms, Cognitive Status, Habits and Lifestyle, and Prevalent Disease. Independent correlates were identified using stepwise linear regression. RESULTS: The regression models explained 17.7-25.4% of the observed variability. Although age significantly correlated with each measure, it explained little of the variability (< or = 5.7%). Anthropometric features plus physical condition explained 14.0-17.4% of the variability for grip strength and MIP, but 2.8-12.9% of the variability for gait speed and the log of TCS. Subjective health and psychological factors explained 1.8-9.4% of the variability in gait speed and the log of TCS, but < or = 1.2% of the variability in grip strength and MIP. Variables for prevalent disease explained < or = 1.3% of the variability in each measure. CONCLUSIONS: After age 64, age explained little of the variability in muscle performance in a large sample of mostly functionally intact, community-dwelling older persons. Complex measures such as gait speed were more associated with subjective factors than were direct measures of strength. Prevalent disease contributed surprisingly little to muscle performance.
Aging↗
The association of plasma IL-6 levels with functional disability in community-dwelling elderly.
BACKGROUND: IL-6 is a multifunctional cytokine that has been shown to increase with age. METHODS: Plasma IL-6 was measured by ELISA in 1,727 community-dwelling elderly subjects whose blood was drawn during the third in-person survey of the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). Demographics, functional status (disability), and disease states were determined. Correlations of these factors with IL-6 were analyzed with Spearman's Rho while differences between groups were assessed by Wilcoxon test. RESULTS: IL-6 levels were higher with age (p = .0001) even in this older population (> 70 years). There was a positive correlation between IL-6 and functional disability for each of the functional status measures (p = .0001), as well as a correlation between self-rated health and IL-6. Significantly higher median levels of IL-6 were found in subjects reporting prevalent cancer, heart attack, and high blood pressure, but not diabetes or arthritis. The association between age and functional status with high IL-6 remained when all other variables were controlled, in multivariable analysis. CONCLUSIONS: This association between increased plasma IL-6 levels and functional status suggests that dysregulation of IL-6 may be related to the functional disability seen with aging, and that IL-6 may be useful as a component of an overall marker of health.
Aged↗
Muscle mass and strength: relation to function in population studies.
The use of the term sarcopenia to describe the age-related loss in skeletal muscle and its functional consequences is relatively recent. However, interest in the relationship of muscle mass to strength and function predates the concept of sarcopenia as researchers have attempted to understand differences in mass and strength between men and women, young and old. Most of these studies are cross-sectional comparisons in which muscle mass and strength tend to be linearly related, so that those with more muscle tend to be stronger. This article focuses instead on some potential problems with the sarcopenia-function association in old age and presents what little data exist from longitudinal population studies addressing the effect of sarcopenia over time.
Aged↗
Appendicular skeletal muscle mass: effects of age, gender, and ethnicity.
This study tested the hypothesis that skeletal muscle mass is reduced in elderly women and men after adjustment first for stature and body weight. The hypothesis was evaluated by estimating appendicular skeletal muscle mass with dual-energy X-ray absorptiometry in a healthy adult cohort. A second purpose was to test the hypothesis that whole body 40K counting-derived total body potassium (TBK) is a reliable indirect measure of skeletal muscle mass. The independent effects on both appendicular skeletal muscle and TBK of gender (n = 148 women and 136 men) and ethnicity (n = 152 African-Americans and 132 Caucasians) were also explored. Main findings were 1) for both appendicular skeletal muscle mass (total, leg, and arm) and TBK, age was an independent determinant after adjustment first by stepwise multiple regression for stature and weight (multiple regression model r2 = approximately 0.60); absolute decrease with greater age in men was almost double that in women; significantly larger absolute amounts were observed in men and African-Americans after adjustment first for stature, weight, and age; and >80% of within-gender or -ethnic group between-individual component variation was explained by stature, weight, age, gender, and ethnicity differences; and 2) most of between-individual TBK variation could be explained by total appendicular skeletal muscle (r2 = 0.865), whereas age, gender, and ethnicity were small but significant additional covariates (total r2 = 0.903). Our study supports the hypotheses that skeletal muscle is reduced in the elderly and that TBK provides a reasonable indirect assessment of skeletal muscle mass. These findings provide a foundation for investigating skeletal muscle mass in a wide range of health-related conditions.
Absorptiometry, Photon↗
Apolipoprotein E epsilon 2 allele and risk of stroke in the older population.
BACKGROUND AND PURPOSE: There is evidence for a role of apolipoprotein E (apoE) in atherosclerosis. Coronary heart disease morbidity is higher in persons carrying an epsilon 4 allele and lower in those carrying an epsilon 2 allele, but the effect on cerebrovascular disease is controversial. We estimated the risk of stroke associated with different apoE genotypes in older persons. METHODS: At the sixth annual follow-up of the Iowa cohort of the Established Populations for Epidemiologic Studies of the Elderly, 1664 persons aged > or = 71 years and free of stroke were genotyped for apo E. Occurrence of ischemic strokes was prospectively assessed from subsequent hospital discharge records and death certificates. RESULTS: One hundred fifty persons had an ischemic stroke over the subsequent 5 years (21.2 per 1000 person-years). The presence of epsilon 3 and epsilon 4 did not influence stroke risk. Among persons aged < 80 years at the time of genotyping, epsilon 2 carriers had lower risk of incident stroke, while no effect was detected in the older group. Compared with epsilon 2 carriers aged 70 to 79 years (reference group), those in the same age group and not carrying an epsilon 2 had 2.6-fold higher risk of incident stroke, and those aged > or = 80 years had even higher risk of stroke but without any difference according to presence/absence of epsilon 2 (relative risks 3.6 and 3.3). Results remained substantially unchanged when adjusted for potential confounders and in models estimating the effect of apoE polymorphism on the risk of developing a stroke at ages between 70 and 79 years (56 events) and separately at ages > or = 80 years (94 events). CONCLUSIONS: The conditioning influence of age on the protection conferred by the apoE epsilon 2 allele on stroke risk may account for previous controversies. This hypothesis should be verified in a population with a wider age range.
Aged↗
Linkage analyses of schizophrenia to chromosome 6p24-p22: an attempt to replicate.
The present study evaluates evidence for linkage of schizophrenia to chromosome 6p24-p22. An independent sample of 211 families ascertained on the basis of having an affected sib-pair diagnosed with schizophrenia or schizoaffective disorder was assessed with seventeen polymorphic markers spanning a 37cM region. Linkage analysis was performed with parametric and non-parametric methods to test for cosegregation using 4 models of inheritance. Neither two-point nor multipoint non-parametric analyses reached significance at a level less than 0.01 for any markers examined in the region and lod score analyses were not suggestive of linkage. Based on initial findings in the present data set and recently published linkage results, two specific areas were densely covered with markers and tested for linkage disequilibrium. After correcting for multiple comparisons within each locus, no significant deviation from expected allele transmission ratios was observed. The present findings together with the published literature fail to find consistent evidence of a linkage for schizophrenia to a single locus on chromosome 6.
Adult↗
Weight change between age 50 years and old age is associated with risk of hip fracture in white women aged 67 years and older.
BACKGROUND: Although changes in body weight with aging are common, little is known about the effects of weight change on health in old age. OBJECTIVES: To study the effects of weight loss and weight gain from age 50 years to old age on the risk of hip fracture among postmenopausal white women aged 67 years and older and to determine if the level of weight at age 50 years modifies this risk. METHODS: The association between weight change and the risk of hip fracture was studied in 3683 community-dwelling white women aged 67 years and older from three sites of the Established Populations for Epidemiologic Studies of the Elderly. RESULTS: Extreme weight loss (10% or more) beginning at age 50 years was associated in a proportional hazards model with increased risk of hip fracture (relative risk [RR], 2.9; 95% confidence interval [CI], 2.0-4.1). This risk was greatest among women in the lowest (RR, 2.3; CI, 1.1-4.8) and middle (RR, 2.8; CI, 1.5-5.3) tertiles of body mass index at age 50 years. Among the thinnest women, even more modest weight loss (5% to < 10%) was associated with increased risk of hip fracture (RR, 2.3; CI, 1.0-5.2). Weight gain of 10% or more beginning at age 50 years provided borderline protection against the risk of hip fracture (RR, 0.7; CI, 0.4-1.0). The RRs for weight gain of 10% or more were protective only among women in the middle and high tertiles of body mass index at age 50 years and were not significant (middle tertile RR, 0.8; CI, 0.3-1.8; high tertile RR, 0.6; CI, 0.2-1.9). CONCLUSIONS: Weight history is an important determinant of the risk of hip fracture. Weight loss beginning at age 50 years increases the risk of hip fracture in older white women, especially among those who are thin at age 50 years; weight gain of 10% or more decreases the risk of hip fracture. Physicians should include weight history in their assessment of postmenopausal older women for risk of hip fracture.
Age Factors↗
How useful is body mass index for comparison of body fatness across age, sex, and ethnic groups?
This study tested the hypothesis that body mass index (BMI) is representative of body fatness independent of age, sex, and ethnicity. Between 1986 and 1992, the authors studied a total of 202 black and 504 white men and women who resided in or near New York City, were ages 20-94 years, and had BMIs of 18-35 kg/m2. Total body fat, expressed as a percentage of body weight (BF%), was assessed using a four-compartment body composition model that does not rely on assumptions known to be age, sex, or ethnicity dependent. Statistically significant age dependencies were observed in the BF%-BMI relations in all four sex and ethnic groups (p values < 0.05-0.001) with older persons showing a higher BF% compared with younger persons with comparable BMIs. Statistically significant sex effects were also observed in BF%-BMI relations within each ethnic group (p values < 0.001) after controlling first for age. For an equivalent BMI, women have significantly greater amounts of total body fat than do men throughout the entire adult life span. Ethnicity did not significantly influence the BF%-BMI relation after controlling first for age and sex even though both black women and men had longer appendicular bone lengths relative to stature (p values < 0.001 and 0.02, respectively) compared with white women and men. Body mass index alone accounted for 25% of between-individual differences in body fat percentage for the 706 total subjects; adding age and sex as independent variables to the regression model increased the variance (r2) to 67%. These results suggest that BMI is age and sex dependent when used as an indicator of body fatness, but that it is ethnicity independent in black and white adults.
Adipose Tissue↗
Vocational training for general practice in inner London. Is there a dearth? And if so what's to be done?
OBJECTIVE: To identify the nature and extent of any vocational training deficit within the London initiative zone and investigate the reasons. DESIGN: Collation of statistics and postal questionnaire surveys. SETTING: Thames regions inside and outside the London initiative zone. SUBJECTS: General practice registrars, trainers, principals from non-training practices, and vocational training course organisers. MAIN OUTCOME MEASURES: Trends in numbers of general practice registrars, proportions of trainers, views on current vocational training in inner London. RESULTS: Numbers of general practice registrars fell significantly between 1988 and 1993 within the London initiative zone and in England overall. The number of registrars within the zone fell by more than in the rest of the Thames regions, where the decline was not statistically significant. A lower proportion of principals were approved as trainers within the zone than in the rest of the Thames regions and England overall. In their responses to the survey (88% of inner London registrars responded and 81% of outer Thames registrars) registrars suggested that improving remuneration and personal safety would make training in London more attractive. Trainers and non-trainers (response rates 89% and 66% respectively) also suggested increasing remuneration for trainers together with more protected time for training. CONCLUSIONS: Less vocational training takes place within the London initiative zone than in the rest of the Thames regions and England overall, although there are discrepancies in official statistics. As well as specific recommendations for improving recruitment to vocational training in inner London, measures to tackle inner city deprivation should also remain high on the political agenda.
Adult↗
Hepatic overexpression of insulin-like growth factor-II in adulthood increases basal and insulin-stimulated glucose disposal in conscious mice.
The physiological role of circulating insulin-like growth factor-II (IGF-II) in adult humans is poorly understood. We recently generated an IGF-II transgenic murine model of persistent IGF-II production (plasma IGF-II approximately 30-fold increased above normal) through over-expression of the transgene driven by the major urinary protein promoter (Rinderknecht, E., and Humbel, R. E. (1978) J. Biol. Chem. 269, 13779-13784). To determine whether in vivo insulin action is improved in these transgenic mice, we performed euglycemic insulin (18 milliunits/kg.min) clamp studies in conscious IGF-II transgenic and in age- and weight-matched control mice. Plasma glucose and insulin concentrations were significantly lower in the IGF-II transgenic compared with both control grouoff Despite decreased plasma glucose concentration, basal hepatic glucose production (HGP) and glucose clearance were increased. During the insulin clamp studies in IGF-II transgenic mice compared with control mice (a) the rates of glucose infusion and glucose uptake were increased by approximately by 65 and approximately 55%, respectively; (b) glycolysis was increased by approximately 12% while glycogen synthesis was approximately 2-fold higher; (c) while the suppression of plasma free fatty acid was similar, the increment in plasma lactate concentration was significantly higher; (d) although HGP was similarly inhibited by insulin, phosphoenolpyruvate gluconeogenesis was enhanced and accounted for a larger portion of HGP (64% versus approximately 40% in control mice). Our data suggest that the persistence of circulating IGF-II in adult mice to levels commonly observed in adult humans (50-70 nM) causes a marked improvement in peripheral (skeletal muscle) insulin action, which is not due to changes in body composition. These results suggest that circulating IGF-II may exert a regulatory role on insulin sensitivity and body composition in humans.
Adult↗
International comparison of hip fracture rates in 1988-89.
A comparison of hip fracture rates among nine countries (Canada, Chile, Finland, Hong Kong, Scotland, Sweden, Switzerland, the United States and Venezuela) was made using national hospital discharge data for the same time interval. The rates increased by age and were higher for females than males in all nine countries. When based on overall discharge rates, the incidence of hip fracture appeared high in three European countries (Finland, Scotland and Sweden) relative to the other countries. However, when transfer cases were removed and adjustments made for differences in case definition, the risk of hip fracture for both men and women was much similar among the four European and two North American countries, but higher than in Hong Kong. Rates of fracture were lowest in Venezuela and Chile, varying from three to 11 times less than for residents of the other seven countries. Although there are limitations in using hospital discharge data as a measure of incidence, the wide variation in the risk of hip fracture across the nine countries appears real but differences between North American and north European countries may not be as great as previously reported. Such cross-national comparisons may help clarify different etiologic hypotheses.
Age Factors↗
Metabolically active component of fat-free body mass: influences of age, adiposity, and gender.
Fat-free body mass (FFM) is often considered the metabolically active compartment and is widely used to adjust between-subject differences in resting energy expenditure for body composition. The use of FFM as the metabolically active portion of body weight makes the assumption that the body cell mass (BCM) component which is more difficult to measure, maintains a relatively constant relationship to FFM within and between subjects. The aim of this study was to test the hypothesis that BCM and FFM are associated independently of age, adiposity (as represented by body density), and gender in healthy white women and men. BCM and FFM were estimated by whole-body 40K-counting and dual-energy x-ray absorptiometry (DXA), respectively. Multiple regression analysis was used to model the relationships between BCM as the dependent variable and FFM, age, body density, and gender as potential independent variables. FFM alone explained 51% and 63% of between-individual BCM differences in women (n = 269) and men (n = 204) (both P = .0001), respectively. Age contributed significantly (P = .0001) to BCM prediction after adjusting first for FFM in both women and men. Body density also added significantly (P = .004 and P = .0001) to FFM and age prediction of BCM in women and men, respectively. Lastly, gender contributed significantly to the composite model, with 91% of between-individual differences in BCM explained by FFM, age, body density, and gender. Hence, BCM does not maintain a fixed relationship to FFM, as often assumed, but varies significantly and independently of FFM with age, adiposity, and gender. These findings have implications for the study of metabolic indices such as resting energy expenditure.
Absorptiometry, Photon↗
Weight, height and body mass index distributions in geographically and ethnically diverse samples of older persons. Ad Hoc Committee on the Statistics of Anthropometry and Aging.
We compared anthropometric data (height, weight and body mass index) from 19 geographically and ethnically varied samples of community-dwelling elderly people. Participants were stratified into three age groups, 60-69, 70-79 and 80 years or older. We present age-group-specific means and standard deviations for height, weight and body mass index (BMI, weight/height2) and the prevalence of underweight (BMI < 20) and overweight (BMI > or = 30). Across studies there are large differences in the prevalence of overweight and underweight, but in all studies mean height and BMI decreased with age. In general, mean BMI among 70-79-year-old women is greater than that for men of a similar age, and the Mediterranean samples are heavier for height than samples from Western Europe, Asia, Africa and the United States. The comparisons suggest that the sensitivity and specificity of a fixed cut-off for underweight and overweight are likely to differ by sex, age, and geographic location in samples of older persons.
Aged↗