E Jeffrey Metter

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (210)949.18 Total impact

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    ABSTRACT: Objective: To determine whether there are differences in prostate specific antigen (PSA) at diagnosis or changes in PSA between US and European populations of men with and without prostate cancer. Subjects and methods: Repeated measures of PSA from six clinically and geographically diverse patient cohorts: two cohorts of men with PSA-detected prostate cancer, two cohorts with clinically-detected prostate cancer and two cohorts of men without prostate cancer. Using multilevel models, average PSA at diagnosis and PSA change over time were compared between populations. Results: Annual percentage PSA change of 4-5% was similar between men without cancer and men with PSA-detected cancer. PSA at diagnosis was 1.7ng/ml lower in a US cohort of PSA-detected men (95% CI 1.3-2.0ng/ml), compared to a PSA-detected UK cohort, but there was no evidence for a different rate of PSA change between these populations. Conclusion: PSA changes over time are similar in UK and US men diagnosed through PSA testing and even in men without prostate cancer. Further development of PSA models to monitor men on active surveillance should be undertaken in order to take advantage of these similarities. We found no evidence that guidelines for using PSA to monitor men cannot be passed between US and European studies. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2016 · BJU International
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    ABSTRACT: Background: Forced expiratory volume in 1 second (FEV1) over time is commonly expressed in liters and percent predicted (%Pred), or alternatively in L/m(3) and Z-scores-which approach is more clinically meaningful has not been evaluated. Because it uniquely accounts for the effect of aging on FEV1 and spirometric performance, we hypothesized that the Z-score approach is more clinically meaningful, based on associations between cardiopulmonary predictors and FEV1 over time. Methods: Using linear mixed-effects models and data from the Baltimore Longitudinal Study on Aging, including 501 white participants aged 40-95 who had completed at least three longitudinal spirometric assessments, we evaluated the associations between cardiopulmonary predictors (obesity, smoking status, hypertension, chronic bronchitis, diabetes mellitus, and myocardial infarction) and FEV1 over time, in liters, %Pred, L/m(3), and Z-scores. Results: Mean baseline values for FEV1 were 3.240L, 96.4%Pred, 0.621L/m(3), and -0.239 as a Z-score (40.6th percentile). The annual decline in FEV1 was 0.040L, 0.234 %Pred, 0.007L/m(3), and 0.008 Z-score units. Baseline age was associated with FEV1 over time in liters and L/m(3) (p < .001), and included a time interaction for %Pred (p < .001), but was not associated with Z-scores (p = .933). The associations of cardiopulmonary predictors with FEV1 over time were all significant when using Z-scores (p < .05), but varied for other methods of expressing FEV1. Conclusion: A Z-score approach is more clinically meaningful when evaluating FEV1 over time, as it accounted for the effect of aging and was more frequently associated with multiple cardiopulmonary predictors.
    No preview · Article · Nov 2015 · The Journals of Gerontology Series A Biological Sciences and Medical Sciences
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    ABSTRACT: Polymorphisms in the vitamin D receptor (VDR) gene are some of the most studied in relation to skeletal muscle traits and significant associations have been observed by multiple groups. One such paper by our group provided the first evidence of a genetic association with sarcopenia in men, but that finding has yet to be replicated in an independent cohort. In the present study, we examined multiple VDR polymorphisms in relation to skeletal muscle traits and sarcopenia in 864 men and women across the adult age span. In addition to VDR genotypes and haplotypes, measurements of skeletal muscle strength and fat-free mass (FFM) were determined in all subjects and a measure of sarcopenia was calculated. We observed significant associations between Fok1 and Bsm1 genotypes and skeletal muscle strength in men and women, though these associations were modest and no significant associations were observed for these polymorphisms and muscle mass traits nor for Bsm1-Taq1 haplotype with muscle strength. Fok1 FF genotype was associated with an increased the risk of sarcopenia in older women compared to f-allele carriers (1.3-fold higher risk). These results support previous findings that VDR genetic variation appears to impact skeletal muscle strength and risk for sarcopenia but the influence is modest.
    No preview · Article · Sep 2015 · Aging - Clinical and Experimental Research
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    ABSTRACT: The TCR repertoire serves as a reservoir of TCRs for recognizing all potential pathogens. Two major types of T cells, CD4(+) and CD8(+), that use the same genetic elements and process to generate a functional TCR differ in their recognition of peptide bound to MHC class II and I, respectively. However, it is currently unclear to what extent the TCR repertoire of CD4(+) and CD8(+) T cells is different. Here, we report a comparative analysis of the TCRβ repertoires of CD4(+) and CD8(+) T cells by use of a 5' rapid amplification of cDNA ends-PCR-sequencing method. We found that TCRβ richness of CD4(+) T cells ranges from 1.82 to 9.8 × 10(4) and is approximately 5 times greater, on average, than that of CD8(+) T cells in each study subject. Furthermore, there was little overlap in TCRβ sequences between CD4(+) (0.3%) and CD8(+) (1.3%) T cells. Further analysis showed that CD4(+) and CD8(+) T cells exhibited distinct preferences for certain amino acids in the CDR3, and this was confirmed further by a support vector machine classifier, suggesting that there are distinct and discernible differences between TCRβ CDR3 in CD4(+) and CD8(+) T cells. Finally, we identified 5-12% of the unique TCRβs that share an identical CDR3 with different variable genes. Together, our findings reveal the distinct features of the TCRβ repertoire between CD4(+) and CD8(+) T cells and could potentially be used to evaluate the competency of T cell immunity.
    Full-text · Article · Sep 2015 · Journal of leukocyte biology
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    ABSTRACT: Background: Telomeres provide a key mechanism for protecting the integrity of chromosomes and their attrition after cell division and during aging are evident in lymphocytes. However, the significance of telomere shortening in age-associated decline of immune function is unknown. Methods: We selected 22 HLA-A2-positive healthy older adults who have relatively short or long telomere lengths to compare their antibody response against the influenza vaccine, and their CD8(+) T-cell response against an influenza antigen. Results: B cells from individuals with a robust antibody response to the influenza vaccine had significantly longer telomeres than those with a poor antibody response. Monocyte-derived antigen-presenting cells of both short and long telomere groups induced similar expansions of influenza M1-specific CD8(+) T cells. Vaccination did not increase M1-specific CD8(+) T cells in blood, but M1-specific CD8(+) T cells from the long telomere group exhibited significantly greater expansion in vitro than those from the short telomere group. Finally, M1-specific CD8(+) T cells that underwent more expansions had significantly longer telomeres than cells with fewer divisions. Conclusions: Telomere length is positively associated with a robust lymphocyte response, and telomere attrition may contribute to the age-associated decline of adaptive immunity.
    Full-text · Article · Mar 2015 · The Journal of Infectious Diseases
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    ABSTRACT: Many studies of aging examine biomarkers one at a time, but complex systems theory and network theory suggest that interpretations of individual markers may be context-dependent. Here, we attempted to detect underlying processes governing the levels of many biomarkers simultaneously by applying principal components analysis to 43 common clinical biomarkers measured longitudinally in 3694 humans from three longitudinal cohort studies on two continents (Women's Health and Aging I & II, InCHIANTI, and the Baltimore Longitudinal Study on Aging). The first axis was associated with anemia, inflammation, and low levels of calcium and albumin. The axis structure was precisely reproduced in all three populations and in all demographic sub-populations (by sex, race, etc.); we call the process represented by the axis "integrated albunemia." Integrated albunemia increases and accelerates with age in all populations, and predicts mortality and frailty - but not chronic disease - even after controlling for age. This suggests a role in the aging process, though causality is not yet clear. Integrated albunemia behaves more stably across populations than its component biomarkers, and thus appears to represent a higher-order physiological process emerging from the structure of underlying regulatory networks. If this is correct, detection of this process has substantial implications for physiological organization more generally.
    Full-text · Article · Mar 2015 · PLoS ONE
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    ABSTRACT: Telomeres are essential in maintaining chromosome integrity and in controlling cellular replication. Attrition of telomere length in peripheral blood mononuclear cells (PBMCs) with age is well documented from cross-sectional studies. But the actual in vivo changes in telomere lengths and its relationship with the contributing factors within the individuals with age have not been fully addressed. In the present paper, we report a longitudinal analysis of telomere length in the PBMCs, lymphocytes and monocytes of 216 human subjects aged from 20-90 years assessed at 0-, 5- and 12-year follow-up. For the 5- and 12-year follow-up, telomere length in the PBMCs decreased in 34% and 46%, exhibited no detectable change in 56% and 47% and increased in 10% and 7% of the subjects respectively. The rate of telomere change was distinct for T-cells, B-cells and monocytes for any given subject. Telomerase activity declined with age in the resting T-cells and B-cells and the activated T-cells. Finally, a significant portion of telomere attrition in T-cells with age was explained by a decline in the telomerase activity, decreased naive cells and the change in physiological conditions such as elevated blood glucose and interleukin (IL)-6 levels. These findings show that changes in the telomere length of the PBMCs with age in vivo occur at different rates in different individuals and cell types and reveal that changes in the telomere length in the T-cells with age is influenced by the telomerase activity, naive T-cell percentage and changes in health conditions.
    No preview · Article · Mar 2015 · Clinical Science
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    ABSTRACT: Objective: Persons with diabetes have accelerated muscle loss compared with their counterparts. The relationship of hyperglycemia per se to declines in muscle function has not been explored yet has implications for developing appropriate intervention strategies to prevent muscle loss. Research design and methods: We examined 984 participants aged 25-96 years in the Baltimore Longitudinal Study of Aging (2003-2011) with HbA1c, knee extensor strength (isokinetic dynamometer), and lean body mass (DEXA) measured at baseline. Participants had repeated measurements up to 7.5 years later. Muscle quality was defined as knee extensor strength/leg lean mass. Participants were categorized by HbA1c quartile (<5.5, 5.5-5.79, 5.8-6.09, and ≥6.1% or <37, 37-40, 40-43, and ≥43 mmol/mol). Mixed-effects regression models were used to examine the regression of muscle outcomes on HbA1c. Results: Muscle strength and quality were significantly lower across HbA1c quartiles (both P < 0.001), without differences in muscle mass at baseline. Comparing highest versus lowest HbA1c quartiles and adjusting for age, race, sex, weight, and height, strength was significantly lower (-4.70 ± 2.30 N · m; P value trend = 0.02) and results were unchanged after adjustment for physical activity (P value trend = 0.045) but of borderline significance after additional adjustment for peripheral neuropathy (P value trend = 0.05). Adjusting for demographics, muscle quality was significantly lower (-0.32 ± 0.15 N · m/kg; P value trend = 0.02) in the highest versus lowest HbA1c quartiles, but differences were attenuated after adjusting for weight and height (-0.25 ± 0.15 N · m/kg; P value trend = 0.07). Muscle mass measures were similar across HbA1c quartiles. Conclusions: Hyperglycemia is associated with persistently lower muscle strength with aging, but this effect may be mediated, at least in part, by peripheral neuropathy. Future studies should explore if better glycemic control can preserve muscle function in diabetes.
    No preview · Article · Nov 2014 · Diabetes Care
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    ABSTRACT: To examine differences in a proxy measure of muscle quality across the adult life span and explore potential mechanisms of muscle quality change through identification of cross-sectional correlates of muscle quality. Cross-sectional study. Baltimore Longitudinal Study of Aging. Seven hundred eighty-six individuals with a mean age of 66.3 (range 26-96) (N = 786). A sensitivity analysis was conducted in a subset of participants matched according to sex, muscle mass, and body size. Muscle quality was operationalized as the ratio of knee-extension strength (isokinetic dynamometry) to thigh muscle cross-sectional area (computed tomography). Differences in muscle strength, muscle area, and muscle quality ratio with age were evaluated, and the association between the muscle quality ratio and measures reflecting domains of cognitive function, motor control, peripheral nerve function, adiposity, glucose homeostasis, and inflammation were assessed through multivariate regression analyses. A linear relationship between age and muscle quality ratio was observed, suggesting a gradual decline in muscle quality over the adult life course. Associations were observed between muscle quality ratio and measures of adiposity, as well as peroneal nerve motor conduction velocity, finger tapping speed, and memory performance (P < .01). The association between muscle quality ratio and nerve conduction velocity was maintained after adjustment for anthropometric measurements (P < .05). Muscle quality declines progressively with age over the adult life span and is affected by obesity and neurological factors. Studies are needed to clarify the mechanisms of these associations and their implications for functional outcomes.
    No preview · Article · Jan 2014 · Journal of the American Geriatrics Society
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    ABSTRACT: Repeated failure in the Army Physical Fitness Test (APFT) is associated with lower fitness level, premature discharge, and significant career disruption, at high economic and health costs to the individual soldier and the U.S. Army. We used cost-effectiveness analysis to estimate the health and economic implications of two exercise interventions for Army National Guard (ARNG) soldiers who had failed the APFT, a traditional remediation program and a new pedometer-based program called Fitness for Life, involving individual counseling and follow-up telephone calls. Effectiveness of the interventions was analyzed in terms of APFT pass rates and calculated 10-year coronary heart disease risk. Costs were calculated based on tracking of resources used in the programs. APFT pass rates were 54.3% and 47.9%, respectively, for traditional and Fitness for Life programs, p = not significant. Neither program affected 10-year coronary heart disease risk. For assumed APFT pass rates up to 40% without any formal remediation, both the traditional remediation program and the ARNG Fitness for Life intervention had cost savings without significant group differences. Depending on the ARNG unit and personnel preference, although the Fitness for Life Program was more expensive and thus less cost-effective, either program could be cost-effective and of benefit to the military.
    Full-text · Article · Dec 2013
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    ABSTRACT: IMPORTANCE Peripheral glucose homeostasis has been implicated in the pathogenesis of Alzheimer disease (AD). The relationship among diabetes mellitus, insulin, and AD is an important area of investigation. However, whether cognitive impairment seen in those with diabetes is mediated by excess pathological features of AD or other related abnormalities, such as vascular disease, remains unclear. OBJECTIVE To investigate the association between serial measures of glucose intolerance and insulin resistance and in vivo brain β-amyloid burden, measured with carbon 11-labeled Pittsburgh Compound B (11C-PiB), and AD pathology at autopsy. DESIGN Scores calculated from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and Braak criteria were correlated with measures of hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance in 197 participants who underwent autopsy after death and who had undergone 2 or more oral glucose tolerance tests (OGTT) using grouped analyses and a continuous mixed-models analysis. The same measures of glucose intolerance and insulin resistance were also correlated with brain 11C-PiB retention in an additional 53 living subjects from the Baltimore Longitudinal Study of Aging neuroimaging study. SETTING Prospective, serially assessed cohort of community-dwelling subjects. PARTICIPANTS Cohort 1 consisted of 197 participants enrolled in the Baltimore Longitudinal Study of Aging who had 2 or more OGTTs during life and a complete brain autopsy after death. Cohort 2 consisted of 53 living subjects who had 2 or more OGTTs and underwent brain 11C-PiB positron emission tomography. EXPOSURES Autopsy and 11C-PiB positron emission tomography. MAIN OUTCOMES AND MEASURES The correlation of brain markers of AD, including CERAD score, Braak score, and 11C-PiB retention, with serum markers of glucose homeostasis using grouped and continuous mixed-models analyses. RESULTS We found no significant correlations between measures of brain AD pathology or 11C-PiB β-amyloid load and glucose intolerance or insulin resistance in subjects who had a mean (SD) of 6.4 (3.2) OGTTs during 22.1 (8.0) years of follow-up. Thirty subjects with frank diabetes mellitus who received medications also had AD pathology scores that were similar to those of the cohort as a whole. CONCLUSIONS AND RELEVANCE In this prospective cohort with multiple assessments of glucose intolerance and insulin resistance, measures of glucose and insulin homeostasis are not associated with AD pathology and likely play little role in AD pathogenesis. Long-term therapeutic trials are important to elucidate this issue.
    No preview · Article · Jul 2013
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    ABSTRACT: Objective To identify a standard physical performance test, which can predict 3-year incident mobility disability independent of demographics. Design Longitudinal cohort study. Setting Population-based middle-aged and older adult cohort assessment performed at a local geriatric clinical center. Participants Community-living middle-aged and older persons (age, 50–85y) without baseline mobility disability (N=622). Interventions Not applicable. Main Outcome Measures Mobility disability was ascertained at baseline and at 3-year follow-up using an established self-report method: self-reported inability to walk a quarter mile without resting or inability to walk up a flight of stairs unsupported. Physical performance tests included self-selected usual gait speed, time required to complete 5 times sit-to-stand (5TSTS), and 400-m brisk walking. Demographic variables age, sex, height, and weight were recorded. Results Overall, 13.5% participants reported 3-year incident mobility disability. Usual gait speed <1.2m/s, requiring >13.6 seconds to complete 5TSTS, and completing 400m at <1.19m/s walking speed were highly predictive of future mobility disability independent of demographics. Conclusions Inability to complete 5TSTS in <13.7 seconds can be a clinically convenient guideline for monitoring and for further assessment of middle-aged and older persons, in order to prevent or delay future mobility disability.
    Full-text · Article · May 2013 · Archives of Physical Medicine and Rehabilitation
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    ABSTRACT: Objective: To investigate whether the performance on 5 times sit-to-stand test (5tSTS) can predict subsequent falls, fall-related fracture, and activities of daily living (ADL) and instrumental activities of daily living (IADL) disability in older persons. Methods: A total of 948 older adults (age ≥ 60) participated in this study. Ability and the time to finish 5tSTS were recorded at baseline. Number of falls, fall-related fractures, and the ability to complete ADL and IADL without assistance were recorded retrospectively at baseline and at the 3-year follow-up. Results: Inability to complete 5tSTS was a marginal predictor of falls (OR = 4.22) and a significant predictor of ADL- (OR = 24.70) and IADL-related disability (OR = 17.10) at 3-year follow-up. The need of longer time to complete 5tSTS was predictive of developing IADL-related disability at 3-year follow-up (OR = 4.22 [> 16.6 s]; OR = 2.49 [13.7 - 16.6 s]). Discussion: 5tSTS is an easily administered tool which can be used to predict subsequent ADL- and IADL-related disability.
    No preview · Article · Feb 2013 · Journal of Aging and Health
  • Nandini Deshpande · E Jeffrey Metter · Jack Guralnik · Luigi Ferrucci
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    ABSTRACT: This study examined whether inability to perform adaptive locomotor tests predicts self-reported incident mobility disability. InCHIANTI study participants (N = 611; age, 50-85 yrs) who could walk 7 m at self-selected speed and who had no self-reported mobility disability at baseline were included. The ability to complete four adaptive locomotor tests was assessed: fast walking, walking on a narrow path, crossing obstacles while walking, and talking while walking. Mobility disability was recorded again at 3-yr follow-up. Failure in the fast-walking and narrow-path walking tests predicted approximately 2.5 times likelihood of reporting incident mobility disability (P = 0.009 and P = 0.011, respectively). Failure in the obstacle-crossing test predicted approximately two times likelihood of reporting incident mobility disability; however, this result did not reach statistical significance (P = 0.077). Failure in talking while walking did not predict incident mobility disability. Those who failed both the fast-walking and narrow-path walking tests were almost nine times as likely to report incident mobility disability.
    No preview · Article · Jan 2013 · American journal of physical medicine & rehabilitation / Association of Academic Physiatrists
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    ABSTRACT: Associations among personality as measured by the Five Factor Model, physical activity, and muscle strength were assessed using data from the Baltimore Longitudinal Study of Aging (N = 1220, age: mean = 58, SD = 16). General linear modeling with adjustment for age, sex, race, and body mass index, and bootstrapping for mediation were used. We found neuroticism and most of its facets to negatively correlate with strength. The extraversion domain and its facets of warmth, activity, and positive-emotions were positively correlated with strength, independent of covariates. Mediation analysis results suggest that these associations are partly explained by physical activity level. Findings extend the evidence of an association between personality and physical function to its strength component and indicate health behavior as an important pathway.
    Full-text · Article · Jun 2012 · Journal of Research in Personality
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    Christopher H Morrell · Larry J Brant · Shan Sheng · E Jeffrey Metter
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    ABSTRACT: Using several variables known to be related to prostate cancer, a multivariate classification method is developed to predict the onset of clinical prostate cancer. A multivariate mixed-effects model is used to describe longitudinal changes in prostate specific antigen (PSA), a free testosterone index (FTI), and body mass index (BMI) before any clinical evidence of prostate cancer. The patterns of change in these three variables are allowed to vary depending on whether the subject develops prostate cancer or not and the severity of the prostate cancer at diagnosis. An application of Bayes' theorem provides posterior probabilities that we use to predict whether an individual will develop prostate cancer and, if so, whether it is a high-risk or a low-risk cancer. The classification rule is applied sequentially one multivariate observation at a time until the subject is classified as a cancer case or until the last observation has been used. We perform the analyses using each of the three variables individually, combined together in pairs, and all three variables together in one analysis. We compare the classification results among the various analyses and a simulation study demonstrates how the sensitivity of prediction changes with respect to the number and type of variables used in the prediction process.
    Full-text · Article · Jun 2012 · Journal of Applied Statistics
  • Seung-uk Ko · Sari Stenholm · E Jeffrey Metter · Luigi Ferrucci
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    ABSTRACT: The aim of the present study was to examine differences in gait characteristics across the adult lifespan and to test the hypothesis that such differences are attributable at least in part to the decline in muscle strength. The data presented here are from 190 participants of the Baltimore Longitudinal Study of Aging (BLSA) aged from 32 to 93 years. Based on two age thresholds that best capture the effect of age on walking speed, participants were divided into three age groups: middle-age (32-57 years; N=27), old-age (58-78 years; N=125), and oldest-age (79-93 years; N=38). Participants were asked to walk at their preferred and maximum speeds while recorded with 3D gait analysis system. In addition, maximum isokinetic knee extensor strength was assessed. While walking at preferred speed, range of motion (ROM) and mechanical work expenditure (MWE) of the ankle were lower within middle-age (p<0.001, p=0.047, respectively), while hip ROM and MWE were lower (p=0.006) and higher (p<0.001), respectively within oldest-age with older age. Deterioration in ankle function during customary walking initiates already at middle-age. Differences in the maximum walking speed and ankle ROM between middle-age and old-age were explained by knee strength.
    No preview · Article · May 2012 · Archives of gerontology and geriatrics
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    ABSTRACT: To study the relationships between muscle mass, regional adiposity, and adipokines and glucose disposal in an older population. Cross-sectional analysis. Community-dwelling volunteers from the Baltimore Longitudinal Study of Aging. Two hundred eighty men and 259 women with a mean age of 71.1 ± 0.4 (range 55-96) and complete data on fasting plasma adiponectin and leptin, oral glucose tolerance test (OGTT) (plasma glucose available at 0, 20, 40, 60, 80, 100, and 120 minutes), thigh computed tomography (CT), physical activity levels, and anthropometric measures. Participants were classified into eight groups according to the presence of global adiposity (body mass index > 27 kg/m(2)), central adiposity (waist circumference > 88 cm for women and > 102 cm for men), and low muscle mass (CT thigh, lowest sex-specific tertile (93.8 cm(2) in women and 110.7 cm(2) in men) of adjusted thigh muscle area). Linear regression models were used to estimate the contribution of these eight groups to early glucose area under the curve (AUC) (t = 0-40 minutes), late glucose AUC (t = 60-120 minutes), and total glucose AUC (t = 0-120 minutes) from the OGTT. Regardless of muscle mass, individuals with a combination of central and global adiposity were more likely to have delayed glucose disposal rates (P < .05). A strong negative association was also found between circulating adiponectin levels and glucose disposal rates (early AUC, β = -0.14; late AUC, β = -0.20; and total AUC, β = -0.20; P < .05 for all three AUCs) after adjusting for regional adiposity, muscle mass, circulating leptin levels, physical activity, age, and sex. Older individuals with global and central adiposity may be at risk of glucose intolerance unrelated to low muscle mass.
    Preview · Article · Mar 2012 · Journal of the American Geriatrics Society
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    ABSTRACT: •  To determine whether the prostate-specific antigen velocity (PSAV) risk count (i.e. the number of times PSAV exceeds a specific threshold) could increase the specificity of screening for prostate cancer and potentially life-threatening tumours. •  From 1989 to 2001, we calculated two serial PSAV measurements in 18 214 prostate cancer screening-study participants, of whom 1125 (6.2%) were diagnosed with prostate cancer. •  The PSAV risk count was determined as the number of PSAV measurements of >0.4 ng/mL/year (0, 1, or 2). •  We used receiver operating characteristic (ROC) and reclassification analyses to examine the ability of PSAV risk count to predict screen-detected and high-grade prostate cancer. •  The PSAV was >0.4 ng/mL/year twice (risk count 2) in 40% of prostate cancer cases compared with only 4% of those with no cancer (P < 0.001). •  After adjusting for age and PSA level, a PSAV risk count of 2 was associated with an 8.2-fold increased risk of prostate cancer (95% confidence interval 7.0-9.6, P < 0.001) and 5.4-fold increased risk of Gleason score 8-10 prostate cancer on biopsy. •  Compared with a model with age and PSA level, the addition of the PSAV risk count significantly improved discrimination (area under the ROC curve 0.625 vs 0.725, P= 0.031) and reclassified individuals for the risk of high-grade prostate cancer (net reclassification, P < 0.001). •  Sustained rises in PSA indicate a significantly greater risk of prostate cancer, particularly high-grade disease. •  Compared with men with a risk count of ≤1, those with two PSAV measurements of >0.4 ng/mL/year (risk count 2) had an 8-fold increased risk of prostate cancer and 5.4-fold increased risk of Gleason 8-10 disease on biopsy, adjusting for age and PSA level. •  Compared to PSA alone, PSAV risk count may be useful in reducing unnecessary biopsies and the diagnosis of low-risk prostate cancer.
    Full-text · Article · Feb 2012 · BJU International
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    ABSTRACT: Study Type – Prognostic (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Previous studies have attempted to characterize the normal biological variability in PSA among men without prostate cancer. These reports suggest that PSA variability is unrelated to age, but there are conflicting data on its association with the baseline PSA level. There are limited published data regarding the effects of prostate volume on PSA variability. A prior study assessing whether prostate volume changes would confound the use of PSA velocity in clinical practice reported that prostate volume changes were not significantly related to PSA changes. This study did not directly address the effect of baseline prostate volume on serial PSA variability. The objective of the current study was to further examine the relationship between prostate volume and PSA variability. Our hypothesis was that larger baseline prostate volume would be associated with increased PSA variability in men without known prostate cancer and in those with suspected small-volume disease. The results of the study suggest that baseline PSA, not prostate volume, is the primary driver of PSA variability in these populations.
    No preview · Article · Nov 2011 · BJU International

Publication Stats

10k Citations
949.18 Total Impact Points


  • 1997-2015
    • Johns Hopkins University
      • • School of Nursing
      • • Department of Pathology
      Baltimore, Maryland, United States
  • 1989-2015
    • National Institute on Aging
      • • Clinical Research Branch (CRB)
      • • Intramural Research Program (IRP)
      • • Laboratory of Clinical Investigation (LCI)
      Baltimore, Maryland, United States
  • 2012
    • National Institute of Aerospace
      Hampton, Virginia, United States
  • 2011
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 2010
    • Queen's University
      • School of Rehabilitation Therapy
      Kingston, Ontario, Canada
    • WWF United Kingdom
      Londinium, England, United Kingdom
    • University of Maryland, Baltimore County
      • Department of Psychology
      Baltimore, Maryland, United States
  • 1995-2010
    • Johns Hopkins Medicine
      • Department of Urology
      Baltimore, Maryland, United States
  • 2007-2009
    • National Institutes of Health
      • Clinical Research Branch (CRB)
      Maryland, United States
    • Università degli studi di Parma
      • Department of Clinical and Experimental Medicine
      Parma, Emilia-Romagna, Italy
    • Università degli Studi di Perugia
      • Department of Clinical and Experimental Medicine
      Perugia, Umbria, Italy
  • 2008
    • Grays Harbor Community Hospital
      Aberdeen, Washington, United States
    • Loyola University Maryland
      Baltimore, Maryland, United States
  • 2006
    • National Institute of Clinical Research
      Georgia, United States
  • 2000-2004
    • University of Maryland Eastern Shore
      • Department of Physical Therapy
      Maryland, United States
  • 2002
    • Dokkyo Medical University
      • Division of Rehabilitation Medicine
      Totigi, Tochigi, Japan
  • 2001
    • University of California, San Francisco
      San Francisco, California, United States
    • University of Pittsburgh
      • Department of Human Genetics
      Pittsburgh, Pennsylvania, United States
  • 1999
    • Osaka University
      Suika, Ōsaka, Japan
  • 1988
    • California State University, Northridge
      Northridge, Ohio, United States
  • 1980-1988
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      • Department of Medicine
      Torrance, California, United States
  • 1980-1987
    • University of California, Los Angeles
      • Department of Medicine
      Los Angeles, California, United States
  • 1983
    • University of California, San Diego
      San Diego, California, United States