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Ronenn Roubenoff

Publications and source records attributed to Ronenn Roubenoff.

At least 37 records · Page 2Linked to original sources
PubMed2004

The healthcare costs of sarcopenia in the United States.

OBJECTIVES: To estimate the healthcare costs of sarcopenia in the United States and to examine the effect that a reduced sarcopenia prevalence would have on healthcare expenditures. DESIGN: Cross-sectional surveys. SETTING: Nationally representative surveys using data from the U.S. Census, Third National Health and Nutrition Examination Survey, and National Medical Care and Utilization Expenditure Survey. PARTICIPANTS: Representative samples of U.S. adults aged 60 and older. MEASUREMENTS: The healthcare costs of sarcopenia were estimated based on the effect of sarcopenia on increasing physical disability risk in older persons. In the first step, the healthcare cost of disability in older Americans was estimated from national surveys. In the second step, the proportion of the disability cost due to sarcopenia (population-attributable risk) was calculated to determine the healthcare costs of sarcopenia. These calculations relied upon previously published relative risk values for disability in sarcopenic individuals and sarcopenia prevalence rates in the older population. RESULTS: The estimated direct healthcare cost attributable to sarcopenia in the United States in 2000 was $18.5 billion ($10.8 billion in men, $7.7 billion in women), which represented about 1.5% of total healthcare expenditures for that year. A sensitivity analysis indicated that the costs could be as low as $11.8 billion and as high as $26.2 billion. The excess healthcare expenditures were $860 for every sarcopenic man and $933 for every sarcopenic woman. A 10% reduction in sarcopenia prevalence would result in savings of $1.1 billion (dollars adjusted to 2000 rate) per year in U.S. healthcare costs. CONCLUSION: Sarcopenia imposes a significant but modifiable economic burden on government-reimbursed healthcare services in the United States. Because the number of older Americans is increasing, the economic costs of sarcopenia will escalate unless effective public health campaigns aimed at reducing the occurrence of sarcopenia are implemented.

Activities of Daily Living↗
PubMed2004

Tumor necrosis factor-alpha production is associated with less body cell mass in women with rheumatoid arthritis.

OBJECTIVE: To examine the relationship between inflammatory cytokine production and body cell mass (BCM) in women with stable, medically well-controlled rheumatoid arthritis (RA). METHODS: Case-control study of 20 women with RA and 20 healthy women matched for age, race, and body mass index (kg/m2). Tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-6 production were measured by specific, non-cross-reacting ELISA of peripheral blood mononuclear cells (PBMC) cultured with and without 100 ng/ml of endotoxin. Total BCM was assessed by the reference method of whole-body counting of naturally occurring radioactive potassium-40. RESULTS: Patients with RA were cachectic, with 14% less BCM (p < 0.001) and higher TNF-alpha production (p < 0.05) than controls. TNF-alpha production was inversely associated with BCM both without (r = -0.51, p = 0.03) and with (r = -0.57, p = 0.01) endotoxin stimulation in patients but not in controls. In multivariate linear regression models, these inverse associations remained significant after adjustment for age and physical activity. No association was found for IL-1beta or IL-6 production in these models. CONCLUSION: Women with stable, medically well-controlled RA have lower than normal BCM that is inversely associated with elevated TNF-alpha production.

Adult↗
PubMed2003

Serum insulin-like growth factor I and risk for heart failure in elderly individuals without a previous myocardial infarction: the Framingham Heart Study.

BACKGROUND: Several experimental investigations have emphasized the favorable effects of insulin-like growth factor I (IGF-I) on left ventricular remodeling, partly through its antiapoptotic effects. Cross-sectional clinical studies have reported that low serum IGF-I levels in patients with heart failure correlate with cachexia and severity of ventricular dysfunction. It is unclear whether low serum IGF-I is a risk factor for heart failure. OBJECTIVE: To prospectively study the association between serum IGF-I level and the incidence of congestive heart failure. DESIGN: Community-based, prospective cohort study. SETTING: Framingham, Massachusetts. PARTICIPANTS: 717 elderly individuals (mean age, 78.4 years; 67% women) who did not have myocardial infarction and congestive heart failure at baseline. MEASUREMENT: Incidence of a first episode of congestive heart failure on follow-up. RESULTS: During follow-up (mean, 5.2 years), 56 participants (35 women) developed congestive heart failure. In multivariable Cox regression models adjusting for established risk factors at baseline, there was a 27% decrease in risk for heart failure for every 1 standard deviation increment in log IGF-I. Individuals with serum IGF-I level at or above the median value (140 microg/L) had half the risk for heart failure (hazard ratio, 0.49 [95% CI, 0.26 to 0.92]) of those with serum IGF-I levels below the median. These comparisons were maintained in analyses adjusting for the occurrence of a myocardial infarction on follow-up. CONCLUSIONS: In our prospective, community-based investigation, serum IGF-I level was inversely related to the risk for congestive heart failure in elderly people without a previous myocardial infarction. Additional investigations are warranted to confirm these findings.

Aged↗
PubMed2003

Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study.

BACKGROUND: Aging is associated with increased production of catabolic cytokines, reduced circulating levels of insulin-like growth factor 1 (IGF-1), and acceleration of sarcopenia (loss of muscle with age). We hypothesized that these factors are independently linked to mortality in community-dwelling older persons. METHODS: We examined the relation of all-cause mortality to peripheral blood mononuclear cell production of inflammatory cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin 1 beta, interleukin 6), serum interleukin 6 and IGF-1, and fat-free mass and clinical status in 525 ambulatory, free-living participants in the Framingham Heart Study. RESULTS: Of the 525 subjects (aged 72 to 92 years at baseline), 122 (23%) died during 4 years of follow-up. After adjusting for age, sex, comorbid conditions, smoking, and body mass index, mortality was associated with greater cellular production of TNF-alpha (hazard ratio [HR] = 1.27 per log(10) difference in ng/mL; 95% confidence interval [CI]: 1.00 to 1.61; P = 0.05) and higher serum interleukin 6 levels (HR = 1.30 per log(10) difference in pg/mL; 95% CI: 1.04 to 1.63]; P = 0.02), but not with higher serum IGF-1 levels (HR = 0.70 per log(10) difference in pg/mL; 95% CI: 0.49 to 0.99; P = 0.04). In a subset of 398 subjects (55 deaths) in whom change in fat-free mass index during the first 2 years was measured, less loss of fat-free mass and greater IGF-1 levels were associated with reduced mortality during the next 2 years. CONCLUSION: Greater levels or production of the catabolic cytokines TNF-alpha and interleukin 6 are associated with increased mortality in community-dwelling elderly adults, whereas IGF-1 levels had the opposite effect.

Aged↗
PubMed2003

Effect of vitamin E and eccentric exercise on selected biomarkers of oxidative stress in young and elderly men.

Muscle damage resulting from eccentric exercise provides a useful model of oxyradical-induced injury and can be used to examine age-related responses to oxidative stress. Sixteen young (26.4 +/- 3.3 years) and 16 older (71.1 +/- 4.0 years) healthy men were randomly assigned to 1000 IU/d vitamin E or placebo for 12 weeks and ran downhill for 45 min at 75% VO(2)max, once before and following supplementation. Blood samples were obtained before (baseline) and immediately postexercise (0 h), and at 6, 24, and 72 h postexercise to determine antioxidant status, muscle damage, lipid peroxidation, and DNA damage. Following exercise, young and older men experienced similar increases in serum creatine kinase (CK), F(2alpha)-isoprostanes (iPF(2alpha); p <.001) and malondialdehyde (MDA; p <.01), although iPF(2alpha) peaked at 72 h postexercise and MDA peaked at 0 h. Oxygen Radical Absorbance Capacity (ORAC) decreased at 72 h (p <.01) and correlated with the rise in iPF(2alpha), MDA, and CK in the young men (p <.05). Leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG) was unaffected by exercise. Vitamin E decreased peak CK in young men, while in older men it decreased resting levels of iPF(2alpha) and suppressed the 24 h postexercise increases in iPF(2alpha) (p <.05). Thus, vitamin E supplementation induced modest changes eccentric exercise-induced oxidative stress, although differentially between the young and older subjects, while age had no direct influence on these responses among this group of physically fit subjects.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction: the Framingham Heart Study.

BACKGROUND: Experimental studies support a key role for cytokines in left ventricular remodeling. In congestive heart failure (CHF) patients, elevated plasma cytokine levels are associated with worse functional status and adverse prognosis. It is unclear whether cytokine levels can predict the incidence of CHF in asymptomatic individuals. METHODS AND RESULTS: We investigated the relations of serum interleukin-6 (IL-6), C-reactive protein (CRP), and spontaneous production of tumor necrosis factor-alpha (TNFalpha) by peripheral blood mononuclear cell (PBMC) to CHF incidence among 732 elderly Framingham Study subjects (mean age 78 years, 67% women) free of prior myocardial infarction and CHF. On follow-up (mean 5.2 years), 56 subjects (35 women) developed CHF. After adjustment for established risk factors, including the occurrence of myocardial infarction on follow-up, there was a 60 (PBMC TNFalpha) to 68% (serum IL-6) increase in risk of CHF per tertile increment in cytokine concentration (P=0.04, and 0.03, respectively, for trend). A serum CRP level > or =5 mg/dL was associated with a 2.8-fold increased risk of CHF (P=0.02). Subjects with elevated levels of all 3 biomarkers (serum IL-6 and PBMC TNFalpha >median values, CRP> or =5 mg/dL) had a markedly increased risk of CHF (hazards ratio 4.07 [95% CI 1.34 to 12.37], P=0.01) compared with the other subjects. CONCLUSIONS: In our elderly, community-based sample, a single determination of serum inflammatory markers, particularly elevated IL-6, was associated with increased risk of CHF in people without prior myocardial infarction. Additional epidemiological investigations are warranted to confirm the contribution of inflammation to the pathogenesis of CHF in the general population.

Aged↗
PubMed2003

Strength training in older women: early and late changes in whole muscle and single cells.

In order to examine the relative contribution of neural- and muscle-based adaptation to strength training, we studied early (2 weeks) and later (12 weeks) effects of strength training on muscle size and strength and type I single-fiber size and contractility in 14 elderly women (aged 68-79 years) and seven young controls. Older subjects were randomized to training (n = 7) or control (n = 7) groups. Strength did not change, but whole muscle size increased significantly after 2 weeks. After 12 weeks, strength, whole muscle size, and specific force all increased. No changes occurred in the control group. In single fibers, no changes in size and contractility were noted after 2 weeks, but specific force was higher in the training group after 12 weeks. Early adaptations to strength training in elderly women cannot be attributed to changes at the cellular level and therefore occur primarily in the central nervous system. Later, cellular adaptations in specific force track closely whole muscle changes.

Adult↗
PubMed2003

Abnormal vitamin B(6) status is associated with severity of symptoms in patients with rheumatoid arthritis.

PURPOSE: Patients with rheumatoid arthritis have low plasma vitamin B(6) levels and elevated plasma homocysteine responses to a methionine load. We examined whether these abnormalities are associated with clinical and biochemical indicators of disease status. METHODS: We performed a cross-sectional study in 37 patients who met the American College of Rheumatology criteria for rheumatoid arthritis. Vitamin B(6) status was assessed by the plasma pyridoxal 5'-phosphate level and with the homocysteine response to a methionine load test. Clinical disease activity was assessed by joint counts, the Health Assessment Questionnaire disability score, and biochemical markers of the acute phase response. RESULTS: Plasma pyridoxal 5'-phosphate levels were inversely correlated with the erythrocyte sedimentation rate (r = -0.37, P = 0.02), C-reactive protein level (r = -0.52, P = 0.002), disability score (r = -0.37, P = 0.02), morning stiffness (r = -0.38, P = 0.02), and degree of pain (r = -0.33, P = 0.04). The increase in homocysteine levels after a methionine load correlated with the erythrocyte sedimentation rate (r = 0.39, P = 0.02), C-reactive protein level (r = 0.37, P = 0.03), disability score (r = 0.37, P = 0.04), degree of pain (r = 0.38, P = 0.02) and fatigue (r = 0.42, P = 0.01), number of painful joints (r = 0.43, P = 0.007), and number of swollen joints (r = 0.32, P = 0.05). CONCLUSION: Markers of vitamin B(6) status are associated with disease activity and severity, synovial burden, and pain in patients with rheumatoid arthritis, raising the possibility that impaired vitamin B(6) status in these patients is a result of inflammation.

Adult↗
PubMed2003

Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men.

AIMS: The influence of ageing on the pharmacokinetics of zolpidem, an extensively prescribed hypnotic medication, was evaluated in healthy human volunteers. METHODS: A series of 16 elderly (age: 61-85 years) and 24 young (age: 22-42 years) volunteers received single 5 mg oral doses of zolpidem tartrate. Serum zolpidem concentrations were determined by HPLC with fluorescence detection in samples drawn during 8 h after dosage. The effect of testosterone on zolpidem biotransformation was evaluated in vitro using human liver microsomes. Possible induction of CYP3A protein expression and function was studied in cultured human hepatocytes. RESULTS: Among men, apparent oral clearance of zolpidem was decreased in elderly compared to young subjects (3.8 vs 11.0 ml min-1 kg-1, P < 0.01), Cmax was increased (93 vs 40 ng ml-1, P < 0.01), and half-life increased (2.7 vs 1.5 h, P < 0.03). Among women, zolpidem oral clearance was decreased in the elderly (3.0 vs 5.8 ml min-1 kg-1, P < 0.02), Cmax increased (108 vs 60 ng ml-1, P < 0.001), with no difference in t1/2 (2.3 vs 2.4 h). Among male subjects, free serum testosterone concentrations were lower in the elderly (10.5 vs 19.0 pg ml-1, P < 0.01), and were significantly correlated with zolpidem clearance (r2 = 0.46, P < 0.001). Multiple regression analysis indicated a greater relative contribution of serum testosterone than age to the oral clearance of zolpidem among men. In human liver microsomes, co-incubation of zolpidem (10 micro m) with varying concentrations of testosterone produced activation of biotransformation of zolpidem to its principal hydroxylated metabolite. Maximum activation was achieved at equimolar concentrations of testosterone (10 micro m). However, testosterone did not induce immunoactive CYP3A4 expression or catalytic function in cultured human hepatocytes. CONCLUSIONS: The increased Cmax and lower oral clearance of zolpidem in the elderly are consistent with recommendations of lower clinical doses of zolpidem in the elderly. Our clinical and in vitro data both suggest that reduced free serum testosterone may have a modulatory role in age-dependent changes in zolpidem pharmacokinetics in men.

Administration, Oral↗
PubMed2003

Insulin-like growth factor-1 and interleukin 6 predict sarcopenia in very old community-living men and women: the Framingham Heart Study.

OBJECTIVES: To assess the prognostic role of the inflammatory cytokine, interleukin 6 (IL-6), and insulin-like growth factor-1 (IGF-1) in predicting 2-year changes in fat-free mass (FFM) while controlling for potential confounders. DESIGN: Population-based cohort, the Framingham Heart Study, examined in 1992-93 and 1994-95. SETTING: General community. PARTICIPANTS: Two hundred thirty-two men and 326 women aged 72 to 92. MEASUREMENTS: IGF-1 was measured using radio-immunoassay and cellular IL-6 production using non-cross-reacting radioimmunoassays. FFM was estimated using population-specific equations for predicting FFM from bioelectrical impedance analysis developed separately for men and women. RESULTS: Higher IGF-1 predicted smaller loss of FFM in men than lower IGF-1 did (P=.002), after adjusting for age, baseline FFM, fat mass, and 2-year weight changes, whereas cellular IL-6 was a significant predictor of sarcopenia in women (P=.02). Weight change was a strong determinant of change in FFM in both sexes (P<.0001). CONCLUSION: Predictors of sarcopenia include body composition characteristics that are common to men and women and sex-specific metabolic predictors. Sarcopenia appears to reflect a withdrawal of anabolic stimuli, such as growth hormone, in men but an increase in catabolic stimuli, such as cellular IL-6, in women.

Adipose Tissue↗
PubMed2003

Sarcopenia: effects on body composition and function.

Sarcopenia is the loss of muscle mass that happens to everyone with age. However, the rate of sarcopenia and the severity of its sequelae vary greatly according to health status, physical activity, and possibly diet. In this review, I discuss the potential mechanisms of sarcopenia and some ideas about prevention and treatment.

Aging↗
PubMed2003

Plasma pyridoxal 5'-phosphate concentration is correlated with functional vitamin B-6 indices in patients with rheumatoid arthritis and marginal vitamin B-6 status.

Many patients with rheumatoid arthritis (RA) have low plasma pyridoxal-phosphate (PLP) but a normal erythrocyte aspartate aminotransferase activity coefficient (alpha EAST), a measure of vitamin B-6 status in the erythrocytes, compared with healthy subjects. The goal of the present study was to examine the correlations of PLP levels in these two compartments (plasma and erythrocytes) with other established indices of vitamin B-6 status, and to determine which indicator better reflects functional status of vitamin B-6 in patients with RA. Multiple indices of vitamin B-6 status were measured in 33 patients with RA. Plasma PLP, urinary 4-pyridoxic acid (4-PA), net increase in plasma total homocysteine after a methionine load (DeltatHcy) and net increase in urinary xanthurenic acid after a tryptophan load (DeltaXA) were log-transformed to reach normality for statistical analyses. We found that log-plasma PLP levels were inversely correlated with both log-DeltatHcy (r = -0.368, P = 0.035) and log-DeltaXA (r = -0.333, P = 0.05). Plasma PLP was not correlated with alpha EAST or urinary 4-PA excretion. In contrast, erythrocyte PLP was inversely correlated with alpha EAST (r = -0.431, P = 0.012) and positively correlated with log-4-PA (r = 0.475, P = 0.005), but erythrocyte PLP was not correlated with the outcomes of a methionine or tryptophan load test. Erythrocyte PLP and log-4-PA, but not plasma PLP, were correlated with dietary intake of vitamin B-6 after adjusting for protein intake (r = 0.420, P = 0.015 and r = 0.333, P = 0.05, respectively). We suggest that in patients with RA, plasma PLP levels are a better diagnostic indicator of functional vitamin B-6 status than erythrocyte PLP levels.

Adult↗
PubMed2003

Catabolism of aging: is it an inflammatory process?

PURPOSE OF REVIEW: Research in the field of sarcopenia is evolving rapidly, and the process is now recognized as an important cause of frailty and morbidity in the elderly. This review focuses on recent developments in the field, especially regarding the role of catabolic stimuli in causing sarcopenia. RECENT FINDINGS: There is now an impressive body of literature implicating increased interleukin-6 levels in successfully aging adults. New data indicate that high interleukin-6 levels carry a poor prognosis, although it is not clear if the cytokine has primarily a causal or counter-regulatory function. Interleukin-6 and other cytokines could function through direct catabolic effects, or by causing reduced dietary energy intake (the anorexia of aging), or by inducing insulin resistance or lowering growth hormone-insulin-like growth factor-I concentrations. Furthermore, apoptosis has now been linked to sarcopenia, suggesting that an inflammatory signal could trigger loss of muscle cells in the elderly even in the absence of overt inflammatory disease. SUMMARY: Aging causes loss of many of the anabolic signals to muscle that are present in young adulthood. Recent research suggests that there is also an increase in catabolic signals with age.

Aging↗
PubMed2003

Nutrition treatment for HIV wasting: a prescription for food as Medicine.

BACKGROUND: The optimal nutrition approach for the promotion of weight gain in HIV-infected adults with wasting remains unclear. Previous dietary interventions report minimal success and provide inadequate information regarding the counseling approach, contact time, session format, and issues addressed with the subject. The methods we report were incorporated in a 12-week intervention trial for the reversal of HIV-wasting. METHODS: All subjects involved in the intervention trial for the reversal of HIV-wasting received weekly, customized, one-on-one counseling and an oral nutrition supplement (480 kcal/d with 30 g protein). The nutrition aims were to (1) increase caloric intake to surpass daily energy requirements by 500 kcal/d (suggested caloric intake: 40 to 50 kcal/kg current weight); (2) increase protein intake (1.6 to 1.8 g/kg current weight per day); and (3) identify foods that may exacerbate or curtail side effects associated with HIV. Also assessed were preconceptions, nutrition knowledge level and primary information source, and obstacles to healthy eating. Sessions, conducted by a nutritionist in an interactive, action-oriented learning approach, ranged from 30 to 60 minutes. RESULTS: At baseline, subjects harbored many misconceptions, reported numerous HIV-related side effects, and lacked practical nutrition strategies, all of which interfered with weight maintenance and health. The protocol strategies were acceptable to the patients (87% subjects completed all visits), with marked improvements in dietary intake, weight, and body composition, both during and after intervention. CONCLUSIONS: We describe a customized nutrition intervention that produces changes in energy intake, maintenance of appropriate protein intake, and the reversal of unintentional weight loss over 5 to 15 months. Sustained improvements occurred across a socioeconomically diverse population, despite persistent disease- and medication-associated side effects.

Journal Article↗
PubMed2002

Cytokine responses differ by compartment and wasting status in patients with HIV infection and healthy controls.

Inflammatory cytokines are implicated in the loss of lean tissue that occurs in patients with inflammatory and infectious diseases, including HIV infection. However, it is not known whether plasma levels or cellular production of cytokines, or their antagonists, are more closely related to lean tissue loss. We studied whether plasma cytokine analysis could substitute for PBMC production assays in studies of nutrition status and disease state, and if cytokine antagonists could offer an alternative in assessing cytokine status. We used a bout of moderately difficult exercise to perturb cytokine production in 12 adults with HIV without wasting, 10 adults with HIV wasting, and nine healthy controls. Plasma and peripheral blood mononuclear cell (PBMC) production of interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra) and soluble TNF receptor type II (sTNFrII) were measured at baseline and 2, 6, 24 and 168h following exercise. PBMC production of IL-1beta, TNF-alpha and IL-6 were all higher in the HIV-infected patients without wasting than in the controls (P<0.05) or the patients with AIDS wasting (P<0.05). Plasma concentrations of TNF-alpha and IL-6 were higher in the HIV wasted patients than in the controls (P<0.05). Both plasma and PBMC levels of sTNFrII were higher in HIV patients, regardless of wasting, than in controls. These data suggest that the PBMC cytokine compartment is more sensitive to nutritional and metabolic abnormalities than is the plasma compartment. PBMC production of IL-1beta, IL-6 and TNF-alpha best distinguish between HIV patients with and without wasting, while plasma concentrations of IL-6 and TNF-alpha are elevated in AIDS wasting, but do not reliably distinguish patients with wasting from HIV-infected patients without wasting.

Adult↗
PubMed2002

Cachexia in rheumatoid arthritis is not explained by decreased growth hormone secretion.

OBJECTIVE: Patients with rheumatoid arthritis (RA) lose body cell mass (BCM) by unknown mechanisms. Since the loss of BCM in normal aging individuals parallels the characteristic age-related decline in growth hormone (GH) secretion, this study was carried out to determine whether further decreased GH secretion plays a role in the pathogenesis of this loss of BCM in RA patients, termed "rheumatoid cachexia." METHODS: GH secretory kinetics were determined by deconvolution analysis in 16 patients with RA and 17 healthy controls matched for age (mean +/- SD 45.4 +/- 13.2 years and 47.1 +/- 14.6 years, respectively), sex, race, and body mass index. Blood samples were obtained every 20 minutes for 24 hours. Body composition was ascertained using total-body potassium (TBK) as a measure of BCM and dual x-ray absorptiometry to determine fat mass. RESULTS: BCM was reduced in patients with RA compared with healthy controls (mean +/- SD gm TBK 79.5 +/- 9.5 versus 94.9 +/- 11.9; P < 0.0005), but there was no difference in fat mass. GH kinetic parameters in patients with RA did not differ from those in controls. CONCLUSION: These findings suggest that GH kinetics are unaltered in RA patients compared with healthy subjects; thus, GH deficiency does not account for rheumatoid cachexia.

Adult↗