Single muscle fiber physiology in neuromuscular disease.
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Biomedical subjects
Publications and source records attributed to Walter R Frontera.
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The general objective of the "Rehabilitation Medicine Summit: Building Research Capacity" was to advance and promote research in medical rehabilitation by making recommendations to expand research capacity. The five elements of research capacity that guided the discussions were: 1) researchers; 2) research culture, environment, and infrastructure; 3) funding; 4) partnerships; and 5) metrics. The 100 participants included representatives of professional organizations, consumer groups, academic departments, researchers, governmental funding agencies, and the private sector. The small group discussions and plenary sessions generated an array of problems, possible solutions, and recommended actions. A post-Summit, multi-organizational initiative is called for to pursue the agendas outlined in this report.
The general objective of the "Rehabilitation Medicine Summit: Building Research Capacity" was to advance and promote research in medical rehabilitation by making recommendations to expand research capacity. The five elements of research capacity that guided the discussions were 1) researchers; 2) research culture, environment, and infrastructure; 3) funding; 4) partnerships; and 5) metrics. The 100 participants included representatives of professional organizations, consumer groups, academic departments, researchers, governmental funding agencies, and the private sector. The small group discussions and plenary sessions generated an array of problems, possible solutions, and recommended actions. A post-Summit, multi-organizational initiative is called to pursue the agendas outlined in this report.
Muscle wasting accompanies aging and pathological conditions ranging from cancer, cachexia, and diabetes to denervation and immobilization. We show that activation of NF-kappaB, through muscle-specific transgenic expression of activated IkappaB kinase beta (MIKK), causes profound muscle wasting that resembles clinical cachexia. In contrast, no overt phenotype was seen upon muscle-specific inhibition of NF-kappaB through expression of IkappaBalpha superrepressor (MISR). Muscle loss was due to accelerated protein breakdown through ubiquitin-dependent proteolysis. Expression of the E3 ligase MuRF1, a mediator of muscle atrophy, was increased in MIKK mice. Pharmacological or genetic inhibition of the IKKbeta/NF-kappaB/MuRF1 pathway reversed muscle atrophy. Denervation- and tumor-induced muscle loss were substantially reduced and survival rates improved by NF-kappaB inhibition in MISR mice, consistent with a critical role for NF-kappaB in the pathology of muscle wasting and establishing it as an important clinical target for the treatment of muscle atrophy.
BACKGROUND AND PURPOSE: To evaluate the efficacy of supervised high-intensity progressive resistance training (PRT) on lower extremity strength, function, and disability in older, long-term stroke survivors. METHODS: Forty-two volunteers aged 50 years and above, 6 months to 6 years after a single mild to moderate stroke, were randomized into either a control group of upper extremity stretching or a PRT group that received a 12-week supervised high-intensity resistance training program consisting of bilateral leg press (LP), unilateral paretic and nonparetic knee extension (KE), ankle dorsiflexion (DF), and plantarflexion (PF) exercises. Functional performance was assessed using the 6-minute walk, stair-climb time, repeated chair-rise time, and habitual and maximal gait velocities. Self-reported changes in function and disability were evaluated using the Late Life Function and Disability Instrument (LLFDI). RESULTS: Single-repetition maximum strength significantly improved in the PRT group for LP (16.2%), paretic KE (31.4%), and nonparetic KE (38.2%) with no change in the control group. Paretic ankle DF (66.7% versus -24.0%), paretic ankle PF (35.5% versus -20.3%), and nonparetic ankle PF (14.7% versus -13.8%) significantly improved in the PRT group compared with the control. The PRT group showed significant improvement in self-reported function and disability with no change in the control. There was no significant difference between groups for any performance-based measure of function. CONCLUSIONS: High-intensity PRT improves both paretic and nonparetic lower extremity strength after stroke, and results in reductions in functional limitations and disability.
OBJECTIVE: To determine whether exercise training in combination with metformin improves cardiovascular risk indices and insulin in comparison to metformin alone among HIV-infected patients. METHODS AND DESIGN: We conducted a prospective, randomized, 3-month study of HIV patients on stable antiretroviral therapy with hyperinsulinemia and fat redistribution. Subjects received metformin alone or metformin and exercise training consisting of 1 h of aerobic and resistance training three times a week. Cardiovascular parameters, including blood pressure and endurance during sub-maximal stress testing, body composition, strength, insulin and other biochemical parameters were determined. RESULTS: Thirty-seven patients were randomized and 25 subjects completed the study. Subjects receiving exercise training and metformin demonstrated significant decreases in median waist-to-hip ratio [-0.02 (-0.06, -0.01) (median (interquartile range) versus -0.01 (0.03, 0.02), P = 0.026], resting systolic [-12 (-20, -4) versus 0 (-11, 11), P = 0.012] and diastolic blood pressures [-10 (-14, -8) versus 0 (-7, 8), P = 0.001], increased thigh muscle cross-sectional area [3 (-3, 12) versus -7 (-11, 0), P = 0.015], and improved exercise time [3 (0, 4) versus 0 (-1, 1), P = 0.045] compared with subjects receiving metformin alone. Fasting insulin and insulin area under the curve decreased significantly more in the exercise and metformin group (P < 0.05). Lipids and resting lactate did not change significantly between treatment groups. CONCLUSIONS: These data demonstrate that exercise training in combination with metformin significantly improves cardiovascular and biochemical parameters more than metformin alone in HIV-infected patients with fat redistribution and hyperinsulinemia. Combined treatment was safe, well tolerated and may be a useful strategy to decrease cardiovascular risk in this population.
OBJECTIVES: To study the effects of robotic rehabilitation in persons with chronic motor impairments after stroke and to examine whether improvements in motor abilities were sustained 4 months after the end of therapy. DESIGN: Pretest-posttest design. SETTING: Rehabilitation hospital, outpatient care. PARTICIPANTS: Volunteer sample of 42 persons with persistent hemiparesis from a single, unilateral stroke within the past 1 to 5 years. INTERVENTION: Robotic therapy for the paretic upper limb consisted of either sensorimotor active-assistive exercise, or progressive-resistive training during repetitive, planar reaching tasks, 3 times a week for 6 weeks. MAIN OUTCOME MEASURES: Modified Ashworth Scale, Fugl-Meyer Assessment (FMA), Motor Status Scale (MSS) score, and Medical Research Council motor power score. RESULTS: No significant differences were found among pretreatment clinical evaluations. Statistically significant gains from admission to discharge and from admission to follow-up (P<.05) were found on the FMA, MSS score for shoulder and elbow, and motor power score. CONCLUSIONS: Short-term, goal-directed robotic therapy can significantly improve motor abilities of the exercised limb segments in persons with chronic stroke that are sustained 4 months after discharge. This suggests that motor recovery can be enhanced by repetitive exercise training more than 1 year after stroke.
UNLABELLED: This focused review highlights the benefits of exercise and physical activity for community-dwelling older adults. It is part of the study guide on geriatric rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article specifically focuses on the benefits of physical activity and exercise for older adults with regard to morbidity, mortality, and disability. It discusses the appropriate preexercise screening and evaluation procedures for older adults contemplating exercise. Last, it reviews the current literature on the benefits of varying modes of exercise to modify the most prevalent chronic medical conditions of late life, including arthritis, heart disease, diabetes, stroke, pulmonary disease, and osteoporosis. OVERALL ARTICLE OBJECTIVE: To summarize the current knowledge regarding the therapeutic benefits of exercise for community-dwelling older adults.
BACKGROUND: An increased central distribution of fat with advancing age is associated with chronic metabolic and cardiovascular abnormalities. Little is known about the magnitude or pattern of fat distribution and its association with healthy aging. OBJECTIVE: This study describes approximately 10-y changes in body composition at 11 anthropometric sites in elderly persons and the metabolic and physical activity factors associated with these changes. DESIGN: Skinfold thicknesses, girths, body fat by hydrodensitometry, physical activity by questionnaire, and metabolic variables were examined twice, 9.4 +/- 1.4 y apart, in 54 men and 75 women aged 60.4 +/- 7.8 y at baseline. RESULTS: Subcutaneous fat declined (-17.2%; P < 0.001), whereas total fat mass increased (7.2%; P < 0.05). Waist and hip circumference changes were the best anthropometric predictors of total fat mass change (r(2) = 0.40-0.65, P < 0.0001). Thigh girth change was more strongly associated with fat-free mass change (r(2) = 0.22, P < 0.01) than with fat mass change (r(2) = 0.07, P < 0.05) in women. An increase in physical activity was associated with an attenuation of thigh girth decline in men and women (F ratio = 5.13, P < 0.007). Traditional metabolic markers of visceral adiposity (triacylglycerol, glucose, and total cholesterol) were not significantly related to the change in waist circumference. CONCLUSIONS: Skinfold thicknesses cannot be used to assess changes in body fat mass because of age-related fat redistribution. Higher levels of physical activity can attenuate the decline in appendicular lean tissue expected over 10 y. Waist and thigh girths, rather than skinfold thicknesses, should be considered for use in longitudinal studies in the elderly because the changes in these girths capture increased abdominal adiposity and sarcopenia, respectively.
BACKGROUND: The purpose of this study was to explore the relationship between muscle power output at different external resistances and performance of functional tasks. The authors hypothesized that power at 40% skeletal muscle 1 repetition maximum (1RM), in which contraction velocity is high, would explain more of the variability in tasks such as level walking than would peak power or 1RM strength, in which contraction velocity is lower. METHODS: Participants were men and women (n = 48; ages 65-91 years) with physical disability as evidenced by 2 or more deficits on the Medical Outcomes Study Short Form physical function subscale or a score of 9 or less on the Established Populations for the Epidemiologic Studies of the Elderly short physical performance battery. Muscle strength (1RM) was measured using a bilateral leg press exercise, and power output was determined by selecting the highest power output from 6 different contraction velocities: 40%, 50%, 60%, 70%, 80%, and 90% 1RM. Functional performance tasks consisted of habitual gait velocity (HGV) and stair climb (SC) and chair rise (CR) performance. Separate linear regression models were fit for each of the 3 dependent variables (SC, CR, HGV) using 1RM strength, power at 70% 1RM, and power at 40% 1RM as independent variables. All models were adjusted for age, body mass, and sex. RESULTS: Lower extremity power at 70% and 40% 1RM demonstrated greater associations with SC and HGV than did 1RM strength, whereas power at 40% 1RM demonstrated similar or stronger associations with all functional tasks compared with 1RM strength. Power at 40% 1RM explained the same or more of the variability in SC (R(2) = .42 [regression coefficient = -.169 +/- .06] vs .43 [-.206 +/- .071]), CR (R(2) = .28 [-.154 +/- .057] vs .24 [-.152 + .070]) and HGV (R(2) = .59 [.214 + .37] vs .51 [.223 +/- .049]) compared with power at 70% 1RM. Power at 40% 1RM explained more of the variability in the lower intensity (HGV) compared with the higher intensity (SC or CR) functions. CONCLUSIONS: Power output at 40% of 1RM explained more of the variability in HGV than did power at 70% 1RM, suggesting that measures such as HGV that require a lower percentage of maximal strength to perform might be more sensitive to differences in contraction velocity. Because HGV is highly predictive of subsequent disability, future studies should evaluate the determinants of muscle power output at low external resistances.
OBJECTIVE: This study examined whether incorporating progressive resistive training into robot-aided exercise training provides incremental benefits over active-assisted robot-aided exercise for the upper limb after stroke. DESIGN: A total of 47 individuals at least 1 yr poststroke were enrolled in this 6-wk training protocol. Paretic upper limb motor abilities were evaluated using clinical measures and a robot-based assessment to determine eligibility for robot-aided progressive resistive training at study entry. Subjects capable of participating in resistance training were randomized to receive either active-assisted robot-aided exercises or robot-aided progressive resistance training. Subjects who were incapable of participating in resistance training underwent active-assisted robotic therapy and were again screened for eligibility after 3 wks of robotic therapy. Those subjects capable of participating in resistance training at 3 wks were then randomized to receive either robot-aided resistance training or to continue with robot-aided active-assisted training. RESULTS: One subject withdrew due to unrelated medical issues, and data for the remaining 46 subjects were analyzed. Subjects in all groups showed improvement in measures of motor control (mean increase in Fugl-Meyer of 3.3; 95% confidence interval, 2.2-4.4) and maximal force (mean increase in maximal force of 3.5 N, P = 0.027) over the course of robot-aided exercise training. No differences in outcome measures were observed between the resistance training groups and the matched active-assisted training groups. Subjects' ability to perform the robotic task at the time of group assignment predicted the magnitude of the gain in motor control. CONCLUSION: The incorporation of robot-aided progressive resistance exercises into a program of robot-aided exercise did not favorably or negatively affect the gains in motor control or strength associated with this training, though interpretation of these results is limited by sample size. Individuals with better motor control at baseline experienced greater increases in motor control with robotic training.
OBJECTIVES: To evaluate a dynamic form of weighted vest exercise suitable for home use and designed to enhance muscle power, balance, and mobility. DESIGN: A single-blind, randomized, controlled trial. SETTING: Outpatient exercise research facility situated within an academic long-term care center. PARTICIPANTS: Twenty-one community-dwelling women aged 70 and older with a Short Physical Performance Battery (SPPB) score between 4 and 10 (out of 12). INTERVENTIONS: Subjects were randomized into a progressive resistance-training program using weighted vests for resistance with exercises designed to be specific to mobility tasks and have a component performed at the fastest possible velocity (Increased Velocity Exercise Specific to Task (InVEST), n=11) or a control exercise group (control, n=10), which performed slow-velocity, low-resistance exercise. Both groups exercised three times a week for 12 weeks. MEASUREMENTS: Changes in muscle power, balance, and physical performance were compared. RESULTS: In comparison to control group, InVEST group manifested significant improvements (P<.05) in leg power across measurements obtained at 75% to 90% of the one-repetition maximum. Both groups demonstrated significant improvements in chair stand and SPPB score from baseline, and the InVEST group showed significant improvements in gait speed and chair stand from baseline (P<.05). InVEST produced significantly greater changes in chair stand time than control (P<.05). CONCLUSION: InVEST training appears be an effective means of enhancing leg power and chair rise in this population and is worthy of further investigation as a means of enhancing balance and mobility.
Submovements are hypothesized building blocks of human movement, discrete ballistic movements of which more complex movements are composed. Using a novel algorithm, submovements were extracted from the point-to-point movements of 41 persons recovering from stroke. Analysis of the extracted submovements showed that, over the course of therapy, patients' submovements tended to increase in peak speed and duration. The number of submovements employed to produce a given movement decreased. The time between the peaks of adjacent submovements decreased for inpatients (those less than 1 month post-stroke), but not for outpatients (those greater than 12 months post-stroke) as a group. Submovements became more overlapped for all patients, but more markedly for inpatients. The strength and consistency with which it quantified patients' recovery indicates that analysis of submovement overlap might be a useful tool for measuring learning or other changes in motor behavior in future human movement studies.
The HIV-lipodystrophy syndrome is associated with fat redistribution and metabolic abnormalities, including insulin resistance (IR). The mechanisms and treatment strategies for IR in HIV-lipodystrophy are unclear, but data suggest that intramuscular lipids contribute to IR in this population. We previously showed that metformin and exercise improve hyperinsulinemia more than metformin alone in HIV-lipodystrophy. Now we investigate the effects of these treatment strategies on thigh muscle adiposity measured by computed tomography and additional body composition measures. Twenty-five HIV-infected patients on stable antiretroviral therapy with hyperinsulinemia and fat redistribution participated in a prospective, randomized, 3-month study of metformin alone or metformin and resistance training three times a week. Thigh muscle adiposity decreased significantly more as shown by increased muscle attenuation [2.0 (range, 0.5-5.0) vs. -1.0 (-3.5-0), P = 0.04] and sc leg fat tended to decrease more [-3.3 (-7.5-4.3) vs. 0.8 (-2.1-9.5), P = 0.06] in the combined treatment group in comparison with metformin alone. In multivariate analysis, change in thigh muscle adiposity remained a significant predictor of change in insulin (P = 0.04), controlling for changes in other body composition measurements. These data suggest that muscle adiposity, in addition to other fat depots, is an important determinant of hyperinsulinemia and that exercise has complex effects on regional fat depots in HIV-infected patients. Reduction in muscle adiposity may be an important mechanism by which exercise improves hyperinsulinemia in this population.
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.
OBJECTIVE: To examine whether robotic therapy can reduce motor impairment and enhance recovery of the hemiparetic arm in persons with chronic stroke. DESIGN: Pre-posttest design. SETTING: Rehabilitation hospital, outpatient care. PARTICIPANTS: Volunteer sample of 20 persons diagnosed with a single, unilateral stroke within the past 1 to 5 years, with persistent hemiparesis. INTERVENTIONS: Robotic therapy was provided 3 times weekly for 6 weeks. Subjects able to reach robot targets were randomly assigned to sensorimotor or progressive-resistive robotic therapy groups. Robotic therapy consisted of goal-directed, planar reaching tasks to exercise the hemiparetic shoulder and elbow. MAIN OUTCOME MEASURES: The Modified Ashworth Scale, Fugl-Meyer test of upper-extremity function, Motor Status Scale (MSS) score, and Medical Research Council motor power score. RESULTS: Evaluations by a single blinded therapist revealed statistically significant gains from admission to discharge (P<.05) on the Fugl-Meyer test, MSS score, and motor power score. Secondary analyses revealed group differences: the progressive-resistive therapy group experienced nonspecific improvements on wrist and hand MSS scores that were not observed in the sensorimotor group. CONCLUSIONS: Robotic therapy may complement other treatment approaches by reducing motor impairment in persons with moderate to severe chronic impairments.
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Smoothness is characteristic of coordinated human movements, and stroke patients' movements seem to grow more smooth with recovery. We used a robotic therapy device to analyze five different measures of movement smoothness in the hemiparetic arm of 31 patients recovering from stroke. Four of the five metrics showed general increases in smoothness for the entire patient population. However, according to the fifth metric, the movements of patients with recent stroke grew less smooth over the course of therapy. This pattern was reproduced in a computer simulation of recovery based on submovement blending, suggesting that progressive blending of submovements underlies stroke recovery.