Andrew P. Goldberg

Treadmill Exercise Rehabilitation Improves Ambulatory Function and Cardiovascular Fitness in Patients With Chronic Stroke A Randomized, Controlled Trial

Background and Purpose— Physical inactivity propagates disability after stroke through physical deconditioning and learned nonuse. We investigated whether treadmill aerobic training (T-AEX) is more effective than conventional rehabilitation to improve ambulatory function and cardiovascular fitness in patients with chronic stroke. Methods— Sixty-one adults with chronic hemiparetic gait after ischemic stroke (>6 months) were randomized to 6 months (3×/week) progressive T-AEX or a reference rehabilitation program of stretching plus low-intensity walking (R-CONTROL). Peak exercise capacity (Vo2 peak), o2 consumption during submaximal effort walking (economy of gait), timed walks, Walking Impairment Questionnaire (WIQ), and Rivermead Mobility Index (RMI) were measured before and after 3 and 6 months of training. Results— Twenty-five patients completed T-AEX and 20 completed R-CONTROL. Only T-AEX increased cardiovascular fitness (17% versus 3%, &dgr;% T-AEX versus R-CONTROL, P<0.005). Group-by-time analyses revealed T-AEX improved ambulatory performance on 6-minute walks (30% versus 11%, P<0.02) and mobility function indexed by WIQ distance scores (56% versus 12%, P<0.05). In the T-AEX group, increasing training velocity predicted improved Vo2 peak (r=0.43, P<0.05), but not walking function. In contrast, increasing training session duration predicted improved 6-minute walk (r=0.41, P<0.05), but not fitness gains. Conclusions— T-AEX improves both functional mobility and cardiovascular fitness in patients with chronic stroke and is more effective than reference rehabilitation common to conventional care. Specific characteristics of training may determine the nature of exercise-mediated adaptations.

Acute-Phase Serum Amyloid A: An Inflammatory Adipokine and Potential Link between Obesity and Its Metabolic Complications

Background Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD). However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood. Methods and Findings Acute-phase serum amyloid A (A-SAA) mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index ( r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively). Serum A-SAA levels decreased significantly after weight loss in obese participants ( p = 0.006), as well as in those treated with rosiglitazone ( p = 0.033). The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA ( r = −0.74; p = 0.034). SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL)-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%. Conclusions A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements in systemic inflammation and insulin resistance with weight loss and rosiglitazone therapy may in part be mediated by decreases in adipocyte A-SAA production.

Exercise rehabilitation improves functional outcomes and peripheral circulation in patients with intermittent claudication: a randomized controlled trial.

OBJECTIVE: To determine the effects of a 6‐month exercise program on ambulatory function, free‐living daily physical activity, peripheral circulation, and health‐related quality of life (QOL) in disabled older patients with intermittent claudication.

Aerobic versus strength training for risk factor intervention in middle-aged men at high risk for coronary heart disease☆

To compare the effects of strength training (ST) to those of aerobic training (AT) for coronary heart disease (CHD) risk factor intervention, we studied 37 previously untrained males (aged 50 +/- 9 years, mean +/- SD) before and after 20 weeks of either ST (N = 14), AT (walk/jog, N = 13), or no exercise (inactive controls, N = 10). Lipoprotein and lipid profiles, blood pressure, and glucose and insulin responses to an oral glucose tolerance test (OGTT) were assessed before and after the training period in all three groups. The ST program produced significant reductions in plasma glucose levels at 60, 90, and 120 minutes (P < .05) after glucose ingestion, whereas the AT program resulted in significant reductions only at 90 and 120 minutes (P < .05). ST also decreased insulin levels during fasting (P < .05) and at 90 and 120 minutes (P < .01) after glucose ingestion. AT decreased insulin levels at 90 and 120 minutes (P < .01) after glucose ingestion. Both training programs reduced the total area under the glucose tolerance curve for glucose (both P < .05) and insulin (both P < .05), but there were no significant differences in these changes between the two groups. None of the glucose or insulin values were significantly altered in the control group. There were no significant changes in lipoprotein and lipid profiles or blood pressure in any of the three groups. These results suggest that ST and AT have comparable effects on risk factors for CHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Treadmill Exercise Activates Subcortical Neural Networks and Improves Walking After Stroke A Randomized Controlled Trial

Background and Purpose— Stroke often impairs gait thereby reducing mobility and fitness and promoting chronic disability. Gait is a complex sensorimotor function controlled by integrated cortical, subcortical, and spinal networks. The mechanisms of gait recovery after stroke are not well understood. This study examines the hypothesis that progressive task-repetitive treadmill exercise (T-EX) improves fitness and gait function in subjects with chronic hemiparetic stroke by inducing adaptations in the brain (plasticity). Methods— A randomized controlled trial determined the effects of 6-month T-EX (n=37) versus comparable duration stretching (CON, n=34) on walking, aerobic fitness and in a subset (n=15/17) on brain activation measured by functional MRI. Results— T-EX significantly improved treadmill-walking velocity by 51% and cardiovascular fitness by 18% (11% and −3% for CON, respectively; P<0.05). T-EX but not CON affected brain activation during paretic, but not during nonparetic limb movement, showing 72% increased activation in posterior cerebellar lobe and 18% in midbrain (P<0.005). Exercise-mediated improvements in walking velocity correlated with increased activation in cerebellum and midbrain. Conclusions— T-EX improves walking, fitness and recruits cerebellum-midbrain circuits, likely reflecting neural network plasticity. This neural recruitment is associated with better walking. These findings demonstrate the effectiveness of T-EX rehabilitation in promoting gait recovery of stroke survivors with long-term mobility impairment and provide evidence of neuroplastic mechanisms that could lead to further refinements in these paradigms to improve functional outcomes.

Resistive training can reduce coronary risk factors without altering VO2max or percent body fat.

Eleven healthy, untrained males (age = 44 +/- 1 yr; range = 40 to 55 yr) were studied to determine the effects of 16 wk of high-intensity resistive training on risk factors for coronary artery disease. Lipoprotein-lipid profiles, plasma glucose and insulin responses during an oral glucose tolerance test, and blood pressure at rest were determined before and after training. The training program resulted in a 13% increase in high-density lipoprotein-cholesterol (39 +/- 2 vs 44 +/- 3 mg.dl-1, P less than 0.05), a 43% increase in high-density lipoprotein-cholesterol (7 +/- 2 vs 10 +/- 2 mg.dl-1, P less than 0.05), a 5% reduction in low-density lipoprotein cholesterol (129 +/- 5 vs 122 +/- 5 mg.dl-1, P less than 0.05), and an 8% decrease in the total cholesterol/high-density lipoprotein-cholesterol ratio (5.1 +/- 0.3 vs 4.7 +/- 0.3, P less than 0.01), despite no changes in VO2max, body weight, or percent body fat. Glucose-stimulated plasma insulin concentrations during oral glucose tolerance testing were significantly lower, and supine diastolic blood pressure was reduced (P less than 0.05) as a result of the training program. No changes in any of these variables occurred in a sedentary control group. These findings indicate that resistive training can lower risk factors for coronary artery disease independent of changes in VO2max, body weight, or body composition.

Weight control self-efficacy types and transitions affect weight-loss outcomes in obese women☆

Matching obesity treatments to heterogeneous clients is a recent evolution in the development of more effective weight-control programs, yet most interventions emphasize the external features of treatments rather than the internal belief structures of individuals. The purpose of this study was to determine whether Q methodology would identify distinct types of weight-control self-efficacy beliefs in obese women that would be linked to outcomes of a weight-loss program. Fifty-four women (45 +/- 9 yrs, Mean +/- SD) 136 +/- 10% over ideal body weight participated in a 9-month nutritional/behavioral weight loss program. Two major self-efficacy categories emerged through factor analysis of Q sorts: assureds and disbelievers. The assureds (n = 28) had the strongest self-efficacy beliefs and at baseline reported significantly (p < .01) greater self-esteem and less depression than the disbelievers (n = 26). By posttreatment, the assureds had lost significantly more weight (10 +/- 6 vs. 7 +/- 7 kg). Regrouping the data for analysis by posttreatment self-efficacy types demonstrated transitions in the self-efficacy beliefs of the women during treatment. Those who were disbelievers at baseline but became assureds posttreatment (n = 7) lost twice as much weight as the women who started and finished as disbelievers (n = 19) (10 +/- 7 kg vs. 5 +/- 5 kg). The posttreatment assureds (n = 32) lost significantly more weight than the disbelievers (n = 22) (10 +/- 6 vs. 6 +/- 5 kg), and reported better self esteem, mood, and eating patterns. Thus, assessment of intrinsic belief systems, particularly weight-control self-efficacy, may provide new directions for designing interventions that target distinctly different needs of obese women to affect greater weight loss and more positive affective states.

Exercise training reduces coronary risk and effectively rehabilitates hemodialysis patients

This study examines the effects of 12 months of endurance exercise training (cycling, walking and jogging) on lipid profiles, glucose metabolism, blood pressure, anemia and psychological function in 14 hemodialysis patients. Maximal aerobic capacity (VO2max) increased 18% in the exercisers (p less than 0.01), but did not change in 11 controls. This was associated with a reduction in depression, a decrease in dosages of antihypertensive medications, a significant increase in hematocrit and hemoglobin levels (red cell mass rose, plasma volume did not change), a decrease in plasma triglyceride by 23% (p less than 0.05) and an increase in high-density lipoprotein cholesterol (HDL-C) levels by 21% (p less than 0.01) (both HDL-C and triglyceride levels worsened in the sedentary controls), and an 18% increase in glucose disappearance rates (p less than 0.05) in spite of a 52% decrease in fasting insulin levels (p less than 0.01), suggesting that insulin sensitivity improved. These results demonstrate that some of the complications present in hemodialysis patients may be caused by their sedentary life-style, rather than endstage renal disease itself. This suggests that rehabilitation through exercise is possible for these patients. By reducing coronary risk factors in hemodialysis patients, exercise training may also decrease their heightened morbidity and mortality from atherosclerotic complications. These possibilities need to be examined in a longitudinal study.

Insulin Resistance, Elevated Glomerular Filtration Fraction, and Renal Injury

The development of insulin resistance may be an early step in the development of hypertension; however, the mechanism for this process is not known. The worsening of insulin resistance and hypertension could increase both systemic and glomerular capillary pressures and predispose an individual to renal injury. The purpose of this study was to examine the relationship of insulin resistance to glomerular hemodynamics and dietary salt intake in 10 older (68 +/- 6 years), obese (body mass index, 31 +/- 4 kg/m2), mildly hypertensive (151 +/- 8/82 +/- 2 mm Hg), sedentary subjects without clinical evidence of diabetes or renal disease. They were studied on separate days with radioisotopic renal clearances (glomerular filtration rate by 99mTc-diethylenetriaminepentaacetic acid urinary clearance; renal plasma flow by 131I-hippuran serum disappearance) and a two-dose (40 and 100 mU/m2 per minute) hyperinsulinemic euglycemic clamp for measurement of glucose disposal after 2 weeks of a 3-g and 2 weeks of a 10-g sodium diet. Glomerular filtration rate (68.1 +/- 7.7 to 78.0 +/- 6.6 mL/min per 1.73 m2, P = .08) and glomerular filtration fraction (0.21 +/- 0.02 to 0.22 +/- 0.02, P = .5) did not change significantly after dietary salt was increased. During low dietary salt intake, there was an inverse relationship between glomerular filtration fraction and glucose disposal rate (milligrams per kilogram fat-free mass per minute) at both low (r = -.70, P = .04) and high (r = -.83, P = .006) insulin levels. However, these relationships were attenuated during salt loading. This suggests that a greater degree of insulin resistance, not increased dietary salt, may predispose older mildly hypertensive subjects to renal injury by worsening renal hemodynamics through the elevation of glomerular filtration fraction and resultant glomerular hyperfiltration.

Comparing brain activation associated with isolated upper and lower limb movement across corresponding joints

It was shown recently that functional activation across brain motor areas during locomotion and foot movements are similar but differ substantially from activation related to upper extremity movement (Miyai [ 2001 ]: Neuroimage 14:1186–1192). The activation pattern may be a function of the behavioral context of the movement rather than of its mechanical properties. We compare motor system activation patterns associated with isolated single‐joint movement of corresponding joints in arm and leg carried out in equal frequency and range. Eleven healthy volunteers underwent BOLD‐weighted fMRI while performing repetitive elbow or knee extension/flexion. To relate elbow and knee activation to the well‐described patterns of finger movement, serial finger‐to‐thumb opposition was assessed in addition. After identifying task‐related voxels using statistical parametric mapping, activation was measured in five regions of interest (ROI; primary motor [M1] and somatosensory cortex [S1], premotor cortex, supplementary motor area [SMA] divided into preSMA and SMA‐proper, and cerebellum). Differences in the degree of activation across ROIs were found between elbow and knee movement. SMA‐proper activation was prominent for knee, but almost absent for elbow movement (P < 0.05); finger movement produced small but constant SMA‐proper activation. Ipsilateral M1 activation was detected during knee and finger movement, but was absent for the elbow task (P < 0.05). Knee movement showed less lateralization in M1 and S1 than other tasks (P < 0.05). The data demonstrate that central motor structures contribute differently to isolated elbow and knee movement. Activation during knee movement shows similarities to gait‐related activation patterns. Hum. Brain Mapping 17:131–140, 2002.