Biomedical subjects

Frederick M Ivey

Publications and source records attributed to Frederick M Ivey.

12 recordsLinked to original sources

PubMed2007

Determinants of walking function after stroke: differences by deficit severity.

OBJECTIVES: To investigate the relationship of cardiovascular fitness (Vo(2)peak), neurologic deficits in balance and leg strength, and body composition to ambulatory function after stroke and to determine whether these relationships differ between those with milder versus more severe gait deficits. DESIGN: Cross-sectional correlation study. SETTING: Outpatient clinic of an academic medical center. PARTICIPANTS: Seventy-four people (43 men, 31 women; mean age +/- standard deviation, 64+/-10y) with chronic hemiparetic stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Thirty-foot (9.1-m) walk velocity, 6-minute walk distance, Vo(2)peak, Berg Balance Scale score, bilateral quadriceps eccentric torque, total and regional lean mass, and percentage of fat mass. RESULTS: Short-distance walking correlated significantly with cardiovascular fitness, balance, paretic leg strength, nonparetic leg strength, percentage of body fat, and paretic lean mass but not with nonparetic lean mass. Long-distance walking correlated significantly with cardiovascular fitness, balance, paretic leg strength, nonparetic leg strength, and paretic lean mass but not with percentage of body fat or nonparetic lean mass. Stepwise regression showed that cardiovascular fitness, balance, and paretic leg strength were independently associated with long-distance walking (r(2)=.60, P<.001). Variance in long-distance walking was largely explained by balance for those who walked more slowly (<.48m/s) for short distances (r(2)=.42, P<.001) and by cardiovascular fitness for those who walked more quickly (>.48m/s) for short distances (r(2)=.26, P=.003). CONCLUSIONS: Short-distance walking after stroke is related to balance, cardiovascular fitness, and paretic leg strength. Long-distance walking ability differs by gait deficit severity, with balance more important in those who walk more slowly and cardiovascular fitness playing a greater role in those who walk more quickly. Improved understanding of the factors that predict ambulatory function may assist the design of individualized rehabilitation strategies across the spectrum of gait deficit severity in those with hemiparetic stroke.

Adult↗

PubMed2006

High prevalence of abnormal glucose metabolism and poor sensitivity of fasting plasma glucose in the chronic phase of stroke.

BACKGROUND: Cardiovascular disease is the leading cause of death in long-term stroke survivors, and whole-body glucose metabolism is strongly linked to cardiovascular disease risk. This study provides important preliminary information on the prevalence of abnormal glucose metabolism in chronic stroke patients (mean 3 years after stroke) and reports on the utility of screening for abnormalities using fasting plasma glucose (FPG) in this population. METHODS: Two hundred and sixteen chronic hemiparetic stroke patients were screened for diabetes status by medical history and FPG. A subset (n = 80) was evaluated by oral glucose tolerance test to assess the utility of screening for abnormalities using FPG alone. RESULTS: Seventy-five of the 216 (35%) had type 2 diabetes by medical history. Another 70 were either diabetic (n = 11) or had impaired fasting glucose (n = 59) based on a single blood draw at the time of screening. FPG among non-diabetic stroke patients had a sensitivity of 49% for predicting abnormalities in the 2-hour glucose level during oral glucose tolerance test. Cumulative results identify 77% as abnormal (impaired or diabetic) on the basis of medical history, fasting plasma glucose, and/or 2-hour glucose level. CONCLUSIONS: The prevalence of abnormal glucose metabolism is extremely high in chronic stroke and is underestimated on the basis of FPG.

Aged↗

PubMed2006

Age and sex affect human muscle fibre adaptations to heavy-resistance strength training.

This study assessed age and sex effects on muscle fibre adaptations to heavy-resistance strength training (ST). Twenty-two young men and women (20-30 years old) and 18 older men and women (65-75 years old) completed 9 weeks of heavy-resistance knee extension exercises with the dominant leg 3 days week(-1); the non-dominant leg served as a within-subject, untrained control. Bilateral vastus lateralis muscle biopsies were obtained before and after ST for analysis of type I, IIa and IIx muscle fibre cross-sectional area (CSA) and fibre type distribution. One-repetition maximum (1-RM) strength was also assessed before and after ST. ST resulted in increased CSA of type I, IIa and IIx muscle fibres in the trained leg of young men, type I and IIa fibres in young women, type IIa fibres in older men, and type IIx fibres in older women (all P<0.05). Analysis of fibre type distribution revealed a significant increase in the percentage of type I fibres (P<0.05) along with a decrease in type IIx fibres (P=0.054) after ST only in young women. There were no significant changes in muscle fibre CSA or fibre type distribution in the untrained leg for any group. All groups displayed significant increases in 1-RM (27-39%; all P<0.01). In summary, ST led to significant increases in 1-RM and type II fibre CSA in all groups; however, age and sex influence specific muscle fibre subtype responses to ST.

Adaptation, Physiological↗

PubMed2006

Exercise rehabilitation after stroke.

Stroke is a leading cause of disability that results not only in persistent neurological deficits, but also profound physical deconditioning that propagates disability and worsens cardiovascular risk. The potential for exercise-mediated adaptations to improve function, fitness, and cardiovascular health after stroke has been underestimated: it represents an emerging arena in neurotherapeutics. To define the health rationale for cardiovascular (aerobic) exercise, we first outline the impact of debilitating secondary biological changes in muscle and body composition on fitness and metabolic health after stroke. We provide an overview of evidence-based advances in exercise therapeutics, with a focus on task-oriented models that combine a progressive aerobic conditioning stimulus with motor learning to improve multiple physiological domains that determine longitudinal outcomes after stroke. Although progress in development of safe and effective exercise strategies is advancing, fundamental questions regarding dose intensity, prescription to optimize central and peripheral neuromuscular adaptations, and the public health value of exercise in secondary stroke prevention remain unanswered. Key issues steering future research in exercise neurotherapeutics are discussed within the context of initiatives to facilitate translation to community-based studies, requisite for dissemination.

Adaptation, Physiological↗

PubMed2005

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 (3x/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%, delta% 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.

Aged↗

PubMed2005

Elevated tumor necrosis factor-alpha in skeletal muscle after stroke.

BACKGROUND AND PURPOSE: Tumor necrosis factor-alpha (TNF-alpha), an inflammatory cytokine negligibly expressed in normal muscle, is elevated in selected metabolic conditions characterized by muscle wasting and insulin resistance. Inflammation is fundamental to stroke pathogenesis. Stroke patients have gross muscular atrophy and high prevalence of diabetes and insulin resistance. Yet, no previous studies examined TNF-alpha expression in hemiparetic skeletal muscle. This study investigates whether TNF-alpha mRNA levels are elevated in paretic compared with nonparetic leg muscles of chronic ischemic stroke patients and age-matched controls. METHOD: Total RNA extracted from bilateral vastus lateralis muscle biopsies from n=20 hemiparetic stroke patients and n=9 healthy controls was reverse transcribed to cDNA, then TNF-alpha transcripts were amplified by real-time quantitative polymerase chain reaction. TNF-alpha mRNA concentrations were normalized against acidic ribosomal phosphoprotein, housekeeping gene. RESULTS: TNF-alpha mRNA levels were 2.8-fold higher in paretic compared with control leg muscle (6.28+/-1.86 versus 2.28+/-0.67; P<0.03) and 1.6-fold higher in nonparetic leg (3.71+/-1.02; P<0.11) compared with controls. There was a trend for higher TNF-alpha mRNA in paretic compared with nonparetic leg. CONCLUSIONS: Findings demonstrate increased TNF-alpha expression in paretic leg muscle, suggesting inflammatory pathways are accelerated in stroke muscle. Further studies are under way to determine whether intramuscular TNF-alpha contributes to atrophy and metabolic abnormalities after stroke.

Aged↗

PubMed2004

Unilateral impairment of leg blood flow in chronic stroke patients.

BACKGROUND: Previous studies comparing paretic limb blood flow with the unaffected limb have been contradictory and have often omitted comparisons of peak reactive hyperemic flow. Our objective was to perform bilateral measurements of resting and reactive hyperemic blood flow in the lower legs of chronic (>6 months) stroke patients. A secondary purpose was to determine the extent to which any unilateral changes in limb blood flow were a function of decreases in lean tissue mass on the affected side. We hypothesized that the chronic hemiparesis accompanying ischemic stroke creates an altered metabolic environment in the tissues of the affected side that ultimately impairs vasomotor function. METHODS: The study used a single-visit cross-sectional design. All tests were performed at the Baltimore VA Medical Center. Nineteen chronic hemiparetic stroke patients (15 male, 4 female) who had mild to moderate hemiparetic gait after ischemic stroke were recruited for observation. Bilateral measurements of resting and reactive hyperemic blood flow were made using venous occlusion strain gauge plethysmography. Paired t-tests were used for the between leg comparison. Regression analysis and analysis of covariance were utilized to determine the strength of the relationship between lower leg lean tissue mass and blood flow. RESULTS: Resting and reactive hyperemic blood flows were significantly reduced in the paretic compared with the non-paretic limb (32 and 35%, respectively, p < 0.001). Lean tissue mass was also significantly lower in the affected limb (p < 0.01). However, neither resting nor reactive hyperemic blood flows were significantly correlated with lower leg lean tissue mass by dual energy X-ray absorptiometry. The difference in blood flow between limbs remained after covarying for lean tissue mass. CONCLUSION: Hemiparesis causes impairments in vasomotor function under both resting and hyperemic conditions that are independent of the muscle atrophy on the affected side.

Absorptiometry, Photon↗

PubMed2004

Muscle molecular phenotype after stroke is associated with gait speed.

The disability of patients after stroke is generally attributed to upper motor neuron defects, but secondary changes in paretic muscle may enhance the disability. We analyzed the molecular phenotype and metabolic profile of the paretic and nonparetic vastus lateralis (VL) and we measured the severity of gait deficit in 13 patients at least 6 months after ischemic stroke. The results showed a significant increase in the proportion of fast myosin heavy chain (MHC, 68 +/- 14%) in the paretic compared to the nonparetic VL (50 +/- 13%). The specific activity of citrate synthase and glyceraldehyde phosphodehydrogenase was not significantly different between the two sides. The proportion of fast MHC was inversely associated with severity of gait deficit indexed by self-selected walking speed in the paretic leg, but not the nonparetic leg. Our findings demonstrate significant and potentially modifiable secondary biologic changes in hemiparetic muscle phenotype that may contribute to the disability of stroke.

Aged↗

PubMed2003

Reliability of treadmill exercise testing in older patients with chronic hemiparetic stroke.

OBJECTIVE: To assess the test-retest reliability of cardiopulmonary measurements during peak effort and submaximal treadmill walking tests in older patients with gait-impaired chronic hemiparetic stroke. DESIGN: Nonrandomized test-retest. SETTING: Hospital geriatric research stress testing laboratory. PARTICIPANTS: Fifty-three subjects (44 men, 9 women; mean age, 65+/-8y) with chronic hemiparetic gait after remote (>6mo) ischemic stroke. Patients had mild to moderate chronic hemiparetic gait deficits, making handrail support necessary during treadmill walking. INTERVENTIONS: Peak effort and submaximal effort treadmill walking tests were conducted and then repeated on a separate day at least a week later. Main outcome measures Reliability coefficients (r) were calculated for heart rate, systolic blood pressure (SBP), oxygen consumption (Vo(2) [L/min]), Vo(2) (mL.kg(-1).min(-1)), respiratory exchange ratio (RER), rate-pressure product (RPP), and oxygen pulse during peak effort testing. The reliability coefficients for all but SBP and RPP data were calculated from the submaximal tests. RESULTS: Heart rate (r=.87), Vo(2)peak (L/min) (r=.92), Vo(2)peak (mL.kg(-1).min(-1)) (r=.92), and oxygen pulse (r=93) were highly reliable parameters during maximal testing in this population. Submaximal testing produced highly reliable results for V.o(2) (L/min) (r=.89) and oxygen pulse (r=.85). All cardiopulmonary measures except RER had a reliability coefficient greater than.80 during submaximal testing in this population. CONCLUSION: Our study provides the first evidence that peak effort treadmill testing provides highly reliable oxygen consumption measures in chronic hemiparetic stroke patients using minimal handrail support. The submaximal tests were at or near the threshold level of reliability for the 2 most important measures of V.o(2) (L/min) and V.o(2) (mL.kg(-1).min(-1)) (r=.89, r=.84, respectively), with the remaining measures falling above.70.

Adult↗

PubMed2003

A single bout of walking exercise enhances endogenous fibrinolysis in stroke patients.

PURPOSE: Impaired endogenous fibrinolysis is an important predictor for increased risk of stroke and myocardial infarction. Acute exercise can enhance fibrinolysis, primarily by stimulating short-term increases in plasma tissue plasminogen activator (tPA), which is postulated to protect against atherothrombotic events. No prior studies have examined the fibrinolytic response to exercise in stroke survivors despite their high risk for recurrent stroke and myocardial infarction. The purpose of this study was to assess the fibrinolytic response to acute submaximal exercise in chronic hemiparetic stroke patients. METHODS: Eighteen (16 men, 2 women) untrained stroke patients with chronic hemiparetic gait deficits volunteered for participation in this single session exercise study. Fasting blood samples for determination of tPA and plasminogen activator inhibitor (PAI-1) enzyme activities were obtained before, immediately after, and 60 min after submaximal treadmill walking. Patients walked at 60% maximal heart rate reserve (low-moderate intensity) for a cumulative total of 20 min. RESULTS: The exercise bout increased tPA activity by 79% (P < 0.01) and decreased PAI-1 activity by 18% (P < 0.01). At 1 h after completing the walking exercise, plasma tPA activity levels were still significantly elevated (43%,P < 0.01), and PAI-1 activity levels were 25% lower (P < 0.01) than baseline. CONCLUSIONS: These findings demonstrate that a single bout of aerobic walking exercise can improve fibrinolysis profiles in chronic stroke patients. Significant increases in endogenous tPA and reductions in PAI-1 activity persist for at least 1 h after exercise cessation. The implications are that alterations in physical activity during the day may modify clot lysing potential, thereby affecting atherothrombotic risk.

Aged↗

PubMed2002

Reduced thrombomodulin in human peripheral nerve microvasculature.

Thrombomodulin (TM), a vascular endothelial receptor, terminates the actions of thrombin and accelerates activated protein C formation. TM is ubiquitous throughout the systemic microcirculation but is reduced in brain regions predisposed to lacunar infarction. We investigated whether TM is present within human nerve and differentially expressed according to vessel caliber and proximity to the blood-nerve barrier. Vascular endothelial TM was detected on sural nerve biopsies with immunohistochemistry. The proportion of TM-positive microvessels was expressed relative to total von Willebrand factor (vWF)-positive vessels. Although vWF was detectable in all microvessels, TM expression was absent from the perineurial vessels. TM was detected in 47% (15-80%, 95% confidence level) of larger epineurial arterioles, in 43% (30-61%) of smaller epineurial vessels, and in 30% (19-47%) of endoneurial vessels. These findings demonstrate that TM is present in human nerve microvasculature but is regionally deficient in proximity to the blood-nerve barrier, which may predispose nerve to microvascular ischemia in inflammatory/prothrombotic conditions.

Biopsy↗

PubMed2002

Thrombomodulin deficiency in human diabetic nerve microvasculature.

Human diabetic neuropathy is multifactorial in etiology, with ischemia as a final common pathology. Although impaired vascular endothelial cell function in diabetic microvascular injury is established, the role of thrombomodulin (TM)-dependent protein C antithrombotic mechanism in the pathogenesis of neuropathy is unclear. This neuropathologic case-control study investigated whether vascular endothelial TM expression is deficient in peripheral nerve microvessels in diabetic neuropathy. Sural nerve biopsies from 7 patients with diabetic neuropathy and 10 with axonal neuropathy without vasculopathy were immunostained with anti-TM and anti-von Willebrand factor (vWF; an endothelial cell marker) antibodies. The proportion of TM-positive microvessels was expressed relative to total vWF-staining vessels, according to vessel caliber and regional distribution within the nerve. In diabetic nerves compared with reference controls, the proportion of TM-positive endoneurial microvessels was 15-fold lower (0.02 vs. 0.30 in diabetic nerves vs. controls, P < 0.004), and the proportion of small-caliber epineurial microvessels was 10-fold lower (0.04 vs. 0.43, P < 0.001). No TM expression was detected at the perineurium in diabetic or control nerves. We demonstrate a substantial reduction of vascular endothelial TM expression throughout human diabetic neuropathy. These findings suggest that an impaired native TM-dependent protein C antithrombotic mechanism may contribute to microvascular ischemia in the pathogenesis of diabetic neuropathy.

Adult↗