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Biomedical subjects

Richard F Macko

Publications and source records attributed to Richard F Macko.

31 records · Page 2Linked to original sources

Improved hemiparetic muscle activation in treadmill versus overground walking.

OBJECTIVE: Treadmill training is a promising tool for retraining gait after stroke. The treadmill induces an immediate shift toward symmetry and longer paretic stance times due to altered muscle activation (active) or the motorized belt (passive). The authors investigated vastus lateralis and medial hamstrings activation differences between treadmill and overground walking in participants with stroke. METHODS: Vastus lateralis and medial hamstrings surface electromyography was recorded during velocity-matched overground and treadmill walking in 19 chronically hemiparetic subjects. Variables from ensemble averages of electromyography included burst onset and offset times (% cycle), duration (% cycle), integrated amplitude (mV.% cycle), and onset relative to foot strike (% cycle). Conditions were compared using paired t-tests (alpha = 0.05). RESULTS: Paretic vastus lateralis onset occurred earlier in the treadmill condition (overground: 47.1%, treadmill: 41.9%, P = 0.01). For nonparetic vastus lateralis in the treadmill condition, onset occurred later (overground: 85.2%, treadmill: 87.6%, P = 0.09), offset occurred earlier (overground: 54.7%, treadmill: 47.8%, P = 0.03), duration was shorter (overground: 69.1%, treadmill: 61.2%, P = 0.01), and integrated amplitude was lower (overground: 14.1, treadmill: 10.6, P = 0.05). Within limbs, paretic vastus lateralis onset occurred earlier relative to paretic foot strike. Nonparetic vastus lateralis onset occurred later relative to nonparetic foot strike. CONCLUSIONS: Treadmill walking induces immediate changes in vastus lateralis, but not medial ham-strings, activation patterns. These alterations (earlier paretic vastus lateralis onset and later nonparetic vastus lateralis onset) during treadmill versus overground walking parallel the increased symmetry in gait patterning.

Electromyography↗

Acquired immunodeficiency syndrome and the risk of stroke.

BACKGROUND AND PURPOSE: Although acquired immunodeficiency syndrome (AIDS) is thought to increase the risk of stroke, few data exist to quantify this risk. This is the first population-based study to quantify the AIDS-associated risk of stroke. METHODS: We identified all incident ischemic stroke (IS) and intracerebral hemorrhage (ICH) cases among young adults 15 to 44 years of age in central Maryland and Washington, DC, who were discharged from any of the 46 hospitals in the study area in 1988 and 1991. Using data from the medical records, 2 neurologists reviewed each case to confirm the diagnosis. Cases of AIDS among these patients with stroke were defined using Centers for Disease Control and Prevention criteria (1987). The number of cases of AIDS in the central Maryland and Washington population during 1988 and 1991 was determined from regional health departments working with the Centers for Disease Control and Prevention. Poisson regression was used to estimate the age-, race-, and sex-adjusted relative risk of stroke associated with AIDS. RESULTS: There were 385 IS cases (6 with AIDS) and 171 ICH cases (6 with AIDS). The incidences of IS and ICH among persons with AIDS were both 0.2% per year. AIDS conferred an adjusted relative risk of 13.7 (95% confidence interval [CI], 6.1 to 30.8) for IS and 25.5 (95% CI, 11.2 to 58.0) for ICH. After exclusion of 5 cases of stroke in AIDS patients in whom other potential causes were identified, AIDS patients continued to have an increased risk of stroke with an adjusted relative risk of 9.1 (95% CI, 3.4 to 24.6) for IS and 12.7 (95% CI, 4.0 to 40.0) for ICH. CONCLUSIONS: This population-based study found that AIDS is strongly associated with both IS and ICH.

Acquired Immunodeficiency Syndrome↗

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↗

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↗

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.

Adult↗

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↗

Hemiparetic muscle atrophy and increased intramuscular fat in stroke patients.

OBJECTIVE: To determine if skeletal muscle atrophy and greater fat deposition within the muscle are present in the hemiparetic limb of chronic (>6 mo) hemiparetic stroke patients. DESIGN: Cross-sectional study. SETTING: Hospital-based research center. PARTICIPANTS: Sixty patients (47 men, 13 women; mean age +/- standard deviation, 65+/-9 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients underwent a total body scan by dual-energy x-ray absorptiometry to determine percentage of body fat, total lean mass, fat mass, and lean mass of the paretic and nonaffected legs, thighs, and arms. Thirty patients received computed tomography (CT) scans of their midthigh to determine muscle area, subcutaneous fat, and low-density lean tissue, as a measure of fat within the muscle area, of the paretic and nonaffected midthigh. RESULTS: Patients were deconditioned (VO(2)peak: 1.2+/-0.3 L/min) with a percentage of body fat of 31.4%+/-9.8% and total lean mass of 51.4+/-9.1 kg. Lean mass of the paretic leg and thigh were 4% and 3% lower than the nonaffected leg (P<.001), but leg fat was not different. Arm lean mass of the paretic side was 7% lower than the nonaffected side, whereas arm fat was not different. CT studies showed that midthigh muscle area was 20% lower in the paretic limb than in the nonaffected leg (P<.001), midthigh subcutaneous fat was similar, and midthigh low-density lean tissue showed a trend to be 3% higher in the paretic leg (P=.06). The ratio of midthigh low-density lean tissue to muscle area was higher in the paretic leg (P<.001), which indicates a greater intramuscular fat relative to muscle area in the affected limb. CONCLUSIONS: Our results show hemiparetic skeletal muscle atrophy and more fat within the muscle, factors that may contribute to functional disability and increased cardiovascular disease risk in chronic hemiparetic stroke patients.

Absorptiometry, Photon↗

Microprocessor-based ambulatory activity monitoring in stroke patients.

PURPOSE: Recovery of ambulatory function after stroke is routinely assessed using standardized subject- or observer-rated instruments that do not directly measure ambulatory activities in the home-community setting. Accuracy of conventional pedometers in stroke patients is not established, limiting their application in mobility outcomes monitoring. This study investigates the accuracy and reliability of a mechanical pedometer versus microprocessor-based step activity monitoring (SAM) in gait-impaired hemiparetic stroke patients. METHODS: Accuracy and test-retest reliability of ankle-worn SAM and belt-worn pedometer were tested directly against hand tallied stride counts and cadence during a battery of timed walks in 16 chronic hemiparetic stroke patients. Patients performed replicate 1-min floor walks at self-selected and fastest comfortable paces, and two 6-min walks on separate days. RESULTS: SAM cadence and total stride counts are more accurate than pedometers during 1-min walks at self-selected (99 +/- 1 vs 87 +/- 11.3%, mean +/- SD, P < 0.01); fast pace (98 +/- 2.3% vs 85 +/- 15%, P < 0.01); and repeated 6-min walks performed on separate days (99 +/- 1% vs 89 +/- 12%, P < 0.01). Although SAM is highly reliable (r = 0.97, P < 0.0001) and accurate in all patients under every walking condition tested, the mechanical pedometer demonstrates this high level of accuracy in only half of stroke patients and has poor test-retest reliability (r = 0.64, P < 0.05). CONCLUSION: SAM, but not the conventional pedometer, provides accurate and reliable measures of cadence and total stride counts in hemiparetic stroke patients. Portable microprocessor-based gait monitoring offers potential to quantitatively measure home-community-based ambulatory activity levels in this population.

Gait↗

Antiphospholipid antibodies and stroke in young women.

BACKGROUND AND PURPOSE: Antiphospholipid antibodies have been associated with ischemic stroke in some but not all studies. METHODS: We performed a population-based case-control study examining antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulants) using stored frozen sera and plasma in 160 cases and 340 controls enrolled in the Stroke Prevention in Young Women study. We evaluated for the presence of anticardiolipin antibody (IgG, IgM, and IgA isotypes) by an enzyme-linked immunosorbent assay and for the lupus anticoagulant using several phospholipid-dependent coagulation tests (activated partial thromboplastin time, dilute Russell's viper venom time) with mixing studies. If mixing studies were prolonged, confirmatory tests were performed. RESULTS: A positive anticardiolipin antibody level of any isotype was seen in 43 cases (26.9%) and 62 controls (18.2%) (P=0.03), lupus anticoagulant in 29 cases (20.9%) and 38 controls (12.8%) (P=0.03), and either anticardiolipin antibody or lupus anticoagulant in 61 cases (42.1%) and 86 controls (27.9%) (P=0.003). After adjustment for age, current cigarette smoking, hypertension, diabetes, angina, ethnicity, body mass index, and high-density lipoprotein levels, the relative odds of stroke for women with anticardiolipin antibody immunoreactivity of any isotype or a lupus anticoagulant was 1.87 (95% confidence interval, 1.24 to 2.83; P=0.0027). CONCLUSIONS: The results from this study support the importance of antiphospholipid antibodies as an independent risk factor for stroke in young women.

Adolescent↗

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↗

Increased circulating concentrations of the counteradhesive proteins SPARC and thrombospondin-1 in systemic sclerosis (scleroderma). Relationship to platelet and endothelial cell activation.

OBJECTIVE: To determine whether circulating concentrations of the counteradhesive proteins SPARC (secreted protein acidic and rich in cysteine) and thrombospondin-1 (TSP-1) are elevated in scleroderma (systemic sclerosis, SSc). The relationship of these counteradhesive proteins to measures of platelet and endothelial cell activation was examined. METHODS: Plasma from 45 patients with SSc (26 limited form, 19 diffuse) and 22 age and sex matched controls was assayed for SPARC, TSP-1, beta-thromboglobulin (betaTG), and platelet factor 4 (PF4), 2 distinct platelet a-granule products, and soluble E-selectin, a marker of endothelial cell activation. RESULTS: The mean (+/- SE) SPARC concentration was greater in patients with limited SSc (124.0 +/- 9.6 ng/ml) compared to controls (66.8 +/- 8.0 ng/ml) (p = 0.0005), whereas in patients with diffuse SSc (74.1 +/- 7.9 ng/ml) it was not. Elevated SPARC concentrations in the limited SSc group could not be ascribed to either platelet or endothelial cell activation. TSP-1 concentrations were also increased in SSc patients (n = 29) compared to controls (n = 11) (2.98 +/- 0.12 vs 2.4 +/- 0.21 log transformed ng/ml; p < 0.02). Unlike SPARC, TSP-1 concentrations correlated with both betaTG (r = 0.57, p = 0.0014) and PF4 (r = 0.41, p = 0.026) levels, indicating that increased TSP-1 could, in part, be explained through elevated platelet a-granule release in SSc patients. Plasma levels of betaTG, PF4, and E-selectin were each similarly elevated (p < 0.003) in patients with both limited and diffuse SSc compared to controls. CONCLUSION: That circulating SPARC and TSP-1 are elevated in patients with SSc raises the possibility that counteradhesive proteins, which regulate vascular organization and remodeling, might contribute to the pathogenesis of SSc vasculopathy.

Adult↗

Testing a model of post-stroke exercise behavior.

Stroke is the leading cause of disability in older Americans, and survivors tend to be sedentary, thereby risking loss of functional gains achieved during rehabilitation and increasing cardiovascular risk. Studies of motivation to exercise in older adults suggest that self-efficacy and outcome expectations are key determinants of initiation and adherence to exercise programs. This study tested a theoretical model of physical activity in stroke survivors. A survey of exercise beliefs and patterns was sent to National Stroke Association stroke support groups. Responses from 312 stroke survivors (mean age 63 years, 57% female, 70% White) indicated that only 31% exercised four times weekly. Self-efficacy and outcome expectations for exercise, before exercise history, and physician recommendation all directly and indirectly influenced self-reported exercise behavior and accounted for 33% of the total variance in exercise behavior. Model testing supported the theory and the model fit the data. Interventions to strengthen self-efficacy and outcome expectations for exercise, along with reminders for clinicians to encourage regular exercise programs, may increase the likelihood of initiating and maintaining an exercise program, potentially improving physical function and cardiovascular fitness in this population.

Analysis of Variance↗

Fatigue after stroke: relationship to mobility, fitness, ambulatory activity, social support, and falls efficacy.

Fatigue is common and persistent in stroke survivors, yet it is not known how mobility deficits, fitness, or other factors, such as social support, relate to fatigue severity, or whether subjective fatigue contributes to reduced ambulatory activity. The severity of fatigue in a sample of 53 community-dwelling subjects with chronic hemiparetic stroke was examined, and relationships among fatigue and mobility deficit severity, cardiovascular-metabolic fitness, ambulatory activity, social support, and self-efficacy for falls were identified. Measures included the Fatigue Severity Scale, timed 10-meter walks, the Berg Balance Scale, submaximal and peak VO2, total daily step activity derived from microprocessor-linked Step Activity Monitors, the Medical Outcomes Study Social Support Survey, and the Falls Efficacy Scale. Forty-six percent of the sample had severe fatigue. Fatigue showed no relationship to ambulatory activity. Fatigue severity was associated with the Berg Balance Scale (p < .01) and falls efficacy (p < .01), but not with cardiovascular fitness variables. Patients with elevated fatigue severity scores had lower social support (p < .05) and poorer falls efficacy scores (p < .05) than patients reporting less fatigue. Only falls efficacy was predictive of fatigue severity (r2 = 0.216, p < .01). Further studies are needed to evaluate whether rehabilitation strategies that include not only fitness and mobility interventions, but also social/behavioral and self-efficacy components, are associated with reduced fatigue and increased ambulation.

Accidental Falls↗