Motor unit firing variability and synchronization during short-term light-load training in older adults.

We compared motor unit synchronization and firing rate variability within and across synergistic hand muscles during a pinching task following short-term light-load training to improve force steadiness in older adults. A total of 183 motor unit pairs before training and 158 motor unit pairs after training were recorded with intramuscular fine-wire electrodes within and across the first dorsal interosseous (FDI) and adductor pollicis (AdP) muscles during a pinch task performed by ten older adults before and after a 4-week short-term light-load training program. Nine younger adults performed the same experimental sessions 4 weeks apart with no training intervention. Two-minute sustained contractions of 2, 4, 8, and 12% maximal voluntary contraction (MVC) were performed with the non-dominant hand. The coefficient of variation (CV) of force was greater in older than in younger adults and was lower at the 2 and 4% MVC levels in both the finger (0.12 +/- 0.01 vs. 0.08 +/- 0.01, and 0.08 +/- 0.01 vs. 0.05 +/- 0.01, respectively) and thumb (0.11 +/- 0.01 vs. 0.08 +/- 0.01, and 0.09 +/- 0.01 vs. 0.05 +/- 0.01, respectively) compared to higher force levels following training in the older adults. There were no changes in CIS or k'-1 values following training. Motor unit firing rate variability significantly decreased at low force levels in the FDI muscle and also tended to decrease with training in the AdP muscle (p = 0.06). No changes occurred in the younger control group. These findings are the first to show that motor unit synchronization does not change during light-load training. Thus, it is likely that force steadiness in older adults improves by reducing motor unit firing variability rather than by changing motor unit synchronization.

Physical functioning in patients with chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) treated with dialysis have reduced levels of physical functioning. Little is known of the physical functioning in patients prior to initiation of renal replacement therapy (RRT). The purpose of the study was 2-fold: (i) to document physical functioning of patients with CKD not requiring RRT, using objective laboratory tests, physical performance measures and self-reported functioning; and (ii) to determine the correlations between these measures of physical functioning and renal function. METHODS: Thirty-two patients with CKD (mean estimated glomerular filtration rate [eGFR] 29.9 +/- 17.0) were recruited for the study. Subjects completed symptom-limited treadmill test (peak oxygen uptake [VO2peak]), physical performance measures (gait speed, sit-to-stand and 6-minute walk) and the SF-36 Health Status Questionnaire (physical functioning scale [PF] and physical composite scale [PCS]). Descriptive and correlational analyses were performed on the data. RESULTS: VO2peak (O2 17.8 +/- 6.7 ml/kg body weight per minute), physical performance measures and self-reported functioning were reduced compared with sedentary age-predicted norms. Significant correlations were found between VO2peak and all other physical functioning measures; however, only maximal gait speed and PCS correlated significantly with eGFR. CONCLUSIONS: Patients with CKD have reduced physical functioning as measured using objective laboratory tests (VO2peak), physical performance measures and self-reported functioning. Given that low physical functioning predicts outcomes in dialysis patients, interventions to maintain or improve physical functioning are warranted prior to initiation of dialysis.

A randomized trial of exercise and dietary counseling after liver transplantation.

We report results of a randomized clinical trial of a combined intervention of exercise and dietary counseling (ExD) after orthotopic liver transplantation (OLT). Of the 151 patients randomized into ExD or usual care (UC), 119 completed testing 2, 6 and 12 months post-OLT. Testing included assessment of exercise capacity (VO(2peak)), quadricep muscle strength, body composition (DXA), nutritional intake (Block 95) and health-related quality of life (SF-36). The intervention consisted of individualized counseling and follow-up to home-based exercise and dietary modification. Repeated measure ANOVA was performed to determine differences over time between ExD and UC with a secondary analysis to determine differences over time between adherers (Adh), nonadherers (Nadh) to the intervention and UC. The ExD group showed greater increases in VO(2peak) (p = 0.036), and self-reported general health (p = 0.038) compared to UC. Both groups demonstrated increases in muscle strength, body weight, body fat and other SF-36 scale scores. Adherence to the intervention was 37% with positive trends in VO(2peak) and body composition observed in Adh compared to Nadh and UC. These data suggest improvements in exercise capacity and body composition are achieved with nutrition and exercise behavior modifications initiated early after OLT and with regular follow-up.

Alterations in skeletal muscle structure are minimized with steroid withdrawal after renal transplantation.

BACKGROUND: Limitations in exercise capacity in kidney transplant recipients are thought to result in part from changes in muscle structure and function associated with immunosuppression therapy. METHODS: We compared the percent distribution of skeletal muscle fiber types, cross-sectional areas, and ultrastructural morphologies in kidney transplant recipients treated with standard prednisone maintenance therapy (n=21) to those undergoing rapid withdrawal of prednisone using Simulect (interleukin 2 receptor inhibitor) (n=13). Skeletal muscle biopsy specimens from the vastus lateralis were analyzed at 3 and 12 months after transplantation and compared with sedentary controls (n=15). RESULTS: Compared with the control group, the group receiving prednisone maintenance therapy had a significantly lower percentage of type I fibers and a higher percentage of type IIB/x fibers, evident at 3 and 12 months. Fiber type distribution in patients withdrawn from prednisone did not differ from controls. In patients withdrawn from prednisone, the cross-sectional areas of type I and IIA fibers were lower and the area of type IIB/x fibers was higher compared with controls. Likewise, ultrastructural studies revealed reduced volume densities of myofibrils and higher densities of interfibrillar and subsarcolemmal mitochondria. At 12 months there were no ultrastructural differences between the patients withdrawn from prednisone and controls. CONCLUSIONS: We conclude that prednisone maintenance therapy contributes to the lower exercise capacity by altering the ratio of type I to type IIB/x fibers and by reducing myofilament density. The increase in mitochondria in patients receiving prednisone may reflect a switch from carbohydrate to lipid metabolism resulting from the glucocorticoid therapy.

Determinants of physical performance in ambulatory patients on hemodialysis.

BACKGROUND: Physical performance measures, particularly gait speed, have been useful as predictors of loss of independence, institutionalization, and mortality in older nonuremic individuals. Gait speed has not been evaluated as a predictor of these important outcomes in patients on hemodialysis, nor have the determinants of gait speed in the dialysis population been studied. METHODS: We performed a cross-sectional analysis to determine whether demographic, clinical, or nutritional status variables were related to physical performance in a group of 46 hemodialysis patients treated at three University of California San Francisco-affiliated dialysis units. Three physical performance measures were examined, including gait speed, time to climb stairs, and time to rise from a chair five times in succession. Forward stepwise linear-regression analysis was performed with each physical performance measure as the dependent variable and the following candidate predictor variables: age, gender, body mass index, dialysis vintage, Kt/V, albumin, blood urea nitrogen, creatinine, hematocrit, lean body mass, phase angle, ferritin, and the following comorbidities: hypertension, diabetes mellitus, coronary artery disease, peripheral vascular disease, and cerebrovascular disease. RESULTS: Subjects included 31 men and 15 women aged 22 to 87 years (mean +/- SD, 52 +/- 17). The mean gait speed for the group was 113.1 +/- 34.5 cm/s (low compared with norms established for persons of similar age). Results of multivariable regression showed that age, albumin, and Kt/V were important determinants of gait speed in this population. Overall, the model explained 52% of the variability in gait speed (r = 0.72, P < 0.0001). Qualitatively similar results were obtained using stair-climbing time or chair-rising time as the dependent variables, except that comorbidity was more important than age for stair climbing. The addition of physical activity level to the models did not eliminate the associations of albumin or Kt/V with physical performance. CONCLUSIONS: Physical performance is significantly impaired in ambulatory hemodialysis patients and is related to age, serum albumin, and dialysis dose. Prospective studies are needed to determine whether modification of dialysis dose or nutritional interventions can improve physical performance in patients on hemodialysis.

Validation of questionnaires to estimate physical activity and functioning in end-stage renal disease.

BACKGROUND: Patients on dialysis are less physically active than sedentary persons with normal kidney function. To assess the consequences of inactivity and the results of efforts to increase activity in the end-stage renal disease (ESRD) population, valid instruments to measure physical activity and physical functioning in this group are needed. METHODS: We performed a cross-sectional study to establish the validity in ESRD of several questionnaires designed to measure physical activity or physical functioning in the general population. Questionnaires studied included the Stanford 7-day Physical Activity Recall questionnaire (PAR), the Physical Activity Scale for the Elderly (PASE), the Human Activity Profile (HAP), and the Medical Outcomes Study Short Form 36-item questionnaire (SF-36). Physical activity was measured using three-dimensional activity monitors (accelerometers) over a seven-day period (the "gold standard"). Patients also underwent physical performance tests, including measurement of gait speed, stair climbing time, and chair rising time. Study questionnaires were administered, and questionnaire results were compared with each other and with activity monitor and physical performance test results. RESULTS: Thirty-nine maintenance hemodialysis patients participated in the study. Dialysis patients scored worse than previously published healthy norms on all tests. All questionnaires correlated with seven-day accelerometry and with at least one measure of physical performance. The HAP correlated best with accelerometry (r = 0.78, P < 0.0001). Seventy-five percent of the variability in physical activity measured by accelerometry could be explained by a model that combined information from the HAP and the PASE. The HAP and the physical functioning scale of the SF-36 were about equally well correlated with physical performance measures. CONCLUSIONS: These questionnaires are valid in patients on hemodialysis and should be used to study the physical activity and rehabilitation efforts in this population further.

Characteristics of an Albumin Cobalt Binding Test for assessment of acute coronary syndrome patients: a multicenter study.

BACKGROUND: The ability of the N-terminal region of human albumin to bind cobalt is diminished by myocardial ischemia. The characteristics of an assay based on albumin cobalt binding were assessed in suspected acute coronary syndrome patients and in a control reference population. The ability of the Albumin Cobalt Binding (ACB) Test measurement at presentation to predict troponin-positive or -negative results 6-24 h later was also examined. METHODS: We enrolled 256 acute coronary syndrome patients at four medical centers. Blood specimens were collected at presentation and then 6-24 h later. The dichotomous decision limit and performance characteristics of the ACB Test for predicting troponin-positive or -negative status 6 h-24 h later were determined using ROC curve analysis. Results for 32 patients could not be used because the time of onset of ischemia appeared to have been >3 h before presentation or was uncertain. The reference interval was determined by parametric analysis to estimate the upper 95th percentile of a reference population (n = 109) of ostensibly healthy individuals. RESULTS: Increased cTnI was found in 35 of 224 patients. The ROC curve area for the ACB Test was 0.78 [95% confidence interval (CI), 0.70-0.86]. At the optimum decision point of 75 units/mL, the sensitivity and specificity of the ACB Test were 83% (95% CI, 66-93%) and 69% (95% CI, 62-76%). The negative predictive value was 96% (95% CI, 91-98%), and the positive predictive value was 33% (95% CI, 24-44%). The within-run CV of the ACB Test was 7.3%. Results for the reference population were normally distributed; the one-sided parametric 95th percentile was 80.2 units/mL. CONCLUSIONS: This exploratory study suggests that the ACB Test has high negative predictive value and sensitivity in the presentation sample for predicting troponin-negative or -positive results 6-24 h later.

Fitness testing of pediatric liver transplant recipients.

Liver transplantation is accepted as the standard management for end-stage liver disease in children. Pediatric heart and heart-lung transplant recipients have shown significantly diminished exercise capacities compared with age-matched, able-bodied, control subjects. The primary aim of this study is to compare the fitness levels of a group of pediatric liver transplant (LT) recipients (LT group, 20 boys, 9 girls; age, 8.9 +/- 4.8 years; 56 +/- 35 months posttransplantation) with a group of able-bodied control subjects (22 boys, 12 girls; age, 8.4 +/- 3.8 years). The secondary aim is to compare the performance of the LT group against the Fitnessgram criterion standards. We assessed muscular endurance by means of a partial curl-up, flexibility by means of the back-saver sit and reach, and cardiorespiratory fitness by means of the progressive aerobic cardiovascular endurance run (PACER). The only significant (P <.05) difference between the 2 groups was the number of shuttles run in the PACER (control, 16.8 +/- 9.8 v LT, 11.5 +/- 8.4 shuttles). Other differences between the 2 groups were not significant. With regard to satisfying the Fitnessgram criterion standards, only 35% of the LT group achieved the standards for the partial curl-up, 88% of the LT group achieved the criterion standards for flexibility, and 0% achieved the standards for the PACER. These results indicate that the LT group has diminished exercise capacity. The origins of exercise limitations deserve further investigation.

Physical activity and health-related quality of life in liver transplant recipients.

The US Surgeon General's Report on Physical Activity and Health recommends that people of all ages engage in regular physical activity, and that significant health benefits can be obtained through a moderate amount of physical activity. Physical activity appears to improve health-related quality of life (HRQOL) by enhancing physical functioning in persons compromised by poor health. The Medical Outcomes Study Short Form-36 (SF-36) Health Status Questionnaire was sent to all patients who were 5 years or more post-liver transplantation at the University of California at San Francisco. Additional questions related to coexisting medical conditions and participation in regular physical activity were included. SF-36 scale scores were compared between active and inactive patients. Regression analysis was also performed to determine the contributions of coexisting medical conditions and physical activity to the physical scales of the SF-36 questionnaire. Patients who participated in regular physical activity had significantly higher scores on all physical scales and the physical component scale (PCS). The regression model, which included age, sex, time posttransplantation, retransplantation, recurrence of hepatitis C, number of comorbid conditions, and physical activity participation showed that both the number of comorbid conditions and participation in physical activity were significant independent contributors to the physical functioning scale and PCS. This study indicates that physical activity is related to HRQOL after liver transplantation independent of other coexisting medical conditions.

Analysis of the Albumin Cobalt Binding (ACB) test as an adjunct to cardiac troponin I for the early detection of acute myocardial infarction.

Human albumin has the ability to bind cobalt at the N-terminus. The exposure of circulating albumin to ischemic tissue alters the ability of albumin to bind cobalt, probably through a mechanism involving free-radical production. The Albumin Cobalt Binding (ACB) test measures the alteration in albumin metal binding, and elevation of the ACB test is thought to be an early indicator of myocardial ischemia. In a previous multicenter study of chest pain patients presenting to the emergency department (ED), this test demonstrated high negative predictive value and sensitivity in the sample collected at presentation for predicting cardiac troponin I (cTnI)-negative or cTnI-positive results 6-24 h later. Since the completion of that report, the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) have redefined the criteria for the diagnosis of acute myocardial infarction (AMI). The data from the multicenter ACB study were re-examined using the new diagnostic criteria for AMI to determine if combining the ACB test with troponin improved the sensitivity of either assay used alone for early diagnosis of AMI. Assay values were compared to either the final discharge diagnosis made at each site or to a diagnosis of AMI using the strict application of the ESC/ACC guidelines. Using the criterion of physician's discharge diagnosis and using blood collected at ED presentation, the cTnI test alone had a sensitivity of 23.9%, and the ACB test alone had a sensitivity of 39.1%, but the sensitivity significantly increased to 55.9% (p < 0.001 over cTnI alone) when both tests were used in combination. The sensitivity of the combination of ACB and cTnI tests at the 1- to 6-h time-point was 86.7% and at the >6- to 12-h time-point was 93.5%, but they were not significantly improved over the cTnI test alone. In conclusion, using the new ESC/ACC criteria, the combination also resulted in a statistically significant higher diagnostic sensitivity on blood collected at presentation. These data indicate a possible role of the ACB test in the early triage of patients with chest pain.

Physical activity for the chronically ill and disabled.

Exercise prescription principles for persons without chronic disease and/or disability are based on well developed scientific information. While there are varied objectives for being physically active, including enhancing physical fitness, promoting health by reducing the risk for chronic disease and ensuring safety during exercise participation, the essence of the exercise prescription is based on individual interests, health needs and clinical status, and therefore the aforementioned goals do not always carry equal weight. In the same manner, the principles of exercise prescription for persons with chronic disease and/or disability should place more emphasis on the patient's clinical status and, as a result, the exercise mode, intensity, frequency and duration are usually modified according to their clinical condition. Presently, these exercise prescription principles have been scientifically defined for clients with coronary heart disease. However, other diseases and/or disabilities have been studied less (e.g. renal failure, cancer, chronic fatigue syndrome, cerebral palsy). This article reviews these issues with specific reference to persons with chronic diseases and disabilities.

Low-functioning hemodialysis patients improve with exercise training.

The Renal Exercise Demonstration Project provided two different approaches to exercise programming to a group of hemodialysis patients. Physical functioning and self-reported health-related quality of life were measured at baseline, after 2 months of independent exercise, and again after 2 months of in-center cycling. This study compares the responses to intervention of patients who initially scored low (<34) on the Physical Component Scale (PCS) on the Medical Outcomes Study Short-Form 36 questionnaire to those who initially scored higher (>34) on the same scale. The high-PCS group scored higher on all physical function tests (normal gait speed, fast gait speed, and sit-to-stand test) at each testing time than the low-PCS group. The high-PCS group improved only on the sit-to-stand test, whereas the low-PCS group improved in all three physical function tests. There were significant differences between the groups in change over time in all the physical scales and the PCS over time, with the low-PCS group showing improvements in response to the intervention and the high-PCS group showing no change over time. No differences in change over time were noted between the groups on the mental scales in either group. We conclude that low-functioning hemodialysis patients can benefit from exercise counseling in both objective measures of physical functioning and self-reported physical functioning. The impact of such interventions seems to be more profound in the lowest functioning patients.

Physical functioning and health-related quality-of-life changes with exercise training in hemodialysis patients.

The Renal Exercise Demonstration Project was designed to test the effects of two different approaches to exercise programming on the levels of physical activity, physical functioning, and self-reported health status in hemodialysis patients. Two hundred eighty-six patients were recruited for participation. Intervention patients were given individually prescribed exercise for 8 weeks of independent home exercise, followed by 8 weeks of incenter cycling during dialysis. Physical performance testing was performed at baseline and after each intervention using gait speed, sit-to-stand test, and 6-minute walk. The Medical Outcomes Study Short Form 36-item (SF-36) questionnaire was used to assess self-reported health status. The intervention group showed increased participation in physical activity. There were significant differences between the intervention and nonintervention groups in change over time in normal and fast gait speed, sit-to-stand test scores, and the physical scales on the SF-36, including the physical component scale. The intervention group improved in these test results, whereas the nonintervention group either did not change or declined over the duration of the study. It is clear that improvements in physical functioning result from exercise counseling and encouragement in hemodialysis patients. Because self-reported physical functioning is highly predictive of outcomes in hemodialysis patients, more attention to patients' levels of physical activity is warranted.

Physical functioning: definitions, measurement, and expectations.

The nephrology community has begun to recognize the importance of physical functioning in the overall treatment of their patients. Physical functioning is highly associated with such outcomes as hospitalization, nursing home admission, falling, level of dependency, and death in older individuals. Because there are many terms used to refer to physical functioning, this report classifies physical functioning into basic actions and complex activities; activities considered essential for maintaining independence, and those considered discretionary that are not required for independent living, but may have an impact on quality of life. We also present a model of the determinants of physical functioning, which goes beyond the presence or absence of disease and considers physical, sensory, environmental, and behavioral factors. Measurement of physical functioning can be complicated and ranges from self-report questionnaires to performance measures of specific tasks to vigorous laboratory measures. There are limitations to each of the measurement methods; however, some level of assessment provides information about the patient that is not otherwise available. Valid and reliable tests of physical performance are available that are easily administered and provide valuable information about the patient. Just as the patient's nutrition, medications, and adequacy of dialysis are monitored, baseline and subsequent physical functioning assessments allow us to monitor the patient's clinical course as it relates to their physical ability. Such measurement also allows for the identification of patients with lower functioning who would benefit from physical therapy or other exercise intervention.

The physiological consequences of bed rest and inactivity.

Most dialysis patients experience prolonged periods of physical inactivity and often bedrest. The physiological consequences of bed rest and inactivity are many and detrimentally affect the functioning of many bodily systems, several of which affect physical functioning. Reductions in plasma volume reduce cardiac filling, stroke volume, and cardiac output. Skeletal muscle fiber size, diameter, and capillarity are reduced, as is bone density. These changes result in profound reductions in physical work capacity. The effects of bed rest and inactivity in patients with chronic renal failure may have more serious consequences, in that they may exacerbate the pathophysiology of renal failure such as cardiac dysfunction, anemia, muscle wasting, muscle weakness, neuropathy, glucose intolerance, and reduced bone density.

Exercise after renal transplantation.

Renal transplant recipients experience troublesome side effects of the immunosuppression medication, many of which may be attenuated or ameliorated with regular physical activity. Preliminary data show that exercise training after transplantation increases exercise capacity and muscle strength and may contribute to higher quality of life after transplantation.

Multicenter clinical and analytical evaluation of the AxSYM troponin-I immunoassay to assist in the diagnosis of myocardial infarction.

We evaluated the AxSYM troponin I (cTnI) immunoassay for assisting in the detection of acute myocardial infarction (AMI). At four sites, the total imprecision (CV) over 20 days was 6.3-10.2%. The minimum detectable concentration was 0.14 +/- 0.05 microgram/L. Comparison of cTnI measurements between the AxSYM and Stratus (n = 406) over the dynamic range of the AxSYM assay demonstrated good correlation, r = 0.881, with a proportional bias: AxSYM cTnI = 3.50(Stratus cTnI) - 1. 10. The confidence intervals (95%) for the slope and intercept were 3.39-3.64 and -1.32 to -0.95, respectively. The expected cTnI concentration in healthy individuals was /=96%, in skeletal muscle injury, chronic renal disease, and same-day noncardiac surgery patients.