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Rehabilitation Physiology Lab


Abstracts

OSTEOARTHRITIS

Graham J, N Fisher. Effects of Resistance Training on Muscle Function in Individuals with Knee Osteoarthritis. Arthritis & Rheumatism 48(9) suppl: S445, 2003.

Purpose: Understanding the relationship between resistance exercise training and function is important for developing effective rehabilitation programs for knee osteoarthritis (OA). The purpose of the study was to examine differences in knee flexor and extensor muscle function (strength, endurance and electromyographic (EMG) activity) in individuals with OA of the knee compared to an age-matched well elderly (WE) group before and after 8 weeks of quantitative progressive resistance exercise.

Methods: A sample of convenience was recruited for this quasi-experimental pretest / posttest design. Thirty-three individuals with knee OA (12 men, 21women) and 55 without OA (27 men, 28 women) participated in this study. Mean ages were 71.6+5.8 and 71.3+2.3 yrs, respectively. Pain and difficulty performing daily activities, quadriceps and hamstrings function, and 50-foot walk time were assessed. Strength testing involved maximal voluntary isometric contractions (MVIC) using a strain gauge. Endurance was calculated from a sustained (90sec) MVIC. Activation of the rectus femoris was assessed using surface EMG. Training consisted of isometric, isotonic, endurance, and speed contractions performed 3 days per week for 8 weeks. Exercise progression was based on each participant's initial quantitative muscle function assessment. Descriptive statistics, t-tests, and analyses of variance (p<0.05) were used to analyze the data.

Results: Walking time, hamstring strength (26 and 15%) and endurance (44 and 17%), and quadriceps strength (13 and 16%) and endurance (18 and 17%) after the 8 weeks of resistance training significantly increased for the OA and WE groups, respectively. The OA group had significantly lower strength than the WE group before and after training. EMG activity for the quadriceps strength and endurance contractions was significantly higher for the OA group initially and generally did not change with training. The WE group showed a significant increase in EMG activity during strength contractions and a decrease during endurance contractions. Pain was significantly reduced after training in the OA group, while difficulty with everyday activities was reduced in the WE group.

Conclusion: Functional performance and muscle function were reduced in OA compared to WE individuals. Both groups significantly improved after 8 weeks of specific quantitative progressive resistance exercise rehabilitation. While parallel trends were observed between force and integrated EMG (iEMG) in the WE group, this pattern was not observed in the OA group. This mismatch in force:iEMG ratio requires further consideration.


MULTIPLE SCLEROSIS

Fisher NM, J Lenox, CV Granger, L Jacobs, C Brownsheidle.
Effects of an anti-fatiguing exercise program on fatigue and physiological function in patients with multiple sclerosis
. Neurology 54(7)Suppl 3:A338, 2000.

This study measured the effects of a simulated workday and overnight recovery on total, mental and physical fatigue, physiologic capacity and functional performance in patients with multiple sclerosis (MS). The efficacy and effects of an anti-fatiguing resistance exercise program on these parameters was also evaluated. MS is a common, chronic and debilitating disease with long term health consequences. The most debilitating symptom is the lingering fatigue that follows activity and limits function. Little data are available to quantify this fatigue or examine the physiological mechanism behind it. Physical activity increases fatigue and therefore exercise therapy has been overlooked as a treatment. We developed a program of resistance exercises, individually prescribed, to avoid fatigue while improving physiological capacity. This exercise program had not been tested previously in patients with MS. A pre-post-test repeated measures design was used with 16 patients (age=43+9yrs, weight=71+16kg) with confirmed MS (MRI). All subjects had EDSS scores of <6.5 and could ambulate a minimum of 50 ft. Tests were conducted in the morning, after a simulated workday, and the next morning, prior to and after the exercise program. Fatigue (total, mental, physical, force-time index), upper and lower body muscular strength, endurance, speed, and functional performance were measured in each test session. Data for each parameter were examined by Analysis of Variance for Repeated Measures (p<0.5). Subjects participated in the 16-week progressive anti-fatiguing resistance exercise program 3 days per week, 1 hour per day. All subjects completed all aspects of the study. They had increased fatigue at the end of the simulated workday (70%-108%), which remained until the next day (46%-76%). After the exercise program, the subjects were not fatigued at the end of the simulated workday or the next morning (residual). Maximal aerobic power, muscular strength, endurance, speed and functional performance were below control levels, but increased significantly after the anti-fatiguing exercise program by 16%, 42-75%, 43-97%, 192% and 8-14%, respectively. Patients with MS have reduced functional performance due to increased fatigue, which is secondary to the reductions in aerobic and muscular capacity. A simulated day's work increased fatigue and depressed physiological performance. These changes were still evident after a night's rest, suggesting a residual effect of a day's work on both fatigue and physiological variables. The patients enthusiastically completed the anti-fatiguing resistance exercises without exacerbation. The exercise program improved all physiological variables, led to reduced fatigue during the workday, eliminated the residual fatigue and improved functional performance. This anti-fatiguing resistance exercise program was beneficial to patients with MS and could serve to increase individual productivity and thus, could reduce disability and its associated costs in these patients.


JUVENILE ARTHRITIS

Venkatraman JT, NM Fisher, K Meksawan, A Krishnan, A Downie. Effects of resistance exercise training (RET) on chemokine levels in juvenile arthritis (JA) . FASEB J 14(4):A526,#367.1, 2000.

A specific RET program has a positive physiological and functional impact in children with JA. This may be due to the modulation of chemokines and cytokines, which are implicated in mediating chemotaxis and inflammation. This study evaluates the effect of a RET on the levels of chemokines in JA children. Eighteen children (ages 6-16 yrs; Control (C, n=8); JA-Control (JA-C, n=4); JA-Exercise (JA-Ex, n=6) participated in the study. Blood was collected at baseline (pre-1), after a graded cycle exercise test (GXT) (pre-2), 8 wks later (post-1), and 8 wks later after a GXT (post-2). PBMN cells were cultured with LPS and PHA and chemokines were determined by ELISA. The production of RANTES by PBMN cells was significantly different in the C and JA groups. Significant differences were also observed between JA-C and JA-Ex for MIP-1alpha, MIP-1beta and RANTES production by PBMN cells. Significant decreases (48%) in MIP-1alpha and in MIP-1beta (34%) levels in post-1 compared to pre-1 were observed. MIP-1alpha was significantly decreased (36%) in post-2 compared to pre-2. The levels of MIP-1alpha and MIP-1beta were lower in JA-Ex while RANTES was significantly higher in JA-Ex. This study suggests that chemokine levels are different in C and JA groups. The RET program can modulate the levels of specific chemokines in JA subjects and may have potential in normalizing chemotaxis, resulting in the reduction of inflammation in JA. (Funded by NIDRR #H133G70156)


Lin H, JT Venkatraman, N Fisher, K O'Neil, P Gong, W Chu. Effects of quantitative rehabilitation exercise (QPER) on biochemical indices in juvenile arthritis (JA) . FASEB J 13:A931,#687.8, 1999.

Children with JA typically experience chronic pain, joint inflammation, stiffness and deformity. Appropriately prescribed exercise rehabilitation programs may reduce inflammation. The present study evaluated the effects of 8 wks of QPER on physiologic, biochemical and immunologic function in JA children. Eighteen children (age: 6-14 yrs; Control (C)-8; JA-C: 4, JA-Ex: 6) participated in the study. Blood was collected at baseline (pre-1); after a graded exercise test (CV) (pre-2); after 8 wks (post-1) and after 8 wks+CV test (post-2). ANOVA revealed significantly lower levels of plasma lactate in JA-C Vs C (p<0.03). Plasma lactate levels significantly increased after the CV test in the C group (17+1.3mg to 32.6+3.3mg/100ml) while not in the JA group. After 8wks of QPER, lactate levels increased significantly after post-2 test (15mg to 22mg/100ml) in the JA-Ex group. Plasma hemoglobin levels were significantly lower in the JA children. Plasma glucose level (60-80mg/100ml) was similar in all the groups and was not altered by the CV test. Plasma cholesterol and triglycerides (TG) levels were significantly lower in children with JA compared to C. Preliminary data suggest that the QPER program had no adverse effects and increased the anaerobic glycolytic capacity in JA children. (Funded by National Institutes of Disability & Rehabilitation Research).




Venkatraman JT, N Fisher, K O'Neil, H Lin, W Chu. Effects of quantitative rehabilitation exercise (QPER) on the function of neutrophils (PMN) in children with juvenile arthritis (JA) . FASEB J 13:A846,#644.4, 1999.

Neutrophils have been implicated in tissue destructive events in inflammatory disease. Their function depends on their ability to adhere to microvascular endothelium and extracellular matrix components and to respond with a respiratory burst. The present study evaluated the effects of 8 wks of QPER on PMN function in JA children. A total of 18 children (ages of 6-14 yrs; Control (C): 8; JA-C: 4, JA-EX: 6) participated in this study. Blood was collected at baseline (pre-1), after a graded exercise (CV) test (pre-2), 8wks later (post-1) and 8 wks later after the CV test (post-2). PMN were separated from blood using HistopaqueR gradients. The adherence and respiratory burst of PMN was tested in the presence of formyl-methionyl-leucyl-phenylalanine (fMLP; a chemotactic peptide) and phorbol 12-myristate 13-acetate (PMA). ANOVA revealed that the adherence of PMN was significantly lower (40% lower0 in JA children. Adherence increased to normal levels after 8wks of QPER. There were significant differences in the respiratory burst of PMN between the C and JA groups. Significant differences in respiratory burst were also observed between Pre-1 & Pre-2 and Pre-2 & Post-2. Preliminary data suggest that abnormalities occur in neutrophil adherence and respiratory burst in JA children. A specific muscle exercise training program may have potential for normalizing PMN function and reducing inflammation in JA children. (Funded by NIDRR).




Fisher NM, JT Venkatraman, KM O'Neil. Effects of resistance exercise on children with juvenile arthritis . Arthritis Rheum 42(9)Suppl:S396, 1999.

Juvenile arthritis (JA) is a common chronic condition in children, leading to long term disability. This project measured the effects of exercise rehabilitation on muscular, cardiovascular and functional performance, and pain in children with JA. Six subjects (JA-EX mean age=10+2.7yrs) diagnosed with JA participated in an 8-week resistance exercise program. Pre and post-tests of maximal isometric strength and endurance of the quadriceps and hamstrings, speed of muscle contraction, submaximal and maximal oxygen consumption (VO2), heart rate (HR), blood pressure (BP), as well as pain, disability and functional performance were conducted. The individualized resistance exercise program was designed based on the pre-test results. Two control groups, normal controls (C, n=13, age=9.2+2.4 yrs) and JA controls (JA-C, n=5, age=8.8+1.8 yrs) participated in the pre and post-tests, but not the exercise program. Results were statistically analyzed using repeated measures ANOVA (p<.05). After resistance exercise, the JA-EX group had significant increases in quadriceps strength (48%), hamstring strength (99%), quadriceps endurance (32%), hamstring endurance (59%), and contraction speed (46%-69%). VO2max, maximal HR and systolic BP increased 15%, 5%, and 10%, respectively. Overall functional performance (10%) and functional status (32%) increased and pain (42-51%), disability (26%) and the number of medications used (25%) decreased significantly. The JA subjects were more compromised than C on most variables. Whereas C increased hamstring strength (17%) and endurance (25%). JA-C decreased (42-45%) from pre to post. Also, JA-C had increased pain (74%), disability (10%) and medication use (54%). This project provides evidence that a specific resistance exercise rehabilitation program has a positive physiological and functional impact, as well as the ability to reduce pain, disability and medication use, on children with JA. (Supported by the National Institute on Disability and Rehabilitation Research, #H133G70156)




Venkatraman JT, NM Fisher, HJ Lin, KM O'Neil. Effects of resistance exercise on plasma levels and production of cytokines and lipid mediators in juvenile arthritis . Arthritis Rheum 42(9)Suppl:S396, 1999.

An abnormal production of proinflammatory cytokines and lipid mediators may lead to inflammation and the progression of many autoimmune diseases. The present study evaluated the effects of 8 weeks of resistance exercise training on plasma levels and the production of cytokines and lipid mediators produced by PBMN cells in JA children. Eighteen children (ages 6-14 yrs; Control (C, n=8); JA-Control (JA-C, n=4); JA-EX, n=6) participated in the study. Blood was collected at baseline (pre-1), after a graded cycle exercise test (GXT) (pre-2), 8 wks later (post-1) and 8 wks later after GXT (post-2). PBMN cells were prepared using HistopaqueR gradients. Cells were cultured with LPS and PHA; cytokines and lipid mediators were determined by ELISA. Results were analyzed statistically using ANOVA (p<.05). PGE2, LTB4, IL-2, IFN-( and plasma TXB2 and IL-4 were significantly different between the C and JA groups. Significant differences were also observed between JA-C and JA-EX for IFN-(, IL-4 and IL-8. From pre-1 to post-1, there were significant differences between groups in PGE2, IL-4, plasma IFN-( and IL-4 levels. From pre-2 to post-2, there were changes between groups in IL-2, IFN-(, plasma IFN-( and IL-4, JA-EX was different from JA-C for IL-12 and plasma PGE2, IL-2, IFN-(, after resistance exercise. There were significant effects on the production of IL-2, IFN-( and plasma IFN-( from pre to post-GXT. Significant effects between pre-1 vs. post-1 and pre-2 vs post-2 were observed for the production of IL-2, IFN-( and plasma levels of IFN-(, IL-12 and PGE2 (pre-2 vs post-2 only) Data from the present study suggest that the levels of cytokines and lipid mediators are different between the JA and C subjects. The 8-week resistance exercise program significantly modulated these levels in JA. A specific muscle exercise rehabilitation program in JA children may have potential in correcting the imbalances in proinflammatory cytokines and lipid mediators and thereby, reduce inflammation in JA. (Supported by the National Institute on Disability and Rehabilitation Research. #H133G70156)




Velazquez V, NM Fisher, JT Venkatraman, KM O'Neil. Effect of lower extremity resistance exercise rehabilitation on interleukin-1-beta, interleukin-1RA, and interleukin-6 in juvenile arthritis . Arthritis Rheum 42(9)Suppl:S185, 1999.

Inflammation in juvenile arthritis (JA) is promoted by the cytokines, interleukin-1( (IL-1), and interleukin-6 (IL-6), and is opposed by the IL-1 receptor antagonist (IL-1RA). Exercise may affect inflammatory activity in JA by influencing production of cytokines or their antagonists. We examined the effects of an 8 week individualized resistance exercise program on plasma concentrations and cultured mononuclear cell production (24 hr sups + 100 ng/ml LPS) of IL-1, IL-6, and IL-1RA in 9 children with JA and 9 healthy controls (C). Six JA subjects exercised; 3 served as disease controls. Blood was sampled prior to and following cycle graded exercise testing (GXT), both pre- and post-exercise training. Cytokines were measured with ELISA kits (R&D). IL-1 was undetectable in 6/9 plasmas in each group. In unstimulated sups, IL-1 was detectable in 0/9 C and 4/9 JA subjects. In LPS-stimulated C sups, IL-1 increased with GXT from 2534+658 to 2807+533 pg/ml (mean+sem); JA did not differ from C before or after exercise training, and showed no consistent response to GXT. IL-6 was detected in plasma from 1/10 C and 4/9 JA subjects. In unstimulated PBMC sups from C, 189+73 pg/ml IL-6 was present at baseline, and did not change with GXT. JA sups contained 657+586 pg/ml IL-6 and did not change with GXT, but dropped significantly to 233+195 pg/ml after exercise training. Plasma IL-1RA was detected in 3/10 C subjects (all after GXT), and 5/9 JA subjects (3 pre- and 5-post GXT). Unstimulated sups from C contained 361+48 pg/ml IL-1RA at baseline; sups from JA contained 453+89 pg/ml, and neither changed with GXT. Following exercise training, IL-1RA in unstimulated JA sups fell to normal at 344+57 pg/ml. Il-1RA in LPS-stimulated C sups was 566+77 pg/ml at baseline, and 659+95 after GXT. In JA sups, IL-1RA was 651+71 pg/ml at baseline, and was 707+103 after GXT. Following exercise training, stimulated IL-1RA production decreased to 474+39 pg/ml and not change with GXT.
Resistance exercise training affects production of inflammatory mediators in JA.




Velazquez V, NM Fisher, JT Venkatraman, KM O'Neil. The effect of a lower extremity resistance exercise rehabilitation program on TNF-alpha and TNF receptors in juvenile arthritis. Arthritis Rheum 42(9)Suppl:S230, 1999.

Tumor necrosis factor-( and its soluble receptors play an important role in arthritis. TNF-( promotes, and its soluble receptors can inhibit inflammation. Exercise can improve function in arthritis, but its effect on inflammation is not defined. We studied the effects of an 8 wk. resistance exercise program in juvenile arthritis (JA) on TNF and sTNF-RI and RII in plasma and PBMC supernatants. Nineteen children, ages 6-14 yr., 10 healthy controls (C) and 9 with JA affecting lower extremities were enrolled. Six JA subjects exercised; 3 served as disease controls. Blood was drawn before and after graded cycle exercise testing (GXT) both pre- and post-exercise training. Mononuclear cells were cultured for 24 hr + 100 ng/ml LPS. TNF-alpha, sTNF-RI and sTNF-RII were measured using ELISA. Data were analyzed with one-way ANOVA. TNF was undetectable (<4.4 pg/ml) in all plasmas. In unstimulated PBMC sups, TNF was detected in 2/10 C and 5/9 JA subjects, and showed no consistent response to GXT or exercise training in any group. LPS-stimulated sups from control subjects contained 669+98 pg/ml TNF pre-GXT (mean+sem), compared to 1191+121 pg/ml in JA sups; following exercise training, JA pre-GXT TNF was normal at 664+246 pg/ml. The GXT increased LPS-induced TNF in all groups: to 801+102 pg/ml in C, 1362+237 pg/ml in JA, and 694+289 pg/ml in JA after the exercise program. sTNF-RI was detected in few sups: 2/25 C and 2/24 JA unstimulated; and 3/25 C and 1/12 JA LPS-stimulated. Plasma TNF-RI in C and JA subjects before the exercise program was similar (C=748+64 pg/ml and JA=864+45 pg/ml). After training, sTNF-RI in JA was higher at 1018+69 pg/ml pre-GXT and 988+62 pg/ml post-GXT. sTNF-RII was found in all plasmas and stimulated sups, but did not differ among groups, after GXT, or exercise training. JA subjects demonstrated a decrease in LPS-induced TNF-alpha production to normal, and an increase in plasma sTNF-RI following exercise training. Thus, the balance between TNF and sTNF-RI is shifted by the resistance exercise rehabilitation program toward anti-inflammatory conditions. (Supported by NIDRR #H133G70156)