Muscle fiber size increases following resistance training in multiple sclerosis.

OBJECTIVE: To test the hypothesis that lower body progressive resistance training (PRT) leads to an increase of the muscle fiber cross-sectional area (CSA) and a shift in the proportion of fiber types in patients with multiple sclerosis (MS). METHODS: The present study was a two-arm, randomized controlled trial (RCT). Thirty-eight MS patients (Expanded Disability Status Scale (EDSS) 3-5.5) were randomized to a PRT group (Exercise, n = 19) or a control group (Control, n = 19). The Exercise group performed a biweekly 12-week lower body PRT program [five exercises progressing from 15RM (Repetition Maximum) towards 8RM], whereas the Control group maintained their usual daily activity level during the trial period. Muscle biopsies from vastus lateralis were taken before (pre) and after the trial (post). Thigh volume (TV) was estimated from anthropometric measurements. Isokinetic muscle strength of the knee extensors (KE) and flexors (KF) were evaluated at slow (90(°)/s) and fast (180(°)/s) angular velocities. RESULTS: In the Exercise group the mean CSA of all muscle fibers (7.9 ± 15.4% vs. -3.5 ± 9.0%, p = 0.03) and of type II muscle fibers (14.0 ± 19.4% vs. -2.6 ± 15.5%, p = 0.02) increased in comparison with the Control group. No changes occurred in the proportion of fiber types in the Exercise group. Neither was there any change in total TV. Isokinetic strength at KE180, KF90 and KF180 improved significantly after PRT when compared with the control group (10.2-21.3%, p ≤ 0.02). CONCLUSIONS: We conclude that progressive resistance training induces a compensatory increase of muscle fiber size in patients with the central nervous system disorder, multiple sclerosis.

Fatigue, mood and quality of life improve in MS patients after progressive resistance training.

Fatigue occurs in the majority of multiple sclerosis patients and therapeutic possibilities are few. Fatigue, mood and quality of life were studied in patients with multiple sclerosis following progressive resistance training leading to improvement of muscular strength and functional capacity. Fatigue (Fatigue Severity Scale, FSS), mood (Major Depression Inventory, MDI) and quality of life (physical and mental component scores, PCS and MCS, of SF36) were scored at start, end and follow-up of a randomized controlled clinical trial of 12 weeks of progressive resistance training in moderately disabled (Expanded Disability Status Scale, EDSS: 3-5.5) multiple sclerosis patients including a Control group (n = 15) and an Exercise group (n = 16). Fatigue (FSS > 4) was present in all patients. Scores of FSS, MDI, PCS-SF36 and MCS-SF36 were comparable at start of study in the two groups. Fatigue improved during exercise by -0.6 (95% confidence interval (CI) -1.4 to 0.4) a.u. vs. 0.1 (95% CI -0.4 to 0.6) a.u. in controls (p = 0.04), mood improved by -2.4 (95% CI -4.1 to 0.7) a.u. vs. 1.1 (-1.2 to 3.4) a.u. in controls (p = 0.01) and quality of life (PCS-SF36) improved by 3.5 (95% CI 1.4-5.7) a.u. vs. -1.0 (95% CI -3.4-1.4) a.u. in controls (p = 0.01). The beneficial effect of progressive resistance training on all scores was maintained at follow-up after further 12 weeks. Fatigue, mood and quality of life all improved following progressive resistance training, the beneficial effect being maintained for at least 12 weeks after end of intervention.

ELISA for the core protein of the cartilage large aggregating proteoglycan, aggrecan: comparison with the concentrations of immunogenic keratan sulphate in synovial fluid, serum and urine.

Immunological assays for fragments of the cartilage large aggregating proteoglycan, aggrecan, have been widely used to monitor cartilage turnover. These assays have commonly employed the monoclonal keratan sulphate antibody, 5D4. Keratan sulphate, however, is present in many tissues and 5D4 affinity is critically dependent on antigen structure. We have therefore raised and characterized a monoclonal antibody (1-F21) that reacts with the core protein of aggrecan without interference from the glycosaminoglycan side chains and, using this antibody, we have optimized a sensitive, competitive ELISA. The within-assay and between-assay coefficients of variation were 4.9-8.9% and 11.1-13.0%, respectively. The mean concentrations of core protein in synovial fluid, serum and urine were 76.4 micrograms/ml, 104.0 ng/ml and 81.0 ng/ml, respectively. In synovial fluids the concentrations were closely correlated with the concentrations of keratan sulphate as determined by 5D4 (r = 0.94), whereas in serum and urine there was no obvious correlation between the determinations. These findings show that measurement of both core protein and keratan sulphate results in a more precise description of aggrecan turnover.

Physical Exercise and MS Recommendations.

The use of physical exercise programmes in the rehabilitation of patients with multiple sclerosis (MS) has been a controversial issue for many years. During the last decade, however, evidence from a number of studies has suggested that exercise is a safe and efficient way to induce improvements in a number of physiological functions, which ultimately can lead to functional improvements that have a positive effect on a patients daily life. The purpose of this review is, based on the existing research, to provide clinicians with some easily administrable recommendations for the application of exercise in the rehabilitation strategy of MS.

Resistance training improves muscle strength and functional capacity in multiple sclerosis.

OBJECTIVE: To test the hypothesis that lower extremity progressive resistance training (PRT) can improve muscle strength and functional capacity in patients with multiple sclerosis (MS) and to evaluate whether the improvements are maintained after the trial. METHODS: The present study was a 2-arm, 12-week, randomized controlled trial including a poststudy follow-up period of 12 weeks. Thirty-eight moderately impaired patients with MS were randomized to a PRT exercise group (n = 19) or a control group (n = 19). The exercise group completed a biweekly 12-week lower extremity PRT program and was afterward encouraged to continue training. After the trial, the control group completed the PRT intervention. Both groups were tested before and after 12 weeks of the trial and at 24 weeks (follow-up), where isometric muscle strength of the knee extensors (KE MVC) and functional capacity (FS; combined score of 4 tests) were evaluated. RESULTS: KE MVC and FS improved after 12 weeks of PRT in the exercise group (KE MVC: 15.7% [95% confidence interval 4.3-27.0], FS: 21.5% [95% confidence interval 17.0-26.1]; p < 0.05), and the improvements were better than in the control group (p < 0.05). The improvements of KE and FS in the exercise group persisted at follow-up after 24 weeks. Also, the exercise effects were reproduced in the control group during the 12-week posttrial PRT period. CONCLUSIONS: Twelve weeks of intense progressive resistance training of the lower extremities leads to improvements of muscle strength and functional capacity in patients with multiple sclerosis, the effects persisting after 12 weeks of self-guided physical activity. LEVEL OF EVIDENCE: The present study provides level III evidence supporting the hypothesis that lower extremity progressive resistance training can improve muscle strength and functional capacity in patients with multiple sclerosis.

Multiple sclerosis and physical exercise: recommendations for the application of resistance-, endurance- and combined training.

This review summarizes the existing knowledge regarding the effects of physical exercise in patients suffering from multiple sclerosis (MS). Furthermore, recommendations are given regarding exercise prescription for MS patients and for future study directions. Previously, MS patients were advised not to participate in physical exercise. During recent years, it has been increasingly acknowledged that exercise benefits MS patients. The requirement for exercise in MS patients is emphasized by their physiological profile, which probably reflects both the effects of the disease per se and the reversible effects of an inactive lifestyle. To date the effects of exercise have only been studied in moderately impaired MS patients with an EDSS score of less than 7. Evidence exists for recommending participation in endurance training at low to moderate intensity, as the existing literature demonstrates that MS patients can both tolerate and benefit from this training modality. Also, resistance training of moderate intensity seems to be well tolerated and to have beneficial effects on MS patients, but the methodological quality of the existing evidence is in general low and the number of studies is limited. Only two studies have evaluated the effects of combined resistance- and endurance training, making solid conclusions regarding this training modality impossible.

Variations in single fibre areas and fibre composition in needle biopsies from the human quadriceps muscle.

Cross-sectional area of a single fibres and the fibre distribution were measured for the two main types of fibres in needle biopsies from the quadriceps muscle of ten healthy young males. Methodological errors expressed as coefficient of variation (CV) of a single value for the area measurements were analysed and found to be 2.4% including the intraindividual error in handling the planimeter. An inhomogeneity in distribution and size of the fibres within the quadriceps muscle was indicated by a CV within the same section of 6-8% and between repeated biopsies of 15-20%.

Microphotometric determination of glycogen in single fibres of human quadriceps muscle.

A technique for the quantitation of glycogen in single fibres of human skeletal muscle is described. By using microphotometry the loss of glycogen from cryostat sections during a PAS-staining procedure was shown to be negligible. Further, it was found that nearly all the PAS-positive material (98.5%) inside a muscle fibre is glycogen. A significantly higher mean glycogen concentration (P less than 0.001) was found in type II fibres than in type I fibres in the resting quadriceps muscle of sedentary young males. The coefficient of variation for the glycogen concentration within each fibre type was found to be 17% and 15% for type I and type II respectively. The specificity of the PAS-staining technique for glycogen was confirmed by a statistically significant correlation (r = 0.78, P less than 0.001) between the glycogen concentration measured biochemically and that calculated from microphotometry and area and thickness measurements. With the technique described, it seems possible to measure the glycogen concentration of single muscle fibres in serial sections and to calculate this in standard biochemical terms.

Computerized tomographic determination of human thigh components. The effects of immobilization in plaster and subsequent physical training.

Thigh components were estimated by computerized tomography (CT) as well as by anthropometry in two healthy male soccer players (23--29 years), who for 5 weeks had one knee immobilized in a plaster of Paris. The investigations were performed on both thighs just after removal of the cast and after 5 weeks physical training of the inactivated quadriceps muscle. The different components were easily identified on a transverse scan through the middle of the thigh. The quadriceps muscle was 26% smaller after removal of the cast in the inactivated leg as compared with the contralateral leg; no differences were observed in the remaining thigh components. After rehabilitation a specific increase (22%) in the hypotrofic quadriceps muscle was observed, whereas no changes were disclosed in the remaining thigh components. The quadriceps muscle averaged 52% of the lean component in the uninjured thigh, and the subcutaneous part of the total cross-sectional area averaged 15%. The changes in the anthropometrically determined thigh components paralleled those observed by the CT scanning procedure. It is concluded that the loss in the lean thigh volume during immobilization in plaster cast is exclusively due to waste of the quadriceps muscle. CT scanning comprises a new valid tool to study changes in thigh components.

Force-velocity relationships in the human quadriceps muscles.

Isokinetic contraction were performed with the knee extensor muscles in 15 young male soccer players. The measurements were obtained by a modified isokinetic device (Orthotron). In the range of motion the angular velocity was constant from 90 degrees to 20 degrees of knee flexion. The angular velocity could be varied from 30 to 360 degrees/s. The overall variation of the pre-set speed and the peak torque, as estimated from duplicate trials through the whole velocity range, averaged 4% and 5%, respectively. The peak torque decreased linearly with increasing angular velocity in a semilogarithmic scale. An estimate of the peak torque-velocity relationship in an experimental subject was obtained from the slope and the fibre composition in the lateral portion of the quandriceps muscle in this group of subjects especially trained in fast movements. It was concluded that the present applied isokinetic device gives the opportunities to measure force-velocity characteristics in the intact quadriceps muscle of man.

Thickness measurements of skeletal muscle sections using the light microscope.

A new device is described for improving the accuracy of measuring the thickness of cryostat sections by the focusing technique in the light microscope. The necessity of such measurements is demonstrated by the great variation (range 2.55 micrometer--11.93 micrometer) in the thickness of serial cross-sections of frozen muscle biopsies from 12 healthy men. The final dehydration of the sections was found to reduce the thickenss of fresh sections by 47%. However, dehydration caused the cross-sectional area to be reduced by only 2.8%.

Lean and fat component of the human thigh. The effects of immobilization in plaster and subsequent physical training.

Changes in thigh components were investigated with the one-legged inactivity- and training-model using 22 young healthy male soccer players, who for 4-5 weeks had one leg immobilized in a cast. They were investigated before and after the cast period and after 4 weeks' physical training of the inactivated leg. Immobilization induced a significant increase in the subcutaneous thickness and a significant decrease in the circumference of the thigh (p less than 0.01). The calculated lean thigh volume was reduced from 4.93 1 to 4.10 1 (p less than 0.01), whereas the calculated fat thigh volume (1.5 1) was unchanged. The changes reversed after four weeks of progressive dynamic training, but did not reach the pre-immobilized values. Body weight decreased from 73.4 kg to 70.8 kg (p less than 0.01) during the immobilization period and was regained after the training period. The fat fraction of the body was unchanged. It is concluded that the loss in total thigh volume during inactivation in a cast is due to waste of the muscle tissue, and further that this loss is partly concealed by an unchanged fat thigh volume.

Cigarette smoking and maximal oxygen consumption rate in humans.

The relationship of maximal oxygen uptake with tobacco consumption was investigated in sixty-one young males. There was a significant negative correlation between daily consumption of tobacco and measured maximal oxygen uptake (Vo2max) expressed relative to body weight (r = -0.368, P less than 0.01) and to lean body mass (r = -0.497, P less than 0.001), respectively. No correlation could be demonstrated with regard to predicted maximal oxygen uptake (Vo3maxp). No difference was demonstrated between Vo2maxp and Vo2max in nonsmokers and heavy smokers, whereas Vo2maxp was significantly higher (P less than 0.01) in the group of moderate smokers than Vo2max. It is concluded that tobacco smoking decreases Vo2max even in young moderate smokers. Smoking habits should be considered among factors affecting Vo2maxp from cardiac frequency at submaximal levels.

Seasonal variation of maximal oxygen consumption rate in humans.

The relationship of maximal oxygen uptake (VO2 max) and resting oxygen uptake in two seasons of the year (winter/summer) was investigated in 119 young males. The subjects were conscripts, who were investigated at the calling-up time (winter: n = 58). The two groups were comparable with respect to their anthropometric data and smoking habits, as well as their occupational and leisure time activities. VO2 max was significantly (p less than 0.01) higher in the subjects investigated in the summer time (3.35 1/min) compared with those in the winter time (3.12 1/min). There was no difference in resting VO2 expressed relatively to body weight, whereas the resting VO2 was significantly (p less than 0.05) higher in winter than in summer, when it was expressed relatively to lean body mass and body surface area. The results suggest that seasonal variation in maximal aerobic power may occur in young males; this may in turn affect their response to physical training.

Progressive resistance exercise training of the hypotrophic quadriceps muscle in man. The effects on morphology, size and function as well as the influence of duration of effort.

The effects of progressive resistance exercise (PRE) training for 4 weeks on the hypotrophic quadriceps muscle were investigated in 23 young healthy male soccer players, who had been immobilized in a plaster cast 4-6 weeks after knee ligament injuries. The subjects were allocated to two training regimes where the injured leg was trained for periods of varying duration, whereas the intensity and frequency of exercise were alike in the two groups. However no significant differences were detected between the two training groups. In the whole material the lean thigh volume of the injured leg increased from 4.09 to 4.47 litres (p less than 0.001), whereas the fat component of the thigh was unchanged. The dynamic strength (1 RM) of the injured leg increased from 14.0 kg to 27.0 kg and amounted to 87% of the control leg after 4 weeks of training. At this time the maximum isometric strength amounted to 114 Nm, which was 63% of strength in the control leg. Succinate dehydrogenase (SDH) in homogenates of muscle biopsy sample increased (i.e. 20%, p less than 0.05) to the same level as found in the control leg. No changes in phosphofructokinase (PFK) were observed. The type I fibre distribution was lower in the immobilized leg than in the control leg. These results indicate that, following muscular hypotrophy resulting from 4-6 weeks of immobilization, dynamic exercise can restore the oxidative potential, whereas the size and strength are only partly recovered.

Maximum oxygen consumption rate and dihydrogenated ergot alkaloids in humans.

The relationship of maximal oxygen uptake (VO2 max) with dihydrogenated ergot alkaloids was investigated in twelve young men. They were subjected to graded bicycle exercise with work loads corresponding to 75% and 120% of the load necessary to elicit VO2 max. The exercise tests were performed after intravenous administration of 2 mg dihydroergostin (DE-145) as well as after saline as control, both preparations were given double-blind. VO2 max averaged (SD) 3.36 (0.41) 1/min and no significant difference was disclosed between the DE-145 and the control situation. Normal relationships were observed between VO2 and work load, ventilation, heart rate, cardiac output, central venous pressure and acid-base data, and these relations were unaffected by DE-145 administration. Nausea was constantly seen in all subjects tested with DE-145. It is concluded, that the present dose of DE-145 has no influence on the functional capacity of the oxygen transporting system in sedentary young men.

The epidermal growth factor-like domain of the human cartilage large aggregating proteoglycan, aggrecan: increased serum concentration in rheumatoid arthritis.

The large aggregating proteoglycan from human cartilage, aggrecan, has recently been shown to possess an immunologically detectable domain with close homology to epidermal growth factor (EGF), that is variably expressed by alternative mRNA splicing. Using a competitive ELISA we detected this domain in sera from both patients with RA and normal controls. The EGF-like domain could only be detected after digestion of sera with chondroitinase ABC, which demonstrates its proteoglycan origin. The concentration of the aggrecan EGF-like domain was considerably elevated in sera from patients with RA as compared to the control sera (P < 0.001), and the concentration of the domain increased with age in both the patient (r = 0.58, P < 0.05) and the control (r = 0.66, P < 0.01) group. These results demonstrate that the EGF-like domain of aggrecan could be of value as a marker of RA.

Skeletal muscle phosphagen and lactate concentrations in ischaemic dynamic exercise.

Five young males performed dynamic, submaximal contractions to exhaustion with the quadriceps muscle under arterial occlusion. The work load was 14.7 Watt (W). After 10 min rest with intact arterial circulation, the subjects commenced another bout to exhaustion; this process was repeated until a total of 10--16 bouts had been performed. Muscle biopsies were obtained immediately after the second, fifth, eighth, and last bout as well as 30 min after the last bout. The concentrations of adenosine triphosphate (ATP), creatine phosphate (CP), lactate, and glycogen were measured in each sample and some material underwent histochemical analysis. Muscle lactate was highest following the second work bout [22.9 mmol/kg wet weight (ww)] and gradually declined to 7.0 mmol/kg ww by the end of the last bout. CP level was low in all postexercise samples with the exception of a remarkably high CP (11.7 mmol/kg ww) after the last bout. Glycogen utilization tended to parallel muscle lactate levels, the rate of depletion being most rapid initially. Histochemical staining for glycogen depletion revealed that both type I and II fibres were low in glycogen, although type I was depleted most uniformly. In the first work bouts the high lactate and low CP levels in the total muscle could be responsible for the fatigue; none of these factors seem adequate to explain the development of the fatigue experienced in the later work bouts. It is concluded that muscle fatigue in this type of exercise is not related to substrate depletion or accumulation of metabolites, further that the fibre recruitment pattern is determined by the type and relative severity of performed work rather than local metabolic factors.