Kristian Overgaard

Investigations on the possibility of a thermic tumour therapy—I.: Short-wave treatment of a transplanted isologous mouse mammary carcinoma☆☆☆

Abstract The existing literature on studies of the inhibitory effect of moderate heat doses on malignant tumours is briefly reviewed. An experimental technique of heat treatment of mouse tumours in vivo under accurate control of the intratumoural temperature is described. In experiments with an isologous transplantable mouse mammary carcinoma, controlled application of a moderate heat dose led, in many cases, to a permanent cure of the transplanted tumour without causing any damage to the surrounding normal tissue. The necessary heat doses in the temperature range of 41·5 to 43·5°C are worked out revealing a definite relationship between temperature and exposure time. The heat treatment induces distinct histological changes in the tumour cells, whereas it does not cause any damage to the stromal and vascular cells in the tumour, or to the surrounding normal tissue. Immediately after the heat application, definite changes were revealed in the mitochondria and lysosomes of the tumour cells. These changes increased in intensity with the size of the heat dose and become more pronounced within a few hours or days. Within the first few hours, changes in the nuclei of the tumour cells and in chromosomal and nucleolar chromatin developed, with some variation in the individual cells. 24 hr after the application of a curative dose, all tumour cells showed severe injury. After smaller doses the reaction to the heat was less intense, with variations in the individual cells, and several tumour cells did not show any signs of lethal injury. Autolytic disintegration of the heat-damaged tumour cells occurs very rapidly. The connective tissue of the stroma increases markedly in volume, and a scar forms. The histological examination did not reveal all details of the process, but in the light of biochemical observations, it is reasonable to assume that the direct effect of heat is due to an elective activation of the acid hydrolases localized in the lysosomes of the tumour cells.

Protective effects of lactic acid on force production in rat skeletal muscle

1 During strenuous exercise lactic acid accumulates producing a reduction in muscle pH. In addition, exercise causes a loss of muscle K+ leading to an increased concentration of extracellular K+ ([K+]o). Individually, reduced pH and increased [K+]o have both been suggested to contribute to muscle fatigue. 2 To study the combined effect of these changes on muscle function, isolated rat soleus muscles were incubated at a [K+]o of 11 mm, which reduced tetanic force by 75 %. Subsequent addition of 20 mm lactic acid led, however, to an almost complete force recovery. A similar recovery was observed if pH was reduced by adding propionic acid or increasing the CO2 tension. 3 The recovery of force was associated with a recovery of muscle excitability as assessed from compound action potentials. In contrast, acidification had no effect on the membrane potential or the Ca2+ handling of the muscles. 4 It is concluded that acidification counteracts the depressing effects of elevated [K+]o on muscle excitability and force. Since intense exercise is associated with increased [K+]o, this indicates that, in contrast to the often suggested role for acidosis as a cause of muscle fatigue, acidosis may protect against fatigue. Moreover, it suggests that elevated [K+]o is of less importance for fatigue than indicated by previous studies on isolated muscles.

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.

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.

Relations between excitability and contractility in rat soleus muscle: role of the Na+-K+ pump and Na+/K+ gradients

1 The effects of reduced Na+/K+ gradients and Na+‐K+ pump stimulation on compound action potentials (M waves) and contractile force were examined in isolated rat soleus muscles stimulated through the nerve. 2 Exposure of muscles to buffer containing 85 mM Na+ and 9 mM K+ (85 Na+/9 K+ buffer) produced a 54 % decrease in M wave area and a 50 % decrease in tetanic force compared with control levels in standard buffer containing 147 mM Na+ and 4 mM K+. Subsequent stimulation of active Na+‐K+ transport, using the β2‐adrenoceptor agonist salbutamol, induced a marked recovery of M wave area and tetanic force (to 98 and 87 % of the control level, respectively). Similarly, stimulation of active Na+‐K+ transport with insulin induced a significant recovery of M wave area and tetanic force. 3 During equilibration with 85 Na+/9 K+ buffer and after addition of salbutamol there was a close linear correlation between M wave area and tetanic force (r= 0·92, P< 0·001). Similar correlations were found in muscles where tetrodotoxin was used to reduce excitability and in muscles fatigued by 120 s of continuous stimulation at a frequency of 30 Hz. 4 These results show a close correlation between excitability and tetanic force. Furthermore, in muscles depressed by a reduction in the Na+/K+ gradients, β‐adrenergic stimulation of the Na+‐K+ pump induces a recovery of excitability which can fully explain the previously demonstrated recovery of tetanic force following Na+‐K+ pump stimulation. Moreover, the data indicate that loss of excitability is an important factor in fatigue induced by high‐frequency (30 Hz) stimulation.

Effects of sprint interval training on VO2max and aerobic exercise performance: A systematic review and meta-analysis

Recently, several studies have examined whether low‐volume sprint interval training (SIT) may improve aerobic and metabolic function. The objective of this study was to systematically review the existing literature regarding the aerobic and metabolic effects of SIT in healthy sedentary or recreationally active adults. A systematic literature search was performed (Bibliotek.dk, SPORTDiscus, Embase, PEDro, SveMed+, and Pubmed). Meta‐analytical procedures were applied evaluating effects on maximal oxygen consumption (VO2max). Nineteen unique studies [four randomized controlled trials (RCTs), nine matched‐controlled trials and six noncontrolled studies] were identified, evaluating SIT interventions lasting 2–8 weeks. Strong evidence support improvements of aerobic exercise performance and VO2max following SIT. A meta‐analysis across 13 studies evaluating effects of SIT on VO2max showed a weighted mean effects size of g = 0.63 95% CI (0.39; 0.87) and VO2max increases of 4.2–13.4%. Solid evidence support peripheral adaptations known to increase the oxidative potential of the muscle following SIT, whereas evidence regarding central adaptations was limited and equivocal. Some evidence indicated changes in substrate oxidation at rest and during exercise as well as improved glycemic control and insulin sensitivity following SIT. In conclusion, strong evidence support improvement of aerobic exercise performance and VO2max following SIT, which coincides with peripheral muscular adaptations. Future RCTs on long‐term SIT and underlying mechanisms are warranted.

Worksite interventions for preventing physical deterioration among employees in job-groups with high physical work demands: Background, design and conceptual model of FINALE

BackgroundA mismatch between individual physical capacities and physical work demands enhance the risk for musculoskeletal disorders, poor work ability and sickness absence, termed physical deterioration. However, effective intervention strategies for preventing physical deterioration in job groups with high physical demands remains to be established. This paper describes the background, design and conceptual model of the FINALE programme, a framework for health promoting interventions at 4 Danish job groups (i.e. cleaners, health-care workers, construction workers and industrial workers) characterized by high physical work demands, musculoskeletal disorders, poor work ability and sickness absence.Methods/DesignA novel approach of the FINALE programme is that the interventions, i.e. 3 randomized controlled trials (RCT) and 1 exploratory case-control study are tailored to the physical work demands, physical capacities and health profile of workers in each job-group. The RCT among cleaners, characterized by repetitive work tasks and musculoskeletal disorders, aims at making the cleaners less susceptible to musculoskeletal disorders by physical coordination training or cognitive behavioral theory based training (CBTr). Because health-care workers are reported to have high prevalence of overweight and heavy lifts, the aim of the RCT is long-term weight-loss by combined physical exercise training, CBTr and diet. Construction work, characterized by heavy lifting, pushing and pulling, the RCT aims at improving physical capacity and promoting musculoskeletal and cardiovascular health. At the industrial work-place characterized by repetitive work tasks, the intervention aims at reducing physical exertion and musculoskeletal disorders by combined physical exercise training, CBTr and participatory ergonomics. The overall aim of the FINALE programme is to improve the safety margin between individual resources (i.e. physical capacities, and cognitive and behavioral skills) and physical work demands, and thereby reduce the physical deterioration in a long term perspective by interventions tailored for each respective job-group.DiscussionThe FINALE programme has the potential to provide evidence-based knowledge of significant importance for public health policy and health promotion strategies for employees at high risk for physical deterioration.Trial registrationsISRCTN96241850, NCT01015716 and NCT01007669

Changes in Calpain Activity, Muscle Structure, and Function after Eccentric Exercise

PURPOSE The aim of this study was to investigate changes in muscle function, muscle structure, and calpain activity after high-force eccentric exercise. METHODS Eleven healthy males performed 300 maximal voluntary eccentric actions with knee extensors in one leg. Maximal force-generating capacity was measured before exercise and regularly during the next 7 d. Biopsies from musculus vastus lateralis were taken in both control and exercised legs 0.5, 4, 8, 24, 96, and 168 h after exercise for evaluation of myofibrillar structure, extracellular matrix proteins, and calpain activity. RESULTS In the exercised leg, peak torque was reduced by 47 +/- 5% during exercise and was still 22 +/- 5% lower than baseline 4 d after the exercise. Calpain activity was three times higher in the exercised leg compared with the control leg 30 min after exercise. Myofibrillar disruptions were observed in 36 +/- 6% of all fibers in exercised muscle and in 2 +/- 1% of fibers in control muscle. The individual reductions in peak torque correlated with the proportion of fibers with myofibrillar disruptions (r = 0.89). The increase in calpain activity was not correlated to the proportion of fibers with myofibrillar disruptions. Nevertheless, the characteristics of the myofibrillar disruptions mimicked calpain-mediated degradation of myofibrils. Tenascin-C and the N-terminal propeptide of procollagen type III showed increased staining intensity on cross-sections 4-7 d after the exercise. CONCLUSIONS Myofibrillar disruptions seem to be a main cause for the long-lasting reduction in force-generating capacity after high-force eccentric exercise. The increase in calpain activity, but the lack of a relationship between calpain activity and the amount of muscle damage, suggests multiple roles of calpain in the damage and repair process.

Diet, physical exercise and cognitive behavioral training as a combined workplace based intervention to reduce body weight and increase physical capacity in health care workers - a randomized controlled trial

BackgroundHealth care workers comprise a high-risk workgroup with respect to deterioration and early retirement. There is high prevalence of obesity and many of the workers are overweight. Together, these factors play a significant role in the health-related problems within this sector. The present study evaluates the effects of the first 3-months of a cluster randomized controlled lifestyle intervention among health care workers. The intervention addresses body weight, general health variables, physical capacity and musculoskeletal pain.Methods98 female, overweight health care workers were cluster-randomized to an intervention group or a reference group. The intervention consisted of an individually dietary plan with an energy deficit of 1200 kcal/day (15 min/hour), strengthening exercises (15 min/hour) and cognitive behavioral training (30 min/hour) during working hours 1 hour/week. Leisure time aerobic fitness was planned for 2 hour/week. The reference group was offered monthly oral presentations. Body weight, BMI, body fat percentage (bioimpedance), waist circumference, blood pressure, musculoskeletal pain, maximal oxygen uptake (maximal bicycle test), and isometric maximal muscle strength of 3 body regions were measured before and after the intervention period.ResultsIn an intention-to-treat analysis from pre to post tests, the intervention group significantly reduced body weight with 3.6 kg (p < 0.001), BMI from 30.5 to 29.2 (p < 0.001), body fat percentage from 40.9 to 39.3 (p < 0.001), waist circumference from 99.7 to 95.5 cm (p < 0.001) and blood pressure from 134/85 to 127/80 mmHg (p < 0.001), with significant difference between the intervention and control group (p < 0.001) on all measures. No effect of intervention was found in musculoskeletal pain, maximal oxygen uptake and muscle strength, but on aerobic fitness.ConclusionThe significantly reduced body weight, body fat, waist circumference and blood pressure as well as increased aerobic fitness in the intervention group show the great potential of workplace health promotion among this high-risk workgroup. Long-term effects of the intervention remain to be investigated.Trial registrationClinicalTrials.gov: NCT01015716

Muscle adaptations to plyometric vs. resistance training in untrained young men.

Vissing, K, Brink, M, Lønbro, S, Sørensen, H, Overgaard, K, Danborg, K, Mortensen, J, Elstrøm, O, Rosenhøj, N, Ringgaard, S, Andersen, JL, and Aagaard, P. Muscle adaptations to plyometric vs. resistance training in untrained young men. J Strength Cond Res 22(6): 1799-1810, 2008-The purpose of this study was to compare changes in muscle strength, power, and morphology induced by conventional strength training vs. plyometric training of equal time and effort requirements. Young, untrained men performed 12 weeks of progressive conventional resistance training (CRT, n = 8) or plyometric training (PT, n = 7). Tests before and after training included one-repetition maximum (1 RM) incline leg press, 3 RM knee extension, and 1 RM knee flexion, countermovement jumping (CMJ), and ballistic incline leg press. Also, before and after training, magnetic resonance imaging scanning was performed for the thigh, and a muscle biopsy was sampled from the vastus lateralis muscle. Muscle strength increased by approximately 20-30% (1-3 RM tests) (p < 0.001), with CRT showing 50% greater improvement in hamstring strength than PT (p < 0.01). Plyometric training increased maximum CMJ height (10%) and maximal power (Pmax; 9%) during CMJ (p < 0.01) and Pmax in ballistic leg press (17%) (p < 0.001). This was far greater than for CRT (p < 0.01), which only increased Pmax during the ballistic leg press (4%) (p < 0.05). Quadriceps, hamstring, and adductor whole-muscle cross-sectional area (CSA) increased equally (7-10%) with CRT and PT (p < 0.001). For fiber CSA analysis, some of the biopsies had to be omitted. Type I and IIa fiber CSA increased in CRT (n = 4) by 32 and 49%, respectively (p < 0.05), whereas no significant changes occurred for PT (n = 5). Myosin heavy-chain IIX content decreased from 11 to 6%, with no difference between CRT and PT. In conclusion, gross muscle size increased both by PT and CRT, whereas only CRT seemed to increase muscle fiber CSA. Gains in maximal muscle strength were essentially similar between groups, whereas muscle power increased almost exclusively with PT training.