Muscle Force In Patients Research Articles

Effect of revascularization on lower extremity muscle function in combined type 2 diabetes and critical limb threatening ischemia.

Critical limb-threatening ischemia (CLTI) and type 2 diabetes (T2D) frequently co-exist and often with less favorable outcome after revascularization. The objective was to evaluate the effects of revascularization on muscle function, perfusion and mitochondrial respiration in patients with combined CLTI and T2D. A prospective translational observational study. Two groups of patients facing unilateral peripheral revascularization was included: Patients suffering from combined disease with CLTI+T2D (N.=14) and patients suffering from CLTI (N.=15). During pedal exercise testing, calf muscle perfusion was monitored with near-infrared spectroscopy (NIRS) and leg arterial volume flow in the common femoral artery with duplex ultrasound. Calf muscle biopsy and subsequent assessment of mitochondrial respiratory capacity on isolated muscle fibers was performed. Tests was performed before and six weeks after revascularization. After revascularization, patients CLTI+T2D improved in muscle force from 8.48 kg (CI: 7.49-9.46) to 13.11 kg (CI: 11.58-14.63), (P<0.001). Conversely, muscle force in patients suffering from non-diabetic CLTI decreased from 10.03 kg (CI: 9.1-10.96) to 9.73 kg (CI: 8.77-10.69), (P=0.042). Muscle oxygenation during exercise improved more in the CLTI+T2D group (6.36 µM/kg/s [CI: 5.71-7.01] compared to 2.11 µM/kg/s [CI:1.38-2.83] in the CLTI group; P=0.002). No improvement or difference between groups regarding mitochondrial function was detected. Patients with combined CLTI+T2D, had an unsuspected better effect of revascularization compared to patients with non-diabetic CLTI, in terms of increased muscle force and improved muscle perfusion. Further studies are needed to elucidate the apparent interaction of the CLTI and T2D syndromes.

Prediction of key genes and miRNAs responsible for loss of muscle force in patients during an acute exacerbation of chronic obstructive pulmonary disease.

The present study aimed to identify genes and microRNAs (miRNAs or miRs) that were abnormally expressed in the vastus lateralis muscle of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The gene expression profile of GSE10828 was downloaded from the Gene Expression Omnibus database, and this dataset was comprised of 4 samples from patients with AECOPD and 5 samples from patients with stable COPD. Differentially expressed genes (DEGs) were screened using the Limma package in R. A protein-protein interaction (PPI) network of DEGs was built based on the STRING database. Module analysis of the PPI network was performed using the ClusterONE plugin and functional analysis of DEGs was conducted using DAVID. Additionally, key miRNAs were enriched using gene set enrichment analysis (GSEA) software and a miR-gene regulatory network was constructed using Cytoscape software. In total, 166 up- and 129 downregulated DEGs associated with muscle weakness in AECOPD were screened. Among them, NCL, GOT1, TMOD1, TSPO, SOD2, NCL and PA2G4 were observed in the modules consisting of upregulated or downregulated genes. The upregulated DEGs in modules (including KLF6 and XRCC5) were enriched in GO terms associated with immune system development, whereas the downregulated DEGs were enriched in GO terms associated with cell death and muscle contraction. Additionally, 39 key AECOPD-related miRNAs were also predicted, including miR-1, miR-9 and miR-23a, miR-16 and miR-15a. In conclusion, DEGs (NCL, GOT1, SOD2, KLF6, XRCC5, TSPO and TMOD1) and miRNAs (such as miR-1, miR-9 and miR-23a) may be associated with the loss of muscle force in patients during an acute exacerbation of COPD which also may act as therapeutic targets in the treatment of AECOPD.

Effect of levosimendan on the contractility of muscle fibers from nemaline myopathy patients with mutations in the nebulin gene

BackgroundNemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is characterized by generalized skeletal muscle weakness, often from birth. To date, no therapy exists that enhances the contractile strength of muscles of NM patients. Mutations in NEB, encoding the giant protein nebulin, are the most common cause of NM. The pathophysiology of muscle weakness in NM patients with NEB mutations (NEB-NM) includes a lower calcium-sensitivity of force generation. We propose that the lower calcium-sensitivity of force generation in NEB-NM offers a therapeutic target. Levosimendan is a calcium sensitizer that is approved for use in humans and has been developed to target cardiac muscle fibers. It exerts its effect through binding to slow skeletal/cardiac troponin C. As slow skeletal/cardiac troponin C is also the dominant troponin C isoform in slow-twitch skeletal muscle fibers, we hypothesized that levosimendan improves slow-twitch muscle fiber strength at submaximal levels of activation in patients with NEB-NM.MethodsTo test whether levosimendan affects force production, permeabilized slow-twitch muscle fibers isolated from biopsies of NEB-NM patients and controls were exposed to levosimendan and the force response was measured.ResultsNo effect of levosimendan on muscle fiber force in NEB-NM and control skeletal muscle fibers was found, both at a submaximal calcium level using incremental levosimendan concentrations, and at incremental calcium concentrations in the presence of levosimendan. In contrast, levosimendan did significantly increase the calcium-sensitivity of force in human single cardiomyocytes. Protein analysis confirmed that the slow skeletal/cardiac troponin C isoform was present in the skeletal muscle fibers tested.ConclusionsThese findings indicate that levosimendan does not improve the contractility in human skeletal muscle fibers, and do not provide rationale for using levosimendan as a therapeutic to restore muscle weakness in NEB-NM patients. We stress the importance of searching for compounds that improve the calcium-sensitivity of force generation of slow-twitch muscle fibers. Such compounds provide an appealing approach to restore muscle force in patients with NEB-NM, and also in patients with other neuromuscular disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-015-0037-7) contains supplementary material, which is available to authorized users.

Immediate Effects of Counterforce Forearm Brace on Grip Strength and Wrist Extension Force in Patients with Lateral Epicondylosis

Objective Although the effectiveness of counterforce braces has been reported in patients with lateral epicondylosis over the elbow, its immediate effect is limited. This research was to study the immediate effects of counterforce forearm brace on grip strength and wrist extension force in patients. Methods Fifteen patients (9 women and 6 men) with lateral epicondylosis (M ± SD, 8.1 ± 1.1 weeks) on their dominant arm participated in this study. We tested grip strength, wrist extension muscle force and range of motion (ROM) wrist extension immediately after application of counterforce forearm brace in the affected and unaffected arms. Results Among the variables, significant differences were found in grip strength (p =.02) and wrist extension muscle force (p =.001), but changes in ROM of wrist extension were not statistically significant (p = .98). Conclusion Using the counterforce forearm brace increased the rate of grip strength and wrist extension muscle force in patients with lateral epicondylosis. However, our findings did not support the use of the counterforce brace in increasing ROM in wrist extension.

Immediate Effects of Counterforce Forearm Brace on Grip Strength and Wrist Extension Force in Patients With Lateral Epicondylosis

Although the effectiveness of counterforce braces has been reported in patients with lateral epicondylosis over the elbow, its immediate effect is limited. This research was to study the immediate effects of counterforce forearm brace on grip strength and wrist extension force in patients. Fifteen patients (9 women and 6 men) with lateral epicondylosis ( M ± SD , 8.1 ± 1.1 weeks) on their dominant arm participated in this study. We tested grip strength, wrist extension muscle force and range of motion (ROM) wrist extension immediately after application of counterforce forearm brace in the affected and unaffected arms. Among the variables, significant differences were found in grip strength ( p = .02) and wrist extension muscle force ( p = .001), but changes in ROM of wrist extension were not statistically significant ( p = .98). Using the counterforce forearm brace increased the rate of grip strength and wrist extension muscle force in patients with lateral epicondylosis. However, our findings did not support the use of the counterforce brace in increasing ROM in wrist extension.

Vascular Progenitor Cells in Diabetes Mellitus

See related article, pages 1095–1102 Over the centuries, diabetes mellitus–associated ischemic ulcers have driven physicians to continue to improve their skills in healing the ulcers to prevent devastating complications.1 Unfortunately, extremity amputation still remains the outcome in many cases. The recent development of vascular progenitor cell (PC) transplantation aimed at enhancing angiogenesis and wound healing may, however, provide new hope in the treatment of this old ailment.2,3 In this issue of Circulation Research , Barcelos et al show in a murine diabetes mellitus model that topical transplantation of human fetal CD133+ PCs significantly accelerates the healing of skin wounds on ischemic hind limbs.4 Their data suggest that the reparative angiogenesis is mediated by the wingless (Wnt) signaling pathway. The prominin-1 (PROM1)/CD133 gene encodes a pentaspan transmembrane glycoprotein expressed in a variety of stem cells, including hematopoietic stem cells, endothelial PCs (EPCs), and neuronal/glial stem cells.5,6 By suppressing further differentiation, PROM1 helps these cells maintain their stem cell properties. Mutations in PROM1 may result in retinitis pigmentosa,7 and its overexpression is also associated with cancer formation.8 In view of this cancer potential, overstimulation of CD133+ cells may also lead to unwanted consequences. Additionally, that human fetal CD133+ cells are not easily accessible …

Markers of inflammation and disuse in vastus lateralis of chronic obstructive pulmonary disease patients

Disuse and/or local inflammation in the muscle cannot be excluded as potential influences for the decreased muscle force in patients hospitalised due to an acute chronic obstructive pulmonary disease (COPD) exacerbation. This study aims to compare expression levels of markers of disuse (insulin-like growth factor-1 (IGF-I), MyoD and myogenin) and inflammation [interleukin-6 (IL-6), IL-8 and tumour necrosis factor-alpha (TNF-alpha)] in the muscle of hospitalised and stable COPD patients and healthy elderly. Muscle biopsies (m. vastus lateralis) were taken in 14 hospitalised COPD patients (aged 68 +/- 8), 11 clinically stable COPD patients (aged 68 +/- 9) and seven healthy subjects (aged 70 +/- 7) to analyse local mRNA expression levels of IL-6, IL-8, TNF-alpha, IGF-I and protein expression levels of IGF-I, MyoD and myogenin. Relationships of these expression levels with lung and skeletal muscle function were investigated. IGF-I mRNA and MyoD protein levels were significantly lower in hospitalised patients compared to healthy subjects. MyoD protein levels were positively related to quadriceps force. Muscle IL-6 and IL-8 expression in hospitalised patients was similar compared to stable patients and healthy subjects and was not related to expression levels of muscle markers of disuse or quadriceps force. Muscle TNF-alpha and myogenin were not detected. Decreased expression levels of muscle IGF-I and MyoD in hospitalised patients suggest a potential influence of disuse in the increased muscle weakness during an acute COPD exacerbation. This study did not find any evidence supporting local inflammation via IL-6, IL-8 and/or TNF-alpha in the vastus lateralis muscle of COPD patients.

Aberrations in the control of quadriceps muscle force in patients with knee osteoarthritis.

To characterize the distribution of error in knee joint proprioception, quadriceps force accuracy and steadiness, and muscle strength in patients with knee osteoarthritis (OA). Special attention was paid to eccentric strength. We compared knee OA patients (n=20: 15 women, 5 men) with age- and sex-matched, symptom-free adults. Knee pain and mobility were assessed with standard tests. Knee joint proprioception was measured with a repositioning test. Quadriceps force accuracy and steadiness were determined during a force target-tracking task. Maximal voluntary quadriceps force was measured during eccentric, isometric, and concentric contractions. OA patients had knee pain, needed 67% more time to complete 4 functional tasks, and produced 82% more proprioception errors (all P < 0.05). About 80% of this error was due to overshooting the target and 68% of the overshooting error occurred at 2 of the 5 least flexed knee joint positions. OA patients had 89% more errors in accurately matching target forces during submaximal quadriceps contractions and in the same tasks, OA patients also produced these forces with 155% more variability (all P < 0.05). OA patients had especially weakened ability to produce maximal voluntary eccentric strength. Quadriceps dysfunction in knee OA includes impaired proprioception, especially in the more extended knee joint positions; impaired ability to accurately and steadily control submaximal force; and impaired eccentric strength. These results have implications for designing exercise and rehabilitation programs for patients with knee OA.

Sensation of respiratory force following low cervical spinal cord transection.

The psychophysical technique of magnitude scaling was used to assess the sensation of respiratory muscle force in patients with low cervical spinal cord transection. The exponents of the power function relationship between load magnitude and sensation intensity during graded elastic and resistive ventilatory loading in the quadriplegic patients were 0.51 and 0.54, respectively. These values were significantly lower than those in normal subjects (P less than 0.05). This impairment in load sensation could not be attributed to differences in either the duration or magnitude of the forces generated by muscles of inspiration during loading, since the power function relationships between airway pressure and sensation intensity corrected for inspiratory duration were also significantly lower in the quadriplegic patients compared with the normal subjects. In contrast the perception of respiratory force during inspiratory maneuvers against a closed airway, as determined by both magnitude estimation and production tests, was the same in normal subjects and quadriplegics. These results suggest that afferent signals from rib cage receptors are important in shaping the intensity of the sensation during submaximal ventilatory loading. During maximal loading, i.e., airway occlusion, when respiratory muscle tension changes proportionally with the motor command, centrally generated efferent command signals may be employed to subserve the sensation of respiratory muscle force when inputs from rib cage muscle receptors are not available.

Integrated electrical activity and number of zero crossings during a gradual increase in muscle force in patients with neuromuscular diseases

In the brachial biceps muscle of 17 patients with myopathy and of 14 patients with neurogenic disorders the integrated electrical activity and number of zero crossings per unit time were analysed in 3 sites of each muscle every 100 msec during a gradual increase in force from zero to maximum within 10 sec. The analysis of integrated electrical activity could not discriminate between patients with myopathy and patients with neurogenic disorders. The slope of the linear relation between the square root of integrated electrical activity and force expressed in kilograms was increased in 44% of the patients with myopathy and in 64% of the patients with neurogenic disorders. The increase in slope may be due to increase in the ratio of electrical activity and force of individual motor units. The integrated electrical activity related to a force of 40% of maximum was decreased in about two-thirds of patients with myopathy and in about half of the patients with neurogenic disorders. This decrease in integrated electrical activity may be due to random loss of muscle fibres or to loss of whole motor units respectively. The integrated electrical activity was linearly related to mean amplitude between potential reversals per unit time (turns). The number of zero crossings was increased in 29% of the patients with myopathy and decreased in 70% of the patients with neurogenic disorders at a force of 30% of maximum. The number of zero crossings was linearly related to turns. When the results from integrated activity and zero crossing were compared to those of the analysis of turns, mean amplitude and the ratio between them, the latter method was best to discriminate patients with neuromuscular disease from controls.