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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using an animal model of limb distraction, the extent of muscle fibre damage and atrophy resulting from distraction at two different rates (1.3 or 3.0 mm day(-1)) was investigated. It was found that at the high rate of distraction there was a significantly greater loss of range of joint movement and more muscle fibre atrophy and fibre damage than at the low rate. Muscle fibre damage is usually followed by regeneration. This involves the expression of the neonatal form of myosin heavy chain, which can therefore be used as an indicator of regeneration. It was found that whilst many more fibres showed evidence of damage at the high compared to the low rate, the number of fibres expressing neonatal myosin was significantly reduced, indicating the presence of a population of fibres which was undergoing degeneration without subsequent regeneration. Thus it would appear that beyond a certain rate of distraction, regeneration may be insufficient to replace contractile material damaged by overstretching. It is suggested that these fibres are replaced with connective tissue. This process may contribute to the muscle weakness and loss of range of joint movement which sometimes accompanies limb distraction procedures.
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PMID:Muscle fibre damage and regeneration resulting from surgical limb distraction. 1149 Jan 19

1. Ageing is generally associated with a decline in skeletal muscle mass and strength and a slowing of muscle contraction, factors that impact upon the quality of life for the elderly. The mechanisms underlying this age-related muscle weakness have not been fully resolved. The purpose of the present study was to determine whether the decrease in muscle force as a consequence of age could be attributed partly to a decrease in the number of cross-bridges participating during contraction. 2. Given that the rigor force is proportional to the approximate total number of interacting sites between the actin and myosin filaments, we tested the null hypothesis that the rigor force of permeabilized muscle fibres from young and old rats would not be different. 3. Permeabilized fibres from the extensor digitorum longus (fast-twitch; EDL) and soleus (predominantly slow-twitch) muscles of young (6 months of age) and old (27 months of age) male F344 rats were activated in Ca2+-buffered solutions to determine force-pCa characteristics (where pCa = -log(10)[Ca2+]) and then in solutions lacking ATP and Ca2+ to determine rigor force levels. 4. The rigor forces for EDL and soleus muscle fibres were not different between young and old rats, indicating that the approximate total number of cross-bridges that can be formed between filaments did not decline with age. We conclude that the age-related decrease in force output is more likely attributed to a decrease in the force per cross-bridge and/or decreases in the efficiency of excitation-contraction coupling.
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PMID:Rigor force responses of permeabilized fibres from fast and slow skeletal muscles of aged rats. 1155 38

Acute quadriplegic myopathy with loss of thick (myosin) filaments (AQM-LTF) is an acute toxic myopathy observed in critically ill patients and is characterized by proximal or diffuse weakness of extremities and difficulty in weaning from mechanical ventilation. In recent years, this myopathy has been described in transplanted patients, although only 5 cases have been reported following heart transplantation. We present 3 new cases and review the previous literature. We conclude that the clinical picture and outcome of AQM-LTF in heart-transplanted patients do not differ from those observed in other critically ill patients (transplanted and non-transplanted). Therefore, because AQM-LTF is often clinically suspected muscle biopsy should be quickly performed to confirm the diagnosis so that physical therapy may begin as soon as possible.
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PMID:Acute quadriplegic myopathy with loss of thick (myosin) filaments following heart transplantation. 1159 71

Sepsis may cause not only failure of parenchymal organs but can also cause damage to peripheral nerves and skeletal muscles. It is now recognized that sepsis-mediated disorders of the peripheral nerves and the muscle, called critical illness polyneuropathy (CIP) and critical illness myopathy, are responsible for weakness and muscle atrophy occurring de novo in intensively treated patients. CIP represents an acute axonal neuropathy that develops during treatment of severely ill patients and remits spontaneously, once the critical condition is under control. The course is monophasic and self-limiting. Among the critical illness myopathies, three main types have been identified: a non-necrotizing "cachectic" myopathy (critical illness myopathy in the strict sense), a myopathy with selective loss of myosin filaments ("thick filament myopathy") and an acute necrotizing myopathy of intensive care. Clinical manifestations of both critical illness myopathies and CIP include delayed weaning from the respirator, muscle weakness, and prolonging of the mobilization phase. The pathogenesis of these neuromuscular complications of sepsis is not understood in detail but most authors assume that the inflammatory factors that mediate systemic inflammatory response and multiple organ failure are closely involved. In thick filament myopathy and acute necrotizing myopathy, administration of steroids and neuromuscular blocking agents may act as triggers. Specific therapies have not been discovered. Stabilization of the underlying critical condition and elimination of sepsis appear to be of major importance. Steroids and muscle relaxants should be avoided or administered at the lowest dose possible.
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PMID:Neurological complications of sepsis: critical illness polyneuropathy and myopathy. 1175 54

Two siblings (patients 1 and 2) had adult-onset muscle weakness that was greater distally than proximally, as well as respiratory insufficiency, cardiomyopathy, and cervical spine anomalies. Electromyography studies indicated myopathy and findings consistent with neuropathy in both. In the deltoid muscle of patient 1 and the anterior tibial muscle of patient 2, myriad type 1 fibers harbored large, irregularly polygonal, and mostly central hyaline masses, small vacuoles, and nemaline rods flanking the hyaline masses or congregated under the sarcolemma. The hyaline masses are intensely congophilic; react strongly for desmin, alphaB-crystallin, alpha1-antichymotrypsin, and ubiquitin and variably for gelsolin and dystrophin; and are devoid of alpha-actinin, nebulin, titin, and slow myosin. The presence of ubiquitin, gelsolin, and fragmented filaments, and the absence of nebulin, titin, alpha-actinin, and slow myosin in the hyaline masses, signal nonlysosomal protein degradation. Ultrastructurally, the hyaline masses are composed of intermediate-density amorphous material intermingled with fragmented filaments and irregularly branching, pleomorphic, highly electron-dense material, resembling the hyaline structures of myofibrillar myopathy. We conclude that the pathological process in this syndrome is one that induces destruction of myofibrillar components, resulting in aggregation of the degraded residues in hyaline masses, and causes replication of Z disks, resulting in formation of nemaline rods.
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PMID:Familial cardioneuromyopathy with hyaline masses and nemaline rods: a novel phenotype. 1183 79

A number of patients admitted to intensive care units for non-neurological disorders develop neuromuscular complications. These patients present with an acute flaccid generalized weakness that may or may not be accompanied by sensory symptoms. There are two main conditions, namely critical illness polyneuropathy and neuromuscular disorder related to the use of neuromuscular blocking agents. These conditions differ in several ways. Critical illness polyneuropathy occurs usually after long stays (weeks) in intensive care units. It concerns patients presenting with a multiple organ dysfunction syndrome, and often sepsis. The polyneuropathy is axonal and implies both sensory and motor fibres. Its pathophysiology remains unclear. Mortality is as high as 60 p.cent and relates to the medical, rather than to the neurological condition. In survivors recovery may be complete, although over a period of months. Neuromuscular disorder related to the use of neuromuscular blocking agents occurs on average after 10 days. It most often concerns patients admitted to intensive care units for acute respiratory failure, mainly asthma or adult respiratory distress syndrome, that may require mechanical ventilation, use of neuromuscular blocking agents and steroids. A purely motor deficit is usually first noticed when curarisation is discontinued. Electromyography discloses fibrillation potentials in all muscles, as well as myopathic changes. Muscle biopsy demonstrates necrosis and a deficit in myosin filaments. In severe cases, injury to distal motor axons probably occurs. Recovery is usually excellent over a few weeks. Recently, replacement of neuromuscular blocking agents by sedatives has notably reduced the occurrence of this disorder. Critical illness neuropathies often cause difficulty in weaning patients from the respirator. They prolong the stay in the intensive care unit, thereby increasing the risks of complications for the patients. Course of these neuromuscular disorders is usually favorable, however sometimes with sequelae.
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PMID:[Critical illness neuropathies]. 1197 88

Four unrelated patients are reported with muscle hypotonia, weakness, skeletal dysmorphism and respiratory insufficiency since childhood. Muscle tissues were found to contain a number of muscle fibres with abnormal structure. Peripherally located structures such as a cap lacking in ATP-ase and fast myosin activity, rich in desmin, tropomyosin and alpha-actinin consisted of abnormally arranged myofibrils. The position of the peripherally situated myofibrils, as well as their abnormal sarcomere pattern, seems to point to an error in fusion and muscle protein synthesis. Whether our cases of congenital myopathy with cap structures are of hereditary origin or of a sporadic type remains unknown, so far. It seems that the result of our study, as well as data presented in the literature, allows us to divede cap disease into two forms: fatal and nonfatal. The morphological changes in the muscle fibres are identical in all the presented cases but the number of muscle fibres with cap structures is much higher in the fatal form.
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PMID:"Cap disease"--a failure in the correct muscle fibre formation. 1216 90

Acute myopathy is a common problem in intensive care units. Those at highest risk for developing critical illness myopathy are exposed to intravenous corticosteroids and paralytic agents during treatment of various illnesses. Diffuse weakness and failure to wean from mechanical ventilation are the most common clinical manifestations. Serum creatine kinase levels are variable. Electrodiagnostic studies reveal findings of a myopathic process, often with evidence of muscle membrane inexcitability. Based on animal model studies, the loss of muscle membrane excitability may be related to inactivation of sodium channels at the resting potential. In addition, human and animal pathologic studies reveal characteristic loss of myosin with relative preservation of other structural proteins. In some patients, there is also upregulation of proteolytic pathways, involving calpain and ubiquitin, in conjunction with increased apoptosis. Fortunately, the disorder is reversible, but there may be considerable morbidity.
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PMID:Critical illness myopathy. 1221 45

Neuromuscular weakness commonly develops in the setting of critical illness. This weakness delays recovery and often causes prolonged ventilator dependence. An axonal sensory-motor polyneuropathy, critical illness polyneuropathy (CIP), is seen in up to one third of critically ill patients with the systemic inflammatory response syndrome (usually due to sepsis). An acute myopathy, critical illness myopathy (CIM), frequently develops in a similar setting, often in association with the use of corticosteroids and/or nondepolarizing neuromuscular blocking agents. These patients are often difficult to evaluate due to the limitations imposed by the critical care setting and may be further complicated by the presence of both CIP and CIM in varying degrees. This paper reviews the clinical and electrophysiologic features of these disorders, as well as the putative pathophysiology. In the case of CIM, an animal model has provided evidence that weakness in this disorder is caused by muscle membrane inexcitability due to altered membrane sodium currents and loss of myosin thick filaments.
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PMID:Critical illness myopathy and polyneuropathy. 1235 8

Changes in intracellular Ca2+-concentration play an important role in the excitation-contraction-relaxation cycle of skeletal muscle. In this review we describe various inheritable muscle diseases to highlight the role of Ca2+-regulatory mechanisms. Upon excitation the ryanodine receptor releases Ca2+ in the cytosol. During and after contraction the sarcoplasmic reticulum (SR) Ca2+ATPase (SERCA) pumps Ca2+ back in the SR resulting in relaxation. An abnormal change in the intracellular Ca2+-concentration results in defective muscle contraction and/or relaxation, which is the cause of various muscle diseases. Malignant hyperthermia (MH) and central core disease (CCD) are both caused by mutations in the ryanodine receptor but show different clinical phenotypes. In MH an acute increase of Ca2+ results in excessive muscle contraction causing rigidity, while in CCD a chronic rise of cytosolic Ca2+ is seen, leading to mitochondrial damage, disorganization of myofibrils and muscle weakness. In Brody disease and also in mitochondrial myopathies, SERCA functions sub optimal causing a prolonged physiological Ca2+-elevation leading to slowing of relaxation. Defective actin-myosin interactions, as in nemaline myopathy and also in mitochondrial myopathies due to ATP-shortage, cause Ca2+-hyposensitivity and slowness of contraction. Information of Ca2+-kinetics in these inherited muscular diseases improves our understanding of the role of calcium in the physiology and pathophysiology of the skeletal muscle cell.
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PMID:Calcium regulation and muscle disease. 1236 86


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