Interaction of chemical with electromechanical factors in human skeletal muscle fatigue.
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Adenosine Triphosphate↗
Biomedical subjects
R H Edwards
Publications and source records attributed to R H Edwards.
Modern methods of diagnosis of muscle diseases.
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Adolescent↗
Electron spin resonance studies of intact mammalian skeletal muscle.
Samples of skeletal muscle from mice, rats and man have been examined by conventional electron spin resonance techniques. One major free-radical signal with g value 2.0036-2.004 was detected in all intact muscle samples and homogenates at 77 K whereas this signal was not seen at room temperature. Other less prominant signals were also detected. Thirty minutes of excessive contractile activity of rat hind limb muscles was found to result in a leakage of intracellular creatine kinase enzyme into the blood plasma and also produced an average 70% increase in the amplitude of the major electron spin resonance signal. These data support the hypothesis that increased free-radical activity may play some role in muscle damage caused by extensive muscular activity.
Animals↗
Measurements of calcium and other elements in muscle biopsy samples from patients with Duchenne muscular dystrophy.
The calcium, magnesium, sodium and potassium content of needle biopsy samples of human muscle from control subjects and patients with various neuromuscular disorders has been analysed by atomic absorption spectrometry. The calcium content of muscle from both patients with Duchenne Muscular Dystrophy and other myopathies was significantly elevated compared to both normal and patient control subjects. Muscle sodium content was not significantly altered in any group compared to control subjects. Decreased magnesium and potassium levels were found in muscle from patients with Duchenne Muscular Dystrophy, although the muscle magnesium/potassium ratio was unchanged, the most likely explanation for this being non-specific loss of intracellular components from the cell.
Biopsy, Needle↗
In vivo estimation of muscle protein synthesis in myotonic dystrophy.
The rate of muscle protein synthesis in patients with myotonic dystrophy has been studied, and results correlated with total muscle mass. Whole body and skeletal muscle protein synthesis were estimated by stable isotope methodology with a primed, continuous infusion of 1-[13C]leucine with measurement of incorporation of [13C]leucine into muscle protein in biopsy samples. Whole body leucine flux, protein synthesis, and protein breakdown were only slightly depressed, but muscle protein synthesis was markedly decreased, in myotonic dystrophy. This depression of muscle protein synthesis in myotonic dystrophy correlates with previous observations of impaired insulin-induced muscle uptake of amino acids and supports the suggestion that muscle wasting in this disease is the consequence of defective anabolism in muscle.
Adolescent↗
Vitamin E and muscle diseases.
Studies of the basic biochemical mechanisms underlying muscle damage aimed at finding agents which might reduce the amount of damage occurring in muscular dystrophy and other severe myopathies have been performed. These have suggested three types of agent which might be useful for this purpose, namely calcium antagonists, phospholipase inhibitors, and antioxidants or scavengers of reactive-free radicals. Vitamin E falls into the latter of these three categories and has been shown to reduce the amount of damage which occurs in isolated skeletal muscles following a given stress. It is suggested that, in the absence of calcium antagonists having relatively specific and effective actions on skeletal muscle or suitable inhibitors of muscle phospholipases in man, therapy with vitamin E or other antioxidants may reduce the amount of muscle damage occurring in patients with severe myopathies.
Calcium↗
Total body potassium and water, and exchangeable sodium, in muscular dystrophy.
Total body potassium (40K method) and total body water and exchangeable sodium (both by isotope dilution) were determined in 26 boys, aged 5-17 years, with muscular dystrophy. Total body potassium values were compared with measurements in a large series of normal boys on the basis of height. Total body potassium was reduced even in the youngest patients and was only slightly higher in the older boys, despite their considerably greater height. Exchangeable sodium increased with increasing height in a way similar to that of normal boys. Total body water was also reduced but increased with growth, although to a lesser extent than expected for normal boys. The total body water measurements indicated that many of the affected boys were very obese, despite an apparently normal body weight. An intravenous bolus of 22Na distributed at a similar rate in boys with muscular dystrophy to that in normal males. In relation to the predicted values, total body potassium and 24 h urinary creatinine excretion of the affected boys both declined at a rate of 4% per year.
Adipose Tissue↗
Topical magnetic resonance for the study of muscle metabolism in human myopathy.
The role of changes in energy metabolism are obvious in the myopathies with described enzyme defects, but the ability afforded by topical magnetic resonance spectroscopy to study these changes repeatedly and non-invasively helps provide an understanding of the alterations in energy metabolism seen in muscle complaints of which the aetiologies are still unclear. Attention is focused on interpreting the findings with particular regard to Duchenne muscular dystrophy.
Adult↗
Cytomegalovirus meningoencephalitis in a homosexual man with Kaposi's sarcoma: isolation of CMV from CSF cells.
A 36-year-old homosexual man developed a lymphocytic meningoencephalitis, lymphadenopathy, decreased helper/suppressor ratio in peripheral blood, and Kaposi's sarcoma. After repetitive evaluations for bacterial and fungal agents were negative, viral cultures were positive for cytomegalovirus. Virus was isolated only from CSF cells obtained from a large volume of fresh CSF. We present this case to document the association of CMV meningoencephalitis and acquired immunodeficiency syndrome (AIDS), and to emphasize that aggressive attempts to isolate CMV from CSF cells may be warranted in undiagnosed meningoencephalitis in patients at risk for AIDS.
Acquired Immunodeficiency Syndrome↗
Protein synthesis in muscle measured in vivo in cachectic patients with cancer.
Rates of synthesis of protein were measured in vivo in skeletal muscle and in the whole body of cachectic patients with cancer and in normal healthy men, using a tracer infusion of leucine labelled with a stable isotope. Synthesis of protein in muscle was significantly reduced in the patients with cancer (0.030 v 0.198%/hour; p less than 0.01), whereas whole body rates of protein synthesis and degradation did not differ significantly between the two groups. Thus depression of synthesis of protein in muscle appeared to be the immediate cause of muscle wasting in cancerous cachexia. Any therapeutic intervention that aims at preventing the onset of cachexia should be designed to stimulate the synthesis of protein in muscle, and measurement of turnover of protein may be used to evaluate such treatment provided that rates of protein synthesis are measured directly in specific tissues.
Aged↗
Role of mechanical damage in pathogenesis of proximal myopathy in man.
No adequate explanation has as yet been provided for the predominant proximal and symmetrical distribution of skeletal muscle weakness and wasting in human myopathies. One obvious difference between proximal and distal muscles is that in their postural antigravity role the former are involved in eccentric contractions to a much greater extent than are the latter. Recent physiological studies have shown that eccentric contractions produce considerable muscle damage in normal healthy subjects. The damage starts in individual sarcomeres but becomes more extensive over 1-2 days, the progression probably being due to the stronger sarcomeres stretching the weaker, damaged sarcomeres during normal activity and/or to the enzyme degradation of myofibrillar proteins when muscle damage results in Ca++ inflow. As a muscle becomes weaker and unable to meet the functional demands made upon it the likelihood of accidental stretch becomes greater. The vicious circle of weakness, stretch, damage, and further weakness may be the reason why the proximal muscles, which normally function eccentrically to some degree, are the most severely affected in a wide range of myopathic disorders.
Biomechanical Phenomena↗
Hyperammonemic encephalopathy related to ureterosigmoidostomy.
Urinary diversion to the colon may produce a metabolic encephalopathy with elevated blood ammonia levels. The condition resembles hepatic encephalopathy but can occur without obvious liver disease. The patient described herein also had a computed tomographic scan showing diffuse brain swelling and superficial contrast enhancement. The condition responds rapidly to lowering of the blood ammonia level and requires a high level of suspicion for diagnosis in the patient who has undergone urinary diversion and has an unexplained metabolic encephalopathy.
Adult↗
New techniques for studying human muscle function, metabolism, and fatigue.
To analyze human muscle function, metabolism, and fatigue in both health and disease a variety of techniques may be employed. The most fundamental approach is the measurement of force, which may be generated by either voluntary or electrically stimulated contractions. More detailed information concerning the mechanisms of both weakness and fatigue can be obtained when the electromyogram is recorded simultaneously with force. The needle biopsy technique is recommended for the histological and histochemical examination of skeletal muscle. It has the advantage of being rapid and repeatable and has proved suitable for both diagnostic and follow-up purposes. Recently developed techniques allow the study of mitochondrial function and protein synthesis. Topical nuclear magnetic resonance spectroscopy is a new and exciting technique for the noninvasive study of muscle metabolism. The opportunities offered by this technique are largely complementary to others available and unlikely to replace them as diagnostic and monitoring tools.
Biopsy, Needle↗
31P NMR studies of resting muscle in normal human subjects.
Study of human tissues using 31P topical Magnetic Resonance is completely atraumatic; it allows simultaneous measurement of the concentrations of many important metabolites and of intracellular pH. In some critical situations, TMR yields more accurate results than those obtained by chemical analysis of tissue biopsies. We have shown that TMR can be calibrated to obtain quantitative measurements in human subjects. We have also shown that theories of control of glycolysis based on regulation by key metabolites of rate-limiting enzymes are inconsistent with the observed changes in intact muscle.
Adenosine Triphosphate↗
Muscle fatigue in myophosphorylase deficiency: power spectral analysis of the electromyogram.
It has been postulated that the power spectral shift in the surface EMG during fatigue is due to accumulation of muscle lactate. This hypothesis has been directly tested by measuring such shift in 3 patients with myophosphorylase deficiency who performed sustained isometric contractions of the quadriceps muscle. It was found that the spectral shift in these patients was greater than that in normal subjects, rendering lactate as a cause of this phenomenon very unlikely. The mechanism of excessive fatiguability in myophosphorylase deficiency is thought to be due to failure of excitation of the muscle membrane; further support for this postulate is provided and it is contended that accumulation of extracellular potassium ions may explain the phenomena of spectral shift in normals and myophosphorylase deficient patients and the excessive fatiguability in the latter.
Adult↗
Effect of treatment on skeletal muscle dysfunction in hypothyroidism.
Abnormalities in skeletal muscle function were characterized in 19 hypothyroid subjects and the extent and time course of recovery in these abnormalities after treatment determined. Slow muscle relaxation was observed on examination in 11 patients and 12 out of 16 patients had a reduced quadriceps maximum relaxation rate (MRR) and 11 out of 15 had a prolonged ankle jerk relaxation time (AJRT). Measurements of quadriceps force revealed significant muscle weakness when comparison with 15 age matched healthy subjects was made (P less than 0.001). This weakness was often not evident on clinical examination. A raised plasma creatine kinase (CK) activity was characteristic. With treatment the plasma CK activity and the AJRT rapidly became normal often long before the serum thyroid-stimulating hormone (TSH) was normal, but the quadriceps MRR was slower to recover. It was rarely normal before the serum TSH became normal. Weakness was slow to recover and seven patients remained weak at the end of the study despite being euthyroid for a mean period of 1 year, but strength increased modestly overall (P less than 0.01). The urinary creatinine/height index was unchanged, indicating that total muscle mass does not alter with therapy.
Adolescent↗
Fatty acid oxidation in mitochondria from needle biopsy samples of human skeletal muscle.
Activities for the oxidation of palmitoylcarnitine, of palmitoyl-CoA and of carnitine palmitoyltransferase were measured in mitochondria prepared from needle biopsy samples of human skeletal muscle. Results are presented for nine normal subjects and 18 patients in whom there was evidence of mitochondrial abnormality. Palmitoylcarnitine and palmitoyl-CoA oxidation were measured spectrophotometrically by following the reduction of added cytochrome c in the presence of cyanide. Because of large variations in the activities between subjects it was essential to express the three activities per unit of cytochrome c oxidase activity to demonstrate unambiguous specific alterations in the activities. In most of the patients the order of the three activities was similar to that in the normal subjects. However, in five cases the activity for palmitoylcarnitine oxidation was less than 4% of the mean normal value. In two of these patients, the low activity could be accounted for by very low (less than 10% normal) activity of carnitine palmitoyltransferase (CPT). In another two patients the activity of CPT was normal but that of palmitoyl-CoA dehydrogenase (a measure of beta-oxidation) was very low.
Carnitine O-Palmitoyltransferase↗
Experimental mouse muscle damage: the importance of external calcium.
The involvement of extracellular calcium in experimental muscle damage has been studied in an isolated mouse soleus muscle preparation. The enzyme efflux and ultrastructural damage seen after excessive contractile activity were markedly reduced when the extracellular calcium was withdrawn. Low extracellular calcium also protected against the large enzyme efflux seen after treatment with low concentrations of detergent. Treatment of the muscle with the calcium ionophore A 23187 caused significant release of enzyme from the muscle. Nifedipine did not prevent the enzyme release after stimulation and although in some circumstances verapamil appeared to have some protective effect this was probably due to a local anaesthetic action on the muscle and not to any specific effect on calcium movement. It is concluded that extracellular calcium is important in mediating at least the two forms of muscle damage studied here.
Animals↗