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Biomedical subjects

R H Edwards

Publications and source records attributed to R H Edwards.

At least 307 records · Page 17Linked to original sources

Aminophylline and fatigue of adductor pollicis in man.

1. The effect of intravenous aminophylline on the contractility of adductor pollicis has been studied in three subjects both in the fresh state and following the induction of muscle fatigue. 2. Aminophylline had no influence on the frequency-force relationship and relaxation rate of adductor pollicis in the fresh state. 3. Fatigue resulted in a selective depression of the force response to low and moderate frequencies of stimulation and a slight effect on maximum force production 10 and 35 min afterwards. 4. Aminophylline given prior to, during and/or after fatigue did not influence this selective low-frequency fatigue at 10 or 35 min. 5. Aminophylline at the concentrations obtained has no significant effect on muscle contractility or fatiguability in man.

Adult↗

Release of intracellular enzymes from an isolated mammalian skeletal muscle preparation.

An isolated skeletal muscle preparation is described which has been used to study the efflux of enzymes in response to contractile activity, metabolic poisons and detergent treatment. In both fast and slow muscles contractile activity caused a release of lactate dehydrogenase and creatine kinase that reached a peak 1-2 h after the end of stimulation. There was very little release during the 30 min stimulation period whether the muscles were under aerobic or hypoxic conditions. Incubation of the muscles with cyanide and iodoacetate caused a similar delayed release of enzyme. Disruption of cell membranes with detergent treatment caused an entirely different and very rapid pattern of enzyme release. Enzyme release from the fatigued isolated muscle preparations appears to be initiated as a consequence of phosphorylcreatine or ATP depletion. The relevance of this to release of muscle enzymes after activity in vivo is discussed.

Animals↗

The clinical presentation of hypothyroid myopathy and its relationship to abnormalities in structure and function of skeletal muscle.

Clinical assessment for the presence of myopathy was performed in fifteen untreated hypothyroid patients. In many of these patients plasma creatine kinase (CK) activities, tests of skeletal muscle function and vastus lateralis needle biopsies were performed. Muscle symptoms were extremely common, occurring in thirteen patients. Proximal muscle weakness, preferentially affecting the legs, muscle pains or cramps and delayed tendon jerk relaxation represented the commonest features of hypothyroid myopathy. Detailed descriptions are given of patients with muscle hypertrophy, muscle atrophy and developmental failure to illustrate the wide clinical spectrum. If examination revealed signs of myopathy, in particular if there was delayed relaxation of tendon jerks, biochemically severe hypothyroidism (serum thyroxine less than 20 nmol/l) was likely (P less than 0.01). The latter was a frequent finding in six patients with serous effusions (P less than 0.01). This subgroup also had a mean plasma CK activity of 1339 IU/l compared to 679 IU/l (normal 10-120 IU/l) for the whole hypothyroid group, and all five patients in this subgroup in whom vastus lateralis needle biopsies were performed showed abnormalities. Quadriceps force measurements and ankle jerk relaxation times were more sensitive than clinical examination in detecting muscle weakness and delayed relaxation. A reduced maximum relation rate (MRR) of the quadriceps, vastus lateralis needle biopsy abnormalities, and myopathic features on electromyography were characteristic.

Adolescent↗

Effect of treatment of Cushing's syndrome on skeletal muscle structure and function.

The time course of recovery in the myopathy of Cushing's syndrome was studied before and after removal of a pituitary adenoma at hypophysectomy in three patients and an adrenal adenoma in another. Serial measurements were performed of quadriceps force, total muscle mass/body weight, individual fibre size on needle biopsies of the lateral muscle mass of the thigh and skeletal muscle cross-sectional area (CSA) and force/unit CSA on computed (CT) scans of thighs and calves. All patients were weak, and recovery was slow but substantial except in one patient who had persistent Cushing's syndrome. An accompanying increase in overall and type II mean fibre area (MFA) occurred after surgery in the patients with a pituitary adenoma, as did an increase in skeletal muscle CSA and force/unit CSA in both patients having CT scans. The only patient with pronounced muscle wasting showed severe type II fibre atrophy with a reduced total muscle mass/body weight, but muscle morphology and total muscle mass were normal in the other patients. Only in this patient was a significant increase in total muscle mass/body weight noted after surgery. These findings suggest that the increase in muscle mass which may follow hypophysectomy in Cushing's syndrome is due to an increase in individual cell size.

Adult↗

Corticosteroid myopathy: a clinical and pathological study.

In six patients with Cushing's syndrome and three with steroid myopathy, the clinical, functional, biochemical and structural characteristics of myopathy are described. Proximal muscle weakness occurred in all the patients, preferentially affected the lower limbs and was accompanied by muscle wasting in all but one patient. Force measurements confirmed quadriceps weakness in every patient. Vastus lateralis muscle biopsies showed light microscopic abnormalities in two of three patients with steroid myopathy and one of five patients with Cushing's syndrome. Type II fibre atrophy was the commonest abnormality. Reduced type II mean fibre areas occurred in all the patients with steroid myopathy and were common in Cushing's syndrome patients. Type I mean fibre areas were also reduced in two of the former group and one of the latter group and two further patients in this group had areas at the lower end of the normal range. Abnormalities in electron microscopy, mitochondrial function tests and chemical content of skeletal muscle were frequent and are described and discussed. A plasma creatine kinase activity (CK) at the lower end of the normal range, a myopathic electromyogram (EMG) and a raised 24-h urinary 3-methylhistidine/creatinine ratio on a creatine free diet were other characteristic findings in both groups of patients.

Adolescent↗

The effect of high-resistance training on the strength and cross-sectional area of the human quadriceps.

Seventeen volunteers performed unilateral strength-training of the quadriceps with high-resistance, low-repetition, dynamic exercise, thrice weekly for an average of 5 weeks. Both before and after the training period, bilateral measurements were made of isometric quadriceps strength, quadriceps cross-sectional area (by ultrasound scanning), and thigh circumference. There were no significant changes in the untrained thighs. The trained quadriceps increased their isometric strength by more than they changed their cross-sectional area (mean increments = 15% and 6% respectively). Quadriceps hypertrophy was underestimated by measurements of thigh circumference and could not be predicted from them. We conclude that studies of localized muscle growth require direct measurements of the size of the muscle(s) concerned. Nevertheless, these may still underestimate the improvements in strength produced by high-resistance training.

Adult↗

Ultrasonic tissue characterisation of skeletal muscle.

Ultrasound techniques have been used for the non-invasive, quantitative characterisation of muscle tissue in normal subjects and volunteer patients. Radio frequency (RF) echoes from a volume of tissue have been digitised and analysed using computer techniques. Attention has been given to the correct positioning and orientation of the transducer during examination due to the importance of the angle dependence of the interaction of ultrasound with muscle fasciculi. Several different muscles in the leg, arm and back of normal subjects have been examined, whereas patient studies have concentrated on the vastus intermedius. Ultrasonic data from patients with muscular dystrophy have been correlated with measurements of muscle tissue density obtained using X-ray computerised tomography (X-ray CT). The technique shows that ultrasound can be used to differentiate between normal and diseased muscle quantitatively. Results indicate that pathological change can be detected and monitored earlier with ultrasound than with X-ray CT. These quantitative methods are now in use as a guide to the staging and monitoring of pathological change in muscle.

Fascia↗

Depressed protein synthesis is the dominant characteristic of muscle wasting and cachexia.

Wasting of skeletal muscle is a characteristic of many conditions besides those involving primary muscle disease, for example, cancer, cachexia and postoperative catabolism. There is now strong evidence from studies in animals, normal men and in patients with a variety of diseases to suggest that the muscle mass is regulated primarily by alterations in the protein synthetic rate and that changes in muscle protein degradation are largely secondary and adaptive. If this is so, attention should be focused on possible means of therapeutic intervention to increase protein synthesis rather than on ways of decreasing protein degradation.

Animals↗

Muscle morphology and metabolism in hypothyroid myopathy: effects of treatment.

Needle biopsies from vastus lateralis in untreated hypothyroid patients with muscle weakness confirmed by quadriceps force measurements (n = 11) were repeated when the patients had taken L-thyroxine for a mean period of 9.2 months (range 5.3-13.3 months, n = 8) and had been continuously biochemically euthyroid for a mean period of 4.9 months (range 2-11 months). Biopsies were analysed biochemically for mitochondrial function. On light microscopy, histochemical examination, mean fibre areas and fibre percentages of type I and type II fibres were determined. Electronmicroscopy was also performed. Abnormalities on light microscopy occurred in eight patients of which type II fibre atrophy was the commonest and of the remainder two patients showed a myopathic electromyogram (EMG) and a raised plasma creatine kinase activity and one ultrastructural change on biopsy. After treatment resolution of pathological changes was often slow and half the patients had persistent abnormalities when rebiopsied. The type I mean fibre area was significantly increased in the eight hypothyroid females (p less than 0.05) and type II mean fibre areas tended to be low and in females this was significant (p less than 0.05). After treatment the type I mean fibre area was significantly reduced (p = 0.05). The type II mean fibre area also tended to fall but this was not significant (p greater than 0.05). No change in the fibre percentages occurred. A myopathic EMG, a raised plasma creatine kinase activity, ultrastructural changes and low mitochondrial enzyme activities on needle biopsy were other common findings and their significance is discussed.

Aged↗

The effect of knee injury on the number of muscle fibres in the human quadriceps femoris.

By means of ultrasound scanning, bilateral measurements of the cross-sectional area of the quadriceps muscle groups were made in 14 young adults with unilateral thigh muscle wasting after knee injury. Needle biopsy specimens from the lateral mass of the muscle were used to estimate the myofibre cross-sectional area for both quadriceps of each subject. 2. The cross-sectional area of the quadriceps of each patient's injured limb was always smaller than that of the contralateral muscle. The wasting was largely localized to the quadriceps, with relative sparing of the other thigh muscles. 3. None of the biopsies showed any abnormality apart from the reduction in fibre size. In each case, the injured limb's reduced quadriceps cross-sectional area was associated with a reduced mean fibre area. 4. The ratio of the cross-sectional area of a muscle to its mean fibre area is a reduced mean fibre area. 4. The ratio of the cross-sectional area of a muscle to its mean fibre area is a function of the number of fibres it contains. The ratio varied considerably from patient to patient but there was close agreement between the values obtained for the two limbs of each patient. 5. The quadriceps wasting produced by knee injury was due to muscle fibre atrophy. There was no evidence for a change in the number of fibres in the muscle.

Adult↗

Low-frequency fatigue in isolated skeletal muscles and the effects of methylxanthines.

1. A form of skeletal muscle fatigue was examined with isolated animal and human muscle preparations. The possibility that methylxanthines could overcome this was investigated. 2. Prolonged contractile activity resulted in a long-lasting impairment of force generation at low frequencies of stimulation at times when the force at higher frequencies had substantially recovered. This was seen with both fast-twitch and slow-twitch animal muscles and with samples of isolated human muscle. 3. The decrease in low-frequency force was due to a decrease in twitch amplitude, suggesting damage to the processes involved in excitation--contraction coupling. 4. Caffeine and theophylline at concentrations of 1 mmol/l rapidly and completely reversed the effects of this form of fatigue in both animal and human muscle preparations. 5. Agents that potentiate muscle force production could be an effective means of counteracting the effects of an important form of skeletal muscle fatigue, but a clinically useful compound would need to be more potent than the methylxanthines currently in use.

Animals↗