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Biomedical subjects

R H Edwards

Publications and source records attributed to R H Edwards.

At least 325 records · Page 18Linked to original sources

Muscle protein synthesis measured by stable isotope techniques in man: the effects of feeding and fasting.

1. Measurements have been made of whole-body and skeletal muscle protein synthesis in fed and fasted adults with L-[1-13C]leucine. 2. The marked increase in whole-body synthesis on feeding largely reflects the changes in protein synthesis in muscle, which doubles on feeding, compared with a 40% increase in that of the rest of the body. 3. Skeletal muscle in fed man contributes more than half to total protein synthesis occurring in the whole body.

Adult↗

Tissue zinc levels as an index of body zinc status.

Dietary depletion of zinc was found to result in a 30% decrease in the total body zinc content of experimental rats when compared with control animals. In the depleted animals there was no decrease in the zinc content of hair, skin, heart or three different skeletal muscles although the levels in plasma, liver, bone, and testes were significantly reduced. The analysis of tissues from three patients suffering from disturbance of zinc metabolism suggest that man reacts to zinc deficiency in a similar way. These findings indicate that for a simple screening test of zinc status, analysis of the plasma zinc concentration remains the single most useful measurement.

Animals↗

The effect of temperature, ischaemia and contractile activity on the relaxation rate of human muscle.

The relaxation rate from electrically stimulated isometric contractions of human adductor pollicis has been measured during rewarming following cooling, during ischaemia and during ischaemic contractile activity. The Q10 for relaxation rate (25-37 degrees C intramuscular temperature) was estimated as 2 . 3. Relaxation rate was found to decline at a rate of 1 . 5% initial value per minute of ischaemia. Relaxation rate declined more rapidly during ischaemic contractile activity than during ischaemia alone. The rate of decline was more closely related to the force X time performed than the number of excitatory impulses. During a supramaximal 20 Hz tetanus, relaxation rate declined markedly at a time when only slight force fatigue had occurred; hence the decline could not be explained by selective fast muscle fibre fatigue. No recovery occurred during ischaemic rest following ischaemic activity but, following restoration of the circulation, recovery occurred with a half time of one minute being virtually complete at 5-7 min. Changes in relaxation rate during fatiguing contractions and recovery from them follow different time courses from muscle excitability and force production. Change in relaxation rate cannot be simply related to changes in the concentration of major energy metabolites. It is proposed that relaxation rate is related to the rate of energy turnover in the contracting muscle.

Adult↗

Metabolic heat production in isometric ischaemic contractions of human adductor pollicis.

The rate of intramuscular temperature rise (dT/dt) has been measured in ischaemic isometric contractions of adductor pollicis in man as an index of the rate of energy turnover. Experiments were designed so as to compare dT/dt in contractions made at a constant force but at differing intramuscular temperatures or degrees of ischaemic fatigue. In the same experiments relaxation rate was measured. As intramuscular temperature was raised from 25 to 37 degrees C, dT/dt increased with a Q10 of 1 . 8 and was closely correlated with relaxation rate. During constant force submaximal ischaemic contractions dT/dt fell, failed to recover with ischaemic rest but did so within 10 min of restoration of the circulation. During the fatiguing contraction and recovery thereafter dT/dt was linearly correlated with relaxation rate. The results show that the rate of energy turnover at a constant force is susceptible to change in association with alteration in the contractile speed of the muscle. It is suggested that relaxation rate may be used as an index of the capacity of the muscle to liberate energy.

Adult↗

A flexible microprocessor system for the measurement of cell size.

A flexible system for the measurement of length and area is described. The system consists of the Reichert Jung MOP-1 area measuring device interfaced with a Commodore PET computer. Its use is illustrated by the planimetric measurement of cross sectional areas in histochemical preparations of normal and diseased muscle. While measurements are being made data can be displayed on the computer screen either in numerical form or as a frequency histogram together with simple statistical analyses. Hard copy can be obtained from an attached printer. Mean values for fibre area in normal human skeletal muscle are reported. An alternative, widely used method of calculating fibre area from the lesser diameter was found to give a consistent underestimate of approximately 30% when compared with our planimetric method. In diseased muscle with abnormally shaped fibres the discrepancy is even larger; such fibres can be identified using a "form factor" which relates the area of a cell to its perimeter. This rapid, accurate and flexible system is also suitable for the measurement of many different types of graphical record.

Biopsy, Needle↗

Severe muscle cramps relieved by transcutaneous nerve stimulation: a case report.

The case is described of a 51-year-old man with a 21 year history of severe, long-lasting and widespread muscle cramps. Physical examination revealed muscle hypertrophy and fasciculation; electromyography showed spontaneously active motor units which disappeared during sleep. Cramps could be aborted by ice or mechanical vibration but the most effective management was achieved using transcutaenous nerve stimulation.

Biopsy, Needle↗

Changes in EMG power spectrum (high-to-low ratio) with force fatigue in humans.

During and following high-load fatiguing voluntary contractions, the force response of skeletal muscle to electrical stimulation is altered so that the frequency-force curve is moved to the right. Fatiguing contractions also result in a shift to the left of the electromyographic (EMG) power spectrum. In the quadriceps muscle and the diaphragm of normal subjects the change in the force response to electrical stimulation has been correlated with the EMG changes. After repeated submaximal contractions in the quadriceps and diaphragm, the forces produced by electrical stimulation at low frequencies were reduced, indicating low-frequency fatigue. This type of fatigue persisted for several hours but did not result in any change in the EMG high-to-low ratio. Low-frequency fatigue is probably an important aspect of the failure of skeletal muscle to generate adequate force, and the EMG high-to-low ratio may not recognize this type of fatigue.

Diaphragm↗

Regulation of leucine metabolism in man: a stable isotope study.

Leucine catabolism is regulated by either of the first two degradative steps: (reversible) transamination to the keto acid or subsequent decarboxylation. A method is described to measure rates of leucine transamination, reamination, and keto acid oxidation. The method is applied directly to humans by infusing the nonradioactive tracer, L-[15N,1-13C]leucine. Leucine transamination was found to be operating several times faster than the keto acid decarboxylation and to be of equal magnitude in adult human males under two different dietary conditions, postabsorptive and fed. These results indicate that decarboxylation, not transamination, is the rate-limiting step in normal human leucine metabolism.

Adult↗

Human muscle function and fatigue.

Fatigue is defined as a failure to maintain the required or expected force. The force of a voluntary contraction is graded according to both the tension generated in each muscle fibre and the number of fibres recruited. The same is true of fatigue. Percutaneous electrical stimulation of a muscle via its motor nerve allows the contractile function to be measured independently of volition. Studies have been made of the forces generated isometrically at different stimulation frequencies (frequency: force curve), and of fatiguability (tendency to lose force in a given time at specified stimulation frequencies), in the quadriceps and adductor pollicis muscles. Electrical stimulation recordings of the programmed stimulation myograms distinguish forms of muscle fatigue. Low frequency fatigue which implies impaired excitation-contraction coupling is long-lasting, whereas high frequency fatigue which represents impaired muscle membrane excitation recovers rapidly. Electromyographic (EMG) indicators of fatigue are well recognized but their use is limited because they cannot alone indicate whether alterations in excitation-contraction coupling underlie fatigue. Alterations in the power spectrum of the EMG precede (force) fatigue in sustained maximum voluntary contractions. Fatigue may ultimately be due to a failure of the rate of energy supply to meet demand, but the precise expression of this defect may vary, such that failure of excitation or of activation may predominate over failure of the energy supply.

Energy Metabolism↗

Contractile function and fatigue of the respiratory muscles in man.

Ventilation depends on the proper functioning of the respiratory muscles. These muscles, like other skeletal muscles, can endure high work loads for only short time periods. The work of breathing in patients with lung disease in increased and it has therefore been argued that respiratory muscle fatigue may develop and contribute to respiratory failure. We have studied the contractile function and fatigue of the sternomastoid muscle and the diaphragm in normal subjects and found that these respiratory muscles have the same contractile properties as limb muscles. If subjected to a high load they develop similar patterns of fatigue. Studies on the sternomastoid muscle in patients with lung disease also confirmed that respiratory stress produces fatigue.

Action Potentials↗

Fatigue in human metabolic myopathy.

The ability of muscle fibres to sustain force can be related to their economy of energy utilization and to their capacity to regenerate energy under the prevailing conditions (aerobic or anaerobic) of contraction. The pathophysiology of muscle fatigue is analysed in patients with thyroid dysfunction and with impaired glycogenolysis, and in a patient with abnormal mitochondrial function. Muscle from hypothyroid patients, like cooled muscle, is slow in relaxing and shows a reduced energy requirement (energy economy) and reduced fatiguability, whereas muscle of hyperthyroid patients may show the opposite features. In myophosphorylase deficiency the energy economy is normal in the fresh state and increases as contraction proceeds; however, fatigue is premature and associated with impaired excitation rather than an overall depletion of energy stores. With abnormal mitochondrial function the muscle tends to be effectively anaerobic and fatigue is associated with impaired excitation-contraction coupling. This appears to result from either muscle ischaemia or the dominant use of anaerobic metabolism for energy regeneration. Fatigue in these disorders of energy metabolism may ultimately be due to a reduced supply of ATP but direct evidence of this is lacking and, if it occurs, its physiological expression is probably variable.

Adenosine Triphosphate↗

Effect of exercise on protein turnover in man.

1. We have investigated the effects of moderate long-term exercise on protein turnover in fed man by measuring the extent of whole-body nitrogen production, the labelling of urinary ammonia from ingested [15N]glycine and plasma, muscle and urine free amino acid concentrations. 2. Judged both from nitrogen production, and from the extent of 13CO2 production from ingested L-[1-13C]leucine, exercise causes a substantial rise in amino acid catabolism. 3. Amino acids catabolized during exercise appear to become available through a fall in whole-body protein synthesis and a rise in whole-body protein breakdown. After exercise, protein balance becomes positive through a rise in the rate of whole-body synthesis in excess of breakdown. 4. Studies of free 3-methylhistidine in muscle, plasma and urine samples suggest that exercise decreases the fractional rate of myofibrillar protein breakdown, in contrast with the apparent rise in whole-body breakdown.

Adult↗

Zinc absorption in the rat.

1. A method of studying zinc absorption in rats has been developed in which binding of radioactive Zn to the intestinal mucosa and absorption into the carcass was determined at different times after administration by stomach tube. 2. This technique has been used to evaluate different hypotheses concerning the control of Zn absorption and to examine the processes by which this occurs. 3. The proportion of radioactive Zn absorbed into the carcass was found to be dependent on the Zn status of the animals but that found within the small intestinal wall was independent of this, indicating the existence of two mechanisms of Zn absorption. 4. One of these two mechanisms has been shown to be induced by a low dietary Zn content while the other was shown to be insensitive to this. This latter mechanism predominated in rats of normal dietary Zn, status and a study of the characteristics of this process indicated that the quantity of Zn absorbed was proportional to the dietary Zn content over the normal range of intake. This implies that normally Zn homeostasis in rats is achieved through variations in Zn excretion. The additional mechanism of Zn absorption only becomes fully active at levels of dietary Zn below 0.24 MUMOL/g diet.

Animals↗

Contractile properties and fatigue of the diaphragm in man.

We studied the pressure developed by the diaphragm in response to stimulation of the phrenic nerve in the neck, in three normal men. When the phrenic was electrically stimulated at increasing frequencies the diaphragm responded by increasing transdiaphragmatic pressure to give a frequency-pressure curve similar to the frequency-force curve for other skeletal muscles. The subjects than breathed through an inspiratory resistance for as long as possible and the frequency-pressure curve was repeated. It was found that the diaphragm developed low frequency fatigue, in the same way as previously described for other muscles. We conclude that the diaphragm has contractile properties similar to these of other skeletal muscles. Low frequency fatigue of the diaphragm could contribute to respiratory failure in patients with lung disease.

Adult↗