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Biomedical subjects

R H Edwards

Publications and source records attributed to R H Edwards.

At least 361 records · Page 20Linked to original sources

Weakness in myotonic syndromes.

Muscle weakness occurs in a number of myotonic syndromes, including those in which muscle bulk is preserved. The possible causes of muscle weakness may be considered in terms of the different stages of the electromechanical activation process and defects in the contractile machinery. In individual myotonic disorders the ability to identify the origin of the muscle weakness (whether neurogenic or myogenic) and the functional level at which the defect occurs would assist the choice of rational treatment.

Action Potentials↗

Human skeletal muscle function: description of tests and normal values.

1. The force produced by isometric contractions of the quadriceps muscle have been studied during maximal voluntary contractions and when a substantial part of the muscle was electrically stimulated via surface electrodes. 2. In normal children and adults, the force of a maximal voluntary contraction of the quadriceps was proportional to body weight. 3. The function of the quadriceps has been described in terms of the force/frequency curve, speed of relaxation and the rate of loss of force during 18 s stimulation at 30 Hz and 100 Hz. 4. The functional characteristics of adductor pollicis when stimulated via the ulnar nerve were essentially similar to those of the quadriceps. 5. Studies of the function of these two muscles are complementary since quadriceps femoris is amenable to needle biopsy investigations of its structure and chemistry whereas adductor pollicis is more suitable for electrophysiological studies.

Adolescent↗

A study of the contractility, biochemistry and morphology of an isolated preparation of human skeletal muscle.

1. A new method of studying isolated human skeletal muscle has been evaluated. This involves the incubation and electrical stimulation of strips of muscle, obtained at surgical biopsy, that are tied at the cut ends of the fibre bundles. 2. Morphological examination showed that the fibres were sealed off at the cut ends. Damage appeared to be restricted to the areas immediately adjacent to the ties. 3. Contractile properties were well maintained for several hours and measurements of tissue metabolites showed that muscle contents of the high-energy phosphate compounds were well preserved. 4. The isolated preparations were found to have the same contractile properties as human quadriceps femoris studied in vivo by the methods described in the preceeding paper. 5. Correlation was found between the relaxation speed of the isolated preparations and their fibre-type composition histochemically determined. 6. It is concluded that this technique is a valid addition to the present methods of studying the physiology and pharmacology of human skeletal muscle.

Adenosine Triphosphate↗

Functional and structural changes after disuse of human muscle.

1. Seven patients who had suffered unilateral leg fracture were studied after removal of immobilizing plaster casts. 2. Leg volume measured anthropometrically was reduced by 12% in the injured leg (5-68 +/- 1-05 litres) compared with the uninjured (6-43 +/- 0-87 litres). Associated with this loss was a similar reduction in the net maximum oxygen uptake achieved in one-leg cycling, from 1-89 +/- 0-21 1/min in the uninjured leg to 1-57 +/- 0-18 1/min in the injured. 3. Measured by a percutaneous needle biopsy technique, a reduction of 42% was found in the cross-sectional area of the muscle fibres sampled from the vastus lateralis of the injured compared with the uninjured leg. 4. Staining for myosin adenosine triphosphatase activity showed that both type I and II fibres were affected, being reduced respectively from 3410 to 1840 micronm2 and from 3810 to 2390 micronm2 cross-sectional area. 5. Possible reasons and implications are discussed for the discrepancy between the magnitude of the difference observed in the gross measurement of leg function (maximum oxygen uptake) and structure (leg volume) as compared with the cellular level (cross-sectional fibre area).

Adolescent↗

Clinical investigations of muscle contractility.

The use of tests of muscle contractility based on electrically stimulated contractions means that information obtained from the more traditional tests of voluntary muscular performance and strength may be complemented by indices which are independent of volition and independent of muscle mass. Such tests are no longer limited to peripheral muscles but may now be applied to a large proximal muscle--the quadriceps femoris. This report describes the in vivo testing of a drug's pharmacological activity on the quadriceps muscle by a study of the relative forces produced by different frequencies of stimulation. It also illustrates that hypothyroidism is not the only endocrine disorder whose treatment may be monitored by measuring the speed of muscle relaxation. Finally, it describes a patient whose quadriceps weakness was explained by the demonstration of the failure of the muscle to maintain tension during prolonged stimulation.

Clinical Trials as Topic↗

1alpha-hydroxyvitamin D3 in the treatment of nutritional and metabolic rickets and osteomalacia.

Five patients with nutritional osteomalacia or rickets and six children with rickets unresponsive to physiological doses of vitamin D were treated with 1alpha-hydroxyvitamin D3 (1alpha-OHD3). Patients with nutritional osteomalacia responded to 1--2 microgram/day of 1alpha-OHD3. The most striking findings were rises in plasma calcium and, in one case, a decrease in faecal calcium. In some cases there was a rise in plasma phosphorus, alkaline phosphatase remained unchanged. There was radiological healing. In three patients with cystinosis and one with hypophosphataemia and Barrter's syndrome 2 microgram of 1alpha-OHD3 produced healing of rickets. Plasma phosphate rose on treatment, possibly by a suppression of parathyroid activity. The response to such low doses of 1alpha-OHD3 suggests impaired 1alpha-hydroxylation of 25-hydroxyvitamin D in these patients. A patient with intestinal malabsorption was resistant to high doses of 1alpha-OHD3 by mouth but responded to parenteral administration. A boy with osteopetrosis and the biochemical changes of rickets was resistant to large doses of 1alpha-OHD3 presumably because of failure of osseous response.

Adolescent↗

Fatigue of long duration in human skeletal muscle after exercise.

1. After severe muscular contraction in man recovery of force is largely complete in a few minutes, but is not wholly so for many hours. The long-lasting element of fatigue is found to occur primarily for low frequencies of stimulation (e.g. 20/sec), and is much less pronounced, or absent, at high frequencies (80/sec). The twitch force is an unreliable measure of the state of fatigue. 2. The long-lasting element of fatigue is not due to depletion of high-energy phosphate nor is it due to failure of electrical activity as recorded from surface electrodes. It is probably the result of an impairment of the process of excitation-contraction coupling. Its practical importance for man could be significant as an explanation of the subjective feelings of weakness following exercise.

Adenosine Triphosphate↗

Exertion of stairclimbing in normal subjects and in patients with chronic obstructive bronchitis.

The exertion of stairclimbing has been studied in 10 normal young men, 10 healthy middle-aged men, and 10 middle-aged men with chronic bronchitis. Subjects climbed a staircase with a total vertical ascent of 40.8 m. They were allowed to adopt the most comfortable pattern of ascent, the patients having to stop at intervales for rest pauses. Work rate was determined by timing the raising body weight over measured sections of the staircase. Perception of exertion estimated with a numerical scale, heart rate, and increase of blood lactate concentration were closely similar in all three groups at the top of the staircase. In the patients, average power output was directly dependent on lung function, as indicated by the forced expired volume in 1 second. Stairclimbing offers a simple way of studying a patient's spontaneous activity pattern in a 'real life' environment. Studies of the kind described here could usefully complement formal exercise testing in the laboratory.

Adult↗

The time course of phosphorylcreatine resynthesis during recovery of the quadriceps muscle in man.

The time course of phosphorylcreatine (PC) resynthesis in the human m. quadriceps femoris was studied during recovery from exhaustive dynamic exercise and from isometric contraction sustained to fatigue. The immediate postexercise muscle PC content after either form of exercise was 15-16% of the resting muscle content. The time course of PC resynthesis during recovery was biphasic exhibiting a fast and slow recovery component. The half-time for the fast component was 21-22s but this accounted for a smaller fraction of the total PC restored during recovery from the isometric contraction than after the dynamic exercise. The half-time for the slow component was in each case more than 170 s. After 2 and 4 min recovery the total amount of PC resynthesized after the isometric exercise were significantly lower than from the dynamic exercise. Occlusion of the circulation of the quadriceps completely abolished the resynthesis of PC. Restoration of resynthesis occurred only after release of occlusion.

Adenosine Triphosphate↗

Measurements of muscle strength and performance in children with normal and diseased muscle.

A study has been made of two simple means of measuring muscle power in children with normal and diseased muscle. In one the length of time that the leg and the head could be held at 45 degrees above the horizontal was measured with the child supine. In the second, measurements were made of the isometric strength of six muscle groups with the newly developed Hammersmith Myometer. In the timed performance tests only 5 (8%) of a group of 61 children known to have muscle disease achieved the minimum expected values for their ages. Myometer readings of the isometric power of the children with muscle disease also have values which were below those of a comparable group of normal children. The reproducibility of muscle strength measurements in young children has been shown to be good, whereas the timed performance tests, though able to differentiate normal children from children with muscle disease, did not show sufficient reporducibility for this test to be recommended for sequential measurements.

Adolescent↗

British pilot study of exercise therapy. I. Middle-aged men.

The physiological and biochemical effects of a carefully graduated course of vigorous gymnasium training with two or three weekly exercise sessions lasting only 15 minutes have been studied in middle-aged London business men. Activity diaries and psychological questionnaires indicated that these men had a positive attitude to exercise which was probably greater than average. The gymnasium exercises caused a large oxygen debt and considerable rises in plasma catecholamines and lactate levels. A close correlation was found between the pulse rate during exercise and the Borg scale of perceived exertion, so that both could be used to ensure that short periods of exercise were sufficiently vigorous to produce a training effect, and protect against over-exertion. The acceptability of this particular exercise regime was shown by the low fall-out and injury rate. It is suggested that this exercise training programme possesses many features which are advantageous if increased physical activity is to be more widely used as a method of reducing some of the risk factors in coronary heart disease.

Adult↗

Needle biopsy for muscle chemistry.

Needle biopsy can readily provide samples of human skeletal muscle for biochemical analysis. Muscle metabolites are measured by enzymic microanalytical techniques and electrolytes by neutron-activation analysis. This paper summarises the methods of analysis, gives the normal ranges for muscle contents of metabolites and electrolytes, and reviews the reported changes in a number of neuromuscular and metabolic disorders. Muscle is a fairly homogeneous tissue in health, but replacement with fat and fibrous tissue in myopathies causes error in analyses unless metabolites are referred to a reliable standard. It is recommended that needle-biopsy samples to be freeze-dried and dissected to remove connective tissue before analysis. Total creatine (phosphorylcreatine+free creatine) total adenosine+inosine nucleotides, and potassium and phosphorus separtely correlated very highly with sample dry weight after dissection, suggesting that these may be used as standards. When assessing whether a given metabolite is present in an abnormal amount, it is probaby advisable to check the content with reference to more than one standard, since one or more of these may be changed in disease.

Adenine Nucleotides↗

Metabolic changes associated with the slowing of relaxation in fatigued mouse muscle.

1. The biochemical basis of the slowing of relaxation seen in fatigue has been examined using an isolated mouse soleus preparation. 2. Slowing of relaxation occurred during prolonged tetani under anaerobic conditions when ATP and PC fell and lactate accumulated. 3. Slowing of relaxation was also demonstrated with muscles poisoned with cyanide and iodoacetic acid when there was a fall in ATP and PC but no accumulation of lactate. During a period of anaerobic recovery following a fatiguing tetanus, relaxation became faster at a time when lactate was accumulating in the muscle. 4. It is concluded that the slowing of relaxation in fatigue is not a consequence of lactate accumulation, and a relationship is demonstrated between the ATP content of the muscle and the rate of relaxation in muscles fatigued by prolonged stimulation, 5. Rates of ATP turn-over in fresh muscle, and at intervals throughout a tetanus are consistent with the suggestion that the rate limiting step for myofibrillar ATPase may be directly related to the rate limiting step for the decay of tension during relaxation.

Adenosine Triphosphate↗

Heat production and chemical changes during isometric contractions of the human quadriceps muscle.

1. Development of a new thermal probe and use in conjunction with chemical analysis of needle biopsy samples, has made possible a thermodynamic study of the energetics of muscular contraction in the human quadriceps. 2. The observed rate of muscle temperature rise was proportional to the force of the contraction. During maximal contractions the rate of heat production was 54 +/-8-5 W/kg wet muscle (mean +/- s.d.). 3. The observed rates of muscle temperature rise agreed well with the rates calculated from the measured metabolite changes when standard values for the enthalpy changes of the reactions involved were used. 4. During prolonged stimulation of the quadriceps at 15/sec via the femoral nerve, the rate of heat production per unit force fell to nearly half the initial value. It is estimated that this represented a two- to fourfold increased in economy of ATP turn-over required to maintain a given force. 5. Relaxation becomes progressively slower during prolonged contractions and it is suggested that the slowing of relaxation and the increased economy of force maintenance may both be due to an increased cross-bridge cycle time in the fatigued muscle.

Adenosine Triphosphate↗

An analysis of the physiological strain of submaximal exercise in patients with chronic obstructive bronchitis.

An increasing work rate was performed by 40 patients with chronic obstructive bronchitis, split into two groups according to FEV1 (group M, mean FEV1 1-451. and group S, mean FEV1 0-621.), and by 20 normal, non-athletic men of similar age to the patients. Values for cardiac frequency and ventilation were interpolated to standard oxygen uptakes of 0-75, 1-0, and, where possible, 1-5 min-1. The tidal volume at a ventilation of 20 and 30 1 min-1 was also determined. The cardiac frequencies at oxygen uptake of 0-75 and 1-01 min-1 were significantly higher in the patient groups than in the normal men, and were highest in patient group S. The cardiac output when related to the oxygen uptake was in the normal range in all three groups of subjects, so that the patients had smaller stroke volumes than the normal men. Ventilation at oxygen uptakes of 0-75 and 1-01 min-1 was significantly higher in both patient groups than in the normal subjects; there were no significant differences between the two patient groups, Values for dead space/tidal volume ration, alveolar-arterial oxygen gradient, and the percent venous admixture measured during a constant work rate test were significantly greater than normal in the patient groups. Possible factors limiting exercise tolerance in these patients were assessed by extending the increasing work rate test from submaximum to maximum exercise. Changes in blood gas tensions and blood lactate concentrations from resting levels were small, and probably did not limit exercise performance. Measurements at maximum exercise did not add appreciably to the analysis of the disturbed cardiopulmonary function. This study has shown that major disturbances in cardiopulmonary function can be demonstrated without the need for stressing a patient to the limit of his effort tolerance.

Aged↗