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Biomedical subjects

R H Edwards

Publications and source records attributed to R H Edwards.

At least 289 records · Page 16Linked to original sources

Zinc homeostasis in man: studies using a new stable isotope-dilution technique.

A new method has been developed for the study of zinc metabolism in man using the stable isotope 67Zn. The technique involves intravenous infusion of the isotope followed by measurements of the plasma and faecal enrichments over a period of days. A procedure for the analysis of Zn isotopes in plasma and faeces is described which requires the separation of Zn from other elements using the chelator dithizone before analysis by thermal-ionization mass spectrometry. The stable isotope technique has been used in conjunction with a metabolic balance study to obtain measurements of Zn absorption and gastrointestinal secretion in a normal subject. Preliminary measurements of the size of the exchangeable pool of Zn have been made as have estimates of the rates of plasma and whole-body Zn turnover. Following an increase in dietary Zn the body appeared to respond in two ways. The gastrointestinal secretion of Zn increased immediately, but only by a relatively small amount. The absorption of Zn initially increased in proportion to the increase in dietary levels but then decreased within 4 d by an amount sufficient to restore Zn balance.

Adult↗

Effect of nutrition on vitamin D status: studies on healthy and poorly nourished Brazilian children.

A cross-sectional study was carried out of 412 healthy and 226 chronically malnourished children in Recife, Brazil. Anthropometric measurements, x-rays of hands and wrists, and biochemical data related to skeletal growth were obtained. Levels of plasma 25 hydroxyvitamin D were measured in both groups of children and both showed higher concentrations than those reported for normal European children. The high levels of 25 hydroxyvitamin D found in these two groups of Brazilian children are probably the result of the intense solar radiation in this part of Brazil and argue against the diet being an important source of vitamin D in poorly nourished children. Some bone abnormalities were seen in the underprivileged group of children but in view of our findings these were more likely to be a result of protein-energy malnutrition than rickets.

25-Hydroxyvitamin D 2↗

Experimental skeletal muscle damage: the nature of the calcium-activated degenerative processes.

The role of calcium-activated degenerative processes in the efflux of enzyme from experimentally damaged mouse muscle has been studied using an isolated mouse soleus muscle preparation. Inhibition of mitochondrial activity with dinitrophenol or sodium cyanide was found to cause a large efflux of enzyme. This was largely prevented by withdrawal of the extracellular calcium suggesting that mitochondrial calcium overload does not play a major role in the damage leading to enzyme efflux. Treatment of the muscles with a variety of protease inhibitors had no effect on the enzyme efflux from muscles following exhaustive contractile activity indicating that activation of protease activity is not a major factor in the damaging process. Certain inhibitors of phospholipase-A activity (i.e. dibucaine, chlorpromazine and mepacrine) have been found to significantly reduce the enzyme efflux following treatment of the muscles with dinitrophenol, although other phospholipase inhibitors were without effect. It is suggested that the changes in muscle membrane permeability leading to enzyme efflux following experimental muscle damage are probably the result of calcium-mediated activation of phospholipase A leading to changes in membrane phospholipid metabolism.

Animals↗

Weight reduction in boys with muscular dystrophy.

Many children with muscular dystrophy are overweight, and although weight control is pursued in some centres it is unusual to encourage severe dietary restriction for fear that it might lead to accelerated loss of muscle. In this study, two overweight boys with muscular dystrophy were monitored by whole-body nitrogen balance, total body potassium, strength and functional measurements during calorie restriction. Both patients were found to have a transient loss of nitrogen on commencing the low calorie intake: thereafter, weight loss was not found to have any deleterious effect on muscle bulk or function in either patient. It is suggested that controlled weight-reduction in obese children with muscular dystrophy is a safe and practical way of losing excess fat, which can improve mobility and self-esteem, and may possibly effect longevity.

Adolescent↗

The neuromuscular features of acromegaly: a clinical and pathological study.

A study of the neuromuscular features of acromegaly was performed in six patients. Clinical assessment was supplemented by quadriceps force measurements, plasma creatine kinase (CK) activities, electromyography (EMG) and nerve conduction studies. Muscle mass was measured by urinary creatinine/height indices (CHI) and cross sectional area (CSA) of thighs and calves on computed tomography. Quadriceps force/unit cross sectional area was derived. Needle biopsies of vastus lateralis were studied by histochemical and ultrastructural methods. Mean fibre area (MFA) and fibre type proportions were measured. Most of the subjects studied had muscle pain and proximal muscle weakness confirmed by quadriceps force measurements. This occurred in the absence of muscle wasting, as shown by cross sectional area measurements and normal or raised creatinine/height indices. "Myopathic" features were demonstrated by needle biopsy in half the patients and occasionally by electromyography and raised plasma creatine kinase activity. Abnormalities on needle biopsy included variation in fibre size, type 2 fibre atrophy and large type 1 MFA relative to type 2 MFA. Electronmicroscopy showed the non-specific findings of increased glycogen accumulation, excess lipofuscin pigment and myofilament loss.

Acromegaly↗

Predicted normal values for maximal respiratory pressures in caucasian adults and children.

Maximal respiratory pressures at the mouth (PEmax and PImax) have been measured in 370 normal caucasian children and adults. Age, height, and weight were recorded for all subjects and incorporated in a stepwise multiple regression analysis to determine prediction equations for the maximal respiratory pressures in the children and adults for both sexes. In men PImax and PEmax were significantly correlated only with age (p less than 0.001 and less than 0.035 respectively), whereas in women they were correlated with height (p less than 0.035 and less than 0.03). In both boys and girls PImax was related to weight (p less than 0.0001 and less than 0.01 respectively) and PEmax to age (p less than 0.001 for both). The values for PImax and PEmax in adults were lower than in previously reported series, but in children the values obtained were similar to those reported for several smaller series.

Adolescent↗

Carbonic anhydrase III in Duchenne muscular dystrophy.

Plasma carbonic anhydrase III (CAIII) levels determined by radioimmunoassay have been compared, in detail, with creatine kinase (CK) as indices of Duchenne muscular dystrophy (DMD). CAIII levels were markedly elevated in all patients but variability of levels in a number of individual patients was higher than CK.

Adolescent↗

Vitamin E and skeletal muscle.

Vitamin E deficiency causes a myopathy in a number of animal species but the mechanism of the damage is obscure. The role of vitamin E in protecting skeletal muscle against exercise-induced damage has been investigated using both in situ and in vitro preparations. Muscles from vitamin E-deficient mice and rats were more prone than normal to damage during contractile activity; the tissue rather than the plasma level of the vitamin is probably the more important factor in this respect. Although vitamin E-deficient muscle was found to be more susceptible to peroxidative damage when stressed with iron and ascorbic acid, it was not possible to demonstrate that the damage occurring during contractile activity was mediated by free radicals.

Animals↗

Large delayed plasma creatine kinase changes after stepping exercise.

Muscle changes have been examined in 16 normal subjects (eight female) after both a 20-minute and a prolonged step test. Stepping differs from most exercise tests in that it involves eccentric contractions (negative work) in which the active muscle is lengthened. Plasma creatine kinase (CK), muscle force, contractile properties, and tenderness in the quadriceps were measured for up to 9 days after the exercise. Muscle tenderness was experienced only in the muscles that had performed eccentric contractions (i.e., stepped down). All subjects showed some early rise in CK (less than 400 IU/liter) but eight (both male and female) showed a much greater response (up to 34,500 IU/liter) which took a long time to reach peak levels (4-5 days after stepping). It is suggested that eccentric contractions involved in this form of exercise result in some particular form of muscle damage which, in susceptible subjects, may initiate changes giving rise to a large delayed release of muscle enzymes.

Adult↗

Lipid peroxidation of skeletal muscle: an in vitro study.

The process of lipid peroxidation of skeletal muscle has been examined in vitro by monitoring the autoxidation of skeletal-muscle homogenates. Skeletal-muscle tissue has been shown to have considerable capacity for autoxidation and the process has been found to be initiated by a free-radical-mediated mechanism, critically dependent on the presence of free iron in the homogenate. The initiating radicals have not been firmly identified, but the results suggest that neither superoxide or hydroxyl radicals are involved. An in vitro technique for assessment of the antioxidant capacity of muscle tissue has also been developed which is capable of demonstrating differences between muscle tissues with differing vitamin E contents.

Animals↗

Ultrastructural changes after concentric and eccentric contractions of human muscle.

Four normal subjects performed a 20 min step test using a step of the same relative height. During the test the quadriceps muscle of one leg contracted concentrically throughout by stepping up, while the contralateral muscle contracted eccentrically by controlling the step down. Thus both muscles performed the same amount of work. Three subjects had bilateral needle biopsies just prior to exercise. All four had bilateral biopsies immediately after exercise, and 24-48 hours later when the muscles which had contracted eccentrically were painful. The samples were examined by light and electron microscopy. No abnormalities were seen in pre-exercise samples nor after exercise in muscles which had contracted concentrically. The muscles which had contracted eccentrically showed some damage immediately after exercise. In the samples taken 24-48 hours after exercise the damage was more marked and involved a greater percentage of fibres. In view of the known differences between these types of contractions it is suggested that the initial damage is mechanically induced. The exacerbation of damage with time could be due to mechanical or chemical factors.

Adult↗

Size and composition of the calf and quadriceps muscles in Duchenne muscular dystrophy. A tomographic and histochemical study.

Calf and quadriceps muscle size and composition have been examined in 5 control subjects and 12 boys (aged 7-18 years) with Duchenne muscular dystrophy using computed tomography (CT) and quantitative histochemistry of needle biopsy samples of muscle. In assessing the size of leg muscles it was found that in control subjects the muscle cross-sectional area was related to the cross-sectional area of the femur. The calf muscles in the patients were enlarged both relative to the quadriceps and absolutely when related to the cross-sectional area of the femur used as an index of stature. The enlargement of the calf was the result of accumulations of fat and connective tissue in the presence of relatively normal (compared to femur size) amounts of muscle tissue. Although hypertrophied muscle fibres were a feature of the biopsy samples in the calf the extent of this was insufficient to contribute appreciably to the total muscle enlargement.

Adolescent↗

Investigative strategies for muscle pain.

Muscle pain is the presenting symptom in patients with a wide variety of conditions. Such patients often pose problems in diagnosis and management and a rational scheme for their investigation is needed. The results of muscle biopsy, electromyography, exercise and strength testing and blood measurements in 109 consecutive patients presenting with myalgia are reported. By determining the sensitivity and specificity of the tests in identifying patients with specific muscle abnormalities, a rational investigative protocol has been constructed. Creatine kinase and erythrocyte sedimentation rate are the most useful screening tests and if either is abnormal, muscle biopsy, electromyography, muscle strength and exercise testing are then performed. Despite exhaustive investigation, specific muscle abnormalities were found in only one-third of the patients; whilst many of the remaining patients undoubtedly had a psychogenic component to their pain, it is likely that a number of unidentified specific metabolic defects remain as causes of myalgia.

Adolescent↗

Pain and fatigue after concentric and eccentric muscle contractions.

1. Normal subjects performed a step test in which the quadriceps of one leg contracted concentrically while the contralateral muscle contracted eccentrically. 2. Maximal voluntary force and the force: frequency relationship were altered bilaterally as a result of the exercise, the changes being greater in the muscle which had contracted eccentrically. Recovery occurred over 24 h. 3. Electromyographic studies using three sites on each muscle showed an increase in electrical activation during the exercise only in the muscle which was contracting eccentrically. Recovery followed a time course similar to that of the contractile properties. 4. Pain and tenderness developed only in the muscle which had contracted eccentrically. Pain was first noted approximately 8 h after exercise and was maximal at approximately 48 h after exercise, at which time force generation and electrical activation had returned to pre-exercise values. 5. Eccentric contractions cause more profound changes in some aspects of muscle function than concentric contractions. These changes cannot be explained in simple metabolic terms, and it is suggested that they are the result of mechanical trauma caused by the high tension generated in relatively few active fibres during eccentric contractions.

Adult↗