Hormonal factors in the development of differences in strength between boys and girls during adolescence: a longitudinal study.

The development of elbow flexor (biceps) and knee extensor (quadriceps) strength has been followed in a mixed longitudinal study of 50 boys and 50 girls from the age of 8 to 17 years. Sex differences in strength emerged at the time of peak height velocity and were especially marked for the biceps. Data for individual children were aligned to the time of peak height velocity and associations between strength, height, weight and circulating testosterone were investigated using multi-level modelling. The results show that, for girls, quadriceps strength is proportional to height and weight while for boys there is an additional factor which can be fully attributed to increasing levels of testosterone. Testosterone is important in explaining differences in biceps strength between the sexes but an additional factor is also required. It is suggested that, in addition to a direct effect on muscle, testosterone could have a second indirect action on biceps strength by promoting growth in length of the humerus as part of the general development of the male upper limb girdle.

Modeling developmental changes in strength and aerobic power in children.

The present study examined two contrasting multilevel model structures to describe the developmental (longitudinal) changes in strength and aerobic power in children: 1) an additive polynomial structure and 2) a multiplicative structure with allometric body size components. On the basis of the maximum log-likelihood criterion, the multiplicative "allometric" model was shown to be superior to the additive polynomial model when fitted to the data from two published longitudinal studies and to provide more plausible solutions within and beyond the range of observations. The multilevel regression analysis of study 1 confirmed that aerobic power develops approximately in proportion to body mass, m1/3. The analyses from study 2 identified a significant increase in quadriceps and biceps strength, in proportion to body size, plus an additional contribution from age, centered at about peak height velocity (PHV). The positive "age" term for boys suggested that at PHV the boys were becoming stronger in the quadriceps and biceps in relation to their body size. In contrast, the girls' age term was either negligible (quadriceps) or negative (biceps), indicating that at PHV the girls' strength was developing in proportion to or, in the case of the biceps, was becoming weaker in relation to their body size.

Anaerobic energy production in human skeletal muscle in intense contraction: a comparison of 31P magnetic resonance spectroscopy and biochemical techniques.

Five subjects underwent twenty electrically evoked maximal isometric contractions of the anterior tibialis muscle of both legs (n = 10), with limb blood flow occluded. Measurements of muscle high-energy phosphates (ATP, ADP and phosphocreatine (PCr)), lactate and pH were made using both 31P magnetic resonance spectroscopy (MRS) and the biochemical analysis of biopsy samples obtained from directly below the MRS surface coil. The resting PCr concentration determined using MRS was similar to that measured in the biopsy material. Following contraction, MRS showed a greater decrease in ATP concentration compared with biochemical analysis (P < 0.05), but the decrease in PCr was similar. Good agreement was found when comparing resting muscle pH estimated by the two methods. Post-exercise muscle pH was, however, consistently lower with MRS and consequently the accumulation of muscle lactate estimated using MRS was markedly greater than the corresponding biochemical measurement (P < 0.05). As a result, MRS revealed an approximately 30% greater anaerobic ATP turnover during contraction, although this just failed to reach statistical significance (P > 0.05). The results of the present study indicate that there is little difference in the muscle concentration of PCr estimated by the two methods, but that there are differences in the estimates of ATP, pH and lactate changes during contraction. This latter discrepancy may lead to greater estimates of ATP turnover being made as a result of MRS analysis.

Xanthine oxidase in critically ischaemic and claudicant limbs: profile of activity during early reperfusion.

Xanthine oxidase activity in blood from the ipsilateral femoral vein, and the relationship between xanthine oxidase production and the products of lipid peroxidation, were studied before operation and for 60 min following release of clamps after successful revascularization in two groups of patients with claudication or critical ischaemia. Before revascularization, detectable levels of xanthine oxidase were found only in patients with critical ischaemia. Clamping during bypass surgery led to release of xanthine oxidase in claudicants, but this activity reduced after 60 min. There was no evidence of lipid peroxidation during this time. Xanthine oxidase activity in brachial vein blood was higher than in femoral vein blood in patients with critical ischaemia before revascularization.

Muscle disease, HIV and zidovudine: the spectrum of muscle disease in HIV-infected individuals treated with zidovudine.

Eleven patients with AIDS or AIDS-related complex who developed muscle-related symptoms whilst taking zidovudine were investigated. The clinical details of a further ten patients who did not undergo muscle biopsy are also outlined. The clinical features, quantitative muscle strength testing, electromyographic findings, serial creatine kinase levels, muscle biopsy appearance on light microscopy and the effects of zidovudine withdrawal and rechallenge are described. The spectrum of muscle disease encountered included four cases of frank myopathy diagnosed using clinical, electrophysiological and histological criteria, four patients with mild weakness and myalgia in whom muscle biopsies were normal, three patients with myalgia only and a mild increase in the interstitial cell infiltrate shown by biopsy. The patients presenting with myopathy showed no improvement on withdrawal of zidovudine but responded to immunosuppressive therapy with steroids and, in one case, thalidomide prescribed incidentally. At present, it is not yet possible to clinically define a specific zidovudine-induced myopathy that is distinct from the other effects of HIV infection on muscle structure and function. Our experience suggests that zidovudine may be implicated as a myotoxin in some patients, particularly those with myalgia and mild weakness. In those patients with severe weakness, and with biopsy findings of necrosis and inflammation, the drug effects may be difficult to separate from the primary effects of HIV.

Fibre areas and histochemical fibre types in the quadriceps muscle of paraplegic subjects.

With the advent of functional electrical stimulation (FES) there is the possibility of paraplegic patients regaining some degree of locomotor activity. It is of interest to document the changes in composition histochemistry and size of muscle fibres in such patients both before and after such therapy. We have examined biopsy specimens from quadriceps muscles obtained from 7 male patients, age range 24-47 years, who had been paraplegic for times ranging from 11 months to 9 years and we report the histochemical appearance of the muscle the fibre type composition and the mean fibre areas. In 5 of the 7 subjects there was a marked or complete predominance of fibres which stained as type 2 with the ATPase reaction at pH 9.4. At acid pH these fibres were seen to be predominantly 2B (fast fatigable). The 2 subjects who had been paralysed for the shortest periods had proportions of type 1 fibres which were relatively well preserved. The mean fibre areas of type 2 fibres were below the normal range (2500-7500 microns 2) in every case as were the type 1 fibres in the 4 patients in which these were still present. There was no relationship between the length of time the patient had been paralysed and the mean fibre areas which suggests that atrophy occurs fairly quickly following loss of voluntary control and precedes the loss of type 1 characteristics. Our findings provide an explanation for the rapid onset of fatigue in paraplegic patients taking part in FES programmes since muscles deficient in type 1 fibres will be unable to maintain force for any length of time.

Reperfusion injury in skeletal muscle: a prospective study in patients with acute limb ischaemia and claudicants treated by revascularization.

A study was carried out to document the occurrence of rhabdomyolysis and renal complications in patients undergoing vascular reconstruction. Indices of muscle damage and renal function were monitored before, during and for up to 10 days after vascular reconstruction for a variety of conditions ranging from intermittent claudication to acute ischaemia. Seven patients with acute limb ischaemia (group 1) and nine with intermittent claudication (group 2) were studied prospectively. In group 1, median creatine kinase (CK) and myoglobin levels were markedly raised 24-48 h after surgery (CK, 29,370 units/l; myoglobin, 8.17 mg/l). Myoglobin reached its peak concentration and declined more quickly than CK, but both indices gave similar information about the extent of muscle damage. In contrast, patients undergoing elective surgery for claudication showed no significant departure from reference values for myoglobin or CK. All patients in group 1 underwent fasciotomy to relieve raised compartmental pressures and five were treated with alkali and mannitol to produce diuresis. Despite these measures, two patients suffered renal failure (peak creatinine levels 611 and 590 mumol/l) after successful revascularization and subsequently required haemodialysis; these patients did not have diuresis. One of these patients died following a stroke 8 days after surgery; the other survived and was discharged with a normal limb and restored renal function. There was no evidence of muscle damage or renal complications in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Histology of skeletal muscle in adults with GH deficiency: comparison with normal muscle and response to GH treatment.

The histology of needle biopsy specimens of skeletal muscle from the vastus lateralis was quantitatively assessed in a group of adults with growth hormone (GH) deficiency, most of whom had hypopituitarism treated with conventional pituitary hormone replacement. The mean age of the 21 patients (16 males and 5 females) was 39 +/- 2 (SEM). Comparisons were made with age- and sex-matched controls following six months double-blind, placebo-controlled treatment with recombinant human GH (rhGH) in the GH-deficient patients. Before treatment, needle muscle biopsies from patients with GH deficiency showed mean type I and II fibre areas of 5,153 +/- 273 and 4,828 +/- 312 microns 2 respectively, which did not differ from the controls (4,482 +/- 306 and 4,699 +/- 310 microns 2). Percentages of type I fibres were similar in the two groups (47.2 +/- 2.5% in GH deficiency and 45.3 +/- 2.2% in controls). No difference in the variability of type I or II fibre areas was demonstrated between the groups. Correlations between the relative contribution to total fibre area by type I fibres (mean fibre area x percent) and maximal oxygen uptake (p = 0.006), and between type II fibres and quadriceps force (p = 0.035) were noted in GH-deficient adults before treatment. Following rhGH treatment, no change was noted in mean fibre areas, variability of fibre areas, or percentage of either fibre type.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in skeletal muscle and body composition after discontinuation of growth hormone treatment in growth hormone deficient young adults.

OBJECTIVES: The aim of this study was to determine whether there are any changes in skeletal muscle strength and size and body composition following growth hormone (GH) withdrawal in GH deficient young adults. DESIGN: A longitudinal, 1-year, open, uncontrolled study of the changes in skeletal muscle and body composition following GH withdrawal was performed. Endocrine status was reassessed at the end of the study period during an insulin tolerance test. Some measurements were repeated after 2 years of treatment. PATIENTS: Twelve (11 male, one female; age range 14-21) patients who had been diagnosed during childhood as growth hormone deficient took part in the study. Four of the 12 patients were found to have a normal GH response on retesting at the end of the study and their results were analysed as a separate group. MEASUREMENTS: Quadriceps and forearm flexor maximum voluntary isometric strength, body fat content and serum IGF-1 were measured at 3-monthly intervals over 1 year. Every 6 months muscle size was measured from computerized tomography scans and fibre area from quadriceps needle biopsy samples. RESULTS: For the growth hormone deficient group the 12 month quadriceps strength, size and fibre areas were 94.0% +/- 8.5 (mean +/- SD), 94.5% +/- 6.3 and 85.6% +/- 17.7 respectively of control (baseline) values. Forearm flexor strength and size were 101.4% +/- 7.9 and 92.0% +/- 9.2 of control. Body fat percentage had increased from 19.5% +/- 8.6 to 24.1% +/- 9.5. No change was seen in the non-growth hormone deficient group. CONCLUSIONS: Although the changes measured were relatively small they suggest a role for GH in the maintenance of muscle integrity and body composition in the young adult with growth hormone deficiency.

Assessment of the effect of oral corticosteroids on bone mineral density in systemic lupus erythematosus: a preliminary study with dual energy x ray absorptiometry.

Dual energy x ray absorptiometry and a wide range of blood and urine tests were used to assess the propensity of patients with systemic lupus erythematosus to develop an impairment of bone mineral density. Surprisingly, in this preliminary study no significant differences in bone mineral density were found when patients taking 10 mg or more of prednisolone for six months or longer were compared with those who had never taken prednisolone.

A cross-sectional survey of upper and lower limb strength in boys and girls during childhood and adolescence.

Changes in height and weight during childhood and adolescence are well documented, yet there is comparatively little comprehensive information about muscular development during this time. In a cross-sectional survey standing height, body weight and isometric strength of the elbow flexor and quadriceps muscles have been measured in 267 boys and 284 girls aged from 5 to 17 years. All the children were from private London schools. The mean heights and weights for each age group were between the 50th and 75th centiles for British children. The strength of both muscle groups in the boys and girls rose steadily in each age group from 8 to 12 years, after which there was a rapid increase in strength of both the quadriceps and elbow flexors in boys which continued even when growth in height and body weight had virtually ceased. In the pre-adolescent phase of growth, muscle strength of the elbow flexors and quadriceps increased as a function of height squared and cubed respectively, suggesting that stretch as a result of elongation of the long bones, and for the quadriceps, loading, may be the primary stimuli during this phase. In the postpubertal phase some other stimulus, such as a direct action of hormones on the muscle, must be responsible for the continued increase in strength in the boys.

Muscle fibre type and aetiology of obesity.

Proportions of slow (type 1) muscle fibres of the vastus lateralis and percentage body fat were measured in 11 healthy sedentary men. The proportion of slow muscle fibres was inversely related to fatness; at least 40% of the variability in fatness may be related to variation in muscle fibre type. Metabolic evidence in 50 men, provided by the respiratory exchange ratio (RER) during cycle ergometry, indicated that fatter men (or, in the subset of 11 men, those with a low proportion of slow muscle fibres) combusted less fat during work at 100 W than did lean men (or those with a high proportion of slow fibres). The effects of fitness and of body size were excluded in the analysis. The evidence supports the hypothesis that muscle fibre type is an aetiological factor for obesity.

Long-lasting unilateral muscle wasting and weakness following injury and immobilisation.

Quadriceps strength and size was measured in a small group of subjects (n = 7) 1 to 5 years after full mobilisation following some form of unilateral lower limb trauma. The mean maximum voluntary isometric force (MVC) was significantly lower for the injured (I) compared to the uninjured (UI) leg (369 N +/- 139 vs. 535 N +/- 131, p less than 0.01). Electrical stimulation superimposed on the voluntary contractions demonstrated that all subjects were able to maximally activate the quadriceps of both legs. Mean quadriceps cross-sectional area (CSA) was significantly lower in the I (64 cm2 +/- 12.8) compared to the UI leg (80 +/- 12.8, p less than 0.01). One subject with marked unilateral weakness and wasting took part in a 3-month strength training study for the injured leg. After training the I/UI ratio had been restored to nearly 100% (94% MVC; 88% CSA). These results would suggest that longer and more intensive physiotherapy is required in the immediate post-injury period to restore muscle strength and size to severely atrophied muscle.

Injury to skeletal muscles of mice by forced lengthening during contractions.

Our purpose was to determine the amount of injury to extensor digitorum longus (EDL) and anterior tibial (ATB) muscles of mice from 1 h to 30 days following passive shortening and lengthening, shortening contractions and lengthening contractions. The shortening-lengthening cycle was of 600 ms duration and was repeated every 5 s for 30 min. Contractions were produced during either the shortening or lengthening phase with stimulation at 100 Hz for 300 ms. The amount of injury was evaluated by the decrease in the number of fibres in a cross-section of the muscle and in the maximum isometric tetanic force (Po). Passively shortened and lengthened and actively shortened EDL and ATB muscles showed no evidence of injury. At 3-5 days after lengthening contractions, EDL and ATB muscles showed an inflammatory response. At 3-5 days, the number of fibres in the cross-section of the injured EDL muscles was 65% of that of the contralateral control EDL muscle, whereas no change was observed in the number of fibres in the injured ATB muscles. By 3 days, the presence of myoblasts, myotubes and central nuclei indicated regeneration of fibres. One hour after shortening contractions, the Po of EDL and ATB muscles decreased to about 75% of the contralateral control value, but recovered completely by 3 days. In contrast, 1 h after lengthening contractions the Po of EDL and ATB muscles decreased to 52 and 40% respectively of the contralateral control value and then both recovered to about 65% within 3 h. For the ATB muscle, the Po showed a secondary decrease to 49% of the contralateral control value at 1 day and for the EDL muscle, to 47% at 3 days. Each muscle recovered gradually and by 30 days the number of fibres and the Po of the injured muscles were not significantly different from values for contralateral control muscles.

Changes in skeletal muscle after discontinuation of growth hormone treatment in young adults with hypopituitarism.

Skeletal muscle strength and size were measured for 1 year following discontinuation of human growth hormone (hGH) treatment in 11 patients with hypopituitarism. Quadriceps and forearm flexor maximum voluntary isometric strength and size were measured. At the end of the study, endocrine status was reassessed by an insulin tolerance test. Three of the 11 subjects were found to have normal hGH secretion and were not included in the analysis. At 12 months, quadriceps strength, size and fibre areas were 94.0 +/- 8.5%, 94.5 +/- 6.3% and 85.6 +/- 17.7% (mean +/- SD), respectively, of baseline values. Forearm flexor strength and size were 101.4 +/- 7.9% and 92 +/- 9.2% of control values. Although these changes are relatively small, they suggest a role for growth hormone in the maintenance of muscle in the adult.

Abnormalities of skeletal muscle in patients with chronic heart failure.

We have examined muscle strength, mitochondrial enzyme activity, histochemistry and fibre size in the quadriceps muscle of 9 patients with severe chronic heart failure. A needle biopsy of the quadriceps muscle was taken with patients at rest. Maximum oxygen uptake was measured during treadmill exercise. Mean maximal oxygen consumption was 11.7 ml.kg-1.min-1. Isometric maximum voluntary contraction was reduced to 55% of the predicted value for weight. Eight biopsies were abnormal. Findings included increased acid phosphatase, increased interstitial cellularity, excess intracellular lipid accumulation, atrophy of both type I and II fibres and variation in size with hypertrophy and atrophy of fibers. Muscle fibre capillary density and the activity of mitochondrial enzymes were normal. Changes in skeletal muscle strength may play a role in the limitation of exercise capacity seen in patients with congestive heart failure.

Cellular infiltrates in human skeletal muscle: exercise induced damage as a model for inflammatory muscle disease?

The type and distribution of mononuclear cell infiltrates in muscle biopsies taken from 9 subjects at differing times after exercise in which the muscle is stretched (eccentric exercise) has been characterised. The appearances are compared to those seen in muscle from patients with inflammatory muscle disease. After exercise infiltrating cells were seen in perivascular, perimysial and endomysial regions, the extent being greater in the later biopsies (9-14 days). The predominant cell type was the macrophage (46-100% of all infiltrating cells), the remainder were T lymphocytes with a predominance of the CD4 positive helper/inducer subset. Approximately one third of the T cells expressed DA2 (class 2) antigen indicating that they were activated. Very few B lymphocytes and no Leu7 positive cells were seen. There was evidence of class 1 expression on some of the damaged muscle fibres. The appearance of the experimentally damaged muscle in normal subjects was very similar to untreated polymyositis suggesting that a proportion of the infiltrating cells seen in this disease may be present as part of a natural response to damage rather than being its cause.

An examination of some factors influencing creatine kinase in the blood of patients with muscular dystrophy.

The natural variability of plasma creatine kinase activity has been examined in patients suffering from muscular dystrophy and in normal subjects. The coefficient of variation of the plasma creatine kinase activities was found to be large (approximately 35%) in both patients with Duchenne muscular dystrophy and normal control subjects. A comparison of the plasma activities of creatine kinase with other muscle-derived enzymes suggests that the cause of this variability is changes in the release of enzymes from muscle. Data obtained concerning the effect of physical activity on plasma creatine kinase activity are contradictory, but several young patients with Duchenne muscular dystrophy and a very high creatine kinase activity (greater than 5000 IU/liter) showed a decreased activity following admission to hospital. An estimate of the rate of efflux of certain kinase from muscle has been made, indicating that young ambulant patients with Duchenne muscular dystrophy have a grossly elevated muscle creatine kinase efflux (495.0 +/- 61.3 IU/kg muscle/hr) compared to control subjects (1.4 +/- 0.5 IU/kg muscle/hr).