Biomedical subjects
Publications and source records attributed to R B Fitzsimons.
Kidney length was measured in 115 unselected neonates with portable real-time ultrasound. The left kidney was slightly, but significantly, longer than the right. There was a positive correlation between kidney length and birthweight, but kidney size did not increase significantly after 36 weeks gestation. Further ultrasound studies of the newborn kidney will be of interest.
An analysis of the native myosin isoenzyme composition, myosin light-chain distribution and histochemical profile of fast-twitch and slow-twitch muscles of normal and dystrophic (129 REJ dy/dy) mice has been performed, and the results correlated with the known contractile abnormalities of murine dystrophic muscles. Normal mouse slow-twitch soleus contained two isomyosins (slow myosin, SM and intermediate myosin, IM) which were electrophoretically distinct from the three major isomyosins (FM1, FM2, FM3) of fast-twitch extensor digitorum longus (e.d.l.) muscle. The calcium-activated ATPase activities of FM1, FM2, FM3 and IM at pH 9.2 were each much higher than that of SM, and this difference is reflected in the histochemical profile of muscle, as demonstrated with the myofibrillar ATPase reaction at alkaline pH. E.d.l. Type II fibres retained myofibrillar ATPase activity following pre-incubation of histochemical sections at pH 4.6, and were therefore classified Type IIB, whereas soleus Type II fibres did not, and were classified Type IIA. It was concluded that Type I (slow) fibres contain SM, Type IIA (intermediate) fibres contain IM, and Type IIB (fast) fibres contain FM1-FM3. Each electrophoretically distinct myosin contained a different combination of the five skeletal myosin light chains (LCs). Thus different normal muscles, which differed in their isomyosin profiles, differed also in their light-chain composition. Analysis of the distribution of native myosins (FM1, FM2, FM3, IM, SM, in order of decreasing gel migration rate) in dystrophic muscles revealed increased proportions of the slower-migrating forms, when compared with the distribution in the corresponding normal muscles. The shift in isomyosin distribution would explain the known decrease in the proportion of myosin light chain (LCf3) in murine dystrophic muscle. The abnormal isomyosin distribution in the dystrophic muscle is correlated with its altered histochemical characteristics, and with well-established abnormalities in its isometric and isotonic properties. It is concluded that the altered isomyosin distribution in murine dystrophic muscle would result in decreased power output per unit muscle mass when compared with normal muscle. The possibility is considered that defective myelination of the innervating nerve may contribute to these abnormalities by preventing higher frequency impulses from reaching muscle.
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Two adult patients are described with long-standing primary myopathy characterised on light microscopy of skeletal muscle biopsy by central nuclei within muscle fibres, and on electron microscopy by multiple minicores causing sarcomere disruption. The total pathological picture is not typical of either "centro-nuclear myopathy" or "multicore disease". The apparently benign long-term prognosis of the myopathy in these patients contrasts with the severe respiratory dysfunction described in two recently reported infants affected by a pathologically similar myopathy, and justifies extensive respiratory support measures in such cases. In both cases electrophoresis of native myosin revealed only the "slow" isoenzymic forms. This finding is consistent with the overwhelming predominance of Type I fibres in the muscle biopsy. No foetal myosins, which characterize developing or regenerating muscle, were detected.
Human myosin from different skeletal muscles was analysed in a non-denaturing gel system, and the isoenzyme composition correlated with the histochemical composition of the muscle. Two components (SM1 and SM2) were associated with type 1 (slow-twitch) fibres, and three (FM1, FM2 and FM3) with type 2 (fast-twitch) fibres. Light-chain analysis was performed in sodium dodecyl sulphate/polyacrylamide gels. There are three light chains (LCs1a, LCS1b and LCs2) in type 1 fibres, and three (LCf1, LCf2 and LCf3) in type 2 fibres. LCf1 and LCs1b co-migrate in sodium dodecyl sulphate gels. The ratio of LCf3/LCf2 is correlated with the distribution of the individual fast isoenzymes. These results explain apparent discrepancies in the literature concerning the light-chain distribution of human myosin.
Two infants with congenital skin defects were born to mothers who had uneventful pregnancies; drugs were not ingested, nor was any infection noted. Maternal plasma zinc and copper were measured postnatally and were found to be abnormal. We suggest that these skin abnormalities were related to maternal zinc deficiency.
A case of mitochondrial myopathy and lactic acidaemia with myoclonic epilepsy, cerebellar ataxia and high-tone hearing loss is presented. There was no ptosis or ophthalmoplegia. Endocrine investigations showed a defect in hypothalamic function which was a likely cause of infertility. The case is compared with previously reported examples of mitochondrial myopathy with myoclonic epilepsy, and contrasted with the Kearns-Sayre syndrome. It is concluded that mitochondrial myopathy, myoclonic epilepsy and ataxia may be distinguishing features of a specific familial disease, which on presentation may mimic the Ramsay-Hung syndrome.
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Nine cases of mitochondrial myopathy are presented and the literature is reviewed. The clinical picture ranges from virtually pure ophthalmoplegia, through 'ophthalmoplegia plus' to predominantly central nervous system disturbance. Morphological mitochondrial abnormalities are likely to reflect generalised metabolic abnormalities of diverse aetiology, but producing common pathophysiological consequences. The association of mitochondrial myopathy with CNS disorders, which may ante-date muscle weakness, is emphasised. The myopathies constitute a clinical continuum within which the following syndromes may be delineated: (1) Kearns-Sayre syndrome (2) Luft's disease (3) a variant of Ramsay Hunt syndrome (4) relapsing febrile neurological deficits with headache and seizures. These may be specific diseases or artificially separated manifestations of some common metabolic disorder(s). There is a similarity between the CNS pathology, and also some clinical features, of Leigh's disease and the findings in certain of the mitochondrial myopathies. The review suggests that the following should be regarded as associations of mitochondrial myopathy and progressive external ophthalmoplegia (a) diabetes mellitus (b) cataracts, in which calcium deposits may, like basal ganglia calcification, be due to abnormal calcium metabolism. Diplopia, although unusual, does occur in progressive external ophthalmoplegia with mitochondrial myopathy.
Seven cases from a family with a myopathy categorized as "multicore disease" are presented. The clinical picture is unusual because of the predominant progressive involvement of the axial skeletal muscle, with scoliosis and disproportionate respiratory failure as the major clinical features. The propositus and his cousin have both suffered from scoliosis without limb weakness. There is a possibility that this myopathy may be responsible for some cases regarded as idiopathic scoliosis, especially idiopathic infantile scoliosis. The clinical picture is highly variable, and there are sub-clinical cases. The inheritance pattern is consistent with either autosomal dominant, sex-linked recessive or extra-chromosomally inherited disease. Electron microscopy revealed mitochondrial abnormalities, which may have resulted in the Z-disc pathology.
Presumptive embolic chorioretinal Torulopsis glabrata infection is described in a patient who had received prolonged intravenous antibiotic therapy. The ocular findings are compared and contrasted with embolic lesions due to Candida albicans. The patient was treated for 6 weeks with intravenous miconazole. During this time there was shrinkage of the ocular lesions, some improvement in vision and abolition of fungaemia. Improvement in tests of immune function during treatment suggests that an early immunological deficit was secondary to the infection. Intravenous miconazole is a relatively nontoxic alternative to amphotericin and deserves further evaluation in the treatment of ocular mycosis.
2 cases of back curvature considered to be due to myopathy, but without associated limb weakness, are described. 1 case presented as infantile kyphosis with subsequent progression to scoliosis. There were some associated myopathic clinical features, including recurrent herniae and hip and knee contractures. The second case presented as an otherwise classical instance of Scheurmann's disease. Paraspinal muscle in both cases showed nonspecific abnormalities consistent with varieties of minimal change myopathy. EMG examination of limb muscles revealed myopathic abnormalities. These cases support the hypothesis that myopathy may underly some cases of apparently idiopathic scoliosis or kyphosis.
Electrophoresis of intact myosin ATPases extracted from fast-twitch and slow-twitch muscles of dystrophic mice, and from control mice, was performed. The proportions of the lower ATPase myosin were increased in the dystrophic muscles. These results correlated with the abnormalities in the isometric myogram and the force/velocity relationships which have been described.
Recently described techniques for separating myosin isoenzymes have been adapted for analysis of myosins from diseased and developing human skeletal muscle. The method is highly suitable for analysis of human myosins because only 2 - 3 mg of muscle are required for routine analyses. Human embryonic/foetal myosins are electrophoretically distinct from mature skeletal myosins, and are not normally detected beyond the first month of post-natal life, except in premature infants. They have a high alkaline calcium-activated ATPase activity. This would account for the histochemical classification of foetal fibres as "Type II", although physiological differences between adult fast-twitch muscle and foetal muscle are well recognized. Foetal myosins are also synthesized in human skeletal muscle under certain pathological circumstances. Their presence in Duchenne dystrophy probably reflects the associated marked muscle regeneration, with immaturity of some muscle cells. The large amounts of foetal myosin present in many cases of infantile spinal muscular atrophy is evidence that innervation is necessary for the normal cessation of foetal myosin synthesis.