Australian paediatric journal最新文献

The gene on the X chromosome which, when abnormal, causes Duchenne muscular dystrophy (DMD) is estimated to be at least 1800 kb in length, making it possibly the largest in the entire human genome. Cloned mRNA derived from the gene indicates that it codes for a protein with a molecular weight of approximately 400,000 daltons. This protein, which is expressed in very low concentration (one molecule to each of 15 muscle nuclei), has been named dystrophin. It is anticipated that the molecular biology of dystrophin will now be elucidated quickly so that its function in the cell is revealed and steps to correct the biochemical defect initiated. It is also possible that the gene codes for a family of proteins and that these reside within the intermediate filament system of the cytoskeleton. Candidate proteins are spectrin, nebulin and titin, as well as dystrophin. In the light of these advances in the molecular genetics of DMD, it is timely for the myopathologist to suggest possible mechanisms of aetiopathogenesis for the disorder. In this regard the first unequivocal lesion in muscle biopsies in DMD is focal muscle fibre necrosis. Electron microscopy (EM) reveals excessive hypercontraction of sarcomeres, especially in the early stages. These hypercontracted zones correspond to the 'hyalinized' muscle fibres typical of the disorder. It seems possible that such hypercontractions cause tears in the plasma membrane of the muscle fibre which may be weakened by an abnormality of the intermediate filaments which underlie the lipid bilayer.(ABSTRACT TRUNCATED AT 250 WORDS)

Fasciculations may be generated at any point on a hyperexcitable lower motor neuron. Physiological ('benign') fasciculations often begin suddenly and persist for years without development of muscular wasting or weakness. Fasciculations may be a sign of degeneration of lower motor neurons in which case they may be associated with muscle cramps and neuromyotonia. Both sensory and motor axons are overactive in neuromyotonia, the symptoms of which are relieved by administration of anticonvulsants such as carbamazepine. Spinal muscular atrophy is a feature in some cases of progressive myoclonic epilepsy of the systems degeneration type that may be overlooked because muscular wasting is overshadowed by the dramatic appearance of action myoclonus.

Administration of inhibitors of prostaglandin synthetase to chicken embryos produced myopathies in their skeletal muscles which were characterized by ringbinden, loss of Z-discs, M-bands, and thick and thin filaments and decreased myoblast proliferation and type 2 myotube formation. The effect of administration of prostaglandins on myoblast proliferation was also examined and PGE was found to suppress proliferation. There was also a tendency for PGF2 alpha to suppress and PGI2 to stimulate proliferation, although neither of these effects were statistically significant. PGA, PGB and PGD did not affect myoblast proliferation.

One hundred and twenty-five cases of biopsy-proven subacute or chronic peripheral polyneuropathy occurring in children under 17 years of age are reviewed. Ninety-three (74%) of the cases have been examined by the authors. At least 71% of cases were considered to be of genetic origin. Hereditary motor and sensory neuropathies were confirmed in over 40% of the cases. From among these a previously poorly defined entity (hereditary motor and sensory neuropathy of neuronal type with onset in early childhood) was delineated. It constituted 7.2% of the cases. When clinical and neurophysiological investigations of the family are combined with histopathological investigation of the affected child, a correct aetiological diagnosis can be reached in over 80% of cases of chronic polyneuropathy in childhood.

The response of plasma immunoreactive (IR)-ACTH, IR-beta-endorphin (beta-END) and IR-cortisol to insulin-induced hypoglycaemia, an acute stimulus to the pituitary corticotrophs through the central nervous system, and to synthetic ovine corticotrophin-releasing hormone (CRH), a direct corticotroph stimulator, were studied in normal males and males with myotonic dystrophy. Myotonics had an increased IR-ACTH and IR-beta-END response to hypoglycaemia and an increased IR-ACTH response to CRH compared with normals. Plasma IR-cortisol response were not different in either group of subjects to both stimuli. This neuroendocrine abnormality in myotonic dystrophy may represent a manifestation of the purported specific cell membrane defect underlying the disease. This is the first report of an abnormality in proopiomelanocortin peptide release in myotonic dystrophy.

Fatigue is defined as the failure of muscle to produce the initial peak force. This may be due to failure at one or more sites between the motor cortex, the motoneuron and the internal machinery of the muscle fibre. Issues of the topic under consideration include sensation of motor command during fatigue, voluntary activation of motoneuron pools and motor unit behaviour and electromyographic activity during fatigue. At one end of this motor chain there may be failure to generate an adequate descending voluntary drive to the motoneuron pool causing central fatigue and at the other a failure of excitation-contraction coupling. The contractile apparatus within the cell may also be abnormal. Changes in the central motor commands, the discharge of motoneurons and the output of muscle fibres during muscle fatigue are described.

The structural unit of muscle has long been defined as the myofibril, a supramolecular assembly of a dozen or more proteins of which two, actin and myosin, comprise more than 75%. In the past 40 years since Albert Szent-Gyorgyi first described the contractile response from the complex of actin and myosin, knowledge of the structure and function of these contractile proteins has been substantially refined. This paper describes these new discoveries and identifies the problems which remain to be elucidated.

Membrane channels so far characterized at the single channel level and their possible involvement in muscle dysfunction are reviewed. Experiments using isolated external intercostal muscle from a patient with Torbergsen syndrome and isolated rat muscles with chemically induced myotonia suggest further involvement of membrane channels in muscle disease. Both the presence of unusual channels and the absence of normal channels can confer properties on the sarcolemmal and sarcoplasmic reticular membranes which give rise to peculiar and distinctive defects in muscle behaviour.

Muscle is a complex sensory organ as well as a contractile apparatus, and disease processes that produce muscle weakness and wasting will affect the sensory information transmitted by receptors in muscle. In addition, one of the sensory structures in muscle, the muscle spindle, receives a motor innervation, the gamma-efferent or fusimotor system, with which the brain can alter the feedback that it receives from muscle. Muscle spindle activity forms the afferent limb of spinal reflexes, such as the tendon jerk, and long-loop reflexes that traverse supraspinal reflex pathways. Muscle spindle activity constitutes the major afferent cue for kinaesthetic sensations and contributes to updating the centrally generated programme for movement. This paper reviews briefly some aspects of muscle spindle activity and its fusimotor control as studied in human subjects using microneurography.

Thirty-four Duchenne and Becker muscular dystrophy families were initially ascertained from South Australia. These have been tested systematically with the DNA probes XJ1.1 and pERT87-15. DNA results from 21 informative families have been combined with results of CK testing. Pedigree analysis was carried out using the computer program LINKAGE to provide risk figures to potential female carriers. This simple approach separated potential carriers into low or high risk classes (familial cases) or low or moderate risk classes (isolated cases). No prenatal diagnoses were carried out. The detection of deletions in two probands out of 34 makes possible definitive prenatal diagnosis in those families. For the remaining families, prenatal diagnosis could only be offered in terms of a probability statement after linkage analysis. Risk figures presented from hypothetical pedigrees demonstrated that prenatal diagnosis by linkage usually provided reasonable reliability only where informative flanking markers are used.