Muscle fiber necrosis

Muscle biopsy is usually undertaken to confirm the provisional clinical diagnosis. Because the skin lesions normally precede those in muscle, biopsies of muscle taken early may show little abnormality. Inflammatory foci may be scanty or absent and muscle fiber diameters may be normal. However typical biopsies show discrete foci of inflammatory cells, with a predominance of B-lymphocytes (see Figure 18). These cells are situated in perimysial connective tissue rather than in the en-domysium and are often also perivascular in location. Muscle fiber necrosis occurs in JDM but muscle fibers do not appear to be the primary target of the disordered immune process. Rather, it is the micro vasculature of the muscle which appears to degenerate first and muscle necrosis is preceded by capillary necrosis, detectable at the ultrastructural level. 

Various syndromes associated with hypereosinophilia involve skeletal muscle. There is a rare form of polymyositis which is characterized by this feature (defined as exceeding 1,500 eosinophils/mm for at least six months). Clinical presentation includes skin changes, heart and lung involvement, and peripheral neuropathy as well as proximal myopathy. The condition must be distinguished from trichinosis and other parasitic infections associated with hypereosinophilia. Muscle biopsy findings are interstitial and perivascular infiltrates in which eosinophils predominate but are accompanied by lymphocytes and plasma cells, and occasional muscle fiber necrosis. Fascitis may also be associated with hypereosinophilia (Shulman s syndrome). This condition is characterized by painful swelling of skin and soft tissues of trunk and extremities and weakness of limb muscles. Biopsy of muscle... 

Spencer, M.J., and Tidball, J.G., 1996, Calpain translocation during muscle fiber necrosis and regeneration in dystrophin-deficient mice, Exp Cell Res, 226, pp 264—272. 

Poisoning by anticholinesterase OP nerve agents is often characterized by abnormal muscle activity (such as fasciculations) and myopathy (muscle fiber necrosis). The severity of necrosis appears to be correlated with the frequency and duration of the fasciculations. Gupta et al. (1985, 1986, 1987) and Misuhs et al. (1987) demonstrated that both soman and DFP produced musele toxieity, although soman had its predominant aetion through CNS... 

Our group compared in Wistar rats the acutely toxic organophosphate (OP) paraoxon with fenthion, one of the agents frequently involved in human IMS. The clinical symptoms, the occurrence of muscle fiber necrosis and histochemical assessment of neuromuscular junction AChE activity in muscle biopsies, biochemical assessment of brain AChE activity, and EMG parameters including repetitive nerve stimulation at various frequencies were studied at various lime points. 

The syndrome invariably coincides with sustained AChE inhibition and is not due to muscle fiber necrosis, No separate structure-activity relationship is involved. 

TABLE 1. Prevention of DFP-induced Increase in TBA-MDA and Muscle Fiber Necrosis in Rat Diaphragm by d-Tubocurarine and U-78517F ... 

Vanneste, Y and Lison, D, (1993). Biochemical changes associated with muscle fiber necrosis after experimental organophosphate poisoning. Hum. Kxp. Toxicol. 12, 365-370. 

Assuming that intermediate syndrome (IMS) is a consequence of ACh accumulation at the neuromuscular junction, oxime cholinesiera.se reactivators. should protect again.st the development of IMS. It is noteworthy, and possibly relevant, that 2-PAM methylsulfate was reported to protect against the development of muscle fiber necrosis consequent on exposure to OP pesticides (Cavaliere el al., 1998). 

In h-IBM the terminating cellular process, either necrotic or apoptotic, that is primarily responsible for the progressive reduction of muscle bulk, has not been unequivocally elucidated. Indeed, h-IBM muscle fiber necrosis is an infrequent feature found in... 

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