Quantitative histopathology of the inflammatory myopathies.

This study quantitatively assessed skeletal muscle histopathology in 57 patients with inflammatory myopathy, including 20 patients with polymyositis (PM), 19 patients with dermatomyositis (DM), and 18 patients with evidence of an additional connective-tissue disease. No histologic criteria for invariably distinguishing patients with inflammatory myopathy were established because of overlap in individual measurements, but general histopathologic distinctions were confirmed. In PM, endomysial mononuclear cell infiltration (fibers bordering on inflammation) was usual, whereas in DM inflammation of large vessels, fibers with circumscribed areas of myofibrillar loss, and perifascicular atrophy were seen. Patients with evidence of an additional connective-tissue disease were most similar to the DM patients, with a greater prevalence of perivascular inflammation than in the PM patients. Because of varying histopathology (and presumed varying pathogenesis), future therapeutic trials would be more informative if they were designed using patients with homogeneous histologic features.

Ultrastructural and histochemical abnormalities of skeletal muscle in patients with chronic vitamin E deficiency.

We report muscle biopsy abnormalities in four patients with a chronic cholestatic syndrome, low serum vitamin E levels, absent reflexes, mild limb weakness, ataxia, and sensory loss in arms and legs. Skeletal muscle fibers contained multiple autofluorescent inclusions that show strong acid phosphatase and esterase reactivity. By electronmicroscopy, the inclusions lying between myofibrils were membrane-bound dense bodies having characteristics of both lysosomes and lipopigment material. The material was similar to that observed in vitamin E-deficient animals and probably formed in response to disordered intracellular lipid peroxidation.

Mitochondrial morphometrics of histochemically identified human extraocular muscle fibers.

Three fiber types--coarse, granular, and fine--were readily identified in histochemical cryostat sections of human extraocular muscle (EOM). The cryostat retrieval method was utilized to identify these three fiber types in serial electron microscopic thin sections. Using morphometric techniques, five mitochondrial variables (mitochondrial volume fraction, mitochondrial profile size, mitochondrial profile density, and clusters of two or of three or more mitochondrial profiles) were determined for a total of 162 histochemically identified fibers from two regions (orbital and global zones) from six EOMs. Coarse fibers had numerous large-sized mitochondrial profiles, often occurring in clusters. Granular fibers had fewer and smaller-sized profiles scattered across the fiber. Fine fibers had the most numerous, but smallest-sized mitochondrial profiles. Despite significant differences in group (fiber types) means for the mitochondrial variables, no single variable was sufficient for separating fiber types into distinct populations. Although a scattergram plot of two variables was sufficient to separate orbital zone fibers, a computer-generated, multivariate discriminant analysis was needed to separate the global zone fibers into distinct populations. These results will aid future studies on normal and pathological human EOM by providing a morphometric basis for identifying fiber types in the orbital and global zones.

Distribution of capillaries in normal and diseased human skeletal muscle.

The distribution of capillaries was studied in muscle biopsies in a large number of normal subjects and in patients with disuse atrophy, inflammatory myopathies, and other chronic myopathic and neurogenic disorders. The cryostat retrieval technique was used, along with capillary and muscle fiber morphometry, to quantitate capillary distribution around specific fiber types. In all diseased and normal muscle, the number of capillaries per fiber (C/F) and the number of capillaries surrounding a fiber (CAF) increased with fiber diameter. More capillaries typically surrounded type 1 than type 2 fibers within a given group. When all inflammatory myopathy patients (polymyositis, dermatomyositis, and polymyositis plus second connective tissue disease) were compared with normal adults, their muscle biopsies had fewer capillaries per fiber over the same diameter range. The numerous variables influencing capillary number in normal and diseased muscle are discussed.