Inclusion body myositis. A corticosteroid-resistant idiopathic inflammatory myopathy.

In seven patients with slowly progressive muscle weakness, inclusion body myositis (IBM) was diagnosed on biopsy. None had stigmata of collagen-vascular disease or malignancy. Serum creatine kinase levels were mildly or moderately increased. The six patients treated with prednisone did not improve. Needle electromyography showed a "myopathic" pattern in all patients, but four also had diffuse neurogenic changes with normal nerve conductions. Histologic study of muscle showed a mixture of small rounded fibers varying in size, atrophic angulated fibers forming small groups, and hypertrophic fibers. Variable amounts of inflammation, necrosis, and regeneration were seen in all specimens. All showed numerous intracytoplasmic vacuoles lined with purple-blue granules. Electron microscopy showed membranous whorls and masses of abnormal filaments measuring 14 to 18 nm in diameter. Although IBM seems to be a distinct type of inflammatory myopathy, its etiology and pathogenesis are not clear.

Reduction in insulin receptors in amyotrophic lateral sclerosis correlates with reduced insulin sensitivity.

Abnormal glucose and insulin metabolism have often been reported in patients with amyotrophic lateral sclerosis. Recently, we have demonstrated reduced insulin sensitivity in this disease and suggested that muscle wasting was not the principal determinant of this reduction. In the current studies, insulin binding to circulating mononuclear leukocytes from 10 amyotrophic lateral sclerosis patients and 16 controls were compared. The relative capacity and affinity of monocyte insulin binding sites were estimated, and simultaneous plasma insulin levels were also obtained. A 2 1/2-fold reduction in the number of binding sites (percent 125I-insulin bound to monocytes) was found in the patients compared with controls (p = 0.001). No differences were obtained when ED50 plots (relative affinity) were compared (p = 0.5). Ideal body weight was similar in both groups (approximately 100%) and plasma insulin levels were not elevated in the patients, suggesting that "down-regulation" from increased ambient hormone levels was not a factor in the lowered receptor numbers. A definite correlation was not found when numbers of insulin receptors were compared with disease progression, body weight, or plasma insulin levels. However, future studies with larger numbers of patients along with quantitation of disease progression may indicate such a trend.

Environmental influence on altered receptor function in a genetic disease: insulin and glucose affect insulin receptors in myotonic dystrophy.

Insulin action in vivo and insulin binding to monocytes in vitro were correlated in patients with myotonic dystrophy (MyD) and compared with healthy controls. Confirming our previous studies and those of others, the present results show that the glucose infusion rate (DR), an estimate of in vivo insulin sensitivity, was significantly diminished in MyD. At the same per cent of ideal body weight DR in MyD patients was considerably less than controls suggesting that obesity could not solely account for decreased insulin sensitivity in MyD. The relative capacity (RC), and relative affinity (ED50) of the insulin receptor in monocytes was significantly less in patients. The relative affinity (ED50) was improved by changing environmental insulin levels while receptor numbers (RC) were not. Insulin sensitivity and RC showed a trend toward a positive correlation although this did not reach statistical significance. Our data suggest that the alteration of the insulin receptor in MyD is different from obesity and from other disorders of the motor unit such as amyotrophic lateral sclerosis, where insulin sensitivity and RC are reduced but ED50 is unchanged. Thus, in MyD the receptor may be one of the loci where the resistance occurs.

Insulin resistance in amyotrophic lateral sclerosis.

Over the last 30 years glucose intolerance has been reported in a significant percentage of patients with amyotrophic lateral sclerosis (ALS). Currently, a controversy exists in determining whether the carbohydrate abnormality is disease-specific or secondary to decreased glucose utilization due to muscle atrophy. A reduction in glucose receptor space had been postulated for a number of neuromuscular diseases including ALS. In order to clarify this issue we have estimated in vivo insulin sensitivity, using the euglycemic insulin clamp technique, in ALS patients and two control groups, matched according to percent ideal weight. The results showed that the glucose infusion rate, an estimate of in vivo insulin sensitivity, ws significantly diminished in ALS patients compared to both normal and disease controls. These results demonstrate that the insulin resistance in this disorder cannot be explained by a decrease in glucose-receptor space and suggest a primary carbohydrate aberration in the disease process itself.

Lysophospholipase activity in rabbit skeletal muscle.

Skeletal muscle contains appreciable lysophospholipase activity which is differentiated by muscle type with red muscle subcellular fractions having greater activity than the corresponding white ones.

Inclusion body myositis associated with systemic sarcoidosis.

We report an autopsy study of a 64-year-old female with systemic sarcoidosis. In addition many muscles showed typical light and electron microscopic features of inclusion body myositis. To our knowledge this association has not been previously reported.

Modern therapeutic approach for high grade astrocytoma: intracranial Ir-192 brachytherapy.

Prognosis of high-grade astrocytoma has been extremely disappointing and the median survival of patients with this tumor is less than 10 months at best. The most common cause of failure is local persistence of the tumor. Many neuro-oncologists have now turned to an alternative therapeutic approach involving brain brachytherapy (interstitial implantation) for the treatment of high-grade astrocytomas because in this manner a higher dose can be delivered to the tumor bed without excessively irradiating the surrounding normal brain tissue. Brachytherapy has shown some evidence of superior results in survival of malignant astrocytomas if properly performed by a qualified brachytherapy team. The objective of this report is to discuss the rationale and technique of brachytherapy in the management of high-grade astrocytoma as well as future prospects concerning this particular treatment modality.