Toxic Myopathy Research Articles

Mitochondrial Myopathy Caused by Long-Term Zidovudine Therapy

Both infection with the human immunodeficiency virus type 1 (HIV) and zidovudine (formerly called azidothymidine [AZT]) cause myopathy. To identify criteria for distinguishing zidovudine-induced myopathy from that caused by primary HIV infection, we reviewed the histochemical, immunocytochemical, and electron-microscopical features of muscle-biopsy specimens from 20 HIV-positive patients with myopathy (15 of whom had been treated with zidovudine) and compared the findings with the patients' clinical course and response to various therapies. Among the zidovudine-treated patients, the myopathy responded to prednisone in four, to the discontinuation of zidovudine in eight, and to nonsteroidal anti-inflammatory drugs in two. Numerous "ragged-red" fibers, indicative of abnormal mitochondria with paracrystalline inclusions, were found in the biopsy specimens from the zidovudine-treated patients but not in those from the other patients. The number of these fibers appeared to correlate with the severity of the myopathy. All the patients, regardless of whether they had been treated with zidovudine, had inflammatory myopathy characterized by degenerating fibers, cytoplasmic bodies, and endomysial infiltrates consisting of CD8+ cells (mean +/- SD, 60.7 +/- 6.4 percent) and macrophages (39.2 +/- 6.4 percent) associated with Class I major histocompatibility complex (MHC-I) antigens (HLA-A, -B, and -C antigens) in the muscle fibers. The numbers and percentages of CD8+ cells and macrophages were similar in both the zidovudine-treated and the untreated HIV-positive patients. Specimens obtained on repeat muscle biopsy from two patients in whom the myopathy responded to the discontinuation of zidovudine showed remarkable histologic improvement. We conclude that long-term therapy with zidovudine can cause a toxic mitochondrial myopathy, which coexists with a T-cell-mediated inflammatory myopathy that is restricted to MHC-I antigen, and is indistinguishable from the myopathy associated with primary HIV infection or polymyositis in HIV-seronegative patients.

Serum Enzymes in Disease of Skeletal Muscle

Creatine kinase is the serum enzyme that shows the greatest frequency of abnormality in skeletal muscle disease. Changes in this enzyme in sex-linked dystrophy (Duchenne's and Becker's) patients and carriers; in patients with other dystrophies; and in inflammatory, toxic, endocrine, and traumatic myopathy are reviewed. The changing role of serum enzyme measurements as a consequence of newer methods of genetic diagnosis is also considered.

Reversible emetine-induced myopathy with ECG abnormalities: a toxic myopathy

A young anorexic woman is described with a history of progressive muscle weakness following chronic ingestion of syrup of ipecac that was used in an attempt at weight control. Electrocardiogram (ECG) showed T-wave inversion in all leads and prolongation of the Q-T interval. Electromyography was abnormal. Muscle biopsy revealed a randomized, generalized, predominantly type-2 fibre atrophy and structural alterations in oxidative enzyme stains, such as targetoid and moth-eaten fibres. A few necrotic cells were actively phagocytosed. Electron microscopy revealed severe sarcomeric abnormalities with Z-line streaming, myofibrillar disorganization and increased lysosomal activity. After discontinuation of ipecac syrup, the patient noted a gradual improvement in her condition. The ECG became normal. Emetine and related drug-induced myopathies are uncommon but are of experimental interest because of their effects on mitochondria and the light they shed on autophagic mechanisms in muscle.

Toxic Myopathies

Toxic myopathies are commonly unrecognized. An understanding of the mechanism by which toxins produce disease, identification of risk factors that predispose patients to myopathy, and recognition of a few special clinical syndromes will greatly enhance the clinician’s ability to detect these disorders.

Spontaneous primary myopathies in domestic mammals: a review.

By reviewing the literature concerning primary myopathies in man and animals, a classification of spontaneous primary myopathies in domestic mammals is made. This classification is based on aetiological factors. Primary myopathies are divided into metabolic, immunologic, toxic, nutritional, congenital, inherited, and inflammatory myopathies. Muscular dystrophies, in accordance with the definition in human cases, are considered as a separate entity. In the description of the different muscle disorders the emphasis is on the structural changes and the pathogenesis. Clinical signs and diagnostic criteria are considered only briefly.

Chloroquine neuromyotoxicity. Clinical and pathologic perspective

Six cases of toxic myopathy and/or neuropathy with chloroquine and/or hydroxychloroquine therapy are described. Two patients had unique clinical and pathologic evidence of cardiomyopathy secondary to chloroquine or hydroxychloroquine therapy. One patient had polyneuropathy secondary to chloroquine toxicity. This may be the first documentation of several features of chloroquine/hydroxychloroquine toxicity: (1) morphologic changes in human peripheral nerve in chloroquine toxicity; (2) chloroquine/hydroxychloroquine cardiomyopathy diagnosed by endomyocardial biopsy; and (3) hydroxychloroquine myotoxicity. Chloroquine is a neuromyotoxin that affects nerves and cardiac and skeletal muscles. Discontinuation of chloroquine and hydroxychloroquine resulted in marked improvement in most cases. The reversibility of the symptoms emphasizes the importance of recognizing potential signs of nerve, muscle, and cardiac toxicity in patients being treated with chloroquine or hydroxychloroquine.

Drug-Induced and Toxic Myopathies

Drug-Induced and Toxic Myopathies

Toxic Myopathy in Dairy Cattle Causes by Cassia obtusifolia in Greenchop

Toxic Myopathy in Dairy Cattle Causes by Cassia obtusifolia in Greenchop

Disuse atrophy of muscle; histochemistry and electron microscopy.

THE application of refined morphologic techniques to human neuromuscular disorders in recent years produced greater diagnostic accuracy in established diseases and recognition of increasing numbers of previously undescribed disorders. Unfortunately, many of these recent observations provide no clear-cut explanation of, or obvious application to, the pathogenesis of neuromuscular disease. When applied to classical experimental conditions in animals, these same methods allow more meaningful observations of cause and effect. Several investigators1-3studied the effect of denervation on histochemical staining of various types of muscle fibers. Pellegrino and Franzini4investigated similar stages of denervation with electron microscopic techniques. Engel et al5reported the histochemical investigation of muscle after tenotomy, while Walker and his coworkers6have published related electron microscopic observations. Karpati and Engel7investigated the effects of cordotomy on muscle by histochemical techniques. Various toxic myopathies have received considerable attention in the ultrastructural literature. Little attention

DIAGNOSIS AND TREATMENT: USE OF STEROIDS IN ASTHMA IN CHILDREN

ALTHOUGH cortisone and its derivatives have been widely and increasingly used in the management of allergic conditions during the past fifteen years, no final judgment has been reached as to their place in management of asthma, either in adults or in children. The seriousness of unresolved questions is well exemplified in the discussion by Alexander, Samter, Arbesman, and others as to whether mortality in asthma has fallen or risen since corticosteroid drugs became available. Without taking sides we can acknowledge that because these agents are both effective and hazardous, their use poses a dilemma. The therapeutic effects of steroids have not been easily separated from their undesired side effects, particularly in prolonged use. Table I lists the better-known effects of chronic administration. The likelihood of each effect varies with the drug used, the effects on fluid and electrolyte economy having been particularly well separated in some agents from the anti-inflammatory effects. It has not been possible, however, to attain adequate anti-inflammatory effects without some stimulation of protein catabolic processes or without some evidence of increased susceptibility to infection or to adrenal suppression. The subtle nature of symptoms of infection in patients receiving steroid therapy may lead to disastrous delays in diagnosis, and have given rise to the legendary patient receiving steroid therapy who "walks to his place on the autopsy table." Certain side effects are more or less specific features of certain agents, such as the marked stimulation of appetite, the weight gain, and the euphoria associated with dexamethasone, or the anorexia, depression, and toxic myopathy associated with triamcinolone. Sometimes a distressing side effect may be avoided by change in agent; highly soluble prednisolone phosphate appears, for example, less likely than prednisolone to stimulate peptic ulceration.