Skeletal muscle pathology in AIDS: An autopsy study

Wrzolek, Monika; Sher, Joanna; Kozlowski, Piotr B.; Rao, Chandrakant

doi:10.1002/mus.880130607

Cited by 68 publications

(18 citation statements)

References 16 publications

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“…When the breakdown of skeletal muscle protein occurs faster than protein synthesis, there is a net loss of muscle protein, leading to skeletal muscle atrophy [18]. Skeletal muscle atrophy is a devastating condition and a strong predictor of morbidity and mortality in many chronic diseases, such as cancer [5], acquired immune deficiency disease (AIDS) [54], chronic obstructive pulmonary disease (COPD) [14] and amyotrophic lateral sclerosis (ALS) [27]. Therefore, there is need for therapeutic agents that target the molecular mechanisms regulating skeletal muscle mass.…”

Section: Introductionmentioning

confidence: 99%

G-CSF treatment can attenuate dexamethasone-induced reduction in C2C12 myotube protein synthesis

et al. 2015

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Section: Introductionmentioning

confidence: 99%

G-CSF treatment can attenuate dexamethasone-induced reduction in C2C12 myotube protein synthesis

et al. 2015

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“…1,[3][4][5] Risk factors recognized for NAM include statin exposure, [6][7][8][9] connective tissue disease (CTD), 1,10 cancer, 10,11 and, rarely, human immunodeficiency virus infection. 12 Recognized serum autoantibody markers 7,8,13 are specific for components of the endoplasmic reticulum-associated signal recognition particle (SRP) in the protein synthetic pathway 14,15 or for 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), 7,8,13 the rate-controlling enzyme of the mevalonate pathway involved in cholesterol synthesis. The cause of NAM is presumed to be autoimmune on the basis of subacute onset, clinical response to immunotherapy, and serum autoantibody profile.…”

mentioning

confidence: 99%

Clinical Features and Treatment Outcomes of Necrotizing Autoimmune Myopathy

et al. 2015

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IMPORTANCE Necrotizing autoimmune myopathy (NAM) is characterized pathologically by necrotic muscle fibers with absent or minimal inflammation. It is often accompanied by statin therapy, connective tissue diseases, cancer, and autoantibodies specific for signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Data are limited concerning differences among etiologic subgroups and treatment outcomes in NAM. OBJECTIVES To describe the clinical, serologic, and electrophysiologic characteristics of NAM, compare patient subgroups, and determine clinical outcome predictors. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective review of medical records for 63 adult Mayo Clinic patients assigned the clinical and histopathologic diagnosis of NAM from January 1, 2004, through December 31, 2013. Patients were stratified by presumed cause and autoantibody status. MAIN OUTCOMES AND MEASURES Clinical, electrophysiologic, and pathologic characteristics were collected and compared among patient subgroups. Predictors of response to treatment were identified by univariate logistic regression. RESULTS Lower extremity weakness predominated (46 [73%]). Distal weakness (26 [41%]), dysphagia (22 [35%]), and dyspnea (23 [37%]) were common. Twenty-two patients (35%) were receiving a statin medication at onset, 6 had cancer, and 3 had a connective tissue disease. The median creatine kinase level was 5326 U/L. In 13 patients (24%), SRP-IgG was detected, and in 17 patients (34%), HMGCR-IgG was detected (one-third of whom had not received statin medication). One patient was dual seropositive. Facial weakness was more common in SRP-IgG-positive patients. Myotonic discharges were more common in statin-associated NAM. Prednisone monotherapy was insufficient to control disease in most patients; 30 (90%) of 32 patients required 2 or more immunotherapeutic agents. Relapse occurred in 16 (55%) of 29 patients during immunosuppressant taper or discontinuation. Predictors of favorable outcome were male sex and use of 2 or more immunotherapeutic agents within 3 months of onset.CONCLUSIONS AND RELEVANCE Necrotizing autoimmune myopathy was idiopathic in half of this cohort with clinical and histopathologically defined disease. In the remainder, NAM was associated with statin medication, cancer, or connective tissue disease. One in 4 patients was SRP-IgG positive, and 1 in 3 was HMGCR-IgG positive. The disease was usually not controlled by corticosteroid monotherapy. Presentation, course, and outcomes did not differ significantly in seropositive, seronegative, and statin-associated cases. Early aggressive immunosuppressant therapy improved outcomes, and risk of relapse was high during medication dose reduction or withdrawal.

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“…In addition there are the problems of AIDS wasting syndrome with loss of muscle mass, HIV polymyositis, Zidovudine therapy induced mitochondrial myopathy and myositis (MacArthur et al 1993, Sheik et al 1999, Stringer 2000. At autopsy, 70 % of AIDS victims show microscopic abnormalities of muscles (Wrzolek et al 1990).…”

Section: Skeletal Musclementioning

confidence: 99%

HIV - implications for exercise in treatment and rehabilitation

Mars¹

2004

South African Journal of Physiotherapy

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Exercise is an integral part of many forms of rehabilitationfollowing muscle injury or surgery. It is usual to advise patients with a viral infection to avoid exercise because of the risk of developing myocarditis. Should HIV+ patients should be encouraged to undertake exercise as part of rehabilitation and should they further be advised to participate in regular exercise? There is sufficient evidence to support the benefits of regular exercise in the HIV+ patient. They will experience a training effect dependent on the normal parameters of frequency, intensity, duration, and mode of exercise. The disease does place potential limitations to exercise, as the HI virus directly affects pulmonary, cardiac, skeletal muscle and endocrine function. The effects of these changes may be exacerbated by secondary infection and other pathological changes may be induced by treatment. The advent of highly active antiretroviral therapy has brought with it a range of metabolic changes that may also influence exercise participation. The limitations to exercise imposed by HIV infection and its treatment are reviewed.

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Skeletal muscle pathology in AIDS: An autopsy study

Cited by 68 publications

References 16 publications

G-CSF treatment can attenuate dexamethasone-induced reduction in C2C12 myotube protein synthesis

G-CSF treatment can attenuate dexamethasone-induced reduction in C2C12 myotube protein synthesis

Clinical Features and Treatment Outcomes of Necrotizing Autoimmune Myopathy

HIV - implications for exercise in treatment and rehabilitation

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