Evidence Of Muscle Injury Research Articles

NLA Task Force on Statin Safety--2014 update.

1933-2874/$ see front matter 2014 http://dx.doi.org/10.1016/j.jacl.2014.03 Statins are the most widely prescribed class of medications in the United States and their benefits for lowering lowdensity lipoprotein cholesterol (LDL-C) and reducing the risk for coronary heart disease (CHD) are well documented. Statins have been the cornerstone of pharmacotherapy for the management of high blood cholesterol levels virtually since their development. The American Heart Association /American College of Cardiology 2013 guidelines recently expanded the number of individuals eligible for statin therapy by recommending it for those with: (1) clinical atherosclerotic cardiovascular disease (ASCVD), (2) LDL-C $190 mg/dL, (3) type 2 diabetes and age between 40 and 75 years with LDL-C 70 to 189 mg/dL, and (4) an estimated 10-year risk of ASCVD $7.5% and age 40 to 75 years. Considering only those who qualify according to their estimated 10-year risk of ASCVD, it has been reported that of the 101 million people in the United States age 40 to 79 years who do not have cardiovascular disease, 33 million have an estimated 10-year risk of ASCVD $7.5%, and another 13 million have a risk between 5% and 7.4%. Using crude global estimates, 920 million people worldwide would be expected to be

骨格筋でのみアミロイドの沈着を確認しえたアミロイドーシスの1例

A 75-year-old man was admitted to our hospital with progressive weakness in the lower extremities for 7 months. Immunoelectrophoresis of serum detected IgA λ type M protein and bone marrow examination detected an increase in monoclonal plasma cells, thus leading to a diagnosis of IgA λ type multiple myeloma. Subsequent muscular CT scan showed severe fatty infiltration of vastus lateralis muscles, and histopathological examinations of biopsied muscle specimens an abundance of abnormal "ring-fiber-like" appearance, positive staining by Congo red and the presence of anti-λ light chain antibody. This led to a diagnosis of amyloid myopathy. No depositions were seen in rectal mucosa, cardiac muscle, or sural nerve. The results of double immunohistochemical staining using anti-dystrophin antibody and anti-λ light chain antibody suggested the possibility of direct injury by amyloid to muscle fibers. The case presented here was thus amyloidosis confirmed by deposition of amyloid only in muscles. In conclusion, when amyloidosis is suspected and there is evidence of muscle injury, muscle biopsy should be performed.

Antipsychotics

Antipsychotics

Pheochromocytoma Presenting With Myocardial Infarction, Cardiomyopathy, Renal Failure, Pulmonary Hemorrhage, and Cyclic Hypotension: Case Report and Review of Unusual Presentations of Pheochromocytoma

Pheochromocytoma Presenting With Myocardial Infarction, Cardiomyopathy, Renal Failure, Pulmonary Hemorrhage, and Cyclic Hypotension: Case Report and Review of Unusual Presentations of Pheochromocytoma

Cardiac-specific overexpression of tumor necrosis factor-alpha causes oxidative stress and contractile dysfunction in mouse diaphragm.

We have developed a transgenic mouse with cardiac-restricted overexpression of tumor necrosis factor-alpha (TNF-alpha). These mice develop a heart failure phenotype characterized by left ventricular dysfunction and remodeling, pulmonary edema, and elevated levels of TNF-alpha in the peripheral circulation from cardiac spillover. Given that TNF-alpha causes atrophy and loss of function in respiratory muscle, we asked whether transgenic mice developed diaphragm dysfunction and whether contractile losses were caused by oxidative stress or tissue remodeling. muscles excised from transgenic mice and littermate controls were studied in vitro with direct electrical stimulation. Cytosolic oxidant levels were measured with 2', 7'-dichlorofluorescin diacetate; emissions of the oxidized product were detected by fluorescence microscopy. Force generation by the diaphragm of transgenic animals was 47% less than control (13.2+/-0. 8 [+/-SEM] versus 25.1+/-0.6 N/cm(2); P:<0.001); this weakness was associated with greater intracellular oxidant levels (P:<0.025) and was partially reversed by 30-minute incubation with the antioxidant N:-acetylcysteine 10 mmol/L (P:<0.01). Exogenous TNF-alpha 500 micromol/L increased oxidant production in diaphragm of wild-type mice and caused weakness that was inhibited by N:-acetylcysteine, suggesting that changes observed in the diaphragm of transgenic animals were mediated by TNF-alpha. There were no differences in body or diaphragm weights between transgenic and control animals, nor was there evidence of muscle injury or apoptosis. Elevated circulating levels of TNF-alpha provoke contractile dysfunction in the diaphragm through an endocrine mechanism thought to be mediated by oxidative stress.

Phenotypic and immunologic factors affecting plasmid-mediated in vivo gene transfer to rat diaphragm.

Little is known about the molecular mechanisms governing adaptive responses of the diaphragm in the setting of lung disease. By permitting the study of regulatory elements and the effects of overexpressing genes of interest, direct in vivo gene transfer to the diaphragm could be used as a tool to address such questions. Therefore, we evaluated parameters affecting transfection efficiency and duration of foreign gene expression in the diaphragm after plasmid-mediated gene transfer. Reporter gene constructs were injected into adult rat diaphragm and hindlimb muscles. Transfection efficiency at 8-10 days postinjection was decreased in large caliber ( > 1,000 microns2) and type II myosin heavy chain (MHC)-expressing fibers. There were also strong trends toward augmented transfection efficiency in type I MHC- and embryonic MHC-expressing fibers. All diaphragms demonstrated evidence of muscle injury and inflammatory cell infiltrates at this early time point. By 30 days postinjection, however, neither inflammation nor reporter gene expression was detectable in diaphragm or hindlimb muscles of immunocompetent animals. By contrast, immunosuppressed rats (given cyclosporine; 15 mg.kg-1. day-1) showed high levels of foreign gene expression at 30 days postinjection, which remained stable up to 60 days. Therefore, exploitation of plasmid-mediated in vivo gene transfer as a tool for studying regulated gene expression in the diaphragm may be facilitated by the use of immunodeficient animal models.

Elevation of serum creatine kinase in divers with arterial gas embolization.

Arterial gas embolism due to pulmonary barotrauma and the resultant cerebral gas embolism are catastrophic complications of diving. Previous studies have only rarely noted evidence of gas embolism to noncranial sites. Among 142 persons with diving-related injuries evaluated between January 1982 and July 1991, we identified 29 who had arterial gas embolism and who underwent biochemical studies indicative of muscle injury. Of the 29 patients, 4 were excluded because cardiopulmonary resuscitation had been performed and 3 were excluded because the duration of their dives met or exceeded standard limits set for dives not requiring staged decompression. The outcome at the time of hospital discharge in the remaining 22 patients was correlated with clinical factors and the results of biochemical studies. We also studied 22 subjects after uncomplicated dives and 11 patients who had sustained blunt trauma. All the patients with diving-associated gas embolism had elevated serum creatine kinase activity (normal, < or = 175 U per liter); the values were markedly elevated (> 900 U per liter) in 14. The MB isoenzyme of creatine kinase was detected in the serum of 13 of 20 patients in whom it was measured and was > or = 4 percent of total creatine kinase activity in 6 patients. In three patients electrocardiography showed myocardial injury. Changes in serum creatine kinase activity of similar magnitude were not present in the subjects who had uncomplicated dives or in the patients with blunt trauma. Thirteen patients recovered fully, four had minor residual neurologic deficits, three were severely impaired, and two died. Logistic-regression analysis revealed a significant correlation between peak serum creatine kinase values and clinical outcome. Biochemical evidence of muscle injury is frequently found after diving-associated arterial gas embolism. The correlation between serum creatine kinase activity and outcome suggests that serum creatine kinase is a marker of the size and severity of arterial gas embolism.

Acute renal failure due to non-traumatic rhabdomyolysis.

Summary Seventeen patients with acute renal failure of diverse aetiology showed myoglobinuria and elevated levels of serum creatine phosphokinase (mean 119·2 Sigma u./ml) and adolase (mean 88·5 Sibley-Lehninger (SL)u./ml), indicating the presence of diffuse muscle cell injury. The primary conditions which led to rhabdomyolysis and acute renal failure were burns, eclampsia, prolonged labour, crush injury, epileptiform convulsions, status asthmaticus, viral myositis and intoxication with chemicals including copper sulphate, mercuric chloride and zinc phosphide. In 10 non-myoglobinuric patients with acute renal failure, serum creatine phosphokinase was normal (mean 8·9 Sigma u./ml) and serum aldolase was only slightly elevated (mean 11·2 SL u./ml). Although uric acid was elevated in both groups, the values were significantly higher in myoglobinuric (mean 0·728 ± 0·199 mmol/l) compared to non-myoglobinuric patients (mean 0·583 ± 0·093 mmol/l). During the oliguric phase, hypocalcaemia was observed in 82·2% of myoglobinuric patients and in 20% of non-myoglobinuric patients. Ten out of 15 patients with myoglobinuric renal failure developed hypercalcaemia during the diuretic phase whereas only 3 non-myoglobinuric patients showed a transient hypercalcaemia. Although the mean serum potassium was somewhat higher in the myoglobinuric patients, the difference between the 2 groups was not significant. It is concluded that acute renal failure associated with non-traumatic rhabdomyolysis is not infrequent and may occur in a variety of conditions where gross evidence of muscle injury is lacking.