Selective and Nonselective Susceptibility of Muscle Fiber Types

Engel, W. King

doi:10.1001/archneur.1970.00480200003001

Cited by 238 publications

(71 citation statements)

References 48 publications

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“…Open muscle biopsies, taken from the quadriceps muscle, were fresh-frozen in isopentane, cooled to -160°C in liquid nitrogen, and processed for muscle enzyme histochemistry as described (22). Muscle carnitine was measured as described (23).…”

Section: Louis Mo)mentioning

confidence: 99%

Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome.

Bernardini¹,

Rizzo²,

Dalakas³

et al. 1985

J. Clin. Invest.

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Plasma and urine free and acyl carnitine were measured in 19 children with nephropathic cystinosis and renal Fanconi syndrome. Each patient exhibited a deficiency of plasma free carnitine (mean 11.7±4.0 [SDI nmol/ml) compared with normal control values (42.0±9.0 nmol/ml) (P < 0.001). Mean plasma acyl carnitine in the cystinotic subjects was normal. Four subjects with Fanconi syndrome but not cystinosis displayed the same abnormal pattern of plasma carnitine levels; controls with acidosis or a lysosomal storage disorder (Fabry disease), but not Fanconi syndrome, had entirely normal plasma carnitine levels. Two postrenal transplant subjects with cystinosis but without Fanconi syndrome also had normal plasma carnitine levels. Absolute amounts of urinary free carnitine were elevated in cystinotic individuals with Fanconi syndrome. In all 21 subjects with several different etiologies for the Fanconi syndrome, the mean fractional excretion of free carnitine (33%) as well as acyl carnitine (26%) greatly exceeded normal values (3 and 5%, respectively). Total free carnitine excretion in Fanconi syndrome patients correlated with total amino acid excretion (r = 0.76). Two cystinotic patients fasted for 24 h and one idiopathic Fanconi syndrome patient fasted for 5 h showed normal increases in plasma fl-hydroxybutyrate and acetoacetate, which suggested that hepatic fatty acid oxidation was intact despite very low plasma free carnitine levels. Muscle biopsies from two cystinotic subjects with Fanconi syndrome and plasma carnitine deficiency had 8.5 and 13.1 umol free carnitine per milligram of noncollagen protein, respectively (normal controls, 22.3 and 17.1); total carnitines were 11.8 and 13.3 nmol/mg noncollagen protein (controls 33.5, 20.0). One biopsy revealed a mild increase in lipid droplets. The other showed mild myopathic features with variation in muscle fiber size, small vacuoles, and an increase in lipid droplets. In renal Fanconi syndrome, failure to reabsorb free and acyl carnitine results in a secondary plasma and muscle free carnitine deficiency.

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Section: Louis Mo)mentioning

confidence: 99%

Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome.

Bernardini¹,

Rizzo²,

Dalakas³

et al. 1985

J. Clin. Invest.

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“…This finding is nonspecific and is commonly associated with either disuse atrophy 20 or corticosteroid therapy 21 but has been described in the context of MH. 7,22 Other histologic characteristics, including myonuclear internalization4 and necrosis, 7 which have been purported to be due to focal ''mini crises'' following a MH reaction, 23 were uncommon in our patient pool.…”

Section: Discussionmentioning

confidence: 96%

Analysis of histomorphology in malignant hyperthermia-susceptible patients

Orlov

Keith

Rosen

et al. 2013

Can J Anesth/J Can Anesth

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Background Malignant hyperthermia (MH) is a potentially lethal disorder of skeletal muscle triggered by anesthetic agents. A histomorphological examination of diseased muscle may provide insight into MH pathophysiology, but it is not a routine part of standardof-care practice for the identification of MH-susceptibility. In this study, we investigated muscle histomorphology in a large cohort of MH-susceptible (MHS) patients and examined its relationship to genotype and phenotype.Methods All consenting patients who were identified as MHS based on a caffeine-halothane contracture test (CHCT) performed during 1992-2011 were retrospectively identified and recruited for this study. Results of the histomorphological examination, which is a routine part of our centre-specific practice, were reviewed. Patient demographics, MH proband status, histological features, CHCTs, and genetic results for MH-causative mutations were summarized. Results Seven of the 399 patients classified as MHS had histological characteristics consistent with central core disease, and one patient was a carrier of Duchenne's muscular dystrophy. Eighty-six (22%) patients had histological abnormalities, and five (6%) of these had evidence of ''frank'' myopathy. No histologic abnormalities were consistent among the MHS patients; however, a higher proportion of MH probands had abnormal histomorphology compared with the general MHS population, and patients with evidence of ''frank'' myopathy showed similarities in clinical history, biochemistry, CHCT, and genetic testing. Author contributions David Orlov and Sheila Riazi participated in the analysis and interpretation of data. David Orlov wrote the original draft. David Orlov, Julia Keith, Derek Rosen, Sidney Croul, and Sheila Riazi were involved with the critical revision of the original manuscript. Julia Keith, Derek Rosen, Sidney Croul, Natalia Kraeva, and Sheila Riazi were involved with the acquisition of data. Julia Keith and Sidney Croul were involved with the analysis and interpretation of the histomorphological results. Derek Rosen, Natalia Kraeva, and Sheila Riazi were involved with the conception and design of the study.

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“…Muscle carnitine was measured as described (1 5). Open or needle muscle biopsies, taken from the quadriceps muscle, were fresh-frozen in isopentane, cooled to -160°C in liquid nitrogen, and processed for oil-red-0 staining, as described (16). Creatinine was assayed by a modification of the Jaffe reaction ( 17).…”

Section: Materials a N D Methodsmentioning

confidence: 99%

Muscle Carnitine Repletion by Long-Term Carnitine Supplementation in Nephropathic Cystinosis

et al. 1993

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ABSTRACT. The renal tubular Fanconi syndrome of children with nephropathic cystinosis causes plasma and musle carnitine depletion. L-Carnitine replacement therapy for up to 18 mo has previously been shown to normalize plasma but not muscle carnitine levels. We treated six cystinosis patients, aged 1 to 4 y, with a mean dosage of 92 mg Lcarnitine/kg/d given every 6 h for an average of 62 mo. Despite fractional excretions of free carnitine ranging from 55 to 108%, plasma-free and total carnitine concentrations were maintained at or above normal levels. At the end of the carnitine replacement period, the six children had muscle-free carnitine values ranging from 16.0 to 28.0 nmol/mg noncollagen protein compared with values of 3.0 to 11.4 for cvstinosis children not s u~~l e m e n t e d with carnitine [normil, 22.7 f 5.0 (SD) nmbi/mg protein]. Total muscle carnitine values were also normalized by L-carnitine replacement. The monthly increase in total body creatinine production, a measure of muscle mass, was higher ( p = 0.036) in children with normal plasma free carnitine concentrations (3.4 f 0.9 mg/d) than in children with low plasma free carnitine (2.3 f 0.7 mg/d). No serious side effects, such as severe diarrhea, were observed. We conclude that oral L-carnitine replacement can normalize muscle carnitine content in children with cystinosis. (Pediatr Res 34: 115-1 19,1993) Carnitine, or 8-hydroxy-trimethylaminobutyric acid, mediates the transport of long-chain fatty acids into the mitochondria1 matrix for subsequent catabolism by @-oxidation to produce energy (1, 2). This process is essential for skeletal muscle (3), which serves as a large reservoir for carnitine (4) but cannot itself synthesize this molecule. Rather, carnitine is synthesized in the liver, kidney, and brain from methionine and lysine (I), and is also supplied by gastrointestinal absorption after the ingestion of meats and milk. Carnitine exists either free or esterified to fatty acids, primarily as acetylcarnitine (1).In normal individuals, free carnitine is filtered by renal glomeruli and is 97% reabsorbed by the kidney tubules (5). Patients with renal Fanconi syndrome, however, fail to reabsorb carnitine (5, 6) along with other small molecules including water, glucose, amino acids, phosphate, calcium, magnesium, sodium, potassium, and bicarbonate. Typically, free carnitine is only 67% reabsorbed in Fanconi syndrome, resulting in low plasma carni-

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Selective and Nonselective Susceptibility of Muscle Fiber Types

Cited by 238 publications

References 48 publications

Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome.

Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome.

Analysis of histomorphology in malignant hyperthermia-susceptible patients

Muscle Carnitine Repletion by Long-Term Carnitine Supplementation in Nephropathic Cystinosis

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