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Limb girdle muscular dystrophy (LGMD) type 2B and distal Miyoshi myopathy (MM) are caused by mutations in a recently discovered mammalian gene coding for a skeletal muscle protein called dysferlin. The protein is normally expressed at the skeletal muscle level and absent or reduced in affected patients. We selected a clinically heterogeneous population of Italian myopathic patients with clinical evidence of myopathy and/or hyperCKemia, EMG myopathic pattern, and no alterations of the dystrophin-sarcoglycan complex. Calpain, merosin, emerin and caveolin were also tested and found normal in all patients. Dysferlin immunohistochemical and Western blot analyses allowed us to identify six patients with dysferlin deficiency: one with distal myopathy, four with limb girdle myopathy and one with hyperCKemia. No apoptosis was found in any of the six muscle specimens, although expression of the pro-apoptotic Fas antigen was mildly increased in two cases. Inflammatory reactions were present in two of the six cases, but we found no evidence of immune-mediated processes. [ABSTRACT FROM AUTHOR]

Objectives: To determine the efficacy of L-carnitine in reducing hyperammonaemia and improving neuropsychological performance in patients with hepatic cirrhosis and subclinical hepatic encephalopathy (SHE). Design: Randomised, parallel group, controlled trial. Patients and Methods: The study enrolled 31 patients with hepatic cirrhosis resulting from hepatitis C and/or hepatitis B, alcohol abuse and other causes. Patients randomised to active treatment, received oral L-carnitine 6 g/day in two divided doses for 4 weeks. Diagnosis of SHE was based on psychometric tests (subtests of the Wechsler Adult Intelligence Scale-Revised and the Halstead-Reitan Neuropsychological Test Battery) carried out at beginning and end of study. Serum ammonia levels were measured before treatment and weekly thereafter. Results: A total of 27 patients completed the study. Sixteen patients received L-carnitine and 11 served as controls (no treatment). L-carnitine caused rapid and significant reductions in ammonia levels, sustained over the 4-week treatment period (mean reductions 60.1 and 1.4 μmol/L in the treated and control groups, respectively). Normal ammonia levels were attained in 14 of 16 patients receiving L-carnitine. Based on psychometric test results, seven patients (43.7%) in the L-carnitine group and five (45.5%) in the control group had SHE at baseline. L-carnitine treatment for 4 weeks caused a net overall improvement in psychometric test results compared with controls. No clinically significant adverse events were reported and all patients receiving L-carnitine reported subjective improvements in their condition. Conclusions: Results of this preliminary study indicate that L-carnitine reduces hyperammonaemia and improves the clinical symptoms of SHE in patients with hepatic cirrhosis. [ABSTRACT FROM AUTHOR]