Nemaline myopathy and cardiomyopathy.

A case report is presented in which a 4-year-old male is diagnosed with hypertrophic cardiomyopathy, respiratory distress, muscle hypotonia, and psychomotor retardation. Electron microscopic study of skeletal muscle biopsy revealed pathologic changes typical of congenital nemaline myopathy, and biochemical analysis revealed a disorder of mitochondrial fatty acid oxidation. Therefore a previously undescribed combination of a structural and metabolic myopathy is reported.

Myoadenylate deaminase deficiency, hypertrophic cardiomyopathy and gigantism syndrome.

We report a 20-year-old man with gigantism syndrome, hypertrophic cardiomyopathy, muscle weakness, exercise intolerance, and severe psychomotor retardation since childhood. Histochemical and biochemical analysis of skeletal muscle biopsy revealed myoadenylate deaminase deficiency; molecular genetic analysis confirmed the diagnosis of primary (inherited) myoadenylate deaminase deficiency. Plasma, urine, and muscle carnitine concentrations were reduced. L-Carnitine treatment led to gradual improvement in exercise tolerance and cognitive performance; plasma and tissue carnitine levels returned to normal, and echocardiographic evidence of left ventricular hypertrophy disappeared. The combination of inherited myoadenylate deaminase deficiency, gigantism syndrome and carnitine deficiency has not previously been described.

A comparison of the monitors INVOS 3100 and NIRO 500 in detecting changes in cerebral oxygenation.

BACKGROUND: Measurements of cerebral haemoglobin oxygenation of 2 near-infrared spectroscopy devices (INVOS 3100 and NIRO 500) were compared during and after hypocapnia. METHODS: Fifteen awake, healthy volunteers, who hyperventilated to obtain end-tidal CO2 (EtCO2) values of approximately 20 mmHg, were studied. During hyperventilation and 8 min thereafter, EtCO2, INVOS 3100 (RSO2 = regional cerebral oxygenation) and NIRO 500 recordings (HbO2 = oxyhaemoglobin, Hb = deoxyhaemoglobin, Hb-diff = HbO2-Hb, CtO2 = oxidised cytochrome oxidase aa3) were analysed. RESULTS: Hyperventilation induced a significant decline in EtCO2 from 30.5 to 14.7 mmHg (P < 0.001) and RSO2 from 67.1% to 62.7% (P = 0.025). At hypocapnia, only Hb (+1.61 +/- 0.48 mumol/L; P < 0.001) and Hb-diff (-3.01 +/- 2.0 mumol/L; P < 0.001) indicated a decline in cerebral haemoglobin oxygenation. Within 8 min after hyperventilation, both EtCO2 and RSO2 normalised to values insignificantly different from baseline. In contrast, Hb and Hb-diff remained significantly different (Hb: +2.52 +/- 1.28 mumol/l; P < 0.001, Hb-diff: -4.31 +/- 4.0 mumol/L; P < 0.001). A correlation with EtCO2 was found for RSO2 (R = 0.35; P < 0.001) and CtO2 (R = 0.42; P < 0.001). All volunteers were continuously awake and none presented clinical symptoms of cerebral hypoxia. CONCLUSION: Changes in cerebral haemoglobin oxygenation state were reflected more accurately by INVOS 3100 than NIRO 500. The cause may be the different technology of the monitors, since INVOS 3100 eliminates the contribution of extracranial oxygenation.

IgG subclass reactivity to human cardiac myosin in cardiomyopathy patients is indicative of a Th1-like autoimmune disease.

Studies performed in mice together with the demonstration of increased levels of heart-specific autoantibodies, cytokines and cytokine receptors in sera from cardiomyopathy (CMP) patients argued for a pathogenic role of autoimmune mechanisms in CMP. This study was designed to analyse the presence of IgG anti-heart antibodies in sera from patients suffering from hypertrophic and dilatative forms of CMP as well as from patients with ischaemic heart disease and healthy individuals. Patients' sera were analysed for IgG reactivity to Western-blotted extracts prepared from human epithelial and endothelial cells, heart and skeletal muscle specimens as well as from Streptococcus pyogenes. The IgG subclass (IgG1-4) reactivity to purified human cardiac myosin was analysed by ELISA. While sera from CMP patients and healthy individuals displayed comparable IgG reactivity to a variety of human proteins, cardiac myosin represented the prominent antigen detected strongly and preferentially by sera from CMP patients. Pronounced IgG anti-cardiac myosin reactivity was frequently found in sera from patients with dilatative CMP and reduced ventricular function. ELISA analyses revealed a prominent IgG2/IgG3 anti-cardiac myosin reactivity in CMP sera, indicating a preferential Th1-like immune response. Elevated anti-cytomegalovirus, anti-enterovirus IgG titres as well as IgG reactivity to nitrocellulose-blotted S. pyogenes proteins were also frequently observed in the group of CMP patients. If further work can support the hypothesis that autoreactivity to cardiac myosin represents a pathogenic factor in CMP, specific immunomodulation of this Th1- towards a Th2-like immune response may represent a promising therapeutic strategy for CMP.