Desmin-free cardiomyocytes and myocardial dysfunction in end stage heart failure

Our aim was to evaluate the desmin content in the myocardial tissue of patients with end-stage heart failure of ischaemic origin and to assess its role on cardiac function. We studied 18 explanted hearts from patients transplanted for end-stage heart failure due to ischaemic cardiomyopathy (ICM). Control myocardial tissue was obtained from the cardiac biopsies of six women with breast cancer taken prior to commencing chemotherapy with anthracyclines, four male donors for heart transplantation and two autoptic hearts from patients who died due to non-cardiac events. Myocardial tissue, obtained from the left ventricle (remote zone from infarcted area), was analyzed by light and confocal immunochemistry (desmin) microscopy. The desmin content of myocardial tissue was obtained by real-time PCR. Cardiac function was evaluated by echocardiographic and right heart catheterization data, obtained before heart transplantation. Confocal microscopy evaluation showed a significant decrease in the number of desmin-positive myocytes (P<0.01) in ICM hearts compared to controls. At real-time PCR evaluation, there was a reduction (P<0.01) in desmin content in the ICM patients compared to controls. A negative correlation was found between desmin-free cardiomyocytes and ejection fraction (EF) (r=-0.834; P<0.02) on echocardiogram. A negative relationship (r=-0.688) was also found between desmin-negative myocytes and capillary wedge pressure. In conclusion, the myocardial tissue of patients with end-stage heart failure of ischaemic origin, shows a decreased number in desmin-positive myocytes at immunochemistry evaluation compared to normal individuals. This deficiency in cytoskeletal intermediate filament content is associated with reduced cardiac function. © 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved

Fenotipo clinico, valutazione immunologia e analisi molecolare in pazienti affetti da trombocitemia isolata X-recessiva (XLT)

17nonenoneNOTARANGELO L.D; GILIANI S; MORATTO D; MAZZA C; SORESINA A; C. D'IPPOLITO; TETTONI K; SORESIAN R; VERDONI L; RICCI F; MEDA SPACCAMELA; NORIS P; JANKOVIC M; LA DOGANA S; COSSU F. DE MATTIA D; NOTARANGELO L.D; PORTA FNOTARANGELO L., D; Giliani, Silvia Clara; Moratto, D; Mazza, C; Soresina, A; D'Ippolito, Carmelita; Tettoni, K; Soresian, R; Verdoni, L; Ricci, F; Meda, Spaccamela; Noris, P; Jankovic, M; LA DOGANA, S; COSSU F., DE MATTIA D; NOTARANGELO L., D; Porta, F

Effects of levetiracetam on EEG abnormalities in juvenile myoclonic epilepsy.

PURPOSE: A multicenter, prospective, long-term, open-label study to evaluate the effects of levetiracetam on electroencephalogram (EEG) abnormalities and photoparoxysmal response (PPR) of patients affected by juvenile myoclonic epilepsy (JME). METHODS: Forty-eight patients with newly diagnosed JME (10) or resistant/intolerant (38) to previous antiepileptic drugs (AEDs) were enrolled. After an 8-week baseline period, levetiracetam was titrated in 2 weeks to 500 mg b.i.d. and then increased to up to 3,000 mg/day. Efficacy parameters were based on the comparison and analysis of EEG interictal abnormalities classified as spikes-and-waves, polyspikes-and-waves, and presence of PPR. Secondary end point was evaluation of EEG and PPR changes as predictive factors of 12-month seizure freedom. RESULTS: Overall, mean dose of levetiracetam was 2,208 mg/day. Mean study period was 19.3 +/- 11.5 months (range 0.3-38). During the baseline period, interictal EEG abnormalities were detected in 44/48 patients (91.6%) and PPR was determined in 17/48 (35.4%) of patients. After levetiracetam treatment, 27/48 (56.2%) of patients compared to 4/48 (8.3%) in the baseline period (p < 0.0001) had a normal EEG. Thirteen of 17 (76.4%) (p < 0.0003) patients showed suppression of PPR. Cumulative probability of days with myoclonia (DWM) 12-month remission was significantly higher (p < 0.05) in patients with a normal (normalized) EEG after levetiracetam treatment compared to those with an unchanged EEG. CONCLUSIONS: Levetiracetam appeared to be effective in decreasing epileptiform EEG abnormalities, and suppressing the PPR in JME patients. This effect, along with a good efficacy and tolerability profile in this population further supports a first-line role for levetiracetam in the treatment of JME