Electrical behavior of MIS devices based on Si nanoclusters embedded in SiOxNy and SiO2 films

We examined and compared the electrical properties of silica (SiO2) and silicon oxynitride (SiOxNy) layers embedding silicon nanoclusters (Sinc) integrated in metal-insulator-semiconductor (MIS) devices. The technique used for the deposition of such layers is the reactive magnetron sputtering of a pure SiO2 target under a mixture of hydrogen/argon plasma in which nitrogen is incorporated in the case of SiOxNy layer. Al/SiOxNy-Sinc/p-Si and Al/SiO2-Sinc/p-Si devices were fabricated and electrically characterized. Results showed a high rectification ratio (>104) for the SiOxNy-based device and a resistive behavior when nitrogen was not incorporating (SiO2-based device). For rectifier devices, the ideality factor depends on the SiOxNy layer thickness. The conduction mechanisms of both MIS diode structures were studied by analyzing thermal and bias dependences of the carriers transport in relation with the nitrogen content

THE NONCOMPACTION OF THE LEFT VENTRICULAR MYOCARDIUM: OUR PEDIATRIC EXPERIENCE

OBJECTIVES: The noncompaction of the left ventricular myocardium is a rare congenital heart disease, characterized by an excessive prominence of trabecular meshwork, spaced out by deep intertrabecular recesses, consequent to the arrest of the normal myocardium embryogenesis. Although there are numerous descriptions, the physiopathological effects of the structural alterations, just like the clinical spectrum and the evolution of the disease, are not totally clarified. In the present study, we have evaluated the natural history of the disease, the familial incidence and the alterations of the systolic and diastolic function. METHODS: We collected a series of 21 young patients who were affected by noncompaction of left ventricular myocardium. In all cases, a diagnosis was echocardiographically made on the basis of a reported spongy/compacted ratio > 2 in one or more segments of the left ventricle. Thirteen patients were male and eight were female, with a mean age of 12.7 years (range 21 days to 27 years). The average follow-up time was 7.8 years (range 1-18 years); all patients were periodically tested by ECG Holter and two-dimensional and Doppler echocardiogram. In 14 patients, the last echocardiographic evaluation included the analysis of tissue Doppler imaging (TDI). RESULTS: The noncompaction of left ventricular myocardium was isolated in nine cases and associated with a structural cardiopathy in 12 cases: with atrial septal defect in four cases, ventricular septal defect in four cases, aortopulmonary window in one case, aortic coarctation in one case and bicuspid aortic valve in one case. One case presented a type Kent ventricular pre-excitation. Twelve cases were symptomatic at the moment of the diagnosis (for heart failure in 11 cases and for syncope in one case). Nine cases were asymptomatic and the diagnosis was made during a family screening or occasionally. In ten of the 11 subjects affected by congestive heart failure, medical therapy re-established a good haemodynamic balance (in two cases, it was possible to suspend the therapy). In one case with congestive heart failure and pulmonary hypertension in New York Heart Association class III, we recommended heart transplantation. We did not find any dysrhythmia in any of the cases. Diastolic function impairment, tested by transmitral blood pressure monitoring and TDI, was found in seven of 14 patients, all with reduced left ventricular contractility. CONCLUSIONS: We noticed a considerable variability of clinical presentation in our cases, according to the number of the ventricular segments affected by the anomaly. According to our data, middle-term prognosis appears to be better than that previously reported in the literature. We found a reduction of the systolic function only in 50% of cases, all with severe involvement of the apical and postero-lateral segments. Diastolic function was compromised only in those patients with severe impairment of systolic function. © 2007 Italian Federation of Cardiology

Pharmacokinetic behavior of Rituximab: a study of different schedules of administration for heterogeneous clinical settings.

This study was designed to report the pharmacokinetic behavior of Rituximab in patients affected with different diseases and treated with different schedules of administration. A low tumor burden was a common feature of all patients (N = 48) included in our study, whereas the timing of Rituximab administration varied from weekly (groups 1, 2, 3) to monthly (group 4). Group 1 included patients with follicular lymphoma treated with 4 weekly doses of Rituximab after first-line chemotherapy with CHOP. At the start of Rituximab, patients were in partial or complete clinical response but showed persistence of disease at molecular level (bcl-2–positive) in bone marrow and/or peripheral blood. Patients in group 2 had autoimmune disorders and Rituximab was given to act on B-cells, interfering with their production of autoantibodies. In patients with amyloidosis (group 3), Rituximab was given to kill progenitor B-cells of the small clone terminating in amyloid-producing plasma cells. In groups 2 and 3, the target of monoclonal antibody was a population of small B cells, which make an intrinsic feature of the diseases. Group 4 included patients with relapsed or refractory follicular and mantle cell lymphoma who underwent a salvage program of immunochemotherapy, purging in vivo and autotransplant: the first of the six planned doses of Rituximab was administered after a debulking phase with a third-generation regimen, such as VACOP-B. An enzyme-linked immunoassay (ELISA) developed and validated in our laboratory was used for the pharmacokinetic study. Rituximab disposition was characterized by a 2-exponential decay, with a long elimination half-life of approximately 3 weeks (range, 248–859 hours). The total systemic clearance ranged between 3.1 and 11.9 mL/hr/m2. After 4 weekly infusions, Rituximab concentration was ;2.5 mg/mL, which is approximately 85% of the steady-state level. Steady-state plasma concentrations of Rituximab were reached after 6 to 8 weekly infusions. The adopted pharmacokinetic model (2-compartment open model) seems to provide the best fit of Rituximab disposition both during and after treatment, even when different schedules of drug administration are used. Because several studies reported an association between response and serum Rituximab concentrations, a treatment based on a pharmacokinetic model may be useful for predicting the desired drug concentration

Pharmacokinetic Behavior of Rituximab: A Study of Different Schedules of Administration for Heterogeneous Clinical Settings

This study was designed to report the pharmacokinetic behavior of Rituximab in patients affected with different diseases and treated with different schedules of administration. A low tumor burden was a common feature of all patients (N=48) included in our study, whereas the timing of Rituximab administration varied from weekly (groups 1, 2, 3) to monthly (group 4). Group 1 included patients with follicular lymphoma treated with 4 weekly doses of Rituximab after first-line chemotherapy with CHOP. At the start of Rituximab, patients were in partial or complete clinical response but showed persistence of disease at molecular level (bcl-2-positive) in bone marrow and/or peripheral blood. Patients in group 2 had autoimmune disorders and Rituximab was given to act on B-cells, interfering with their production of autoantibodies. In patients with amyloidosis (group 3), Rituximab was given to kill progenitor B-cells of the small clone terminating in amyloid-producing plasma cells. In groups 2 and 3, the target of monoclonal antibody was a population of small B cells, which make an intrinsic feature of the diseases. Group 4 included patients with relapsed or refractory follicular and mantle cell lymphoma who underwent a salvage program of immunochemotherapy, purging in vivo and autotransplant: the first of the six planned doses of Rituximab was administered after a debulking phase with a third-generation regimen, such as VACOP-B. An enzyme-linked immunoassay (ELISA) developed and validated in our laboratory was used for the pharmacokinetic study. Rituximab disposition was characterized by a 2-exponential decay, with a long elimination half-life of approximately 3 weeks (range, 248-859 hours). The total systemic clearance ranged between 3.1 and 11.9 mL/hr/m. After 4 weekly infusions, Rituximab concentration was approximately 2.5 microg/mL, which is approximately 85% of the steady-state level. Steady-state plasma concentrations of Rituximab were reached after 6 to 8 weekly infusions. The adopted pharmacokinetic model (2-compartment open model) seems to provide the best fit of Rituximab disposition both during and after treatment, even when different schedules of drug administration are used. Because several studies reported an association between response and serum Rituximab concentrations, a treatment based on a pharmacokinetic model may be useful for predicting the desired drug concentration

Pharmacokinetic Behavior of Rituximab: A Study of Different Schedules of Administration for Heterogeneous Clinical Settings

This study was designed to report the pharmacokinetic behavior of Rituximab in patients affected with different diseases and treated with different schedules of administration. A low tumor burden was a common feature of all patients (N=48) included in our study, whereas the timing of Rituximab administration varied from weekly (groups 1, 2, 3) to monthly (group 4). Group 1 included patients with follicular lymphoma treated with 4 weekly doses of Rituximab after first-line chemotherapy with CHOP. At the start of Rituximab, patients were in partial or complete clinical response but showed persistence of disease at molecular level (bcl-2-positive) in bone marrow and/or peripheral blood. Patients in group 2 had autoimmune disorders and Rituximab was given to act on B-cells, interfering with their production of autoantibodies. In patients with amyloidosis (group 3), Rituximab was given to kill progenitor B-cells of the small clone terminating in amyloid-producing plasma cells. In groups 2 and 3, the target of monoclonal antibody was a population of small B cells, which make an intrinsic feature of the diseases. Group 4 included patients with relapsed or refractory follicular and mantle cell lymphoma who underwent a salvage program of immunochemotherapy, purging in vivo and autotransplant: the first of the six planned doses of Rituximab was administered after a debulking phase with a third-generation regimen, such as VACOP-B. An enzyme-linked immunoassay (ELISA) developed and validated in our laboratory was used for the pharmacokinetic study. Rituximab disposition was characterized by a 2-exponential decay, with a long elimination half-life of approximately 3 weeks (range, 248-859 hours). The total systemic clearance ranged between 3.1 and 11.9 mL/hr/m. After 4 weekly infusions, Rituximab concentration was approximately 2.5 microg/mL, which is approximately 85% of the steady-state level. Steady-state plasma concentrations of Rituximab were reached after 6 to 8 weekly infusions. The adopted pharmacokinetic model (2-compartment open model) seems to provide the best fit of Rituximab disposition both during and after treatment, even when different schedules of drug administration are used. Because several studies reported an association between response and serum Rituximab concentrations, a treatment based on a pharmacokinetic model may be useful for predicting the desired drug concentration

Rituximab (IDEC-C2B8): validation of a sensitive enzyme-linked immunoassay applied to a clinical pharmacokinetic study

Rituximab is a chimeric monoclonal antibody (MAb) directed against the B-cell CD20 antigen that has been approved for therapy of relapsed and resistant follicular. non-Hodgkin's lymphoma (NHL). This study describes the development and validation of a highly sensitive, rapid, accurate, precise enzyme-linked immunosorbent assay (ELISA) to measure Rituximab serum concentrations. This study also describes the application of the ELISA method to a pharmacokinetic study in a homogeneous group of patients with follicular lymphoma who received 4 weekly doses of MAb at the standard dose of 375 mg/m(2) as consolidation of chemotherapy. In the patients in this study, the median Rituximab serum concentrations increased during therapy, and showed a slow decline during the posttreatment period. The Rituximab elimination half-life of approximately 20 days accounts for the demonstrated accumulation of MAb in serum samples. Because previous pharmacokinetic studies showed a correlation between Rituximab serum levels and tumor response, the ELISA method used in this study, which allows a precise control of serum concentrations, could be useful for predicting the final response to the MAb and for selecting patients able to benefit from higher dosage or repeated drug administration