Treatment of patients with aortic atherosclerotic disease with paclitaxel-associated lipid nanoparticles

OBJECTIVE: The toxicity of anti-cancer chemotherapeutic agents can be reduced by associating these compounds, such as the anti-proliferative agent paclitaxel, with a cholesterol-rich nanoemulsion (LDE) that mimics the lipid composition of low-density lipoprotein (LDL). When injected into circulation, the LDE concentrates the carried drugs in neoplastic tissues and atherosclerotic lesions. In rabbits, atherosclerotic lesion size was reduced by 65% following LDE-paclitaxel treatment. The current study aimed to test the effectiveness of LDE-paclitaxel on inpatients with aortic atherosclerosis. METHODS: This study tested a 175 mg/m2 body surface area dose of LDE-paclitaxel (intravenous administration, 3/3 weeks for 6 cycles) in patients with aortic atherosclerosis who were aged between 69 and 86 yrs. A control group of 9 untreated patients with aortic atherosclerosis (72-83 yrs) was also observed. RESULTS: The LDE-paclitaxel treatment elicited no important clinical or laboratory toxicities. Images were acquired via multiple detector computer tomography angiography (64-slice scanner) before treatment and at 1-2 months after treatment. The images showed that the mean plaque volume in the aortic artery wall was reduced in 4 of the 8 patients, while in 3 patients it remained unchanged and in one patient it increased. In the control group, images were acquired twice with an interval of 6-8 months. None of the patients in this group exhibited a reduction in plaque volume; in contrast, the plaque volume increased in three patients and remained stable in four patients. During the study period, one death unrelated to the treatment occurred in the LDE-paclitaxel group and one death occurred in the control group. CONCLUSION: Treatment with LDE-paclitaxel was tolerated by patients with cardiovascular disease and showed the potential to reduce atherosclerotic lesion size

A Systematic review for sudden cardiac death in hypertrophic cardiomyopathy patients with Myocardial Fibrosis: A CMR LGE Study

Background: Hypertrophic cardiomyopathy (HCM) patients have a predisposition for malignant VT/VF and consequently, sudden cardiac death (SCD). In single center studies, late gadolinium enhancement (LGE) defined fibrosis has been linked to VT/VF. However, despite innumerable investigations, SCD has not been definitely attributable to LGE. Explanations for these are believed to be related to insufficient statistical power. Methods: We performed an electronic search of MEDLINE, PubMed: and CMR abstracts for original data published or presented between Jan 2001 to Mar 2011. Key search terms: HCM, LV fibrosis, SCD and LGE. Studies were screened for eligibility based on inclusion criteria: referral for CMR exam with LGE for HCM; and follow-up for incidence of VT/VF and SCD. Categorical variables were evaluated between patient groups via Chi-square test. Results: A total of 64 studies were initially identified. Of these, 4 (6.3%) were identified and included (n = 1063 patients). Three prospective and one retrospective study were included. LGE was detected in 59.6% of patients. As expected, the presence of myocardial fibrosis was associated with VT/VF (x2 = 6.5, p < 0.05; OR 9.0, (95% CI 1.2 to 68.7). Moreover, myocardial fibrosis strongly predicted SCD (x2 = 6.6, p < 0.05; OR 3.3 (95% CI 1.2 to 9.7). Conclusion: Despite single center CMR studies, LGE has consistently predicted VT/VF while prediction of SCD has remained paradoxically unlinked. Although the lack of studies meeting our criteria limited our ability to perform a comprehensive meta-analysis, we have been able to demonstrate for the first time that LGE-defined fibrosis is a predictor of SCD in patients with HCM0

Treatment of patients with aortic atherosclerotic disease with paclitaxel-associated lipid nanoparticles

OBJECTIVE: The toxicity of anti-cancer chemotherapeutic agents can be reduced by associating these compounds, such as the anti-proliferative agent paclitaxel, with a cholesterol-rich nanoemulsion (LDE) that mimics the lipid composition of low-density lipoprotein (LDL). When injected into circulation, the LDE concentrates the carried drugs in neoplastic tissues and atherosclerotic lesions. In rabbits, atherosclerotic lesion size was reduced by 65% following LDE-paclitaxel treatment. The current study aimed to test the effectiveness of LDE-paclitaxel on inpatients with aortic atherosclerosis. METHODS: This study tested a 175 mg/m2 body surface area dose of LDE-paclitaxel (intravenous administration, 3/3 weeks for 6 cycles) in patients with aortic atherosclerosis who were aged between 69 and 86 yrs. A control group of 9 untreated patients with aortic atherosclerosis (72-83 yrs) was also observed. RESULTS: The LDE-paclitaxel treatment elicited no important clinical or laboratory toxicities. Images were acquired via multiple detector computer tomography angiography (64-slice scanner) before treatment and at 1-2 months after treatment. The images showed that the mean plaque volume in the aortic artery wall was reduced in 4 of the 8 patients, while in 3 patients it remained unchanged and in one patient it increased. In the control group, images were acquired twice with an interval of 6-8 months. None of the patients in this group exhibited a reduction in plaque volume; in contrast, the plaque volume increased in three patients and remained stable in four patients. During the study period, one death unrelated to the treatment occurred in the LDE-paclitaxel group and one death occurred in the control group. CONCLUSION: Treatment with LDE-paclitaxel was tolerated by patients with cardiovascular disease and showed the potential to reduce atherosclerotic lesion size

PRISM (Polarized Radiation Imaging and Spectroscopy Mission): an extended white paper

Contains fulltext : 126057.pdf (preprint version ) (Open Access

Belle II SVD ladder assembly procedure and electrical qualification

The Belle II experiment at the SuperKEKB asymmetric collider in Japan will operate at a luminosity approximately 50 times larger than its predecessor (Belle). At its heart lies a six-layer vertex detector comprising two layers of pixelated silicon detectors (PXD) and four layers of double-sided silicon microstrip detectors (SVD). One of the key measurements for Belle II is time-dependent CP violation asymmetry, which hinges on a precise charged-track vertex determination. Towards this goal, a proper assembly of the SVD components with precise alignment ought to be performed and the geometrical tolerances should be checked to fall within the design limits. We present an overview of the assembly procedure that is being followed, which includes the precision gluing of the SVD module components, wire-bonding of the various electrical components, and precision three dimensional coordinate measurements of the jigs used in assembly as well as of the final SVD modules

Belle II silicon vertex detector

The Belle II experiment at the SuperKEKB collider in Japan is designed to indirectly probe new physics using approximately 50 times the data recorded by its predecessor. An accurate determination of the decay-point position of subatomic particles such as beauty and charm hadrons as well as a precise measurement of low-momentum charged particles will play a key role in this pursuit. These will be accomplished by an inner tracking device comprising two layers of pixelated silicon detector and four layers of silicon vertex detector based on double-sided microstrip sensors. We describe herein the design, prototyping and construction efforts of the Belle-II silicon vertex detector

EMC studies for the vertex detector of the Belle II experiment

The upgrade of the Belle II experiment plans to use a vertex detector based on two different technologies, DEPFET pixel (PXD) technology and double side silicon microstrip (SVD) technology. The vertex electronics are characterized by the topology of SVD bias that forces to design a sophisticated grounding because of the floating power scheme. The complex topology of the PXD power cable bundle may introduce some noise inside the vertex area. This paper presents a general overview of the EMC issues present in the vertex system, based on EMC tests on an SVD prototype and a study of noise propagation in the PXD cable bundle based on Multi-conductor transmission line theory