Cerebrovascular atherosclerosis in type III hyperlipidemia is modulated by variation in the Apolipoprotein A5 gene

Objective

Type III Hyperlipoproteinemia is a rare lipid disorder with a frequency of 1-5 in 5000. It is characterized by the accumulation of triglyceride rich lipoproteins and patients are at increased risk of developping atherosclerosis. Type III HLP is strongly associated with the homozygous presence of the ε2 allele of the APOE gene.However only about 10% of subjects with APOE2/2 genotype develop hyperlipidemia and it is therefore assumed that further genetic and environmental factors are necessary for the expression of disease. It has recently been shown that variation in the APOA5 gene is one of these co-factors. The aim of this study is to investigate the development of cerebrovascular atherosclerosis in patients with Type III hyperlipoproteinemia (Type III HLP) and the role of variation in the APOA5 gene as a risk factor.

Methods

60 patients with type III hyperlipidemia and ApoE2/2 genotype were included in the study after informed consent. The presence of cerebrovascular atherosclerosis was investigated using B-mode ultra-sonography of the carotid artery. Serum lipid levels were measured by standard procedures. The APOE genotype and the 1131T > C and S19W SNPs in the APOA5 gene and the APOC3 sstI SNP were determined by restriction isotyping Allele frequencies were determined by gene counting and compared using Fisher''s exact test. Continuous variables were compared using the Mann Whitney test. A p value of 0.05 or below was considered statistically significant. Analysis was performed using Statistica 7 software.

Results

The incidence of the APOA5 SNPs, -1131T > C and S19W and the APOC3 sstI SNP were determined as a potential risk modifier. After correction for conventional risk factors, the C allele of the 1131T > C SNP in the APOA5 gene was associated with an increased risk for the development of carotid plaque in patients with Type III HLP with an odds ratio of 3.69. Evaluation of the genotype distribution was compatible with an independent effect of APOA5.

Conclusions

The development of atherosclerosis in patients with Type III HLP is modulated by variation in the APOA5 gene.     

Early detection of response to imatinib therapy for gastrointestinal stromal tumor by using 18F-FDG-positron emission tomography and computed tomography imaging

A 41-year old female with metastatic gastrointestinal stromal tumor was referred to 18F-FDG-positron emission tomography and computed tomography （PET/CT） scan before and after one-month treatment with imatinib （Glivec, Gleevec, Novartis, Basel, Switzerland）, a tyrosine kinase inhibitor （400 mg/d）. Metabolic response was evaluated before and after one month of therapy. The decrease of the maximum standardised uptake value （SUV） was 79% （from 9.8 to 2.1）. Positron emission tomography demonstrated complete metabolic response after one-month of imatinib treatment. Additionally, the previous lesion was compared with the coronal computerized tomographic image. There was no difference in the size of the tumor before and after therapy according to CT images. However, metabolic activity was inhibited. 18F-FDG-PEr is a valuable method for the detection of response to one-month imatinib treatment in patients with gastrointestinal stromal tumors.     

Combining deterministic and Monte Carlo calculations for fast estimation of scatter intensities in CT

A side effect of increased volume coverage by using multi-row and flat-panel detectors in computed tomography (CT) is the concurrently growing contribution of scattered radiation to the measured signal. In order to investigate the effect of scatter on x-ray projections used for CT imaging, our study aimed at the development of a simulation tool for fast calculation of primary and scatter intensities. We developed a deterministic method to assess the contribution of single-scatter events to the measured signal. The investigation of multiple scatter by Monte Carlo simulations showed that it results in a smooth signal as compared to single scatter. A hybrid method is proposed in order to optimize the performance of the scatter simulation: a fast and exact analytical calculation of the single-scatter intensity combined with a coarse Monte Carlo (MC) estimate of multiple scatter to reduce overall computational expenses, while assuring an acceptable signal quality. The results of the hybrid simulation of total scatter were in excellent agreement with the corresponding MC only simulations, thereby allowing us to reduce computational time by orders of magnitude. Estimates of two-dimensional scatter distributions for flat-panel CT imaging took about 30-40 s (per projection). The hybrid method provides a realistic simulation of x-ray scatter and offers a basis for scatter correction approaches.     

碳酸氢钠注射液的质量研究

目的：验证新生产的碳酸氢钠注射液是否符合质量标准、达到上市销售要求。方法：按照碳酸氢钠注射液的质量标注,进行一系列的质量研究。结果：碳酸氢钠注射液的各项指标均达到要求。结论：新生产的碳酸氢钠注射液符合质量标准,允许上市销售。