高三尖杉酯碱对鼻咽癌CNE-2Z细胞的增殖抑制和凋亡诱导作用

目的　探讨高三尖杉酯碱 (homoharringtonine,HHT)对鼻咽癌细胞CNE 2Z的增殖抑制和凋亡诱导作用。方法　采用MTT法检测增殖抑制率和IC50 ,流式细胞术、琼脂糖凝胶电泳和Hoechst 3 3 2 5 8/PI荧光染色分析细胞凋亡。结果　不同浓度的HHT分别处理CNE 2Z细胞 2 4、48和 72h ,抑制率随浓度的增加和时间的延长而增高 ,其IC50 分别为(0 62 9± 0 0 3 9)、(0 483± 0 0 2 7)、(0 3 89± 0 0 2 7)mg·L-1,各IC50 间差异有统计学意义 (P <0 0 1)。 1、0 5mg·L-1HHT处理细胞 8h ,流式细胞术观察到凋亡峰 ,荧光染色可见凋亡形态学改变 ,流式细胞术和荧光染色检出的凋亡率均高于对照组 (P <0 0 1) ;1mg·L-1HHT处理细胞 8h ,琼脂糖凝胶电泳可见DNA梯带。结论　HHT对CNE 2Z细胞具有增殖抑制作用 ,此抑制作用具有剂量和时间依赖性 ;HHT可诱导CNE 2Z细胞凋亡     

National mutation study among Danish patients with hereditary haemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominantly inherited vascular disease characterized by the presence of mucocutaneous telangiectasia and visceral arteriovenous malformations (AVM). The clinical diagnosis of HHT is based on the Curaçao criteria. About 85% of HHT patients carry mutations in the ENG, ACVRL1 or SMAD4 genes. Here, we report on the genetic heterogeneity in the Danish national HHT population and address the prevalence of pulmonary arteriovenous malformations (PAVM). Probands of 107 apparently unrelated families received genetic testing, including sequencing and multiplex ligation‐dependent probe amplification (MLPA) analyses of ENG, ACVRL1 and SMAD4. These 107 families included 320 patients confirmed to have HHT either clinically or genetically. In 89% of the probands (n = 95), a mutation was identified. We detected 64 unique mutations of which 27 (41%) were novel. Large deletions were identified in ENG and ACVRL1. The prevalence of PAVM was 52.3% in patients with an ENG mutation and 12.9% in the ACVRL1 mutation carriers. We diagnosed 80% of the patients clinically, fulfilling the Curaçao criteria, and those remaining were diagnosed by genetic testing. It is discussed when to assign pathogenicity to missense and splice site mutations. The adding of an extra criterion to the Curaçao criteria is suggested.     

Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study

Introduction

Epistaxis is the most frequent manifestation in hereditary hemorrhagic telangiectasia, in which no optimal treatment exists. It can lead to severe anemia and reduced quality of life. Positive effects of tranexamic acid, an antifibrinolytic drug, have been reported on epistaxis related to this disorder. We sought to evaluate the efficacy of treating nosebleeds in hereditary hemorrhagic telangiectasia with tranexamic acid.

Materials and Methods

In a randomized, double-blind, placebo controlled, cross-over phase IIIB study, 1 gram of tranexamic acid or placebo was given orally 3 times daily for 3 months for a total of 6 months.

Results

22 patients were included in the intention-to-treat analysis. Hemoglobin levels, the primary outcome measure, did not change significantly (p = 0.33). The secondary outcome measure was epistaxis score and patients reported a statistically significant reduction in nosebleeds, equaling a clinically relevant 54% diminution (p = 0.0031), as compared to the placebo period. No severe side effects were observed.

Conclusion

Tranexamic acid reduces epistaxis in patients with hereditary hemorrhagic telangiectasia.(Clinical trial registration numbers: BfArM 141 CHC 9008–001 and ClinicalTrials.gov NCT01031992)     

Hereditary hemorrhagic telangiectasia: How accurate are the clinical criteria?

The clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) is based on the Curaçao criteria. Three out of four criteria are required for a definite clinical diagnosis HHT, two criteria are considered “possible” HHT, and 0 or 1 criterion makes the diagnosis unlikely. However, these consensus diagnostic criteria have not been validated. We report on the diagnostic accuracy of the clinical criteria. A total of 450 consecutive persons ≥16 years of age were screened for HHT between May 2004 and September 2009, including a chest CT to screen for pulmonary arteriovenous malformations (AVMs). We selected 263 first‐degree relatives of disease‐causing mutation carriers who underwent mutation analysis. Genetic test results were considered the gold standard. The family mutation was present in 186 patients (mean age 42.9 ± 14.6 yr; 54.8% female). A clinical diagnosis was definite, “possible”, and unlikely in 168 (90.3%), 17 (9.1%), and 1 (0.5%) patient, respectively. In 77 persons the family mutation was absent (mean age 37.1 ± 12.3 yr, 59.7% female). In this group a clinical diagnosis was definite, possible, and unlikely in 0, 35 (45.5%), and 42 (54.5%) persons, respectively. The positive predictive value of a definite clinical diagnosis was 100% (95% CI 97.8–100), the negative predictive value of an unlikely diagnosis 97.7% (95% CI 87.9–99.6). Of 52 patients with “possible” HHT, 17 (32.7%) displayed an HHT‐causing mutation. The Curaçao clinical criteria have a good diagnostic performance. Genetic testing is particularly helpful in patients with a “possible” clinical diagnosis HHT. © 2013 Wiley Periodicals, Inc.     

基于PCA及SVM的运动想象脑电信号识别研究

为了解决脑机接口(BCI)中不同意识任务下运动想象脑电信号的分类问题,提出了一种基于PCA及SVM的识别方法。针对Hilbert-Huang变换和AR模型提取的脑电信号特征,首先采用主成分分析PCA对高维特征向量进行降维处理,然后用支持向量机进行分类。最后将本方法分类结果和Fisher线性分类、概率神经网络分类结果进行比较。实验结果表明,该方法分类正确率较高,复杂度低,具有一定的有效性,可用于脑机接口中。     

Hilbert-黄变换方法分析压力脉搏波信号

目的：将Hilbert-黄变换方法用于压力脉搏波信号的分析，以获得脉搏波信号的时域特征和频率-能量分布。方法：通过经验模态分解（EMD）将脉搏波分解为一组内在模态函数（IMF），对每个IMF进行Hilbert变换，获得脉搏波信号幅度和频率的时间分布；由HH谱得到边际谱，反映信号的能量一频率分布；对典型正常个体的脉搏波信号和该个体脉滑变时的脉搏波信号进行处理，比较两种状态下脉搏波信号时一频分布情况。结果：用于实验的两例信号的分析结果显示，脉平信号的HH边际谱与脉滑信号的HH边际谱所表现的能量-频率分布有明显区别，这种区别能被脉平和脉滑变时的心血管活动状态所解释。结论：EMD算法和HHT能较好地用于脉搏波的分析，并且在医学信号处理领域将会有广阔的应用前景。     

Hereditäre hämorrhagische Teleangiektasie

Zusammenfassung Die hereditäre hämorrhagische Teleangiektasie (HHT) ist eine autosomal-dominant vererbte Erkrankung des Gefäßbindegewebes. Pulmonale arteriovenöse und zerebral-vaskuläre Malformationen stellen Risikofaktoren für neurologische Komplikationen wie paradoxe Embolien und intrazerebrale Blutungen dar. Wir berichten von 2 Patientinnen, die an einer HHT mit pulmonalen arteriovenösen Malformationen erkrankt waren und paradox-embolische Insulte erlitten. Nach Coil-Embolisation der Fisteln kam es zu keinen weiteren zerebral-ischämischen Ereignissen. Bei ischämischen Insulten unklarer Ätiologie sollte an eine HHT als Ursache mit Behandlungsoption gedacht werden.     

Pulmonary arteriovenous malformations in children: outcomes of transcatheter embolotherapy

OBJECTIVE: To describe outcomes of transcatheter embolotherapy (TCE) in children with pulmonary arteriovenous malformations (PAVMs). STUDY DESIGN: Chart and imaging review of all children (age 相似文献   

人造机械瓣心音的分析研究

在一些致命性心脏病的诊断中,心音听诊是最有效也是应用得最成功的手段之一.鉴于目前机械瓣的使用非常普遍,研究简单有效的机械瓣病变判别方法对于临床诊断来讲具有重要意义.运用希尔波特-黄变换(HHT),针对不同的机械瓣心音进行分析,并设计一种基于Hilbert边界谱特征的提取方法,结合线性判别分析(LDA),对不同的机械瓣心音进行分类.同时,与基于局部最优基特征的分类器分类结果进行比较.分析结果表明,机械瓣心音的各阶Hilbert边界谱具有非常明显不同的分布,基于HHT的分类器识别率达到了97.3％,较基于局部最优基特征分类器的识别率(91.3％)更高.对于人造机械瓣心音而言,HHT是一种有效的分析处理手段.