Mice with the R176Q cardiac ryanodine receptor mutation exhibit catecholamine-induced ventricular tachycardia and cardiomyopathy

Mutations in the cardiac ryanodine receptor 2 (RyR2) have been associated with catecholaminergic polymorphic ventricular tachycardia and a form of arrhythmogenic right ventricular dysplasia. To study the relationship between RyR2 function and these phenotypes, we developed knockin mice with the human disease-associated RyR2 mutation R176Q. Histologic analysis of hearts from RyR2(R176Q/+) mice revealed no evidence of fibrofatty infiltration or structural abnormalities characteristic of arrhythmogenic right ventricular dysplasia, but right ventricular end-diastolic volume was decreased in RyR2(R176Q/+) mice compared with controls, indicating subtle functional impairment due to the presence of a single mutant allele. Ventricular tachycardia (VT) was observed after caffeine and epinephrine injection in RyR2(R176Q/+), but not in WT, mice. Intracardiac electrophysiology studies with programmed stimulation also elicited VT in RyR2(R176Q/+) mice. Isoproterenol administration during programmed stimulation increased both the number and duration of VT episodes in RyR2(R176Q/+) mice, but not in controls. Isolated cardiomyocytes from RyR2(R176Q/+) mice exhibited a higher incidence of spontaneous Ca(2+) oscillations in the absence and presence of isoproterenol compared with controls. Our results suggest that the R176Q mutation in RyR2 predisposes the heart to catecholamine-induced oscillatory calcium-release events that trigger a calcium-dependent ventricular arrhythmia.     

Worsening renal function is not associated with response to treatment in acute heart failure

Background

About a fourth of acute decompensated heart failure (ADHF) patients develop renal dysfunction during their admission. To date, the association of ADHF treatment with the development of worsening renal function (WRF) remains contentious. Thus, we examined the association of WRF with changes in BNP levels and with mortality.

Methods

We performed retrospective chart review of patients admitted with ADHF who had BNP, eGFR, creatinine and blood urea nitrogen (BUN) values measured both on admission and discharge. Survival analysis was conducted using Cox proportional hazards model and correlation was measured using Spearman's rank correlation test.

Results

358 patients admitted for ADHF were evaluated. WRF was defined as > 20% reduction in eGFR from admission to discharge and response to treatment was assessed by ΔBNP. There was a statistically significant reduction in BNP and increase in BUN during the admission. ΔBNP did not correlate with either ΔGFR or ΔBUN. Patients who developed WRF and those who did not, had a similar reduction in BNP. On univariate survival analysis, ΔBUN, but not ΔeGFR, was associated with 1-year mortality. In multivariate Cox proportional hazards model, BUN at discharge was associated with 1-year mortality (HR: 1.02, p < 0.001), but ΔeGFR and ΔBUN were not associated with the primary endpoint.

Conclusion

During ADHF treatment, ΔBNP was not associated with changes in renal function. Development of WRF during ADHF treatment was not associated with mortality. Our study suggests that development of WRF should not preclude diuresis in ADHF patients in the absence of volume depletion.     

腹部巨大囊性病变CT分析

1临床资料 腹部巨大囊性病变（最小径线10cm以上者）28（男16,女12）例,年龄0.5～83（平均44.6）岁,腹痛14例,腹胀10例,腰痛9例,发热2例,病程1mo至10数年。良性26例：卵巢囊肿4例,卵巢囊腺瘤2例,肾囊肿2例,肾重度积水3例,输尿管囊肿2例,胰腺及脾脏囊肿各3例。     

乙型肝炎肝组织血管病变组织及免疫组织化学的研究

乙型肝炎(HB)已成为我国危害最大的社会公共卫生问题.近年来,我们在分析、研究国内外有关病毒性肝炎文献后选择了以HB患者肝组织活检观察为主的研究方法,从肝组织学随访中研究各型HB肝实质变性坏死及肝纤维组织增生的动态变化规律[1-8],采用组织化学(组化)及免疫组织化学(免疫组化)染色方法对肝组织内HBsAg,HBcAg表达[3],不同类型纤维组织增生情况,血清HBeAg与抗-HBe转换及透明质酸,色氨酸代谢变化[9-13],进行了深入研究.     

伽玛刀联合长春瑞滨、顺铂治疗局部晚期肺癌疗效观察简

目的：探讨体部伽玛刀联合长春瑞滨、顺铂治疗局部晚期非小细胞肺癌的临床疗效及不良反应。方法：自2008年1月-2010年7月,对101例非小细胞肺癌患者按治疗方法分为伽玛刀联合长春瑞滨、顺铂（联合组）52例和单纯应用长春瑞滨、顺铂（对照组）49例,比较两组治疗后的近期疗效、生存期及不良反应。结果：联合组、对照组有效率分别为82．69％和53．06％,两组1年生存率分别为69．23％,42．86％。联合组的急性放射性肺损伤发生率11．54％,急性放射性食管损伤发生率9．62％,均为1—2度。两组的血液毒性主要表现为白细胞下降,另外还合并有恶心、呕吐等,联合组发生几率明显高于对照组,但经过对症治疗均能顺利完成治疗。结论：伽玛刀联合长春瑞滨、顺铂治疗能显著提高局部晚期肺癌患者的近期疗效、生存时间;白细胞下降、恶心、呕吐等不良反应较单纯化疗组也明显增加,有部分患者还会出现急性放射性肺损伤,急性放射性食管损伤,但经过对症处理基本恢复正常不影响治疗。     

麦冬类中药组织切片计算机三维重建图鉴

利用计算机技术实现麦冬类中药组织连续切片三维重建与动态显示,为计算机辅助生药学鉴定和教学提供了新的三维图像技术和研究资料。     

女性缩阴术30例临床分析

1 临床资料 2000-03/2004-06阴道松弛症女性30例,年龄24～44岁,其中24～30岁12例,占40%;31～40岁10例,占33.3%;41～44岁8例,占26.7%.术前检查阴道容三指以上,自诉因阴道松弛性生活时快感不足,均排除子宫脱垂、阴道炎及阴道肿瘤等疾病.手术在月经完全干净3 d后,采用硬膜外麻醉或局部麻醉下进行.患者取膀胱截石位,于阴道口外6点处设计出一弧形切口,左右宽度3～7 cm具体视阴道松弛程度而定,沿设计线在阴道黏膜下注射盐酸肾上腺素盐水以利止血和分离,切开并剥离阴道后壁黏膜,暴露黏膜下肌肉,以可吸收缝线拉拢缝合阴道黏膜下左右侧阴道括约肌及肛提肌等,从阴道深处开始缝合,缝到阴道口附近处.缝合后阴道容二指松.阴道后壁黏膜不切除,阴道黏膜下肌肉左右对叠缝合后阴道黏膜自然向上膨隆形成一皱襞.阴道外的横弧形切口因黏膜下肌肉左右拉拢缝合,变成竖形切口以丝线间断缝合.术后静滴抗生素3 d,每天以碘伏清洗切口1次,7 d拆线,2 mo内禁止性生活.术后随访3～6 mo,自诉性快感明显增强22例,改善8例.     

Targeting ryanodine receptors for anti-arrhythmic therapy

Antiarrhythmic drugs are a group of pharmaceuticals that suppress or prevent abnormal heart rhythms, which are often associated with substantial morbidity and mortality. Current antiarrhythmic drugs that typically target plasma membrane ion channels have limited clinical success and in some cases have been described as being pro-arrhythmic. However, recent studies suggest that pathological release of calcium (Ca(2+)) from the sarcoplasmic reticulum via cardiac ryanodine receptors (RyR2) could represent a promising target for antiarrhythmic therapy. Diastolic SR Ca(2+) release has been linked to arrhythmogenesis in both the inherited arrhythmia syndrome 'catecholaminergic polymorphic ventricular tachycardia' and acquired forms of heart disease (eg, atrial fibrillation, heart failure). Several classes of pharmaceuticals have been shown to reduce abnormal RyR2 activity and may confer protection against triggered arrhythmias through reduction of SR Ca(2+) leak. In this review, we will evaluate the current pharmacological methods for stabilizing RyR2 and suggest treatment modalities based on current evidence of molecular mechanisms.