A retrospective study of patients with the hereditary syndrome of congenital cataract,mitochondrial myopathy of heart and skeletal muscle and lactic acidosis

The objectives of this study were to describe the course of two forms of an hereditary syndrome characterised by congenital cataract, mitochondrial myopathy of heart and skeletal muscle and lactic acidosis. We also sought to determine clinical, physicochemical and histopathological data which might allow early distinction between the two forms. We compared the ages at which clinical and physicochemical signs appeared in 16 patients. In 5 patients, enzyme-histochemical and ultrastructural data of skeletal muscle were available and muscle fibre composition analysed morphometrically. In any particular family only one form of the syndrome occurred. Amongst the patients who did not survive (range 14–34 years) 4 patients died in the neonatal period and 7 died at a median age of 23 years. The median age of the survivors was 19 years (range 15–42 years). Outflow obstruction of the left ventricle was noted in four deceased patients at variable times prior to death. The other deceased patients were not examined, but the cause of death was invariably heart failure. In none of the surviving patients was outflow obstruction noted. Enzyme-histochemical and ultrastructural findings were not specific for the course of the disease. In one biopsy, taken at the age of 3.5 months from a patient who survived, strong lipid accumulation was noted. Morphometric analysis showed proliferation of the mitochondria in muscle fibres, which increased during the course of the disease.     

A comparison of ultrastructural changes on endomyocardial biopsy specimens obtained from patients with diabetes mellitus with and without hypertension

Summary The pathogenesis of diabetic cardiomyopathy is unknown. The synergistic, or enhanced, effect of hypertension on pathological changes in the heart of diabetic patients has been highly suspected. The purpose of this study was to evaluate the myocardial changes related to diabetes mellitus with and without hypertension, using biopsy specimens. We examined the ultrastructural changes in biopsy specimens of the endomyocardium obtained from 25 patients. They were divided into four groups: controls without hypertension or diabetes mellitus (n=6), and patient with hypertension (n=3), diabetes mellitus (n=8), and diabetes with hypertension (n=8). The diabetic patients showed nearly normal or mildly depressed systolic left ventricular function. Ultrastructural pictures were analyzed for thickening of the capillary basement membrane, presence of toluidine blue-positive materials (i.e., materials showing metachromasia) in the myocytes, size of myocytes, and interstitial fibrosis. The thickening of the capillary basement membrane, the accumulation of toluidine blue-positive materials, and interstitial fibrosis were all significantly greater in the patients with diabetes mellitus compared to the control subjects. The myocytes tended to be small (cell atrophy) in the diabetes group. Although these pathological changes in the heart were characteristic of diabetic patients, irrespective of the presence or absence of hypertension, the presence of hypertension increased the pathological changes of myocardial cells as well as abnormality in the capillary vessels in patients with diabetes mellitus. Alterations in the myocardial cells and capillaries, caused by diabetes mellitus, may lead to myocardial cell injury and interstitial fibrosis and, ultimately, to ventricular systolic and diastolic dysfunction, especially when the diabetes is accompanied by hypertension.     

急性心肌梗塞错误溶栓治疗12例分析

自1993年12月至1995年8月，对155例急性心肌梗塞（AMI）病人进行溶栓治疗，12例发生误溶(7．7％）。其中早期复极综合征4例，室壁瘤2例，心肌炎1例，心肌病1例，完全性左束支阻滞1例，间歇性左前分支阻滞互例，其它2例。本文分析了误溶病例与AMI的鉴别要点，并提出了减少误溶，提高诊疗水平的措施。     

中国肥厚型心肌病患者血栓栓塞事件风险预测模型的构建研究

背景 血栓栓塞（TE）事件是肥厚型心肌病（HCM）的重要并发症。目前针对HCM患者TE事件的风险预测,仅国外学者构建了两个模型：HCM Risk-CVA及French HCM score,然而,现有研究发现HCM Risk-CVA模型对于中国HCM患者的临床价值较为有限。目的 本研究拟构建适合中国HCM患者的TE事件风险预测模型。方法本研究系回顾性队列研究,收集2010—2018年在四川大学华西医院就诊的537例HCM患者的病例资料。本研究通过电话随访或电子病历系统查询患者就诊记录,每6～12个月随访1次,直至出现终点事件或死亡或研究拟定的评估日期（2019-12-31）,终点事件定义为复合性TE事件。采用单因素和多因素Cox回归分析构建风险预测模型,并使用自助重抽样的方法进行内部验证。结果 537例患者中,24例患者有不同程度的数据缺失,最终纳入513例患者。中位随访时间为4.2(1.3,6.2)年,随访过程中42例（8.18%）发生TE事件,年发病率为2.10%[95%CI(1.47%,2.73%)]。根据多因素Cox回归模型构建TE事件风险预测模型,最终纳入年龄、既往TE事件、心...     

2型糖尿病对扩张型心肌病患者预后的影响研究

背景 2型糖尿病可增加患者心血管疾病的早发风险,对健康构成重大威胁。阐明2型糖尿病对扩张型心肌病患者预后的影响,有利于指导患者的管理。目的 探讨2型糖尿病对扩张型心肌病患者预后的影响。方法 回顾性选取广西医科大学第一附属医院心血管内科2015年1月至2020年5月收治的313例扩张型心肌病患者为研究对象。根据患者是否罹患2型糖尿病将患者分为糖尿病组（n=66）和非糖尿病组（n=247）,收集患者一般资料、实验室检查指标并进行随访,随访终点事件为全因死亡,随访日期截至2021-12-31。采用landmark比较两组患者的生存率。建立多因素Cox比例风险回归模型,探究扩张型心肌病患者全因死亡的影响因素。结果 Landmark分析结果显示,糖尿病组和非糖尿病组扩张型心肌病患者随访1年内的生存率比较,差异无统计学意义（χ2=1.520,P=0.218）;随访1年后,糖尿病组扩张型心肌病患者的生存率低于非糖尿病组（χ2=4.414,P=0.036）。分段拟合法构建的多因素Cox比例风险回归分析显示,收缩压[HR=0.965,95%CI(0.948,0.982)]、N末端B型利钠肽原[HR=9....     

Progressive dilated cardiomyopathy in a patient with longstanding and complete prednisone-induced hematological remission of idiopathic hypereosinophilic syndrome

Summary A female patient is described in whom the diagnosis of idiopathic hypereosinophilic syndrome (HES) with heart disease and peripheral neuropathy was made at the age of 32 years. Although prednisone induced a prompt and longstanding complete hematological remission, progressive and eventually intractable heart failure developed, and the patient died 6 years later. Endomyocardial biopsy at diagnosis showed infiltration with intact and disintegrated eosinophils and Charcot-Leyden crystals. Echocardiographic follow-up (including Doppler-Echocardiography) revealed mitral regurgitation with thickening and impaired motility of the posterior mitral leaflet, as well as progressive dilated cardiomyopathy. At autopsy, a diffuse interstitial fibrosis with patchy prominence in an eccentric hypertrophic and highly dilated heart was found. There were no significant endocardial thickening and no mural thrombi. In contrast to the findings of the initial endomyocardial biopsy, autopsy revealed no eosinophilic infiltrate.In this case, eosinophil-induced heart disease manifested as dilated cardiomyopathy, without endocardial fibrosis as originally described by Löffler. We speculate, that eosinophils have been deposited predominantly in the myocard at an early stage of disease, and — activated locally — secreted their granule proteins producing an initial damage to capillary endothelial cells and myocytes. After prednisone-induced clearance of eosinophils from blood and tissues, progressive, self-perpetuating interstitial fibrosis of the myocard and loss of myocytes eventually resulted in end-stage dilated cardiomyopathy.Abkürzungsverzeichnis HES idiopathic hypereosinophilic syndrome - UBBC unsaturated vitamin B₁₂ binding capacity - ECP eosinophil cationic protein - MBC major basic protein - EDD end-diastolic diameter of the left ventricle - LA left atrium diameter - LVEDP left ventricular end-diastolic pressure - NIH National Institutes of Health     

Effective and safe therapy with coenzyme Q10 for cardiomyopathy

Summary Coenzyme Q₁₀ (CoQ₁₀) is indispensable in mitochondrial bioenergetics and for human life to exist. 88/115 patients completed a trial of therapy with CoQ₁₀ for cardiomyopathy. Patients were selected on the basis of clinical criteria,X-rays, electrocardiograms, echocardiography, and coronary angiography. Responses were monitored by ejection fractions, cardiac output, and improvements in functional classifications (NYHA). Of the 88 patients 75%–85% showed statistically significant increases in two monitored cardiac parameters. Patients with the lowest ejection fractions (approx. 10%–30%) showed the highest increases (115%–210%) and those with higher ejection fractions (50%–80%) showed increases of approx. 10%–25% on therapy. By functional classification, 17/21 in class IV, 52/62 in class III, and 4/5 in class II improved to lower classes. Clinical responses appeared over variable times, and are presumably based on mechanisms of DNA-RNA-protein synthesis of apoenzymes which restore levels of CoQ₁₀ enzymes in a deficiency state. 10/21 (48%) of patients in class IV, 26/62 (42%) in class III, and 2/5 (40%) in class II had exceptionally low control blood levels of CoQ₁₀. Clinical responses on therapy with CoQ₁₀ appear maximal with blood levels of approx. 2.5 µg CoQ₁₀/ml and higher during therapy.Abbreviations CHF Congestive heart failure - CO Cardiac output - CoQ₁₀ Coenzyme Q₁₀ - EF Ejection fraction - IC Impedance cardiography - NYHA New York Heart Association - STI Systolic time interval     

Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside

Genetic defects of the dystrophin-glycoprotein complex (DGC) cause hereditary dilated cardiomyopathy. Enteroviruses can also cause cardiomyopathy and we have previously described a mechanism involved in enterovirus-induced dilated cardiomyopathy: The enteroviral protease 2A directly cleaves dystrophin in the hinge 3 region, leading to functional dystrophin impairment. During infection of mice with coxsackievirus B3, the DGC in the heart is disrupted and the sarcolemmal integrity is lost in virus-infected cardiomyocytes. Additionally, dystrophin deficiency markedly increases enterovirus-induced cardiomyopathy in vivo, suggesting a pathogenetic role of the dystrophin cleavage in enterovirus-induced cardiomyopathy. Here, we extend these experimental findings to a patient with dilated cardiomyopathy due to a coxsackievirus B2 myocarditis. Endomyocardial biopsy specimens showed an inflammatory infiltrate and myocytolysis. Immunostaining for the enteroviral capsid antigen VP1 revealed virus-infected cardiomyocytes. Focal areas of cardiomyocytes displayed a loss of the sarcolemmal staining pattern for dystrophin and -sarcoglycan identical to previous findings in virus-infected mouse hearts. In vitro, coxsackievirus B2 protease 2A cleaved human dystrophin. These findings demonstrate that in human coxsackievirus B myocarditis a focal disruption of the DGC can principally occur and may contribute to the pathogenesis of human enterovirus-induced dilated cardiomyopathy.     

A girl with 1p36 deletion syndrome and congenital fiber type disproportion myopathy

Chromosome 1p36 deletion syndrome is characterized by hypotonia, moderate to severe developmental and growth retardation, and characteristic craniofacial dysmorphism. Muscle hypotonia and delayed motor development are almost constant features of the syndrome. We report a 4-year-old Japanese girl with 1p36 deletion syndrome whose muscle pathology showed congenital fiber type disproportion (CFTD) myopathy. This is the first case report of 1p36 deletion associated with CFTD. This association may indicate that one of the CFTD loci is located at 1p36. Ski proto-oncogene −/− mice have phenotypes that resemble some of the features observed in patients with 1p36 deletion syndrome. Because fluorescent in situ hybridization analysis revealed that the human SKI gene is deleted in our patient, some genes in 1p36, including SKI proto-oncogene, may be involved in muscle hypotonia and delayed motor development in this syndrome. Received: March 4, 2002 / Accepted: July 7, 2002     

骨髓间充质干细胞分化为血管内皮细胞的实验研究

目的 :探讨骨髓间充质干细胞 (MSCs)自体移植后在扩张型心肌病(DCM)微环境中分化为血管内皮细胞的可行性。方法 :以日本大耳白兔为研究对象 ,分离培养扩增MSCs,盐酸阿霉素耳缘静脉注射复制兔DCM模型 ,将 5溴脱氧尿嘧啶 (BrdU)标记的MSCs移植到DCM心肌内 ,4周后观察移植细胞的增殖分化情况。结果 :细胞移植 4周后 ,实验组心肌内有BrdU标记的阳性细胞 ,有一部分参与组成新生血管 ,对照组中没有发现 ,且实验组毛细血管密度大于对照组 ,差异具有显著性 (P<0 .0 1)。结论 :MSCs自体移植到扩张型心肌病后可以分化为血管内皮细胞。