Cardiomyopathy in congenital complete lipodystrophy

Molecular genetic studies have pointed to a relationship between congenital lipodystrophy syndromes and some cardiac disorders. For instance, mutations in LMNA cause either lipodystrophy or cardiomyopathy, indicating that different mutations in the same gene can produce these clinical syndromes. The present authors describe a 10-year-old female with Berardinelli-Seip congenital complete lipodystrophy (MIM 606158) caused by homozygosity for a frameshift mutation in BSCL2. In addition to the typical attributes of complete lipodystrophy, this subject had hypertrophic cardiomyopathy diagnosed in the first year of her life; its progress has been followed with non-invasive imaging. The mechanism underlying the hypertrophic cardiomyopathy in complete lipodystrophy is unclear. It may result from a direct effect of the mutant gene or it might be secondary to the effects of hyperinsulinemia on cardiac development. The variability of the associated cardiomyopathy in patients with complete generalized lipodystrophy may be caused by differential effects of mutations in the same gene or of mutations in different genes which underlie the lipodystrophy phenotype.     

经皮腔内室间隔心肌消融术对心电指标的影响

目的研究肥厚梗阻型心肌病患者经皮腔内室间隔心肌消融术对心电指标的影响。方法对50例肥厚梗阻型心肌病患者行经皮腔内室间隔心肌消融术,记录术前、术中和术后出现的心律失常类型,配对分析术前、术后心电指标的变化。结果术后与术前相比,QRS时限[(122.0±24.0)ms对(97.3±15.5)ms,P=0.000]明显延长,QTc[(469.3±32.2)ms对(434.3±41.5)ms,P=0.004]、PR间期[(169±26)ms对(162±24)ms,P=0.044]稍延长。术中心律失常发生率分别为:右束支传导阻滞70%(35/50),左束支传导阻滞8%(4/50),一过性AVB38%(19/50),频发室性早搏24%(12/50),短阵室性心动过速24%(12/50);未发生持续性室性心动过速和室颤。术后心律失常发生率分别为:右束支传导阻滞56%(28/50),左束支传导阻滞8%(4/50),交界区性心动过速4%(2/50),频发室性早搏16%(8/50),短阵室性心动过速8%(4/50)。无永久性起搏器植入及死亡病例。结论经皮腔内室间隔心肌消融术致心律失常的发生率高,右束支传导阻滞最为常见。严格选择适应证后谨慎地行PTSMA术是安全、可行的。     

Anti-mitochondrial antibodies (anti-M7) in heart diseases recognize epitopes on bacterial and mammalian sarcosine dehydrogenase.

The anti-mitochondrial antibody (AMA) anti-M7 has been shown to occur exclusively in sera from patients with acute and chronic myocarditis. Applying different enzymes of the inner mitochondrial membrane to ELISA, anti-M7-positive sera reacted only with sarcosine dehydrogenase (SD) from Pseudomonas aeruginosa. Testing these sera in the Western blot against a commercially available SD as well as against SD prepared from rat liver mitochondria, a determinant at 42 kD and 90 kD, respectively, was visualized. Using submitochondrial particles (SMP) from bovine heart and rat liver another major determinant at 64 kD could be observed with both antigen fractions. Liver SMP also expressed the SD-related, 90-kD epitope. Sera from patients with other AMA-positive and AMA-negative autoimmune diseases were negative with these different determinants. The identity of the 64-kD epitope on heart and liver SMP as well as the 42-kD polypeptide of bacterial SD and the 90-kD epitope on mammalian SD was proven by absorption studies and by elution of antibodies from the antigen bound to the immobilon sheets after immunoblotting. The SD enzyme activity was not affected by anti-64-kD and anti-42-kD antibodies in vitro. It is concluded that anti-M7 antibodies may be stimulated by an antigen expressed on cardiocytes during an infection which shares epitopes with SD, an evolutionary highly conserved protein. SD-sensitized B cell clones could therefore be triggered by the M7-antigen which shows homology to SD.     

The haplotype block, NFKBIL1-ATP6V1G2-BAT1-MICB-MICA, within the class III-class I boundary region of the human major histocompatibility complex may control susceptibility to hepatitis C virus-associated dilated cardiomyopathy

Cardiomyopathy is a heart muscle disease with impaired stretch response that can result in severe heart failure and sudden death. A small proportion of hepatitis C virus (HCV)-infected patients may be predisposed to develop dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). The molecular mechanisms involved in the predisposition remain unknown due in part to the lack of information on their genetic background. Because the human leukocyte antigen (HLA) region has a pivotal role in controlling the susceptibility to HCV-induced liver disease, we hypothesized that particular HLA alleles and/or non-HLA gene alleles within the human major histocompatibility complex (MHC) genomic region might control the predisposition to HCV-associated DCM (HCV-DCM) and/or HCV-associated HCM (HCV-HCM). Here, we present mapping results of the MHC-related susceptibility gene locus for HCV-associated cardiomyopathy by analyzing microsatellite and single nucleotide polymorphism markers. To delineate the susceptibility locus, we genotyped 44 polymorphic markers scattered across the entire MHC region in a total of 59 patients (21 HCV-DCM and 38 HCV-HCM) and 120 controls. We mapped HCV-DCM susceptibility to a non-HLA gene locus spanning from NFKBIL1 to MICA gene loci within the MHC class III-class I boundary region. Our results showed that HCV-DCM was more strongly associated with alleles of the non-HLA genes rather than the HLA genes themselves. In addition, no significant association was found between the MHC markers and HCV-HCM. This marked difference in the MHC-related disease susceptibility for HCV- associated cardiomyopathy strongly suggests that the development of HCV- DCM and HCV-HCM is under the control of different pathogenic mechanisms.     

Pathological analysis of hypertrophic cardiomyopathy simulating dilated cardiomyopathy

The pathomorphologic features of hypertrophic cardiomyopathy simulating dilated cardiomyopathy in the late stage (HCM-DCM) were compared with those of ordinary hypertrophic cardiomyopathy (HCM). Seven autopsied hearts with HCM-DCM and 11 with HCM were assessed quantitatively using an image analyzer. Unlike HCM, significant left ventricular enlargement and wall thinning were observed in HCM-DCM, and the percentage areas of massive fibrosis and disarray were significantly greater. In HCM-DCM, the disarray was distributed diffusely, whereas massive fibrosis was distributed more intensively in the ventricular septum and anterior wall than in the lateral and posterior wall. Narrowing of intramyocardial small arteries was observed more frequently in HCM-DCM, especially in the ventricular septum and anterior wall, than in HCM. These results suggest that the enlargement and wall thinning of the left ventricle in HCM-DCM are attributable to non-uniform progression of massive fibrosis, which is closely related to small-arterial lesions.     

Anti-mitochondrial flavoprotein autoantibodies of patients with myocarditis and dilated cardiomyopathy (anti-M7): interaction with flavin-carrying proteins, effect of vitamin B2 and epitope mapping

Vitamin B2 and flavin cofactors are transported tightly bound to immunoglobulin in human serum. We reasoned that anti-mitochondrial flavoprotein autoantibodies (alpha Fp-AB) present in the serum of patients with myocarditis and cardiomyopathy of unknown aetiology may form immunoglobulin aggregates with these serum proteins. However, immunodiffusion and Western blot assays demonstrated that the flavin-carrying proteins were not recognized by alpha Fp-AB. Apparently the flavin moiety in the native protein conformation was inaccessible to alpha Fp-AB. This conclusion was supported by the absence of an immunoreaction between the riboflavin-binding protein from egg white and alpha FP-AB. Intravenous application of vitamin B2 to rabbits immunized with 6-hydroxy-D-nicotine oxidase, a bacterial protein carrying covalently attached FAD, did not neutralize alpha Fp-AB which had been raised in the serum of the animals. FAD-carrying peptides generated from 6-hydroxy-D-nicotine oxidase by trypsin and chymotrypsin treatment were not recognized by the alpha Fp-AB, but those generated by endopeptidase Lys were. This demonstrates that the epitope recognized by alpha Fp-AB comprises, besides the flavin moiety, protein secondary structure elements.     

用组织多普勒技术评价扩张型心肌病室壁运动

目的　用组织多普勒技术分析扩张型心肌病 (DCM)室壁运动。方法　选择 DCM患者和正常对照各 30例 ,用组织多普勒技术于胸骨旁长轴检测室间隔及左室后壁中间段短轴方向心肌运动速度 (MV) ,并计算心肌运动速度阶差 (MVG) ;经心尖窗检测左室前、后、下、侧壁和前、后室间隔中间段长轴方向 MV。结果　 DCM组患者有 4种 MV频谱异常表现 ,且 MV明显低于对照组 (P<0 .0 5 ) ,并以长轴为甚 ;MVG明显减低 (P<0 .0 5 ) ;室壁各种速度差异消失。结论　组织多普勒技术可定量反映 DCM患者室壁运动异常     

黄芪多糖对糖尿病大鼠心肌超微结构的影响

目的 观察黄芪多糖（APS）对链脲左菌素（STZ）糖尿病大鼠物质代谢、心肌超微结构的影响。方法 SD大鼠腹腔注射STZ以建立糖尿病模型（DM）,成模后分组,APS组每日给予黄芪多糖灌胃,DM组每日给予生理盐水灌胃作为对照。另设一正常对照组。实验6周后采血,测血糖、血脂,电镜观察心肌超微结构,原子吸收光谱测心肌钙含量。结果 APS组的血糖、三酰甘油水平和心肌钙含量较DM组明显降低,电镜下心肌超微结构的异常明显减轻。结论 APS可以改善STZ糖尿病大鼠的物质代谢,对其心肌超微结构也有保护作用。     

扩张性心肌病患者骨代谢指标状况及其临床意义

目的探究扩张性心肌病(dilated cardiomyopathy,DCM)患者骨代谢指标水平状况及其临床意义。方法选取2016年3月至2018年3月在我院诊治的DCM患者48例作为研究对象并归入DCM组,选择同期在我院接受健康体检的成年人30名归入健康组,测定和比较两组的血清骨钙素(BGP)、钙(ICa)、骨特异性碱性磷酸酶(BALP)、甲状旁腺激素(PTH)、25羟基维生素D_3[25(OH) D_3]等骨代谢指标水平,以及大粗隆、股骨颈、腰椎等部位的骨密度(BMD),分析骨代谢指标BGP、ICa、BALP、PTH和25(OH) D_3分别与患者年龄、DCM病程、BMI、肌酸激酶同工酶、肌钙蛋白I和心功能分级等因素的相关性。结果(1) DCM组的BGP、ICa、25(OH) D_3等水平均低于健康组,BALP、PTH水平均高于健康组,差异均有统计学意义(P均0.05)。(2) DCM组大粗隆部位的BMD与健康组比较,差异无统计学意义(P0.05); DCM组的股骨颈及腰椎部位的BMD均低于健康组,差异均有统计学意义(P均0.05)。(3) BGP、ICa和25(OH) D_3分别与年龄、DCM病程及心功能分级呈负相关,BGP与肌酸激酶同工酶、肌钙蛋白Ⅰ呈负相关; BALP与年龄、DCM病程、肌酸激酶同工酶、肌钙蛋白Ⅰ及心功能分级呈正相关,PTH与心功能分级呈正相关(P均0.05)。结论 DCM患者的血清BGP、ICa、BALP、PTH、25(OH) D_3等骨代谢相关指标水平有明显波动,且骨代谢相关指标水平与DCM患者年龄、病程、肌酸激酶同工酶、肌钙蛋白Ⅰ及心功能分级等相关,DCM可能是造成骨代谢指标水平发生异常的重要原因。     

Prevention of hepatitis B mother-to-child transmission in Namibia: A cost-effectiveness analysis

Despite access to a safe and effective vaccine, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) persists in Africa. This is of concern since perinatally-infected infants are at highest risk of developing hepatocellular carcinoma, a life-threatening consequence of chronic HBV infection. While tools to prevent HBV MTCT are available, the cost implications of these interventions need consideration prior to implementation. A Markov model was developed to determine the costs and health outcomes of (1) universal HBV birth dose (BD) vaccination, (2) universal BD vaccination and targeted hepatitis B immunoglobulin (HBIG), (3) maternal antiviral prophylaxis using sequential HBV viral load testing added to HBV BD vaccination and HBIG, and (4) maternal antiviral prophylaxis using sequential HBeAg testing combined with HBV BD vaccination and HBIG. Health outcomes were assessed as the number of paediatric infections averted and disability-adjusted life years (DALYs) averted. Primary cost data included consumables, human resources, and hospital facilities. HBV epidemiology, transitions probabilities, disability weights, and the risks of HBV MTCT were extracted from the literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare successive more expensive interventions to the previous less expensive one. One-way sensitivity analyses were conducted to test the robustness of the model’s outputs. At the Namibian cost/DALY averted threshold of US$3 142, the (1) BD vaccination + targeted HBIG, and (2) maternal antiviral prophylaxis with sequential HBeAg testing interventions were cost-effective. These interventions had ICERs equal to US$1909.03/DALY and US$2598.90/DALY averted, respectively. In terms of effectiveness, the maternal antiviral prophylaxis with sequential HBeAg testing intervention was the intervention of choice. The analysis showed that elimination of HBV MTCT is achievable using maternal antiviral prophylaxis with active and passive immunization. There is an urgent need for low cost diagnostic tests to identify those women who will most benefit from drug therapy to attain this laudable goal.