婴幼儿先天性心脏病术后床边胸片的临床应用评价

评价床边胸片在婴幼儿先天性心脏病术后的临床应用价值,总结其常见并发症以提高阅片正确率。方法:55例先天性心脏病术后婴幼儿患者,男34例,女24例,年龄1月至36月(平均12．8月),其术后均使用移动X线机摄取床边胸片,总结分析术后胸片新出现的异常表现。结果:55例先天性心脏病惠儿术后床边胸片中,发现31例新出现异常X线表现,发生率为56．4%。其中胸腔积液12例;气胸9例,其中4例合并皮下气肿;肺不张5例;左下肺炎3例;肺水肿1例;膈肌抬高1例。婴幼儿先天性心脏病术后最常见的并发症中前三位的依次为:胸腔积液、气胸和肺不张,分别占38．7%、29．0%、16．1%。结论:床边胸片是及时全面了解先天性心脏病患儿术后胸部出现新异常的重要和有效的检查手段,且简便易行,能将婴幼儿不能主诉的影响减至最低,从而为临床提供及时的诊疗依据。     

Transforming growth factor-beta-stimulated endocardial cell transformation is dependent on Par6c regulation of RhoA

Valvular heart disease due to congenital abnormalities or pathology is a major cause of mortality and morbidity. Understanding the cellular processes and molecules that regulate valve formation and remodeling is required to develop effective therapies. In the developing heart, epithelial-mesenchymal transformation (EMT) in a subpopulation of endocardial cells in the atrioventricular cushion (AVC) is an important step in valve formation. Transforming growth factor-beta (TGFbeta) has been shown to be an important regulator of AVC endocardial cell EMT in vitro and mesenchymal cell differentiation in vivo. Recently Par6c (Par6) has been shown to function downstream of TGFbeta to recruit Smurf1, an E3 ubiquitin ligase, which targets RhoA for degradation to control apical-basal polarity and tight junction dissolution. We tested the hypothesis that Par6 functions in a pathway that regulates endocardial cell EMT. Here we show that the Type I TGFbeta receptor ALK5 is required for endocardial cell EMT. Overexpression of dominant negative Par6 inhibits EMT in AVC endocardial cells, whereas overexpression of wild-type Par6 in normally non-transforming ventricular endocardial cells results in EMT. Overexpression of Smurf1 in ventricular endocardial cells induces EMT. Decreasing RhoA activity using dominant negative RhoA or small interfering RNA in ventricular endocardial cells also increases EMT, whereas overexpression of constitutively active RhoA in AVC endothelial cells blocks EMT. Manipulation of Rac1 or Cdc42 activity is without effect. These data demonstrate a functional role for Par6/Smurf1/RhoA in regulating EMT in endocardial cells.     

Genotype Distribution,Viral Load and Clinical Characteristics of Infants with Postnatal or Congenital Cytomegalovirus Infection

Background

Congenital cytomegalovirus infection is a leading cause of long-term sequelae. Cytomegalovirus is also frequently transmitted to preterm infants postnatally, but these infections are mostly asymptomatic. A correlation between cytomegalovirus genotypes and clinical manifestations has been reported previously in infants with congenital infection, but not in preterm infants with postnatal infection.

Objectives

The main objective of this study was to investigate cytomegalovirus genotype distribution in postnatal and congenital cytomegalovirus infection and its association with disease severity.

Methods

Infants admitted to the neonatal intensive care unit of the University Medical Center Utrecht, The Netherlands between 2003–2010 and diagnosed with postnatal or congenital cytomegalovirus infection were included. Classification of cytomegalovirus isolates in genotypes was performed upon amplification and sequencing of the cytomegalovirus UL55 (gB) and UL144 genes. Clinical data, cerebral abnormalities, neurodevelopmental outcome and viral load were studied in relation to genotype distribution.

Results

Genotyping results were obtained from 58 preterm infants with postnatal cytomegalovirus infection and 13 infants with congenital cytomegalovirus infection. Postnatal disease was mild in all preterm infants and all had favourable outcome. Infants with congenital infection were significantly more severely affected than infants with postnatal infection. Seventy-seven percent of these infants were symptomatic at birth, 2/13 died and 3/13 developed long-term sequelae (median follow-up 6 (range 2–8) years). The distribution of cytomegalovirus genotypes was comparable for postnatal and congenital infection. UL55 genotype 1 and UL144 genotype 3 were predominant genotypes in both groups.

Conclusions

Distribution of UL55 and UL144 genotypes was similar in asymptomatic postnatal and severe congenital CMV infection suggesting that other factors rather than cytomegalovirus UL55 and UL144 genotype are responsible for the development of severe disease.     

Multifocal periventricular leukomalacia in children up to 1 year of life

The authors present an analysis of the multifocal leucoencephalomalacia in children under 1 year of life based on the material obtained from 2.398 autopsies. It was found that 32 autopsied children suffered from this disease (1.33%). Twenty four of these children were premature. The disease was more frequent in the infants (23 cases) than in neonates (9 cases), and in boys (20 cases) than in girls (12 cases). Multifocal leucoenephalomalacia was manifested mainly as spastic infantile paralysis in the majority of the infants (14 cases). Morphological lesions to the brain most frequently embraced white substance adjacent to the cerebral ventricles (foci of leucoencephalomalacia of 1 cm in diameter) and cerebral vessels. Widening of the ventricular system of the brain was seen in 15 cases. Pathological reaction resulted from the brain anoxia and ischemia in perinatal period (20 cases) or septicaemia (12 cases) while predisposing factors included: prematurity, respiratory failure with hyaline membranes in the lungs and congenital abnormalities of the heart.     

Atrioventricular cushion transformation is mediated by ALK2 in the developing mouse heart

Developmental abnormalities in endocardial cushions frequently contribute to congenital heart malformations including septal and valvular defects. While compelling evidence has been presented to demonstrate that members of the TGF-beta superfamily are capable of inducing endothelial-to-mesenchymal transdifferentiation in the atrioventricular canal, and thus play a key role in formation of endocardial cushions, the detailed signaling mechanisms of this important developmental process, especially in vivo, are still poorly known. Several type I receptors (ALKs) for members of the TGF-beta superfamily are expressed in the myocardium and endocardium of the developing heart, including the atrioventricular canal. However, analysis of their functional role during mammalian development has been significantly complicated by the fact that deletion of the type I receptors in mouse embryos often leads to early embryonal lethality. Here, we used the Cre/loxP system for endothelial-specific deletion of the type I receptor Alk2 in mouse embryos. The endothelial-specific Alk2 mutant mice display defects in atrioventricular septa and valves, which result from a failure of endocardial cells to appropriately transdifferentiate into the mesenchyme in the AV canal. Endocardial cells deficient in Alk2 demonstrate decreased expression of Msx1 and Snail, and reduced phosphorylation of BMP and TGF-beta Smads. Moreover, we show that endocardial cells lacking Alk2 fail to delaminate from AV canal explants. Collectively, these results indicate that the BMP type I receptor ALK2 in endothelial cells plays a critical non-redundant role in early phases of endocardial cushion formation during cardiac morphogenesis.     

Can folic acid protect against congenital heart defects in down syndrome?

BACKGROUND: Several studies have suggested a protective effect of folic acid (FA) on congenital heart anomalies. Down syndrome (DS) infants are known to have a high frequency of heart anomalies. Not all children with DS suffer from heart anomalies, which raises the question whether maternal factors might affect the risk of these anomalies. Our objectives were to investigate whether first-trimester FA use protects against heart anomalies among DS children. METHODS: Women with liveborn DS children participating in the Slone Epidemiology Center Birth Defects Study between 1976 and 1997 were included. We performed case-control analyses using DS, with heart anomalies as cases and DS, without heart anomalies as controls. Subanalyses were performed for defects that have been associated with FA in non-DS populations (conotruncal, ventricular septal [VSD]) and for those that are associated with DS (ostium secundum type atrial septal defects [ASD] and endocardial cushion defects [ECD]). Exposure was defined as the use of any FA-containing product for an average of at least 4 days per week during the first 12 weeks of pregnancy, whereas no exposure was defined as no use of FA in these 12 weeks. RESULTS: Of the 223 cases, 110 (49%) were exposed versus 84 (46%) of the 184 controls. After adjustment for possible confounders, no protective effect of FA was found on heart anomalies overall (OR 0.95, 95% CI: 0.61-1.47) nor separately for conotruncal defects, VSDs, ASDs, or ECDs. CONCLUSIONS: Our study does not show a protective effect of FA on heart anomalies among infants with DS.     

Infants with single ventricle: a population-based epidemiological study

BACKGROUND: Single ventricle, a rare congenital cardiac defect, often occurs as part of a complex group of cardiovascular abnormalities. Little is known of its epidemiologic associations. METHODS: Using data from the Baltimore-Washington Infant Study [BWIS], (1981-89), a population based case-control study of cardiovascular malformations, infants with single ventricle were evaluated with respect to infant and family characteristics and maternal and paternal exposures. The cases were analyzed according to presence/absence of abnormal cardio-visceral situs. Controls were 3,572 infants without heart defects randomly selected from the regional cohort of live births. Odds ratios and 95% confidence intervals were used as measures of association. RESULTS: Single ventricle occurred in 1.25% of infants with congenital cardiovascular defects in the BWIS. Fifty-five infants had single ventricle. In 48 families (87.3%) the parents were interviewed. Thirty-three infants had normal situs and 15 had abnormal situs. Paternal alcohol consumption (OR = 2.0, 95% CI 1.1-3.9) and paternal cigarette smoking (OR = 2.4, 95% CI 1.1-5.1) were associated with all cases of single ventricle. These associations were even stronger in the subset of infants with abnormal situs. Maternal history of a previous induced abortion was also associated with infants born with abnormal situs (OR = 3.2, 95% CI 1.1-11.5). Paternal marijuana use was associated with cases of single ventricle in normal situs (OR = 2.2, 95% CI 1.0-5.2). CONCLUSIONS: Potential risk factors included paternal smoking and alcohol consumption, highlighting the need for future studies to consider environmental factors in the pathogenesis of this cardiac defect.     

Anti-SSA/Ro antibodies and the heart: more than complete congenital heart block? A review of electrocardiographic and myocardial abnormalities and of treatment options

Apart from complete and incomplete congenital heart block (CHB), new cardiac manifestations related to anti-SSA/Ro antibodies have been reported in children born to mothers bearing these antibodies. These manifestations include transient fetal first-degree heart block, prolongation of corrected QT (QTc) interval, sinus bradycardia, late-onset cardiomyopathy, endocardial fibroelastosis and cardiac malformations. Anti-SSA/Ro antibodies are not considered pathogenic to the adult heart, but a prolongation of the QTc interval has recently been reported in adult patients and is still a matter of debate. Treatment of CHB is not well established and needs to be assessed carefully. The risks and benefits of prenatal fluorinated steroids are discussed.     

Maternal severe migraine and risk of congenital limb deficiencies

BACKGROUND: Migraines occurs frequently during pregnancy; however, there are no published data on their possible teratogenic potential in a controlled epidemiological study. Therefore, we examined the risk of congenital abnormalities in infants born to women who had migraines and other headaches during pregnancy. METHODS: Between 1980 and 1996, the Hungarian Case-Control Surveillance of Congenital Abnormalities evaluated 22,843 cases (newborns or fetuses) with congenital abnormalities, 38,151 control newborn infants without any abnormalities, and 834 malformed controls with Down syndrome. RESULTS: Migraines anytime during pregnancy occurred in 565 (2.5%) mothers of the case group compared with 713 (1.9%) mothers in the control group (crude prevalence odds ratio [POR], 1.3; 95% confidence interval [CI], 1.2-1.5) and 24 (2.9%) pregnant women in the malformed control group (crude POR, 0.9; 95% CI, 0.6-1.3) The mothers of 247 cases, 533 controls, and 21 malformed controls had severe migraines during the second and/or third months of pregnancy. There was only 1 congenital abnormality group: limb deficiencies, which had a higher rate of maternal migraines during the second and third months of pregnancy both at the comparison of cases and matched controls (adjusted POR, 2.5; 95% CI, 1.1-5.8) and of cases and malformed controls (adjusted POR, 1.7; 95% CI, 1.3-3.0). There was no association between other headaches and different congenital abnormalities at the comparison of cases and controls. CONCLUSIONS: Our data showed that maternal severe migraines during the second and/or third months of pregnancy were associated with an increased risk of congenital limb deficiencies. A similar association was not detected between congenital anomalies and other headaches during pregnancy. Our study was not based on a prior hypothesis; therefore, these data can be considered only as a signal that needs confirmation by independent data sets.     

Congenital and Postnatal CMV and EBV Acquisition in HIV-Infected Zimbabwean Infants

Background

HIV-infected infants in sub-Saharan Africa have rapid disease progression. We hypothesized that co-infection with cytomegalovirus (CMV) or Epstein Barr virus (EBV) increases mortality in HIV-infected infants.

Methods

257 antiretroviral therapy-naïve HIV-infected Zimbabwean infants were tested for CMV and EBV at 6 weeks of age by real-time PCR; if positive, birth samples were retrieved where available to distinguish congenital and postnatal infection. The impact of co-infection on mortality through 6 months was estimated using Kaplan-Meier and Cox proportional hazards methods.

Results

At 6 weeks, 203/257 (79%) HIV-infected infants were CMV-positive; 27 (11%) had congenital CMV, 108 (42%) postnatal CMV and 68 (26%) indeterminate timing of infection. By 6 months, 37/108 (34%) infants with postnatal CMV versus 16/54 (30%) CMV-negative infants died (adjusted hazard ratio (aHR) 1.1 [95%CI 0.6, 2.2]). At 6 weeks, 33/257 (13%) HIV-infected infants had EBV co-infection; 6 (2%) had congenital EBV, 18 (7%) postnatal EBV and 9 (4%) indeterminate timing of infection. By 6 months, 5/18 (28%) infants with postnatal EBV versus 72/224 (32%) EBV-negative infants died (aHR 0.8 [95%CI 0.3, 2.3]).

Conclusions

The vast majority of HIV-infants had acquired CMV by 6 weeks, and EBV co-infection occurred earlier than expected, with one in eight HIV-infected infants positive for EBV by 6 weeks. There was a high prevalence of congenital CMV infection and we identified 6 infants with congenital EBV infection, which has not previously been reported in Africa or in the context of HIV infection. Neither CMV nor EBV co-infection was associated with increased mortality.     

Convective tissue movements play a major role in avian endocardial morphogenesis

Endocardial cells play a critical role in cardiac development and function, forming the innermost layer of the early (tubular) heart, separated from the myocardium by extracellular matrix (ECM). However, knowledge is limited regarding the interactions of cardiac progenitors and surrounding ECM during dramatic tissue rearrangements and concomitant cellular repositioning events that underlie endocardial morphogenesis. By analyzing the movements of immunolabeled ECM components (fibronectin, fibrillin-2) and TIE1 positive endocardial progenitors in time-lapse recordings of quail embryonic development, we demonstrate that the transformation of the primary heart field within the anterior lateral plate mesoderm (LPM) into a tubular heart involves the precise co-movement of primordial endocardial cells with the surrounding ECM. Thus, the ECM of the tubular heart contains filaments that were associated with the anterior LPM at earlier developmental stages. Moreover, endocardial cells exhibit surprisingly little directed active motility, that is, sustained directed movements relative to the surrounding ECM microenvironment. These findings point to the importance of large-scale tissue movements that convect cells to the appropriate positions during cardiac organogenesis.     

Extended fetal echocardiographic examination for detecting cardiac malformations in low risk pregnancies.

OBJECTIVE--To improve the rate of prenatal detection of cardiac malformations in a low risk population. DESIGN--Comparison of extended fetal echocardiography with the standard four chamber view in detecting abnormalities. Extended echocardiography comprised the four chamber view and visualisation of the left ventricular outflow tract, the right ventricular outflow tract, and the main pulmonary artery and its branches. In cases with abnormal results complete echocardiographic studies were performed by a paediatric cardiologist using M mode, Doppler, and colour flow mapping techniques. SETTING--Obstetric ultrasonographic unit at Shaare-Zedek Medical Centre, Jerusalem. SUBJECTS--5400 fetuses in low risk pregnancies between 18 and 24 weeks'' gestation (mean 21 weeks); 53 were lost to follow up. MAIN OUTCOME MEASURES--Detection of abnormality before and after birth. RESULTS--During the study 23 infants (0.4%) were born with cardiac abnormalities, 21 of whom had major structural and functional heart disease. 18 fetuses had heart disease diagnosed prenatally, 11 by the four chamber view alone (sensitivity 48%) and a further seven by extended echocardiography (sensitivity 78%). Five fetal cardiac defects were missed prenatally (false negative rate 22%). These included coarctation of aorta, persistent truncus arteriosus, tetralogy of Fallot, ventricular septal defect, and pulmonic stenosis. Only one false positive diagnosis (coarctation of aorta) was made (specificity 99.9%, false positive rate 0.1%). The abnormality was correctly identified in 17 out of 18 cases. CONCLUSIONS--The extended fetal heart examination detected 86% (18/21) of major abnormalities in a low risk population. The examination should be incorporated into routine prenatal ultrasonographic investigations.     

Noninvasive reconstruction of the three-dimensional ventricular activation sequence during pacing and ventricular tachycardia in the canine heart

Single-beat imaging of myocardial activation promises to aid in both cardiovascular research and clinical medicine. In the present study we validate a three-dimensional (3D) cardiac electrical imaging (3DCEI) technique with the aid of simultaneous 3D intracardiac mapping to assess its capability to localize endocardial and epicardial initiation sites and image global activation sequences during pacing and ventricular tachycardia (VT) in the canine heart. Body surface potentials were measured simultaneously with bipolar electrical recordings in a closed-chest condition in healthy canines. Computed tomography images were obtained after the mapping study to construct realistic geometry models. Data analysis was performed on paced rhythms and VTs induced by norepinephrine (NE). The noninvasively reconstructed activation sequence was in good agreement with the simultaneous measurements from 3D cardiac mapping with a correlation coefficient of 0.74 ± 0.06, a relative error of 0.29 ± 0.05, and a root mean square error of 9 ± 3 ms averaged over 460 paced beats and 96 ectopic beats including premature ventricular complexes, couplets, and nonsustained monomorphic VTs and polymorphic VTs. Endocardial and epicardial origins of paced beats were successfully predicted in 72% and 86% of cases, respectively, during left ventricular pacing. The NE-induced ectopic beats initiated in the subendocardium by a focal mechanism. Sites of initial activation were estimated to be ～7 mm from the measured initiation sites for both the paced beats and ectopic beats. For the polymorphic VTs, beat-to-beat dynamic shifts of initiation site and activation pattern were characterized by the reconstruction. The present results suggest that 3DCEI can noninvasively image the 3D activation sequence and localize the origin of activation of paced beats and NE-induced VTs in the canine heart with good accuracy. This 3DCEI technique offers the potential to aid interventional therapeutic procedures for treating ventricular arrhythmias arising from epicardial or endocardial sites and to noninvasively assess the mechanisms of these arrhythmias.     

Endocardial Endothelial Dysfunction Progressively Disrupts Initially Anti then Pro-Thrombotic Pathways in Heart Failure Mice

Objective

An experimental model of endocardial thrombosis has not been developed and endocardial endothelial dysfunction in heart failure (HF) is understudied. We sought to determine whether disruption of the endothelial anti-coagulant activated protein C (APC) pathway in CREB_A133 HF mice promotes endocardial thrombosis in the acute decompensated phase of the disease, and whether alterations in von Willebrand factor (vWF) secretion from HF endocardium reduces thrombus formation as HF stabilizes.

Approach and results

Echocardiography was used to follow HF development and to detect endocardial thrombi in CREB_A133 mice. Endocardial thrombi incidence was confirmed with immunohistochemistry and histology. In early and acute decompensated phases of HF, CREB_A133 mice had the highest incidence of endocardial thrombi and these mice also had a shorter tail-bleeding index consistent with a pro-thrombotic milieu. Both APC generation, and expression of receptors that promote APC function (thrombomodulin, endothelial protein C receptor, protein S), were suppressed in the endocardium of acute decompensated HF mice. However, in stable compensated HF mice, an attenuation occurred for vWF protein content and secretion from endocardial endothelial cells, vWF-dependent platelet agglutination (by ristocetin), and thrombin generation on the endocardial surface.

Conclusions

CREB_A133 mice develop HF and endocardial endothelial dysfunction. Attenuation of the anti-coagulant APC pathway promotes endocardial thrombosis in early and acute decompensated phases of HF. However, in stable compensated HF mice, disruptions in endothelial vWF expression and extrusion may actually reduce the incidence of endocardial thrombosis.     

小儿心内膜纤维弹力组织增生症临床病理观察

目的:进一步认识小儿心内膜纤维弹力组织增生症的临床病理学特征。方法:收集我院3例尸检及1例心内膜心肌活检病例,结合临床病史、心电图、心脏超声心动检查及病理学常规及特殊染色。结果:心脏形态学改变,表现为心脏增大,质量增加,以左心室增大为主,右心室也可增大;心内膜呈弥漫或不规则增厚。光镜下,心内膜弹力纤维及胶原纤维明显增生,平行排列呈十余层,弹力纤维染色阳性。结论:本病预后差,病理诊断应与心内膜心肌纤维化病进行鉴别,必要时做心内膜活检确诊。     

Comparison of echocardiography and 64-slice spiral computed tomography in the diagnosis of congenital heart disease in children

The diagnosis of congenital heart disease in children has been an issue in the medical community. Timely diagnosis and treatment can provide a greater guarantee for children's healthy growth. In recent years, there have been more and more studies on the diagnosis of congenital heart disease in children. This paper compares the advantages and disadvantages of echocardiography and 64-slice spiral computed tomography (CT) in the diagnosis of congenital heart disease in children. In clinical trials, we also tested 64 patients with spiral computed tomography (SCT) and transthoracic echocardiography (TTE) detection of patients and then confirmed the accuracy of the diagnosis by the surgical methods. The two methods of detection, the rate of missed diagnosis, and the rate of misdiagnosis were counted. Through the test results and pathological diagnosis results, the diagnostic accuracy of the two methods were all above 90%, each with its own advantages and disadvantages. The sensitivity of echocardiographic in detecting intracardiac structure abnormalities was relatively high, but when the diagnosis of extracardiac structural abnormalities less than 64-slice spiral CT method, misdiagnosis of TTE was mainly due to extracardiac vascular malformations. Therefore, it is recommended to combine the two methods to improve the diagnosis of congenital heart disease in children.     

Lectin histochemistry of the embryonic heart: expression of terminal and penultimate galactose residues in developing rats and chicks

Rat embryos at days 10-18 of gestation and chicken embryos at days 3-6 of incubation were fixed and processed for lectin histochemistry. The distribution of binding sites for a lectin from the peanut Arachis hypogaea (PNA) conjugated to horseradish peroxidase (HRP) was determined on tissue sections both before and after enzymatic cleavage of sialic acid with neuraminidase (sialidase). Endocardial cushion tissue in the rat, but not in the chick, reacted with PNA-HRP prior to digestion with sialidase. Endocardium of both species (12 and 13 days in rat, 5 and 6 days in chick), particularly at the level of endocardial cushions, reacted strongly with the sialidase-PNA sequence; this staining decreased markedly after day 14 of gestation in the rat. PNA binding sites capped by sialic acid were most abundant in the developing rat heart during the critical period of endocardial cushion formation and decreased as development proceeded. The marked changes in the appearance and distribution of cardiac cell and tissue glycoconjugates during cardiogenesis support the concept that rapid changes occur in the structure of complex carbohydrates during embryonic and fetal development. The findings also suggest that such glycosylation-related events may be species specific.     

What chick and mouse models have taught us about the role of the endocardium in congenital heart disease

Specific cell and tissue interactions drive the formation and function of the vertebrate cardiovascular system. Although much attention has been focused on the muscular components of the developing heart, the endocardium plays a key role in the formation of a functioning heart. Endocardial cells exhibit heterogeneity that allows them to participate in events such as the formation of the valves, septation of the outflow tract, and trabeculation. Here we review, the contributions of the endocardium to cardiovascular development and outline useful approaches developed in the chick and mouse that have revealed endocardial cell heterogeneity, the signaling molecules that direct endocardial cell behavior, and how these insights have contributed to our understanding of cardiovascular development and disease.