Diagnosis and treatment of incomplete Kawasaki disease in children / 中国当代儿科杂志

Kawasaki disease (KD) is a febrile disease mainly observed in children aged <5 years, with medium- and small-vessel vasculitis as the main lesion. Although KD has been reported for more than 50 years and great progress has been made in the etiology and pathology of KD in recent years, there is still a lack of specific indicators for the early diagnosis of KD, especially with more difficulties in the diagnosis of incomplete Kawasaki disease (IKD). At present, there are no clear diagnostic criteria for IKD, which leads to the failure of the timely identification and standardized treatment of IKD in clinical practice and even induce the development of coronary artery lesion. This article reviews the concept, epidemiological features, diagnosis, treatment, and follow-up management of IKD, in order to deepen the understanding of IKD among clinical workers and help to improve the clinical diagnosis and treatment of KD in China.

Association of liver damage with coronary artery lesion and no response to intravenous immunoglobulin in the acute stage of Kawasaki disease / 中国当代儿科杂志

OBJECTIVES@#To summarize the clinical features of liver damage in children in the acute stage of Kawasaki disease (KD), and to investigate the clinical value of liver damage in predicting coronary artery lesion and no response to intravenous immunoglobulin (IVIG) in children with KD.@*METHODS@#The medical data were collected from 925 children who were diagnosed with KD for the first time in Beijing Children's Hospital from January 1, 2016 to December 31, 2017. According to the presence or absence of abnormal alanine aminotransferase (ALT) level on admission, the children were divided into a liver damage group (n=284) and a non-liver damage group (n=641). A logistic regression analysis was used to investigate the clinical value of the indicators including liver damage in predicting coronary artery lesion and no response to IVIG in children with KD.@*RESULTS@#Compared with the non-liver damage group, the liver damage group had a significantly earlier admission time and significantly higher serum levels of inflammatory indicators (P<0.05). The liver damage group had a significantly higher incidence rate of coronary artery lesion on admission than the non-liver damage group (P=0.034). After initial IVIG therapy, the liver damage group had a significantly higher proportion of children with no response to IVIG than the non-liver damage group (P<0.001). In children with KD, coronary artery lesion was associated with the reduction in the hemoglobin level and the increases in platelet count, C-reactive protein, and ALT (P<0.05), and no response to IVIG was associated with limb changes, the reduction in the hemoglobin level, the increases in platelet count, C-reactive protein, and ALT, and coronary artery lesion (P<0.05).@*CONCLUSIONS@#Compared with those without liver damage, the children in the early stage of KD with liver damage tend to develop clinical symptoms early and have higher levels of inflammatory indicators, and they are more likely to have coronary artery lesion and show no response to IVIG treatment.

Detection of Subclinical Anthracyclines' Cardiotoxicity in Children with Solid Tumor / 中华医学杂志(英文版)

<p><b>Background</b>Cardiotoxicity is one of the most serious chronic complications of anthracyclines therapy. Assessment of the left ventricular ejection fraction (LVEF) fails to detect subtle cardiac dysfunction of left ventricular (LV). This study aimed to detect and evaluate new parameters of subclinical anthracyclines' cardiotoxicity in children with solid tumor.</p><p><b>Methods</b>A detailed echocardiographic examination was performed in 36 children with hepatoblastoma or rhabdomyosarcoma after receiving anthracyclines' chemotherapy and 36 healthy controls from January 2015 to December 2016. The LVEF, ratio of early diastolic peak velocity of transmitral flow (E) and septal diastolic e' mitral annular peak velocity (e'), tricuspid annular plane systolic excursion (TAPSE), and LV global longitudinal strain (GLS) were evaluated using M-mode, tissue Doppler imaging (TDI), and two-dimensional speckle tracking echocardiography (2D-STE), respectively. Echocardiographic parameters were compared between patient group and healthy controls. All patients were divided into two subgroups based on their anthracyclines' cumulative dosage (<300 mg/m subgroup and ≥300 mg/m subgroup).</p><p><b>Results</b>All patients had no presentation of heart failure and LVEF within normal range (65.7 ± 5.1%). Compared with healthy controls, the mean E/e' increased significantly (7.9 ± 0.7 vs. 10.2 ± 3.5, t = 3.72, P < 0.01), mean TAPSE decreased significantly (17.2 ± 1.3 mm vs. 14.2 ± 3.0 mm, t = -4.03, P < 0.01), and mean LV GLS decreased significantly (-22.2% ± 1.9% vs. -17.9% ± 2.9%, t = -5.58, P < 0.01) in patient group. Compared with subgroup with anthracyclines' cumulative dosage < 300 mg/m, mean LV GLS decreased significantly (-18.7 ± 2.7% vs. -16.5 ± 2.1%, t = 2.15, P = 0.04), the mean E/e' increased significantly (9.1 ± 1.5 vs. 11.5 ± 4.9, t = -2.17, P = 0.04), and mean TAPSE decreased significantly (14.2 ± 2.1 mm vs. 12.5 ± 2.2 mm, t = -2.82, P = 0.02) in subgroup with anthracyclines' cumulative dosage ≥300 mg/m.</p><p><b>Conclusions</b>LV GLS is helpful in the early detection of subclinical LV dysfunction using 2D-STE. E/e' and TAPSE are other sensitive parameters in detecting subclinical cardiac dysfunction of both ventricles by TDI. These parameters show significant change with different anthracyclines' cumulative dosage, so cumulative dosage should be controlled in clinical treatment.</p>

Echocardiographic Evaluation of Coronary Abnormalities and Cardiac Function in a Murine Model of Kawasaki Disease Using High-frequency Ultrasound / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Murine model of coronary arterial inflammation has been widely accepted as an animal model of and used in Kawasaki disease (KD). This study sought to evaluate the developmental changes of coronary arteries and cardiac function in a murine model of KD with a high-frequency ultrasound system and to provide evidence for the preparation of the model of KD.</p><p><b>METHODS</b>Lactobacillus casei cell wall extract was prepared and injected into C57BL/6 mice intraperitoneally (i.p.) to induce KD. A total of 120 mice were grouped into three groups. The intravenous immunoglobulin (IVIG) treatment group was i.p. injected with IVIG (2 g/kg), while the KD model and normal control groups were i.p. injected with 0.5 ml of phosphate buffered solution on day 5. All high-resolution echocardiography detection of mouse heart was performed by the same senior technician. Animal echocardiography was performed by measuring the coronary artery dimensions and cardiac function on days 0, 7, 14, 28, and 56 (high-resolution small animal ultrasound [Vevo770 pattern; VisualSonic, Canada] with broadband probe [RMVTM707B; frequency, 30 mHz; depth of focus, 1.2 cm]) which were measured and analyzed with Vevo770 software.</p><p><b>RESULTS</b>Pathological studies revealed focal inflammatory infiltrate asymmetrically distributed around the coronary artery trunk in the KD model group. Echocardiographic study including coronary dimension and cardiac function measurements was successfully performed in all subjects. The KD model and IVIG treatment groups showed left coronary artery dilation on days 7, 14, 28, and 56. The diameter of left coronary artery in the KD model group (0.53 ± 0.09 mm; 0.36 ± 0.07 mm; 0.34 ± 0.05 mm; 0.34 ± 0.04 mm) was significantly larger than those of IVIG treatment group (0.22 ± 0.02 mm; 0.28 ± 0.03 mm; 0.26 ± 0.03 mm; 0.27 ± 0.05 mm; 0.26 ± 0.03 mm; all P < 0.01) and the normal control group (0.21 ± 0.02 mm; 0.22 ± 0.03 mm; 0.22 ± 0.02 mm; 0.23 ± 0.02 mm; 0.27 ± 0.04 mm; all P< 0.01) on days 7, 14, 28, and 56. No significant differences were observed in the measurements of cardiac function among the groups on days 0, 7, 14, 28, and 56 (all P > 0.05).</p><p><b>CONCLUSIONS</b>Echocardiography could identify the consecutive changes of coronary artery in KD mice. Echocardiography is more convenient and direct in evaluating the coronary abnormalities in this animal model.</p>

Corticosteroid Therapy Might be Associated with the Development of Coronary Aneurysm in Children with Kawasaki Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Coronary artery lesions (CALs) are known to be the main complication in children with Kawasaki disease (KD). Instead of intravenous immunoglobulin (IVIG), corticosteroid therapy has been accepted to be used for children with KD who are unresponsive to IVIG. This study aimed to evaluate risk factors for CALs in children with KD.</p><p><b>METHODS</b>We retrospectively reviewed the clinical records of 2331 children with KD from January 2005 to December 2014. To identify the independent risk factors for CALs, multivariable logistic regression models were constructed using significant variables identified from univariate logistic regression analysis.</p><p><b>RESULTS</b>The incidence of CALs was 36.0% (840 of 2331), including 625 (26.8%) coronary artery dilations and 215 (9.2%) coronary artery aneurysms (CAAs). Multivariable logistic regression analysis identified that male, incomplete KD, longer fever duration, and C-reactive protein (CRP) >100 mg/L were independent risk factors for coronary artery dilatations. On the other hand, male, incomplete KD, longer fever duration, prolonged days of illness at the initial treatment, corticosteroid therapy, sodium ≤133 mmol/L, and albumin <35 g/L were the independent risk factors for CAAs. In addition, corticosteroid therapy, prolonged days of illness at the initial treatment, and albumin <35 g/L were the independent risk factors for giant CAAs.</p><p><b>CONCLUSIONS</b>CALs might be associated with male sex, incomplete KD, longer fever duration, prolonged days of illness at the initial treatment, albumin <35 g/L, sodium ≤133 mmol/L, CRP >100 mg/L, and corticosteroid therapy. Corticosteroid therapy was an independent risk factor for CAAs and giant CAAs. Thus, corticosteroids should be used with caution in the treatment of KD with the risk for CALs.</p>

Salvianolic Acid B Down-regulates Matrix Metalloproteinase-9 Activity and Expression in Tumor Necrosis Factor-α-induced Human Coronary Artery Endothelial Cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Salvianolic acid B (Sal B) is a bioactive water-soluble compound of Salviae miltiorrhizae, a traditional herbal medicine that has been used clinically for the treatment of cardiovascular diseases. This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 (MMP-9) and on the underlying mechanisms in tumor necrosis factor-α± (TNF-α±)-activated human coronary artery endothelial cells (HCAECs), a cell model of Kawasaki disease.</p><p><b>METHODS</b>HCAECs were pretreated with 1-10 αμmol/L of Sal B, and then stimulated by TNF-α± at different time points. The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay, respectively. Nuclear factor-κB (NF-κB) activation was detected with immunofluorescence, electrophoretic mobility shift assay, and Western blot assay. Protein expression levels of mitogen-activated protein kinase (c-Jun N-terminal kinase [JNK], extra-cellular signal-regulated kinase [ERK], and p38) were determined by Western blot assay.</p><p><b>RESULTS</b>After HCAECs were exposed to TNF-α±, 1-10 αμmol/L Sal B significantly inhibited TNF-α±-induced MMP-9 expression and activity. Furthermore, Sal B significantly decreased IκBα± phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α± for 30 min. In addition, Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α± for 10 min.</p><p><b>CONCLUSIONS</b>The data suggested that Sal B suppressed TNF-α±-induced MMP-9 expression and activity by blocking the activation of NF-κB, JNK, and ERK1/2 signaling pathways.</p>

Evaluation of coronary artery diameter in normal children by echocardiography and its clinical significance / 中华儿科杂志

<p><b>OBJECTIVE</b>To obtain normal range of coronary artery diameter with body surface area (BSA) dynamic changes in normal children at different age.</p><p><b>METHOD</b>The left main coronary artery (LCA), left anterior descending artery (LAD), left circumflex artery (LCX) and the right coronary artery (RCA) diameter were measured in 400 normal subjects from Chinese population aged 0 d to 18 years [(6.43 ± 4.45) years], using HP Sonos 5500 color Doppler ultrasonic system, according to the standard method of measuring the coronary artery diameter.</p><p><b>RESULT</b>(1) The diameters of LCA, LAD, LCX and RCA in different age groups (0 d-12 months, -3 years, -6 years, -9 years, -12 years, -18 years) had significant differences (F = 61.688, 51.343, 46.375, 50.192, P < 0.01,all groups mean differences had significant differences, there was significant difference between every two groups, P < 0.05), there were no significant differences between male and female subjects (P > 0.05). (2) The correlation analyses showed that the diameter of LCA, LAD, LCX and RCA had significant linear correlations with age, height, weight and BSA (r ranged from 0.71 to 0.85, P < 0.01 ). (3) The regression analyses were respectively performed on the diameters of LCA, LAD, LCX and RCA with BSA to establish seven regression models. The coefficients were compared for each model, the best model was chosen to create a Z score calculator, tracing out the Z value curve, through clinical practice,we chose Z score within ± 2 as the coronary artery diameter's normal range for Chinese children.</p><p><b>CONCLUSION</b>Coronary artery diameter's Z score curve is effective and reliable, it provide objective basis for clinicians and sonographers to accurately and quickly diagnose the anomalies in diameter of coronary artery.</p>

Warfarin and aspirin combination therapy for giant coronary artery aneurysm secondary to Kawasaki disease / 中华实用儿科临床杂志

Objective To explore whether the warfarin and aspirin combination therapy can prevent cardiovascular events in patients with giant coronary artery aneurysm (GCAA) caused by Kawasaki disease (KD).Methods Children who had been diagnosed as GCAA secondary to KD in Beijing Children's Hospital Affiliated to Capital Medical University between Jan.1998 and Aug.2012 were enrolled in this study.They were divided into the warfarin plus aspirin group (combination group) and aspirin group.The combination group used the therapy of warfarin and small dose aspirin in the long-term anticoagulation treatment,while the aspirin group used small dosage of aspirin without warfarin.Both groups were followed at the time points of 2nd week,1st month,3rd month,6th month,and 1st year after discharge of the acute stage.Then these children were followed every 6 months.Data on each followed-up included clinical manifestations,coronary artery aneurysm recovery situation and complications.Results (1) The onset age of GCAA caused by KD ranged from 3 months to 13 years and 3 months.Infants who were ≤ 1 year old and children who were ≥5 years old were more susceptible to this disease,their proportion were both 23.1％ . (2) The distribution of GCAA in both groups were similar.GCAA most commonly occurred in the right coronary artery,then the left anterior descending coronary artery,and then the main trunk of left coronary artery,the left circumflex artery was rarely affected.(3) Coronary artery aneurysm in 17 cases(53.1％) retracted in the warfarin combined with aspirin group,while 5 cases(41.7％) in the aspirin group.Fifteen cases(46.9％) in the combination group hadn't obvious change,while the aspirin group got 7 cases (58.3 ％).(4) During the follow-up,2 children (6.3 ％) complicated with intracoronary thromboses in the combination group,while 3 cases(25.0％) in the aspirin group.One case(3.1％) in the combination group suffered myocardial infarction,while 3 cases (25.0％) in the asprin group.Two cases (16.7 ％) in the aspirin group died,while none in the combination group.Coronary artery stenosis occurred in 2 cases (16.7％) in the aspirin group,while 1 case (3.1％) in the combination group.One child had coronary artery occlusion in the aspirin group,while none in the combination group.(5)The combination group had 1 case of serious bleeding event,subarachnoid hemorrhage.In addition,there were 8 cases of nasal bleeding,a total of 19 person-time.There was no serious bleeding event in the aspirin group,only 3 person-time small mount of nasal bleeding.Conclusions Althought warfarin plus aspirin therapy for the long-term anticoagulation treatment in GCAA caused by KD can not affect the retraction of GCAA,it may decrease the incidence of thrombosis,myocardial infarction and mortality.Bleeding complication is more common during the application of wafarin.Therefore the dose of warfarin should be tailored in various children according to the clinical situation,and bleeding complication should be monitored.

Effect of granulocyte colony-stimulating factor on endothelial progenitor cell for coronary artery lesion in Kawasaki disease mice model / 中华儿科杂志

<p><b>OBJECTIVE</b>Number and function of endothelial progenitor cell (EPC) and coronary artery lesion in Kawasaki disease (KD) model were evaluated to investigate therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF).</p><p><b>METHOD</b>C57BL/6 mice were injected with L. casei cell wall extract (LCWE); 48 mice were divided into 3 groups randomly: KD model group; G-CSF treated model group and control group, 16 in each. G-CSF was subcutaneously injected from day 5 to day 9 after injection of LCWE. Coronary artery lesion, number of circulating EPC and the function of bone marrow EPC were evaluated.</p><p><b>RESULT</b>In model group, inflammatory infiltration was found around coronary artery at 14 days. The number of circulating EPC was significantly decreased in model group (0.017% ± 0.008%) compared to control (0.028% ± 0.007%) (t = 2.037, P < 0.05). Disruption of elastin was consistently observed at 56 days. Stimulated by G-CSF, inflammatory infiltration was found around the coronary artery at day 14, while the number of circulating EPC (0.042% ± 0.015%) was increased significantly compared to models (t = 4.629, P < 0.05). At the day 56, the number of circulating EPC was decreased slightly (0.029% ± 0.012%), but still higher than the model group (t = 2.789, P < 0.05), and have no significant difference compared to controls (P > 0.05). Furthermore, there was no elastin disruption in the G-CSF group. In model group, bone marrow EPC's proliferation ability of absorbance (A value) was 0.38 ± 0.09 in thiazolyl blue assay, less than controls (0.61 ± 0.14, P < 0.01). Adhesion and migration function were down-regulated compared to controls [(3.1 ± 0.6) cells/HPF and (3.3 ± 0.6) cells/HPF vs. (6.4 ± 1.2) cells/HPF and (6.2 ± 0.5) cells/HPF, both P < 0.01]. In the G-CSF treated group, proliferation ability (A 0.58 ± 0.10), adhesion [(6.17 ± 1.13) cells/HPF], migration [(6.29 ± 0.42) cells/HPF] function were increased significantly compared to the model group (P < 0.01).</p><p><b>CONCLUSION</b>G-CSF can up-regulate EPC number and function to prevent coronary artery lesion in mice model of KD.</p>

Endothelial progenitor cell transplantation ameliorates elastin breakdown in a Kawasaki disease mouse model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Coronary artery damage from Kawasaki disease (KD) is closely linked to the dysfunction of endothelial progenitor cells (EPCs). The aim of the present study was to evaluate the therapeutic effect of EPCs transplantation in KD model.</p><p><b>METHODS</b>Lactobacillus casei cell wall extract (LCWE)-induced KD model in C57BL/6 mice was established. The model mice were injected intravenously with bone marrow-derived in vitro expanded EPCs. Histological evaluation, number of circulating EPCs and the function of bone marrow EPCs were examined at day 56.</p><p><b>RESULTS</b>Inflammation was found around the coronary artery of the model mice after 14 days, Elastin breakdown was observed after 56 days. CM-Dil labeled EPCs incorporated into vessel repairing foci was found. At day 56, the number of peripheral EPCs in the KD model group was lower than in EPCs transplanted and control group. The functional index of bone marrow EPCs from the KD model group decreased in proliferation, adhesion and migration. Increased number of circulating EPCs and improved function were observed on the EPCs transplanted group compared with model group.</p><p><b>CONCLUSION</b>Exogenously administered EPCs, which represent a novel strategy could prevent the dysfunction of EPCs, accelerate the repair of coronary artery endothelium lesion and decrease the occurrence of aneurysm.</p>

Endothelial progenitor cell down-regulation in a mouse model of Kawasaki disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cardiovascular complications of Kawasaki disease (KD) are a common cause of heart disease in pediatric populations. Previous studies have suggested a role for endothelial progenitor cells (EPCs) in coronary artery lesions associated with KD. However, long-term observations of EPCs during the natural progression of this disorder are lacking. Using an experimental model of KD, we aimed to determine whether the coronary artery lesions are associated with down-regulation of EPCs.</p><p><b>METHODS</b>To induce KD, C57BL/6 mice were administered an intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE; phosphate buffered saline used as control vehicle). Study groups included: group A (14 days following LCWE injection), group B (56 days following LCWE injection) and group C (controls). Numbers of circulating EPCs (positively staining for both CD34 and Flk-1 while staining negative for CD45) were evaluated using flow cytometry. Bone marrow mononuclear cells were cultured in vitro to expand EPCs for functional analysis. In vitro EPC proliferation, adhesion and migration were assessed.</p><p><b>RESULTS</b>The model was shown to exhibit similar coronary artery lesions to KD patients with coronary aneurysms. Numbers of circulating EPCs decreased significantly in the KD models (groups A and B) compared to controls ((0.017 ± 0.008)% vs. (0.028 ± 0.007)%, P < 0.05 and (0.016 ± 0.007)% vs. (0.028 ± 0.007)%, P < 0.05). Proliferative, adhesive and migratory properties of EPCs were markedly impaired in groups A and B.</p><p><b>CONCLUSION</b>Coronary artery lesions in KD occur as a consequence of impaired vascular injury repair, resulting from excess consumption of EPCs together with a functional impairment of bone marrow EPCs and their precursors.</p>

Late endothelial function in children with coronary aneurysm due to Kawasaki disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the late endothelial function in children with coronary aneurysm due to Kawasaki disease (KD).</p><p><b>METHODS</b>Thirty-one children with coronary aneurysms due to KD who had the disease course for more than 1 year and twenty-one age-matched healthy children were enrolled. Brachial artery endothelium-dependent and -independent flow-mediated dilation (FMD), carotid arterial stiffness index (SI) and intima-media thickness (IMT) were measured by high-frequency ultrasound.</p><p><b>RESULTS</b>There were 9 cases of medium and 22 cases of giant coronary aneurysms in the KD group. Twelve KD patients had evidence of myocardial ischemia. Compared to the normal controls, the endothelium-dependent FMD decreased (P<0.05), the carotid arterial SI increased (P<0.05), and the carotid arterial intima-media thickness increased significantly (P<0.05) in children with coronary aneurysms due to KD. The endothelium-dependent FMD decreased more significantly in 12 KD patients with myocardial ischemia than in those without any evidence of myocardial ischemia (P<0.05).</p><p><b>CONCLUSIONS</b>Late endothelial dysfunction exists in children with coronary aneurysms due to KD, especially in those with myocardial ischemia.</p>

Congenital vascular rings: a rare cause of respiratory distress in infants and children / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Congenital vascular rings may often cause unexplained respiratory symptoms in infants and young children. Their diagnosis and treatment are often delayed. Few studies of vascular rings have been reported in China. The aim of this study was to describe the clinical presentation, diagnosis and surgical management of infants and children with congenital vascular rings.</p><p><b>METHODS</b>Clinical histories, physical examinations, investigations, image studies and surgical interventions were retrospectively evaluated in 7 children (age range: 2 months-4 years, mean 7 months) with congenital vascular rings. Chest radiography was performed in all patients. Echocardiography and computed tomography (CT) with 3-dimensional (3D) reconstructions were performed in 6 patients. Esophagography, cardiac catheterization and angiography, and bronchoscopy were performed in 1, 1 and 4 children, respectively.</p><p><b>RESULTS</b>Six of the 7 patients had respiratory symptoms, including recurrent cough, stridor and wheeze. Age at onset of symptoms ranged from 1 month to 11 months. Chest X-ray showed nothing important on the vascular rings, besides bronchitis and pneumonia. Contrast-enhanced CT diagnosed vascular rings in 6 patients. Four patients had double aortic arches, two had balanced arches and two were right arch dominant. One patient had a right aortic arch with left ligament and 1 patient had a pulmonary artery sling. Echocardiography failed to diagnose vascular rings in 2 patients. The esophagogram of 1 patient showed esophageal compression. Bronchoscopy of 4 patients showed compression of the distal trachea. Five of the 7 patients underwent surgical division of the vascular rings. Surgical observation confirmed the CT findings in each patient.</p><p><b>CONCLUSIONS</b>Patients, especially infants or young children, with recurrent respiratory symptoms such as chronic cough, stridor and wheeze, should be examined for the possible presence of congenital vascular rings. Contrast-enhanced CT can clearly show the anatomy of vascular rings. As a noninvasive technique, echocardiography is helpful for diagnosis. Early surgical management in symptomatic patients is effective.</p>

A multicenter study on treatment of autonomous nerve-mediated syncope in children with beta-receptor blocker / 中华儿科杂志

<p><b>OBJECTIVE</b>Syncope is a common pediatric emergency. Based on an epidemiologic survey in the USA, around 15% of children experienced syncopal attack, which strongly influenced the life, study and hurt the children mentally and physiologically. Therefore, exploring the therapeutic regimen has become a hot topic in the field of pediatric cardiology. The aim of this study was to examine the effect of beta receptor blocker in the treatment of children with autonomous nerve mediated syncope.</p><p><b>METHODS</b>Totally 103 children (43 males, 60 females, age 5 - 19 yrs, median 12.0 +/- 2.6 yrs) with autonomous nerve mediated syncope from Beijing, Hunan, Hubei and Shanghai, were included in this study. Forty-nine of them suffered from vasovagal syncope (VVS) and 54 suffered from postural tachycardia syndrome (POTS). They were randomly divided into treatment group accepting oral metoprolol treatment and control group accepting oral rehydration salt treatment. The frequency of syncopal episodes and the outcome of head-up tilt (HUT) test were observed. SPSS 10.0 software was used for the statistical analysis of these data.</p><p><b>RESULTS</b>The cure rate of children who suffered from VVS and POTS and took oral metoprolol was 60.61% and 68.75%, respectively, but in the control group, the cure rate was only 18.75% and 0.00%, respectively. The rate of improvement of children who suffered from VVS and POTS and were treated with oral metoprolol was 15.15% and 15.63%, respectively, and in the control group, it was 6.25% and 40.91%, respectively. The effective rates for cases of VVS and POTS treated with oral metoprolol were higher than those of cases received oral rehydration salt treatment (P < 0.01). The percentage of the change from positive HUT to negative for children with VVS and POTS who took oral metoprolol therapy was 60.61% and 68.75%, respectively, but in control group, it was only 18.75% and 9.09%, respectively (P < 0.01). There was a significant difference in the percentage of the change from positive HUT to negative between children with VVS treated with oral metoprolol and with oral rehydration salt (P < 0.01). Also, a significant difference was found in the percentage of the change from positive HUT to negative between children with POTS treated with oral metoprolol and with oral rehydration salt (P < 0.01).</p><p><b>CONCLUSION</b>beta receptor blocker is effective in the treatment of children with VVS or POTS.</p>

Mean values of brain natriuretic peptide in 190 healthy children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Overseas research has shown the value of brain natriuretic peptide (BNP) in the diagnosis and treatment of heart failure in children. However, a reference range of BNP values is lacking, limiting its clinical application. This study was designed to determine a reference range for children aged 1 to 16 years.</p><p><b>METHODS</b>Plasma BNP (BNP32, NT-proBNP) concentrations were measured in 190 healthy children (95 boys and 95 girls) using an enzyme immunoassay. Their age ranged from 1 to 16 years (mean=10.6 +/- 4.2 years).</p><p><b>RESULTS</b>The mean plasma concentration of BNP32 in 190 children was 51.89 +/- 48.36 pg/mL, with the 10th and the 90th percentile rank of 27.00 pg/mL and 75.00 pg/mL respectively. The mean plasma concentration of BNP32 in girls was 60.33 +/- 62.91 pg/mL, and 44.22 +/- 27.14 pg/mL in boys, but no statistical differences were found. The mean plasma concentration of NT-proBNP in 190 children was 246.04 +/- 67.27 fmol/mL. The girls had slightly higher plasma NT-proBNP levels than the boys, but there were no statistical differences between them. Neither plasma BNP32 concentration nor NT-proBNP concentration was related to age.</p><p><b>CONCLUSIONS</b>This study first reported a reference range of BNP values for healthy Chinese children aged 1-16 years. Both age and gender are not related to BNP values.</p>

Etiological Analysis and Differential Diagnosis of Syncope in Children / 实用儿科临床杂志

Objective To study the feature of the etiology of pediatric syncope by cases study,and to discuss the feasibility on identification between the cardiac and neurally-mediated syncope with its inducements and symptoms.Methods One hundred and eleven patients were etiologically classified by standard diagnostic procedure to summarize the inducements,presymptoms and symptoms.The data about cardiac and neurally-mediated syncope were statistically treated to find their characteristic manifestation.Results Among these,60.4% was non-cardiovascular syncope,18.9% was postural hypotension,18.0% was vasovagal syncope and 9% was cardiac syncope.Most of them were non-cardiac syncope and neurally-mediated syncope was on the top,while cardiac syncope was rare in children.Prolonged standing and nausea was the feature of the neurally-mediated syncope,and the cardiac syncope is associated with physical exercise.Conclusions Most pediatric inpatients were non-cardiovascular syncope in which neurally-mediated syncope is first on the list.The movement-related syncope is the feature of the cardiac syncope.The prolonged standing and nausea are due to neurally-mediated syncope.

Changes of N-Terminal Pro-Brain Natriuretic Peptide in Normal Children and Children with Congestive Heart Failure / 实用儿科临床杂志

Objective To determine the normal ranges of N-terminal pro-brain natriuretic peptide(NT-proBNP) in normal children and children with symptoms of heart failure(HF),and to study their clinical implications.Methods Concentrations of serum NT-proBNP were determined in 80 normal children and 70 children with clinical symptoms of HF.Venous blood was taken in each subject,and plasma NT-proBNP was determined by ELISA method.Eighty normal children included 40 boys and 40 girls.Their ages ranged from 1 to 16 years old.Seventy children with HF were divided into two groups.The first group(n=45,21 males,24 females) included children with symptoms of HF caused by dilated cardiomyopathy(DCM).Their ages ranged from 1 to 16 years,and they had a left ventricular ejection fraction(LVEF) of less than 50%.The second group(n=25,11 male,14 female) consisted of children with symptoms of HF due to ventricular septal defect(VSD).Their ages ranged from 1 to 16 years,and they had an LVEF of 51%-78%.The serum NT-pro BNP levels were determined by ELISA method and LVEF was measured by echocardiography and clinical symptom score of heart failure was defined by using Ross Score.Results Serum concentration of NT-proBNP was 223.05 fmol/mL in normal children from 1 to 16 years old.NT-proBNP levels did not show a significant age-related or sex-related differences.In children with HF,the plasma NT-proBNP levels were significantly elevated(mean:1353.3 fmol/mL) compared to normal children(t=8.964 P

A novel KCNQ1 mutation in Chinese with congenital long QT syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>Congenital long QT syndrome (LQTS) is an inherited disorder of cardiac repolarization characterized by prolongation of QT interval and polymorphic ventricular tachycardia torsade de pointes (TdP) in the electrocardiogram (ECG). Clinical symptoms include recurrent syncope, seizure or even sudden death. It is caused by mutations of at least seven genes, six of them encoding ion channels that determine the duration of ventricular action potentials. One of these genes, KCNQ1, encodes an alpha-subunit of cardiac slowly activated delayed rectifier potassium channel. Patients carrying mutations of KCNQ1 are named as LQT1, which accounts for 42% of patients with LQTS. This study sought to analyze the clinical data of Chinese with LQTS and to screen for the mutations of KCNQ1.</p><p><b>METHODS</b>The universally accepted phenotypic criteria of LQTS was used for identification of probands. There were six families with LQTS. They were enrolled in this study. Clinical and ECG data of each family member were recorded. Genomic DNA was prepared from peripheral blood lymphocytes. Polymerase chain reaction-single strand conformation polymorphism analysis was used to screen for mutations throughout the whole coding region of KCNQ1 and DNA sequencing was performed to determine the exact mutation site.</p><p><b>RESULTS</b>There were totally 13 patients in the six LQTS families. Five were male and eight female. One suffered from sudden death, 10 had syncope and 2 were asymptomatic. Eleven of the 13 patients had ECG data. Their QT and QTc (mean +/- SD) were (0.460 +/- 0.058) s and (0.516 +/- 0.058) s, respectively. TdP was observed in 3 patients (27%) during the syncope attack. By PCR-SSCP analysis, two novel KCNQ1 deletion mutations 356-357 Delta QQ and 626-631 Delta GSGGPP were identified in 7 patients of 2 families. None of 50 normal individuals carried these mutations, indicating these two mutations were likely to cause the disease. In addition, P448R was found in one affected and some unaffected members in other two families and in 7 of 50 (14%) normal individuals, indicating that this might be a polymorphism. All the three mutations located in C-terminal domain of KCNQ1 protein.</p><p><b>CONCLUSIONS</b>Two novel deletion mutations and one novel polymorphism of KCNQ1 gene were identified among 6 Chinese families with LQTS.</p>

Research Progress of Gene Polymorphism Related with Kawasaki Disease / 实用儿科临床杂志

The pathogen of Kawasaki disease(KD) is still unknown although infection is considered as the most possibility factor.However epidemiologic studies showed that genetic background might be a main factor in the onset of KD.The recent papers on gene polymorphism including angiotensin-convertion enzyme,nitric oxide synthase and cytokine related with KD were searched and analyzed in this review.

Clinical Features and Prognosis of Neonatal Arrhythmias / 实用儿科临床杂志

Objective To explore the clinical features and prognosis of arrhythmia in newborn infants.Methods Eighty children with arrhythmia were diagnosed by physical examination and electrocardiogram monitoring in author's hospital from Jan.2004 to Dec.2006.Their clinical features and 24-hour dynamic electrocardiogram were analyzed at the acute stage and followed up.Results Out of 80 cases of arrhythimics,52 cases were boys and 28 cases were girls,with an average age of 4 days on diagnosis of arrhythmias.Forty-five neonates presented with supraventricular arrhythmia,accounting for 56.3%.Their clinical presentations were atypical,and the hypoxia,infection,electrolyte disturbances and metabolic disorders were the main causes of the arrhythmias.After supportive and anti-arrhythmia treatment,18 cases of arrhythmias disappeared of 25 children with premature atrial beats;10 cases of 21 children with premature ventricular beats were cured,2 cases of 4 children with ventricular tachycardia,1 case died;2 cases of 3 children with supraventricular tachycardia didn't occure;3 cases of 5 with atrio-ventricular block were cured.The prognosis was better in supraventricular arrhythmias than that in ventricular and other arrhythmias at discharge.At the follow-up of(1.2?0.7)years,there were no differences in rates of recovery between supraventricular arrhythmias and ventricular arrhythmias.Conclusions Supraventricular arrhythmia was the most common type of arrhythmias in neonates.Most of the arrhythmia in neonates might be functional and could recover without treatment.Supraventricular arrhythmia usually had better prognosis in acute period.Only a few neonates with severe arrhythmia need anti-arrhythmias treatment.