Immunological Abnormalities in Kawasaki Disease with Coronary Artery Lesions

A review of our previous immunological studies on Kawasaki disease (KD) was undertaken. The results showed that peripheral blood macrophages/monocytes, T-cells and B-cells become activated during acute KD in terms of numerical changes in immunocompetent cells, expression of activated antigens on the cell surfaces and cytokine production. Also, during acute KD with coronary artery lesions (CALs) the numbers of macrophages/monocytes are increased. In addition, both the increased levels of tumor necrosis factor-α and shed intercellular adhesion molecule-1 in serum are more evident in KD patients with CALs than in those without. Our results further suggest that the main characteristics of the pathogenesis of KD are increased numbers of peripheral blood macrophages/monocytes with the secretion of monokines by these activated cells, and the expression of adhesion molecules on immunocompetent cells. These immune responses develop more vigorously in KD patients with CALs.     

Successful Use of Low Molecular Weight Heparin in Intracardiac Thrombus of an Extremely Low Birth Weight Infant

The sick premature infants have high risk for thrombosis. Although therapeutic options include close observation, anticoagulation, thrombolytic therapy, and thrombectomy, guidelines for the management of neonatal arterial and venous thrombosis vary greatly among different centers. The authors report their experience using low molecular weight heparin (enoxaparin), with safe and successful resolution of right atrial thrombus, in an extremely low birth weight infant.     

冠状动脉造影在川崎病冠状动脉损害检查中的作用

目的　通过对疑有冠状动脉损害川崎病 (KD) 1 2例患儿行经皮冠状动脉造影 ,旨在准确了解冠状动脉损害情况 ,以指导临床对KD患儿的后期治疗及管理。方法　在静脉麻醉下采用Sedinger法穿刺右股动脉 ,采用Judkin法将冠状动脉造影管送达冠状动脉口 ,推注非离子造影剂 ,同时行电影摄影记录。结果　接受冠状动脉造影检查 1 2例患儿中 9例冠状动脉异常 ,其中左冠状动脉和 (或 )其分支受累 5例 ,右冠状动受累、左右冠状动脉同时受累各 2例。与超声心动图结果不尽一致。结论　冠状动脉造影可明确显示冠状动脉损害位置、形状、数目及病变程度 ,是一种安全、有效的检查方法。     

Multidetector Row Computed Tomography for Follow-Up of Patients with Coronary Artery Aneurysms Due to Kawasaki Disease

Multidetector row computed tomography (MDCT) coronary angiography was performed using a 16-slice MDCT scanner in three children with coronary aneurysms due to Kawasaki disease. Patients were given a -blocker. Following contrast injection, all data were acquired during a 20-second breathhold. Results were compared with those of conventional coronary angiography performed previously. MDCT provided clear visualization of coronary artery aneurysms, with coronary calcifications but which had not yet progressed to stenotic lesions. Because MDCT allows noninvasive detection and exclusion of coronary obstructions, it may be able to replace repeat conventional angiography as a follow-up study for children with coronary artery disease.     

Studies on the Effect of Long-Term Use of Low Dose Aspirin in Kawasaki Disease

The inhibitory action of long-term low dose aspirin (1–2 mg/kg/day for over 10 months) on the cyclooxygenase pathway in platelets and vascular endothe-lium was evaluated in 10 patients with Kawasaki disease. The results were compared with those obtained after taking aspirin at 5–10 mg/kg/day during the acute phase of the illness. Platelet aggregations induced by adenosinedi-phosphate (ADP), epinephrine and collagen were inhibited by aspirin doses of 1–2 and 5–10 mg/kg/day, when compared with those of controls (p < 0.05). Platelet synthesis of thromboxane B₂ (TXB₂) under doses of 1–2 and 5–10 mg/kg/day was 0.57 ± 0.07 and 0.72 ± 0.09 ng/ml platelet-rich plasma (PRP) /10⁵ platelets, respectively (p > 0.1). These values were significantly lower than those of the control group (22.88± 3.42 ng/ml PRP/10⁵ platelets) (p < 0.05). No differences were found in platelet aggregation and TXB₂ productivity between the two aspirin doses. Levels of 6 keto-prostaglandin F₁α (6k-PGF₁α) in platelet-poor plasma (PPP) did not differ significantly in these 3 sets of data. The results indicate that long-term administration of low dose aspirin (1–2 mg/kg/day) inhibits platelet aggregation by inhibiting synthesis of thromboxane A₂ (TXA₂), without interfering with prostacyclin production probably in the endothelium of blood vessels.     

Epidemiology and Risk Factors for Coronary Artery Abnormalities in Children With Complete and Incomplete Kawasaki Disease During a 10-Year Period

Kawasaki disease (KD) is an acute systemic vasculitis of childhood. The diagnosis is based on clinical criteria. However, the presentation of KD is incomplete/atypical for approximately 20 % of patients. Kawasaki disease is complicated with coronary artery lesions (CALs) and considered the most common cause of acquired heart disease in children. The medical records of children discharged with KD from a tertiary pediatric hospital in Athens, Greece, during a decade (2001–2010) were retrospectively analyzed. During the study period, KD was diagnosed for 86 children younger than 14 years of age. Complete diagnostic criteria were fulfilled by 64 of the children (74.4 %), whereas 25.6 % were considered incomplete cases. Cardiovascular complications were detected in 48 children (55.8 %) and CALs in 28 children (32.6 %). The prevalence of CALs did not differ significantly between complete and incomplete/atypical KD (42.2 vs 4.5 %; P = 0.001). Logistic regression analysis showed that erythema in the lips and oral cavity was associated with the development of CALs [odds ratio (OR), 3.03; 95 % confidence interval (CI), 1.051–8.783; P = 0.040]. Conversely, children with incomplete/atypical KD (OR, 0.092; 95 % CI, 0.010–0.816; P = 0.032) and previous antibiotic treatment (OR, 0.17; 95 % CI, 0.036–0.875; P = 0.034) were less likely to experience CALs. Children with an incomplete/atypical presentation of KD or before antibiotic treatment may be at lower risk for the development of CALs. Future multicenter studies may help to establish this association better.     

Follow-Up Chest X-Ray in Patients with Kawasaki Disease: The Significance and Clinical Application of Coronary Artery Macro-Calcification

Kawasaki disease (KD) related coronary artery (CA) aneurysms may lead to significant and potentially insidious progressive stenosis. It is also well recognized that CA scarring leads to heavy calcification in KD. We intended to correlate the angiographic anomalies associated with coronary calcifications in KD and to evaluate the chronology and the detection rate of KD-related CA calcification on plain chest X-ray. Between 1992 and 2006, 65 CA angiograms were performed in 50 KD patients. Chest fluoroscopies and angiograms were retrospectively reviewed. When angiograms were abnormal, chest X-rays were reviewed by two radiologists blinded to the results of angiograms. CA lesions were identified in 18/50 (36%) patients, including isolated CA aneurysms in 10. All 8 patients who had CA aneurysms associated with stenosis and/or occlusion had CA calcification identifiable on chest X-ray. All significant stenotic lesions were concomitant with calcification. Plain chest X-ray, a simple inexpensive low dose mean, easily identifies KD patients at risk for serious CA stenosis when specific search for CA calcification is pursued. When detected, a closer tracking of coronary artery patency is warranted via other imaging techniques, usually expensive, invasive, requiring sedation in children or exposing to high radiation.     

Plasma Clusterin Levels in Predicting the Occurrence of Coronary Artery Lesions in Patients With Kawasaki Disease

Kawasaki disease (KD) is the leading cause of acquired heart disease during childhood in the developed countries. Coronary artery lesions (CAL) are the major complications of KD. A unique proteomic profiling with increased or decreased fibrinogen, alpha-1-antitrypsin, clusterin, and immunoglobulin free light chains were noted in KD in our previous study. The purpose of this study was to evaluate relations between these biomarkers and CAL in KD and to establish within the markers the appropriate cut-off value with which to predict the occurrence of CAL. A total of 47 KD patients were enrolled, including 14 with CAL and 33 without CAL. Plasma samples from patients with KD before intravenous immunoglobulin administration were indicated for measurement of these biomarkers. A potential relation among CAL, clinical characteristics, and these biomarkers was investigated, and a receiver operating characteristic curve was used to identify a cut-off value of the significant marker that best predicated the occurrence of CAL. Among these biomarkers, only plasma clusterin level was associated with the occurrence of CAL. Using a cut-off value of clusterin <12.0 mg/l, the relative risk for CAL was 4.53-fold (95% confidence interval [CI] 1.060–19.347%, P = 0.014). Results from this study suggest that plasma clusterin level <12.0 mg/l in KD is significantly associated with the occurrence of CAL. Results from this study provide a potential biomarker of KD that may help predict the occurrence of CAL.     

Clinical Relevance of the Risk Factors for Coronary Artery Inflammation in Kawasaki Disease

The objective of this study was to determine predictive factors in children with Kawasaki disease (KD) with which we could distinguish the patients with KD who are either at very low risk or at very high risk for coronary artery inflammation (i.e., either patients who do not need intravenous immunoglobulin treatment or patients in whom more aggressive or even experimental therapies should be considered). Prospectively collected demographic, clinical, and laboratory data on 344 patients treated for KD were correlated with the patients' echocardiographic findings. The parameters studied were age, sex, duration of the fever, erythrocyte sedimentation rate, hemoglobin, white blood cell count, platelet count, and serum albumin. These were examined both in bivariable comparisons and in multiple logistic regression models. Low serum albumin, age <1 year, and the duration of the fever prior to treatment were risk factors for coronary arteritis. In the multivariable models, their combined predictive value for coronary lesions was poor, especially when identifying the patients at a low risk for coronary artery lesions (CALs). In fact, 44 of 98 patients with CALs were falsely classified to the low-risk group. Ten of 14 patients younger than 1 year of age, who also had low serum albumin (<30 g/L), had echocardiographically verified CALs, and 7 (50%) had a definite coronary artery aneurysm. We could not distinguish a group at such a low risk that these patients could be left untreated. Young patients with low albumin run a very high risk for CALs.     

Intravascular Ultrasonography of an Adolescent Boy with a Coronary Artery Aneurysm Due to Kawasaki Disease

A 14-year-old boy developed coronary aneurysms during the course of Kawasaki disease. The vessel wall morphology of the coronary arteries was assessed by intravascular ultrasound imaging (IVUS). There was intimal thickening proximal to, within, and distal to a large coronary aneurysm in the left anterior descending coronary artery only 18 months after the acute onset of Kawasaki disease. Intimal thickening without calcification is a new IVUS finding within a persistent coronary aneurysm. It may indicate that the healing process, via cell proliferation is continuing, with the risk of causing a stenosis.     

平板运动试验评价川崎病并冠状动脉损害32例

目的评价平板运动试验对川崎病(KD)并冠状动脉损害的诊断价值。方法采用美国GE公司生产的T2100活动平板对本院2008年4月-2009年4月诊断为KD且存在冠状动脉损害的32例患儿进行平板运动试验。男27例,女5例;年龄4.5～14.0岁。均符合KD诊断标准,超声心动图均提示存在冠状动脉损害。结果32例患儿除2例出现严重面色苍白,体力不支不能耐受外,余30例均出现不同程度的ST段改变:其中出现ST段改变达到阳性标准14例;出现ST段改变未达到阳性标准8例;出现收缩压下降≥10mmHg(1mmHg=0.133kPa)5例;出现典型心绞痛3例。且ST段改变与冠状动脉病变程度高度相关。结论平板运动试验用于KD并冠状动脉损害患儿的随访与诊断,可重复多次检查,是一种安全可行的评价冠状动脉病变的非侵入性检查方法。     

Severe Coronary Artery Disease in the Absence of Supravalvular Stenosis in a Patient with Williams Syndrome

Williams syndrome is a complex syndrome comprising developmental abnormalities, craniofacial dysmorphic features, and cardiac anomalies. The most common cardiac anomaly is supravalvular aortic stenosis. We report a case of a 6-year-old girl with Williams syndrome who presented with decompensated heart failure due to ischemic cardiomyopathy. Her only significant cardiac anomaly was severe stenosis of the left main coronary artery. She subsequently died despite surgical revascularization. Isolated coronary anomalies are rare in Williams syndrome but should be considered especially in the presence of heart failure or ischemia.     

低分子质量肝素联合更昔洛韦体外抗人巨细胞病毒的作用

目的 研究低分子质量肝素(LMWH)联合更昔洛韦(GCV)体外抗人巨细胞病毒(HCMV)感染的作用.方法 采用四甲基偶氮唑盐(MTT)比色法测定LMWH联合GCV对人胚肺成纤维细胞(HELF)的最大无毒质量浓度(TC0).应用体外细胞培养技术建立HCMV-AD169感染HELF模型.固定联合药物中LMWH的TC0(625.00 mg·L-1),设LWMH 625.00 mg·L-1、GCV 35.00 mg·L-1、GCV 17.50 mg·L-1、GCV 8.75 mg·L-1、LMWH 625.00 mg·L-1+ GCV 35.00 mg·L-1、LMWH 625.00 mg·L-1+ GCV 17.50 mg·L-1、LMWH 625.00 mg·L-1+ GCV 8.75 mg·L-1 7个不同用药组,分别干预HCMV感染细胞模型,使用MTT法检测各组细胞存活率,观察感染细胞特征性细胞病变(CPE),同时应用荧光定量PCR法检测用药后各组HCMV的载量.结果 联合药物的TC0中GCV的质量浓度为375.00 mg·L-1,LMWH的质量浓度为625.00 mg·L-1.当HCMV AD169浓度为100倍半数组织培养感染量(TCID50)感染HELF时,LMWH和GCV均可提高受染细胞存活率,降低受染细胞的HCMV DNA的拷贝数;当固定LMWH的TC0,与3种不同质量浓度GCV配伍时,均在HELF上有明显的抗HCMV的生物活性,并显示配伍后的抑制作用明显大于对应质量浓度单用GCV的抑制作用(P<0.01);当联合用药中GCV剂量减半时与全量应用GCV时的抗HCMV效果相同[即GCV 35.00 mg·L-1组与联合用药LMWH 625.00 mg·L-1+GCV 17.50 mg·L-1组的病毒抑制率和DNA拷贝数比较差异无统计学意义(P>0 05)];且联合用药对细胞的毒性试验结果及显微镜下观察细胞形态变化显示,随着联合用药中二者药物质量浓度的下降,细胞存活率升高,对细胞的毒性作用减弱.结论 LMWH联合GCV具有良好的体外抗HCMV作用,二者具有协同抗病毒作用.     

Age-Related Acceleration of Endothelial Dysfunction and Subclinical Atherosclerosis in Subjects with Coronary Artery Lesions After Kawasaki Disease

The objective of this study was to test the hypothesis that accelerated endothelial dysfunction and the development of premature atherosclerosis are associated with age in subjects with coronary artery lesions after Kawasaki disease (KD). A case-control study was performed at a university hospital that included 35 post-KD subjects across a wide age range (range, 8–42 years) without traditional cardiovascular risk factors and 35 age- and sex-matched healthy control subjects (Cont). Flow-mediated dilatation (FMD) of the brachial artery-induced by reactive hyperemia, intima media thickness (IMT), and elastic modulus (Ep) of the common carotid artery were compared between KD and Cont subjects assessed against age. KD subjects had slightly higher levels of body mass index, lipid profile, and HbA1c than Cont subjects, but the differences were not significant. The mean IMT (p < 0.001), age-adjusted percentage normal IMT (%N IMT; p < 0.0001), and Ep (p < 0.001) were significantly higher in KD than Cont subjects, and the peak FMD% (p < 0.01) was significantly lower in KD than Cont subjects. There were significant correlations between FMD% and age (r = −0.51 p < 0.0001), IMT and age (r = 0.68, p < 0.001), and Ep and age (r = 0.58, p < 0.01) in KD but not Cont subjects. When the difference in FMD% between KD and matched Cont subjects (ΔFMD%) was plotted against age, no significant relationship was found, although significant correlations between ΔIMT and age (r = 0.52, p < 0.01) as well as between ΔEp and age (r = 0.46, p < 0.05) were observed. When we defined values that were +2.0 SD over the mean control values (i.e., %N IMT ≥ 120% and/or Ep ≥ 50 kPa) as markers of subclinical atherosclerosis, 15 subjects met the criteria. Subjects over the age of 22 years were more likely to have (OR = 16.54, p = 0.0001) subclinical atherosclerosis in this cohort. Our results suggest that endothelial dysfunction and the development of premature atherosclerosis were accelerated in adult post-KD compared to Cont subjects.     

Evaluation of Preclinical Atherosclerosis by Flow-Mediated Dilatation of the Brachial Artery and Carotid Artery Analysis in Patients with a History of Kawasaki Disease

Cardiac sequelae of Kawasaki disease are an important cause of ischemic heart disease in young adults. The possibility of early progression of atherosclerosis following Kawasaki disease is therefore of great concern. We examined whether preclinical atherosclerotic changes are seen in patients with a history of Kawasaki disease, and whether these changes appear in all or in only a proportion of patients. Sixty-five patients with a history of Kawasaki disease, aged 13.1 ± 2.1 years, and 20 aged-matched controls participated in the study. All subjects underwent flow-mediated dilatation (FMD) of the brachial artery and analysis of carotid artery size and pulse-wave transmission. Patients were classified into four groups depending on the severity of the maximum coronary artery lesion: group 0 (normal), group 1 (mild), group 2 (moderate), and group 3 (severe). There was no statistical difference in the carotid artery analyses between the four groups. FMD (mean ± SD) was significantly lower in groups 2 and 3 than in groups 0 and 1 and the control group (group 0, 19.4 ± 3.9%; group 1, 19.5 ±4.1%; group 2, 8.9 ± 2.8%; group 3, 4.2 ± 1.5%; control group, 18.8 ± 2.8%; p < 0.0001). There was a significantly negative correlation between the severity of the coronary artery lesion and FMD (p < 0.0001 for both). Endothelial dysfunction was revealed by FMD in patients with persistent coronary artery lesions subsequent to Kawasaki disease. Preclinical atherosclerosis may be present only in patients with coronary aneurysms.     

内皮细胞型一氧化氮合酶基因多态性与川崎病冠状动脉损伤易感性的相关性

目的 探讨内皮细胞型一氧化氯合酶(eNOS)基因第4内含子a/b和第7外显子G894T多态性与儿童川崎病(KD)发病及并冠状动脉损伤(CAL)的相关性.方法 选择住院KD患儿69例(KD组),其中CAL 39例(CAL组),无冠状动脉损伤(NCA)30例(NCA组).同期选择健康体检儿童90例作为健康对照组.采用PCR方法 和聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术检测各组基因型与等位基因频率.结果 KD组和健康对照组eNOS基因内含子4基因型aa加ab:bb分布分别为0.30∶0.70和0.32∶0.68;等位基因a∶b频率分别为0.18∶0.82和0.17∶0.83,二组基因型及等位基因频率比较均无显著性差异(Pa>0.05),KD CAL组与NCA组基因型aa加ab:bb分布分别为0.33∶0.67和0.30∶0.70;二种等位基因a∶b频率分别为0.15∶0.85和0.19∶0.81,二组基因型及等位基因频率比较均无显著性差异(Pa>0.05).KD组eNOS基因第7外显子G894T基因型GT:GG频率显著高于健康对照组(0.26∶0.74 vs 0.13∶0.87 P<0.05),KD组T等位基因频率较健康对照组高,但无统计学意义(0.19 vs0.17 P>0.05),KD CAL组和NCA组GT基因型及T等位基因频率比较差异均无统计学意义(0.26 vs 0.20,0.83 vs 0.79 Pa>0.05).危险度分析结果 为GT基因型的个体患KD的风险是健康对照组的1.96倍,其差异有统计学意义(OR=1.96,95%GI1.086～4.481 P=0.048);eNOS基因4a/b各基因型与KD发病无明显相关性(OR=0.92,95%CI 0.468～1.811 P=0.864).结论 eNOS基因第7外显子G894T多态性的GT基因型可能与KD发病有关,第4内含子a/b及第7外显子G894T多态性与KD CAL可能无关.     

Percutaneous Transluminal Coronary Angioplasty for Coronary Arterial Stenosis in a 10-Year-Old Boy with Kawasaki Disease and a Brief Review

A 10-year-old boy developed coronary artery stenosis 9 years after suffering Kawasaki disease with coronary artery aneurysms at the age of 7 months old. Percutaneous transluminal coronary angioplasty was performed successfully to dilate the coronary arteries in order to prevent obstruction of the coronary arteries.