Retrograde holodiastolic flow in the abdominal aorta detected by pulsed Doppler echocardiography in patients with Kawasaki disease

Retrograde holodiastolic flow in the abdominal aorta (retrograde flow) detected by pulsed Doppler echocardiography is usually noted in patients with aortic regurgitation or patent ductus arteriosus. Similar abnormal flow often is present in patients with acute phase Kawasaki Disease (KD). In 21 patients with acute phase KD, 15 had a retrograde flow. Retrograde flow was recognised in only 3 of patients with acute infection (n=31) and in no healthy controls (n=10). The ratio of the time velocity integral for diastolic retrograde flow to that for antegrade flow (regurgitant fraction) was significantly greater in patients with KD (median value 23%) than in patients with acute infection (1%) or healthy individuals (1%) (P < 0.001 for both). Four patients with coronary arterial involvement (one with an aneurysm and three with transient dilation of the coronary arteries) had a greater regurgitant fraction than the 17 patients without coronary arterial involvement (median values: 31% versus 18%, P < 0.05). The C-reactive protein was increased for a longer period of time in patients with KD with a greater regurgitant fraction (P < 0.01). Plasma nitric oxide (NO) metabolite concentrations were significantly greater in patients with KD than in those with acute infection or in healthy controls (P < 0.001 for both). There was a positive correlation between plasma NO metabolite concentrations and the regurgitant fraction in patients with KD (r=0.69). Conclusion Retrograde flow in the abdominal aorta is increased in patients with Kawasaki disease. Further studies are needed to clarify the causal relationship between the abnormal flow and the overproduction of nitric oxide. Received: 16 March 1999 / Accepted: 12 January 2000     

Water retention in the acute phase of Kawasaki disease: relationship between oedema and the development of coronary arterial lesions

Despite intravenous immunoglobulin therapy, a certain percentage of patients with Kawasaki disease (KD) still develop coronary arterial lesions (CAL). In an effort to find new combined therapies to reduce the incidence of CAL, we focused on the oedema which can be an important sign of the increased vascular permeability in KD. A total of 127 patients with KD were included in the retrospective study. Serial weekly changes in serum sodium and albumin levels from the 1st to the 4th week of illness were examined. In addition, the maximum rate of increase in body weight from admission to the 14th day of illness was evaluated. Serum sodium levels (mEq/l) in only the 2nd week of illness were significantly lower in patients with CAL than in those without CAL (mean ± SD, 135.5±4.5 versus 138.0±2.4, P <0.05). Serum albumin levels in all 4 weeks were significantly lower in patients with CAL than in those without CAL ( P <0.001). The maximum rate (%) of increase in body weight from admission to the 14th day of illness was significantly higher in patients with CAL than in those without CAL (ranges and median values, 0–12.3 (7.0) versus 0–10.3 (3.2), P <0.001). Conclusion:these results suggest that water retention in the acute phase of Kawasaki disease may be a risk factor for CAL, and water intake of both infusion and oral intake should be kept to a minimum in order to avoid progressive oedema.Abbreviations ASA acetylsalicylic acid - CAL coronary arterial lesions - HGF hepatocyte growth factor - IVIG intravenous immunoglobulin - KD Kawasaki disease - MBW maximum rate of increase in body weight - VEGF vascular endothelial growth factor     

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.     

川崎病患儿血清抗内皮细胞抗体和抗中性粒细胞胞浆抗体检测的临床意义

目的 探讨抗内皮细胞抗体（AECA）和抗中性粒细胞胞浆抗体（ANCA）在川崎病（KD）及其冠状动脉损害（CAL）中的临床意义。方法 应用酶联免疫吸附试验定量检测42 例KD 患儿急性期、缓解期血清AECA 和ANCA 水平,并行心脏超声心动图了解CAL 发生情况。随机选取20 例因呼吸道感染发热患儿和15 例外科择期手术患儿分别作为发热对照组和普通对照组。结果 急性期KD 组AECA、ANCA 水平均显著高于两对照组（PPPPr=0.88,P结论 AECA、ANCA 可能参与了KD 血管炎及其CAL 的发生。急性期血清AECA、ANCA 对早期难以确诊的KD 有参考价值,ANCA 水平异常增高对CAL 有一定的预警价值。     

Increased nitric oxide production by neutrophils in early stage of Kawasaki disease

Recent observations suggested that nitric oxide (NO) has a role in triggering the early endothelial dysfunction in Kawasaki disease (KD). We investigated the amount of NO in conjunction with reactive oxygen species (ROS) produced by neutrophils in children with acute KD by a newly developed flow cytometric analysis. Forty children with acute KD (n = 14), non-KD febrile disease (n = 14), and afebrile control (n = 12) were enrolled (age, 3 to 88 months). Neutrophils in KD produced significantly higher amount of NO compared to others (p < 0.05). With regard to ROS, significant increase was not only found in KD but also in non-KD febrile children (p < 0.05 and p < 0.01, respectively). In KD patients, the amount of NO produced by neutrophils decreased after immunoglobulin (IVIG) treatment, while there was no significant change in ROS production. The amount of NO in KD patients also correlated well with the days from the onset. One patient who developed coronary arterial lesion showed the highest value of NO. In conclusion, neutrophils in acute KD generate both NO and ROS considerably, while NO production is exclusive in the early stage of KD before IVIG treatment. Abnormal immune system in KD might be characterized by an overproduction of NO, whereas the role of NO in endothelial damage remains to be elucidated.     

Coronary artery lesions of incomplete Kawasaki disease: a nationwide survey in Japan

Incomplete Kawasaki disease (KD) is associated with delayed diagnosis and treatment, which in turn can lead to the development of coronary artery lesions (CALs). The aim of this study was to determine the epidemiological features of incomplete KD compared with complete KD and to identify risk factors for CALs from incomplete KD patients using data from a nationwide survey of 2007–2008 in Japan. A total of 23,263 patients were classified according to the number of principal clinical signs: 80% (n = 18,620) had complete forms of KD, 14.2% had four principal signs, 4.6% had three signs, and 1.2% had only one or two signs. In comparison with complete KD cases, the prevalence of CAL development tended to be larger and the proportion receiving initial intravenous immunoglobulin (IVIG) treatment were significantly smaller in patients with incomplete forms. In addition, hospital attendance after 7 days of illness or later was significantly associated with CAL development in all incomplete groups (OR: 2.52 in total patients with incomplete KD, 3.26 in those with one or two principal signs, 2.94 in those with three signs, 2.35 in those with four signs). Conclusion The higher prevalence of CALs in incomplete KD reflects difficulties in diagnosis and delays in treatment. More timely diagnosis and treatment of incomplete KD patients could further prevent the development of cardiac lesions.     

The number and function of circulating endothelial progenitor cells in patients with Kawasaki disease

Kawasaki disease (KD) is associated with coronary artery injury. Studies have shown that the endothelial progenitor cell (EPC) participates in the process of arterial repair. Data have been reported that the number of EPC increased significantly in the subacute phase of KD. However, until now, there are no data about the functions of EPC in KD patients. The present study was designed to further investigate the number and functions of EPC in KD. Ten KD patients in the acute phase and ten healthy volunteers were recruited and attributed to the KD group and control group, respectively. The circulating CD34/kinase insert domain-containing receptor double positive cells were evaluated in the two groups using flow cytometry. In vitro assays were used to measure the functions of EPC, including proliferation, adhesion, and migration activities. The plasma levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP) were also assessed in both groups. The number of EPC in the KD group was significantly higher than that of the control group (0.021 ± 0.007% vs. 0.014 ± 0.003%, P < 0.05). The migratory response of EPC was significantly decreased in the KD group, compared with that of the control group (5.50 ± 1.78 vs. 3.40 ± 1.35 cells/high power field, P < 0.01). Similarly, the proliferative and adhesive activities of EPC in the KD group were also decreased (0.47 ± 0.08 vs. 0.66 ± 0.07, P < 0.01; 6.5 ± 2.12 vs. 11.2 ± 2.04 cells/high power field, P < 0.01). The plasma NO, TNF-α, and hs-CRP levels in the KD group were higher than those of the control group (54.10 ± 11.78 vs. 38.80 ± 11.10 μmol/l, P < 0.01; 48.20 ± 7.42 vs. 37.00 ± 11.12 pg/ml, P < 0.05; 87.10 ± 30.18 vs. 5.30 ± 3.37 mg/l, P < 0.01). The number of circulating EPC positively correlated with the level of NO (r = 0.92, P < 0.001), and the functions of EPC negatively correlated with the levels of TNF-α and hs-CRP, respectively. In Kawasaki disease, the number of EPC was enhanced and the functions of EPC were attenuated. The two-way regulation of circulating EPC in KD patients may be associated with the disorders of cytokines or messengers in KD patients.     

Programmed death-1 (PD-1) gene polymorphisms lodged in the genetic predispositions of Kawasaki Disease

The purpose of this study is to investigate the association of programmed death-1 gene (PD-1) polymorphisms with genetic predispositions to Kawasaki disease (KD). A total of 73 patients with KD and 100 healthy controls were enrolled from 2007 to 2008. Two single nucleotide polymorphisms of the PD-1 gene, rs41386349 and rs2227981, were analyzed. Higher T allele frequency of rs41386349 was found in the patient group than the control group (p = 0.007, odds ratio (OR) = 1.9, 95% CI = 1.2–2.9). PD-1 rs2227981 polymorphism was not significant in patients with KD comparing with the control group (p = 0.4, OR = 1.2 (0.8–1.9)). Furthermore, no difference of PD-1 polymorphisms between patients with coronary artery dilatation (CAD) and those without CAD was found. Our data support the possibility that PD-1 gene polymorphism may be related with the genetic susceptibility of KD in Korean population.     

Lack of an association between E‐selectin gene polymorphisms and risk of Kawasaki disease

Background: Coronary artery lesions (CAL) are a serious complication of Kawasaki disease (KD). The increased serum E‐selectin level during the acute phase of KD and the association of E‐selectin gene (SELE) polymorphisms with the prevalence of coronary artery disease in adults suggest a possible association between SELE polymorphisms and the development of CAL in KD patients. Methods: The subjects consisted of 177 KD patients, including 59 with and 118 without CAL, and 305 healthy controls. Two single nucleotide polymorphisms (SNP) of SELE, 98G>T (rs1805193) and Ser128Arg (rs5361), were genotyped by direct sequencing and the high‐resolution melting curve method, respectively. The allele distributions were assessed using the chi‐squared test. Results: There were no significant differences in the T allele frequency at 98G>T between KD patients and controls (1.4% vs 1.0%, P= 0.55) or between KD patients with and without CAL (1.7% vs 1.3%, P= 0.77). Similarly, there were no differences in the distribution of the C allele (128Arg) at Ser128Arg between KD patients and controls (4.5% vs 3.4%, P= 0.40) or between KD patients with and without CAL (4.2% vs 4.7%, P= 0.86). Conclusion: Although no association was detected between these SELE polymorphisms and the prevalence of KD or the development of CAL, this may have been due to the study limitations, including a low frequency of the minor alleles and a small sample size. A larger‐scale association study is needed in order for a definitive conclusion to be made as to whether these SNP are associated with susceptibility to KD or not.     

Prediction of the Risk of Coronary Arterial Lesions in Kawasaki Disease by Brain Natriuretic Peptide

Kawasaki disease (KD) is an acute systemic vasculitis associated with the development of coronary arterial lesions (CALs) occurring in 3–5% of children treated by intravenous immune globulin (IVIG). However, a considerable number of patients who are not responding to IVIG are at much higher risk. Although studies have explored potential biomarkers to predict patients with KD who are at risk of CAL, no useful single marker exists. We hypothesized that the serum concentrations of the N-terminal moiety of brain natriuretic peptide (NT-proBNP) can be useful to predict CAL. Forty-three children with KD (29 males and 14 females) were enrolled in this study. Despite IVIG, 6 of the 43 patients developed CAL. There were, however, no significant differences in variables between children with CAL and those without CAL: These include age, gender, day of the illness, leukocyte count, and the serum levels of sodium, C-reactive protein, and albumin. The serum NT-proBNP level was significantly higher in children with CAL than those without CAL (2,611 ± 1,699 vs. 1,073 ± 1,427 pg/ml; P = 0.03): the cutoff value of 1,000 pg/ml to predict CAL produced a specificity of 0.68, sensitivity of 0.83, and an odds ratio as high as 10.4. In conclusion, NT-proBNP is increased in KD patients who are developing CAL, and patients with an elevated serum NT-proBNP >1,000 pg/ml have a risk of CAL ~10 times higher than that of patients with a modest increase.     

川崎病患儿恢复期血管内皮功能与急性期C-反应蛋白关系

目的 探索性研究川崎病（KD）患儿恢复期外周血管内皮功能与急性期血清C-反应蛋白(CRP)水平及冠状动脉损害（CAL）的关系,探讨外周血管内皮功能测定作为KD患儿血管内膜功能康复指标的可能性。方法 纳入复旦大学附属儿科医院（我院）心内科住院、具备完整的急性期临床资料、病程>2个月,并于我院心内科随访的KD患儿。采用EndoPat2000仪器测定外周血管内皮功能,记录反应性充血-外周动脉张力指数（RHI）。将血清CRP值转化为有序多分类资料进行分析,划分切点为第20、40、60、80和100百分位,分为5组。观察KD患儿RHI分布的特征。调整患儿年龄和性别后,分析RHI与急性期血清CRP的关系;比较发生和未发生CAL的KD患儿血清CRP和RHI水平的差异。结果 26例KD患儿进入本研究,男21例。平均年龄（83±24）个月,平均病程（27±17）个月。急性期CRP平均水平为91.9 mg·L-1。平均RHI为1.3 mL·mm-1 Hg×100。调整了年龄和BMI Z评分后,RHI与CRP呈负相关（R2= 0.411 9,Pmodel=0.025 3,b=-0.483,PCRP＝0.019）。发生CAL的KD患儿的RHI水平低于未发生CAL患儿,（1.04 ±1.10） vs （1.34 ±0.08） mL·mm-1 Hg×100,P=0.054,急性期的CRP水平在发生和未发生CAL的KD患儿间差异无统计学意义。结论 急性期CRP水平与KD恢复期外周血管内皮功能存在负相关,即CRP水平越高,内皮功能受损越严重;发生CAL患儿内皮功能损伤更严重。     

BTNL2 gene polymorphisms may be associated with susceptibility to Kawasaki disease and formation of coronary artery lesions in Taiwanese children

The butyrophilin-like 2 (BTNL2) gene is a member of the B7 receptor family that probably functions as a T cell costimulatory molecule. Because altered T cell functions are implicated in dysregulation of the immune response seen in Kawasaki disease (KD), it is reasonable to speculate that BTNL2 gene is involved in the pathophysiology of KD. The purpose of this study was to investigate whether polymorphisms of the BTNL2 gene are associated with KD and the development of coronary artery lesions (CALs) in Taiwanese children. Nine-three patients with KD and 669 ethnically matched healthy controls were genotyped for BTNL2 gene rs1555115 C/G and rs2395158 A/G polymorphisms. The frequency of GG genotype of rs 1555115 was significantly higher in KD patients compared with controls (2.2% vs 0.2%, P = 0.012). The odds ratio for developing KD in individuals with rs 1555115 GG genotype was 14.7 (95% confidence interval, 2.04–105.5, P = 0.003) compared with individuals with rs 1555115 CG and CC genotypes. No significant difference was observed in the genotype and allelic frequencies of rs 2395158 polymorphism between KD patients and controls. However, the frequency of the G allele of rs 2395158 was significantly higher in KD patients with CALs than in those without CALs (P = 0.001). No significant difference was observed in the genotype and allelic frequencies of rs 1555115 polymorphism between KD patients with and without CALs. In conclusion, our results suggest that BTNL2 gene polymorphisms might be genetic markers of KD susceptibility and risk of coronary artery complication in Taiwanese children.     

A meta-analysis on the effect of corticosteroid therapy in Kawasaki disease

The current recommended therapy for Kawasaki disease (KD) is the combination of intravenous immunoglobulin (IVIG) and aspirin. However, the role of corticosteroid therapy in KD remains controversial. Using meta-analysis, this study aimed to investigate the efficacy of corticosteroid therapy in KD by comparing it with standard IVIG and aspirin therapy. We included all related randomized and quasi-randomized controlled trials by searching Medline, the Cochrane Central Register of Controlled Trials, EMBASE, Pub Med, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, and the Japanese database (Japan Science and Technology) as well as hand searches of selected references. Data collection and meta-analysis were performed to evaluate the effect of corticosteroids. Our search yielded 11 studies; 7 of which evaluated the effect of corticosteroid for primary therapy in KD, and 4 investigated the effect of corticosteroid therapy in IVIG-resistant patients. Meta-analysis of these studies revealed a significant reduction in the rates of initial treatment failure among patients who received corticosteroid therapy in combination with IVIG compared to IVIG alone (odds ratio (OR) = 0.50; 95% CI, 0.32~0.79; p = 0.003). Furthermore, the use of corticosteroids reduced the duration of fever and the time required for C-reactive protein to return to normal. Our data did not show any significant increase in the incidence of coronary artery lesions or coronary aneurysms (OR = 0.67; 95% CI, 0.35~1.28; p = 0.23) in the corticosteroid group. Conclusion. Corticosteroid combined with IVIG in primary treatment or as treatment of IVIG-resistant patients improved clinical course without increasing coronary artery lesions in children with acute KD.     

Pulse methylprednisolone with gammaglobulin as an initial treatment for acute Kawasaki disease

Approximately 15–20% of patients with Kawasaki disease (KD) are not responsive to high-dose intravenous gammaglobulin (IVIG). We have previously reported a predictive method for identifying IVIG-non-responsive patients (high-risk KD patients). We determined the safety and effectiveness of pulse methylprednisolone with high-dose IVIG (mPSL+IVIG) as a primary treatment for high-risk KD patients. Sixty-two high-risk KD patients were treated with pulse methylprednisolone 30 mg/kg over 2 h, followed by IVIG 2 g/kg over 24 h (mPSL+IVIG group) and were compared with a historical control group of 32 high-risk patients treated with IVIG 2 g/kg alone at the participating hospitals before this study was opened (IVIG group). High-risk patients were identified with at least two of three predictors (C-reactive protein ≥7 mg/dL, total bilirubin ≥0.9 mg/dL or aspartate aminotransferase ≥200 IU/L). Sixty-six percent (95% confidence interval [CI] 54–78%) of patients had a prompt defervescence in the mPSL+IVIG group compared with 44% (95% CI 26–62%) for the IVIG group (p = 0.048). Coronary artery lesions were observed in 24.2% (95% CI 13.2–35.2%) and 46.9% (95% CI 28.6–65.2%) of patients in the mPSL+IVIG and IVIG groups, respectively (p = 0.025). This is the first report showing that mPSL+IVIG is effective and safe as a primary treatment for high-risk KD patients.     

Studies of Peripheral Blood Toxic Neutrophils as a Predictor of Coronary Risk in Kawasaki Disease—the Pathogenetic Role of Hematopoietic Colony-Stimulating Factors (GM-CSF, G-CSF)

Many toxic neutrophils, characterized by cytoplasmic swelling, vacuolization and toxic granulation, can be seen in the acute phase of Kawasaki Disease (KD; mucocutaneous lymph node syndrome). Polymorphonuclear neutrophils (PMNs) of 36 patients with acute and convalescent phase KD were studied with reference to their morphological characteristics. The percentage of toxic neutrophils in the acute phase tended to be higher in the group with coronary artery lesions (CAL) than in the group without CAL. The results suggest that observation of toxic neutrophils in the acute phase of KD may be useful in predicting a high risk of CAL. In vitro cultivation studies of PMNs from healthy persons, in the presence of diverse hematopoietic colony-stimulating factors (CSF), revealed that GM-CSF (granulocyte-macrophage-CSF) and G-CSF (granulocyte-CSF) participated in the induction of cytoplasmic vacuolization of PMNs, and that the healthy PMNs morphologically mimicked peripheral PMNs seen in the acute phase of KD.     

川崎病患儿血清基质金属蛋白酶-1表达的意义

目的 探讨基质金属蛋白酶-1(MMP-1)在川崎病(KD)患儿冠状动脉损伤中的作用.方法 选择KD患儿36例(其中无冠状动脉损伤组15例,冠状动脉损伤组21例),按病程分为急性期、亚急性期和恢复期;10例健康儿童为健康对照组.应用酶联免疫吸附法检测其血清MMP-1蛋白水平.结果 KD急性期患儿血清MMP-1水平明显高于健康对照组(Pa＜0.01),且冠状动脉损伤组较无冠状动脉损伤组升高更显著(P＜0.05);亚急性期、恢复期其MMP-1水平明显降低(各期间比较Pa＜0.01).KD组急性期血清MMP-1水平与外周血白细胞计数呈显著正相关(r＝0.791 P＜0.01).结论 检测血清MMP-1水平对预测和早期诊断KD并冠状动脉病变具有重要意义.     

川崎病患儿血清脂联素水平的变化

目的 探讨川崎病(Kawasaki disease, KD)患儿血清脂联素的变化及意义.方法 选取KD 患儿45 例,其中冠状动脉损伤(CAL)患儿18 例,未合并CAL 患儿27 例;另选取健康儿童20 例作为对照组.采用ELISA 法检测血清脂联素水平,全自动生化测定仪检测血脂四项,包括甘油三酯(TG)、胆固醇(TC)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C).结果 合并CAL 与未合并CAL 组急性期、亚急性期、恢复期血清脂联素水平均低于正常对照组(P<0.01);急性期与亚急性期其水平均低于恢复期(P<0.01).在急性期与恢复期,CAL 组血清脂联素水平显著高于未合并CAL 组(P<0.05).合并CAL 与未合并CAL 组血清TC、HDL、LDL 均较正常对照组降低(P<0.05).KD 患儿血清脂联素水平与TC、TG、CRP 水平及CAL 的发生呈明显正相关,r 分别为0.31、0.30、0.34、0.35,均P<0.05.结论 KD 患儿存在血脂紊乱及低脂联素水平;血清脂联素水平降低可能是全身炎症反应的结果;血清脂联素增加与CAL 的发生关系密切.     

川崎病合并冠状动脉损害的遗传学基础

川崎病（KD）主要危及生命的并发症是冠状动脉损害（CAL）,引起冠状动脉狭窄、血栓形成、动脉瘤破裂等,甚至猝死。KD现已成为儿童后天性心脏病的主要病因。因此,早期发现哪些KD患儿是发生CAL的易患人群,并予及时干预十分重要。遗传因素在KD及其CAL的发生发展中起重要作用,目前已发现多个基因的多态性与CAL相关。该文主要就近年来国内外关于KD合并CAL基因多态性的研究作一综述。     

Serum vascular endothelial growth factor: a new predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease

We investigated serum vascular endothelial growth factor (SVEGF) levels in Kawasaki disease and determined whether these levels had any association with the development of coronary artery lesions. We measured SVEGF levels in 66 patients with Kawasaki disease, 18 patients with active infections and 18 afebrile controls. SVEGF levels of patients in the acute phase of Kawasaki disease (0.0–2003.6 pg/ml, median 59.87 pg/ml) were significantly higher than those of patients with active infections (0.0–45.2 pg/ml, median 8.10 pg/ml; P < 0.05) or afebrile controls (0.0–49.8 pg/ml, median 7.75 pg/ml; P < 0.05) and decreased to undetectable or low levels in the recovery phase (n=31, acute phase: 0.0–2003.6 pg/ml, median 62.50 pg/ml versus recovery phase: 0.0–146.5 pg/ml, median 26.90 pg/ml; P=0.0007) of the disease. There existed a positive correlation between SVEGF levels and serum C-reactive protein concentrations in the acute phase of Kawasaki disease (r _s =0.347, P=0.0051). In addition, SVEGF level and duration of fever were found to be major risk factors for the occurrence of coronary artery lesions by univariate (P=0.012 and P=0.003, respectively) and multivariate (P=0.037, OR 6.16 and P=0.0059, OR 7.59, respectively) analyses. Conclusion Serum vascular endothelial growth factor level, in combination with persistence of fever, could be a powerful predictor for the development of coronary aneurysms. Received: 16 March 1999 / Accepted: 30 November 1999     

Immunohistochemical study of apparently intact coronary artery in a child after Kawasaki disease

BACKGROUND: Coronary arterial lesions (CAL) due to Kawasaki disease (KD) often show progressive intimal hyperplasia even many years after the disease. However, most patients have no CAL after the acute phase, and it is an important issue whether or not coronary arteries without CAL have significant intimal hyperplasia, and whether or not there is the potential for this to progress to stenosis and/or atherosclerosis. METHODS: The authors examined formalin-fixed specimens of the coronary arteries immunohistochemically, using antibodies against vascular growth factors (GFs), the receptors of transforming growth factor-beta (TbetaRs) and inducible nitric oxid synthesis (iNOS) in a KD patient without CAL, and also in four control patients: two with CAL due to KD and two without a history of KD. RESULTS: Vascular endothelial GFs, Platelet-derived growth factor-A (PDGF-A) and TbetaRs were expressed in the vascular smooth muscle cells of all patients. PDGF-A, transforming Gfbeta1 and iNOS were expressed in the intimal smooth muscle cells of the KD but not the normal coronary artery without a history of KD. The number of TbetaR-II-positive cells were fewer than TbetaR-I-positive cells in the intima of CAL due to KD, but the number was of both almost same in the intima of coronary artery without CAL after KD and in the normal coronary. CONCLUSION: The intact coronary artery 13 months after KD still showed the influence of the inflammation of KD. Although the authors speculate that the intimal proliferation will not continue beyond the acute phase, those patients may have a risk factor for atherosclerosis.