Kawasaki Disease Lesions Research Articles

Intravenous immunoglobulin does not increase Fc RIIB expression on monocytes/macrophages during acute Kawasaki disease

Intravenous immunoglobulin (IVIG) therapy has been reported to be effective for reducing the incidence of coronary artery lesions in Kawasaki disease (KD), an acute febrile vasculitis of unknown aetiology. Regarding the mechanism of IVIG in immune thrombocytopenic purpura (ITP), it has been reported that IVIG increases the expression of the inhibitory Fc receptor, FcgammaRIIB (CD32B), on splenic macrophages in a murine ITP model. Regarding the mechanism of IVIG during acute KD, we investigated whether or not IVIG increases the expression of FcgammaRIIB in peripheral blood CD14+ monocytes/macrophages. The expression of FcgammaRIIB in peripheral blood CD14+ monocytes/macrophages was determined before and after IVIG therapy in 13 patients with acute KD by flow cytometry. The percentage of CD14+ CD32B+ monocytes/macrophages among peripheral blood mononuclear cells, the absolute number of CD14+ CD32B+ monocytes/macrophages and the percentage of CD14+ CD32B+ monocytes/macrophages among CD14+ monocytes/macrophages in patients with acute KD before IVIG therapy were significantly increased compared with those after IVIG therapy and in controls. CD14+ CD32B+ monocytes/macrophages decreased to within the normal range soon after IVIG therapy. IVIG therapy in patients with KD did not increase the expression of FcgammaRIIB in peripheral blood CD14+ monocytes/macrophages during the acute stage.

Polymorphism of Matrix Metalloproteinase-3 Promoter Gene as a Risk Factor for Coronary Artery Lesions in Kawasaki Disease

Kawasaki disease (KD) is a major cause of acquired coronary artery diseases in childhood. The serum levels of matrix metalloproteinase (MMP)-3 and MMP-9 in KD have been reported to be significantly higher than other diseases. Several studies have demonstrated that MMP-3 5A/6A polymorphism and MMP-9 C-1562T polymorphism modify each transcriptional activity in allele specific manner. We hypothesized that these polymorphisms may play a role as a risk factor for development of coronary artery lesions (CAL) in KD. Eighty-three patients, diagnosed with KD in Cheju National University Hospital from January 2000 to February 2004, were divided into two groups according to the presence of CAL. Genotyping of MMP-3 and MMP-9 gene polymorphisms were determined by restriction fragment length polymorphism. With regard to MMP-3 gene polymorphism, the KD with CAL group had a higher frequency of 6A/6A genotype than control group (p=0.0127) and the KD without CAL group (p=0.0036). However, no significant differences in the allele and genotype distributions of the MMP-9 polymorphism were observed. These findings suggest that MMP-3 6A/6A genotype may be an independent risk factor for CAL formation in KD.

Polymorphisms in the mannose-binding lectin gene as determinants of age-defined risk of coronary artery lesions in Kawasaki disease

To evaluate the relationship between polymorphisms in the gene coding for mannose-binding lectin (MBL) and the occurrence of coronary artery lesions (CALs) among different age groups of patients with Kawasaki disease. The frequencies of the genotypes, defined as mutations in codons 52, 54, and 57, and the functional promoter variants of the MBL2 gene were determined in 88 patients with acute Kawasaki disease (median age at onset 1.9 years). The possible influence of the MBL2 genotype on the development and progression of CALs in Kawasaki disease was assessed according to age categories and MBL genotypes in univariate and multivariate analyses. In patients younger than age 1 year, we found an increased risk of developing CALs in the presence of a variant MBL2 genotype (P = 0.008). In contrast, in patients older than age 1 year, we found an increased risk of CALs in those patients with the wild-type genotype (P = 0.005). Our findings indicate that MBL has an ambiguous role in Kawasaki disease and contributes differently to the pathophysiologic development of CALs, being protective in infants but potentially harmful in patients of older age. The data also imply that the standard treatment of intravenous immunoglobulins to reduce the development of lesions may not be as effective in the very young as it is in the older patients. For the very young, alternative or adjuvant treatment may be indicated, particularly in infants who are MBL-deficient.

Meta-analysis of the results of intravenous gamma globulin treatment of coronary artery lesions in Kawasaki disease

The objective of this study was to evaluate the efficacy of intravenous gamma globulin (IVGG) therapy on the prevention of coronary artery lesions (CALs) in patients with Kawasaki disease (KD), with reference to the literature on meta-analyses in randomized controlled studies. Studies from 1984 to the end of 2000 obtained from the National Library of Medicine or from the bibliographies of these articles were used in the analysis. The total number of patients with KD covered in 17 articles was 4020. All the articles were examined for the number of doses per day, the duration of administration, and the total number of IVGG doses. The number of patients in each group was counted, and the incidence of CALs was evaluated at 30 or 60 days after onset. The results of these searches were further analyzed by meta-analytical methods. The administration of IVGG significantly decreased the incidence of CALs in a dose-dependent manner: at 30 days after onset the incidence of CALs was 29.4% without IVGG but 21.6% with a total dosage of IVGG < 1000 mg/kg, 10.8% with a total dosage of 1000-2000 mg/kg, and 10.2% with a total dosage of > or =2000 mg/kg. Compared with the incidence of CALs without IVGG, the odds ratio (OR) was 0.662 [95% confidence interval (CI) 0.519-0.815)] at <1000 mg/kg, 0.292 (95% CI 0.222-0.371) with 1000-2000 mg/kg, and 0.274 (95% CI 0.207-0.349) with > or =2000 mg/kg. At 60 days, the values had decreased to 17.3%, 13.8% [OR 0.767 (95% CI 0.585-1.005)], 5.8% [OR 0.296 (95% CI 0.200-0.436)], and 4.9% [OR 0.244 (95% CI 0.170-0.349)], respectively. The meta-analyses also indicated that high doses of IVGG (> or =2000 mg/kg per day) given in a single dose prevented CALs more effectively than the same dosages divided into five daily doses in the patients with KD: The incidence of CALs at 30 days after disease onset was 2.4% with a single dose versus 12.9% with divided doses. Compared with divided doses, the OR with a single dose was 0.164 (95% CI 0.064-0.393) and 2.8% versus 6.1% at 60 days [OR 0.450 (95% CI 0.206-0.956)]. We clearly confirmed that higher doses of IVGG (> or =2000 mg/kg per day) administered in a single infusion were more effective for preventing CALs, as evaluated during both the subacute and convalescent phases of KD.

Meta-analysis of the results of intravenous gamma globulin treatment of coronary artery lesions in Kawasaki disease

The objective of this study was to evaluate the efficacy of intravenous gamma globulin (IVGG) therapy on the prevention of coronary artery lesions (CALs) in patients with Kawasaki disease (KD), with reference to the literature on meta-analyses in randomized controlled studies. Studies from 1984 to the end of 2000 obtained from the National Library of Medicine or from the bibliographies of these articles were used in the analysis. The total number of patients with KD covered in 17 articles was 4020. All the articles were examined for the number of doses per day, the duration of administration, and the total number of IVGG doses. The number of patients in each group was counted, and the incidence of CALs was evaluated at 30 or 60 days after onset. The results of these searches were further analyzed by meta-analytical methods. The administration of IVGG significantly decreased the incidence of CALs in a dose-dependent manner: At 30 days after onset the incidence of CALs was 29.4% without IVGG but 21.6% with a total dosage of IVGG < 1000 mg/kg, 10.8% with a total dosage of 1000–2000 mg/kg, and 10.2% with a total dosage of ≥2000 mg/kg. Compared with the incidence of CALs without IVGG, the odds ratio (OR) was 0.662 [95% confidence interval (CI) 0.519–0.815)] at <1000 mg/kg, 0.292 (95% CI 0.222–0.371) with 1000–2000 mg/kg, and 0.274 (95% CI 0.207–0.349) with ≥2000 mg/kg. At 60 days, the values had decreased to 17.3%, 13.8% [OR 0.767 (95% CI 0.585–1.005)], 5.8% [OR 0.296 (95% CI 0.200–0.436)], and 4.9% [OR 0.244 (95% CI 0.170–0.349)], respectively. The meta-analyses also indicated that high doses of IVGG (≥2000 mg/kg per day) given in a single dose prevented CALs more effectively than the same dosages divided into five daily doses in the patients with KD: The incidence of CALs at 30 days after disease onset was 2.4% with a single dose versus 12.9% with divided doses. Compared with divided doses, the OR with a single dose was 0.164 (95% CI 0.064–0.393) and 2.8% versus 6.1% at 60 days [OR 0.450 (95% CI 0.206–0.956)]. We clearly confirmed that higher doses of IVGG (≥2000 mg/kg per day) administered in a single infusion were more effective for preventing CALs, as evaluated during both the subacute and convalescent phases of KD.

Advances in the imaging of vascular complications and their impact

Remarkable advances in cardiovascular diagnostic imaging now permit greatly improved assessment of coronary arterial lesions in Kawasaki disease. In particular, real-time three-dimensional echocardiography, multi-slice spiral computed tomography, and magnetic resonance coronary angiography now represent useful noninvasive methods to image coronary artery abnormalities. Myocardial perfusion imaging with technetium-99 m as well as positron emission tomography can be used for myocardial blood flow evaluation. In addition, quantitative gated single-photon emission computed tomography is being used for functional cardiac evaluation.

Coronary artery lesions in Kawasaki disease

Coronary artery lesions in Kawasaki disease

Oxygen Radicals Activity as a Predictor of Coronary Artery Lesions in Kawasaki Disease

Background Neutrophil-derived Oxygen radicals (OR) play a role in a wide variety of diseases including vasculitis syndrome, however, little is known about causal relation between coronary artery lesions (CAL) in Kawasaki disease (KD) and OR activity.Objective To investigate a role of OR in CAL. Methods 27 patients with KD were enrolled within 7 days from the onset of illness. All patients were treated orally with aspirin (ASA), and 21 patients, selected by Harada scoring system, also received intravenous gammaglobulin therapy (IVGG). IVGG was administered as daily infusions of 200mg/Kg for five consecutive days. Patients were retrospectively divided into the following three groups according to IVGG and CAL: Severe group, patients with CAL treated with IVGG (n=3); Moderate group, patients without CAL treated with IVGG (n=18); and Mild group, patients without CAL not needed IVGG (n=6). 15 healthy children were studied as controls. Neutrophil-derived OR were measured as intracellular chemilluminescense (ICCL) of whole blood by luminol-dependent chemilluminescense method using luminol-binding microsheres. Serial changes in ICCL values were monitored from acute to convalescent phases in every patient.Results Significant differences were observed in pretreatment ICCL values among the three groups with KD (p<0.05). The mean ICCL values in mild, moderate and severe groups of KD were 13.7±5.5x105cpm, 34.8±9.3x105cpm, and 71.2±10.1x105cpm, respectively, while that in control was 3.1±1.2x105cpm (p<0.01). In IVGG groups, the ICCL values were significantly decreased at 1 and 4 weeks after treatment: 19.2±8.4x105cpm and 8.1±3.3x105cpm in moderate group (p<0.05), and 39.8±7.7x105cpm and 20.3±9.2x105cpm in severe group (p<0.05). Thus, patients with CAL (severe group) had persistently much higher ICCL values than patients without CAL (mild and moderate groups)(p<0.05).Conclusions OR activity was well correlated with severity of KD in acute phase and decreased in parallel with IVGG. OR activety appears to be useful for predicting the risk of CAL despite IVGG, and possibly helping earlier decision on an alternative treatment.

Coronary Arteritis and Arterial Remodeling in Kawasaki Disease: Immunohistochemical Study

This study aimed to develop innovative therapy to prevent obstructive coronary arterial lesions in Kawasaki disease (KD). We studied fundamental mechanisms related to arteritis in acute phase and remodeling of the arteries in convalescent and late phase. We examined formalin-fixed specimens of coronary arteries from 18 patients with KD by immunohistochemical staining. We used antibodies against various vascular growth factors, including TGFβ1, PDGF-A, bFGF, VEGF and their receptors. We also used cell type-specific antibodies to CD68, CD34, factor VIII and α-actin. In acute phase (15th day of illness), severe edema and inflammatory cell infiltration were observed in the arteries, especially in the area from adventitia to intima. In convalescent phase (2.5-12.5 months after onset), we observed synthesis of loose gelatinous extra-cellular matrix (ECM) that leads to intimal thickening and occlusion of aneurysmal lumen. Inflammatory cells, such as iNOS+ cells, VEGF+ cells, and CD68+ macrophages, infiltrated in the ECM of subendothelial layer and deep intima by one year after onset of KD. Among the infiltrating cells, a large number of CD34+ cells, Tie2+ cells and KDR+ cells, known as endothelial progenitor cells (EPCs), were seen to migrate from adventitia to deep intima. In the later convalescent phase, the loose gelatinous ECM was replaced by smooth muscle cells (SMCs) and collagen fibers. In late phase (2.5-19 years after onset), the growth factors were strongly expressed in proliferating SMCs of progressively thickening intima. In conclusion, this study indicated that the remodeling of coronary arteries begins with synthesis of ECM in the intima and cellular infiltration. Thereafter, vascularization, remarkable proliferation of SMCs and fibrosis are occurred in order. In addition, it became obvious the remarkable vascularization in KD depends on not only angiogenesis but also postnatal vasculogenesis that was proved by infiltration of a large number of EPCs.

Serum hepatocyte growth factor combined with vascular endothelial growth factor as a predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease

We investigated the possible use of serum hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) levels as a predictive indicator for the occurrence of coronary artery lesions (CAL) in Kawasaki disease (KD). Serum HGF and VEGF levels were measured by enzyme-linked immunosorbent assay in 41 patients with KD and 25 afebrile controls. Serum HGF levels of patients in the acute phase of KD were significantly higher than those of afebrile controls (Pc < 0.05) and decreased to lower levels during recovery (P < 0.0001). Univariate analysis showed significant correlations between occurrence of CAL and five variables: duration of fever (P=0.018), serum C-reactive protein concentration (P = 0.024), albumin concentration (P=0.009). serum VEGF level (P=0.009) and serum HGF level (P=0.035). Furthermore, multivariate analysis revealed that serum HGF and VEGF levels and presence of oedema were major risk factors for the occurrence of CAL. For prediction of the development of CAL, we established a new risk classification system with these three variables, which showed a sensitivity of 100% and a specificity of 94.4%. these data show that hepatocyte growth factor, together with vascular endothelial growth factor, might play an important role in the pathophysiology of Kawasaki disease and their serum levels could be a powerful predictor for the development of coronary artery lesions.

Active remodeling of the coronary arterial lesions in the late phase of Kawasaki disease: immunohistochemical study.

Remodeling of the coronary artery lesions in Kawasaki disease has been observed in longitudinal angiographic studies. However, mechanisms of such remodeling have not yet been elucidated. We examined formalin-fixed specimens of the coronary arteries immunohistochemically by using antibodies against vascular growth factors (GFs) and their receptors in 7 children with Kawasaki disease, 9 children with no coronary disease, and 3 adults with atherosclerosis. In the thickened intima at stenotic sites and at recanalized vessels with Kawasaki disease, extensive expression of vascular GFs, such as transforming GF-beta(1), platelet-derived GF-A, and basic fibroblast GF, was observed both within and surrounding smooth muscle cells. Vascular endothelial GF was observed within smooth muscle cells. Furthermore, all of these GFs were strongly expressed in the newly formed microvessels within the intima. In the thinned media, these GFs were focally and weakly expressed. In contrast, these GFs were expressed only in the media in the control children. In cases of adult atherosclerosis, GFs were expressed diffusely in the media but focally and weakly if at all in the intima. Active remodeling of the coronary artery lesions in Kawasaki disease continues in the form of luxuriant intimal proliferation and neoangiogenesis for several years after the onset of the disease. This process is distinct from adult-onset atherosclerosis.

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 (rs = 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. Serum vascular endothelial growth factor level, in combination with persistence of fever, could be a powerful predictor for the development of coronary aneurysms.

Tachycardia as a potential risk indicator for coronary arterial lesions in Kawasaki disease.

Tachycardia is frequently observed in the acute phase of Kawasaki Disease (KD) patients. However, little is known about the association between the tachycardia in the acute phase of KD and the development of coronary arterial lesions (CAL). We examined the association between the mean 24 h heart rate in the acute phase of KD observed using 24 h ambulatory ECG monitoring (24 h-ECG) and the occurrence of CAL in patients. In a study conducted between 1994 and 1997, 26 patients with KD underwent 24 h-ECG within the febrile period and before the 9th day of illness. We compared the mean 24 h heart rate based on 24 h-ECG between patients with and those without CAL. Of 26 patients, 7 had CAL. The groups with and without CAL had similar baseline characteristics. The mean 24 h heart rate in the group with CAL was significantly higher than that in the group without CAL (144 +/- 14 vs. 124 +/- 22, P = 0.033). On multiple regression analysis, the mean 24 h heart rate was significantly correlated with the development of CAL (P = 0.019). Marked tachycardia detected by 24 h-ambulatory ECG monitoring in the acute phase of Kawasaki disease might provide important information on the development of coronary arterial lesions.

Natural history of coronary artery lesions in Kawasaki disease

Kawasaki disease is associated with significant caronary arterial damage. The natural history and methods of diagnosis of the various lesions were studied in 433 patients who were evaluated by serial 2-D echocardiographic and coronary arteriographic studies during acute, chronic and long-term phases of the disease. All patients with coronary artery lesions received anticoagulation treatment to prevent thrombosis and stenosis. Aortocoronary bypass surgery was performed in 42 (6.7%) of all patients. Eight patients died from myocardial ischemia. In a subset of patients, studies showed persistent coronary aneurysms at the 30th day of illness in 18% of patients treated with aspirin and in 13% who received intravenous immune gamma globulin. During the acute and subacute phases of KD, thrombosis of an aneurysm was the most dangerous and important complication to recognize because of the need for anticoagulation treatment to prevent ischemic myocardial damage or death. Significant coronary arterial obstruction of one form or another occurred in 128 (29.6%) of the 433 patients during early and late phases of the disease. Complete coronary arterial occlusion occurred in 67 (15.5%) of patients and segmental stenosis developed in 64 (14.8%) of them. Localized stenosis was seen, often years after the disease, in 162 (37.4%) of patients, and imaging studies of myocardial blood flow were most sensitive at identifying ischemia, a silent complication in many of them. Significantly abnormal intimal thickening was demonstrated by intracoronary arterial ultrasound measurements in segments of regressed aneurysms, persistent aneurysms, and apparently normal coronary arteries in studies of 40 patients years after the onset of coronary damage. Thickening in main coronary trunks and at arterial branch sites was common in older patients and was considered as a potential precursor for adult atherosclerosis. A subnormal vasoreactivity to intracoronary nitroglycerin was also found at these sites, indicating the dynamic nature of coronary damage years after Kawasaki disease. The morphology, reactivity to vasodilation, and specific natural history of various types of coronary artery damage from Kawasaki disease has been characterized in this longitudinal study of 433 patients. These experiences have identified useful techniques for the diagnosis and treatment of coronary artery disease occurring over many years.

Coronary arterial and myocardial lesions in Kawasaki disease at convalescent stage

川崎病における冠動脈病変の長期的予後は成人に達した症例が少ないため不明点が多い. 筆者らは本疾患の長期予後の良好例と不良例を発症早期の段階で鑑別予知できるか否かについて, 1) 急性期から反復施行した冠動脈造影の経時的変化, 2) 種々の時期の心筋生検所見, 3) 心エコーの新しい指標である左室壁応力を用いた左心機能評価, の3点から後方視的に検討した. 対象は冠動脈造影を施行した278症例である. 方法は冠動脈造影を後方視的に観察し病変の進展について検討した. うち心筋生検を施行した11例ではその組織所見および遠隔期での心機能評価, また重症冠動脈病変をもった25例では左室壁応力を用いて左心機能を評価した. その結果, (1) 冠動脈造影では急性期の瘤最大径8mm以上の巨大冠動脈瘤が狭窄性病変への進展を認め, 狭窄は右冠動脈では発症から3年以内の早期に, 左冠動脈では5年以上の遠隔期に出現する傾向にあった. また正常径にregressionした後にも狭窄病変へと進展する例を左冠動脈に少なからず認めた. 中等度の拡張でもlong-segmentalな病変に狭窄病変に進展する例があった. (2) 11症例の心筋生検症例では, 全例程度の差はあるが間質の線維化, 軽度の細胞肥大, 錯綜配列を認めた. これらの心筋炎所見は発症から6カ月後も認められ, 更に線維化は発症10年後も明らかに残存していた. しかし生検後平均7年の観察中心エコー・MRIなどの検査で心筋症様所見を呈した症例は認めず, 心機能は正常であった. (3) 壁応力を用いた左心機能評価では心筋梗塞症例および重症狭窄病変合併例以外の殆どの症例で異常所見は認めなかった. 以上より川崎病では冠動脈障害が長期予後を左右する重要な因子であり冠動脈瘤の径が大きい例ほど狭窄性病変へ進展する傾向にあったが, 巨大冠動脈瘤のみならず中等度の冠動脈病変を有する症例の中にも形態によっては予後不良例があり, また瘤の出現部位が左右冠動脈のどちらかによっても予後が異なった. 心筋炎は病理組織では長期経過後も残存するが予後に与える影響は少ない. 急性期に巨大冠動脈瘤が認められた例やlong-segmentalな病変を有する例は成人期に達しても経過観察が必要である.

Functional behavior and morphology of the coronary artery wall in patients with Kawasaki disease assessed by intravascular ultrasound

Objectives. To examine the development of coronary artery lesions in Kawasaki disease, we assessed the functional behavior and morphology of coronary arteries by intravascular ultrasound.Background. Long-term follow-up studies of patients with Kawasaki disease have demonstrated the development of localized coronary stenoses even after aneurysms have regressed. It is also possible that angiographically normal coronary segments in patients with this disease may retain histologic changes.Methods. Twenty-three patients followed up by serial coronary angiography were examined at a mean age ± SD of 14.9 ± 2.9 years. The thickness of the intima-media complex was measured by intravascular ultrasound (30 MHz; 3.5 or 4.3F; 1,800 rpm). Coronary reactivity to nitroglycerin was determined by measuring percent changes in cross-sectional coronary artery area after intracoronary injection (7 μg/kg body weight) of this agent.Results. A remarkably thickened intima-media complex was observed at the sites with persisting (0.54 ± 0.20 mm, n = 19) and regressed (0.84 ± 0.40 mm, n = 23) aneurysms. Mild thickening of the intima-media complex was often observed even in angiographically normal segments (0.22 ± 0.05 mm, n = 31), in the left main coronary artery (0.47 ± 0.15 mm, n = 20) and at normal branches (0.36 ± 0.09 mm, n = 13). Coronary reactivity to nitroglycerin was significantly lower at the sites of regressed aneurysms (12.8 ± 6.6%, n = 9) than in normal segments (32.8 ± 10.9%, n = 13, p < 0.01), indicating the presence of functional impairment at the sites with regressed aneurysms. Decreased nitroglycerin reactivity was also observed in some segments without evidence of aneurysm.Conclusions. These results indicate that in patients with Kawasaki disease the coronary disease accompanying impaired reactivity to nitroglycerin is present at the sites of regressed aneurysms as well as in angiographically normal coronary segments. We suggest that these sites with morphologic and functional abnormalities are related to the development of significant stenosis.

The Induction of Cardioangitis byLactobacillus caseiCell Wall in Mice: I. The Cytokine Production from Murine Macrophages byLactobacillus caseiCell Wall Extract

A single intraperitoneal injection of the water-soluble cell wall extract fromLactobacillus casei(LCWE) in mice can induce acute inflammatory heart involvement such as cardiac arteritis, similar to the heart lesions in Kawasaki disease. To clarify whether inflammatory cytokines participate in pathogenic mechanisms of LCWE-induced cardioangitis in mice, we studiedin vitrocytokine production (IL-1, TNFα, and IL-6) from peritoneal macrophages (Mφ) stimulated with LCWE in comparison with that of lipopolysaccharide (LPS). LCWE significantly activated Mφ of BALB/c in production of IL-1 and TNF α compared with LPS. However, the magnitude of IL-6 synthesis by LCWE was approximately similar to that LPS. These results demonstrate that the pathogenesis of LCWE-induced cardiac lesions may be associated with increased production of inflammatory cytokines.

Angioscopic observation of coronary lesions in Kawasaki disease

Angioscopic observation of coronary lesions in Kawasaki disease

Mononuclear cell subsets and coronary artery lesions in Kawasaki disease.

The peripheral blood mononuclear cell subsets in patients with Kawasaki disease and coronary artery lesions were investigated. Of the 106 patients 14 had lesions. Patients with Kawasaki disease and coronary artery lesions were found to have increased counts of CD14+ macrophages/monocytes compared with those of patients with Kawasaki disease without lesions. The absolute counts of CD14+ macrophages/monocytes form an important parameter to determine the severity of vascular damage during acute Kawasaki disease.

Surgical management for cardiovascular lesions in Kawasaki disease

SummarySummary Myocardial revascularization is now an accepted therapeutic modality for severe coronary arterial obstructive disease produced by Kawasaki disease which is amenable to usual medical treatment. The mortality rate of myocardial infarction is surprisingly high in this setting, and surgery may be able to prevent many of these deaths. This article focuses on current issues in surgical treatment of ischemic heart disease in children secondary to Kawasaki disease. Coronary arterial obstructive disease is, apparently, a leading problem followed by valvar and myocardial involvements. Introduction of bypass grafting using the internal thoracic artery in children was a major recent advance, because this graft has an excellent capability to adapt to the increments of increased flow and growth of the patient. The saphenous vein is less satisfactory when used as a graft in terms of its long-term patency, particularly in young children less than 8 years old. Although longer follow-up is certainly required, the current results of surgery have been excellent in improving myocardial perfusion, in ameliorating symptoms, and improving the quality of life.