Linear shadows inside coronary arterial lesions on two-dimensional echocardiograhpy in Kawasaki disease patients.

BACKGROUND: Conventional two-dimensional echocardiography (2DE) is not adequately sensitive enough for the detection of stenotic or occlusive coronary lesions that occur in Kawasaki disease. Recently, linear shadows have been detected inside large- or moderate-sized coronary artery lesions (CALs) by high-resolution 2DE at a convalescent or chronic stage. PURPOSE AND METHODS: We evaluated the clinical significance of the linear shadows detected by 2DE and compared the findings with those obtained using coronary angiography (CAG), magnetic resonance imaging (MRI), and intravascular ultrasound (IVUS). RESULTS: From December 2001 to November 2006, linear shadows were detected in 11 out of 18 CALs in 9 patients at our institution. The outer diameters of the CALs by 2DE were larger than the diameters of CALs by CAG, while the inner diameters between the linear shadows by 2DE correlate with the diameters of CALs by CAG. Remarkably thickened intima was confirmed in 7 out of 9 CALs by MRI, and in every lesion that was examined using IVUS. CONCLUSIONS: The results of this study suggest that linear shadows by 2DE would indicate the existence of a thickened intima. We consider that linear shadows may be useful to estimate the development of stenotic lesions during the process of regression or remodeling of CALs.

MMP-2 inhibition reduces renal macrophage infiltration with increased fibrosis in UUO.

We examined the role of matrix metalloproteinase-2 (MMP-2) in renal fibrosis and its effect on interstitial macrophage infiltration in a mouse model of unilateral ureteral obstruction (UUO). TISAM, a selective inhibitor of MMP-2, was administered during early stage (day -2 to 4; protocol A) and late stage (day 7 to 13; protocol B) after UUO. Treatment with TISAM accelerated fibrosis both at day 5 (A) and at day 14 (B). The degree of macrophage infiltration was decreased by the treatment with TISAM at day 14, but not at day 5. In vitro macrophage migration assay showed a greater migration to renal tissue of control UUO kidney (day 14) than to TISAM-treated kidney, which was suppressed by preincubating macrophages with RGDS, a fibronectin degradation peptide. These results suggest that MMP-2 acts to accelerate macrophage infiltration in the late stage of UUO, possibly by degrading extracellular matrix components.

A randomized prospective study on the use of 2 g-IVIG or 1 g-IVIG as therapy for Kawasaki disease.

A single, 2 g/kg dose of immune globulin (IG), denoted 2 g-intravenous (IV)IG, has become a standard regimen for treating Kawasaki disease (KD) because of its highly preventive effect on coronary arterial lesions (CAL). However, IG is obtained from blood specimens, a drawback to many patients, and is also very expensive. This randomized prospective study reported here was carried out with the aim of developing a treatment regimen that would reduce the total dose of IG. The study tested two protocols (A: 2 g-IVIG; B: 1 g-IVIG) that included the strategy of administering additional IVIG to IVIG-resistant patients based on the criteria we described previously. In protocol A, an additional 2 g-IVIG was administered only once; in protocol B, the first additional IVIG was 1 g-IVIG and the second was 2 g-IVIG. One hundred and nine patients who were admitted before the seventh day of illness and had no CAL at the time of admission were enrolled in the study (protocol A: 54 patients; B: 55 patients). In the protocol A group, 7.4% (4/54) of the patients received 4 g/kg IG. In protocol B, 41.8% (23/55) were treated only with 1 g/kg IG, and 10.9% (6/55) received 4 g/kg IG. No significant differences were observed between the patients of the two subgroups receiving 4 g/kg IG in each protocol group. Discriminate analysis also suggested that 52.4% of the patients in the protocol A group could be treated only with 1 g/kg IG. On the other hand, no significant difference was observed in the incidence of aneurysms between patients in the protocol A group (1/54) and those in the protocol B group (4/55). Our protocol based on 1 g-IVIG, including additional IVIG, was assessed to be an effective treatment and to provide a considerably useful means to reduce the total dose of IG.