Masahiko Kishiro

Effects of steroid pulse therapy on immunoglobulin-resistant Kawasaki disease

Background: The use of intravenous immunoglobulin (IVIG) is well established as an initial therapy for Kawasaki disease (KD), but treatment for IVIG-resistant KD remains uncertain Aim: To analyse the effects of intravenous methylprednisolone (IVMP) pulse therapy compared with additional IVIG in IVIG-resistant patients. Methods: IVMP was administered to patients with KD who had persistent or recurrent fever after a single dose of IVIG, at Juntendo University Hospital and affiliated medical institutions between May 2003 and March 2006. The effectiveness of the treatment and the incidence of coronary lesions in patients who received IVMP and those who received additional IVIG were retrospectively analysed and compared by chart review. Results: 411 patients with KD were treated with a single dose of IVIG. Of the 63 IVIG-resistant patients, 44 were then given IVMP and 19 were given additional IVIG. Treatment was successful in 34 (77%) of the patients who received IVMP and 12 (63%) who received additional IVIG. Five of the 10 patients who did not respond to IVMP and two of the seven who did not respond to additional IVIG developed coronary artery aneurysms. Although fever initially resolved faster in the IVMP-resistant group, there was a delay in fever recurrence, which ultimately delayed the final resolution of fever. Conclusions: The findings suggest that IVMP is an effective additional treatment for IVIG-resistant KD. However, there was a tendency for fever to recur later in IVMP-resistant patients, which could potentially delay the therapeutic decision-making process.

Age Dependency of Stiffness of the Abdominal Aorta and the Mechanical Properties of the Aorta in Kawasaki Disease in Children

Abstract. Measuring aortic distensibility has been shown to be useful in adults as a noninvasive method in the early detection of atherosclerosis. This study had two purposes: to assess the stiffness of the abdominal aorta by using two-dimensional echocardiography (2DE) in healthy neonates, children, and adults and to assess aortic distensibility in children with Kawasaki disease in acute and subacute phases. The study comprised 168 healthy subjects and 40 patients with Kawasaki disease. We recorded systolic (Ps) and diastolic (Pd) blood pressure and measured aortic diameter (Dd) at both minimum diastolic pressure and maximum systolic expansion (Ds) by 2DE. These measurements were used to determine (1) aortic strain (S) = (Ds−Dd)/Dd, (2) pressure strain elastic modulus (Ep) = (Ps−Pd)/S, and (3) normalized Ep (Ep*) =Ep/Pd. Significant correlations were found between S and age, Ep and age, and Ep* and age. In Kawasaki disease, Ep and Ep* showed negative correlations to day after onset. The aorta was less distensible in infants, became soft in 12- to 16-year-olds, and then stiffened with increasing age among normal subjects. In Kawasaki disease, aortic stiffness was high at the acute phase and normal at the subacute phase. These tendencies may be related to the biological characteristics of smooth muscle cells.

Dilatation Mechanism of Balloon Angioplasty in Children: Assessment by Angiography and Intravascular Ultrasound

AbstractPurpose: Little information is available about the dilatation mechanism in children. This prospective study aimed to (1) evaluate the dilatation mechanism of balloon angioplasty in children with arterial stenosis, and (2) compare the morphological changes seen by intravascular ultrasound (IVUS) and angiography. Methods: Twenty consecutive patients, who had undergone a total of 23 procedures, were examined before and immediately after balloon angioplasty with a 4.3 Fr, 30 MHz rotational tip IVUS system. The lesions for IVUS study had resulted from coarctation of the aorta in six patients, pulmonary arterial stenosis in five, Blalock-Taussig shunt stenosis in three, subclavian artery stenosis in two, renal artery stenosis in two, coronary artery stenosis in one and ductus arteriosus in one. Results: Four distinctive morphological types were identified: type I with arterial stretching, type IIa with superficial tearing, type IIb with deep intimal-medial tearing, type III with flap formation, and type IV with dissection. The diameter of the narrowest site before and after balloon angioplasty increased significantly from 2.1 ± 1.4 mm to 4.6 ± 3.4 mm (p < 0.001). Eighteen of the 23 angioplasty procedures (78%) were considered to be successful, with a dilatation ratio of more than 50%. In most patients with successful dilatation, non-stretch mechanisms such as tearing, flap formation, or dissection were found. The positive percent (70%) of non-stretch mechanisms seen by IVUS was significantly higher than the positive findings (39%) by angiography (Χ2= 6.47, p < 0.02). Conclusions: Non-stretch morphology of the arterial wall may be a common mechanism of dilatation after balloon angioplasty in children with arterial stenosis. IVUS is a useful modality for evaluating the effectiveness of balloon angioplasty and the mechanism of dilatation in individual cases.

Fecal α1-antitrypsin Concentrations as a Measure of Enteric Protein Loss After Modified Fontan Operations

Background Little is known about the enteric protein loss in patients after a modified Fontan operation before the appearance of overt symptoms or signs of protein-losing enteropathy (PLE). The authors examined the possibility of using fecal &agr;1-antitrypsin concentration measurements for the early detection of postoperative PLE and in longer term postoperative monitoring of these patients. Methods The authors compared fecal &agr;1-antitrypsin concentrations in stool samples from 12 children 12.0 to 43.7 months after modified Fontan operations with those of 12 age-matched control subjects and examined the relationship between the &agr;1-antitrypsin levels and time since operation. The authors also compared fecal &agr;1-antitrypsin concentrations of stools from the same patients obtained at two different time points after surgery with intervals between samples ranging from 14.7 to 19.8 months. Results No significant differences in serum total protein and albumin levels were observed between patients after the modified Fontan operation and control subjects. The fecal concentrations of &agr;1-antitrypsin in patients after the Fontan operation were significantly (P < 0.01) higher than those in control subjects. There was no significant correlation between fecal &agr;1-antitrypsin concentrations and time elapsed after the Fontan operation. The fecal &agr;1-antitrypsin concentration increased significantly (P < 0.01) over periods of 14.7 to 19.8 months after the first measurement. Conclusion The results show that enteric protein loss begins before the appearance of hypoproteinemia in patients after a modified Fontan operation, and that the measurement of fecal &agr;1-antitrypsin concentrations in random stool samples is useful as an early indicator. To watch for the development of PLE after Fontan operation, it may be important to perform longitudinal follow-up examinations of enteric protein loss by measuring fecal &agr;1-antitrypsin concentrations early in the postoperative period.

Histopathological characteristics of myocarditis in acute-phase Kawasaki disease

Harada M, Yokouchi Y, Oharaseki T, Matsui K, Tobayama H, Tanaka N, Akimoto K, Takahashi K, Kishiro M, Shimizu T & Takahashi K 
(2012) Histopathology
Histopathological characteristics of myocarditis in acute‐phase Kawasaki disease

Late persistent expressions of ICAM-1 and VCAM-1 on myocardial tissue in children with lymphocytic myocarditis.

BACKGROUND Both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been implicated in cardiac allograft rejection. However, there is little information about the relationship between the expression of these adhesion molecules and myocarditis in children. METHODS AND RESULTS Immunoreactivities of ICAM-1 and VCAM-1 were examined by enzyme immunoassay in 31 biopsy specimens obtained from 11 pediatric patients with biopsy-proven myocarditis or cardiomyopathy. Five of the 11 patients had clear evidence of acute myocarditis. The other 6 had ECG abnormalities identified by mass screening for heart disease, and subsequently had been histologically diagnosed as having non-specific cardiomyopathy. The period between onset of myocarditis or identification of ECG abnormality and immunohistochemical studies was 23 to 60 days and 8 months to 3 years, respectively. Expression of ICAM-1 and VCAM-1 was assessed by counting ICAM-1 and VCAM-1 positive vessels and dividing by the total number of vessels. ICAM-1 was significantly present on 81% (P < 0.01) of myocardial tissue samples in the 5 patients with healing-stage acute myocarditis, and on 45% (P < 0.05) in the remaining 6 patients with non-specific cardiomyopathy, compared with 24% in control specimens obtained from right ventricular muscle resected at surgery for tetralogy of Fallot. VCAM-1 was also present on 50% (P < 0.05) of the samples from the 5 patients with acute myocarditis, but was not present in those with non-specific cardiomyopathy. CONCLUSION This persistent expression of ICAM-1 suggests that myocardial cell damage may persist immunologically for a long period in myocarditis. In addition, immunostaining for these adhesion molecules may be diagnostic value in clinically silent lymphocytic myocarditis and chronic cardiomyopathy.

Histological findings after angioplasty using conventional balloon, radiofrequency thermal balloon, and stent for experimental aortic coarctation

Abstract Background : Use of balloon angioplasty or stent implantation has been reported to be effective in relieving coarctation of the aorta. However, restenosis frequently occurs after balloon angioplasty for native aortic coarctation in small infants, and sometimes develops after stent implantation because of vessel growth. The causes of restenosis remain uncertain. The purpose of this study was to assess the histologic differences in vascular responses to angioplasty using conventional balloon, radiofrequency thermal balloon (RFTB), or stent for experimental aortic coarctation.

Left ventricular torsion and strain in patients with repaired tetralogy of Fallot assessed by speckle tracking imaging.

Background: In patients with tetralogy of Fallot (TOF), left ventricular (LV) dysfunction is an important factor associated with poor clinical outcome. Objective: The purpose of this study was to investigate the torsion and multidirectional strain of the LV in patients with TOF. Methods: Echocardiographic images were prospectively acquired in 29 patients who underwent TOF repair (age range, 5–25 years) and in 29 normal controls. Torsion and circumferential and longitudinal strain of the LV were assessed using speckle tracking imaging. Results: The torsion in patients was smaller compared to that in the controls due to small apical rotation and/or inverse basal rotation (P < 0.01). Torsion and untwisting rates decreased with increasing age (R = 0.37, P < 0.05). Basal circumferential strain and strain rate (SR) at systole and diastole decreased with age (R = 0.58; R = 0.57; R = 0.57, all P < 0.001) and were smaller in patients compared to those in the controls (all P < 0.01). Septal longitudinal strain and SR at systole and diastole decreased with age (R = 0.52; R = 0.62; R = 0.71, all P < 0.001) and were smaller than those of the controls (P < 0.01), although lateral longitudinal strain and SR were relatively maintained. Conclusion: Abnormal torsion and strain pattern of the LV were observed in patients without symptoms of cardiac failure. Assessment of torsion and strain is a very sensitive tool to detect the early deterioration of LV function in patients with TOF. (Echocardiography 2011;28:720‐729)

Enhanced production of interferon-gamma as a possible cause of protein-losing enteropathy after modified Fontan operation.

Protein-losing enteropathy (PLE) is a serious complication after modified Fontan operations in patients with congenital heart diseases (1–5). High central venous pressure with consequent intestinal lymphangiectasia has been suggested as the principal cause of PLE, but other potential contributing factors, such as inflammatory processes, have also been considered (1,4,5). Corticosteroid treatment for patients with PLE after a Fontan procedure has been reported as an effective therapy (1,4,5). Although the precise mechanism of action of corticosteroids is unclear, their effectiveness suggests that autoimmune and inflammatory processes may be one of the pathogenic factors of PLE. The local immune and inflammatory responses have not been fully investigated after Fontan procedure, and, to our knowledge, there has been no study of cytokine levels or electron microscopic findings in the small intestinal mucosa of patients with PLE after a Fontan operation. We report a boy who developed PLE after a modified Fontan operation. A jejunal biopsy was performed in this child before and after successful corticosteroid treatment of his PLE. Histologic analysis and measurement of the cytokine levels in the small intestinal mucosa were performed.

Non-invasive assessment of liver fibrosis in patients after the Fontan operation

Background:  This study analyzed the change in liver fibrosis markers after the Fontan operation and investigated their clinical usefulness as an index of congestive liver fibrosis.