Noboru Tanaka

Kawasaki Disease With Particular Emphasis on Arterial Lesions

Kawasaki disease (KD, or acute febrile mucocutaneous lymph node syndrome (MCLS)) was first described as a clinical entity in 1967 by Dr. Tomisaku Kawasaki of the Japan Red Cross Medical Center. Originally, it was thought to have a favorable prognosis, but as epidemiological surveys, augmented by pathological studies, have shown, it has come to be recognized as an often fatal disorder. In this report, the clinical symptoms, historical background, present status of research and epidemiological problems of KD are first described, and then we present a pathological and morphological outline of KD, focusing on pathological changes in the blood vessels, and the relationships of these changes to 1) the morphogenesis of arteritis, 2) the mechanism of coronary artery aneurysm formation and its sequelae, and 3) juvenile arteriosclerosis.

PATHOLOGICAL STUDY OF SEQUELAE OF KAWASAKI DISEASE (MCLS): With Special Reference to the Heart and Coronary Arterial Lesions

Unexpected sudden cardiac death among children with a history of Kawasaki disease has come to be reported in Japan. Death occurred between 2 months and 8 years after complete recovery from Kawasaki disease according to our study material. To study the lesions of Kawasaki disease sequelae we examined 61 cases of Kawasaki disease which came to autopsy. In 17 of these the deaths apparently to be due to sequelae of this disease, were characterized by cardiac insufficiency caused by ancient coronary aneurysm with or?anized thrombotic occlusion and superimposed acute ischemic myocardial de?eneration and/or necrosis. The age of the lesions appears to correlate with the interval period between complete recovery from this disease and death. Six cases succumbed incidentally of other causes: one traffic accident, one hemophilus meningitis, one chronic myeloid leukemia, one neuroblastoma, one menin?eal hemorrha?e due to rupture of basilar arterial aneurysm, and one acute lymphatic leukemia. Even in these cases, definite sequelae of arteritis were detected. A surgically resected coronary aneurysm and a ventricular aneurysm were also examined. It was disclosed by mass physical check‐up of school children that 0.1% had a history of Kawasaki disease, among which 5‐6% showed cardiac and/or coronary abnormality includin? aneurysms. The high incidence of cardiac involvement in Kawasaki disease has been proved in this study and this kind of lesion has the possibility of resulting in unexpected cardiac death of children. ACTA PATHOL. JPN. 36: 1513‐1527, 1986.

Coronary artery outcomes among children with Kawasaki disease in the United States and Japan.

OBJECTIVE It has been claimed that the aneurysm rate for Kawasaki disease (KD) patients in Japan is lower than in the U.S. However it has been difficult to compare coronary artery (CA) outcomes between the two countries because of different definitions for CA abnormalities. Therefore, we compared CA internal diameters between Japanese and U.S. KD patients using standard definitions and methods. STUDY DESIGN We retrospectively reviewed CA outcomes in 1082 KD patients from 2 centers in the U.S. and 3 centers in Japan and compared Z-max scores (maximum internal diameter for the left anterior descending or right coronary artery expressed as standard deviation units from the mean (Z-score) normalized for body surface area) obtained within 12 weeks after onset and calculated using two different regression equations from Canada (Dallaire) and Japan (Fuse). We defined a Z-max of < 2.5 as normal and a Z-max of ≥ 10 as giant aneurysm. RESULT The median Z-max for the U.S. and Japanese subjects was 1.9 and 2.3 SD units, respectively (p < 0.001). There was no significant difference in rates of patients with Z-max ≥ 5.0 between the countries. In a multivariable model adjusting for age, sex, and treatment response, being Japanese was still associated with a higher Z-max score. CONCLUSION Previously reported differences in aneurysm rates between Japan and the U.S. likely resulted from use of different definitions and nomenclature. Adoption of Z-scores as a standard for reporting CA internal diameters will allow meaningful comparisons among different countries and will facilitate international, collaborative clinical trials.

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

Analysis of arterial function in adults with a history of Kawasaki disease

BACKGROUND AND PURPOSE It remains controversial whether Kawasaki disease (KD) is a risk factor for the early onset of atherosclerosis. The purpose of the present study was to assess endothelial function and arterial stiffness as markers of the early onset of atherosclerosis in adult patients with a history of KD. METHODS AND SUBJECTS We compared 14 adult patients with a history of KD with 41 healthy controls. To assess arterial endothelial function, we measured the reactive hyperemia-peripheral arterial tonometry (RH-PAT) index and augmentation index adjusted to 75 bpm (AIx@75) using the Endo-PAT 2000 (Itamar Medical, Caesarea, Israel). In addition, we analyzed medical history, blood pressure, lifestyle habits, and atherosclerosis-related serum biochemical markers [asymmetric dimethylarginine, adiponectin, lipoprotein (a), cholesterols, atherogenic index of plasma]. RESULTS There was no difference between the KD and control groups with regard to the RH-PAT index values (2.10 ± 0.43 and 1.84 ± 0.49, respectively; p=0.19). However, in the KD group, the RH-PAT index values were negatively correlated with the febrile period in the acute phase of disease (r(2)=0.458, p=0.048). In addition, the AIx@75 values were higher in KD patients compared to healthy controls (-7.69 ± 11.86% and -15.87 ± 8.72%, respectively; p=0.01). No significant differences existed between the KD and control groups with regard to the serum biomarkers of atherosclerosis. CONCLUSIONS We speculate that endothelial dysfunction in former KD patients is affected by the febrile period of the acute phase, and antiplatelet drugs may improve endothelial function. The increased arterial stiffness of patients caused by post-inflammatory fibrotic changes in the arterial wall indicates that adults with a history of KD have an increased risk of developing atherosclerosis.

A family having type 2B von Willebrand disease with a novel VWF p.R1308S mutation: Detection of characteristic platelet aggregates on peripheral blood smears as the key aspect of diagnosis

Type 2B von Willebrand disease (VWD) is frequently associated with distinct platelet morphology. Here we present a familial case of type 2B VWD with a novel VWF mutation (p.R1308S), which caused neonatal thrombocytopenia. The mother had been treated for refractory immune thrombocytopenia (ITP) for more than 20years. The most important hematological features of this case were large platelets and platelet aggregates detected on peripheral blood smears. Hemostatic tests showed enhanced ristocetin-induced platelet agglutination at low-ristocetin concentrations, absence of high-molecular weight von Willebrand factor (VWF) multimers, and low VWF cofactor activity/antigen ratio. In patients with intractable ITP, family history of ITP and consecutive neonatal thrombocytopenia, the differential diagnosis of congenital thrombocytopenia is mandatory. For this purpose, the identification of large platelets and platelet aggregates on peripheral blood smears is the key aspect of type 2B VWD diagnosis.

Cytological studies of cell sampling methods on automated prescreening for cancer of the uterine cervix - A comparative study on the cervical scraping smears with cotton ball and sponge.

子宮がん細胞診スクリーニング自動化装置CYBEST6-12) の試験的実験応用について, 千葉県対がん協会において, 精密検査被検者を対象として, 細胞診のroutineで使われている綿球と, CYBESTのために考案されたスポンジを用いた細胞採取法との比較, およびその統計的解析を行い, 下記成績が得られた.1) 自動スクリーニング装置CYBESTには, スポンジ採取の方が, 不適合標本が少ない.2) 組織診にてdysplasia, CISと判定された例に対して, 綿球採取による標本はスポンジ採取のそれに比較して, 低異型に判定される傾向があった.3) 異型細胞含有率は, スポンジ採取によるものの方が, 綿球採取のそれに比較して, 高くなる傾向がある.以上の成績から, 細胞採取法として, 綿球に比較して, スポンジ使用の方が, より信頼性が高いと考えられ, CYBESTに用いてきたこの採取法が適切であったことが確認できた

Cytodiagnosis of the Mammary and Extramammary Paget's Diseases

In the present paper, the cytodiagnostic findings of 9patients, having 7 mammary and 2 extramammary Pagetdiseases each, are discussed with emphasis on their cytologic features and mechanism of melanin pigmentationinto the cytoplasma of cancer cells. In the smear specimens collected by scraping or needle-aspiration, largecancer cell clusters occasionally mixed with benign epidermal cells, anisonucleosis, large typical Pagets cells withwide cytoplasma, melanin-pigmentation into the cytoplasma and occasionally presence of melanocytes werecharacteristic for the cytodiagnostic features of the presentdiseases.It is proposed that melanin pigmentation into the cytoplasma of the cancer cells is presumably induced through thesame mechanism as that of epidermal cells reported.