Masami Imakita

Cardiac biopsy in Kawasaki disease

Two hundred one patients (138 boys, 63 girls), 1 month to 11 years old, with Kawasaki disease underwent coronary angiography, ultrasonic tomography, myocardial imaging, and biopsy of right ventricular myocardium. Aneurysms of epicardial coronary arteries, mostly left, occurred in 26 cases (12.9%). Degeneration and proliferation of endothelium, edema, scarring, and fibrosis, slight to moderate, involved the tunicae of intramural small vessels in all cases. These changes tended to abate with time. The basic lesion of Kawasaki disease, round-cell myocarditis and fibrosis, involved all cases and persisted. Disarrangement, abnormal branching, disarray, and hypertrophy of myocytes correlated significantly with myocarditis, but not with epimural or intramural coronary angitis. As a consequence of the myocardial changes, it is suggested that some cases may terminate as myocardiopathy. Scoring criteria for vascular and myocardial changes in biopsy specimens are included.

Second nation-wide study of atherosclerosis in infants, children and young adults in Japan

Abstract This paper reports the results of a nation-wide cooperative study of atherosclerosis in young, first generation Japanese with ages ranging from 1 month to 39 years, who were autopsied between 1978 and 1982 in hospitals distributed over the entire archipelago of Japan. Atherosclerotic lesions in 2320 aortas, 1620 coronary arteries and 344 cerebral arteries were classified into fatty streaks, fibrous plaques and complicated lesions and were then quantificated with the point-counting method. Atherosclerosis of aortas, coronary arteries and cerebral arteries, determined by surface involvement (SI) of atherosclerotic lesions and atherosclerotic index (AI), increased with age; the severest were seen in aortas, and then, with decreasing severity, in the coronary and cerebral arteries. Fatty streaks preceded the other lesions and accounted for the largest portion of the lesions in aortas and coronary arteries. Fibrous plaques and complicated lesions developed in the later decades of life. The patients with collagen diseases had a greater severity of aortic atherosclerosis in the 2nd and 3rd decades of life, than those without such disorders. Correlation of antemortem clinical data with SI and Al of each artery were analyzed, using simple correlation analysis and multiple regression analysis. Age, serum cholesterol and blood pressure were significantly and positively correlated with SI and AI of aortas and coronary arteries. Serum cholesterol was more strongly correlated with the extent of fatty streaks than was mean blood pressure and vice versa with that of fibrous plaques. Atherosclerosis of cerebral arteries, however, showed a significant correlation only with the factor of mean blood pressure. Therefore the susceptibility to risk factors varies with the artery in cases of early lesions of atherosclerosis in young Japanese.

Prophylactic treatment of cytomegalovirus infection with traditional herbs

Hot water extracts of four traditional herbs, Geum japonicum, Syzygium aromaticum, Terminalia chebula and Rhus javanica, which have been shown to have anti-herpes simplex virus (HSV) activity in vivo, were examined for anti-cytomegalovirus (CMV) activity in vitro and in vivo in this study. They inhibited replication of human CMV and murine CMV (MCMV) in vitro. These anti-CMV activities in vivo were examined in an MCMV infection model using immunosuppressed mice. Mice were subcutaneously treated with various doses of cyclosporine, and immunosuppression and MCMV infection were monitored by suppression of antibody production and virus yield in the lung, respectively. Each herbal extract was orally administered to mice treated with 50 mg/kg of cyclosporine from a day before intraperitoneal infection, and the efficacy of herbs was evaluated by the reduction in the virus yield in the lung. Among them Geum japonicum, Syzygium aromaticum, and Terminalia chebula significantly suppressed MCMV yields in lungs of treated mice compared with water treatment. Efficacy of oral treatment with 750 mg/kg per day of Geum japonicum extract was similar to that of the intraperitoneal administration of 2 mg/kg per day of ganciclovir in increasing the body weight of infected mice and reducing the virus yield in the lungs. These herbs may be beneficial for the prophylaxis of CMV diseases in immunocompromised patients.

Late death after arterial switch operation for transposition of the great arteries

Fifty-nine patients survived for more than 1 month after an arterial switch operation (ASO). Diagnoses in these patients included transposition of the great arteries in 27, transposition of the great arteries with ventricular septal defect in 28, and double-outlet right ventricle in four. There were six late deaths (10%) during the follow-up period, and all of them occurred suddenly and unexpectedly. Four of the six late deaths were in patients who had undergone ASO in the neonatal period. Late deaths occurred from 40 days to 10 months after the operation. Autopsies were performed in all six patients. The cause of these late deaths was acute myocardial infarction. Five patients died of subendocardial infarction resulting from stenosis of the left main coronary artery. On pathologic examination, a fibrocellular intimal thickening was noted at the proximal region of the right and left coronary arteries, which resulted in 80% stenosis on average.

Cascade of fever production in mice infected with influenza virus.

The cascade of fever production in influenza was studied. To analyse fever production in a murine model, we selected DBA/2 mice that have the highest susceptibility in fibrile responses among seven mouse strains. Intranasal influenza infection‐ and interferon (IFN)‐induced fever production was studied in this mouse model. Fever was induced prominently on day 2 after influenza infection and IFN activity was also increased in serum. Only the level of interleukin (IL)‐1α, an endogenous pyrogen, rose markedly in serum among cytokines (IL‐1α, IL‐2, IFN‐γ, and tumor necrosis factor‐α) examined. Fever was induced 14 hr after intraperitoneal IFN‐α treatment and IL‐1α level rose significantly in the serum of the IFN‐α‐treated mice as compared with that of untreated mice. Fever production was significantly suppressed by treatment with anti‐IFN‐α/β or anti‐IL‐1α antibody in infected mice and the former signficantly suppressed responsive IL‐1α production, indicating that elevated IFN activity induced IL‐1α production and subsequently fever production in infected mice. The activity of cyclooxygenase (COX) that produces prostaglandin (PG)E2 was significantly augmented in the brain of infected mice on day 2 after infection. Fever production was suppressed by the inhibition of COX activity with aspirin, although IL‐1α level was maintained at the elevated level. Therefore, influenza infection in mice turned on the following cascade for fever induction: IFN production, IL‐1α production, elevated COX activity, and PGE2 production. We elucidated the relationship among IFN activity, IL‐1α production and COX activity and demonstrated the cascade of fever production in influenza infection.

Three autopsy cases of progression to left ventricular dilatation in patients with hypertrophic cardiomyopathy

The hearts of three cases of congestive heart failure with dilated left ventricles developing in patients with symptomatic hypertrophic cardiomyopathy (HCM) were morphologically investigated. The results showed that disproportionate hypertrophy and dilatation of the left ventricles, accompanied by massive fibrosis and myocardial disarray, were present in the three patients. The mean percent area of fibrosis of the left ventricle was 34.7% and 47.4% at the upper third and lower third levels, respectively, and was much more frequently associated with disarray (84.4 +/- 12.3%). Moreover, the fibrosis was most extensive in the lateral wall of the left ventricle, followed by the posterior, anterior, and interventricular walls. The fibrosis was also diffuse regardless of the subendocardial or subepicardial region of the heart. The findings in the present study suggest that the disarray in this particular series of HCM might be responsible for the mechanism of the fibrosis leading to dilatation of the left ventricle.

Congenital nemaline myopathy with dilated cardiomyopathy: an autopsy study.

A 3-year-old boy with congenital nemaline myopathy had generalized muscle weakness and hypotonia since birth. He developed cardiac symptoms at 2 years of age and died from congestive heart failure. At autopsy, the heart was markedly dilated, involving both ventricles. Rod bodies were recognized not only in skeletal muscles but in cardiac muscles on light and electron microscopy. Desmin and alpha-actinin, which constitute Z-line protein, were shown to localize in the rod structures in both skeletal and myocardial cells by immunohistochemistry. Seven cases of nemaline myopathy with cardiomyopathy have been reported in the literature. All of these patients were over 20 years of age, and the condition appeared mostly in the adult onset and the asymptomatic forms. This is the first infantile case of congenital nemaline myopathy which showed dilated cardiomyopathy with a fatal outcome.

Pneumonia Caused by Rhinovirus

Rhinovirus infections, although usually limited to the upper respiratory tract, can extend beyond the oropharynx and may cause complications in the lower respiratory tract, including pneumonia [1‐3]. We describe a case of rhinovirus pneumonia in an infant boy in which rhinovirus was recovered from the lung and analysis of hyperimmune serum to the causal rhinovirus revealed localization of rhinovirus antigen in the lung. At 16 and 22 days of age, an infant boy underwent operations for cardiovascular anomalies, including an interrupted aortic arch and a ventricular septal defect. After the operations, he developed transfusion-associated graft-versus-host disease and died of multiple organ failure at the age of 59 days. At autopsy, the histopathologic findings for the hematopoietic system and the skin were consistent with transfusionassociated graft-versus-host disease. Examination of the lungs showed mild hyperplasia of the bronchial epithelium with cytological alterations, thickening of the alveolar septum, marked hyperplasia of the alveolar lining cells, and desquamating swollen alveolar epithelial cells and macrophages in the alveoli; how

Nodular regenerative hyperplasia of the liver associated with primary pulmonary hypertension

Nodular regenerative hyperplasia (NRH), a rare hyperplastic condition of the liver, is reported in two patients with primary pulmonary hypertension (PPH). The first patient was a 26-year-old man who died of PPH and showed multiple NRH without cirrhosis of the liver. The second patient was a 25-year-old man who had a PPH with pulmonary arterial thrombi and NRH of the liver. NRH has been described in association with immune disease, hematopoietic disorder, and diabetes mellitus, so that NRH with PPH is considered to be very rare. Histologic findings of the lungs show typically plexogenic pulmonary arteriopathy in both cases, and the livers of these patients are composed of multiple nodules that are histologically represented by slightly larger hepatocytes arranged in a cobblestone-like fashion, and are ultramicroscopically characterized by massive proliferation of mitochondria. The pathogenetic association of nodular regenerative hyperplasia with primary pulmonary hypertension will be discussed.

Persistent infection with human polyomavirus revealed by urinary cytology in a patient with heart transplantation. A case report.

BACKGROUND Management after heart transplantation must deal with the twin risks of rejection and infection. Early infection with viral infection, particularly cytomegalovirus (CMV), is becoming more prevalent two to three months after transplantation. To our knowledge, there has been no previous report of human polyomavirus (HPOV) infection after heart transplantation. CASE A 20-year-old male with a history of Kawasaki disease and who had suffered from severe congestive heart failure after a coronary artery bypass graft, underwent heart transplantation. Urinary cytology demonstrated HPOV infection, the diagnosis of which was established by the immunoperoxidase technique, in situ hybridization and electron microscopy. CONCLUSION The definitive diagnosis of HPOV infection after a heart transplant can be made on urinary cytology.