Jing Ming Wu

Pathogenesis of Enterovirus 71 Brainstem Encephalitis in Pediatric Patients: Roles of Cytokines and Cellular Immune Activation in Patients with Pulmonary Edema

Taiwan experienced several epidemics of enterovirus 71 (EV71) infections, which were associated with brainstem encephalitis (BE) and pulmonary edema (PE). To elucidate the role of immune mechanisms in the pathogenesis of BE caused by EV71 and its fatal complication, PE, we analyzed the laboratory findings, cytokine, and immunophenotypes of 73 EV71-infected patients with BE. Patients were stratified by disease: PE (n=14), autonomic nervous system (ANS) dysregulation (n=25), and isolated BE (n=34). The mortality rate for PE was 64.3%. Leukocytosis and thrombocytosis were significantly more frequent among patients with PE. A significant elevation of plasma interleukin (IL)-10, IL-13, and interferon (IFN)-gamma levels observed in patients with PE. Patients with PE also had lower circulating CD4(+) T cells, CD8(+) T cells, and natural killer (NK) cells. An extensive peripheral and central nervous system inflammatory response with abnormal IL-10, IL-13, and IFN-gamma cytokine production and lymphocyte depletion appears to be responsible for the pathogenesis of EV71-associated PE.

Complete atrioventricular block following myocarditis in children.

AbstractComplete atrioventricular block (CAVB) can be either congenital or acquired in children. Acquired CAVB is occasionally seen in myocarditis patients. To determine the etiology, natural history, and outcome of children with acquired nonsurgical CAVB, we retrospectively reviewed nine children who had suffered CAVB caused by suspected infectious myocarditis. All of them had CAVB with a wide QRS escape ventricular rhythm on admission. Three of them had ventricular tachycardia in addition to CAVB. Seven of them had a preceding upper respiratory tract infection. All of them had congestive heart failure. Five of them had Stokes–Adams seizures. Three etiologies were identified in four of the children. All patients received inotropic agents and emergency temporary pacing. In all except one case, the cardiac rhythm returned to sinus rhythm within 10 days. During a follow-up period of 9 to 96 months, all were asymptomatic and drug-free. Electrocardiograms showed that four patients were completely normal, there was complete RBBB in four and left anterior fascicular block in one patient. We conclude that although CAVB associated with myocarditis can be life-threatening, the long-term prognosis is good if patients are diagnosed early and proper management is employed.

Pulmonary Cavernous Hemangiomatosis Treated with Interferon Alfa-2a

Pulmonary hemangiomatosis is a rare, usually fatal disorder characterized by diffuse proliferation of blood vessels within the thorax. We describe a 7-year-old boy with cavernous-type pulmonary hemangiomatosis successfully treated with interferon alfa-2a. He presented with respiratory distress and hemoptysis that were alleviated during a 2-year follow-up period.

Pulsed high-dose dexamethasone therapy in children with chronic idiopathic thrombocytopenic purpura

Purpose The effectiveness of pulsed high-dose oral dexamethasone therapy in children with refractory chronic idiopathic thrombocytopenic purpura (ITP) is evaluated. Patients and Methods Seven children (5 to 16 years old) who were refractory to 2 to 5 conventional standard therapies were included in the study. Dexamethasone was administered orally at a dosage of 40 mg/m2 per day (maximum 40 mg/day) for 4 consecutive days as a cycle. The cycle was repeated once a month for 6 months. Results One month after the first cycle, partial responses of platelet counts (>50±109/L and <150±109/L) were observed in three patients (43%). At the end of the sixth cycle, two patients (29%) had complete responses (>150±109/L) and one had a partial response. However, only one patient (14%) remained partially responsive 1 year after completion of therapy. Conclusions In contrast to what was observed in adults, this preliminary study suggests that pulsed high-dose oral dexamethasone therapy was not uniformly effective in children with chronic ITP.

Critical management in patients with severe enterovirus 71 infection

Objective: The aim of this study was to analyze clinical details occurring in children with severe enterovirus 71 (EV71) infection and synthesize the critical care experience for patients with severe EV71 infection.

Isolated congenital left ventricular diverticulum.

Congenital diverticulum of the left ventricle, a rare malformation, is usually associated with midline thoracoabdominal defect. We describe a case with congenital left ventricular diverticulum presenting as an isolated lesion. The lesion was suspected on two-dimensional echocardiography and was confirmed by cardiac catheterization and magnetic resonance imaging.

Invasion of the cardiovascular system in childhood malignant hepatic tumors.

Purpose To evaluate the utility of transthoracic echocardiography for the early detection of subclinical cardiac metastasis in childhood malignant hepatic tumors. Patients and Methods From April 1995 until February 2000, 12 consecutive children with malignant hepatic tumor were enrolled in this study. To determine the degree of invasion of the cardiovascular system, transthoracic echocardiography was performed for all patients at the time of initial diagnosis and also at subsequent follow-up investigations every 6 months until the patient was deemed to be disease-free, or until the patient died. Results There were seven patients diagnosed with hepatocellular carcinoma (six boys, one girl) and five patients diagnosed with hepatoblastoma (three boys, two girls). Most tumors were multiple (7/12) and involved both lobes of the liver (7/12). Inferior vena cava thrombi were observed in four patients. Three patients exhibited intracardiac tumor metastasis, and lung metastasis was noted in four patients. Lung metastasis was significantly more common in children with cardiovascular involvement (4/4) compared with those without (0/8). The ages of the patient, levels of alpha-fetoprotein, and types of tumor did not differ between the two groups. Conclusions Echocardiography may be useful for the early detection of cardiovascular metastases of malignant hepatic tumors in children; this was the case for 33% of the patients in this series. The frequent occurrence of cardiovascular tumor involvement and the high degree of association between lung metastasis and cardiovascular involvement observed in this small series suggest that transthoracic echocardiography should be studied prospectively in a large series of children with hepatic tumors.

The effects of aging on AV nodal recovery properties.

KUO, C.‐T., et al.: The Effects of Aging on AV Nodal Recovery Properties. The purpose of this study was to assess the changes of AV nodal recovery properties with aging. Although in children and young adults it was found that there were age dependent changes in their AV nodal recovery properties, in the older population this information was not available. In 92 subjects (aged 16–92 years) without AV nodal disease or dual AV nodal pathway physiology, their AV nodal recovery curves were studied by delivering premature atrial extrastimuli coupled to basic atrial beats during cardiac electrophysiological study. Data were analyzed using linear regression and curve‐fitting techniques. Patients were grouped by age, group I < 40 years (n = 33), group II 40–59 years (n = 26), and group III > 60 years (n = 33). The results showed that the AV nodal recovery curve did not change significantly in the aging process except that the AV nodal effective refractory period had a positive correlation with increasing age. The latter was significantly increased in group III when compared to group I or group II. For this parameter, when patients whose AV nodal refractory period was limited by the atrial refractory period were excluded, there was still a statistically significant increase in group III compared to group II (P < 0.05): group I (n = 27): 202 ± 42 ms; group II (n =17): 197 ± 26 ms; and group III (n = 17): 224 ± 46 ms. The results suggest that the AV nodal recovery curve remains unchanged once it reaches adulthood, with the exception that the nodal effective refractory period becomes slightly longer after age 60.

Developmental Changes of Atrioventricular Nodal Recovery Properties

Atrioventricular (AV) nodal recovery properties can be studied by a periodic premature stimulation protocol performed at a slow basic rate. Developmental aspects of these properties have not been determined. The purpose of this study was to determine the developmental changes of AV nodal recovery properties. Forty-three children and young adults (male:female ratio 25:18) without AV nodal disease (aged 3.3 to 21.9 years) were studied by delivering premature atrial extrastimuli coupled to basic driven atrial beats. The individual recovery curve was fitted to the equation: A2H2 = A0H0 + exp(alpha -H1A2/tau) for H1A2 > or =theta, where A0H0 is the minimum AH interval, H1A2 is any recovery interval that exceeds the nodal effective refractory period, A2H2 is the corresponding nodal conduction time at any given H1A2, alpha is a constant, tau is the recovery time constant, and theta is the nodal effective refractory period. We found that: (1) A0H0 and alpha constant did not change significantly with age; (2) both tau (r = 0.324; p <0.05) and theta (r = 0.401; p <0.05) had a positive correlation with age; and (3) the maximum change in A2H2 with a 10-ms decrement in H1A2 was 32 ms and did not change significantly with age. Our results suggest that AV nodal recovery properties are age-dependent and both the recovery time constant and effective refractory period lengthen with age.

Renal Effects and Urinary Excretion of Prostaglandin Following Indomethacin Therapy in Premature Infants with Patent Ductus Arteriosus

Renal side effects and urinary prostaglandin were evaluated in 10 premature infants (Mean +/- SD: BW 1245 +/- 290 gm, GA 32 +/- 2.2 wks, Postnatal age 7.7 +/- 3.8 days) with significant PDA who were given one dose of indomethacin (0.3 mg/kg intravenously). There was a significant decrease in urinary output, osmolal and free water clearance after therapy. The fractional excretion of sodium, chloride, potassium, glomerular filtration rate and urinary prostaglandin E2 also decreased but were not statistically different from the baseline values. In infants who responded to indomethacin with ductus closure, their renal functions appeared to be preserved even though they had higher plasma indomethacin levels than the non-responders in whom significant changes in renal function were observed following indomethacin therapy. This observation suggested that the improved renal hemodynamics following the closure of the ductus may minimize or attenuate the renal side effects of indomethacin.