Betau Hwang

Serial changes of serum interleukin-6, interleukin-8, and tumor necrosis factor alpha among patients with Kawasaki disease*

To determine the role of cytokines in Kawasaki disease, serial measurements of serum cytokine levels were done in 60 patients treated solely with aspirin. Coronary artery aneurysms later developed in 12 of them. The results suggest that elevated serum interleukin-6 and interleukin-8 levels during the first week of illness may be associated with a higher risk of coronary aneurysm formation.

Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis

To find new candidate loci predisposing individuals to Kawasaki disease, an acute vasculitis that affects children, we conducted a genome-wide association study in 622 individuals with Kawasaki disease (cases) and 1,107 controls in a Han Chinese population residing in Taiwan, with replication in an independent Han Chinese sample of 261 cases and 550 controls. We report two new loci, one at BLK (encoding B-lymphoid tyrosine kinase) and one at CD40, that are associated with Kawasaki disease at genome-wide significance (P < 5 × 10−8). Our findings may lead to a better understanding of the role of immune activation and inflammation in Kawasaki disease pathogenesis.

Characteristics of Kawasaki disease in infants younger than six months of age.

Background: Kawasaki disease is the leading cause of acquired heart disease in childhood. However, there are only a few reports in infants younger than 6 months. The objective of this study is to investigate the clinical and laboratory characteristics of Kawasaki disease in infants younger than 6 months. Methods: From 1994 to 2003, 120 patients with Kawasaki disease diagnosed at our institution were included. Group 1 consisted of 20 (17%) patients younger than 6 months, and group 2 consisted of 100 (83%) patients older than 6 months. Clinical manifestations, laboratory results, echocardiographic findings, treatment and outcome were compared between these 2 groups. Results: Clinical manifestations (hydrops of gallbladder: 0% versus 16%, P < 0.001) and laboratory results (white blood cell count 21,740 ± 11,706 versus 11,830 ± 4390/mm3, P < 0.001; hemoglobin 9.98 ± 1.25 versus 10.8 ± 1.37 g/dL, P = 0.015; platelet 483 ± 393 versus 355 ± 138 × 1000/mm3, P = 0.011; triglyceride 138 ± 77.5 versus 107 ± 17 mg/dL, P < 0.001) were different between patients with Kawasaki disease younger and older than 6 months, respectively. Younger infants were more likely to have incomplete presentation (35% versus 12%, P = 0.025), coronary involvement (65% versus 19%, P < 0.001), late intravenous immunoglobulin treatment and relatively poor outcome. Conclusions: Infants younger than 6 months with prolonged unexplained febrile illnesses should be suspected as having Kawasaki disease, despite the incomplete clinical presentation. Because early diagnosis and timely treatment are difficult in younger infants with Kawasaki disease because of delayed and incomplete clinical presentations, echocardiogram becomes an important implement for diagnosis. Early intravenous immunoglobulin treatment is required in view of the highest risk of coronary involvement in them.

Cytokines predict coronary aneurysm formation in Kawasaki disease patients

In this study, we measured serially the serum levels of cytokines including interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R) and tumour necrosis factor α (TNF-α) in 60 patients with Kawasaki disease (KD) and evaluated the clinical significance of these cytokines in predicting coronary aneurysm formation. Of the 60 patients, 12 were complicated with coronary aneurysm. Blood samples were collected within the 1st week after onset of fever, then once a week for the 1st month, and once a month for another 5 months. The serum levels of IL-6, IL-8, sIL-2R and TNFα were measured using an ELISA or RIA method. Our results show that the changes in serum IL-6 and IL-8 were faster than those of sIL-2R and TNFα. Within the 1st week, the serum levels of IL-6 and IL-8 were significantly higher in the patients with than in those without coronary aneurysm (P<0.001). In addition, the serum levels of IL-6 and IL-8 obtained in the 1st week were highly correlated (P<0.001) with those of C-reactive protein and erythrocyte sedimentation rate, and the serum levels of sIL-2R and TNFα were also increased at the 1st week reaching the highest level in the 2nd week. In the 2nd week, the serum levels of sIL-2R and TNFα were significantly higher in the patients with than in those without coronary aneurysm (P<0.05). These findings suggest that the serum levels of IL-6 and IL-8 obtained in the 1st week may serve as useful parameters in predicting coronary aneurysm formation in KD patients.

Isolated neonatal ductus arteriosus aneurysm

OBJECTIVE A prospective study was performed to evaluate the incidence, clinical manifestations and outcome of ductus arteriosus aneurysm (DAA) in full-term neonates. BACKGROUND Ductus arteriosus aneurysm has been considered to be a rare congenital lesion and a potentially fatal abnormality. METHODS A total of 548 full-term neonates received echocardiographic screening. RESULTS There were 48 (8.8%) patients (28 boys and 20 girls) with DAA detected by echocardiography. The maximal diameter of the DAA ranged from 6.5 to 11.2 mm (8.2 +/- 1.2 mm). All cases were asymptomatic. There were no significant differences in gender, gestational age, maternal age or Apgar score between the newborns with or without DAA. Newborns with DAA had a higher birth body weight, higher incidence of maternal gestational diabetes mellitus and more mothers with blood group A, compared with newborns without DAA (p < 0.05). Follow-up echocardiograms showed spontaneous closure of the ductus arteriosus in all patients except those without DAA. The DAA became progressively smaller after ductal closure in 33 patients (70.2%) and completely disappeared by 7 to 35 days of life. The other 14 patients (29.8%) with DAA had echocardiographic evidence of progressive formation of thrombi between the third and tenth day of life. The DAA and thrombi spontaneously disappeared in all patients by one month after birth. CONCLUSIONS There is a higher incidence of DAA with a good outcome in our series compared with previous reports. We speculate that the presence of DAA may be a normal variant of the ductal bump and part of a normal process of spontaneous ductal closure in full-term neonates.

Tourette Syndrome in Children: An Updated Review

Tourette syndrome (TS) is a common neuropsychiatric disorder in children characterized by multiple motor and vocal tics that fluctuate in severity and lasting for at least 1 year. Boys are more commonly affected than girls. Symptoms usually begin with simple motor or vocal tics which then evolve into more complex motor and vocal tics over time. Premonitory sensory urges are common in children over the age of 8 years, and these urges help distinguish tics from symptoms of other movement disorders. Common comorbidities of TS include attention deficit hyperactivity disorder, obsessive-compulsive disorder and learning difficulties. Several genes have been assessed as candidate genes for TS; environmental factors such as stress and streptococcal infections might also contribute to its etiology. The pathophysiology of TS mainly involves dysfunction of basal ganglia-related circuits and hyperactive dopaminergic innervations. A thorough history assessment and neurological examination are important for the correct diagnosis and differentiation from other movement disorders. Treatment for TS should focus on improving the patients social functioning, minimizing the impairment from cormobid disorders, and controlling tics, if they are severe. Commonly used medications for TS include a2-adrenergic agonists and atypical neuroleptics. Habit reversal therapy is an effective option for TS, and repetitive transcranial magnetic stimulation may be a promising approach for severe cases.

R1193Q of SCN5A, a Brugada and long QT mutation, is a common polymorphism in Han Chinese

Recently, Wang et al 1 reported R1193Q mutation of SCN5A in one of the seven patients with acquired long QT syndrome (LQTS) and suggested that R1193Q is a functional mutation that can increase the susceptibility to this syndrome. The mutation destabilised channel inactivation and generated a persistent late current. The investigators found that 0.2% (4/2087) of the control subjects (of whom more than 90% were white and only 0.4% were Asian) also carried the mutation, and they suggested that it may be a risk factor for LQTS in the general population. The same mutation (listed as R1192Q using SCN5A RefSeq: NM_000335) has been reported in a Japanese infant with Brugada syndrome with frequent episodes of ventricular fibrillation.2 They found that none of the 100 control subjects of Asian descent carried the variant. We have identified the same R1193Q mutation by direct DNA sequencing of SCN5A in a four generation family of Chinese descent with cardiac conduction …

Families of Children With Cancer: The Impact on Anxiety Experienced by Fathers

By using the contextual model of family stress, this study examined fathers’ family stress experience when caring for a child receiving cancer treatments. A descriptive correlational study was designed to examine the relationships between fathers’ uncertainty, sense of mastery, and anxiety. Eighty fathers were recruited from two teaching hospitals in Taiwan. A pilot study was conducted to establish the reliability and validity of the Chinese language version of the above instruments. These instruments showed an acceptable internal consistency and satisfactory construct validity. Results showed that fathers’ level of education had a significant effect on paternal anxiety. Uncertainty and fathers’ education level equal to or higher than university are good predictors of paternal anxiety, which explain 25% of the variance. The results provide insight into the paternal experience of family stress and suggest ways to improve family-centered nursing interventions and thereby establish better family well-being.

A common SCN5A polymorphism attenuates a severe cardiac phenotype caused by a nonsense SCN5A mutation in a Chinese family with an inherited cardiac conduction defect

The SCN5A mutations have been associated with a variety of arrhythmic disorders, including type 3 long QT syndrome (LQT3), Brugada syndrome and inherited cardiac conduction defects. The relationship between genotype and phenotype in SCN5A mutations is complex. Some SCN5A mutations may cause death or severe manifestations in some people and may not cause any symptoms or arrhythmias in others. The causes of these unpredictable clinical manifestations remain incompletely understood. The molecular basis of a four-generation family with cardiac conduction abnormalities was studied and whether variants in the SCN5A gene could account for the cardiac phenotypic variability observed in this family was determined. A novel mutation (W1421X) of SCN5A was identified in a four-generation family with cardiac conduction abnormalities and several cases of sudden death. Most family members who carry this W1421X mutation have developed major clinical manifestations or electrocardiographic abnormalities, both of which became more prominent as the patients grew older. However, the 73-year-old grandfather, who carried both the W1421X and R1193Q mutations, had thus far remained healthy and presented with only subtle electrocardiographic abnormalities, whereas most of his offspring, who carried a single mutation (W1421X), had died early or had major disease manifestations. This observation suggests that the R1193Q mutation has a complementary role in alleviating the deleterious effects conferred by W1421X in the function of the SCN5A gene. This report provides a good model to explain the mechanism of penetrance of genetic disorders.

Intracardiac Ultrasound Assessment of Atrial Septal Defect: Comparison with Transthoracic Echocardiographic, Angiocardiographic, and Balloon-Sizing Measurements

PurposeAccurate evaluation of the size, location and adjacent structure of an atrial septal defect (ASD) is very important in the selection of patients for further management. We directly compared the utility of transthoracic echocardiography, angiocardiography, balloon sizing, and intracardiac ultrasound (ICUS) in the detection of ASD.MethodsTwenty-one children underwent an ICUS study of ASD after routine clinical and laboratory studies. All patients had received transthoracic echocardiography (TTE), cardiac catheterization, cineangiography, and balloon sizing before the ICUS to evaluate the ASD.ResultsThere was a significant correlation between the ICUS-derived ASD diameter and the other methods (p < 0.001). The balloon-sizing diameter was estimated by the equation: TTE diameter × 1.09 + 3.9 mm. There was a good correlation between the predicted and measured balloon-sizing diameter (r = 0.963; p < 0.001).ConclusionIt is worthwhile spending a few minutes to perform ICUS during cardiac catheterization since it will provide more detailed information on and high resolution images of atrial septal morphology, especially for patients undergoing transcatheter closure by device.