Myung Chul Hyun

Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells

Mast cells participate in allergy and inflammation by secreting inflammatory mediators such as histamine and proinflammatory cytokines. Flavonoids are naturally occurring molecules with antioxidant, cytoprotective, and antiinflammatory actions. However, effect of flavonoids on the release of histamine and proinflammatory mediator, and their comparative mechanism of action in mast cells were not well defined. Here, we compared the effect of six flavonoids (astragalin, fisetin, kaempferol, myricetin, quercetin, and rutin) on the mast cell-mediated allergic inflammation. Fisetin, kaempferol, myricetin, quercetin, and rutin inhibited IgE or phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-mediated histamine release in RBL-2H3 cells. These five flavonoids also inhibited elevation of intracellular calcium. Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation. Myricetin attenuated TNF-α and IL-6 but not IL-1β and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-κB indicated by inhibition of nuclear translocation of NF-κB, NF-κB/DNA binding, and NF-κB-dependent gene reporter assay. The pharmacological actions of these flavonoids suggest their potential activity for treatment of allergic inflammatory diseases through the down-regulation of mast cell activation.

Long-term therapeutic efficacy of lamivudine compared with interferon-α in children with chronic hepatitis B : The younger the better

Objectives: To assess and compare the long-term therapeutic response to lamivudine compared with interferon-α (IFN-α) in children with chronic hepatitis B. Methods: A total of 40 children (27 male; age, 1.3–18 y, mean, 7.7 y) with chronic hepatitis B who received lamivudine for at least 12 months were followed for a mean period of 39 (24–76) months. Their treatment efficacy was historically compared with that of 19 children (14 male; age, 2.1–17 y; mean, 10 y) who had been treated with IFN-α and were followed for a mean period of 39 (24–104) months. Therapeutic responses were compared at 2 y after the initiation of either of the treatment methods. Results: Two years after the initiation of treatment, the results for children treated with lamivudine versus IFN-α were as follows: hepatitis B e antigen (HBeAg) seroconversion occurred in 26 (65%) of the 40 children versus 7 (37%) of the 19 children, P < 0.05. In the lamivudine-treated group, the results for children treated before the age of 7 versus age >7 were as follows: HBeAg seroconversion occurred in 17 (89%) of the 19 children versus 9 (43%) of the 21 children, P < 0.01, and loss of hepatitis B surface antigen (HBsAg) occurred in 8 (42%) versus 0%, P < 0.001. Conclusions: Long-term treatment of lamivudine led to significant improvement in the seroconversion rate of HBeAg in children with chronic hepatitis B compared with IFN-α therapy. Furthermore, in preschool-age children, it led to significant improvement in the seroconversion rate of HBeAg and HBsAg compared with school-age children.

Cytokine response in pediatric patients with pandemic influenza H1N1 2009 virus infection and pneumonia: comparison with pediatric pneumonia without H1N1 2009 infection.

We investigated serum cytokine levels in pediatric patients with pandemic influenza H1N1 2009 virus (H1N1) infection‐pneumonia and in pediatric patients with pneumonia but without H1N1 infection, and examined correlations between cytokine levels and clinical/laboratory findings.

Cardiac functional evaluation using vector velocity imaging after chemotherapy including anthracyclines in children with cancer.

Background and Objectives Anthracyclines are effective drugs that are widely used in pediatric cancer treatment. Previous studies have demonstrated that exposure to low-dose anthracyclines (<300 mg/m2) induces a progressive decrease in cardiac function during long-term follow-up. The goal of this study was to assess left ventricular function using vector velocity imaging (VVI) in children undergoing low-dose anthracycline therapy. Subjects and Methods We examined 14 asymptomatic patients who had been treated with anthracyclines and had normal fractional shortening (FS) and ejection fraction (EF). In all of the patients, standard two-dimensional (2D) pulsed and tissue Doppler echocardiographic measurements were taken from an apical 4-chamber view. The peak myocardial velocity, peak strain rate (SR), peak strain, and displacement were obtained from VVI. Data were compared with 14 age-matched healthy controls. Results From the regional wall motion analysis using VVI in the left ventricle, the peak myocardial velocity and displacement of the lateral wall were increased significantly more than the septum, and there were no significant differences between the patients and the controls. Although systolic strain, and the systolic and diastolic SRs showed no significant differences between the septum and lateral wall in the controls, those of septum, in the patients, were decreased significantly more than those of lateral wall (p<0.05). In comparison with the controls, these changes in septal strain and SRs of patients were significant (p<0.05). Conclusion Anthracycline therapy, even low-dose, can induce changes in regional wall function before global dysfunction. Also, the strain and SR obtained from VVI may be useful for early detection of these changes.

Predictors of nonresponse to intravenous immunoglobulin therapy in Kawasaki disease

Purpose It has been reported that 10% to 20% of children with Kawasaki disease (KD) will not respond to intravenous immunoglobulin (IVIG) treatment. In this study, we aimed to identify useful predictors of therapeutic failure in children with KD. Methods We examined 309 children diagnosed with KD at the Kyungpook National University Hospital and the Inje University Busan Paik Hospital between January 2005 and June 2011. We retrospectively reviewed their medical records and analyzed multiple parameters in responders and nonresponders to IVIG. Results Among the 309 children, 30 (9.7%) did not respond to IVIG. They had significantly higher proportion of neutrophils, and higher levels of aspartate aminotransferase, alanine aminotransferase (ALT), total bilirubin, and N-terminal fragment of B-type natriuretic peptide than did responders. IVIG-nonresponders had a significantly longer duration of hospitalization, and more frequently experienced coronary artery lesion, and sterile pyuria. No differences in the duration of fever at initial treatment or, clinical features were noted. Conclusion Two independent predictors (ALT≥84 IU/L, total bilirubin≥0.9 mg/dL) for nonresponse were confirmed through multivariate logistic regression analysis. Thus elevated ALT and total bilirubin levels might be useful in predicting nonresponse to IVIG therapy in children with KD.

T-Helper Cytokine Profiles in Patients with Kawasaki Disease.

Background and Objectives Kawasaki disease is an acute systemic vasculitis of which pathogenesis suspected is caused by immune dysregulation. The goal of this study is to evaluate the activation pattern of T helper cell type 1 (Th1) and T helper cell type 2 (Th2) in patients with Kawasaki disease. Subjects and Methods Prospective study of 60 patients (male 36, female 24) with diagnosis of Kawasaki disease were enrolled. One hundred and eighty blood samples from these patients were collected according to the different clinical stages {before initial intravenous immunoglobulin (IVIG), 5 days after initial IVIG, 2 months after initial IVIG}. The plasma level of Th1 cytokines; interferon-gamma (IFN-γ) & interleukin (IL)-2 and Th2 cytokines; IL-4 & IL-10 were measured by enzyme-liked immunosorbent assay. Results In all patients, the plasma level of Th1 cytokines (IFN-γ, IL-2) and Th2 cytokines (IL-4 and IL-10) were markedly elevated during the acute stage of Kawasaki disease. Since then, the plasma level of all these cytokines decreased significantly along with the process of clinical stages. Regardless of the existence of coronary artery lesion or no response to initial IVIG treatment, there were no significant differences between them. Conclusion These data suggest that both Th1 and Th2 cells may be activated simultaneously during the acute stage of Kawasaki disease. Further studies are therefore required to establish the difference of activation pattern of T helper cells between Kawasaki disease and other inflammatory diseases.

Clinical features and surgical outcomes of complete transposition of the great arteries

Purpose This single-center study aimed to assess the clinical features and surgical approaches and outcomes of complete transposition of the great arteries (TGA). Methods TGA patients who had undergone surgical correction at the Kyungpook National University Hospital from January 2000 to December 2010, were retrospectively evaluated for patient characteristics, clinical manifestation, preoperative management, intraoperative findings, postoperative progress, and follow-up status. Results Twenty-eight patients (17 boys and 11 girls, mean age=10.6±21.5 days) were included and were categorized as follows: group I, TGA with intact ventricular septum (n=13); group II, TGA with ventricular septal defect (VSD, n=12); and group III, TGA/VSD with pulmonary stenosis (n=3). Group I underwent the most intensive preoperative management (balloon atrial septostomy and prostaglandin E1 medication). Group II showed the highest incidence of heart failure (P<0.05). Usual and unusual coronary anatomy patterns were observed in 20 (71%) and 8 patients, respectively. Arterial and half-turned truncal switch operations were performed in 25 and 3 patients (Group III), respectively. Postoperative complications included cardiac arrhythmias (8 patients), central nervous system complications (3 patients), acute renal failure (1 patient), infections (3 patients), and cardiac tamponade (1 patient), and no statistically significant difference was observed between the groups. Group II showed the mildest aortic regurgitation on follow-up echocardiograms (P<0.05). One patient underwent reoperation, and 1 died. The overall mortality rate was 4%. Conclusion Our study showed favorable results in all the groups and no significant difference in postoperative complication, reoperation, and mortality among the groups. However, our results were inadequate to evaluate the risk factors for reoperation and mortality owing to the small number of patients and short follow-up duration.

Acute Kidney Injury after Using Contrast during Cardiac Catheterization in Children with Heart Disease

Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr after cardiac catheterization. Until 48 hr after cardiac catheterization, there was no significant increase in serum creatinine level in all patients. Unlike urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed biphasic pattern and the significant difference in the levels of urine L-FABP between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful biomarkers to detect subclinical AKI developed by the contrast before cardiac surgery. Graphical Abstract

Wolff-Parkinson-White syndrome in young people, from childhood to young adulthood: relationships between age and clinical and electrophysiological findings

Purpose The aim of the present study was to evaluate the characteristics of electrophysiologic studies (EPS) and radiofrequency ablation (RFA) performed in subjects aged less than 30 years with Wolff-Parkinson-White (WPW) syndrome, particularly pediatric patients under 18 years of age, based on our experience. Methods Two hundred and one consecutive patients with WPW syndrome were recruited and divided to 3 groups according to age: group 1, 6 to 17 years; group 2, 18 to 29 years; and group 3, 30 to 60 years. The clinical, electrophysiological, and therapeutic data for these patients were evaluated by a retrospective medical record review. Results A total of 73 (36%) of these patients were <30 years of age. Although there were more males than females in group 2 (male:female, 31:11), there was no sex difference in group 1 (male:female, 16:15). Left accessory pathway was detected less frequently in group 1 (32%, 10/31) than in group 2 (57%, 24/42) and group 3 (63%, 81/128) (P=0.023 and P=0.002, respectively). Conclusion The present study describes several different electrophysiological characteristics in children and adolescents with WPW syndrome. Therefore, when EPS and RFA are performed in children and adolescence with WPW syndrome, we recommend that these characteristics be considered.

Comparison between Kawasaki disease with lymph-node-first presentation and Kawasaki disease without cervical lymphadenopathy

Purpose We evaluated the characteristics of patients with Kawasaki disease (KD) who presented with only fever and cervical lymphadenopathy on admission, and compared them with the characteristics of those who presented with typical features but no cervical lymphadenopathy. Methods We enrolled 98 patients diagnosed with KD. Thirteen patients had only fever and cervical lymphadenopathy on the day of admission (group 1), 31 had typical features with cervical lymphadenopathy (group 2), and 54 had typical features without cervical lymphadenopathy (group 3). Results The mean age (4.3±2.1 years) and duration of fever (7.5±3.6 days) before the first intravenous immunoglobulin (IVIG) administration were highest in group 1 (P=0.001). Moreover, this group showed higher white blood cell and neutrophil counts, and lower lymphocyte counts after the first IVIG administration as compared to the other groups (P=0.001, P=0.001, and P=0.003, respectively). Group 1 also had a longer duration of hospitalization and higher frequency of second-line treatment as compared to groups 2 and 3 (group 1 vs. group 2, P=0.000 and P=0.024; group 1 vs. group 3, P=0.000 and P=0.007). A coronary artery z score of >2.5 was frequently observed in group 1 than in group 3 (P=0.008). Conclusion KD should be suspected in children who are unresponsive to antibiotics and have prolonged fever and cervical lymphadenopathy, which indicates that KD is associated with the likelihood of requiring second-line treatment and risk of developing coronary artery dilatation.