Byung-Ho Choe

Electrophysiologic assessment of central auditory processing by auditory brainstem responses in children with autism spectrum disorders.

In addition to aberrant features in the speech, children with Autism Spectrum Disorder (ASD) may present unusual responses to sensory stimuli, especially to auditory stimuli. We investigated the auditory ability of children with ASD by using Auditory Brainstem Responses (ABR) as they can directly judge both hearing status and the integrity of auditory brainstem pathways. One hundred twenty-one children (71: ASD; M 58/F 13, mean age; 41.8 months, 50: control group; M 41/F 9, mean age; 38 months) were induded in the study. As compared with the values in the control group, the latency of wave V, wave I-V, and wave III-V inter-peak latencies were significantly prolonged (p<0.05) in the ASD group. The findings indicate that children with ASD have a dysfunction or immaturity of the central auditory nervous system. We suggest any children with prolonged III-V inter-peak latencies, especially high functioning children should be further evaluated for central auditory processing to set up a more appropriate treatment plan.

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.

Molecular Analysis of HLA Class ll-Associated Susceptibility to Neuroinflammatory Diseases in Korean Children

The work was done to study immunogenetic peculiarities of neuroinflammatory diseases among Korean children. A total of 13 children with neuroinflammatory diseases (8 males and 5 females; mean age 4.6±2.6 yr) were consecutively recruited. Genomic typing was performed on their HLA DRB/HLA DQB genes using PCR-SSOP/SSP techniques with gel immunoelectrophoresis. The frequencies of HLA-DR1*15 in children with acute disseminated encephalomyelitis (ADEM) (31%) and DQB1*06 in other neuroinflammatory diseases (38%) were significantly increased compared with control subjects. The frequencies of HLA-DRB3*0202 (100%), HLA-DRB1*1302 (67%), HLA-DRB3*0301 (67%), and HLA-DQB1*0301 (67%) were significantly increased in children with multiple sclerosis and the frequencies of HLA-DRB1*1501 (40%) and HLA-DRB5*0101 (40%) were significantly increased in children with ADEM. HLA-DRB1*1401, HLA-DRB3*0202, and HLA-DQB1*0502 were found in children with acute necrotizing encephalopathy. In conclusion, HLA-DR1*15 and DQB1*06 may be involved in susceptibility to inflammation in Korean children. The frequencies of HLA-DRB1*1501, HLA-DRB5*0101, HLA-DRB3*0301, and HLA-DQB1*0602 were not as high in Korean children with multiple sclerosis as in western children. However, HLA-DRB3*0202 was seen in all children with multiple sclerosis. Our data may provide further evidence that the immunogenetic background of neuroinflammatory diseases in Korean is distinctly different from the ones in western countries. Further studies are necessary to confirm this finding.

Interleukin-8 and Tumor Necrosis Factor-Alpha Are Increased in Minimal Change Disease but Do Not Alter Albumin Permeability

Aims: Minimal change disease (MCD) is the most common primary nephrotic syndrome in children. Some suggested that interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) are involved in the pathogenesis of MCD. This study was done to see changes of plasma and urinary IL-8, TNF-α, and their effects on determination of permeability of glomerular basement membrane (BM) contributed by heparan sulfate proteoglycan (HSPG). Methods: Study patients consisted of 19 biopsy-proven MCD children aged 2–15 years old. Both plasma, urinary IL-8 and TNF-α were measured. Employing the Millicell system, IL-8 and TNF-α were screened for the permeability factors. We examined whether IL-8 and TNF-α regulated BM HSPG gene expression and HS synthesis in the glomerular epithelial cells (GECs). Results: Urinary IL-8 during relapse was significantly increased when compared with that of during remission or controls (13,996 ± 2,811 vs. 2,941 ± 373, 5,331 ± 640 ng/mg·cr) (p < 0.05). Urinary TNF-α during relapse was also significantly increased (364.4 ± 51.2 vs. 155.3 ± 20.8, 36.0 ± 4.5 ng/mg·cr) (p < 0.05). Plasma IL-8 during relapse was significantly increased compared to that during remission(1.19 ± 0.62 vs. 0.51 ± 0.42 ng/ml) (p < 0.05). However, the negative results were obtained in the permeability assay using the Millicell system. No difference was seen in BM HSPG gene expression and HS synthesis in the GECs. Conclusion: Therefore, it seems that both IL-8 and TNF-α may not play a disease-specific role in the pathogenesis of MCD.

The potential for QT prolongation by antiepileptic drugs in children

Cardiac arrhythmia may be one of the major causes of sudden unexpected death in children with epilepsy. We assessed drug-induced QT prolongation to establish whether the use of antiepileptic drugs contributes to sudden unexpected death. A total of 178 children with epilepsy (93 males and 85 females, with ages ranging from 1 month to 18.9 years; mean age 7.0 +/- 4.1 years) were involved in the study. The QT intervals were manually measured and corrected using Fridericias formula (QTFc = QT/RR(1/3)). The mean corrected QT interval (QTc) of 152 children on antiepileptic drugs during the study period was 0.40 +/- 0.03 s, and for 26 age-matched, antiepileptic drug-free control patients it was 0.40 +/- 0.03 s. The mean QTc of the children with monotherapy was 0.40 +/- 0.03 s for the valproate group (n = 42), 0.39 +/- 0.02 s for the carbamazepine/oxcarbazepine group (n = 34), and 0.40 +/- 0.02 s for the topiramate group (n = 26), respectively. There was no statistically significant difference among the groups as assessed by analysis of variance. In addition, there was no significant difference between the monotherapy group (n = 109; 0.40 +/- 0.02 s) and the polytherapy group (n = 43; 0.39 +/- 0.03 s). Major antiepileptic drugs may not precipitate prolongation of the QT interval into sudden unexpected death in children with epilepsy, however further studies are required.

Efficacy of US-guided Percutaneous Cholecystocholangiography for the Early Exclusion and Type Determination of Biliary Atresia

PURPOSE To evaluate the efficacy of ultrasonographically (US)-guided percutaneous cholecystocholangiography (PCC) for early diagnosis and characterization of biliary atresia in infants with cholestatic liver disease. MATERIALS AND METHODS Institutional review board approval was obtained for this study. Parental informed written consent was obtained. From October 2003 to August 2010, 22 infants (12 male, 10 female; age range, 1-138 days) were referred to the radiology department for PCC. Indications for PCC were suspected biliary atresia at 24-hour delayed technetium 99m-diisopropyl-phenylcarbamoylmethyl-iminodiacetic acid (DISIDA) scintigraphy because no excretion was observed in the small bowel (n = 17) or when the results of the scan or liver biopsy could not be obtained within 3 days because of a delay in schedule (n = 5). A diagnosis of biliary atresia was excluded when there was contrast material visualized in the gallbladder, biliary system, and passage to the duodenum. Patients with biliary atresia underwent surgery as the reference standard. RESULTS Among the 18 patients who underwent successful PCC, biliary atresia was excluded in 13, with diagnoses as follows: total parenteral nutrition-associated cholestasis (TPNAC) (n = 6), neonatal hepatitis (n = 4), congenital syphilis (n = 1), neonatal lupus (n = 1), and congenital cytomegalovirus hepatitis (n = 1). Biliary atresia was diagnosed in five patients (four with type IIIb and one with type IIIa) and was confirmed at surgery. In four infants in whom US-guided gallbladder puncture had failed, biliary atresia (n = 2) and TPNAC (n = 2) were diagnosed. CONCLUSION PCC is a safe and useful technique for early exclusion when biliary atresia cannot be ruled out after traditional screening tests; in addition, it may be useful for preoperative type determination of biliary atresia.

Virologic responses to add-on adefovir dipivoxil treatment versus entecavir monotherapy in children with lamivudine-resistant chronic hepatitis B.

Purpose: The aim of the study was to compare the virologic response to adefovir (ADV) add-on therapy with switching to entecavir (ETV) monotherapy in children and adolescents with chronic hepatitis B (CHB) who have developed lamivudine (LAM) resistance during LAM treatment. Methods: Twenty-seven consecutive patients with CHB who had developed LAM resistance during LAM treatment were included. Of these 27 patients, 8 patients were treated with the addition of ADV to ongoing LAM and 8 patients were treated by switching to ETV monotherapy and each of these 16 patients were compared with the 11 patients who were treated by switching to ADV alone, as a historical control. Therapeutic responses to treatment were evaluated at 12, 24, 36, and 48 weeks from the initiation of therapy by measuring the decrement of hepatitis B virus (HBV)-DNA titers. Results: The therapeutic period for HBV-DNA titer decrement (>2 log10 IU/mL) was significantly shorter in both the LAM+ADV group and the ETV group than in the ADV group (P = 0.008); however, there was no significant difference between the LAM+ADV group and the ETV group. The rate of virologic response, defined as decrement in HBV-DNA titer to undetectable levels at 24 weeks, was significantly higher in both the LAM+ADV group and the ETV group than in the ADV group (P = 0.029). Conclusions: Both the LAM+ADV combination therapy and ETV monotherapy exhibited significantly more effective virologic responses compared to the ADV monotherapy in children and adolescents with LAM-resistant CHB, although there was no significant difference between the LAM+ADV group and the ETV group.

Clinical Spectrum and Prognostic Factors of Acute Necrotizing Encephalopathy in Children

This study was conducted to investigate the etiology, the clinical characteristics and prognosis of acute necrotizing encephalopathy (ANE) in Korean children. Six children (1 yr to 7 yr) patients with ANE were enrolled. They were diagnosed by clinical and radiological characteristics and their clinical data were retrospectively analyzed. In a search of clinically plausible causes, brain MRI in all patients, mitochondrial DNA studies for mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) and myoclonus epilepsy and ragged red fibers (MERRF) in four patients, and genomic typing on HLA DRB/HLA DQB genes in three patients were performed. All had precedent illnesses and the main initial symptoms included mental change (83%), seizures (50%), and focal deficits (50%). MRI revealed increased T2 signal density in the bilateral thalami and/or the brainstem in all patients. Mitochodrial DNA studies for MELAS and MERRF were negative in those children and HLA-DRB1*1401, HLA-DRB3*0202, and HLA-DQB1*0502 seemed to be significant. A high dose steroid was given to all patients, which seemed to be partly effective except for 2 patients. In conclusion, ANE is relatively rare, but can result in serious neurological complication in children. Early detection and appropriate treatment may lead to a better neurological outcome.

Changing Prevalence of Helicobacter pylori Infections in Korean Children with Recurrent Abdominal Pain.

Purpose The aim of this study is to investigate the changing prevalence rate of Helicobacter pylori infection in children, of different age groups, with recurrent abdominal pain over a 10-year period. Methods Children with recurrent abdominal pain who visited the pediatric outpatient clinic at university hospital were screened for H. pylori. Children were divided into 3 age categories of 4-5, 6-11, and 12-16 years. To study the changes in the annual prevalence rates of H. pylori infection, the study period was divided into 3 time periods: 2004-2007, 2008-2010, and 2011-2014. Urea breath test was performed for all children aged 4-16 years, with a cut-off value of 4.0‰ for children aged ≥6 years and 7‰ for children aged <6 years. Results A total of 2,530 children (1,191 boys) with a mean age of 10.0±3.0 years (range, 4.0-16.9 years) were included in the study. The total prevalence of H. pylori infection was 7.4% (187/2,530). The prevalence rate of H. pylori infection in children with recurrent abdominal pain was 8.0% (70/873) in 2004-2007, 7.7% (51/666) in 2008-2010, and 6.7% (66/991) in the 2011-2014. Nevertheless, a significant difference was observed in the prevalence rate between children <12 years old and ≥12 years of age (p=0.018). Conclusion The prevalence of H. pylori infection in Korean children with recurrent abdominal pain was 7.4%, showing no significant decrease in the last 11 years; however, the prevalence rate in children <12 years old was significantly lower than that in those ≥12 years old.

What physicians should know about the management of chronic hepatitis B in children: East side story.

Understanding the natural course of chronic hepatitis B virus (HBV) infection is very important for the management and treatment of chronic hepatitis B in children. Based on treatment guidelines, the management of HBV carriers and treatment of active hepatitis have been advancing and resulted in increased survival, as well as decreased risks of complications such as liver cirrhosis and hepatocellular carcinoma. Development of a continuing medical education (CME) program for primary physicians becomes an important responsibility of pediatric hepatologists. CME could prevent misdiagnosis and unnecessary treatment that could lead to liver complications or antiviral resistance. In addition, education of patients and their parents is necessary to achieve better therapeutic outcomes.