ABSTRACT OF INVITED LECTURES AND ORAL PRESENTATION

ABSTRACT OF INVITED LECTURES AND ORAL PRESENTATIONThursday 15 AprilPL-01PEDIATRIC RESEARCH: GLOBALCHALLENGESDavid N. CornfieldProfessor, Stanford University School of Medicine, USAEXPERIENCES AND POSITION♦ Assistant Professor of Cardiovascular Medicine, StanfordUniversity School of Medicine, Stanford, California♦ Professor of Pediatrics, Stanford University School ofMedicine, Stanford, California♦ Chief of pulmonary, allergy and critical care medicine atLucile Packard Children’s Hospital, Palo Alto, CA♦ Anne and Robert M. Bass Professor of Pulmonary MedicineEDUCATIONAL BACKGROUND:♦ Board Certification: Pediatric Pulmonary, American Board ofPediatrics (1994)♦ Board Certification: Pediatric Critical Care Medicine,American Board of Pediatrics (1996)♦ Fellowship: Children's Hospital-Denver CO (1993)♦ Residency: Children's Mercy Hospital MO (1989)♦ Internship: Children's Mercy Hospital MO (1987)♦ Medical Education: University of Wisconsin Medical SchoolWI (1986)Friday 16 AprilKLMOLECULAR INTERVENTION THERAPY:TOCILIZUMAB FOR CHILDREN WITHSYSTEMIC JUVENILE IDIOPATHIC ARTHRITISShumpei YokotaProfessor, Pediatrics, Yokohama City University, JapanSystemic juvenile idiopathic arthritis (JIA) is a subtypeof chronic childhood arthritis of unknown etiology,manifested by long-lasting systemic inflammation andcomplicated with joint destruction, functional disability,and growth impairment. Macrophage activationsyndrome is the most devastating complication, which isassociated with serious morbidity. Interleukin (IL)-6 hasbeen thought to be a pathogenic factor of this disease.Anti-IL-6 receptor monoclonal antibody, tocilizumab,was developed, and we investigated the safety andefficacy of tocilizumab in children with this disorder.The Phase II trial revealed that high-grade fever abruptlysubsided, and that inflammatory makers were alsonormalized. The optimal dose of tocilizumab forsystemic JIA was revealed 8 mg/kg at 2 weeks interval.The Phase III trial, a placebo-controlled, double-blindstudy, indicated that patients in tocilizumab group hadsustained in clinical measures of effectiveness andwellbeing, whereas most of those in the placebo groupneeded rescue treatment. The most common adverseevents were symptoms of mild infections and transientincreases of ALT. Serious adverse events wereanaphylactoid reaction, and gastrointestinal hemorrhage.Clinical and laboratory improvement in fever, sicknessbehavior, CRP gene expression, and chronicinflammatory anemia in children with systemic JIAtreated with tocilizumab indicated the possible rolesplayed by IL-6 in this inflammatory disease. Thus,tocilizumab is generally safe and well-tolerated. It mightbe a suitable treatment in the control of this disorder,which has so far been difficult to manage.54

MS1-01DELAYED TREATMENT OF GRANULOCYTECOLONY-STIMULATING FACTOR RESTORESSYNAPTIC EFFICACY AND LONG-TERMFUNCTIONAL OUTCOME AFTER NEONATALASPHYXIA IN RATSSan-Nan YangProfessor and DirectorDivision of Neonatology, Department of Pediatrics, Kaohsiung MedicalUniversity Hospital and Graduate Institute of Medicine, TaiwanOBJECTIVE: Neonatal asphyxia is a leading causeof long-term neurologic disabilities varying frommild behavioural dysfunctions to severe seizure,mental retardation, and/or cerebral palsy amongst thenewborn. At present, adjunctive therapeutic optionand ongoing research into the pathophysiology ofneuronal injury after neonatal asphyxia in thedeveloping brain are still limited. Here, we reportthat granulocyte colony-stimulating factor (G-CSF)exerts multidimensional beneficial effects involvingrecovery of synaptic efficacy, neurogenesis, andlong-term functional outcome in the developingbrain after neonatal asphyxia.METHODS: Ten-day-old (P10) rat pups weresubjected to experimental hypoxia insult. G-CSF(10-50 g/kg, single injection/day, P14-19) wassubcutaneously administered to test animals andimmunoflourecin imaging with confocal lasermicroscopy, co-immunoprecipitation withimmunobloting, whole-cell patch-clampingtechnique, and chromatin immunoprecipitation wereused to analyse synaptic alterations within thehippocampal CA1 subregion (an essential integrationarea for mammalian learning and memory) (P20).The performance of long-term learning and memorywas assessed at later ages (P37-58).RESULTS: Delayed treatment of G-CSF reversedneonatal asphyxia-induced decreases in theexpression of phosphorylated cAMP-responsiveelement-binding protein-mediated signalling,synaptic plasticity, and neurogenesis, as well asbrain-derived neurotrophic factor (BDNF)expression through epigenetic modification withtrimethylation of lysine 4 on histone H3 in bdnfpromoter gene, corresponding to long-termfunctional outcome without introducing apparentadverse effects.INTERPRETATION: Using clinically relevanttherapeutic scheme of peripherally delayed treatmentwith G-CSF is able to promote a combined beneficialmechanism involving neurogenesis with synapticplasticity recovery, and improve long-term functionaloutcome in neonatal asphyxia animalsMS1-02THE EFFECT OF CYCLIC-AMP RESPONSE ELEMENTBINDING PROTEIN (CREB) ACTIVATION ONNEUROPROTECTION AND VASOPROTECTION INTHE DEVELOPING BRAINChao-Ching HuangNational Cheng Kung University College of Medicine, TaiwanHypoxic-ischemic encephalopathy is a major cause of neurologicaldisabilities in childhood. A new approach to studying treatment for neonatalhypoxic-ischemic encephalopathy is investigating states of tolerance.Tolerance is attained by preconditioning tissue to sublethal stress, whichcauses the tissue to become more tolerant of subsequent lethal insult.Although neurons are the cellular target of preconditioning, ischemictolerance occurring on vascular cells may also contribute greatly toneuroprotection. Elucidating the protective mechanisms of preconditioningmay offer potential therapies against hypoxic-ischemic brain injury.Our study showed that in 7-day-old rat pups, ligating the carotid artery 1 hbefore hypoxia damaged the ipsilateral cerebral hemisphere; in contrast,ligating the artery 24 h before hypoxia provided complete neuroprotection.The protective effect of the 24-h artery ligation preconditioning modelrequires the activation of cAMP response element-binding protein (CREB),a transcription factor implicated in synaptic plasticity, learning and memory,and survival of the nervous system. Vessels and nerves guide each other totheir target during development, and they use common signals, such asVEGF-A, to determine the fate of neurons and endothelial cells. BecauseVEGF-A is highly expressed in neurons and vessels throughout thedevelopment, VEGF-A may be a major protector through its dual neuronaland vascular effects in the developing brain. We tested the hypothesis thatVEGF-A/VEGFR-2 signaling that leads to CREB activation is the sharedpathway underlying the protective effect of preconditioning in neurons andendothelial cells. VEGF-A, VEGFR-1, or VEGFR-2 was inhibited byantisense oligodeoxynucleotides (ODN) in vivo, and by a VEGF-Aneutralizing antibody or VEGFR-2 inhibitor in vitro. CREB phosphorylation(pCREB), and VEGF-A and VEGFR-2 expression were increased andco-localized in vascular endothelial cells and neurons in the ipsilateralcerebral cortex 24 h post-ligation. The antisense ODN blockades ofVEGF-A and VEGFR-2 decreased pCREB and reduced the protection of24-h ligation preconditioning. Furthermore, oxygen-glucose deprivation(OGD) preconditioning upregulated VEGF-A, VEGFR-2, and pCREBlevels, and protected immortalized H19-7 neurons and b.End3 endothelialcells against 24-h OGD cell death. Blocking VEGF-A or VEGFR-2 reducedCREB activation and the effects of OGD preconditioning in neurons andendothelial cells. Transfecting a serine-133 phosphorylation mutant CREBalso inhibited the protective effect of OGD preconditioning. We concludethat VEGF-A/VEGFR-2 signaling leading to CREB phosphorylation is theshared pathway underlying the preconditioning-induced protective effect inneurons and vascular endothelial cells in the developing brain.We then tested the hypotheses that selectively activating VEGFR-2 withVEGF-E, instead of activating VEGFR-1 with placenta growth factor(PlGF), phosphorylated CREB and provided neuroprotection. We found thatVEGFR-2 instead of VEGFR-1 was expressed in vessels and neurons ofpostpartum day 7 rat brain. VEGF-A and VEGF-E treatment beforehypoxic-ischemia selectively activated VEGFR-2 and CREB, and providedprotection against hypoxic-ischemic brain injury. Furthermore, selectivelyactivating VEGFR-2 with VEGF-E instead of VEGFR-1 with PlGF afterhypoxic-ischemia also provided significant neuroprotection.These findings suggest that VEGFR-2, but not VEGFR-1, is pivotal forneuroprotection in the developing brain, and that pharmacological activationof VEGFR-2/CREB signaling may be an important strategy for treatingneonatal hypoxic-ischemic brain injury.55

MS1-03RANDAMIZED TRIAL FOR THEPREVENTION OF IVH BY PROPHYLACTICIV INDOMETHACINEMasanori FujimuraPresident,Osaka Medical Center & Research Institute for Maternal andChild Health, JapanBACKGROUND: We reported at 2006 ASPR theprophylactic indomethacin (IND) to reduce the incidenceof severe intraventricular hemorrhage (IVH) in Japaneseextremely low birthweight (ELBW) infants in a largerandomized controlled tria. Our hypothesis is that thereduced incidence of severe IVH may result in improvedneurological sequela, namely prevalence of cerebral palsyat three years of age.OBJECTIVE: To compare the prevalence of cerebralpalsy around 3 years between the two groups (IND orplacebo) in a follow-up study.DESIGN / METHODS: We studied 469 infants betweenNovember 1999 and August 2003. The trial was conductedin 21 Level III neonatal intensive care units in Japan.Newborn infants with birthweights between 400-1000 gwere randomly assigned to either IND group (235 infants)or placebo groups (234 infants). Three doses of IND (0.1mg/kg/dose) starting within 6 hours of birth or placebowere given with 6-hour continuous infusion every 24hours. Neurological assessment of each infant wasconducted by qualified physicians around three years ofage.RESULTS: Of the 418 survived infants, 378 (90.4 %), 191IND infants and 187 placebo infants, were assessed aroundthree years of age. Cerebral palsy or suspected cerebralpalsy was present in 63 infants (16.3 %), 31 in IND group,32 in placebo group. There is no significant difference(p=0.87) in the prevalence of cerebral palsy or suspectedcerebral palsy or death between the IND group (53 infants,22.6%) and the placebo group (61 infants, 26.1%).Subgroup analysis was made for IVH grade three and four,and CP or death for each birth weight groups. In 400-599ggroup the number of CP or death in the IND group was 7in 22, whereas it was 18 in 27 in the placebo group. Theodds ratio is 0.23 and the IND has been shown to beeffective to reduced CP or death.CONCLUSION: 1) For the whole study subjects, therewas no difference in the number of infants with “CP ordeath” by the prophylactic use of IND compared withplacebo,; 2)The prevalence of CP in each grade of IVHshowed no evidence of difference between IND andplacebo groups; 3)The prevalence of PVL showed noevidence of difference in IND and placebo groups; 4) In asubgroup analysis, the prevalence of “CP or death” wassignificantly lower in infants with birthweight 400-599g inIND group than placebo group.Application of prophylactic IND to the smallest group ofELBW 400-599g is shown as effective in preventing thedeath or development of CP at 3-5 yearsMS1-04PROBIOTICS FOR REDUCING NECROTISINGENTEROCOLITIS IN PRETERM NEONATES-WHAT IS THE EVIDENCE?A/Prof Sanjay Patole, FRACP, DrPHDepartment of Neonatal Paediatrics,KEM Hospital for Women, University of Western Australia, PerthBACKGROUND: Results of previous systematicreviews of randomised controlled trials (RCT) haveshown that probiotic supplementation reduces the risk ofdefinite necrotising enterocolitis (NEC: RR 0.36, 95% CI0.20-0.65, p

MS2-01BURKHOLDERIA CEPACIA COMPLEXBACTERIA: THE POWER OF OPPORTUNISMDavid P. Speert, MDSauder Family Professor of Paediatrics and Head, Centre forUnderstanding and Preventing Infection in Children, University of BritishColumbia, Vancouver, CanadaBurkholderia cepacia complex (BCC) is a group ofphenotypically-related bacteria which are responsiblefor devastating infection in certain compromisedhosts. These bacteria, initially named Pseudomonascepacia, were recognized as particularly virulent insome patients with cystic fibrosis (CF) about 30years ago. Since that initial report from Toronto,other studies have also demonstrated that BCC cancause rapidly fatal, septicemic infection in CFpatients, the so-called “cepacia syndrome.” Thisillness is markedly different from that caused by themore common Pseudomonas aeruginosa, whichalmost never causes bacteraemia, and is generallyassociated with a less rapid decline in pulmonaryfunction. BCC infections in CF are particularlyproblematic because infection can spread amongpatients, even with casual social contact. BCC alsocause devastating infection in patient with chronicgranulomatous disease (CGD), a defect in phagocytickilling in which neutrophils fail to generate toxicreactive oxygen intermediates. BCC have recentlyemerged as the most common cause of fatal bacterialinfection in CGD. Common features between CF andCGD that predispose patients to BCC infection havenot been indentified but may be failure to deliverreactive oxygen intermediates to the site of infection.BCC infections are particularly challenging to treatbecause of their constitutive resistance toantimicrobial therapy, particularly aminoglycosides.The bacteria are also resistant to phagocyticnonoxidative killing, explaining their extraordinaryvirulence in CGD. Virulence determinants of theBCC have been sought by many investigators, butnone has been identified to explain the potential forinvasive and devastating infection. We and othershave recently demonstrated that BCC can grow aseither mucoid or nonmucoid. It appears that thenonmucoid variants are associated with more seriousdisease in CF than isogenic mucoid variants. Studiesare currently underway to determine the factorsassociated with the nonmucoid form that predisposeto such serious disease.MS2-02PATHOGENESIS OF MRSA PNEUMONIAAlice S. PrinceProfessor of Pediatrics, Columbia University, USAStaphylococcus aureus is an important cause ofpneumonia, especially the necrotizing pneumonias thatare being seen increasingly after influenza infection. Asthese most often occur in well children and adolescents, itis unclear exactly how or why these infections occur.Using a mouse model of pneumonia, we found that therewas significantly increased mortality in mice co-infectedwith both S. aureus and influenza, as compared to thoseinfected with either the virus or the bacteria alone. Wehave studied the role of the major virulence factor,protein A in the pathogenesis of Staphylococcalpneumonia. This bacterial surface protein binds to theTNF receptor on the surface of airway cells andstimulates the TNF cascade causing severe inflammation.In addition, protein A also binds to the EGFR andstimulates the expression of the type I interferon cascade.This signaling system is a critical component of the hostdefense against influenza. Unfortunately, the activation ofInterferon-beta and the rest of this signaling systemenhance the ability of the S. aureus to cause severepneumonia. S. aureus protein A also activates changes inthe cytoskeleton of mucosal epithelial cells. Again,through the protein A-TNFR1 interaction, RhoA GTPAseis activated resulting in the opening of the epithelial tightjunctions which enables these non-motile organisms totransmigrate across the mucosal surface and reachbinding sites in the subepithelial matrix components,establishing a nidus of infection. Thus, this surfaceprotein of staphylococci contributes substantially to theability of these bacteria to cause invasive infection in thelung.57

MS2-03PSEUDOMONAS AERUGINOSA INFECTIONIN CHILDREN: HOSPITAL V.S. COMMUNITYCheng-Hsun Chiu, MD, PhDDivision of Pediatric Infectious Diseases, Department of Pediatrics, ChangGung Children’s Hospital, Taoyuan, TaiwanPseudomonas aeruginosa has emerged worldwide asa major pathogen causing nosocomial infections suchas bloodstream infection, ventilator-associatedpneumonia, and wound infection, particularly incritical patients admitted in the intensive care units.P. aeruginosa, however, was not previouslyrecognized as an enteric infection agent, and rarelycausing life threatening events, except in patientswith immunocompromised status, cystic fibrosis(CF), and hematological, malignant, or other chronicdiseases. In Taiwan, P. aeruginosa sepsis had beendocumented to occur in the community setting, andusually affected infants without underlying diseases.Community-acquired P. aeruginosa infection couldresult in intestinal perforation, peritonitis and evenfatality in previously healthy infants, presumably dueto the initial administration of an inappropriateantibiotic regimen. The mechanism ofcommunity-acquired P. aeruginosa infection innon-CF patients has not been evaluated. In thispresentation, I will report the clinical characteristicsof community-acquired pseudomonas enterocolitisand sepsis in previously healthy infants. We alsosought to explore the microbial virulence factorsassociated with such infection in Taiwan.MS3-01POTENTIAL ANNUAL INCREASE OF PATIENTLOAD FROM CONGENITAL HEART DISEASEREQUIRING TRANSCATHETER CARDIACINTERVENTION IN EASTERN ASIAMei-Hwan WuDepartment of Pediatrics,National Taiwan University Hospital, Taipei, TaiwanTranscatheter intervention can be effectively performedin children with congenital heart diseases (CHD) to closethe abnormal shunts (secundum atrial septal defect(ASDII), patent ductus arteriosus (PDA), ventricularseptal defect (VSD)), dilate the stenosis (pulmonarystenosis) and create a pathway through the atretic outflow(pulmonary atresia with intact ventricular septum). Fromthe latest reports, though the incidence of CHD varies,the variation can be well explained by the variation of theproportion of VSD in the study cohorts. To delineate thepotential patient loads from CHD patients who mayrequire transcatheter cardiac intervention, theepidemiological data from five countries of Eastern Asia,i.e., China, Hong-Kong, Japan, Korea and Taiwan, werecollected from the literature. The population data areobtained from Unicef website. We found that theincidence of CHD in these five countries varied from6.35 to 14.77/1,000 live births. The averageCHD-specific incidence was 1.14, 1.15, 1.19, 3.82 and0.08 per 1000 live births for ASDII, PDA, pulmonarystenosis, VSD and pulmonary atresia with intactventricular septum. The proportion of perimembranousVSD in the whole VSD patients was estimated fromMACDP registration data as 25%. Potential load patientload for transcatheter intervention will be projected.These figures will provide us the basis of future planningfor medical care policy-making and medical carepersonnel training strategy-decision.58

MS3-02TRANSCATHETER CLOSURE OF VSD:CHINESE EXPERIENCEZhiwei ZHANGGuangdong Cardiovascular Institute, ChinaMS3-03STENTING OF DUCTUS ARTERIOSUS ASALTERNATIVE TO SURGICALSYSTEMIC-PULMONARY SHUNT INDUCT-DEPENDENT CYANOTIC CONGENITALHEART DISEASEMazeni AlwiInstitute Jantung Negara, MalaysiaSurgical repair of ventricular septal defects (VSD)has been clinically performed for decades andconsidered as the gold standard therapy up to date.However, it is associated with morbidity andmortality. Catheter intervention for VSD withdifferent-shaped double-disc occluders based onself-expandable materials (Amplatzer TM , Heartr TM ,Cera TM , etc.) has been clinically used for years andconsidered as alternative in selected patients.Transcatheter closure for muscular VSD (mVSD) hasshown advantages to surgical repair. As forperimenbranous VSD (pmVSD), clinical outcome,with advantages as well as disadvantages, are underintensive evaluation. From 1999 to 2007, 509 VSDpatients received transcatheter closure withAmplatzer TM (asymmetric) or Heartr TM (asymmetric,symmetric, larger-left-disc) occluders in GuangdongCardiovascular Institute. Here we shared ourtechnical experiences in catheter manipulation anddevice selection, as well as intermediate- tolong-term follow-up results. We reached conclusionsas listed below:1. Transcatheter closure of pmVSD is safe andeffective.2. Both asymmetric and symmetric occluders areequally effective for VSD closure.3. Both asymmetric and symmetric occluders havesimilar risk of major complications includinghemolysis, complete atrio-ventricular block,severe aortic or tricuspid regurgitation.4. Asymmetric occluders have increased risk ofminor complications, such as mild arrhythmiasand instant residual shunt.5. Device selection must be individualized.For many decades, systemic to pulmonary shunt (BlalockTaussig Shunt) is a widely performed palliative cardiac surgeryfor cyanotic heart disease. It allows relatively normal growthbefore corrective surgery can be performed at a later age.Advances in paediatric cardiac surgery and post operative carehas allowed complex cyanotic cardiac lesions to be repairedearly in infancy, obviating the need for palliative surgery.However a number of lesions with duct dependent pulmonarycirculation can still be corrected only at a later age and BlalockTaussig shunt remains an important part of the management.In the modern era, Blalock Taussig shunt is almost exclusivelyperformed in the neonatal period. This accounts for thesignificant morbidity of this procedure such as early shuntthrombosis and those related to thoracotomy such asdiaphragmatic paralysis and chylothorax.With advances in percutaneous coronary interventions, applyingcoronary stents to maintain PDA patency is less invasive andattractive alternative to Blalock Taussig shunt. Earlier attemptsto maintain ductal patency by formalin infiltration and use ofheated balloons have not been successful. Result of PDAstenting has been encouraging. However, there are a number ofpertinent issues. Unlike the PDA as an isolated lesion, theductus in cyanotic heart disease have a remarkable morphologicvariability. The ductus tends to arise more proximally underthe aortic arch, giving rise to a vertical PDA or occasionally itmay arise from the subclavian artery. It also tends to be longand sometimes very tortuous, rendering stent implantationtechnically impossible. The ductus in these patients may alsoinsert onto one of the branch pulmonary arteries with somestenosis at the site of insertion (“pulmonary coarctation”).Stenting the PDA in this situation accelerates and exaggeratesthis pulmonary coarctation.With regards to clinical research, issues of concern areperforming a procedure which has relatively high risk against astandard surgical procedure albeit with known seriouscomplications. The variation in ductal morphology also raisesconcerns regarding patient selection and contra-indication to theprocedure.As a new procedure, documentation and close follow up areimportant in order that safety and efficacy data can beestablished to be measured against standard surgical procedure,and to see wether it merits a place in the routine management ofcomplex cyanotic congenital heart disease.59

MS4-01EPIDEMIOLOGIC & MICROBIOLOGIC ASPECTSOF EV 71 INFECTION IN ASIA-PACIFIC AREAYhu-Chering HuangProfessor, Chang Gung University College of Medicine and Chang GungMemorial Hospital, TaiwanMS4-02MANAGEMENT CRITICAL OF EV71 INFECTION INCHINASu-Yun Qian, M.D. Prof.Beijing Children’s Hospital Affiliated with Capital Medical University, ChinaEnterovirus 71 (EV71) is a non-polio enterovirus(NPEV) and a known cause of severe poliomyelitis-likeillness, often resulting in large outbreaks worldwide.EV serotypes have traditionally been grouped accordingto neutralization serotype, gradually replaced bygenomic sequencing and thus, revised recently into fourspecies. Phylogenetically, EV71 is closely related toCoxsackie virus A16 (CAV16).EV71-associated severe neurological disease has beenobserved in many outbreaks throughout the world sincefirst reported in California, USA in 1969. During thelast 8–10 years, a shift in geographic location andfrequency of reported EV71-associated brain stemencephalitis fatalities was observed, in particular duringoutbreaks in Malaysia in 1997 and Taiwan in 1998.Several smaller scale outbreaks have been recordedfrom Western Australia, Korea, Japan and Singapore.During 2006, large-scale HFMD outbreaks in India,Thailand, Hong Kong, Malaysia and Brunei werereported and in China during 2008. Since 1998, EV71epidemics with more than 10 fatal cases occurredduring 2000~2002, 2005 and 2008.EV71 is in constant evolution with an estimatedvariation rate of 1.35 × 10 -2 substitutions per nucleotide.For phylogenetic analysis, the capsid protein VP1 isconsidered most robust for evolutionary study and threedistinct EV71 genotypes (A, B and C) were identifiedby Brown et al. The original prototype (BrCr strain) isthe sole representative of genotype A, and genotypes Bor C can be further sub-divided into genogroups B1–B4and C1–C4. During the past decade, genotypes B3, B4,C1, and B5 were reported in Malaysia, B3, B4 and C1in Singapore, B3, C2 and C1 in Australia and C4 inChina. In Japan, genotypes B3~B5, C2 and C4 wereidentified. In Taiwan the longitudinal surveillanceshowed that genotype C2 was the major strain in 1998epidemic, B4 dominated between 1999 and 2003, C4during 2004 and 2005, C5 during 2006 and 2007, andB5 in 2008. No apparent outbreak was observed in2009. The observations, when taken collectively,suggest that recombination and mutation may benefitthe spread of EV71 in the human population.The Hand, Foot and Mouth Disease (HFMD) was epidemicin China mainland between 2007 and 2009. Enterovirus 71was the most common pathogen in severe and death cases.According to the primary statistics, 61.43% of the casesconfirmed by laboratory network were EV71 (genotype C4),and it was found in 81.59% of the severe cases and morethan 95% of the death cases. The prevalence of HFMDchallenge both the garvement and medical institution onhow to better respond to the public health events.In order to monitor the prevalance of HFMD, the Ministryof Health defined HFMD as category B communicabledisease on May 2, 2008, and all the clinical cases wererequired to be registered in the Report Cards System. Aseries of measures were taken on control of the HFMDepidemic and spread, such as the patients were isolated andtreated in designated hospitals in epidemic area. Accordingto our data, no rashes or blisters were found in 8% of thedeath cases in 2008. In 2009, only 2% of the death cases hadthe same phenomenon, which may be the result of morecareful physical examination and increased awareness of thedisease. There is no specific antiviral agent or therapy forHFMD. The principles of therapy were symptomatictreatment, supportive therapy. IVIG had some effects oncontrolling the progress of the disease byimmunomodulation. It was still controversial on the use ofsteroids. The primary clinical study demonstrated that mostcritical patients with neurological complication orneurogenic pulmonary edema show insufficiencyadrenocortical function. The mortality was high when thedisease initially broke out, but the survival rate increasedafter expert teams were dispatched by the Minister of Healthto the primary hospitals for expertise support. Thegovernment and public realized the importance of PICUafter the prevalence of HFMD. Many PICUs wereestablished, and the capabilities of early recognition andtreatment of critical cases were improved. So far, thevaccine of HFMD is being developed in the laboratories.61

MS4-03MANAGEMENT OF COMPLICATED EV71INFECTION IN MALAYSIAMong-How OoiConsultant Department of Paediatrics, Sibu Hospital, MalaysiaMS4-04MANAGEMENT OF CRITICAL ENTEROVIRAL71 INFECTION PATIENTSKai-Sheng Hsieh,M.DDept. of Pediatrics, Veterans General Hospital, KaohsiungNational Yang Ming University and National Defense Medical Center, TaiwanHand, foot, and mouth disease (HFMD) is a commonchildhood exanthema, most commonly caused bycoxsackievirus A16 and human enterovirus 71 (HEV71). Inmost instances the febrile rash illness particularly that due tocoxsackievirus A16 is a benign self-limiting illness. However,since 1997 the normally considered innocuous childhoodexanthema has become a growing regional public healthproblem following frequent epidemics of death-associatedHFMD due to HEV71 across Asia. A total of 20 deathsoccurred in Sibu Hospital during the first ever documentedHEV71-associated HFMD epidemic in Sarawak in 1997. Fatalcases typically presented with a short duration of febrileillness, subtle neurological signs and deterioratedunexpectedly of fulminant cardiac dysfunction and pulmonaryoedema within hours of developing signs of cardiorespiratorydistress. Late diagnosis and late intervention were importantcontributing factors to the alarming number of fatalities.Cerebrospinal fluid (CSF) pleocytosis has been the universalfinding in almost all the fatal cases even though many have noobvious neurological signs prior to the onset ofcardiorespiratory failure.Early recognition and timely intervention in children at risk ofneurological involvement and cardiorespiratory failure is thekey to reduce acute mortality and morbidity. In Sarawak theeffort is often hindered by acute shortage of doctorsparticularly in the rural areas, where paramedics are theprincipal primary care providers. This is compounded by thechallenging geographical terrains that frequently limit thepatients’ accessibility to healthcare facilities and medicalattention. Our data showed that history of lethargy, mean peaktemperature ≥38.5°C and duration of fever ≥3 days were threeindependent risk factors predictive of CNS involvement.Screening of the three readily elicited risk factors may becarried out by paramedics with minimal training, and hasformed an integral part of HFMD patient triage at the primaryhealthcare centers in Sarawak. After the 1997 epidemic ourmanagement approach has been geared toward early diagnosisand timely intervention in children at risk of cardiorespiratoryfailure (particularly those with encephalitis andencephalomyelitis). Children with suspected CNSinvolvement are investigated with CSF examination.Intravenous immunoglobulin infusion is considered inchildren who have CSF pleocytosis, particularly in those withhigh fever, tachycardia, tachypnea and myoclonus. Our datashowed that this approach has reduced the mortality rate inchildren who had severe and potentially fatal CNScomplications seen in subsequent HEV71 epidemics between2000 and 2006 (204 [95%] of 215 cases that survived hadtimely hospital admission and intravenous immunoglobulintreatment compared to 1 (11%) of 9 cases that died (OR148.36, 95%CI 16.34–6609.04, p < 0.0001).Since the initial Outbreak of Enteroviral 71 (EV71) infectionin 1998 in Taiwan, there has been a yearly occurrence ofEV71 infection, causing variable degree of critical EV71related illness. In Taiwan, such new EV71 related disease istermed enteroviral infection but the author would use theterm EV71 syndrome & EV71 related critical illness todescribe the specific presentation of this new diseasebecause such EV71 virus, which is just one of the largeenteroviral family and such new disease is not related to theother enterovirus.It was quickly appreciated that the EV71 syndrome could beclassified into several different stages and management ofthe EV 71 syndrome can thus be made according to the stageof the patients, so called “Stage based therapy”. Using suchnew strategy, the progress could be much improved.Though stage based therapy has been accepted as thestandard approach of critical EV71 infection, the are stillsome gray area regarding the critical management of EV71Syndrome. The 1 st is how to identify the high risk patient,there should be a close collaboration between the generalpopulation and the pediatric health care system to ensureappropriate care of the children with EV71 syndrome fromthe beginning.Also the role of intravenous gammaglobulinshould be re-appraised so that valuable medical resourceswould not be spent in improper direction. The role ofmechanical cardiovascular support is another area ofcontroversy necessitating evaluation. Since theExtracorporeal Membranous Oxygen (ECMO) requires hugeamount of personnels, equipment & time to spend,appropriate policy should be made to ensure its proper use.For patients with critical EV71 syndrome, acute stage care isonly the beginning of the whole scene. Long term care forits complication should be instituted for them to have betterchance of recovery.In conclusion, EV 71 syndrome is a serious criticalcondition necessitating dedicated persconnels in pediatricspecialty (i.e.: Pediatric Intensivist),to work closely inpatients bedside to manage the rapid changing clinical statusin these patients. More effort should be made to combat thisnew EV 71 syndrome.62

FP1-01RELATIONSHIP BETWEEN CEREBRALOXYGENATION AND PHOSPHORYLATIONPOTENTIAL DURING SECONDARY ENERGYFAILURE IN HYPOXIC-ISCHEMICNEWBORN PIGLETSTakashi Kusaka 1 , Masaaki Ueno 2 ,SaneyukiYasuda 3 ,Shinji Nakamura 4 ,Kosuke Koyano 5 , KenichiIsobe 6 ,Susumu Itoh 7Faculty of Medicine, Maternal and Perinatal Center, Kagawa University,Japan 1 ;Department of Pathology and Host Defense, Faculty of Medicine,Kagawa University, Japan 2 ; Faculty of Medicine, Maternal and PerinatalCenter, Kagawa Universit, Japany 3 ;Pediatrics, Faculty of medicine Kagawauniversity 4 , Pediatrics, Kagawa University, Japan 5,6,7The aim of this study was to evaluate the hypothesisthat cerebral hemoglobin (Hb) oxygenation is relatedto phosphorylation potential during primary andsecondary cerebral energy failure in newborn infantswho have experienced birth asphyxia. Wesubjected newborn piglets to severe transientcerebral hypoxic-ischemia followed by resuscitationand examined cerebral energy metabolism by31 P-magnetic resonance spectroscopy and evaluatedchanges in cerebral Hb oxygen saturation (ScO 2 )using full-spectrum near-infrared spectroscopy(NIRS) before, during, and up to 54 hours after thehypoxic-ischemic insult. ScO 2 was significantlydecreased during the hypoxic-ischemic insult ascompared to baseline values. During secondaryenergy failure, piglets were separated based on therelationship between the ratio of phosphocreatine toinorganic phosphate and ScO 2 ; those with a negativecorrelation were less injured than those with apositive correlation. These results indicate thatchanges in ScO 2 as measured by NIRS are related tophosphorylation potential during secondary energyfailure in newborn infants who have experiencedbirth asphyxia.This study is supported by Grants-in-Aid forScientific Research (C) nos. 19591281, 15591159,and (B) no. 17390307 from the Ministry ofEducation, Culture, Sports, Science, and Technologyof Japan.[Keywords]asphyxia, cerebral hemoglobin oxygen saturation,near-infrared spectroscopy, magnetic resonance spectroscopyFP1-02THE EFFECTS OF A SINGLE DOSEDEXAMETHASONE ON HIPPOCAMPALNEURONAL DEATH, AND ITS CORRELATIONTO NESTIN EXPRESSION IN RAT PUPSYung-Chieh Lin 1 , Tseng-Shian Tsai 2 , Chun-I Sze 3 , Yuh-JyhLin 4 , Chyi-Her Lin 5Pediatrics, National Cheng Kung University Hospita. Taiwanl 1, 4, 5 , Department ofPediatrics, National Cheng Kung University, Taiwan 2 , Department of Pathologyand Cell Biology and Anatomy, National Cheng Kung University, Taiwan 3BACKGROUND: Dexamethasone (Dex) has been used inpreterm infants for hypotension, and other purposes. However,Dex administration is associated with adverseneurodevelopmental outcomes. We reported that timing of Dexadministration is critical in causing apoptotic cell death in ratpup hippocampus. In this study, we hypothesized that neuralprecursors were prone to Dex- induced cell death inhippocampal formation in rat pups.OBJECTIVE: To investigate the effects of a single dose ofDex on neuroglial apoptotic cell death in hippocampalformation in rat pups.DESIGN/METHODS: Timed-dated Wistar Albino rat pupswere used. The pups were born at 21±1 gestational days (P-0)and litters were divided into two groups. The “Dex” groupreceived one dose of Dex (0.5 mg/kg) and the control receivedan equivalent volume of normal saline (NS) intraperitoneally onpostnatal day 1 (P-1); pups were killed after 24 hours, 48 hours,4 days, and 6 days. Brain tissues were processed. Five µmtissue sections were stained with TUNEL, immunofluorescence(IF), and immunohistochemical (IHC) methods. The levels ofproteins expression and the numbers of cells in proliferationand apoptotic cells were analyzed.RESULTS: IHC stains showed that levels of nestin, tubulin,and MAP2 expression decreased with the maturation of ratpups; the number of observed ki 67 stained cells, a cell markerin the cell cycle, increased in P-1 rat pups but continuallydecreased as rat pups matured. There was a trend in reductionof nestin protein expression in the control and Dex treated (P-1)groups. Double IF stains of nestin and TUNEL revealed that ahigher percentage of TUNEL-labeled cells were also expressingnestin (Control 61±3.3; Dex 75±3.7, n=6, p=0.01) in thehippocampus of P-1 group pups sacrificed 24 hrs after Dexinjection. TUNEL staining showed that P-1 Dex treated pupshad more cells undergoing apoptosis that the control. However,double IF staining of nestin with either caspase 3 or ki 67 didnot show any significant change in percentage of cellsco-expressing caspase 3 or ki 67 and nestin between the twogroups of pups.CONCLUSION: Twenty-four hours after injection, Dexenhances apoptotic cells in rat pup hippocampal formation;these cells have shown significant co-expression of nestin,which was not observed to be significant on double IF stains ofnestin with caspase 3 or ki 67. This suggests that Dex enhancesapoptotic cell death preferentially on cells maintaining thecharacteristics of neural precursor cells.[Keywords] Dexamethasone; neonatal brain injury; hippocampus ,animal model63

FP1-03BLUNTED CIRCADIAN RHYTHMS INHEART RATE OF SMALL FORGESTATIONAL AGE INFANTS IN EARLYNEONATAL PERIODBegum Esmot Ara 1 , Bonno Motoki 1, 2 , Sasaki Naoya 2 ,Omori Yusuke 2 , Sugino Noriko 2 , Yamamoto Hatsumi 1, 2National Hospital Organization, Miechuo Medical Center, ClinicalResearch Institute 1 and Department of Pediatrics and Neonatology 2 (Japan)OBJECTIVES: Small for gestational age (SGA) infants hasbeen documented for cardiovascular poor outcomes inneonatal and adult life. Circadian rhythm has been recognizedas a prognostic marker of cardiovascular health. However,little attention has been directed at the consequences of SGAto the circadian rhythmicity. The purpose of this study is toinvestigate the characteristics and consequences of circadianrhythmicity in SGA infants.METHODS: Twenty-four-hour heart rate was continuouslyrecorded by electrocardiogram during 0-2 postnatal days. Thestudy was conducted on a total of 156 infants; 39 infants wereSGA (birth weight and height bellow < -2SDs) and 117 wereappropriate for gestational age (AGA) infants (> -1.5 to

FP1-05P2Y1 RECEPTOR-MEDIATESCALCIUM-DEPENDENT RELEASE OFGLIOTRANSMITTERS CAN INCREASEOGD-INDUCED NEURONAL INJURYHui Guo, Yu Tong, Dezhi Mu, Yi Qu, Meng Mao**Corresponding authors. Department of Pediatrics, West China SecondUniversity Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaThis work was supported by grants from the National Natural ScienceFoundation of China (No. 30772434 to Meng Mao)Numerous studies have demonstrated that neuronalCa2+ overload is a key contributor to neuronal deathinduced by cerebral hypoxia–ischemia. ATP andglutamate are important gliotransmitters, and theyare correlated with the changes of calcium signalintimately. The present study was to evaluate theeffects of gliotransmitters on OGD (Oxygen andglucose deprivation)-induced neuronal damage in ratprimary co-culture of astrocytes and neurons. Toidentify ATP or glutamate mainly contributed to theincrease of Ca2+, we detected the concentration ofextracellular Ca2+,ATP and glutamate in OGDgroup and the groups treated with OxATP (the P2X7receptor antagonist), MRS2179 (P2Y1 receptorantagonist), D-AP-5 (NMDA receptor antagonist),NBQX (AMPA receptor antagonist) respectively. Wefound that MRS significantly inhibited the increaseof Ca2+ , ATP and glutamate, and reduced theneuronal damage. These results suggest that P2Y1receptor is activated by ATP in rat astrocytes duringOGD, and P2Y1 receptor is required for thecalcium-dependent release of gliotransmitters andneuronal death. Our findings provide new insightsthat may lead to a novel therapeutic strategy ofhypoxic-ischemic brain injury by preventing therelease of gliotransmitters.[Keywords]Astrocyte; Hypoxia–ischemia; Gliotransmitter; P2Y1receptor; ATP; Ca2+ signal; neuronal cell deathFP1-06LATE PRETERM INFANTS AT RISK OFDEVELOPMENTAL DELAY AND HEALTH CAREACCRUES: EVIDENCE FROMTAIWAN BIRTH COHORT STUDYShuo-Tse Hsu 1 , Wu-Shiun Hsieh 1 , Pau-Chung Chen 2 ,Chia-Jung Hsieh 2 , Mei-Huei Chen 2 , Tung-Liang Chiang 3 ,Shio-Jean Lin 41 Department of Pediatrics, National Taiwan University Hospital and NationalTaiwan University College of Medicine, Taipei, Taiwan; 2 Institute of OccupationalMedicine and Industrial Hygiene,Taipie, Taiwan; 3 Institute of Health Policy andManagement, National Taiwan University College of Public Health, Taipei,Taiwan; 4 Department of Pediatrics, National Cheng-Kung University Hospital,Tainan, TaiwanBACKGROUND: Late preterm infants are less physiologicallyand metabolically mature compared to term infants. They are athigher risk of morbidity than term infants such as feedingproblems, respiratory tract infection, neurodevelopmentalconsequences, and rehospitalisation.OBJECTIVE: To compare the development and to delineatehealth care issues between late preterm and term infants at theage of 6 months and 18 months based on a nationwide birthcohort study.DESIGN/METHODS: A nationwide Taiwan Birth CohortStudy was launched since 2005. The data about health measuresand conditions were collected by trained interviewers usingstructured questionnaires. By using the data of Taiwan BirthCohort Study, we compared the development and to delineatedhealth care resource including infectious diseases episodes,emergency department visits and rehospitalisation between latepreterm and term infants at their age of 6 months and 18months respectively. Late preterm infant was defined as thatinfant born between 34 0/7 weeks (239 days gestation) and 366/7 weeks (259 days gestation).RESULTS: A total of 20,953 infants were available foranalysis including 19,460 (male 52.1%) term infants and 1,493(male 56.4%) late preterm infants. The late preterm infants hadsignificant developmental delay compared to those of terminfants including social smiling and rolling over from the 6months follow-up questionnaires. Their walking effortswith/without supports were also delayed compared to those ofterm infants from the 18 months follow-up questionnaires. Thehealth care costs were accrued in the late preterm infantsaccording to the increased emergency department visits andhospitalizations. The late preterm infants had more frequentepisodes of pneumonia compared to term infants, however, thewere no significant differences among the episodes of upperrespiratory infection, otitis media, and urinary tract infection, orbronchiolitis.CONCLUSIONS: The late preterm infants are at risk ofdevelopmental delay and have accrued health care costscompared to those of the term infants based on the evidencefrom Taiwan Birth Cohort Study.[Keywords]Late preterm, neurodevelopmental65

FP2-01A LONGITUDINAL MOLECULARSURVEILLANCE OF CLINICALMETHICILLIN-RESISTANTSTAPHYLOCOCCUS AUREUS ISOLATES INNEONATAL INTENSIVE CARE UNITS,1998-2007Yhu-Chering Huang, Lin-Hui Su, Tzou-Yien LinDepartments of Pediatrics and Laboratory Medicine, Chang GungMemorial Hospital, and Chang Gung University College of Medicine,TaiwanFP2-02CHARACTERIZATION OF VARIANTS IN THEPROMOTER OF BZLF1 GENE OF EBV INNONMALIGNANT EBV-ASSOCIATED DISEASESIN CHINESE CHILDRENZheng-De XIE, Ying-Kang JIN, Li-Wei GAO, Kun-LingSHENBeijing Children’s Hospital Affiliated to Capital Medical University, Beijing,ChinaBACKGROUND:Methicillin-resistantStaphylococcus aureus (MRSA) has been animportant nosocomial pathogen in our neonatalintensive care units (NICUs) since 1990s. To assessthe molecular characteristics of these MRSA strains,we conducted this study.MATERIALS: We collected MRSA clinical isolatesfrom the infants hospitalized at our NICUs from1998 to 2007, except 2002. A total of 429 clinicalisolates were selected for molecular analysis,including 10 isolates in 1998, 56 in 1999, 56 in 2000,40 in 2001, 93 in 2003, 69 in 2004, 46 in 2005, 21 in2006 and 38 in 2007.RESULTS: A total of 7 pulsotypes were identified.There were two major clones and characterized assequence type (ST) 239 (or its single locus variant)/pulsotype A (Hungary clone)/ staphylococcalchromosomal cassette (SCC) mec III orIIIA/Panton-Valentine leukocidin (PVL)-negative,accounting for 62% of the isolates, andST59/pulsotype C/SCCmec IV/PVL-negative,accounting for 26%. The former clone was dominant(> 50% of the isolates) from 1998 to 2004, becameweakened (39% of the isolates) in 2005, reached zeroin 2006, and then resurged in 2007 (18% of theisolates). The latter clone remained steady (around30%) during the study period, except in 1998, 2001and 2003 (no more than 10%). Two communityclones, characterized as ST 59/pulsotype D/SCCmecV T /PLV-positive and ST 59/pulsotype AN/SCCmecIV/PVL-negative, emerged and increased markedlyin 2007.CONCLUSION: There were two dominant MRSAclones prevailing in our NICUs between 1998 and2007. The epidemic as well as endemic clone, ST239, dominated before 2005 and was replaced by thecommunity clones, ST 59, thereafter.[Keywords]Methicillin-resistant Staphylococcus aureus,neonatal intensive care units, molecular analysisOBJECTIVES: Epstein-Barr virus (EBV) associateddiseases, such as infectious mononucleosis (IM),EBV-associated hemophagocytic lymphohistiocytosis(EBV-HLH) and chronic active EBV infection (CAEBV)are four main clinical phenotype of nonmalignant EBVassociated diseases in children. The aim of this study is toexplore the polymorphic variants of EBV BamHIfragment Z (BZLF1) promoter zone Zp in thesenonmalignant EBV associated diseases in Chinesechildren..METHODS: The Zp region was directly sequenced in206 EBV-positive DNA samples: 40 from healthcontroled cases, 88 from IM, 46 from EBV-HLH and 32from CAEBV. Type 1 or type 2 EBV was examined byPCR for EBNA2 and EBNA3C subtyping. Thechi-square test was used to assess for statisticallysignificant differences among proportions, and atwo-tailed P-value ≤0.05 was chosen as statisticallysignificant.MAIN RESULTS: Type 1 EBV was predominant in allgroups (81.3~96.7%) and there was no significantdifference in the frequency of the EBV type 1 and type 2among different group (P>0.05). Four polymorphic Zpvariants were detected, including Zp-P, Zp-V3, Zp-P4and Zp-V1. Zp-P variant was dominant in all groupsinvolved. Zp-V3 variant was more frequent in CAEBVand EBV-HLH, statistically significantly associated withCAEBV (P ≤0.01). Frequency of co-infection varants(mainly Zp-P+V3) were higer in CAEBV and EBV-HLH,compared with IM and controls.CONCLUSION: Type 1 EBV and BZLF1 Zp-P variantare predominant variants in nonmalignant EBVassociated diseases in Chinese children. Zp-V3 variantmay correlates with the developing of sever EBVinfection diseases, such as CAEBV and EBV-HLH.[Keywords]Epstein-Barr virus, infectious mononucleosis, HLH,CAEBV66

FP2-03THE POSITIVE CUT – OFF INDURATIONSIZE FOR TUBERCULIN REACTIVITY INCHILDREN WITH TUBERCULOSISINFECTION AND DISEASELuis Jr Tavu CHAN 1 , Gloriosa Catura GALINDEZ 2 ,Fe del MUNDO 3Pediatrics, Dr. Fe del Mundo Medical Center, Philippine PediatricsSociety 1 , Pediatrics, De los Santos Medical Center 2 , Pediatrics, Dr. Fe delMundo Medical Center, Philippine Pediatrics Society 3 ( Philippine)FP2-04ANTIFUNAL SUSCEPTIBILITY OFBLOODSTREAM CANDIDA ISOLATES IN ANEONATAL INTENSIVE CARE UNIT WITHROUTINE FLUCONAZOLE PROPHYLAXISTzong-Shiann Ho 1 , Shih-Ming Wang 1 , Ching-Fen Shen 2 ,Chien-Yen Huang 2 , Yuh-Jyh Lin 2 , Chyi-Her Lin 2 andChing-Chuan Liu 2, 3Department of Emergency Medicine 1 , Pediatrics 2 and Center for InfectionControl 3 , National Cheng Kung University and Hospital, TaiwanOBJECTIVE: In response to the urgent need in resolvingthe controversy as to the most appropriate cut off size forpositive tuberculin reactivity, a prospective research studywas conducted in the Philippines involving 360subjects.Children 3 months to 10 years old were included todetermine the most appropriate definition of a positivecut-off induration size for the (Mantoux 5-T.U. PPD- S)tuberculin test reaction in children with TB infection anddisease based on the statistical validity, clinical andepidemiological considerations.METHODS: Children three months to ten years old werescreened for TB using the 4 criteria for TB diagnosis inchildren; history of exposure to an infectious TB source;clinical manifestations suggestive of TB, chest radiographicevidence suggestive of TB and tuberculin skin test (PPD-SMantoux test 5 – T.U.) using 10 mm as the positiveinduration size. Based on the American Thoracic Society’sdefinition of TB disease, and the 1997 Philippine NationalConsensus on Childhood Tuberculosis classification of TB,the 360 subjects were classified into 4 main groups; Group 1(Normal Subjects), Group 2 (Tuberculosis ExposedChildren), Group 3 (TB Infection) and Group-4 (TBDisease). The true positive, true negative, false positive andfalse negative cases in this study were defined with regardthe tuberculin skin test reaction of the subject populationunder study. The sensitivity, specificity, positive andnegative predictive values and accuracy rate for 5 mm. to12 mm. induration sizes were computed. The sensitivity andspecificity of the different cut-off points were plotted in thereceiver operator curve (ROC) to illustrate the value thatwould turn the corner of the curve.MAIN RESULTS: The 8-mm. induration size revealed asensitivity of 78.36%, specificity of 89.16%, positivepredictive value (PPV) of 96.95%, negative predictive valueNPV of 48.37% and accuracy rate of 80.36%. In thereceiver’s operating curve, the 8 mm. induration was thevalue that turned the corner of the curve depicting the bestpositive cut off size. This size proved to be the bestpositive value for the PPD Mantoux test, in agreement withthe latest Philippine National TB prevalence survey.CONCLUSION: Although majority of our clinicians usethe 10 mm size as the positive cut off size, this studyshowed the 8 – mm. induration as the best value thatcould discriminate a positive from a negative tuberculinreaction in children with TB infection and those with TBdisease.OBJECTIVE: Fluconazole prophylaxis invery-low-birth-weight (VLBW, ≦1500g) neonates in neonatalintensive care units (NICU) reduces the incidence of invasivecandidiasis. However, it raises concerns for the development ofacquired fungal resistance and changes in fungal ecology. Thisstudy is aimed to evaluate the antifungal susceptibility ofbloodstream Candida isolates in a NICU with routinefluconazole prophylaxis.METHOD: A retrospective, hospital-based study wasconducted in a level III NICU which began universal six-weekfluconazole prophylaxis for VLBW preterm neonates in May,2002. All Candida isolates from bloodstream infection in theunit from May, 1999 to May, 2007 were speciated. Antifungalsusceptibilities of these species to flucytosine, amphotericin B,fluconazole, itraconazole and voriconazole were determined byATB FUNGUS 3 kit (Biomérieux corp.)MAIN RESULTS: Totally 40 Candia clinical isolates ofbloodstream infection, 15 before routine fluconazoleprophylaxis, were analyzed. C. albicans (52.5%) was the mostfrequently isolated species, followed by C. parapsilosis (30%),C. tropicalis (10%), C. lusitaniae (5%) and C. glabrata (2.5%).Fifteen (37.5%) Candida isolates were from VLBW neonates,seven (four C. albicans, two C. parapsilosis and one C.glabrata) of them were from patients with fluconazoleprophylaxis. Comparing the 5-year (2002–2007) prophylaxisperiod with the 3-year (1999–2002) preprophylaxis period, theoverall rates of nonalbicans infections were increased (26.6%vs. 60%, p=0.01). Besides, the rates of nonalbicans infectionsin VLBW neonates were comparable (25% vs. 42.8%, p=0.65).All the clinical isolates were susceptible to amphotericin B.Fluconazole-resistant Candida isolates were not found exceptone (C. tropicalis, also resistant to other azoles) in prophylaxisperiod.CONCLUSION: Universal fluconazole prophylaxis does notincrease the rate of antifungal resistance but increases thepresence of nonalabicans subspecies in bloodstream candidaisolates in NICU. Further prospective studies are needed forevaluating the long-term effects.[Keywords]Fluconazole Prophylaxis, Very-Low-Birth-Weight, NeonatalIntensive Care Unit, Antifungal Resistance, Candida BloodstreamInfection67

FP2-05EPIDEMIOLOGICAL FEATURES OFHEPATITIS B VIRUS (HBV) INFECTION INCHILDREN OF A MOUNTAINOUSMULTI-ETHNIC COMMUNITY AT THENORTHERN BORDER AREA OF VIETNAMNguyen Van Bang, Le Thi Kim Dung, Nguyen Thi VanAnh, Luong Cong Sy, Vu Thi Tuong VanHanoi Medical University/Pediatric Department, Bachmai Hospital, VietnamBACKGROUND AND AIMS: Hepatitis B virus(HBV) infection occupies a great concern in publichealth in Vietnam. This study aimed at (1) assessingthe prevalence of HBV infectin in children of amulti-ethnic community at the northern border ofVietnam, and (2) investigating factors related to HBVinfection in chldren of the community.POPULATION AND METHODS: An exploratorycross-sectional study was carried out on a populationof 482 children among 1146 of all members of 312households in a mountainous multi-ethnic community.HBV infection was determined as HbsAg (+) (ELISAtechnique). Risk factors for HBV infection in childrenwere assessed using multivariate logistic analysis.RESULTS: The overall HbsAg (+) rate in the wholestudy populution was 11.0% (126/1146). It was 9.3%(45/482) in children up to 18 years old and 12.2% inadults (81/664) (p

FP3-01AN ASSOCIATION BETWEEN ITPKC GENEPOLYMORPHISMS AND CORONARYARTERIAL LESIONS IN KAWASAKIDISEASE: FROM THEIR DEVELOPMENTAND SEVERITY TO REGRESSIONMing-Tai Lin 1 , Jou-Kou Wang 2 , Li-Chuan Sun 3 ,Jia-Feng Wu 4 , Chun-An Chen 5 , Shuenn-Nan Chiu 6 ,Mei-Hwan Wu 7Department of Pediatrics, National Taiwan University Hospita, Taiwanl 1 ;Pediatric, National Taiwan Hospital, Taiwan 2 ; Pediatrics, Cardinal TienGeneral Hospital, Taipei, Taiwan 3 ; Pediatrics, National Taiwan UniversityHospital,Taiwan 4 ; Department of Pediatrics, National Taiwan UniversityHospital, Taiwan 5 ; Pediatrics, National Taiwan University Hospital 6 ,Pediatric Cardiology, National Taiwan University Hospital, Taiwan 7FP3-02DIFFERENT GENETIC ASSOCIATION ANDGENE-GENE INTERACTION ON THESUSCEPTIBILITY AND CORONARY ARTERYLESIONS OF KAWASAKI DISEASEHo-Chang Kuo, MD, a, d Chi-Di Liang, MD, b Chih-Lu Wang, MD,PhD, f Hong-Ren Yu, MD, a, d I-Chun Lin, MD, b, d Chieh-An Liu,MD, a Jen-Chieh Chang, MS, e, g Chiu-Ping Lee, MS, e Lin Wang,MD, a, d Kao-Pin Hwang, MD, PhD, c Kuender D. Yang, MD, PhD a, dDivision of Allergy, Immunology and Rheumatology, a Division of Cardiology, b andDivision of Infectious disease; c Department of Pediatrics, Chang Gung MemorialHospital-Kaohsiung Medical Center, Taiwan. Graduate Institute of ClinicalMedical Science, Chang Gung University, Kaohsiung, Taiwan. d Genomic CoreLaboratory, Chang Gung Memorial Hospital Kaohsiung Medical Center, Taiwan. ePo-Jen Hospital, Kaohsiung, Taiwan. f Institute of Biomedical Sciences, NationalSun Yat-Sen University, Kaohsiung, Taiwan. gThe IVS1+9 G/C ITPKC polymorphism (rs28493229) has been linked to susceptibility toKawasaki disease (KD). This study examines theinfluence of this polymorphism on subsequentcoronary arterial lesions (CAL) from theirdevelopment and severity to regression. Acase-control study was conducted among 280 KDpatients with 1,127 person-years follow-up (118without any CAL from KD onset and 162 with CAL;medium/giant coronary aneurysms in 51 and small in111) and 492 healthy ethnically- and gender-matchedcontrols. Regression of CAL was defined asnormalized CAL by echocardiography withcomputed tomography conformation. We found thatthe ITPKC IVS1+9 GC and CC genotypes and the Callele frequency were higher in KD patients than incontrols (p=0.001). Among KD patients, however,the GC and CC genotypes (χ 2 = 0.23, p= 0.63) andthe C allele (χ 2 = 0.41, p= 0.52) were notover-represented among patients with CALcompared to those without. In those with CAL, the Callele of ITPKC IVS1+9 was not related to theseverity of CAL and was not associated with itsregression. We conclude that although the ITPKCIVS1+9 G/C polymorphism is a risk factor for KD,it’s not a risk for the development of CAL and itslong-term outcome.[Keywords]Kawasaki Disease, ITPKC Gene, Coronary ArterialLesions, Regression, PolymorphismBACKGROUND: Kawasaki disease (KD) is a systemic vasculitis ofunknown etiology, and primarily affects children less than 5 years ofage. Previous genetic studies identified certain candidate gene(s) for thesusceptibility and coronary artery lesion (CAL) of KD, but not able tobe validated in other studies. We have recently found that an augmentedinnate immunity with dysregulated adaptive immunity was involved inthe susceptibility of KD, and a skewed Th1/Th2 immune response wasfound in CAL of KD. We therefore hypothesize that different immunegenes are responsible for the susceptibility and CAL complication ofKD, respectively. This study was conducted to investigate whetherdifferent genetic association and gene-gene interactions on thesusceptibility and CAL of KD.METHODS: A total of 801 case (226 KD patients and 575 controls)DNA samples were subjected to a multiplex microarray for 384 singlenucleotide polymorphisms (SNPs) in 159 immune candidate genes.Genetic association was initially assessed by univariate and multivariateanalyses. Multifactor dimensionality reduction (MDR) was used toidentify gene-gene interactions.RESULTS: Thirty-one SNPs in 27 genes were associated with thesusceptibility in univariate analysis. Multivariate analysis identified 23SNPs in 22 genes were significant with susceptibility of KD. MDRanalyses of gene-gene interactions identified PDE2A (rsXXXX)interacted with CYFIP2 (rsXXXX). The MDR analysis classified the 9interactive items into the high and low risk groups, in which the highand low risk groups revealed a significant higher rate of susceptibility.(p = 9.71*10 -7 ) KD patients carried the high risk group genes hadimpaired TGF-beta response. (p=0.007). In KD patient, we found 22SNPs in 21 immune genes by univariate analysis, while 12 SNPs bymultivariate analysis showed significantly association with CAL. TheMDR analysis revealed IL2RA (rsXXXX) interact with HCG8(rsXXXX), in which the high and low risk groups revealed a significanthigher rate of CAL formation. (p=3.36*10 -6 ) KD patients carried highrisk group had higher inflammatory cytokines (IL-2, IL-6 andIFN-gamma, p

FP3-03RELATIONSHIP BETWEEN GALLBLADDERDISTENTION AND LIPID PROFILES INKAWASAKI DISEASEHae-Yong LEEProfessor, Department of Pediatrics and Adolescent Medicine, WonjuChristian Hospital, Yonsei University Wonju College of Medicine, Wonju,South KoreaFP3-04OVER-PRODUCTION OF PROTON DURINGMYOCARDIAL ISCHEMIA IS A MAJOR CAUSE OFMYOCARDIAL REPERFUSION INJURY- ANEXPERIENCE FROM THE STUDY OF DEPRESSEDYOUNGEST NEWBORN INFANTSChing-Tsuen Shen, Nan-Kung Wang, Lung-Huang LinDepartment of Pediatrics, Cathay General Hospital, Taipei, TaiwanBACKGROUND AND OBJECTIVES: While Kawasakidisease (KD) is an acute systemic vasculitis inchildren, which causes coronary arterial dilatation(CAD) and gallbladder distension (GBD). There is adearth of investigating the relationship between theseverity of KD and GBD with lipid profiles.SUBJECTS AND METHODS: A total of 80 patients with“complete KD” who were diagnosed from January2005 to May 2009 was enrolled in this study. Serumcholesterol (total, high density lipoprotein (HDL)and low density lipoprotein (LDL)), triglyceride,complete blood count (CBC), inflammation markers(erythrocyte sedimentation rate (ESR) and C-reactiveprotein (CRP) were measured at the time ofadmission during febrile period. Echocardiographyand abdominal sonogram were performed in allpatients to determine coronary arterial dilatation andgallbladder size. According to GBD, patients withKD were classified as patients with GBD andpatients without GBD. Between two groups,demographic data and clinical data were analyzed.RESULTS: The serum level of LDL cholesterol wassignificantly lower in patients with GBD (ρ=0.03)compared with patients without GBD or febrilecontrol. There was no significant difference ininflammatory indices between patients with GBDand patients without GBD. GBD was not significantrisk factor of CAD in this study (OR=2.0,95%CI=0.82-5.3, ρ=0.16).CONCLUSION: This is the first study that highlightsthe relationship between the GBD and lipidmetabolism in patients with KD. This study providesclinical insights about potential mechanismunderpinning the relationship between the GBD andlipid metabolism.[Kaywords]Kawasaki disease, Gallbladder distension; Lipidprofiles; Coronary arterial dilatation; ChildrenOBJECTIVE: Myocardial ischemia is a condition that myocardialsupply and demand of oxygen is imbalance. Under anaerobicmetabolism, mitochondria within the cardiomyocytes will producemore CO 2 , less ATP, and consequently, accumulate more protons[H+]. Re-circulation of blood to the tissue surrounding the ischemicarea will bring oxygen and neutrophils back to the penumbra area,generate interleukins, free radical, and turn on apoptosis signaling.In order to identify this relationship between the protonaccumulation and the myocardial reperfusion damage, we try to dothis study.METHODS: From 2003 to 2008, there were 118 newborn infantsdelivered at this hospital who had their one-minute Apgar score lessthan 7. Eighty-five of these 118 neonates had arterial blood gasanalysis. Fifty of these 85 neonates (58.8%) had their protonconcentration less than 10 -7.35 mol/L, (group A), the other 35neonates had their {H+} > 10 -7.36(group B). Cardiac enzymeevaluation included creatine phosphate kinase , theirMB-isoenzyme, troponin-I, lactate dehydrogenase, glutamateoxalate transaminase, and glutamate pyruvate transaminase.Twelve-lead surface electrocardiograms (EKG) were obtained in 25neonates; Seventeen of these 25 neonates were of group A, whilethe other 8 cases were of group B.RESULTS: We found that symmetric tall, inverted, or biphasic Twave, longer QRS duration, or longer QTc intervals weredemonstrated in 14 of 17 (82.35%) neonates of group A, while only2 of 8 (25%) neonates in group B. Fisher exact probability testshowed the p value was

FP3-05IRON OVERLOAD INDUCED APOPTOSIS INHL-1 CARDIOMYOCYTES VIAMITOCHONDRIA-MEDIATED CASPASE-3DEPENDENT PATHWAYSMeipian Chen 1 , Shing Chan 1 , Mo Yang 1 , Godfrey CFChan 1 , Yiu-fai Cheung 1Department of Paediatrics and Adolescent Medicine, LKS Faculty ofMedicine, The University of Hong Kong, Hong Kong, ChinaOBJECTIVES: Cardiomyopathy secondary to ironoverload is well documented in patients withbeta-thalassaemia major. Nonetheless, the underlyingmechanisms remain to be defined. We hypothesize thatiron overload contributes to cardiac dysfunction byinducing apoptosis of cardiomyocytes.METHODS: To test the hypothesis, the apoptoticeffects of iron on the contracting HL-1 cardiomyocytes,established from AT-1 mouse atrial cardiomyocytetumour, were determined in-vitro. After 72 hours ofexposure to FeCl 3 , HL-cells were examined using flowcytometry for apoptosis as assessed by annexin V /propidium iodide (PI), active caspase-3, and JC-1staining.MAIN RESULTS: By annexin V / PI staining, thepopulation of apoptotic cells was shown to increase in adose-dependent manner with iron loading (150-600 μM,n=2 to 5), with significant increase being found at 300μM (p

FP4-01A 4 YEARS OF PEDIATRIC INJURYSURVEILLANCE REVIEW BYCOMPUTERIZED EMERGENCYBASED-MODEL AT RAMATHIBODIHOSPITAL, THAILANDSakda Arj-ong, Nongluck TechajareonPediatric Emergency Division, Department of Emergency MedicineFaculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok,Thailand 10400INTRODUCTION: According to the WHO Report 2002,pediatric injuries was the sixth leading cause of morbidityand mortality in childhood, there have few studies ofpediatric injury surveillance & research in Thailand. Weevaluated the type of pediatric injuries encountered in theemergency room of Ramathibodi hospital, which tertiarycare hospital to study the incidence and surveillance ofpediatric injury according to age group represent theurbanized pediatric injury incidence.OBJECTIVES & MATERIALS: Retrospective reviewswith Thai-Computerized-Emergency-Based-Model withObject-Related-Injuries-Surveillance-Survey, injured-childin ER at Ramathibodi Hospital, 0-14 years old during Jan2003 to Dec 2006 were analyzed into two categories, Firstis demographic data and second is clinical data, triage,injured-types, aged-group-relate, disposition, PediatricTrauma Score (PTS)/Revised Trauma Score (RTS) whichwere calculated each items into score, analyses insubcategories for effectiveness of ER management.RESULTS: 2,319 cases of Pediatric injured, male 61.84%, female 38.16%, mean age is 6 years old, 0-5 year’sold-group has highest incidence/risk for injury. 65.3percent is in triage categories level 2. The fifth top ranksare animal bite & string, fall, struck by against,transportation and cut injured. Almost of injured visits areminor trauma, which can observe and safety to discharge,Sexual abuse still have a higher trend than the physicalabuse and neglect, usually abuse by known person. ThePTS/RTS are not valuable for management due to minorinjury case mixed in tertiary center.CONCLUSIONS: The 4 years of retrospectivesurveillance reviews was demonstrated the trend ofpediatric injury still high, different incidence between agegroup and developmental aspects. The five top ranks ofinjuries show different incidences with western country.The future prospective surveillance and multisite,multicenter are need to reflect all incidence of pediatricinjury in Thailand.[Keywords]Pediatric Injury, Injury Surveillance, RTS, PTS,Computerized Emergency Based-Model, Injury DatabasePrototypeFP4-02DO CARGIVERS IN SAUDI ARABIA GIVE THEIRCHILDREN WITH FVER THE ACCURATE DOSEOF ACETAMINOPHEN?Fawaz Al Enazi, Nahar Alrewali, and Mohammed Al OmarKing Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaOBJECTIVES: Fever contributes to significant visits ofEmergency Department (ED). Through our clinicalobservation some children were not given the accuratedose of acetaminophen. We decided to know whethercaregivers give their children with fever the accuratedose of acetaminophen and what are the factorsassociated with dose inaccuracy.METHODS: A cross-sectional study of 200 caregiverswho gave acetaminophen to their children with fever inthe preceding 24 hours was interviewed.MAIN RESULTS: Enrolment was 89 %. Seventy-sevenof caregivers (43%) gave an accurate dose ofacetaminophen. Fifty-three (30%) gave aninfratherapeutic and 48 (27%) gave supratherapeuticdoses. Caregivers who gave the accurate doses weremore likely to space acetaminophen doses less than4-hourly (RR 0.63 P < 0.04, 95% CI= 0.37 to 1.07).Patients receiving acetaminophen per rectum had asignificantly greater rate of supratherapeutic doses 9/28(32%) versus 39/149 (26%), respectively (95% CI= 0.14to 0.48). Sixteen caregivers (9%) gave more than fivedoses per 24 hours (RR1.11, 95%CI=0.74-1.67).Physicians and pharmacist were more likely to be thereferences of an inaccurate doses (RR1.2995%CI=0.95-1.75) and (RR 1.27 95%CI=0.75-2.18)respectively. Fathers and Caregivers with an educationlevel of intermediate and secondary levels were morelikely to give inaccurate doses (RR1.15,95%CI=0.76-1.73), (RR1.28 95%CI=0.91-1.79) and (RR1.20, 95%CI=0.92-1.57) respectively.CONCLUSION: Large percentage of caregivers givesan inaccurate dose of acetaminophen. Fathers,intermediate and secondary school level of education,physicians and pharmacists as a references, were morelikely to give an inaccurate doses, suggesting educationmay be valuable in ameliorating this common problem.[Keywords]Children, fever, acetaminophen, dose accuracy72

FP4-03THE DEFECTIVE INNATE IMMUNERESPONSES IN ASTHMATIC MICEShen-Hao Lai, Sui-Ling Liao, Kin-Sun WongDepartment of Pediatrics, Chang Gung Memorial Hospital, TaiwanFP4-04ROLE OF MAP KINASE SIGNAL PATHWAY INHYPEROXIA-INDUCED LUNG INJURYXU FENGICU, Children's Hospital of Chongqing Medical University, ChinaOBJECTIVE: Respiratory viral infections werealready known to closely relate with theexacerbations of asthma in children and adults.Defective immune response of the asthmatics washypothesized to play an important role in theseexacerbations. We then further evaluate the anti-viralimmunity in mice with allergic airway disease.METHODS: We used a model of allergic airwayinflammation in which OVA sensitized mice werechallenged by daily OVA nebulization, followed byintranasal inoculation with either respiratorysyncytial virus (RSV) or human metapneumovirus(hMPV). Type I interferon (IFN), cytokines andchemokines were measured in bronchoalveolarlavage fluid (BALF) along with peak viral titers.Lungs were also collected to analyze the expressionof signal transcriptors of type I INF.MAIN RESULTS: Compared to the control mice,RSV-infected allergic mice had significantlyincreased viral replication in their lungs. Thisincrement of virus was associated with the decreasedlevels of type I INF in BALF. On the contrary, thehMPV-infected sensitized mice didn’t have theseresponses. Although significantly increasedexpression of Toll-like receptor (TLR3) were foundin the lungs, the key signal transcriptor, interferonregulatory factor 3 (IRF3), was also significantlysuppressed in the RSV-infected allergic mice.CONCLUSION: The defective anti-viral innateresponse was observed in allergic airway diseases.Suppressed expression of INF signal transcriptorcontributed to decreased production of type I INF.These might resulte to the acute viral exacerbationsof allergic airway diseases.[Keywords]Innate immunity, mice, asthma, respiratorysyncytial virus, human metapneumoviruOBJECTIVE: To explore distributions and expressions ofERK, JNK, p38 MAP kinas in lung tissues and roles of MAPkinases on hyperoxia-induced lung injury development withsignal pathway inhibitors.METHODS: Sixty Wistar rats aged 3 weeks old wererandomized to 10 groups with 6 rats in each: room-airgroup(A), hyperoxia exposure 3,7,14 days groups (O 3 、O 7 、O 14 ) , hyperoxia 7 d+ PD98059 group(O 7 +PD)、hyperoxia7 d +SB203580 group ( O 7 +SB ) , hyperoxia 7 d +SP600125 group(O 7 +SP)and room-air +inhibitors groups.Rats were received i.v injection of PD98059(0.3mg/kg/dose, 1 dose)and SB203580(0.2 mg/kg/dose,1 dose)and injected with SP600125 (15 mg/kg/dose, 1 dose)intraperitoneally. Lung pathology examined by lightmicroscopy, lung wet/dry ratio (W/D) and protein level inBALF and permeability coefficient was evaluated.Thelocation and quantity of MAP kinases protein were detectedby immunohistochemistry and Western blot analysisrespectively.RESULTS: Lung injury in Hyperoxia exposure groups weredeveloped compared with room-air group, W/D and proteinlevel in BALF and permeability coefficient in O 7 and O 14groups increased than those in control group(P

FP4-05FACTORS ASSOCIATED WITH DEATHAMONG UNDER-FIVE CHILDREN WITHPNEUMONIA IN AN URBAN DIARRHOEATREATMENT CENTRE, DHAKA,BANGLADESHMohammod Jobayer Chisti 1 2 , Mohammed AbdusSalam 1 , Pradip Kumar Bardhan 1 , Tahmeed Ahmed 1 ,Abu Syed Golam Faruque 1 , Sophie La Vincente 2 4 ,Colin F Robertson 3 4 , Trevor Duke 2 41 Clinical Sciences Division (CSD), International Centre for DiarrhoealDisease Research, Bangladesh (ICDDR,B); 2 Centre for International ChildHealth (CICH), Royal Children’s Hospital, Department of Paediatrics, TheUniversity of Melbourne; 3 Respiratory Medicine, Royal Children’s Hospital,Department of Paediatrics, The University of Melbourne 4 MurdochChildren’s Research Institute (MCRI)OBJECTIVES: To evaluate the clinical and thesocio-demographic predictors of deaths from pneumoniaamong under-five children with diarrhoea.METHODS: We prospectively enrolled all children youngerthan 5 years who were admitted to the Special Care Unit(SCU) of the Dhaka Hospital of ICDDR,B with pneumoniaalong with diarrhoea during September through December2007. Pneumonia was diagnosed according to WHOguidelines for acute respiratory infection (ARI). Treatmentinvolved giving oxygen if oxygen saturation was poor,broad-spectrum antibiotics as per the hospital protocol,intravenous or oral rehydration fluids if dehydrated or inshock, and diet. Out of the total 198 children enrolled,characteristics of children with fatal outcome (n=24) werecompared with those who survived (n=174).MAIN RESULTS: In univariate analysis the risk factors fordeath in children with pneumonia were: kwashiorkor (25% vs.10%; p = 0.04), clinical sepsis (79% vs. 49%; p = 0.010), poorperipheral perfusion as indicated by uncountable/absent radialpulse (29% vs. 7%; p = 0.003), low systolic (62.0 ± 41.0 vs.98.4 ± 28.4: p = 0.001) and diastolic (27.5 ± 21.9 vs. 56.7 ±19.4: p < 0.001) blood pressure (mm of Hg), low SPO2 (%)on admission (80.0 ± 12.0 vs. 89.1 ± 10.0: p = 0.001),immature neutrophils (%) in the peripheral blood [0.0 (0.0,2.0) vs. 0. 0 (0.0, 0.0): p = 0.031], and renal failure asindicated by median (interquartile range) value of serumcreatinine (micromol/L) [156.5 (119.3, 264.3) vs. 75.0 (67.1,116.3): p = 0.026]. However, after adjusting for thecovariates by logistic regression, risk factors for a fataloutcome were severely underweight (OR 5.17, CI 1.21-22.02,p = 0.026), hypoxaemia (OR 17.52, CI 1.92-159.97, p =0.011), severe sepsis (OR 8.68, CI 1.81-41.52, p = 0.007) andlobar consolidation (OR 11.90, CI 2.30-61.58, p = 0.003).Metabolic acidosis was less common (OR 0.85, CI 0.75-0.97,p = 0.012).CONCLUSION: Our study identified severe malnutrition,hypoxaemia, severe sepsis, and lobar consolidation asindependent factors for deaths among children admitted withdiarrhoea and co-existent pneumonia. Identification of thesefactors and initiation of their appropriate managment couldhelp to prevent deaths among such children.[Keywords]Children; diarrhoea; death; hypoxaemia;pneumonia; under nutritionFP4-06EFFICACY OF INTRATRACHEAL ADMINISTRATIONOF MEROPENEM IN AN ANIMAL MODEL OF ACUTELUNG INJURYMei-Jy Jeng, Wen-Jue Soong, Pei-Chen Tsao, Chia-FengYang, Shih-Yun Chiu, Yu-Sheng Lee, Ran-Bin TangInstitute of Emergency and Critical Care Medicine, School of Medicine, NationalYang-Ming University; and Department of Pediatrics, Children’s Medical Center,Taipei Veterans General Hospital, Taipei, TaiwanOBJECTIVE: To evaluate the efficacy of intratrachealadministration of meropenem using perfluorochemical (PFC) asa drug vehicle in an animal model of acute lung injury.METHODS: Eighteen newborn piglets were anesthetized,ventilated, injured with repeated saline lung lavage to induceacute lung injury, and grouped randomly into one of three studygroups: (1)Intravenous (IV) group (n = 6): intravenous injectionwith meropenem (20 mg/kg); (2)Intratracheal PFC (IT-PFC)group (n = 6): intratracheal instillation with the mixture of PFC(PP4, F2 Chemicals, 10 mL/kg) and meropenem (20 mg/kg);(3) Intratracheal normal saline (IT-NS) group: intratrachealinstillation with the mixture of saline (10 mL/kg) andmeropenem (20 mg/kg). Blood samples were obtained at 0, 15,30, 60, 120, 180, 240, 300, and 360 min for checking serumlevels of meropenem and arterial blood gas analysis. Lungtissues were obtained for testing meropenem contents afterexperiments. Peak inspiratory pressure (PIP) and lungcompliance (C L ) were also checked every 30 min.MAIN RESULTS: Animals of IV group showed the highestserum levels of meropenem (15 min: 17.8 μg/mL, 60 min: 7.7μg/mL, 360 min: 0.6 μg/mL), and animals of IT-PFC and IT-NSgroups had similar serum meropenem concentrations: (IT-PFC:15 min: 5.6μg/mL , 60 min: 4.8 μg/mL , 360 min: 0.3 μg/mL ;IT-NS group: 15 min: 6.2 μg/mL, 60 min: 5.5 μg/mL, 360 min:0.6 μg/mL ). The meropenem contents in lung tissue werehighest in IT-PFC group (1.25 ± 0.90 μg/g tissue at thedependent site and 0.23 ± 0.16 μg/g tissue at the non-dependentsite, but they are all undetectable in IT-NS and IV group. Inaddition, animals of IT-NS group had the highest PIP andlowest C L during the experimental 4h. During the experiments,there was no significant difference in the blood gas changesamong the three study groups.CONCLUSION: Intratracheally instilling the mixture ofmeropenem and PFC or normal saline is a safe way toadminister the antibiotics to injured lungs. The use of PFCliquid to carry meropenem into the lungs provides better drugdepositions than intravenous injection or intratrachealinstillation with saline. Therefore, the technique of intratrachealinstillation of meropenem and PFC liquid may be an effectiveway to treat patients with meropenem sensitive pulmonaryinfections in acute lung injury in the future.[Keywords]acute lung injury, intratracheal administration, meropenem,perfluorochemical74

FP5-01ALK GENE ABERRATIONS IN PEDIATRICSOLID TUMORSJunko Takita 1,2,3 , Riki Nishimura 1, , Masashi Sanada 3 ,Kentaro Ohki 1, , Motohiro Kato 1 , Yuyan Chen 1 ,Hirokazu Kanegane 4 , Hajime Okita 5 , JunichiroFujimoto 5 , Akira Kikuchi 1 , Takashi Igarashi 1 , YasuhideHayashi 6 ,Seishi Ogawa 21 Dept. of Pediatrics, 2 Dept. of Cell Therapy and Transplantation Medicine,3 Cancer Genomics Project, Univ. of Tokyo, 4 Dept. of Pediatrics, Univ. ofToyama, 5 Dept.of Developmental Biology, National Research Institute forChild Health and 6 Gunma Children’s Medical Ctr.(Japan)OBJECTIVES: Anaplastic lymphpma kinase (ALK) is a receptortyrosine kinase which is constitutively activated by chromosomaltranslocations in human cancers, including a subset of malignantlymphoma, lung cancer, as well as inflammatory myofibroblastictumor. Previously we and other groups demonstrated thatconstitutive activation of the ALK kinase is also found inadvanced sporadic as well as familial neuroblastoma cases, inwhich ALK undergoes gene mutations and/or amplifications.Although recent molecular and immunohistochemical studies haveshown that the frequent expression of ALK in pediatric solidtumors, their roles in the pathogenesis of pediatric solid tumors arestill elusive.METHODS: To elucidate the involvement of ALK abnormalitiesin the pathogenesis of other pediatric solid tumors, ALKexpression and gene mutations/amplifications were examined byRT-PCR and direct sequencing of PCR-amplified genomic DNAas well as SNP array-based copy number analysis. In total, 203tumor samples were analyzed, including 102 of Ewing sarcomafamily of tumors (ESFT), 70 of rhabdomyosarcoma, 18 ofmalignant rhabdoid tumors and 13 of medulloblastoma.MAIN RESULTS: ALK was expressed in all samples of ESFTand medulloblastoma examined. Seventeen out of 29 (59%)rhabdomyosarcoma samples showed ALK expression, whereas theexpression was detected in only 2 out of the 8 malignant rhabdoidtumor cell lines. High-grade amplifications involving the ALKlocus and novel missense mutations within the tyrosine kinasedomain were detected in 6 samples. The mutant ALK proteinswere constitutively phosphorylated and showed an increasedkinase activity. NIH3T3 cells stably expressing mutant kinaseshowed increased colony formation in soft agar compared withthose expressing the wild-type protein. Furthermore, RNAinterference-madiated ALK knockdown resulted in reduced cellproliferation of an ESFT cell line harbouring a novel ALKmutation as well as SK-N-SH neuroblastoma cells with F1174Lmutation. In addition, an ALK inhibitor induced suppression ofcell growth in these ALK-mutated or –amplified cell lines withpotent suppression of downstream signalling, including AKT,ERK and STAT3.CONCLUSION: Our findings provide new insights into thepathogenesis of pediatric solid tumors and also indicate thatALK-mediated signaling may be a potential therapeutic target forthese tumors.[Keywords]ALK, Pediatric solid tumors, SNP arrayFP5-02IKZF1 DELETION DETECTED BY QUANTITATIVE ASSAY OFDELETION OR DUPLICATION GENOTYPE BY CAPILLARYELECTROPHORESIS AND IKZF1 DELETION WASASSOCIATED WITH POOR PROGNOSIS IN CHILDHOODB-CELL–PROGENITOR ACUTE LYMPHOBLASTICLEUKEMIA (ALL)Yung-Li Yang 1,2 , Chia-Cheng Hung 3 , Jiann-Shiuh Chen 4 , Kai-HsinLin 2 , Shiann-Tarng Jou 2 , Chih-Cheng Hsiao 5 , Sung Liang Yu 6 ,Shu-Wha Lin 6 , Yi-Ning Su 3 , Dong-Tsamn Lin 1,21 Department of Laboratory Medicine, 2 Department of Pediatrics, 3 Department ofMedical Genetics, National Taiwan University Hospital, 6 Department of ClinicalLaboratory Sciences and Medical Biotechnology, College of Medicine, NationalTaiwan University, Taipei, Taiwan. 4 Department of Pediatrics, National ChengKung University Hospital, Tainan, Taiwan. 5 Department of Pediatrics, ChangGung Memorial Hospital-Kaohsiung Medical Center, College of Medicine, ChangGung University Kaohsiung, Taiwan.OBJECTIVE: Despite the current risk-directed therapy, about 15-20%of pediatric patients with acute lymphoblastic leukemia (ALL) have arelapse. Recent genome-wide analyses have identified that the deletionof IKZF1 was associated with a very poor outcome in B-cell–progenitorALL. We want to develop a rapid and cheap method to detect IKZF1deletion in our ALL patients and investigate its prognostic impact in ourcohort.METHODS: The study included 191 patients B-progenitor ALL fromfour different medical centers in Taiwan. The patients were treated withTPOG-ALL-93 (Taiwan Pediatric Oncology Group),TPOG-ALL-97-VHR or TPOG-ALL 2002 protocols and followed-upfor 2 to 139.3 (median 56.5) months. We have developed a sensitiveand simple multiplex quantitative PCR coupled with capillaryelectrophoresis for accurate allele dose determination. Event-freesurvival (EFS) and overall survival (OS) were calculated using theKaplan-Meier method, and the log-rank test was used to comparedifferences between survival curves. The Cox proportional hazardsmodel was used to identify independent prognostic factors with respectto EFS and OS.MAIN RESULTS: Twenty patients (20/191=10.4%) with IKZF1deletion were detected. Most of the deletion was within the exons 3-6,which was compatible with previous reports. The 5- and 10-year EFS(±s.e.) rates in patients with IKZF1 deletion were 26.5±10.1% and26.5±10.1%, respectively, whereas in patients without IKZF1 deletion,5- and 10-year EFS rates were 75.3±3.4%. The 5- and 10-year OS(±s.e.) rates in patients with IKZF1 deletion were 49.0±13.4% and32.7±16.0%, respectively, whereas in patients without IKZF1 deletion ,5- and 10-year OS rates were 75.4±3.4%. Patients with IKZF1 deletionhad inferior EFS (p

FP5-03COPY NUMBER VARIATION ANDTRANSCRIPTOME ANALYSES ONPEDIATRIC BRAIN TUMORS REVEALNOVEL PROGNOSIS FACTORS AND RAREINI1 MUTATION IN TAIWANESE ATYPICALTERATOID/RHABDOID TUMOR ANDMEDULLOBLASTOMASHsei-Wei Wang 1,2,3 , Donald Ming-Tak Ho 4 andTai-Tong Wong 51 Institute of Microbiology and Immunology, 2 Institute of Clinical Medicine,3 Institute of Biochemistry and Molecular Biology, National Yang-MingUniversity; 2 VGH Yang-Ming Genome Research Center, NationalYang-Ming University; 3 Department of Education and Research, Taipei CityHospital; 4 Department of Pathology and Laboratory Medicine, TaipeiVeterans General Hospital; 5 Department of Neurosurgery, NeurologicalInstitute, Veterans General Hospital Taipei, Taipei, TaiwanOBJECTIVE (AIM OF THE STUDY): Atypicalteratoid/rhabdoid tumor (AT/RT) is a highly malignant pediatricCNS tumor with the worst prognosis among embryonal tumors(such as medulloblastoma (MB)) or pediatric germ cell tumors(GCTs, such as germinoma (good prognosis) andnon-germinomatous GCT (NGGCT; worse prognosis)). Previousstudies showed deletion or mutation of the INI1 gene and the lackof INI1 protein expression in 100% to 84% of studied AT/RTscases. The underlying mechanisms of different incident andprognosis of various pediatric brain tumors are unclear.METHODS: 10 AT/RT, 24 MB, 7 germinoma and 15 NGMGCTcases were subjected into whole genome copy number variationand transcriptome analysis. The Agilent Human miRNA V2Microarray chip, Affymetrix TM HG-U133 Plus 2.0 whole genomearray, Illumina Human610-Quad Beadchip, and Agilent HumanGenome CGH Microarray Kit 244A chip system were used.Filtrated features were subjected into Systems biology analysisand copy number variation detection for finding unique functionalmodules and aberrant chromosome regions in each pediatric braintumors.MAIN RESULTS: We observed genes responsible for cellproliferation, Ras signaling pathway (NOTCH2 and IQGAP1) andcell survival are abundant in AT/RTs, while genes associated withcell cycle checkpoint and DNA damage repair in MBs. CNSgerminomas also express more DNA damage checkpoint genes(CHEK2 & HUS1), as well as stemness genes (such as OCT4,NANOG and KLF4. Genes associated with neuron differentiationare relative abundant in NGMGCTs. Novel prognosis markerswere identified to divide primary MB patients into high- andmoderate-risk prognostic groups. Array CGH analysis onTaiwanese AT/RT samples revealed no aberration around the INI1gene at 22q11.2. Direct DNA sequencing showed no INI1 genesequence alternation in 7/9 of AT/RTs, and point mutation in onlyone allele of 2 cases, of which only one case have proteinmutation. IHC staining showed INI1 protein is still expressed in55.6% of examined cases. INI1(-) patients possessed worseprognosis.CONCLUSION: This study integrates molecular profiles withclinical observations and provides the underlying pathogenesismechanisms for different pediatric brain tumors. Our data revealnovel pathogenesis mechanisms, prognosis markers and candidatedrug targets. INI1 mutation is rare in Taiwanese patients, making itan erroneous marker for the diagnosis of AT/RT in Taiwanese, andmaybe Asian, cases.FP5-04BEHAVIORAL OUTCOME OF ACUTELYMPHOBLASTIC LEUKEMIA SURVIVORS INNATIONAL UNIVERSITY OF MALAYSIAMarina M.S., MD 1 , Hamidah A., MD 1 , Zarina A.L., MD 1 ,Rahman Jamal, MD, Vijayalakshmi R. 1 ,Rahman Jamal,MD 1 , Azmi M.Tamil, MD 21 Department of Pediatrics, Faculty of Medicine, National University of Malaysia,Kuala Lumpur, Malaysia; 2 Department of Public Health, Faculty of Medicine,National University of Malaysia, Kuala Lumpur, MalaysiaOBJECTIVES: To determine the behavior outcome ofAcute Lymphoblastic Leukemia (ALL) survivors thatcompleted treatment in University Kebangsaan MalaysiaMedical Centre (UKMMC) from 2000 to 2007.METHODS: This is a case-control study involving ALLsurvivors who were 2 years from completing treatment(chemotherapy only). They received the UK ALL 97/98(Regimen A or B) or Relapsed protocol.57 ALL survivors(age 6 to 18 years old) were compared to a group ofhealthy school children (n = 221). Parents completed theChild Behavior Check List (CBCL) questionnaire toassess behavior functioning.MAIN RESULTS: There were no differences ininternalization, externalization and total scores. However,ALL survivors scored higher in 2 of the sub-scales for“anxious/depressed” and “somatic” (p values were 0.019and 0.022 respectively). The other sub-scales were notsignificant. When the different ethnic groups werecompared, ethnic Malay ALL survivors had significantscores in the sub-scale “anxious” (p = 0.034). Otherfactors analyzed including gender, mean socio-economicstatus, age at diagnosis, age at study entry, types ofchemotherapy, type of ALL classification were notsignificant.CONCLUSION: There is evidence of subtle butsignificant behavioral problems in survivors of childhoodALL. CBCL questionnaire is a valuable tool to be usedby clinicians during follow-up of these children.Long-term follow-up of ALL survivors is warranted, withadded attention to psychosocial morbidities.[Keywords]Acute lymphoblastic leukemia, behavior outcome, ChildBehavior Check List[Keywords]AT/RT, Medulloblastoma, INI1 Germ cell tumor76

FP5-05STUDY OF RELATIONSHIP BETWEENPLASMACYTOID DENDRITIC CELLS ANDMINIMAL RESIDUAL DISEASE INCHILDREN WITH ACUTE LYMPHOBLASTICLEUKEMIAWenli Zhao 1 , Yi Han, Zhenghua Ji, Yihuan ChaiDepartment of Hematology, Children’s Hospital of Soochow University,Suzhou, 215003, ChinaOBJECTIVE: To explore the relationship betweendendritic cells (DCs) and minimal residual disease(MRD) in children with pre-B acute lymphoblasticleukemia (Pre-B ALL), myeloid DCs (MDC) andPlasmacytoid DCs (PDC) from peripheral blood(PB) or bone marrow(BM) of pediatric patientswith ALL before or after remission were analyzed.METHODS: Expressions of CD11c (MDC) andCD123(PDC) from peripheral blood or bonemarrow of pediatric patients with Pre-B ALL atdiagnosis were evaluated by four color cytometry.These markers were tested again at the thirty-thirddays after application of CCLG-2008 protocol. 2)MRD was monitored with six groups of monoclonalantibodies by four color cytometry.RESULTS: Percentages of CD11c and CD123 were0.0125±0.00007 and CD123 0.0259±0.00065respectively from PB (n=29), 0.0171±0.00016 andCD123 0.079±0.01490 from BM (n=29) at diagnosis.They were 0.0318±0.06961 and 0.0773±0.03836respectively from PB, 0.0318±0.00612 and0.1566±0.14733 (n=14) from BM at the thirty-thirddays of therapy. Five control numbers were0.1387±0.00233 and 0.0882±0.00029 respectivelyfrom PB. 2 ) MRD values were variance from2.78x10 -1 to 1yr (chronic ITP) andwhose symptoms were not easily controlled with medical therapy. Agood response was defined as an increase in the platelet count of >50,000/mm 3 off therapy. A poor response was defined as an increase inthe platelet count of < 50,000/mm 3 off therapy. Acute ITP meant theplatelet count returned to normal (> 150,000/mm 3 ) within 6 monthsafter diagnosis, and relapse did not occur. Chronic ITP meantpersistence of acute ITP for > 6 months. Recurrent ITP meant theplatelet count decreased to

FP6-01THE EXPRESSION AND SIGNIFICANCE OFLINGO-1 IN BRAIN TISSUE OF NEWBORNWMD RATSJuan CHEN, Xiaoyong WANG, Yujia YAO, YongxiuCHEN, Man XIONG, Yi YANG, Chao CHENDepartment of Pediatrics,West China Second University Hospital, SichuanUniversity, Chengdu Sichuan 610041, ChinaFP6-02EFFICACY OF DIFFERENT PROBIOTICSSUPPLEMENT TO PREVENT NECROTIZINGENTEROCOLITIS OR DEATH: ANIMAL MODELHisao-Yu Chiu, Hsin-Yang Hsieh, Hsiang-Yu Lin, Ming-HsiaLin, Bai-Horng Su, Hung-Chih LinDivision of Neonatology, Department of Pediatrics, China Medical UniversityHospital, Taichung, TaiwanOBJECTIVE: To set up WMD model for 2d-old SDrats by ligation of right carotid artery (ischemia) andtreated with 6% oxygen and 94% nitrogen for 4 hours(hypoxia)using Back′s Method and to observeLingo-1mRNA levels of the WMD model group and theBDNF treated group. To investigate the significance ofLingo-1 in the pathogenesis of WMD and the protectiverole of BDNF for damaged brain by injecting into theWMD rats brain ventricles.METHODS: After establishment of WMD model for2d-old SD rats and injected BDNF into the rat brainventricles of WMD rats, Situ hybridization was used toassess the expression of Lingo-1mRNA in brain tissue,and the real time PCR method was applied to detect thechanges in the expression of Lingo-1mRNA at thedifferent time of HI.RESULTS: The expressions of Lingo-1mRNA in allthe parts of brain tissues of WMD were observed,especially in the cortex and hippocampal. Theexpressions of Lingo-1mRNA in WMD groups at8h,24h,48h,72h and 7d after WMD were significantlyhigher than those of the all control groups(P

FP6-03FACTORS AFFECTING THETRANSCUTANEOUS BILIRUBIN LEVELS ATONE MONTH IN FULL-TERM、BREAST-FEDINFANTSYoshitada Yamauchi 1 , Misao Kageyama 2 , MakotoNakamura 2 , Kazue Nakamura 2 ,YukoMiyashima 2 ,Junko Arimichi 3 and Katsuhiko Tada 3Dept. of Clinical Research 1 , Division of Neonatology 2 , Dept. of Obstetrics 3 ,National Hospital Organization, Okayama Medical Center, JapanOBJECTIVES: WHO/UNICEF recommends the exclusivebreastfeeding for at least 6 months after birth. However, it iswell known that incidence of phototherapy withhyperbilirubinemia increases and jaundice also continues for along period after discharge from hospital in breast-fed infants.Exclusive breastfeeding rate in our hospital (Baby-FriendlyHospital) is about 80% at one month. Some factors have yet tobe determined in regard to their influence on prolongedjaundice at one month in breast-fed infants. The purpose ofstudy was to determine whether the variables such as mother’sage, birth weight, gestational age, sex, weight loss, peak serumbilirubin, mode of delivery during the first week of life andhow weight gain after discharge from hospital affects theserum bilirubin levels in breast-fed infants at one month.METHODS: 180 healthy, full-term, breast-fed, Japaneseneonates who were born in our hospital without complicationswere used for this study. All infants were breast-fed at time ofdischarge from hospital. Factors affecting the serum bilirubinlevels in breast-fed infants at one month were evaluated. Thetotal serum bilirubin level was assessed using a transcutaneousjaundice meter (JM-103) during the first week of life and atone month.RESULTS: We found the significant correlation between peakTcB at sternum during the first week of life and TcB at onemonth in all infants (r=0.356, p

FP6-05ROLE OF RENIN-ANGIOTENSIN SYSTEM INA RAT MODEL OF NEONATAL CHRONICLUNG DISEASEChung-Ming Chen 1 , Yaw-Dong Lang 2 , Hsiu-ChuChou 3 , Leng-Fang Wang 4Department of Pediatrics, Taipei Medical University Hospital, Taiwan 1 ,Graduate Institute of Medical Sciences, Taipei Medical University, Taiwan 2 ,Department of Anatomy, Taipei Medical University, Taiwan 3 , Department ofBiochemistry, Taipei Medical University, Taiwan 4BACKGROUND: Oxygen toxicity plays animportant role in the lung injury that may lead tolung fibrosis. Angiotensin II is a profibrotic mediatorwhich induces human lung fibroblast proliferation.We investigated the effects of hyperoxia on thecomponents of renin-angiotensin system (RAS) andcollagen production and the therapeutic effect ofangiotensin II type 1 receptor (AT1R) blocker inroom air- and hyperoxia-exposed newborn rats.METHODS: Rat pups were exposed to 1 week of >95% O 2 and a further 2 weeks of 60% O 2 . AT1Rblocker treated-rats received intraperitoneal injectionof losartan 10 mg/kg/day during the first postnatalweek and 5 mg/kg/day from postnatal 2-week to3-week old.RESULTS: Hyperoxia significantly increased totalcollagen, type I collagen, and α-smooth muscle actin(α-SMA) expression when compared to roomair-exposed rats on postnatal days 7 and 21. RAScomponents including angiotensinogen,angiotensin-converting enzyme, angiotensin II, andAT1R were significantly increased by hyperoxiawhereas AT2R was not significantly different whencompared to room air-exposed rats on postnatal days7 and 21. Hyperoxia significantly increasedextracelluar signal-regulated kinase phosphorylationbut did not affect the phosphorylation levels of p38or c-Jun N-terminal kinase on postnatal days 7 and21. Losartan significantly reduced total collagen andtype I collagen and α-SMA expression whencompared to room air-exposed rats on postnatal days7 and 21.CONCLUSIONS: Hyperoxia induces lung collagenproduction via the activation of RAS in newborn ratsand losartan reduces lung collagen production. AT1Rblocker may represent a novel therapeutic strategyfor hyperoxia-induced lung fibrosis.[Keywords]Angiotensin converting enzyme, Angiotensin,Angiotensin II types 1 and 2 receptors, CollagenFP6-06IDENTIFICATION OF ARGINASE-1 ANDADENOSINE DEAMINASE INVOLVED INIMPAIRMENT OF NEONATAL INNATE ANDADAPTIVE IMMUNE RESPONSES BYPROTEOMIC DIFFERENTIAL APPROACHESHong-Ren Yu 1 , Ho-Chang Kuo 2 , Ling-Sai Chang 3 ,Chih-Chiang Wu 4 , Lin Wang 5 , Jiunn-Ming Sheen 6 ,Chia-Yu Ou 7 , Kuender D. Yang 8Department of Pediatrics, Chang Gung Memorial Hospital-Kaoshiung MedicalCenter 1 , Division of Pediatric Allergy and Immunology; Department ofPediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center; ChangGung University, Kaohsiung, Taiwan 2 , Pediatrics, Chang Gung MemorialHospital-Kaohsiung Medical Center 3 , Division of Allergy and Immunology,Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung MedicalCenter 4,5 , Pediatrics, Chang-Gung Memorial Hospital 6 , Obstetrics, Chang GungMemorial Hospital-Kaohsiung Medical Center, Taiwan 7 , TBC, Chang GungMemorial Hospital at Kaohsiung; and Chang Gung University 8) (Taiwan)BACKGROUND: Human newborns are knownsusceptible to microbial infection. This susceptibility isgenerally attributed to immaturity of the newbornimmune system. However, the mechanisms for impairedimmunity in newborn are still incompletely defined. Inthis study, we sought to elucidate impairment of neonatalinnate and adaptive immunity by comparing theproteomic differential approaches.METHODS: leukocytes from cord blood and adultperipheral blood were subjected to two-dimensionalpolyacrylamide gel electrophoresis (2D-PAGE) analysisfor identifying. Differential protein displays, followed byfunctional validation of neonatal innate and adaptiveimmunity.RESULTS: There were 34 differentially expressedproteins between cord blood MNC and adult MNCidentified by 2D-PAGE. The differentially displayedproteins were clustered into two major signal pathways,cellular processing and purine metabolism. Westernblots validated that abundant arginase-1 (ARG1) andRho GDP-dissociation inhibitor 2 (RhoGDI2) are mainlyfound in phagocytes: granulocytes and monocytes. Incontrast, less adenosine deaminase (ADA) and beta-actinlevels were found in monocytes. Functional validationconfirmed that modulation of arginine/ adenosine systemimproved neonatal phagocyte and T cell responses.CONCLUSION: Results from this study highlight thatimpaired innate and adaptive immunity in neonates maybe reversed by modulation of protein displays viaproteomic differential displays followed by functionalcorrection.[Keywords] neonate, immunity, proteomics, adenosine deaminase,arginase80

FP7-01TRANSMISSION AND CLINICAL FEATURESOF NOVEL H1N1 VIRUS INFECTIONS INHOUSEHOLD CONTACTS IN TAIWANWei-Hua Chen, MD 1 ; Hsiao-Ting Hung, MD 1 ;Min-Hsiung Lee, MD 1 ; Chun-Yi Lu, MD, PhD 1 ;Pei-Lan Shao, MD 1 ; Tsui-Yen Fang, RN 1 ; Luan-YinChang, MD, PhD 1 ; Li-Min Huang, MD, PHD 11 Section of Infectious Diseases, Department of Pediatrics, National TaiwanUniversity Hospital, Taipei, TaiwanFP7-02Correlation of Viral Load to Severity and ProlongedVirus Shedding Time to Age in Novel H1N1InfectionsChung-Chen Li, Lin Wang, Ling-Sai Chang, Kuo-ShuTang, Ying-Jui Lin, Hsuan-Chang Kuo, Kuender D. YangDepartments of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung MedicalCenter, Kaohsiung, TaiwanOBJECTIVE : Although Novel H1N1 virus has causedpandemics associated with significant morbidity andmortality, its transmission has not been thoroughlyinvestigated. This study was designed to investigate novelH1N1 virus transmission and clinical outcomes withinhouseholds.METHODS : This is a prospective family cohort study toinvestigate patients of novel H1N1 infection in Taiwan andfamily members between August 2009 and November2009. Patients and household members underwent clinicalevaluations, virological studies and questionnaire-basedinterviews. Novel H1N1 virus infection was defined aseither positive H1N1 PCR or serum hemagglutinininhibition (HAI) titer ≥1:40. Clinical manifestations andoutcomes were also analyzed.MAIN RESULTS : Eighty-seven families including 87index cases and 222 household members were enrolled.Among index patients, the mean (SD) age was 10.1 (6.8)years old (median 9.0, range, 1.1 to 37.6 years). Theoverall novel H1N1 virus transmission rate to householdcontacts was 27% (59/222 household contacts), and theaverage intra-family reproduction number (Ro) is 0.68.The transmission rates were 58% (35/60) for siblings, 0%(0/1) for cousins, 14% (19/138) for parents, 22% (4/18) forgrandparents, and 20% (1/5) for uncles and aunts,respectively (p

FP7-03SUCCESSFUL PREDICTION OF SEASONALINFLUENZA EPIDEMIC STRAINS THROUGHEARLY SURVEY OF SEROPROTECTIONRATE IN CHILDREN IN TAIWANWei-Ju Su, 1,2 Pei-Lan Shao, 2 Ming-Tsan Liu, 1Ding-Ping Liu, 1 Kuo-Chin Huang 3 , Luan-YinChang, 2 Chun-Yi Lu, 2 Jen-Ren Wang, 4 Hsin-RuShih, 5 Daniel Tsung-Ning Huang, 6 Shin Chi, 6Li-Min Huang 21 Centers for Disease Control, Taiwan; Departments of Pediatrics 2 andFamily Medicine 3 , National Taiwan University Hospital; 4 Natioanl ChengKung University; 5 Chang Gung University; 6 Department of Pediatrics,Mackay Memorial Hospital (Taiwan)BACKGROUND: Many vaccine-like strains circulated inTaiwan at least 1 to 2 years before being recommended asvaccine strains by the WHO. We wanted to discover theserological signals which indicated the possible dominantlycirculating subtype in the coming influenza winter seasons.METHODS: In Taiwan, the winter season was generallyrecognized from December to February. Healthy children aged6 months-5 years, adults aged 18-60 years, and elderly aged>60 years living in Taipei City and Taipei County wererecruited to receive seasonal trivalent inactivated influenzavaccination from October to December during 2006/2007 to2008/2009 seasons. Serum pairs were collected at baseline and3 weeks post-immunization. Influenza local strains circulatingearly in October were provided by the laboratory-surveillancenetwork coordinated by Taiwan CDC. Using ahemagglutination inhibition (HAI) assay, we measuredantibody responses to three subtypes of influenza local strainsin stored serum pairs.RESULTS: A total of 1079 subjects of three age strata wereenrolled and HAI antibody response after seasonal influenzavaccination met the criteria of sero-protection rate set up bythe Europe's Committee for Medicinal Products for HumanUse. Among them, 301 subjects were randomly assigned to betested for local strains, which included 80, 120, and 101subjects in 06/07, 07/08, and 08/09 seasons, respectively. Thelaboratory-based surveillance network indicated thatB/Malaysia/2506/2004-like in 06/07 season,A/Brisbane/59/2007-like virus (H1N1) in 07/08 season, andA/Brisbane/59/2007-like virus (H1N1) in 08/09 season werethe dominant winter influenza strains in Taiwan. The lowestproportion of subjects with HAI titer ≥ 40 at baseline wasobserved in children against the B/Taiwan/0050/2006 in 06/07season, A/Taiwan/785/2006 (H1N1) in 07/08 season, andA/Taiwan/951/2007 (H1N1) in 08/09 season, which correlatedwell with the circulating influenza subtype in the followingwinter peak seasons.CONCLUSION: Low seroprotection rate in children againsta specific locally circulating strain predicted the dominantlycirculating subtype of influenza virus in the coming winterseason. A year-end pre-seasonal serology survey may bewarranted to identify the possible circulating strain and tailorthe disease-control strategy accordingly.FP7-04PREVALENCE OF DRUG-RESISTANT VIRUSESAND VIRUS-SHEDDING PERIOD IN PEDIATRICINFLUENZA PATIENTS TREATED WITHOSELTAMIVIR OR ZANAMIVIRDaisuke Tamura, M.D., 1 Norio Sugaya, M.D., 2 MasatakaIchikawa, M.D., 3 Masahiko Yamazaki, M.D., 4 ChiharuKawakami, 5 Hideaki Shimizu, 6 Ritei Uehara, M.D., Ph.D., 7Maki Kiso, D.V.M., Ph.D., 1 Eiryo Kawakami, M.D., 1 KeikoMitamura, M.D., 8 and Yoshihiro Kawaoka, D.V.M.,Ph.D. 1,9,10,111 Division of Virology, Department of Microbiology and Immunology, Institute ofMedical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan;2 Department of Pediatrics, Keiyu Hospital, Kanagawa, Japan; 3 Department ofPediatrics, Ichikawa Children’s Clinic, Kanagawa, Japan; 4 Department ofPediatrics, Zama Children’s Clinic, Kanagawa, Japan; 5 Yokohama City Instituteof Public Health, Kanagawa, Japan; 6 Kawasaki City Institute of Public Health,Kanagawa, Japan; 7 Department of Public Health, Jichi Medical University,Tochigi, Japan; 8 Department of Pediatrics, Eiju General Hospital, Tokyo, Japan;9 ERATO Infection-Induced Host Responses Project, Japan Science andTechnology Agency, Saitama, Japan; 10 International Research Center forInfectious Diseases, Institute of Medical Science, University of Tokyo,Shirokanedai, Minato-ku, Tokyo, Japan; 11 Department of PathobiologicalSciences, University of Wisconsin, Madison, WI, USA.OBJECTIVES: Although reports of influenza viruses resistantto a neuraminidase inhibitor zanamivir are much less thanthose of another neuraminidase inhibitor oseltamivir-resistantclinical isolates, it is unknown whether this is due to thelimited use of zanamivir or a property of the drug. To comparethe prevalence of drug-resistant viruses and virus-sheddingperiod in seasonal influenza virus-infected children treatedwith either oseltamivir or zanamivir.METHODS: Clinical specimens (throat or nasal swab) werecollected from a total of 144 pediatric influenza patients duringthe 2005-2006, 2006-2007, 2007-2008, and 2008-2009influenza seasons. Neuraminidase inhibitor-resistant mutantswere detected among the isolated viruses by sequencing theviral hemagglutinin and neuraminidase genes. Sensitivity ofthe viruses to neuraminidase inhibitors was tested by sialidaseinhibition assay.MAIN RESULTS: In oseltamivir- or zanamivir-treatedinfluenza patients who were statistically comparable in theirage distribution, vaccination history, and type or subtype ofvirus isolates, the virus-shedding period in zanamivir-treatedpatients was significantly shorter than that inoseltamivir-treated patients. Further, the prevalence ofzanamivir-resistant viruses was significantly lower than that ofoseltamivir-resistant viruses.CONCLUSION: In comparison to treatment with oseltamivir,treatment of pediatric patients with zanamivir resulted in theemergence of fewer drug-resistant influenza viruses and ashorter virus-shedding period. We conclude that zanamivirshows promise as a better therapy for pediatric influenzapatients.[Keywords] Influenza virus, neuraminidase inhibitor, Oseltamivir,Zanamivir[Keywords] prediction, epidemic strains, influenza, children,haemagglutinin inhibition titers82

FP7-05THE INCIDENCE AND PROGNOSIS OFCONGENITAL CYTOMEGALOVIRUS INFECTIONIN JAPAN AND VIETNAMMasami Miyakawa 1 , Michiko Doi 1 , Hideki Motomura 1 ,Masako Moriuchi 1 ,Hiroshi Yoshino 2 , LayMyint Yoshida 2 ,Koya Ariyoshi 2 , Le H. Tho 3 , Dang Duc Anh 4 , Naoki Inoue 5 ,Hiroyuki, Moriuchi 11 Dept of Mol Microbiol Immunol, Grad Sch of Biomed Sci, NagasakiUniversity; 2 Dept of Clin Med, Inst of Trop Med, Nagasaki University;3 Khanh Hoa Provincial Public Health Service, Vietnam; 4 National Instituteof Hygiene and Epidemiology, Vietnam; 5 National Institute of InfectiousDiseases, Japan.Congenital cytomegalovirus (CMV) infection leads to variousclinical manifestations and outcomes, thus the influence on thepublic health and socioeconomic burden can be significant. Itsepidemiological features are diversified by environmental andsocioeconomic factors. It has been recognized as one of the mostimportant congenital infections and a leading cause of congenitalcentral nervous system disorders in developed countries; however,its epidemiological and clinical characteristics in Asian countriesremain obscure.We have been conducting congenital CMV infectionmass-screening projects in Japan and Vietnam, two Asiancountries that differ in environmental and socioeconomic features.In Japan, a pilot study aimed for the establishment of a nationaluniversal screening of neonates for congenital CMV infection hasbeen conducted in 6 prefectures including Nagasaki where CMVseroprevalence in pregnant women was 87.5%. Urine sampleshave been collected in filter paper during the first week after birth,and subjected to real-time PCR for CMV-DNA. A total of 2862samples have been tested in Nagasaki as of January 5 in 2010, and8 infants (0.28%) were positive. One infant presented withhydrocephalus, intrauterine growth retardation, sensorineuralhearing loss and thrombocytopenia at birth and his psychomotordevelopment has been moderately delayed as of 10 months of age.Another infant was asymptomatic at birth, but developed Westsyndrome at 7 months of age. Other 6 infants have beenasymptomatic, although mild liver dysfunction has beendemonstrated in two and transient neutropenia was observed inone infant.In Nha Trang, Vietnam, a birth cohort study is in progress: a totalof 2000 infants born at Khanh Hoa General Hospital are to bescreened for several congenital pathogens including CMV.Precedently, we conducted a pilot study in this area in 2007, andinvestigated 222 pairs of maternal and cord specimens for theprevalence of CMV infection. We have demonstrated andpresented in the previous congress that maternal seroprevalencewas 100%, and two infants (0.9%) were CMV-DNA positive.CMV-IgG avidity rates of their mothers were high (68% and69%), suggesting reinfection. Those two infants had negativeCMV-IgM and were asymptomatic at birth; however, a detailedfollow-up study wasn’t conducted.FP7-06INTRODUCTION OF A SINGLE AMINO ACIDMUTATION IN ENTEROVIRUS 71 2B PROTEINRESULTS IN DEFECTIVE VIRALREPLICATION –A NEW PARADIGM OF HOSTCELL APOPTOSIS MODULATION BY A VIRUSChun-Yi Lu, Hsiu-Ming Shih*, Wei-ting Liu, Yi-Ting Tsai,Luan-Yin Chang, Li-Min HuangDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan;*Institute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanOBJECTIVE: Enterovirus 71 (EV71) is one of the mostimportant viruses causing central nervous system infections inchildren in the post-polio era. The 2B protein of enterovirusesis highly conserved in evolution, suggesting its important rolein enterovirus replication. The current study was aimed todisclose the roles of 2B in EV71 replication.METHODS: The 2B sequences of various enterovirusesincluding EV71 were analyzed. Protein-protein interactionswere determined by co-immunoprecipitation. By using reversegenetic technologies, infectious cDNA clones of EV71 wereestablished. Infectious clones with various 2B mutants werecreated by site-directed mutagenesis. The production ofwild-type EV71 and various mutants were determined byimmunofluorescence assay. Cellular apoptosis was assayed byusing Annexin V staining determined with flowcytometry.RESULTS: A reversed Bcl-2 homology domain 3 (BH3)-likesequence over the N-terminus of EV71 2B was identified.Co-immunoprecipitation experiments confirmed 2B competeswith MULE, a Mcl-1 E3 ligase, in Mcl-1 binding. Severalamino acids in the BH3-like domain of 2B were determined tobe the interacting points. Binding of 2B at Mcl-1 BH3 domainresulted in decreased Mcl-1 ubiquitination and degradation.The host cell apoptosis was in turn increased. In the infectiousclone system, introducing a single amino acid atMcl-1-interacting points at 2B was sufficient to reduce thevirus production in cell cultures. Introducing of multiple aminoacid mutations in this area makes the virus totally unable toreproduce in cells. Over-expression of EV71 2B rescued thereplication-defective viruses.CONCLUSIONS: Our study provides a new paradigm bywhich a virus modulates host cell apoptosis. Stabilization ofMcl-1 by EV71 2B prevents host cells from early apoptosisand provides sufficient time for EV71 replication. Targeting2B-Mlc-1 binding is a potential novel therapeutic strategy. Inaddition, the 2B-mutated and hence replication-defectivemutant viruses are potential vaccine candidates.[Keywords] Enterovirus 71, 2B, replication, ubiquitinationIn this congress, we will present interim reports of the twoongoing studies in Japan and Vietnam and discuss possibleimpacts of congenital CMV infection on these two Asiancountries. We thank K. Fujieda and others (Congenital CMVInfection Study Group) and obstetric staffs in both countries whocollected neonatal samples.[Keywords]Congenital Cytomegalovirus infection, Japan and Vietnam,mass-screening program, real-time PCR, prognosis83

FP7-07CAN BOVINE LACTOFERRIN-CONTAININGPRODUCTS PROTECT CHILDREN FROMNOROVIRUS OUTBREAK?Hiroyuki Moriuchi , Masanori Egashira, MasakoMoriuchiDepartment of Pediatrics, Nagasaki University Hospital, Nagasaki, Japan;Department of Molecular Microbiology and Immunology, NagasakiUniversity Graduate School of Biomedical Sciences, Nagasaki, Japan.BACKGROUND: Norovirus is an important cause ofacute gastroenteritis worldwide, and its outbreaks amonginstitutionalized adults or children have accumulated in thepast years. Nevertheless, no specific preventive ortherapeutic agent has been available yet. Lactoferrin (LF),a milk-derived glycoprotein with a number of biologicalactivities, has recently been reported to have anti-noroviruseffect in vitro. We have recently reported that daily intakeof bovine LF (bLF) reduced the severity of rotavirusgastroenteritis in children; however, its effect on norovirusgastroenteritis remains unknown.OBJECTIVE: To investigate if bLF could protect healthychildren against norovirus gastroenteritis.DESIGN/METHODS: Healthy children (less than 5 yearsold) attending day-care centers (DCC) were randomlydivided into two groups: L group assigned to take 400 mgof bLF daily for 16 weeks and N group assigned not totake LF-containing products. Guardians were asked torecord clinical symptoms and signs on a daily basis duringthe study period. Feces were collected from all childrenwith acute gastroenteritis, and tested for rotavirus withimmunochromatographic assays (ICA) and norovirus withICA and real-time RT-PCR.RESULTS: A total of 91 children (46 in L group and 45 inN group) were analyzed for the incidence of gastroenteritiscaused by rotavirus or norovirus. Two in L group and nonein N group developed mild rotavirus gastroenteritis duringthe study period. Based on ICA, 2 (4.3%) in L group and 7(15.6%) in N group developed norovirus gastroenteritis (p< 0.01). Norovirus real-time RT-PCR revealed 2 patients(4.3%) in L group and 9 (20%) in N group, consisting of 5in GI genotype and 6 in GII genotype.CONCLUSIONS: Daily intake of bLF products reducedthe incidence of norovirus gastroenteritis in healthychildren attending DCC. Taken together with our previousstudy, LF appears to protect healthy children from viralgastroenteritis. Real-time RT-PCR had better sensitivitythan ICA, and was capable of genotyping.[Keywords] norovirus, gastroenteritis, lactoferrin, day care centerFP8-01HERG GENE MUTATIONS ORPOLYMORPHISMS IN PATIENTS WITHREPAIRED TETRALOGY OF FALLOT: APOTENTIAL RISK FOR VENTRICULARARRHYTHMIASShuenn-Nan Chiu, M.D 1 , Ming-Tai Lin, M.D 1 , Mei-HwanWu, M.D, PhD, FHRS 1 , Chien-Chih Chang, M.D 1 ,Hue-Wen Hsu, M.D 1 , Jou-Kou Wang, M.D, PhD 1 ,Chun-An Chen, M.D 1 , Ching-Tsuen Shen, M.D, PhD 2 ,Olivier Thériault, PhD 3 , Mohamed Chahine, PhD 31 Department of Pediatrics, National Taiwan University Hospital and College ofMedicine, National Taiwan University, Taipei, Taiwan; 2 Department ofPediatrics, Cathay General Hospital, Taipei, Taiwan; 3 Hôpital Laval, ResearchCentre, Sainte-Foy, Quebec, Canada, G1V 4G5, and Department of Medicine,Université Laval, Quebec City, Quebec, Canada, G1K 7P4BACKGROUND: hERG gene mutations/polymorphisms areassociated with congenital and acquired long QT syndrome.However, the effects of these changes on the repolarizationabnormality, secondary to complete right bundle branch block,in repaired Tetralogy of Fallot (TOF) patients are stillunknown. This study sought to define the role of hERG genemutations in ventricular arrhythmias in these patients.METHODS AND RESULTS: We analyzed the mutations orsingle nucleotide polymorphisms (SNPs) in all exons of thehERG gene in 83 patients with repaired TOF and completedhemodynamic and electrocardiographic data. Additionally, invitro biophysical characterization of mutant alleles wasperformed using whole-cell voltage clamp after expression inXenopus oocytes. Two novel mutations (p.M645R and p.R92C,one in each) and one non-synonymous SNP (p.K897T, threepatients) were found in five (6.0%) patients. Life-threateningevents occurred in six patients and were more common in thosewith genetic variants (2/5 vs. 4/78, p=0.040). The patient withp.M645R mutation experienced cardiac arrest two years aftercardiac repair. One patient with p.K897T SNP died suddenly35 years after cardiac repair. Expression of the p.M645Rmutant allele alone in Xenopus oocytes resulted in no currentgeneration while co-expression of the mutant and wild-typealleles showed a net decrease in I Kr .CONCLUSION: In patients with TOF, the coexisting hERGmutations and non-synonymous SNP might have additiveeffects on the repolarization abnormality from right bundlebranch block after cardiac repair and may potentially increasethe risks of ventricular arrhythmias in repaired TOF patients.[Keywords]hERG gene, mutation, Tetralogy of Fallot, ventriculararrhythmia, complete right bundle branch block84

FP8-02LONG-TERM FOLLOW-UP OF TETRALOGYOF FALLOT AFTER REPAIR AT OLDER AGEMing-Chun Yang, Shuenn-Nan Chiu, Chun-An Chen,Ming-Tai Lin, Chun-Wei Lu, Jou-Kou Wang,Mei-Hwan WuNational Taiwan University Children’s Hospital, National TaiwanUniversity, Taipei, TaiwanOBJECTIVE: Patients with Tetralogy of Fallot (TOF)usually undergo total repair in early childhood. Few studieshave focused on long-term results of surgery at older age.The aim of this study is to evaluate the long-term surgicaloutcome in patients receiving total correction in latechildhood, adolescence or even adulthood.METHODS: Between 1970 and 2009, 179 TOF patients(56% male) received total correction at age older than 10years. Among them 55 (31%) of them were older than 20year-old. The mean age at diagnosis of TOF was 16.2 ± 8.4years, and the mean age at total correction was 19.2 ± 8.3years (range 10 to 49 years). We reviewed the medicalrecords and telephone interviewed the patients for thecurrent status.MAIN RESULTS: The most common preoperativesymptom was exertional intolerance (93.7%). 82.4%patients were in NYHA functional class II or III.Preoperatively, significant ventricular arrhythmia occurredin 4.0% of patients, and the incidence increases with age ofsurgery (19.0% in those older than 30 years-old). Majormorbidity before cardiac repair includes infectiveendocarditis (12 patients, 6.8%) and brain abscess (9patients, 5.1%). Thirty of 179 patients received shuntsurgery first at the mean age of 10.5 ± 6.2 years, and 2 ofthem developed pulmonary hypertension after shuntoperation. Right ventricular outlet reconstruction wasperformed by transannular patch (37.4%), right ventricularoutlet tract patch (38.0%), infundibular muscle resection(22.8%), and Rastelli type operation (1.8%). Follow-upperiod ranges from 1 month to 35 years. The 10-, 20- and30-year survival rate was 96.5%, 93.2% and 89.9%,respectively. Early mortality occurred in 4 patients (2.2%).Freedom of ventricular arrhythmia 30 years after operationwas 84.1%, which can be predicted by QRS durationlonger than 160ms. Residual moderate to severepulmonary regurgitation (PR) was found in 15.2% ofpatients. By means of multivariate analysis, length of ICUstay was the only significant negative predictor of latecardiovascular mortality.CONCLUSION: If left without total repair, TOF patientsolder than 10 year-old are nearly always symptomatic withsignificant morbidities. Surgical outcome are comparableto those repaired early, including survival and risk ofventricular arrhythmia.FP8-03SYSTEMATIC REVIEW AND META-ANALYSISOF PULMONARY VALVE REPLACEMENT INCHILDREN AND ADULTS AFTER SURGICALREPAIR OF TETRALOGY OF FALLOTYIU-FAI CHEUNG, MD , Eddie WY Cheung, MBBS,Wilfred HS Wong, MMedScDepartment of Paediatrics and Adolescent Medicine, Queen Mary Hospital, TheUniversity of Hong Kong, Hong Kong, ChinaOBJECTIVES: Reported outcomes of surgical PVR inchildren and adults after TOF repair were based onrelatively small observational studies. This systematicreview and meta-analysis aimed to determine theoutcomes and impact on right ventricular (RV) functionof surgical pulmonary valve replacement (PVR) inpatients after repair of tetralogy of Fallot (TOF).METHODS: The PubMed database was searched fromits inception to April 2009. Observational studiesreporting on the following outcomes measures aftersurgical PVR were reviewed: early and late all-causemortalities, redo-PVR rate, and changes in indexed RVvolumes, ejection fraction (EF), and QRS duration afterPVR.RESULTS: Of the 305 citations screened, 15 met thecriteria and were analyzed. Pooled early mortality(n=595) was 2.1% (95% CI, 1.1 to 4.0%). Late mortalityrate was 0.5%/patient-year (95% CI, 0.2 to0.8%/patient-year) and redo-PVR rate was1.9%/patient-year (95% CI, 1.3 to 2.5%/patient-year).Data on RV volumes and ejection fractions wereavailable from 5 studies (n=141). Pooled meandifferences of indexed RV end-diastolic and end-systolicvolumes were -64ml/m 2 (95% CI, -55 to -72ml/m 2 ) and-37ml/m 2 (95% CI, -30 to -45ml/m 2 ), respectively. Nosignificant changes in pooled mean difference of RV EF(95% CI, -3 to 1%) and QRS duration (95%CI, -1 to12ms) were observed.CONCLUSIONS: Surgical PVR in patients after TOFrepair is associated with low early and late mortalitiesand significant decrease in RV volumes, but with nochanges in RV EF or QRS duration.[Keywords]Meta-Analysis, Pulmonary Valve Replacement, Tetralogy of Fallot[Keywords] Tetralogy of Fallot, late repair, outcome85

FP8-04IMPLICATIONS OF RESTRICTIVE RIGHTVENTRICULAR PHYSIOLOGY IN RIGHTVENTRICULAR ADAPTATION TO CHRONICPULMONARY REGURGITATION IN PATIENTSWITH REPAIRED TETRALOGY OF FALLOTChun-An Chen1,2, Jou-Kou Wang1, Wen-Yih Tseng3,4,Chung-I Chang5, Ing-Sh Chiu5, Yih-Sharng Chen5,Chun-Wei Lu1,6, Ming-Tai Lin1, Hsin-Hui Chiu1, Mei-HwanWu1Department of Pediatrics, National Taiwan University Hospital, Taipei,Taiwan, 2Heart Failure Center, National Taiwan University Hospital,Taipei, Taiwan, 3Center for Optoelectronic Biomedicine, College ofMedicine, National Taiwan University, Taipei, Taiwan, 4Department ofMedical Imaging, National Taiwan University Hospital, Taipei, Taiwan,5Department of Surgery, National Taiwan University Hospital, Taipei,Taiwan, and 6Adult Congenital Heart Center, National Taiwan UniversityHospital, Taipei, TaiwanOBJECTIVE: To explore the relationship of restrictive rightventricular (RV) physiology (antegrade pulmonary arterialflow in late diastole) with RV adaptation to pulmonaryregurgitation (PR) in repaired tetralogy of Fallot (rTOF).METHODS: We studied 80 consecutive rTOF patients (age22.7 ± 7.8 years) without significant residual pulmonarystenosis using cardiovascular magnetic resonance and tissueDoppler imaging. Restrictive RV physiology was assessed byDoppler echocardiography. Surgical methods used for rightventricular outflow tract (RVOT) reconstruction and otherrelevant clinical data were extracted from medical records.RESULTS: Restrictive RV physiology was observed in 40%of study patients. Patients with restrictive RV physiology hadsignificantly lower PR fraction, RV end-diastolic volumeindex (RVEDVi), myocardial performance index, higher latediastolic annular velocity, less RVOT aneurysm andtransannular patch (TAP) than those without. Age at repair(odds ratio: 0.61, P = 0.042), the use of TAP (odds ratio: 0.20,P = 0.031), RVEDVi (odds ratio: 0.93, P = 0.001), andmyocardial performance index (odds ratio: 0.001, P = 0.027)were independently associated with restrictive RV physiologyon multivariate analysis. Furthermore, PR fraction correlatednegatively with RV ejection fraction in patients withoutrestrictive RV physiology, whereas such relationship wasabsent in those with restrictive RV physiology, either inoverall patients or those with significant PR (PR fraction >20%, 55 patients). Subgroup analysis in patients withsignificant PR showed smaller RVEDVi (111.7 ± 14.8 versus139.2 ± 34.2 ml/m2, P < 0.001) and better RV ejectionfraction (51.2 ± 5.5 versus 46.8 ± 9.2 %, P = 0.042) in patientswith restrictive RV physiology (13 patients) than thosewithout in the presence of similar PR fraction between thesetwo groups.CONCLUSION: Restrictive RV physiology was prevalent inrTOF whose predominant hemodynamic residual wasPR-induced RV volume overload. It was associated withyounger age at repair, better RV function, less RVOTaneurysm, and less use of TAP during RVOT reconstruction.Uncoupling of PR to RV function in patients with restrictiveRV physiology suggested that this phenomenon might serve asa marker for better RV adaption to chronic PR.FP8-05CARDIAC RELATED TBX1 AND TBX20 GENEEXPRESSION ARE DOWN-REGULATEDDURING EMBRYONIC CARDIACDEVELOPMENT IN RETINALDEHYDROGENASE TYPE 2 GENEKNOCK-DOWN ZEBRAFISHJia Hou 1 , Hao Yong Gui 2Cardiovascular center, Children's Hospital of Fudan University 1 , CardiovascularCenter, Children's Hospital of Fudan University, Shanghai 2 (China)OBJECTIVES: To establish a model of retinal dehydrogenase type 2(raldh2) gene knock-down zebrafish embryos, and to explore the effect ofinsufficient retinoid acid (RA) signaling on the early embryonic cardiacdevelopment, especially on the regulation of cardiac relatedtranscriptional factors tbx1 and tbx20 expression..METHODS: We designed morpholino antisenseoligonucleotides (MO) targeting zebrafish raldh2 gene toknock-down its expression and constructed raldh2-EGFPplasmid to verify the effectiveness and specificity ofraldh2-MO. The embryonic cardiac phenotype and cardiacfunction were analyzed and compared between wild-type andraldh2-MO group. Then, we described the expression patternof tbx1 and tbx20 gene in zebrafish embryos, and the regulationof their expression when raldh2 gene was knocked down toelucidate the underlying mechanism of RA signaling in thecardiac development.RESULTS: Raldh2-MO microinjection could effectivelyknock-down raldh2 gene expression, the mortality andabnormal embryo rate rose with the increase of raldh2-MOdosage. Raldh2-MO embryos exhibit abnormal cardiacphenotype, including swollen pericardial cavity, tubular heart,incomplete D-loop, abnormal atria and ventricle development,blood regurgitation, slow blood flow and weak heart beat. Theresults of whole-mount in situ hybridization of tbx1 and tbx20probes revealed that these genes had distinct expressionpatterns, tbx1 expressed in cardiac outflow tract, otic vesicleand pharyngeal arch, while tbx20 expressed in cardiac outflowtract and atrium, branchio motor neuron, tegmentum and retinabut both of them expressed in the embryonic heart. In raldh2knock-down embryos, tbx1 and tbx20 expression weredown-regulated in the heart to some extent.CONCLUSIONS: The RA deficiency zebrafish embryo modelcan be effectively established by raldh2-MO microinjection.RA signaling plays a critical role in several key stages ofcardiac development and may interact with cardiac relatedtranscriptional factors to regulate cardiogenesis anddevelopment. The expression of tbx1 and tbx20, which playimportant roles during embryogenesis, can be regulated by RAsignaling during cardiac development, and the underlyingmechanism still needs further investigation.[Keywords]retinal dehydrogenase type 2, retinoid acid, cardiacdevelopment, tbx1, tbx20, zebrafish[Keywords]Tetralogy of Fallot; Restrictive right ventricular physiology;Pulmonary regurgitation; Tissue Doppler imaging; Cardiac magneticresonance86

FP8-06THE ASSOCIATION BETWEENHYPOPLASTIC LEFT HEART SYNDROMEWITH CONGENITALTHROMBOCYTOPENIA AND JACOBSENSYNDROMEAkifumi Toyoda, Hiroki Nagamine, Nobutaka Shimizu,Hiroshi Ono, Yoshihiro Nakamura, Tatsuo Katori,,Takashi IgarashiDepartment of Pediatrics, Graduate School of Medicine and Faculty ofMedicine, University of Tokyo, Tokyo, JapanBACKGROUND: Jacobsen syndrome (JS) is a very raredisorder (1/100,000 birth), caused by segmentalmonosomy for the distal end of the long arm ofchromosome 11 with variable phenotypic expressivity. JSis frequently accompanied by congenital thrombocytopeniaand congenital heart disease, notably hypoplastic left heartsyndrome (HLHS). However, the evaluation for the casesof HLHS that are complicated by congenitalthrombocytopenia, has not been reported previously.AIMS: To assess the association between HLHS withthrombocytopenia and JS.SUBJECTS & METHODS: We retrospectively studiedtwenty-seven patients with HLHS, who were admitted toour institution at neonatal period between December 2001and December 2008. Thrombocytopenia is defined as theplatelet count under 100,000 per microliter at birth.RESULTS: Six of twenty-seven HLHS patients (22%;five females) were associated with the presence ofthrombocytopenia at birth. One patient was thought thatsome infection resulted in DIC. The other five patientswere thought idiopathic thrombocytopenia, because therewere not existed the cause of platelet depletion, such asinfection, clotting problems, DIC, and so on. The plateletcount decreased 22,000 to 89,000 (mean ± SD is 48,000 ±24,000) per microliter. To avoid the risk of uncontrolledbleeding, all patients were given the platelet transfusionduring their operation. As a result, all patients did notexperience bleeding. Four of five patients with idiopathicthrombocytopenia were tested for chromosomal study, andall were established an accurate diagnosis of partialdeletion of the long arm of chromosome 11. And thesepatients presented with the symptoms of JS, including:characteristic facial dysmorphism (skull deformities,hypertelorism, ptosis, short nose, etc), ophthalmic disorder,urogenital abnormality, mental retardation, and all that.CONCLUSIONS: HLHS patients with thrombocytopeniamay be relatively common, and these patients arerecommended chromosomal study because of suspectedJS.FP9-01IN UTERO AND CHILDHOOD GROWTH ANDRESPIRATORY ILLNESS IN PRESCHOOLCHILDRENYoolwon Jeong 1 , Jungwon Min 1 , Eun Ae Park 2 , YoungjooKim 3 , Hwa Young Lee 4 , Jinhwa Lee 5 , Se Young Oh 6 ,Kyunghee Jungchoi 1 , Eunhee HA 1 , Hyesook Park 1Ewha Woman University, School of Medicine. Department of PreventiveMedicine 1 , Ewha Woman University, School of Medicine. Department ofPediatrics 2 , Ewha Woman University, School of Medicine. Department ofObstetrics and Gynecology 3 , Ewha Woman University, School of Medicine.Department of Anatomy 4 , Ewha Woman University, School of Medicine.Department of Internal Medicine 5 , Kyunghee University, College of Humanecology, Department of Food and Nutrition 6 (Korea)OBJECTIVES: Chronic respiratory illness is common in youngchildren with high socioeconomic burden and increasingprevalence worldwide. Although childhood obesity and low birthweight is suggested to play a role in the development of chronicrespiratory illness, previous studies showed contradictory results. Itis also suggested that relatively lower birth weight and subsequentoverweight status in childhood increases the risk of later chronicdiseases. The purpose of this study was to examine the associationsof obesity and birth weight with chronic respiratory illness andidentify possible interaction underlying its mechanism.METHODS: The study was carried out with 422 children whowere enrolled in a hospital-based birth cohort. Birth relatedanthropometric data were collected at birth. At age 3 years,information on the children’s respiratory illness was collectedbased on the validated core questionnaire for wheezing and asthmafrom the International Study of Asthma and Allergies in Childhood(ISAAC). Physical examination was also carried out to measuretheir weight and height. Chronic respiratory illness was defined asbeing diagnosed with a chronic respiratory disease or sufferingfrom respiratory symptoms for more than 3 months. Asthma wasdefined as being diagnosed with asthma or taking anti-asthmaticmedications. Wheezing was defined as having more than oneattack of wheeze and frequent cough was defined as sufferingcough occurring outside colds.MAIN RESULTS: Children with higher current weight or lowerbirth weight were at an increased risk of chronic respiratory illness.In addition, children who were initially in the lowest birth weighttertile but now belong in the highest weight tertile had more than16 times higher risk of chronic respiratory illness compared tothose who had remained in the middle tertile (p=0.01). The effectof current weight on chronic respiratory illness in children wasmodified by birth weight in an additive manner.CONCLUSION: Measures of obesity, birth weight, and itschanging trajectory can be useful in pediatric settings to betteridentify children who might be at an increased risk for suchrespiratory illness. As weight can be monitored and controlled, itcan also be incorporated into personal health care to help preventand manage chronic respiratory illness.[Keywords] growth, weight, obesity birth weight, chronic respiratory illness,interaction[Keywords]Jacobsen syndrome, hypoplastic left heart syndrome,thrombocytopenia87

FP9-02FLEXIBLE ENDOSCOPIC PLACEMENT OFTRACHEOBROCHIAL METALLIC STENT INCHILDREN —12 YEARS EXPERIENCEPei-Chen Tsao, *Wen-Jue Soong, Yu-Sheng Lee,Chia-Feng Yang, Yu-Yun Peng, Mei-Jy Jeng, Ren-BinTangDepartment of pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan;Institute of Emergency and Critical Care Medicine, National Yang-MingUniversity, Taipei, TaiwanFP9-03COMPARISON BETWEEN CO 2 AND KTP LASERSUPRAGLOTTOPLASTY IN THE TREATMENTOF SEVERE LARYNGOMALACIA IN INFANTSWen-Jue Soong, An-Suey Shiao,* Yu-Shen Lee, Pei-ChenTsao, Chia-Feng Yang, Mei-Jy Jeng, Yu-Yun Peng, Ran-BinTangDepartment of Pediatrics, Department of ENT,* Taipei Veterans GeneralHospital, Taipei, Taiwan; Institute of Emergency and Critical Care Medicine,National Yang-Ming University, Taipei, Taiwan.OBJECTIVE: Placement of tracheobronchial (TB) stentcan be challengeable in children. Here we present our 12years experience of the feasibility, efficiency and safety ofthe balloon-expandable metallic stent placement by aid offlexible endoscopy (FE) in children.METHODS: It’s a retrospective analysis study in apediatric pulmonology training center. From Jan. 1998 toDec. 2009, all consecutive patients who had intra-TB stentimplantation were enrolled. Balloon-expandable metallicstent (Palmaz or IntraStent) insertions were performed withexclusively FE only, with nasopharyngeal oxygensupplement and pinch nose ventilation under intravenoussedation in our FE room.MAIN RESULTS: In 12-year-period, 81 stents wereplaced in 51 consecutive children. Mean age was 21.4 ±24.2 month-old and body weight was 11.0 ± 5.8 kg.Among them, 35 children were severe cardiopulmonarycompromised. Stents were placed in all locations withinthe central airways: 6 (7.4%) in subglottis, 47 in (58.0%)trachea, 3 (3.7%) cross carina in tracheobronchus, and 25(30.9%, Rt10, Lt 15) in bronchus. Underlying problemswere mainly for malacia (75.3%), and stenosis (24.7%).All these patients were already under respiratory support.In 27 pts the endotracheal tube (ETT) was removed justbefore the stent deployment procedure and neverre-intubated again afterward. Multiple stents were placed,either simultaneously or sequentially, in 22 pts due toeither multiple or complicated lesions. Total proceduretime was 25.2±8.1 min. All stents were employed with nodifficulty and no complication. Seventy-nine stents(97.5%) were successfully deployed in the target sites. Twostents had migration during deployment both occurred inthe early time of study. All patients, except 2 cases withstent slipped, had immediate symptomatic improvementafter the stenting.CONCLUSION: In children, even with severecompromised cardiopulmonary status, the metallic TBstent can be accurately, safely and successfully implantedby only using FE under intravenous sedation andappropriate ventilation management, without fluoroscopyor general anesthesia. It avoids radiation exposure and is acost-saving technique.[Keywords]airway stenosis, airway malacia, balloon-expandable stent,flexible bronchoscopy, tracheobronchial stentOBJECTIVE: Traditionally, severe laryngomalacia(SLM) is surgically treated with CO 2 laser via a rigidendoscopy (RE). The potassium-titanyl-phosphate (KTP)laser also works as a thermal vaporization. It can betransmitted via a flexible fiber and pass through aflexible endoscope (FE). The study analyze and comparethe clinical variables between two interventions, the CO 2laser via RE and the KTP laser via FE, in the treatmentof the SLM. IRB approved retrospective study ofconsecutive infants with SLM treated with lasersupraglottoplasty over a 4-year period.METHODS: All enrolled infants had undergone bilaterallaser supraglottoplasty. In the early 2-year period(2006-7), infants were treated with the traditional CO 2laser technique. In the later 2-year period (2008-9),infants were treated with a new novel technique of KTPlaser via a FE under intravenous sedation withouttracheal intubation. Clinical variables were comparedbetween these two groups.MAIN RESULTS: In 4-year period, total 57 infants (27 inCO 2 group, 30 in KTP group) were enrolled. There areno statistic differences of gender, age, body weight, andduration of post laser respiratory support between thetwo groups. Clinical improvement is also comparable,85.2% in CO 2 group and 86.6% in KTP group. However,there are significant shorter durations of the waiting timeof operation, operation time, ETT use, and total hospitaldays as well as less major complications in the KTPgroup.CONCLUSION: The technique of KTP laser via FE hascomparable success to that of the CO 2 laser via RE in thesupraglottoplasty of SLM in infant. It shows moreconvenient and favorable in no need of generalanesthesia and ETT intubation, therefore, can be doneimmediately after make diagnosis that actually can savetime and medical resources.[Keywords]carbon dioxide laser, KTP laser, laryngomalacia,supraglottoplasty88

FP9-04NOTCH SIGNALING REGULATES GOBLETCELL HYPERPLASIA IN MOUSECONDUCTING AIRWAYSPo-Nien Tsao 1 , Liang-Tung Yang 2 , Ming-Fang Wu 3 ,Vesa Kaartinen 4 , Wellington V. Cardoso 51 Department of Pediatrics, National Taiwan University Hospital, Taiwan;2 Insistute of Cellular and Systems Medicine, National Health ResearchInstitutes; 3 Animal Medical Center, College of Medicine, National TaiwanUniversity; 4 Developmental Biology Program, The Saban Research Instituteof Childrens Hospital Los Angeles, Department of Pathology, Keck Schoolof Medicine, University of Southern California, Los Angeles, California;5 Pulmonary Center of Boston University School of Medicine, BostonBACKGROUND: Goblet cell hyperplasia and mucusproduction contribute to the pathogenesis of chronic lungdiseases including asthma, chronic obstructive pulmonarydisease. In the intestine Notch signaling plays opposingroles in goblet cell differentiation depending on the stageand location. Excessive goblet cell differentiation occurswhen Notch is constitutively activated in lung progenitors.Disruption of Notch signaling in the developing lungprevents formation of Clara cells, which in the adult cangive rise to goblet cells in proximal airways. However it isunclear whether Notch influences goblet celldifferentiation from Clara cells postnatally.METHODS: To address this issue, we inactivated Notchsignaling conditionally in the epithelium of trachea andproximal airway using a TGFβ3-Cre deleter mouse lineand mice carrying floxed alleles of the Pofut1 gene, whichencodes an O-fucosyltransferase essential for Notch-ligandbinding. TGFβ3-Cre targets the airway epithelium in amosaic fashion. Lung tissues were analyzed formorphology and expression of differentiation markers atvarious pre- and postnatal stages.RESULTS: The mutant mice were viable. Preliminaryanalysis of these lungs at postnatal days P8, P17 and P30revealed decreased Clara cell number and a dramaticgoblet cell hyperplasia in the proximal respiratoryepithelium. Nearly 90% of tracheal epithelium was PASand AB positive cells at P17 and P30. At P30, the gobletcell hyperplasia extended to bronchus.CONCLUSION: Our data suggest that during postnatallife Notch signaling is required to maintain conductingairway homeostasis. Notch may be required to preventgoblet cell differentiation presumably by maintaining theClara cell phenotype in proximal airways. Notch signalingmay be critical in the response of the lung toenvironmental injurants or allergens that results in gobletcell hyperplasia. Thus abnormal Notch may contribute tothe pathogenesis of asthma or chronic obstructivepulmonary disease.FP9-05OVA SUPPRESSES INDOLEAMINE 2,3-DIOXYGENASE IN DENDRITIC CELLS FROMMICE ASTHMA MODELAIZHEN LURespiratory, Children's Hospital of Fudan University, ChinaBACKGROUND: Indoleamine 2, 3-dioxygenase (IDO), atryptophan-degrading enzyme in dendritic cells (DCs),mediates an immunosuppressive effect on activated Tlymphocytes. The aim was to investigate the effect ofOVA on the expression of IDO in DCs from mice asthmamodel.METHODS: Induction of mouse asthma model by OVAsensitization and challenge. Indoleamine 2, 3 -dioxygenase expression on the level of protein andmRNA were detected by enzymeimmunohistochemistry and real time PCR,respectively.Distribution and maturation of dendriticcells were detected by immunofluorescencehistochemistry.RESULTS: (1) The manifestation and lung inflammationin model group was more serious than control group.Theconcentration of serum total IgE is 165.50±30.13ng/mlin model group, dramatically higher than control group,which is 94.45±28.30ng/ml (P

FP9-06A PROTEOMIC ANALYSIS OFCOMPLICATED PARAPNEUMONICPLEURAL EFFUSION AFTERINTRAPLEURAL FIBRINOLYTICTREATMENT IN CHILDRENJieh-Neng Wang 1 , Pao-Chi Liao 2 , Yu-Chin Tasi 3 ,Jing-Ming Wu 11 Department of Pediatrics, National Cheng Kung University Hospital,Tainan 70421, Taiwan; 2 Department of Environmental and OccupationalHealth, National Cheng Kung University Medical College, Tainan 70421,Taiwan; 3 Department of Pediatrics, Chi-Mei Medical Center, Tainan,71004, TaiwanOBJECTIVE: Although there have been many clinical reportsabout the utility of intrapleural fibrinolytic agents to improve theoutcome in both adults and children, uncertainties aboutfibrinolytic treatment remain. This study investigated theproteomic profiling data of pediatric complicated parapneumonicpleural effusion (CPE) before and after intrapleural fibrinolytictherapy obtained by two-dimensional gel electrophoresis (2D-GE)and protein identification using electrospray ionization tandemmass spectrometry (ESI-MS/MS).METHODS: Pleural effusion samples were collected from 30pediatric patients with CPE. All patients received intrapleuralurokinase treatment (urokinase 5000 IU/Kg/dose). Samplescollected before urokinase treatment were classified as the controlgroup, while those after urokinase treatment as the comparisongroup. We compared the 2D-GE images differences with computersoftware. Significant image spots were detected and identified byESI-MS/MS. Product ion scan data obtained from MS/MSexperiments were further analyzed by the protein databasesoftware.MAIN RESULTS: A total of 640 pairs of silver-stained proteinspots was observed and 76 differences (13 increased, 63decreased) were detected. Altogether, 37 significant changes to gelspots were selected for protein identification by in-gel digestion,liquid chromatography–tandem mass spectrometry and sequencedatabase search. Among these proteins, those that significantlyincreased after fibrinolytic therapy reflected the effects offibrinolytics, such as the fibrinogen gamma chain and fragmentsof fibrinogen. In those significantly decreased proteins,haptoglobin and related proteins, and alpha-1 antitrypsin andrelated proteins were observed.CONCLUSION: We concluded that intrapleural urokinasetherapy could break the fibropurulent bonds of complicatedparapneumonic effusion. The significance of the use of proteomicsanalysis of intrapleural fibrinolytic therapy in parapneumoniceffusion could gain deep insights into therapeutic mechanism andfurther prognostic factors.[Keywords]complicated parapneumonic effusion, intrapleuralfibrinolytic treatment, proteomics, protein identificationFP10-01+LONG-TERM RESULTS OF TAIWAN PEDIATRICONCOLOGY GROUP STUDIES FOR CHILDHOOD ACUTEMYELOID LEUKEMIA AND ACUTE LYMPHOBLASTICLEUKEMIADer-Cherng Liang 1 , C-P Yang 2 , D-T Lin 3 , I-J Hung 2 , K-H Lin 3 , J-SChen 4 , C-C Hsiao 5 , T-T Chang 6 , C-T Peng 7 , M-T Lin 8 , T-K Chang 9 ,T-H Jaing 2 , H-C Liu 1 , L-Y Wang 1 , T-C Yeh 1 , S-T Jou 3 , M-Y Lu 3 ,C-N Cheng 4 , J-M Sheen 5 , S-S Chiou 6 , K-H Wu 7 , G-Y Hung 10 , R-LChen 11 , S-H Chen 12 , S-N Cheng 13 ,Y-H Chang 14 , B-W Chen 15 , W-LHo 16 , J-L Wang 17 , S-T Lin 18 , Y-L Hsieh 19 , S-C Wang 8 , H-H Chang 3 ,Y-L Yang 3 , F-L Huang 9 , C-Y Chang 18 , W-H Chang 20 and K-S Lin 3,201 Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; 2Department of Hematology–Oncology, Chang Gung Children’s Hospital–Linkou,Taoyuan, Taiwan; 3 Department of Pediatrics, National Taiwan UniversityHospital, Taipei, Taiwan; 4 Department of Pediatrics, National Cheng KungUniversity Hospital, Tainan, Taiwan; 5 Department of Pediatrics, Chang GungChildren’s Hospital–Kaohsiung, Kaohsiung, Taiwan; 6 Department of Pediatrics,Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 7 Department ofPediatrics, China Medical University Hospital, Taichung, Taiwan; 8 Departmentof Pediatrics, Changhua Christian Hospital, Changhua, Taiwan; and 9Department of Pediatrics, Veterans General Hospital–Taichung, Taichung,Taiwan; 10 Department of Pediatrics, Veterans General Hospital-Taipei, Taipei,Taiwan; 11 Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan; 12Department of Pediatrics, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan;13Department of Pediatrics,Tri-Service GeneralHospital,Taipei,Taiwan;14 Department of Pediatrics, Veterans General Hospital-Kaohsiung, Kaohsiung,Taiwan; 15 Department of Pediatrics, Koo Foundation Sun-Yat-Sen CancerCenter, Taipei, Taiwan; 16 Department of Pediatrics, Shin Kong Wu Ho-SuMemorial Hospital, Taipei, Taiwan; 17 Department of Pediatrics, WanfangHospital Taipei Medical University, Taipei, Taiwan; 18 Department of Pediatrics,Taipei Medical University Hospital, Taipei, Taiwan; 19 Department of Pediatrics,Cathay General Hospital, Taipei, Taiwan; and 20 Childhood Cancer Foundationof the R.O.C., Taipei, TaiwanOBJECTIVES: To improve the treatment results of childhood acutemyeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) inTaiwan by Taiwan Pediatric Oncology Group (TPOG) nation-widestudies while preserving quality of life.METHODS: From Jan. 1997 to May 2009, there were 332 childrenwith AML: 44 with acute promyelocytic leukemia (APL), treated withcurrent protocols, 283 with non-APL AML treated with TPOG AML97A, a novel protocol, and 5 with AML and Down syndrome. FromJan. 2002 to May 2009, 989 children with ALL were enrolled inTPOG-ALL-2002 studies. The stratified therapy according torisk-group was given to 387 standard-risk (SR), 334 high-risk (HR)and 268 very-high-risk (VHR) patients. Randomization of one or tworeinduction courses in SR patients was performed. The database ofAML and ALL used for analyses was last updated on 31 August 2009.MAIN RESULTS: In AML patients, the 5-years overall survival (OS)was 57.5 + 3.1% (s.e.) and the 5-year event-free survival (EFS) 53.0 +3.1%. Stem cell transplantation done in first remission showed asimilar outcome as chemotherapy alone. In ALL patients, the 5-yearOS was 83 + 1.5% and the 5-year EFS 78 + 1.6%. In SR patients, 140received 2 courses of reinduction while 149 received one course. Theoutcomes were similar. Prophylactic cranial irradiation was much lessused between 2002 and 2008, and has completely been omitted sinceJan. 2009.CONCLUSIONS: The treatment results in both childhood AML andALL in Taiwan are comparable to results being reported worldwide.The lower frequencies of ETV6-RUNX1 and hyperdiploidy (>50chromosomes) in Taiwanese children with ALL warrant further study.[Keywords]acute myeloid leukemia,acute lymphoblastic leukemia,treatment results90

FP10-02A REVIEW OF CHILDHOODMEDULLOBLASTOMA: THE HONG KONGPAEDIATRIC HAEMATOLOGY / ONCOLOGYSTUDY GROUP (HKPHOSG) EXPERIENCEFROM 1999 TO 2008Chan Godfrey Chi-Fung 1 , Shing Matthew Ming-Kong 2 ,Yuen Hui-Leung 3 , Li Rever Chak-Ho 4 , LingSiu-Cheung 5 , Ha Shau-Yin 1 , Li Chi-Kong 2Departments of Paediatrics & Adolescent Medicine, 1 Queen Mary Hospital,The University of Hong Kong; 2 Prince of Wales Hospital, The ChineseUniversity of Hong Kong, 3 Queen Elizabeth Hospital, 4 Tuen Mun Hospital,5 Princess Margaret Hospital (Hong Kong)OBJECTIVES: Medulloblastoma is the most commonbrain tumor in childhood with relatively good prognosis iftreated with multi-modality approach. We reviewed ourlocal experience on this tumor.METHODS: Nearly all local children (≤18yrs) with braintumor were treated by the 5 public hospitals involved inthis study. The data was collected prospectively from thedata manager of the HKPHOSG and further confirmedwith the Hong Kong Cancer Registry.MAIN RESULTS: From Jan 1999 to Dec 2008, a total of287 childhood brain tumors were diagnosed locally.Medullobastoma alone accounted for 57/287 (20%) of allof our childhood brain tumors. It is more common in boy(M:F=33:23) and the median age was 5.8yrs (range 0.2 –17.2yrs). After excluding 2 non-local and 3 >15yrschildren, the incidence of medulloblastoma was 4.7children/million children ≤15yrs. In our patient cohort,desmoplastic (n=2) and large cells histology (n=1) wereuncommon. 21/57 (36.8%) had large tumor (Chang’sstaging T3) and 17/57 (29.8%) had leptomeningeal spread(M1-3, M3 n=10) at diagnosis. 7 children

FP10-04CHARACTERIZATION OFNEUROBLASTOMA USING F-18-DOPAPET/CTMeng Yao Lu 1 , Kai-Yuan Tzen 2 , Shiann-Tarng Jou 1 ,Hsiu-Hao Chang 1 , Yung-Li Yang 1 , Kai-Hsin Lin 1 ,Dong-Tsamsn Lin 1 , Wen-Ming Hsu 31 Dept of Pediatrics, 2 Dept of Nuclear Medicine, 3 Dept of Surgery, NationalTaiwan University Hospital, Taipei, TaiwanOBJECTIVES: Tumors of ganglion cell origin includingganglioneuroma, neuroblastoma and ganglioneuroblastomaare common tumors in children. Iodinated MIBG and FDGPET-CT are the choice for functional imaging studies. Inthe recent year, F-18 DOPA has emerged as a newdiagnostic tool for neuroendocrine tumors. We try to applyand characterize the functional status of the neuroblastomain limited number of cases of our institution.METHODS: After 100 mg of carbidopa was given orallyfor 60 mins, the patients was injected with 200 MBq (5.4mCi) of F-18-DOPA and wait for 90 mins for imaging.Whole body imaging was performed using PET/CT. Thepatients also received the standard I123-MIBG, FDGPET-CT imaging studies.RESULTS: Nineteen patients with neuroblastoma wereenrolled in this study. Their ages ranged from 0.5-12.8years old. All patients had F-18-DOPA PET scan. Threepatients were primary diagnosis/staging of disease and 16cases were restaging of disease. Three primary diagnosispatients showed positive uptake of F-18-DOPA in primaryand metastasis lesions. In restaging patients, five patientswithout uptake of F-18-DOPA showed negative standardimaging studies. Eleven patients with uptake ofF-18-DOPA showed only 6 positive I123-MIBG and 7positive FDG PET/CT. In organ-region-specific analysis,there were different uptake pattern in 3 imaging studies.CONCLUSIONS: No study on the possible role ofF-18-DOPA in neuroblastoma has been published yet. Inour study, we found a major drawback of FDG PET/CTwas lack of visualization of lesions in the liver andcranium because of high physiologic activity. Anotherdisadvantage of FDG PET/CT was not disease-specific.F-18-DOPA is a better substrate for the cell membranenorepinephrine transporter than MIBG and a more specificsubstrate for neuroblastoma cells than FDG. F-18-DOPAmight provide more additional information than FDGPET/CT in this area. F-18-DOPA positivity indicates theability of tumor cells to accumulate and the ability todecarboxylate F-18-DOPA by AADC in a welldifferentiated tumor or tumor component. This mightindicate better prognosis. The clinical significance needsfurther follow up.[Keywords]Neuroblastoma, F-18-DOPA PET/CTFP10-05IRINOTECAN AS A CANDIDATE IN THESALVAGE REGIMEN FOR ACUTELYMPHOBLASTIC LEUKEMIAHiroaki Goto 1 , leo Tanoshima 2 , Hiromi Kato 3 , TomokoYokosuka 4 , Masakatsu Yanagimachi 5 , Ryosuke Kajiwara 6 ,Shumpei Yokota 7Department of Pediatrics, Yokohama City University Hospital 1 , Pediatrics,Yokohama City University 2,3,4,5,6 , Deaprtment of Pediatrics, Yokohama CityUnivrersity School of Medicine 7 ( Japan)BACKGROUND: B cell-precursor acute lymphoblastic leukemia(BCP-ALL) is the most frequent malignant disease in children.Childhood BCP-ALL can be cured by chemotherapy. Howeverthere remain relapse or refractory diseases, and the salvageregimens for those are limited. The camptothecin analog,topotecan, has been shown to be effective against relapse ALL.Our recent study using the cell lines suggested the activity ofirinotecan, the other camptothecin analog, in BCP-ALL.AIM: To investigate the role of irinotecan in a salvage therapy forBCP-ALL.MATERIALS AND METHODS: Two BCP-ALL cell lines,YCUB-2 and YCUB-4, and 12 clinical leukemic samples obtainedfrom childhood BCP-ALL patients were used. The cytotoxicity ofSN38, an active metabolite of irinotecan, or other drugs wasevaluated by the MTT assay or the flow cytometricchemosensitivity assay (FCCA). (1) To evaluate the time or dosedependence of SN38 cytotoxicity, YCUB-2 cells were exposed toSN38 at 1 to 10 ng/ml for 1 to 18 hours, then washed and grown inthe medium without SN38. At 48 hours after the start of culture, %survival compared to untreated control was measured by theFCCA. (2) To evaluate the effects of SN38 in combination withother drugs, YCUB-2 or YCUB-4 cells were cultured for 4 dayswith SN38 combined with2-fluoroadenine-9-β-D-arabinofuranoside (F-ara-A), etoposide(ETOP), cytosine β-D-arabinofuranoside (AraC), or4-hyroperoxy-cyclophosphamide (CPM) at differentconcentrations. The combination effects of two drugs wereassessed by an improved isobologram method. (3) The cytotoxicityof SN38 was compared to that of topotecan in the BCP-ALLclinical samples by the FCCA after 2 days culture.RESULTS: (1) SN38 inhibited the growth of YCUB-2 cells in thetime- and dose-dependent manner, although it failed to showcytotoxicity at the low (1ng/ml) concentration even after longexposure. The effect of SN38 correlated significantly with relativeAUC (P < 0.001). (2) SN38 was found to have a synergistic oradditive effect with CPM. In contrast, SN38 acted only additivelywith F-ara-A, ETOP, or AraC. (3) Among the BCP-ALL clinicalsamples, the sensitivity to SN38 correlated significantly with thatto topotecan (P = 0.008).CONCLUSIONS: We could not show the advantage of usingirinotecan over topotecan in the series of the BCP-ALL clinicalsamples, however, there were some cases which respondedpreferentially to SN38. Our results suggest that it may bebeneficial to develop the combination chemotherapy of irinotecanand cyclophosphamide as a salvage regimen for BCP-ALL.[Keywords] acute lymphoblastic leukemia, B cell precursor, irinotecan, SN38,cell line92

FP10-06INVASIVE ASPERGILLOSIS IN CHILDRENWITH HEMATOLOGICAL DISEASES ANDCANCERS: A 13-YEAR REVIEW IN A SINGLEINSTITUTIONShih-Hsiang Chen 1,3 , Chao-Ping Yang 1,3 , Tang-HerJaing 1,3 , Iou-Jih Hung 1,3 , Cheng-Hsun Chiu 2,3 ,Yhu-Chering Huang 2,3 , Tzou-Yien Lin 2,31 Division of Pediatric Hematology/Oncology, 2 Division of PediatricInfectious Disease, Department of Pediatrics, Chang Gung MemorialHospital, Taoyuan, Taiwan; 3 College of Medicine, Chang Gung University,Taoyuan, TaiwanOBJECTIVES: Invasive aspergillosis (IA) is alife-threatening infection in children with hematologicaldisorders or cancers. The clinical features and treatmentoutcome for these children are rarely analyzed in Taiwandue to small case numbers.METHODS: We retrospectively reviewed the medicalrecords of children treated at our Hematology-Oncologydepartment who had IA between January 1997 and October2009. The patient characteristics, clinical presentation,antifungal treatment, and outcome were assessed. Thediagnosis of IA was based on the microbiological findings,radiological and pathology reports. The category of IA(proven, probable, or possible) was determined by theEORTC criteria.MAIN RESULTS: Seventeen children with IA wereidentified (7 proven, 5 probable, and 5 possible). Themedian age was 11.2 years (range 1.7 – 15.2 years). Themost common underlying diagnosis was acute myeloidleukemia (9 children), followed by acute lymphoblasticleukemia in 4, neuroblastoma in 2, and severe aplasticanemia in 2. Among 15 children with cancer, 9 werediagnosed at relapsed/refractory status. All except onepresented with lung involvement. Six patients underwentbiopsy from nasal cavity or lung for histology proof. Only5 Aspergillus species were identified from fungus culture(4) or internal transcribed spacers sequencing (1).Aspergillus flavus accounted for 4, and the remaining oneis Aspergillus fumigatus. Before 2004, Amphotericin-Bwas the only drug of choice. It was replaced byvoriconazole or caspofungin/micafungin as the first-linechoice for IA. Five (29.4%) patients were recovered fromIA. One patient died of complications of bone marrowtransplantation, 2 died of sepsis (Staphylococcus aureusand Stenotrophomonas maltophila, respectively), and 2survived to date. The overall survival rate for IA in thisstudy was 11.8%.CONCLUSION: Despite improvement of diagnosticmodalities and antifungal therapy, the prognosis ofchildren with IA is dismal. Effective antifungalprophylaxis, early diagnosis of IA, and rapid recognition ofAspergillus species and susceptibility may benefit thesepatients.FTRP1-01DESIGN AND APPLICATIONS OF ANTI-IgETHERAPYTse-Wen ChangDistinguished Research Fellow, Genomics Research Center, Academia Sinica,TaiwanSince the anti-IgE therapeutic concept was conceived in1987, the lead product, omalizumab, a humanizedantibody with a unique set of binding specificities, hasbeen studied in more than 50 Phase II and III clinicaltrials in various allergic indications. Omalizumab (tradename Xolair) has been approved in the USA, EU,Taiwan and many other countries for treating patients 12years and older with severe allergic asthma. Xolair hasalso been approved in EU in 2009 for treating patients 6to 11 years old with severe allergic asthma. Omalizumabhas been shown to be efficacious for treating allergicrhinitis in many organized, corporate-sponsored,placebo-controlled Phase II and III trails. Xolair hasbeen shown to be efficacious in treating atopic dermatitisand urticaria in about 10 case series studies coveringover 50 patients. In several major trials, Xolair has beenshown to reduce the anaphylaxis risks and enhance theefficacy of allergen-based desensitizationimmunotherapy. More than 100,000 patients with severeallergic asthma, whose symptoms cannot be controlledeven with high doses of corticosteroids, have beentreated with omalizumab. In Taiwan, Xolair wasapproved for treating patients 12 years and older withsevere allergic asthma in 2007 and a payment policy wasissued by the Health Insurance Bureau in 2008. A fewhundred patients with severe allergic asthma have beentreated with Xolair in major medical centers withresponse rates estimated to be over 80%. In Taiwan, asmall number of patients with severe atopic dermatitishave also been treated with Xolair in off-label uses withgenerally good results.In this presentation, the “Skewed Antigen ExposureTheory” for explaining the increase of allergic disease inmodern societies will be introduced. In the main body ofthe talk, the rationale for designing the anti-IgE drug, thestructural basis for the unique set of binding specificityof anti-IgE, the main pharmacological effects of theanti-IgE drug, the clinical indications in which anti-IgEhas been tried, and the combination of anti-IgE andimmunotherapy as a new therapeutic approach will bediscussed.[Keywords]Aspergillosis, Cancer, Children,Non-malignant hematological disease93

FTRP1-02RECNET ADVANCE ON MOLECULARMECHANISMS AND DIAGNOSIS OFHENOCH-SCHOLEIN PURPURABor-Luen CHIANGProfessor, National Taiwan University, TaiwanFTRP1-03EARLY RECOGNITION AND MOLECULARDIAGNOSIS OF IMMUNODEFICIENCIESWen-I LeePrimary Immunodeficiency Care And Research (PICAR) Institute, PediatricAllergy & Immunonology & Rheumatology Department, Cha-ng Gung Memoryand Children's Hospital, TaiwanHenoch-Schönlein purpura (HSP) is a commonsystemic small vessel vasculitis in childhood;however, there have been few nationwideinvestigations. Further, the real immunopathogenicmechanisms of HSP are yet to be defined. In the pastseveral years, we have studied the levels ofautoantibody in HSP patients for the clarification ofpathogenic mechanism of HSP. For theepidemiological study, the data of this study werederived from the research database of Bureau ofNational Health Insurance, Taiwan. From Jan 1999to Dec 2002, children younger than 17 years of agewith the diagnosis of HSP were recruited into thisstudy. Data of each patient including sex, age, date ofonset, length of hospitalization, and medical chargewere recorded and analyzed. We have also studiedthe levels of IgA anti-cardiolipin and anti-endothelialcell antibody in the HSP patients. The frequency ofTGF- secreting T cells in HSP patients was alsoanalyzed in the study. Polymorphisms of TGFpromotergene were also analyzed between HSPpatients and normal controls. In our studies, wefound that Childhood HSP in Taiwan was lessfrequent than the previous British report. HSP occurscommonly in autumn and winter; and in 3 to 12 yeasold children. The data also demonstrated that IgAanti-cardiolipin and anti-endothelial cells antibodycould also be detected in HSP patients. Mostrecently, we also identified the promising antigenicpeptides for the diagnosis of Henoch-Scholeinpurpura. We aim to set up the diagnosis kit forHenoch-Scholein purpura for the assessment ofdisease activity and long-term follow up of thepatients with Henoch-Scholein purpura.AIMS: Recent advances in immunological techniques have lead toincreased recognition of primary immunodeficiency diseases (PIDs). Inthis longitudinal study, we have attempted to describe the distribution,clinical features and molecular bases of PIDs in Taiwan for earlyrecognition.MATERIALS AND METHODS: Patients diagnosed as the codes ofthe International Classification of Disease, Tenth Revision (ICD-10)and reported as the literatures were all enrolled since 1985. In additionto clinical manifestations and immunological functions, molecular andcandidate-gene analysis were evaluated in selected patients afterinformed consents had been obtained.RESULTS: One hundred and eighty-seven patients (from 170families) diagnosed as PIDs were enrolled from mainly five tertiarymedical centers. The distribution by an update eight categories showed49 patients (15 females/34 males; 26.2%) with “predominant antibodydeficiencies”, 32 patients (6/26; 17.1%) with “T- and B-cellimmunodeficiency”, 21 patients (6/15; 11.2%) with “congenital defectsof phagocyte”, 65 patients (17/48; 34.8%) with “other well-definedimmunodeficiency syndromes”, four patients (2/2; 2.1%) with “diseasein immune dysregulation” (Chediak-Higashi syndrome in 2; familialhereditary hemophagocytosis in 1 and Immunodeficiencypolyendocrinopathy enteropathy and X-linked in 1) and 15 patientswith complement deficiencies (6/9; 8.0%). None had “defects in innateimmunity” or “autoinflammatory disorders”. Pseudomonas andSalmonella spp. were the two most identified microorganisms insepticemia (41.0%; 32/78 episodes). Twenty-eight patients (15.0%) hadmortality. Hematopoietic stem cell transplantation succeeded in 12 of19 patients. In addition to 29 patients with DiGeorge syndromerecognized by FISH, direct sequencing identified 19 unique mutationsfrom 42 families, reflecting distinct Taiwan geography, although aselection bias may exist.CONCLUSIONS: Compared with Western countries, higherpercentage of unique mutations (19/42; 45.2%) implies geneticdiversity in Formosa island. However, Taiwanese PIDs patients with“predominant antibody deficiencies” are the second common, but“other well-defined immunodeficiency syndromes” are much more.Both “defects in innate immunity” and “autoinflammatory disorders”are not found. Adult PIDs patients with common variableimmunodeficiency are few, but more popular in Western country. Thisstudy to date reflects underestimation of disease load. Early suspicionfor a diagnosis of PIDs makes possible early definitive therapy andavoids the complications of pretreatment infections or autoimmunity.In Wisconsin, newborn screening has included patients with severecombined immunodeficiency (SICD) and/or 22q11 deletion syndromefor timely transplantation in the first 3.5 months of SCID life.94

FTRP1-04MOLECULAR AND GENETICINVESTIGATION ON AUTOIMMUNEDIABETES: FROM MECHANISMDISSECTION TO CLINICAL APPLICATIONHuey-Kang Sytwu, MD, PhDGraduate Institute of Microbiology and ImmunologyNational Defense Medical Center, Taipei, TaiwanInsulin-dependent diabetes mellitus (IDDM), or type I diabetes, isa T cell-mediated autoimmune disease. A widely used animalmodel for dissecting immunopathologic mechanisms in IDDMand developing preventive and/or therapeutic strategies is thenon-obese diabetic (NOD) mouse, an inbred strain thatspontaneously develops autoimmune diabetes resembling humanIDDM. To directly dissect the immunopathogenic mechanisms oftype I diabetes and to develop potential therapeutic strategy forthis autoimmune disease, we have already established severalnovel transgenic and knockout NOD mice in our lab: one is theTh1 and Th2 double transgenic NOD mouse which provides thebest in vivo model to study the pathogenic nature and thedifferentiation of helper T cell subsets during the diabetogenicprocess in IDDM;the other is the IL-12 knockout NOD mousewhich provides the best model to investigate directly theregulation of IL-12 on autoimmune response in NOD mice. Tofurther delineate the protective roles of some novel immunemodulatory molecules, such as soluble decoy receptor 3 (DcR3),cytotoxic T lymphocyte antigen 4 (CTLA4), program death ligand1 and 2 (PD-L1 and 2), heme oxygenase 1 (HO-1), in theautoimmune process and search for potential preventive and/ortherapeutic targets in this disease, we generated (a) insulinpromoter (pIns)-sDcR3 transgenic NOD mice, (b) pIns-singlechain anti-CTLA4 transgenic NOD mice, (c) pIns-single chainanti-4-1BB transgenic NOD mice, (d) pIns-PD-L1 transgenicNOD mice (e) pIns-PD-L2 transgenic NOD mice (f) pIns-HO-1transgenic NOD mice. Making full use of these unique mousestrains, we are quantitatively and qualitatively investigating theimmunopathogenic mechanisms of autoimmune diabetes andprovide valuable information for the development of novelimmunotherapies. Meanwhile, by using the established lenti-viralsystem in our lab, we are currently transducing variousimmunomodulatory genes into islets and investigating the functionand survival of these genetically modified graft islets. This mayprovide tremendous help for successful islet transplantation in thefuture. Finally, we are also generating target gene-specificlenti-siRNA-mediated knockdown NOD mice and investigatingpotential role of those genes in immunopathogenic process in typeI diabetes. To delineate further the potential roles of (1) somenovel immunopathogenic cytokines, such as IL-23 and IL-27; (2)some immunomodulatory receptors such as TLR-4; (3) some Th1response-inducing genes, such as T-bet, or STAT1/4, inautoimmune diabetes, we generated functional knockdown NODmice insufficient for those genes via direct lenti-siRNAtransduction or direct microinjection of shRNA constructs in NODembryos. Now we already obtained IL-23 and IL-27 knockdownNOD mice and currently investigate their phenotypes. These novelknockdown NOD mice will provide the best models to investigatedirectly the regulation of those genes on autoimmune immuneresponse in NOD mice.FTRP2-01STUDIES FROM ENTEROVIRUS 71 INFECTIONSTO KAWASAKI DISEASE IN TAIWANLuan-Yin CHANGAttending Physician, Division of Pediatric Infectious Disease, Department ofPediatrics, National Taiwan University Hospital, TaiwanThe enterovrius 71 (EV71) outbreak in Taiwan in 1998 is very well-knownto cause a lot of fatal children cases. In 1998 epidemic, there were 405severe cases with 78 deaths. In 2000 to 2002, there were still dozens of fatalEV71 cases each year. In addition, in 2008 EV71 outbreak occurred againin Taiwan as well as in mainland China and there were hundreds of severecases and dozens of fatal cases. A stage-based management was thusdeveloped to reduce the case-fatality but most survivors of brainstemencephalitis plus cardiopulmonary failure might have neurologic sequelaeand impaired cognition.We studied 433 family members from 94 families in which EV71 positivelyisolated. The overall enterovirus 71 transmission rate of household contactswas 52% (176/339): 84% (70/83) siblings, 83% (19/23) cousins, 41%(72/175) parents, 28% (10/36) grandparents and 26% (5/19) uncles/aunts.So, enterovirus 71 household transmission rates are high for children,medium for parents and low for other adults. Being male and being lessthan 6 years old were associated with increased risk of EV71 infection.Continuous EV71 disease and laboratory surveillance is warranted to allowfor possible earlier control and prevention measures.Kawasaki disease (KD) is the most important worldwide acquired heartdisease in children after the incidence of rheumatic heart disease isdecreasing during the recent decades. There is some mystery in KD such asdifferent incidences in different countries, the easy involvement of coronaryarteries and the unsolved infectious pathogen. We propose that infectionwith a single pathogen or infection with certain pathogens may triggerKawasaki disease in certain hosts (more in the male, young children, andthe oriental), and the infection may be transmitted within households, andthe majority have only mild illness but only a small percentage of childrenwith certain host genetics will develop Kawasaki disease.To investigate the infectious etiology of Kawasaki disease, a prospectivecase and household cohort study for Kawasaki disease is ongoing. The KDcases received virological isolation, molecular workup includingpolymerase chain reaction (PCR) for pan-enterovirus, pan-coronavirus,rhinovirus, metapneumovirus, pan-adenovirus and other possible viruses,cDNA RDA (representational difference analysis-subtractive cloning),VIDSICA (virus discovery based on the cDNA amplified restriction-lengthpolymorphism) and viral gene chips for unknown pathogens, bacterialculture (blood, throat swabs and stool: bacterial culture and stored strain forfurther toxin or superantigen detection), and serological workup for themost potential pathogen. Household members of KD cases were asked toundergo screening by virus isolation of throat swabs, and received the firstblood sample during acute illness of the KD case, and second blood sampleduring the convalescent stage of the KD case. If specific potential pathogenis found in Kawasaki cases, samples from the household members will beworkup for the specific pathogen.Till now, a total of 229 KD cases and about 900 of their household membershave been enrolled. During 1 to 10 days prior to their KD illness, 53.9%cases had contact with ill household members, and 10.3% had positivecontact with extra-familial ill people. In 59% families, at least one otherfamily member had illness after KD cases’ disease onset.95

FTRP2-02IMMUNOPATHOGENESIS OF EV71,DENGUE, SARS AND NOVEL H1N1INFECTIONSKuender D. YangProfessor & Chair, Department of Medical Research, Chang GungMemorial Hospital at Kaohsiung, and Chang Gung University, TaiwanChanges of global ecology expose humans to novelpathogens for emerging infections arising frommicrobial mutation, vector-borne and/or zoonotictransmission. The authors have encountered andstudied four emerging infections includingenterovirus 71 encephalitis, dengue hemorrhagicfever and severe acute respiratory syndrome (SARS)and novel influenza A (H1N1) in the past decade.Here they described and summarized immunemechanisms of common emerging infections intofour categories: 1) host naïve immunodeficiencywith disseminated infection; 2) earlyimmunosuppression with and without lateraugmented immunity; 3) augmented innate immunitywith vascular insults; and 4) cross-enhancement ofsecondary heterotypic infections. A practical guide toidentify the fatal mechanism of an emerginginfection is described to early diagnose and earlytreat the life-threatening infection. Based on theevolution of common emerging infections, a 4-stepstrategy is formulated for the prevention of apotential emerging infection during pre-outbreak,sporadic early outbreak, endemic outbreak andpandemic outbreak.FTRP2-03COMMUNITY-ASSOCIATEDMETHICILLIN-RESISTANT STAPHYLOCOCCUSAUREUS IN TAIWAN AND THE WORLDYhu-Chering HuangChang Gung Memorial Hospital and Chang Gung University, Kweishan, TaiwanStaphylococcus aureus is an important pathogen in humans and causesa broad spectrum of diseases, ranging from skin and soft tissueinfection to life-threatening infections of septicemia, necrotizingfasciitis, and toxic shock syndrome. Methicillin-resistant S. aureus(MRSA) is usually considered a nosocomial pathogen, and if acquiredin the community, most infections were traditionally confined toindividuals with health care-associated risk factors. However, thechanging epidemiology of MRSA became evident in the 1990s whenMRSA infections occurred in previously healthy children withoutestablished risk factors for MRSA acquisition. The term“community-associated” (CA) MRSA infection was used to describethis disease entity.CA-MRSA was first reported from infections in remote populations inAustralia, and in the USA by the end of the 1990s. Since then, MRSAinfections have also been reported from Europe, the near East, Asia andOceania. CA-MRSA strains have been recognized as a novel pathogenwhich is genetically different from the healthcare-associated (HA)MRSA in the US. They are usually characterized by limited antibioticresistance (except to β-lactams), possess different exotoxin geneprofiles (e.g. Panton-Valentine leukocidin, PVL), carry type IV or Vstaphylococcal cassette chromosome (SCCmec IV, V), and the majorclinical manifestations are usually cellulitis and abscess. However,CA-MRSA clones vary in different continents, countries and evenareas; for example, clones with multilocus sequence types (ST) 1(USA400) and 8 (USA300) are mostly found in the United States andCanada, clones with ST80 are mostly found in Europe, while cloneswith ST30 are found worldwide, including US, Europe, Oceania,Japan. CA-MRSA has become a matter of concern worldwide, inparticular in the USA.In Taiwan, CA-MRSA, though not uncommon, had not drawn anyconcern in 1990s until cases of fatal infections in children werereported in Minnesota and North Dakota in the US. CA-MRSAinfections have been increasingly reported in pediatric patients since2000. The rate of methicillin resistance among CA S. aureus infectionsin children without risk factors increased from 9.8% between 1999 and2000 to 56% between 2004 and 2005. Likewise, the nasal carriage rateof MRSA among previously healthy children increased significantlyfrom 1.9% in 2001 to 10.2% during the period 2007 to 2008. Theincreasing trend of nasal MRSA colonization prevalence might accountfor the increasing incidence of CA-MRSA infection in children inTaiwan. Most CA-MRSA clinical isolates in Taiwan are geneticallydifferent from HA-MRSA isolates and are characterized by ST59 or itsvariant ST338, a specific pulsed-field gel electrophoresis (PFGE)pattern (similar to USA 1000), resistance to clindamycin anderythromycin, containing a specific type of SCCmec (type V T , alsotentatively designated as type VII lately) gene, and possessing PVLgenes.96

FTRP2-04IMPROVING CHILD HEALTH: BRIDGINGRESEARCH AND PRACTICECheng T. ChoProfessor Emeritus, Department of Pediatrics,University of Kansas Schoolof Medicine, USAThe goal of pediatric research is to improve child health.Clinical investigators have traditionally played a major role intranslating new knowledge from research into clinicalpractice. However a significant gap between research andpractice remains, for there are many barriers to gettingresearch findings into science-based clinical practice. Clearlyfurther efforts are needed to find the most effective strategiesfor bridging the gap between research and practice. Flexner’sreport (1910) transformed medical education and medicalresearch in the United States. Recent recommendations(“Crossing the Quality Chasm)” by the Institute of Medicine(2001) will undoubtedly have a significant impact onimproving quality of health care in the years ahead.Knowledge derived from basic research, translationalresearch, and clinical trials have formed the scientific basis ofour contemporary medical practice. Activities to improve andenhance patient care (such as outcomes research, health caredelivery research, and behavioral research) have also attractedmuch attention in recent years. It is likely that these effortswill also help to bridge the gap between research and practice.Steps needed to move from research to practice involvesynthesis of new research findings, creation of evidence-basedclinical policies, and application of policies (guidelines) inpractice. It is apparent that our ability to generate criticalevidence-based guidelines is limited and often inadequate.Thus practice guidelines often generate more questions andcontroversies and are infrequently followed in practice.Obviously the guidelines cannot replace the physician’sdiscriminatory skills and critical thinking. It is increasinglyclear that physicians must be trained to identify pertinentliterature and resources and to find answers that are lacking inthe “evidence-based “guidelines. In a highly commercializedenvironment, it is also known that commercial interest candistort interpretations of the scientific evidence and henceresponses to it. Special efforts should be made to support thedevelopment of practice guidelines without conflict of interest.Past history indicates that there is mostly one-way diffusion ofmedical discovery and knowledge from university tocommunity. More work is needed to bring practice to researchin order to capture potentially valuable insights andobservations that might be offered by the practicing cliniciansin the community.Barriers and challenges to bridging the gap between researchand practice are many. Most of these barriers relate tophysicians, patients, and health system, and will requirecontinued efforts to find coherent solutions to the challenges.Future goals should also include supporting programs thatattract and retain clinical investigators andphysician-scientists, promoting effectiveness research, andimproving quality of health care.Saturday 17 AprilPL-02HEPATITIS C IN CHILDREN – PATHOGENESISAND TREATMENTKathleen B. SchwarzProfessor of Pediatrics, Director of the Pediatric Liver Center, Johns HopkinsUniversity School of Medicine, USAOver the last two decades, there has been increasingrecognition of Hepatitis C as a major public health problem inadults affecting ~170 million worldwide. Although the numberof children infected worldwide is not known, it has beenestimated that there are 30 – 60,000 cases of active infection inthe United States alone. Maternal-fetal transmission is themajor route by which children are infected and occurs in ~4%of pregnancies in HCV+ women. It has been estimated that thisform of transmission is responsible for 10 – 50,000 new casesannually on a global basis. HCV is the leading reason for livertransplantation in the US and one of the leading causes of livercancer worldwide. HCV in childhood has a 50 – 85%chronicity rate. There is usually mild liver disease duringchildhood. However, since 1988, 133 liver transplants havebeen performed in US children for HCV liver disease and therehave even been a few cases of liver cancer. Certain pediatricgroups, such as street youths have higher prevalence rates (upto 5%) vs the prevalence in US children which is 0.2 – 0.4%.The life cycle of the HCV virus is well-known and will bediscussed. The pathology of the liver of HCV-infected childrenshows a range of inflammation and fibrosis. HCV genotype IIIand/or obesity are particularly associated with steatosis.Special pediatric HCV issues include whether or not breastfeeding is permitted and when children of HCV+ mothersshould be screened. Although HCV RNA is rarely found inbreast milk, breast feeding is permissible as long as the motherdoes not have cracked or bleeding nipples. Children of HCV+mothers should be screend by Elis at 18 months of age. Thetreatment of choice for children with HCV is pegylatedinterferon plus ribavirin. Results in children with genotype I,which is the most resistant to interferon, show that about halfdevelop a sustained viral response (no detectable HCV RNA 6months after stopping therapy.) Children with genotypes 2 or 3have a much higher likelihood of response – perhaps 70 – 80%.Children with genotype 1 require 12 months of therapy; adultswith genotypes 2 or 3 only require 6 months of therapy.Although this has not been studied in children with HCV it islikely that they too would respond to only 6 months treatment.There are newer, very promising specific antiviral agentscurrently being tested in adults in combination with pegylatedinterferon and ribavirin, including serine protease inhibitorsand polymerase inhibitors. Pediatric trials with thesecombinations have not yet been performed but are eagerlyawaited.97

PL-03TRANSLATIONAL RESEARCH: FROMBENCHSIDE TO BEDSIDEYonghao Gui, MD., MSc.Children’s Hospital of Fudan University, Shanghai, China 201102PL-04CANCER PREVENTION – STARTING FROMCHILDHOODMei-Hwei Chang, M.D.Department of Pediatrics, National Taiwan University Hospital, Taipei, TaiwanThe translation of theoretical knowledge and experimentalbreakthroughs into the clinical practice of medicine hasalways been difficult. During the past few decades, growingbarriers between clinical and basic research, the size of theacquired scientific data and the ever-increasing complexitiesof conducting clinical research according to governmentregulations and financial constraints, have made thistranslation even more problematic. Translational research hasemerged as a scientific discipline rather recently, in order tobridge the gap between basic and clinical research. Thetranslational researcher functions as the link or translatorbetween the two branches having experience of both fields andtranslating the messages of one branch into the language of theother. The translational researcher can identify the underlyingclinical consequences of the new discoveries of basic research,and can relate them to the confirmed needs of the clinician.Thus, translational research is currently defined as the processof transforming research innovations into new health productsand diagnostic and therapeutic methods, and is usually carriedout in academic institutions.Recent studies indicated that the discoveries in basic orclinical science take a very long time to translate towidespread application and to improved health of individuals.There are two major “translational blocks” impeded theincorporation of scientific discoveries: 1. translation formbasic science to human studies (new methods for diagnosis,treatment or prevention). 2. translation form clinical studies toactual clinical practice decision making. Pediatrics aboundswith examples of the slow translation of research to improvedhealth care. Despite research highlighting preventable causesof childhood asthma, successive national and internationalguidelines for asthma management, and effective therapies,studies continue to document the rising prevalence of asthma,variability in the level of health care received by children, andalso the significant of asthma morbidity. Investigations haveuncovered genetic, biologic, and behavioral cause ofchildhood obesity or autism, yet effective human studies areneeded to prevent and successfully manage these disease, Inthe long term, only education can modify mentalities andperceptions. Through educational interventions new strategiesof clinical and translational research can be implemented at alllevels, including collaboration between scientists, clinicians,researchers and stakeholders (industry, society, state, healthsystems). Via education, the hospital manager will cease toidentify clinical research with low-priority andnon-cost-effective expense. Society will understand the truebenefits of medical research. Scientists and clinicians willaccommodate to public control and transparency of prioritiesand fund expenses. Finally, industry will invest more, andthose in medical fields will learn to recognize the necessitiesof private sector investment. But again, as mentioned before,the roles of translational clinicians and researchers are central.Cancer is a leading cause of death in human. Main riskfactors of cancer includes: (1) Host genetic factors.;(2)Lifestyle or environmental factors, such as food, physicalactivities, smoking, alcohol, aflatoxin, arsenic, asbestos,ultraviolet, and ionizing radiation, etc.; (3)Infection: such ascarcinogenic virus, bacteria, or parasite infection.While the incidence of cancer is much higher in adults, theaction of cancer prevention can be started from childhood.Besides screening of the genetic factors to find out the highrisk groups for specific cancers, establishment of healthylife styles starting from childhood to prevent obesity,exposure to environmental carcinogens such as smoking,alcohol, radiation, etc. are also very important.Among the infectious agents with carcinogenic evidences,successful vaccines have been developed for hepatitis Bvirus (HBV) and human papilloma virus (HPV). Vaccinesare still developing for other viruses (such as, hepatitis Cvirus, EB virus, human immunodeficiency virus), andbacteria (H. pylori).Immunization against carcinogenic biologic agents is a costeffective way to prevent cancer. HBV vaccine is the firsthuman cancer preventive vaccine with high efficacy. Livercancer is one of the five leading causes of cancer deathglobally. Due to mother-to-infant transmission as the mainroute of chronic HBV infection and liver cancer,immunization since birth is the best timing to prevent livercancer. We have provided evidences to support the successof reduction of chronic HBV infection and liver cancer inchildren. Recently, we have also proved that the cancerpreventive effecto fo HBV immunization has been extendedfrom children to adolescents of 6 to 19 years old. Thisexperience could be shared with other cancer preventivevaccines, such as HPV vaccine to prevent cervical cancer,in the future.In conclusion, cancer preventive works should be startedfrom early childhood.98

PL-05CLINICAL ASPECTS OF PEDIATRICRESEARCH IN ENTEROVIRUS 71INFECTIONSTzou-Yien LinSuperintendent, Professor Chang Gung Children’s Hospital, Chang GungCollege of Medicine, TaiwanClinical research is a key force to steer the progress ofcurrent medicine. From the very beginning, patientshave never stopped being our best teachers. However,excellent research can only occur in the context ofexcellent services. By closely observe the clinicalcourse of the patient and record carefully, pediatriciancan conduct excellent clinical studies. I will take ourstudy of enterovirus 71 as an example.Enterovirus 71 (EV71) was first isolated in 1969. Sincethen, it has been associated with several outbreaks inBulgaria (1975), Hungary (1978), Malaysia (1997) andTaiwan (1998). After eradication of poliovirus, EV71will become the most important enterovirus that causesfatalities and sequelae in children.A severe outbreak of EV71 infections occurred inTaiwan in 1998. There were 405 severe cases with 78deaths. The outbreak occurred in Taiwan almost eachyear since 2000. We have found most children withEV71 infections presented with hand, foot, and mouthdisease or herpangina. Some progressed to CNSinvolvement, and only a few of them further advancedto cardio-pulmonary failure. If they survived, severeneurological sequelae may develop. The risk factors forCNS involvement are lethargy and fever for more than3 days, and for cardiopulmonary failure after CNSinvolvement are hyperglycemia, leukocytosis and limbweakness. Those risk factors may alert pediatrician tohospitalize high risk children as early as possible.We have conducted a long term follow-up study ofchildren with cardiopulmonary failure after CNSinvolvement. Sixty-four percent had limb weakness andatrophy, 61% needed tube feeding, 57% neededventilator support, 75% had delayed developmental and50% had lower intelligence. We also identifiedHLA-A33 was associated with susceptibility to EV71infections.With the development of stage-based management, themortality rate decreased from 19 % in 1998 to 15 % in2001, and 3.8 % in 2008. But the neurological sequelaehave increased. Vaccination is the only way to controlEV71 outbreak. A cohort study in Taiwan showed thatseropositive rate of EV 71 in pregnant women was65%, in neonates was 50%, and the rate decreased to1.2% in infants age 6 months. This study suggested thatthe target age for inactivated EV71 immunizationwould be infants younger than 6 months of age.MS5-01ISSUES IN THE TREATMENT OF PEDIATRICCHRONIC KIDNEY DISEASE IN JAPANOsamu UemuraHead of Pediatrics, Aichi Children’s Health and Medical Center, JapanProgress in methods of treating chronic kidney disease (CKD) is beingmade worldwide. The purpose is to improve prognosis of the CKDpatient and reduce the cost of medical care. To this end, the JapanAssociation of Chronic Kidney Disease Initiative was founded in 2006,and the Committee of Measures for Pediatric CKD within the JapaneseSociety for Pediatric Nephrology was founded in the same year.Since urinalysis at schools was started in Japan in 1974, the incidenceof chronic glomerulonephritis has decreased amongst childrenundergoing dialysis therapy by the induction method, and that ofcongenital diseases such as hypoplastic/dysplastic kidney and refluxnephropathy has increased. The latter now accounts for about 40% ofend-stage renal disease. Therefore good communication andcooperation between pediatric nephrologists and pediatric urologists isindispensable in controlling childhood CKD.To further advance CKD treatment measures it is important forpediatric nephrologists to know their CKD patients’ renal function. InJapan, measurement of serum creatinine in children is now performedby the enzyme method, making the establishment of a facility for renalfunction evaluation essential.In our Children’s Health and Medical Center, we previously found asignificant positive correlation between serum creatinine (Cr)concentration and body length in children aged 1–12 years, with bodylength (m) × 0.30 yielding a value similar to the reference serum Crlevel. Muscle mass tends to be less correlated with body length andincreases rapidly from puberty into adolescence and beyond, especiallyamongst males. Neonatal glomerular filtration rate (GFR) per bodysurface area is about 1/3 of that of adults. It becomes equal to that ofadults at about 18 months old. When we evaluated renal function ofunder-1 year olds and over-12 year olds, we could not find a reliablecorrelation coefficient for body length, and thus further investigation ofthese age groups is necessary in the future. We found that referenceserum cysC levels gradually decreased during the first year after birth,thereafter becoming constant. Mean serum cysC concentration inchildren aged 1 year (0.76±0.10 mg/L) was slightly higher than inchildren aged ≥2 years (0.70±0.09 mg/L).For adults, pharmacotherapeutics such as angiotensin-convertingenzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs)have been shown to be effective in non-diabetic nephropathy as well asdiabetic nephropathy. These same treatments are generally adopted forchildhood CKD, but there is no corresponding evidence of similarefficacy.The Committee of Measures for Pediatric CKD has embarked on amultidisciplinary study to determine the reference value of serumcreatinine and cystatin C, as well as on a randomized controlled trial toinvestigate methods of slowing progression of CKD in Japanesechildren.99

MS5-02OPTIMIZING OUTCOMES IN PEDIATRICCHRONIC KIDNEY DISEASE PATIENTSHui-Kim, YapShaw-NKF-NUH Children’s Kidney Centre, University Children’s MedicalInstitute, National University Health System and Dept of Pediatrics, YongLoo Lin School of Medicine, National University of SingaporeThe long-term survival of children on dialysis is similar totransplant patients during the first 5 years, however,cumulative survival after 10 years is significantly worse inchildren on dialysis. In fact, cardiovascular andcerebrovascular complications are the major causes ofdeath in young adults with childhood onset chronic renalfailure (CRF). Studies have shown the presence ofadvanced coronary and carotid arteriopathy in young adultswith childhood-onset CRF. Coronary calcium scores andintima-media thickness have been shown to be associatedwith cumulative dialysis and ESRD time, and cumulativeserum calcium-phosphate product. Althoughlong-standing hypertension is an important determinant ofconcentric left ventricular hypertrophy, hypertension alsoresults in increase in arterial wall tension, contributing tothe development of arteriosclerosis and myocardialischaemia. However, anemia also worsens eccentric leftventricular hypertrophy, often seen in volume overloadstates, by increasing the left ventricular chamber size andstroke volume. Anemia also increases the arterialdiameter, and could conceivably lead to an increase inarterial wall thickness, worsening the arteriosclerosis. Inaddition, metastatic calcification due to increasedcalcium-phosphate product will lead to progressivecoronary calcification contributing to the myocardialdysfunction. Therefore it is important to control bloodpressure, correct anemia and control mineral bone diseaseas all these will contribute to the long-term cardiovascularmorbidity. In a recent study aimed at determining thesignificant factors present during the period of chronickidney disease (CKD) stages 2-5 in pediatric patients,which may affect cardiovascular status at the time ofend-stage renal disease (ESRD), 46 pediatric patients,mean age 9.70±6.48 years at diagnosis of CKD and meanCKD duration of 3.65±3.74 years were retrospectivelyreviewed. 54.3% of patients had at least oneechocardiographic abnormality at onset of ESRD, withsevere left ventricular hypertrophy (left ventricular massindex; LVMI >51g/m 2.7 ) occurring in 21.7%. Althoughsystolic and diastolic blood pressure indices showedsignificant correlation with LVMI and cardiac functionalstatus (fractional shortening and ejection fraction)respectively, only time-averaged uric acid was a significantpredictor (p=0.002) of LVMI on multivariate analysis. Thismay be related to the long-term proinflammatory effects onvascular cells. Therefore control of uric acid in CKDpatients may conceivably have a role in improvinglong-term cardiovascular outcomes.MS5-03ESTABLISH THE MANAGEMENT MODEL OFPEDIATRIC CHRONIC KIDNEY DISEASE INTAIWANChing-Yuang LinAssociate Dean, College of Medicine, China Medical UniversityChief, Division of Pediatric Nephrology, China Medical University Hospital,TaiwanBACKGROUND: The prevalence of children on renalreplacement therapy (RRT) continues to increaseworldwide. Mortality rates among children onend-stage renal disease (ESRD) are 150 times greaterthan those in the general pediatric population. Moreover,date comparing the survival of pediatric patients whoreceived either peritoneal dialysis (PD) or hemodialysis(HD) are spare. Most large scale of chronic kidneydisease (CKD) from on adult and seldom on children.AIM OF THE STUDIES: (1) To examine the long-termsurvival and outcome of children treated for ESRD inTaiwan and compared the PD and HD groups (2) tofollow-up children with heavy proteinuria and asses riskfactors of CKD and renal progression (3) to build thescreen system for early detection of the CKD childrenand construct CKD shared-care system and build bycaring model (from early detection, follow-up to monitornetwork).RESULTS: The annual pediatric ESRD incidence ratewas 8.12 per million of age-related populations.Compared with adult ESRD, pediatric ESRD patientshad less cardiovascular deaths (22.2% vs. 32.3%,ρ=0.200), but were more prone to succumb tocerebro-vascular disease (17.8% vs. 7.8%, ρ=0.021). Wefollow-up 5,351 children with heavy proteinuria for 10to 15 years. There were 328 [6.13%] children in CKDstage I, 2,931 [54.77%] in stage 2, 1,868 [34.91%] instage 3, 66 [1.23%] in stage 4 and 39 [2.22%] in stage 5.Cumulating rate of ESRD and mortality were increasing,especially in CKD stage 3.The prevention scheme for children at risk for CKD anddialysis outcome was also designed.100

MS5-04THE CHARACTERISTICS OF IQ ANDSELF-CONCEPTS FOR CHILDREN WITHCHRONIC KIDNEY DISEASE IN TAIWANChian-Fang CherngDepartment of Health Psychology, Chang Jung Christian University,TaiwanAIMS OF THE STUDY: Not only physical development couldbe retarded in children with chronic illness, progress of chronicillness may also affect negatively on psychological developmentin those afflicted children. The current study aimed to examine thedifferences between the children with kidney diseases and thematched healthy children on their psychological development interms of intelligence and self-concept. Our findings could assistmedical experts and caregivers to understand mental needs of thechildren with kidney diseases and critical factors influencing theirsocial and psychological development.METHODS: Two hundred and fifty-three children were invited toparticipate in the study. Among them, 215 children were afflictedwith kidney diseases (kidney group), and 38 healthy children wererecruited from community (non-kidney group). Approximatelyone half (130 out of 253) of the subjects were assessedindividually by Wechsler Intelligence Scales (IQs), and over 90%of the subjects (235 out of 253) were asked to respond theresearcher-made self-concepts questionnaire. In sum, there were110 children whom had been completely assessed by both IQs andself-concepts questionnaire.MAIN RESULTS: Employing factor analysis method, theself-concepts were clustered into 12 factors, including havingcompany, good friend, shy self, bad kid, rigid self, fat-and-shortself image, bad habit, physical symptoms, optimist, talent,confidence, and not easy-going. When t-tests were used toexamine the differences on the 12 factors between these twogroups, the results showed that their scores on 5 factors weresignificantly statistically different. Specifically, children in thenon-kidney group had significantly higher scores on the havingcompany (t=2.57, p

MS6-02MLL TRANSLOCATION: EPIGENETICLANDSCAPES IN THE DEVELOPMENT OFACUTE LEUKEMIAQianfei WangBeijing Institute of Genomics, Chinese Academy of Sciences, ChinaThe MLL (mixed-lineage leukemia) gene encodes ahistone methyltransferase that is frequently targetedby chromosomal translocations in aggressive formsof acute leukemia. MLL associated leukemias arevery prominent in infants (age

MS7-01CURRENT ISSUES IN NEONATAL JAUNDICEWu-Shiun HsiehAssociate Professor, National Taiwan University Hospital and NationalTaiwan University College of Medicine, TaiwanHyperbilirubinemia is the most common condition that requiresevaluation and treatment in newborn infants. Increased bilirubinproduction in neonates can be due to shortened erythrocyte lifespan, larger erythrocyte volume, heme degradation from the fetalextramedullary hematopoietic tissue, immaturity of hepatic uptakeand intracellular transport, and increased enterohepatic circulation.The risk factors associated with hyperbilirubinemia aremultifactorial that include exclusive breastfeeding,glucose-6-phosphate dehydrogenase deficiency, ABO hemolyticdisease, oriental ethnicity, early onset jaundice observed within 24hours after birth, cephalohematoma, adrenal hemorrhage,significant bruising, late preterm gestational age, and history of aprevious sibling treated with phototherapy.Identifying among newborns at risk to develop markedhyperbilirubinemia is a clinical challenge. Total serum bilirubin isusually the standard method for detecting the bilirubin levels.However, blood sampling for measuring total serum bilirubin byheel sticks may induce pain and potentially result in infection inthe neonates. The incidence of severe hyperbilirubinemia amongthe East Asian neonates is higher than the Caucasian neonates andrepeated measurements by heel stick may be necessary in theoriental neonates. Transcutaneous measurement of bilirubin is aviable option in screening neonates to determine if they are at riskfor hyperbilirubinemia, but the correlation between thetranscutaneous bilirubin detection and total serum bilirubinremains controversial especially when the total serum bilirubinlevel is beyond 11mg/dL (188μmole/L). Most clinicians regardedtranscutaneous bilirubin measurement only as a screening tool forsevere hyperbilirubinemia. We evaluate the accuracy oftranscutaneous bilirubin measurement and try to establish thecutoff point of transcutaneous bilirubin levels that require totalserum bilirubin measurement.Parents usually face a paradox when they are feeding their newlyborn infants: They are told that breast milk is best andbottle-feeding maybe hazardous to health. But breast-fed babiesare more likely to become jaundiced than bottle-fed babies, and atrisk of developing kernicterus. Prospective study exploring theimpact of breastfeeding and formula supplements on neonataljaundice may provide important information concerning thefeeding paradox. East Asian and American Indian neonates are atrisk of neonatal hyperbilirubinemia suggesting that genetic factorsare involved in the development of neonatal hyperbilirubinemia.Uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) isthe one of the key enzymes for bilirubin conjugation, andmutations of UGT1A1 cause the unconjugated hyperbilirubinemiasyndromes known as Crigler-Najjar syndrome and Gilbert'ssyndrome. Homozygous A (TA) 7 TAA variation in promoter regionof UGT1A1 gene was found to be associated with neonatalhyperbilirubinemia in western people. However, the highallele-frequency of Gly71Arg, but not promoter polymorphism, inUGT1A1 gene was found to be responsible for neonatalhyperbilirubinemia in Japanese, Koreans and Taiwanese studies.We will discuss the impacts of various feeding modes on neonataljaundice and provide information concerning that whether thereare interactions between genetic polymorphism of UGT1A1 geneand breastfeeding itself, or the fasting effect, in affectingcirculating bilirubin levels in the first week of life based on studyfrom single medical center in Taiwan.MS7-02UPDATE OF BILIARY ATRESIAKathleen B. SchwarzDirector of the Pediatric Liver Center and Professor of Pediatrics,Johns Hopkins University School of Medicine, USABiliary atresia (BA) is an infantile obliterative cholangiopathyof unknown etiology. It is the most common pediatric liverdisease leading to liver transplant. Research efforts of theBiliary Atresia Research Consortium (BARC)(a multi-centerconsortium funded by the National Institute of Health in theUnited States) have focused on attempts to understand etiologicfactors and determinants of outcome. There are three majortypes of BA (Group I – no anomalies; Group II – majoranomalies without splenic malformation; Group III – splenicmalformation). These three groups differ as to certain clinicaland demographic features, suggesting different etiologies forthe three groups. There has been progress in the investigationsof etiologies (viral, autoimmune, genetic) from both animaland human studies. The rotavirus (RV) mouse model has beenparticularly helpful and has shown that administration ofrhesus RV to newborn Balb C mice results in an immunemediated attack against the biliary system involving bothcellular and humoral immunity. Gamma interferon is also a keyinflammatory factor since gamma interferon knockout mice donot develop BA when given RV. RV does result in a productiveinfection of human cholangiocytes with release of IL-8, aneutrophil chemoattractant. BARC has also investigatedclinical determinants of outcome. Bilirubin at 3 months postKasai is predictive of clinical outcome at two years and age

MS7-03INTRAHEPATIC CHOLESTASIS- TODAY ANDTOMORROWHuey-Ling Chen, M.D., Ph.D.Associate Professor, Department of Pediatrics, National Taiwan University,College of Medicine and Hospital, Taipei, TaiwanCholestasis is a common manifestation of inherited or acquiredliver diseases in pediatric patients. Recent advances inunderstanding the molecular mechanisms of bile transport andphysiology have facilitated the diagnosis of many cholestatic liverdiseases previously thought to be idiopathic. Highly diverseetiologies and overlapping symptoms make the diagnosis ofpediatric cholestasis challenging.The primary etiologies of intrahepatic cholestasis includeinfectious diseases, inherited liver transport disorders, metabolicdisorders, ductal-plate malformations, chromosome anomalies andendocrine disorders. Ischemia, drugs and parental nutrition havealso been indicated as secondary causes of intrahepaticcholestasis. Progressive familial intrahepatic cholestasis (PFIC) isa group of disorders characterized by early onset cholestasis,progressive liver cirrhosis and hepatic failure during the first orsecond decade of life. Within this group, three types of geneticdefects have been identified. Characterized by low serum GGTlevels, PFIC-1 and -2 are caused by mutations in the ATP8B1(FIC1) and ABCB11 (BSEP) genes, respectively. PFIC-3 ischaracterized by high serum GGT levels and is caused by geneticmutations in ABCB4 (MDR3). Inborn errors of bile acid synthesisresult in a deficiency of primary bile acids and abnormal bile acidmetabolites, resulting in progressive intrahepatic cholestasis andlow serum bile-acid levels. The above-mentioned geneticdisorders are also responsible for minor forms of cholestatic liverdiseases in adults: benign recurrent intra-hepatic cholestasis,drug-related cholestasis, intrahepatic cholesatsis of pregnancy, andcholesterol gall-bladder stones.Aberrant ductal formation during the development of the livercontributes to unique forms of intrahepatic cholestasis. Alagillesyndrome is an autosomal dominant disorder caused by JAG1 orNOTCH2 mutations. Intrahepatic ductal paucity, peripheralpulmonary artery stenosis, and other organic anomalies arecharacteristic of this syndrome. Other forms of ductal platemalformation can also cause intrahepatic cholestasis andfibrocystic diseases of the liver and kidney.A recently discovered neonatal cholestatic disorder caused bycitrin deficiency (NICCD) was found to be more prevalent inAsian countries. Common mutations, including 1638ins23 and85del4 in the SLC25A13 gene were found in Asian patients.Heterozygous carriers of these mutations are prevalent in thenormal population. Cholestasis is resolved during the first year oflife in most patients. Occasionally, some patients are affected byadult-onset type II citrullinemia (CTLN2).The treatment for intrahepatic cholestasis includes nutritionaltherapy and choleretic agents. Donor shortage and higher surgicalrisks for infants pose challenges for patients in need of livertransplantation. Nuclear receptors are being investigated aspotential therapeutic agents for intrahepatic cholestasis.Hepatocyte transplantation is also under experimentalinvestigation.MS7-04LIVER TRANSPLANTATION IN CHILDREN:RECENT ADVANCESSeng-Hock QuakDepartment of Paediatrics, University Children’s Medical Institute,National University Hospital, SingaporeOrthotopic liver transplantation (OLT) is the treatment option forpatients with end stage liver disease and is widely accepted inmany Asian countries. The results of OLT is excellent with longterm survival rate of well above 80%. The quality of life after OLTis extremely good and the vast majority of the recipients are able tofunction normally without much limitation to their daily activities.Organ shortage is a major problem in OLT and many of thepatients expired before a donor organ is available. As such,surgical techniques using split liver and living donors areimportant advances in recent years. The surgical outcome of thesetwo procedures is comparable to those using cadaveric grafts.Organ rejection is always a problem in transplantation. In fact thesuccess of OLT is greatly enhanced by the discovery ofanti-rejection medications such as cyclosporine and tacrolimus.However these medications are known to have a number of seriouscomplications including renal toxicity. A number of newer drugswhich are less nephrotoxic are now available.Infection is an important issue in OLT. There are a number of riskfactors which include pre-transplant malnutrition, poor immunefunction in patients with end stage liver disease and the operationitself. Immediately after the operation, the recipient is usuallyintubated with many invasive intravenous lines and drainage tubes.The use of anti-rejection drugs also suppresses their immunefunction. Other than bacterial infection, viral infection and fungalinfections are particularly problematic among the recipients. Theuse of prophylactic gancyclovir has greatly reduced the rates ofsymptomatic cytomegalovirus (CMV) infection. Risk factors forfungal infections include multiple operations, CMV infection,prolonged antibiotics usage and multiple rejections.Hepatitis B infection had been a contraindication for OLT.However, patients with hepatitis B infection are suitable for OLT inrecent years because it is possible to control viral replication withthe use of nucleoside analog, hyperimmune gammaglobulin andvaccination. In recent years, OLT is a treatment option for patientswith liver cancer, provided that the cancer is confined to the liverand not more than certain acceptable size. In children, Ebstein Barrvirus and Herpes infections are common. These infections areassociated with post-transplant lymphoproliferative disease(PTLD). Fortunately in many patients, the PTLD would improve ifthe immunosuppressants are reduced in time. Monoclonalantibodies can be used to treat PTLD and the outcome issatisfactory.In conclusion, neonatal and infantile cholestasis is a commondisorder with highly diverse etiologies, making the diagnosis achallenge for clinicians. Research is been carried out to improvediagnosis and treatment, as well as to elucidate the etiology ofcryptogenic diseases104

MS8-01NOVEL BIOLOGICAL THERAPIES FORINHERITED DISEASE INCHILDREN: LESSONS FROM ANIMALMODELS AND CLINICAL STUDIESBarry J. ByrneProfessor and Associate Chair of Research, Department of Pediatrics andMicorbiology and Molecular GeneticsVirginia Root Sutherland Professor of CardiologyDirector, Powell Gene Therapy CenterMedical Director, Congenital Heart CenterUniversity of Florida, College of Medicine, USAEarly presentation of cardiac dysfunction and thediagnosis of primary cardiomyopathy in infancy andchildhood is most often associated with a geneticetiology. An increasing number of causative geneshave been characterized in patient populations and havebeen studied mouse and other animal models. Thegenetic mechanisms in these conditions are both gain ofgene function and loss of gene function. The ultimategoal of determining the molecular mechanism of adisease is to develop a specific treatment based on amolecular medicine that treats the underlying geneticdefect. The basic principle of gene therapy is to usegene transfer or gene correction to address theunderlying cause of disease.Several examples of cardiac gene transfer will be usedto illustrate the clinical relevance of this approach andhow such approaches can be applied to inherited causesof cardiac dysfunction as well as rhythm disturbances.The focus of the discussion will be on viral vectormediated gene transfer using the non-pathogenicparvovirus, AAV.Early phase clinical studies using AAV vectors areunderway in the US, EU and Taiwan as well as anumber of studies involving gene modification of stemcells. The pathway to clinical application will also beemphasized as part of the presentation.MS8-02NOVEL TREATMENTS AND LESSONS INLYSOSOMAL STORAGE DISEASESYoshikatsu EtoDepartment of Genetics & Genome Science, Tokyo Jikei University,School ofMedicine, Tokyo, JapanLysosomal Storage diseases (LSD) are caused by a singlelysosomal enzyme deficiency which results in theaccumulation of a certain compounds such as glycolipids,mucopolysaccharides or glycopeptides in lysosomes. Morethan 60 different LSDs have been described in theliteratures. Treatment options have been increased greatlyrecently; these are enzyme replacement therapy(ERT),hematopoietic stem cell therapy, (HSCT) chemicalchaperon therapy, substrate reduction therapy gene therapyand etc.Enzyme replacement therapy are now widely used in manyLSD patients such as Gaucher, Fabry, Pompe, MPS I, II, VIdiseases. However, there are drawbacks with ERT.: theseare high costs, IgG antibody formation toward CRIMnegative patients and no efficacy to CNS involvement. Onthe other hand, HSCT does cross the blood brain barrier, butposes problems, such as GVHD, rejection and etc.Chaperon therapy has some benefit (oral administration),but limited efficacy to the type of mutation.Substrate reduction therapy such as Zavesca and Genz hasbeen explored to Gaucher, Fabry and Pompe diseases. Theresults seem to be also limited in their efficacies.Novel treatments such as exon skipping procedure (PTC)and SiRNA may be also explored in future. Gene therapyusing AAV vector has been carried out in patients withCeroid lipofucinosis and possibly in metachromaticleukodystrophy.by lenti virus vector. Now, number oftreatment choices for the patients with LSD are available,but there are still currently being evaluated situation.In summary, molecular medicines for inheritedcardiomyopathy and other childhood diseases relies onan understanding of the molecular pathophysiology ofthe disease. Novel techniques for gene therapy or genecorrection in several forms of pediatric cardiomyopathyare currently being evaluated in early phase clinicaltrails.105

MS8-03EMERGING THERAPIES FORNEUROPATHIC LYSONSOMAL STORAGEDISORDERSSeng H. ChengGroup Vice President, Genetic Diseases Science, Genzyme Corporation,USAWhile systemic administration of recombinant enzymescan be effective at treating the visceral disease associatedwith several lysosomal storage disorders, this approachdoes not adequately address the CNS component becauseof the limited ability of the hydrolases to traverse the bloodbrain barrier. To overcome this limitation, we haveinvestigated alternate delivery strategies such as directadministration of the enzymes into the CNS, and evaluatedother technology platforms including gene and smallmolecule therapies. Our experience withintracerebroventricular administration of recombinant acidsphingomyelinase (ASM) into the CNS of Niemann-Pick Amice showed that this route of delivery could result inbroad dispersion of the therapeutic throughout the CNS.Near-global correction of the storage pathology wasrealized in the CNS of the treated mice with consequentimprovement in motor function. Amounts of the enzymewere also detected in the serum with resultant partialcorrection of the visceral disease suggesting that direct andperiodic delivery of enzyme into the brain may be anapproach to treating this disease. We have extended theseobservations to mouse models of late-infantile Battensdisease and neuropathic Gaucher disease suggesting thatthis therapeutic paradigm may be broadly applicable toother lysosomal storage disorders. Intracerebroventriculardelivery of the respective lysosomal enzymes into thesemice reduced the levels of the offending substrates in theCNS with consequent improvement in motor behavior andnotable extension of their life spans. As the therapy isnecessarily invasive and chronic, we have evaluated thepotential of substrate reduction therapy as an adjuvanttherapy in the management of a subset of these neuropathiclysosomal storage disorders. Earlier preclinical studieshave indicated that small molecule inhibitors ofglucosylceramide synthase can be successfully deployed toreduce the frequency of enzyme infusions for treating theglycosphingolipidoses. While the orally available inhibitor(Genz-112638) that is presently tested in non-neuropathicGaucher patients is incompatible for delivery to the CNS,we have explored other chemical scaffolds that may bemore conducive to traversing the blood brain barrier. Oraladministration of one such inhibitor (Genz-529648) intoSandhoff mice was effective in delaying the progression ofthe disease and extending their longevity. Hence, acombination of enzyme and substrate reduction therapiesmay be employed to optimally manage the CNSmanifestations associated with a subset of theglycosphingolipidoses. Current efforts are directed atdetermining if these encouraging observations in thediseased mouse models are translatable to larger animals.FP11-01PHOSPHORYLATION-DEPENDENTMEMBRANE INSERTION AND ACTIVATION OFTRPC6 IS REGULATED BY A BALANCEBETWEEN NEPHRIN AND PLC-G1SHOICHIRO KANDA 1 , YUTAKA HARITA 2 , TAKASHISEKINE 3 , TAKASHI IGARASHI 4 , TAKAFUMI INOUE 5 ,SEISUKE HATTORI 6Department of Pediatrics, The University of Tokyo 1 , Department of MolecularBiology, Yokohama City University, Graduate School of MedicalScience 2 ,Department of Pediatrics, Toho University Ohashi Medical Center 3 ,Department of Pediatrics, The University of Tokyo 4 , Department of Life Scienceand Medical Bioscience, Waseda University 5 , Department of Biochemistry,School of Pharmaceutical Sciences, Kitasato University 6 (JAPAN)In kidney, blood is filtered through glomeruli forming a primitiveurine. Recent studies revealed that the intercellular junction betweenthe glomerular epithelial cells, called slit diaphragm (SD), is themolecular constituents of this glomerular filter, and that the majorcomponent of SD is an SD-specific transmembrane protein, Nephrin.Mutations of a podocyte slit diaphragm (SD) component, TRPC6, havebeen reported to cause focal segmental glomerulosclerosis (FSGS)(Winn M, et al. Science, 2005). However, the mechanism how thechannel activity of TRPC6 is involved in the pathogenesis remainsunclear, because some mutations in TRPC6 enhance its activity, whileothers do not (Reiser J, et al. Nat. Genet, 2005). Meanwhile there areaccumulating lines of evidence that SD serves as a platform conductingphosphorylation-mediated signals. TRPC6 is also tyrosinephosphorylated by Src family kinases and its phosphorylationupregulates its channel activity (Hisatsune, et al, J Biol. Chem, 2004).During the investigation of the role of the phosphorylation of SDcomponents, we found that Nephrin binds to phosphorylated TRPC6,and this interaction is disrupted in disease-causing TRPC6 mutations,suggesting the role of the phosphorylation-dependent interaction in thepathogenesis. The phosphorylation of the tyrosine residue critical forthis interaction was also essential for the insertion of TRPC6 in theplasma membrane. The same tyrosine residue was one of thePLC-gamma1 binding sites, and PLC-gamma1 was necessary for thephosphorylation-dependent membrane traffic of TPRC6. Coexpressionof Nephrin in cultured cells disturbed the TRPC6-PLC-gamma1interaction and interfered the surface expression and the channelactivation of TRPC6. These results indicate that Nephrin blocked theTRPC6-PLC-gamma1 interaction, and suppressed thephosphorylation-dependent surface expression and channel activationof TRPC6. Interestingly, the phosphorylation-dependent surfaceexpressions and channel activation of disease-causing TRPC6mutations were not abrogated by Nephrin. Thus, TRPC6 channelactivity may be regulated by a balance between inhibitory Nephrin andstimulatory PLC-gamma1, and the disease-specific mutations shift thebalance toward the excess TRPC6 channel activity, which mayunderlie the development of FSGS.These data not only propose a model by which TRPC6 mutations causepodocyte injury, but also may indicate the possibility that downregulation of Nephrin observed in most proteinuric states may causedysregulation of calcium homeostasis. Furthermore, our result thatNephrin blocks TRPC6 activation may provide a novel strategy oftreatment for injured podocytes in future (under filing a patentapplication).[Keywords]TRPC6, Nephrin, phosphorylation, calcium homeostasis106

FP11-02GENE EXPRESSION AND CYTOKINEPROFILING OF DEC1-TRANSFECTEDJURKAT CELLS: ELUCIDATING THEPOTENTIAL MECHANISM OF ACTION OFDEC1 IN THE PATHOGENESIS OF MINIMALCHANGE NEPHROTIC SYNDROMEWee-Song Yeo 1 , Ai-Wei Liang 2 , Chang-Yien Chan 2 ,Tarun K Maheshwari 2 , Caroline GL Lee 3 , Stanley CJordan 4 , Hui-Kim Yap 1,21 Department of Pediatrics, University Children’s Medical Institute, NationalUniversity Health System, Departments of 2 Pediatrics and 3 Biochemistry,Yong Loo Lin School of Medicine, National University of Singapore,4 Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles,USA.OBJECTIVES: We have previously shown that in patients withminimal change nephrotic syndrome (MCNS), the Deleted inEsophageal Cancer 1 (DEC1) gene expression was significantlyupregulated in CD4+ T-cells of patients with relapse as comparedto those in remission. In order to further elucidate the role ofDEC1 in relapse of MCNS, we explored differential geneexpression profiles using cDNA microarray following transfectionof DEC1 into Jurkat cells and the cytokine expression profile ofDEC1-transfected Jurkat cells.MATERIALS & METHODS: Jurkat cells were transfected withDEC1 gene using SuperFect Transfection Reagent (Qiagen). RNAwas isolated from the transfected cells, reverse transcribed andhybridized into Agilent cDNA microarray. After normalization andstatistical analysis of the data the differentially expressed geneswere further analyzed and classified using Ingenuity PathwaysAnalysis into functional categories and pathways. For cytokineexpression profiling of DEC1-transfected Jurkat cells, Jurkat cellstransfected with DEC1 and plasmid alone (plasmid control) werecultured at 5 x 10 6 cells/ml for 72 hours. Cytokine levels in thesupernatants were then assayed utilizing the multiplex suspensionbead array system.RESULTS: Of 3326 genes that were differentially expressed, 546genes showed expression above 2-fold. DEC1-transfected Jurkatcells differentially expressed molecules that regulate biologicalfunctions like cell signaling (37 molecules, p=0.004), moleculartransport (67 molecules, p=0.004), cellular assembly andorganization (34 molecules, p=0.005). The analysis also showed agreater than 1.5-fold increase in molecules involved in the NF-κBsignaling pathway. In addition, there was also a greater than 2-foldincrease in GATA-3 expression, an inducing factor for Th2polarization. Cytokine profiling of DEC1-transfected Jurkat cellsdemonstrated a 110% increase in IL-5 level as compared toplasmid controls. There was also a 95% increase in IL-4 levels inDEC1-transfected Jurkat cells, as compared to plasmid controls.CONCLUSION: The above findings suggest that the mechanismof action of DEC1 in the pathogenesis of MCNS may be mediatedvia the NFκB and GATA-3 pathways. IL-4, IL-5 and IL-13 arefound in a gene cluster, regulated coordinately by GATA-3. Thefindings of increased IL-4 and IL-5 levels in DEC1-transfectedJurkat cells are in accordance with an increase in GATA-3 geneexpression, further supporting the role of Th2 polarization in thisdisease.FP11-03THE ROLE OF TLR PATHWAYS IN IMMUNEESCAPE OF THE RATS MODEL OFRESPIRATORY SYNCYTIAL VIRUS NEPHROTICSYNDROMEJin Wu 1 , Zheng Wang 2Dept. of Pediatrics, West China second Hospital, Sichuan University 1 , Dept. ofPediatrics, West China second Hospital 2 (China)OBJECTIVE: To search for evidence of respiratory syncytialvirus (RSV) immune escape and explore the correlation ofmechanism of RSV immune escape and TLR signalingpathway in nephrotic syndrome of rats induced by RSV.METHODS: 1Rats were inoculated with 6×10 6 PFU RSV andsacrificed on days 4,8,14,30,60,90,120 postinoculation. RSV Fgene and protein were detected in kidney, lung and spleen withreal-time quantitative RT-PCR and indirect IF staining. 2Ondays 4,8,14,30,60,90,120 postinoculation, theTLR3,TLR4 ,NF-κB and IL-13, IFN-γ gene and protein inkidney, lung, Spleen were detected with real-time quantitativeRT-PCR, indirect IF staining, flow cytometry or ELISAmethod. Finally we analyzed the correlations between TLRpathway and RSV persistent.RESULTS: 1After inoculation, the Proteinuria increased andthe fusion of foot processes resemble human MCNS. 2120days after inoculated, RSV F protein could been found inkidney, spleen, lung (RSV 120 △Ct: kidney 10.333±3.251, lung10.917±1.625, spleen 8.917±1.530). 3TheTLR3(RSV 120 △Ct:kidney 2.3±0.273;spleen 4.25±1.604),NF-κB and IL-13 (RSV 120 △Ct:kidney 13.916±3.967;spleen10.9±2.701) showed significantly higher in kidney and spleenof RSV 4 , RSV 14 , RSV 90 , RSV 120 (Fig1). compared with thecontrol ( N 120 △Ct: TLR3: kidney 7.167±0.577; spleen8.167±0.764; IL-13: kidney 21.333±1.155; spleen18±2.645)(p0.05).TLR4 and IFN-γ were only significantlyhigher in kidney or/and spleen of RSV 4 or/and RSV 14compared with the control(p0.05).CONCLUSION: The persistent of RSV was mostly caused bythe suppression of TLR4 --which is a major pathway inimmune response and partly associated with suppression ofTLR3 pathway. RSV infection might interfere with TLRpathway, which resulting in Th1/Th2 migration,down-regulation of IFN-γ. This may be another importantmechanism for RSV immune escape.[Keywords]TLR pathways; immune escape; respiratory syncytialvirus; nephrotic syndrome[Keywords]Gene expression, cytokine profiling, DEC1-transfected Jurkatcells, pathogenesis, minimal change nephrotic syndrome107

FP11-04DIFFERENTIAL EFFECTS OF NITRIC OXIDEDEFICIENCY ON HYPERTENSION ANDKIDNEY DAMAGE IN SPONTANEOUSHYPERTENSIVE RATSYou-Lin Tain 1 , Li-Tung Huang 1 , I-Chun Lin 1 , Jia-FuHong 1 , Ying-Tong Lau 21 Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung,Chang Gung University, Taiwan; 2 Physiology and Pharmacology, Collegeof Medicine, Chang Gung University, TaiwanBACKGROUND: Hypertension (HTN) is the major riskfactor for the development of kidney disease. We hypothesizethat nitric oxide (NO) deficiency is involved in thedevelopment of HTN and hypertensive target organ damage.NO deficiency can be due to decreased nitric oxide synthase(NOS) expression, inhibition by asymmetric dimethylarginine(ADMA, an endogenous NOS inhibitor), inhibition by proteininhibitor of neuronal NOS (PIN), and inactivation by oxidativestress.METHODS: Using spontaneous hypertensive rat (SHR), agenetically hypertensive model, different causes of NOdeficiency were determined in the SHR and their controlWKY rats at three stages: 4 wk-old (pre-hypertensive), 12wk-old (hypertensive), and 24 wk (hypertensive target organdamage).RESULTS: Systolic and diastolic blood pressures of SHRwere significantly higher than those of age-matched WKY ratsexcept at 4 weeks of age. No differences in the creatinine leveland kidney weight/BW were observed between SHR andWKY rats at three stages, demonstrating target organprotection in the kidney in SHR persists until 24wks of age.The neuronal NOSα (nNOSα) abundance was lower in the24-wk-old SHR vs. WKY rats. The renal cortical nNOSβabundance was mild decreased in SHR at three differentstages. In addition, renal cortical endothelial NOS (eNOS)abundance was lower only in the 4-wk-old SHR than that inage-matched WKY rats. Renal cortical PIN expression washigher in SHR than that in WKY at 12-wk-old. Plasma ADMAlevels were higher in SHR than those in WKY at all threegroups. In contrast, plasma L-arginine to ADMA ratio (AAR)was significantly decreased in SHR. In the kidney, plasmaL-citrulline levels were significantly lower in SHR than thosein WKY at 4 wks and 24 wks of age, whileargininosuccinate-synthetase and -lyase (ASS & ASL)expression were increased in SHR at 12 wks of age.Interestingly, SHR exhibited increased ADMA and decreasedAAR in the kidney at 4wks of age, which can be preserved at12 wks and 24 wks of age. Renal immunostaining of 8-OHdG,an oxidative DNA damage marker, in SHR were apparentlystronger than those in WKY at three stages.CONCLUSIONS: We found several causes of NO deficiencyare associated with hypertension and hypertensive target organdamage in SHR, including decreased nNOS expression,increased ADMA, increased PIN, and increased oxidativestress. The kidney of SHR is less vulnerable to renal injurymight be related to the unaltered ADMA and AAR in thekidney.[Keywords] asymmetric dimethylarginine; nitric oxide; nitric oxidesynthase; hypertension; kidney diseaseFP11-05THE IMMUNE ESCAPE IN RESPIRATORYSYNCYTIAL VIRUS NEPHROPATHY IN RATSAND THE ROLE OF DC-SIGNYannan Guo, Zheng Wang, Jin WuDepartment of Pediatrics, West China 2 nd University Hospital, SichuanUniversity, Chengdu, Sichuan, China, 610041OBJECTIVE: We explored the pathogensis of respiratorysyncytial virus (RSV) nephropathy in rats caused by immuneescape of RSV, which might be mediated by DC-SIGN.METHODS: The mRNA and proteins of RSV G, F andDC-SIGN in kidneys and spleens were assayed by real-timefluorescent quantitative PCR (RT-PCR) and indirect immunefluorescence. By use of ELISA, IL-12 and IL-10 weredetermined, searching for the immunoloregulation ofDC-SIGN in the model. CD 4 and CD 8 in blood were assayedby flowcytometry.RESULTS: In the RSV-inoculated rats, the protein in urineand histopathology of kidney were just as the same as those inminimal change nephrotic syndrome (MCNS). The mRNA ofRSV G, F in kidneys and spleens were persistently expressed( 120d RSV G: ΔCt kidney =4.25±1.94, ΔCt spleen =6.42±1.56;RSV F: ΔCt kidney =10.33±3.25, ΔCt spleen =8.92±1.53), whichaccorded with RSV G and F proteins in indirect immunefluorescence. ⅱ the positively fluorescent luminance ofDC-SIGN in RSV-inoculated rats expressed stronger than thatin the control, and those in kidneys and spleens reached thepeak on day 14. After day 30, the luminance of DC-SIGN wasgradually reduced in the two tissues. The DC-SIGN mRNA inkidneys and spleens on day 4 (ΔCt kidney =11.50±4.30, ΔCt spleen= 13.00±1.70), 14 (ΔCt kidney = 11.40±2.07, ΔCt spleen =12.70±4.06), 60 (ΔCt kidney = 14.10±8.32, ΔCt spleen =14.70±7.13) and 120 (ΔCt kidney = 14.92±1.80, ΔCt spleen =13.75±3.78) was higher, except that in spleens on day 30 (ΔCt=21.90±1.43) was significantly lower than the control (ΔCt=13.67±1.53), P0.05. Compared with the control, IL-12 in renal tissuesincreased in acute stage (from 4d (1205.46±262.07pg/ml) to14d (1054.68±154.18pg/ml)) and decreased after day 30, butthat of IL-10 gradually increased after day 30(120d465.01±80.92 pg/ml). IL-12 in spleens significantly decreased.There was no change in that of IL-10, but a temporal increaseon day 90 (1365.44±188.90 pg/ml).CONCLUSIONS: All above suggested that there be animmune escape of RSV in the RSV nephropathy in rat, inwhich DC-SIGN might play one of important roles.[Keywords]Immune Escape, Respiratory Syncytial Virus, Nephropathy,DC-SIGN108

FP11-06COMPARISON OF EXTENDED VIRULENCEGENOTYPES FOR BACTERIA ISOLATEDFROM PEDIATRIC PATIENTS WITHUROSEPSIS, ACUTE PYELONEPHRITIS, ANDACUTE LOBAR NEPHRONIAChi-Hui Cheng 1 , Lin-Hui Su 2 , Tzou-Yien Lin 3Division of Pediatric Nephrology, Department of Pediatrics, Chang GungChildren’s Hospital, Chang Gung Memorial Hospital1, Department ofLaboratory Medicine, Chang Gung Memorial Hospital2, PediatricInfectious Diseases, Chang Gung Memorial Hospita, Taiwanl 3BACKGROUND: Despite recent advances inmolecular epidemiology and pathogenecity analysesof extraintestinal Escherichia coli infections, detailedanalyses identifying virulence factors of E. coliisolates from pediatric urosepsis patients have notbeen reported. This study was conducted to exploreand differentiate bacterial virulence factorsassociated with urosepsis and two other severeparenchymal infections, acute pyelonephritis (APN)and acute lobar nephronia (ALN), in pediatricpatients.METHODS: Patients included in this study werethose who fulfilled the diagnostic criteria ofurosepsis, APN, and ALN, without underlyingdisease or structural anomalies (excludingvesicoureteral reflux). Patients with cystitis wereincluded as controls. E. coli isolates from urine(cystitis, APN and ALN) or blood (urosepsis)specimens were analyzed using polymerase chainreaction (PCR) for 25 virulence genes.RESULTS: A total of 147 children (24 cystitis, 45APN, 48 ALN, and 30 urosepsis) were enrolled inthe study. Distinct syndrome-specific differences inthe distribution of certain virulence genes, butconservation across syndromes for others, werefound. In addition, urosepsis isolates presentedhigher aggregate virulence factor scores (p < 0.001)compared with APN and ALN isolates, whichshowed similar scores. Cystitis isolates, rather,showed significantly lower aggregate virulencefactor scores (p < 0.001) than all three invasiveurinary bacterial infections; APN, ALN, andurosepsis.CONCLUSIONS: Our findings indicated thaturosepsis isolates carry more virulence factors andare therefore more urovirulent compared with APNand ALN isolates.[Keywords]Acute focal bacterial nephritis; polymerase chainreaction; urosepsis; urovirulence gene; virulence scoreFP12-01DOWN-REGULATION OF ONCOSTATIN M (OSM)PATHWAY IN THE GENESIS OFHYPERCHOLESTEROLEMIA IN THE IL-13OVEREXPRESSION RAT MODEL OF MINIMALCHANGE NEPHROTIC SYNDROME (MCNS)Lauretta D Low 1 , Chan-Yien Chang 1 , Tarun KMaheshwari 1,3 , Henry Yang 2 , Jinmiao Chen 2 , CelinePrakash 2 , Caroline GL Lee 4 , Hui-Kim Yap 1,31 Department of Pediatrics, Yong Loo Lin School of Medicine, National Universityof Singapore; 2 Bioinformatics Lab, Singapore Immunology Network (SIgN)A-Star; 3 Shaw-NKF-NUH Children’s Kidney Centre, University Children’sInstitute, National University Health System, Singapore, 4 Department ofBiochemistry, Yong Loo Lin School of Medicine, National University ofSingaporeOBJECTIVE: We have previously shown that rats overexpressingIL-13 developed a minimal change-like lesion on glomerularhistopathology, accompanied by proteinuria, hypoalbuminemia andhypercholesterolemia. This study aimed to examine the molecularpathways affecting cholesterol metabolism in this model.METHODS: Rats were electroporated every 10 days with plasmidDNA containing rat IL-13 gene for 10 weeks. Serum IL-13, albumin,cholesterol, creatinine and urine albumin were measured serially. RNAwas isolated from liver tissue of 3 control rats, which received onlyplasmid DNA, and 3 IL-13-transfected rats with MCNS whose serumcholesterol levels were >3.10 mmol/L. This was reverse transcribedand hybridized into Illumina Rat Ref12 microarray chips. Preprocesseddata from BeadStudio was normalized by Cross-Correlation method.Differentially expressed genes were selected based on criteria of≥1.75-fold change and coefficient of variance ≤0.6. Gene ontology andpathway analysis were carried out using MetaCore TM .RESULTS: Compared to control rats (n=8), IL-13-transfected rats(n=14) showed significant albuminuria (0.36±0.37 vs 3.45±0.89mg/day, p

FP12-02CAFFEIC ACID PHENETHYL ESTERSUPPRESSES THE INDUCTION OF EOTAXINAND NUCLEAR P-STAT6 IN HUMAN LUNGFIBROBLAST CELLSYu-Ting Lin 1 , Ciao-Jin Chen 2 , Jeng-Yuan Hsu 3 , Jao-JiaChu 4 , Lin-Shien Fu 5Department of Pediatrics, Taichung Veterans General Hospital,Taiwan 1 ,Department of Pediatrics, Taichung Veterans General Hospital,Taiwan 2 , Division of Chest Medicine, Department of Internal Medicine,Taichung Veterans General Hospital, Taiwan 3,4 , Department of Pediatrics,Taichung Veterans General Hospital, Taiwan 5OBJECTIVE: Caffeic acid phenethyl ester (CAPE), anactive component of propolis, has been proven to haveanti-inflammatory and anti-allergic properties. We haveinvestigated the activity of CAPE in regulatingcytokine-induced eotaxin production and its related signalprotein, signal transducer and activator of transcription 6(STAT6), in human lung fibroblast.METHODS: The CCD-11Lu human lung fibroblast cellline was used as an in vitro model. Cells were pretreatedwith CAPE followed by stimulation with interleukin (IL)-4 and tumor necrosis factor alpha (TNF-α). The levels ofeotaxin in cultured supernatants were measured byenzyme-linked immunosorbent assay (ELISA). Thecellular proteins were prepared to nuclear and cytoplasmicprotein extractions .The amounts of STAT6 andphosphorylated STAT6 (p-STAT6), were determined byWestern blot analysis. STAT6 DNA binding activity wasdetected by electrophoretic mobility shift assay (EMSA).MAIN RESULTS: The levels of eotaxin were elevated aftersynergistic stimulation by IL-4 (10ng/mL) and TNF-α(10ng/mL) for 24 hours. The levels of eotaxin secreted bystimulated CCD-11Lu cells were inhibited by pretreatmentwith CAPE at 1μM and 10μM for 3 hours. CAPEpretreatment by 0.1μM and 1μM for 45 minutessuppressed the amount of p-STAT6. CAPE pretreatment by0.01, 0.1, 1, 10μM also inhibited STAT6 DNA nuclearbinding activity.CONCLUSION: CAPE inhibited the production of eotaxinprotein in stimulated human lung fibroblast cells in adose-dependent manner. CAPE also inhibited nuclearp-STAT6 and STAT6 DNA binding activity. We suggestthat CAPE is a promising agent in controlling eotaxinsecretion and subsequent eosinophils influx and maytherefore have a potential role to play in treating allergicairway disease.FP12-03ASSOCIATION BETWEEN FILAGGRINGENE AND ATOPIC DERMATITIS INCHINESE CHILDRENI-Jen Wang 1,2 , Yu-Nian Wu 1 , Wen-Chiuo Wu 1 , Shoei-LoongLin 3 , Pau-Chung Chen 4Department of Pediatrics, Taipei Hospital Department of Health, Taiwan 1 , ChinaMedical Universit, Taiwany 2 , Taipei Hospital Department of Health, Taiwan 3 ,National Taiwan University, Taiwan 4OBJECTIVES: Mutations in the filaggrin gene (FLG)are strong genetic determinants of atopic dermatitis(AD). However, the single nucleotide polymorphism(SNPs) of FLG is not well known for Chinesepopulations. The aim of this study was to evaluate therole of FLG mutations of AD in Chinese.METHODS: We conducted a case control study in 343children aged 2 to 5 years. Subjects were analyzed forthe presence of FLG polymorphism including T454A,P478S, E498D, R501X, H519N, S3247X, R3270C,S3296X, Q3322Q, S2554X, S2889X, and 2282del4 byDNA sequencing. The analyzed mutations were selectedaccording to hot spots of Asian populations on NCBIwebsite and from literature reviews.MAIN RESULTS: The European-specific mutationsR501X and 2282del4 and Japanese -specific mutationsS3296 were absent in Chinese individuals. In contrast, asignificant difference was found in one novel mutationsof P478S genotype frequencies between AD patients andcontrols. After adjusting for potential confounders, thesignificant difference still existed.CONCLUSION: Our results suggest that FLGmutations in Chinese are unique from those found inEuropean people. FLG P478S polymorphism may confersusceptibility to the development of AD among Chinese.[Keywords] filaggrin, atopic dermatitis, polymorphism[Keywords]Caffeic acid phenethyl ester, Eotaxin, STAT6,P-STAT6, Human lung fibroblast cell110

FP12-04SKIN-HOMING STAPHYLOCOCCALSUPERANTIGEN STIMULATED FOXP3+REGULATORY T CELLS EXERT TH2-LIKEFUNCTION IN ATOPIC DERMATITISPATIENTSYu-Tsan Lin, Bor-Luen, ChiangNational Taiwan University Hospital and National Taiwan UniversityCollege of Medicine, TaiwanBACKGROUND: The effect of staphylococcalsuperantigens (SsAgs) on skin regulatory T (Treg)cells of atopic dermatitis (AD) patients is unknown.OBJECTIVE: To compare the effects of SsAgs onthe ratios, functions, and apoptosis of CCR6 + andCCR6 - subtypes of skin-homing Treg cells amongAD patients, patients with respiratory allergy withoutAD, and healthy subjects.METHODS: Using immunofluorescence stainingand flow cytometric analysis, we analyzed PBMCswith or without staphylococcal enterotoxin B (SEB)stimulation in 20 AD patients, 20 asthma/allergicrhinitis (AR) patients, and 20 healthy subjects.RESULTS: SEB decreased the CCR6 + / CCR6 -ratios in skin-homing cutaneouslymphocyte-associated antigen (CLA) + CD4 + Foxp3 +Treg cells from AD patients and increased theCCR6 + / CCR6 - ratios in those from asthma/ARpatients and healthy subjects. SEB inducedproduction of T H 2 cytokine IL-5 in CCR6 - subtypeand anti-inflammatory cytokine IL-10 in CCR6 +subtype of CLA + CD4 + Foxp3 + Treg cells. CLA +CD4 + Foxp3 + Treg cells from AD patients producedmore IL-5 and less IL-10 after SEB stimulation thanthose from healthy subjects. CCR6 - subtype of CLA +CD4 + Foxp3 + Treg cells from AD patients andCCR6 + subtype of those from asthma/AR patientsand healthy subjects were more resistant toSEB-induced caspase-3 activation than the othersubtype. CCR6 - subtype of CLA + CD4 + Foxp3 + Tregcells from AD patients and CCR6 + subtype of thosecells from healthy subjects were more resistant toSEB-induced caspase-3 activation than those fromother subjects.CONCLUSION: Skin-homing Treg cells of ADpatients have a function like effector T H 2 cells afterSsAgs stimulation, which may aggravate allergicskin inflammation.FP12-05THE TRANS-GENETIC EFFECT OF CD14REGULATORY SNPs ON TYPE I INTERFERONPRODUCTION AND GENE EXPRESSIONHong-Hsing Liu 1 , Ming Zheng 1 , David Dill 2 , JianmeiWang 3 , Rosanne Spolski 4 , Warren J. Leonard 4 , Gary Peltz 1Departments of Anesthesia 1 and Computer Science 2 , Stanford University Schoolof Medicine, Stanford, CA 94305, USA; Department of Genes & Genomics,Roche Palo Alto, Palo Alto, CA 94304, USA 3 ; Laboratory of MolecularImmunology, NHLBI, Bethesda, MD 20892, USA 4OBJECTIVES: A data-driven un-biased analysis of globalgene expression in splenic B cells from 11 inbred mouse strainsidentified a gene cluster with 40 type I interferon(IFNα/β)−responsive genes. Because interferons are essentialinflammatory mediators in various diseases, it is important tounderstand the molecular and genetic mechanisms regulatingcoordinated interferon responses to viral and other pathogensin vivo.METHODS: The gene expression pattern in un-stimulatedsplenic B cells purified from 11 inbred mouse strains wereclassified into 40 clusters by k-means clustering. One cluster,which included 40 IFNα/β−responsive genes, was investigatedwith haplotype-based computational genetic mapping andtiered filtering of gene candidates. The predicted geneticeffector was experimentally verified by analysis of purifiedCD11b+ peritoneal macrophages.MAIN RESULTS: This analysis indicated that regulatory SNP(rSNPs) near the Cd14 transcriptional start site could becausative. Subsequent experimental analyses confirmed thatthese rSNPs altered the transcriptional start sites for Cd14mRNA, the basal level of production of soluble CD14 protein,and consequently type I IFN production after poly I:Cstimulation. Exogenous recombinant CD14 effectivelyrestored type I IFN production from peritoneal macrophages ofthe low-CD14 strain.CONCLUSION: Through this novel trans-genetic mechanism,Cd14 rSNPs altered type I interferon production bymacrophages, and the level of expression of at least 40 type Iinterferon responsive genes in B cells. Many of these genesare functionally important mediators of the innate immuneresponse to viral infections. Notably, the inbred strain withlow levels of soluble CD14 production has been used in manyinflammation-related disease models. These findings providenovel insight into the genetic regulation of the innate immuneresponse to viral and other pathogens.[Keywords]Cd14, genome-wide association study, type I interferon[Keywords]Atopic dermatitis, regulatory T cells, Foxp3,cutaneous lymphocyte-associated antigen, CCR6, staphylococcalsuperantigen, TH2 cytokine, apoptosis111

FP12-06REGULATION OF CYTOKINE EXPRESSIONIN HUMAN PLASMACYTOID DENDRITICCELLS BY LABAChih-Hsing Hung, MD 1,2,3,4 , Po-Lin Kuo, PhD 4,6 ,Ching-Hua Huang, MD 5 , Chang-Hung Kuo, MD 3 ,Tai-Heng Chen, MD 3 , Huan-Nan Chen, MS 4 , Shau-KuHuang, PhD 2,4,7 , Yuh-Jyh Jong, MD, PhD 1,2,31 Department of Pediatrics, Faculty of Pediatrics, College of Medicine,Kaohsiung Medical University, Taiwan; 2 Graduate Institute ofMedicine,College of Medicine, Kaohsiung Medical University, Taiwan3 Department of Pediatrics, Kaohsiung Medical University Hospital,Kaohsiung Medical University, Taiwan, 4 Center of Excellence ForEnvironmental Medicine, Kaohsiung Medical University, Taiwan;5 Department of Pediatircs, Yuan’s General Hospital, Kaohsiung; Taiwan;6 Institute of Clinical Medicine, College of Medicine, Kaohsiung MedicalUniversity, Kaohsiung, Taiwan, 7 Johns Hopkins Asthma and AllergyCenter, School of Medicine, Johns Hopkins University, Baltimore, MD21224.OBJECTIVES: Plasmacytoid dendritic cells (pDCs)are critical in controlling adaptive immunity,especially against viral infection with type 1interferon (IFN). The combination inhalers withlong-acting β 2 -agonist (LABA) and inhaledcorticosteroid (ICS) are main therapy for persistentasthma. The major concern with corticosteroids isincreased risk of viral infection. It is not knownwhether LABAs suppress anti-viral cytokineexpression in pDCs.METHODS: Circulating pDCs were magneticallysorted from human PBMCs, and treated with LABAsor a cyclic adeno-monophosphate (cAMP) activatorwith or without addition of Toll-like receptor (TLR)agonists, or a β 2 -adrenoreceptor antagonist,ICI118551. LABAs-associated cytokine responsesand signaling events were examined by ELISA andWestern blotting.MAIN RESULTS: LABAs suppressed CpG (orimiquimod) plus IL-3-induced IFN-α and IFN-βproduction. This effect was reversed by the additionof ICI118551. The cAMP activator conferred asimilar effect as that noted in LABA-treated pDCs.Formoterol also suppressed CpG plus IL-3-inducedERK-MAPK, IRF-7 and IRF-3 expressions. In thepresence of LABA-treated pDCs, T cells showedincreased expression of IFN-γ, but no effect on IL-13or IL-17.CONCLUSION: LABAs suppressed TLR-mediatedtype 1 IFN production via suppressing MAPKs,IRF-7 and IRF-3 in pDCs and also β 2 -adrenoreceptorand cAMP pathway, with subsequent influence onT-cell responses.FP13-01EFFECTS OF HOST INTERLEUKIN-10GENOTYPES ON HBV PRECORE/CORE GENEMUTATION AND ONSET OF SPONTANEOUSHBeAG SEROCONVERSIONJia-Feng Wu, Yen-Hsuan Ni, Huey-Ling Chen, Hong-YuanHsu, Mei-Hwei ChangDepartment of Pediatrics, National Taiwan University Children’s Hospital,TaiwanOBJECTIVES: This study aimed to elucidate the roles ofhost interleukin-10 (IL-10) genotypes on hepatitis B virus(HBV) precore/core gene mutation and spontaneous eantigen (HBeAg) seroconversion.METHODS: Twenty-one chronic HBV infected children80IU/L during follow-up. IL-10 -1082 polymorphism wasdetermined. Serum samples in the tolerance phase(HBeAg[+], anti-HBe[-], ALT80 IU/L with HBeAg[+] weresubjected to HBV viral load and precore/core gene analysis.The HBV precore/core gene mutations immediately beforeHBeAg seroconversion were also determined in the studygroup.MAIN RESULTS: More subjects in the study group carryG1896A (51% vs. 6%; P=0.004), G2304A (36% vs. 9%;P=0.04), HBeAg beta (45% vs. 13%; P=0.02) and delta(20% vs. 3%; P=0.04) epitope mutants than controls at theinflammatory phase with ALT>80 IU/L. The emergence ofG1896A mutation correlated with HBeAg delta epitopemutants (γ, 0.45; P=0.01), while G/G genotype carriers atthe IL-10 -1082 polymorphism site were associated withhigher delta epitope mutation than the A allele carriers(47% vs. 5%; P=0.01). Higher delta epitope mutation wereassociated with lower HBV viral load at inflammatoryphase (γ, -0.47; P=0.01) and shorter interval to finishspontaneous HBeAg seroconversion (regression coefficient,-5.38; P=0.01).CONCLUSION: Subjects with G/G genotype at IL-10-1082 polymorphism is associated with higher HBeAg deltaepitope mutation and lower HBV viral load at inflammatoryphase of chronic HBV infection.[Keywords]Hepatitis B virus, Hepatitis B virus e antigen, Interleukin-10,Seroconversion[Keywords]plasmacytoid dendritic cells, cytokine,long-acting βadrenergic agonist112

FP13-02STIMULATION OF IL-8 ANDBETA-DEFENSIN-2 BYPATHOGEN-ASSOCIATED MOLECULARPATTERNS OF SALMONELLA ENTERICASEROVAR TYPHIMURIUM IN POLARISEDHUMAN INTESTINAL EPITHELIAL CELLSShiuh-Bin Fang 1 , Mark Lucas 1 , Duncan J. Maskell 2 ,Alan D. Phillips 1Centre for Paediatric Gastroenterology, Royal Free Campus, UniversityCollege London Medical School, London, UK 1 , Department of VeterinaryMedicine, University of Cambridge, Cambridge, UK 2OBJECTIVES: The aim of this study was to investigate whichpathogen-associated molecular patterns (PAMPs) of Salmonellaenterica serovar Typhimurium (S. Typhimurium) stimulateepithelial IL-8 and β-defensin-2 (hBD-2) mRNA expression andprotein secretion in human intestinal epithelial cells.METHODS: Polarised 14-day-old Caco-2 cells grown ontranswells were stimulated with apical and/or basolateralapplication of three Salmonella PAMPs for 2 hours(lipopolysaccharide [LPS, 10 µg/ml], flagellin [FliC, 2 µg/ml] orS. Typhimurium SL1344 DNA [25 µg/ml]). Monolayers were alsoapically infected with S. Typhimurium strains for 2 hours(wild-type SL1344, invasion-incompetent SPI-1 mutant ∆spaS,and FliC-deficient mutant ∆fliM) at a multiplicity of infection of20:1 before infections were stopped with 1-hour gentamicintreatment (100 µg/ml). At 7 hours post infection IL-8 and hBD-2mRNA expression were measured using quantitative real-timePCR; at 21 hours post infection basolateral and apical supernatantswere respectively collected to measure protein levels of IL-8 andhBD-2 using ELISA. Statistical significance (P

FP13-04TUMOR NECROSIS FACTOR-ALPHAPROMOTER REGION POLYMORPHISMSAFFECT THE COURSE OF HEPATITIS BVIRUS INFECTIONPeichi Kao 1 , Jia-Feng Wu 1 , Yen-Hsuan Ni 1 , Ying-TingLin 1 , Huey-Ling Chen 1 , Sandy Huey-Jen Hsu 2 ,Hong-Yuan Hsu 1 , Mei-Hwei Chang 11Department of Pediatrics, National Taiwan University Hospital, Taipei,Taiwan; 2Department of Laboratory Medicine, National Taiwan UniversityHospital, Taipei, TaiwanOBJECTIVES: This study aimed to investigate theroles of tumor necrosis factor-α (TNF-α) genepolymorphisms on hepatitis B virus (HBV) clearance.METHODS: This cross-sectional study evaluated thegenetic polymorphism in TNF-α (-1031 T to C, -863 Cto A, -857 C to T, -308 G to A, and -238 G to Atransition) gene in 274 chronic HBV infected patientsand 194 patients with resolved HBV infection. Theperipheral blood mononuclear cells (PBMC) isolatedfrom 77 of the 274 (28%) patients who have chronicHBV infection with negative HBV e antigen andpositive anti-HBe were stimulated with HBV coreantigen (HBcAg). Data on TNF-α genotypes andphenotypes in subjects with/without the A allele at theTNF-α -863 promoter SNP (rs1800630) werecompared.MAIN RESULTS: The A allele in the -863 promoterregion of TNF-α gene was present in 154 (56.2%)chronic HBV infected patients and 87 (44.8%) patientswho recovered from HBV [Odd’s ratio (OR), 1.58; p

FP13-06INDUCIBLE PLURIPOTENT STEM CELLSPROTECT MICE FROM DEXTRAN SODIUMSULFATE-INDUCED COLITISChing-Feng Huang 1 , Shin-Nan Chian 1 , Wen-Tsung Lo 1 ,Shih-Hwa Chiou 21 Department of Pediatrics, Tri-Service General Hospital, National DefenseMedical Center, Taipei, Taiwan, Republic of China; 2 Department of MedicalResearch & Education, Taipei Veterans General Hospital, Taipei, Taiwan,Republic of ChinaOBJECTIVE: The inflammatory bowel diseases resultfrom a chronic inflammatory response ofgastrointestinal tract, leading to intestinal damage.Intake of dextran sodium sulfate (DSS) in experimentalmice had been proved to induce intestinal inflammationthat mimics inflammatory bowel disease. Induciblepluripotent stem (iPS) cell is a novel stem cellpopulation induced from murine fibroblasts bytransduction of four transcription factors. Stem cells areable to differentiate into many types of cells andconsidered as a restorative cell therapy for thetreatment of various diseases. We investigated whetheriPS cells injection could protect mice againstDSS-induced colitis.METHODS: C57BL/6 mice were treated for 7 dayswith 4% DSS in the drinking water to induce colitis.Inducible pluripotent stem cells or vehicle wereinjected from tail vein at the third day since DSSintake. Control mice were similarly treated with PBSonly. Disease activity was recorded on a daily basis foreach animal including changes in body weight, stoolconsistency, anal prolapse and bloody feces. Intestinelength was also measured 3 days after cease of DSStreatment.MAIN RESULTS: After administration of DSS, micefrom both groups receiving DSS treatment revealedloss of body weight, increasing incidence of diarrhea,bloody feces and anal prolapse and shortening of colonlength. However, the mice receiving iPS cell injectionsignificantly reduced disease activity including lessbody weight loss and recovery from diarrhea, bloodystool and anal prolapse. Those drank DSS without iPScells injection had significant shortening of colonlength than the control mice.CONCLUSION: These findings support the iPS cellsattenuated the intestinal damage induced by DSS andmay have therapeutic value for inflammatory boweldisease. The histological finding and intestinal cytokineprofile are under investigation.FP14-01DECOY RECEPTOR 3 (DCR3) AMELIORATESEXPERIMENTAL AUTOIMMUNEENCEPHALOMYELITIS (EAE) - BY DIRECTLYCOUNTERACTING LOCAL INFLAMMATIONAND DOWNREGULATING TH17 CELLSShyi-Jou Chen 1 , Yen-Lin Wang 2 , Wen-Tsung Lo 3 ,Chih-Chien Wang 4 , Pao-Luh Tao 5 , Huey-Kang Sytwu 6Department of Pediatrics, Tri-Service General Hospital, National DefenseMedical Center 1 , Graduate Institute of Life Sciences, National defense medicalcenter 2 , Department of Pediatrics, Tri-Service General Hospital, NationalDefense Medical Center 3 , Department of Pediatrics, Tri-Service GeneralHospital, National Defense Medical Center 4 , Pharmacology, National defenseMedical Center 5 , Graduate Institute of Medical Sciences, National DefenseMedical Center 6 (Taiwan)To investigate the therapeutic potential of decoy receptor3 (DcR3) in multiple sclerosis (MS), we used intrathecal(IT) administration of DcR3 into C57/BL6 mice withexperimental autoimmune encephalomyelitis (EAE).DcR3 significantly ameliorated EAE symptoms asshown by a lower clinical score and less inflammation inthe spinal cord. The expression of TNF-α, IFN-γ, andIL-17 was lower in the spinal cord in IT DcR3-treatedmice. Flow cytometry showed a drastic reduction inIL-17-producing CD4 T cells, slightly fewer IFN-γproducing CD4 T cells and more IL-4-producing CD4 Tcells isolated from the central nervous system (CNS) ofIT DcR3-treated mice than of controls. Myelinoligodendrocyte glycoprotein (MOG)-specific T cellproliferation was significantly inhibited in DcR3-treatedmice. The IL-17 concentration was lower and the IL-4concentration higher in the supernatants ofMOG-stimulated splenocytes from DcR3-treated mice.An adoptive transfer study showed that splenocytes fromDcR3-treated mice retained this disease-inhibitingability. Our data suggest that DcR3 has potential as asuppressor of CNS inflammation in EAE, which may beattributed to either direct inhibition of CNSinflammation or suppression of encephalitogenic Th17cells. In conclusion, we demonstrate a therapeutic effectof DcR3 in EAE, suggesting its potential for treatinghuman MS. (accepted in Mol. Immunol.)[Keywords]Experimental autoimmune encephalomyelitis (EAE);Multiple sclerosis (MS); Decoy receptor 3 (DcR3); Myelinoligodendrocyte glycoprotein (MOG); Th1; Th2; Th17[Keywords]colitis, inducible pluripotent stem cells, dextran sodiumsulfate, mice115

FP14-02GENERATION OF SKELETAL MUSCLESTEM/PROGENITOR CELLS FROM MURINEINDUCED PLURIPOTENT STEM CELLSHsi Chang, a Yuta Mizuno, a Tatsutoshi Nakahata, a,b andToshio Heike aaDepartment of Pediatrics, Graduate School of Medicine, GraduateSchool of Medicine,Kyoto University; Mitsubusi Kyoto Hospital, 606-8507,Japan; bCenter for iPS Cell Research and Application, iCeMS, KyotoUniversity, Kyoto, 606-8507, JapanInduced pluripotent stem (iPS) cells, which are a typeof pluripotent stem cell generated from reprogrammedsomatic cells, are expected to have potential forpatient-oriented disease investigation, drug screening,toxicity tests, and transplantation therapies. Here, wedemonstrated that by using the induction system whichwe reported (Chang et al. FASEBJ. 2009;23:1907-1919), the murine iPS cells indicated thepotential to develop in vitro into skeletal musclestem/progenitor cells, which are almost equivalent tomurine embryonic stem cells. These murine iPSderived cells expressed of strong in vitro myogenicpotential and could be effectively enriched byfluorescence-activated cell sorting using theanti-satellite cell antibody SM/C-2.6. Furthermore,upon transplantation into mdx mice, a well knownmodel mouse of Duchene muscular dystrophy (DMD),these iPS derived SM/C-2.6 + cells exerted sustainedmyogenic lineage differentiation in injured muscles,while providing long-lived muscle stem cell support.Our data suggest that iPS cells have the potential to beused in clinical treatment of muscular dystrophies.[Keywords]Duchene muscular dystrophy, induced pluripotent stemcells, Pax7, long-term engraftment, no teratoma formation, highengraftment efficiencyFP14-03EPIDEMIOLOGY OF CHILD ABUSE REPORTEDFROM THE SOCIAL WELFARE REPORTSYSTEM IN A TERTIARY MEDICAL CENTER INTAIWANJiun-Chang Lee, MD 1,2 , Kuang-Lin Lin, MD 1 , Huei-ShyongWang, MD 1 , Min-Liang Chou, MD 1 , Po-Cheng Hung, MD 1 ,Meng-Ying Hsieh, MD 1 , Jainn-Jim Lin, MD 1,2 , Shao-HsuanHsia, MD 2 , Chang-Teng Wu, MD 2Division of Pediatric Neurology 1 ; Division of Pediatric Critical and EmergencyMedicine 2 , Chang Gung Children’s Hospital and Chang Gung MemorialHospital, Chang Gung University College of Medicine, Taoyuan, TaiwanOBJECTIVE: The purpose of this study was to present theepidemiology of child abuse among children younger than 17years of age child abuse reported from the social welfarereporting system in a tertiary medical center in Taiwan. Thisstudy focused on obtaining great detail information on childabuse occurring within a fixed population.METHODS: Child abuse is a well known cause of morbidityand mortality in children. In Taiwan, little information has beenpublished regarding the status of child abuse. To provide moreinformation on child abuse for the purpose of child abuseprevention, a retrospective study was designed and conductedto analyze the reported child abuse cases from the socialwelfare reporting system in a tertiary medical center in Taiwan.All chart reviews concerning child abuse in those under 17years of age, reported from the social welfare reporting systemin our hospital from September 2001 through May 2009, wereincluded in this study. The ages, sexes, regions of residence,notification departments, related personnel, risk factors, injurytypes and clinical outcomes of those chart reviews were thenanalyzed.MAIN RESULTS: A total of 844 reported cases concerningchild protection were recorded. 203 of those were categorizedinto child abuse and other 641 cases were categorized intochild neglect. About the child abuse group, Males were moreprevalent than females (61% vs. 39%) Most child abuse cases(62%) were under the 3 years old (

FP14-04ZINC CONCENTRATION IN SERUM ANDCEREBROSPINAL FLUID SIMULTANEOUSLYDECREASE IN CHILDREN WITH FEBRILESEIZURE: FINDINGS FROM A PROSPECTIVESTUDY IN BANGLADESHMd Abid Hossain Mollah 1 , Sudesh Chandra Rakshit 1 ,Kazi Selim Anwar 2 , M Iqbal Arslan 3 , Narayan Saha 11 Department of Paediatrics, Dhaka Medical College & Hospital, Bangladesh;2 Department of Microbiology, Institute of Public Health, Dhaka, Bangladesh;3 Department of Biochemistry, BSMMU, Dhaka, BangladeshOBJECTIVES: Since the underlying mechanisms offebrile seizure (FS) having multi-factorial aetiology yetremains unclear, we conducted this prospectivelydesigned cross sectional study to determine if there wasany simultaneous change in zinc (Zn) concentration inserum and cerebrospinal fluid (CSF) among the FSchildren in comparison to their matched non-seizurefebrile (NSF) peers.METHODS: Zn concentration (level) in both serum(intravenous blood) and CSF (lumber puncture: LP) of50 children with FS and 30 NSF peers (serving ascontrols) were measured employing graphite furnaceatomic absorbance spectrophotometer. Data wereanalyzed to compare Zn level between 2 groups usingappropriate statistical tools employing SPSS/Windows12.0.RESULTS: Mean Zn conc. in both serum and CSF wasless in FS children (464.60 ± 64.57 µg/L and 46.28 ±7.46 µg/L , respectively) than their matched NSF peers(749.33 ± 73.19 µg/L and 111.28 ± 19.11 µg/L,respectively) showing significant differences both inserum (p

FP14-06THE ANALYSIS OF DISTRIBUTIONCHARACTERISTICS OF SPIKE WAVE IN WESTSYNDROME’S EEGLuo Rong, Cai xiaotang, Gan jingWest China Second University Hospital, Sichuan University, ChinaFP15-01PEDIATRIC RESIDENT MANPOWER INTAIWANTsuen-Chiuan TsaiGraduate Institute of Healthcare Administration, I-Shou UniversityDepartment of Pediatrics, E-Da Hospital (Taiwan)PURPOSE: The EEG of infantile spasms almostshowed left-right asymmetry, multi-focal or partialcontinued discharge. We analyzed distributioncharacteristics of EEG spike-wave of different types ofinfantile spasms.METHOD: Video-EEG monitoring in children withinfantile spasms were calculated, and each lead of thespike-wave density and relative spike density werecalculated. Causes of the disease were examinated inall patients.RESULT: There were 33 patients with symptomaticinfantile spasms, 75.7% mainly discharged inparieto-occipital areas, 66.6% discharged significantlyin the temporal areas, particularly the post-temporal;There were nine cases of cryptogenic infantile spasms,44.4% mainly discharged in parieto-occipital areas,55.5% mainly discharged in temporal areas. Insymptomatic infantile spasms, 69.7% had perinatalcauses, 82.6% mainly discharged in parieto-occipitalareas, 73.9% mainly aggregated in the temporal areas,particularly the post-temporal.CONCLUSION: The symptomatic infantile spasmscompared with cryptogenic infantile spasms morelikely to appear atypical EEG changes, especiallydischarges in parieto-occipital areas and temporaldischarge, which may be associated with local damageand brain development of the cortex.[Keywords]infantile spasms;EEG;spike waveBACKGROUND: Maldistribution of physicianmanpower in Taiwan, both geographically and inspecialty, has been reported. It was believed Pediatricswas the one in short manpower supply. Beginning in2000, the Taiwanese birth rate has dropped to the lowestlevel of the world (7.3 per 1,000 persons in 2008). Thesize of Pediatric resident enrollment dropped even more,and the resident manpower became low far behind theneed. It was not known about the severity of theshortage, and the solutions for the problem.OBJECTIVE: This study is to study the demand ofPediatric residents in the training centers in Taiwan; toexplore the possible solutions for the shortage ofPediatrician manpower.METHODOLOGY: A written questionnaire wasdistributed to all the Pediatric Resident Training centersto ask for demand of resident size for now and the future5 years, and to determine the gaps between current statusand needs. The service volume of bed, out-patient andin-patient number were also asked. This study alsoreviewed the solutions reported by Taiwan PediatricAssociation Board Committee.RESULTS: Among the 86 hospitals that were granted asa Pediatric training program, 69 responded. There were20 hospitals (23.3%) did not have any resident, and 75(87%) hospitals have resident size less than 3. In 2009,there were only 128 first year residents in total, whichaccounted for 58.2% of the demand number. Thereported solutions included the recruitment of NursingPractitioners in Pediatrics, the establishment ofcollaborator programs with Internal Medicine,Emergency, and Family Medicine.CONCLUSION: The shortage of Pediatric Residentmanpower was significant nowadays. The solutions tocompensate the manpower shortage have to beestablished as soon as possible to ensure the healthcarequality for children.118

FP15-02PEDIATRICIANS’ ROLE OF CARINGPRESCHOOL CHILDREN IN TAIWAN UNDERTHE NATIONAL HEALTHMing-Chih LinPediatric department, Taichung Veterans General Hospital, TaiwanBACKGROUND: The National Health Insurance(NHI) covers more than 98% of the 22 million peoplein Taiwan. Because referral is not mandated,competition among specialties exists in caringpreschool children. The aim of this study was toanalyze the utility of outpatient service amongpreschool children to investigate the pediatricians’ rolein caring preschool children. We also analyzed how thedensity of specialists induces demand by using the NHIdatabase.METHODS: We used the systematic sampling file,CD20040, from the bureau of NHI, Taiwan, as the datasource for analysis. We linked the file to the registriesfor medical personnel and the board-certifiedspecialists to analyze the specialty distribution. We alsolinked to the registry for contracted medical facilities toanalyze the distribution in different levels of hospitals.RESULTS: In total, 56,144 outpatient visits forpreschool children were analyzed. Among them, 59.1%of outpatient services for preschool children wereprovided by pediatric specialists, 20.7% byotolaryngologists, 13.5% by family medicinespecialists, and the other 6.7% by general practitioners.Most of the visits occurred in the primary care setting(84.1%). As children grew older, a significant declinein the pediatric specialists’ visit rate and an increase inthe otolaryngologists’ visit rate were observed in theprimary care setting. Young children visited pediatricspecialists more frequently. The pediatric specialists’visit rate was higher in the northern urban areas. It wasalso significantly correlated with the density ofpediatricians.CONCLUSION: In summary, otolaryngologistscompete with pediatricians in the primary care ofpreschool children in Taiwan. The proportion of visitsto pediatric specialists was significantly correlated withthe density of pediatricians among different counties.The NHI should modify its policy to make the medicalsystem more equitable.FP15-03SMOKING BEHAVIOR AMONG ADOLESCENTSIN THAILAND AND MALAYSIA: RESULTSFROM INTERNATIONAL TOBACCO CONTROLPOLICY-SOUTH EAST ASIA.Tawima Sirirassamee, MD. 1 , Buppha Sirirassamee, Ph.D. 2 ,Ron Borland, Ph.D. 3 Geoffrey T Fong, Ph.D. 4 .Srinakarinwirot University 1 , Institute for Population and Social Research 2 , TheCancer Council Victoria 3 , University of Waterloo 4 (Thailand)OBJECTIVE: To compare the smoking behavioramong adolescents in Thailand and Malaysia.METHODS: A population-based, national surveys wereconducted among 1,694 adolescents with ages between13 and 18 from Thailand (n=917) and Malaysia (n=777). Respondents were selected using multistage clustersampling. Respondents were asked to completeself-administered questionnaires. Data were analyzedusing descriptive statistics, Chi-Square tests and t tests.MAIN RESULTS: Approximately 5 percents of Thaiand Malaysian adolescents were current smokers, withan additional 9.6 percents of Thai and 7.8 percents ofMalaysian adolescents reported being a beginner smoker.On average, Thai smoker reported to have first smoked awhole cigarette at 14.6 years of age (SD= 1.93), whileMalaysian smoker at age 13.9 (SD= 2.16). About half ofThai smoker (56.9%) reported that they bought cigarettesfor themselves and 31.5 percents got cigarettes fromfriends. In Malaysia, most of smoker (71.4%) reportedthat they bought cigarettes for themselves, only 19.8percents got cigarettes from friends. Sixty seven percentsof Thai adolescent smokers smoked factory-madecigarettes as their usual brand compare to 29.9 percentsof Malaysian adolescent smokers. Eight percents of Thaiadolescents and 13.6 percent Malaysian adolescentsreported smoking hand-rolled cigarettes. Eighty fourpercents of Thai and 76.1 percent of Malaysianadolescent smokers reported that they tried to quit.CONCLUSION: Smoking prevalence of Thaiadolescents was closed to that of Malaysian adolescents.Factory-made cigarette consumption is an importantproblem in Thai adolescents and needs to be targeted.[Keywords]Adolescents, Smoking[Keywords]Health manpower, preschool children, specialists119

FP15-04ASSOCIATION BETWEEN BIRTH WEIGHT,ADULT BODY MASS INDEX, HEIGHT, ANDOTHER FACTORS IN POSTMENOPAUSALWOMENOwen TienYu Yang 1 , Benjamin J. Cairns 1 and ValerieBeral 1 , on behalf of the Million Women StudyCollaborators1 Cancer Epidemiology Unit, University of Oxford, United KingdomOBJECTIVE: Although birth weight is known topredict weight and height in adulthood, the relationshipbetween birth weight and other adult characteristics isless clear. This study examines the associationsbetween birth weight, adult body size and other factorsamong postmenopausal women.METHODS: The Million Women Study is a largepopulation-based prospective cohort study ofmiddle-aged women in the UK, recruited through theNational Breast Screening Programme between 1996and 2001. This analysis is based on 314,513 womenwho were postmenopausal when they reported theirbirth weight.RESULTS: The relationship between birth weight andadult body mass index (BMI) was U-shaped. Forexample, the percentage of obesity (BMI>30 kg/m 2 ) inadulthood among women with low birth weight(4.0kg) (p

FP15-06EFFECTS OF COMMUNITY-BASED FOLLOW-UP CARE,WITH OR WITHOUT FOOD SUPPLEMENTATION AND/ORPSYCHOSOCIAL STIMULATION, ON THE RECOVERYOFSEVERELY UNDERWEIGHT CHILDREN: A RANDOMIZEDINTERVENTION TRIALMd Iqbal Hossain 1,2 , Baitun Nahar 1,3 , J D Hamadani 1 ,TahmeedAhmed 1 , Kenneth H Brown 2,41 International Centre for Diarrhoeal Disease Research, Bangladesh;2 Department of Nutrition and Program in International and CommunityNutrition, University of California, Davis, USA; 3 Institute of Mother and ChildHealth, Uppsala University,Sweden; 4 Helen Keller International, Dakar,SenegalFP16-01CONGENITAL GENERALIZEDLIPODYSTROPHY WITH MUSCULARDYSTROPHY CAUSED BY NOVEL PTRFMUTATIONEry Kus Dwianingsih, Yasuhiro Takeshima, Mariko Yagi,Hiroyuki Awano, Rusdy Ghazali Malueka, Kyoko Itoh*,Masafumi MatsuoDepartment of Pediatrics, Kobe University Graduate School of Medicine, Kobe,Japan; Department of Pathology and Applied Neurobiology, Graduate School ofMedical Science Kyoto Prefectural University of Medicine, Kyoto, Japan*BACKGROUND/OBJECTIVE: Malnutrition heavily contributesto child morbidity and mortality, impaired mental development, andloss in national productivity in low-income countries includingBangladesh. Improved regimens are needed for the treatment ofseverely malnourished children. The study was done to assess theeffects of community-based follow-up care, with/without foodsupplementation and/or psychosocial stimulation, as alternatives tohospital-based follow-up of children previously hospitalized fortreatment of diarrhea and severe underweight.DESIGN: 507 severely underweight (WAZ

FP16-02MODULATION OF TRANSIENT RECEPTORPOTENTIAL,4 (TRPV4)Hueng-Chuen Fan 1,2 , Xu-Ming Zhang 2 , Jou-Shyi Chen 1 ,Chih-Chien Wang 1 , Peter A McNaughton 2Department of Pediatrics, Tri-Service General Hospital and National DefenseMedical Center, Taipei 11490 1 , Department of Pharmacology, University ofCambridge, Cambridge CB2 1PD, United Kingdom 2OBJECTIVES: The modulation of nociceptors by inflammatorymediators lies at the core of understanding peripheralsensitization. TRPV4, a member of the transient receptor familyof ion channels, is thought to be a transducer of noxioushypo-osmotic and mechanical stimuli. It is interesting thatcombined action of multiple inflammatory mediators mayactivate TRPV4. This prompted us to hypothesize thatinflammatory mediators can posttranslationally modify TRPV4or increase TRPV4 protein expression to produce mechanicalsensitization. In the present study, the role of TRPV4 inmechanical hyperalgesia induced by inflammatory mediators, thesecond-messenger pathways and the scaffoid protein wasinvestigated in detail.METHODS: HEK293 cells, which were reported to lackTRPV4 this channel, were grown in DMEM containing serum,L-glutamine, penicillin and streptomycin at 37°. After transientlytransfected with the human TRPV4 plasmid, cells were mountedin a perfusion chamber on a confocal microscope stage. Calciumimaging of there cells was performed with PKC and PKAagonists and inhibitors, and AKAP79 overexpression and geneticknockdown against this scaffoid protein were all investigatedMAIN RESULTS: The sensitization of TRPV4 was greatlyenhanced after exposure to the PKC activator phorbol12-myristate 13-acetate (PMA) and cAMP activator forskolin(FSK). The phosphorylation level of TRPV4 was greatlyenhanced with PMA treatment. Functional studies using calciumimaging showed that AKAP79 overexpression enchancedsensitization of TRPV4 by FSK and PMA, while downregulationof AKAP79 using siRNA inhibited sensitization. TRPV4coexpression with AKAP79 enhanced the phosphorylationinduced by PMA, and the phosphorylation level significantlydecreased in cells coexpressing TRPV4 and siRNA AKAP79.CONCLUSION: In conclusion, AKAP79 may orchestrate PKCand PKA by tethering these distinct signalling molecules, toenhance the function of and phosphorylation level of targetingproteins. Manipulating this signalling integrator could be apromising way for developing analgesics.[Keywords] TRPV4: transient receptor potential vanilloid 4, PMA: phorbol12-myristate 13-acetate, PKC: protein kinase C,FSK: forskolin, PKA :cyclicAMP-dependent protein kinase, AKAP:a kinase-anchoring proteinFP16-03CHARACTERIZATION OF EMD -/- /LMNA H222P/H222PMICEWen-Chen Liang 1,2 , Yukiko K. Hayashi 2 , Young-Eun Park 2 ,Hiroaki Mitsuhashi 2 , Takuro Arimura 3 , Gisèle Bonne 4 ,Satoru Noguchi 2 , Ichizo Nishino 21 Department of Pediatrics, Kaohsiung Medical University Hospital, KaohsiungMedical University, Kaohsiung, Taiwan; 2 Department of NeuromuscularResearch, National Institute of Neuroscience, National Center of Neurology andPsychiatry, Tokyo, Japan, 3 Department of Molecular Pathogenesis, MedicalResearch Institute, Tokyo Medical and Dental University, Tokyo Japan, 4 Inserm,U582, Institut de Myologie, Paris, FranceOBJECTIVE: Emery-Dreifuss muscular dystrophy (EDMD)is a genetically heterogeneous neuromuscular disordercharacterized by early-onset contractures, progressiveweakness in humeroperoneal muscles, and cardiomyopathywith conduction block. To date, mutations in four genes,LMNA, EMD, SYNE-1 and SYNE-2, have been identified tocause EDMD. All these genes encode nuclear membraneproteins of A-type lamin, emerin, nesprin-1 and nesprin-2,respectively. Several knockout or mutant mouse models havebeen developed to explore the disease pathomechanism. Inorder to elucidate the function of emerin interacting withmutant A-type lamin, we crossed Lmna H222P/H222P with Emd -/-mice to produce and characterize double mutant mice(Emd -/- /Lmna H222P/H222P ).METHODS: We recorded the body weight, life span, grossfeatures and analyzed the pathology of skeletal and cardiacmuscles in wild-type, Emd -/- , Lmna H222P/H222P mutant andEmd -/- /Lmna H222P/H222P double mutant mice. Compared towild-type mice, double mutant mice showed reduced lifeexpectancy, similar to Lmna H222P/H222P mice.RESULTS: From 15 weeks of age, gradual loss of bodyweight accompanied with muscle weakness and kyphosis wereprominent compared to Lmna H222P/H222P mice. Myoathicfeatures of skeletal muscle including fiber size variation andincreased number of internalized nuclei were also remarkable.Interestingly, double mutant mice did not show obvious signsof cardiac failure including enlarged heart, pericardial andpleural effusion. Pathology of cardiac muscle displayed smallerfiber size with no marked fibrosis.CONCLUSION: Our results indicate that emerin may playdifferent roles in the pathomechanism of cardiac and skeletalmuscles via the interaction with mutant A-type lamin. Furtherfunctional analyses are needed to clarify the intertalks betweenemerin, A-type lamin and other nuclear membrane proteins innuclear envelopathy.[Keywords]Emery-Dreifuss muscular dystrophy, Lamin A/C, Emerin122

FP16-04UBIQUITIN CARBOXYL-TERMINAL ESTERASE L1(UCHL1) REGULATES THE LEVEL OF SMNEXPRESSION THROUGH UBIQUITINATION INPRIMARY SPINAL MUSCULAR ATROPHYFIBROBLASTSTai-Heng Chen 1,2,3 , Shih-Hsien Hsu 2 , Tze-Kiong Er 2,4 ,Yuh-Jyh Jong 1,2,41 Department of Pediatrics, Kaohsiung Medical University Hospital,Kaohsiung Medical University, Kaohsiung, Taiwan; 2 Graduate Institute ofMedicine, College of Medicine, Kaohsiung Medical University, Kaohsiung,Taiwan; 3 Division of Pediatric Emergency, Department of Emergency,Kaohsiung Medical University Hospital, Kaohsiung Medical University,Kaohsiung, Taiwan; 4 Department of Laboratory Medicine, Kaohsiung MedicalUniversity Hospital, Kaohsiung, TaiwanOBJECTIVE: Spinal muscular atrophy (SMA), a hereditaryneurodegenerative disease caused by homozygous deletion ormutation in the survival of motor neuron 1 (SMN1) gene, is theleading genetic cause of infant mortality. Its severity directlycorrelates to the expression level of SMN protein in SMApatients, but the regulatory mechanisms of SMN proteinexpression remain incompletely defined. In 2004, we firstproposed that SMN protein degradation might be regulated by aproteasome ubiquitination system and thereafter there are severalstudies in recent years which have also shown similar results. Inthis study, we aim to identify candidate proteins in modulatingthe level of SMN proteins probably through the mechanisminvolving ubiqutination, resulting in degradation of SMNproteins.METHODS: Proteomics combining two-dimensional (2D)electrophoresis and HPLC-MS/MS were performed in proteinextracted from 3 type I SMA patients and 3 normal skinfibroblast cells. Thereafter ubiquitin carboxyl-terminal esteraseL1 (UCHL1) was identified as candidate protein in regulation ofSMN protein functions. Subsequently, immunoprecipitation andimmunofluorecence assays in p19 and NSC34 cells wereperformed to determinate the interactions between UCHL1 andSMN protein. Over-expression of UCHL1 with constructs taggedwith RGS-6His and inhibition of UCHL1 by using UCHL1inhibitor (LDN57444) and knock-down approach, shRNAi, werealso applied to monitor the regulatory effects of UCHL1 on SMNprotein.MAIN RESULTS: Our initial proteomics analysis discoveredsignificant up regulation of UCHL1 in type I SMA fibroblastswhen compared to normal fibroblasts. Over-expression ofUCHL1 in p19 and NSC34 cells significantly reduced the levelof SMN proteins in vivo, and, in fact, purified UCHL1 wasshown to be able to enhance, in a dose-dependent manner, thelevel of ubiquitinated SMN in vitro. Further, inhibition ofUCHL1 activity by UCHL1 inhibitor (LDN57444) increasedcellular SMN protein and gems number in the nucleus in NSC34and SMA skin fibroblast cells.CONCLUSIONS: Our results suggest that UCHL1, an ubiquitinligase, might be a critical regulator in controlling cellular SMNprotein turnover. Therefore, development of strategies to inhibitthe level and/or activity of UCHL1 could serve as possibletherapeutic benefit for SMA patients through their augmentingeffect on SMN protein levels.FP16-05REVERSAL OF SYNAPTIC PLASTICITYDEFICIT IN A MOUSE MODEL OF RETTSYNDROME BY APPLYING NMDA RECEPTORANTAGONISTShih-Ming Weng 1,2 , Mark Bailey 1 , Stuart Cobb 1Institute of Biomedical & Life Science, University of Glasgow, UK 1 &Department of Pediatrics, Wan-Fang Hospital, Taipei, Taiwan 2OBJECTIVES: Rett syndrome (RTT) is a pediatricneurodevelopmental disorder with a delayed onset ofsymptoms and is a leading cause of severe mental retardationin girls. RTT is mainly originated from mutations in theX-linked gene MECP2 and mutations at this locus are alsofound in patients with other neurological conditions includingmilder forms of learning disability, autism and X-linked mentalretardation. Due to its monogenic nature, RTT has been thefocus of intense investigation with the hope that understandingsynaptic and structural plasticity deficits in RTT might provideinsights into the pathophysiology of autism spectrum disordersmore generally. Recent laboratory studies have shown synapticplasticity deficit in RTT mice, however, no therapeuticapproach is proved effective to reverse it pharmacologically.The aim of current study was to assess synaptic plasticity inRTT mice by examining long-term potentiation saturationeffect and attempt to reverse it by applying medications.METHODS: Mecp2 was silenced in mice through targeting ofa stop cassette. Mice developed the features of RTT includinghypoactivity, gait abnormalities, and breathing dysrhythmiasgradually during development. After hemizygous mice becameovertly symptomatic, both mutant and wild-type littermateswere sacrificed and brains were transferred to ice-coldoxygenated artificial cerebrospinal fluid. Parasaggitalhippocampal slices were prepared and transferred to aninterface-type tissue chamber for at least one hour to allowequilibrate. Standard extracellular recording was used tomonitor field excitatory potentials and long-term potentiationin stratum radiatum of area CA1.MAIN RESULTS: Our data showed that hemizygous micedisplayed deficits in short and long term forms of hippocampalsynaptic plasticity. Plasticity deficits were consistent with asaturation of long-term potentiation (a ceiling effect) and couldbe reversed pharmacologically after applying NMDA receptorantagonist.CONCLUSION: These data suggest that synaptic functionaldefect is the key feature in the Rett brain but that the deficitmay be amenable to future pharmacological interventions.[Keywords]Rett syndrome, NMDA receptor, MECP2, synapticplasticity[Keywords]SMA, UCHL1, SMN and Ubiquitination123

FP16-06SUMATRIPTAN AS A TREATMENT FORCYCLIC VOMITING SYNDROMEToshiyuki Hikita 1 , Hiroko Kodama 1 , Kaori Ogita 1 , KaoriAmakata 1 , Natsue Nakamoto 1 , Sono Kaneko 1 , FumiayaKaga 1 , Yasushi Fujii 1 , Yukishige Yanagawa 1Department of Pediatrics, Teikyo University School of Medicine, Japan 1FP16-07DETERMINATION OF BRAIN DEATH INCHILDREN WORLDWIDEKun-Long Hung1 and the Study Group on the Criteria forDetermination of Brain Death in Children of Taiwan ChildNeurology Society, Taiwan1 Department of Pediatrics,Cathay General Hospital, Taipei, TaiwanOBJECTIVES: The aim of this study was to evaluate the use ofsumatriptan for cyclic vomiting syndrome (CVS) in children andadults.METHODS: After obtaining informed consent, 12 patients (11children and 1 adult), who were referred to Teikyo UniversityHospital and diagnosed with severe CVS by pediatricneurologists, were enrolled in this trial. All patients werediagnosed with CVS based on the International HeadacheClassification (ICHD-2) criteria. In all patients, vomiting wassevere enough to cause dehydration requiring hospitalization forintravenous rehydration. Sumatriptan was administered bysubcutaneous injection ((age × 4 + 20)/100 × 3 mg) or nasalspray (20 mg). All patients who were admitted to our hospitalwere initially administered sumatriptan subcutaneous injectionsand were carefully observed for responses and adverse effects.Some patients were individually instructed on how to use thenasal spray. Their responses were classified as: (1) Complete,no vomiting after treatment with sumatriptan; (2) Effective, lessthan half the frequency (compared with the last attack withoutsumatriptan) of vomiting after treatment with sumatriptan; and(3) Non-effective. The Kruskal–Wallis rank sum test was usedto compare family history of migraine among the 3 responsegroups. The use of sumatriptan for CVS attacks in children andadults was approved by the Ethics Committee of the TeikyoUniversity School of Medicine (No. 07078).MAIN RESULTS: Sumatriptan was administered for 42 CVSattacks suffered by the 12 patients in the trial. Eleven patients,suffering 31 attacks, were treated by subcutaneous injection ofsumatriptan. Of these 11 patients, 4 patients showed completeresolution (7 complete and 1 non-effective response) in 8 attacksand 5 patients showed an effective response (12 effective and 10non-effective responses) in 22 attacks. Five patients weretreated for 6 attacks with sumatriptan nasal spray. Of these 5patients, 1 patient showed complete resolution (1 completeresponse), 1 patient showed effective resolution (1 effectiveresponse), and 3 patients showed non-effective resolution (4non-effective responses) in 6 attacks. We observed no adverseeffects associated with sumatriptan administration. A familyhistory of migraine in a first-degree relative was found in 33% (4of 12) of the patients. There is no statistical relationshipbetween the effectiveness of sumatriptan and family history ofmigraine.CONCLUSION: In at least 9 patients (75%), vomiting wasreduced after administration of sumatriptan. We conclude thatsumatriptan will be an effective agent for the treatment ofpatients with CVS.OBJECTIVE: In Taiwan, the guideline for determination of braindeath in children was established in 2004 which only approved forabove 3 years of age. Facing the fact that there has been increasingdemand for the establishment of criteria for diagnosis of braindeath in young children, we conducted a study of literature reviewof the guideline of brain death determination in majorrepresentative countries from different areas in the world.METHODS: During a period of 6 months, a project of literaturereview of the guideline of brain death determination of 16countries from the world, including USA, UK, France, Germany,Italy, Spain, Finland, Sweden, China, Japan, South Korea, Israel,Saudi Arabia, Australia, South Africa and Taiwan. The contents oftheir guidelines were analyzed and compared.MAIN RESULTS: Most countries established their laws andguidelines. Only USA has its special guideline for the children.Other than Taiwan (> 3 years old) and Finland (> 1 year old), theguideline can be applied to infant ages. Most countries agree toadopt 6 reflexes for the evaluation of brainstem functions: Doll’seye test, light reflex, corneal reflex, Caroli test, deep pain and gagreflex. Most countries adopt apnea test for the evaluation ofrespiratory potential. Most countries request 2 specialists for thedetermination of brain death, except only 1 needed in Sweden and3 needed in Italy. The observation period is 6 to 12 hours inmajority, but 4 hours in Australia and 24 hours in Saudi Arabia.Some countries request longer period for younger children. Theinterval between testing varies a lot. It is 2 hours in Sweden &Australia, 4 hours in Taiwan, the others range from 6 to 12 hours.Finland and Italy only request for one testing. Confirmatory testsare not necessary in majority. But they are required in France,Italy, Spain and Japan, irrespective of age. They are alsomandatory in different younger ages in USA, Germany, SouthKorea and Saudi Arabia. EEG is the common tool forconfirmation, but isotope cerebral flow and Doppler ultrasonictesting, and evokes potential are also optional.CONCLUSION: The guidelines for determination of brain deathin children in the world seem reach a general concept, but vary inthe procedures. A longer observation period for younger childrenmay become mandatory. Furthermore, confirmatory tests for thediagnosis of brain death in children younger than one year old maybe needed.[Keywords]brain death determination, guideline, children[Keywords]International Headache Classification; cyclic vomitingsyndrome (CVS); migraine; sumatriptan124

FP17-01REFERRAL NETWORK IN ASIA: DATABASEREVIEW 2001 – 2009Pamela P.W. Lee, Koon-Wing Chan, Wilfred H.S.Wong,Marco H.K. Ho, Tsz-Leung Lee, Yu-Lung LauDepartment of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine,The University of Hong Kong (HKU), Hong KongOBJECTIVES: Primary immunodeficiency disorders (PIDs) areinborn errors of the immune system. Because of their rarity,multi-center collaboration for pooled data analysis and molecularstudies is important to gain meaningful insights about the phenotypicand genetic diversities of PIDs. Since 2001, our unit establishedcollaboration with more than 20 pediatric centers in China andSoutheast Asia. It is imperative to organize the data systematically toyield information on epidemiology of PIDs in this region.METHODS: In 2009, a web-based PID patient database wasestablished by HKU, and a full database review was performed. Thepassword-protected database contains clinical and mutation data ofpatients referred to our unit for genetic diagnosis. All referringdoctors have access to information of patients under their care. Aweb-based referral system was incorporated, where referring doctorscan make requests for genetic tests and provide clinical data in astandardized format. Appropriate genetic tests will be performedafter detailed discussion, based on patient’s clinical andimmunological phenotype.MAIN RESULTS: 619 entries were recorded, including 344 genetictests performed on 289 patients and 275 carrier screening.Eighty-nine patients (30.8%) were from Hong Kong, 150 (51.9%)were from mainland China while the rest were from Taiwan,Singapore, Malaysia, Thailand, the Philipines and Australia.Mutations in PID genes were confirmed in 176 patients, and 157carriers were identified. X-linked agammaglobulinemia (n=69),Wiskott-Aldrich syndrome (n=36), X-linked chronic granulomatousdisease (CGD, n=22), X-linked hyperIgM (n=15) and X-linkedsevere combined immunodeficiency (SCID, n=13) constitutedmajority of cases. We also identified mutations of rare PIDs, such asautosomal-recessive SCID (IL7R, JAK3, RAG2 and DCLRE1C),autosomal-recessive CGD (NCF1, CYBA), defects ofIL12/IFN-gamma axis in patients susceptible to mycobacterialinfections, FOXP3 mutation inimmunodysregulation-polyendocrinopathy-X-linked (IPEX)syndrome, SH2D1A mutations in X-linked lymphoproliferativesyndrome, and ITGB2 mutations in leucocyte adhesion deficiency.However, mutations could not be identified in 40% of patientsdespite distinct clinical and immunological phenotypes. Overall,children with PIDs were diagnosed at a much earlier age in the recentyears, but in China many patients with life-threatening PIDs diedvery young because of limited access to transplant service.CONCLUSION: Establishment of PID database and referralnetwork is an initial step to multi-center collaboration. Thisconstitutes the foundation for PID research and documentation ofprevalence, disease burden and outcome of patients with PIDs.Currently we offer genetic tests on 50 PID genes, and more are underdevelopment. New genetic technology, such as microarray andexome sequencing will enable efficient ways of molecular diagnosis.FP17-02CLINICAL FEATURES AND GENETIC ANALYSISOF 110 CASES WITH PRIMARYIMMUNODEFICIENCY IN CHILDRENHua-Song ZENG , Xiang-Yuan CHEN, Ru WEI, PingZENG, Feng LIDepartment of Allergy,Immunology and Rheumatology,Guangzhou Children'sHospital,Guangzhou Medical College, Guangzhou Women and Children’sMedical Center,Guangzhou,, China,510120OBJECTIVE: To analyze the clinical features and geneticdiagnosis of 110 cases with primary immunodeficiency.METHODS: Retrospective reviewed analysis was performedto the PID cases according to the inpatient records of allpatients hospitalized between 1999 to 2009.RESULTS: Among 2004-2009 ,there were 85.5% (94/110)cases of PID were diagnosed and only 14.5%(16/110) caseswere diagnosed before 2004,only 15.5%(17/110) cases hadgenetic diagnosis.The ratio of male to female is 90:20.Themajor subject of PID is humoral immunodeficiency, including71.43%(30/42) cases with agammaglobulinemia, 14.29%(6/42)cases with Hypogammaglobulinemia,11.90%(5/42) cases withselectivity IgA deficiency,2.38%(1/42) cases with CD 19deficiency. There were 34.55%(38/110) cases with combinedimmunodeficiency, including two cases with Hyper IgMsyndrome,12.73%(14/110) cases with dseases of immunedysregulaton, 0.91%(1/110) with WAS,1.82%(2/110) caseswith CGD,3.64%(4/110) cases with Hyper IgE syndrome,Thereare 16.36%(18/110) cases with positive family history,85.45%(94/110) cases with fever, 88.18%(97/110) cases withupper respiratory tract and sinusitis infection, 68.18%(75/110)cases with lower respiratory tract infection,51.82%(57/110)cases with diarrhea,34.55%(38/110) cases withmalnutrition.10.91%(12/110) cases died in hospital,and twopatient died at home.The ratio of PID patients to inhospitalpatients is 110:200000. Genetic diagnosis found CYBBmutation in 2 CGD cases, CD40L mutation in 2 HIGM case,IL2RG mutation in 5 combined immunodeficiency case, BTKmutation in 6 XLA cases. SATA3 mutation in 2 cases withHyper IgE syndrome.Nobody had eradicated treatment such asbone marrow transplantation but symptomatic treatment.CONCLUSION: PID is one group dieases which seriouslythreat life with a high mortality.With the development ofmedical science, the diagnosis and treatment of PID had beenimproved greatly. But the genetic diagnosis and eradicatedtherapy need to be improved in Guangzhou,China[Keywords] children;primary immunodeficiency; gene[Keywords]Primary Immunodeficiency Disorder, Asia, Network, Database125

FP17-03IDENTIFICATION OF NOVEL EPITOPES OF β2GLYCOPROTEIN I (β2GPI) RECOGNIZED BYIGA AUTOANTIBODIES IN CHILDHOODHENOCH-SCHÖNLEIN PURPURAYao-Hsu Yang, MD, PhD 1 , Chun-Jung Chang, PhD 1 ,Ya-Hui Chuang, PhD 2 , Hui-Yao Hsu 1 , Bor-Luen Chiang,MD, PhD 11Department of Pediatrics, National Taiwan University Hospital, College ofMedicine, National Taiwan University, Taipei, Taiwan; 2 Department of ClinicalLaboratory Sciences and Medical Biotechnology, College of Medicine,National Taiwan University, Taipei, TaiwanOBJECTIVES: IgA anticardiolipin (aCL) antibodieshave been found in Henoch-Henoch-Schönlein purpura(HSP). The aim of this study is to test the hypothesisthat β2 glycoprotein I (β2GPI) may be the antigenictarget for IgA (aCL) antibodies in HSP.METHODS: The reactivity of plasma samples andpurified polyclonal IgA with cardiolipin (CL), β2GPI,and β2GPI-derived peptides was analyzed byenzyme-linked immunosorbent assay (ELISA).RESULTS: At the acute stage, HSP patients hadsignificantly higher plasma levels of IgA antibodiesagainst β2GPI. Furthermore, we identified a variety ofβ2GPI-dereived peptides (P3, P5, P7, P11, and P12)that were recognized by IgA anti-β2GPI antibodies.The plasma levels of IgA antibodies against abovepeptides were also higher in HSP patients than incontrols. IgA anti-β2GPI antibodies were associatedwith the presence of joint manifestations (p=0.0341)and heavy proteinuria (p=0.0028), and well correlatedwith IgA aCL antibodies (r=0.48, p= 0.015). Moreover,polyclonal IgA from plasma samples positive for bothIgA aCL and IgA anti-β2GPI antibodies bound well toβ2GPI rather than CL alone.CONCLUSIONS: These findings reveal the presenceof IgA anti-β2GPI antibodies in childhood HSP andsuggest that β2GPI may be an important autoantigenfor HSP. Further studies are necessary to clarify thereal role of these antibodies in HSP.[Keywords]Henoch-Henoch-Schönlein purpura, children, beta2glycoprotein I, peptides, autoantibodiesFP17-04IMMUNE MECHANISM OF CO-INFECTION INNOVEL H1N1 INFLUENZA INFECTION-POORNK CELL CYTOTOXICITY AND SUPPDRESSEDINNATE IMMUNITYLin Wang, Chi-Chen Wei (Co-first author), Chung-ChengLi, Ling-Sai Chang, Kuo-Shu Tang, Chiu-Chiang Wu,Hong-Ren Yu, Kuender D. YangDepartments of Pediatrics, and Medical Research, Chang Gung MemorialHospital-Kaohsiung Medical Center, Kaohsiung, TaiwanOBJECTIVE: Fatality of swine-origin novel H1N1 influenzainfections is known to relate to co-infections. Human hostimmune responses following infection with the novel pandemicinfluenza A virus (H1N1) are poorly understood. In thisinfluenza A/H1N1 09 pandemic, we conducted acomprehensive study to clarify the immunopathogenesis ofinnate and adaptive responses in patients with novel H1N1infection.METHODS: In a cohort of 111 flu-like patients, 65 novelH1N1 infections with RT-PCR-confirmation and 46 othernon-H1N1 febrile illness (OFI) patients were subject toassessment of immunity related to viral and bacterialinfections. Quantitative and qualitative immune mediatorsrelated to viral and bacterial defenses were studied. Differencesin viral defense functions and bacterial defense mediatorsbetween novel H1N1 and non-H1N1 controls were assessed.RESULTS: Results demonstrated that H1N1-infected patientshad significant lymphopenia along with decreases of bothCD4 + and CD8 + T cells, but not NK cells. However, immunefunctions for virus defense in perforin-expression of NK cellswere significantly decreased (116.8 ± 11.4 / L vs. 203.1 ±38.2 / L, P= 0.038), and the cell cytolytic activity of NK cellswere also significantly impaired (23.1 ± 9.8 % vs. 68.9 ± 4.9 %at 40:1 effector vs. target cells ratio; P= 0.001) in H1N1patients on comparison to those in OFI patients. Th1 cytokines,IFN- , but not interleukin-12 (IL-12) was significantdecreased (34.8 ± 3.5 pg/mL vs. 82.1 ± 17.8 pg/mL, P= 0.012).Neither Th2 cytokines (IL-4, IL-10, and IL-13) nor Th17cytokine (IL-17) were different between H1N1 and OFIpatients. Immune functions for bacterial defenses in C-reactiveprotein (CRP) and IL-6 were significantly depressed in novelH1N1 patients. IFN- production that is important forintracellular bacterial killing was also significantly depressedin H1N1 patients (P= 0.012).CONCLUSION: In novel H1N1 influenza infections, viraldefense functions such as perforin expression and NK cellcytotoxicity were depressed; bacterial defense functionsincluding CRP production, IL-6 levels and IFN- productionwere also depressed. This may in part explain why novel H1N1patients frequently died of co-infections. Further investigationto correct the immune functions of viral defenses on NK cellactivity and mediators for bacterial defenses may decreasefatality due to co-infections in novel H1N1 infections.126

FP17-05CLINICAL AND HOST GENETICCHARACTERISTICS OF MENDELIANSUSCEPTIBILITY TO MYCOBACTERIALDISEASE IN JAPANTakada Hidetoshi 1 , Takayuki Hoshina 2 , MasatakaIshimura 3 , Takehiko Doi 4 , Toshiro Hara 5Department of Pediatrics, Graduate School of Medical Sciences, KyushuUniversity 1 , Pediatrics, Graduate School of Medical Sciences, KyushuUniversity 2 , Department of pediatrics, Graduate school of medical sciences,Kyushu University 3 , Pediatrics, Kyushu University 4 , Department of Pediatrics,Graduate School of Medical Sciences, Kyushu University 5 (Japan)Mutations of IFNGR1, IFNGR2, IL12B, IL12RB1,STAT1, and NEMO have been found to be responsiblefor a part of Mendelian susceptibility to mycobacterialdiseases (MSMD) which are characterized by recurrentand severe intracellular bacterial infections. However,there are no data on the clinical and host geneticcharacteristics of MSMD in Japan. In this study, weanalyzed fifty patients who had severe and recurrentintracellular infections from 1999 to 2009. The clinicalmanifestation and genetic background wereinvestigated. Furthermore, IFN-γR1 expression levelson monocytes, and intracellular TNF-α productionwere analyzed. Among MSMD patients, BCGinfection, especially BCG osteomyelitis was the mostcommon manifestation. There were no Salmonella orListeria monocytogenes infections. The median intervalbetween BCG vaccination and BCG infection was 11months (5-46 months). Six patients were found to havedominant partial IFN-γR1 deficiency, and 1 patient hadNEMO mutation. IFN-γR1 expression on monocyteswas increased in all IFN-γR1 deficiency patients. In apatient with NEMO mutation, monocytic intracellularTNF-α production was defective. MSMD patients inJapan seem to have a different clinical and geneticfeature compared with those in Western countries. Asignificant number of patients with recurrent ordisseminated mycobacterial infections withoutmutations in known 6 genes suggest other unknowngenetic factors in this disease. Analysis of IFN-γR1expression on monocytes and monocytic intracellularTNF-α production are useful for the screening ofMSMD.COLLABORATORS: Koichi Oshima, Osamu Ohara(RIKEN), Takashi Kanazawa, Kohichi Arakawa,(Gunma University), Tomoki Kawai, RyutaNishikomori, Tatsutoshi Nakahata (Kyoto University),Satoshi Okada, and Masao Kbayashi (HiroshimaUniversity.FP17-06MICRORNA-125B MEDIATES AUGMENTATIONOF TNF-α PRODUCTION BY NEONATAL CD14MONOCYTES VIA POST-TRANSCRIPTIONALREGULATIONHsin-Chun Huang, Hong-Ren Yu, Hui-Chen Huang,Chieh-An Liu, Te-Yao Hsu*, Chia-Yo Ou*, Kuender D.Yang †Departments of Pediatrics and Obstetrics*, Chang Gung MemorialHospital-Kaohsiung Medical Center, Graduate Insititute of Clinical MedicalScience, Chang Gung University College of Medicine, TaiwanOBJECTIVE: Neonates although immunodeficient but frequentlyreveal augmented proinflammatory reactions in sepsis or chronic lungdisease. Our previous study revealed neonatal leukocytes producedmore interleukin-8 (IL-8) in blood. Since CD14 monocytes are keyleukocytes for the bridge between innate and adaptive immunity.Investigated different proinflammatory response of CD14 monocytesbetween newborns and adults and studied what mechanism causedaugmented TNF-α production by neonatal monocytes.METHODS: Blood leukocytes were separated intopolymorphonuclear (PMN) and mononuclear cells (MNCs), andCD14 + monocytes were enriched from MNCs for studies. Leukocyteswere cultured in RPMI with 10%FBS in the presence or absence oflipopolysaccharide (LPS), RNA samples were subjected tomeasurement of IL-8 and TNF-α mRNA, and screening of 470microRNAs (miRNAs) by Illumina microarray followed by real-timePCR validation of miRNA that had more than 2-fold increase ordecrease of expression. Electrophoretic mobility shift assay (EMSA)was used to measure NF-κB transcription factor activation betweenneonatal and adult MNCs. MiR-125b precursors was used to transfectinto the CD14 monocytes for functional validation. Mann-Whitney Utest were used for group comparisons, a p value < 0.05 was consideredstatistically significant.MAIN RESULTS: Neonatal PMNs produced higher IL-8 than adultPMNs. Neonatal monocytes released significantly higher TNF-α butnot IL-8 levels than adult monocytes. Assessment of the transcriptionfactor NF-κB for IL-8 and TNF-α induction found a lower NF-κBactivation in neonatal MNCs suggesting a posttranscriptionalmechanism for augmented TNF-α production in newborns. A screeningof 470 microRNAs was performed to explore whether miRNAs wereinvolved in the augmentation of TNF-α production. Twenty-sixmicroRNAs related to regulation of TNF-α induction were searchedfrom the Sanger website. Of these 26 microRNAs, four microRNAs(miR-125b, miR-103, miR-130A, miR-542-3P) were found more than2- fold decrease or increase between neonatal and adult monocytesafter LPS stimulation. Functional validation by real-time PCR analysisidentified miR-125b significantly decreased and correlated to themRNA and protein levels of TNF-α in neonatal monocytes after LPSstimulation. Transfection of miR-125b precursor into monocytessignificantly repressed the TNF-α mRNA and protein expression.CONCLUSION: Neonatal leukocytes have altered proinflammatoryreaction in response to LPS that is not mediated by transcriptionalcontrol but post-transcriptional regulation by miRNAs. Lower level ofmiR-125b negatively regulated TNF-α expression in neonatal CD14monocytes. Modulation of miRNA expression may be used to regulateabnormal inflammatory reaction in newborns.[Keywords]CD14, TNF-α, microRNA, neonate, post-transcription[Keywords] Primary immunodeficiency, Mendelian susceptibility tomycobacterial disease127

FP18-01LIVING DONOR LIVER TRANSPLANTATIONFOR TWO SISTERS OF PROGRESSIVEFAMILIAL INTRAHEPATIC CHOLESTASISTYPE 2: NOVEL GENETIC FINDING ANDIMPACT ON GROWTHHirotaka Shimizu 1 , Katsuhiro Arai 1 , Mureo Kasahara 2National Center for Child Health and Development Department ofGastroenterology, Japan 1 ; National Center for Child Health and DevelopmentDepartment of Transplantation, Japan 2OBJECTIVES: Progressive familial intrahepatic cholestasistype2 (PFIC-2) is a syndrome in which children develop severecholestasis progressing to biliary cirrhosis and chronic liverfailure. Synthesized bile acids are transported across thecanalicular membranes by ATP-dependent pump. This pump isknown as the bile salt export pump (BSEP) and defect in thispump due to a mutation in the ABCB11 gene causes PFIC-2.We experienced two siblings of PFIC-2 who underwent livingdonor liver transplantation (LDLT).CASE REPORT: The elder sister developed jaundice andacholic stool at 4 months old. Hyperbilirubinemia and elevatedAST, ALT, and serum total bile acid (TBA) persisted, but serumGGT remained within normal range. At 7 month old, pruritusworsened and caused significant sleep disturbance. Failure tothrive and ascites appeared without diarrhea. LDLT from herfather was performed at the age of 1 year-2 month old. After thetransplantation, clinical symptom and laboratory findingssignificantly improved. She had significant growth failure withheight of -5.6SD and weight of -2.8SD at the age of1year-6month. However, her growth had improved dramaticallyto height of -0.6SD and weight of 0.7SD by 1.5 years after thetransplantation. The younger sister developed jaundice at 1month old, and pruritus became significant by 3 months old. Herclinical presentation was similar to her elder sister.Hyperbilirubinemia, elevated AST, ALT and serum TBA, normalGGT, and severe pruritus were confirmed. At 9 months old,LDLT from her mother was performed. Electron microscopy ofexplanted liver revealed dense and amorphous bile and it wasconsistent with PFIC-2. After the transplantation, pruritusdisappeared and quality of life improved dramatically. A largenumber of genetic mutations of ABCB11 gene have beendescribed. Genetic testing revealed two sisters have exactly thesame two mutations (S901R, C1083Y), and father and mother isheterozygote for S901R and C1083Y mutation, respectively. Thepredictive models using Grantham, SIFT and Polyphen suggestthis compound heterozygous state are “damaging” to the BSEPfunction. With further analysis, we concluded that thesemutations are the novel one for PFIC-2.CONCLUSION: Considering the progressive nature of thisdisease and the risk for the hepatocellular carcinoma, whendiagnosis of PFIC-2 is definite and patient suffers from severepruritus with impaired QOL or growth retardation withprogresses to cirrhosis and liver dysfunction, early livertransplantation should be considered as an ultimate therapy.[Keywords]Progressive familial intrahepatic cholestasis type 2,Pediatric liver transplantation,Mutation analysisFP18-02RBMY GENE EXPRESSION ASSOCIATED WITHPOOR SURVIVAL IN HEPATITIS B VIRUSRELATED MALE HEPATOCELLULARCARCINOMA PATIENTYu-Wun Liao 1 , Jia-Feng Wu 1 , Yen-Hsuan Ni 1 , Huey-LingChen 1 , Hong-Yuan Hsu 1 , Mei-Hwei Chang 1Department of Pediatrics, National Taiwan University Children HospitalNational Taiwan University College of Medicine, Taipei, Taiwan 1OBJECTIVES: The RNA-binding motif gene on Ychromosome (RBMY gene), encoding a male germcell-specific RNA binding protein associated withspermatogenesis, was found integrated by hepatitis B virus(HBV) DNA in a childhood hepatocellular carcinoma(HCC) tissue. The RBMY transcripts, expressed exclusivelyin the testis of normal people, were detected by reversetranscription – polymerase chain reaction in 36% of HCCsfrom 90 males and in 67% of hepatoblastoma from six boysin previous study. This study is aimed to evaluate theclinical correlation between RBMY expression and survivaland tumor staging, among HBV related HCC patients.METHODS: The paired tumor and nontumor tissues werefrom 76 male cases of primary HCC, and analysed byRT–PCR using primer pairs specific to the exons 2 and 5 ofRBMY gene. The human porphobilinogen deaminase(PBGD) transcripts were also amplified as an internalcontrol. A 473-bp cDNA fragment could be amplified onlyfrom RBMY-expressing tissues, while a 273-bp PBGDcontrol band was amplified from all tissues. We hadreviewed the medical records of these patients to determinethe tumor staging according to American Joint Committeeon cancer (AJCC) and Barcelona clinic liver cancer(BCLC) staging system. We also study the survival time,HBV status for these patients, retrospectively.Kaplan-Meier method and Cox proportional hazards modelwere used for survival analysis.MAIN RESULTS: Among total 76 male HCC cases, 56subjects had HBV infection. RBMY were positive in 23subjects (41%), and negative in 33 subjects (59%),respectively in HBV related HCC (n=56). The survivalanalysis was carried out in these 56 subjects with HBVassociated HCC diagnosed between 7.5 to 72.7 years ofage. Cox proportional hazards model showed significantstatistic difference between the two group with or withoutRBMY expression (P=0.01).CONCLUSION: RBMY gene expression is associatedwith poor survival in Hepatitis B virus related malehepatocellular carcinoma patients.[Keywords] RBMY gene, HBV, HCC128

FP18-03MONITORING 6-THIOGUANINE NUCLEOTIDECONCENTRATIONS IN JAPANESE CHILDRENAND ADOLESCENTS WITH INFLAMMATORYBOWEL DISEASEYo Aoyagi 1 , Yoshikazu Ohtsuka, 1 Katsuhiro Arai, 2 TohruFujii, 1 Takahiro Kudo, 1 Satoru Nagata, 3 ToshiakiShimizu 11 Department of Pediatrics and Adolescent Medicine and 3 Division ofProbiotics Research, Juntendo University School of Medicine, Tokyo, Japan; 2Division of Gastroenterology, Department of Medical Specialties, NationalCenter for Child Health and Development, Tokyo, JapanBACKGROUND: 6-mercaptopurine (6-MP) andazathioprine (AZA) are widely used as maintenancetherapy in children with inflammatory bowel disease(IBD). However, proper 6-thioguanine nucleotide(6-TGN) concentrations in Japanese IBD children havenot been reported.METHODS: This is the retrospective review of 34ulcerative colitis (UC) patients and 21Crohn’s disease(CD) patients (13.57±4.76 years old) required 6-MP orAZA to maintain their disease remission. All of them weretreated with AZA or 6-MP at least for 3 weeks prior to thisstudy in addition to previous treatment with mesalazine,corticosteroids, or nutritional management. 6-TGN levels,assayed by high-performance liquid chromatography, andlaboratory data were monitored throughout the study.6-MP was initially started at approximately 0.5 mg/kg/dayand the dose was titrated as needed.RESULTS: Thirty-six children were successfully kept inremission after weaning off corticosteroids with 6-MP andAZA therapy. Among all, 128 measurements (62 fromactive disease, 66 from in remission) were analyzed. Themean 6-MP dose with active disease (0.904 ±0.331mg/kg/day) was significantly higher than that in remission(0.743 ± 0.225) (p=0.049). The mean 6-TGNconcentrations with active disease (458.1 ± 279.09pmol/8×108RBC) was significantly lower than that inremission (531.17 ± 217.38) (p=0.028). A significantinverse correlation was found between the WBC countsand 6-TGN concentrations (r= 0.287, p

FP18-05PROBIOTICS CAN RETARD COLONCARCINOGENESIS BOTH IN SEGMENTALORTHOTOPIC COLON CANCER ANDEXTRAINTESTINAL TISSUEChien-Chang Chen 1 , Wei-Chuan Lin 2 , Ming-Wei Lai 3 ,Man-Shan Kong 4 , Hsun-Chin Chao 5 , Shih-Yen Chen 6 ,Tzou-Yien Lin 7Pediatric GI, Chang Gung Children's Hospital,Taiwan 1 , Pediatrics, ChangGung Children’s Hospital 2 , Division of Pediatric Gastroenterology, ChangGung Children's Hospital 3,4,5,6 , Pediatric Infectious Diseases, Chang GungChildren's Hospital, Taiwan 7OBJECTIVE: Usage of probiotics is associated with reducedrisk of carcinogenesis in colon cancer, a major cause of cancerdeaths worldwide. The detail mechanism of probiotics on coloncancer is not fully understood. Chemokine receptor CXCR4 andmajor histocompatibility complex (MHC) class I molecules areover-expressed in human colon cancer tissue and murine cancercells (such as CT26), compared to normal mucosa and benignlesions. Modulation of the intestinal immune response byadministration of probiotics may be an effective strategy forinhibiting tumor growth, or inducing cancer cells apoptosis.METHODS: We pre-inoculated the mice daily with theprobiotics L. acidophilus NCFM (La) at least 2 weeks beforecancer cells implantation. CT26 is anN-nitroso-N-methylurethane-induced murine colonadenocarcinoma cells derived from BALB/c mice. Subcutaneousdorsal-flank tumor and segmental orthotopic colon cancer wereimplanted with CT26 murine colon cancer cells. At necropsy,colon tissues were removed and stained with hematoxylin &eosin, as well as Terminal deoxynucleotide transferase dUTPNick End Labeling assay for labeling DNA breaks to detectapoptotic cells by immunohistochemistry. Lamina propria ofcolon, mesenteric lymph nodes (MLN), and spleen werecollected and purified for flow cytometry and mRNA analysis.MAIN RESULTS: 1) Probiotics La pre-inoculation reducedtumor volume growth 50.3%, compared with untreated mice at28 days after tumor implants (2465.5±937.6 versus4950.0±1137.2mm 3 ,p

FP19-01APPEARANCE OF ACANTHOSIS NIGRICANSMAY PRECEDE OBESITY: EVIDENCE FORTHE INVOLVEMENT OF INSULIN/IGFRECEPTOR SIGNALING PATHWAYChung-Hsing Wang 1,3 , I-Ching Chou 1 , Chang-Hai TsaiTsai 1 , Da-Tian Bau 3,# , Wei-De Lin 2,# , Fuu-Jen Tsai 1,2,4,#1Departments of Pediatrics, 2 Medical Research, and 3 Terry Fox CancerResearch Laboratory, China Medical University Hospital, Taichung, Taiwan; 4College of Health Science, Asia University, Taichung, TaiwanObesity is one of the leading causes of preventabledeath. Complication of child obesity includecardiovascular risks, type 2 diabetes mellitus, impairedglucose tolerance, and acanthosis nigricans (AN). ANis associated with obesity as a manifestation ofcutaneous insulin resistance, while the interactionbetween AN and obesity and detail mechanism for thepre- and co-obese appearance of AN (PCOAN) inchildren are still unrevealed. In this pioneer study, theinvolvement of insulin/IGF receptor pathway inchildren PCOAN was investigated via studying theassociation of polymorphisms of INSR, IRS1, IGF1Rgenes with pre- and co-obese AN. In total, 99 childrenPCOAN patients and 100 healthy controls recruitedwere genotyped and analyzed by PCR-RFLP method.Significantly different distributions were found in thefrequency of the INSR His1085His and IGF1RIVS7-20 genotypes, but not in IRS1 Ala804Ala orIGF1R Thr766Thr genotypes, between the AN andcontrol groups. The T allele of INSR His1085His andthe C allele of IGF1R IVS7-20 both conferred asignificant (p=0.04 and 2.84E-6, respectively)increased risk of PCOAN in children. Our resultsprovide not only the evidence of the T allele of INSRHis1085His and the C allele of IGF1R IVS7-20 arecorrelated with the appearance of AN precede orconcurrence with obesity but revealed that insulin/IGFreceptor pathway may play an important role in thispre- and co-obese AN.[Keywords]Acanthosis nigricans, obesity, insulin, single nucleotidepolymorphismFP19-02STAT5B GENE POLYMORPHISMSCONTRIBUTE TO SERUM TOTALCHOLESTEROL LEVELS IN JAPANESECHILDREN WITH GROWTH HORMONEDEFICIENCY1 Mika Makimura, 1 Kenji Ihara, 1 Kanako Kojima-Ishii,1 Takafumi Nozaki, 2 Hitoshi Kohno, 1 Toshiro Hara1 Department of Pediatrics, Graduate School of Medical Sciences, KyushuUniversity, Fukuoka, Japan; 2 Department of Endocrinology and Metabolism,Fukuoka Children’s Hospital and Madical Center for Infectious Diseases,Fukuoka, JapanBACKGROUND & AIMS: Growth hormone (GH) plays significantroles in lipid metabolism since the patients with GH deficiency sufferfrom obesity or hyperlipidemia, and GH treatment greatly improves thelipid metabolism. We previously reported that GH treatmentprofoundly affected body composition and cholesterol metabolism inchildren with GH deficiency, and GH receptor (GHR) gene Leu544Ilepolymorphism was a genetic factor that affected serum cholesterollevel. In this study, we focused on the JAK2-STAT5 pathway which isthe signal transduction pathway downstream of the GHR, and selectedthe STAT5A/5B genes as candidates which regulate serum cholesterollevel.METHODS: The study population comprised 83 children (61 boysand 22 girls) with idiopathic GH deficiency. The diagnosis of GHdeficiency was made according to the diagnostic criteria proposed bythe Growth Hormone and Its Related Factors Study Committee of theFoundation for Growth Science, Japan. The patients were givenrecombinant human GH in a weekly dose of 0.5 IU/kg (approximately0.19 mg/kg) by daily subcutaneous injection. The serum total and HDLcholesterol levels were monitored before, 3mon, 6mon and 12monafter starting GH treatment. The height, weight, body mass index, andserum IGF-1 were also measured before and 12 months after startingthe GH treatment. For the genetic study, 6 SNPs in the STAT5A/Bgenes were selected by tagSNP picker program on the homepage of theHapMap project, and genotyping was carried out by the TaqMan SNPGenotyping Assay. The subsequent functional study was performed asfollows: the promoter region about 2 kb upstream of the transcriptionstart site of the STAT5B gene was amplified by PCR method withgenomic DNA from a individual with heterozygous carrier of-44816A/G, and two types of vectors with -44816A and -44816G in thepromoter region of the STAT5B gene was constructed. Each vector wastransfected to HeLa cells, HEK293 cells and U937 cells and luciferaseactivity was measured by using Dual-Glo Luciferase Assay System.RESULTS: The genetic study demonstrated that the SNPs in theSTAT5B gene were significantly associated with serum total cholesterollevels both before and after GH treatment in children with GHdeficiency. The luciferase assay showed that the -44816A>G SNP inthe STAT5B gene functionally affected expression levels in vitro.CONCLUSIONS: STAT5B gene was one of the key genes that affectserum total cholesterol level in children with GH deficiency.[Keywords]STAT5; cholesterol; Growth hormone; GH deficiency;JAK2-STAT5 pathway131

FP19-03EXPRESSION PATTERN OF KIR6.2 INSKELETAL MUSCLE CELLS OF PATIENTSWITH FAMILIAL HYPOKALEMIC PERIODICPARALYSISYang-Hee Park, June-Bum KimDepartment of Pediatrics, Konyang University College of Medicine, KoreaFP19-04THERAPEUTIC STRATEGY WITH AXONALTRANSPORTATION PROVIDES THE BASIS FORTREATING CNS DEFICITS ASSOCIATED WITHLYSOSOMAL STORAGE DISEASEDar-Shong Lin 1,2 , Shuan-Pei Lin 1 , Chih-Kuang Chuang 2 ,Tuen-Jen Wang 3Departments of Pediatrics 1 ; Department of Medical Research 2 ; Department ofLaboratory Medicine 3 ; Mackay memorial Hospital, TaiwanOBJECTIVES: Familial hypokalemic periodicparalysis (HOKPP) is an autosomal dominant disordercharacterized by reversible flaccid paralysis andintermittent hypokalemia. Although it has beenreported that decreased activity in the K ATP channels ofthe skeletal muscle cell membrane plays a role in thepathogenesis of HOKPP, a clear mechanism has not yetbeen established. This study aimed to investigate themolecular biological mechanism underlying thedecreased activity of K ATP channels in the skeletalmuscles of familial HOKPP patients by studying thelevels of the K ATP channel subunit Kir6.2.METHODS: We obtained skeletal muscle cells frompatients with familial HOKPP and healthy volunteersand investigated the mRNA level of KCNJ11 and theprotein level of Kir6.2 therein at normal (4 mM) andlow (1 mM, for depolarization) potassiumconcentrations.MAIN RESULTS: When cells obtained from healthyindividuals and HOKPP patients were treated with 4mM potassium buffer, there was no quantitative changein the KCNJ11 mRNA levels and no difference in theKir6.2 protein expression in the cytosol and cellmembrane. On the other hand, when 1 mM potassiumbuffer was used, normal cells showed decreasedexpression of KCNJ11 mRNA and also decreasedexpression of Kir6.2 protein in the cell membrane.However, patient cells treated with the same buffershowed no quantitative change in the levels of KCNJ11mRNA as well as Kir6.2 protein in the cytosol and cellmembrane.CONCLUSION: Our results suggest that, in HOKPPpatients, the Kir6.2 protein may not be transportedfrom the cell membrane to the cytosol, leading toclosure of the K ATP channels, induction ofdepolarization, and subsequently, to the paralyticsymptoms observed in the patient. These findings thusprovide new insights into the pathogenesis of HOKPP.OBJECTIVES: The majority of lysosomal storage diseases(LSDs) contain both CNS and visceral pathology. Currentexperimental designs in animal models use viralvector-mediated gene therapy and/or cell therapy to treat thecentral nervous system (CNS) deficits associated with LSDs.The obstacles in achieving widespread gene expressionthroughout the CNS have hampered the development ofpotential treatments. Designing an experimental paradigmincorporating efficient delivery strategies may increasetherapeutic efficacy for disease indications with global CNSpathology. Previous studies have shown that both vectors andenzymes can be transported axonally to distal regions in CNS.Here we hypothesize that axonal connection network can beharnessed to transfer therapeutics to diseased CNS globally.METHODS: As a model system, we used mice with centralnervous system deficits due to lysosomal storage disease.Tiwtcher mice, an authentic murine model of globoid cellleukodystrophy in humans, were inoculated AAV vectordirectly into brain structures with defined axonal connectionswith other structures. Transgenic enzymatic activity, toxicsubstrate accumulation, neuropathology and clinical phenotypewere evaluated for determination of therapeutic efficacy.MAIN RESULTS: The transgene was delivered to the entirebrain, cerebellum, and spinal cord. The successful transductionof neurons in the CNS resulted in restoration of functionalenzyme activity throughout the entire brain and spinal cord.Neuroanatomical mapping findings of histochemical enzymaticstaining are consistent with the pattern of major axonal circuitin CNS. The toxic substrate accumulation in the CNS wassignificantly reduced associated with reversal of inflammation,axonal damage, and demyelination, and amelioration ofdevastating phenotype.CONCLUSION: Our findings are a breakthrough in terms ofgene therapy to the entire CNS. Targeting the brain structureswith divergent axonal connection is an effective approach forachieving widespread therapeutics distribution throughout theCNS. This therapeutic strategy with axonal transportationmight be promising as gene therapy for CNS deficits associatedwith LSD, but also disorders indications with globalneurodegeneration in future clinical trials.[Keywords]axonal transportation, lysosomal storage disease,neurodegeneration, gene therapy, CNS, viral vector[Keywords]hypokalemic periodic paralysis, potassium channel,depolarization132

FP19-05SCN1A ANALYSIS IN GENERALIZEDEPILEPSY WITH FEBRILE SEIZURES PLUSAND SEVERE MYOCLONIC EPILEPSY ININFANCYZheng-Nan Chin 1 , I-Ching Chou 1,2 *; Wei-De Lin 3 ,Haung-Tsung Kuo 4 , Chung-Hsing Wang 1 , Yu-TzuChang 1 , Chang-Hai Tsai 1,5 , Fuu-Jen Tsai 1,3,61 Department of Pediatric Neurology, Children’s Medical Center, ChinaMedical University Hospital, Taichung, Taiwan, 2 Graduate Institute ofIntegrated Medicine, College of Chinese Medicine, China Medical University,Taichung, Taiwan, 3 Departments of Medical Genetics, China MedicalUniversity Hospital, Taichung, Taiwan, 4 Department of Development andBehavior Pediatrics, China Medical University Hospital, Taichung, Taiwan,5 Department of Healthcare Administration, Asia University, Taichung, Taiwan,6 College of Chinese Medicine, China Medical University, Taichung, TaiwanOBJECTIVES: Febrile seizures are a benign disease, but maybe associated with generalized epilepsy and other nonfebrileseizures, including generalized epilepsy with febrile seizures plus(GEFS plus) and the most severe type, severe myoclonicepilepsy of infancy (SMEI). SCN1A and SCN1B have beenidentified in some families of GEFS plus and in sporadic cases ofSMEI. Mutations in the genes coding for the α1 and β1 subunitof the neuronal sodium channel have been associated withvarious types of epilepsy. In this study, we performed a clinicaland genetic study focusing on SCN1A and SCN1B, using genesequencing to detect genomic deletions/duplications on GEFSplus/SMEI patients.METHODS: From 2003 to 2009, 268 patients with febrileseizures visited the pediatric neurologic out-patient clinic atChina Medical University Hospital. A total of 18 patientsdeveloped GEFS plus and SMEI (12 GEFS plus and 6 SMEI)during these period. These patients underwent a detail medicalrecords, metabolic survey, EEG reports, and brain magneticresonance imaging (MRI). Seizure types and epilepsy syndromeswere classified according to the ILAE criteria. The completeSCN1A and SCN1B coding region, including the intron/exonboundaries, were sequenced on GEFS plus and SMEI patients.MAIN RESULTS: The overall picture of GEFS plus was benignand the EEG was normal or brief generalized discharges of spikeand slow wave. However, the seizure deterioration and metaldecline were noted in SMEI. The EEG of SMEI showed a similarprogression to that of the clinical state, from normal to severelyabnormal. The metabolic survey and brain MRI of all patients,including GEFS plus and SMEI were within normal limits.Sequencing of SCN1B of all patients revealed no mutations.However, SCN1A mutations were found in 66.7% (4/6) in SMEIand none (0/12) in GEFS plus patients. Sequencing of SCN1A inthe patients revealed 4 mutations: 2 missense, 2 frameshift, and15 polymorphisms. There were no mutations detected in thepatients’ parents.CONCLUSION: This study confirms the high sensitivity ofSCN1A for SMEI phenotype. SMEI is a rare progressiveepileptic encephalopathy that is mostly genetically determined.The incidence is approximately 1 per 30,000. Although it is rare,identifying SCN1A mutations may help an early diagnosis, tobenefit counseling, and to avoid use of antiepileptic drugs thatmay have adverse effects. Further studies on the pathogenesis arerequired.FP19-06GHRELIN MRNA AND PROTEIN EXPRESSIONIN FUNDUS OF STOMACH IN POSTNATAL RATSBORN SMALL FOR GESTATIONAL AGEHui-Ming YANG, Meng MAO, Fan YANG, Su-Fei YANG,Ji-Hua CUIPaediatric Department of West China Second University Hospital, ChinaOBJECTIVES: To explore the changes of Ghrelin mRNA andprotein expression in fundus of stomach of rats born small forgestational age (SGA) and to analyze the relationship with thecatch-up growth of postnatal SGA rats.METHODS: The SGA and appropriate for gestational age (AGA)rat models were established by food restriction during the secondand third trimester of pregnancy. The newborn rats were acquiredafter delivery, among which 10 rats were selected randomized fromSGA group and control group at postnatal day 0, day 20 and day40. The fundus of stomach were taken to determine Ghrelin mRNAand protein expression, in which real-time fluorescence quantitivePCR (real-time FQ-PCR) and immunohistochemistry (IHC) wereused respectively.RESULTS: At postnatal day 0, stomach fundus Gherlin mRNAexpression is higher in SGA rats from food restriction groups thanthose in AGA rats from food restriction or control groups(p0.05). At postnatal day 0 , stomach fundus Gherlin IOD inSGA rats from food restriction groups is higher than AGA ratsfrom food restriction and control groups(p

FP19-7GENOME-WIDE SCREEN FOR SUBMICROSCOPICCHROMOSOMAL ABERRATIONS BY HIGHDENSITY OLIGONUCLEOTIDE ARRAY(AFFYMETRIX SNP 6.0) IN CHILDREN WITHUNEXPLAINED MENTAL RETARDATION ANDDYSMORPHIC FEATURESNi-Chung Lee M.D. 1, 2 , Ling-Hui Li PhD. 3 , AnneChung-Hui Tsai M.D. 3,4 , Wuh-Liang Hwu M.D. PhD. 1, 2 ,Yin-Hsiu Chien M.D. 1, 2 , Jer-Yuan Wu PhD 3 , Yuan-TsongChen M.D. PhD. 3Department of Medical Genetics and 2 Pediatrics,National Taiwan UniversityHospital and National Taiwan University College of Medicine, NationalTaiwan University; Taipei, Taiwan; Institute of Biomedical Sciences, AcademiaSinica, Taiwan 3 ; University of Colorado Health Sciences Center 4BACKGROUND: Rare copy number variation is one of themost common etiologies of unexplained mental retardation anddysmorphic features. Genome-wide high density oligonucleotidearray is a powerful technology that allows for the detection ofDNA copy number changes that previously not detectable byconventional cytogenetic techniques. The aim of this study is toevaluate the clinical utilization of high density oligonucleotidearray in the context of Clinical Genetics.MATERIAL AND METHODS: Affymetrix® Genome-WideHuman SNP Array 6.0 was applied to a total of 14 children withunexplained mental retardation and dysmorphic features withnormal karyotype reports. Patient and parents were ascertainedconcurrently with three chips performed and analyzed as a trioset to distinguish de novo from inherited copy number variations.Identified chromosomal abnormalities were confirmed bygenomic qPCR method.RESULT: On array analysis, 3 out of the 14 children (21.4%)have de novo causally related chromosomal aberrations withsizes ranging from 672kb to 11.7 MB. Case 1 has an interstitialdeletion of 3.9MB at 16p13.12-13.13. She presented multiplecongenital anomalies, including bilateral diaphragmaticeventration, dysmorphic features, midgut rotation, congenitalheart disease, hypotonia, and loose joints. Case 2 has a deletionof 11.7 MB at 6q25.3-qter. She presented microcephaly,psychomotor retardation, and dysmorphism. Case 3 has adeletion of 672kb at 16p11.2, which is a rare CNV associatedwith autism, developmental delay, and mental retardation. Hisclinical presentation includes mild dysmorphic features, Chiarimalformation, psychomotor retardation, and inattention andhyperactivity.CONCLUSION: Use of microarray in clinical practice hasgreatly increased the detection sensitivity of genetic diagnosis.Our data demonstrated the diagnostic value of applying thistechnology in patients with mental retardation and dysmorphicfeatures.[Keywords] Oligonucleotide array, mental retardation, dysmorphismFP20-1CAN EPHEDRINE BE USED AS AN EFFECTIVEPRETREATMENT AGENT IN PREVENTINGADVERSE REACTIONS ASSOCIATED WITHANTIVENOM SERUM (AVS) TREATMENT INPAEDIATRIC PATIENTS?(Six paediatric case studies examining the adverse reactions profile)C.Fernando 1 , TADN Ranasinghe 2 , A Wijekoon 3 , PSSeneviratne 4 , A.Senaratne 51 Consultant Anaesthestist 2&3 Consultant Paediatricians 4&5 Senior house officersin paediatrics (Sri Lanka)INTRODUCTION: Polyvalent AVS administration is the onlyeffective treatment available for systemic envenomation due tosnake bites.AVS treatment is commonly associated with severeadverse reactions. There are several pretreatment regimensavailable for the prophylaxis of severe adversereactions.Hydrocortisone, Promethazine, Chlorpheneramine(Piriton) and adrenaline are widely used as pretreatment agentseither alone or in various combinations. Use of ephedrine, asympathomimetic, as a pretreatment agent has not been exploredor reported. We examined the side effect profile of the AVS afteradministering two different pretreatment regimens, one usingHydrocortisone alone and the other using Hydrocortisone plus acombination of Chlorpheneramine, Ranitidine and ephedrine.MATERIALS AND METHODS: From 1 st January 2009 to 31 stOctober 2009 six children needed AVS treatment. Of them firstfour children( Child A,B,C and D) were given Hydrocortisonealone as a bolus 10 minute prior to AVS followed by 1000mg as anIV infusion concurrently with AVS.The last 2 children (Child Eand F) were given age adjusted doses ofChlorpheneramine,Ranitine and Ephedrine in addition toHydrocortisone given as above. Ten (10) vials of polyvalent AVSof equine origin manufactured by VINS Bioproduct Ltd,India wasdissolved in 100ml of saline was administered as an intravenousinfusion over 40-60 minutes. The patients were continuouslymonitored and the adverse reactions were managed accordingly.RESULTS: Children who received Hydrocortisone alone (ChildA, B, C and D) as pretreatment developed severe adverse reactionsand one child (D) died few hours after AVS treatment despitevigorous resuscitation as a result of severe anaphylactic reaction.The two children (E and F) who received Chlorpheneramine,Ranitidine and Ephedrine in addition to Hydrocortisone did notdevelop severe adverse reactions and they received more than onecycle (10 vials) of AVS.CONCLUSION: Polyvalent AVS of equine origin manufacturedby VINS Bioproduct Ltd, India is commonly associated withsevere adverse reactions when used in paediatric patients. Theregimen of Chorpheneramine, Ranitidine and Ephedrinepretreatment successfully prevented development of severeadverse reactions and permitted repeating AVS treatment ifrequied.Therefore we suggest the use of Ephedrine as apretreatment agent, in preventing adverse reactions associated withAVS treatment, should be explored.[Keywords]Polyvalent anti venom serum(AVS),Pretreatmentagents,Ephedrine,Adverse reactions134

FP20-2PATTERN OF CIGARETTE SMOKING AMONGTHAI ADOLESCENTS: A LONGITUDINALSTUDY FROM INTERNATIONAL TOBACCOCONTROL POLICY.Tawima Sirirassamee, MD. 1 , Buppha Sirirassamee,Ph.D. 2 , Ron Borland, Ph.D. 3 and Geoffrey T Fong, Ph.D. 4 .Srinakarinwirot University 1 , Institute for Population and Social Research 2 , TheCancer Council Victoria 3 , University of Waterloo 4 (Thailand)OBJECTIVE: To determine the pattern of cigarette smokingamong Thai adolescents over a period of three years.METHODS: A longitudinal study was conducted amongadolescents between the ages of 13-18 sampled from 5regions of Thailand using stratified multistage sampling.Wave 1 survey involved 1,000 adolescents was conductedduring January to March 2005, wave 2 survey involved 962adolescents was conducted during July to September 2006and wave 3 survey involved 1,096 adolescents was conductedduring January to March 2008. Self administeredquestionnaires were employed for data collection. Data wereanalyzed and compared using descriptive statistics.MAIN RESULTS: Overall, smoking prevalence hasincreased from 11.3% in wave 1 to 13.7% in wave 2 and18.3% in wave 3. Consistent with other Asian countries,smoking prevalence in young males were more than 10 timeshigher than young females. Among youth smokers, more than70% smoked factory-made cigarette. The total amount oftobacco use per day increased from wave 1 to wave 3. Inwave 1, no one reported that they smoked more than 20cigarettes per day but in wave 2 and wave 3 surveys 6.9% ofyouth smokers reported that they smoked more than 20cigarettes per day. In wave 1, approximately half (47.9%) ofyouth smokers reported that they obtained cigarette fromfriends with only 38% reported that they bought cigarette forthemselves. The proportion of young smokers who reportedthat they bought cigarettes for themselves were significantlyincreased in wave 2 (61.3%) and wave 3 (68.2%) as compareto wave 1. More than half of young smokers reported thatthey tried to quit smoking within the past month. Theproportion of youth smokers who reported that they nevertried to quit smoking were slightly decreased from wave 1 ascompare to wave 2 and wave 3 (20.7% in wave 1, 19.7% inwave 2 and 17.4% in wave 3).CONCLUSION: cigarette smoking among Thai youthremains the important problem and needs further tobaccocontrol policies to prevent and control tobacco consumption.[Keywords]Adolescents, Smoking, ThailandFP20-3INVESTIGATION OF FEVER KNOWLEDGEAMONG KINDERGARTEN TEACHERSWarren SuSuperus Children Clinic, TaiwanOBJECTIVE: Preschool age children are the most susceptibleage group to viral infection of which fever is the most commonpresenting symptoms. If knowledge about fever is correctamong kindergarten teacher, they can play a major role torelease the anxiety of parents. The purpose of this study was toevaluate the fever knowledge of teachers in kindergarten.METHODS: A self-constructed questionnaire includedsources of fever knowledge, perception of fever knowledge andmanagement of fever was used. 351 kindergarten teachers inPingtung county were enrolled. All the participants werefemale.MAIN RESULTS: The main source of fever information wasfrom health professions and media (37%); the self perceivedmost correct source was health professions (83.2%). Most ofthe teachers (81%) had not attended lecture about childrenfever. There were significant differences between marital status(p=.003), age (p= .000), whether had child or not (p= .017) andmain source of fever knowledge. Significant differences werefound between teachers had child or not (p= .030), age of theteacher (p= .008) and ever attended related lecture of childhoodfever. The average score of body temperature knowledge was6.37 and of fever management was 10.54. Different in maritalstature (p=.002)、had child or not (p =.004)、age (p=.048) andworking year (p=.004) had significant in score in feverknowledge. Teachers with age between 41-50 year old hadhigher score than those age between 21-30 year old (p= .007).Those with working year between 11-15 years (p = .002), withmain source of fever information (p= .002) and perceived mostcorrect source was health professions (p=.038) had the highestscore in knowledge about body temperature. Higher score intotal score of fever knowledge was those with health professionas the main source of fever information (p= .003). If the mainsource of fever knowledge was from health professions (p=.003) and those had joined lecture about fever (p=.000) had ahigher score in knowledge of body temperature.CONCLUSION: The result of this study showed thatinadequacy of fever knowledge among kindergarten teachers.The teachers perceived most correct information about feverwas from health profession. However, only 19% of the teachersreceived lecture about child fever. We suggested that healthprofession should provide more information to teacher ofkindergarten.[Keywords] fever, children, kindergarten teacher135

FP20-4INVESTIGATION OF THE PATHOGENY ANDCLINICAL CONDITIONS OF INFANTS HFMDIN CHANGCHUNSun Liwei,Li Lihong, Zhang Xiaojie,Tiian Yuling, DengLinfei, Wang Chengxun, He Yan, Zhao Yanling, LiuYuChangchun Children's Hospital, Changchun 130051, ChinaOBJECTIVE: Find out the pathogeny and the clinicalconditions of children’s hand-foot-mouth disease(HFMD) in ChangChun.METHOD: Isolate the virus of 530 HFMD childrenwith oropharyngeal swabs, which cellected fromchildren patients consulted in our hospital from May toNovember 2009, on RD cell line. Expand theenterovirus (EV), enterovirus 71 (EV71),and coxsackievirus A16 (CoxA16) of the samples withRT-PCR. Meanwhile, collect and analyse the meaterialsof epidemiology and clinical data.RESULT: We collected 530 samples of HFMDchildren and the homologous data. There were 387males and 143 females at the age of 27.84 ± 17.15months. The positive virus isolation was 166 caseswith the positive rate 31.32%; the PT-PCR EV positiverate was 32.61%, the EV71 positive rate was 9.57%,and the CoxA16 positive rate was 2.61%. And theclinical features were 66.7% with fever, 86.67% withskin rash, 29.41% with myocardial damage, and 7.14%with neurological complication. In laboratoryexamination, transaminase rised 17.64% and bloodglucose increased 29.41%, and the total white bloodcell count was 21.42×10 9 /L.CONCLUSIONS: The peak age of HFMD chilerenwas 27 months old in ChangChun. And the pathogenywas mainly EV, the following was EV71. The EV71infections mainly had neurological complication andthe CoxA16 infections were mainly with myocardialdamage.[Keywords]ChangChun, children, HFMDFP20-5CLINICAL AND ETIOLOGIC ASPECTS OFSEIZURES IN PEDIATRIC PRACTICEVinit Mehrotra 1 , Deepak Goel 2Biochemistry, Himalayan Institute of Medical Sciences 1 , Neurology, HimalayanInstitute of Medical Sciences 2 ,IndiaA seizure is defined as a paroxysmal, time limited change inmotor and or behavior that results from abnormal electricalactivity in the brain. Seizures are common neurologicaldisorder in pediatric group and occur in 3 to 5% of children.They are the most common cause for referral to pediatricpractices. So we undertook a study on various clinical andetiological aspects of seizures in children from neonatal to 5years of age. The present study was conducted over a period ofone year on 600 children who were admitted or OPD patientsof our hospital for the treatment of seizures.Out of total 45% were only diagnosed to have seizures either atthe time of presentation or during hospital stay or had a historyof seizure. Remaining (55%) were diagnosed for other diseasesand were been treated for seizures. This 55% were excludedfrom the study.It was observed that 31.25% seizures have been found to bemore common in the age group less than 3 years. Maximum45.95% had generalized seizures whereas partial seizures werepresent in 31.25% while remaining 22.79% children belongedto unclassified category. Among the generalized seizuresTonic-clonic seizures were the most common in 22.05%followed by clonic seizures in 11.02%. Absence seizure wasobserved in only 2.57%. Among 31.25% children havingpartial max 20.95% had complex partial seizure and simplepartial seizure was least common in 4.41%.The predominant type of seizure in age group 1 month to 1year was of clonic type in 11% where as in the age group 1year to 3 year complex partial seizure were observed in20.95%. Generalized tonic-clonic seizure was seen inmaximum number of children 17.6% between age group 3 yearto 5 year.It was also observed that the most common etiology wasidiopathic in 48.09% cases followed by head trauma in 11.42%and meningitis in 7.14% cases in all the age groups.In neonatal seizure single variety of seizures was observed in41.93% and the remaining had more than one type of seizures.The most common pattern of combined seizures was subtle andmulti-focal clonic. 67.74% new-born seizures occurred duringfirst 72 hours of life.Hypoxic Ischemic encephalopathy was the commonest causeof neonatal seizure and was observed in 50% of cases.[Keywords] Seizures, Pediatric practice136

FP20-6A STUDY OF REFRACTORY EPILEPSY INCHILDREN FROM 6 MONTHS TO 18 YRS OFAGETahir Mohd * , Singh R.P. ** , Rao Y.K. ***Department of Pediatrics,GSVM Medical College, Kanpur* Resident; ** Professor; ***LecturerOBJECTIVE: To evaluate etiology of refractoryepilepsy in children from 6 months to 18 years of age.METHOD: A hospital based cross sectional study wasconducted in Children Hospital Epileptic Clinic Deptt.of Pediatrics and neurology unit of K.P.S. Institute ofMedicine, GSVM Medical College Kanpur for a periodof 21 months (Between Jan 08 to Sept 09). All epilepticpatients between age of 6 months to 18 years of agewhich were not responding to two first lineanticonvulsants drugs were enrolled in our study andwas subjected to detailed clinical history, family historyand onset of seizure, number of seizure type, frequencyof seizure, febrile status, mental retardation,developmental delay. History of perinatal brain injuryduration of labour, gestational history, perinatal history,post natal history, developmental history, type ofseizure, onset of seizure, number of seizure, history oftrauma, neurodegenerative disorder, infection. Eachcase was also subjected to thorough physicalexamination including detailed neurologicalassessment. Patients were investigated for sepsisscreen, CT scan, MRI scan, CSF examination, EEG,blood sugar levels, kidney profile, serum electrolyteand all heading were under working proforma.MAIN RESULT: The cause of refractory epilepsy inour study were cerebral infection 33%, Perinatalasphyxia 20%, demyelinating disorders 8%,cerebrovascular accidents were comprising 3%. Allcases of refractory epilepsy due to perinatal asphyxiawere found between age group of 6 months to 6 years.CONCLUSION: The cause of refractory epilepsy wasfound in 60% of cases and most common cause wascerebral infection 33% followed by perinatal asphyxia20%. In 40% cases of refractory epilepsy there were noidentifiable cause could be found and were termed asIdiopathic type of refractory epilepsy.MS9-01RECENT ADVANCE IN CONGENITALMUSCULAR DYSTROPHYIchizo NishinoDirector, Department of Neuromuscular Research, National Institute ofNeuroscience, National Center of Neurology and Psychiatry (NCNP), JapanCongenital muscular dystrophy (CMD) is defined as musculardystrophy with neonatal or infantile onset. One of the mostimportant facts about CMD is that the frequency of subtypeswide varies widely among different ethnic groups. Forexample, in Japan, Fukuyama CMD (FCMD), which is due toFKTN mutations, accounts for 50% of the cases while only fewcases with FKTN mutations were documented in Europeancountries. In contrast, merosin-negative CMD accounts fornearly half of the cases in European countries, and probablyfollowed by MDC1C, both of which are very rare in Japan.Because of this peculiar nature of CMD occurrence, theclassification of the CMD is different between Japan andEuropean countries. In European countries, CMD is classicallyclassified into merosin-negative CMD and merosin-positiveCMD while in Japan it is grouped into FCMD and nonFCMD.Therefore, this situation serves as a caveat to other countriesand regions and warrants the need to consider local statisticaldata about CMD for establishing the appropriate classification.Both FCMD and MDC1C are caused by defectiveglycosylation on α-dystroglycan, thereby they are collectivelycalled α-dystroglycanopathy. As laminin interacts with thesugar chains of α-dystroglycan, the binding between lamininand alpha-dystroglycan is loosened, resulting in the fragility ofthe sarcolemma.Another important CMD is Ullrich disease. This disease iscaused by mutations in any of the three genes that encodecollagen VI. In terms of muscle histology, two forms arerecognized: complete collagen VI deficiency andsarcolemma-specific collagen VI deficiency (SSCD). Theformer is caused by recessive mutations while the latter bydominant mutations in the triple helical domain. Majority ofpatients have SSCD form. Interestingly, in contrast to FCMD,MDC1C and merosin-negative CMD, the frequency of Ullrichdisease seems to be similar among different ethnic groups. Thisis most likely because the major form of Ullrich CMD, SSCD,is caused by de novo mutation in the collagen VI genes ratherthan by common ancestral mutations.In my talk, I will mainly cover α-dystroglycanopathy andUllrich disease[Keywords]refractory epilepsy, perinatal asphyxia, cerebralinfection ,children137

MS9-04PERSPECTIVE ON CLINICAL TRIALS INSPINAL MUSCULAR ATROPHYYuh-Jyh JongProfessor, Graduate Institute of Medicine, College of Medicine,Kaohsiung Medical University, JapanMS10-01KAWASAKI DISEASE IS A DISORDER CAUSEDBY BACTERIA IN THE GASTROINTESTINALTRACTY. Yamashiro,M.D.,Ph.DJuntendo University, Tokyo, JapanSpinal muscular atrophy (SMA) is an autosomalrecessive disease characterized by degeneration of theanterior horn cells of the spinal cord which leads tomuscular paralysis and muscular atrophy and theleading genetic cause of infant mortality. SMA isclassified into type I, II, III according to the age ofonset and progression of the disease. The causativegene, survival motor neuron (SMN), has two copiesSMN1 and SMN2, with 99% identical sequence. Acritical nucleotide difference at position 6 in exon 7 ofSMN2, C to T, causes alternative splicing in pre-mRNAand consequently results in a considerable amount oftruncated mRNA with the lack of exon 7, while SMN1expresses exclusively full-length transcript. All SMApatients are effectively null for SMN1 but retain at leastone copy of SMN2, indicating SMA is generated by afall in the level of full-length SMN protein and thelevel expressed by the retained SMN2 might control theseverity. Accordingly, sodium butyrate was firstly toshow effectively to increase the amount of full-lengthSMN protein in SMA lymphoid cell lines by changingthe alternative splicing pattern of exon 7 in the SMN2gene and ameliorating SMA symptoms in SMA-likemice in 2001.Kawasaki disease (KD) is an acute multisystemvasculitis of unknown etiology that primarily affectsyoung children and predominantly involve the coronaryarteries.We previously suggested that gut bacteria may beinvolved in the onset of KD. In this study we haveevaluated the production of heat-shock proteins (HSP)and superantigens (sAgs) by microorganisms isolatedfrom the jejunal mucosa of 19 children with KD childrenin the acute phase and 15 age-matched control children.We found 13 strains of Gram-negative microbes frompatients with KD which produced large amounts of HSP60 and induced proinflammatory cytokine production byperipheral blood mononuclear cells. The Gram-negativemicrobes also elicited endogenous HSP 60 production,leading to anti-inflammatory IL-10 secretion. We alsoidentified 18 strains of Gram-positive cocci which hadsuparantigenic properties and which induced theexpansion of Vb2 T-cells in vitro. All of the bacteriawere antibiotic-resistant. These data strongly suggestthat sAg and HSP productions by gut bacteria might beinvolved in KD.Since then, some drugs, compounds or small moleculesincluding sodium butyrate, trichostatin A,suberoylanilide hydroxamic acid (SAHA) , benzamideM344, phenylbutyrate, hydroxyurea, valproic acid,aclarubicin, 5-(N-ethyl-N-isopropyl)-amiloride (Na + /H +exchanger inhibitor), polyphenol botanical compounds,geneticin and 2,4-diaminoquinazoline derivatives havebeen used in SMA-like mice, SMA patients' fibroblasts,lymphoid cell lines or SMA patients, with someshowing effective results either in terms of elevation ofSMN2 expression in cell lines or improving musclestrength, lung function, and increasing SMN2 geneexpression in SMA patients. We will overview thechallenges and opportunities, current and futuretherapeutic strategies, and progress to date in clinicaltrials including valproic acid, phenylbutyrate,hydroxyurea, riluzole, gabapentin, albuterol andsomatotropin in SMA.139

MS10-02PATHOGENESIS OF PANDEMIC H1N1YU-LUNG LAUProfessor, The University of Hong Kong, Hong KongThe pandemic influenza A H1N1 (pdm H1N1) emergedin California and Mexico in April 2009. There wasinitial fear that the case fatality rate (CFR) could be 2%as reported in Mexico, but now it is clear that the pdmH1N1 causes a disease no more severe than seasonalinfluenza with a CFR between 0.1 to 0.2%. However itcould cause serious morbidities and deaths in pregnantwomen, obese persons and patients with chronicunderlying disease.Early animal studies using ferrets, mice and macaquesof pdm H1N1 infection suggest more severe illnesscompared with seasonal influenza, although much lessvirulent than H5N1 or the 1918 pdm Spanish flu virus.However later studies using human immune cells andrespiratory epithelial tissues ex vivo suggest similarcapacity of pdm H1N1 for cytokine induction asseasonal influenza virus, but differs in its ability toreplicate in human conjunctiva. Post-mortem studies ofpatients died from pdm H1N1 revealed tracheitis,bronchiolitis and diffuse alveolar damage. Viral antigenwas seen most commonly in the epithelium oftracheobronchial tree. Marked expression of TLR-3and IFN-γ, with CD8 + T cells and granzme B + cellswere noted in the lung, with no evidence of viraldissemination outside the lung. Evidence of secondarybacterial superinfection with Streptococcuspneumoniae and Staphylococcus aureus was common.Susceptibility to pdm H1N1 is less in elderlies over 65years old than the younger population because of theirhigher prevalence of cross-reacting antibodies. Theoverall mild disease severity of pdm H1N1 influenzamay be related to pre-existing T-cell memory due to theconservation of a large fraction of T-cell epitopesbetween seasonal influenza and pdm H1N1. There isalso some evidence to suggest people deficient in IgG2may be more susceptible to pdm H1N1.We areinterested in defining cross-reacting T cell responses aswell as the role of mannose binding lectin in pdmH1N1.MS10-03CLINICAL FEATURES AND HOUSEHOLDTRANSMISSION OF NOVEL INFLUENZA (H1N1)IN CHILDRENLuan-Yin CHANGAttending Physician, Division of Pediatric Infectious Disease, Department ofPediatrics, National Taiwan University Hospital, TaiwanFrom July 24, 2009 to Dec 4, 2009, we collected cases infectedwith 2009 novel H1N1. Their demographics, underlyingmedical conditions, clinical data, receipt of antiviral therapy,need for intensive care and outcome were analyzed to findclinical features and risk factors of hositalization and severeinfections.The risk factors associated with hospitalization were age lessthan 1 year old and underlying disease includingcardiovascular disease, hematological and oncological disease,and immunosuppression host. Of the inpatients, obesity,dyspnea, C-reactive protein (CRP) >3 mg/dL, having pleuraleffusion, and delayed antiviral therapy were significantlyassociated with the need of intensive care and/or death.Cautious monitoring of these parameters and early treatmentmay improve the outcome.We also enrolled novel H1N1 patients and their householdmembers to undergo clinical evaluations, virological studiesand questionnaire-based interviews between August 2009 andNovember 2009. Novel H1N1 virus infection was defined aseither positive H1N1 RT-PCR or serum hemagglutinininhibition (HAI) titer ≥1:40. Clinical manifestations andoutcomes were analyzed and household transmission rate wascalculated. Eighty seven families including 87 index cases and223 household members were enrolled. The mean (SD) age ofindex cases was 10.6 (7.2) years and that of household contacts33.8 (17.9) years. The overall novel H1N1 virus transmissionrate to household contacts was 27% (60/223): 61% (35/57) tohousehold children and 15% (25/166) to household adults. Thetransmission rates were 63% (35/56) for siblings, 14% (20/138)for parents, 22% (4/18) for grandparents, and 20% (1/5) foruncles and aunts, respectively (p

Sunday 18 AprilFP21-1LOWER MIR-146A AND MIR-155 EXPRESSIONIN ATOPIC DERMATITISChien-Fu Chen 1 , Chiang BL Chiang 21 Department of Pediatrics of Buddhist Tzu Chi Dalin General Hospital, Chiayi,Taiwan; 2 Department of Pediatrics, National Taiwan University Hospital,Taipei, TaiwanOBJECTIVE: The mechanism of atopic dermatitis (AD)may be the gene dysregulation of both the innate and theadaptive immune systems. MicroRNAs (miRNAs) whichdownregulate gene expression by binding to messenger RNAmay be quite common in human diseases. This study is toevaluate whether there is any special miRNA expression inthe peripheral blood of children with AD in Taiwan.METHODS: 87 Taiwanese children (2–14years) areevaluated including 24 healthy children, 33 patients with ADand 30 only airway allergic children (allergic rhinitis and/orasthma). We choosed five miRNAs(miR-146a,miR-148a,miR148b, miR-152, miR-155) which may beassociated with atopic dermatitis 、 asthma 、 IgE or theregulation of Th1/Th2 pathway in recent studies. Theexpression levels of these five miRNAs of total leukocytes inperipheral blood were obtained from TagMan MicroRNAassays.Serum total IgE / specific IgE were detected byPharmacia CAP, serum IFN-r level by DuoSet ELISA andserum IL-4 level by Quantikine HS 400.MAIN RESULTS: Children with AD had significantlylower miR-146a and miR-155 expression as compared withhealthy children (P = 0.003; P = 0.043). These two miRNAsexpression maybe has no significant correlation with theseverity or course of AD. Children with asthma hadsignificantly lower miR-146a expression (P = 0.031), butasthma maybe had no significant effect in miR-146aexpression of children with AD.MiR-146a and miR-155expression had a significantly negative correlation with totalIgE (r = -0.220, P = 0.044; r = -0.255, P = 0.020. two-tailed).MiR-155 expression was significantly associated with serumspecific IgE to D.p (P = 0.024) or D.f (P = 0.049). MiR-148a,miR-148b or miR-152 expression had no significantcorrelation with AD.CONCLUSION: Our study is the first report that miR-146aand miR-155 expression of total leukocytes in peripheralblood were strongly associated with atopic dermatitis.Children with atopic dermatitis had significantly lowermiR-146a and miR-155 expression. Although the mechanismof this interaction is still unknown, Our result suggests thatmiR-146a and miR-155 maybe negatively regulate geneexpression to suppress atopic dermatitis.[Keywords] microRNA, Atopic DermatitisFP21-2CAFFEIC ACID PHENETHYL ESTER INHIBITSNUCLEAR FACTOR-κB AND PROTEIN KINASEB SIGNALLING PATHWAYS AND INDUCESCASPASE-3 EXPRESSION IN PRIMARY HUMANCD4 + T CELLSLi-Chieh Wang, Bor-Luen ChiangDepartment of Pediatrics, National Taiwan University Hospital, TaiwanOBJECTIVE: Caffeic acid phenethyl ester (CAPE), anactive component in propolis, is known to haveanti-tumor, anti-inflammatory and antioxidant properties.CAPE has been reported to attenuate airwayhyperresponsiveness (AHR) in murine model of asthma.In this study, the effects of CAPE on the functions ofprimary human CD4 + T cells from healthy subjects andasthmatic pateints were evaluated in vitro.METHODS: The primary human CD4 + T cells wereisolated from healthy subjects and mite-sensitizedasthmatic pateints by autoMACS. The CD4 + T cells werestimulated by soluble anti-CD3 and anti-CD28monoclonal antibodies (mAbs) in the absence andpresence of CAPE for 48 hours. The cytokine levels inthe supernatants were evaluated by ELISA and thelymphoproliferation was checked by tritiated thymidineincorporation method. The signaling pathways includingnuclear factor (NF)-κB, protein kinase B (Akt) and p38mitogen-activated protein kinase (MAPK) pathwayswere evaluated by Western blot. Besides, we cultured theprimary human CD4 + T cells with CAPE for 12 hours toanalyze the active caspase-3 expression by intracellularstaining and flow cytometry.MAIN RESULTS: CAPE significantly suppressedinterferon (IFN)- and interleukin (IL)-5 production andproliferation of CD4 + T cells stimulated by solubleanti-CD3 and anti-CD28 mAbs both in healthy subjectsand asthmatic patients. CAPE inhibited NF-κBactivation and Akt phosphorylation, but not p38 MAPKphosphorylation in T cells. CAPE also induced activecaspase-3 expression in CD4 + T cells; CCR4 + CD4 + Tcells were more sensitive to CAPE induction thanCXCR3 + CD4 + T cells.CONCLUSION: These results indicate that CAPEinhibits cytokine production and proliferation of T cells,which might be related to the NF-κB and Akt signalingpathways, and that CCR4 + CD4 + T cells are moresensitive to CAPE inhibition. This study provides a newinsight into the mechanisms of CAPE for immuneregulation and a rationale for the use of propolis for thetreatment of allergic disorders.141

FP21-3SODIUM SULFITE ENHANCES MITEALLERGEN INDUCED AIRWAYINFLAMMATION AND SERUMIMMUNOGLOBULIN E PRODUCTION IN THEMURINE MODEL: THE ROLE OF DAMAGE OFAIRWAY EPITHELIAL TIGHT JUNCTIONSHeng-Kuei Lin 1 , Lin-Shien Fu 2Pediatrics, Taichung Veterans General Hospital, Taiwan 1 , Department ofPediatrics, Taichung Veterans General Hospital, Taiwan 2BACKGROUND: Sulfur dioxide is a typical airpollutant. Sulfites, which are formed at the bronchialmucosa from inhaled sulfur dioxide, might play a rolein the exacerbation of asthma. We investigated theeffects of sodium sulfite and its interaction with ahouse dust mite (Dermatophagoides pteronyssinus, Derp) on airway inflammation.METHODS: BALB/c mice were divided into fourgroups: control, mite intranasal (mIN), sodium sulfiteintranasal (sIN) and mIN+sIN. In non-control groups,the mice were sensitized twice with mite allergensubcutaneously. Mite allergen was then administratedintranasally for eight days in the mIN and mIN+sINgroups. Sodium sulfite was administrated in the sINand mIN+sIN groups intranasally for 22 days.Immunohistochemical staining, histopathology andcytokine levels were analysed.RESULTS: In comparison with the control group, theperibronchiolar, alveolar and total inflammatory scoreswere increased in the mIN+sIN group (p

FP21-55-AZACYTIDINE ENHANCES CONVERSIONOF PERIPHERAL BLOOD CD4+CD25- T CELLSTO CD4+CD25HIGHFOXP3+ REGULATORY TCELLSSyh-Jae Lin 1 , Chun-Hao Lu 2 , Dah-Chin Yan 1 ,Cheng-Jang Wu 2 , Cheng-Chi Chan 2 , Jing-Long Huang 1and Ming-Ling Kuo 21 Department of Pediatrics, Chang Gung Children's Hospital and Chang GungUniversity, Taoyuan, Taiwan; 2 Department of Microbiology and Immunology,Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan,TaiwanFOXP3 is a master transcription factor for thehomeostasis of CD4+ T regulatory (Treg) cells.Epigenetic regulation of FOXP3 expression hasrecently been demonstrated to be important for thedevelopment and suppressive function of Treg cells.However, the induction of human Treg cells throughepigenetic manipulation has not been reported. In thepresent study, We established that (1) 5-azacytidine(5-Aza), a DNA methyltransferase inhibitor resulting inDNA hypomethylation, enhanced conversion of humanperipheral blood CD4+CD25- T cells toCD4+CD25highFOXP3+ T cells under suboptimalstimulation; (2) 5-Aza resulted in enhanced interleukin(IL)-2, but decreased IL-10 production fromCD4+CD25- T cells but did not affect levels ofinterferon (IFN)-γ, and transforming growth factor-β(TGF-β); (3) 5-Aza-induced CD4+CD25high T cellsexpressed higher FOXP3, CTLA-4 and GITR, and hadhigher suppressive activity compared with the cellssorted from activated T cells without 5-Aza treatment.(4) The inhibition of the proliferation of responderCD4+ T cells was contact –dependent. Taken together,The 5-Aza-converted Treg cells behave similarly tonatural occurring Treg, and may serve as a valuabletool for studying the gene regulation and foridentifying specific surface markers for nTreg. Ourresults have significant implication for using epigeneticstrategy to generate functional Treg cells for clinicalapplication.FP21-6THE ASSOCIATION BETWEEN MULTIPLEPARAMETERS AND HIGH-RISK ASTHMA INCHILDREN WITH ATOPIC ASTHMAChieh-Han Cheng, Shyh-Dar Shyur, Szu-Hung Chu,Li-Hsin Huang, Yu-Hsuan Kao, Wei-Te Lei, Chia-Yi Lo,Kuo-Hsi Lee, Chen-Kuan Chen, Ling-Chun LiuDepartment of Pediatrics, Mackay Memorial Hospital, Taipei, TaiwanOBJECTIVE: Many of the asthma deaths occur inotherwise healthy young productive individuals. Manyof these deaths were almost certainly preventable ifpatients were treated more aggressively for their asthma.It is important to establish an asthmatic’s risk for seriousadverse outcomes. Hence, we try to seek the associationbetween multiple allergic parameters and high-riskasthma in children with atopic asthma. These clinicalassessment tools will allow for better individualizedtherapy for asthma patients.METHODS: Children aged 5-17.6 years-old whomdiagnosed with atopic asthma were enrolled. Patientswhom had atopic asthma were defined as patients withdiagnosis of asthma also had specific IgE positive to anyone of the eight allergens with class levels ≧1,(including D.pteronyssinus, D. farinae, cat dander, dogdander, cockroach, egg, milk and fish). High-risk asthmawas defined as asthma requiring admission to a hospitalor a visit to an emergency department. We try to find outthe association between allergic parameters (asthmaseverity, asthma score, CAP test, total IgE level,eosinophil count and pulmonary function) and high-riskasthma.MAIN RESULTS: Total 403 children diagnosed withatopic asthma were enrolled. We found there wassignificant association between some allergic parametersand high-risk asthma (including asthma severity, asthmascore, specific IgE to D.p., specific IgE to D.f., andFEF 25-75% ). People with higher asthma severity, higherasthma score, allergy to D.p., allergy to D.f, and lowerFEF 25-75% are high-risk asthma groups.CONCLUSIONS: Through these allergic parameters,we could find out the high risk asthma groups.Therefore, we may pay more attention in these high riskpatients, and make our therapy toward asthma better inclinical practice.[Keywords] high risk asthma, atopic asthma143

FP21-7THE CORRELATION BETWEEN BMI ANDVARIOUS PARAMETERS IN ASTHMATICCHILDREN IN TAIWANWei-Te Lei, Shyh-Dar Shyur, Szu-Hung Chu, Li-HsinHuang, Yu-Hsuan Kao, Chia-Yi Lo, Chieh-Han Cheng,Kuo-Hsi Lee, Chen-Kuan Chen, Ling-Chun LiuDepartment of Pediatrics, Mackay Memorial Hospital, Taipei, TaiwanOBJECTIVE: The pathophysiology and risk factors ofasthma are various. Overweight maybe one of those riskfactors in recent studies. There are some evidences of anassociation between excess body weight or obesity andatopy--particularly asthma. The prevalence of overweightwas significantly higher in children with moderate to severeasthma than in their peers, and being overweight wasassociated with significantly more severe asthma symptoms.Our study aims on the correlation between BMI and variousparameters in children with atopic asthma.MATERIALS AND METHODS: 1142 children (706 males(61.8%), 436 females (38.2%)) aged from 5-17 year-old(mean age: 8.16 year-old) diagnosed of mid intermittent tosevere persistent asthma were enrolled. We divided them into3 groups according to the BMI (Growth Charts of TaiwaneseYouth: Norms Based on Health-Related Physical Fitness,MTJM 2003; 8 (Supplement 2):s84-92, revised on 2007):overweight (BMI≧85%), normal weight (BMIC: p=0.004); FEF25-75%(A>C: p=0.028), asthma symptom score (A>C: p=0.038),specific IgE for milk (AC:p=0.07). There was no statistically significant relation ofasthma severity, ever been to ER or admission, specific IgEfor D.p, D.f, cat dander, dog dander, cockroach, fish, and age.CONCLUSION: In children aged 5-17 year-old withoverweight, they got more severe asthma symptoms butbetter pulmonary function in both large and small airway.[Keywords] BMI, asthma, childrenFP22-1LACTOBACILLUS RHAMMOSUS GGENHANCES PROTECTION AGAINSTLIPOPOLYSACCHARIDE IN VITROShu-Ting Chang 1,2 , Hung-Chang Lee 1 , Jen-Shiu ChiangChiau 3 , Chun-Yan Yeung 1 , Shiuh-Bin Fang 4 , Wai-TaoChan 1 , Chuen-Bin Jiang 1 , Mei-Lien Cheng 3 , Hsu-WeiFang 5,61 Department of Paediatrics, Mackay Memorial Hospital, Taipei, Taiwan2 Department of Pediatrics 2 , Taiwan Advantist Hospital, Taipei, Taiwan3 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan;4 Centre for Paediatric Gastroenterology, Royal Free Hospital and UniversityCollege Medical School, London, UK; 5 Department of Chemical Engineeringand Biotechnology, National Taipei University Technology, Taipei, Taiwan;6 Division of Medical Engineering Research, National Health Research Institutes,Miaoli, TaiwanOBJECTIVE: Probiotics are considered to effect in reducinggut inflammation induced by pathogens. Recent studies ofmurine models suggest that probiotic may prevent disease ofmucosal inflammation. We have previously shown thatLactobacilli provide anti-inflammation in vitro. The objectiveof this study was to investigate whether Lactobacillusrhamnosus GG (LGG) protected intestinal Caco-2 cells beforeexposed to Salmonella enterica serotype typhimuriumlipopolysaccharide (LPS) by modulate immune response.METHODS: In polarized Caco-2 cells, LGG (1x10 5 /ml) wasadded by various time courses (1, 6 or 24 hours) then wash outLGG before exposed to LPS for 3 hours. To identifyinflammatory response induced by LPS that those Caco-2 cellswere investigated employing quantitative RT-PCR. LGGdown-regulate gene expression of interleukin-6 (IL-6), IL-8,IL-10 and IL-12 after 6 hours.MAIN RESULTS: The data was shown that chemokine IL-6and acute inflammation IL-8 gene expression was absolutelyinhibited after 24 hours culture. At the mean time, we foundthat IL-6 and IL-8 gene expression have time dependdecreasing. IL-10 and IL-12 gene expression weredown-regulated after 6 hours. Interested, gene expression ofpre-inflammation IL-10 and Th1 IL-12 was not effected byadded LGG without LPS. The role of Th3 TGF-beta1 isimmunomodulation in Th phenotype profile and foundup-regulated gene expression at each time points after addedLGG.CONCLUSION: The capacity of LGG in reducing stimulationof LPS is by immunomodulate effects. Pretreatment of LGGmight increase the protection of intestinal cells against damageinduced by LPS during infections and inflammation. This studyhelps us to understand the underlying mechanisms in thefuture.[Keyword] Lactobacillus; Caco-2; protection; Salmonellalipopolysaccharide; immunomodulation144

FP22-2USE OF A FAST AND EFFICIENT CO-CULTUREMODEL TO EVALUATEANTI-INFLAMMATORY ANDBARRIER-REINFORCING EFFECTS OFCOMMERCIAL LACTOBACILLUS STRAINSChow-Hong Tay 1,2 , Hung-Chang Lee 2 , Jen-Shiu ChiangChiau 3 , Chun-Yan Yeung 2 , Shiuh-Bin Fang 4 , Wai-TaoChan 2 , Chuen-Bin Jiang 2 , Mei-Lien Cheng 3 , Hsu-WeiFang 5,61 Department of Pediatrics, Sin-Lau Hospital, Tainan, Taiwan; 2 Department ofPediatrics, Mackay Memorial Hospital, Taipei, Taiwan; 3 Department ofMedical Research, Mackay Memorial Hospital, Taipei, Taiwan; 4 Centre forPediatric Gastroenterology, Royal Free Campus, University College LondonMedical School, London, UK; 5 Department of Chemical Engineering andBiotechnology, National Taipei University Technology, Taipei, Taiwan;6 Division of Medical Engineering Research, National Health ResearchInstitutes, Miaoli, TaiwanOBJECTIVES: Lactobacilli have beneficial effects on intestinalinflammation in murine models or clinical trials. However, theseevidences can be efficiently and accurately evaluated in vitro. Aco-culture model mimicking mucosal immune responses isdeveloped and utilized in investigation of the interactionsbetween bacteria, enterocytes, and leucocytes. The aim of thisstudy was to set up an inflamed co-culture model to evaluate theanti-inflammatory and barrier-reinforcing effects ofLactobacillus strains.METHODS: Using the transwell co-culture model, Salmonellalipopolysaccharide (LPS) was apically added to polarized Caco-2cells co-cultured with peripheral blood mononuclear cells(PBMCs) in the basolateral compartment. Various Lactobacillusstrains (Lactobacillus casei rhamnosus (Lcr35), L. rhamnosusGG (LGG), L. rhamnosus, and L. johnsonii) were added onCaco-2 cells in inflamed system for 1 hour, 6 hours, or 24 hours.MAIN RESULTS: Apical inoculation of all Lactobacillusstrains significantly inhibited the apical and basolateral secretionof interleukin-8 (IL-8) after 24 hours. The quantitative mRNAexpression analysis showed that all Lactobacillus strains exceptfor L. johnsonii, significantly down-regulated gene expression ofIL-8 in Caco-2 cells and PBMCs. Compared tonon-lactobacilli-treated controls, transepithelial electricalresistance of the polarized Caco-2 cell monolayers co-culturedwith LGG, L. rhamnosus or L. johnsonii was significantlyincreased after 24 hours post LPS pretreatment. Lactobacilliexhibited strain-specific inhibition upon LPS induced IL-8secretion and mRNA expression on basis of significantdifferences from negative controls.CONCLUSION: We suggest that certain Lactobacillus strainscan exert anti-inflammatory effects and ameliorate barrierdysfunction in the Salmonella LPS-pretreated inflamed intestinalepithelium in vitro. Our proposed Caco-2/PBMCs co-culturemodel is not only a useful in vitro system to evaluate immuneresponses and gut integrity after enteric infection orinflammation, but also a feasible platform to screen lactobacillitherapeutic agents for further animal studies and clinical trials.[Keywords] Lactobacillus; Caco-2; peripheral blood mononuclearcells; Salmonella lipopolysaccharide; transepithelial electricalresistanceFP22-3PROBIOTICS HASTEN FECAL ELIMINATIONOF SALMONELLA IN CHILDREN’SNON-TYPHOID SALMONELLA ENTERITISHsun-Chin Chao, Shih-Yen Chen, Chien-Chang Chen,Man-Shan Kong, Ming-Wei LaiDivision of Gastroenterology, Department of Pediatrics, Chang Gung Children’sHospital, Chang Gung University College of Medicine, 5 Fu-Hsin Street,Kuei-Shan, Taoyuan 33305, TaiwanOBJECTIVES: To evaluate the effect of probiotics onfecal excretion of Salmonella in pediatric Non-typhoidSalmonella enteritis.METHODS: We conducted a 3-year randomized trial ofprobiotics treatment, Lactobacillus casei rhamnosus orBio-three (Streptococcus fecalis, Bacillus mesentericus,Clostridium butyricum) in children with non-typhoidSalmonella enteritis (P group). The dosage of probioticsadministrated was 5-10 x 10 8 cfu/day. Those childrenwithout probiotics treatment were enrolled as control(NP group). The subject enrolled were those patients(age, 3-60 months) with positive stool culture fornon-typhoid Salmonella and in whom stool cultures werefollowed regularly every 2 weeks until repeatednegative results obtained. Those patients received orrequired antibiotic therapies were excluded. Thedifferences in the elimination of fecal Salmonellabetween P and NP groups were compared.MAIN RESULTS: Study population consisted of 211patients (107 males, 104 females, mean age of 2.34 ±1.45 years). There was significant difference in the rateof elimination between P (n=145) and NP (n=66) groups.The cumulative elimination rate at 4-, 8-, and 12-weeksin P group was 51.7 %, 82.8 %, and 95.8 %, which wasall significantly (p

FP22-4DIFFERENT PRESENTATIONS OFMECKEL’S DIVERTICULUM IN DIFFERENTAGEJeng-Jung Chen 1 , Hung-Chang Lee 1 , Chun-Yan Yeung 1 ,Wai-Tao Chan 1 , Chuen-Bin Jiang 1 , Jin-Cherng Sheu 2,Nein-Lu Wang 2Department of Pediatrics 1, Department of Pediatric Surgery 2 , MackayMemorial Hospital, Taipei, TaiwanOBJECTIVE: Meckel’s diverticulum is the mostcommon congenital malformation of gastrointestinaltract. The purpose of this study is to understand theclinical features of Meckel’s diverticulum in differentage in order to remind an early diagnosis.METHODS: We collected the patients of Meckel’sdiverticulum diagnosed at Mackay Memorial Hospitalin Taiwan from 1984 to 2009. After chart review, thesepatients were grouped by different age (18 years-old).The clinical features of Meckel’s diverticulum wererecorded and analyzed.MAIN RESULTS: Totally, 128 patients were includedin this study, including 91 males and 37 females. Thirtypercent of patients were diagnosed before 2 years-old.And 63% of the Meckel’s diverticulums were found inthe first decade of life. Fifty-five percent of patientswere symptomatic, and 45% of Meckel’s diverticulumswere found incidentally during surgery for otherdiseases. Gastrointestinal hemorrhage occurredpredominantly in patients age less than 18 years.Diverticulitis with or without perforation was found in76% of symptomatic patients age more than 18years-old. Among all patients, only 7% of Meckel’sdiverticulums were presented as painlessgastrointestinal bleeding. When the Meckel’sdiverticulums were lined by an ectopic gastric mucosaor pancreas, 75% of patients are symptomatic. In theasymptomatic patients, only 14% of Meckel’sdiverticulums were found an ectopic gastric mucosa orpancreas inside.CONCLUSION: Although painless lower GI bleedingwas thought to be the typical presentation of Meckel’sdiverticulum, there are only 7 % in this series. Inpediatric population (age < 18 years-old), most ofsymptomatic Meckel’s diverticulums presented asgastrointestinal hemorrhage with or without abdominalpain. But in the adult group (age > 18 years-old), themost common complication was diverticulitis with orwithout perforation.FP22-5CHILDHOOD CONSTIPATION IN TAIWAN: ANATIONWIDE SURVEYPo-Hung Chen 1,3 ,Tzee-Chung Wu 1,3 , Liang-KungChen 2,3 , Ren-Bin Tang 1,3 , Wen-Han Pan 4 , Li-TeWu 1,5 , Frank E. James 51 Children’s Medical Center, 2 Department of Family Medicine, Taipei VeteransGeneral Hospital,Taiwan; 3 National Yang Ming University School of Medicine,Taiwan; and 4 Division of Epidemiology and Genetics, Institute of BiomedicalSciences, Academia Sinica, Taipei, Taiwan, 5 University of Washington School ofPublic Health and Community Medicine the United States of AmericaOBJECTIVE: To evaluate the prevalence andassociated factors of childhood constipation in Taiwan.DESIGN: Retrospective, case-based interview.SETTING: A nationwide study with complexmulti-staged sampling strategy.PARTICIPANTS: 2419 healthy children aged 7-12years in Taiwan.INTERVENTIONS: None.MAIN OUTCOME MEASUREMENTS: Prevalenceof constipation and associated factors (e.g. demographicdata and dietary history).RESULTS: In total, 2419 individuals (1296 boys and1123 girls, mean age=9.3±2.2 years) were interviewedwith a response rate of 96.9%. The prevalence ofconstipation was 32.7% and girls were more likely tohave constipation than boys (36.8% vs. 29.0%, P=0.001)in this study. The prevalence of constipation wasinversely related to age (24.9% for children aged 11 and12, 34.0% for children aged 9 and 10, and 39.6% forchildren aged 7 and 8, P

FP22-6ADIPONECTIN-MEDIATED HEMEOXYGENASE-1 INDUCTION PROTECTSIRON-INDUCED LIVER INJURY VIA APPARΑ-DEPENDENT MECHANISMChun-Hsien Yu 1 , Heng Lin 2 , and Shu-Hui Juan 31 Department of Pediatrics, Tzu-Chi General Hospital, Taipei Branch, Taipei,and Tzu-Chi University College of Medicien, Hualien, Taiwan;2 Institute ofPharmacology and Toxicology, Tzu-Chi University, Hualien, Taiwan;3Graduate Institute of Medical Sciences and Department of Physiology, TaipeiMedical University, Taipei, Taiwan.Protective effects of adiponectin (APN) were shownagainst various oxidative challenges; however, itstherapeutic implications and the mechanismsunderlying hepatic iron overload remain unclear.Herein, we show that the deleterious effects of irondextran on liver function and iron deposition weresignificantly reversed by adiponectin gene therapy,which was accompanied by AMP-activated proteinkinase (AMPK) phosphorylation and heme oxygenase(HO)-1 induction. Furthermore, AMPK-mediatedperoxisome proliferator-activated receptor-α(PPARα)activation by APN is ascribable to HO-1 induction.Additionally, we revealed a direct transcriptionalregulation of HO-1 by the binding of PPARα to aPPAR-responsive element (PPRE) by variousexperimental assessments. Interestingly,overexpression of HO-1 in hepatocytes mimicked theprotective effect of APN in attenuating iron-mediatedinjury, whereas it was abolished by SnPP (HO-1inhibitors) and small interfering HO-1. Furthermore,the end-product of the HO-1 reaction, bilirubin, but notCO, protected hepatocytes from iron dextran-mediatedcaspase activation.CONCLUSIONS: We demonstrate a novel functionalPPRE in the promoter regions of HO-1, andAPN-mediated HO-1 induction elicited anantiapoptotic effect and a decrease in iron deposition inhepatocytes subjected to iron challenge.[Keywords] Hepatic iron overload, Adiponectin, AMP-activatedprotein kinase, peroxisome proliferator-activated receptor-α, Hemeoxygenase-1FP22-7REDUCED BRAIN CONTENT OF ARACHIDONICACID AND DOCOSAHEXAENOIC ACID ISRELATE TO THE SEVERITY OF LIVERFIBROSISChih-Cheng Chen 1 , Li-Tung Huang 2 , You-Lin Tain 3 , M.Y.Chung 4 , F.S. Chen 5 , Hsin Chun Huang 6 , C.A. Liu 7 , M.J.OY 8 , P.H. Chao 9 , H.C. Huang 10Pediatrics,Chang Gung Memorial Hospital, Kaohsiung Medical Center, Taiwan 1 ,Pediatrics, Chang Gung Memorial Hospital, Taiwan 2 , Pediatrics,Chang GungMemorial Hospital, Kaohsiung Medical Center, Kaohsiung, Taiwan 3 , Pediatrics,Chang-Gung Memorial Hospital-Kaohsiung Medical Center, Pediatrics 4, 5, 6, 7, 8, 9 ,Department of Veterinary Medicine, National Pingtung University of Science andTechnology, Taiwan 10BACKGROUND: Cognitive deficiency noted post-livertransplantation might be a result of consequentialmetabolic derangement before liver transplantation.Long-chain polyunsaturated fatty acids, especiallyarachidonic acid (AA) and docosahexaenoic acid(DHA), affect the development of central nerve systemand its absorption is influenced by obstructive jaundice.AIM: To investigate the possible relationship betweenbrain content of AA and DHA with the severity ofobstructive jaundice using bile duct ligation rat model.METHODS: Sprague-Dawley rats were divided into 3groups: Sham (n=5): Rats received sham operation onP17 (17 days after delivery) and sacrificed on P31;BDL2w (n=5): rats received bile duct ligation andsacrificed on P31; BDL4w (n=7): rats received bile ductligation and sacrificed on P45. Liver function test,histo-pathology, and fatty acid composition of the braintissues were analyzed.RESULT: Sham group had significantly loweredtotal/direct bilirubin level (0.6+0.1/0.3+ 0.1 mgdl -1 ) ascompared to BDL2w group (3.8+1.5 /1.6+ 1.0 mgdl -1 )and BDL4w group (4.3+0.6 /3.3+ 0.5 mgdl -1 ); p valueswere 0.04 and 0.008 respectively. Liver fibrosis andinflammatory changes of hepatocytes increased fromSham, BDL2w, to BDL4w groups. Sham group hadsignificantly higher AA and DHA content. Brain contentof AA and DHA correlated negatively to the duration ofbile duct ligation, the total/direct bilirubin level, and thedegree of liver fibrosis.CONCLUSION: Our results demonstrated that reducedAA and DHA content in the brain of rats received bileduct ligation is closely related to both the severity ofliver fibrosis and the impairment of liver function.[Keywords] Arachidonic acid, bile duct ligation,docosahexaenoic acid, obstructive jaundice147

FP22-8DEVELOPMENT OF AUTOANTIBODIES INTHE PEDIATRIC LIVERa TRANSPLANTATIONChing-Yi Chen 1 , Ming-Chih Ho 2 , Jia–Feng Wu 3 ,Yung-Ming Jeng 4 , Rey-Heng Hu 5 , Huey–Ling Chen 6 ,Yen–Hsuan Ni 7 , Mei–Hwei Chang 8 , Po-Huang Lee 9Pediatrics, Children’s Hospital, National Taiwan University 1 , Surgery, NationalTaiwan University Hospital, Taipei, Taiwan 2 , Pediatrics, Children’s Hospital,National Taiwan University, Taipei, Taiwan 3 , Pathology, National TaiwanUniversity Hospital, Taipei, Taiwan 4 , Surgery, National Taiwan UniversityHospital, Taipei, Taiwan 5 , Pediatrics, National Taiwan University ChildrenHospital 6 , Pediatrics, National Taiwan University Children Hospital 7 ,Pediatrics, National Taiwan University Children Hospital 8 , Surgery, NationalTaiwan University Hospital, Taipei, Taiwan 9OBJECTIVE: In recent reports, de novo autoimmunehepatitis is the long-term complication after livertransplantation (LT). These patients did not have autoimmuneliver disease before LT. Autoantibodies are not screenedroutinely after LT and there is no data of the incidence inTaiwan. The aim of this study was to analyze the incidence ofdevelopment of autoantibodies in those children transplantedfor non-autoimmune liver disorders.METHODS: From 1992 to 2008, 94 pediatric livertransplantations for non-autoimmune liver disorders wereperformed at 92 children (39 male and 53 female) in ourinstitution. Pre- and post-operative clinical data werecollected retrospectively for each transplant patient. Serumautoantibodies were analysed by indirectimmunofluorescence during clinic follow-up in 39 subjects(42.4%) after LT. A positive autoantibody was defined astiters >/= 1:80 for antinuclear antibody (ANA), >/= 1:40 foranti-smooth muscle antibody (anti-SM), or >/= 1:20 foranti-liver-kidney-microsomal antibody (LKM) andanti-mitochondrial antibody (anti-mit.). Patient received liverbiopsy while they had abnormal liver function test.RESULTS: Autoantibodies were detectable in 29 (12 male)of 39 (15 male) patients (74.4%). There were ANA-positivein 12 patients, anti-SM-positive in 20 patients, and anti-mit.-positive in one subject. The LKM antibody was negative forall patients. The development of autoantibodies did notassociate with gender, underlying disease, age of livertransplantation, and presence of rejection after livertransplantation. The usage of cyclosporine immediately aftertransplantation is associated with the positivity of ANA(Odd’s ratio, 5.71; p

FP23-2KMUP-1 ATTENUATESISOPROTERENOL-INDUCED CARDAICHYPERTROPHY IN RATS THROUGHNO/CGMP/PKG AND ERK1/2/CALCINEURIN APATHWAYSJong-Hau Hsu, Jiunn-Ren Wu, Zen-Kong Dai, Jwu-LaiYeh and Ing-Jun ChenDepartment of Paediatrics, Kaohsiung Medical University Hospital andGraduate Institute of Pharmacology, College of Medicine, Kaohsiung MedicalUniversity, TaiwanOBJECTIVES: To determine whether KMUP-1, anovel xanthine-based derivative, attenuatesisoproterenol (ISO)-induced cardiac hypertrophy inrats, and if so, whether the antihypertrophic effect ismediated by the nitric oxide pathway.METHODS: In vivo, cardiac hypertrophy was inducedby daily subcutaneous injection of ISO (5mg·kg -1·day -1 ) for 10 days in Wistar rats. In thetreatment group, KMUP-1 was administered one hourbefore ISO. After 10 days, effects of KMUP-1 onsurvival, cardiac hypertrophy and fibrosis, theNO/cGMP/PKG and hypertrophy signalling pathways(calcineurin A and ERK1/2) were examined. Toinvestigate the role of nitric oxide synthase (NOS) inthe effects of KMUP-1, a NOS inhibitor,N-omega-nitro-L-arginine (L-NNA) was administeredalong with KMUP-1. In vitro, antihypertrophic effectsof KMUP-1 were studied in ISO-induced hypertrophicneonatal rat cardiomyocytes.MAIN RESULTS: In vivo, KMUP-1 pretreatmentattenuated the cardiac hypertrophy and fibrosis, andimproved the survival of ISO-treated rats. Plasma NOx(nitrite and nitrate) and cardiac eNOS, cGMP and PKGwere all increased by KMUP-1. The activation ofhypertrophic signalling by calcineurin A and ERK1/2in ISO-treated rats were also attenuated by KMUP-1.All these effects of KMUP-1 were blunted bysimultaneous administration of L-NNA. In vitro,similarly, KMUP-1 attenuated hypertrophic responsesand signalling induced by ISO in neonatal ratcardiomyocytes.CONCLUSION: KMUP-1 attenuates cardiachypertrophy in rats with ISO-induced cardiachypertrophy. These effects are mediated, at least inpart, by NOS activation. This novel agent targeting theNO/cGMP pathway has a potential role in theprevention of cardiac hypertrophy.FP23-3SPECTRUM OF INFECTIVE ENDOCARDITIS INCHILDREN POPULATION: PAST AND PRESENT1 Hok-Keong Chang, 2, Wen Pin Hung, Wen-Lan Yen,Jieh-Neng Wang,Jing-Ming WuDepartment of Pediatrics, National Cheng Kung University Hospital, Tainan1 Department of Pediatrics, Sin-Lau Hospital, Madou Branch,Tainan, Taiwan2 Department of Pediatrics, Kuo General Hospital, Tainan, TaiwanBACKGROUND: Infective endocarditis (IE) is notuncommon in children population. Streptococcus viridans wasthe leading pathogen in the past. Characteristic of IE may bechanged due to improve survival in congenital heart disease,more frequent cardiac surgery, expansion of neonatal care inprematurity patients, and more frequent using indwellingcatheter such as central venous catheter in intensive care unitPATIENT AND METHODS: From August 1998 to October2009, we retrospectively reviewed the patients with diagnosedof IE with or without congenital heart disease. The data basewas based on ICD number of IE and was search in NationalCheng Kung University Hospital Medical Record Department.Clinical data were collected which included age, gender,clinical manifestation, laboratory data, pathogen of IE, tool ofechocardiography, and management. The definition of IE wasdiagnosed by Duke’s criteria. The data then subdivided to twogroups by comparison the year of 1988-1999 and 2000-2009.The data was presented with histogram and pie chart.Continuous variables are summarized by using mean andstandard deviation.RESULTS: Total 48 cases were identified in this cross sectionstudy. 2 cases were recurrent IE with duration of 2 and 5 yearslater. By comparison of this two decade, the incidence of IEremains the same. Streptococcus viridans and Staphylococcusaureus are the most common pathogens that caused IE. Thelatter was increased from 20.8% to37.5 % in recent decade. Inpredisposing factors, decreasing trend in simple congenitalheart disease from 52% to 39%. However in complex heartdisease, the incidence remained the same with 24%. Dentalprocedure induced IE were slightly decreased with incidence of28% to 17.4%. Embolic phenomenon was accounts for 40% ofthis study. There was 33% patients need surgical intervention.The most common reasons for surgical intervention wereembolic episodes occurred and valvular dysfunction.CONCLUSION: The characteristic of IE is changing in therecent era by the implementation of neonatal care, antibioticprophylaxis and surgical management. Staphylococcus aureushas become the most common pathogen in the future. Surgicalmanagement of IE may be needed if treatment failure.[Keywords] Infective endocarditis, children[Keywords] KMUP-1, cardiac hypertrophy, isoproterenol, nitricoxide, calcineurin A149

FP23-4BREAKTHROUGH VARICELLA INFECTIONAND VACCINE EFFICACY IN TAIWANWen-Chan Huang, MD a , Li-Min Huang, MD, PHD a ;I-Shou Chang, MD b ; Fang-Yu Tsai, MS b , Chun-Yi Lu,MD, PhD a , Pei-Lan Shao, MD a , Luan-Yin Chang, MD,PHD aDepartment of Pediatrics, National Taiwan University Hospital, College ofMedicine, National Taiwan University, Taiwan a and Department of BiomedicalInformatics, National Health Research Institute, Miaoli, Taiwan bOBJECTIVE: To decrease the disease burden caused byvaricella infection, free one-dose varicella vaccination forchildren at 1 year of age started in Taipei City since 1998 andin Taichung City/County since 1999. The free varicellavaccination became a national-wide program since 2004. Tounderstand breakthrough infection rate and vaccine efficacyafter varicella vaccination, we thus did this epidemiologicalstudy in Taiwan.METHODS: From 2000 through 2007, 1,057,345 personsreceived varicella vaccines in Taiwan, registered in NationalImmunization Information System. Mean age of therecipients was 1.63 (±1.09) years of age. We analyzed thedatabase of Taiwan’s National Health Insurance claims toinvestigate the varicella infection among the vaccinees andthe unvaccinated, and compared to the incidence of varicellainfection between the two groups to evaluate the vaccineefficacy.RESULTS: There were 2.14% (22,640/1,057,345) vaccineeshad varicella breakthrough infection and 0.02%(170/1,057,345) required hospitalization between 2000 and2007. Annual breakthrough infection rate ranged from 0.1%to 2%. The mean age was 3.93 (±2.08) years of age and themean interval between vaccination and the breakthroughinfection was 841.4 (±682.1) days. Breakthrough infectionrate among males and females were 5.1% and 4.4%,respectively (p

FP23-6IMMUNOGENICITY AND SAFETY OF AMONOVALENT VACCINE FOR THE 2009PANDEMIC INFLUENZA VIRUS A (H1N1) INCHILDREN AND ADOLESCENTSChun-Yi Lu, MD, PhD; Pei-Lan Shao, MD; Luan-YinChang, MD, PhD; Yhu-Chering Huang, MD, PhD;Cheng-Hsun Chiu, MD, PhD; Tzou-Yien Lin, MD; Li-MinHuang, MD, PhDDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan;Department of Pediatrics, Chang-Gung Memorial Hospital, Taoyuan, TaiwanBACKGROUND: The 2009 pandemic influenza A(H1N1) has caused significant morbidity and mortalityaround the world. There is an urgent need of vaccinesfor the virus. Safety and immunogenicity studies of2009 pandemic influenza A (H1N1) virus in childrenand adolescents are lacking.METHODS: In this prospective, open-label study, 2doses of a monovalent, unadjuvanted, inactivated,split-virus 2009 pandemic influenza virus A (H1N1)vaccine were administered to healthy children andadolescents aged 1 to 17 years. Adverse reactions wereassessed, and hemagglutination inhibition antibodytiters were determined.RESULTS: A total of 180 children and adolescentswere enrolled. Antibody responses to a single dose ofthe study vaccine were different in different agegroups. Three weeks after the first dose of vaccination,36.2% (95% CI, 24.0%-49.9%) of children aged 1-2years, 52.5% (39.3%-65.4%) of children aged 3-5years, 56.7% (37.4%-74.5%) of children aged 6-9years, and 90.3% (74.2%-98.0%) of adolescents aged10-17 years generated protective antibodies. A secondvaccination given 3 weeks apart induced protectiveantibodies in 89.4% of all age groups. No severeadverse effect was found 6 weeks after vaccination.CONCLUSION: The Adimmune 2009 pandemicinfluenza A (H1N1) vaccine is well-tolerated inchildren. A single dose of the study vaccine can elicit aprotective immune response in adolescents aged 10to17 years 3 weeks after vaccination. Children aged 1to 9 years need two doses of the study vaccine toensure a seroconversion. (ClinicalTrials Identifier:NCT01007201)FP23-7CLINICAL FEATURES AND RISK FACTORS OFSEVERE NOVEL H1N1 INFECTIONS INTAIWANESE CHILDRENLuan-Yin Chang 1 , Wei-Hua Chen 1 , Li-Min Huang 1 ,Chun-Yi Lu 1 , Pei-Lan Shao 1 , Ping-Ing Lee 1 , Chuan-LiangKao 2 , Ming-Yi Chung 21 Division of Pediatric Infectious Diseases, Department of Pediatrics, NationalTaiwan University Hospital, Taipei, Taiwan; 2 Department of LaboratoryMedicine , National Taiwan University Hospital ,Taipei, TaiwanOBJECTIVE: Data on hospitalized novel H1N1infected children are limited and urgently in demand, sowe did a clinical study to find the clinical features andrisk factors associated with children’s severe novelH1N1 infections in Taiwan.METHODS: From July 24, 2009 to Dec 4, 2009, 61hospitalized children infected with 2009 novel H1N1were collected. Their demographics, underlying medicalconditions, clinical data, receipt of antiviral therapy,need for intensive care and outcome were analyzed tofind clinical features and risk factors of severeinfections.RESULTS: Of the 61 inpatients, the male to femaleratio was 41 to 20 and the most common age group isbetween 6 and 12 years old (36%). Twenty four (39%) ofinfected children had at least one underlying diseaseincluding asthma, immunosuppression; congenital heartdiseases and neurological diseases. Almost all (98%) thepatients had fever, 53 (87%) patients receivedoseltamivir treatment and 51% of them receivedoseltamivir within 48 hours. Fourteen (23%) neededintensive care and 3 died. Body mass index (BMI)>=25,dyspnea, C-reactive protein (CRP)>3 mg/dL, havingpleural effusion and delayed antiviral therapy weresignificantly associated with the need of intensive careand/or death.CONCLUSIONS: BMI>=25, dyspnea, CRP >3 mg/dL,having pleural effusion and delayed antiviral therapywere significantly associated with severe novel H1N1infections and cautious monitor of these parameters andearly treatment may improve the outcome.[Keywords] novel H1N1, children, risk factors, outcom[Keywords] influenza, vaccine, pandemic H1N1 vaccine, children151

FP24-1BLOCKAGE OF PLACENTA GROWTHFACTOR ATTENUATES ACID-INDUCEDACUTE LUNG INJURY IN MICEYi-Li Hung, MD, 1 Wu-Shiun Hsieh, MD, 2 Hung-ChiehChou, MD, 2 Chien-Yi Chen, MD, 2 and Po-Nien Tsao, MD,PhD 21 Department of Pediatrics, Cathay General Hospital, 2 Department ofPediatrics, National Taiwan University Hospital and National TaiwanUniversity College of Medicine, Taipei, TaiwanBACKGROUND: Acute respiratory distresssyndrome (ARDS) is an acute lung injury with highmortality rate. The mechanism is still unclear. Placentagrowth factor (PlGF) has been found to be associatedwith inflammatory process. However, its role inpulmonary ARDS is still unknown. Here, weinvestigated the role of PlGF in acid-induced acutelung injury mouse model.METHOD: We used 3 different mutant mice: PlGFtransgenic (TG), PlGF knockout (KO) and wild type(WT) control mice. Intratracheal injection with HCL(0.1N; 2ml/kg) followed by a bolus of air (30 mL/kg)to induce ARDS. Animals received saline instead ofHCL in the same manner and served as the controlgroup. Mice were euthanized 4 hours or 24 hours afteracid injection. Bronchoalveolar lavage (BAL) wascollected to analyze the cell counts and total proteinamount. Blood was aspirated from the right ventriclefor venous gas analysis and the lungs were removed toassess the extra-vascular lung water, the lung injuryscores and the histopathological changes.RESULTS: Acid injection (4 hours after acid) inducedsignificant hypercapnea and respiratory acidosis in allmice compared to saline group. PlGF TG micedeveloped most severe respiratory failure includinghighest pCO2, total PMN count of BAL, most excessextra-vascular lung water and lung injury score amongPlGF TG, WT and KO mice. In contrast, PlGF KOmice had lowest pCOP2, fewest extravascular lungwater and lowest lung injury score among them. The 24hours mortality rate of acid challenge was also highestin PlGF TG mice followed by WT and KO mice(69.2%, 31%, 7.1%, respectively).CONCLUSION: Our data suggest that PlGF is amediator of acute lung injury induced by acid injection.Inhibition of PlGF signaling pathway may have aprotective effect against acid induced ARDS.[Keywords] Placenta growth factor; acute lung injuryFP24-2PREDICTING SIGNIFICANTHYPERBILIRUBINEMIA IN TERM ANDNEAR-TERM NEWBORNS WITH EXCLUSIVEBREASTFEEDINGHsin-Chung Huang 1 ,Yu Hsun Chang 3 ,Rui-JaneChang 4 ,Mei-Huei Chen 5 , Chien-Yi Chen 6 , Hung-ChiehChou 7 ,Wu-Shiun Hsieh 8 , Po-Nien Tsao 9Pediatrics, National Taiwan University Hospital 1 , Genomics Research Center,Academia Sinica 2 , Department of Pediatrics, Buddhist Tzu Chi General Hospital,Hualien 3 , Division of Neonatology, Department of Pediatrics, Buddhist Tzu ChiGeneral Hospital, Hualien 4 , Department of Pediatrics, Cardinal Tien Hospital,Yung Ho Branch 5 , Division of Neonatology, Department of Pediatrics, NationalTaiwan University Hospital 6 , Division of Neonatology, Department of Pediatrics,National Taiwan University Hospital 7 , Pediatrics, National Taiwan UniversityHospital 8 , Pediatrics, National Taiwan University Hospital, Taiwan 9OBJECTIVE: Neonatal hyperbilirubinemia is the leading cause ofreadmission of newborns in their first week of life. This study wasundertaken by using the clinical data from the first 3 days of life toidentify the high risk newborns who will subsequently developsignificant hyperbilirubinemia within their first 10 days of life.METHODS: We retrospectively collected exclusively breast-feedinghealthy term and near-term newborns who were born in our nurserybetween 2002 May to 2005 Jun. Those neonates who had evidence ofhemolysis, G6PD deficiency, early onset hyperbilirubinemia,cephalohematoma, congenital infection, perinatal asphyxia and majororgan anomaly were excluded. Serum bilirubin was checked at 3 daysold or if icteric skin appearance was identified. Bilirubin level≧15mg/dL during 4 th to 10 th days of life was defined as significanthyperbilirubinemia. A prediction model to predict subsequenthyperbilirubinemia after 3 days old was developed. This risk predictionmodel was externally validated in another group of newborns whowere born between 2009 Jan. to 2009 Apr. by the same criteria to testthe discrimination capability of our prediction model.RESULTS: Totally, 1979 neonates were collected during the firstperiod. According to our exclusion criteria, 1208 cases were excluded.Finally, 771 exclusive breastfeeding newborns were enrolled and23.6% (182/771) cases developed significant hyperbilirubinemiaduring 4 th to 10 th day of life. In the univariate logistic regressionanalysis, gestational age, maximal body weight loss ratio and peakbilirubin level during first 72 hours of life were significantly associatedwith subsequent hyperbilirubinemia. A prediction model incorporatinggestational age, maximal weight loss ratio and peak bilirubin levelduring first 72 hours of life was derived with the area under ROC curve(AUROC) of 0.788 and the multivariate-adjusted odds ratio (95%confidence interval) of 0.78 (0.66-0.91), 1.22 (1.11-1.35), and 1.58(1.44-1.74), respectively. Model validation in the separate population(N=209) showed similar discrimination capability (AUROC=0.8340).By using the predicted probability of 0.177 as the cut-off point, thesensitivity was 90% and specificity was 66.0%.CONCLUSION: Gestational age, maximal body weight loss ratio (%)and peak microbilirubin level during the first 3 days of life havehighest predictive value of subsequent significant hyperbilirubinemia.Here, we provide a good model to predict the risk of subsequentsignificant hyperbilirubinemia. We hope that individualized follow-upprogram and management plan can be made by our predicted risk at 3days old to decrease the incidence of significant or severehyperbilirubinemia.[Keywords] Neonates, hyperbilirubinemia, risk factor, predictive model152

FP24-3HEALTH CARE COST OF VERY LOW BIRTHWEIGHT INFANTS FROM BIRTH TOPRE-SCHOOL AGE UNDER NATIONALHEALTH INSURANCE PROGRAMYung-Chieh Lin 1 , Yu-Tung Huang 2 , Yuh-Jyh Lin 3 ,Chyi-Her Lin 4Pediatrics, National Cheng Kung University Hospital 1 , Department of PublicHealth, National Cheng Kung University 2 , Pediatrics, National Cheng KungUniversity Hospital 3 , Pediatrics, National Cheng Kung hospital, Taiwan 4OBJECTIVES: This study was to examine the health carecost of very low birth-weight (VLBW) infants comparingwith normal birth-weight (NBW) infants from birth topre-school age.METHODS: We conducted a population based, retrospectivecohort nested case-control approach study using the sampledNational Health Insurance Research database (LHID2005) ofTaiwan which included the histories of admissions, length ofstay (LOS), out-patient department (OPD) and emergencyroom (ER) visiting. The sampled size was 400,000individuals. For VLBW group, we identified infants bornwith ICD-9 or ICD-10 for birth weight

FP24-5EFFICACY OF DIFFERENT PROBIOTICSSUPPLEMENT IN PRETERM VERY LOWBIRTH WEIGHT INFANTS TO PREVENTNECROTIZING ENTEROCOLITIS OR DEATH:A META-ANALYSISHisao-Yu Chiu, Hsin-Yang Hsieh, Hsiang-Yu Lin,Ming-Hsia Lin, Bai-Horng Su, Hung-Chih LinDivision of Neonatology, Department of Pediatrics, China Medical UniversityHospital, Taichung, TaiwanOBJECTIVES: To compare the efficacy of differentprobiotics for prevention of necrotizing enterocolitis(NEC) or mortality rate in preterm very low birth weight(PVLBW) infants.METHODS: Literature searches were made ofMEDLINE, EMBASE, Cochrane Library ControlledTrials Register, and abstracts of annual meetings of theSociety for Pediatric Research and the European Societyof Pediatric Research. Only randomized-controlled trialsof PVLBW infants and the outcome measurementincluded NEC or death were enrolled. These trials weresubsided into 3 groups according to the treatment ofprobiotics, (mixture flora, Lactobacillus alone, andBifidobacterium alone). Meta-analysis was performedusing Comprehensive Meta-analysis Version 2.Heterogeneity was estimated by the Q-value, P-value andI-squared statistic. A fixed model was used.RESULTS: Eleven eligible randomizing trials of 2246PVLBW infants were enrolled. The incidence of NEC(risk ratio 0.333, p < 0.0001) and mortality rate (risk ratio0.342, p

FP24-7NEURODEVELOPMENTAL OUTCOME OFEXTREMELY LOW BIRTH WEIGHT INFANTSWITH LEUKEMOID REACTION:A CASE-CONTROL STUDYMing-Luen Tsai, Ming-Chou Chiang, Reyin Lien,Ren-Huei Fu, Jen-Fu Hsu, Shih-Ming Chu, Chang-YoYang, Peng-Hong YangDivision of Neonatology, Department of Pediatrics, Chang Gung Children’sHospital, Chang Gung University College of Medicine, Taoyuan, TaiwanOBJECTIVE: Leukemoid reaction (LR) in extremely lowbirth weight (ELBW) infants is not common. The clinicalsignificance and neurodevelopmental outcome of LR inELBW infants is not well understood.METHODS: This is a retrospective case-control study. LRwas defined as an absolute neutrophil count (ANC) of>30x10 3 /mm 3 . Inclusion criteria included all ELBW infantsadmitted to the NICU of Chang Gung Children’s Hospitalbetween January, 2004 and December, 2007 who had LR. Foreach LR case, we matched with two infants with comparablegestational age and birth body weight (1:2). Medical recordswere reviewed for maternal condition and clinicalcharacteristics of infants. Bayley Scale of InfantDevelopment, Second Edition, was performed at 6, 12, 18and 24 months of corrected age to evaluate theirneurodevelopmental outcome.RESULTS: Twenty-two infants were met inclusion criteria.Incidence of maternal chorioamnionitis was significantlyhigher in the LR group, compared to the control group (41%vs. 9%, p=0.002). There was no difference in other maternalconditions and the use of antenatal steroid between these 2groups. Infants between 2 groups had no different in gender,gestational age, birth body weight, Apgar scores, pulmonarycondition, respiratory distress syndrome, sepsis,periventricular leukomalacia (PVL), patent ductus arteriosus,retinopathy of prematurity, mortality and length ofhospitalization. Infants with LR had higher incidence ofnecrotizing enterocolitis (NEC), severe bronchopulmonarydysplasia (BPD), and severe intraventricular hemorrhage(IVH). The scores of Mental Development Index (MDI) inLR and control groups were 86±16 vs. 95±8 at 6 months,82±19 vs. 92±9 at 12 months, 86±22 vs. 90±3 at 18 monthsand 76±27 vs. 91±13 at 24 months, respectively. The scoresof Psychomotor Development Index (PDI) in LR and controlgroups were 79±14 vs. 86±13 at 6 months, 71±16 vs. 81±12at 12 months, 85±20 vs. 99±0 at 18 months and 84±22 vs.95±14 at 24 months, respectively.CONCLUSIONS: ELBW infants with LR is associatedmaternal chorioamnionitis, but not with neonatal sepsis.Inflammatory cascade is speculated to account for thephenomenon and subsequent IVH, NEC and BPD. There isno difference in scores of MDI and PDI before 2 years;however, long-term follow up is needed.FP24-8WEANING FROM NCPAP IN VLBW INFANTS: APROSPECTIVE PILOT RANDOMIZEDCONTROLLED TRIALChang-Yo Yang, Reyin Lien, Mei-Ching Yang*,Tzu-Hui Lei , Peng-Hong Yang, Shih-Ming ChuDivision of Neonatology, Depts. of Pediatrics and *Respiratory Care, ChangGung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan,TaiwanOBJECTIVES: The aim was to compare the practicality andeffectiveness of three weaning protocols we designed to facilitateweaning VLBW preterm infants from nasal positive pressure support.With this study, we also aimed to standardize the weaning practice.MATERIALS AND METHODS: This is a prospective randomizedcontrolled study enrolling VLBW preterm infants (BW≤1500 gm andGA1250 gm. Patients were randomized to one ofthe three weaning protocols: A) CPAP Gr. Continue CPAP 5cmH 2 O foranother 5 days, then intermittently off to room air, no pressure support.B) O 2 flow Gr. Start intermittently off CPAP to O 2 flow 0.2 to 0.1L/min by nasal cannula. C) High flow air Gr. Start intermittently offCPAP to air flow 1.5 L/min by nasal cannula. Duration of CPAP offwas increased daily by the same fashion in 3 groups. The weaningprocess was considered successful if the patient remained stable offCPAP for 5 days. The following data were analyzed: patients’demographic data, length of weaning duration; body weight and PMAof successful weaning; causes of failure; risk of complications (ROPand BPD) and length of hospital stay.RESULTS: There were a total of 181 patients enrolled in the study, 55in Gr.A, 63 in Gr. B and 63 in Gr. C. The birth weight and GA weresimilar in three groups. The mean body weight and PMA of successfulweaning for the 3 groups were 1941±497 g and 35.4±2.0 wks,1808±416 g and 34.9±2.0 wks; and 1981±614 g and 35.6±2.4 wks,respectively. While body weight was still less than 1500 gms, about 1/3of the infants were able to come off nCPAP in Grs. A and C, whereas50% of the infants were successfully weaned in Gr. B. The time(duration) needed to wean off pressure support in Gr. A, B and C was16.0±10.0 days (mean), 11.6±6.4 days, and 15.0±8.9 days, (p=.033).However, the overall incidence of BPD and ROP incidence wassignificantly higher in patients weaning by O 2 flow (P =.048).CONCLUSION: Although using O 2 flow took a shorter duration towean off nCPAP, the length of hospital stay was no different in all 3groups. Essential factor to guarantee successful weaning is clinicalstability and not body weight or PMA. Weaning by O 2 flow seems tohave detrimental effects in the development of BPD and ROP, whichcould be related to oxygen toxicity. Therefore, we suggest weaningshould be started early if the infant is clinically stable under nasalCPAP of 5–7 cmH 2 O and FiO 2 ≦25%. Unless the infant has BPD andis O 2 dependent, weaning should consider using air flow or justsplinting with no support at all.[Keywords] nCPAP; weaning protocol; VLBW infants[Keywords] Neurodevelopmental Outcome; Extremely Low BirthWeight Infants ; Leukemoid Reaction155

FP25-1ALLERGIC SENSITIZATION IN THEWHEEZE-EVER FIRST GRADE SCHOOLCHILDREN IN TAIPEIChing-Hsiang Chuang*, Wei-Fong Wu*, Kong-SangWan*, Shu-Chen Chao*,Winnie Yang**Department of Pediatrics, Division of Serology and Immunology, Taipei CityHospital, Ren-Ai Branch*, Yang-Ming Branch** (Taiwan)OBJECTIVE: There is increasing evidence that the prevalenceof asthma and other allergic disease has been increasing inchildren during the past 4 decades, especially in Westerncountries. Several epidemiological studies also revealed that thesimilar trend was observed in Taipei, Taiwan. It is welldocumented that allergy plays a significant role in thepathogenesis of asthma in children. The objective of this studywas to investigate the prevalence and distribution of allergicsensitization in the wheeze-ever first grade school children inTaipei.METHODS: This study had a prospective cross-sectionaldesign. The survey was conducted between March 2009 andDecember 2009. A simplified form of ISAAC (InternationalStudy of Asthma and Allergies in Childhood) questionnaire wassent to all the first grade school children in Taipei. Of all therespondents (n=22815), those children whose parent answeredyes to the question “Has your child ever had wheezing orwhistling in the chest at any time in the past?” and agreed to jointhe study were recruited. A blood sample was taken from eachincluded child for specific IgE antibody determination(Phadiatop) using a Pharmacia CAP System. The sera werestored in aliquots at -70℃. Thawed sample were tested in largebatches. If a positive result was found, an additional 5 group mix(animal epidermal, house dust, mold, seafood, children’s food)and further 12 specific IgE tests were performed.RESULTS: The prevalence of wheeze-ever was 20.74%(4731/22815). A total of 2483 children were included in theserology study. The Phadiatop test was positive in 76.36%(78.69% in boys, 72.70% in girls) of these children. The positiverates in the 5 group mix allergens were: house dust 95.6%,animal epidermals 59.9%, children’s food 40.7%, sea food24.6%, mold 5%. Among the specific IgE tests,Dermatophagoides pteronyssinus was the commonest allergen(94.4%), followed by Dermatophagoides farinae (92.7%),Blomia tropicalis (84.2%), shrimp (24.2%), German cockroach(20.6%), egg white (18.2%), milk (17.9%), dog dander (14.3%),crab (11.9%), cat dander (8.8%), codfish (2.3%), A. alternate(2.3%).CONCLUSION: The use of specific IgE antibodydeterminations improves the clinical management of patientswith allergy related symptoms in primary care. In this study,allergy sensitization rate was rather high in the wheeze-ever firstgrade school children in Taipei. House dust mite such as D.pteronyssinus, D. farinae, B. tropicalis and shrimp, Germancockroach were the major allergens. This data allowed advice tobe given on specific allergen avoidance during environmentalcontrol maneuver.FP25-2THE CORRELATION OF TOURETTE’SSYNDROME AND ALLERGIC RHINITIS: ANATIONWIDE POPULATION BASEDCASE-CONTROL STUDYYu-Tzu Chang 1 , I-Ching Chou 1,3 *, Zheng-Nan Chin 1 ,Huang-Tsung Kuo 2 and Chang-Hai Tsai 1,41 Department of Pediatric Neurology, Children’s Medical Center, China MedicalUniversity Hospital, Taichung, Taiwan; 2 Division of Development and BehaviorPediatrics, China Medical University Hospital, Taichung, Taiwan; 3 GraduateInstitute of Integrated Medicine, College of Chinese Medicine, China MedicalUniversity, Taichung, Taiwan; 4 Department of Healthcare Administration, AsiaUniversity, Taichung, TaiwanOBJECTIVES: Tourette’s syndrome has a multifactorialetiology. The linkage between allergy and increasedactivation of immune responses in Tourette’s syndrome hasbeen reported. We perform this case-control study toevaluation the incidence of Tourette’s syndrome in differentage-, sex-, and the correlation between allergic rhinitis andTourette’s syndrome in Taiwan.METHODS: The data used in this case-control study wasfrom the Taiwan National Health Insurance ResearchDatabase. A total of 845 patients with Tourette’s syndromenewly diagnosed in 2003-2007 of age from 2 to 18 yearsand randomly selected 3,380 controls. We used chi-squaretest for descriptive analysis and logical regression analysisto estimate odds ratios (ORs) and 95% confidence intervals(CIs) for observing the association between allergic rhinitisand associated factors.MAIN RESULTS: The overall incidence of Tourette’ssyndrome with age from 2 to 18 years since from 2000 to2007 is 81.0 per 100,000 populations (from 58.7 to 103.2).The incidence of Tourette’s syndrome was higher in male(76%). The multivariate logistic regression analysis showedthat, male had higher risk of Tourette’s syndrome thanfemale (OR=2.76, 95% CI=2.30-3.32). The highest risk wasin age group of 6-9 years compared with age group of 15-18years (OR=10.6, 95% CI=6.93-15.9). Study subjects withallergic rhinitis had significant higher risk to had Tourette’ssyndrome (OR=2.55, 95% CI=2.13-3.05, P< 0.0001).CONCLUSION: As compared with control group,allergic rhinitis patients demonstrated a 2.55-fold increaserisk of developing Tourette’s syndrome. This findingsuggested that there was significant correlation betweenallergic disease and Tourette’s syndrome. Further study forthe mechanism of neuroimmunology of Tourette’ssyndrome may be needed.[Keywords] Tourette's syndrome, allergic rhinitis, Immune, Incidence156

FP25-3MISDIAGNOSED ACUTE APPENDICITIS INCHILDRENYi-Jung Chang 1 , Dah-Chin Yan 2 , Shao-Hsuan Hsia 3 ,Man-Shan Kong 4 , Hsun-Chin Chao 5 , Ming-Wei Lai 6 ,Chang-Teng Wu 7Pediatrics, Chang Gung Memorial Hospital,Taipei 1,2,3,7 , Division of Pediatric4, 5, 6Gastroenterology, Chang Gung Children's Hospital, TaiwanBACKGROUND: To identify clinical features thatdistinguish children with appendicitis who visit theemergency department twice or more from thosediagnosed on the first visit to the emergencydepartment.METHODS: A retrospective review of all childrenwith appendicitis diagnosed in the emergencydepartment between January and December 2004.Records were reviewed for all patients on their initialpresentation to the emergency department. Clinicalfeatures were compared for those children who weremisdiagnosed and for those who were diagnosedcorrectly.RESULTS: One hundred seventy-three cases wereincluded (mean age, 10.4 years). Twenty-six (15%)were seen twice or more in the emergency departmentbefore appendicitis was diagnosed. Misdiagnosedpatients had a relatively shorter duration of symptomsat their initial visit, and most presented late at night.Eighteen misdiagnosed patients (69.2%) initiallyvisited the emergency department within 24 hours ofonset of symptoms. On initial presentation,misdiagnosed patients had a significantly shorterhospital stay, fewer laboratory tests, less right lowerquadrant tenderness, muscle guarding, reboundtenderness, fever, and migrating pain. Patientsdiagnosed late at night had a significantly shorterhospital stay and abdominal ultrasound evaluations. Onfinal presentation, initially misdiagnosed patients had ahigher rate of appendiceal perforation than didcorrectly diagnosed patients.CONCLUSION: Misdiagnosed appendicitis is aproblem in the emergency department. A shorter stay inthe emergency department, fewer laboratory tests, lessdiagnostic imaging, and fewer physical findings maybe responsible for misdiagnosed appendicitis late atnight in the emergency department.FP25-4FEVER (5DAYS) AND REMARKABLE CERVICALLYMPHADENOPATHYS (> 1.5CM) ANDCORONARY ARTERIAL ANEURYSM INKAWASAKI DISEASESYu-Chih Huang 1 , Jeng-Sheng Chang 2* , Hsiao-ChuanLin 3 and Tsu-Fuh Yeh 41 Department of Pediatrics, Tai-An Hospital, Taichung, Taiwan; 2 Division ofPediatric Cardiology, 3 Division of Pediatric Infection, and 4 Division ofNeonatology, Children’s Medical Center, China Medical University & Hospital,Taichung, Taiwan.OBJECTIVES: To search for clinical or laboratoryparameters that can facilitate an early diagnosis of KD onpatients presented with fever and remarkable CLA.METHODS: Medical records of 176 pediatric patientsadmitted to the China Medical University Hospital , Taichung ,Taiwan , during the period of Apr. 1995 through Apr. 2004 bytentative diagnosis of CLA or cervical lymphadenitis or neckmass were identified. Fever was also noted in 142 of them andfever 5 days occurred in 94 patients. At discharge, forty-two(44.7%) fulfilled a diagnosis of KD by meeting more than 5 ofthe 6 criteria, while the other 52 (55.3%) were categorized asnon-KD patients. We further analyze the differences betweenthese 2 groups of patients.MAIN RESULTS: KD patients were younger than non-KD(38+26 v.s. 64+52 months-old, p = 0.006) and showed higherC-reactive protein levels (CRP, 13.5+ 6.4 vs. 5.85+5.5 mg/dl,p< 0.0001). Using the method of area under ROC, a cuttingCRP level of 9.28 was identified to predict KD cases by asensitivity of 76.2% and a specificity of 73.1%. Also, any ofthe other 4 criteria, including skin rash, non-purulentconjunctivitis, lips and oral changes and digital lesions, showedvery much higher occurrence in KD patients than non-KD byodds ratio > 1.5 and p < 0.0001. When any one of these 4criteria was associated with CLA patients, only a CRP level 1.0was required to favor a diagnosis of KD (sensitivity 97.6%,specificity 92.3%). Two months after onset, theechocadiographic studies disclosed coronary arterial aneurysms(CAA) in 12 of these 42 KD patients (28.6%), which washigher than our data base of CAA complication rate in all KDpatients (28/182, 15.3%).CONCLUSION: Remarkable CLA (> 1.5 cm ) and fever 5days are high risk for KD especially when associated with oneof the other diagnostic criteria. (Sensitivity 97.67%, Specificity92.3%) This presentation was associated with high incidence ofcoronary arterial aneurysm on follow-up echocardiogram.[Keywords]Kawasaki diseases, Lymphadenopathy, Coronary ArterialAneurysm[Keywords] appendicitis, child, diagnostic error157

FP25-5PREMATURE THELARCHE IN TAIWANESEGIRLSCheng-Ting Lee 1 , Yi-Chin Tung 2 , Wen-Yu Tsai 3Pediatrics, National Taiwan University Hospital, Taiwan 1,2,3FP25-6METABOLIC SYNDROME IN 7 TH DEGREESCHOOLCHILDREN AT THE PINTUNG CITYWu-Yuan Chen, 1 Chang Daw-Ming, 2 Chuang Lee-Ming, 31 Yuan&Hsin Clinic & Department of Pediatrics, Kaohsiung Medical UniversityHospital, Taiwan; 2 Department of Internal Medicine, Pintung Christian Hospital,Taiwan; 3 Department of Internal Medicine, National Taiwan University, TaiwanOBJECTIVE: To understand the clinical features,hypothalamic-pituitary-ovarian function and naturalcourse of premature thelarche (PT) in Taiwanese girls.METHODS: Ninety-one Taiwanese girls with PT whowas diagnosed younger than six and had been regularlyfollowed up for more than two years were enrolled inthis study. The medical records of these patients werethoroughly reviewed to evaluate their clinical features,laboratory data and natural courses. For comparison,the results of GnRH tests in 25 girls with centralprecocious puberty (CPP) and 10 normal prepubertalgirls were also enrolled for analysis.RESULTS: The age of onset of these patients was1.5±1.6 years and 79% of them developed PT beforethe age of two. The girls with PT had intermediatedegree of hypothalamic-pituitary-ovarian activitybetween prepuberty and puberty with FSHpredominant response in either basal levels or GnRHstimulated hormone levels. 87% of patients hadcomplete regression of breast development during3.8±2.5 years' follow-up. Among them, 22 patients(28%) have experienced one or two episodes ofrecurrence after initial complete regression of breastdevelopment. The cycling intervals between episodesof breast development ranged from 2.5 months to 3.5years (median 3.1 months). Seventeen girls with PT(19%) have progressed to CPP during follow-up andone of them has been treated with GnRH analoguebecause of rapid progression of puberty.CONCLUSIONS: Taiwanese girls with PT more oftendeveloped within the first two years of life. Activationof hypothalamic-pituitary-ovarian axis withpredominant FSH activity during infancy maycontribute to its development. 87% of patients hadcomplete regression of breast development. However,19% have progressed to CPP during follow-up.Therefore, PT is not always a benign self-limitedcondition that clinicians should be cautious aboutpubertal development of these patients.BACKGROUND: The metabolic syndrome (MS) identifiesindividuals at increased risk for cardiovascular disease andtype 2 diabetes. In the past two decades, the prevalence ofoverweight and obesity has increased dramatically in schoolchildren.PURPOSE: The purpose of this study was to estimate theprevalence and distribution of metabolic syndrome and toexplore the risk factors associated with metabolic syndrome ina school-based group of adolescent from Pintung.METHOD: A total of 1478 7 th grade students (748 boys and730 girls; mean age = 13.5±0.4 years) from 2 junior highschools in Pingtung (the southeast part of Taiwan) wereenrolled in this study after informed consent obtained. In thisstudy, obesity and overweight were defined by using the sexandage-specific BMI cutoffs (published by Department ofHealth, R.O.C.). Subjects met at least three of the followingfive characteristics were classified as having metabolicsyndrome: (1) obesity defined by BMI category (2) elevatedblood pressure (systolic≧130 mmHg or diastolic≧85 mmHg);(3) HDL-C < 40 mg/dl; (4) fasting blood glucose ≧ 100 mg/dlor known T2DM; (5) TG ≧ 150 mg/dl.RESULTS: Overall, 32 % of students met at least one and12.3% students met two or more MS category. The overallprevalence of MS was 5.3% and was more common in boys(8.4%) than in girls (2.1%). When classified by BMI category,28.4% of obese, 0.5% of overweight, and 0.2% of normalweight adolescents had the metabolic syndrome. Obesity(17.9%) and low HDL-C (15.9%) was the most common, whilehigh fasting blood glucose level was the least common (2.3%)abnormality. Boys were more common to suffer from any ofthe MS criteria (high BP, 13.4% vs. 3.7%; high fasting glucose,3.7% vs. 1.0%).DISCUSSION: This study showed the prevalence ofadolescent MS at the southeast part of Taiwan is quite the sameas those of the other part of the world. Besides showing obesityas key risk factor for MS, our study also showed the HDL-C tobe the second common abnormality found in our adolescents.Early detection and treatment of these risk factors should helpto focus intervention and improving future cardiovascularhealth.[Keywords] metabolic syndrome, adolescent, obesity, HDL-C, Triglyceride[Keywords] Premature thelarche, central precocious puberty158

FP25-7URINARY MELAMINE LEVELS INASYMPTOMATIC CHILDREN EXPOSED TOMELAMINE ADULTERATION OF POWDEREDINFANT FORMULA—A LONGITUDINALSTUDYCheng-Hsien Tsai 1 , Ching-Hsin Ku 2 , I-Jung Tsai 3 ,Kuen-Yuh Wu 4 , Jun Chen 5 , Chu-Chi Chen 6 , Yong-KweiTsau 7Pediatrics, National Taiwan University Hospital Yunlin Branch 1,2 , Pediatrics,National Taiwan University Hospital 3 , Institutes of Occupational Medicine andIndustrial Hygiene, College of Public Health, National Taiwan University 4 ,Urology, National Taiwan University Hospital Yunlin Branch 5 , Division ofBiostatistics and Bioinformatics, National Health Research Institutes 6 ,Pediatrics, National Taiwan University Hospital, Taiwan 7BACKGROUND: Although epidemiological studies confirmed theassociation between melamine exposure in powdered formula andnephrocalcinosis, lack of valid biomarker and cohort studies werenoted. We defined the urinary melamine creatinine ratio (UMCR) asmeasurement of urinary melamine (mg/L) divided by urinarycreatinine (mol/L) as biochemical marker, and follow-up in thesechildren.METHODS: Inclusion criteria were children who had taken infantformula more than 1 month and birth date after Jan 1, 2005.Exclusion criteria were premature infants, perinatal asphyxia,congenital infection, or maternal addiction. Detailed feeding historywas collected. Children were classified according to taken formulamelamine: Group-1 was defined reported formula melamine levelshigher than 2.5 mg/Kg; Group-2 defined between 0.05-2.5 mg/Kg;Group-3 as undetectable melamine. We checked urine routine andmelamine in all children included but renal echo was performed onlyif any abnormality in urine on the second visit. Urinary melaminewas assayed by HPLC/MS/MS with limit of detection at 0.05 mg/L.All children were contacted 3 months later and rechecked if previousabnormalities. Statistics were performed by Stata 10 with linearregression and ROC analysis. The family consent of this study hasbeen proved by the Institute.RESULTS: 145 children were recruited, including 12(8.3%) inGroup-1, 47(32%) in Group-2, and 86(59%) in Group-3. Accordingfeeding report, 8 brands of formula were tainted with melamine. Thetainted level was reported between 0.123 and 68.2 mg/Kg. Amongthem, 5 brands were packaged in Taiwan. Significantly higher ratioof children in Group-1 was noted in travel history to China, andhigher accumulated melamine intake 819 mg in Group-1 than 9 mgin Group-2 and 0 in Group-3 from formula. The urinary melaminelevels were detectable in 14(10%) of 145 children between 0.065 and0.156 mg/L. Among them, 11(23%) children in Group-2 wassignificantly higher ratio. The UMCR were between 100.4 and 8.6mg/mol. The UMCR higher than 11-20 mg/mol had likelihood ratio2.9- 4.4 to be taken melamine formula. Follow-up later showed thatUMCR were all undetectable in Group-1 and -2 after stopping thetainted formula but 2.3% of children in Group-3 were detectable.Renal echo was performed in 77 (53%) children, including only onechild (0.68%) had nephrolithiasis. This child had the highest UMCR(100.3 mg/mol) in Group-1 and became asymptomatic afterconservative treatment.CONCLUSIONS: For children with melamine-tainted formulaintake, UMCR is the non-invasively diagnostic biomarker asadjuvant. Normal children had 2.3% detectable. Long-term follow-upis necessary.FP25-8COMPARISON OF EPIDEMIC PATTERN FORINFLUENZA/NEO-INFLUENZA ANDENTEROVIRUS INFECTION IN 2008 AND 2009Chia-Wan Tang 1 , Yung-Feng Huang 1 , Ming-Fang Cheng 1 ,Lin Chu-Chuan 1 , Hsieh Kai-Sheng 1Kaohsiung Veterans General Hospital, Kaohsiung, TaiwanOBJECTIVES: To determine interrelation ofinfluenza/neo-influenza and enteroviral epidemic pattern in2008 and 2009.METHODS: A retrospective chart review of patients under 18years with Influenza/neoinfluenza and enteroviral infectionsbetween January 1, 2008 and December 10, 2009 in a tertiarymedical center. Patients diagnosed with either Influenzaantigen quick test with or without positive viral isolations werereviewed in this study. Those patients with herpangina or handfoot mouth diseases were reviewed as well. Seasonaldistributions were the following: spring (February, March andApril); summer (May, June and July); autumn (August,September and October), winter (November and December).MAIN RESULTS: A total of 798 patients were analyzed. Twohundred thirty five cases (21 for year 2008 and 214 for 2009)were Influenza/Neo influenza and a total of 563 (370 for 2008and 193 for 2009) for enterovirus infection. Male to femaleratio was 1.5: 1 for Influenza/neo-influenza and 1.34:1 forenterovirus infection. According to seasonal changes ofenterovirus and influenza/neo-influenza in 2008, our datashowed: spring (45, 2), summer: (225, 1), autumn (69, 9),winter (31, 9) and for the year 2009, spring (43, 9), summer(118, 1), autumn (25,105) and winter (7, 99).CONCLUSION: Compared to 2008 pattern, there was a newepidemic of influenza-neo influenza in 2009, especially afterMay 2009. Epidemic enterovirus disease used to be epidemicin April to June and September to October. However, compareto the epidemic pattern of enterovirus last year, there was adecreased case number of enterovirus infections in 2009.Particularly there were no critical enterovirus cases in 2009.Meanwhile, the case number of enterovirus decreasedsignificantly in autumn associated with concurrent increase ofpan-epidemic of influenza/neo-influenza in the same period.The epidemic survey showed a negative association ofepidemic pattern with two viral syndromes. Viral interferenceor public health isolation measures may play a role for thisparticular phenomenon.[Keywords] influenza, neo-influenza, enterovirus[Keywords] children, melamine, formula, melamine-creatinine ratio,urine159

FP26-1EFFECTS OF INTRATRACHEALINSTILLATION OF BUDESONIDE ANDSURFACTANT IN SURFACTANT-DEPLETEDNEWBORN PIGLETSChia-Feng Yang , Mei-Jy Jeng, Wen-Jue Soong,Yu-Sheng Lee, Pei-Chen Tsao, Ran-Bin TangInstitute of Emergency and Critical Care Medicine, School of Medicine, NationalYang-Ming University; and Department of Pediatrics, Taipei Veterans GeneralHospital, Taipei, TaiwanBACKGROUND: Chronic lung disease (CLD) continues to bemajor complications of premature infants with severerespiratory distress syndrome (RDS) in spite of advancedventilatory care, prenatal corticosteroid, and postnatal surfactanttherapies. The combination use of intratracheal corticosteroidand surfactant may not only recruit the lungs but also alleviatethe pulmonary inflammation in severe RDS.OBJECTIVE: To investigate the pathophysiological effects ofintratracheal instillation of corticosteroid (Budesonide) andexogenous surfactant in an animal model of surfactant-depletedneonatal lungs.METHODS: Eighteen newborn piglets received repeatedpulmonary saline lavages to induce acute lung injuriesmimicking the surfactant-depleted lungs in neonatal RDS, andthen were randomly grouped into control group (no treatment),Surfactant (Surf) group (treated with standard intratracheallyinstilling surfactant 100 mg/kg); and Budesonide plusSurfactant (Bude+Surf) group (treated with intratracheallyinstilling the mixed suspension of Budesonide 0.25 mg/kg andsurfactant 100 mg/kg). Blood samples were examined at 0, 1, 2,3, 4, 6, 8, 16, 24 hr and lasted for 24 hours. The lung tissueswere examined after experiments.MAIN RESULTS: During the 24-hour experiments, we foundbetter oxygenation with higher PaO 2 , alveolar-arterial oxygendifference (A-aDO 2 ), and higher lung compliance in Surf andBude+Surf groups than control group, but there was nosignificantly statistical difference between Surf group andBude+Surf groups. Marked alleviation in pulmonary histologicaldamages and inflammatory cell infiltrations were also observedin both Surf and Bude+Surf groups compared with control group.The lung injury scores demonstrated significant decrease in Surfand Bude+Surf than control groups, and there was also nosignificant difference between Surf and Bude+Surf groups.CONCLUSIONS: Intratracheal instillation of surfactant orsurfactant plus budesonide may improve oxygenation, lungcompliance and pulmonary histological outcome in neonatalsurfactant-depleted lungs in 24 hours. The additional use ofbudesonide didn’t disturb the function of exogenous surfactant,and didn’t further improve the pulmonary outcome insurfactant-depleted lungs. Further studies will be necessary toclarify if there are superior benefits with the use of intratrachealcorticosteroid in addition to exogenous surfactant in RDS.FP26-2PREDICTIVE FACTORS TO IDENTIFYHIGH-RISK CHILDREN WITH COMPLICATEDPARAPNEUMONIC EFFUSIONShen-Dar Chen 1 , Jieh-Neng Wang, Hok-Keong Chang 2 ,Wen-Lan Yen, Ching-Chuan Liu, Jing-Ming WuDepartments of Pediatrics, National Cheng Kung University Hospital, Chia-YiChristian Hospital 1 , Sin Lau Hospital Madou Branch 2 , Tainan, TaiwanOBJECTIVE: Early identify the high risk children withcomplicated parapneumonic effusion (CPE) who needmore invasive procedure is very important. This study isaim to determine the predictive factors for children withCPE.METHODS: From November 1992 to September 2009,children with CPE that received tube thoracostomy plussystemic antibiotics as the first-line therapy in theNational Cheng Kung University Hospital, Tainan,Taiwan were enrolled. Patients who needed rescueprocedure including open thoracostomy, or videoassisted thoracoscopy (VATS) despite adequate first-linetreatment for seven days were classified as the rescuegroup, while the others were classified as theconventional group. We therefore compared the clinicalmanifestations, laboratory characteristics, diseaseseverity by Light’s classification, amount and analysis ofpleural effusion between the conventional group andrescue group.RESULTS: The patient population ranged from 7 to 216months with a mean age of 53.3 months. Total 132patients were included in this study (conventional group:106 patients, rescue group: 26 patients). There were nostatistical differences of age, gender, the duration offever before admission, hemoglobin, c-reactive protein,and pleural effusion characters between these twogroups. While the initial disease severity, white bloodcell count (18534.29±11141.92 /mm 3 vs13066.67±7774.61 /mm 3 ), and platelet count (338.16 ±217.83 K/mm 3 vs 244.15 ± 220.25 K/mm 3 ), werestatistical difference between both groups (p < 0.05).CONCLUSIONS: We found that lower white blood cellcount, and lower platelet count were predictive factors ofchildren with CPE that needed additional procedures.[Keywords] children, parapneumonic effusion, predictive factors[Keywords] Budesonide, Surfactant, RDS160

FP26-3CARDIO-THORACIC INDEX ON CHEST X-RAYIS NOT RELIABLE FOR ASSESSING CARDIACFUNCTION IN PATIENTS WITHENTEROVIRUS 71 INFECTIONChia-Wan Tang 1 , Yung-Feng Huang 1 , Lin Chu-Chuan 1 ,Hsieh Kai-Sheng 1Kaohsiung Veterans General Hospital, Kaohsiung, TaiwanFP26-4ACUTE PATHOPHYSIOLOGICAL RESPONSESIN THE NORMAL LUNGS OF NEWBORNPIGLETS EXPOSED TO PURE OXCYGENPei-Wei Wang, 1,3 Mei-Jy Jeng, 1,2,4 Li-Jung Fang, 3 Wen-JueSoong 1,2,41 Institute of Emergency and Critical Care Medicine and 2 Department ofPediatrics, School of Medicine, National Yang-Ming University; 3 Department ofPediatrics, Taipei City Hospital, Women and Children’s Campus; 4 Departmentof Pediatrics, Taipei Veterans General Hospital, Taipei, TaiwanOBJECTIVES: Cardiopulmonary compromise is themost ominous complication of EV71 infection.Traditionally, we often just use chest x-ray to monitorthe progression of EV71 infection. Usuallycardiomegaly is a pre-requisite for considering cardiacdysfunction. The purpose of this study is therefore toevaluate and compare the measurement ofcardiothoracic (C-T) ratio on plain chest-x-ray andportable echocardiography for assessing cardiacfunction.METHODS: A retrospective review of chest x-ray andechocardiographic findings in patients admitted toPICU due to severe enterovirus 71 infections and acomparison with normal children. Patients with severeenterovirus 71 infection were categorized in: thosestaged 3A according to CDC staging (group I) andstage 3B (group II). Normal children were the groupIII. Cardio-thoracic index were measured from chestradiography at admission and cardiac function wasassessed by echocardiography.MAIN RESULTS: A total of 29 patients wereenrolled. Mean age: 3.62 years old and there were 17males and 12 females. Group I consists of 7 patients,groups II, 10 patients and group III, 12 patients. Themean of cardio thoracic index between Group I, II andIII were 47.4%, 46.6% and 45 %. Meanwhile thecardiac fractional shortening among these groups were48.1%, 24.6% and 52.7 % respectively. Although asignificant difference of cardiac function between thesethree groups (p

FP26-5THE CLINICAL IMPLICATIONS OF LOWERAIRWAY ANOMALIES IN PATIENTS WITHCONGENITAL HEART DISEASE AND CATCH22 SYNDROMEChing-Chia Wang 1 , Shyh-Jye Chen 2 , En-Ting Wu 3 ,Chun-An Chen 4 , Shuenn-Nan Chiu 5 , Ming-Tai Lin 6 ,Frank Lu 7 , MEI-HWAN WU 8 , Jou-Kou Wang 9Pediatrics, National Taiwan University Hospital 1 , Dept. of Radiology, Hospital& College of Medicine, National Taiwan University 2 , Pediatrics, TaiwanUniversity Hospital 3 , Department of Pediatrics, National Taiwan UniversityHospital 4, 5,6, 7,9 , Pediatric Cardiology National Taiwan University Hospital,TaiwanAIMS: To define the lower airway anomalies and the clinicalimplications in congenital heart disease with CATCH 22syndrome.METHODS: Data were retrieved from a retrospective chartreview of the patients who had a definitive diagnosis ofCATCH 22 syndrome by fluorescence in situ hybridizationbetween 1995 and 2007. All patients had congenital heartdisease and underwent computed tomography. Seven patientsunderwent flexible bronchoscopy.RESULTS: Eighteen patients with a total follow-up of 152patient-years (median: 120 months) were enrolled.Characteristic dysmorphic facial features were noted in 8patients (n=8, 44%). Twelve patients (n=12, 67%) had mildto moderate trachea or bronchial stenosis. Five patients (n=5,28%) had tracheomalacia or bronchomalacia. Three of themreceived tracheoplasty. All had associated cardiac anomalies.The spectrum of cardiac anomalies included tetralogy offallot (TOF) (n=16, 88%), truncus arteriosus (n=1, 6%), leftventricular outflow tract obstruction (LVOTO) (n=1, 6%).Eighteen patients received the first major surgery with amedian hospital stays of 48 days (P=0.013) and the time ofventilator usage was16 days (p=0.024). The computedtomography image revealed that the relative length of thetrachea (representing by the length of trachea parallel to thespine) was set by a line through the carina on lung window(level=-600; width=2000) that was perpendicular to the curveof the thoracic spine. The difference of mean level betweenthe control group and the study group is 2.28 ±1.78(P

FP26-7CYTOMEGALOVIRUS INFECTIONASSOCIATED WITH PROLONGED ACQUIREDNEUTROPENIA IN CHILDREN ANDPOTENTIAL INVOLVEMENT OFMESENCHYMAL STROMAL CELLSJiunn-Ming Sheen 1 , Ho-Chang Kuo 2 , Hong-RenYu 3 , Eng-Yen Huang 4 , Kuender D. Yang 5Pediatrics, Chang-Gung Memorial Hospital 1 , Division of Pediatric Allergy andImmunology; Department of Pediatrics, Chang Gung MemorialHospital-Kaohsiung Medical Center; Chang Gung University, Kaohsiung,Taiwan 2 , Department of Pediatrics, Chang Gung MemorialHospital-Kaoshiung Medical Center 3 , Radiation Oncology, Chang-GungMemorial Hospital 4 , TBC, Chang Gung Memorial Hospital at Kaohsiung; andChang Gung University, Taiwan 5OBJECTIVE: Neutropenia is an important cause ofmorbidity and mortality in infants and children, and therisk is directly proportional to the severity and duration ofneutropenia. To search whether infection is involved inthe neutropenia in infants and children and its potentialinvolvement of mesenchymal stromal cells, we reviewedmedical records to analyze the risk factors to acquiredneutropenia and studied whether myelopoietic growthfactor(s) secreted by mesenchymal stromal cellswas(were) inhibited by cytomegalovirus (CMV).METHODS: We reviewed 66 062 admission medicalrecords from the 5-year period from January 1, 2002 toDecember 31, 2006 to identify neutropenic patients withand without follow-up of the neutropenic course untilDecember 31, 2007. We used CMV to infect bonemarrow-derived mesenchymal stromal cells between 5and 15 passages. for 48 hours and 120 hours formeasuring growth factors in culture media and extractedDNA from mesenchymal stromal cells to analyze CMVviral load by quantitative real time polymerase chainreaction.MAIN RESULTS: After excluding patients withmalignancy, collagen disease, bone marrow failuresyndrome, prematurity, hereditary disease, congenitalneutropenia, immunodeficiency, or status post livertransplantation, we identified thrombocytosis and CMVinfection were the risk factors to prolonged acquiredneutropenia in children. The level of tumor necrosisfactor-α (TNF-α), granulocyte-macrophage colonystimulating factor (GM-CSF), interleukin-6 (IL-6) andother mediators in conditioned media of CMV-infected oruninfected mesenchymal stromal cells will be measuredand reported.CONCLUSION: CMV infection was associated withprolonged acquired neutropenia, and mesenchymalstromal cell factors might be involved in the inhibition ofmyelopoiesis. Neutropenic infants may require anti-CMVvirus therapy or modulation of mesenchymal stromalfactors in order to prevent prolonged acquiredneutropenia.FP26-8CLINICAL EXPERIENCE OF TWICE-DAILYDEFERASIROX IN TWO TERTIARY CAREHOSPITALS IN TAIWANHsiu-Hao Chang, 3,5 , Yu-Mei Liao, 1 , Meng-Yao Lu, 3 ,Pei-Chin Lin, 1 ,Yung-Li Yang, 3,4,5 , Dong-Tsamn Lin 3,4 ,Shyh-Shin Chiou, 1,2 , Shiann-Tarng Jou, 3 , Kai-Hsin Lin, 3Tai-Tsung Chang. 1,21 Department of Pediatrics, Kaohsiung Medical University Hospital; 2 KaohsiungMedical University, Kaoshiung,Taiwan; 3 Department of Pediatrics; 4 Departmentsof Laboratory Medicine, National Taiwan University Hospital, 5 GraduateInstitute of Clinical Medicine, National Taiwan University College of Medicine,Taipei, Taiwan.OBJECTIVE: Deferasirox is a newly developed once-daily oral ironchelating agent for patients with transfusion-dependent iron overload.Although it has shown promising effects in many studies, a proportionof patients are not responsive or tolerated to once-daily therapy ofdeferasirox. The aim of this study is to evaluate the efficacy ofimprovement in iron chelating and tolerability of deferasirox treatmentby twice-daily dosing on patients with transfusion-dependent ironoverload.METHODS: Patients with transfusion-dependent β-thalassemia whoshowed poor response or intolerance to once-daily deferasirox receivedtwice-daily dosing as an alternative therapy since June, 2008, inKaohsiung Medical University Hospital, and January, 2009, inNational Taiwan University Hospital. Clinical data of the patients wereobtained retrospectively by chart reviewing in these two hospitals. Theiron chelating efficacy was evaluated by the changes of serum ferritinlevels monthly. In addition, the severity of adverse effects (AEs)associated with previous once-daily deferasirox were compared withthat of twice-daily dosing.MAIN RESULTS: Eleven patients whose serum ferritin levels weremore than 2500 μg/L and received twice-daily deferasirox treatmentcontinuously at least 6 months were included for evaluation of ironchelating efficacy. In these 11 subjects, the mean serum ferritin leveldecreased from 4087.5 μg/L at baseline to 2646.2 μg/L after 6 monthstreatment (P < 0.001 by paired t test). All 11 patients showed decreasein serum ferritin levels (Mean: 1441.3 μg/L, range: 17 to 2730 μg/L).The mean dosage of deferasirox in these 11 patients was the samebetween baseline and 6 th months (36.4 mg/kg/day). One of the 11patients, after receiving twice-daily deferasirox intake for 2 months,showed an elevation of serum creatinine level above normal range,which was resolved after dosage adjustment. In another 7 patients whooriginally showed intolerance to once-daily deferasirox intake andswitched to alternative twice-daily dosing, five (71.4%) patientsexperienced less or reduced severities of AEs, which included two witharthralgia, two with liver function impairment, and one with GI upset.However, the other two patients continued to experience the same AEs,which included one with liver function impairment, and one withelevated serum amylase levels. No other new AEs were observed inany of the 18 patients after twice-daily deferasirox treatment.CONCLUSIONS: The results indicate that twice-daily deferasirox iseffective in further iron chelating and tolerability improving forpatients with transfusion-dependent β-thalassemia who were notresponsive or tolerated to once-daily dosing. Although in goodtolerance, closely monitoring the serum creatinine levels of the patientsreceiving twice-daily deferasirox is still essential.[Keywords] deferasirox, iron overload, thalassemia, twice-daily[Keywords] cytomegalovirus, neutropenia, mesenchymal stromal cell163

SL-1TYPICALLY AND ATYPICALLY DEVELOPINGCHILDREN IN MOTOR DEVELOPMENTUNDER ONE YEAR OF AGESuh-Fang Jeng, PT, ScDProfessor and Chair, School and Graduate Institute of Physical TherapyCollege of Medicine, National Taiwan University, TaiwanSL-2NORMAL AND IMPAIRMENT OF HEARING IN0-1 YEAR OLD INFANTSJiaguang Liang, M.D., PH.D.Chief and Associate Professor,Department of Otolaryngology, Puli Christian Hospital, Taiwan1. 神 經 動 作 發 展 障 礙 的 盛 行 率2. 早 期 評 估 與 早 期 介 入 的 重 要 性3. 神 經 動 作 發 展 的 理 論 : 從 神 經 成 熟 論 到 動 態 系 統理 論 與 感 知 動 作 理 論4. 早 期 神 經 動 作 發 展 評 估 簡 介(1) 新 生 兒 神 經 動 作 發 展 評 估項 目 包 括 原 始 反 射 、 動 作 型 態 與 意 識 反 應(2) 嬰 兒 神 經 動 作 發 展 評 估項 目 包 括 原 始 反 射 、 姿 勢 反 應 、 動 作 里 程碑 與 動 作 品 質6. 早 期 神 經 動 作 發 展 評 估 的 臨 床 應 用 - 以 早 產 兒為 例164

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SL-3VISUAL DEVELOPMENT AND DISORDERSBELOW ONE YEAR OF AGEWun-Tsong Chaou MD PhD.Pediatric Neurology, Puli Christian Hospital, TaiwanEvery normal infant enters life with equipmentsenabling him simultaneously to develop in body, mindand personality as a unique individual. He is subject toan array of sensory stimulations which stream into hiscentral nervous system, through receptors which copewith sensation from outside his body. Of all the senses,vision provides the most information to the brain. Theinfant's early development depends on vision, since allof the body systems require visual feedback forpractice and refinement. When the visual system isimpaired or dysfunctional, the other body systems donot have a monitoring tool to assure their smooth andtimely development.SL-4LANGUAGE AND SPEECH DEVELOPMENT:BIRTH TO ONEPaochuan TorngAssistant Professor, Department of Speech and Hearing Disorders and Sciences,National Taipei College of Nursing, Taiwan本 演 講 主 要 討 論 零 至 一 歲 兒 童 的 語 言 發 展 。 語 言 可 細分 為 說 話 (speech production)、 語 言 理 解 (languagecomprehension) 與 語 言 表 達 (language production)。 這次 的 討 論 將 以 兒 童 說 話 發 展 為 重 點 。 零 至 一 歲 兒 童 的說 話 發 展 稱 為 「 語 言 前 期 」(prelinguistics stage); 在 此時 期 , 兒 童 所 發 出 的 語 音 , 以 語 言 學 的 觀 點 並 不 代 表任 何 有 意 義 的 語 言 , 然 而 這 時 期 的 幾 個 重 要 歷 程 ,如 : 咕 咕 期 、 牙 牙 學 語 期 及 亂 語 期 , 皆 與 兒 童 將 來 語言 習 得 息 息 相 關 。 演 講 將 以 語 言 障 礙 兒 之 語 言 表 現 探討 語 言 前 期 與 後 續 延 伸 之 語 言 問 題 及 其 相 關 性 。In the early months of life, the visual system has notyet fully developed. The eye's growth is complete byage 3 and nearly one third of its growth, in diameter, iswithin the first year of life. The entire nervous systemis remaining maturing as well. Within the visualsystem, the most rapid changes occur in the lasttrimester of pregnancy and the first few months afterterm birth. Central to the understanding of visualdevelopment and it disorders needs to understand theprocesses underlying the neuronal development and theontogenesis of the nervous system.In a premature infant the visual system is not ready tofunction. The organ is lack of ability to control lightentering the eye. At birth the newborn has poor fixationability, a limited ability of color discrimination, limitedvisual fields, and rather short sighted. By 1 year of age,both near and distant acuities are good; there may besome mild farsightedness, but there is ability to focus,accommodate (shift between far and near vision tasks),and the child has depth perception. The visual systemis going to be one of the most important organs forlanguage and cognitive developing process.The Pediatrician should be concerned to see that a childwith visual disability is identified as early as possible,making proper diagnosis, perform necessaryassessment and provide proper advises for immediateand long term management. Hopefully the help for thefamily and child can be introduced in time.166

ELADVANCES IN PERINATOLOGYChiung-Lin CHEN M.DProfessor, National Taiwan University, Taiwan(A) Biology of Fetus1. The Fetus Doesn’t Accept ComplementsThe fetus is a semi-allogenic graft in its mother. It is able to thrivewithout GVH rejection, is the most enigmatie aspects ofreproduction. The importance of suppressing the innate immunesystem involving complement mediated cell killing in fetoplaceutaltolerance was suggested by discovery(1). That the human placentaproduces several inhibitors of the complement. Thus the humanplacenta is better adapted to prevent maternal complement attackduring prepnancy. Lack of these inhibtors the fetus will be abortedspontaneously.2. The Placenta PGE2 and Perturition (2)The placenta, by secreting PGE2 (and possibly other factors such asadenosine), modifies the function of key organ systems allowing thefetus to survive and develop in the aqueous environment of theuterus. During fetal development, fetal organs and metabolicpathways can mature while their function is suppressed by placentalPGE2. At birth, by ligating the cord and removing the placenta as thesource of these inhibitory substances, the newborn is able to adaptreadily to its new environment with fully-functional, mature organsystems.3. Proteome Analysis of Vernix CaseosaA white creamy substance designated Vernix caseosa (latin for“Cheese-like varnish”) covers the skin of the fetus during the lasttrimester of pregnancy. The human is the only species known toproduce this substance, and its function has been debated fordecades. Many protective functions have been proposed, such asantimicrobial protection, heat insulation, moisturization andprotection of the skin from macerating effects of the amniotic fluid.Other functions have also been suggested, such as hormonal effects,anti-flammatory effects, nutritive functions, and facilitation ofpassage through the birth canal. Furthermore, vernix has beensuggested to constitute a mechanical obstruction to bacterial passage.The composition of vernix is water (81%), lipids (9%), and proteins(10%). Altogether, 41 proteins were identified by Maria Tollinetal(3). Of these proteins, 16(39%) are involved in innate immunity and12(29%) have been demonstrated to have direct antimicrobialactivities.(B) Prematurity and IUGR(Intrauterine Growth Retardation)1. Fetal biochemisty in Growth Retardation(4)a. Cytogenetic StudiesA chromosomal abnormality high (17%), triploid (7%), trisomy 18(6%), trisomy 21 (1%), trisomy 13 (1%) translocation or deletions(2%).b. Acidosis and hypoxiac. HematologyErythropoietin increases in proportion in the degree of fetalacidemia. Erythroblast count increase platelet and leucocyte inIUGR may be decreased.d. GlucoseGlucose decrease due to impaired transfer or increased glycolysisin anaerobic metabolism to lactate.e. Lipid metabolismSGA fetuses have high triglyceride levels, reflecting reducedtriglyceride oxidation or less incorporation into body fat.f. Protein metabolismIn growth retardation there are low levels of the essential aminoacids.[Contiue↓]g. Adrenal steroidsCortisol and adreno-cortico-trophic hormone (ACTH) appear not tochange significantly.h. Thyroid functionTSH concentration is increased and thyroid hormone concentrationare reduced.2. Intrauterine Growth Restriction Affects the Preterm Infant’sHippocampusThirteen preterm infants born with IUGR after placental insufficiencywere compared with 13 infants with normal intrauterine growth agematched for gestational age. The hippocampal structural differenceswere defined using voxel-based morphometry and manualsegmentation.The specific neurobehavioral function was evaluated by theAssessment of Preterm Infants. Voxel-based morphometry detectedsignificant gray matter volume differences in the hippocampus betweenthe two groups. This finding was confirmed manual segmentation ofthe hippocampus with a reduction of hippocampal volume after IUGR.The hippocampal volum reduction was further associated withfunctional behavioral differences at term-equivalent age in all sixsubdomains of the Assessment of Preterm Infants.We conclude that hippocampal development in IUGR is altered andmight result from a combination of maternal corticosteroid hormoneexposure, hypoxemia, and micronutrient deficiency.3. Fetal Growth Restriction Is Associated With Prioritization ofUmbilical Blood Flow to the Left Hepatic Lobe at the Expense ofthe Right LobePlacental insufficiency is a major cause of impaired fetal growth andpremature birth, which, in turn, is associated with an increased risk ofchronic disease in later life. The venous perfusion of the fetal liverdiffers from that after birth in that, venous blood flows to it both fromthe splanchnic bed via the portal vein and from the placenta via theumbilical vein (Fig. 4A). Therefore, we developed a technique forblood flow measurement in the main portal stem and establishedreference ranges for this flow, showing that in uncompromised fetuses15-20% of the venous liver perfusion is of splanchnic origin.In this study, we have gone on to characterize hepatic venous perfusionin FGR and to test the hypothesis that portal blood flow maycompensate for insufficient umbilical blood flow to the liver when thelatter is diverted through the ductus venosus. We hypothesized that ingrowth-restricted fetuses portal blood flow compensates for insufficientumbilical blood flow to the liver.In 29 fetuses with fetal growth restriction (estimated fetal weight ≦5 thpercentile), weused ultrasound to measure blood flows in the umbilicalvein, ductus venosus, left portal vein, and equally affecting both liverlobes.However, portal replaced umbilical flow to the right lobe, in a mannergraded according to placental vascular resistance; in extreme cases, theright lobe received no umbilical perfusion. In fetal growth restriction,the liver suffers from venous hypoperfusion, and portal blood partiallyreplaces umbilical flow to the right lobe; this will result in right liverlobe hypoxemia.This striking prioritization in nutrient delivery of left over right lobessuggests an adaptive response to poor placental perfusion that mayhave functional consequences.167

MEP-01CHILDREN AND YOUTH PROTECTIONSERVICES IN TAIPEI & THE ROLES OFMEDICAL PROFESSIONALS IN CYPSHui-Ying HsuSection Chief of the Child and Youth Protection Department, Department ofSocial Welfare Taipei City Government, Taipei City Center for Prevention ofDomestic Violence and Sexual Assault, TaiwanMEP-02THE PARTICIPATION OF MEDICALPERSONNEL AND CRIMINAL PROCEDUREISSUES IN THE CHILD ABUSE CASEKuang-Tsung LiangProsecutor, Taiwan Taoyuan District Prosecutros Office, Taiwan一 、 前 言 :兒 童 兒 童 及 少 年 是 人 類 的 資 產 , 由 於 其 身 心 發展 未 臻 成 熟 , 因 此 提 供 妥 適 的 保 護 與 照 顧 , 是國 家 社 會 應 有 的 責 任 , 給 孩 子 一 個 更 好 的 成 長環 境 , 是 你 我 共 同 的 盼 望 與 願 意 。二 、 兒 少 保 護 概 述( 一 ) 兒 少 保 護 相 關 法 令( 二 ) 現 有 福 利 服 務( 三 ) 數 字 告 訴 我 們 真 實 樣 貌三 、 被 通 報 個 案 服 務 內 涵( 一 ) 通 報 流 程 ( 附 件 1、2)( 二 ) 受 案 服 務 處 遇 ( 附 件 3、 附 件 4)( 三 ) 服 務 案 例 分 享四 、 兒 少 保 護 網 絡 中 醫 事 人 員 的 重 要 性( 一 ) 有 心( 二 ) 有 力( 三 ) 有 資 源( 四 ) 有 網 絡五 、 結 語 : 愛 的 接 力 , 孩 子 成 長 路 上 有 你 有 我168

MEP-03CHILD MALTREATMENT: WHAT SHOULD WEDO FOR THE FUTUREYueh-Ping LiuAttending Physician, Emergency, Department National Taiwan UniversityHospital,Taiwan169

MEP-04CLINICAL CASE DISCUSSION OF CHILD ABUSEShao-Shuan HsiaDepartment of Pediatrics, Chang Gung Medical Foundation,Linkou Branch, Taiwan170