Ee-Kyung Kim

Seoul National University Hospital, Sŏul, Seoul, South Korea

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Publications (54)76.56 Total impact

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    ABSTRACT: Granulocyte colony-stimulating factor (G-CSF) is known to mobilize endothelial progenitor cells (EPCs) from bone marrow. EPCs reportedly promote neovascularization and participate in the repair of lung structure in adult animals. We tested the hypothesis that G-CSF contributes to alveolar growth by increasing the production of angiogenic growth factor in the lungs of hyperoxia-exposed neonatal mice. Neonatal mice were exposed to hyperoxia (80%) or room air (RA) for 7 days and treated with G-CSF (50 μg/kg/day) or vehicle for 5 days. Blood was subjected to flow cytometry to gate for CD45(dim/-)/Sca-1(+)/CD133(+)/vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2) to define the EPC population at day 7. The percentage of EPCs in the peripheral blood and VEGF and VEGFR2 levels in the lungs of neonatal mice exposed to hyperoxia were significantly reduced compared to those of mice kept in RA. G-CSF significantly increased EPCs in the peripheral blood, and VEGF and VEGFR2 levels in the lungs of both mice exposed to hyperoxia and mice kept in RA. G-CSF restored alveolarization inhibited by hyperoxia without altering normal alveolarization under RA. G-CSF restored alveolarization inhibited by hyperoxia in the developing lungs and this alveolarization-enhancing effect of G-CSF is associated with mobilization of EPCs and upregulation of VEGF signaling.
    Neonatology 01/2012; 101(4):278-84. · 2.57 Impact Factor
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    ABSTRACT: Peroxiredoxins (Prdx), a family of antioxidant proteins, have important defensive roles in the degenerative brain diseases and neuronal cell death in adult subjects. However, little is known in the neonatal brain. Here, we studied the developmental expression of Prdxs and their response to dexamethasone in the perinatal rat brain. Prdx 1 expression increased during late gestations and peaked at postnatal-day 1, when its expression gradually decreased. Prdx 2 expression remained largely unchanged. Prdx 6 expression continually increased as growing. Using immunohistochemistry, each Prdx showed a strong expression in the cerebral cortex and hippocampus. Prdx 1 was strongly expressed in the corpus callosum. The dexamethasone injection increased the expression of Prdx 6. In conclusion, we reveal for the first time that Prdx 1, 2 and 6 are found in abundance in the perinatal rat brain and are differentially expressed during development. The expression of Prdx 6 was affected by dexamethasone treatment.
    Free Radical Research 12/2011; 46(3):231-9. · 3.28 Impact Factor
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    ABSTRACT: Meconium obstruction (MO) of prematurity can result in increased morbidity or mortality and prolonged hospitalization if not diagnosed and treated appropriately. The aims of our study were to identify the incidence and risk factors associated with MO and to review the treatment outcomes. A retrospective analysis was undertaken of 101 extremely low birth weight infants (ELBWIs) who were born between January 1, 2007, and April 1, 2009, at Seoul National University Hospital. Prenatal and neonatal factors were compared between the MO and control groups. The treatment outcomes were also reviewed. Twenty-two (22%) patients were diagnosed as having MO. Eighteen of these patients (82%) had prenatal risk factors for MO. Respiratory distress syndrome was more prevalent in the MO group than in the control group (p = 0.001). Overall, 17 of the 22 patients (77%) were relieved with medical treatment and the rest underwent ileostomy. The times to full enteral feeding did not differ between the medically treated group and the control group. However, the surgically treated group required more time to achieve full enteral feeding, and some patients had persistent gastrointestinal problems. MO is not a rare condition in ELBWIs, and the majority of ELBWIs have prenatal risk factors. Medical management was effective, and medically manageable cases had good prognoses for subsequent feeding, whereas some surgically managed cases had persistent gastrointestinal problems.
    Neonatology 10/2011; 101(3):172-8. · 2.57 Impact Factor
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    ABSTRACT: Despite the potential importance of pulmonary artery hypertension (PAH) in preterm infants with bronchopulmonary dysplasia (BPD), little is known about the risk factors for PAH. To investigate the risk factors for PAH in preterm infants with BPD. Infants diagnosed with BPD were assigned to the PAH group or non-PAH group except for infants with mild BPD who had no PAH. PAH was diagnosed on the basis of echocardiograms demonstrating elevated right ventricle pressure beyond the postnatal age of 2 months. Logistic regression analysis was done for the multivariate assessment of the risk factors for PAH in preterm infants with moderate or severe BPD. A total of 98 infants among 145 infants with BPD were divided into a PAH group (n = 25) or non-PAH group (n = 73), while the remaining 47 infants had mild BPD with no PAH. Among the study patients, survival rate of the PAH group was significantly lower than that of the non-PAH group. Infants with PAH had more severe cases of BPD and underwent longer durations of oxygen therapy, conventional or high-frequency ventilation, and hospitalization compared to those without PAH. Low 5-min Apgar scores (≤6; relative risk (RR) 6.2; 95% confidence interval (CI) 1.4-28.0; p = 0.017) and oligohydramnios (RR 7.7; 95% CI 2.0-29.6; p = 0.030) were found to be significant risk factors for PAH according to multivariate analysis. The present study shows that oligohydramnios is a specific risk factor for PAH in preterm infants with moderate or severe BPD.
    Neonatology 07/2011; 101(1):40-6. · 2.57 Impact Factor
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    ABSTRACT: Currently, bronchopulmonary dysplasia (BPD) occurs almost exclusively in pre-term infants. In addition to prematurity, other factors like oxygen toxicity and inflammation can contribute to the pathogenesis. This study aimed to compare urinary inflammatory and oxidative stress markers between the no/mild BPD group and moderate/severe BPD group and between BPD cases with significant early lung disease like respiratory distress syndrome (RDS) ('classic' BPD) and with minimal early lung disease ('atypical' BPD). A total of 60 patients who were a gestational age < 30 weeks or a birth weight < 1250 g were included. Urine samples were obtained on the 1(st), 3(rd) and 7(th) day of life and measured the levels of leukotriene E(4) (LTE(4)) and 8-hydroxydeoxyguanosine (8-OHdG). The 8-OHdG values on the 3(rd) day showed significant correlation to duration of mechanical ventilation. The 8-OHdG levels on the 7(th) day were the independent risk factor for developing moderate/severe BPD. In 'classic' BPD, the 8-OHdG values on the 3(rd) day were higher than those of 'atypical' BPD. In 'atypical' BPD, the LTE(4) values on the 7(th) day were higher than the values in 'classic' BPD. These results suggest that oxidative DNA damage could be the crucial mechanism in the pathogenesis of current BPD and the ongoing inflammatory process could be an important mechanism in 'atypical' BPD.
    Free Radical Research 06/2011; 45(9):1024-32. · 3.28 Impact Factor
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    ABSTRACT: McKusick-Kaufman syndrome (MKS) is an autosomal recessive multiple malformation syndrome characterized by hydrometrocolpos (HMC) and postaxial polydactyly (PAP). We report a case of a female child with MKS who was transferred to the neonatal intensive care unit of Seoul National University Children's Hospital on her 15th day of life for further evaluation and management of an abdominal cystic mass. She underwent abdominal sonography, magnetic resonance imaging, genitography and cystoscopy which confirmed HMC with a transverse vaginal septum. X-rays of the hand and foot showed bony fusion of the left third and fourth metacarpal bones, right fourth dysplastic metacarpal bone and phalanx, right PAP and hypoplastic left foot with left fourth and fifth dysplastic metatarsal bones. In addition, she had soft palate cleft, mild hydronephroses of both kidneys, hypoplastic right kidney with ectopic location and mild rotation, uterine didelphys with transverse vaginal septum and low-type imperforated anus. She was temporarily treated with ultrasound-guided transurethral aspiration of the HMC. Our patient with HMC and PAP was diagnosed with MKS because she has two typical abnormality of MKS and she has no definite complications of retinal disease, learning disability, obesity and renal failure that develop in Bardet-Biedl syndrome, but not in MKS until 33 months of age. Here, we describe a case of a Korean patient with MKS.
    Korean Journal of Pediatrics 05/2011; 54(5):219-23.
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    ABSTRACT: To determine if histologic chorioamnionitis (HC) in the presence of respiratory distress syndrome (RDS) augments adverse pulmonary outcomes in extremely low birth weight (ELBW) infants. We retrospectively identified 184 ELBW infants who were born at and admitted to the neonatal intensive care units between June 2005 and June 2009. The mean gestational age of the cases was 27 ± 2 weeks, and the mean birth weight was 791 ± 147 g. A total of 88% (161/184) of patients developed bronchopulmonary dysplasia (BPD). HC was observed in 71 of 238 infants (39%). When infants were divided on the basis of the presence or absence of HC and RDS, the incidence of moderate or severe BPD and duration of oxygen requirement were greater in the HC+RDS+ group than in the HC-RDS+ or HC+RDS- groups. The combination of prenatal (HC) and postnatal (RDS) injuries increased significantly the risk for BPD. In the multivariate analysis, the significant predictors of developing BPD were low gestational age (odds ratio (OR), 0.6; confidence interval (CI), 0.4 to 0.7) and exposure to both HC and RDS (OR, 4.7; CI, 1.1 to 20.2). The HC and RDS work synergistically to induce lung injury in ELBW infants. Chorioamnionitis may interact with RDS to further increase the risk of BPD, despite either HC or RDS could not show independent significant association with BPD.
    Journal of perinatology: official journal of the California Perinatal Association 03/2011; 31(3):166-70. · 1.59 Impact Factor
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    ABSTRACT: There were many reports of longitudinal changes in the causative organisms of neonatal sepsis in Western countries but few in Asia. We aimed to study longitudinal trends in the epidemiology of neonatal sepsis at Seoul National University Children's Hospital (SNUCH), a tertiary center in Korea, and compared the results to previous studies of Western countries. The medical records of all of the neonates who were hospitalized at SNUCH from 1996 to 2005 with positive blood cultures were reviewed. We also compared the findings to previous 16-yr (1980-1995). One hundred and forty-nine organisms were identified in 147 episodes from 134 infants. In comparison with the previous 16-yr studies, there was a decrease in the number of Escherichia coli infections (16.2% vs 8.7%: odds ratio [OR] 0.495; 95% confidence interval [CI], 0.255-0.962; P = 0.035), but an increase in Staphylococcus aureus (16.6% vs 25.5%: OR 1.720; 95% CI, 1.043-2.839; P = 0.033) and fungal infections (3.3% vs 18.7%: OR 6.740; 95% CI, 2.981-15.239; P < 0.001), predominantly caused by Candida species. In conclusion, the incidence of sepsis caused by E. coli decreases, but S. aureus and fungal sepsis increases significantly. Compared with Western studies, the incidence of sepsis caused by S. aureus and fungus has remarkably increased.
    Journal of Korean medical science 02/2011; 26(2):284-9. · 0.84 Impact Factor
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    ABSTRACT: To evaluate the association between the occurrence and severity of retinopathy of prematurity (ROP) and postnatal weight gain.
    Journal of the Korean Ophthalmological Society 01/2011; 52(9):1071.
  • Journal of the Korean Society of Neonatology. 01/2011; 18(1):82.
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    ABSTRACT: To test the hypothesis that intrauterine inflammation increases prostaglandin production and may be a risk factor for persistent ductus arteriosus after therapy with indomethacin, a nonselective cyclooxygenase inhibitor. Indomethacin therapy was started after confirming ductus arteriosus within 24 hours after birth in extremely low birth weight infants. After one cycle of therapy, infants with closed ductus were classified as responders, and those with patent ductus were classified as nonresponders. Multiple logistic regression analysis was used to determine important perinatal factors associated with persistent ductus arteriosus. Immunohistochemistry with cyclooxygenase antibodies and radioimmunoassay by 6-keto prostaglandin F(1α) kit were used to determine the relationship between intrauterine inflammation and ductal patency. Forty-one infants were responders, and 37 infants were nonresponders. Responders were frequently small for gestational age; nonresponders frequently had lower gestational age, respiratory distress syndrome, and intrauterine inflammation. By multiple logistic regression analysis, respiratory distress syndrome and intrauterine inflammation were more frequent in nonresponders. Cyclooxygenase-1 expression in the umbilical arteries and plasma 6-keto prostaglandin F(1α) levels were higher in nonresponders. Respiratory distress syndrome and intrauterine inflammation were independent risk factors for persistent ductus arteriosus after indomethacin therapy in extremely low-birth weight infants. Intrauterine inflammation may have a negative influence on ductus arteriosus closure via increased cyclooxygenase-1 activity.
    The Journal of pediatrics 11/2010; 157(5):745-50.e1. · 4.02 Impact Factor
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    ABSTRACT: to investigate serial changes of lung morphology and biochemical profiles in a rat model of bronchopulmonary dysplasia (BPD) induced by intra-amniotic lipopolysaccharide (LPS) administration and postnatal hyperoxia (85%). we evaluated histological changes of the lungs and compared the levels of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and protein carbonyl in lung tissue on days 1, 7, and 14 after birth in a rat model of BPD. the inhibition of alveolarization was sustained in the LPS plus hyperoxia group from day 7 to 14, whereas alveolarization resumed in the hyperoxia group after oxygen exposure was withdrawn at day 7. Administration of LPS alone did not adversely affect lung morphometry. IL-6 levels showed transient overexpression at day 1 in the LPS-treated groups, but decreased at days 7 and 14. VEGF protein levels were elevated in the LPS-treated groups, but not in the hyper-oxia and control groups at days 1, 7, and 14. Exposure to hyperoxia affected protein carbonyl levels in the hyperoxia group at days 7 and 14. lung injury induced by intra-amniotic inflammation and postnatal hyperoxia may be due to inhibition of alveolarization without recovery even after withdrawal of oxygen.
    Journal of Perinatal Medicine 11/2010; 38(6):675-81. · 1.43 Impact Factor
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    ABSTRACT: Perinatal stroke in neonates can lead to disability in later life. However, its etiology and prognosis are poorly understood. The aim of this study was to describe clinical presentations and neurodevelopmental outcomes of our case series of perinatal stroke in Korea. Thirteen term and preterm neonates who were diagnosed with perinatal stroke in two university hospitals from March 2003 to March 2007 were enrolled. Seven term and 6 preterm neonates were diagnosed with perinatal stroke, based on the brain MRI findings. Perinatal stroke presented with seizure (4/13), perinatal distress (3/13) in term neonates, whereas stroke in preterm neonates did not present with noticeable clinical symptoms. Only one neonate had positive thrombophilic test (homozygous C677T polymorphism for MTHFR). Ten neonates had infarctions in the territory of the middle cerebral artery (MCA), and 3 neonates had borderzone infarctions between the anterior cerebral artery and MCA. Neurodevelopmental outcome was abnormal in 4 neonates. Infarction in MCA main branch or posterior limb of internal capsule showed an abnormal neurodevelopmental outcome. Our study is the first systematic study of perinatal stroke in Korea, and shows its clinical presentations and neurodevelopmental outcomes. The population-based study on incidence and prognosis of perinatal stroke in Korea is required in the future.
    Journal of Korean medical science 06/2010; 25(6):888-94. · 0.84 Impact Factor
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    ABSTRACT: The purpose of this study was to examine the clinical applicability of Doppler sonography by evaluating Doppler sonographic findings in an experimental rabbit model of necrotizing enterocolitis (NEC). Necrotizing enterocolitis was experimentally induced using a combination of endotoxin, hypoxia, and cold stress in 23 rabbits. Doppler sonography was performed to obtain the Doppler spectrum of the superior mesenteric artery. From the flow profile, the peak systolic velocity (PSV) and resistive index (RI) were calculated at 5 time sessions: initial and 1 to 2, 3 to 4, 5 to 6, and 20 to 24 hours. Animals were divided into 2 groups based on pathologic NEC scores (NEC-positive [NEC+] group versus NEC-negative [NEC-] group). Differences between the groups with regard to RI and PSV values were evaluated for each time session. Comparison of RI and PSV values between the NEC+ and NEC- groups revealed a significant increase in the PSV in the NEC+ group during the 1- to 2-hour session (P = .0199). Comparison of RI and PSV differences revealed a significant increase in RI and PSV differences in the NEC+ group during the 1- to 2-hour session (P = .0095 and .0013, respectively). In the other time sessions, there was no difference between the groups. The NEC+ group showed a significant increase in the PSV and RI during the 1- to 2-hour period.
    Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 03/2010; 29(3):379-86. · 1.40 Impact Factor
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    ABSTRACT: Periventricular-intraventricular hemorrhage (PV-IVH) is a major cause of neurological disabilities in preterm newborns. This study aimed to determine the perinatal factors associated with PV-IVH. We conducted a retrospective case-control study from preterm infants born at < or =34 weeks of gestation and admitted to Neonatal Intensive Care Units of Seoul National University Children's Hospital and Seoul National University Bundang Hospital between June 2003 and December 2007. Neonates with no cranial sonographic data or infants transferred from other centers after three days of age were excluded. Of 1,044 eligible subjects, 59 infants with PV-IVH grade 2, 3, and 4 were allocated to the case group. The control group consisted of 118 infants without PV-IVH who were matched for gestational age and birth weight to each case of PV-IVH. At the multivariate logistic regression model, metabolic acidosis (odds ratio [OR]: 6.94; 95% confidence interval [CI]: 1.12-43.23) and use of inotropes (OR: 3.70; 95% CI: 1.16-11.84) were associated with an increased risk of PV-IVH. Maternal use of antenatal corticosteroids decreases the risk of PV-IVH (OR: 0.36; 95% CI: 0.14-0.92).
    Journal of Korean medical science 03/2010; 25(3):418-24. · 0.84 Impact Factor
  • Journal of the Korean Society of Neonatology. 01/2010; 17(2):217.
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    ABSTRACT: The use of amplitude-integrated electroencephalography (aEEG) is increasing during the neonatal intensive care of preterm infants. This prospective study was designed to assess factors that affect the maturation of aEEG activity in preterm infants with a gestational age (GA) of <32 weeks. aEEGs with cerebral function monitoring were performed weekly in preterm infants, and the recordings were evaluated and scored to assess the degree of continuity, the degree of sleep-wake cycling, and the amplitude of the lower border. Subjects with any of the following conditions were excluded: intraventricular hemorrhage or periventricular leukomalacia on cranial ultrasonography, sedation, hypotension, or respiratory instability (FiO(2) >50%). The authors analyzed 207 recordings in 35 infants (GA 24-31 weeks, birth weight 440-1,980 g, postmenstrual age 25-38 weeks). At postmenstrual age 34-36 weeks, the aEEG total score was higher in preterm infants with a GA from 24 to 28 weeks than in less premature infants with a GA from 29 to 31 weeks (aEEG total score 12 vs. 10, p < 0.05). Logistic regression analysis revealed that the sleep-wake cycling was more prominent in infants with higher postnatal age (OR 3.32, 95% CI 2.40-4.59) or those receiving aminophylline (OR 3.28, 95% CI 1.06-10.08). The maturation of aEEG activity was found to be significantly correlated with postnatal age and with aminophylline use in clinically stable preterm infants. Most notably, aminophylline was found to be significantly associated with the degree of sleep-wake cycling as indicated by aEEG activity.
    Neonatology 01/2010; 98(3):245-53. · 2.57 Impact Factor
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    ABSTRACT: Spontaneous pneumomediastinum in the absence of predisposing risk factors has been rarely observed in full-term neonates. A 3-day-old neonate, delivered vaginally at term without any perinatal complications or signs of respiratory difficulty, was referred to the Seoul National University Children's Hospital because of reduced heart sound detected during routine neonatal examination. Chest computed tomography (CT) showed air collection in the anterior mediastinum. The baby developed respiratory distress on the fourth day and required supplemental oxygen. On the seventh day, there was no sign of respiratory difficulty, and x-ray examination showed no demonstrable pneumomediastinum. Hence, careful neonatal physical examination is essential during the postnatal assessment of newborns, and spontaneous pneumomediastinum should be considered when a healthy newborn presents with reduced heart sound.
    Korean Journal of Pediatrics 01/2010; 53(2).
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    ABSTRACT: The authors previously demonstrated the priming effect of intra-amniotic lipopolysaccharide (LPS) on hyperoxic lung injury in a rat model of bronchopulmonary dysplasia (BPD). To investigate the mechanism underlying this priming effect by determining biochemical profiles in a rat model of BPD. The rat model involved intra-amniotic LPS administration and postnatal hyperoxia (85%). The mRNA expressions of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), basic fibroblast growth factor (bFGF), and transforming growth factor beta(1) (TGF-beta(1)), as well as the protein levels of IL-6, VEGF, and protein carbonyl in lung tissue were compared between the LPS plus hyperoxia, the LPS only, the hyperoxia only, and the control groups. Morphometric analysis of lung tissues demonstrated that alveolarization was significantly inhibited only in the LPS plus hyperoxia group. IL-6 protein levels and its mRNA expression in the lungs were significantly increased only in the LPS plus hyperoxia group. Neither LPS nor hyperoxia increased IL-6 in the lungs independently. bFGF mRNA expression was significantly decreased in the LPS-treated groups. VEGF protein levels were significantly reduced by hyperoxia, whereas protein carbonyl levels were increased by intra-amniotic LPS or hyperoxia. No additional significant change to VEGF or protein carbonyl levels was produced by intra-amniotic LPS or hyperoxia. There were no significant differences in the mRNA expressions of VEGF, VEGFR-2, and TGF-beta(1). The priming effect of intra-amniotic LPS on hyperoxic lung injury may be associated with IL-6 elevation in the lungs.
    Neonatology 12/2009; 98(1):23-32. · 2.57 Impact Factor
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    ABSTRACT: Neonatal hypoxic-ischemic brain injury (HIE) remains a major cause of neurologic disabilities. However, many experimental therapies have shown limited successes. We assessed whether human mesenchymal stem cells (MSCs) could be transplanted in the HIE rat brain to improve neurologic disabilities. P7 SD rats were either subjected to left carotid artery ligation and hypoxic exposure [hypoxia-ischemia (HI)] or sham operation and normoxic exposure (sham). On P10, rat pubs received either PKH26-labeled MSCs or buffer via intracardial injection, resulting in four experimental groups: sham-buffer, sham-MSC, HI-buffer, and HI-MSC. Cylinder test and accelerating rotarod test were performed 14, 20, 30, and 40 d after injection. Six weeks after injection, cresyl violet and double immunofluorescence staining were performed. MSCs were transplanted to the whole brain mainly after HI. Glial fibrillary acidic protein and OX42 were more abundantly colocalized with MSC than neuronal specific nuclear protein or myelin basic protein. There were no significant differences in the total amounts and cell types between the lesioned and nonlesioned hemisphere. The lesioned hemispheric volume was decreased after HI (p = 0.012) but not restored by MSC. Neurologic performance was significantly impaired only on the cylinder test after HI (p = 0.034), and MSC transplants improved it (p = 0.010). These suggest MSC can be a candidate for the treatment of neonatal HIE.
    Pediatric Research 10/2009; 67(1):42-6. · 2.84 Impact Factor