Clinical and growth outcomes after meconium-related ileus improved with Gastrografin enema in very low birth weight infants.

BACKGROUND: Meconium-related ileus in very low birth weight infants can lead to increased morbidity or mortality and prolonged hospitalization without prompt diagnosis and treatment. This study primarily aimed to identify the incidence of and factors associated with meconium-related ileus and secondarily sought to investigate clinical and growth outcomes after water-soluble contrast media (Gastrografin) enema. METHODS: We retrospectively reviewed medical records of very low birth weight infants born between February 2009 and March 2019 in the neonatal intensive care unit of a single medical center. Perinatal factors, clinical outcomes, and growth outcomes were compared between the group with meconium-related ileus that received Gastrografin enema and the control group. RESULTS: Twenty-four (6.9%) patients were diagnosed with meconium-related ileus among 347 very low birth weight infants. All achieved successful evacuation of meconium with an average of 2.8 (range: 1-8) Gastrografin enema attempts without procedure-related complications. Initiation of Gastrografin enema was performed at mean 7.0 days (range: 2-16) after birth. Incidences of moderate to severe bronchopulmonary dysplasia were higher and the duration of mechanical ventilation and need for oxygen were longer in the meconium-related ileus group (P = 0.039, 0.046, 0.048, respectively). Meconium-related ileus infants took more time to start enteral feeding and the nothing per oral time was longer (P = 0.001 and 0.018, respectively). However, time to achieve full enteral feeding and Z-scores for weight and height at 37 weeks and at 6 months corrected age did not differ between the two groups. CONCLUSIONS: Gastrografin enema in very low birth weight infants with meconium-related ileus was an effective and safe medical management. Following Gastrografin enema, very low birth weight infants with meconium-related ileus achieved similar subsequent feeding progress and similar growth levels as the control groups without meconium-related ileus.

Incidence, Clinical Characteristics, and Genotype Distribution of Rotavirus in a Neonatal Intensive Care Unit 5 Years After Introducing Rotavirus Vaccine.

BACKGROUND: Rotavirus (RV) is a common cause of viral gastroenteritis in children worldwide. We aimed to investigate the incidence, symptoms, and genotype of RV infection in a neonatal intensive care unit (NICU) in South Korea 5 years after the introduction of RV vaccination to evaluate its effect on newborn infants. METHODS: A total of 431 fecal specimens were collected from patients admitted to NICU between April 20, 2012 and September 10, 2013. Enzyme-linked immunoassays were used to detect RV antigen. Nested multiplex polymerase chain reaction was used for genotyping. RESULTS: The overall incidence of RV infection was 43.9% and was significantly higher in preterm infants, infants born in the study hospital, low birth weight infants, and cesarean births (P < 0.05). Symptoms of diarrhea, poor feeding, abdominal distension, and apnea were significantly higher in infants with RV infection than those without infection. RV infection gradually increased depending on infant care at home, postpartum clinic, or hospital (26.0, 45.1, and 60.2%, respectively; P = 0.000). The dominant RV genotype in the NICU was G4P[6] at 95.4%. CONCLUSION: Current RV vaccines did not affect the incidence of RV infection in newborn and preterm infants in the NICU. Most RV-positive patients in the NICU had symptoms, and the incidence of RV infection was relatively higher in hospitals and postpartum clinics with group life than home. The dominant RV genotype was G4P[6] across study groups.

Characterization of Rotavirus Infection in Hospitalized Children under 5 with Acute Gastroenteritis 5 Years after Introducing the Rotavirus Vaccines in South Korea.

We herein characterized rotavirus infection in hospitalized children under 5 years of age with gastroenteritis after introducing rotavirus vaccines in South Korea from 20 February 2012, to 31 March 2013. Enzyme-linked fluorescent immunoassay was performed to detect rotavirus antigens. G and P genotyping was performed using nested multiplex PCR. For the failed PCR samples, sequencing was conducted. We performed a test-negative case-control study to estimate vaccine effectiveness. Vaccine effectiveness was measured using a multivariate logistic regression model. Rotavirus was detected in 16 (13.2%) of the 121 patients, with a seasonal peak in April 2012. The dominant genotypes detected were G3P[8] (33.3%) and G4P[6] (26.7%), and vaccine effectiveness against rotavirus hospitalization was 84.9% [95% CI: 23.2−97.0] in the complete vaccinated group. A higher prevalence of rotavirus infection was observed among children with siblings than those without siblings (p < 0.001). Also, the presence of siblings was significantly associated with a history of nonvaccination (p < 0.001). In conclusion, the prevalence of rotavirus followed a decreasing trend, and there was no evidence of emergences of nonvaccine-type strains. Vaccine effectiveness against rotavirus hospitalization was 84.9%. Although children with siblings were more susceptible to rotavirus infection, they were less likely to receive vaccination against rotavirus.

Treadmill exercise ameliorates ethanol with lipopolysaccharide and carbon tetrachloride-mediated liver injury in mice.

We reported that application of ethanol with lipopolysaccharide (LPS) and carbon tetrachloride (CCl4) enhanced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level. In the current experiment, the protective effect of treadmill running on liver injury caused by ethanol with LPS and CCl4 in mice was studied. Liver injury severity was determined by measuring ALT and AST level in the blood. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, immunohistochemistry for caspase-3, and Western blotting for Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2) were performed to indicate hepatocyte apoptosis. In addition, to understand the mechanism, 5'-adenosine monophosphate-activated protein kinase (AMPK) phosphorylation was studied by Western blotting. Treadmill exercise ameliorated ethanol with LPS and CCl4-mediated elevation of ALT and AST level. Treadmill exercise suppressed ethanol with LPS and CCl4-mediated elevation of the TUNEL-positive cell number and cleaved caspase-3 expression. Treadmill exercise suppressed ethanol with LPS and CCl4-mediated elevation of Bax expression and increased Bcl-2 expression suppressed by application of ethanol with LPS and CCl4. Treadmill exercise enhanced AMPK phosphorylation which was suppressed by application of ethanol with LPS and CCl4. Treadmill exercise has the effect of reducing liver damage caused by alcohol and or drug addiction.

Resistance Exercise Improves Spatial Learning Ability Through Phosphorylation of 5'-Adenosine Monophosphate-Activated Protein Kinase in Parkinson Disease Mice.

PURPOSE: Exercise is a representative noninvasive treatment that can be applied to various diseases. We studied the effect of resistance exercise on motor function and spatial learning ability in Parkinson disease (PD) mice. METHODS: The rotarod test and beam walking test were conducted to evaluate the effect of resistance exercise on motor function, and the Morris water maze test was conducted to examine the effect of resistance exercise on spatial learning ability. The effect of resistance exercise on brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) expression and 5'-adenosine monophosphate-activated protein kinase (AMPK) phosphorylation was investigated by Western blot analysis. New cell generation was confirmed by immunohistochemistry for 5-bromo-2'-deoxyuridine. RESULTS: Resistance exercise improved coordination, balance, and spatial learning ability in PD mice. Resistance exercise enhanced new cell production, BDNF and TrkB expression, and AMPK phosphorylation in PD mice. The effect of such resistance exercise was similar to that of levodopa application. CONCLUSION: In PD-induced mice, resistance exercise enhanced AMPK phosphorylation to increase BDNF expression and new neuron generation, thereby improving spatial learning ability. Resistance exercise is believed to help improve symptoms of PD.

Feasibility study on stereotactic radiotherapy for total pulmonary vein isolation in a canine model.

We tested the feasibility of pulmonary vein (PV) and left atrial (LA) posterior wall isolation using non-invasive stereotactic ablative body radiotherapy (SABR) and investigated pathological changes in irradiated lesions in a canine model. Seven male Mongrel dogs received single-fraction 33 Gy SABR. We designed the en-bloc circular target of total PVs and LA posterior wall to avoid the esophagus. The circular box lesion included the LA roof and ridge, low posterior wall, and posterior interatrial septum. At 6 weeks or 4 months post-SABR, electrical isolation of the SABR lesion was confirmed using LA posterior wall pacing, and histopathological review was performed. Electrical isolation of all PVs and the LA posterior wall was achieved in three of five dogs in the 4-month group. There was one target failure and one sudden death at 15 weeks. Although two dogs in the 6-week group failed to achieve electrical lesion isolation, the irradiated atrial myocardium showed diffuse hemorrhage with inflammatory cell infiltration. In successfully isolated 4-month model dogs, we observed transmural fibrotic scarring with extensive fibrosis on irradiated atrial tissue. The findings suggest that this novel circular box-design radiotherapy technique using SABR could be applied to humans after further studies are conducted to confirm safety.

Early Changes in Rat Heart After High-Dose Irradiation: Implications for Antiarrhythmic Effects of Cardiac Radioablation.

Background Noninvasive cardiac radioablation is employed to treat ventricular arrhythmia. However, myocardial changes leading to early-period antiarrhythmic effects induced by high-dose irradiation are unknown. This study investigated dose-responsive histologic, ultrastructural, and functional changes within 1 month after irradiation in rat heart. Methods and Results Whole hearts of wild-type Lewis rats (N=95) were irradiated with single fraction 20, 25, 30, 40, or 50 Gy and explanted at 1 day or 1, 2, 3, or 4 weeks' postirradiation. Microscopic pathologic changes of cardiac structures by light microscope with immunohistopathologic staining, ultrastructure by electron microscopy, and functional evaluation by ECG and echocardiography were studied. Despite high-dose irradiation, no myocardial necrosis and apoptosis were observed. Intercalated discs were widened and disrupted, forming uneven and twisted junctions between adjacent myocytes. Diffuse vacuolization peaked at 3 weeks, suggesting irradiation dose-responsiveness, which was correlated with interstitial and intracellular edema. CD68 immunostaining accompanying vacuolization suggested mononuclear cell infiltration. These changes were prominent in working myocardium but not cardiac conduction tissue. Intracardiac conduction represented by PR and QTc intervals on ECG was delayed compared with baseline measurements. ST segment was initially depressed and gradually elevated. Ventricular chamber dimensions and function remained intact without pericardial effusion. Conclusions Mononuclear cell-related intracellular and extracellular edema with diffuse vacuolization and intercalated disc widening were observed within 1 month after high-dose irradiation. ECG indicated intracardiac conduction delay with prominent ST-segment changes. These observations suggest that early antiarrhythmic effects after cardiac radioablation result from conduction disturbances and membrane potential alterations without necrosis.

Risk factors for neonatal infections in full-term babies in South Korea.

PURPOSE: Since 1997, private postnatal care facilities (San-hu-jo-ri-won in Korean) have emerged to take the role of the family. As a result, neonates are now exposed to many people and are very vulnerable to infection. However, there has been no study on the influence of postnatal care facilities on neonatal infection. The aim of this study was to determine the risk factors of neonatal infection in full-term babies in Korea. MATERIALS AND METHODS: We followed up 556 pregnant women and their babies for 4 weeks after their births at 2 hospitals in Seoul and Daejeon from October 2004 to September 2005. Among 512 full-term babies, 58 had infectious diseases. To determine the risk factors for infection, 53 infected neonates at 4-28 days of life and 413 healthy neonates were compared. RESULTS: The incidence of neonatal infection at 4 to 28 days after birth was 10.5%. After adjusting the related factors, the number of siblings (OR = 2.05, 95% CI = 1.13-3.71 for 1 or more) and postnatal care facilities or home aides (OR = 1.91, 95% CI = 1.07-3.45) were significant risk factors. Formula or mixed feeding (OR = 1.66, 95% CI = 0.91-3.04) increased the risk of neonatal infection but it was not statistically significant. CONCLUSION: When the newborns had siblings, stayed at postnatal care facilities, or were cared for by home aides, the risk of neonatal infections significantly increased. Further research on the feeding effect on neonatal infection and evaluation of prevention efforts are needed.

Ulinastatin inhibits cerebral ischemia-induced apoptosis in the hippocampus of gerbils.

Ulinastatin is a urinary trypsin inhibitor, originally extracted and purified from human urine. Ulinastatin has cytoprotective effects against ischemic injury in several organs. In the present study, the neuroprotective effects of ulinastatin following ischemic cerebral injury in the hippocampus of gerbils was investigated. To induce transient global ischemia in gerbils, the common carotid arteries were occluded using aneurysm clips for 5 min, and the clips were then removed. Ulinastatin was subcutaneously injected into the gerbils once a day for 7 days at doses of 50,000 or 100,000 U/kg. The gerbils were confronted with a step-down avoidance task, following which tissue samples from the gerbils were examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, western blot analysis for B-cell lymphoma (Bcl-2) and Bcl-2-associated X protein (Bax), immunohistochemistry for caspase-3 and immunofluorescence for 5-bromo-2'-deoxyuridine. The numbers of TUNEL-positive and caspase-3-positive cells in the hippocampal CA1 region increased following cerebral ischemia. The expression of Bax in the hippocampus increased, while the expression of Bcl-2 in the hippocampus decreased following cerebral ischemia. These results confirmed that apoptosis in the hippocampus was enhanced following cerebral ischemia in gerbils. The levels of cell proliferation in the hippocampal dentate gyrus were also enhanced by ischemia, which is possibly an adaptive mechanism to compensate for excessive levels of apoptosis. Ulinastatin treatment inhibited ischemia-induced apoptosis by suppressing apoptosis-associated molecules, and thus ameliorated ischemia-induced short-term memory impairment. The cell proliferation in the hippocampus was also suppressed following ulinastatin treatment. These results suggested the use of ulinastatin as a therapeutic agent for patients with cerebral stroke.

Ulinastatin suppresses lipopolysaccharide-induced prostaglandin E2 synthesis and nitric oxide production through the downregulation of nuclear factor­κB in BV2 mouse microglial cells.

Ulinastatin is an intrinsic serine-protease urinary trypsin inhibitor that can be extracted and purified from human urine. Urinary trypsin inhibitors are widely used to treat patients with acute inflammatory disorders, such as shock and pancreatitis. However, although the anti-inflammatory activities of urinary trypsin inhibitors have been investigated, the mechanisms underlying their actions are not yet fully understood. In the present study, we evaluated the effect of ulinastatin on lipopolysaccharide (LPS)-induced inflammation in relation with nuclear factor-κB (NF-κB) activation using BV2 mouse microglial cells. To accomplish this, we performed a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis, electrophoretic mobility gel shift assay (EMSA), prostaglandin E(2) (PGE(2)) immunoassay and nitric oxide (NO) detection. The results demonstrated that ulinastatin suppressed PGE2 synthesis and NO production by inhibiting the LPS-induced mRNA and protein expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) in BV2 mouse microglial cells. Ulinastatin suppressed the activation of NF-κB in the nucleus. These findings demonstrate that ulinastatin exerts analgesic and anti-inflammatory effects that possibly occur via the suppression of COX-2 and iNOS expression through the downregulation of NF-κB activity.

Epidemiology of respiratory syncytial virus infection in infants born at less than thirty-five weeks of gestational age.

BACKGROUND: The aims of this study were to observe the respiratory syncytial virus (RSV) hospitalization rate and to identify the risk factors for hospitalization for RSV infection among infants in Korea born at <35 weeks of gestational age and who had not previously received palivizumab. METHODS: We conducted a study over a 2.5-year period (between April 2007 and September 2009) that included premature infants (<35 weeks of gestational age) who underwent follow-up during 1 year after discharge from the neonatal intensive care unit. Demographic information was collected for each subject at baseline, and the reasons for hospitalization were obtained during the 1-year follow-up period. RESULTS: The study population included 1022 subjects who completed follow-up interviews. Eight hundred seventeen infants were included in analysis for RSV hospitalization. Excluded from the study were 167 subjects with chronic lung disease who had received palivizumab prophylaxis and 38 subjects who were not tested for RSV. The overall incidence of RSV hospitalization in the group that did not receive palivizumab was 4.5% (37 of 817 patients). Independent risk factors associated with RSV hospitalization were multiple gestation (P = 0.022) and longer duration of mechanical ventilation in the neonatal intensive care unit (P = 0.039). CONCLUSION: This study showed the epidemiology and risk factors of RSV hospitalization in preterm infants in Korea. RSV infection was one of the main causes of hospitalization after discharge from the neonatal intensive care unit in patients born at <35 weeks of gestational age.

Neonatal innate immunity and Toll-like receptor.

The innate immune response is the first line of defense against microbial infections. Innate immunity is made up of the surface barrier, cellular immunity and humoral immunity. In newborn, immunologic function and demands are different to adults. Neonatal innate immunity specifically suppresses Th1-type immune responses, and not Th2-type immune responses, which are enhanced. And the impaired response of macrophages is associated with the defective innate immunity in newborn period. Toll-like receptors (TLRs) play a key roles in the detection of invading pathogens and in the induction of innate immune responses. In newborn, the expression of TLRs is age dependent, so preterm has low expression of TLRs. Also, there are defects in signaling pathways downstream of TLRs. As a consequence, the defects of TLRs activity cause the susceptibility to infection in the neonatal period.

Parental awareness and perception for correct use of child occupant restraints in Korea.

OBJECTIVE: To determine the rate of correct use of child occupant restraints (CORs) and to evaluate the parental awareness and perception associated with the use of CORs. METHODS: A cross-sectional survey using self-report questionnaires was performed at 10 different hospitals. A total of 1573 parents and 2209 of their children 6 years of age or younger were studied. RESULTS: The overall percentage of parents using CORs or adult seat belt was 57.7 percent. However, only 44.4 percent of those parents, which corresponds to 25.6 percent of all parents recruited, were correctly using the restraints for their children. The overall percentage of children using CORs or adult seat belt was 53 percent. However, the percentage of children correctly using the restraints was 14.3 percent for infants (<12 months of age), 42 percent for children one years old, 43.8 percent for children 2 years old, 28.7 percent for children 3 years old, 18.9 percent for children 4 years old, 13.9 percent for children 5 years old, and 10.5 percent for children 6 years old. The logistic regression analysis revealed that the mother's level of education, number of children in each household, child's age when parents started to use the CORs, and parental awareness about the fine for violation of car seat laws were the most influential variables associated with the correct use of CORs. The rates of correct use of CORs and parental preferences about CORs, respectively, differed by ages of their children. Most parents showed a negative perception of placing children in the front passenger seat. However, many parents were prematurely using adult seat belts for children without realizing the risk of injury. CONCLUSION: More aggressive educational campaigns and increased enforcement of the car seat laws are needed to improve the awareness of parents on the efficacy of CORs.