• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1265-1276
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• 1998

Background : Nitric oxide(NO) is an endogenously produced free radical that plays an important role in regulating vascular tone, inhibition of platelet aggregation and white blood cell adhesion to endothelial cells, and host defense against infection. The highly reactive nature of NO with oxygen radicals suggests that it may either promote or reduce oxidant-induced cell injury in several biological pathways. Oxidant injury and interactions between pulmonary vascular endothelium and leukocytes are important in the pathogenesis of acute lung injury, including acute respiratory distress syndrome(ARDS). In ARDS, therapeutic administration of NO is a clinical condition providing exogenous NO in oxidant-induced endothelial injury. The role of exogenous NO from NO donor or the suppression of endogenous NO production was evaluated in oxidant-induced endothelial injury. Method : The oxidant injury in cultured rat lung microvascular endothelial cells(RLMVC) was induced by hydrogen peroxide generated from glucose oxidase(GO). Cell injury was evaluated by $^{51}$chromium($^{51}Cr$) release technique. NO donor, such as S-nitroso-N-acetylpenicillamine(SNAP) or sodium nitroprusside(SNP), was added to the endothelial cells as a source of exogenous NO. Endogenous production of NO was suppressed with N-monomethyl-L-arginine(L-NMMA) which is an NO synthase inhibitor. L-NMMA was also used in increased endogenous NO production induced by combined stimulation with interferon-$\gamma$(INF-$\gamma$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and lipopolysaccharide(LPS). NO generation from NO donor or from the endothelial cells was evaluated by measuring nitrite concentration. Result : $^{51}Cr$ release was $8.7{\pm}0.5%$ in GO 5 mU/ml, $14.4{\pm}2.9%$ in GO 10 mU/ml, $32.3{\pm}2.9%$ in GO 15 mU/ml, $55.5{\pm}0.3%$ in GO 20 mU/ml and $67.8{\pm}0.9%$ in GO 30 mU/ml ; it was significantly increased in GO 15 mU/ml or higher concentrations when compared with $9.6{\pm}0.7%$ in control(p < 0.05; n=6). L-NMMA(0.5 mM) did not affect the $^{51}Cr$ release by GO. Nitrite concentration was increased to $3.9{\pm}0.3\;{\mu}M$ in culture media of RLMVC treated with INF-$\gamma$ (500 U/ml), TNF-$\alpha$(150 U/ml) and LPS($1\;{\mu}g/ml$) for 24 hours ; it was significantly suppressed by the addition of L-NMMA. The presence of L-NMMA did not affect $^{51}Cr$ release induced by GO in RLMVC pretreated with INF-$\gamma$, TNF-$\alpha$ and LPS. The increase of $^{51}Cr$ release with GO(20 mU/ml) was prevented completely by adding 100 ${\mu}M$ SNAP. But the add of SNP, potassium ferrocyanate or potassium ferricyanate did not protect the oxidant injury. Nitrite accumulation was $23{\pm}1.0\;{\mu}M$ from 100 ${\mu}M$ SNAP at 4 hours in phenol red free Hanks' balanced salt solution. But nitrite was not detectable from SNP upto 1 mM The presence of SNAP did not affect the time dependent generation of hydrogen peroxide by GO in phenol red free Hanks' balanced salt solution. Conclusion : Hydrogen peroxide generated by GO causes oxidant injury in RLMVC. Exogenous NO from NO donor prevents oxidant injury, and the protective effect may be related to the ability to release NO. These results suggest that the exogenous NO may be protective on oxidant injury to the endothelium.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.522-529
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• 2005

Background : Several national societies have published guidelines for empirical antimicrobial therapy in patients with severe community-acquired pneumonia (SCAP). This study investigated the etiologies of SCAP in the Asan Medical Center and assessed the relationship between the initial empirical antimicrobial regimen and 30 day mortality rate. Method : retrospective analysis was performed on patients with SCAP admitted to the ICU between March 2002 and February 2004 in the Asan Medical Center. The basic demographic data, bacteriologic study results and initial antimicrobial regimen were examined for all patients. The clinical outcomes including the ICU length of stay, the ICU mortality rate, and 30 days mortality rates were assessed by the initial antimicrobial regimen. Results : One hundred sixteen consecutive patients were admitted to the ICU (mean age 66.5 years, 81.9 % male, 30 days mortality 28.4 %). The microbiologic diagnosis was established in 58 patients (50 %). The most common pathogens were S. pneumoniae (n=12), P. aeruginosae (n=9), K. pneumonia (n=9) and S. aureus (n=8). The initial empirical antimicrobial regimens were classified as: ${\beta}$-lactam plus macrolide; ${\beta}$-lactam plus fluoroquinolone; anti-Pseudomonal ${\beta}$-lactam plus fluoroquinolone; Aminoglycoside combination regimen; ${\beta}$-lactam plus clindamycin; and ${\beta}$-lactam alone. There were no statistical significant differences in the 30-day mortality rate according to the initial antimicrobial regimen (p = 0.682). Multivariate analysis revealed that acute renal failure, acute respiratory distress syndrome and K. pneumonae were independent risk factors related to the 30 day mortality rate. Conclusion : S. pneumoniae, P. aeruginosae, K. pneumonia and S. aureus were the most common causative pathogens in patients with SCAP and K. pneumoniae was an independent risk factor for 30 day mortality. The initial antimicrobial regimen was not associated with the 30-day mortality.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.349-359
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• 1997

Background : The signal pathways and their precise roles for acute respiratory distress syndrome caused by endotoxin (ETX) has not been established. Since there has been several in vitro experiments suggesting that activation of protein kinase C (PKC) pathway may be responsible for endotoxin-induced inflammatory reaction, we performed in vivo experiments in the rats with the hypothesis that PKC-inhibition can effectively prevent endotoxin-induced acute lung injury. Methods : We studied the role of PKC in ETX-induced ALI using PKC inhibitor (staurosporine, STP) in the rat Specific pathogen free male Sprague-Dawley weighted from 165 to 270g were used for the study. Animals were divided into the normal control (NC)-, vehicle control (VC)-, ETX-, PMA (phorbolmyristateacetate)-, STP+PMA-, and STP+ETX-group. PMA (50mg/kg) or ETX (7mg/kg) was instilled through polyethylen catheter after aseptic tracheostomy with and without STP (0.2mg/kg)-pretreatment STP was injected via tail vein 30min before intratracheal injection (IT) of PMA or ETX. Bronchoalveolar lavage (BAL) was done 3-or 6-hrs after IT of PMA or ETX respectively, to measure protein concentration, total and differential cell counts. Results : The results were as follows. The protein concentrations in BALF in the PMA- and ETX-group were very higher than that of VC-group (p<0.001). When animals were pretreated with STP, the %reduction of the protein concentration in BALF was $64.8{\pm}8.5$ and $30.4{\pm}2.5%$ in the STP+PMA- and STP+ETX-group, respectively (p = 0.028). There was no difference in the total cell counts between the PMA-and VC-group (p = 0.26). However the ETX-group showed markedly increased total cell counts as compared to the VC- (p = 0.003) and PMA-group (p = 0.0027), respectively. The total cell counts in BALF were not changed after pretreatment with STP compared to the PMA- (p = 0.22) and ETX-group (p = 0.46). The percentage of PMN, but not alveolar macrophage, was significantly elevated in the PMA-, and ETX-group. Especially in the ETX-group, the percentage of PMN was 17 times higher than that of PMA (p < 0.001). The differential cell counts was not different between the PMA and STP+PMA On the contrary the STP+ETX-group showed decreased percentage of PMN (p = 0.016). There was no significant relationship between the protein concentration and the total or differential cell counts in each group. Conclusion : Pretreatment with PKC-inhibitor (staurosporine) partially but significantly inhibited ETX-induced ALI.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1343-1352
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• 1997

Background : Heat-treated cells are known to be protected from lysis by TNF, which is considered to play a central role in the pathogenesis of sepsis-induced acute lung injury. The objective of the study was to investigate the effect of heat shock response by heat-pretreatment on the acute lung injury of the rats induced by intratracheally administered TNF-$\alpha$, Methods : We intratracheally instilled either saline or TNF (R&D, 500ng) with and without heat pretreatment in Sprague-Dawley rats weighing 250~350 g. The heated rats were raised their rectal temperature to $41^{\circ}C$ and was maintained thereafter for 13 minutes at 18 h before intratracheal administration of saline or TNF. After 5 h of intratracheal treatment, lung leak, lung myeloperoxidase activity (MPO) and heat shock proteins were measured in rats. Lung leak index was defined as counts per minute of $I^{25}$ in the right lung divided by counts per minutes of $I^{25}$ in 1.0 ml of blood. All data are expressed as means ${\pm}$SE. Results : There is no difference in acute lung leak index ($0.099{\pm}0.024$ vs $0.123{\pm}0.005$) among the rats given saline intratracheally with and without heat pretreatment, but MPO activity showed a decreased tendency in heat-pretreated rats ($4.58{\pm}0.79\;U/g$) compared with heat-unpretreated rats ($7.32{\pm}0.97\;U/g$) (P=0.064). Rats administered TNF intratracheally with heat-pretreatment had decreased lung leak index ($0.137{\pm}0.012$) and lung MPO activity ($5.51{\pm}1.04\;U/g$) compared with those of heat-unpretreated and TNF-administered rats ($0.186{\pm}0.016$, $14.34{\pm}1.22\;U/g$) (P<0.05 in each). There were no significant difference of lung leak index and MPO activity between TNF-treated rats with heat-pretreatment and saline-treated rats with and without heat-pretreatment. Conclusion : The heat shock response attenuated neutrophil recruitment and acute lung leak induced by intratracheal instillation of TNF-in rats.

• Tuberculosis and Respiratory Diseases
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• v.56 no.3
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• pp.280-288
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• 2004

Background : Lung protective strategies, using low tidal volume in ARDS, improve survival rate in ARDS. However, low tidal volume ventilation may promote alveolar de-recruitment. Therefore, alveolar recruitment is necessary to maintain arterial oxygenation and to prevent repetitive opening and closure of collapsed alveoli in lung protective strategies. There has been a recent report describing improvement in arterial oxygenation with use of recruitment maneuver. However, impact of recruitment on outcome of ARDS is unknown. We evaluated whether short-term survival difference existed in patients with ARDS, who were performed alveolar recruitment maneuver(ARM) and prone position, according to response of alveolar recruitment or not. Methods : All patients who were diagnosed with ADRS and received mechanical ventilation were included. ARM were sustained inflation($35-45cmH_2O$ CPAP for 30-40 sec.) or increasing level of PEEP. If these methods were ineffective, alveolar recruitment with prone position was done for at least 10 hours. $P_aO_2/FiO_2$(P/F) ratio was determined before and at 0.5 and 2 hours after ARM. We defined a responder if the P/F ratio was increased over 50% of baseline value. We compared 10-days and 30-days survival rate between responders and non-responders. Results : 20 patients(M:F=12:8, $63{\pm}14age$) were included. Among them, 12 patients were responders and 8 patients were non-responders. In responders, P/F ratio was increased from $92{\pm}25mmHg$ to $244{\pm}85mmHg$. In non-responders, P/F ratio increased from $138{\pm}37mmHg$ to $163{\pm}60mmHg$. Among non-responders, P/F ratio was improved over 50% in 2 patients after prone position. Overall, 14 patients were responders after ARM and prone position. The 10-days and 30-days survival rate in responders was significantly higher than in non-responders(86%, 57% in responders and 33%, 0% in non-responders)(p<0.05). There was no significant difference between responders and non-responders in age($71{\pm}11$, $60{\pm}14$), lung injury score($2.8{\pm}0.2$, $2.9{\pm}0.45$), simplified acute physiology score(SAPS) II ($35{\pm}4.6$, $34{\pm}5.7$), positive end-positive pressure level($15.6{\pm}1.9cmH_2O$, $14.5{\pm}2.1cmH_2O$). Conclusion : ARM may improve arterial oxygenation in some patients with ARDS. These responders in patients with ARDS showed significant higher 10-days and 30-days survival rate than non-responders patients with alveolar recruitment.

• Clinical and Experimental Pediatrics
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• v.52 no.4
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• pp.481-487
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• 2009

Purpose : This study investigated the clinical course and prognostic factor of very low birth weight infants (VLBWI) with hemodynamically significant congenital heart defects (CHDs). Methods : Medical records of 1,098 VLBWI with birth weight <1,500 g who had been admitted to the neonatal intensive care unit of Samsung Medical Center from October 1994 to December 2007 were reviewed retrospectively. The data for these patients with hemodynamically significant CHD (n=33) were compared with those without CHD (n=1,065). Results : The incidence of CHD was 3.0% (33 patients) 7 patients (21%) had CHD combined with the congenital abnormalities or chromosomal disorders. The most common CHD was a ventricular septal defect. The incidence of intrauterine growth retardation was higher in patients with CHD than in patients without CHD (34% vs. 20%), but there were no significant differences in gestational age, birth weight, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, severe intraventricular hemorrhage (${\geq}$Gr III), and periventricular leukomalacia. Cardiac surgery was performed on 13 patients (39%). Nine patients received staged operations, and 10 patients received early intervention. The overall mortality in patients who had CHD was higher than in the patients who did not have CHD (27% vs. 16%). In patients with CHD, congenital abnormalities or chromosomal disorders were more important factors for increased mortality (86% vs. 11%) than the degree of complexity of CHD (19% vs. 42%). Conclusion : The most important prognostic factors of VLBWI with CHD are the associated congenital abnormalities or chromosomal disorders.

• Clinical and Experimental Pediatrics
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• v.52 no.11
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• pp.1228-1233
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• 2009

Purpose : This study aimed to evaluate whether a shorter time from the arrival at a hospital to delivery is related to the occurrence of cerebral palsy in premature infants of less than 34 weeks of gestational age. Methods : We studied 142 newborns of less than 34 weeks of gestational age. The time from the arrival at the hospital to delivery was measured. The correlation between the time required for delivery and the occurrence of cerebral palsy was elucidated by diagnosing cerebral palsy in neonates using the Korean Infant Development Screening Test and neurological examination. Results : Preliminary result suggested that a shorter time from hospital arrival to delivery was related to a lower development score for gross motor activity and to a higher frequency of cerebral palsy occurrence. Moreover, it was responsible for a tendency of obtaining lower Apgar scores at 1 and 5 minutes. The shorter delivery time was associated with a higher probability of respiratory distress syndrome (RDS) occurrence when the length of delivery time was less than 6 hours and there was a higher probability of a shorter gestation period. However, the multifactor analysis revealed that there was little impact of delivery time on the occurrence of cerebral palsy. Conclusions : The length of hospital arrival time to delivery did not significantly influence the occurrence of cerebral palsy in premature infants of less than 34 weeks of gestational age.

• Neonatal Medicine
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• v.18 no.2
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• pp.197-203
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• 2011

Purpose: The purpose of this study is to compare perinatal outcomes between in vitro fertilization (IVF) twins and naturally conceived twins born to women aged 35 years or older and to provide basic information for taking care of IVF twins born to women aged 35 years or older. Methods: We reviewed the records of perinatal and neonatal outcomes in 288 IVF twins and 220 naturally conceived twins born to women aged 35 years or older between January 2001 and December 2010 at CHA Bundang Medical Center. Results: No difference was observed in the maternal ages of mothers giving birth to IVF twins and those giving birth to naturally conceived twins. Gestational ages and birth weights of IVF twins were not different from those of naturally conceived twins. Various perinatal outcomes, including gestational diabetes mellitus, pregnancy-induced hypertension, placenta previa, premature amniotic membrane rupture, and need for a Cesarean section did not differ between the 2 groups. However, the 1-min and 5-min Apgar scores (P=0.019 and P=0.045, respectively) were different between the 2 groups. The incidence of early-onset sepsis was lower in the IVF twins than in the naturally conceived twins (P=0.02). However, the 2 groups did not show any difference in the incidence of respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, and other congenital anomalies. Conclusion: The perinatal outcomes in IVF twins born to women aged 35 years or older were not significantly different from those of naturally conceived twins.

• Clinical and Experimental Pediatrics
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• v.52 no.8
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• pp.881-887
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• 2009

Purpose : The survival rate of very low birth weight infant (VLBWI) had increased as a result of advances in neonatal intensive care. We evaluated the changes in outcomes of VLBWI who admitted to the neonatal care unit of Hallym University Kangnam Sacred Heart Hospital. Methods : Retrospective review of 339 VLBWI who were born from 1st January 1997 to 31th December 2008 were performed. Outcomes including survival rate, birth weight (BW), gestational age (GA), morbidities, and mortality between period I (1997- 2003) and period II (2004-2008) were compared. Results : Overall incidence of VLBWI was 2.3% and it was significantly higher in period II(3.3%). Mean BW and GA were significantly decreased in period II (P<0.001, P=0.01). The survival rate increased from period I (59.1%) to period II (74.2%). BW-specific survival rate increased in 1,000-1,249 gm and GA-specific survival rate significantly increased in 27-28 weeks and 29-30 weeks. The incidences of respiratory distress syndrome (RDS), retinopathy of prematurity (ROP), sepsis, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, periventricular leukomalacia, and necorotizing enterocolitis were same except patent ductus arteriosus. Conclusion : The survival rate of VLBWI was increased in period II, especially in less than 1,000 gm and below 27 weeks. This may be due to recent dramatic improvement of neonatal care. But more efforts are needed to improve outcome during initial phase and to reduce long term complication such as BPD and ROP.

• Clinical and Experimental Pediatrics
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• v.50 no.12
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• pp.1200-1205
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• 2007

Purpose : We performed this study to investigate the outcome of surfactant replacement therapy (SRT) in above nearterm neonates who were required mechanical ventilatory care due to meconium aspiration pneumonia (MAP), respiratory distress syndrome (RDS) or other severe pneumonia (PN). Methods : 48 patients, gestational period ${\geq}36weeks$, who were admitted in NICU of Dongsan Medical Center, Keimyung University between July 1999 and June 2004 were enrolled. They were divided into three groups, MAP group (15 cases), RDS group (27 cases) and PN group (6 cases). All patients were received SRT and evaluated several clinical data (gestational age, oxygen index, duration of ventilator care) and outcome (complications and mortality rate) between pre-SRT and post-SRT. The mean dose of surfactant (modified bovine surfactant, Newfacten, Yuhan Co., Seoul, Korea) was 120 mg/kg. Results : Among each groups, mean pre-SRT OI was higher in MAP group ($21{\pm}3.2$) than other groups, mean duration (days) of ventilatory care and oxygen therapy were similar distributions. Compared with pre-SRT values, significant improvements (P<0.05) in mean values for FiO2 and oxygenation index were documented at 12 hours after SRT. Early complications (persistent pulmonary hypertension of newborm, pneumothorax) and survival rate were lower in MAP group. Within RDS group, earlier SRT (given before 12 hours of life) revealed significantly lower early complication rate than later SRT (given after 12 hours of life) (13.3% vs 58.3%, P<0.05) Conclusion : Our study suggested that SRT seems to be an effective therapy in above nearterm neonates with severe pulmonary disease, and earlier SRT tends to reduce complications in RDS group than later therapy.