The Youngest Survivor with Gestational Age of 215/7 Weeks.

The decision whether or not to resuscitate extremely low gestational age (GA) infants is recommended to be individualized according to antenatal counseling with parents, neonatologists, and obstetricians. A GA of 22°/7-236/7 weeks is generally considered as the lower end of the range where infants can be candidates for selective resuscitation. Below this lower end of periviable gestation, resuscitation is usually not considered and survivors are rarely reported. To date, the youngest survivor is an infant with a GA of 216/7 weeks reported in the English medical literature. Here, we report the case of a female infant, the first twin conceived through in vitro fertilization, with a GA of 215/7 weeks, who was resuscitated initially according to strong parental wishes after antenatal counseling and is still surviving at 43 months of age with fairly good neurodevelopmental outcome.

Antibacterial effect of mesenchymal stem cells against Escherichia coli is mediated by secretion of beta- defensin- 2 via toll- like receptor 4 signalling.

Recently, we demonstrated that intratracheal transplantation of human umbilical cord blood- derived mesenchymal stem cells (MSCs) attenuates Escherichia (E) coli- induced acute lung injury primarily by down- modulating inflammation and enhancing bacterial clearance iQn mice. This study was performed to elucidate the mechanism underlying the antibacterial effects of MSCs. The growth of E. coli in vitro was significantly inhibited only by MSCs or their conditioned medium with bacterial preconditioning, but not by fibroblasts or their conditioned medium. Microarray analysis identified significant up- regulation of toll- like receptors (TLR)- 2 and TLR- 4, and ß- defensin 2 (BD2) in MSCs compared with fibroblasts after E. coli exposure. The increased BD2 level and the in vitro antibacterial effects of MSCs were abolished by specific antagonist or by siRNA- mediated knockdown of TLR- 4, but not TLR- 2, and restored by BD2 supplementation. The in vivo down- modulation of the inflammatory response and enhanced bacterial clearance, increased BD2 secretion and the resultant protection against E. coli- induced pneumonia observed only with MSCs, but not fibroblasts, transplantation in mice, were abolished by knockdown of TLR- 4 with siRNA transfection. Our data indicate that BD2 secreted by the MSCs via the TLR- 4 signalling pathway is one of the critical paracrine factors mediating their microbicidal effects against E. coli, both in vitro and in vivo. Furthermore, TLR- 4 from the transplanted MSCs plays a seminal role in attenuating in vivo E. coli- induced pneumonia and the ensuing acute lung injury through both its anti- inflammatory and antibacterial effects.

Mandatory Closure Versus Nonintervention for Patent Ductus Arteriosus in Very Preterm Infants.

OBJECTIVE: To determine whether a nonintervention approach for treating hemodynamically significant patent ductus arteriosus (PDA) is associated with decreased mortality and/or morbidity compared with a mandatory closure approach in extremely low birth weight infants. STUDY DESIGN: We reviewed the medical records of 178 infants of 23-26 weeks' gestational age with PDA, requiring ventilator treatment, and with hemodynamically significant PDA ≥2 mm in size. Mandatory closure was used during period I (July 2009 to December 2011, n = 81), and nonintervention was used during period II (January 2012 to June 2014, n = 97). RESULTS: During period I, 64% of infants were first treated with indomethacin, and 82% were ultimately ligated surgically. During period II, no infant was treated with indomethacin and/or ligation. The average postnatal day of PDA closure was day 13 and day 44 during periods I and II, respectively. There was significantly more use of diuretics and fluid restriction during period II compared with period I. There was no difference in mortality or morbidities such as necrotizing enterocolitis or intraventricular hemorrhage. The incidence of bronchopulmonary dysplasia (BPD) and the propensity score adjusted OR of BPD were significantly lower during period II compared with period I. CONCLUSIONS: Despite longer PDA exposure, nonintervention was associated with significantly less BPD compared with mandatory closure. Additional study is warranted to determine the benefits and risks of non-intervention for the hemodynamically significant PDA in extremely low birth weight infants.

Intratracheal transplantation of mesenchymal stem cells simultaneously attenuates both lung and brain injuries in hyperoxic newborn rats.

BACKGROUND: Bronchopulmonary dysplasia is an independent risk factor for adverse neurodevelopmental outcomes in premature infants. We investigated whether attenuation of hyperoxic lung injury with intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells (MSCs) could simultaneously mitigate brain damage in neonatal rats. METHODS: Newborn Sprague-Dawley rats were exposed to hyperoxia or normoxia conditions for 14 d. MSCs (5 × 10(5) cells) were transplanted intratracheally at postnatal day (P) 5. At P14, lungs and brains were harvested for histological and biochemical analyses. RESULTS: Hyperoxic lung injuries, such as impaired alveolarization evident from increased mean linear intercept (MLI) and elevated inflammatory cytokine levels were significantly alleviated with MSC transplantation. Hyperoxia decreased brain weight, increased brain cell death, and induced hypomyelination. MSC transplantation significantly ameliorated hyperoxia-induced increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the dentate gyrus and reduced myelin basic protein. In correlation analyses, brain weight and myelin basic protein (MBP) were significantly inversely correlated with lung MLI and inflammatory cytokines, while TUNEL-positive brain cell number showed a significant positive correlation with lung MLI. CONCLUSION: Despite no significant improvement in short-term neurofunctional outcome, intratracheal transplantation of MSCs simultaneously attenuated hyperoxic lung and brain injuries in neonatal rats, with the extent of such attenuation being closely linked in the two tissues.

Trends in Survival and Incidence of Bronchopulmonary Dysplasia in Extremely Preterm Infants at 23-26 Weeks Gestation.

The aim of this study was to investigate the relationship between survival and incidence of bronchopulmonary dysplasia (BPD) in extremely premature infants, and identify clinical factors responsible for this association. Medical records of 350 infants at 23-26 weeks gestation from 2000 to 2005 (period I, n = 137) and 2006 to 2010 (period II, n = 213) were retrospectively reviewed. The infants were stratified into 23-24 and 25-26 weeks gestation, and the survival, BPD incidence, and clinical characteristics were analyzed. BPD was defined as oxygen dependency at 36 weeks postmenstrual age. The overall survival rate was significantly improved in period II compared to period I (80.3% vs. 70.0%, respectively; P = 0.028), especially in infants at 23-24 weeks gestation (73.9% vs. 47.4%, respectively; P = 0.001). The BPD incidence in survivors during period II (55.0%) was significantly decreased compared to period I (67.7%; P = 0.042), especially at 25-26 weeks gestation (41.7% vs. 62.3%, respectively; P = 0.008). Significantly improved survival at 23-24 weeks gestation was associated with a higher antenatal steroid use and an improved 5-minute Apgar score. A significant decrease in BPD incidence at 25-26 weeks gestation was associated with early extubation, prolonged use of less invasive continuous positive airway pressure, and reduced supplemental oxygen. Improved perinatal and neonatal care can simultaneously lead to improved survival and decreased BPD incidence in extremely premature infants.

Cell type-dependent variation in paracrine potency determines therapeutic efficacy against neonatal hyperoxic lung injury.

BACKGROUND AIMS: The aim of this study was to determine the optimal cell type for transplantation to protect against neonatal hyperoxic lung injury. To this end, the in vitro and in vivo therapeutic efficacies and paracrine potencies of human umbilical cord blood-derived mesenchymal stromal cells (HUMs), human adipose tissue-derived mesenchymal stromal cells (HAMs) and human umbilical cord blood mononuclear cells (HMNs) were compared. METHODS: Hyperoxic injury was induced in vitro in A549 cells by challenge with H2O2. Alternatively, hyperoxic injury was induced in newborn Sprague-Dawley rats in vivo by exposure to hyperoxia (90% oxygen) for 14 days. HUMs, HAMs or HMNs (5 × 10(5) cells) were given intratracheally at postnatal day 5. RESULTS: Hyperoxia-induced increases in in vitro cell death and in vivo impaired alveolarization were significantly attenuated in both the HUM and HAM groups but not in the HMN group. Hyperoxia impaired angiogenesis, increased the cell death and pulmonary macrophages and elevated inflammatory cytokine levels. These effects were significantly decreased in the HUM group but not in the HAM or HMN groups. The levels of human vascular endothelial growth factor and hepatocyte growth factor produced by donor cells were highest in HUM group, followed by HAM group and then HMN group. CONCLUSIONS: HUMs exhibited the best therapeutic efficacy and paracrine potency than HAMs or HMNs in protecting against neonatal hyperoxic lung injury. These cell type-dependent variations in therapeutic efficacy might be associated or mediated with the paracrine potency of the transplanted donor cells.

Effect of Prophylactic Palivizumab on Admission Due to Respiratory Syncytial Virus Infection in Former Very Low Birth Weight Infants with Bronchopulmonary Dysplasia.

The aim of this study was to observe the effects of prophylactic palivizumab on hospitalization secondary to respiratory syncytial virus (RSV) infection (RSVhospitalization) in former very low birth weight infants (VLBWI) with bronchopulmonary dysplasia (BPD). This study also sought to identify the risk factors of RSVhospitalizationin this particular infant population. A prospective observational study was conducted between September 2007 and April 2008 in seven Korean hospitals. Children with a history of very low birth weight, a diagnosis of BPD and who were <2 yr old at the onset of the RSV season were included in this study. Palivizumab injections were administered monthly for a maximum of five months during the RSV season. RSVhospitalization rates were reviewed, and RSVhospitalization rates between subgroups were categorized by gestational age, birth weight, and duration of ventilator care. A total of 90 subjects completed the follow-up interviews. The mean gestational age at birth was 26.1±1.7 weeks, and the mean birth weight was 889.4±222.2 g. The incidence of RSVhospitalization in the study population was 8.9% (8/90), and the mean hospital stay was 11.0±5.5 days, including one death. There were no statistically significant differences in the patients' demographic characteristics or risk factors for RSV hospitalization. When subgroup analyses were conducted, there were still no statistically significant differences. The administration of palivizumab prophylaxis during the entire RSV season is important in VLBWI with BPD, regardless of their gestational age and birth weight, or previous ventilator dependency.

Critical role of vascular endothelial growth factor secreted by mesenchymal stem cells in hyperoxic lung injury.

Intratracheal transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) protects against neonatal hyperoxic lung injury by a paracrine rather than a regenerative mechanism. However, the role of paracrine factors produced by the MSCs, such as vascular endothelial growth factor (VEGF), has not been delineated. This study examined whether VEGF secreted by MSCs plays a pivotal role in protecting against neonatal hyperoxic lung injury. VEGF was knocked down in human UCB-derived MSCs by transfection with small interfering RNA specific for human VEGF. The in vitro effects of MSCs with or without VEGF knockdown or neutralizing antibody were evaluated in a rat lung epithelial (L2) cell line challenged with H2O2. To confirm these results in vivo, newborn Sprague-Dawley rats were exposed to hyperoxia (90% O2) for 14 days. MSCs (1 × 10(5) cells) with or without VEGF knockdown were administered intratracheally at postnatal Day 5. Lungs were serially harvested for biochemical and histologic analyses. VEGF knockdown and antibody abolished the in vitro benefits of MSCs on H2O2-induced cell death and the up-regulation of inflammatory cytokines in L2 cells. VEGF knockdown also abolished the in vivo protective effects of MSCs in hyperoxic lung injury, such as the attenuation of impaired alveolarization and angiogenesis, reduction in the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive and ED-1-positive cells, and down-regulation of proinflammatory cytokine levels. Our data indicate that VEGF secreted by transplanted MSCs is one of the critical paracrine factors that play seminal roles in attenuating hyperoxic lung injuries in neonatal rats.

Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial.

OBJECTIVE: To assess the safety and feasibility of allogeneic human umbilical cord blood (hUCB)-derived mesenchymal stem cell (MSC) transplantation in preterm infants. STUDY DESIGN: In a phase I dose-escalation trial, we assessed the safety and feasibility of a single, intratracheal transplantation of hUCB-derived MSCs in preterm infants at high risk for bronchopulmonary dysplasia (BPD). The first 3 patients were given a low dose (1 × 10(7) cells/kg) of cells, and the next 6 patients were given a high dose (2 × 10(7) cells/kg). We compared their adverse outcomes, including BPD severity, with those of historical case-matched comparison group. RESULTS: Intratracheal MSC transplantation was performed in 9 preterm infants, with a mean gestational age of 25.3 ± 0.9 weeks and a mean birth weight of 793 ± 127 g, at a mean of 10.4 ± 2.6 days after birth. The treatments were well tolerated, without serious adverse effects or dose-limiting toxicity attributable to the transplantation. Levels of interleukin-6, interleukin-8, matrix metalloproteinase-9, tumor necrosis factor α, and transforming growth factor ß1 in tracheal aspirates at day 7 were significantly reduced compared with those at baseline or at day 3 posttransplantation. BPD severity was lower in the transplant recipients, and rates of other adverse outcomes did not differ between the comparison group and transplant recipients. CONCLUSION: Intratracheal transplantation of allogeneic hUCB-derived MSCs in preterm infants is safe and feasible, and warrants a larger and controlled phase II study.

A computerized asthma-specific quality of life: a novel tool for reflecting asthma control and predicting exacerbation.

BACKGROUND: Proper assessment of health-related quality of life is essential to achieve and maintain a controlled status in asthmatic patients. We developed our own computerized asthma-specific quality-of-life (cA-QOL) questionnaire based on in-depth interviews with adult asthmatic patients. In this study, we evaluated this cA-QOL in terms of the Asthma Control Test (ACT) score and Global Initiative for Asthma (GINA) guidelines as well as asthma exacerbation, and compared it with the asthma-related quality-of-life questionnaire (AQLQ). METHODS: We conducted a multicenter, prospective, observational study in 133 adult asthmatic patients recruited from 5 university hospitals in South Korea, who were randomized into 2 groups according to the operating order of the cA-QOL and AQLQ. At every visit (3-month interval), physicians evaluated asthma control status with monitoring spirometry. The self-administered cA-QOL, AQLQ(S) and ACT were completed. RESULTS: The cA-QOL scores correlated significantly with ACT and AQLQ(S) scores (r = 0.814, p < 0.001; r = 0.900, p < 0.001). The cA-QOL score was significantly lower where the ACT score was <19, in the patients with an uncontrolled asthma status according to the GINA guidelines and in those with asthma exacerbation (p < 0.001, respectively). A multivariate analysis showed that this cA-QOL was a significant parameter associated with an uncontrolled asthma status and asthma exacerbation (p < 0.001, p = 0.045, p = 0.019, respectively). CONCLUSION: The cA-QOL is a valid tool for reflecting current asthma control status and for assessment to predict the future risk of asthma exacerbation in adult asthmatics.

Elevated platelet activation in patients with chronic urticaria: a comparison between aspirin-intolerant and aspirin-tolerant groups.

BACKGROUND: Platelets are actively involved in immune inflammatory processes that release inflammatory mediators. Platelet activation has been reported in various inflammatory diseases; however, few studies have described platelet involvement in chronic urticaria (CU). OBJECTIVE: To investigate platelet-activation markers, namely P2Y12 receptor and P-selectin expression, and soluble P-selectin level in patients with aspirin-intolerant CU (AICU) and aspirin-tolerant CU (ATCU). METHODS: Forty-eight patients with CU and 25 normal controls were enrolled in this study. Aspirin intolerance in patients with CU was confirmed by an oral provocation test. P2Y12 and P-selectin expressions on platelets were measured using flow cytometry; soluble P-selectin level in plasma was measured by enzyme-linked immunosorbent assay. To study the functional effects of aspirin, platelets were treated with aspirin (2 mmol/L) and the expressions of P2Y12 and P-selectin were compared between the AICU and ATCU groups. RESULTS: The expression of P2Y12 was significantly higher in patients with CU compared with controls, whereas no significant difference was noted in the expression of P-selectin level. The levels were not significantly different according to urticaria symptom score, symptom control status, and aspirin intolerance. Soluble P-selectin level was significantly higher in the AICU group than in the ATCU group compared with controls. Aspirin did not significantly suppress P2Y12 and P-selectin expressions on platelets in the AICU group, whereas significant suppression was noted in the ATCU group. CONCLUSION: These findings suggest that increased platelet activation contributes to skin inflammation in patients with AICU and those with ATCU. The functional difference of platelets in response to aspirin may contribute to persistent skin inflammation in patients with AICU.

Association of serum periostin with aspirin-exacerbated respiratory disease.

BACKGROUND: Recent studies recommend periostin as a systemic biomarker of eosinophilic airway inflammation to predict responses to novel treatments that targets eosinophilic TH2-driven inflammation in asthmatic patients. OBJECTIVE: To investigate the clinical implications of serum periostin levels in patients with aspirin-exacerbated respiratory disease (AERD) based on its overlapping TH2-mediated pathogenesis with the eosinophilic asthma. METHODS: Serum periostin levels were measured by human periostin enzyme-linked immunosorbent assay (ELISA) in serum samples from 277 adults with asthma. Serum periostin levels were compared between patients with AERD and aspirin tolerant asthma (ATA) with other asthma phenotypes, such as severe or nonsevere asthma and eosinophilic or noneosinophilic asthma. The association of serum periostin levels with clinical parameters (including disease severity and comorbid condition) was analyzed. RESULTS: Serum periostin levels were significantly higher in patients with AERD vs ATA, patients with severe asthma vs nonsevere asthma, and patients with eosinophilic asthma vs noneosinophilic asthma (P=.005, P=.02, and P=.001, respectively). Multivariate regression analysis revealed serum periostin levels as a significant parameter to predict AERD phenotype (P=.006) together with severe asthma phenotype (P=.04). In addition, serum periostin levels correlated with blood eosinophil counts (Spearman ñ = 0.244, P<.001) and sputum eosinophil counts (Spearman ñ = 0.261, P < 0.001). Higher serum periostin levels were noted in comorbid AERD patients with more severe chronic rhinosinusitis (Lund-Mackay stages 3 and 4) than those with less severe chronic rhinosinusitis (Lund-Mackay stages 1 and 2) (P = .03). CONCLUSION: Serum periostin levels are significantly elevated in AERD patients and associated with AERD phenotype and disease severity.

A case of IgG4-related disease with bronchial asthma and chronic rhinosinusitis in Korea.

IgG4-related disease (IgG4-RD) is characterized by a systemic involvement of tumor-like lesions with IgG4-positive plasmacytes. We experienced a case of IgG4-RD developed in a patient with bronchial asthma (BA) and chronic rhinosinusitis (CRS). A 55-yr-old female patient with BA and CRS complained of both eyes and neck swelling as well as a recurrent upper respiratory infection in recent 1 yr. The serum levels of IgG4, creatinine, and pancreatic enzymes were elevated. A biopsy of the submandibular gland showed an abundant infiltration of IgG4-positive plasmacytes. Her symptoms remarkably improved after the treatment of a systemic steroid that has been maintained without recurrence. We report a rare case of IgG4-RD developed in a patient with BA and CRS.

Increased level of basophil CD203c expression predicts severe chronic urticaria.

Increased FcεR1α expression with upregulated CD203c expression on peripheral basophils is seen in patients with chronic urticaria (CU). However, there has been no published report on the association between CD203c expression level and clinical disease activity in CU patients. To investigate whether the increase of basophil activation is associated with the disease activity of CU, we measured basophil CD203c expression using a tricolor flow cytometric method in 82 CU patients and 21 normal controls. The relationship between the percentage of CD203c-expressing basophils and clinical parameters was analyzed. The mean basophil CD203c expression was significantly higher in CU patients than in healthy controls (57.5% vs 11.6%, P < 0.001). The basophil CD203c expression in severe CU patients was significantly higher than in non-severe CU (66.5% ± 23.3% vs 54.0% ± 23.3%, P = 0.033). Multiple logistic regression analysis indicated that both ≥ 72% basophil CD203c expression and urticaria activity score (UAS)≥ 13 were significant predictors of severe CU (P = 0.005 and P = 0.032, respectively). These findings suggest that the quantification of basophil activation with CD203c at baseline may be used as a potential predictor of severe CU requiring another treatment option beyond antihistamines.

The timing of surgical ligation for patent ductus arteriosus is associated with neonatal morbidity in extremely preterm infants born at 23-25 weeks of gestation.

The purpose of this study was to evaluate prognostic factors associated with surgical ligation for patent ductus arteriosus (PDA) in extremely preterm infants born at the limits of viability. Ninety infants who were born at 23-25 weeks of gestation and who received surgical ligation were included and their cases were retrospectively reviewed. Infants were classified into two different groups: survivors with no major morbidity (N), and non-survivors or survivors with any major morbidity (M). Clinical characteristics were compared between the groups. Possible prognostic factors were derived from this comparison and further tested by logistic regression analysis. The mean gestational age and the mean birth weight of M were significantly lower than those of N. Notably, the mean postnatal age at time of ligation in N was significantly later than that of the other group (17 ± 12 vs 11 ± 8 days in N and M, respectively). An adjusted analysis showed that delayed ligation (>2 weeks) was uniquely associated with a significantly decreased risk for mortality or composite morbidity after surgical ligation (OR, 0.105; 95% CI, 0.012-0.928). In conclusion, delayed surgical ligation for PDA (>2 weeks) is associated with decreased mortality or morbidities in extremely preterm infants born at 23-25 weeks of gestation.

Mesenchymal stem cells prevent hydrocephalus after severe intraventricular hemorrhage.

BACKGROUND AND PURPOSE: Severe intraventricular hemorrhage (IVH) in premature infants and the ensuing posthemorrhagic hydrocephalus cause significant mortality and neurological disabilities, and there are currently no effective therapies. This study determined whether intraventricular transplantation of human umbilical cord blood-derived mesenchymal stem cells prevents posthemorrhagic hydrocephalus development and attenuates brain damage after severe IVH in newborn rats. METHODS: To induce severe IVH, 100 µL of blood was injected into each lateral ventricle of postnatal day 4 (P4) Sprague-Dawley rats. Human umbilical cord blood-derived mesenchymal stem cells or fibroblasts (1 × 10(5)) were transplanted intraventricularly under stereotaxic guidance at P6. Serial brain MRI and behavioral function tests, such as the negative geotaxis test and rotarod test, were performed. At P32, brain tissue and cerebrospinal fluid were obtained for histological and biochemical analyses. RESULTS: Intraventricular transplantation of umbilical cord blood-derived mesenchymal stem cells, but not fibroblasts, prevented posthemorrhagic hydrocephalus development and significantly attenuated impairment on behavioral tests; the increased terminal deoxynycleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling-positive cells; increased expression of inflammatory cytokines, such as interleukin-1α, interleukin-1ß, interleukin-6, and tumor necrosis factor-α; increased astrogliosis; and reduced corpus callosal thickness and myelin basic protein expression after inducing severe IVH. CONCLUSIONS: Intraventricular transplantation of umbilical cord blood-derived mesenchymal stem cells significantly attenuated the posthemorrhagic hydrocephalus and brain injury after IVH. This neuroprotective mechanism appears to be mediated by the anti-inflammatory effects of these cells.

Clinical significance of immunoglobulin E responses to staphylococcal superantigens in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Previous studies have reported a higher prevalence of immunoglobulin E (IgE) specific for staphylococcal superantigens (SAg) in the nasal mucosa of patients with aspirin-exacerbated respiratory disease (AERD), associated with eosinophilic inflammation and leukotriene production. However, the role of SAg-specific IgE in the pathogenesis of AERD is not well understood. We evaluated the clinical significance of serum IgE specific for three types of SAg, namely staphylococcal enterotoxins A and B (SEA and SEB) and toxic shock syndrome toxin-1 (TSST-1) in AERD. METHODS: We enrolled 147 patients with AERD confirmed by a lysine-acetyl salicylic acid bronchoprovocative test and compared them with 147 patients with aspirin-tolerant asthma (ATA) and 141 healthy controls (NC). The levels of serum total IgE and SAg-specific IgE were measured using an ImmunoCAP system. Other clinical parameters were analyzed retrospectively. RESULTS: The prevalences of SEA-, SEB- and TSST-1-specific IgE in the AERD and ATA groups were significantly higher than those in the NC group (p < 0.05, respectively). The total IgE level was significantly higher in patients with AERD with high levels of SEA-specific IgE than in those with lower levels (p < 0.05), with significant positive correlations between total and SAE-specific IgE levels (p < 0.05). The PC20 methacholine level was significantly lower in patients with AERD with high levels of SEA-specific IgE, while a significantly higher eosinophil count was noted in patients with AERD with high levels of SEB-specific IgE (p < 0.05, respectively). CONCLUSIONS: Specific IgE responses to SAg may increase the serum total IgE level, airway hyperresponsiveness and eosinophil activation, leading to more severe clinical symptoms in AERD.

Antenatal betamethasone attenuates intrauterine infection-aggravated hyperoxia-induced lung injury in neonatal rats.

BACKGROUND: Intrauterine infection can exacerbate postnatal hyperoxic lung injury. We hypothesized that antenatal betamethasone treatment attenuates hyperoxic lung injury aggravated by intrauterine infection in neonatal rats. METHODS: Newborn Sprague-Dawley rats were divided into eight experimental groups according to (i) whether rats were exposed to normoxia (N) or hyperoxia (H, 85% oxygen) from postnatal day (P)1 to P14, (ii) whether antenatal betamethasone (0.2 mg/dose) or vehicle was administered to pregnant rats at gestation days (E)19 and E20, and (iii) whether intrauterine infection was induced or not antenatally. Intrauterine infection was induced by intracervical inoculation of Escherichia coli into pregnant rats on E19. We measured cytokine levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß in P1 rat lungs and performed morphometric analyses and assessed inflammatory responses in lung tissue and bronchoalveolar lavage (BAL) at P14 by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining and measurement of myeloperoxidase activity, collagen, and cytokine levels. RESULTS: Cytokine levels in P1 rat lungs were increased by intrauterine infection, and these increases were attenuated by antenatal betamethasone. Hyperoxic lung injuries, indicated by morphometric changes and an inflammatory response in the lung and BAL fluid, were aggravated by intrauterine infection at P14. This aggravation was significantly attenuated by antenatal betamethasone. CONCLUSION: Antenatal betamethasone attenuated aggravated hyperoxic lung injuries induced by intrauterine infection in neonatal rats via its anti-inflammatory actions.

Permissive hyperglycemia in extremely low birth weight infants.

The aim of this study is to evaluate the outcomes of permissive hyperglycemia up to < 300 mg/dL in extremely-low-birth-weight infants (ELBWIs). We retrospectively reviewed the medical records of 260 live-born ELBWIs at Samsung Medical Center between 2004 and 2008, grouped according to peak blood glucose level and management during the first 14 days of life. The groups were normoglycemia (N), blood glucose ≤ 200 mg/dL; permissive hyperglycemia (P), blood glucose 201-299 mg/dL without insulin treatment; treated hyperglycemia (T), blood glucose ≥ 300 mg/dL with insulin. Only 15% of patients were grouped as N, with 39% as P and 46% as T. Although P had lower birth weight, P had a similar daily calorie and glucose intake as well as urine output compared to N. There was no significant correlation between blood glucose level and urine output on day 7. Compared to N, P showed faster weight gain and similar mortality, morbidities, and long-term neurological outcomes. Permissive hyperglycemia up to < 300 mg/dL without insulin treatment during the first 14 days of life is not associated with osmotic diuresis or increased mortality or morbidities, suggesting that it is not detrimental in ELBWIs.

Quantitative in vivo detection of brain cell death after hypoxia ischemia using the lipid peak at 1.3 ppm of proton magnetic resonance spectroscopy in neonatal rats.

This study was performed to determine the accuracy of proton magnetic spectroscopy ((1)H-MRS) lipid peak as a noninvasive tool for quantitative in vivo detection of brain cell death. Seven day-old Sprague Dawley rats were subjected to 8% oxygen following a unilateral carotid artery ligation. For treatment, cycloheximide was given immediately after hypoxic ischemia (HI). Lipid peak was measured using (1)H-MRS at 24 hr after HI, and then brains were harvested for fluorocytometric analyses with annexin V/propidium iodide (PI) and fluorescent probe JC-1, and for adenosine-5'-triphosphate (ATP) and lactate. Increased lipid peak at 1.3 ppm measured with (1)H-MRS, apoptotic and necrotic cells, and loss of mitochondrial membrane potential (ΔΨ) at 24 hr after HI were significantly improved with cycloheximide treatment. Significantly reduced brain ATP and increased lactate levels observed at 24 hr after HI showed a tendency to improve without statistical significance with cycloheximide treatment. Lipid peak at 1.3 ppm showed significant positive correlation with both apoptotic and necrotic cells and loss of ΔΨ, and negative correlation with normal live cells. Lipid peak at 1.3 ppm measured by (1)H-MRS might be a sensitive and reliable diagnostic tool for quantitative in vivo detection of brain cell death after HI.