Chang Sung Son

Utility of Rapid B-Type Natriuretic Peptide Assay for Diagnosis of Symptomatic Patent Ductus Arteriosus in Preterm Infants

Objective. In preterm infants, the rapid and accurate determination of the presence of a hemodynamically significant patent ductus arteriosus (PDA) is extremely important, but this is often difficult. Plasma B-type natriuretic peptide (BNP) measurement has been reported to be a helpful aid in the diagnosis of hemodynamically significant PDA in preterm infants. The aim of our study was to investigate the usefulness of a rapid BNP assay as a diagnostic marker of symptomatic PDA (sPDA) in preterm infants. Methods. Sixty-six preterm infants, ranging from 25 to 34 gestational weeks of age, underwent clinical and echocardiographic examinations for PDA every other day from the third day of life until the disappearance of ductal flow. Blood samples were collected and plasma BNP concentrations were measured simultaneously using a commercial kit, (Triage BNP test kit; Biosite Diagnositics, San Diego, CA). When ≥2 clinically significant features of PDA were noted, and a large ductal flow was confirmed by color Doppler echocardiography, sPDA was diagnosed and treated with indomethacin. Results. On the third day after birth, the mean BNP concentration in the sPDA group (n = 23) was significantly higher than in the control group (n = 43) (2896 ± 1627 vs 208 ± 313 pg/mL). Seventeen infants (74%) in the sPDA group became asymptomatic after an initial course of indomethacin and their BNP levels concomitantly decreased. Moreover, BNP concentrations were significantly correlated with the magnitudes of the ductal shunt, such as the ratio of left atrial to aortic root diameter and the diastolic flow velocity of the left pulmonary artery (r = 0.726 and 0.877). The area under the receiver operator characteristic curve for the detection of sPDA was high: 0.997 (95% confidence interval: 0.991–1.004). The best cutoff of BNP concentration for the diagnosis of sPDA was determined to be 1110 pg/mL (sensitivity: 100%; specificity: 95.3%). Conclusion. In preterm infants, the circulating BNP levels correlated well with the clinical and echocardiographic assessments of PDA. Although not a stand-alone test, the rapid BNP assay provides valuable information for the detection of infants with sPDA that require treatment. Moreover, serial BNP measurements may be of value in determining the clinical course of PDA in preterm infants.

Utility of the Rapid B-Type Natriuretic Peptide Assay for Detection of Cardiovascular Problems in Newborn Infants with Respiratory Difficulties

Background: Because the major problems of respiratory difficulties in newborn infants are due to cardiopulmonary problems, improving the early detection and referral of newborn infants with cardiovascular problems has been considered one of the primary goals of care in the neonatal intensive care unit. Objective: To evaluate whether rapid plasma B-type natriuretic peptide (BNP) assay could be used as a screening test to detect the cardiovascular problems in newborn infants with respiratory difficulties. Methods: We studied 73 newborn infants ≧34 weeks gestational age presenting with respiratory difficulties during the first few days after birth; they were divided into a cardiovascular problem group (CP group, n = 32) and a noncardiac problem group (NP group, n = 41) according to the presence of cardiovascular problems by clinical and/or echocardiographic studies in newborn infants with respiratory difficulties. Results: On admission, the median (25–75%) BNP concentration of the CP group was significantly higher than that of the NP group [1,038 (578–1,435) vs. 240 (118–388) pg/ml, p < 0.001]. The best cutoff BNP values for differentiating the CP group were 346.0, 421.0, 570.5 and 191.5 pg/ml within 18 h, at 18–36 h, at 36–60 h and after 60 h of life, respectively. Although the plasma BNP measurement was not a single confirmative test, it was found to have a high sensitivity and a high negative predictive value for rapidly ruling out serious cardiovascular problems in neonatal respiratory difficulties. Conclusion: A rapid plasma BNP assay may be useful for detection of cardiovascular problems in newborn infants with respiratory difficulties during the first few days after birth.

Regulation of bcl-2 family in hydrogen peroxide-induced apoptosis in human leukemia HL-60 cells

Numerous types of cells have been shown to undergo apoptosis when exposed to oxidant agent such as hydrogen peroxide. In order to understand the functional relationship between the anti- and pro-apoptotic regulatory proteins in the cells under oxidant stress, we have studied the level of expression of apoptosis regulatory proteins, bcl-2 and bax, in human leukemia HL-60 cells. The exposure of HL-60 cells to different concentrations of H2O2 for 6 h resulted in a typical apoptosis of the cells as characterized by flow cytometry, cell cycle analysis, and DNA fragmantation. There was a block in G1 to S transition and apoptotic cells were mainly derived from S and G2 cells. Kinetic study demonstrated that the levels of both bcl-2-mRNA and -protein expression were decreased with the progression of cellular apoptosis whereas the level of bax-mRNA was unchanged but the expressed bax-protein was not detectable. Cycloheximide, a nonspecific translation inhibitor, did not prevent the hydrogen peroxide-mediated apoptosis in HL-60 cells. These results suggest that the regulation of bcl-2, but not of bax are important factor in the oxidative stress-induced apoptosis in HL-60 cells.

Association of serum retinol binding protein 4 with adiposity and pubertal development in Korean children and adolescents.

Retinol binding protein 4 (RBP4) has been postulated to provide a new link between obesity and insulin resistance. We aimed to assess the relationship between serum RBP4 and insulin resistance by investigating serum RBP4 levels in children and adolescents according to degree of obesity and pubertal stage. A total of 103 (30 lean, 39 overweight, 34 obese) were evaluated for serum RBP4, adiponectin, insulin, glucose and lipid profiles. RBP4 levels of obese and overweight groups were higher than those of lean group. RBP4 level was higher in pubertal group than in prepubertal group. RBP4 was positively correlated with age, height, weight, body mass index (BMI), abdominal circumference, systolic blood pressure, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol and triglyceride, and inversely with adiponectin. In the multiple linear regression analysis, RBP4 was found to be independently associated with pubertal stage, BMI and triglyceride but not with HOMA-IR. In conclusion, serum RBP4 level is related with degree of adiposity and pubertal development. The association of RBP4 with insulin resistance is supposed to be secondary to the relation between RBP4 and adipose tissue in children and adolescents.

Erythropoietin Attenuates Hyperoxia-Induced Lung Injury by Down-modulating Inflammation in Neonatal Rats

This study was done to determine whether recombinant human erythropoietin (rhEPO) treatment could attenuate hyperoxia-induced lung injury, and if so, whether this protective effect is mediated by the down-modulation of inflammation in neonatal rats. Newborn Sprague Dawley rat pups were subjected to 14 days of hyperoxia (>95% oxygen) within 10 hr after birth. Treatment with rhEPO significantly attenuated the mortality and reduced body weight gain caused by hyperoxia. With rhEPO treatment, given 3 unit/gm intraperitoneally at 4th, 5th, and 6th postnatal day, hyperoxia-induced alterations in lung pathology such as decreased radial alveolar count, increased mean linear intercept, and fibrosis were significantly improved, and the inflammatory changes such as myeloperoxidase activity and tumor necrosis factor-alpha expression were also significantly attenuated. In summary, rhEPO treatment significantly attenuated hyperoxia-induced lung injury by down-modulating the inflammatory responses in neonatal rats.

Aldosterone Modulates Cell Proliferation and Apoptosis in the Neonatal Rat Heart

In the present study, we investigated whether and how the mineralocorticoid receptor antagonist spironolactone affects cardiac growth and development through apoptosis and cell proliferation in the neonatal rat heart. Newborn rat pups were treated with spironolactone (200 mg/kg/d) for 7 days. The cell proliferation was studied by PCNA immunostaining. The treatment with spironolactone decreased proliferating myocytes by 32% (P<0.05), and reduced myocytes apoptosis by 29% (P<0.05). Immunoblot and immunohistochemistry for the expression of p38, p53, clusterin, TGF-β2, and extracellular signal-regulated kinase were performed. In the spironolactone group, p38, p53, clusterin, and TGF-β2 protein expression was significantly decreased (P<0.05). These results indicate that aldosterone inhibition in the developing rat heart induces cardiac growth impairment by decreasing proliferation and apoptosis of myocytes.

Factors to Predict Positive Results of Gonadotropin Releasing Hormone Stimulation Test in Girls with Suspected Precocious Puberty

Sometimes, the clinical findings and the results of the gonadotropin-releasing hormone (GnRH) stimulation test are inconsistent in girls with early breast development and bone age advancement. We aimed to investigate the factors predicting positive results of the GnRH stimulation test in girls with suspected central precocious puberty (CPP). We reviewed the records of 574 girls who developed breast budding before the age of 8 yr and underwent the GnRH stimulation test under the age of 9 yr. Positive results of the GnRH stimulated peak luteinizing hormone (LH) level were defined as 5 IU/L and over. Girls with the initial positive results (n = 375) showed accelerated growth, advanced bone age and higher serum basal LH, follicle-stimulating hormone, and estradiol levels, compared to those with the initial negative results (n = 199). Girls with the follow-up positive results (n = 64) showed accelerated growth and advanced bone age, compared to those with the follow-up negative results. In the binary logistic regression, the growth velocity ratio was the most significant predictive factor of positive results. We suggest that the rapid growth velocity is the most useful predictive factor for positive results in the GnRH stimulation test in girls with suspected precocious puberty.

Correlation of B-type natriuretic peptide levels and echocardiographic parameters in preterm infants with patent ductus arteriosus.

Purpose This study aimed to evaluate the correlation, according to postnatal age, between plasma B-type natriuretic peptide (BNP) levels and echocardiographic parameters for the assessment of patent ductus arteriosus (PDA) in preterm infants with respiratory distress. Methods We enrolled 42 preterm infants with respiratory distress who underwent serial echocardiographic evaluation with simultaneous plasma BNP measurements until ductal closure. The correlations between BNP levels and the following 4 representative echocardiographic parameters were studied: diameter of the ductus arteriosus (DA), ratio of the left atrial diameter to the aortic diameter (LA/Ao), ratio of the PDA diameter to the infants left pulmonary artery diameter (PDA/LPA), and the antegrade diastolic flow of LPA (DFLPA). Results BNP levels were significantly correlated to the magnitude of the ductal shunt, comprising the DA diameter, PDA/LPA ratio, LA/Ao ratio, and antegrade DFLPA for the overall study period. The earliest significant correlation, starting from postnatal day 2, was observed between the LA/Ao ratio and BNP levels. The PDA/LPA ratio and the antegrade DFLPA showed significant correlations with BNP levels postnatal day 3 onward, and with the DA diameter, postnatal day 5 onward. Conclusion BNP levels and echocardiographic parameters showed a positive correlation, but the significance of the correlations differed according to the postnatal age, especially during the first few days of life.

Mutation analysis of hepatitis B virus promoters in chronically infected children

Summary.Hepatitis B viral (HBV) infection in early childhood is one of the leading causes of chronic hepatitis and liver cirrhosis that eventually lead to hepatic carcinoma. Despite the nationwide immunization programs to curtail the vertical transmission of HBV, childhood HBV infection through mothers is still occurring in Korea. As one of the efforts to understand the childhood HBV infection in Korea, four HBV promoter sequences in the sera of the chronically infected children were analyzed. Children harbored diverse viral variants as most of the chronically infected adult patients, but the deletion mutations were rare. The dominant viral sequences in the children were highly similar to the ones in the respective mothers, indicating that the maternal viruses were most likely transmitted to the children. The mutations in X, S1, S2/S promoters did not seem to show any correlation to the severity of the disease nor ages of the children. The mutations that showed some correlation to the severity of the disease were the mutations in C promoter, but the mutations did not seem to be vertically transmitted. Finally, the children with the elevated ALT/AST levels tended to have more child-specific variants suggesting that the accumulation of host-specific mutations might be associated with the development of clinical symptoms.

Laboratory Markers in Incomplete Kawasaki Disease according to Coronary Artery Outcome

Background and Objectives We defined laboratory marker profiles typical of incomplete Kawasaki disease (iKD) during illness, especially with respect to the presence of a coronary artery abnormality such as coronary artery dilation or aneurysm. Methods This retrospective study examined the clinical and laboratory markers of patients with iKD over time, along with those of patients with complete KD (cKD) and febrile controls. Results Of 795 patients, 178 had iKD, 504 had cKD and 113 were febrile controls. During the transition from the acute to subacute phase, the age-adjusted hemoglobin levels and platelet counts were significantly lower and higher, respectively, in the subacute phase than in the acute phase in both iKD and cKD patients, which differed from those of febrile controls. Lower levels of acute and subacute age-adjusted hemoglobin levels in iKD patients (odds ratio [OR], 0.538 and 0.583; p=0.006 and 0.018, respectively) and higher subacute platelet counts in cKD patients (OR, 1.004; p=0.014) were correlated with the risk of coronary dilation. A higher acute neutrophil-to-lymphocyte ratio was associated with aneurysm only in cKD patients (OR, 1.059; p=0.044). Conclusions The iKD patients share KD-specific laboratory marker profiles in terms of complete blood cell counts and acute phase reactant levels with cKD patients. However, the factors predicting coronary dilation differ according to the phenotype; lower acute and subacute age-adjusted hemoglobin levels predict coronary dilation only in iKD patients.