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Repetition of Apoptosis Induced by Amiloride Derivatives in Human Umbilical Vein Endothelial Cells (제대정맥 내피세포에서 Amiloride 유도체에 의한 Apoptosis 반복)

  • Park, Kyu Chang;Park, Kyu Sang;Moon, Soo Jee
    • Clinical and Experimental Pediatrics
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    • v.46 no.1
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    • pp.56-66
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    • 2003
  • Purpose : Human umbilical vein endothelial cells(HUVECs) play an important role in regulating blood flow by releasing vasoactive substances. It has been reported that endothelial impairment and dysfunction might be a primary cause of placental vascular disease, which is manifested clinically as preeclampsia in mother and intrauterine growth restriction in fetus. Furthermore, the frequency of apoptotic changes is increased in umbilical and placental tissues from growth-restricted pregnancies. However, the various mechanisms of umbilical endothelial cell apoptosis have not been broadly proposed. We investigate the effects of amiloride derivatives on apoptotic death of HUVECs and identify their ionic mechanism. Methods : HUVECs were purchased from Clonetics, and cultured on endothelial cell growth medium. MTT assay and flow cytometry were used for assessing cytotoxic effect and confirming the apoptosis. Changes in intracellular ion concentrations were measured with specific fluorescent dyes and fluorescence imaging analysis system. Results : Amiloride derivatives elicited cytotoxic effects on HUVECs with dose-dependent manners and the rank order of potency is HMA($IC_{50}\;11.2{\mu}M$), MIA>EIPA>>amiloride. HMA-induced cytotoxicity is dependent on extra- and intracellular pH, that is, increase extra- and intracellular pH augmented the cytotoxic effects of HMA. HMA dose-dependently reduced intracellular major ions, such as $K^+$ and $Cl^-$. Interestingly, the depletion of intracellular ions induced by HMA was also significantly enhanced at alkaline extracellular pH. Conclusion : Amiloride derivatives induce apoptosis of HUVECs with dose and pH dependent manners. They reduce intracellular $K^+$ and $Cl^-$ concentration, which is also extracellular pH dependent.

Clinical feature of neonatal pneumothorax induced by respiratory distress syndrome and pneumonia (호흡곤란증후군과 폐렴에 의한 신생아 기흉의 임상적 특성)

  • Jung, Ji-Sun;Park, Sang-Woo;Kim, Chun-Soo;Lee, Sang-Lak;Kwon, Tae-Chan
    • Clinical and Experimental Pediatrics
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    • v.52 no.3
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    • pp.310-314
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    • 2009
  • Purpose : Pneumothorax is an important factor responsible for increased mortality and morbidity in neonates. Here, we compared the clinical findings and prognosis for neonatal pneumothorax induced by respiratory distress syndrome (RDS) and pneumonia. Methods : Between January 2001 and December 2005, 80 patients with neonatal pneumothorax induced by RDS and pneumonia and admitted to the NICU of Dongsan Medical Center, Keimyung University, were enrolled. They were assigned to the RDS group (30 cases) or the pneumonia group (50 cases). Admission records for gestational age, onset day of life, rate of ventilatory care and thoracostomy, and prognosis were retrospectively reviewed and statistically analyzed for both groups. Results : The mean gestation age was significantly shorter in the RDS group (32.3 weeks) than in the pneumonia group (38.1 weeks) (P<0.001), and the mean onset day of life were later in the RDS group (4.6 days) than in the pneumonia group (1.8 days) (P<0.05). Rates of ventilatory care and thoracostomy were higher for the RDS group than for the pneumonia group (100% vs. 44%, and 66.7% vs. 48%, respectively). Total mortality rates and pneumothorax specific mortality rates were higher for the RDS group than for the pneumonia group (46.7% vs. 18%, P<0.01 and 33.3% vs. 16%, P<0.05, respectively). After logistic regression analysis, preterm significantly increased the mortality rate (OR 7.44, 95% CI: 1.99-27.86, P<0.005), but bilateral involvement (OR 1.17, 95% CI: 0.82-1.67, P>0.5) and the RDS group itself (OR 1.70, 95% CI: 0.52-5.54, P>0.3) did not increase mortality rates significantly. Conclusion : Our study suggests that neonatal pneumothorax in the RDS group tends to have a later onset, higher mortality rate, and needs a higher rate of thoracostomy than the pneumonia group. However, after logistic analysis, only preterm significantly and independently increased the mortality rate.

Risk factors associated with complicated methicillin-resistant Staphylococcus aureus bacteremia in neonates (신생아의 MRSA 균혈증에서 합병증 발생과 연관된 위험인자)

  • Lee, Young Jin;Kim, Hyen Jin;Byun, Shin Yun;Park, Su Eun;Park, Hee Ju
    • Clinical and Experimental Pediatrics
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    • v.53 no.2
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    • pp.173-177
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    • 2010
  • Purpose : Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen that causes nosocomial infection in NICU. It contributes to neonatal morbidity and mortality with variable complications. This study was conducted to identify the risk factors associated with complicated MRSA bacteremia in neonates. Methods : We reviewed the medical records of 44 neonates with positive blood culture for MRSA who were admitted to the NICU of Pusan National University Hospital from January 2002 to December 2007. We compared various factors of the complicated and uncomplicated MRSA bacteremia cases. Results : Of the 44 neonates, 31 were male and 13, female. The mean gestational age and birth weight were $33.2{\pm}4.9$ weeks and $1,859.9{\pm}962.2g$, respectively. Twenty-one of infants were treated with a mechanical ventilator during a mean of $8.8{\pm}13.8$ days. There were 13 cases of complicated and 31 cases of uncomplicated MRSA bacteremia. Between the 2 groups, we compared the following variables: gestational age, birth weight, ventilator use, umbilical catheter use and central catheter insertion, $O_2$ inhalation, first oral feeding day after birth, underlying disease, transfusion, and initial vancomycin use. The underlying disease and transfusion were the risk factors related to complicated MRSA bacteremia. Conclusion : Complicated MRSA bacteremia is related to underlying disease and transfusion. Since this was a retrospective study with a small sample size, it offered limited capacity to compare complicated and uncomplicated MRSA bacteremia. A prospective study with a larger population is needed to determine the exact characteristics of MRSA bacteremia in NICU.

Clinical factors causing hyponatremia in patients with mucocutaneous lymph node syndrome (가와사끼병에서 저나트륨혈증의 관련인자에 대한 임상적 고찰)

  • Kim, Soo Yeon;Kim, Hyun Jung;Choi, Jun Seok;Huh, Jae Kyung
    • Clinical and Experimental Pediatrics
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    • v.52 no.3
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    • pp.364-369
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    • 2009
  • Purpose : Clinical and laboratory findings predict a severe outcome for mucocutaneous lymph node syndrome. This study aimed to define the clinical characteristics of Kawasaki disease (KD) patients with hyponatremia and to determine the factors associated with its development. Methods : Retrospective studies were performed on 114 KD patients who received an initial high-dose intravenous immunoglobulin (IVIG, single 2 g/kg/dose) within 10 days of fever onset from January 2006 to February 2008. These patients were divided into 2 groups. Group 1 consisted of 30 (26.3%) patients with hyponatremia, and group 2 consisted of 84 (73.6%) patients without hyponatremia. Clinical manifestations, laboratory results, and echocardiographic findings were compared between the groups. Results : Group 1 patients were more likely to have a coronary artery lesion (53.3% versus 20.2%, P=0.005) and suffered from diarrhea (41.3% versus 14.1%, P=0.007). There was a higher incidence of cardiovascular involvement in group 1 patients, including coronary dilatation (46.6%), valvular regurgitation (13.3%), pericardial effusion (6.7%) and medium-sized aneurysm (6.7%). There were no coronary aneurysms in group 2 patients. Serum C-reactive protein (CRP) was significantly higher in patients with hyponatremia ($12.2{\pm}7.79$ mg/dL versus $7.3{\pm}4.7$ mg/dL, P=0.003) and IVIG-resistant patients were more common in group 1 (13.3% versus 3.6%). Conclusion : These results indicate that hyponatremia in KD occurs in patients exhibiting severe inflammation and was significantly associated with the development of coronary disease. Further studies will be necessary to confirm the pathogenic mechanisms of hyponatremia in KD patients.

Performance effectiveness of pediatric index of mortality 2 (PIM2) and pediatricrisk of mortality III (PRISM III) in pediatric patients with intensive care in single institution: Retrospective study (단일 병원에서 소아 중환자의 예후인자 예측을 위한 PIM2 (pediatric index of mortality 2)와 PRIMS III (pediatric risk of mortality)의 유효성 평가 - 후향적 조사 -)

  • Hwang, Hui Seung;Lee, Na Young;Han, Seung Beom;Kwak, Ga Young;Lee, Soo Young;Chung, Seung Yun;Kang, Jin Han;Jeong, Dae Chul
    • Clinical and Experimental Pediatrics
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    • v.51 no.11
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    • pp.1158-1164
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    • 2008
  • Purpose : To investigate the discriminative ability of pediatric index of mortality 2 (PIM2) and pediatric risk of mortality III (PRISM III) in predicting mortality in children admitted into the intensive care unit (ICU). Methods : We retrospectively analyzed variables of PIM2 and PRISM III based on medical records with children cared for in a single hospital ICU from January 2003 to December 2007. Exclusions were children who died within 2 h of admission into ICU or hopeless discharge. We used Students t test and ANOVA for general characteristics and for correlation between survivors and non-survivors for variables of PIM2 and PRISM III. In addition, we performed multiple logistic regression analysis for Hosmer-Lemeshow goodness-of-fit, receiver operating characteristic curve (ROC) for discrimination, and calculated standardized mortality ratio (SMR) for estimation of prediction. Results : We collected 193 medical records but analyzed 190 events because three children died within 2 h of ICU admission. The variables of PIM2 correlated with survival, except for the presence of post-procedure and low risk. In PRISM III, there was a significant correlation for cardiovascular/neurologic signs, arterial blood gas analysis but not for biochemical and hematologic data. Discriminatory performance by ROC showed an area under the curve 0.858 (95% confidence interval; 0.779-0.938) for PIM2, 0.798 (95% CI; 0.686-0.891) for PRISM III, respectively. Further, SMR was calculated approximately as 1 for the 2 systems, and multiple logistic regression analysis showed ${\chi}^2(13)=14.986$, P=0.308 for PIM2, ${\chi}^2(13)=12.899$, P=0.456 for PRISM III in Hosmer-Lemeshow goodness-of-fit. However, PIM2 was significant for PRISM III in the likelihood ratio test (${\chi}^2(4)=55.3$, P<0.01). Conclusion : We identified two acceptable scoring systems (PRISM III, PIM2) for the prediction of mortality in children admitted into the ICU. PIM2 was more accurate and had a better fit than PRISM III on the model tested.

Renal manifestations in tuberous sclerosis complex (결절성 경화증 환자에서의 신장 발현)

  • Jeong, Il Cheon;Kim, Ji Tae;Hwang, You Sik;Kim, Jung A;Lee, Jae Seung
    • Clinical and Experimental Pediatrics
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    • v.50 no.2
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    • pp.178-181
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    • 2007
  • Purpose : The renal manifestations of tuberous sclerosis complex (TSC) are remarkably diverse, including polycystic kidney disease, simple renal cysts, renal cell carcinomas, and angiomyolipomas. All of these occur in children as well as adults in TSC. Angiomyolipomas, which can cause spontaneous life-threatening hemorrhages, are by far the most prevalent and the greatest source of morbidity. Here, we will address our experience, adding to the literature on pediatric patients with TSC requiring evaluation and treatment for renal manifestations. Methods : A retrospective analysis was made on 19 patients in whom TSC was diagnosed between May 2001 and Oct. 2005 at Severance Hospital. All patients had clinical diagnoses of TSC as defined by the 1998 tuberous sclerosis complex consensus conference. Results : The patients consisted of 13 boys and 6 girls with a mean age of 7.3 years (range 1 to 22). The renal disease associated with TSC included angiomyolipoma in nine patients (47.4 percent), renal simple cyst in one (5.3 percent), hydronephrosis in one (5.3 percent) patient. Eight patients (42.1 percent) presented with normal kidney contours at abdominal ultrasonography. One patient underwent renal replacement therapy due to chronic renal insufficiency after nephrectomy. Hemorrhage from angiomyolipoma was not detected. Conclusion : In our review of 19 cases of TSC, renal manifestations are reported in 57.9 percent of patients. Asymptomatic angiomyolipoma associated with TSC grow gradually, although severe hemorrhages are rare. So patients with TSC should be followed up with serial computerized tomography or abdominal ultrasonography. And also, renal function should be monitored conservatively.

Comparison of growth and neuropsychological function after treatment for hematologic and oncologic diseases in monozygotic twins (일란성 쌍생아에서 혈액 및 종양 질환 치료 후 성장 및 정신신경학적 발달에 대한 비교연구)

  • Kim, Gi Hwan;Kook, Hoon;Baek, Hee Jo;Han, Dong Kyun;Song, Eun Song;Jo, Young Kook;Choi, Ic Sun;Kim, Young Ok;Kim, Chan Jong;Woo, Young Jong;Yang, Soo Jin;Hwang, Tai Ju
    • Clinical and Experimental Pediatrics
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    • v.50 no.2
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    • pp.182-189
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    • 2007
  • Purpose : The primary purpose of this study was to evaluate the growth and neuropsychologic function following treatments for pediatric hematologic and oncologic diseases. Healthy monozygotic twins served as ideal controls for comparison to exclude possible confounding factors. Methods : Seven children treated with various hematologic and oncologic diseases were included in the study: acute lymphoblastic leukemia (ALL; n=2), Diamond-Blackfan anemia twins (n=2), and aplastic anemia (n=3). The median age at the diagnosis was 5.2 (0.3-15) years. The median duration of follow-up was 7.2 (4.9-10) years. Controls were healthy monozygotic twins. Growth was measured and the percentile channels were evaluated sequentially for patients. The K-WISC III was applied and compared in 5 pairs of patients and controls. Results : Similar growth profiles were noted for the twins. The percentiles at diagnosis was 3-10 in 3, 25-50 in 2, and 50-75 in 2 cases. All patients stayed in their growth percentiles through follow-up, except for 1 patient who became obese. For IQ tests, the mean behavioral, verbal and full scale IQ scores of patients were 88.0, 93.8, and 89.8, respectively, and those from their corresponding controls were 92.2, 97.0, and 91.7 (P>0.05). However, 2 children who were treated for ALL had lower IQ scores. Conclusion : Similar growth profiles were observed in the monozygotic twins in terms of height and weight. The IQ scores of patients were similar to those of monozygotic twins. However, prophylactic CNS-directed therapy for leukemia might adversely affect the IQ scores. A further prospective study on larger number of twins is warranted.

Predicting the Progression of Chronic Renal Failure using Serum Creatinine factored for Height (소아 만성신부전의 진행 예측에 관한 연구)

  • Kim, Kyo-Sun;We, Harmon
    • Childhood Kidney Diseases
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    • v.4 no.2
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    • pp.144-153
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    • 2000
  • Purpose : Effects to predict tile progression of chronic renal failure (CRF) in children, using mathematical models based on transformations of serum creatinine (Scr) concentration, have failed. Error may be introduced by age-related variations in creatinine production rate. Height (Ht) is a reliable reference for creatinine production in children. Thus, Scr, factored for Ht, could provide a more accurate predictive model. We examined this hypothesis. Methods : The progression of of was detected in 63 children who proceeded to end-stage renal disease. Derivatives of Scr, including 1/Scr, log Scr & Ht/Scr, were defined fir the period Scr was between 2 and 5 mg/dl. Regression equation were used to predict the time, in months, to Scr > 10 mg/dl. The prediction error (PE) was defined as the predicted time minus actual time for each Scr transformation. Result : The PE for Ht/Scr was lower than the PE for either 1/Scr or log Scr (median: -0.01, -2.0 & +10.6 mos respectively; P<0.0001). For children with congenital renal diseases, the PE for Ht/Scr was also lower than for the other two transformations (median: -1.2, -3.2 & +8.2 mos respectively; P<0.0001). However, the PEs for children with glomerular diseases was not as clearly different (median: +0.9, +0.5 & +9.9 respectively). In children < 13 yrs, PE for Ht/Scr was tile lowest, while in older children, 1/Scr provided the lowest PE but not significantly different from that for Ht/Scr. The logarithmic transformation tended to predict a slower progression of CRF than actually occurred. Conclusion : Scr, floored for Ht, appears to be a useful model to predict the rate of progression of CRF, particularly in the prepubertal child with congenital renal disease.

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Prevalence of Human Papillomavirus by DNA Chip Test in Women (여성에 있어 DNA 칩검사에 의한 인유두종바이러스 감염률의 조사)

  • Kim, Jae-Woo;Kim, Yun-Tae;Kim, Dae-Sik;Choi, Seok-Cheol
    • Journal of Life Science
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    • v.18 no.12
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    • pp.1657-1664
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    • 2008
  • We determined the prevalence of human papillomavirus (HPV) by DNA chip test in 549 women and cytologic diagnosis. 237 of 549 women (43.17%) subjected with HPV DNA Chip examination were found positive for HPV. 210 (88.60%, High group) were infected with high-risk HPV types. 17 (7.17%, Low group) were infected with low-risk HPV types (6, 11, 40, 44, 70) and 17 (7.17%, Mixed group) were infected with mixed types. According to age, in their twenties, thirties, forties, fifties and over sixties, the prevalence of infection with high-risk HPV types were 1.26% (3/237), 15.61% (37/237), 31.65% (75/237), 23.21% (55/237), and 13.92% (33/237), respectively. In the Low and Mixed group, percentages of infection with HPV were significantly lower than that of the High group. On the comparison of cytologic diagnosis (224 women) by Pap smear and DNA chip positive (237 women) for HPV, 132 out of 194 cases in the High group (68.04%) suffered cervical lesions with ASCUS (atypical squamous cells of undetermined significance, 7.22%), LSIL (low grade squamous intraepithelial lesion, 15.98%), HSIL (high grade SIL, 23.20%) and ICC (invasive cervical cancer, 21.65%). The Low group (14/224 women) showed 1 case of ASCUS and 6 cases of LSIL, whereas the Mixed group (4/224 women) had only 2 cases of ASCUS. According to the HPV subtypes, the high-risk types 16 and 18 induced 26 and 7 cases of ICC, respectively, whereas other HPV subtypes induced lower or no ICC incidence. In conclusion, the present data imply that the prevalence of HPV was 43.17%, high-risk HPV type 16 is a major factor, which causes precancerous and/or cervical cancer in woman and that HPV DNA chip is an accurate and useful tool for detecting HPV.

Survival Ability of Porcine Oocytes Frozen-Thawed by Open Pulled Straw Method (Open Pulled Straw 방법에 의해 동결-융해된 돼지난자의 생존능력)

  • 김세웅;박춘근;정희태;양부근;김정익
    • Journal of Embryo Transfer
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    • v.16 no.2
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    • pp.117-125
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    • 2001
  • Vitrification of oocytes has been applied recently fur pigs, but remains elusive. The purpose of this study is to investigate the effects of vitrification in open pulled straws (OPS) on in vitro survival of porcine oocytes. When immature follicular oocytes frozen-thawed were cultured for in vitro maturation, maturation rates to metaphase-II stage were higher in oocytes with (25%) than without (15%) cumulus cells. After In vitro fertilization of oocytes frozen-thawed, the maturation rates were also significantly (P<0.05) higher in oocytes with (41%) that than without (17%) cumulus cells. However, the penetration rates were higher in oocytes without (19%) that than with (9%) cumulus. In another experiment, porcine oocytes matured in vitro were frozen and thawed for in vitro fertilization. The penetration rates were higher than in oocytes without (35%) that than with (26%) cumulus cells. However, the proportions of oocytes dead after in vitro fertilization were significantly (P<0.05) higher in oocytes with that than without cumulus cells. On the other hand, the rates of penetration and dead oocytes at 6 h after in vitro fertilization were not significant differences between oocytes with and without cumulus cells. However, the proportions of dead oocytes with (18%) and without (16%) cumulus cells were higher than in oocytes of control group (0%). These finding indicated the possible broader application for OPS, as they demonstrated that the maturation and fertilization in vitro by frozen-thawed oocytes may be accompained by cumulus cells and culture periods according to the requirements of the survival ability after freezing of mature and immature oocytes in pigs.

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