• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.182-195
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• 2001

Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$l_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$1_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.

• Clinical and Experimental Pediatrics
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• v.52 no.11
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• pp.1260-1266
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• 2009

Purpose : Idiopathic nephrotic syndrome (NS) can be clinically classified as steroid-sensitive and steroid-resistant. The detailed mechanism of glucocorticoid action in NS is currently unknown. Methods : In this study, we investigated 3 known single nucleotide polymorphisms (SNPs) (ER22/23EK, N363S, and BclI) of the glucocorticoid receptor gene (the NR3C1 gene) in 190 children with NS using polymerase chain reaction-restriction fragment length polymorphism and analyzed the correlation between the genotypes and clinicopathologic features of the patients. Results : Eighty patients (42.1%) were initial steroid nonresponders, of which 31 (16.3% of the total) developed end-stage renal disease during follow-up. Renal biopsy findings of 133 patients were available, of which 36 (31.9%) showed minimal changes in NS and 77 (68.1%) had focal segmental glomerulosclerosis. The distribution of the BclI genotypes was comparable between the patient and control groups, and the G allele frequencies in both the groups were almost the same. The ER22/23EK and N363S genotypes were homogenous as ER/ER and NN, respectively, in all the patients and in 100 control subjects. The BclI genotype showed no correlation with the NS onset age, initial steroid responsiveness, renal pathologic findings, or progression to end-stage renal disease. Conclusion : These data suggested that the ER22/23EK, N363S, and BclI SNPs in the NR3C1 gene do not affect the development of NS, initial steroid responsiveness, renal pathologic lesion, and progression to end-stage renal disease in Korean children with NS.

• Clinical and Experimental Pediatrics
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• v.50 no.11
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• pp.1116-1124
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• 2007

Purpose : Juvenile dermatomyositis (JDM) is the most common of the idiopathic inflammatory myopathies in children. The purpose of this study is to observe demographic, initial presentations, duration of time between disease onset and diagnosis, clinical manifestations and laboratory findings at diagnosis of patients with JDM. Methods : Forty seven patients identified at Seoul National University Children's Hospital from January 1986 to May 2007. Medical records were reviewed retrospectively focusing on initial presentations, clinical manifestations and laboratory findings at the time of diagnosis of patients with JDM. Results : Male and female patients were 25 and 22, respectively and sex ratio was 1.14:1. The average age at the time of diagnosis was 6.51 years. Skin rash (94%) was the most common symptom, followed by the proximal muscle weakness (89%). The disease activity score was 10.8. The duration between the onset of the skin rash and the muscle weakness and diagnosis was 7.18 and 4.70 months, respectively. The serum muscle enzymes, LDH, AST, CK and aldolase, were elevated in the patient with JDM. Autoimmune antibodies, antinuclear antibody, anti SSA antibody and anti SSB antibody, were negative findings. Electromyography findings were consistent with JDM in 88% of the patients, the muscle biopsy was in 91% and all MRI findings were compatible with those of patients with JDM. The most common symptom besides musculocutaneous lesions was the calcinosis (62.5%). The most common site of calcinosis was the pelvic area and buttocks. Conclusion : This study shows that the major symptoms are proximal muscle weakness and cutaneous lesion, and they are important to diagnose JDM.

• Journal of Veterinary Clinics
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• v.24 no.4
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• pp.503-508
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• 2007

Although canine facial nerve paralysis(FNP) occurs similarly in humans, there is no properly recognized therapy using Western medicine for idiopathic causes. To elucidate therapeutic measures by acupuncture(AP) on canine FNP, we examined the therapeutic effect of injection-AP on the artificially induced canine FNP. Twelve dogs on artificially induced canine FNP were divided into a control group(4 dogs), an experimental dexamethasone-treated group(dexamethasone group, 4 dogs) and an experimental bee venom-treated group(apitoxin group, 4 dogs). Saline (1 ml) was intramuscularly injected into the head muscle after the induction of FNP in the control group. On the other hand, injection-AP with dexamethasone was performed on such acupoints as LI04, LI20, ST02, ST07, TH17, SI18, GB03 and GB34, twice per week after induction of FNP in the dexamethasone group. In addition, injection-AP with $100{\mu}g$ of apitoxin was performed on the same acupoints as the dexamethasone group twice per week after the induction of FNP in the apitoxin group, respectively. The changes of the clinical symptoms of FNP with each treatment during the experimental period were recorded by using clinical scores, respectively. The changes of serum creatine kinase(CK) activities along with each treatment were determined using an autoanalyzer. The significant differences of clinical scores were detected on day 14(p<0.05) in the apitoxin and dexamethasone groups, compared with those in the control group, respectively. However, significant difference was not detected between the apitoxin and dexamethasone groups. Significant differences of serum CK activities were detected on day 7(p<0.05) and day 14(p<0.05) in the dexamethasone and apitoxin groups, compared with those in the control group, respectively. However, significant difference was not detected between the dexamethasone and apitoxin groups. In condition, injection-APs with apitoxin and dexamethasone were all effective for treatment of canine FNP and the therapeutic effect by injection-AP with apitoxin was similar to that of injection-AP with dexamethasone.

• Tuberculosis and Respiratory Diseases
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• v.51 no.3
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• pp.201-210
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• 2001

Background : Approximately 10-13% of patients with interstitial lung disease(ILD) die of lung cancer, and patients with ILD have been reported to have a 7 fold higher incidence of lung cancer compared to the normal population. Recently, overexpression of the p53 and p21 proteins were observed in the epithelial cells from pathologic specimens of ILD. Overexpression of these proteins may result from chronic or recurrent DNA damage by unknown causes of inflammation. However, these proteins may also contribute to oncogenesis if other genetic alterations such as K-ras are superimposed. Methods : Immunohistochemical stains for p53 and K-ras proteins were performed with pathologic specimens from 38 cases with ILD(M/F : 27/11, mean agea : $54{\pm}10$ years) and from 10 control subjects. Results : The p53 protein was expressed in 21.1% (8/38 ILD cases) and K-ras protein expression was observed in 65.8% (25/38 ILD cases). However, neither p53 nor the K-ras protein staining was observed in the control subjects. Conclusion : A significant proportion of cases with ILD expressed the p53 and K-ras proteins in their bronchial epithelial cells. These proteins may be potentially oncogenic with the addition of further genetic alterations. However, to clarify the significance of these findings, further studies looking for correlations with the incidence of lung cancer and other genetic changes are needed.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.13 no.1
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• pp.67-75
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• 2002

Objectives：This study was conducted to investigate the degree of psychopathologies of the family members of children with chronic convulsive disorder and evaluate the structures and dynamics of those families. Methods：The participant patients and family members were recruited from the population attending the outpatient clinic of department of pediatric neurology in Seoul National University Hospital in Korea. All the patients had idiopathic chronic convulsive disorder. Any patient with mental retardation, pervasive developmental disorder and gross brain pathology was excluded. As controls, normal students were chosen and their sex, age, achievement, socioeconomic status were matched to patients. The author interviewed the children and their family members twice and obtained informations about patient-parent relationship, patient-sibling relationship and others. For in-depth evaluation, we used family environment scales(FES), symptom Checklist-90-revised(SCL-90-R), self administered dependency questionnaire for mother(SADQ). Results：After interviewing with the parents of epileptic children, overprotection of parents, hostile feeling of siblings toward index children were higher than controls. The parental conflict was also more expressed than control families. According to results from FES, the scores of the subscales of expression, achievement-orientation, intelligence-orientation and active recreation were significantly lower than control group. The epileptic children showed higher dependency to parents especially in affection, communication and traveling areas of SADQ than control group. Maternal psychopathologies evaluated by SCL-90-R were much higher than the mothers of controls. According to T scores of SCL-90-R, about 40% of mothers with epileptic children had the risk of clinically significant depressive or anxiety disorders. Conclusion：These results suggested that the family members of epileptic children had more relationship problems and psychopathologies than control group and some mothers might have clinically significant depressive or anxiety disorders. so, effective psychiatric family interventions are needed for resolution of conflict and psychopathologies of family members.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.236-245
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• 2000

Background: Transbronchial lung biopsy(TBLB) has known to yield useful information for pulmonary infiltrates of uncertain etiology, However, its safety and usefulness have not been conclusive in the critically ill patients with respiratory failure. Moreover, TBLB has not been recommended for patients with mechanical ventilation. This study was conducted to investigate the diagnostic values and risks of Will performed on critically ill patients at bedside to obtain information on the pulmonary infiltrate of unknown etiology. Methods: Twenty patients(21 admissions with 23 cases) with diffuse pulmonary infiltrates who were treated in a medical intensive care unit of a tertiary referral hospital from January 1994 to May 1998, were enrolled for the study. Their medical records were retrospectively reviewed. TBLB was opted when a noninvasive diagnostic work-up failed to reveal the cause for the pulmonary infiltrate. The procedure was performed at patients' bedside without assistance of fluoroscopy. Bronchial washing or bronchoalveolar lavage was performed on the same pulmonary segment before performing TBLB. Results: Adequate specimens were obtained in 18 cases(78%). TBLB provided a specific diagnosis in two cases. The results of TBLB suggested the underlying etiology in 9 cases; bacterial pneumonitis(4), hypersensitivity pneumonitis(1), polymyositis(1), radiation fibrosis(1), idiopathic pulmonary fibrosis(1), and BOOP(1). Therapeutic decisions were altered in 11 cases(47.8%) based on the TBLB results. Pneumocystis carinii was found in the BAL fluid of another case. Ten patients with a therapeutic change and ten patients without a management change had mortality rates of 40% and 80%, respectively. The APACHE III scores were significantly higher in patients with complications($72.8{\pm}21.8$) compared with those without complications ($48.3{\pm}18.9$)(p<0.05). The complication rates were higher in those with mechanical ventilation(50%) than in those without Mechanical ventilation(33%), but the difference was not statistically significant(p=0.3). Conclusions: TBLB may be a useful diagnostic option for critically ill patients with unknown cause of pulmonary infiltrates. However, it should be cautious be used with care for patients with mechanical ventilation or for severely ill patients.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.547-557
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• 1996

Background : An excessive accumulation of neutrophils in lung tissue has been known to play an important role in mediating the tissue injury among the adult respiratory distress syndrome, idiopathic pulmonary fibrosis and cystic fibrosis by releasing toxic oxygen radicals and proteolytic enzymes. Therefore, it is important to understand a possible mechanism of neutrophil accumulation in lung tissue. In many species, exposure to hyperoxic stimuli can cause changes of lung tissues very similar to human adult respiratory distress syndrome and neutrophils are also functioning as the main effector cells in hyperoxic lung injury. The purpose of the present study was to examine whether neutrophils function as a key effector cell and to study the nature of possible neutrophil chemotactic factors found in bronchoalveolar lavage fluid from the hyperoxia exposed rats. Methods : We exposed the rats to the more than 95% oxygen for 24, 48, 60 arid 72 hours and bronchoalveolar lavage(BAL) was performed. Neutrophil chemotactic activity was measured from the BAT- fluid of each experimental groups. We also evaluated the molecular weight of neutrophil chemotactic tractors using fast performance liquid chromatography and characterized the substances by dialyzer membrane and heat treatment. Results : 1) The neutrophil proportions in bronchoalveolar lavage fluid began to rise from 48 hours after oxygen exposure, and continued to be significantly increased with exposure times. 2) chemotactic index for neutrophils in lung lavages from rats exposed to hyperoxia was significantly higher in 48 hours group than in control group, and was significantly increased with exposure time. 3) No deaths occured until after 48 hours of exposure. However, mortality rates were increased to 33.3 % in 60 hours group and 81.3 % in 72 fours group. 4) Gel filtration using fast performance liquid chromatography disclosed two peaks of neutrophil chemotactic activity in molecular weight of 104,000 and 12,000 daltons. 5) Chemotactic indices of bronchoalveolar lavage fluid were significantly deceased when bronchoalveolar lavage fluid was treated with heat ($56^{\circ}C$ for 30 min or $100^{\circ}C$ for 10 min) or dialyzed (dialyzer membrane molecular weight cut off : 12,000 daltons). Conclusion : These results suggested that the generation of neutrophil chemotactic factor and subsequent neutrophil influx into the lungs are playing an important roles in hyperoxia-induced acute lung injury. Neutrophil chemotactic factor in the lung lavage fluids consisted of several distinct components having different molecular weight and different physical characteristics.

• Neonatal Medicine
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• v.18 no.2
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• pp.221-227
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• 2011

Purpose: The objectives were to identify the characteristics of neonates with hydrops fetalis, and to identify the risk factors associated with mortality. Methods: A retrospective review of AMC (Asan Medical Center) dataset was performed from January 1990 to June 2009. The characteristics of 71 patients with hydrops fetalis were investigated and they were divided into two groups: the survived group and the expired group. Various perinatal and neonatal factors in two groups were compared to find out risk factors associated with mortality based on univariate analysis, followed by multiple regression analyses (SPSS version 18.0). Results: Of those 71 neonates (average gestational age: 33 weeks, birth weight: 2.6 kg), 38 survived, 33 died, resulting in overall mortality rate of 46.5%. The most common etiology was idiopathic followed by chylothorax, cardiac anomalies, twin-to-twin transfusion, meconium peritonitis, cardiac arrythmias, and congenital infections. Factors that were associated independently with mortality in logistic regression analyses were low 5-minutes Apgar score, hyaline membrane disease and delayed in achieving 50th percentile ideal body weight for appropriate gestational age by 10 days. Conclusion: In this study, 5-minutes Apgar score, hyaline membrane disease and delayed in achieving 50th percentile ideal body weight for appropriate gestational age by 10 days were significant risk factors associated with mortality in hydrops fetalis. Therefore, the risk of death among neonates with hydrops fetalis depends on the illness immediately after birth and severity of hydrops fetalis. Informations from this study may prove useful in prediction of prognosis to neonates with hydrops fetalis.

• Clinical and Experimental Pediatrics
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• v.49 no.6
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• pp.659-664
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• 2006

Purpose : To evaluate the morbidity and mortality of children with status epilepticus(SE) as an initial seizure and to compare these according to age groups. Methods : The 78 cases(38 cases <2 years and 38 cases ${\geq}2$ years) with SE as an initial seizure admitted to the Chonnam national university hospital from Jan. 2000 to Jan. 2004 were reviewed. Developmental profiles, laboratory findings, etiologies and seizure types of SE and outcomes were compared in between two age groups, under and over 2 years. Results : SE occurred predominantly in less than 5 years old. Febrile causes were the most common, which is significantly more in those under 2 years than over 2 years(P<0.05). whereas idiopathic and acute symptomatic causes were more common in those over 2 years(P<0.05). Generalized tonic-clonic seizures was the most common type. The mortality rate was 6.4 percent(5 cases : 1 case <2 years and 4 cases ${\geq}2$ years). The estimated occurrence of epilepsy after SE was 24.4 percent(19 cases : 8 cases <2 years and 11 cases ${\geq}2$ years). The neurologic sequelae after SE in cases that had developed normally before SE(62 cases : 32 cases <2 years and 30 cases ${\geq}2$ years) were observed in 20 cases(32.3 percent), and were more frequent over 2 years(21.9 percent vs. 43.3 percent, P<0.05). Conclusion : In this study death was less common and the neurologic sequelaes of SE as an initial seizure were less severe in children under 2 years of age. The reason seemed to be the difference in the etiology of SE with age.