Purpose : Fragile sites are points on chromosomes which tend to break non-randomly when exposed to specific chemical agents or conditions of tissue culture. The chromosomal break induced by the antineoplastic drug, 1-${\beta}$-D-arabinofuranosyl-cytosine(Ara-c), was investigated to study the laboratory conditions in which the incidence of chromosomal break could be enhanced. Besides, the fragile sites induced by Ara-C were investigated and compared to the already known locations of the specific chromosomal alterations observed in specific neoplasms. Methods : T-lymphocytes from theree normal males and three females were cultured for 48 hours. Cells from each individual were exposed to the Ara-C for an additional 24 hours. After the caffeine was added during the last six hours culture, the metaphase chromosomes were prepared following the conventional method. A site was considered fragile if it was found to break two or more per 100 chromosomal breaks in more than four of six individuals tested. Results : Ara-C induced 252.1 chromosomal breaks per 100 mitotic cells and this result was significantly higher than that of the control, which induced 25.2 breaks(P<0.05). The incidence of the chromosomal break by Ara-C was higher, if cultured in the MEM-FA, which has no folic acid, than in the RPMI 1640 which contains enough folic acid(P<0.05). The most common break site by Ara-C was 3p14.2(FRA3B). There were 20 fragile sites induced by Ara-C. Among these 20 fragile sites, seven coincided with the locations of the mapped oncogenes, JUN, SKI, REL, N-MYC, FHIT, MET, ETS-1, and FOS. Conclusion : S phase specific chemotherapeutic agent, Ara-C, induced the expression of the chromosomal fragile sites effectively using the T-lymphocyte in vitro. Some of the fragile sites by Ara-C highly coincided with the oncogenes and neoplasm specific chromosome breakpoints. In this regard, the fragile sites reported here could provide the unknown neoplasm related chromosomal alternation points.
Shin, Hye Kyoung;Kim, Ji Hee;Yoo, Kee Hwan;Hong, Young Sook;Lee, Joo Won;Kim, Soon Kyum
Clinical and Experimental Pediatrics
/
v.46
no.9
/
pp.889-892
/
2003
Purpose : This study aimed to evaluate risk factors of the first year relapse in children with nephrotic syndrome(NS) without the need for biopsy. Methods : We reviewed, retrospectively, 78 children diagnosed with steroid responsive nephrotic syndrome between July 1997 and June 2002. Median years to follow up were 4.4 years(range : 1-5 years). We divided the patients into two groups(group I : primary responders with no relapse or with only two relapses in the first year after initial response; group II : initial steroid responders with three or more relapses within the first year). We retrospectively reviewed and compared variables - sex, onset age, serum albumin, serum cholesterol, 24 hours urinary protein, creatinine clearance(Ccr), presence of hematuria and hypertension(HTN), and days from initial attack to remission. Results : Of 78 patients(male : 61(78.2%), female : 17(21.8%), age range 1.1 years to 14 years, median $5.1{\pm}3.0years$), 47(60.3%) were in group I and 31(39.7%) were in group II. There were no statistically significant differences in sex, serum albumin, serum cholesterol, 24 hours urinary protein, Ccr, presence of hematuria or HTN. The median age of onset showed no statistical difference between the two groups. However, if the patients are dividing into two groups according to the age of onset of three-years, patients theree yrs old or less fit into group II, as opposed to patients older than three yrs in age(63.2% vs. 32.2%, P<0.05). The days from initial attack to remission was longer in group II($12.9{\pm}0.5$ vs. $16.2{\pm}1.1$, P<0.05). Conclusion : We may conclude that the age of onset of three yrs old or less, and the longer time remission to initial steroid therapy, are risk factors of the first year relapse.
Purpose : Craniopharyngiomas are often accompanied by severe endocrine disorders. Although there is universal growth hormone deficiency(GHD), the resulting growth pattern is very heterogeneous. We report the growth and endocrine outcome of 44 children with craniopharyngioma, with emphasis on initial symptoms, growth before and during growth hormone(GH) treatment and spontaneous growth in spite of GHD. Methods : We performed a retrospective study of 44 children treated at our centre between 1984 and 2002. Results : About 30% of patients had symptoms suggesting endocrine disorder at diagnosis. After surgery, multiple endocrinopathies were almost universal. Before GH therapy, height velocity was $8.00{\pm}2.71cm/yr$ in the normal growth group(n=11) and $1.79{\pm}1.10cm/yr$ in the subnormal growth group(n=7) during the first year and during the second year, $6.76{\pm}2.49cm/yr$ and $2.29{\pm}1.33cm/yr$, respectively. There was no difference of body mass index(BMI) change between before and after surgery in the two groups. Height standard deviation score(SDS) was $-1.46{\pm}0.74$ in the normal growth group and $-0.43{\pm}0.97$ in the subnormal growth group. Before GH treatment height SDS was $-1.31{\pm}1.25$ and BMI was $20.46{\pm}3.60$. During GH treatment, height SDS increased to $-0.60{\pm}1.37$ in the first, and to $-0.41{\pm}1.54$ in the second year(P<0.05), but BMI did not change significantly. Conclusion : The endocrine morbidity could develop in most children with craniopharyngioma before and after the operation and should be managed properly. Although all treated patients benefit from GH therapy, further studies are necessary to find out the possible mechanism of growth regulation in normally growing children, despite GH deficient.
Nah, Kyu Min;Park, Yang;Kang, Eun Kyeong;Kang, Hee;Koh, Young Yull;Lee, Sun Wha;Paek, Domyung
Clinical and Experimental Pediatrics
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v.46
no.3
/
pp.284-290
/
2003
Purpose : A new airway inflammatory marker, exhaled nitric oxide(ENO) has been reported to correlate with bronchial hyperresponsiveness(BHR) and atopy. The purpose of this study was to analyze the relationship of ENO with BHR or atopy in patients with asthma and with allergic rhinitis. Methods : The subjects consisted of 55 children with asthma, 17 with allergic rhinitis, and 14 healthy controls. The asthma group was subdivided into the atopic asthma group(n=37) and the nonatopic asthma group(n=18) and the allergic rhinitis group into BHR group(n=7) and non-BHR group(n=10). All were investigated with spirometry and measurements of ENO concentration. The correlations between ENO concentration and both methacholine $PC_{20}$(provocative concentration causing a 20% decrease in forced expiratory volume in one second) and the number of allergen skin test positivity were analyzed. Results : ENO concentrations of both asthma and allergic rhinitis groups were significantly greater than that of control(P<0.01). ENO concentration of atopic asthma was significantly greater than that of nonatopic asthma(P<0.01). In allergic rhinitis, ENO concentration did not differ according to the presence or absence of BHR(P=0.50). ENO concentrations correlated significantly with the number of skin test positivity(r=0.32, P=0.02) or methacholine $PC_{20}$(r=-0.38, P<0.01) in asthma group, but not in the allergic rhinitis group(r=0.42, P=0.09; r=-0.06, P=0.83). Conclusion : In asthma patients, some pathogenetic mechanisms associated with atopy and BHR seem to influence ENO concentration. In allergic rhinitis patients, some factors other than BHR may be important in determining ENO concentration.
Kang, Eun Kyeong;Na, Kyu Min;Kang, Hee;Yoo, Young;Koh, Young Yull
Clinical and Experimental Pediatrics
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v.46
no.4
/
pp.370-375
/
2003
Purpose : It has been suggested that the exposure to aeroallergens during early infancy after birth is important in the subsequent development of sensitization and allergic diseases. In Korea, the level of house dust mites as one of the important aeroallergens is known to be the highest in autumn. The aim of this study was to test whether the distribution of month of birth bears a relationship to the presence of mite sensitization in children with respiratory allergy. Methods : Skin prick tests and methacholine provocation tests were performed on 1,327 patients with chronic respiratory symptoms who visited Seoul National University Children's Hospital from January 1995 to May 2002. An analysis of patients' month of birth distribution according to the presence of mite sensitization was performed. Results : Atopic subjects who had at least one positive skin test numbered 864(65.1%); and non-atopic subjects numbered 463(34.9%). Among atopic subjects, 787(59.3%) had positive skin tests to mites and 77(5.8%) had positive skin test only to minor allergens. A significantly greater than expected number of mite atopic subjects were born in the months between August and November(P=0.03), however, the birth month of non-atopic subjects didn't show a consistent seasonal preference. Asthma patients numbered 543(40.9%). Among these, atopic asthmatics numbered 421(77.5%) and non-atopic asthmatics, 122(22.5%). Dust-mite atopic asthmatics numbered 387(91.9%) out of 421 atopic asthmatics. Dust-mite atopic asthmatics were born significantly higher in the season lasting from August to November in comparison to non-atopic asthmatics(P=0.002). Conclusion : Month of birth seems to be related with sensitization to allergens. Our results show that August to November is the risk period for the development of mite sensitization in Korea.
Choi, Deok Young;Choi, Jae Young;Kim, Mi Jin;Sul, Jun Hee;Lee, Sung Kyu
Clinical and Experimental Pediatrics
/
v.46
no.9
/
pp.871-875
/
2003
Purpose : This study was performed to follow the natural course and size change of isolated atrial septal defect(ASD) secundum. Methods : Among the newly diagnosed with ASD secundum at the division of pediatric cardiology in Yonsei cardiovascular hospital from January 1996 to December 2000, 89 patients with pure ASD secundum were checked by the serial echocardiographic evaluation to measure the size change. Results : There was a statistical difference(P<0.05) in the rate of spontaneous closure and size change of the defect between the group of bigger defect(>8 mm) and the group of smaller defect (${\leq}8mm$). There was also a statistical difference(P<0.05) in the rate of spontaneous closure and size change of the defect between the group of younger than three years of age and the group of older than three years of age. The initial size of the defect and change of size were the significant influencing factors in the rate of spontaneous closing of ASD. In the group of patients who have persistent ASD, the size of defect showed a tendency of increasing size of defect with the age(P<0.005); however in the correction of these values by the body surface area of each patients, there was no statistical difference. Conclusion : The possibility of spontaneous closure of pure ASD secundum was higher in the group of patients who have smaller defect and who were younger. The ASD secundum that did not have spontaneous closure showed an increase in size with the growth of the patients; however when this size was corrected by the body surface area, there was no statistical difference. The closure of the defect was at 26.2 months of age so close follow-up of the patients is important.
Cheong, Hee Jeong;Kim, Hye Rim;Lee, Seong Soo;Bae, Eun Joo;Park, Won Il;Lee, Hong Jin;Choi, Hui Chul
Clinical and Experimental Pediatrics
/
v.52
no.2
/
pp.199-204
/
2009
Purpose : Seizure associated with fever may indicate the presence of underlying inherited metabolic diseases. The present study was performed to investigate the presence of underlying metabolic diseases in patients with complex febrile seizures, using analyses of urine organic acids. Method : We retrospectively analyzed and compared the results of urine organic acid analysis with routine laboratory findings in 278 patients referred for complex febrile seizure. Results : Of 278 patients, 132 had no abnormal laboratory findings, and 146 patients had at least one of the following abnormal laboratory findings: acidosis (n=58), hyperammonemia (n=55), hypoglycemia (n=21), ketosis (n=12). Twenty-six (19.7 %) of the 132 patients with no abnormal findings and 104 (71.2%) of the 146 patients with statistically significant abnormalities showed abnormalities on the organic acid analysis (P<0.05). Mitochondrial respiratory chain disorders (n=23) were the most common diseases found in the normal routine laboratory group, followed by PDH deficiency (n=2) and ketolytic defect (n=1). In the abnormal routine laboratory group, mitochondrial respiratory chain disorder (n=29) was the most common disease, followed by ketolytic defects (n=27), PDH deficiency (n=9), glutaric aciduria type II (n=9), 3-methylglutaconic aciduria type III (n=6), biotinidase deficiency (n=5), propionic acidemia (n=4), methylmalonic acidemia (n=2), 3-hydroxyisobutyric aciduria (n=2), orotic aciduria (n=2), fatty acid oxidation disorders (n=2), 2-methylbranched chain acyl CoA dehydrogenase deficiency (n=2), 3-methylglutaconic aciduria type I (n=1), maple syrup urine disease (n=1), isovaleric acidemia (n=1), HMG-CoA lyase deficiency (n=1), L-2-hydroxyglutaric aciduria (n=1), and pyruvate carboxylase deficiency (n=1). Conclusion : These findings suggest that urine organic acid analysis should be performed in all patients with complex febrile seizure and other risk factors for early detection of inherited metabolic diseases.
Kim, Jae Kwang;Jin, Hyun Seong;Han, Myung Ki;Kim, Bong Seong;Cha, Choong Hwan;Park, Kie Young
Clinical and Experimental Pediatrics
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v.52
no.2
/
pp.167-175
/
2009
Purpose : This study has been conducted to analyze whether the biochemical nutrition indexes might be useful and effective for evaluating the nutrition states of children. Methods : We evaluated 269 children, aged 3-9 years old, who had visited Gangneung Asan Hospital for elective surgery from January 2006 to December 2007, and examined their anthropometric and preoperative laboratory data with retrospective analysis. The children were classified into underweight, normal weight, overweight, and obese groups according to body mass index (BMI). The biochemical nutrition indexes (total lymphocyte count (TLC), hemoglobin, hematocrit, serum albumin, cholesterol, et al) of each group were then analyzed statistically. Results : None of the groups showed statistically significant differences in TLC. Serum albumin decreased significantly in the underweight group. Red blood cell (RBC) count, hemoglobin, hematocrit, and serum total cholesterol in the obese group were higher than in the normal weight group. None of the groups showed statistically significant increase in mean corpuscular volume or mean corpuscular hemoglobin, and it seems that the increase of hemoglobin and RBC count in the overweight and obese groups is due to the enhancement of erythropoiesis rather than iron metabolism. However, in females, almost all nutrition indexes except albumin were statistically significantly poor. Conclusion : Serum albumin, total cholesterol, RBC count, hemoglobin, and hematocrit were useful as nutrition indexes. However, except for albumin, these indexes were significantly poor for females. More control studies are needed to confirm the effectiveness of biochemical indexes for evaluating the nutritional state of children.
Lee, Young Ah;Chung, Hye Rim;Lee, Se Min;Kim, Jae Hyun;Kim, Ji Hyun;Lee, Sun Hee;Shin, Choong Ho;Yang, Sei Won
Clinical and Experimental Pediatrics
/
v.52
no.2
/
pp.227-233
/
2009
Purpose : Growth hormone (GH) replacement after retesting is necessary because impairment of body composition and cardiovascular health has been more severe in adult patients with persistent GH deficiency (GHD) from childhood to adulthood. This study aimed to investigate the factors for persistent GHD and define a highly probable group of persistent GHD in young adults with childhood-onset GHD. Methods : GHD was reassessed by insulin tolerance test (ITT) in 55 adult patients (39 males, 16 females) with childhood-onset GHD. Twelve patients presented with idiopathic GHD and 43 patients presented with organic GHD caused by tumors involving the hypothalamus-pituitary (H-P) region (n=33), other brain tumors (n=3), meningitis (n=3), leukemia (n=2) and others (n=2). Results : Forty-nine (89.1%) of 55 patients had persistent GHD. IGF-I was positively correlated with log of peak GH (r=0.57, P<0.001). There was no difference in the proportion of persistent GHD between idiopathic and organic GHD. The percentage of patients with persistent GHD was 40%, 80%, and 95.6% for patients with zero, one, two or more additional pituitary hormone deficiencies (PHDs), respectively (P=0.002). The probability of persistent GHD was higher in patients with diseases involving the H-P region (P=0.003). GHD persisted in 15 of 18 patients treated with cranial irradiation. Conclusion : We suggest that the probability of persistent GHD in adulthood was high in patients with 2 or more additional PHDs, and diseases involving the H-P region.
Kim, Tai Sung;Hur, Tae Hyung;Lim, Sun Jeong;Bin, Joong Hyun;Hahn, Seung Hoon;Kim, So Young;Kim, Hyun Hee;Lee, Wonbae
Clinical and Experimental Pediatrics
/
v.51
no.4
/
pp.396-400
/
2008
Purpose : The study was performed to assess the distribution of the diseases associated with nonspecific reactive hepatitis (NRH) for the past 10 years and to evaluate the change in the level of AST and ALT, and the difference by several variable factors. Methods : From January 1997 to December 2006, 646 patients had elevated liver enzymes among 22,763 patients admitted to the Holy Family Hospital. We analyzed the difference in the age distribution, the period of elevated levels of AST and ALT, the resolution period, the peak value, the daily resolution value of AST and ALT, the sexual differences and the difference in several disease entities. One hundred and ninety-seven patients not confirmed as NRH or lost during follow-up were excluded. Results : The prevalence rate of NRH was 2.84%. When compared to AST, ALT showed longer period of morbidity and resolution and the peak value was also higher in ALT. The male and female ratio showed significant value of 1.63:1. The morbid and resolution periods of AST and ALT between males and females were longer periods in males. The most prevalent disease entities were respiratory and gastrointestinal infections. Between the respiratory and the gastrointestinal diseases, the highest level of AST and ALT was observed in the respiratory disease. Conclusion : NRH is a common disease that occurs in 2.84% of the admitted pediatric patients. However, the pathogenesis and the progress of the disease have not been well known due to the lack of generalized information. Further research is necessary in the future.
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