• Clinical and Experimental Pediatrics
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• v.49 no.6
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• pp.610-616
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• 2006

Purpose : The purpose of this study was to evaluate the timing of sexual maturation and secular trends of menarchial age in Korean adolescents. Methods : Nine hundred eighty two school students and 119 university female students were included. Tanner's pubertal assessment method was applied using a self-assessment sheet with pictures for their developmental stages. A medical checkup database from 1,156,022 women was also used to analyze the age of menarche from the year 1900 to 1980. Results : Onset of puberty was at $11.3{\pm}1.3$ years(y) in girls and $12.1{\pm}1.5$ y in boys and total pubertal duration was 3.6 y in girls and 3.3 y in boys. Height at the onset of puberty was $146.1{\pm}7.9cm$ in girls and $152.7{\pm}9.8cm$ in boys. Weight at the onset of puberty was $39.3{\pm}6.9kg$ in girls and $47.7{\pm}14.4kg$ in boys. The mean age of menarche was $12.0{\pm}1.0y$ and mean age at nocturnal emission was $12.3{\pm}1.8y$. By age ten, 3.0 percent of girls experienced menarche, which increased to 41.1 percent by age 12, and 98.0 percent by age over 15. By SMR 2 breast stage, 18.2 percent of girls experienced menarche, which increased to 66.1 percent and 91.7 percent by SMR stages 3 and 4, respectively. By SMR 2 pubic hair stage, 52.0 percent and by SMR 3, 93.8 percent of girls experienced menarche. While the menarchial age of women born around 1980 was $12.4{\pm}1.1y$, the menarchial age of women born around 1990 was $12.0{\pm}1.1y$. Age at menarche has been advanced approximately by 2 years between 1900 and 1980 birth cohorts. Conclusion : There was a downward secular trend in pubertal timing. Age at menarche has been advanced by 2 years during the last 80 years. Further large scale, prospective studies, including inspection by specialists, are needed to provide reference data for pubertal timing in Korean adolescents.

• Clinical and Experimental Pediatrics
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• v.52 no.12
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• pp.1377-1382
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• 2009

Purpose:The gonadotropin-releasing hormone (GnRH) test results of girls with precocious puberty were analyzed to determine whether this test can efficiently and clearly differentiate between central precocious puberty (CPP) and other disorders. Methods:Clinical and laboratory data of 54 girls with precocious pubertal signs were reviewed. Intravenous GnRH test was performed with blood samples obtained at 0, 30, 60, and 90 minutes. A peak luteinizing hormone (LH) level of ${\geq}5.0IU/L$ was indicative of CPP. Results:Of the 40 girls with CPP, 36 (90.0%), 3 (7.5%), and 1 (2.5%) showed peak LH levels at 30, 60, and 90 minutes, respectively. A percentage of girls whose peak LH ${\geq}5.0IU/L$ up to 30, 60, and 90 minutes was 92.5%, 100%, and 100%, respectively. The peak LH/follicle stimulating hormone (FSH) ratio of girls with CPP was 0.89${\pm}$0.49 and was <1 in 16 of the 40 girls (40.0%). Girls with peak LH/FSH ratio of >1.0 showed higher chronological age (CA) ($8.3{\pm}0.6$ vs. $7.7{\pm}1.0$ years, P=0.033), bone age (BA) ($10.9{\pm}0.8$ vs. $9.7{\pm}1.1$ years, P=0.001), and BA-CA difference ($2.6{\pm}0.7$ vs. $2.0{\pm}0.7$ years, P=0.009) than those of girls with peak LH/FSH ratio of ${\leq}1.0$. Higher percentage of girls with peak LH/FSH ratio of >1.0 showed advanced breast development (${\geq}TannerIII$) (93.7% vs. 41.7%, P=0.001). Conclusion:LH levels after 30 and 60 minutes of intravenous GnRH administration are the most useful for diagnosing CPP in girls.

• Clinical and Experimental Pediatrics
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• v.50 no.12
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• pp.1188-1193
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• 2007

Purpose : The prevalence of rickets in the world is on the rise not only in developing but also in developed countries. In Korea, breastfeeding has increased. There have been few studies on the possible association of rickets with breastfeeding. The purpose of this study was to identify the development and the clinical presentation of subclinical rickets in breastfed infants. Methods : We investigated patients who were breastfed and had hypovitaminosis D in the blood from May 2006 to April 2007, and who were diagnosed with vitamin D deficient rickets from May 2003 to April 2006. We evaluated the results of blood tests, x-rays and other relevant information in the medical record. A questionnaire that included questions on the diet of patients, the mothers activity during pregnancy and place of residence was administered. Results : Twelve patients (66%: male, 34%: female) were enrolled in this study. There were eight in the asymptomatic and four in the symptomatic group. The median age for each group was 8 months (range 4-11 month) and 5.5 months (5-8 month). All patients in the symptomatic group were breastfed until diagnosed. In the asymptomatic group, they were breastfed for four to six months, and then weaned with only thin rice soup and vegetables. Nine patients had a vitamin D concentration below 20 ng/mL and three patients had levels between 20 and 29 ng/mL. Alkaline phosphatase (ALP) and parathyroid hormone (PTH) were elevated in both groups. There were statistically significant $25-OHD_3$ levels in the blood in both groups (P=0.008). Ten of the patients (83%) also had iron deficient anemia. Conclusion : Vitamin D deficiency and subclinical rickets has been identified in Korea. However, the prevalence of this disease has not been determined. The main limitation of this study was the small number of patients and the absence of a control group.

• Clinical and Experimental Pediatrics
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• v.51 no.7
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• pp.704-712
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• 2008

Purpose : A prospective, controlled trial was conducted to evaluate growth, efficacy, safety and nutritional status for very low birth weight infants fed with human milk fortified with Maeil human milk fortifier (Maeil $HMF^{(R)}$; Maeil Dairies Co., Ltd.). Methods : We enrolled 45 premature infants with a birth weight <1,500 g and gestational age <33 weeks, who were born at Dong-A University Hospital from October, 2006 through December, 2007. They were divided into 2 groups: infants in one group were fed with human milk fortified with $HMF^{(R)}$, and the second were fed with preterm formula. Growth, biochemical indices, feeding tolerance, and other adverse events in each group were assessed serially and compared relatively. Follow-up data were also collected after discharge at 1, 3, and 6 months corrected age. Results : Characteristics of the 2 groups including average gestational age, birth weight, sex, respiratory distress syndrome, patent ductus arteriosus, and other adverse events (sepsis, retinopathy of prematurity, and intraventricular hemorrhage) showed no significant difference. Average feeding start day ($8.00{\pm}3.27d$ vs. $8.86{\pm}5.37d$) (P=0.99) and the number of days required to reach full feeding after start feeding ($41.78{\pm}20.47d$ vs $36.86{\pm}20.63d$) (P=0.55) were not significantly different in the group fed human milk fortified with $HMF^{(R)}$ when compared with the group that was fed preterm formula. The duration of total parenteral nutrition and the incidence of feeding intolerance also showed no differences between the 2 groups. Although infants fed with human milk fortified with $HMF^{(R)}$ showed faster weight gain than those fed with preterm formula at the end stage of the admission period, other growth indices of the two groups showed no significant difference. No significant correlations were found between the 2 groups with regard to weight gain velocity, height gain velocity, head circumference velocity, and post-discharge follow up growth indices. Conclusion : Premature infants fed human milk fortified with $HMF^{(R)}$ showed no significant difference compared with those fed preterm formula in growth, biochemical indices, and adverse events. Using human milk fortifier can be an alternative choice for very low birth weight infants, who need high levels nutritional support even after discharge from NICU.

• Clinical and Experimental Pediatrics
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• v.48 no.9
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• pp.991-997
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• 2005

Purpose : Cow's milk protein-induced enterocolitis(CMPIE) is a symptom complex of vomiting and/or diarrhea caused by delayed hypersensitivity and may result in serious complications. This study was undertaken to identify high risk factors to facilitate the early recognition of CMPIE. Methods : We reviewed the data of 101 patients, aged 15 to 45 days, admitted due to vomiting and/or diarrhea between 2003 and 2004. After excluding 13 patients absolutely breast-fed and 2 patients transferred from other hospitals with the impression of CMPIE, the 86 study subjects were divided into three groups based on the underlying etiologies; CMPIE, infectious and non-infectious group. Results : CMPIE was diagnosed in 11 patients(12.8%). On admission, failure to gain weight(P=0.003), hypoalbuminemia(P=0.003), peripheral leukocytosis(P=0.015), and metabolic acidosis(P=0.014) were more significant in the CMPIE group than in the others. Multiple logistic regression analysis showed that the independent predictors of high risks for CMPIE were failure to gain weight <10 g/day(OR, 10.25[95% CI, 1.62-65.06]) and serum hypoalbuminemia <3.5 g/dL(OR, 9.18[95% CI, 1.69-49.74]). Cow's milk challenges were performed in the 11 CMPIE patients; vomiting(81.8%), abnormal stool test(80.0%), peripheral leukocyte count and absolute neutrophil count(ANC) increase(100.0%) (P<0.05), and enteropathy(100.0%). Conclusion : CMPIE is not a rare clinical disease in early infancy. The high risk factors of CMPIE were identified as follow : failure to gain weight below 10 g/day, hypoalbuminemia on admission and a rapid decrease during admission. Cow's milk challenge test with endoscopic duodenal biopsy was helpful to confirm CMPIE.

• Clinical and Experimental Pediatrics
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• v.48 no.9
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• pp.986-990
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• 2005

Purpose : Certain strains of lactobacilli are known to accelerate recovery from acute diarrhea. Lactobacillus reuteri is isolated from human breast milk and a commonly occurring Lactobacillus species with therapeutic potential in acute diarrhea. The purpose of the present study was to investigate the therapeutic effect of L. reuteri in acute diarrhea in young children. Methods : Fifty patients between 6 and 36 months of age hospitalized with acute diarrhea (rotavirus in 40 percent) were randomized into two groups to receive either $10^8$ colony-forming units of L. reuteri or a matching placebo, twice a day for their length of hospitalization, or for up to 5 days. Antidiarrheal drugs were not prescribed to either group. The clinical outcome of diarrhea was evaluated. Results : The mean duration of watery diarrhea after initiation of treatment was 2.3 days for the L. leuteri group(n=25) vs. 2.9 days for the placebo group(n=25)(P=0.072). By the second day of treatment, watery diarrhea persisted in 64 percent of patients receiving L. reuteri, compared to 84 percent of those receiving placebo(P=0.006). On the second day, the mean frequency of watery diarrhea was 1.9 in the L. leuteri group and 3.4 in the placebo(P=0.046). Also, vomiting continued to the second day in 16 percent of patients receiving L. reuteri and 40 percent of those recieving placebo(P=0.031). Conclusion : L. reuteri is effective as a therapeutic agent in acute diarrhea in children.

• Clinical and Experimental Pediatrics
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• v.49 no.4
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• pp.431-438
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• 2006

Purpose : Insulin-like growth factor binding protein(IGFBP)-3 has been known as a tumor suppressor gene, and its anti-tumor function was divided into insulin-like growth factor(IGF)-dependent and IGF-independent mechanism. In IGF-independent mechanism, IGFBP-3 directly interacts with a cell without binding of IGFs, becoming an interesting object in oncology. Several studies demonstrate that one of the well-known tumor suppressor genes, p53, induces directly IGFBP-3 transcription, and the increment of IGFBP-3 expression induces apoptosis of many cancer cells. Recently, the anti-tumor mechanisms of IGFBP-3 have been reported, but post-translational modification of IGFBP-3 and its anti-tumor mechanism are not well known. In this study, we examined whether p53 regulated the glycosylation of IGFBP-3, and analysed the meaning of IGFBP-3 glycosylation related to the apoptosis of cancer cell. Methods : The p53-mutated status of MDA-MB-231 human breast cancer cells was used in this experiment. The expression and glycosylation of IGFBP-3 were tested by Western blot analysis after infection of adenovirus mediated Ad/p53 and/or Ad/IGFBP-3. Results : Ad/p53 infected cells resulted in growth retardation and the induced apoptosis. p53 induced direct expression and glycosylation of IGFBP-3. The increase of glcosylated IGFBP-3 was able to promote cellular apoptosis, and the glycosylation of IGFBP-3 was more activated by the double treatment of Ad/p53 and Ad/IGFBP-3. Conclusion : From this study, the anti-tumor activity of IGFBP-3 was shown to improve the stabilization of IGFBP-3 through the increment of glycosylation of IGFBP-3 by p53. This result suggests that the combined gene therapy of p53 and IGFBP-3 may appropriate treatment of cancer.

• Clinical and Experimental Pediatrics
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• v.48 no.10
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• pp.1121-1125
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• 2005

Purpose : Rotavirus is the main cause of infantile diarrheal disease worldwide, especially in patients 3-24 months of age. Infants younger than 3 months of age are relatively protected by transplacental antibody. So the purpose of this study is to evaluate the clinical features and severity of neonatal rotaviral gastroenteritis less than 1 month of age. Methods : A retrospective chart review was established of 62 neonates less than 1 month of age and with a diagnosis of rotaviral gastroenteritis who had been admitted to Pochon CHA University between June 2002 through July 2004. The rotavirus was examined by stool latex agglutination. Results : During 2 years, the total number of admitted patients for rotaviral gastroenteritis was 688 and among these, less than 1 month of age accounted for 9%(62). The occurrence was generally even distribution from January to July($7.14{\pm}1.0$) but since then decreased($2.4{\pm}1.8$). The most common chief complaint was mild fever(46%) when admitted which subsided within 1 hospital day in most patients. 4 patients had seizure and cyanosis with no typical symptoms of rotaviral gastroenteritis. During admission, all the patients had diarrhea. 17% of the patients had leukocytosis and positive C-reactive protein. In one patient, stool occult blood test was positive but there was no necrotizing gastroenteritis evidence. The mean period of hospital day was $5.8{\pm}2.5$ and breast-milk feeding was 62.9%. Conclusion : Neonatal rotaviral gastroenteritis is not a rare disease. Most patients have fever and diarrhea and improve through conservative therapy but a few patients may have severe complications so we must be more cautious about the hygiene for prevention.

• Clinical and Experimental Pediatrics
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• v.51 no.5
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• pp.468-473
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• 2008

Purpose : Iron-deficiency anemia (IDA) is still one of the most common nutrient deficiency disorders, despite improvements in general health and nutrition. This study was designed to investigate the diagnostic values of hematological profiles, including the level of ferritin, and to evaluate the knowledge of mothers on weaning practices for infants and young children with IDA. Methods : This study was conducted on 111 infants and young children from six to 40 months of age with IDA. Their parents completed a questionnaire. IDA was defined as a level of hemoglobin <11.0 g/dL, the presence of microcytosis, a level of ferritin <10.0 ng/dL, transferrin saturation <15%, or an 1 g/dL increase in the level of hemoglobin after iron administration. The questionnaire made inquiries into their weaning practices. Results : In 111 infants and young children aged from six to 40 months, the average level of Hb was $9.5{\pm}1.0g/dL$. The prevalence of ferritin level (>10 ng/dL) was 48.6%, in spite of IDA. Seventy-four infants (66.7%) began to wean between four and six months, and 37 infants (33.3%) after seven months of age. The main food given after weaning was rice gruel. The weaning periods showed a significant relationship to the severity of anemia (P<0.05). There was no significant difference in the severity of anemia in terms of the educational levels of the mothers. Fifty-five mothers (49.5%) gave a wrong answer to a questionnaire describing that breast-fed infants aged over four months need to be fed with iron-sufficient food. Of all mothers, 49.6% took one month or more to complete the weaning process and 20% took three months or more. Conclusion : Many infants and young children with IDA have been provided with non-iron fortified foods and inadequate weaning. To improve nutritional status, especially among infants with iron deficiencies, nutritional education for mothers with infants at the weaning age must be increased and related programs must be implemented effectively.

• Journal of Dairy Science and Biotechnology
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• v.33 no.2
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• pp.111-118
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• 2015

Probiotic, prebiotic, and synbiotic substances as well as microorganisms were added to infant formula in an attempt to influence the intestinal microflora with an aim to stimulate the growth of lactic acid bacteria, especially bifidobacteria and lactobacilli. Over the last 10 years, new synbiotic infant formulas containing probiotics and prebiotics have been proposed in order to simulate the effect of breast-feeding on the intestinal microflora. Owing to their synergistic effect, the new synbiotics are expected to be more helpful than using probiotics and prebiotics individually. Maintenance of the viability of the probiotics during food processing and the passage through the gastrointestinal tract should be the most important consideration, since a sufficient number of bacteria ($10^8cfu/g$) should reach the intended location to have a positive effect on the host. Storage conditions and the processing technology used for the manufacture of products such as infant formula adversely affect the viability of the probiotics. When an appropriate and cost-effective microencapsulation methodology using the generally recognized as safe (GRAS) status and substances with high biological value are developed, the quality of infant formulas would improve. The effect of probiotics may be called a double-effect, where one is an immunomodulatory effect, induced by live probiotics that advantageously alter the gastrointestinal microflora, and the other comprises anti-inflammatory responses elicited by dead cells. At present, a new terminology is required to define the dead microorganisms or crude microbial fractions that positively affect health. The term "paraprobiotics" (or ghost probiotics) has been proposed to define dead microbial cells (not damaged or broken) or crude cell extracts (i.e., cell extracts with complex chemical composition) that are beneficial to humans and animals when a sufficient amount is orally or topically administered. The fecal microflora of bottle-fed infants is altered when the milk-based infant formula is supplemented with probiotics or prebiotics. Thus, by increasing the proportion of beneficial bacteria such as bifidobacteria and lactobacilli, prebiotics modify the fecal microbial composition and accordingly regulate the activity of the immune system. Therefore, considerable attention has been focused on the improvement of infant formula quality such that its beneficial effects are comparable to those of human milk, using prebiotics such as inulin and oligosaccharides and potential specific probiotics such as bifidobacteria, which selectively stimulate the proliferation of beneficial bacteria in the microflora and the indigenous intestinal metabolic activity of the microflora.