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Predictors of nonresponse to intravenous immunoglobulin therapy in Kawasaki disease

  • Park, Hyo Min;Lee, Dong Won;Hyun, Myung Chul;Lee, Sang Bum
    • Clinical and Experimental Pediatrics
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    • v.56 no.2
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    • pp.75-79
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    • 2013
  • Purpose: It has been reported that 10% to 20% of children with Kawasaki disease (KD) will not respond to intravenous immunoglobulin (IVIG) treatment. In this study, we aimed to identify useful predictors of therapeutic failure in children with KD. Methods: We examined 309 children diagnosed with KD at the Kyungpook National University Hospital and the Inje University Busan Paik Hospital between January 2005 and June 2011. We retrospectively reviewed their medical records and analyzed multiple parameters in responders and nonresponders to IVIG. Results: Among the 309 children, 30 (9.7%) did not respond to IVIG. They had significantly higher proportion of neutrophils, and higher levels of aspartate aminotransferase, alanine aminotransferase (ALT), total bilirubin, and N-terminal fragment of B-type natriuretic peptide than did responders. IVIG-nonresponders had a significantly longer duration of hospitalization, and more frequently experienced coronary artery lesion, and sterile pyuria. No differences in the duration of fever at initial treatment or, clinical features were noted. Conclusion: Two independent predictors (ALT${\geq}$84 IU/L, total bilirubin${\geq}$0.9 mg/dL) for nonresponse were confirmed through multivariate logistic regression analysis. Thus elevated ALT and total bilirubin levels might be useful in predicting nonresponse to IVIG therapy in children with KD.

Low T3 syndrome in Kawasaki disease: Relation to serum levels of tumor necrosis factor-α, interleukin-6 and NT-proBNP (가와사끼병에서의 저 T3 증후군 : 혈청 tumor necrosis factor-α, interleukin-6 및 NT-proBNP 농도와의 관계)

  • Cho, Hye Kyung;Sohn, Jin A;Kim, Hae Soon;Sohn, Sejung
    • Clinical and Experimental Pediatrics
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    • v.52 no.2
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    • pp.234-241
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    • 2009
  • Purpose : We investigated the relationship between thyroid hormone and serum tumor necrosis factor (TNF-${\alpha}$), interleukin (IL-6) and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in patients with Kawasaki disease (KD). Methods : Serum levels of thyroid hormone, TNF-${\alpha}$, IL-6, and NT-proBNP were measured in 52 KD patients in the acute and subacute phase and 10 patients with acute febrile illness (control group). TNF-${\alpha}$ and IL-6 were determined by sandwich enzyme-linked immunosorbent assay (ELISA). Echocardiography was performed to detect coronary artery lesions (CAL) in KD patients. Results : Low $T_3$ syndrome occurred in 63.5% of KD patients. $T_3$ in the acute phase of KD was lower than that in the control. In KD patients, $T_3$ was lowered in the acute phase and elevated in the subacute phase, whereas TNF-${\alpha}$, IL-6 and NT-proBNP were elevated in the acute phase and decreased in the subacute phase. NT-proBNP, and IL-6 were higher in patients with low $T_3$ than in those with normal $T_3$. In addition, $T_3$ inversely correlated with IL-6 and NT-proBNP. Of the 4 patients with CAL, 3 had very low $T_3$. Compared with intravenous immunoglobulin (IVIG)-responsive patients, IVIG-resistant patients had lower $T_3$ and higher IL-6 and NT-proBNP. Conclusion : $T_3$ decreases in the acute phase of KD and normalizes in the subacute phase without thyroid hormone replacement. Low $T_3$ may be partially induced by IL-6 rather than TNF-${\alpha}$, and is strongly associated with high NT-proBNP. $T_3$ in KD may be used for the differential diagnosis, monitoring the activity of the disease, and predicting the severity of inflammation.

Relationship between vitamin D levels and intravenous immunoglobulin resistance in Kawasaki disease

  • Jun, Jae Sung;Jung, Young Kwon;Lee, Dong Won
    • Clinical and Experimental Pediatrics
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    • v.60 no.7
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    • pp.216-220
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    • 2017
  • Purpose: Vitamin D is associated with various pathological conditions such as cardiovascular diseases and cancer. We investigated the relationship between vitamin D and Kawasaki disease (KD). Methods: We performed a retrospective review of the medical records of patients with KD between February 2013 and March 2016 in Daegu Fatima Hospital. Study participants were grouped according to vitamin D serum concentration. Group 1 included patients with 25(OH)-vitamin D ${\geq}20ng/mL$. Group 2 included patients with 25(OH)-vitamin D <20 ng/mL. We analyzed the clinical characteristics and laboratory data of the 2 groups. Results: Of the 91 patients, 52 were included in group 1, and 39 in group 2. Group 1 patients had significantly higher levels of calcium, phosphate, albumin and sodium than group 2 patients did. There were no differences in clinical characteristics, but the proportion of patients with polymorphic rash was significantly higher in group 2. Resistance to intravenous immunoglobulin was more frequent in group 2 (P=0.023). No significant difference in the incidence of coronary artery complications was observed. Conclusion: Low vitamin D levels are associated with resistance to intravenous immunoglobulin therapy in KD. Vitamin D deficiency might be a risk factor for immunoglobulin resistance in KD.

Serum Nitric Oxide and Tumor Necrosis Factor-α Levels in Patients with Kawasaki Disease (가와사키병 환아에서 면역글로불린 투여 전후의 혈중 Nitric Oxide와 Tumor Necrosis Factor-α에 대한 연구)

  • Park, Ji Hye;Shin, Jee Seon;Hong, Young Mi
    • Clinical and Experimental Pediatrics
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    • v.48 no.7
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    • pp.772-778
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    • 2005
  • Purpose : Kawasaki disease(KD) is a systemic panvasculitis that causes coronary artery lesions. KD is accompanied by immunoregulatory abnormalities. Nitric oxide(NO) can induce relaxation of blood vessels by activating guanylate cyclase in smooth muscle cells and high levels of NO may result in coronary artery lesions. We investigated tumor necrosis factor$(TNF)-{\alpha}$ and NO production before and after intravenous immunoglobulin(IVIG) therapy to study the roles of NO and $TNF-{\alpha}$ in KD with coronary artery lesions. Methods : Serum levels of NO and $TNF-{\alpha}$ were measured in 24 patients with KD(group I, eight patients with normal coronary artery; group II, 16 patients with coronary artery lesions) and 23 controls(group III, 13 afebrile controls; group IV, 10 febrile controls). Blood samples from each subject were drawn before and after IVIG therapy and in the convalescent stage. Serum concentrations of NO and $TNF-{\alpha}$ were measured by enzyme linked immuno sorbent assay. Results : The NO levels before IVIG therapy were significantly higher in group II than in group I, group III and group IV. After IVIG therapy the levels of NO were significantly higher in group I and group II than in group III. The $TNF-{\alpha}$ levels before IVIG therapy were significantly higher in group I and group II than in group III. The serum $TNF-{\alpha}$ and NO levels were higher before IVIG therapy and decreased through the convalescent stage in KD patients. In the acute stage of KD patients with coronary artery lesions, serum NO levels significantly correlated with white blood cells (r=0.43, P<0.05). Conclusion : The serum concentration levels of $TNF-{\alpha}$ and NO were abnormally high in KD patients and NO concentrations were statistically higher in the KD patients with coronary artery abnormalities than those without coronary abnormality during the early stage of the KD. These results suggest NO may be involved in the development of coronary artery lesions.

Optimization of Various Organic Acids on Photo-Fermentative Hydrogen Production using Rhodobacter sphaeroides KD131 (Rhodobacter sphaeroides KD131에 의한 유기산 광합성 발효 최적화)

  • Son, Han-Na;Kim, Mi-Sun
    • Transactions of the Korean hydrogen and new energy society
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    • v.21 no.2
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    • pp.136-142
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    • 2010
  • Photobiological $H_2$ production was compared using purple non-sulfur bacteria Rhodobacter sphaeroides KD131 in the medium containing various organic acids as the carbon source and electron doner under illumination of $110\;W/m^2$ using halogen lamp at $30^{\circ}C$. The organic acids used were 0~120 mM acetate, butyrate, lactate and malate. Initial pH 7.0 and cell concentration 1.0 at 660nm were increased to pH 8 and 4.4~5.1, respectively during 24hrs of photo-fermentation when lactate and malate were used. However, acetate and butyrate increased pH to 9 and cell concentration to 3.2~3.9 of malate at the same experimental conditions. Optimum ranges of organic acids concentration and carbon/nitrogen ratio were 30~60 mM and 10~20, respectively. When malate was used as the substrate, maximum $H_2$ production 1.1 ml $H_2$/ml broth, which is equivalent to 1.97 mol $H_2$/mol malate was observed.

Purification and Characterization of Carboxymethyl-cellulase Produced by Bacillus sp. KD1014

  • Lee, Kyung-Dong;Kim, Jungho;Kim, Hoon
    • Journal of Applied Biological Chemistry
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    • v.42 no.3
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    • pp.107-112
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    • 1999
  • A carboxymethyl-cellulase (CMCase) was purified from the culture supernatant of Bacillus sp. KD1014 by ultrafiltration, ammonium sulfate precipitation, and a series of chromatography on QAE-Sephadex A-50, hydroxylapatite and Sephadex G-75. The purified CMCase was a single protein of 32 kDa, showed an optimum activity at $60^{\circ}C$ and pH 6.0, and had a half-life of 23 min at $70^{\circ}C$. The enzyme activity was not influenced by metal ions such as $Mg^{2+},\;Fe^{3+},\;K^+,\;Zn^{2+}$, and $Cu^{2+}$ at a concentration of 1.0 mM, partially inhibited by $Mn^{2+}$ and $Ag^+$, and significantly inhibited by pentachlorophenol (PCP). The purified enzyme showed a 3.9-times higher activity on lichenan than on CMC, but hardly cleaved xylan, starch, avicel, laminarin, filter paper and levan. The results of activity staining of the purified enzyme separated by native and denaturing gel electrophoresis suggested that the CMCase might exist in dimeric, oligomeric or aggregated form as well as in monomeric form. The enzymatic cleavage products from cellotetraose indicated that the CMCase possessed transglycosylation activity.

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Digestibility of nitrogen and dry matter of oilseed meals and distillers dried grains supplemented in swine diets

  • Park, Sung-Kwon;Cho, Eun-Seok;Jeong, Yong-Dae;Sa, Soo-Jin
    • Korean Journal of Agricultural Science
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    • v.43 no.5
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    • pp.769-776
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    • 2016
  • This study was conducted to investigate the digestibility of dry matter (DM) and nitrogen (N) in oilseed meals and distillers dried grains (DDG) fed to growing-finishing pigs. As experimental animals, eleven barrows (initial body weight, $71.7{\pm}17.0kg$) were housed in individual metabolism cages. The experimental design consisted of an $11{\times}8$ incomplete Latin square with 11 dietary treatments and 8 replication periods. The diets were individually formulated with dehulled soybean meal produced in Korea (SBM-KD), soybean meal produced in India (SBM-I), soybean meal produced in Korea (SBM-K), corn high-protein distiller dried grains (HPDDG), tapioca distillers dried grains (TDDG), canola meal (CAM), corn germ meal (CGM), copra meal (COM), palm kernel meal (PKM), sesame meal (SM), and perilla meal (PM). Pigs with SBM-KD and SBM-K showed greater (p < 0.05) intake of N than SBM-I, HPDDG, and PKM. Total feces output was decreased (p < 0.05) in SBMs (SBM-KD, -I, and -K), HPDDG, and CGM compared with TDDG, SM, and PM. The DM in excreted feces was decreased (p < 0.05) in SBMs and CGM compared to TDDG, SM, and PM. Similarly, the SM and PM fed to pigs resulted in greater (p < 0.05) fecal excretion of N than the others. Apparent total tract digestibility (ATTD) of DM in SBMs and CGM was greater (p < 0.05) than TDDG, SM, and PM. The SBMs fed to pigs showed higher (p < 0.05) ATTD of N than TDDG, COM, SM, and PM. In conclusion, our results provided nutritional information about various ingredients and would be useful to contain more precise amounts of nutrients included in feed ingredients of pig diet.

Prediction of unresponsiveness to second intravenous immunoglobulin treatment in patients with Kawasaki disease refractory to initial treatment

  • Seo, Euri;Yu, Jeong Jin;Jun, Hyun Ok;Shin, Eun Jung;Baek, Jae Suk;Kim, Young-Hwue;Ko, Jae-Kon
    • Clinical and Experimental Pediatrics
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    • v.59 no.10
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    • pp.408-413
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    • 2016
  • Purpose: This study investigated predictors of unresponsiveness to second-line intravenous immunoglobulin (IVIG) treatment for Kawasaki disease (KD). Methods: This was a single-center analysis of the medical records of 588 patients with KD who had been admitted to Asan Medical Center between 2006 and 2014. Related clinical and laboratory data were analyzed by univariate and multivariate logistic regression analyses. Results: Eighty (13.6%) of the 588 patients with KD were unresponsive to the initial IVIG treatment and received a second dose. For these 80 patients, univariate analysis of the laboratory results obtained before administering the second-line IVIG treatment showed that white blood cell count, neutrophil percent, hemoglobin level, platelet count, serum protein level, albumin level, potassium level, and C-reactive protein level were significant predictors. The addition of methyl prednisolone to the second-line regimen was not associated with treatment response (odds ratio [OR], 0.871; 95% confidence interval [CI], 0.216-3.512; P=0.846). Multivariate analysis revealed serum protein level to be the only predictor of unresponsiveness to the second-line treatment (OR, 0.160; 95% CI, 0.028-0.911; P=0.039). Receiver operating characteristic curve analysis to determine predictors of unresponsiveness to the second dose of IVIG showed a sensitivity of 100% and specificity of 72% at a serum protein cutoff level of <7.15 g/dL. Conclusion: The serum protein level of the patient prior to the second dose of IVIG is a significant predictor of unresponsiveness. The addition of methyl prednisolone to the second-line regimen produces no treatment benefit.

Electron Dosimetry of Shaped Fields on Mevatron KD 67-7467 (Mevatron KD 67-7467의 변형조사면에 대한 전자선 선량측정)

  • U Hong;Samuel Ryu;H. D. Kang
    • Progress in Medical Physics
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    • v.1 no.1
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    • pp.109-122
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    • 1990
  • A method of making inserts for shaped fields in electron beam therapy on the Mevatron KD 67-7467 Linear Acclerator is introduced. The inserts are made from an alloy called Lipowitz metal. These are designed to fit the inside of the standard Siemens cones. Studies have shown that this method does not adversely affect field flatness. However, if the ratio of shaped field to open field is greater than about 70%, the output dose is significantly changed by the inserts. Because the cone ratios for the fields do not follow the open cone ratio curves on the Mevatron KD 67-7467, we separated the cone ratio suggested by Biggs into two parts, the insert ratio and the cone factor. The dosimetry for these shaped beams has been investigated extensively.

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Epidemiologic study of Kawasaki disease in 6 months old and younger infants (6개월 이하 영아에서의 가와사끼병의 역학적 연구)

  • Park, Yong Won;Han, Ji Whan;Park, In Sook;Kim, Chang Hwi;Cha, Sung Ho;Ma, Jae Sook;Lee, Joon Sung;Kwon, Tae Chan;Lee, Sang Bum;Kim, Chul Ho;Lee, Heung Jae;Yun, Yong Soo
    • Clinical and Experimental Pediatrics
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    • v.51 no.12
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    • pp.1320-1323
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    • 2008
  • Purpose : The aim of this study was to investigate the epidemiologic status of Kawasaki disease (KD) in infants ${\leq}6months$ of age. Methods : For the epidemiologic study of KD in Korea, data from 22,674 KD patients were collected from 1997 to 2005 on a 3-year basis by a retrospective survey. From this survey, data of 1,739 KD patients ${\leq}6months$ of age were analyzed and compared with those of KD patients >6 months of age. Results : A total of 1,739 patients ${\leq}6months$ of age, including 1,088 males and 651 females, represented 7.7% of total KD patients. These subjects included 22 patients aged <1 month, 171 patients aged 1-2 months, 304 patients aged 2-3 months, 407 patients aged 3-4 months, 372 patients aged 4-5 months, and 463 patients aged 5-6 months. Their mean age of onset was 4.3 months, and the male-to-female ratio was 1.67:1. Incidences of coronary arterial (CA) abnormalities (21.0% versus 18.7%) and CA aneurysms (4.7% versus 3.1%) detected by echocardiography showed differences between patients with KD younger and older than 6 months, respectively. Conclusion : Comparison of data from KD patients >6 months old with data from 1,739 KD patients ${\leq}6months$ old showed significantly higher incidences of CA abnormalities and CA aneurysms in the younger patients.