Background: We developed an assay to measure DNA-incorporated 6-thioguanine (DNATG) and validated its clinical applicability in Korean pediatric patients with acute lymphoblastic leukemia (ALL) in order to improve individualized thiopurine treatment and reduce the life-threatening cytotoxicity. Methods: The DNA-TG assay was developed based on liquid chromatography-tandem mass spectrometry, with isotope-labeled TG-d3 and guanine-d3 as internal standards.This method was applied to 257 samples of pediatric ALL patients. The DNA-TG level was compared with erythrocyte TG nucleotide (RBC-TGN) level in relation to the TPMT and NUDT15 genotypes, which affect thiopurine metabolism, using Spearman’s rank test and repeated measure ANOVA. Results: For DNA-TG quantification, a linearity range of 10.0-5,000.0 fmol TG/µg DNA;bias for accuracy of –10.4% –3.5%; coefficient of variation for intra- and inter-day precision of 3.4% and 5.8% at 80 fmol TG/µg DNA and of 4.9% and 5.3% at 800 fmol TG/µg DNA, respectively; and recovery of 85.7%–116.2% were achieved without matrix effects or carry-over. The median DNA-TG level in the 257 samples was 106.0 fmol TG/µg DNA (interquartile range, 75.8–150.9). There was a strong correlation between DNA-TG and RBC-TGN levels (ρ = 0.68,ρ < 0.0001). The DNA-TG/RBC-TGN ratio was significantly higher in NUDT15 intermediate metabolizers (*1/*2 and *1/*3) than in patients with wildtype alleles (ρ < 0.0001). Conclusions This simple and sensitive method for measuring DNA-TG level can improve therapeutic drug monitoring for thiopurine treatment.

Purpose: We investigated whether response classification after total thyroidectomy and radioactive iodine (RAI) therapy could be affected by serum levels of recombinant human thyrotropin (rhTSH)-stimulated thyroglobulin (Tg) measured at different time points in a follow-up of patients with papillary thyroid carcinoma (PTC). Methods: A total of 147 PTC patients underwent serum Tg measurement for response assessment 6 to 24 months after the first RAI therapy. Serum Tg levels were measured at 24 h (D1Tg) and 48–72 h (D2-3Tg) after the 2nd injection of rhTSH. Responses were classified into three categories based on serum Tg corresponding to the excellent response (ER-Tg), indeterminate response (IR-Tg), and biochemical incomplete response (BIR-Tg). The distribution pattern of response classification based on serum Tg at different time points (D1Tg vs. D2-3Tg) was compared. Results: Serum D2-3Tg level was higher than D1Tg level (0.339 ng/mL vs. 0.239 ng/mL, P < 0.001). The distribution of response categories was not significantly different between D1Tg-based and D2-3Tg-based classification. However, 8 of 103 (7.8%) patients and 3 of 40 (7.5%) patients initially categorized as ER-Tg and IR-Tg based on D1Tg, respectively, were reclassified to IR-Tg and BIR-Tg based on D2-3Tg, respectively. The optimal cutoff values of D1Tg for the change of response categories were 0.557 ng/mL (from ER-Tg to IR-Tg) and 6.845 ng/mL (from IR-Tg to BIR-Tg). Conclusion D1Tg measurement was sufficient to assess the therapeutic response in most patients with low level of D1Tg. Nevertheless, D2-3Tg measurement was still necessary in the patients with D1Tg higher than a certain level as response classification based on D2-3Tg could change.

Purpose: We investigated the clinical role of F-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography(PET-CT) in the identification of the primary site and the selection of the optimal biopsy site in patients with suspectedbone metastasis of unknown primary site. Methods: The patients with suspected bone metastasis who underwent PET-CT for evaluation of primary site were enrolled inthis study. The primary sites were identified by the histopathologic or imaging studies and were classified according to the FDGuptake positivity of the primary site. To evaluate the guiding capability of PET-CT in biopsy site selection, we statisticallyanalyzed whether the biopsy site could be affected according to the presence of extra-skeletal FDG uptake. Results: Among 74 enrolled patients, 51 patients had a metastatic bone disease. The primary site was identified in 48 of 51patients (94.1%). Forty-six patients were eligible to test the association of clinical choice of biopsy site with PET positivity ofextra-skeletal lesion. The extra-skeletal biopsies were done in 42 out of 43 patients with positive extra-skeletal uptake lesions.Bone biopsies were inevitably performed in the other three patients without extra-skeletal uptake lesions. The association cameout to be significant (Fisher’s exact test, P< 0.001). Conclusion F-18 FDG PET-CT significantly contributed not only to identify the primary site but also to suggest optimal biopsysites in patients with suspected bone metastasis.

PURPOSE: Thyroglobulin (Tg) may be released from damaged residual thyroid tissues after radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC). We investigated whether altered levels of serum Tg after recombinant human thyrotropin (rhTSH)-aided RAI therapy could be a prognostic marker in patients with DTC.METHODS: We evaluated 68 patients who underwent RAI therapy after total thyroidectomy. Serum Tg levels were measured just before RAI administration (D0Tg) and 7 days after RAI therapy (D7Tg). Patients with a D0Tg level greater than 2.0 ng/mL were excluded to more precisely evaluate the injury effect of RAI in small remnant tissues. The ratioTg was defined as the D7Tg level divided by that on D0Tg. The therapeutic responses were classified as acceptable or non-acceptable. Finally, we investigated which clinicopathologic parameters were associated with therapeutic response.RESULTS: At the follow-up examination, an acceptable response was observed in 50 patients (73.5%). Univariate analysis revealed significant differences in N stage (P = 0.003) and ratioTg (acceptable vs. non-acceptable responses, 21.9 ± 33.6 vs. 3.8 ± 6.5; P = 0.006). In multivariate analysis, only ratioTg significantly predicted an acceptable response (odds ratio 1.104; 95% confidence interval 1.005–1.213; P = 0.040). A ratioTg above 3.5 predicted an acceptable response with a sensitivity of 66.0%, specificity of 83.3%, and accuracy of 70.6% (area under the curve = 0.718; P = 0.006).CONCLUSIONS: Altered levels of serum Tg after RAI therapy, calculated as the ratioTg (D7Tg/D0Tg), significantly predicted an acceptable response in patients with DTC.
Follow-Up Studies ; Humans ; Iodine ; Multivariate Analysis ; Sensitivity and Specificity ; Thyroglobulin ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy ; Thyrotropin

PURPOSE: Thyroglobulin (Tg) may be released from damaged residual thyroid tissues after radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC). We investigated whether altered levels of serum Tg after recombinant human thyrotropin (rhTSH)-aided RAI therapy could be a prognostic marker in patients with DTC. METHODS: We evaluated 68 patients who underwent RAI therapy after total thyroidectomy. Serum Tg levels were measured just before RAI administration (D0Tg) and 7 days after RAI therapy (D7Tg). Patients with a D0Tg level greater than 2.0 ng/mL were excluded to more precisely evaluate the injury effect of RAI in small remnant tissues. The ratioTg was defined as the D7Tg level divided by that on D0Tg. The therapeutic responses were classified as acceptable or non-acceptable. Finally, we investigated which clinicopathologic parameters were associated with therapeutic response. RESULTS: At the follow-up examination, an acceptable response was observed in 50 patients (73.5%). Univariate analysis revealed significant differences in N stage (P = 0.003) and ratioTg (acceptable vs. non-acceptable responses, 21.9 ± 33.6 vs. 3.8 ± 6.5; P = 0.006). In multivariate analysis, only ratioTg significantly predicted an acceptable response (odds ratio 1.104; 95% confidence interval 1.005–1.213; P = 0.040). A ratioTg above 3.5 predicted an acceptable response with a sensitivity of 66.0%, specificity of 83.3%, and accuracy of 70.6% (area under the curve = 0.718; P = 0.006). CONCLUSIONS Altered levels of serum Tg after RAI therapy, calculated as the ratioTg (D7Tg/D0Tg), significantly predicted an acceptable response in patients with DTC.

PURPOSE: This study investigated the prevalence and risk factors associated with vitamin D deficiency in children. METHODS: We analyzed the medical records of 330 patients from the age of 6 to 12, who visited the endocrinology clinic of the Department of Pediatrics at Pusan National University Hospital, from September, 2013 to May, 2014. According to their serum 25-hydroxyvitamin D (25(OH)D) levels, the patients were grouped into either the deficiency group (25(OH)D<20 ng/mL), or the sufficiency group (25(OH)D≥20 ng/mL). The differences between the 2 groups were compared. RESULTS: There were 195 patients (59.1%) who had vitamin D deficiency. Their mean serum 25(OH)D level was 14.86±3.20 ng/mL. The differences in sex, age, and pubertal status between the 2 groups were not statistically significant. Weight standard deviation score (SDS), and body mass index SDS, were significantly higher in the vitamin D deficiency group (P=0.002 for each), compared to the sufficiency group. Compared with Autumn, both Spring (odds ratio [OR], 9.7; 95% confidence interval [CI], 4.3–22.0), and Winter (OR, 5.9; 95% CI, 3.5–10.0), were risk factors for vitamin D deficiency. In multiple logistic regression analysis, only seasonal differences have been confirmed to have an effect on vitamin D deficiency. CONCLUSION: Vitamin D deficiency in children aged 6 to 12 years is very common. Spring and Winter are the most important risk factors for vitamin D deficiency. We suggest that it is necessary to supplement the guideline for the vitamin D intake according to our situation.
Body Mass Index ; Busan* ; Child* ; Endocrinology ; Humans ; Logistic Models ; Medical Records ; Pediatrics ; Prevalence ; Risk Factors ; Seasons ; Vitamin D Deficiency* ; Vitamin D* ; Vitamins*

PURPOSE: This study investigated the prevalence and risk factors associated with vitamin D deficiency in children. METHODS: We analyzed the medical records of 330 patients from the age of 6 to 12, who visited the endocrinology clinic of the Department of Pediatrics at Pusan National University Hospital, from September, 2013 to May, 2014. According to their serum 25-hydroxyvitamin D (25(OH)D) levels, the patients were grouped into either the deficiency group (25(OH)D<20 ng/mL), or the sufficiency group (25(OH)D≥20 ng/mL). The differences between the 2 groups were compared. RESULTS: There were 195 patients (59.1%) who had vitamin D deficiency. Their mean serum 25(OH)D level was 14.86±3.20 ng/mL. The differences in sex, age, and pubertal status between the 2 groups were not statistically significant. Weight standard deviation score (SDS), and body mass index SDS, were significantly higher in the vitamin D deficiency group (P=0.002 for each), compared to the sufficiency group. Compared with Autumn, both Spring (odds ratio [OR], 9.7; 95% confidence interval [CI], 4.3–22.0), and Winter (OR, 5.9; 95% CI, 3.5–10.0), were risk factors for vitamin D deficiency. In multiple logistic regression analysis, only seasonal differences have been confirmed to have an effect on vitamin D deficiency. CONCLUSION: Vitamin D deficiency in children aged 6 to 12 years is very common. Spring and Winter are the most important risk factors for vitamin D deficiency. We suggest that it is necessary to supplement the guideline for the vitamin D intake according to our situation.
Body Mass Index ; Busan* ; Child* ; Endocrinology ; Humans ; Logistic Models ; Medical Records ; Pediatrics ; Prevalence ; Risk Factors ; Seasons ; Vitamin D Deficiency* ; Vitamin D* ; Vitamins*

OBJECTIVE: To evaluate the effects of extracorporeal shockwave therapy (ESWT) on pain, function, and ultrasonographic features of chronic stroke patients with knee osteoarthritis (OA). METHODS: A total of 18 chronic stroke patients (33 knee joints) with unilateral or bilateral knee OA (Kellgren-Lawrence grade ≥1) were enrolled in this study. The patients were randomly allocated to an experimental group receiving ESWT (n=9) or a control group receiving sham ESWT (n=9). For the ESWT group, patients received 1,000 pulses weekly for 3 weeks, totaling to an energy dose of 0.05 mJ/mm² on the proximal medial tibia of the affected knee. The assessments were performed before the treatment, immediately after the first treatment, and 1 week after the last treatment using the following: the visual analog scale (VAS) for pain; patient perception of the clinical severity of OA; the Korean version of Modified Barthel Index (ambulation and chair/bed transfer); the Functional Independence Measure scale (FIM; bed/chair/wheelchair transfer, toilet transfer, walking, and stairs); and ultrasonographic features (articular cartilage thickness, Doppler activity, and joint effusion height). RESULTS: The experimental group showed a significant improvement in VAS score (4.50±1.87 to 2.71±1.38) and patient perception of the clinical severity of OA (1.87±0.83 to 2.75±0.46). The bed/chair/wheelchair transfer components of the FIM score also improved significantly (4.12±1.55 to 4.62±1.30). In terms of the ultrasonographic features, increased Doppler activity was observed in the medial knee in the experimental group immediately following ESWT. CONCLUSION: It is suggested that ESWT may reduce pain and improve function in chronic stroke patients with OA, and may increase vascular activity at the target site.
Cartilage ; High-Energy Shock Waves ; Humans ; Joints ; Knee* ; Osteoarthritis, Knee* ; Pilot Projects* ; Stroke* ; Tibia ; Ultrasonography ; Visual Analog Scale ; Walking

PURPOSE: Borage oil (BO) and safflower oil (SO) are efficacious in reversing epidermal hyperproliferation, which is caused by the disruption of epidermal barrier. In this study, we compared the antiproliferative effect of dietary BO and SO. Altered metabolism of ceramide (Cer), the major lipid of epidermal barrier, was further determined by measurement of epidermal levels of individual Cer, glucosylceramide (GlcCer), and sphingomyelin (SM) species, and protein expression of Cer metabolizing enzymes. METHODS: Epidermal hyperproliferation was induced in guinea pigs by a hydrogenated coconut diet (HCO) for 8 weeks. Subsequently, animals were fed diets of either BO (group HCO + BO) or SO (group HCO + SO) for 2 weeks. As controls, animals were fed BO (group BO) or HCO (group HCO) diets for 10 weeks. RESULTS: Epidermal hyperproliferation was reversed in groups HCO + BO (67.6% of group HCO) and HCO + SO (84.5% of group HCO). Epidermal levels of Cer1/2, GlcCer-A/B, and beta-glucocerebrosidase (GCase), an enzyme of GlcCer hydrolysis for Cer generation, were higher in group HCO + BO than in group HCO, and increased to levels similar to those of group BO. In addition, epidermal levels of SM1, serine palmitoyltransferase (SPT), and acidic sphingomyelinase (aSMase), enzymes of de novo Cer synthesis and SM hydrolysis for Cer generation, but not of Cer3-7, were higher in group HCO + BO than in group HCO. Despite an increase of SPT and aSMase in group HCO + SO to levels higher than in group HCO, epidermal levels of Cer1-7, GlcCer-A/B, and GCase were similar in these two groups. Notably, acidic ceramidase, an enzyme of Cer degradation, was highly expressed in group HCO + SO. Epidermal levels of GlcCer-C/D and SM-2/3 did not differ among groups. CONCLUSION: Dietary BO was more prominent for reversing epidermal hyperproliferation by enhancing Cer metabolism with increased levels of Cer1/2, GlcCer-A/B, and SM1 species, and of GCase proteins.
Animals ; Borago* ; Carthamus tinctorius* ; Ceramidases ; Cocos ; Diet ; Epidermis* ; Glucosylceramidase ; Guinea Pigs* ; Guinea* ; Hydrogen ; Hydrolysis ; Metabolism* ; Safflower Oil* ; Serine C-Palmitoyltransferase ; Sphingomyelin Phosphodiesterase

The Ael subgroup expresses the least amount of A antigens and could only be detected by performing the adsorption-elution test. The frequency of the Ael subgroup is about 0.001% in Koreans, and the Ael02 allele, which originates from A102, is the most frequently identified allele in the Korean population. We report a Korean family with the Ael03 allele identified by molecular genetic analysis. To the best of our knowledge, this is the first such report in Korea to date.
ABO Blood-Group System/*genetics ; Alleles ; Base Sequence ; DNA Mutational Analysis ; Exons ; Frameshift Mutation ; Humans ; Male ; Middle Aged ; Pedigree ; Phenotype ; Polymerase Chain Reaction ; Republic of Korea