Background/Aims: While switching strategies of P2Y12 receptor inhibitors (RIs) have sometimes been used in acute myocardial infarction (AMI) patients, the current status of in-hospital P2Y12RI switching remains unknown. Methods: Overall, 8,476 AMI patients who underwent successful revascularization from Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) were divided according to in-hospital P2Y12RI strategies, and net adverse cardiovascular events (NACEs), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), stroke, or thrombolysis in myocardial infarction (TIMI) major bleeding during hospitalization were compared. Results: Patients with in-hospital P2Y12RI switching accounted for 16.5%, of which 867 patients were switched from clopidogrel to potent P2Y12RI (C-P) and 532 patients from potent P2Y12RI to clopidogrel (P-C). There were no differences in NACEs among the unchanged clopidogrel, the unchanged potent P2Y12RIs, and the P2Y12RI switching groups. However, compared to the unchanged clopidogrel group, the C-P group had a higher incidence of non-fatal MI, and the P-C group had a higher incidence of TIMI major bleeding. In clinical events of in-hospital P2Y12RI switching, 90.9% of non-fatal MI occurred during pre-switching clopidogrel administration, 60.7% of TIMI major bleeding was related to pre-switching P2Y12RIs, and 71.4% of TIMI major bleeding was related to potent P2Y12RIs. Only 21.6% of the P2Y12RI switching group switched to P2Y12RIs after a loading dose (LD); however, there were no differences in clinical events between patients with and without LD. Conclusions In-hospital P2Y12RI switching occurred occasionally, but had relatively similar clinical outcomes compared to unchanged P2Y12RIs in Korean AMI patients. Non-fatal MI and bleeding appeared to be mainly related to pre-switching P2Y12RIs.

PURPOSE: We aimed to identify the impact of NUDT15 variants on thiopurine intolerance and 6-thioguanine nucleotide (6-TGN) levels in Korean children with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Genotyping of NUDT15 was tested in 258 patients with ALL registered at Samsung Medical Center. Patients were classified into normal-activity (wild-type), intermediate-activity (heterozygous variant), and low-activity groups (homozygous or compound heterozygous variant). Clinical and laboratory features during the first year of maintenance therapy were investigated. RESULTS: A total of 182 patients were included in the final analysis. There were five (2.7%), 46 (25.3%), and 131 (72.0%) patients in low-, intermediate-, and normal-activity groups, respectively. The lowest 6-mercaptopurine (6-MP) dose (mg/m2/day) was administered to the low-activity group (low-activity group 7.5 vs. intermediate-activity group 24.4 vs. normalactivity group 31.1, p < 0.01) from three months to a year after beginning maintenance therapy. The low-activity group experienced the longest duration of therapy interruption during the first year (low-activity group 169 days vs. intermediate-activity group 30 days vs. normal-activity group 16 days, p < 0.01). They also showed the lowest blood cell counts and had a longer duration of leukopenia (low-activity group 131 days vs. intermediate-activity group 92 days vs. normal-activity group 59 days, p < 0.01). 6-TGN level and its ratio to 6-MP dose were lowest in the low-activity group. CONCLUSION: NUDT15 variants cause hematopoietic toxicity with low 6-TGN levels. NUDT15 genotyping should be conducted before administering thiopurine, and dose adjustments require caution regardless of 6-TGN levels.
6-Mercaptopurine ; Blood Cell Count ; Child* ; Humans ; Leukemia ; Leukopenia ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Thioguanine

Neuroblastoma (NB) is the most common extra-cranial solid tumor of childhood and is characterized by a wide range of clinical behaviors. Amplification of MYCN is a well-known poor prognostic factor in NB patients. As the MYCN amplification status is usually tested using tumor specimens, lengthy and invasive procedures are unavoidable. To evaluate the possibility of detecting MYCN amplification without invasive procedure, we performed conventional polymerase chain reaction (PCR) analysis to identify MYCN amplification using the preserved serum DNA. PCR of serum DNA was done in 105 NB patients whose MYCN status had been confirmed by fluorescence in situ hybridization. MYCN amplification was evaluated as the ratio of signal intensities between MYCN and NAGK (M/N ratio). When regarding the tissue FISH results as a reference, 10 patients had MYCN-amplified (MNA) NB, and 95 had non-MNA NB. The M/N ratio of the MNA group (median 2.56, range 1.01-3.58) was significantly higher than that of the non-MNA group (median 0.97, range 0.67-5.18) (P < 0.001). In the receiver operating characteristic curve analysis, the area under the curve was 0.957 (95% confidence interval 0.898-1.000; P < 0.001), and it showed 90.9% sensitivity and 97.9% specificity with the selected cut-off value set as 1.6. The detection of MYCN amplification using conventional PCR analysis of serum samples seems to be a simple and promising method to evaluate the MYCN status of NB patients. Further study with a larger set of patients is needed to confirm the accuracy of this result.
DNA* ; Fluorescence ; Humans ; In Situ Hybridization ; Methods ; Neuroblastoma ; Polymerase Chain Reaction* ; ROC Curve ; Sensitivity and Specificity

This study was performed to investigate the expression of two porcine endogenous retrovirus (PERV) elements, PERV gag and full-length conserved PERV, in blood cells collected periodically from organ-recipient monkeys that underwent pig to non-human primate xenotransplantation. The heart and kidney-respectively acquired from alpha-1,3-galactosyltransferase knockout (GT-KO) pigs that survived for24 and 25 days-were xenografted into cynomolgus monkeys. The two PERV elements expressed in the xenografted GT-KO pig organs were not present in the blood cells of the recipient monkeys. In the present study, we deduced that PERVs are not transmitted during GT-KO pig to monkey xenotransplantation.
Blood Cells ; Endogenous Retroviruses* ; Haplorhini* ; Heart ; Heterografts ; Macaca fascicularis ; Primates ; Swine ; Transplantation, Heterologous*

PURPOSE: This study compared outcomes in children with acute leukemia who underwent transplantations with umbilical cord blood (UCB), bone marrow, or peripheral blood stem cells from a human leukocyte antigen (HLA)-matched related donor (MRD) or an unrelated donor (URD). METHODS: This retrospective study included consecutive acute leukemia patients who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) at Samsung Medical Center between 2005 and 2010. Patients received stem cells from MRD (n=33), URD (n=46), or UCB (n=41). RESULTS: Neutrophil and platelet recovery were significantly longer after HSCT with UCB than with MRD or URD (P<0.01 for both). In multivariate analysis using the MRD group as a reference, the URD group had a significantly higher risk of grade III to IV acute graft-versus-host disease (GVHD; relative risk [RR], 15.2; 95% confidence interval [CI], 1.2 to 186.2; P=0.03) and extensive chronic GVHD (RR, 6.9; 95% CI, 1.9 to 25.2; P<0.01). For all 3 donor types, 5-year event-free survival (EFS) and overall survival were similar. Extensive chronic GVHD was associated with fewer relapses (RR, 0.1; 95% CI, 0.04 to 0.6; P<0.01). Multivariate analysis showed that lower EFS was associated with advanced disease at transplantation (RR, 3.2; 95% CI, 1.3 to 7.8; P<0.01) and total body irradiation (RR, 2.1; 95% CI, 1.0 to 4.3; P=0.04). CONCLUSION: Survival after UCB transplantation was similar to survival after MRD and URD transplantation. For patients lacking an HLA matched donor, the use of UCB is a suitable alternative.
Blood Platelets ; Bone Marrow ; Child ; Disease-Free Survival ; Fetal Blood ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukemia ; Leukocytes ; Multivariate Analysis ; Neutrophils ; Recurrence ; Retrospective Studies ; Stem Cells ; Tissue Donors ; Transplants ; Umbilical Cord ; Unrelated Donors ; Whole-Body Irradiation

PURPOSE: This study compared outcomes in children with acute leukemia who underwent transplantations with umbilical cord blood (UCB), bone marrow, or peripheral blood stem cells from a human leukocyte antigen (HLA)-matched related donor (MRD) or an unrelated donor (URD). METHODS: This retrospective study included consecutive acute leukemia patients who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) at Samsung Medical Center between 2005 and 2010. Patients received stem cells from MRD (n=33), URD (n=46), or UCB (n=41). RESULTS: Neutrophil and platelet recovery were significantly longer after HSCT with UCB than with MRD or URD (P<0.01 for both). In multivariate analysis using the MRD group as a reference, the URD group had a significantly higher risk of grade III to IV acute graft-versus-host disease (GVHD; relative risk [RR], 15.2; 95% confidence interval [CI], 1.2 to 186.2; P=0.03) and extensive chronic GVHD (RR, 6.9; 95% CI, 1.9 to 25.2; P<0.01). For all 3 donor types, 5-year event-free survival (EFS) and overall survival were similar. Extensive chronic GVHD was associated with fewer relapses (RR, 0.1; 95% CI, 0.04 to 0.6; P<0.01). Multivariate analysis showed that lower EFS was associated with advanced disease at transplantation (RR, 3.2; 95% CI, 1.3 to 7.8; P<0.01) and total body irradiation (RR, 2.1; 95% CI, 1.0 to 4.3; P=0.04). CONCLUSION: Survival after UCB transplantation was similar to survival after MRD and URD transplantation. For patients lacking an HLA matched donor, the use of UCB is a suitable alternative.
Blood Platelets ; Bone Marrow ; Child ; Disease-Free Survival ; Fetal Blood ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukemia ; Leukocytes ; Multivariate Analysis ; Neutrophils ; Recurrence ; Retrospective Studies ; Stem Cells ; Tissue Donors ; Transplants ; Umbilical Cord ; Unrelated Donors ; Whole-Body Irradiation

There were few studies about anatomic characteristics in Korean humerus recently. In addition, there was no comparison between Westerner (European and American) and Korean in anatomic characteristics of humerus. The aims of this paper are therefore to investigate anatomic characteristics in Korean humerus and to compare them with those of Westerner humerus. The seventy-two humerus (male : 66, female : 6) were scanned by computed tomography and three dimensional (3D) models of humerus were then reconstructed from acquired cross-section images. The twenty-one anatomic characteristics of the humerus were analyzed and were measured for each humerus. From the results, humeral head vertical diameter in the present study was generally bigger than that in the previous study (p<0.05). There was no significant difference between the anatomic characteristics of the right and left humerus in the present Korean (p>0.05). Humeral head inclination angle, greater tuberosity lateral offset distance, humeral head height in Korean were generally bigger than those in Westerner (p<0.05). This study may contribute to develop an optimal implants and prostheses for the treatment of humerus fractures of Koran.
Female ; Humans ; Humeral Head ; Humerus ; Prostheses and Implants

There have been attempts to use consensus sequences or ancestor sequences for development vaccines against viruses with high diversity and variation. In this study, we generated and compared consensus sequences and ancestor sequences of nef and vif genes of HIV-1 isolated from Koreans. Phylogenetic analyses revealed that majorities of the Korean isolates were clustered to form the Korean clade within subtype B (KcB) where foreign isolates were not included. Consensus sequences inferred from the KcB as well as from all Korean isolates were almost identical but significantly different from subtype B consensus sequence or HIV-1 consensus sequence. The genetic distances from one of the Korean isolates to the other Korean isolates were much longer than to the consensus or ancestor sequences deduced from Korean isolates but similar to those of subtype B or HIV-1. Moreover, the genetic distances from the Korean isolates to the consensus sequences were shorter than to the ancestor sequences both in nef and vif genes. Thus, the consensus sequences may be useful in developing Korean-specific HIV-1 vaccine.
Consensus Sequence* ; Consensus* ; Genes, vif* ; HIV-1* ; Vaccines

BACKGROUND: The analytical performance of the Vitros ECi(R) Immunodiagnostic System on the thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and estradiol (E2) assays, which are based on electrochemical luminescence to replace the radioimmunoassay was evaluated. METHODS: The precision as measured by the NCCLS protocol and a comparison of the method were done for each TSH, FT3, FT4, and E2 assay. The functional sensitivity and linearity tests were performed for both TSH and E2. The free hormone validity test was performed for both the FT3 and FT4. RESULTS: All four analytes showed an acceptable precision. The functional sensitivities of TSH and E2 were 0.007 mIU/L, and 87 pmol/L, respectively. TSH and E2 showed excellent linearity up to 78 mIU/mL, and up to 7,700 pmol/L, respectively. The free hormone validity test showed acceptable results demonstrating accurate free hormone determination. The E2 showed a significant proportion-al bias requiring an adjustment of the reference range, However, the other analytes showed good agreement with a slight proportional bias. CONCLUSIONS: The TSH, FT3, FT4, and E2 assay by Vitros ECi(R) exhibited excellent performance overcoming the drawbacks of a conventional radioimmunoassay.
Bias (Epidemiology) ; Estradiol* ; Luminescence ; Radioimmunoassay ; Reference Values ; Thyrotropin ; Thyroxine* ; Triiodothyronine*

BACKGROUND: The aim of the study was to determine prevalence of potential heterogeneous vancomycin-resistant Staphylococcus aureus (h-VRSA) among methicillin-resistant S. aureus (MRSA) isolated in Korea by using Mu-3 agar and to determine the effect of in vitro vancomycin exposure on the resistance. METHODS: MRSAs isolated in 1980-1999 were screened for the presence of VISA or h-VRSA using Mu-3 agar. MIC of vancomycin was tested by NCCLS agar dilution and broth microdilution tests. Suspected h-VRSA were selected by vancomycin-containing media and change of resistance was determined by population analysis. A strain with Mu50 type growth was serially exposed to 8 pg/ml of vancomycin containing media and change of the vancomycin resistance was determined. RESULTS: Among the 455 MRSA isolates, 18 (3.9 %) grew on selective brain heart infusion agar (BHIA), and 354 (77,8%) on Mu-3 agar, 66 (14.5%) with Mu3 type growth and 78 (17.1%) with Mu50 type growth. MIC of vancomycin was 11 pg/ml for some of the isolates when inocula were approximately 10' CFU, but VISA was not present when tested by NCCLS broth microdilution test. Exposure of the isolates to van-cornycin raised the MIC. Serial exposure once to 8 pg/ml of vancomycin resulted in significant decrease of cells susceptible to 8-12 pg/ml of vancomycin. CONCLUSION: VISA was not present among the test isolates, but 34.2% were suspected to be potential h-VRSAs, suggesting possible emergence of VISA if vancomycin was administered prolonged period. It is considered that suitable screening media are vancomycin containing BHIA for VISA and Mu-3 agar for h-VRSA. The isolates showing Mu50 type growth on Mu-3 agar are not always VISA, but rather h-VRSA.
Agar* ; Brain ; Heart ; Korea ; Mass Screening ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Prevalence ; Staphylococcus aureus* ; Staphylococcus* ; Vancomycin Resistance ; Vancomycin*