Ki Sook Hong

Dissemination of Macrolide-Resistant Streptococcus pneumoniae Isolates Containing Both erm(B) and mef(A) in South Korea

ABSTRACT Macrolide resistance was detected in 64 of 77 (83.1%) Streptococcus pneumoniae isolates from South Korea. Seven (10.9%) isolates contained only mef(A), 32 (50%) contained only erm(B), and 25 (39.1%) contained mef(A) and erm(B). Nineteen isolates containing mef(A) and erm(B) belonged to serotype 19F, and seven isolates were identical to the Taiwan19F-14 clone.

The methylenetetrahydrofolate reductase C677T gene mutation is associated with hyperhomocysteinemia, cardiovascular disease and plasma B-type natriuretic peptide levels in Korea.

Abstract Background: Hyperhomocysteinemia is known to be a risk factor for cardiovascular diseases and is associated with a common mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (677 C>T). The aims of this study were to confirm: 1) the association between the MTHFR C677T mutation and plasma homocysteine (Hcy) levels; 2) the MTHFR C677T mutation as a risk factor; 3) the association of the MTHFR C677T mutation and plasma B-type natriuretic peptide (BNP) levels; and 4) the correlation between Hcy and BNP levels in cardiovascular diseases. Methods: A total of 227 patients for whom BNP was measured were enrolled in this study. Laboratory parameters included BNP, creatine kinase (CK), the myocardial isoenzyme of CK (CK-MB), troponin I (TnI), Hcy, C-reactive protein (CRP), lactate dehydrogenase (LDH), creatinine and folate. The MTHFR genotype was evaluated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was shown by an electrophoretic technique. Results: The prevalence of TT homozygotes was significantly higher in patients with cardiovascular diseases than in patients without cardiovascular diseases (p=0.0001). Patients homozygous for the TT mutation had the highest plasma Hcy levels compared with wild-type CC homozygotes and CT mutant heterozygotes (p=0.0001). Plasma BNP concentrations were significantly higher in patients with MTHFR C677T mutation compared to patients without the mutation (p<0.05). Plasma BNP concentrations were positively correlated with Hcy concentrations (r=0.196, p<0.001). Multivariate logistic regression analysis showed that elevated concentrations of BNP, CRP, Hcy and the presence of the MTHFR C677T mutation independently contributed to the prediction of cardiovascular diseases. Conclusions: In cardiovascular diseases, the MTHFR C677T mutation: 1) is associated with plasma Hcy levels; 2) is an independent risk factor for cardiovascular diseases, 3) is associated with plasma BNP levels, and 4) plasma Hcy levels are positively correlated with plasma BNP levels. Clin Chem Lab Med 2006;44:1070–5.

Immunophenotypic Features of Granulocytes, Monocytes, and Blasts in Myelodysplastic Syndromes

BACKGROUND Despite the diagnostic utility of immunophenotyping for myelodysplastic syndromes (MDS), it has not been widely performed, and reports on this are absent in Korea. We aimed to evaluate the immunophenotypic features of non-blastic granulocytes, monocytes, and blasts in patients with MDS and non-clonal disorders using routine flow cytometry (FCM). Moreover, we evaluated the phenotypic abnormalities of mature cells in leukemic patients. METHODS Marrow aspirates from 60 patients, including 18 with MDS, 18 with leukemia, and 24 with non-clonal disorders (control group), were analyzed using FCM. Blasts, non-blast myeloid cells, and monocytes were gated based on CD45 expression and side scatter (SSC). The phenotypes were then compared among the 3 groups. RESULTS Compared to non-clonal disorders, the granulocytic lineages of MDS showed decreased SSC (P=0.005), increased CD45 intensity (P=0.020), decreased CD10-positive granulocytes (P= 0.030), and a higher CD56-positive rate (P=0.005). It is noteworthy that similar results were obtained in the leukemia group, and these findings were not related to the phenotypes of the leukemic cells. Using blast and monocytic gating, useful parameters for generating a differential diagnosis were not found. CONCLUSIONS Gating the granulocytic region is a relatively easy method for MDS immunophenotyping. Among the parameters studied, SSC, CD10, and CD56 were the most useful for differentiating MDS from non-clonal disorders. While immunophenotypic changes in MDS appear to be useful for differentiating MDS from non-clonal disorders, these changes were also noted in the mature cells of leukemic patients.

Hemoglobin Yamagata: hemoglobin variant detected by HbA1c Test.

Hemoglobin (Hb) Yamagata is a rare Hb variant, which has been reported only twice-one case each in Japan and Korea. This variant arises from a Lys --> Asn substitution due to a mutation of AAA to AAC or AAT at codon 133 of the beta-globin gene. This study reports the third case of a patient detected with Hb Yamagata [HBB: c.399A>T; p.Lys133Asn] and discusses the effect of this variant on HbA1c measurement. This variant was detected in a 70-yr-old Korean man with diabetes mellitus during a routine follow-up. The HbA1c concentration determined using Variant ll Turbo (Bio-Rad, USA) was abnormally high at 47.9%. It was impossible to measure the HbA1c level accurately using Variant ll Thalassemia Mode (Bio-Rad, USA). However, the HbA1c levels analyzed by HLC-723 G7 (Tosoh, Japan), Cobas Integra (Roche, Switzerland) and NycoCard (Axis-Shield, Norway) were 5.0%, 8.0%, and 7.9%, respectively. This study shows that Hb Yamagata interferes with the accurate measurement of HbA1c levels in a diabetic patient. Taking these findings into consideration, we think that an immunoassay or affinity chromatography can be used as an alternate method for measuring the HbA1c level in a patient with this variant. In conclusion, a patient can be inferred to have an Hb variant if the HbA1c concentration is abnormally high or low or if there is a discrepancy between the results obtained using different methods, and if the clinical status of the patient suggests the presence of abnormal Hb. Subsequently, the HbA1c values can be determined by methods based on different principles.

Iron removal with phlebotomy and recombinant human erythropoietin in secondary hemochromatosis after allogeneic bone marrow transplantation

Correspondence: Kyung-Ha Ryu, Department of Pediatrics, Ewha Womans University College of Medicine, 911 – 1 Mok – 6 – Dong, Yangchon-gu, Seoul 158 – 710, Korea. Email: ykh@ewha.ac.kr Received 4 March 2004; accepted 9 February 2005. Hemochromatosis, the deposition of ferritin and hemosiderin, causes liver, pancreas and heart failure. This may be caused by a congenital enzymatic defect or it can occur after multiple transfusions of packed red cells. 1 We report here a girl, 4 years after autologous peripheral blood stem cell transplantation (PBSCT) for acute myelogenous leukemia (AML) M2, who was diagnosed with secondary hypoplastic myelodysplastic syndrome (MDS). Allogeneic bone marrow transplantation (BMT) was done for the hypoplastic MDS and she received 400 mL of transfusions during that time. After the allogeneic BMT, secondary hemochromatosis and chronic graft versus host disease (GVHD) was diagnosed. She was treated with cyclosporin A and prednisone for the treatment of GVHD, and regular phelobotomy and recombinant human erythropoietin (rhEPO) were used to remove the iron while maintaining the hemoglobin level above 8 mg/dL. We sought an explanation for the high level of ferritin and came up with the following hypotheses. There have been reports of hemochromatosis in patients with MDS from ineffective erythropoiesis causing an excess of ineffectively used iron. Another possibility is that it could have become overt incidentally after the allogeneic BMT, or a new mutation in the gene might have been induced by the cytotoxic therapy. Hemochromatosis also could have evolved as a manifestation of the chronic GVHD in the liver. Possibly an underlying liver dysfunction could have caused a disturbance in the iron metabolism as well. All of these plausible causes might have been acting alone or in synergistic combination in our patient. Case report

Assessment of Therapeutic Drug Monitoring of Vancomycin in Elderly Patients According to New Guidelines

Background Concerns regarding increasing microbial resistance to vancomycin have resulted in recommendations for a higher trough serum vancomycin concentration. This study aimed to assess the dosage guidelines targeting vancomycin trough concentrations of 15-20 mg/L. Methods About 216 adult patients (age, >60 yr) were treated with intravenous vancomycin. The patients were divided into 2 groups according to their target vancomycin trough concentrations: the previous guideline group (n=108) treated with targeted vancomycin trough concentrations of 5-15 mg/L from Jan 2009 through April 2011 and the new guideline group (n=108) treated with targeted concentrations of 15-20 mg/L from November 2011 through July 2012. Results The 2 groups were not significantly different with respect to age, weight, initial serum creatinine, initial creatinine clearance, predictive trough levels, doses, serum drug concentrations, and area under the curve/minimal inhibitory concentrations. Regarding the proportions of vancomycin trough concentrations, the target range was achieved in 50% in the previous guideline group and in 16% in the new guideline group. In the previous and new guideline groups, the trough concentrations of 10-20 mg/dL were observed in 32.4% and 52.8% patients, respectively, and those of <10 mg/L were observed in 45.4% and 29.6%, respectively. Conclusions Compared to the previous guideline group, the new guideline group showed higher proportions in the therapeutic range of 10-20 mg/L and lower proportions in trough concentrations <10 mg/L. The strictly managed vancomycin therapeutic drug monitoring in the new guideline group was assessed as more effective.

Clinical Significance of Minor Elevation of Cardiac Troponin I

BACKGROUND Cardiac troponin I (cTnI) is known as a sensitive and specific marker for myocardial ischemia. The purposes of this study are to establish cut-off values of cTnI for acute myocardial infarction (AMI) and to analyze clinical significance of minor elevation of cTnI. METHODS Two hundred and four patients from whom cTnI was measured at Ewha Womans University Dongdaemun hospital from January to March, 2006 were enrolled in the study. cTnI was measured using Dimension RxL (Dade Behring, USA). The lower limit of detection (LLD), 10% CV value, 99th percentile of healthy individuals, and cut-off value for AMI by ROC curve analysis were determined. RESULTS LLD, 10% CV value, and 99th percentile of cTnI were 0.00 ng/mL, 0.10 ng/mL, and 0.07 ng/mL, respectively. The cut-off value of peak cTnI for AMI by ROC curve analysis was 0.13 ng/mL with the sensitivity, specificity, and AUC of 90.9%, 87.7%, and 0.921, respectively. The peak value of cTnI of patients with ischemic heart disease (IHD) was higher than that of the patients without IHD (P<0.05). According to the above reference and cut-off values of the initial cTnI, patients were categorized into four groups; < or =0.05 ng/mL (group 1), 0.06-0.09 ng/mL (group 2), 0.10-0.59 ng/mL (group 3), > or =0.60 ng/mL (group 4), and compared frequencies of AMI, IHD, cardio vascular disease (CVD) and death after 1 month among groups. Frequencies of AMI, IHD, CVD, and death after 1 month were significantly increased as the cTnI concentrations were increased (P<0.05). CONCLUSIONS Minor elevation of cTnI value, even in group 3 was significantly associated with high incidence of AMI, IHD, CVD, and death rate after 1 month.

Accuracy Assessment of Five Equations Used for Estimating the Glomerular Filtration Rate in Korean Adults

Background We aimed to assess the performance of the five creatinine-based equations commonly used for estimates of the glomerular filtration rate (eGFR), namely, the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr), Asian CKD-EPI, revised Lund–Malmö (revised LM), full age spectrum (FAS), and Korean FAS equations, in the Korean population. Methods A total of 1,312 patients, aged 20 yr and above who underwent 51Cr-EDTA GFR measurements (mGFR), were enrolled. The bias (eGFR–mGFR) and precision (root mean square error [RMSE]) were calculated. The accuracy (P30) of four eGFR equations was compared to that of the CKD-EPIcr equation. P30 was defined as the percentage of patients whose eGFR was within±30% of the mGFR. Results The mean bias (mL·min-1·1.73 m-2) of the five eGFR equation was as follows: CKD-EPIcr, -0.6; Asian CKD-EPI, 2.7; revised LM, -6.5; FAS, -2.5; and Korean FAS, -0.2. The bias of the Asian CKD-EPI, revised LM, and FAS equations showed a significant difference from zero (P<0.001). The RMSE values were as follows: CKD-EPIcr, 15.6; Asian CKD-EPI, 15.6; revised LM, 17.9; FAS, 16.3; and Korean FAS, 15.8. There were no significant differences in the P30 except for the Asian CKD-EPI equation: CKD-EPIcr, 76.6%; Asian CKD-EPI, 74.7%; revised LM, 75.8%; FAS, 76.0%; and Korean FAS, 75.8%. Conclusions The CKD-EPIcr and Korean FAS equations showed equivalent analytical and clinical performances in the Korean adult population.

Diagnostic Utility of Serum Glycated Albumin for Diabetes Mellitus and Its Correlation With Hyperlipidemia

Background Glycated albumin (GA) is a better marker of short-term glycemic control than glycated hemoglobin (A1c). Dyslipidemia is the main cause of cardiovascular complications in diabetes mellitus (DM). Studies on the correlation of GA with lipid indices are sparse. We investigated the diagnostic utility of GA for DM and its relationship with serum lipid profiles compared with that of A1c. Methods The GA enzymatic method was used to determine the diagnostic utility of GA for DM by using samples from 163 normal subjects (group 1) and 102 patients newly diagnosed with type 2 DM (T2DM; group 2). To analyze the lipid profiles, 263 patients with T2DM receiving treatment (group 3) were recruited. Results GA correlated with A1c (r=0.934, P<0.0001). Linear regression analysis indicated that GA levels were about 2.48 folds those of A1c. In the ROC analysis for GA to diagnose DM, the areas under the curve (0.988, 95% confidence interval 0.972-1.004) was excellent. HDL levels were significantly lower in groups 2 and 3. In group 1, positive correlations were observed between A1c and triglyceride (TG), total cholesterol (TC), LDL, TG/HDL, TC/HDL, and LDL/HDL levels. A negative correlation was observed between HDL and A1c levels. In group 3, HDL levels (P=0.0124 and P=0.0141, respectively) were significantly higher and LDL levels tended to be lower, not statistically significant, in the well-controlled group categorized using the A1c and GA cut-off values. Conclusions GA is a potential diagnostic tool for DM. Compared with A1c, GA seems less relevant to dyslipidemia.

A case of type 2N von Willebrand disease with homozygous R816W mutation of the VWF gene in a Nepalese woman

Type 2N von Willebrand disease (vWD) can be confused with hemophilia A due to decreased factor VIII levels and a bleeding tendency, and differential diagnosis is of importance for providing the optimal treatment and genetic counseling. For the accurate diagnosis of type 2N vWD, von Willebrand Factor (vWF) function tests, multimer assay and gene mutation analysis are needed. The patient was a 38-yr-old Nepalese woman with a history of bleeding manifestations from childhood, such as hemarthrosis, intramuscular hematoma, and menorrhagia. Family history revealed that her mother and elder brothers also had bleeding manifestations from childhood. When she had a laparotomy in 1991, she was diagnosed as hemophilia A with factor VIII level of 3.6% and was transfused with whole blood, factor VIII and cryoprecipitates. In June 2007, she was admitted to our hospital for further evaluation of bleeding tendency. Blood tests revealed normal CBC; bleeding time, 2 min; PT, 14.9 sec (11-14 sec); aPTT, 51.2 sec (24-38 sec); and factor VIII, 4.9% (50-150%). The prolonged aPTT was corrected by 1:1 mixing test to the levels of 106% and 84%, respectively, before and after 2 hr-incubation at 37degrees C. No abnormalities were found in the vWF antigen level (71.3%), ristocetin cofactor assay (130.4%), and multimer assay. Direct DNA sequencing of the VWF gene revealed homozygous missense mutation located in exon 19, c.2446C>T (p.Arg816Trp), confirming the diagnosis of type 2N vWD.