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Background: We assessed whether glycated albumin (GA) is a useful glycemic indicator in diabetic patients with anemia who did not undergo dialysis. Methods: Hemoglobin A1c (HbA1c) and GA were simultaneously measured in 370 diabetic subjects who had not undergone dialysis. The relationship between GA and HbA1c was evaluated in patients with and without anemia. Results: GA-to-HbA1c ratio was significantly higher (3.3±0.7 vs. 2.8±0.5, p<0.001) and the regression slope between GA and HbA1c was steeper in diabetic patients with than in those without anemia (6.2 vs. 4.2, p<0.001). Conclusions: HbA1c was underestimated in diabetic patients with anemia than in those without anemia, with the degree of underestimation increasing as glycemic control became poorer. GA may more accurately assess glycemic control in diabetic patients with anemia than HbA1c. [ABSTRACT FROM AUTHOR]

Background/aim: Endothelial dysfunction due to reduced nitric oxide (NO) availability precedes the development of atherosclerosis. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is not only a cause of endothelial dysfunction, but also a predictor of the cardiovascular outcome in end-stage renal disease (ESRD) patients on hemodialysis (HD). Alpha-lipoic acid (ALA), a strong antioxidant, increases NO-mediated vasodilation in diabetic patients. We investigated whether ALA could decrease the plasma level of ADMA in diabetic ESRD patients on HD.Methods: Fifty patients undergoing HD three times per week were randomized to a treatment group receiving ALA 600 mg/day for 12 weeks or a control group. We measured the plasma levels of cholesterol, albumin, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, hemoglobin A1c, and ADMA in both groups at baseline and at 12 weeks.Results: In the control group, the levels of total cholesterol, serum albumin, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, hemoglobin A1c, and ADMA did not change. In the treatment group, the plasma levels of ADMA decreased significantly from a median of 1.68 (range 0.45-3.78) microM to a median of 1.31 (range 0.25-3.19) microM (p = 0.001).Conclusion: Considering that ADMA is an independent risk factor for cardiovascular outcome in ESRD patients, ALA may have the potential of a beneficial effect in them, in part by decreasing the plasma level of ADMA. [ABSTRACT FROM AUTHOR]

: ObjectivesSmall dense LDL, low density lipoprotein (LDL) particles with small size and high density, is regarded as a significant risk factor for cardiovascular diseases. Diabetes mellitus is one of the conditions accompanied by increased small dense LDL. We analyzed LDL subclass in type 2 diabetics and normal controls with LipoPrint LDL System to investigate the LDL heterogeneity in diabetics and factors affecting it.: Design and methodsWe selected 40 normal controls and 40 type 2 diabetics with fasting blood glucose level over 7.0 mmol/L and HbA1c level over 7%. LDL subclass was determined with LipoPrint LDL System. LipoPrint LDL System fractionates LDL into seven parts (LDL1-7) by size and LDL3 to LDL7 are defined as small-sized LDL. In addition we estimated ‘the percent of small-sized LDL over whole LDL’ and defined it as ‘small-sized LDL proportion’.: ResultsMean small-sized LDL proportion was significantly higher in diabetics (23.4%) than in controls (11.8%) (p < 0.001) and small-sized LDL proportion showed positive correlation with blood levels of glucose, HbA1c, total cholesterol, triglyceride, and oxidized LDL and negative correlation with HDL cholesterol level in univariate analysis (p < 0.001). Of these parameters, triglyceride, HbA1c, oxidized LDL were statistically significant variables contributing to the small-sized LDL proportion in stepwise multiple regression analysis.: ConclusionsWe analyzed small-sized LDL proportion in type 2 diabetics and found that it was significantly increased in diabetics than control subjects and it was independently correlated with triglyceride, HbA1c, oxidized LDL in descending order, which are reflecting lipid metabolism, glycation, and oxidative stress, respectively. [Copyright &y& Elsevier]

Background: Genetic variants may play a role in determining the location of cerebral atherosclerosis. We aimed to investigate the association between RNF213, MMP2, and genetic polymorphisms linked to vascular tortuosity with the location of cerebral arterial atherosclerosis. Methods: A prospective case-control study was conducted on patients with ischemic stroke and age- and sex-matched stroke-free controls. The stroke patients were categorized into those with intracranial artery atherosclerosis (ICAS), extracranial artery atherosclerosis (ECAS), and small vessel occlusion (SVO). Six single nucleotide polymorphisms (SNPs) including rs2118181 (FBN1), rs2179357 (SLC2A10), rs1036095 (TGFBR2), rs243865 (MMP2), rs1800470 (TGFB1), and rs112735431 (RNF213) were analyzed with the TaqMan Genotyping Assay, and the distribution of genotypes across groups was compared. Results: None of the 6 SNPs were associated with stroke on comparing the 449 stroke patients (71 with ECAS, 169 with ICAS, and 209 with SVO) to the 447 controls. In the subgroup analysis, the adjusted odds ratios (aORs) for age and sex indicated a significant association between rs112735431 and ICAS in the allele comparison analysis and in the additive and dominant model analyses. rs112735431 was associated with anterior circulation involvement and increased burden of cerebral atherosclerosis. rs2179357 was significantly associated with ICAS in the recessive model analysis, and rs1800470 was significantly associated with ECAS in the recessive model analysis when compared to controls. Conclusion: rs112735431 was associated with ICAS and increased atherosclerosis burden in Korean stroke patients. Further studies are needed to elucidate the role of rs112735431 and to confirm the association of rs2179357 and rs1800470 with cerebral atherosclerosis. [ABSTRACT FROM AUTHOR]

Background The manual microscopic examination (MME) of urine sediment is labor-intensive, time-consuming, and imprecise. Therefore, automated urinalysis systems based on flow cytometry or digital imaging techniques could replace MME. The purpose of this study was to evaluate the rate of MME using two automated urine sediment analyzers, alone and in combination. Methods This study was conducted using the freshly collected urine specimens of 1055 in-patients and 1119 out-patients. All samples were analyzed using UF-1000i (Sysmex Corporation) and Cobas 6500 instrument (Roche Diagnostics International). The rate of MME was evaluated using two analyzers, both individually and in combination. Results Using the UF-1000i alone, 34.2% and 16.8%, respectively, of in- and out-patient samples were analyzed by MME, compared to 15.6% and 3.7%, respectively, using the Cobas 6500. In combined assay using the UF-1000i followed by the Cobas 6500, 27.9% and 11.3% in-patient samples required on-screen review and MME, respectively. And the respective rates were 10.3% and 2.7% of out-patient. Samples using the Cobas 6500 followed by the UF-1000i, 42.3% and 11.3% in-patient needed on-screen review and MME, respectively. And the respective rates were 18.9% and 2.7% of out-patient samples. Conclusions Use of the Cobas 6500 compared to the UF-1000i resulted in decreases in the rate of MME from 34.2% to 15.6% for in-patient samples, and from 16.8% to 3.7% for out-patient samples. Use of the Cobas 6500 reduced the rate of MME, and compared to use of only the Cobas 6500, the combined use resulted in a reduction in the rate of on-screen review. [ABSTRACT FROM AUTHOR]

• We evaluated the levels of KL-6 and SP-A and identified their clinical correlations in healthy individuals to assess their usefulness in the diagnosis of ILAs. • The KL-6 and SP-A cutoff values were 304 U/mL and 43.5 ng/mL between the ILD and healthy groups, respectively, which were lower than the values recommended by the manufacturer. • The results revealed an association between increased serum levels of these biomarkers and clinical characteristics as incidental findings on chest imaging and reduced lung function. • Our study findings may aid future research on the use of biomarkers in the initial work-up, monitoring, and planning the management of asymptomatic patients with risk factors. Interstitial lung abnormalities (ILAs) are associated with the risk of progression to interstitial lung diseases (ILDs). Krebs von den Lungen 6 (KL-6) and surfactant protein (SP)-A have been used as biomarkers of ILDs. In this study, we evaluated the levels of these biomarkers and identified their clinical correlations in healthy individuals to assess their usefulness in the diagnosis of ILAs. The patient samples were categorized into three groups: healthy, disease, and ILD groups. We used the automated immunoassay HISCL KL-6 and SP-A assay kits. The analytical performance evaluation involved precision, linearity, comparison, establishment of reference intervals, and determination of the cutoff points. We also analyzed the correlations between presence of abnormalities on chest radiography and computed tomography (CT) or pulmonary function test (PFT) and serum levels in the healthy group. KL-6 and SP-A assays showed good analytical performance. The KL-6 and SP-A cutoff values were 304 U/mL and 43.5 ng/mL between the ILD and healthy groups, respectively, which were lower than the values recommended by the manufacturer. In the clinical correlations with radiological findings, SP-A values in subjects with lung abnormalities on CT scans were significantly higher than those in normal scans. There was no significant difference in KL-6 and SP-A levels among PFT patterns; however, both serum levels in the mixed pattern showed higher values than those in the other patterns. The results revealed a positive association between increased serum levels of SP-A and KL-6 and clinical characteristics as incidental findings on chest imaging and reduced lung function. [ABSTRACT FROM AUTHOR]

Background The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was derived mostly from Caucasian, African-American, and Hispanic populations, whereas Asian populations were excluded. The aim of this study was to develop and validate a Korean version of the CKD-EPI equation. Methods The study enrolled 960 individuals 18 years old and older who underwent chromium-51-ethylenediaminetetraacetic-acid-based glomerular filtration rate (GFR) measurements. They were divided randomly into two groups: a development set (n = 768, 80%) and a validation set (n = 192, 20%). The Korean CKD-EPI equation was developed using a non-linear mixed-effect model. The performance of the equation was evaluated by calculating the bias (estimated GFR–measured GFR). The ± 10% (P10) and ± 30% (P30) accuracies and root mean square errors (RMSEs) of the original and Korean CKD-EPI equations were compared. Results The Korean CKD-EPI equation was as follows: male, serum creatinine (Scr) ≤ 80 μmol/L, GFR = 141 × (Scr/0.9) − 0.642 × (0.993) Age ; male, Scr > 80 μmol/L, GFR = 141 × (Scr/0.9) − 1.128 × (0.993) Age ; female, Scr ≤ 62 μmol/L, GFR = 144 × (Scr/0.7) − 0.465 × (0.993) Age ; female, Scr > 62 μmol/L, GFR = 144 × (Scr/0.7) − 1.382 × (0.993) Age . The mean bias (mL/min/1.73 m 2 ) of the original CKD-EPI equation was − 3.0 ± 13.5 and that of the Korean CKD-EPI equation − 2.3 ± 13.3. The P10 and P30 of the original CKD-EPI equation were 33.9% and 82.8%; for the Korean CKD-EPI equation, the corresponding values were 35.4% and 85.9%. The RMSEs of the original and Korean CKD-EPI equations were 13.7 and 13.5, respectively. Conclusions The overall analytical performance of the Korean CKD-EPI equation was equivalent to that of the original CKD-EPI equation. The original CKD-EPI equation is therefore also valid for the Korean population. [ABSTRACT FROM AUTHOR]

Background: Despite the high transferrin saturation (TS) level in Koreans, the p.Cys282Tyr and p.His63Asp mutations are markedly less frequent than in Caucasians. We aimed to determine TS levels and their familial tendencies in a Korean population using nationwide data from the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1 2010).Methods: A total of 4904 subjects without a history of hepatitis B and C virus infection, or liver cirrhosis, and who were negative for anemia and hepatitis B antigen were enrolled. A familial tendency analysis was performed in 260 families. Parents were grouped into four quartiles based on their TS levels. Offspring were categorized according to the mean parental TS four quartile scores (1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0). A familial tendency was evaluated by comparing the mean TS of offspring in seven parental groups.Results: The mean TS was 39.3 ± 15.6% for Korean males and 33.2 ± 12.9% for Korean females, and both were significantly higher than those of Caucasians reported in the HEIRS study (30.6 ± 11.0% for male, 25.6 ± 10.6% for female, P < 0.001). The 260 families showed statistically significant familial tendencies of TS values (P < 0.001). The mean TS of offspring in parental group 1.0, 1.5, 2.0, and 2.5 showed a lower value than that in higher group 3.0, 3.5, and 4.0. In contrast, there were no significant differences in age, daily dietary iron intake, and AST or ALT value among seven groups.Conclusions: These findings suggest unidentified genetic variations on high TS in Koreans beyond the p.Cys282Tyr and p.His63Asp mutations commonly identified in Caucasians. [ABSTRACT FROM AUTHOR]

Background Acute kidney injury ( AKI) is a common complication and a significant prognostic factor of long-term outcome in patients undergoing liver transplantation. We evaluated the utility of urine and plasma neutrophil gelatinase-associated lipocalin ( NGAL) concentrations as biomarkers of AKI during and after liver transplantation. Materials and methods We prospectively enrolled 19 adult patients who underwent living-related liver transplantation ( LRLT). Serial blood and urine samples were collected at baseline and at 2, 4, 10, 16, 24, 30, 40, and 48 h after reperfusion, and their concentrations of NGAL were measured, with urinary NGAL corrected by urinary creatinine concentration to compensate for urine output. AKI was defined by Risk- Injury- Failure- Loss- End-stage kidney disease ( RIFLE) criteria as a ≥50% increase in serum creatinine from baseline. Results Eleven of 19 patients were diagnosed with AKI according to RIFLE criteria. Urinary NGAL/urine creatinine ratio increased immediately after reperfusion and peaked four h later and preceded a ≥50% elevation in serum Cr by 19.0 h (p = 0.001). Plasma NGAL also tended to be elevated 13.0 h earlier than serum creatinine (p = 0.075). Conclusions The urinary NGAL/urine creatinine ratio may be an early biomarker of AKI in adult patients undergoing LRLT. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The optimal dose of the oral anticoagulant warfarin varies with polymorphisms of the vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genes. A fast and reliable method of warfarin dose adjustment is required to prevent serious hemorrhagic or thrombotic complications. The aim of this study is to develop and validate a new warfarin dose genotyping system with an automatic interpretation function. Materials and methods: Four VKORC1 and two CYP2C9 SNPs were genotyped by real-time PCR using allele-specific primers and probes. Multiple reactions that included internal positive controls were performed in each well, and an automatic interpretative algorithm was developed. This system was validated using 82 clinical specimens previously genotyped by PCR-direct sequencing. The analytical time of the method was calculated. Results: No interference was observed when multiple samples were included in each reaction, with all internal positive control reactions being successful. In the genotyping algorithm, Ct differences <2 and ≥2 identified heterozygotes and homozygotes, respectively. All results obtained were concordant with those of the reference method. The overall analytical time for assay of 12 specimens was around 3 hours. Conclusion: This rapid, accurate, and user-friendly genotyping system improves the efficacy and safety of anticoagulation therapy in clinical practice. [Copyright &y& Elsevier]

Background: New therapeutics targeting epidermal growth factor receptor (EGFR) have significantly improved tumor responses to therapy in non-small cell lung cancer (NSCLC) patients. Molecular testing for EGFR mutations informs important therapeutic decisions in clinical practice. In this study, we sought to validate the clinical relevance of sequencing-based EGFR mutation testing combined with cytological analysis using body fluid specimens. Methods: Two NSCLC cell lines were used in sensitivity analyses. In addition, we performed cytological analyses and directly sequencing of exons 18-21, for 32 specimens. The absence of EGFR mutations determined by direct sequencing in 14 specimens was confirmed by real-time PCR. Changes made to patients' therapeutic strategies after reports of EGFR mutation status were investigated by querying electronic medical records. Results: Sensitivity studies showed that detection of in-frame deletions in exon 19 and point mutations in exon 21 was possible in specimens containing 10% and 5% mutant DNA, respectively. In clinical practice, EGFR mutations were detected in 18 of 32 specimens (56.3%). Twelve patients with EGFR mutations detected by direct sequencing were started on treatment with EGFR tyrosine kinase inhibitor (TKI) after reports of EGFR mutation. EGFR-TKI therapy was discontinued for two patients with TKI-resistant T790M mutation. The results of real-time PCR were consistent with those of direct sequencing in 13 of 14 specimens (92.9%) in which no mutation was detected by direct sequencing. Conclusions: Combined direct sequencing and cytological analysis of body fluid specimen might be clinically useful and sensitive test for the detection of EGFR mutations in NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is widely used for therapeutic drug monitoring of immunosuppressants given to transplant recipients. This study evaluated the performance of the newly introduced MassTrak Immunosuppressant XE Kit (Waters Corporation; 'the Kit') in the determination of everolimus and cyclosporin A (CsA) using LC-MS/MS. Methods: The linearity, precision, detection limit, carryover and matrix effect of the Kit and comparison of the in-house method and Kit procedure were evaluated according to Clinical and Laboratory Standards Institute guidelines. Results: The Kit afforded good linearity in the measurement of everolimus from 2 to 26 ng/mL (R2=0.996) and of CsA from 42.6 to 1407 ng/mL (R2=0.995). The between- and within-run assay coefficients of variation were 2.3%-8.0% for everolimus and 1.1%-3.1% for CsA. The lower limit of quantitation of everolimus and CsA were 1.1-4.1 ng/mL, respectively. A comparison of CsA values obtained using in-house reagents indicated good correlation with Kit results (R=0.9909). The average matrix effect ranged from 15%-39% for everolimus and 3%-10% for CsA, and ion enhancement was mostly observed for the matrix effect. The effect on analyte/internal standard ratios ranged from 1%-8% for everolimus and 1%-16% for CsA. Conclusions: The Kit employing isotopically labeled internal standards provides reliable measurements of immunosuppressant levels over a broad range of concentrations. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding the assessment of the nationwide glucose proficiency testing in Korea.

Abstract: Germline mutations within the adenomatous polyposis coli (APC) gene are associated with familial adenomatous polyposis (FAP), an autosomal dominant disease predisposing individuals to colorectal cancer. Identification of APC mutations has important implications for genetic counseling and management of FAP patients. We examined the APC mutation status of 10 Korean FAP patients by polymerase chain reaction–direct sequencing method and found six APC mutations, including three novel mutations. Testing for MUTYH mutation was done for FAP patients in whom no mutation in the APC gene was identified. Three novel mutations (c.1654_1663delTCTTGGCGAG, c.3709C>T, and c.6092_6094delinsTT) and three previously reported mutations (c.3631_3632delAT, c.4438C>T, and c.4612_4613delGA) were detected. The MUTYH mutation was not detected in any of the four FAP patients without an APC mutation. This finding of three novel mutations in a group of Korean FAP patients broadens the spectrum of APC mutations. [Copyright &y& Elsevier]

We investigated whether homocysteine (Hcy)- lowering therapy or an antioxidant prevented bone loss in Parkinson's disease (PD) patients taking levodopa. Forty-two PD patients with low bone mineral density (BMD) taking levodopa were randomly assigned to Hcy-lowering therapy (5 mg folate and 1500 μg vitamin B12 daily), α-lipoic acid (α-LA) therapy (1200 mg daily), or control groups. Primary outcomes were BMD changes from baseline to 12 months. Secondary outcomes were changes in Hcy level, and C-telopeptide (CTX) levels at 12 months. Forty-one patients completed the study. Hcy-lowering therapy resulted in significantly greater BMD changes at the lumbar spine (4.4%), total femur (2.8%), and femur shaft (2.8%) than control ( P = 0.005-0.023). BMD changes in the α-LA therapy group were similar to those of the control group, but changes at the trochanter (4.6%) were significantly greater in the α-LA therapy group than in the control group after adjustment for body mass index changes. Hcy concentrations decreased to 35.2% ± 13.4% in the Hcy-lowering therapy group, but increased in other groups. Serum CTX levels at 12 months tended to be lower in the Hcy-lowering group (0.442 ± 0.024 ng/mL) than control group (0.628 ± 0.039 ng/mL) ( P = 0.159). This small trial suggests that Hcy-lowering therapy may prevent bone loss in PD patients taking levodopa. © 2009 Movement Disorder Society [ABSTRACT FROM AUTHOR]