GATA1 Expression in BCR/ABL1-negative Myeloproliferative Neoplasms.

BACKGROUND: This study aimed to determine GATA1 expression levels to better characterize subgroups in BCR/ABL1-negative myeloproliferative neoplasms (MPNs). METHODS: This study enrolled 49 patients diagnosed as having BCR/ABL1-negative MPN on the basis of the 2016 World Health Organization classification : nine polycythemia vera (PV), 17 essential thrombocythemia (ET), 12 prefibrotic primary myelofibrosis (prePMF), and 11 overt primary myelofibrosis (PMF). Relevant clinical and laboratory data were retrieved from the medical records. The molecular analysis of CALR and MPL mutations and quantification of JAK2 V617F allele burden were performed. GATA1 expression was assessed by an immunohistochemical assay on bone marrow biopsy. GATA1 expression was analyzed serially in 18 patients. RESULTS: GATA1 expression decreased significantly in PMF compared with that in other subtypes, while no statistical difference was identified between ET and prePMF. GATA1 expression did not differ according to the mutation profiles or the allele burden of JAK2 V617F, but it decreased significantly in patients with overt fibrosis or leukemic transformation. CONCLUSIONS: Our results suggest that GATA1 expression is significantly low in PMF and decreases with progressive fibrosis and possibly with leukemic transformation, although our attempt to accurately distinguish between subgroups using GATA1 immunohistochemical approach did not achieve statistical significance. A large patient cohort with long term follow-up is required to evaluate the prognostic value of GATA1 expression.

Evaluation of the 1B Equation to Estimate Glomerular Filtration Rate in Pediatric Patients with Cancer.

The 1B equation is recommended for calculating the glomerular filtration rate (GFR) in children. Since few reports have evaluated the performance of the 1B equation, we investigated the performance of estimated GFR (eGFR) equations with the blood urea nitrogen (BUN) variable for pediatric cancer patients. In total, 203 children with cancer who underwent measured GFR (mGFR) assessment were enrolled. The median (range) mGFR and eGFR calculated using the updated Schwartz equation were 118 (43-241) and 135 (34-257) mL/min/1.73 m², respectively. The bias, precision (root mean square error [RMSE]), and accuracy (P30, mGFR±30%) of three eGFR equations including updated Schwartz, 1B, and full age spectrum (FAS) were compared. The median bias (mL/min/1.73 m²) was: updated Schwartz, 8.5; 1B, -9.0; and FAS, 4.2. The biases for all three eGFR equations were significantly different from zero. The P30 was: updated Schwartz, 63.5%; 1B, 66.0%; and FAS, 66.0%. The RMSE was the lowest for the 1B equation (40.4), followed by FAS (42.3), and updated Schwartz (45.5). The median eGFR/mGFR ratio for the eGFR equations decreased with age and reduced kidney functions (i.e., increased creatinine and BUN concentrations). The bias may be further reduced by using the average from two equations, such as the updated Schwartz and 1B, or FAS equation, rather than using the updated Schwartz or 1B equation alone. The use of the 1B equation may underestimate the GFR. Using creatinine and BUN variables in the eGFR equation may yield a more accurate estimate of the GFR in pediatric cancer patients.

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.

Efficient reporting of the estimated glomerular filtration rate without height in pediatric patients with cancer.

BACKGROUND: The updated bedside Schwartz equation requires constant, serum creatinine concentration and height measurements to calculate the estimated glomerular filtration rate (eGFR) in pediatric patients. Unlike the serum creatinine levels, obtaining height information from the laboratory information system (LIS) is not always possible in a clinical laboratory. Recently, the height-independent eGFR equation, the full age spectrum (FAS) equation, has been introduced. We evaluated the performance of height-independent eGFR equation in Korean children with cancer. METHODS: A total of 250 children who underwent chromium-51-ethylenediamine tetra acetic-acid (51Cr-EDTA)-based glomerular filtration rate (GFR) measurements were enrolled. The 51Cr-EDTA GFR was used as the reference GFR. The bias (eGFR - measured GFR), precision (root mean square error [RMSE]) and accuracy (P30) of the FAS equations were compared to those of the updated Schwartz equation. P30 was defined as the percentage of patients whose eGFR was within ±30% of the measured GFR. RESULTS: The FAS equation showed significantly lower bias (mL/min/1.73 m2) than the updated Schwartz equation (4.2 vs. 8.7, p<0.001). The RMSE and P30 were: updated Schwartz of 43.8 and 64.4%, respectively, and FAS of 42.7 and 66.8%, respectively. CONCLUSIONS: The height-independent eGFR-FAS equation was less biased and as accurate as the updated Schwartz equation in Korean children. The use of the height-independent eGFR equation will allow for efficient reporting of eGFR through the LIS in clinical laboratories.

A new strategy for calculating the risk of ovarian malignancy algorithm (ROMA).

BACKGROUND: Reliable quantitative measurements of HE4 and CA125 levels are required to calculate the risk of ovarian malignancy algorithm (ROMA) value. We suggest a new reporting strategy for interpreting ROMA values based on analytical measurement range (AMR) and qualified-intervals of the HE4 and CA125 results. METHODS: HE4 and CA125 assays from Abbott and Roche were used. The AMRs and the qualified-intervals were as follows: Architect HE4 assay, 20-1500 and 17.2-2637.8 pmol/L; Architect CA125 II assay, 1-1000 and 3.9-14,163.0 U/mL; Elecsys HE4 assay, 15-1500 and 28.8-3847 pmol/L; Elecsys CA125 II assay, 0.6-5000 and 6.5-5000 U/mL. These values were used to simulate the ROMA values. RESULTS: Reporting algorithm for the ROMA value could be classified into three categories. (1) If quantitative HE4 and CA125 levels are reliable, the numerical ROMA value can be reported. (2) If HE4 value is <20 and <28.8 for Abbott and Roche in premenopausal woman, the ROMA value should be reported as "low risk" regardless of the CA125 result. In postmenopausal woman, however, it should be reported as "low risk" (CA125<203.0 and <165.8 for Abbott and Roche) or "undetermined" (vice-versa value). (3) If CA125 value is <3.9 and <6.5 for Abbott and Roche, it should be reported as "low risk" (premenopausal HE4<51.5 and <62.2, postmenopausal HE4<323.0 and <281.5 for Abbott and Roche) or "undetermined" (vice-versa value). CONCLUSIONS: New reporting strategy will provide more informative reporting of ROMA values in clinical practice.

Large-scale performance evaluation of Accu-Chek inform II point-of-care glucose meters.

BACKGROUND: The aim of this study was to report the experience of large-scale performance evaluation of 238 Accu-Chek Inform II point-of-care (POC) glucose meters in a single medical setting. METHODS: The repeatability of 238 POC devices, the within-site imprecision of 12 devices, and the linearity of 49 devices were evaluated using glucose control solutions. The glucose results of 24 POC devices and central laboratory were compared using patient samples. RESULTS: Mean concentration of control solutions was 2.39 mmol/L for Level 1 and 16.52 mmol/L for Level 2. The pooled repeatability coefficient of variation (CV) of the 238 devices was 2.0% for Level 1 and 1.6% for Level 2. The pooled within-site imprecision CV and reproducibility CV of the 12 devices were 2.7% and 2.7% for Level 1, and 1.9%, and 1.9% for Level 2, respectively. The test results of all 49 devices were linear within analytical measurement range from 1.55-31.02 mmol/L. The correlation coefficient for individual POC devices ranged from 0.9967-0.9985. The total correlation coefficient for the 24 devices was 0.998. CONCLUSIONS: The Accu-Chek Inform II POC blood glucose meters performed well in terms of precision, linearity, and correlation evaluations. Consensus guidelines for the large-scale performance evaluations of POC devices are required.

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.

Clinical usefulness of bronchoalveolar lavage cellular analysis and lymphocyte subsets in diffuse interstitial lung diseases.

BACKGROUND: Diffuse interstitial lung diseases (DILDs) form a part of a heterogeneous group of respiratory diseases. Bronchoalveolar lavage (BAL) analysis has been used for differential diagnosis of DILDs, but their clinical usefulness is controversial. The aim of this study was to investigate the clinical usefulness of BAL cellular analysis with lymphocyte subsets for the differential diagnosis of DILDs. METHODS: A total of 69 patients diagnosed with DILDs were enrolled. Basic demographic data, BAL cellular analysis with lymphocyte subsets, histology, and high resolution computed tomogram (HRCT) findings were analyzed and compared as per disease subgroup. RESULTS: Significant differences were found between groups in the proportion of neutrophils (P=0.0178), eosinophils (P=0.0003), T cells (P=0.0305), CD4 cells (P=0.0002), CD8 cells (P<0.0001), and CD4/CD8 ratio (P<0.0001). These findings were characteristic features of eosinophilic pneumonia and sarcoidosis. Other parameters were not significantly different between groups. At the cut-off value of 2.16 for sarcoidosis, CD4/CD8 ratio showed sensitivity of 91.7% (95% CI, 61.5-98.6%) and specificity of 84.2% (95% CI, 72.1-92.5%). CONCLUSIONS: Routine analysis of BAL lymphocyte subset may not provide any additional benefit for differential diagnosis of DILDs, except for conditions where BAL is specifically indicated, such as eosinophilic pneumonia or sarcoidosis.

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.

A case of IgM deficiency with B cell deficiency detected by ABO discrepancy in a patient with acute osteomyelitis.

ABO discrepancy refers to an inconsistency between red cell and serum typings and has various causes, including hypogammaglobulinemia. IgM deficiency is a rare disorder that may accompany several conditions such as infection and autoimmune disorders. Here, we describe a case of IgM deficiency discovered during the evaluation of an ABO discrepancy in a 16-yr-old Korean boy. ABO blood grouping showed that while his cell type was O+, serum typing detected only anti-A (3+). Anti-B was not detectable at room temperature but was graded at 1+ at 4℃. ABO genotyping revealed an O/O genotype. His serum IgG, IgA, and IgM concentrations were 770 mg/dL (reference range: 800-1,700 mg/dL), 244 mg/dL (reference range: 100-490 mg/dL), and 13.5 mg/dL (reference range: 50-320 mg/dL), respectively. He was diagnosed with acute osteomyelitis on the basis of clinical presentation and imaging studies. The symptoms gradually improved within 3 weeks of treatment. However, the ABO discrepancy and IgM deficiency persisted even 6 months after recovery and lymphocyte subset analysis revealed CD19+ B cell deficiency. To the best of our knowledge, IgM deficiency detected by ABO discrepancy in a patient with acute osteomyelitis has not been reported before.

[Comparison of HbA1c analyzers: D-10, Variant II Turbo, Cobas Integra 800, and Afinion AS100].

BACKGROUND: The purpose of this study was to evaluate the performance and agreement among HbA(1c) values measured using selected analyzers certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). METHODS: HbA(1c) determined using D-10 (Bio-Rad, USA), Variant II Turbo (Turbo; Bio-Rad, USA), Cobas Integra 800 (Integra; Roche, Switzerland) and Afinion AS100 (Afinion; Axis-Shield, Norway) were compared with each other. Precision and method comparisons with Deming regression were evaluated according to CLSI recommendations. We also compared the HbA(1c) values obtained with each analyzer using either IFCC or NGSP methods by correlation analysis and kappa statistics. RESULTS: The repeatability and method/device precisions of D-10 and Afinion were acceptable. The correlation coefficients of HbA(1c) were 0.986 for D-10 vs. Afinion, 0.997 for D-10 vs. Turbo, 0.988 for D-10 vs. Integra, and 0.991 for Integra vs. Afinion. The average biases of HbA(1c) Afinion (IFCC) and HbA(1c) Integra (IFCC) against HbA(1c) D-10 (NGSP) were -1.90% and -1.79%, respectively. Kappa agreement statistics for the three diabetic control group HbA(1c) values of "less than 6.5%," "6.5%-7.5%," and "greater than 7.5%" for D-10 vs. Turbo, D-10 vs. Integra, and D-10 vs. Afinion were 0.872, 0.836, and 0.833, respectively. CONCLUSIONS: The strong correlations and good clinical agreements of HbA(1c) between each analyzer expressed in terms of either NGSP or IFCC-derived NGSP indicate that these analyzers can be used interchangeably.

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.

[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.

[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.

Prevalence of fat embolism after total knee arthroplasty performed with or without computer navigation.

BACKGROUND: Total knee arthroplasty performed with computer-assisted navigation without breaching of the femoral medullary canal may decrease the prevalence of fat and/or bone-marrow-cell embolization. We performed this study to determine whether the use of navigation for primary total knee arthroplasty resulted in a different prevalence of fat and/or bone-marrow-cell embolization. METHODS: We enrolled 160 patients (210 knees) who were scheduled to undergo primary total knee arthroplasty with navigation and 160 patients (210 knees) who were scheduled to undergo primary total knee arthroplasty without navigation. Arterial and right atrial blood samples were obtained before insertion of a femoral alignment rod or cutting of the distal part of the femur (baseline); at one, three, five, and ten minutes after insertion of an alignment rod or cutting of the distal part of the femur; before insertion of a tibial component broach (baseline); at one, three, five, and ten minutes after insertion of a tibial component broach; and at twenty-four and forty-eight hours after the operation. We determined the presence of fat emboli and bone-marrow-cell emboli in histologic preparations of the blood samples. RESULTS: The prevalence of fat embolization was 49% (102 of 210 knees) in the total knee arthroplasty group managed with navigation and 52% (109 of 210 knees) in the total knee arthroplasty group managed without navigation (p = 0.2674). The prevalence of bone-marrow-cell embolization was 17% (thirty-six of 210 knees) in the group managed with navigation and 15% (thirty-one of 210 knees) in the group managed without navigation (p = 0.2591) CONCLUSIONS: The prevalence of fat and/or bone-marrow-cell embolization was not significantly different between the patients who underwent total knee arthroplasty with navigation and those who underwent it without navigation.

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

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.

hTERT mRNA levels by real-time RT-PCR in acute myelogenous leukemia.

The purpose of this study was to investigate whether levels of hTERT mRNA, as determined by real-time RT-PCR, are associated with prognosis and clinical course in AML patients. Fifty-four bone marrow specimens from 21 patients diagnosed with de-novo AML were included. The level of hTERT mRNA was measured with the Telo TAGGG hTERT Quantification Kit (Roche Diagnostics, Mannheim, Germany), using a LightCycler Instrument (Roche Diagnostics). The level of hTERT mRNA was determined as the relative ratio (RR), which was calculated by dividing the level of hTERT mRNA by the level of the porphobilinogen deaminase (PBGD) housekeeping gene in the same samples [1,000x(hTERT/PBGD)]. The expression rates of hTERT mRNA were significantly higher at diagnosis (73%) and during relapse (80%) than during remission (27%) (P<0.05). The median RR for diagnosis or relapse was significantly higher than that for patients in remission (P<0.05). hTERT mRNA expression was not correlated with CD34 expression, blast counts, white blood cell counts, or chromosomal abnormality (P>0.05). Two patients who showed hTERT mRNA expression during remission (RR 3.14 and 7.15, respectively) relapsed after 1 month. Among seven patients with high hTERT mRNA levels (RR>9.51), 4 failed to achieve complete remission (CR), whereas 4 of 5 patients without hTERT mRNA expression at diagnosis or during relapse achieved CR (P>0.05). Patients showing a trend of increasing hTERT mRNA levels failed to reach a second CR after relapse, while those with a trend toward decreasing hTERT mRNA did achieve CR. Among eight samples showing hTERT mRNA expression in remission (RR>0), 5 were obtained from patients who had received GCSF within 14 days. The expression rate and level of hTERT mRNA during remission were significantly higher in patients who had previously received GSCF (56%, RR=0.15) than in other patients (15%, RR=0) (P<0.05). Serial and quantitative analysis of hTERT mRNA may be a useful marker for prediction of prognosis and monitoring in AML patients.