Clinical Chemistry and Laboratory Medicine (CCLM)

Published by De Gruyter

Volume 50 Issue 10

Issue of Clinical Chemistry and Laboratory Medicine (CCLM)

Contents
Journal Overview

Masthead

Publicly Available October 10, 2012

Masthead

Page range: i-iv

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Editorials

October 10, 2012

Cancer epigenomics: moving slowly, but at a steady pace from laboratory bench to clinical practice

Bohuslav Melichar, Christos Kroupis

Page range: 1699-1701

October 10, 2012

Laboratory networking and sample quality: a still relevant issue for patient safety

Giuseppe Lippi, Ana-Maria Simundic

Page range: 1703-1705

Reviews

April 28, 2012

DNA methylation biomarkers and their utility for solid cancer diagnostics

Karen A. Heichman, Jorja D. Warren

Page range: 1707-1721

Abstract

Cellular DNA undergoes profound changes in methylation during cancer development, with hypermethylation occurring in specific gene promoters, amidst a backdrop of generalized hypomethylation. DNA methylation in cancer often causes the silencing of tumor suppressors and other genes important for cellular growth, regulation and differentiation. Over the past two decades, there have been thousands of publications describing the methylation status of hundreds of genes in cancer, with numerous associations with clinical states, disease outcomes and therapeutic responses being reported. New methods for DNA methylation fingerprinting have emerged, allowing for the exponential growth of “epigenomic” information. Despite this wealth of data, only a handful of methylated genes are utilized as cancer biomarkers in the clinical laboratory. A literature review centered on DNA methylation in six solid cancers was performed, including colorectal, pancreatic, prostate, bladder, breast and ovarian. Commonly methylated genes in the six cancer types were identified and catalogued, and could serve in the future as tissue-based biomarkers or as part of cancer-specific panels. Perhaps more importantly, this endeavor has also focused on methylated genes that appear to be unique to particular cancers. These genes may be more versatile for clinical use, with blood or urine-based cancer screening becoming a reality.

July 12, 2012

DNA methylation biomarkers in biological fluids for early detection of respiratory tract cancer

Soultana Markopoulou, Georgios Nikolaidis, Triantafillos Liloglou

Page range: 1723-1731

Abstract

Cancers of the respiratory tract (lung and head and neck) share common aetiologies, risk factors and molecular characteristics. Epigenetic reprogramming is one of the hallmarks of cancer and DNA methylation is currently the best-studied form. There are a number of characteristics of DNA methylation, which seem advantageous in biomarker development. Early detection is still an unmet clinical care need, which guarantees to significantly reduce the mortality of patients with respiratory cancers. The application of such biomarkers in biological fluids being sampled in everyday clinical practice is a long-term demand. In this review we summarise the current literature on DNA methylation detection in bronchial washings, sputum, saliva, plasma and serum and discuss the potential of their clinical implementation. We also discuss important aspects of biomarker development and validation pointing to the appropriate route for a biomarker to reach clinical standards.

Publicly Available July 15, 2012

Global DNA hypomethylation in cancer: review of validated methods and clinical significance

Estela G. Toraño, Sandra Petrus, Agustin F. Fernandez, Mario F. Fraga

Page range: 1733-1742

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Abstract

DNA methylation is one of the best-known epigenetic modifications in mammals. The alteration of DNA methylation patterns has been found to be related to many diseases, including cancer. It is well-known that during carcinogenesis, a site-specific DNA hypermethylation and a global DNA hypomethylation take place. This overall loss of DNA methylation has been proposed as a valid biomarker for cancer. Given its medical utility, in recent years it has become apparent that there is a need to develop methods for the analysis of DNA methylation using different approaches: global, locus-specific, or genome-wide. Here we review some of these techniques and discuss their potential clinical utility.

Genetics and Molecular Diagnostics

April 20, 2012

δ⁰-Thalassemia in cis of β^Knossos globin gene: first homozygous description in thalassemia intermedia Libyans and first combination with codon 39 (C→T) in thalassemia intermedia Tunisian patients

Chaima Abdelhafidh Sahli, Amina Bibi, Faida Ouali, Hajer Siala, Sondess Hadj Fredj, Rym Othmani, Fekria Ouenniche, Mondher Cheour, Zohra Fitouri, Saida Ben Becher, Taieb Messaoud

Page range: 1743-1748

Abstract

Background: β-Thalassemia is the most common disease among hemoglobinopathies in North African and Arab populations. In the present study we report the first description of the β-Knossos codon27 (G→T) ( β Knossos ) allele in cis with the δ 0 59 (-A) mutation in thalassemia intermedia patients in Tunisia and Libya. Methods: This identification was carried out by sequencing analysis of the whole coding regions of the δ- and β-globin genes. Results: We noted that heterozygous inheritance of the β Knossos mutation results in a mild β-thalassemia phenotype with a low level of HbA 2 while homozygous leads to intermediate β-thalassemia with an atypical high performance liquid chromatogram showing a complete absence of HbA 2 and HbF. Compound heterozygosity of the β Knossos with β 0 codon39 (C→T) is identified in a Tunisian proband for the first time and gives rise to a mild phenotype. In both families, the δ 0 codon59 (-A) and the β Knossos alleles were found to be associated with a single Mediterranean β -haplotype I similar to that observed in previous reports from Algeria, Egypt, Cyprus, and Turkey. Conclusions: The chromosome supporting the β Knossos and the δ 0 codon59 (-A) alleles seems to be of a single Mediterranean origin. Premarital screening studies in families in which only one of the parents has typical aspects of β-thalassemia trait and the other has a normal HbA 2 level associated with abnormal red cell indices becomes a necessity to avoid missing thalassemia carriers.

May 3, 2012

Genetic-based reference values for angiotensin-converting enzyme (ACE) according to I/D polymorphism in a Spanish population sample

Silvia Camós, M. Jesús Cruz, Ferran Morell, Esther Solé

Page range: 1749-1753

Abstract

Background: Serum angiotensin-converting enzyme (ACE) activity has been related to sarcoidosis and other granulomatous diseases. It has been demonstrated that serum ACE activity is influenced by ACE gene I/D polymorphism. The aim of this study was to establish ACE activity reference values according to genotype in a Spanish population to improve diagnostic sensitivity and treatment monitoring in sarcoidosis patients. Methods: A sample population of 150 blood donors was included in the study. Serum ACE activity and genotype were determined and the reference intervals, defined as the 95% central range of the population (2.5th–97.5th percentiles) were obtained for all three genotypes ( DD, DI, II ) and for the entire sample. Results: Genotype frequencies were 37% DD (n=54), 43% DI (n=63), and 20% II (n=30). Individuals with DD genotype showed the highest ACE activity (mean 39.0 U/L, SD 13.6), ID genotype showed intermediate levels (mean 29.5 U/L, SD 10.2) and II genotype lowest levels (mean 19.1 U/L, SD 4.9). ACE activity differed significantly between these groups: F (2144)=33.15, p<0.05. The corresponding reference intervals for ACE activity were 13.3–63.9 U/L in the overall sample, 12.3–65.6 U/L in genotype DD , 9.5–49.5 U/L in DI and 9.6–28.7 in II . Conclusions: The preliminary reference values for ACE activity in healthy Spanish individuals according to I/D polymorphism are presented. Significant differences in these values were found between the genotype groups.

General Clinical Chemistry and Laboratory Medicine

Publicly Available May 4, 2012

Effects of sample transportation on commonly requested laboratory tests

Martina Zaninotto, Adriano Tasinato, Andrea Padoan, Gianni Vecchiato, Alessio Pinato, Laura Sciacovelli, Mario Plebani

Page range: 1755-1760

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Abstract

Background: Little evidence is available in literature on the effects of sample transportation. The aim of the present study was to evaluate the effects of an integrated system for sample transportation on the quality of six laboratory parameters considered representative of the quality of all tests requested and performed. Methods: The values of alanine aminotransferase (ALT), calcium (Ca), potassium (K), activated prothrombin time (APTT), prostate specific antigen (PSA), and hemoglobin (Hb) obtained in samples collected in peripheral centers in 2007 were compared with those obtained in 2011, following the introduction of the integrated transportation system entailing a tertiary and a secondary container, a data-logger for registering time and temperature, a mission starter and a system manager. Results: In 2007, for ALT, APTT and K, there were significant variations between findings for samples transported from long-term and those from short-term peripheral centers; following the introduction of the transportation system, no such variations were found. Conclusions: Improvement in the quality of sample transportation has been achieved, particularly for three of the six parameters evaluated, following the introduction of the integrated system described in the present study.

April 16, 2012

Long-term (in)stability of folate and vitamin B₁₂ in human serum

Eugène H.J.M. Jansen, Piet K. Beekhof, Johannes W.J.M. Cremers, Erna Schenk

Page range: 1761-1763

Abstract

Background: In epidemiological research it is very important to test the stability of biomarkers as a function of both storage time and temperature. In this study the stability of both folate and vitamin B 12 in human serum samples have been tested after storage at three different temperatures up to 1 year. Methods: Serum samples of 16 individuals were used in this study. The concentration of folate and vitamin B 12 has been determined at T=0 and at several time points up to 1 year after storage at –20°C, –70°C and –196°C. The statistical difference from the initial value at T=0 were determined with a t-test. Results: Folate in serum samples remained stable at –70°C but was not stable during storage at –20°C. A fast decrease was observed after Day 4 which resulted in a stable level of about 60% of the original value measured at T=0 (p<0.001). The rank order of folate concentration in the samples, however, was not affected. The stability of vitamin B 12 was good at all temperatures tested. Conclusions: Measurements of folate concentrations in serum stored at –20°C are not reliable. The rank order, however, was not changed. Vitamin B 12 was stable at all temperatures tested. For both folate and vitamin B 12 storage at –70°C is sufficient to maintain the original concentration for 1 year. Storage at –196°C in liquid nitrogen is not necessary for these nutrients.

May 11, 2012

Information comparison of the effects of drugs on laboratory tests in drug labels and Young’s book

Arjen F.J. Geerts, Fred H.P. De Koning, Toine C.G. Egberts, Peter A.G.M. De Smet, Wouter W. Van Solinge

Page range: 1765-1768

Abstract

Background: The effects of drugs on laboratory tests may lead to misinterpretation of laboratory data, unnecessary tests, higher costs and missed diagnoses. This study compared the information on drug-laboratory effects (DLE) described in 200 drug labels with that in Young’s book. Methods: Information on DLE was searched in the drug labels of 200 frequently prescribed drugs using the keywords ‘interfer*’, ‘influence’, and ‘laborator*’. This information was compared with the information in Young’s book. Each item of information scored 1 point if it was specific and exactly the same. Primary outcome was the percentage of DLE with completely the same information. Results: In 23 (11.5%) of the 200 drug labels 83 DLE were described. Most DLE were described in drug labels of contraceptives (71%) and antibacterials (15%). The most frequently affected laboratory tests were adrenal gland (17%), urine tests (15%), liver tests (10%) and renal function tests (10%). Comparison of six DLE with Young’s book was not possible because the information was not described in the book. Twelve (14.5%) DLE of the information in the drug label was identical to that in Young’s book. Detailed information about nature of the effect, strength of the effect and body fluid was not described in the drug labels. Conclusions: In a limited number of DLE in the drug labels the information was the same as in Young’s book. Overall, the information on DLE provided in drug labels is unclear, inconsistent and incomplete and does not support healthcare professionals in making evidence-based monitoring decisions.

April 26, 2012

First evaluation of Capillarys 2 Flex Piercing^® (Sebia) as a new analyzer for HbA_1c assay by capillary electrophoresis

Stéphane Jaisson, Nathalie Leroy, Julie Meurice, Emmanuelle Guillard, Philippe Gillery

Page range: 1769-1775

Abstract

Background: HbA 1c is a key biomarker for the monitoring of glycemic balance in diabetic patients. It may be measured by various methods, including HPLC and immunoassays. Here we report the results of the first evaluation of Capillarys 2 Flex Piercing ® , a new analyzer using capillary electrophoresis for the separation and the quantification of HbA 1c . Methods: We have evaluated the analytical performances of the method as well as the influence of the most frequent analytical interferences regarding HbA 1c assays (i.e., labile HbA 1c , carbamylated hemoglobin, high HbF and hemoglobin variants). Results: Intra-assay and between-assays CVs were respectively lower than 1.98% and 2.68% on the pre-market version of the instrument, and lower than 1.62% and 1.45% on the commercial version. The linearity was excellent for HbA 1c values ranging from 19 mmol/mol (3.9%) to 161 mmol/mol (16.9%) (r=0.999). The results were well correlated with those obtained by the HPLC method routinely used in the laboratory (Variant II ® NU Kit – Bio-Rad): HbA 1c [Capillarys 2]=0.9452×HbA 1c [Variant II]+1.7279 (r=0.994, n=500). The use of titrated quality control samples indicated a good accuracy of the method. Neither the presence of HbF (until 15%), labile HbA 1c or carbamylated hemoglobin, nor that of some typical hemoglobin variants, such as hemoglobin S, D, C and E, affected HbA 1c measurement. Conclusions: This evaluation showed that the analytical performances of Capillarys 2 Flex Piercing ® analyzer for HbA 1c assay fulfilled quality criteria requested for clinical use, and allowed to recommend its implementation in clinical chemistry laboratories for routine practice.

April 26, 2012

Antioxidant and oligonutrient status, distribution of amino acids, muscle damage, inflammation, and evaluation of renal function in elite rugby players

Anne Marie Gorce-Dupuy, Carlos Vela, Stéphanie Badiou, Anne Sophie Bargnoux, Christophe Josse, Nicolas Roagna, Martine Delage, Françoise Michel, Marie Hélène Vernet, Dominique Destizons, Jean Paul Cristol

Page range: 1777-1789

Abstract

Background: Our study investigated the biochemical and anthropometric characteristics in elite athletes of rugby union based in the south of France during the different periods of the competition to identify metabolic and biochemical adaptations to particular lifestyle conditions. Methods: Participants included 35 players in 2008 and 43 players in 2009. Biochemical variables [creatinine, uric acid, creatine kinase (CK), alanine aminotransferase, aspartate aminotransferase, C-reactive protein] were evaluated. Specific protein levels (albumin, acid α-glycoprotein, prealbumin), vitamins (A, E, C), antioxidant enzymes [glutathione peroxidase (GPx), superoxide dismutase (SOD)], oligoelements (Zn, Se, Cu, erythrocyte magnesium), homocysteine (Hcy), carnitine and the distribution of amino acids were specifically determined for our study during a pre-competition period (September 2008 and 2009). Results: Globally, no deficit was observed for vitamins, oligonutrients and amino acids levels. The high SOD and GPx activities in rugby players suggest a presence of oxidative stress of exercise. The evaluation of renal function should be used with caution because of the interaction between creatinine and lean body mass. In addition, a profound effect of intense exercise on the CK values was reported to establish specific reference values for athletes. The analysis of the biological variation allows optimization of the interpretation of the changes from an increased or decreased baseline value from a season to the other one. Conclusions: The conclusions of present study were: 1) the necessity of rugby-specific reference intervals for CK and creatinine parameters; 2) the use of enzymatic creatinine for Modification of Diet in Renal Disease (MDRD) and CKD-EPI, or cystatin C to improve glomerular filtration rate estimation; 3) to take into account the oxidative stress testifying of a bad recovery; and 4) better to take care the nutritional status of the players by adapting needs and amino acids supplementations but also to consider a follow-up of oxidative stress and antioxidants according our results.

May 7, 2012

Validation of the body fluid module on the new Sysmex XN-1000 for counting blood cells in cerebrospinal fluid and other body fluids

Chérina Fleming, Rob Brouwer, Jan Lindemans, Robert de Jonge

Page range: 1791-1798

Abstract

Background: We evaluated the body fluid (BF) module on the new Sysmex XN-1000 for counting blood cells. Methods: One hundred and eighty-seven BF samples [73 cerebrospinal fluid (CSF), 48 continuous ambulatory peritoneal dialysis (CAPD), 46 ascites, and 20 pleural fluid] were used for method comparison between the XN-1000 and manual microscopy (Fuchs-Rosenthal chamber and stained cytospin slides) for counting red blood cells (RBCs) and white blood cells (WBCs) (differential). Results: Good agreement was found for counting WBCs (y=1.06x + 0.09, n=67, R 2 =0.96) and mononuclear cells (MNs) (y=1.04x–0.01, n=40, R 2 =0.93) in CSF. However, the XN-1000 systematically counted more polymorphonuclear cells (PMNs) (y=1.48x + 0.18, n=40, R 2 =0.99) compared to manual microscopy. Excellent correlation for RBCs >1×10 9 /L (y=0.99x + 116.56, n=26, R 2 =0.99) in CSF was found. For other fluids (CAPD, ascites and pleural fluid) excellent agreement was found for counting WBCs (y=1.06x + 0.26, n=109, R 2 =0.98), MNs (y=1.06x–0.41, n=93, R 2 =0.96), PMNs (y=1.06x + 0.81, n=93, R 2 =0.98) and RBCs (y=1.04x + 110.04, n=43, R 2 =0.98). By using BF XN-check, the lower limit of quantitation (LLoQ) for WBC was defined at 5×10 6 /L. Linearity was excellent for both the WBCs (R 2 =0.99) and RBCs (R 2 =0.99) and carry-over never exceeded 0.05%. Conclusions: The BF module on the XN-1000 is a suitable tool for fast and accurate quantification of WBC (differential) and RBC counts in CSF and other BFs in a diagnostic setting.

March 30, 2012

Measuring Rivaroxaban in a clinical laboratory setting, using common coagulation assays, Xa inhibition and thrombin generation

Pascal J. Molenaar, Jasper Dinkelaar, Anja Leyte

Page range: 1799-1807

Abstract

Background: Rivaroxaban, a direct Xa inhibitor, is one of the new oral antithrombotic agents for which laboratory monitoring is thought to be unnecessary in most cases due to predictable pharmacokinetics. Circumstances are conceivable, however, in which reliable laboratory testing of Rivaroxaban is desirable. The aim of the present in vitro study was to investigate and compare the analytical and practical use of Rivaroxaban monitoring with routine screening assays, thrombin generation and anti-Xa activity, in a clinical laboratory setting. Methods: Rivaroxaban was added to nine normal donor plasmas and to a normal pooled plasma in concentrations up to 1000 μg/L. Prothrombin time (PT), activated partial thromboplastin time (APTT), endogenous thrombin potential (ETP) and anti-Xa activity were measured in all donor samples. Responsiveness to Rivaroxaban and imprecision of Rivaroxaban recovery were assessed. Results: Low intra-, but high inter-individual imprecision was found for PT displaying a linear dose-response relationship. Imprecision was much lower when directly measuring anti-Xa activity. Responsiveness of ETP lag-time was high, but of total thrombin generation was low, illustrating that the main effect of Rivaroxaban Xa inhibition lies in delaying thrombin formation rather than in preventing it. Conclusions: Despite a high inter-individual imprecision of the PT, this relatively fast and cost-friendly assay is sensitive to Rivaroxaban and integrates its effects on the global coagulant state of patients. Anti-Xa activity assays can be run to assess the actual Rivaroxaban concentration and in the future ETP could serve as a fine-tuned hemostatic balance indicator for patients using Rivaroxaban.

Cancer Diagnostics

May 10, 2012

Increased concentrations of growth factors and activation of the EGFR system in breast cancer

Dorte Aa. Olsen, Troels Bechmann, Birthe Østergaard, Peter A. Wamberg, Erik H. Jakobsen, Ivan Brandslund

Page range: 1809-1818

Abstract

Background: In this study the total and phosphorylated amount of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) were measured together with EGFR ligands in tissue samples of breast cancer patients in order to investigate interrelations and possible prognostic values. Methods: Samples of malignant and non-cancer autologous reference tissue were collected from 415 breast cancer patients. The tissue samples were cut and either paraffin-embedded or homogenized in a lysis buffer to extract the proteins. HER2 was measured using both immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) and ADVIA Centaur. Phosphorylated HER2 and EGFR (pHER2, pEGFR), total EGFR and the ligands: epidermal growth factor (EGF), transforming growth factor-α (TGFα), amphiregulin (AREG), heparin-binding EGF-like growth factor (HB-EGF), betacellulin (BTC) and epiregulin (EREG) were measured using the Luminex. Results: The HER2 positivity rate was determined to be 25.2% by the Centaur method vs. 15.8% by IHC and FISH. HER2, HB-EGF, TGFα and AREG were upregulated in cancer tissue as compared with autologous reference tissue while EGFR, pEGFR and EGF were downregulated (p<10 –6 ). pEGFR in autologous reference tissue was negatively correlated to the number of positive lymph nodes and to the tumor size (p=0.0007 and p=0.001, respectively) and furthermore, decreased in the group of mastectomy operated patients as compared with the lumpectomy group (p<10 –6 ). HB-EGF in cancer tissue was positively associated with high grade tumors (p<10 –6 ) and pHER2, HB-EGF and BTC were associated with poor disease free survival (p=0.017, p=0.012 and p=0.0026, respectively). Conclusions: Our study demonstrated a profound activation of the EGFR system. HB-EGF was increased by factor 10 in cancer tissue and related to the biological aggressiveness of the tumors, and pHER2, HB-EGF and BTC were associated with poor clinical outcome.

Infectious Diseases

May 10, 2012

Incidence and significance of elevated lactate in the identification of critically ill patients

Seth H. Sheldon, Amy K. Saenger, Allan S. Jaffe

Page range: 1819-1823

Abstract

Background: The frequency and characteristics of patients with critical lactate values (>4.0 mmol/L) is unknown. Methods: The laboratory database was reviewed for adult patients with non-point of care lactate values over a 6-month period. Results: There were 6914 lactate values, including 625 (9.0%) critical values. Medical records were reviewed in 100 patients with critical and non-critical lactate values. Patients with critical vs. non-critical values had more metabolic acidosis (n=70/100 vs. 22/100, p<0.01), hypotension or tachycardia (n=62/100 vs. 29/100, p<0.01), and a higher 1-month mortality (n=42/100 vs. 7/100, p<0.01). Few patients (n=10/100) with a critical value were not in the emergency department or intensive care unit. Conclusions: Critical lactate values are associated with a longer duration of hospitalization and increased mortality. However, the incremental value of critical lactate values was low, as most patients had abnormal vital signs and laboratory parameters. Requiring notification of lactate values >4.0 mmol/L would be unlikely to augment clinical care.

Cardiovascular Diseases

April 28, 2012

Lipoprotein-associated phospholipase A₂ is elevated in patients with severe aortic valve stenosis without clinically overt atherosclerosis

Renata Kolasa-Trela, Korneliusz Fil, Marta Bazanek, Grzegorz Grudzień, Dorota Sobczyk, Jerzy Sadowski, Anetta Undas

Page range: 1825-1831

Abstract

Background: Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is an inflammatory mediator involved in atherosclerosis. Since aortic valve stenosis (AVS) is regarded as an atherosclerosis-like inflammatory disease, we sought to investigate whether AVS is associated with elevated Lp-PLA 2 . Methods: Plasma Lp-PLA 2 levels were determined in 48 consecutive patients with severe AVS without atherosclerotic vascular disease and compared with the values obtained in 48 controls matched for age, sex and cardiovascular risk factors. Results: Lp-PLA 2 was higher in AVS than in controls (242.3±50.4 vs. 151.9±28.1 ng/mL, p<0.0001). Lp-PLA 2 correlated inversely with aortic valve area (AVA) (r=–0.53; p=0.0001) and positively with mean pressure gradient (PG) (r=0.32; p=0.029). In multivariable analysis C-reactive protein (CRP) (OR=1.42; 95% CI 0.95–2.1; p=0.09) and AVA (OR=0.003; 95% CI 0.00004–0.23; p<0.01) were independently associated with Lp-PLA 2 above a mean of 242 ng/mL. After adjustment for CRP, AVA was the only independent predictor of Lp-PLA 2 in AVS patients (p<0.001). Conclusions: This study is the first to show that AVS is characterized by increased plasma Lp-PLA 2 levels associated with the severity of AVS, which suggests active involvement of Lp-PLA 2 in the pathogenesis of AVS.

Diabetes

May 3, 2012

Serum cystatin C as a marker for early detection of chronic kidney disease and grade 2 nephropathy in Japanese patients with type 2 diabetes

Yoshitake Suzuki, Kazuyuki Matsushita, Masanori Seimiya, Toshihiko Yoshida, Yuji Sawabe, Makoto Ogawa, Fumio Nomura

Page range: 1833-1839

Abstract

Background: Diabetic nephropathy (DN) is a significant cause of hemodialysis, and its early detection is extremely important to prevent or delay end-stage renal disease. The significance of the renal function marker serum cystatin C (sCysC) and its relationship with glomerular filtration rate in chronic kidney disease (CKD) and DN in Japanese patients with type 2 diabetes remains uncertain. In this study, we examined the effectiveness of sCysC as a marker of early DN and CKD in Japanese subjects. Methods: A total of 325 Japanese patients with type 2 diabetes and 88 healthy subjects were studied retrospectively. sCysC concentration (mg/L) was determined by a latex turbidmetric immunoassay using a BioMajesty 8040 analyzer. The renal function of the diabetic patients was evaluated using the albumin-creatinine ratio (ACR) and Kidney Disease Outcome Quality Initiative-Kidney Disease Improving Global Outcomes (K/DOQI-KDIGO) classification. Results: There was a significant increase in sCysC but not in serum creatinine (sCr) or serum β 2 -microglobulin (sβ2M) in patients with grade 2 DN (ACR 30–300 mg/g) compared to grade 1 patients. Receiver operating characteristic analysis in grade 2 and 3 DN patients showed that sCysC had superior sensitivity and specificity than sCr and sβ2M for early detection of DN. In addition, sCysC showed particularly high sensitivity and specificity in DN patients with stage 2 CKD. Conclusions: sCysC was effective for detection of grade 2 DN and would be especially useful for screening stage 2 CKD patients (K/DOQI-KDIGO).

Letters to the Editor

March 30, 2012

Establishing professional phlebotomist group for quality control of the preanalytic variables of clinical laboratory

Haijuan Wang, Xiaojuan Liu, Linghan Kuang, Hua Shi, Yongmei Jiang

Page range: 1841-1842

March 30, 2012

Application of quality specification based on biological variation in planning quality control strategy

Limin Yin, Gang Li, Dachun Hu

Page range: 1843-1844

March 26, 2012

Analytical and clinical evaluation of a new immunoassay for therapeutic drug monitoring of infliximab and adalimumab

Francisca Llinares-Tello, José Rosas-Gómez de Salazar, José Miguel Senabre-Gallego, Gregorio Santos-Soler, Carlos Santos-Ramírez, Esteban Salas-Heredia, Juan Molina-García

Page range: 1845-1847

April 20, 2012

Comparison of relationships between FT4 and log TSH in Access DXI 800 Unicel, Modular E170 and ADVIA Centaur XP Analyzer

Muhittin A. Serdar, Taner Ozgurtas, Emre Ispir, Levent Kenar, Mehmet Senes, Dogan Yücel, Cumhur Bilgi, Ismail Kurt

Page range: 1849-1852

March 30, 2012

Assay-specific pitfalls of catecholamine HPLC assays

Judith A.P. Bons, Bas Havekes, Paul G.A. Volders, Chris de Zwaan, Ido P. Kema, Will K.W.H. Wodzig, Paul P.C.A. Menheere

Page range: 1853-1856

April 23, 2012

Evaluation of automated nucleated red blood cells counting on Sysmex XE5000 and Siemens ADVIA 2120

Silvia Pipitone, Fernanda Pavesi, Beatrice Testa, Mirco Bardi, Giuseppina B. Perri, Daniela Gennari, Giuseppe Lippi

Page range: 1857-1859

May 3, 2012

Evaluation of the immature myeloid information (IMI) by Sysmex XE 2100^® hematology analyzer in the identification of blasts of myeloid lineage

Mariela Granero Farias, Mariana Pires Garcia, Claudia Rosa Cagliari

Page range: 1861-1864

Abstract

The immature myeloid information (IMI) provided by the Sysmex XE 2100 hematology analyzer has demonstrated that it is possible to differentiate granulocytes of immature cells in daily practice. A specific reagent lyses mature white blood cells, allowing that immature myeloid cells remain intact and consequently detectable. It is known that lymphoblasts cannot be detected in this channel. This channel does not entail additional costs, since it is provided by the traditional hematology analyzers used in blood tests and is widely useful in differentiating cell lines. This study has aimed to assess the consonance between IMI results and subtypes of acute leukemias and other hematologic malignancies in order to use it as screening test in the definition of cell lineage. A total of 141 cases of hematologic malignancies have been evaluated. Results of the IMI channel were compared using the Sudan Black cytochemical and flow cytometry. The Cohen’s Kappa coefficient of agreement between IMI and flow cytometry results was 0.8%. IMI had sensibility and specificity levels of 90.7% and 90.8%, respectively; VP: 68 (91.9%); FP: 6 (8.1%); VN: 59 (89.4%) and FN: 7 (10.6%); PPV 91.9% and NPV 89.4%. The Sysmex XE 2100 analyzer showed a good analytical performance for the detection of immature myeloid cells. These results indicate that the IMI channel has sensitivity and specificity levels, consistent with previous studies. Given this situation, one may conclude that IMI was able to be used as a screening test to complement cytochemistry for identify blasts of myeloid lineage.

Congress Abstracts

October 10, 2012

Congress of Laboratory Medicine and Clinical Chemistry / 4th Annual Meeting of the Austrian Society for Laboratory Medicine and Clinical Chemistry (ÖGLMKC)

Page range: A271-A294

October 10, 2012

Abstracts of the 2012 Convocation of Experts on Laboratory Quality / Embracing the Need of Continued Vigilance to Assure Quality Outcomes in the Modern Laboratory

Page range: A295-A305

About this journal

Objective
Clinical Chemistry and Laboratory Medicine (CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. It is focused on basic and applied research and cutting-edge clinical laboratory medicine. CCLM is one of the leading journals in the field, with an impact factor over 3.5. All contributions submitted for publication in CCLM are single-blind peer reviewed by at least two experts in the field. CCLM is led by a multi-institutional editorial board. It is issued monthly, both in print and electronically. Letters to the Editor and Congress Abstracts are published online only.

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Topics

clinical biochemistry
clinical genomics and molecular biology
clinical haematology and coagulation
clinical immunology and autoimmunity
clinical microbiology
drug monitoring and analysis
evaluation of diagnostic biomarkers
disease-oriented topics (cardiovascular disease, cancer diagnostics, diabetes)
new reagents, instrumentation and technologies
new methodologies
reference materials and methods
reference values and decision limits
quality and safety in laboratory medicine
translational laboratory medicine
clinical metrology

Article formats
Research Articles, Reviews, Mini Reviews and Opinion Papers on all aspects of clinical chemistry and laboratory medicine, Guidelines and Recommendations, Point/Counterpoint Articles, Letters to the Editor, Editorials

Volume 50 Issue 10

Issue of Clinical Chemistry and Laboratory Medicine (CCLM)

Masthead

Cancer epigenomics: moving slowly, but at a steady pace from laboratory bench to clinical practice

Laboratory networking and sample quality: a still relevant issue for patient safety

DNA methylation biomarkers and their utility for solid cancer diagnostics

Abstract

DNA methylation biomarkers in biological fluids for early detection of respiratory tract cancer

Abstract

Global DNA hypomethylation in cancer: review of validated methods and clinical significance

Abstract

δ0-Thalassemia in cis of βKnossos globin gene: first homozygous description in thalassemia intermedia Libyans and first combination with codon 39 (C→T) in thalassemia intermedia Tunisian patients

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Genetic-based reference values for angiotensin-converting enzyme (ACE) according to I/D polymorphism in a Spanish population sample

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Effects of sample transportation on commonly requested laboratory tests

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Long-term (in)stability of folate and vitamin B12 in human serum

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Information comparison of the effects of drugs on laboratory tests in drug labels and Young’s book

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First evaluation of Capillarys 2 Flex Piercing® (Sebia) as a new analyzer for HbA1c assay by capillary electrophoresis

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Antioxidant and oligonutrient status, distribution of amino acids, muscle damage, inflammation, and evaluation of renal function in elite rugby players

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Validation of the body fluid module on the new Sysmex XN-1000 for counting blood cells in cerebrospinal fluid and other body fluids

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Measuring Rivaroxaban in a clinical laboratory setting, using common coagulation assays, Xa inhibition and thrombin generation

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Increased concentrations of growth factors and activation of the EGFR system in breast cancer

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Incidence and significance of elevated lactate in the identification of critically ill patients

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Lipoprotein-associated phospholipase A2 is elevated in patients with severe aortic valve stenosis without clinically overt atherosclerosis

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Serum cystatin C as a marker for early detection of chronic kidney disease and grade 2 nephropathy in Japanese patients with type 2 diabetes

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Establishing professional phlebotomist group for quality control of the preanalytic variables of clinical laboratory

Application of quality specification based on biological variation in planning quality control strategy

Analytical and clinical evaluation of a new immunoassay for therapeutic drug monitoring of infliximab and adalimumab

Comparison of relationships between FT4 and log TSH in Access DXI 800 Unicel, Modular E170 and ADVIA Centaur XP Analyzer

Assay-specific pitfalls of catecholamine HPLC assays

Evaluation of automated nucleated red blood cells counting on Sysmex XE5000 and Siemens ADVIA 2120

Evaluation of the immature myeloid information (IMI) by Sysmex XE 2100® hematology analyzer in the identification of blasts of myeloid lineage

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Congress of Laboratory Medicine and Clinical Chemistry / 4th Annual Meeting of the Austrian Society for Laboratory Medicine and Clinical Chemistry (ÖGLMKC)

Abstracts of the 2012 Convocation of Experts on Laboratory Quality / Embracing the Need of Continued Vigilance to Assure Quality Outcomes in the Modern Laboratory

δ⁰-Thalassemia in cis of β^Knossos globin gene: first homozygous description in thalassemia intermedia Libyans and first combination with codon 39 (C→T) in thalassemia intermedia Tunisian patients

Long-term (in)stability of folate and vitamin B₁₂ in human serum

First evaluation of Capillarys 2 Flex Piercing^® (Sebia) as a new analyzer for HbA_1c assay by capillary electrophoresis

Lipoprotein-associated phospholipase A₂ is elevated in patients with severe aortic valve stenosis without clinically overt atherosclerosis

Evaluation of the immature myeloid information (IMI) by Sysmex XE 2100^® hematology analyzer in the identification of blasts of myeloid lineage