Clinica chimica acta; international journal of clinical chemistry

Publications in this journal

• Article: Metabolomics in Noninvasive Breast Cancer.

  Ai-Hua Zhang, Hui Sun, Qiu Shi, Xi-Jun Wang
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  ABSTRACT: Breast cancer remains the most leading cause of death among women worldwide. Common methods for diagnosis and surveillance include mammography, histopathology and blood tests. The major drawback of mammography is the high rate of false reports, aside from the risk from repeated exposure to harmful ionizing radiations; histopathology is time consuming and often prone to subjective interpretations; blood-based tests are attractive, but lack the sensitivity and specificity. Obviously, more sensitive biomarkers for early detection and molecular targets for better treating breast cancer are urgently needed. Fortunately, molecular level 'omics' diagnosis is becoming increasingly popular; metabolomics, diagnosis based on 'metabolic fingerprinting' may provide clinically useful biomarkers applied toward identifying metabolic alterations and has introduced new insights into the pathology of breast cancer. By applying advanced analytical and statistical tools, metabolomics involves the comprehensive profiling of the full complement of low molecular weight compounds in a biological system and could classify the basis of tumor biology of breast cancer, to identify new prognostic and predictive markers and discover new targets for future therapeutic interventions. This advanced bioanalytic methods may now open new avenues for diagnostics in cancer via discovery of biomarkers. In this review we take a closer look at the metabolomics used within the field of breast cancer diagnosis. Further, we highlight the most interesting metabolomics publications and discuss these in detail; additional studies are mentioned as a reference for the interested reader. A general trend is an increased focus on biological interpretation rather than merely the ability to classify samples.
  Clinica chimica acta; international journal of clinical chemistry 05/2013;
• Article: Patient Satisfaction With Point-of-Care Laboratory Testing: Report of a Quality Improvement Program in an Ambulatory Practice of an Academic Medical Center.

  Benjamin Crocker, Elizabeth-Lee Lewandrowski, Nicole Lewandrowski, Kimberly Gregory, Kent Lewandrowski
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  ABSTRACT: BACKGROUND: Point-of-care laboratory testing (POCT) offers reduced turnaround time and may facilitate medical decision-making and improve clinical operations. However, there is very little published data concerning the impact of POCT on patient satisfaction. METHODS: We implemented POCT for hemoglobin A1c, lipid panel and comprehensive metabolic panel in a primary care practice and monitored patient satisfaction with on-site testing using an anonymous survey. RESULTS: A total of 97 surveys (65% response rate) were reviewed. On a scale of 1 (poor) to 4 (excellent) the mean response to the question "Compared with your past experiences of physician office visits that did not have on-site testing please rank your overall level of satisfaction with today's office visit" was 3.96. In 34 surveys a free text comment was included which were uniformly very positive. CONCLUSIONS: Our study strongly indicates a high level of patient satisfaction with on-site POCT in a primary care setting.
  Clinica chimica acta; international journal of clinical chemistry 05/2013;
• Article: Gene methylation in gastric cancer.

  Yiping Qu, Siwen Dang, Peng Hou
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  ABSTRACT: Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes has led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field.
  Clinica chimica acta; international journal of clinical chemistry 05/2013;
• Article: Measurement of Dehydroepiandrosterone sulphate (DHEAS): A comparison of Isotope-Dilution Liquid Chromatography Tandem Mass Spectrometry (ID-LC-MS/MS) and seven currently available immunoassays.

  Rahel M Büttler, Adrian Kruit, Marinus A Blankenstein, Annemieke C Heijboer
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  ABSTRACT: BACKGROUND: Dehydroepiandrosterone sulphate (DHEAS) is an important marker of the adrenal gland. Its measurement is required in several adrenal diseases, such as adrenal tumours, adrenal insufficiency and congenital adrenal hyperplasia. Most clinical laboratories measure DHEAS using commercially available immunoassays. The aim of the present study was to investigate the accuracy of currently available DHEAS methods. METHODS: Seven commercially available DHEAS assays were compared to ID-LC-MS/MS by measuring 75 serum samples (concentration range 0.06- 20.6μmol/L measured by ID-LC-MS/MS) with each method. Moreover, recovery and linearity experiments were performed. Data from our present study were compared to DHEAS data of the Dutch, German and British External Quality Assessment Schemes (EQAS's). RESULTS: Three methods agreed well with ID-LC-MS/MS (R between 0.93 and 0.99 and slopes ranging from 0.92 to 1.07) and showed good recoveries. Four methods showed standardization problems (slopes were 0.84, 1.14, 1.20 and 1.28). Linearity was good in all methods. Intra-assay coefficients of variation was 4.1% using ID-LC-MS/MS and below 5.5% in immunometric methods; one assay had an unacceptably high intra-assay coefficient of variation of 18%. Our data are in agreement with data obtained in three EQAS's. CONCLUSION: Some of the commercially available DHEAS methods show standardization problems and/or a high imprecision. These problems may potentially have clinically adverse consequences. We advise the manufacturers to improve their assays and laboratory specialists to scrutinize the DHEAS method they employ.
  Clinica chimica acta; international journal of clinical chemistry 05/2013;
• Article: Multiplex Newborn Screening for Pompe, Fabry, Hunter, Gaucher, and Hurler Diseases Using a Digital Microfluidic Platform.

  Ramakrishna S Sista, Tong Wang, Ning Wu, Carrie Graham, Allen Eckhardt, Theodore Winger, Vijay Srinivasan, Deeksha Bali, David S Millington, Vamsee K Pamula
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  ABSTRACT: PURPOSE: New therapies for lysosomal storage diseases (LSDs) have generated interest in screening newborns for these conditions. We present performance validation data on a digital microfluidic platform that performs multiplex enzymatic assays for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases. METHODS: We developed an investigational disposable digital microfluidic cartridge that uses a single dried blood spot (DBS) punch for performing a 5-plex fluorometric enzymatic assay on up to 44 DBS samples. Precision and linearity of the assays were determined by analyzing quality control DBS samples; clinical performance was determined by analyzing 600 presumed normal and known affected samples (12 for Pompe, 7 for Fabry and 10 each for Hunter, Gaucher and Hurler). RESULTS: Overall coefficient of variation (CV) values between cartridges, days, instruments, and operators ranged from 2 to 21%; linearity correlation coefficients were ≥ 0.98 for all assays. The multiplex enzymatic assay performed from a single DBS punch was able to discriminate presumed normal from known affected samples for 5 LSDs. CONCLUSIONS: Digital microfluidic technology shows potential for rapid, high-throughput screening for 5 LSDs in a newborn screening laboratory environment. Sample preparation to enzymatic activity on each cartridge is less than 3 hours.
  Clinica chimica acta; international journal of clinical chemistry 05/2013;
• Article: Two cardiac troponin assays not affected by hemolysis - a patient safety issue.

  Renze Bais
  Clinica chimica acta; international journal of clinical chemistry 05/2013;
• Article: Non-transference of biological reference interval of TSH by electrochemiluminescence immunoassay: an Indian population perspective.

  Rajarshi Sarkar
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  ABSTRACT: INTRODUCTION: Although TSH measurement by electrochemiluminescence immunoassay (has become commonplace in India, significant discrepancy has been observed on interpretation of the test results when the manufacturer supplied biological reference interval (BRI) criteria were applied. This report determined whether the manufacturer's BRI (Roche Cobas) is transferable to the Indian population. METHODS: Three hundred seventy-eight age and sex matched healthy subjects were selected from an urban Indian population, TSH reference measurements were acquired and the reference data were statistically analysed. RESULTS: BRI of the Indian urban reference population was determined by non-parametric means. BRI was found to be 1.134μIU/ml to 7.280μIU/ml. CONCLUSION: BRI thus calculated was found to be significantly different from that mentioned by the manufacturer (0.27 to 4.20μIU/ml), which, needless to mention, has profound clinical implications in this part of the globe.
  Clinica chimica acta; international journal of clinical chemistry 05/2013;
• Article: Relationship between serum TGF-β1, OPG levels and osteoporotic risk in native Chinese women.

  Gen-Qing Xie, Dan-Dan Lei, Hong-Bo He, Jia-Ji Gong, Chao Chen, Peng Chen, Hong Zhang, Xiang-Hang Luo, Er-Yuan Liao, Xian-Ping Wu
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  ABSTRACT: BACKGROUND: Cytokines including transforming growth factor beta 1 (TGF-β1) and osteoprotegerin (OPG) are closely related to bone metabolism. However, the relationships between TGF-β1, OPG and risk of osteoporosis in native Chinese women are unknown. Our research indicated that there is a positive correlation between TGF-β1 and bone mineral density (BMD) T-score, and a negative correlation between OPG and T-score. The risk of osteoporosis is reduced as TGF-β1 increases and increases as OPG was raised. We investigated correlations of BMD T-scores with circulating TGF-β1 and BMD T-scores with circulating OPG in healthy native Chinese women, and to study the effects of changes in TGF-β1 and OPG on osteoporosis. METHODS: This was a cross-sectional study of 691 healthy native Chinese women aged 20-80 y. Concentrations of serum TGF-β1 and OPG were determined. BMD T-score at the posteroanterior spine, left hip, and forearm were measured by dual-energy X-ray absorptiometry. RESULTS: There were positive correlations between serum TGF-β1 and T-scores at the various skeletal sites (r = 0.167-0.285, all P = 0.000) and negative correlations between serum OPG and T-scores (r = -0.179 to -0.270, all P = 0.007-0.000). After adjusting for age and BMI, correlations between TGF-β1 and T-score at the lumbar vertebrae and ultradistal forearm, and between OPG and T-score at the ultradistal forearm in premenopausal subjects, remained statistically significant. Multivariate linear stepwise analysis showed that TGF-β1 could explain 1.9-8.3% of T-score variation at each skeletal site. OPG could explain 2.4-4.4% of T-score variation. When TGF-β1 and OPG concentrations were grouped according to quartile intervals, T-score and the prevalence and risk of osteoporosis varied with changes in the cytokines. CONCLUSIONS: The risk of osteoporosis in native Chinese women increased as circulating TGF-β1 was reduced and OPG was raised.
  Clinica chimica acta; international journal of clinical chemistry 05/2013;
• Article: Reevaluation of glypican-3 as a serological marker for hepatocellular carcinoma.

  Min Chen, Guohua Li, Jian Yan, Xiuzhi Lu, Jianwei Cui, Zhengxian Ni, Weizhong Cheng, Gengsun Qian, Jing Zhang, Hong Tu
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  ABSTRACT: BACKGROUND: Glypican-3 (GPC3) is a novel histochemical marker of hepatocellular carcinoma (HCC). However, its utility as a serologic marker for HCC is not conclusive. METHODS: A total of 1037 subjects, including 155 patients with HCC, 180 with chronic hepatitis, 124 with liver cirrhosis, 442 with non-HCC cancer and 136 healthy controls, were analyzed for serum GPC3 (sGPC3) by an ELISA constructed with 2 monoclonal antibodies. RESULTS: The average level of sGPC3 in HCC patients was 99.94 ± 267.2 ng/ml, which was significantly higher than in patients with chronic hepatitis (10.45 ± 46.02 ng/ml, P<0.0001), liver cirrhosis (19.44 ± 50.88 ng/ml, P=0.0013), non-HCC cancer (20.50 ± 98.33 ng/ml, P<0.0001) and healthy controls (4.14 ± 31.65 ng/ml, P<0.0001). The sensitivity of sGPC3 in HCC diagnosis was 40.0%, whereas the specificity was 98.5%, 94.4% and 87.1% in healthy controls, chronic hepatitis patients and liver cirrhosis patients, respectively. In addition, 13.5% (28/207) of lung cancer patients and 13.2% (9/68) of thyroid cancer patients had positive results with sGPC3. CONCLUSION: Serum GPC3 is a potential marker for HCC. However, the presence of sGPC3 in patients with lung cancer and thyroid cancer might limit its application as a single marker in the diagnosis of HCC.
  Clinica chimica acta; international journal of clinical chemistry 05/2013;
• Article: Relationship between adiponectin and nitrite in healthy and preeclampsia pregnancies.

  Nibia Mariana Eleuterio, Ana C T Palei, Jackeline S Rangel Machado, Jose E Tanus-Santos, Ricardo C Cavalli, Valeria C Sandrim
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  ABSTRACT: BACKGROUND: Controversial results have been reported regarding plasma adiponectin levels in preeclampsia (PE) compared to healthy pregnancies (HP). Adiponectin activates eNOS, increasing the levels of the vasodilator nitric oxide (NO). PE reduces the levels of nitrite (an NO marker) and induces higher levels of ADMA (an endogenous eNOS inhibitor) compared to HP. No previous study has examined whether a positive correlation exists between adiponectin and nitrite in HP and PE and how ADMA may interfere with this correlation. METHODS: We measured plasma nitrite concentrations using an ozone-based chemiluminescence assay, and plasma ADMA and adiponectin levels using enzyme immunoassays in 117 pregnant women (70 healthy and 47 preeclamptic). RESULTS: We found higher adiponectin levels (23.6±13.0 vs. 17.8±5.6 ng/ml; P<0.05) and lower plasma nitrite levels (104.5±84.3 vs. 177.2±151.3 nM; P<0.05) in PE compared to HP. We found a significant positive correlation between these markers in HP (r=0.3; P<0.05), but no correlation in PE. However, when we grouped PE women regarding ADMA levels (low and high levels), a strong positive correlation was found in the group with lower ADMA levels (r=0.67; P<0.05), suggesting that high ADMA concentrations may interfere with the physiological activation of eNOS by adiponectin in PE. CONCLUSIONS: Our findings showed higher levels of adiponectin and lower nitrite levels in PE compared to HP, and these levels were positively correlated in HP and in PE presenting lower concentrations of ADMA.
  Clinica chimica acta; international journal of clinical chemistry 05/2013;
• Article: Hepcidin-25: Measurement by LC-MS/MS in serum and urine, reference ranges and urinary fractional excretion.

  Fleur Wolff, Marie Deleers, Christian Melot, Béatrice Gulbis, Frédéric Cotton
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  ABSTRACT: A liquid chromatography tandem-mass spectrometry (LC-MS/MS) method was developed for reliably quantifying hepcidin-25 in human urine and serum. A 95% reference range was established for serum hepcidin-25 levels by standardizing the sampling time between 8:00 am and 11:00 am in 90 apparently healthy volunteers. The association between hepcidin-25 concentration and other biological parameters was studied using multivariable analysis and the coefficient of renal excretion of hepcidin-25 was calculated. Preanalytical variables were also investigated. The LC-MS/MS method was validated using a recent validation strategy based on accuracy profiles. Good results were obtained in terms of trueness, precision, linearity in the following dosing ranges: from 0.77 to 200 nmol/L for urine and from 0.48 to 100 nmol/L for serum. The 95% reference range of serum hepcidin-25 concentration established after excluding known conditions that affect hepcidin-25 expression was 1.5 to 15.2 nmol/L. A difference between genders was demonstrated with a median concentration of 5.5 versus 7.2 nmol/L for women and men, respectively. Serum hepcidin-25 concentrations were strongly correlated with ferritin and, to a lesser extent, with iron levels. The coefficient of renal excretion ranged from 0.1 to 16.4%. Higher values of hepcidin-25 concentrations were observed on ethylene diamine tetraacetate tubes compared to serum or lithium-heparin devices.
  Clinica chimica acta; international journal of clinical chemistry 04/2013;
• Article: Serum Adhesion Molecules, Outcome and Neuro-psychological Function in Acute Traumatic Brain Injury Patients.

  Hung-Chen Wang, Pei-Ming Wang, Yu-Jun Lin, Aij-Lie Kwan, Wei-Che Lin, Nai-Wen Tsai, Ben-Chung Cheng, Wen-Neng Chang, Ben Yu-Jih Su, Chia-Te Kung, Cheng-Hsien Lu
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  ABSTRACT: BACKGROUND: Serum concentrations of adhesion molecules may be associated with secondary brain injury after acute traumatic brain injury (TBI). METHODS: Blood samples of 68 patients admitted within 24 h after TBI were obtained on admission and on Days 4 and 7 after TBI. Patients received neuro-psychological testing on discharge and at 3 months after TBI. RESULTS: Compared to controls, patients with acute TBI had markedly increased sICAM-1 and sVCAM-1 on presentation (p=0.002 and p=0.021, respectively), but markedly decreased sL-selectin and sE-selectin (p=0.009 and p≤0.001, respectively). Outcome was assessed upon discharge using the Glasgow Outcome Scale (GOS). Good outcome was defined as GOS ≥4 and poor outcome as GOS ≤3. Motor deficits on admission (p≤0.001), Glasgow Coma Scale score on admission (p=0.002), Injury Severity Score on admission (p=0.009), neuro-surgical intervention (p=0.004), post-traumatic seizure (p=0.04), and sVCAM-1 level on admission (p=0.033) were significant risk factors of outcome. A sVCAM-1 cut-off value of 752.5 ng/ml on admission had 80.0% sensitivity and 68.1% specificity for predicting outcome. CONCLUSION: Serum adhesion molecules are not specific for predicting outcome in patients with TBI. However, higher mean levels of these molecules on admission may imply more severe inflammatory response causing secondary brain injury and worse neuro-psychological function. These molecules may be added as evaluation markers in clinical practice.
  Clinica chimica acta; international journal of clinical chemistry 04/2013;
• Article: Tissue Kallikrein is Related to the Severity of Coronary Artery Disease.

  Yu-Yu Yao, Cong Fu, Gen-Shan Ma, Yi Feng, Cheng-Xing Shen, Guo-Qiu Wu, Xiao-Guo Zhang, Jian-Dong Ding, Cheng-Chun Tang, Zhong Chen, Qi-Ming Dai, Jia-Yi Tong, Dan Luo, Jian Zhu, Hong Zhi, Yong-Jun Li, Cheng-Wei Ju, Jing Lu, Julie Chao, Lee Chao
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  ABSTRACT: BACKGROUND: The impairment of the tissue kallikrein (KLK1)-kinin system (KKS) may result in atheroma development. However, it remains unclear if the KKS correlates with coronary artery disease (CAD). METHODS: KLK1, VEGF and hs-CRP plasma levels were measured in 100 patients newly diagnosed with CAD and 33 CAD-free controls. Patients were followed-up for the incidence of major adverse cardiovascular events (MACE) for 8 months to 2 y. Gene expression of KLK1, CD105 and CD68 was assessed in human coronary endarterectomy specimens. RESULTS: Patients with CAD and acute coronary syndrome (ACS) had significantly elevated KLK1 levels. In addition, the concentration of hs-CRP was increased in ACS patients. A strong positive correlation between plasma KLK1 and the severity of CAD was also demonstrated, suggesting that high KLK1 levels are an independent predictor for CAD. MACE during follow-up significantly correlated with KLK1 levels in the ACS group. Unstable coronary plaques demonstrated markedly increased KLK1 levels, macrophage infiltration and high microvessel density. Additionally, KLK1 staining primarily colocalized with macrophages. CONCLUSIONS: In the present study, plasma KLK1 levels were a useful predictor for the presence and extent of CAD. More extensive studies are, however, necessary in order to validate these findings.
  Clinica chimica acta; international journal of clinical chemistry 04/2013;
• Article: Potential role of annexin A7 in cancers.

  Chunmei Guo, Shuqing Liu, Frederick Greenaway, Ming-Zhong Sun
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  ABSTRACT: Annexin A7 (Anxa7) is a member of the multigene annexin superfamily of Ca(2+)-regulated and phospholipid-binding proteins. Accumulated evidence indicates that the deregulation, loss of heterozygosity (LOH) and subcellular localization of Anxa7 are associated with the occurrence, invasion, metastasis and progression of a variety of cancers. Anxa7 appears to have a tumor-suppression role in glioblastoma, glioblastoma multiforme (GBM), melanoma and prostate cancer (CaP) but, controversially and interestingly, Anxa7 also appears to promote the development and malignancies of liver cancer, gastric cancer (GC), nasopharyngeal carcinoma (NPC), colorectal cancer (CRC) and breast cancer (BC). The associations between Anxa7 and malignant tumors as well as potential mechanisms of action are summarized and discussed in the current review. Anxa7 has potential for use as a biomarker for the diagnosis, treatment and prognosis of certain tumors.
  Clinica chimica acta; international journal of clinical chemistry 04/2013;
• Article: Evaluation of Four Different Equations for Calculating LDL-C with Eight Different Direct HDL-C Assays.

  Marcelo Jose Andrade Oliveira, Hendrick E van Deventer, Lorin M Bachmann, G Russell Warnick, Katsuyuki Nakajima, Masakasu Nakamura, Ikunosuke Sakurabayashi, Mary M Kimberly, Robert D Shamburek, William J Korzun, Gary L Myers, W Greg Miller, Alan T Remaley
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  ABSTRACT: BACKGROUND: Low-density lipoprotein-cholesterol (LDL-C) is often calculated (cLDL-C) by the Friedewald equation, which requires high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG). Because there have been considerable changes in the measurement of HDL-C with the introduction of direct assays, several alternative equations have recently been proposed. METHODS: We compared 4 equations (Friedewald, Vujovic, Chen, and Anandaraja) for cLDL-C, using 8 different direct HDL-C (dHDL-C) methods. LDL-C values were calculated by the 4 equations and determined by the β quantification reference method procedure in 164 subjects. RESULTS: For normotriglyceridemic samples (TG<200mg/dl), between 6.2 to 24.8% of all results exceeded the total error goal of 12% for LDL-C, depending on the dHDL-C assay and cLDL-C equation used. Friedewald equation was found to be the optimum equation for most but not all dHDL-C assays, typically leading to less than 10% misclassification of cardiovascular risk based on LDL-C. Hypertriglyceridemic samples (>200mg/dl) showed a large cardiovascular risk misclassification rate (30 - 50%) for all combinations of dHDL-C assays and cLDL-C equations. CONCLUSION: Friedewald equation showed the best performance for estimating LDL-C, but its accuracy varied considerably depending on the specific dHDL-C assay used. None of the cLDL-C equations performed adequately for hypertriglyceridemic samples.
  Clinica chimica acta; international journal of clinical chemistry 04/2013;
• Article: Development and validation of a sensitive and robust LC-MS/MS with electrospray ionization method for simultaneous quantitation of quetiapine and its active metabolite norquetiapine in human plasma.

  Xin Xiong, Li Yang, Jingli Duan
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  ABSTRACT: BACKGROUND: Quetiapine is an atypical antipsychotic agent for the treatment of schizophrenia, acute mania, and acute bipolar depression. The antidepressive response is considered to be mediated by the metabolite norquetiapine (N-desalkylquetiapine), and the aim of this study was to develop a LC-MS/MS method to measure concentrations of these compounds in human plasma. METHODS: Following one step liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a Sunfire C18 column (50 mm×2.1 mm, 5 μm). The retention times were 2.12, 2.24, 2.12 and 2.19 min for quetiapine, norquetiapine and their respective stable labeled internal standards, respectively. Cycle time was 4 min. Selected reaction monitoring (SRM) in positive ion mode was used for quantitation. RESULTS: The present method exhibited a linear dynamic range of 0.5-500 ng/ml for quetiapine and 0.6-600 ng/ml for norquetiapine. The applicable range was extended by dilution up to 5-fold with blank matrix. The accuracy and precision for quetiapine were <103.0% and 8.8%, for norquetiapine were <108.8% and 11.1%, respectively. CONCLUSIONS: A rapid, sensitive, and robust LC-MS/MS method for quantifying quetiapine and its metabolite norquetiapine levels in human plasma was validated and successfully applied to samples from schizophrenic patients in clinical pharmacokinetics studies.
  Clinica chimica acta; international journal of clinical chemistry 04/2013;
• Article: Circulating tumor cells in breast cancer.

  Malgorzata Banys, Volkmar Müller, Carola Melcher, Bahriye Aktas, Sabine Kasimir-Bauer, Carsten Hagenbeck, Andreas Hartkopf, Tanja Fehm
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  ABSTRACT: Detection of disseminated tumor cells (DTCs) in bone marrow and of circulating tumor cells (CTCs) in the blood has become a major focus of translational cancer research. DTC presence is a common phenomenon seen in 30-40% of primary breast cancer patients and is strongly associated with poor clinical outcome. Since bone marrow biopsy is an invasive procedure, evaluation of CTCs might become a desired alternative. Recent clinical trials have shown CTC detection to be a promising prognostic tool in both primary and metastatic setting. Evaluation of CTCs might be useful for therapy monitoring and their characterization might help to identify novel targets for biological therapies aimed at disrupting earliest steps of metastatic cascade.
  Clinica chimica acta; international journal of clinical chemistry 04/2013;
• Article: Proteomics reveals plasma profiles for monitoring the toxicity caused by chromium compounds.

  Jia-You Fang, Tung-Ho Wu, Chun-Hsun Huang, Pei-Wen Wang, Chih-Chieh Chen, Yang-Chang Wu, Tai-Long Pan
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  ABSTRACT: BACKGROUND: Today, various heavy metals are widespread in the ecosystem and have become important environmental contaminants. Exposure to these hazardous metals such as chromium usually results in cytotoxicity and large-scale protein changes which reflect pathologic states. METHODS: We used a comprehensive proteomic tool to survey changes in plasma proteins elicited by two chromium species (Cr(6+) and Cr(3+)). RT-PCR was applied to evaluate levels of cytokines associated with adverse responses. Lectin blotting was used to investigate the contents of fucosylated proteins. RESULTS: Protein profiles revealed statistically significant changes in the intensity of 12 proteins. The network analysis implied that Cr(6+) application strongly induced the IL-6-stimulated inflammatory pathway. mRNA levels of specific cytokines were also correlated with inflammatory events. Increased IL-6 modulation of the fucosylation of haptoglobin was also identified in Cr(6+)-treated samples. CONCLUSIONS: These results suggest that Cr(6+) may induce IL-6-mediated inflammatory responses which result in hepatic injury. This paper highlights the applications of functional proteomics of plasma profiles and fucosylated glycoproteins as a predictive tool to monitor human health in contact with chromium.
  Clinica chimica acta; international journal of clinical chemistry 04/2013;
• Article: Simultaneous UPLC- MS/MS assay for the detection of the traditional antipsychotics haloperidol, fluphenazine, perphenazine, and thiothixene in serum and plasma.

  Joetta M Juenke, Paul I Brown, Francis M Urry, Kamisha L Johnson-Davis, Gwendolyn A McMillin
  Clinica chimica acta; international journal of clinical chemistry 04/2013;