Epigenomes

Clinical Chemistry and Laboratory Medicine 46 (5): 731-731

Clinical Chemistry and Laboratory Medicine 46 (5): 729-730

Clinical Chemistry and Laboratory Medicine 46 (5): 727-728

Clinical Chemistry and Laboratory Medicine 46 (5): 725-726

Clinical Chemistry and Laboratory Medicine 46 (5): 722-724

Clinical Chemistry and Laboratory Medicine 46 (5): 717-721

Clinical Chemistry and Laboratory Medicine 46 (5): 714-716 Abstract Background: Due to the increasing migration flows mostly concerning Western countries, the problem of reference ranges and cut-off values is a living matter. In particular, the influence of ethnic origin on traditional and novel biochemical markers of cardiac damage, including cardiac troponin T (cTnT), ischemia modified albumin (IMA) and N-terminal prohormone brain natriuretic peptide (NT-proBNP), has not been investigated, to the best of our knowledge. Methods: CTnT, NT-proBNP and IMA were assayed by a Modular System in 34 apparently healthy black Africans originating mainly from Central Africa and in 34 apparently healthy white, non-immigrant Italians, matched for age and sex. Results: All the subjects investigated displayed cTnT values <0.01 ng/mL. Black Africans displayed significantly increased concentrations of serum IMA (107 vs. 92 kU/L, p<0.0001), but not of NT-proBNP (4.9 vs. 3.8 pmol/L, p=0.4), as compared to the white, non-immigrant Italians. Conclusions: The results of our investigation indicate that the reference ranges and the thresholds values of IMA, but not those of cTnT and NT-proBNP, may be different according to the ethnic origin of the population. Therefore, although the current decisional thresholds of both cTnT and NT-proBNP may be appropriate for diagnosing cardiac damage and dysfunction in the black African population, that of IMA may require a revision toward higher values. Clin Chem Lab Med 2008;46:714–6.

Clinical Chemistry and Laboratory Medicine 46 (5): 703-713 Abstract Background: Preservation of urine samples is important for centralised laboratory services with automated instruments. Methods: A multicentre evaluation was carried out to assess preservative tubes from BD Diagnostics-Pre-analytical Systems and from Greiner Bio-One for test strip reading (documented at the level of remission values), for particle counting by flow cytometers (UF-100) and for visual microscopy. Failures were expressed as percentages of originally positive samples beyond a two-fold change (+100% or –50%) from the original values. Results: The preservative-containing BD Plus C&S plastic, BD Plus UAP and Greiner Stabilur tubes succeeded in preservation of test strip results for 6–24 h (exceptions were glucose and nitrite tests). Greiner boric acid tube showed false negative results in leukocyte, protein and ketone strip tests immediately after adding the preservative. Urine red blood cell counts (with Sysmex UF-100) were preserved for 5 h in BD Plus C&S plastic and Greiner Stabilur tubes (Greiner tubes having clearly larger preservative-related background). Bacteria or white blood cell counting succeeded in BD Plus C&S plastic tubes for 5 or 24 h, respectively, but up to 72 h in Greiner Stabilur tubes. In visual microscopy, the Greiner Stabilur tube was slightly better than the BD Plus C&S plastic tube. Conclusions: Urine specimens can be transported at +20°C on the day of collection if preserved properly. Longer delays need careful planning with current preservatives. Flow cytometry with UF-100 is sensitive to non-dissolved preservative remnants. Clin Chem Lab Med 2008;46:703–13.

Clinical Chemistry and Laboratory Medicine 46 (5): 699-702 Abstract Background: Serum γ-glutamyltransferase (GGT) and erythrocyte mean corpuscular volume (MCV) are well-known biological markers of excessive ethanol consumption. Methods: The beverage-specific effects of ethanol consumption on GGT level and MCV value were analyzed cross-sectionally and retrospectively among middle-aged Japanese men who underwent a retirement health checkup (n=974). Results: Both the consumption of distilled alcohol and that of fermented alcohol positively correlated with the logarithm of GGT [standard regression coefficient (β) 0.261 and 0.174, respectively]. The prevalence rate of elevated GGT levels (≥70 IU/L) was higher among heavy drinkers of distilled alcohol than among heavy drinkers of fermented alcohol (38.8% vs. 27.6%, p=0.013). The MCV value correlated with distilled alcohol consumption (β: 0.212, p<0.0001) but not with fermented alcohol consumption (β: 0.043, not significant). The prevalence rate of an elevated MCV (≥97 fL) was higher among heavy drinkers of distilled alcohol than among heavy drinkers of fermented alcohol (35.3% vs. 16.8%, p<0.001). Conclusions: These results suggest that MCV is less sensitive for detecting heavy consumption of fermented alcohol than for detecting that of distilled alcohol in apparently healthy middle-aged men. Clin Chem Lab Med 2008;46:699–702.

Clinical Chemistry and Laboratory Medicine 46 (5): 691-698 Abstract Background: A reference interval (RI) is usually derived from a data set obtained cross-sectionally without consideration of the long-term analytical coefficient of variation (CV) (CVA) or within-individual CV (CVI). Methods: A total of 135 healthy volunteers, 22–59 years of age, working in eight clinical laboratories in Japan participated in a study to determine RIs for 26 commonly measured biochemical analytes. Blood samples were collected monthly for 1 year and measured in each laboratory. Common quality control (QC) specimens were measured monthly. RIs were derived parametrically using a modified Box-Cox power transformation method. Subjects with abnormal results for test items other than the one for derivation were excluded. Results: Although there was no statistically significant between-month variation, unacceptably large between-laboratory differences were observed in QC test results. Thus, all values were transformed to those of the main laboratory based on cross-check test results. CVI values computed by two-level nested analysis of variance were generally greater than those commonly cited in the literature. Average RIs derived from the monthly results agreed well with those derived from the entire results. However, CVs of lower and upper limits of the monthly RIs were greater than CVA. Conclusions: To derive reliable RIs, it is important to consider long-term variability of CVI and CVA. Clin Chem Lab Med 2008;46:691–8.

Clinical Chemistry and Laboratory Medicine 46 (5): 687-690 Abstract Background: The usefulness of serum antibodies to common food antigens (immunoglobulin G4; IgG4) assay in management of patients suffering from food intolerance was assessed. Methods: A total of 22 asymptomatic healthy subjects and 68 patients with symptoms referred for suspected food intolerance were studied. Serum IgG4 to 19 common foods was measured by an automated immunoassay. Results: The area under the receiver operating characteristic curve was 0.92 (standard error 0.04) and, at a threshold value of 2.3 U/mL, the IgG4 determination had a sensitivity of 0.81, with a specificity of 0.87. With a pre-test probability of 5% and 20%, the post-test probability of having disease was found to be 24% and 61%, respectively, and 1.1% and 5% if the result was negative. Cohen’s κ value (0.83) indicated a good agreement between symptoms and IgG4 concentrations. Conclusion: Serum IgG4 assay may play a role in ruling out food intolerance, because of its satisfactory negative predictive value (0.99). Clin Chem Lab Med 2008;46:687–90.

Clinical Chemistry and Laboratory Medicine 46 (5): 680-686 Abstract Background: Carnitine blood levels are closely related to β-oxidation and implicated with strenuous muscle contractions. Normal delivery process is characterized by the participation of the uterus and most skeletal muscles. Methods: Women with normal pregnancy (n=56) were divided into two groups. Group A (n=26) with normal labor and vaginal delivery and group B (n=30) with scheduled cesarean section. Blood was obtained from the mothers at the beginning of labor and immediately after delivery (pre- vs. post-delivery), as well as from the cord blood (CB). Total antioxidant status (TAS) was measured with a commercial kit and carnitine was measured in blood spots on Guthrie cards with tandem-mass spectrometry. Results: TAS and carnitine levels were similar in all the groups pre-delivery. In contrast, TAS and carnitine levels were significantly lower in group A than in group B post-delivery. Remarkably lower TAS and carnitine levels were measured in the CB of neonates of group A as compared to the CB of neonates of group B. Conclusions: The lower TAS and carnitine levels measured in group A as compared to group B post-delivery may be due to uterus and skeletal muscle contraction during a normal labor process. Infants born with scheduled cesarean section are benefited with high carnitine levels to face oxidation perinatally. Clin Chem Lab Med 2008;46:680–6.

Clinical Chemistry and Laboratory Medicine 46 (5): 674-679 Abstract Background: Hypothyroidism is the second most prevalent disorder in India and most cases require lifelong treatment. Disordered myocardial function is one of the complications of overt hypothyroidism. Dyslipidemia and lipid peroxidation are two biochemical derangements of hypothyroidism and both have been found to be associated. Still uncertainty remains regarding the origin of lipid peroxidation in this clinical condition. Besides, thyroid stimulating hormone or thyrotropin at a higher concentration can induce secretion of inflammatory cytokines and decrease the antioxidant status. Methods: Hence, we analyzed the association of lipid risk factors and thyrotropin in hypothyroidism with the extent of lipid peroxidation. A total of 42 primary hypothyroid patients volunteered to give fasting blood samples prior to therapy for the analysis of oxidative stress, thyroid and lipid profiles. Results: Oxidative stress was confirmed by the increased levels of malondialdehyde and protein carbonylation and decreased levels of reduced glutathione. Simple correlation analyses revealed the association of lipid peroxidation with both thyrotropin and lipid risk factors. Partial correlation analyses showed that thyrotropin and lipid risk factors mutually influence their association with the higher malondialdehyde levels in these patients. Conclusions: Hyperthyrotropinemia may be considered not only as an index of the severity of hypothyroidism but also of the extent of the associated lipid peroxidation. Clin Chem Lab Med 2008;46:674–9.

Clinical Chemistry and Laboratory Medicine 46 (5): 667-673 Abstract Background: Synergistic interactions between elevated serum lipoprotein(a) [Lp(a)] and other unfavorable risk factors have been proposed to cause very high risk for coronary artery disease (CAD). The aim of this study was to examine the potential interactions between Lp(a) and other risk factors. Methods: The profiles of serum (apo)(lipo)proteins, markers of inflammation, indicators of hemoconcentration as well as classical risk factors were determined in 264 clinically stable angiographically documented subjects. Correlation, linear and logistic regression and stratification analyses were performed. Results: The frequency and severity of CAD and the prevalence of diabetes mellitus were significantly higher in the 3rd relative to 1st tertile of Lp(a). Subjects with Lp(a) levels in the upper tertile had significantly higher levels of serum glucose, total cholesterol and low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), calcium, phosphate and their ion product. Bivariate correlation analysis indicated that serum Lp(a) was associated positively with the occurrence and severity of CAD, diabetes mellitus and the levels of serum glucose, cholesterol, LDL-C, apoB, calcium, phosphate and inversely to physical inactivity. In linear regression analysis, LDL-C (or apoB), diabetes, physical inactivity and phosphate were the major independent determinants of Lp(a) values. In multiple logistic regression analysis, after adjusting for major risk factors, Lp(a) showed a significant and independent association with the prevalence of CAD. By constructing dummy combined variables, elevated Lp(a) accompanied with diabetes or high levels of serum glucose, apoB and cholesterol exhibited an amplified high risk for CAD. Conclusions: The results indicate that serum Lp(a) does interact multiplicatively with diabetes, apoB and cholesterol. The simultaneous assessment of Lp(a) and interactive risk factors enhances the discriminating value for CAD. Clin Chem Lab Med 2008;46:667–73.

Clinical Chemistry and Laboratory Medicine 46 (5): 660-666 Abstract Background: Elevated procalcitonin (PCT) levels are observed after major surgery, such as orthotopic liver transplantation (OLTx). The aim of this observational study was to evaluate PCT kinetics during the first 5 following days after surgery to establish the prognostic value of PCT changes in the outcome of OLTx, and to predict medical, technical and infectious complications. PCT was also evaluated in the differential diagnosis of infection vs. rejection. Methods: A total of 64 OLTx were performed in 58 patients; they were split into two groups: with and without complications. Out of these patients, 18 developed infection, and nine rejection. PCT was measured before and during surgery, 12 h after transplantation and daily for the 5 following days. PCT was also measured the day when infection or rejection was diagnosed, and on the previous day. PCT was determined by time-resolved amplified cryptate emission (TRACE) technology. Results: PCT elevation began at 12 h after surgery, reaching a peak on the 1st day in both groups. Significantly higher PCT concentrations were found in the group of patients developing complications, on the 5 postoperative days. It was found that a 24 h PCT value higher than 1.92 μg/L increased by 9.1-time-fold the risk of complications. When infection was diagnosed, a second peak of PCT was observed, but no PCT elevation was shown in rejection. Conclusions: Daily monitored PCT provides valuable information about the early outcome of OLTx. Clin Chem Lab Med 2008;46:660–6.

Clinical Chemistry and Laboratory Medicine 46 (5): 655-659 Abstract Background: Hyperhomocysteinemia has been associated with an increased risk of venous thrombosis, which might be mediated through an oxidative stress dependent mechanism. The function of uncoupling protein-2 (UCP2) is still under debate, but it has been suggested to play a role in reduction of mitochondrial reactive oxygen species. In the present study, we investigated whether the 45 bp deletion/insertion (del/ins) polymorphism in the UCP2 gene is associated with elevated homocysteine levels and whether it might be associated with an increased risk of recurrent venous thrombosis (RVT). Methods: The 45 bp del/ins polymorphism in the UCP2 gene was genotyped by PCR analysis in 161 RVT cases and 386 controls of Caucasian origin in which fasting- and post-load homocysteine levels were previously determined. Statistical analysis was performed to assess whether the UCP2 45 bp del/ins polymorphism was associated with plasma total homocysteine levels and venous thrombosis risk. Results: Post-load homocysteine levels were positively associated with UCP2 45 bp ins/ins genotype (p=0.02). None of the UCP2 45 bp ins/del genotypes were associated with fasting plasma homocysteine levels. The frequency of the UCP2 45 bp ins/ins genotype was 12.4% in RVT cases compared to 8.3% in controls, which resulted in an odds ratio of 1.8 (95% CI 1.0–3.4). Conclusions: The results of our study show that the common 45 bp del/ins polymorphism in the UCP2 gene is associated with hyperhomocysteinemia, which might increase the risk of venous thrombosis. However, the mechanism is not fully understood and additional studies should be performed to confirm our findings. Clin Chem Lab Med 2008;46:655–9.

Clinical Chemistry and Laboratory Medicine 46 (5): 648-654 Abstract Background: Studies have associated elevated plasma levels of the thiols homocysteine and cysteine with an increased risk of atherosclerosis. Their relationship with systemic inflammatory parameters and sclerosis scores was investigated in this study. Methods: Total homocysteine, total cysteine, neopterin and C-reactive protein (CRP) concentrations were measured in blood samples of 242 patients undergoing elective coronary angiography. A total of 181 patients had coronary artery disease (CAD), as defined by occlusion of >75% of at least one of the three main coronary arteries, and 61 subjects did not have relevant coronary stenoses. Results: Total cysteine concentrations were higher in patients suffering from coronary artery sclerosis with stepwise increases relative to the extent of coronary artery sclerosis (p<0.001). In contrast, neither total homocysteine nor the inflammatory markers, CRP and neopterin, differed between patients and controls. However, total homocysteine concentrations correlated with total cysteine (r=0.468) and neopterin concentrations (r=0.290), as well as serum creatinine (r=0.226; all p<0.001), the latter indicating a dependence of total homocysteine concentrations on kidney function. Total cysteine concentrations were associated with increased neopterin levels (r=0.231, p<0.001). Conclusions: Total cysteine concentrations were well suited to estimate the extent of coronary artery sclerosis, while in our study of stable CAD patients total homocysteine was not increased compared to controls. The association between homocysteine, cysteine and parameters of immune activation and inflammation in our study suggests that these markers of CAD may be interdependent. Clin Chem Lab Med 2008;46:648–54.

Clinical Chemistry and Laboratory Medicine 46 (5): 639-647 Abstract Background: The choice of parameter sets used to calculate Down’s syndrome risks is important. This study details analysis of samples from affected and unaffected pregnancies and evaluates whether published population data is optimal. Screening efficiency realized with measurement procedure-specific population parameters is compared with selected population sets available in the literature. Methods: In a retrospective experiment, double and triple testing was performed on maternal serum samples from 286 randomly chosen unaffected singleton pregnancies and 95 Down’s syndrome affected pregnancy samples. Using a risk cut-off of 1 in 250, detection rates and false positive rates were estimated for different population settings to select a model giving the best overall efficacy. Receiver operation characteristics curve analysis was performed and detection rates realized with the different population settings was estimated at a 5% fixed false positive rate. Results: Geometric mean weight corrected multiples of the median values were 1.01 for α-fetoprotein (AFP), 1.02 for human chorionic gonadotropin (hCG) and 1.01 for unconjugated estriol (uE3) in unaffected pregnancies and 0.77 (95% CI: 0.71–0.83) for AFP, 2.42 (95% CI: 2.17–2.71) for hCG and 0.78 (95% CI: 0.73–0.83) for uE3 in affected pregnancies. Differences in double and triple risks obtained with the different models were significantly different from each other (p<0.001). At a cut-off of 1 in 250, the maximum triple test detection rate was 75.8% for a false positive rate of 4.9% and was obtained with the measurement procedure-specific setting. At a fixed false positive rate of 5%, the maximum detection rate for the triple test was 77.9% (95% CI: 62.2%–85.8%). The maximum double test detection rate at 5% false positive rate was 69.6% (95% CI: 59.5%–78.5%). Except for two models, the area under the curve for the triple test was higher than that of the double test. Conclusions: The Access triple test meets the typical performance characteristics for this test combination. The assay-specific settings yielded the overall best efficacy for the criteria studied. Therefore, the availability of measurement procedure-specific mid-trimester reference values for unaffected and affected pregnancies in prenatal screening programs is essential. Such reference values are established for the Beckman Coulter Access triple test: maternal serum AFP, uE3 and hCG. Clin Chem Lab Med 2008;46:639–47.

Clinical Chemistry and Laboratory Medicine 46 (5): 630-638 Abstract Background: The point-of-care (POC) test Roche CARDIAC CK-MB is a new assay which has been developed for the existing Roche Cardiac reader system. Methods: We performed a multicentre evaluation at six sites to assess the analytical performance of the POC CK-MB assay and to compare it with a quantitative laboratory CK-MB assay. Results: Within-series coefficients of variation (CV) resulting from 34 ten-fold measurements with patient samples ranged from 4.3% to 16.4%. Using quality control material, the mean CV values for day-to-day imprecision were 6.5% for the low level control and 8.4% for the high level control. Based upon 847 pairs of values, the mean relative bias of three independently calibrated lots of the POC CK-MB assay ranged from –6% to –11% in method comparisons with the lab CK-MB assay. The mean relative lot-to-lot differences of POC CK-MB were between –2% and +1%. No interference was observed with lipaemic blood (triglyceride concentrations up to 8.1 mmol/L), icteric blood (bilirubin concentrations up to 513 μmol/L), haemolytic blood (haemoglobin concentrations up to 0.12 mmol/L), biotin (up to 30 mg/L) and rheumatoid factor (up to 119 IU/mL), or with 53 standard or cardiological drugs even in toxic concentrations. There was no influence on the results by varying haematocrit values in the range from 21% to 54%. A slight interference with human anti-mouse antibodies type 2 was found. No significant influence on the results with POC CK-MB was found by using sample volumes between 135 and 165 μL. High CK-MB concentrations above the measuring range of POC CK-MB (1–40 μg/L) did not lead to false low results due to potential high-dose hook effect. No significant effect of sample age on recovery occurred up to a sample age of 24 h. No cross-reactivity was found between the POC CK-MB assay and either CK-MM or CK-BB. A substudy with healthy individuals confirmed the reference limits of 3.8 μg/L for females and 6.7 μg/L for males. Conclusions: The POC CK-MB assay showed a very good analytical performance with an excellent concordance with the calibration and reference laboratory method. It should be therefore suitable for its intended use in POC settings. Clin Chem Lab Med 2008;46:630–8.

Clinical Chemistry and Laboratory Medicine 46 (5): 623-629 Abstract Background: The metrological traceability of prostate-specific antigen (PSA) assay calibration to WHO standards is desirable to potentially improve the comparability between PSA assays. A method comparison was performed between the traditionally standardized Beckman Coulter Hybritech Access PSA and free PSA (fPSA) assays and a new alternate calibration of assays aligned to the WHO standards 96/670 and 96/668, respectively. Methods: Sera from 641 men with and without prostate cancer, various control materials and mixtures of different proportions of the WHO standards were measured with both assay calibrations. Results: Excellent comparability between the corresponding assay calibrations was observed, with correlation coefficients of at least 0.996. The Passing-Bablok slopes were 0.747 for total PSA (tPSA), 0.776 for fPSA and 1.02 for the percentage ratio of fPSA to tPSA (%fPSA), while the corresponding percentages of the new WHO-aligned assay results related to the traditional assays were 76.2%, 77% and 102.2%. Receiver operating characteristics revealed no differences between the two PSA assay calibrations. Conclusions: The WHO calibration yields results approximately 25% lower for tPSA and fPSA values when compared with the conventional Hybritech calibration. Using the WHO-aligned PSA assay, a tPSA cut-off of 3 μg/L should be considered in clinical practice, while %fPSA cut-offs could be retained. Clin Chem Lab Med 2008;46:623–9.

Clinical Chemistry and Laboratory Medicine 46 (5): 612-622 Abstract Background: Cancer antigen CA15-3 antigen is known as a valuable marker for the management of breast cancer. Methods: The analytical and clinical performance of the Access® BR Monitor Immunoassay System (Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA15-3 on the Elecsys® System (Roche Diagnostics). Results: Total imprecision (%CV) of the BR Monitor ranged between 5.5% and 11.7%, and inter-laboratory reproducibility between 3.4% and 5.1%. Linearity upon dilution showed a mean recovery of 98.5% (SD±9.1%). Endogenous interferents had no influence on BR Monitor levels (mean recoveries: hemoglobin 112%, bilirubin 111%, triglycerides 108%). There was no high-dose hook effect up to 13,540 kU/L. Clinical performance investigated in sera from 1811 individuals showed a general correlation between the Access BR Monitor and Elecsys CA15-3 (R=0.797), with a slope of 1.383. CA15-3 serum levels, as measured by the BR Monitor, were low in healthy individuals (n=267, median=11.9 kU/L, 95th percentile=23.5 kU/L), higher in individuals with various benign diseases (n=549, medians=11.3–15.6 kU/L, 95th percentiles=21.6–54.6 kU/L) and even higher in individuals suffering from various cancers (n=995, medians=11.2–22.8 kU/L, 95th percentiles=30.0–429.7 kU/L). Best diagnostic accuracy for cancer detection against the relevant benign control group by the BR Monitor was found for locoregional and metastatic breast cancer, as well as for ovarian cancer [area under the curve (AUC) 0.619, 0.897 and 0.774]. Results for the reference CA15-3 assay were comparable (AUC 0.611, 0.887 and 0.818). Conclusions: The Access BR Monitor provides accurate methodological characteristics and demonstrates an analytical and clinical correlation with Elecsys CA15-3. Best diagnostic accuracy for the BR Monitor was found in breast and ovarian cancer. Our results also suggest a clinical value of the BR Monitor in other cancers. Clin Chem Lab Med 2008;46:612–22.

Clinical Chemistry and Laboratory Medicine 46 (5): 600-611 Abstract Background: Gastrointestinal cancer antigen CA19-9 is known as a valuable marker for the management of patients with pancreatic cancer. Methods: The analytical and clinical performance of the Access® GI Monitor assay (Beckman Coulter) was evaluated on the UniCel® DxI 800 Immunoassay System at five different European sites and compared with a reference method, defined as CA19-9 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the GI Monitor ranged between 3.4% and 7.7%, and inter-laboratory reproducibility between 3.6% and 4.0%. Linearity upon dilution showed a mean recovery of 97.4% (SD+7.2%). Endogenous interferents had no influence on GI Monitor levels (mean recoveries: hemoglobin 103%, bilirubin 106%, triglycerides 106%). There was no high-dose hook effect up to 115,000 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access® GI Monitor and Elecsys CA19-9 (R=0.959, slope=1.004, intercept=+0.17). GI Monitor serum levels were low in healthy individuals (n=267, median=6.0 kU/L, 95th percentile=23.1 kU/L), higher in individuals with various benign diseases (n=550, medians=5.8–13.4 kU/L, 95th percentiles=30.1–195.5kU/L) and even higher in individuals suffering from various cancers (n=995, medians=8.4–233.8 kU/L, 95th percentiles=53.7–13,902 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the GI Monitor was found for pancreatic cancer [area under the curve (AUC) 0.83]. Results for the reference CA19-9 assay were comparable (AUC 0.85). Conclusions: The Access® GI Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with the Elecsys CA19-9. The GI Monitor shows the best diagnostic accuracy in pancreatic cancer. Our results also suggest a clinical value of the GI Monitor in other cancers. Clin Chem Lab Med 2008;46:600–11.

Clinical Chemistry and Laboratory Medicine 46 (5): 588-599 Abstract Background: Cancer antigen CA125 is known as a valuable marker for the management of ovarian cancer. Methods: The analytical and clinical performance of the Access OV Monitor Immunoassay System (Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA125 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the OV Monitor ranged between 3.1% and 8.8%, and inter-laboratory reproducibility between 4.7% and 5.0%. Linearity upon dilution showed a mean recovery of 100% (SD+8.1%). Endogenous interferents had no influence on OV Monitor levels (mean recoveries: hemoglobin 107%, bilirubin 103%, triglycerides 103%). There was no high-dose hook effect up to 27,193 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access OV Monitor and Elecsys CA125 (R=0.982, slope=0.921, intercept=+1.951). OV Monitor serum levels were low in healthy individuals (n=267, median=9.7 kU/L, 95th percentile=30.8 kU/L), higher in individuals with various benign diseases (n=549, medians=10.9–16.4 kU/L, 95th percentiles=44.2–355 kU/L) and even higher in individuals suffering from various cancers (n=995, medians=12.4–445 kU/L; 95th percentiles=53.4–4664 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the OV Monitor was found for ovarian cancer [area under the curve (AUC) 0.898]. Results for the reference CA125 assay were comparable (AUC 0.899). Conclusions: The Access OV Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with Elecsys CA125. The best diagnostic accuracy for the OV Monitor was found in ovarian cancer. Our results also suggest a clinical value of the OV Monitor in other cancers. Clin Chem Lab Med 2008;46:588–99.

Clinical Chemistry and Laboratory Medicine 46 (5): 577-587 Abstract Due to their pathogenetic role, many serum auto-antibodies can be detected a long time before the clinical onset and during the course of organ-specific autoimmune diseases. For these reasons, autoantibodies can be used as predictive markers of an ongoing disease (in healthy subjects) and of disease activity and severity (in ill patients). The new multiplex diagnostic technologies introduced recently in laboratory medicine allow the simultaneous detection of several different autoantibodies and can be used for screening purposes in open populations or high-risk groups. This review examines the various autoantibodies of demonstrated predictive role in organ-specific autoimmune diseases and it introduces the state-of-the-art in the detection of multiple autoantibodies with proteomic systems. Clin Chem Lab Med 2008;46:577–87.