BACKGROUND Integrated systems that combine clinical chemistry and immunoassay analyzers are used routinely. Sample to sample carryover is an inherent risk and can cause erroneously high patient test results for immunoassays. IVD manufacturers and laboratories must be aware of this phenomenon and guard against it. METHODS We used a sample carryover protocol that directs the clinical chemistry module to process samples with very high immunoassay analyte concentrations followed by samples with very low concentrations for the same analyte. Low concentration samples were then tested by the immunoassay module to determine if the clinical chemistry module caused primary sample tube to primary sample tube carryover of the immunoassay analyte. RESULTS Sample carryover was assessed on the Abbott ci8200 for HBsAg, AFP, beta-hCG, and PSA. Observed HBsAg carryover met the design specification of <0.1 ppm. Carryover for the other analytes was <0.1 ppm or below the assay limit of detection. CONCLUSIONS IVD manufacturers must design integrated systems to minimize primary specimen tube carryover and avoid analytical laboratory error that can impact patient safety. Carryover testing is difficult for clinical laboratories to perform in order to verify system performance. Laboratories must consider the potential for specimen carryover and its impact on results whether moving primary sample tubes between separate analyzers or using an integrated system.

Development and progression of colon cancer may be related to cytokines. Cytokines with diagnostic value have been identified individually but have not been implemented into clinical praxis. Using a multiplex protein array, the authors explore a panel of cytokines simultaneously and compared its performance to carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). Serum concentrations of 12 cytokines were simultaneously determined by multiplex biochip technology in 50 colon cancer patients and 50 healthy controls. Serum levels of interleukin-8 (IL-8) and CEA were significantly higher in cancer patients than in healthy controls. Areas under the receiver operating characteristic curves (AUCs) were largest for IL-8, followed by CEA, vascular endothelial growth factor (VEGF), and CA 19-9. Analyses regarding marker combinations showed an advantage over single marker performance for CEA, VEGF, and CA 19-9 but not for IL-8. Multiplex biochip array technology represents a practical tool in cytokine and cancer research when simultaneous determination of different biomarkers is of interest. The results suggest that the assessment of IL-8, CEA, VEGF, and possibly CA 19-9 serum levels could be useful for colon cancer screening with the potential of also detecting early stage tumors. Further validation studies using these and additional markers on a multiplex array format are encouraged.

Major depressive disorder (MDD) is associated with increased volumes of visceral fat and a high prevalence of the metabolic syndrome. In turn, affective disorders are frequently found in patients with borderline personality disorder (BPD). It is therefore unclear whether BPD per se may influence body composition. In order to clarify a potential relationship between BPD and body composition, we measured visceral fat content (VFC) in young depressed women with and without comorbid BPD and related this parameter to various features of the metabolic syndrome. Visceral fat content was measured by magnetic resonance imaging in 22 premenopausal women with MDD only, in 44 women with comorbid MDD and BPD, in 12 female BPD patients without MDD, and in 34 healthy women (CG). Data showed that depressed women without comorbid BPD had a 335% higher VFC and women with comorbid BPD had a 250% higher VFC than the CG women. When controlling for age, data showed significant effects of MDD on VFC (F = 8.4; P = 0.005). However, BPD, with or without MDD, was not related to VFC. Young depressed women with and without comorbid BPD display increased visceral fat content when compared to control subjects and may therefore constitute a risk group for the development of the metabolic syndrome. BPD per se is not an additive risk factor in this context.

BACKGROUND The current study was designed to determine the relation between preoperative cerebral oxygen saturation (Sco2), variables of cardiopulmonary function, mortality, and morbidity in a heterogeneous cohort of cardiac surgery patients. METHODS In this study, 1,178 consecutive patients scheduled for on-pump surgery were prospectively studied. Preoperative Sco2, demographics, N-terminal pro-B-type natriuretic peptide, high-sensitive troponin T, clinical outcomes, and 30-day and 1-yr mortality were recorded. RESULTS Median additive EuroSCORE was 5 (range: 0-19). Thirty-day and 1-yr mortality and major morbidity (at least two major complications and/or a high-dependency unit stay of at least 10 days) were 3.5%, 7.7%, and 13.3%, respectively. Median minimal preoperative oxygen supplemented Sco2 (Sco2min-ox) was 64%(range: 15-92%). Sco2min-ox was correlated (all: P value <0.0001) with N-terminal pro-B-type natriuretic peptide (ρ:-0.35), high-sensitive troponin T (ρ:-0.28), hematocrit (ρ: 0.34), glomerular filtration rate (ρ: 0.19), EuroSCORE (τ: 0.20), and left ventricular ejection fraction class (τ: 0.12). Thirty-day nonsurvivors had a lower Sco2min-ox than survivors (median 58%[95% CI, 50.7-62%] vs. 64%[95% CI, 64-65%]; P < 0.0001). Receiver-operating curve analysis of Sco2min-ox and 30-day mortality revealed an area-under-the-curve of 0.71 (95% CI, 0.68-0.73%; P < 0.0001) in the total cohort and an area-under-the-curve of 0.77 (95% CI, 0.69-0.86%; P < 0.0001) in patients with a EuroSCORE more than 10. Logistic regression based on different EuroSCORE categories (0-2; 3-5, 6-10,>10), Sco2min-ox, and duration of cardiopulmonary bypass showed that a Sco2min-ox equal or less than 50% is an independent risk factor for 30-day and 1-yr mortality. CONCLUSIONS Preoperative Sco2 levels are reflective of the severity of cardiopulmonary dysfunction, associated with short- and long-term mortality and morbidity, and may add to preoperative risk stratification in patients undergoing cardiac surgery.

The transit of ethanol from blood to breath gas is well characterised. It is used for intraoperative monitoring and in forensic investigations. A further substance, which can be measured in breath gas, is the phenol propofol. After a simultaneous bolus injection, the signals (time course and amplitude) of ethanol and propofol in breath gas were detected by ion molecule reaction-mass spectrometry (IMR-MS) and compared. After approval by the regional authorities, eight pigs were endotracheally intubated after a propofol-free induction with etomidate. Boluses of ethanol (16 mug/kg) and propofol (4 or 2 mg/kg) were infused alone and in combination. For both substances, breath gas concentrations were continuously measured by IMR-MS; the delay time, time to peak and amplitude were determined and compared using non-parametric statistic tests. IMR-MS allows a simultaneous continuous measurement of both substances in breath gas. Ethanol appeared (median delay time, 12 vs 29.5 s) and reached its peak concentration (median time to peak, 45.5 vs 112 s) significantly earlier than propofol. Time courses of ethanol and propofol in breath gas can be simultaneously described with IMR-MS. Differing pharmacological and physicochemical properties of the two substances can explain the earlier appearance and time to peak of ethanol in breath gas compared with propofol.

Aims The aims of this study were (i) to assess the effect of additional urinary ethyl glucuronide (EtG) and ethyl sulphate (EtS) assessment on diagnosed relapse rates in detoxified alcohol-dependent patients; and (ii) to compare dropout rates between EtG- and EtS-negative and -positive patients. Design Two studies on detoxified alcohol-dependent patients. If patients had no indication of relapse they were asked for a urinary sample at discharge from in-patient treatment 3, 6 and 12 weeks after discharge (study 1) and 1, 3 and 6 weeks after discharge (study 2), respectively. Setting Department of Psychiatry, University of Luebeck, Germany. Participants A total of 107 and 32 detoxified alcohol-dependent patients having participated in a 3-week in-patient motivation enhancement programme. Measurement Personal interviews, breathalyzer tests, assessment of urinary EtG and EtS with liquid chromatography-tandem mass spectrometry (LC-MS/MS analysis). Finding Urinary EtG and EtS were always positive at the same time. In the first study 13.5% of the patients were already positive before being discharged from hospital. At the follow-ups 3, 6 and 12 weeks after discharge 12.2, 19.4 and 28.0%, respectively, of the patients coming to the follow-up and denying relapse were positive on urinary EtG and EtS. In the second study, of those patients showing up for follow-up after 1 week and denying relapse, EtG and EtS were positive in four cases (17.4%). Only one EtG- and EtS-positive relapser (3.1%) came to the next follow-ups. In both studies the rates of detected relapses were significantly higher for early follow-ups if urinary EtG and EtS results were considered additionally. Dropout rates until the next follow-up were significantly higher among positive than EtG- and EtS-negative patients. Conclusion Urinary EtG and EtS improve verification of abstinence in studies of alcohol-dependent patients.

BACKGROUND Major depression has been associated with endocrine and immune alterations, in particular a dysregulation of the hypothalamus-pituitary-adrenal system with subsequent hypercortisolism and an imbalance of pro- and anti-inflammatory cytokines. Recent studies suggest that vascular endothelial growth factor (VEGF), a cytokine involved in angiogenesis and neurogenesis, may also be dysregulated during stress and depression. These observations prompted us to examine VEGF and other angiogenic factors in patients with major depressive disorder. METHODS Twelve medication-free female patients with a major depressive episode in the context of borderline personality disorder (MDD/BPD) and twelve healthy women were included. Concentrations of VEGF, VEGF receptors 1 and 2, basic fibroblast growth factor-2 (FGF-2), hepatocyte growth factor (HGF), angiopoetin-2, interleukin-8 (IL-8) and transforming growth factor-beta1 (TGF-beta1) were determined from serum profiles. RESULTS Increased concentrations of VEGF and FGF-2 were found in MDD/BPD patients compared to the healthy comparator group. No group differences were found concerning the other angiogenic factors examined. CONCLUSION Depressive episodes in the context of borderline personality disorder may be accompanied by increased serum concentrations of VEGF and FGF-2. Similar findings have been observed in patients with major depression without a borderline personality disorder. A dysregulation of angiogenic factors may be another facet of the endocrine and immunologic disturbances frequently seen in patients with depressive episodes.

BACKGROUND: The calibration and testing procedures of a pulse oximeter with arterial blood samples from healthy subjects are based on reference values from the hemoximeter. There are no tests to identify the accuracy of the reference devices. Because of this limitation and since the true values of oxygen saturation (sO2 in %) in blood samples were not known, we used the differences between two identical devices, A and B, for error assessment. METHODS: Two identical devices, A and B, from five leading manufacturers were investigated. Seventy-two arterial blood samples from 12 healthy volunteers at three different levels of saturation between 100% and 70% sO2 were randomly evaluated by the test systems. RESULTS: The observed differences (Delta) between Devices A and B, as a measure for the error of the hemoximeters, increased significantly with all manufacturers from level 97 (Deltamin,-0.9%; Deltamax, 2.6%) to 85 (Deltamin,-2.4%; Deltamax, 4.3), this effect was even stronger between levels 97 and 75 (Deltamin,-4.6%; Deltamax, 4.3%). A variance proportion analysis revealed the concentration of the reduced hemoglobin as the main error source for sO2 measurements. Independent from the sO2 levels there were also significant differences for the carboxy hemoglobin concentration in the range of 0%-4% and for the methemoglobin concentration in the range of 0%-1%. CONCLUSIONS: The variance of sO2 measurements between identical devices increased significantly when saturation decreased from the normal level of 97% to the hypoxemic levels of 85% and 75%.

The German Regional Group of EASI was established during the annual Meeting of the German Society of Immunology in Kiel in September 2005. Since this initial informative meeting, an active core group of about a dozen rheumatologists, immunologists, and laboratory specialists has been generating starter projects. In general, these projects do focus on clinically associated diagnostic questions, and do integrate a variety of specialists with profound knowledge in several related subjects. The aims of the German EASI group are to contribute to the definition of standards and to improve patient care. Therefore, the group is establishing guidelines for the diagnosis of autoimmune diseases, to standardize and improve their quality, combining the experience of clinical and laboratory specialists. The diagnostic activities focus currently on systemic lupus erythematosus (SLE) and on rheumatoid arthritis. These activities include laboratory investigations and diagnosis through clinical manifestations. Standardized diagnostics cannot be based solely on vague symptoms and positive laboratory tests. In laboratory diagnostics, standardization and implementation of objective methods for the detection of autoantibodies has been identified as a central challenge. Here, immune fluorescence techniques and the evaluation of RibP are used as first parameters that could improve SLE diagnostics. Furthermore, guidelines and proposals from scientific medical organizations, and in particular from other national EASI groups will be adapted to the German health system. A cornerstone of implementation is the identification and logistic preparation of existing serum banks, the definition of gaps that should be bridged, and, particularly, the definition and collection of adequate control groups. Through these measures, the German EASI group will provide a standardized diagnostic model of autoimmune disorders throughout Europe starting in the field of rheumatology. Diagnostics may become more rational, efficient, faster, and cost-efficient. Patients with autoimmune rheumatic disorders will profit from receiving an earlier and more accurate diagnosis, which again will allow earlier therapeutic intervention and lead to a better long-term clinical outcome.

BACKGROUND In preparation for a study of the pharmacokinetics and elimination of propofol, a frequently used intravenous narcotic, we sought for a simple but accurate method for determining the drug in biological fluids from various mammalian species. MATERIALS AND METHODS We established an isocratic high performance liquid chromatography (HPLC) assay with fluorimetric detection for quantification of propofol, studied the analytical characteristics of the method, and measured the narcotic in heparinized whole blood and corresponding plasma samples drawn from 5 subjects each of humans, pigs, sheep and goats prior to and after 10 minutes of constant infusion of propofol. RESULTS Following protein precipitation with methanol, propofol was quantified in the alcoholic phase. With 30 microl extract, lower limits of detection and quantification of propofol were 2 and 10 microg I(-1), the measurable range extended to 8000 microg I(-1). Intra- and inter-assay CVs tested at propofol concentrations between 40 and 3000 microg I(-1) were < 3% and < 8%, respectively. Propofol levels ranged from 900 to 10,000 microg I(-1) after 10 minutes of drug infusion; among the animals treated with identical doses, pigs exhibited the highest and sheep the lowest circulating propofol concentrations. CONCLUSIONS Analysis of propofol by the HPLC method described is highly practicable, sensitive and specific. Propofol concentrations measured in heparinized blood and corresponding plasma samples differ slightly; in addition to inter-individual variations, species-specific differences in the drug's disposition between plasma and blood cells were observed.

OBJECTIVE: Low bone mineral density has repeatedly been reported in patients with major depressive disorder (MDD), and MDD has been discussed as a risk factor for the development of osteoporosis. MDD in young adults often occurs in the context of borderline personality disorder (BPD), and both MDD and BPD have been associated with a dysregulation of the hypothalamic-pituitary-adrenal system and subsequent hypercortisolemia. To date, it is unclear whether comorbid BPD in depressed patients modulates the extent of bone mass reduction. Therefore, we examined bone density, markers of bone turnover, and proinflammatory cytokines in depressed patients with and without BPD. Patients with BPD alone and healthy women served as comparison groups. METHOD: Twenty-four patients with MDD and 23 patients with comorbid MDD and BPD were included. Sixteen patients with BPD and 20 healthy women of similar body mass index served as the comparison group. BMD was assessed by means of dual-energy x-ray absorptiometry. Markers of bone turnover, endocrine and immune parameters were determined. For data analysis, the group of depressed patients without comorbid BPD was divided according to age into two groups (younger depressed patients with a mean age of 30 years and older patients with a mean age of 42.9 years). RESULTS: BMD at the lumbar spine was significantly reduced in a) depressed women with comorbid BPD (mean age, 28.6 years) and in b) older depressed patients without BPD (mean age, 42.9 years). Osteocalcin, a marker of osteoblastic activity, and crosslaps, a marker of bone loss, were significantly different between the study groups. Tumor necrosis factor-alpha was increased in depressed patients when compared with healthy women. Furthermore, TNF-alpha was positively correlated with serum crosslaps, a marker for osteoclastic activity. CONCLUSION: Depression is associated with reduced bone mass, in particular in patients with comorbid BPD. Possible factors contributing to BMD reduction include endocrine and immune alterations associated with either MDD or BPD. We conclude from our data that a history of MDD with and without comorbid BPD should be considered as a risk factor in clinical assessment instruments for the identification of persons prone to osteoporosis.

OBJECTIVES We evaluated two new autoanalyzers, μTAS and Lumipulse for des-γ-carboxyprothrombin (DCP) assay. MATERIAL AND METHODS Analytical performance was evaluated, and the upper reference limit of the 97.5th percentile for DCP was re-established using sera from 140 healthy individuals. DCP levels were determined by the two autoanalyzers and EIA in a total of 239 sera from HCC patients (n=120) and those without HCC (n=119). RESULTS Total imprecision of the two automated assays was <5% CV. Analytical measurement ranges (AMRs) were verified to be linear. The new reference limits were 29.5 mAU/mL for μTAS and 35.0 mAU/mL for Lumipulse. There were proportional and constant biases between the results from the autoanalyzers and those from EIA. CONCLUSION The two newly developed DCP assays showed high analytical performance, but re-establishment of reference limits would be necessary. The new analyzers could be useful for clinical laboratories because of convenience of operation and wide AMRs.

The administration of hydroxocobalamin (OHCob), alone or with sodium thiosulfate, is a standard therapy for cyanide poisoning. OHCob is a red chromophore, and its interference with co-oximetric and colorimetric laboratory measurements has been evaluated in a few conflicting reports. The interference of OHCob was investigated in samples spiked with 10 different concentrations of OHCob (0-1500 mg/L). The concentration of 73 different analytes was measured using nine different analysers (ABL 800 Flex, Advia 1800, Advia Centaur Xp, Architect ci8200, Immulite 2500, Konelab 30i, Modular Analytics SWA, Synchron LX 20 and Vitros 5.1). All instruments yielded some results that were affected by OHCob at concentrations equivalent to a single therapeutic dose. Of the 73 different analytes, 64% showed interference on at least one instrument. Of all 187 tests performed, 47% were biased with more than 10%. Interference was generally limited to photometric assays, whereas immunological and ion-selective electrode measurements were unaffected. OHCob present in the blood after treatment for cyanide poisoning interfered with many laboratory assays in an unpredictable way, making some results invalid. Some affected tests are important in the treatment of cyanide poisoning. The interference is not solely due to wavelength, but also to chemical interaction. Without delaying the administration of OHCob, blood should, preferably, be drawn in advance, or, at least, the laboratory should be informed about the OHCob treatment. If the laboratory receives OHCob-containing samples, methods and instruments should be selected to minimize bias, and the manufacturer of the OHCob should recommend relevant precautions to customers in the package insert.

BACKGROUND: Last year Abbott Laboratories introduced the ARCHITECT i1000SR modular chemiluminescent immunoassay analyzer for laboratories performing less than 200 test per day. The analyzer has a diverse menu of most routinely tested assays for the low to mid volume hospital laboratory. We evaluated the analytical performance, productivity and efficiency of this system for a one-year period. METHOD: The analytical performance was ascertained by i) determining functional sensitivity in serum matrix for cTnI and measuring precision for other assays. ii) Accuracy was determined by performing patient correlations for TSH, cTnI and FT4 assays. iii)Analyzer productivity and efficiency were evaluated by determining the expected annual throughput and impact of routine workload on STAT TATs, respectively. RESULT: Coefficient of variation ranging from 3.6 to 8.2 % were achieved for all assays evaluated. Functional sensitivity for cTnI was found to be 0.05ng/ml. Patient correlation gave regression coefficients ranging from 0.875 - 0.998. An average hourly throughput ranged from 41 - 48 tests per hour (tph). CONCLUSION: In conclusion, we find the ARCHITECT i1000SR random access immunoassay analyzer to meet all of the requirements desired in a low to mid volume instrument. Stat turn around times (TAT) are maintained to less than 20 minutes.

BACKGROUND A new automated immunoassay low-mid volume (< or = 250 immunoassays/day) chemiluminescent analyzer, Abbott Architect i1000sR, was evaluated by seven laboratories around the world (4 in Europe, one each in Canada, Japan, and the U.S.A.) to demonstrate equivalent performance for key operating characteristics (e.g., precision, turn around time, limit of detection, functional sensitivity, and linearity). METHODS The laboratories followed standard protocols to assess precision, limit of detection (LoD), functional sensitivity, assay linearity, method comparison, and sample carryover. Turn around time for three stat assays (beta-hCG, BNP, and CK-MB) and the time required to complete workloads of 50 and 100 tests with a mixture of 75% routine tests and 25% stat tests was also evaluated. RESULTS Total precision was typically < 5% CV for nine immunoassays. Analytical performance met design goals and demonstrated equivalency to package insert data for assays on market and in use for an existing high volume immunoassay system. Stat turn around times were consistent with the fixed analytical time of 15.6 minutes and met the expectations of the laboratories. Measured test throughput ranged from 47 - 54 tests per hour and demonstrated that the analyzer was fit for the intended purpose of supporting a laboratory that performs < or = 250 immunoassays per day. CONCLUSIONS A multisite, international analyzer familiarization study is a practical means of confirming that a new instrument meets both a manufacturer's design specifications and users' real world expectations and provides a pragmatic test for the system. The experience of investigators at seven sites around the world indicates that a new fully automated chemiluminescent system is suitable for use.

BACKGROUND The analytical performance of the clinical chemistry module c 501 (cobas 6000 analyzer series) was evaluated for therapeutic drug monitoring and drugs of abuse testing using a spectrum of representative assays. Particular attention was paid to potential interactions between reagents using a simulated routine workload. METHODS Within-run and total imprecision were assessed using a selection of representative reagents. Deviation from a consensus mean was tested using samples from a proficiency testing scheme. Method comparison using routine samples was carried out against the MODULAR ANALYTICS SWA and COBAS INTEGRA 800 analysis systems. RESULTS Total coefficients of variation (CV) ranged from 1.9% to 7.8% for individual drugs, and from 3.2% to 8.6% for drugs of abuse testing. Results from proficiency test samples were between 81% and 125% of the consensus mean for therapeutic drugs. Method comparisons (Passing-Bablok regression) showed overall good comparability to MODULAR ANALYTICS SWA and COBAS INTEGRA 800 systems, with slopes from 0.93 to 1.17 and correlation coefficients r > 0.98. Imprecision in a simulated routine run was tested using a total of 42 methods (10 therapeutic drug monitoring, 9 drugs of abuse testing, 3 enzymes, 12 substrates, 8 specific protein assays). Imprecision in the reference batch run ranged from 0.7% to 5.0% CV for therapeutic drug monitoring assays, except for digoxin (DIG)(7.3%), and from 0.9% to 7.7% for drugs of abuse testing. The CVs of general clinical chemistry and specific protein tests were within the expected limits of 2% and 4%. CV changes in the simulated routine run were within the expected limits for most assays. Negative DeltaCVs (> or = 2%) for DIG, digitoxin (DIGIT), cannabinoids (THC), and phencyclidine (PCP) may indicate improved performance when running these assays in a simulated routine operation. A positive DeltaCV (> or = 3%) was found for amphetamines (AMPHs). CONCLUSIONS In conclusion, the cobas c 501 module seems to be well-suited for routine use as consolidated workstation. Except for a potential interaction with AMPH, as indicated by the positive DeltaCV, no significant interferences from different reagents could be observed during this study.

BACKGROUND Integrated systems that combine clinical chemistry and immunoassay analyzers are used routinely. Sample to sample carryover is an inherent risk and can cause erroneously high patient test results for immunoassays. IVD manufacturers and laboratories must be aware of this phenomenon and guard against it. METHODS We used a sample carryover protocol that directs the clinical chemistry module to process samples with very high immunoassay analyte concentrations followed by samples with very low concentrations for the same analyte. Low concentration samples were then tested by the immunoassay module to determine if the clinical chemistry module caused primary sample tube to primary sample tube carryover of the immunoassay analyte. RESULTS Sample carryover was assessed on the Abbott ci8200 for HBsAg, AFP, beta-hCG, and PSA. Observed HBsAg carryover met the design specification of <0.1 ppm. Carryover for the other analytes was <0.1 ppm or below the assay limit of detection. CONCLUSIONS IVD manufacturers must design integrated systems to minimize primary specimen tube carryover and avoid analytical laboratory error that can impact patient safety. Carryover testing is difficult for clinical laboratories to perform in order to verify system performance. Laboratories must consider the potential for specimen carryover and its impact on results whether moving primary sample tubes between separate analyzers or using an integrated system.

Background: Preanalytical factors are the main source of variation in clinical chemistry testing and among the major determinants of preanalytical variability, sample hemolysis can exert a strong influence on result reliability. Hemolytic samples are a rather common and unfavorable occurrence in laboratory practice, as they are often considered unsuitable for routine testing due to biological and analytical interference. However, definitive indications on the analytical and clinical management of hemolyzed specimens are currently lacking. Therefore, the present investigation evaluated the influence of in vitro blood cell lysis on routine clinical chemistry testing. Methods: Nine aliquots, prepared by serial dilutions of homologous hemolyzed samples collected from 12 different subjects and containing a final concentration of serum hemoglobin ranging from 0 to 20.6 g/L, were tested for the most common clinical chemistry analytes. Lysis was achieved by subjecting whole blood to an overnight freeze-thaw cycle. Results: Hemolysis interference appeared to be approximately linearly dependent on the final concentration of blood-cell lysate in the specimen. This generated a consistent trend towards overestimation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, creatine kinase (CK), iron, lactate dehydrogenase (LDH), lipase, magnesium, phosphorus, potassium and urea, whereas mean values of albumin, alkaline phosphatase (ALP), chloride, gamma-glutamyltransferase (GGT), glucose and sodium were substantially decreased. Clinically meaningful variations of AST, chloride, LDH, potassium and sodium were observed in specimens displaying mild or almost undetectable hemolysis by visual inspection (serum hemoglobin <0.6 g/L). The rather heterogeneous and unpredictable response to hemolysis observed for several parameters prevented the adoption of reliable statistic corrective measures for results on the basis of the degree of hemolysis. Conclusion: If hemolysis and blood cell lysis result from an in vitro cause, we suggest that the most convenient corrective solution might be quantification of free hemoglobin, alerting the clinicians and sample recollection.

BACKGROUND Recently, hemoglobin A1c (HgbA1c), microalbumin (MA), C-reactive protein (CRP) and rheumatoid factor (RF) have been introduced on high throughput general chemistry system. We evaluated analytical performance of these assays on an integrated clinical chemistry and immunoassay analyzer and studied the impact of testing these assays on these systems on the overall efficiency of the analyzer, via computer simulation. METHODS The analytical performance was measured by determining precision, linearity and correlation of patient sample results with in-house testing methodology. MedModel simulation software is used to develop simulation model and process efficiency is determined by measuring turnaround times and resource utilization. RESULTS Between-days CVs ranged from 8.59% for MA to 3.22% for HgbA1c level 1 controls. Less than 2% carryover for all 4 methods was observed on the integrated analyzer. For HgbA1c on HPLC analyzer, the minimum and maximum TAT for a batch of 50 samples was 3.78 and 160 min, respectively, while for the integrated system it was 28.2 and 35.1 min, respectively. Labor utilization for the 2 processes ranged from 3.21% to 3.75%. CONCLUSION Chemistry module on an integrated system can be used to determine the HgbA1c and other serum proteins.

BACKGROUND: The Architect ci8200 is an integrated serum analyzer for photometric, electrochemical and immunological assays. Several assays of each category and the workflow performance of the system were compared with established laboratory procedures in two laboratories. METHODS: Measurements were compared with the ELECSYS 2010 (Roche Diagnostics) for CEA, PSA, FPSA, AFP, folate, vitamin B12, with the CENTAUR (Bayer) for TSH, T4, FT4, FSH and Estradiol, with the LIAISON (DiaSorin) for TSH, FT4 and FT3, with the Behring Nephelometer BN II (Dade-Behring) for ferritin, and with the INTEGRA 800 (Roche Diagnostics), and the AU640 (Olympus) for clinical chemistry assays. Workflow studies were performed to compare times of analysis required for defined analytical workloads. RESULTS: The coefficients of variation (CVs) for within-run imprecision were between 3% and 6% for CEA, PSA, FPSA, AFP and ferritin, and between 3% and 11% for TSH, FT4, FT3, folate and vitamin B12. The CVs for day-to-day imprecision for immunoassays were between 3% and 10%, except for vitamin B12 (CVs 11-13%) and FT4 (CV 10%-13%). For clinical chemistry tests corresponding CVs for within-run imprecision were < 1%, except for HDL, triglyceride, creatinine, ALT, LD and lipase (CVs<2%) and bicarbonate (CV 3%-6%) and magnesium (CV < 3%). The CVs for day-to-day imprecision for clinical chemistry tests were < 1%, except for sodium, CO(2), magnesium, phosphorus, glucose, uric acid, HDL, triglyceride, ALT, AST CK, lipase with CVs < 6% and for CO(2)<11%. Dilutional linearity testing of seven immunoassays and five clinical chemistry analytes resulted in recovery rates of 90-110%. Correlation studies with 15 immunoassays and 25 clinical chemistry tests showed acceptable agreements with established methods. Work flow analyses demonstrated a net gain in time of analysis up to 109 min depending on the size of the sample batch analyzed with the Architect ci8200 as the main analyzer as compared to the currently installed routine laboratory equipment. Median turn-around times were 7 and 30 min for chemistry assays and immunoassays, respectively, when ordered as STAT analyses, and 18 min when chemistry assays were ordered as routine determinations. CONCLUSIONS: Assays on the Architect ci8200 performed well, fulfilling quality control requirements as defined for instance by German quality control guidelines (RiliBAK). Method comparisons showed acceptable agreements with established assays. Workflow studies using the Architect ci8200 documented shorter times of analyses as compared with the conventionally established laboratory routine demonstrating the potential of integrated chemistry/immunoassay analyzers to provide faster and more efficient performance.

New biological materials and advances in robotic and computer technologies have enabled the development of automated systems designed for high-performance infectious disease immunoassays and nucleic acid amplification. The fully automated, random access Bayer ADVIA Centaur immunoassay system, offering testing for fertility, therapeutic drug monitoring, infectious disease, allergy, cardiovascular, anemia, oncology, TDMs and thyroid, has been specifically designed for use in large-volume laboratories. New immunoassay tests have been developed for the ADVIA Centaur for the hepatitis A virus, hepatitis B virus, hepatitis C virus and HIV. These assays have undergone extensive performance evaluation using samples designated in the CTS in support of obtaining the Communautés Européennes (CE) mark for European market distribution. The ADVIA Centaur Immunoassay System represents an optimal platform for infectious disease testing because of its flexibility in allowing many different assay formats and protocols with multiple incubation steps and washes coupled with its combination of magnetic particle separation and chemiluminescent detection. Additional quality features of the system design are the sample integrity verification/check, the use of disposable sample pipette tips, clot detection, the ability for sensing liquid levels, the reagent aspiration verification/check, the automatic cascade reflex testing, repeat testing, and automated reagent inventory. The ADVIA Centaur has a maximum test throughput of 240 tests per hour. Minimal hands-on time is required as a result of the large onboard capacity for reagents and supplies combined with automated maintenance and monitoring features, which streamline operations and result in a walk-away through-put of up to 840 tests.