Synchron LX Research Articles

Interference of ascorbic acid with chemical analytes

Ascorbic acid can interfere with methodologies involving redox reactions, while comprehensive studies on main chemistry analysers have not been reported. We therefore attempted to determine the interference of ascorbic acid with analytes on the Beckman Synchron LX20. Various concentrations of ascorbic acid were added to serum, and the serum analytes were measured on the LX20. With a serum ascorbic acid concentration of 12.0 mmol/L, the values for sodium, potassium, calcium and creatinine increased by 43%, 58%, 103% and 26%, respectively (P<0.01). With a serum ascorbic acid concentration of 12.0 mmol/L, the values for chloride, total bilirubin and uric acid decreased by 33%, 62% and 83%, respectively (P<0.01), and were undetectable for total cholesterol, triglyceride, ammonia and lactate. There was no definite influence of ascorbic acid on analytical values for total CO(2), urea, glucose, phosphate, total protein, albumin, amylase, creatine kinase, creatine kinase-MB, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total iron, unbound iron-binding capacity or magnesium. Ascorbic acid causes a false increase in sodium, potassium, calcium and creatinine results and a false decrease in chloride, total bilirubin, uric acid, total cholesterol, triglyceride, ammonia and lactate results.

Aggravation of Anti-Myeloperoxidase Antibody-Induced Glomerulonephritis by Bacterial Lipopolysaccharide: Role of Tumor Necrosis Factor-α

Aggravation of Anti-Myeloperoxidase Antibody-Induced Glomerulonephritis by Bacterial Lipopolysaccharide: Role of Tumor Necrosis Factor-α

Phosphatidylinositol increases HDL-C levels in humans

Studies have shown that phosphatidylinositol (PI) can stimulate reverse cholesterol transport by enhancing the flux of cholesterol into HDL and by promoting the transport of high density lipoprotein-cholesterol (HDL-C) to the liver and bile. The goal of this study was to determine the safety and therapeutic value of PI after oral administration to normolipidemic human subjects. We performed a randomized 2 week study in 16 normolipidemic subjects. Subjects received either 2.8 or 5.6 g of PI, with or without food. PI was well tolerated by all subjects. PI significantly affected the levels of HDL-C and triglyceride in the plasma of subjects receiving PI with food. The lower dose showed a 13% increase in HDL-C, whereas the high dose showed an increase of 18% over the 2 week period. Both low- and high-dose groups showed significant increases in plasma apolipoprotein A-I. The high dose of PI also decreased plasma triglycerides by 36% in the fed subjects. These data suggest that after only 2 weeks, PI may have a comparable therapeutic value to niacin, with negligible side effects.

Vitamin C and aberrant electrolyte results

Vitamin C interferes with assays involving the redox-reaction. However, the interference of Vitamin C with electrolytes has not been reported. In the present case, we describe a 61-year-old lady with severe electrolyte abnormalities after administration of high doses of vitamin C. This patient, who had terminal colon cancer, presented to hospital with anuria. Her electrolytes were extremely abnormal (determined on the Beckman Synchron LX20): serum sodium 200 mmol/L, potassium 7.0 mmol/L, and chloride 50 mmol/L. Repeated measurements showed similar abnormalities. However, these critical abnormalities did not fit her clinical picture, as she was alert with normal vital signs. One of the specimens was also run on both the ABL700 and the Bayer644 analyzers, and the electrolytes appeared normal. Pooled serum from healthy individuals to which various amounts of vitamin C was added then was analyzed on Beckman Synchron LX20 for electrolytes, demonstrating the interference of vitamin C consistent with the initial finding. Thus, we eventually figured out that the aberrant results were due to the vitamin C caused analytical interference.

Rapid Detection of Oleander Poisoning Using Digoxin Immunoassays

Oleander is an ornamental shrub that grows in the United States, Australia, India, Sri Lanka, China, and other parts of the world. All parts of the plant are poisonous because the presence of cardiac glycoside oleandrin. Despite its toxicity, oleander extract is used in folk medicines. Because of its structural similarity, oleandrin cross-reacts with the fluorescence polarization immunoassay (FPIA) for digoxin. We studied the potential of detecting oleandrin in serum using 5 common digoxin immunoassays (FPIA, MEIA, both from Abbott; Beckman digoxin assay on Synchron LX, Chemiluminescent assay, CLIA from Bayer Diagnostics) and a recently FDA-approved turbidimetric assay on the ADVIA 1650 analyzer (Bayer). Aliquots of drug-free and digoxin-like immunoreactive substances (DLIS)-free serum pools were supplemented with ethanol extract of oleander leaves or oleandrin (Sigma Chemicals) in amounts expected in vivo after severe overdose. We observed significant apparent digoxin concentration with FPIA, Beckman, and the new turbidimetric assay (1 mL drug-free serum supplemented with 5.0 microL of oleander extract: apparent digoxin 2.36 ng/mL by the FPIA, 0.32 ng/mL by the MEIA, 0.93 ng/mL by the Beckman, 0.82 ng/mL by the new turbidimetric assay). The CLIA showed no cross-reactivity. Similar observations were made when serum pools were supplemented with oleandrin. Because cross reactivity should be tested in the presence of the primary analyte, we supplemented serum pools prepared from patients receiving digoxin with oleander extract or oleandrin. The measured digoxin concentrations were falsely elevated with the FPIA, Beckman, and turbidimetric assays, the highest false elevation being observed with the FPIA. Surprisingly, apparent digoxin concentrations were falsely lowered when MEIA was used. Digibind neutralizes free apparent digoxin concentration in vitro in serum pools supplemented with oleander extract, and this effect can be measured by the FPIA. We conclude that FPIA is most sensitive to detect the presence of oleander in serum. In contrast, the CLIA (no cross-reactivity) should be used for monitoring digoxin in a patient receiving digoxin and self-medicated with a herbal remedy containing oleander.

Interference in Measurement of Potassium Caused by Bacterial Contamination of an Analyzer

We encountered a problem with potassium measurement after periods of standby on a Beckman Synchron LX20 Pro. Initial potassium measurements were rejected because of excessive reference drift, and potassium results for quality-control (QC) samples were as much as 2.5 mmol/L above the previous mean. Replicate analyses of control material immediately after standby revealed a decreasing trend in potassium concentration, whereas simultaneously determined electrolytes did not. When the analyzer had not been in standby, no such problems were seen. We recorded the voltage from the analog-to-digital converter (ADC) during 10 replicate measurements of QC material immediately after an 8-h standby (Fig 1A⇓ ). The reference voltages increased progressively, whereas the potassium voltages did not. Because the difference between the sample and reference is used to calculate the potassium concentration, the reported potassium concentration decreased progressively (Fig. 1A⇓ ). Figure 1. Results …

The EMIT 2000 tacrolimus assay: an application protocol for the Beckman Synchron LX20 PRO analyzer

Objective: To develop and evaluate the performance of an application protocol for the EMIT 2000 tacrolimus (Tac) assay on the Beckman Synchron LX20 PRO Analyzer. Design and Methods: Precision, accuracy, linearity, and lower limit of quantitation were investigated. Specimens from 212 kidney, liver, heart/heart–lung, and islet cell transplant patients were analyzed and results were compared to those from the Abbott MEIA II assay. A separate population of 232 specimens was coanalyzed by the enzyme-multiplied immunoassay technique (EMIT) assay and liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: Total imprecision was 13.7% and 6.0% at concentrations of 3.4 and 19.1 μg/L, respectively. Recoveries from assayed reference materials ranged from 103% to 109%. A quantitation range of 3.2–30.0 μg/L was validated. The EMIT assay on the LX20 PRO analyzer showed an average negative bias of 1% compared to the MEIA assay and an average positive bias of 17% compared to LC-MS/MS. Conclusion: This application for the EMIT 2000 Tac assay on the Beckman Synchron LX20 PRO analyzer enhances the versatility of the immunoassay for routine therapeutic drug monitoring (TDM) of this immunosuppressant in the clinical setting.

Effects of beta thalassemia minor on results of six glycated hemoglobin methods

Background Beta-thalassemia minor (BTM) is a common benign condition that can be present in patients with diabetes mellitus. There are conflicting reports about the effect of BTM on glycated hemoglobin (gHb) measurements. We evaluated 6 gHb methods using samples from non-diabetic subjects with BTM. Methods Samples submitted for hemoglobin phenotype analysis were evaluated. A total of 57 samples (30 controls and 27 with BTM) from non-diabetic subjects were selected. GHb analysis was performed by Tosoh A1c 2.2+, Primus CLC 330, Bayer DCA 2000, Beckman Coulter, Synchron CX7 and LX20, and Roche Tina-quant II assays. Results The A1c 2.2+, CLC 330, DCA 2000 and Tina-quant II assays showed no statistically significant difference between the control and BTM groups. In contrast, BTM results were significantly higher than controls on the Synchron CX7 analyzer and borderline significant on the Synchron LX20 ( p=0.051). Further investigation demonstrated an increase in Synchron %HbA 1c results with decreasing hemoglobin concentrations. Conclusions In this study using samples from subjects with normal or near-normal gHb, BTM does not affect gHb measurements per se. However, the Synchron methods yielded higher results for samples with lower hemoglobin concentrations, like those that can be seen in BTM. The Synchron method was improved at the end of 2003, which minimized this problem.

Analytical performance of the Synchron LX®20 Pro, BN™II and IMMAGE® high sensitivity C-reactive protein assays and concordance in cardiovascular risk stratification

Background: C-reactive protein (CRP) can provide valuable prognostic information for risk of cardiovascular events. Several automated high sensitivity CRP immunoassays are currently available for risk assessment. Methods: The analytical performance of the Synchron LX®20 Pro, BN™II and IMMAGE® high sensitivity CRP assays were evaluated and concordance within cardiovascular risk tertiles was examined for 529 serum samples. Results: All three assays exhibited satisfactory between-run imprecision based on CVs≤9.0% over a wide range of CRP concentrations. The LX20 Pro and BN II were linear over an extensive measuring range, whereas the IMMAGE exhibited a slight deviation from linearity producing results with a positive bias at CRP levels between 0.7 and 2.6 mg/l. Moderately hemolyzed samples interfered with the LX20 Pro and IMMAGE CRP assays, whereas moderate lipemia interfered with the BN II. Correlation studies revealed that the LX20 Pro and IMMAGE produced results 8.2% lower and 5.1% lower, respectively, compared with the BN II. There was good agreement among methods for cardiovascular risk assessment. Conclusions: All three CRP assays exhibited acceptable analytical performance for cardiovascular risk assessment. Although results by the LX20 Pro and IMMAGE were lower than the BN II, there was good agreement within each cardiovascular risk assessment tertile.

Artifactual Undetectable HDL-Cholesterol with the Beckman Synchron LX and Vitros 950 Assays Temporally Associated with a Paraprotein

We report here the failure of the Synchron LX (Beckman) and Vitros 950 (Johnson & Johnson) assays to detect HDL-cholesterol (HDL-C) in the presence of a paraprotein. HDL-C was repeatedly undetectable (<50 mg/L) in a male who historically had HDL-C values in the 600–800 mg/L range, as determined by manual dextran sulfate precipitation followed by measurement of HDL-C on a BMC (Roche) Hitachi 747, during a time period that coincided with a change in laboratory HDL-C test methodology to the Synchron LX HDL-C (Beckman). The specimens with undetectable HDL-C values in the Synchron LX assay were not hemolyzed or icteric, two conditions known to decrease HDL-C values in the Synchron LX assay. A review of laboratory test results for this patient at the most recent visit for which his HDL-C was undetectable revealed a newly identified paraprotein (IgGκ; Table 1⇓ , specimen 1a) and a new diagnosis of multiple myeloma. View this table: Table 1. Panel of paraprotein-containing specimens tested for HDL-C by the Synchron LX (Beckman) and Vitros 950 (Johnson & Johnson) assays1. HDL-C …

Use of fluorescence polarization immunoassay for salicylate to avoid positive/negative interference by bilirubin in the Trinder salicylate assay.

Significant positive bias of bilirubin in the Trinder salicylate method on automated analysers has been reported. Because the fluorescence polarization immunoassay (FPIA) for salicylate is also widely used in the clinical laboratory, we studied the potential interference of bilirubin in the salicylate FPIA. Salicylate serum pools (three different pools) were prepared from patients receiving salicylate. We also prepared a normal serum pool containing no salicylate and serum pools containing no salicylate but elevated bilirubin. Aliquots of one salicylate pool were supplemented with various concentrations of bilirubin (42.8- 427.5 micro mol/L) and salicylate concentrations were measured by the salicylate FPIA (TDxFLx and AxSYM analysers). We also assayed these specimens with the Trinder salicylate method, using both Synchron LX and Hitachi 917 analysers for comparison with the results obtained by the FPIA method. In another experiment, aliquots of the two other salicylate pools were supplemented with various concentrations of bilirubin (42.8-684.0 micro mol/L) in order to further study the effect of very high bilirubin concentrations on the salicylate FPIA. We also added known amounts of salicylate to serum pools containing elevated bilirubin but no salicylate and measured salicylate using the FPIA in order to study the recovery of salicylate in the presence of elevated bilirubin concentrations. The FPIA showed minimal interference from bilirubin. We also observed good recovery of salicylate when specimens high in bilirubin but containing no salicylate were supplemented with known amounts of salicylate and the FPIA was used for the measurement of salicylate concentration. However, we observed falsely low salicylate concentrations with the Trinder method using the Synchron LX (primary wavelength 560 nm, secondary wavelength 700 nm) analyser and falsely increased salicylate concentrations using the same reagent but the Hitachi 917 (primary wavelength 546 nm, no secondary wavelength) analyser in the presence of elevated bilirubin levels compared with the FPIA results. We conclude that the FPIA for salicylate is not affected by high bilirubin concentrations up to 427.5 micro mol/L.

Effect of the traditional Chinese medicines Chan Su, Lu-Shen-Wan, Dan Shen, and Asian ginseng on serum digoxin measurement by Tina-quant (Roche) and Synchron LX system (Beckman) digoxin immunoassays.

Chan Su, Lu-Shen-Wan, Dan Shen, and Asian ginseng are traditionally used to treat a number of conditions, including cardiovascular disease. All of these traditional Chinese medicines exhibit cardioactive properties. Digoxin is a cardioactive drug with a narrow therapeutic range (0.8-1.9 ng/mL). A patient taking digoxin may also take these Chinese medicines for their cardiotonic effects. Moreover, the active components of these medicines that are responsible for cardiotonic effects bear structural similarities to digoxin. Therefore, we studied the potential interference of these Chinese medicines with two digoxin immunoassays--the Tina-quant (Roche Diagnostics) and the Beckman (Synchron LX system)--and compared the values with the fluorescence polarization immunoassay (FPIA; Abbott Laboratories). When very small amounts (2-5 microL) of aqueous extract of Chan Su or Lu-Shen-Wan were added to drug-free serum, we observed high digoxin-like immunoreactivity with the FPIA. In contrast, when ethyl acetate extract of Dan Shen or microliter amounts of ginseng extract were added to drug-free serum, we observed modest digoxin-like immunoreactivity with the FPIA, but no apparent digoxin activity with the Roche and Beckman digoxin immunoassays. When aliquots of a digoxin pool prepared from patients receiving digoxin were supplemented with these Chinese medicines, we observed the most significant interference with the FPIA. The presence of endogenous digoxin-like immunoreactive substances can have additive effects with these Chinese medicines and falsely increase apparent digoxin levels by the FPIA. On the other hand, the Roche and Beckman assays were free from interference from DLIS but showed significant interference from Chan Su and Lu-Shen-Wan. We conclude that the FPIA showed the most significant interference from all four of the Chinese medicines we studied. However, the Roche and Beckman assays showed no interference from two (Dan Shen and Asian ginseng) of the four Chinese medicines we studied.

High-Sensitivity C-Reactive Protein Methods Examined

Because C-reactive protein (CRP) has prognostic value in patients with acute coronary syndromes and in apparently healthy people (1), various high-sensitivity CRP (hs-CRP) methods have been introduced (2)(3). For the clinical laboratory, it is of course most practical if one CRP method can be used for the complete measuring range (0.2–1000 mg/L) to report reliable CRP results regardless of the clinical context. We report here the evaluation of a hs-CRP method for the Beckman Coulter IMMAGE®, which is compared with the IMMULITE and BNA hs-CRP methods, as well as with the Beckman Synchron LX®20 CRP method for the higher range. Venous blood samples were collected from 291 ostensibly healthy blood donors, 177 males and 114 females presenting at the Sanguin Blood Bank in Maastricht. Samples for method comparison were collected from 531 patients for whom a CRP was requested for routine analysis. The Medical Ethical Committee of the Hospital approved the procedure followed. Serum was separated from the red cells by centrifugation at 2500 g for 20 min and stored at −70 °C until analysis (4). The hs-CRP detection method on the IMMULITE automated analyzer (Diagnostic Product Corporation) is a two-site chemiluminescent enzyme immunometric assay with a detection limit of 0.10 mg/L and a measuring range of 0.10–500 mg/L. hs-CRP analysis is performed on the BNA nephelometer (Dade Behring) by particle-enhanced immunonephelometry with a detection limit of 0.18 mg/L and a measuring range of 0.18–1150 mg/L. The IMMAGE hs-CRP (trade name, IMMAGE CRPH; Beckman Coulter) is a turbidimetric method based on the peak rate principle (2) measured by a near-infrared particle immunoassay, with a laser diode at 940 nm, a detection limit of 0.20 mg/L, and a measuring range of 0.20–1440 mg/L. To improve sensitivity, the latex particle size is now increased three- …

Novel test and its automation for the determination of erythrocyte acetylcholinesterase and its application to organophosphate exposure

Background: Because of the lack of a problem-free, reliable method for determination of erythrocyte acetylcholinesterase (AChE), we developed a simple kinetic method, which we found to be both reliable and suitable for automation in the routine clinical laboratory. Methods: Acetylthiocholine, used as substrate, is hydrolysed by acetylcholinesterase to yield acetate and thiocholine. Thiocholine reacts with dichlorophenolindophenol, a blue coloured compound, which is reduced to a colourless product, producing a linear decrease in absorption at 606 nm. If required, this assay can also be run at 600 nm with equally acceptable results. Results: The method was automated on the Synchron LX20 multianalyser (Beckman Instruments) and blood samples of 80 patients with clinically symptomatic organophosphate poisoning and 153 normal controls were evaluated. Acetylcholinesterase values were in the range of 0–14 U gHb −1 in cases of organophosphate poisoning, in contrast with normal controls, who had AChE values of 24.4–37.9 U gHb −1. No overlap was found between AChE values of controls and poisoned cases. Intra- and inter-assay coefficients of variation were 1.68 and 3.71%, respectively. Conclusion: The method we propose for measurement of AChE was found to be simple, reliable and easily automatable in the routine clinical laboratory.