Evaluation of the Beckman Synchron CX4 clinical chemistry analyzer in a hospital laboratory

The Beckman Synchron CX4 random-access multianalyzer was evaluated in a medium sized hospital laboratory. The instrument does end-point, rate, and multipoint assays and carries on-board reagents for 24 tests. In addition to predefined tests, the instrument can be programmed for 100 user-defined tests; these are stored on the hard disk and can utilize up to three component reagents each. The throughput is 200 tests per hour. There is stat testing capability. In our evaluation, within-run and between-run precision and linearity were good, and no reagent carryover was detected. There was good correlation with the in-house methodology for the 19 tests evaluated. A disadvantage at the time of evaluation was interference by elevated bilirubin on creatinine, phosphorus, uric acid, and triglycerides. This problem of interference is being addressed by the manufacturer.     

Beckman CX5、日立7170S两系统测定结果校正的探讨

目的 探讨Beckman CX5和日立7170S全自动生化分析仪五项酶测定结果一致性的方法。方法 分别使用定标液、质控品和病人的新鲜混合血清为材料，通过增加校正因子，共同校正Beckman CX5和日立7170S两系统测定结果。结果 实验表明，Beckman CX5和日立7170S两系统经过校正，对比测定病人的混合血清，再增加校正因子，使两系统五项酶类测定结果保持高度一致性。结论 由于条件所限，不能实现仪器、试剂、定标质控三统一的情况下，可以通过增加校正因子实现Beckman CX5和日立7170S两系统五项酶测定结果的一致性，能满足临床的需要。     

小儿急性轮状病毒肠炎的电解质渗透压与阴离子间隙分析

目的　探讨小儿急性轮状病毒肠炎的电解质、渗透压和阴离子间隙 (AG)的变化情况以及相互间的关系。方法　 6 2例患儿均在治疗前作血清Na 、K 、Cl-、CO2 CP和渗透压的测定。AG按Na - (Cl- HCO-3 )计算。所有患儿均采用ELISA方法检测大便轮状病毒抗原。结果　代谢性酸中毒 (简称代酸 )、血钠低于正常 (<135mmol/L)、高氯血症和低钾血症 ,分别为 87 1%、45 2、41 9%和 38 7%。酸中毒随脱水程度的加重而加重 (χ2 =10 47,P <0 0 0 5 )。渗透压以低渗为多 6 6 1% ,等渗次之 2 9% ,高渗仅 4 8%。低渗性脱水 34例 ,其血Na 均值为 132 0 3mmol/L ,但与总体均数相一致 (t=2 0 ,P >0 0 5 )。AG正常、增高和降低分别为 5 6 5 %、38 7%和 4 8% ,平均水平是 14 48± 5 39mmol/L。AG与血Na 呈正相关 ,AG水平随脱水程度的加重而升高 (t=2 872 ,P <0 0 1)且随脱水性质的加大而上升 (F =13 473,P <0 0 1)。临床诊断代酸 5 4例 ,其中高AG组2 3例 ,正常AG组 2 9例 ,低AG组 2例 ,三组代酸发生率无显著性差异 (χ2 =2 5 6 7,P >0 0 5 )。结论　电解质紊乱及酸碱失衡以低钠、低钾、高氯及代酸多见。渗透压以低渗为多 ,若以血钠来判断低渗压 ,建议以 <135mmol/L为宜。AG增高对代酸的诊断优于HCO-3 的降低。     

User-defined serum aspartate and alanine aminotransferase, cholesterol, triglycerides, urea, and uric acid for the Beckman synchron CX 4/5 using Ames Sera-Pak reagents.

Beckman aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol, triglycerides, urea, and uric acid Liquid Reagents for Synchron CX 4/5 (48, 48, 25, 60, 26, and 30 cents US/test, respectively) are expensive. We have established our own methods for serum AST, ALT, cholesterol, triglycerides, urea, and uric acid (6, 6, 5, 12, 13, and 6 cents US/test, respectively) using Ames Sera-Pak reagents. Linearity of our AST, ALT, cholesterol, triglycerides, urea, and uric acid methods were either similar to or higher than the Beckman methods. The within run and day-to-day run precisions were acceptable. Recovery of our AST, ALT, cholesterol, triglycerides, urea, and uric acid were excellent. Our results for AST, ALT, cholesterol, triglycerides, urea, and uric acid correlated well with the Beckman results. Bilirubin (340.8 mumol/L) did not significantly interfere on our AST, ALT, cholesterol, triglycerides, and urea, while its concentrations of 165.8 mumol/L started giving negative interference on uric acid. Turbidity (2+) did not interfere significantly on our AST and ALT but started giving positive interference on cholesterol, triglycerides, urea, and uric acid. Hemolysis (2+) gave positive interference on our cholesterol, triglycerides, urea, and uric acid. Stability of Ames Sera-Pak working reagents was at least 30 days for AST, ALT, urea, and uric acid and 40 days for cholesterol and triglycerides.     

"可波动的误差参照标准"结果和意义—附Beckman CX9型生化分析仪函变质控稳定性与实用性论证

针对自动化仪器在稳定的函数变化率（简称函变）因素条件下，可因不同质量控制物的测定变异或随机差异而存在不同的可波动的误差，导致不同质控规则的不同质控性能特征的影响，提出选择标准物质来作为可波动的误差参照标准的简便、实用方法，既能适应临床高效检验的要求，达到一体化质控性能特征，又能为室内质控（IQC）增收节支降低各成本。     

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.     

Update on value of the anion gap in clinical diagnosis and laboratory evaluation

Anion gap (AG) is a calculated value commonly used in clinical practice. It approximates the difference between the concentration of unmeasured anions (UA) and unmeasured cations (UC) in serum. At present, the reference range of anion gap has been lowered from 8-16 to 3-11 mmol/l because of the changes in technique for measuring electrolyte. However, clinicians and textbooks still refer and use the old reference value of 8-16 mmol/l. This may lead to misinterpretation of the value of anion gap. Our study updated the value of anion gap in clinical diagnosis and laboratory evaluation. Criteria for using anion gap were also suggested. We analyzed serum electrolyte using the Beckman Synchron CX5. The anion gap was calculated from the formula: [Na(+)-(Cl(-)+HCO(3)(-))]. We estimated the reference range using the non-parametric percentile estimation method. The reference range of anion gap obtained from 124 healthy volunteers was 5-12 mmol/l, which was low and confirmed the reports from other studies (3-11 mmol/l) using ion-selective electrode. From the retrospective study on the 6868 sets of serum electrolyte among hospitalized patients, we found the incidences of normal, increased, and decreased anion gaps were 59.5%, 37.6%, and 2.9%, respectively. The mean and central 90% range of increased anion gap were 16 and 13-20 mmol/l, which was lower than those reported in previous study (25 and 19-28 mmol/l). Anion gap exceeding 24 mmol/l was rare. The mean and central 90% range of decreased anion gap were 3 and 2-4 mmol/l, which were lower than those reported in previous study (6 and 3-8 mmol/l). The value of less than 2 mmol/l was rare. The most common causes of increased anion gap (hypertensive disease, chronic renal failure, malignant neoplasms, diabetes mellitus and heart diseases) and decreased anion gap (liver cirrhosis and nephrotic syndrome) in this study were similar to those in previous studies. We found two cases of IgG multiple myeloma with anion gap of 2 mmol/l. In conclusion, clinicians and laboratorians can use the anion gap as clue in quality control. They can check the incidences of increased and decreased anion gap. If one finds high incidence of increased anion gap (>24 mmol/l) or decreased anion gap (<2 mmol/l), one should check the quality control of electrolyte and whether the patients were hypoalbuminemia or hyperglobulinemia. An anion gap exceeding 24 mmol/l will suggest the presence of metabolic acidosis. It is very rare to find anion gap with the negative sign.     

忻州地区健康成人血清总蛋白、清蛋白及清蛋白/球蛋白比值的参考范围调查

目的 了解并建立忻州地区健康成人血清总蛋白(TP)、清蛋白(ALB)以及清蛋白/球蛋白比值(A/G)的参考范围.方法 对2008年10月至2011年12月间来该院检查的4 014例健康成人血清总蛋白(TP)、清蛋白(ALB)进行测定,并计算A/G比值;对检测结果进行统计分析,计算参考值范围.结果 该地成人血清总蛋白(TP)、清蛋白(ALB)及A/G比值的平均值分别为71.51 g/L、43.66 g/L和1.60;参考范围分别为:TP(59.96～83.06)g/L,ALB(36.91～50.41)g/L,A/G(1.11～2.09);不同性别、不同年龄段人群之间血清TP、ALB、A/G水平存在不同程度的差异.结论 不同地区人群的血清总蛋白、清蛋白及A/G比值水平也不尽相同,各地区、实验室应建立当地不同性别、不同年龄段的参考范围,以供临床对检验结果的诊断作出正确判断.     

Multicenter evaluation of the interference of hemoglobin, bilirubin and lipids on Synchron LX-20 assays.

The influence of interference by hemolysis, icterus and lipemia on the results of routine chemistries may lead to wrong interpretations. The H-, I- and L-indices that can be measured by the Beckman LX-20 instrument (Beckman Coulter) in serum or plasma samples are a reliable semi-quantitative measure of the size of these interferences. A survey carried out in 16 Dutch clinical laboratories on the use of these indices demonstrated that in several of these laboratories, the influence of interferences is largely underestimated. Therefore, a multicenter study was carried out in which we examined the interference of hemolysis, icterus and lipemia on 32 analytes. On the basis of biological variation, we decided on cutoff indices above which analytically significant interference exists. We found analytically significant interference by hemolysis, icterus or lipemia, in 12, 7 and 15 of the 32 analytes studied, respectively. Flagging of results on the basis of analytically significant interference, however, results in too many clinically insignificant comments. On the basis of clinical significance, we conclude that significant interference by hemolysis, icterus or lipemia is present in only 5, 6 and 12 of the analytes studied, respectively. Use of the cutoff indices presented here facilitates optimal use of the LX-20 indices to prevent reporting of wrong results due to interference.     

含有机酸的阴离子间隙计算公式与酸碱平衡关系的研究

目的通过建立含有机酸的阴离子间隙测定公式,研究该项指标在代谢性酸中毒的诊断价值。方法把原来只含有Na~ 、HCO_3~-、Cl~-的阴离子间隙计算公式加上乳酸、β-羟丁酸、乙酰乙酸和无机磷的计算公式,分别测定128例正常人及代谢性酸中毒患者104例阴离子间隙,并进行比较。结果使用公式AG_4在诊断肾功不全代谢性酸中毒灵敏度为66．1%,使用AG_1 AG_2诊断酮症酸中毒灵敏度为93．7%,使用AG,诊断乳酸性酸中毒灵敏度为56．5%。结论使用含有有机酸的阴离子计算公式对诊断代谢性酸中毒患者具有较高的灵敏度。     

Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human organic anion transporter 3, organic anion transporting polypeptide 4C1, and multidrug resistance P-glycoprotein

Sitagliptin, a selective dipeptidyl peptidase 4 inhibitor recently approved for the treatment of type 2 diabetes, is excreted into the urine via active tubular secretion and glomerular filtration in humans. In this report, we demonstrate that sitagliptin is transported by human organic anion transporter hOAT3 (Km=162 microM), organic anion transporting polypeptide OATP4C1, and multidrug resistance (MDR) P-glycoprotein (Pgp), but not by human organic cation transporter 2 hOCT2, hOAT1, oligopeptide transporter hPEPT1, OATP2B1, and the multidrug resistance proteins MRP2 and MRP4. Our studies suggested that hOAT3, OATP4C1, and MDR1 Pgp might play a role in transporting sitagliptin into and out of renal proximal tubule cells, respectively. Sitagliptin did not inhibit hOAT1-mediated cidofovir uptake, but it showed weak inhibition of hOAT3-mediated cimetidine uptake (IC50=160 microM). hOAT3-mediated sitagliptin uptake was inhibited by probenecid, ibuprofen, furosemide, fenofibric acid, quinapril, indapamide, and cimetidine with IC50 values of 5.6, 3.7, 1.7, 2.2, 6.2, 11, and 79 microM, respectively. Sitagliptin did not inhibit Pgp-mediated transport of digoxin, verapamil, ritonavir, quinidine, and vinblastine. Cyclosporine A significantly inhibited Pgp-mediated transport of sitagliptin (IC50=1 microM). Our data indicate that sitagliptin is unlikely to be a perpetrator of drug-drug interactions with Pgp, hOAT1, or hOAT3 substrates at clinically relevant concentrations. Renal secretion of sitagliptin could be inhibited if coadministered with OAT3 inhibitors such as probenecid. However, the magnitude of interactions should be low, and the effects may not be clinically meaningful, due to the high safety margin of sitagliptin.     

A critical evaluation of the Beckman Coulter Access hsTnI: Analytical performance,reference interval and concordance

IntroductionWe investigated the analytical performance, outlier rate, carryover and reference interval of the Beckman Coulter Access hsTnI in detail and compared it with historical and other commercial assays.Materials and methodsWe compared the imprecision, detection capability, analytical sensitivity, outlier rate and carryover against two previous Access AccuTnI assay versions. We established the reference interval with stored samples from a previous study and compared the concordances and variances with the Access AccuTnI+3 as well as with two commercial assays.ResultsThe Access hsTnI had excellent analytical sensitivity with the calibration slope 5.6 times steeper than the Access AccuTnI+3. The detection capability was markedly improved with the SD of the blank 0.18–0.20 ng/L, LoB 0.29–0.33 ng/L and LoD 0.58–0.69 ng/L. All the reference interval samples had a result above the LoB value. At a mean concentration of 2.83 ng/L the SD was 0.28 ng/L (CV 9.8%). Carryover (0.005%) and outlier (0.046%) rates were similar to the Access AccuTnI+3. The combined male and female 99th percentile reference interval was 18.2 ng/L (90% CI 13.2–21.1 ng/L). Concordance amongst the assays was poor with only 16.7%, 19.6% and 15.2% of samples identified by all 4 assays as above the 99th, 97.5th and 95th percentiles. Analytical imprecision was a minor contributor to the observed variances between assays.ConclusionThe Beckman Coulter Access hsTnI assay has excellent analytical sensitivity and precision characteristics close to zero. This allows cTnI measurement in all healthy individuals and the capability to identify numerically small differences between serial samples as statistically significant. Concordance in healthy individuals remains poor amongst assays.     

Reference ranges for serial measurements of blood velocity and pulsatility index at the intra-abdominal portion, and fetal and placental ends of the umbilical artery.

OBJECTIVE: To construct reference ranges for serial measurements of umbilical artery (UA) blood flow velocity and pulsatility index (PI) at standardized insonation sites during the second half of pregnancy. METHODS: This was a prospective longitudinal study of the umbilical circulation. UA blood flow velocities were measured at the intra-abdominal portion, fetal end and placental end at 4-weekly intervals at 19-42 weeks of gestation in 130 low-risk singleton pregnancies. A total of 513 observations were used to construct the reference ranges using regression statistics and multilevel modeling. RESULTS: UA blood velocities and PI were higher at the intra-abdominal portion and fetal end than at the placental end. The gestational age-related increase of end-diastolic velocity was greater than the corresponding increase of the peak systolic velocity at all locations. The mean differences (delta values) of UA blood velocities between the fetal and placental ends increased and that of PI decreased with advancing gestational age. CONCLUSION: UA Doppler parameters vary significantly at different locations. We have established new reference ranges for the UA velocities and PI at standardized locations based on longitudinal observations, which should be useful for the surveillance of fetuses with repeated observations.     

Macroprolactin, big-prolactin and potential effects on the misdiagnosis of hyperprolactinemia using the Beckman Coulter Access Prolactin assay

OBJECTIVE: To examine whether use of the Beckman Coulter Access Prolactin (PRL) assay, which has low reactivity with macro-PRL, obviates the need for screening hyperprolactinemic samples. DESIGN AND METHODS: Samples from 1020 hyperprolactinemic individuals and 401 healthy volunteers were treated with polyethylene glycol (PEG). Macro-PRL was assessed from (1) percent PRL recovery, using cut-off values derived by gel filtration chromatography (GFC) and (2) significant (p<0.05) normalisation of PRL following PEG. RESULTS: PRL recovery was similar in volunteer and hyperprolactinemic samples (mean+/-SD 101+/-13% and 101+/-19%, respectively). In hyperprolactinemic samples, macro-PRL was identified from PRL recovery in 9.7%, although levels were moderate to high in only 3.9%. The total PRL normalised following PEG in 7.4%. Correlations of PRL recovery with the proportions of macro-, big- and monomeric PRL following GFC (n=30 samples, range of PRL and macro-PRL levels) were -0.89, -0.20 and 0.92, respectively. The big-PRL content was 0-28%. Regression analysis suggested that PEG precipitated both macro-PRL and big-PRL. CONCLUSIONS: Using the Access assay, macro-PRL can cause apparent hyperprolactinemia and big-PRL may cause misclassification of individuals. Screening using PEG is applicable to assays with low macro-PRL reactivity provided specific reference values are derived.     

Renal tubular action of prostaglandin E2 on water and electrolyte excretion in the nonanesthetized chicken

The tubular effects of prostaglandin (PG) E2 on electrolyte and water excretion were investigated in vitro in the nonanesthetized chicken by the Sperber technique. This technique allowed the administration of PGE2 directly into the peritubular space of one kidney by way of the venous portal circulation. When compared to the contralateral, noninfused kidney, PGE2 in the infused kidney (0.6-4.5 X 10(-10) mol/kg X min) induced a dose-dependent increase in urinary flow rate, a mild natriuresis and kaliuresis, with a concomitant decrease in urinary osmolality and an increase in free-water clearance. These effects occurred without changes in renal plasma flow or glomerular filtration rate. PGA2 (1.7-7.8 X 10(-10) mol/kg X min), another vasodepressor PG, did not modify electrolyte excretion. The tubular handling of PGE2 was observed by following the administration of [3H]PGE2. [3H] PGE2 was metabolized extensively during its renal tubular excretion. The 3H label was secreted actively into the urine by the organic anion transport system which was inhibited by novobiocin. Inhibition of the organic anion transport system did not modify the renal tubular effects of PGE2 on electrolyte and water excretion. These results indicate that PGE2 exerts a tubular inhibitory effect on sodium and water excretion, this action being located on the peritubular side.     

In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes

OBJECTIVES: Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Single-time point phenotypic metabolic ratios were used to determine whether long-term supplementation of goldenseal ( Hydrastis canadensis ), black cohosh ( Cimicifuga racemosa ), kava kava ( Piper methysticum ), or valerian ( Valeriana officinalis ) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4/5 activity. METHODS: Twelve healthy volunteers (6 women) were randomly assigned to receive goldenseal, black cohosh, kava kava, or valerian for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam and caffeine, followed 24 hours later by chlorzoxazone and debrisoquin (INN, debrisoquine), were administered before (baseline) and at the end of supplementation. Presupplementation and postsupplementation phenotypic trait measurements were determined for CYP3A4/5, CYP1A2, CYP2E1, and CYP2D6 by use of 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin urinary recovery ratios (8-hour collection), respectively. The content of purported "active" phytochemicals was determined for each supplement. RESULTS: Comparisons of presupplementation and postsupplementation phenotypic ratio means revealed significant inhibition (approximately 40%) of CYP2D6 (difference, -0.228; 95% confidence interval [CI], -0.268 to -0.188) and CYP3A4/5 (difference, -1.501; 95% CI, -1.840 to -1.163) activity for goldenseal. Kava produced significant reductions (approximately 40%) in CYP2E1 only (difference, -0.192; 95% CI, -0.325 to -0.060). Black cohosh also exhibited statistically significant inhibition of CYP2D6 (difference, -0.046; 95% CI, -0.085 to -0.007), but the magnitude of the effect (approximately 7%) did not appear to be clinically relevant. No significant changes in phenotypic ratios were observed for valerian. CONCLUSIONS: Botanical supplements containing goldenseal strongly inhibited CYP2D6 and CYP3A4/5 activity in vivo, whereas kava inhibited CYP2E1 and black cohosh weakly inhibited CYP2D6. Accordingly, serious adverse interactions may result from the concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 and CYP3A4/5 substrates. Kava kava and black cohosh may interact with CYP2E1 and CYP2D6 substrates, respectively. Valerian appears to be less likely to produce CYP-mediated herb-drug interactions.