Volume 44, Issue 7

During the past two decades, flow-cytometric immunophenotyping of lymphocytes has evolved from a research technique into a routine laboratory diagnostic test. Extensive studies in healthy individuals resulted in detailed age-related reference values for different lymphocyte subpopulations in peripheral blood. This is an important tool for the diagnosis of hematological and immunological disorders. Similar, albeit less detailed, information is now available for other lymphoid organs, e.g., normal bone marrow, lymph nodes, tonsils, thymus and spleen. Flow-cytometric immunophenotyping forms the basis of modern classification of acute and chronic leukemias and is increasingly applied for initial diagnostic work-up of non-Hodgkin's lymphomas. Finally, with multiparameter flow cytometry, it is now possible to identify routinely and reliably low numbers of leukemia and lymphoma cells (minimal residual disease). Clin Chem Lab Med 2006;44:775–96.

Clinical laboratory errors can be considered as either belonging to attribute or continuous variables. Attribute errors are usually considered to be pre- or post-analytical errors, whereas continuous variable errors are analytical. Goals for each error type are different. Error goals for continuous variables are often specified as limits that contain 95% of the results, whereas attribute error goals are specified as allowed error rates for serious events. This leads to a discrepancy, because for a million results, there can be up to 50,000 medically unacceptable analytical errors, but allowable pre- and post-analytical error rates are much lower than 5%. Steps to remedy this are to classify analytical error rates into severity categories, exemplified by existing glucose error grids. The results in each error grid zone are then counted, as has been recommended by the Food and Drug Administration (FDA). This in effect transforms the continuous variable errors into attribute errors. This is an improvement over current practices for analytical errors, whereby the use of uncertainty intervals is recommended that include only 95% of the results (i.e., leaves out the worst 5%), and it is precisely this 5% of results that are likely to be in the most severe zones of an error grid. Clin Chem Lab Med 2006;44:797–8.

Background: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein-cholesterol (LDL-C) concentrations, which frequently gives rise to premature coronary artery disease. The clinical expression of FH is highly variable, even in patients carrying the same LDL receptor ( LDLR ) gene mutation. This variability may be due to environmental and other genetic factors. Methods: We investigated paraoxonase 2 ( PON 2 ) Ser311Cys, lipoprotein lipase ( LPL ) Asn291Ser, plasminogen activator inhibitor-1 ( PAI-1 ) T11053G, β-fibrinogen ( FGB ) −455 G>A and nitric oxide synthase gene ( NOS ) −922 A>G polymorphisms in 84 patients with FH. The effect of polymorphisms as independent factors of high lipid values was evaluated. Results: The PON 2 Cys311 allele was correlated with high total cholesterol and LDL-C and apolipoprotein B levels, while LPL Asn291 , PAI-1 T11053 , FGB –455 G and NOS –922 A alleles were correlated with high apolipoprotein B levels. Conclusions: These results suggest that apolipoprotein B levels in FH heterozygotes may be affected by several different genetic variants. Clin Chem Lab Med 2006;44:799–806.

Background : A genetic association/prospective follow-up study was conducted to investigate whether genetic variation of the α 2B -adrenergic receptor gene was associated with the risk of restenosis in 96 Greek coronary artery disease patients undergoing coronary angioplasty and stent implantation. Methods : For comparison of genotype frequency, a control group of 83 asymptomatic individuals was also studied. The end-point of the current study was the incidence of restenosis at 7 months of clinical follow-up. Results : The majority of patients (70/96) had the insertion/insertion genotype, fewer patients (23/96) had the insertion/deletion genotype and only 3/96 had the deletion/deletion genotype; overall the frequency distribution was not different from that of the control subjects. Restenosis occurred in 15 of the 96 patients. Conclusions : In the population studied, α 2B -adrenoreceptor polymorphisms were not found to predispose patients to an increased incidence of restenosis. Nevertheless, these findings should be considered as preliminary, taking into account the small number of patients that were studied and the rarity of the deletion/deletion genotype. Clin Chem Lab Med 2006;44:807–12.

Background: Elevated plasma homocysteine levels are associated with increased risk of vascular disease and of congestive heart failure (CHF), with a relationship between homocysteine values and disease severity. Hyperhomocysteinemia is a risk factor for cardiac dysfunction. In this study, the predictive value of elevated homocysteine levels was investigated in the prognosis of ischemic and non-ischemic CHF. Methods: A total of 159 patients with CHF, 89 with non-ischemic and 70 with ischemic CHF (83% males, mean age 62years, mean ejection fraction 27%), and 119 controls (79% males, mean age 59.8years) had fasting blood samples taken to measure plasma homocysteine, vitamin B 12 and folate levels. Coronary angiography was performed for all patients. The mean duration of follow-up was 49.6±36.7months. Results: As in other studies, the mean level of homocysteinemia was significantly higher in the CHF group (15.80μmol/L) than in the control group (10.90μmol/L) (p=0.001) whatever the etiology (non-ischemic, 16.11±6.84μmol/L; ischemic, 15.41±6.45μmol/L). This result was observed without vitamin deficiency, but in patients, the mean creatinine value was moderately higher than in controls. We found a positive correlation between plasma homocysteine levels and New York Heart Association (NYHA) classification, creatinine and age. Moreover, hyperhomocysteinemia appears to be a powerful predictive factor of mortality in CHF patients (relative risk of death, 4.23; p=0.0003). In the follow-up of this study, 41.5% of patients with homocysteinemia >17μmol/L died vs. 21.3% of patients with levels <17μmol/L. In multivariate analysis, when homocysteine levels were adjusted for a second parameter (age, NYHA, creatinine, diabetes), the risk of death remained significant after each adjustment. Conclusions: Elevated homocysteine levels observed in CHF patients, whatever the etiology of their heart disease (ischemic or non-ischemic), were correlated with the severity of the disease. Hyperhomocysteinemia appears to be a predictive factor of mortality in CHF patients. Clin Chem Lab Med 2006;44:813–6.

Background : Impaired insulin secretion (IS) and insulin resistance (IR) play an essential role in the pathogenesis of type 2 diabetes mellitus. Several simplifying indices were developed that calculate IS and/or IR from venous insulin and glucose concentrations. The aim of the present study was to compare these indices with each other and with regard to their efficiency to differentiate between non-diseased and diabetic glucose tolerance states. Methods : Oral glucose tolerance tests were performed in 301 subjects. The study group was divided into five groups according to WHO/American Diabetes Association (ADA) cut-off values: apparently normotolerant, diabetic, isolated 2-h post-challenge hyperglycemic, isolated fasting hyperglycemic and intermediate groups. The minimal error rate (diagnostic non-efficiency) indicating a misclassification of a diabetic tolerance state was determined for 12 indices. Results : The error rate was lower than 15% for the index of Cederholm and Wibell and for the indices of Stumvoll et al. The misclassification rates for the other indices (index of Matsuda and de Fronzo, index of Myllynen et al., HOMA IR, HOMA β-cell, FIRI, QUICKI, index of McAuley and insulinogenic index) were 20–27%; however, the diagnostic sensitivity was close to a 1:1 chance of a correct decision. The hypothesis that isolated post-prandial hyperglycemia (IPH) and isolated fasting hyperglycemia (IFH) differ in their insulin sensitivity and insulin response could not be supported by the present results. Conclusions : The indices of Cederholm and Wibell and of Stumvoll et al. were found to be appropriate as diagnostic indicators of the pathogenesis of diabetic glucose tolerance and were more closely related to the glucose tolerance state than the other indices. Clin Chem Lab Med 2006;44:817–23.

Background : In order to be able to take preventative measures early in life against the development of atherosclerosis, it is important to evaluate profiles of subclinical atherosclerosis, especially among young adults. Methods : We screened plasma homocysteine levels, highly sensitive C-reactive protein levels and carotid intima-media thickness in young and elderly adults. Results : Among both young and elderly adults, plasma homocysteine and highly sensitive C-reactive protein were significantly lower in females than in males. Highly sensitive C-reactive protein was significantly lower in young adults than in elderly adults, and homocysteine was lower (but not significantly) in young adults than in elderly adults. Among young adults, mean carotid intima-media thickness was lower (but not significantly) in females than in males. Among elderly adults, mean carotid intima-media thickness was significantly lower in females than in males. Among both males and females, mean carotid intima-media thickness was significantly higher in elderly adults than in young adults. Conclusions : These results demonstrate basic profiles of atherosclerosis markers in young and elderly Japanese adults. Further study is needed to evaluate measures developed for application in early adulthood to prevent atherosclerosis. Clin Chem Lab Med 2006;44:824–9.

There is growing evidence that adiponectin, an adipocytokine with anti-inflammatory and antiathero-genic properties, is involved in the development of atherosclerosis. The aim of the present study was to examine whether serum levels of adiponectin were associated with symptomatic atherosclerotic peripheral arterial disease (PAD). Serum concentrations of adiponectin were measured in 433 patients with symptomatic PAD and 433 controls from the Linz Peripheral Arterial Disease (LIPAD) study. Cases and controls were matched for age, sex and diabetes mellitus. The median serum level of adiponectin was significantly lower in PAD patients than in control subjects (9.5 vs. 10.8mg/L; p=0.014). After adjustment for several possible confounding variables using multivariable logistic regression, odds ratios for symptomatic PAD were 0.95 (95% CI, 0.64–1.42; p=0.080) and 0.59 (95% CI, 0.36–0.97; p=0.037) in the second and third tertiles for adiponectin serum concentrations, respectively, compared with the first tertile. Low serum levels of adiponectin were associated with the presence of symptomatic atherosclerotic PAD, independent of traditional and non-traditional risk factors, suggesting that hypoadiponectinemia may be a marker for systemic atherosclerotic disease. Clin Chem Lab Med 2006;44:830–3.

We measured the concentrations of cardiac troponin T (cTnT) and amino-terminal pro-natriuretic peptide (NT-proBNP) in umbilical cord blood during the second trimester (20–25weeks of gestation) and at delivery in 109 uncomplicated pregnancies to define reference values. Using the 97.5th percentile, the upper reference limits for cTnT and NT-proBNP were 0.308ng/mL and 5402pg/mL in fetuses in the second trimester, and 0.038ng/mL and 1690pg/mL in healthy neonates, respectively. We also evaluated whether labor and delivery mode affected the concentrations of the two analytes. We found significantly higher (p<0.001) umbilical blood NT-proBNP and cTnT levels at 20–25weeks of gestation than at term. In addition, within the term group, NT-proBNP concentrations were significantly higher in women delivering by elective cesarean section than in women delivering spontaneously (p<0.001), and higher than in women delivering by cesarean section during active labor. This indicates that the decrease in NT-proBNP levels is probably due to labor rather than delivery mode. Finally, we confirmed the at-birth reference values previously established for cTnT and NT-proBNP. Clin Chem Lab Med 2006;44:834–6.

Background: It has been proposed that only anti-thyroid-peroxidase (TPOAb) and not anti-thyroglobulin (TgAb) antibodies should be assayed in the diagnosis of autoimmune thyroid disease (AITD). Methods: We analyzed the thyroid autoantibody profile with a multiplex bead array system, which allows simultaneous measurement of thyroid autoantibodies (FIDIS, BioMedical Diagnostics, Marne La Vallée, France). A total of 151 AITD patients (111 Hashimoto's thyroiditis and 40 Graves' disease) and 414 control patients were recruited to the study. Results: The diagnostic sensitivity of TPOAb was greater than that of TgAb in both Hashimoto's thyroiditis (91.9% vs. 82.5%) and Graves' disease (82.5% and 52.5%, respectively), whereas the diagnostic specificity was similar (92.7% for TPOAb and 92.4% for TgAb). Conclusions: The presence of isolated positivity for TgAb in 6% of the Hashimoto's thyroiditis patients indicates that the use of only the TPOAb test does not guarantee sufficient diagnostic sensitivity. In the light of recent findings relating to the pathogenetic role of TgAb and TPOAb in Hashimoto's thyroiditis, knowledge of the autoantibody profile could allow the identification of sub-groups of patients with a different degree of activation of the thyroid autoimmune process. Clin Chem Lab Med 2006;44:837–42.

Background : The activity and isoenzyme composition of N-acetyl-β-D-hexosaminidase (EC.3.2.1.52) in seminal plasma of fertile and infertile men have been evaluated. However, no data are available on the isoenzyme content in seminal plasma from patients with secretory azoospermia. Methods : The activity and isoenzyme composition of seminal plasma from 15 normozoospermic controls and 18 patients with secretory azoospermia were determined by fluorimetric methods. 4-Methylumbelliferil-2-acetamido-2-deoxy-β-D-glucopyranoside and 4-methylumbelliferil-2-acetamido-2-deoxy-β-D-glucopyranoside-6-sulfate were used as fluorigenic substrates. Receiver-operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficiency of the assays. Results : No significant difference was found in total enzyme activity between the two groups, while isoenzyme A activity was significantly lower (p=0.004) and the ratio between total enzyme activity and isoenzyme A activity was significantly higher (p=0.04) in azoospermic patients compared to controls. The diagnostic efficiency of these evaluations was low (≤75.7%). Conclusions : Our findings show that the isoenzyme composition of N-acetyl-β-D-hexosaminidase in seminal plasma from patients with secretory azoospermia is significantly different from controls, but this difference does not represent a useful marker of secretory azoospermia. The fluorimetric assays are simple and rapid methods for evaluating the isoenzyme composition. Clin Chem Lab Med 2006;44:843–7.

Modification of proteins by non-enzymatic glycation is one of the underlying factors known to play a major role in the pathogenesis of many clinical disorders. Glycation of plasma proteins is enhanced by elevated glucose concentrations. However, increased fructosamine has been documented in rheumatoid arthritis patients without any history of diabetes. Collective evidence reveals that malondialdehyde and reduced glutathione can modulate the glycation process. This study was undertaken to unravel the possible association of malondialdehyde and glutathione with fructosamine in rheumatoid arthritis patients. A case-control study was performed on 15 rheumatoid arthritis patients and 15 control subjects. Whole blood glutathione, plasma malondialdehyde, fructosamine and fasting glucose were analyzed in both groups. Partial correlation analysis was performed to predict the independent association of malondialdehyde, glutathione and fasting glucose on fructosamine. In rheumatoid arthritis patients, while fructosamine and malondialdehyde levels were significantly increased, glutathione levels were significantly decreased compared with controls. With partial correlation analysis, fructosamine was found to have a significant positive correlation with malondialdehyde and a negative correlation with glutathione. These data suggest that plasma fructosamine levels are closely associated with malondialdehyde and glutathione in rheumatoid arthritis patients, warranting extra precaution in interpreting fructosamine as a measure of glycemic control in these patients. Clin Chem Lab Med 2006;44:848–52.

Background : There is a need for consensus concerning universal methodological criteria for detection of suboptimal response to acetylsalicylic acid (ASA) therapy. Therefore, animal models to test for ASA effectiveness remain of interest. Our objective was to verify the usefulness of multiparametric whole-blood impedance aggregometry and thromboxane A 2 generation, which are the most popular techniques used for monitoring of ASA treatment effectiveness. Methods : Using multiparametric analysis of whole-blood impedance aggregometry, we examined which parameters of platelet aggregation or disaggregation allow for the best discrimination between ASA-treated (4 or 40mg/kg for 60days) and non-treated male rats. The effectiveness of ASA-mediated inhibition of platelet cyclooxygenase-1 was verified by determination of plasma thromboxane B 2 and urine 11-dehydro-thromboxane B 2 , accepted as reference assays for monitoring of ASA-mediated platelet cyclooxygenase-1 inhibition. Results : Two of the platelet agonists used, collagen (1mg/L) and arachidonic acid (0.5mmol/L), allowed discrimination of control and ASA-treated animals, whereas adenosine diphosphate (5μmol/L) was not effective. It is noteworthy that only ASA-mediated changes in duration of the rising phase for platelet aggregation and the area under the curve for collagen-induced aggregation allowed significant discrimination between low and high ASA dose and remained correlated with the reference parameter, plasma thromboxane B 2 . Conclusions : Analysis of aggregation curves, routinely based only on the amplitude and rate of platelet aggregation, may not be enough discriminative to distinguish between varying ASA doses and treatment schedules. Clin Chem Lab Med 2006;44:853–62.

Background: Elevated plasma homocysteine (Hcy) concentrations are associated with increased risk of systemic vascular diseases, Alzheimer's disease and vascular dementia. Several cross-sectional reports and two prospective clinical studies have recently reported elevated plasma Hcy levels in L-dopa-treated Parkinson's disease (PD) patients and Hcy has been proposed as a possible mediator for the development of long-term L-dopa motor complications (such as wearing off and on-off phenomena, and dyskinesias). The aim of the study was to elucidate a possible role of L-dopa-related hyperhomocysteinemia in the development of dyskinesias. Methods: In this cross-sectional study we compared Hcy, B 12 and folate levels in 53 PD patients treated with L-dopa (29 with dyskinesias, 24 without dyskinesias). Results: Mean plasma Hcy levels were higher in the group of PD patients with dyskinesias (19 vs. 15.4 T: 2.12; p=0.04). After taking into account potential confounding factors, analysis of the data revealed that the occurrence of dyskinesias progressively increased with plasma Hcy levels (relative risk 1.2, 95% CI 1.015–1.4; p=0.03). Conclusions: Our results raise the possibility that Hcy plays a role in the development of dyskinesias, through its toxic effects on both dopaminergic neurons and non-substantia nigra, non-dopaminergic neurons. Clin Chem Lab Med 2006;44:863–6.

In the present study we used patient data to calculate laboratory-specific indirect reference intervals. These values were compared with reference intervals obtained for a healthy group according to recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine and manufacturer suggestions. Laboratory results (422,919 records) from all subjects of 18–45years of age over a 1-year period were retrieved from our laboratory information system and indirect reference intervals for 40 common analytes were estimated using a modified Bhattacharya procedure. Indirect reference intervals for most of the biochemical analytes were comparable, with small differences in lower [alkaline phosphatase (ALP) (male), alanine aminotransferase (ALT), creatine kinase, iron (male), total iron-binding capacity, folic acid, calcium (female), lactate dehydrogenase (LDH), lipoprotein (a) [Lp(a)], thyroid-stimulating hormone (TSH), total triiodothyronine (T 3 ), direct bilirubin, apolipoprotein A-I (apoA-I), glucose, homocysteine, total cholesterol, ferritin, total protein, ceruloplasmin, sodium, blood urea nitrogen (BUN) and uric acid (female)] and/or upper limits [albumin, ALP (male), amylase, apoA-I, creatine kinase-MB (CK-MB), total iron-binding capacity, phosphorus, glucose, total cholesterol, γ-glutamyltransferase (γ-GT), magnesium, total protein, high-density lipoprotein cholesterol (HDL-C), total T 3 , ALP (male), ALT, aspartate aminotransferase (AST) (male), direct bilirubin (male), creatine kinase, iron, folic acid (female), Lp(a), uric acid and triglycerides], to the reference intervals determined for healthy subjects in our laboratory. The indirect reference intervals, with the exception of a few parameters (creatinine, direct total bilirubin, calcium, BUN and potassium), were not similar to the reference intervals suggested by the manufacturers. We conclude that laboratory-specific reference intervals can be determined from stored data with a relatively easy and inexpensive method. Indirect reference intervals derived from stored data may be particularly suitable for the evaluation of results for the presenting population. Clin Chem Lab Med 2006;44:867–76.

Background : It has been advocated that measuring the haemoglobin concentration in a haemolysed sample can be used to correct the potassium concentration. However, estimation of the degree of potassium adjustment has not been validated with patient-derived data. This study aimed to ascertain the relationship between haemolysis and potassium increment using patient samples. Methods : A total of 35 hospital patients (16 male, 19 female; median age 73years, inter-quartile range 45–83years) for whom haemolysed samples were repeated within 24h were included in the study. The difference between potassium in the haemolysed and non-haemolysed repeat sample was correlated with the serum haemolysis index measured on a Beckman Synchron LX20PRO. Results : The linear relationship derived for patient samples showed a potassium increase of approximately 0.16mmol/L for each increment in the haemolysis index. However, Bland-Altman statistics in the patient-derived model showed the variability (95% limit of agreement) in predicted potassium concentration to be ±0.4mmol/L. Conclusions : The magnitude of the relationship using authentic patient data with the Beckman LX20PRO haemolysis index is in keeping with previously described relationships. Use of the haemolysis index on the Beckman LX20PRO to predict potassium concentration in haemolysed samples is not sufficiently accurate to obviate the need for repeat analysis, but can be used to prioritise the need for urgent repeat analysis. Clin Chem Lab Med 2006;44:877–9.

The aim of this study was to investigate the longitudinal changes in serum paraoxonase-1 (PON1) activity from preconception throughout normal pregnancy and their relationships with maternal dietary vitamin C and E intake. The study was performed in 35 women (studied at preconception, at 8, 20 and 32weeks of pregnancy, and at labour). PON1 activity decreased significantly from 145.8 (109.8–198.8) U/L at preconception to 111.1 (85.3–179.9) U/L (p<0.01) at 32weeks and 100.4 (54.7–171.4) U/L (p<0.001) at labour. There was a direct association between vitamin C intake and PON1 at week 32 (p=0.018). We conclude that adequate vitamin C intake in pregnant women may merit consideration, since vitamin C supplementation has proved beneficial in the prevention of preeclampsia in women at increased risk of this condition. Clin Chem Lab Med 2006;44:880–2.

During a normal menstrual cycle, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone can vary widely between cycles for the same woman, as well as between different woman. Reliable reference values based on the local population are important for correct interpretation of laboratory results. The purpose of our study was to determine detailed reference values for these hormones throughout the menstrual cycle using the Abbott ARCHITECT system. From 20 volunteers (age 20–36years) with normal cycles and no use of oral contraceptives, samples were taken every day during their cycle. Volunteers received three vaginal ultrasound examinations (days 10 and 13, and 1 or 2days after ovulation) to measure follicular and corpus luteum development. Hormone levels were measured using the corresponding ARCHITECT assay and were synchronized to the LH peak. Median, and 5th and 95th percentile values were determined for each day of the cycle, as well as for early follicular (days −15 to −6), late follicular (days −5 to −1), LH peak (day 0), early luteal (+1 to +4), mid-luteal (days +5 to +9), and late luteal (days +10 to +14) phases of the cycle. Based on our data, we were able to establish detailed reference values for LH, FSH, estradiol, and progesterone, which should aid in the interpretation of results for these reproductive hormones in a variety of circumstances. Clin Chem Lab Med 2006;44:883–7.

Background : In this study the analytical performance of eight glucose point-of-care testing (POCT) devices was evaluated. For this purpose, POCT measurement of glucose in heparinized blood collected from patients was paralleled by determination of the glucose concentration in the respective plasma by an analyzer (Hitachi 917) in the central laboratory, providing traceable results. Methods : Trueness of POCT measurements was studied by comparing the plasma POCT values (mean of five measurements) with the results from the traceable measurement procedure (TMP). Results : The percentage of POCT results within ±6% of the TMP mean value ranged from 24% to 50%, depending on the POCT device. Within the reference interval of plasma glucose (4.4–6.0mmol/L), up to 67% of the POCT values were lower than 4.4mmol/L, leading to a false diagnosis of hypoglycemia. In the hypoglycemic range (<4.4mmol/L) up to 29% of the POCT analyses were false normoglycemic. Conclusions : In conclusion, this study shows an insufficient trueness of glucose measurements by POCT devices in the normo- and hypoglycemic range. To improve quality assessment, sample splitting and simultaneous measurement of blood glucose concentration every 4weeks by POCT devices and of plasma glucose concentration by a reliable TMP is recommended. Clin Chem Lab Med 2006;44:888–93.

The present paper describes an evaluation of the interferences found with an immunochemical drug test performed during a workplace control. During the period 1993–2003 more than 200,000 urine samples from workers were examined by the Italian Air Force. Samples were screened for drugs of abuse (opiates, cocaine, cannabinoids, amphetamines, methadone) using an immunochemical technique (Roche, kinetic interaction of microparticles in solution, KIMS). A total of 520 positive samples were sent to the Forensic Toxicology Laboratory for confirmation by gas chromatography/mass spectrometry (GC/MS). Approximately 39% of these were found to be true positives. For the remaining samples, pharmacological therapy in subjects was estimated to evaluate possible interferences due to medicine intake. Our study showed a high frequency of false-positive results with this immunochemical technique, mainly for the cannabinoid and amphetamine groups. Recurrent references to some medicines during subject anamnesis were noted. Clin Chem Lab Med 2006;44;894–7.

Background : Rapid technological progress in point-of-care testing allows the measurement of multiple analytes in whole-blood samples. The present study evaluated biosensor-based methods for the measurement of electrolytes and substrates in whole blood using a Stat Profile Critical Care Xpress (Nova Biomedical, Waltham, MA, USA) multiprofile analyzer and their comparability with standard laboratory methods. Because of the increased utilization of arterial blood samples in hospitalized patients and limited information on differences between arterial and venous blood for most routine laboratory tests, analytical differences caused by different sample types were evaluated. Methods : Whole-blood arterial samples and venous serum samples were obtained from 70 random patients with a variety of diagnoses admitted to the intensive care unit. The Stat Profile Critical Care Xpress analyzer was used to obtain whole-blood electrolyte and substrate profiles. For comparison studies, plasma or serum samples were analyzed according to standard laboratory methods using an Olympus AU 600 analyzer (Olympus Mishima, Shizuoka, Japan). Results : Imprecision, expressed as the coefficient of variation (CV%), was less than 5.7% for all analytes at both high and low concentrations, except for creatinine, with a CV of 13.8% for low and 9.5% for high concentrations. The inaccuracy of electrolyte and substrate measurements in whole blood using a Stat Profile Critical Care Xpress analyzer met the analytical quality specification required for near patient testing, with observed bias within the range −4.5% to 5.3%. Statistically significant correlation (p<0.05) was obtained between standard laboratory methods performed on arterial plasma or venous serum samples on an Olympus AU 600 analyzer and direct whole-blood measurements on the Stat Profile Critical Care Xpress point-of-care analyzer for all parameters tested, although slope and intercept values showed analytical differences for electrolyte measurement. Conclusions : The Stat Profile Critical Care Xpress multiprofile point-of-care analyzer provides rapid and accurate direct whole-blood measurement with acceptable performance compared to standard laboratory methods. The results obtained for electrolytes and substrates in whole blood were comparable to those for standard laboratory methods using arterial plasma or venous serum samples. Clin Chem Lab Med 2006;44:898–903.

Background : Determination of the length of sedimentation reaction in blood (LSRB) is frequently used in daily practice to assess disease intensity. Recently, a micro-sedimentation method was introduced (TEST 1™) that uses EDTA anti-coagulated blood samples. The aim of this study was to characterize this method by comparing it to a conventional Westergren method (Sedimatic 100). Furthermore, correlation between fibrinogen and the LSRB and the influence of M-proteins on the LSRB was investigated. Methods : Unselected paired samples were used for comparison between the TEST 1 and Sedimatic 100 methods (n=733); fibrinogen was measured in EDTA samples (n=765) using a turbidimetric method. Furthermore, LSRB was measured in 29 EDTA samples in paired serum tubes from patients in whom an M-protein was detected. Results : TEST 1 showed excellent correlation with the Sedimatic 100 method (y=1.00x; n=733; r=0.92, 95% CI 0.90–0.93; p<0.0001), and had no significant bias (0.15mm/h, 95% CI –0.48 to 0.75mm/h). Furthermore, TEST 1 LSRB showed satisfactory correlation with the fibrinogen content (y=3.13+0.06x; n=765; r=0.78, 95% CI 0.75–0.80; p<0.0001). In samples containing M-proteins, satisfactory correlation between the M-protein content and TEST 1 LSRB was found (y=0.69+0.22x; n=29; r=0.71, 95% CI 0.45–0.85; p<0.0001), while excellent correlation was found when only M-proteins of the IgM type were taken into account (y=–0.95+0.23x; n=9; r=0.93, 95% CI 0.71–0.99; p<0.0002). Conclusions : The results confirm previous reports that TEST 1 is a reliable method to measure the LSRB, and shows for the first time the quantitative relationship between TEST 1 LSRB and M-proteins, particularly those of the IgM type. Clin Chem Lab Med 2006;44:904–6.