To the Editor:
For adequate longitudinal investigation of individual patients, clinicians rely on long-term stability of laboratory data. This requirement is also essential to maximize the benefits and outcome of clinical trials and epidemiologic studies extended over several years. The long-term stability of laboratory measurements has scarcely been documented, however, and quality criteria are lacking. We selected sodium measurement in serum/plasma to serve as a benchmark for achievable stability, because this analyte receives the most attention by the in vitro diagnostics industry in terms of restricting lot-to-lot variation. Moreover, we believe that with these data as a benchmark, industry can establish specifications for the realistic stability of assays used for the measurement of other analytes.
For this purpose, we investigated the sodium results from Ghent University Hospital (in serum and in lithium heparin–treated plasma) and Brussels University Hospital (in lithium heparin–treated plasma) covering the period from December 2001 to August 2010 and from January 1997 to October 2010, respectively. We calculated the daily 10th, 50th, and 90th percentiles, with exclusion of the measurements made on weekends and holidays. …
Both high resolution sector field ICP-MS (ICP-SFMS) and quadrupole ICP-MS (ICP-QMS), with and without the collision cell technology, were used to investigate interferences observed in the analysis of cadmium in whole blood. Interference tests were performed, in which blood samples were spiked with K, Na2EDTA and Mo. Significant interferences were observed on the 111Cd isotope, especially in K-spiked samples. Interferences were more pronounced on the ICP-SFMS than on the ICP-QMS. Accurate Cd analysis in blood samples can be performed on both instruments using the 114Cd isotope after mathematical corrections for 114Sn and 98Mo16O.
We evaluated the imprecision and bias of three instruments for the determination of blood gases, pH and ionized calcium (Ca(2+)) in human arterial blood samples, in comparison with the performance of an established methodology.The ABL 735, Omni S and Rapidpoint 405 blood gas analyzers were evaluated and compared to the ABL 620 analyzer. Imprecision was determined according to the NCCLS EP10-A2 evaluation protocol. The NCCLS EP9-A2 evaluation protocol was used to determine bias relative to the ABL 620 system. Experimental data were compared against preset quality specifications.The three new instruments showed excellent imprecision for the measurement of pH, but only the ABL 620 met the preset imprecision goals for all analytes tested. All new instruments showed good correlation with the comparative instrument. The slope of the regression equation was significantly different from 1.0 in six out of the 12 comparisons, indicating systematic differences between the instruments. Nevertheless, the predicted bias values relative to the comparative instrument did not exceed the preset quality specifications for two out of the three new instruments.Preliminary evaluation using the NCCLS evaluation protocols EP10-A2 and EP9-A2, may provide valuable information on performance characteristics of blood gas analyzers.
Elevated circulating total homocysteine is an independent vascular risk factor. Enzymatic homocysteine measurements represent an alternative to HPLC- or immunochemistry-based assays, suitable for automation. Here, we report on analytical performance of a commercial cystathionine beta-synthase-based assay, for use on Vitros automated analyzers.Linear range, limit of detection and analytical sensitivity were inferred from duplicate measurements of homocystine standard solutions (1-65 micromol/L). Imprecision was assessed using commercial controls according to NCCLS EP5-A2 and accuracy using NIST-SRM1955 reference material. Agreement with a clinically validated HPLC method was examined on 207 patient samples.The enzymatic assay was linear from 1 to 90 micromol/L homocysteine. Total (within-day) imprecision ranged from 4.5 (3.9)% to 2.8 (1.6)% at homocysteine 9.7-43.2 micromol/L. Accuracy was acceptable at 8.9 and 17.7 micromol/L homocysteine, with +6.4% and -1.2% bias, respectively, but showed substantial negative bias (-20.1%) at 4.0 micromol/L. High triglycerides (19.8 micromol/L) negatively interfered. The enzymatic method was slightly less sensitive than the HPLC method (limit of detection 0.7 and 0.2 micromol/L, respectively) but correlated well with the latter (r2=0.9997, slope=1.04, intercept=-0.66 micromol/L) and was more precise (p<0.05).The Vitros homocysteine assay met the CLIA Desirable Analytical Quality Specifications at homocysteine > or = 9 micromol/L. Its analytical performance and suitability for automation make the Vitros assay an analytically acceptable alternative to HPLC-based methods.
Diabetes registries have documented that the lifetime risk of diabetes amounts to at least 10% in the western world. Moreover the prevalence of type 2 diabetes is increasing worldwide especially in developing countries. Furthermore there is a secular trend toward earlier clinical manifestation of both type 1 and type 2 diabetes. In the absence of a permanent cure for primary diabetes the present estimated number of at least 150 million diabetic patients worldwide is expected to double within the next 20 years. Consequently a sharp increase in the global burden of chronic diabetes complications is to be feared in the coming decades. Therefore it is absolutely mandatory to intensify research efforts aiming at identifying the etiological factors involved and designing effective strategies for prediction and prevention of the disease and its devastating complications. Diabetes registries constitute instruments of choice to conduct such studies because they are able to collect standardised clinical, demographic and biological information from sufficiently large representative groups of patients and risk groups such as first degree relatives. Since 1989, the Belgian Diabetes Registry is studying all types of diabetes presenting before age 40 in Belgium and provides a paradigm of how diabetes registries may also contribute to the advancement of knowledge on disease heterogeneity, etiology, prediction and prevention.
Circulating myoglobin is recognized as an early and sensitive marker of acute coronary diseases. Long turnaround time of myoglobin assays jeopardize their clinical utility. We evaluated the analytical performance of the Stratus® CS fluorometric enzyme immunoassay based on dendrimer technology, and claimed to achieve a fast and reliable determination of plasma myoglobin concentrations. Precision complied with the recommended analytical performance criteria. Method comparison and recovery experiments indicated, that despite good between-method correlations, the Stratus® CS method overestimated myoglobin concentrations in comparison with values obtained on Cobas® Integra 400 and BN™A. However, since the manufacturers’ cut-off for elevated plasma myoglobin levels was higher for Stratus® CS than for other techniques, few discrepant results were observed between methods. Elevated levels of hemoglobin, triglycerides and rheumatoid factors did not interfere in the Stratus® CS method but hyperbilirubinemia caused a positive difference.Circulerend myoglobine wordt beschouwd als een vroege en gevoelige merker voor acute coronaire aandoeningen. De lange analysetijd beknot echter de klinische bruikbaarheid van myoglobine-assays. We evalueerden de analytische performantie van de op dendrimeertechnologie gebaseerde Stratus® CS fluorometrische enzym-immunoassay, en bevonden de assay als een snelle en betrouwbare bepalingsmethode voor myoglobineconcentraties in plasma. De precisie voldeed aan de aanbevolen analytische performantiecriteria. Methodenvergelijking en recovery-experimenten toonden, ondanks de bevredigende correlaties tussen de verschillende methodes, een overschatting aan van de myoglobineconcentraties bepaald met Stratus® CS, in vergelijking met deze bepaald met Cobas® Integra 400 en BN™A. Daar de door de fabrikant vermelde cut-off voor verhoogde myoglobineconcentraties in plasma hoger was voor Stratus® CS dan voor de andere methoden, werden slechts weinig discrepante resultaten tussen de verschillende methoden teruggevonden. Verhoogde concentraties aan hemoglobine, triglyceriden en reumatoïde factoren, interfereerden niet met de Stratus® CS-methode, doch hyperbilirubinemie veroorzaakte een positief verschil.
Multiple myeloma is a B-cell neoplasm characterized by the monoclonal proliferation of plasma cells in the bone marrow, the development of osteolytic lesions, and the induction of angiogenesis. These different processes require three-dimensional interactions, with both humoral and cellular contacts. The 5TMM models are suitable to study these interactions. These are murine models that originate from spontaneously developed myeloma in elderly mice. They are propagated by in vivo transfer of the myeloma cells into young syngeneic mice. We report methods involving the maintenance of the 5T2MM model and the quantification of tumor burden (by determining serum paraprotein concentration and plasmacytosis), assessment of bone lesions, and quantification of angiogenesis. The combination of these different techniques in these models not only helps in unraveling basic biological processes but also in the testing of potentially new therapeutic targets.
