Need for correct estimates of biological variation: the example of C-reactive protein.
Explore the source record for details and available documents.
C-Reactive Protein↗
Biomedical subjects
C Franzini
Publications and source records attributed to C Franzini.
Normalizing intermethod free triiodothyronine patient results: need for commutable materials.
The aim of this work was to check the suitability of control materials to normalize intermethod results for the measurement of free triiodothyronine in patient sera. In the main experiment, 108 patient sera and 11 commercially available control materials were assayed by a pair of methods. In a confirmatory experiment, two of the control materials and 142 patient sera were assayed with an alternative pair of methods. In the main experiment, the intermethod variability of 6/11 control materials differed significantly from that of patient sera (i. e. control materials were non-commutable). Recalculation of patient results using control materials as calibrators lowered the intermethod difference only if commutable materials were used. The confirmatory experiment demonstrated that the pattern of commutability changed if a different pair of methods was used. We conclude that in the case of free triiodothyronine the commutability of control materials should be tested if they are to be used to normalize patient results obtained by different methods.
Humans↗
Intermethod variability of sodium and potassium results: patients' sera and commercially available control sera.
Sodium and potassium were measured in sets of 102 to 107 patients sera, and in 31 commercially available control sera. The results from four routine analytical methods/systems (indirect potentiometry: two; direct potentiometry and enzymatic assay: one each) were compared with those from a flame photometry-based reference method. In the assay of patient sera, substantial agreement was observed in some comparisons, clinically relevant bias in others. The inter-assay changes observed for the control sera differed significantly from those shown by the patients sera (i.e. commercial control sera were non-commutable) in about 12% of the comparisons, as a whole. Recalculation of serum sample results with a single control serum as calibrator lowered or increased the bias originally present according to whether the serum itself was commutable or not. Moreover, the inter-method variability in the assay of commercial control sera was lower with commutable sera, higher with non-commutable sera. With the exception of liquid sera stabilized with ethylene glycol, there was no evident link between any specific characteristic of the commercial control sera (matrix and physical state) and their degree of commutability.
Animals↗
Accuracy of cholesterol measurements in Italian clinical laboratories. Joint project GISSI prevention--Italian Society of Clinical Biochemistry. SIBioC GISSI Prevenzione Group.
We report the results of an external quality assessment scheme for serum total cholesterol measurement involving about 100 Italian laboratories participating in an epidemiological study of post myocardial infarction. Two frozen human serum pools with Abell-Kendall assigned values are distributed quarterly at the laboratories (up to now seven events occurred); the obtained results are evaluated and discussed. In one exercise (# 5) duplicated measurements were repeated on three different days. Eighty-five to 98% of the laboratories obtained results within the total error limits (+/- 8.9%). But, while precision (calculated on the six replicates of exercise # 5) is good (90% of the laboratories obtained CV < 3%), inaccuracy problems are evident in every event. Indeed the mean bias from the reference method value ranged from 1.54 and 3.49% in the various events.
Analysis of Variance↗
[Controlled clinical study of doxophylline versus aminophylline in the treatment of acute cardiorespiratory insufficiency syndromes].
Twenty patients of both sexes, hospitalized because they were suffering from acute cardiorespiratory syndromes, have been studied in a clinical blind test on unbalanced groups of patients. This research aims to evaluate the therapeutic efficiency and intravenous tolerance of doxophylline. Patients were observed for 24 hours. Signs and symptoms were recorded on a semi-quantitative scale, and the clinical situation, haemogasanalysis, blood pressure, cardiac frequency, and other analytic controls were performed in order to verify the systemic tolerability. We can conclude, in agreement with the literature, that the group treated with doxophylline showed a better reduction in cardiac frequency, while maintaining the same effects on the respiratory apparatus.
Aminophylline↗
Creatinine measurement proficiency testing: assignment of matrix-adjusted ID GC-MS target values.
The results of an external quality-assessment experiment for serum creatinine measurement are described. Fifty-one laboratories performed quintuplicate analyses during three different analytical runs on six lyophilized sera and two frozen human serum pools. Isotope dilution gas chromatography-mass spectrometry (ID GC-MS) target values were assigned to all the materials. Intralaboratory within- and between-run imprecision results were very similar for all the materials tested (CV < or = 2.20% and < or = 4.70%, respectively). The overall imprecision obtained was high (CV 6.5-20.0%) because of increased interlaboratory-intermethod variability. A significant positive bias (+ 9.2-+43.7%) was found for all the materials at lower creatinine concentration. By using two human sera at different concentrations, we could calculate the constant and the proportional calibration bias displayed by each peer group. The majority of the lyophilized materials showed a behavior divergent from the frozen pools, indicating matrix-related problems. We propose a new algorithm for calculating matrix bias correction factor instrument-reagent specific for each material.
Algorithms↗
Current stage of standardization of measurements of specific polypeptides and proteins discussed in light of steps needed towards a comprehensive measurement system.
We present a standardization model for the measurement of specific polypeptides and proteins, which is based on an integrated development of all important elements of a reference measurement system. Generally, the model is in line with other current recommendations. However, it puts special emphasis on the definition of the analyte and on the role of reference methods for verification of the standardization process by measurement of patient specimens. Further, we discuss the needs for its implementation in the routine laboratory. In the light of this model, we investigate the current stage of standardization of routine methods for enzymes, peptide hormones, proteins, apolipoproteins, glycohaemoglobin, and tumour markers.
Apolipoproteins↗
Whole blood folate concentrations: comparison between Stratus Folate (DADE) and radioassay (DPC) methods.
The analytical performance of the Stratus Folate assay for intra-erythrocyte folate determination in normal subjects and in patients affected by folate-related diseases was compared with that of the radioassay (DPC) routinely employed by us. Folate concentrations were measured in freshly obtained EDTA whole blood from 100 subjects. Haemolysis was performed with the appropriate lysis reagent. In addition, to compare two different haemolysis procedures folate determination was carried out in 51 samples haemolysed according to the two procedures in parallel. Data were analyzed using Wilcoxon's test and standardized principal component analysis. Stratus Folate assay and radioassay performances were comparable in terms of analytical characteristics as well as in individual intraerythrocyte folate values across the range of whole blood concentrations examined in the survey. Significant differences were detected between the two different haemolysis procedures only for the radioassay. In conclusion, we observed no significant differences between the two folate determination methods despite their different analytical principles, which indicates the suitability of routine use of the automated non-isotopic Stratus Folate assay for clinical purposes. Moreover, with the latter assay the laboratory staff could choose the more convenient haemolysis procedure.
Automation↗
Brain capillary perfusion during sleep.
Brain capillary perfusion was evaluated in the different states of the wake-sleep cycle-quiet wakefulness (QW), quiet sleep (QS), and active sleep (AS)-in rats. The extent of the perfused capillary network was determined by intravascular distribution of a fluorescent marker. Evans blue (EB); it remained unchanged across the three behavioral conditions, QW, QS, and AS. The anatomical network was assessed by alkaline phosphatase (AP) endothelial staining, which is known to underestimate the number of existing capillaries. The resulting number of AP profiles were, therefore, significantly lower than the number of EB profiles, but the percentage of AP-stained capillaries that were perfused (96%) was also unchanged across the behavioral conditions. The results indicate that no capillary recruitment accompanies the wake-sleep cycle. Capillary surface area is a relevant factor in determining exchanges across the blood-brain barrier. In the absence of capillary recruitment (relative constancy of the surface area), the CBF changes during sleep should preferentially affect flow-limited with respect to diffusion-limited transport.
Animals↗
Inter-method differences in the measurement of some specific plasma proteins: commutability of control materials.
We compared the inter-method differences shown by control materials and by patients' sera for the measurement of some plasma proteins in the same pair of analytical systems. Sets of 100 to 110 samples of patients' sera and of 18-19 control materials, including the recently available CRM 470, were assayed with up to five automatic analytical systems, in two different experiments. About 5500 values were produced and assessed statistically. Materials (either patients' sera or control materials) were considered non-commutable (i.e. exhibiting significantly different inter-method behaviour) when their distance from the regression line in a stated pair of methods exceeded 3 standard deviations. According to this criterion, less than 1.5% of the patients' sera, and an even lower proportion of control materials were non-commutable. However, the inter-method behaviour of control materials was usually slightly different from that of patients' sera. Some systematic inter-method difference in the measurements on patients' sera may therefore exist, even though inter-method equivalence has been demonstrated with control materials.
Automation↗
Reference method for serum total cholesterol measurement: does substituting enzymatic step for Liebermann-Burchard reaction improve specificity?
Explore the source record for details and available documents.
Bacteria↗
Analytical specifications of reference methods compilation and critical discussion (from the members of the European EQA-Organizers Working Group B).
We present a compilation of published data for accuracy, precision, and measurement design for analytes that, currently, are of major interest for European reference laboratories. These data are compared with recent recommendations for performance of reference methods to be used within networks of European reference laboratories. In addition, we review the literature on reference methods and related topics.
Blood Glucose↗
Importance of pyridoxal-5'-phosphate addition to the assay medium for the measurement of catalytic concentrations of plasma aspartate and alanine aminotransferases in patients undergoing antineoplastic chemotherapy.
Using 98 plasma samples from cancer patients undergoing antineoplastic chemotherapy, we compared the activities of aspartate aminotransferase and alanine aminotransferase measured by two different methods, with and without the addition of pyridoxal-5'-phosphate to the assay medium. Pyridoxal-5'-phosphate caused an increase of 1 to 20 U/l in aspartate aminotransferase and alanine aminotransferase activity in 90 and 78 patient plasma samples, respectively. Increases of aspartate aminotransferase and alanine aminotransferase activity of more than 20 U/l were observed in 8 and 20 samples, respectively. In 8 cases, the increase in alanine aminotransferase activity was greater than 50 U/l, whereas a similar increase in aspartate aminotransferase activity was decreased in only 2 cases. The considerable pyridoxal-5'-phosphate activation in aminotransferase activity observed in the plasma of a significant number of patients suggests that the use of the method with pyridoxal-5'-phosphate is advisable for a correct measurement of the catalytic concentration of aminotransferases in the plasma of patients undergoing chemotherapy.
Alanine Transaminase↗
Continuous measurement of blood flow in the superior sagittal sinus of the lamb.
We assessed the validity of recording blood flow in the superior sagittal sinus (Qss) as a measure of cerebral blood flow (CBF). While anesthetized, 10 lambs were instrumented with a transit-time ultrasonic flow probe around the superior sagittal sinus to measure Qss, electrodes to assess sleep state, catheters to measure cerebral perfusion pressure (Pcp), and an occlusive cuff around the common brachiocephalic artery to vary blood pressure. After 72 h recovery, lambs were studied during spontaneous sleep-wake cycles to establish 1) the normal range of Qss and 2) the response rate of Qss to rapid alterations of Pcp. Subsequently, the lambs were reanesthetized, and the measurement of Qss was calibrated and validated. Qss was linearly related to the arterial inflow of 35% of the brain mass (y = 0.5 x + 1.6, r = 0.93, n = 4). Qss was greater in active sleep (154.1 +/- 45.7 ml.min-1 x 100 g-1, mean +/- SD, n = 5) than in quiet sleep (97.1 +/- 40.8 ml.min-1 x 100 g-1) and quiet wakefulness (107 +/- 44.3 ml.min-1 x 100 g-1, P < 0.05). Qss responded rapidly (within one beat) to spontaneous and to induced transient changes in Pcp. We conclude that recording blood flow in the superior sagittal sinus provides a simple, continuous, and quantitative measure of CBF from a defined area of the brain and is appropriate for studying transient changes in the cerebral circulation.
Animals↗
Relevance of analytical and biological variations to quality and interpretation of test results: examples of application to haematology.
In the frame of a comprehensive quality system, the level of quality to be attained (analytical goals or quality specifications) need to be defined. Among the several approaches used for such a definition, that based on the (intra-individual) biological variation seems to be scientifically sound, and the most universally applicable. Data on biological variation are easily generated by applying specific experimental protocols. Once the biological variation is known, it can be combined to the analytical variation for the calculation of the critical difference. This is the difference between two repeated measurements in the same patient, due to the effect of both analytical and biological variation: when this difference is exceeded, a significant change in the patient's condition can be assumed. Some examples of calculation of the analytical goals and of the critical differences are shown, based on some quantities usually measured in the haematological laboratory.
Analysis of Variance↗
Analytical quality specifications for reference methods and operating specifications for networks of reference laboratories. discussion paper from the members of the external quality assessment (EQA) Working Group B1) on target values in EQAS.
The aim of the Working Group was to describe guidelines for the establishment of networks of reference laboratories. The need for such networks to achieve an accuracy-based uniform measurement system with traceability of results of analytical systems/test-kits to the true value is outlined. Criteria for analytical quality specifications, which are related to the ultimate purpose of the reference method and thereby to the objectives of the networks, are emphasized. The group recommends the use of two models: one based on specifications for routine methods, which are dictated by the biological variations of the respective analytes, the second respecting the analytical state-of-the-art of reference methodology. Further, the group presents operating specifications for networks that guarantee the continuous performance of reference method measurements whilst maintaining a uniform and stable level of quality.
Chemistry, Clinical↗
Brain blood flow and extracerebral carotid circulation during sleep in rat.
Cerebral blood flow (CBF) and blood flow (BF) in extracerebral head structures were measured during the sleep-wake cycle in rats using radioactive microspheres. While no statistically significant changes occurred in the transition from Waking to quiet sleep (also referred to as synchronized or non-REM Sleep), CBF increased significantly in active sleep (AS, also referred to as desynchronized or REM Sleep) in all structures considered, with the sole exception of the cerebellum. In extracerebral head structures, no significant state-dependent BF changes were found. Factor Analysis however extracted a common factor accounting for BF variability in the external carotid circulation. This factor was uncorrelated with CBF changes in AS, suggesting independent regulation of the two vascular beds in this sleep state.
Animals↗
Spinal cord blood flow changes during the sleep-wake cycle in rat.
Regional spinal cord blood flow was measured in rats during the sleep-wake cycle with the use of radioactive microspheres. Spinal cord blood flow decreases from wakefulness to quiet (synchronized) sleep while increasing in active (desynchronized) sleep. Blood-flow changes depend on changes in vascular resistance whose mechanisms have yet to be elucidated. Blood-gas tension or mean arterial pressure, however, do not play a relevant causal role.
Animals↗