Factors contributing to intra-individual variation of serum constituents: Physiological day-to-day variation in concentrations of 10 specific proteins in sera of healthy subjects.

1976 ◽  
Vol 22 (10) ◽  
pp. 1635-1638 ◽  
Author(s):  
B E Statland ◽  
P Winkel ◽  
L M Killingsworth

Abstract Using an automated immunoprecipitin method, we assayed human sera for 10 proteins: haptoglobin, orosomucoid, transferrin, alpha1 antitrypsin, alpha2-macroglobulin, IgG, IGa, IgM, complement C3, and complement C4. Blood from 14 healthy subjects (25-40y) was sampled on six separate days. From each venipuncture serum was divided into four eliquots; two were assayed on the day of venipuncture and two were frozen and kept until the end of the study, when all of the frozen samples were analyzed in one batch. With this experimental design, batch-to-batch analytical variation could be estimated, and we avoided confounding it with the biological variation. Data analysis was based on the analysis of variance technique. The average physiological intra-individual coefficient of variation ranged from 2.5% for transferrin to 11.1% for orosomucoid. THe interindividual variation ranged from 9.5% for transferrin to 70.5% for haptoglobin and the ratio between intra-individual variation and interindividual variation ranged from 0.66 for IgM to 0.26 for orosomucoid and transferrin.

Author(s):  
Fatma Ucar ◽  
Gonul Erden ◽  
Seyda Ozdemir ◽  
Nurgul Ozcan ◽  
Erdem Bulut ◽  
...  

AbstractBackground:Most of the factors causing preanalytical and analytical variation in ammonia measurement have been identified. Biological variation data for ammonia is still lacking. We therefore estimated the components of biological variation (within-subject=CVMethods:Blood samples from 20 healthy subjects were collected in K2EDTA tubes daily over a period of 4 consecutive days from each subject. Each plasma sample was split into two aliquots; one was immediately analyzed as the samples were collected and the other was stored –80 °C until testing at the end of the collection period and analyzed at once in one analytical run. All samples were analyzed in duplicate. Estimations were calculated according to Fraser and Harris methods.Results:CVConclusions:The present study for the first time described the components of biological variation for ammonia in healthy individuals. These data regarding biological variation of ammonia could be useful for a better evaluation of ammonia test results in clinical interpretation and for determining quality specifications based on biological variation.


1973 ◽  
Vol 19 (12) ◽  
pp. 1374-1379 ◽  
Author(s):  
Bernard E Statland ◽  
Per Winkel ◽  
Henning Bokelund

Abstract We evaluated the within-day variation of serum constituents in a group of 11 healthy young men. Twenty-two constituents were assayed at the same time, 19 of them on the " AutoChemist" multi-channel analyzer. The statistical model of analysis-of-variance was used to separate certain factors—subject, time of day, and subject-time interaction— from the analytical variation. The estimate of analytical variation was based on data for duplicate samples of blood which were taken from all subjects at 0800 h, 1100 h, and 1400 h. The following serum constituents varied significantly (P <0.05) as a function of time of day: sodium, potassium, chloride, urea, iron, bilirubin, total lipids, and acid phosphatase.


Author(s):  
Carmen Ricós ◽  
Pilar Fernández-Calle ◽  
Elisabet Gonzalez-Lao ◽  
Margarida Simón ◽  
Jorge Díaz-Garzón ◽  
...  

AbstractObjectivesNumerous biological variation (BV) studies have been performed over the years, but the quality of these studies vary. The objectives of this study were to perform a systematic review and critical appraisal of BV studies on glycosylated albumin and to deliver updated BV estimates for glucose and HbA1c, including recently published high-quality studies such as the European Biological Variation study (EuBIVAS).MethodsSystematic literature searches were performed to identify BV studies. Nine publications not included in a previous review were identified; four for glycosylated albumin, three for glucose, and three for HbA1c. Relevant studies were appraised by the Biological Variation Data Critical Appraisal Checklist (BIVAC). Global BV estimates were derived by meta-analysis of BIVAC-compliant studies in healthy subjects with similar study design.ResultsOne study received BIVAC grade A, 2B, and 6C. In most cases, the C-grade was associated with deficiencies in statistical analysis. BV estimates for glycosylated albumin were: CVI=1.4% (1.2–2.1) and CVG=5.7% (4.7–10.6), whereas estimates for HbA1c, CVI=1.2% (0.3–2.5), CVG=5.4% (3.3–7.3), and glucose, CVI=5.0% (4.1–12.0), CVG=8.1% (2.7–10.8) did not differ from previously published global estimates.ConclusionsThe critical appraisal and rating of BV studies according to their methodological quality, followed by a meta-analysis, generate robust, and reliable BV estimates. This study delivers updated and evidence-based BV estimates for glycosylated albumin, glucose and HbA1c.


1974 ◽  
Vol 20 (12) ◽  
pp. 1507-1512 ◽  
Author(s):  
Henning Bokelund ◽  
Per Winkel ◽  
Bernard E Statland

Abstract In study of intra-individual variation of serum constituents, we used analysis of variance to separate biological from analytical variation, the latter being estimated from results for duplicate specimens. However, the replication error term in such a model may grossly overestimate instrumental variability, especially when a significant pre-instrumental error component is present. To separate pre-instrumental and instrumental error, we used the following experimental design: Duplicate serum specimens were obtained from 88 healthy men, the blood being collected at one venipuncture and immediately divided into two portions. The duplicates were randomized and analyzed on one occasion with the "AutoChemist Multi-Channel Analyzer," and pre-instrumental variation was estimated from the results. Instrumental variation was estimated from results for three independent populations with widely different mean analyte concentrations; these samples were analyzed at the same time as the samples just mentioned. Of the 20 serum constituents assayed, sodium, potassium, iron, total lipids, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and total bilirubin showed significant pre-instrumental error components, as evidenced from significant χ2-tests comparing analytical and "duplicate sample" variation. For total serum protein, albumin, total lipids, cholesterol, and alkaline phosphatase, we found a significant difference (by paired t-test) between values for the first and second specimen.


1982 ◽  
Vol 100 (1) ◽  
pp. 154-160 ◽  
Author(s):  
D. Berg ◽  
F. Thaler ◽  
E. Kuss

Abstract. A heterologous immunoassay for 2-hydroxyoestrogens1 has been established in which antibodies raised against 2-hydroxyoestradiol-17-succinyl-BSA serve as binding protein and 2-hydroxyoestrone-17-cmo-[125I]iodohistamine as radioligand. Lipophilic serum components competing for binding sites in this system were defined as 'total 2-hydroxyoestrogens'. The underlying assumption of specificity was supported by the pattern of cross-reactivity evaluated with structural related steroids and o-diphenols and by the fact, that an additional chromatography of the serum extracts preceding the competing reaction had little if any effect. Sensitivity: 2.8 ± 1 pg/tube; accuracy: Y = 0.91x + 2.2; r = 0.989; precision: 5.8% intra-assay; 6.5% inter-assay. The following concentrations ( ± standard deviation) were found in the sera of healthy subjects. Young men: 29 ± 5 pg/ml (n = 11); women follicular phase: 32 ± 8 pg/ml (n = 25); luteal phase: 53 ± 13 pg/ml (n = 23); postmenopausal women: 13 ± 4 pg/ml (n = 10); pregnant women 11th–20th week: 70 ± 16 mg/ml (n = 64); 36th–40th week: 240 ± 23 pg/ml (n = 40); newborn cord blood: 604 ± 43 pg/ml (n = 48).


1987 ◽  
Vol 33 (7) ◽  
pp. 1133-1136 ◽  
Author(s):  
W G Hölzel

Abstract The average biological intra-individual CV in 20 patients with chronic liver diseases (CLD), estimated for 14 analytes during a stationary phase, significantly exceeded that for a normal group in the cases of Na+, K+, Cl-, total protein, albumin, cholinesterase, hemoglobin, and alpha-amylase; it did not differ significantly from the normal group for cholesterol, alkaline phosphatase, aspartate aminotransferase, and alanine aminopeptidase; and it was significantly lower than in the normal group for alanine aminotransferase and gamma-glutamyltransferase. There were no significant sex-related differences in mean intra-individual variation in CLD patients. Individual values were gaussian-distributed for all analytes, including enzymes. The estimated biological component of intra-individual variation and the analytical variation as determined for each laboratory can be used to derive decision-making criteria in monitoring CLD.


1977 ◽  
Vol 23 (3) ◽  
pp. 511-514 ◽  
Author(s):  
W C Butts ◽  
G E James ◽  
M Keuhneman

Abstract A recent study [Clin. Chem. 22, 1635 (1976)] reported intra-individual variation in 10 serum proteins to be much smaller than interindividual variation. We report results of a similar study involving about 700 apparently healthy adults in whom we estimated the relative magnitude of the intra- and interindividual variation in serum IgA, IgG, IgM and complement component C3. Specimens were collected from each subject weekly for as long as 10 weeks (average, four weeks). The four serum proteins were quantitated by radial immunodiffusion by the maximal-diffusion technique. Traditional 95% reference intervals were computed relative to WHO reference preparations for the immunoglobulins. For C3, the reference interval was computed relative to a commercial reference preparation. We, too, found the ratios of intra-individual to interindividual variation for adults to be so small that the traditional reference intervals do not have the assumed diagnostic sensitivities. Furthermore, these ratios did not change after dividing the study population into subgroups according to sex and age; evidently such subgrouping do not improve the diagnostic sensitivity. The relatively small intra-individual variations were also observed at the extremes of protein concentration ranges.


BMC Genomics ◽  
2007 ◽  
Vol 8 (1) ◽  
pp. 93 ◽  
Author(s):  
Guojie Zhang ◽  
Hongsheng Wang ◽  
Junjie Shi ◽  
Xiaoling Wang ◽  
Hongkun Zheng ◽  
...  

Author(s):  
Judith M. Hilderink ◽  
Lieke J.J. Klinkenberg ◽  
Kristin M. Aakre ◽  
Norbert C.J. de Wit ◽  
Yvonne M.C. Henskens ◽  
...  

AbstractBackground:Middle- and long-term biological variation data for hematological parameters have been reported in the literature. Within-day 24-h variability profiles for hematological parameters are currently lacking. However, comprehensive hour-to-hour variability data are critical to detect diurnal cyclical rhythms, and to take into account the ‘time of sample collection’ as a possible determinant of natural fluctuation. In this study, we assessed 24-h variation profiles for 20 hematological parameters.Methods:Blood samples were collected under standardized conditions from 24 subjects every hour for 24 h. At each measurement, 20 hematological parameters were determined in duplicate. Analytical variation (CVResults:All parameters showed higher CVConclusions:We present complete 24-h variability profiles for 20 hematological parameters. Hour-to-hour reference changes values may help to better discriminate between random fluctuations and true changes in parameters with rhythmic diurnal oscillations.


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