Factors Contributing to Intra-Individual Variation of Serum Constituents: 1. Within-Day Variation of Serum Constituents in Healthy Subjects

1973 ◽  
Vol 19 (12) ◽  
pp. 1374-1379 ◽  
Author(s):  
Bernard E Statland ◽  
Per Winkel ◽  
Henning Bokelund
Keyword(s):  
Acid Phosphatase ◽  
Statistical Model ◽  
Individual Variation ◽  
Healthy Subjects ◽  
Time Of Day ◽  
Total Lipids ◽  
Sodium Potassium ◽  
Time Interaction ◽  
Channel Analyzer ◽  
Analytical Variation

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.

Factors Contributing to Intra-Individual Variation of Serum Constituents: 3. Use of Randomized Duplicate Serum Specimens to Evaluate Sources of Analytical Error

1974 ◽  
Vol 20 (12) ◽  
pp. 1507-1512 ◽  
Author(s):  
Henning Bokelund ◽  
Per Winkel ◽  
Bernard E Statland
Keyword(s):  
Individual Variation ◽  
Error Component ◽  
Instrumental Error ◽  
Total Serum Protein ◽  
Total Serum ◽  
Total Lipids ◽  
Significant Difference ◽  
Channel Analyzer ◽  
Analytical Variation ◽  
Duplicate Sample

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.

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
Keyword(s):  
Data Analysis ◽  
Individual Variation ◽  
Healthy Subjects ◽  
Interindividual Variation ◽  
Complement C3 ◽  
Variation Data ◽  
Human Sera ◽  
Specific Proteins ◽  
Alpha1 Antitrypsin ◽  
Analytical Variation

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.

Intra-individual variation of analytes in serum from patients with chronic liver diseases.

1987 ◽  
Vol 33 (7) ◽  
pp. 1133-1136 ◽  
Author(s):  
W G Hölzel
Keyword(s):  
Individual Variation ◽  
Liver Diseases ◽  
Normal Group ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Individual Values ◽  
Gamma Glutamyltransferase ◽  
Alanine Aminopeptidase ◽  
Biological Component ◽  
Analytical Variation

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.

Factors Contributing to Intra-Individual Variation of Serum Constituents: 5. Short-Term Day-to-Day and Within-Hour Variation of Serum Constituents in Healthy Subjects

1974 ◽  
Vol 20 (12) ◽  
pp. 1520-1527 ◽  
Author(s):  
Per Winkel ◽  
Bernard E Statland ◽  
Henning Bokelund
Keyword(s):  
Total Lipids ◽  
Short Term ◽  
Serum Samples ◽  
Interaction Terms ◽  
Anova Model ◽  
First Case ◽  
Main Effect ◽  
Relationship Of ◽  
The Relationship ◽  
Analytical Variation

Abstract We evaluated the variations in some serum constituents in a group of healthy young men for two selected time intervals: short-term day-to-day changes and within-hour changes. In the first case, we used a two-way ANOVA model to compute the main-day effect and the subject-day interaction terms, which were combined to yield the total day-to-day variation. A main-day effect was seen to be statistically significant only for acid phosphatase, while all of the 18 serum constituents except for sodium, calcium, and albumin demonstrated a statistically significant subject-day interaction. For the within-hour biologic variation, a three-way ANOVA model was used to analyze results of duplicate serum samples drawn at 1100 h and 1130 h on two different days. Although a significant main effect of hour was found only for total lipids and alkaline phosphatase, pooling the main effect of hour, subject-hour interaction, and subject-day-hour interaction terms resulted in a chemically significant variation for potassium, total protein, albumin, iron, total lipids, cholesterol, and bilirubin. The relationship of these biological fluctuations is compared to the expected analytical variation in all cases.

Water Balance and Kidney Function in Four Species of Rattus From Ecologically Diverse Environments.

1976 ◽  
Vol 24 (1) ◽  
pp. 7 ◽  
Author(s):  
PR Baverstock
Keyword(s):  
Drinking Water ◽  
Water Balance ◽  
Osmotic Pressure ◽  
Individual Variation ◽  
Water Deprivation ◽  
High Metabolic Rate ◽  
Sodium Potassium ◽  
Rattus Fuscipes ◽  
Microhabitat Preferences ◽  
Urine Concentrating Ability

While Rattus fuscipes survived only 4 days of water deprivation at 21�C, R. norvegicus, R. villosissimus and R. lutreolus survived 13-16 days. There was considerable inter-individual variation in the response of water-deprived R. villosissimus. Analysis of osmotic pressure, urea, sodium, potassium and chloride of both plasma and urine of rats with and without drinking water revealed that: (1) the abilities of R. norvegicus and R. villosissimus to tolerate water deprivation were due in large part to their abilities to produce highly concentrated urine; (2) R. lutreolus tolerated long periods of water deprivation not by urine-concentrating ability but by partly abandoning homeostasis and tolerating elevated levels of plasma solutes; (3) water-deprived R. fuscipes excreted large volumes of concentrated urine, possibly because their relatively high metabolic rate necessitated the excretion of excess metabolites. In all of the rats, urea constituted an unusually low proportion of the total osmotic pressure. The water-balance response of water-deprived rats is at variance with both their macrogeographical distribution and microhabitat preferences.

Factors Contributing to Intra-Individual Variation of Serum Constituents: 4. Effects of Posture and Tourniquet Application on Variation of Serum Constituents in Healthy Subjects

1974 ◽  
Vol 20 (12) ◽  
pp. 1513-1519 ◽  
Author(s):  
Bernard E Statland ◽  
Henning Bokelund ◽  
Per Winkel
Keyword(s):  
Total Lipid ◽  
Serum Potassium ◽  
Individual Variation ◽  
Total Protein ◽  
Aspartate Aminotransferase ◽  
Tourniquet Time ◽  
Phosphate Ion ◽  
Condition C ◽  
Channel Analyzer ◽  
Condition B

Abstract We studied the effects on 18 serum constituents of posture and prolonged tourniquet application. The subjects were 11 healthy men, ages 20-25 years. The assays were performed on the AutoChemist Multi-Channel Analyzer (AutoChem Instrument AB, Lidingö, Sweden). To compensate for the within-hour variation in these constituents, we drew blood samples at 1100 h and 1130 h on several days. The 1100-h sample was taken after the subjects had been sitting erect for 60 min. The 1130-h sample followed different posture regimens: Control day: sitting for 15 min; experimental days: after (a) being supine for 30 min, (b) standing for 30 min, and (c) sitting erect for 30 min. The 1130-h/ 1100-h ratios for the three experimental days were compared with those for the control day. Significant differences (P <.05) were found for serum potassium, calcium, total protein, albumin, aspartate aminotransferase, and acid phosphatase under condition a; for phosphate ion, total protein, total lipid, cholesterol, and alkaline phosphatase under condition b; and for aspartate aminotransferase under condition c. The effect of a 3-minute tourniquet application was similarly studied. The ratio of the "prolonged tourniquet application day" differed significantly from the control day with regard to serum potassium, total protein, iron, total lipid, cholesterol, aspartate aminotransferase, and bilirubin. Significance of posture and tourniquet time in blood-sampling and their effect on total intra-individual variation are discussed.

scholarly journals Clinical Significance of Immunoassays for Type-5 Tartrate-resistant Acid Phosphatase

1999 ◽  
Vol 45 (12) ◽  
pp. 2150-2157 ◽  
Author(s):  
Yuri R Nakasato ◽  
Anthony J Janckila ◽  
Jussi M Halleen ◽  
H Kalervo Vaananen ◽  
Stephanie P Walton ◽  
...  
Keyword(s):  
Acid Phosphatase ◽  
Rheumatic Disease ◽  
Healthy Subjects ◽  
Specific Activity ◽  
Biological Significance ◽  
Tartrate Resistant Acid Phosphatase ◽  
Endstage Renal Disease ◽  
Trap Activity ◽  
Specificity And Sensitivity ◽  
The Mean

Abstract Background: Tartrate-resistant acid phosphatase (TRAP; EC 3.1.3.2) is a product of osteoclasts and a biochemical marker of bone resorption rate. However, erythrocytes and platelets contribute to total TRAP activity in serum, reducing the specificity of direct biochemical assays in serum. Osteoclast TRAP is also known as type-5 TRAP and is antigenically unique. Immunoassays are sought to improve the specificity and sensitivity of TRAP as a bone marker. Methods: We developed two colorimetric microplate assays for type-5 TRAP: an enzyme capture immunoassay to measure antibody-bound enzymatic activity, and a two-site immunoassay to measure bound enzyme protein. Both use the same monoclonal antibody (14G6) to capture type-5 TRAP, which permits determination of specific activity of serum TRAP in health and disease. Results: Both TRAP assays were linear from one-tenth to fivefold the mean value in 18 healthy subjects. In these subjects, the mean (SD) TRAP activity was 3.2 (0.54) U/L for the enzyme capture assay and 37 (13) μg/L for the two-site assay. Mean TRAP activity was not significantly increased in 64 patients with endstage renal disease requiring hemodialysis (HD) or 99 unselected patients with rheumatic diseases. By contrast, TRAP protein was increased in both the HD and rheumatic disease groups. The specific activity of TRAP in the 17 of 64 HD sera that had increased TRAP activity (0.088 U/μg) was similar to that in healthy subjects (0.091 U/μg). By contrast, the specific activity of TRAP in the 31 of 99 rheumatic sera with increased TRAP protein (0.035 U/μg) was significantly decreased. Conclusions: Wide sample distributions for TRAP activity in HD patients and TRAP protein in rheumatic disease patients suggest the presence of subpopulations of HD patients with increased TRAP activity and of rheumatic patients with increased TRAP protein. Each assay for TRAP activity and protein may have its own biological significance and clinical applications in specific groups of patients.

Factors Contributing to Intra-Individual Variation of Serum Constituents: 2. Effects of Exercise and Diet on Variation of Serum Constituents in Healthy Subjects

1973 ◽  
Vol 19 (12) ◽  
pp. 1380-1383 ◽  
Author(s):  
Bernard E Statland ◽  
Per Winkel ◽  
Henning Bokelund
Keyword(s):  
Uric Acid ◽  
Healthy Subjects ◽  
Sodium Phosphate ◽  
Statistical Significance ◽  
Potassium Phosphate ◽  
Strenuous Exercise ◽  
Fasting State ◽  
Total Lipids ◽  
Physiological Factors ◽  
Methodological Considerations

Abstract A previous report of within-day variation of serum constituents was based on values in healthy subjects who did not undergo strenuous exercise and who were in a fasting state. In this study we consider the effects of exercise and of a noon meal on the same serum constituents. The statistical significance (t-test) was computed on the basis of the ratios of values (after/before) on the day of exercise vs. the ratios on the nonexercise day, or, for the effect of meal, the ratios of values (after/before the noon meal) on the eating day vs. the ratios of values taken at the same hour on the fasting day. Significant effects seen after exercise (P <.05) included: potassium, phosphate, creatinine, total protein, albumin, uric acid, and alanine aminotransferase. After the noon meal, significant (P <.05) changes were seen for: sodium, phosphate, uric acid, iron, total lipids, alkaline phosphatase (phenyl phosphate substrate), and lactate dehydrogenase. The effects of eating on serum constituents are separated into (a) physiological factors and (b) methodological considerations.

Platelet Microrna-mRNA Co-Expression Profiles Correlate with Platelet Reactivity

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2016-2016
Author(s):  
Srikanth Nagalla ◽  
Chad Shaw ◽  
Xianguo Kong ◽  
Lin Ma ◽  
Altaf A. Kondkar ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Protein Expression ◽  
Reporter Gene ◽  
Microarray Analysis ◽  
Individual Variation ◽  
Healthy Subjects ◽  
Platelet Reactivity ◽  
Human Platelets ◽  
Differentially Expressed ◽  
Cell Physiology

Abstract Abstract 2016 Background: There is extreme inter-individual variation in platelet reactivity, which likely impacts the variation in both risk and clinical outcome of ischemic vascular disease since platelet hyperreactivity has prospectively been shown to be a risk for recurrent coronary syndromes. Although heritability strongly influences the inter-individual variation in platelet reactivity, there is a lack of understanding of the molecular and genetic mechanisms responsible for this variability. To understand some of these mechanisms, we have previously performed mRNA microarray analysis on platelets of subjects with differing levels of platelet reactivity. We showed a differentially expressed (DE) transcript (VAMP8) was associated with platelet reactivity. Intriguingly, we identified a possible role for microRNA (miRNA)-96 in the regulation of VAMP8 mRNA and protein expression. MiRNAs regulate numerous aspects of normal cell physiology and cause disease by altering protein expression, and recent data demonstrate a role for miRNAs in both normal and diseased human megakaryocytopoiesis. Although others and we have observed miRNAs in platelets, their biology is largely unexplored. Aims: To test whether platelet miRNA levels were associated with platelet reactivity in 19 healthy subjects. Because we had previously obtained platelet mRNA profile data on these 19 subjects, we also had a unique opportunity to test for relationships between differentially expressed miRNAs and target DE mRNAs. Methods: MiRNA microarray analysis was performed on leukocyte depleted platelets from 19 healthy subjects with marked variability in platelet responsiveness. Bioinformatics approaches were used analyze the miRNA data in platelets. Subsequently transfection experiments in cell lines to assess miRNA knockdown of target gene products and reporter gene assays were used for functional assessment of miRNA binding to 3’UTRs of the target genes. Results: We found that human platelets express 284 miRNAs, some at very high levels. Unsupervised hierarchical clustering of miRNA profiles resulted in two groups of subjects that appeared to cluster by platelet aggregation phenotypes. Seventy-four miRNAs were differentially expressed between subjects grouped according to platelet aggregation to epinephrine, a subset of which predicted the platelet reactivity response. We profiled miRNAs from HEL and Meg-01 cells and found a strong correlation between normal human platelets and both HEL cells and Meg-01 cells. Using whole-genome mRNA expression data on these same 19 subjects, we computationally generated a high-priority list of miRNA-mRNA pairs where the differentially expressed platelet miRNAs had binding sites in 3’UTRs of differentially expressed mRNAs, and the levels were negatively correlated. From this list, three miRNA-mRNA pairs (miR-200b:PRKAR2B, miR-495:KLHL5 and miR-107:CLOCK) were selected, and all three miRNAs knocked down the protein expression of the target mRNA. Co-transfection experiments using reporter gene constructs engineered to contain the candidate mRNA 3’UTR and corresponding miRNA demonstrated that the miRNA of interest directly targeted the 3’UTR of the candidate mRNA. Conclusions: Results from this study demonstrated (1) platelet miRNAs are able to repress expression of platelet proteins; (2) platelet miRNA profiles are associated with and may predict platelet reactivity and (3) bioinformatic approaches can successfully identify functional miRNAs in platelets. Our findings suggest that selected platelet miRNAs may have potential as biomarkers for vascular thrombosis. It will be important to consider the repertoire and levels of miRNAs when attempting to elucidate the molecular mechanisms responsible for inter-individual variation in platelet reactivity. Disclosures: No relevant conflicts of interest to declare.

First data on the biological variation and quality specifications for plasma ammonia concentrations in healthy subjects

2016 ◽  
Vol 54 (5) ◽  
Author(s):  
Fatma Ucar ◽  
Gonul Erden ◽  
Seyda Ozdemir ◽  
Nurgul Ozcan ◽  
Erdem Bulut ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Plasma Sample ◽  
Biological Variation ◽  
Test Results ◽  
Healthy Individuals ◽  
Variation Data ◽  
Quality Specifications ◽  
Collection Period ◽  
First Time ◽  
Analytical Variation

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.

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