Biological and Analytic Components of Variation in Long-Term Studies of Serum Constituents in Normal Subjects

1970 ◽  
Vol 16 (12) ◽  
pp. 1028-1032 ◽  
Author(s):  
Ernest Cotlove ◽  
Eugene K Harris ◽  
George Z Williams

Abstract Biological components of variation for each of 15 serum constituents have been estimated in 68 normal subjects by weekly measurements over several months, and concurrent measurements on invariant human serum pools. Intra-individual coefficient of variation was smallest, less than 2%, for Na, Cl, Ca, Mg; 3 to 4% for CO2, albumin, and total protein; 5 to 7% for K, glucose, cholesterol, and phosphate; and largest, 9 to 12%, for uric acid, urea nitrogen, SGOT, and LDH. Inter-individual variation was larger than intra-individual variation for all 15 tests except Cl, CO2, and K. Analytic deviation was as large as or larger than biological (intra- or inter-individual) variability for constituents, such as calcium, which are under precise homeostatic control, thus producing artifactual widening in the observed normal range and obscuring the borderline between normal and abnormal results. Limits of tolerable variability in laboratory procedures are proposed, based on composite intra- and inter-individual variation, that would permit medically significant deviations in results to be detected. Such limits were exceeded by current methodology in at least half the 15 tests.

1970 ◽  
Vol 16 (12) ◽  
pp. 1022-1027 ◽  
Author(s):  
Eugene K Harris ◽  
Paul Kanofsky ◽  
George Shakarji ◽  
Ernest Cotlove

Abstract Standard statistical analysis of variance has been used on data from weekly determinations of 15 blood constituents in each of 68 normal subjects, our purpose being to isolate and estimate biological components of observed variation. These components include intra-individual, or "personal" variation, and inter-individual, or "group" variation. The most critical problem, that of separating personal variation from long-term analytic deviations in each individual's data record, was resolved with the aid of concurrent analysis of a constant "pooled" serum. Comparison of isolated personal variation with inter-individual variation indicates that many common blood tests—e.g., magnesium, calcium, total protein, uric acid, serum enzymes, and cholesterol—could contribute to an individually distinctive blood "profile" if substantial improvements were made in analytic precision. Presently, only cholesterol (among older women) and uric acid (in males) appear to possess strong capabilities for distinguishing among normal individuals.


1971 ◽  
Vol 17 (10) ◽  
pp. 983-987 ◽  
Author(s):  
Eugene K Harris ◽  
David L DeMets

Abstract Intra- and interindividual components of variation in ionized calcium among normal individuals have been estimated. The basic data were means of duplicate analyses of total serum calcium, total serum protein, and serum albumin from 68 normal subjects, 10-12 weekly samples per person. The McLean-Hastings equation was used to estimate [Ca2+]. Use of observed albumin/globulin ratios, instead of an assumed constant, had negligible effect on mean [Ca2+] or components of variation. The interindividual component of variation in [Ca2+] was found to be the same as that in total calcium: 3%. Average intraindividual variation (0.045-0.05 mmol/liter), appeared to be entirely attributable to analytical deviations in total protein and total calcium determinations. Thus, in the average normal individual, no physiologic variation in [Ca2+] could be detected. Results agreed with recent data on [Ca2+] measured by calcium ion-selective electrodes.


1998 ◽  
Vol 173 (4) ◽  
pp. 341-344 ◽  
Author(s):  
Martin Kurz ◽  
M. Hummer ◽  
G. Kemmler ◽  
I. Kurzthaler ◽  
A. Saria ◽  
...  

BackgroundPrevious studies of clozapine pharmacokinetics have shown a wide intra- and inter-individual variability of plasma levels in patients on stable clozapine doses. We investigated dose-plasma level relationships and intra-individual variability of plasma levels during maintenance treatment with clozapine.MethodForty-one patients on clozapine were followed for 26 weeks with repeated plasma level measurements and assessments of co-medication and clinical symptoms. In a second step, 15 patients on stable clozapine doses between treatment Weeks 12 and 52 were followed in the same way. Coefficient of variation was used as a parameter of plasma level deviation.ResultsDose-plasma level correlations stayed significant from Week 6 to Week 26 (n=41). The group of patients followed up to Week 52 showed a mean intra-individual coefficient of variation of 52.8% (s.d. =20.6), and remained stable psychopathologically.ConclusionsEven though clozapine plasma levels may show a significant degree of variation, this is not necessarily reflected in a change in psychopathology.


Author(s):  
Akotegnon Rodrigue ◽  
Michodjehoun Loetitia ◽  
Behanzin Justin ◽  
Houeze Elisabeth ◽  
Sezan Alphonse

The aim of this study was to evaluate the impact of the ethyl extract of dried leaves of Hexalobus monopetalus on protein metabolism in Wistar rats. After a phytochemical screening of extracts, total protein, urea, uric acid and creatinine were measured spectrophotometrically at six (06) sets of three (03) Wistar rats each. Batches 2 to 6 were given with orally administered respectively the daily doses of: 0.25 mg / kg, 0.5mg / kg, 1mg / kg, 1.5mg / kg and 2.5mg kg body weight of the extracts (for 14 days). The lot1 witness received distilled water instead of the extract. The results of the phytochemical screening revealed the presence polyphenolic compounds (gallic tannins, catechin tannin or condensed, anthocyanins, and leuco anthocyanins), flavonoids, mucilages reducing compounds, alkaloids, certain anthracene derivatives ( free anthracene, the O-glycosides), Steroids, and quinone derivatives. It was observed a significant increase (p ˂ 0.05) blood levels of total protein and uric acid and a significant (p ˂ 0.05) blood urea and creatinine levels in treated plots to extracts. These observed variations did not depend on the administered dose of the extracts but were depending on the duration of treatment; they were outstanding from the 7th day of treatment. The long term use of ethyl extract of dried leaves of Hexalobus monopetalus could compromise the liver function and the kidneys and may inhibit apoptosis in Wistar rats.


1986 ◽  
Vol 32 (12) ◽  
pp. 2201-2203 ◽  
Author(s):  
J M Hicks ◽  
M Iosefsohn

Abstract We evaluated the Kodak DT60 analyzer, to assess its suitability for use in the physician's office setting. The DT60 Analyzer is based on the same multilayer film technology as used in the Ektachem 400 and 700. We compared results obtained with DT60 for all the analyses currently available for use in this instrument (Na+, K+, Cl-, glucose, urea nitrogen, uric acid, total bilirubin, total protein, amylase, cholesterol, and triglycerides) with results from a Kodak Ektachem 700 Analyzer and from other laboratory procedures. Results for hemoglobin were compared with those from a Coulter Counter Analyzer. For all analytes, linearity of the standard curve for various dilutions of Ektachem calibrators was within the manufacturer's claims. CVs for within-run precision ranged from 0.8% to 5.4%, run-to-run CVs ranged from 1.6% to 7.5%. Except for amylase, comparisons with other methods were generally very good. The only interference we observed was that of hemoglobin in the bilirubin assay. Calibration was stable for longer than one month. We also compared the performance of a skilled operator with that of an unskilled operator and of a physician.


1970 ◽  
Vol 16 (12) ◽  
pp. 1016-1021 ◽  
Author(s):  
George Z Williams ◽  
D S Young ◽  
Mervyn R Stein ◽  
Ernest Cotlove

Abstract A study of blood constituents in normal individuals was undertaken to (a) estimate the contribution of biological and analytical factors to the variation of constituents over an extended time period; (b) to explore whether such tests can be used to derive meaningful personal blood "profiles"; and (c) to determine when analytic variation may become large enough to assume medical significance. This first paper describes procedures for subject selection, the laboratory methods employed, and evaluates analytic standard deviations. A group of 68 normal subjects was selected after medical evaluation. Sera were collected and analyzed in duplicate weekly for 10 to 12 weeks. Analytic deviation was estimated from the results of concurrent daily analyses of sterile pools of human serum. Laboratory procedures were introduced to reduce analytic deviation and to allow more accurate estimation of biological components of variation within and among individuals.


1976 ◽  
Vol 22 (6) ◽  
pp. 837-842 ◽  
Author(s):  
J I Routh ◽  
W D Paul

Abstract We have assessed the interference of acetylsalicylic acid (aspirin) with some common clinical laboratory assays, because of its widespread use and reported interference. The therapeutic regimens involved ingestion of 10 325-mg tablets daily for three days or eight tablets for five days or two weeks. Twenty-one commonly done determinations were run on control sera, and sera were collected during and after drug therapy. Significant changes in t-test values, indicating the significance of the standard deviation of the difference between controls and specimens drawn after drug therapy, were observed for chloride (increased), and for total protein, calcium, cholesterol, uric acid, bilirubin, and thyroxine (decreased). Aspirin therapy depressed the apparent concentrations of these constituents progressively in the three-day regimen and initially in the long-term regimens, followed by recovery toward zero t-values at the end of the longer regimens.


1979 ◽  
Vol 91 (3) ◽  
pp. 397-409 ◽  
Author(s):  
Antonino Barbarino ◽  
Laura de Marinis ◽  
Edoardo Menini ◽  
Carmelo Anile ◽  
Giulio Maira

ABSTRACT Twenty women with hyperprolactinaemia secondary to a pituitary adenoma were studied before and after selective transsphenoidal removal of the tumour. Pre-operatively, thyrotrophin-releasing hormone (TRH) (200 μg iv) and metoclopramide (MCP) (10 mg po) did not produce a positive PRL response in the tumour patients. By contrast, 14 post-partum lactating women, who were used as controls, exhibited a positive response to MCP administration. Methergoline (4 mg po) was shown to decrease serum PRL levels in 8 normal subjects, in 6 puerperal women, and 9 of 10 tumour patients. Bromoergocriptine (CB-154, 2.5 mg po) decreased serum PRL levels in 10 tumour patients. Following transsphenoidal removal of the adenoma serum PRL levels were reduced in all patients, and returned to normal in 14 patients. Prognostics for completely normalizing PRL secretion after transsphenoidal surgery is better when initial serum PRL levels are below 200 ng/ml. After surgery all hyperprolactinaemic patients failed to show a positive PRL response to TRH and MCP. Nine normoprolactinaemic patients had a positive response to both stimuli while 3 patients failed to show a positive response immediately following surgery. Long-term studies, however, showed that a positive PRL response was obtained in all patients tested 8–14 months after treatment. A positive PRL response to methergoline and bromocriptine was observed post-operatively in the patients tested regardless of their basal PRL level. Data from this study indicate that surgically proven PRL-secreting adenomas are invariably associated with negative PRL responses to TRH and MCP. The normalization of the prolactin regulation after surgery points toward the intrapituitary localization of the lesion associated with PRL-secreting adenomas.


Author(s):  
A. B. Nazarenko ◽  
O. I. Sebezhko ◽  
V. A. Andreeva ◽  
T. V. Konovalova ◽  
O. S. Korotkevich ◽  
...  

The paper shows the results of biochemical analysis of the protein status of Kemerovo pigs. The research was carried out at OOO Chistogorskiy in Kuzbass. The blood samples from pigs were taken by means of the standard methods and analyzed in the laboratory of veterinary genetics and biochemistry of Novosibirsk State Agrarian University. The researchers used standard tools for biochemical tests on the biochemical semi-automatic analyzer Photometer 5010 V5+. The concentration of some protein metabolic parameters was characterized by a standard distribution: total protein (p-value=0.85), albumin (p-value=0.06), and globulin (p-value=0.65). The average values of total protein and albumins varied in standard intervals, except for the level of globulins, which was significantly lower than the reference values set for pigs. It was seen as one that had the greatest individual fluctuations (44%). The urea concentration was slightly lower than the physiological standard and was characterized by a rather high level of individual variability (50%). The researchers found that uric acid concentration was 3.2 times lower than the standard one in the investigated pigs. The authors observed the interbred differences in the content of total protein and albumin comparing the Kemerovo, Chistogorsk and early maturing pig breeds (CM-1). The correlation analysis has shown that there is a high positive correlation between total protein and globulins (r=0.88). The average positive relation between urea and uric acid was (r=0.58). The obtained data on protein metabolism is one of the basic characteristics of the Kemerovo pigs interior.


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