Rapid identification of apolipoprotein E genotypes by multiplex amplification refractory mutation system PCR and capillary gel electrophoresis.
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Apolipoproteins E↗
Biomedical subjects
V Kairisto
Publications and source records attributed to V Kairisto.
Biological day-to-day variation and daytime changes of testosterone, follitropin, lutropin and oestradiol-17beta in healthy men.
Information on biological day-to-day variation is needed for detecting within-subject changes over time. In this study the daytime changes and the biological day-to-day variation of serum testosterone, follitropin, lutropin and oestradiol-17beta concentrations were investigated in 31 healthy males. To analyse daytime changes, blood specimens were taken at 0800 h, 1200 h, 1600 h and 2000 h during one day (n=31) and two days (n=8). The day-to-day variation was analysed from blood specimens collected at 0800 h on days 1 and 2 (n=31) and additionally on days 3, 4, 6 and 9 (n=8). The evaluation of the day-to-day variation was based on calculations of the within-subject (CVA+I) and between-subject (CV(G)) coefficients of variation. When the within-subject day-to-day variances were not too heterogeneous, they were used for the calculation of 95 % reference change limits. Serum testosterone and oestradiol-17beta concentrations showed a significant daytime variation; testosterone had higher serum concentrations at 0800 and 1200 h. A peak in the serum concentration of oestradiol-17beta occurred at 1200 h with a decrease towards the evening. There were no clear daytime changes in the serum concentrations of follitropin or lutropin. For different analytes the reference change limits were: serum testosterone +/- 32.0 %, serum follitropin +/- 24.1 % and serum oestradiol-17beta +/- 38.3 %. The reference change limit was not calculated for serum lutropin, as a high degree of heterogeneity and individuality was found. The interpretation of the results of hormone measurements requires recognition of the biological daytime and day-to-day changes of hormones. The reference change limits determine what changes are significant when monitoring the patient.
Adult↗
Regression-based reference limits and their reliability: example on hemoglobin during the first year of life.
Calculation of reference limits by regression analysis makes it unnecessary to partition the reference data into subgroups, and age-dependent limits can be estimated within as narrow age intervals as necessary. However, the reliability of the regression-based reference limits has not been considered before. To get valid regression-based confidence intervals (CIs) for reference limits, one must evaluate the convolution of two distributions. In this study, age-dependent reference limits with corresponding CIs were produced for blood hemoglobin concentrations over the age interval from newborns to 12 months. We describe how the variance associated with the reference limits can be estimated, and present a Table from which appropriate values can be chosen for the calculation of regression-based reference limits and exact CIs. Also, an equation for the calculation of approximate CIs is given. The data were modeled by linear regression in several cumulative age groups to find the transition zone where the slope changed. After defining this cutoff point, piecewise linear regression was applied. Reference limits and their CIs calculated by conventional and piecewise linear regression methods were almost the same in older age groups but differed significantly during the period of most rapid age-dependent changes, i.e., during the 2 months after birth.
Age Factors↗
Regression-based reference limits: determination of sufficient sample size.
Regression analysis is the method of choice for the production of covariate-dependent reference limits. There are currently no recommendations on what sample size should be used when regression-based reference limits and confidence intervals are calculated. In this study we used Monte Carlo simulation to study a reference sample group of 374 age-dependent hemoglobin values. From this sample, 5000 random subsamples, with replacement, were constructed with 10-220 observations per sample. Regression analysis was used to estimate age-dependent 95% reference intervals for hemoglobin concentrations and erythrocyte counts. The maximum difference between mean values of the root mean square error and original values for hemoglobin was 0.05 g/L when the sample size was > or = 60. The parameter estimators and width of reference intervals changed negligibly from the values calculated from the original sample regardless of what sample size was used. SDs and CVs for these factors changed rapidly up to a sample size of 30; after that changes were smaller. The largest and smallest absolute differences in root mean square error and width of reference interval between sample values and values calculated from the original sample were also evaluated. As expected, differences were largest in small sample sizes, and as sample size increased differences decreased. To obtain appropriate reference limits and confidence intervals, we propose the following scheme: (a) check whether the assumptions of regression analysis can be fulfilled with/without transformation of data; (b) check that the value of v, which describes how the covariate value is situated in relation to both the mean value and the spread of the covariate values, does not exceed 0.1 at minimum and maximum covariate positions; and (c) if steps 1 and 2 can be accepted, the reference limits with confidence intervals can be produced by regression analysis, and the minimum acceptable sample size will be approximately 70.
Child, Preschool↗
Reference intervals for serum thyrotropin, free thyroxine and free triiodothyronine in healthy adults in Finland, measured by an immunoautomate based on time-resolved fluorescence (AutoDELFIA).
We have established reference intervals for healthy adults of serum thyrotropin, free thyroxine and free triiodothyronine using the AutoDELFIA (Wallac, Finland) automatic measuring device. The determination of reference intervals in a proper manner is costly, and many laboratories adopt reference ranges from the literature rather than determining them alone. This is the first report on reference values in thyroidology where this automatic system based on time-resolved fluorescence has been used. The reference intervals for thyrotropin, free thyroxine and free triiodothyronine were 0.6-4.3 mIU/l, 9.6-17.1 pmol/l and 4.3-7.5 pmol/l, respectively.
Adult↗
Estimation of reference change limits using patient data.
Two approaches for deriving reference change limits from patient data are described. In the direct method, hospital database information is used for the selection of appropriate reference groups. If database information is not sufficient or reliable enough, but still most of the source data can be considered as health-related, an indirect method can be applied in the calculation of rough estimates for reference change limits. A computer program developed by us, GraphROC for Windows, includes both methods for the estimation of change limits from patient data. Time between specimen collections should be included as one classifying factor in the selection of source data. When only one previous result is available for comparison, change limits based on the reference sample group form the only available guide for clinical interpretation. However, when several previous results are available and the within-subject variances for the considered analyte are known to be heterogeneous between individuals, the clinical interpretation should rather be based on application of time series analysis.
Data Interpretation, Statistical↗
Software for illustrative presentation of basic clinical characteristics of laboratory tests--GraphROC for Windows.
GraphROC for Windows is a program for clinical test evaluation. It was designed for the handling of large datasets obtained from clinical laboratory databases. In the user interface, graphical and numerical presentations are combined. For simplicity, numerical data is not shown unless requested. Relevant numbers can be "picked up" from the graph by simple mouse operations. Reference distributions can be displayed by using automatically optimized bin widths. Any percentile of the distribution with corresponding confidence limits can be chosen for display. In sensitivity-specificity analysis, both illness- and health-related distributions are shown in the same graph. The following data for any cutoff limit can be shown in a separate click window: clinical sensitivity and specificity with corresponding confidence limits, positive and negative likelihood ratios, positive and negative predictive values and efficiency. Predictive values and clinical efficiency of the cutoff limit can be updated for any prior probability of disease. Receiver Operating Characteristics (ROC) curves can be generated and combined into the same graph for comparison of several different tests. The area under the curve with corresponding confidence interval is calculated for each ROC curve. Numerical results of analyses and graphs can be printed or exported to other Microsoft Windows programs. GraphROC for Windows also employs a new method, developed by us, for the indirect estimation of health-related limits and change limits from mixed distributions of clinical laboratory data.
Clinical Laboratory Techniques↗
Reliability and adequacy of discharge diagnosis databases in the production of reference values.
Discharge diagnoses provide a possibility to select patients individually and then to establish reference values for both "pathological" and control groups. Currently, the available diagnostic information is still at its infancy and should be carefully evaluated before the reference values based on those groups are utilized. It is anticipated that electronic storage of diagnostic and therapeutic information will be applied more commonly in the future as the development of computers makes it easier. The advanced utilization of laboratory data challenges physicians both in the clinical and laboratory side to participate in this development in order to make the information systems serve their actual needs more closely.
Clinical Laboratory Information Systems↗
Effect of platelet count on serum and plasma potassium: evaluation using database information from two hospitals.
The availability of retrospective data from potassium (K+) analyses from two hospitals, one using serum and the other plasma for electrolyte measurements, offered us the possibility to investigate the effect of blood platelet count on serum and plasma K+ concentrations. A weak correlation between plasma K+ and platelet count was observed. The in vitro increase of serum K+ in proportion to the platelet count has clinical significance in conditions, where it may impede the detection of an underlying true K+ disorder. Nomograms and correction factors, based on the correlation between platelet count and serum K+, have been suggested also in some recent reports. In the present study unselected routine patient data was used as source data. The effect of platelet count on the concentration of K+ in serum was lower than reported in previous studies, as indicated by the regression analysis. An increase of 1000 x 10(9)/l in the blood platelet count would cause an increase of about 0.7 mmol/l in the serum K+ concentration (p < 0.0001, r = 0.155). The weak correlation between platelet count and serum K+ does not support the application of platelet-count-based correction of serum K+ level in thrombocytosis. The laboratory should notify the clinician of the significance of the in vitro increase of K+ caused by increased platelet count. K+ should be measured from plasma in such cases.
Artifacts↗
Optimal bin widths for frequency histograms and ROC curves.
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Chemistry, Clinical↗
Generation of reference values for cardiac enzymes from hospital admission laboratory data.
An approach is described for using patient databases of a hospital information system as a source of reference values for cardiac enzymes. Of a total of 2029 emergency admission patients with serial cardiac enzyme data, 538 patients were considered "healthy" (having no damage in myocardium) because their discharge diagnoses suggested neither myocardial damage nor any other condition that could lead to elevated enzyme activities, and because their serially collected cardiac enzyme activities remained stable. Enzyme activities of creatine kinase (EC 2.7.3.2), creatine kinase isoenzyme MB, lactate dehydrogenase (EC 1.1.1.28), and lactate dehydrogenase isoenzyme 1 of these patients at admission to hospital were considered as suitable health related reference values. The upper (97.5%) reference limits of activities, measured at 37 degrees C according to Scandinavian recommendations, were as follows (age dependent limits given at 25 and at 75 years of age, U/l): creatine kinase men 268, 192; creatine kinase women 200 (no age effect); creatine kinase-MB 16, 24; lactate dehydrogenase 497, 603; lactate dehydrogenase isoenzyme 1 103, 140. For comparison, reference values were also produced conventionally from a group of 246 healthy subjects. Observed effects of age on enzyme activities were quite similar to those in the selected patient group. Calculated reference limits for isoenzymes creatine kinase-MB and lactate dehydrogenase isoenzyme 1 were also similar but reference limits for less cardiospecific total enzyme activities, creatine kinase and lactate dehydrogenase, were more variable between these two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Reference intervals developed from data for hospitalized patients: computerized method based on combination of laboratory and diagnostic data.
We utilized the databases of a hospital information system to select for determination of reference values various individual hospitalized patients on the basis of their diagnoses at discharge. The nonparametric 2.5-97.5% "health-related" reference intervals were calculated for hemoglobin concentration, mean corpuscular volume (MCV), and erythrocyte count for both sexes. After excluding patients with diseases possibly affecting erythrocyte variables, we obtained a final group of 1786 women and 1450 men, ages 20-65 years, who were studied in age groups of 20-30, 30-45, 45-55, and 55-65 years. The upper reference limits of the MCV results obtained from hospitalized patients were higher than those produced conventionally from healthy individuals, as would be intuitively suggested by clinical experience. This method, based on selection by diagnosis, could be applicable to various analytes measured in hospital laboratories, provided sufficient data are available as databases.
Adult↗
Method for determining reference changes from patients' serial data: example of cardiac enzymes.
Changes between serial laboratory test results can be significant, even if none of the individual results exceeds the reference interval. We developed a statistical method for the calculation of reference change limits from routine patients' data for situations in which the majority of the patients can be considered suitable reference subjects. The method was applied to cardiac enzyme data [creatine kinase (CK; EC 2.7.3.2), creatine kinase isoenzyme MB (CK-2), lactate dehydrogenase (LD; EC 1.1.1.28), and lactate dehydrogenase isoenzyme 1 (LD-1)] from 2029 consecutive patients. We used hospital discharge diagnoses to exclude patients with the diagnosis of myocardial infarction or myocarditis, but we also studied the characteristics of the method on unselected patients' data. The reference change limits derived from the diagnosis-selected patient group were as follows (U/L, activity measurements in serum at 37 degrees C according to Scandinavian recommendations): CK from -39 to 27, CK-2 from -8 to 7, LD from -86 to 85, and LD-1 from -19 to 15. Similar limits were obtained by conventional statistical methods from a group of 29 hospitalized patients with no myocardial symptoms. Our results suggest that it is possible to produce clinically applicable reference change limits from routine data.
Adolescent↗
Quality control of multichannel hematology analyzers. Bivariate on-line comparison of MCV and MCH values for the detection of random errors.
Volume and hemoglobin content of red blood cells are physiologically interdependent variables but are measured independently in multichannel hematologic analyzers. Therefore correlation of these results to each other can be used as an additional step in internal quality control. To facilitate precise correlation, data were collected from 44,873 consecutive routine determinations of red blood cell parameters. Gaussian distributions were fitted to the original distributions and bivariate elliptical acceptance limits were calculated for simultaneous evaluation of mean corpuscular volume and mean corpuscular hemoglobin results. With the proposed method, rare combinations of the three directly measured red blood cell parameters (hemoglobin, red blood cell count, and mean corpuscular volume) can be identified for the detection of random analytical or preanalytical errors. This mean corpuscular volume-mean corpuscular hemoglobin rule could be added to internal quality-control programs of hematologic analyzers to improve detection of unusual results and possible random errors.
Diagnosis, Computer-Assisted↗
Reference intervals for 24-h urinary normetanephrine, metanephrine, and 3-methoxy-4-hydroxymandelic acid in hypertensive patients.
The urinary excretion of normetanephrine, metanephrine, and 3-methoxy-4-hydroxymandelic acid was quantified by HPLC in hypertensive patients who were being routinely investigated for the exclusion of pheochromocytoma. The data were used to calculate reference intervals for these analytes. Age- and sex-specific 95% reference intervals for 24-h urinary excretion were as follows (mumol/24 h): normetanephrine in men ages 16-35 years (n = 17) 0.7-3.4, in men older than 35 years (n = 121) 0.8-5.1, in women ages 16-35 years (n = 41) 0.5-2.1, and in women older than 35 years (n = 144) 0.6-3.3 mumol/24 h; metanephrine in men (n = 138) 0.3-2.0, and in women (n = 185) 0.2-1.3; and 3-methoxy-4-hydroxymandelic acid in men (n = 142) 10-54, and in women (n = 184) 9-38. Normetanephrine or metanephrine excretion rates or both exceeded the proposed reference intervals in seven of the eight patients with pheochromocytoma. Determination of 3-methoxy-4-hydroxymandelic acid excretion did not yield any additional diagnostic information.
Adolescent↗
Antimicrobial therapy of septicemic patients in intensive care units before and after blood culture reporting.
68 cases of positive blood cultures from 54 intensive care unit (ICU) patients were analyzed retrospectively. The empiric antimicrobial therapy was correct in 65% of the cases as judged by the species and sensitivity of the blood culture isolate. After initial Gram-staining results were known, coverage increased to 77%. After the final blood culture results the coverage was still only 81%. The bacteremia-related mortality was 13%. Although there was no significant difference between the occurrence of bacteremia-related and non-bacteremia-related deaths either in patients with correct or non-optimal empiric treatment, this study emphasizes the need for better utilization of culture reporting. A considerable part of the final blood culture results went unnoticed by the ICU physicians which stresses the importance of good communication between the laboratory and wards.
Adolescent↗