Reference values in medicine and validity of diagnostic test.
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PURPOSE: To determine the reproducibility and the normal reference range of pulsatile ocular blood flow (POBF) values in healthy subjects using the Ocular Blood Flow Tonograph (OBF Laboratories, UK Ltd., Wiltshire, England). METHOD: Pulsatile ocular blood flow was measured in one eye of each of 83 patients. Coefficient of reliability was determined by calculation of intraclass correlation coefficient via one-way analysis of variance. Mean difference between measurements was calculated for bias and first exposure effects. Pulsatile ocular blood flow from 163 healthy individuals were analyzed to determine the distribution, mean, standard deviation (SD), range, and the 5th and 95th percentile values. The influence of age, blood pressure, pulse rate, and intraocular pressure on pulsatile ocular blood flow was determined by regression analysis. RESULTS: Reliability coefficient for pulsatile ocular blood flow values ranging from 290 microliters/min to 2,196 microliters/min was 0.92. Variation in bias and first exposure effect were not significant. Pulsatile ocular blood flow values were normally distributed. Mean values were 669.90 +/- 233.0 microliters/min in men and 841.90 +/- 254.6 microliters/min in women. Fifth and ninety-fifth percentile values were 364.75 microliters/min and 1,266.10 microliters/min in men and 397.18 microliters/min and 1,346.10 microliters/min in women. Pulsatile ocular blood flow was significantly influenced by pulse rate. CONCLUSION: This study confirms the reliability of the Ocular Blood Flow Tonograph in repeated measurements of POBF within individuals over short time intervals. The high interindividual variation in POBF may invalidate comparison of POBF between individuals, and the wide range of normal values may limit the value of using a low POBF as a possible indicator of disease.
The authors give biological reference figures obtained from 106 fetuses that were sampled in utero between the 20th and 34th week of amenorrhoea. These fetuses were considered to be normal because there was no clinical or ultrasound evidence of an abnormality. Furthermore the biological values sought in antenatal testing and the absence of all pathology in the first year of life, confirmed that these were normal fetuses. The result has been expressed as a global figure for all 106 fetuses; then they have been divided up according to the gestational age groups (20-23, 24-27, and 28-34 weeks of amenorrhoea). These biological reference values and their changes as the age of the fetuses advanced are discussed and compared with the figures reported in the literature.
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The majority of the published reference range data on catecholamines excretion by healthy children is incomplete and often contradictory (1). We assayed in the urines of 127 healthy children the values of the catecholamines (norepinephrine, epinephrine, dopamine) and their methylated metabolites (normetanephrine, metanephrine, 3-methoxytyramine) for the determination of paediatric reference ranges. Data were expressed as micrograms/24 h, mumol/24 h and mmol/mol creatinine. An isocratic HPLC procedure by ion-pair reversed phase chromatography on a C18 column, using a single mobile phase containing formic acid, acetonitrile, diethylamine and octane sulphonic acid (ion pairing agent), permitted the separate assay of the various fractions of total catecholamines. The relations between each biogenic amine and age were studied and reference values were determined as a function of age.
Since the introduction of fully automated nephelometric systems simultaneous measurements of immunoglobulin light chains kappa (kappa) and lambda (lambda) and IgG, IgA and IgM have become increasingly used for the routine assessment of humoral immunity. From these data two ratios were calculated, the kappa/lambda ratio and the heavy chains to light chains ratio. As changes in these ratios might have some predictive clinical value besides reflecting a monoclonal component, it is necessary to know mean and reference limits of these ratios. On account of differences in the calibration method of the light chains measurements (either free light chains or light chains bound to a complete molecule) and of differences in the calculation method of the heavy chains to light chains ratio we were led to conduct our own investigation. IgG, IgA and IgM and kappa and lambda light chains were immunonephelometrically measured in the sera of 84 blood donors. For each sample theoretical values for kappa + lambda, kappa and lambda, and kappa/lambda were calculated using the existing relation between the concentration of a given immunoglobulin and the concentration of bound light chains. Using the Valtec Protocole and the t test we were able to evidence highly significant differences (p < 10(-4) between theoretical and experimental values of kappa, lambda and kappa + lambda; those differences could be proved to be directly linked to the nephelometric technique itself. However the experimental kappa/lambda ratio did not appear to differ from the theoretical one nor the standardization method to have an effect on the reference values of this ratio, our values (mean and reference limits, 1.81, 1.29-2.53) being very similar to previously published results. Concerning the so called heavy chains to light chains ratio two methods were used to express it, one consisting in the ratio of the theoretical kappa + lambda value to the experimental one with the following results, 1.05 and 0.93-1.18 for the mean and reference limits and the other one using the raw data. The results were as follows: mean 3.50, reference limits 3.11-3.94.
OBJECTIVES: Normal lung function has been shown to be population specific. The aim of this study was to derive normal reference spirometric values for Omani children and adolescents. METHODOLOGY: Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), peak expiratory flow and forced mid-expiratory flow were measured in 837 healthy Omani school children aged 6-19 years. Multiple linear regression analysis was performed for each spirometric parameter against age, height and weight for boys and girls separately. RESULTS: All measured spirometric parameters increased with age and height and were significantly higher in boys than girls. Height explained the maximum variance for all parameters. After accounting for height in the prediction equations, the contribution of age and weight was minimal. The expiratory ratio (FEV(1)%FVC) was independent of age and height and its mean values (+/- standard deviation) were slightly higher in girls (91.1 +/- 6.1%) than boys (86.5 +/- 7.1%; P < 0.001). The predicted normal values of the subjects using the derived equations were between 5 and 10% lower than the respective values for subjects in Caucasian sample groups. CONCLUSION: The developed prediction equations can be used in clinical practice in Oman and can be considered for use in neighbouring Arab countries.
Random urine samples were collected from 305 children aged from birth to 14 years and the values of hydroxymethoxymandelic acid, homovanillic acid, noradrenaline, adrenaline, and dopamine were measured by high-performance liquid chromatography with electrochemical detection. The results were reported relative to the urinary creatinine concentration and the values declined progressively with increasing age for each analyte with the exception of adrenaline. The results for each age group were not normally distributed and all values except outliers were retained in determining the upper reference limits.
BACKGROUND: To be able to interpret laboratory values, it is essential to develop population-based reference intervals. A crucial consideration is whether a reference interval should be divided into subpopulations or not, so-called partitioning. There are established methods for deciding whether partitioning should be done or not. However, these methods are only applicable when partitioning into two subpopulations is considered. The primary aim of this study was to suggest a procedure that was also valid for several subpopulations. The method assumes that these subpopulations are Gaussian. Furthermore, a secondary aim was to provide a tailor-made computer program to support calculations. METHODS: The fundamental idea is to partition reference intervals if the proportions of the distributions of the subpopulations outside the combined reference limit deviate from the nominal value of 0.025. This is made possible by finding the combined reference interval using an equation solver algorithm. RESULTS: It was found that an equation solver algorithm could easily identify the combined reference interval when combining two or more subpopulations, even if these subpopulations had unequal prevalences. It was also found that this could be done even if the ratio between samples does not reflect the ratio between prevalences. Using this algorithm, it was possible to study whether the proportion outside the combined reference limits in any of several subpopulations deviated from the nominal 0.025 by such a magnitude that partitioning was recommended. When similar figures to those found in earlier studies with other methods were tested, the procedure showed consistent results with these methods. The procedure was also found to be applicable when several subpopulations were considered. As a practical result of the study, a tailor-made computer program was developed and is now provided over the Internet. CONCLUSIONS: The suggested procedure could serve as an alternative or complement to existing methods. The procedure provides calculations of the combined reference interval, even if sample fractions do not reflect prevalence fractions. The important advantage with the suggested procedure is the generalisation to the situation when several Gaussian subpopulations, possibly with unequal prevalences, are considered. Finally, since a tailor-made computer program is provided, the procedure is simple to use.
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OBJECTIVE: To construct reference ranges of orbital diameters, measured in early pregnancy by transvaginal sonography. METHODS: The study group consisted of 2717 fetuses of pregnant women referred to our center and examined by transvaginal ultrasound between 11-16 week's gestation. Nomograms with confidence intervals (5th and 95th percentile) for each orbital measurement (orbital diameter, interocular and binocular distance) versus gestational age were produced. RESULTS: The orbital measurements increased in a linear fashion throughout early pregnancy with a good correlation with gestational age. CONCLUSION: Transvaginal sonography is able to visualize and measure orbital diameters with accuracy in early pregnancy; reference ranges were developed that can be used to evaluate normal orbital development and can be helpful in the detection of syndromes with orbital growth defects and other associated fetal anomalies.
To establish accurate reference ranges for the entire second trimester, we documented organ weights, body weight, and linear measurements for 597 fetuses and neonates with gestational ages ranging from 12 to 26 wk. We determined the mean and standard deviation for weights and measurements at each week of gestation using the StatView trade mark SE + Graphics statistical program. The analyses revealed a linear correlation between the gestational age and, respectively, the toe-heel length, crown-rump length, and crown-heel length. Body and organ weights increase at varying rates throughout the second trimester. The data correlate well with weights and measurements previously published for the latter half of the second trimester, and extend these reference ranges to encompass the entire second trimester.
OBJECTIVES: To calculate reference ranges for fetal limb measurements obtained by transabdominal ultrasound at 10-14 weeks of gestation. METHODS: Six hundred and six normal fetuses were examined transabdominally in a cross-sectional study by a single observer. The crown-rump length of the fetuses ranged from 31 to 78 mm. Measurement of the length of the humerus, ulna, femur, tibia and foot was attempted from the longest section of each structure. To assess intraobserver repeatability, three sets of repeated measurements were obtained in 26 fetuses. RESULTS: An appropriate ultrasound measurement was obtained in a percentage of cases ranging from 93.2% to 97.9%. A significant correlation was found between crown-rump length measurements and humerus length (r = 0.74, P < 0.001), ulna length (r = 0.70, P < 0.001), femur length (r = 0.77, P < 0.001), tibia length (r = 0.69, P < 0.001) and foot length (r = 0.58, P < 0.001). Crown-rump length-specific reference ranges for each measurement were calculated with the method of scaled absolute residuals. The study of intraobserver variability showed coefficients of variation ranging from 7.9 to 10.0% and intraclass correlation coefficients ranging from 0.89 to 0.94. CONCLUSIONS: Fetal limb size is strongly correlated with crown-rump length. Despite a significant biological variability of the measurements, the availability of reference ranges could be of help in the early diagnosis of fetal skeletal dysplasias.
Reference ranges for each cell type and six different ratios (M : E ratio = quotient of number of myeloid cells/erythroid precursors; different maturation ratios) were calculated for bone marrow aspirates of adult dogs. These values were based on 2.5 and 97.5% percentiles of differentials of 1000 cells in bone marrow aspirates of 92 healthy 1-8-year-old dogs. The results of intact male and female dogs were compared. No distinct sex-related differences were found (P > 0.05). A wide physiological range was observed in almost all bone marrow cells resulting in broad reference ranges for the ratios. The clinically relevant M : E ratio varied between 0.45 and 2.87. The accurate cytological examination of bone marrow based on the reference ranges presented in this study requires preparation of high-quality bone marrow films with minimal blood contamination.