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Determination of reference ranges for elements in human scalp hair.

Expected values, reference ranges, or reference limits are necessary to enable clinicians to apply analytical chemical data in the delivery of health care. Determination of references ranges is not straightforward in terms of either selecting a reference population or performing statistical analysis. In light of logistical, scientific, and economic obstacles, it is understandable that clinical laboratories often combine approaches in developing health associated reference values. A laboratory may choose to: 1. Validate either reference ranges of other laboratories or published data from clinical research or both, through comparison of patients test data. 2. Base the laboratory's reference values on statistical analysis of results from specimens assayed by the clinical reference laboratory itself. 3. Adopt standards or recommendations of regulatory agencies and governmental bodies. 4. Initiate population studies to validate transferred reference ranges or to determine them anew. Effects of external contamination and anecdotal information from clinicians may be considered. The clinical utility of hair analysis is well accepted for some elements. For others, it remains in the realm of clinical investigation. This article elucidates an approach for establishment of reference ranges for elements in human scalp hair. Observed levels of analytes from hair specimens from both our laboratory's total patient population and from a physician-defined healthy American population have been evaluated. Examination of levels of elements often associated with toxicity serves to exemplify the process of determining reference ranges in hair. In addition the approach serves as a model for setting reference ranges for analytes in a variety of matrices.

Adolescent↗

Analyses with the KODAK-Ektachem. Accuracy control using reference method values and the influence of protein concentration. Part II. Substrates.

The reliability of the determination of the most common substrates with the Ektachem 700 was evaluated. Accuracy control was performed in various ways including the comparison of results with reference method values. The influence of protein concentration was investigated systematically using sera containing varying amounts of protein obtained by ultracentrifugation. Bilirubin. Deviation from the reference method values was within limits of the guidelines (Dt. Arztebl. 85 (1988) B517-B532). The influence of protein concentration was negligible. Cholesterol. The results agreed well with the reference method values. The method was not influenced by different protein concentrations. Creatinine. The results were in good agreement with reference method values, when the method was calibrated with the primary assigned values of the calibrators. At high protein concentrations, the results were higher than those of the comparative method. Glucose. The mean deviation from the reference method values was 1.0%. There was a clear positive bias at high protein concentrations. Protein. The results from the Ektachem deviated from the reference method values by -6.8%. Total glycerol (triacylglycerols). In the analysis of control sera, the Ektachem values differed greatly (+32.1%) from the reference method values. This difference was not found in a comparative study with native sera. At high protein concentrations the Ektachem results were higher than those of the comparative method. Urea. The results were lower than the method-dependent assigned values (-16.6%). This deviation was not observed in a comparative study with native sera. Interference by protein was not observed. Uric acid. In accuracy control with reference method values, a small bias was observed (+3.3%), which increased at high protein concentrations.

Bilirubin↗

A comparison of reference method values for calcium, lithium and magnesium with method-dependent assigned values.

Commercially available control sera were analysed by the reference methods for calcium, lithium and magnesium. Calcium: The mean deviation of the target values for routine flame atomic absorption spectrometry from the reference method values was -1.2%, in the case of flame atomic emission spectrometry -0.1%. The assigned values of determinations by methylthymol blue and cresolphthalein showed a positive bias: +2.3 and +2.2%. Lithium: Target values for routine flame atomic absorption spectrometry and flame atomic emission spectrometry were in generally good agreement with the reference method values (deviation +1.7% and +0.7%), although the differences were dependent on concentration. Magnesium: The assigned values for routine flame atomic absorption spectrometry yielded a mean bias of -0.4% from the reference method value. The target values for absorption spectrometry after reaction with Magon and Calmagite, however, differed by +8.2% and +9.3% on average. These methods seem to be less suitable for the determination of magnesium in serum than FAAS and would have failed several times to meet the requirements of quality assessment.

Calcium↗

Spatial distribution of trace metals in sediments from urban streams of Semarang, Central Java, Indonesia.

Elevated environmental concentrations of metals are usually associated with the impact of urbanization. The present study is focused on metal contamination in urban sediments. A field survey was carried out to determine the distribution of four metals, i.e., cadmium (Cd), lead (Pb), copper (Cu), and zinc (Zn), in the coastal urban area of Semarang, Central Java, Indonesia. Sediment samples were collected from 101 grids of 2x2 km. To map the spatial distribution of these metals, concentrations of each metal were plotted against the corresponding grid coordinate. Cd was below the detection limit (<0.03 microg/g) in all samples, whereas concentrations of Pb, Zn, and Cu fell into a wide range. Frequency distributions of Pb, Zn, and Cu concentrations indicated a similar pattern, in which the major proportion of the sites had a low metal concentration. Some sites, however, had extremely high metal concentrations, Zn up to 1257 microg/g, Pb up to 2666 microg/g, and Cu up to 448 microg/g. The data were used to define background concentrations for sediments in coastal zones of Indonesia ("reference values"). The proposed reference values are 25.6 microg/g, 132.2 microg/g, and 40.7 microg/g, respectively, for Pb, Zn, and Cu. The degree of metal contamination of each individual site was classified according to the calculated value of a combined pollution index, W. Four categories of the degree of metal contamination were proposed, i.e., unpolluted, slightly polluted, polluted, and heavily polluted. Based on this classification, from 101 sites investigated in the greater Semarang area, 51 are unpolluted, 36 slightly polluted, 9 polluted, and 5 heavily polluted.

Cadmium↗

100 or 30 years after Janeway or Bartter, Healthwatch helps avoid 'flying blind'.

Longitudinal records of blood pressure (BP) and heart rate (HR) around the clock for days, weeks, months, years, and even decades obtained by manual self-measurements (during waking) and/or automatically by ambulatory monitoring reveal, in addition to well-known large within-day variation, also considerable day-to-day variability in most people, whether normotensive or hypertensive. As a first step, the circadian rhythm is considered along with gender differences and changes as a function of age to derive time-specified reference values (chronodesms), while reference values accumulate to also account for the circaseptan variation. Chronodesms serve for the interpretation of single measurements and of circadian and other rhythm parameters. Refined diagnoses can thus be obtained, namely MESOR-hypertension when the chronome-adjusted mean value (MESOR) of BP is above the upper limit of acceptability, excessive pulse pressure (EPP) when the difference in MESOR between the systolic (S) and diastolic (D) BP is too large, CHAT (circadian hyper-amplitude tension) when the circadian BP amplitude is excessive, DHRV (decreased heart rate variability) when the standard deviation (SD) of HR is below the acceptable range, and/or ecphasia when the overall high values recurring each day occur at an odd time (a condition also contributing to the risk associated with 'non-dipping'). A non-parametric approach consisting of a computer comparison of the subject's profile with the time-varying limits of acceptability further serves as a guide to optimize the efficacy of any needed treatment by timing its administration (chronotherapy) and selecting a treatment schedule best suited to normalize abnormal patterns in BP and/or HR. The merit of the proposed chronobiological approach to BP screening, diagnosis and therapy (chronotheranostics) is assessed in the light of outcome studies. Elevated risk associated with abnormal patterns of BP and/or HR variability, even when most if not all measurements lie within the range of acceptable values, becomes amenable to treatment as a critical step toward prevention (prehabilitation) to reduce the need for rehabilitation (the latter often after costly surgical intervention).

Chronotherapy↗

Procalcitonin and C-reactive protein kinetics in postoperative pediatric cardiac surgical patients.

OBJECTIVE: To determine the kinetics of procalcitonin (PCT) and C-reactive protein (CRP) concentration after pediatric cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, clinical cohort study. SETTING: A fifteen-bed tertiary-care pediatric intensive care unit. PATIENTS: Fourteen pediatric patients admitted for cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Serum PCT and CRP were measured before cardiopulmonary bypass (CPB); after CPB; and on the first, second, and third days after surgery by means of immunoluminometry and nephelometry, respectively. Reference values for systemic inflammatory response syndrome are 0.5 to 2.0 ng/mL for PCT and <5 mg/L for CRP. Baseline serum PCT and CRP concentrations were 0.24 +/- 0.13 ng/mL and 4.06 +/- 3.60 mg/L (median 25th percentile-75th percentile), respectively. PCT concentrations increased progressively from the end of CPB (0.62 +/- 0.30 ng/mL), peaked at 24 hours postoperatively (POD1) (0.77 +/- 0.49 ng/mL), and began to decrease at 48 hours or POD2 (0.35 +/- 0.21 ng/mL). CRP increased just after CPB (58.82 +/- 42.23 mg/L) and decreased after 72 hours (7.09 +/- 9.81 mg/L). CONCLUSION: An increment of both PCT and CRP was observed just after CPB. However, PCT values remained within reference values, whereas CRP concentrations increased significantly after CPB until the third day. These preliminary results suggest that PCT was more effective than CRP to monitor patients with SIRS and a favorable outcome.

Analysis of Variance↗

Analyses with the KODAK-Ektachem. Accuracy control using reference method values and the influence of protein concentration. Part I. Electrolytes.

The reliability of electrolyte determinations with the Ektachem 700 was evaluated by various means including the use of reference method values. The influence of protein concentration, which may alter the viscosity and hence the speed of diffusion, was systematically investigated by using samples of varying protein concentration obtained by ultracentrifugation. Calcium. The mean bias between Ektachem results and reference method values of 9 control sera was -7.3%. In a comparative study with native sera a negative bias was not obtained. The accuracy was independent of the protein concentration. Chloride. The mean bias was -0.1% compared with reference method values. As might be expected, the difference between chloride values with Ektachem--using a "direct" ion-selective electrode--and determinations by coulometry increased with increasing protein concentrations. Magnesium. A negative bias (-5.0%) was obtained in accuracy control with reference method values, and to a smaller extent in a comparative study with native sera. An influence of the protein concentration on the magnesium determination was not observed. Phosphate. Accuracy control by method-dependent assigned values and a comparative study with native sera showed a positive bias. Ektachem results depend on the protein concentration. At 120 g/l protein the bias was +13.6%. Potassium. The mean bias, with respect to reference method values, was -1.2%. At high concentrations of proteins of "normal" composition, Ektachem results agree with measurements by flame atomic emission spectrometry; in paraproteinaemic sera the values are higher. Sodium. The mean inaccuracy was 3.3%, compared with reference method values. The dependence on the amount and composition of the total protein was similar to that found for potassium analysis.

Blood Chemical Analysis↗

Artificial neural network analysis: a novel application for predicting site-specific bone mineral density.

Dual X-ray absorptiometry (DXA), which is the most commonly used method for the diagnosis and followup of human bone health, is known to produce accurate estimates of bone mineral density (BMD). However, high costs and problems with availability may prevent its use for mass screening. The objective of the present study was to estimate BMD values for healthy persons and those with conditions known to be associated with BMD, using artificial neural networks (ANN). An ANN was used to quantitatively estimate site-specific BMD values in comparison with reference values obtained by DXA (i. e. BMD(spine), BMD(pelvis), and BMD(total)). Anthropometric measurements (i. e. sex, age, weight, height, body mass index, waist-to-hip ratio, and the sum of four skinfold thicknesses) were fed to the ANN as independent input variables. The estimates based on four input variables were generated as output and were generally identical to the reference values for all studied groups. We believe the ANN is a promising approach for estimating and predicting site-specific BMD values using simple anthropometric measurements.

Bone Density↗

The relationship between heart rate and QT interval during atrial stimulation.

The relationship between heart rate and QT interval was investigated during atrial stimulation (intrinsic effect of heart rate) in ten healthy male volunteers prior to and after administration of sotalol. The QT interval in the ECG (paper speed 200 mm/s) was determined at rates of 70, 85, 100, 115, 130, 145, and 160 beats/min and at pacing periods of 180 s each at 30, 60, 120, and 180 s. After a 15-minute period, 2.0 mg sotalol/kg body weight were administered iv and the stimulation protocol was repeated. The analysis of QT interval behavior reveals contradictions to the mathematical implications of Bazett's equation QT = QTc square root of 60/HR, so that the relationship between heart rate and QT interval is not adequately described under the given conditions. After examination of approaches reported in the literature and our own approaches, the expression QT = a e-b (HR-60) is used as a possibility differentially to describe the data by nonlinear regression. The parameters a and b may be interpreted as QT reference value and shortening parameter. The QT reference value a, a parameter in reference to heart rate of 60 beats/min, has a comparable significance to the expression QTc in the Bazett equation. A reduction in the shortening parameter b indicates whether substances influencing the QT interval additionally produce overproportional shortening of the QT interval with increasing heart rate. After administration of sotalol, an increase can be observed in both the QT reference value and also in the shortening parameter. The suggested approach is an attempt to provide a more precise assessment of the QT interval under different conditions.

Adult↗

Delayed elevation of soluble tumor necrosis factor receptors p75 and p55 in cerebrospinal fluid and plasma after traumatic brain injury.

Recent studies have reported a significant inflammatory reaction in the brain and the systemic circulation after traumatic brain injury (TBI). Although there is growing knowledge and understanding of the mechanisms and mediators involved in the proinflammatory reaction, little is known about the anti-inflammatory mediators in the brain. As tumor necrosis factor alpha (TNF-alpha) plays a detrimental role in the initiation and promotion of the proinflammatory reactions after TBI, the endogenous scavenger system, represented by the soluble TNF receptors (sTNFRs) p55 and p75, seems to have an important anti-inflammatory capacity by binding to circulating TNF-alpha. To evaluate this potentially anti-inflammatory response to trauma, we analyzed sTNFR p55 and p75 in paired plasma/cerebrospinal fluid (CSF) samples of 29 patients who encountered TBI. Values were compared with reference values obtained from healthy volunteers (n = 91). Patients with TBI showed significantly (P < 0.001) elevated sTNFR p55 and p75 values starting from day 2 and lasting until day 10 if compared with reference values. In contrast to the early increased plasma values p55 and p75 showed slowly increasing CSF values starting on day 4 and 3, respectively. Significantly (P < 0.001) increased CSF values of p 55 were determined on days 4 to 6 and day 9. p75 showed significantly (P < 0.001) elevated values if compared with control values on days 7 and 9. The sTNFR p55 and p75 show a distinct and long-lasting elevation in plasma of patients after TBI. In contrast, CSF values display a delayed and less intense elevation of both receptors in patients with TBI. These findings are suggestive of an imbalance of the proinflammatory and anti-inflammatory reactions of the central nervous system after trauma, with an emphasis on the proinflammatory mechanisms and a slow increase of potentially anti-inflammatory mediators such as the soluble TNFRs after TBI.

Adolescent↗

Diffusing capacity dependent on lung volume and age in normal subjects.

In this study we determined reference values of total diffusing capacity of carbon monoxide (DLCO) and DLCO per liter alveolar volume (DLCO/VA) at total lung capacity (TLC) and at lung volumes below TLC in sitting position. In 55 healthy nonsmoking volunteers (20-85 yr old), we determined reference values at TLC level in which age was the only parameter. In a subgroup (n = 16) these references did not change by correction for normal variability in hemoglobin concentration. In all volunteers DLCO decreased and DLCO/VA increased with decreasing VA. The increase in DLCO/VA was linear and less in older subjects. We derived equations to calculate reference values of DLCO/VA for lung volumes at and below TLC with two methods: 1) "random coefficients linear" model, which calculates the reference values directly, and 2) a conversion method, which calculates DLCO/VA for lower VA levels from reference values at TLC. An advantage of the conversion method is the suitability of DLCO/VA reference values at TLC of other populations. A disadvantage is the greater standard deviation of these reference values compared with those obtained by the random coefficients linear method. DLCO can be found by multiplying DLCO/VA with VA.

Adult↗

Korean analytical quality assurance (KAQUA) program for biological monitoring.

The Korean analytical quality assurance (KAQUA) program on biological monitoring was performed by the Industrial Health Research Institute in Korea in spring, 1995. The object of the KAQUA program is to improve the analysis capability for the biological monitoring of hazardous chemicals and to confirm the reliability of data from each laboratory. The items chosen for the first round were analyses of lead in blood (PbB) and of hippuric acid in urine (HAU). Eighty-eight laboratories in Korea participated in this program. Two levels of samples, randomly chosen among six levels for each item, were sent to the participants. The consensus value from participants and reference laboratories was determined by statistical analysis and used as a reference value. The tolerance range was +/-15% (+/-6 micrograms/dl for PbB below 40 micrograms/dl) of the reference value. The mean proficiency rate of analytical data increased dramatically in the first round compared with a pre-round that was provided as part of a training course for participants before performing the first round. The mean proficiency rate of PbB was 69% at pre-round and increased at 91% at the first round; for HAU the increase was from 58% to 88%. Not only the analytical results but also raw data were reviewed to find problems which might have arisen during the analytical process. Re-education courses provided after final evaluation of each participant by means of telephone discussion, correspondence course, and experimental practice, were helpful in achieving the purpose of the analytical quality assurance program.

Chemistry, Clinical↗

Isometric strength of the cervical flexor, extensor, and rotator muscles in 220 healthy females aged 20 to 59 years.

STUDY DESIGN: Cross-sectional descriptive study. OBJECTIVES: To determine the maximal isometric strength of the flexor, extensor, and rotator muscles of the cervical spine in healthy females of working age to document reference values for diagnostic and rehabilitation purposes. BACKGROUND: Reference values for the isometric strength of the cervical muscles have often been based on small samples. To date, reference values for rotator muscles of the cervical spine have not been published. METHODS AND MEASURES: The group consisted of 220 volunteer healthy females in 4 age groups (20-29 years, n = 57; 30-39 years, n = 51; 40-49 years, n = 51; 50-59 years, n = 61) from Jyadskyla, Finland. Isometric cervical muscle strength in flexion, extension, and rotation was evaluated with a specially designed measurement system. RESULTS: Across all age groups, mean (+/-SD) maximal isometric neck strength was 73.8 +/- 20.0 N in flexion and 190.8 +/- 31.3 N in extension. Mean (+/-SD) rotation strength was 8.1 +/- 2.3 Nm to the right and 7.9 +/- 2.3 Nm to the left. Absolute strength values did not differ among the age groups. A weak but significant correlation between body mass and neck flexion (r = 0.31, P<.01) and extension (r = 0.25, P<.01) strength was found. Intratester reliability varied from 0.87 to 0.96. CONCLUSIONS: Women aged 20 to 59 years appear to have similar absolute isometric neck muscle strength levels. Thus these values can be used as reference for the working-age female population.

Adult↗

Concentrations of CSF proteins as a measure of blood brain barrier function and synthesis of IgG within the CNS in 'normal' subjects from the age of 6 months to 30 years.

Concentrations of proteins in cerebrospinal fluid (CSF) and serum have been studied in 105 'normal' subjects divided into age groups 0.5-5, 6-15, 16-20, and 21-30 years in order to obtain reference values for information concerning blood brain barrier damage and synthesis of immunoglobulins within the central nervous system (CNS). CSF/serum albumin ratio is superior to CSF total protein as a test of the blood brain barrier function. The IgG synthesis rate per 24 hours and IgG index [CSF/serum IgG ratio]: [CSF/serum albumin ratio] reflect the presence of IgG synthesis within the CNS. The variables reflecting the blood brain barrier function increased with age, the upper values of the CSF/serum albumin ratio being 4.0, 4.9, 6.7 and 6.5 for the mentioned age groups respectively. The upper values for the CSF IgG index remained rather constant in relation to age at 0.62, 0.68, 0.64, and 0.63 respectively. An index value of less than 0.70 and an IgG synthesis of less than 10 mg/24 hours seem to be appropriate upper values as references. Only about 1--2 ml of CSF and 0.5 ml serum are required for the analyses including cell counting and determinations of IgA and IgM index values as well as of glucose and lactate.

Adolescent↗

Peripheral blood reticulocytes and their reference range values for percentage, absolute count, and immature fraction in children, measured with flow cytometry.

Reticulocyte count by manual method has been the assay traditionally used to evaluate the status of erythropoiesis in hematological disorders with disturbances in erythropoietic activity. However, due to its variability, it is rather a semiquantitative method. Automated reticulocyte counting based on flow cytometry has provided more objective and exact measure of reticulocytes. Besides traditional parameters, such as percentage and absolute number of reticulocytes, automatic reticulocyte counters can detect differences in the amounts of cellular RNA present in immature erythrocytes that reflect their maturational stages and evaluate indices of reticulocyte maturation such as RMI, HFR, IRF. These parameters can be used as the earliest signs of marrow engraftment after autologous or allogeneic bone marrow transplantation. Currently there is no strict agreement between various automated methods of reticulocyte evaluation. Additionally, lack of standardization and quality control materials for this assay compels determination of own, interlaboratory ranges of reference values for new proposed parameters. A group of 102 children aged from 3 months to 18 years with normal hematological parameters was examined. Samples of blood stained supravitally with thiazole orange were analyzed in a flow cytometer. Results for percentage, absolute number and immature reticulocyte fraction expressed as a mean +/- 2SD were: 2.00 +/- 1.56%, 88.8 +/- 68.94 x 10(3)/microliter, and 0.22 +/- 0.16, respectively. A poor correlation was found between IRF and other parameters, suggesting its independent role as a marker of erythropoietic activity. Automated reticulocyte counting will probably improve the diagnosis and monitoring of many hematological diseases.

Adolescent↗

[Current problems in determining children's nutritional needs].

Meeting children's nutritional needs is of fundamental importance for their immediate and later health, well-being, and performance. Age-adapted reference values of nutrient intake form the basis for analysis of the current situation and for policy planning, but for many nutrients they cannot be precisely defined due to inadequate scientific data. Therefore, such values are often extrapolated from adult reference values based on age-adapted mean body weight or body surface data, although such extrapolation does not reflect age-related physiological changes. There are considerable differences between various expert recommendations, in part also due to differences in definitions and underlying concepts for deriving reference values. Improvements and international harmonization are urgently needed. Nutritional needs of many children and adolescents are not adequately met at present. A particularly obvious indication is the epidemic-like increase of pediatric overweight and obesity, which could result in markedly increased prevalences of later metabolic syndrome, diabetes, and cardiovascular diseases. Contributing to increasing childhood obesity are low physical activity, changing eating culture and behavior, frequent consumption of high-fat foods with high energy density, and increasing portion sizes. Changes are urgently needed and might be achievable with close collaboration between scientists, public institutions, and industry.

Adolescent↗

Determination of lymphocyte immunophenotypic values for normal full-term cord blood.

Normal reference values for flow cytometric immunophenotypic lymphocyte markers for cord blood (CB) were determined using sufficient numbers of subjects for clinical laboratory use. Samples from 202 normal gestations were processed by whole blood lysis and analyzed in the following combinations: CD14/45, CD4/3, CD8/3, CD45RA/4, CD29/4, CD56/3, Cd19/3, CD19/10. Thirty-five adult laboratory volunteers were analyzed as controls. When compared to adults, CB showed increased relative percentages of naive T-helper cells, B cells, immature B cells, and CD8+3-cells and decreased T cells, cytotoxic T cells, activated T-helper cells, and large granular lymphocytes (CD56+3+). Significant differences were also found when CB samples were stratified by sex and race. These results provide clinical laboratory normal reference values for lymphocyte markers for CB, demonstrate the need for determining separate standard reference values for significantly different patient populations, provide the basis for future investigation of pathologic gestations and for clinical laboratory applications, and provide insight into early immunologic development.

Adolescent↗

Reference change values and power functions.

Repeated samplings and measurements in the monitoring of patients to look for changes are common clinical problems. The "reference change value", calculated as zp x [2 x (CVI2 + CVA2)](1/2), where zp is the z-statistic and CVI and CVA are within-subject and analytical coefficients of variation, respectively, has been used to detect whether a measured difference between measurements is statistically significant. However, a reference change value only detects the probability of false-positives (type I error), and for this reason, a model to calculate the risk of missing significant changes in serial results from individuals (probability of false-negatives) is investigated in this work by means of power functions. Therefore, when an analyte is being monitored in a patient, power functions estimate the probability of detecting a defined real change by measuring the difference. Thus, when a measured difference is the same as the calculated reference change value, then it will be detected in only 50% of situations.

Analysis of Variance↗