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The reference change value: a proposal to interpret laboratory reports in serial testing based on biological variation.

BACKGROUND: A proposal to calculate and use the reference change value (RCV) as an objective guide for interpreting the numerical results obtained in clinical laboratory serial testing is introduced in this study. METHODS: A database showing the results of a compilation of 191 publications on biological variation and including information on a number of analytes provided the standardized criterion based on biology for calculating the RCVs. RESULTS: For each of the 261 analytes included in the study, the RCV was determined using Harris's formula, replacing analytical imprecision with the desirable specification of analytical quality based on half the within-subject biological variation at 95% probability levels. The result is a guide for a common criterion to identify clinically significant changes in serial results. CONCLUSIONS: The RCV concept is an approach that can be offered by laboratories to assess changes in serial results. The RCV data in this study are presented as a point of departure for a widely applicable objective guide to interpret changes in serial results.

Algorithms↗

Comparison of estimates of zinc absorption in humans by using 4 stable isotopic tracer methods and compartmental analysis.

BACKGROUND: Adjustment of gastrointestinal absorption is the primary means of maintaining zinc homeostasis; however, a precise, accurate method for measuring zinc absorption in humans has not been identified. OBJECTIVE: The purpose of this study was to compare the estimates of the fraction of dietary zinc absorbed (FZA) by using 4 stable isotopic tracer methods: mass balance (MB) corrected for endogenous secretion, fecal monitoring (FM), deconvolution analysis (DA), and the double isotopic tracer ratio (DITR) method. DESIGN: All 4 methods were applied to a single data set for each of 6 women. FZA was also determined for each subject by using a detailed compartmental model of zinc metabolism, and that value was used as the reference with which the simpler methods were compared. RESULTS: The estimates of FZA (&xmacr; +/- SD) determined by DA (0.27 +/- 0. 08) and the DITR technique in plasma (0.30 +/- 0.10), 24-h urine samples (0.29 +/- 0.09), and spot urine samples (0.291 +/- 0.089) all compared well with the FZA reference value from the compartmental model (0.30 +/- 0.10). The MB and FM methods tended to overestimate FZA compared with the reference value. CONCLUSIONS: The determination of FZA by MB or FM is laborious, is sensitive to subject compliance, and may result in an overestimate. DA, although relatively accurate, has the disadvantage of requiring multiple blood drawings over several days. In contrast, the DITR technique applied to a spot urine specimen obtained >/=3 d after tracer administration provides an accurate measure of FZA and is easy to implement; therefore, it is the recommended method for determination of FZA.

Adult↗

Standardization and quantification of radionuclide solid gastric-emptying studies.

UNLABELLED: The purposes of this investigation were to standardize and validate a simple quantitative method for performing radionuclide solid gastric emptying that can be used for any dual-head gamma-camera and to establish reference values. METHODS: After eating a solid meal (egg sandwich) labeled with a radionuclide, 20 healthy volunteers (9 male, 11 female) underwent a 90-min gastric-emptying study performed with a triple-head gamma-camera. Two sets of 3 simultaneous projections were acquired sequentially for 30 s each: anterior, right posterior oblique (RPO), left posterior oblique (LPO), posterior, left anterior oblique (LAO), and right anterior oblique (RAO), and this sequence was repeated continuously for 90 min. Time-activity curves were generated using a gastric region of interest for each of the views as well as the conjugate-view geometric mean (GM) data for the anterior/posterior, LAO/RPO, and RAO/LPO combinations. Quantitative parameters were determined: percentage gastric emptying (%GE) at 90 min, half-time (min) based on an exponential fit, and clearance rate (%/min) based on a linear fit. Reference values were determined on the basis of a 95% confidence interval of the t distribution. The results were statistically analyzed and compared. RESULTS: The %GE reference values were greater for the anterior/posterior GM (>or=33%) than for the LAO (>or=31%) and anterior (>or=30%) GMs. The 3 %GE GM methods, the 3 exponential-fit GM methods, and the 3 linear-fit GM methods had high correlation coefficients (r >or= 0.874), and with only a single exception, there was no statistical difference among them. The LAO method and LAO/RPO GM mean method correlated strongly (r = 0.900) and had similar mean values (52% vs. 51%) and reference values (29% vs. 30%). All 3 methods of GM quantification also correlated strongly, and there was no significant difference among them. CONCLUSION: We have described and validated a simple method for radionuclide solid gastric emptying that can be used with a dual-head gamma-camera. We recommend the anterior/posterior GM method and have established reference values (>or=33%).

Adult↗

Forward leaning reaching task in sitting (FLRS): a new measure for clinical evaluation of hamstring length in children.

BACKGROUND AND PURPOSE: In this study, the rotation of the pelvis was taken into account when assessing the length of hamstrings. A new measure for clinical evaluation was developed to establish reference values of hamstring length in children without movement disabilities for different age groups. Subjects (N = 60) were 3-, 6-, 10- and 14-year-old children (N = 15 for each age group). These values could be helpful in deciding treatment interventions in children with movement disabilities, for example cerebral palsy, when hamstring length is in question. METHOD: The study was performed with subjects sitting and reaching for a touch control on a wall whilst voluntarily rotating the pelvis forwards. By use of digitized video frames, the spatial angles of the lumbar spine and pelvis, as well as the joint angles of hip and knee, were computed at the initial and end positions of a forward leaning reaching task in sitting (FLRS). The active forward leaning induced a forward rotation of the pelvis, causing stretch on the hamstring muscle with extended knee. RESULTS: The results of spatial and joint angle measurements suggest that the difference of the hip joint angle between initial erect and final forward leaned sitting may be used as reference values for hamstring length. Reference values are based on the mean (+/- SE) of means (mean of 15 children, that is, group and individual means of ten trials). CONCLUSIONS: The age group reference values obtained may indirectly give information as to whether the hamstring length of a child with cerebral palsy is within the normative value of age-related control subjects. The new test developed in this study provides a convenient means for measuring hamstring length and could enhance clinical evaluation.

Adolescent↗

[Doppler ultrasound of uterine and fetoplacental circulation: placental laterality, normal values and reference curves].

AIM: Doppler ultrasound assessment of blood flow velocity waveforms from the maternal and fetal sides of the placenta in normal pregnancies, taking into consideration placental location, in order to establish normal values and reference curves. METHOD: A cross sectional study of uneventful singleton pregnancies with gestational ages from 18 to 41 weeks and later on healthy newborns was performed by continuous-wave-Doppler ultrasound. Doppler flow signals from the uterine artery or the corresponding ascending branch and the umbilical arteries were analysed using the resistance index RI. The RI-values from the uterine circulation were classified according to the proximity of the placenta. Normal values and reference curves were established on the basis of centiles. RESULTS: After consideration of exclusion criteria, 757 pregnancies remained for evaluation. The resistance index reference curves of the uterine circulation were dependent on placental location, with proximal RI-values being lower, but with nearly constant course during the second half of pregnancy. In contrast, the umbilical artery RI-values were higher but showed a continuous decrease. CONCLUSION: In the second half of pregnancy, down stream flow resistance of the uterine circulation is very low and nearly constant but depends on placental location. The fetoplacental circulation shows high flow resistances which decrease with increasing gestational age. These reference curves are comparable with others where placental location is taken into consideration.

Adult↗

Serum androgen levels in men: impact of health status and age.

OBJECTIVES: To investigate the impact of health status on androgen levels in men and to assess the age-related changes in androgen levels. METHODS: Sera were obtained from 526 men (age 20 to 89 years) participating in a health screening project and 35 men selected according to the SENIEUR protocol, which excludes those with underlying disease. The health screening project participants were divided into two groups: healthy men (n = 133; group 1) and the remainder (n = 393; group 2). The total testosterone and sex hormone-binding globulin levels were quantified, and the amount of free testosterone (cfT) was calculated. RESULTS: The lowest annual declines in androgen level were observed in group 3 (testosterone 0.2%; cfT 0.4%), followed by group 1 (testosterone 0.4%; cfT 0.8%) and group 2 (testosterone 0.8%; cfT 0.9%). Body mass index and levels of cholesterol, triglycerides, and glucose correlated negatively (P <0.01) with testosterone and cfT. Decade-adjusted reference values (mean +/- 2 standard deviations) for testosterone and cfT were defined. The proposed lower testosterone reference value declined gradually from 3.1 ng/mL (20 to 29 years) to 1.7 ng/mL (70 years or older). CONCLUSIONS: In this cross-sectional study, serum androgens declined in aging men, and the extent of this decrease correlated with health status. A fixed, non-age-adjusted reference value does not adequately reflect this and might lead to a false diagnosis of androgen deficiency, particularly in elderly men. The clinical value of age-related reference values, however, needs to be determined in prospective studies.

Adult↗

Development of criteria for the evaluation of reference method values.

We present a uniform concept for the requirements of reference methods (RMs) used for target-setting in the German external quality assessment (EQA) scheme. It is proposed that the total allowable error (TAE) of the RMs shall be 0.2 times the acceptance limits in the EQA-scheme. From the TAE are derived limits for maximum RM-bias, RM-imprecision, and the number of measurements.

Chemistry, Clinical↗

Delta-aminolevulinic acid dehydratase activity in the general population of southern Minas Gerais, Brazil.

Blood samples were collected from 113 subjects (56 males and 57 females) living in the district of Alfenas, in southern Minas Gerais state, Brazil, to establish reference values for delta-aminolevulinic acid dehydratase activity (ALA-D, EC 4.2.1.24). The state of health of the population was confirmed by hematological and biochemical parameters analyzed in blood and urine samples. ALA-D determination was performed according to the Berlin & Schaller spectrophotometric method. Distribution may be regarded as according to normal distribution and reference values obtained, in micromol x min(-1) x L(-1) erythrocytes, were: mean (+/- SD) = 54.5 (+/- 9.8); 95% confidence interval = 52.7-56.4; lower reference value (mean-2 SD) = 34.9. Mean ALA-D activity was higher than any other published elsewhere and the reference values established are useful as a baseline for evaluating ALA-D activity when monitoring persons exposed to lead. Age, gender, drinking, or smoking did not significantly alter (Student t-test, p < or = 0.05) the reference values for ALA-D.

Adolescent↗

Comparison of closed-vessel and focused open-vessel microwave dissolution for determination of cadmium, copper, lead, and selenium in wheat, wheat products, corn bran, and rice flour by transverse-heated graphite furnace atomic absorption spectrometry.

A method is described for the determination of Pb, Cd, Cu, and Se in cereal samples. An atomic absorption spectrometer equipped with a transverse-heated graphite furnace with Zeeman background correction was used for all determinations. Sample preparation was performed by closed-vessel microwave digestion using nitric acid and focused openvessel microwave digestion using nitric acid-hydrogen peroxide. Both techniques were evaluated by using 15 cereal reference materials and comparing results with certified or reference values for each element. Cereal reference standards obtained from the Community Bureau of Reference (Europe), the National Institute of Standards and Technology (USA), the National Institute for Environmental Studies (Japan), the National Research Centre for Certified Reference Materials (People's Republic of China), and the Canadian Grain Commission were used. Application of a series of t-tests, conducted according to Sidak's modified Bonerroni t-procedure, showed that both techniques yielded accurate results for cereal reference materials. Some differences from certified and reference values, however, were found for each element.

Bread↗

[Bone metabolic markers and diagnosis of abnormal bone and calcium metabolism].

Bone metabolic markers increase in blood or urine, when bone formation or bone resorption accelerates. Reference values of bone metabolic markers are determined in male or female, and in pre- or post-menopause, respectively. Values of bone metabolic markers in most patients with primary osteoporosis were distributed within a reference value, mean+/-1.96 SD. When measured values exceeded a reference values, we should survey a possibility of abnormal calcium or bone metabolism such as primary hyperparathyroidism, renal osteodystrophy, hyperthyroidism and Paget's disease of bone or bone metastasis associated with malignant tumor.

English Abstract↗

Computer-aided anthropometry in the evaluation of dysmorphic children.

OBJECTIVE: Although anthropometry is widely regarded as the technique of choice for the evaluation of dysmorphic features among children, it is only rarely used in clinical practice. Possible reasons for this are the limited access of pediatricians to appropriate reference values and the time-consuming way measurements must be plotted onto growth charts. This article describes a computer program that overcomes these problems and greatly facilitates the use of anthropometric measurements in pediatric medicine. DESIGN: A computer program for PalmOS-based, handheld computers that compares entered anthropometric measurements with age- and gender-matched reference values was developed. The software is distributed free of charge and can be downloaded (www.medgen.unizh.ch/abase/). RESULTS: The ABase software contains age- and gender-matched reference values for 18 anthropometric measures frequently used for the evaluation of dysmorphic children. The proband's age is automatically calculated from the entered birth date and can be corrected for prematurity. Entered measurements are compared with the internal reference values; the results are displayed as percentile ranks or z scores and are plotted on digital growth charts. CONCLUSIONS: The presented software makes anthropometric reference values easily accessible on the ward or in the clinic and greatly reduces the time needed to plot the measurements onto growth charts. This should promote more widespread use of anthropometry in pediatric medicine.

Anthropometry↗

Cardiopulmonary exercise capacity, muscle strength, and physical activity in children and adolescents with achondroplasia.

OBJECTIVE: To study in children with achondroplasia the response to exercise and muscle strength compared with healthy peers and to describe the relation between exercise capacity, anthropometric factors, and physical activity. STUDY DESIGN: Patients (7 boys and 10 girls; mean age, 11.8 +/- 3.3 years) with achondroplasia performed a maximal treadmill exercise test. Anthropometric variables and muscle strength were measured and compared with the general population. The level of everyday physical activity was measured by using a diary. Functional ability was measured by using the Activity Scale for Kids. RESULTS: The exercise capacity of the children with achondroplasia was significantly reduced compared with reference values. All anthropometrical measurements differed significantly from reference values. There was a decrease in muscle strength in almost all muscle groups. We found a reduced physical activity level and impairments in functional ability. CONCLUSIONS: Cardiopulmonary exercise capacity and muscle strength in children with achondroplasia was reduced compared with reference values. Children with achondroplasia have a unique response to exercise. Clinicians should take these characteristic differences into account when the exercise capacity of subjects with achondroplasia is being tested.

Achondroplasia↗

Identification of vertebral deformities in women: comparison of radiological assessment and quantitative morphometry using morphometric radiography and morphometric X-ray absorptiometry.

Our aim was to compare normal vertebral reference values for morphometric radiography (MRX) and morphometric X-ray absorptiometry (MXA) and to compare these methods for the identification of vertebral deformities. We calculated MXA reference values (Hologic QDR 4500 A) for 327 women (ages 22-88 years) randomly selected from local General Practice lists in Sheffield, U.K. MRX reference values were calculated from spinal radiographs for 123 of these subjects (ages 56-88 years). We used these reference values to identify deformities in the MRX and MXA reference populations and in 83 women with osteoporosis (ages 49-87 years). We observed differences in mean deformity of vertebral height ratios measured by MRX and MXA, especially for the mid-to-posterior ratio. We compared agreement between quantitative methods (MRX and MXA) and qualitative radiological assessment. Severity of deformity was defined by semiquantitative (SQ) assessment. Agreement was moderate for MRX (k = 0.59; 95% CI = 0.43-0.77) and for MXA (k = 0.47; 95% CI = 0.29-0.66) in the reference population. Agreement was good for MRX (k = 0.86; 95% CI = 0.82-0.89) and MXA (k = 0.71; 95% CI = 0.66-0.75) in the osteoporotic population. MRX and MXA correctly identified a greater proportion of moderate or severe deformities compared with mild deformities. Sensitivity, specificity, predictive values, and accuracy were slightly better for MRX than for MXA. Although MXA agrees well with qualitative radiological assessment, the large proportion of vertebrae excluded from analysis because of poor image quality limits the diagnostic value of the technique. Reference intervals should be technique specific.

Absorptiometry, Photon↗

Ventilatory and cardiovascular responses to exercise in patients with pectus excavatum.

PURPOSE: Uncertainty exists as to whether pectus excavatum causes true physiologic impairments to exercise performance as opposed to lack of fitness due to reluctance to exercise. The purpose of this study was to examine the effect of pectus excavatum on ventilatory and cardiovascular responses to incremental exercise in physically active patients. METHODS: Twenty-one patients with pectus excavatum (age range, 13 to 50 years; mean [+/- SD] age, 23.6 +/- 8.9 years; severity index range, 3.7 to 8.0; mean severity index, 5.1 +/- 1.2) were referred for preoperative evaluation. Eighteen of the patients (85%) had a history of performing aerobic activity ranging from 30 min to 2 h per day (mean duration, 1.0 +/- 0.61 h per day) for 3 +/- 1.5 days per week. Patients performed pulmonary function tests, and submaximal and maximal incremental exercise testing. RESULTS: On maximal exercise testing, the maximum oxygen uptake (O(2)max), and oxygen-pulse were significantly lower than the reference values (t(20) = 6.17 [p < 0.0001] and t(20) = 4.52 [p < 0.0001], respectively). Furthermore, patients exhibited cardiovascular limitation, but not ventilatory limitation. Despite their high level of habitual exercise activity, the overall metabolic threshold for lactate accumulation was abnormally low (ie, 41% of the reference value for O(2)max) especially in those with a pectus severity index (PSI) of > 4.0 (39% of the reference value of O(2)max), which is consistent with cardiovascular impairment rather than physical deconditioning. Patients with a PSI of > 4.0 were also eight times more likely to have reduced aerobic capacity than patients who had a low severity index, despite their level of exercise participation. On submaximal testing, we found that the time constant for O(2) uptake kinetics was 37.4 s for the on-transit and 41.6 s for the off-transit. The observed values for FVC, FEV(1), maximum voluntary ventilation, and diffusing capacity of the lung for carbon monoxide were significantly lower than reference values, but those for total lung capacity and residual volume were not significantly lower than reference values. CONCLUSIONS: The information derived from this study supports the opinion that pectus excavatum is associated with true physiologic impairment and reduced exercise capacity, predominantly due to impaired cardiovascular performance rather than ventilatory limitation. Furthermore, the impairment is not explained by physical deconditioning.

Adolescent↗

Determinants of heart rate variability.

OBJECTIVES: This study sought to examine clinical determinants of heart rate variability and to report normative reference values for eight heart rate variability measures. BACKGROUND: Although the clinical implications of heart rate variability have been described, clinical determinants and normative values of heart rate variability measures have not been studied systematically in a large community-based population. METHODS: The first 2 h of ambulatory electrocardiographic recordings obtained in Framingham Heart Study subjects attending a routine examination were reprocessed for heart rate variability. Recordings with transient or persistent nonsinus rhythm, premature beats > 10% of total beats, < 1-h recording time or processed time < 50% of recorded time were excluded; subjects receiving antiarrhythmic medications also were excluded. Among five frequency domain and three time domain measures that were obtained, low frequency power (0.04 to 0.15 Hz), high frequency power (0.15 to 0.40 Hz) and the standard deviation of total normal RR intervals based on 2-h recordings were selected for the principal analyses. Variables with potential physiologic effects or possible technical influences on heart rate variability measures were chosen for multiple linear regression analysis. Normative values, derived from a subset of healthy subjects, were adjusted for age and heart rate. RESULTS: There were 2,722 eligible subjects with a mean age (+/-SD) of 55 +/- 14 years. Three separate multiple linear regression analyses revealed that higher heart rate, older age, beta-adrenergic blocking agent use, history of myocardial infarction or congestive heart failure, diuretic use, diastolic blood pressure > or = 90 mm Hg, diabetes mellitus, consumption of three or more cups of coffee per day and smoking were associated with lower values of one or more heart rate variability measures, whereas longer processed time, start time in the morning, frequent supraventricular and ventricular premature beats, female gender and systolic blood pressure > or = 160 mm Hg were associated with higher values. Age and heart rate were the major determinants of all three selected heart rate variability measures (partial R2 values 0.125 to 0.389). Normative reference values for all eight heart rate variability measures are presented. CONCLUSIONS: Age and heart rate must be taken into account when assessing heart rate variability.

Adult↗

[Determination of spirometric values in a normal Chilean population over 5 years old, at sea level].

BACKGROUND: The interpretation of spirometric results requires reference values. Up to the moment, the reference values used in Chile are those of Knudson et al, obtained in a white North American population studied in Tucson, USA. AIM: To obtain reference spirometric values from a Chilean population. SUBJECTS AND METHODS: Maximal expiratory flow-volume curves were obtained from a randomly selected population of 850 healthy non-smoking subjects living at sea level, in cities without atmospheric pollution. Equipment and techniques were used according to the recommendations of the American Thoracic Society. RESULTS: Linear regression equations were obtained, using age and height as independent variables and spirometric values as dependent variables, for both sexes and ages from 6 to 70 years old. Our values for forced vital capacity and forced expiratory volume were 9 to 18% and 10 to 15% higher than those reported by Knudson et al. CONCLUSIONS: Chilean spirometric reference values differ from those used abroad, emphasizing the need to use local standards to interpret spirometric results.

Adolescent↗

The prevalence of gastrointestinal symptoms in patients with chronic renal failure is increased and associated with impaired psychological general well-being.

BACKGROUND: Malnutrition occurs frequently in patients with end-stage renal disease (ESRD). Gastrointestinal (GI) symptoms may lead to reduced food intake, resulting in malnutrition and impaired well-being in these patients. The prevalence of GI symptoms in various chronic renal failure (CRF) groups is unexplored. We assessed the prevalence of GI complaints in patients on either haemodialysis (HD), peritoneal dialysis (PD), or in the pre-dialysis stage. Patients with and without diabetic nephropathy were also compared. METHODS: A total of 233 patients with CRF (128 HD, 55 PD, and 50 pre-dialytic patients) completed two self-administered questionnaires: the Psychological General Well-Being (PGWB) index and the Gastrointestinal Symptom Rating Scale (GSRS), which measures GI symptoms. The values were compared with reference values obtained from the general population. The association between GI symptoms and serum (s-)albumin was also studied. RESULTS: The total GSRS score in patients with CRF was significantly higher than the reference values (HD 2.14 (1.97-2.31), PD 2.24 (2.00-2.48), and pre-dialytic patients 2.03 (1.82-2.25) vs controls 1.53 (1.50-1.55; P<0.001). When comparing CRF subgroups there was no overall difference between the groups, but PD patients had more severe reflux and eating dysfunction. In patients with diabetic nephropathy, only eating dysfunction was significantly more common than in the non-diabetic patients. There was a negative correlation between GI symptoms and psychological general well-being in CRF patients (Rho=-0.46, P<0.001) indicating that patients with a high GI symptom profile have impaired psychological general well-being. A negative correlation was found between eating dysfunction and s-albumin (Rho=-0.33, P<0.01). CONCLUSION: The prevalence of GI symptoms is high in patients with CRF and is associated with impairment in psychological general well-being. Presence of dialysis or not, type of dialysis, and presence or absence of diabetes mellitus seem to have limited impact on GI symptoms.

Attitude to Health↗

Quantitation of flow in the superior sagittal sinus performed with cine phase-contrast MR imaging of healthy and achondroplastic children.

BACKGROUND AND PURPOSE: Cine phase-contrast (PC) MR imaging is a convenient and effective method for measuring volumetric flow rates in vivo. We attempted to evaluate changes in blood flow in the superior sagittal sinus (SSS) in children and to assess the hypothesis that restricted venous outflow attributable to stenosis of the jugular vein causes hydrocephalus in achondroplasia. METHODS: Blood flow in the SSS was measured by using cine PC MR imaging with a 1.5-T scanner. After validation, 35 neurologically healthy children as well as eight children with achondroplasia (five with hydrocephalus) and two children with obstructive hydrocephalus were studied. Average flow velocity over the cardiac cycle and volumetric flow rate in the SSS were obtained. The data for healthy children were plotted as a function of age, and reference values were defined by using a five-point smoothing. RESULTS: In healthy children, flow velocity ranged from 92 to 196 mm/s (mean, 136), and flow rate from 189 to 688 mL/min (mean, 484). The flow rate showed changes statistically related to age. It rapidly increased during the first 2 years and reached a peak by 6 to 8 years of age. The flow velocity showed a similar pattern, but not with significant correlation. In all cases of achondroplasia with hydrocephalus, both flow values were reduced below the reference values minus one standard deviation. In cases of achondroplasia without hydrocephalus, and in obstructive hydrocephalus, the values were not reduced. CONCLUSION: Blood flow in the SSS reflects brain maturation. Hydrocephalus associated with achondroplasia was found to be closely related to reduced flow in the SSS, which supports the hypothesis that restricted venous outflow causes hydrocephalus in cases of achondroplasia.

Achondroplasia↗