Adult Reference Intervals Research Articles

Twenty-four-hour urinary trace element excretion: reference intervals and interpretive issues

Introduction of inductively coupled plasma mass spectrometry (ICP-MS) into clinical laboratories has led to an increasing application of analyses to risk assessment for toxicity from environmental exposure to trace elements, and in occupational monitoring. Interpretation of results from random urine samples may be problematic and measurement of excretion over 24 h is sometimes preferable. Recent reference data are sparse. Twenty-four-hour urine samples from 111 healthy adults from the renal stones clinic in Southampton, UK, were analysed for 31 trace elements using ICP-MS and for zinc using atomic absorption spectroscopy. Non-parametric 0.95 coverage intervals were determined for trace element excretion per 24 h and as a ratio to creatinine, for the full study cohort and separately for men (n=77) and women (n=34). Beryllium was undetectable in 95% of samples, bismuth in 87% and uranium in 75%. In comparison with published ranges, reference intervals for this cohort were higher for molybdenum, tin and vanadium, and for arsenic due to inclusion of fish arsenicals. Aluminium, chromium, iron, lead and mercury were lower. In our cohort, 24-h excretion of 17 elements was significantly higher in men than in women. However, when expressed as trace element to creatinine ratios, the situation reversed strikingly. Because of their lower creatinine excretion, ratios for 18 elements were significantly higher for women. New adult reference intervals were obtained for 24-h urine trace element excretion. Trace element:creatinine ratios must be used cautiously, with separate ranges for men and women.

Laboratory values in a Spanish population of older adults: A comparison with reference values from younger adults

ObjectiveTo examine the laboratory indices in a population aged 65 years or more and compare them with the reference values used for young adults. Study designDistribution patterns of frequently used biochemical and hematological indices were examined in a sample (N=600) of non-institutionalized adults aged over 65. Outcome measuresThe obtained values were compared with the reference intervals for young adults. ResultsOn some of the indices analyzed, large proportions of the participants had values above the upper limit of the reference interval: glucose, 25.0%; urea, 26.6%; creatinine, 27.2% of males; total cholesterol, 54.6%; and low-density lipoprotein cholesterol, 35.8%. Of the participants who met the World Health Organization's diagnostic criteria for diabetes, 31.8% said they had not been previously diagnosed. Similarly, 74.9% of subjects with total cholesterol values above the reference value indicated in the European guidelines on cardiovascular disease said they had not been diagnosed with dyslipidemia, as did 75.5% of those with low-density lipoprotein cholesterol values above the European reference value. The proportion of participants who were not aware that they might be suffering from those disorders was significantly higher among those who reported not having visited their doctor within the last 6 months. ConclusionFurther studies should examine whether the use of adapted, more appropriate reference values for elderly populations will help physicians to make early and correct diagnoses and to decide when medical intervention is required.

A Liquid Chromatography–Tandem Mass Spectrometry Method for Salivary Testosterone with Adult Male Reference Interval Determination

To the Editor: Our laboratory has extensive experience in developing liquid chromatography–tandem mass spectrometry (LC-MS/MS)1 methods for routine use in the clinical laboratory. We previously developed an LC-MS/MS assay for serum testosterone and androstenedione (1). In collaboration with the National Survey of Sexual Attitudes and Lifestyles (NATSAL) working group, we have now developed an LC-MS/MS assay for salivary testosterone (Sal-T). Sal-T is a filtrate of plasma containing only the free fraction. Free testosterone (FT) is considered the physiologically active form and more accurately reflects androgen exposure in target tissues than serum total testosterone. Methods to measure serum FT are unsuitable for the routine clinical laboratory, and the reliability of mathematical algorithms to derive serum FT are questionable, with no consensus. Direct measurement of Sal-T therefore offers a potentially more accurate and convenient alternative to measuring serum FT, particularly in conditions affecting sex hormone–binding globulin. Our method used samples collected via an unstimulated passive-drool technique. Volunteers rinsed their mouth with water, refrained from eating, and did not brush their teeth 30 min before sampling. Samples were collected by drooling down a plastic straw into a collection vial; the saliva sample was then frozen at −80 °C. Samples were thawed, mixed, and centrifuged; the clear supernatant was then used for analysis. Sample preparation involved …

Free cortisol method comparison: Ultrafiltation, equilibrium dialysis, tracer dilution, tandem mass spectrometry and calculated free cortisol

BackgroundFree cortisol (FC) can be calculated from measurements of total cortisol and binding proteins or measured after mechanical separation of unbound and bound fractions by equilibrium dialysis or ultrafiltration. FC can then be measured indirectly by 3H-cortisol dilution or directly by immunologic or tandem mass spectrometry assays. MethodsWe compared FC measured with ultra high performance liquid chromatography – tandem mass spectrometry (UHPLC MS/MS) with 3H-cortisol dilution in ultrafiltrates and dialysates and also with calculated FC (Coolens equation). An adult FC reference interval was established. ResultsThe UHPLC MS/MS and 3H-cortisol dilution methods were non-linearly related (Cusum linearity test p<0.001) but well correlated (R2=0.984). FC calculated with Coolens equation agreed with the UHPLC MS/MS method. Impurity of 3H-cortisol and non-specific adsorption were excluded as causes on non-linearity. Ultrafiltration was linearly related to equilibrium dialysis, simpler to perform and more repeatable. A gender non-specific FC reference interval of 2.1–19.1nmol/L was established. ConclusionsIn view of the non-linearity between measuring techniques and the variability of reported reference ranges, care should be exercised in adopting a reference range. The ultrafiltration UHPLC MS/MS method we described is robust and suitable for use in a routine laboratory.

Serum steroid profiling by isotopic dilution-liquid chromatography–mass spectrometry: Comparison with current immunoassays and reference intervals in healthy adults

Background The simultaneous, rapid and reliable measurement of a wide steroid panel is a powerful tool to unravel physiological and pathological hormone status. Clinical laboratories are currently dominated by high-throughput immunoassays, but these methods lack specificity due to cross-reactivity and matrix interferences. We developed and validated an isotopic dilution-liquid chromatography–tandem mass spectrometry (ID-LC–MS/MS) method for the simultaneous measurement of cortisol, corticosterone, 11deoxycortisol, androstenedione, deoxycorticosterone (DOC), testosterone, 17OHprogesterone, dehydroepiandrosterone (DHEA) and progesterone in serum, and compared it to routine immunoassays employed in our laboratory. We also established adult reference intervals in 416 healthy subjects. Methods 0.9 ml of serum were spiked with labelled internal standards (IS) and extracted on C18 cartridges. Eluate was injected into a two-dimensional LC-system, purified in a perfusion column and separated on a C8 column during a 21 min gradient run. Analytes were revealed by atmospheric pressure chemical ionization (APCI) followed by multiple reaction monitoring (MRM) analysis. Results Of the four immunoassays compared with the ID-LC–MS/MS method, only the results of ElecsysE170 for cortisol, testosterone in males and progesterone > 1 ng/ml were in agreement with ID-LC–MS/MS. ElecsysE170 for testosterone in females and progesterone < 1 ng/ml, Immulite2000 for androstenedione, DSL-9000 for DHEA and 17OHP Bridge for 17OHprogesterone, respectively, showed poor agreement. Reference intervals and steroid age and fertility related fluctuations were established. Conclusion Our ID-LC–MS/MS method proved to be reliable and sensitive in revealing steroid circulating concentrations in adults and in highlighting the limits of routine immunoassays at low concentrations.

Liquid Chromatography–Tandem Mass Spectrometry Assay for Androstenedione, Dehydroepiandrosterone, and Testosterone with Pediatric and Adult Reference Intervals

Measurement of serum androgens is important in adult, geriatric, pediatric endocrinology, and oncology patients. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous measurement of androstenedione, dehydroepiandrosterone (DHEA), and testosterone in these patients. We spiked 200 muL of serum or plasma with isotope-labeled internal standards and performed extraction with methyl t-butyl ether. We then derivatized the extracts with hydroxylamine and analyzed them by LC-MS/MS using a 2-dimensional chromatographic separation with a 3.5-min analysis time. Total imprecision for each analyte was <11.2%. Limits of quantification were 10, 50, and 10 ng/L for androstenedione, DHEA, and testosterone, respectively. Reference intervals were established for children (age 6 months to 17 years), men, and women. Androstenedione and DHEA concentrations were lowest in 2- to 3-year-old children. Adult concentrations were achieved in girls at Tanner stage 3 and in boys at Tanner stage 4-5. In premenopausal and (postmenopausal) women the median concentrations of androstenedione, DHEA, and testosterone were 810 (360), 3000 (1670), 270 (180) ng/L, respectively. In postmenopausal women, concentrations of testosterone were age independent, whereas androstenedione and DHEA concentrations decreased with age. In men the median concentrations of androstenedione, DHEA, and testosterone were 440, 2000, and 3700 ng/L, respectively. In men older than 40 years, median concentrations decreased at rates of 5%, 10%, and 20% per decade for androstenedione, DHEA, and testosterone, respectively. This LC-MS/MS method has the required lower limit of quantification and specificity for analysis of endogenous concentrations of androgens in all groups studied. Reference intervals were established for healthy children and adults.

Thyroid hormone reference intervals and the prevalence of thyroid antibodies

To establish new reference intervals for thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) on the Beckman Coulter DxI 800 in healthy Turkish adults and assess the prevalence of laboratory evidence of thyroid antibodies in this population. Materials and methods: Specimens were obtained from 619 healthy volunteers (338 females, 281 males).The study was conducted with health care professionals and their relatives, The mean age of all the subjects was 34.7 and the median was 31 years, with ages ranging from 15 to 84. Moreover, the subjects had no evidence of thyroid autoimmunity or a history of drug use, both of which might interfere with thyroid function. Results: After exclusion of samples positive for thyroid antibodies (Antithyroperoxidase; TPOAb, Antithyroglobulin; TgAb), the final sample size for the evaluation of TSH, FT3, and FT4 reference ranges was 509 (254 females, 255 males) and the age range was 15-80 (mean 34.1, median 30). The prevalence of antithyroid antibodies was 17.8% in total and positive thyroid antibodies were more common among females (13.6%) than males (4.2%). We established the reference intervals for the healthy adults as 0.41-4.25 mIU/L for TSH, 0.61-1.06 ng/dL (7.85-13.64 pmol/L) for FT4, and 2.62-3.84 pg/mL (4.02-5.90 pmol/L) for FT3. Conclusion: The reference intervals of thyroid hormones vary considerably from those of other populations and the intervals recommended by the manufacturer. This underlines the need for population-specific reference ranges.

Analytical validation of serum bone alkaline phosphatase (BAP OSTASE) on Liaison

The goal of this study was to validate the DiaSorin Liaison BAP OSTASE, a new method for measurement of bone alkaline phosphatase (BAP), and to compare this method with the Beckman-Coulter Access Ostase. We also wanted to establish the reference range for BAP in adults and children. We determined the precision, functional sensitivity, recovery, linearity and measurement uncertainty, accuracy profile and beta-expectation limits. We defined an adult reference interval using individuals with 25-OH vitamin D >80 nmol/L, parathormone <58 ng/L, and normal calcium, phosphorous and estimated glomerular filtration rate. Each adult subclass (men/non-menopausal women/menopause women) contained 120 individuals. We also determined the 2.5th and 97.5th percentiles from a population of 450 children, stratified according to age and gender. The results of the validation showed: precision <6%, functional sensitivity <0.74 microg/L, mean recovery 98.8+/-4.2% and good linearity. Relative uncertainty ranged from 9.0% to 12.9%, and the risk of one result falling out of the +/-15% acceptance limits was <5% for concentrations between 7 and 94 microg/L. The Bland-Altman plot showed no systematic bias between the two methods. In adults, we did not find any statistical difference between the different subclasses. The upper limit of normality observed in the entire population (n=360) was 21.3 microg/L (90% CI: 18.3-24.2 microg/L). The Liaison BAP OSTASE is a robust method, and is completely validated between 7 and 93 microg/L: in this range, 95% of the values obtained will be within +/-15% of the true value.

CLSI-derived hematology and biochemistry reference intervals for healthy adults in eastern and southern Africa.

BackgroundClinical laboratory reference intervals have not been established in many African countries, and non-local intervals are commonly used in clinical trials to screen and monitor adverse events (AEs) among African participants. Using laboratory reference intervals derived from other populations excludes potential trial volunteers in Africa and makes AE assessment challenging. The objective of this study was to establish clinical laboratory reference intervals for 25 hematology, immunology and biochemistry values among healthy African adults typical of those who might join a clinical trial.Methods and FindingsEqual proportions of men and women were invited to participate in a cross sectional study at seven clinical centers (Kigali, Rwanda; Masaka and Entebbe, Uganda; two in Nairobi and one in Kilifi, Kenya; and Lusaka, Zambia). All laboratories used hematology, immunology and biochemistry analyzers validated by an independent clinical laboratory. Clinical and Laboratory Standards Institute guidelines were followed to create study consensus intervals. For comparison, AE grading criteria published by the U.S. National Institute of Allergy and Infectious Diseases Division of AIDS (DAIDS) and other U.S. reference intervals were used. 2,990 potential volunteers were screened, and 2,105 (1,083 men and 1,022 women) were included in the analysis. While some significant gender and regional differences were observed, creating consensus African study intervals from the complete data was possible for 18 of the 25 analytes. Compared to reference intervals from the U.S., we found lower hematocrit and hemoglobin levels, particularly among women, lower white blood cell and neutrophil counts, and lower amylase. Both genders had elevated eosinophil counts, immunoglobulin G, total and direct bilirubin, lactate dehydrogenase and creatine phosphokinase, the latter being more pronounced among women. When graded against U.S.-derived DAIDS AE grading criteria, we observed 774 (35.3%) volunteers with grade one or higher results; 314 (14.9%) had elevated total bilirubin, and 201 (9.6%) had low neutrophil counts. These otherwise healthy volunteers would be excluded or would require special exemption to participate in many clinical trials.ConclusionsTo accelerate clinical trials in Africa, and to improve their scientific validity, locally appropriate reference ranges should be used. This study provides ranges that will inform inclusion criteria and evaluation of adverse events for studies in these regions of Africa.

Serum β2-microglobulin measured by immunonephelometry: expression patterns and reference intervals in healthy adults

Serum beta2-microglobulin (beta2m) has been established as a marker of disease activity in malignancies, autoimmune conditions and infections. Despite its important role in prognosis assessment and disease monitoring, relatively few studies are available on its expression in healthy individuals. Furthermore, interpretation of results is hampered by the variety in reference limits due to differences in methodology, sample population and statistics. Serum beta2m concentrations were measured using a microparticle-enhanced immunonephelometric method in 183 healthy blood donors aged 29-75 years. The median beta2m concentration was 1.67 (0.88-2.75) mg/L with no difference between men and women (1.71 mg/L vs. 1.62 mg/L, p<0.07). A linear correlation was found between beta2m and age (p<0.0001), serum concentrations significantly higher in older subjects (1.55, 1.59, 1.70, and 1.87 mg/L in age groups of 29-40, 40-50, 50-60 and 60-75 years, respectively, p<0.0001). Reference intervals obtained by non-parametric estimation after partitioning by age were 1.02-2.46 mg/L vs. 1.29-2.70 mg/L in younger (29-49 years) vs. older (50-75 years) individuals. These data can help standardise beta2m reference limits and support age-adjusted comparisons in clinical studies.

Adult reference intervals of general chemistries in Hong Kong Chinese

Aim The importance of establishing reliable reference intervals for local populations cannot be overemphasised. The reference intervals of analytes obtained from literature and manufacturers may not apply to our serving population due to differences in subject ethnicity and assay principle. The objective of this study was to set up reference intervals of common serum analytes for local Hong Kong Chinese. Methods Healthy local Chinese blood donors were recruited and blood specimens were obtained after questionnaire screening and consent. Samples were processed and analysed by Beckman Coulter UniCel Chemistry Analyzers. Reference limits were subsequently defined by statistical methods. Results Data from 803 subjects were analysed. The reference intervals of 21 analytes were generally similar to those provided by the assay manufacturer. However, we found higher upper reference limits for creatine kinase and lower potassium reference limits in our group, which might be due to genuine ethnic difference, lifestyle and blood collection procedure variations. Conclusion Reference intervals of common serum analytes have been set up for the local Chinese population. Some of them are not in accordance with those documented in the literature or Manufacturer’s Insert. Clinicians can make use of our results for quality patient care and management in our population.

Pediatric reference intervals for thyroid hormone levels from birth to adulthood: a retrospective study

BackgroundAge- and sex-specific reference intervals are an important prerequisite for interpreting thyroid hormone measurements in children. However, only few studies have reported age- and sex-specific pediatric reference values for TSHbasal (TSH), free T3 (fT3), and free T4 (fT4) so far. Reference intervals are known to be method- and population-dependent. The aim of our study was to establish reference intervals for serum TSH, fT3, and fT4 from birth to 18 years and to assess sex differences.Methods2,194 thyroid hormone tests obtained from a hospital-based pediatric population were included into our retrospective analysis. Individuals with diagnoses or medications likely to affect thyroid function were primarily excluded, as well as the diagnostic groups, if different from the purely healthy subgroup (n = 414). Age groups were ranging from 1 day to 1 month, 1 – 12 months, and 1 – 5, 6 – 10, 11 – 14, and 15 – 18 years, respectively. Levels of fT3, fT4 and TSH were measured on Advia® Centaur™ automated immunoassay system.ResultsThe final sample size for reference data creation was 1,209 for TSH, 1,395 for fT3, and 1,229 for fT4. Median and 2.5/10/25/75/90/97.5 percentiles were calculated for each age group. Males had greater mean fT3 concentrations than females (p < 0.001). No sex-differences were found for TSH and fT4 between age-matched serum samples. Median concentrations of fT3, fT4 and TSH were greatest during the first month of life, followed by a continuous decline with age.ConclusionOur results corroborate those of previous studies showing that thyroid hormone levels change markedly during childhood, and that adult reference intervals are not universally applicable to children. Moreover, differences of our reference intervals compared to previous studies were observed, likely caused by different antibody characteristics of various analytical methods, different populations or undefined geographic covariates, e.g. iodine and selenium status.

Automated HPLC Assay for Urinary Collagen Cross-links: Effect of Age, Menopause, and Metabolic Bone Diseases

The pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are established markers of bone resorption. We evaluated the analytical and clinical performance of a commercially available PYD HPLC assay and established reference intervals in children and adults. We used a commercially available reagent set (Chromsystems Instruments & Chemicals) to measure PYD and DPD in 319 healthy controls (156 premenopausal women, 80 healthy men, and 83 healthy children age 1 month to 14 years) and 397 patients with metabolic bone diseases (postmenopausal osteoporosis, n = 175; male osteoporosis, n = 176; hyperparathyroidism, n = 17; hyperthyroidism, n = 19; Paget disease, n = 10). The mean intraassay and interassay CVs were <6% and <8% for both PYD and DPD, respectively. The reference interval was constant for premenopausal women in the age group 20-49 years. In men, cross-link values peaked at 20-29 years and decreased thereafter. Women with postmenopausal osteoporosis had significantly higher PYD (51%) and DPD (58%) values compared to premenopausal women. Similar results were found in osteoporotic men. In children the highest values were found in the first weeks and months after birth, followed by a decrease of 50%-60% at age 11-14 years. In metabolic bone diseases cross-link concentrations were significantly increased. The DPD:PYD ratio (mean value approximately 0.2) was remarkably constant in all populations evaluated. The automated HPLC assay is a precise and convenient method for PYD and DPD measurement. We established reference intervals for adult women and men and for children up to 14 years old. The cross-link concentrations we determined by use of this HPLC method confirm its clinical value in enabling identification of increased bone resorption in patients with metabolic bone diseases.

Analysis of urinary aromatic acids by liquid chromatography tandem mass spectrometry

The separation and detection of 11 urinary aromatic acids was developed using HPLC-MS/MS. The method features a simple sample preparation involving a single-step dilution with internal standard and a rapid 8 min chromatographic separation. The accuracy was evaluated by the recovery of known spikes between 87 and 110%. Inter- and intra-assay precision (CV) was below 11% in all cases and the analytes were observed to be stable for up to 8 weeks when stored at -20 degrees C. The method was validated based upon linearity, accuracy, precision and stability and was used to establish reference intervals for children and adults.

Normal thrombin generation in neonates in spite of prolonged conventional coagulation tests

Conventional coagulation tests might be inadequate to explore mechanisms regulating thrombin generation in neonates, because they do not allow full activation of the reduced levels of protein C. Therefore, they do not reflect the action of pro- and anti-coagulants as does the endogenous thrombin potential assessed in the presence of thrombomodulin. Endogenous thrombin potential measured without thrombomodulin was greater than the lower-limit of the adult reference interval in 30% of 109 full-term and 49% of 55 pre-term neonates, a finding consistent with the reduced levels of procoagulants in this setting. When the test was modified adding thrombomodulin, endogenous thrombin potential reverted into the adult reference interval in 97% and 100% full-term and pre-term neonates. In conclusion, the coagulation balance in neonates is restored by the concomitant reduction of pro- and anticoagulants. The restored balance can be shown in vitro by the endogenous thrombin potential test that includes thrombomodulin, but not by conventional coagulation tests.

Free Thyroid Hormones in Serum by Direct Equilibrium Dialysis and Online Solid-Phase Extraction–Liquid Chromatography/Tandem Mass Spectrometry

Measurements of free thyroxine (FT4) and free triiodothyronine (FT3) are important for the diagnosis and monitoring of thyroid diseases. Considerable differences among methods limit their clinical utility, however, and accurate methods are needed for various clinical specimens. We describe a direct equilibrium dialysis (ED)-liquid chromatography (LC)/tandem mass spectrometry (MS/MS) method for FT4 and FT3. ED was selected as the separation step. Serum samples were dialyzed 1:1 against a simple protein-free buffer for 20 h at 37 degrees C. Thyroid hormones in dialysates were purified by online solid-phase extraction (SPE), then chromatographically separated and quantified in positive ion and multiple reaction monitoring modes. For FT4 and FT3, the lower and upper limits of quantification were 1 ng/L (pg/mL) and 400 ng/L with total imprecision <10%. The method correlated well with an ED-RIA, 2 direct immunoassay methods for FT4, and 1 direct immunoassay and 1 tracer dialysis method for FT3. The adult reference intervals were 12.8-22.2 ng/L for FT4 and 3.62-6.75 ng/L for FT3. Reference intervals for the second trimester of pregnancy (14-20 weeks of gestation) were also established. We developed a simple protein-free buffer and ED procedure. The performance characteristics and high throughput of the LC-MS/MS method with online SPE for FT4 and FT3 (also reverse T3) are sufficient for the intended clinical use.

Reference Intervals for Serum Creatinine Concentrations: Assessment of Available Data for Global Application

Reference intervals for serum creatinine remain relevant despite the current emphasis on the use of the estimated glomerular filtration rate for assessing renal function. Many studies on creatinine reference values have been published in the last 20 years. Using criteria derived from published IFCC documents, we sought to identify universally applicable reference intervals for creatinine via a systematic review of the literature. Studies were selected for inclusion in the systematic review only if the following criteria were met: (a) reference individuals were selected using an "a priori" selection scheme, (b) preanalytical conditions were adequately described; (c) traceability of the produced results to the isotope dilution-mass spectrometry (IDMS) reference method was demonstrated experimentally, and (d) the collected data received adequate statistical treatment. Of 37 reports dealing specifically with serum creatinine reference values, only 1 report with pediatric data and 5 reports with adult data met these criteria. The primary reason for exclusion of most papers was an inadequate demonstration of measurement traceability. Based on the data of the selected studies, we have collated recommended reference intervals for white adults and children. Laboratories using methods producing traceable results to IDMS can apply the selected reference intervals for serum creatinine in evaluating white individuals.

Normal blood cells reference intervals of healthy adults at the Gaza Strip—Palestine

Hematological parameters are affected by different factors that include age, sex, smoking, ethnicity, and environmental altitude. It has been justified that each population must establish its own normal reference intervals to be used in clinical assessments and interpretations. Hematological reference intervals for adults from the Gaza Strip-Palestine have never been addressed. Therefore, this study was designed and aimed at the establishment of normal blood cells reference intervals for healthy adults at the Gaza Strip-Palestine. This study involved 89,491 apparently healthy individuals (from both sexes and from the different governorates of the Gaza Strip) who were referred to the Thalassemia Central Laboratory during the period from September 2000 until February 2008. Complete blood counts were performed. Subjects were categorized into subgroups according to gender, smoking habit, and age (15-18, 19-45, and >45 years old). For each subgroup, descriptive and comparative statistical analysis was performed for hematological parameters. The results showed substantial differences between males and females, between smokers and nonsmokers, and between the different age groups. Moreover, reference intervals derived from our population are markedly shifted downward as compared with Western European and American populations. It was concluded that separate and region-specific reference intervals based on gender, smoking, and age for the Palestinian population at the Gaza Strip should be generalized for clinical laboratories and clinical practitioners, which could help in interpreting laboratory hematological tests more specifically, and potentially develop the quality of medical care provided to patients.

Hematologic values in young pretraining healthy Greyhounds

Greyhound dogs have numerous clinicopathologic differences compared with other dog breeds, most notably in their hematologic profiles. The hematologic differences are likely related to breed; however, the influence of other factors, including age, sex, and training, has not been fully determined. The aim of this study was to assess hematologic values in young, healthy, pretraining Greyhounds and to determine the effects of age and sex on these findings. Jugular venous EDTA-anticoagulated blood samples were collected from 43 healthy, pretraining Greyhounds between 5 and 13 months of age. Samples were analyzed within 24 hours of collection on an Abbott CELL-DYN 3500R hematology analyzer. Mean hematologic results for different age groups, and correlation with age and sex were determined for each analyte. Results were compared with adult canine, nonbreed-specific reference intervals. From the age of 9 to 10 months, Greyhounds had higher HCT, hemoglobin concentration, and RBC counts compared with adult canine reference intervals. Younger Greyhounds (5-6 months) had values comparable with reference intervals. Mean total WBC, neutrophil, lymphocyte, and platelet counts tended to be toward the lower end or below the reference intervals. HCT, hemoglobin concentration, and RBC counts were correlated positively with age, and platelet count was correlated negatively with age. No differences were found based on sex. These results confirm that significant hematologic differences exist in pretraining Greyhounds by 9 to 10 months of age, when compared with adult canine, nonbreed-specific reference intervals; however, these differences are less marked in Greyhounds 5 to 6 months old. Given these findings, it is unlikely that factors such as training or racing are responsible for differences in hematologic values between adult Greyhounds and other breeds.

The origin of reference intervals : A college of american pathologists Q-probes study of normal ranges used in 163 clinical laboratories

•Context.-Standards have been developed for establishing reference intervals, but little is known about how intervals are determined in practice, interlaboratory variation in intervals, or errors that occur while setting reference intervals. Objectives.-To determine (1) methods used by clinical laboratories to establish reference intervals for 7 common analytes, (2) variation in intervals, and (3) factors that contribute to establishment of intervals. Design.-One hundred sixty-three clinical laboratories provided information about their reference intervals for potassium, calcium, magnesium, thyroid-stimulating hormone, hemoglobin, platelet count, and activated partial thromboplastin time. Results.-Approximately half the laboratories reported conducting an internal study of healthy individuals to validate reference intervals for adults. Most laboratories relied on external sources to establish reference intervals for pediatric patients. There was slight variation in intervals used by the central 80% of study laboratories, but some laboratories outside the central 80% had surprisingly and high limits for their reference intervals. In some cases the intervals used by 2 laboratories had no overlap. For example, one laboratory considered a hemoglobin of 13.8 g/dL in a woman to be low while another considered the same value to be high. Three percent of reference intervals contained a limit that qualified as an using standard statistical tests; we could not identify any practice associated with adoption of outlier intervals. Conclusions.-Many laboratories adopt reference intervals from manufacturers without on-site testing of healthy individuals. Reference intervals used by facilities that forgo on-site testing are not statistically different from intervals validated with on-site studies.