'Aussie Normals': an a priori study to develop reference intervals in a healthy Australian population using the Beckman Coulter LH 750 Haematology Analyser as candidates for harmonised values.

Reference limits or intervals are important benchmarks or tools that help the clinician to distinguish between a result that is most likely to lie within a 'healthy' or diseased category. It has been suggested that a review of haematology reference intervals is long overdue. In this study we report on our findings for analytes routinely measured in a complete blood count (CBC) performed on the Beckman Coulter LH 750 analyser and an additional comparative study using the Beckman Coulter LH 750, the Sysmex XN and Abbott Sapphire. The results from the comparative study indicate that bias would not prevent harmonisation of reference intervals for these common haematology parameters. The results offered by the Aussie Normals study represent good candidates as the basis for harmonisation reference intervals.

'Aussie normals': an a priori study to develop clinical chemistry reference intervals in a healthy Australian population.

Development of reference intervals is difficult, time consuming, expensive and beyond the scope of most laboratories. The Aussie Normals study is a direct a priori study to determine reference intervals in healthy Australian adults. All volunteers completed a health and lifestyle questionnaire and exclusion was based on conditions such as pregnancy, diabetes, renal or cardiovascular disease. Up to 91 biochemical analyses were undertaken on a variety of analytical platforms using serum samples collected from 1856 volunteers. We report on our findings for 40 of these analytes and two calculated parameters performed on the Abbott ARCHITECTci8200/ci16200 analysers. Not all samples were analysed for all assays due to volume requirements or assay/instrument availability. Results with elevated interference indices and those deemed unsuitable after clinical evaluation were removed from the database. Reference intervals were partitioned based on the method of Harris and Boyd into three scenarios, combined gender, males and females and age and gender. We have performed a detailed reference interval study on a healthy Australian population considering the effects of sex, age and body mass. These reference intervals may be adapted to other manufacturer's analytical methods using method transference.

Routine exercise alters measures of immunity and the acute phase reaction.

PURPOSE: To expand our understanding of the overall anti-inflammatory nature of routine exercise; we compared resting blood values from adults who habitually undertake frequent, moderate levels of exercise to reference interval values assumed to reflect values largely from non-exercisers. This information would be useful for clinicians interpreting blood tests assessing inflammatory, immune and acute phase responses. METHODS: Blood samples were collected from 119 community adult self-reported routine exercisers (61 males and 58 females aged 18-60 years). Samples were analysed for 20 cellular and non-cellular biomarkers which included 11 immunological and 9 acute phase reactants. These data were compared to reference intervals from the same hospital laboratory that performed the analyses on our participants' samples. Individual analyte values were also compared with participants' self-reported 150 day exercise patterns which included exercise frequency, intensity and duration. RESULTS: In general, mean values for routine exercise participants fell at the lower end of laboratory reference interval for most inflammatory analytes. More than 10 % of participants had numbers of CD19(+), CD8(+) and 16/56(+) NK cells below the low end of the respective reference interval. More than 10 % of observed acute phase reactant values (for C3, haptoglobin and ferritin) were also below the low end of the reference interval. At rest IgM (r = -0.22) and IgG (r = -0.31) values correlated negatively (p < 0.05) with exercise load. CONCLUSIONS: Routine exercise appears to lower resting numbers of a variety of immune cell-types as well as the concentration of several classical acute phase reactants. These wide-ranging systemic effects are presumably adaptive changes, not pathology and collectively confirm the well-reported and clinically important anti-inflammatory effects of exercise.

Effects of probiotic supplementation over 5 months on routine haematology and clinical chemistry measures in healthy active adults.

Use of probiotic-containing foods and probiotic supplements is increasing; however, few studies document safety and tolerability in conjunction with defined clinical end points. This paper reports the effects of 150 days of supplementation with either a single- (Bifidobacterium animalis subsp. lactis Bl-04) or a double-strain (Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis Bi-07) probiotic on routine haematology and clinical chemistry measures in healthy active adults. Pre- to post-intervention changes in laboratory measures were determined and compared between supplement and placebo groups. Overall there were few differences in routine haematology and clinical chemistry measures between supplement and placebo groups post-intervention. Exceptions included plasma calcium (P=0.03) and urea (P=0.015); however, observed changes were small and within assay-specific laboratory reference ranges. These data provide evidence supporting the use of these probiotic supplements over a period of 5 months in healthy active adults without obvious safety or tolerability issues.

High-resolution SNP microarray investigation of copy number variations on chromosome 18 in a control cohort.

Copy number variations (CNVs) as described in the healthy population are purported to contribute significantly to genetic heterogeneity. Recent studies have described CNVs using lymphoblastoid cell lines or by application of specifically developed algorithms to interrogate previously described data. However, the full extent of CNVs remains unclear. Using high-density SNP array, we have undertaken a comprehensive investigation of chromosome 18 for CNV discovery and characterisation of distribution and association with chromosome architecture. We identified 399 CNVs, of which loss represents 98%, 58% are less than 2.5 kb in size and 71% are intergenic. Intronic deletions account for the majority of copy number changes with gene involvement. Furthermore, one-third of CNVs do not have putative breakpoints within repetitive sequences. We conclude that replicative processes, mediated either by repetitive elements or microhomology, account for the majority of CNVs in the healthy population. Genomic instability involving the formation of a non-B structure is demonstrated in one region.

NTproBNP concentrations in healthy children.

INTRODUCTION: There have been limited studies generating BNP and NT-proBNP reference intervals for paediatric populations. We prospectively assessed NT-proBNP levels in a cohort of 854 healthy school children from the Lifestyle of Our Kids (LOOK) prospective longitudinal study. MATERIALS AND METHODS: NT-proBNP analysis was performed on 172 girls and 212 boys with average age 8.1 years, 183 girls and 181 boys, average age 10.1 years and 183 girls and 180 boys with average age 11.9 years. Data were stratified according to age and gender with the median, range of results and 2.5th and 97.5th percentiles calculated RESULTS: There were no significant differences between males and females at any of the 3 study ages. Significant differences were seen between the 8 and 12 year-olds, 10 and 12 year-olds and the 8 and 12 year-old boys. DISCUSSION: Our study demonstrated that NT-proBNP concentrations in healthy children progressively decline between ages 8 and 12 years. Our selection of unambiguously healthy children produced similar median but lower 97.5th percentile NT-proBNP concentrations to previously published studies.

Analytical characteristics of the Roche highly sensitive troponin T assay and its application to a cardio-healthy population.

BACKGROUND: It is desirable that current assays for cardiac troponin (cTn) are able to meet the recommended criterion that the diagnosis and risk assessment of patients present with symptoms of myocardial infarction requires a rise and fall in cTn with at least one point above the 99th percentile of a reference population. We have evaluated the analytical characteristics of the new highly sensitive troponin T (hs-TnT) assay to see if it meets this criterion and applied it to a carefully defined, cardio-healthy Australian reference population. METHODS: An imprecision profile was determined for the Roche hs-TnT assay (Roche Diagnostics, Sydney, Australia) using multiple samples analysed on nine separate occasions. The distribution of troponin T was determined using 104 samples from a cardio-healthy population. RESULTS: The new hs-TnT assay meets the specifications of a coefficient of variation of 10% at the 99th percentile of our cardio-healthy reference population. Of the 104 samples analysed 44 showed troponin T concentrations above the manufacturer's quoted limit of detection. Age and gender differences in the median and 99th percentile troponin T concentration were observed. CONCLUSIONS: The new hs-TnT assay shows improved precision and sensitivity at very low troponin concentration. We have shown that a significant number of individuals in this cardio-healthy population had detectable circulating troponin concentration. With many apparently healthy people having detectable troponin, clinical judgement will become more important in interpreting troponin results.

Prognostic efficacy of cardiac biomarkers for mortality in dialysis patients.

BACKGROUND: The high prevalence of cardiovascular mortality in the end-stage renal disease population is well established. The aim of this current study was to document the relative prognostic significance of established cardiac biomarkers troponin T (TnT), troponin I (TnI), B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro-BNP) in this population. METHODS: A prospective cohort study of dialysis patients undertaken in a single tertiary centre in Australia. Relevant clinical and biochemical information was collected at entry and all patients followed up prospectively without any loss to follow up. End-point of interest was all-cause mortality. Statistical analysis using Cox proportional hazards was used to study relationship between competing covariates and outcome. A total of 143 patients with a mean age of 59.67 +/- 15.49 years was followed up for a median duration of 30 months. Of these patients, 89.3% were white Australians of European ancestry. Twenty-seven per cent had an established diagnosis of diabetes mellitus. The mean concentrations (+/-SD) of TnT, TnI, BNP and N-terminal peptide pro-BNP (NT-pro-BNP) were 0.08 +/- 0.04 microg/L, 0.09 +/- 0.2 microg/L, 270 +/- 117 ng/L and 1434 +/- 591 ng/L respectively. RESULTS: Twenty-eight subjects died during the period of follow up. By univariate analysis, all cardiac markers (TnT, TnI, BNP, NT-pro-BNP and C-reactive protein) were significantly associated with an increase in mortality. On Cox proportionate hazards analysis, only albumin and NT-pro-BNP showed a significant association with mortality, with hazard ratios of 0.834, 95% confidence interval (CI) 0.779-0.893, P < 0.001, and 1.585, 95%CI 1.160-20165, P = 0.004 respectively. CONCLUSION: In patients with end-stage renal failure on dialysis NT-pro-BNP provides greater prognostic information compared with TnT and TnI.

The comparative analytical performance of four troponin I assays at low concentration.

BACKGROUND: Low troponin concentrations have been shown to be informative in the prognosis of acute coronary syndrome. We have investigated the analytical performance of four commonly used cardiac troponin I methods at concentrations approaching their analytical limit of detection. METHOD: We assayed 167 patient samples within 24 h of collection using the Beckman Coulter AccuTnI, Dade Behring Dimension, Abbott AxSYM and Bayer Centaur methods and compared their relative analytical performance. RESULTS: Of the four assays compared, the AccuTnI was observed to have greater sensitivity at low concentrations. Using the limit of detection as the threshold, the Beckman assay showed superior performance at concentrations corresponding to a 20% coefficient of variation (CV), the Dade assay had a similar performance; and at concentrations corresponding to 10% CV most assays provide similar information. CONCLUSION: The newer or recently modified assays such as the Beckman Coulter AccuTnI and Dade Behring assays are best able to identify very low concentrations of troponin.

The pharmacokinetics of Simplex-tobramycin bone cement.

We prospectively investigated a consecutive series of ten patients undergoing a cemented primary total hip replacement (THR) for osteoarthritis in order to establish the elution characteristics of Simplex-tobramycin bone cement (Howmedica, Limerick, Ireland). Specimens of blood, urine and drainage fluid were collected for 72 hours postoperatively. Very high concentrations of tobramycin were found in the drainage fluid, with mean levels at one hour of 103 mg/l, which steadily declined to 15.1 mg/l after 48 hours. The mean serum tobramycin levels reached a peak of 0.94 mg/l at three hours and declined rapidly to 0.2 mg/l by 48 hours. The mean urinary tobramycin levels peaked at 57.8 mg/l at 12 hours with a rapid decline to 12.6 mg/l by 24 hours. There was a direct correlation between the amount of tobramycin bone cement which was implanted and the amount of tobramycin systemically absorbed. Excellent local delivery was achieved with minimal systemic concentrations. Simplex-tobramycin bone cement is an efficient and safe method for the delivery of antibiotics after THR.

Phosphoglucomutase 1 (PGM1) subtypes and ESD types in mothers and newborns from the island of Tasmania, Australia.

PGM1 subtypes and ESD phenotypes of 600 mothers and their respective newborn infants residing in the northern part of the island of Tasmania were examined. The allele frequencies of PGM1 in the mothers were 1+ = 0.6525, 1- = 0.1250, 2+ = 0.1758 and 2- = 0.0467, and in the newborns were 1+ = 0.6675, 1- = 0.1275, 2+ = 0.01600 and 2- = 0.0450. Both samples were found to exhibit Hardy-Weinberg equilibrium conditions and there was no significant difference between them. Also, the frequencies of PGM1 alleles were overall similar to frequencies in neighbouring populations on the Australian mainland. The frequency of ESD*2 in both samples was similar (0.105) but the mothers' genotypes were not in Hardy-Weinberg equilibrium (due to an excess of type 2). The ESD allele frequencies in Tasmania are similar to those reported in other white Australian populations.