Pathwest Royal Perth Hospital

Perth, Australia

Pathwest Royal Perth Hospital

Perth, Australia

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Glendenning P.,PathWest Royal Perth Hospital | Glendenning P.,University of Western Australia | Inderjeeth C.A.,University of Western Australia | Inderjeeth C.A.,North Metropolitan Health Service
Critical Reviews in Clinical Laboratory Sciences | Year: 2016

A dramatic and sustained surge in vitamin D test numbers has been attributed to the extraskeletal and probable intra/paracrine effects of vitamin D and not the important role of vitamin D in the regulation of extracellular calcium homeostasis and bone metabolism. This review summarizes recent data regarding the skeletal and extraskeletal effects of vitamin D, provides an overview of current methods of 25-hydroxyvitamin D measurement and includes the beneficial and adverse effects of vitamin D replacement. The role of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, vitamin D binding protein and free hormone levels are explored and potential future developments in this area are discussed. The adoption of a reference method for the measurement of 25-hydroxyvitamin D, certified reference standards and an independent certification program administered by the Centre of Disease Control is expected to improve routine analytical performance and is a major, crucial step forward. Improvements in accuracy, precision and sensitivity of 25-hydroxyvitamin D measurement is an important prelude to accurately defining the desirable level of 25-hydroxyvitamin D that is associated with the lowest risk for falls and fractures. Finally, the results of ongoing large, prospective, randomized clinical trials such as the Australian D-Health study should clarify the role of vitamin D supplementation in the prevention and management of skeletal and nonskeletal disorders, including vitamin D effects on mortality risk. © 2015 Taylor & Francis.


Inderjeeth C.A.,North Metropolitan Health Service | Inderjeeth C.A.,University of Western Australia | Glendenning P.,University of Western Australia | Glendenning P.,PathWest Royal Perth Hospital | And 3 more authors.
International Journal of Women's Health | Year: 2015

Several second-generation bisphosphonates (BPs) are approved in osteoporosis treatment. Efficacy and safety depends on potency of farnesyl pyrophosphate synthase (FPPS) inhibition, hydroxyapatite affinity, compliance and adherence. The latter may be influenced by frequency and route of administration. A literature search using “ibandronate”, “postmenopausal osteoporosis”, “fracture”, and “bone mineral density” (BMD) revealed 168 publications. The Phase III BONE study, using low dose 2.5 mg daily oral ibandronate demonstrated 49% relative risk reduction (RRR) in clinical vertebral fracture after 3 years. Non-vertebral fracture (NVF) reduction was demonstrated in a subgroup (pretreatment T-score ≤ -3.0; RRR 69%) and a meta-analysis of high annual doses (150 mg oral monthly or intravenous equivalent of ibandronate; RRR 38%). Hip fracture reduction was not demonstrated. Long-term treatment efficacy has been confirmed over 5 years. Long term safety is comparable to placebo over 3 years apart from flu-like symptoms which are more common with oral monthly and intravenous treatments. No cases of atypical femoral fracture or osteonecrosis of the jaw have been reported in randomized controlled trial studies. Ibandronate inhibits FPPS more than alendronate but less than other BPs which could explain rate of action onset. Ibandronate has a higher affinity for hydroxyapatite compared with risedronate but less than other BPs which could affect skeletal distribution and rate of action offset. High doses (150 mg oral monthly or intravenous equivalent) were superior to low doses (oral 2.5 mg daily) according to 1 year BMD change. Data are limited by patient selection, statistical power, under-dosing, and absence of placebo groups in high dose studies. Ibandronate treatment offers different doses and modalities of administration which could translate into higher adherence rates, an important factor when the two main limitations of BP treatment are initiation and adherence rates. However, lack of consistency in NVF reduction and absence of hip fracture data limits more generalized use of this agent. © 2015 Inderjeeth et al.


D'Orsogna L.J.,University of Western Australia | D'Orsogna L.J.,PathWest Royal Perth Hospital | D'Orsogna L.J.,Murdoch University | Nguyen T.H.O.,Monash University | And 4 more authors.
Tissue Antigens | Year: 2013

T-cell alloreactivity is generated via immune responsiveness directed against allogeneic (allo) human leucocyte antigen (HLA) molecules. Whilst the alloresponse is of extraordinary potency and frequency, it has often been assumed to be less peptide-specific than conventional T-cell reactivity. Recently, several human studies have shown that both alloreactive CD8+ and CD4+ T cells exhibit exquisite allo-HLA and endogenous peptide specificity that has also underpinned tissue-specific allorecognition. In this review, we summarize former and recent scientific evidence in support of endogenous peptide (self-peptide)-dependence of T-cell alloreactivity. The clinical implications of these findings will be discussed in the context of both solid organ transplantation and haematopoietic stem cell transplantation (HSCT). Insights into the understanding of the molecular basis of T-cell allorecognition will probably translate into improved allograft survival outcomes, lower frequencies of graft vs host disease and could potentially be exploited for selective graft vs leukaemia effect to improve clinical outcomes following HSCT. © 2013 John Wiley & Sons Ltd.


Lee M.K.V.,Royal Perth Hospital | Vasikaran S.,PathWest Royal Perth Hospital | Doery J.C.G.,Monash University | Wijeratne N.,Monash University | Prentice D.,Royal Perth Hospital
Postgraduate Medical Journal | Year: 2013

Introduction A standard short Synacthen test (SST) is the conventional diagnostic test for primary hypoadrenalism. Measuring simultaneous plasma cortisol and adrenocorticotrophin hormone (ACTH) and using the cortisol: ACTH ratio as a first-line test may be safer and more convenient than performing a SST. Methods A retrospective study of 349 patients who had a SST with simultaneous baseline plasma cortisol and ACTH performed between 2005 and 2010 in two separate Australian health centres. The plasma cortisol: ACTH ratio was calculated for each patient and their final diagnosis was determined based on their SST result and a review of their clinical notes. Results Eighteen patients had primary hypoadrenalism, 46 patients had secondary hypoadrenalism and 285 patients had normal adrenal function. All the patients with primary hypoadrenalism had a plasma cortisol: ACTH ratio <3, while none of the patients with normal adrenal function or secondary hypoadrenalism had a cortisol: ACTH ratio <3. Therefore, a cortisol: ACTH ratio <3 had a 100% sensitivity and specificity for the diagnosis of primary hypoadrenalism. Patients with secondary hypoadrenalism had a cortisol: ACTH ratio >3, while subjects with normal adrenal function had a cortisol: ACTH ratio >15. There was overlap in cortisol: ACTH ratios of patients with secondary hypoadrenalism and normal adrenal function. Conclusions Although the cortisol: ACTH ratio predicts primary hypoadrenalism, its value is limited to diagnosing primary hypoadrenalism as it does not distinguish secondary hypoadrenalism from normal adrenal function. Larger prospective studies that include patients with early primary hypoadrenalism are needed to confirm the reliability of plasma cortisol: ACTH ratio as a diagnostic test for primary hypoadrenalism.


Wu J.-S.,University of Western Australia | James I.,Murdoch University | Qiu W.,University of Western Australia | Castley A.,PathWest Royal Perth Hospital | And 5 more authors.
Journal of Neuroimmunology | Year: 2010

Susceptibility to multiple sclerosis (MS) has been consistently associated with the Human Leukocyte Antigen (HLA)-DRB1*1501 genotype, however effects on disease severity and clinical outcome have varied in different populations. We present the results of a high-resolution HLA-DRB1 genotyping and genotype-phenotype correlation study in a large West Australian MS cohort. Our findings indicate that in this population, which is of largely Anglo-Celtic and Northern European origin, HLA-DRB1*1501 is not only a strong determinant of disease risk but may also be associated with disease severity as measured by the Multiple Sclerosis Severity Score (MSSS), with the MSSS increasing by an estimated 0.51 per DRB1*1501 allele. We also found evidence that the HLA-DRB1*1201 allele is associated with less severe disease. © 2009 Elsevier B.V.


Kirke A.B.,University of Western Australia | Barbour R.A.,University of Western Australia | Burrows S.,University of Western Australia | Bell D.A.,University of Western Australia | And 7 more authors.
Heart Lung and Circulation | Year: 2015

Background: Familial hypercholesterolaemia (FH), a co-dominantly inherited disease of cholesterol that markedly increases risk of premature coronary artery disease (CAD), is significantly under-diagnosed. Primary health care is increasingly seen as a setting in which to increase the detection rate of index cases. We report a prospective study of three methods of case detection using pre-existing primary health care services in one community. Methods: Three methods of case detection were tested: pathology laboratory database search, workplace health checks and general practice database search. People identified at risk by each of the three screening methods were offered detailed assessment for FH using the Dutch Lipid Clinic Network Criteria score (DLCNCS). Results: 1316 participants underwent detailed assessment for FH. The proportion of at risk people identified for further assessment was in decreasing order: GP (659 of 2494, 26.4%), workplace assessment (60 of 268, 22.4%) and pathology database (597 of 4517, 13.2%) p. <. 0.001. Eight-six (6.5%) were identified as clinical FH (DLCNCS. >. 5) of which 59 had genetic testing and 11 of 59, 18.6%, were confirmed to have a mutation causing FH. Pathology database detected the greatest number of clinical FH (51 of 86, 59.3%) and mutation positive participants (8 of 11, 72.7%). Conclusion: Screening within primary health care was successful in detecting participants with FH. An integrated case detection model combining screening of pathology and GP databases is proposed. © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).


Bell D.A.,University of Western Australia | Bell D.A.,PathWest Royal Perth Hospital | Bell D.A.,Royal Perth Hospital | Hooper A.J.,University of Western Australia | And 10 more authors.
Atherosclerosis | Year: 2014

Objective: To determine whether a telephone call from a chemical pathologist to the requesting general practitioner (GP) of individuals at high risk of familial hypercholesterolaemia (FH) increases specialist referral and detection of FH. Method: Individuals with an LDL-cholesterol ≥6.5mmol/L without secondary causes were identified from a community laboratory; 100 cases and 96 historical controls. All laboratory reports (cases and controls) received interpretative comments highlighting FH. In addition, the cases' GPs received a telephone call from the chemical pathologist to highlight their patient's risk of FH and suggest specialist referral, whereas with the controls' GPs were not telephoned. Results: After 12 months follow-up, 27 (27%) cases were referred to clinic compared with 4 (4%) controls (p<0.0001). 25 cases were reviewed at clinic, 12 (48%) had definite FH and 18 (72%) had probable or definite FH according to the Dutch Lipid Clinic Network Criteria, 2 cases did not attend their clinic appointments. Genetic testing was performed in 23 individuals: 7 (30%) had pathogenic FH mutations. Genotypic cascade screening of 4 kindreds from the intervention group detected an additional 7 individuals with FH and excluded 5 mutation-negative family members. Conclusions: A telephone call from a chemical pathologist to the requesting GP of patients at high risk of FH was associated with significantly higher rates of FH detection and specialist referral. Over 70% of individuals with an LDL-cholesterol ≥6.5mmol/L were diagnosed with FH. However, further investigation is required to improve the relatively low referral rate. © 2014 Elsevier Ireland Ltd.


Lee J.,Catholic University of Korea | Vasikaran S.,PathWest Royal Perth Hospital
Annals of Laboratory Medicine | Year: 2012

Osteoporosis is a major health problem worldwide, and is projected to increase exponentially due to the aging of the population. The absolute fracture risk in individual subjects is calculated by the use of algorithms which include bone mineral density (BMD), age, gender, history of prior fracture and other risk factors. This review describes the laboratory investigations into osteoporosis which include serum calcium, phosphate, creatinine, alkaline phosphatase and 25-hydroxyvitamin D and, additionally in men, testosterone. Parathyroid hormone (PTH) is measured in patients with abnormal serum calcium to determine its cause. Other laboratory investigations such as thyroid function testing, screening for multiple myeloma, and screening for Cushing's syndrome, are performed if indicated. Measurement of bone turnover markers (BTMs) is currently not included in algorithms for fracture risk calculations due to the lack of data. However, BTMs may be useful for monitoring osteoporosis treatment. Further studies of the reference BTMs serum carboxy terminal telopeptide of collagen type I (s-CTX) and serum procollagen type I N-terminal propeptide (s-PINP) in fracture risk prediction and in monitoring various treatments for osteoporosis may help expedite their inclusion in routine clinical practice. © The Korean Society for Laboratory Medicine.


Chaisri S.,Khon Kaen University | Kitcharoen K.,Khon Kaen University | Romphruk A.V.,Khon Kaen University | Romphruk A.,Khon Kaen University | And 3 more authors.
Immunogenetics | Year: 2013

Killer cell immunoglobulin-like receptors (KIRs) are cell surface receptors on natural killer (NK) cells and subsets of T cells. The functions of NK cells are partly regulated by interactions between KIRs and HLA ligands on target cells. In this study, the presence or absence of 17 KIR genes and their known HLA ligands have been investigated in 235 unrelated individuals living in northeastern Thailand (NET). Subtypes of KIR2DS4 including full length (KIR2DS4F) and deleted forms (KIR2DS4D) have also been determined. Framework genes (KIR2DL4, 3DL2, 3DL3, and 3DP1) were found in all individuals and KIR genes belonging to the A haplotype (KIR2DL1, 2DL3, 3DL1, and 2DS4) were present in more than 90 % of NET. KIR2DS4D (61.7 %) was more common than KIR2DS4F (52.8 %). A total of 33 different KIR genotypes were observed. Of these, three new genotypes were identified. The most common genotype (AA) was observed in 35.7 % of NET, and HLA-C alleles bearing the C1 epitope (HLA-C1) had the highest frequency (97 %). All individuals had at least one inhibitory KIR and its corresponding HLA ligand; 40.9 % of NET had three pairs of receptor-ligand combinations, and 18.3 % had all three receptor-ligand combinations of KIR2DL3+C1, 3DL1+Bw4, and 3DL2+A11. Surprisingly, the patterns of KIR gene frequencies in NET are more similar to those of Caucasians than Japanese, Korean, and Chinese. This is the first report on complete analysis of KIR and known HLA ligands in Thais. These data provide basic knowledge on KIR for further studies on disease associations and transplantation in northeastern Thais. © 2013 Springer-Verlag Berlin Heidelberg.


PubMed | Pathwest Royal Perth Hospital and University of Western Australia
Type: Journal Article | Journal: Annals of clinical biochemistry | Year: 2016

The presence of C3-epimer (C-3-epi-25-hydroxyvitamin D) in infant serum may complicate 25-hydroxyvitamin D (25(OH)D) measurement when using liquid chromatography tandem mass spectrometry assays that do not separately measure the epimer. We measured the concentration of C3-epi-25(OH)D in neonatal samples in Western Australian using umbilical cord blood samples and a liquid chromatography tandem mass spectrometry assay that separately quantifies 25(OH)D and C3-epi-25(OH)D.A total of 120 anonymized cord blood samples were analysed using a liquid chromatography tandem mass spectrometry assay that utilizes two CSH fluoro-phenyl columns in series. Chromatography was performed on a Waters Acquity Ultra Performance Liquid system, and quantification was using a Waters Quattro Premier XE mass spectrometer.C3-epi-25(OH)D3 was detected in all umbilical cord blood samples (median 5.2nmol/L, IQR 3.7-6.6nmol/L) and contributed 6.6% (SD 2.6, 95% CI [6.1, 7.1]) of the total 25(OH)D concentration. Mean 25(OH)D3 measured in cord blood was 79.1nmol/L (SD 22.7nmol/L). A positive relationship (R(2)=0.35, P<0.0005) between 25(OH)D3 levels and C3-epi-25(OH)D3 was noted in this cohort. No samples contained 25(OH)D2 or C3-epi-25(OH)D2.C3-epi-25(OH)D3 is present in all neonatal samples but contributes <10% of the total 25(OH)D concentration which is unlikely to be clinically significant. Liquid chromatography tandem mass spectrometry assays that do not separately quantify C3-epi-25(OH)D3 from other vitamin D metabolites may potentially overestimate neonatal 25(OH)D levels, but diagnostic misclassification in neonates is unlikely.

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