ORCID Profile
0000-0002-6048-8744
Current Organisation
Alfred Health
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Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.SEMNEPHROL.2011.11.002
Abstract: Chronic heart failure and chronic renal failure are at epidemic proportions. These patients have significantly altered cardiac, renal, and all-cause outcomes. Much of the current research has focused on treating these in idual organs in isolation. Although there are positive data on outcomes with neurohormonal modulation, they, however, remain underused. At present, data lacks for novel treatment options, while evidence continues to point at significantly worsened prognosis. Current diagnostic tools that detect acute changes in renal function or renal injury appear retrospective, which often hinder meaningful diagnostic and therapeutic decisions. This review is aimed at exploring the importance of accurate assessment of renal function for the heart failure patient by providing a synopsis on cardio-renal physiology and establishing the possibility of novel approaches in bridging the ide.
Publisher: Georg Thieme Verlag KG
Date: 11-1987
Abstract: Some effects of calcitonin (CT) can also be produced by calcitonin gene-related peptide (CGRP), an alternative product of the calcitonin gene. This might be mediated by interaction of CGRP at the CT-receptor site. The human breast cancer cell line T47D possesses well characterized CT-receptors (KD = 2.3 x 10(-10) M for 125I salmon CT). 50% inhibition of 125I-sCT binding was achieved with 10(-9) M sCT, 5 x 10(-6) M rat CGRP and 10(-5) M human CGRP. Half maximal cAMP production in T47D cells was seen with 6 x 10(-10) M sCT, 5 x 10(-6) M rCGRP and 10(-5) M hCGRP. Binding and displacement capacity as well as the biological activity of CT and CGRP seems to correlate well. These findings suggest that CGRP in pharmacological doses acts via the CT-receptor. This could be explained by the homology and conformational similarities between CT and CGRP.
Publisher: AMPCo
Date: 07-2011
DOI: 10.5694/J.1326-5377.2011.TB03190.X
Abstract: An international consensus statement recommends that dual reporting of haemoglobin A (HbA(1c)) levels--in the current units (percentage) and Système International (SI) units (mmol/mol)--be used as an interim measure for a 2-year transition period before progressing towards the use of SI units only. This recommendation is supported by the Australasian Association of Clinical Biochemists, the Australian Diabetes Educators Association, the Australian Diabetes Society and the Royal College of Pathologists of Australasia. The SI units are a true measure of HbA(1c) and remove potential confusion between HbA(1c) values and blood glucose values.
Publisher: Wiley
Date: 02-2021
DOI: 10.1111/IMJ.15183
Publisher: Elsevier BV
Date: 06-2011
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.BONE.2013.04.003
Abstract: This study was performed to establish age-related serum reference intervals for procollagen type I N-propeptide (P1NP) and type I collagen C-telopeptide (CTx) in the Australian population. Fasting sera from 1143 males (mean age 60 years range 20-97 years) and 1246 females (mean age 53 years range 20-93 years) who participated in the Geelong Osteoporosis Study were analysed for CTx and P1NP using the automated Roche Modular Analytics E170 analyser. Optimal age-related reference intervals were based on the central 90% of the distribution. The male CTx reference interval was ided into three age groups. For men aged 25 to 40 years, the interval was 170-600 ng/L 40 to 60 years, the interval was 130-600 ng/L and for men aged greater 60 years the interval was 100-600 ng/L. For P1NP the male reference interval was 15-80 μg/L for men aged between 25 to 70 years. In men greater than 70 years of age values were higher possibly due to increased bone turnover. High values are frequently seen for both CTx and P1NP in males aged younger than 25 years. This is probably due to bone growth that is not completely finalised. The female CTx reference interval was ided into four age groups. For women aged less than 30 years, the interval was 150-800 ng/L 30-39 years, the interval was 100-700 ng/L 40-49 years, the interval was 100-600 ng/L and for women aged 50 years or more the interval was 100-700 ng/L. The female P1NP reference interval was ided into four age groups. For women aged less than 30 years, the interval was 25-90 μg/L 30-39 years, the interval was 15-80 μg/L 40-49 years, the interval was 15-60 μg/L and for women aged 50-69 years the interval was 15-75 μg/L. In women greater than 70 years of age values were higher possibly due to increased bone turnover. Values obtained from this large study provide sound age-related reference intervals for serum P1NP and CTx values in the Australian population.
Publisher: Wiley
Date: 09-2004
DOI: 10.1111/J.1445-5994.2004.00671.X
Abstract: Background : Serum tumour markers (TM) are often measured in hospital patients. The reasons for their use and their benefits with regards to earlier cancer diagnosis and patient management are not known. Aims : To identify the patterns of TM use in a tertiary hospital and to determine the usefulness and appropriateness of requests in this setting. Methods : A cross‐sectional, retrospective study of TM ordered over a 3‐month period was conducted. Data were obtained from patient records. CA‐125, CA 15‐3, CA 19‐9, carcinoembryonic antigen (CEA), and alpha‐fetoprotein (AFP) were studied. Prostate specific antigen was not separately investigated. The reasons for ordering, usefulness and appropriateness of use were defined prior to analysis. Results : A total of 476 TM was ordered in 373 patients. One hundred and six (22%) of all results were abnormal by laboratory criteria. AFP was the most popular test ordered. Forty‐seven per cent of patients had no cancer diagnosis. Oncological units (ONC) ordered 27% of tests. The most popular reasons for TM ordering were for screening (36%) followed by diagnostic aid (19%). ONC units ordered TM mainly for monitoring disease status, as opposed to non‐ONC units who ordered TM usually for diagnostic aid. TM were deemed appropriately ordered in 69% of cases. Twenty‐nine per cent of TM were helpful in patient management. Only four results ( %) aided in diagnosis. Conclusions : The reasons and appropriateness of TM use varied depending on the specialization of the requesting clinician. The current serum TM are most useful as aids in cancer patients, rather than for diagnosis ( P 0.0001). Apart from AFP, these TM seem to have limited use in the general medical, non‐oncological patients. Guidelines for their use in this setting are needed. (Intern Med J 2004 34: 545−550)
Publisher: Georg Thieme Verlag KG
Date: 16-07-1991
Abstract: To study work-related physical and psychosocial risk factors for sick leave among patients who have visited their general practitioner for neck or upper extremity complaints. Three hundred and forty two patients with neck or upper extremity complaints completed self-report questionnaires at baseline and after 3 months. Cox regression models were used to investigate the association between work-related risk factors and sick leave (i.e., lost days from work due to neck or upper extremity complaints in 3 months). Effect modification by sick leave at baseline, sex, worrying and musculoskeletal co-morbidity was evaluated by adding product terms to the regression models. In the subgroup of patients who scored high on the pain copying scale "worrying" the hazard ratio of sick leave was 1.32 (95% CI 1.07-1.62) per 10% increase in heavy physical work. The subgroup of patients who were sitting for long periods of time had a reduced risk of sick leave as compared to patients who did not spend a lot of time sitting, again only in patients who scored high on the pain coping scale "worrying" (adjusted HR=0.17, 95%-CI 0.04-0.72). Other work-related risk factors were not significantly related to sick leave. Heavy physical work increased the risk of sick leave and prolonged sitting reduced the risk of sick leave in a subgroup of patients who worried much about their pain. Additional large longitudinal studies of sufficiently large size among employees with neck or upper extremity complaints are needed to confirm our results.
Publisher: Oxford University Press (OUP)
Date: 05-2019
Publisher: Wiley
Date: 08-05-2022
DOI: 10.1111/DME.14841
Publisher: Elsevier BV
Date: 08-2007
DOI: 10.1080/00313020701444564
Abstract: Procalcitonin measurement has been claimed as a helpful marker in bacterial infection and sepsis. It has obtained FDA approval and is now widely marketed in the United States and Europe. This review summarises the current assays available, the evidence for its use and possible future applications of the assay.
Publisher: Elsevier BV
Date: 07-1988
DOI: 10.1016/0303-7207(88)90048-2
Abstract: T47D cells possess specific calcitonin (CT) receptors and a CT-responsive adenylate cyclase. Internalization of part of their CT receptors has been suggested. At 37 degrees C, bound 125I-labelled salmon CT (sCT) becomes increasingly resistant to acid washing, which can remove surface-bound hormone, thus indicating internalization. Monensin and chloroquine, which raise the pH of the lysosomes and thereby inhibit cellular processing of endosomes, inhibit the decrease of total bound activity seen in the controls. Acid-resistant (internalized) activity increases to the levels of total binding. Preincubation with sCT leads to a loss of specific binding. Recovery of CT binding is prevented by monensin, which also inhibits transport of cellular proteins to the cell membrane. Recovery is not influenced by chloroquine. As chloroquine prevents recycling, we conclude that after binding of CT the receptors are internalized, transferred to a lysosomal compartment, and degraded intracellularly without recycling. All receptors seem to undergo internalization. Desensitization to CT in T47D cells is at least partly mediated by intracellular metabolism of CT receptors.
Publisher: Wiley
Date: 17-09-2023
Publisher: Elsevier BV
Date: 04-1992
DOI: 10.1016/0169-6009(92)90711-L
Abstract: The human breast cancer cell line T 47 D expresses calcitonin (CT) receptors that are coupled to adenylate cyclase and which reveal a dose-dependent cyclic AMP response to CT. We used this model to establish an in vitro bioassay for synthetic human CT (hCT) preparations to overcome some of the obstacles of the standard rat hypocalcemia in vivo bioassay. The detection limit of the in vitro bioassay was 1 x 10(-10) M hCT (EC 50: 8.7 pM +/- 26%) compared to 7.3 x 10(-9) M (EC 50: 7.2 microM +/- 32%) for the in vivo bioassay. The relative potencies of test preparations revealed a good correlation (r = 0.89) and several hCT-related substances produced comparable results when tested by the two methods. The standard deviations of precision and accuracy, however, were significantly smaller (P less than 0.05) for the in vitro bioassay. According to these data the T 47 D in vitro bioassay is more sensitive, superior in precision and accuracy, and comparable in specificity to the rat hypocalcemia bioassay.
Publisher: Portland Press Ltd.
Date: 1991
DOI: 10.1042/BJ2730179
Abstract: In this study we have solubilized and characterized binding sites for calcitonin (CT) from sheep brainstem. Autoradiography of 125I-labelled salmon CT (125I-sCT) binding to sheep diencephalon revealed a similar pattern of binding to that seen in other species, although the extent of distribution was greater in the sheep. CT binding activity could be extracted from membranes with either CHAPS or digitonin, but not with β-octyl glucoside, 125I-sCT binding was saturable, with a dissociation constant for CHAPS-solubilized membranes of 2.8 +/- 0.5 nM and a maximum binding site concentration of 6.2 +/- 1.6 pmol/mg of protein. In competition binding studies, various CTs and their analogues demonstrated a similar rank order of potency to that seen in other CT receptor systems, Optimal binding occurred in the pH range 6.5-7.5, and was decreased in the presence of NaCl concentrations greater than 200 mM. In contrast with most other CT receptor binding systems, in which binding is poorly reversible, the binding of 125I-sCT to sheep brain binding sites underwent substantial dissociation upon addition of excess unlabelled sCT, with 40% and 46% dissociation after 2 h at 4 degree C in particulate and solubilized membranes respectively. Photoaffinity labelling of the binding site with the biologically active analogue 125I-[Arg11,18,4-azidobenzoyl-Lys14]sCT and analysis on SDS/PAGE under reducing conditions revealed a specific protein band of Mr approximately solubilized and particulate brain membranes. This is in accordance with the molecular size of CT receptors in other tissues where two species of receptor have been identified. one of Mr approximately 71,000 and another of Mr approximately 88,000. These results demonstrate the presence of high concentrations of CT binding sites in sheep brain which display different kinetic properties to those of CT receptors found in other tissues.
Publisher: The Endocrine Society
Date: 09-1992
DOI: 10.1210/ENDO.131.3.1324161
Abstract: Transforming growth factor-beta (TGF beta) produced by osteoblasts is present in high levels in bone and influences bone formation, replication of bone cells, and expression of osteoblast protein products. Interactions between bone active hormones and locally released and activated TGF beta were studied by examining the influence of TGF beta preincubation on PTH, calcitonin (CT), and vitamin D receptors in an osteoblastic cell line (UMR 106-06). Preincubation of UMR 106-06 cells with 1 ng/ml TGF beta for 3 days increased specific binding of [125I]PTH-related protein (PTHrP)(1-84) to 140% of that in control cells, but [125I]salmon CT binding decreased to 50% of controls. Binding isotherms indicated that the changes in binding were due to altered receptor numbers since affinities for 125I-labeled PTH and CT remained unchanged. The effect on receptor levels was time dependent, requiring 24 h preincubation with TGF beta for measurable changes, and dose dependent, with maximal effects seen with 1 ng/ml TGF beta. Binding of [3H]1,25(OH)2 vitamin D3 was increased to 130% of control in cytosolic extracts of UMR 106-06 cells pretreated for 3 days with 1 ng/ml TGF beta. Scatchard plots suggested an increase in receptor number without change in affinity. The adenylate cyclase response to PTH increased to 150% of control cells after 3 days of treatment with 1 ng/ml TGF beta however, the adenylate cyclase response to CT was little changed. Forskolin- and cholera toxin-stimulated adenylate cyclase responses were increased by TGF beta treatment to 130-160% of control, indicating an increase in the stimulatory subunit of the G protein. Increased abundance of both Gs and Gi proteins were indicated by increased cholera toxin- or pertussis toxin-dependent [32P] NAD ribosylation of 47-kilodalton (kDa) and 42-kDa or 40-kDa proteins, respectively, in TGF beta-treated cells. Our data support a complex regulatory effect of TGF beta on UMR 106-06 cells with increases in PTH receptors, vitamin D receptors, and G proteins, whereas there is an apparent down-regulation of CT receptors. TGF beta might induce a more differentiated osteoblast phenotype of these cells, which already express differentiated features such as high alkaline phosphatase activity, PTH and vitamin D receptors, and collagenase production. Since low doses of PTH stimulate bone formation in vivo, TGF beta released or activated at sites of new bone formation might locally modulate PTH activity be allowing increased PTH receptor and postreceptor effectiveness.
Publisher: SAGE Publications
Date: 07-2016
Publisher: Springer Science and Business Media LLC
Date: 28-01-2009
DOI: 10.1007/S00520-009-0584-8
Abstract: Soluble transferrin receptor (sTfR) reflects erythropoietic activity in the bone marrow. We have sought to identify whether serial measurement of sTfR may predict depth or duration of myelosuppression in patients receiving high dose chemotherapy. We prospectively measured serial sTfR in nine consecutive patients with haematologic malignancy admitted for various high dose regimens. The sTfR nadir was associated with white cell nadir, and sTfR nadir and day 5 sTfR were inversely associated with the number of red cell transfusions required. Our data suggest that sTfR may be helpful in predicting the degree of bone marrow suppression in patients receiving intensive chemotherapy.
Publisher: Walter de Gruyter GmbH
Date: 2016
Abstract: Monoclonal gammopathies are characterised by the production of a monoclonal immunoglobulin or free light chains by an abnormal plasma cell or B-cell clone and may indicate malignancy or a precursor (MGUS). There is currently no consensus on the initial test or combination of tests to be performed in suspected monoclonal gammopathies but serum protein electrophoresis and urine protein electrophoresis are commonly requested as initial investigations. If abnormal, immunofixation electrophoresis is then performed to confirm the presence of paraprotein and to determine its heavy and light chain type. Recently, some groups have developed simplified “screening” IFE methods for use in parallel to SPEP for the detection monoclonal gammopathies. We argue here that screening IFE may be of benefit in clinical laboratories using SPEP with poor resolution in the β-region, assisting in the detection of mainly IgA paraprotein, but may be of less benefit in laboratories utilising higher resolution gels. Further it may increase the detection of trace bands of questionable clinical significance, representing transient phenomena in infectious and auto-immune conditions or very low risk MGUS. The increased detection of these bands using screening IFE would require further patient follow up, possibly causing unnecessary patient anxiety and additional follow up healthcare costs.
Publisher: Walter de Gruyter GmbH
Date: 2007
Publisher: Springer Science and Business Media LLC
Date: 24-11-2022
DOI: 10.1007/S00198-022-06597-3
Abstract: Low serum alkaline phosphatase (ALP) was found in 9% of patients attending an osteoporosis clinic, 0.6% of hospital patients, and 2/22 with an atypical femoral fracture. Hypophosphatasia was diagnosed in 3% of osteoporosis clinic patients with low ALP. Low ALP is a screening tool for hypophosphatasia, a condition potentially aggravated by antiresorptive therapy. Hypophosphatasia (HPP) is an inherited disorder associated with impaired primary mineralisation of osteoid (osteomalacia). HPP may be misdiagnosed as osteoporosis, a reduction in the volume of normally mineralized bone. Both illnesses may result in fragility fractures, although stress and atypical fractures are more common in HPP. Antiresorptive therapy, first-line treatment for osteoporosis, is relatively contraindicated in HPP. Misdiagnosis and mistreatment can be avoided by recognising a low serum alkaline phosphatase (ALP). Our aim was to determine the prevalence of a low ALP (< 30 IU/L) in patients attending an osteoporosis clinic, in a hospital-wide setting, and in a group of patients with atypical femoral fractures (AFF). This was a retrospective study of patients attending an osteoporosis clinic at a tertiary hospital during 8 years (2012-2020). Patients were categorised into those with a transiently low ALP, those with low ALP on ≥ 2 occasions but not the majority of measurements, and those with a persistently low ALP. ALP levels were also assessed in hospital-wide records and a group of patients with AFF. Of 1839 patients attending an osteoporosis clinic, 168 (9%) had ≥ 1 low ALP, 50 (2.7%) had low ALP for ≥ 2 months, and seven (0.4%) had persistently low ALP levels. HPP was diagnosed in five patients, four of whom had persistently low ALP levels. The prevalence of HPP was 0.3% in the osteoporosis clinic and 3% in patients with ≥ 1 low ALP. Low ALP occurred in 0.6% of all hospital patients and 2/22 with AFF. Persistently low ALP in osteoporosis clinic attendees is easy to identify and signals the possibility of hypophosphatasia, a condition that may be mistaken for osteoporosis and incorrectly treated with antiresorptive therapy.
Publisher: Wiley
Date: 11-2020
DOI: 10.1111/IMJ.14720
Abstract: Australian hospital data on hyperglycaemia without previously known diabetes are lacking. To determine the prevalence of hyperglycaemia without previously recognised diabetes among all patients screened in the emergency department (ED). Secondary aims are to describe the extent of haemoglobin A1c testing for evaluation of new diabetes, adequate glucose monitoring, treatment of significant hyperglycaemia and documented follow-up plans. Patients presenting to ED at the Alfred (tertiary hospital in Melbourne) have undergone screening random plasma glucose (RPG) with their first plasma biochemistry since 2015. Of the 16 268 adults screened from July to December 2015, a retrospective, cross-sectional study was undertaken evaluating those with hyperglycaemia (RPG >7.8 mmol/L) but without previously recognised diabetes as determined from coding data. After patient records were reviewed to correct for coding errors, a nested cohort of 200 such patients were further evaluated. Glucose monitoring was deemed adequate if undertaken for ≥48 h. Significant hyperglycaemia (RPG >11 mmol/L) was considered appropriately treated if insulin/hypoglycaemic agents were prescribed. Documented follow-up plans were acceptable if found in the discharge summary. Among all patients screened, 1178 had hyperglycaemia without coded diabetes. After adjusting for coding errors, the prevalence was 5.2%. Within the nested cohort, only 7.5% had a follow-up haemoglobin A1c ordered, 9.5% underwent adequate glucose monitoring, 6.5% had appropriate treatment of significant hyperglycaemia and 2% had documentation of a follow-up plan. Hyperglycaemia without previously recognised diabetes is commonly seen and justifies ED screening. However, management of newly detected hyperglycaemia in these patients is suboptimal and requires improvement.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2017
DOI: 10.1097/FTD.0000000000000417
Abstract: Valproic acid (VPA) is a widely prescribed medicine, and acute toxicity is possible. As such, it should be included in any nontargeted urine drug screening method. In many published liquid chromatography–electrospray ionization–mass spectrometry (LC–ESI–MS/MS) methods, VPA is usually measured using a pseudo-multiple reaction monitoring (MRM) transition. We investigate a simple ultra-high-performance liquid chromatography–quadrupole time-of-flight (QTof) approach to detect the presence of VPA with more confidence. Three commercially sourced VPA metabolites were characterized and added to a nontargeted high-resolution MS urine drug screening method. All analyses were performed on a Waters Xevo G2-XS LC-QTof in negative electrospray ionization mode. The mass detector was operated in MS E mode, and data were processed with UNIFI software. Sixty-eight patient urine s les, which were previously identified by a well-established gas chromatography–MS method as containing VPA, were analyzed on the Waters Xevo G2-XS LC-QTof, to validate this approach. VPA metabolite standards were characterized, and their detection data were added to the broad drug screening library. VPA metabolites were readily detectable in the urine of patients taking VPA. The inclusion of characterized VPA metabolites provides a simple and reliable method enabling the detection of VPA in nontargeted urine drug screening.
Publisher: European Respiratory Society (ERS)
Date: 08-2004
DOI: 10.1183/09031936.04.00104803
Abstract: Iron availability is critical to Pseudomonas aeruginosa. The current authors determined sputum iron, ferritin, microalbumin levels and total cell counts (TCC) in 19 adult patients with cystic fibrosis (CF) during an acute exacerbation and repeated analyses following a median of 12 days antibiotic treatment. The current authors also determined sputum interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha levels because of their putative role in intracellular iron homeostasis. Additional data were obtained from 17 stable CF patients, eight patients with stable chronic obstructive pulmonary disease (COPD) and six normal subjects. Overall, sputum iron, ferritin, microalbumin, IL-1beta and TNF-alpha concentrations and TCCs were significantly elevated in the CF patients compared to those with COPD and normal controls. Sputum ferritin levels were significantly elevated in acute versus stable CF patients and there was a trend for sputum TCC to be higher, but all other inflammatory indices were similar. In the CF patients, sputum iron was positively and strongly related to IL-1beta, TNF-alpha, ferritin and microalbumin levels, but negatively related to forced expiratory volume in one second % predicted. In those acute patients who clinically improved with antibiotics (n=14), there were significant decreases in sputum TCC, iron, ferritin and IL-1beta content, but not TNF-alpha or albumin levels. However, changes in sputum TNF-alpha in acute patients were still closely related to changes in iron, ferritin and albumin content, and changes in IL-1beta were related to changes in sputum ferritin content. Iron and iron-regulatory cytokines may play a role in cystic fibrosis lung disease and the increased iron content may even facilitate Pseudomonas aeruginosa infection.
Publisher: Wiley
Date: 21-12-2021
DOI: 10.1111/CEN.14659
Abstract: To formulate clinical consensus recommendations on the presentation, assessment, and management of primary hyperparathyroidism (PHPT) in adults. Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence‐informed position statement addressing nine key questions. PHPT is a biochemical diagnosis. Serum calcium should be measured in patients with suggestive symptoms, reduced bone mineral density or minimal trauma fractures, and in those with renal stones. Other indications are detailed in the manuscript. In patients with hypercalcaemia, intact parathyroid hormone, 25‐hydroxy vitamin D, phosphate, and renal function should be measured. In established PHPT, assessment of bone mineral density, vertebral fractures, urinary tract calculi/nephrocalcinosis and quantification of urinary calcium excretion is warranted. Parathyroidectomy is the only definitive treatment and is warranted for all symptomatic patients and should be considered for asymptomatic patients without contraindications to surgery and with years life expectancy. In patients who do not undergo surgery, we recommend annual evaluation for disease progression. Where the diagnosis is not clear or the risk‐benefit ratio is not obvious, multidisciplinary discussion and formulation of a consensus management plan is appropriate. Genetic testing for familial hyperparathyroidism is recommended in selected patients. These clinical consensus recommendations were developed to provide clinicians with contemporary guidance on the assessment and management of PHPT in adults. It is anticipated that improved health outcomes for in iduals and the population will be achieved at a decreased cost to the community.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.CLINBIOCHEM.2013.04.016
Abstract: Troponin point of care tests have been found to have inferior sensitivity to laboratory based tests, when either the 10% CV or the 99 th percentile of a healthy population is used as the cut-off. In a prospective study we evaluated a decreased cut-off in the detection of cardiac injury. We compared 2 point of care assays (i-stat, Abbott Diagnostics and AQT 90, Radiometer) for troponin I with a laboratory assay for troponin I (ARCHITECT STAT troponin-I assay, Abbott Diagnostics), previously evaluated for diagnosis of acute coronary syndrome (ACS). We used the published 99 th percentile and a value that was 50% of that. We investigated these tests in a convenience s le of 195 patients presenting to a suburban hospital. We used chi-square tests for the comparison and a P<0.05 as significant. Clinical outcomes were obtained for patients with elevated levels of the laboratory assay. At the 99 th percentile both assays did only detect cardiac injury in a percentage of true positives compared to the laboratory test (34 and 51%) with a significant rate of false negative values (19.6 and 14.9%). Using a decreased cut-off (50% of 99 th percentile) increased detection of true positives (to 80.9 and 76.5%) with an acceptable rate of false positive results (7.3 and 7.1%) significantly (P<0.01). Clinical review showed POC tests missed 6 of 13 patients with confirmed AMI (a sensitivity of 46%) and that a lower cut-off allowed them to detect all (for the i-stat) or most (4 of 6 for the AQT) of them. We believe that we have described in this study a way to improve the sensitivity of point of care assays for troponin that allows us to identify additional patients without losing the specificity required to identify appropriate patients for discharge from the emergency department.
Publisher: Springer Science and Business Media LLC
Date: 13-07-2017
DOI: 10.1038/S41467-017-00138-X
Abstract: Atherosclerosis is a major cause of mortality and morbidity, which is mainly driven by complications such as myocardial infarction and stroke. These complications are caused by thrombotic arterial occlusion localized at the site of high-risk atherosclerotic plaques, of which early detection and therapeutic stabilization are urgently needed. Here we show that near-infrared autofluorescence is associated with the presence of intraplaque hemorrhage and heme degradation products, particularly bilirubin by using our recently created mouse model, which uniquely reflects plaque instability as seen in humans, and human carotid endarterectomy s les. Fluorescence emission computed tomography detecting near-infrared autofluorescence allows in vivo monitoring of intraplaque hemorrhage, establishing a preclinical technology to assess and monitor plaque instability and thereby test potential plaque-stabilizing drugs. We suggest that near-infrared autofluorescence imaging is a novel technology that allows identification of atherosclerotic plaques with intraplaque hemorrhage and ultimately holds promise for detection of high-risk plaques in patients.
Publisher: Wiley
Date: 12-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2011
DOI: 10.1161/CIRCHEARTFAILURE.110.960716
Abstract: Heart failure with preserved ejection fraction (HFPEF) is a common and increasing public health problem. Myocardial fibrosis is a key pathological feature of HFPEF. Peripheral collagen markers may reflect this excess fibrosis however, the relation of these markers to prognosis in patients with HFPEF has not as yet been determined. This substudy of the Irbesartan in Heart Failure With Preserved Systolic Function (I-PRESERVE) trial measured plasma levels of procollagen type I amino-terminal peptide, procollagen type III amino-terminal peptide, and osteopontin in 334 patients with HFPEF. Measurements were performed at baseline and 6 months after randomization to placebo or irbesartan 300 mg/day. The relation of baseline collagen markers to the I-PRESERVE primary end point (all-cause death and hospitalization for prespecified cardiovascular causes) was evaluated by single and multivariable analysis. Similar evaluations were performed for all-cause death alone as well as heart failure events (death or hospitalization because of heart failure). Increased plasma levels of collagen markers at baseline were associated with increased frequency of the study primary end point for all collagen markers. For each 10-μg/L increase in procollagen type I amino-terminal peptide, the hazard ratio (HR) for the primary end point was 1.09 (95% CI, 1.052 to 1.13 P .0001) for each 10-μg/L increase in procollagen type III amino-terminal peptide procollagen type I amino-terminal peptide, the HR was 2.47 (95% CI, 0.97 to 6.33 P =0.059) and for each 10-nmol/L increase in osteopontin, the HR was 1.084 (95% CI, 1.026 to 1.15 P =0.004). No variable remained significant as an independent predictor when introduced into a multivariable model. Both treatment groups tended to reduce collagen markers, with the reduction significantly greater for placebo versus irbesartan for procollagen type III amino-terminal peptide only ( P =0.0185). Increased peripheral collagen turnover markers were not independently associated with increased mortality and cardiovascular hospitalization in an HFPEF population on multivariable analysis but were associated on single-variable analysis. These findings provide some support to the hypothesis that pathological fibrosis in the heart, and possibly the peripheral vasculature, may be contributory to adverse clinical outcomes in patients with HFPEF. URL: www.clinicaltrials.gov . Unique identifier: NCT00095238.
Publisher: Elsevier BV
Date: 06-2014
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.RESUSCITATION.2012.07.025
Abstract: To estimate the ability of commonly measured laboratory variables to predict an imminent (within the same or next calendar day) death in ward patients. Retrospective observational study. Two university affiliated hospitals. Cohort of 42,701 patients admitted for more than 24 hours and external validation cohort of 13,137 patients admitted for more than 24 hours. We linked commonly measured laboratory tests with event databases and assessed the ability of each laboratory variable or combination of variables together with patient age to predict imminent death. In the inception teaching hospital, we studied 418,897 batches of tests in 42,701 patients (males 55% average age 65.8 ± 17.6 years), for a total of >2.5 million in idual measurements. Among these patients, there were 1596 deaths. Multivariable logistic modelling achieved an AUC-ROC of 0.87 (95% CI: 0.85-0.89) for the prediction of imminent death. Using an additional 105,074 batches from a cohort of 13,137 patients from a second teaching hospital, the multivariate model achieved an AUC-ROC of 0.88 (95% CI: 0.85-0.90). Commonly performed laboratory tests can help predict imminent death in ward patients. Prospective investigations of the clinical utility of such predictions appear justified.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.CLINBIOCHEM.2018.01.004
Abstract: Invasive fungal infections are an increasing cause of mortality and morbidity in high risk patient populations such as those on immunosuppressive therapy. Triazole antifungals are recommended for the prevention and treatment of such infections. The aim of this study was to develop and validate a simple, sensitive and robust LCMS/MS method for the simultaneous analysis in human plasma of three frequently used antifungal drugs: voriconazole, posaconazole, and itraconazole. Precipitation reagent, containing deuterated internal standards, is added to 50μL of plasma. The vials are vortexed before centrifugation. The organic supernatant is transferred to a polypropylene vial and 1μL is injected into the Waters Acquity® Ultra Performance Liquid Chromatography system coupled with a Waters Acquity® TQ Detector system. Chromatographic separation is achieved on a BEH C The evaluation of the LCMS/MS triazole method showed good precision (intra-assay CVs<6.7%, inter-assay CVs<8.3%). The lower limit of quantitation for all antifungal triazoles tested was 0.10mg/L. Passing Bablok comparisons of voriconazole (n=50) and posaconazole (n=50) showed good correlation with the current HPLC method (Voriconazole LCMS=0.94(HPLC)+0.03, r The rapid pre-analytical s le preparation procedure, short chromatographic time, limit of quantitation and linear range make this LCMS/MS method suitable for determination of plasma voriconazole, posaconazole, itraconazole and hydroxy-itraconazole levels in a high throughput laboratory.
Publisher: Oxford University Press (OUP)
Date: 12-2018
DOI: 10.1373/CLINCHEM.2018.291377
Abstract: Clinical laboratories measure total calcium and adjust for albumin concentrations to predict calcium status. We compared total and adjusted calcium (Adj-Ca) with ionized calcium (Ca2+) for correct assignment of calcium status. The effect of restriction of Adj-Ca reporting in patients with hypoalbuminemia was determined on the basis of frequency of misclassifications. Extraction of laboratory results was performed for 24 months. Adj-Ca was calculated from a modified Payne formula. A further prospective data set for 6 months was collected after stopping reporting of Adj-Ca for patients with an albumin & .0 g/dL. The agreement between Ca2+ and Adj-Ca or total Ca was assessed with Cohen's kappa statistic. In 5553 hospitalized patients, 13604 paired Ca2+ results were analyzed retrospectively. Prospective collection in 1113 paired s les was from 450 patients. Adj-Ca was a poor predictor of calcium status compared to the Ca2+ reference standard in both data sets (agreement 56.9% in the first, 65.6% in the second data set). Renal failure and low albumin concentrations were associated with worse agreement between Adj-Ca and Ca2+. Restriction of reporting of Adj-Ca to albumin concentrations & .0g/dL improved correct classification of calcium status from 65.6% to 77.6% (P & 0.0001). Total Ca performed better than Adj-Ca for low albumin (& .0g/dL) and performed similarly in s les with albumin & .0g/dL. Adj-Ca is unreliable for the classification of calcium status in hospital patients when compared to Ca2+. Adj-Ca overestimates calcium for patients with renal impairment and albumin concentrations & .0g/dL. Restriction of reporting Adj-Ca for albumin below 3.0 g/dL reduces the number of misclassified patients.
Publisher: Wiley
Date: 30-01-2014
DOI: 10.1111/CEN.12392
Abstract: Selenium is effective in improving quality of life and reducing the progression of active Graves' orbitopathy. The effect of correcting relative selenium deficiency on improving Graves' orbitopathy is unknown, as baseline selenium levels have not previously been measured. The study aims to determine whether serum selenium levels are reduced in patients with Graves' disease with orbitopathy (GO) compared with without orbitopathy (GD). A prospective, case-control study performed between 2009 and 2012 at endocrine and ophthalmology clinics in Australia. A total of 198 patients with Graves' disease participated in the study: 101 with Graves' orbitopathy and 97 without Graves' orbitopathy. Serum selenium levels in both groups. Mean serum selenium levels were significantly lower in GO (1·10 ± 0·18 μm) than in GD (1·19 ± 0·20 μm) (P = 0·001). Mean selenium levels appeared to decrease in parallel with increasing severity of GO selenium level was 1·19 ± 0·20 μm in GD, 1·10 ± 0·19 μm in moderate-to-severe GO and 1·09 ± 0·17 μm in sight-threatening GO (P = 0·003). Serum selenium levels remained significantly lower in GO after adjusting for age, smoking status, thyroidectomy, radioactive iodine treatment and residential location. Serum selenium levels are lower in patients with GO compared with GD in an Australian study population with marginal selenium status. Relative selenium deficiency may be an independent risk factor for orbitopathy in patients with Graves' disease.
Publisher: Wiley
Date: 27-03-2007
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2010
DOI: 10.1161/CIRCHEARTFAILURE.109.869438
Abstract: Background— It is often difficult to diagnose heart failure (HF) accurately in patients presenting with dyspnea to the emergency department (ED). This study assessed whether B-type natriuretic peptide (BNP) testing in these patients improved the accuracy of HF diagnosis. Methods and Results— Patients presenting to the Alfred and the Northern Hospital EDs with a chief complaint of dyspnea were enrolled prospectively from August 2005 to April 2007. Patients were randomly allocated to have BNP levels tested or not. The diagnostic gold standard for HF was determined by 1 cardiologist and 1 emergency or respiratory physician who, blinded to the BNP result, independently reviewed all available information. The ED diagnosis of HF in the non-BNP group showed a sensitivity, specificity, and accuracy of 65%, 92%, and 81%, respectively. The BNP group had a similar sensitivity, specificity, and accuracy of 66%, 90%, and 78%, respectively, for the diagnosis of HF in the ED. There was no significant difference between the BNP and non-BNP groups in any of the measures of diagnostic accuracy for HF. Conclusion— In the clinical setting of EDs, availability of BNP levels did not significantly improve the accuracy of a diagnosis of HF. Clinical Trial Registration— clinicaltrials.gov. Identifier: NCT00163709.
Publisher: Wiley
Date: 04-1990
Abstract: To elucidate the biologic relevance of circulating sCT antibodies, an in vitro bioassay system for the detection of neutralizing antibodies was developed utilizing the human breast carcinoma cell line T47D. We reasoned that the inhibition of the dose-dependent cAMP response to sCT in the T47D assay system by anti-sCT antibodies could be used to determine the in vivo relevance of these antibodies. In this report the clinical course of nine patients with Paget's disease of bone treated with intranasal sCT was correlated with the presence of 125I-sCT binding and neutralizing antibodies. Of these seven patients, four were found to have neutralizing antibodies the appearance of the antibodies coincided with the development of resistance. One of these patients was subsequently treated with human calcitonin and revealed a good response to the treatment. There was no clinical resistance observed in the three patients with 125I-sCT binding antibodies but no neutralizing antibodies no resistance was observed in two patients without 125I-sCT binding or neutralizing antibodies. We conclude that this new technique to determine the biologic relevance of circulating anti-sCT antibodies may be an useful adjunct for determining the cause of resistance in patients treated with sCT.
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.IJCARD.2009.12.028
Abstract: Statins are often prescribed for prevention of atherosclerotic outcomes in patients who have chronic heart failure (CHF), if this has an ischaemic etiology. These agents may also possess additional properties, independent of effects on blood lipid levels, which may have an effect on cardiac remodeling. However, beneficial effects were not observed in the recent UNIVERSE trial. We prospectively planned a sub-study of UNIVERSE to explore relevant mechanistic effects of rosuvastatin, including effects on collagen turnover and plasma coenzyme Q10 (CoQ) levels. Additionally, CoQ levels in CHF patients receiving chronic statin therapy were measured. CoQ levels were significantly reduced after 26 weeks of rosuvastatin statin therapy (n = 32), compared to placebo (n = 37) in CHF patients in UNIVERSE trial. Patients with CHF (n = 56) matched for age, gender and severity of disease who had been taking statins for 12 months or longer had CoQ levels of 847 ± 344 nmol/L, significantly lower than 1065.4 ± 394 nmol/L in UNIVERSE patients at baseline (p = 0.0001). Serum types I and III N-terminal procollagen peptide (PINP and PIIINP), measures of collagen turnover which can contribute to cardiac fibrosis were significantly increased in the rosuvastatin group compared to baseline in UNIVERSE patients (PINP: p = 0.03, PIIINP: p = 0.001). In conclusion putative beneficial effects of statin therapy on cardiac remodeling in UNIVERSE may have been negated by increases in collagen turnover markers as well as a reduction in plasma CoQ levels in these patients with CHF.
Publisher: Oxford University Press (OUP)
Date: 04-12-2018
DOI: 10.1093/JBCR/IRX020
Abstract: The place and significance of troponin testing in acute burn injuries has not yet been established. The aims of this study were to determine the incidence and pattern of troponin testing within a large population of acute burn injuries and subsequently to determine the resultant clinical significance of the troponin test results. A retrospective analysis of all patients with acute burn admissions (n = 1,621 patients) to a busy tertiary adult burns center between July 2009 and July 2015. More than a third of our patients had at least one troponin test performed. Men, the elderly, and those with larger burns were more likely to be tested. The majority tested had the laboratory test done within 24 hours of admission. A positive troponin test strongly correlated with increased risk of acute cardiac complication and death, as did burns greater than 15% total body surface area (%TBSA) and age. Acute burns of ≥15% TBSA are associated with elevated troponin levels. Troponins should be tested in those ≥50 years old, with significant burns, and/or premorbid cardiac disease positive results investigated as they affect cardiac and survival outcomes.
Publisher: American Diabetes Association
Date: 03-2004
Publisher: Wiley
Date: 15-08-2005
Publisher: Oxford University Press (OUP)
Date: 07-2018
Abstract: To identify the contents of pills found on an intoxicated patient by ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTof).5 To highlight the potential ability that this technique can add to the clinical laboratory. Illicit PEZ-like pills purchased from an online vendor, containing unknown substances, were investigated by UHPLC-QTof. Accurate mass and experimental data were obtained. Tentative identifications were subsequently confirmed with commercial standards. Accurate mass data, high-energy mass spectra, elucidation software, and a review of the scientific literature enabled the tentative identification of clonazolam and flubromazolam in the PEZ-like pills. On the basis of these tentative identifications, commercial standards were purchased to confirm the initial findings. On subsequent reinterrogation of the data, flubromazolam was identified in the urine specimen of the patient. Utilizing high-resolution mass data, 2 novel benzodiazepines were tentatively identified by reinterrogation of a routine analysis for drugs of abuse. Use of UHPLC-QTof in a clinical toxicology laboratory provides additional capabilities to explain and potentially improve treatment of patients presenting to the emergency department with symptoms possibly due to toxic substance ingestion.
Publisher: Wiley
Date: 05-2006
DOI: 10.1016/J.EJHEART.2005.09.001
Abstract: The determinants of release of brain natriuretic peptide (BNP) in heart failure (HF) are incompletely understood, particularly, the effect of heart rhythm and haemodynamic stress. To investigate the effect of haemodynamic stress on cardiac BNP release in HF and differentiate this response for atrial fibrillation (AF) and sinus rhythm (SR). In 18 HF patients (ejection fraction<40%, 9 in AF and 9 in SR) haemodynamics and BNP levels were measured from arterial and coronary sinus s les at baseline, after 10 min of 20 degrees passive head up tilt (HUT) and after 10 min of isometric handgrip (IHG) exercise. From these data, we calculated a transcardiac BNP gradient and compared results between the AF and SR cohort. During haemodynamic stress in both groups, there were no significance differences in left sided filling pressures. At baseline, there were no differences in BNP measurements between the SR and AF group. The transcardiac BNP gradient increased significantly in the SR (p=0.02) but not the AF cohort, after HUT. During IHG exercise, there was a significant decrease in cardiac BNP release in the AF cohort (p=0.03) but not the SR cohort. These data imply in HF, cardiac rhythm influences cardiac BNP release in response to haemodynamic stress.
Publisher: Elsevier BV
Date: 11-2001
DOI: 10.1016/S0009-8981(01)00676-3
Abstract: Laboratory services for the support of heart and lung transplantation in Australia have adapted to the special needs of the clinicians looking after the heart and lung transplantation patients. Pre-transplantation standardized tests encompassing a wide variety of different parameters are carried out both to establish the suitability of patients for a transplant and to maximize the chance of success following this procedure. Potential solid organ recipients routinely have blood s les sent to a number of centers Australia-wide so that human leukocyte antigen (HLA) presensitization can be checked for at the time a donor becomes available in any state in Australia. Although prospective HLA matching is not performed for thoracic organ transplant recipients, pre-existing antibodies to donor HLA antigens are a contra-indication to transplantation. Following transplantation, the predominant roles of the laboratory are in the monitoring of immunosuppressive drug levels, in the detection of allograft rejection, and in the detection of bacterial infection or viral reactivation. While a number of markers have been proposed in the detection of rejection, we currently rely on interpretation of the histological analysis of biopsies. The treatment with immune suppressive agents, in particular cyclosporin A, has made organ transplantation from non-HLA identical donors possible. As cyclosporin A and other immune suppressive drugs have significant side effects, their concentrations need to be carefully followed to guarantee sufficient immune suppression while avoiding renal failure and other complications including excessive immunosuppression and infectious disease risk. Recently, the role of viral reactivation with the human cytomegalovirus (HCMV) has attained more prominence. HCMV is a potential pathogen in up to 90% of thoracic organ transplant recipients and in the pre-gancyclovir era, it was a major cause of morbidity and mortality in at-risk lung transplant recipients. New PCR-based assays that measure the viral load levels of HCMV allow earlier intervention and more appropriate treatment strategies to prevent the HCMV disease syndromes and optimize the HCMV prophylaxis strategy. Diagnostic pathology testing to support heart and lung transplantation is a combination of routine testing and specialized testing. Depending on the time-critical nature of the tests, this testing has to be done on site or in more centralized testing facilities. Further developments in the laboratory support of heart and lung transplantation will hopefully continue to improve both the short- and long-term outcomes of thoracic organ transplant recipients.
Publisher: Springer Science and Business Media LLC
Date: 06-1989
DOI: 10.1007/BF01718147
Abstract: Memory is believed to depend on activity-dependent changes in the strength of synapses, e.g. long-term potentiation (LTP) and long-term depression (LTD), which can be determined by the sequence of coincident pre- and postsynaptic activity, respectively. It remains unclear, however, whether and how coincident activity of converging efferent pathways can enable LTP and LTD in the pathways simultaneously. Here, we report that, in pentobarbital-anesthetized rats, stimulation (600 pulses, 5 Hz) to Schaffer preceding to commissural pathway within a 40-ms timing window induced similar magnitudes of LTP in both pathways onto synapses of CA1 neurons, with varied LTP magnitudes after reversal of the stimulation sequence. In contrast, in urethane-anesthetized or freely-moving rats, the stimulation to Schaffer preceding to commissural pathway induced Schaffer LTP and commissural LTD simultaneously within a 40-ms timing window, without affecting synaptic efficacy in the reversed stimulation sequence. Coincident activity of Schaffer pathways confirmed the above findings under pentobarbital and urethane anesthesia. Thus, coincident activity of converging afferent pathways tends to switch the pathways to be LTP only or LTP/LTD depending on the activity states of the hippoc us. This network rule strengthens the view that activity-dependent synaptic plasticity may well contribute to memory process of the hippoc al network with flexibility or stability from one state to another.
Publisher: Wiley
Date: 08-01-2018
Abstract: To determine variables that could facilitate safe discharge from the ED following a single high-sensitivity troponin I (HsTnI) result to exclude acute myocardial infarction (AMI). A retrospective cohort study was performed at a tertiary hospital of all patients that had serial HsTnI performed within 12 h of arrival to the ED over a 3 year period. The primary exposure variable of interest was a very low troponin initial result (HsTnI <5 ng/L). Medical record review and risk stratification score calculations were undertaken for all patients with the exposure variable of interest and an abnormal second troponin measurement (HsTnI ≥16 ng/L in women and HsTnI ≥26 ng/L in men). There were 11 970 patients who presented between 1 July 2013 and 30 June 2016 that had serial HsTnI measurements performed. Of these, 4172 (34.9%) patients had an initial HsTnI measurement <5 ng/L. Of the patients with an initial HsTnI <5 ng/L that met inclusion criteria, 56 (1.3%) had a second troponin result above the 99th percentile and 32 (0.8%) cases of non-ST elevation myocardial infarction were diagnosed as well as 15 (0.4%) cases of ST elevation myocardial infarction. There were 44 (93.6%) of all AMI cases that met criteria for high-risk presentations under the National Heart Foundation of Australia guidelines. The negative predictive value of an initial HsTnI <5 ng/L to exclude AMI was 98.9% (95% confidence interval 98.5-99.1). This supports the utilisation of a rapid rule out strategy to exclude AMI for patients that have an initial HsTnI measurement <5 ng/L in conjunction with a robust risk assessment.
Publisher: SAGE Publications
Date: 07-05-2019
Abstract: In critically ill patients, who require multiple blood gas assessments, agreement between arterial and venous blood gas values for pH and partial pressure of carbon dioxide, is not clear. Good agreement would mean that venous values could be used to assess ventilation and metabolic status of patients in intensive care unit. All adult patients admitted to Alfred intensive care unit, Melbourne, from February 2013 to January 2014, who were likely to have arterial and central venous lines for three days, were enrolled. Patients on extra-corporeal life support and pregnant women were excluded. After enrolment, near simultaneous arterial and central venous s ling and analysis were performed at least once per nursing shift till the lines were removed or the patient died. Bland-Altman analysis for repeated measures was performed to assess the agreement between arterio-venous pH and partial pressure of carbon dioxide. A total of 394 paired blood gas analyses were performed from 59 participants. The median (IQR) number of s les per patient was 6 (5–9) with the median (IQR) s ling interval 9.4 (5.2–18.5) h. The mean bias for pH was + 0.036 with 95% limits of agreement ranging from − 0.005 to + 0.078. For partial pressure of carbon dioxide, the values were −2.58 and −10.43 to + 5.27 mmHg, respectively. The arterio-venous agreement for pH in intensive care unit patients appears to be acceptable. However, the agreement for partial pressure of carbon dioxide was poor.
Publisher: Oxford University Press (OUP)
Date: 2010
Publisher: Elsevier BV
Date: 12-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2006
Publisher: Wiley
Date: 10-2018
DOI: 10.1111/AJO.12829
Publisher: Wiley
Date: 22-06-2020
DOI: 10.1002/JPPR.1639
Publisher: Oxford University Press (OUP)
Date: 2005
DOI: 10.1373/CLINCHEM.2004.041103
Abstract: Background: Cardiac damage in coronary artery graft (CABG) surgery is an important contributor to postoperative cardiac dysfunction and delayed hospital discharge. Currently, no simple method exists for its quantification. Methods: In a prospective study of 300 patients having routine CABG surgery, we compared cardiac troponin I (cTnI) concentrations at 6 and 24 h after surgery with electrocardiographic (ECG) results as predictors of an extended postoperative stay in the intensive care unit (ICU) and in the hospital. We stratified outcome variables by tertiles of cTnI concentration and studied the significance of differences between outcome variables across tertiles. Results: Multivariate analysis showed that 24-h cTnI is a significant predictor of increased postoperative ICU stay (P = 0.012) and postoperative hospital stay (P = 0.024). For 6-h cTnI, corresponding significance values were P = 0.29 and 0.9. ECG was of no value (P = 0.39 and 0.47). Differences in 24-h cTnI were highly significant, particularly for lowest vs highest tertiles, and allowed stratification of risk into “low” (& μg/L), “equivocal” (10–20 μg/L), and “high” (& μg/L). Conclusions: Use of a single 24-h cTnI value to quantify perioperative myocardial damage identifies patients who are at greater risk of extended ICU and hospital stays. This strategy could assist in allocation of patients to different management streams after CABG surgery.
Publisher: Wiley
Date: 09-2008
DOI: 10.1002/J.2055-2335.2008.TB00835.X
Abstract: To quantify the uptake of thiopurine methyltransferase (TPMT) phenotyping in patients on thiopurines. A retrospective audit was undertaken to identify all patients initiated on thiopurines from 1 August 2003 to 31 May 2006 at a tertiary referral hospital. All patients dispensed azathioprine, mercaptopurine and thioguanine were identified from computerised dispensing records. TPMT phenotype test results were obtained from the hospital's pathology service for the period 1 July 2003 to 30 June 2006. Of the 287 patients initiated on thiopurines, 21 (8.8%) had TPMT activity measured. Thiopurines were widely prescribed across a number of medical disciplines with the largest usage in the transplant units − 88 lung transplant recipients and 3 dual heart and lung transplant recipients. Only one transplant recipient had TPMT activity measured. In the dermatology unit, 47% of patients receiving thiopurines underwent TPMT phenotyping. The uptake of TPMT phenotyping in patients on thiopurines was low and variable depending on the clinical unit. Further efforts to increase the uptake of TPMT phenotyping before initiation of thiopurine therapy are warranted.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.IJCARD.2008.10.022
Abstract: We conducted a prospective, randomised, open-label, blinded end point (PROBE) study examining the relative efficacy of irbesartan 300 mg/day versus maximising dose of ACE inhibitor, additional to background conventional heart failure therapy. Patients with CHF, NYHA Class II-III and a left ventricular ejection fraction 0.05). This PROBE study has demonstrated similar clinical responses with increased dose of ACE inhibitor compared to addition of ARB in patients with systolic CHF. These findings suggest that either approach to increasing renin-angiotensin blockade in patients taking low doses of background ACE inhibitor results in similar clinical outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-07-2016
Abstract: Macrophage migration inhibitory factor ( MIF ) is a key regulator of inflammatory responses, including in the heart. Plasma MIF is elevated early in the course of acute myocardial infarction. In this study, we hypothesized that plasma MIF may also be increased in acute myocardial ischemia. Patients undergoing cardiac stress test (stress nuclear myocardial perfusion scan or stress echocardiography) were recruited. Twenty‐two patients had a stress test indicative of myocardial ischemia and were compared with 62 patients who had a negative stress test. Plasma MIF was measured by ELISA before and after the stress test. MIF was also measured in patients with peripheral arterial occlusive disease before and after exercise causing claudication. Gene and protein expression of MIF was measured in mouse cardiac and skeletal muscle tissue by real‐time polymerase chain reaction and western blot, respectively. Plasma MIF was elevated at 5 and 15 minutes after stress (relative to before stress) in patients with a positive test, compared with those with a negative test. In contrast, high‐sensitivity troponin T and C‐reactive protein were not altered after stress in either group. MIF was not altered after exercise in PAOD patients, despite the occurrence of claudication, suggesting that plasma MIF is not a marker for skeletal muscle ischemia. This may be explained by a lower gene and protein expression of MIF in skeletal muscle than the heart. Our results suggest that plasma MIF is an early marker for acute myocardial ischemia.
Publisher: AMPCo
Date: 08-2012
DOI: 10.5694/MJA12.10988
Abstract: For many years, the diagnosis of diabetes has been made through the laboratory-based measurement of fasting or random blood glucose levels, or using the oral glucose tolerance test. A glycated haemoglobin (HbA(1c)) level ≥ 6.5% (48 mmol/mol) is now also acceptable for diagnosing diabetes. Caution is needed in interpreting HbA(1c) test results in the presence of conditions affecting red blood cells or their survival time, such as haemoglobinopathies or anaemia.
Publisher: Elsevier BV
Date: 02-2012
Publisher: Wiley
Date: 1991
Abstract: Parathyroid hormone-related protein (PTHrP) plays a major role in the syndrome of humoral hypercalcemia of malignancy (HHM) by its actions on bone and kidney. In this study an isolated osteoclast bone resorption assay was used to investigate the actions of this peptide and the structure-activity relationships for its resorption effect. As with PTH, neither synthetic nor recombinant PTHrP preparations stimulated resorption within highly purified osteoclast populations. Resorption was stimulated only in the presence of contaminating osteoblasts or in cocultures with the osteoblast-like cell line UMR-106. In the presence of osteoblasts PTHrP-(1-34) and PTHrP-(1-84) stimulated bone resorption in a dose-dependent manner with a potency comparable to that of PTH-(1-34) on a molar basis. The biologic activity of the PTHrP was shown to reside in the first 34 amino acids, and within that region the structural requirements for promotion of osteoclastic resorption resembled closely those for promotion of cyclic AMP formation in osteoblast-like cells. Using emulsion autoradiography with iodinated PTHrP-(1-34) and PTHrP-(1-84) on mixed bone cell preparations from neonatal rats, specific binding was demonstrated only to osteoblasts, not to osteoclasts. These results clearly demonstrate that PTHrP is a potent stimulator of bone resorption and that these effects are, like those of PTH, mediated by initial actions upon cells of the osteoblast lineage.
Publisher: AMPCo
Date: 11-2011
DOI: 10.5694/MJA11.11131
Publisher: Oxford University Press (OUP)
Date: 06-2016
DOI: 10.1373/CLINCHEM.2015.252569
Abstract: High-sensitivity cardiac troponin I (hs-cTnI) assays show sex-dependent differences in the 99th percentile of healthy populations, with concentrations in women approximately 50% lower. The adoption of sex-specific cutoffs seems appropriate, although it is not yet clear what effect these will have on acute myocardial infarction (AMI) diagnosis and management. We conducted a retrospective pre- and postchangeover analysis of troponin I testing in the 6 months before and after moving from the contemporary Abbott Architect TnI assay (cTnI) to hs-cTnI at 2 tertiary centers in Australia and New Zealand. The cTnI cutoff was 30 ng/L for both sexes, whereas a female-specific cutoff of 16 ng/L was adopted upon changeover to hsTnI. Changeover from the cTnI assay to the hs-cTnI assay increased the number of female patients with increased troponin I concentrations at both sites (from 29.7% to 34.9% and from 22.4% to 30.8% P & 0.001). There was no statistically significant change in the number of men with increased concentrations in the same time period (P = 0.09). The increased percentage of women with increased troponin I was not associated with an increase in the number of women with AMI diagnoses at either center. Angiographic data available from 1 center showed no change in the percentage of angiograms performed in women. Although increasing the proportion of women with increased troponin I, adopting sex-specific cutoffs with the hs-cTnI assay did not lead to an increase in AMI diagnoses in females, or in the number of women undergoing angiography.
Publisher: Oxford University Press (OUP)
Date: 02-2006
DOI: 10.1373/CLINCHEM.2005.057216
Abstract: Background: Cardiac troponins are specific biochemical markers of myocardial injury used in the diagnosis of acute myocardial disease and cardiac risk stratification. To avoid misclassification of patients, troponin assays must demonstrate precision at the low end of the measuring range. We report our evaluation of the Architect STAT Troponin-I assay (Abbott Diagnostics), comparison of low-positive results with 2 other assays, and occurrence of heterophile antibody interference in the assay. Methods: We assessed analytical performance on the ci8200 according to CLSI protocols, using quality-control and patient s les. Our healthy reference population included 480 blood donors. For correlation studies against the AxSYM first-generation cTnI (Abbott Diagnostics) and Access second-generation AccuTnI (Beckman Coulter) assays, we used 339 s les from hospital patients. Results: The CV of the Architect STAT Troponin-I assay was 10% near the 99th percentile for the reference population (0.03 μg/L). Comparison with the AxSYM first-generation cTnI assay showed good correlation at higher concentrations, but better sensitivity of the Architect cTnI assay at low concentrations, which were clinically relevant as shown by review of patient histories. Correlation was good at the low end of the measuring range with the Access second-generation AccuTnI. Over the last 12 months we have identified 6 patients with heterophile antibodies causing positive interference. Conclusions: The Architect STAT Troponin-I assay provides highly sensitive measurement of cTnI with a CV of 10% near the upper limit of a reference population however, heterophile antibodies can interfere with this assay.
Publisher: Walter de Gruyter GmbH
Date: 08-08-2018
Abstract: There are a variety of initial laboratory tests or combinations of tests that can be performed when a monoclonal gammopathy is suspected including serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), serum immunofixation (IFE) and serum free light chain assays. Some groups have recently used simplified “screening” IFE methods for the detection of monoclonal gammopathies leveraging the greater sensitivity of IFE over SPEP alone to improve the detection of monoclonal gammopathies. These screening techniques have been predominantly evaluated against lower resolution agarose gel electrophoresis techniques. In this study we evaluated the diagnostic performance of the combined κ and λ light chain screening immunofixation (CLIF) in comparison to serum protein electrophoresis on a high-resolution (Sebia Hydragel 15 HR) agarose gel system. Each gel was interpreted by three adjudicators. A total of 156 patient s les were analysed. Adjudicated diagnoses based on the screening techniques were compared against the results of high resolution serum protein electrophoresis and high resolution standard immunofixation performed during routine laboratory operation. Where standard immunofixation was not performed a combination of a review of medical records, serum free light chains, UPEP and bone marrow aspirate and trephine and subsequent standard immunofixation and protein electrophoresis results where available were used to confirm the absence of a monoclonal gammopathy. In this cohort a total of 65 (41%) patients had a paraprotein confirmed by standard immunofixation. HR SPEP had a sensitivity and specificity of 95% and 85%, respectively, while CLIF had a sensitivity and specificity of 88% and 97%, respectively. Overall we found that high-resolution gel serum protein electrophoresis using a Sebia Hydragel 15 HR system was more sensitive than a screening immunofixation method (CLIF) for the detection of paraproteins in patient serum in this patient cohort. The drawback of the greater sensitivity of HR SPEP was a higher false positive rate requiring an increased utilisation of follow up immunofixation electrophoresis.
Publisher: American College of Physicians
Date: 07-2023
DOI: 10.7326/M23-0675
Publisher: Massachusetts Medical Society
Date: 24-02-2005
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.PATHOL.2018.03.006
Abstract: Cocaine use in Australia is increasing, with approximately 2.5% of the surveyed population having used cocaine. In the USA, levamisole, a widely used anti-helminthic veterinary drug has been increasingly detected as a cutting agent in cocaine seizures. Levamisole is known to cause agranulocytosis in humans. We ascertained the prevalence of levamisole-adulterated cocaine, detectable in the urine from patients that had undergone a pathology request for a urine drug screen. We assayed routinely requested urines that were positive for cocaine on immunoassay with liquid chromatography high resolution quadrupole time of flight mass spectrometry (LC-QToF). We investigated available urine s les from a period of 2 years that had a positive result for cocaine. In addition, we examined s les that were below the cut-off for cocaine on immunoassay. Specimens were analysed for the presence of levamisole and other 'unknown' drugs. In the period under investigation the laboratory examined 3665 urine s les for cocaine: 1.4% (n = 51) of the s les were positive for cocaine by immunoassay and half of these (n = 26, 51%) were further examined by LC-QToF. In addition, we examined 10 s les that were negative by immunoassay (as defined by AS/NZS 4308:2008). Levamisole was detected in the urine of cocaine users in approximately 75% of cases. Other illicit drugs were also frequently found in this cohort. The most common illicit drugs detected were meth hetamine, ecstasy and cannabis. Australian cocaine is widely adulterated with levamisole. Cocaine users are at risk of levamisole related health problems in addition to the problems related to cocaine.
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.CLINBIOCHEM.2017.01.008
Abstract: There has been limited examination of the performance of glomerular filtration rate estimation (eGFR) equations in lung transplant populations. This study aimed to compare the performance of serum creatinine and cystatin C based eGFR equations with Tc-99m diethylenetriaminepentaacetic acid (DTPA) GFR measurements in in iduals with end-stage lung disease, either prior to, or following, lung transplantation. In this prospective observational study, participants underwent GFR measurements with Tc-99m Pentetate. Measured results were compared with GFR estimates derived from estimation equations [4-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine, cystatin C and creatinine-cystatin C combined equations]. Ninety-seven in iduals were studied (77 post- and 20 wait-listed for transplantation). Median (range) radionucleotide GFR was 56.7ml/min/1.73m This study shows adequate predictive ability of CKD-EPI creatinine in the cohort as a whole, but unacceptable performance in patients with cystic fibrosis, low arm muscle mass and/or low body mass index. Our findings demonstrate that cystatin C may be a preferable filtration marker in these subgroups.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.PATHOL.2019.11.002
Abstract: Waldenström macroglobulinaemia (WM) is an indolent non-Hodgkin lymphoma which usually presents with symptoms related to infiltration of bone marrow or other tissues like lymph nodes, liver or spleen and has certain unusual clinical manifestations, e.g., renal and central nervous system (CNS) involvement. It also has an array of laboratory features including hypersecretion of IgM, cryoglobulinaemia, increased plasma viscosity and identification of mutated MYD88
Publisher: Australasian Association for Clinical Biochemistry and Laboratory Medicine
Date: 2021
Publisher: Wiley
Date: 22-06-2021
DOI: 10.1111/NEP.13910
Abstract: Albumin‐adjusted calcium remains widely used in clinical practice with guidelines for chronic kidney disease (CKD) mineral bone disorder recommending the use of serum calcium for monitoring. This is despite ionized calcium being the biologically active fraction. This study aimed to investigate the ability of total calcium and albumin‐adjusted calcium to correctly assign calcium status in stage 5/5D CKD across non‐dialysis, haemodialysis and peritoneal dialysis patients. Over a 6‐months, 352 paired serum and ionized calcium s les were collected from stage 5 ( n = 58) and 5D ( n = 294, 196 haemodialysis, 98 peritoneal dialysis) CKD patients in a tertiary‐hospital setting. Albumin‐adjusted calcium was calculated using the modified‐Payne formula. Ionized calcium was the reference standard. The agreement between the two methods in assigning calcium status was assessed using Cohen's weighted kappa (κ) statistic. Albumin‐adjusted calcium was a poor predictor of calcium status compared to ionized calcium in stage 5/5D CKD (observed agreement 0.42, weighted κ 0.20, 95% CI 0.15–0.26). Dialysis dependence was associated with worse agreement (observed agreement 0.38, weighted κ 0.14, 95% CI 0.09–0.19). Total calcium was more reliable, however, remained inaccurate. Calcium status was not more accurately classified in those with higher albumin levels ≥30 g/L (observed agreement 0.47, weighted κ 0.23, 95% CI 0.10–0.36). Total calcium provides better approximation of calcium status than albumin‐adjusted calcium in stage 5/5D CKD. Albumin‐adjusted calcium tends to ‘overcorrect’ serum calcium upward. Clinicians should use ionized calcium where accurate measure of calcium is indicated, with total calcium used as the next best option where resources are limited.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Wiley
Date: 10-1998
DOI: 10.1359/JBMR.1998.13.10.1640
Abstract: Multiple myeloma frequently leads to complications, such as osteolytic lesions, hypercalcemia, and pathological fractures. Increased bone resorption in myeloma is due to osteoclast activation. The nature of the osteoclast activator(s) remains unclear. We describe a case of multiple myeloma with marked hypercalcemia and skeletal complications that progressed rapidly despite chemotherapy. The patient had marked hypercalcemia at diagnosis (4.5 mmol/l), and elevated parathyroid hormone-related protein (PTHrP) levels were found in plasma. Analysis of the bone marrow trephine biopsy showed PTHrP gene transcription and protein in myeloma cells. These results provide strong evidence for the production of significant amounts of PTHrP by human myeloma cells. PTHrP has been measured as elevated in the plasma of patients with myeloma and might be an important contributor to the skeletal complications in this disease.
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.JVS.2019.02.041
Abstract: The cause of perioperative myocardial infarction (PMI) is postulated to involve hemodynamic stress or coronary plaque destabilization. We aimed to evaluate perioperative factors in patients with peripheral artery disease (PAD) undergoing major vascular surgery to determine the likely mechanisms and predictors of PMI. This was a prospective cohort study of 133 patients undergoing major vascular surgery including open abdominal aortic aneurysm (AAA) repair (n = 40) and major suprainguinal or infrainguinal arterial bypasses (non-AAA n = 93). Preoperative assessment with history, physical examination, and peripheral artery tonometry was performed in addition to plasma s ling of biomarkers associated with inflammation and coronary plaque instability. The primary outcome was occurrence of a 30-day cardiovascular event (CVE composite of PMI [troponin I elevation >99th percentile reference of ≥0.1 μg/L], stroke, or death). Of 133 patients, 36 patients (27%) developed a 30-day CVE after vascular surgery, and all were PMI. Patients with 30-day CVE were older (75 ± 8 years vs 69 ± 10 years, mean ± standard deviation P = .001), had higher prevalence of hypertension (94% vs 79% P = .01) and preoperative beta-blocker therapy (50% vs 29% P = .02), and had longer duration of surgery (5.1 ± 1.8 hours vs 4.0 ± 1.1 hours P < .0001). Significant elevations in cystatin C, N-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin I, high-sensitivity troponin T, matrix metalloproteinase 3, and osteoprotegerin occurred in those who developed 30-day CVE (all P < .05). Multivariate binary logistic regression identified AAA surgery and log-transformed NT-proBNP to be independent preoperative predictors of 30-day CVE (area under the receiver operating characteristic curve = 0.81). In patients with peripheral artery disease undergoing major vascular surgery, the likely mechanism of PMI appears to be the hemodynamic stress related to the type and duration of surgery. NT-proBNP was a useful independent predictor of CVE and thus may serve as an important biomarker of cardiovascular fitness for surgery.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-09-2013
Abstract: Early diagnosis and knowledge of infarct size is critical for the management of acute myocardial infarction ( MI ). We evaluated whether early elevated plasma level of macrophage migration inhibitory factor ( MIF ) is useful for these purposes in patients with ST ‐elevation MI ( STEMI ). We first studied MIF level in plasma and the myocardium in mice and determined infarct size. MI for 15 or 60 minutes resulted in 2.5‐fold increase over control values in plasma MIF levels while MIF content in the ischemic myocardium reduced by 50% and plasma MIF levels correlated with myocardium‐at‐risk and infarct size at both time‐points ( P .01). In patients with STEMI , we obtained admission plasma s les and measured MIF , conventional troponins ( TnI , TnT ), high sensitive TnI ( hsTnI ), creatine kinase ( CK ), CK ‐ MB , and myoglobin. Infarct size was assessed by cardiac magnetic resonance ( CMR ) imaging. Patients with chronic stable angina and healthy volunteers were studied as controls. Of 374 STEMI patients, 68% had elevated admission MIF levels above the highest value in healthy controls ( .6 ng/mL), a proportion similar to hsTnI (75%) and TnI (50%), but greater than other biomarkers studied (20% to 31%, all P .05 versus MIF ). Only admission MIF levels correlated with CMR ‐derived infarct size, ventricular volumes and ejection fraction (n=42, r=0.46 to 0.77, all P .01) at 3 day and 3 months post‐ MI . Plasma MIF levels are elevated in a high proportion of STEMI patients at the first obtainable s le and these levels are predictive of final infarct size and the extent of cardiac remodeling.
Publisher: Wiley
Date: 11-01-2013
Abstract: To estimate the ability of commonly measured laboratory variables to predict imminent (within the same or next calendar day) medical emergency team (MET) calls, ICU admission or death. We performed a retrospective observational study of ED patients. We estimated the ability of each laboratory variable or combination of variables together with patient age to predict imminent MET calls, ICU admission or death. We externally validated our findings in patients from a different hospital. We studied 160 341 batches in 71 453 ED patients (average age: 59.9 ± 22.1 years) for a total of 1 million in idual measurements. There were 341 MET calls, 160 ICU admissions from the wards and 858 deaths. Multivariable modelling achieved a receiver operating characteristic area under the curve (ROC-AUC) of 0.69 (95% CI 0.63-0.74) for imminent MET call with prediction occurring a mean of 11.9 h before the call. Additionally, it achieved a ROC-AUC of 0.82 (95% CI 0.73-0.87) for imminent ICU admission. Finally, it achieved a ROC-AUC of 0.90 (95% CI 0.87-0.91) for imminent death. When tested using an additional 37 367 batches from a cohort of 21 430 ED patients from a second teaching hospital, the multivariate model achieved a ROC-AUC of 0.70 (95% CI 0.66-0.73) for imminent MET call, a ROC-AUC of 0.84 (95% CI 0.78-0.90) for imminent ICU admission. Finally, it achieved a ROC-AUC of 0.89 (95% CI 0.86-0.91) for imminent death. Commonly performed laboratory tests can help predict imminent MET calls, ICU admission or death in ED patients. Prospective investigations of the clinical utility of such predictions appear desirable.
No related grants have been discovered for Hans Schneider.