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Davis W.A.,University of Western Australia | Beilby J.,PathWest | Davis T.M.E.,University of Western Australia
Diabetic Medicine | Year: 2011

Aims To determine whether the reduction in urinary albumin excretion through renin-angiotensin-aldosterone system blockade found in intervention trials extends to community-based patients with Type2 diabetes. Methods We analysed data from 302 participants in the longitudinal observational Fremantle Diabetes Study who commenced angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy during follow-up and who had an annual assessment on either side of this therapeutic change. Results At baseline, the patients had a mean age of 63.8years, a median diabetes duration of 4years, a median HbA 1c of 7.6% (60mmol/mol) and a geometric mean (sd range) urinary albumin:creatinine ratio of 3.3mg/mmol (0.8-13.1mg/mmol). The percentages with normo-, micro- and macroalbuminuria were 49.0, 38.4 and 12.6%, respectively. During 6.1±1.7years of follow-up, initiation of renin-angiotensin-aldosterone system blockade was associated with a larger geometric mean (sd range) absolute albumin:creatinine ratio reduction in the patients with macroalbuminuria compared with those who had either normo- or microalbuminuria [-40.9(-825.7 to 159.9)mg/mmol) vs. 1.7(-1.6 to 20.0)mg/mmol and -0.5(-23.0 to 39.5)mg/mmol, respectively; P<0.001]. These changes remained significant after adjustment for changes in blood pressure and other potentially confounding variables, including drug dose and angiotensin-converting enzyme genotype. The post-treatment median albumin:creatinine ratios were 35.4 and 27.4% lower than before treatment in those with micro- or macroalbuminuria, respectively. Conclusions Usual-care initiation of renin-angiotensin-aldosterone system blockade confers a quantitatively similar renal benefit to that in intervention trials in Type2 diabetes. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

McKinnon E.J.,Murdoch University | Rossi E.,PathWest | Beilby J.P.,PathWest | Beilby J.P.,University of Western Australia | And 5 more authors.
Clinical Gastroenterology and Hepatology | Year: 2014

Background & Aims: Serum levels of ferritin are commonly measured to assess iron stores but are affected by factors such as obesity and chronic disease. Published reference ranges have not changed in decades, and the number of patients whose levels exceed the upper limits has been increasing. As a result, more patients are evaluated for iron overload. Methods: We compared serum levels of ferritin in 1188 Australian adults who participated in the 2005 Busselton Population Survey with levels from the 1995 survey. Parametric regression was used to assess the effects of body weight and biochemical parameters on serum level of ferritin to derive contemporary population-appropriate reference ranges. Results: In 2005, age-adjusted levels of ferritin were 21% higher in men (P < .0001) and 10% higher in women (P= .01) than in 1995; 31% of men exceeded levels of 300 μg/L, compared with 23% in 1995. Body mass index (BMI) ≥25 kg/m2 was associated with higher levels of ferritin in men ≥35 years old and in postmenopausal women (P ≤ .002). Serum level of γ-glutamyltransferase (GGT) correlated with serum level of ferritin (P < .0001). In men, the estimated 95th percentiles ranged from 353 to 495 μg/L (<35 years), from 350 to 511 μg/L (≥35 years, BMI <25 kg/m2), and from 413 to 696 μg/L (≥35 years, BMI ≥25 kg/m2) when GGT levels were 10-75 IU/L. In women, the 95th percentiles ranged from 106 to 235 μg/L (premenopausal), from 222 to 323 μg/L (postmenopausal, BMI <25 kg/m2), and from 249 to 422 μg/L (postmenopausal, BMI ≥25 kg/m2) when GGT levels were 8-45 IU/L. Conclusion: Serum levels of ferritin increased significantly between 1995 and 2005. Reference ranges that accommodate demographic and biomedical variations will assist clinicians in identifying individuals who require further evaluation for iron overload. © 2014 AGA Institute.

Nowak A.K.,University of Western Australia | Nowak A.K.,Sir Charles Gairdner Hospital | Nowak A.K.,Western Research Institute | Francis R.J.,Positron | And 17 more authors.
Clinical Cancer Research | Year: 2010

Purpose: Existing prognostic systems for malignant pleural mesothelioma do not incorporate imaging information. We aimed to identify the contribution of quantitative fluorodeoxyglucose positron emission tomography (FDG-PET) analysis to other prognostic variables in this disease. Experimental Design: Patients with malignant pleural mesothelioma underwent helical thoracoabdomin0al computed tomography and FDG-PET scans at baseline. Patients were treated as clinically indicated and followed for survival. FDG-PET variables derived included total glycolytic volume, a composite of tumor volume and glycolytic activity. Results: Ninety-three patients were accrued from 2003 to 2006. Of 89 eligible assessable patients, 28 had undergone pleurodesis before enrolment. Seventeen patients remained alive at analysis; median survival is 15.4 months. On univariate analysis, significant prognostic factors were: total glycolytic volume on FDG-PET (P = 0.003), sarcomatoid histology (P < 0.0005), weight loss (P = 0.031), computed tomography stage (P = 0.015), and European Organization for Research and Treatment of Cancer good prognostic score (P = 0.049). In patients with epithelioid or biphasic histology, baseline total glycolytic volume remained predictive of survival in patients with (P = 0.01) or without (P = 0.018) previous pleurodesis. In multivariate analysis, no variable other than histology contributed to the model in patients with sarcomatoid histology; total glycolytic volume and weight loss contributed to the models in patients with nonsarcomatoid histology. computed tomography-assessed tumor-node-metastasis stage did not contribute to the model. A nomogram, which incorporates quantitative PET parameters and pleurodesis into prognostic information, is presented. Conclusions: Sarcomatoid histology remains the strongest prognostic factor. In patients with non sarcomatoid disease, volumetric FDG-PET parameters are more predictive of survival than tumor-node-metastasis staging, suggesting that tumor volume and glycolytic activity may be more important determinants of prognosis in malignant pleural mesothelioma than anatomic extent of disease. ©2010 AACR.

Nowak A.K.,Sir Charles Gairdner Hospital | Nowak A.K.,University of Western Australia | Nowak A.K.,National Center for Asbestos Related Diseases | Millward M.J.,Sir Charles Gairdner Hospital | And 19 more authors.
Journal of Thoracic Oncology | Year: 2012

INTRODUCTION:: There is no accepted second-line therapy for patients with advanced malignant pleural mesothelioma (MPM), whose disease has progressed after first-line chemotherapy. The multitargeted tyrosine kinase inhibitor sunitinib malate targets several pathways overexpressed in mesothelioma. This phase II study assessed objective response to sunitinib and correlative biomarkers in patients with progressive pretreated MPM. METHODS:: Eligible patients had confirmed MPM, radiological progression after chemotherapy, Eastern Cooperative Oncology Group performance status 0 to 1, and measurable disease. Patients received oral sunitinib 50 mg daily for 28 of every 42 days. The primary endpoint was objective radiological response. Patients without prior pleurodesis had fluorodeoxyglucose positron emission tomographic response assessed by total glycolytic volume criteria. Correlative biomarkers included serum mesothelin, vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, sVEGFR-2, sVEGFR-3, and s-kit. RESULTS:: Fifty-three patients received sunitinib between July 2006 and December 2009; 51 were assessable for response. Patients received a median of two cycles (range, 1-12); 40% required dose reduction. Fatigue was the most prominent toxicity. Six patients (12%) had a confirmed radiological partial response, 34 (65%) had stable disease, and 11 (22%) had progressive disease as best response. Six of 20 patients had a decrease in fluorodeoxyglucose positron emission tomographic total glycolytic volume of 15% or more. Median overall survival was 6.1 months, and median time to progression was 3.5 months. Correlative biomarkers did not predict treatment response. CONCLUSIONS:: Sunitinib has activity in a subset of patients with pretreated MPM. Consideration should be given to different treatment schedules and examination of other biomarkers for further study of sunitinib in MPM. © 2012 by the International Association for the Study of Lung.

Kennedy B.F.,University of Western Australia | McLaughlin R.A.,University of Western Australia | Kennedy K.M.,University of Western Australia | Chin L.,University of Western Australia | And 8 more authors.
Cancer Research | Year: 2015

An accurate intraoperative identification of malignant tissue is a challenge in the surgical management of breast cancer. Imaging techniques that help address this challenge could contribute to more complete and accurate tumor excision, and thereby help reduce the current high reexcision rates without resorting to the removal of excess healthy tissue. Optical coherence microelastography (OCME) is a three-dimensional, high-resolution imaging technique that is sensitive to microscale variations of the mechanical properties of tissue. As the tumor modifies the mechanical properties of breast tissue, OCME has the potential to identify, on the microscale, involved regions of fresh, unstained tissue. OCME is based on the use of optical coherence tomography (OCT) to measure tissue deformation in response to applied mechanical compression. In this feasibility study on 58 ex vivo samples from patients undergoing mastectomy or wide local excision, we demonstrate the performance of OCME as a means to visualize tissue microarchitecture in benign and malignant human breast tissues. Through a comparison with corresponding histology and OCT images, OCME is shown to enable ready visualization of features such as ducts, lobules, microcysts, blood vessels, and arterioles and to identify invasive tumor through distinctive patterns in OCME images, often with enhanced contrast compared with OCT. These results lay the foundation for future intraoperative studies. Cancer Res; 75(16); 3236-45. © 2015 AACR.

Kennedy B.F.,University of Western Australia | Mclaughlin R.A.,University of Western Australia | Kennedy K.M.,University of Western Australia | Chin L.,University of Western Australia | And 5 more authors.
Biomedical Optics Express | Year: 2014

We present optical coherence micro-elastography, an improved form of compression optical coherence elastography. We demonstrate the capacity of this technique to produce en face images, closely corresponding with histology, that reveal micro-scale mechanical contrast in human breast and lymph node tissues. We use phase-sensitive, three-dimensional optical coherence tomography (OCT) to probe the nanometer-to-micrometer-scale axial displacements in tissues induced by compressive loading. Optical coherence micro- elastography incorporates common-path interferometry, weighted averaging of the complex OCT signal and weighted least-squares regression. Using three-dimensional phase unwrapping, we have increased the maximum detectable strain eleven-fold over no unwrapping and the minimum detectable strain is 2.6 με. We demonstrate the potential of mechanical over optical contrast for visualizing micro-scale tissue structures in human breast cancer pathology and lymph node morphology. © 2014 Optical Society of America.

Sinclair L.,Sullivan Nicolaides Pathology | Sinclair L.,Bond University | Hall S.,PathWest | Badrick T.,Bond University
Pathology | Year: 2014

This study was designed to create a snapshot of Australian haematology reference intervals (RIs) in use, in particular red cell parameters. We present an analysis of survey results conducted across Australian laboratories between November 2012 and January 2013. All Australian laboratories enrolled in the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP) were invited to participate in the December 2012 Survey Monkey survey, with a response from 85 laboratories (17%) received. The scope included laboratory demographics (location, size/throughput, and network), RIs in use for the full blood count and selected derived parameters, their frequency of revision, source and statistical approach for derivation. Further questions related to uncertainty of measurement, pregnancy values, paediatric/adult cut-off, haematology profiles reported and the use of extended parameters. There is more consistency with some upper and lower limits than others, and wide ranges for reported uncertainty of measurement (UM). There is no apparent consistency with RIs used for particular instruments and technologies. When laboratories change their RIs, most obtain them from a text book, paper or another laboratory and have difficulty in determining the source. If they do determine their own, most don't have a standard operating procedure and calculations are not consistent in terms of sample size and statistical methods used. We have presented evidence of the wide variations in RIs used in Australian laboratories and that arguably these do not differ significantly from each other. The paediatric age cut-off requires standardisation. © 2014 Royal College of Pathologists of Australasia.

Mackie K.E.,University of Western Australia | Zhou Z.,University of Western Australia | Robbins P.,PathWest | Bulsara M.,The University of Notre Dame Australia | Zheng M.H.,University of Western Australia
Journal of Bone and Joint Surgery - Series A | Year: 2011

Background: Although total hip arthroplasty is one of the most common orthopaedic surgical procedures, it remains unclear whether histopathological examination of the excised femoral head adds to the quality of patient care. We propose that assessment of femoral heads resected during total hip arthroplasty and donated for allograft use may provide a profile of femoral head pathology that benefits total hip arthroplasty patients and bone donors. Methods: We retrospectively analyzed the histological findings reported for 6161 femoral heads donated for allograft use between 1993 and 2006. Specimens obtained during total hip arthroplasty and specimens donated at death were reviewed. Follow-up investigations that resulted from abnormal histopathological findings were also reviewed. The Western Australian Cancer Registry was used to determine whether patients with a suspected neoplasm were subsequently diagnosed with such a disease. A retrospective review of the histopathological findings was conducted to evaluate and reclassify all previous observations of abnormalities. Results: One hundred and five femoral heads demonstrated abnormal or reactive histopathological features not reported prior to surgery and were rejected for allograft use. A reactive lymphocytic infiltrate, most likely due to osteoarthritis, was the most commonly identified feature (forty-five cases). Other features observed in twenty-seven cases were also most likely due to the presence of severe osteoarthritis. Ten femoral heads demonstrated plasmacytosis, which may have been related to osteoarthritis. Two patients were diagnosed with Paget's disease, and two, with rheumatoid arthritis. Nineteen patients had a suspected neoplasm. Of these nineteen, eight cases of non-Hodgkin's lymphoma or chronic lymphocytic leukemia and one case of myelodysplastic syndrome were confirmed on further investigation. One subsequently confirmed malignancy was detected per 770 femoral heads examined. Conclusions: Our findings indicate that, even with a detailed medical history and careful physical examination, clinically important diseases including neoplasms and Paget's disease are observed in patients diagnosed with osteoarthritis prior to total hip arthroplasty. Histological examination plays an integral role in quality assurance in femoral head banking, and it also represents a possible early diagnostic test for bone and bone-marrow-related diseases in patients undergoing total hip arthroplasty. Copyright © 2011 by The Journal of Bone and Joint Surgery, Incorporated.

Ramakonar H.H.,Sir Charles Gairdner Hospital | Thomas A.,Pathwest | Lind C.R.P.,Sir Charles Gairdner Hospital | Lind C.R.P.,University of Western Australia
Journal of Clinical Neuroscience | Year: 2011

Intramedullary spinal cord metastasis to the conus medullaris is very rare. We report a 44-year-old woman with an intra-axial conus medullaris metastasis from periurethral adenocarcinoma. To our knowledge, this is the first report in the literature. We also discuss the clinical features, possible pathophysiological mechanisms and treatment options for intramedullary spinal cord metastasis to the conus medullaris. © 2010 Elsevier Ltd. All rights reserved.

PubMed | PathWest and University of Western Australia
Type: Journal Article | Journal: Journal of biomedical optics | Year: 2013

Optical coherence elastography (OCE) is an emerging imaging technique that probes microscale mechanical contrast in tissues with the potential to differentiate healthy and malignant tissues. However, conventional OCE techniques are limited to imaging the first 1 to 2 mm of tissue in depth. We demonstrate, for the first time, OCE measurements deep within human tissues using needle OCE, extending the potential of OCE as a surgical guidance tool. We use needle OCE to detect tissue interfaces based on mechanical contrast in both normal and malignant breast tissues in freshly excised human mastectomy samples, as validated against histopathology. Further, we demonstrate the feasibility of in situ measurements >4 cm from the tissue surface using ultrasound guidance of the OCE needle probe. With further refinement, our method may potentially aid in accurate detection of the boundary of the tumor to help ensure full removal of all malignant tissues, which is critical to the success of breast-conserving surgery.

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