Chemical Pathology

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Chemical Pathology

Brisbane, Australia
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Martin S.A.,University of Adelaide | Atlantis E.,University of Western Sydney | Lange K.,University of Adelaide | Taylor A.W.,University of Adelaide | And 2 more authors.
Journal of Sexual Medicine | Year: 2014

Introduction: The progress and determinants of sexual dysfunction in middle-aged and elderly men remain unclear. Aim: To describe the incidence or remission and biopsychosocial predictors of erectile dysfunction (ED) and low sexual desire (SD). Main Outcome Measures: Erectile function (International Index of Erectile Function) and sexual desire (Sexual Desire Inventory 2) were assessed at follow-up. Sociodemographic, lifestyle, and health-related factors were examined in multivariate models of ED and low SD. Methods: Data were collected from 810 randomly selected men residing in northern and western Adelaide, Australia, and aged 35-80 years at baseline, who made clinic visits 5 years apart. Results: At baseline, 23.2% (n=123) of men had ED. ED incidence and remission were observed in 31.7% (n=179) and 29.0% (n=71) of eligible men, respectively. At baseline, 19.2% (n=165) had low solitary sexual desire, and 6.0% (n=50) had low dyadic sexual desire; incidence of low sexual desire occurred in 17.6% (n=83) (solitary) and 8.3% (n=51) (dyadic), while remission occurred in 15.4% (n=68) (solitary) and 22.6% (n=40) (dyadic) of men. In the final regression models, predictors of incident ED were higher age, lower income, higher abdominal fat mass, low alcohol intake, higher risk of obstructive sleep apnea (OSA) risk, voiding lower urinary tract symptoms (LUTS), depression, and diabetes. Predictors of ED remission were lower age, current employment, and absence of voiding LUTS, angina, diabetes, and dyslipidemia. Predictors of low dyadic SD incidence included higher age, never having been married, widowhood, being unemployed, being retired, insufficient physical activity, and low alcohol intake. Predictors of low dyadic SD remission were being married, not being widowed, higher income, lower abdominal fat mass, lower OSA risk, and higher plasma testosterone. Predictors of low solitary SD included never having been married, being unemployed, low alcohol intake, lower testosterone, storage LUTS, and hypertension. Predictors of low solitary SD remission were being married, being employed, higher income, higher physical activity, moderate alcohol intake, and depression. Conclusions: Sexual dysfunction in aging men is a dynamic disorder whose incidence and remission are predicted by a range of modifiable risk factors. © 2014 International Society for Sexual Medicine.

Anderson P.H.,University of South Australia | Lam N.N.,Chemical Pathology | Turner A.G.,University of South Australia | Davey R.A.,University of Melbourne | And 3 more authors.
Journal of Steroid Biochemistry and Molecular Biology | Year: 2013

A current controversial question related to vitamin D supplementation is what level of serum 25- hydroxyvitamin D3 (25(OH)D3) is required to reduce the incidence of osteoporotic fractures. The reasoning behind vitamin D supplementation has been mostly derived from the role of vitamin D to promote intestinal calcium absorption and reduce bone resorption. While minimum 25(OH)D3 levels of 20 nmol/L are required for sufficient intestinal calcium absorption to prevent osteomalacia, the mechanistic details of how higher 25(OH)D3 levels, well beyond that required for optimal calcium absorption, are able to prevent fractures and increase bone mineral density is unclear. Substantial evidence has arisen over the past decade that conversion of 25(OH)D3 to 1,25(OH)2D3 via the 1-alpha hydroxylase (CYP27B1) enzyme in osteoblasts, osteocytes, chondrocytes and osteoclasts regulates processes such as cell proliferation, maturation and mineralization as well as bone resorption, which are all dependent on the presence the of the vitamin D receptor (VDR). We and others have also shown that increased vitamin D activity in mature osteoblasts by increasing levels of VDR or CYP27B1 leads to improved bone mineral volume using two separate transgenic mouse models. While questions remain regarding activities of vitamin D in bone to influence the anabolic and catabolic processes, the biological importance of vitamin D activity within the bone is unquestioned. However, a clearer understanding of the varied mechanisms by which vitamin D directly and indirectly influences mineral bone status are required to support evidence-based recommendations for vitamin D supplementation to reduce the risk of fractures. Copyright © 2012 Published by Elsevier Ltd. All rights reserved.

Mitchell R.,University of Adelaide | Charlwood C.,Forensic Science SA | Thomas S.D.,Chemical Pathology | Bellis M.,Forensic Science SA | Langlois N.E.I.,University of Adelaide
Forensic Science, Medicine, and Pathology | Year: 2013

Biochemical analysis of the vitreous humor from the eye is an accepted accessory test for post-mortem investigation of cause of death. Modern biochemical analyzers allow testing of a range of analytes from a sample. However, it is not clear which analytes should be requested in order to prevent unnecessary testing (and expense). The means and standard deviation of the values obtained from analysis of the vitreous humor for sodium, potassium, chloride, osmolality, glucose, ketones (β-hydroxybutyrate), creatinine, urea, calcium, lactate, and ammonia were calculated from which the contribution of each analyte was reviewed in the context of post-mortem findings and final cause of death. For sodium 32 cases were regarded as high (more than one standard deviation above the mean), from which 9 contributed to post-mortem diagnosis [drowning (4), heat related death (2), diabetic hyperglycemia (2), and dehydration (1)], but 25 low values (greater than one standard deviation below the mean) made no contribution. For chloride 29 high values contributed to 4 cases-3 drowning and 1 heat-related, but these were all previously identified by a high sodium level. There were 29 high and 35 low potassium values, none of which contributed to determining the final cause of death. Of 22 high values of creatinine, 12 contributed to a diagnosis of renal failure. From 32 high values of urea, 18 contributed to 16 cases of renal failure (2 associated with diabetic hyperglycemia), 1 heat-related death, and one case with dehydration. Osmolarity contributed to 12 cases (5 heat-related, 4 diabetes, 2 renal failure, and 1 dehydration) from 36 high values. There was no contribution from 32 high values and 19 low values of calcium and there was no contribution from 4 high and 2 low values of ammonia. There were 11 high values of glucose, which contributed to the diagnosis of 6 cases of diabetic hyperglycemia and 21 high ketone levels contributed to 8 cases: 4 diabetic ketosis, 3 hypothermia, 3 ketosis of unknown cause, and 2 alcohol related deaths. A high lactate was identified in 25 cases, which contributed to 1 case with a diagnosis of metformin toxicity (1), but none of the 22 low lactate values contributed. The results of this audit have been used to reduce vitreous biochemistry test requests for sodium, osmolality, glucose, ketones, urea, and creatinine in most cases. Critical appraisal of each part of the post-mortem process should be undertaken to provide evidence to justify any investigative methods used in an autopsy. © 2013 Springer Science+Business Media New York.

Mitchell R.,University of Adelaide | Thomas S.D.,Chemical Pathology | Langlois N.E.I.,Forensic Science South Australia | Langlois N.E.I.,University of Adelaide
Pathology | Year: 2013

Aims: Biochemical analysis of glucose and ketones in the vitreous humour obtained at post-mortem examination is representative of the levels in the blood prior to death. Elevated levels can be indicative of conditions including diabetic ketoacidosis, which can be a cause for unexpected death. A rapid screening test for such conditions can be performed during the autopsy through urinalysis using test strips (urine 'dipstick' testing). The aim of this study was to assess the utility of urinalysis testing for post-mortem detection of derangements of glucose and ketone levels. Methods: The results of vitreous biochemical analysis and urinalysis were collated from 188 forensic autopsy cases. Results: A vitreous glucose result of above 10 mmol/L was regarded as high. When this was compared to urinalysis results it was found that any urinalysis result above negative had a sensitivity of 0.83 and a specificity of 0.93. A vitreous ketone level of above 5 mmol/L was regarded as significantly elevated; a urinalysis result above negative had a sensitivity of 1, but a specificity of 0.12. Conclusions: Urinalysis ('dipstick' testing) for glucose has a good sensitivity and specificity for high vitreous glucose levels, which are regarded as indicative of pathological hyperglycaemia during life. It was found that urine testing for ketones either has an excellent sensitivity with low specificity or a poor sensitivity with a good specificity; however, this finding has to be viewed in the context of uncertainty of the biochemical level of significant ketosis. © 2013 Royal College of Pathologists of Australasia.

Harris G.,MP Sports Physicians | Reid S.,Sports Medicine Practice | Sikaris K.,Chemical Pathology | McCrory P.,University of Melbourne | McCrory P.,Monash University
Clinical Journal of Sport Medicine | Year: 2012

Objective: To determine the incidence of and risk factors for exercise-associated hyponatremia (EAH) in cyclists completing a long-distance bike ride and to assess whether postexercise serum NT-proBNP concentration (brain natriuretic protein precursor) differed between riders with and without EAH. Design: Observational study. Setting: "Around the Bay in a Day" cycle event, October 2010. Participants: One hundred thirty-nine cyclists prospectively enrolled, with 90 completing 210 or 250 km. Main outcome measures: Body weight change and fluid intake during the event, and postevent serum sodium concentration ([Na]) and NT-proBNP concentration ([NT-proBNP]). Results: Four riders (4.5%) were hyponatremic ([Na] < 135 mmol/L). The lowest postride [Na] was 126 mmol/L. Hyponatremia was associated with a mean weight gain of 3.4 kg (3.9% of total body weight). Significant negative correlations were found between postride [Na] and change in weight (r =-0.34; P < 0.01) and fluid intake when expressed as total volume (r =-0.35; P < 0.01), mL/kg body weight (r = 0.33; P < 0.01), mL•kg•h (r =-0.27; P < 0.01), or mL/h (r =-0.29; P < 0.01). NT-proBNP concentrations levels in 3 of the 4 hyponatremic subjects were markedly elevated compared with eunatremic subjects matched for age, sex, distance ridden, training, and medical history. Conclusions: Exercise-associated hyponatremia was found to occur in 4.5% of the study group and was associated with weight gain during a prolonged bike ride. Postride [Na] varied inversely with weight change and with fluid intake. Three of 4 hyponatremic riders had significant elevations of [NT-proBNP]. These results support the hypothesis that overconsumption of hypotonic fluids in this setting is the most important cause of EAH. © 2012 Lippincott Willimas & Wilkins.

Briscoe S.E.,Chemical Pathology | McWhinney B.C.,Chemical Pathology | Lipman J.,Royal Brisbane and Womens Hospital | Lipman J.,University of Queensland | And 3 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2012

With the clinical imperative to further research in the area of optimising antibiotic dosing in the intensive care setting, a simple high performance liquid chromatography method was developed and validated for routinely determining the free (unbound) concentration of ten beta-lactam antibiotics in 200 μL of human plasma. Antibiotics determined include three cephalosporins (ceftriaxone, cephazolin and cephalotin); two carbapenems (meropenem and ertapenem); and five penicillins (ampicillin, piperacillin, benzylpenicillin, flucloxacillin and dicloxacillin). There was a single common sample preparation method involving ultracentrifugation and stabilisation. Chromatography was performed on a Waters XBridge C18 column with, depending on analytes, one of four acetonitrile-phosphate buffered mobile phases. Peaks of interest were detected via ultraviolet absorbance at 210, 260 and 304. nm. The method has been validated and used in a pathology laboratory for therapeutic drug monitoring in critically ill patients. The significant variability in the level of protein binding that is common with antibiotics traditionally considered to have high protein binding (e.g. ceftriaxone, cephazolin, ertapenem, flucloxacillin and dicloxacillin) suggests that this assay should be preferred for measuring the pharmacologically active concentration of beta-lactam antibiotics in a therapeutic drug monitoring programme. © 2012.

Wong G.,University of Queensland | Briscoe S.,Chemical Pathology | Adnan S.,University of Queensland | McWhinney B.,Chemical Pathology | And 5 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2013

The use of therapeutic drug monitoring (TDM) to optimize beta-lactam dosing in critically ill patients is growing in popularity, although there are limited data describing the potential impact of altered protein binding on achievement of target concentrations. The aim of this study was to compare the measured unbound concentration to the unbound concentration predicted from published protein binding values for seven beta-lactams using data from blood samples obtained from critically ill patients. From 161 eligible patients, we obtained 228 and 220 plasma samples at the midpoint of the dosing interval and trough, respectively, for ceftriaxone, cefazolin, meropenem, piperacillin, ampicillin, benzylpenicillin, and flucloxacillin. The total and unbound beta-lactam concentrations were measured using validated methods. Variabilities in both unbound and total concentrations were marked for all antibiotics, with significant differences being present between measured and predicted unbound concentrations for ceftriaxone and for flucloxacillin at the mid-dosing interval (P<0.05). The predictive performance for calculating unbound concentrations using published protein binding values was poor, with bias for overprediction of unbound concentrations for ceftriaxone (83.3%), flucloxacillin (56.8%), and benzylpenicillin (25%) and underprediction for meropenem (12.1%). Linear correlations between the measured total and unbound concentrations were observed for all beta-lactams (R2= 0.81 to 1.00; P<0.05) except ceftriaxone and flucloxacillin. The percent protein binding of flucloxacillin and the plasma albumin concentration were also found to be linearly correlated (R2=0.776; P<0.01). In conclusion, significant differences between measured and predicted unbound drug concentrations were found only for the highly protein-bound beta-lactams ceftriaxone and flucloxacillin. However, direct measurement of unbound drug in research and clinical practice is suggested for selected beta-lactams. Copyright © 2013, American Society for Microbiology. All Rights Reserved.

Anderson P.H.,Chemical Pathology | Iida S.,Hokkaido University | Tyson J.H.T.,Chemical Pathology | Turner A.G.,Chemical Pathology | And 2 more authors.
Journal of Steroid Biochemistry and Molecular Biology | Year: 2010

Although the regulation of renal 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) is reasonably well understood, the same cannot be said about the regulation of bone CYP27B1 expression. We have compared the regulation of kidney and bone CYP27B1 expression with modulation of dietary vitamin D and calcium levels. Vitamin D-deplete and vitamin D-replete female Sprague-Dawley rats were fed either 1% Ca (HC) or 0.1% Ca (LC) diets from 6 months of age. At 9 months of age, animals were killed for mRNA analyses from kidney and bone by real-time RT-PCR. Additionally, primary bone cells were cultured from pCYP27B1-Luc reporter mice in pro-osteogenic media over 15 days and analysed for mRNA for CYP27B1 and other osteogenic markers. In vivo expression of bone CYP27B1 mRNA was independent of changes to kidney CYP27B1 levels with both serum 1,25D and PTH as negative determinants of bone CYP27B1 mRNA levels. Bone cells in pro-mineralising conditions significantly increased CYP27B1 promoter activity over 15 days (P<0.001) which preceded marked increases in alkaline phosphatase, osteocalcin and vitamin D receptor mRNA expression and mineral deposition. These findings confirm that the regulation of bone CYP27B1 is unique from that in the kidney, and may play an important role in bone formation. © 2010.

McWhinney B.C.,Chemical Pathology | Wallis S.C.,University of Queensland | Hillister T.,Chemical Pathology | Roberts J.A.,University of Queensland | And 2 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2010

A simple and economical high performance liquid chromatography method was developed and validated for routine analysis of 12 Penicillin, Cephalosporin and Carbapenem antibiotics in 200. μL of human plasma. Antibiotics determined were Ceftazidime, Meropenem, Ceftriaxone, Ampicillin, Cefazolin, Ertapenem, Cephalothin, Benzylpenicillin, Flucloxacillin, Dicloxacillin, Piperacillin and Ticarcillin. There was a common sample preparation approach involving precipitation of proteins with acetonitrile and removal of lipid-soluble components by a chloroform wash. Separations were performed on a Waters X-bridge C18 column with, depending on analytes, one of three acetonitrile-phosphate buffer mobile phases. Detection was by UV at 210, 260 and 304. nm. Validation has demonstrated the method to be linear, accurate and precise. The method has been used in a pathology laboratory for therapeutic drug monitoring (TDM) of beta-lactams in critically ill patients. © 2010.

Hassan A.,Chemical Pathology | Mehaney D.,Cairo University
Egyptian Journal of Neurology, Psychiatry and Neurosurgery | Year: 2015

Background: Multiple sclerosis (MS) is a primary inflammatory demyelinating disease that could be associated with a secondary progressive neurodegenerative component. Objective: To investigate the serum levels of lactate and uric acid (UA) in MS patients and to explore their potential role as biological markers for monitoring the disease activity and progression. Methods: This case-control study was conducted on 89 Egyptian subjects (55 multiple sclerosis patients=Group I) and 34 normal healthy individuals (Control group = Group II). Group I patients were subjected to thorough history taking, detailed neurological examination and clinical assessment of the severity of the disease using Expanded Disability Status Scale (EDSS). Serum level of lactate and uric acid were measured in both groups. Results: In comparison to the control group, subjects with multiple sclerosis had statistically significant higher serum level of lactate (P=0.005), along with lower serum levels of UA (P=0.001), however, there was no statistically significant correlation between their levels and duration of illness, EDSS scores or number of attacks. Conclusion: MS patients have significantly higher serum lactate level. This can support the hypothesis that mitochondrial dysfunction has an important role in the underlying pathogenic mechanism of the disease. MS patients have also significantly lower uric acid level than normal control; reflecting its important role as an antioxidant in the prevention of disease activity. However, their potential value as markers for monitoring disease activity and progression is questionable. © 2015, Egypt J Neurol Psychiat Neurosurg. All rights reserved.

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