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PubMed | Murdoch Childrens Research Institute, Labtests, Institute of Environmental Science and Research, University of Auckland and University of Melbourne
Type: Journal Article | Journal: BMC infectious diseases | Year: 2016

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are responsible for a significant disease burden amongst Mori and Pacific populations in New Zealand (NZ). However, contemporary data are lacking regarding circulating group A Streptococcal (GAS) strains in NZ. Such information is important in guiding vaccine development.GAS isolates from April to June 2015 were recovered from skin and pharyngeal samples from children living in areas of high social deprivation in Auckland, NZ, a significant proportion of which are Mori or Pacific. These children are among the highest risk group for developing ARF. Isolates were compared to concurrently collected pharyngeal isolates from Dunedin, NZ, where both the proportion of Mori and Pacific children and risk of developing ARF is low. Emm typing, emm cluster typing and theoretical coverage of the 30-valent vaccine candidate were undertaken as previously described.A high diversity of emm types and a high proportion of emm-pattern D and cluster D4 isolates were detected amongst both skin and pharyngeal isolates in children at high risk of ARF. Pharyngeal isolates from children at low risk of ARF within the same country were significantly less diverse, less likely to be emm pattern D, and more likely to be theoretically covered by the 30-valent M protein vaccine.The high proportion of emm pattern D GAS strains amongst skin and pharyngeal isolates from children at high risk of ARF raises further questions about the role of skin infection in ARF pathogenesis. Emm types and emm clusters differed considerably between ARF endemic and non-endemic settings, even within the same country. This difference should be taken into account for vaccine development.

Park T.I.-H.,University of Auckland | Monzo H.,University of Auckland | Mee E.W.,Auckland City Hospital | Bergin P.S.,Auckland City Hospital | And 5 more authors.
PLoS ONE | Year: 2012

The ability to culture neural progenitor cells from the adult human brain has provided an exciting opportunity to develop and test potential therapies on adult human brain cells. To achieve a reliable and reproducible adult human neural progenitor cell (AhNPC) culture system for this purpose, this study fully characterized the cellular composition of the AhNPC cultures, as well as the possible changes to this in vitro system over prolonged culture periods. We isolated cells from the neurogenic subventricular zone/hippocampus (SVZ/HP) of the adult human brain and found a heterogeneous culture population comprised of several types of post-mitotic brain cells (neurons, astrocytes, and microglia), and more importantly, two distinct mitotic cell populations; the AhNPCs, and the fibroblast-like cells (FbCs). These two populations can easily be mistaken for a single population of AhNPCs, as they both proliferate under AhNPC culture conditions, form spheres and express neural progenitor cell and early neuronal markers, all of which are characteristics of AhNPCs in vitro. However, despite these similarities under proliferating conditions, under neuronal differentiation conditions, only the AhNPCs differentiated into functional neurons and glia. Furthermore, AhNPCs showed limited proliferative capacity that resulted in their depletion from culture by 5-6 passages, while the FbCs, which appear to be from a neurovascular origin, displayed a greater proliferative capacity and dominated the long-term cultures. This gradual change in cellular composition resulted in a progressive decline in neurogenic potential without the apparent loss of self-renewal in our cultures. These results demonstrate that while AhNPCs and FbCs behave similarly under proliferative conditions, they are two different cell populations. This information is vital for the interpretation and reproducibility of AhNPC experiments and suggests an ideal time frame for conducting AhNPC-based experiments. © 2012 Park et al.

Upton A.,Labtests | Bromhead C.,Aotea Pathology Ltd. | Whiley D.M.,University of Queensland
Journal of Clinical Microbiology | Year: 2013

The Roche cobas 4800 CT/NG assay is a commonly used commercial system for screening for Neisseria gonorrhoeae infection, and previous studies have shown the method to be highly sensitive and specific for urogenital samples. We present the first confirmed clinical N. gonorrhoeae false-positive result using the cobas 4800 NG assay, obtained from testing a pharyngeal swab sample and caused by cross-reaction with a commensal Neisseria strain. Copyright © 2013, American Society for Microbiology.

Wong W.K.,University of Auckland | Upton A.,Labtests | Thomas M.G.,University of Auckland
Scandinavian Journal of Infectious Diseases | Year: 2013

Background: Chronic toxoplasmosis has been shown to be strongly associated with a range of neuropsychiatric effects including schizophrenia and suicide. However there have not been any prospective, community-based studies of the neuropsychiatric effects of acute toxoplasmosis in adult immunocompetent patients. Methods: Adult patients with a positive serum IgM anti-Toxoplasma gondii test result, in the context of an acute illness with lymphadenopathy, were invited to complete a questionnaire seeking information relating to the nature, severity, and duration of symptoms in the months following the diagnosis of acute toxoplasmosis. Results: Laboratory testing identified a total of 187 adults who had a positive serum IgM anti-T. gondii test result between 1 January and 30 November 2011. Consent to contact 108/187 (58%) patients was provided by their family doctor; 37 (34%) of these 108 patients completed and returned the questionnaire. Questionnaires from the 31/108 (29%) patients who reported swollen lymph nodes during their illness were included in the study. Fatigue (90%), headache (74%), difficulty concentrating (52%), and muscle aches (52%) were the most commonly reported symptoms. These symptoms commonly persisted for at least 4 weeks. Twenty-seven of 31 (87%) subjects reported a moderate or severe reduction in their overall physical and mental health during the first 2 months of illness. Conclusions: Acute toxoplasmosis in immunocompetent adults commonly causes moderately severe neuropsychiatric symptoms that might result from replication of the organism in the central nervous system with consequent effects on brain function. Patients should be advised that such symptoms are common and reassured that they usually resolve completely within a few months. © 2013 Informa Healthcare.

Barron J.,Labtests
Journal of Clinical Pathology | Year: 2010

The aim of this article is to provide knowledge of the origin of catecholamines and metabolites so that there can be an informed approach to the methods for biochemical screening for a possible phaeochromocytoma; The article includes a review of catecholamine and metadrenaline metabolism, with methods used in biochemical screening. In the adrenal medulla and a phaeochromocytoma, catecholamines continuously leak from chromaffin granules into the cytoplasm and are converted to metadrenalines. For a phaeochromocytoma to become biochemically detectable, metnoradrenaline secretion needs to rise fourfold, whereas noradrenaline secretion needs to rise 15-fold. The prevalence of a sporadic phaeochromocytoma is low; therefore false-positive results exceed truepositive results. Assay sensitivity is high because it is important not to miss a possible phaeochromocytoma. The use of urine or plasma fractionated metadrenalines as the first-line test has been recommended due to improved sensitivity. A negative result excludes a phaeochromocytoma. Only after a sporadic phaeochromocytoma has been diagnosed biochemically is it cost effective to request imaging. Sensitivities and specificities of the assays differ according to pre-test probabilities of the presence of a phaeochromocytoma, with hereditary and incidentalomas having a higher pre-test probability than sporadic phaeochromocytoma. In conclusion, in screening for a possible phaeochromocytoma, biochemical investigations should be completed first to exclude or establish the diagnosis. The preferred biochemical screening test is fractionated metadrenalines, including methoxytyramine so as not to miss dopamine-secreting tumours.

Evans G.E.,University of Otago | Phillipson G.T.M.,Repromed | Sin I.L.,Repromed | Frampton C.M.A.,University of Otago | And 3 more authors.
Human Reproduction | Year: 2012

BACKGROUND To use contemporary biochemical markers to characterize mRNA/gene expression in the potentially fertile secretory endometrium to confirm its identification based on histological characteristics in order to develop a clinically applicable test. METHODS Nine, fertile, cycling Caucasian women were sampled from one IVF clinic. Endometrial samples were collected from them in two to four menstrual cycles at 2 and 7 days post first significant rise in blood LH. Separate endometrial glands and stroma populations were obtained by laser microdissection. Linear polymerase chain reaction amplified mRNAs which were hybridized to both Affymetrix U133 Plus2 and Agilent 4×44K microarrays followed by gene set analysis. Four histopathologists reviewed the sample set using the same histological criteria to date and characterize the non-receptive and potentially receptive samples. RESULTS mRNA expression of microdissected glands and stroma provided molecular signatures that characterized the two specific phases of the cycle with distinct clustering patterns. Cell proliferation and five other associated biological pathways were significantly down-regulated when the endometrium is considered potentially receptive accompanied by an increase in secreted glycoproteins mRNAs in the potentially receptive glands. Reported histological findings identified the presence of one histological feature characteristic of each phase: glandular mitoses indicated a non-receptive endometrium, whereas a potentially receptive endometrium was distinguished by supranuclear vacuolation. CONCLUSIONS This study defined a transcriptome characteristic of active cell proliferation in the non-receptive samples with a marked overall down-regulation of this pathway in potentially receptive samplessuggesting a transitional state associated with receptivity but not implantation. However, microarrays involve expensive, specialized testing and require significant post-data analysis. Sampling according to endocrinological and molecular prediction improved the consistency of histological assessment and allowed reliable histological markers of glandular mitosis in the non-receptive phase and supranuclear vacuolation of the potentially receptive endometrium to be identified. Thus, histology can provide an affordable, clinically applicable test in the context of reproduction. © The Author 2012.

Upton A.,Labtests | Lowe C.,Labtests | Stewart J.,University of Auckland | Taylor S.,Middlemore Hospital | Lennon D.,University of Auckland
New Zealand Medical Journal | Year: 2014

Aims To examine the analytical sensitivity of four rapid antigen tests (RADT) for detection of group A streptococcus (GAS). Methods The sensitivities of four RADT kits to detect clinical and reference strains of GAS at different dilutions were compared. Test results were read by two people, and differences in interpretation were settled by a third reader. Results A total of 697 tests were performed. For all kits, detection increased with increasing colony counts of GAS. One kit [ulti med Products, Deutschland, GmbH (UM)] was found to have the highest sensitivity, although there was no significant difference between it and one other kit (Testpack Plus). All kits were only faintly positive or negative at low colony counts. Conclusions The sensitivity of RADT for detecting GAS is related to inoculum size and the faint appearance of a positive test at low colony counts contributes to interobserver variability. Sore throats with low colony counts have been shown to be clinically relevant. ©NZMA.

Mikkelsen D.,Labtests
New Zealand Journal of Medical Laboratory Science | Year: 2013

Errors will occur in medical laboratories at a rate that is no different to any complex industry. For the most part these errors have little or no consequence because the systems that are in place act as or provide barriers to prevent common and simple human errors from causing consequences for users of our services. From time to time a sequence of errors or departures from Standard Operating Procedures (SOPs) will occur that defeat systems that are in place and a consequence of these errors will be the outcome. Consequences can range from undetectable, for example a normal result from patient x is replaced by a normal result from patient y, through to inappropriate therapy dispensed to a patient based on an erroneous investigation resulting in serious morbidity or worse. It is important therefore that errors are detected early and managed appropriately. The primary reason is to ensure that corrective action can be undertaken to eliminate or moderate the impact of the error. The important secondary reason is so that we may learn from the error and work to avoid the error in the future. The occurrence of errors is therefore an important trigger for quality improvement activity. Laboratory systems are inanimate and require people to make them function. There are three behaviours expected from humans working within any system: 1. Human Error resulting from the inherent weaknesses of human performance 2. At-risk behaviour 3. Reckless behaviour. This triad of behaviours are to be expected within any workforce and our response as leaders needs to be appropriate in each behaviour type in order to assign the correct level of accountability. Accountability for situations that develop purely from human error should entirely attach to the system and not the individual. Medium level accountability should be attached to those who undertake at-risk behaviour and should initially be centred on coaching. Individual accountability should escalate in repeat occurrences of at risk behaviour. Reckless behaviour where risks are known and deliberately ignored should have maximum individual accountability attached. Achieving a better organisational understanding of human factors involved in error forms and a system of fair accountability will stimulate individuals to report errors that occur and openly contribute to a process improvement culture that seeks to learn from error and make systems more resilient and failsafe. © 2013 The author.

Upton A.,Labtests | Wilson J.,Labtests | Bissessor L.,Labtests
Sexual Health | Year: 2013

We introduced polymerase chain reaction (PCR) testing for Neisseria gonorrhoeae (NG) on the Cobas 4800 CT/NG assay for all samples received with a Chlamdyia trachomatis request in March 2012. From 1 March 2012 to 30 June 2012, all PCR-positive/culture-negative specimens had additional testing at another assay. A total of 40053 tests were performed. The estimated specificity and positive predictive value were 99.9% and 97.1%, respectively; thus routine additional testing is not required. © CSIRO 2013.

Aims: Streptococcus pyogenes or group A streptococcus (GAS) is a common cause of vulvo-vaginitis in pre-pubertal females but is uncommonly isolated from the vaginal swabs of adult females. We aimed to describe the clinical and laboratory findings of adult females with GAS isolated from vaginal swabs in a community and hospital laboratory. Methods: Over a 19 week period the two laboratories identified females ≥15 years of age with GAS isolated from vaginal swabs. At least 2 weeks after reporting, the referring doctor or midwife was telephoned by the authors for clinical information or the clinical notes were reviewed. Laboratory data were also collected. Results: One hundred adult females with GAS isolated from vaginal swabs were identified from approximately 4500-5000 community laboratory and 20 from approximately 2000 hospital laboratory swabs. Community patients were more likely to have presented with vaginal symptoms such as discharge, while hospital patients were more likely to have ascending infection related to pregnancy/recent delivery. Of the community patients, 15% were asymptomatic compared with 5% of the hospital patients. Review of Gram stain and culture quantification was not found to be particularly useful for discriminating between clinical infection and asymptomatic colonisation. Conclusions: Isolation of GAS from the vaginal swabs of adult females is uncommon. In the community setting it may represent infection with vulvo-vaginitis or asymptomatic colonisation. In the hospital setting, its isolation is frequently associated with pregnancy-related infectious complications. © 2013 Royal College of Pathologists of Australasia.

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