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Sydney, Australia

Beyer C.E.,Monash IVF | Kayler B.,Healthscope Pathology | Osborne E.,Monash IVF | McLachlan R.,Monash IVF | And 3 more authors.
Fertility and Sterility | Year: 2012

Objective: To compare the clinical utility of a supersensitive fluorescent semen analysis (SSSA) procedure published by Cooper et al. (2006) with a conventional World Health Organization (WHO)-based semen analysis technique in males with severe oligozoospermia or azoospermia who are undergoing fertility assessment. Design: Prospective single-center study. Setting: IVF clinic. Patient(s): Patients attending an infertility clinic for semen analysis. Intervention(s): None. Main Outcome Measure(s): Presence of spermatozoa in the ejaculate. Result(s): Semen samples from 100 men were analyzed using conventional WHO 4th Edition semen analysis and determined to be either severely oligozoospermic or azoospermic (reported lower limit of detection of 0.1 million sperm/mL). An aliquot of the same unprocessed sample was also analyzed using the SSSA protocol (reported lower limit of detection of approximately 8000 sperm/mL). The SSSA method confirmed the results of conventional semen analysis in 77% of cases. In 22% of cases, sperm were identified only using SSSA. Overall, SSSA was capable of identifying the presence of sperm in significantly more samples than conventional semen analysis. Conclusion(s): The reliable differentiation of extreme oligospermia from azoospermia has profound implications in fertility management. This paper provides the first data comparing sperm detection rates using SSSA or conventional WHO-based approaches in extreme oligozoospermic and azoospermic men in an IVF setting. Results indicate that approximately one in four men classified as azoospermic by conventional semen analysis may actually have sperm present. The improved sensitivity of the SSSA technique may be of significant benefit to patients, particularly in fertility and assisted reproductive technique decision making. © 2012 American Society for Reproductive Medicine, Published by Elsevier Inc.

Hanna W.M.,University of Toronto | Ruschoff J.,Institute of Pathology Nordhessen | Bilous M.,Healthscope Pathology | Coudry R.A.,State of Sao Paulo Cancer Institute ICESP | And 5 more authors.
Modern Pathology | Year: 2014

Trastuzumab-containing therapy is a standard of care for patients with HER2+ breast cancer. HER2 status is routinely assigned using in situ hybridization to assess HER2 gene amplification, but interpretation of in situ hybridization results may be challenging in tumors with chromosome 17 polysomy or intratumoral genetic heterogeneity. Apparent chromosome 17 polysomy, defined by increased chromosome enumeration probe 17 (CEP17) signal number, is a common genetic aberration in breast cancer and represents an alternative mechanism for increasing HER2 copy number. Some studies have linked elevated CEP17 count ('polysomy') with adverse clinicopathologic features and HER2 overexpression, although there are numerous discrepancies in the literature. There is evidence that elevated CEP17 ('polysomy') count might account for trastuzumab response in tumors with normal HER2:CEP17 ratios. Nonetheless, recent studies establish that apparent 'polysomy' (CEP17 increase) is usually related to focal pericentromeric gains rather than true polysomy. Assigning HER2 status may also be complex where multiple cell subclones with distinct HER2 amplification characteristics coexist within the same tumor. Such genetic heterogeneity affects up to 40% of breast cancers when assessed according to a College of American Pathologists guideline, although other definitions have been proposed. Recent data have associated heterogeneity with unfavorable clinicopathologic variables and poor prognosis. Genetically heterogeneous tumors harboring HER2-amplified subclones have the potential to benefit from trastuzumab, but this has yet to be evaluated in clinical studies. In this review, we discuss the implications of apparent polysomy 17 and genetic heterogeneity for assigning HER2 status in clinical practice. Among our recommendations, we support the use of mean HER2 copy number rather than HER2:CEP17 ratio to define HER2 positivity in cases where coamplification of the centromere might mask HER2 amplification. We also highlight a need to harmonize in situ hybridization scoring methodology to support accurate HER2 status determination, particularly where there is evidence of heterogeneity. © 2014 USCAP, Inc.

Glasson J.,LBT Innovations Ltd | Hill R.,University of Adelaide | Summerford M.,LBT Innovations Ltd | Giglio S.,Healthscope Pathology
Journal of Clinical Microbiology | Year: 2016

While advancements have been made in some areas of pathology with diagnostic materials being screened using image analysis technologies, the reporting of cultures from agar plates remains a manual process. We compared the results for 2,163 urine cultures read by a reference panel of microbiologists, by the routine laboratory process, and by an automated plate reading system, APAS (LBT Innovations Ltd., South Australia). APAS detected colonies with a sensitivity of 99.1% and a specificity of 99.3% on blood agar, while on MacConkey agar, the colony detection sensitivity was 99.4% with a specificity of 99.3%. The device's ability to enumerate growth had an accuracy of 89.2%, and the morphological identification of colonies showed a high level of performance for the colony types typical of Escherichia coli and other enteric bacilli. On blood agar, lactose-fermenting colonies were morphologically identified with a sensitivity of 98.9%, while on MacConkey agar they were identified with a sensitivity of 99.2%. In this first clinical evaluation, APAS demonstrated high performance in the detection, enumeration, and colony classification of isolates compared with that for conventional plate-reading methods. The device found all cases reported by the laboratory and detected the most commonly encountered organisms found in urinary tract infections. Copyright © 2016 Mokhtari et al.

Singh A.B.,Deakin University | Singh A.B.,University of Melbourne | Bousman C.A.,University of Melbourne | Bousman C.A.,Florey Institute for Neuroscience and Mental Health | And 7 more authors.
International Clinical Psychopharmacology | Year: 2013

Predicting differential antidepressant efficacy remains an elusive goal in major depressive disorder (MDD). The aims of this study were three-fold. Firstly, to examine if psychomotor retardation symptoms (item 8 on the 17-item Hamilton Depression Rating Scale) improve preferentially to venlafaxine (VEN) over escitalopram (ESC) treatment. Secondly, whether the 18 item CORE psychomotor signs scale predicted antidepressant remission. Finally, to investigate the role of two norepinephrine transporter gene (NET) polymorphisms (rs2242446 and rs5569) on antidepressant efficacy. Adults with Diagnostic and Statistical Manual of Mental Disorders, 4th ed. MDD (n=113) were treated with ESC or VEN prospectively for 8 weeks and rated serially with the Hamilton Depression Rating Scale. In a subsample (n=51) of patients from one of the three recruitment sites, the CORE psychomotor signs scale was also administered at baseline. Participants treated with VEN had significantly greater reduction in psychomotor retardation symptoms than those treated with ESC. The CORE scale did not predict antidepressant response or remission. Neither NET polymorphism moderated antidepressant efficacy. Findings suggest possible preferential utility of a selective serotonin and noradrenaline reuptake inhibitor in cases of MDD presenting with greater psychomotor retardation. The moderate to small sample size makes a type II error risk possible, and the negative findings need to be interpreted with caution. The positive finding of preferential efficacy of VEN for psychomotor retardation symptoms has potential translational utility. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Pathmanathan N.,Institute of Clinical Pathology and Medical Research | Pathmanathan N.,Westmead Breast Cancer Institute | Pathmanathan N.,University of Sydney | Michael Bilous A.,Healthscope Pathology
Pathology | Year: 2012

Testing for HER2 positivity in breast cancer carries implications for prognosis and therapeutic response in patients. In recent times there have been numerous developments and refinements in the available technologies for HER2 testing. In addition to this, guidelines have been developed and modified in an attempt to improve reliability and accuracy of testing. Immunohistochemistry and FISH testing have been the most widely used methodology, and the technique which has the largest knowledge base. Some of the inherent disadvantages have prompted the development of newer brightfield techniques which overcome some of these issues. There is gathering experience with these emerging technologies. Despite efforts to optimise and standardise procedures there remains a small percentage of cases that continue to be unresolved, whether this be due to issues of polysomy of chromosome 17, other complex genetic changes or analytical/ interpretative issues. An ideal method for the resolution of these equivocal results should be considered in a specialised testing/referral centre, and this may include karyotyping studies of chromosome 17 or multiple probes for chromosome 17 using fluorescence in situ hybridisation or multiplex ligation-dependent probe amplification. It is timely to review of some of the newer techniques available for routine testing and approaches for cases which prove difficult to resolve using conventional testing methodology. © 2012 Royal College of Pathologists of Australasia.

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