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Solares C.A.,Georgia Regents University | Boyle G.M.,Queensland Institute of Medical Research | Brown I.,Sullivan and Nicolaides Pathology | Parsons P.G.,Queensland Institute of Medical Research | Panizza B.,Princess Alexandra Hospital Skull Base Unit
Otolaryngology - Head and Neck Surgery | Year: 2010

Objective: Perineural invasion (PNI) in cutaneous squamous cell carcinoma of the head and neck (CSCCHN) carries poor prognosis. Tumor markers associated with neurotropism in CSCCHN have not been identified. Our objective was to study the expression of αB-crystallin in CSCCHN with neurotropism. Study Design: Cross-sectional review of pathologic specimens. Setting: Tertiary care center. Subjects and Methods: Tissue from patients with CSCCHN with clinical PNI who underwent surgery between 1998 and 2005 was immunostained for αB-crystallin. In addition, non-PNI CSCCHN and normal nerve sections were also stained. Staining intensity was calculated by the histologic, or H, score (product of the intensity and proportion of tumor cells stained). The H-score ranged from 0.0 to 3.0, with 0 indicating negative staining in all cells and 3.0 indicating strong staining in 100 percent of cells. Results: Tissue was available in 15 clinical PNI CSCCHN patients. The analysis was also carried out in 14 non-PNI patients matched by stage and four normal greater auricular nerve (GAN) sections. The mean H-score was 0.56 for CSCCHN with PNI, 1.06 for non-PNI CSCCHN, and 3.0 for normal nerves. The difference in H-score between PNI and non-PNI CSCCHN was statistically significant (P = 0.04). Conclusion: CSCCHN with clinical PNI has decreased staining for αB-crystallin. This finding further demonstrates the differences between clinical PNI and non-PNI CSCCHN tumors. Additional studies are required to identify cell surface markers expressed by CSCCHN that confer neurotropism capabilities. © 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation.

Piliouras P.,Royal Brisbane and Womens Hospital | Piliouras P.,University of Queensland | Allison S.,University of Queensland | Rosendahl C.,University of Queensland | And 2 more authors.
Australasian Journal of Dermatology | Year: 2011

Background/Objectives: Tinea nigra is a relatively uncommon dematiaceous fungal infection of the palms and soles, which clinically may mimic a melanocytic lesion. We sought to ascertain how frequently misdiagnosis of this infection occurred and whether the use of dermoscopy helped in its diagnosis. Methods: Fifty consecutive cases of tinea nigra diagnosed at a dermatopathology laboratory were examined with regard to the clinical diagnosis, use of dermoscopy and the mode of management. Results: Of the 50 cases, 21 (42.0%) were treated by shave or surgical excision. The clinical diagnosis of tinea nigra was made in five cases (10.0%) and suggested along with other diagnoses in a further two cases (4.0%). The dermatologists (n = 9) gave the correct diagnosis in four patients (44.4%), the general practitioners (n = 38) gave the correct diagnosis in one patient (2.6%) and the three surgeons involved did not give the correct diagnosis. When dermoscopy was used, in seven of 13 (53.8%) cases tinea nigra was suggested as a probable diagnosis but when dermoscopy was not used (n = 37) tinea nigra was not clinically diagnosed (P < 0.001). Conclusions: The diagnosis of tinea nigra is significantly improved by dermoscopy, the disease should be considered as a cause of palmar or plantar pigmentation. © 2011 The Authors; Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.

Gaskin B.J.,Royal Brisbane and Womens Hospital | Fernando B.S.,Royal Brisbane and Womens Hospital | Sullivan C.A.,Royal Brisbane and Womens Hospital | Whitehead K.,Sullivan and Nicolaides Pathology | And 2 more authors.
British Journal of Ophthalmology | Year: 2011

Objective: The aims of this study were to determine the significance of expression of DNA mismatch repair proteins in detecting systemic malignancies in a series of patients with periocular sebaceous cell carcinoma and to determine the clinical characteristics and frequency of Muir-Torre syndrome in this cohort. Design: The study was a retrospective non-comparative interventional case series. Participants: 31 patients with histologically proven sebaceous cell carcinoma of the eyelid participated in the study. Methods: The authors made use of retrospective chart review and immunohistochemical staining of specimens. Main outcome measures: The main outcome measures are as follows: location, tumour size, sites of origin, growth patterns, management, histopathological and immunohistochemical findings, metastasis, other visceral malignancies and mortality. Results: The median age of presentation of the 31 patients in this study was 71 years (range 35-92 years). There was a near-equal gender distribution (M:F-14:17). The average follow-up was 72 months. Seventeen patients had tumours arising from the upper lid, 13 from the lower lid and 1 from the caruncle. Nine patients had clinical Muir-Torre syndrome. Four patients were positive for microsatellite instability complexes and four were negative. Histologically, 14 patients had a high-grade tumour, 13 were intermediate grade and 4 were low grade. Based on the in situ pattern, six patients had a bowenoid pattern, five had both bowenoid and pagetoid patterns and two had a pagetoid pattern. Eighteen patients had no in situ disease detected. Twenty-one patients were alive without disease, and two were alive with disease. Six patients had died, five from other causes and one from the disease. Conclusions: Visceral malignancies are common in patients with periocular sebaceous cell carcinoma. Approximately one in eight demonstrated a heritable risk for further visceral malignancy through failure to express DNA mismatch repair proteins. Diagnosis of periocular sebaceous cell carcinoma should prompt physicians to search for other associated malignancies. Immunohistochemical characterisation of these sebaceous lesions is useful in identifying increased risk in affected patients and family members.

Ahmed A.H.,University of Queensland | Calvird M.,Logan Beaudesert Health Service District | Gordon R.D.,University of Queensland | Taylor P.J.,University of Queensland | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Background: Plasma aldosterone to renin ratio (ARR) is the most popular screening test for primary aldosteronism (PAL). Certain medications are known to cause false-negative or -positive ARRs by affecting renin and aldosterone levels. There are no previously published data on the effects of antidepressants on ARR. Methods: Normotensive, depressed male patients (n.26) underwent measurement (seated, midmorning) of plasma aldosterone, direct renin concentration (DRC), renin activity (PRA), electrolytes and creatinine and urinary aldosterone, cortisol, electrolytes, and creatinine at baseline and after 2 and 6 wk treatment with sertraline (n . 14) or escitalopram (n . 12). Results: For both antidepressants, treatment was associated with rises in aldosterone [sertraline: baseline, mean ± SD, 243 ± 34; 2 wk, 256 ± 33; 6 wk, 267 ± 34 pmol/liter (P < 0.01 by ANOVA); escitalopram, 261±36, 269±38, 282±40 pmol/liter (P<0.05)], DRC [19.5±2.2, 33.5±2.0, 39.0± 2.4 mU/liter (P<0.001); 24.5±2.4, 34.0±2.7, 42.8±2.4 mU/liter (P<0.001)], and PRA [2.24±0.21, 2.58 ± 0.26, 4.68 ± 0.42 ng/ml . h (P < 0.001); 4.31 ± 0.22, 5.57 ± 0.36, 6.42 ± 0.53 ng/ml . h (P < 0.001)]. ARR fell significantly whether calculated using DRC [sertraline, 13.7 ± 2.2, 7.5 ± 0.7, 6.8 ± 0.7 (P < 0.001); escitalopram, 11.5 ± 1.9, 8.0 ± 1.1, 6.6 ± 1.0 (P < 0.001)], or PRA [116.6 ± 15.8, 108.4 ± 15.6, 60.4 ± 6.2 (P < 0.001); 61.2 ± 8.1, 50.0 ± 7.7, 45.6 ± 6.0 (P < 0.01)].Conclusion: Selective serotonin reuptake inhibitor antidepressants can significantly reduce ARR and therefore potentially increase the risk of false-negative resultswhenscreening for PAL. Further studies in hypertensive patients, including patients with confirmed PAL, are required. Copyright © 2011 by The Endocrine Society.

PubMed | Sullivan and Nicolaides Pathology, Örebro University, University of Queensland and Queensland University of Technology
Type: Journal Article | Journal: Environmental pollution (Barking, Essex : 1987) | Year: 2016

Per- and polyfluoroalkyl substances (PFASs) are a family of compounds that includes numerous compound classes. To date, only a subset of these PFASs have been studied thoroughly in the general population. In this study, pooled serum samples from Australia collected in 2002-2013 were analyzed for PFASs according to gender and age (age categories of 0-4 years, 5-15 years, 16-30 years, 31-45 years, 46-60 years, and >60 years), in total 54 pooled samples and 4920 individuals. Compound classes included were perfluorocarboxylic acids (PFCAs), perfluorosulfonic acids (PFSAs), and two groups of PFCA precursor compounds; polyfluoroalkyl phosphate diesters (diPAPs), and fluorotelomer sulfonic acids (FTSAs). Several PFASs that were not reported in previous studies of Australian serum samples were found in this sample set including; diPAPs, FTSAs, perfluoropentane sulfonic acid (PFPeS), perfluoroheptane sulfonic acid (PFHpS), perfluoroheptane carboxylic acid (PFHpA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), and perfluorotridecanoic acid (PFTrDA). Various temporal trends were observed with a significant reduction (p<0.05) between 2002 and 2013 for 8:2 FTSA, perflurohexane sulfonic acid (PFHxS), PFHpS, PFOS, and perflurooctanoic acid (PFOA). Levels of longer-chained PFDA and PFUnDA started to decrease more recently, between 2006 and 2013, while PFDoDA increased during the same time period. Higher levels in younger age groups (0-4 and 5-15 years) compared to adults (>15 years) were found for 8:2 FTSA and PFHpA, while levels of PFHpS, PFOS, PFUnDA, PFDoDA and PFTrDA were higher in adult age groups compared to younger age groups. Gender-specific patterns were seen for PFOA, PFHxS, PFHpS and PFOS, where levels were lower in women. Changes in manufacturing processes were reflected in the temporal time trends, and differences in bioaccumulation potential between homologues could be associated with age trends. Our results emphasize the importance of including emerging classes of PFASs in biomonitoring studies.

Biggar M.A.,Wesley Hospital | Biggar M.A.,Middlemore Hospital Counties Manukau District Health | Kerr K.M.,Sullivan and Nicolaides Pathology | Erzetich L.M.,Wesley Hospital | Bennett I.C.,Wesley Hospital
Breast Journal | Year: 2012

Columnar cell change with atypia (CCCA) is a relatively recently recognized pathologic breast entity considered to be a risk factor for subsequent development of breast carcinoma. The aim of this study was to investigate the significance of finding CCCA on breast core biopsy, by establishing the frequency of other breast pathology on subsequently performed surgical excision specimens. All cases with CCCA as the most advanced lesion on core biopsy were reviewed. After excision, another advanced proliferative lesion was identified in 17 (33%) patients, including three patients (6%) with in situ or invasive carcinoma. An additional five patients (10%) were concurrently diagnosed with primary breast carcinoma at other sites. These findings indicate that when CCCA is found on core biopsy, open surgical biopsy of the relevant area should be performed and that workup of both breasts should be undertaken to exclude coexistent breast carcinoma at alternative sites. © 2012 Wiley Periodicals, Inc.

A Helicobacter pylori-negative young Japanese man with dyspeptic symptoms suffered from a diffuse erosive gastroduodenitis and multiple superficial ulcerations. Histology and electron microscopic examinations on the biopsy specimens revealed the presence of multiple unidentified intralesional and intracellular coccoid microorganisms in the pathological gastroduodenal mucosa. Microaerophilic and anaerobic Gram-negative coccoid and filamentobacillary bacteria were cultured from the gastric aspirate. The triple therapy containing tetracycline for 14 days followed by 4 months treatment with omeprazole resulted in the resolution of the gastroduodenal pathology. The question, therefore, was raised regarding a possible role for the cultured coccoid bacteria in the pathogenesis. 16S rRNA gene sequence analysis of the isolated Gram-negative coccoid bacteria revealed a close relationship with Haemophilus haemolyticus. The unidentified coccoid microorganisms and cultured X and V factors independent coccoid bacteria, however, shared similar phenotypic, microbiological and pathological characteristics to the novel Gram-negative Streptococcaceae: Okadaella gastrococcus.©2014 BMJ Publishing Group. All rights reserved.

Ahmed A.H.,University of Queensland | Gordon R.D.,University of Queensland | Taylor P.,University of Queensland | Ward G.,Sullivan and Nicolaides Pathology | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Background: The most popular screening test for primary aldosteronism (PAL) is the plasma aldosterone to renin ratio (ARR). Medications, dietary sodium, posture, and time of day all affect renin and aldosterone levels and can result in false-negative or -positive ARR if not controlled. Opinions are divided on whether β-adrenoreceptor blockers significantly affect the ARR. Methods: Normotensive, nonmedicated male volunteers (n = 21) underwent measurement (seated, midmorning) of plasma aldosterone (by HPLC-tandem mass spectrometry), direct renin concentration (DRC), renin activity (PRA), cortisol, electrolytes, and creatinine and urinary aldosterone, cortisol, electrolytes, and creatinine at baseline, and after 1 wk (25 mg daily) and 4 wk (50 mg daily for three additional weeks) of atenolol. Results: Compared with baseline, levels of aldosterone, DRC, and PRA were lower (P<0.001) after both 1 and 4 wk [median (25-75th percentiles): baseline, 189 (138-357) pmol/liter, 40 (30-46) mU/liter, and 4.6 (2.7-5.8) ng/ml · h; 1 wk, 166 (112-310) pmol/liter, 34 (30-40) mU/liter, and 2.6 (2.0-3.1) ng/ml · h; 4 wk, 136 (97-269) pmol/liter, 16 (13-23) mU/liter, and 2.1(1.7-2.6) ng/ml · h, respectively]. ARR was significantly higher after 1 wk compared with baseline when calculated using PRA [61 (30-73) vs. 65 (44-130), P<0.01] but not DRC [5 (4-7) vs. 5 (4-8)]. At 4 wk, ARR calculated by both PRA[78 (49-125)]and DRC[8 (6-14)] were significantly higher (P<0.001)compared with baseline,and cortisol levels were significantly lower [92 (68-100) vs. 66 (48-91) ng/ml, P < 0.01]. There were no changes in plasma sodium, potassium, creatinine, or any urinary measurements. Conclusion: β-Blockers can significantly raise the ARR and thereby increase the risk of false positives during screening for PAL. Copyright © 2010 by The Endocrine Society.

Ahmed A.H.,University of Queensland | Gordon R.D.,University of Queensland | Taylor P.J.,University of Queensland | Ward G.,Sullivan and Nicolaides Pathology | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Background: The most popular screening test for primary aldosteronism is plasma aldosterone/renin ratio (ARR). Because both estrogen and progesterone affect aldosterone and renin levels, we studied effects of two contraceptives commonly used in our population, one oral and one subdermal, on ARR, measuring renin as both direct renin concentration (DRC) and plasma renin activity (PRA). Methods: Normotensive, healthy women underwent measurement (seated, midmorning) of plasma aldosterone, DRC, PRA, electrolytes, and creatinine and urinary aldosterone, cortisol, electrolytes, and creatinine at baseline (menses) and after either 1) 3 wk treatment with oral ethinylestradiol plus drospirenone (n=17) or 2) 1wk and 6wk treatment with subdermal etonogestrel (n = 15), a third-generation progestin. Results: Treatment with oral ethinylestradiol plus drospirenone was associated with significant increases in aldosterone [median (range) at baseline = 131 (85-590) pmol/liter; at 1 wk, 200 (130-784) pmol/liter; and at 3 wk, 412 (199-1010) pmol/liter (P < 0.001, Friedman test)] and PRA [2.1 (1.2-4.7), 3.6 (1.5-7.1), and 4.9 (1.5-10.8) ng/ml·h, P < 0.001] but decreases in DRC [22 (11-36), 21 (8.7-41), and 14 (8.5-39) mU/liter, P < 0.01] leading to increases in ARR calculated by DRC [6.6 (3.3-31.3), 10.9 (5.2-58.9), and 29.8 (5.1- 88.5), P<0.001]. There were no significant changes inARR calculated by PRA, plasma electrolytes and creatinine, and all urinary measurements. In contrast, treatment with subdermal etonogestrel was associated with no significant changes in PRA, DRC, aldosterone, or ARR at either 1 or 6 wk. Conclusion: The combined oral contraceptive ethinylestradiol plus drospirenone is capable of significantly increasing ARR with risk of false-positive results during screening for primary aldosteronism, but only if DRC is used to calculate the ratio. Subdermal etonogestrel had no effect on ARR after 6 wk. Copyright © 2011 by The Endocrine Society.

Ahmed A.H.,University of Queensland | Gordon R.D.,University of Queensland | Taylor P.J.,University of Queensland | Ward G.,Sullivan and Nicolaides Pathology | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Background: Because primary aldosteronism is not uncommon, specifically treatable and in some cases curable, and carries higher risks for cardiovascular morbidity and mortality than essential hypertension, screening hypertensive patients for its presence by measuring aldosterone to renin ratio (ARR) is increasingly common. A significantly higher false-positive ARR rate for women than men, resulting in unnecessary suppression tests has previously been reported. Methods: Using a new, highly accurate aldosterone assay and both of the currently widely used renin assays, ARR was measured in 19 normal, ovulating women at three time points in the menstrual cycle and compared with single measurements in 21 normal males of similar age. Results: ARRs in males were possibly too well down in the current normal range. Although normotensiveandnormokalemic, twowomenhadraised ARRs in the luteal phase but only when direct renin concentration (DRC) was used. Their DRC levels were low at all sampling times [despite midrange plasma renin activity levels], whereas their progesterone and aldosterone levels were highest for the group. Saline suppression testing, performed in one of them, showed normal aldosterone suppressibility. Conclusion: False-positive ARRs in normal women during the luteal phase only when DRC is used may explain the higher incidence of false-positive ARRs in hypertensive women than men and suggest the following: 1) plasma renin activity is preferable to DRC in determination of ARR and 2) new reference ranges for ARR that take into account gender and sex hormone levels are required. Copyright © 2011 by The Endocrine Society.

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