Molinari E.,Livet S.r.l. |
Molinari E.,University of Turin |
Mirabelli M.,Endocrinology Laboratory |
Raimondo S.,University of Turin |
And 5 more authors.
Reproductive BioMedicine Online
This paper reports a case of recurrent miscarriage in a patient affected by a variant phenotype of sperm macrocephaly syndrome (SMS). SMS is usually related to specific sperm characteristics (large head, multiple tail) and homozygous mutations in the aurora kinase C gene (AURKC). However, the present case observed large-headed spermatozoa with no flagellar abnormalities and no mutations detectable by AURKC sequencing. Furthermore, the patient had repeatedly conceived by intracytoplasmic sperm injection, but pregnancy always aborted. This study performed morphological analysis (Papanicolau staining), annexin V/propidium iodide staining, sperm chromatin structure assay (SCSA), fluorescence in-situ hybridization (FISH) and transmission electron microscopy. This study observed large-headed, mono-tailed, mono-centriolar spermatozoa characterized by abnormal chromatin and swollen mitochondria. SCSA revealed a high ratio of late apoptotic cells with fairly intact amount of DNA. The FISH analysis showed 100% disomy rate. As far as is known, this is the first study to include gene sequencing, TEM, cytogenetic analysis and sperm DNA fragmentation in a case of SMS and also to report recurrent miscarriage related to this specific condition. SMS may be associated with important abnormalities of the sperm subcellular structure and with disomy even in the absence of mutations in the AURKC coding sequence. Sperm macrocephaly syndrome (SMS) is a rare condition that affects spermatozoa and is related to infertility. It is characterized by a specific phenotype of large-headed, multi-tailed spermatozoa with an abnormal chromosomal status. A very few pregnancies have been obtained so far in SMS patients by means of IVF procedures. We present a case of SMS that differs from the classical syndrome as we observed large-headed spermatozoa without tail abnormalities. The affected patient had achieved three pregnancies following IVF, but all aborted. We carried out a detailed examination of the patient's spermatozoa-morphological, cytogenetic, DNA fragmentation and ultrastructural analysis-and we observed that his spermatozoa are characterized by a large head whose texture appears apoptotic, a single tail and a midpiece whose mitochondria appear swollen. The DNA content within the spermatozoa was altered, as well as the chromosomal status, suggesting that some error must have occurred during spermatogenesis. Interestingly, the genetic sequencing of the specific gene usually related to SMS syndrome (AURKC) revealed no mutations in our patient, suggesting that other genes may be involved in determining this syndrome. As far as is known, this is the first study in which spermatozoa of a SMS patient have been observed using morphological analysis, ultrastructural analysis, cytogenetic analysis and sperm DNA fragmentation analysis together. Moreover, it is believed that this is first report of recurrent miscarriage due to this specific syndrome. © 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. Source
HE4, CA125, the Risk of Malignancy Algorithm and the Risk of Malignancy Index and complex pelvic masses - A prospective comparison in the pre-operative evaluation of pelvic masses in an Australian population
Richards A.,Lifehouse Gynaecology Oncology Group |
Herbst U.,Lifehouse Gynaecology Oncology Group |
Manalang J.,Lifehouse Gynaecology Oncology Group |
Pather S.,Lifehouse Gynaecology Oncology Group |
And 10 more authors.
Australian and New Zealand Journal of Obstetrics and Gynaecology
Background Human epididymis protein 4 (HE4) has been proposed as a novel biomarker for the diagnosis of epithelial ovarian cancer. Using HE4 and CA125, the risk of malignancy algorithm (ROMA) has been shown to be effective in the stratification of epithelial ovarian cancer risk. Aims To determine the effectiveness of HE4 and ROMA in the diagnosis of malignancy of women presenting with a complex pelvic mass in an Australian population and to compare it with CA125 and the risk of malignancy index (RMI). Materials and Methods Prospective recruitment of women was conducted between October 2012 and March 2014 (n = 50). CA125 and HE4 serum concentrations were collected and stored for subsequent analysis. Sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV) were calculated for HE4, CA125, ROMA and the RMI. Receiver operating characteristic (ROC) area under the curves (AUC) were also calculated for comparison. Results There was a higher HE4 level in women with ovarian cancer compared with women with benign pathology (P = 0.008), and this observation was seen in benign versus stage 1 ovarian cancer women (P = 0.025). HE4 had a better specificity than CA125 for the diagnosis of ovarian cancer in all women (P = 0.022), and this effect was also observed in premenopausal women (P = 0.012). Furthermore, the ROC-AUC for HE4 was superior than CA125 in all women (P = 0.0451). The ROMA algorithm was not inferior to the RMI calculation in this population. Conclusions In an Australian population, HE4 and ROMA are useful in the diagnosis of epithelial ovarian cancer. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Source
Martin W.G.,St. Vincents Hospital Melbourne |
Galligan J.,Royal Hobart Hospital |
Simpson S.,University of Tasmania |
Greenaway T.,Clinical Endocrinology |
And 3 more authors.
Internal Medicine Journal
Background: Hyperglycaemia has been associated with adverse outcomes in several different hospital populations. Aim: The aim of this study was to investigate the relationship between admission blood glucose level (BGL) and outcomes in all patients admitted through the emergency department. Methods: This study was a retrospective observational cohort study from an Australian tertiary referral hospital. Patients admitted in the first week of each month from April to October 2012 had demographic data, co-morbidities, BGL, intensive care unit admission, length of stay and dates of death recorded. Factors associated with outcomes were assessed by multi-level mixed-effects linear regression. Results: Admission BGL was recorded for 601 admissions with no diagnosis of diabetes and for 219 admissions diagnosed with type 2 diabetes (T2DM). In patients with no diagnosis of diabetes, admission BGL was associated with in-hospital and 90-day mortality (P < 0.001). After multivariate analysis, BGL greater than 11.5mmol/L was significantly associated with increased mortality at 90 days (P < 0.05). In patients with T2DM increased BGL on admission was not associated with in-hospital or 90-day mortality but was associated with length of hospital stay (β: 0.22 days/mmol/L; 95% confidence interval 0.09-0.35; P < 0.001), although this association was lost on multivariable analysis. In patients with T2DM, increased coefficient of variation of BGL was also positively associated with length of hospital stay in an almost dose-dependent fashion (P < 0.001). Conclusion: Admission BGL was independently associated with increased mortality in patients with no diagnosis of diabetes. Glycaemic variability was associated with increased length of hospital stay in patients with T2DM. © 2015 Royal Australasian College of Physicians. Source
Tijero B.,University of the Basque Country |
Gomez-Esteban J.C.,University of the Basque Country |
Lezcano E.,University of the Basque Country |
Fernandez-Gonzalez C.,University of the Basque Country |
And 12 more authors.
Parkinsonism and Related Disorders
Objective: The aim of this study was to analyze autonomic function and cardiac sympathetic innervation in symptomatic and asymptomatic carriers of the E46K alpha-synuclein gene (SNCA) mutation. Patients and methods: Autonomic function tests were performed in six patients, four of whom were symptomatic carriers (ages: 46, 59, 52 and 28-years) and two who were asymptomatic carriers (ages: 52 and 29 years). Autopsy studies were performed on an additional two symptomatic carriers not eligible for autonomic testing. Patients completed the SCOPA autonomic questionnaire, and underwent the head-up tilt test accompanied by measurements of plasma norepinephrine. Valsalva maneuver and deep breathing tests, along with recording of sympathetic skin response (SSR) and cardiac MIBG scintigraphy were carried out. Myocardial tissue sections removed from the two autopsied cases were subjected to routine histological staining and immunohistochemical processing with monoclonal antibodies against tyrosine hydroxylase and alpha-synuclein. Results: Both the four symptomatic and the older asymptomatic carriers reported abnormalities in the SCOPA questionnaire and had markedly diminished cardiac MIBG uptake. Plasma norepinephrine in the supine and tilted positions was normal in all subjects. Only one patient had significant orthostatic hypotension. There was a complete absence of tyrosine hydroxylase immunostaining in the myocardium of the two autopsied cases. Interpretation: We have found imaging and histological evidence of cardiac sympathetic denervation in symptomatic and asymptomatic carriers of the E46K alpha-synuclein gene mutation. The sympathetic denervation appears to be organ-specific, with selective affectation of the heart given that plasma norepinephrine levels and blood pressure were normal. © 2012 Elsevier Ltd. Source
PhD student in UQ's School of Agriculture and Food Science (SAFS) Alyce Swinbourne is tickling the rumps of sleepy female southern hairy-nosed wombats as a prelude to collecting their wombat wee into a tiny frypan. "People need to go when they wake up, and so do wombats," Alyce said. "This study uses knowledge of wombats' natural behaviour to collect urine samples in a non-invasive way with little stress to them. I simply pull out the frypan by the handle when they're finished." Alyce's classical conditioning methods have enabled her to collect close to 2500 urine samples —an approach believed to have never before attempted in a marsupial. The research has a serious purpose. Wombats have proved a notoriously difficult species for which to develop assisted breeding techniques (artificial insemination) in captive management. While she is working with the southern species, found widely in southern Australia, she hopes the work ultimately will assist in developing breeding programs to conserve their northern cousins—among the rarest land animals in the world. There are only 200 known northern hairy-nosed wombats in the wild, most at Epping Forest National Park near Clermont, Central Queensland. Floods in 2001 led to the translocation of a smaller "insurance" population in case of further natural disasters at the first site. "If we want to ensure their future, we need to develop assisted reproductive technologies to help in their recovery in reserve areas in the wild and this is where the scientific development of breeding programs comes in, based on better understanding of the animals' biology," she said. Alyce has worked with wombats over two breeding seasons at Safe Haven - AACE (Australian Animals Care and Education) sanctuary for Australian wildlife in Mt Larcom, Central Queensland. Associate Professor Steve Johnston and Dr Tamara Keeley of UQ's SAFS are supervising her research, and samples are being analysed at the Wildlife Endocrinology Laboratory at UQ's Gatton campus. Alyce is working with Dr Keeley and Associate Professor Johnston to develop new diagnostic techniques to analyse reproductive hormones. She is also observing wombat behaviour using infrared cameras, for six hours a day, for up to nine months, to gain a better understanding of the breeding behaviour. Professor Clive Phillips, Director of UQ's Centre for Welfare and Ethics is also providing expert advice. "I hope that the skills developed in this project will be transferable to other Australian marsupial species, such as koalas and gliders," Alyce said. Now living in Adelaide where her husband, Mike, is also undertaking a PhD, Alyce said she had had "a ball" during her studies, although it was financially quite challenging. During her studies she has been a finalist in UQ's Three Minute Thesis competition, attended a Reproduction conference in South Australia, a wildlife conference in Hobart and was awarded a SAFS Travel Scholarship to present her findings in Germany in August, 2016.