34 research outputs found

    Le Fort Colpocleisis : re-visited and re-proposed

    Get PDF
    A case of an elderly woman suffering from severe genital prolapse is presented. This was so severe that her daily everyday activities became significantly impeded. This was a significant limitation to an individual who could otherwise manage independently of family or institutional help. Major surgical procedures (vaginal hysterectomy) are associated with significant risks in these elderly and frail women.1 Utero-vaginal prolapse is never a life-threatening condition and the surgeon is faced with the dilemma of whether to recommend this procedure, with this risk, to restore her mobility.peer-reviewe

    The paradox of pregnancy : an update on the immunology of early pregnancy

    Get PDF
    Pregnancy is an altered physiological state where an organism essentially foreign to the individual carrying it, grows, develops and at an appropriate time probably initiates a series of signals which lead to its safe expulsion from the woman's body. The immunological changes which allow this process are unique to pregnancy. Recent work in this field has led to a further understanding of the changes which operate to adapt the woman to the pregnant state. The concept that has developed over the years is one where a number of factors exert their effect both at the systemic but mostly at the local uterine level to modulate the immune response which will then refrain from mounting an inflammatory response against the invading trophoblast. The main protagonists of this immunomodulation are embryonic factors, uterine (endometrial) NK cells and, of course, the hormone progesterone. Progress has been made from the original observations of miscarriage rates in HLA sharing couples and with the possibility of research in couples undergoing IVF cycles, factors are being identified which initiate immunomodulation. Once implantation occurs the endometrial NK cells which are abundant from the late luteal phase are activated to control trophoblastic invasion and enhance the changes in blood vessels which allow for adequate feto-maternal perfusion. The immune response is controlled by PIBF under the influence of progesterone to bias towards a humoral response and suppress a cytotoxic response. All these processes are prone to fail at times and the clinical manifestation of such a failure is miscarriage along with other obstetric complications such as intra-uterine growth retardation, pre-eclampsia and placental abruption. Progress in the understanding of the immunological processes which protect pregnancy will help in elucidating the mechanisms whereby these processes fail. A consequence of this should be the explanation of those cases as yet classified as unexplained recurrent miscarriage. The literature indicates that the prognosis for this group of patients is not as encouraging as one would hope and that progress in this area is eagerly awaited by both patients and doctors working in this field.peer-reviewe

    Extensive Pulmonary Embolism in late pregnancy associated with Anticardiolipin Antibodies

    Get PDF
    The leading cause of morbidity and mortality during pregnancy and the puerperium is venous thromboembolism. Though uncommon, the risk is five times higher in a pregnant woman than in a non-pregnant woman of similar age.1,2 In pregnancy, all three underlying factors for venous thrombosis are present: hypercoagulability, venous stasis and vascular damage (Virchow's triad). Of these, the most constant predisposing factor is increasing venous stasis due to the pressure of the gravid uterus on the pelvic vasculature. In addition the presence of a thrombophilia, (congenital or acquired) will increase this risk substantially. During pregnancy hypercoagulability is a physiological preparation for the haemostatic challenge of delivery. There are increases in procoagulant factors, such as von Willebrand factor, factor VIII, factor V, and fibrinogen together with an acquired resistance to activated protein C and a reduction in protein S. Increases in plasminogen activator inhibitors impair fibrinolysis. The third factor of this triad, vascular damage, is a possible complication of trophoblastic invasion of the uterine spiral arterioles or of delivery.peer-reviewe

    Mycoplasma pneumonia : an unusual cause of acute myocarditis in childhood

    Get PDF
    Mycoplasma pneumoniae is primarily a respiratory pathogen but may affect exhibit a diverse range of presentations from asymptomatic infection to life threatening conditions. Myocarditis of varying severity is an unusual complication. We report a 6 year old with mycoplasma myocarditis, a rare age for such a presentation, and who responded well to treatment with no sequelae. Serological testing for Mycoplasma pneumoniae should be part of the routine work-up for myocarditis.peer-reviewe

    Biomarkers of pituitary adenoma behaviour

    Get PDF
    The pathological behaviour of pituitary adenomas (PAs) is complex and difficult to predict. In this study, the proliferation marker, Ki-67, pituitary tumour transforming gene (PTTG), vascular endothelial growth factor (VEGF), cyclin D1, c-MYC and pituitary adenylate cyclase-activating peptide (PACAP) protein expression were analyzed using immunohistochemistry in 74 PA samples (48 non-functional PAs, 26 functional PAs) and correlated with tumour characteristics including size, extension and tumour behaviour patterns. Correlation of protein marker expression with clinical characteristics yielded significant results. A correlation between PTTG expression and age at diagnosis, tumour size, tumour regrowth and Ki-67 was observed. Cyclin D1 and c-MYC also showed significant correlations with gender, tumour size, age at diagnosis and other protein markers. Significant differences in protein expression in the chosen markers were also observed between different tumour types, between patients treated pre-operatively with somatostatin analogues and in tumours with different intensity on MR imaging). Significant correlations were also observed between the markers themselves, with a possible direct link between two of the studied markers which substantiate data from other in vitro studies. Differences in protein localization were also analyzed to identify possible differences in biological behaviour arising in relation to nuclear vs cytoplasmic localization of the studied biomarkers. VEGF and PACAP similarly appeared interesting but exhibited few statistically significant correlations on detailed analysis. In conclusion, interesting and novel observations on the differences in expression of tumour markers studied are reported. Specifically, Ki-67 and PTTG appear to be very strongly correlated to tumour regrowth/recurrence and may be considered useful tools in predicting the proliferative potential of the resected tumours. Further data on the differential role of Cyclin D1 and cMYC in pituitary tumorigenesis and possibly tumour prognosis are presented.Principal author (MG, JV) was funded by the University of Malta Research funds (MEDRP02-05) and the Faculty of Medicine and Surgery (MDSIN08-22).RF is funded by the REACH HIGH Scholars Programme – Post-Doctoral Grant. The Research work disclosed in this publication is partially funded by the REACH HIGH Scholars Programme – Post Doctoral Grants. The grant is part-financed by the European Union, Operational Programme II – Cohesion Policy 2014 – 2020 “Investing in human capital to create more opportunities and promote the wellbeing of society” – European Social Fund.peer-reviewe

    The diagnosis and management of ectopic pregnancy presenting to Mater Dei Hospital between June 2019 and June 2020

    No full text
    The incidence of ectopic pregnancies has steadily increased over recent years and despite advances in treatment it still remains a major cause of maternal morbidity and mortality. The objective of this audit was to assess whether diagnosis and management is occurring as per international suggested guidance and practice. This study is a retrospective one using data collected from June 2019 to June 2020. All data were password protected and kept anonymous. No patient contact occurred. The standard cross referenced was the ‘April 2019 NICE Guideline on the Management of Ectopic Pregnancy’. Thirty-one ectopic pregnancies occurred between June 2019 and June 2020. Twenty-nine underwent surgical management and two medical. Six out of the 29 surgically managed patients were managed incorrectly. Twenty-four of the surgical cases were managed laparoscopically. Presence of a foetal heart rate remained undocumented in 21 out of 31 of cases. The results highlight the ease of access to emergency gynaecological services at Malta’s national hospital. However, this audit did highlight the discrepancy that can occur in examination in association with ectopic pregnancy. An inconsistency was noted in documentation. Additionally, a number of cases could have been offered and benefitted from different modes of management.Impact Statement What is already known on this subject? Ectopic pregnancy (EP) is an important cause of morbidity and mortality in mothers of childbearing age. The diagnostic method and appropriate management for EP has been extensively studied. Concrete- and evidence-based guidelines guide clinical management and improve morbidity and mortality. Local guidelines improve clinical outcome. What do the results of this study add? This study shows the impact of clinical outcome without a national guideline to guide management on a national level. Malta has one national hospital in which the local obstetrics and gynaecology department is run. The results of this study thus comprise of nationwide statistics on EP and its management. Ectopic pregnancies are managed without a local guideline in place. It also reflects the ease of access to health care in smaller countries. What are the implications of these findings for clinical practice and/or further research? The findings of this study have resulted in the production of a local guideline for the management of EP, as well as the introduction of a protocol for obtaining methotrexate for medical management. It has introduced new ultrasound machines and staff training to aid diagnostics. Further re-auditing will be carried out to analyse the impact a local guideline has on clinical practice at a national level

    RNA profiling of human growth hormone-secreting and non-functioning pituitary adenomas reveals novel and differentially expressed immune related genes

    No full text
    Pituitary neuroendocrine tumours (PitNETs) are broadly classified as non-functioning pituitary adenomas (NFPAs) and functional pituitary adenomas (FPAs) which include growth hormone secreting adenomas (GHPAs). Since the role of the immune system in PitNET pathogenesis is still poorly understood, we employed RNA-sequencing technology to unravel differentially expressed genes in GHPAs and NFPAs. Here we present an RNA-sequencing workflow of GHPAs (n=3) and NFPAs (n=7) which revealed a total of 7945 differentially expressed genes. Reactome, Gene Ontology and KEGG pathway analysis further revealed 57 genes involved in immune regulation. These genes fell into functional categories of chemokines, cytokines, interleukins, signal transduction and adhesion molecules. 6 immune genes including GATA3, CCL3, and CXCL9 were selected for further validation by qRT-PCR in 14 additional PitNET samples. A number of possible pathways implicated in PitNET functioning were also highlighted. The most significant were ‘T 1 and T 2 cell differentiation’, ‘cytokine-cytokine receptor pathway’, and ‘chemokine receptors bind chemokines’. Through our findings, we highlight distinct gene expression profiles in NFPAs and GHPAs and suggest that some of these genes could be considered as novel PitNET diagnostic markers for these two subtypes. We are currently validating these novel markers by immunohistochemistry in an array of PitNET subtypes.peer-reviewe

    Expression of canonical Wnt proteins and survivin in pituitary tumours

    Get PDF
    Wnt developmental pathways, have been implicated in a number of cancers. Wnt signaling proteins activate the B-catenin transcription factor which induces transcription of the oncogenes Cyclin D1 and Myc (Luo et al. 2007). Elston et al. (2008) found that Wnt inhibitors were down-regulated in pituitary tumours. Overexpression of Survivin, an inhibitor of apoptosis,correlates with poor prognosis and drug resistance (Altieri 2003, Ghosh et al. 2007). Survivin also interacts directly with the aryl hydrocarbon receptor – interacting protein (AIP) mutations of which have been linked with increased susceptibility to pituitary tumour development (Kang & Altieri 2006). The aim of this study was to analyze the expression of B-catenin, Cyclin D1, Myc and Survivin in 40 pituitary adenomas (30 non-functional, 7 acromegalic, 2 prolactinomas, 1 Cushing’s) collected at transphenoidal surgery and 6 normal controls using immunohistochemistry. The results indicate that B-catenin is membrane bound with no difference between normal and tumour tissue, although smaller tumours had higher expression (P<0.05). Cyclin D1 and Myc expression was nuclear and higher in tumour vs normal tissue (P<0.05). Myc expression also increased with lower age at diagnosis (P<0.001, R=0.361) while Cyclin D1 expression was higher in males than in females (P<0.05). Female patients also had overall younger age at diagnosis (P<0.05) and smaller tumours. Expression of survivin was very low in tumours and absent in normal controls. Therefore, involvement of the canonical Wnt pathway appears to be low, since B-catenin was not found located in the nucleus but Myc and Cyclin D1 proteins may play an important role in early pituitary tumorigenesis. Survivin appears to play a minor role owing to its almost complete absence in tumours with <1% of cells showing nuclear staining. Further analysis of the roles of Myc and Cyclin D1 in pituitary tumorigenesis is required.peer-reviewe

    A role for the mitochondrial protein Mrpl44 in maintaining OXPHOS capacity

    No full text
    We identified Mrpl44 in a search for mammalian proteins that contain RNase III domains. This protein was previously found in association with the mitochondrial ribosome of bovine liver extracts. However, the precise Mrpl44 localization had been unclear. Here, we show by immunofluorescence microscopy and subcellular fractionation that Mrpl44 is localized to the matrix of the mitochondria. We found that it can form multimers, and confirm that it is part of the large subunit of the mitochondrial ribosome. By manipulating its expression, we show that Mrpl44 may be important for regulating the expression of mtDNA-encoded genes. This was at the level of RNA expression and protein translation. This ultimately impacted ATP synthesis capability and respiratory capacity of cells. These findings indicate that Mrpl44 plays an important role in the regulation of the mitochondrial OXPHOS capacity.status: publishe
    corecore