• Long-term quality-of-life outcome after mesh sacrocolpopexy for vaginal vault prolapse.

      Thomas, Arun Z; Giri, Subhasis K; Cox, Ann-Marie; Creagh, Tom; Department of Urology and Renal Transplantation, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland. arunthomas75@gmail.com (2009-12)
      To evaluate the long-term outcome of mesh sacrocolpopexy (MSC, which aims to restore normal pelvic floor anatomy to alleviate prolapse related symptoms) and its effect on patient's quality of life, as women with vaginal vault prolapse commonly have various pelvic floor symptoms that can affect urinary, rectal and sexual function.
    • Loss of chromosome 1p/19q in oligodendroglial tumors: refinement of chromosomal critical regions and evaluation of internexin immunostaining as a surrogate marker.

      Buckley, Patrick G; Alcock, Leah; Heffernan, Josephine; Woods, Jack; Brett, Francesca; Stallings, Raymond L; Farrell, Michael A; The Royal College of Surgeons in Ireland, Cancer Genetics, 2nd Floor York House, York Street, Dublin, Dublin 2, Ireland. pbuckley@rcsi.ie (2011-03)
      Loss of chromosome 1p/19q in oligodendrogliomas represents a powerful predictor of good prognosis. Expression of internexin (INA), a neuronal specific intermediate filament protein, has recently been proposed as a surrogate marker for 1p/19q deletion based on the high degree of correlation between both parameters in oligodendrogliomas. The aim of this study was to assess further the diagnostic utility of INA expression in a set of genetically well-characterized oligodendrogliomas. On the basis of a conservative approach for copy number determination, using both comparative genomic hybridization and fluorescent in situ hybridization, INA expression as a surrogate marker for 1p/19q loss had both reduced specificity (80%) and sensitivity (79%) compared with respective values of 86% and 96% reported in the previous report. The histologic interpretation and diagnostic value of INA expression in oligodendrogliomas should therefore be assessed with greater caution when compared with 1p/19q DNA copy number analysis. In addition, DNA copy number aberrations of chromosomes 10, 16, and 17 were detected exclusively in 1p/19q codeleted samples, suggesting that other regions of the genome may contribute to the 1p/19q-deleted tumor phenotype inthese samples.
    • Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer.

      Furlong, Fiona; Fitzpatrick, Patricia; O'Toole, Sharon; Phelan, Sine; McGrogan, Barbara; Maguire, Aoife; O'Grady, Anthony; Gallagher, Michael; Prencipe, Maria; McGoldrick, Aloysius; et al. (2012-04)
      Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3' UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3'-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3' UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict paclitaxel responses in women presenting with high-grade serous EOC.
    • Low predictive value of positive transplant perfusion fluid cultures for diagnosing postoperative infections in kidney and kidney-pancreas transplantation.

      Cotter, Meaghan P; Smyth, Elizabeth; O'Gorman, Joanne; Browne, Sarah; Hickey, David P; Humphreys, Hilary; Department of Microbiology, Beaumont Hospital, Dublin, Ireland. mcotter@mater.ie (2012-12)
      Infection following transplantation is a cause of morbidity and mortality. Perfusion fluid (PF) used to preserve organs between recovery and transplantation represents a medium suitable for the growth of microbes. We evaluated the relevance of positive growth from PF sampled before the implantation of kidney or kidney-pancreas (KP) allografts.
    • Low total cortisol correlates closely with low free cortisol in traumatic brain injury and predicts mortality and long-term hypopituitarism

      Hannon, M J; Crowley, R K; Behan, L A; O'Sullivan, E P; Rogers, B; Rawluk, D; O'Dwyer, R; Agha, A; Thompson, C J (2011-06)
      Published data has demonstrated that low 0900h plasma total cortisol (PTC) in the acute phase following traumatic brain injury (TBI) predicts mortality. However, there is concern regarding the use of PTC to evaluate the pituitary-adrenal axis in acutely unwell patients due to potential discrepancies between PTC and plasma free cortisol (PFC) due to variations in corticosteroid binding globulin (CBG). We hypothesised that low PTC would correlate closely with PFC and would predict mortality and long-term hypopituitarism.100 patients (84 men, median age 33, range 18-75) were recruited on admission with TBI (mean GCS+/-SD = 8.59+/-4.2). Each patient had PTC and CBG measured on days 1, 3, 5, 7, and 10 following TBI. Results were compared with 15 patients admitted to ITU following vascular surgery. A PTC <300nmol/L in a patient in ITU was regarded clinically as inappropriately low. PFC was calculated for 25% of TBI samples and all control samples using Coolen's equation (1). TBI patients reattended for dynamic pituitary testing >6 months after TBI.All controls had PTC >500 nmol/L on day 1, and >300 nmol on days 3–10. By contrast, 78/100 TBI patients had at least one PTC <300 nmol/L.TBI patients in the lowest quartile of final PTC measurement had the highest mortality (p=0.0187). PTC correlated closely with PFC in both TBI patients (r=0.99, p<0.0001) and controls (r=0.99, p<0.0001). 32/79 (40.5%) of TBI survivors attended for dynamic pituitary testing. The median time to dynamic pituitary testing was 14 months (range 6–24 months). 15/32 (46.9%) underwent insulin tolerance testing, 9/32 (28.1%) underwent glucagon testing and 8/32 (25%) underwent short synacthen testing. 6/32 (18.8%) were ACTH deficient, of whom 5/6 (83.3%) previously had low PTC. 6/32 were GH deficient, all of whom previously had low PTC. One patient was gonadotropin deficient; he previously had low PTC. No patients were TSH or prolactin deficient. Overall, 12/32 (37.5%) had one or more pituitary hormone deficits. Lower mean PTC and final PTC were strongly associated with the development of chronic hypopituitarism (p = 0.049 and 0.015 respectively). There were no significant differences between those patients with acute or chronic hypopituitarism and those with no deficits in terms of age, initial GCS or CT appearances.PTC is an accurate surrogate marker of PFC in acutely unwell patients. Low PTC following TBI is predictive of mortality, and long-term hypopituitarism in TBI survivors.
    • Low-dose hydrocortisone (HC) replacement therapy is associated with improved bone remodeling balance in hypopituitary subjects

      Behan, L A; Kelleher, G; Hannon, M J; Brady, J J; Rogers, B; Tormey, W; Smith, D; Thompson, C J; McKenna, M J; Agha, A (2011-06)
      The effect of commonly used glucocorticoid replacement regimens on bone health in hypopituitary subjects is not well known. We aimed to assess the effect of 3 hydrocortisone (HC) replacement dose regimens on bone turnover in this group.10 hypopituitary men with severe ACTH deficiency were randomised in a crossover design to 3 HC dose regimens, Dose A (20mg mane, 10mg tarde), Dose B (10mg twice daily) and Dose C (10mg mane, 5mg tarde). Following 6 weeks of each regimen participants underwent fasting sampling of bone turnover markers.Data from matched controls were used to produce a Z score for subject bone formation and resorption markers and to calculate the bone remodeling balance (formation Z score-resorption Z score) and turnover index ((formation Z + resorption Z)/2). A positive bone remodeling balance with increased turnover is consistent with a favourable bone cycle. Data are expressed as median (range).The Pro Collagen Type 1 Peptide (PINP) bone formation Z-score was significantly increased in Dose C, (1.805 (-0.6-10.24)) compared to Dose A (0.035 (-1.0-8.1)) p<0.05 while there was no difference in the C-terminal crosslinking telopeptide (CTx) resorption Z score. The bone remodeling balance was significantly lower for dose A -0.02 (-1.05-4.12) compared to dose C 1.13 (0.13-6.4) (p<0.05). Although there was a trend to an increased bone turnover index with the lower dose regimen, this was not statistically significant.Low dose HC replacement (10mg mane/5 mg tarde) was associated with increased bone formation and improved bone remodeling balance which is associated with a more favourable bone cycle. This may have a long term beneficial effect on bone health.
    • Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.

      Gabardi, Steven; Catella, Jennifer; Martin, Spencer T; Perrone, Ronald; Chandraker, Anil; Magee, Colm C; McDevitt-Potter, Lisa M; Abdominal Organ Transplant Clinical Specialist–Departments of Transplant Surgery and Pharmacy Services, and the Renal Division, Brigham and Women's Hospital, Boston, MA, USA. sgabardi@partners.org (2011-09)
      To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation.
    • Male fertility in cystic fibrosis.

      Chotirmall, S H; Mann, A K; Branagan, P; O'Donohoe, C; Lyons, A M; Flynn, M G; Gunaratnam, C; O'Neill, S J; McElvaney, N G; Respiratory Research Division, Education & Research Centre, Beaumont Hospital, Dublin. schotirmall@rcsi.ie (2011-04-05)
      Infertility rates among males with cystic fibrosis (CF) approximate 97%. No information is currently available within Ireland determining an understanding of fertility issues and the best methods of information provision to this specialized group. This study aimed to determine understanding and preferred approaches to information provision on fertility issues to Irish CF males. A Descriptive Study utilizing prospective coded questionnaires was mailed to a male CF cohort (n=50). Sections included demographics, fertility knowledge & investigation. Response rate was 16/50 (32%). All were aware that CF affected their fertility. More than two-thirds (n=11) were able to provide explanations whilst only one-third (n=5) provided the correct explanation. Significant numbers stated thoughts of marriage and a future family. Half have discussed fertility with a healthcare professional (HCP). Mean age of discussion was 21.9 years. One third preferred an earlier discussion. The commonest first source for information was written material which was also the preferred source. Three-quarters requested further information preferring again, written material. Significant gaps in sex education of Irish CF males exist. Discussion should be initiated by HCPs and centre-directed written material devised to address deficiencies.
    • Male lupus: a diagnosis often delayed--a case series and review of the literature.

      Ambrose, N L; Kearns, G; Mohammad, A; Rheumatology Department, Beaumont Hospital, Dublin, Ireland. nambrose2001@yahoo.co.uk (2011-03)
      Systemic lupus erythematosus (SLE) is an auto-immune disease that is characterised by autoantibody production. Male lupus is rare, apart from at either end of the age spectrum.
    • Male lupus: a diagnosis often delayed--a case series and review of the literature.

      Ambrose, N L; Kearns, G; Mohammad, A; Rheumatology Department, Beaumont Hospital, Dublin, Ireland., nambrose2001@yahoo.co.uk (2012-02-01)
      INTRODUCTION: Systemic lupus erythematosus (SLE) is an auto-immune disease that is characterised by autoantibody production. Male lupus is rare, apart from at either end of the age spectrum. AIM: In this series, we review the histories of six male lupus patients attending our service. RESULTS: Our patients presented in middle age and tended to develop haematological abnormalities, renal involvement and neurological manifestations which preceded the onset of their skin and joint complaints. Our patients accrued damage rapidly and overall did badly. They tended to respond sub-optimally to standard treatments. These cases highlight the need an increased awareness that male SLE patients present with a wide variety of symptoms, and that they accrue damage quickly. There is a need for timely diagnosis and appropriate initiation of treatment. This may help avoid preventable organ damage and increase the survival of men with SLE.
    • Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers.

      Campbell, E; Kennedy, F; Russell, A; Smithson, W H; Parsons, L; Morrison, P J; Liggan, B; Irwin, B; Delanty, N; Hunt, S J; et al. (2014-09)
      Antiepileptic drug (AED) exposure during pregnancy increases the risk of major congenital malformations (MCMs). The magnitude of this risk varies by AED exposure. Here we provide updated results from the UK Epilepsy and Pregnancy Register of the risk of MCMs after monotherapy exposure to valproate, carbamazepine and lamotrigine.
    • Malignant melanoma and breast carcinoma: a bidirectional correlation.

      Ho, W L; Comber, H; Hill, A D K; Murphy, G M; Department of Dermatology, Beaumont Hospital, Dublin 9, Ireland, drwlho@yahoo.com. (2009-03-05)
      BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.
    • Malignant melanoma and breast carcinoma: a bidirectional correlation.

      Ho, W L; Comber, H; Hill, A D K; Murphy, G M; Department of Dermatology, Beaumont Hospital, Dublin 9, Ireland. drwlho@yahoo.com (2012-02-01)
      BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.
    • Malignant otitis externa: An Australian case series.

      Royal College of Surgeons Ireland, Otolaryngology, Beaumont Hospital, Dublin,, Ireland. (2012-02-01)
      OBJECTIVES: To establish a clinicopathological profile of malignant otitis externa (MOE) in an Australian tertiary referral institution. STUDY DESIGN: Retrospective cohort outcomes study. METHODS: 24 patients were identified with MOE between January 1998 and July 2007. Patients were classified into Radiological Grades I-IV. Laboratory investigations Including C-reactive protein (CRP), white cell count (WCC), glycosylated haemoglobin (HBA1c) and average glucose level over admission were recorded. RESULTS: Radiological Grade was significantly associated with duration of therapy (rank correlation 0.57, p = 0.004). CRP was a useful indicator confirming disease resolution. Diabetics with MOE had elevated average blood sugar levels during their Hospital admission (p < 0.001) and had poor overall glycaemic control represented by Elevated HBA1c scores (p < 0.001). CONCLUSIONS: Malignant otitis externa is a rare disease, which is best managed in a multidisciplinary team setting. This practical grading system can be used to predict the duration of therapy at time of diagnosis, which enables the efficient utilisation of Hospital resources. Poorly controlled diabetics are more susceptible to developing. MOE than diabetics with satisfactory glycaemic control and may represent a subgroup of more brittle diabetics. CRP combined with appropriate clinical and radiological investigations is useful in assessing disease resolution.
    • The management of amyotrophic lateral sclerosis.

      Phukan, Julie; Hardiman, Orla; Dept. of Neurology, Beaumont Hospital, and Trinity College Institute of Neuroscience, Dublin 9, Ireland. (2009-02)
      The terms amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND) refer to a condition characterized by motor system degeneration with relative preservation of other pathways. Although there have been advances in symptomatic treatment, ALS remains an incurable condition. Advances in ALS management prolong survival but simultaneously raise challenging ethical dilemmas for physicians, patients and their families. Here, we review current practice in the management of ALS including pharmacological treatment, nutritional management, respiratory care, and evolving strategies in the management of cognitive impairment.
    • Management of parenteral nutrition associated hyperglycaemia: A comparison of subcutaneous and intravenous insulin regimen

      Neff, K; Donegan, D; MacMahon, J; O’Hanlon, C; Keane, N; Agha, A; Thompson, C; Smith, D (Irish Medical Jorunal, 2014-05)
      PN is associated with significant hyperglycaemia, which may be detrimental to clinical outcome. There are few data on the management of this phenomenon outside of intensive care units. In our unit, we studied the efficacy of protocol-based intravenous insulin delivery as compared to subcutaneous insulin prescribed individually outside of the critical care setting. In a retrospective review over a two-year period, we compared patients with PN-associated hyperglycaemia who had received both modes of insulin therapy. A total of 122 who developed PN-associated hyperglycaemia were identified. Those on the intravenous insulin regimen were within glycaemic target for more time than those on the subcutaneous regimen (62% Vs 43%, p=0.008). We therefore conclude that outside of the critical care setting, intravenous insulin delivers better glycaemic control and should therefore be considered optimum therapy for patients with PN-associated hyperglycaemia.
    • Management of respiratory symptoms in ALS.

      Hardiman, Orla; HRB Clinician Scientist, Trinity College and Beaumont Hospital, Dublin, Ireland, orla@hardiman.net. (2011-03)
      Respiratory insufficiency is a frequent feature of ALS and is present in almost all cases at some stage of the illness. It is the commonest cause of death in ALS. FVC is used as important endpoint in many clinical trials, and in decision-making events for patients with ALS, although there are limitations to its predictive utility. There are multiple causes of respiratory muscle failure, all of which act to produce a progressive decline in pulmonary function. Diaphragmatic fatigue and weakness, coupled with respiratory muscle weakness, lead to reduced lung compliance and atelectasis. Increased secretions increase the risk of aspiration pneumonia, which further compromises respiratory function. Bulbar dysfunction can lead to nutritional deficiency, which in turn increases the fatigue of respiratory muscles. Early recognition of respiratory decline and symptomatic intervention, including non-invasive ventilation can significantly enhance both quality of life and life expectancy in ALS. Patients with respiratory failure should be advised to consider an advance directive to avoid emergency mechanical ventilation.
    • Management of respiratory symptoms in ALS.

      Hardiman, Orla; HRB Clinician Scientist, Trinity College and Beaumont Hospital, Dublin, Ireland. , orla@hardiman.net (2012-02-01)
      Respiratory insufficiency is a frequent feature of ALS and is present in almost all cases at some stage of the illness. It is the commonest cause of death in ALS. FVC is used as important endpoint in many clinical trials, and in decision-making events for patients with ALS, although there are limitations to its predictive utility. There are multiple causes of respiratory muscle failure, all of which act to produce a progressive decline in pulmonary function. Diaphragmatic fatigue and weakness, coupled with respiratory muscle weakness, lead to reduced lung compliance and atelectasis. Increased secretions increase the risk of aspiration pneumonia, which further compromises respiratory function. Bulbar dysfunction can lead to nutritional deficiency, which in turn increases the fatigue of respiratory muscles. Early recognition of respiratory decline and symptomatic intervention, including non-invasive ventilation can significantly enhance both quality of life and life expectancy in ALS. Patients with respiratory failure should be advised to consider an advance directive to avoid emergency mechanical ventilation.
    • Manifesto for the current understanding and management of traumatic brain injury-induced hypopituitarism.

      Tanriverdi, F; Agha, A; Aimaretti, G; Casanueva, F F; Kelestimur, F; Klose, M; Masel, B E; Pereira, A M; Popovic, V; Schneider, H J; et al. (2011)
      Traumatic brain injury (TBI)-induced hypopituitarism remains a relevant medical problem, because it may affect a significant proportion of the population. In the last decade important studies have been published investigating pituitary dysfunction after TBI. Recently, a group of experts gathered and revisited the topic of TBI-induced hypopituitarism. During the 2-day meeting, the main issues of this topic were presented and discussed, and current understanding and management of TBI-induced hypopituitarism are summarized here.
    • Massive hepatic cyst presenting as right-sided heart failure.

      O'Connor, A; Lee, M; McEntee, G; McNamara, D A; Department of Surgery, Beaumont Hospital, Dublin 9, Ireland, aoconnor@rcsi.ie. (2010-01-30)
      A 70-year-old woman presented with clinical features of right heart failure. Cardiopulmonary investigations included an echocardiogram, which showed a hepatic cyst compromising venous return and affecting right atrial filling and a CT abdomen showed a 15.5 x 11.5 cm-cystic mass involving the right hepatic lobe and compressing the right atrium. Percutaneous drainage of the cyst was performed. This led to complete resolution of symptoms but these recurred as the fluid re-accumulated. Subsequent definitive treatment with excision of the cyst was undertaken with symptomatic cure. This case is the first report of a hepatic cyst presenting as right heart due to compression of the right atrium.