• An evaluation of the simultaneous use of the levonorgestrel-releasing intrauterine device (LNG-IUS, Mirena®) combined with endometrial ablation in the management of menorrhagia.

      Vaughan, D; Byrne, P; Department of Gynaecology, Beaumont Hospital, Dublin, Ireland. (2012-05)
      The objective of our study was to document the efficacy and possible complications in women who were treated for menorrhagia with the simultaneous use of endometrial ablation and the levonorgestrel-releasing intrauterine device. Women were offered this combined treatment if they complained of menorrhagia and needed contraception. A structured questionnaire was mailed to 150 women who had undergone this combined treatment; 105 (70%) returned a completed questionnaire. The mean duration of follow-up was 25 months (range 6-54 months). Following treatment, 53 women (50.5%) described their periods as being lighter than normal and 49 (46%) had become amenorrhoeic. Overall, 101 (96%) stated that they were satisfied with the treatment. Of the women, 95 (90.5%) said that the treatment had been a 'complete success'; eight (7.6%) 'partly successful' and two women (1.9%) said the treatment had been a 'failure'. One woman subsequently required a hysterectomy. This observational study supports the hypothesis that combined endometrial ablation and insertion of a levonorgestrel-releasing intrauterine device is an effective treatment for menorrhagia and has some advantages when compared with the individual use of these treatments.
    • Evaluation of Zinc-alpha-2-Glycoprotein and Proteasome Subunit beta-Type 6 Expression in Prostate Cancer Using Tissue Microarray Technology.

      Oʼhurley, Gillian; Oʼgrady, Anthony; Smyth, Paul; Byrne, Jennifer; Oʼleary, John J; Sheils, Orla; Watson, R William G; Kay, Elaine W; Department of Pathology, RCSI ERC Beaumont Hospital daggerDepartment of Histopathology, Trinity College Dublin double daggerUCD School of Medicine and Medical Science, UCD Conway Institute of Biomolecular and Biomedical Research, Universtity College Dublin, Ireland. (2010-07-23)
      Prostate cancer (CaP) is a significant cause of illness and death in males. Current detection strategies do not reliably detect the disease at an early stage and cannot distinguish aggressive versus nonaggressive CaP leading to potential overtreatment of the disease and associated morbidity. Zinc-alpha-2-glycoprotein (ZAG) and proteasome subunit beta-Type 6 (PSMB-6) were found to be up-regulated in the serum of CaP patients with higher grade tumors after 2-dimensional difference gel electrophoresis analysis. The aim of this study was to investigate if ZAG and PSMB-6 were also overexpressed in prostatic tumor tissue of CaP patients. Immunohistochemical analysis was performed on CaP tissue microarrays with samples from 199 patients. Confirmatory gene expression profiling for ZAG and PSMB-6 were performed on 4 cases using Laser Capture Microdissection and TaqMan real-time polymerase chain reaction. ZAG expression in CaP epithelial cells was inversely associated with Gleason grade (benign prostatic hyperplasia>G3>G4/G5). PSMB-6 was not expressed in either tumor or benign epithelium. However, strong PSMB-6 expression was noted in stromal and inflammatory cells. Our results indicate ZAG as a possible predictive marker of Gleason grade. The inverse association between grade and tissue expression with a rising serum protein level is similar to that seen with prostate-specific antigen. In addition, the results for both ZAG and PSMB-6 highlight the challenges in trying to associate the protein levels in serum with tissue expression.
    • Evidence for shared susceptibility to epilepsy and psychosis: a population-based family study.

      Clarke, Mary C; Tanskanen, Antti; Huttunen, Matti O; Clancy, Maurice; Cotter, David R; Cannon, Mary; Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland. maryclarke@rcsi.ie (2012-05-01)
      There is emerging evidence of an etiological overlap between a range of neurodevelopmental disorders, including schizophrenia and epilepsy. Here we investigate shared familial vulnerability to psychotic illness and epilepsy in a family-based study.
    • Evidence for unfolded protein response activation in monocytes from individuals with alpha-1 antitrypsin deficiency.

      Carroll, Tomás P; Greene, Catherine M; O'Connor, Catherine A; Nolan, Aine M; O'Neill, Shane J; McElvaney, Noel G; Respiratory Research Division, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland. tcarroll@rcsi.ie (2010-04-15)
      The hereditary disorder alpha-1 antitrypsin (AAT) deficiency results from mutations in the SERPINA1 gene and presents with emphysema in young adults and liver disease in childhood. The most common form of AAT deficiency occurs because of the Z mutation, causing the protein to fold aberrantly and accumulate in the endoplasmic reticulum (ER). This leads to ER stress and contributes significantly to the liver disease associated with the condition. In addition to hepatocytes, AAT is also synthesized by monocytes, neutrophils, and epithelial cells. In this study we show for the first time that the unfolded protein response (UPR) is activated in quiescent monocytes from ZZ individuals. Activating transcription factor 4, X-box binding protein 1, and a subset of genes involved in the UPR are increased in monocytes from ZZ compared with MM individuals. This contributes to an inflammatory phenotype with ZZ monocytes exhibiting enhanced cytokine production and activation of the NF-kappaB pathway when compared with MM monocytes. In addition, we demonstrate intracellular accumulation of AAT within the ER of ZZ monocytes. These are the first data showing that Z AAT protein accumulation induces UPR activation in peripheral blood monocytes. These findings change the current paradigm regarding lung inflammation in AAT deficiency, which up until now was derived from the protease-anti-protease hypothesis, but which now must include the exaggerated inflammatory response generated by accumulated aberrantly folded AAT in circulating blood cells.
    • Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress.

      Behan, Aine T; van den Hove, Daniel L A; Mueller, Lynn; Jetten, Marlon J A; Steinbusch, Harry W M; Cotter, David R; Prickaerts, Jos; Department of Psychiatry, Royal College of Surgeons in Ireland, RCSI Education, and Research Centre, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland., abehan@rcsi.ie (2012-02-01)
      Prenatal stress (PS) has been associated with an increased incidence of numerous neuropsychiatric disorders, including depression, anxiety, schizophrenia, and autism. To determine the effects of PS on hippocampal-dependent behaviour hippocampal morphology, we examined behavioural responses and hippocampal cytoarchitecture of a maternal restraint stress paradigm of PS in C57BL6 mice. Female offspring only showed a reduction in hippocampal glial count in the pyramidal layer following PS. Additionally, only PS females showed increased depressive-like behaviour with cognitive deficits predominantly in female offspring when compared to males. This data provides evidence for functional female-specific glial deficits within the hippocampus as a consequence of PS.
    • Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress.

      Behan, Aine T; van den Hove, Daniel L A; Mueller, Lynn; Jetten, Marlon J A; Steinbusch, Harry W M; Cotter, David R; Prickaerts, Jos; Department of Psychiatry, Royal College of Surgeons in Ireland, RCSI Education and Research Centre, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland. abehan@rcsi.ie (2011-01)
      Prenatal stress (PS) has been associated with an increased incidence of numerous neuropsychiatric disorders, including depression, anxiety, schizophrenia, and autism. To determine the effects of PS on hippocampal-dependent behaviour hippocampal morphology, we examined behavioural responses and hippocampal cytoarchitecture of a maternal restraint stress paradigm of PS in C57BL6 mice. Female offspring only showed a reduction in hippocampal glial count in the pyramidal layer following PS. Additionally, only PS females showed increased depressive-like behaviour with cognitive deficits predominantly in female offspring when compared to males. This data provides evidence for functional female-specific glial deficits within the hippocampus as a consequence of PS.
    • Evidence-based models of care for people with epilepsy.

      Fitzsimons, Mary; Normand, Charles; Varley, Jarlath; Delanty, Norman; Epilepsy Programme, Beaumont Hospital, Dublin, Ireland. (2012-02-01)
      Advances in medical science and technology, together with improved medical and nursing care, are continuously improving health outcomes in chronic illness, including epilepsy. The consequent increasing diagnostic and therapeutic complexity is placing a burgeoning strain on health care systems. In response, an international move to transform chronic disease management (CDM) aims to optimize the quality and safety of care while containing health care costs. CDM models recommend: integration of care across organizational boundaries that is supported with information and communication technology; patient self-management; and guideline implementation to promote standardized care. Evidence of the effectiveness of CDM models in epilepsy care is presented in this review article.
    • Evolution of DWI signal abnormalities after transient ischemic attack and minor ischaemic stroke

      Merwick, A; Callally, E L; Duggan, J; Dolan, E; Hannon, N; Kavangh, E C; Lawler, L; Marnane, M; Moroney, J T; Moynagh, M R; et al. (Karger, 2011-05)
      Background: Diffusion weighted imaging (DWI) signal abnormality after transient ischaemic attack (TIA) predicts early stroke, independently of other risk markers included in the ABCD3-I score. Early stroke recurrence detected on follow-up DWI after the acute-phase DWI may identify patients at high risk for subsequent clinicalstrokesstroke, cognitive impairment, and seizures. We aimed to determine the evolution of acute DWI lesions and rate of new ischaemic lesion (NIL) occurrence on follow-up DWI after TIA and minor stroke. Methods: Early DWI-detected stroke recurrence (defined as NILs on follow-up DWI one week after acute DWI) was identified in a prospective MRI study of TIA and minor stroke patients. Presence/absence of DWI lesion(s), topography, clinical variables, and clinical stroke recurrence by day 7 and 90 were recorded. Results: 87 patients were included, 65 TIA and 22 minor stroke. Study patients’ mean age was 68 years [Standard deviation 6], 64% male, mean ABCD2 score 4, mean ABCD3-I score 5 (TIA patients only). The median duration from symptom onset to acute (baseline) DWI was 2 days (Interquartile range 2-3) and to follow-up MRI was 10 days (IQR 8-12),with 7-day median interval between DWIs (IQR 5-9). 23/65 TIA patients (37.3% [95% CI 23.9-48.2]) had at least one DWI lesion at baseline. Early recurrent stroke occurred in 3.4% (3/87 patients) when defined clinically, compared to 6.9% [95% CI 2.6-14.4] (6/87) when defined by MRI (p<0.001). NILs were detected in 2/22 stroke patients 9.1% [95% CI 1.1-29.2] and 4/65 TIA patients 6.2% [95% CI 1.7-15.0]. In 60.9% [95% CI 38.5-80.3] TIA patients (14/23) with baseline DWI lesions, these were no longer detectable on early follow-up DWI. Discussion: Early follow-up DWI increased the identification of recurrent ischaemia compared to clinical evaluation alone. Early resolution of initial DWI lesions after TIA indicates the dynamic nature of ischaemic changes and importance of early MRI for risk stratification in practice.
    • Evolving issues in the prevention of surgical site infections.

      Quinn, A; Hill, A D K; Humphreys, H; Dept of Surgery, Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin. (2009-06)
      Surgical site infection is one of the more common causes of post-operative morbidity. Such infections contribute to prolonged recovery, delayed discharge and increasing costs to both patients and the health service. In the current climate increased emphasis is being placed on minimising the risks of acquiring or transmitting these nosocomial infections. This article reviews the current literature obtained from a Pubmed database search in relation to three specific aspects of surgical site infection: compliance with prophylactic antibiotics, post-discharge surveillance and novel methods for preventing surgical site infections. These topics represent areas where many institutions will find room for improvement in the prevention of surgical site infections. Tight adherence to prophylactic antibiotic guidelines, close followup of surgical wounds during and after hospital discharge, and attention to oxygenation status and the body temperature of patients may all prove to be useful adjuncts in significantly decreasing surgical site infections.
    • Examination of 12-lipoxygenase (12-LOX) as a therapeutic target in non-small cell lung cancer (NSCLC): Mechanisms controlling survival and induction of apoptosis following selective inhibition

      Cathcart, Mary Clare; Campbell, Vikki; Gately, Kathy; Cummins, Robert; Kay, Elaine; Pidgeon, Graham P; O'Byrne, Kenneth J (2011-06)
      Background: Platelet-type 12-LOX is an arachidonic acid metabolising enzyme resulting in the formation of 12(S)-HETE, which stimulates tumour cell adhesion, invasion and metastasis. This study aimed to examine the expression profile and role of this enzyme in NSCLC, and determine if it is a potential target for intervention. Methods: A panel of retrospective resected lung tumours was stained for 12-LOX expression by IHC. Levels of the 12-LOX metabolite, 12(S)-HETE, were examined in 50 NSCLC serum samples, and correlated with serum VEGF. A panel of NSCLC cell lines were treated with baicalein (10 uM), a selective inhibitor of 12-LOX, or 12(S)-HETE (100 ng/ml) and cell survival/proliferation examined by BrdU. Apoptosis following 12-LOX inhibition was examined by HCS and validated by FACS and DNA laddering. The effect of 12-LOX inhibition on NSCLC tumour growth and survival was examined in-vivo using an athymic nude mouse model. Gene alterations following 12-LOX inhibition in NSCLC cell lines were assessed by qPCR arrays and validated by RT-PCR. Transient transfection methods were used to examine the effects of 12-LOX overexpression in NSCLC cells. Results: 12-LOX expression was observed to a varying degree in human lung cancers of varying histological subtypes. 12(S)-HETE levels were correlated (p<0.05) with those of VEGF. Baicalein inhibited proliferation/survival in all cell lines, while 12(S)-HETE increased proliferation. 12-LOX inhibition increased apoptosis, indicated by a reduction in f-actin content and mitochondrial mass potential. Treatment with baicalein significantly reduced the growth of NSCLC tumours and increased overall survival in athymic nude mice. qPCR array data implicated a number of apoptosis/angiogenesis genes regulating these effects, including bcl-2, VEGF, integrin A2 and A4. 12-LOX overexpression resulted in an increase in VEGF secretion, confirming qPCR observations. Conclusions: 12-LOX is a survival factor/potential target in NSCLC, and correlated with angiogenic factor expression. Selective 12-LOX targeting may have clinical benefit for the future treatment.
    • Executive dysfunction is a negative prognostic indicator in patients with ALS without dementia.

      Elamin, M; Phukan, J; Bede, P; Jordan, N; Byrne, S; Pender, N; Hardiman, O; Trinity Institute of Neuroscience, Dublin, Ireland. marwaelamin08@gmail.com (2011-04-05)
      The prognostic implications of cognitive impairment in amyotrophic lateral sclerosis (ALS) are not established.
    • An exploration of nursing documentation of pressure ulcer care in an acute setting in Ireland.

      O Brien, J A Jordan; Cowman, S; Beaumont Hospital, Dublin, Ireland. juliejordanobrien@beaumont.ie (2012-02-01)
      OBJECTIVE: To explore the nature and quality of documented care planning for pressure ulcers in a large teaching hospital in the Republic of Ireland. METHOD: A mixed method design was used; this encompassed a descriptive survey that retrospectively evaluated nursing records (n=85) in two wards (orthopaedic and care of the older adult) and a focus group (n=13) that explored nurses' perspectives of the factors influencing concordance and the quality of nursing documentation. Only records of at-risk patients (Waterlow score of >10) were included. RESULTS: It was identified that 47% (n=40) were assessed as at high or very high risk of developing a pressure ulcer. Fifty-two patients (61%) had a weekly risk assessment, but 25% (n=21) had only one follow-up assessment. Only 45% (n=38) of charts had some evidence of documented care planning, and of those 53% (n=20) had no evidence of implementation of the care plan and 66% (n=25) had no evidence of outcome evaluation. Only 48% (n=41) of this at-risk population was nutritionally assessed. Of patients admitted with and without a pressure ulcer, there was no record of regular positioning in 70% (n=59) and 60% (n=51) respectively. CONCLUSION: Documentation on pressure ulcer care is not standardised and requires development. Conflict of interest: None.
    • An exploration of nursing documentation of pressure ulcer care in an acute setting in Ireland.

      O Brien, J A Jordan; Cowman, S; Beaumont Hospital, Dublin, Ireland. juliejordanobrien@beaumont.ie (2011-05)
      To explore the nature and quality of documented care planning for pressure ulcers in a large teaching hospital in the Republic of Ireland.
    • The expression and prognostic impact of CXC-chemokines in stage II and III colorectal cancer epithelial and stromal tissue

      Oladipo, O; Conlon, S; O'Grady, A; Purcell, C; Wilson, C; Maxwell, P J; Johnston, P G; Stevenson, M; Kay, E W; Wilson, R H; et al. (2011)
    • Expression profiles of endoplasmic reticulum stress-related molecules in demyelinating lesions and multiple sclerosis.

      Cunnea, Paula; Mháille, Aoife Ní; McQuaid, Stephen; Farrell, Michael; McMahon, Jill; FitzGerald, Una; NCBES, National University of Ireland, Galway, Ireland. (2011-07)
      Increasing evidence associates the endoplasmic reticulum (ER) stress signalling pathway as a potential treatment target in multiple sclerosis (MS).
    • Extra-corporeal membrane oxygenation in the management of 2009 influenza A (H1N1) refractory respiratory failure.

      Das, J P; Chew, N; Kitt, E; Murphy, C; O'Rourke, J; Power, M; McConkey, S J; Department of 1Infectious Disease, Beaumont Hospital, Beaumont, Dublin 9. (2012-02-01)
      Rapidly progressive acute respiratory failure attributed to 2009 H1N1 influenza A infection has been reported worldwide-3. Refractory hypoxaemia despite conventional mechanical ventilation and lung protective strategies has resulted in the use a combination of rescue therapies, such as conservative fluid management, prone positioning, inhaled nitric oxide, high frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO)4. ECMO allows for pulmonary or cardiopulmonary support as an adjunct to respiratory and cardiac failure, minimising ventilator-associated lung injury (VALI). This permits treatment of the underlying disease process, while concurrently allowing for recovery of the acute lung injury. This case documents a previously healthy twenty-two year old Asian male patient with confirmed pandemic (H 1N1) 2009 influenza A who was successfully managed with ECMO in the setting of severe refractory hypoxaemia and progressive hypercapnia.
    • Extra-corporeal membrane oxygenation in the management of 2009 influenza A (H1N1) refractory respiratory failure.

      Das, J P; Chew, N; Kitt, E; Murphy, C; O'Rourke, J; Power, M; McConkey, S J; Department of 1Infectious Disease, Beaumont Hospital, Beaumont, Dublin 9. (2011-03)
      Rapidly progressive acute respiratory failure attributed to 2009 H1N1 influenza A infection has been reported worldwide-3. Refractory hypoxaemia despite conventional mechanical ventilation and lung protective strategies has resulted in the use a combination of rescue therapies, such as conservative fluid management, prone positioning, inhaled nitric oxide, high frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO)4. ECMO allows for pulmonary or cardiopulmonary support as an adjunct to respiratory and cardiac failure, minimising ventilator-associated lung injury (VALI). This permits treatment of the underlying disease process, while concurrently allowing for recovery of the acute lung injury. This case documents a previously healthy twenty-two year old Asian male patient with confirmed pandemic (H 1N1) 2009 influenza A who was successfully managed with ECMO in the setting of severe refractory hypoxaemia and progressive hypercapnia.
    • Extubation versus tracheostomy in withdrawal of treatment-ethical, clinical, and legal perspectives.

      Chotirmall, Sanjay Haresh; Flynn, Maura G; Donegan, Ciaran F; Smith, David; O'Neill, Shane J; McElvaney, Noel Gerard; Department of Medicine - Respiratory Research Division, Royal College of Surgeons in Ireland, Education & Research Centre, Beaumont Hospital, Dublin 9, Republic of Ireland. schotirmall@rcsi.ie (2010-06)
      The provision of life-sustaining ventilation, such as tracheostomy to critically ill patients, is commonly performed. However, the utilization of tracheostomy or extubation after a withdrawal of treatment decision is debated. There is a dearth of practical information available to aid clinical decision making because withdrawal of treatment is a challenging scenario for all concerned. This is further complicated by medicolegal and ethical considerations. Care of the "hopelessly ill" patient should be based on daily evaluation and comfort making it impossible to fit into general algorithms. Although respect for autonomy is important in healthcare, it is limited for patients in an unconscious state. Beneficence remains the basis for withdrawing treatment in futile cases and underpins the "doctrine of double effect." This article presents a relevant clinical case of hypoxic brain injury where a question of withdrawal of treatment arose and examines the ethical, clinical, and medicolegal considerations inherent in such cases, including beneficence, nonmaleficence, and the "sanctity of life doctrine." In addition, the considerations of prognosis for recovery, patient autonomy, patient quality of life, and patient family involvement, which are central to decision making, are addressed. The varying legal frameworks that exist internationally regarding treatment withdrawal are also described. Good ethics needs sound facts, and despite the lack of legal foundation in several countries, withdrawal of treatment remains practiced, and the principles described within this article aim to aid clinician decision making during such complex and multifaceted end-of-life decisions.