• Obesity and disability in the symptomatic Irish knee osteoarthritis population.

      Ambrose, N L; Keogan, F; O'Callaghan, J P; O'Connell, P G; Beaumont Hospital, Dublin, Ireland. nicolaambrose@yahoo.ie (2010-06)
      Osteoarthritis (OA) of the knee is a common disorder with significant social and financial implications. Obesity is the strongest modifiable risk factor of knee OA. There is little data on obesity in Irish knee OA populations and its relationship to other measures of disease severity.
    • Oesophageal achalasia: an argument for primary surgical management.

      Leonard, D S; Broe, P; Department of Surgery Beaumont Hospital, Dublin, Ireland. leonarddavid@eircom.net (2009-04)
      Achalasia is a primary oesophageal motility disorder resulting from damage to the ganglion cells of the myenteric plexus. Impaired relaxation of the lower oesophageal sphincter and aperistalsis causes its cardinal symptoms of dysphagia, chest pain and reflux-type symptoms. Management is somewhat controversial, with options including systemic and local pharmacotherapy, dilatation and oesophagomyotomy. We review the presentation, investigation and management of oesophageal achalasia and make an argument for primary surgical management.
    • Olfactory receptor signaling is regulated by the post-synaptic density 95, Drosophila discs large, zona-occludens 1 (PDZ) scaffold multi-PDZ domain protein 1.

      Dooley, Ruth; Baumgart, Sabrina; Rasche, Sebastian; Hatt, Hanns; Neuhaus, Eva M; Molecular Medicine Lab RCSI, Beaumont Hospital, Dublin, Republic of Ireland. (2009-12)
      The unique ability of mammals to detect and discriminate between thousands of different odorant molecules is governed by the diverse array of olfactory receptors expressed by olfactory sensory neurons in the nasal epithelium. Olfactory receptors consist of seven transmembrane domain G protein-coupled receptors and comprise the largest gene superfamily in the mammalian genome. We found that approximately 30% of olfactory receptors possess a classical post-synaptic density 95, Drosophila discs large, zona-occludens 1 (PDZ) domain binding motif in their C-termini. PDZ domains have been established as sites for protein-protein interaction and play a central role in organizing diverse cell signaling assemblies. In the present study, we show that multi-PDZ domain protein 1 (MUPP1) is expressed in the apical compartment of olfactory sensory neurons. Furthermore, on heterologous co-expression with olfactory sensory neurons, MUPP1 was shown to translocate to the plasma membrane. We found direct interaction of PDZ domains 1 + 2 of MUPP1 with the C-terminus of olfactory receptors in vitro. Moreover, the odorant-elicited calcium response of OR2AG1 showed a prolonged decay in MUPP1 small interfering RNA-treated cells. We have therefore elucidated the first building blocks of the putative 'olfactosome', brought together by the scaffolding protein MUPP1, a possible central nucleator of the olfactory response.
    • On the development of markers for pathological TDP-43 in amyotrophic lateral sclerosis with and without dementia.

      Geser, F; Prvulovic, D; O'Dwyer, L; Hardiman, O; Bede, P; Bokde, A L W; Trojanowski, J Q; Hampel, H; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe-University, Frankfurt am Main, Germany. felix.geser@alumni.i-med.ac.at (2011-12)
      Pathological 43-kDa transactive response sequence DNA-binding protein (TDP-43) has been recognized as the major disease protein in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with ubiquitin positive, tau and α-synuclein negative inclusions (FTLD-U) and the transitional forms between these multisystem conditions. In order to develop TDP-43 into a successful ALS biomarker, the natural history of TDP-43 pathology needs to be characterized and the underlying pathophysiology established. Here we propose a spatial and temporal "two-axes" model of central nervous system vulnerability for TDP-43 linked degeneration and review recent studies on potential biomarkers related to pathological TDP-43 in the cerebrospinal fluid (CSF), blood, and skeletal muscle. The model includes the following two arms: Firstly, a "motor neuron disease" or "spinal cord/brainstem to motor cortex" axis (with degeneration possibly ascending from the lower motor neurons to the upper motor neurons); and secondly, a "dementia" or "corticoid/allocortex to neocortex" axis (with a probable spread of TDP-43 linked degeneration from the mediotemporal lobe to wider mesocortical and neocortical brain areas). At the cellular level, there is a gradual disappearance of normal TDP-43 in the nucleus in combination with the formation of pathological aggregates in the cell body and cellular processes, which can also be used to identify the stage of the disease process. Moreover, TDP-43 lesions in subpial/subependymal or perivascular localizations have been noted, and this might account for increased CSF and blood TDP-43 levels through mechanisms that remain to be elucidated.
    • ON003 From motivated and compliant to empowered: Do we need an IBD nurse led self management programme?

      Forry, M.; Godwin, N.; Kelly, O.; Harewood, G.; Murray, F.; Patchett, S. (Elsevier, 2012-02)
    • Operating table manoeuvring during otological procedures.

      Barghouthi, T; Glynn, F; Walshe, P; Viani, L; Department of Otolaryngology and Cochlear Implantation, Beaumont Hospital, Dublin 9, Ireland. E-mail: talebbarghouthi@gmail.com. (2011-06)
    • Operative innovations for colorectal cancer.

      Cahill, R A; Lindsey, I; Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland., cahillra@gmail.com (2012-02-01)
    • Operative techniques for cervical radiculopathy and myelopathy.

      Moran, C; Bolger, C; National Centre for Neurosurgery, Beaumont Hospital, Dublin, Ireland. (2012-02-01)
      The surgical treatment of cervical spondylosis and resulting cervical radiculopathy or myelopathy has evolved over the past century. Surgical options for dorsal decompression of the cervical spine includes the traditional laminectomy and laminoplasty, first described in Asia in the 1970's. More recently the dorsal approch has been explored in terms of minimally invasive options including foraminotomies for nerve root descompression. Ventral decompression and fusion techniques are also described in the article, including traditional anterior cervical discectomy and fusion, strut grafting and cervical disc arthroplasty. Overall, the outcome from surgery is determined by choosing the correct surgery for the correct patient and pathology and this is what we hope to explain in this brief review.
    • Ophthalmological screening of a paediatric cochlear implant population: a retrospective analysis and 12-year follow-up.

      Falzon, K; Guerin, M; Fulcher, T; Viani, L; Department of Ophthalmology, Beaumont University Hospital, Dublin, Ireland. kev.falzon@gmail.com (2010-06)
      To determine the nature and prevalence of ophthalmological findings for a cohort of children in a paediatric cochlear implant program and to assist the clinician in devising an investigative plan for this population.
    • Optimising glucocorticoid replacement therapy in severely adrenocorticotropin (ACTH) deficient hypopituitary male patients.

      Behan, Lucy-Ann; Rogers, Bairbre; Hannon, Mark J; O'Kelly, Patrick; Tormey, William; Smith, Diarmuid; Thompson, Christopher J; Agha, Amar; Division of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin, Ireland Department of Statistics, Beaumont Hospital, Dublin, Ireland Department of Chemical Pathology, Beaumont Hospital, Dublin, Ireland. (2011-04-18)
      Context:  The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15mg to 30mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. Objective:  Primarily to define the hydrocortisone regimen which results in a 24hour cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). Design:  10 male hypopituitary patients with severe ACTH deficiency (basal cortisol <100nM and peak response to stimulation <400nM) were enrolled in a prospective, randomised, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24hour serum cortisol sampling and QoL assessment with the Short Form 36 and the Nottingham Health Profile questionnaires. Free cortisol was calculated using Coolen's equation. All results were compared to those of healthy, matched controls. Results:  CBG was significantly lower across all dose regimens compared to controls (p<0.05). The lower dose regimen C(10mg mane/5mg tarde) produced a 24hour free cortisol profile which most closely resembled that of controls. Both regimen A(20mg mane/10mg tarde) and B(10mg mane/10mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (p<0.001). Conclusions:  The lower dose of HC(10mg/5mg) produces a more physiological cortisol profile, without compromising quality of life, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.
    • Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin-deficient hypopituitary male patients.

      Behan, Lucy-Ann; Rogers, Bairbre; Hannon, Mark J; O'Kelly, Patrick; Tormey, William; Smith, Diarmuid; Thompson, Christopher J; Agha, Amar; Division of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin,, Ireland. (2012-02-01)
      BACKGROUND: The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15-30 mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. OBJECTIVE: Primarily to define the hydrocortisone regimen which results in a 24 h cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). DESIGN: Ten male hypopituitary patients with severe ACTH deficiency (basal cortisol <100 nm and peak response to stimulation <400 nm) were enrolled in a prospective, randomized, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24 h serum cortisol sampling and QoL assessment with the Short Form 36 (SF36) and the Nottingham Health Profile (NHP) questionnaires. Free cortisol was calculated using Coolen's equation. All results were compared to those of healthy, matched controls. RESULTS: Corticosteroid binding globulin (CBG) was significantly lower across all dose regimens compared to controls (P < 0.05). The lower dose regimen C (10 mg mane/5 mg tarde) produced a 24 h free cortisol profile (FCP) which most closely resembled that of controls. Both regimen A(20 mg mane/10 mg tarde) and B(10 mg mane/10 mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (P < 0.001). CONCLUSIONS: The lower dose of hydrocortisone (10 mg/5 mg) produces a more physiological cortisol profile, without compromising QoL, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.
    • Optional inferior vena caval filters: where are we now?

      Keeling, A N; Kinney, T B; Lee, M J; Department of Academic Radiology, Beaumont Hospital, Beaumont Road, Dublin 9, Ireland. (2008-08)
      With the advent of newer optional/retrievable inferior vena caval filters, there has been a rise in the number of filters inserted globally. This review article examines the currently available approved optional filter models, outlines the clinical indications for filter insertion and examines the expanding indications. Additionally, the available evidence behind the use of optional filters is reviewed, the issue of anticoagulation is discussed and possible future filter developments are considered.
    • Organ donation following the circulatory determination of death

      O’Rourke, J; Zimmermann, JA; Shields, W; McLaughlin, D; Cunningham, P; Magee, C; Hickey, DP (Irish Medical Journal, 2014-01)
      Organ Donation following the Circulatory determination of Death was introduced in Beaumont Hospital during 2011. The Intensive Care Society of Ireland formally endorsed a national DCD clinical practice guideline in 2012. This retrospective audit covers a 2-year period during which eleven patients were considered suitable for DCD and where consent was obtained. Nine patients died within the ninety-minute period following the withdrawal of life sustaining therapies and subsequently donated organs (82%). Eighteen kidneys were recovered and seventeen patients received renal transplants - one patient received a nephron-dosing dual renal transplant. Lungs were recovered on two occasions and one patient received a lung transplant. Heart valves were recovered on one occasion. To date sixteen of seventeen recipient patients have functioning renal transplants (94%). In conclusion, this model of deceased donation has proven acceptable to families, nursing and medical staff and the outcomes reported are consistent with international best practice.
    • Osteoprotegerin and biomarkers of vascular inflammation in type 2 diabetes.

      O'Sullivan, Eoin P; Ashley, David T; Davenport, Colin; Devlin, Niamh; Crowley, Rachel; Agha, Amar; Thompson, Christopher J; O'Gorman, Donal; Smith, Diarmuid; Department of Diabetes, Royal College of Surgeons in Ireland Medical School, Beaumont Hospital, Dublin, Ireland. (2010-09)
      Osteoprotegerin (OPG), receptor activator for nuclear factor kappa beta ligand (RANKL) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) are newly discovered members of the tumour necrosis factor-alpha receptor superfamily. While their role in bone metabolism is well described, their function within the vasculature is poorly understood. OPG inhibits vascular calcification in vitro and high serum levels have been demonstrated in type 2 diabetes, but serum RANKL and TRAIL and their potential correlation with well-established biomarkers of subclinical vascular inflammation such as high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) have not been described.
    • Osteoprotegerin is higher in peripheral arterial disease regardless of glycaemic status.

      O'Sullivan, Eoin P; Ashley, David T; Davenport, Colin; Kelly, James; Devlin, Niamh; Crowley, Rachel; Leahy, Austin L; Kelly, Cathal J; Agha, Amar; Thompson, Christopher J; et al. (2010-12)
      Peripheral arterial disease (PAD) and type 2 diabetes mellitus (DM) are both associated with excessive vascular calcification and elevated levels of inflammatory markers IL-6 and hsCRP. The recently identified Osteoprotegerin(OPG)/RANKL/TRAIL pathway has been implicated in vascular calcification, but data on levels in PAD and effect of co-existent DM are lacking.
    • Outcome and complications of bronchial artery embolisation for life-threatening haemoptysis.

      Slattery, M M; Keeling, A N; Lee, M J; Department of Radiology, Beaumont Hospital, Beaumont Road, Dublin 9, Ireland. mlslattery@hotmail.com (2009-06)
      Bronchial artery embolisation (BAE) has been established as an effective technique in the emergency treatment of life-threatening haemoptysis. However, few data concerning outcome are available.
    • Outcomes of patients presenting to a dedicated rapid access lung cancer clinic.

      Dunican, E; Uzbeck, M; Clince, J; Toner, S; Royston, D; Logan, M P; Breathnach, O; Young, V; Linnane, S I; Morgan, R K; et al. (2012-02-01)
      We examined the outcomes of the first 500 patients referred to a dedicated Rapid Access Lung Cancer Clinic. A total of 206 patients (41.2%) were diagnosed with a thoracic malignancy; 179 had primary lung cancer and 27 had secondary or other thoracic cancers. Pulmonary nodules requiring ongoing surveillance were found in a further 79 patients (15.8%). Of those patients found to have primary lung cancer, 24 (13.4%) had Small Cell and 145 (81%) had Non Small Cell Lung Cancer. In patients with Non small cell tumours, 26 (21.1%) were stage 1, 14 (11.4%) stage II, 37 (30.1%) stage III and 46 (37.4%) stage IV at diagnosis. For the 129 patients (72%) in whom the thoracic MDT recommended active treatment, primary therapy was surgical resection in 44 (24.6%), combined chemoradiation in 31 patients (17.3%), chemotherapy alone in 39 (21.8%) and radiation in 15 (8.4%).
    • Ovarian inflammatory myofibroblastic tumour fistulating on to the anterior abdominal wall.

      Khan, G; Treacy, A; Garvey, J P; Png, B; Walshe, J; Leader, M; Byrne, P; Departments of Gynaecology, Beaumont Hospital, Beaumont, Dublin, Ireland. ghazala.sheraz.khan@gmail.com (2010-01)
    • Overcoming resistance and restoring sensitivity to HER2-targeted therapies in breast cancer.

      Mohd Sharial, M S N; Crown, J; Hennessy, B T; Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland. (2012-12)
      Approximately 15%-23% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2), which leads to the activation of signaling pathways that stimulate cell proliferation and survival. HER2-targeted therapy has substantially improved outcomes in patients with HER2-positive breast cancer. However, both de novo and acquired resistance are observed.
    • Paediatric cyclical Cushing's disease due to corticotroph cell hyperplasia.

      Noctor, E; Gupta, S; Brown, T; Farrell, M; Javadpour, M; Costigan, C; Agha, A (BioMed Central, 2015-06)
      Cushing's disease is very rare in the paediatric population. Although uncommon, corticotroph hyperplasia causing Cushing's syndrome has been described in the adult population, but appears to be extremely rare in children. Likewise, cyclical cortisol hypersecretion, while accounting for 15 % of adult cases of Cushing's disease, has only rarely been described in the paediatric population. Here, we describe a very rare case of a 13-year old boy with cyclical cortisol hypersecretion secondary to corticotroph cell hyperplasia.