• Acute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model.

      Connolly, Mary; Marrelli, Alessandra; Blades, Mark; McCormick, Jennifer; Maderna, Paola; Godson, Catherine; Mullan, Ronan; FitzGerald, Oliver; Bresnihan, Barry; Pitzalis, Costantino; et al. (Journal of immunology (Baltimore, Md. : 1950), 2010-06-01)
      Serum amyloid A (A-SAA), an acute-phase protein with cytokine-like properties, is expressed at sites of inflammation. This study investigated the effects of A-SAA on chemokine-regulated migration and angiogenesis using rheumatoid arthritis (RA) cells and whole-tissue explants in vitro, ex vivo, and in vivo. A-SAA levels were measured by real-time PCR and ELISA. IL-8 and MCP-1 expression was examined in RA synovial fibroblasts, human microvascular endothelial cells, and RA synovial explants by ELISA. Neutrophil transendothelial cell migration, cell adhesion, invasion, and migration were examined using transwell leukocyte/monocyte migration assays, invasion assays, and adhesion assays with or without anti-MCP-1/anti-IL-8. NF-kappaB was examined using a specific inhibitor and Western blotting. An RA synovial/SCID mouse chimera model was used to examine the effects of A-SAA on cell migration, proliferation, and angiogenesis in vivo. High expression of A-SAA was demonstrated in RA patients (p < 0.05). A-SAA induced chemokine expression in a time- and dose-dependent manner (p < 0.05). Blockade with anti-scavenger receptor class B member 1 and lipoxin A4 (A-SAA receptors) significantly reduced chemokine expression in RA synovial tissue explants (p < 0.05). A-SAA induced cell invasion, neutrophil-transendothelial cell migration, monocyte migration, and adhesion (all p < 0.05), effects that were blocked by anti-IL-8 or anti-MCP-1. A-SAA-induced chemokine expression was mediated through NF-kappaB in RA explants (p < 0.05). Finally, in the RA synovial/SCID mouse chimera model, we demonstrated for the first time in vivo that A-SAA directly induces monocyte migration from the murine circulation into RA synovial grafts, synovial cell proliferation, and angiogenesis (p < 0.05). A-SAA promotes cell migrational mechanisms and angiogenesis critical to RA pathogenesis.
    • An analytic observational study on complaints management in the general practice out of hours care setting: who complains, why, and what can we do about it?

      Barragry, Ruth A; Varadkar, Leo E; Hanlon, David K; Bailey, Ken F; O'Dowd, Tom C; O'Shea, Brendan J (BioMed Central, 2016)
      General Practice Co-Operatives provide most out of hours care in communities in Ireland. Limited data exists on patient complaints. This study reports on complaints at Kildare and West Wicklow Doctors on Call ('K Doc'), a GP Co-Operative in Ireland, examining the impact of a formal risk reduction strategy implemented (2010-2013). The aim of the study was to determine if it was possible to reduce the rate of written complaints per 1000 consultations through a formal approach encompassing evaluation of complaints, improved communication in relation to complaints, and more direct use of insights gained from complaints analysis in continuing professional development at the Co-Operative.
    • A changing trend in the management of patients with newly diagnosed Crohn's disease.

      Qasim, A; Ullah, N; Crotty, P; Swan, N; Breslin, N; Ryan, B; Torreggiani, W; Eguare, E; Neary, P; O'Connor, H; et al. (2012-02-01)
      BACKGROUND: Epidemiologic shift with rising incidence of Crohn's disease (CD) has been reported in recent studies. AIMS: To determine disease behaviour and therapeutic interventions undertaken in newly diagnosed patients with CD. METHODS: Patients diagnosed with CD between January 2006 and June 2008 were included. Disease type, location, degree of involvement and type of therapeutic interventions were recorded. RESULTS: A total of 78 patients were included. Colonic, ileo-colonic, terminal ileal and isolated small bowel disease were present in 37, 27, 9 and 5 patients, respectively. Disease phenotype was inflammatory, stenosing and fistulising in 42, 30 and 6 patients, respectively. Surgery was required in 22 patients, including right hemicolectomy (n = 8), subtotal colectomy (n = 4), segmental colonic resection (n = 2), segmental small bowel resection (n = 2), appendectomy (n = 2) and perianal surgery (n = 4). Fourteen patients underwent surgery at the time of diagnosis. Laparoscopic surgery was performed in 14 patients. CONCLUSIONS: A significant proportion of newly diagnosed patients with CD underwent surgical intervention on their first admission to hospital. This may signify a changing trend in the management approach.
    • Cinacalcet reduces plasma intact parathyroid hormone, serum phosphate and calcium levels in patients with secondary hyperparathyroidism irrespective of its severity.

      Frazão, J M; Messa, P; Mellotte, G J; Geiger, H; Hagen, E C; Quarles, L D; Kerr, P G; Baños, A; Dehmel, B; Urena, P; et al. (2011-09)
      To evaluate the relationship between the severity of secondary hyperparathyroidism (SHPT) - defined in terms of baseline plasma intact parathyroid hormone (iPTH) level - and the magnitude of response to cinacalcet.
    • Complex rectal polyps: other treatment modalities required when offering a transanal endoscopic microsurgery service.

      Joyce, Myles R; Eguare, Emmanuel; Kiernan, Fiona; Swan, Niall; Crotty, Paul; Neary, Paul; Keane, Frank B V; Division of Colorectal Surgery, The Adelaide & Meath Hospital, Tallaght, Dublin 24, Ireland. mylesjoyce@eircom.net (2011-09)
      Complex rectal polyps may present a clinical challenge. The study aim was to assess different treatment modalities required in the management of patients referred for transanal endoscopic microsurgery.
    • Confirmation of TNIP1 and IL23A as susceptibility loci for psoriatic arthritis.

      Bowes, John; Orozco, Gisela; Flynn, Edward; Ho, Pauline; Brier, Rasha; Marzo-Ortega, Helena; Coates, Laura; McManus, Ross; Ryan, Anthony W; Kane, David; et al. (Annals of the rheumatic diseases, 2011-09)
      To investigate a shared genetic aetiology for skin involvement in psoriasis and psoriatic arthritis (PsA) by genotyping single-nucleotide polymorphisms (SNPs), reported to be associated in genome-wide association studies of psoriasis, in patients with PsA.
    • Correlation between subcutaneous knee fat thickness and chondromalacia patellae on magnetic resonance imaging of the knee.

      Kok, Hong Kuan; Donnellan, John; Ryan, Davinia; Torreggiani, William C; Department of Radiology, Adelaide and Meath Hospital Incorporating the National Children's Hospital, Dublin, Ireland. terrykok@gmail.com (2013-08)
      Chondromalacia patellae is a common cause of anterior knee pain in young patients and can be detected noninvasively with magnetic resonance imaging (MRI). The purpose of our study was to evaluate the correlation between subcutaneous fat thickness around the knee joint on axial MRIs as a surrogate marker of obesity, with the presence or absence of chondromalacia patellae.
    • A cross-sectional study of the Birmingham Vasculitis Activity Score version 3 in systemic vasculitis.

      Suppiah, Ravi; Mukhtyar, Chetan; Flossmann, Oliver; Alberici, Federico; Baslund, Bo; Batra, Rajbir; Brown, Denise; Holle, Julia; Hruskova, Zdenka; Jayne, David R W; et al. (Rheumatology (Oxford, England), 2011-05)
      Assessment of disease activity in vasculitis can be achieved using the BVAS, a clinical checklist of relevant symptoms, signs and features of active disease. The aim of this study was to revalidate the BVAS version 3 (BVAS v. 3) in a cohort of patients with systemic vasculitis.
    • Dynamic electrocardiographic changes in patients with arrhythmogenic right ventricular cardiomyopathy.

      Quarta, Giovanni; Ward, Deirdre; Tomé Esteban, María T; Pantazis, Antonios; Elliott, Perry M; Volpe, Massimo; Autore, Camillo; McKenna, William J; The Heart Hospital, University College London Hospitals NHS Foundation Trust, 16-18 Westmoreland Street, London W1G 8PH, UK. william.mckenna@uclh.org (Heart (British Cardiac Society), 2010-04)
      Electrocardiographic (ECG) abnormalities of depolarisation and repolarisation contribute to the diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC). The development of diagnostic ECG features were investigated in a genotyped cohort with ARVC to provide more sensitive markers of early disease.
    • Electroejaculatory stimulation for male infertility secondary to spinal cord injury: the Irish experience in National Rehabilitation Hospital.

      McGuire, Ciara; Manecksha, Rustom P; Sheils, Pauline; McDermott, Thomas E D; Grainger, Ronald; Flynn, Robert; Department of Urology, Adelaide and Meath Hospital, Tallaght, Ireland. (2012-02-01)
      OBJECTIVES: To examine the success rate of electroejaculatory stimulation in patients with acquired spinal injuries in a single Irish institution. The use of electroejaculatory stimulation is of benefit in patients with spinal cord injury who wish to have children. METHODS: A retrospective review of the Hospital In-Patient Enquiry scheme database and the patients' medical notes was performed. Any patient who had undergone electroejaculatory stimulation in the past 14 years was included. The quality of semen obtained and the pregnancy rate were assessed in relation to several variables, including patient age and level of spinal injury. RESULTS: From 1994 to 2008, 31 patients (29 patients with acquired spinal injury and 2 patients with a congenital spinal abnormality) had undergone electroejaculatory stimulation as a method of providing semen for assisted conception. Of the 31 patients, 6 had requested cryopreservation of their semen for future use and were therefore excluded from the pregnancy rate analysis. Of the 25 patients who had used the semen, 9 (36%) were successful in achieving pregnancy that resulted in living offspring. The semen analysis results were available for 15 patients. Three patients (one each with contaminated semen, poor semen quality, and an abandoned procedure) required testicular biopsy to extract viable sperm and subsequently achieved pregnancy. Lower spinal lesions (below T10) were associated with lower rates of pregnancy after electroejaculatory stimulation. One patient developed autonomic dysreflexia during the procedure, which was therefore abandoned. CONCLUSIONS: Electroejaculatory stimulation is an effective method of obtaining semen for reproductive purposes and is an option for fertility preservation in patients with spinal cord injury-related anejaculation.
    • Epilepsy audit: do we document everything?

      Iqbal, M; Bilal, S; Sarwar, S; Murphy, R P; Department of Neurology, Adelaide and Meath Hospital, Tallaght, Dublin-24,, Ireland. mudassir213@hotmail.com (2012-02-01)
      BACKGROUND: An audit of the hospital notes and letters of patients with epilepsy sent to general practitioners was undertaken. AIMS: (a) To examine the frequency of important omissions in history taking and role of precipitants in seizure control, (b) to determine whether appropriate investigations had been performed and their results, (c) to assess whether letters sent to GPs contain all the appropriate information and advice, and to evaluate the waiting time for out-patient clinics and investigations. METHODS: This retrospective study was conducted in a teaching hospital setting. A computerised search of the clinical database of a consultant neurologist was performed on patients with epilepsy. The notes of the first 100 names selected randomly by the computer were analysed. The study period was during the years 1998-2005. Age range was from 17-72 years. The male:female ratio was 1:1. CONCLUSION: Major deficiencies in documentation were identified in this study.
    • Exclusion of homozygous PLCE1 (NPHS3) mutations in 69 families with idiopathic and hereditary FSGS.

      Gbadegesin, Rasheed; Bartkowiak, Bartlomiej; Lavin, Peter J; Mukerji, Nirvan; Wu, Guanghong; Bowling, Brandy; Eckel, Jason; Damodaran, Tirupapuliyur; Winn, Michelle P; Department of Pediatrics, Duke University Medical Center, Durham, NC, 27710, USA. rasheed.gbadegesin@duke.edu (Pediatric nephrology (Berlin, Germany), 2009-02)
      Focal and segmental glomerulosclerosis (FSGS) is the most common glomerular cause of end-stage kidney disease (ESKD). Although the etiology of FSGS has not been fully elucidated, recent results from the positional cloning of genes mutated in nephrotic syndromes are now beginning to provide insight into the pathogenesis of these diseases. Mutations in PLCE1/NPHS3 have recently been reported as a cause of nephrotic syndrome characterized by diffuse mesangial sclerosis (DMS) histology. One single family with a missense mutation had late onset of the disease that was characterized by FSGS. To further define the role of PLCE1 mutations in the etiology of FSGS, we performed mutational analysis in 69 families with FSGS. A total of 69 families with 231 affected individuals were examined. The median age of disease onset was 26 years (range 1-66 years). Onset of ESKD was at a median age of 35.5 years. Seven variants leading to non-synonymous changes were found, of which only two are new variants (exon 4 c.1682 G>A R561Q, exon 31 c.6518A>G K2173R). No known disease-causing mutations were identified in the families screened. PLCE1/NPHS3 mutations are not a cause of FSGS in this cohort. The absence of mutations in PLCE1/NPHS3 in this study indicates that there are additional genetic causes of FSGS and that hereditary FSGS is a heterogeneous disease. Kindreds appropriate for genome-wide screening are currently being subjected to analysis with the aim of identifying other genetic causes of FSGS.
    • Extended long term functional outcome of inflatable penile prosthesis in a single institution.

      Thomas, A Z; Carrol, R; Manecksha, R P; Thornhill, J A; Grainger, R; McDermott, T E D; AMNCH, Tallaght, Dublin 24 (Irish medical journal, 2011-02)
      We sought to evaluate the extended long term functional outcome of the AMS700 three piece inflatable prosthesis in men with erectile dysfunction in a single urological department and assess our revision rates. Patients that underwent first-time insertion or revision of an AMS700 3 piece inflatable penile prosthesis between 1984-2007 were included. Data was obtained from medical records and long term follow up of patients was conducted by telephone interview. The medical records of 38 patients were available for review. Of these 38 men, 56 prostheses were inserted. The mean follow up was 8.4 years (101 months). The revision rate at 50 months postoperatively was 7/38 (18%). The overall revision rate was 18/38 (47%). The mean time to revision in these 18 patients was 72 months (12-156 months) after initial insertion of AMS700 penile prosthesis. This study highlights that with longer follow u revision rates markedly increase after 72 months.
    • The Health Professions Admission Test (HPAT) score and leaving certificate results can independently predict academic performance in medical school: do we need both tests?

      Halpenny, D; Cadoo, K; Halpenny, M; Burke, J; Torreggiani, W C; Department of Radiology, AMNCH, Tallaght, Dublin 24. (2010-11)
      A recent study raised concerns regarding the ability of the health professions admission test (HPAT) Ireland to improve the selection process in Irish medical schools. We aimed to establish whether performance in a mock HPAT correlated with academic success in medicine. A modified HPAT examination and a questionnaire were administered to a group of doctors and medical students. There was a significant correlation between HPAT score and college results (r2: 0.314, P = 0.018, Spearman Rank) and between leaving cert score and college results (r2: 0.306, P = 0.049, Spearman Rank). There was no correlation between leaving cert points score and HPAT score. There was no difference in HPAT score across a number of other variables including gender, age and medical speciality. Our results suggest that both the HPAT Ireland and the leaving certificate examination could act as independent predictors of academic achievement in medicine.
    • High bone turnover in Irish professional jockeys.

      Waldron-Lynch, F; Murray, B F; Brady, J J; McKenna, M J; McGoldrick, A; Warrington, G; O'Loughlin, G; Barragry, J M; Adelaide and Meath Hospital, Dublin, Ireland. frank.waldron-lynch@yale.edu (2012-02-01)
      SUMMARY: Professional jockeys are routinely exposed to high impact trauma and sustain fractures frequently. We found that jockeys restrict their caloric intake in order to maintain regulation weights, and that bone turnover is high. There are significant health and safety implications for the racing industry. INTRODUCTION: Professional jockeys routinely sustain fractures from high impact falls. Jockeys maintain a low percentage body fat and a low body mass index (BMI) to achieve low weight targets in order to race. We evaluated dietary habits and bone metabolism in jockeys. METHODS: Bone mineral density (BMD) was measured in 27 male jockeys of the 144 jockeys licensed in Ireland. Fourteen (52%) had BMD T score below -1.0, of whom 12 consented to clinical review, nutritional survey, endocrine studies, and bone turnover markers (BTM). BTM were compared to age- and sex-matched controls (n = 16). RESULTS: BMI was 20.6 +/- 1.7 kg/m(2); previous fracture frequency was 3.2 +/- 2.0 per rider. All had normal endocrine axes. The jockeys' diet as determined by a 7-day dietary recall was deficient in energy, calcium, and vitamin D intake. Compared with the control group, the jockey group had evidence of increased bone turnover. CONCLUSIONS: A substantial proportion of the professional jockeys in Ireland have low-normal BMD, low BMI, and high bone turnover that may result from weight and dietary restrictions. These factors seem to have a deleterious effect on their bone health and predispose the jockeys to a high fracture risk that should be remediated.
    • Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial.

      Phelan, Niamh; O'Connor, Annalouise; Kyaw Tun, Tommy; Correia, Neuman; Boran, Gerard; Roche, Helen M; Gibney, James; Department of Endocrinology, Adelaide and Meath Hospital, Incorporating the, National Children's Hospital, Dublin, Ireland. (2012-02-01)
      BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by an adverse metabolic profile. Although dietary changes are advocated, optimal nutritional management remains uncertain. Polyunsaturated fatty acids (PUFAs), particularly long-chain (LC) n-3 (omega-3) PUFAs, improve metabolic health, but their therapeutic potential in PCOS is unknown. OBJECTIVES: We aimed to determine the associations between plasma PUFAs and metabolic and hormonal aspects of PCOS to investigate the efficacy of LC n-3 PUFA supplementation and to support the findings with mechanistic cellular studies. DESIGN: We selected a cross-sectional PCOS cohort (n = 104) and conducted a principal component analysis on plasma fatty acid profiles. Effects of LC n-3 PUFA supplementation on fasting and postprandial metabolic and hormonal markers were determined in PCOS subjects (n = 22) by a randomized, crossover, placebo-controlled intervention. Direct effects of n-6 (omega-6) compared with n-3 PUFAs on steroidogenesis were investigated in primary bovine theca cells. RESULTS: Cross-sectional data showed that a greater plasma n-6 PUFA concentration and n-6:n-3 PUFA ratio were associated with higher circulating androgens and that plasma LC n-3 PUFA status was associated with a less atherogenic lipid profile. LC n-3 PUFA supplementation reduced plasma bioavailable testosterone concentrations (P < 0.05), with the greatest reductions in subjects who exhibited greater reductions in plasma n-6:n-3 PUFA ratios. The treatment of bovine theca cells with n-6 rather than with n-3 PUFAs up-regulated androstenedione secretion (P < 0.05). CONCLUSIONS: Cross-sectional data suggest that PUFAs modulated hormonal and lipid profiles and that supplementation with LC n-3 PUFAs improves androgenic profiles in PCOS. In bovine theca cells, arachidonic acid modulated androstenedione secretion, which suggests an indirect effect of n-3 PUFAs through the displacement of or increased competition with n-6 PUFAs. This trial was registered at clinicaltrials.gov as NCT01189669.
    • Identification of the optimal donor quality scoring system and measure of early renal function in kidney transplantation.

      Moore, Jason; Ramakrishna, Satish; Tan, Kay; Cockwell, Paul; Eardley, Kevin; Little, Mark A; Rylance, Paul; Shivakumar, Kunigal; Suresh, Vijayan; Tomlinson, Kerry; et al. (Transplantation, 2009-02-27)
      The early identification of kidney allografts at risk of later dysfunction has implications for clinical practice. Donor quality scoring systems (preoperative) and measures of early allograft function (first week postoperative) have previously shown practical utility. This study aimed to determine the optimal parameter(s) (preoperative and postoperative) with greatest predictive power for the development of subsequent allograft dysfunction.
    • Imaging spectrum of sudden athlete cardiac death.

      Arrigan, M T; Killeen, R P; Dodd, J D; Torreggiani, W C; Department of Radiology, Adelaide and Meath Hospital incorporating the National, Children's Hospital, Dublin, Ireland. martinarrigan@gmail.com (2012-02-01)
      Sudden athlete death (SAD) is a widely publicized and increasingly reported phenomenon. For many, the athlete population epitomize human physical endeavour and achievement and their unexpected death comes with a significant emotional impact on the public. Sudden deaths within this group are often without prior warning. Preceding symptoms of exertional syncope and chest pain do, however, occur and warrant investigation. Similarly, a positive family history of sudden death in a young person or a known family history of a condition associated with SAD necessitates further tests. Screening programmes aimed at detecting those at risk individuals also exist with the aim of reducing fatalities. In this paper we review the topic of SAD and discuss the epidemiology, aetiology, and clinical presentations. We then proceed to discuss each underlying cause, in turn discussing the pathophysiology of each condition. This is followed by a discussion of useful imaging methods with an emphasis on cardiac magnetic resonance and cardiac computed tomography and how these address the various issues raised by the pathophysiology of each entity. We conclude by proposing imaging algorithms for the investigation of patients considered at risk for these conditions and discuss the various issues raised in screening.
    • Immune profile and Epstein-Barr virus infection in acute interstitial nephritis: an immunohistochemical study in 78 patients.

      Mansur, Abdurrezagh; Little, Mark A; Oh, Weng Chin; Jacques, Steven; Nightingale, Peter; Howie, Alexander J; Savage, Caroline O S; Renal Immunobiology, University of Birmingham, College of Medical and Dental Sciences, London, UK. (Nephron. Clinical practice, 2011)
      Acute interstitial nephritis (AIN) is a common cause of acute kidney injury and is characterised by a dense interstitial cellular infiltrate, which has not been well defined. Previous studies have demonstrated a correlation between Epstein-Barr virus (EBV) infection and AIN. The purpose of our study was to define the nature of the interstitial immune infiltrate and to investigate the possibility of renal infection with EBV.
    • Is simple nephrectomy truly simple? Comparison with the radical alternative.

      Connolly, S S; O'Brien, M Frank; Kunni, I M; Phelan, E; Conroy, R; Thornhill, J A; Grainger, R; Department of Urology, Trinity College Dublin, Adelaide and Meath incorporating National Children's Hospital, Tallaght, Dublin 24, Ireland. steconnolly@rcsi.ie (2011-03)
      The Oxford English dictionary defines the term "simple" as "easily done" and "uncomplicated". We tested the validity of this terminology in relation to open nephrectomy surgery.