• T cells in multiple sclerosis and experimental autoimmune encephalomyelitis.

      Fletcher, J M; Lalor, S J; Sweeney, C M; Tubridy, N; Mills, K H G; Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity , College, St Vincent's University Hospital, Dublin, Ireland. (2012-02-01)
      Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS), which involves autoimmune responses to myelin antigens. Studies in experimental autoimmune encephalomyelitis (EAE), an animal model for MS, have provided convincing evidence that T cells specific for self-antigens mediate pathology in these diseases. Until recently, T helper type 1 (Th1) cells were thought to be the main effector T cells responsible for the autoimmune inflammation. However more recent studies have highlighted an important pathogenic role for CD4(+) T cells that secrete interleukin (IL)-17, termed Th17, but also IL-17-secreting gammadelta T cells in EAE as well as other autoimmune and chronic inflammatory conditions. This has prompted intensive study of the induction, function and regulation of IL-17-producing T cells in MS and EAE. In this paper, we review the contribution of Th1, Th17, gammadelta, CD8(+) and regulatory T cells as well as the possible development of new therapeutic approaches for MS based on manipulating these T cell subtypes.
    • A Temporal Comparative Study of Women’s Rugby Injuries Presenting to an Emergency Department

      Gilmartin, S.; Ryan, J. (Irish Medical Journal, 2019-10)
      We aimed to examine the change in injury patterns, diagnostics and treatments provided to female rugby players in an emergency department between two separate seasons ten years apart.
    • Temporal discrimination threshold: VBM evidence for an endophenotype in adult onset primary torsion dystonia.

      Bradley, D; Whelan, R; Walsh, R; Reilly, R B; Hutchinson, S; Molloy, F; Hutchinson, M; Department of Neurology, St Vincent's University Hospital, Dublin, Ireland., david.bradley@ucd.ie (2012-02-01)
      Familial adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance. Most adult-onset primary torsion dystonia patients are sporadic cases. Disordered sensory processing is found in adult-onset primary torsion dystonia patients; if also present in their unaffected relatives this abnormality may indicate non-manifesting gene carriage. Temporal discrimination thresholds (TDTs) are abnormal in adult-onset primary torsion dystonia, but their utility as a possible endophenotype has not been examined. We examined 35 adult-onset primary torsion dystonia patients (17 familial, 18 sporadic), 42 unaffected first-degree relatives of both familial and sporadic adult-onset primary torsion dystonia patients, 32 unaffected second-degree relatives of familial adult-onset primary torsion dystonia (AOPTD) patients and 43 control subjects. TDT was measured using visual and tactile stimuli. In 33 unaffected relatives, voxel-based morphometry was used to compare putaminal volumes between relatives with abnormal and normal TDTs. The mean TDT in 26 control subjects under 50 years of age was 22.85 ms (SD 8.00; 95% CI: 19.62-26.09 ms). The mean TDT in 17 control subjects over 50 years was 30.87 ms (SD 5.48; 95% CI: 28.05-33.69 ms). The upper limit of normal, defined as control mean + 2.5 SD, was 42.86 ms in the under 50 years group and 44.58 ms in the over 50 years group. Thirty out of thirty-five (86%) AOPTD patients had abnormal TDTs with similar frequencies of abnormalities in sporadic and familial patients. Twenty-two out of forty-two (52%) unaffected first-degree relatives had abnormal TDTs with similar frequencies in relatives of sporadic and familial AOPTD patients. Abnormal TDTs were found in 16/32 (50%) of second-degree relatives. Voxel-based morphometry analysis comparing 13 unaffected relatives with abnormal TDTs and 20 with normal TDTs demonstrated a bilateral increase in putaminal grey matter in unaffected relatives with abnormal TDTs. The prevalence of abnormal TDTs in sporadic and familial AOPTD patients and their first-degree relatives follows the rules for a useful endophenotype. A structural correlate of abnormal TDTs in unaffected first-degree relatives was demonstrated using voxel-based morphometry. Voxel-based morphometry findings indicate that putaminal enlargement in AOPTD is a primary phenomenon. TDTs may be an effective tool in AOPTD research with particular relevance to genetic studies of the disorder.
    • Temporal discrimination thresholds in adult-onset primary torsion dystonia: an analysis by task type and by dystonia phenotype.

      Bradley, D; Whelan, R; Kimmich, O; O'Riordan, S; Mulrooney, N; Brady, P; Walsh, R; Reilly, R B; Hutchinson, S; Molloy, F; et al. (2012-01)
      Adult-onset primary torsion dystonia (AOPTD) is an autosomal dominant disorder with markedly reduced penetrance. Sensory abnormalities are present in AOPTD and also in unaffected relatives, possibly indicating non-manifesting gene carriage (acting as an endophenotype). The temporal discrimination threshold (TDT) is the shortest time interval at which two stimuli are detected to be asynchronous. We aimed to compare the sensitivity and specificity of three different TDT tasks (visual, tactile and mixed/visual-tactile). We also aimed to examine the sensitivity of TDTs in different AOPTD phenotypes. To examine tasks, we tested TDT in 41 patients and 51 controls using visual (2 lights), tactile (non-painful electrical stimulation) and mixed (1 light, 1 electrical) stimuli. To investigate phenotypes, we examined 71 AOPTD patients (37 cervical dystonia, 14 writer's cramp, 9 blepharospasm, 11 spasmodic dysphonia) and 8 musician's dystonia patients. The upper limit of normal was defined as control mean +2.5 SD. In dystonia patients, the visual task detected abnormalities in 35/41 (85%), the tactile task in 35/41 (85%) and the mixed task in 26/41 (63%); the mixed task was less sensitive than the other two (p = 0.04). Specificity was 100% for the visual and tactile tasks. Abnormal TDTs were found in 36 of 37 (97.3%) cervical dystonia, 12 of 14 (85.7%) writer's cramp, 8 of 9 (88.8%) blepharospasm, 10 of 11 (90.1%) spasmodic dysphonia patients and 5 of 8 (62.5%) musicians. The visual and tactile tasks were found to be more sensitive than the mixed task. Temporal discrimination threshold results were comparable across common adult-onset primary torsion dystonia phenotypes, with lower sensitivity in the musicians.
    • Tender erythematous papules on the elbows, buttocks and knees.

      Ryan, A J A; Hayes, B D; Sheahan, K; Collins, P; Department of Dermatology, St Vincent's University Hospital, Dublin, Ireland., ajryan99@gmail.com (2012-02-01)
    • Time course and recovery of arterial blood gases during exacerbations in adults with Cystic Fibrosis.

      Waterhouse, D F; McLaughlin, A M; Gallagher, C G; Department of Respiratory Medicine, St. Vincent's University Hospital, Ireland. (2012-02-01)
      INTRODUCTION: Hypoxia and hypercapnia are closely linked to morbidity and mortality in patients with Cystic Fibrosis (CF). The aims of this study were to describe the changes in blood gases during and following an acute pulmonary exacerbation in adults with CF. METHODS: We performed a prospective observational study of patients with CF admitted for management of an acute exacerbation. Blood gas and spirometric analysis was performed on admission, throughout the treatment period, and 31 days after discharge (day 45). RESULTS: At presentation, eight of nineteen patients had evidence of either hypoxia (PaO(2)<8 kPa) and/or hypercapnia (PaCO(2)>6.6 kPa). Blood gas parameters stabilized following two weeks of intravenous antibiotic therapy, with little difference evident in between treatment completion and subsequent review following discharge. Hypercapnia reversed in three patients, with persistent hypercapnia evident in two patients. CONCLUSION: In our study group, hypoxemia and hypercapnia were frequently observed at presentation of the acute exacerbation. Blood gases stabilized following two weeks of intravenous antibiotic therapy, with arterial PCO(2) one month following hospital discharge generally similar to that at time of discharge.
    • Time for the endocrinologists to expand their awareness of and contribution to the diagnosis and management of encephalopathy associated with autoimmune thyroid disease.

      Tamagno, Gianluca; Gaoatswe, Gadintshware; Department of Endocrinology & Diabetes Mellitus, St Vincent's University Hospital, University College Dublin, Ireland. gianlucatamagno@tiscali.it (2011-01)
      Encephalopathy associated with autoimmune thyroid disease is a rare condition presenting in the setting of autoimmune thyroid disease and characterized by unspecific neurological and/or psychiatric symptoms. Bearing in mind the currently prevailing lack of consensus on the most appropriate nomenclature and diagnostic criteria for this condition and the implications that this lack undeniably has on clinical practice, it is obvious that an international and multidisciplinary agreement among clinicians should arrive at the most appropriate definition and terminology of encephalopathy occurring in patients with autoimmune thyroid disease. Concomitantly, efforts must be made to uncover the pathogenetic link between thyroid autoimmunity and the occurrence of encephalopathy.
    • Time for the endocrinologists to expand their awareness of and contribution to the diagnosis and management of encephalopathy associated with autoimmune thyroid disease.

      Tamagno, Gianluca; Gaoatswe, Gadintshware; Department of Endocrinology & Diabetes Mellitus, St Vincent's University, Hospital, University College Dublin, Ireland. gianlucatamagno@tiscali.it (2012-02-01)
      Encephalopathy associated with autoimmune thyroid disease is a rare condition presenting in the setting of autoimmune thyroid disease and characterized by unspecific neurological and/or psychiatric symptoms. Bearing in mind the currently prevailing lack of consensus on the most appropriate nomenclature and diagnostic criteria for this condition and the implications that this lack undeniably has on clinical practice, it is obvious that an international and multidisciplinary agreement among clinicians should arrive at the most appropriate definition and terminology of encephalopathy occurring in patients with autoimmune thyroid disease. Concomitantly, efforts must be made to uncover the pathogenetic link between thyroid autoimmunity and the occurrence of encephalopathy.
    • TIRADS Management Guidelines in the Investigation of Thyroid Nodules; Illustrating the Concerns, Costs, and Performance.

      Cawood, Tom James; Mackay, Georgia Rose; Hunt, Penny Jane; O'Shea, Donal; Skehan, Stephen; Ma, Yi (2020-03-10)
      Context: Ultrasound (US) risk-stratification systems for investigation of thyroid nodules may not be as useful as anticipated. Objective: We aimed to assess the performance and costs of the American College of Radiology Thyroid Image Reporting And Data System (ACR-TIRADS). Design settings and participants: We examined the data set upon which ACR-TIRADS was developed, and applied TR1 or TR2 as a rule-out test, TR5 as a rule-in test, or applied ACR-TIRADS across all nodule categories. We assessed a hypothetical clinical comparator where 1 in 10 nodules are randomly selected for fine needle aspiration (FNA), assuming a pretest probability of clinically important thyroid cancer of 5%. Results: The gender bias (92% female) and cancer prevalence (10%) of the data set suggests it may not accurately reflect the intended test population. Applying ACR-TIRADS across all nodule categories did not perform well, with sensitivity and specificity between 60% and 80% and overall accuracy worse than random selection (65% vs 85%). Test performance in the TR3 and TR4 categories had an accuracy of less than 60%. Using TR5 as a rule-in test was similar to random selection (specificity 89% vs 90%). Using TR1 and TR2 as a rule-out test had excellent sensitivity (97%), but for every additional person that ACR-TIRADS correctly reassures, this requires >100 ultrasound scans, resulting in 6 unnecessary operations and significant financial cost. Conclusions: Perhaps surprisingly, the performance ACR-TIRADS may often be no better than random selection. The management guidelines may be difficult to justify from a cost/benefit perspective. A prospective validation study that determines the true performance of TIRADS in the real-world is needed.
    • To Hydrate or Not at the End of Life

      Lunny, B (Irish Medical Journal, 2012-06)
    • Toll-like receptor 2 (TLR2) induces migration and invasive mechanisms in rheumatoid arthritis.

      McGarry, Trudy; Veale, Douglas J; Gao, Wei; Orr, Carl; Fearon, Ursula; Connolly, Mary (Springer, 2015)
      This study investigates the role of Toll-like receptor 2 (TLR2) in the regulation of migratory and invasive mechanisms in rheumatoid arthritis (RA).
    • Torsion of monofilament and polyfilament sutures under tension decreases suture strength and increases risk of suture fracture.

      Hennessey, D B; Carey, E; Simms, C K; Hanly, A; Winter, D C; Department of General and Colorectal Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. derek.hennessey@gmail.com (2012-08)
      A continuous running suture is the preferential method for abdominal closure. In this technique the suture is secured with an initial knot and successive tissue bites are taken. At each tissue bite, the needle is rotated through the tissue; in doing so, the suture can twist around the knot which acts as an anchor.
    • Tracheomalacia in adults with cystic fibrosis: determination of prevalence and severity with dynamic cine CT.

      McDermott, Shaunagh; Barry, Sinead C; Judge, Eoin E; Collins, Susan; de Jong, Pim A; Tiddens, Harm A W M; McKone, Edward F; Gallagher, Charles C; Dodd, Jonathan D; Department of Radiology, St Vincent's University Hospital, Elm Park, Dublin 4,, Ireland. (2012-02-01)
      PURPOSE: To determine the prevalence and severity of tracheomalacia in adults with cystic fibrosis (CF) by using dynamic cine multidetector computed tomography (CT) and to correlate these findings with pulmonary function test (PFT) results and the severity of parenchymal lung disease. MATERIALS AND METHODS: In this institutional review board-approved HIPAA-compliant study, 40 patients with CF (22 men, 18 women; mean age, 28 years +/- 8 [standard deviation]; age range, 18-54 years) prospectively underwent PFTs, standard thin-section CT, and two dynamic cine multidetector CT acquisitions. Ten control subjects underwent dynamic cine multidetector CT. After standard thin-section CT was completed, dynamic cine multidetector CT was performed during a forced expiratory maneuver and during coughing. Dynamic cine multidetector CT images in nine patients were excluded. Maximal inspiratory, dynamic expiratory, and end-expiratory tracheal luminal areas were compared (Student t test) and correlated (Spearman rank) with PFT results and severity of parenchymal lung disease. RESULTS: Mean predicted forced expiratory volume in 1 second (FEV(1)) was 70.6% +/- 20.7, and mean Bhalla CT score was 41.8% +/- 13.6. In patients with CF, dynamic cine mean tracheal cross-sectional area reduction was 51.7% +/- 18.4 (range, 9%-89%) for forced expiratory maneuvers and 68.8% +/- 11.7 (range, 18%-88%) for coughing (P = .001). Tracheomalacia was demonstrated in 24 (69%) patients and no control subjects during forced expiratory maneuvers (P = .001) and in 10 (29%) patients and one (10%) control subject during coughing. For end-expiration images, mean tracheal luminal reduction was 16.1% +/- 14.0% (range, 0.0%-53.0%), with one patient demonstrating tracheal luminal reduction of more than 50%. There was no correlation between tracheal cross-sectional luminal reduction and either predicted FEV(1) or CT Bhalla score. CONCLUSION: Tracheomalacia depicted at dynamic cine multidetector CT is a highly prevalent finding in adults with CF. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/2522081956/DC1.
    • Treating moderate to severe psoriasis - best use of biologics.

      Lynch, Maeve; Kirby, Brian; Warren, Richard B; Dermatology Department, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. (2014-02)
      This review focuses on the efficacy, safety and best use of biologic agents in moderate-to-severe psoriasis. Recommendations from two recent guidelines are summarised. The NICE Guidelines 2012 provide recommendations on best practice for prescribing biologics. The German S3 Guidelines are based on a systematic review of published studies and report the efficacy of biologics and guidelines for treatment. Data on the safety of biologics are available for up to 5 years in psoriasis and are on the whole reassuring. Registry data is evolving and will provide data on safety to help inform long-term monitoring of patients with psoriasis on biologics agents. New anti-interleukin-17 (IL17) and anti-IL17RA biologics are in Phase 3 clinical trials and may prove to be more effective than existing biologics.
    • Treating pain in the emergency department.

      Kuan, Samuel C; Collins, Niamh C; Ryan, John M; Callanan, Ian; Emergency Department, St Vincent's University Hospital, Elm Park, Dublin 4,, Ireland. skuan02@hotmail.com (2012-02-01)
      The objective of this audit was to evaluate the impact of brief educational intervention on prompt recognition and treatment of pain in the emergency department. The audit was performed on all patients in the emergency department with pain presenting over a 24-h period on three occasions: preintervention, 1-week postintervention and at 4 months. In 151 patients, pain severity scores were mild (24%), moderate (42%), severe (16%) and unknown (18%). Pain score documentation at triage improved from 72 to 94% during the audit (P = 0.01). There was no significant difference in the number of patients treated within 20 min for severe pain (P = 0.076) and within 60 min for moderate pain (P = 0.796) between audits. The likelihood of receiving analgesia within 20 min increased with the patients' pain category (relative risk: 1.8 95% confidence interval: 1.4-2.3). Documentation of pain assessment and the use of pain scores at triage improved after a brief educational intervention but there was no measurable impact on treatment times.
    • Treatment and outcomes of anorectal melanoma.

      Heeney, Anna; Mulsow, Jurgen; Hyland, John M P; Department of Colorectal Surgery, St. Vincent's University Hospital, Dublin 4,, Ireland. annaheeney@rcsi.ie (2012-02-01)
      INTRODUCTION: anorectal melanoma is an uncommon disease constituting less than 3% of all melanomas. Due to its rarity, there are a lack of randomized control trials regarding appropriate management and current evidence is based mainly on retrospective studies. METHODS: in view of the controversial surgical treatment of anorectal melanoma, we review the most published literature in an attempt to elucidate its typical clinical features along with current thinking with respect to management approaches to this aggressive disease. Using the keywords "anorectal" and "malignant melanoma", a medline search of all articles in English was performed and the relevant articles procured. Additional references were retrieved by cross reference from key articles. RESULTS: anorectal melanoma affects the elderly with a slight preponderance for females. It commonly presents disguised as benign disease with local bleeding or suspicion for haemorrhoidal disease. There is no convincing evidence to indicate that radical resection of primary anorectal melanoma is associated with improvement in local control or survival, and local excision is an acceptable treatment option. CONCLUSION: optimum management depends on several factors and the therapeutic goals should be to lengthen survival and preserve quality-of-life. Given that wide local excision is a more limited intervention with comparable survival it should be considered as the initial treatment choice. Unfortunately prognosis for patients with this disease remains poor despite choice of treatment strategy with overall five year disease-free survival less than twenty percent in most studies.
    • Triad of emboli in acute flare of ulcerative colitis

      Kelly, ME; Dodd, J; Barry, M (Irish Medical Journal, 2014-05)
      Arterial thrombosis is rare in ulcerative colitis (UC). Our case report described a triad of arterial emboli in a UC patient who presented with bilateral lower limb claudication associated acute chest pain, confusion, ataxia and diplopia. Investigations confirmed bilateral femoral and popliteal artery occlusion, occipital infarct and a sub-endocardial infarct secondary to embolic disease.
    • Tumor budding is a strong and reproducible prognostic marker in T3N0 colorectal cancer.

      Wang, Lai Mun; Kevans, David; Mulcahy, Hugh; O'Sullivan, Jacintha; Fennelly, David; Hyland, John; O'Donoghue, Diarmuid; Sheahan, Kieran; Department of Histopathology & Centre for Colorectal Disease, St Vincent's, University Hospital, Dublin, Ireland. (2012-02-01)
      BACKGROUND: Tumor budding along the advancing front of colorectal adenocarcinoma is an early event in the metastatic process. A reproducible, prognostic budding scoring system based on outcomes in early stage colorectal cancer has not been established. DESIGN: One hundred twenty-eight T3N0M0 colorectal carcinoma patients with known outcome were identified. Tumor budding was defined as isolated tumor cells or clusters of <5 cells at the invasive tumor front. Tumor bud counts were generated in 5 regions at 200x by 2 pathologists (conventional bud count method). The median bud count per case was used to divide cases into low (median=0) and high budding (median > or =1) groups. Forty cases were reevaluated to assess reproducibility using the conventional and a novel rapid bud count method. RESULTS: Fifty-seven (45%) carcinomas had high and 71 (55%) had low budding scores. High budding was associated with an infiltrative growth pattern (P<0.0001) and lymphovascular invasion (P=0.005). Five-year cancer-specific survival was significantly poorer in high compared with low budding groups: 63% versus 91%, respectively, P<0.0001. Multivariate analysis demonstrated tumor budding to be independently prognostic (hazard ratio=4.76, P<0.001). Interobserver agreement was at least equivalent comparing the conventional to the rapid bud count methods: 87.5% agreement (kappa=0.75) versus 92.5% agreement (kappa=0.85), respectively. CONCLUSIONS: Tumor budding is a strong, reproducible, and independent prognostic marker of outcome that is easily assessed on hematoxylin and eosin slides. This may be useful for identifying the subset of T3N0M0 patients at high risk of recurrence who may benefit from adjuvant therapy.
    • Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report.

      Duffy, M J; Sturgeon, C; Lamerz, R; Haglund, C; Holubec, V L; Klapdor, R; Nicolini, A; Topolcan, O; Heinemann, V; Department of Pathology and Laboratory Medicine, St Vincent's University, Hospital, Dublin. michael.j.duffy@ucd.ie (2012-02-01)
      Pancreatic ductal adenocarcinoma is one of the most difficult malignancies to diagnose and treat. The aim of this article is to review how tumor markers can aid the diagnosis and management of patients with this malignancy. The most widely used and best validated marker for pancreatic cancer is CA 19-9. Inadequate sensitivity and specificity limit the use of CA 19-9 in the early diagnosis of pancreatic cancer. In non-jaundiced patients, however, CA 19-9 may complement other diagnostic procedures. In patients with resectable pancreatic cancer, presurgical and postresection CA 19-9 levels correlate with overall survival. In advanced disease, elevated pretreatment levels of CA 19-9 are associated with adverse patient outcome and thus may be combined with other factors for risk stratification. Most, but not all, reports indicate that serial levels of CA 19-9 correlate with response to systemic therapy. Use of CA 19-9 kinetics in conjunction with imaging is therefore recommended in monitoring therapy. Although several potential serum and tissue markers for pancreatic cancer are currently undergoing evaluation, none are sufficiently validated for routine clinical use. CA 19-9 thus remains the serum pancreatic cancer marker against which new markers for this malignancy should be judged.
    • Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

      Michielsen, Adriana J; Hogan, Andrew E; Marry, Joseph; Tosetto, Miriam; Cox, Fionnuala; Hyland, John M; Sheahan, Kieran D; O'Donoghue, Diarmuid P; Mulcahy, Hugh E; Ryan, Elizabeth J; et al. (2011)
      Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.