• Longitudinal assessment of thrombin generation potential in response to alteration of antiplatelet therapy after TIA or ischaemic stroke.

      Tobin, W O; Kinsella, J A; Kavanagh, G F; O'Donnell, J S; McGrath, R A; Collins, D R; Coughlan, T; O'Neill, D; Egan, B; Tierney, S; et al. (2013-02)
      The impact of changing antiplatelet therapy on thrombin generation potential in patients with ischaemic cerebrovascular disease (CVD) is unclear. We assessed patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Thrombin generation was assessed in platelet poor plasma. Ninety-one patients were recruited. Twenty-four were initially assessed on no antiplatelet therapy, and then after 14d (N = 23) and 90d (N = 8) on aspirin monotherapy; 52 were assessed on aspirin monotherapy, and after 14 and 90 days on aspirin and dipyridamole combination therapy; 21 patients were assessed on aspirin and after 14 days (N = 21) and 90 days (N = 19) on clopidogrel. Peak thrombin generation and endogenous thrombin potential were reduced at 14 and 90 days (p ≤ 0.04) in the overall cohort. We assessed the impact of individual antiplatelet regimens on thrombin generation parameters to investigate the cause of this effect. Lag time and time-to-peak thrombin generation were unchanged at 14 days, but reduced 90 days after commencing aspirin (p ≤ 0.009). Lag time, peak thrombin generation and endogenous thrombin potential were reduced at both 14 and 90 days after adding dipyridamole to aspirin (p ≤ 0.01). Lag time was reduced 14 days after changing from aspirin to clopidogrel (p = 0.045), but this effect was not maintained at 90 days (p = 0.2). This pilot study did not show any consistent effects of commencing aspirin, or of changing from aspirin to clopidogrel on thrombin generation potential during follow-up. The addition of dipyridamole to aspirin led to a persistent reduction in peak and total thrombin generation ex vivo, and illustrates the diverse, potentially beneficial, newly recognised 'anti-coagulant' effects of dipyridamole in ischaemic CVD.
    • Longitudinal genotyping of Candida dubliniensis isolates reveals strain maintenance, microevolution, and the emergence of itraconazole resistance.

      Fleischhacker, M; Pasligh, J; Moran, G; Ruhnke, M; Charitè-Universitätsmedizin Berlin Medizinische Klinik m.S. Onkologie u. Hämatologie, Mol. Biol. Labor, Alte Apotheke, CCM, Charitèplatz 1, 10117 Berlin, Germany. michael.fleischhacker@charite.de (2010-05)
      We investigated the population structure of 208 Candida dubliniensis isolates obtained from 29 patients (25 human immunodeficiency virus [HIV] positive and 4 HIV negative) as part of a longitudinal study. The isolates were identified as C. dubliniensis by arbitrarily primed PCR (AP-PCR) and then genotyped using the Cd25 probe specific for C. dubliniensis. The majority of the isolates (55 of 58) were unique to individual patients, and more than one genotype was recovered from 15 of 29 patients. A total of 21 HIV-positive patients were sampled on more than one occasion (2 to 36 times). Sequential isolates recovered from these patients were all closely related, as demonstrated by hybridization with Cd25 and genotyping by PCR. Six patients were colonized by the same genotype of C. dubliniensis on repeated sampling, while strains exhibiting altered genotypes were recovered from 15 of 21 patients. The majority of these isolates demonstrated minor genetic alterations, i.e., microevolution, while one patient acquired an unrelated strain. The C. dubliniensis strains could not be separated into genetically distinct groups based on patient viral load, CD4 cell count, or oropharyngeal candidosis. However, C. dubliniensis isolates obtained from HIV-positive patients were more closely related than those recovered from HIV-negative patients. Approximately 8% (16 of 194) of isolates exhibited itraconazole resistance. Cross-resistance to fluconazole was only observed in one of these patients. Two patients harboring itraconazole-resistant isolates had not received any previous azole therapy. In conclusion, longitudinal genotyping of C. dubliniensis isolates from HIV-infected patients reveals that isolates from the same patient are generally closely related and may undergo microevolution. In addition, isolates may acquire itraconazole resistance, even in the absence of prior azole therapy.
    • Longitudinal study of aortic isthmus Doppler in appropriately grown and small-for-gestational-age fetuses with normal and abnormal umbilical artery Doppler.

      Kennelly, M M; Farah, N; Hogan, J; Reilly, A; Turner, M J; Stuart, B; Ultrasound and Fetal Medicine Centre, Coombe Women and Infants University Hospital, Dublin, Ireland. mkennelly@doctors.org.uk (2012-04)
      To establish reference ranges using longitudinal data for aortic isthmus (AoI) Doppler indices in appropriate-for-gestational-age (AGA) fetuses and to document the longitudinal trends in a cohort of small-for-gestational-age (SGA) fetuses with normal umbilical artery Doppler and in fetuses with intrauterine growth restriction (IUGR) and abnormal umbilical artery Doppler.
    • Looking in the mouth for Crohn's disease.

      Rowland, Marion; Fleming, Paddy; Bourke, Billy; UCD School of Medicine & Medical Science, Crumlin, Dublin, Ireland. (2010-02)
      It is widely acknowledged among gastroenterologists that the oral cavity may be involved in Crohn's disease (CD). However, the specific manifestations are poorly appreciated. Although oral aphthous ulceration is probably not diagnostically useful in patients with suspected CD, disease-specific manifestations do occur and are particularly common in children presenting with CD. These manifestations can be subtle, often are subclinical, yet commonly harbor diagnostically useful material (granulomas). Orofacial granulomatosis (OFG) is conventionally used to describe patients with overt oral disease without obvious involvement of the gastrointestinal tract. However, many patients with OFG have subclinical intestinal CD or will progress to develop overt intestinal CD with time. The management of severe oral disease is challenging and lacks a clear evidence base.
    • Looking in the mouth for Crohn's disease.

      Rowland, Marion; Fleming, Paddy; Bourke, Billy; UCD School of Medicine & Medical Science, Crumlin, Dublin, Ireland. (2012-02-01)
      It is widely acknowledged among gastroenterologists that the oral cavity may be involved in Crohn's disease (CD). However, the specific manifestations are poorly appreciated. Although oral aphthous ulceration is probably not diagnostically useful in patients with suspected CD, disease-specific manifestations do occur and are particularly common in children presenting with CD. These manifestations can be subtle, often are subclinical, yet commonly harbor diagnostically useful material (granulomas). Orofacial granulomatosis (OFG) is conventionally used to describe patients with overt oral disease without obvious involvement of the gastrointestinal tract. However, many patients with OFG have subclinical intestinal CD or will progress to develop overt intestinal CD with time. The management of severe oral disease is challenging and lacks a clear evidence base.
    • Loss of chromosome 1p/19q in oligodendroglial tumors: refinement of chromosomal critical regions and evaluation of internexin immunostaining as a surrogate marker.

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

      O'Connor, Laserina (Nursing in General Practice, 2016-02)
      Introduction Low back pain, or back pain is a leading cause of disability worldwide1, threatening function, mental health and quality of life2,3 and is managed mostly within primary care. In the Republic of Ireland (ROI) approximately 35.5% of the population experiences chronic pain.4,5 Back pain is the most common cause of chronic pain in Europe6 as well as in the ROI (47.6%).4
    • Low body mass index in adolescent idiopathic scoliosis: relationship with pre- and postsurgical factors.

      Tarrant, R C; Lynch, Sam; Sheeran, Padraig; O'Loughlin, Padhraig F; Harrington, Michelle; Moore, David P; Kiely, Patrick J; Department of Orthopaedic Surgery, Our Lady's Children's Hospital, Crumlin, Dublin (Lippincott Williams & Wilkins, 2014-01-15)
      Retrospective cohort study. OBJECTIVE: To determine the association between low preoperative body mass index (BMI) and outcome of spinal fusion in adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Several studies report a lower weight and BMI in untreated subjects with AIS than nonscoliotic age-matched controls. However, very little is known about the clinical impact of low BMI on pre- or postsurgical parameters in this patient group. METHODS: Seventy-seven eligible patients with AIS who underwent 1-stage posterior spinal fusion and correction at 2 tertiary centers (January 2010-April 2012) were included. Preoperative weight, corrected height, and BMI values were converted to z scores using the British 1990 growth reference data. Relationships between anthropometric indices and comorbidities, laboratory blood data, radiographical outcomes, length of hospital stay, and perioperative complications were examined, and the independent factors associated with low BMI (z score < -1) evaluated using binary logistic regression analysis. RESULTS: In this AIS cohort (mean age, 15.04 yr; n = 72 females), 21 subjects (27.3%) had a low preoperative BMI; of these, 5 cases (6.5%) were considered severely thin. Lower BMI and weight z scores correlated with a greater percent correction of thoracic curves (rs = -0.287 and rs = -0.257, respectively, P < 0.05). In both the univariate and multivariate regression analysis, low BMI was significantly associated with preoperative asthma incidence (adjusted odds ratio 5.33, P = 0.023) and prolonged prothrombin time (adjusted odds ratio 4.53, P = 0.027), in addition to postoperative ileus development (adjusted odds ratio 11.96, P = 0.019). Preoperative Cobb angle, estimated intraoperative blood loss and length of hospital stay did not significantly differ between the BMI groups. CONCLUSION: Significantly increased preoperative coagulation abnormality and asthma incidence as well as a greater percent correction of thoracic curves were associated with low BMI in this series. It was also found that postoperative ileus was independently associated with low BMI.Level of Evidence: 3.
    • A Low Glycaemic Index Diet in Pregnancy Induces DNA Methylation Variation in Blood of Newborns: Results from the ROLO Randomised Controlled Trial.

      Geraghty, Aisling A; Sexton-Oates, Alexandra; O'Brien, Eileen C; Alberdi, Goiuri; Fransquet, Peter; Saffery, Richard; McAuliffe, Fionnuala M; National Maternity Hospital Holles Street Dublin, University College Dublin, Cancer and Disease Epigenetics, Murdoch Children's Research Institute, Melbourne, Victoria, Aus, Department of Paediatrics, University of Melbourne, Victoria, Aus (MDPI, 2018-04-06)
      The epigenetic profile of the developing fetus is sensitive to environmental influence. Maternal diet has been shown to influence DNA methylation patterns in offspring, but research in humans is limited. We investigated the impact of a low glycaemic index dietary intervention during pregnancy on offspring DNA methylation patterns using a genome-wide methylation approach. Sixty neonates were selected from the ROLO (Randomised cOntrol trial of LOw glycaemic index diet to prevent macrosomia) study: 30 neonates from the low glycaemic index intervention arm and 30 from the control, whose mothers received no specific dietary advice. DNA methylation was investigated in 771,484 CpG sites in free DNA from cord blood serum. Principal component analysis and linear regression were carried out comparing the intervention and control groups. Gene clustering and pathway analysis were also explored. Widespread variation was identified in the newborns exposed to the dietary intervention, accounting for 11% of the total level of DNA methylation variation within the dataset. No association was found with maternal early-pregnancy body mass index (BMI), infant sex, or birthweight. Pathway analysis identified common influences of the intervention on gene clusters plausibly linked to pathways targeted by the intervention, including cardiac and immune functioning. Analysis in 60 additional samples from the ROLO study failed to replicate the original findings. Using a modest-sized discovery sample, we identified preliminary evidence of differential methylation in progeny of mothers exposed to a dietary intervention during pregnancy.
    • Low glycaemic index diet in pregnancy to prevent macrosomia (ROLO study): randomised control trial.

      Walsh, Jennifer M; McGowan, Ciara A; Mahony, Rhona; Foley, Michael E; McAuliffe, Fionnuala M; UCD Obstetrics and Gynaecology, School of Medicine and Medical Science, University College Dublin, National Maternity Hospital, Dublin, Ireland. (2012-08)
      To determine if a low glycaemic index diet in pregnancy could reduce the incidence of macrosomia in an at risk group.
    • Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer.

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

      Cotter, Meaghan P; Smyth, Elizabeth; O'Gorman, Joanne; Browne, Sarah; Hickey, David P; Humphreys, Hilary; Department of Microbiology, Beaumont Hospital, Dublin, Ireland. mcotter@mater.ie (2012-12)
      Infection following transplantation is a cause of morbidity and mortality. Perfusion fluid (PF) used to preserve organs between recovery and transplantation represents a medium suitable for the growth of microbes. We evaluated the relevance of positive growth from PF sampled before the implantation of kidney or kidney-pancreas (KP) allografts.
    • Low risk of inhibitor formation in haemophilia A patients following en masse switch in treatment to a third generation full length plasma and albumin-free recombinant factor VIII product (ADVATE®).

      Bacon, C L; Singleton, E; Brady, B; White, B; Nolan, B; Gilmore, R M; Ryan, C; Keohane, C; Jenkins, P Vince; O'Donnell, J S; et al. (2011-05)
      Previous studies have suggested that development of inhibitors in previously treated patients (PTPs) may be attributable to a switch in factor VIII (FVIII) therapeutic product. Consequently, it is widely recognized that inhibitor development must be assessed in PTPs following the introduction of any new FVIII product. Following a national tender process in 2006, all patients with haemophilia A in Ireland changed their FVIII treatment product en masse to a plasma and albumin-free recombinant full-length FVIII product (ADVATE(®)). In this study, we retrospectively reviewed the case records of Irish PTPs to evaluate risk of inhibitor formation following this treatment switch. One hundred and thirteen patients participated in the study. Most patients (89%) had severe haemophilia. Only one of 96 patients with no inhibitor history developed an inhibitor. Prior to the switch in his recombinant FVIII (rFVIII) treatment of choice, this child had only experienced three exposure days (EDs). Consequently, in total he had only received 6 EDs when his inhibitor was first diagnosed. In keeping with this lack of de novo inhibitor development, we observed no evidence of any recurrent inhibitor formation in any of 16 patients with previously documented inhibitors. Similarly, following a previous en masse switch, we have previously reported that changing from a Chinese hamster ovary cell-produced to a baby hamster kidney cell-produced rFVIII was also associated with a low risk of inhibitor formation in PTPs. Our cumulative findings from these two studies clearly emphasizes that the risk of inhibitor development for PTPs following changes in commercial rFVIII product is low, at least in the Irish population.
    • Low total cortisol correlates closely with low free cortisol in traumatic brain injury and predicts mortality and long-term hypopituitarism

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

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

      Murphy, Colin G; Butler, Joseph S; Green, Connor; Egan, Bridget M; Sparkes, Joseph; Department of Trauma and Orthopaedic Surgery, Adelaide and Meath Hospital Incorporating, The National Children's Hospital, Tallaght, Dublin, Ireland. cmurphy@rcsi.ie (2013-02)
    • Lower segment cesarean scar rupture: does it always occur in the next labour

      Corrigan, L; O' Herlihy, C; McGoldrick, A (American Journal of Obstetrics and Gynaecology, 2012-01)
      32nd Annual Meeting - Society for Maternal-Fetal Medicine. The Pregnancy Meeting 6-11 February 2012 Dallas, Texas USA
    • Lumbar Morel-Lavallée effusion.

      Moran, Deirdre E; Napier, Nicholas A; Kavanagh, Eoin C; Department of Radiology, Cappagh National Orthopaedic Hospital, Finglas, Dublin 11, Ireland. (The spine journal : official journal of the North American Spine Society, 2012-12)