• Safe surgery: how accurate are we at predicting intra-operative blood loss?

      Surgical Registrar Medical Student Consultant Colorectal Surgeon, Department of, Surgery, Beaumont Hospital, Dublin, Ireland. (2012-02-01)
      Introduction Preoperative estimation of intra-operative blood loss by both anaesthetist and operating surgeon is a criterion of the World Health Organization's surgical safety checklist. The checklist requires specific preoperative planning when anticipated blood loss is greater than 500 mL. The aim of this study was to assess the accuracy of surgeons and anaesthetists at predicting intra-operative blood loss. Methods A 6-week prospective study of intermediate and major operations in an academic medical centre was performed. An independent observer interviewed surgical and anaesthetic consultants and registrars, preoperatively asking each to predict expected blood loss in millilitre. Intra-operative blood loss was measured and compared with these predictions. Parameters including the use of anticoagulation and anti-platelet therapy as well as intra-operative hypothermia and hypotension were recorded. Results One hundred sixty-eight operations were included in the study, including 142 elective and 26 emergency operations. Blood loss was predicted to within 500 mL of measured blood loss in 89% of cases. Consultant surgeons tended to underestimate blood loss, doing so in 43% of all cases, while consultant anaesthetists were more likely to overestimate (60% of all operations). Twelve patients (7%) had underestimation of blood loss of more than 500 mL by both surgeon and anaesthetist. Thirty per cent (n = 6/20) of patients requiring transfusion of a blood product within 24 hours of surgery had blood loss underestimated by more than 500 mL by both surgeon and anaesthetist. There was no significant difference in prediction between patients on anti-platelet or anticoagulation therapy preoperatively and those not on the said therapies. Conclusion Predicted intra-operative blood loss was within 500 mL of measured blood loss in 89% of operations. In 30% of patients who ultimately receive a blood transfusion, both the surgeon and anaesthetist significantly underestimate the risk of blood loss by greater than 500 mL. Theatre staff must be aware that 1 in 14 patients undergoing intermediate or major surgery will have an unexpected blood loss exceeding 500 mL and so robust policies to identify and manage such circumstances should be in place to improve patient safety.
    • A Salbutamol responsive myopathy

      Fitzpatrick, A; Walsh, R; Hardiman, O; McConville, J (2011-05)
      Background: Reversibility of weakness is rare in inherited muscle disease and suggests a channelopathy as the underlying pathology. Improvement in muscle strength after treatment with beta-adrenergic agonists has been documented in hyperkalaemic periodic paralysis and only very recently in the congenital myasthenic syndromes. The exact mechanism of action is not understood. Case description: Case A, the second youngest of 10 siblings from a non-consanguineous Irish kindred, presented at the age of 46 years with mild limb-girdle muscle weakness with no other symptoms and no demonstrable fatiguability. Three siblings were similarly affected (2/3 were examined, 1/3 died before examination from unrelated causes). Case B and C reported first symptoms aged 62 and 45 respectively. All 3 remained independently mobile with a waddling gait after follow up of between 11 and 25 years from first symptoms. Case A reported marked improvement in function after a short course of inhaled Salbutamol prescribed by his GP. On oral Salbutamol treatment limb-girdle strength returned to MRC grade 5, but deteriorated to MRC grade 4 when treatment was stopped. The other siblings showed similar response. Results: Initial investigation of cases A and B revealed slightly elevated creatinine kinase (CK: 307; CK:283) and some fibre atrophy and type II predominance on muscle biopsy. Case B showed 16% decrement on repetitive nerve stimulation but the others had no abnormality on neurophysiological examination. Homozygous c.1143dupC mutations in exon of the DOK7 gene were found in all three affected cases confirming a Dok-7 congenital myasthenic syndrome. Discussion: The Dok-7 CMS phenotype is that of a predominantly limb-girdle muscle weakness and a characteristic waddling gait; fatiguability may be very subtle and so these cases may be mistaken for congenital myopathy. The serendipitous prescription of Salbutamol was the clue to a myasthenic pathology in this kindred. Dok-7 CMS has been reported with adult onset but 62 years is the latest reported age at onset to date.
    • Screening of hypoxia-inducible genes in sporadic ALS.

      Cronin, Simon; Greenway, Matthew J; Andersen, Peter M; Hardiman, Orla; Department of Neurology, Beaumont Hospital, Dublin, Ireland. (2008-10)
      Genetic variations in two hypoxia-inducible angiogenic genes, VEGF and ANG, have been linked with sporadic amyotrophic lateral sclerosis (SALS). Common variations in these genes may reduce the levels or functioning of their products. VEGF and ANG belong to a larger group of angiogenic genes that are up-regulated under hypoxic conditions. We hypothesized that common genetic variation across other members of this group may also predispose to sporadic ALS. To screen other hypoxia-inducible angiogenic genes for association with SALS, we selected 112 tagging single nucleotide polymorphisms (tgSNPs) that captured the common genetic variation across 16 VEGF-like and eight ANG-like hypoxia-inducible genes. Screening for association was performed in 270 Irish individuals with typical SALS and 272 ethnically matched unrelated controls. SNPs showing association in the Irish phase were genotyped in a replication sample of 281 Swedish sporadic ALS patients and 286 Swedish controls. Seven markers showed association in the Irish. The one modest replication signal observed in the Swedish replication sample, at rs3801158 in the gene inhibin beta A, was for the opposite allele vs. the Irish cohort. We failed to detect association of common variation across 24 candidate hypoxia-inducible angiogenic genes with SALS.
    • Screening of siRNA nanoparticles for delivery to airway epithelial cells using high-content analysis

      Hibbitts, Alan; Lieggi, Nora; McCabe, Olive; Thomas, Warren; Barlow, James; O’Brien, Fiona; Cryan, Sally-Ann (2011-08)
      Aims: Delivery of siRNA to the lungs via inhalation offers a unique opportunity to develop a new treatment paradigm for a range of respiratory conditions. However, progress has been greatly hindered by safety and delivery issues. This study developed a high-throughput method for screening novel nanotechnologies for pulmonary siRNA delivery. Methodology: Following physicochemical analysis, the ability of PEI–PEG–siRNA nanoparticles to facilitate siRNA delivery was determined using high-content analysis (HCA) in Calu-3 cells. Results obtained from HCA were validated using confocal microscopy. Finally, cytotoxicity of the PEI–PEG–siRNA particles was analyzed by HCA using the Cellomics® multiparameter cytotoxicity assay. Conclusion: PEI–PEG–siRNA nanoparticles facilitated increased siRNA uptake and luciferase knockdown in Calu-3 cells compared with PEI–siRNA.
    • Sealed Orifice Laparoscopic or Endoscopic (SOLE) Surgery: technology and technique convergence for next-step colorectal surgery.

      Cahill, R A; Hompes, R; Cunningham, C; Mortensen, N J; Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland., cahillra@gmail.com (2012-02-01)
      The new avenue of minimally invasive surgery, referred to as single-incision/access laparoscopy, is often presented as an alternative to standard multiport approaches, whereas in fact it is more usefully perceived as a complementary modality. The emergence of the technique can be of greater use both to patients and to the colorectal specialty if its principles can be merged into next-stage evolution by synergy with more conventional practice. In particular, rather than device specificity, what is needed is convergence of capability that can be applied by the same surgeon in differing scenarios depending on the individualized patient and disease characteristics. We detail here the global applicability of a simple access device construct that allows the provision of simple and complex single-port laparoscopy as well as contributing to multiport laparoscopic and transanal resections in a manner that is reliable, reproducible, ergonomical and economical.
    • Seasonal Variation in the Emergency Department Prevalence Of Sepsis

      McNevin, C; McDowell, R; Ni Shearcaigh, A; Wakai, A (Irish Medical Journal, 2018-05)
      The incidence and mortality of sepsis and severe sepsis in hospitalised patients is seasonal and consistently highest during the winter. The primary aim of this study was to measure the seasonal variation in the prevalence of emergency department (ED) patients with sepsis. This cross-sectional study was performed over two four-week periods in the summer and in the winter, respectively. The clinical records of all patients presenting to the ED during the study periods were retrospectively screened to determine if they met the criteria for “uncomplicated” sepsis and severe sepsis or septic shock. The prevalence of “uncomplicated” sepsis was higher in the winter (43.9 per 1000) compared to the summer (30.7 per 1000). The prevalence of severe sepsis or septic shock was also higher in the winter (17.7 per 1000) compared to the summer (11.7 per 1000). This quantitatively demonstrates the increased ED burden of sepsis in the winter that can be used to inform healthcare planning and resource allocation.
    • Secondary prevention after ischaemic stroke: the ASPIRE-S study

      Brewer, Linda; Mellon, Lisa; Hall, Patricia; Dolan, Eamon; Horgan, Frances; Shelley, Emer; Hickey, Anne; Williams, David (BMC Neurology, 2015-10-23)
    • Secondary resistance to cabergoline therapy in a macroprolactinoma: a case report and literature review.

      Behan, L A; Draman, M S; Moran, C; King, T; Crowley, R K; O'Sullivan, E P; Smith, D; Thompson, C J; Agha, A; Department of Academic Endocrinology and Diabetes, Beaumont Hospital and RCSI Medical School, Dublin 9, Ireland, lucyannbehan@beaumont.i.e. (2009-02-04)
      Primary resistance to dopamine agonists occurs in 10-15% of prolactinomas but secondary resistance following initial biochemical and anti-proliferative response is very rare and has only been hitherto described in four previous cases, two with bromocriptine and two with cabergoline. We describe a case of a 57-year-old woman who presented with a large macroprolactinoma with suprasellar extension. She was initially treated with bromocriptine therapy with a resolution of symptoms, marked reduction in prolactin concentration and complete tumour shrinkage; a response which was subsequently maintained on cabergoline. After 8 years of dopamine agonist therapy, her prolactin concentration began to rise and there was symptomatic recurrence of her tumour despite escalating doses of cabergoline up to 6 mg weekly. Non-compliance was outruled by observed inpatient drug administration. The patient underwent surgical debulking followed by radiotherapy with good response. This case adds to the previous two cases of secondary resistance to cabergoline therapy in prolactinomas a marked initial response. While the mechanism of secondary resistance remains unknown and not possible to predict, close observation of prolactinoma patients on treatment is necessary.
    • Secondary resistance to cabergoline therapy in a macroprolactinoma: a case report and literature review.

      Behan, L A; Draman, M S; Moran, C; King, T; Crowley, R K; O'Sullivan, E P; Smith, D; Thompson, C J; Agha, A; Department of Academic Endocrinology and Diabetes, Beaumont Hospital and RCSI, Medical School, Dublin 9, Ireland. lucyannbehan@beaumont.i.e (2012-02-01)
      Primary resistance to dopamine agonists occurs in 10-15% of prolactinomas but secondary resistance following initial biochemical and anti-proliferative response is very rare and has only been hitherto described in four previous cases, two with bromocriptine and two with cabergoline. We describe a case of a 57-year-old woman who presented with a large macroprolactinoma with suprasellar extension. She was initially treated with bromocriptine therapy with a resolution of symptoms, marked reduction in prolactin concentration and complete tumour shrinkage; a response which was subsequently maintained on cabergoline. After 8 years of dopamine agonist therapy, her prolactin concentration began to rise and there was symptomatic recurrence of her tumour despite escalating doses of cabergoline up to 6 mg weekly. Non-compliance was outruled by observed inpatient drug administration. The patient underwent surgical debulking followed by radiotherapy with good response. This case adds to the previous two cases of secondary resistance to cabergoline therapy in prolactinomas a marked initial response. While the mechanism of secondary resistance remains unknown and not possible to predict, close observation of prolactinoma patients on treatment is necessary.
    • Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency.

      Kelly, Emer; Greene, Catherine M; Carroll, Tomás P; McElvaney, Noel G; O'Neill, Shane J; Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. (2009-06-19)
      Z alpha(1)-antitrypsin (ZAAT) deficiency is a disease associated with emphysematous lung disease and also with liver disease. The liver disease of AAT deficiency is associated with endoplasmic reticulum (ER) stress. SEPS1 is a selenoprotein that, through a chaperone activity, decreases ER stress. To determine the effect of SEPS1 on ER stress in ZAAT deficiency, we measured activity of the grp78 promoter and levels of active ATF6 as markers of the unfolded protein response in HepG2 cells transfected with the mutant form of AAT, a ZAAT transgene. We evaluated levels of NFkappaB activity as a marker of the ER overload response. To determine the effect of selenium supplementation on the function of SEPS1, we investigated glutathione peroxidase activity, grp78 promoter activity, and NFkappaB activity in the presence or absence of selenium. SEPS1 reduced levels of active ATF6. Overexpression of SEPS1 also inhibited grp78 promoter and NFkappaB activity, and this effect was enhanced in the presence of selenium supplementation. This finding demonstrates a role for SEPS1 in ZAAT deficiency and suggests a possible therapeutic potential for selenium supplementation.
    • Self reporting of symptoms and delays in patients presenting to a rapid access lung cancer clinic (RALCC)

      Geraghty, Colm; Uzbeck, Mateen; Dunican, Eleanor (2011-06)
      Introduction: The RALCC at our hospital is aimed at expediting the diagnosis of suspected thoracic malignancies. Methods: A self-reported questionnaire to consecutive patients on their first visit. Patient‘s perception of why they were attending, symptoms, duration before seeking medical attention, time to referral and risks for lung cancer recorded. Results: 154 patients, 81 male, 73 female, mean age 63 years (21-86). GP‘s made most referrals 87% and 68% perceived abnormal radiology as reason for attendance. Majority were symptomatic 88.6% with 57% reporting ≥3 symptoms. Cough was most common presenting symptom 61%, fatigue 52%, dyspnoea 45%, chest infection 45%, chest pain 40%, weight loss 32% and haemoptysis 25%. Haemoptysis had the least delay in presenting to a health care provider (mean 30 days, range 2-120) whereas for cough, dyspnoea and chest pain mean dealy was 4.5 months. Average delay in seeking medical attention and referral to RALLC was 14 weeks. 72% were current or ex-smokers and 21% reported at least one first degree relative with lung cancer. Conclusions: significant delays exist between symptom onset and presentation to a health care provider and depends on symptom type. The bulk of the delay was before patients sought medical attention but there was still a sizeable delay between presentation and referral toRALCC. One in 5 patients had a first degree relative with lung cancer indicating that this may have been a factor in the decision to refer. Our study highlights the need for increased public awareness regarding the presenting symptoms of lung cancer and there exists the opportunity to reduce delays in diagnosis resulting in better outcomes.
    • Self-regulation of unattainable goals in suicide attempters: the relationship between goal disengagement, goal reengagement and suicidal ideation.

      O'Connor, Rory C; Fraser, Louisa; Whyte, Marie-Claire; MacHale, Siobhan; Masterton, George; Suicidal Behaviour Research Group, Department of Psychology, University of Stirling, Stirling FK9 4LA, UK. ro2@stir.ac.uk (2009-02)
      There is growing interest in models of adaptive self-regulation. Recent research suggests that goal disengagement and goal reengagement (i.e., goal adjustment) are implicated in the self-regulation of emotion. This study extends the self-regulation research to investigate the utility of goal adjustment in understanding suicidal risk. To this end, two hundred adults hospitalised following a suicidal episode completed a range of clinical and psychological measures in hospital and were followed up approximately 2.5 months after discharge (Time 2). Hierarchical regression analyses showed that goal reengagement predicted suicidal ideation at Time 2. In addition, the lack of goal reengagement was especially pernicious when reported concomitantly with high disengagement. These predictive effects were independent of baseline mood, attempt status and suicidal intent. The theoretical and clinical implications are discussed.
    • Severe abdominal injuries sustained in an adult wearing a pelvic seatbelt: a case report and review of the literature.

      O'Kelly, F; O'Brien, G C; Broe, P J; Department of Academic Surgery, Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin, Ireland. (2008-12)
      In automobile accidents, the "seatbelt syndrome" (SBS) consists of a constellation of injuries, predominantly involving thoraco-lumbar vertebral fractures and intraabdominal organ injury. A recent amendment to Irish legislation has made the wearing of seatbelts mandatory for all rear seated passengers in an effort to protect children. Whilst rear seatbelts result in a significant reduction in morbidity and mortality following road traffic accidents (RTA), we present a case in which the rear lap seatbelt caused severe abdominal injuries. It is evident that the current rear seat lapbelt system is an inferior design associated with a significant morbidity and mortality when compared to three-point harness system and consideration should be given to replacing them in all motor vehicles.
    • Severe hand injuries resulting from Samurai sword assaults: a Dublin case series.

      Seoighe, Deirdre M; O'Neill, Anne C; Eadie, Patricia A (2011-01)
    • Severe rhabdomyolysis as a consequence of the interaction of fusidic acid and atorvastatin.

      Magee, Ciara N; Medani, Samar A; Leavey, Sean F; Conlon, Peter J; Clarkson, Michael R; Department of Nephrology, Beaumont Hospital, Dublin, Ireland. (2010-11)
      Rhabdomyolysis is a known complication of statin therapy and may be triggered by a pharmacokinetic interaction between a statin and a second medication. Fatal statin-induced rhabdomyolysis has an incidence of 0.15 deaths/million prescriptions. We describe 4 cases of severe rhabdomyolysis with the common feature of atorvastatin use and coadministration of fusidic acid. All cases involved long-term therapy with atorvastatin; fusidic acid was introduced for treatment of osteomyelitis or septic arthritis. Three cases occurred in the setting of diabetes mellitus, with 2 in patients with end-stage renal disease, suggesting increased susceptibility to atorvastatin-fusidic acid-induced rhabdomyolysis in these patient populations. Of the 4 patients in this series, 3 died. Fusidic acid is a unique bacteriostatic antimicrobial agent with principal antistaphylococcal activity. There have been isolated reports of rhabdomyolysis attributed to the interaction of statins and fusidic acid, the cause of which is unclear. Fusidic acid does not inhibit the cytochrome P450 3A4 isoenzyme responsible for atorvastatin metabolism; increased atorvastatin levels due to inhibition of the glucuronidation pathway may be responsible. Considering the low frequency of fusidic acid use, the appearance of 4 such cases within a short time and in a small population suggests the probability that development of this potentially fatal complication may be relatively high.
    • Sex and estrous cycle-dependent rapid protein kinase signaling actions of estrogen in distal colonic cells.

      O'Mahony, Fiona; Harvey, Brian J; Department of Molecular Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. fomahony@rcsi.ie (2008-10)
      Previous studies from our laboratory demonstrated that 17beta-estradiol (E2) rapidly inhibits Cl(-) secretion in rat and human distal colonic epithelium. The inhibition has been shown to occur via targeting of a basolateral K(+) channel identified as the KCNQ1 (KvLQT1) channel. E2 indirectly modulates the channel activity via a cascade of second messengers which are rapidly phosphorylated in response to E2. The anti-secretory mechanism may be the manner by which E2 induces fluid retention in the intestine during periods of high circulating plasma E2. Here we review the sex-dependent and estrous cycle regulation of this novel rapid response to E2. The inhibition of KCNQ1 channel activity and Cl(-) secretion will be of interest in the future in the investigation of the retentive effects of estrogen in female tissue and also in the study of secretory disorders and drugable targets of the intestine.
    • Sexual dimorphism and oestrogen regulation of KCNE3 expression modulates the functional properties of KCNQ1 K channels.

      Alzamora, Rodrigo; O'Mahony, Fiona; Bustos, Viviana; Rapetti-Mauss, Raphael; Urbach, Valerie; Cid, L Pablo; Sepulveda, Francisco V; Harvey, Brian J; Department of Molecular Medicine, Education and Research Centre, Royal College of, Surgeons in Ireland, Beaumont Hospital, Dublin, Republic of Ireland. (2012-02-01)
      The KCNQ1 potassium channel associates with various KCNE ancillary subunits that drastically affect channel gating and pharmacology. Co-assembly with KCNE3 produces a current with nearly instantaneous activation, some time-dependent activation at very positive potentials, a linear current-voltage relationship and a 10-fold higher sensitivity to chromanol 293B. KCNQ1:KCNE3 channels are expressed in colonic crypts and mediate basolateral K(+) recycling required for Cl(-) secretion. We have previously reported the female-specific anti-secretory effects of oestrogen via KCNQ1:KCNE3 channel inhibition in colonic crypts. This study was designed to determine whether sex and oestrogen regulate the expression and function of KCNQ1 and KCNE3 in rat distal colon. Colonic crypts were isolated from Sprague-Dawley rats and used for whole-cell patch-clamp and to extract total RNA and protein. Sheets of epithelium were used for short-circuit current recordings. KCNE1 and KCNE3 mRNA and protein abundance were significantly higher in male than female crypts. No expression of KCNE2 was found and no difference was observed in KCNQ1 expression between male and female (at oestrus) colonic crypts. Male crypts showed a 2.2-fold higher level of association of KCNQ1 and KCNE3 compared to female cells. In female colonic crypts, KCNQ1 and KCNE3 protein expression fluctuated throughout the oestrous cycle and 17beta-oestradiol (E2 10 nM) produced a rapid (<15 min) dissociation of KCNQ1 and KCNE3 in female crypts only. Whole-cell K(+) currents showed a linear current-voltage relationship in male crypts, while K(+) currents in colonic crypts isolated from females displayed voltage-dependent outward rectification. Currents in isolated male crypts and epithelial sheets were 10-fold more sensitive to specific KCNQ1 inhibitors, such as chromanol 293B and HMR-1556, than in female. The effect of E2 on K(+) currents mediated by KCNQ1 with or without different beta-subunits was assayed from current-voltage relations elicited in CHO cells transfected with KCNQ1 and KCNE3 or KCNE1 cDNA. E2 (100 nM) reduced the currents mediated by the KCNQ1:KCNE3 potassium channel and had no effect on currents via KCNQ1:KCNE1 or KCNQ1 alone. Currents mediated by the complex formed by KCNQ1 and the mutant KCNE3-S82A beta-subunit (mutation of the site for PKCdelta-promoted phosphorylation and modulation of the activity of KCNE3) showed rapid run-down and insensitivity to E2. Together, these data suggest that oestrogen regulates the expression of the KCNE1 and KCNE3 and with it the gating and pharmacological properties of the K(+) conductance required for Cl(-) secretion. The decreased association of the KCNQ1:KCNE3 channel complex promoted by oestrogen exposure underlies the molecular mechanism for the sexual dimorphism and oestrous cycle dependence of the anti-secretory actions of oestrogen in the intestine.
    • Short term and long term effects of pulmonary rehabilitation on physical activity in COPD.

      Egan, Claire; Deering, Brenda M; Blake, Catherine; Fullen, Brona M; McCormack, Niamh M; Spruit, Martijn A; Costello, Richard W; Department of Respiratory Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland. (2012-12)
      The central purpose of pulmonary rehabilitation is to reduce morbidity by improving functional capacity through exercise. It is still unknown if improvements in functional capacity are maintained in the long-term and if this leads to increased physical activity levels as measured by a free-living activity monitor. The hypothesis of this study was that pulmonary rehabilitation would lead to a sustained increase in standard outcome measures and in daily physical activity.
    • Should incidental asymptomatic angiographic stenoses and occlusions be treated in patients with peripheral arterial disease?

      Keeling, Aoife N; Naughton, Peter A; Khalidi, Karim; Ayyoub, Alaa S; Kelly, Cathal K; Leahy, Austin L; Bouchier-Hayes, David J; Athanasiou, Thanos; Lee, Michael J; Department of Academic Radiology, Beaumont Hospital, Beaumont Road, Dublin 9, Ireland. (2009-09)
      The clinical importance of angiographically detected asymptomatic lower-limb stenoses and occlusions is unknown. This study aims to (i) assess the clinical outcome of asymptomatic lesions in the lower limb, (ii) identify predictors of clinical deterioration, and (iii) determine which asymptomatic lower-limb lesions should be treated at presentation.