• Bacteria, genetics and irritable bowel syndrome.

      Craig, Orla F; Quigley, Eamonn M M; University College Cork, Cork, Ireland. (2010-06)
      EVALUATION OF: Villani AC, Lemire M, Thabane M et al. Genetic risk factors for post-infectious irritable bowel syndrome following a waterborne outbreak of gastroenteritis. Gastroenterology 138, 1502-1513 (2010). While the pathogenesis of irritable bowel syndrome (IBS) remains to be fully defined, two clinical observations - the occurrence, de novo, of IBS following bacterial gastroenteritis and the history, commonly obtained from IBS patients, of other instances of the syndrome within their families - have instigated investigations, in IBS, of the potential roles, on the one hand, of the gut microbiota and the host response and, on the other hand, of genetic factors. The study reviewed here relates to both of these factors by studying genetic predisposition to postinfective IBS in a large population of individuals who were exposed to a multimicrobial enteric infection, which resulted in a severe outbreak of gastroenteritis and was followed by the development of IBS in over a third. In this detailed study, the investigators identified a number of genes that were linked significantly to the development of postinfectious-IBS in the Toll-like receptor 9, IL-6 and cadherin 1 regions. These genes play important roles in bacterial recognition, the inflammatory response and epithelial integrity, respectively, and provide considerable support for the hypothesis that links IBS onset to disturbances in the microbiota and the host response.
    • Bacteria: a new player in gastrointestinal motility disorders--infections, bacterial overgrowth, and probiotics.

      Quigley, Eamonn M M; Department of Medicine, Alimentary Pharmabiotic Centre, University College Cork, , Clinical Sciences Building, Cork University Hospital, Cork, Ireland., e.quigley@ucc.ie (2012-02-03)
      Irritable bowel syndrome (IBS) may result from a dysfunctional interaction between the indigenous flora and the intestinal mucosa, which in turn leads to immune activation in the colonic mucosa. Some propose that bacterial overgrowth is a common causative factor in the pathogenesis of symptoms in IBS; others point to evidence suggesting that the cause stems from more subtle qualitative changes in the colonic flora. Bacterial overgrowth will probably prove not to be a major factor in what will eventually be defined as IBS. Nevertheless, short-term therapy with either antibiotics or probiotics seems to reduce symptoms among IBS patients. However, in the long term, safety issues will favor the probiotic approach; results of long-term studies with these agents are eagerly awaited.
    • Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system.

      Killeen, S D; Wang, J H; Andrews, E J; Redmond, H P; Department of Academic Surgery, Cork University Hospital and University College Cork, Cork, Ireland. sdfkilleen@eircom.net (2009-05-19)
      Perioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.
    • Bacterial lipoprotein delays apoptosis in human neutrophils through inhibition of caspase-3 activity: regulatory roles for CD14 and TLR-2.

      Power, Colm P; Wang, Jiang H; Manning, Brian; Kell, Malcolm R; Aherne, Noel J; Wu, Qiong D; Redmond, H Paul; Department of Academic Surgery, National University of Ireland, Cork University, Hospital. cjppower@yahoo.com (2012-02-03)
      The human sepsis syndrome resulting from bacterial infection continues to account for a significant proportion of hospital mortality. Neutralizing strategies aimed at individual bacterial wall products (such as LPS) have enjoyed limited success in this arena. Bacterial lipoprotein (BLP) is a major constituent of the wall of diverse bacterial forms and profoundly influences cellular function in vivo and in vitro, and has been implicated in the etiology of human sepsis. Delayed polymorphonuclear cell (PMN) apoptosis is a characteristic feature of human sepsis arising from Gram-negative or Gram-positive bacterial infection. Bacterial wall product ligation and subsequent receptor-mediated events upstream of caspase inhibition in neutrophils remain incompletely understood. BLP has been shown to exert its cellular effects primarily through TLR-2, and it is now widely accepted that lateral associations with the TLRs represent the means by which CD14 communicates intracellular messages. In this study, we demonstrate that BLP inhibits neutrophil mitochondrial membrane depolarization with a subsequent reduction in caspase-3 processing, ultimately leading to a significant delay in PMN apoptosis. Pretreatment of PMNs with an anti-TLR-2 mAb or anti-CD14 mAb prevented BLP from delaying PMN apoptosis to such a marked degree. Combination blockade using both mAbs completely prevented the effects of BLP (in 1 and 10 ng/ml concentrations) on PMN apoptosis. At higher concentrations of BLP, the antiapoptotic effects were observed, but were not as pronounced. Our findings therefore provide the first evidence of a crucial role for both CD14 and TLR-2 in delayed PMN apoptosis arising from bacterial infection.
    • Bacterial lipoprotein-induced self-tolerance and cross-tolerance to LPS are associated with reduced IRAK-1 expression and MyD88-IRAK complex formation.

      Li, Chong Hui; Wang, Jiang Huai; Redmond, H Paul; Department of Academic Surgery, National University of Ireland (NUI)/University, College Cork, Cork University Hospital, Cork, Ireland. (2012-02-03)
      Tolerance to bacterial cell-wall components may represent an essential regulatory mechanism during bacterial infection. We have demonstrated previously that the inhibition of nuclear factor (NF)-kappaB and mitogen-activated protein kinase activation was present in bacterial lipoprotein (BLP) self-tolerance and its cross-tolerance to lipopolysaccharide (LPS). In this study, the effect of BLP-induced tolerance on the myeloid differentiation factor 88 (MyD88)-dependent upstream signaling pathway for NF-kappaB activation in vitro was examined further. When compared with nontolerant human monocytic THP-1 cells, BLP-tolerant cells had a significant reduction in tumor necrosis factor alpha (TNF-alpha) production in response to a high-dose BLP (86+/-12 vs. 6042+/-245 ng/ml, P < 0.01) or LPS (341+/-36 vs. 7882+/-318 ng/ml, P < 0.01) stimulation. The expression of Toll-like receptor 2 (TLR2) protein was down-regulated in BLP-tolerant cells, whereas no significant differences in TLR4, MyD88, interleukin-1 receptor-associated kinase 4 (IRAK-4), and TNF receptor-associated factor 6 expression were observed between nontolerant and BLP-tolerant cells, as confirmed by Western blot analysis. The IRAK-1 protein was reduced markedly in BLP-tolerant cells, although IRAK-1 mRNA expression remained unchanged as revealed by real-time reverse transcriptase-polymerase chain reaction analysis. Furthermore, decreased MyD88-IRAK immunocomplex formation, as demonstrated by immunoprecipitation, was observed in BLP-tolerant cells following a second BLP or LPS stimulation. BLP pretreatment also resulted in a marked inhibition in total and phosphorylated inhibitor of kappaB-alpha (IkappaB-alpha) expression, which was not up-regulated by subsequent BLP or LPS stimulation. These results demonstrate that in addition to the down-regulation of TLR2 expression, BLP tolerance is associated with a reduction in IRAK-1 expression, MyD88-IRAK association, and IkappaB-alpha phosphorylation. These findings further elucidate the molecular mechanisms underlying bacterial peptide tolerance.
    • Bacterial lipoprotein-induced tolerance is reversed by overexpression of IRAK-1.

      Li, Chong Hui; Liu, Jinghua; An, Mingbang; Redmond, H Paul; Wang, Jiang Huai; Department of Academic Surgery, University College Cork (UCC)/National University of Ireland (NUI), Cork University Hospital, Cork, Ireland. (2012-03)
      Tolerance to bacterial cell wall components including bacterial lipoprotein (BLP) represents an essential regulatory mechanism during bacterial infection. Reduced Toll-like receptor 2 (TLR2) and IL-1 receptor-associated kinase 1 (IRAK-1) expression is a characteristic of the downregulated TLR signaling pathway observed in BLP-tolerised cells. In this study, we attempted to clarify whether TLR2 and/or IRAK-1 are the key molecules responsible for BLP-induced tolerance. Transfection of HEK293 cells and THP-1 cells with the plasmid encoding TLR2 affected neither BLP tolerisation-induced NF-κB deactivation nor BLP tolerisation-attenuated pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) production, indicating that BLP tolerance develops despite overexpression of TLR2 in these cells. In contrast, overexpression of IRAK-1 reversed BLP-induced tolerance, as transfection of IRAK-1 expressing vector resulted in a dose-dependent NF-κB activation and TNF-α release in BLP-tolerised cells. Furthermore, BLP-tolerised cells exhibited markedly repressed NF-κB p65 phosphorylation and impaired binding of p65 to several pro-inflammatory cytokine gene promoters including TNF-α and interleukin-6 (IL-6). Overexpression of IRAK-1 restored the nuclear transactivation of p65 at both TNF-α and IL-6 promoters. These results indicate a crucial role for IRAK-1 in BLP-induced tolerance, and suggest IRAK-1 as a potential target for manipulation of the TLR-mediated inflammatory response during microbial sepsis.
    • Bacterial wall products induce downregulation of vascular endothelial growth factor receptors on endothelial cells via a CD14-dependent mechanism: implications for surgical wound healing.

      Power, C; Wang, J H; Sookhai, S; Street, J T; Redmond, H P; Department of Academic Surgery, Cork University Hospital, Wilton, Cork, Ireland. , cjppower@yahoo.com (2012-02-03)
      INTRODUCTION: Vascular endothelial growth factor (VEGF) is a potent mitogenic cytokine which has been identified as the principal polypeptide growth factor influencing endothelial cell (EC) migration and proliferation. Ordered progression of these two processes is an absolute prerequisite for initiating and maintaining the proliferative phase of wound healing. The response of ECs to circulating VEGF is determined by, and directly proportional to, the functional expression of VEGF receptors (KDR/Flt-1) on the EC surface membrane. Systemic sepsis and wound contamination due to bacterial infection are associated with significant retardation of the proliferative phase of wound repair. The effects of the Gram-negative bacterial wall components lipopolysaccharide (LPS) and bacterial lipoprotein (BLP) on VEGF receptor function and expression are unknown and may represent an important biological mechanism predisposing to delayed wound healing in the presence of localized or systemic sepsis. MATERIALS AND METHODS: We designed a series of in vitro experiments investigating this phenomenon and its potential implications for infective wound repair. VEGF receptor density on ECs in the presence of LPS and BLP was assessed using flow cytometry. These parameters were assessed in hypoxic conditions as well as in normoxia. The contribution of CD14 was evaluated using recombinant human (rh) CD14. EC proliferation in response to VEGF was quantified in the presence and absence of LPS and BLP. RESULTS: Flow cytometric analysis revealed that LPS and BLP have profoundly repressive effects on VEGF receptor density in normoxic and, more pertinently, hypoxic conditions. The observed downregulation of constitutive and inducible VEGF receptor expression on ECs was not due to any directly cytotoxic effect of LPS and BLP on ECs, as measured by cell viability and apoptosis assays. We identified a pivotal role for soluble/serum CD14, a highly specific bacterial wall product receptor, in mediating these effects. The decreased VEGF receptor density on ECs accruing from the presence of bacterial wall products resulted in EC hyporesponsiveness to rhVEGF and significant abolition of VEGF-directed EC proliferation. CONCLUSION: These findings suggest that the well-recognized relationship between bacterial sepsis and attenuated wound healing may be due, in part, to the directly suppressive effects of bacterial wall components on EC VEGF receptor expression and, consequently, EC proliferation.
    • Balloon dacryocystoplasty study in the management of adult epiphora.

      Fenton, S; Cleary, P E; Horan, E; Murray, A; Ho, S L; Ryder, D; O'Connor, G; Department of Ophthalmology, Cork University Hospital, Ireland. (2012-02-03)
      PURPOSE: To determine the efficacy of dacryocystoplasty with balloon dilation in the treatment of acquired obstruction of the nasolacrimal system in adults. METHODS: Balloon dacryocystoplasty was performed in 52 eyes of 42 patients under general anaesthetic. A Teflon-coated guidewire was introduced through the canaliculus and manipulated through the nasolacrimal system and out of the nasal aperture. A 4 mm wide 3 cm coronary angioplasty balloon catheter was threaded over the guidewire in a retrograde fashion and dilated at the site of obstruction. RESULTS: There was complete obstruction in 30% of cases and partial obstruction in 70%. The most common site of obstruction was the nasolacrimal duct. The procedure was technically successful in 94% of cases. The overall re-obstruction rate was 29% within 1 year of the procedure. There was an anatomical failure rate of 17% for partial obstruction and 69% for complete obstruction within 1 year. CONCLUSIONS: Balloon dacryocystoplasty has a high recurrence rate. There may be a limited role for this procedure in partial obstructions. Further refinements of the procedure are necessary before it can be offered as a comparable alternative to a standard surgical dacryocystorhinostomy.
    • Barrett's esophagus: clinical features, obesity, and imaging.

      Quigley, Eamonn M M; Jacobson, Brian C; Lenglinger, Johannes; Rubenstein, Joel H; El-Serag, Hashem; Cicala, Michele; McCallum, Richard W; Levine, Marc S; Gore, Richard M; Alimentary Pharmabiotic Centre, Department of Medicine, Clinical Sciences Building, Cork University Hospital, Cork, Ireland. (Wiley-Blackwell, 2011-09)
      The following includes commentaries on clinical features and imaging of Barrett's esophagus (BE); the clinical factors that influence the development of BE; the influence of body fat distribution and central obesity; the role of adipocytokines and proinflammatory markers in carcinogenesis; the role of body mass index (BMI) in healing of Barrett's epithelium; the role of surgery in prevention of carcinogenesis in BE; the importance of double-contrast esophagography and cross-sectional images of the esophagus; and the value of positron emission tomography/computed tomography.
    • The Barthel Index: comparing inter-rater reliability between nurses and doctors in an older adult rehabilitation unit.

      Hartigan, Irene; O'Mahony, Denis; Catherine McAuley School of Nursing and Midwifery, Brookfield Health Science Complex, University College Cork, Ireland. i.hartigan@ucc.ie (Elsevier, 2011-02)
      To ensure accuracy in recording the Barthel Index (BI) in older people, it is essential to determine who is best placed to administer the index. The aim of this study was to compare doctors' and nurses' reliability in scoring the BI.
    • BCG protects toddlers during a tuberculosis outbreak.

      Gaensbauer, J T; Vandaleur, M; O'Neil, M; Altaf, A; Ní Chróinín, M; Division of Paediatrics, Cork University Hospital, Wilton Road, Wilton, Cork, Ireland. jgaens@u.washington.edu (2009-05)
      In 2007, an outbreak of tuberculosis occurred in a toddler population attending two child care centres in Cork, Ireland. Of 268 children exposed, 18 were eventually diagnosed with active tuberculosis. We present the initial clinical and radiographic characteristics of the active disease group. Mantoux testing was positive in only 66% of cases. All cases were either pulmonary or involved hilar adenopathy on chest radiograph; there were no cases of disseminated disease or meningitis. 24% of the exposed children had been previously vaccinated with BCG, and no case of active disease was found in this group (p = 0.016), suggesting a profound protective effect of BCG in this population. Our experience provides evidence supporting a protective effect of BCG against pulmonary disease in young children.
    • Bcl-x(L) expression in vivo in rheumatoid synovium.

      Busteed, S; Bennett, M W; Molloy, C; Houston, A; Stone, M A; Shanahan, F; Molloy, M G; O'Connell, J; Department of Medicine, Cork University Hospital, National University of Ireland,, Wilton, Cork, Ireland. sandra_busteed@hotmail.com (2012-02-03)
      To examine the expression of the apoptosis regulatory protein, Bcl-x(L), in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunohistochemistry for Bcl-x(L) was carried out on synovial samples from patients with RA and OA. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis were performed to qualitatively examine the expression of Bcl-x(L). Bcl-x(L) expression was detected in the lining, endothelium and inflammatory cells of both RA (n=20) and OA (n=10) samples. However, there was significantly more expression in the lining of RA synovium compared to OA (77 vs 61%, p<0.05). Many of the positive cells in the RA subsynovium were noted to be plasma cells. There was a significant correlation between Bcl-x(L) expression and the number of inflammatory cells in the subsynovium of RA and OA patients (r (s)=0.376, p<0.05, n=30). Age and disease duration did not correlate with Bcl-x(L) expression in rheumatoid patients. Bcl-x(L) may play a role in the extended survival of synoviocytes and inflammatory cells in rheumatoid synovium.
    • Behaviour of spectral entropy, spectral edge frequency 90%, and alpha and beta power parameters during low-dose propofol infusion.

      Mahon, P; Greene, B R; Greene, C; Boylan, G B; Shorten, G D; Department of Anaesthesia and Intensive Care Medicine, Cork University Hospital, , Cork, Ireland. rsimahon@hotmail.com (2012-02-03)
      BACKGROUND: In this study we analyse the behaviour, potential clinical application and optimal cortical sampling location of the spectral parameters: (i) relative alpha and beta power; (ii) spectral edge frequency 90%; and (iii) spectral entropy as monitors of moderate propofol-induced sedation. METHODS: Multi-channel EEG recorded from 12 ASA 1 (American Society of Anesthesiologists physical status 1) patients during low-dose, target effect-site controlled propofol infusion was used for this analysis. The initial target effect-site concentration was 0.5 microg ml(-1) and increased at 4 min intervals in increments of 0.5 to 2 microg ml(-1). EEG parameters were calculated for 2 s epochs in the frequency ranges 0.5-32 and 0.5-47 Hz. All parameters were calculated in the channels: P4-O2, P3-O1, F4-C4, F3-C3, F3-F4, and Fp1-Fp2. Sedation was assessed clinically using the OAA/S (observer's assessment of alertness/sedation) scale. RESULTS: Relative beta power and spectral entropy increased with increasing propofol effect-site concentration in both the 0.5-47 Hz [F(18, 90) = 3.455, P<0.05 and F(18, 90) = 3.33, P<0.05, respectively] and 0.5-32 Hz frequency range. This effect was significant in each individual channel (P<0.05). No effect was seen of increasing effect-site concentration on relative power in the alpha band. Averaged across all channels, spectral entropy did not outperform relative beta power in either the 0.5-32 Hz [Pk=0.79 vs 0.814 (P>0.05)] or 0.5-47 Hz range [Pk=0.81 vs 0.82 (P>0.05)]. The best performing indicator in any single channel was spectral entropy in the frequency range 0.5-47 Hz in the frontal channel F3-F4 (Pk=0.85). CONCLUSIONS: Relative beta power and spectral entropy when considered over the propofol effect-site range studied here increase in value, and correlate well with clinical assessment of sedation.
    • The benefits of a laparoscopic approach in ileal pouch anal anastomosis formation: a single institutional retrospective case-matched experience.

      Kelly, J; Condon, E T; Redmond, H P; Kirwan, W O; Department of Colorectal Surgery, Cork University Hospital, Wilton, Cork, Ireland. justinjoshkelly@gmail.com (2010-06)
      A laparoscopic approach to ileoanal pouch formation is novel. By using prospectively gathered data, laparoscopic and open restorative proctocolectomy procedures in mucosal ulcerative colitis (UC) and familial adenomatous polyposis (FAP) patients were compared using a case-matched design.
    • The benefits of an interactive, individualized online patient pathway for patients undergoing minimally invasive radioguided parathyroidectomy: a prospective, double-blinded, randomized clinical trial.

      Neary, Peter M; Sung, Robert; Corrigan, Mark; O'Donovan, Maurice; Cahill, Ronan A; Redmond, H Paul; Cork University Hospital, Cork, Ireland. peterneary@hotmail.com (2010-09)
      This study determined the usefulness of an interactive, individualized online patient pathway to patients undergoing elective operation for nonmalignant disease.
    • Bifidobacterium bifidum MIMBb75 in irritable bowel syndrome.

      Quigley, E M M (Blackwell Publishing Ltd., 2011-07)
    • Bilateral brachial neuropathy and acute aortic dissection due to giant cell arteritis.

      Saidha, S; Mok, T H; Butler, M; Keohane, C; Harrington, H (2009-08)
    • Bilateral inferior vena cava filter insertion in a patient with duplication of the infrarenal vena cava.

      Leong, S; Oisin, F; Barry, J E; Maher, M M; Bogue, C O; Department of Radiology, Cork University Hospital, Wilton, Cork, Ireland, leong81@gmail.com. (2010-06-19)
      BACKGROUND: Inferior vena cava (IVC) filter insertion is a commonly performed procedure for indications such as recurrent pulmonary emboli or contraindication to anticoagulation. Symptomatic duplication of the IVC is exceedingly rare with only a handful of cases being described in the literature. AIM: We report an unusual case of a patient with symptomatic duplication of the IVC. RESULT: A 53-year-old woman presented at our hospital for resection of a cerebral metastasis from a non-small cell lung cancer following a recent diagnosis of bilateral lower limb deep venous thrombosis. This required perioperative reversal of anticoagulation and IVC filter insertion. Conventional venography performed during filter insertion documented the existence of a duplicated IVC. CONCLUSION: We present a case of a symptomatic duplication of the IVC requiring filter insertion. We review the developmental anatomy of the IVC along with the diagnostic findings and management strategies available.
    • Bilateral malignant ovarian haemangiopericytoma.

      Wong, V V; O'Brien, O; De Tavernier, M; Department of Gynaecology, Cork University Hospital, Wilton, Cork, Republic of Ireland. vuivunwong@yahoo.com (2011)
    • Bilateral spontaneous rupture of flexor digitorum profundus tendons.

      O'Sullivan, S T; Reardon, C M; O'Shaughnessy, M; Condon, K C; Department of Plastic Surgery, Cork University Hospital, Wilton, Ireland. (2012-02-03)
      Spontaneous tendon rupture is an unusual condition usually associated with underlying disease processes such as rheumatoid arthritis, chronic renal failure or bony abnormalities of the hand. We report a case of spontaneous, non-concurrent bilateral rupture of flexor profundus tendons in an otherwise healthy individual. Treatment was successful and consisted of a two-stage reconstruction of the ruptured tendon.