• N-cadherin is overexpressed in Crohn's stricture fibroblasts and promotes intestinal fibroblast migration.

      Burke, John P; Cunningham, Michael F; Sweeney, Catherine; Docherty, Neil G; O'Connell, P Ronan; Department of Surgery, St. Vincent's University Hospital, Dublin, Ireland. (2012-02-01)
      BACKGROUND: Intestinal fibroblasts mediate stricture formation in Crohn's disease (CD). Transforming growth factor-beta (TGF-beta) is important in fibroblast activation, while cell attachment and migration is regulated by the adhesion molecule N-cadherin. The aim of this study was to investigate the expression and function of N-cadherin in intestinal fibroblasts in patients with fibrostenosing CD. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies from patients undergoing resection for terminal ileal fibrostenosing CD (n = 14) or controls patients (n = 8). N-cadherin expression was assessed using Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Fibroblasts were stimulated with TGF-beta and selective pathway inhibitors Y27632, PD98050, and LY294002 were used to examine the Rho/ROCK, ERK-1/2, and Akt signaling pathways, respectively. Cell migration was assessed using a scratch wound assay. N-cadherin was selectively overexpressed using a plasmid. RESULTS: Fibroblasts from fibrostenosing CD express increased constitutive N-cadherin mRNA and protein and exhibit enhanced basal cell migration relative to those from directly adjacent normal bowel. Control fibroblasts treated with TGF-beta induced N-cadherin in a dose-dependent manner which was inhibited by Rho/ROCK and Akt pathway modulation. Control fibroblasts exhibited enhanced cell migration in response to treatment with TGF-beta or transfection with an N-cadherin plasmid. CONCLUSIONS: Fibroblasts from strictures in CD express increased constitutive N-cadherin and exhibit enhanced basal cell migration. TGF-beta is a potent inducer of N-cadherin in intestinal fibroblasts resulting in enhanced cell migration. The TGF-beta-mediated induction of N-cadherin may potentiate Crohn's stricture formation.
    • Nasal pillows as an alternative interface in patients with obstructive sleep apnoea syndrome initiating continuous positive airway pressure therapy.

      Ryan, Silke; Garvey, John F; Swan, Valerie; Behan, Renata; McNicholas, Walter T; Sleep Research Laboratory, St Vincent's University Hospital, Dublin, Ireland. (2012-02-01)
      Side-effects directly due to the nasal mask are common in patients with obstructive sleep apnoea syndrome (OSAS) commencing continuous positive airway pressure (CPAP). Recently, nasal pillows have been designed to overcome these issues. Limited evidence exists of the benefits and effectiveness of these devices. Twenty-one patients (19 male, 49+/-10years) with the established diagnosis of OSAS [apnoea/hypopnoea index (AHI): 52+/-22] and who had a successful CPAP titration were commenced on CPAP therapy (10+/-2cmH2O), and randomized to 4weeks of a nasal pillow (P) and a standard nasal mask (M) in a crossover design. Outcome measures were objective compliance, AHI, quality of life, Epworth Sleepiness Score (ESS) and CPAP side-effects. There was no difference in compliance (M versus P: 5.1+/-1.9h versus 5.0+/-1.7h; P=0.701) and AHI (2.6+/-2.7 versus 3.0+/-2.9; P=0.509). Quality of life and ESS improved with CPAP, but there was no difference in the extent of improvement between both devices. Usage of nasal pillows resulted in less reported pressure on the face and more subjects found the nasal pillow the more comfortable device. However, there was no clear overall preference for either device at the end of the study (mask=57%, pillow=43%; P=0.513). The applied CPAP pressure did not correlate with compliance, AHI and ESS. Furthermore, no differences in outcome parameters were noted comparing groups with CPAP pressure <10 and >/=10cm H(2) O. Nasal pillows are equally effective in CPAP therapy, but do not generally lead to improved compliance.
    • Natalizumab therapy of multiple sclerosis.

      Hutchinson, Michael; Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland., mhutchin@iol.ie (2012-02-01)
      Multiple sclerosis (MS) is the commonest disabling neurological disease of young and middle-aged adults affecting 1 million persons world wide. The illness begins with a relapsing-remitting MS course in 85%-90% of patients; the other 10%-15% have a primary progressive onset MS. Our current understanding is that MS is an autoimmune disorder with an inflammatory T-cell attack on myelin or some component of the oligodendrocyte--myelin structure. Relapses of disease activity result in plaques of demyelination with destruction of myelin and, to a lesser, extent axons. Lymphocytes within the central nervous system tissue recruit more cells leading to an inflammatory cascade that causes myelin damage, axonal disruption, and neuronal death. If the plaque occurs in a vocal area of the central nervous system then symptoms relating to that area result. However, magnetic resonance imaging shows that approximately 10 times more lesions occur in asymptomatic areas of the brain. Recovery from an initial relapse may appear relatively complete but persistent inflammation results in axonal injury and residual disability results. With time and accumulated lesion load, secondary degeneration of denuded axons results in the phase of secondary progressive MS usually 15-20 years after onset.
    • A national survey of publicly funded chronic pain management services in Ireland.

      Purcell, Andrew; Channappa, Keshava; Moore, David; Harmon, Dominic (2021-06-10)
      Background: Chronic pain management services have historically been under-resourced in Ireland. There is no agreed model of care for chronic pain management services in Ireland. Previous studies have assessed the extent of services in Ireland without examining waiting times for access to services. Aims: This study aimed to quantify the extent of, geographical distribution of and waiting times for access to publicly funded chronic pain management services in Ireland. Methods: Using the British Pain Society's Core Standards for Pain Management Services in the UK (2015) and International Association for the Study of Pain (IASP) recommendations, a questionnaire was devised. Publically funded departments in Ireland were contacted and questionnaires completed. Waiting list data was publicly available and obtained from the National Treatment Purchase Fund website. Results: There was a 100% response rate. Sixteen publicly funded chronic pain management services were identified. There are 27 chronic pain management consultants (16.6 whole time equivalents (WTE)) practicing chronic pain management, amounting to 0.55 specialists (0.34 WTEs)/100,000 of the population. There are 21 WTE for non-consultant hospital doctors (NCHDs), 26.5 WTEs for nursing, 8 WTEs for physiotherapy and 6.2 WTEs for psychology, nationally. A percentage of 93.75% of departments (n = 15) provide interventional therapies, 37.5% (n = 6) provide advanced neuromodulation and 43.75% (n = 7) are managing intrathecal pump therapies. There are five pain management programmes nationally. As of January 2020, ~ 25% patients on waiting lists for outpatient appointments were waiting > 18 months, with ~ 17% patients on waiting lists for interventional treatments waiting > 12 months. Conclusions: Shortage of multidisciplinary staff is of particular concern for Irish services. Patient access is limited as evidenced by significant waiting lists. In order to improve access to care and bring services in line with international recommendations, increased resources are needed.
    • Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone.

      Mak, George J; Ledwidge, Mark T; Watson, Chris J; Phelan, Dermot M; Dawkins, Ian R; Murphy, Niamh F; Patle, Anil K; Baugh, John A; McDonald, Kenneth M; St. Vincent's University Hospital, Dublin, Ireland. (2012-02-01)
      OBJECTIVES: This study was designed to evaluate the impact of eplerenone on collagen turnover in preserved systolic function heart failure (HFPSF). BACKGROUND: Despite growing interest in abnormal collagen metabolism as a feature of HFPSF with diastolic dysfunction, the natural history of markers of collagen turnover and the impact of selective aldosterone antagonism on this natural history remains unknown. METHODS: We evaluated 44 patients with HFPSF, randomly assigned to control (n = 20) or eplerenone 25 mg daily (n = 24) for 6 months, increased to 50 mg daily from 6 to 12 months. Serum markers of collagen turnover and inflammation were analyzed at baseline and at 6 and 12 months and included pro-collagen type-I and -III aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha. Doppler-echocardiographic assessment of diastolic filling indexes and tissue Doppler analyses were also obtained. RESULTS: The mean age of the patients was 80 +/- 7.8 years; 46% were male; 64% were receiving an angiotensin-converting enzyme inhibitor, 34% an angiotensin-II receptor blocker, and 68% were receiving beta-blocker therapy. Pro-collagen type-III and -I aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha increased with time in the control group. Eplerenone treatment had no significant impact on any biomarker at 6 months but attenuated the increase in pro-collagen type-III aminoterminal peptide at 12 months (p = 0.006). Eplerenone therapy was associated with modest effects on diastolic function without any impact on clinical variables or brain natriuretic peptide. CONCLUSIONS: This study demonstrates progressive increases in markers of collagen turnover and inflammation in HFPSF with diastolic dysfunction. Despite high background utilization of renin-angiotensin-aldosterone modulators, eplerenone therapy prevents a progressive increase in pro-collagen type-III aminoterminal peptide and may have a role in management of this disease. (The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure; NCT00505336).
    • Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke.

      O'Shea, Donal; Cawood, Tom J; O'Farrelly, Cliona; Lynch, Lydia; Department of Endocrinology, St. Vincent's University Hospital, Dublin, Ireland. (2012-02-01)
      BACKGROUND: Obese individuals who smoke have a 14 year reduction in life expectancy. Both obesity and smoking are independently associated with increased risk of malignancy. Natural killer cells (NK) are critical mediators of anti-tumour immunity and are compromised in obese patients and smokers. We examined whether NK cell function was differentially affected by cigarette smoke in obese and lean subjects. METHODOLOGY AND PRINCIPAL FINDINGS: Clinical data and blood were collected from 40 severely obese subjects (BMI>40 kg/m(2)) and 20 lean healthy subjects. NK cell levels and function were assessed using flow cytometry and cytotoxicity assays. The effect of cigarette smoke on NK cell ability to kill K562 tumour cells was assessed in the presence or absence of the adipokines leptin and adiponectin. NK cell levels were significantly decreased in obese subjects compared to lean controls (7.6 vs 16.6%, p = 0.0008). NK function was also significantly compromised in obese patients (30% +/- 13% vs 42% +/-12%, p = 0.04). Cigarette smoke inhibited NK cell ability to kill tumour cell lines (p<0.0001). NK cells from obese subjects were even more susceptible to the inhibitory effects of smoke compared to lean subjects (33% vs 28%, p = 0.01). Cigarette smoke prevented NK cell activation, as well as perforin and interferon-gamma secretion upon tumour challenge. Adiponectin but not leptin partially reversed the effects of smoke on NK cell function in both obese (p = 0.002) and lean controls (p = 0.01). CONCLUSIONS/SIGNIFICANCE: Obese subjects have impaired NK cell activity that is more susceptible to the detrimental effects of cigarette smoke compared to lean subjects. This may play a role in the increase of cancer and infection seen in this population. Adiponectin is capable of restoring NK cell activity and may have therapeutic potential for immunity in obese subjects and smokers.
    • Natural killer cells in psoriasis.

      Tobin, A M; Lynch, L; Kirby, B; O'Farrelly, C; Department of Dermatology, St Vincent's University Hospital, Dublin, Ireland., tobin.annemarie@gmail.com (2012-02-01)
      Psoriasis is one of the most common immune-mediated disorders. There is evidence that it is mediated by Th1 and, more recently, Th17 cells. The cytokine pattern, particularly the dominance of TNF-alpha, implicates the innate immune system in psoriasis pathogenesis. Of the many components of the innate immune system known to be involved in psoriatic lesions, natural killer and natural killer T cells appear to have a unique role. We review the evidence supporting a role for natural killer cells in psoriasis.
    • Neisseria meningitidis as a Cause of Septic Arthritis: An Unusual Case of Periprosthetic Joint Infection.

      Mc Carthy, A; Broderick, J M; Molloy, A P (2020-03-10)
      One of the most feared complications after arthroplasty is infection due to its significant impact on patient morbidity. Infection may transfer to the joint at the time of surgery or be seeded, haematologically, to the prosthetic joint from another infection source. In this case, a 72-year-old female presented with symptoms of septic arthritis seven years after her original arthroplasty surgery. At presentation, she denied trauma and any comorbidity which would predispose her to infection. Culturing of samples taken revealed the patient was infected with Neisseria meningitidis, and the patient underwent a DAIR procedure. She continued postoperative long-term antimicrobial therapy with resolution of her infection. Follow-up at one year showed complete resolution of the patient's illness with a return to premorbid baseline. To our knowledge, this is the third reported case of septic arthritis caused by Neisseria meningitidis in a prosthetic joint in the literature.
    • A nodal positivity constant: new perspectives in lymph node evaluation and colorectal cancer.

      Hogan, Niamh M; Winter, Desmond C; Institute for Clinical Outcomes Research and Education (iCORE), St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. niamhogan@gmail.com (2013-04)
      To date, associations between the number of lymph nodes evaluated, staging, and survival have been examined in the context of large population-based studies conducted by a small number of investigators. Therefore, although high-quality data are available, perspective is lacking.
    • Noncardiac findings on cardiac CT part I: Pros and cons.

      Killeen, Ronan P; Dodd, Jonathan D; Cury, Ricardo C; Department of Radiology, St. Vincent's University Hospital, Dublin 4, Ireland. (2012-02-01)
      Cardiac computed tomography (CT) has evolved into an effective imaging technique for the evaluation of coronary artery disease in selected patients. Two distinct advantages over other noninvasive imaging modalities include its ability to evaluate directly the coronary arteries and to provide an opportunity to evaluate extracardiac structures, such as the lungs and mediastinum. Some centers reconstruct a small field of view (FOV) cropped around the heart, but a full FOV (from skin to skin in the irradiated area) is obtainable in the raw data of every scan so that clinically relevant noncardiac findings are identifiable. Debate in the scientific community has centered on the necessity for this large FOV evaluation. A review of noncardiac structures provides the opportunity to make alternative diagnoses that may account for the patient's presentation or to detect important but clinically silent problems such as lung cancer. Critics argue that the yield of biopsy-proven cancers is low and that the follow-up of incidental noncardiac findings is expensive, resulting in increased radiation exposure and possibly unnecessary further testing. In this two-part review we outline the issues surrounding the concept of the noncardiac read looking for noncardiac findings on cardiac CT. Part I focuses on the pros and cons of the practice of identifying noncardiac findings on cardiac CT.
    • Noncardiac findings on cardiac CT. Part II: spectrum of imaging findings.

      Killeen, Ronan P; Cury, Ricardo C; McErlean, Aoife; Dodd, Jonathan D; Department of Radiology, St. Vincent's University Hospital, Elm Park, Dublin 4,, Ireland. (2012-02-01)
      Cardiac computed tomography (CT) has evolved into an effective imaging technique for the evaluation of coronary artery disease in selected patients. Two distinct advantages over other noninvasive cardiac imaging methods include its ability to directly evaluate the coronary arteries and to provide a unique opportunity to evaluate for alternative diagnoses by assessing the extracardiac structures, such as the lungs and mediastinum, particularly in patients presenting with the chief symptom of acute chest pain. Some centers reconstruct a small field of view (FOV) cropped around the heart but a full FOV (from skin to skin in the area irradiated) is obtainable in the raw data of every scan so that clinically relevant noncardiac findings are identifiable. Debate in the scientific community has centered on the necessity for this large FOV. A review of noncardiac structures provides the opportunity to make alternative diagnoses that may account for the patient's presentation or to detect important but clinically silent problems such as lung cancer. Critics argue that the yield of biopsy-proven cancers is low and that the follow-up of incidental noncardiac findings is expensive, resulting in increased radiation exposure and possibly unnecessary further testing. In this 2-part review we outline the issues surrounding the concept of the noncardiac read, looking for noncardiac findings on cardiac CT. Part I focused on the pros and cons for and against the practice of identifying noncardiac findings on cardiac CT. Part II illustrates the imaging spectrum of cardiac CT appearances of benign and malignant noncardiac pathology.
    • Nonmelanoma skin cancer risk awareness in azathioprine-treated myasthenia gravis patients.

      McGurgan, Iain J; McGuigan, Christopher (Wiley, 2015-10)
      Increased rates of NMSC (nonmelanoma skin cancer) have recently been reported in people with MG (myasthenia gravis) receiving azathioprine treatment. Guidelines on azathioprine for patients with dermatological and gastrointestinal disorders stress the importance of NMSC risk awareness and prevention. The aim of this study is to assess whether MG patients are being informed of this risk.
    • Nuclear oxidative damage correlates with poor survival in colorectal cancer.

      Sheridan, J; Wang, L-M; Tosetto, M; Sheahan, K; Hyland, J; Fennelly, D; O'Donoghue, D; Mulcahy, H; O'Sullivan, J; Centre for Colorectal Disease, St Vincent's University Hospital, Elm Park Dublin , 4, Republic of Ireland. (2012-02-01)
      Oxidative DNA damage results from DNA adducts such as 8-oxo-7, 8 dihydro-2'-deoxyguanosine (8-oxo-dG), which is a pro-mutagenic lesion. No known association between 8-oxo-dG, disease progression and survival exists in colorectal cancer (CRC). We examined levels of 8-oxo-dG in sporadic CRC to determine its relationship with pathological stage and outcome. A total of 143 CRC patients and 105 non-cancer patients were studied. Nuclear and cytoplasmic 8-oxo-dG was assessed using immunohistochemistry. Double immunofluorescence using 8-oxo-dG and manganese superoxide dismutase (MnSOD) antibodies localised cytoplasmic 8-oxo-dG. Apoptosis was detected using TUNEL. Nuclear staining levels were similar in tumour tissue and matched normal mucosa in both epithelial (P=0.22) and stromal (P=0.85) cells. Epithelial cytoplasmic staining was greater in tumour tissue (P<0.001). Double immunofluorescence localised cytoplasmic 8-oxo-dG to mitochondria. Epithelial and stromal nuclear 8-oxo-dG decreased with local disease spread, but highest levels were found in distant disease (P<0.01). Survival was related to epithelial nuclear and stromal staining in normal mucosa (P<0.001) and tumour (P<0.01) but was unrelated to cytoplasmic staining. Normal control cells in tissue from cancer patients with high levels of 8-oxo-dG failed to undergo cell death. 8-oxo-dG may be an important biomarker of disease risk, progression and survival for CRC patients.
    • OAS1: a multiple sclerosis susceptibility gene that influences disease severity.

      O'Brien, M; Lonergan, R; Costelloe, L; O'Rourke, K; Fletcher, J M; Kinsella, K; Sweeney, C; Antonelli, G; Mills, K H; O'Farrelly, C; et al. (2012-02-01)
      BACKGROUND: Type 1 interferons upregulate oligoadenylate synthetase 1 (OAS1). A single nucleotide polymorphism (SNP) in exon 7 of OAS1 results in differential RNAseL enzyme activity, the A allele coding for a truncated form with low activity and the G conferring high activity. We hypothesized that OAS1 genotypes would influence both susceptibility to multiple sclerosis (MS) and disease activity with the AA genotype being overrepresented and the GG genotype underrepresented in relapsing-remitting MS (RRMS) with increased disease activity. METHODS: We examined OAS1 genotype distribution in 401 patients with MS, 394 healthy controls, and 178 patients with RRMS receiving interferon-beta (IFNbeta) assessed as 1) having no or minimal disease activity on IFNbeta, 2) having disease activity despite IFNbeta, and 3) 65 patients with RRMS with highly active disease. RESULTS: The OAS1 genotype distribution differed between patients with MS and controls (p = 0.000003), with lower frequency of GG homozygotes in patients with MS (6%) compared with controls (17%). In relation to disease severity, 34 (32%) patients with no or minimal disease activity on IFNbeta had the AA and 8 (8%) the GG genotype; of patients with disease activity despite IFNbeta, 27 (51%) were AA, while only 1 (2%) was GG (p = 0.03). Median time to first relapse on IFNbeta was 24 months in patients with RRMS with AA genotype and 33 months with AG or GG genotype (p = 0.04). The GG genotype was absent in 65 patients with highly active RRMS (p = 0.03). CONCLUSIONS: A functional OAS1 SNP, AA genotype, confers susceptibility to MS and the GG genotype may protect against increased disease activity.
    • Obesity in an ageing society: implications for health, physical function and health service utilisation

      Leahy, Siobhan; Nolan, Anne; O'Connell, Jean; Kenny, Rose Anne; The Irish Longitudinal Study on Ageing, Trinity College Dublin (TILDA, 2014-07)
      Obesity is a chronic disease defined by the World Health Organisation (WHO) as a condition of abnormal or excessive fat accumulation, to the extent that health may be impaired (1). This excess fat mass is thought to lead to a chronic, low grade inflammation which is associated with an increased risk of ill-health such as metabolic and cardiovascular disease, musculoskeletal problems, decreased physical function, and some cancers (2). Obesity prevalence has risen dramatically worldwide over the past 3-4 decades and is now considered a global epidemic (1, 3). Several societal factors have contributed to the rapid spread of obesity such as increasingly sedentary lifestyles and the widespread availability of energy dense foods in combination with a so-called ‘obesogenic environment’. However, the impact of obesity on health is complex, and differs, for example, according to age, sex and the trajectory of changes in body weight over time (
    • Objective assessment of surgical performance and its impact on a national selection programme of candidates for higher surgical training in plastic surgery.

      Carroll, Sean M; Kennedy, A M; Traynor, Oscar; Gallagher, Anthony G; St Vincent's University Hospital, Dublin 4, Ireland. smdc@indigo.ie (2012-02-01)
      OBJECTIVE: The objective of this study was to develop and validate a transparent, fair and objective assessment programme for the selection of surgical trainees into higher surgical training (HST) in plastic surgery in the Republic of Ireland. METHODS: Thirty-four individuals applied for HST in plastic surgery at the Royal College of Surgeons in Ireland (RCSI) in the academic years 2005-2006 and 2006-2007. Eighteen were short-listed for interview and further assessment. All applicants were required to report on their undergraduate educational performance and their postgraduate professional development. Short-listed applicants completed validated objective assessment simulations of surgical skills, an interview and assessment of their suitability for a career in surgery. RESULTS: When applicants' short-listing scores were combined with their interview scores and assessment of their suitability for a career in surgery, individuals who were selected for HST in plastic surgery performed significantly better than those who were not (P<0.002). However, when the assessment of technical skills scores were added the significance level of this difference increased further (P<0.0001) as did the statistical power of the difference to 99.9%, thus increasing the robustness of the selection package. CONCLUSION: The results from this study suggest that the assessment protocol we used to select individuals for HST in plastic surgery reliably and statistically significantly discriminated between the performances of candidates.
    • Obstructive sleep apnea and inflammation.

      McNicholas, Walter T; Sleep Research Laboratory, St. Vincent's University Hospital, Dublin, Ireland., walter.mcnicholas@ucd.ie (2012-02-01)
      The pathogenesis of cardiovascular complications in obstructive sleep apnea syndrome (OSAS) is not fully understood but is likely multifactorial in origin. Inflammatory processes play an important role in the pathogenesis of atherosclerosis, and circulating levels of several markers of inflammation have been associated with future cardiovascular risk. These include cell adhesion molecules such as intercellular adhesion molecule-1 and selectins, cytokines such as tumour necrosis factor alpha and interleukin 6, chemokines such as interleukin 8, and C-reactive protein. There is also increasing evidence that inflammatory processes play an important role in the cardiovascular pathophysiology of OSAS and many of the inflammatory markers associated with cardiovascular risk have been reported as elevated in patients with OSAS. Furthermore, animal and cell culture studies have demonstrated preferential activation of inflammatory pathways by intermittent hypoxia, which is an integral feature of OSAS. The precise role of inflammation in the development of cardiovascular disease in OSAS requires further study, particularly the relationship with oxidative stress, metabolic dysfunction, and obesity.
    • Obstructive sleep apnea in chronic obstructive pulmonary disease patients.

      Lee, Ruth; McNicholas, Walter T; Pulmonary and Sleep Disorders Unit, St. Vincent's University Hospital, Dublin, Ireland. (2011-03)
      Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) represent two of the most prevalent chronic respiratory disorders and cardiovascular diseases are major co-morbidities in both. Co-existence of both disorders (overlap syndrome) occurs in 1% of adults and overlap patients have worse nocturnal hypoxemia and hypercapnia than COPD and OSA patients alone. The present review discusses recent data concerning the pathophysiological and clinical significance of the overlap syndrome.
    • Obstructive sleep apnea in chronic obstructive pulmonary disease patients.

      Lee, Ruth; McNicholas, Walter T; Pulmonary and Sleep Disorders Unit, St. Vincent's University Hospital, Dublin,, Ireland. (2012-02-01)
      PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) represent two of the most prevalent chronic respiratory disorders and cardiovascular diseases are major co-morbidities in both. Co-existence of both disorders (overlap syndrome) occurs in 1% of adults and overlap patients have worse nocturnal hypoxemia and hypercapnia than COPD and OSA patients alone. The present review discusses recent data concerning the pathophysiological and clinical significance of the overlap syndrome. RECENT FINDINGS: The severity of obstructive ventilatory impairment and hyperinflation, especially the inspiratory capacity to total lung capacity (TLC) ratio, correlates with the severity of sleep-related breathing disturbances. Early treatment with continuous positive airway pressure (CPAP) improves survival, reduces hospitalization and pulmonary hypertension, and also reduces hypoxemia. Evidence of systemic inflammation and oxidative stress in COPD and sleep apnea provides insight into potential interactions between both disorders that may predispose to cardiovascular disease. Long-term outcome studies of overlap patients currently underway should provide further evidence of the clinical significance of the overlap syndrome. SUMMARY: Studies of overlap syndrome patients at a clinical, physiological and molecular level should provide insight into disease mechanisms and consequences of COPD and sleep apnea, in addition to identifying potential relationships with cardiovascular disease.
    • Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism.

      Hogan, A M; Kennelly, R; Collins, D; Baird, A W; Winter, D C; Institute for Clinical Outcomes Research and Education, St Vincent's University, Hospital, Dublin, Ireland. (2012-02-01)
      BACKGROUND: Classical effects of oestrogen involve activation of target genes after binding nuclear receptors. Oestrogenic effects too rapid for DNA transcription (non-genomic) are known to occur. The effect of oestrogen on colonic motility is unknown despite the prevalence of gastrointestinal symptoms in pregnant and premenopausal women. METHODS: Histologically normal colon was obtained from proximal resection margins of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended in organ baths under 1 g of tension. After equilibration, they were exposed to 17beta-oestradiol (n = 8) or bovine serum albumin (BSA)-conjugated 17beta-oestradiol (n = 8). Fulvestrant, an oestrogen receptor antagonist, was added to some baths (n = 8). Other strips were exposed to calphostin C or cycloheximide. Carbachol was added in increasing concentrations and contractile activity was recorded isometrically. RESULTS: Oestrogen inhibited colonic contractility (mean difference 19.7 per cent; n = 8, P < 0.001). In keeping with non-genomic, rapid-onset steroid action, the effect was apparent within minutes and reversible. It was observed with both 17beta-oestradiol and BSA-conjugated oestrogen, and was not altered by cycloheximide. Effects were inhibited by fulvestrant, suggesting receptor mediation. CONCLUSION: Oestrogen decreases contractility in human colonic smooth muscle by a non-genomic mechanism involving cell membrane coupling.