• Aging and intestinal motility: a review of factors that affect intestinal motility in the aged.

      O'Mahony, Denis; O'Leary, Paula; Quigley, Eamonn M M; Department of Medicine, Clinical Sciences Building, Cork University Hospital,, Cork, Ireland. (2012-02-03)
      Normal aging is associated with significant changes in the function of most organs and tissues. In this regard, the gastrointestinal tract is no exception. The purpose of this review is to detail the important age-related changes in motor function of the various parts of the gastrointestinal tract and to highlight some of the important motility changes that may occur, either in relation to common age-related disorders, or as a result of certain drugs commonly prescribed in the aged. A major confounding factor in the interpretation of motor phenomena throughout the gastrointestinal tract in this age group is the frequent coexistence of neurological, endocrinological and other disease states, which may be independently associated with dysmotility. Overall, current data are insufficient to implicate normal aging as a cause of dysmotility in the elderly. Normal aging is associated with various changes in gastrointestinal motility, but the clinical significance of such changes remains unclear. More important is the impact of various age-related diseases on gastrointestinal motility in the elderly: for example, long-standing diabetes mellitus may reduce gastric emptying in up to 50% of patients; depression significantly prolongs whole-gut transit time; hypothyroidism may prolong oro-caecal transit time; and chronic renal failure is associated with impaired gastric emptying. In addition, various, frequently used drugs in the elderly cause disordered gastrointestinal motility. These drugs include anticholinergics, especially antidepressants with an anticholinergic effect, opioid analgesics and calcium antagonists.
    • Autoimmune hepatitis in association with lymphocytic colitis.

      Cronin, Edmond M; Sibartie, Vikrant; Crosbie, Orla M; Quigley, Eamonn M M; Department of Gastroenterology, Cork University Hospital, Wilton, Cork, Ireland. , ecronin10@hotmail.com (2012-02-03)
      Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.
    • 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.
    • 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.
    • CT-based estimation of intracavitary gas volumes using threshold-based segmentation: in vitro study to determine the optimal threshold range.

      McWilliams, Sebastian Robert; O'Connor, Owen J; McGarrigle, Anne Marie; O'Neill, Siobhan B; Quigley, Eamonn M M; Shanahan, Fergus; Maher, Michael M; Department of Radiology, University College Cork, Cork University Hospital, Wilton, Cork, Ireland. sebastian.mcwilliams@gmail.com (2012-06)
      This study investigated the optimal Hounsfield unit (HU) threshold range when using threshold-based segmentation to estimate volumes of contained gas (i.e. intestinal gas) on CT.
    • Differential expression of toll-like receptors in patients with irritable bowel syndrome.

      Brint, Elizabeth K; MacSharry, John; Fanning, Aine; Shanahan, Fergus; Quigley, Eamonn M M; Department of Pathology, University College Cork, National University of Ireland, and Alimentary Pharmabiotic Centre, Cork University Hospital, Cork, Ireland. e.brint@ucc.ie (2011-02)
      The pathogenesis of irritable bowel syndrome (IBS) is poorly understood. One contributory factor may be low-grade mucosal inflammation, perhaps initiated by the microbiota. Toll-like receptors (TLRs) are a family of pathogen-recognition receptors of the innate immune system. The aim of this study was to evaluate the potential involvement of TLRs in IBS to further understand the involvement of the innate immune system in this complex disorder.
    • Disturbances of motility and visceral hypersensitivity in irritable bowel syndrome: biological markers or epiphenomenon.

      Quigley, Eamonn M M; Department of Medicine, Alimentary Pharmabiotic Centre, Cork University Hospital,, Clinical Sciences Building, Cork, Ireland. e.quigley@ucc.ie (2012-02-03)
      Motility and visceral hypersentitivity are regarded as the primary mechanisms of symptom development in irritable bowel syndrome(IBS). While a variety of motor abnormalities have been described throughout the gastrointestinal tract in IBS, their specificity and relationship to symptoms remain unclear. Visceral hypersensitivity is ubiquitous in functional gastrointestinal disease and is especially common in IBS. Again, however, its specificity for IBS has been questioned. Many factors, including stress and psychopathology,complicate the interpretation of these phenomena and new re-search suggests that mucosal inflammation and luminal factors may be more fundamental to the etiology of this common disorder.
    • Factors that influence therapeutic outcomes in symptomatic gastroesophageal reflux disease.

      Quigley, Eamonn M M; Department of Medicine, Clinical Sciences Building, Cork University Hospital,, National University of Ireland, Wilton Road, Cork, Ireland. (2012-02-03)
      The term "symptomatic gastroesophageal reflux disease" (GERD) refers to those patients who present with the typical GERD symptoms of heartburn and regurgitation, yet do not have endoscopic evidence of esophagitis. The primary goals of managing symptomatic GERD are to control symptoms and improve quality of life. A clinical assessment of the GERD patient can identify important clinical features, such as atypical and extraesophageal symptoms for which acid-suppressive agents tend to be less effective. Performing an endoscopy can further identify the patient as having nonerosive reflux disease, erosive esophagitis, or Barrett's esophagus-diagnoses which can help determine treatment but may not prove predictive of therapeutic response. Determining acid exposure through pH testing can predict therapeutic response, with those revealing an abnormal acid exposure time being more responsive to acid-suppressive therapy. However, the performance of an endoscopy and pH testing on each patient is clearly not practical. Whereas the natural history of symptomatic GERD is still largely undefined, acid-suppressive therapy appears to be the best approach available for both the short-term and long-term management of this disease.
    • Functional dyspepsia (FD) and non-erosive reflux disease (NERD): overlapping or discrete entities?

      Quigley, Eamonn M M; Department of Medicine, Cork University Hospital, Clinical Sciences Building,, Cork, Ireland. e.quigley@ucc.ie (2012-02-03)
      As the incidence of both gastric cancer and peptic ulcer disease have declined, that of gastro-oesophageal reflux disease (GORD) and non-ulcer, or functional dyspepsia (FD) have reached virtually epidemic proportions. As we come to appreciate the expression of these disorders in the community, the real spectrum of each disease has become evident. FD and non-erosive reflux disease (NERD), the most prevalent manifestation of GORD, frequently overlap. Where then does GORD end and FD begin? Is it realistic, or even clinically relevant, to attempt a clear separation between these entities? These are more than issues of mere semantics; therapeutic options may be dictated by the classification of the patient as one or the other. Recent work indicates clearly that NERD is a heterogeneous disorder incorporating some patients who may well harbour subtle manifestations of oesophagitis and others who have entirely normal 24-hour pH studies. These differences may be crucial to the concept of NERD/FD overlap. While evidence in support of this concept is far from complete, it would appear that this overlap is most relevant to those NERD patients who do not exhibit abnormal esophageal acid exposure. These patients truly belong in the spectrum of functional gastrointestinal disorders rather than in GORD; attempts to shoe-horn these individuals into the spectrum of GORD will result in therapeutic disappointment and surgical disaster.
    • Functional dyspepsia: the role of visceral hypersensitivity in its pathogenesis.

      Keohane, John; Quigley, Eamonn M M; Department of Medicine, Alimentary Pharmabiotic Centre, Clinical Sciences, Building, Cork University Hospital, Cork, Ireland. (2012-02-03)
      Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.
    • A global perspective on irritable bowel syndrome: a consensus statement of the World Gastroenterology Organisation Summit Task Force on irritable bowel syndrome.

      Quigley, Eamonn M M; Abdel-Hamid, Hussein; Barbara, Giovanni; Bhatia, Shobna J; Boeckxstaens, Guy; De Giorgio, Roberto; Delvaux, Michel; Drossman, Douglas A; Foxx-Orenstein, Amy E; Guarner, Francisco; et al. (2012-08-15)
      Irritable bowel syndrome (IBS) is common in western Europe and North America, and many aspects of its epidemiology, risk factors, and natural history have been described in these regions. Recent data suggest, however, that IBS is also common in the rest of the world and there has been some evidence to suggest some differences in demographics and presenting features between IBS in the west and as it is experienced elsewhere. The World Gastroenterology Organization, therefore, established a Task Force comprising experts on the topic from all parts of the world to examine IBS from a global perspective. IBS does, indeed, seem to be common worldwide though with some significant variations in prevalence rates between regions and countries and there may well be some potentially interesting variations in presenting symptoms and sex distribution. The global map of IBS is far from complete; community-based prevalence data is not available from many areas. Furthermore, while some general trends are evident in terms of IBS impact and demographics, international comparisons are hampered by differences in diagnostic criteria, study location and methodology; several important unanswered questions have been identified that should form the basis for future collaborative research and have the potential to shed light on this challenging disorder.
    • Irritable bowel syndrome: role of food in pathogenesis and management.

      Morcos, Ashraf; Dinan, Ted; Quigley, Eamonn M M; Department of Gastroenterology and Internal Medicine, Midwestern Regional Hospital, Limerick, Ireland. (2009-11)
      Patients with the irritable bowel syndrome (IBS) commonly report the precipitation of symptoms on food ingestion. Though the role of dietary constituents in IBS has not been extensively studied, food could contribute to symptom onset or even the causation of IBS through a number of mechanisms. First, the physiological response of the intestine to food ingestion could precipitate symptoms in predisposed individuals; second, there is some evidence that allergy or intolerance to a particular food can produce IBS-like symptoms, third, certain foods may alter the composition of the luminal milieu, either directly or indirectly through effects on bacterial metabolism, and thus induce symptoms and, finally, IBS may develop following exposure to food-borne pathogens. Anticipatory, psychological factors generated by previous negative experiences with food ingestion or other factors may also contribute though their contribution has been scarcely quantified. Not surprisingly, there is considerable interest in the potential roles of diet and food supplements in the therapy of IBS; for the most part, the evidence base for such recommendations remains slim though certain probiotics show considerable promise.
    • Management of chronic constipation in the elderly.

      Gallagher, Paul F; O'Mahony, Denis; Quigley, Eamonn M M; Department of Geriatric Medicine, Cork University Hospital, Alimentary, Pharmabiotic Centre, University College Cork, Cork, Ireland. (2012-02-03)
      Constipation is a significant healthcare problem in the elderly. However, while undoubtedly common in the elderly, data on the prevalence of constipation in general and of its subtypes vary considerably, depending on the nature of the study population and their location. Furthermore, the complexity of the pathophysiology of constipation in this age group is little appreciated. Assumptions regarding 'age-related changes in colorectal physiology' are, for the most part, not supported by scientific evidence and may serve to distract the clinician from uncovering the contributions of co-morbid diseases and the impact of iatrogenic factors. The evidence base from which one can develop recommendations on the management of constipation in the elderly is, for the most part, slim. This becomes most starkly apparent when one attempts to critically assess specific approaches to management. There is insufficient evidence to support the use of many commonly used laxatives both in the general population and in the elderly. Lifestyle interventions have value for some patients but data are lacking on the benefits of these interventions for patients with chronic constipation. Data in the elderly do not exist for most new pharmacological approaches to constipation. Pending the availability of good data, management of constipation in the elderly should be tailored to each individual's needs and expectations, regardless of age or place of residence. In certain situations, constipation may be complicated by the development of impaction; preventive strategies are important in this context. We urge enrolment of many more elderly individuals with chronic constipation in clinical trials designed to address their particular needs.
    • A molecular analysis of fecal and mucosal bacterial communities in irritable bowel syndrome.

      Codling, Caroline; O'Mahony, Liam; Shanahan, Fergus; Quigley, Eamonn M M; Marchesi, Julian R; Department of Medicine, Alimentary Pharmabiotic Centre, Cork University Hospital, Cork, Ireland. (2010-02)
      The objectives of this study were, firstly, to determine the diversity of the host's gut microbiota in irritable bowel syndrome (IBS) using a culture-independent method (DGGE of the 16S rRNA gene) and, secondly, to examine mucosal biopsies of IBS patients and compare them to their own fecal microbiota.
    • Prebiotics and probiotics: their role in the management of gastrointestinal disorders in adults.

      Quigley, Eamonn M M; Alimentary Pharmabiotic Centre, Department of Medicine,Cork University Hospital, Cork, Ireland. e.quigley@ucc.ie (2012-04)
      For decades, if not centuries, a variety of products with what would now be regarded as prebiotic and probiotic properties have been consumed by the general public and advocated for their benefits on health and, in particular, gastrointestinal well-being. More recently, medical science has taken a great interest in the population of micro-organisms, the gut microbiota that normally populates the human gut, and the range of important functions carried out by the microbiota in health is being progressively defined. As a corollary, the list of disorders and diseases that may result from disruption of the normal microbiota and/or its interaction with the host continues to grow. A scientific basis for the use of probiotics and prebiotics is, therefore, beginning to emerge. Unfortunately, although progress has been made, the clinical evidence to support the use of these preparations lags behind. Nevertheless, a number of human disease states may benefit from the use of probiotics, most notably, diarrheal illnesses, some inflammatory bowel diseases, certain infectious disorders, and irritable bowel syndrome. Prebiotics promote the growth of "good" bacteria, and although a variety of health benefits have been attributed to their use, prebiotics have been subjected to few large-scale clinical trials.
    • Prebiotics for irritable bowel syndrome.

      Quigley, Eamonn M M; Alimentary Pharmabiotic Centre, University College Cork, and Department of Medicine, Clinical Sciences Building, Cork University Hospital, Cork, Ireland. e.quigley@ucc.ie (2009-10)
    • Safety and tolerability of tegaserod in patients with chronic constipation: pooled data from two phase III studies.

      Quigley, Eamonn M M; Wald, Arnold; Fidelholtz, James; Boivin, Michel; Pecher, Eckhard; Earnest, David; Alimentary Pharmabiotic Centre, Department of Medicine, Cork University Hospital,, Wilton, Cork, Ireland. e.quigley@ucc.ie (2012-02-03)
      BACKGROUND & AIMS: Studies show that tegaserod effectively relieves the symptoms of chronic constipation/idiopathic constipation (CC). This pooled analysis assessed the safety and tolerability of tegaserod in a large dataset of CC patients. METHODS: Adverse event (AE) data were pooled from 2 double-blind, placebo-controlled phase III trials of 12 weeks' duration. Post hoc analysis was conducted for the most frequent AEs (incidence, >or=3%). RESULTS: Eight hundred eighty-one, 861, and 861 patients received tegaserod 6 mg twice a day, 2 mg twice a day, or placebo, respectively. Most AEs were mild/moderately severe. AE incidence was similar for the tegaserod 6 mg and 2 mg twice a day (57.1% and 56.3%, respectively) and placebo groups (59.6%) and most frequent in the gastrointestinal system (tegaserod 6 mg twice a day, 25.8%; 2 mg twice a day, 22.5%; placebo, 24.6%). Headache, the most common AE, was slightly more frequent in the placebo group (tegaserod 6 mg twice a day, 11.0%; 2 mg twice a day, 10.1%; placebo, 13.2%). Diarrhea (generally transient and resolved with continued treatment) was the only AE with a statistically significant difference between groups (tegaserod 6 mg twice a day 6.6% vs placebo 3.0%, P=.0005). Serious AE incidence (1.4% overall) was comparable across treatment groups, although abdominal surgery was less common in the combined tegaserod (0.5%) than the placebo group (1.0%). Discontinuation as a result of AEs was slightly higher in tegaserod 6 mg twice a day patients (5.7%; 2 mg twice a day, 3.3%; placebo, 3.7%), mainly because of diarrhea. Laboratory and electrocardiogram parameters were comparable across groups. CONCLUSIONS: Tegaserod is well tolerated by patients with CC during 12 weeks of treatment.
    • Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8.

      Shanab, Ahmed Abu; Scully, Paul; Crosbie, Orla; Buckley, Martin; O'Mahony, Liam; Shanahan, Fergus; Gazareen, Sanaa; Murphy, Eileen; Quigley, Eamonn M M; Alimentary Pharmabiotic Centre, Department of Medicine, University College Cork, National University of Ireland, Cork, Ireland. (Springer, 2011-05)
      Experimental and clinical studies suggest an association between small intestinal bacterial overgrowth (SIBO) and nonalcoholic steatohepatitis (NASH). Liver injury and fibrosis could be related to exposure to bacterial products of intestinal origin and, most notably, endotoxin, including lipopolysaccharide (LPS).
    • Therapies aimed at the gut microbiota and inflammation: antibiotics, prebiotics, probiotics, synbiotics, anti-inflammatory therapies.

      Quigley, Eamonn M M; Department of Medicine, Alimentary Pharmabiotic Centre, Cork University Hospital, University College Cork, Clinical Sciences Building, Cork, Ireland. e.quigley@ucc.ie (2011-03)
      Several recent observations have raised the possibility that disturbances in the gut microbiota and/or a low-grade inflammatory state may contribute to symptomatology and the etiology of irritable bowel syndrome (IBS). Consequent on these hypotheses, several therapeutic categories have found their way into the armamentarium of those who care for IBS sufferers. These agents include probiotics, prebiotics, antibiotics, and anti-inflammatory agents.