Times have changed--Is it time to consider restructuring the CAG?
Explore the source record for details and available documents.
Canada↗
Biomedical subjects
William G Paterson
Publications and source records attributed to William G Paterson.
Functional esophageal disorders.
Functional esophageal disorders represent processes accompanied by typical esophageal symptoms (heartburn, chest pain, dysphagia, globus) that are not explained by structural disorders, histopathology-based motor disturbances, or gastroesophageal reflux disease. Gastroesophageal reflux disease is the preferred diagnosis when reflux esophagitis or excessive esophageal acid exposure is present or when symptoms are closely related to acid reflux events or respond to antireflux therapy. A singular, well-defined pathogenetic mechanism is unavailable for any of these disorders; combinations of sensory and motor abnormalities involving both central and peripheral neural dysfunction have been invoked for some. Treatments remain empirical, although the efficacy of several interventions has been established in the case of functional chest pain. Management approaches that modulate central symptom perception or amplification often are required once local provoking factors (eg, noxious esophageal stimuli) have been eliminated. Future research directions include further determination of fundamental mechanisms responsible for symptoms, development of novel management strategies, and definition of the most cost-effective diagnostic and treatment approaches.
Animals↗
Canadian consensus on medically acceptable wait times for digestive health care.
BACKGROUND: Delays in access to health care in Canada have been reported, but standardized systems to manage and monitor wait lists and wait times, and benchmarks for appropriate wait times, are lacking. The objective of the present consensus was to develop evidence- and expertise-based recommendations for medically appropriate maximal wait times for consultation and procedures by a digestive disease specialist. METHODS: A steering committee drafted statements defining maximal wait times for specialist consultation and procedures based on the most common reasons for referral of adult patients to a digestive disease specialist. Statements were circulated in advance to a multidisciplinary group of 25 participants for comments and voting. At the consensus meeting, relevant data and the results of voting were presented and discussed; these formed the basis of the final wording and voting of statements. RESULTS: Twenty-four statements were produced regarding maximal medically appropriate wait times for specialist consultation and procedures based on presenting signs and symptoms of referred patients. Statements covered the areas of gastrointestinal bleeding; cancer confirmation and screening and surveillance of colon cancer and colonic polyps; liver, biliary and pancreatic disorders; dysphagia and dyspepsia; abdominal pain and bowel dysfunction; and suspected inflammatory bowel disease. Maximal wait times could be stratified into four possible acuity categories of 24 h, two weeks, two months and six months. FUTURE DIRECTIONS: Comparison of these benchmarks with actual wait times will identify limitations in access to digestive heath care in Canada. These recommendations should be considered targets for future health care improvements and are not clinical practice guidelines.
Canada↗
Excitatory purinergic neurotransmission in smooth muscle of guinea-pig [corrected] taenia caeci.
Non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmission has been an area of intense interest in gut motor physiology, whereas excitatory NANC neurotransmission has received less attention. In order to further explore excitatory NANC neurotransmission, we performed conventional intracellular recordings from guinea-pig taenia caeci smooth muscle. Tissue was perfused with oxygenated Krebs solution at 35 degrees C and nerve responses evoked by either oral or aboral nerve stimulation (NS) (4 square wave pulses, 0.3 ms duration, 20 Hz). Electrical activity was characterized by slow waves upon which one to three action potentials were superimposed. Oral NS evoked an inhibitory junction potential (IJP) at either the valley or peak of the slow wave. Application of nifedipine (1 microM) abolished slow waves and action potentials, but membrane potential flunctuations (1-3 mV) and IJPs remained unaffected. Concomitant application of apamin (300 nM), a small-conductance Ca(2+)-activated K(+) channel blocker, converted the IJP to an EJP that was followed by slow IJP. Further administration of N(G)-nitro-l-arginine methyl ester (l-NAME, 200 microM), a nitric oxide synthase inhibitor, abolished the slow IJP without affecting the EJP, implying that the slow IJP is due to nitrergic innervation. The EJP was abolished by tetrodotoxin (1 microM), but was not significantly affected by atropine (3 microM) and guanethidine (3 microM) or hexamethonium (500 microM). Substance P (SP, 1 microM) desensitization caused slight attenuation of the EJP, but the EJP was abolished by desensitization with alpha,beta-methylene ATP (50 microM), a P2 purinoceptor agonist that is more potent than ATP at the P2X receptor subtype, suramin (100 microM), a non-selective P2 purinoceptor antagonist, and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 100 microM) , a selective P2X purinoceptor antagonist. In contrast, the EJP was unaffected by MRS-2179 (2 microM), a selective P2Y(1) receptor antagonist. Aboral NS evoked an apamin- and l-NAME-sensitive IJP, but virtually no NANC EJP. These data suggest the presence of polarized excitatory purinergic neurotransmission in guinea-pig taenia caeci, which appears to be mediated by P2X purinoceptors, most likely the P2X(1) subtype.
Action Potentials↗
Morphology and glycoconjugate content of opossum esophageal epithelium and glands: regional heterogeneity and effects of acid-induced mucosal injury and recovery.
This study examined the regional heterogeneity and site-specific changes in histology and glycoconjugate content following the induction of esophagitis and after recovery in an established animal model. Esophageal samples were excised from five sites in anesthetized opossums 24 hr after 3 consecutive days of 45-min perfusion with saline or 100 mM HCl or 1 week after acid in recovery animals. Controls exhibited significant regional differences in epithelial thickness, gland volume, glycoconjugate composition, and mast cell numbers. Acid perfusion induced erosive esophagitis and significant epithelial denudation throughout the distal 7 cm, combined with significant site-specific increases in gland lumen volume, decreases in mast cell numbers, and changes in glycoconjugate content. No differences from controls were noted in recovery animals, except for a significant increase in epithelial thickness and change in glycoconjugate content in the distal 2 cm. The results of this study highlight the impact of acid exposure on these structural defenses, but further investigation is required to explore the importance of these acid-induced changes in the pathogenesis of reflux esophagitis.
Animals↗
Canadian Consensus Conference on the management of gastroesophageal reflux disease in adults - update 2004.
BACKGROUND: Gastroesophageal reflux disease (GERD) is the most prevalent acid-related disorder in Canada and is associated with significant impairment of health-related quality of life. Since the last Canadian Consensus Conference in 1996, GERD management has evolved substantially. OBJECTIVE: To develop up-to-date evidence-based recommendations relevant to the needs of Canadian health care providers for the management of the esophageal manifestations of GERD. CONSENSUS PROCESS: A multidisciplinary group of 23 voting participants developed recommendation statements using a Delphi approach; after presentation of relevant data at the meeting, the quality of the evidence, strength of recommendation and level of consensus were graded by participants according to accepted principles. OUTCOMES: GERD applies to individuals who reflux gastric contents into the esophagus causing symptoms sufficient to reduce quality of life, injury or both; endoscopy-negative reflux disease applies to individuals who have GERD and a normal endoscopy. Uninvestigated heartburn-dominant dyspepsia - characterised by heartburn or acid regurgitation - includes erosive esophagitis or endoscopy-negative reflux disease, and may be treated empirically as GERD without further investigation provided there are no alarm features. Lifestyle modifications are ineffective for frequent or severe GERD symptoms; over-the-counter antacids or histamine H2-receptor antagonists are effective for some patients with mild or infrequent GERD symptoms. Proton pump inhibitors are more effective for healing and symptom relief than histamine H2-receptor antagonists; their efficacy is proportional to their ability to reduce intragastric acidity. Response to initial therapy - a once-daily proton pump inhibitor unless symptoms are mild and infrequent (fewer than three times per week) - should be assessed at four to eight weeks. Maintenance medical therapy should be at the lowest dose and frequency necessary to maintain symptom relief; antireflux surgery is an alternative for a small proportion of selected patients. Routine testing for Helicobacter pylori infection is unnecessary before starting GERD therapy. GERD is associated with Barrett's epithelium and esophageal adenocarcinoma but the risk of malignancy is very low. Endoscopic screening for Barrett's epithelium may be considered in adults with GERD symptoms for more than 10 years; Barrett's epithelium and low-grade dysplasia generally warrant surveillance; endoscopic or surgical management should be considered for confirmed high-grade dysplasia or malignancy. CONCLUSION: Prospective studies are needed to investigate clinically relevant risk factors for the development of GERD and its complications; GERD progression, on and off therapy; optimal management strategies for typical GERD symptoms in primary care patients; and optimal management strategies for atypical GERD symptoms, Barrett's epithelium and esophageal adenocarcinoma.
Adult↗
GI stromal tumor unmasked by argon plasma coagulation of vascular ectasia.
Explore the source record for details and available documents.
Adult↗
Role of sarcoplasmic reticulum in control of membrane potential and nitrergic response in opossum lower esophageal sphincter.
1. We previously demonstrated that a balance of Ca2+-activated Cl- current (ICl(Ca)) and K+ current activity sets the resting membrane potential of opossum lower esophageal sphincter (LES) circular smooth muscle at approximately -41 mV, which leads to continuous spike-like action potentials and the generation of basal tone. Ionic mechanisms underlying this basal ICl(Ca) activity and its nitrergic regulation remain unclear. Recent studies suggest that spontaneous Ca2+ release from sarcoplasmic reticulum (SR) and myosin light chain kinase (MLCK) play important roles. The current study investigated this possibility. Conventional intracellular recordings were performed on circular smooth muscle of opossum LES. Nerve responses were evoked by electrical square wave pulses of 0.5 ms duration at 20 Hz. 2. In the presence of nifedipine (1 microm), substance P (1 microm), atropine (3 microm) and guanethidine (3 microm), intracellular recordings demonstrated a resting membrane potential (MP) of -38.1+/-0.7 mV (n=25) with spontaneous membrane potential fluctuations (MPfs) of 1-3 mV. Four pulses of nerve stimulation induced slow inhibitory junction potentials (sIJPs) with an amplitude of 6.1+/-0.3 mV and a half-amplitude duration of 1926+/-147 ms (n=25). 3. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a specific guanylyl cyclase inhibitor, abolished sIJPs, but had no effects on MPfs. Caffeine, a ryanodine receptor agonist, hyperpolarized MP and abolished sIJPs and MPfs. Ryanodine (20 microm) inhibited the sIJP and induced biphasic effects on MP, an initial small hyperpolarization followed by a large depolarization. sIJPs and MPfs were also inhibited by cyclopiazonic acid, an SR Ca2+ ATPase inhibitor. Specific ICl(Ca) and MLCK inhibitors hyperpolarized the MP and inhibited MPfs and sIJPs. 4. These data suggest that (1). spontaneous release of Ca2+ from the SR activates ICl(Ca), which in turn contributes to resting membrane potential; (2). MLCK is involved in activation of ICl(Ca); (3). inhibition of ICl(Ca) is likely to underlie sIJPs induced by nitrergic innervation.
Animals↗
Fluid restriction for postoperative patients?
Explore the source record for details and available documents.
Colonic Diseases↗
Analysis of mucosal stress response in acid-induced esophagitis in opossum.
This study is the first to examine site-specific changes in mucosal antioxidants and expression and localization of heat shock proteins (HSPs) following the induction of subacute esophagitis and after recovery using an established animal model. Distal, middle, and proximal samples were excised from anesthetized opossums 24 hr after three consecutive days of 45-min perfusion with saline or 100 mmol/liter HCI, or seven days after acid in recovery animals. Compared to controls, acid-induced erosive esophagitis significantly increased glutathione peroxidase and HSP90 at all sites and HSP60 proximally. Reduced glutathione was significantly decreased distally, as was HSP72 at distal and middle sites. No changes in superoxide dismutase or catalase occurred. After recovery, superoxide dismutase, catalase, and HSP expression were not different from controls. Glutathione peroxidase and glutathione were significantly decreased distally. Similar differential stress responses may occur in patients with chronic gastroesophageal reflux and could be important in the pathogenesis of reflux esophagitis.
Acids↗
Gastrointestinal promotility drugs in the critical care setting: a systematic review of the evidence.
CONTEXT: Gastrointestinal promotility agents may improve tolerance to enteral nutrition, reduce gastroesophageal reflux and pulmonary aspiration, and therefore have the potential to improve outcomes of critically ill patients. OBJECTIVE: To systematically review and critically appraise studies of promotility agents in the critical care setting. DATA SOURCES: Computerized bibliographic search of published research (1980-2001), citation review of relevant articles, and contact with primary investigators. STUDY SELECTION: Randomized trials of critically ill adult patients that evaluated the effect of promotility agents on measures of gastrointestinal motility were included. DATA EXTRACTION: Relevant methods and outcome data were abstracted in duplicate by independent investigators. DATA SYNTHESIS: We reviewed 60 citations; 18 articles met the inclusion criteria (six studies of feeding tube placement, 11 studies evaluating gastrointestinal function, and one study of clinical outcomes). The heterogeneity of study methods and outcomes measured precluded a quantitative synthesis of the data. Although there are conflicting studies, the larger and more methodologically robust studies suggest that metoclopramide has no effect on feeding tube placement. Erythromycin has been shown to increase success rates with small-bowel tube placement in two studies. Eight of ten studies evaluating the effect of cisapride, metoclopramide, or erythromycin on measures of gastrointestinal transit demonstrated positive effects; the two studies that did not were relatively small (n = 27 and 10) and likely had inadequate power to detect a difference in treatment effect. No study demonstrated a positive effect on clinical outcomes. CONCLUSIONS: As a class of drugs, promotility agents appear to have a beneficial effect on gastrointestinal motility in critically ill patients. A one-time dose of erythromycin may facilitate small-bowel feeding tube insertion. Administration of metoclopramide appears to increase physiologic indexes of gastrointestinal transit and feeding tolerance. Concerns about safety and lack of effect on clinically important outcomes preclude strong treatment recommendations.
Critical Care↗
The IBS-36: a new quality of life measure for irritable bowel syndrome.
OBJECTIVE: We aimed to develop and validate a quality of life instrument for patients with irritable bowel syndrome (IBS). METHODS: Using focus groups, existing questionnaires, and literature reviews, five IBS patients and nine gastroenterologists compiled and pilot tested for content validity a 70-item questionnaire. The questionnaire was then administered to 107 IBS patients, and using these data, the 70-item questionnaire was reduced to 36 questions through statistical and consensus methodology. The IBS-36 questionnaire was tested for construct validity, reliability, reproducibility, and responsiveness using a gold standard of structured interviews by three gastroenterologists, the Medical Outcomes Study Short Form Quality of Life Questionnaire, and the Coping Resource Inventory. RESULTS: The IBS-36 consists of 36 questions scored on a 7-point Likert scale. It has a very high internal consistency (Cronbach's alpha = 0.95) and a high test-retest reliability (Spearman's r = 0.92) and correlates as hypothesized with the Medical Outcomes Study Short Form Quality of Life Questionnaire (p < 0.001), McGill pain scores (p < 0.001), and IBS patient-reported sleep, symptom, and pain scores (ps = 0.030, <0.001, and <0.001, respectively). CONCLUSIONS: The IBS-36 addresses all areas of quality of life affected by IBS and is easy to administer and score. The IBS-36 is a well-validated, condition-specific quality of life measure for IBS patients that is sensitive to clinical intervention and highly correlated with established quality of life measures and patient-reported symptom scores.
Adolescent↗
Role of Ca2+-activated Cl- channels and MLCK in slow IJP in opossum esophageal smooth muscle.
The possible contribution of Ca2+-activated Cl- channel [I(Cl(Ca))] and myosin light-chain kinase (MLCK) to nonadrenergic, noncholinergic slow inhibitory junction potentials (sIJP) was studied using conventional intracellular microelectrode recordings in circular smooth muscle of opossum esophageal body and guinea pig ileum perfused with Krebs solution containing atropine (3 microM), guanethidine (3 microM), and substance P (1 microM). In opossum esophageal circular smooth muscle, resting membrane potential (MP) was -51.9 +/- 0.7 mV (n = 89) with MP fluctuations of 1-3 mV. A single square-wave nerve stimulation of 0.5 ms duration and 80 V induced a sIJP with amplitude of 6.3 +/- 0.2 mV, half-amplitude duration of 635 +/- 19 ms, and rebound depolarization amplitude of 2.4 +/- 0.1 mV (n = 89). 9-Anthroic acid (A-9-C), niflumic acid (NFA), wortmannin, and 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9) abolished MP fluctuations, sIJP, and rebound depolarization in a concentration-dependent manner. A-9-C and NFA but not wortmannin and ML-9 hyperpolarized MP. In guinea pig ileal circular smooth muscle, nerve stimulation elicited an IJP composed of both fast (fIJP) and slow (sIJP) components, followed by rebound depolarization. NFA (200 microM) abolished sIJP and rebound depolarization but left the fIJP intact. These data suggest that in the tissues studied, activation of I(Cl(Ca)), which requires MLCK, contributes to resting MP, and that closing of I(Cl(Ca)) is responsible for sIJP.
Androstadienes↗
The lower esophageal sphincter.
Explore the source record for details and available documents.
Esophageal Diseases↗