[Show abstract][Hide abstract] ABSTRACT: Bitter taste receptors (TAS2Rs) are present in extra-oral tissues, including gut endocrine cells. This study explored the presence and mechanism of action of TAS2R agonists on gut smooth muscle in vitro and investigated functional effects of intra-gastric administration of TAS2R agonists on gastric motility and satiation. TAS2Rs and taste signalling elements were expressed in smooth muscle tissue along the mouse gut and in human gastric smooth muscle cells (hGSMC). Bitter tastants induced concentration and region-dependent contractility changes in mouse intestinal muscle strips. Contractions induced by denatonium benzoate (DB) in gastric fundus were mediated via increases in intracellular Ca2+ release and extracellular Ca2+-influx, partially masked by a hyperpolarizing K+-efflux. Intra-gastric administration of DB in mice induced a TAS2R-dependent delay in gastric emptying. In hGSMC, bitter compounds evoked Ca2+-rises and increased ERK-phosphorylation. Healthy volunteers showed an impaired fundic relaxation in response to nutrient infusion and a decreased nutrient volume tolerance and increased satiation during an oral nutrient challenge test after intra-gastric DB administration. These findings suggest a potential role for intestinal TAS2Rs as therapeutic targets to alter gastrointestinal motility and hence to interfere with hunger signalling.
[Show abstract][Hide abstract] ABSTRACT: The efficacy of gastric neurostimulation therapy for diabetic gastroparesis (GP) in a 'real-life' Canadian setting has not been assessed.
To assess changes in health-related quality of life (QoL), weekly vomiting frequency (WVF), total symptom score (TSS) and health care utilization 12 months before and after gastric neurostimulator implantation in a diabetic GP cohort.
Medication-refractory diabetic GP patients (n=7, four female, mean age 42 years) were prospectively recruited from 2008 to 2012. QoL scores were self-administered and obtained at baseline, 24 and 48 weeks postimplantion. WVF and TSS were assessed similarly. Health care usage, measured as hospitalization frequency and medication cost, was obtained six and 12 months before and after implant. Changes from baseline to six and 12 months for all outcomes were compared.
The mean (± SD) QoL according to EuroQol was significantly better at 24 weeks after the baseline measurement (baseline 29±5, 24 weeks 52±7; P=0.03). The mean improvement in TSS was significantly better at one year postintervention (baseline score 35±5 versus 12 months 27±3; P=0.03). Changes in Short-Form 36 Health Survey and WVF were not significant. Days of GP-related hospitalization were highly variable but decreased from a median of 71 days (range 0 to 227 days) to 29 days (range two to 334 days) one year before and after surgery, respectively (P=0.735). Outpatient medication costs did not decrease to a significant extent.
Gastric neurostimulation for diabetic GP appeared to show some beneficial palliative effects overall in the present small open-label series, but the effect is highly variable among patients, and placebo effect cannot be ruled out.
[Show abstract][Hide abstract] ABSTRACT: Transcutaneous intraluminal impedance measurement (TIIM) is a new method to cutaneously measure gastric contractions by assessing the attenuation dynamics of a small oscillating voltage emitted by a battery-powered ingestible capsule retained in the stomach. In the present study, we investigated whether TIIM can reliably assess gastric motility in acute canine models. Methods. Eight mongrel dogs were randomly divided into 2 groups: half received an active TIIM pill and half received an identically sized sham capsule. After 24-hour fasting and transoral administration of the pill (active or sham), two force transducers (FT) were sutured onto the antral serosa at laparotomy. After closure, three standard cutaneous electrodes were placed on the abdomen, registering the transluminally emitted voltage. Thirty-minute baseline recordings were followed by pharmacological induction of gastric contractions using neostigmine IV and another 30-minute recording. Normalized one-minute baseline and post-neostigmine gastric motility indices (GMIs) were calculated and Pearson correlation coefficients (PCCs) between cutaneous and FT GMIs were obtained. Statistically significant GMI PCCs were seen in both baseline and post-neostigmine states. There were no significant GMI PCCs in the sham capsule test. Further chronic animal studies of this novel long-term gastric motility measurement technique are needed before testing it on humans.
Gastroenterology Research and Practice 11/2014; 2014:1-9. DOI:10.1155/2014/691532 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cyclic vomiting syndrome (CVS) is a chronic disorder characterized by episodic nausea and vomiting. A large proportion of patients use marijuana to control their symptoms. Several case reports implicate marijuana as a cause of intractable vomiting with compulsive hot water bathing considered pathognomonic of "cannabinoid hyperemesis." We sought to examine the relationship between marijuana use and CVS. Patients >18 years of age diagnosed by a health care provider were invited to participate in an anonymous internet-based survey. A total of 514 patients participated and 437 completed questions about marijuana use. Mean age was 34 ± 12 years with patients being predominantly female (63 %), Caucasian (92 %) and from the USA (82 %). Nineteen percent never used marijuana and 81 % did. Fifty-four percent used marijuana for health issues and 43 % for recreational purposes. Users stated that it improved nausea, appetite, general well-being, stress levels and vomiting. Users were more likely to be male and have an associated anxiety disorder. Sixty-seven percent of patients reported taking hot showers/baths for symptom relief, and this was associated with marijuana use. (OR 2.54, CI 1.50-4.31, P = 0.0006). Eighty-one percent of patients with CVS who completed an internet survey reported frequent use of marijuana. With marijuana use, patients noted the greatest improvement with stress levels, appetite and nausea. Marijuana users were more likely to be male and have associated anxiety. Hot showers were not pathognomonic of marijuana use though they were more likely to be associated with its use.
Experimental Brain Research 05/2014; 232(8). DOI:10.1007/s00221-014-3967-0 · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gastroesophageal reflux (GER) is a common gastrointestinal process that can generate symptoms of heartburn and chest pain. Proton pump inhibitors (PPIs) are the gold standard for the treatment of GER; however, a substantial group of GER patients fail to respond to PPIs. In the past, it was believed that acid reflux into the esophagus causes all, or at least the majority, of symptoms attributed to GER, with both erosive esophagitis and nonerosive outcomes. However, with modern testing techniques it has been shown that, in addition to acid reflux, the reflux of nonacid gastric and duodenal contents into the esophagus may also induce GER symptoms. It remains unknown how weakly acidic or alkaline refluxate with a pH similar to a normal diet induces GER symptoms. Esophageal hypersensitivity or functional dyspepsia with superimposed heartburn may be other mechanisms of symptom generation, often completely unrelated to GER. Detailed studies investigating the pathophysiology of esophageal hypersensitivity are not conclusive, and definitions of the various disease states may overlap and are often confusing. The authors aim to clarify the pathophysiology, definition, diagnostic techniques and medical treatment of patients with heartburn symptoms who fail PPI therapy.
[Show abstract][Hide abstract] ABSTRACT: Cannabis has been used to treat various afflictions throughout the centuries, including nausea, vomiting, and pain. It has also been used recreationally for its psychotropic properties, which can include a pleasurable ‘high’ feeling and a decrease in anxiety and tension; however, other may experience dysphoria. Changes in cognition and psychomotor performance are also well-known with cannabis use. In recent years, our understanding of the endocannabinoid system (ECS) has progressed dramatically; the objective of identifying agents which may allow modulation of the ECS without significant psychotropic side effects may be possible. Inhibition of fatty acid amide hydrolase (FAAH), an important enzyme for the degradation of anandamide and other endogenous cannabinoids, is a promising target to achieve this goal. In this issue of Neurogastroenterology and Motility, Fichna and colleagues report on a novel selective FAAH inhibitor, PF-3845, with potent antinociceptive and antidiarrheal effects in a mouse model. In this context, we briefly review the components of the ECS, discuss pharmacologic targets for indirect cannabinoid receptor stimulation, and describe recent research with cannabinoids for gut disorders.
Neurogastroenterology and Motility 04/2014; 26(4). DOI:10.1111/nmo.12329 · 3.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cannabinoids are used by patients with inflammatory bowel disease (IBD) to alleviate their symptoms. Little is known on patient motivation, benefit, or risks of this practice. Our aim was to assess the extent and motives for Cannabis use in patients with IBD and the beneficial and adverse effects associated with self-administration of Cannabis.
Consecutive patients with IBD (n = 313) seen in the University of Calgary from July 2008 to March 2009 completed a structured anonymous questionnaire covering motives, pattern of use, and subjective beneficial and adverse effects associated with self-administration of Cannabis. Subjects who had used Cannabis specifically for the treatment of IBD or its symptoms were compared with those who had not. Logistic regression analysis was used to identify variables predictive of poor IBD outcomes, specifically surgery or hospitalization for IBD.
Cannabis had been used by 17.6% of respondents specifically to relieve symptoms associated with their IBD, the majority by inhalational route (96.4%). Patients with IBD reported that Cannabis improved abdominal pain (83.9%), abdominal cramping (76.8%), joint pain (48.2%), and diarrhea (28.6%), although side effects were frequent. The use of Cannabis for more than 6 months at any time for IBD symptoms was a strong predictor of requiring surgery in patients with Crohn's disease (odds ratio = 5.03, 95% confidence interval = 1.45-17.46) after correcting for demographic factors, tobacco smoking status, time since IBD diagnosis, and biological use. Cannabis was not a predictor for hospitalization for IBD in the previous year.
Cannabis use is common in patients with IBD and subjectively improved pain and diarrheal symptoms. However, Cannabis use was associated with higher risk of surgery in patients with Crohn's disease. Patients using Cannabis should be cautioned about potential harm, until clinical trials evaluate efficacy and safety.
[Show abstract][Hide abstract] ABSTRACT: The stomach plays a critical role in digestion, processing ingested food mechanically and breaking it up into particles, which can be effectively and efficiently processed by the intestines. When the motility of the stomach is compromised, digestion is adversely affected. This can lead to a variety of disorders. Current diagnostic techniques for gastric motility disorders are seriously lacking, and are based more on eliminating other possibilities rather than on specific tests. Presently, gastric motility can be assessed by monitoring gastric emptying, food transit, intragastric pressures, etc. The associated tests are usually stationary and of relatively short duration. The present study proposes a new method of measuring gastric motility, utilizing the attenuation of an oscillator-induced electrical signal across the gastric tissue, which is modulated by gastric contractions. The induced high-frequency oscillator signal is generated within the stomach, and is picked up transluminally by cutaneous electrodes positioned on the abdominal area connected to a custom-designed data acquisition instrument. The proposed method was implemented in two different designs: first a transoral catheter was modified to emit the signal inside the stomach; and second, a gastric retentive pill was designed to emit the signal. Both implementations were applied in vivo on two mongrel dogs (25.50 kg and 25.75 kg). Gastric contractions were registered and quantitatively compared to recordings from force transducers sutured onto the serosa of the stomach. Gastric motility indices were calculated for each minute, with transluminal impedance measurements and the measurements from the force transducers showing statistically significant (p < 0.05) Pearson correlation coefficients (0.65 ± 0.08 for the catheter-based design and 0.77 ± 0.03 for the gastric retentive pill design). These results show that transcutaneous intraluminal impedance measurement has the potential with further research and development to become a useful diagnostic technique.
[Show abstract][Hide abstract] ABSTRACT: Esophageal lichen planus (LP) has been described as a cause of nonspecific esophagitis that may cause dysphagia, but its incidence is unknown. We aimed to estimate the incidence of esophageal LP in a defined geographic region and describe the clinical characteristics of affected patients.
A histopathology database for a population of 1 million people was searched for all esophageal mucosal biopsy results over an 8-year period. Cases showing inflammation or abnormalities without a diagnosis after three or more biopsies were reviewed for findings of LP.
Of 13,589 esophageal biopsies, only one received a diagnosis of LP. Seven patients (four male; mean age, 59 years; range, 39 to 76 years) were identified as having chronic dysphagia and nonspecific proximal esophagitis for which no diagnosis could be made. All patients had proximal inflammation, and six of seven had full-thickness lymphocytic infiltration. Elongation of the lamina propria papillae was noted in all patients, whereas six patients had parakeratosis and ballooning. Only one patient had findings potentially consistent with, but not sufficient for, a diagnosis of esophageal LP.
Esophageal LP appears to be extremely uncommon in this North American population, and esophageal biopsy alone is likely not sufficient to establish a diagnosis of LP.
Gut and liver 07/2013; 7(4):401-5. DOI:10.5009/gnl.2013.7.4.401 · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Capsule endoscopy is a noninvasive method for examining the small intestine. Recently, this method has been used to visualize the colon. However, the capsule often tumbles in the wider colon lumen, resulting in potentially missed pathology. In addition, the capsule does not have the ability to distend collapsed segments of the organ. Self-stabilizing capsule endoscopy is a new method of visualizing the colon without tumbling and with the ability to passively distend colon walls.
To quantitatively compare the detection rate of intraluminal suture marker lesions for colonoscopy by using a custom-modified, self-stabilizing capsule endoscope (SCE); an unmodified capsule endoscope (CE) of the same brand; and a standard colonoscope.
Four mongrel dogs underwent laparotomy and the implantation of 5 to 8 suture markers to approximate colon lesions. Each dog had both capsule endoscopy and self-stabilizing capsule endoscopy, administered consecutively in random order. In each case, the capsule was inserted endoscopically into the proximal lumen of the colon followed by pharmacologically induced colon peristalsis to propel it distally through the colon. Blinded standard colonoscopy was performed by an experienced gastroenterologist after the capsule endoscopies.
Experimental study in a live canine model.
Laparotomy, capsule endoscopy, colonoscopy.
Comparison of the marker detection rate of the SCE to that of the unmodified MiroCam CE and a colonoscope.
The average percentages of the marker detection rate for unmodified capsule endoscopy, self-stabilizing capsule endoscopy, and colonoscopy, respectively, were 31.1%, 86%, and 100% (P < .01), with both self-stabilizing capsule endoscopy and colonoscopy performing significantly better than the unmodified capsule endoscopy.
Acute canine model, suture markings poorly representative of epithelial polyps, limited number of animals.
The proposed self-stabilizing capsule endoscope delivered a significant improvement in detection rates of colon suture markings when compared with the unmodified capsule endoscope.
[Show abstract][Hide abstract] ABSTRACT: Background
Diabetic gastroparesis (DGP) is a gastric complication of diabetes mellitus that causes nausea, vomiting, early satiety, bloating and abdominal pain, in addition to significant morbidity.Sources of dataOriginal and review articles were reviewed through PubMed, including relevant guidelines from the European and American Neurogastroenterology Societies.Areas of agreementDiagnosis of DGP requires endoscopy and measurement of gastric emptying. Management requires prokinetic therapy, usually in addition to antinausea or other medications.Areas of controversyThe pathogenesis of DGP is poorly understood. Management strategies are highly variable.Growing pointsProkinetic and neuromodulatory medications are in human clinical trials specifically for gastroparesis.Areas timely for developing researchFurther understanding of the molecular pathology leading to DGP is required to potentially arrest the development of this serious diabetic complication. Evaluation of novel agents for use in DGP is sorely needed.
British Medical Bulletin 01/2013; 105(1). DOI:10.1093/bmb/ldt003 · 3.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Eosinophilic oesophagitis (EoE) has evolved from a supposedly rare entity to one whose incidence rates are approaching that of inflammatory bowel disease. The factors responsible for this apparent increase in the incidence remain obscure.
To assess various endoscopist and pathologist factors that might affect the frequency of EoE being detected in a well-defined North American population.
Increased endoscopist and pathologist awareness has contributed to the increased clinical recognition of EoE.
Cases of EoE were identified systematically using population-based pathology and endoscopy databases from January 2004 to December 2008 in Calgary, Canada (population 1.25 million). EoE frequency was estimated with time trend analysis. Characteristics of individual endoscopists (n = 45) were compared with diagnostic rates.
Crude population incidence of EoE increased from 2.1 per 10(5) in 2004 to 11.0 per 10(5) in 2008: an annual increase of 39% (P < 0.0001). The frequency in men was 4.5 times higher than in women (95% CI: 3.51-5.76). In patients presenting with dysphagia oesophageal biopsy rates increased from 17.0% in 2004 to 41.3% of EGDs in 2008: an annual rise of 26% (P < 0.0001). On multivariate regression analysis, those endoscopists with higher biopsy rates were more likely to make the diagnosis of EoE (P = 0.008). To include or exclude the diagnosis, typical histological features of EoE were reported more often by pathologists in 2008 as compared to 2004 (P = 0.01 & P < 0.0001 respectively).
The incidence of eosinophilic oesophagitis continues to rise in the general population, in part due to increasing oesophageal biopsy rates and a more detailed histological evaluation of specimens. The biopsy rate of an endoscopist is an indicator for a higher diagnostic yield.
[Show abstract][Hide abstract] ABSTRACT: To investigate the performance of a new software-based colonoscopy quality assessment system.
The software-based system employs a novel image processing algorithm which detects the levels of image clarity, withdrawal velocity, and level of the bowel preparation in a real-time fashion from live video signal. Threshold levels of image blurriness and the withdrawal velocity below which the visualization could be considered adequate have initially been determined arbitrarily by review of sample colonoscopy videos by two experienced endoscopists. Subsequently, an overall colonoscopy quality rating was computed based on the percentage of the withdrawal time with adequate visualization (scored 1-5; 1, when the percentage was 1%-20%; 2, when the percentage was 21%-40%, etc.). In order to test the proposed velocity and blurriness thresholds, screening colonoscopy withdrawal videos from a specialized ambulatory colon cancer screening center were collected, automatically processed and rated. Quality ratings on the withdrawal were compared to the insertion in the same patients. Then, 3 experienced endoscopists reviewed the collected videos in a blinded fashion and rated the overall quality of each withdrawal (scored 1-5; 1, poor; 3, average; 5, excellent) based on 3 major aspects: image quality, colon preparation, and withdrawal velocity. The automated quality ratings were compared to the averaged endoscopist quality ratings using Spearman correlation coefficient.
Fourteen screening colonoscopies were assessed. Adenomatous polyps were detected in 4/14 (29%) of the collected colonoscopy video samples. As a proof of concept, the Colometer software rated colonoscope withdrawal as having better visualization than the insertion in the 10 videos which did not have any polyps (average percent time with adequate visualization: 79% ± 5% for withdrawal and 50% ± 14% for insertion, P < 0.01). Withdrawal times during which no polyps were removed ranged from 4-12 min. The median quality rating from the automated system and the reviewers was 3.45 [interquartile range (IQR), 3.1-3.68] and 3.00 (IQR, 2.33-3.67) respectively for all colonoscopy video samples. The automated rating revealed a strong correlation with the reviewer's rating (ρ coefficient= 0.65, P = 0.01). There was good correlation of the automated overall quality rating and the mean endoscopist withdrawal speed rating (Spearman r coefficient= 0.59, P = 0.03). There was no correlation of automated overall quality rating with mean endoscopists image quality rating (Spearman r coefficient= 0.41, P = 0.15).
The results from a novel automated real-time colonoscopy quality feedback system strongly agreed with the endoscopists' quality assessments. Further study is required to validate this approach.
World Journal of Gastroenterology 08/2012; 18(32):4270-7. DOI:10.3748/wjg.v18.i32.4270 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Microscopic colitis (MC) is an umbrella term for collagenous colitis (CC) and lymphocytic colitis (LC). The incidence of these diseases is increasing for unclear reasons.
To identify factors that may impact diagnosis rates of MC in a North American population.
Population-based pathology and endoscopy databases were searched to identify all cases of MC and the number of lower endoscopy (LE) procedures performed over a five-year period (January 2004 to December 2008) in a catchment area of 1.2 million people. Endoscopist characteristics were compared with diagnostic rates.
MC incidence increased from 1.68 per 10,000 in 2004, to 2.68 per 10,000 in 2008, with an average annual increase of 12% per year (95% CI 7% to 16%; P<0.0001). The incidence rate of LC increased but the rate of CC remained stable over the study period. Approximately one-half of the cases were probable and one-half were definite based on pathologists' reports - a proportion that remained stable over time. The number of LEs per population increased by 4.6% annually over the study period (95% CI 2.8% to 6.4%; P<0.0001), and biopsy rates in LE for MC indications (eg, unexplained diarrhea, altered bowel habits) increased over time (3.4% annual increase [95% CI 1.8% to 6.0%]; P<0.001). Endoscopists with an academic practice, gastroenterologists and those with lower annual endoscopy volumes were more likely to make a diagnosis of MC.
The incidence of MC is rising due to increased diagnosis of LC, while CC incidence remains stable. Patients with MC symptoms have stable endoscopy rates but are being biopsied more often. Physician training, practice type and endoscopy volume impact the diagnostic rates of MC.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 08/2012; 26(8):515-20. · 1.98 Impact Factor