Parietal cell protrusions (PCP) in gastric ulcer disease.
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Anti-Ulcer Agents↗
Biomedical subjects
G Tougas
Publications and source records attributed to G Tougas.
Cortical evoked responses following esophageal balloon distension and electrical stimulation in healthy volunteers.
Recording of evoked potential responses represents an objective and quantifiable method to study visceral afferent sensory pathways in humans. We examined the evoked responses to mechanical distension (balloon) and electrical stimulation of the proximal and distal esophagus. A standard manometric catheter with a latex balloon and an additional electrode attached to its body was placed in the lower esophagus in 15 healthy young volunteers. Repeated nonpainful balloon distension stimuli above the individual sensation threshold (0.17 Hz, 12-20 ml) or short electrical impulses (0.2 Hz, 12-16 mA) were delivered in an alternate fashion at 23 and 33 cm from the nares. Evoked potential responses (EP) were recorded through 22 scalp surface electrodes using the standard 10/20 International EEG system of electrode placement. Balloon distension produced a reproducible triphasic response at both sites. Peak latencies of three negative EP peaks were 92+/-17, 229+/-40, and 339+/-36 msec with proximal stimulation versus 154+/-24, 275+/-24, and 384+/-30 msec obtained with distal stimulation (P < 0.001). Electrical stimulation produced a triphasic response with significantly shorter peak latencies at both sites when compared to mechanical stimulation (P < 0.001). Peak latencies were 74+/-12, 137+/-11, and 245+/-27 msec proximal versus 83+/-12, 148+/-32, and 247+/-51 msec with distal stimulation (P < 0.01). The calculated conduction velocities for both modes of stimulation (balloon: 1.73+/-0.9 m/sec vs electrical: 10.1+/-3.4 m/sec) are compatible with conduction through C fibers and Adelta fibers, respectively. Both modes of stimulation produce characteristic brain responses that are conveyed through different types of afferent fibers. The respective contributions of both types of fibers to esophageal function and symptomatology can be specifically addressed using this approach in both normal and pathologic conditions.
Adult↗
Assessment of afferent gut--brain function using cerebral evoked responses to esophageal stimulation.
Increasing awareness is attributed to altered sensory perception in the pathogenesis of gastrointestinal disorders. Evoked potentials (EP), which represent the brain's electrical response to peripheral stimulation, have recently been used to investigate where and how (GI) afferent information is processed along the brain-gut axis. EP can be obtained with electrical stimulation or balloon distention in the esophagus in humans. Stimulation of afferent neural pathways in the esophagus produces cerebral evoked responses allowing assessment of the peripheral afferent neural pathways involved, and of the function of integrative neural centers within the brain. Recent studies using esophageal EP indicate that the cerebral response to either mode of stimulation depends on the perception of the stimuli. Using electrical stimulation, a clear dose-response relationship is found. The EP response obtained with electrical stimulation is in keeping with those recorded using direct cervical stimulation of the vagus nerve, supporting evidence that esophageal EP are produced by activation of afferent vagal pathways. From the conduction velocity of the autonomic (vagal) nerves conveying information from esophagus to brain, it was concluded that non-painful electrical stimuli predominantly activate fast conducting myelinated afferent sensory fibers (A-fibers), while EP to balloon distention are largely due to activation of unmyelinated C-fibers. Techniques, however, vary widely amongst different investigators, and some electrophysiological parameters remain controversial, as there is no standard approach. Using balloon distention, EP waveforms vary widely between laboratories, suggesting that EP are substantially influenced by the stimulator devices (pump, respirator). EP to balloon distention are hampered by a relatively low signal-to-noise ratio (SNR), which is probably due to long inflation-deflation time (> 200 ms). With electrical stimulation, there is much less variability between different groups, and SNR is distinctly higher. This method appears to be most attractive for studies of afferent esophageal function. Standardization of the techniques is important, before esophageal EP can be regarded as a useful diagnostic approach in patient groups.
Afferent Pathways↗
Assessment of the visceral afferent and autonomic pathways in response to esophageal stimulation in control subjects and in patients with diabetes.
OBJECTIVE: To examine the effects of esophageal stimulation on vagal afferent and efferent pathways in volunteers without diabetes and patients with diabetes. DESIGN: Prospective physiological study. PARTICIPANTS: Fourteen control subjects without diabetes and 6 patients with diabetes. INTERVENTIONS: Electrical and mechanical stimulation of the esophagus. OUTCOME MEASURES: Cortical evoked potentials and the power spectra of heart rate variability. RESULTS: For the control subjects, there was a significant decrease in the ratio of the low frequency to high frequency (LF:HF) power (i.e., increased vagal efferent modulation) during stimulation. Reproducible cortical evoked potentials were obtained from all control subjects. In the 6 patients with diabetes, who had viscerosensory and autonomic neuropathy, the cortical evoked potentials showed an erratic non-reproducible response to electrical esophageal stimulation; however, the LF:HF ratio decreased in these patients during stimulation, suggesting an intact subcortical reflex circuit. CONCLUSIONS: Vago-afferent fibres can be studied using minimally invasive techniques, and the power spectral analysis of heart rate variability permits study of autonomic vago-efferent pathways.
Adolescent↗
Estimation of habituation and signal-to-noise ratio of cortical evoked potentials to oesophageal electrical and mechanical stimulation.
Electrical and mechanical stimulation of the oesophagus has been recently proposed to examine the physiological effects of autonomic stimulation in humans. Cortical evoked potentials (EPs) to oesophageal stimulation provide an assessment of afferent fibres and central processing. However, habituation takes place during averaging of cortical EPs and reduces the signal-to-noise ratio (SNR) as the number of stimuli increases. The SNR of cortical EPs to oesophageal stimulation is computed for 15 normal subjects. Habituation is characterised by the Euclidean distance between the EEG response to single stimuli and the averaged EP, to serve as an objective measure of similarity between the averaged EP and the single-stimulus EEG. With electrical stimulation, the SNR is highest (0.41 +/- 0.21) for 1-12 stimuli and then significantly decreases to 0.2 +/- 0.08 for 13-24 stimuli (p < 0.001). With balloon distension (BD), the SNR is highest (0.22 +/- 0.16) for 1-12 stimuli and lowest (0.12 +/- 0.14) for 13-24 stimuli, but these SNRs are not significantly different from each other. Both electrical and mechanical stimulation of the oesophagus produce rapidly adapting EPs. The SNR of the EPs is higher with electrical stimulation than with BD. The EPs response to BD has a higher variability and is more noisy. Consequently, these results suggest that the overall cortical EP response to electrical stimulation of the oesophagus is more reproducible than that due to balloon distension.
Adult↗
The magnitude of the central response to esophageal electrical stimulation is intensity dependent.
BACKGROUND & AIMS: Cerebral evoked potential (EP) responses to visceral stimulation represent a powerful method to assess visceral afferent pathways. The aim of this study was to establish basic stimulation parameters (dose-response relationship in EP amplitude and topographic brain organization) during electrical esophageal stimulation. METHODS: Electrical esophageal stimulation was performed in repeated series of 24 stimuli in 15 healthy subjects (25 years) by steps of 5 mA, ranging from 0.5 mA (sham) to 25 mA. EPs were obtained using scalp electrodes positioned according to the 10/20 International electroencephalographic system. Topographic EP maps were created using interpolation techniques. RESULTS: No cerebral responses were recorded with sham stimulation. A significant intensity-dependent increase of the major EP peaks (N1-P2) was observed between 5 and 25 mA (P < 0.05). A significant shortening of the mean peak latency of the first peak (N1) occurred with increasing stimulus intensity (P < 0.0001). Topographic brain maps localized the early EP peaks centrally, whereas later peaks were spread symmetrically over the centroparietal region. CONCLUSIONS: The clear dose-response relationship in the brain response with increasing stimulus intensities probably reflects increased recruitment of afferent fibers. Early peaks originate from deep central brain structures, whereas later peaks are localized exclusively in cortical regions.
Adult↗
Botulinum toxin use in pediatric esophageal achalasia: a case report.
Esophageal achalasia (EA) has been historically treated by esophageal dilatation or myotomy with or without fundoplication. Botulinum toxin (Botox-Allergan) use in pediatric EA has not been previously described. The authors' objective was to observe the efficacy of botulinum toxin injection into the lower esophageal sphincter (LES) for EA. An 11-year-old boy presented with a 9-month history of frequent pneumonia, productive cough, and a 1-year history of chest discomfort and odynophagia. Chest radiograph showed changes compatible with aspiration. Upper gastrointestinal (UGI) series showed typical narrowing of the LES, and 24-hour pH study showed no reflux. Esophageal manometry showed classic findings of achalasia. An upper gastrointestinal endoscopy was performed showing a huge volume of retained food. A direct four-quadrant injection was performed with a total of 100 U of botulinum toxin into the LES. UGI series showed improvement in esophageal emptying. Esophageal manometry showed impressive improvement in LES pressure (preinjection, 44.1 mm Hg to postinjection mean of 16.6 mm Hg), percent relaxation (preinjection, 30% to postinjection, 58.8%), and duration of relaxation (preinjection, 1.9 seconds to postinjection, 11 seconds). The patient has not had any further respiratory symptoms, chest pain, or odynophagia in 8 months of follow-up. Botulinum toxin injection is simple and effective for EA and merits its study in a prospective manner in the pediatric population.
Botulinum Toxins↗
Modulation of neurocardiac function by oesophageal stimulation in humans.
1. The heart and the oesophagus have similar sensory pathways, and sensations originating from the oesophagus are often difficult to differentiate from those of cardiac origin. We hypothesized that oesophageal sensory stimuli could alter neurocardiac function through autonomic reflexes elicited by these oesophageal stimuli. In the present study, we examined the neurocardiac response to oesophageal stimulation and the effects of electrical and mechanical oesophageal stimulation on the power spectrum of beat-to-beat heart rate variability in male volunteers. 2. In 14 healthy volunteers, beat-to-beat heart rate variability was compared at rest and during oesophageal stimulation, using either electrical (200 microns, 16 mA, 0.2 Hz) or mechanical (0.5 s, 14 ml, 0.2 Hz) stimuli. The power spectrum of beat-to-beat heart rate variability was obtained and its low- and high-frequency components were determined. 3. Distal oesophageal stimulation decreased heart rate slightly (both electrical and mechanical) (P < 0.005), and markedly altered heart rate variability (P < 0.001). Both electrical and mechanical oesophageal stimulation increased the absolute and normalized area of the high-frequency band within the power spectrum (P < 0.001), while simultaneously decreasing the low-frequency power (P < 0.005). 4. In humans, oesophageal stimulation, whether electrical or mechanical, appears to amplify respiratory-driven cardiac vagoafferent modulation while decreasing sympathetic modulation. The technique provides access to vagoafferent fibres and thus may yield useful information on the autonomic effects of visceral or oesophageal sensory stimulation.
Adolescent↗
The cerebral response to electrical stimuli in the oesophagus is altered by increasing stimulus frequencies.
Recording of cerebral evoked responses (EP) allows the assessment of visceral afferent pathways and gut-brain communication, but the optimal stimulation parameters remain to be established. The present study determined the optimal stimulation frequency of electrical stimulation of the oesophagus to elicit EP responses. In 13 healthy male volunteers (24.1 +/- 5.9 years), a 5 mm stainless-steel electrode was placed in the distal oesophagus for electrical stimulation (ES). EP were recorded from 21 scalp electrodes placed according to the 10/20 International system. ES (15 mA, 200 microseconds) were delivered in repeated series of 24 stimuli. Stimulus frequency was randomly altered in different series using a pseudologarithmic range (0.1, 0.2, 0.3, 0.5, and 1 Hz). Two series of stimuli were applied using each stimulation frequency. Two-dimensional topographic brain maps were created using interpolation techniques at each stimulation frequency. With increasing stimulus frequency, a significant and progressive decrease of EP amplitudes was observed between frequencies of 0.1 Hz and 1.0 Hz (P1/N2: 7.6 +/- 1.2 vs 1.4 +/- 0.3* microV, N2/P2: 17.2 +/- 1.7 vs 4.6 +/- 0.4* microV, P2/N3: 6.9 +/- 0.7 vs 4.2 +/- 0.5* microV; * = P < 0.05). In addition, there was a significant shortening of the mean peak latency of the intercalated P2 peak (P < 0.0005), with a similar trend for the P3 peak (P < 0.06), with increasing stimulus frequency from 0.1-1.0 Hz. Topographic brain maps localized the maximal early peaks (N1,P1.N2) in the paracentral cortical region (C3, Cz, C4), whereas the later peaks (P2 to P3) were symmetrically spread over the centroparietal and temporal regions (Cz, Pz, T5, T4). There was no difference in the cortical location of maximal EP amplitudes with increasing stimulus frequency. In conclusion, there is a clear relationship between stimulus frequency and amplitude of EP, suggesting rapid attenuation of the cerebral autonomic neural responses with increased electrical stimulation frequency. The effect of increased frequency on peak latencies suggests an alteration of stimulus processing in the thalamocortical region due to an altered perception of stimuli. Early EP peaks originate from basal structures of primarily the dominant hemisphere, while later peaks are localized in centroparietal cortical regions.
Adult↗
Neurocardiac response to esophageal electric stimulation in humans: effects of varying stimulation frequencies.
The purpose of this study was to determine if the cardioautonomic responses to esophageal electric stimulation were mediated entirely through modulation of respiratory frequency or a direct vagal effect. We performed electric stimulation of the esophagus in 13 healthy male controls (24 +/- 6 yr) using a manometric catheter to which a stainless steel electrode was attached. Stimulation frequencies ranged from 0.1 to 1 Hz and were applied in random fashion. We computed the power spectra of the heart rate variability and respiratory frequency as measures of autonomic function. Electric stimulation of the esophagus produced significant increases in the high-frequency power of the heart rate autospectrum at all stimulation frequencies (maximal at 0.2 Hz). However, regardless of the frequency of esophageal stimulation, the respiratory rate was not changed from baseline. These studies indicate that enhancement of cardiac vagal modulation observed in response to esophageal electric stimulation is not primarily due to changes in respiratory frequency, but rather occurs through a direct, vagally mediated action through sensory neural pathways involving vagal esophageal afferents.
Adult↗
Motility in irritable-bowel syndrome.
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Colonic Diseases, Functional↗
Efficacy of H2 receptor antagonists in the treatment of gastroesophageal reflux disease and its symptoms.
Gastroesophageal reflux disease (GERD) is caused by prolonged esophageal mucosal exposure to acid gastric refluxate due to failure of the normal antireflux mechanisms of the lower esophageal sphincter. Gastroesophageal reflux can be controlled by suppression of acid secretion or by improvement of gastric emptying and esophageal clearance. H2 receptor antagonists are the most commonly used antisecretory drugs, and in the past 20 years have constituted the cornerstone of therapy for the treatment of reflux disease. They have been shown to be effective in the symptomatic treatment of intermittent or mild nonerosive GERD (greater than 70%). When used at the usual recommended dose, all four H2 receptor antagonists (cimetidine, ranitidine, famotidine and nizatidine) are equally effective and are found to be generally very safe; interactions with other drugs metabolized through the cytochrome p450 notwithstanding. However, their efficacy is limited in more severe forms of GERD such as erosive esophagitis (symptomatic improvement 40% to 60%, endoscopic healing 40% to 50%) in which the superior efficacy and more rapid symptomatic relief provided by proton pump inhibitors is clearly demonstrated. The availability of H2 receptor antagonists for over-the-counter use will increase their use for mild and intermittent disease but is unlikely to alter the need for more potent acid suppression in aggressive reflux disease.
Gastroesophageal Reflux↗
Cerebral evoked responses to gastrointestinal stimulation in humans.
Recent advances have permitted recording of evoked potentials (EPs) in response to electrical and mechanical stimulation of the gastrointestinal (GI) organs via methods used primarily in clinical neurophysiology. Current research involving stimulation of the esophagus, rectum, and colon, and recording the corresponding responses on the scalp, is being practiced in only a few laboratories. This review examines the engineering aspects of recording EPs, such as characteristics of the stimuli, placement of stimulus electrodes in the GI tract, and enhancement of evoked potential signals. We also discuss the physiological concepts involved in the generation of EPs, and how these compare with somatosensory evoked responses. Current experimental techniques employed by various investigators and results reported from their laboratories are compared. We believe that cerebral EPs to GI stimulation could be useful in studying a number of pathophysiological conditions such as gastroesophageal reflux disease, diffuse esophageal spasm, chronic inflammatory bowel disorders, chronic abdominal pain, and irritable bowel syndrome, among others. We hope that the present review will generate interest in the use of EPs arising out of GI stimulation, aiding in understanding their physiological implications in healthy subjects and in GI disorders.
Cerebral Cortex↗
Impaired gastric emptying in mechanically ventilated, critically ill patients.
OBJECTIVE: To measure gastric emptying in critically ill patients using an acetaminophen absorption model and determine which variables are associated with impaired gastric emptying. DESIGN: A prospective, cohort study. SETTING: A medical/surgical ICU at a tertiary care hospital: Hamilton General Hospital, Hamilton, Ontario. PATIENTS AND PARTICIPANTS: We recruited 72 mechanically ventilated patients expected to remain in the ICU for more than 48 h. Our results were compared to those in healthy volunteers. INTERVENTION: Within 48 h of admission to the ICU, 1.6 g acetaminophen suspension were administered via a nasogastric tube into the stomach. Blood samples were drawn a t = 0, 30, 60, 90, and 120 min for measurement of plasma acetaminophen levels determined by the enzymatic degradation method. MEASUREMENTS AND RESULTS: Maximal concentration of acetaminophen was 94.1 (75.3) mumol/l compared to 208.4 (33.1) mumol/l in a control population (p < 0.0001). The time to reach the maximal concentration was 105 min (60-180) compared to 30 min (15-90) in controls (p < 0.0001). The area under the time-acetaminophen concentration curve t = 120 was 9301 (7343) mumol/min per l compared to 11644 (1336) mumol/min per l in the controls (p = 0.28). The variables associated with delayed gastric emptying were age, sex and use of opioids for analgesia and sedation. CONCLUSIONS: Gastric emptying is delayed in critically ill patients. The important consequences of this phenomenon include intolerance to enteral nutrition and gastric colonization. Strategies to minimize the use of narcotics may improve gastric emptying. Studies to examine the effect of gastrointestinal prokinetic agents on gastric emptying are needed.
Acetaminophen↗
Omeprazole produces parietal cell hypertrophy and hyperplasia in humans.
While there is evidence that omeprazole may induce changes in parietal cells, the effect of acid suppression on parietal cells in humans is poorly documented. This study was undertaken to evaluate the effects of omeprazole in human parietal cells over time. The light microscopic morphology of parietal cells in gastric biopsies from 17 patients on omeprazole were compared with those from 13 patients on ranitidine and 20 patients on no acid-lowering medication. Light microscopic and ultrastructural morphology of parietal cells was also evaluated in an additional 14 patients before and after omeprazole administration. Objective measurements of parietal cell height, mass and number were analyzed using analyses of variance. Electron microscopy was used to evaluate parietal cell enlargement. Twenty-five of 31 biopsies from patients on omeprazole, 1 of 13 from patients on ranitidine, and 0 of 20 from patients on neither drug showed parietal cell enlargement. Parietal cell height, mass, and number were increased in omeprazole-treated patients compared with ranitidine-treated patients and those on neither drug, and with the group also evaluated prior to beginning omeprazole treatment. Parietal cell height and mass were increased in patients on omeprazole longer than 12 months compared with biopsies from patients on the drug for less than 12 months. Resin-embedded sections and electron microscopy showed enlarged parietal cells with prominence of cytoplasmic tubulovesicles with sparse secretory canaliculi. Parietal cell hypertrophy and hyperplasia develops in patients on chronic omeprazole therapy; this can be recognized on routine examination of histologic sections. These morphologic changes increase with duration of therapy.
Adolescent↗
Cisapride improves gastric emptying in mechanically ventilated, critically ill patients. A randomized, double-blind trial.
We conducted a randomized, double-blind, placebo-controlled trial in mechanically ventilated intensive care unit (ICU) patients to evaluate the effect of cisapride on gastric emptying using an acetaminophen absorption model. We enrolled 72 patients expected to remain in the ICU for more than 48 h; 39% were female; the average age was 54.0 +/- 19.1 yr; 47% were postoperative, 83% were receiving narcotics, and the mean simplified acute physiology score (SAPS) was 9.5 +/- 3.0. Within 72 h of admission to ICU, 1.6 g of acetaminophen suspension was administered via a nasogastric tube into the stomach (Day 1). Blood samples were drawn at baseline, 30, 60, 90, 120, and 180 min for measurement of plasma acetaminophen levels. The following morning (Day 2), patients were randomized to receive 20 mg of cisapride or placebo and gastric emptying was again assessed. The difference (Day 2-Day 1) in the maximal plasma concentration was 49.1 mumol/L in the cisapride groups compared with 12.3 mumol/L in the placebo group (p = 0.005) and the time to reach maximal concentration was significantly shorter in the cisapride group (-40.8 min versus -4.2 min, p = 0.02). The difference in area under the time-acetaminophen concentration curve was also greater in the patients receiving cisapride (5,534 versus 2,832, p = 0.09). We conclude that cisapride enhances gastric emptying in critically ill patients. Studies to examine the effect of cisapride on tolerance to enteral nutrition, infectious morbidity, and other clinically important outcomes are warranted.
Acetaminophen↗
Integration of vagal afferent responses to duodenal loads and exogenous CCK in rats.
The neurophysiological responses to 0.1 ml duodenal balloon inflation, 0.5 ml duodenal loads of normal saline, and 100 pmol close celiac arterial infusions of cholecystokinin (CCK) were obtained from 14 left cervical vagal afferent fibers in 14 rats. Duodenal, but not gastric, loads increased discharge rates in these slowly adapting fibers. CCK alone excited these fibers, and CCK pretreatment amplified subsequent duodenal load responses. Furthermore, duodenal loads generated greater responses when combined with CCK infusions. The small (< 3 mm) receptive fields of these fibers were localized to the ventral wall of the proximal duodenum, with C fiber conduction velocities (< 2 m/s). These results demonstrate for the first time rat duodenal load-sensitive vagal afferents. They can integrate signals arising from CCK and duodenal loads, and may mediate aspects of the role of CCK in the inhibition of gastric emptying and the control of food intake.
Afferent Pathways↗
Relation of acupuncture and vagal gastric acid secretion.
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Acupuncture Therapy↗