Long-term effects of omeprazole on the gastric mucosa.
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Anti-Ulcer Agents↗
Biomedical subjects
G Tougas
Publications and source records attributed to G Tougas.
Upper gastrointestinal symptoms in North America: prevalence and relationship to healthcare utilization and quality of life.
The aim of this study was to determine the prevalence of upper gastrointestinal symptoms (UGIS) in a general population and quantify the relationship of those symptoms to healthcare utilization and quality of life. In-person interviews were conducted with 2056 United States and Canadian residents selected at random. Subjects reported frequency and severity for 11 symptoms, prescription and over-the-counter medication use, primary care and specialty physician visits in prior three months, and completed the Psychological General Well-Being Scale. For analyses, subjects were classified into four mutually exclusive symptom groups: gastroesophageal reflux disease (GERD) -like, GERD plus motility-like (GERD+), ulcerlike, and motility-like. Of the total sample, 51.4% reported the occurrence of at least one UGIS in the prior three months. Subjects in the GERD+ and ulcer groups used more prescription medications and were more likely to see a physician about the symptoms (P<0.001). Subjects with symptoms demonstrated poorer quality of life compared to subjects with no symptoms. The prevalence of UGIS in the general population is high and symptoms are associated with significant health-care utilization and poorer quality of life.
Adult↗
Determinants of occurrence and volume of transpyloric flow during gastric emptying of liquids in dogs: importance of vagal input.
The precise factors and their relative contributions that lead to individual flow pulses across the pylorus during liquid gastric emptying remain unclear. Our objective was to determine the factors leading to individual flow pulses, their relative contributions and the role of the vagus nerve in their modulation. Proximal gastric tone had a strong positive correlation with the volume of the corresponding transpyloric flow pulse whereas pyloric tone had an inverse correlation. Antral contractions were associated with the presence but not the volume of the pulse. Acute vagal blockade retarded emptying via loss of proximal gastric tone and increased outflow resistance and loss of propagating antral pressure waves. In conclusion, the major determinants of the volume of pulsatile transpyloric flow are proximal gastric and pyloric tone. The vagus nerve plays a key role in regulating both proximal gastric and pyloric tone as well as moderating propagating antral contractions.
Animals↗
Nitrergic and cholinergic vagal pathways involved in the regulation of canine proximal gastric tone: an in vivo study.
To better understand the relationship between cholinergic and nitrergic (NO) innervation in the regulation of proximal gastric (fundic) tone in vivo, the effects of nitric oxide synthase blockade on fundic tone were studied in conscious dogs using vagal cooling and an electronic barostat. Vagal cooling, atropine (0.05 mg kg-1 i. v. bolus) and hexamethonium (1 mg kg-1 i.v. bolus) all markedly decreased fundic tone as reflected by increased intragastric volume, indicating a significant contribution of vagal and enteric cholinergic pathways to the maintenance of canine fundic tone. Administration of L-NNA (10 mg kg-1 i.v. bolus) increased fundic tone and the effects of L-NNA were completely prevented by prior vagal cooling or atropine administration, but not by pretreatment with hexamethonium. The relaxation effects of neurally derived NO appear primarily related to inhibition of ongoing vagal cholinergic activity. The data are consistent with the primary site of action of nitrergic mechanisms on gastric fundic tone in conscious dogs being at a presynaptic site on vagal cholinergic efferent nerves.
Animals↗
Abnormal cerebral processing of oesophageal stimuli in patients with noncardiac chest pain (NCCP).
In noncardiac chest pain (NCCP), altered visceral perception may result from abnormal cerebral processing of sensory input rather than abnormalities of afferent pathways. However, the interactions between symptoms, autonomic function and oesophageal stimuli are poorly studied. Oesophageal stimulation elicits reproducible cortical evoked potentials [CEP] and modulates heart rate variability via vagal pathways, as visible on power spectrum analysis of heart rate variability [PS-HRV]. These methods are increasingly used to study the function of visceral afferent neural pathways in human. The aim of this study was to compare EP and PS-HRV during oesophageal stimuli in NCCP and controls. Twelve healthy volunteers (one female, 11 male; aged 24-51 years; mean 32 +/- 8 years), and eight NCCP patients (three female, five male; age range 26-58, mean 40.5 +/- 10 years) were studied. Electrical oesophageal stimulation (EOS; 200 microseconds, 0.2 Hz, 25 stimuli) was applied to the oesophageal wall 5 cm above the lower oesophageal sphincter (LOS), and perception thresholds (measured in mA) determined. EP responses were recorded using 22 standard electroencephalogram scalp electrodes. Autonomic activity was assessed using PS-HRV, before, during, and after oesophageal stimulation. Measured PS-HRV indices included high frequency (HF; 0. 15-0.5 Hz) and low frequency (LF; 0.06-0.15 Hz) power, respectively, assessing vagal and sympathetic activity, and the LF/HF ratio. EOS perception occurred at lower thresholds in NCCP than in controls (3. 6 +/- 1 vs. 7.8 +/- 2 mA, P < 0.05). EP amplitude was greater (13 +/- 2 vs. 6 +/- 1 microV, P < 0.0001), and latency longer in controls vs. NCCP (191 +/- 7 ms vs. 219 +/- 6 ms, P < 0.001). In NCCP, EOS decreased sympathetic outflow (low frequency peak on PS-HRV) and increased cardiovagal activity (high frequency peak, P < 0.02) to a significantly higher degree in comparison with controls. During EOS, heart rate decreased in NCCP from 68 vs. 62 beats min-1 (P < 0.003) but not in controls. In NCCP patients, EOS was perceived at lower intensities and was associated with a greater cardiovagal reflex response. EP responses associated with EOS were smaller in NCCP than in controls, suggesting that an increased perception of oesophageal stimuli results from an enhanced cerebral processing of visceral sensory input in NCCP, rather than from hyperalgesic responses in visceral afferent pathways.
Adult↗
Standardization of a simplified scintigraphic methodology for the assessment of gastric emptying in a multicenter setting.
OBJECTIVE: Scintigraphy remains the gold standard to study gastric emptying. The technique is onerous and normal values vary between centers. Standardized protocols, although desirable, are not presently available. We validated a simplified scintigraphic protocol in a multicenter setting. METHODS: In 69 healthy volunteers from seven Canadian institutions, gastric emptying of a standard meal (99mTc-labeled beef liver) was assessed by scintigraphy every 10 min for 1 h, then every 20 min for the next 2 h. Gastric retention was fitted to a power exponential model, Prop(t) = (-(kappat)beta) with Prop(t) = proportion of retention at time t, either using all 13 time intervals (conventional technique) or using measurements at 0, 1, 2, and 3 h (simplified technique). RESULTS: The power exponential model yielded identical emptying curves and T 1/2 values with both techniques. Gastric emptying was more rapid in men than in women < 35 yr (p<0.01) and in younger than in older men (p<0.005). Gastric emptying was slower in women from Québec than in women from Ontario (p<0.04). Gastric retention was similar at 1, 2, and 3 h among the seven centers. Gastric emptying of a beef liver meal was slower than that of a low fat egg substitute (p<0.03). CONCLUSIONS: A simpler scintigraphic approach, using four rather than 13 samples, provides results comparable to those of the conventional technique. This simpler approach provides an economical, yet accurate, alternative to the techniques presently used and is applicable to a multicenter setting.
Adult↗
Assessment of gastric emptying using a low fat meal: establishment of international control values.
OBJECTIVE: The diagnosis of gastroparesis implies delayed gastric emptying. The diagnostic gold standard is scintigraphy, but techniques and measured endpoints vary widely among institutions. In this study, a simplified scintigraphic measurement of gastric emptying was compared to conventional gastric scintigraphic techniques and normal gastric emptying values defined in healthy subjects. METHODS: In 123 volunteers (aged 19-73 yr, 60 women and 63 men) from 11 centers, scintigraphy was used to assess gastric emptying of a 99Tc-labeled low fat meal (egg substitute) and percent intragastric residual contents 60, 120, and 240 min after completion of the meal. In 42 subjects, additional measurements were taken every 10 min for 1 h. In 20 subjects, gastric emptying of a 99Tc-labeled liver meal was compared with that of the 99Tc-labeled low fat meal. RESULTS: Median values (95th percentile) for percent gastric retention at 60, 120, and 240 min were 69% (90%), 24% (60%) and 1.2% (10%) respectively. A power exponential model yielded similar emptying curves and estimated T50 when using images only taken at 1, 2 and 4 h, or with imaging taken every 10 min. Gastric emptying was initially more rapid in men but was comparable in men and women at 4 h; it was faster in older subjects (p < 0.05) but was independent of body mass index. CONCLUSIONS: This multicenter study provides gastric emptying values in healthy subjects based on data obtained using a large sample size and consistent meal and methodology. Gastric retention of >10% at 4 h is indicative of delayed emptying, a value comparable to those provided by more intensive scanning approaches. Gastric emptying of a low fat meal is initially faster in men but is comparable in women at 4 h; it is also faster in older individuals but is independent of body mass.
Adult↗
The autonomic nervous system in functional bowel disorders.
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Autonomic Nervous System Diseases↗
Effects of esophageal stimulation in healthy subjects.
We studied the effects of esophageal electrical stimulation on heart rate variability power spectra (PS/HRV) and cortical evoked potentials (EPs) in healthy subjects. The intensity of stimulation was varied from 2.7 to 20 mA. We found that the amplitude of the cortical evoked potentials (amplitude of the N2/P2 peak) increased from 5.1 +/- 0.7 microV at 5 mA to 16.3 +/- 1.1 microV at 20 mA. The PS/HRV showed an increase in the vagal modulation of the sinus node. When the stimulation frequency was varied from 0.1 to 1 Hz at a constant intensity of 15 mA, the amplitude of cortical EPs (N2/P2 peak) decreased with increase in the frequency of stimulation (p < 0.05). The LF:HF ratio decreased significantly for all frequencies of stimulation (p < 0.005). An experimental paradigm to evoke the cognitive component in the cortical EPs yielded a peak around 354 ms following the stimulus.
Cerebral Cortex↗
Effects of esophageal stimulation in patients with functional disorders of the gastrointestinal tract.
We studied the effects of esophageal electrical stimulation on cortical-evoked potentials (EPs) and power spectrum of heart rate variability (PS/HRV) in patients with diabetes and non-cardiac chest pain (NCCP). We also recorded cognitive-evoked potentials (P300 EPs) in response to an odd-ball stimulation in patients with NCCP. Diabetic patients did not yield reproducible cortical EPs. Their power spectra of heart rate variability (PS/HRV) showed an increased vagal modulation during stimulation. In patients with NCCP the P300 EPs were of greater amplitude (17 +/- 3 microV vs. 12 +/- 1 microV in controls, p < 0.04), while peak latencies were slightly elongated in patients (382 +/- 22 ms vs. 354 +/- 12 ms in controls). The PS/HRV in these patients also showed an increased vagal modulation of the sinus node activity. Our results suggest the following: (1) in patients with diabetes, afferent pathways and processing of sensory signals are likely to be impaired; (2) an increased perception of esophageal stimulation reflects an exaggerated brainstem response and altered cortical processing of visceral sensation in patients with NCCP.
Adolescent↗
Lack of effect of spearmint on lower oesophageal sphincter function and acid reflux in healthy volunteers.
BACKGROUND: Spearmint is commonly used as an antispasmodic and as a flavouring in several medications including antacids. It can produce heartburn, presumably by lowering lower oesophageal sphincter (LES) tone, but the mechanism has not previously been objectively examined. AIM: To study the effect of spearmint on LES function, acid reflux and symptoms. METHODS: In healthy volunteers, a Dent Sleeve and a pH electrode were placed in the distal oesophagus. They were then given spearmint either in a flavouring (0.5 mg), or a high (500 mg) dose, or a placebo, using a double-blind randomized crossover design. LES pressure, oesophageal pH and symptoms were recorded for 30 min before and after administration. RESULTS: LES pressure was not affected by spearmint, either high dose (19.6 vs. 16.0 mmHg), flavouring dose (20.2 vs. 19.8 mmHg) or placebo (20.5 vs. 19.2 mmHg, all N.S.). There were no differences in reflux occurrence following high dose (mean = 0.65 vs. 0.85 episodes), low dose (0.4 vs. 0.5 episodes) or placebo (0.7 vs. 1.10 episodes, all N.S.). There was a significant increase in mean symptom scores following high-dose spearmint (0 vs. 0.35, P = 0.03), but not low dose (0 vs. 0.2) or placebo (0 vs. 0.5, both N.S.). One subject reported symptoms with placebo, one with low dose, and six with high dose; all without increased reflux episodes or decreased sphincter pressure. CONCLUSION: Spearmint has no effect on LES pressure or acid reflux. Flavouring doses of spearmint do not produce more symptoms than placebo while high doses can be associated with symptoms, presumably from direct mucosal irritation but not reflux.
Adolescent↗
Cognitive evoked potentials to anticipated oesophageal stimulus in humans: quantitative assessment of the cognitive aspects of visceral perception.
Evoked potential studies provide an objective measure of the neural pathways involved with perception. The effects of cognitive factors, such as anticipation or awareness, on evoked potentials are not known. The aim was to compare the evoked potential response to oesophageal stimulation with the cortical activity associated with anticipation of the same stimulus. In 12 healthy men (23.5 +/- 4 years), oesophageal electrical stimulation (15 mA, 0.2 Hz, 0.2 msec) was applied, and the evoked potentials recorded using scalp electrodes. A computerized model of randomly skipped stimuli (4:1 ratio) was used to separately record the evoked potentials associated with stimulation and those associated with an anticipated stimulus. The electrical stimulus represented the nontarget stimulus and the skipped impulse the target (anticipatory) stimulus. This anticipatory evoked potential was also compared to auditory P300 evoked potentials. Reproducible evoked potentials and auditory P300 responses were elicited in all subjects. Anticipatory evoked potentials (peak latency 282.1 +/- 7.9 msec, amplitude 8.2 +/- 0.7 microV, P < 0.05 vs auditory P300 evoked potential) were obtained with the skipped stimulus. This anticipatory evoked potential was located frontocentrally, while the auditory P300 potential was located in the centro-parietal cortex. The anticipatory evoked potential associated with expectation of an oesophageal stimulus, although of similar latency to that of the auditory P300 evoked response, originates from a different cortical location. The recording of cognitive evoked potentials to an expected oesophageal stimulus depends on attention to, and awareness of, the actual stimulus. Anticipatory evoked potentials to GI stimuli may provide an objective electrophysiological tool for the assessment of the cognitive factors associated with visceral perception.
Adult↗
Prevalence and impact of upper gastrointestinal symptoms in the Canadian population: findings from the DIGEST study. Domestic/International Gastroenterology Surveillance Study.
OBJECTIVE: The prevalence and impact of upper gastrointestinal (GI) symptoms in the general population are poorly defined. Most data are obtained from selected samples derived from patients presenting to health care providers. As part of a larger international effort (The DIGEST study), we examined the prevalence of upper GI symptoms among the general Canadian population, as well as their psychosocial and economic impact. METHODS: A sample of 1036 adults was studied, its demographic characteristics closely matching those of the general Canadian population. A validated detailed questionnaire measured the prevalence, severity, and frequency of 15 digestive symptoms, as well as demographic information, use of medication and medical resources, other illnesses, and dietary habits. The Psychological General Well-Being Index, a self-administered questionnaire, assessed the individual's subjective sense of well-being. RESULTS: Of the sample population, 28.6% reported substantial symptoms in the preceding 3 months, the majority (111/153 subjects) for >1 yr; 34.1% reported having never experienced significant GI symptoms. The most bothersome symptoms were primarily related to dysmotility-like symptoms in 54.9% of those with chronic symptoms, ulcer-like symptoms in 12.4%, and related to heartburn in 42.5%. Chronic upper GI symptoms were associated with a highly significant (p < 0.001) decrease in all facets of the Psychological General Well Being Index. CONCLUSIONS: Upper GI symptoms are very prevalent in the general Canadian population and substantially affect the quality-of-life and psychological well-being of those affected. Dysmotility-like symptoms, rather than heartburn, are the most common chronic upper gastrointestinal symptoms in the general population.
Adolescent↗
Long-term efficacy of Botulinum toxin in classical achalasia: a prospective study.
OBJECTIVE: We sought to examine the long-term efficacy of intrasphincteric Botulinum toxin A injection in a prospective cohort study of 30 patients with achalasia. METHODS: Thirty patients with classical achalasia were treated with intrasphincteric Botulinum toxin A injection. Follow-up consisted of clinical assessment, symptom scoring, and postinjection manometry. RESULTS: Symptomatic improvement for >3 months was seen in 23 of 30 patients (77%). Of the 23 initial responders, seven (30%) experienced a sustained symptomatic response after a single Botulinum toxin injection (mean follow-up, 21 months). The remaining 16 initial responders (70%) eventually relapsed (mean initial response, 11 months). Nine received a 2nd Botulinum toxin injection, and seven experienced an ongoing response (mean duration, 9 months); two patients eventually required a 3rd injection with good effect (mean duration, 22 months). The remaining seven patients who relapsed after Botulinum toxin opted for pneumatic dilation or surgical myotomy. Five of the seven patients who had no initial response received a 2nd injection but again did not respond. A residual lower esophageal sphincter pressure <18 mm Hg after the first Botulinum toxin injection predicted a good response to Botulinum therapy (single or multiple injections, p < 0.002, positive predictive value = 0.71, negative predictive value = 1.0). Neither initial nor sustained response to Botulinum toxin could be predicted based on gender, age, duration of illness, previous pneumatic dilation, or esophageal motility before treatment. CONCLUSIONS: We found that 77% of patients with classical achalasia experienced a good symptomatic response after Botulinum toxin and 30% of initial responders achieve sustained symptomatic relief after a single treatment with Botulinum toxin. The initial responders who relapsed did well with subsequent Botulinum toxin A. Lack of an initial symptomatic response and residual lower esophageal sphincter pressure > or =18 mm Hg after Botulinum toxin are associated with a poor response.
Adult↗
Pseudoaffective cardioautonomic responses to gastric distension in rats.
We examined the heart rate response to gastric distension, the involvement of vagal and sympathetic sensory afferents, adrenergic and cholinergic neural pathways, and the effects of capsaicin on this response in anesthetized rats. Gastric distension volume dependently decreased heart rate by 24.5% (resting rate = 219.87 +/- 14.06 beats/min, mean rate during gastric distension with 15 ml = 165.97 +/- 17.36 beats/min, P < 0.05). The bradycardic response was significantly decreased after removal of the celiac plexus (9.71 +/- 1.77 vs. 38.03 +/- 7.06% in controls, P < 0.05) or after bilateral subdiaphragmatic vagotomy (6.38 +/- 2.65%, P = 0.05). The response to gastric distension was largely prevented by systemic capsaicin (29.92 +/- 4.93% in controls, 2.58 +/- 4.19% after systemic capsaicin, P < 0.05) and decreased by perivagal capsaicin (18.72 +/- 4.75%, P < 0.05). Atropine almost completely prevented the cardiac response to distension, while propranolol and bretylium partially blocked it, implying the response is primarily mediated by cholinergic efferents but also involves adrenergic pathways. We conclude that unmyelinated, capsaicin-sensitive vagal afferents are essential to the pseudoaffective cardioautonomic response to a noxious gastric stimulus.
Animals↗
The autonomic nervous system in functional bowel disorders.
Communications along the brain-gut axis involve neural pathways as well as immune and endocrine mechanisms. The two branches of the autonomic nervous system are integrated anatomically and functionally with visceral sensory pathways, and are responsible for the homeostatic regulation of gut function. The autonomic nervous system is also a major mediator of the visceral response to central influences such as psychological stress. As defined, functional disorders comprise a constellation of symptoms, some of which suggest the presence of altered perception, while other symptoms point to disordered gastrointestinal function as the cause of the symptoms. A growing number of reports have demonstrated disordered autonomic function in subgroups of functional bowel patients. While a number of different methods were used to assess autonomic function, the reports point to a generally decreased vagal (parasympathetic) outflow or increased sympathetic activity in conditions usually associated with slow or decreased gastrointestinal motility, while other studies found either an increased cholinergic activity or a decreased sympathetic activity in patients with symptoms compatible with an increased motor activity. Under certain conditions, altered autonomic balance (including low vagal tone and increased sympathetic activity) may alter visceral perception. Autonomic dysfunction may also represent the physiological pathway accounting for many of the extraintestinal symptoms seen in irritable bowel syndrome patients and some of the frequent gastrointestinal complaints reported by patients with disorders such as chronic fatigue and fibromyalgia.
Autonomic Nervous System↗
Neurocardiac and cerebral responses evoked by esophageal vago-afferent stimulation in humans: effect of varying intensities.
OBJECTIVE: This study was designed to determine whether esophageal vago-afferent electrostimulation, over a wide range of stimulus intensities, can sustain a cardiac vago-efferent effect by way of central nervous system processing. METHODS: Studies were performed in ten healthy male subjects (23.9 +/- 6.3 years). Esophageal electrostimulation was carried out using a stimulating electrode placed in the distal esophagus. Stimulation of esophageal vago-afferent fibres was employed using electrical impulses (200 microseconds at 0.2 Hz x 128 s) varying from 2.7 to 20 mA. Respiratory frequencies, beat-to-beat heart rate autospectra and cerebral evoked potentials were recorded at baseline and at each stimulus intensity in random order. RESULTS: With esophageal electrical stimulation, we observed a small non-significant decrease in heart rate. There was a dramatic shift of the instantaneous heart rate power spectra towards enhanced cardiac vagal modulation with intensities as low as 5 mA. This effect was sustained throughout all intensities with no further change in either the low frequency or high frequency power. Conversely, there was a linear dose response relationship between cerebral evoked potential amplitude and stimulus intensity mainly occurring above perception threshold (10 mA). Esophageal stimulation had no significant effect on heart rate or respiratory frequency at any stimulus intensity. CONCLUSIONS: These results indicate that electrical stimulation of the distal esophagus across a wide range of current intensities elicits a reproducible shift in the heart rate power spectrum towards enhanced vagal modulation. The data suggest a closed loop afferent/efferent circuitry wherein tonic visceral afferent impulses appear to elicit a phasic or modulatory vago-efferent cardiac response in healthy subjects.
Adult↗
Gastric pacing as a treatment for intractable gastroparesis: shocking news?
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Electric Stimulation Therapy↗