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Biomedical subjects

J Dent

Publications and source records attributed to J Dent.

At least 55 records · Page 3Linked to original sources

Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease.

OBJECTIVES: Brief, reliable, and valid self-administered questionnaires could facilitate the diagnosis of gastroesophageal reflux disease in primary care. We report the development and validation of such an instrument. METHODS: Content validity was informed by literature review, expert opinion, and cognitive interviewing of 50 patients resulting in a 22-item survey. For psychometric analyses, primary care patients completed the new questionnaire at enrollment and at intervals ranging from 3 days to 3 wk. Multitrait scaling, test-retest reliability, and responsiveness were assessed. Predictive validity analyses of all scales and items used specialty physician diagnosis as the "gold standard." RESULTS: Iterative factor analyses yielded three scales of four items each including heartburn, acid regurgitation, and dyspepsia. Multitrait scaling criteria including internal consistency, item interval consistency, and item discrimination were 100% satisfied. Test-retest reliability was high in those reporting stable symptoms. Scale scores significantly changed in those reporting a global change. Regressing specialty physician diagnosis on the three scales revealed significant effects for two scales (heartburn and regurgitation). Combining the two significant scales enhanced the strength of the model. Symptom response to self-directed treatment with nonprescription antisecretory medications was highly predictive of the diagnosis also, although the item demonstrated poor validity and reliability. CONCLUSIONS: A brief, simple 12-item questionnaire demonstrated validity and reliability and seemed to be responsive to change for reflux and dyspeptic symptoms.

Adult↗

Relationship between straining, transient lower esophageal sphincter relaxation, and gastroesophageal reflux in children.

OBJECTIVE: Physical straining such as deep inspiration or coughing may induce gastroesophageal reflux (GER) by overcoming feeble lower esophageal sphincter (LES) pressure. The role of straining as a provocant of GER has not been analyzed systematically in children. It was our aim to examine the contribution of straining to the occurrence of GER with particular attention to its relationship to transient LES relaxations, which are a major mechanism of the occurrence of GER in pediatric patients. METHODS: Concurrent esophageal manometry and pH monitoring was performed for 4 h postprandially in six children with esophagitis (age 9 months to 12 yr). Analysis was performed on isolated single strain episodes, defined as an increased intragastric pressure > 10 mm Hg. When a drop of esophageal pH < 4.0 was noted within 15 sec after any part of a strain, this strain was defined as related to the reflux episode. RESULTS: The median value of basal LES pressure was 10 mm Hg (range 1-18). In all, 134 analyzable strains and 87 analyzable reflux episodes were recorded. Isolated strains were associated with 20 reflux episodes (23%). Reflux was observed more frequently with strains that occurred during transient LES relaxations (12/40) than straining when the LES was contracted (8/94) (p < 0.01). Sustained strain (35%) and inspiratory strain (25%) were the major patterns of straining related to reflux. CONCLUSION: Straining provoked reflux infrequently and simultaneous occurrence of straining and transient LES relaxation was important in determining the occurrence of strain-related reflux in pediatric patients with reflux esophagitis.

Child↗

Small intestinal motor patterns in critically ill patients after major abdominal surgery.

OBJECTIVES: In patients who have had major surgery or trauma, early enteral feeding is safer and more effective than parenteral or nasogastric feeding but is frequently associated with diarrhea. Limited recordings have shown that the patterning of duodenal interdigestive motor activity is frequently abnormal after surgery or in patients who are critically ill. The aims of this study were to evaluate the effects of major abdominal surgery on small intestinal motility, and to elucidate the motor patterns that occur postoperatively in critically ill patients in response to enteral feeding. METHODS: The effects of elective aortic aneurysm repair on small intestinal motility were studied in 11 patients aged 63-77 yr. A 3.5-mm diameter multilumen extrusion was used to monitor pressures at 12 points, distributed between the antrum and 100 cm distal to the pylorus. An additional lumen allowed enteral feeding into the duodenum. Recordings commenced immediately postoperatively and continued for up to 4 days. Data are given as means and SEMs. RESULTS: Bursts (frequency > 10/min) of small intestinal pressure waves that resembled phase III interdigestive motor activity occurred in all patients immediately after surgery. During mechanical ventilation, the timing of bursts along the segment evaluated was frequently abnormal for true interdigestive phase III activity, with simultaneous onset in multiple channels (46%), multiple or distal origins (8%), or retrograde migration (20%). When patients were not being ventilated, the migration pattern of the bursts was more typical of interdigestive phase III activity. The interval between bursts was unusually short for interdigestive motor activity, although it increased from 30+/-12 min on day 1 to 41+/-18 min on day 3 (p < 0.05). A phase II pattern of pressure waves was virtually absent in all patients on all study days. In six patients who received postoperative enteral nutrition, the bursts of pressure waves were not abolished by feeding, contrary to normal phase III activity. CONCLUSIONS: Small intestinal pressure wave bursts are seen immediately after elective aortic aneurysm repair, but the migration of these bursts is frequently abnormal for phase III interdigestive activity. Duodenal nutrient delivery did not interrupt the occurrence of these bursts. Persistence of pressure wave bursts in this setting may be important in the delivery of enteral nutrition.

Aged↗

Nutrient-induced spatial patterning of human duodenal motor function.

The spatiotemporal patterning of duodenal motor function has been evaluated comprehensively for the first time in humans, with a novel 21-lumen manometric assembly. In nine young, healthy volunteers (6 male, 3 female), duodenal motility was recorded during fasting and three 45-min intraduodenal (ID) nutrient infusion periods (Intralipid at 0.25, 0.5, and 1.5 kcal/min). Pressures were recorded along the length of the duodenum with an array of 18 sideholes at 1.5-cm intervals. Pressure patterns were compared for the final 20 min of each of the four periods. Compared with fasting, ID lipid was associated with regional variation in pressure wave (PW) sequences, with fewer proximally and more distally; this was not observed during fasting (P < 0.001). During fasting and all rates of lipid infusion, most (87-90%) PW sequences were short (1.5-4.5 cm), with a small number (2-4%) of 10.5 cm or longer. At all times, antegrade PW sequences occurred more frequently than retrograde sequences over all distances examined (3, 4.5, and >6 cm), and the proportion of antegrade sequences increased with greater PW sequence length (P = 0.0001). Increasing ID lipid rates appeared to produce dose-related suppression of PW sequences (P < 0.001). The frequency and spatial patterning of human duodenal motor function show substantial variability in response to different nutrient delivery rates. These complex patterns are likely to be involved in duodenal modulation of flow and gastric emptying rate.

Adult↗

Relationship between ultrasonically detected phasic antral contractions and antral pressure.

The relationships between gastric wall motion and intraluminal pressure are believed to be major determinants of flows within and from the stomach. Gastric antral wall motion and intraluminal pressures were monitored in five healthy subjects by concurrent antropyloroduodenal manometry and transabdominal ultrasound for 60 min after subjects drank 500 ml of clear soup. We found that 99% of antral contractions detected by ultrasound were propagated aborally, and 68% of contractions became lumen occlusive at the site of the ultrasound marker. Of the 203 contractions detected by ultrasound, 53% were associated with pressure events in the manometric reference channel; 86% of contractions had corresponding pressure events detectable somewhere in the antrum. Contractions that occluded the lumen were more likely to be associated with a pressure event in the manometric reference channel (P < 0.01) and to be of greater amplitude (P < 0.01) than non-lumen-occlusive contractions. We conclude that heterogeneous pressure event patterns in the antrum occur despite a stereotyped pattern of contraction propagation seen on ultrasound. Lumen occlusion is more likely to be associated with higher peak antral pressure events.

Adolescent↗

Pressure-geometry relationship in the antroduodenal region in humans.

Understanding of the control mechanisms underlying gastric motor function is still limited. The aim of the present study was to evaluate antral pressure-geometry relationships during gastric emptying slowed by intraduodenal nutrient infusion and enhanced by erythromycin. In seven healthy subjects, antral contractile activity was assessed by combined dynamic magnetic resonance imaging and antroduodenal high-resolution manometry. After intragastric administration of a 20% glucose solution (750 ml), gastric motility and emptying were recorded during intraduodenal nutrient infusion alone and, subsequently, combined with intravenous erythromycin. Before erythromycin, contraction waves were antegrade (propagation speed: 2.7 +/- 1.7 mm/s; lumen occlusion: 47 +/- 14%). Eighty-two percent (51/62) of contraction waves were detected manometrically. Fifty-four percent of contractile events (254/473) were associated with a detectable pressure event. Pressure and the degree of lumen occlusion were only weakly correlated (r(2) = 0.02; P = 0.026). After erythromycin, episodes of strong antroduodenal contractions were observed. In conclusion, antral contractions alone do not reliably predict gastric emptying. Erythromycin induces strong antroduodenal contractions not necessarily associated with fast emptying. Finally, manometry reliably detects ~80% of contraction waves, but conclusions from manometry regarding actual contractile activity must be made with care.

Duodenum↗

Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa.

BACKGROUND & AIMS: The efficacy and safety of long-term acid suppression remains a subject for debate. We report data from patients with refractory reflux esophagitis who were undergoing maintenance therapy with >/=20 mg omeprazole daily for a mean period of 6.5 years (range, 1.4-11.2 years). METHODS: Patients with severe reflux esophagitis resistant to long-term therapy with H(2)-receptor antagonists and who were not eligible for surgery were evaluated at least annually for endoscopic relapse and histological changes in the gastric corpus. RESULTS: In 230 patients (mean age, 63 years at entry; 36% were >/=70 years), there were 158 relapses of esophagitis during 1490 treatment years (1 per 9.4 years), with no significant difference in relapse rates between Helicobacter pylori-positive and -negative patients. All patients rehealed during continued therapy with omeprazole at the same or higher dose. The annual incidence of gastric corpus mucosal atrophy was 4.7% and 0.7% in H. pylori-positive and -negative patients, respectively, which was mainly observed in elderly patients who had moderate/severe gastritis at entry. In patients with baseline moderate/severe gastritis, the incidences were similar: 7.9% and 8.4%, respectively. Corpus intestinal metaplasia was rare, and no dysplasia or neoplasms were observed. The adverse event profile was as might be expected from this elderly group of patients. CONCLUSIONS: Long-term omeprazole therapy (up to 11 years) is highly effective and safe for control of reflux esophagitis.

Adolescent↗

Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects.

BACKGROUND & AIMS: Transient lower esophageal sphincter (LES) relaxations are the major mechanism of gastroesophageal reflux in normal subjects and in most patients with reflux disease. gamma-Aminobutyric acid (GABA) is an important inhibitory neurotransmitter within the central nervous system which is present in regions of the brainstem that are believed to mediate transient LES relaxations. The aim of this study was to investigate the effect of a GABA(B) agonist baclofen on postprandial gastroesophageal reflux and transient LES relaxations. METHODS: In 20 healthy volunteers, esophageal motility and pH were measured, with the subjects in the sitting position, for 3 hours after a 3000-kJ mixed nutrient meal. On separate days at least 1 week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal. RESULTS: Baclofen significantly reduced the rate of reflux episodes by more than 60% from 1.0 (0.3-2.7) to 0.3 (0-1.0) per hour (median [interquartile range]). Baclofen also reduced the rate of transient LES relaxations from 5.7 (4.9-7.8) to 2.2 (1.3-3.8) per hour and increased basal LES pressure from 8.7 +/- 1.4 to 10.8 +/- 0.8 mm Hg. CONCLUSIONS: In normal human subjects, the GABA(B) agonist baclofen significantly inhibits gastroesophageal reflux by inhibition of transient LES relaxations. These findings suggest that GABA(B) agonists may be useful as therapeutic agents for the management of reflux in patients with gastroesophageal reflux disease.

Adolescent↗

GABA(B) receptor-mediated effects on vagal pathways to the lower oesophageal sphincter and heart.

GABA(B) receptors influencing vagal pathways to the lower oesophageal sphincter and heart were investigated. In urethane-anaesthetized ferrets, the GABA(B) agonist baclofen (7 micromol kg(-1) i.v.) increased basal lower oesophageal sphincter (LOS) pressure. This was reversed by antagonism with CGP35348 (100 micromol kg(-1) i.v.). Baclofen's effect was abolished by vagotomy, suggesting a central action, yet it was ineffective when given centrally (3 - 6 nmol i.c.v.). Peripheral vagal stimulation (10 Hz, 5 s duration) caused LOS inhibition, followed by excitation, then prolonged inhibition. Bradycardia was also evoked during stimulation. Bradycardia and LOS responses were abolished after chronic supranodose vagotomy, indicating that they were due to stimulation of vagal pre-ganglionic neurones, not antidromic stimulation of afferents. Baclofen (1 - 10 micromol kg(-1)) reduced bradycardia and enhanced LOS excitation, which was also seen in animals pretreated with atropine (400 microgram kg(-1) i.v.) and guanethidine (5 mg kg(-1) i.v.), but not in those pretreated with L-NAME (100 mg kg(-1) i.v.). Effects of baclofen (7 micromol kg(-1) i.v.) on vagal stimulation-induced LOS and cardiac responses were unchanged by the GABA(B) antagonists CGP35348 or CGP36742 (up to 112 micromol kg(-1) i.v.), but were reversed by CGP62349 (ED(50) 37 nmol kg(-1) i.v.) or CGP54626 (ED(50) 100 nmol kg(-1) i.v.). Responses of isolated LOS strips to electrical stimulation, capsaicin, NK-1, NK-2 and nicotinic receptor agonists were all unaffected by baclofen (</=200 microM). We conclude that baclofen reduces vagal output at two peripheral sites: one presynaptically on pre-ganglionic neurones (CGP35348-insensitive), and another (CGP35348-sensitive) that could not be identified. This demonstrates heterogeneity of GABA(B) receptors through differential sensitivity to antagonists.

Animals↗

Personal review: alarmism or legitimate concerns about long-term suppression of gastric acid secretion?

This article responds to controversial issues about the long-term use of acid suppression raised in a recent article in this journal by Waldum & Brenna. Although rebound acid secretion occurs following proton pump inhibitor therapy, the clinical significance of this is unclear, but the proposal that this is a major driver of acid-related diseases is considered implausible. The polypoid deformity of the gastric corpus that can occur with long-term proton pump inhibitor therapy is not neoplastic, and therefore has no bearing on other issues raised about proton pump inhibitor therapy and gastric malignancy. Current data in humans suggest that the magnitude of serum gastrin elevation from proton pump inhibitor treatment of up to 10 years, and any theoretical risks from this, have been overstated by Waldum & Brenna. Pernicious anaemia is a model of very doubtful validity for the risks of proton pump inhibitor therapy on several grounds. The proposal that diffuse gastric carcinoma arises from acid suppression-induced stimulation of enterochromaffin-like cells is challenged vigorously, because this is based on an implausible and substantially criticized interpretation of histopathology. It is agreed that it is appropriate to be cautious about the safety of long-term acid suppression, because no data are available for lifelong treatment in humans. Such caution should be tempered by a critical assessment of the benefits of this treatment in relation to any possible risks. The substantial data that now exist from long-term treatment of humans with proton pump inhibitors has not thus far revealed any definite risks. The risk of death from anti-reflux surgery, although small, would seem to far exceed any possible risks associated with long-term proton pump inhibitor use. Available data suggest that denial of the benefits of effective acid suppressant therapy to patients with clear-cut troublesome acid related disorders is an overreaction to concerns about the biological effects of inhibiting acid secretion with proton pump inhibitors.

Animals↗

Controversies in long-term management of reflux disease.

There are significant controversies about the long-term therapy of reflux disease that arise primarily from a lack of data on the risks of the disease and its therapies over the relevant time scale of several decades. Currently, there are no appropriately structured direct comparisons between the two current major treatment options of tailored long-term acid suppression and laparoscopic anti-reflux surgery. Critical review of the available literature does not support the assertion that anti-reflux surgery has a superior risk/benefit profile when compared to long-term proton pump inhibitor (PPI) therapy, since non-controlled data indicate that although both therapies are relatively safe, morbidity and mortality rates are lowest with PPI therapy, whilst efficacy is comparable. The clinical significance of the reflux that continues to occur after both anti-reflux surgery and during PPI therapy is uncertain, but probably over-estimated. As pathological duodenogastro-oesophageal reflux affects only a small minority of reflux disease patients, issues arising from it should not be regarded as mainstream influences on the choice of long-term therapy. Notwithstanding, this type of reflux is substantially reduced by both PPI therapy and anti-reflux surgery. The choice between laparoscopic surgery and long-term tailored acid suppression should be determined primarily by assessment of operative risk, the quality of surgery available to the patient and by patient preference, after balanced explanation of the risks and benefits of each option. Given that the cost of PPI therapy is likely to drop substantially in the next few years, drug cost should not be a major pressure for the choice of anti-reflux surgery.

Anti-Ulcer Agents↗

Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.

BACKGROUND & AIMS: One-year lamivudine therapy significantly suppressed hepatitis B virus (HBV) replication, improved hepatic necroinflammatory activity, and prevented progression of fibrosis. However, the effects of prolonged therapy are unknown. METHODS: A total of 334 Asian patients with chronic hepatitis B from a previously reported 1-year study were randomized to receive either lamivudine (100 or 25 mg) or placebo for another year. The effects of treatment on serum HBV-DNA suppression, alanine transaminase (ALT) normalization, and hepatitis B e antigen (HBeAg) seroconversion were measured. The presence of YMDD variant HBV and its effect were also determined. RESULTS: A significantly greater proportion of patients achieved sustained HBV-DNA suppression and ALT normalization with 100 mg lamivudine daily for 2 years compared with lamivudine for 1 year followed by placebo for the second year (P<0.001). Daily lamivudine therapy for 2 years was safe and resulted in incremental HBeAg seroconversion from 17% at week 52 to 27% at week 104. HBeAg seroconversion during continued lamivudine therapy increased linearly with increasing pretherapy ALT levels (P< 0.001). Despite the emergence of YMDD mutant in 38% of the patients, they continued to clear serum HBeAg and maintain lower median serum HBV-DNA and ALT levels than baseline values. In contrast, ALT levels increased 8-12 weeks after switching from lamivudine to placebo, but returned to normal once lamivudine treatment was resumed. CONCLUSIONS: Treatment with lamivudine for 2 years is both well tolerated and efficacious in patients with chronic hepatitis B.

Adult↗

Behavior and gastroesophageal reflux in the premature neonate.

BACKGROUND: The belief that behavioral observations assist in the clinical diagnosis of gastroesophageal reflux (GER) disease in premature neonates has not been formally tested. The purpose of this study was to determine whether esophageal acidification was associated with a recognizable pattern of behavioral changes in these infants. METHODS: The behavior of 14 healthy premature infants was recorded by a video camera while esophageal pH was simultaneously monitored. For each of 20 acid GER episodes recorded, a 10-minute video epoch, encompassing the onset of acid GER and lasting at least 4 minutes after the onset of GER, was examined. Two independent observers each scored reflux-associated epochs of "general" infant behavior and behavior previously shown to be indicative of reflux in normal term infants. RESULTS: The occurrence of esophageal acidification due to reflux did not significantly alter scores for general behavior. Infants frequently demonstrated reflux-specific behavior, including discomfort, head retraction, and mouthing; however, none of these behavioral patterns was temporally associated with the occurrence of acid GER. CONCLUSIONS: These data indicate that reflux-specific behavioral criteria, established in older term infants, may be inappropriate as diagnostic criteria for GER in premature neonates and may lead to the unnecessary use of antireflux therapy.

Behavior↗

Long-term effects of pyloromyotomy on pyloric motility and gastric emptying in humans.

OBJECTIVE: The aim of this study was to determine the long term effects of pyloromyotomy for infantile hypertrophic pyloric stenosis (IHPS) on gastric emptying and pyloric motility. METHODS: Concurrent measurements of gastric emptying and antropyloroduodenal pressures were performed in six volunteers (aged 24-26 yr) who had had pyloromyotomy performed in infancy because of IHPS, and in six normal subjects. Subjects were studied on 2 days, once sitting and once in the left lateral position. Gastric emptying of 300 ml 25% dextrose labeled with 20 MBq 99mTc sulfur colloid was measured. Antropyloroduodenal motility was evaluated with a sleeve/multiple sidehole manometric assembly, which was also used to deliver an intraduodenal triglyceride infusion at 1.1 kcal/min for 60 min, starting 30 min after ingestion of the dextrose. RESULTS: In both body positions, gastric emptying and intragastric distribution of the drink did not differ between the two groups. In both groups and postures, the amount emptied was less during intraduodenal lipid infusion. The number (p<0.01) and amplitude (p<0.02) of isolated pyloric pressure waves (IPPWs) was greater in the control subjects, whereas basal pyloric pressure was greater in the pyloromyotomy subjects (p<0.02). In both groups, the rate of gastric emptying in the sitting position was related to the number of IPPWs (r> or =0.40, p<0.05), but not to basal pyloric pressure. CONCLUSIONS: These results indicate that, in adults who have had pyloromyotomy for IHPS in infancy, patterns of pyloric motility are abnormal; pyloric tone is higher, whereas the number and amplitude of phasic pyloric pressure waves are less. In contrast, the overall rate of gastric emptying of a nutrient liquid meal is normal. These observations are consistent with the concept that the stomach has the capacity to compensate for changes in pyloric motility to minimize effects on gastric emptying.

Adult↗

Impacts and patterns of disturbed gastrointestinal function in critically ill patients.

Disordered upper gastrointestinal tract motility occurs frequently in intensive care unit patients and often represents a substantial treatment challenge. In addition to specific complications such as pulmonary aspiration and diarrhea, abnormal gastrointestinal motility is a limiting factor for delivery and success of enteral nutrition. The pathophysiologies involved are incompletely understood because of the difficulties of making measurements of gastrointestinal function in critically ill patients. With the recent development of techniques that overcome some of these difficulties, the prospects are brighter for significant advances in this field.

Critical Illness↗

Relationships between spatial patterns of colonic pressure and individual movements of content.

The aim of this study was to examine the relationship between colonic pressure waves and movement of content. In 11 healthy subjects, pressures were recorded at 10-cm intervals from cecum to rectum for 32 h. In six subjects, transit was simultaneously measured for 8 h after direct cecal instillation of 1.5 mCi of (99m)Tc sulfur colloid. Thirty-two percent of isotope movements were related to nonpropagating activity and twenty-eight percent to propagating sequences. The extent of isotope movement related to propagating sequences (25.1 +/- 2.1 cm) was greater than that due to nonpropagating activity (12.8 +/- 0.7 cm; P = 0.0001). Propagating sequences originated significantly more frequently (P = 0.004) and propagated further (P = 0.0006) in the proximal compared with the distal colon. Only 36% of propagating sequences were propulsive of content, and compared with nonpropulsive sequences, these propagated further (41 +/- 6 vs. 27 +/- 2 cm; P < 0.05) and had a higher probability of originating proximally (P = 0.0003), a higher pressure wave amplitude (50 +/- 5 vs. 34 +/- 4 mmHg; P = 0.0001), and slower velocity (2.2 +/- 0.3 vs. 3.6 +/- 0.47 cm/s; P = 0.02). We conclude that most movements of colonic content are related to pressure waves. There is marked regional variation in the prevalence, velocity, and extent of propagation of propagating pressure wave sequences, which are an important mechanism for transporting content over long distances. The effectiveness of transport by a propagating sequence is influenced by its site of origin, amplitude, and velocity.

Adolescent↗

Relative contributions of "pressure pump" and "peristaltic pump" to gastric emptying.

The relative contributions to gastric emptying from common cavity antroduodenal pressure difference ("pressure pump") vs. propagating high-pressure waves in the distal antrum ("peristaltic pump") were analyzed in humans by high-resolution manometry concurrently with time-resolved three-dimensional magnetic resonance imaging during intraduodenal nutrient infusion at 2 kcal/min. Gastric volume, space-time pressure, and contraction wave histories in the antropyloroduodenal region were measured in seven healthy subjects. The subjects fell into two distinct groups with an order of magnitude difference in levels of antral pressure activity. However, there was no significant difference in average rate of gastric emptying between the two groups. Antral pressure history was separated into "propagating high-pressure events" (HPE), "nonpropagating HPEs," and "quiescent periods." Quiescent periods dominated, and average pressure during quiescent periods remained unchanged with decreasing gastric volume, suggesting that common cavity pressure levels were maintained by increasing wall muscle tone with decreasing volume. When propagating HPEs moved to within 2-3 cm of the pylorus, pyloric resistance was found statistically to increase with decreasing distance between peristaltic waves and the pylorus. We conclude that transpyloric flow tends to be blocked when antral contraction waves are within a "zone of influence" proximal to the pylorus, suggesting physiological coordination between pyloric and antral contractile activity. We further conclude that gastric emptying of nutrient liquids is primarily through the "pressure pump" mechanism controlled by pyloric opening during periods of relative quiescence in antral contractile wave activity.

Adult↗

Triggering of transient LES relaxations in ferrets: role of sympathetic pathways and effects of baclofen.

Activation of gastric vagal mechanoreceptors by distention is thought to be the trigger for transient lower esophageal sphincter relaxations (TLESR), which lead to gastroesophageal reflux. The contribution of higher-threshold gastric splanchnic mechanoreceptors is uninvestigated. GABA(B) receptor agonists, including baclofen, potently reduce triggering of TLESR by low-level gastric distention. We aimed to determine first whether this effect of baclofen is maintained at high-level distention and second the role of splanchnic pathways in triggering TLESR. Micromanometric/pH studies in conscious ferrets showed that intragastric glucose infusion (25 ml) increased triggering of TLESR and reflux. Both were significantly reduced by baclofen (7 micromol/kg ip) (P < 0.05). When 40 ml of air was added to the glucose infusion, more TLESR occurred than with glucose alone (P < 0.01). These were also reduced by baclofen (P < 0.001). TLESR after glucose/air infusion were assessed before and after splanchnectomy (2-4, 9-11, and 23-25 days), which revealed no change. Baclofen inhibits TLESR after both low- and high-level gastric distention. Splanchnic pathways do not contribute to increased triggering of TLESR by high-level gastric distention.

Animals↗