Transient Lower Esophageal Sphincter Relaxations Research Articles

T1687 The Effect of Salivary Nitrite on Gastro-Esophageal Reflux

Introduction Human saliva has a high nitrite concentration from the entero-salivary recirculation of dietary nitrate. Swallowed nitrite reacts with gastric acid to form nitric oxide (NO) at the gastro-oesophageal junction. This may contribute to the pathogenesis of reflux disease. NO has been shown to reduce lower oesophageal sphincter (LOS) pressure, impair oesophageal clearance and may be the final mediator in the production of transient lower oesophageal sphincter relaxations (TLOSRs). Aims To determine (1) whether nitrite in saliva increases oesophageal acid exposure and (2) whether nitrite in swallowed saliva modifies the manometric characteristics of the LOS and distal oesophagus. Methods 20 asymptomatic subjects (11 males) were studied. Each underwent endoscopy to document normal anatomy. On four separate days, high-resolution manometry and pH were performed during 15 min fasting and for 90 min following a standardised meal. Postprandially, solutions containing 0, 0.286, 2 and 14 mmol/l potassium nitrite were infused into the oral cavity. Solutions were randomised and double-blinded. Saliva was collected at baseline, 30, 60 and 90 min following the meal. Nitrite concentrations were quantified by Griess reaction. Acid exposure was calculated as per cent time pH Results Salivary nitrite concentrations at 60 min were 24.35 μmol/l (3.86–65.46), 80.42 μmol/l (20.88–158.79), 358.4 μmol/l (118.2–726.6) and 2694 μmol/l (600–8087) for the solutions containing 0, 0.286, 2 and 14 mmol/l nitrite, respectively. There was no difference in acid exposure between the control and the nitrite-containing solutions (p>0.04). There was no difference in the number (p>0.05), duration (p>0.4) or nadir pH (p>0.2) of reflux events. The mean number of TLOSRs and the reduction in postprandial LOS pressure were similar (p>0.04 and p>0.07). There was no difference in peristaltic wave velocity or amplitude (p>0.1 and p>0.6). Conclusion Despite an excellent range of salivary nitrite concentrations, over and beyond the normal physiological range, no difference in oesophageal acid exposure or oesophageal motility was seen between the control solution and those containing nitrite. These findings suggest that salivary nitrite does not potentiate oesophageal reflux.

T1883 Upper Esophageal Sphincter Relaxation as a Determinant of Reflux and Symptoms During Transient Lower Esophageal Sphincter Relaxation (TLESR)?

T1883 Upper Esophageal Sphincter Relaxation as a Determinant of Reflux and Symptoms During Transient Lower Esophageal Sphincter Relaxation (TLESR)?

T1911 Ingestion of Carbonated Drinks Decreases Lower Esophageal Sphincter (LES) Pressure and Increases Transient LES Relaxations

T1911 Ingestion of Carbonated Drinks Decreases Lower Esophageal Sphincter (LES) Pressure and Increases Transient LES Relaxations

Beyond Acid Suppression: New Pharmacologic Approaches for Treatment of GERD

Proton pump inhibitors are highly successful in treating gastroesophageal reflux disease, but a significant proportion of patients have persistent symptoms from weakly or nonacidic reflux. Transient lower esophageal sphincter relaxation (TLESR) represents the dominant mechanism of gastroesophageal reflux and has therefore become the most intensely investigated therapeutic target. The triggering of TLESR involve the vagal pathways and the gamma-aminobutyric type B (GABA(B)) and metabotropic glutamate type 5 (mGluR5) receptors. Baclofen is a GABA(B) receptor agonist that is effective in inhibiting TLESR and reducing the number of reflux episodes, but is associated with significant central nervous system (CNS) side effects. The newer GABA(B) agonists, such as AZD9343 and AZD3355, and mGluR5 antagonists, such as 2-methyl-6-(phenylethynyl)-pyridine (MPEP), have been shown in small, randomized, controlled trials to have comparable efficacy to baclofen, but possibly a more favorable CNS side effect profile. Cannibinoid agonists, such as Delta(9)-THC, have also been demonstrated to reduce TLESRs and reflux events respectively. Macrolide antibiotics (eg, erythromycin) show early promise in a select group of patients with possible reflux associated post-lung transplant problems.

PWE-080 Effect of gastric emptying on pressure-flow dynamics of oesophago-gastric junction

<h3>Introduction</h3> Oesophago-gastric junction (OGJ) incompetence is a primary determinant of gastrooesophageal reflux disease (GORD) severity. Especially, the pressure-flow gradients across the OGJ during lower oesophageal sphincter (LOS) relaxation have important implications in GORD pathogenesis and subsequent planning of its treatment. Our aim was to evaluate the pressure-flow dynamic changes occurring at GOJ barrier during transient lower oesophageal sphincter relaxation (TLOSRs) and study the impact of gastric emptying after a meal on those events using combined high-resolution manometery and high-resolution impedance monitoring (HRMZ, ManoScan Z™). <h3>Methods</h3> HRMZ was performed in eight healthy subjects (6M and 2F, 27±7 years) for 4 h after a refluxogenic meal (1000 kcal). Pressure–flow dynamics of OGJ during TLOSR events including their frequency, duration, gastro-oesophageal pressure gradient (GO pressure gradient) and proximal extent of migration of the reflux episodes were computed. Gastric emptying of the meal was assessed by 13C-labelled octanoic acid breath test and gastric emptying lag time, half emptying time and gastric retention time were calculated. <h3>Results</h3> All subjects completed the study. During TLOSR events there was reciprocal relationship between GE pressure grad. and retrograde flow of gastric contents, the gradient was greatest at the onset of retrograde flow, decreasing progressively as the flow continued and became lowest by the end of flow across the OGJ (GO pressure gradient start of flow=9.5±2.6, peak flow=6.05±2.5 (p=&lt;0.05), end of flow=2.3±2.5 (p=&lt;0.001). GE pressure gradient was significantly higher for TLOSRs accompanied by significant retrograde flow (obvious flow on HRMZ display) compared with episodes with limited flow (&lt;3 impedance channels) (12.90±1.101 vs 6.858±1.388, p=0.01). TLOSR episodes accompanied by significant flow reached the upper oesophagus much more frequently than those episodes with limited flow (mean height of reflux episodes=13.46±3.4 vs 5.16±1.3, p=0.001). Significant correlation between height of reflux episodes and gastric retention time (r=0.7, p=0.04) week correlation trends were observed with gastric emptying lag time (r=0.4) and half emptying times (r=0.3). <h3>Conclusion</h3> Our results suggest HRMZ is effective in elucidating the pressure-flow dynamics of OGJ. The proximal extent of the reflux episode correlates with gastric retention time of the meal; however other gastric emptying parameters did not show significant correlation despite promising trends. Further studies involving GORD patients might give us important insights into the role of OGJ pressure flow dynamics in the pathophysiology of GORD.

PP-017 The effect of salivary nitrite on gastro-oesophageal reflux

<h3>Introduction</h3> Human saliva has a high nitrite concentration from the entero-salivary recirculation of dietary nitrate. Swallowed nitrite reacts with gastric acid to form nitric oxide (NO) at the gastro-oesophageal junction. This may contribute to the pathogenesis of reflux disease. NO has been shown to reduce lower oesophageal sphincter (LOS) pressure, impair oesophageal clearance and may be the final mediator in the production of transient lower oesophageal sphincter relaxations (TLOSRs). <h3>Aims</h3> To determine (1) whether nitrite in saliva increases oesophageal acid exposure and (2) whether nitrite in swallowed saliva modifies the manometric characteristics of the LOS and distal oesophagus. <h3>Methods</h3> 20 asymptomatic subjects (11 males) were studied. Each underwent endoscopy to document normal anatomy. On four separate days, high-resolution manometry and pH were performed during 15 min fasting and for 90 min following a standardised meal. Postprandially, solutions containing 0, 0.286, 2 and 14 mmol/l potassium nitrite were infused into the oral cavity. Solutions were randomised and double-blinded. Saliva was collected at baseline, 30, 60 and 90 min following the meal. Nitrite concentrations were quantified by Griess reaction. Acid exposure was calculated as per cent time pH&lt;4. The number of reflux events was calculated and reflux event characteristics (duration and nadir pH) recorded. TLOSRs were determined using established criteria. Mean LOS pressure, peristaltic wave velocity and peristaltic amplitude were also calculated. To adjust for multiple comparisons the Bonferroni method was used with p&lt;0.017 considered significant. Results are medians and ranges unless stated. <h3>Results</h3> Salivary nitrite concentrations at 60 min were 24.35 μmol/l (3.86–65.46), 80.42 μmol/l (20.88–158.79), 358.4 μmol/l (118.2–726.6) and 2694 μmol/l (600–8087) for the solutions containing 0, 0.286, 2 and 14 mmol/l nitrite, respectively. There was no difference in acid exposure between the control and the nitrite-containing solutions (p&gt;0.04). There was no difference in the number (p&gt;0.05), duration (p&gt;0.4) or nadir pH (p&gt;0.2) of reflux events. The mean number of TLOSRs and the reduction in postprandial LOS pressure were similar (p&gt;0.04 and p&gt;0.07). There was no difference in peristaltic wave velocity or amplitude (p&gt;0.1 and p&gt;0.6). <h3>Conclusion</h3> Despite an excellent range of salivary nitrite concentrations, over and beyond the normal physiological range, no difference in oesophageal acid exposure or oesophageal motility was seen between the control solution and those containing nitrite. These findings suggest that salivary nitrite does not potentiate oesophageal reflux.

T1580: Induced Transient Lower Esophageal Sphincter Relaxation Demonstrate Differential Relaxation of the Components of the Gastroesophageal Junction

Transient lower esophageal sphincter relaxations (TLESRs) are difficult to study because they are infrequent isolated events.

Mechanism of gastroesophageal reflux in patients with obstructive sleep apnea syndrome

It has been reported that the prevalence of gastroesophageal reflux (GER) disease is high in patients with obstructive sleep apnea (OSA). End-inspiratory intra-esophageal pressure decreases progressively during OSA, which has been thought to facilitate GER in OSA patients. The aim of our study was to clarify the mechanisms of GER during sleep (sleep-GER) in OSA patients. Eight OSA patients with reflux esophagitis (RE), nine OSA patients without RE, and eight healthy controls were studied. Polysomnography with concurrent esophageal manometry and pH recording were performed. Significantly more sleep-GER occurred in OSA patients with RE than without RE or in controls (P < 0.05). The severity of OSA did not differ between OSA patients with RE and without RE. Sleep-GER was mainly caused by transient lower esophageal sphincter relaxation (TLESR), but not by negative intra-esophageal pressure during OSA. During OSA gastroesophageal junction pressure progressively increased synchronous to intra-esophageal pressure decrease. OSA patients had significantly more TLESR events during sleep related to preceding arousals and shallow sleep, but the number of TLESR events was not related to RE. In OSA patients, sleep-GER was mainly caused by TLESR, but not by negative intra-esophageal pressure due to OSA.

The novel, peripherally restricted GABA B receptor agonist lesogaberan (AZD3355) inhibits acid reflux and reduces esophageal acid exposure as measured with 24-h pHmetry in dogs

While patients with symptoms of gastroesophageal reflux disease generally respond well to proton pump inhibitors, 20–30% continue to experience troublesome symptoms. In such cases, agents that target transient lower esophageal sphincter (LES) relaxation may be useful as add-on therapy to proton pump inhibitors. The GABA B receptor agonist baclofen inhibits transient LES relaxation but it is not an ideal agent due to central nervous system activity. Lesogaberan (AZD3355) is a peripherally restricted GABA B receptor agonist with limited central nervous system activity that inhibits transient LES relaxation in dogs. In the present study, the comparative effects of lesogaberan (7 µmol/kg) and baclofen (2.8 μmol/kg) on reflux were studied in dogs using 24-h pHmetry. Drugs (or vehicle control) were administered orally prior to the first meal of the day, and the number of reflux episodes (pH < 4 for ≥ 5 s) and acid exposure time were computed for the 24-h monitoring period. The mean (S.E.M.) number of reflux episodes/24 h was 4.6 (0.4) and 6.4 (0.6) for lesogaberan and baclofen, respectively, versus 10.7 (0.5) for control ( P < 0.0001 for both). Acid exposure time was 51.2 (4.5) min for control versus 23.6 (3.8) min for lesogaberan ( P < 0.0001) and 35.4 (6.5) min with baclofen ( P = 0.05). It is concluded that lesogaberan significantly reduces acid reflux in dogs, with comparable efficacy to baclofen.

Upper esophageal sphincter during transient lower esophageal sphincter relaxation: effects of reflux content and posture.

Although some studies show that the upper esophageal sphincter (UES) contracts during transient lower esophageal sphincter relaxation (TLESR), others show that it relaxes. We hypothesized that the posture of the subject and constituents of gastroesophageal reflux (GER) may determine the type of UES response during the TLESR. High-resolution manometry and esophageal pH/impedance recording were performed in 10 healthy volunteers in the right recumbent (1 h) and upright (1 h) positions following the ingestion of a 1,000-Kcal meal. The UES pressure response during TLESR and constituents of GER (liquid, air, and pH) were determined. 109 TLESRs (58 upright and 51 recumbent) were analyzed. The majority of TLESRs were associated with GER (91% upright and 88% recumbent) events. UES relaxation was the predominant response during upright position (81% of TLESRs), and it was characteristically associated with presence of air in the reflux (92%). On the other hand, UES contraction was the predominant response during recumbent position (82% of TLESRs), and it was mainly associated with liquid reflux (71%). The rate of esophageal pressure increase (dP/dt) during the GER, but not the pH, had major influence on the type of UES response during TLESR. The dP/dt during air reflux (127 +/- 39 mmHg/s) was significantly higher than liquid reflux (31 +/- 6 mmHg/s, P < 0.0001). We concluded that the nature of UES response during TLESR, relaxation or contraction, is related to the posture and the constituents of GER. We propose that the rapid rate of esophageal pressure increase associated with air reflux determines the UES relaxation response to GER.

Small Volumes of Feed Can Trigger Transient Lower Esophageal Sphincter Relaxation and Gastroesophageal Reflux in the Right Lateral Position in Infants

To investigate the threshold amount of constantly infused feed needed to trigger lower esophageal sphincter relaxation (TLESR) in the right lateral position (RLP) and left lateral position (LLP). Eight healthy infants (3 male; gestational age: 32.9 +/- 2.4 weeks; corrected age: 36.1 +/- 1.3 weeks) were studied using an esophageal impedance-manometry catheter incorporating an intragastric infusion port. After tube placement, infants were randomly positioned in RLP or LLP. They were then tube-fed their normal feed (62.5 [40 to 75] mL) at an infusion rate of 160 mL/h. Recordings were made during the feed and 15 minutes thereafter. The study was repeated with the infant in the opposite position. More TLESRs were triggered in the RLP compared with LLP (4.0 [3.0 to 6.0] vs 2.5 [1.0 to 3.0], P = .027). First TLESR occurred at a significantly lower infused volume in RLP compared with LLP (10.6 +/- 9.4 vs 21.0 +/- 4.9 mL, P = .006). The percentage of feed infused at time of first TLESR was significantly lower in RLP compared with LLP (17.6% +/- 15.5% vs 35.4% +/- 8.02%, P = .005). In the RLP, TLESRs and gastroesophageal reflux are triggered at volumes unlikely to induce gastric distension.

Gastroesophageal Reflux Disease in Indonesia

Gastroesophageal reflux disease (GERD) is one of the problems in gastroenterology which causes major disturbance in the quality of life and daily activity. GERD can be divided into erosive and non-erosive type. GERD develops by many factors i.e. anatomical and physiological disorder, hereditary or acquired factors, genetic, diet, certain drugs, and obesity. The principle pathophysiology of GERD is an imbalance between aggressive factors and defensive factors. The aggressive factors include gastric acid, pepsin, bile acid reflux, and trypsin. The defensive factors include hypotensive lower esophageal sphincter (LES), transient lower esophageal sphincter relaxations (TLESR), hiatal hernia, disrupted saliva production, esophageal peristaltic disorder. The complications of GERD divided into esophageal and extra esophageal complications. The complications in the esophagus which can be found are bleeding, stricture, perforation, Barret’s esophagus and esophageal cancer. The complications in the extra esophagus are sore throat, tonsillo-pharyngitis, sinusitis, laryngitis, dental caries, pneumonia, asthma bronchiale, etc. Studies in Indonesia reveal that GERD is increasing recently. Syam et al. reported that the prevalence of GERD in Cipto Mangunkusumo hospital was increasing from 5.7% in 1997 to 25.18% in 2002. From the extrapolated statistic, the prevalence of GERD in Indonesia can be predicted as 7,153,588 patients from 238,452,952 populations. In this edition we have two studies on GERD. The first study studied the frequency scale for the symptoms of GERD score for GERD in Koja hospital Jakarta. Ndraha found that the most frequent characteristic of GERD was female patient, age less than 40 years old, normal body mass index (BMI). The frequency scale for the symptoms of GERD (FSSG) revealed the mean of total score was 17.6 ± 6.9. GERD patients have a high mean FSSG score, whereas dysmotility was more dominant than acid reflux. The second study studied obesity as a risk factor of erosive GERD in Cipto Mangunkusumo hospital Jakarta. Sijabat et al. found from their study that the most frequent characteristic of GERD was grade A esophagitis, female patients and mean age 48.61 ± 8.64 years old. There was a correlation between obesity or abdominal obesity and erosive GERD. The prevalence of GERD in Indonesia is increasing and this data is inline with the reports from other countries in ASIA and USA. The management of GERD is performed in keeping with Indonesian and Asia Pacific consensus, life-style modification and administering the acid suppression agents (proton pump inhibitor, H2-receptor antagonist, etc), prokinetic agents.

A Gut Feeling about GABA: Focus on GABAB Receptors

γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the body and hence GABA-mediated neurotransmission regulates many physiological functions, including those in the gastrointestinal (GI) tract. GABA is located throughout the GI tract and is found in enteric nerves as well as in endocrine-like cells, implicating GABA as both a neurotransmitter and an endocrine mediator influencing GI function. GABA mediates its effects via GABA receptors which are either ionotropic GABAA or metabotropic GABAB. The latter which respond to the agonist baclofen have been least characterized, however accumulating data suggest that they play a key role in GI function in health and disease. Like GABA, GABAB receptors have been detected throughout the gut of several species in the enteric nervous system, muscle, epithelial layers as well as on endocrine-like cells. Such widespread distribution of this metabotropic GABA receptor is consistent with its significant modulatory role over intestinal motility, gastric emptying, gastric acid secretion, transient lower esophageal sphincter relaxation and visceral sensation of painful colonic stimuli. More intriguing findings, the mechanisms underlying which have yet to be determined, suggest GABAB receptors inhibit GI carcinogenesis and tumor growth. Therefore, the diversity of GI functions regulated by GABAB receptors makes it a potentially useful target in the treatment of several GI disorders. In light of the development of novel compounds such as peripherally acting GABAB receptor agonists, positive allosteric modulators of the GABAB receptor and GABA producing enteric bacteria, we review and summarize current knowledge on the function of GABAB receptors within the GI tract.

The role of excessive esophageal acid exposure in patients with gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD), especially reflux esophagitis (RE), is characterized by excessive esophageal acid exposure. Transient lower esophageal sphincter (LES) relaxation is the major mechanism of acid reflux episodes in both healthy subjects (HS) and patients with GERD. In the sitting position, where acid reflux episodes often occur, there is no difference in the frequency of transient LES relaxations between these two groups; however, in patients with GERD, at 5cm above the LES, the proportion of acid reflux episodes during transient LES relaxations is significantly greater than in the HS group. This difference is considered to be one of the causes of excessive esophageal acid exposure in patients with GERD, but its cause is still unclear. A recent study, which investigated the proportion of acid reflux episodes during transient LES relaxations at 2 and 7cm above the LES, showed that there was no difference at 2cm above the LES between HS and patients with RE, but at 7cm they were significantly greater in patients with RE than in HS. Evaluation of acid reflux at 2cm above the LES is difficult to measure, but the proximal extent of refluxate could be one of the important factors of excessive acid esophageal exposure in patients with RE. Ineffective esophageal motility, found in patients with moderate to severe RE, impairs esophageal bolus clearance of acid, therefore both the proximal extent of refluxate and the delay of esophageal bolus clearance of acid could be major causes of excessive esophageal acid exposure. Hiatus hernia also causes acid reflux, due to its association with hypotensive LES, and also impairs esophageal bolus clearance of acid.

Transient lower oesophageal sphincter relaxation in achalasia: everything but LOS relaxation

In conducting clinical high-resolution oesophageal pressure topography (HROPT) studies we observed that after subjects sat upright between series of supine and upright test swallows, they frequently had a transient lower oesophageal sphincter relaxation (TLOSR). When achalasia patients were studied in the same protocol, they exhibited a similar HROPT event leading to the hypothesis that achalasics had incomplete TLOSRs. We reviewed clinical HROPT studies of 94 consecutive non-achalasics and 25 achalasics. Studies were analyzed for a TLOSR-like event during the study and, when observed, that TLOSR-like event was characterized for the degree and duration of distal oesophageal shortening, the degree of LOS relaxation, associated crural diaphragm (CD) inhibition, oesophageal pressurization and upper oesophageal sphincter (UOS) relaxation. About 64/94 (68%) non-achalasics and 15/24 (63%) of achalasics had a pressure topography event after the posture change characterized by a prolonged period of distal oesophageal shortening and/or LOS relaxation. Events among the non-achalasics and achalasics were similar in terms of magnitude and duration of shortening and all were associated with CD inhibition. Similar proportions had associated non-deglutitive UOS relaxations. The only consistent differences were the absence of associated LOS relaxation and the absence of HROPT evidence of reflux among the achalasics leading us to conclude that their events were incomplete TLOSRs. Achalasic patients exhibit a selective defect in the TLOSR response suggesting preservation of all sensory, central and efferent aspects of the requisite neural substrate with the notable exception of LOS relaxation, a function of inhibitory (nitrergic) myenteric plexus neurons.

The GABAB receptor agonist AZD9343 inhibits transient lower oesophageal sphincter relaxations and acid reflux in healthy volunteers: a phase I study

Transient lower oesophageal sphincter relaxations (TLESRs) represent an interesting target for the treatment of gastro-oesophageal reflux. Baclofen reduces TLESRs and reflux episodes, but is not optimal for clinical application because of its central side effects. Therefore, new agents are required. To study the effect of AZD9343, a new selective GABA(B) receptor agonist, in healthy volunteers. A total of 27 subjects participated in a placebo-controlled, randomized, two-centre phase I study. Subjects underwent oesophageal manometry and pH-metry for 3 h postprandially. Before meal ingestion, a single oral dose of placebo, 60 and 320 mg AZD9343 or 40 mg baclofen was given on four separate days. Somnolence was reported after 320 mg AZD9343 and baclofen. Reversible short-lasting paraesthesia was reported after AZD9343. AZD9343 320 mg and baclofen significantly reduced the number of TLESRs with 32% and 40% respectively. Acid reflux was significantly decreased by AZD9343 and baclofen. Like baclofen, AZD9343 increased LES pressure before meal intake. AZD9343 320 mg and baclofen significantly reduced the swallowing rate. Like baclofen, AZD9343 dose-dependently decreases the number of TLESRs and acid reflux episodes, increases LES pressure and reduces swallowing, extending the concept that GABA(B) agonists are potent reflux inhibitors. However, discovery of analogues with an improved side effect profile is warranted.

Landmarks in the understanding and treatment of reflux disease

The last 50 years have seen a transformation in the understanding and treatment of reflux disease. The development and wide use of flexible endoscopy and progressively more sophisticated approaches to measurement of pathophysiological factors have been major drivers of advances. The recognition and progressive elucidation of the mechanical events that comprise the transient lower esophageal sphincter relaxation and how they lead to reflux provide a novel and firm foundation for tailoring therapies that act directly to reduce occurrence of reflux episodes, either surgically or pharmacologically. Novel GABA(B) agonist drugs have been shown to inhibit transient relaxations and are currently being evaluated in clinical trials on patients with reflux disease. Better understanding has extended to recognition of the extraordinarily high prevalence of reflux disease and of the ability of proton pump inhibitor drugs to deliver major benefits to a high proportion of patients with reflux disease. The life of the Gastroenterological Society of Australia has spanned the period of these major advances. A large number of the members of the Society and their associates have contributed substantially to these advances.

A Case of Successful Treatment of Rumination Syndrome with Baclofen

Purpose: 24 year old female referred to Gastroenterology clinic for a second opinion about her 2 year history of “postprandial emesis”. For two years, patient was labelled with GERD and post-prandial emesis. The referring physician initiated a proton pump inhibitor with partial relief of substernal burning, but no change in the symptom of post-prandial emesis. In fact, the patient was actually describing an effortless intra-prandial, and immediately post-prandial volume reflux and regurgitation, without any nausea, abdominal cramping, or involuntary tightening of the abdominal muscles. This typically occured while sitting at the lunch table. Spicy foods and chocolate seemed to exacerbate her symptoms. She stopped eating lunch at work secondary to feelings of embarrassment in front of her coworkers, and subsequently lost 20 pounds. Symptoms spontaneously resolved for several months and then returned. Prior testing included a normal abdominal ultrasound, an esophagram revealing prominent reflux and hypomotility, a normal upper endoscopy, normal esophageal manometry, and a gastric emptying study revealing borderline slow emptying (55 percent retention at two hours). She tried taking metoclopramide for two weeks but this provided no symptomatic relief and she discontinued its use. In our opinion, her clinical symptoms were felt to be most consistent with rumination syndrome, and she was started on baclofen 10 mg tid. Discussion: Although rumination syndrome has previously been described among the institutionalized and mentally challenged, it has been increasingly recognized among individuals with normal neurological function and mental capacity. It has been attributed to be a subconscious but learned reflex of transient, voluntary relaxation of the lower esophageal sphincter. It is often accompanied by weight loss and mild, non-specific abnormalities on motility testing. Anti-reflux medications and measures are not typically helpful. Although baclofen use has not previously been reported for this syndrome, it has been shown to reduce the number of transient lower esophageal sphincter relaxation events. The patient was started on baclofen 10 mg po tid with prompt and complete relief of her symptoms.

Fifty years of Australian gastroenterology and hepatology: A golden era of contributions to the region

Fifty years of Australian gastroenterology and hepatology: A golden era of contributions to the region

Sensory and Motor Innervation of the Crural Diaphragm by the Vagus Nerves

During gastroesophageal reflux, transient lower esophageal sphincter relaxation and crural diaphragm (CD) inhibition occur concomitantly. Modifying vagus nerve control of transient lower esophageal sphincter relaxation is a major focus of development of therapeutics for gastroesophageal reflux disease, but neural mechanisms that coordinate the CD are poorly understood. Nerve tracing and immunolabeling were used to assess innervation of the diaphragm and lower esophageal sphincter in ferrets. Mechanosensory responses of vagal afferents in the CD and electromyography responses of the CD were recorded in novel in vitro preparations and in vivo. Retrograde tracing revealed a unique population of vagal CD sensory neurons in nodose ganglia and CD motor neurons in brainstem vagal nuclei. Anterograde tracing revealed specialized vagal endings in the CD and phrenoesophageal ligament-sites of vagal afferent mechanosensitivity recorded in vitro. Spontaneous electromyography activity persisted in the CD following bilateral phrenicotomy in vivo, while vagus nerve stimulation evoked electromyography responses in the CD in vitro and in vivo. We conclude that vagal sensory and motor neurons functionally innervate the CD and phrenoesophageal ligament. CD vagal afferents show mechanosensitivity to distortion of the gastroesophageal junction, while vagal motor neurons innervate both CD and distal esophagus and may represent a common substrate for motor control of the reflux barrier.