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Lower Oesophageal Sphincter (lower + oesophageal_sphincter)
Terms modified by Lower Oesophageal Sphincter Selected AbstractsThe effect of baclofen on gastro-oesophageal reflux, lower oesophageal sphincter function and reflux symptoms in patients with reflux diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2002M. A. Van Herwaarden SUMMARY Background :,Baclofen decreases gastro-oesophageal reflux episodes in healthy subjects by reducing the incidence of transient lower oesophageal sphincter relaxations. Aim :,To investigate the effect of baclofen on reflux symptoms, oesophageal pH and lower oesophageal sphincter manometry in patients with gastro-oesophageal reflux disease. Methods :,A double-blind, placebo-controlled, two-way crossover design was used to study the effect of baclofen on heartburn and regurgitation 3 h after a provocation test meal in 37 patients with gastro-oesophageal reflux disease. Additionally, in 20 of these patients, the effect of baclofen on oesophageal pH, transient lower oesophageal sphincter relaxations and basal lower oesophageal sphincter pressure was studied. Results :,Baclofen significantly decreased the acid reflux time and the incidence of gastro-oesophageal reflux episodes (8.3 ± 8.8% vs. 12.4 ± 12.0%, P = 0.03 and 10.9 ± 7.3 per 3 h vs. 18.7 ± 12.4 per 3 h). The incidence of transient lower oesophageal sphincter relaxations was significantly lower with baclofen than with placebo (15.1 ± 6.4 per 3 h vs. 22.8 ± 5.4 per 3 h, P < 0.0001). Lower oesophageal sphincter pressure and the percentage of transient lower oesophageal sphincter relaxations associated with reflux were not affected by baclofen. No significant effect on symptom scores was observed. Conclusions :,Baclofen decreases post-prandial acid reflux in patients with gastro-oesophageal reflux disease by reducing the incidence of transient lower oesophageal sphincter relaxations. No effect of a single dose of baclofen on reflux symptoms could be demonstrated in this 3-h post-prandial study. [source] The effect of glucagon-induced gastric relaxation on TLOSR frequencyNEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2003H. Y. Chang Abstract This study aimed to determine the effect of glucagon-induced gastric relaxation on the frequency of transient lower oesophageal sphincter relaxations (TLOSRs). Eight normal subjects (four male, age 18,52 y) were studied after a 6-h fast using a combined manometric barostat assembly. The recording was divided into two 1-h sessions: (1) a baseline period with the barostat set at minimal distending pressure (MDP) + 2 mmHg and (2) a period with continuous glucagon or placebo infusion with barostat set at MDP + 2 mmHg. Patients were studied on two different days and randomly received glucagon (4.8 ,g kg,1 bolus followed by 9.6 ,g kg,1 h,1 infusion) on 1 day and placebo (saline) on another. Lower oesophageal sphincter (LOS) pressure, frequency of TLOSRs, and barostat bag volumes were determined for both placebo and glucagon infusion. Glucagon induced significant fundal relaxation compared with placebo (P < 0.05) and significantly decreased baseline LEOS pressure (P < 0.05). The frequency of TLOSRs was not altered by glucagon infusion compared with placebo. Despite causing substantial proximal stomach relaxation, glucagon did not increase TLOSR frequency. This suggests that the relevant gastric mechanoreceptors responsible for triggering TLOSRs do not respond to passive elongation. [source] Lower oesophageal sphincter dysfunction is part of the functional abnormality in epiphrenic diverticulumBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 8 2009X. B. D'Journo Background: The pathophysiology and management of epiphrenic diverticula remain controversial. This study investigated the underlying functional abnormalities and long-term results of surgical treatment. Methods: Patients with symptoms and epiphrenic diverticula who had undergone long myotomy and Belsey Mark IV fundoplication were reviewed retrospectively. They were assessed before and after surgery by radiology, functional testing and endoscopy, and compared with a group of 40 normal volunteers. Results: The study included 23 consecutive symptomatic patients who had surgery, 20 of whom had oesophageal spastic disorders. Lower oesophageal sphincter (LOS) incoordination was considered the most constant functional abnormality (P < 0·001). After operation oesophageal diameter increased, contraction pressures decreased and peristalsis was reduced. LOS resting and gradient pressures decreased (P = 0·001). Despite unchanged acid exposure values, endoscopy revealed increased mucosal damage after operation (P = 0·003). New columnar-lined metaplasia was documented in eight patients (P = 0·013). Symptoms had decreased after a median of 61 months (P = 0·001). Conclusion: Epiphrenic diverticulum was associated with spastic dysfunction and LOS abnormalities. A long myotomy including the LOS relieved functional obstruction and symptoms, but partial fundoplication did not prevent reflux damage. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Effect of paddock vs. stall housing on 24 hour gastric pH within the proximal and ventral equine stomachEQUINE VETERINARY JOURNAL, Issue 4 2008L. HUSTED Summary Reasons for performing study: Stall housing has been suggested as a risk factor for ulcer development in the equine stomach; however, the exact pathogenesis for this has not been established. Objectives: To investigate the effect of 3 environmental situations (grass paddock, stall alone or stall with adjacent companion) on pH in the proximal and the ventral stomach. Methods: Six horses with permanently implanted gastric cannulae were used in a randomised, cross-over, block design. Each horse rotated through each of three 24 h environmental situations. Horses remained on their normal diet (grass hay ad libitum and grain b.i.d.) throughout the study. Intragastric pH was measured continuously for 72 h just inside the lower oesophageal sphincter (proximal stomach) and via a pH probe in the gastric cannula (ventral stomach). Results: Neither proximal nor ventral 24 h gastric pH changed significantly between the 3 environmental situations. Mean hourly proximal gastric pH decreased significantly in the interval from 01.00,09.00 h compared to the interval from 13.00,20.00 h, regardless of environmental situation. Median hourly proximal pH only differed in the interval from 06.00,07.00 h compared to the interval 14.00,19.00 h. Neither mean nor median hourly ventral gastric pH varied significantly with the time of day. Conclusions: The change in housing status used in the current study did not affect acid exposure within either region of the equine stomach. The pH in the ventral stomach was uniformly stable throughout the study, while the proximal pH demonstrated a 24 h circadian pattern. Potential relevance: Since stall housing was not associated with prolonged acid exposure to the proximal stomach, this aspect alone does not explain the increased risk of squamous ulcer development. The circadian rhythm associated with proximal intragastric pH warrants further investigation. [source] Modulation of salivation and heartburn in response to the site of acid infusion in the human oesophagusALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010S. K. Dutta Summary Background, The pathogenesis of gastro-oesophageal reflux disease includes increased acid reflux, reduced salivation and impaired peristalsis. This may depend upon the height of acid wave and magnitude of oesophageal mucosal exposure. Interestingly, the effect of site of acid infusion upon salivary secretion and heartburn has not been examined in any detail. Aim, To examine whether acid infusion in the upper oesophagus may cause increased salivation and heartburn as compared with acid infusion in the lower oesophagus. Methods, Twelve healthy male subjects (mean age 30) received infusions of HCl, citric acid and acetic acid at 10 and 20 cm above the lower oesophageal sphincter (LES) for fixed time periods. Parotid saliva collected periodically and heartburn severity scored using standardized scale. Standard statistical methods (paired t -tests, analysis of variance) were used to determine the significance of results. Results, Acid infusion in the upper oesophagus increased parotid flow rate as compared with that in the lower oesophagus (P < 0.05). Likewise, there was a significantly increased heartburn score at 20 cm as well as 10 cm above LES (P < 0.05) as compared with that in the stomach. Conclusion, These data suggest a significant increase in salivation and heartburn in response to acid infusion in the upper vs. lower part of the oesophagus. [source] Effect of lesogaberan, a novel GABAB -receptor agonist, on transient lower oesophageal sphincter relaxations in male subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2010G. E. BOECKXSTAENS Aliment Pharmacol Ther,31, 1208,1217 Summary Background, Transient lower oesophageal sphincter relaxations (TLESRs) are a major mechanism behind gastro-oesophageal reflux disease (GERD). Aim, To assess the effect of lesogaberan (AZD3355) , a novel peripherally active GABAB receptor agonist , on TLESRs. Methods, Twenty-four healthy men were enrolled in this single-blind, placebo-controlled, randomized, single-centre, three-period crossover phase 1 study. Subjects were randomized to receive single oral doses of lesogaberan (0.8 mg/kg), baclofen (40 mg) and placebo, separated by washout periods of ,7 days. Subjects finished a meal 1 h after the dose. Oesophageal manometry and pH-metry measurements were taken during the 3 h after the meal. Results, Twenty-one subjects completed the study. Compared with placebo, lesogaberan 0.8 mg/kg significantly reduced the number of TLESRs by 36% [geometric mean ratio (GMR): 0.64; 95% confidence interval (CI): 0.51,0.82] and significantly reduced the number of acid reflux episodes (mean reduction: 1.6; 95% CI: 0.34,2.9). Lesogaberan also significantly increased lower oesophageal sphincter (LES) pressure by 39% compared with placebo (GMR: 1.39; 95% CI: 1.18,1.64). Comparable results were observed with baclofen. Similar numbers of adverse events were reported by subjects taking lesogaberan and placebo. Conclusion, Compared with placebo, lesogaberan significantly reduced TLESRs and acid reflux episodes and increased LES pressure. [source] Opiate-induced oesophageal dysmotilityALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010R. E. KRAICHELY Aliment Pharmacol Ther,31, 601,606 Summary Background, Opiates have well characterized (troublesome) untoward effects on the gastrointestinal tract. Opioid bowel dysfunction has been a subject of research and even drug design, but surprisingly little is known with regard to clinical effects of opiates on the oesophagus. Aim, To characterize opiate effects on motor function of the oesophagus in patients presenting with dysphagia. Methods, Retrospective review of 15 patients with dysphagia referred for oesophageal manometry while on chronic opiates. Manometry was completed during opiate use and in three cases, after opiates were discontinued. Results, All patients demonstrated motility abnormalities. Incomplete lower oesophageal sphincter (LOS) relaxation (11.5 ± 1.6 mmHg) was seen in most cases. Ten patients demonstrated nonperistaltic contractions in ,3 of 10 swallows. Additional abnormalities included high amplitude contractions; triple peaked contractions; and increased velocity. The average resting lower oesophageal sphincter (LOSP) met criteria for hypertensive LOS in three patients. These features were suggestive of spasm or achalasia. Repeat manometry off opiates was performed in three cases. LOS relaxation was noted to be complete upon repeat manometry in these cases. There was also improved peristalsis and normal velocity. Conclusions, A range of manometric abnormalities were seen in patients with dysphagia in the setting of opiate use: impaired LOS relaxation, high amplitude/velocity and simultaneous oesophageal waves. These data suggest that the oesophagus is susceptible to the effects of opiates and care must be taken before ascribing dysphagia to a primary oesophageal motility disorder in patients taking opiates. [source] Ethnic variation in lower oesophageal sphincter pressure and lengthALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008K. J. VEGA Summary Background, Oesophageal manometry (OM) is used to diagnose oesophageal motor disorders. Normal values of OM among United States ethnic groups are only available for Hispanic Americans (HA). Aim, To obtain normal values of OM in adult African American (AA) volunteers, compare these with those obtained in HA and non-Hispanic white (nHw) volunteers to determine if ethnic variation in normal oesophageal motor function exists. Methods, Healthy AA, HA and nHw were recruited from the Jacksonville metropolitan area. Ethnicity was self-reported. Exclusion criteria were symptoms suggestive of oesophageal disease, medication use or concurrent illness affecting OM. All underwent OM using a solid-state system with wet swallows. Resting lower oesophageal sphincter (LOS) pressure and LOS length were measured at mid-expiration, while per cent peristaltic contractions, distal oesophageal contraction velocity, amplitude and duration were measured after 5 cc water swallows. Results, Fifty-six AA, 20 HA and 48 nHw were enrolled. All completed OM. AA had significantly higher resting LOS pressure, LOS length and distal oesophageal contraction duration than nHw (P < 0.05). Conclusions, Significant ethnic exist in OM findings between AA and nHw. These underscore the need for ethnic specific reference values for OM to allow for correct diagnosis of oesophageal motor disorders in AA. [source] Review article: from 1906 to 2006 , a century of major evolution of understanding of gastro-oesophageal reflux diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2006J. DENT Summary Background Our understanding of gastro-oesophageal reflux disease has undergone significant changes over the last century. Aim To trace the rise in understanding of gastro-oesophageal reflux disease and highlight remaining areas of uncertainty. Methods Literature review. Results In 1906, Tileston published his observations on ,peptic ulcer of the oesophagus'. Winkelstein, in 1934, first correlated symptoms of heartburn with acid regurgitation and reflux oesophagitis. In 1946, Allison described hiatus hernia as a causal factor in the development of gastro-oesophageal reflux disease. In 1958, Bernstein and Baker showed a direct relationship between oesophageal acidification and heartburn in patients with gastro-oesophageal reflux disease, irrespective of endoscopic findings, leading to the recognition of non-erosive gastro-oesophageal reflux disease. In the 1980s, continuous recordings of the lower oesophageal sphincter showed that episodes of reflux were related to transient relaxations of lower oesophageal sphincter tone. There is now increasing recognition that gastro-oesophageal reflux disease arises from the interaction of several anatomical and physiological factors. A turning point in the medical treatment of gastro-oesophageal reflux disease came with the introduction of the first proton pump inhibitor, omeprazole, in 1989. Conclusions Future efforts need to identify the multifactorial interactions of gastro-oesophageal junction anatomy and physiology in patients with gastro-oesophageal reflux disease. Increased understanding of the disease will guide development of new therapies. [source] Review article: the management of heartburn in pregnancyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2005J. E. RICHTER Summary Heartburn is a normal consequence of pregnancy. The predominant aetiology is a decrease in lower oesophageal sphincter pressure caused by female sex hormones, especially progesterone. Serious reflux complications during pregnancy are rare; hence upper endoscopy and other diagnostic tests are infrequently needed. Gastro-oesophageal reflux disease during pregnancy should be managed with a step-up algorithm beginning with lifestyle modifications and dietary changes. Antacids or sucralfate are considered the first-line drug therapy. If symptoms persist, any of the histamine2 -receptor antagonists can be used. Proton pump inhibitors are reserved for women with intractable symptoms or complicated reflux disease. All but omeprazole are FDA category B drugs during pregnancy. Most drugs are excreted in breast milk. Of systemic agents, only the histamine2 -receptor antagonists, with the exception of nizatidine, are safe to use during lactation. [source] Pathophysiological characteristics of patients with non-erosive reflux disease differ from those of patients with functional heartburnALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2004M. Frazzoni Summary Background :,Patients with endoscopy-negative heartburn can be subdivided into non-erosive reflux disease and functional heartburn on the basis of abnormal and normal, respectively, oesophageal acid exposure. Different pathophysiological characteristics could explain the reportedly low efficacy of proton pump inhibitors in functional heartburn. Aim :,To assess if non-erosive reflux disease and functional heartburn are pathophysiologically distinguishable. Methods :,Oesophageal manometry and pH-monitoring were performed in 145 patients with endoscopy-negative heartburn, in 72 patients with erosive reflux disease, in 58 patients with complicated reflux disease, and in 60 controls. Results :,Patients with non-erosive reflux disease (84 cases) and functional heartburn (61 cases) differed with regard to the prevalence of hiatal hernia (49% vs. 31%, P = 0.008), the mean lower oesophageal sphincter tone (18.5 vs. 28.4 mmHg, P < 0.05), and the number of upright diurnal acid refluxes lasting more than 5 min (3.6 vs. 0.37, P < 0.05). The results were very close in thenon-erosive reflux disease, erosive reflux disease and complicated reflux disease groups, whilst patients with functional heartburn were indistinguishable from controls. Conclusions :,Pathophysiological characteristics typical of gastro-oesophageal reflux disease are found in patients with non-erosive reflux disease but not in patients with functional heartburn. This could explain the reportedly low efficacy of proton pump inhibitors in functional heartburn and suggests considering different management strategies. [source] The effect of baclofen on gastro-oesophageal reflux, lower oesophageal sphincter function and reflux symptoms in patients with reflux diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2002M. A. Van Herwaarden SUMMARY Background :,Baclofen decreases gastro-oesophageal reflux episodes in healthy subjects by reducing the incidence of transient lower oesophageal sphincter relaxations. Aim :,To investigate the effect of baclofen on reflux symptoms, oesophageal pH and lower oesophageal sphincter manometry in patients with gastro-oesophageal reflux disease. Methods :,A double-blind, placebo-controlled, two-way crossover design was used to study the effect of baclofen on heartburn and regurgitation 3 h after a provocation test meal in 37 patients with gastro-oesophageal reflux disease. Additionally, in 20 of these patients, the effect of baclofen on oesophageal pH, transient lower oesophageal sphincter relaxations and basal lower oesophageal sphincter pressure was studied. Results :,Baclofen significantly decreased the acid reflux time and the incidence of gastro-oesophageal reflux episodes (8.3 ± 8.8% vs. 12.4 ± 12.0%, P = 0.03 and 10.9 ± 7.3 per 3 h vs. 18.7 ± 12.4 per 3 h). The incidence of transient lower oesophageal sphincter relaxations was significantly lower with baclofen than with placebo (15.1 ± 6.4 per 3 h vs. 22.8 ± 5.4 per 3 h, P < 0.0001). Lower oesophageal sphincter pressure and the percentage of transient lower oesophageal sphincter relaxations associated with reflux were not affected by baclofen. No significant effect on symptom scores was observed. Conclusions :,Baclofen decreases post-prandial acid reflux in patients with gastro-oesophageal reflux disease by reducing the incidence of transient lower oesophageal sphincter relaxations. No effect of a single dose of baclofen on reflux symptoms could be demonstrated in this 3-h post-prandial study. [source] Dysfunction of oesophageal motility in Helicobacter pylori -infected patients with reflux oesophagitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2001J. C. Y. Wu Background: Helicobacter pylori infection has been suggested to be protective against gastro-oesophageal reflux disease. However, a significant proportion of patients with gastro-oesophageal reflux disease are infected by H. pylori. Aim: To study oesophageal motor function in H. pylori -infected patients with reflux oesophagitis. Methods: Patients with erosive reflux oesophagitis were recruited prospectively for stationary oesophageal manometry and 24-h ambulatory oesophageal pH monitoring. H. pylori status was determined by biopsy urease test. Non-reflux volunteers were recruited as controls. Results: Seventy-four patients with erosive oesophagitis (34 H. pylori -positive, 40 H. pylori -negative) and 48 non-reflux patient controls (22 H. pylori -positive, 26 H. pylori -negative) were recruited. There was no difference in severity of oesophagitis (median grade, 1; P=0.53) or oesophageal acid exposure (total percentage time oesophageal pH < 4, 7.6% vs. 6.8%; P=0.57) between H. pylori -positive and H. pylori -negative groups. Compared to H. pylori -negative patients, H. pylori -positive patients had significantly lower basal lower oesophageal sphincter pressure (12.2 mmHg vs. 15.3 mmHg; P=0.03) and amplitude of distal peristalsis (56.9 mmHg vs. 68.4 mmHg; P=0.03). Ineffective oesophageal motility (14% vs. 7%; P=0.02) and failed oesophageal peristalsis were also significantly more prevalent in H. pylori -positive patients. Conclusions: Among patients with a similar degree of reflux oesophagitis, H. pylori -infected patients have more severe oesophageal dysmotility and lower oesophageal sphincter dysfunction. Oesophageal motor dysfunction probably plays a dominant role in the development of gastro-oesophageal reflux disease in patients with H. pylori infection. [source] Lower oesophageal sphincter relaxation evoked by stimulation of the dorsal motor nucleus of the vagus in ferretsNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2002T. P. Abrahams Abstract, An understanding of the neural control of lower oesophageal sphincter (LOS) relaxation is clinically relevant because transient LOS relaxations (TLOSRs) are a mechanism of acid reflux into the oesophagus. Preganglionic motor neurones innervating the LOS are localized in the dorsal motor nucleus of the vagus (DMV). Based on a single study in cats, it is now widely accepted that these neurones are functionally organized into two separate populations, such that stimulation of the caudal and rostral DMV evokes LOS relaxation and contraction, respectively. Our goal was to map the functional LOS responses to chemical stimulation in the DMV and nucleus tractus solitarius (NTS) of ferrets, an animal model commonly used for conscious studies on TLOSRs, and to test whether DMV-evoked LOS relaxation is mediated through hexamethonium-sensitive vagal-inhibitory pathways to the LOS. We used miniaturized manometry with Dentsleeve to monitor LOS and oesophageal pressures in decerebrate unanaesthetized ferrets. LOS relaxation was evoked readily in response to gastric insufflation, which shows that the vago,vagal reflex was intact in this preparation. Microinjections of l -glutamate (12.5 nmol L,1in 25 nL) were made into the DMV from approximately ,,1.5 to +,2.0 mm relative to the obex. Microinjections into the caudal (, 1.5 to +,0.0 mm behind obex) and intermediate (+ 0.1 to +,1.0 mm rostral to obex) DMV both significantly decreased LOS pressure, and complete LOS relaxation was noted in 28/32 and 11/18 cases, respectively. LOS relaxation responses to DMV microinjection were highly reproducible and abolished by bilateral vagotomy or hexamethonium (15 mg kg,1intravenously). A nitric oxide synthase inhibitor (l -NAME 100 mg kg,1intramuscularly) significantly increased the time taken to reach the maximal response. Increases in LOS pressure (24 ± 4 mmHg; n = 3) were obtained only when stimulation sites were located equal to greater than 1.5 mm rostral to the obex. LOS relaxation (, 78 ± 10%; n = 6) was evoked by stimulation of the NTS but not immediately outside of the NTS (11 ± 27%; n = 5). We conclude that there is a very extensive population of ,inhibitory' motor neurones in the DMV that may account for the predominant vagal-inhibitory tone in ferrets. As NTS stimulation evokes LOS relaxation and the predominant response to DMV stimulation is also LOS relaxation, this vago,vagal reflex may involve an excitatory interneurone between the NTS and DMV vagal inhibitory output. [source] Prolonged recording of oesophageal and lower oesophageal sphincter pressure using a portable water-perfused manometric systemNEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2001M. A. Van Herwaarden The aim of our study was to investigate the recording fidelity of a water-perfused micromanometric catheter with incorporated sleeve combined with a newly developed portable water-perfused manometric system for pharyngeal, oesophageal and lower oesophageal sphincter (LOS) pressure recording. The system's performance was assessed in prolonged recordings in ambulant gastro-oesophageal reflux disease (GORD) patients. Eighty 24-h studies in GORD patients, carried out with the perfused portable manometric system, were evaluated. Twelve of these recordings were analysed in detail in order to compare oesophageal and LOS motor patterns with those described previously. Paired 2-h manometric recordings of the pharynx, oesophagus, LOS and stomach, using the new system and a conventional perfused stationary manometric system, were performed in eight healthy subjects. With the portable manometric system oesophageal contractions, transient LOS relaxations, swallow-associated prolonged LOS relaxations and LOS pressures were recorded with equal fidelity to the conventional manometric system. Recordings obtained with the portable system showed meal-related and diurnal variations in oesophageal and LOS variables that were similar to these found in studies using conventional equipment. The new manometric system, consisting of a perfused micromanometric catheter with incorporated sleeve and a portable perfusion system, enables prolonged studies on oesophageal and LOS motor patterns in ambulant subjects. [source] Effect of endotoxin on opossum oesophageal motor functionNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2000H. Park Endotoxin induces nitric oxide (NO,) synthase and alters gastrointestinal functions. We explored the effect of lipopolysaccharide (LPS) on oesophageal motor function at 6, 12, 24, and 48 h. The effects of inhibiting inducible NO, synthase (iNOS) were studied 12 h after administration of LPS with/without aminoguanidine (AG). Oesophageal manometry was performed and tissue bath studies were performed with muscle strips from the oesophagus and lower oesophageal sphincter (LOS). Plasma nitrite/nitrate concentrations were determined. The amplitudes of peristaltic pressure waves, resting LOS pressure and the percentage LOS relaxations were diminished by LPS. AG attenuated the decrease in amplitude of oesophageal pressure waves, LOS pressure, and percentage relaxation of LOS brought about by LPS. LPS decreased electrical field stimulation (EFS)-induced relaxation of LOS muscle. AG attenuated this decrease in LOS relaxation. The off-response of transverse oesophageal muscle strips was decreased, and AG antagonized this effect. Plasma concentrations of nitrite/nitrate were increased. The increase in plasma nitrite/nitrate was attenuated by AG. These studies support the hypothesis that endotoxin modulates oesophageal motor function by increasing NO production and suggest that this results from the induction of iNOS. [source] Preoperative prediction of long-term outcome following laparoscopic fundoplicationANZ JOURNAL OF SURGERY, Issue 7 2002Colm J. O'Boyle Background: Although long-term outcomes following laparoscopic fundoplication for gastro-oesophageal disease have now been reported as very satisfactory, a small, but important, minority of patients are unhappy with the outcome, often due to recurrent reflux symptoms or new-onset dysphagia. In this study, we sought to establish whether various parameters that can be determined before surgery, can predict the long-term outcome of surgery. Methods: Data collected prospectively were evaluated to determine factors that were associated with outcome at 5 years following laparoscopic fundoplication. Inclusion criteria were complete preoperative assessment data and 5-year follow-up data. Data examined included information on preoperative age, sex, weight, home address, health insurance status, duration of reflux symptoms, previous surgery, operating surgeon, endoscopy and 24-h pH monitoring. In addition, lower oesophageal sphincter resting and residual relaxation pressures were evaluated before and after surgery. The postoperative symptoms of heartburn and dysphagia, as well as overall satisfaction 5 years following surgery was determined using a 0,10 visual analogue scale. The association of the pre- and perioperative factors and outcome at 5 years was determined by univariate and linear regression analysis. Results: Two hundred and sixty-two patients from an overall experience of over 1000 laparoscopic anti-reflux procedures met the entry criteria. There was no association between patient address, age, weight, duration of symptoms, the presence of endoscopically proven oesophagitis, operating surgeon, the necessity for conversion to an open procedure, change in lower oesophageal sphincter residual relaxation pressure and the outcome parameters. Using univariate analysis, a higher heartburn score was associated with previous abdominal surgery, female sex, no private health insurance, and a normal preoperative 24-h pH study. A higher dysphagia score was associated with a normal preoperative pH study, a postoperative increase in lower oesophageal sphincter resting pressure of more than 6 mmHg, and previous abdominal surgery. Overall satisfaction with the outcome at 5 years was higher among male patients, private patients, patients who had a hiatus hernia, and patients who had an abnormal preoperative pH study. Linear regression analysis confirmed that private insurance, male sex, and the absence of previous abdominal surgery, were the strongest predictors of an improved heartburn score, whereas male sex and private health insurance were the strongest predictors of greater satisfaction with the overall outcome. Conclusions: There are parameters that can be assessed before or during laparoscopic Nissen fundoplication that correlate with late outcome parameters. In particular, male patients and those from higher socioeconomic groups appear to have a better long-term outcome. [source] NO/cyclic GMP pathway mediates the relaxation of feline lower oesophageal sphincterAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2003C. H. Jun Summary 1 We examined the role of the NO/cyclic GMP (cyclic GMP) pathway in nitric oxide (NO)- and vasoactive intestinal peptide (VIP)-induced relaxation of feline lower oesophageal sphincter (LES). Furthermore, it was studied whether methylene blue, LY83583 and ODQ, which are soluble guanylate cyclase (sGC) inhibitors, could inhibit NO-induced relaxation. 2 The nitric oxide synthase (NOS) inhibitor, N -nitro- l -arginine (l -NNA) had no effect in sodium nitropruside (SNP)-induced relaxation, but 3-morpholinosydnonimine- N -ethylcarbamide (SIN-1)-induced relaxation was decreased by the pretreatment of l -NNA, which showed that SIN-1, not SNP, could activate NOS to cause relaxation. Methylene blue and LY83583 did not inhibit the relaxation by SNP and SIN-1. However, the more specific sGC inhibitor ODQ blocked the relaxation induced by NO donors. 3 To identify the relationship of NOS, sGC and adenylate cyclase in VIP-induced relaxation, tissue were pretreated with l -NNA and ODQ and SQ22536. These inhibitors produced significant inhibition of this response to VIP. The adenylyl cyclase inhibitor SQ 22536 also inhibited relaxation by VIP. 4 In conclusion, our data showed that SNP- and SIN-1-induced relaxation was mediated by sGC. Of sGC inhibitors, methylene blue and LY83583 were not adequate for the examination of NO donor-induced feline LES smooth muscle relaxation. VIP also caused relaxation by the pathway involving NO and cGMP and cAMP. [source] |