Proximal colonic propagating pressure waves sequences and their relationship with movements of content in the proximal human colon

Abstract  Abnormal colonic motor patterns have been implicated in the pathogenesis of severe constipation. Yet in health, the mechanical link between movement of colonic content and regional pressures have only been partially defined. This is largely due to current methodological limitations. Utilizing a combination of simultaneous colonic manometry, high-resolution scintigraphy and a quantitative technique for detecting discrete episodic flow, our aim was to examine the propulsive properties of colonic propagating sequences (PS) in the healthy colon. In six healthy volunteers a nasocolonic manometry catheter was positioned to record colonic pressures at 7.5 cm intervals from terminal ileum to the splenic flexure. With subjects positioned under a gamma camera, 30 MBq of ^99mTc sulfur colloid was instilled into the terminal ileum, 22.5 cm proximal to the ileocolonic junction. Isotopic images were recorded (10 s/frame) and synchronized with the manometric trace. In the proximal colon we identified 137 antegrade PSs, of which 93% were deemed to be associated temporally with movements of luminal content. Low amplitude PSs, with component pressure waves between 2 mmHg and 5 mmHg, were as likely to be associated with colonic movements as higher amplitude PSs. As such there was no correlation between the amplitude of the PS and the temporal relationship with colonic movements. Within the proximal colon, 24 retrograde PSs were identified, 23 of which were associated with retrograde movements of colonic content. We conclude that proximal colonic PSs are highly propulsive and are a major determinant of proximal colonic flow.     

Ileal manometry in children following ileostomies and pull-through operations

Our aim was to analyse the patterns of ileal contractions in children. We reviewed the charts of 23 children who had ileal manometry studies (16 males), mean age 7 years (range 2 months to 17 years). We positioned the manometry catheters with 4-8 recording sites, 5 or 15 cm apart, through ileostomies fashioned for clinically indicated reasons. We studied six additional children with persistent faecal soiling following endorectal pull through for Hirschsprung's disease; the catheters were positioned through the anus and colon into the ileum. We recorded phasic and tonic intermittent contractions in all the subjects, clustered contractions (rate 5-9 min-1, duration 20-120 s) in 19 subjects with ileostomies and four with endorectal pull throughs. In 13 children there were prolonged propagated contractions, > 60 mmHg in amplitude, > 15 s in duration, propagating at rates of 2-6 cm s-1 over at least 20 cm. The migrating motor complex was rare; in 55 h of fasting recording there were two phase III sequences. There are four distinctive features of ileal manometry recordings in children: random intermittent contractions, clustered contractions, prolonged propagated contractions and tonic contractions. The features of ileal motility differ from motility in the proximal small bowel.     

Bowel preparation affects the amplitude and spatiotemporal organization of colonic propagating sequences

Background Colonic manometry is performed using either colonoscopically assisted catheter placement, after bowel preparation, or nasocolonic intubation of the unprepared bowel. There has been little systematic evaluation of the effects of bowel cleansing upon colonic propagating pressure wave sequences. Methods Eight healthy volunteers underwent nasocolonic placement of a water‐perfused silicone catheter which recorded pressures at 16 recording sites each spaced 7.5 cm apart in the unprepared colon for 24 h. These measures were compared with those obtained in another eight healthy volunteers in whom the catheter was placed to the caecum at colonoscopy in the prepared colon. Key Results The colonic motor responses to meals and morning waking, and the normal nocturnal suppression did not differ between the two groups, nor were the overall frequency, regional dependence nor extent of propagating sequences (PS) influenced by bowel preparation. Bowel preparation did result in a significant increase in the frequency of high amplitude PS (22 ± 7 vs 8 ± 4 HAPS/24 h; P = 0.003). Additionally, a number of the measures of spatiotemporal organization among consecutive PS (linkage among sequences and predefecatory stereotypical patterning) were significantly altered by bowel preparation. Conclusions & Inferences The overall frequency of PSs, the colonic responses to physiological stimuli such a meal and morning waking and nocturnal suppression, are not influenced by prior bowel preparation. However, investigators wishing to study HAPS frequency, or the more complex spatiotemporal relationships among consecutive PSs, should control for bowel preparation when making comparisons among study groups.     

Effect of extrinsic denervation on muscarinic neurotransmission in the canine ileocolonic region

To explore the hypothesis that denervation hypersensitivity increases ileocolonic motor activity after extrinsic denervation, we compared muscarinic neurotransmission in canine ileocolonic loops that were isolated and either extrinsically innervated or extrinsically denervated. We recorded ileal, ileocolonic sphincter (ICS) and colonic pressures, and colonic tone, compliance and relaxation during ileal distention. Muscarinic effects were probed by neostigmine, and minimally effective doses of muscarinic receptor antagonists. Denervation augmented ileal, ICS and colonic contractile activity; colonic high-amplitude propagating contractions (HAPCs) were also augmented; colonic relaxation during ileal distention was abolished. Neostigmine induced HAPCs in both loop preparations. Pirenzipine (M1 antagonist) reduced ileal contractile activity in all loops and reduced colonic relaxation during ileal distention in innervated loops. Pirenzipine also reduced colonic tone and colonic HAPCs, more in denervated loops. Darifenacin (M3 antagonist) reduced ileocolonic contractile activity and tone more than did AF-DX 116 (M2 antagonist) in all loops. Cholinergic receptor subtypes modulate different facets of ileocolonic motor activity in the canine ileocolonic region. Increased sensitivity at M1 muscarinic receptors may partly account for the effects of extrinsic denervation.     

Removal of tonic nitrergic inhibition is a potent stimulus for human proximal colonic propagating sequences

Propagating sequences (PS) are important in colonic propulsion and defecation, yet the triggers of these motor patterns are not understood. Nonadrenergic noncholinergic neurones are believed to modulate smooth muscle in the gastrointestinal tract via the ubiquitous inhibitory neurotransmitter nitric oxide (NO). In the mouse colon periods of quiescence correlate with an increase in the release of NO. We investigated the colonic response to NO synthase inhibition in the conscious human subject. Intravenous infusion of saline or N(G)-monomethyl-L-arginine (L-NMMA; 3 or 6 mg kg(-1) h(-1)) occurred in random order in six healthy volunteers in whom a 5 m long nasocolonic manometry catheter was positioned such that 16 recording sites, at 7.5-cm intervals, spanned the terminal ileum and colon. L-NMMA infusion at 3 mg kg(-1) h(-1), but not 6 mg kg(-1) h(-1) significantly (P = 0.02) increased proximal colonic PS frequency (2.0 +/- 1.9 vs 11.7 +/- 7.0 PS h(-1)) and non-propagating motor activity (5,296 +/- 2,750 vs 6,362 +/- 1,275 mmHg s). We conclude that blockade of NO synthesis has a stimulatory effect on the frequency of proximal colonic PS. This suggests removal of tonic nitrergic inhibition of the colon might be a physiological stimulus for propagating activity.     

Sympathetic innervation of the ileocecal junction in horses

The distribution and chemical phenotypes of sympathetic and dorsal root ganglion (DRG) neurons innervating the equine ileocecal junction (ICJ) were studied by combining retrograde tracing and immunohistochemistry. Immunoreactivity (IR) for tyrosine hydroxylase (TH), dopamine beta‐hydroxylase (DBH), neuronal nitric oxide synthase (nNOS), calcitonin gene‐related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) was investigated. Sympathetic neurons projecting to the ICJ were distributed within the celiac (CG), cranial mesenteric (CranMG), and caudal mesenteric (CaudMG) ganglia, as well as in the last ganglia of the thoracic sympathetic chain and in the splanchnic ganglia. In the CG and CranMG 91 ± 8% and 93 ± 12% of the neurons innervating the ICJ expressed TH‐ and DBH‐IR, respectively. In the CaudMG 90 ± 15% and 94 ± 5% of ICJ innervating neurons were TH‐ and DBH‐IR, respectively. Sympathetic (TH‐IR) fibers innervated the myenteric and submucosal ganglia, ileal blood vessels, and the muscle layers. They were more concentrated at the ICJ level and were also seen encircling myenteric plexus (MP) and submucosal plexus (SMP) descending neurons that were retrogradely labeled from the ICJ. Among the few retrogradely labeled DRG neurons, nNOS‐, CGRP‐, and SP‐IR nerve cells were observed. Dense networks of CGRP‐, nNOS‐, and SP‐IR varicosities were seen around retrogradely labeled prevertebral ganglia neurons. The CGRP‐IR fibers are probably the endings of neurons projecting from the intestine to the prevertebral ganglia. These findings indicate that this crucial region of the intestinal tract is strongly influenced by the sympathetic system and that sensory information of visceral origin influences the sympathetic control of the ICJ. J. Comp. Neurol. 518:4046–4066, 2010. © 2010 Wiley‐Liss, Inc.     

Spatio-temporal analysis reveals aberrant linkage among sequential propagating pressure wave sequences in patients with symptomatically defined obstructed defecation

Abstract  Available evidence implicates abnormal colonic contractility in patients suffering from constipation. Traditional analysis of colonic manometry focuses on the frequency, extent and amplitude of propagating sequences (PS). We tested the hypotheses that the spatio-temporal linkage among sequential PSs exists throughout the healthy human colon and is disrupted during constipation. In eight patients with severe constipation and eight healthy volunteers, we recorded colonic pressures from 16 regions (caecum–rectum) for 24 h. Sequential PSs were regionally linked if the two PSs originated from different colonic regions but the segments of colon traversed by each PS overlapped. In order to determine whether this linkage occurred by chance, a computer program was used to randomly rearrange all PSs in time. Data were re-analysed to compare regional linkage between randomly re-ordered PSs (expected) and the natural distribution of PSs (observed). In controls the observed regional linkage (82.5 ± 9.0%) was significantly greater than the expected value (60.5 ± 4.3%; P  = 0.0001). In patients the observed and expected regional linkage did not differ. The (observed − expected) delta value of regional linkage in controls was significantly greater than in patients (21.7 ± 8.5% vs −2.3 ± 7.0%; P  = 0.01). Regional linkage among sequential PSs in the healthy colon appears to be a real phenomenon and this linkage is lost in patients with constipation. Regional linkage may be important for normal colonic transit and loss of linkage might have pathophysiological relevance to and provide a useful biomarker of severe constipation.     

Internal anal sphincter relaxation associated with bisacodyl‐induced colonic high amplitude propagating contractions in children with constipation: a colo‐anal reflex?

Background Describe the association of internal anal sphincter (IAS) relaxation with colonic high‐ amplitude peristaltic contractions (HAPCs). Methods Retrospective review of colon manometry tracings of children with constipation to determine the IAS relaxation characteristics associated with HAPC’s (HAPC‐IASR) events and compare them to the those seen during the performance of the anorectal manometry (ARMRAIR) events. Key Results A total of 70 HAPC‐ IASRs were observed in 15 patients, 65 after bisacodyl, two during fasting and three after a meal. In 64% of events, the IAS relaxation started when the HAPC reached left colon and in 36% as proximal as the hepatic flexure. High‐ amplitude peristaltic contraction propagation seems to be important in HAPC‐IASR characteristics; those propagating distal to sigmoid colon demonstrated larger and longer IAS relaxation as well as lower residual pressure, but equivalent resting pressure compared with HAPC’s ending proximal to sigmoid colon. Although IAS resting pressure was comparable for ARM‐RAIRs and HAPC‐IASRs, the duration and magnitude of anal relaxation was higher, and the anal residual pressure was lower in HAPC‐IASRs. Conclusions & Inferences We demonstrated that IAS relaxation in constipated children is associated with HAPCs migrating in the proximal and distal colon; in most cases, starting when peristalsis is migrating through left colon and in an important proportion while migrating proximally. We also demonstrated that HAPC‐IASRs are different from ARM‐RAIRs suggesting a neurally mediated reflex. Finally, the IAS relaxation characteristics are highly dependent on the degree of propagation of HAPCs, which could have important implications in the understanding of defecation disorders.     

Pancolonic spatiotemporal mapping reveals regional deficiencies in,and disorganization of colonic propagating pressure waves in severe constipation

Background The morphology, motor responses and spatiotemporal organization among colonic propagating sequences (PS) have never been defined throughout the entire colon of patients with slow transit constipation (STC). Utilizing the technique of spatiotemporal mapping, we aimed to demonstrate ‘manometric signatures’ that may serve as biomarkers of the disorder. Methods In 14 female patients with scintigraphically confirmed STC, and eight healthy female controls, a silicone catheter with 16 recording sites spanning the colon at 7.5 cm intervals was positioned colonoscopically with the tip clipped to the cecum. Intraluminal pressures were recorded for 24 h. Key Results Pan‐colonic, 24 h, spatiotemporal mapping identified for the first time in STC patients: a marked paucity of propagating pressure waves in the mid‐colon (P = 0.01), as a consequence of a significant (P < 0.0001) decrease in extent of propagation of PS originating in the proximal colon; an increase in frequency of retrograde PS in the proximal colon; a significant reduction in the spatiotemporal organization among PS (P < 0.001); absence of the normal nocturnal suppression of PS. Conclusions & Inferences Pan‐colonic, 24 h, spatiotemporal pressure mapping readily identifies characteristic disorganization among consecutive PS, regions of diminished activity and absent or deficient fundamental motor patterns and responses to physiological stimuli. These features are all likely to be important in the pathophysiology of slow transit constipation.     

Efficacy of the glucagon‐like peptide‐1 agonist exenatide in the treatment of short bowel syndrome

Background Short bowel syndrome (SBS) is a serious clinical disorder characterized by diarrhea and nutritional deprivation. Glucagon‐like peptide‐1 (GLP‐1) is a key hormone, produced by L‐cells in the ileum, that regulates proximal gut transit. When extensive ileal resection occurrs, as in SBS, GLP‐1 levels may be deficient. In this study, we test whether the use of GLP‐1 agonist exenatide can improve the nutritional state and intestinal symptoms of patients with SBS. Methods Five consecutive patients with SBS based on ≤90 cm of small bowel and clinical evidence of nutritional deprivation were selected. Baseline SBS symptoms, demographic and laboratory data were obtained. Antroduodenal manometry was performed on each subject. Each patient was then started on exenatide and over the following month, the baseline parameters were repeated. Key Results The subjects consisted of four males and one female, aged 46–69 years. At baseline, all had severe diarrhea that ranged from 6 to 15 bowel movements per day, often occurring within minutes of eating. After exenatide, all five patients had immediate improvement in bowel frequency and form; bowel movements were no longer meal‐related. Total parenteral nutrition was stopped successfully in three patients. Antroduodenal manometry revealed continuous low amplitude gastric contractions during fasting which completely normalized with exenatide. Conclusions & Inferences Exenatide is a novel and safe treatment option for SBS. It produced substantial improvement in the bowel habits, nutritional status and quality of life of SBS patients. Successful treatment with exenatide may significantly reduce the need for parenteral nutrition and small bowel transplant.     

Twenty-four hour spatiotemporal mapping of colonic propagating sequences provides pathophysiological insight into constipation

Abstract  Colonic propagating sequences (PS)s are a major determinant of luminal propulsion. A global appreciation of spatiotemporal patterning of PSs requires evaluation of 24 h pan-colonic recordings, a difficult task given that PSs are relatively infrequent events that are not uniformly distributed throughout the colon. Here we developed a means of space-time-pressure 'mapping' in a condensed format, 24 h of colonic recording in such a manner that readily permits an overall view of colonic antegrade and retrograde colonic PSs within a single figure. Such graphical representation readily permits appreciation and identification of aberrant patterns in severe constipation and may be an important clinical and research tool in the assessment of colonic motor disorders.     

Anatomical registration and three‐dimensional visualization of low and high‐resolution pan‐colonic manometry recordings

Background Colonic propagating sequences (PS) are important for the movement of colonic content and defecation, and aberrant PS patterning has been associated with slow transit constipation. However, because these motor patterns are typically recorded over long periods (24 h +), the visualization of PS spatiotemporal patterning is difficult. Here, we develop a novel method for displaying pan‐colonic motility patterns. Methods A 3D mesh representing the geometry of the human colon was created as follows: (i) Human colon images from the Visible Human Dataset were digitized to create a 3D data cloud, and (ii) A surface mesh was fitted to the cloud using a least‐squares minimization technique. Colonic manometry catheters were placed in the ascending colon of healthy controls and patients with slow transit constipation (STC), with the aid of a colonoscope. The colonic manometry data were interpolated and mapped to the model according to the following anatomical landmarks: cecum, hepatic flexure, splenic flexure, sigmoid‐descending junction, and anus. Key Results These 3D images clearly and intuitively communicate characteristics of normal and abnormal colonic motility. Specifically we have shown the reduced amplitude of the antegrade propagating pressure waves (PPW) throughout the colon and reduced frequency of PPWs at the mid‐colon in patients with STC. Conclusions and Inferences A novel method for the 3D visualization of PS is presented, providing an intuitive method for representing a large volume of physiological data. These techniques can be used to display frequency, amplitude or velocity data, and will help to convey regions of abnormally in patient populations.     

In vitro and in vivo effects of nitric oxide synthase inhibitors and nitric oxide inactivators on the South American opossum ileocolonic junction*

The potential role of nitrergic nerves in the regulation of the South American (SA) opossum ileocolonic junction (ICJ) function was investigated. In vitro, the effects of nitric oxide (NO) synthase inhibitors and NO inactivators on the non-adrenergic non-cholinergic (NANC) nerve-mediated relaxations of the circular muscle of the SA opossum ICJ were determined by employing isolated strips. Electrical field stimulation (0.2–8.0 Hz) caused frequency-dependent NANC relaxations. Nicotine and ATP also induced concentration dependent NANC relaxations that were abolished by tetrodotoxin (TTX). The relaxation response induced by NANC nerve activation was reduced in a dose dependent manner by NO synthase inhibitors while vasoactive intestinal peptide (VIP) and sodium nitroprusside (SNP) induced relaxations were uninfluenced by these drugs. In vivo, the NO synthase inhibitor, L -NAME, administered into the local artery caused a raise in intraluminal pressure of the ICJ in anaesthetized SA opossums in a L -arginine-preventable manner. Hydroquinone and pyrogallol, while being able to reduce, in a superoxide dimutase (SOD) reversible manner, the relaxations induced by exogenous NO failed to affect the NANC nerve-induced relaxations. Finally, neurones and nerve fibres in the myenteric plexus as well as varicose nerve fibres on the circular smooth layer were positive for NADPH-diaphorase activity. These findings indicate that nitrergic nerves inhibit ICJ circular smooth muscle in vitro and in vivo but cast doubts on the neuromediator being the NO radical.     

Cardiovascular compression of the esophagus and spread of gastro‐esophageal reflux

Background Factors that determine the spread of gastro‐esophageal reflux (GER) along the length of the esophagus are not known. We investigated if cardiovascular (CV) compressions on the esophagus may determine the spread of refluxate into the proximal esophagus. Methods High‐resolution manometry (HRM) and multi‐channel intra‐luminal impedance recording (MIIR) were performed simultaneously in 10 normal subjects in the recumbent and upright positions. Pulsatile pressure increases on the esophagus (marker of CV compression) were identified on the HRM. Spread of refluxate into the esophagus was determined by the MIIR. Key Results Cardiovascular compression zones were observed in the esophagus in 9 out of 10 subjects in recumbent position. Forty percent of GER episodes were limited to the distal esophagus in the recumbent position and CV compression pressure was greater than distal esophageal pressure at the time of GER in all such cases. On the other hand, distal esophageal pressure was greater than CV compression pressure when the refluxate extended into the proximal esophagus. In the upright position, CV compression was less frequent than recumbent position and only 12% of GER episodes were limited to the distal esophagus. Conclusions & Inferences Cardiovascular compression of the esophagus is frequently observed in normal healthy subject and restricts the spread of refluxate into the proximal esophagus.     

Day‐to‐day reproducibility of prolonged ambulatory colonic manometry in healthy subjects

Background Although colonic manometry provides useful information regarding colonic physiology, considerable variability has been reported both for regional motility and manometric patterns. Whether colonic manometry is reproducible is not known. Methods Seven healthy volunteers (three men, four women, mean age = 34 years) underwent two studies of 24‐h ambulatory colonic manometry, each 2 weeks apart. Manometry was performed by placing a six‐sensor solid‐state probe, up to the hepatic flexure and anchored to colonic mucosa. Colonic motility was assessed by the number and area‐under‐curve (AUC) of pressure waves and motility patterns such as high‐amplitude propagating contractions (HAPC). Waking and meal‐induced gastrocolonic responses were also assessed. Paired t‐test was used to examine the reproducibility and intra and interindividual variability. Key Results The number of pressure waves and propagating pressure waves and HAPC, and AUC were similar between the two studies. Diurnal variation, waking and meal‐induced gastrocolonic responses were also reproducible. There was some variability in the incidence of individual colonic motor patterns. Conclusions & Inferences Colonic manometry findings were generally reproducible, particularly for the assessment of key physiologic changes, such as meal‐induced gastrocolonic, HAPC, and waking responses.     

Neurogenic pathways mediating ascending and descending reflexes at the porcine ileocolonic junction

We studied the pharmacology of the neural pathways mediating the responses of ileo‐ and coloileo‐colonic junction (ICJ) to regional distension in ten anaesthetized pigs. Using manometric pullthroughs and a sleeve sensor, we found the ICJ demonstrated sustained tone that was resistant to tetrodotoxin. Ileal distension decreased ICJ pressure by 22.2 ± 10.1% (11.9 ± 2.7–10.1 ± 2.6 mmHg; P=0.002) and colonic distension augmented ICJ pressure by 23.5 ± 8.6% (12.8 ± 1.5–15.6 ± 2.1 mmHg; P=0.02). Bethanecol and Nω‐nitro‐ L ‐arginine methyl ester ( L ‐NAME) increased ICJ pressure (P=0.002, P=0.01, respectively). Sodium nitroprusside and isoproterenol reduced ICJ pressure (P=0.004, P=0.02, respectively). In the presence of L ‐NAME, the early inhibitory ileo‐ICJ response was abolished, while early and late inhibitory responses were abolished by further addition of propranolol but not by the addition of hexamethonium, atropine, prazosin or yohimbine. The excitatory colo‐ICJ response was replaced by inhibition in the presence of L ‐NAME. We concluded that: 1 the porcine ICJ displays myogenic tone which is influenced by excitatory muscarinic and inhibitory nitrergic and beta adrenergic pathways 2 an inhibitory ileo‐sphincteric reflex mediated by nitrergic and beta adrenergic postganglionic neural pathways 3 both excitatory and inhibitory neurogenic colo‐sphincteric reflexes exist, and the excitatory pathway involves nitrergic neurotransmission.     

Comparison of small‐bowel motility of the human jejunum and ileum

Background Knowledge about human cyclic fasting motility (MMC) and the postprandial response is mostly based on manometric findings in the upper small intestine. Hardly any data exist on human ileal motility, as the acquisition of data has been limited by methodological concerns. The aim was to study human jejunal and ileal motility in an optimized manometric setting. Methods Solid‐state 24‐h‐manometry was performed in the jejunum and ileum of healthy individuals, applying a strict protocol for fasting, resting, and the consumption of a standardized meal. Both visual qualitative and validated computerized quantitative contraction and propagation analysis were performed. Key Results MMC occurs in similar frequency in the jejunum and ileum, but it was significantly shorter in the jejunum at night. By many characteristics, ileal motility was less intense and propagative than jejunal: less migrating clustered contractions, and slower propagation velocity and shorter distance in phases II and III, and postprandially – possibly slowing and enhancing nutrient absorption. Prolonged propagated contractions in some individuals were identified as a unique ileal propulsive pattern. Postprandially, an abrupt conversion to a digestive motility pattern occurs simultaneously independent of the region. Conclusions & Inferences We found similar basic phenomena of fasting and postprandial motility in the jejunum and ileum of healthy humans. However, different calibration of propagative and contractile activity and special motor events in the ileum may account for a different physiological role in digestion. Future studies of small‐bowel motility in healthy and diseased subjects focusing on segmental differences of proximal and distal intestine may be rewarded.     

Distention of the colon is associated with initiation of propagated contractions in children

Abstract  The presence of high-amplitude propagating contractions (HAPCs) has been identified as a marker of colonic neuromuscular integrity. The physiologic mechanisms of HAPCs initiation have yet to be determined. Distention secondary to colonic filling has been hypothesized as physiologic initiator. The aim of this study was to study the effect of intraluminal balloon distention in the colon of children with defecatory disorders. Colonic manometry was performed with a polyethylene balloon situated at the proximal end of the catheter, which was placed in the most proximal colonic segment reached during colonoscopy. A stepwise pressure controlled distention of the balloon was performed using barostat computer (10–50 mmHg). Propagated contractions were defined as those that migrated over at least three recording sites. They were divided into HAPCs, amplitude >60 mmHg and low-amplitude propagating contractions (LAPCs), amplitude <60 mmHg. Children with spontaneous HAPCs or HAPCs after bisacodyl provocation were considered to have normal motility. Twenty children completed the study. Among the 14 children with normal colonic motility, balloon distention elicited HAPCs in four and LAPCs in 10 children. No HAPC were elicited in six children with abnormal motility and LAPCs were seen in four of them. The balloon-induced propagated contractions had similar characteristics as those occurring spontaneously and after bisacodyl provocation but the pressure needed to elicit them and their amplitude was inconsistent. These findings suggest that intraluminal distention can trigger propagated contractions in children. This mechanism of action for induction of propagated contractions is not as consistent as the motor response found in response to bisacodyl administration.     

Measurement of acid exposure of proximal esophagus: a better tool for diagnosing non‐erosive reflux disease

Background The sensitivity of 24‐h pH monitoring is poor in non‐erosive reflux disease (NERD). In NERD patients, the proximal extent of acid reflux is one of the main determinants of reflux perception. The present study was aimed to compare the diagnostic accuracy of acid exposure time (AET), at 5 cm above the lower esophageal sphincter, with those at 10 cm and at 3 cm below the upper esophageal sphincter as well as the reproducibility of these parameters. Methods A total of 93 consecutive NERD patients, with typical symptoms responsive to proton pump inhibitor treatment, and 40 controls underwent esophageal manometry and multi‐channel 24‐h pH‐test; 13 patients underwent the same study on two occasions. Symptom association probability (SAP) values were evaluated at each esophageal level. Key Results The ROC curve indicates that the area under the curve was 0.79 at distal (SE = 0.039), 0.87 (SE = 0.032) at proximal (P = 0.029 vs distal), and 0.85 (SE = 0.033) at very proximal esophagus (P = 0.148). AET showed a reproducibility of 61% (Kappa 0.22) at distal esophagus, 77% (Kappa 0.45) at proximal and 53% (Kappa 0.05) at very proximal esophagus. The percentage of patients with a positive SAP was not significantly different when assessed at the distal compared with the proximal esophagus. Conclusions & Inferences In NERD patients, the diagnostic yield of the pH test is significantly improved by the assessment of AET at the proximal esophagus. As this variable seems to be less affected by the day to day variability, it could be considered a reliable and useful diagnostic tool in NERD patients.