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.     

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.     

Results of 24-h manometric recording of colonic motor activity with endoluminal instillation of bisacodyl in patients with severe chronic slow transit constipation

The aims of this study were to assess the prevalence of manometric colonic abnormalities and to evaluate the motor effect of intraluminal bisacodyl in a cohort of refractory constipated patients. Twenty-four hour colonic motility recordings were performed in 40 patients referred for a severe intractable chronic constipation. At the end of each recording session the motor effects of the endoluminal instillation of 10 mg bisacodyl were assessed. These patients were compared with 20 healthy subjects. The number of high-amplitude propagating contractions (HAPC) was significantly decreased in patients with slow transit constipation (12 +/- 11.6 vs 1 +/- 8.6, P < 0.001). Based on manometric patterns four groups of patients were isolated. Ten patients had no spontaneous HAPC, no food-induced colonic motor response and significantly lower colonic activity in transverse colon (374 +/- 1220 vs 3249 +/- 3458, P < 0.05). Five patients had significantly increased sigmoid segmental motility (20298 +/- 6364 vs 88780 +/- 3643, P < 0.001) and eight patients had significantly lower number of HAPC without other manometric abnormalities while 17 patients had normal colonic motility recordings. Endoluminal bisacodyl was able to induce HAPCs in all groups of patients. Patients with severe slow transit refractory constipation represented a heterogeneous group and endoluminal bisacodyl was able to promote a propagated motor activity in a majority of patients even in those suspected of having an inert colon.     

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.     

Solid-state vs water-perfused catheters to measure colonic high-amplitude propagating contractions

Background Solid‐state (SS) manometry catheters with portable data loggers offer many potential advantages over traditional water‐perfused (WP) systems, such as prolonged recordings in a more physiologic ambulatory setting and the lack of risk for water overload. The use of SS catheters has not been evaluated in comparison with perfused catheters in children. This study aims to compare data provided by SS and WP catheters in children undergoing colonic manometry studies. Methods A SS catheter and a WP catheter were taped together such that their corresponding sensors were at the same location. Simultaneous recordings were obtained using the SS and WP catheters (both 8 channels, 10 cm apart) in 15 children with severe defecation disorders referred for colonic manometry. Signals were recorded for a minimum of 1 h during fasting, 1 h after ingestion of a meal, and 1 h after the administration of bisacodyl. Solid‐state signals from the data logger were analyzed against the perfused signals. All high‐amplitude propagated contractions (HAPCs), the most recognizable and interpreted colonic motor event, were evaluated for spatial and temporal features including their durations, amplitudes, and propagation velocities. Key Results A total of 107 HAPCs were detected with SS and 91 with WP catheters. All WP‐HAPC were also observed with SS. Linear regression analysis showed that SS catheters tended to give higher readings in the presence of amplitudes <102 mmHg and lower reading with amplitudes >102 mmHg. An opposite trend was found for the duration of contractions. No significant difference was found for HAPC velocity. Conclusions & Inferences SS catheters are more sensitive in recording HAPCs in children with defecation disorders compared with the more traditional WP assembly. There is a difference in measurements of amplitude between the two systems. Solid‐state catheters offer potential advantages over WP catheters in children, being portable, safer to use, and may provide data over a more prolonged period.     

In search of objective manometric criteria for colonic high-amplitude propagated pressure waves

Abstract The aims of this study were to explore all characteristics of high-amplitude propagated contractions (HAPCs) that would allow them to be distinguished from nonHAPC colonic pressure waves, and to develop computer algorithms for automated HAPC detection. Colonic manometry recordings obtained from 24 healthy volunteers were used. Automated analysis was performed to detect propagated pressure waves and to determine their amplitude, duration and area under the curve (AUC). For each of these variables distribution plots were made. Automated HAPC counts were compared to visual counts by experienced investigators. Distribution plots of 141093 colonic pressure waves lacked a bimodal pattern, as was also the case for propagated contractions (n = 8758). With increasing high-amplitude thresholds for HAPC detection, a gradual decrease in the automatically detected HAPC number was observed. These findings precluded determination of a threshold. Taking visually detected HAPCs as reference, amplitude thresholds of 100 mmHg in two channels, and 80 mmHg in one channel yielded the highest sensitivity (92%). In conclusion, objective criteria to distinguish HAPCs from other propagated pressure waves on the basis of their amplitude, duration or AUC do not exist. Automated detection of HAPCs using empirically derived criteria leads to an acceptable degree of correlation with visually detected HAPCs.     

High‐resolution colonic manometry accurately predicts colonic neuromuscular pathological phenotype in pediatric slow transit constipation

Background Severe pediatric slow transit constipation (STC) is commonly due to intrinsic colonic neuromuscular disease. We sought to correlate neuromuscular histological phenotypes in pediatric STC with colonic manometric phenotypes using high‐resolution manometry (HRM). We tested the hypothesis that failure of motor quiescence (FQ) between bisacodyl‐induced high amplitude propagating sequences (HAPSs) might predict neuromuscular pathology. Methods Eighteen children (10 males, median age: 7.5 years) with refractory STC underwent stationary colonic HRM before segmental colonic resection. Six age‐matched constipated children with normal colonic transit served as controls. Colonic resection specimens underwent histopathological analysis. Conventional manometric parameters and area under the curve (AUC) during a 1‐min period following bisacodyl‐induced HAPSs [PBAUC₁], as measure of FQ, were calculated. Key Results Numbers of postbisacodyl HAPSs in descending and sigmoid segments were lower in patients than controls (P < 0.01, respectively). Low amplitude propagating sequences (LAPSs) were common prebisacodyl in controls and rare in STC (P < 0.001), whereas postbisacodyl LAPS were more common in STC (P < 0.001). Postbisacodyl, both retrograde propagating contractions and bursts of contractions were present in STC patients only (P < 0.001 and P < 0.01). Postbisacodyl simultaneous pressurization was seen only in STC (P < 0.05 and P < 0.001, in descending and rectosigmoid segments). Histological abnormalities were present in 17/18. Fourteen were neurogenic, one neuro‐myogenic, and two myogenic. In segments with HAPS, PBAUC₁ was predictive of colonic neuropathy using a cutoff of 205 mmHg.s^‐1 (Sensitivity 100%, specificity 86%, PPV92%, NPV100%). Conclusions & Inferences PBAUC₁ is increased in multiple colonic segments in neuropathic pediatric STC and constitutes a sensitive and specific biomarker of neuropathy.     

Prolonged stationary colonic motility recording in seven patients with severe constipation secondary to antidepressants

The aim of this study was to determine whether the colonic motor profile of seven patients with constipation secondary to antidepressants differed from the motility of seven patients with idiopathic constipation and seven healthy volunteers. All constipated patients had very severe constipation. Colonic manometric recordings were performed for 24 h. The number of high amplitude propagating contractions (HAPC) was lower in the two groups of constipated patients than in controls. No HAPC were observed in 5/7 patients with constipation secondary to antidepressants and in 1/7 patients with idiopathic constipation. The overall area under the curve (AUC) in the left colon was lower in the two constipated patient groups than in controls. AUC increased after a 1000-kcal standard meal given at noon in controls but not in the two groups of constipated patients. In conclusion, in patients with constipation secondary to antidepressants, the overall AUC was as poor as in patients with idiopathic constipation, and no colonic response to eating was observed. Moreover, the number of HAPC was more markedly decreased in patients with constipation secondary to antidepressants than in patients with idiopathic constipation.     

Colonic motor activity in slow-transit idiopathic constipation as identified by 24-h pancolonic ambulatory manometry

Colorectal motor activity in slow-transit idiopathic constipation has not been fully evaluated under physiological conditions. The aim of this study was to evaluate colorectal motor activity in chronic idiopathic constipation using 24-h ambulant pancolonic manometry. Ten healthy volunteers (six females) 19-31 years of age, and eight females 25-46 years of age with slow-transit idiopathic constipation were studied. Motor activity was measured using two custom-made silicone-coated catheters, each with five solid-state pressure transducers. Bowel preparation or sedation was not used. Frequency of high-amplitude propagated contractions was reduced in chronic idiopathic constipation, median 1.9/24 h vs 6/24 h (P = 0.01). Contractile frequency of low-amplitude complexes was reduced throughout the colon in slow-transit idiopathic constipation (P < 0.0001). The interval between contractile complexes was reduced in the transverse colon and splenic flexure (P < 0.0001). This study demonstrates that colonic motor activity is abnormal in slow-transit idiopathic constipation; decreased motor activity leads to a reduction in propulsion of intraluminal contents.     

Lesioning of TRPV1 expressing primary afferent neurons prevents PAR-2 induced motility, but not mechanical hypersensitivity in the rat colon

Background Proteinase activated receptor 2 (PAR‐2) is expressed by many neurons in the colon, including primary afferent neurons that co‐express transient receptor potential vanilloid 1 (TRPV1). Activation of PAR‐2 receptors was previously found to enhance colonic motility, increase secretion and produce hypersensitivity to mechanical stimuli. This study examined the functional role of TRPV1/PAR‐2 expressing neurons that innervate the colon by lesioning TRPV1 bearing neurons with the highly selective and potent TRPV1 agonist resiniferatoxin. Methods Colonic motility in response to PAR‐2 activation was evaluated in vitro using isolated segments of descending colon and in vivo using manometry. Colonic mechanical nociceptive thresholds were measured using colorectal distension. Transient receptor potential vanilloid 1 expressing neurons were selectively lesioned with resiniferatoxin. Key Results In vitro, the PAR‐2 agonists, trypsin and SLIGRL did not alter contractions of colon segments when applied alone, however, the agents enhanced acetylcholine stimulated contraction. In vivo, PAR‐2 agonists administered intraluminally induced contractions of the colon and produced hypersensitivity to colorectal distention. The PAR‐2 agonist enhancement of colonic contraction was eliminated when TRPV1 expressing neurons were lesioned with resiniferatoxin, but the PAR‐2 agonist induced hypersensitivity remained in the lesioned animals. Conclusions & Inferences Our findings indicate that TRPV1/PAR‐2 expressing primary afferent neurons mediate an extrinsic motor reflex pathway in the colon. These data, coupled with our previous studies, also indicate that the recently described colospinal afferent neurons are nociceptive, suggesting that these neurons may be useful targets for the pharmacological control of pain in diseases such as irritable bowel syndrome.     

Periodic colonic motor activity identified by 24-h pancolonic ambulatory manometry in humans

The pattern of colonic motor activity in healthy humans has not been fully elucidated to date. The aim of this study was to evaluate colorectal motor activity employing 24-h ambulant pancolonic manometry. Ten healthy volunteers (6F, 4M), aged 19-31 years were studied. Motor activity was measured using two custom-made silicone coated catheters, each with five solid-state pressure transducers. No bowel preparation or sedation was used. The study period was 24 h. A total of 232 h of recording was obtained. Sixty-three high amplitude propagated contractions were observed, median six per 24-h period. Low-amplitude colonic contractile activity showed regional and diurnal variations. Frequency of contraction was highest in the right colon [median 5.26 cpm (cycles per minute)], and transverse colon and splenic flexure (median 5.15 cpm). The interval between colonic motor complexes was shortest in the transverse colon and splenic flexure. This study introduces a new technique for the evaluation of colorectal motor activity. Subjects were studied in an ambulant setting in their own environment ensuring that this method of study is as physiological as possible. This study demonstrates that colonic motor activity has two main components: high amplitude propagated contractions and low amplitude colonic contractile activity.     

Factors associated with successful decrease and discontinuation of antegrade continence enemas (ACE) in children with defecation disorders: a study evaluating the effect of ACE on colon motility

Background Antegrade continence enemas (ACE) have been used in the treatment of defecation disorders in children; little is known on their effect on colon motility and the utility of the colon manometry (CM) predicting long‐term ACE outcomes. Methods Retrospective review of children with constipation undergoing CM before and after ACE to evaluate CM changes and their utility on predicting ACE outcome. Key Results A total of 40 patients (mean age 8.8 SD 3 years and 53% female patients) were included; 39 of 40 responded to the ACE. Of these 39, 14 (36%) were dependent and 25 (64%) had decreased it (11 of those or 28% discontinued it). On repeat CM we found a significant increase in the fasting (P < 0.01) and postprandial (P = 0.03) motility index, number of bisacodyl‐induced high amplitude propagating contractions (HAPCs) (P = 0.03), and total HAPCs (P = 0.02). Gastrocolonic response to a meal, propagation and normalization of HAPCs improved in 28%, 58%, and 33%, respectively, with CM normalizing in 33% of patients. The baseline CM did not predict ACE outcome. The presence of normal HAPCs on the repeat CM was associated with ACE decrease. Progression and normalization of HAPCs (P = 0.01 and 0.02, respectively) and CM normalization (P = 0.01) on repeat CM were individually associated with ACE decrease. No CM change was associated with ACE discontinuation. Multivariate analysis showed that older age and HAPC normalization on CM predict ACE decrease and older age is the only predictor for ACE discontinuation. Conclusions & Inferences Colon motility improves after ACE and the changes on the repeat CM may assist in predicting ACE outcome.     

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.     

The effect of standard compared to enhanced instruction and verbal feedback on anorectal manometry measurements

Background Guidelines recommend instruction and motivation during anorectal manometry; however, its impact on findings has not been reported. This study assessed the effects of standard versus enhanced instruction and verbal feedback on the results of anorectal manometry. Methods High‐resolution manometry was performed by a solid‐state catheter with 10 circumferential sensors at 6 mm separation across the anal canal and two rectal sensors. Measurements were acquired first with standard instruction and then with enhanced instruction and verbal feedback. On both occasions, squeeze pressure and duration during three voluntary contractions and intra‐rectal pressure and recto‐anal pressure gradient (RAPG) during three attempts at simulated defecation were assessed. Key Results A total of 70 consecutive patients (54 female; age 25–82 years) referred for investigation of fecal incontinence (n = 31), constipation, and related disorders of defecation (n = 39) were studied. Enhanced instruction and verbal feedback increased maximum squeeze pressure (Δ10 ± 28.5 mmHg; P < 0.0038) and duration of contraction (Δ3 ± 4 s; P < 0.0001). During simulated defecation, it increased intra‐rectal pressure (Δ12 ± 14 mmHg; P < 0.003) and RAPG (Δ11 ± 20 mmHg; P < 0.0001). Using standard diagnostic criteria, the intervention changed manometric findings from locally validated ‘pathologic’ to ‘normal’ values in 14/31 patients with incontinence and 12/39 with disorders of defecation. Conclusions & Inferences Enhanced instruction and verbal feedback significantly improved voluntary anorectal functions and resulted in a clinically relevant change of manometric diagnosis in some patients. Effective explanation of procedures and motivation during manometry is required to ensure consistent results and to provide an accurate representation of patient ability to retain continence and evacuate stool.     

High‐resolution manometry changes our views of gastrointestinal motility

High‐resolution manometry using catheters with 36 solid‐state sensors spaced 1 cm apart has already become an established technique for esophageal manometry where it has replaced water‐perfused and station pull‐through manometry. Spatiotemporal plots with color coding of pressure have greatly facilitated the analysis of esophageal peristalsis. Although suitable for the length of the esophagus, the solid‐state catheter is insufficient for the study of longer segments of the gastrointestinal tract. A new technique with fiber‐optic sensors has made it possible to construct catheters with 72–144 sensors. Studies of colonic motility have revealed that the most common motor pattern of the colon is a peristaltic contraction that travels 7–10 cm in the retrograde direction. Earlier studies using low‐resolution manometry with 7–45 cm between sensors led us to erroneous conclusions regarding direction and frequency of contractions and they largely missed both antegrade and retrograde contractions traveling short distances. Fiber‐optic high‐resolution manometry holds promise for greatly improving our understanding of gut motor physiology and hopefully also our understanding of patients with symptoms of disordered gut motility.     

Guanylate cyclase C‐mediated antinociceptive effects of linaclotide in rodent models of visceral pain

Background Linaclotide is a novel, orally administered investigational drug currently in clinical development for the treatment of constipation‐predominant irritable bowel syndrome (IBS‐C) and chronic idiopathic constipation. Visceral hyperalgesia is a major pathophysiological mechanism in IBS‐C. Therefore, we investigated the anti‐nociceptive properties of linaclotide in rodent models of inflammatory and non‐inflammatory visceral pain and determined whether these pharmacological effects are linked to the activation of guanylate cyclase C (GC‐C). Methods Orally administered linaclotide was evaluated in non‐inflammatory acute partial restraint stress (PRS) and acute water avoidance stress (WAS) models in Wistar rats, and in a trinitrobenzene sulfonic acid (TNBS)‐induced inflammatory model in Wistar rats and GC‐C null mice. Key Results In TNBS‐induced colonic allodynia, linaclotide significantly decreased the number of abdominal contractions in response to colorectal distension without affecting the colonic wall elasticity change in response to distending pressures after TNBS. However, linaclotide had no effect on visceral sensitivity under basal conditions. In addition, linaclotide significantly decreased colonic hypersensitivity in the PRS and WAS models. In wild type (wt) and GC‐C null mice, the instillation of TNBS induced similar hyperalgesia and allodynia. However, in post‐inflammatory conditions linaclotide significantly reduced hypersensitivity only in wt mice, but not in GC‐C null mice. Conclusions & Inferences These findings indicate that linaclotide has potent anti‐nociceptive effects in several mechanistically different rodent models of visceral hypersensitivity and that these pharmacological properties of linaclotide are exerted through the activation of the GC‐C receptor. Therefore, linaclotide may be capable of decreasing abdominal pain in patients suffering from IBS‐C.     

Does magnetic stimulation of sacral nerve roots modify colonic motility? Results of a randomized double‐blind sham‐controlled study

Abstract  Although sacral nerve root stimulation (SNS) can result in a symptomatic improvement of faecal incontinence, the mechanism of action remains unknown. The aim of this study was to assess whether short-term magnetic SNS can inhibit pharmacologically induced propulsive colonic contractions. Twelve healthy volunteers (median age: 43.5 years old) were studied on two separate occasions and randomized into either active (15 Hz, 100% output intensity for 5 s min⁻¹ for 30 min) or sham rapid rate lumbosacral magnetic stimulation (rLSMS). Colorectal motility was recorded with a manometric catheter located at the most proximal transducer in the left colon and the most distal, in the rectum. Colonic contractions were provoked by instilling Bisacodyl. The effects of rLSMS on colonic, sigmoid and rectal contractions were monitored and recorded after Bisacodyl instillation. The appearance of high-amplitude contractions propagated or not (HAC/HAPC) provoked by Bisacodyl instillation was significantly delayed during active compared to sham stimulation ( P  = 0.03). There was no difference in the characteristics of HAC/HAPC (i.e. frequency, amplitude, duration, velocity of propagation) or the motility index with active or sham stimulation. The perception of urgency tended to be decreased with rLSMS following Bisacodyl instillation. The catheter was expulsed within a median of 16.5 min (range 8–39) after Bisacodyl administration during active stimulation compared to 14 min (range 5–40) during sham stimulation ( P  = 0.03). This study suggests that rLSMS could delay the appearance of the first Bisacodyl-induced colonic contractions.     

Multiple rapid swallowing: a complementary test during standard oesophageal manometry

Abstract  Multiple rapid swallowing (MRS) stimulates neural inhibition resulting in abolition of contractions in the oesophageal body (OB) and complete lower oesophageal sphincter (LOS) relaxation which is followed by peristalsis and LOS contraction. The aim of this study was to evaluate the yield of MRS to detect abnormalities in inhibitory or excitatory oesophageal mechanisms in patients with oesophageal symptoms and either normal standard manometry or ineffective oesophageal motility (IOM). MRS (five water swallows, 2 mL, separated by 2–3 s) was evaluated in 23 healthy subjects, 109 symptomatic patients with normal standard sleeve manometry and in 48 patients with IOM. Healthy subjects had complete inhibition of OB motility during MRS and a strong motor response after MRS, i.e. amplitude of OB contractions in the oesophageal body and LOS tone being higher than after single swallows. Almost 70% of patients with oesophageal symptoms and normal manometry had abnormal MRS, mainly consistent on inability to increase amplitude of OB contractions after MRS. Nearly, half of the patients with IOM were able to normalize OB contractions after MRS. MRS is a simple complementary test that can be added to standard oesophageal manometry. Two-thirds of patients with normal manometry show abnormal MRS that could potentially underlie their symptoms. A normal response to MRS in patients with severe IOM might be used to predict response to prokinetic treatment.     

Characterization of colonic motor activity in conscious dogs

Diurnal changes in canine colonic motility were investigated by means of chronically implanted force transducers. A characteristic of the colonic motor profile in the fasted state was the occurrence of colonic motor complexes consisting of tonic contractions superimposed with phasic ones. On feeding, motor complexes were immediately induced in the whole colon and continued to occur at significantly shorter intervals than those in the fasted state, but the duration and the amplitude of the colonic motor complexes were not affected by feeding. This increased activity period lasted for 8–16 h after feeding, and 83.3% of the defecations were observed in this period. Of the defecations 33% occurred in the first 2 h after feeding (P < 0.05). More than 80% of the giant migrating contractions associated with defecation propagated from the middle to the distal colon, and the start of faeces evacuation coincided with the end of the relaxation period of the distal colon preceding the arrival of the giant migrating contractions. More than 90% of the giant migrating contractions not associated with defecation migrated from the proximal to the middle colon. More than 60% of the colonic motor complexes migrated in an aboral direction and about 18% of them in an oral direction. These results suggest that (1) defecations tend to occur immediately after feeding; (2) the regional distribution of giant migrating contractions was different between those associated and not associated with defecation.