Comparative analysis of phase III migrating motor complexes in stomach and small bowel using wireless motility capsule and antroduodenal manometry

Background Assessment of phase III MMC is often not performed due to the invasive nature of antroduodenal manometry used to detect it. The aim of the study was to evaluate the ability of wireless motility capsule (WMC) to detect phase III MMC and correlate it with the simultaneous measurements by antroduodenal manometry (ADM). Methods Eighteen patients underwent simultaneous ADM and WMC. MMCs were identified first on ADM and then correlated with WMC events occurring simultaneously. Frequency of contractions per min, AUC, MI, and criteria for amplitude thresholds of contractions representing MCCs on WMC tracings were defined. Key Results In 18 patients, a total of 29 MMCs were recorded by ADM. WMC detected 86% of MMC events measured by ADM. Hundred percent (10/10) of MMCs in stomach were detected by WMC, whereas 79% (15/19) of MMCs were detected in SB. The sensitivity and specificity of WMC high amplitude contractions to represent phase III MMC were 90% and 71.8% in the stomach; 73.7% and 84.7% in SB, respectively, and negative predictive value was 99.9% in both regions. Conclusions & Inferences Wireless motility capsule was able to detect the phase III MMCs as the high amplitude contractions with good fidelity. WMC does not detect the propagation of MMC. Using the pressure thresholds, WMC can detect high amplitude contraction representing phase III MMC with favorable sensitivity/specificity profile and 99.9% negative predictive value. This observation may have clinical significance, as the absence of high amplitude contractions recorded by WMC during fasting state suggests absence of MMCs.     

Difficulty in estimating localized bowel contraction by colonic manometry: a simultaneous recording of intraluminal pressure and luminal calibre

To examine whether or not intraluminal pressure changes at a site in the human colon reflect with fidelity the local bowel wall contractions or relaxation, endoscopic recording of the changes in colonic calibre as a parameter of the motor events with simultaneous manometry was performed at a fixed site in a prepared sigmoid colon during the interdigestive state. In four of the 12 subjects, a total of 20 phasic pressure waves with an amplitude of 13–22 mmHg and a duration of 13–18 sec were obtained in a 20 min recording session. Eighteen of the 20 phasic pressure waves (90%) were associated not with a decrease (contraction) but with an increase in the calibre (relaxation). The pressure change began 0.2–8.4 sec (mean: 4.5 sec) behind and ended ? 1.8 to 8 sec (mean: 3.5 sec) ahead of the calibre change. In the other eight subjects, no phasic pressure change was recorded in the presence of an overt calibre change. We conclude that manometric phasic pressure change recorded at a site in the empty human colon is not necessarily correlated with the localized contractile activity. Extrapolation of pressure profiles in the colon to motor events at the manometric site should be cautious.     

Abnormal small bowel motility in patients with hereditary transthyretin amyloidosis

Background

Gastrointestinal complications are common in hereditary transthyretin amyloid (ATTRm) amyloidosis. The underlying mechanisms have not been fully elucidated, and the patients’ small bowel function remains largely unexplored. The aim of the present study was to compare the small bowel motility in ATTRm amyloidosis patients with that in non‐amyloidosis patient controls.

Methods

ATTRm amyloidosis patients undergoing evaluation for liver transplantation were consecutively investigated with 24‐hour duodenojejunal manometry (n = 19). The somatostatin analogue octreotide was used to induce fasting motility. Patients with age at onset of ≥50 years were defined as late‐onset cases. For each patient, three age‐ and sex‐matched patient controls (n = 57) were selected from the total pool of investigated patients.

Key Results

Manometry was judged as abnormal in 58% of the patients and in 26% of the patient controls (P = .01). Patients displayed significantly more daytime phase III migrating motor complexes than patient controls (median 4 vs 2, P < .01), and had a higher frequency of low‐amplitude complexes (16% vs 4%; however, this difference did not reach statistical significance, P = .10). Furthermore, late‐onset patients showed a delay in octreotide response (5.4 vs 3.8 minutes, P < .01), but this was not observed for early‐onset patients or within the control group.

Conclusions and Inferences

Patients with ATTRm amyloidosis displayed abnormalities in their small bowel motility more frequently than non‐amyloidosis patient controls, and the manometric pattern was probably best consistent with a combined neuromyopathic disorder. The delayed octreotide response in late‐onset patients warrants further investigation.     

Motility of the oesophagus and small bowel in adults treated for Hirschsprung’s disease during early childhood

Background Dysmotility of the upper gastrointestinal (GI) tract has been reported in children with Hirschsprung’s disease (HD). In the present study, motility of the oesophagus and the small bowel was studied in adults treated for HD during early childhood to elucidate whether there are alterations in motility of the upper GI tract in this patient group. [Correction added after online publication 15 Sep: The preceding sentence has been rephrased for better clarity.] Methods Ambulatory small bowel manometry with recording sites in duodenum/jejunum was performed in 16 adult patients with surgically treated HD and 17 healthy controls. In addition, oesophageal manometry was performed with station pull‐through technique. Key Results The essential patterns of small bowel motility were recognized in all patients and controls. During fasting, phase III of the migrating motor complex (MMC) was more prominent in patients with HD than in controls when accounting for duration and propagation velocity (P = 0.006). Phase I of the MMC was of shorter duration (P = 0.008), and phase II tended to be of longer duration (P = 0.05) in the patients. During daytime fasting, propagated clustered contractions (PCCs) were more frequent in the patients (P = 0.01). Postprandially, the patients demonstrated a higher contractile frequency (P = 0.02), a shorter duration of contractions (P = 0.008) and more frequent PCCs (P < 0.001). The patients had normal oesophageal motility. Conclusions & Inferences This study demonstrates that adult patients with HD have preserved essential patterns of oesophageal and small bowel motility. However, abnormalities mainly characterized by increased contractile activity of the small bowel during fasting and postprandially are evident. These findings indicate alterations in neuronal control of motility and persistent involvement of the upper GI tract in this disease.     

Motility of the left colon in children and adolescents with functional constpation; a retrospective comparison between solid‐state and water‐perfused colonic manometry

Background

Using water‐perfused (WP) high‐resolution manometry, we recently demonstrated that children with functional constipation (FC) lacked the postprandial increase in distal colonic cyclic motor patterns that was observed in healthy adults. Our aim was to determine if similar results could be detected using a solid‐state (SS) manometry catheter.

Methods

We performed a retrospective analysis of 19 children with FC (median age 11.1 years, 58% male) who underwent colonic manometry with a SS catheter (36 sensors, 3 cm apart). Data were compared with previously published data using a WP catheter (36 sensors, 1.5 cm apart) recorded from 18 children with FC (median age 15 years; 28% male).

Key Results

The cyclic motor patterns recorded by the SS catheter did not differ from those previously recorded by the WP catheter. There was no detected increase in this activity in response to the meal in either group. Long‐single motor patterns were recorded in most patients (n = 16, 84%) with the SS catheter. The number of these events did not differ from the WP recordings. In the SS data, HAPCs were observed in 4 children prior to the meal, in 5 after the meal. This did not differ significantly from the WP data.

Conclusions & Inferences

These data recorded by SS manometry did not differ from WP manometry data. Regardless of the catheter used, both studies revealed an abnormal colonic response to a meal, indicating a pathology which is not related to the catheter used to record these data.     

Progressive muscular relaxation and motility of the small intestine: studies in normal subjects and patients with irritable bowel syndrome

Recordings of fasting duodenojejunal motor activity were obtained during a controlled 20-min period of psychological relaxation in 10 patients with irritable bowel syndrome (IBS) and 10 healthy subjects. The IBS group showed a significant decline in their level of arousal (on both cardiovascular and subjective measures) in response to relaxation; such alterations were minimal in the control group. Both groups, however, demonstrated significant inhibition of phase 2 activity (motility index, contractile frequency and amplitude) of the migrating motor complex in response to relaxation, and the magnitude of the response did not differ between the two groups. Clustered contractile activity present in 4 IBS patients was also suppressed during the relaxation period. There were no correlations between changes in the level of arousal and the degree of motor suppression in either IBS patients or controls. These findings demonstrate that psychological relaxation therapy can profoundly influence patterns of small bowel motility, and shed light on the mechanisms by which psychological intervention therapy appears to be effective in IBS.     

High interdigestive and postprandial motilin levels in patients with the irritable bowel syndrome

Motilin shows cyclic variation with the different phases of the migrating motor complex (MMC). Altered motilin levels have been found in irritable bowel syndrome (IBS) patients, but in these studies motilin levels were analysed without the knowledge of the phases of MMC. We included 13 healthy controls (HC) and 24 patients with IBS [12 diarrhoea-predominant (IBS-D) and 12 constipation-predominant (IBS-C)]. We performed interdigestive and postprandial antroduodenojejunal manometry and blood samples for analysis of motilin were drawn. Group differences in plasma levels of motilin were analysed during mid-phase II, just before the start of phase III (pre-III), during phase I, immediately before the meal and 30 and 60 min after the 500 kcal mixed meal. Higher motilin levels were observed in IBS vs HC in both the interdigestive and postprandial periods (P < 0.05). No significant differences between IBS-C and IBS-D were observed. The cyclic variation of motilin during MMC and the meal response was similar in IBS and controls. IBS patients, irrespective of the predominant bowel habit, demonstrate higher motilin levels than HCs in all phases of the MMC and also after a meal. These findings may bear some pathophysiological importance in IBS and relate to the gastrointestinal dysmotility often seen in these patients.     

Randomized pharmacodynamic and pharmacogenetic trial of dronabinol effects on colon transit in irritable bowel syndrome-diarrhea

Background Genetic variation in endocannabinoid metabolism is associated with colonic transit in irritable bowel syndrome (IBS) with diarrhea (IBS‐D). The nonselective cannabinoid (CB) receptor agonist, dronabinol (DRO), reduced fasting colonic motility in nonconstipated IBS. FAAH and CNR1 variants influenced DRO’s effects on colonic motility. Our aims were: (i) to compare dose‐related effects of DRO to placebo (PLA) on gut transit in IBS‐D, and (ii) to examine influence of genetic variations in CB mechanisms on DRO’s transit effects. Methods Thirty‐six IBS‐D volunteers were randomized (double‐blind, concealed allocation) to twice per day PLA (n = 13), DRO 2.5 mg (n = 10), or DRO 5 mg (n = 13) for 2 days. We assessed gastric, small bowel, and colonic transit by validated radioscintigraphy and genotyped the single nucleotide polymorphisms CNR1 rs806378 and FAAH rs324420. Data analysis utilized a dominant genetic model. Key Results Overall treatment effects of DRO on gastric, small bowel, or colonic transit were not detected. CNR1 rs806378 CT/TT was associated with a modest delay in colonic transit at 24 h compared with CC (P = 0.13 for differential treatment effects on postminus pretreatment changes in colonic transit by genotype). No significant interaction of treatment with FAAH rs324420 was detected. Conclusions & Inferences Overall, DRO 2.5 or 5 mg twice per day for 2 days had no effect on gut transit in IBS‐D. There appears to be a treatment‐by‐genotype effect, whereby DRO preferentially delays colonic transit in those with the CNR1 rs806378 CT/TT genotypes. Further study of CB pharmacogenetics may help identify a subset of IBS‐D patients most likely to benefit from CB agonist therapy.     

Sigmoid-colonic motility in health and irritable bowel syndrome: a role for 5-hydroxytryptamine

Abstract Evidence suggests that sigmoid-colonic motility is increased in patients with irritable bowel syndrome (IBS). 5-Hydroxytryptamine (5-HT) plays a role in the control of motility, but its involvement in the dysmotility seen in IBS remains unclear. To investigate the relationship between platelet depleted plasma 5-HT (PDP 5-HT) concentration and sigmoid-colonic motility in patients with IBS and healthy volunteers. Pre- and postprandial PDP 5-HT concentrations were assessed while recording sigmoid-colonic motility in 35 IBS patients (aged 19-53 years, eight male) and 16 healthy volunteers (aged 18-39 years, six male). Motility was recorded using a five-channel solid-state catheter introduced to a depth of 35 cm into an unprepared bowel. 5-Hydroxytryptamine concentration was measured by reverse-phase HPLC with fluorimetric detection. Irritable bowel syndrome patients had elevated concentrations of PDP 5-HT under fasting (P < 0.004) and fed (P = 0.079) conditions compared with controls. Likewise, they exhibited increased sigmoid-colonic motility under fasting (activity index: P < 0.02) and fed (P < 0.05) conditions compared with controls. Platelet depleted plasma 5-HT concentration positively correlated with colonic activity index under both fasting (r = 0.402; P = 0.003) and fed (r = 0.439; P = 0.001) conditions. These data show a possible relationship between endogenous concentrations of 5-HT and sigmoid-colonic motility recorded in both IBS and healthy subjects.