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.     

High amplitude propagated contractions

While most colonic motor activity is segmental and non‐propulsive, colonic high amplitude propagated contractions (HAPC) can transfer colonic contents over long distances and often precede defecation. High amplitude propagated contractions occur spontaneously, in response to pharmacological agents or colonic distention. A subset of patients with slow transit constipation have fewer HAPC. In this issue of Neurogastroenterology and Motility, Rodriguez et al. report that anal relaxation during spontaneous and bisacodyl‐induced HAPC exceeds anal relaxation during rectal distention in constipated children undergoing colonic manometry. Moreover, and consistent with a neural mechanism, anal relaxation often precedes arrival of HAPC in the left colon. High amplitude propagated contractions are also used to evaluate the motor response to a meal and pharmacological stimuli (e.g., bisacodyl, neostigmine) and to identify colonic inertia during colonic motility testing in chronic constipation. This editorial comprehensively reviews the characteristics, physiology and pharmacology of HAPC, their assessment by manometry, and relevance to constipation and diarrhea.     

Effect of bowel cleansing on colonic transit in constipation due to slow transit or evacuation disorder

Colon transit time measurement with radio-opaque markers is a method of studying the passage of luminal contents throughout the colon. Overall colonic transit time (CTT), as well as segmental transit times [right (RTT), left (LTT) and rectosigmoid (RSTT)], can be calculated. We hypothesize that CTT is influenced by faecal impaction when the rectum is emptied infrequently. The aim of this study is to investigate the effect of bowel cleansing on colonic transit time in patients with chronic constipation. In 25 women (age 41 years; range 20-65 years) with constipation according to Thompson criteria, CTT measurement was performed in an unprepared situation and repeated after cleansing with 4 L of Klean-Prepreg. Ten healthy female volunteers (age 41 years; range 27-57 years) were used as controls. In constipated patients, CTT decreased from a median 70 h (range 10-130 h) to 48 h (5-94 h) in the cleansed state (P < 0.001). A shortening of transit time was found in all three segments. In 10 patients with slow transit (ST) (CTT > 86 h), CTT decreased from 110 h (range 94-130) to 86 (38-94) (P < 0.001). Five of the 10 patients with ST before bowel cleansing had a CTT below 86 h after cleansing. In female controls, uncleansed CTT and RSTT shortened from 39 h (23 to 62) and 17 h (8-29) to 29 h (17-48) and 10 h (0-20) after bowel cleansing (P=0.058 and P=0.046). Colonic intraluminal contents have a substantial effect on colonic transit. In female controls, bowel cleansing shortened rectosigmoid transit. Women with constipation had faster transit in the cleansed state, however, the distribution of markers was not altered. Despite the effect of bowel cleansing on CTT, it seems unnecessary to prepare the bowel in clinical practice because the differentiation of patients between slow transit constipation and outlet obstruction is not changed. However, because in an infrequent defecation pattern, the influence of faecal impaction is considerable, CTT should be applied with care for critical clinical decisions in the treatment of constipation.     

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 transit time in patients with myelomeningocele

To evaluate colonic motility in patients with myelomeningocele, the transit time of radiopaque markers was studied in 22 patients with myelomeningocele and 22 age and sex matched controls. Mean colonic transit time was significantly longer in patients than in controls (103.2 ± 49 h versus 23.3 ± 13 h; P < 10⁻⁷). Thirteen of 22 patients with myelomeningocele were severely constipated. Six patients had constipation secondary to delayed colonic transit, particularly in the left colon, and seven had increased rectosigmoïd transit. The clinical questionnaire and particularly the frequency of bowel movements did not predict colonic transit. Among 13 patients with increased colonic transit, eight had more than five bowel movements per week and, thus, six of them did not use laxatives or enemas, despite the presence of faecal incontinence. There was no relationship between colonic transit time and the level of the spinal lesion or patient mobility in patients with myelomeningocele. Rectoanal dyssynergia was found in 14 of the 22 patients, but equally often in patients with delayed rectosigmoid transit (4/7) as in the other patients (10/15) (P = ns). Uninhibited detrusor contractions were observed more often in patients with increased colonic transit time than in others (8/12 versus 1/8, P = 0.05). In the absence of a correlation between colonic transit time, clinical symptoms, anorectal motility, level of spinal lesion, patient mobility, evaluation of colonic transit of radiopaque markers should be assessed routinely in all patients with myelomeningocele to plan the most appropriate treatment, mainly in case of unhibited detrusor contractions.     

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.     

Colonic transit time and anorectal manometric anomalies in 19 patients with complete transection of the spinal cord

In order to determine the relative importance of sympathetic and parasympathetic centers in the control of colorectal motility, colonic transit and anorectal motility were studied in 19 patients with complete spinal cord transection: group 1 (n = 5) where transection was above T9; group 2 (n = 6) where transection was between T9 and L2; group 3 (n = 8) where transection involved S2-S4. Colonic transit time was calculated by the radiopaque markers. Methods and results were compared with those of eight controls, all bedridden for non-digestive surgery. Anorectal motility was investigated by anorectal manometry, and results were compared with those of 17 healthy controls. Both mean right and left colonic transit times were not different in the three groups of patients and the bedridden control group. Mean rectosigmoid and total transit time increased in groups 2 and 3. In five patients of group 3 the mean anal canal (lower part) pressure was higher than in controls. Recto-anal inhibitory reflex was present in all patients, but their was no correlation in group 3 between the volume of rectal distension and both amplitude and duration of the recto-anal inhibitory reflex, and in group 1 between rectal distension and the duration of the recto-anal inhibitory reflex. Rectosigmoid transit time increased when sympathetic and parasympathetic spinal centers are injured, suggesting the importance of this extrinsic nervous control; right and left colonic transit are not affected by spinal cord lesion suggesting that the distal colon but not the proximal colon, is under spinal cord nervous control.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Influence of continuous isobaric rectal distension on gastric emptying and small bowel transit in young healthy women

Patients with slow transit constipation frequently have delayed gastric emptying. In animals rectal distensions inhibit gastrointestinal motility. In healthy volunteers isovolumetric rectal distensions delay upper gut transit. The purpose of this study was to determine the effect of continuous isobaric rectal distension on gastric emptying and oro-cecal transit in young females. Using validated 13C octanoic and lactose-[13C] ureide breath tests gastric half-emptying time and oro-cecal transit time for a meal were measured in 12 volunteers. The tests were repeated in randomized order: during isobaric balloon distension and during sham distension. Isobaric rectal distension was applied using a polyethylene bag connected to a barostat. Intraballoon pressure was kept just below the threshold for the urge sensation. Mean gastric half-emptying time during rectal distension (92.3 +/-5.1 min) was significantly higher than during sham distension (78.8 +/- 4 min; P = 0.015). Mean oro-cecal transit time during rectal distension (391.3 +/-29.1 min) and sham distension (328.8 +/- 38.4 min) were not significantly different. In conclusion, these findings indicate that isobaric rectal distension inhibits gastric emptying, but not small bowel transit in young healthy women. Studies in patients with constipation are indicated.     

Therapeutic effects of loxiglumide, a cholecystokinin antagonist, on chronic constipation in elderly patients: a prospective, randomized, double-blind, controlled trial

Severe chronic constipation is a common health problem, particularly among elderly nursing-home patients. Cholecystokinin (CCK) is involved in the regulation of colonic motility, and the blockade of CCK_A receptors with loxiglumide, a potent and highly specific CCK_A antagonist, dramatically accelerates colonic transit time in healthy human volunteers. The effect of loxiglumide on the bowel habits and colonic transit time in 21 chronically constipated nursing-home patients (mean age 83, range 71–89 years) was studied in a randomized, placebo-controlled, double-blind cross-over study. Loxiglumide 800 mg t.i.d. or identical-looking placebo tablets were given orally in sequence with a 7-day washout period in between for 21 days each. The number of spontaneous bowel movements and that of administered enemas was recorded for each 3-week phase. At the end of each treatment period colonic transit time was assessed using radio-opaque markers. Treatment with loxiglumide significantly (P < 0.005) accelerated colonic transit time from 113 ± 6 to 81 ± 10 h. The frequency of weekly bowel movements increased from 3.9 ± 0.5 (placebo) to 4.9 ± 0.5 (loxiglumide) (P < 0.006), while the number of enemas over the 3 weeks decreased from 2.7 ± 0.6 to 1.3 ± 0.4 for placebo and loxiglumide, respectively (P < 0.005). No serious side-effects were observed and there were no signs of exocrine pancreatic insufficiency induced by loxiglumide. The blockade of CCK_A receptors with loxiglumide significantly improves chronic constipation in geriatric patients. Loxiglumide may therefore constitute the prototype of a new class of potent therapeutic agents effective in the treatment of constipation.     

Pilot study of pyridostigmine in constipated patients with autonomic neuropathy

BACKGROUND: The effects of cholinesterase inhibitors, which increase colonic motility in health, on chronic constipation are unknown. Our aims were to evaluate the efficacy of cholinesterase inhibitors for dysautonomia and chronic constipation and to assess whether acute effects could predict the long term response. METHODS: In this single-blind study, 10 patients with autonomic neuropathy and constipation were treated with placebo (2 weeks), followed by an escalating dose of pyridostigmine to the maximum tolerated dose (i.e., 180-540 mg daily) for 6 weeks. Symptoms and gastrointestinal transit were assessed at 2 and 8 weeks. The acute effects of neostigmine on colonic transit and motility were also assessed. RESULTS: At baseline, 4, 6, and 3 patients had delayed gastric, small intestinal, and colonic transit respectively. Pyridostigmine was well tolerated in most patients, improved symptoms in 4 patients, and accelerated the geometric center for colonic transit at 24 h by > or =0.7 unit in 3 patients. The effects of i.v. neostigmine on colonic transit and compliance predicted (P < 0.05) the effects of pyridostigmine on colonic transit. CONCLUSIONS: Pyridostigmine improves colonic transit and symptoms in some patients with autonomic neuropathy and constipation. The motor response to neostigmine predicted the response to oral pyridostigmine.     

Lower functional gastrointestinal disorders: evidence of abnormal colonic transit in a 287 patient cohort

Background Abnormalities of colonic motility were reported in relatively small studies of patients with lower functional gastrointestinal disorders (FGID) including irritable bowel syndrome (IBS). The influence of gender and body mass on the observed motor pathophysiology is unclear. We sought to compare colonic transit in patients within different lower FGID subgroups and healthy controls, controlling for gender and BMI, and to determine whether BMI independently influences colonic motility. Methods We evaluated a scintigraphic gastrointestinal and colonic transit database of 287 lower FGID patients associated with constipation (IBS‐C, or functional constipation, n = 118), diarrhoea (IBS‐D or functional diarrhoea, n = 139) or mixed bowel function (IBS‐M, n = 30) and 170 healthy controls. We measured colon filling at 6 h (CF 6 h), and overall colonic transit at 8, 24 and 48 h. Key Results Colon filling at 6 h did not differentiate health from FGID. Colonic transit was abnormal at 24 h (GC24 of <1.50 or >3.86) in 29.7% of all lower FGID patients. There was a significant overall association between colonic transit and subject group (healthy controls and FGID subgroups) at 8 (P = 0.01), 24 (P < 0.001) and 48 h (P < 0.001) in particular for those with diarrhoea or constipation at 24 and 48 h (P < 0.05), even after adjusting for age, gender and BMI. In addition, BMI was associated with colonic transit after adjusting for age, gender and subject group. Conclusions & Inferences Abnormal transit is documented non‐invasively with scintigraphy in 30% of lower FGID patients; transit measurement may help document pathophysiology and inform selection of therapy in lower FGID.     

Anin vitro electrophysiological study of the colon from patients with idiopathic chronic constipation

Preparations of the circular muscle layer from the sigmoid colon resected from patients with idiopathic chronic constipation were compared, at an electrophysiological level using the sucrose-gap technique, with preparations of the same region of the intestine resected from patients with rectal carcinoma. Non-adrenergic, non-cholinergic inhibitory neuromuscular transmission, represented by inhibitory junction potentials, was present in preparations from both groups. However, the inhibitory response in preparations from constipated patients had a slower or longer time-course than in those from cancer patients. Also, rebound activity following inhibitory transmission was observed in 34% of preparations from constipated patients but was observed in 67% of preparations from cancer patients. Preparations from both groups displayed the same patterns of spontaneous activity and the same proportion of each group was quiescent. The threshold for generation of action potentials and the passive resistance of the smooth muscle membrane were the same in both groups. However, quiescent preparations from constipated patients were less likely to discharge trains of action potentials when the smooth muscle membrane was depolarized than were preparations from cancer patients. These changes in transmission processes and excitability in tissue from constipated patients are discussed in relation to altered states of colonic motility found in people with idiopathic chronic constipation.     

Substance P and vasoactive intestinal peptide are reduced in right transverse colon in pediatric slow‐transit constipation

Background Slow‐transit constipation (STC) is recognized in children but the etiology is unknown. Abnormalities in substance P (SP), vasoactive intestinal peptide (VIP) and nitric oxide (NO) have been implicated. The density of nerve fibers in circular muscle containing these transmitters was examined in colon from children with STC and compared to other pediatric and adult samples. Methods Fluorescence immunohistochemistry using antibodies to NO synthase (NOS), VIP and SP was performed on colonic biopsies (transverse and sigmoid colon) from 33 adults with colorectal cancer, 11 children with normal colonic transit and anorectal retention (NAR) and 51 with chronic constipation and slow motility in the proximal colon (STC). The percentage area of nerve fibers in circular muscle containing each transmitter was quantified in confocal images. Key Results In colon circular muscle, the percentage area of nerve fibers containing NOS > VIP > SP (6 : 2 : 1). Pediatric groups had a higher density of nerve fibers than adults. In pediatric samples, there were no regional differences in NOS and VIP, while SP nerve fiber density was higher in sigmoid than proximal colon. STC children had lower SP and VIP nerve fiber density in the proximal colon than NAR children. Twenty‐three percent of STC children had low SP nerve fiber density. Conclusions & Inferences There are age‐related reductions in nerve fiber density in human colon circular muscle. NOS and VIP do not show regional variations, while SP nerve fiber density is higher in distal colon. 1/3 of pediatric STC patients have low SP or VIP nerve fiber density in proximal colon.     

Constipation in parkinson's disease: Objective assessment and response to psyllium

We evaluated the reliability of patient history and the effect of psyllium on symptoms and colorectal function in 12 patients with Parkinson's disease (PD) and constipation. In all but two, constipation anteceded the development of parkinsonian symptoms. A comparison with prospectively obtained stool diaries confirmed the patients' reported constipation in 7 of the 12 patients. Those patients with confirmed constipation had lower stool weights and reported more straining at stool. Measures of colonic and anorectal function were similar in those who were truly constipated and those who were not. Among those PD subjects with confirmed constipation, psyllium increased stool frequency and weight but did not alter colonic transit or anorectal function. We conclude that prospectively obtained stool diaries should be employed to confirm constipation in PD and that psyllium produces both subjective and objective improvements in constipation related to PD.     

Immunoreactivity for Ano1 detects depletion of Kit‐positive interstitial cells of Cajal in patients with slow transit constipation

Background Depletion of interstitial cells of Cajal (ICC) is associated with several gastrointestinal (GI) motility disorders. Changes in ICC networks are usually detected by immunolabeling for the receptor tyrosine kinase Kit. Ano1 (DOG1 or TMEM16A) was recently described as a marker of ICC in GI tract. Our aim was to determine whether Ano1 immunoreactivity can be used as a reliable marker for ICC in tissues from patients with motility disorders. Methods Four tissues from patients with normal ICC numbers and four tissues from patients with slow transit constipation and loss of Kit‐positive ICC were studied. Interstitial cells of Cajal were detected by double labeling using antisera to Kit and Ano1. Key Results Both the processes and cell bodies of ICC in tissue from controls and slow transit constipation were immunoreactive for Ano1. There was a near complete overlap between Kit and Ano1 immunoreactivity. Tissues from patients with slow transit constipation contained significantly fewer Ano1‐positive ICC than control tissues. The numbers of ICC identified by Ano1 and Kit immunoreactivity were nearly identical across the range of ICC numbers from an average of 1.64 to 7.05 cells per field and correlated with an R² value of 0.99. Conclusions & Inferences Ano1 is a reliable and sensitive marker for detecting changes in ICC networks in humans. Labeling with antibodies selective for Ano1 reproducibly detects depletion of Kit‐positive ICC in tissues from patients with slow transit constipation.     

Rectal sensorimotor characteristics in female patients with idiopathic constipation with or without paradoxical sphincter contraction

Patients with chronic constipation fulfilling the Thompson criteria can show paradoxical sphincter contraction. Aim of this study was to evaluate rectal sensorimotor characteristics in patients with constipation with or without paradoxical sphincter contraction. Thirty female patients with chronic constipation and 22 female controls were investigated with anal manometry and rectal barostat. Paradoxical sphincter contraction was shown with manometry as a paradoxical increase of anal pressure during straining. Visceral sensitivity and compliance were tested by intermittent and continuous pressure-controlled distension. Patients were classified according to their sensations and compliance into normal, hypersensitive, reduced compliant, insensitive or excessive compliant rectum. Postprandial rectal response (PRR) and phasic volume events (PVEs) were registered for 1 h after a 600-kCal meal. Paradoxical sphincter contraction was found in 13 (43%) patients. In these patients, rectal sensitivity scores were higher (P = 0.045) than in patients without paradoxical contractions, but rectal compliance was not different. In 90% of patients an abnormal rectal sensitivity or compliance was found: excessively compliant in 35%, reduced compliant in 10%, hypersensitive in 27% and hyposensitive in 17%. Both patients with constipation (11%; P = 0.042) and controls (25%; P = 0.002) exhibited the presence of a postprandial rectal response. This response was not significantly different between idiopathic constipation, paradoxical sphincter contraction and controls. Patients with rectal hypersensitivity had lower response than other patients (P = 0.04). Patients with constipation had fewer basal PVEs compared controls (P = 0.03). Postprandial PVEs increased in both patients (P = 0.014) and controls (P < 0.001). Postprandial rectal response and PVE were not different in patients with or without paradoxical sphincter contraction. A total of 90% of female patients with idiopathic constipation show an abnormality in rectal sensation or compliance. The postprandial rectal response was comparable between patients with constipation and controls, however, PVEs were diminished. Patients with paradoxical sphincter contraction had higher rectal sensitivity but an unaltered compliance and postprandial rectal response. Future trials should investigate whether the classification of rectal abnormalities in patients with constipation has clinical importance.     

Classification of normal and abnormal colonic motility based on cross‐correlations of pancolonic manometry data

Background Manual analysis of data acquired from manometric studies of colonic motility is laborious, subject to laboratory bias and not specific enough to differentiate all patients from control subjects. Utilizing a cross‐correlation technique, we have developed an automated analysis technique that can reliably differentiate the motor patterns of patients with slow transit constipation (STC) from those recorded in healthy controls. Methods Pancolonic manometric data were recorded from 17 patients with STC and 14 healthy controls. The automated analysis involved calculation of an indicator value derived from cross‐correlations calculated between adjacent recording sites in a manometric trace. The automated technique was conducted on blinded real data sets (observed) and then to determine the likelihood of positive indicator values occurring by chance, the channel number within each individual data set were randomized (expected) and reanalyzed. Key Results In controls, the observed indicator value (3.2 ± 1.4) was significantly greater than that predicted by chance (0.8 ± 1.5; P < 0.0001). In patients, the observed indicator value (?2.7 ± 1.8) did not differ from that predicted by chance (?3.5 ± 1.6; P = 0.1). The indicator value for controls differed significantly from that of patients (P < 0.0001), with all individual patients falling outside of the range of indicator values for controls. Conclusions & Inferences Automated analysis of colonic manometry data using cross‐correlation separated all patients from controls. This automated technique indicates that the contractile motor patterns in STC patients differ from those recorded in healthy controls. The analytical technique may represent a means for defining subtypes of constipation.     

Regional variation in the neurochemical coding of the myenteric plexus of the human colon and changes in patients with slow transit constipation

Abstract There are differences in the structure and function between regions of the colon. In patients with slow transit constipation the activity of all regions is markedly slowed. Counts of colonic neurones in slow transit constipation have been semiquantitative and led to varying results. We have applied new methods of quantification of markers in whole mounts of the colonic myenteric plexus to compare density of innervation between regions and between normal patients and those undergoing resection for severe constipation. Whole mounts of colonic myenteric plexus were made from specimens removed for cancer treatment (controls) and cases of severe constipation. All neurones were labelled by anti‐human neuronal protein antibodies. Neurones synthesizing acetyl choline were labelled for choline acetyltransferase (ChAT) and those for nitric oxide by antisera to nitric oxide synthase (NOS). Four populations of neurones were distinguished and quantified according to the two selective markers, ChAT and NOS. In the normal major populations were NOS alone (51% of ascending colon neurones and 44% of descending colon neurones) and ChAT alone (41% ascending colon, 48% descending colon). Nitric oxide synthase/ChAT and NOS‐/ChAT‐comprised only small populations. In all regions in severe constipation, the percentage of NOS‐only colonic myenteric neurones was raised (54% ascending colon, 49% descending colon) and ChAT only was reduced (36% ascending colon, 42% descending colon). The other populations were not changed. Accurate quantification of neuronal populations in whole mounts of human colon reveals inter‐regional differences in innervation and marked changes in innervation in cases of very severe constipation.     

The effects of methane and hydrogen gases produced by enteric bacteria on ileal motility and colonic transit time

Background Gases produced by intestinal flora may modulate intestinal motor function in healthy individuals as well as those with functional bowel disease. Methane, produced by enteric bacteria in the human gut, is associated with slowed intestinal transit and constipation. The effects of hydrogen, another main gas produced by bacterial fermentation in the gut, on small bowel and colonic motor function remains unrecognized. Therefore, we set out to investigate whether intestinal gases including methane and hydrogen could influence the small bowel motility and colonic transit. Methods Guinea pig ileum was placed in the peristaltic bath with tension transducers attached to measure velocity and amplitude of peristaltic contraction before and after the infusion of control, hydrogen, and methane gases. Also, changes in the intraluminal pressures were monitored before and after the gas infusions. Key Results Methane decreased peristaltic velocity and increased contraction amplitude significantly of guinea pig ileum (P < 0.05). The AUC of intraluminal pressure was significantly increased with methane in guinea pig ileum (P < 0.05). In a second experiment, guinea pig colon was placed in the peristaltic bath to measure transit time before and after control, hydrogen, methane, and methane‐hydrogen mixture gas infusions. Hydrogen shortened colonic transit time by 47% in the proximal colon, and by 10% in the distal colon, when compared with baselines (P < 0.05). Conclusions & Inferences Methane delayed ileal peristaltic conduction velocity by augmenting contractility. Hydrogen shortened colonic transit, and that effect was more prominent in the proximal colon than distal colon.