Phil Dinning

Sympathetic Pathways Target Cholinergic Neurons in the Human Colonic Myenteric Plexus

Publisher: Frontiers Media SA

Date: 17-03-2022

DOI: 10.3389/FNINS.2022.863662

Abstract: The sympathetic nervous system inhibits human colonic motility largely by effects on enteric neurons. Noradrenergic axons, which branch extensively in the myenteric plexus, are integral to this modulatory role, but whether they contact specific types of enteric neurons is unknown. The purpose of this study was to determine the association of noradrenergic varicosities with types of enteric neurons. Human colonic tissue from seven patients was fixed and dissected prior to multi-layer immunohistochemistry for human RNA binding proteins C and D (HuC/D) (pan-neuronal cell body labelling), tyrosine hydroxylase (TH, catecholaminergic labelling), Enkephalin (ENK), choline acetyltransferase (ChAT, cholinergic labelling) and/or nitric oxide synthase (NOS, nitrergic labelling) and imaged using confocal microscopy. TH-immunoreactive varicose nerve endings and myenteric cell bodies were reconstructed as three dimensional digital images. Data was exported to a purpose-built software package which quantified the density of varicosities close to the surface of each myenteric cell body. TH-immunoreactive varicosities had a greater mean density within 1 μm of the surface of ChAT +/NOS− nerve cell bodies compared with ChAT−/NOS + cell bodies. Similarly, ENK-immunoreactive varicosities also had a greater mean density close to ChAT +/NOS− cell bodies compared with ChAT−/NOS + cells. A method for quantifying close associations between varicosities and nerve cell bodies was developed. Sympathetic axons in the myenteric plexus preferentially target cholinergic excitatory cells compared to nitrergic neurons (which are largely inhibitory). This connectivity is likely to be involved in inhibitory modulation of human colonic motility by the sympathetic nervous system.

Restoration of normal colonic motor patterns and meal responses after distal colorectal resection

Publisher: Oxford University Press (OUP)

Date: 18-01-2016

DOI: 10.1002/BJS.10074

Abstract: Colorectal resections alter colonic motility, including disruption of control by neural or bioelectrical cell networks. The long-term impact of surgical resections and anastomoses on colonic motor patterns has, however, never been assessed accurately. Fibreoptic high-resolution colonic manometry was employed to define motility in patients who had undergone distal colorectal resection. Recruited patients had undergone distal colorectal resections more than 12 months previously, and had normal bowel function. Manometry was performed in the distal colon (36 sensors 1-cm intervals), with 2-h recordings taken before and after a meal, with comparison to controls. Analysis quantified all propagating events and frequencies (cyclical, short single, and long single motor patterns), including across anastomoses. Fifteen patients and 12 controls were recruited into the study. Coordinated propagating events directly traversed the healed anastomoses in nine of 12 patients with available data, including antegrade and retrograde cyclical, short single and long single patterns. Dominant frequencies in the distal colon were similar in patients and controls (2–3 cycles/min) (antegrade P = 0·482 retrograde P = 0·178). Compared with values before the meal, the mean(s.d.) number of dominant cyclical retrograde motor patterns increased in patients after the meal (2·1(2·7) versus 32·6(31·8) in 2 h respectively P & 0·001), similar to controls (P = 0·178), although the extent of propagation was 41 per cent shorter in patients, by a mean of 3·4 cm (P = 0·003). Short and long single propagating motor patterns were comparable between groups in terms of frequency, velocity, extent and litude. Motility patterns and meal responses are restored after distal colorectal resection in patients with normal bowel function. Coordinated propagation across healed anastomoses may indicate regeneration of underlying cellular networks.

Diagnosis of constipation

Publisher: Future Medicine Ltd

Date: 04-2013

DOI: 10.2217/EBO.12.337

Neuroanatomy and physiology of colorectal function and defaecation: from basic science to human clinical studies

Publisher: Wiley

Date: 12-2009

DOI: 10.1111/J.1365-2982.2009.01400.X

Abstract: Colorectal physiology is complex and involves programmed, coordinated interaction between muscular and neuronal elements. Whilst a detailed understanding remains elusive, novel information has emerged from recent basic science and human clinical studies concerning normal sensorimotor mechanisms and the organization and function of the key elements involved in the control of motility. This chapter summarizes these observations to provide a contemporary review of the neuroanatomy and physiology of colorectal function and defaecation.

Colonic manometry via appendicostomy shows reduced frequency, amplitude and length of propagating sequences in children with slow-transit constipation

Publisher: Elsevier BV

Date: 07-2005

DOI: 10.1016/J.JPEDSURG.2005.03.047

Abstract: We wish to define colonic motor function in children with slow-transit constipation (STC) using manometry catheters introduced through appendiceal stomas, previously sited for controlling fecal retention by colonic irrigation. We undertook 24-hour pancolonic manometry of 6 children (5 boys mean, 11.5 years SD, 3.0) using a multilumen silastic catheter. were compared to nasocolonic motility studies obtained in healthy young adults. Antegrade propagating sequences (APSs) originated less frequently in the cecum compared to controls. There were fewer APS (mean +/- SEM: STC, 13 +/- 6 per 24 hours controls, 52 +/- 6 per 24 hours P < .01) and high- litude propagating contractions (HAPCs: STC, 5 +/- 2 per 24 hours controls, 9.9 +/- 1.4 per 24 hours P < .05). The litude of APS and HAPC was less in STC (APS, 39 +/- 9 mm Hg controls, 54 +/- 3 per 24 hours P < .05) (HAPC: STC, 94 +/- 10 mm Hg control, 117 +/- 3 mm Hg P < .01), whereas the litude of retrograde propagating sequences was greater in STC (43 +/- 6 mm Hg control, 27 +/- 1 mm Hg P < .01). The distances propagated by HAPC were significantly less in STC (36 +/- 4.5 vs 47 +/- 2.3 cm, controls P < .05), and there was no evidence of a region-specific difference in propagation velocity of APS. Neither meal ingestion nor waking significantly increased colonic motor activity in patients with STC. Despite the small numbers available to be studied, we found that children with STC in whom an appendicostomy had been placed show significant abnormalities in pancolonic motor function.

High-Resolution Colonic Manometry Pressure Profiles Are Similar in Asymptomatic Diverticulosis and Controls

Publisher: Springer Science and Business Media LLC

Date: 12-05-2020

DOI: 10.1007/S10620-020-06320-4

Electrophysiological and morphological features of myenteric neurons of human colon revealed by intracellular recording and dye fills

Publisher: Wiley

Date: 05-02-2023

DOI: 10.1111/NMO.14538

Abstract: Ex vivo intracellular recordings and dye fills, combined with immunohistochemistry, are a powerful way to analyze the enteric nervous system of laboratory animals. Myenteric neurons were recorded in isolated specimens of human colon. A key determinant of successful recording was near‐complete removal of circular muscle from the surface of ganglia. Treatment with a collagenase/neutral protease mix before dissection significantly improved recording success and reduced damage to the plexus. Carboxyfluorescein in microelectrodes allowed recorded neurons to be routinely labeled, analyzed, and subjected to multi‐layer immunohistochemistry. Carboxyfluorescein revealed morphological details that were not detected by immunohistochemical methods. Of 54 dye‐filled myenteric neurons ( n = 22), 45 were uni‐axonal and eight were multi‐axonal. There was a significant bias toward recordings from large neural somata. The close association between morphology and electrophysiology (long after‐hyperpolarizations and fast EPSPs) seen in mice and guinea pigs did not hold for human myenteric neuron recordings. No slow EPSPs were recorded however, disruption to the myenteric plexus during dissection may have led the proportion of cells receiving synaptic potentials to be underestimated. Neurons immunoreactive for nitric oxide synthase were more excitable than non‐immunoreactive neurons. Distinctive grooves were observed on the serosal and/or mucosal faces of myenteric neurons in 3D reconstructions. These had varicose axons running through them and may represent a preferential site of synaptic inputs. Human enteric neurons share many features with laboratory animals, but the combinations of features in in idual cells appear more variable.

The use of colonic and anorectal high-resolution manometry and its place in clinical work and in research

Publisher: Wiley

Date: 30-07-2015

DOI: 10.1111/NMO.12632

Abstract: In the esophagus, high-resolution manometry (HRM) has become a standard diagnostic tool in the investigation of suspected motility disorders. However, at the opposite end of the digestive tract (i.e., the colon and anorectum), the use of HRM still remains in its infancy, with relatively few published studies in the scientific literature. Further, the clinical utility of those studies that have been performed is largely undetermined. This review assesses all of the HRM studies published to date from both the colon and anorectum, explores the catheter types used, and attempts to determine the worth of HRM over traditional 'low-resolution' recordings from the same regions. Ultimately, this review addresses whether HRM currently provides information that will benefit patient diagnosis and treatment.

Post-operative colonic manometry in children with anorectal malformations: A systematic review.

Publisher: Wiley

Date: 14-06-2022

DOI: 10.1111/NMO.14415

Abstract: Children with anorectal malformations may experience constipation and fecal incontinence following repair. The contribution of altered anorectal function to these persistent symptoms is relatively intuitive however, colonic motility in this cohort is less well understood. Manometry may be used to directly assess colonic motility. The purpose of this systematic review was to synthesize the available evidence regarding post‐operative colonic motility in children with anorectal malformations and evaluate the reported equipment and protocols used to perform colonic manometry in this cohort. This systematic review was conducted in compliance with Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA). We conducted a systematic review of four databases: Embase, MEDLINE, PubMed, and the Cochrane Library (1 st January 1985–22 nd July 2021). Studies reporting colonic manometry performed in children following anorectal malformation repair were assessed for eligibility. Data were extracted independently by two authors. Four studies were eligible for inclusion. Of the combined total cohort of 151 children, post‐operative colonic manometry was conducted in 35. Insufficient reporting of medical characteristics, bowel function, and manometric outcomes restricted comparison between studies, and limited clinical applicability. No results from high‐resolution colonic manometry were identified. Despite the prevalence of post‐operative bowel dysfunction in children with repaired anorectal malformations, this systematic review highlighted the markedly limited evidence regarding post‐operative colonic motility. This cohort may benefit from assessment with high‐resolution techniques however, future work must emphasize adherence to standardized manometry protocols, and include robust reporting of surgical characteristics, bowel function, and manometric outcomes.

Insights into the mechanisms underlying colonic motor patterns

Publisher: Wiley

Date: 09-06-2016

DOI: 10.1113/JP271919

Peristalsis and propulsion of colonic content can occur after blockade of major neuroneuronal and neuromuscular transmitters in isolated guinea pig colon

Publisher: American Physiological Society

Date: 15-12-2013

DOI: 10.1152/AJPGI.00257.2013

Abstract: We recently identified hexamethonium-resistant peristalsis in the guinea pig colon. We showed that, following acute blockade of nicotinic receptors, peristalsis recovers, leading to normal propagation velocities of fecal pellets along the colon. This raises the fundamental question: what mechanisms underlie hexamethonium-resistant peristalsis? We investigated whether blockade of the major receptors that underlie excitatory neuromuscular transmission is required for hexamethonium-resistant peristalsis. Video imaging of colonic wall movements was used to make spatiotemporal maps and determine the velocity of peristalsis. Propagation of artificial fecal pellets in the guinea pig distal colon was studied in hexamethonium, atropine, ω-conotoxin (GVIA), ibodutant (MEN-15596), and TTX. Hexamethonium and ibodutant alone did not retard peristalsis. In contrast, ω-conotoxin abolished peristalsis in some preparations and reduced the velocity of propagation in all remaining specimens. Peristalsis could still occur in some animals in the presence of hexamethonium + atropine + ibodutant + ω-conotoxin. Peristalsis never occurred in the presence of TTX. The major finding of the current study is the unexpected observation that peristalsis can occur after blockade of the major excitatory neuroneuronal and neuromuscular transmitters. Also, the colon retained an intrinsic polarity in the presence of these antagonists and was only able to expel pellets in an aboral direction. The nature of the mechanism(s)/neurotransmitter(s) that generate(s) peristalsis and facilitate(s) natural fecal pellet propulsion, after blockade of major excitatory neurotransmitters, at the neuroneuronal and neuromuscular junction remains to be identified.

Characterization of putative interneurons in the myenteric plexus of human colon

Publisher: Wiley

Date: 24-08-2021

DOI: 10.1111/NMO.13964

Potential causes of the preoperative increase in the rectosigmoid cyclic motor pattern: A high‐resolution manometry study

Publisher: Wiley

Date: 11-2021

DOI: 10.14814/PHY2.15091

Characterization of projections of longitudinal muscle motor neurons in human colon

Publisher: Wiley

Date: 29-07-2019

DOI: 10.1111/NMO.13685

Abstract: The enteric nervous system contains inhibitory and excitatory motor neurons which modulate smooth muscle contractility. Cell bodies of longitudinal muscle motor neurons have not been identified in human intestine. We used retrograde tracing ex vivo with DiI, with multiple labeling immunohistochemistry, to characterize motor neurons innervating tenial and inter-tenial longitudinal muscle of human colon. The most abundant immunohistochemical markers in the tertiary plexus were vesicular acetylcholine transporter, nitric oxide synthase (NOS), and vasoactive intestinal polypeptide (VIP). Of retrogradely traced motor neurons innervating inter-tenial longitudinal muscle, 95% were located within 6mm oral or anal to the DiI application site. Excitatory motor neuron cell bodies, immunoreactive for choline acetyltransferase (ChAT), were clustered aborally, whereas NOS-immunoreactive cell bodies were distributed either side of the DiI application site. Motor neurons had small cell bodies, averaging 438 + 18µm Tenial and inter-tenial motor neurons innervating the longitudinal muscle have short projections. Inhibitory motor neurons have less polarized projections than cholinergic excitatory motor neurons. Longitudinal and circular muscle layers are innervated by distinct local populations of excitatory and inhibitory motor neurons. A population of human enteric neurons that contribute significantly to colonic motility has been characterized.

Optimal stomatal behaviour around the world

Publisher: Springer Science and Business Media LLC

Date: 02-03-2015

DOI: 10.1038/NCLIMATE2550

In-vivo demonstration of a high resolution optical fiber manometry catheter for diagnosis of gastrointestinal motility disorders

Publisher: The Optical Society

Date: 05-03-2009

DOI: 10.1364/OE.17.004500

Abstract: Fiber optic catheters for the diagnosis of gastrointestinal motility disorders are demonstrated in-vitro and in-vivo. Single element catheters have been verified against existing solid state catheters and a multi-element catheter has been demonstrated for localized and full esophageal monitoring. The multi-element catheter consists of a series of closely spaced pressure sensors that pick up the peristaltic wave traveling along the gastrointestinal (GI) tract. The sensors are spaced on a 10 mm pitch allowing a full interpolated image of intraluminal pressure to be generated. Details are given of in-vivo trials of a 32-element catheter in the human oesophagus and the suitability of similar catheters for clinical evaluation in other regions of the human digestive tract is discussed. The fiber optic catheter is significantly smaller and more flexible than similar commercially available devices making intubation easier and improving patient tolerance during diagnostic procedures.

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

Publisher: Wiley

Date: 29-01-2013

DOI: 10.1111/NMO.12077

Abstract: 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. 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 in idual data set were randomized (expected) and reanalyzed. 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 in idual patients falling outside of the range of indicator values for controls. 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.

Motor patterns in the proximal and distal mouse colon which underlie formation and propulsion of feces

Publisher: Wiley

Date: 15-02-2021

DOI: 10.1111/NMO.14098

Abstract: In herbivores, the proximal and distal colonic regions feature distinct motor patterns underlying formation and propulsion of fecal pellets, respectively. Omnivores, such as mice and humans, lack a similar clear anatomical transition between colonic regions. We investigated whether distinct processes form and propel content along the large intestine of a mouse (an omnivore). We recorded propulsive and non‐propulsive neurogenic motor activity in mouse large intestine under six different stimulus conditions of varying viscosities. Gut wall movements were recorded by video and smooth muscle electrical behavior recorded with extracellular suction electrodes. Three major neurally mediated motor patterns contributed to pellet formation and propulsion. (1) Pellet‐shaped boluses are pinched off near the ceco‐colonic junction and slowly propelled distally to a transition located at 40% length along the colon. (2) At this functional colonic flexure, propulsion speed is significantly increased by self‐sustaining neural peristalsis. Speed transition at this location also occurs with artificial pellets and with spontaneously formed boluses in the empty colon. (3) Periodic colonic motor complexes (CMCs) were present in all conditions reaching a maximal frequency of about 0.4 cpm and extending across the proximal and distal colon with faster speed of propagation. The three motor patterns share a unique underlying fundamental property of the enteric circuits, which involve extended ensembles of enteric neurons firing at close to 2 Hz. The demonstration of distinct functional differences between proximal and distal colon in rabbit, guinea pig, and now mouse raises the possibility that this may be an organizational principle in other mammalian species, including humans.

Inhibited postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome

Publisher: American Physiological Society

Date: 07-2023

DOI: 10.1152/AJPGI.00114.2022

Abstract: Compared with healthy adults this study has shown a significant reduction in the prevalence of the postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome. We hypothesize that this altered motility may allow for premature rectal filling which contributes to the postprandial urgency and diarrhea experienced by these patients.

Colonic Manometry: What Do the Squiggly Lines Really Tell Us?

Publisher: Springer Netherlands

Date: 2013

DOI: 10.1007/978-94-007-6561-0_11

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

Publisher: Wiley

Date: 05-2008

DOI: 10.1111/J.1365-2982.2007.01060.X

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 (99m)Tc 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 litude PSs, with component pressure waves between 2 mmHg and 5 mmHg, were as likely to be associated with colonic movements as higher litude PSs. As such there was no correlation between the litude 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.

Analysis of Intestinal Movements with Spatiotemporal Maps: Beyond Anatomy and Physiology

Publisher: Springer International Publishing

Date: 2022

DOI: 10.1007/978-3-031-05843-1_26

Identifying Types of Neurons in the Human Colonic Enteric Nervous System

Publisher: Springer International Publishing

Date: 2022

DOI: 10.1007/978-3-031-05843-1_23

Predicting the activation states of the muscles governing upper esophageal sphincter relaxation and opening

Publisher: American Physiological Society

Date: 15-03-2016

DOI: 10.1152/AJPGI.00388.2015

Abstract: The swallowing muscles that influence upper esophageal sphincter (UES) opening are centrally controlled and modulated by sensory information. Activation and deactivation of neural inputs to these muscles, including the intrinsic cricopharyngeus (CP) and extrinsic submental (SM) muscles, results in their mechanical activation or deactivation, which changes the diameter of the lumen, alters the intraluminal pressure, and ultimately reduces or promotes flow of content. By measuring the changes in diameter, using intraluminal impedance, and the concurrent changes in intraluminal pressure, it is possible to determine when the muscles are passively or actively relaxing or contracting. From these “mechanical states” of the muscle, the neural inputs driving the specific motor behaviors of the UES can be inferred. In this study we compared predictions of UES mechanical states directly with the activity measured by electromyography (EMG). In eight subjects, pharyngeal pressure and impedance were recorded in parallel with CP- and SM-EMG activity. UES pressure and impedance swallow profiles correlated with the CP-EMG and SM-EMG recordings, respectively. Eight UES muscle states were determined by using the gradient of pressure and impedance with respect to time. Guided by the level and gradient change of EMG activity, mechanical states successfully predicted the activity of the CP muscle and SM muscle independently. Mechanical state predictions revealed patterns consistent with the known neural inputs activating the different muscles during swallowing. Derivation of “activation state” maps may allow better physiological and pathophysiological interpretations of UES function.

Assessment of intraluminal impedance for the detection of pharyngeal bolus flow during swallowing in healthy adults

Publisher: American Physiological Society

Date: 2006

DOI: 10.1152/AJPGI.00011.2005

Abstract: Intraluminal impedance, a nonradiological method for assessing bolus flow within the gut, may be suitable for investigating pharyngeal disorders. This study evaluated an impedance technique for the detection of pharyngeal bolus flow during swallowing. Patterns of pharyngoesophageal pressure and impedance were simultaneously recorded with videofluoroscopy in 10 healthy volunteers during swallowing of liquid, semisolid, and solid boluses. The timing of bolus head and tail passage recorded by fluoroscopy was correlated with the timing of impedance drop and recovery at each recording site. Bolus swallowing produced a drop in impedance from baseline followed by a recovery to at least 50% of baseline. The timing of the pharyngeal and esophageal impedance drop correlated with the timing of the arrival of the bolus head. In the pharynx, the timing of impedance recovery was delayed relative to the timing of clearance of the bolus tail. In contrast, in the upper esophageal sphincter (UES) and proximal esophagus, the timing of impedance recovery correlated well with the timing of clearance of the bolus tail. Impedance-based estimates of pharyngoesophageal bolus clearance time correlated with true pharyngoesophageal bolus clearance time. Patterns of intraluminal impedance recorded in the pharynx during bolus swallowing are therefore more complex than those in the esophagus. During swallowing, mucosal contact between the tongue base and posterior pharyngeal wall prolongs the duration of pharyngeal impedance drop, leading to overestimation of bolus tail timing. Therefore, we conclude that intraluminal impedance measurement does not accurately reflect the bolus transit in the pharynx but does accurately reflect bolus transit across the UES and below.

Validation of a semi-automated scintigraphic technique for detecting episodic, real-time colonic flow

Publisher: Wiley

Date: 07-2006

DOI: 10.1111/J.1365-2982.2006.00796.X

Abstract: The relationships between the movement of colonic content and regional pressures have only been partially defined. During the analysis of a combined colonic scintigraphic and manometric study, a quantitative technique for determining discrete, episodic, real-time colonic flow was developed. Our aim was to validate this technique through the construction of a computer-generated phantom model of known antegrade and retrograde motility. The anthropoid phantom was rasterized into a 6-mm voxel model to create a 3D voxel phantom of the colon with four distinct colonic segments. Associating a time/activity curve with each segment simulated dynamic behaviour. Activity in the model was based on data obtained from human colonic scintigraphic recordings using 30 MBq of (99m)Tc sulphur colloid. The flow was simulated by modifying the input time/activity functions to represent episodes of net flow of 2%, 5% or 10% of segmental content. Our quantitative technique was applied to the phantom model to measure the accuracy with which simulated flows were detected. Our quantitative technique proved to be a sensitive and specific means of detecting the presence and the magnitude of discrete episodes of colonic flow and therefore, should improve our ability to correlate colonic flow and motor patterns.

Novel diagnostics and therapy of colonic motor disorders

Publisher: Elsevier BV

Date: 12-2011

DOI: 10.1016/J.COPH.2011.10.002

Abstract: Colonic motor abnormalities are implicated in several gastrointestinal disorders including constipation, irritable bowel syndrome and functional diarrhoea. Defining the colonic abnormalities is difficult and several novel techniques including, high-resolution fibre optic manometry, wireless motility capsules, ultrasound and magnetic resonance imaging have emerged to help in the diagnosis of these conditions. Coupled with the developing techniques are the novel treatments that look to restore normal colonic motility. These treatments include pharmacological agents (pharmabiotics, serotonin agonist, secretagogues) and medical devices (sacral nerve stimulation, transcutaneous electrical stimulation and biofeedback). This review summarizes the novel techniques used to record and define colonic motor abnormalities and the current status of the emerging treatments used to treat them.

Treatment efficacy of sacral nerve stimulation in slow transit constipation: A two-phase, double-blind randomized controlled crossover study

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 05-2015

DOI: 10.1038/AJG.2015.101

Abstract: Sacral nerve stimulation (SNS) is a potential treatment for constipation refractory to standard therapies. However, there have been no randomized controlled studies examining its efficacy. In patients with slow transit constipation, we evaluated the efficacy of suprasensory and subsensory SNS compared with sham, in a prospective, 18-week randomized, double-blind, placebo-controlled, two-phase crossover study. The primary outcome measure was the proportion of patients who, on more than 2 days/week for at least 2 of 3 weeks, reported a bowel movement associated with a feeling of complete evacuation. After 3 weeks of temporary peripheral nerve evaluation (PNE), all patients had permanent implantation and were randomized to subsensory/sham (3 weeks each) and then re-randomized to suprasensory/sham (3 weeks each) with a 2-week washout period between each arm. Daily stool dairies were kept, and quality of life (QoL SF36) was measured at the end of each arm. Between November 2006 and March 2012, 234 constipated patients were assessed, of whom 59 were willing and deemed eligible to participate (4 male median age 42 years). Of the 59 patients, 16 (28%) responded to PNE. Fifty-five patients went on to permanent SNS implantation. The proportion of patients satisfying the primary outcome measure did not differ between suprasensory (30%) and sham (21%) stimulations, nor between subsensory (25%) and sham (25%) stimulations. There were no significant changes in QoL scores. In patients with refractory slow transit constipation, SNS did not improve the frequency of complete bowel movements over the 3-week active period.

Community-Derived Indicator Domains for Social Resilience to Water Quality Decline in a Great Barrier Reef Catchment, Australia

Publisher: Informa UK Limited

Date: 05-2012

DOI: 10.1080/08941920.2011.608183

Neurally mediated propagating discrete clustered contractions superimposed on myogenic ripples in ex vivo segments of human ileum

Publisher: American Physiological Society

Date: 2015

DOI: 10.1152/AJPGI.00230.2014

Abstract: Narrow muscle strips have been extensively used to study intestinal contractility. Larger specimens from laboratory animals have provided detailed understanding of mechanisms that underlie patterned intestinal motility. Despite progress in animal tissue, investigations of motor patterns in large, intact specimens of human gut ex vivo have been sparse. In this study, we tested whether neurally dependent motor patterns could be detected in isolated specimens of intact human ileum. Specimens ( n = 14 7–30 cm long) of terminal ileum were obtained with prior informed consent from patients undergoing colonic surgery for removal of carcinomas. Preparations were set up in an organ bath with an array of force transducers, a fiberoptic manometry catheter, and a video camera. Spontaneous and distension-evoked motor activity was recorded, and the effects of lidocaine, which inhibits neural activity, were studied. Myogenic contractions (ripples) occurred in all preparations (6.17 ± 0.36/min). They were of low litude and formed complex patterns by colliding and propagating in both directions along the specimen at anterograde velocities of 4.1 ± 0.3 mm/s and retrogradely at 4.9 ± 0.6 mm/s. In five specimens, larger litude clusters of contractions were seen (discrete clustered contractions), which propagated aborally at 1.05 ± 0.13 mm/s and orally at 1.07 ± 0.09 mm/s. These consisted of two to eight phasic contractions that aligned with ripples. These motor patterns were abolished by addition of lidocaine (0.3 mM). The ripples continued unchanged in the presence of this neural blocking agent. These results demonstrate that both myogenic and neurogenic motor patterns can be studied in isolated specimens of human small intestine.

Manometric demonstration of duodenal/jejunal motor function consistent with the duodenal brake mechanism

Publisher: Wiley

Date: 13-03-2020

DOI: 10.1111/NMO.13835

The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function

Publisher: Wiley

Date: 12-08-2019

DOI: 10.1111/NMO.13679

Role of descending inhibition in transport of fluid contents in the colon

Publisher: Springer Berlin Heidelberg

Date: 2010

DOI: 10.1007/978-3-642-14515-5_257

Colonic motor abnormalities in slow transit constipation defined by high resolution, fibre-optic manometry.

Publisher: Wiley

Date: 03-01-2015

DOI: 10.1111/NMO.12502

Abstract: Slow transit constipation (STC) is associated with colonic motor abnormalities. The underlying cause(s) of the abnormalities remain poorly defined. In health, utilizing high resolution fiber-optic manometry, we have described a distal colonic propagating motor pattern with a slow wave frequency of 2-6 cycles per minute (cpm). A high calorie meal caused a rapid and significant increase in this activity, suggesting the intrinsic slow wave activity could be mediated by extrinsic neural input. Utilizing the same protocol our aim was to characterize colonic meal response STC patients. A fiber-optic manometry catheter (72 sensors at 1 cm intervals) was colonoscopically placed with the tip clipped at the ascending or transverse colon, in 14 patients with scintigraphically confirmed STC. Manometric recordings were taken, for 2 h pre and post a 700 kCal meal. Data were compared to 12 healthy adults. Prior to and/or after the meal the cyclic propagating motor pattern was identified in 13 of 14 patients. However, the meal, did not increase the cyclic motor pattern (preprandial 7.4 ± 7.6 vs postprandial 8.3 ± 4.5 per/2 h), this is in contrast to the dramatic increase observed in health (8.3 ± 13.3 vs 59.1 ± 89.0 per/2 h p < 0.001). In patients with STC a meal fails to induce the normal increase in the distal colonic cyclic propagating motor patterns. We propose that these data may indicate that the normal extrinsic parasympathetic inputs to the colon are attenuated in these patients.

Neurogenic and myogenic motor activity in the colon of the guinea pig, mouse, rabbit, and rat

Publisher: American Physiological Society

Date: 15-11-2013

DOI: 10.1152/AJPGI.00227.2013

Abstract: Gastrointestinal motility involves interactions between myogenic and neurogenic processes intrinsic to the gut wall. We have compared the presence of propagating myogenic contractions of the isolated colon in four experimental animals (guinea pig, mouse, rabbit, and rat), following blockade of enteric neural activity. Isolated colonic preparations were distended with fluid, with the anal end either closed or open. Spatiotemporal maps of changes in diameter were constructed from video recordings. Distension-induced peristaltic contractions were abolished by tetrodotoxin (TTX 0.6 μM) in all animal species. Subsequent addition of carbachol (0.1–1 μM) did not evoke myogenic motor patterns in the mouse or guinea pig, although some activity was observed in rabbit and rat colon. These myogenic contractions propagated both orally and anally and differed from neurogenic propagating contractions in their frequency, extent of propagation, and polarity. Niflumic acid (300 μM), used to block myogenic activity, also blocked neural peristalsis and thus cannot be used to discriminate between these mechanisms. In all species, except the mouse colon, small myogenic “ripple” contractions were revealed in TTX, but in both rat and rabbit an additional, higher-frequency ripple-type contraction was superimposed. Following blockade of enteric nerve function, a muscarinic agonist can evoke propulsive myogenic peristaltic contractions in isolated rabbit and rat colon, but not in guinea pig or mouse colon. Marked differences between species exist in the ability of myogenic mechanisms to propel luminal content, but in all species there is normally a complex interplay between neurogenic and myogenic processes.

Optimal criteria for detecting bolus passage across the pharyngo-oesophageal segment during the normal swallow using intraluminal impedance recording

Publisher: Wiley

Date: 05-2008

DOI: 10.1111/J.1365-2982.2007.01053.X

Abstract: The impedance criteria for the detection of the arrival of bolus head and clearance of bolus tail in the pharynx have not been defined, and may differ from accepted criteria used in the oesophagus. Our aim was to define the optimal impedance criteria that most accurately defined passage of the swallowed bolus moving through the pharyngo-oesophageal segment. In eight healthy volunteers, an assembly incorporating seven impedance-measuring segments was positioned across the pharyngo-oesophageal segment, and subjects swallowed liquid and semisolid radio-opaque boluses (2-20 mL) while impedance was simultaneously recorded with videofluoroscopic images. To derive the optimal criteria, in an iterative process we correlated impedance defined bolus presence with fluoroscopy (Cohen's Kappa) for a range of impedance cut-off values from 100% to 0% for both the initial fall, and recovery of impedance. Bolus presence in the pharynx, as determined by the 'standard' criteria (50% drop and recovery to 50% of baseline), correlated very modestly with videofluoroscopy (kappa approximately 0.35). The criteria that most accurately defined bolus passage varied between pharyngeal regions. Threshold (% of baseline) for bolus head entry into the region ranged from 71% to 80%. Threshold for bolus tail clearance varied from nadir to 19%. Correlation of impedance with videofluoroscopy improved to kappa approximately 0.6 with the above criteria. The impedance criteria defining bolus presence across the pharyngo-oesophageal segment differ from those adopted in the oesophagus. Pharyngeal impedance provides an accurate, non-radiological indicator of bolus transit through the pharynx.

Neural mechanisms of peristalsis in the isolated rabbit distal colon: A neuromechanical loop hypothesis

Publisher: Frontiers Media SA

Date: 16-04-2014

DOI: 10.3389/FNINS.2014.00075

The use of wavelength division multiplexed fiber bragg grating sensors for distributed sensing of pressure in the gastrointestinal tract

Publisher: IEEE

Date: 12-2008

DOI: 10.1109/IPGC.2008.4781397

A fibre optic catheter for simultaneous measurement of longitudinal and circumferential muscular activity in the gastrointestinal tract

Publisher: Wiley

Date: 28-03-2011

DOI: 10.1002/JBIO.201000056

Abstract: Diagnostic catheters based on fibre Bragg gratings (FBG's) are proving to be highly effective for measurement of the muscular activity associated with motility in the human gut. While the primary muscular contractions that generate peristalsis are circumferential in nature, it has long been known that there is also a component of longitudinal contractility present, acting in harmony with the circumferential component to improve the overall efficiency of material movement. We report the detection of longitudinal motion in mammalian intestine using an FBG technique that should be viable for similar detection in humans. The longitudinal sensors have been combined with our previously reported FBG pressure sensing elements to form a composite catheter that allows the relative phase between the two components to be detected. The catheter output has been validated using video mapping in an ex-vivo rabbit ileum preparation.

The impact of laxative use upon symptoms in patients with proven slow transit constipation

Publisher: Springer Science and Business Media LLC

Date: 10-11-2011

DOI: 10.1186/1471-230X-11-121

Duodenal and proximal jejunal motility inhibition associated with bisacodyl induced colonic high amplitude propagating contractions

Publisher: American Physiological Society

Date: 09-2021

DOI: 10.1152/AJPGI.00209.2021

Abstract: The present study has shown, for the first time, that the presence of high- litude propagating contractions induced by bisacodyl is associated with a significant reduction in small bowel motility. These findings support of possible existence of a reflex pathway that causes inhibition of small bowel motility in response to rectal distension.

Is serotonin in enteric nerves required for distension-evoked peristalsis and propulsion of content in guinea-pig distal colon?

Publisher: Elsevier BV

Date: 06-2013

DOI: 10.1016/J.NEUROSCIENCE.2013.02.061

Abstract: Recent studies have shown genetic deletion of the gene that synthesizes 5-HT in enteric neurons (tryptophan hydroxylase-2, Tph-2) leads to a reduction in intestinal transit. However, deletion of the Tph-2 gene also leads to major developmental changes in enteric ganglia, which could also explain changes in intestinal transit. We sought to investigate this further by acutely depleting serotonin from enteric neurons over a 24-h period, without the confounding influences induced by genetic manipulation. Guinea-pigs were injected with reserpine 24h prior to euthanasia. Video-imaging and spatio-temporal mapping was used to record peristalsis evoked by natural fecal pellets, or slow infusion of intraluminal fluid. Immunohistochemical staining for 5-HT was used to detect the presence of serotonin in the myenteric plexus. It was found that endogenous 5-HT was always detected in myenteric ganglia of control animals, but never in guinea-pigs treated with reserpine. Interestingly, peristalsis was still reliably evoked by either intraluminal fluid, or fecal pellets in reserpine-treated animals that also had their entire mucosa and submucosal plexus removed. In these 5-HT depleted animals, there was no change in the frequency of peristalsis or force generated during peristalsis. In control animals, or reserpine treated animals, high concentrations (up to 10 μM) of ondansetron and SDZ-205-557, or granisetron and SDZ-205-557 had no effect on peristalsis. In summary, acute depletion of serotonin from enteric nerves does not prevent distension-evoked peristalsis, nor propulsion of luminal content. Also, we found no evidence that 5-HT3 and 5-HT4 receptor activation is required for peristalsis, or propulsion of contents to occur. Taken together, we suggest that the intrinsic mechanisms that generate peristalsis and entrain propagation along the isolated guinea-pig distal colon are independent of 5-HT in enteric neurons or the mucosa, and do not require the activation of 5-HT3 or 5-HT4 receptors.

Luminal Chemoreceptors and Intrinsic Nerves: Key Modulators of Digestive Motor Function

Publisher: Springer International Publishing

Date: 2022

DOI: 10.1007/978-3-031-05843-1_3

A new understanding of the physiology and pathophysiology of colonic motility?

Publisher: Wiley

Date: 04-07-2018

DOI: 10.1111/NMO.13395

Abstract: In recent years, high-resolution manometry has been used in an attempt to gain a greater insight into the physiology athophysiology of colonic contractile activity in healthy adults and patients with colonic motility disorders. New colonic motor patterns have been identified and characterized, however, the clinical significance of these findings remains undetermined. This review will assess the current literature on colonic high-resolution manometry and determine if this procedure has advanced our understanding of colonic motility. The limitations, future directions, and the potential of this technique to assess the effects of treatment upon colonic motor patterns will also be discussed.

5-HT3 and 5-HT4 antagonists inhibit peristaltic contractions in guinea-pig distal colon by mechanisms independent of endogenous 5-HT

Publisher: Frontiers Media SA

Date: 2013

DOI: 10.3389/FNINS.2013.00136

Determinants of postprandial flow across the human ileocaecal junction: a combined manometric and scintigraphic study

Publisher: Wiley

Date: 10-2008

DOI: 10.1111/J.1365-2982.2008.01145.X

Abstract: The relationships between ileocolonic motor patterns and flow have not been defined in humans. Utilizing simultaneous ileocolonic manometry and scintiscanning, we aimed to examine this relationship and test the hypotheses that ileal propagating sequences (PSs) underlie caecal filling, that caecal filling is a stimulus for proximal colonic PSs and that the ileocolonic junction (ICJ) regulates flow between the small and large bowel. In six healthy volunteers, a 5-m-long nasocolonic manometry catheter was positioned such that 16 recording sites, spaced at 7.5-cm intervals, spanned the ileum and proximal colon. Subjects were positioned under a gamma camera 30 MBq of (99m)Tc sulphur colloid was instilled, 22.5 cm proximal to the ICJ. Isotopic images were recorded (10 s per frame) and synchronized with the manometric trace. We identified 171 ileal PSs, 47 caecal PSs and 117 discrete episodes of caecal filling. Of the 117 episodes of caecal filling, 72% were associated temporally with ileal PSs. Conversely, 87% of ileal PSs were associated with caecal filling. Of the PSs originating in the caecum, 90% were temporally associated with caecal filling. We conclude that ileal PSs are highly propulsive and are the major determinant of episodic caecal filling and that caecal filling may be a major stimulus for caecal propagating sequences.

Impact of exercise duration on gastrointestinal function and symptoms

Publisher: American Physiological Society

Date: 2023

DOI: 10.1152/JAPPLPHYSIOL.00393.2022

Abstract: Exercise stress per se appears to instigate perturbations to gastric myoelectrical activity, resulting in an increase in bradygastria frequency, inferring a reduction in gastric motility. The perturbations to gastrointestinal functional responses instigated by exercise per se, likely contribute to the high incidence and severity level of exercise-associated gastrointestinal symptoms. Cutaneous electrogastrography is not commonly used in exercise gastroenterology research, however, may be a useful aid in providing an overall depiction of gastrointestinal function. Particularly relating to gastrointestinal motility and concerning gastroparesis.

Colonic Response to Physiological, Chemical, Electrical and Mechanical Stimuli; What Can Be Used to Define Normal Motility?

Publisher: Springer International Publishing

Date: 2022

DOI: 10.1007/978-3-031-05843-1_12

An experimental method to identify neurogenic and myogenic active mechanical states of intestinal motility

Publisher: Frontiers Media SA

Date: 2013

DOI: 10.3389/FNSYS.2013.00007

Surgical management of constipation

Publisher: Wiley

Date: 12-2009

DOI: 10.1111/J.1365-2982.2009.01405.X

Abstract: This review addresses the range of operations suggested to be of contemporary value in the treatment of constipation with critical evaluation of efficacy data, complications, patient selection, controversies and areas for future research.

Artisanal fish fences pose broad and unexpected threats to the tropical coastal seascape

Publisher: Springer Science and Business Media LLC

Date: 21-05-2019

DOI: 10.1038/S41467-019-10051-0

Abstract: Gear restrictions are an important management tool in small-scale tropical fisheries, improving sustainability and building resilience to climate change. Yet to identify the management challenges and complete footprint of in idual gears, a broader systems approach is required that integrates ecological, economic and social sciences. Here we apply this approach to artisanal fish fences, intensively used across three oceans, to identify a previously underrecognized gear requiring urgent management attention. A longitudinal case study shows increased effort matched with large declines in catch success and corresponding reef fish abundance. We find fish fences to disrupt vital ecological connectivity, exploit 500 species with high juvenile removal, and directly damage seagrass ecosystems with cascading impacts on connected coral reefs and mangroves. As semi-permanent structures in otherwise open-access fisheries, they create social conflict by assuming unofficial and unregulated property rights, while their unique high-investment-low-effort nature removes traditional economic and social barriers to overfishing.

Grazing and ecosystem service delivery in global drylands

Publisher: American Association for the Advancement of Science (AAAS)

Date: 25-11-2022

DOI: 10.1126/SCIENCE.ABQ4062

Abstract: Grazing represents the most extensive use of land worldwide. Yet its impacts on ecosystem services remain uncertain because pervasive interactions between grazing pressure, climate, soil properties, and bio ersity may occur but have never been addressed simultaneously. Using a standardized survey at 98 sites across six continents, we show that interactions between grazing pressure, climate, soil, and bio ersity are critical to explain the delivery of fundamental ecosystem services across drylands worldwide. Increasing grazing pressure reduced ecosystem service delivery in warmer and species-poor drylands, whereas positive effects of grazing were observed in colder and species-rich areas. Considering interactions between grazing and local abiotic and biotic factors is key for understanding the fate of dryland ecosystems under climate change and increasing human pressure.

Activation of intestinal spinal afferent endings by changes in intra-mesenteric arterial pressure.

Publisher: Wiley

Date: 25-06-2015

DOI: 10.1113/JP270378

Interpreting manometric signals for propulsion in the gut

Publisher: Springer Science and Business Media LLC

Date: 23-06-2015

DOI: 10.1007/S40571-015-0050-Y

Automated Analysis Using a Bayesian Functional Mixed-Effects Model With Gaussian Process Responses for Wavelet Spectra of Spatiotemporal Colonic Manometry Signals

Publisher: Frontiers Media SA

Date: 11-02-2021

DOI: 10.3389/FPHYS.2020.605066

Abstract: Manual analysis of human high-resolution colonic manometry data is time consuming, non-standardized and subject to laboratory bias. In this article we present a technique for spectral analysis and statistical inference of quasiperiodic spatiotemporal signals recorded during colonic manometry procedures. Spectral analysis is achieved by computing the continuous wavelet transform and cross-wavelet transform of these signals. Statistical inference is achieved by modeling the resulting time-averaged litudes in the frequency and frequency-phase domains as Gaussian processes over a regular grid, under the influence of categorical and numerical predictors specified by the experimental design as a functional mixed-effects model. Parameters of the model are inferred with Hamiltonian Monte Carlo. Using this method, we re-analyzed our previously published colonic manometry data, comparing healthy controls and patients with slow transit constipation. The output from our automated method, supports and adds to our previous manual analysis. To obtain these results took less than two days. In comparison the manual analysis took 5 weeks. The proposed mixed-effects model approach described here can also be used to gain an appreciation of cyclical activity in in idual subjects during control periods and in response to any form of intervention.

pathophysiology of colonic causes of chronic constipation

Publisher: Wiley

Date: 12-10-2009

DOI: 10.1111/J.1365-2982.2009.01401.X

The relationships between the results of contemporary tests of anorectal structure and sensorimotor function and the severity of fecal incontinence

Publisher: Wiley

Date: 19-07-2020

DOI: 10.1111/NMO.13946

Development and feasibility of an ambulatory acquisition system for fiber‐optic high‐resolution colonic manometry

Publisher: Wiley

Date: 13-08-2019

DOI: 10.1111/NMO.13704

Abstract: High-resolution colonic manometry is an emerging technique that has provided new insights into the pathophysiology of functional colorectal diseases. Prior studies have been limited by bulky, non-ambulatory acquisition systems, which have prevented mobilization during prolonged recordings. A novel ambulatory acquisition system for fiber-optic high-resolution colonic manometry was developed. Benchtop validation against a standard non-ambulatory system was performed using standardized calibration metrics. Clinical feasibility studies were conducted in three patients undergoing right hemicolectomy. Pressure profiles obtained from benchtop testing were near-identical using the ambulatory and the non-ambulatory systems. Clinical studies successfully demonstrated ambulatory data capture with patients freely mobilizing postoperatively during continuous recordings of >60 hours. The occurrence (P = .56), litude (P = .65), velocity (P = .10), and extent (P = .12) of colonic motor patterns were similar to those obtained in non-ambulatory studies. A novel ambulatory system for high-resolution colonic manometry has been developed and validated. This technique will facilitate prolonged ambulatory recordings of colonic motor activity, assisting with investigations into the role of colonic motility in disease states.

The human enteric nervous system. Historical and modern advances. Collaboration between science and surgery

Publisher: Wiley

Date: 11-04-2022

DOI: 10.1111/ANS.17688

Abstract: There are considerable advantages and opportunities for surgeons and trainee surgeons in conducting a period of research allied with basic scientists. Such clinicians are well placed to define relevant clinical questions, provide human material (tissue, biopsy and blood) and translate the techniques derived in experimental animals to human subjects. This small review explores research conducted on the nervous system of the intestines, with an emphasis on the translation of findings from animal to human. This work shows that new techniques of immunohistochemistry and retrograde tracing, developed in animal tissue, have greatly expanded our knowledge of the structure of the human enteric nervous system. Such findings have sparked therapeutic trials for the treatment of gastrointestinal disorders in patients.

Author's reply: The effect of sacral nerve stimulation on distal colonic motility in patients with faecal incontinence (Br J Surg 2013; 100: 959–968)

Publisher: Oxford University Press (OUP)

Date: 12-08-2013

DOI: 10.1002/BJS.9245

Postoperative ileus: mechanisms and future directions for research

Publisher: Wiley

Date: 23-04-2014

DOI: 10.1111/1440-1681.12220

Abstract: Postoperative ileus (POI) is an abnormal pattern of gastrointestinal motility characterized by nausea, vomiting, abdominal distension and/or delayed passage of flatus or stool, which may occur following surgery. Postoperative ileus slows recovery, increases the risk of developing postoperative complications and confers a significant financial load on healthcare institutions. The aim of the present review is to provide a succinct overview of the clinical features and pathophysiological mechanisms of POI, with final comment on selected directions for future research.Terminology used when describing POI is inconsistent, with little differentiation made between the obligatory period of gut dysfunction seen after surgery ('normal POI') and the more clinically and pathologically significant entity of a 'prolonged POI'. Both normal and prolonged POI represent a fundamentally similar pathophysiological phenomenon. The aetiology of POI is postulated to be multifactorial, with principal mediators being inflammatory cell activation, autonomic dysfunction (both primarily and as part of the surgical stress response), agonism at gut opioid receptors, modulation of gastrointestinal hormone activity and electrolyte derangements. A final common pathway for these effectors is impaired contractility and motility and gut wall oedema. There are many potential directions for future research. In particular, there remains scope to accurately characterize the gastrointestinal dysfunction that underscores an ileus, development of an accurate risk stratification tool will facilitate early implementation of preventive measures and clinical appraisal of novel therapeutic strategies that target in idual pathways in the pathogenesis of ileus warrant further investigation.

Discriminating movements of liquid and gas in the rabbit colon with impedance manometry

Publisher: Wiley

Date: 13-12-2018

DOI: 10.1111/NMO.13263

Abstract: High-resolution impedance manometry is a technique that is well established in esophageal motility studies for relating motor patterns to bolus flow. The use of this technique in the colon has not been established. In isolated segments of rabbit proximal colon, we recorded motor patterns and the movement of liquid or gas boluses with a high-resolution impedance manometry catheter. These detected movements were compared to video recorded changes in gut diameter. Using the characteristic shapes of the admittance (inverse of impedance) and pressure signals associated with gas or liquid flow we developed a computational algorithm for the automated detection of these events. Propagating contractions detected by video were also recorded by manometry and impedance. Neither pressure nor admittance signals alone could distinguish between liquid and gas transit, however the precise relationship between admittance and pressure signals during bolus flow could. Training our computational algorithm upon these characteristic shapes yielded a detection accuracy of 87.7% when compared to gas or liquid bolus events detected by manual analysis. Characterizing the relationship between both admittance and pressure recorded with high-resolution impedance manometry can not only help in detecting luminal transit in real time, but also distinguishes between liquid and gaseous content. This technique holds promise for determining the propulsive nature of human colonic motor patterns.

High Resolution Colonic Manometry – What Have We Learnt?- a Review of the Literature 2012

Publisher: Springer Science and Business Media LLC

Date: 25-05-2013

DOI: 10.1007/S11894-013-0328-2

Abstract: Despite its size and physiological importance, the human colon is one of the least understood organs of the body. Many disorders arise from suspected abnormalities in colonic contractions, yet, due largely to technical constraints, investigation of human colonic motor function still remains relatively primitive. Most measures of colonic motility focus upon the transit speed (radiology, scintigraphy and, more recently, "smart pills") however, only colonic manometry can measure pressure/force from multiple regions within the colon in real time (Dinning and Scott (Curr Opin Pharmacol 11:624-629, 2011)). Based upon data from colonic manometry studies, a number of different colonic motor patterns have been distinguished: (1) antegrade high litude propagating sequences (contractions), (2) low litude propagating sequences, (3) non-propagating contractions, and (4) and rarely episodes of retrograde (oral) propagating pressure waves (Dining and Di Lorenzo (Best Pract Res Clin Gastrolenterol 25(1): 89-101, 2011)). Abnormalities in the characteristics of these motor patterns should help to characterize dysmotility in a patient populations, and in both adults and children colonic motor abnormalities have been identified with manometry studies (Rao et al. Am J Gastroenterol 99(12):2405-2416, (2004), Di Lorenzo et al. Gut. 34(1): 803-807, (1993)). Yet, despite more than two decades of such studies, the clinical utility of colonic manometry remains marginal with no specific manometric biomarkers of colonic dysfunction being established ([Camilleri et al. Neurogastroenterol Motil. 20(12): 1269-1282, 2008). This has been highlighted recently in a colonic manometry study by Singh et al. (2013), in which 41 % of 80 patients, with confirmed slow transit constipation, were reported to have normal motility. While this may suggest that no motor abnormalities exist in a proportion of such patients, the finding may also reflect technical constraints in our ability to detail colonic motility patterns.

The effect of luminal content and rate of occlusion on the interpretation of colonic manometry

Publisher: Wiley

Date: 10-12-2013

DOI: 10.1111/NMO.12051

Long range synchronization within the enteric nervous system underlies propulsion along the large intestine in mice

Publisher: Springer Science and Business Media LLC

Date: 10-08-2021

DOI: 10.1038/S42003-021-02485-4

Abstract: How the Enteric Nervous System (ENS) coordinates propulsion of content along the gastrointestinal (GI)-tract has been a major unresolved issue. We reveal a mechanism that explains how ENS activity underlies propulsion of content along the colon. We used a recently developed high-resolution video imaging approach with concurrent electrophysiological recordings from smooth muscle, during fluid propulsion. Recordings showed pulsatile firing of excitatory and inhibitory neuromuscular inputs not only in proximal colon, but also distal colon, long before the propagating contraction invades the distal region. During propulsion, wavelet analysis revealed increased coherence at ~2 Hz over large distances between the proximal and distal regions. Therefore, during propulsion, synchronous firing of descending inhibitory nerve pathways over long ranges aborally acts to suppress smooth muscle from contracting, counteracting the excitatory nerve pathways over this same region of colon. This delays muscle contraction downstream, ahead of the advancing contraction. The mechanism identified is more complex than expected and vastly different from fluid propulsion along other hollow smooth muscle organs like lymphatic vessels, portal vein, or ureters, that evolved without intrinsic neurons.

Novel intrinsic neurogenic and myogenic mechanisms underlying the formation of faecal pellets along the large intestine of guinea‐pigs

Publisher: Wiley

Date: 16-09-2021

DOI: 10.1113/JP282069

Abstract: Soft faecal material is transformed into discrete, pellet‐shaped faeces at the colonic flexure. Here, analysis of water content in natural faecal material revealed a decline from cecum to rectum without significant changes at the flexure. Thus, pellet formation is not explained by changes in viscosity alone. We then used video imaging of colonic wall movements with electromyography in isolated preparations containing guinea‐pig proximal colon, colonic flexure and distal colon. To investigate the pellet formation process, the colonic segments were infused with artificial contents (Krebs solution and 4–6% methylcellulose) to simulate physiological faecal content flow. Remarkably, pellet formation took place in vitro , without extrinsic neural inputs. Infusion evoked slowly propagating neurogenic contractions, the proximal colon migrating motor complexes (∼0.6 cpm), which initiated pellet formation at the flexure. Lesion of the flexure, but not the proximal colon, disrupted the formation of normal in idual pellets. In addition, a distinct myogenic mechanism was identified, whereby slow phasic contractions (∼1.9 cpm) initiated at the flexure and propagated short distances retrogradely into the proximal colon and antegradely into the distal colon. There were no detectable changes in the density or distribution of pacemaker‐type interstitial cells of Cajal across the flexure. The findings provide new insights into how solid faecal content is generated, suggesting the major mechanisms underlying faecal pellet formation involve the unique interaction at the colonic flexure between antegrade proximal colon migrating motor complexes, organized by enteric neurons, and retrograde myogenic slow phasic contractions. Additional, as yet unidentified extrinsic and/or humoral influences appear to contribute to processing of faecal content in vivo . image In herbivores, including guinea‐pigs, clearly defined faecal pellets are formed at a distinct location along the large intestine (colonic flexure). The mechanism underlying the formation of these faecal pellets at this region has remained unknown. We reveal a progressive and gradual reduction in water content of faecal content along the bowel. Hence, the distinct transition from amorphous to pellet shaped faecal content could not be explained by a dramatic increase in water reabsorption from a specific site. We discovered patterns of anterograde neurogenic and retrograde myogenic motor activity that facilitate the formation of faecal pellets. The formation of ‘pellet‐like’ boluses at the colonic flexure involves interaction of an antegrade migrating motor complex in the proximal colon and retrograde myogenic slow phasic contractions that emerge from the colonic flexure. The findings uncover intrinsic mechanisms responsible for the formation of discrete faecal scybala in the large intestine of a vertebrate.

Low-resolution colonic manometry leads to a gross misinterpretation of the frequency and polarity of propagating sequences: Initial results from fiber-optic high-resolution manometry studies

Publisher: Wiley

Date: 06-2013

DOI: 10.1111/NMO.12170

Abstract: High-resolution manometry catheters are now being used to record colonic motility. The aim of this study was to determine the influence of pressure sensor spacing on our ability to identify colonic propagating sequences (PS). Fiber-optic catheters containing 72-90 sensors spaced at 1 cm intervals were placed colonoscopically to the cecum in 11 patients with proven slow transit constipation, 11 patients with neurogenic fecal incontinence and nine healthy subjects. A 2 h section of trace from each subject was analyzed. Using the 1 cm spaced data as the gold standard, each data set was then sub-s led, by dropping channels from the data set to simulate sensor spacing of 10, 7, 5, 3, and 2 cm. In blinded fashion, antegrade and retrograde PS were quantified at each test sensor spacing. The data were compared to the PSs identified in the corresponding gold standard data set. In all subject groups as sensor spacing increased (i) the frequency of identified antegrade and retrograde PSs decreased (P < 0.0001) (ii) the ratio of antegrade to retrograde PSs increased (P < 0.0001) and (iii) the number of incorrectly labeled PSs increased (P < 0.003). Doubling the sensor spacing from 1 to 2 cm nearly halves the number of PSs detected. Tripling the sensor spacing from 1 to 3 cm resulted in a 30% chance of incorrectly labeling PSs. Closely spaced pressure recording sites (<2 cm) are mandatory to avoid gross misrepresentation of the frequency, morphology, and directionality of colonic propagating sequences.

Pudendal nerve injury impairs anorectal function and health related quality of life measures ≥2 years after 3D conformal radiotherapy for prostate cancer

Publisher: Informa UK Limited

Date: 15-11-2017

DOI: 10.1080/0284186X.2017.1400690

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

Publisher: Wiley

Date: 22-12-2011

DOI: 10.1111/J.1365-2982.2010.01651.X

Visual outcomes and quality of life before and after photorefractive keratectomy

Publisher: Medknow

Date: 2022

DOI: 10.4103/IJO.IJO_16_21

Transabdominal electrical stimulation increases colonic propagating pressure waves in paediatric slow transit constipation

Publisher: Elsevier BV

Date: 12-2012

DOI: 10.1016/J.JPEDSURG.2012.09.021

Abstract: In slow-transit constipation (STC) pancolonic manometry shows significantly reduced antegrade propagating sequences (PS) and no response to physiological stimuli. This study aimed to determine whether transcutaneous electrical stimulation using interferential current (IFC) applied to the abdomen increased colonic PS in STC children. Eight children (8-18 years) with confirmed STC had 24-h colonic manometry using a water-perfused, 8-channel catheter with 7.5 cm sidehole distance introduced via appendix stomas. They then received 12 sessions (20 min/3× per week) of IFC stimulation (2 paraspinal and 2 abdominal electrodes), applied at a comfortable intensity (<40 mA, carrier frequency 4 kHz, varying beat frequency 80-150 Hz). Colonic manometry was repeated 2 (n=6) and 7 (n=2) months after IFC. IFC significantly increased frequency of total PS/24h (mean ± SEM, pre 78 ± 34 vs post 210 ± 62, p=0.008, n=7), antegrade PS/24h (43 ± 16 vs 112 ± 20, p=0.01) and high litude PS (HAPS/24h, 5 ± 2:10 ± 3, p=0.04), with litude, velocity, or propagating distance unchanged. There was increased activity on waking and 4/8 ceased using antegrade continence enemas. Transcutaneous IFC increased colonic PS frequency in STC children with effects lasting 2-7 months. IFC may provide a treatment for children with treatment-resistant STC.

Research methodologies for the co‐production of knowledge for environmental management in Australia

Publisher: Informa UK Limited

Date: 12-2009

DOI: 10.1080/03014220909510581

Inference of mechanical states of intestinal motor activity using hidden Markov models

Publisher: Springer Science and Business Media LLC

Date: 12-2013

DOI: 10.1186/1472-6793-13-14

Abstract: Contractions and relaxations of the muscle layers within the digestive tract alter the external diameter and the internal pressures. These changes in diameter and pressure move digesting food and waste products. Defining these complex relationships is a fundamental step for neurogastroenterologists to be able define normal and abnormal gut motility. Utilising an in vitro technique that allows for the simultaneous recording of intraluminal pressure (manometry) and gut diameter (video) in an isolated section of rabbit colon, we developed a technique to help define the mechanical states of the muscle at any point in space and time during actual peristaltic movements. This was achieved by directly relating the changes in pressure to the changes in diameter along the length of the gut studied. For each in idual measure of pressure or diameter, 3 dynamic state components were identified increasing or decreasing changes or a stable period. Two additional static state components, fully contracted and fully distended, were defined for the diameter. Then qualitative mechanical states of the muscle activity were defined as combinations of these state components. A hidden Markov model was used to correlate adjacent-in-time s les, and the Viterbi algorithm was used to infer the most likely sequence of mechanical states based on the observed data. From this a spatiotemporal map of the mechanical states was produced, showing the regions of active contractions, active relaxations, or passive states along the length of the gut throughout the entire recording period. The identification of mechanical muscles states based on gut diameter and intraluminal pressure was possible by modelling muscle activation with a hidden Markov model.

Comparison of Different Binocular I Pad Games with Patching for Treatment of Amblyopia in Children: Pilot Study

Publisher: Science Publishing Group

Date: 2020

DOI: 10.11648/J.IJOVS.20200501.16

Measurement of anterior segment parameters in Saudi adults with myopia

Publisher: Medknow

Date: 07-2018

DOI: 10.1016/J.SJOPT.2018.04.007

Relationships between the results of anorectal investigations and symptom severity in patients with faecal incontinence

Publisher: Springer Science and Business Media LLC

Date: 06-07-2019

DOI: 10.1007/S00384-019-03331-0

Abstract: Anorectal dysfunction is the focus of diagnostic investigations for faecal incontinence. However, severity of incontinence and anorectal investigation results can be discordant. The aim of this study was to define the relationships between anorectal investigation results and incontinence severity to determine which measures, if any, were predictive of incontinence severity. Patients presenting for investigation of faecal incontinence completed a symptom questionnaire, anorectal manometry, rectal sensation, pudendal nerve terminal motor latency, and endoanal ultrasound. Bivariate analyses were conducted between the Jorge-Wexner score and investigation results. Subgroup analyses were performed for gender and symptom subtypes (urge, passive, mixed). A multiple regression analysis was performed. Five hundred and thirty-eight patients were included. There were weak correlations between the Jorge-Wexner score and maximal squeeze pressure [r = - 0.24, 95%CI(- 0.31, - 0.16), p < 0.001], and resting pressure [r = - 0.18, (95%CI(- 0.26, - 0.10), p < 0.001]. In men only, there were significant associations between the Jorge-Wexner score and endoanal sonography [IAS defects: t(113) = - 2.26, p = 0.03, d = 0.58, 95%CI(- 4.38, - 0.29)] and rectal sensation (MTV: r Anorectal investigations cannot predict the severity of faecal incontinence. This may be due to limitations of diagnostic modalities, the heterogeneity of anorectal dysfunction in these patients, or contributing factors which are extrinsic to the anorectum.

Novel insight into pressurization of the male and female urethra through application of a multi-channel fibre-optic pressure transducer: Proof of concept and validation

Publisher: XMLink

Date: 2020

DOI: 10.4111/ICU.20200059

Evaluation of the Waggoner computerized D15 color vision test using an iPad device

Publisher: Optica Publishing Group

Date: 18-10-2021

DOI: 10.1364/JOSAA.431987

Abstract: The W-D15 test, a computerized variant of the F-D15 test, is used to determine whether an in idual with a color vision defect can safely perform color-related tasks. This study evaluated the performance of the W-D15 test using an iPad. Fifty-nine color normal and 61 color vision defect subjects participated. Participants were screened based on the Ishihara, City University Test, and Waggoner PIP24 tests. Different failure criteria of the D15 tests were considered. The pass/failure agreement between the two tests was relatively appropriate, with a κ -coefficient ≥ 0.8 , for all failure criteria. The W-D15 could be an appropriate substitute for F-D15 using an iPad.

Anal Manometry: A Comparison of Techniques

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 07-2006

DOI: 10.1007/S10350-006-0549-7

Abstract: Methods of anal manometry vary between centers, resulting in potential difficulties in interpretation of results. This study compared several accepted manometric techniques in healthy control subjects and in patients with fecal incontinence. Eleven patients with fecal incontinence (M:F = 3:8 mean age = 67 years) and ten healthy control subjects (M:F = 3:7 mean age = 64 years) underwent anal manometry using five different methods: 1) water-perfused side hole 2) water-perfused end hole 3) microtransducer 4) microballoon 5) portable Peritron. Using a station pull-through technique, anal pressures (resting, squeeze, and cough pressures) were recorded at 1-cm intervals from rectum to anal verge, as well as radial pressures in four quadrants for Methods 1 and 2. Water perfusion side hole recorded slightly higher maximal resting pressures however, there were no significant differences between any of the methods. In healthy control subjects, distal maximal squeeze pressures were significantly higher (P < 0.05) than proximally as measured by microtransducer. There were slight (nonsignificant) variations in radial pressures with water perfusion and microtransducer. Peritron values for maximum resting pressure and maximum squeeze pressure were lower than those recorded by water perfusion side hole by a factor of 0.8. There is no significant variation in anal pressure recordings using standard manometry techniques. Variations in radial pressures are slight and not significant in clinical studies. Results obtained with portable nonperfusion systems must be interpreted appropriately.

24-hour colonic manometry inpediatric slow transit constipation shows significant reductions in antegrade propagation

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 08-2008

DOI: 10.1111/J.1572-0241.2008.01921.X

Abstract: The physiological basis of slow transit constipation (STC) in children remains poorly understood. We wished to examine pan-colonic motility in a group of children with severe chronic constipation refractory to conservative therapy. We performed 24 h pan-colonic manometry in 18 children (13 boys, 11.6 +/- 0.9 yr, range 6.6-18.7 yr) with scintigraphically proven STC. A water-perfused, balloon tipped, 8-channel, silicone catheter with a 7.5 cm intersidehole distance was introduced through a previously formed appendicostomy. Comparison data were obtained from nasocolonic motility studies in 16 healthy young adult controls and per-appendicostomy motility studies in eight constipated children with anorectal retention and/or normal transit on scintigraphy (non-STC). Antegrade propagating sequences (PS) were significantly less frequent (P < 0.01) in subjects with STC (29 +/- 4 per 24 h) compared to adult (53 +/- 4 per 24 h) and non-STC (70 +/- 14 per 24 h) subjects. High litude propagating sequences (HAPS) were of a normal frequency in STC subjects. Retrograde propagating sequences were significantly more frequent (P < 0.05) in non-STC subjects compared to STC and adult subjects. High litude retrograde propagating sequences were only identified in the STC and non-STC pediatric groups. The normal increase in motility index associated with waking and ingestion of a meal was absent in STC subjects. Prolonged pancolonic manometry in children with STC showed significant impairment in antegrade propagating motor activity and failure to respond to normal physiological stimuli. Despite this, HAPS occurred with normal frequency. These findings suggest significant clinical differences between STC in children and adults.

The effect of sacral nerve stimulation on distal colonic motility in patients with faecal incontinence

Publisher: Oxford University Press (OUP)

Date: 27-03-2013

DOI: 10.1002/BJS.9114

Abstract: Sacral nerve stimulation (SNS) is an effective treatment for neurogenic faecal incontinence (FI). However, the clinical improvement that patients experience cannot be explained adequately by changes in anorectal function. The aim of this study was to examine the effect of SNS on colonic propagating sequences (PSs) in patients with FI in whom urgency and incontinence was the predominant symptom. In patients with FI a high-resolution fibre-optic manometry catheter, containing 90 sensors spaced at 1-cm intervals, was positioned colonoscopically and clipped to the caecum. A unipolar or quadripolar tined electrode was implanted into the S3 sacral nerve foramen. Colonic manometry was evaluated in a double-blind randomized crossover trial, using true suprasensory stimulation or sham stimulation. Each stimulation period, lasting 2 h, was preceded by a 2-h basal manometric recording. All 11 patients studied showed a colonic response to SNS. In ten patients there was a significant increase in the frequency of retrograde PSs throughout the colon during true stimulation compared with sham stimulation (P = 0·014). In one outlier, with baseline retrograde PS frequency nine times that of the nearest patient, a reduction in retrograde PS frequency was recorded. Compared with sham stimulation, SNS had no effect on the frequency of antegrade PSs or high- litude PSs. SNS modulates colonic motility in patients with faecal urge incontinence. These data suggest that SNS may improve continence and urgency through alteration of colonic motility, particularly by increasing retrograde PSs in the left colon.

Fiber optic manometry catheters for in vivo monitoring of peristalsis in the human gut

Publisher: CRC Press

Date: 05-08-2022

DOI: 10.1201/B22316

New insights into neurogenic cyclic motor activity in the isolated guinea-pig colon

Publisher: Wiley

Date: 26-04-2017

DOI: 10.1111/NMO.13092

Abstract: The contents of the guinea pig distal colon consist of multiple pellets that move anally in a coordinated manner. This row of pellets results in continued distention of the colon. In this study, we have investigated quantitatively the features of the neurally dependent colonic motor patterns that are evoked by constant distension of the full length of guinea-pig colon. Constant distension was applied to the excised guinea-pig by high-resolution manometry catheters or by a series of hooks. Constant distension elicited regular Cyclic Motor Complexes (CMCs) that originated at multiple different sites along the colon and propagated in an oral or anal direction extending distances of 18.3±10.3 cm. CMCs were blocked by tetrodotoxin (TTX 0.6 μ mol L CMCs are a distinctive neurally dependent cyclic motor pattern, that emerge with distension over long lengths of the distal colon. They do not require changes in muscle tension or contractility to entrain the neural activity underlying CMC propagation. CMCs are likely to play an important role interacting with the neuromechanical processes that time the propulsion of multiple natural pellets and may be particularly relevant in conditions of impaction or obstruction, where long segments of colon are simultaneously distended.

Evaluation of the Third edition of the City University Colour Vision Test

Publisher: Wiley

Date: 08-11-2021

DOI: 10.1111/OPO.12915

Abstract: The 3rd edition of the City University Colour Vision Test (CUT) was originally based on the Farnsworth‐Munsell D‐15 test (D15). The first part of the test is for detecting a defect, and the second part is used to diagnose the type and severity of the defect. This study evaluates the CUT 3rd edition relative to the Ishihara and the D15 colour vision tests. Fifty nine colour vision normal subjects and 60 subjects with a congenital red‐green colour vision defect were recruited. Subjects were tested with the Ishihara and CUT tests. Subjects who failed the Ishihara also performed the D15 test. The agreement between the Ishihara and CUT screening plates was marginally higher when using the CUT failure criterion of error compared with using errors. If the diagnostic plates were included with the screening plates in determining the pass/fail outcomes, the agreement between the Ishihara and CUT was high, with a first‐order agreement coefficient (AC1) of 0.90. The AC1 coefficient agreement between the D15 and CUT diagnostic plates in terms of pass/fail was 0.81 when using the D15 failure criteria of or crossing. The level of agreement between the 3rd edition of the CUT and D15 was lower than the 2nd edition of the CUT. The primary reason for the lower agreement of the 3rd edition of the CUT was that it had a lower specificity relative to the D15 compared to the 2nd edition. Although the CUT predictive value for failing the D15 is over 90%, the predictive value for passing shows that 19%–25% of patients who pass the 3rd edition of the CUT test will fail the D15. The 3rd edition tends to misclassify protans as deutans or cannot classify the type of defect relative to the D15 and Ishihara.

Pudendal nerve injury in men with fecal incontinence after radiotherapy for prostate cancer

Publisher: Informa UK Limited

Date: 03-03-2015

DOI: 10.3109/0284186X.2015.1010693

ManoMap: an automated system for characterization of colonic propagating contractions recorded by high-resolution manometry

Publisher: Springer Science and Business Media LLC

Date: 26-01-2021

DOI: 10.1007/S11517-021-02316-Y

Neurogenic and myogenic motor patterns of rabbit proximal, mid, and distal colon

Publisher: American Physiological Society

Date: 07-2012

DOI: 10.1152/AJPGI.00429.2011

Abstract: The rabbit colon consists of four distinct regions. The motility of each region is controlled by myogenic and neurogenic mechanisms. Associating these mechanisms with specific motor patterns throughout all regions of the colon has not previously been achieved. Three sections of the colon (the proximal, mid, and distal colon) were removed from euthanized rabbits. The proximal colon consists of a triply teniated region and a single tenia region. Spatio-temporal maps were constructed from video recordings of colonic wall diameter, with associated intraluminal pressure recorded from the aboral end. Hexamethonium (100 μM) and tetrodotoxin (TTX 0.6 μM) were used to inhibit neural activity. Four distinct patterns of motility were detected: 1 myogenic and 3 neurogenic. The myogenic activity consisted of circular muscle (CM) contractions (ripples) that occurred throughout the colon and propagated in both antegrade (anal) and retrograde (oral) directions. The neural activity of the proximal colon consisted of slowly (0.1 mm/s) propagating colonic migrating motor complexes, which were abolished by hexamethonium. These complexes were observed in the region of the proximal colon with a single band of tenia. In the distal colon, tetrodotoxin-sensitive, thus neurally mediated, but hexamethonium-resistant, peristaltic (anal) and antiperistaltic (oral) contractions were identified. The distinct patterns of neurogenic and myogenic motor activity recorded from isolated rabbit colon are specific to each anatomically distinct region. The regional specificity motor pattern is likely to facilitate orderly transit of colonic content from semi-liquid to solid composition of feces.

Identification of multiple distinct neurogenic motor patterns that can occur simultaneously in the guinea pig distal colon

Publisher: American Physiological Society

Date: 2019

DOI: 10.1152/AJPGI.00256.2018

Abstract: In the guinea pig distal colon, nonpropulsive neurally mediated motor patterns have been observed in different experimental conditions. Isolated segments of guinea pig distal colon were used to investigate these neural mechanisms by simultaneously recording wall motion, intraluminal pressure, and smooth muscle electrical activity in different conditions of constant distension and in response to pharmacological agents. Three distinct neurally dependent motor patterns were identified: transient neural events (TNEs), cyclic motor complexes (CMC), and distal colon migrating motor complexes (DCMMC). These could occur simultaneously and were distinguished by their electrophysiological, mechanical, and pharmacological features. TNEs occurred at irregular intervals of ~3s, with bursts of action potentials at 9 Hz. They propagated orally at 12 cm/s via assemblies of ascending cholinergic interneurons that activated final excitatory and inhibitory motor neurons, apparently without involvement of stretch-sensitive intrinsic primary afferent neurons. CMCs occurred during maintained distension and consisted of clusters of closely spaced TNEs, which fused to cause high-frequency action potential firing at 7 Hz lasting ~10 s. They generated periodic pressure peaks mediated by stretch-sensitive intrinsic primary afferent neurons and by cholinergic interneurons. DCMMCs were generated by ongoing activity in excitatory motor neurons without apparent involvement of stretch-sensitive neurons, cholinergic interneurons, or inhibitory motor neurons. In conclusion, we have identified three distinct motor patterns that can occur concurrently in the isolated guinea pig distal colon. The mechanisms underlying the generation of these neural patterns likely involve recruitment of different populations of enteric neurons with distinct temporal activation properties.

Development and validation of the 21‐item Children's Vision for Living Scale (CVLS) by Rasch analysis

Publisher: Informa UK Limited

Date: 11-2013

DOI: 10.1111/CXO.12055

Abstract: The aim was to develop and validate an instrument called the 'Children's Vision for Living Scale' (CVLS) for the assessment of vision-related quality of life in Saudi Arabian children with and without amblyopia. A 43-item child self-report questionnaire was initially developed based on interviews with children with amblyopia, their parents and eye-care professionals, and a literature review. Following a process that involved the removal of redundant items, 28 items remained and were piloted on children aged five to 12 years with and without amblyopia (n = 48 amblyopic, n = 53 non-amblyopic) living in Saudi Arabia. Rasch analysis was applied to determine whether the 28-item questionnaire fitted the Rasch model. Rasch analysis was used to assess the validity and reliability of the questionnaire. Principal components analysis (PCA) was used to check dimensionality. A 21-item questionnaire resulting from this process was administered in children with (n = 81) and without (n = 82) amblyopia in Saudi Arabia for further validation. The final 21-item questionnaire had good validity and reliability as demonstrated by person separation of 2.02, person reliability of 0.80 (mean square and standard deviation: infit = 1.01 ± 0.39 outfit = 1.01 ± 0.40) and item reliability of 0.93 (item infit range = 1.33 to 0.78 item outfit range = 0.78 to 1.30). The mean difference between person and item scores of 0.33 ± 0.53 logits (scale range, 2 to -2) indicates that the items are well targeted to the populations. The PCA (dimensionality measures) shows the percentage of variance explained by measures equal to 26.4 per cent (modelled 26.9 per cent) and an eigenvalue of the first contrast of 2.5, which demonstrated good stability. The 21-item CVLS is a valid uni-dimensional child self-report instrument for the assessment of the impact of amblyopia on vision-related quality of life in children with and without amblyopia living in Saudi Arabia.

Upper esophageal sphincter mechanical states analysis: a novel methodology to describe UES relaxation and opening

Publisher: Frontiers Media SA

Date: 07-01-2015

DOI: 10.3389/FNSYS.2014.00241

Role of Oxidative Stress and Severity of Diabetic Retinopathy in Type 1 and Type 2 Diabetes

Publisher: S. Karger AG

Date: 2021

DOI: 10.1159/000514722

Abstract: b i Background: /i /b Diabetic retinopathy (DR) is a sight-threatening complication of diabetes mellitus (DM). Oxidative stress generated on account of hyperglycemic state may lead to retinal abnormalities including DR. b i Objectives: /i /b The aim of the study was to evaluate the status of antioxidant enzymes superoxide dismutase (SOD), and catalase (CAT), in different stages of DR severity in subjects with type 1 DM (T1DM) and type 2 DM (T2DM). b i Methods: /i /b The cross-sectional study enrolled 148 subjects with T1DM ( i n /i = 17), T2DM ( i n /i = 96), and nondiabetic controls ( i n /i = 35). Subjects with DM were ided into 2 subgroups based on DR severity (mild-to-severe nonproliferative DR [NPDR] and proliferative DR [PDR]), and serum glycated hemoglobin (HbA1c), lipid profile, SOD, and CAT were estimated. b i Results: /i /b Both SOD and CAT levels were lower in diabetic subjects than nondiabetic controls. A significant positive correlation was found between HbA1C level and severity of DR ( i /i & #x3c 0.0001). Levels of SOD and CAT varied significantly with DR severity in both diabetic groups at i /i & #x3c 0.05. Furthermore, levels of SOD and CAT were found to decrease significantly ( i /i & #x3c 0.001) in DR (+) compared to DR (−) patients. Also, increased levels of HbA1c were significantly associated ( i /i & #x3c 0.001) with decreased SOD in both subgroups (NPDR and PDR). DR severity was significantly associated with SOD and CAT in the NPDR and PDR subgroups ( i /i & #x3c 0.05). b i Conclusion: /i /b Oxidative stress and decreased antioxidant defenses are associated with DR progression to its PDR stage.

Childhood constipation: finally something is moving!

Publisher: Informa UK Limited

Date: 14-10-2015

DOI: 10.1586/17474124.2016.1098533

Abstract: Recent developments in the evaluation and treatment of childhood constipation are likely to influence the way we deal with pediatric defecation disorders in the near future. Innovations in both colonic and anorectal manometry are leading to novel insights into functional defecation disorders in children. Promising results have been achieved with innovative therapies such as electrical stimulation and new drugs with targets that differ from conventional pharmacological treatments. Also, new surgical approaches, guided by manometric findings, have led to improvement in patient outcome. Finally, utilization of non-pharmacological interventions such as fiber and probiotics has been a field of particular interest in recent years. The aim of this article is to provide an update on these and other novel diagnostic and therapeutic tools related to childhood constipation.

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

Publisher: Wiley

Date: 24-07-2018

DOI: 10.1111/NMO.13401

Abstract: 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. 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). 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. 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.

Faecal incontinence is associated with an impaired rectosigmoid brake and improved by sacral neuromodulation

Publisher: Wiley

Date: 19-07-2022

DOI: 10.1111/CODI.16249

Abstract: The rectosigmoid brake, characterised by retrograde cyclic motor patterns on high‐resolution colonic manometry, has been postulated as a contributor to the maintenance of bowel continence. Sacral neuromodulation (SNM) is an effective therapy for faecal incontinence, but its mechanism of action is unclear. This study aims to investigate the colonic motility patterns in the distal colon of patients with faecal incontinence, and how these are modulated by SNM. A high‐resolution fibreoptic colonic manometry catheter, containing 36 sensors spaced at 1‐cm intervals, was positioned in patients with faecal incontinence undergoing stage 1 SNM. One hour of pre‐ and post meal recordings were obtained followed by pre‐ and post meal recordings with suprasensory SNM. A 700‐kcal meal was given. Data were analysed to identify propagating contractions. Fifteen patients with faecal incontinence were analysed. Patients had an abnormal meal response (fewer retrograde propagating contractions compared to controls p = 0.027) and failed to show a post meal increase in propagating contractions (mean 17 ± 6/h premeal vs. 22 ± 9/h post meal, p = 0.438). Compared to baseline, SNM significantly increased the number of retrograde propagating contractions in the distal colon (8 ± 3/h premeal vs. 14 ± 3/h premeal with SNM, p = 0.028). Consuming a meal did not further increase the number of propagating contractions beyond the baseline upregulating effect of SNM. The rectosigmoid brake was suppressed in this cohort of patients with faecal incontinence. SNM may exert a therapeutic effect by modulating this rectosigmoid brake.

High-resolution impedance manometry characterizes the functional role of distal colonic motility in gas transit

Publisher: Wiley

Date: 02-06-2022

DOI: 10.1111/NMO.14178

Abstract: The colonic motor patterns associated with gas transit are poorly understood. This study describes the application of high‐resolution impedance manometry (HRiM) in the human colon in vivo to characterize distal colonic motility and gas transit (a) after a meal and (b) after intraluminal gas insufflation into the sigmoid colon. HRiM recordings were performed in 19 healthy volunteers, with sensors positioned from the distal descending colon to the proximal rectum. Protocol 1 (n = 10) compared pressure and impedance prior to and after a meal. Protocol 2 (n = 9) compared pressure and impedance before and after gas insufflation into the sigmoid colon (60 mL total volume). Both the meal and gas insufflation resulted in an increase in the prevalence of the 2‐8/minute “cyclic motor pattern” (meal: ( t (9) = −6.42, P .001) gas insufflation ( t (8) = −3.13, P = 0.01)), and an increase in the number of antegrade and retrograde propagating impedance events (meal: Z = −2.80, P = 0.005 gas insufflation Z = −2.67, P = 0.008). Propagating impedance events temporally preceded antegrade and retrograde propagating contractions, representing a column of luminal gas being displaced ahead of a propagating contraction. Three participants reported an urge to pass flatus and/or flatus during the studies. Initiation of the 2‐8/minute cyclic motor pattern in the distal colon occurs both following a meal and/or as a localized sensorimotor response to gas. The near‐absence of a flatal urge and the temporal association between propagating contractions and gas transit supports the hypothesis that the 2‐8/minute cyclic motor pattern acts as a physiological “brake” modulating rectal filling.

The “rectosigmoid brake”: Review of an emerging neuromodulation target for colorectal functional disorders

Publisher: Wiley

Date: 28-06-2017

DOI: 10.1111/1440-1681.12760

Abstract: The regulation of gastrointestinal motility encompasses several overlapping mechanisms including highly regulated and coordinated neurohormonal circuits. Various feedback mechanisms or "brakes" have been proposed. While duodenal, jejunal, and ileal brakes are well described, a putative distal colonic brake is less well defined. Despite the high prevalence of colonic motility disorders, there is little knowledge of colonic motility owing to difficulties with organ access and technical difficulties in recording detailed motor patterns along its entire length. The motility of the colon is not under voluntary control. A wide range of motor patterns is seen, with long intervals of intestinal quiescence between them. In addition, the use of traditional manometric catheters to record contractile activity of the colon has been limited by the low number of widely spaced sensors, which has resulted in the misinterpretation of colonic motor patterns. The recent advent of high-resolution (HR) manometry is revolutionising the understanding of gastrointestinal motor patterns. It has now been observed that the most common motor patterns in the colon are repetitive two to six cycles per minute (cpm) propagating events in the distal colon. These motor patterns are prominent soon after a meal, originate most frequently in the rectosigmoid region, and travel in the retrograde direction. The distal prominence and the origin of these motor patterns raise the possibility of them serving as a braking mechanism, or the "rectosigmoid brake," to limit rectal filling. This review aims to describe what is known about the "rectosigmoid brake," including its physiological and clinical significance and potential therapeutic applications.

Exploring the dark continent with fibre Bragg gratings

Publisher: SPIE

Date: 02-06-2014

DOI: 10.1117/12.2059057

Urinary p75ECD A prognostic, disease progression, and pharmacodynamic biomarker in ALS

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 22-02-2017

DOI: 10.1212/WNL.0000000000003741

Abstract: To evaluate urinary neurotrophin receptor p75 extracellular domain (p75 ECD ) levels as disease progression and prognostic biomarkers in amyotrophic lateral sclerosis (ALS). The population in this study comprised 45 healthy controls and 54 people with ALS, 31 of whom were s led longitudinally. Urinary p75 ECD was measured using an enzyme-linked immunoassay and validation included intra-assay and inter-assay coefficients of variation, effect of circadian rhythm, and stability over time at room temperature, 4°C, and repeated freeze-thaw cycles. Longitudinal changes in urinary p75 ECD were examined by mixed model analysis, and the prognostic value of baseline p75 ECD was explored by survival analysis. Confirming our previous findings, p75 ECD was higher in patients with ALS (5.6 ± 2.2 ng/mg creatinine) compared to controls (3.6 ± 1.4 ng/mg creatinine, p 0.0001). Assay reproducibility was high, with p75 ECD showing stability across repeated freeze-thaw cycles, at room temperature and 4°C for 2 days, and no diurnal variation. Urinary p75 ECD correlated with the revised ALS Functional Rating Scale at first evaluation ( r = −0.44, p = 0.008) and across all study visits ( r = −0.36, p 0.0001). p75 ECD also increased as disease progressed at an average rate of 0.19 ng/mg creatinine per month ( p 0.0001). In multivariate prognostic analysis, bulbar onset (hazard ratio [HR] 3.0, p = 0.0035), rate of disease progression from onset to baseline (HR 4.4, p 0.0001), and baseline p75 ECD (HR 1.3, p = 0.0004) were predictors of survival. The assay for urinary p75 ECD is analytically robust and shows promise as an ALS biomarker with prognostic, disease progression, and potential pharmacodynamic application. Baseline urinary p75 ECD provides prognostic information and is currently the only biological fluid–based biomarker of disease progression.

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

Publisher: Wiley

Date: 09-2009

DOI: 10.1111/J.1365-2982.2009.01323.X

Abstract: Available evidence implicates abnormal colonic contractility in patients suffering from constipation. Traditional analysis of colonic manometry focuses on the frequency, extent and litude 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.

Measurement of the longitudinal and circumferential muscular activity associated with peristalsis using a single fibre grating array

Publisher: SPIE

Date: 08-09-2010

DOI: 10.1117/12.866307

Grapefruit Extract-Mediated Fabrication of Photosensitive Aluminum Oxide Nanoparticle and Their Antioxidant and Anti-Inflammatory Potential

Publisher: MDPI AG

Date: 31-05-2022

DOI: 10.3390/NANO12111885

Abstract: Aluminum oxide nanoparticles (Al2O3 NPs) were synthesized using a simple, eco-friendly green synthesis approach in an alkaline medium from the extract of grapefruit peel waste. The pre-synthesized, nano-crystalline Al2O3 NPs were characterized by using spectroscopic (UV–vis, FTIR, XRD, and EDX) and microscopic (SEM and TEM) techniques. The formed Al2O3 NPs exhibited a pronounced absorption peak at 278 nm in the UV–vis spectrum. The average particle size of the as-prepared Al2O3 NPs was evaluated to be 57.34 nm, and the atomic percentages of O and Al were found to be 54.58 and 45.54, respectively. The fabricated Al2O3 NPs were evaluated for antioxidant, anti-inflammatory, and immunomodulatory properties. The Al2O3 NPs showed strong antioxidant potential towards all the four tested assays. The anti-inflammatory and immunomodulatory potential of Al2O3 NPs was investigated by measuring the production of nitric oxide and superoxide anion (O2•−), as well as proinflammatory cytokines tumour necrosis factor (TNF-α, IL-6) and inhibition of nuclear factor kappa B (NF- κB). The results revealed that Al2O3 NPs inhibited the production of O2•− (99.4%) at 100 μg mL−1 concentrations and intracellular NO•− (55%), proinflammatory cytokines IL-6 (83.3%), and TNF-α (87.9%) at 50 μg mL−1 concentrations, respectively. Additionally, the Al2O3 NPs inhibited 41.8% of nuclear factor kappa B at 20 μg mL−1 concentrations. Overall, the outcomes of current research studies indicated that Al2O3 NPs possess anti-inflammatory and immunomodulatory properties and could be used to treat chronic and acute anti-inflammatory conditions.

High-resolution anatomic correlation of cyclic motor patterns in the human colon: Evidence of a rectosigmoid brake

Publisher: American Physiological Society

Date: 05-2017

DOI: 10.1152/AJPGI.00021.2017

Abstract: Colonic cyclic motor patterns (CMPs) have been hypothesized to act as a brake to limit rectal filling. However, the spatiotemporal profile of CMPs, including anatomic origins and distributions, remains unclear. This study characterized colonic CMPs using high-resolution (HR) manometry (72 sensors, 1-cm resolution) and their relationship with proximal antegrade propagating events. Nine healthy volunteers were recruited. Recordings were performed over 4 h, with a 700-kcal meal given after 2 h. Propagating events were visually identified and analyzed by pattern, origin, litude, extent of propagation, velocity, and duration. Manometric data were normalized using anatomic landmarks identified on abdominal radiographs. These were mapped over a three-dimensional anatomic model. CMPs comprised a majority of detected propagating events. Most occurred postprandially and were retrograde propagating events (84.9 ± 26.0 retrograde vs. 14.3 ± 11.8 antegrade events/2 h, P = 0.004). The dominant sites of initiation for retrograde CMPs were in the rectosigmoid region, with patterns proximally propagating by a mean distance of 12.4 ± 0.3 cm. There were significant differences in the characteristics of CMPs depending on the direction of travel and site of initiation. Association analysis showed that proximal antegrade propagating events occurred independently of CMPs. This study accurately characterized CMPs with anatomic correlation. CMPs were unlikely to be triggered by proximal antegrade propagating events in our study context. However, the distal origin and prominence of retrograde CMPs could still act as a mechanism to limit rectal filling and support the theory of a “rectosigmoid brake.” NEW & NOTEWORTHY Retrograde cyclic motor patterns (CMPs) are the dominant motor patterns in a healthy prepared human colon. The major sites of initiation are in the rectosigmoid region, with retrograde propagation, supporting the idea of a “rectosigmoid brake.” A significant increase in the number of CMPs is seen after a meal. In our study context, the majority of CMPs occurred independent of proximal propagating events, suggesting that CMPs are primarily controlled by external innervation.

A Novel Method for Electrophysiological Analysis of EMG Signals Using MesaClip

Publisher: Frontiers Media SA

Date: 09-06-2020

DOI: 10.3389/FPHYS.2020.00484

Chronic constipation

Publisher: Springer Science and Business Media LLC

Date: 14-12-2017

DOI: 10.1038/NRDP.2017.95

Abstract: Chronic constipation is a prevalent condition that severely impacts the quality of life of those affected. Several types of primary chronic constipation, which show substantial overlap, have been described, including normal-transit constipation, rectal evacuation disorders and slow-transit constipation. Diagnosis of primary chronic constipation involves a multistep process initiated by the exclusion of 'alarm' features (for ex le, unintentional weight loss or rectal bleeding) that might indicate organic diseases (such as polyps or tumours) and a therapeutic trial with first-line treatments such as dietary changes, lifestyle modifications and over-the-counter laxatives. If symptoms do not improve, investigations to diagnose rectal evacuation disorders and slow-transit constipation are performed, such as digital rectal examination, anorectal structure and function testing (including the balloon expulsion test, anorectal manometry or defecography) or colonic transit tests (such as the radiopaque marker test, wireless motility capsule test, scintigraphy or colonic manometry). The mainstays of treatment are diet and lifestyle interventions, pharmacological therapy and, rarely, surgery. This Primer provides an introduction to the epidemiology, pathophysiological mechanisms, diagnosis, management and quality of life associated with the commonly encountered clinical problem of chronic constipation in adults unrelated to opioid abuse.

Chronic constipation in adults: Contemporary perspectives and clinical challenges. 1: Epidemiology, diagnosis, clinical associations, pathophysiology and investigation

Publisher: Wiley

Date: 02-12-2020

DOI: 10.1111/NMO.14050

Abstract: Chronic constipation is a prevalent disorder that affects patients' quality of life and consumes resources in healthcare systems worldwide. In clinical practice, it is still considered a challenge as clinicians frequently are unsure as to which treatments to use and when. Over a decade ago, a Neurogastroenterology & Motility journal supplement devoted to the investigation and management of constipation was published (2009 21 (Suppl.2)). This included seven articles, disseminating all themes covered during a preceding 2‐day meeting held in London, entitled “Current perspectives in chronic constipation: a scientific and clinical symposium.” In October 2018, the 3rd London Masterclass, entitled “Contemporary management of constipation” was held, again over 2 days. All faculty members were invited to author two new review articles, which represent a collective synthesis of talks presented and discussions held during this meeting. This article represents the first of these reviews, addressing epidemiology, diagnosis, clinical associations, pathophysiology, and investigation. Clearly, not all aspects of the condition can be covered in adequate detail hence, there is a focus on particular “hot topics” and themes that are of contemporary interest. The second review addresses management of chronic constipation, covering behavioral, conservative, medical, and surgical therapies.

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

Publisher: Wiley

Date: 04-2000

DOI: 10.1046/J.1365-2982.2000.00187.X

Abstract: 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 Nw-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.

Coexistent faecal incontinence and constipation: A cross-sectional study of 4027 adults undergoing specialist assessment

Publisher: Elsevier BV

Date: 10-2020

DOI: 10.1016/J.ECLINM.2020.100572

A framework for the resilience of seagrass ecosystems

Publisher: Elsevier BV

Date: 11-2015

DOI: 10.1016/J.MARPOLBUL.2015.08.016

Changes in specific esophageal neuromechanical wall states are associated with conscious awareness of a solid swallowed bolus in healthy subjects

Publisher: American Physiological Society

Date: 05-2020

DOI: 10.1152/AJPGI.00235.2019

Abstract: This study explores esophageal neuromechanical wall states derived from changes in pressure and impedance-derived distension in relation to conscious awareness of esophageal solid bolus transit in healthy volunteers. There are increases in neuromechanical wall states indicative of esophageal distension in healthy volunteers with conscious awareness of bolus transit as compared with unaware in iduals. Bolus-based esophageal distension is postulated as a mechanism for esophageal symptoms such as dysphagia.

Randomised, placebo‐controlled trial and meta‐analysis show benefit of ondansetron for irritable bowel syndrome with diarrhoea: The TRITON trial

Publisher: Wiley

Date: 03-03-2023

DOI: 10.1111/APT.17426

Abstract: Ondansetron may be beneficial in irritable bowel syndrome with diarrhoea (IBS‐D). To conduct a 12‐week parallel group, randomised, double‐blind, placebo‐controlled trial of ondansetron 4 mg o.d. (titrated up to 8 mg t.d.s.) in 400 IBS‐D patients. Primary endpoint: % responders using the Food and Drug Administration (FDA) composite endpoint. Secondary and mechanistic endpoints included stool consistency (Bristol Stool Form Scale) and whole gut transit time (WGTT). After literature review, results were pooled with other placebo‐controlled trials in a meta‐analysis to estimate relative risks (RR), 95% confidence intervals (CIs) and number needed to treat (NNT). Eighty patients were randomised. On intention‐to‐treat analysis, 15/37 (40.5% 95% CI 24.7%–56.4%) met the primary endpoint on ondansetron versus 12/43 (27.9% 95% CI 14.5%–41.3%) on placebo ( p = 0.19). Ondansetron improved stool consistency compared with placebo (adjusted mean difference − 0.7 95% CI −1.0 to−0.3, p 0.001). Ondansetron increased WGTT between baseline and week 12 (mean (SD) difference 3.8 (9.1) hours, versus placebo −2.2 (10.3) hours, p = 0.01). Meta‐analysis of 327 patients from this, and two similar trials, demonstrated ondansetron was superior to placebo for the FDA composite endpoint (RR of symptoms not responding = 0.86 95% CI 0.75–0.98, NNT = 9) and stool response (RR = 0.65 95% CI 0.52–0.82, NNT = 5), but not abdominal pain response (RR = 0.95 95% CI 0.74–1.20). Although small numbers meant the primary endpoint was not met in this trial, when pooled with other similar trials meta‐analysis suggests ondansetron improves stool consistency and reduces days with loose stool and urgency. Trial registration – www.isrctn.com/ISRCTN17508514

Advances in the diagnosis and classification of gastric and intestinal motility disorders

Publisher: Springer Science and Business Media LLC

Date: 06-04-2018

DOI: 10.1038/NRGASTRO.2018.7

Post-Operative Anorectal Manometry in Children following Anorectal Malformation Repair: A Systematic Review

Publisher: MDPI AG

Date: 28-03-2023

DOI: 10.3390/JCM12072543

Abstract: Despite surgical correction, children with anorectal malformations may experience long-term bowel dysfunction, including fecal incontinence and/or disorders of evacuation. Anorectal manometry is the most widely used test of anorectal function. Although considerable attention has been devoted to its application in the anorectal malformation cohort, there have been few attempts to consolidate the findings obtained. This systematic review aimed to (1) synthesize and evaluate the existing data regarding anorectal manometry results in children following anorectal malformation repair, and (2) evaluate the manometry protocols utilized, including equipment, assessment approach, and interpretation. We reviewed four databases (Embase, MEDLINE, the Cochrane Library, and PubMed) for relevant articles published between 1 January 1985 and 10 March 2022. Studies reporting post-operative anorectal manometry in children ( years) following anorectal malformation repair were evaluated for eligibility. Sixty-three studies were eligible for inclusion. Of the combined total cohort of 2155 patients, anorectal manometry results were reported for 1755 children following repair of anorectal malformations. Reduced resting pressure was consistently identified in children with anorectal malformations, particularly in those with more complex malformation types and/or fecal incontinence. Significant variability was identified in relation to manometry equipment, protocols, and interpretation. Few studies provided adequate cohort medical characteristics to facilitate interpretation of anorectal manometry findings within the context of the broader continence mechanism. This review highlights a widespread lack of standardization in the anorectal manometry procedure used to assess anorectal function in children following anorectal malformation repair. Consequently, interpretation and comparison of findings, both within and between institutions, is exceedingly challenging, if not impossible. Standardized manometry protocols, accompanied by a consistent approach to analysis, including definitions of normality and abnormality, are essential to enhance the comparability and clinical relevance of results.

Coexistent faecal incontinence and constipation: Common but frequently overlooked

Publisher: Wiley

Date: 06-2022

DOI: 10.1002/UEG2.12263

Does exertional heat stress impact gastrointestinal function and symptoms?

Publisher: Elsevier BV

Date: 12-2022

DOI: 10.1016/J.JSAMS.2022.10.008

Abstract: Exertional-heat stress generates a thermoregulatory strain that exacerbates splanchnic hypoperfusion and sympathetic drive, but the effects on gastrointestinal function are poorly defined. The study aimed to determine the effects of exertional-heat stress on gastric myoelectrical activity, orocecal transit time (OCTT), and gastrointestinal symptoms (GIS). Randomised cross-over study. Endurance runners (n = 16) completed 2 h of running at 60 % V̇O Post-exercise T Running for 2 h at 60 % V̇O

The relationship between residual sphincter damage after primary repair, faecal incontinence, and anal sphincter function in primiparous women with an obstetric anal sphincter injury

Publisher: Wiley

Date: 02-11-2018

DOI: 10.1002/NAU.23826

Abstract: Anal sphincter injury has been identified as a primary cause of post-partum fecal incontinence in women with obstetric anal sphincter injury. However, women without obstetric anal sphincter injury may also develop fecal incontinence. The aim is to determine the relationship between fecal incontinence severity and i) residual anal sphincter injury, quantified by the Starck score, and ii) anal sphincter tone. Consecutive case series of prospectively collected data set in a Pelvic Floor Unit within a tertiary teaching hospital in Australia. Population 181 primiparous women with Sultan classification Grade 3 and 4 sphincter injuries. Sultan classification, anal manometry, pudendal nerve terminal motor latency, St Mark's fecal incontinence score, and Starck ultrasound score. 45% of women reported some degree of fecal incontinence. One third of women with normal external sphincter tone were incontinent. Those with higher Starck score had higher St Mark's scores. A higher Sultan classification correlated with more severe incontinence regardless if the repair was complete. Forceps delivery had a twofold risk of incontinence when compared to non-forceps delivery. The importance of an effective anal sphincter repair is confirmed. However, overall there is no direct relationship between residual sphincter damage, anal sphincter tone, and fecal incontinence severity. These data indicate that anal sphincter integrity alone is not the sole mechanism for maintaining fecal continence. Rectal and colonic motor function may also play a role and investigation into these components may provide greater insight into the effect of vaginal delivery upon fecal continence mechanisms.

Factor analysis identifies subgroups of constipation

Publisher: Baishideng Publishing Group Inc.

Date: 2011

DOI: 10.3748/WJG.V17.I11.1468

Manometry of the Human Ileum and Ileocaecal Junction in Health, Disease and Surgery: A Systematic Review

Publisher: Frontiers Media SA

Date: 15-04-2020

DOI: 10.3389/FSURG.2020.00018

Investigating the relationships between peristaltic contraction and fluid transport in the human colon using Smoothed Particle Hydrodynamics

Publisher: Elsevier BV

Date: 04-2012

DOI: 10.1016/J.COMPBIOMED.2012.01.002

Abstract: Complex relationships exist between gut contractility and the flow of digesta. We propose here a Smoothed Particle Hydrodynamics model coupling the flow of luminal content and wall flexure to help investigate these relationships. The model indicates that a zone of muscular relaxation preceding the contraction is an important element for transport. Low pressures in this zone generate positive thrust for low viscosity content. The viscosity of luminal content controls the localization of the flow and the magnitude of the radial pressure gradient and together with contraction litude they control the transport rate. For high viscosity content, high lumen occlusion is required for effective propulsion.

Colonic Manometry

Publisher: Elsevier

Date: 2020

DOI: 10.1016/B978-0-12-801238-3.66005-1

A systematic review of sacral nerve stimulation mechanisms in the treatment of fecal incontinence and constipation

Publisher: Wiley

Date: 28-08-2014

DOI: 10.1111/NMO.12388

Abstract: Sacral nerve stimulation (SNS) is now well established as a treatment for fecal incontinence (FI) resistant to conservative measures and may also have utility in the management of chronic constipation however, mechanism of action is not fully understood. End organ effects of SNS have been studied in both clinical and experimental settings, but interpretation is difficult due to the multitude of techniques used and heterogeneity of reported findings. The aim of this study was to systematically review available evidence on the mechanisms of SNS in the treatment of FI and constipation. Two systematic reviews of the literature (performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses framework) were performed to identify manuscripts pertaining to (a) clinical and (b) physiological effects of SNS during the management of hindgut dysfunction. The clinical literature search revealed 161 articles, of which 53 were deemed suitable for analysis. The experimental literature search revealed 43 articles, of which nine were deemed suitable for analysis. These studies reported results of investigative techniques examining changes in cortical, gastrointestinal, colonic, rectal, and anal function. The initial hypothesis that the mechanism of SNS was primarily peripheral motor neurostimulation is not supported by the majority of recent studies. Due to the large body of evidence demonstrating effects outside of the anorectum, it appears likely that the influence of SNS on anorectal function occurs at a pelvic afferent or central level.

Assessment of visual function and Vision-related Quality of Life in female contact lens wearers with Dry Eye Syndrome

Publisher: Medknow

Date: 07-2018

DOI: 10.1016/J.SJOPT.2018.03.001

Distinct patterns of myogenic motor activity identified in isolated human distal colon with high‐resolution manometry

Publisher: Wiley

Date: 06-05-2020

DOI: 10.1111/NMO.13871

Pancolonic motor response to subsensory and suprasensory sacral nerve stimulation in patients with slow-transit constipation

Publisher: Oxford University Press (OUP)

Date: 03-05-2012

DOI: 10.1002/BJS.8760

Abstract: Sacral nerve stimulation (SNS) is emerging as a potential treatment for patients with constipation. Although SNS can elicit an increase in colonic propagating sequences (PSs), the optimal stimulus parameters for this response remain unknown. This study evaluated the colonic motor response to subsensory and suprasensory SNS in patients with slow-transit constipation. Patients with confirmed slow-transit constipation were studied. Either a water-perfused manometry catheter or a high-resolution fibre-optic manometry catheter was positioned colonoscopically to the caecum. A temporary electrode was implanted transcutaneously in the S3 sacral nerve foramen. In the fasted state, three conditions were evaluated in a double-blind randomized fashion: sham, subsensory and suprasensory stimulation. Each 2-h treatment period was preceded by a 2-h basal period. The delta (Δ) value was calculated as the frequency of the event during stimulation minus that during the basal period. Nine patients had readings taken with a water-perfused catheter and six with a fibre-optic catheter. Compared with sham stimulation, suprasensory stimulation caused a significant increase in the frequency of PSs (mean(s.d.) Δ value − 1·1(7·2) versus 6·1(4·0) PSs per 2 h P = 0·004). No motor response was recorded in response to subsensory stimulation compared with sham stimulation. Compared with subsensory stimulation, stimulation at suprasensory levels caused a significant increase in the frequency of PSs (P = 0·006). In patients with slow-transit constipation, suprasensory SNS increased the frequency of colonic PSs, whereas subsensory SNS stimulation did not. This has implications for the design of therapeutic trials and the clinical application of the device.

Characterization of alternating neurogenic motor patterns in mouse colon

Publisher: Wiley

Date: 30-11-2021

DOI: 10.1111/NMO.14047

Abstract: Colonic motor complexes (CMCs) have been widely recorded in the large intestine of vertebrates. We have investigated whether in the smooth muscle, a single unified pattern of electrical activity, or different patterns of electrical activity give rise to the different neurogenic patterns of motility underlying CMCs in vitro. To study differences of the CMCs between proximal and distal colon, we used a novel combination of techniques to simultaneously record muscle diameter and force at multiple sites along the whole mouse colon ex vivo. In addition, electrical activity of smooth muscle was recorded by suction electrodes. Two distinct types of CMCs were distinguished CMCs that propagated along the entire colon (complete CMC) and CMCs which were restricted to the proximal colon (incomplete CMC). The two types of CMC often occurred in the same preparations. Incomplete CMCs had longer bursts of smooth muscle action potentials than complete CMCs and propagated more slowly. Interestingly, both types of CMC were associated with similar frequency bursts of smooth muscle action potentials at ~2.4 Hz. In the most proximal colon, an additional firing frequency was detected close to ~7 Hz generating multiple peaks within each CMC. We report distinct characteristics underlying complete and incomplete CMCs in isolated mouse colon. Recognizing these distinct patterns of motility will be important for future interpretation of analysis of murine colonic motility recordings. The identification of alternating patterns of motor activity in proximal colon, but not distal colon may reflect specific neural mechanisms for fecal pellet formation.

Post‐operative colonic manometry in children with Hirschsprung disease: A systematic review

Publisher: Wiley

Date: 02-07-2021

DOI: 10.1111/NMO.14201

Abstract: A significant proportion of children experience bowel dysfunction (including constipation and fecal incontinence) following surgical repair of Hirschsprung disease (HD). Persistent symptoms are thought to relate to underlying colonic and/or anorectal dysmotility. Manometry may be used to investigate the gastrointestinal motility patterns of this population. To (1) evaluate the colonic manometry equipment and protocols used in the assessment of the post‐operative HD population and (2) summarize the available evidence regarding colonic motility patterns in children with HD following surgical repair. We performed a systematic review of the Cochrane Library, Embase, MEDLINE, and PubMed databases (January 1, 1980 and March 9, 2020). Data were extracted independently by two authors. This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA). Studies reporting the post‐operative assessment of children with HD using colonic manometry were considered for inclusion. Five studies satisfied selection criteria, providing a combined total of 496 children. Of these, 184 children with repaired HD underwent colonic manometry. Studies assessed heterogeneous populations, utilized variable manometry equipment and protocols, and reported limited baseline symptom characteristics, thus restricting comparability. All studies used low‐resolution colonic manometry. This systematic review highlighted the paucity of evidence informing the understanding of colonic dysmotility in the post‐operative HD cohort. Current literature is limited by variable methodologies, heterogeneous cohorts, and the lack of high‐resolution manometry.

Design of a high-sensor count fibre optic manometry catheter for in-vivo colonic diagnostics

Publisher: The Optical Society

Date: 23-11-2009

DOI: 10.1364/OE.17.022423

Postoperative ileus—An ongoing conundrum

Publisher: Wiley

Date: 30-11-2021

DOI: 10.1111/NMO.14046

Abstract: Postoperative ileus is common and is a major clinical problem. It has been widely studied in patients and in experimental models in laboratory animals. A wide variety of treatments have been tested to prevent or modify the course of this disorder. This review draws together information on animal studies of ileus with studies on human patients. It summarizes some of the conceptual advances made in understanding the mechanisms that underlie paralytic ileus. The treatments that have been tested in human subjects (both pharmacological and non-pharmacological) and their efficacy are summarized and graded consistent with current clinical guidelines. The review is not intended to provide a comprehensive overview of ileus, but rather a general understanding of the major clinical problems associated with it, how animal models have been useful to elucidate key mechanisms and, finally, some perspectives from both scientists and clinicians as to how we may move forward with this debilitating yet common condition.

The effects of loperamide on excitatory and inhibitory neuromuscular function in the human colon

Publisher: Wiley

Date: 21-08-2022

DOI: 10.1111/NMO.14442

Abstract: In most animal species, opioids alter colonic motility via the inhibition of excitatory enteric motor neurons. The mechanisms by which opioids alter human colonic motility are unclear. The aim of this study was to describe the effects of loperamide on neuromuscular function in the human colon. Tissue specimens of human colon from 10 patients undergoing an anterior resection were ided into three inter‐taenial circular muscle strips. Separate organ baths were used to assess: (1) excitatory transmission (selective blockade of inhibitory transmission: L‐NOARG/MRS2179) (2) inhibitory transmission (selective blockade of excitatory transmission: hyoscine hydrobromide) and (3) a control bath (no drug additions). Neuromuscular function was assessed using force transducer recordings and electrical field stimulation (EFS 20 V, 10 Hz, 0.5 ms, 10 s) prior to and following loperamide and naloxone. In human preparations with L‐NOARG/MRS2179, loperamide had no significant effects on isometric contractions. In preparations with hyoscine hydrobromide, loperamide reduced isometric relaxation during EFS (median difference + 0.60 g post‐loperamide, Z = −2.35, p = 0.019). Loperamide had no effect on excitatory neuromuscular function in human colonic circular muscle. These findings suggest that loperamide alters colonic function by acting primarily on inhibitory motor neurons, premotor enteric neurons, or via alternative non‐opioid receptor pathways.

Colonic and anorectal motility testing in the high-resolution era

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 2016

DOI: 10.1097/MOG.0000000000000229

Sacral Nerve Stimulation Fails to Offer Long-term Benefit in Patients With Slow-Transit Constipation

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 09-2016

DOI: 10.1097/DCR.0000000000000653

Abstract: Sacral nerve stimulation is proposed as a treatment for slow-transit constipation. However, in our randomized controlled trial we found no therapeutic benefit over sham stimulation. These patients have now been followed-up over a long-term period. The purpose of this study was to assess the long-term efficacy of sacral nerve stimulation in patients with scintigraphically confirmed slow-transit constipation. This study was designed for long-term follow-up of patients after completion of a randomized controlled trial. It was conducted at an academic tertiary public hospital in Sydney. Adults with slow-transit constipation were included. At the 1- and 2-year postrandomized controlled trial, the primary treatment outcome measure was the proportion of patients who reported a feeling of complete evacuation on days per week for ≥2 of 3 weeks during stool diary assessment. Secondary outcome was demonstration of improved colonic transit at 1 year. Fifty-three patients entered long-term follow-up, and 1 patient died. Patient dissatisfaction or serious adverse events resulted in 44 patients withdrawing from the study because of treatment failure by the end of the second year. At 1 and 2 years, 10 (OR = 18.8% (95% CI, 8.3% to 29.3%)) and 3 patients (OR = 5.7% (95% CI, –0.5% to 11.9%)) met the primary outcome measure. Colonic isotope retention at 72 hours did not differ between baseline (OR = 75.6% (95% CI, 65.7%–85.6%)) and 1-year follow-up (OR = 61.7% (95% CI, 47.8%–75.6%)). This study only assessed patients with slow-transit constipation. In these patients with slow-transit constipation, sacral nerve stimulation was not an effective treatment.

Characterization of Esophageal Physiology Using Mechanical State Analysis

Publisher: Frontiers Media SA

Date: 17-02-2016

DOI: 10.3389/FNSYS.2016.00010

Screening for VACTERL Anomalies in Children with Anorectal Malformations: Outcomes of a Standardized Approach

Publisher: Elsevier BV

Date: 07-2023

DOI: 10.1016/J.JPEDSURG.2023.01.051

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

Publisher: Wiley

Date: 09-2008

DOI: 10.1111/J.1365-2982.2008.01147.X

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.

Design and clinical results from a fibre optic manometry catheter for oesophageal motility studies

Publisher: SPIE

Date: 14-04-2008

DOI: 10.1117/12.785968

Stimulation of extrinsic sympathetic nerves differentially affects neurogenic motor activity in guinea pig distal colon

Publisher: Wiley

Date: 2023

DOI: 10.14814/PHY2.15567

Abstract: The speed of pellet propulsion through the isolated guinea pig distal colon in vitro significantly exceeds in vivo measurements, suggesting a role for inhibitory mechanisms from sources outside the gut. The aim of this study was to investigate the effects of sympathetic nerve stimulation on three different neurogenic motor behaviors of the distal colon: transient neural events (TNEs), colonic motor complexes (CMCs), and pellet propulsion. To do this, segments of guinea pig distal colon with intact connections to the inferior mesenteric ganglion (IMG) were set up in organ baths allowing for simultaneous extracellular suction electrode recordings from smooth muscle, video recordings for diameter mapping, and intraluminal manometry. Electrical stimulation (1–20 Hz) of colonic nerves surrounding the inferior mesenteric artery caused a statistically significant, frequency‐dependent inhibition of TNEs, as well as single pellet propulsion, from frequencies of 5 Hz and greater. Significant inhibition of CMCs required stimulation frequencies of 10 Hz and greater. Phentolamine (3.6 μM) abolished effects of colonic nerve stimulation, consistent with a sympathetic noradrenergic mechanism. Sympathetic inhibition was constrained to regions with intact extrinsic nerve pathways, allowing normal motor behaviors to continue without modulation in adjacent extrinsically denervated regions of the same colonic segments. The results demonstrate differential sensitivities to sympathetic input among distinct neurogenic motor behaviors of the colon. Together with findings indicating CMCs activate colo‐colonic sympathetic reflexes through the IMG, these results raise the possibility that CMCs may paradoxically facilitate suppression of pellet movement in vivo, through peripheral sympathetic reflex circuits.

Mechanisms underlying initiation of propulsion in guinea pig distal colon

Publisher: American Physiological Society

Date: 08-2022

DOI: 10.1152/AJPGI.00055.2022

Abstract: The colonic motor complex (CMC) initiates propulsion in guinea pig colon. Here, CMCs evoked by an intraluminal pellet were restored during nicotinic receptor blockade by pharmacological agents that directly or indirectly enhance intrinsic primary afferent neuron (IPAN) excitability. IPANs are the only enteric neuron in colon that contain CGRP. Blocking CGRP receptors decreased CMC frequency, implicating their role in CMC initiation. The results support a role for IPANs in the initiation of CMCs.

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

Publisher: Wiley

Date: 2006

DOI: 10.1111/J.1365-2982.2005.00724.X

Abstract: 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.

Abnormal Perception of Urge to Defecate: An Important Pathophysiological Mechanism in Women With Chronic Constipation

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 15-04-2022

DOI: 10.14309/AJG.0000000000001794

Abstract: Although the association of absent or attenuated “call to stool” with constipation is well-recognized, no studies have systematically evaluated the perception of urge to defecate in a well-defined cohort of patients with chronic constipation (CC). A prospective study of 43 healthy adult women and 140 consecutive adult women attending a tertiary center for investigation of CC. All participants completed a 5-day viscerosensory questionnaire, and all women with CC also underwent anorectal physiologic investigations. Normal urge perception and abnormal urge perception were defined using a Naive Bayes model trained in healthy women (95% having normal urge). In total, 181 toilet visits in healthy women and 595 in women with CC were analyzed. Abnormal urge perception occurred in 70 (50.0%) women with CC. In this group, the urge to defecate was more often experienced as abdominal sensation (69.3% vs 41.4% P 0.0001), and the viscerosensory referral area was 81% larger (median pixels anterior: 1,849 vs 1,022 P 0.0001) compared to women with CC and normal urge perception. Abnormal (vs normal) urge in women with CC was associated with more severe constipation (Cleveland Clinic constipation score: 19 vs 15 P 0.0001), irritable bowel syndrome (45.7% vs 22.9% P 0.0001), and a functional evacuation disorder on defecography (31.3% vs 14.3% P = 0.023). A distinct pattern of abnormal urge was found in women with CC and rectal hyposensitivity. Abnormal urge perception was observed in 50% of women with CC and was frequently described as abdominal sensation, supporting the concept that sensory dysfunction makes an important contribution to the pathophysiology of constipation.

Abnormal predefecatory colonic motor patterns define constipation in obstructed defecation

Publisher: Elsevier BV

Date: 07-2004

DOI: 10.1053/J.GASTRO.2004.03.066

Abstract: The pathophysiology of constipation in the syndrome of obstructed defecation is unknown. Using 24-hour pancolonic manometric recordings of the unprepared colon to record basal pressures and spontaneous defecation episodes, we tested the hypothesis that the frequency, timing, or spatial distribution of propagating colonic pressure waves is abnormal in patients with obstructed defecation. In 11 patients with obstructed defecation and 16 healthy controls, pressures were recorded using a nasocolonic catheter that was positioned such that 16 recording sites spanned the unprepared colon at 7.5-cm intervals. The overall frequency of propagating sequences (PS) in the colon did not differ between patients and controls. When compared with controls, patients had a significant increase in the frequency of retrograde and antegrade PS (P < 0.05) in the left colon and a significant reduction in the litude of propagating pressure waves throughout the entire colon (P < 0.03). Defecation occurred in 6 of 11 patients and 9 of 16 controls. In the 15 minutes before defecation, controls showed a highly significant increase in frequency (P = 0.001) and litude (P = 0.01) of PS. In contrast, patients did not demonstrate this or the typical spatiotemporal organization of PS normally observed before expulsion of stool. Patients with obstructed defecation lack the normal predefecatory augmentation in frequency and litude of propagating pressure waves and lack the normal stereotypic spatiotemporal patterning of colonic pressure waves that would normally culminate in effective expulsion of stool.

Measurement of muscular activity associated with peristalsis in the human gut using fibre Bragg grating arrays

Publisher: Institute of Electrical and Electronics Engineers (IEEE)

Date: 2012

DOI: 10.1109/JSEN.2011.2123883

Closely spaced fibre bragg grating sensors for detailed measurement of peristalsis in the human gut

Publisher: SPIE

Date: 05-10-2009

DOI: 10.1117/12.833678

A composite fibre optic catheter for monitoring peristaltic transit of an intra-luminal bead

Publisher: Wiley

Date: 30-11-2016

DOI: 10.1002/JBIO.201500187

Abstract: A fibre optic motion sensor has been developed for monitoring the proximity and direction of motion of a ferrous bead travelling axial to the sensor. By integrating an array of these sensors into our previously developed fibre optic manometry catheters we demonstrate simultaneous detection of peristaltic muscular activity and the associated motion of ferrous beads through a colonic lumen. This allows the motion of solid content to be temporally and spatially related to pressure variations generated by peristaltic contractions without resorting to videoflouroscopy to track the motion of a radio opaque bolus. The composite catheter has been tested in an in-vitro animal preparation consisting of excised sections of rabbit colon. Cut-away image of the fibre optic motion sensor showing the location of the fibre Bragg gratings and the rare earth magnet.

Characterizing colonic motility in children with chronic intractable constipation: a look beyond high-amplitude propagating sequences

Publisher: Wiley

Date: 12-02-2016

DOI: 10.1111/NMO.12771

Abstract: Children with chronic intractable constipation experience severe and long-lasting symptoms, which respond poorly to conventional therapeutic strategies. Detailed characterization of colonic motor patterns in such children has not yet been obtained. In 18 children with chronic intractable constipation, a high-resolution water-perfused manometry catheter (36 sensors at 1.5-cm intervals) was colonoscopically placed with the tip at the distal transverse colon. Colonic motor patterns were recorded for 2 h prior to and after a meal and then after colonic infusion of bisacodyl. These data were compared with previously published colonic manometry data from 12 healthy adult controls and 14 adults with slow-transit constipation. The postprandial number of the retrograde cyclic propagating motor pattern was significantly reduced in these children compared with healthy adults (children, 3.1 ± 4.7/h vs healthy adults, 34.7 ± 45.8/h p < 0.0001) but not constipated adults (4.5 ± 5.6/h p = 0.9). The number of preprandial long-single motor patterns was significantly higher (p = 0.003) in children (8.0 ± 13.2/h) than in healthy adults (0.4 ± 0.9/h) and in constipated adults (0.4 ± 0.7/h). Postprandial high- litude propagating sequences (HAPSs) were rarely observed in children (2/18), but HAPS could be induced by bisacodyl in 16 of 18 children. Children with chronic intractable constipation show a similar impaired postprandial colonic response to that seen in adults with slow-transit constipation. Children may have attenuated extrinsic parasympathetic inputs to the colon associated with an increased incidence of spontaneous long-single motor patterns.

Identification of neurogenic intestinal motility patterns in silver perch ( Bidyanus bidyanus ) that persist over wide temperature ranges

Publisher: Wiley

Date: 19-12-2021

DOI: 10.1111/NMO.14037

Abstract: Fish are increasingly being utilized as a model species for genetic manipulation studies related to gastrointestinal (GI) motility. Our aim was to identify whether patterns of GI motility in fish and the mechanisms underlying their generation are similar to those recorded from mammals (including humans). The entire intestine was removed from euthanized adult Silver Perch (n = 11) and lesioned at the midway point to obtain two equal lengths. Proximal and distal segments were studied separately in organ baths with oxygenated Krebs solution, maintained at either 15°C (n = 5) or 25°C (n = 6). Motility was analyzed during rest, after oral infusion of Krebs solution, and after application of hexamethonium (100 µM) and tetrodotoxin (TTX) (0.6 µM). Antegrade and retrograde propagating contractions (PC) were recorded in all preparations. In the proximal intestine, at 15 and 25°C, retrograde PCs occurred at 2.7 [1.7-4.5] and 3.1 [1.6-6.5] times the frequency of antegrade PCs, respectively. Colder temperatures did not inhibit PC frequency. Hexamethonium did not inhibit PC, and however, TTX abolished all contractile activity. Both neurogenic antegrade and retrograde propagating contractions occur throughout the intestine of Silver Perch. However, unlike the mammalian colon, these motor patterns do not require enteric nicotinic transmission and they are not inhibited by cold temperatures (15°C). Therefore, while the GI motility patterns in Silver Perch resemble those recorded from the colon of mammals, there may be differences in the mechanisms that underlying their generation.

New concepts in the pathophysiology of fecal incontinence

Publisher: AME Publishing Company

Date: 04-2022

DOI: 10.21037/ALES-2022-02

Post‐operative anorectal manometry in children with Hirschsprung disease: A systematic review

Publisher: Wiley

Date: 29-12-2021

DOI: 10.1111/NMO.14311

Abstract: Hirschsprung disease is commonly encountered by pediatric surgeons. Despite advances in the surgical management, these children may experience symptoms of bowel dysfunction throughout adulthood. Anorectal manometry may be used to assess post‐operative anorectal structure and function. This review aimed to consolidate and evaluate the literature pertaining to post‐operative findings of anorectal manometry in children with Hirschsprung disease. (1) Synthesize the available data regarding anorectal motility patterns in children following repair of Hirschsprung disease. (2) Evaluate the reported anorectal manometry protocols. We performed a systematic review of four databases: Embase, MEDLINE, the Cochrane Library, and PubMed. This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA). Studies reporting results of post‐operative anorectal manometry in children with Hirschsprung disease were evaluated for inclusion. Twenty‐three studies satisfied inclusion criteria, with a combined cohort of 939 patients. Post‐operative anorectal manometry results were reported for 682 children. The majority of included studies were assessed as “poor quality.” Disparate manometry protocols, heterogeneous cohorts, and lack of standardized outcome assessments introduced a risk of outcome reporting bias, limited the comparability of results, and impeded clinical translation of findings. This systematic review demonstrated the lack of high‐quality evidence underlying the current understanding of post‐operative anorectal motility in children with HD. There was little consistency in reported manometry outcomes between studies. In future work, emphasis must be placed on the application of standardized manometry protocols, cohort reporting, and patient outcome assessments.

Understanding the physiology of human defaecation and disorders of continence and evacuation

Publisher: Springer Science and Business Media LLC

Date: 09-08-2021

DOI: 10.1038/S41575-021-00487-5

Recording In Vivo Human Colonic Motility: What Have We Learnt Over the Past 100 Years?

Publisher: Springer International Publishing

Date: 2016

DOI: 10.1007/978-3-319-27592-5_20

Abstract: To understand the abnormalities that underpin functional gut disorders we must first gain insight into the normal patterns of gut motility. While detailed information continually builds on the motor patterns (and mechanisms that control them) of the human esophagus and anorectum, our knowledge of normal and abnormal motility in the more inaccessible regions of the gut remains poor. This particularly true of the human colon. Investigation of in vivo colonic motor patterns is achieved through measures of transit (radiology, scintigraphy and, more recently, "smart pills") or by direct real-time recording of colonic contractility (intraluminal manometry). This short review will provide an overview of findings from the past and present and attempt to piece together the complex nature of colonic motor patterns. In doing so it will build a profile of human colonic motility and determine the likely mechanisms that control this motility.

Technical advances in monitoring human motility patterns

Publisher: Wiley

Date: 04-2010

DOI: 10.1111/J.1365-2982.2010.01488.X

Abstract: Abnormal motor patterns are implicated in many motility disorders. However, for many regions of the gut, our knowledge of normal and abnormal motility behaviors and mechanisms remains incomplete. There have been many recent advances in the development of techniques to increase our knowledge of gastrointestinal motility, some readily available while others remain confined to research centers. This review highlights a range of these recent developments and examines their potential to help diagnose and guide treatment for motility disorders.

International Consensus Definition of Low Anterior Resection Syndrome

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 03-2020

DOI: 10.1097/DCR.0000000000001583

Abstract: Low anterior resection syndrome is pragmatically defined as disordered bowel function after rectal resection leading to a detriment in quality of life. This broad characterization does not allow for precise estimates of prevalence. The low anterior resection syndrome score was designed as a simple tool for clinical evaluation of low anterior resection syndrome. Although the low anterior resection syndrome score has good clinical utility, it may not capture all important aspects that patients may experience. The aim of this collaboration was to develop an international consensus definition of low anterior resection syndrome that encompasses all aspects of the condition and is informed by all stakeholders. This international patient-provider initiative used an online Delphi survey, regional patient consultation meetings, and an international consensus meeting. Three expert groups participated: patients, surgeons, and other health professionals from 5 regions (Australasia, Denmark, Spain, Great Britain and Ireland, and North America) and in 3 languages (English, Spanish, and Danish). The primary outcome measured was the priorities for the definition of low anterior resection syndrome. Three hundred twenty-five participants (156 patients) registered. The response rates for successive rounds of the Delphi survey were 86%, 96%, and 99%. Eighteen priorities emerged from the Delphi survey. Patient consultation and consensus meetings refined these priorities to 8 symptoms and 8 consequences that capture essential aspects of the syndrome. S ling bias may have been present, in particular, in the patient panel because social media was used extensively in recruitment. There was also dominance of the surgical panel at the final consensus meeting despite attempts to mitigate this. This is the first definition of low anterior resection syndrome developed with direct input from a large international patient panel. The involvement of patients in all phases has ensured that the definition presented encompasses the vital aspects of the patient experience of low anterior resection syndrome. The novel separation of symptoms and consequences may enable greater sensitivity to detect changes in low anterior resection syndrome over time and with intervention.

Colonic dysmotility in constipation

Publisher: Elsevier BV

Date: 02-2011

DOI: 10.1016/J.BPG.2010.12.006

Abstract: Constipation is a common and distressing condition with major morbidity, health care burden, and impact on quality of life. Colonic motor dysfunction remains the leading hypothesis to explain symptom generation in the most severe cases of chronic constipation and physiological testing plays a role in identifying the colonic dysmotility and the subsequent patient management. Measurement of colonic motor patterns and transit has enhanced our knowledge of normal and abnormal colonic motor physiology. The scope of this review encompasses the latest findings that improve our understanding of the motility disorders associated with colonic dysfunction in both the paediatric and adult population suffering from constipation.

Sacral nerve stimulation induces pan-colonic propagating pressure waves and increases defaecation frequency in patients with slow transit constipation

Publisher: Wiley

Date: 13-11-2007

DOI: 10.1111/J.1463-1318.2006.01096.X

Abstract: Colonic propagating sequences are important for normal colonic transit and defecation. The frequency of these motor patterns is reduced in slow-transit constipation. Sacral nerve stimulation (SNS) is a useful treatment for fecal and urinary incontinence. A high proportion of these patients have also reported altered bowel function. The effects of SNS on colonic propagating sequences in constipation are unknown. Our aims were to evaluate the effect of SNS on colonic pressure patterns and evaluate its therapeutic potential in severe constipation. In eight patients with scintigraphically confirmed slow-transit constipation, a manometry catheter (16 recording sites at 7.5 cm intervals) was positioned colonoscopically and the tip fixed in the caecum. Temporary electrodes (Medtronic) were implanted in the S2 and S3 sacral nerve foramina under general anaesthesia. In the fasted state, 14 Hz stimulation was administered and four sets of parameters (pulse width 300 or 400 micros S2 and S3) were tested in four 2-h epochs, in random order, over 2 days. Patients were then discharged home with the sacral wires in situ and a 3-week trial stimulation commenced during which patients completed a daily stool diary. When compared with basal activity, electrical stimulation to S3 significantly increased pan-colonic antegrade propagating sequence (PS) frequency (5.4 +/- 4.2 vs 11.3 +/- 6.6 PS/h P=0.01). Stimulation at S2 significantly increased retrograde PSs (basal 2.6 +/- 1.8 vs SNS 5.6 +/- 4.8 PS/h P=0.03). During the subsequent three-week trial (continuous stimulation), six of eight reported increased bowel frequency with a reduction in laxative usage. These data demonstrate that SNS induces pan-colonic propagating pressure waves and therefore shows promise as a potential therapy for severe refractory constipation.

Characterisation of parasympathetic ascending nerves in human colon

Publisher: Frontiers Media SA

Date: 12-2022

DOI: 10.3389/FNINS.2022.1072002

Abstract: In the human large bowel, sacral parasympathetic nerves arise from S2 to S4, project to the pelvic plexus (“hypogastric plexus”) and have post-ganglionic axons entering the large bowel near the rectosigmoid junction. They then run long distances orally or aborally within the bowel wall forming “ascending nerves” or “shunt fascicles” running in the plane of the myenteric plexus. They form bundles of nerve fibres that can be distinguished from the myenteric plexus by their straight orientation, tendency not to merge with myenteric ganglia and greater width. To identify reliable marker(s) to distinguish these bundles of ascending nerves from other extrinsic and intrinsic nerves in human colon. Human colonic segments were obtained with informed consent, from adult patients undergoing elective surgery ( n = 21). Multi-layer immunohistochemical labelling with neurofilament-H (NF200), myelin basic protein (MBP), von Willebrand factor (vWF), and glucose transporter 1 (GLUT1), and rapid anterograde tracing with biotinamide, were used to compare ascending nerves and lumbar colonic nerves. The rectosigmoid and rectal specimens had 6–11 ascending nerves spaced around their circumference. Distal colon specimens typically had 1–3 ascending nerves, with one located near the mesenteric taenia coli. No ascending nerves were observed in ascending colon specimens. GLUT1 antisera labelled both sympathetic lumbar colonic nerves and ascending nerves in the gut wall. Lumbar colonic nerves joined the myenteric plexus and quickly lost GLUT1 labelling, whereas GLUT1 staining labelled parasympathetic ascending nerves over many centimetres. Ascending nerves can be distinguished in the colorectum of humans using GLUT1 labelling combined with NF200.

Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON): study protocol for a randomised controlled trial

Publisher: Springer Science and Business Media LLC

Date: 20-08-2019

DOI: 10.1186/S13063-019-3562-6

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

Publisher: Wiley

Date: 24-02-2010

DOI: 10.1111/J.1365-2982.2010.01480.X

Abstract: 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. 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. 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 litude 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. 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.

Impaired proximal colonic motor response to rectal mechanical and chemical stimulation in Obstructed Defecation

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 09-2005

DOI: 10.1007/S10350-005-0087-8

Abstract: Both motor and sensory dysfunction have been implicated in the pathogenesis of obstructed defecation. We have found that despite preservation of a defecatory urge, patients with obstructed defecation have lost the normal predefecatory augmentation in frequency and litude of colonic propagating pressure waves. This observation might be explainable by either altered rectal sensory thresholds or by dysfunction in the colonic motor apparatus. By measuring rectal sensory thresholds and proximal colonic motor responses to rectal mechanical and chemical stimuli, we tested the hypotheses that central perception of rectal stimuli is enhanced and that the proximal colonic motor response to rectal stimulation is attenuated. In seven patients with obstructed defecation and ten healthy volunteers we measured proximal colonic motor responses and sensory thresholds in response to both rectal balloon distention and rectal instillation of chenodeoxycholic acid. In controls, but not in patients, rectal mechanical distention significantly reduced and chemical stimulation significantly increased the frequency of proximal colonic propagating sequences (P = 0.01). There was no significant difference in rectal sensory thresholds between patients and controls. Prior instillation of chenodeoxycholic acid significantly reduced (P < 0.03) maximum tolerated balloon volume and defecatory urge volume to comparable degree in both patients and controls. In obstructed defecation, 1) the normal rectocolonic pathways mediating stimulation-induced proximal colonic propagating pressure waves are nonfunctioning, and. 2) central perception of these rectal stimuli is normal.

First translational consensus on terminology and definitions of colonic motility in animals and humans studied by manometric and other techniques

Publisher: Springer Science and Business Media LLC

Date: 11-07-2019

DOI: 10.1038/S41575-019-0167-1

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

Publisher: Wiley

Date: 06-09-2010

DOI: 10.1111/J.1365-2982.2010.01597.X

Abstract: 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. 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. Pan-colonic, 24 h, spatiotemporal mapping identified for the first time in STC patients: a marked paucity of propagating pressure waves in the midcolon (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. Pancolonic, 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.

Neural motor complexes propagate continuously along the full length of mouse small intestine and colon

Publisher: American Physiological Society

Date: 2019

DOI: 10.1152/AJPGI.00185.2019

Abstract: Cyclical propagating waves of muscle contraction have been recorded in isolated small intestine or colon, referred to here as motor complexes (MCs). Small intestinal and colonic MCs are neurogenic, occur at similar frequencies, and propagate orally or aborally. Whether they can be coordinated between the different gut regions is unclear. Motor behavior of whole length mouse intestines, from duodenum to terminal rectum, was recorded by intraluminal multisensor catheter. Small intestinal MCs were recorded in 27/30 preparations, and colonic MCs were recorded in all preparations ( n = 30) with similar frequencies (0.54 ± 0.03 and 0.58 ± 0.02 counts/min, respectively). MCs propagated across the ileo-colonic junction in 10/30 preparations, forming “full intestine” MCs. The cholinesterase inhibitor physostigmine increased the probability of a full intestine MC but had no significant effect on frequency, speed, or direction. Nitric oxide synthesis blockade by N ω -nitro-l-arginine, after physostigmine, increased MC frequency in small intestine only. Hyoscine-resistant MCs were recorded in the colon but not small intestine ( n = 5). All MCs were abolished by hexamethonium ( n = 18) or tetrodotoxin ( n = 2). The enteric neural mechanism required for motor complexes is present along the full length of both the small and large intestine. In some cases, colonic MCs can be initiated in the distal colon and propagate through the ileo-colonic junction, all the way to duodenum. In conclusion, the ileo-colonic junction provides functional neural continuity for propagating motor activity that originates in the small or large intestine. NEW & NOTEWORTHY Intraluminal manometric recordings revealed motor complexes can propagate antegradely or retrogradely across the ileo-colonic junction, spanning the entire small and large intestines. The fundamental enteric neural mechanism(s) underlying cyclic motor complexes exists throughout the length of the small and large intestine.

Intraluminal impedance detects failure of pharyngeal bolus clearance during swallowing: a validation study in adults with dysphagia

Publisher: Wiley

Date: 03-2009

DOI: 10.1111/J.1365-2982.2008.01180.X

Abstract: Multichannel intraluminal impedance (MII) detects bolus flow through a healthy pharynx. The aim of this study was to determine whether the technique detects bolus flow and retention in patients with pharyngeal dysphagia develop appropriate impedance-based criteria for assessing patients and to provide some preliminary insights into the clinical utility of the technique. Pharyngo-oesophageal pressure and impedance were recorded simultaneously with videofluoroscopy (VF) during swallows in six patients with dysphagia. Agreement, as to the presence or absence of bolus material, between the VF and MII was expressed using the Cohen's Kappa statistic. To test whether the impedance criteria for the detection of bolus passage in dysphagia could be improved, a Kappa statistic was calculated in an iterative process for a range of impedance values (100%-0%) defining bolus head entry and bolus tail clearance from the pharynx. Bolus presence according to the MII criteria previously derived by us in healthy controls demonstrated a modest correlation with VF when applied to this dysphagia population [0.37, 0.5 and 0.58 in the hypopharynx, upper oesophageal sphincter (UOS) and proximal oesophagus respectively]. In the patient population, the optimal impedance criteria were 50% for bolus head entry and 20% for bolus tail clearance. Adopting these criteria demonstrated enhanced agreement between VF and impedance yielding Kappa coefficients of 0.42 in the hypopharynx, 0.54 in the UOS and 0.62 in the proximal oesophagus. With the adoption of appropriate criteria, pharyngeal impedance measurement can accurately detect bolus passage and failed or impaired clearance during swallowing in patients with dysphagia.

Quantification of in vivo colonic motor patterns in healthy humans before and after a meal revealed by high-resolution fiber-optic manometry

Publisher: Wiley

Date: 11-08-2014

DOI: 10.1111/NMO.12408

Temporal relationships between wall motion, intraluminal pressure, and flow in the isolated rabbit small intestine

Publisher: American Physiological Society

Date: 04-2011

DOI: 10.1152/AJPGI.00532.2010

Abstract: Intraluminal manometry is a tool commonly used to record motility in the human digestive tract. The recorded signal results from a combination of factors, including the hydrodynamic pressure transmitted through the intestinal contents due to contraction of the gut wall and the force of the gut wall acting on the sensors in regions of a luminal occlusion. However, the actual relationships between small bowel wall contraction, the measured intraluminal pressure, and the resultant flow have not been directly addressed. Video recording and high-resolution fiber-optic manometry were used to create spatiotemporal video maps of diameter and intraluminal pressure from isolated segments of rabbit small intestine. In the unstimulated gut, longitudinal muscle contractions were the only detectable motor pattern circular muscle contractions were elicited by distension or erythromycin (1 μM). Longitudinal muscle contractions were not lumen-occlusive, although they caused measurable low- litude changes in pressure. Localized nonpropagating circular muscle contractions caused small localized, nonpropagating peaks of intraluminal pressure. Propagating contractions of circular muscle evoked larger, propagating pressure changes that were associated with outflow. Propagating circular muscle contractions often caused dilation of aboral receiving segments, corresponding to “common cavities” these were propulsive, despite their low intraluminal pressure. The highest- litude pressure events were caused by lumen-occlusive circular muscle contractions that squeezed directly against the catheter. These data allow us to define the complex relationships between wall motion, intraluminal pressure, and flow. A strong correlation between circular and longitudinal muscle contraction and intraluminal pressure was demonstrated. Common-cavity pressure events, caused by propulsion of content by circular muscle contractions into a receptive segment, were often of low litude but were highly propulsive. Studies of wall motion in isolated preparations, combined with manometry, can assist in interpretation of pressure recordings in vivo.

Ascending excitatory neural pathways modulate slow phasic myogenic contractions in the isolated human colon

Publisher: Wiley

Date: 05-2013

DOI: 10.1111/NMO.12129

Abstract: In animal models, enteric reflex pathways have potent effects on motor activity their roles have been much less extensively studied in human gut. The aim of this study was to determine if ascending excitatory interneuronal pathways can modulate spontaneous phasic contractions in isolated preparations of human colonic circular muscle. Human colonic preparations were cut into T shapes, with vertical bar of the 'T' pharmacologically isolated. Electrical stimulation and the nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), were applied to the isolated region and circular muscle contractile activity was measured from the cross-bar of the T, more than 10 mm orally from the region of stimulation. The predominant form of spontaneous muscle activity consisted of tetrodotoxin-resistant, large litude, slow phasic contractions (SPCs), occurring at average intervals of 124 ± 68 s. Addition of a high concentration of hexamethonium (1 mmol L(-1)) to the superfusing solution significantly increased the interval between SPCs to 278.1 ± 138.3 s (P < 0.005). Focal electrical stimulation more than 10 mm aboral to the muscle recording site advanced the onset of the next SPC, and this effect persisted in hexamethonium. However, the effect of electrical stimulation was blocked by tetrodotoxin (TTX, 1 μmol L(-1)). Application of the nicotinic agonist DMPP (1 mmol L(-1)) to the aboral chamber often stimulated a premature SPC (n = 4). The major form of spontaneous contractility in preparations of human colonic circular muscle is SPCs, which are myogenic in origin. Activation of ascending excitatory neural pathways, which involve nicotinic receptors, can modulate the timing of SPCs and thus influence human colonic motility.

Neuromechanical factors involved in the formation and propulsion of fecal pellets in the guinea-pig colon.

Publisher: Wiley

Date: 06-08-2015

DOI: 10.1111/NMO.12646

Abstract: The neuromechanical processes involved in the formation and propulsion of fecal pellets remain incompletely understood. We analyzed motor patterns in isolated segments of the guinea-pig proximal and distal colon, using video imaging, during oral infusion of liquid, viscous material, or solid pellets. Colonic migrating motor complexes (CMMCs) in the proximal colon ided liquid or natural semisolid contents into elongated shallow boluses. At the colonic flexure these boluses were formed into shorter, pellet-shaped boluses. In the non-distended distal colon, spontaneous CMMCs produced small dilations. Both high- and low-viscosity infusions evoked a distinct motor pattern that produced pellet-shaped boluses. These were propelled at speeds proportional to their surface area. Solid pellets were propelled at a speed that increased with diameter, to a maximum that matched the diameter of natural pellets. Pellet speed was reduced by increasing resistive load. Tetrodotoxin blocked all propulsion. Hexamethonium blocked normal motor patterns, leaving irregular propagating contractions, indicating the existence of neural pathways that did not require nicotinic transmission. Colonic migrating motor complexes are responsible for the slow propulsion of the soft fecal content in the proximal colon, while the formation of pellets at the colonic flexure involves a content-dependent mechanism in combination with content-independent spontaneous CMMCs. Bolus size and consistency affects propulsion speed suggesting that propulsion is not a simple reflex but rather a more complex process involving an adaptable neuromechanical loop.

Simultaneous Colonic Pressure Waves in Children and Young Adults with Gastrointestinal Motility Disorders: Artefact or Colonic Physiology?

Publisher: MDPI AG

Date: 06-09-2023

DOI: 10.3390/JCM12185808

Characterization of the colonic response to bisacodyl in children with treatment‐refractory constipation

Publisher: Wiley

Date: 13-04-2020

DOI: 10.1111/NMO.13851

Altered colonic motility is associated with low anterior resection syndrome

Publisher: Wiley

Date: 14-12-2020

DOI: 10.1111/CODI.15465

High-resolution colonic motility recordings in vivo compared with ex vivo recordings after colectomy, in patients with slow transit constipation

Publisher: Wiley

Date: 09-06-2016

DOI: 10.1111/NMO.12884

Abstract: The pathogenesis of slow transit constipation (STC) remains poorly understood, with intrinsic and extrinsic abnormalities implicated. Here, we present high-resolution colonic manometry recordings from four STC patients recorded before total colectomy, and subsequently, ex vivo, after excision. In four female, treatment-resistant STC patients (median age 35.5 years), a fiber-optic manometry catheter (72 sensors spaced at 1 cm intervals) was placed with the aid of a colonoscope, to the mid-transverse colon. Colonic manometry was recorded 2 h before and after a meal. After the colectomy, ex vivo colonic manometry was recorded in an organ bath. Ex vivo recordings were also made from colons from 4 patients (2 male median age 67.5 years) undergoing anterior resection for nonobstructive carcinoma ('control' tissue). A large increase in 'short single propagating contractions' was recorded in STC colon ex vivo compared to in vivo (ex vivo 61.3 ± 32.7 vs in vivo 2.5 ± 5/h). In STC patients, in vivo, the dominant frequency of contractile activity was 2-3 cycle per minute (cpm), whereas 1-cpm short-single propagating contractions dominated ex vivo. This same 1-cpm frequency was also dominant in control colons ex vivo. In comparison to control adults, the colon of STC patients demonstrates significantly less propagating motor activity. However, once the STC colon is excised from the body it demonstrates a regular and similar frequency of propagating activity to control tissue. This paper provides interesting insights into the control of colonic motor patterns.

Esophageal neuromechanical states during solid bolus perception in healthy volunteers

Publisher: Wiley

Date: 08-2016

DOI: 10.1111/NMO.12881

Roles of three distinct neurogenic motor patterns during pellet propulsion in guinea-pig distal colon

Publisher: Wiley

Date: 10-2019

DOI: 10.1113/JP278284

Altered anal slow‐wave pressure activity in low anterior resection syndrome: short case series in two independent specialist centres provide new mechanistic insights

Publisher: Wiley

Date: 03-01-2021

DOI: 10.1111/CODI.15502

Diversity of neurogenic smooth muscle electrical rhythmicity in mouse proximal colon

Publisher: American Physiological Society

Date: 02-2019

DOI: 10.1152/AJPGI.00317.2019

Abstract: The mechanisms underlying electrical rhythmicity in smooth muscle of the proximal colon are incompletely understood. Our aim was to identify patterns of electrical rhythmicity in smooth muscle of the proximal region of isolated whole mouse colon and characterize their mechanisms of origin. Two independent extracellular recording electrodes were used to record the patterns of electrical activity in smooth muscle of the proximal region of whole isolated mouse colon. Cross-correlation analysis was used to quantify spatial coordination of these electrical activities over increasing electrode separation distances. Four distinct neurogenic patterns of electrical rhythmicity were identified in smooth muscle of the proximal colon, three of which have not been identified and consisted of bursts of rhythmic action potentials at 1–2 Hz that were abolished by hexamethonium. These neurogenic patterns of electrical rhythmicity in smooth muscle were spatially and temporally synchronized over large separation distances (≥2 mm rosto-caudal axis). Myogenic slow waves could be recorded from the same preparations, but they showed poor spatial and temporal coordination over even short distances (≤1 mm rostro-caudal axis). It is not commonly thought that electrical rhythmicity in gastrointestinal smooth muscle is dependent upon the enteric nervous system. Here, we identified neurogenic patterns of electrical rhythmicity in smooth muscle of the proximal region of isolated mouse colon, which are dependent on synaptic transmission in the enteric nervous system. If the whole colon is studied in vitro, recordings can preserve novel neurogenic patterns of electrical rhythmicity in smooth muscle. NEW & NOTEWORTHY Previously, it has not often been thought that electrical rhythmicity in smooth muscle of the gastrointestinal tract is dependent upon the enteric nervous system. We identified patterns of electrical rhythmicity in smooth muscle of the mouse proximal colon that were abolished by hexamethonium and involved the temporal synchronization of smooth muscle membrane potential over large spatial fields. We reveal different patterns of electrical rhythmicity in colonic smooth muscle that are dependent on the ENS.

Ensuring appropriate and proportionate responses to environmental threats: A response to Caras and Pasternak

Publisher: Elsevier BV

Date: 11-2010

DOI: 10.1016/J.OCECOAMAN.2010.10.003

Hyperactive cyclic motor activity in the distal colon after colonic surgery as defined by high-resolution colonic manometry.

Publisher: Oxford University Press (OUP)

Date: 14-04-2018

DOI: 10.1002/BJS.10808

Abstract: Recovery after colonic surgery is invariably delayed by disturbed gut motility. It is commonly assumed that colonic motility becomes quiescent after surgery, but this hypothesis has not been evaluated rigorously. This study quantified colonic motility through the early postoperative period using high-resolution colonic manometry. Fibre-optic colonic manometry was performed continuously before, during and after surgery in the left colon and rectum of patients undergoing right hemicolectomy, and in healthy controls. Motor events were characterized by pattern, frequency, direction, velocity, litude and distance propagated. Eight patients undergoing hemicolectomy and nine healthy controls were included in the study. Colonic motility became markedly hyperactive in all operated patients, consistently dominated by cyclic motor patterns. Onset of cyclic motor patterns began to a minor extent before operation, occurring with increasing intensity nearer the time of surgery the mean(s.d.) active duration was 12(7) per cent over 3 h before operation and 43(17) per cent within 1 h before surgery (P = 0.024) in fasted controls it was 2(4) per cent (P & 0·001). After surgery, cyclic motor patterns increased markedly in extent and intensity, becoming nearly continuous (active duration 94(13) per cent P & 0·001), with peak frequency 2–4 cycles per min in the sigmoid colon. This postoperative cyclic pattern was substantially more prominent than in non-operative controls, including in the fed state (active duration 27(20) per cent P & 0·001), and also showed higher antegrade velocity (P & 0·001). Distal gut motility becomes markedly hyperactive with colonic surgery, dominated by cyclic motor patterns. This hyperactivity likely represents a novel pathophysiological aspect of the surgical stress response. Hyperactive motility may contribute to gut dysfunction after surgery, potentially offering a new therapeutic target to enhance recovery.

Placebo Response Rates in Electrical Nerve Stimulation Trials for Fecal Incontinence and Constipation: A Systematic Review and Meta-Analysis

Publisher: Elsevier BV

Date: 12-2020

DOI: 10.1111/NER.13092

Paediatric and adult colonic manometry: A tool to help unravel the pathophysiology of constipation

Publisher: Baishideng Publishing Group Inc.

Date: 2010

DOI: 10.3748/WJG.V16.I41.5162

Identification of a Rhythmic Firing Pattern in the Enteric Nervous System That Generates Rhythmic Electrical Activity in Smooth Muscle

Publisher: Society for Neuroscience

Date: 28-05-2018

DOI: 10.1523/JNEUROSCI.3489-17.2018

A Fibre Bragg grating manometry catheter for in-vivo diagnostics of swallowing disorders

Publisher: IEEE

Date: 07-2008

DOI: 10.1109/OECCACOFT.2008.4610536

A research process for integrating Indigenous and scientific knowledge in cultural landscapes: principles and determinants of success in the Wet Tropics World Heritage Area, Australia

Publisher: Wiley

Date: 11-2011

DOI: 10.1111/J.1475-4959.2011.00451.X

Flinders Medical Centre

Location: Australia

View Organisation

Flinders University

Location: Australia

View Organisation

University Of New South Wales

Location: Australia

View Organisation

Flinders University

Location: No location found

View Organisation

Development Of Diagnostic Tools To Characterise Predictors Of Therapeutic Outcome In Severe Constipation

Start Date: 2010

End Date: 2013

Funder: National Health and Medical Research Council

How Stimulant Laxatives Work

Start Date: 2018

End Date: 2020

Funder: National Health and Medical Research Council

Colonic Dysmotility Is A Significant Aetiological Factor In Faecal Incontinence

Start Date: 2019

End Date: 2021

Funder: National Health and Medical Research Council

Defining The Colonic Abnormality Underlying Severe Constipation And Evaluating The Efficacy Of A Novel Treatment Therapy

Start Date: 2007

End Date: 2009

Funder: National Health and Medical Research Council

The Causes Of Constipation. Reclassifying Constipation Using MRI And High Resolution Manometry To Define Mechanism Of Disease And Target Treatment.

Start Date: 2016

End Date: 2019

Funder: Medical Research Council

Unified Framework Of Intestinal Motility

Start Date: 2012

End Date: 2014

Funder: Australian Research Council

Comprehensive Structural And Functional Mapping Of Mammalian Colonic Nervous System

Start Date: 2017

End Date: 2020

Funder: Office of the Director

Cellular Bases Of Enteric Neural Circuitry Underlying Gut Propulsion

Start Date: 2019

End Date: 2021

Funder: Australian Research Council

How Intestinal Motility Activates Sensory Pathways

Start Date: 2013

End Date: 2015

Funder: National Health and Medical Research Council

Mechanical Factors In Normal Human Colonic Motility

Start Date: 2014

End Date: 2016

Funder: National Health and Medical Research Council

Development Of A Nociceptive Measuring Device Capable Of Differentiating Chronic Pain States

Start Date: 2022

End Date: 2026

Funder: National Health and Medical Research Council

A Multi-site Randomised Controlled Trial Comparing The Severity Of Constipation Symptoms Experienced By Palliative Care Patients Receiving Usual Care Compared To Those Diagnosed And Managed According To The Underlying Pathophysiology.

Start Date: 2011

End Date: 2015

Funder: National Health and Medical Research Council

Discovery Projects - Grant ID: DP120102192

Start Date: 2012

End Date: 12-2015

Amount: $310,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP190103628

Start Date: 06-2019

End Date: 05-2023

Amount: $453,000.00

Funder: Australian Research Council