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Article ; Online: A new understanding of the physiology and pathophysiology of colonic motility?

Dinning, P G

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society

2018 Volume 30, Issue 11, Page(s) e13395

Abstract: Background: In recent years, high-resolution manometry has been used in an attempt to gain a greater insight into the physiology/pathophysiology of colonic contractile activity in healthy adults and patients with colonic motility disorders. New colonic ... ...

Abstract	Background: In recent years, high-resolution manometry has been used in an attempt to gain a greater insight into the physiology/pathophysiology 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. Purpose: 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.
MeSH term(s)	Colon/physiology ; Colonic Diseases/physiopathology ; Gastrointestinal Motility/physiology ; Humans ; Manometry/methods
Language	English
Publishing date	2018-07-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1186328-6
ISSN	1365-2982 ; 1350-1925
ISSN (online)	1365-2982
ISSN	1350-1925
DOI	10.1111/nmo.13395
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Article: Antibody elution with 2-me/SDS solution: Uses for multi-layer immunohistochemical analysis of wholemount preparations of human colonic myenteric plexus.

Humenick, Adam / Johnson, M E / Chen, B N / Wee, M / Wattchow, D A / Costa, M / Dinning, P G / Brookes, S J H

Heliyon

2024 Volume 10, Issue 5, Page(s) e26522

Abstract: Indirect immunofluorescence is usually restricted to 3-5 markers per preparation, limiting analysis of coexistence. A solution containing 2-mercaptoethanol and sodium dodecyl sulfate (2-ME/SDS) can elute indirect immunofluorescence labelling (i.e. ... ...

Abstract	Indirect immunofluorescence is usually restricted to 3-5 markers per preparation, limiting analysis of coexistence. A solution containing 2-mercaptoethanol and sodium dodecyl sulfate (2-ME/SDS) can elute indirect immunofluorescence labelling (i.e. primary antisera followed by fluorophore-conjugated secondary antisera) and has been used for sequential staining of sections. The aim of this study was to test whether 2-ME/SDS is effective for eluting indirect immunofluorescent staining (with primary antisera visualised by fluorophore-coupled secondary antisera) in wholemount preparations. We also analysed how 2-ME/SDS may work and used this understanding to devise additional uses for immunofluorescence in the nervous system. 2-ME/SDS appears to denature unfixed proteins (including antisera used as reagents) but has much less effect on antigenicity of formaldehyde-fixed epitopes. Moieties linked by strong biotin-streptavidin bonds are highly resistant to elution by 2-ME/SDS. Two primary antisera raised in the same species can be applied without spurious cross-reactivity, if a specific order of labelling is followed. The first primary antiserum is followed by a biotinylated secondary, then a tertiary of fluorophore-conjugated streptavidin. The preparation is then exposed to 2-ME/SDS, which has minimal impact on labelling by the first primary/secondary/tertiary combination. However, when this is followed by a second primary antiserum (raised in the same species), followed by a fluorophore-conjugated secondary antiserum, the intervening 2-ME/SDS exposure prevents cross-reactivity between primary and secondary antisera of the two layers. A third property of 2-ME/SDS is that it reduces lipofuscin autofluorescence, although it also raises background fluorescence and strongly enhances autofluorescence of erythrocytes. In summary, 2-ME/SDS is easy to use, cost-effective and does not require modified primary antisera. It can be used as the basis of a multi-layer immunohistochemistry protocol and allows 2 primary antisera raised in the same species to be used together.
Language	English
Publishing date	2024-02-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2024.e26522
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Article ; Online: 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).

Dinning, P G

The British journal of surgery

2013 Volume 100, Issue 10, Page(s) 1396–1397

MeSH term(s)	Electric Stimulation Therapy/methods ; Fecal Incontinence/therapy ; Female ; Humans ; Male
Language	English
Publishing date	2013-09
Publishing country	England
Document type	Comment ; Letter
ZDB-ID	2985-3
ISSN	1365-2168 ; 0263-1202 ; 0007-1323 ; 1355-7688
ISSN (online)	1365-2168
ISSN	0263-1202 ; 0007-1323 ; 1355-7688
DOI	10.1002/bjs.9245
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Article: Circadian rhythms in colonic function.

Hibberd, Timothy J / Ramsay, Stewart / Spencer-Merris, Phaedra / Dinning, Phil G / Zagorodnyuk, Vladimir P / Spencer, Nick J

Frontiers in physiology

2023 Volume 14, Page(s) 1239278

Abstract: A rhythmic expression of clock genes occurs within the cells of multiple organs and tissues throughout the body, termed "peripheral clocks." Peripheral clocks are subject to entrainment by a multitude of factors, many of which are directly or indirectly ... ...

Abstract	A rhythmic expression of clock genes occurs within the cells of multiple organs and tissues throughout the body, termed "peripheral clocks." Peripheral clocks are subject to entrainment by a multitude of factors, many of which are directly or indirectly controlled by the light-entrainable clock located in the suprachiasmatic nucleus of the hypothalamus. Peripheral clocks occur in the gastrointestinal tract, notably the epithelia whose functions include regulation of absorption, permeability, and secretion of hormones; and in the myenteric plexus, which is the intrinsic neural network principally responsible for the coordination of muscular activity in the gut. This review focuses on the physiological circadian variation of major colonic functions and their entraining mechanisms, including colonic motility, absorption, hormone secretion, permeability, and pain signalling. Pathophysiological states such as irritable bowel syndrome and ulcerative colitis and their interactions with circadian rhythmicity are also described. Finally, the classic circadian hormone melatonin is discussed, which is expressed in the gut in greater quantities than the pineal gland, and whose exogenous use has been of therapeutic interest in treating colonic pathophysiological states, including those exacerbated by chronic circadian disruption.
Language	English
Publishing date	2023-08-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2023.1239278
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Article ; Online: Abnormal Perception of Urge to Defecate: An Important Pathophysiological Mechanism in Women With Chronic Constipation.

Vollebregt, Paul F / Wiklendt, Lukasz / Burgell, Rebecca E / Chaichanavichkij, Pam / Dinning, Phil G / Knowles, Charles H / Scott, S Mark

The American journal of gastroenterology

2022 Volume 117, Issue 7, Page(s) 1125–1136

Abstract: ... 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 ... score: 19 vs 15 P < 0.0001), irritable bowel syndrome (45.7% vs 22.9% P < 0.0001), and a functional ...

Abstract	Introduction: 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). Methods: 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). Results: 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. Discussion: 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.
MeSH term(s)	Adult ; Bayes Theorem ; Constipation ; Defecation/physiology ; Female ; Humans ; Male ; Manometry ; Perception ; Prospective Studies ; Rectum
Language	English
Publishing date	2022-04-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	390122-1
ISSN	1572-0241 ; 0002-9270
ISSN (online)	1572-0241
ISSN	0002-9270
DOI	10.14309/ajg.0000000000001794
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Article ; Online: Faecal incontinence is associated with an impaired rectosigmoid brake and improved by sacral neuromodulation.

Lin, Anthony Y / Varghese, Chris / Paskaranandavadivel, Niranchan / Seo, Sean / Du, Peng / Dinning, Phil / Bissett, Ian P / O'Grady, Greg

Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland

2022 Volume 24, Issue 12, Page(s) 1556–1566

Abstract: ... 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 ... h premeal with SNM, p = 0.028). Consuming a meal did not further increase the number of propagating ...

Abstract	Background: 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. Methods: 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. Results: 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. Conclusion: The rectosigmoid brake was suppressed in this cohort of patients with faecal incontinence. SNM may exert a therapeutic effect by modulating this rectosigmoid brake.
MeSH term(s)	Humans ; Fecal Incontinence/therapy ; Treatment Outcome ; Rectum ; Colon ; Electric Stimulation Therapy ; Lumbosacral Plexus
Language	English
Publishing date	2022-07-19
Publishing country	England
Document type	Journal Article
ZDB-ID	1440017-0
ISSN	1463-1318 ; 1462-8910
ISSN (online)	1463-1318
ISSN	1462-8910
DOI	10.1111/codi.16249
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Article ; Online: High resolution colonic manometry--what have we learnt?--A review of the literature 2012.

Bampton, P A / Dinning, P G

Current gastroenterology reports

2013 Volume 15, Issue 6, Page(s) 328

Abstract: ... within the colon in real time (Dinning and Scott (Curr Opin Pharmacol 11:624-629, 2011)). Based upon data ...

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 amplitude propagating sequences (contractions), (2) low amplitude 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.
MeSH term(s)	Colon/physiopathology ; Colonic Diseases/diagnosis ; Colonic Diseases/physiopathology ; Gastrointestinal Motility/physiology ; Humans ; Manometry/methods
Language	English
Publishing date	2013-05-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2041376-2
ISSN	1534-312X ; 1522-8037
ISSN (online)	1534-312X
ISSN	1522-8037
DOI	10.1007/s11894-013-0328-2
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Article ; Online: The effects of loperamide on excitatory and inhibitory neuromuscular function in the human colon.

Heitmann, Paul T / Keightley, Lauren / Wiklendt, Lukasz / Wattchow, David A / Brookes, Simon S J / Spencer, Nicholas J / Costa, Marcello / Dinning, Phil G

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society

2022 Volume 34, Issue 11, Page(s) e14442

Abstract: ... isometric relaxation during EFS (median difference + 0.60 g post-loperamide, Z = -2.35, p = 0.019 ...

Abstract	Background: 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. Methods: Tissue specimens of human colon from 10 patients undergoing an anterior resection were divided 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. Key results: 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). Conclusions and inferences: 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.
MeSH term(s)	Animals ; Colon ; Electric Stimulation ; Gastrointestinal Motility ; Humans ; Loperamide/pharmacology ; Muscle Contraction/physiology ; Naloxone/pharmacology ; Nitroarginine/pharmacology ; Scopolamine/pharmacology
Chemical Substances	Nitroarginine (2149-70-4) ; Naloxone (36B82AMQ7N) ; Loperamide (6X9OC3H4II) ; Scopolamine (DL48G20X8X)
Language	English
Publishing date	2022-08-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1186328-6
ISSN	1365-2982 ; 1350-1925
ISSN (online)	1365-2982
ISSN	1350-1925
DOI	10.1111/nmo.14442
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Article ; Online: The use of colonic and anorectal high-resolution manometry and its place in clinical work and in research.

Dinning, P G / Carrington, E V / Scott, S M

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society

2015 Volume 27, Issue 12, Page(s) 1693–1708

Abstract: Background: 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 ...

Abstract	Background: 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. Purpose: 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.
MeSH term(s)	Gastroenterology/methods ; Gastrointestinal Diseases/diagnosis ; Humans ; Manometry/methods
Language	English
Publishing date	2015-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1186328-6
ISSN	1365-2982 ; 1350-1925
ISSN (online)	1365-2982
ISSN	1350-1925
DOI	10.1111/nmo.12632
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Article ; Online: Screening for VACTERL Anomalies in Children with Anorectal Malformations: Outcomes of a Standardized Approach.

Evans-Barns, Hannah M E / Porrett, Liesel / Hartmann, Penelope L / Taranto, Jessica / Jackson-Fleurus, Suzie / Dinning, Phil G / Hutson, John M / Teague, Warwick J / King, Sebastian K

Journal of pediatric surgery

2023 Volume 58, Issue 7, Page(s) 1263–1268

Abstract: ... with those assessed prior to protocol implementation (RR 0.43 [CI 0.27-0.66]; p < 0.001). Children with less complex ... ARM types were significantly less likely to receive complete screening (p = 0.028). Neither presence ...

Abstract	Purpose: The majority of patients with an anorectal malformation (ARM) have associated congenital anomalies. It is well established that all patients diagnosed with an ARM should undergo systematic screening, including renal, spinal, and cardiac imaging. This study aimed to evaluate the findings and completeness of screening, following local implementation of standardized protocols. Methods: A retrospective cohort study was performed assessing all patients with an ARM managed at our tertiary pediatric surgical center, following a standardized protocol implementation for VACTERL screening (January 2016-December 2021). Cohort demographics, medical characteristics, and screening investigations were analyzed. Findings were compared with our previously published data (2000-2015), conducted prior to protocol implementation. Results: One hundred twenty-seven (64 male, 50.4%) children were eligible for inclusion. Complete screening was performed in 107/127 (84.3%) children. Of these, one or more associated anomalies were diagnosed in 85/107 (79.4%), whilst the VACTERL association was demonstrated in 57/107 (53.3%). The proportion of children that underwent complete screening increased significantly in comparison with those assessed prior to protocol implementation (RR 0.43 [CI 0.27-0.66]; p < 0.001). Children with less complex ARM types were significantly less likely to receive complete screening (p = 0.028). Neither presence of an associated anomaly, nor prevalence of the VACTERL association, differed significantly by ARM type complexity. Conclusion: Screening for associated VACTERL anomalies in children with ARM was significantly improved following standardized protocol implementation. The prevalence of associated anomalies in our cohort supports the value of routine VACTERL screening in all children with ARM, regardless of malformation type. Level of evidence: II.
MeSH term(s)	Humans ; Male ; Child ; Anorectal Malformations/diagnosis ; Anorectal Malformations/epidemiology ; Retrospective Studies ; Limb Deformities, Congenital/diagnosis ; Limb Deformities, Congenital/epidemiology ; Heart Defects, Congenital/diagnosis ; Heart Defects, Congenital/epidemiology ; Anal Canal/abnormalities ; Spine/abnormalities
Language	English
Publishing date	2023-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	80165-3
ISSN	1531-5037 ; 0022-3468
ISSN (online)	1531-5037
ISSN	0022-3468
DOI	10.1016/j.jpedsurg.2023.01.051
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