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Dive into the research topics where Sebastian K. King is active.

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Featured researches published by Sebastian K. King.


The American Journal of Gastroenterology | 2008

24-Hour Colonic Manometry in Pediatric Slow Transit Constipation shows Significant Reductions in Antegrade Propagation

Sebastian K. King; Anthony G. Catto-Smith; Michael P. Stanton; Jonathan Sutcliffe; Dianne Simpson; Ian J. Cook; Phil Dinning; John M. Hutson; Bridget R. Southwell

BACKGROUND: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.METHODS: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).RESULTS: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 amplitude 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 amplitude 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.CONCLUSIONS: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.


Neurogastroenterology and Motility | 2010

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

Sebastian K. King; Jonathan Sutcliffe; Sim Ye Ong; M. Lee; T. L. Koh; S. Q. Wong; Pam Farmer; C. J. Peck; Michael P. Stanton; J. Keck; David J. Cook; C. W. Chow; John M. Hutson; Bridget R. Southwell

Background  Slow‐transit constipation (STC) is recognized in children but the etiology is unknown. Abnormalities in substance P (SP), vasoactive intestinal peptide (VIP) and nitric oxide (NO) have been implicated. The density of nerve fibers in circular muscle containing these transmitters was examined in colon from children with STC and compared to other pediatric and adult samples.


Journal of Pediatric Surgery | 2012

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

Melanie C.C. Clarke; Anthony G. Catto-Smith; Sebastian K. King; Philip G. Dinning; Ian J. Cook; Janet Chase; Susan Gibb; Val J. Robertson; Di Simpson; John M. Hutson; Bridget R. Southwell

BACKGROUND AND AIMS 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. METHODS 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. RESULTS 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 amplitude PS (HAPS/24h, 5 ± 2:10 ± 3, p=0.04), with amplitude, velocity, or propagating distance unchanged. There was increased activity on waking and 4/8 ceased using antegrade continence enemas. CONCLUSIONS AND INFERENCES 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.


Pediatric Surgery International | 2009

Slow-transit constipation in children: our experience

John M. Hutson; Janet Chase; Melanie C.C. Clarke; Sebastian K. King; Jonathan Sutcliffe; Susie Gibb; Anthony G. Catto-Smith; Val J. Robertson; Bridget R. Southwell

Constipation is a common problem in children, with childhood prevalence estimated at between 1 and 30%. It accounts for a significant percentage of referrals to paediatricians and paediatric gastroenterologists. It commonly runs in families, suggesting either an underlying genetic predisposition or common environmental factors, such as dietary exposure. The peak age for presentation of constipation is shortly after toilet training, when passage of hard stools can cause pain on defecation, which then triggers holding-on behaviour in the child. At the time of the next call to stool the toddler may try to prevent defecation by contraction of the pelvic floor muscles and anal sphincter. Unless the holding-on behaviour is quickly corrected by interventions to soften faeces and prevent further pain, the constipation can very rapidly become severe and chronic. Until recently, this mechanism was thought to be the only significant primary cause of constipation in childhood. In this review, we will summarise recent evidence to suggest that severe chronic constipation in children may also be due to slowed colonic transit.


Neurogastroenterology and Motility | 2009

Fall in density, but not number of myenteric neurons and circular muscle nerve fibres in guinea-pig colon with ageing.

C. J. Peck; S. D. Samsuria; Andrea M. Harrington; Sebastian K. King; John M. Hutson; Bridget R. Southwell

Abstract  In guinea‐pig ileum, ageing has been associated with a decrease in enteric neurons. This study examined guinea‐pig colon and measured changes in gut dimensions, neuron size, density and ganglionic area. Changes in motor nerve fibres in the circular muscle were also measured. Myenteric neurons in whole‐mount preparations of mid‐colon from 2‐week, 6‐month, and 2‐year‐old guinea‐pigs were labelled immunohistochemically with the neuronal marker human neuronal protein HuC/HuD, and numbers of neurons mm−2, neuronal size, ganglionic area mm−2, gut length, circumference and muscle thickness were measured. Corrected numbers of neurons mm−2 and ganglionic area mm−2 accounting for growth of the colon were calculated. Additionally, nerve fibres in circular muscle cross‐sections were labelled with antibodies against nitric oxide synthase (NOS) and substance P (SP) and the density of nerve fibres in circular muscle was measured. The numbers of neurons mm−2 decreased by 56% (from 2 weeks to 2 years) with no change in neuron size. Total neuron numbers decreased by 19% (P = 0.14) when adjusted for changes in length and circumference with age. The percentage area of NOS‐ and SP‐immunoreactive (IR) nerve fibres in the circular muscle decreased (P < 0.001), but the total area of NOS and SP‐IR nerve fibres increased (P < 0.01) due to an age‐related increase in muscle thickness. The density of myenteric neurons in guinea‐pig mid‐colon halved from 2 weeks to 2 years, but when the increase in colon dimensions was considered, the number of neurons decreased by only 19%. The percentage area of motor nerve fibres in the circular muscle decreased with no change in total volume of nerve fibres.


Pediatric and Developmental Pathology | 2006

Multiple Endocrine Neoplasia Type 2B Diagnosed on Suction Rectal Biopsy in Infancy: A Report of 2 Cases

Minzhi Yin; Sebastian K. King; John M. Hutson; C. W. Chow

Suction rectal biopsies in a newborn and a 10-month-old infant presenting with intestinal obstruction showed marked increase in neurons and nerve bundles in the submucosa. Although there were no syndromic features or a positive family history, mutation analysis of the RET proto-oncogene showed a de novo germline Met918Thr mutation in both patients, confirming the diagnosis of multiple endocrine neoplasia type 2B (MEN 2B). Thyroidectomy was performed at 9 and 14 months, showing medullary carcinoma and focal prominent C-cell hyperplasia, respectively. These 2 cases are presented to emphasize that when the submucosal plexus is obviously and prominently increased in suction rectal biopsies, diffuse intestinal ganglioneuromatosis should be considered. As this can be associated with genetic conditions, especially MEN 2B, it is crucial that further investigations be performed to ensure proper patient management, such as early thyroidectomy.


Cellular and molecular gastroenterology and hepatology | 2016

Enteric Neural Cells From Hirschsprung Disease Patients Form Ganglia in Autologous Aneuronal Colon

Benjamin N. Rollo; Dongcheng Zhang; Lincon A. Stamp; Trevelyan R. Menheniott; Lefteris Stathopoulos; Mirella Dottori; Sebastian K. King; John M. Hutson; Donald F. Newgreen

Background & Aims Hirschsprung disease (HSCR) is caused by failure of cells derived from the neural crest (NC) to colonize the distal bowel in early embryogenesis, resulting in absence of the enteric nervous system (ENS) and failure of intestinal transit postnatally. Treatment is by distal bowel resection, but neural cell replacement may be an alternative. We tested whether aneuronal (aganglionic) colon tissue from patients may be colonized by autologous ENS-derived cells. Methods Cells were obtained and cryopreserved from 31 HSCR patients from the proximal resection margin of colon, and ENS cells were isolated using flow cytometry for the NC marker p75 (nine patients). Aneuronal colon tissue was obtained from the distal resection margin (23 patients). ENS cells were assessed for NC markers immunohistologically and by quantitative reverse-transcription polymerase chain reaction, and mitosis was detected by ethynyl-2′-deoxyuridine labeling. The ability of human HSCR postnatal ENS-derived cells to colonize the embryonic intestine was demonstrated by organ coculture with avian embryo gut, and the ability of human postnatal HSCR aneuronal colon muscle to support ENS formation was tested by organ coculture with embryonic mouse ENS cells. Finally, the ability of HSCR patient ENS cells to colonize autologous aneuronal colon muscle tissue was assessed. Results ENS-derived p75-sorted cells from patients expressed multiple NC progenitor and differentiation markers and proliferated in culture under conditions simulating Wnt signaling. In organ culture, patient ENS cells migrated appropriately in aneural quail embryo gut, and mouse embryo ENS cells rapidly spread, differentiated, and extended axons in patient aneuronal colon muscle tissue. Postnatal ENS cells derived from HSCR patients colonized autologous aneuronal colon tissue in cocultures, proliferating and differentiating as neurons and glia. Conclusions NC-lineage cells can be obtained from HSCR patient colon and can form ENS-like structures in aneuronal colonic muscle from the same patient.


Neurogastroenterology and Motility | 2010

Decrease in nerve fibre density in human sigmoid colon circular muscle occurs with growth but not aging.

Bridget R. Southwell; T. L. Koh; S. Q. Wong; Sebastian K. King; Sim Ye Ong; M. Lee; Pam Farmer; C. J. Peck; Jonathan Sutcliffe; Michael P. Stanton; J. Keck; David J. Cook; C. W. Chow; John M. Hutson

Background  Studies in animals suggest that enteric neurons decrease in density or number with increasing age. Neurons containing nitric oxide (NO), vasoactive intestinal peptide (VIP) and Substance P (SP) have been implicated. In human large intestine, NO‐utilizing neurons decrease during childhood or early adulthood but it is not known if the innervation of the muscle changes. This study examined the density of nerve fibres containing these transmitters in sigmoid colon circular muscle from children and adults.


Seminars in Pediatric Surgery | 2010

What is new in radiology and pathology of motility disorders in children

Jonathan Sutcliffe; Sebastian K. King; John M. Hutson; Bridget R. Southwell

Disorders affecting colorectal motility lead to significant morbidity in children with surgical conditions. Etiology is frequently unknown, which in turn makes treatment empiric and compromises outcome. A thorough understanding of the normal mechanisms of control and the ability to recognize and manage defects is an important goal for clinicians. This article reviews recent advances made in the investigation of children with colorectal motility disorders, including the role of transit studies (marker studies and scintigraphy), options for assessing anatomy (ultrasound, contrast enema, and sectional imaging) and the use of manometry, both anorectal and colonic. Current concepts in microscopic evaluation are outlined.


Anz Journal of Surgery | 2004

Paediatric constipation for adult surgeons − article 1: targeting the cause

Jonathan Sutcliffe; Sebastian K. King; Bridget R. Southwell; John M. Hutson

Constipation is very common in all age groups and can be resistant to standard therapies, producing chronic morbidity. Childhood onset constipation frequently produces symptoms that persist into adulthood. Recent advances have been made in the diagnosis and treatment of childhood constipation that could have application in adult practice.

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John M. Hutson

Royal Children's Hospital

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Michael O'Brien

Royal Children's Hospital

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C. W. Chow

Royal Children's Hospital

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