{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:11:58Z","timestamp":1791223918628,"version":"4.1.0"},"reference-count":69,"publisher":"BMJ","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[1998,12,1]]},"published-print":{"date-parts":[[1999,5,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Nitric oxide is the most important transmitter in non-adrenergic non-cholinergic nerves in the human gastrointestinal tract. Impaired nitrergic innervation has been described in Hirschsprung\u2019s disease, hypertrophic pyloric stenosis, and intestinal neuronal dysplasia (IND). Recent findings indicate that hyperganglionosis, one of the major criteria of IND, is age dependent. However, information is scanty regarding the neurone density in normal human bowel in the paediatric age group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>AIMS<\/jats:title>\n                    <jats:p>To determine neurone density, morphology, and nitric oxide synthase distribution of the normal myenteric plexus at different ages during infancy and childhood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec sec-type=\"methods\">\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Specimens were obtained from small bowel and colon in 20 children, aged one day to 15 years, at postmortem examination. Whole mount preparations were made of the myenteric plexus, which were subsequently stained using NADPH diaphorase histochemistry (identical to nitric oxide synthase) and cuprolinic blue (a general neuronal marker). The morphology of the myenteric plexus was described and the neurone density estimated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The myenteric plexus meshwork becomes less dense during the first years of life. The density of ganglion cells in the myenteric plexus decreases significantly with age during the first three to four years of life. The NADPH diaphorase positive (nitrergic) subpopulation represents about 34% of all neurones in the myenteric plexus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The notable decrease in neurone density in the myenteric plexus during the first years of life indicates that development is still an ongoing process in the postnatal enteric nervous system. Applied to the clinical situation, this implies that interpretation of enteric nervous system pathology is dependent on the age of the patient.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gut.44.5.666","type":"journal-article","created":{"date-parts":[[2010,6,30]],"date-time":"2010-06-30T12:46:12Z","timestamp":1277901972000},"page":"666-674","source":"Crossref","is-referenced-by-count":109,"title":["Notable postnatal alterations in the myenteric plexus of normal human bowel"],"prefix":"10.1136","volume":"44","author":[{"given":"T","family":"Wester","sequence":"first","affiliation":[{"name":"Children\u2019s Research Centre, Our Lady\u2019s Hospital for Sick Children, Crumlin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D S","family":"O\u2019Briain","sequence":"additional","affiliation":[{"name":"Children\u2019s Research Centre, Our Lady\u2019s Hospital for Sick Children, Crumlin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Puri","sequence":"additional","affiliation":[{"name":"Children\u2019s Research Centre, Our Lady\u2019s Hospital for Sick Children, Crumlin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1999,5,1]]},"reference":[{"key":"2025121304295424000_44.5.666.1","first-page":"G379","article-title":"Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission.","volume":"262","author":"Sanders","year":"1992","journal-title":"Am J Physiol"},{"key":"2025121304295424000_44.5.666.2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(83)90085-7"},{"key":"2025121304295424000_44.5.666.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.17.7797"},{"key":"2025121304295424000_44.5.666.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.7.2811"},{"key":"2025121304295424000_44.5.666.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199208203270802"},{"key":"2025121304295424000_44.5.666.6","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/0016-5085(93)90938-9","article-title":"Nitric oxide synthase distribution in the enteric nervous system of Hirschsprung\u2019s disease.","volume":"105","author":"Vanderwinden","year":"1993","journal-title":"Gastroenterology"},{"key":"2025121304295424000_44.5.666.7","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3468(94)90336-0"},{"key":"2025121304295424000_44.5.666.8","unstructured":"Kobayashi H, Hirakawa H, Puri P. Intestinal neuronal dysplasia. Is acetylcholinesterase histochemistry adequate for diagnosis? In: XXXXI Annual International Congress of British Association of Paediatric Surgeons, Rotterdam, 1994. ."},{"key":"2025121304295424000_44.5.666.9","first-page":"506","article-title":"\u00dcber ein Erkrankungsbild des Colon mit Hirschsprung-Symptomatik.","volume":"55","author":"Meier-Ruge","year":"1971","journal-title":"Vehr Dtsch Ges Pathol"},{"key":"2025121304295424000_44.5.666.10","first-page":"537","article-title":"Intestinal neuroneal dysplasia. Why does it only occur in parts of Europe?","volume":"426","author":"Lake","year":"1995","journal-title":"Virchows Arch"},{"key":"2025121304295424000_44.5.666.11","first-page":"356","article-title":"Intestinal neuronal dysplasia.","volume":"17","author":"Milla","year":"1993","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"2025121304295424000_44.5.666.12","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1055\/s-2008-1066116","article-title":"The neuropathological diagnosis of neuronal intestinal dysplasia (NID B).","volume":"4","author":"Meier-Ruge","year":"1994","journal-title":"Eur J Pediatr Surg"},{"key":"2025121304295424000_44.5.666.13","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/BF00192108","article-title":"Histopathological criteria for intestinal neuronal dyplasia of the submucosal plexus (type B).","volume":"426","author":"Meier-Ruge","year":"1995","journal-title":"Virchows Arch"},{"key":"2025121304295424000_44.5.666.14","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0185(199604)244:4<470::AID-AR5>3.0.CO;2-Z"},{"key":"2025121304295424000_44.5.666.15","first-page":"461","article-title":"NADPH diaphorase-containing nerve fibers and neurones in the myenteric plexus are resistant to postmortem changes.","volume":"122","author":"Wester","year":"1998","journal-title":"Arch Pathol Lab Med"},{"key":"2025121304295424000_44.5.666.16","doi-asserted-by":"publisher","DOI":"10.1007\/BF01003974"},{"key":"2025121304295424000_44.5.666.17","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(87)90101-4"},{"key":"2025121304295424000_44.5.666.18","unstructured":"Furness JB Costa M , eds (1987) Cytoarchitectonics of the enteric nervous system. The enteric nervous system. (Churchill Livingstone, New York, NY), pp 26\u201354."},{"key":"2025121304295424000_44.5.666.19","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(93)91003-Z"},{"key":"2025121304295424000_44.5.666.20","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(93)90943-7"},{"key":"2025121304295424000_44.5.666.21","doi-asserted-by":"publisher","DOI":"10.1136\/gut.34.5.689"},{"key":"2025121304295424000_44.5.666.22","first-page":"G73","article-title":"Vasoactive intestinal peptide as a neural mediator of gastric relaxation.","volume":"248","author":"Grider","year":"1985","journal-title":"Am J Physiol"},{"key":"2025121304295424000_44.5.666.23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1970.tb10646.x"},{"key":"2025121304295424000_44.5.666.24","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1983.sp014579"},{"key":"2025121304295424000_44.5.666.25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.22.7041"},{"key":"2025121304295424000_44.5.666.26","first-page":"G774","article-title":"Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release","volume":"262","author":"Grider","year":"1992","journal-title":"Am J Physiol"},{"key":"2025121304295424000_44.5.666.27","first-page":"G492","article-title":"Evidence for VIP-induced increase in NO production in myenteric neurones of opossum internal anal sphincter.","volume":"270","author":"Chadker","year":"1996","journal-title":"Am J Physiol"},{"key":"2025121304295424000_44.5.666.28","doi-asserted-by":"publisher","DOI":"10.1038\/347768a0"},{"key":"2025121304295424000_44.5.666.29","doi-asserted-by":"publisher","DOI":"10.1007\/BF00268875"},{"key":"2025121304295424000_44.5.666.30","first-page":"G277","article-title":"NADPH diaphorase and nitric oxide synthase colocalization in enteric neurones of canine proximal colon.","volume":"263","author":"Ward","year":"1992","journal-title":"Am J Physiol"},{"key":"2025121304295424000_44.5.666.31","doi-asserted-by":"publisher","DOI":"10.1007\/BF02053596"},{"key":"2025121304295424000_44.5.666.32","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)11655-G"},{"key":"2025121304295424000_44.5.666.33","doi-asserted-by":"publisher","DOI":"10.1177\/33.9.3926868"},{"key":"2025121304295424000_44.5.666.34","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1055\/s-2008-1066117","article-title":"Immunohistochemistry of markers of the enteric nervous system in whole-mount preparations of the human colon.","volume":"4","author":"Krammer","year":"1993","journal-title":"Eur J Pediatr Surg"},{"key":"2025121304295424000_44.5.666.35","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0940-9602(11)80433-4","article-title":"Distribution of NADPH-diaphorase-positive neurones in the enteric nervous system of the human colon.","volume":"176","author":"Krammer","year":"1994","journal-title":"Ann Anat"},{"key":"2025121304295424000_44.5.666.36","doi-asserted-by":"publisher","DOI":"10.1007\/BF00319421"},{"key":"2025121304295424000_44.5.666.37","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/0016-5085(89)91619-3","article-title":"Human myenteric plexus: confirmation of unfamiliar structures in adults and neonates.","volume":"96","author":"Kumar","year":"1989","journal-title":"Gastroenterology"},{"key":"2025121304295424000_44.5.666.38","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3468(94)90335-2"},{"key":"2025121304295424000_44.5.666.39","first-page":"127","article-title":"Histochemical and ultrastructural features of the developing enteric nervous system of the human foetal small intestine.","volume":"10","author":"Fekete","year":"1995","journal-title":"Histol Histopathol"},{"key":"2025121304295424000_44.5.666.40","first-page":"596","article-title":"Neuropathology of Hirschsprung\u2019s disease.","volume":"37","author":"Mebis","year":"1990","journal-title":"Hepatogastroenterology"},{"key":"2025121304295424000_44.5.666.41","doi-asserted-by":"publisher","DOI":"10.1007\/BF00543961"},{"key":"2025121304295424000_44.5.666.42","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/0016-5085(78)90476-6","article-title":"A familial neuronal disease presenting as intestinal pseudoobstruction.","volume":"75","author":"Schuffler","year":"1978","journal-title":"Gastroenterology"},{"key":"2025121304295424000_44.5.666.43","first-page":"52","article-title":"Hypogenesis of intestinal ganglion cells: a rare cause of intestinal obstruction simulating aganglionosis.","volume":"43","author":"Ikeda","year":"1988","journal-title":"Z Kinderchir"},{"key":"2025121304295424000_44.5.666.44","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3109\/15513819309048209","article-title":"Intestinal neuronal density in childhood: a baseline for the objective assessment of hypo- and hyperganglionosis.","volume":"13","author":"Smith","year":"1993","journal-title":"Pediatr Pathol"},{"key":"2025121304295424000_44.5.666.45","first-page":"254","article-title":"Das hypoganglion\u00e4re Megakolon als Begleitkrankheit bei Morbus Hirschsprung.","volume":"8","author":"Meier-Ruge","year":"1970","journal-title":"Z Kinderchir"},{"key":"2025121304295424000_44.5.666.46","first-page":"81","article-title":"Neuron size and number in the myenteric plexus of the newborn and adult rat.","volume":"109","author":"Gabella","year":"1971","journal-title":"J Anat"},{"key":"2025121304295424000_44.5.666.47","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(87)90369-1"},{"key":"2025121304295424000_44.5.666.48","first-page":"51","article-title":"A quantitative study on the myenteric plexus of the distal end of the duodenum and the proximal part of the jejunum.","volume":"129","author":"Ferraz de Carvalho","year":"1983","journal-title":"Gegenbaurs morph Jahrb, Leipzig"},{"key":"2025121304295424000_44.5.666.49","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1159\/000213532","article-title":"Age-induced nerve cell loss in the myenteric plexus of the small intestine in man.","volume":"39","author":"de Souza","year":"1993","journal-title":"Gerontology"},{"key":"2025121304295424000_44.5.666.50","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3468(93)90124-4"},{"key":"2025121304295424000_44.5.666.51","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1007\/BF01899135","article-title":"Detection of nerve cells by a histochemical technique.","volume":"25","author":"Gabella","year":"1969","journal-title":"Experientia"},{"key":"2025121304295424000_44.5.666.52","doi-asserted-by":"publisher","DOI":"10.1007\/BF00323587"},{"key":"2025121304295424000_44.5.666.53","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/0016-5085(94)90113-9","article-title":"The distribution of novel intermediate filament proteins defines subpopulations of myenteric neurones in rat intestine.","volume":"107","author":"Eaker","year":"1994","journal-title":"Gastroenterology"},{"key":"2025121304295424000_44.5.666.54","doi-asserted-by":"publisher","DOI":"10.1007\/BF01003343"},{"key":"2025121304295424000_44.5.666.55","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4179(95)90050-0"},{"key":"2025121304295424000_44.5.666.56","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v111.pm8690205"},{"key":"2025121304295424000_44.5.666.57","first-page":"65","article-title":"\u00dcber die in der Dickdarmswand aszendierenden Nervev des Plexus pelvinus und die Grense der vagalen und sakralparasympatischen Innervation.","volume":"84","author":"Stach","year":"1971","journal-title":"Z Mikrosk-Anat Forsch"},{"key":"2025121304295424000_44.5.666.58","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/S0016-5085(84)80120-1","article-title":"Comparative anatomy of the myenteric plexus of the distal colon in eight mammals.","volume":"86","author":"Christensen","year":"1984","journal-title":"Gastroenterology"},{"key":"2025121304295424000_44.5.666.59","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1113\/jphysiol.1984.sp015364","article-title":"The intramural pelvic nerves in the colon of dogs.","volume":"354","author":"Fukai","year":"1984","journal-title":"J Physiol"},{"key":"2025121304295424000_44.5.666.60","unstructured":"Furness JB Costa M , eds (1987) Studies of neuroneal circuitry of the enteric nervous system. The enteric nervous system. (Churchill Livingstone, New York, NY), pp 111\u2013136."},{"key":"2025121304295424000_44.5.666.61","unstructured":"Christensen J (1994) The motility of the colon. in Physiology of the gastrointestinal tract. ed Johnson LR (Raven Press, New York), pp 991\u20131024."},{"key":"2025121304295424000_44.5.666.62","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3468(98)90157-9"},{"key":"2025121304295424000_44.5.666.63","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3468(96)90669-7"},{"key":"2025121304295424000_44.5.666.64","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3468(68)90344-8"},{"key":"2025121304295424000_44.5.666.65","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.14.030191.002321"},{"key":"2025121304295424000_44.5.666.66","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1992.tb08328.x"},{"key":"2025121304295424000_44.5.666.67","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(94)90015-9"},{"key":"2025121304295424000_44.5.666.68","doi-asserted-by":"publisher","DOI":"10.1007\/BF00717050"},{"key":"2025121304295424000_44.5.666.69","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(96)70057-4"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.44.5.666","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T12:30:06Z","timestamp":1765629006000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.44.5.666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,5,1]]},"references-count":69,"journal-issue":{"issue":"5","published-online":{"date-parts":[[1999,5,1]]},"published-print":{"date-parts":[[1999,5,1]]}},"alternative-id":["10.1136\/gut.44.5.666"],"URL":"https:\/\/doi.org\/10.1136\/gut.44.5.666","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,5,1]]}}}