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  • 1
    Electronic Resource
    Electronic Resource
    Increased intracellular levels of calcitonin gene-related peptide-like immunoreactivity in pulmonary endocrine cells in an experimental model of congenital diaphragmatic hernia (1996)
    Springer
    Pediatric surgery international 11 (1996), S. 448-452 
    Details
    ISSN: 1437-9813
    Keywords: Congenital diaphragmatic hernia ; Newborn ; Pulmonary hypertension ; Calcitonin gene-related peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A congenital diaphragmatic hernia (CDH) model was induced in pregnant rats following administration of 100 mg nitrofen. The fetuses were stored and fixed in Bouin's solution for 24 h after caesarean section at term. After fixation, the lungs were dissected out. Immunostaining of the CDH lungs and controls with rabbit anti-rat calcitonin gene-related peptide (CGRP) antibody at “optimal” and “supraoptimal” dilution levels was obtained by examining the intensity of staining with a series of dilutions of the antisera from 1: 1,000 to 1: 20,000. Supraoptimal dilution detects variations in antigen concentration that may be masked if the routine optimal dilution is used. Immunostaining of the lung by antisera to platelet-derived growth factor (PDGF) and alpha-smooth-muscle actin (ASMA) was performed to examine vascular remodelling. The number of CGRP-immunoreactive cells was significantly (P 〈0.001) greater in the lungs of CDH rats (n = 26) (0.74 +-0.19 NEB [neuroepithelial bodies]/mm2; mean +- SEM) compared with controls (n = 21) (0.30+-0.16 NEB/mm2) seen at supraoptimal dilution (1:20,000). Since CGRP is a vasodilator, this could have important implications in the development of pulmonary hypertension. The pattern of ASMA and PDGF immunostaining was similar in CDH lungs and controls, and therefore, vascular remodelling is not a feature of CDH lungs in fetuses delivered by caesarean section and not exposed to hypoxia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00180080
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  • 2
    Electronic Resource
    Electronic Resource
    Mutations of the endothelin-B receptor and endothelin-3 genes in Hirschsprung's disease (1996)
    Springer
    Pediatric surgery international 12 (1996), S. 19-23 
    Details
    ISSN: 1437-9813
    Keywords: Hirschsprung's disease ; Endothelin-B receptor gene ; Endothelin-3 gene ; Mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The endothelin-B receptor gene (EDNRB) and the endothelin-3 gene (EDN3) have recently been recognized as susceptibility genes for Hirschsprung's disease (HD). Novel EDNRB mutations have been detected in non-syndrommc HD patients with heterozygous forms, and homozygous mutations of the EDNRB or the EDN3 genes have been reported in HD patients associated with type 2 Waardenburg syndrome. These observations confirm that impaired function of the endothelin-B receptor or endothelin-3 is involved in the aetiology of some human HD cases. EDNRB mutations appear to be associated with shortsegment HD, in contrast to RET mutations, which are found mainly in long-segment aganglionosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01194795
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  • 3
    Electronic Resource
    Electronic Resource
    Active collagen synthesis in infantile hypertrophic pyloric stenosis (1998)
    Springer
    Pediatric surgery international 13 (1998), S. 237-239 
    Details
    ISSN: 1437-9813
    Keywords: Key words Infantile hypertrophic pyloric stenosis ; Procollagen type I extracellular matrix ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract M-57 antibody, which is capable of distinguishing newly-synthesized type I procollagen from fully-processed, mature collagen, was used to examine the expression of collagen synthesis in hypertrophic pyloric muscle from patients with infantile hypertrophic pyloric stenosis (IHPS). Seven specimens from IHPS patients were removed at the time of operation; age-matched normal pyloric tissue of 5 post-mortem cases was obtained as controls. Immunohistochemistry was performed using antibody of the amino-terminal end of the procollagen type I propeptide (M-57). Newly-synthesized procollagen (M-57) was strongly detected in both the connective tissue septa between circular muscle bundles, and among the circular-muscle fibers in patients with IHPS. No M-57 staining was observed among the circular-muscle fibers in controls. Our findings show that the hypertrophic circular muscle in IHPS is actively synthesizing collagen, and this may be responsible for the characteristic “firm” nature of the pyloric tumor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050306
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  • 4
    Electronic Resource
    Electronic Resource
    Altered intramuscular innervation and synapse formation in internal sphincter achalasia (1999)
    Springer
    Pediatric surgery international 15 (1999), S. 192-194 
    Details
    ISSN: 1437-9813
    Keywords: Keywords Internal anal sphincter achalasia ; Innervation ; PGP 9.5 ; Synapse ; Synapsin I ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Internal anal sphincter achalasia (IASA) is a condition with a clinical presentation similar to Hirschsprung's disease, but with the presence of ganglion cells on rectal biopsy. The diagnosis of IASA is made on anorectal manometry, which demonstrates the absence of a rectosphincteric reflux on rectal balloon inflation. In order to understand the nature of neuronal abnormalities in this condition, we performed immunohistochemistry using PGP 9.5 (a general neuronal marker) and synapsin I (a presynaptic marker) in IAS specimens from 10 patients with IASA and 8 normal controls. In the IAS of normal controls, there were many PGP 9.5 and synapsin I-positive nerve fibers. In IASA PGP 9.5-immunoreactive fibers were markedly reduced and synapsin I-positive fibers were either absent or markedly reduced. Our findings demonstrate that the IAS in achalasia patients has defective intramuscular innervation as well as defective innervation of the neuromuscular junction, thereby contributing to the motility dysfunction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050552
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  • 5
    Electronic Resource
    Electronic Resource
    Neonatal intestinal perforation in Hirschsprung's disease (1994)
    Springer
    Pediatric surgery international 9 (1994), S. 501-502 
    Details
    ISSN: 1437-9813
    Keywords: Hirschsprung's disease ; Intestinal perforation ; Neonate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Over a period of 18 years, 77 of 135 patients treated for Hirschsprung's disease (HD) presented in the neonatal period. Of these 77 patients, 8 had gastrointestinal (GI) perforations. Seven patients were born at full term and 1 at 32 weeks of gestation. Three patients had associated trisomy 21. The site of perforation included rectum in 1 patient, sigmoid in 1, descending colon in 1, transverse colon in 2, caecum in 2, and jejunum in 1. Perforations occurred in ganglionic bowel in 7 patients and in the aganglionic segment in 1. One patient died in the newborn period of overwhelming sepsis secondary to enterocolitis, and histology of the bowel confirmed HD. In 6 patients HD was confirmed on barium enema and suction rectal biopsy, and they subsequently underwent a definitive pull-through operation. The 1 patient in whom the initial barium enema was normal continued to suffer from constipation until the age of 7 years, when the diagnosis of HD was established. He then underwent a pull-through procedure with no further problems. An association between neonatal intestinal perforation and HD must therefore be recognised to avoid delay in the management.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00179451
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  • 6
    Electronic Resource
    Electronic Resource
    What are the diagnostic criteria for intestinal neuronal dysplasia? (1995)
    Springer
    Pediatric surgery international 10 (1995), S. 459-464 
    Details
    ISSN: 1437-9813
    Keywords: Intestinal neuronal dysplasia ; Hirschsprung's disease ; Acetylcholinesterase staining ; Diagnostic criteria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The incidence of isolated intestinal neuronal dysplasia (IND) has varied from 0.3% to 62% of all suction rectal biopsies in different centres. The uncertainty regarding the incidence has resulted from the considerable confusion regarding the essential diagnostic criteria. In an attempt to clarify the diagnostic criteria for IND, we examined biopsy material from the following three groups using acetylcholinesterase (AChE) histochemistry: (1) full-thickness normal colon from 23 controls; (2) suction rectal biopsies from 9 patients who had isolated IND; and (3) full-thickness biopsies from 10 patients with Hirschsprung's disease (HD) who demonstrated IND in the proximal margin of the resected segment. Our data show that hyperganglionosis is the most consistent finding in both IND associated with HD and isolated IND. Other histochemical criteria of IND were dependent upon whether the biopsy was full-thickness or a suction rectal biopsy. Where full-thickness biopsies were available, giant ganglia and ectopic ganglion cells were seen in all cases. Increases in AChE-positive nerve fibres in the mucosa was a frequent finding in patients with IND diagnosed by suction rectal biopsies. We recommend that patients suspected to have IND on suction rectal biopsy should have a full-thickness biopsy for detailed examination of the submucous and myenteric plexuses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00176387
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  • 7
    Electronic Resource
    Electronic Resource
    Antenatal dexamethasone improves atrial natriuretic peptide receptors in hypoplastic lung in nitrofen-induced diaphragmatic hernia in rats (2000)
    Springer
    Pediatric surgery international 16 (2000), S. 252-255 
    Details
    ISSN: 1437-9813
    Keywords: Key words Atrial natriuretic peptide ; Congenital diaphragmatic hernia ; Hypoplastic lung ; Reverse transcription polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Atrial natriuretic peptide (ANP) plays a major role in electrolyte and volume homeostasis through potent biological effects including vasorelaxation, bronchorelaxation, lung permeability, and clearance. There are two distinct biochemical and functional classes of ANP receptors, guanylate cyclase receptor (GC-R) and clearance receptors (clearance-R). Two subtypes of GC-R have been described, GCA-R and GCB-R. Antenatal glucocorticoid therapy (AGT) has been demonstrated to improve pulmonary immaturity and abnormal structure of pulmonary arteries in animal models of congenital diaphragmatic hernia (CDH). The aim of this study was to investigate the effect of antenatal glucocorticoid administration on the ANP system in nitrofen-induced CDH hypoplastic lung in rats. A CDH model was induced in pregnant rats following administration of nitrofen on day 9.5 of gestation. Dexamethasone (Dex) was given intraperitoneally on days 18.5 and 19.5; cesarean section was performed on day 21. Reverse transcription polymerase chain reaction was performed to evaluate the relative amounts of GCA-R, GCB-R and clearance-R mRNA expression. The mRNA expression of GCA-R, GCB-R, and clearance-R was significantly increased in CDH compared to control lung. ANP receptor mRNA expression was significantly decreased in CDH lung with compared to without Dex treatment. Our finding of increased ANP receptor mRNA expression in CDH lung suggests that the hypoplastic lung has high sensitivity for ANP. Decreased mRNA expression of ANP receptors in CDH lung after Dex treatment suggests that AGT may improve pulmonary physiological function of ANP in hypoplastic CDH lung.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050739
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  • 8
    Electronic Resource
    Electronic Resource
    The innervation of human bowel mucosa and its alterations in Hirschsprung's disease using a whole-mount preparation technique (2000)
    Springer
    Pediatric surgery international 16 (2000), S. 277-281 
    Details
    ISSN: 1437-9813
    Keywords: Key words Mucosal innervation ; Whole-mount preparation ; Hirschsprung's disease ; Suction rectal biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The innervation of the human bowel wall and its structural and functional changes in Hirschsprung's disease (HD) are well-recognised. The luminal surface of the bowel acts as a multifunctional barrier, and modifications in its physiochemical properties can result in serious complications such as enterocolitis (EC). The whole-mount preparation (WMP) technique produces a three-dimensional (3D) picture to better demonstrate the neuronal networks and the relationship of branching and interconnecting nerve fibres to each other. The aim of this study was to investigate the innervation of the mucosal layer in normal and HD bowel using a WMP immunohistochemistry technique in order to better understand the pathophysiology of HD. Full-thickness bowel specimens were collected from 9 HD patients at pull-through operation. Normal control small- and large-bowel specimens were collected from 10 patients at the time of bladder augmentation. Suction rectal biopsies from 8 patients with chronic constipation and 2 patients with HD were also included in this study. A WMP of the mucosal layer was made and stained with various neuronal markers (S100, PGP 9.5, and LlCAM) using fluorescein immunohistochemistry. PGP 9.5, S100, and LlCAM immunofluorescence staining of the normal mucosa demonstrated a characteristic 3D meshlike neuronal network of uniform thickness surrounding the crypts. In the aganglionic bowel S100, PGP 9.5, and LlCAM-positive meshlike networks were replaced by thick nerve trunks in the muscosa without any interconnecting network. The present study demonstrates for the first time the 3D morphology of mucosal innervation in normal and aganglionic bowel. The WMP technique clearly demonstrated that the mucosal innervation in HD is morphologically abnormal, and this may adversely influence secretory and absorptive functions of the bowel. WMPs using suction rectal biopsy specimens may be a useful additional technique to diagnose HD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050744
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  • 9
    Electronic Resource
    Electronic Resource
    Structural immaturity of the pylorus muscle in infantile hypertrophic pyloric stenosis (2000)
    Springer
    Pediatric surgery international 16 (2000), S. 282-284 
    Details
    ISSN: 1437-9813
    Keywords: Key words Desmin ; Infantile hypertrophic pyloric stenosis ; Immunohistochemistry ; Fetus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent reports indicate that extracellular matrix and cytoskeleton plasmalemmal elements are altered in infantile hypertrophic pyloric stenosis (IHPS). Desmin is a cytoskeletal protein that is important for the organization and function of muscular fibers. It has been found to be increased in the smooth muscle in chronic intestinal pseudo-obstruction and in skeletal muscle in some forms of myopathies as well as in unexplained hypertrophic cardiomyopathies. The aim of this study was to analyze the expression of desmin in IHPS. Full-thickness muscle-biopsy specimens were obtained from 8 IHPS patients (age range 23 to 41 days) at pyloromyotomy, from 8 age-matched controls without evidence of gastrointestinal (GI) disease at autopsy, and from 2 stillborns who died at 27 and 30 weeks of gestation without evidence of GI disease. Indirect immunohistochemistry was performed using the avidin-biotin-peroxidase complex method with anti-desmin and visualized by development with 3-diaminobenzidine tetrahydrochloride. Pyloric muscle in IHPS demonstrated strong desmin immunoreactivity. The expression of desmin was also strong in the muscular layers of fetal pylorus. In the age-matched controls absent or weak desmin immunoreactivity was seen in the pyloric muscle layer. The increased amount of desmin in hypertrophied pyloric muscle in IHPS may result in inco-ordination of contraction and relaxation of the pylorus, thus causing motility dysfunction. The similar pattern of desmin expression in IHPS and fetal pylorus suggests that the organization of intermediate filaments in IHPS is in a fetal stage of development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050745
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  • 10
    Electronic Resource
    Electronic Resource
    Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of enterocolitis complicating Hirschsprung's disease (1994)
    Springer
    Pediatric surgery international 9 (1994), S. 237-241 
    Details
    ISSN: 1437-9813
    Keywords: Hirschsprung's disease ; Enterocolitis ; Intercellular adhesion molecule-1 (ICAM-1)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein that is necessary for the transendothelial migration of leucocytes. This study was undertaken to elucidate the role of ICAM-1 in the pathophysiology of Hirschsprung's disease (HD)-related enterocolitis. Ganglionic and aganglionic portions of bowel from 18 patients with HD who did not have clinical or histological evidence of enterocolitis and 5 patients with HD who developed enterocolitis before or after a pull-through operation were stained using monoclonal antibody against ICAM-1. The bowel specimens obtained from 2 children with imperforate anus at the time of colostomy closure and 3 children at the time of bladder augmentation were similarly stained to act as controls. The ganglionic portion of bowel from patients with HD without enterocolitis and controls showed either no ICAM-I staining or occasional staining of the endothelial lining of submucosal vessels with no staining of the glandular crypt epithelium. In contrast, both ganglionic and aganglionic bowel from patients with enterocolitis complicating HD demonstrated strong ICAM-1 staining in the endothelium of submucosal vessels. Strong expression of ICAM-1 in the glandular crypt epithelium was seen in only 2 patients who had developed enterocolitis before pull-through operations. This study illustrates the importance of endothelial cell activation in the pathogenesis of HD-related enterocolitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00832246
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