Biomedical subjects

Daniela Vieten

Publications and source records attributed to Daniela Vieten.

3 recordsLinked to original sources

PubMed2006

Proliferative response in necrotising enterocolitis is insufficient to prevent disease progression.

Necrotising enterocolitis (NEC) is characterised by severe mucosal loss and therefore gastrointestinal (GI) cell proliferation is essential for survival, epithelial repair and recovery of function. Trefoil peptides play a key role in epithelial restitution and repair, and we previously reported a down-regulation of these peptides in NEC. Oral administration of epidermal growth factor has a protective effect in a rat model of colitis. These observations raised the question of a link between the pathogenesis of NEC and decreased mucosal cell proliferation. This study investigates the pattern of mucosal cell proliferation in the GI tract of fetuses, normal neonatal controls, infants with NEC and those recovering from NEC. Parents of neonates up to 44 weeks' gestation undergoing laparotomy and bowel resection were approached for consent. Bowel samples from resection specimens, and GI tract extractions from products of conception at termination of pregnancy, were fixed in formalin and then embedded in paraffin blocks. Patterns of small and large bowel mucosal proliferation were assessed by immunohistochemical staining for Ki67. Seventeen foetal and 58 postnatal bowel samples [34 with NEC (22 acute, 12 recovery) and 24 controls] were analysed. The pattern of proliferation seen in the fetus and normal neonate was identical to that in mature bowel. In NEC severe mucosal necrosis was observed, but in viable crypts remaining, there was crypt hyperplasia and a relative increase in the proportion of cells staining positive for Ki67. In those patients recovering from NEC the pattern of proliferation was returning towards the normal range. In those patients with post-NEC strictures the recovery of normal bowel morphology was delayed. In NEC there is massive loss of potential proliferative tissue. The remaining viable tissue shows an increase in proliferative activity in the small and large bowel. Failure of rapid regeneration of functional mucosa may therefore be related to an inability of increased proliferative activity to match the losses from the surface; alternatively there may be rapid production of immature, short-lived cells. This study shows that the proliferative response, although present, is insufficient to rapidly reverse the mucosal insult observed in NEC.

Analysis of Variance↗

PubMed2004

Impaired mucosal regeneration in neonatal necrotising enterocolitis.

Necrotising enterocolitis (NEC) remains an overwhelming gastrointestinal (GI) emergency in premature infants, with an annual incidence of 350 cases and a mortality of 23% in the United Kingdom. The aetiology of NEC is multifactorial and its pathogenesis poorly understood. It is characterised by severe necrotic damage to the intestine. Mucus is an adherent, viscoelastic gel layer protecting the delicate underlying epithelium from lumenal aggressors such as digestive enzymes and bacterial toxins. The group of trefoil factor peptides (TFF1-3) are part of the protective mechanism operating in the intestinal mucosa and play a fundamental role in epithelial protection, repair, and restitution. These secreted peptides have been identified in a site-specific pattern in the GI mucosa, and their expression has been shown to be upregulated in early stages of mucosal repair. The role of trefoil peptides in neonatal mucosal protection has not been well investigated. Impaired mucosal regeneration due in part to failure of upregulation of TFF expression may contribute to the pathogenesis of NEC. The aim of this study was to investigate TFF1-3 mRNA expression and to identify the gene product in the GI tracts of normal neonatal controls and infants with NEC. Parents of all babies having a laparotomy in the neonatal period (defined as up to 44 weeks' gestation) and bowel resection were approached for written consent. Bowel samples were fixed in formalin and then embedded in paraffin in an RNAse-free manner. In situ hybridisation and immunohistochemistry were performed to examine the pattern of trefoil mRNA expression and to localise the peptides in the neonatal GI tract. Forty neonatal bowel specimens were examined. Twelve patients had NEC, eight were recovering from NEC, and 20 control specimens were obtained. TFF1 and TFF2 mRNA expression were not detected in the majority of NEC specimens, and there was a relative downregulation of TFF3 expression in 83% of NEC patients. TFF1 and TFF2 expression were noted in the recovery phase from NEC. Immunohistochemistry revealed a decrease in TFF3 gene product in sites adjacent to mucosal damage secondary to NEC. In acute NEC there was no apparent expression of TFF1 and 2 protein. In the group of patients recovering from NEC, TFF1 and 2 expression were seen in association with regenerative changes in the mucosa. Previous data has shown TFF1-3 to be upregulated in the acute phase response to mucosal injury in the gut. Trefoil peptides have been shown to promote epithelial cell migration and protect against apoptosis. Our results suggest that there is a lack of TFF expression in response to NEC in the premature gut. This may lead to impaired restitution of the mucosa and contribute to the cascade of bowel necrosis and generalised sepsis characteristic of NEC.

Adult↗

PubMed2004

Enterocolitis complicating Hirschsprung's disease.

Enterocolitis remains a relatively common complication of Hirschsprung's disease with significant morbidity and mortality. The etiology of Hirschsprung's enterocolitis (HEC) is multifactorial and remains poorly understood. Preventative measures and better treatment modalities will evolve out of a better understanding of the underlying pathophysiology. Prompt recognition of HEC allows early intervention and a potential reduction in disease severity and mortality. This review of HEC describes the epidemiology, clinical and pathological features and current best practice in management. Some of the areas of research into etiology and treatment are discussed.

Biopsy, Needle↗