Laparoscopic management of acute small bowel obstruction.

BACKGROUND: Conventional surgical management of acute small bowel obstruction involves laparotomy. The laparoscopic approach has not been favoured due to the presumed increased risk of bowel injury. METHODS: A retrospective review of our experience of laparoscopic management of acute small bowel obstruction was undertaken. Nine patients were identified from 1997 to 2003. The aetiology of obstruction was identified laparoscopically in all cases. Eight cases were caused by bands or local adhesions and one patient had a bezoar. RESULTS: Laparoscopic treatment was successful in 78% of patients including one laparoscopy-assisted procedure. Conversion to laparotomy was performed in two patients, one due to difficult adhesiolysis and one due to iatrogenic bowel injury during adhesiolysis. The mean operating time was 74 minutes. There were no postoperative complications and the mean length of hospital stay was 4.3 days. CONCLUSION: This small series demonstrates that laparoscopy can serve as a good diagnostic tool as well as treatment of acute small bowel obstruction. In an appropriately selected patient, laparoscopic management of small bowel obstruction is a feasible therapeutic approach and appears to convey the benefits of a short postoperative hospital stay, reduced postoperative complications and possibly reduced subsequent adhesion formation.

Alleles at the Nicastrin locus modify presenilin 1- deficiency phenotype.

Presenilin 1 (PS1), presenilin 2, and nicastrin form high molecular weight complexes that are necessary for the endoproteolysis of several type 1 transmembrane proteins, including amyloid precursor protein (APP) and the Notch receptor, by apparently similar mechanisms. The cleavage of the Notch receptor at the "S3-site" releases a C-terminal cytoplasmic fragment (Notch intracellular domain) that acts as the intracellular transduction molecule for Notch activation. Missense mutations in the presenilins cause familial Alzheimer's disease by augmenting the "gamma-secretase" cleavage of APP and overproducing one of the proteolytic derivatives, the Abeta peptide. Null mutations in PS1 inhibit both gamma-secretase cleavage of APP and S3-site cleavage of the Notch receptor. Mice lacking PS1 function have defective Notch signaling and die perinatally with severe skeletal and brain deformities. We report here that a genetic modifier on mouse distal chromosome 1, coinciding with the locus containing Nicastrin, influences presenilin-mediated Notch S3-site cleavage and the resultant Notch phenotype without affecting presenilin-mediated APP gamma-site cleavage. Two missense substitutions of residues conserved among vertebrates have been identified in nicastrin. These results indicate that Notch S3-site cleavage and APP gamma-site cleavage are distinct presenilin-dependent processes and support a functional interaction between nicastrin and presenilins in vertebrates. The dissociation of Notch S3-site and APP gamma-site cleavage activities will facilitate development of gamma-secretase inhibitors for treatment of Alzheimer's disease.

Differential display analysis of presenilin 1-deficient mouse brains.

Missense mutations in presenilin 1 (PS1) gene are the most common cause of early onset familial Alzheimer's disease (FAD). AD pathogenic PS1 mutations result in elevated gamma-secretase cleavage of APP and diminished S3-site cleavage of Notch. We have previously described a PS1-hypomorphic mouse line that could survive postnatally with markedly reduced gamma-secretase cleavage of APP and S3-site cleavage of Notch, resulting in a Notch developmental phenotype similar to PS1-null mice. This model was exploited to identify genes whose expression is altered due to the loss of PS1. A global gene expression study by differential display was performed on whole brains of PS1-hypomorphic mice and their wild type siblings. In total, more than 16,000 bands corresponding to cDNAs were compared between the mutant and wild-type brains. This analysis identified 19 cDNAs showing significantly altered expression resulting from PS1 deficiency. Four of the identified cDNAs corresponded to genes that could be associated with AD or presenilin function. Hypoxia inducible factor 1a (Hif1a), NPRAP (delta-catenin) and cell division cycle 10 (CDC10) showed significantly reduced expression in the PS1-hypomorphic compared to wild-type brains, whereas expression of nucleoside diphosphate kinase sub-unit A (NDPK-A) was markedly elevated in the respective brains. Clarification of the possible role of these genes in AD and the basis for their differential expression induced by PS1-deficiency may provide insight into the disease, presenilin function and consequences of its loss, as well as possible deleterious effects of AD therapeutics aimed at inhibiting PS1.