Truncating mutation in the nitric oxide synthase 1 gene is associated with infantile achalasia.

Nitric oxide is thought to have a role in the pathogenesis of achalasia. We performed a genetic analysis of 2 siblings with infant-onset achalasia. Exome analysis revealed that they were homozygous for a premature stop codon in the gene encoding nitric oxide synthase 1. Kinetic analyses and molecular modeling showed that the truncated protein product has defects in folding, nitric oxide production, and binding of cofactors. Heller myotomy had no effect in these patients, but sildenafil therapy increased their ability to drink. The finding recapitulates the previously reported phenotype of nitric oxide synthase 1-deficient mice, which have achalasia. Nitric oxide signaling appears to be involved in the pathogenesis of achalasia in humans.

Amyand's hernia with perforated appendicitis in a premature infant.

We present a case of Amyand's hernia with perforated appendicitis in a premature infant. The favorable outcome compared to perforated abdominal appendicitis is discussed. Despite its rarity, this diagnosis should be considered in the differential diagnosis of a scrotal mass in premature infants.

Comparison of pediatric appendectomy outcomes between pediatric surgeons and general surgery residents.

BACKGROUND: Appendectomy is the most common urgent procedure in children, and surgical outcomes may be affected by the surgeon's experience. This study's aim is to compare appendectomy outcomes performed by pediatric surgeons (PSs) and general surgery residents (GSRs). MATERIALS AND METHODS: A retrospective review of all patients younger than 16y treated for appendicitis at two different campuses of the same institution during the years 2008-2009 was performed. Appendectomies were performed by PS in one campus and GSR in the other. Primary end points included postoperative morbidity and hospital length of stay. RESULTS: During the study period, 246 (61%) patients were operated by senior GSR (postgraduate year 5-7) versus 157 (39%) patients by PS. There was no significant difference in patients' characteristics at presentation to the emergency room and the rate of appendeceal perforation (11% versus 15%, P=0.32), and noninfectious appendicitis (5% versus 5% P=0.78) also was similar. Laparoscopic surgery was performed more commonly by GSR (16% versus 9%, P=0.02) with shorter operating time (54±1.5 versus 60±2.1, P=0.01). Interestingly, the emergency room to operating room time was shorter for GSR group (419±14 versus 529±24min, P<0.001). The hospital length of stay was shorter for the GSR group (4.0±0.2 versus 4.5±0.2, P=0.03), and broad-spectrum antibiotics were used less commonly (20% versus 53%, P<0.0001) and so was home antibiotics continuation (13% versus 30%, P<0.0001). Nevertheless, postoperative complication rate was similar (5% versus 7%, P=0.29) and so was the rate of readmissions (2% versus 5%, P=0.52). CONCLUSIONS: The results of this study suggest that the presence of a PS does not affect the outcomes of appendectomies.

Decreased density of ganglia and neurons in the myenteric plexus of familial dysautonomia patients.

BACKGROUND: Familial dysautonomia (FD) is a hereditary disease of the autonomic and sensory nervous system. A prominent manifestation of FD is gastrointestinal dyscoordination, which contributes to the morbidity and mortality in FD. AIM: As the myenteric plexus is an essential factor in gastrointestinal motility control, we compared its morphology in appendices of FD patients and controls. METHODS: Appendices from FD patients (N=19) were obtained during surgery of fundoplication and gastrostomy; normal appendices (N=17) were obtained from patients suspected to suffer from acute appendicitis, in whom, however, the appendix was found to be normal. Specimens were stained histochemically for NADPH diaphorase (NADPH-d) and in a blinded manner examined under a light microscope for seven morphologic parameters: ganglionic density, neuronal density, ganglionic area, number of stained neurons per ganglion, nerve bundle width, ratio between nervous tissue area and total area, and neuronal area. RESULTS: Ganglionic density was 10.13 per mm(2) in controls versus 5.01 per mm(2) in FD (p<0.05). Neuronal density was 70.12 per mm(2) in controls, compared with 22.09 per mm(2) in FD (p<0.01). The other parameters were not different between the two groups. CONCLUSION: Densities of myenteric ganglia and neurons of FD patients were significantly lower than in controls. This deficiency may contribute to the pathogenesis of FD gastroenteropathy.