No abstract

No abstract

GERD (gastroesophageal reflux disease) is a frequent consideration in ICU neonates. We tested the hypothesis that symptoms in GERD are dependent on the spatio-temporal and physico-chemical characteristics of reflux events by evaluating the symptom sensitivity index (SSI) and symptom index (SI) in relation to the refluxate characteristics. Thirty symptomatic neonates (30.7±0.8 wk gestation) were evaluated using manometry and pH-Impedance methods. During 704.3 hr of recordings, 2,063 GER (gastroesophageal reflux) were observed; 54% of the GER were associated with symptoms. Defined by physical characteristics, there were 51.3% liquid, 29.1% gas, and 19.6% mixed GER. Defined by chemical characteristics, there were 48.5% acid- and 51.5% non-acid GER. Defined by most proximal extent, 79.2% were supra-UES (upper esophageal sphincter), 20.8% were infra-UES. Higher SSI was noted with pH-only events (P<0.0001 vs. pH-Impedance events). Higher SI was noted with movement symptoms (vs. sensory, P=0.04). In a subset analysis, the frequencies of GER events, acid clearance time, and SSI were all greater in chronic lung disease vs. none (P<0.001). In conclusion, clinical significance of symptoms as measured by SSI and SI and characterization of spatial-temporal-physical-chemical nature of GER events as defined by pH-impedance methods clarifies the definition of GERD.

No abstract

No abstract

Background Feeding difficulties and gastroesophageal reflux (GER) are common problems in neonates. The authors hypothesize that GER could be influenced by feeding mechanics by evaluating the effects of feeding volumes, feeding durations, feeding flow rates, and caloric density on the chemical composition and clearance of GER in dysphagic neonates. Methods Symptomatic dysphagic neonates (n = 35) underwent evaluation for suspected GER using pH-impedance methods. Results The proportions of acid and nonacid GER were different during the first, second, and third postprandial hours (P < .0001). Prolonged feeding duration was significantly associated with decreased total, nonacid GER and BCT (P < .03). Significant positive correlations (P < .05) were detected between feeding flow rate vs frequency of total, nonacid GER and BCT. Significant positive correlation (P = .002) was noted between feeding volume and BCT. BCT decreased with each hourly interval (analysis of variance [ANOVA] P < .05); however, ACT increased with each hourly interval (ANOVA P = .05). Comparison between BCT and ACT at each postprandial hour is remarkable for longer ACT during the second and third hours after the initiation of feed (P ≤ .001). No significant correlation was noted between the milk types (breast milk or formula) or caloric density with regard to the GER characteristics. Oral-fed infants had more GER events than gavage-fed infants. Conclusions Prolonged feeding durations and slower flow rates are associated with decreased frequency of GER. Modification of feeding duration and flow rate can be a useful adjunct to ameliorate GER in dysphagic neonates.

Regulated intestinal stem cell proliferation and differentiation are required for normal intestinal homeostasis and repair after injury. The Notch signaling pathway plays fundamental roles in the intestinal epithelium. Despite the fact that Notch signaling maintains intestinal stem cells in a proliferative state and promotes absorptive cell differentiation in most species, it remains largely unclear how Notch signaling itself is precisely controlled during intestinal homeostasis. We characterized the intestinal phenotypes of brom bones, a zebrafish mutant carrying a nonsense mutation in hnRNP I. We found that the brom bones mutant displays a number of intestinal defects, including compromised secretory goblet cell differentiation, hyperproliferation, and enhanced apoptosis. These phenotypes are accompanied by a markedly elevated Notch signaling activity in the intestinal epithelium. When overexpressed, hnRNP I destabilizes the Notch intracellular domain (NICD) and inhibits Notch signaling. This activity of hnRNP I is conserved from zebrafish to human. In addition, our biochemistry experiments demonstrate that the effect of hnRNP I on NICD turnover requires the C-terminal portion of the RAM domain of NICD. Our results demonstrate that hnRNP I is an evolutionarily conserved Notch inhibitor and plays an essential role in intestinal homeostasis.

No abstract