Late Onset Hearing Loss in Very Low Birth Weight Infants.

Objective: To determine the incidence of late onset hearing loss and associated risk factors in very low birth weight (VLBW) infants. Study Design: Retrospective study (2003-2015) of post-discharge hearing outcomes and risk factors in the VLBW infant population, before and after the institution of a standardized follow-up program. Results: Late onset hearing loss increased from 2.9 per 100 VLBW infants to 7.8 per 100 after instituting a monitoring protocol. The follow-up compliance rate nearly doubled. Both infants with late-onset sensorineural hearing loss and those with a conductive component were identified. The rate of conductive loss detection increased seven-fold. Conclusion: The institution of a standardized hearing follow-up program significantly increased the detection of late onset hearing loss in VLBW infants. A significant proportion of those with late onset hearing loss had a conductive component. Without identification and treatment, even conductive losses may negatively impact speech and language development.

Use of Fish Oil-Based Lipid Emulsions in Infants With Intestinal Failure-Associated Liver Disease: A Case Series.

The use of fish oil-based lipid emulsions (FOLE) in the treatment of intestinal failure-associated liver disease (IFALD) remains investigational. Additional evidence for safety and efficacy, particularly in the neonatal and pediatric populations, is needed. Retrospective chart review was conducted on 10 infants with short bowel syndrome who received FOLE for IFALD. Direct bilirubin concentrations normalized in surviving subjects within 4.1 to 22.7 weeks of starting treatment. Although earlier initiation of FOLE was not associated with more rapid normalization of direct bilirubin concentrations, it trended toward a significant correlation with reduced length of hospital stay (P = .058). The reduction in direct bilirubin levels and transition from parenteral to enteral feeding were statistically significant within 6 weeks of initiating the FOLE. Subjects did not have impaired growth and did not develop an essential fatty acid deficiency. These infants were discharged from the hospital 7.9 to 42.3 weeks after starting FOLE treatment, and 2 infants had transitioned completely off parenteral nutrition at discharge. In this study, FOLE appeared to be a safe and effective treatment for IFALD in infants with short bowel syndrome. Future studies are necessary to determine whether FOLE can help to prevent or shorten the duration of cholestasis.

Na-K-2Cl cotransporter inhibition impairs human lung cellular proliferation.

The widespread presence of the Na-K-2Cl (NKCC) cotransporter protein suggests that chronic administration of inhibitors may result in adverse effects. Inhibition of the NKCC cotransporter by loop diuretics is felt to underlie the diuretic and the pulmonary smooth muscle relaxant effects of this drug class. However, the fundamental regulation of salt and water movement by this cotransporter suggests that it may also mediate cell volume changes occurring during cell cycle progression. Thus we hypothesized that NKCC cotransporter inhibition by loop diuretics would decrease cellular proliferation. Normal human bronchial smooth muscle cells (BSMC) showed a significant concentration-dependent decrease in cell counts after 7 days of exposure to both bumetanide (n=5-10) and furosemide (n=6-16) compared with controls. Proliferation was similarly inhibited in normal human lung fibroblasts (n=5-9). To determine whether this was due to loss of cells, we performed apoptosis assays on BSMC. Both annexin V-propidium iodide staining (n=5-10) and single cell gel electrophoresis assays (n=4) were negative for necrosis and apoptosis in BSMC exposed to 10 microM bumetanide. Subsequent analysis of the cell cycle by flow cytometry showed that bumetanide-exposed BSMC were delayed in G1 phase compared with controls (n=4-8). This is the first evidence for loop diuretic inhibition of airway smooth muscle cell proliferation. NKCC cotransporter inhibition impeded G1-S phase transition without facilitating cell death. Thus although inhibition by loop diuretics relaxes airway smooth muscle, the NKCC cotransporter may have a more important role in cell proliferation regulation.

Immunolocalization of a Na-K-2Cl cotransporter in human tracheobronchial smooth muscle.

Inhibition of the Na-K-2Cl (NKCC) cotransporter by loop diuretics is associated with airway relaxation, but there has been no direct evidence for the expression of this protein in airway smooth muscle. Thus we hypothesized that a NKCC cotransporter is present and functional in airway smooth muscle cells. Monoclonal and polyclonal antibodies were used first to demonstrate the presence of a NKCC cotransporter protein in isolated human fetal trachea and normal human bronchial smooth muscle cells (BSMC) by Western blotting. The cotransporter protein was then localized by immunohistochemical staining to airway smooth muscle cells in culture and in situ. The localization was confirmed by indirect immunofluorescence and laser confocal microscopy in the BSMC. Cotransporter function in BSMC was also confirmed in vitro by bumetanide-mediated inhibition of rubidium uptake. Our present findings thus document the presence of a functional NKCC cotransporter in human airway smooth muscle, providing a basis for defining the role of this ion cotransporter in airway smooth muscle function.