To gain insight into patterns of presentation, imaging, microbiological aspects, therapy, disease course, and outcome of intracranial complications of sinusitis (ICS), which are challenging conditions with the potential to cause significant morbidity and mortality. We reviewed our experience with ICS in children and adolescents.Design: Consecutive case series with a mean follow-up of 12 months. Setting: Tertiary pediatric referral center. Patients: Consecutive sample of 25 children and adolescents treated for 35 intracranial complications (mean age, 13.2 years [range, 4-18 years]). Interventions: Medical and surgical management. Main Outcome Measures: Survival and temporary and permanent neurologic sequelae.Results: Most patients were adolescents (n=19; 76%) and male (n=19; 76%). Epidural abscess was most common (13 complications), followed by subdural empyema (n=9),

This paper reports the molecular cloning of a novel gene in the mouse that shows structural similarities to the microfibril protein fibrillin and to the latent transforming growth factor-beta (TGF-beta) binding protein (LTBP), a component of the latent TGF-beta complex. The gene was initially isolated during a low stringency polymerase chain reaction screen of a NIH 3T3 cell cDNA library using primers that amplify a human fibrillin-1 epidermal growth factor-like repeat. Three lines of evidence suggest that the mouse gene is a third member of the LTBP gene family, which we designate LTBP-3. First, the deduced polypeptide, which consists of 15 epidermal growth factor-like repeats, 3 TGF binding protein repeats, and 2 proline- and glycine-rich sequences, shows 38.4% identity with LTBP-1 but only 27% identity with fibrillin-1. Second, the gene appears to be co-expressed in developing mouse tissues with TGF-beta. Third, immunoprecipitation studies using mouse preosteoblast MC3T3-E1 cells and a specific anti-peptide polyclonal antiserum reveal that the mouse polypeptide forms a complex with the TGF-beta 1 precursor. Finally, we note that the LTBP-3 gene was recently localized to a distinct genetic locus (Li, X., Yin, W., Perez-Jurado, L., Bonadio, J., and Francke, U. (1995) Mamm. Genome 6, 42-45). Identification of a third binding protein provides further insight into a mechanism by which latent TGF-beta complexes can be targeted to connective tissue matrices and cells.

Cochlear nerve deficiency is a common cause of unilateral SNHL, particularly in congenital unilateral deafness. Width of the BCNC effectively predicts CND, a finding useful when only computed tomography imaging is available. In an ear with CND, hearing can be expected to remain stable over time. Diagnosis should prompt evaluation by an ophthalmologist.

The workup of children with hearing loss can be guided by the recommendations provided herein.

This study is the first to demonstrate that macrophage migration inhibitory factor (MIF), an immune system ‘inflammatory’ cytokine that is released by the developing otocyst, plays a role in regulating early innervation of the mouse and chick inner ear. We demonstrate that MIF is a major bioactive component of the previously uncharacterized otocyst-derived factor, which directs initial neurite outgrowth from the statoacoustic ganglion (SAG) to the developing inner ear. Recombinant MIF acts as a neurotrophin in promoting both SAG directional neurite outgrowth and neuronal survival and is expressed in both the developing and mature inner ear of chick and mouse. A MIF receptor, CD74, is found on both embryonic SAG neurons and adult mouse spiral ganglion neurons. Mif knockout mice are hearing impaired and demonstrate altered innervation to the organ of Corti, as well as fewer sensory hair cells. Furthermore, mouse embryonic stem cells become neuron-like when exposed to picomolar levels of MIF, suggesting the general importance of this cytokine in neural development.

No abstract

Normal growth and development of the skeleton require the presence of viable, actively contracting skeletal muscle throughout the fetal period. A chick embryo model of midgestation chemical paralysis and secondary muscle atrophy was used to test the hypothesis that functioning muscle stimulates the growth of long bones by influencing the proliferation, differentiation, and hypertrophy of chondrocytes in cartilage of the epiphysis and growth plate. Paralysis did not alter the overall developmental stage of the long bone or the organization of the growth plate. Compared with controls, however, uptake of bromodeoxyuridine in the paralyzed chick was reduced by 27-55% in the chondroepiphysis and uppermost zone of the tibial growth plate, indicating reduced proliferation of chondrocytes. A specific reduction in the size of the proliferative zone and a reduced number of proliferating cells were also observed. By contrast, in the second, post-proliferative zone of the growth plate, the height of the zone was unchanged and its area was only slightly reduced compared with controls. Finally, median hypertrophic cell profile area, a measure of cell size, was not significantly affected by paralysis, although frequency analysis revealed modest numerical reductions in the population of the largest hypertrophic chondrocytes in the paralyzed group. These data suggest that the role of functioning fetal muscle in maintaining proper skeletal growth may be mediated primarily through specific stimulation of the recruitment or proliferation of immature chondrocytes, or of both.

Summary Alternative splicing contributes to gene expression dynamics in many tissues, yet its role in auditory development remains unclear. We performed whole exome sequencing in individuals with sensorineural hearing loss (SNHL) and identified pathogenic mutations in Epithelial Splicing Regulatory Protein 1 (ESRP1). Patient derived iPSCs showed alternative splicing defects that were restored upon repair of an ESRP1 mutant allele. To determine how ESRP1 mutations cause hearing loss we evaluated Esrp1−/− mouse embryos and uncovered alterations in cochlear morphogenesis, auditory hair cell differentiation and cell fate specification. Transcriptome analysis revealed impaired expression and splicing of genes with essential roles in cochlea development and auditory function. Aberrant splicing of Fgfr2 blocked stria vascularis formation due to erroneous ligand usage, which was corrected by reducing Fgf9 gene dosage. These findings implicate mutations in ESRP1 as a cause of SNHL and demonstrate the complex interplay between alternative splicing, inner ear development, and auditory function.