Insights Into Elevated Distortion Product Otoacoustic Emissions In Sickle Cell Disease: Comparisons of Hydroxyurea-treated and Non-treated Young Children

Distortion product otoacoustic emissions (DPOAEs) were examined in 15 normal- hearing African-American children between the ages of 6 and 14 years with homozygous sickle cell disease (SCD), who were on a regimen of hydroxyurea (HDU), a drug that reduces inflammatory processes and symptoms of SCD; a matched group of 15 African- American children with homozygous SCD not on HDU; and 15 African-American children with normal hemoglobin. DPOAEs were evoked by 13 primary tone pairs with f2 frequencies ranging from 1000 to 4500 Hz. Increased DPOAE amplitudes, believed to be a precursor of eventual hearing loss, were evident in children with SCD who were not receiving HDU. Those taking HDU had DPOAE amplitudes similar to normal controls. These findings suggest that HDU, in addition to reducing symptoms of SCD, may play a role in inhibiting or preventing cochlear pathology and hearing loss in individuals with SCD. Key Words: distortion product otoacoustic emissions; sickle cell disease; hydroxyurea Abbreviations: ABR = auditory brainstem response; DPOAE = distortion product otoacoustic emission; HDU = hydroxyurea; HbSS = homozygous sickle cell disease; ICAM = intercellular adhesion molecule; M = mean; OAE = otoacoustic emission; p = probability; PECAM = platelet-endothelial cell adhesion molecule SCD = sickle cell disease; SD = standard deviation of the mean; SOAE = spontaneous otoacoustic emission; TEOAE = transient evoked otoacoustic emission; VCAM = vascular cell adhesion molecule

Ponatinib promotes a G1 cell-cycle arrest of merlin/NF2-deficient human schwann cells

Neurofibromatosis type 2 (NF2) is a genetic syndrome that predisposes individuals to multiple benign tumors of the central and peripheral nervous systems, including vestibular schwannomas. Currently, there are no FDA approved drug therapies for NF2. Loss of function of merlin encoded by the NF2 tumor suppressor gene leads to activation of multiple mitogenic signaling cascades, including platelet-derived growth factor receptor (PDGFR) and SRC in Schwann cells. The goal of this study was to determine whether ponatinib, an FDA-approved ABL/SRC inhibitor, reduced proliferation and/or survival of merlin-deficient human Schwann cells (HSC). Merlin-deficient HSC had higher levels of phosphorylated PDGFRα/β, and SRC than merlin-expressing HSC. A similar phosphorylation pattern was observed in phospho-protein arrays of human vestibular schwannoma samples compared to normal HSC. Ponatinib reduced merlin-deficient HSC viability in a dose-dependent manner by decreasing phosphorylation of PDGFRα/β, AKT, p70S6K, MEK1/2, ERK1/2 and STAT3. These changes were associated with decreased cyclin D1 and increased p27Kip1levels, leading to a G1 cell-cycle arrest as assessed by Western blotting and flow cytometry. Ponatinib did not modulate ABL, SRC, focal adhesion kinase (FAK), or paxillin phosphorylation levels. These results suggest that ponatinib is a potential therapeutic agent for NF2-associated schwannomas and warrants further in vivo investigation

Long-Term Efficacy of Endolymphatic Sac Surgery for Vertigo in Meniere's Disease

The long-term efficacy of endolymphatic sac procedures for control of vertigo in Melnere's disease has been controversial. We evaluated results of sac shunt surgery for 234 patients having at least 10 years followup (mean, 13.5 years). All patients had persistent vestibular symptoms despite medical therapy. All underwent endolymphatic subarachnoid shunt as their original operation. Data were collected by chart review and questionnaire regarding: (1) the number of additional surgical procedures to control vertigo, (2) remaining dizziness, and (3) level of disability. One hundred forty-seven of the patients (63%) did not undergo any further surgery to control vertigo, and an additional 17% had only revisions of the endolymphatic sac shunt. Thus, 80% never required a destructive procedure. Long-term effectiveness of surgery in regard to dizziness and disability was determined from the questionnaire. Of the 147 patients with only the original sac shunt surgery, 93% reported no dizziness or mild to no disability. Of the group who underwent only revisions of the original shunt, 96% stated they had no more dizziness or mild to no disability. We conclude that endolymphatic sac shunt operations are effective as Initial surgical procedures for long-term control of disabling vertigo of Meniere's disease

Surgical techniques for cochlear implantation of the malformed inner ear

The objective was to describe surgical techniques helpful in implanting children with inner ear malformations. This was a retrospective chart review and description of surgical techniques in the setting of a tertiary referral center. The study population was composed of 10 children with inner ear deformities who received 22-channel implants. The primary surgical challenges encountered in these procedures include complete electrode insertion, cerebrospinal fluid gusher, identification of cochleostomy site in the absence of the round window and aberrant facial nerve, and fixation and stabilization of the electrode. The techniques described allow safe and effective insertion of multichannel electrodes in patients with inner ear malformations