Effect of Cochlear Implantation on the Endocochlear Potential and Stria Vascularis.

Hypothesis: Animals with cochlear implantation-induced hearing loss will have a lower endocochlear potential (EP) and decreased strial vascular density.

Background: The cause of residual hearing loss following cochlear implantation remains poorly understood. Recent work from our lab has shown a correlation between vascular changes in the cochlear lateral wall and postimplantation hearing loss, suggesting a role of the stria vascularis and EP.

Stapes Surgery Outcomes in Patients With Concurrent Otosclerosis and Superior Semicircular Canal Dehiscence.

Objective: To review outcomes of stapes surgery in patients with concurrent otosclerosis and superior semicircular canal dehiscence.

Study Design: Retrospective case series.

Setting: Tertiary referral center.

The 'totality-of-the-evidence' approach in the development of PF-06438179/GP1111, an infliximab biosimilar, and in support of its use in all indications of the reference product.

The 'totality-of-the-evidence' biosimilarity concept requires that sufficient structural, functional, nonclinical, and clinical data are acquired in a stepwise manner, to demonstrate that no clinically meaningful differences in quality, safety, or efficacy are observed compared with the reference product. We describe the totality of the evidence for PF-06438179/GP1111 (PF-SZ-IFX; IXIFI™ [infliximab-qbtx]/Zessly®) that supported its approval as an infliximab (IFX) biosimilar for all eligible indications of reference IFX (ref-IFX; Remicade®) in Europe and in the US. Analytical similarity involving assays capable of distinguishing structural or functional differences between PF-SZ-IFX and ref-IFX formed a foundation for the biosimilarity exercise.

A randomized study comparing the pharmacokinetics of the potential biosimilar PF-06438179/GP1111 with Remicade® (infliximab) in healthy subjects (REFLECTIONS B537-01).

Background: To demonstrate pharmacokinetic (PK) similarity of PF-06438179/GP1111, a potential biosimilar to Remicade®, to Remicade® sourced from European Union (infliximab-EU) and United States (infliximab-US), and of infliximab-EU to infliximab-US.

Methods: In this phase I, parallel-group, three-arm trial, healthy adult subjects were randomized to receive a single 10-mg/kg intravenous infusion of PF-06438179/GP1111, infliximab-EU, or infliximab-US. PK, and safety and immunogenicity evaluations were performed over 8 and 12 weeks, respectively.

Small bowel obstruction after transoral robotic surgery.

Background: Head and neck surgery is not often considered a risk factor for intestinal ileus and small bowel obstruction. However, many of these patients may have had prior abdominal surgery, a known risk factor for small bowel obstruction, and may be at risk for bowel obstruction after a surgical procedure of the head and neck.

Methods: We present a case describing a patient who, after undergoing transoral robotic surgery, experienced delayed postoperative ileus and eventual small bowel obstruction requiring exploratory laparotomy and bowel resection.

Development of biosimilars.

Objective: To provide an overview of the underlying scientific principles and standards for developing a biosimilar product.

Methods: An Internet-based literature search through June 2015 was performed for information related to biosimilar manufacturing and development, including a review of regulatory guidelines and requirements.

Results: Biologics, both biosimilars and their corresponding reference products, are complex molecules produced by biotechnology in living systems.

Intraoperative round window electrocochleography and speech perception outcomes in pediatric cochlear implant recipients.

Objectives: The goal was to measure the magnitude of cochlear responses to sound in pediatric cochlear implant recipients at the time of implantation and to correlate this magnitude with subsequent speech perception outcomes.

Design: A longitudinal cohort study of pediatric cochlear implant recipients was undertaken. Intraoperative electrocochleographic (ECoG) recordings were obtained from the round window in response to a frequency series at 90 dB nHL in 77 children totaling 89 ears (12 were second side surgeries) just before device insertion.

Round window electrocochleography and speech perception outcomes in adult cochlear implant subjects: comparison with audiometric and biographical information.

Hypothesis: Intraoperative round window (RW) electrocochleography (ECoG) can help predict speech perception outcomes in adult cochlear implant (CI) recipients.

Background: Speech perception outcomes using CIs are highly variable. Recent data demonstrated that intraoperative ECoG could account for nearly half the variance in postoperative word scores.

Triggering a cell shape change by exploiting preexisting actomyosin contractions.

Apical constriction changes cell shapes, driving critical morphogenetic events, including gastrulation in diverse organisms and neural tube closure in vertebrates. Apical constriction is thought to be triggered by contraction of apical actomyosin networks. We found that apical actomyosin contractions began before cell shape changes in both Caenorhabitis elegans and Drosophila.

The measurement of extravascular lung density with SPECT imaging and its relationship with ventilatory abnormalities in patients with congestive heart failure.

Background: Patients with congestive heart failure (CHF) have increased ventilatory equivalent for carbon dioxide (Ve/VCO(2)), which may contribute to the symptom of exercise-induced hyperpnea. We have developed a technique in which simultaneous blood volume single photon emission computed tomography imaging and transmission tomography are used to measure extravascular lung density (ELD). We investigated the correlation between Ve/VCO(2) and ELD in patients with CHF.

Parent and neutral loss monitoring on a quadrupole ion trap mass spectrometer: screening of acylcarnitines in complex mixtures.

A novel and practical technique for performing both parent and neutral loss (P&NL) monitoring experiments on a quadrupole ion trap mass spectrometer is presented. This technique is capable of performing scans analogous to the parent and neutral loss scans routinely applied on tandem-in-space instruments and allows for the screening of a sample to detect analytes of a specific compound class on a chromatographic time-scale. Acylcarnitines were chosen as the model compound class to demonstrate the analytical utility of P&NL monitoring because of their amenability to electrospray ionization (ESI), their unique and informative MS/MS fragmentation pattern, and their importance in biological functions.

Influence of charge state on product ion mass spectra and the determination of 4S/6S sulfation sequence of chondroitin sulfate oligosaccharides.

Electrospray ionization-Fourier transform ion cyclotron resonance tandem mass spectrometry is used to study the influence of charge state on the product ion spectra of chondroitin sulfate oligosaccharides for determination of the sulfate position on N-acetylgalactosamine residues. Sustained off-resonance irradiation collision-induced dissociation and infrared multiphoton dissociation are investigated for tandem mass spectrometry of chondroitin sulfate. Product ion spectra were obtained for ions of varying charge states from (4,5)-unsaturated (delta-unsaturated), reduced delta-unsaturated, and saturated oligosaccharides from chondroitin sulfate A and chondroitin sulfate C, separately.

Effects of fragile ions on mass resolution and on isolation for tandem mass spectrometry in the quadrupole ion trap mass spectrometer.

In the quadrupole ion trap, it has been noted that factors other than an ion's mass and charge may affect its measured m/z, resulting in compound-dependent, or "chemical", mass shifts. We propose that ions can exhibit a chemical mass shift because they are "fragile" and may fragment during the application of resonance ejection during mass analysis; these effects were studied using ions that include protonated, deprotonated, and adduct ions of explosives, acylcarnitines, and macrolide antibiotics. Fragile ions affect mass resolution by causing broader peaks than nonfragile ions, especially at slower scan speeds, as the result of the application of resonance ejection.