The dominant efferent innervation of the cochlea terminates on outer hair cells (OHCs), with acetylcholine (ACh) being its principal neurotransmitter. OHCs respond with a somatic shape change to alterations in their membrane potential, and this electromotile response is believed to provide mechanical feedback to the basilar membrane. We examine the effects of ACh on electromotile responses in isolated OHCs and attempt to deduce the mechanism of ACh action. Axial electromotile amplitude and cell compliance increase in the presence of the ligand. This response occurs with a significantly greater latency than membrane current and potential changes attributable to ACh and is contemporaneous with Ca 2ϩ release from intracellular stores. It is likely that increased axial compliance largely accounts for the increase in motility. The mechanical responses are probably related to a recently demonstrated slow efferent effect. The implications of the present findings related to commonly assumed efferent behavior in vivo are considered.

Cyclooxygenase-2 (COX2) is a primary inflammatory mediator that converts arachidonic acid into precursors of vasoactive prostaglandins, producing reactive oxygen species in the process. Under normal conditions COX2 is not detectable, except at low abundance in the brain. This study demonstrates a distinctive pattern of COX2 increases in the brain over time following traumatic brain injury (TBI). Quantitative lysate ribonuclease protection assays indicate acute and sustained increases in COX2 mRNA in two rat models of TBI. In the lateral fluid percussion model, COX2 mRNA is significantly elevated (>twofold, p < 0.05, Dunnett) at 1 day postinjury in the injured cortex and bilaterally in the hippocampus, compared to sham-injured controls. In the lateral cortical impact model (LCI), COX2 mRNA peaks around 6 h postinjury in the ipsilateral cerebral cortex (fivefold induction, p < 0.05, Dunnett) and in the ipsilateral and contralateral hippocampus (two-and sixfold induction, respectively, p < 0.05, Dunnett). Increases are sustained out to 3 days postinjury in the injured cortex in both models. Further analyses use the LCI model to evaluate COX2 induction. Immunoblot analyses confirm increased levels of COX2 protein in the cortex and hippocampus. Profound increases in COX2 protein are observed in the cortex at 1-3 days, that return to sham levels by 7 days postinjury (p < 0.05, Dunnett). The cellular pattern of COX2 induction following TBI has been characterized using immunohistochemistry. COX2-immunoreactivity (-ir) rises acutely (cell numbers and intensity) and remains elevated for several days following TBI. Increases in COX2-ir colocalize with neurons (MAP2-ir) and glia (GFAP-ir). Increases in COX2-ir are observed in cerebral cortex and hippocampus, ipsilateral and contralateral to injury as early as 2 h postinjury. Neurons in the ipsilateral parietal, perirhinal and piriform cortex become intensely COX2-ir from 2 h to at least 3 days postinjury. In agreement with the mRNA and immunoblot results, COX2-ir appears greatest in the contralateral hippocampus. Hippocampal COX2-ir progresses from the pyramidal cell layer of the CA1 and CA2 region at 2 h, to the CA3 pyramidal cells and dentate polymorphic and granule cell layers by 24 h postinjury. These increases are distinct from those observed following inflammatory challenge, and correspond to brain areas previously identified with the neurological and cognitive deficits associated with TBI. While COX2 induction following TBI may result in selective beneficial responses, chronic COX2 production may contribute to free radical mediated cellular damage, vascular dysfunction, and alterations in cellular metabolism. These may cause secondary injuries to the brain that promote neuropathology and worsen behavioral outcome.

Introduction: Postoperative delirium is associated with opioid use in the elderly and is a common complication of geriatric hip fractures, with reported incidences from 16% to 70%. Intravenous (IV) acetaminophen is a safe and efficacious medication in elderly patients and has been shown to reduce use of opioids after hip fracture. At our institution, IV acetaminophen was implemented for the first 24 hours postoperatively as part of a multimodal pain control regimen for geriatric hip fracture patients. Methods: A retrospective review of 123 hip fragility fracture patients older than 60 years from January 2016 to December 2016 was performed. Delirium was identified using a validated chart–based review tool. The rate of delirium, as well as length of stay, pain scores, opioid administration, need for one-to-one supervision, and readmissions were analyzed. Results: Sixty-five patients (52.8%) received IV acetaminophen during this period. No notable differences were found in baseline characteristics between groups. Ten of 65 patients receiving IV acetaminophen postoperatively experienced delirium compared with 19 of 58 who did not receive the medication (15.4% versus 32.8%, P = 0.024). The IV acetaminophen group also required fewer doses of IV opioids on postoperative day 1 (0.37 versus 1.19 doses, P = 0.008), were less likely to require one-to-one supervision (9.2% versus 24.1%, P = 0.025), and had shorter lengths of hospital stay (6.37 versus 8.47 days, P = 0.037). Readmission rates and discharge dispositions did not vary with significance between the two groups. Conclusion: The inclusion of IV acetaminophen as part of a multimodal pain regimen led to fewer episodes of delirium in this study. The reduced use of opioids immediately after surgery may have been a large factor in this outcome. Lower delirium rates may reduce the utilization of inpatient resources for direct patient supervision and provide for shorter hospital stays.

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