Studies on bilateral cochlear implants at the University of Wisconsin's Binaural Hearing and Speech Laboratory

This report highlights research projects relevant to binaural and spatial hearing in adults and children. In the past decade we have made progress in understanding the impact of bilateral cochlear implants (BiCIs) on performance in adults and children. However, BiCI users typically do not perform as well as normal hearing (NH) listeners. In this article we describe the benefits from BiCIs compared with a single cochlear implant (CI), focusing on measures of spatial hearing and speech understanding in noise. We highlight the fact that in BiCI listening the devices in the two ears are not coordinated; thus binaural spatial cues that are available to NH listeners are not available to BiCI users. Through the use of research processors that carefully control the stimulus delivered to each electrode in each ear, we are able to preserve binaural cues and deliver them with fidelity to BiCI users. Results from those studies are discussed as well, with a focus on the effect of age at onset of deafness and plasticity of binaural sensitivity. Our work with children has expanded both in number of subjects tested and age range included. We have now tested dozens of children ranging in age from 2 to 14 yr. Our findings suggest that spatial hearing abilities emerge with bilateral experience. While we originally focused on studying performance in free field, where real world listening experiments are conducted, more recently we have begun to conduct studies under carefully controlled binaural stimulation conditions with children as well. We have also studied language acquisition and speech perception and production in young CI users. Finally, a running theme of this research program is the systematic investigation of the numerous factors that contribute to spatial and binaural hearing in BiCI users. By using CI simulations (with vocoders) and studying NH listeners under degraded listening conditions, we are able to tease apart limitations due to the hardware/software of the CI systems from limitations due to neural pathology.     

The effects of high dose and highly fractionated radiation on distraction osteogenesis in the murine mandible

ABSTRACT: The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague--Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction.     

Relationship between cytokine gene single nucleotide polymorphisms and symptom burden and quality of life in lung cancer survivors

BACKGROUND:

Previous research has demonstrated that many lung cancer survivors report difficulties with symptom control and experience a poor quality of life (QOL). Although recent studies have suggested a relationship of single nucleotide polymorphisms (SNPs) in several cytokine genes with cancer susceptibility and prognosis, associations with symptom burden and QOL have not been examined. The current study was conducted to identify SNPs related to symptom burden and QOL outcomes in lung cancer survivors.

METHODS:

All participants were enrolled in the Mayo Clinic Lung Cancer Cohort following diagnosis of lung cancer. A total of 1149 Caucasian lung cancer survivors completed questionnaires and had genetic samples available. The main outcome measures were symptom burden as measured by the Lung Cancer Symptom Scale and health‐related QOL as measured by the Short‐Form General Health Survey.

RESULTS:

Twenty‐one SNPs in cytokine genes were associated with symptom burden and QOL outcomes. Our results suggested both specificity and consistency of cytokine gene SNPs in predicting outcomes.

CONCLUSIONS:

These results provide support for genetic predisposition to QOL and symptom burden and may aid in identification of lung cancer survivors at high risk for symptom management and QOL difficulties. Cancer 2010. © 2010 American Cancer Society.     

Relationship of Optimism–Pessimism and Health-Related Quality of Life in Breast Cancer Survivors

ABSTRACT

Few studies have investigated the influence of optimism–pessimism in breast cancer survivors. This study used a retrospective design with 268 adult women who completed the Minnesota Multiphasic Personality Inventory (MMPI) as part of their medical care approximately 10 years prior to their breast cancer diagnosis and Medical Outcome Study Short-Form General Health Survey (SF-36 or SF-12), on average, 8 years after diagnosis. MMPI pessimism scores were divided into quartiles, and t tests were used to determine differences between those highest and lowest in pessimism on health-related quality-of-life (QOL) measures, demographics, and disease status. The mean age at diagnosis of breast cancer was 63 years, and 74% had early-stage breast cancer. Patients age 65 years and older were significantly lower on physical health–related QOL scales. There were no significant differences in health-related QOL scores by stage of disease. Patients with a pessimistic explanatory style were significantly lower on all of the health-related QOL scores, compared to those with a nonpessimistic style. Breast cancer survivors who exhibit a pessimistic explanatory style report lower health-related QOL for years after receiving a cancer diagnosis, compared to nonpessimistic women.     

Human O6‐methylguanine‐DNA methyltransferase containing C145A does not prevent hepatocellular carcinoma in C3HeB/FeJ transgenic mice

The prevalence of hepatocellular carcinoma (HCC) was diminished from 60% to 18% at 15 months of age in C3HeB/FeJ male transgenic mice expressing hMGMT in our previous studies. To directly test if the methyltransferase activity is required for diminished tumor prevalence, two separate lines of transgenic mice bearing an enzymatically inactive form of hMGMT were used. In these lines, cysteine 145 was substituted with alanine (C145A). Expression of the hMGMT C145A transgene in liver was demonstrated by Northern blots and Western blots. Immunohistochemistry revealed predominantly nuclear localization of the hMGMT C145A protein. hMGMT C145A transgenic mice were crossed with lacI transgenic mice to assess mutant frequencies in the presence of the mutant protein. Mutant frequencies were similar among livers of lacI × hMGMT C145A bi‐transgenic mice and lacI × wild‐type (WT) mice. DNA sequence analysis of recovered lacI mutants revealed similar mutation spectra for hMGMT C145A and WT mice. The prevalence of HCC was also similar for the two tested lines of hMGMT C145A mice, 45% and 48% prevalence with median tumor sizes of 11 and 8 mm, and WT mice, 40% prevalence and median tumor size of 10 mm. These results provide evidence that residue C145 in hMGMT is required to reduce the prevalence of HCC in C3HeB/FeJ mice transgenic for hMGMT. © 2011 Wiley Periodicals, Inc.     

Blood wastage reduction using Lean Sigma methodology

BACKGROUND: Red blood cell (RBC) product wastage in hospitals is reported to range from 0.1% to 6.7%. Wastage at our institution averaged 4.4% of 63,000 issued RBC products. Data indicated that approximately 87% of wasted RBC units were either individual units that were out of blood bank for more than 30 minutes (dispensed but not administered) or units packed in transport containers that had temperature indicators affixed to each unit. We hypothesized that Lean Sigma methodology could be used to reduce RBC wastage by 50%. STUDY DESIGN AND METHODS: An interdisciplinary hospital team (transfusion medicine, nursing, and anesthesiology) used Lean Sigma methodology as a tool to reduce RBC product wastage, with a focus on container wastage, which was determined to yield the largest impact. Using the five‐part Lean Sigma process—define, measure, analyze, improve, and control—the team collected baseline wastage data, identified major factors affecting RBC product wastage, and implemented interventions to reduce amount of wastage. RESULTS: Factors identified as contributors to RBC wastage most amenable to improvement were lack of awareness and training of staff ordering and handling RBC products, management of temperature‐validated containers, inconsistent interpretation of RBC temperature indicators, and need for accountability when ordering blood products. Overall RBC product wastage decreased from 4.4% to a sustained rate of less than 2%. This reduction decreased the number of RBC units wasted by approximately 4300 per year, savings approximately $800,000 over the 4‐year period of the study. CONCLUSIONS: Lean Sigma methodology was an effective tool for reducing RBC wastage in a large academic hospital.