Faculty Bibliography

OBJECTIVE: The development of oral language in children with a cochlear implant is dependent on numerous factors. Although baseline achievements have been established, ceiling attainment levels have yet to be explored. One indicator of a higher capability level is the ability of children with implants to learn to communicate orally using a second language. The purpose of this research was to explore 1) the feasibility of children with cochlear implants developing oral fluency in a second language and 2) the factors that affect the development. STUDY DESIGN: Retrospective study of children fulfilling the criteria. SETTING: University medical center. PATIENTS: Eighteen profoundly hearing-impaired children who were reported to be bilingual. INTERVENTION: Cochlear implantation at age 5 or younger. MAIN OUTCOME MEASURES: The subjects were evaluated using standard speech perception and receptive and expressive language measures. RESULTS: The data revealed the ability of some pediatric cochlear implant recipients to develop competency in a second spoken language in addition to their primary language. Equally as important is the fact that the majority showed age-appropriate receptive and/or expressive language abilities in their primary language commensurate with normal-hearing children. CONCLUSION: High levels of achievement including the learning of a second spoken language are possible after implantation in the pediatric population. Variables include speech perception postimplantation, the linguistic environment, type of intervention, and educational placement

While intensive chemotherapy is recommended for the treatment of non-HIV related adult small non-cleaved lymphoma (SNCL), including Burkitt's and Burkitt-like lymphoma, optimal treatment for patients with HIV-associated SNCL is not known. We assessed remissions and survival in a cohort of 44 consecutive HIV positive patients diagnosed with SNCL at our hospital between June 2000 and November 2001 using chart and pathology data. Median follow-up, survival and survival at the median follow-up time were 4.5 months, 4 months and 49% respectively. Of this cohort 39% were complete responders (CR) and 36% were long-term lymphoma-free survivors. Two patients relapsed from CR. Short course intensive chemotherapy (McMaster) was administered to 23 patients; 17 received less intensive conventional combination chemotherapy; and four received single-agent chemotherapy or no treatment. In the McMaster group, 38% (9/23) achieved CR with no relapses. Seven patients (30%) died of toxicity compared with one (6%) in the less intensively treated group. Of the stage I patients, 75% (6/8) achieved long-term CR with half being treated conventionally. Conventional chemotherapy may be curative for early stage HIV-SNCL. In advanced disease, McMaster chemotherapy was found to be associated with substantial early mortality but was curative in a significant number of patients

Inhibitory transmission is critically involved in the functional maturation of neural circuits within the brain. However, the mechanisms involved in its plasticity and development remain poorly understood. At an inhibitory synapse of the developing auditory brain stem, we used whole cell recordings to determine the site of induction and expression of long-term depression (LTD), a robust activity-dependent phenomenon that decreases inhibitory synaptic gain and is postulated to underlie synapse elimination. Recordings were obtained from lateral superior olivary (LSO) neurons, and hyperpolarizing inhibitory potentials were evoked by stimulation of the medial nucleus of the trapezoid body (MNTB). Both postsynaptic glycine and GABAA receptors could independently display LTD when isolated pharmacologically. Focal application of GABA, but not glycine, on the postsynaptic LSO neuron was sufficient to induce depression of the amino acid-evoked response, or MNTB-evoked inhibitory postsynaptic potentials. This GABA-mediated depression, in the absence of MNTB stimulation, was blocked by a GABAB receptor antagonist. To assess whether a change in neurotransmitter release is associated with the LTD, the polyvalent cation, ruthenium red, was used to increase the frequency of miniature inhibitory synaptic events. Consistent with a postsynaptic locus of expression, we found that the mean amplitude of miniature events decreased after LTD with no change in their frequency of occurrence. Furthermore, there was no change in the paired-pulse ratio or release kinetics of evoked inhibitory responses. Together, these results provide direct evidence that activity-dependent LTD of inhibition has a postsynaptic locus of induction and alteration, and that GABA but not glycine plays a pivotal role

alphabeta1 integrins have been implicated in the survival, spreading, and migration of cells and tissues. To explore the underlying biology, we identified conditions where primary beta1 null keratinocytes adhere, proliferate, and display robust alphavbeta6 integrin-induced, peripheral focal contacts associated with elaborate stress fibers. Mechanistically, this appears to be due to reduced FAK and Src and elevated RhoA and Rock activities. Visualization on a genetic background of GFPactin shows that beta1 null keratinocytes spread, but do so aberrantly, and when induced to migrate from skin explants in vitro, the cells are not able to rapidly reorient their actin cytoskeleton toward the polarized movement. As judged by RFPzyxin/GFPactin videomicroscopy, the alphavbeta6-actin network does not undergo efficient turnover. Without the ability to remodel their integrin-actin network efficiently, alphabeta1-deficient keratinocytes cannot respond dynamically to their environment and polarize movements.

BACKGROUND AND PURPOSE: The measurement of relative cerebral blood volume (rCBV) and the volume transfer constant (K(trans)) by means of dynamic contrast-enhanced (DCE) perfusion MR imaging (pMRI) can be useful in characterizing brain tumors. The purpose of our study was to evaluate the utility of these measurements in differentiating typical meningiomas and atypical meningiomas. METHODS: Fifteen patients with pathologically confirmed typical meningiomas and seven with atypical meningiomas underwent conventional imaging and DCE pMRI before resection. rCBV measurements were calculated by using standard intravascular indicator dilution algorithms. K(trans) was calculated from the same DCE pMRI data by using a new pharmacokinetic modeling (PM) algorithm. Results were compared with pathologic findings. RESULTS: Mean rCBV was 8.02 +/- 4.74 in the 15 typical meningiomas and 10.50 +/- 2.1 in the seven atypical meningiomas. K(trans) was 0.0016 seconds(-1) +/- 0.0012 in the typical group and 0.0066 seconds(-1) +/- 0.0026 in the atypical group. The difference in K(trans) was statistically significant (P <.01, Student t test). Other parameters generated with the PM algorithm (plasma volume, volume of the extravascular extracellular space, and flux rate constant) were not significantly different between the two tumor types. CONCLUSION: DCE pMRI may have a role in the prospective characterization of meningiomas. Specifically, the measurement of K(trans) is of use in distinguishing atypical meningiomas from typical meningiomas

OBJECTIVE: To determine the effectiveness of the malleus to oval window wire-piston revision stapes surgery technique. STUDY DESIGN: A retrospective analysis of 243 stapes procedures performed by the senior author over a 10-year period identified 15 revisions. Five patients underwent a malleus to oval window wire-piston technique. All patients were followed for at least 6 months. The surgical outcome including audiologic data and complications are noted. METHODS: Stapes surgery was performed on an ambulatory basis by way of a transcanal approach under local anesthesia with monitored sedation by the same surgeon using a laser technique and a stapes wire-piston prosthesis. RESULTS: Among revision stapes procedures, there was no significant difference in the air-bone gap closure or complication rate between the incus to oval window and the malleus to oval window techniques. The average preoperative air-bone gap in all revisions was 32 dB, whereas the mean postoperative gap was 10 dB hearing loss. CONCLUSIONS: In experienced hands, revision stapes surgery using the malleus to oval window stapes wire-piston prosthesis is safe and effective

Loss of sensory function leads to atrophy or death within the developing CNS, yet little is known about the physiology of remaining synapses. After bilateral deafening, gramicidin-perforated-patch recordings were obtained from gerbil inferior colliculus neurons in a brain slice preparation. Afferent-evoked IPSPs had a diminished ability to block current-evoked action potentials in deafened neurons. This change could be attributed, in part, to a loss of potassium-dependent chloride transport function, with little change in K-Cl cotransporter expression. Treatments that suppressed chloride cotransport (bumetanide, cesium, and genistein) had little or no effect on neurons from deafened animals. These same treatments depolarized the E(IPSC) of control neurons. Semiquantitative RT-PCR and immunohistochemical staining indicated no change in the expression of chloride cotransporter mRNA or protein after deafness. Therefore, profound hearing loss leads rapidly to the disruption of chloride homeostasis, which is likely attributable to the dysfunction of the potassium-dependent chloride cotransport mechanism, rather than a downregulation of its expression. This results in inhibitory synapses that are less able to block excitatory events

In this issue of Neuron, Sjostrom et al. provide evidence for a novel presynaptic mechanism for coincidence detection in induction of timing-dependent LTD. In their scheme, simultaneous activation of presynaptic NMDA receptors and CB1 endocannabinoid receptors induces a long-lasting reduction in presynaptic transmitter release

p63 proteins are p53 homologs that are postulated to regulate squamous stem cell commitment. An immunohistochemical survey of p63 expression in normal thyroid and in reactive, neoplastic, and inflammatory thyroid disorders was performed. Sections from routinely fixed and processed archival thyroidectomy specimens were pretreated with citric acid, pH 6.0, for antigen retrieval, then incubated overnight with anti-p63 monoclonal antibody 4A4. Slides were stained using a streptavidin-biotin kit and diaminobenzidine as a chromagen, and then were counterstained with hematoxylin. The results showed that p63 expression was negative in normal thyroid tissue, nodular goiters, and oncocytic follicular adenomas. Positivity was rare and weak in follicular adenomas. p63-positive foci were commonly found in Hashimoto's thyroiditis (1 or more foci in 78.8% of cases), but rare in Graves' disease. Twenty-seven of 33 papillary thyroid carcinomas (81.8%) displayed p63-positive foci. Staining was uncommon in follicular carcinomas and rare in medullary carcinomas. One case of insular carcinoma was p63-positive. All squamoid structures were p63-positive; p63-positive structures morphologically consistent with solid cell nests were also identified. Based on the results of this study, we conclude that p63 is commonly expressed in papillary thyroid carcinoma and in Hashimoto's thyroiditis. Given the debated association of papillary thyroid carcinoma with Hashimoto's thyroiditis, it is possible that p63 expression may be a potential pathobiologic link between the two disorders. The finding of p63 in benign squamoid nests supports a possible interrelationship between these structures and both Hashimoto's thyroiditis and papillary carcinoma. The high percentage of papillary carcinomas with p63-positive foci appears to distinguish papillary carcinoma from other neoplasms originating in the thyroid