Cytosolic Ku70 regulates Bax-mediated cell death.

The first known function of Ku70 is as a DNA repair factor in the nucleus. Using neuronal neuroblastoma cells as a model, we have established that cytosolic Ku70 binds to the pro-apoptotic protein Bax in the cytosol and blocks Bax's cell death activity. Ku70-Bax binding is regulated by Ku70 acetylation in that when Ku70 is acetylated Bax dissociates from Ku70, triggering cell death. We propose that Ku70 may act as a survival factor in these cells such that Ku70 depletion triggers Bax-dependent cell death. Here, we addressed two fundamental questions about this model: (1) Does all Bax, which is a cytosolic protein, bind to all cytosolic Ku70? and (2) Is Ku70 a survival factor in cells types other than neuronal neuroblastoma cells? We show here that, in neuronal neuroblastoma cells, only a small fraction of Ku70 binds to a small fraction of Bax; most Bax is monomeric. Interestingly, there is no free or monomeric Ku70 in the cytosol; most cytosolic Ku70 is in complex with other factors forming several high molecular weight complexes. A fraction of cytosolic Ku70 also binds to cytosolic Ku80, Ku70's binding partner in the nucleus. Ku70 may not be a survival factor in some cell types (Ku70-depletion less sensitive) because Ku70 depletion does not affect survival of these cells. These results indicate that, in addition to Ku70 acetylation, other factors may be involved in regulating Ku70-Bax binding in the Ku70-depletion less sensitive cells because Ku70 acetylation in these cells is not sufficient to dissociate Bax from Ku70 or to activate Bax.

CLU blocks HDACI-mediated killing of neuroblastoma.

Clusterin is a ubiquitously expressed glycoprotein with multiple binding partners including IL-6, Ku70, and Bax. Clusterin blocks apoptosis by binding to activated Bax and sequestering it in the cytoplasm, thereby preventing Bax from entering mitochondria, releasing cytochrome c, and triggering apoptosis. Because increased clusterin expression correlates with aggressive behavior in tumors, clusterin inhibition might be beneficial in cancer treatment. Our recent findings indicated that, in neuroblastoma cells, cytoplasmic Bax also binds to Ku70; when Ku70 is acetylated, Bax is released and can initiate cell death. Therefore, increasing Ku70 acetylation, such as by using histone deacetylase inhibitors, may be therapeutically useful in promoting cell death in neuroblastoma tumors. Since clusterin, Bax, and Ku70 form a complex, it seemed likely that clusterin would mediate its anti-apoptotic effects by inhibiting Ku70 acetylation and blocking Bax release. Our results, however, demonstrate that while clusterin level does indeed determine the sensitivity of neuroblastoma cells to histone deacetylase inhibitor-induced cell death, it does so without affecting histone deacetylase-inhibitor-induced Ku70 acetylation. Our results suggest that in neuroblastoma, clusterin exerts its anti-apoptotic effects downstream of Ku70 acetylation, likely by directly blocking Bax activation.

Current use and barriers and facilitators for implementation of standardised measures in physical therapy in the Netherlands.

BACKGROUND: In many countries, the need for physical therapists to use standardised measures has been recognised and is recommended in clinical practice guidelines. Research has shown a lack of clinimetric knowledge and clinical application of measurement instruments in daily practice may hamper implementation of these guidelines. OBJECTIVES: The aims of our study were a) to investigate the current use of measurement instruments by Dutch physical therapists; b) to investigate the facilitators and barriers in using measurement instruments. METHODS: To get a complete and valid overview of relevant barriers and facilitators, different methods of data collection were used. We conducted a literature search, semi-structured interviews with 20 physical therapists and an online survey. RESULTS: Facilitators are the fact that most therapists indicated a positive attitude and were convinced of the advantages of the use of measurement instruments. The most important barriers to the use of measurement instruments included physical therapists' competence and problems in changing behaviour, practice organisation (no room; no time) and the unavailability and feasibility of measurement instruments. Furthermore, physical therapists indicated the need to have a core set of measurement instruments with a short user's instruction on application, scoring and interpretation. CONCLUSIONS: The main barriers are on the level of the physical therapist (lack of knowledge; not focusing on the use of outcome measures) and organisation (lack of time; availability; lack of management support).There seems to be a disparity between what physical therapists say and what they do. The majority of participating physical therapists indicated a positive attitude and were convinced of the advantages of the use of measurement instruments. However, the main problem for physical therapists is when to use which instrument for what patient (lack of knowledge). Furthermore, physical therapists indicated a need to compile a core set of measurement instruments with instructions concerning application, scoring and interpretation. Based on the identified factors, a number of strategies will be developed and evaluated in future studies.

Effects of a high-intensity task-oriented training on gait performance early after stroke: a pilot study.

OBJECTIVE: To investigate the feasibility and the effects on gait of a high intensity task-oriented training, incorporating a high cardiovascular workload and large number of repetitions, in patients with subacute stroke, when compared to a low intensity physiotherapy-programme. DESIGN AND SUBJECTS: Randomized controlled clinical trial: Forty-four patients with stroke were recruited at 2 to 8 weeks after stroke onset. MEASURES: Maximal gait speed assessed with the 10-metre timed walking test (10MTWT), walking capacity assessed with the six-minute walk test (6MWT). Control of standing balance assessed with the Berg Balance Scale and the Functional Reach test. Group differences were analysed using a Mann-Whitney U-test. RESULTS: Between-group analysis showed a statistically significant difference in favour of the high intensity task-oriented training in performance on the 10MTWT (Z = -2.13, P = 0.03) and the 6MWT (Z = -2.26, P = 0.02). No between-group difference were found for the Berg Balance Scale (Z = -0.07, P = 0.45) and the Functional Reach test (Z = -0.21, P = 0.84). CONCLUSION: A high-intensity task-oriented training programme designed to improve hemiplegic gait and physical fitness was feasible in the present study and the effectiveness exceeds a low intensity physiotherapy-programme in terms of gait speed and walking capacity in patients with subacute stroke. In a future study, it seems appropriate to additionally use measures to evaluate physical fitness and energy expenditure while walking.

Acetylation and deacetylation regulate CCAAT/enhancer binding protein beta at K39 in mediating gene transcription.

The transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) contains multiple acetylation sites, including lysine (K) 39. Mutation of C/EBPbeta at K39, an acetylation site in the transcriptional activation domain, impairs transcription of C/EBPbeta target genes in a dominant-negative fashion. Further, K39 of C/EBPbeta can be deacetylated by HDAC1, and HDAC1 may decrease C/EBPbeta-mediated transcription, suggesting that acetylation of C/EBPbeta at K39 is dynamically regulated in mediating gene transcription. Acetylation of endogenous C/EBPbeta at K39 is detected in adipose tissue, and also occurs in 3T3-L1 cells undergoing adipocyte conversion. In addition, mutation of K39 in C/EBPbeta impairs activation of its target genes encoding C/EBPalpha and PPARgamma, essential mediators of adipogenesis, as well as adipocyte genes for leptin and Glut4. These findings suggest that acetylation of C/EBPbeta at K39 is an important and dynamic regulatory event that contributes to its ability to transactivate target genes, including those associated with adipogenesis and adipocyte function.

Outcome measures in physiotherapy management of patients with stroke: a survey into self-reported use, and barriers to and facilitators for use.

UNLABELLED: OBJECTIVE. To investigate physiotherapists' self-reported use of outcome measures as recommended in the Dutch Clinical Practice Guideline on Physiotherapy Management of Patients with Stroke (CPGPS) and to assess perceived barriers to and facilitators for the use of outcome measures in everyday practice. METHOD: A 41-item survey, including the barriers and facilitators questionnaire (BFQ), was sent by post to 400 physiotherapists in each of the following settings in the Netherlands: acute care hospitals (ACH; n = 100), rehabilitation centres (RC; n = 100), nursing homes (NH; n = 100) and private physiotherapy practices (PPP; n = 100). RESULTS: One hundred and eighty-nine physiotherapists returned the survey (47%; ACH, n = 57; RC, n = 67; NH, n = 26 and PPP, n = 39) and the surveys of 167 physiotherapists involved in stroke settings were analysed. These physiotherapists reported regularly using three (median; range 0-7) of the seven recommended outcome measures, with those working in RC or ACH reporting a significantly higher use than their colleagues in PPP (4 vs. 0 and 3 vs. 0; p < 0.001 and p = 0.02, respectively). The BFQ revealed that there were setting-specific facilitators, such as 'a positive attitude towards outcome measures' (as mentioned by 93% of the physiotherapists) and 'acquaintance with outcome measures' (90%), and barriers such as 'changing routines' (32%), 'time investment' (29%) and 'financial compensation' (21%). CONCLUSION: Despite an almost uniformly positive attitude, physiotherapists infrequently use the outcome measures recommended in the CPGPS. Robust setting-specific tailored implementation strategies based on the reported barriers and facilitators are needed.

Akt regulates basic helix-loop-helix transcription factor-coactivator complex formation and activity during neuronal differentiation.

Neural basic helix-loop-helix (bHLH) transcription factors regulate neurogenesis in vertebrates. Signaling by peptide growth factors also plays critical roles in regulating neuronal differentiation and survival. Many peptide growth factors activate phosphatidylinositol 3-kinase (PI3K) and subsequently the Akt kinases, raising the possibility that Akt may impact bHLH protein function during neurogenesis. Here we demonstrate that reducing expression of endogenous Akt1 and Akt2 by RNA interference (RNAi) reduces neuron generation in P19 cells transfected with a neural bHLH expression vector. The reduction in neuron generation from decreased Akt expression is not solely due to decreased cell survival, since addition of the caspase inhibitor z-VAD-FMK rescues cell death associated with loss of Akt function but does not restore neuron formation. This result indicates that Akt1 and Akt2 have additional functions during neuronal differentiation that are separable from neuronal survival. We show that activated Akt1 enhances complex formation between bHLH proteins and the transcriptional coactivator p300. Activated Akt1 also significantly augments the transcriptional activity of the bHLH protein neurogenin 3 in complex with the coactivators p300 or CBP. In addition, inhibition of endogenous Akt activity by the PI3K/Akt inhibitor LY294002 abolishes transcriptional cooperativity between the bHLH proteins and p300. We propose that Akt regulates the assembly and activity of bHLH-coactivator complexes to promote neuronal differentiation.

Effects of visual feedback therapy on postural control in bilateral standing after stroke: a systematic review.

OBJECTIVE: To establish whether bilateral standing with visual feedback therapy after stroke improves postural control compared with conventional therapy and to evaluate the generalization of the effects of visual feedback therapy on gait and gait-related activities. DESIGN: A systematic review. METHODS: A computer-aided literature search was performed. Randomized controlled trials and controlled clinical trials, comparing visual feedback therapy with conventional balance treatments were included up to April 2005. The methodological quality of each study was assessed with the the Physiotherapy Evidence Database scale. Depending on existing heterogeneity, studies with a common variable of outcome were pooled by calculating the summary effect-sizes using fixed or random effects models. RESULTS: Eight out of 78 studies, presenting 214 subjects, were included for qualitative and quantitative analysis. The methodological quality ranged from 3 to 6 points. The meta-analysis demonstrated non-significant summary effect-sizes in favour of visual feedback therapy for weight distribution and postural sway, as well as balance and gait performance, and gait speed. CONCLUSION: The additional value of visual feedback therapy in bilateral standing compared with conventional therapy shows no statistically significant effects on symmetry of weight distribution between paretic and non-paretic leg, postural sway in bilateral standing, gait and gait-related activities. Visual feedback therapy should not be favoured over conventional therapy. The question remains as to exactly how asymmetry in weight distribution while standing is related to balance control in patients with stroke.

Paratonia: a Delphi procedure for consensus definition.

BACKGROUND AND PURPOSE: Paratonia is a motor problem that develops during the course of dementia. Definitions of paratonia used in the literature differ considerably, which has clinical implications and may lead to an undesirable heterogeneity in study populations. For this reason, we initiated a Delphi procedure with known experts in the field to establish an operational consensus definition of paratonia. METHODS: The Delphi procedure involved an anonymous and multistage approach presented as a questionnaire, with each stage building on the results of the previous one in order to reach consensus on the definition of paratonia. RESULTS: Eight of 17 experts agreed to participate in the study. After 4 rounds, the participants reached consensus on the following definition: paratonia is a form of hypertonia with an involuntary variable resistance during passive movement. The nature of paratonia may change with progression of dementia (eg, from active assistance (aka Mitgehen) to active resistance). The degree of resistance depends on the speed of movement (eg, slow > low resistance, fast > high resistance). The degree of paratonia is proportional to the amount of force applied and increases with progression of dementia. The resistance to passive movement is in any direction and there is no clasp-knife phenomenon. CONCLUSION: The Delphi procedure resulted in a comprehensive, operational definition of paratonia. Future research should focus on the reliability and validity of this definition.

Effectiveness of exercise therapy: a best-evidence summary of systematic reviews.

The purpose of this project was to summarise the available evidence on the effectiveness of exercise therapy for patients with disorders of the musculoskeletal, nervous, respiratory, and cardiovascular systems. Systematic reviews were identified by means of a comprehensive search strategy in 11 bibliographic databases (08/2002), in combination with reference tracking. Reviews that included (i) at least one randomised controlled trial investigating the effectiveness of exercise therapy, (ii) clinically relevant outcome measures, and (iii) full text written in English, German or Dutch, were selected by two reviewers. Thirteen independent and blinded reviewers participated in the selection, quality assessment and data-extraction of the systematic reviews. Conclusions about the effectiveness of exercise therapy were based on the results presented in reasonable or good quality systematic reviews (quality score > or = 60 out of 100 points). A total of 104 systematic reviews were selected, 45 of which were of reasonable or good quality. Exercise therapy is effective for patients with knee osteoarthritis, sub-acute (6 to 12 weeks) and chronic (> or = 12 weeks) low back pain, cystic fibrosis, chronic obstructive pulmonary disease, and intermittent claudication. Furthermore, there are indications that exercise therapy is effective for patients with ankylosing spondylitis, hip osteoarthritis, Parkinson's disease, and for patients who have suffered a stroke. There is insufficient evidence to support or refute the effectiveness of exercise therapy for patients with neck pain, shoulder pain, repetitive strain injury, rheumatoid arthritis, asthma, and bronchiectasis. Exercise therapy is not effective for patients with acute low back pain. It is concluded that exercise therapy is effective for a wide range of chronic disorders.

Using Outcome Measures in Daily Practice: Development and Evaluation of an Implementation Strategy for Physiotherapists in the Netherlands.

PURPOSE: To describe the development of an educational programme for physiotherapists in the Netherlands, two toolkits of measurement instruments, and the evaluation of an implementation strategy. METHOD: The study used a controlled pre- and post-measurement design. A tailored educational programme for the use of outcome measures was developed that consisted of four training sessions and two toolkits of measurement instruments. Of 366 invited physiotherapists, 265 followed the educational programme (response rate 72.4%), and 235 randomly chosen control physiotherapists did not (28% response rate). The outcomes measured were participants' general attitude toward measurement instruments, their ability to choose measurement instruments, their use of measurement instruments, the applicability of the educational programme, and the changes in physiotherapy practice achieved as a result of the programme. RESULTS: Consistent (not occasional) use of measurement instruments increased from 26% to 41% in the intervention group; in the control group, use remained almost the same (45% vs 48%). Difficulty in choosing an appropriate measurement instrument decreased from 3.5 to 2.7 on a 5-point Likert-type scale. Finally, 91% of respondents found the educational programme useful, and 82% reported that it changed their physiotherapy practice. CONCLUSIONS: The educational programme and toolkits were useful and had a positive effect on physiotherapists' ability to choose among many possible outcome measures.

Objectif : Décrire l'élaboration d'un programme de formation pour des physiothérapeutes aux Pays-Bas, deux trousses d'instruments de mesure et l'évaluation d'une stratégie de mise en œuvre. Méthode : L'étude a utilisé un concept de mesure contrôlé de type avant-après. Un programme de formation personnalisé pour l'utilisation des mesures de résultats a été élaboré; il consistait en quatre séances de formation et deux trousses d'instruments de mesure. Des 366 physiothérapeutes invités, 265 ont suivi le programme de formation (taux de réponse de 72,4 %), en plus de 235 physiothérapeutes témoins sélectionnés de façon aléatoire qui ne l'ont pas fait (taux de réponse de 28 %). Les résultats mesurés étaient l'attitude générale des participants envers les instruments de mesure, leur capacité de choisir des instruments de mesure, leur utilisation des instruments, l'applicabilité du programme de formation et les changements entraînés dans la pratique de la physiothérapie grâce au programme. Résultats : L'utilisation constante (non occasionnelle) des instruments de mesure a augmenté de 26 % à 41 % dans le groupe d'intervention; dans le groupe témoin, l'utilisation est restée presque la même (45 % par rapport à 48 %). La difficulté de choisir un instrument de mesure approprié a diminué de 3,5 à 2,7 sur échelle Likert à 5 points. Finalement, 91 % des répondants ont trouvé le programme de formation utile et 82 % ont indiqué que ce programme a changé leur pratique de la physiothérapie. Conclusions : Le programme de formation et les trousses se sont avérés utiles et ont eu un effet positif sur la capacité des physiothérapeutes à faire un choix parmi les nombreuses possibilités de mesure de résultats.

Trigeminal-palatal synkinesis.

A patient developed synkinetic movements of facial musculature and "crocodile tears" following the removal of a large acoustic neurinoma. A reflex palatal movement resulted from tactile stimulation of the lower part of the face as well. Analysis of the palatal movement suggested action of the tensor veli palatini muscle, acting in isolation. We believe the palatal contraction represents a synkinetic phenomenon involving both sensory and motor nerve fibers within the motor root of the trigeminal nerve.

Interinterpreter variability in determining the SP/AP ratio in clinical electrocochleography.

Calculating the SP/AP ratio in electrocochleography requires the interpreting audiologist to unequivocally identify the peak of the SP wave form. If different points are selected, different SP/AP ratios will result. To investigate this effect, 50 electrocochleographic tracings were sent to 10 different audiologists (500 tracings). Twenty of the wave forms sent to each audiologist were identified as "easy," 10 as "somewhat difficult," 10 as "very difficult," and 10 as "no response." The ranges and standard deviations of the resulting SP/AP ratios were quite high. Analysis of variance showed statistically significant differences in the very difficult and no response group. There is significant interinterpreter difference among SP/AP ratios calculated from the same tracing. This variability affects clinical patient management and investigational projects.

Microbiology of normal external auditory canal.

OBJECTIVES: To isolate and characterize bacteria and fungi from the healthy ear and to obtain susceptibility profiles on each bacterial isolate. STUDY DESIGN: Prospective. METHODS: Specimens were collected from the external canals and cerumen of healthy subjects. Species-level identification was obtained by combining phenotypic and genotypic data. End-point minimal inhibitory concentration testing was performed using National Committee for Clinical Laboratory Standards recommended methods. RESULTS: One hundred sixty-four subjects were cultured. Seventeen canal and 16 cerumen specimens showed no growth. One hundred forty-eight cerumen specimens yielded 314 organisms, including 23 fungi. One hundred forty-seven canal specimens yielded 310 organisms, including 7 fungi. Of 291 bacteria isolated from cerumen, 99% were Gram-positive. Of 302 bacteria isolated from the canal, 96% were Gram-positive. Staphylococci were 63% of both the cerumen bacteria and the canal bacteria. Coryneforms represented 22% of the bacteria in cerumen and 19% in the canal. Turicellaotitidis was the primary coryneform isolated from both the canal and the cerumen. Streptococci-like bacteria were 10% from the cerumen, 7% from the canal. In both cerumen and canal, Alloiococcusotitis was more than 95% of the streptococci-like bacteria. Fifteen gram-negative organisms were isolated from the canal and cerumen, including four Pseudomonas aeruginosa strains. The percentages of Staphylococcus epidermidis isolates that had high-level resistance (> or =8 microg/mL) were as follows: to neomycin, 28% from cerumen and 11% from the canal; to oxacillin, 28% from cerumen and 25% from the canal; and to ofloxacin, 15% from cerumen and 19% from the canal. CONCLUSIONS: Turcellaotitidis and A. otitidis were present with a much higher frequency than previously described, lending evidence that they be considered normal otic flora. Corynebacterium auris, previously reported only in children, was isolated from normal adults.

Preoperative functional assessment of auditory cortex in adult cochlear implant users.

OBJECTIVES: To explore functional neuroanatomical responses to auditory stimulation before and after implantation. STUDY DESIGN: A prospective study of three cochlear implant candidates (pure-tone averages of 90 dB HL or greater bilaterally and hearing in noise test [HINT] performances of <40%) in which regional cerebral blood flow (rCBF) was assessed using single photon emission computed tomography (SPECT). METHODS: Candidates watched a 15-minute videotaped story under four conditions: audio presented monaurally in the right and left ears (aided), audio presented binaurally (aided), and visual-only presentation of the story. Five minutes into each story, 20 to 25 mCi of technetium 99m (99mTc) hexamethyl-propyleneamine-oxime (HMPAO) (Ceratec; Nycomed Amersham, Princeton, NJ, U.SA) was injected over a 30-second period to ensure that subjects were unaware of tracer administration. Subjects were scanned for 20 minutes using a PRISM 3000 gamma camera (Picker International, Cleveland, OH, U.S.A.). Data were normalized and co-registered, and subtraction images were compiled. Subtraction images contrasted activation patterns generated under the visual-only control condition to the auditory activation states acquired monaurally and binaurally. RESULTS: Right and left ear monaural stimulation in normal hearing subjects resulted in significant bilateral activation of Brodmann areas 41, 42, 21, 22, and 38. Although substantial intersubject response variability was noted, subjects generally failed to bilaterally activate these areas under monaural hearing aid presentations; however, bilateral activation of areas 41 and 22 was noted under binaural presentations. CONCLUSIONS: Despite relatively similar hearing losses in each ear, significant differences in preoperative auditory cortex activation were observed between ears. These data suggest that functional brain imaging provides a useful tool for exploring the responsiveness of the auditory cortex in cochlear implant candidates.

Intrasubject test-retest variability in clinical electrocochleography.

Seventeen healthy volunteers without a history of auditory or vestibular difficulty and with normal screening audiometry had bilateral (34 ears) electrocochleography performed repeatedly at 1-week intervals. Each subject had from four to seven electrocochleograms performed on each ear. Measurements were made in the external auditory canal using a gold-foil "TIPtrode." Amplitude and latency for the summating potential (SP) and action potential (AP) were measured and SP/AP ratios were calculated. Averages and standard deviations for amplitude, latency, and SP/AP ratios were computed. The average SP/AP ratio was 0.22 with a standard deviation of 0.06. The range was 0.04 to 0.50. The average difference between the highest and lowest SP/AP ratio for a given individual was 0.155 (i.e., the range 0.03 to 0.31) with a standard deviation of 0.07. These normative data are useful in assessing the results of dehydration electrocochleography and in establishing how much test-retest variation is required to suggest pathology.

Catastrophic otologic injury from oral jet irrigation of the external auditory canal.

Jet irrigation is an accepted method for removal of cerumen from the external auditory canal. Even at a submaximal power setting, oral jet irrigators can generate enough force to rupture the tympanic membrane. Parameters for safe use of these irrigators have never been established. Three cases are reported in which, in addition to tympanic membrane rupture, oral jet irrigators caused ossicular disruption, round and oval window fistulae, and subluxation of the stapedial footplate. A prospective study performed on 25 fresh cadavers demonstrated a 6% incidence of tympanic membrane perforation when the power setting was one-third full power or greater. Recommendations are made for safe use of oral jet irrigators for removal of external auditory canal cerumen.

Verification of improved patient outcomes with a partially implantable hearing aid, The SOUNDTEC direct hearing system.

INTRODUCTION: Partially implantable hearing devices have been developed to address some of the user-perceived shortcomings of standard amplification systems. Partially implantable devices are purported to provide improved sound quality as a result of decreased occlusion, decreased feedback, and enhanced clarity resulting from increased high-frequency gain. Such improvements may result in greater user satisfaction. To justify selection of a partially implantable device and undergoing a minor surgical procedure, verification techniques must be used to document user improvement or increased satisfaction over conventional amplification. OBJECTIVE: To evaluate patient satisfaction with the SOUNDTEC direct hearing system. STUDY DESIGN: Within-subjects repeated measures design. METHODS: Objective and subjective evaluation pre- and post-implantation with the SOUNDTEC device. Verification techniques included tonal functional gain measures with traditional amplification and the SOUNDTEC device, word recognition in quiet (NU-6) and in noise (SPIN), the Abbreviated Profile of Hearing Aid Benefit (APHAB), and the Hough Ear Institute Profile (HEIP). RESULTS: Although there was no significant difference between optimal traditional amplification and the SOUNDTEC device for speech perception measures, the SOUNDTEC device yielded statistically significant increased high-frequency functional gain. Subjective reports indicated that the SOUNDTEC device provides a cleaner, more natural sound without feedback than traditional amplification. CONCLUSIONS: Partially implantable hearing aids may address some of the limitations of traditional amplification systems.

An animal model for external ear canal inflammation.

OBJECTIVE: To develop an animal model for testing efficacy of anti-inflammatory drugs designed to treat external ear canal (EAC) disease. METHODS: Histological and morphometric methods were used to characterize EAC inflammation produced by topical application of tetradecanoylphorbol acetate (TPA) in mice. The effects of both single and repeated TPA applications were studied. A treatment trial was performed to evaluate the effects of a ciprofloxacin/hydrocortisone suspension on TPA-induced EAC inflammation. In 10 animals, two bilateral applications of TPA were made, spaced 24 hours apart. Immediately after the second TPA application, otic suspension was applied unilaterally four times over a 48-hour period. The contralateral EACs were left untreated to provide TPA-only controls. RESULTS: Twenty-four hours after a single TPA application, EAC skin showed polymorphonuclear (PMN) leukocyte infiltration, vascular dilation, and thickening of the dermis and epidermis. Dermal and epidermal thickening were more pronounced after two TPA applications and PMN leukocyte infiltration remained high 48 hours after a second TPA placement. After treatment with the otic suspension, PMN leukocyte counts were reduced by an average of 76% relative to EACs that received TPA only. There was also statistically significant reduction of dermal swelling and a trend toward reduced epidermal thickness. Vascular dilation was clearly reduced as well EACs that received four applications of the suspension alone showed no adverse effects compared with those that received saline. CONCLUSION: TPA-induced inflammation of the mouse EAC provides a suitable model for testing the therapeutic efficacy of anti-inflammatory agents being considered for clinical use.

Stereotastic radiosurgery for glomus jugulare tumors.

OBJECTIVES/HYPOTHESIS: Surgery is considered to be the mainstay of treatment for glomus jugulare tumors. A subset of patients are poor surgical candidates based on age, medical problems, tumor size, or prior treatment failure. The purpose of this study was to review our results with stereotactic radiosurgery (gamma knife treatment) in this group of patients, with particular attention to adverse reactions and symptom relief. STUDY DESIGN: Retrospective review and phone survey. METHODS: Charts were reviewed for size and location of tumor, history of previous treatment, symptoms before and after treatment, amount of radiation received, acute and late complications, and functional level before and after treatment. Pre-treatment and posttreatment magnetic resonance imaging scans were also reviewed. Identified patients were then contacted for a phone interview. RESULTS: Eight patients were identified. Phone interviews were conducted with four patients. Four patients had failed previous treatment. Follow-up ranged from 7 to 104 months. One patient experienced an acute complication: intractable vertigo requiring hospitalization. No patient experienced delayed cranial neuropathies. No patient reported worsening of any of the following symptoms: pulsatile tinnitus, hearing loss, facial weakness, hoarseness, or difficulty swallowing. Three patients reported improvement in their pulsatile tinnitus. Two patients reported improvement in hearing loss, and one patient each reported improvement in vertigo and difficulty swallowing. CONCLUSIONS: Preliminary results suggest that stereotactic radiosurgery is useful to control symptoms and may be delivered safely in patients with primary or recurrent glomus jugulare tumors who are poor surgical candidates.