Liver fibrogenesis due to cholestasis is associated with increased Smad7 expression and Smad3 signaling.

BACKGROUND/AIMS: Profibrogenic TGF-beta signaling in hepatic stellate cells is modulated during transdifferentiation. Strategies to abrogate TGF-beta effects provide promising antifibrotic results, however, in vivo data regarding Smad activation during fibrogenesis are scarce. METHODS: Here, liver fibrosis was assessed subsequent to bile duct ligation by determining liver enzymes in serum and collagen deposition in liver tissue. Activated hepatic stellate cells were identified by immunohistochemistry and immunoblots for alpha smooth muscle actin. Cellular localization of Smad3 and Smad7 proteins was demonstrated by immunohistochemistry. RTPCR for Smad4 and Smad7 was conducted with total RNA and Northern blot analysis for Smad7 with mRNA. Whole liver lysates were prepared to detect Smad2/3/4 and phospho- Smad2/3 by Western blotting. RESULTS: Cholestasis induces TGF-beta signaling via Smad3 in vivo, whereas Smad2 phosphorylation was only marginally increased. Smad4 expression levels were unchanged. Smad7 expression was continuously increasing with duration of cholestasis. Hepatocytes of fibrotic lesions exhibited nuclear staining Smad3. In contrast to this, Smad7 expression was localized to activated hepatic stellate cells. CONCLUSIONS: Hepatocytes of damaged liver tissue display increased TGF-beta signaling via Smad3. Further, negative feedback regulation of TGF-beta signaling by increased Smad7 expression in activated hepatic stellate cells occurs, however does not interfere with fibrogenesis.

Clinical application of magnetic resonance imaging in 30 cochlear implant patients.

OBJECTIVE: The goal of this investigation was to provide evidence that magnetic resonance imaging (MRI) can be performed safely and effectively on cochlear implant patients who require diagnosis of additional diseases. STUDY DESIGN: A retrospective study was performed over 5 years. In a total of 300 patients with cochlear implants at the authors' center, MRI was performed whenever it was medically indicated. SETTING: All patients underwent scanning in a Philips Gyroscan T10-NT MRI machine, using commercially available Powertrac 3000 software. PATIENTS: All patients with cochlear implants for whom MRI was indicated (n = 30) were included in this study. They had a wide variety of conditions necessitating MRI, including cervical discus prolapse, hypophyseal adenoma, epipharynx carcinoma, knee degeneration, parotid tumor, and preoperative evaluation for reimplantation and bilateral implantation. RESULTS: No adverse effects from the MRI were reported by any of the patients. The cochlear implants all retained their function. All images were of diagnostic value. Because of the MRI, the patients did not need to undergo additional, more invasive and expensive diagnostic procedures. Examples of MRI images from 5 patients are shown. CONCLUSIONS: MRI on cochlear implant patients, using the Med El Combi 40 and Nucleus mini 22 series at 1 Tesla, can be a safe procedure. Removal of any magnet is not necessary.

Radical cavities and cochlear implantation.

Profoundly deaf patients with chronic suppurative otitis media have been contraindicated for cochlear implantation in the past. Complications such as infection of the radical cavity, fat necrosis, skin flap problems, change in electrode position and cholesteatoma have occurred in subjects with radical cavities. The aim is to create a dry, self-cleansing, infection-free cavity. This is essential in patients about to receive a cochlear implant, as infection may be introduced into the cochlea at the implantation site and destroy any remaining neural elements. The aim of this paper was to show that it is possible to obliterate the radical cavity and perform cochlear implantation using a one-step surgical technique. Eight patients suffering from long-term bilateral chronic middle ear diseases with chronic sepsis leading to severe hearing impairment underwent cochlear implant surgery. No major complications were observed in these subjects.

Perimodiolar electrodes in cochlear implant surgery.

Perimodiolar-positioned cochlear implant electrodes have been developed in order to bring the electrode contacts as close as possible to the spiral ganglion cells, which are the target of electrostimulation. This results in lower electrical thresholds, higher dynamic ranges and less channel interaction when compared with normal implant electrodes which are usually located peripherally within the scala tympani. In this study we evaluated 4 different types of perimodiolar electrode: the Clarion Preformed electrode, the Clarion Preformed electrode with positioner, the Nucleus Contour electrode and the Med-El Perimodiolar Combi 40 electrode. These devices require different approaches to achieve a perimodiolar electrode position. The electrodes were inserted in fresh human temporal bones. After processing these bones with the electrodes in situ by employing a sawing, grinding and polishing technique, the inner ear structures as well as the electrode positions could be evaluated in detail. All electrode types studied had a more or less perimodiolar position; however, each type produced a certain amount of trauma to cochlear structures which is discussed in relation to mechanical properties. Further human temporal bone studies with improved perimodiolar cochlear implant electrodes are necessary in order to find an optimized type of electrode.

Hearing performance in noise of cochlear implant patients versus severely-profoundly hearing-impaired patients with hearing aids.

It is possible for most post-lingually deaf patients to attain significant open speech recognition following cochlear implantation. In contrast, many severely-profoundly sensorineural hearing-impaired patients receive no benefit from their hearing aids, especially in situations with background noise. The aim of the study was to evaluate the speech recognition ability in quiet and in noise of post-lingually deaf adults implanted with Combi 40/40+ cochlear implants versus severely-profoundly sensorineural hearing-impaired patients fitted with hearing aids. For this purpose, we tested two groups of patients: one that had received cochlear implants (n=22) and a group of subjects with severe-profound sensorineural hearing impairment, fitted with hearing aids (n = 15). All of the patients were tested using the Hochmaier, Schultz, and Moser Discrimination Test in quiet and noise. The results of the study demonstrate that most of our cochlear implant patients received a substantial benefit from their implant, achieving scores of 70 to 100 per cent (mean, 90 per cent) for the numbers test and 10 to 72 per cent (mean, 43 per cent) for the monosyllable test 1 year after implantation. Even in situations with background noise, scores of 1 to 99 per cent (mean, 45.65 per cent) for a signal to noise ratio (SNR) of +15 dB 1 year following the implantation improved to 7 to 95 per cent (mean, 50.7 per cent) at 2 years and 8 to 99 per cent (mean, 60 per cent) at 3 years after implantation. These results are significantly (p<0.04) superior to the hearing aid patients' scores of 1 to 64.2 per cent (mean, 26.7 per cent) for a SNR of 15 dB. The results of the present study may have clinical implications in regard to selection of candidates for cochlear implantation.

Fixation of the electrode array with bone paté in cochlear implant surgery.

The aims of this study are to report on our experiences using a bone paté (a mixture of bone dust and fibrin glue) fixation technique of the Combi 40/Combi 40+ electrode array during cochlear implant surgery. A retrospective study involving 57 patients implanted with Combi 40/Combi 40+ cochlear implants over 31 months fixated with bone paté was performed, utilizing our electrical fitting data as well as re-operation and X-ray findings. We found no signs of electrode retraction in any of the 57 patients. Electrical fitting data showed no reduction in the number of active channels between the first and last times patients were evaluated (a period of 4-31 months). Furthermore, a comparison of X-rays performed within the first week following cochlear implant surgery and again 7-27 months later showed no signs of electrode retraction in 10 patients. Three patients who required re-operations after implantation allowed us the opportunity to examine the effectiveness of the bone paté fixation and revealed new bone growth with the electrode fixed in place. Histological examinations of the newly built bone showed laminar and compact bone structures. The use of bone paté was thus found to be a suitable method of electrode fixation in cochlear implant surgery. Compared with other fixation methods, it is inexpensive and uses no foreign materials.

Short-term effect of auditory feedback on fundamental frequency after cochlear implantation.

The present study evaluates the short-term effect of cochlear implantation on the fundamental frequency (FO) of 13 deaf patients. All patients were provided with the Combi 40+ cochlear implant. Voice recording was made pre- and 3 months post-implantation. The FO was analysed using X-Tools software. The results showed that 38 per cent of our subjects had a statistically significant decrease of their mean F0 (p=0.001) at 3 months following implantation. It was also observed that the patients tended to have a lower F0 postoperatively approaching the normal range of F0. A large variability in F0 was noticed among the deaf subjects but no correlation with the duration of deafness was seen. There was also no correlation between speech recognition and speech production.

[Rehabilitation of hearing-impaired patients with cochlear implants: a review]. / Rehabilitation Hörgeschädigter mit Cochlear-Implantaten--eine Ubersicht.

The aim of this paper is to provide an overview of the cochlear implant. The history of this entity is traced from the early development of implants, involving the stimulation of the hearing nerve, up to the currently available standard multichannel implants. The physiological background is also elucidated. A cochlear implant consists of an implantable portion which lies within the ear, and of parts that are worn externally on the body. Differences between the first implants and those now in use are as follows: transcutaneous information and energy transmission, the position of the electrode in the ear, and the configuration of the electrode. Differences between the currently available implants mainly concern the number of electrodes, speech coding strategies and the mode of electrode stimulation. Almost all of the most recent implants are equipped with electrodes that are implanted in the tympanic scale of the cochlea.

[Cochlear implantation--the Viennese surgical technique]. / Cochlear-Implantation--die Wiener Operationstechnik.

The aim of the study was to report the current surgical procedure that has been established on the basis of about 200 implantations with the Combi 40/40+ implant system. The outstanding features of this procedure are the skin incision and the fact that the electrode can be inserted up to a depth of 34 mm into the cochlea. In order to provide better magnetic positioning of the external parts, a flap-reducing technique may be required. For insertion we used a soft surgery method to preserve structures within the cochlea. In some cases we were able to inspect the cochlea with microendoscopes, which helped to prevent electrode kinking, since fibrous obliterations were found before the insertion. For electrode fixation in the mastoid cavity we used bone paté.

[Intracochlear position of cochlear implant electrodes]. / Intracochleäre Position von Cochlear-Implantat-Elektroden.

The insertion of cochlear implant electrodes in human temporal bones may be associated with the destruction of structures within the cochlea. The aim of this study was to measure such insertional trauma by means of histologic processing of implanted human temporal bones following implantation of a Combi 40/40+ electrode array (Med-El, Innsbruck). We implanted 6 human temporal bones with original electrodes (3 with Combi 40 and 3 with Combi 40+). In 4 bones Healon was used for electrode insertion. The histological investigation was performed after radiographic evaluation of the position of the electrode. For the histological procedure we used a technique which keeps the electrodes in position within the cochlea. In these slides we could clearly identify the electrodes in the tympanic scale. When inserted properly (point of first resistance) no trauma occurred in the basal portion of the cochlea and minimal trauma in the middle portion of the cochlea.

[Preoperative imaging of the inner ear prior to the implantation of a multichannel cochlear implant using computed and MR technology]. / Präoperative Bildgebung vor dem Einsetzen eines multikanalikulären Cochlear-Implantates mittels Computer- und Magnetresonanztomographie der Innenohrregion.

CT and MRT are now standard examinations prior to insertion of a cochlear implant. Both methods have advantages and disadvantages in terms of discovering potentially pathological structures in the inner ear. The aim of this study was to evaluate the pros and cons of using CT and MRT before cochlear implantation. CT is usually performed using axial planigraphic planes. Like MRT, bone-specific CT is helpful in the diagnosis of congenital and acquired changes within the inner ear. Congenital defects in the meatus acusticus internus, the endolymphatic duct and sac, the cochlea and the vestibulum can be diagnosed and also quantified. Infectious morphologic changes can be seen on CT images in their terminal residual state (sclerotic tissue). However, acute inflammation and fibrotic tissue is not visible on CT. T2-specific MRT images are very fluid sensitive and play a major role in preoperative cochlear implant diagnosis. This examination demonstrates fluid within the peri- and enolymphatic cave and permits the diagnostician to determine whether congenital or acquired diseases have destroyed such fluid-filled cavities. In order to demonstrate pathological changes in the temporal bone and neural structures in the inner ear, MRT is the preferred method. Displaying the modiolus and the cochlear nerve is extremely important because, in their absence, a cochlear implantation may be contra-indicated. MRT also demonstrates other neural structures such as the facial nerve. This information may be important for the surgeon, e.g. the state of the pneumatic system in the mastoid cavity (which is best visualised by bone-specific CT).

[Speech discrimination in post-lingually deaf patients with cochlear implants]. / Sprachdiskrimination bei postlingual ertaubten, Cochlear-implantierten Patienten.

The aim of this study was to measure the speech discrimination performance of postlingually deaf patients using the Combi 40/40+ cochlear implant (Med-El, Innsbruck). The speech perception performance of 37 adults was tested over a time span of three years. We used a standardised test battery comprising number, monosyllable, sentence, consonant and vowel discrimination tests. Testing was performed immediately after initial fitting and 1, 3, 5, 12, 24, and 36 months thereafter. The average correct answers for all tests were as follows: right after the implantation 29.1%, after 1 month 46.7%, after 3 months 53.9% after 1 year 63.5% and after 3 years 68.5%. Some patients reached a number discrimination rate of 100%. The discrimination for monosyllables averaged 41.1% two years after implantation. The results demonstrated continuous improvement of speech perception, even after three years following implantation.

[Hearing and speech discrimination scores of prelingually deaf children with cochlear implants]. / Hör- und Sprachdiskriminationsleistungen prälingual ertaubter Cochlear-implantierter Kinder.

The goal of this study is to report mean values of speech perception performance in prelingually deaf children who received a Combi 40/40+ cochlear implant. Thirty-one patients were included in the study. The time span ranged over 3 years, during which time the Evaluation of Auditory Responses to Speech (EARS) test battery was used in the children. The EARS battery contains 4 measures of closed-set speech perception and 3 open-set tests. The mean test results exhibited steady improvement in all parts of the EARS test battery, even up to 3 years post-implantation. The mean preoperative scores were 0.3%, increasing to 92.3% at 36 months post-implantation for the best children. Results for the closed-set testing measures were most encouraging, with some children reaching fairly high levels of speech perception and achieving scores as high as 98.7% at the 36-month evaluation. The congenitally and prelingually deaf children in our study showed continuous improvement in both closed and open set speech perception following cochlear implantation, although individual variations in performance were noted.

[Speech discrimination in noise for patients with cochlear implants]. / Sprachdiskrimination im Störschall bei Cochlear-implantierten Patienten.

The aim of the study was to evaluate the speech discrimination ability of postlingually deaf adults implanted with the Combi 40 cochlear implant in noise and to compare the results with the speech discrimination ability of patients provided with hearing aids. The 12-month postoperative hearing performance of 12 consecutive patients was tested using a sentence discrimination test in quiet and noise. The results of the present study demonstrate that all patients obtained substantial benefit from their implants even in situations coupled with noise. The speech understanding of cochlea-implanted patients appears to be better than that of patients provided with hearing aids. Very high scores (mean, 40.2%) were achieved at a signal-noise ratio of 15 dB.

[Preoperative diagnostic procedures before cochlear implantation]. / Präoperative Diagnostik vor einer Cochlear-Implantation.

About 200 patients are considered each year for cochlear implant recipiency. Only 1/4 of these candidates actually receive an implant. The aim of the study is to discuss the preoperative procedure we use, which is aimed to exclude patients who would not benefit from an implant. A cochlear implant is an example of very expensive high-profile medical therapy, a single implant costing about 280,000 Austrian schillings. The aim of the preoperative diagnostic procedure is to select the right patients, with a view to providing the best audiologic outcome. During the past 20 years, important parameters have been identified to determine suitable patients. Candidates for a cochlear implant are infants and children (independent of the etiology of deafness or high-grade hearing loss), as well as postlingual deaf adults. Congenitally deaf adults or teenagers are considered unsuitable to receive an implant.

[Postoperative imaging and evaluation of the electrode position and depth of insertion of multichannel cochlear implants by means of high-resolution computed tomography and conventional X-rays]. / Postoperative Darstellung und Erfassung der Lage und Insertionstiefe von multikanalikulären Cochlear-Implantaten durch die hochauflösende Computertomographie und durch das Nativröntgen.

Following cochlear implantation, postoperative imaging of the electrode is very important in order to measure the depth of insertion and the position of the electrode, so that kinking and incorrect electrode placement can be clearly identified. The aim of this study was to outline the diagnostic value of CT and conventional X-ray for these parameters. For this purpose we obtained radiographs of patients who had received a cochlear implant. Computed tomography was performed by obtaining axial sections. For conventional X-ray we used digital imaging, utilising a modified Chausse III projection. The images were then rated according to electrode position, insertion depth and possible complications. We also measured the radiation dose using a dummy and evaluated the cost of each examination. Both examinations permit excellent identification of electrode position and insertion depth. However, the depth of insertion can be measured much more accurately by means of digital X-ray. The radiation dose of CT was 230 times higher than that of conventional X-ray and the cost of CT 5 times that of digital X-ray.

[Clinical utilization of magnetic resonance imaging for patients with cochlear implants]. / Klinische Anwendung von Magnetresonanztomographie bei Cochlear-implantierten Patienten.

To date, MR imaging is absolutely contraindicated in cochlear-implanted patients. The aim of this study is to document the potential value of MR imaging in such patients, without injurious or side effects and without technical device failure. After in vitro experimental testing, 25 cochlear implanted patients underwent MRI. Radiological evaluation was also possible. The use of 1-Tesla fast spin echo sequences minimised artifacts. All cochlear implants are still in working order; no changes in fitting data or a reduction in speech understanding were observed. MR helped to avoid other invasive medical procedures.

[Cochlear implantation and auditory feedback]. / Cochlear-Implantation und auditive Rückkopplung.

The aim of the present study was to evaluate the short term effect of cochlear implantation on the fundamental frequency and the articulation of 13 patients. This investigation objectives for the first time the changes of fundamental frequency and articulation in cochlear implant patients. All postlingual deaf patients were provided with a Combi 40+ cochlear implant. Voice recording was performed pre- and three months post-implantation. The voice data was analyzed using the "X-Tool" software. The results show that 38% of the patients had a significant (p < 0.05) decrease of F0 mean three months after implantation. A postoperative decrease of F0 towards the normal range was observed generally in all patients. Spectographs pre- and post-implantation showed that the articulation improved already 3 months after partial restoration of auditory feedback. A large variability of F0 was noticed among the deaf subjects, but no correlation to the duration of deafness could be established.