Intracellular calcium and outer hair cell electromotility.

The influence of increased intracellular calcium level on outer hair cell (OHC) electromotility was examined by means of transcellular electrical stimulation in a partitioning microchamber. Electromotile activity was measured before and after application of the calcium ionophore ionomycin, which promotes the inflow of extracellular calcium, as well as its release from intracellular calcium stores. The ionomycin solvent, dimethyl sulphoxide (DMSO), by itself elicited a significant decrease in the magnitude of OHC electromotility. The DMSO effect was counteracted by 10 microM ionomycin and was reversed by 50 microM ionomycin. The increase in electromotility is partially mediated by a calmodulin-dependent mechanism, since W7, a calmodulin antagonist, attenuated the 50 microM ionomycin-induced motility increase. Our results suggest that the electromotility magnitude increase in isolated OHCs due to ionomycin is a calcium/calmodulin-dependent phenomenon.

Air caloric computer system application in monitoring vestibular function changes after cochlear implantation.

INTRODUCTION: The computer-based ENG system's analytical routine refinements are available only in research laboratories. The computer-based system contains a stimulator for saccadic eye-movement and an air caloric stimulator interconnected to the registration program and analysis software. Several authors have reported the preoperative and postoperative vestibular functions in cochlear implant patients. The safe examination of the operated ear and comparison of the preoperative and postoperative average slow phase velocities of the caloric nystagmus is possible using the air caloric computer system. METHODS: The authors have used a computer-based ENG system with caloric air stimulation, which is very useful for examination of the operated ear. The vestibular system of patients with total deafness was examined before and after the cochlear implantation. The results of 60 vestibular examinations of 64 patients are reported. RESULTS: The vestibular function in the operated ear was found unchanged in 20 patients. In 14 patients the vestibular function was worse. In 16 patients the postoperative vestibular responsiveness improved. The detailed data analysis of 10 patients in whom preoperative and postoperative vestibular examination was similar was performed by the authors. The preoperative and postoperative average slow phase velocity values and the relative canal paresis was observed. The values demonstrated that the caloric responsiveness of the operated ear improved in few cases. CONCLUSIONS: The computer-based air caloric system is a useful and safe method in evaluation of the vestibular system changes after ear surgery. The reason of the improvement of vestibular responsiveness is not clear. The results need further investigation to solve the problem of vestibular responsiveness improvement after cochlear implantation.

Apoptotic and mitotic activity in squamous cell carcinoma cells after combined modality treatment with gamma-irradiation and dibromodulcitol.

A-431 squamous cell carcinoma cells were treated in vitro with either 4 Gy radiation of 15 (or 45) microg/ml dibromodulcitol (DBD), as well as with combined 4 Gy irradiation and DBD, with the latter as either a pretreatment or post-treatment. DBD alone or in combination with radiation had a greater effect on cell proliferation than the effect of radiation alone. The difference is due to a higher level of apoptosis induced by DBD, especially in conjunction with radiation. Such a combination may therefore be useful in the treatment of squamous cell carcinoma, which in general responds poorly to radiation therapy.

New method for inserting and fixing the active electrode during cochlear implantation.

Cochlear implantation has been performed for 15 years by the authors; altogether 117 implantations were carried out during this period. Different techniques had been used: at first after having performed atticoantrotomy the active electrode was inserted through posterior tympanotomy but fixing the electrode with this method was relatively not that easy. During the last 6 years implantations were carried out using the authors' new method. At the beginning of the operation cochleostomy was prepared by means of lateral tympanotomy. Introduction of the electrode was performed through a tunnel that had been drilled previously through the posterior wall of the external auditory canal. With a piece of muscle the active electrode was properly secured in the cochleostomy and also a narrow tunnel was prepared in the posterior wall for securing the cable with a Dacron tie. The authors' method of implantation proved to be perfect for introducing the electrode and also for fixing it with long-lasting results.

Prognostic significance of P53 histochemistry and DNA histogram parameters in head and neck malignancies.

BACKGROUND: The aim of the study was to determine the role of quantitative pathological parameters in prognosis of head and neck malignancies. MATERIALS AND METHODS: 51 head and neck squamous cell carcinoma patients were examined for mutant p53 gene expression (45 out of 51 patients) by immunohistochemistry and for cellular DNA-content (44 out of 51 patients) using digital picture analyzer. Statistical analysis was performed using BMDP package. RESULTS: No correlation with prognosis was found for age, sex, localization, T-classification and therapy. There was significant relationship between N-status and overall survival (p = 0.0008). No correlation was found with overall and disease-free survival for either histologic type or grading. P53: No significant correlation was detected with overall survival. A relationship was found between mutant p53 and metastasis-free time (p = 0.06). Ploidy: There were no significant differences between aneuploid and euploid tumors for either disease-free or overall survival. Synthetic (S)-phase fraction: A correlation was found for both survival rates (p = 0.029) and metastasis-free time (p = 0.05). Polyploid fraction (PF): correlation was shown for both overall survival (p = 0.0128) and metastasis-free time (p = 0.0038). CONCLUSION: There is correlation between p53 overexpression and metastatic potential and there is a significant relationship between SPF and PF value and prognosis (metastasis-free and overall survival) of head and neck cancer.

Reoperations after cochlear implantation.

During the 14-year history of cochlear implantation at Semmelweis University, 95 implantations were performed. There were 15 reoperations, and 2 patients had been operated 3 times. All of the reoperated patients received round window or intracochlear MedE1 devices. Successful reinsertion of the electrode was performed without significant difficulty, though in some cases osteoneogenesis was found in the round window or in the scala tympani. None of the patients suffered any inner ear abnormalities due to the first implant, and even the patient with a third implant in the same ear had excellent results and obtained better discrimination scores with the new device. In the authors' opinion, on the basis of the accumulated experience of nearly 100 implantations and 15 reoperations, replacement of the early generation extracochlear implants is most advisable and can be accomplished without adverse effects.

Cyclic GMP and outer hair cell electromotility.

The aim of this study is to examine the effect of phosphorylation pathways on the electrically evoked fast motile response of isolated outer hair cells (OHCs). Transcellular electrical stimulation was applied in the microchamber to guinea pig OHCs and motility was measured before and after drug application. Forskolin (adenylate cyclase activator), phorbol 12-myristate 13-acetate (PMA, protein kinase C activator) and dibutyryl 3',5'-cyclic guanosine monophosphate (cGMP agonist) were studied. As controls, L15 medium and dimethyl-sulfoxide (DMSO) were used. In each group, 12 cells were measured. Forskolin and PMA were dissolved in 0.1% DMSO to render them membrane permeable. DMSO by itself caused a statistically significant electromotility magnitude decrease. Forskolin and PMA could not reverse the motility decrease due to DMSO, the effects seen in their presence were the same as observed with DMSO alone. Thus, neither 3',5'-cyclic AMP-dependent protein kinase nor calcium/phospholipid-dependent protein kinase appear to have modulatory effects on electromotility. Dibutyryl cGMP (DBcGMP), in concentrations of 200 microM, elicited a significant electromotility magnitude increase. The DBcGMP effect could be inhibited by co-application of 200 microM DBcGMP and 100 microM 8-Rp-pCPT-cGMPS (8-4-chlorophenylthio-guanosine 3',5'-cyclic monophosphothioate, Rp isomer, a cGMP antagonist). Our results suggest that OHC electromotility is modulated by a cGMP-dependent pathway.

Cochlear implantation influences contralateral hearing and vestibular responsiveness.

A cochlear implant program has been carried out at the ORL Clinic of Semmelweis University in Budapest since 1985. Different devices and techniques have been used in pre- and postlingual children and adults. Over the last 6 years contralateral hearing improvement has been observed in 18 patients. This phenomenon can usually be demonstrated 6 months after the operation. Since our first observation several other authors have confirmed this phenomenon. However, the underlying mechanism is still obscure; both the efferent innervation and the plasticity of the brain may be important factors. The vestibular function of cochlear implant candidates was checked routinely pre- and postoperatively and changes in vestibular responsiveness were observed. Over the last 3 years air-caloric stimulation has been performed by means of a computer-based ENG system. In most patients the vestibular function was unchanged after the implantation. but in some cases a significant improvement in vestibular responsiveness was noted. Here we briefly describe cases of re-implantation carried out at the clinic. All the patients obtained better speech discrimination scores after having been implanted with intracochlear devices. None of the patients suffered any inner ear abnormality due to the first implant.

Overview of our 13-year-long experience with cochlear implants.

Authors give account of their 13-year-old experience of cochlear implantation. Their results with different devices as well as some observations regarding fitting and rehabilitation are also discussed.

[Diagnostic value of tumor markers in ENT oncology]. / A tumormarkerek diagnosztikus értéke a fül-orr-gégészeti onkológiában.

Control serum samples of young, healthy volunteers (N = 5) were compared with serum samples and laryngeal cancer extracts of patients (N = 12) with stage 3 and 4 cancers. Eight patients were primarily treated by total laryngectomy, 4 patient by palliative irradiation therapy (60 Gy). Ethanol (80%, pH 2) extracts of sera and cancer specimen were gel chromatographed, and the nominally 0.3-5 KDa molecular mass substances were further examined by analytical capillary isotachophoresis (ITP) (LKB. Sweden). Serum samples were also examined after surgery of irradiation therapy. Serum and tumor extracts of each laryngeal cancer patient contained a substance in the molecular mass range of 0.3-5 kDa. This was not detected in the serum of normal control subjects. The marker-candidate substance disappeared from the serum of four out of 8 laryngectomized patients who live tumor-free for years. Recurrence or lymph node metastasis developed in three of the remaining four patients who did not become free of the marker substance after laryngectomy. The concentration of the marker has been increased in the serum after palliative irradiation in all four patients. This marker substance is probably a product of tumor necrosis. The marker may adequately monitor the recurrence of tumor postoperatively of after irradiation therapy.

Comparative results with different cochlear implants.

The cochlear implant program in Budapest began in 1985, since when 60 operations have been performed, 14 of them on children (51 primary procedures and 9 reimplantations). Different devices and also different techniques have been used: extracochlear promontory, extracochlear round window and intracochlear implants. Various speech processors were applied; at first a digital pulsatile sound-encoding system, later on analog processors were used, while processors operating on the basis of the CIS strategy are preferred nowadays. The operations were performed on both pre- and postlingual patients. In several cases contralateral hearing improvement was observed 6 months after the operation. Considerable experience has been gained of unique cases, such as a deaf-blind prelingual child and prelingual twins. Evaluating cochlear implant performance, in addition to the usual audiological tests measuring postoperative speech understanding, warble tone sound field thresholds were also established.

Laser surgery of the vocal cord.

A total of 1032 vocal cord operations have been performed by means of CO2 laser in the Department of Otorhinolaryngology, Head and Neck Surgery of the Semmelweis University of Medicine in Budapest in the past 10 years. There were 687 benign cases and 345 malignant cases of lesions discovered. The procedures were performed under general anesthesia in many instances with jet narcosis--in laryngomicroscopic exposure. The operations were preceded by careful objective diagnostics, such as videolaryngostroboscopy, fiberoscopy, voice analysis, airflow and resistance measurements, while the voice and breathing functions were monitored postoperatively. Our policy in the therapy of the benign lesions was always to use a minimally invasive technique, avoiding damage to the anterior commissure, the vocal ligament and the subglottic space. We have experienced a 3-year survival rate in 87% of the patients with vocal cord carcinomas. According to the results of the past 10 years it is proven that the CO2 laser technique is an efficient method as well in the surgery of the benign and malignant vocal cord lesions, as in the bilateral vocal cord paralysis. Laser surgery might also prevent malignant transformation in precancerous vocal cord diseases.

Search for prognostic factors in head and neck cancer.

Fifteen patients with head and neck carcinoma were treated with irradiation (14-70 Gy telecobalt). Apoptotic and mitotic index, DNA index, ratio of cells in S phase, p53 protein overexpression in untreated tumours as well as the changes of these parameters after the first 2 Gy irradiation except proliferative kinetics parameters were examined in order to determine the prognostic value of these factors. The data show that inducibility of apoptosis is very low in head and neck carcinomas which correlate with the unfavourable prognosis. The decrease in mitotic index after the first 2 Gy irradiation, which occurred in 7 cases--5 of them still alive--indicates a better chance for relatively longer survival. In immunohistochemically p53 positive tumours frequently occurring aneuploidy and elevated S-phase rate were found.

Evaluation of performance with the COMBI40 cochlear implant in adults: a multicentric clinical study.

The present multicentric clinical study involves 19 centres, 16 of them in German-speaking countries, 1 British, 1 Polish and 1 Hungarian. 60 postlingually deafened adults with a mean age of 47.5 years (20-70) and mean duration of deafness of 5.3 years (0.5-20) have been evaluated with the MED-EL COMBI 40 cochlear implant which implements a high-rate continuous-interleaved-sampling strategy with 8 channels. Safety and effectiveness data have been collected. Speech perception tests include a 16-consonant, an 8-vowel, a sentence and a monosyllabic-word test in all languages and a 2-digit figure test in all languages but English. Test intervals are 1, 3, 6 months and 1 year after first fitting. 41 of the 60 postlingually deafened adult study patients have completed their 6-month evaluation. While their pre-operative monosyllabic-word score was 0%, their mean monosyllabic-word score 6 months after first fitting was 48% (8-90) with a median of 50%. The mean sentence understanding was 84% (24-100) with a median of 90%. The respective values for the 1-year evaluations with 25 patients are a mean of 50% (5-85), with a median of 60% for the monosyllables and a mean of 89% (30-100), with a median of 97%, for the sentences.

[Etiology, investigation and therapy of facial nerve palsy]. / A nervus facialis perifériás bénulásának okairól, vizsgálatáról és kezeléséról.

The authors give a description of the causes of the peripheral facial palsy (traumas, viral and bacterial infections, tumors and palsies of unknown origin). Emphasis is given to those anamnestic data, which are useful in the differential diagnostic procedure. Diagnostic methods (modern otologic investigation technics, imaging methods, electrodiagnostic tests), which may help in the precise diagnosis, are discussed. Authors survey the guidelines in the medical and surgical treatment, as well as the electrotherapy of the peripheral facial palsy. The prognostic factors of the disease are also discussed. The author's opinion, that the effectiveness of the treatment is good, and consequently to treat the patients is necessary, and gives high success rate to the doctor.

[Cochlear implants]. / A cochlearis implantáció.

Cochlear implantation is a method of utmost importance recently employed in ear surgery. It makes even speech understanding possible with electrical stimulation of the inner ear in case of bilateral total deafness of cochlear origin. The authors have performed cochlear implantation for 10 years at the Ear-Nose and Throat Clinic of Semmelweis University. Since 1985 different implantation techniques have been used in case of 58 patients, both adults and children. The authors give account of of technical details, rapidly changing selection criteria and the call attention to the problems of peri- and postoperative period and rehabilitation, on they basis of their own results. Importance of team-work of the ear-surgeon, audiologist, psychologist, physicist and speech-therapist is emphasized, because success of the operation is based on proper selection, skillful operating techniques and postoperative rehabilitation, as well.

Otoacoustic emissions: a new tool for monitoring intracranial pressure changes through stapes displacements.

Changes in hydrostatic intracranial pressure (ICP) are thought to be transmitted to cochlear liquids, thereby altering the mechanical load on the stapes footplate. Hence the stiffness of stapes' annular ligament is expected to reflect ICP changes. Corresponding middle-ear transmission changes have been assessed using click-evoked otoacoustic emissions (EOAE) in two experiments. The first one was performed in 22 normal human subjects submitted to posture changes. In the second one, controlled ICP increases were applied to 18 patients in neurosurgery operating theater. EOAEs were monitored in these subjects throughout the experiments and their phases and amplitudes were analyzed as a function of frequency. ICP affected EOAEs in a systematic manner in both experiments, i.e., the main effect of ICP increase was phase lead of EOAE components below 2 kHz without any significant amplitude or frequency shift. Their variations were much more evident than the modifications in middle-ear impedance assessed by standard impedance or admittance measurements. The second experiment led to a quantitative linear relationship between ICP and EOAE phases. It demonstrated that the sensitivity of EOAE phase monitoring technique proves to be quite high, i.e., 55 daPa increases in ICP are readily detected in all subjects. The results are consistent with the predictions of classical middle-ear models as to the transmission alterations induced by ICP-related changes in the stiffness of the annular ligament of the stapes. Non-invasive monitoring of ICP in patients with hydrocephalus treated with ventriculo-peritoneal shunts might be attempted with this technique, although it is restricted to patients with detectable EOAEs (i.e., about 50% in this series).

Cochlear implants in children.

The authors give an account of their experiences with cochlear implants on the basis of 10 years' work. Preoperative evaluation, operating methods and postoperative rehabilitation are presented. During a decade 56 operations were performed, 11 of them on children. Results with prelingually deaf children are demonstrated together with the phenomenon of hearing improvement observed on the contralateral side of the operation.