Challenging a dogma--surgery yields superior long-term results for T1a squamous cell carcinoma of the glottic larynx compared to radiotherapy.

AIMS: The aim of this study was to compare laser surgery, conventional endoscopic surgery and radiotherapy in the treatment of early T1a glottic cancer. METHODS: We conducted a retrospective analysis of patients with early vocal cord cancer (who underwent either conventional surgery via endoscopy or laryngofissur, or primary radiotherapy) at the Medical University of Vienna. By univariate and multivariate Cox regression models the influence of treatment and other parameters on survival and locoregional control were analysed. RESULTS: 337 Patients were analyzed with a mean follow-up period of 133.8 months. Overall survival rates where similar in all three treatment groups. Five-year, 10-year and 15-year estimates of disease specific survival for laser-treated patients were 100%, for conventional surgery were 100%, 98% and 98%, and for radiotherapy were 96%, 92% and 91%, respectively. Locoregional recurrences were observed after laser surgery in 10%, after conventional surgery in 13% and after radiotherapy in 30% of the patients treated. According to the log-rank test, time to relapse was significantly shorter for irradiated patients compared to patients who underwent surgery (p < 0.0001). Mortality caused by the laryngeal tumour was significantly higher in the radiotherapy group (p = 0.003). CONCLUSION: Patients undergoing laser or conventional surgery have a significantly lower incidence of locoregional recurrences and longer disease-free intervals when compared to patients treated by radiotherapy.

Role of substance P in the peripheral vestibular and auditory system.

The central role of substance P (SP) has attracted growing interest in the past two decades. One of the important physiological functions of SP and other tachykinins is that of a neurotransmitter in primary afferent neurons. Recent immunocytochemical, biochemical and electrophysiological investigations on various neurotransmitters support the hypothesis that SP has a similar function in the vestibular and auditory systems of all mammals including humans. The purpose of this review is to give an overview of the distribution and concomitant physiological functions of this peptide in these sensory systems.

Skin test results but not serology reflect immediate type respiratory sensitivity: a study performed with recombinant allergen molecules.

The diagnosis of type I allergy, an IgE-antibody-mediated hypersensitivity disease affecting more than 25% of the population, is based on the measurement of allergen-specific serum IgE levels and provocation testing. Whether the determination of allergen- specific serum IgE levels can replace in vivo provocation testing for allergy diagnosis is a controversial issue. We used purified recombinant timothy grass and birch pollen allergens to compare by skin prick and nasal provocation testing as well as by serology in vivo sensitivity with antibody-binding capacity in 24 pollen allergic patients and eight control individuals. Results from biologic tests were correlated with each other and with allergen-specific IgE and IgG1-4 levels. IgE-reactive allergens induced immediate skin and nasal reactions, but the intensity of the allergic tissue reactions was not correlated with either the levels of allergen-specific IgE or the levels of allergen-specific IgG antibodies. Less frequently detected allergens with low IgE-binding capacity were able to induce strong allergic reactions comparable to those caused by major allergens with high IgE-binding capacity. In contrast, skin test and nasal provocation results were significantly correlated (r = 0.63, p < 0.01). Our study thus demonstrates on a molecular level that skin testing provides a better reflection of immediate type respiratory sensitivity than serologic measurements. These results have implications for allergy diagnosis and, in particular, for the selection of relevant allergen components for specific immunotherapy.

Scaling-violation phenomena and fractality in the human posture control systems.

By analyzing the movements of quiet standing persons by means of wavelet statistics, we observe multiple scaling regions in the underlying body dynamics. The use of the wavelet-variance function opens the possibility to relate scaling violations to different modes of posture control. We show that scaling behavior becomes close to perfect, when correctional movements are dominated by the vestibular system.

[Intraoperative navigation in paranasal sinus surgery with the Philips "Neuroguide" system]. / Intraoperative Navigation in der Nasennebenhöhlenchirurgie mit dem Philips "Neuroguide"-System.

OBJECTIVE: To investigate the feasibility, precision and usefulness of computer aided surgery in ENT-sinus surgery. MATERIAL AND METHODS: 5 Patients with chronic sinus pathology and an indication for sinus surgery were elected. For intraoperative navigation we used a Philips "NEUROGUIDE" system and surgical instruments with LED's. Navigation procedures are described in detail in the paper, the system's precision was measured by pointing at anatomical landmarks. The accuracy was measured as the distance in millimeter between the bony structures of the CT scan on screen and the haircross of the pointer's tip on the screen. Another parameter of the systems accuracy was calculated by the system itself as the root mean square error in millimeter (RMSE) between the registered markers position and the marker position in the CT data set. RESULTS: Axial 3/3/1 mm spiral CT provided sufficient resolution, data transfer via optical disk was practicable. Positioning of the navigation equipment required some experience and the registration of the patients head position needed attention, as the markers have to be pointed at precisely. During operation, the head tracking system must not change its position on the patients head to ensure a correct navigation display. The main advantage of the computed navigation system was the constant orientation during the sinus surgical procedure. Frontiers and critical anatomical structures could be identified in the corresponding CT data set, thus enabling the surgeon to decide on the further procedure. At present stage, the operation time was increased through the handling of the navigation system for at about 15 min, resulting in additional time of narcosis. CONCLUSION: We found the computed navigation system Philips "NEUROGUIDE" system to be an established technical aid, ready to use for ENT sinus surgery, in our cases with a precision between 1 and 3 mm. These results were similar to results obtained with a SPOCS Navigation System from Aesculap, as previously published by us [17].

Metabotropic glutamate receptors group I are involved in cochlear neurotransmission.

All three types of ionotropic glutamate receptors, AMPA, NMDA and kainate, contribute to the neurotransmission between inner hair cells (IHC) and afferent neurons in the mammalian cochlea. We used microiontophoretic techniques to investigate whether metabotropic glutamate receptors group I (mGluR I) are also involved in the transmission of IHC afferents of the guinea pig. The mGluR I agonist DHPG produced an increase in afferent firing, which lasted significantly longer than that of the ionotropic agonists AMPA and NMDA. The activation was reversibly blocked by the mGluR I antagonist AIDA in a dose-dependent manner. AIDA also diminished spontaneous activity, but only slightly affected the AMPA- or NMDA-induced firing rate. Our results suggest that mGluR I are involved in peripheral auditory processing.

Stochastic resonance in cochlear signal transduction.

The use of a stochastic resonance model contributes crucially to our comprehension of the intensity resolution characteristics of the mammalian cochlea. In guinea pigs, as demonstrated by different statistical methods, the temporal distribution of the interspike intervals of the spontaneous activity reflects an intrinsic cochlear white noise process, demanded as basic requirement for manifest stochastic resonance phenomena. Brownian motion of cochlear fluids is discussed as the underlying white noise motor. Following our model, the amount of white noise, adjusted at the level of the stereocilia of the inner hair cells, determines the threshold, dynamic range and intensity discrimination limen of an individual afferent neuron of the mammalian cochlea.

New approaches for inner ear therapy with glutamate antagonists.

In the mammalian cochlea neurotransmission between inner hair cells and afferent auditory neurons is probably mediated by glutamate or another related excitatory amino acid. Neurotoxicity induced by excessive glutamate release seems to play a crucial role in some pathological conditions of the cochlea, such as ischaemia or noise trauma. Thus, glutamate antagonists may be a new therapeutic strategy for different inner ear diseases. Because of their potential severe side-effects only a few glutamate antagonists have so far been adopted for clinical use. We used microiontophoretic techniques to compare the effects of memantine and caroverine on the glutamatergic transmission of inner hair cells of the guinea pig and tested the possibility of a local administration of memantine to the cochlea with a micropump. Memantine selectively inhibited the NMDA (N-methyl-D-aspartate) stimulated activity while caroverine blocked NMDA as well as AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) induced activity of inner hair cell afferents. With a flow rate of 1 microl/h the local administration of memantine via a cochleotomy was succeeded in a reversible blockade of the spontaneous and the NMDA induced firing of inner hair cell afferents. These results suggest that local application to the cochlea could be a feasible way to administer glutamate antagonists in sufficient amounts while avoiding systemic side-effects.

Calcium-dependent immunoglobulin E recognition of the apo- and calcium-bound form of a cross-reactive two EF-hand timothy grass pollen allergen, Phl p 7.

Type I allergy, an immunodisorder that affects almost 20% of the population worldwide, is based on the immunoglobulin E (IgE) recognition of per se innocuous antigens (allergens). Pollen from wind-pollinated plants belong to the most potent allergen sources. We report the isolation of a cDNA coding for a 8.6 kDa two EF-hand calcium binding allergen, Phl p 7, from a timothy grass (Phleum pratense) pollen expression cDNA library, using serum IgE from a grass pollen allergic patient. Sequence analysis identified Phl p 7 as a member of a recently discovered subfamily of pollen-specific calcium binding proteins. Recombinant Phl p 7 was expressed in Escherichia coli and purified to homogeneity as determined by mass spectroscopy. Approximately 10% of pollen allergic patients displayed IgE reactivity to rPhl p 7 and Phl p 7-homologous allergens present in pollens of monocotyledonic and dicotyledonic plants. Circular dichroism analysis of the calcium-bound and apo-rPhl p 7 indicated that differences in IgE recognition may be due to calcium-induced changes in the protein conformation. The fact that patients mount IgE antibodies against different protein conformations is interpreted as a footprint of a preferential sensitization against either form. The biological activity of rPhl p 7 was demonstrated by its ability to induce basophil histamine release and immediate type skin reactions in sensitized individuals. In conclusion, IgE binding to Phl p 7 represents an example for the conformation-dependent IgE recognition of an allergen. Recombinant Phl p 7 may be used for diagnosis and perhaps treatment of a group of patients who suffer from allergy to pollens of many unrelated plant species.

GABA(A) receptor modulates the activity of inner hair cell afferents in guinea pig cochlea.

The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is mediated by two main categories of receptors: the GABA(A) and GABA(B) receptor. Recent immunocytochemical and electron microscopical studies revealed the existence of GABA at the efferent olivocochlear innervation of the guinea pig cochlea. In this microiontophoretic study we examined the effect of GABA on spontaneous and glutamate or acetylcholine induced activity of afferent fibres in the dendritic region of inner hair cells. Furthermore, the receptor subtypes being responsible for this GABA action were analysed using specific agonists and antagonists on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) induced activity. The spike activities of the subsynaptic area were recorded in the third or fourth turn of the cochlea of anaesthetised guinea pigs. Application of GABA had little effect on spontaneous activity whereas the glutamate or acetylcholine induced firing rate could be depressed by GABA. AMPA and NMDA induced activity was reduced by the GABA(A) agonist muscimol but not by the GABA(B) agonist baclofen. The GABA(A) antagonist blocked the inhibition of both GABA and the GABA(A) agonist. In contrast, the GABA(B) antagonist saclofen was without effect. These results reveal that GABA reduces the activated firing rate of inner hair cell afferents mediated by the GABA(A) receptor subtype.

Memantine suppresses the glutamatergic neurotransmission of mammalian inner hair cells.

The glutamatergic synapses between inner hair cells and afferent neurons seem to be involved in pathophysiological conditions of the cochlea. The excessive release of glutamate from inner hair cells during noise trauma and ischemia affects the afferent neurons. It is possible that in tinnitus outer hair cell or inner hair cell dysfunction or damage leads to an altered spontaneous release of glutamate from inner hair cells. Thus, the pharmacological modulation of glutamatergic neurotransmission could be of great value in the therapy of certain inner ear diseases. Recently, it has been discovered that the spasmolytic drug memantine has antiglutamatergic properties. As a possible drug for inner ear diseases, we were interested in the action of memantine on the neurotransmission of inner hair cells. With the aid of microiontophoretic techniques we were able to show a strong depressing effect on spontaneous activity as well as on glutamate-induced activity. This effect seems to be mediated by a blockade of N-methyl-D-aspartate (NMDA) receptors as memantine showed a strong inhibiting effect on NMDA-induced activity but not on AMPA-induced activity. These results recommend memantine for the treatment of inner ear diseases, e.g. especially tinnitus.

Experiences in intraoperative computer-aided navigation in ENT sinus surgery with the Aesculap navigation system.

Five patients with chronic sinus pathology and an indication for sinus surgery were selected. For intraoperative navigation, we used Surgical Planning and Orientation Computer Systems (SPOCS) Aesculap navigation software (ISG Technologies, Mississauga, Ontario, Canada) and surgical instruments fitted with light-emitting diodes. Navigation procedures are described in detail in the article. The system's precision was measured by pointing at anatomical landmarks. The accuracy was measured as the distance in millimeters between the bony structures of the computed tomographic (CT) scan on screen and the cross-hair of the pointer tip displayed on the screen. Another parameter of the system's accuracy was calculated by the system itself as the root mean square error in millimeters between the markers' position as registered and their position in the CT data set. Axial 3/3/1-mm spiral CT provided sufficient resolution, and data transfer via optical disk was practicable. Positioning of the navigation equipment required some experience, and the registration of the patient's head position also needed attention, as the markers have to be pointed at precisely. During the operation, the position of the head-tracking system on the patient's head must remain unchanged to ensure a correct navigation display. The main advantage of the computed navigation system was the constant orientation provided during the sinus surgical procedure. Borders and critical anatomical structures could be identified in the corresponding CT data set, thus enabling the surgeon to decide on subsequent procedures. Use of the navigation system was found to increase the operation time by about 1 h, resulting in additional time under anesthesia. We found the SPOCS Aesculap computed navigation system to be an established technical aid, ready for use in ENT sinus surgery. In the cases reported here, a precision between 1 and 3 mm was obtained.

Dopamine regulates the glutamatergic inner hair cell activity in guinea pigs.

Recent immunocytochemical and biochemical studies support a possible neurotransmitter function of dopamine (DA) in the efferent olivocochlear innervation of the guinea pig cochlea. However, the physiological role of DA in cochlear neurotransmission remains unknown. In the present study microiontophoretic techniques were used for testing the action of DA as well as D1- and D2-agonists and -antagonists on spontaneous and N-methyl-D-aspartic acid (NMDA)-, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-, kainic acid- or glutamate-induced firing of afferent fibres in the dendritic region of inner hair cells. Subsynaptic spike activities of anaesthetised guinea pigs were recorded after exposing the third or fourth turn of the cochlea for electrode penetration. Application of DA alone had very little effect on the spontaneous afferent firing rate. In contrast, firing induced by NMDA or AMPA could be depressed by additional administration of DA in a dose-dependent manner. A similar reduction of the induced spike activity was seen after co-administration of D1- or D2-agonists. The action of DA on glutamate agonist-induced firing could be blocked by D1- as well as D2-antagonists. These results show that DA can depress the activated firing rate of the afferent fibres and that this action is mediated by both D1- and D2-receptor subtypes.

Cochlear implant deep electrode insertion: extent of insertional trauma.

We have recently undertaken deep insertions of the Combi-40 cochlear implant electrode (Med-E1 Corp., Innsbruck, Austria) into apical regions of the scala tympani using a cochleostomy approach. In order to examine the extent of the insertional trauma, 12 fresh human temporal bones were implanted with original Combi-40 electrodes. The specimens were histologically processed with the implants in place by employing a sawing and grinding technique. In most cases, only very discrete distortions of the epithelium of the spiral ligament occurred within the middle cochlear turns. Furthermore, a slight displacement of the basilar membrane caused by the electrode was occasionally seen. However, in 2 cases more severe damage such as basilar membrane rupture and electrode displacement was found. Attempts to insert the electrode beyond the point of first resistance resulted in electrode kinking within the basal cochlear turn with subsequent fracture of the osseous spiral lamina. According to our results, deep electrode insertions do not aggravate the insertional trauma provided no force is applied when resistance is felt.

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.

Caroverine in tinnitus treatment. A placebo-controlled blind study.

This study was performed to examine whether a single infusion of caroverine, a quinoxaline-derivative, can be used successfully in the treatment of inner ear tinnitus. Microiontophoretical experiments in guinea-pigs have shown that caroverine acted as a potent competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazone-proprionic acid (AMPA) receptor antagonist and, in higher dosages, a non-competitive N-methyl-d-aspartate (NMDA) antagonist. According to our working hypothesis of the pathophysiology of inner ear tinnitus (cochlear-synaptic tinnitus), these forms of tinnitus occur when the physiological activity of the NMDA and AMPA receptors at the subsynaptic membranes of inner hair cell afferents is disturbed. In total, 60 patients with inner ear tinnitus of assumed cochlear-synaptic pathophysiology were included in the study: after computerized randomization, 30 were treated with caroverine and 30 with placebo. For a response to have occurred, tinnitus had to show a reduction in both subjective rating and psychoacoustic measurement (tinnitus matching). In the caroverine group, 63.3% responded to therapy immediately after the infusion. In the placebo group, none of the patients treated showed a significant response according to the defined success criteria. The results confirm our working hypothesis on the genesis of cochlear-synaptic tinnitus.

[Late functional outcome after reconstruction of the upper aerodigestive tract with free transplanted microvascular anastomosed jejunum]. / Funktionelle Spätergebnisse nach Wiederherstellung der oberen Atem- und Schluckwege mit frei transplantiertem mikrovaskulär anastomosiertem Jejunum.

Since 1983, 90 autologous jejunal transplantations for reconstruction of the upper digestive tract have been performed in 89 patients (9 females, 80 males, average age 56.3 years). 73 patients were operated primarily, in 16 patients a recurrent tumor had been treated. One patient received a second jejunal graft after necrosis. In these heterogenous patients, the primary tumor was located in the hypopharynx 48 times, in the larynx 21 times, in the oropharynx 19 times and twice in the oral cavity. There was nearly always tumor stage III or IV without distant metastases. Following locoregional tumor resection, speech restoration was achieved 35 times by a siphon-like tube, and the upper digestive tract was reconstructed using a patch 18 times and by a tube 28 times. A combination of tube or patch with a siphon-like tube was employed 9 times. In only two of 16 patients with recurrent tumor, speech reconstruction was performed, in the other 14, the upper digestive tract was reconstructed. In those patients, in whom speech reconstruction (by siphon tube or by combination with tube/patch) was intended, this was achieved in 81.5%. Successful functional reconstruction of the upper digestive tract (by patch, tube, combination) could be achieved in about 60% of these patients.

Substance P in the auditory hair cells in the guinea pig.

Previous immunohistochemical and electrophysiological studies on various neurotransmitters revealed the tachykinin substance P (SP) as a neuromodulator in the auditory system of mammals. This study was performed in order to determine the immunohistochemical expression and distribution pattern of SP in the organ of Corti, especially in the inner (IHC) and outer hair cell (OHC) region of the guinea pig. We examined the immunoreactivity of SP of surface preparations by means of a fluorescence and a laser scanning microscope. The electrophysiological action of SP, N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were recorded at the subsynaptic afferent region of the IHCs using micro-iontophoretic techniques. The SP-like immunostaining could be detected at the basal and apical pole of the IHCs with a gradient distribution pattern from the basal to the apical turn. Furthermore, we could demonstrate SP-like immunoreactivity in OHCs with different occurrence in turns as well as in rows. Electrical activity was induced by applying SP, NMDA and AMPA perisynaptically to the IHCs. The selective SP antagonist spantide (D-Arg1, D-Trp7,9, Leu11-substance P) specifically blocked the SP-induced activity but without altering the activity of NMDA and AMPA. In contrast, specific NMDA or AMPA antagonists reversibly blocked either the NMDA- or AMPA-induced responses without affecting the SP-induced activity. These immunohistochemical and electrophysiological results confirm that SP may represent a neuromodulator function at the synapses of the IHCs in the guinea pig.

Speech understanding in quiet and in noise with the CIS speech coding strategy (MED-EL Combi-40) compared to the multipeak and spectral peak strategies (nucleus).

This study compares sentence understanding in quiet and in noise with 3 different speech coding strategies for cochlear implants. The results show that the spectral-peak (SPEAK) and continuous-interleaved-sampling (CIS) coding strategies, based on spectral signal analysis, allow for better speech understanding in quiet as well as in noise, than the multipeak (MPEAK) coding strategy, which relys on speech feature extraction. In the intrasubject comparison of the MPEAK and SPEAK strategies, the SPEAK coding strategy provided a considerable improvement in quiet and in noise for the majority of patients using the Nucleus 22 Mini-implant. In the intersubject comparisons, the mean results in noise with the CIS strategy were superior to both the MPEAK and the SPEAK strategies. The difference was greatest for the most difficult tests in noise. Understanding in noise was least reduced for the CIS strategy. Understanding in quiet was not significantly different between the CIS and the SPEAK strategies; both strategies were significantly better than the MPEAK strategy in quiet. These results are still preliminary, due to the relatively small number of patients and the great inherent intersubject variability of results.