The role of the different neoglottis forms in the development of esophageal voice.

UNLABELLED: Evaluation of voice quality parameters of esophageal speech in different neoglottis forms after total laryngectomy. METHODS: Presentation of voice analysis of 20 patients, who underwent total laryngectomy. The success of acquiring this technique was estimated by means of a voice analyzing program (pitch, sound-holding, loudness, spectrogram),and by the intelligibility via the telephone. Shape of the different types of neoglottis that developed and its functioning during vocalization and continuous speech were observed by nasal endoscopy. Data obtained from the voice analysis were compared among the observed three different neoglottis forms. RESULTS: The average dysphonia index of the 20 patients was 1.67 ± 0.38 (mean ± SD). Nasal fiberoscopic examination revealed three different types of neoglottis forms ­ a small mucosal button, two mucosal battens, and a mucosal lip. Voice quality of the esophageal speech of the patients with the mucosal button was found to be the closest to normal by subjective and objective acoustical evaluation. CONCLUSIONS: These findings emphasize the importance of the proper wound closure technique which can facilitate the development of a special button shape neoglottis form and help to acquire esophageal speech with the best quality parameters shortly after total laryngectomy.

Dendrodendritic connections between the cochlear efferent neurons in guinea pig.

The outer hair cells of organ of Corti are innervated by the efferent neurons of medial olivocochlear neurons (MOC) of the brainstem which modify the cochlear auditory processing and sensitivity. Most of the MOC neurons are excited by a dominant ear and only a small portion of them is excited by both ears resulting in a binaural facilitation. The functional role of the feedback system between the organ of Corti and the cochlear efferent neurons is the protection of the ear from acoustic injury. The rapid impulse propagation in the bilateral olivocochlear system is suggestive of an electrotonic interaction between the bilateral olivocochlear neurons. The morphological background of the MOC pathway is not yet completely characterized. Therefore, we have labeled the bilateral cochlear nerves with different neuronal tracers in guinea pigs. In the anesthetized animals the cochlear nerves were exposed in the basal part of the modiolus and labeled simultaneously with different retrograde fluorescent tracers. By using confocal laser scanning microscope we could detect close appositions between the dendrites of the neurons of bilateral MOC. The distance between the neighboring profiles suggested close membrane appositions without interposing glial elements. These connections might serve as one of the underlying mechanisms of the binaural facilitation mediated by the olivocochlear system.

Retropharyngeal superficial angiomyxoma.

OBJECTIVE: To describe the first published case of superficial angiomyxoma with an epithelial component occurring in the retropharynx. METHOD: Case report of a patient with swallowing difficulties caused by a rare case of superficial angiomyxoma in the retropharynx. RESULTS: Superficial angiomyxoma is a distinct entity among the dermal myxomatous lesions. Superficial angiomyxoma is poorly circumscribed, and local recurrence is common unless the tumour is excised with clear margins. Distinctive histological features include a myxoid mass composed of spindle and stellate-shaped cells and occasional multinucleated cells. There is prominent vasculature and a mixed inflammatory infiltrate in the stroma, particularly by neutrophil polymorphs. Epithelial structures are seen in about one-third of cases. A case of retropharyngeal tumour with morphological features of superficial angiomyxoma is reported. The tumour cells, including multinucleated ones, were negative for soft tissue differentiation markers. The inflammatory cells included lymphocytes, histiocytes and neutrophil polymorphs. CONCLUSION: This case demonstrates that a cutaneous type of angiomyxoma with epithelial-lined structures can occur in deep soft tissue, such as the retropharynx.

Recurrent laryngeal nerve paralysis due to subclinical Lyme borreliosis.

OBJECTIVE: We report an extremely rare case of recurrent laryngeal nerve paralysis due to subclinical Lyme borreliosis. METHOD: Case report presenting a 15-year-old girl referred with hoarseness and soft voice. RESULTS: Right-sided recurrent laryngeal nerve paralysis was observed using videolaryngoscopy. Imaging was used to exclude intracranial, cervical and intrathoracic embryological lesions, vascular malformations and tumours. Laboratory and electrophysiological investigations were used to exclude inflammatory and paraneoplastic processes, endocrinopathy and metabolic disorders. Serological testing was positive for Lyme disease. Parenteral ceftriaxone therapy was commenced. The patient's nerve paralysis showed complete recovery on the seventh day of antibiotic treatment; this was confirmed by videolaryngoscopy. CONCLUSION: Recurrent laryngeal nerve paralysis is an extremely rare complication of neuroborreliosis associated with Lyme disease. In patients with recurrent laryngeal nerve paralysis in whom the clinical history is uncertain and the usual diagnostic methods give negative results, screening with anti-borrelia immunoglobulin M is suggested.

High co-prevalence of genogroup 1 TT virus and human papillomavirus is associated with poor clinical outcome of laryngeal carcinoma.

BACKGROUND: The aetiology and factors leading to the progression of laryngeal cancer are still unclear. Although human papillomavirus (HPV) has been suggested to play a role, reports concerning the effect of HPV infection on tumour development are controversial. Recently, transfusion transmitted virus (TTV) was suggested to play a role in certain infections as a causative or coinfecting agent. AIMS: To investigate whether the development and progression of laryngeal squamous cell carcinoma is associated with coinfection with TTV and HPV. METHODS: The prevalence of TTV and HPV was investigated using the polymerase chain reaction in tissue samples from 40 healthy individuals, 10 patients with recurrent papillomatosis, five patients with papillomatosis with malignant transformation, and 25 patients with laryngeal carcinoma. The obtained prevalence data were compared and analysed statistically. RESULTS: In the 11 patients with carcinoma who had metastasis or relapse there was a high rate of coinfection with genogroup 1 TTV and HPV (eight of 11), whereas in the 14 without tumour progression no coinfection was found. Coinfection was associated with significantly lower tumour free survival in patients with carcinoma (p < 0.001). Furthermore, four of five patients who had papillomatosis with malignant transformation were coinfected with genogroup 1 TTV and HPV. CONCLUSIONS: Although the nature of cooperation between HPV and TTV needs to be investigated further, coinfection with genogroup 1 TTV and HPV appears to be associated with poor clinical outcome in laryngeal cancer.

The characteristics of human papillomavirus DNA in head and neck cancers and papillomas.

AIM: To determine the prevalence, type, physical state, and viral load of human papillomavirus (HPV) DNA in cases of head and neck cancer and recurrent respiratory papillomatosis (RRP). METHODS: The prevalence and type of HPV DNA was determined in 27 fresh frozen tissue specimens from patients with head and neck cancers and 16 specimens from 10 patients with RRP by MY09/MY11 and GP5+/GP6+ nested polymerase chain reaction (PCR) and subsequent restriction enzyme cleavage. The physical state of HPV DNA was analysed by E1, E2, and E1E2 specific PCRs and Southern blot hybridisation (SBH). RESULTS: HPV DNA was detected in 13 of 27 cancers and 10 of 10 papillomas. Both low risk HPV-6 and HPV-11 and high risk HPV-16 were present in cancers in low copy numbers, whereas papillomas exclusively harboured low risk HPV-6 and HPV-11. E1E2 PCRs failed to determine the physical state of HPV in cancers except one case where HPV-6 DNA was integrated. In contrast to cancers, all papillomas showed the episomal state of HPV DNA and a relatively higher viral load. CONCLUSIONS: Based on the prevalence, type, physical state, and copy number of HPV DNA, cancers and papillomas tend to show a different HPV DNA profile. The 100% positivity rate of low risk HPV types confirms the role of HPV-6 and HPV-11 in the aetiology of RRP.

[Phenotypic characterization of a DFNA6 family with low-frequency hearing loss]. / Phänotypische Charakterisierung einer DFNA6-Familie mit Tieftonschwerhörigkeit.

BACKGROUND: Hereditary hearing impairment is a heterogeneous sensory defect with approximately two-thirds of all cases being nonsyndromic. Only two loci (DFNA1 and DFNA6/14/38) are associated with low frequency sensorineural nonsyndromic hearing impairment. DFNA6 was mapped to chromosome 4p16. Recessive mutations in the WFS1 gene are responsible for Wolfram syndrome; missense mutations inherited as an autosomal dominant result in low frequency sensorineural hearing impairment (LFSNHI). PATIENTS AND METHODS: In this study we analyzed the phenotype of a large Hungarian family with LFSNHI and linkage to DFNA6. The family contains 14 affected persons. RESULTS AND CONCLUSION: In general, these patients show a postlingual, sensorineural, bilateral, symmetric, nonsyndromic low frequency hearing impairment with a slow progression. This impairment is accompanied by normal vision and normal vestibular responses.

Lymphangioma of the sphenoid sinus.

Lymphangiomas are rare benign lymphatic tumours found predominantly in the head and neck region. A case of a cavernous lymphangioma isolated to the sphenoid sinus is described. The authors emphasize the extreme rarity of the isolated sphenoid lymphangioma, as to their knowledge this is the first report in the English literature.

[The effects of auditory research on clinical practice]. / Auswirkungen der Hörforschung auf die klinische Arbeit.

Recent research has shown that only the inner hair cells pass information on to the brain while the outer hair cells serve as an active amplifier and thus stimulate the inner cells. The electromotility of the outer hair cells is very vulnerable. If it is lacking, sensorineuronal hearing loss occurs. Substances, that compete for the chloride combining site of the motor protein prestin, such as salicylate, might have a blocking effect on the regulation of electromotility. On the other hand, the control of the intracellular Ca(2+) level and the intracellular combination of ions in the outer hair cells might protect their electromotile properties against damage caused by harmful substances (ototoxic drugs) or mechanisms (exposition to noise), which would otherwise lead to irreversible sensorineuronal hearing loss. This is because an increase in the intracellular Ca(2+) level activates phosphorylating enzymes. Thus the stiffness of the outer hair cells is reduced, causing an increase in electromotility.

[Phenotype of patients showing hearing impairment based on the 35delG mutation in the connexin 26 gene]. / Phänotypische Charakterisierung schwerhöriger Patienten mit homozygoter 35delG-Mutation im Connexin-26-Gen.

BACKGROUND: Hereditary hearing impairment constitutes a heterogeneous class of disorders showing different patterns of inheritance and involving multiple genes. Mutations in the GJB2 gene, especially the 35delG mutation, have been established as a major cause of inherited and sporadic nonsyndromic hearing impairment in different populations. METHODS: We analyzed 14 northeast Hungarian families and 69 sporadic cases with nonsyndromic hearing impairment for the 35delG mutation. Sixty-five patients showing a homozygous 35delG mutation were examined regarding their audiologic phenotype. RESULTS: In general, these patients (70%) showed a prelingual, sensorineural, bilateral, symmetric hearing impairment without progression. The audiograms demonstrated sloping as well as flat patterns. CONCLUSIONS: The severity of hearing impairment varied in 30% of all analyzed patients, making genetic counseling difficult.

Ionic currents determining the membrane characteristics of type I spiral ganglion neurons of the guinea pig.

Enzymatically isolated type I spiral ganglion neurons of the guinea pig have been investigated in the present study. The identity of the cells was confirmed by using anti-neuron-specific enolase immunostaining. The presence and shredding of the myelin sheath was also documented by employing anti-S100 immunoreaction. The membrane characteristics of the cells were studied by using the whole-cell patch-clamp technique. The whole-cell capacitance of the cells was 9 +/- 2 pF (n = 51), while the resting membrane potential of the cells was -62 +/- 9 mV (n = 19). When suprathreshold depolarizing stimuli were applied, the neurons fired a single action potential at the beginning of the stimulation. It was confirmed in this study that type I spiral ganglion cells possess a hyperpolarization-activated nonspecific cationic current (Ih). The major characteristics of this current component were unaffected by the enzyme treatment. Type I spiral ganglion cells also expressed various depolarization-activated K+ current components. A high-threshold outward current was sensitive to 1-10 mm TEA+ application. The ganglion cells also expressed a relatively small, but nevertheless present, transient outward current component which was less sensitive to TEA+ but could be inhibited by 100 micro m 4-aminopyridine. A DTX-I-sensitive current was responsible for some 30% of the total outward current (at 0 mV), showed rapid activation at membrane potentials positive to -50 mV and demonstrated very little inactivation. However, inhibition of the highly 4-AP- or DTX-I-sensitive component did not alter the rapidly inactivating nature of the firing pattern of the cells.

Changes in brain activation caused by caloric stimulation in the case of cochleovestibular denervation--PET study.

There are a number of well-known stimulation methods for the investigation of the central projection of the vestibular system. In addition to optokinetic, galvanic and neck vibration tests, the most widespread method is caloric stimulation. These listed methods cause not only vestibular, but also other effects on the central nervous system (CNS) (acoustic, tactile and nociceptive). In this paper, positron emission tomography (PET) was used to investigate whether caloric stimulation contains a non-vestibular (extravestibular) component, which would cause a distortion in the cortical activity and therefore in the vestibular effect on the CNS. Caloric stimulation was carried out in six patients who had been operated on due to cerebello-pontine angle tumour. These patients suffered post-operatively from a complete lesion of the vestibular system and anacusis on the operated side. Ipsilaterally activated areas were the inferior pole of the post-central gyrus and temporoparietal junction, caudal part of the post-central gyrus (SI, SII), inferior parietal lobule and medial frontal gyrus. Contralaterally activated areas were the anterior cingulate gyrus, medial frontal gyrus, posterior part of the insula, post-central gyrus and temporoparietal junction (SII). Ipsilaterally deactivated areas were the caudal and cranial part of the medial occipital gyrus (V2, V3, V4, V5). Contralaterally deactivated areas were the lingual gyrus, inferior occipital gyrus (V2, V3) and fusiform gyrus. On the basis of these data, it was postulated that, during caloric stimulation, extravestibular reaction also occurs, which corresponds to the subjective feeling of heat and pain. The deactivation of the occipital cortex due to an extravestibular effect was demonstrated. This is the first observation to suggest the possibility of nociceptivevisual interaction.

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.

Frequency of the recessive 30delG mutation in the GJB2 gene in Northeast-Hungarian individuals and patients with hearing impairment.

Mutations in the GJB2 gene, which encodes a gap junction protein (connexin 26) account for up to 50% of cases of congenital autosomal recessive non-syndromic hearing impairment. A single mutation, 30delG, is responsible for 70% of this autosomal recessive hearing loss in Europe. This study describes the 30delG mutation analysis of 23 Hungarian families (64 individuals) with at least two subjects with congenital non-syndromic hearing defect and of 52 unrelated individuals from the Northeastern population of Hungary. In all patients, non-progressive hearing impairment varied from moderate to profound involving all frequencies. DNA was tested by PCR based restriction enzyme assay (BSiYI). Sixty-four percent of the patients displayed this one base deletion in GJB2. Out of these, 65.9% were homozygous for this mutation and 34.1% were heterozygotes. The latter showed compound heterozygosity since in these 14 patients, eight previously reported different nucleotide changes were observed on the second allele. The carrier frequency of the 30delG mutation among control group was one in 10.4 (9.6%). This high frequency of 30delG corresponds more to frequencies reported in Southern than in North Europeans.

[Processing vestibular impulses in the central nervous system. Study based on positron emission tomography]. / Verarbeitung vestibulärer Impulse im Zentralnervensystem. Untersuchung anhand der Positronen-Emissions-Tomographie.

BACKGROUND AND OBJECTIVE: Functional imaging methods have opened new perspectives for vestibular research. Many authors have investigated the central connections of the system, but the differences between the reports leave further questions open. We investigated the cerebral projection of the vestibular system, using positron emission tomography in right-handed subjects. PATIENTS AND METHODS: Bilateral caloric stimulation was used in every volunteer (n = 6). This can be considered a standard method, which will make it possible to compare the results from different laboratories in the future. A detailed map of activated and deactivated brain regions is included. RESULTS: Changes caused by vestibular stimulation are portrayed. The activated regions partially correspond with previous results in the literature. We would like to point out the Brodmann 6 region as the cortical manifestation of involuntary isometric tightening of muscles. We have found many, previously unidentified regions showing decreased regional cerebral blood flow. CONCLUSIONS: We are the first to point out the functional connection between the hippocampus and the vestibular system in this report.

Phosphorylation mediates the influence of acetylcholine upon outer hair cell electromotility.

Isolated guinea-pig outer hair cells (OHCs) (n = 52) were inserted into a partitioning microchamber and electromotility was measured by a calibrated optoelectronic apparatus. Acetylcholine (ACh), and ACh together with different protein kinase inhibitors, were applied to OHCs through a puffer pipette. ACh produced a magnitude increase of electromotility. This magnitude increase was inhibited by co-application of KN-62, a calcium/calmodulin-dependent protein kinase II (CAMKII) inhibitor. Simultaneous application of ACh and H-89, a selective protein kinase A (PKA) inhibitor, did not antagonize the ACh response. Further support for the CAMKII-mediated ACh influence on electromotility is that the magnitude increase is also inhibited by the calmodulin antagonist trifluoperazine (TFP) and by the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) inhibitor thapsigargin. The results suggest an essential role of calcium in the ACh-mediated increase of the magnitude of electromotility. Elevation of the intracellular calcium concentration apparently activates CAMKII which, in turn, phosphorylates membrane or cytoskeletal substrate(s). This molecular modification probably leads to reduced axial cell stiffness and subsequent increase of the electromotile response.

The effect of chronic otitis media on the immunoreactivity of human inner ear.

Twenty temporal bones (TBs) were removed from autopsy cases and prepared for immunohistochemical examination. Ten TBs were free of ear disease whereas the other ten TBs showed the signs of chronic otitis media. Expression of markers for monocyte-macrophages (25F9, 27E10) and natural killer cells (anti-Leu-11) was examined immunohistochemically. There were no specific positive stainings with 25F9 or anti-Leu-11 antibodies in any of the specimens. Staining for 27E10 was found to be negative in each section obtained from normal cochlea. However, 27E10 positivity was detected in three of ten TBs with signs of chronic ear inflammation. This positivity can be explained by two theories: (1) activated monocytes can enter the inner ear from the systemic circulation as a consequence of chronic antigen challenge; (2) mesothelial cells could become activated as a result of a cross-reaction, with resultant positivity. Development of sensorineural hearing loss in some cases of chronic otitis media may be due to these immunological reactions.

Impaired bronchomotor responses to field stimulation in guinea-pigs with cisplatin-induced neuropathy.

Pre-treatment with cisplatin (3 mg/kg) i.p. once a day over 6 days induced sensory neuropathy as confirmed by femoral nerve conduction velocity test and significantly decreased contractions induced by electrical field stimulation (100 stimuli, 20 V, 0.1 ms, 20 Hz) in isolated main bronchial rings from guinea-pigs. The field stimulation-induced non-adrenergic, non-cholinergic (NANC) relaxations, however, were amplified in rings from animals with cisplatin neuropathy. The NANC relaxation response was completely blocked by 30 microM N(G)-nitro-L-arginine methyl ester in preparations from both control and cisplatin-treated animals. Superoxide dismutase (40 units/ml) was without effect on NANC relaxation in control rings, however, it substantially decreased NANC relaxation in preparations from animals with cisplatin neuropathy. These results show that cisplatin-induced sensory neuropathy is accompanied by attenuation of neural bronchoconstriction and an enhanced NANC relaxation. The latter is in part attained by an increased peripheral superoxide production.

[Investigation of the cerebral projection of the vestibular system using positron emission tomography]. / A vestibularis ingerület központi idegrendszeri feldolgozásának agyaktivációs vizsgálata pozitronemissziós tomográfiával.

The authors investigated the cerebral projection of the vestibular system, using positron emission tomography, in right-handed subjects. Both sided cold caloric stimulation was used in every volunteer (n = 6). A detailed map of activated and deactivated brain regions is included. This portrays changes caused by vestibular stimulation. The contralaterally activated regions according to the stimulation side were: postcentral gyrus, transvers temporal gyrus, superior temporal gyrus, posterior part of the insula, claustrum, putamen, inferior parietal lobule, precentral gyrus, premotor cortex, cingulate gyrus. The ipsilaterally activated regions were: transvers temporal gyrus, superior temporal gyrus, inferior parietal lobule, posterior part of the insula. There was no hemispherial dominance. The activated regions partially correspond with previous results in the literature. It would like to be pointed out the Brodmann 6 region as the cortical manifestation of involuntary isometric tightening of muscles. The contralaterally deactivated regions were: inferior, superior and medius temporal gyrus, medial and medius frontal gyrus, inferior occipital gyrus, parahippocampal gyrus and hippocampus. Ipsilaterally deactivated regions were: superior and medial frontal gyrus, inferior temporal gyrus, angular gyrus, parahippocampal gyrus and hippocampus, fusiform and inferior occipital gyrus. There was prominent hemispherial dominance in the stimulated, ipsilateral side. The deactivation based functional connection between the hippocampus and the vestibular system was pointed out in such a relation for the first time in this report.

[Phoniatric studies in myasthenia gravis patients]. / Phoniatrische Untersuchungen an Patienten mit Myasthenia gravis.

The authors have for the first time evaluated the basic parameters of the voice using computed voice analysis in patients with myasthenia gravis (MG). The aim of the study was to introduce an objective method suitable for the assessment of dysphonic symptoms, which predominate in bulbar, oculobulbar and generalized MG. Voice profile studies included the evaluation of the singing voice range, voice dynamics, maximum phonation time, and mean fundamental frequency and intensity during speech. The characteristic of the stroboscopic picture was also determined. Investigations were carried out before and after the intake of Mestinon, a reversible cholinesterase inhibitor, and healthy subjects were used as a control group. In MG, the voice range and dynamics are badly impaired, maximum phonation time is shortened, the mean fundamental frequency during speech is increased, while the intensity is decreased. Mestinon resulted in an improvement in all these parameters, however, they were still impaired in comparison to the control subjects. Most changes were found to be statistically significant. The authors emphasize the role of the otolaryngologist and objective phoniatric methods in the evaluation of MG and other myasthenia-like neurological diseases. The use of these methods for the assessment of phoniatric symptoms in neurological diseases is highly recommended.