Joaquín Poch-Broto

Trimetazidine prevents cochlear lesions induced by intraperitoneal and perilymphatic administration of kainic acid.

The protective activity of trimetazidine (TMZ) against cochlear neurotoxicity induced by intraperitoneal and intracochlear administration of kainic acid (KA) has been analyzed. The amplitude of the CAP N1 wave was significantly higher in KA rats pretreated with TMZ, independently of the administration route, than in those only treated with KA. However, CAP N1 amplitude of both TMZ pretreated and non-pretreated animals was always lesser than the N1 wave amplitude observed in the control group. The CAP N1 latency did not show any significant difference between KA and TMZ+KA groups except at high intensities of 8 and 12 kHz. As a complementary control, we have demonstrated that the intraperitoneal administration of TMZ (5 mg/kg) alone did not affect either the electrophysiological activity or the morphology of the auditory nerve. Morphological results fit well with electrophysiology. Some isolated swollen afferent fibers were observed in TMZ+KA cochleae, the swollen dendrites being sparser than in the KA only treated animals. In TMZ+KA animals, the cochlear apical coils were less affected than the basal coils. Our results are in agreement with recent clinical studies and suggest that TMZ could be an active drug on cochlear impairment linked to hypoxic-ischaemic syndromes.

Cochlear microphonic potentials: a new recording technique.

A new instrumentation and a particular method for detecting and recording cochlear microphonic potentials (CMPs) are described here. The CMPs were recorded in rats by means of pure tones (4,000, 2,000, 1,000, 500, and 250 Hz) and intraepidermic electrodes; the electrocochleography technique was avoided. An experimental design that included the use of a glutamatergic agonist (kainic acid [KA]) and an aminoglycoside antibiotic (kanamycin [KANA]) was carried out to demonstrate the origin of the recorded potential. Morphological studies showed that KA selectively eliminated the afferent type I dendrites of the spiral ganglion, while the administration of KANA resulted in the absence of outer hair cells. When CMPs were recorded after KA administration, no alterations were detected. In contrast, KANA administration resulted in the absence of any selective electrophysiological activity corresponding to CMPs. All these results were compared with the recording of the compound action potential of the eighth nerve obtained by electrocochleography. These findings and the great specificity of the reproduction of the sound stimulus confirm that the CMPs can be recorded by the new equipment.

Parapharyngeal space tumors: Fifty-one cases managed in a single tertiary care center

Abstract Conclusions: Pre-operative planning for parapharyngeal tumors must include meticulous analysis. Factors such as tumor size, distance to cranial base, and relation to neurovascular structures must guide the selection of a surgical approach. Objective: To summarize experience in diagnosis and surgical management of parapharyngeal tumors, analyzing the frequencies of various tumoral types, clinical presentation, choice of surgical approach and outcomes. This study also compares the results with the most relevant case series in the literature. Methods: A retrospective review was performed of the records of 51 patients treated by the team, from 1984–2012. Only primary tumors were included, excluding invasion from adjacent spaces and metastatic disease. All patients underwent imaging studies and surgical resection of the neoplasm. Cytological analysis and arteriography were used on an individualized basis. Surgical excision was performed via different approaches, predominantly through a cervicoparotid route. Results: Benign neoplasms were predominant (80%), and the most frequent tumor was pleomorphic adenoma. FNAC had a 100% accuracy to differentiate benign vs malignant tumors. The most common post-operative sequel was compromise of a cranial nerve, and three patients presented local complications after surgery. After follow-up, only three of 41 patients with benign tumors had recurring disease.

Cochlear microphonic audiometry: a new hearing test for objective diagnosis of deafness

Conclusions. Objective audiometric tests could constitute a valuable tool for detection of deafness. This could be especially useful in children (universal newborn hearing screening) and non-collaborative patients, who are especially difficult candidates for classic audiometry. The cochlear microphonic audiometry (CMA) technique offers the possibility of obtaining objective audiometric profiles, highly correlated with those obtained by pure tone audiometry (PTA). Therefore, CMA could be used as an alternative test to obtain the audiometric profile of these patients. Objective. The main purpose of the present study was to demonstrate that CMA provides objective audiometric profiles by avoiding active participation by the patient. Subjects and methods. CMA specific equipment, improved for non-invasive recording of cochlear microphonic potentials, was used. This tool plots the recordings obtained as the classic audiogram. Verification of the method was carried out in adult patients by comparing the PTA with the CMA audiometric profiles obtained for each patient. Results. Our findings showed that audiometric profiles obtained from CMA are highly correlated, without statistical differences, to those obtained with PTA. More than 81% of patients explored (91.67% at 250 Hz) exhibited differences below 10 dB(HL) between tests at all exploration frequencies, while a low number of cases showed differences over 20 dB(HL).

Cellular and molecular bases of neuroplasticity: brainstem effects after cochlear damage

After a cochlear lesion or auditory nerve damage, afferent connections from auditory ganglia can be highly altered. This results in a clear reduction of auditory input and an alteration of connectivity of terminals on cochlear nuclei neurons. Such a process could stimulate the reorganization of the neural circuits and neuroplasticity. Cochlea removal has been demonstrated to be a good model in which to analyse brainstem neuroplasticity, particularly with regard to the cochlear nuclei. After cochlea removal three main periods of degeneration and regeneration were observed. Early effects, during the first week post lesion, involved acute degeneration with nerve ending oedema and degeneration. During the second and, probably, the third post lesion weeks, degeneration was still present, even though a limited and diffuse expression of GAP-43 started. Around 1 month post lesion, degeneration at the cochlear nuclei progressively disappeared and a relevant GAP-43 expression was found. We conclude that neuroplasticity leads neurons to modify their activity and/or their synaptic tree as a consequence of animal adaptation to learning and memory. For the human being neuroplasticity is involved in language learning and comprehension, particularly the acquisition of a second language. Neuroplasticity is important for therapeutic strategies, such as hearing aids and cochlear implants.

Effects of aging on C57BL/6J mice: an electrophysiological and morphological study.

Presbycusis is a progressive hearing loss associated with aging that manifests as deafness linked to cochlear morphological degeneration. The effects of aging on the auditory system were studied in C57BL/6J mice using electrophysiological (brainstem auditory evoked potentials; BAEP) and morphological techniques. Cochleae of animals aged 1, 6, 9, 12, 15, 18, 21, or 24 months old were used for that purpose. The BAEP showed a progressive increase in latency and a reduction in amplitude. Morphological studies demonstrated total degeneration of the organ of Corti, which was replaced by a single epithelial layer. An affinity histochemistry study demonstrated minor modifications of glycoconjugates in the organ of Corti during the aging process.

The impact of comorbidity on the survival of patients with laryngeal squamous cell carcinoma

Abstract Conclusions: In survival analysis, the combined Charlson comorbidity index (CCI) can be considered as a prognostic factor independent of the tumor node metastasis (TNM) classification, tumor stage, and tumor location. Severe comorbidity was the factor that had the greatest impact on prognosis in cases of initial tumor. Objective: To study the influence of comorbidity on the survival of patients undergoing surgery for larynx cancer. Methods: This was a retrospective study of the survival of 231 patients with laryngeal cancer who underwent surgery between 1995 and 2002. The CCI was used to assess comorbidity, the Kaplan–Meier method was used for survival analysis, and the Cox proportional risk regression model was used to identify independent prognostic factors. Results: The multivariate analysis of specific mortality showed that patients classified as having severe comorbidity (CCI) were more likely to die (adjusted hazard ratio (adjHR) 1.85, 95% confidence interval (CI) 1.07–3.17). This difference was more important in patients with early tumor stages than in those with advanced stages.

In vitro long-term development of cultured inner ear stem cells of newborn rat

The adult mammalian auditory receptor lacks any ability to repair and/or regenerate after injury. However, the late developing cochlea still contains some stem-cell-like elements that might be used to regenerate damaged neurons and/or cells of the organ of Corti. Before their use in any application, stem cell numbers need to be amplified because they are usually rare in late developing and adult tissues. The numerous re-explant cultures required for the progressive amplification process can result in a spontaneous differentiation process. This aspect has been implicated in the tumorigenicity of stem cells when transplanted into a tissue. The aim of this study has been to determine whether cochlear stem cells can proliferate and differentiate spontaneously in long-term cultures without the addition of any factor that might influence these processes. Cochlear stem cells, which express nestin protein, were cultured in monolayers and fed with DMEM containing 5% FBS. They quickly organized themselves into typical spheres exhibiting a high proliferation rate, self-renewal property, and differentiation ability. Secondary cultures of these stem cell spheres spontaneously differentiated into neuroectodermal-like cells. The expression of nestin, glial-fibrillary-acidic protein, vimentin, and neurofilaments was evaluated to identify early differentiation. Nestin expression appeared in primary and secondary cultures. Other markers were also identified in differentiating cells. Further research might demonstrate the spontaneous differentiation of cochlear stem cells and their teratogenic probability when they are used for transplantation.

Pharyngo-cutaneous fistula: an old problem revisited.

Abstract Conclusion: Pharyngo-cutaneous fistula is the most common complication after total laryngectomy (TL), with many factors linked to its emergence. However, it has rarely been associated with the type of pharyngeal suture. We conclude that the technique of surgical closure of the pharynx and care in the tightness of the suture seem to be fundamental factors for pharyngo-cutaneous fistula development. Objective: The aim of present work was to determine whether the type of pharyngeal suture can be considered as a major risk factor for developing a pharyngo-cutaneous fistula following TL. Methods: We carried out a series of 157 consecutive TLs. In the first 90 procedures, we performed a pharyngeal closure technique with T-shaped interrupted stitches reinforced with constrictors. In the other 67 cases, a doubled continuous suture technique with reinforcement with the cutaneous flap was developed. Results: In all, 25.5% of the cases sutured with the interrupted stitches developed a fistula while only 2.9% of the patients that underwent continuous suture developed a fistula.

Cochlear nuclei neuroplasticity after auditory nerve and cochlea removal

Hearing loss clearly alters the function and connectivity in auditory pathways in the brain. The effects of an auditory receptor lesion on the auditory pathway might be linked to the absence of peripheral stimulation on the first level of the auditory pathway (cochlear nuclei, CN). Loss of stimulation affects the pathway connectivity, at least in the CN, inducing the reorganization of the neural circuits. This reorganization may reduce the efficiency of some deafness therapies, including cochlear implants. Cochlea removal has been shown to be a good model for analysing neuroplasticity in the CN. Three main periods of degeneration and regeneration were found after cochlea removal. During the first week after cochlea removal, early effects included auditory nerve fibre degeneration, and the progressive degeneration of nerve endings on CN neurons. Some CN neurons degenerate. From the second week after cochlea removal a very limited and diffuse expression of GAP-43, a protein linked to developing or regenerating axon growth cones, was found. Expression was observed in small nerve endings connecting cochlear nuclei neurons. One month after cochlea removal, CN were stabilized with a clear reduction of new neuron degeneration. At this time a very relevant expression of GAP-43 was found around remaining neurons, in particular in the ventral cochlear nuclei. Molecular aspects and control of neuroplasticity in cochlear nuclei still remains controversial, even though it is clear that trophic factors and many other substances (i.e. neurotransmitters) have been involved in neuroplasticity.