RESUMO
Acoustically evoked neural activity has been recorded from the brainstem and auditory cortex of guinea pigs after complete destruction of the organ of Corti by the aminoglycosidic antibiotic amikacin. These responses to sound differ in important respects from the evoked potentials normally recorded from the auditory pathways. At the brainstem level they resemble the potentials reported by others after stimulation of the vestibular nerve.
Assuntos
Córtex Auditivo/fisiologia , Tronco Encefálico/fisiologia , Potenciais Evocados Auditivos , Órgão Espiral/fisiologia , Estimulação Acústica , Amicacina/farmacologia , Animais , Cóclea/fisiologia , Eletrodos Implantados , Cobaias , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/fisiologia , Órgão Espiral/efeitos dos fármacos , Janela da Cóclea/efeitos dos fármacos , Núcleos Vestibulares/fisiologia , Vestíbulo do Labirinto/fisiologiaRESUMO
Scanning electron microscopy was employed to investigate hair cell morphology at different stages in the development of experimentally induced hydrops in the guinea pig. A particular form of morpho-pathology, never before described, was identified as characteristic of hydropic cochleas. The pathology was characteristically identified as atrophy of the short and middle stereocilia on the outer hair cells while the inner hair cell stereocilia did not have such a pathology. The atrophy was restricted to the upper cochlear turns in remarkable correspondence with the low/middle frequency sensitivity loss and was detected only at the end of the period of fluctuating thresholds. These stereocilia perturbations appear therefore to be linked with the threshold fluctuations and represent the first evidence for a clear correlation between hair cell morphology and physiology in the experimental model of endolymphatic hydrops. Such a morphopathology might also be expected to occur in cochleas of Menière's patients but may have been overlooked in the past because of the discrete nature of the pathology.
Assuntos
Cóclea/ultraestrutura , Edema/patologia , Células Ciliadas Auditivas/ultraestrutura , Doenças do Labirinto/patologia , Animais , Atrofia/patologia , Modelos Animais de Doenças , Endolinfa , CobaiasRESUMO
This paper reports on a dynamic study of the morphological changes within the cochlear and vestibular ganglia of the guinea pig after local application of Sisomicin in the inner ear. The treatment leads to a rapid, complete and irreversible destruction of the sensory cells in the cochlear and vestibular neuroepithelia. A progressive degeneration of the type I and type II afferent neurons, presenting a decreasing gradient from the base towards the apex of the cochlea, is rapidly observed and becomes almost complete as early as 15 days after the peripheral injury. Five months after the treatment the spiral ganglion cells have almost completely disappeared. At this time the vestibular ganglion cell density appears normal but the neurons exhibit important signs of alteration. Such damage to the cochlear and vestibular afferent neurons may result from either retrograde neuronal degeneration and/or direct neurotoxic effect of the drug. Thus the combination of the two mechanisms could lead to neuronal losses in spiral and Scarpa's ganglia after the local aminoglycoside intoxication of the inner ear. The difference in the time course of degeneration for these two afferent ganglia could be due to their specific susceptibilities or to their different anatomical locations.
Assuntos
Degeneração Neural/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Sisomicina/toxicidade , Gânglio Espiral da Cóclea/efeitos dos fármacos , Nervo Vestibular/efeitos dos fármacos , Animais , Cobaias , Microscopia Eletrônica de Varredura , Neurônios Aferentes/citologia , Neurônios Aferentes/ultraestrutura , Gânglio Espiral da Cóclea/citologia , Gânglio Espiral da Cóclea/ultraestrutura , Nervo Vestibular/citologia , Nervo Vestibular/ultraestruturaRESUMO
In our companion paper (Le Calvez et al., 1998), the levels of distortion product otoacoustic emissions (DPOAE) were collected in the ears of CD1 mice with progressive degeneration of cochlear outer hair cells (OHC). Their comparison to standard functional measurements such as auditory-evoked brainstem responses (ABR) showed that CD1 ears could be classified as normal or impaired in a frequency-specific manner using DPOAE levels. The present work reports how DPOAE phases and levels of young CD1 mice were affected by varying the frequency ratio of eliciting stimuli at frequencies f1 and f2. Normally hearing CBA/J mice served as controls. The rate of phase change of DPOAE when f1 was varied and f2 was fixed allowed the group delay of DPOAE to be derived. The changes of DPOAE levels during this procedure disclosed bandpass characteristics that several reports (Fahey and Allen, 1986; Brown and Gaskill, 1990) assumed to be the reflection of important features of cochlear micromechanics, possibly in relation to the coupling of OHCs to the tectorial membrane. Group delays became significantly shorter when ABR thresholds exceeded 40 dB elevation. The bandpass filter characteristics strikingly depended on auditory function so that the optimal ratio f2/f1 progressively shifted from 1.24 to 1.50 or more when hearing loss increased. A difference was also noted between CD1 ears whose ABR thresholds were not yet increased and control CBA/J (optimal ratio 1.20). Scanning electron microscopy disclosed a variety of often minor OHC lesions that were only roughly correlated with cochlear function. However, the presence of abnormalities in the reticular lamina associated with early changes of DPOAE fine structure as a function of f2/f1 supported the hypothesis of some involvement of micromechanical features in the bandpass filter characteristics of DPOAE. The sensitivity of their measurement in pathological situations is potentially interesting.
Assuntos
Potenciais Microfônicos da Cóclea/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Células Ciliadas Auditivas Externas/patologia , Perda Auditiva Neurossensorial/fisiopatologia , Órgão Espiral/patologia , Emissões Otoacústicas Espontâneas/fisiologia , Animais , Limiar Auditivo/fisiologia , Células Ciliadas Auditivas Externas/ultraestrutura , Perda Auditiva Neurossensorial/genética , Camundongos , Camundongos Endogâmicos CBA , Camundongos Mutantes , Órgão Espiral/ultraestruturaRESUMO
Several studies have reported variations in shape and size of stereociliary bundles and in a limited number of observations have associated them to type I and type II hair cells. A systematic study has been undertaken for which a technique was developed in order to identify both cell types and their corresponding hair bundles. Numerous fissures were obtained in saccular epithelia and observed in scanning electron microscopy. Saccular type I and type II hair cells in the guinea pig were found to have distinctive hair bundles. The tallest stereocilia of almost all type I cells were longer than 6 microns, and were shorter in the striola compared to the periphery. In contrast, the tallest stereocilia of almost all type II cells were shorter than 6 microns and were not found to vary notably in size from the striola to the periphery. Hair bundles with stereocilia organized in straight or in staggered rows were found for both types of cells across the whole saccular epithelium, with no apparent particular distribution. Possible physiological significance of differences in hair bundles is discussed.
Assuntos
Células Ciliadas Auditivas/ultraestrutura , Sáculo e Utrículo/ultraestrutura , Animais , Cílios/ultraestrutura , Epitélio/ultraestrutura , Cobaias , Células Ciliadas Auditivas/citologia , Microscopia Eletrônica de Varredura , Sáculo e Utrículo/citologiaRESUMO
In guinea pigs that had been treated with very large doses of the aminoglycoside amikacin (14 x 450 mg/kg/day, i.m.) clear, short-latency responses to various click stimuli could be recorded at the round window. When the same cochleas were examined histologically, no outer or inner hair cells could be found along the entire length of the basilar membrane, save for a very few outer hair cells remaining at the apex. The response patterns resembled that of the compound action potential, and various characteristics suggest that they were of neural origin. Vestibular function, investigated by electronystagmography during rotation, appeared normal, as did most of the saccular and utricular hair cells. Transmission electron microscopy revealed a significant number of cochlear nerve fibres still innervating the remnants of Corti's organ. In other cochleas with similarly extensive destruction induced by another aminoglycoside (sisomycin, 14 x 125 mg/kg/day, 15 days as well as 3 months post-Rx), no responses could be recorded from the round window. Cochleas that were less affected, with the upper turns preserved, gave only small, long-latency responses. These preliminary observations are confirmed by further experiments now in progress. They suggest that unless a considerable number of inner hair cells remained undetected in the lower basal turn, a possibility that appears highly unlikely, there was either a direct mechanical excitation of cochlear nerve fibres, or an acoustical stimulation of vestibular sense organs.
Assuntos
Amicacina/toxicidade , Cóclea/efeitos dos fármacos , Canamicina/análogos & derivados , Estimulação Acústica , Amicacina/administração & dosagem , Animais , Membrana Basilar/efeitos dos fármacos , Membrana Basilar/patologia , Cóclea/patologia , Cóclea/fisiopatologia , Nervo Coclear/efeitos dos fármacos , Nervo Coclear/patologia , Nervo Coclear/fisiopatologia , Eletronistagmografia , Potenciais Evocados/efeitos dos fármacos , Cobaias , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/patologia , Doenças do Labirinto/induzido quimicamente , Doenças do Labirinto/patologia , Doenças do Labirinto/fisiopatologia , Sáculo e Utrículo/efeitos dos fármacos , Sáculo e Utrículo/patologia , Sisomicina/toxicidade , Vestíbulo do Labirinto/efeitos dos fármacos , Vestíbulo do Labirinto/fisiopatologiaRESUMO
Morphological changes of the eighth nerve were observed in the guinea pig between 1 month and 1 year after treatment with large doses of the antibiotic amikacin which resulted in complete cochlear hair cell destruction. The neural retrograde degeneration was found to be relatively fast, with a considerable loss (30 to 55%) of ganglion cells one month after treatment, continuously increasing (up to 85) after one year. Gross changes in the habenula perforata and in the spiral ganglion are described, together with ultrastructural alterations of organelles important for the cell metabolism and axonal transport. The rapid degeneration and the morphological findings suggest a direct influence of toxic substances on the ganglion cells.
Assuntos
Amicacina/efeitos adversos , Cóclea/efeitos dos fármacos , Canamicina/análogos & derivados , Gânglio Espiral da Cóclea/efeitos dos fármacos , Animais , Transporte Axonal/efeitos dos fármacos , Contagem de Células , Cobaias , Degeneração Neural , Órgão Espiral/efeitos dos fármacos , Gânglio Espiral da Cóclea/patologia , Gânglio Espiral da Cóclea/ultraestruturaRESUMO
Regional selectivity of gentamicin (GM) ototoxicity was studied in guinea pigs (GPs) using electrophysiological, morphological, autoradiographic and immunohistological observations following combined treatment with GM (150 mg/kg i.m.) and ethacrynic acid (EA) (30 mg/kg i.c. or i.v., 1.5 h after GM injection). The GPs were either continuously stimulated every 5 min with a series of 256 clicks (70 dB peSPL, 10/s) during 3 h for monitoring fast changes in VIII nerve compound action potential (CAP) after the EA injection, and thereafter kept in the animal quarters (background noise of 60 dB SPL) (group I), or similarly monitored for only 10 min after the EA injection and thereafter kept in a soundproof room (around 0 dB SPL) (group II). Whenever GM labelling was observed it was localized only in the sensory hair cells. From 3 h after EA injection, the GPs in group I presented threshold elevations in the high-frequency region, which progressed to 60-80 dB at all frequencies at and after 48 h. Parallel to the threshold pattern, GM uptake in outer hair cells (OHCs) was seen with an increasing concentration from apex toward base from 3 to 24 h, while after 48 h almost all OHCs were destroyed and inner hair cells (IHCs) were marked by GM. In group II no changes in CAP thresholds were observed until more than 24 h, although GM was detected in the hair cells from 6 h on. At this early stage, the distribution of GM lacked a clear pattern, particularly without a clear apex-base gradient, and GM deposits were found only around the basal body. However in both groups, in late stage (greater than 24 h), the base-apex gradient was more pronounced and GM was found throughout the cell body, with a marked concentration below the cuticular plate. These results suggest that GM may penetrate hair cells around the basal body and that activating the cells by sound potentiates both GM uptake and its intracellular toxicity.
Assuntos
Cóclea/efeitos dos fármacos , Ácido Etacrínico/toxicidade , Gentamicinas/toxicidade , Nervo Vestibulococlear/efeitos dos fármacos , Estimulação Acústica , Potenciais de Ação/efeitos dos fármacos , Animais , Autorradiografia , Cóclea/fisiopatologia , Interações Medicamentosas , Ácido Etacrínico/farmacocinética , Gentamicinas/farmacocinética , Cobaias , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/ultraestrutura , Células Ciliadas Auditivas Internas/efeitos dos fármacos , Células Ciliadas Auditivas Internas/ultraestrutura , Imuno-Histoquímica , Microscopia Eletrônica de Varredura , Monitorização Fisiológica , Nervo Vestibulococlear/fisiopatologiaRESUMO
After complete destruction of cochlear but preservation of vestibular hair cells in the guinea pig acoustically evoked responses can still be recorded from the round window up to the auditory cortex. At all levels these responses differ from those observed in normal animals but their frequency sensitivity and selectivity make them akin to responses from auditory organs. In a series of experiments a complete cochlear destruction was combined with a total or partial destruction of the vestibule. After complete cochlear and vestibular hair cell destruction no acoustic response could be recorded. But in cases of total cochlear and drastic ampullar and utricular destruction together with an almost undamaged saccular sensory epithelium the same peculiar acoustic responses could be observed. These results support the hypothesis of a functional acoustic reception by the saccule in a mammal.
Assuntos
Audição , Sáculo e Utrículo/fisiologia , Vestíbulo do Labirinto/fisiologia , Aminoglicosídeos/farmacologia , Animais , Antibacterianos/farmacologia , Cóclea/efeitos dos fármacos , Cóclea/fisiologia , Potenciais Evocados Auditivos , Cobaias , Células Ciliadas Auditivas/ultraestrutura , Nistagmo Fisiológico , Rotação , Sáculo e Utrículo/ultraestrutura , Vestíbulo do Labirinto/efeitos dos fármacos , Vestíbulo do Labirinto/ultraestruturaRESUMO
A series of acoustically evoked potentials can be recorded from the cochlea up to the auditory cortex in guinea pigs where the organ of Corti has been totally destroyed after extensive treatment with amikacin, but where some of the spiral ganglion neurons always remain and where the vestibular receptors are only slightly affected. The cochlear responses have been monitored in guinea pigs permanently implanted with a round window electrode and receiving such treatment. The normal auditory nerve compound action potential disappears within a few days, while the very typical response (diphasic, short latency (0.3 ms) small amplitude) appears. This response then remains remarkably constant in time as far as we could observe (up to almost one year). This response might be a component of the normal response, undiscernible under normal conditions but revealed by the selective impairment of the labyrinth by amikacin, in contrast to the global effect of every other known otodestructive agent. Some basic questions still remain: which fibres are effectively stimulated (cochlear or vestibular), what are their central projections, and what kind of sensation is conceivably associated with these responses?
Assuntos
Amicacina/toxicidade , Cóclea/fisiopatologia , Potenciais Evocados Auditivos , Canamicina/análogos & derivados , Órgão Espiral/efeitos dos fármacos , Animais , Córtex Auditivo/fisiopatologia , Limiar Auditivo , Cóclea/efeitos dos fármacos , Cóclea/patologia , Eletrodos , Potenciais Evocados Auditivos/efeitos dos fármacos , Cobaias , Monitorização Fisiológica , Degeneração Neural , Gânglio Espiral da Cóclea/fisiopatologia , Fatores de Tempo , Nervo Vestibulococlear/fisiopatologiaRESUMO
In a five and a half year-old child, a voluminous mandibular cyst was discovered by a dental check-up. The originality of this case consisted in the great volume of this asymptomatic lesion and the anterior localization in the mandible. Treatment was surgical, conserving the deciduous teeth and the underlying germs. The histopathological examination of the lesion confirmed the clinical and radiological aspects of follicular cyst. A regular clinical and radiologic surveillance was necessary until bone regeneration was complete, the risk of per and post-operative fracture being major.
Assuntos
Cistos/diagnóstico , Doenças Mandibulares/diagnóstico , Pré-Escolar , Cistos/patologia , Cistos/cirurgia , Assistência Odontológica para Crianças , Feminino , Humanos , Doenças Mandibulares/patologia , Doenças Mandibulares/cirurgia , Fraturas Mandibulares/etiologia , Complicações Pós-Operatórias , Fatores de Risco , Tomografia Computadorizada por Raios XRESUMO
We report here a case of sarcoidosis, observed in a 12 year-old algerian girl. When the child was examined, at an advanced stage of the disease, her clinical condition was very critical, associating blindness, cachexia, hepatic and splenic enlargement, and major hypercalcaemia. Though chest roentgenograms were normal, the results of both functional pulmonary tests and broncho-alveolar lavage were pathologic. The diagnosis of sarcoidosis was confirmed by the finding of an elevated level of Angiotensin-converting enzyme, and by histologic lesions observed in liver, kidney and conjunctiva biopsies. The corticosteroid treatment improved the general condition, but it failed to better the visual state.
Assuntos
Cegueira/etiologia , Hipercalcemia/etiologia , Sarcoidose/diagnóstico , Brônquios/patologia , Caquexia/etiologia , Criança , Túnica Conjuntiva/patologia , Oftalmopatias/diagnóstico , Feminino , Hepatomegalia/etiologia , Humanos , Rim/patologia , Fígado/patologia , Peptidil Dipeptidase A/sangue , Sarcoidose/terapia , Uveíte/etiologia , Uveíte Anterior/etiologiaRESUMO
Primary ovarian failure was observed in 2 sisters aged 17 and 4 years respectively presenting with congenital galactosaemia. The diagnosis of ovarian failure, clinically suggested in the older girl by the absence of puberty, was confirmed in both cases by a massive increase of baseline and post-stimulation plasma gonadotrophins. The elder sister had extremely low plasma oestradiol levels, and her ovaries were reduced to two strips of fibrous stroma almost devoid of follicles. In both cases the other endocrine glands seemed to be normal. Since the younger girl had received a galactose-free diet from birth, exogenous galactose toxicity could be ruled out. It appears from an analysis of the other 5 published reports that a metabolite of endogenous galactose is responsible for the ovarian lesions. The toxic effects of this metabolite may begin during intra-uterine life or after-birth.
Assuntos
Galactosemias/congênito , Doenças Ovarianas/etiologia , Adolescente , Pré-Escolar , Feminino , Galactose/metabolismo , Galactose/fisiologia , Galactosemias/complicações , Humanos , Hipogonadismo/etiologia , Doenças Ovarianas/fisiopatologiaRESUMO
Using the guinea pig middle ear model, we assessed decalcified, lyophylized, sterile heterotopic porcine ossicular xeno-implants based on a histology (optic and electron scan microscope) and immunologic (immunofluorscence) methods. Implants were placed in the middle ear and others in the dorsal subcutaneous area. Allo-implants were compared as controls. Implants were placed in the middle ear in 54 animals and skin implants in 14. Under the influence of BMP, the implant ossified in all cases in the middle ear. Intense immune recruitment was not observed. Inversely, there was a mononuclear infiltration reaction to the skin implants with formation of a fibrous capsule, immunoglobulin and complement influx and consequently sequestration. The allo-implants were partially reossified. These findings confirm the value of decalcification with hydrochloric acid for BMP induction, independent of species and the failure of attempted immune despecification. Implant outcome is not dependent on its antigen load, which is high compared with its weight, but on the site of implantation. The middle ear appears to be a privileged site of implantation.
Assuntos
Bioprótese , Osseointegração , Prótese Ossicular , Animais , Técnica de Descalcificação , Orelha Média , Liofilização , Cobaias , Projetos de Pesquisa , Esterilização , Transplante HeterotópicoRESUMO
Recent studies, and notably 24 hour polygraphic recordings, have provided accurate data on the qualitative and quantitative changes in the organization of sleep and wake periods which occur during childhood and adolescence. These studies explain the lack of adaptation of some subjects, notably young children and teenagers, to school hours. It is hoped that this knowledge of changes in circadian rhythms will be taken into account by those who decide on working hours in schools.