The responses of dorsal horn neurones to controlled mechanical stimulation of the hindlimb skin in the rabbit

The functional characteristics and spatial arrangement of Type I mechanosensitive units found in the sural nerve of the anaesthetized rabbit have been investigated.There are approximately 108 Type I units innervating a skin area of about 59.1 cm² supplied by the sural nerve giving an innervation density of 1.83. This innervation density of 1.83 does not vary over the skin territory innervated by the sural. The dome/fibre ratio was 2.7.The domes were found to be distributed in a dispersed but fairly regular pattern. The average nearest neighbour distance was 5.3 mm. A stimulus of 5.5 threshold units showed the existence of a small receptive field of radius 2 mm surrounding each dome; at a 3 mm radius even the largest 2 mm indentation failed to evoke a response.The response of the Type I units exhibited 4 distinct phases:

1. (1) a dynamic phase

2. (2) a transient adaptive phase

3. (3) a highly irregular static phase

4. (4) an off phase. The impulse frequency/static displacement relationship was best fitted by a power function. The impulse frequency/velocity characteristic became horizontal at an average value of 15 μm/ms. A power function provided the best fit for this relationship.

The possible physiological significance of the differences between properties of Type I receptor populations in the rabbit and cat are discussed.     

Distribution of gentamicin by immunofluorescence in the guinea pig inner ear

Summary We studied the distribution of gentamicin in the inner ear, brain and kidney of the guinea pig following intraperitoneal administration or perfusion of gentamicin through the perilymphatic space. The resulting histopathologcial changes were examined by immunofluorescence using antigentamicin antiserum. After perfusion of gentamicin through the perilymphatic space, specific fluorescence was found in the cochlea, and was especially prominent in the outer hair cells, basilar membrane and basilar crest. Although no fluorescence was observed in the cochlea following intraperitoneal administration of high doses of gentamicin, type I hair cells in the vestibule were seen to be selectively stained with the antibody. Furthermore, some of the vestibular ganglion cells, Purkinje cells and unidentified nuclei in the brain stem were also stained. In particular, fine granules showing relatively intense fluorescence were recognized in the cytoplasm of the stained cells. In the cortex of kidney, only proximal tubular cells were stained with intense fluorescence. Our results suggest that the aminoglycoside antibiotics have two sites of action: one is the cell membrane of the sensory hair cells and the other is the cytoplasm.This study was supported in part by a grant from the Ministry of Education, Science and Culture of Japan, and by a Research Grant for Specific Diseases from the Ministry of Health and Welfare to the Acute Profound Deafness Research Committee of Japan     

Effect of adenotonsillectomy on middle ear status in children

OBJECTIVE: To determine the effects of adenotonsillectomy as compared with watchful waiting on the middle ear status of children. STUDY DESIGN: Randomized controlled trial. METHODS: We recruited 300 children between 2 and 8 years of age who were selected for adenotonsillectomy according to current medical practice. Excluded from the trial were children with very frequent throat infections (more than 6 per year) or obstructive sleep apnea. Participants were randomly assigned to either adenotonsillectomy or watchful waiting. Main outcome measure was the percentage of children with unilateral or bilateral otitis media diagnosed at the scheduled follow-up visits according to an algorithm combining tympanometry and otoscopy. RESULTS: The percentages of children in the adenotonsillectomy and watchful waiting group diagnosed with otitis media at baseline and at 3, 6, 12, 18, and 24 months were 27.7 versus 30.5, 16.8 versus 25.2, 18.3 versus 21.2, 12.3 versus 15.2, 17.6 versus 15.5, and 14.7 versus 10.3%, respectively (P < .10). In the subgroup of children selected for adenotonsillectomy predominantly because of recurrent or persistent otitis media, hearing loss, or recurrent upper respiratory tract infections (n = 111) and in the subgroup of children diagnosed with otitis media at inclusion (n = 82), the occurrence of otitis media did not differ significantly between the adenotonsillectomy and watchful waiting group during the entire follow-up period. CONCLUSION: We conclude that in a large proportion of children selected for adenotonsillectomy according to current medical practice, including those with otitis media or related complaints, no beneficial effect of adenotonsillectomy on middle ear status is to be expected.     

Drug delivery to the cochlea using PLGA nanoparticles

OBJECTIVES: This study aimed to investigate the efficacy of encapsulating therapeutic molecules in poly lactic/glycolic acid (PLGA) nanoparticles for drug delivery to the cochlea. STUDY DESIGN: An experimental study. METHODS: We examined the distribution of rhodamine, a fluorescent dye, in the cochlea, liver, and kidney of guinea pigs. Intravenous injection of rhodamine or rhodamine-encapsulated PLGA nanoparticles was used to target the fluorescent dye systemically to the liver, kidney, and cochlea, and these molecules were applied locally to the round window membrane (RWM) of the cochlea. The localization of rhodamine fluorescence in each region was quantitatively analyzed. RESULTS: After systemic application of rhodamine nanoparticles, fluorescence was identified in the liver, kidney, and cochlea. The systemic application of nanoparticles had a significant effect on targeted and sustained delivery of rhodamine to the liver but not the kidney or cochlea. Rhodamine nanoparticles placed on the RWM were identified in the scala tympani as nanoparticles, indicating that the PLGA nanoparticles can permeate through the RWM. Furthermore, the local application of rhodamine nanoparticles to the RWM was more effective in targeted delivery to the cochlea than systemic application. CONCLUSIONS: These findings indicate that PLGA nanoparticles can be an useful drug carrier to the cochlea via local application.     

Novel strategy for treatment of inner ears using a biodegradable gel

OBJECTIVE: The present study aimed to evaluate the efficacy of a biodegradable hydrogel as a drug-delivery medium for the inner ear. Brain-derived neurotrophic factor (BDNF) was chosen as the agent to be administered. METHOD: First, we used an enzyme-linked immunosorbent assay to measure BDNF concentrations in the cochlear fluid after placing a hydrogel containing this agent onto the round-window membrane of the ear. Second, the functional and histologic protection of the auditory primary neurons (spiral ganglion neurons [SGNs]) by BDNF applied through the hydrogel was examined using an animal model of SGN degeneration. RESULTS: The results revealed sustained delivery of BDNF into the cochlear fluid by way of the hydrogel. Second, the functional and histologic protection of the auditory primary neurons (SGNs) by BDNF applied through the hydrogel was examined using an animal model of SGN degeneration. The measurement of electrically evoked auditory-brainstem responses demonstrated that BDNF delivered by way of the hydrogel significantly reduced the threshold elevation. Immunohistochemistry for neurofilament 200 kD demonstrated increased survival of SGNs because of BDNF application through the hydrogel. CONCLUSION: These findings indicate that biodegradable hydrogels can be used for drug delivery to the inner ear.     

In vivo demonstration of the absorptive function of the middle ear epithelium

The present study investigated in vivo fluid and ion transport across the middle ear epithelium. The tympanic membrane of rats was punctured under general anesthesia. A capillary tube was fitted to the external auditory canal and the bulla filled with various solutions. Middle ear (ME) fluid volume variations were then measured at constant pressure.

When saline was used, a linear decrease of fluid volume was apparent. Replacement of sodium with a non-permeable cation (N-methyl-d-glucamin) reduced the absorption rate from 0.065 ± 0.008 to 0.019 ± 0.003 μl/min (P < 0.05, n = 6). Similarly, amiloride (10⁻³ M), a sodium channel antagonist, reduced the absorption rate to 0.027 ± 0.006 μl/min (P < 0.05, n = 6). Net absorption was abolished when chloride was substituted with gluconate: −0.008 ± 0.004 μl/min (P < 0.02, n = 6), which might have been related (i) to the role of chloride as a diffusible anion through the paracellular pathway, or (ii) to the secretion of chloride through apical channels. However in this condition, 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid, a chloride channel blocker, did not affect the rate of fluid exchange −0.008 ± 0.007 μl/min (P = 0.75, n = 6).

This model provides the first in vivo evidence for the absorptive function of the ME. Fluid introduced into the ME cavity disappears due to active transport through the mucosa. This process is sodium-dependent and can be hindered by high concentration of amiloride. The rate of absorption is high enough to allow total clearance of fluid from the cavity of the middle ear within 13 h. This process might play a role in the maintaining a fluid-free and gas-filled middle ear cavity.     

Middle-ear ceruminous adenoma as a rare cause of hearing loss and vertigo: case reports

Middle-ear ceruminous adenomas are rare benign neoplasms arising from the epithelium of the middle ear. Progressive hearing loss, ear fullness and tinnitus are common symptoms of this tumour; facial nerve paresis and vestibular disturbances occur very infrequently. We present two cases of middle-ear ceruminous adenomas, one showed rapid unilateral hearing loss with aural fullness, followed by purulent aural discharge and vertigo. In the second case, the disease affected an already deaf ear and the only symptom of the disease was increasing vertigo. The clinical features, intraoperative findings, and histological and radiological findings are presented. The cases are compared to those described in the literature.     

Magnetic resonance imaging in neonatal encephalopathy

Magnetic resonance imaging may provide invaluable information in the term born neonate with encephalopathy. However, both hardware and sequences may need adaptation from normal adult protocols. Sedation is often required to obtain good quality imaging, but anaesthesia is not necessary in this population. The perinatal history may predict the pattern of brain lesions, which, in turn, may be used to predict the neurodevelopmental outcome. Image interpretation is not easy and requires a full clinical history in addition to experience of both normal and abnormal neonatal brain appearances. Lesions evolve rapidly, and perinatally acquired leasions are at the most obvious 1-2 weeks from delivery. Early imaging in the first few days from presentation should always include diffusion-weighted sequences to identify early ischaemic change. Advanced techniques such as venography, angiography and perfusion-weighted imaging may be useful in certain situations, and serial imaging may help differentiate perinatal-acquired lesions from other pathologies.     

Vanishing white matter disease in a child presenting with ataxia

Vanishing white matter disease is a recently described leukoencephalopathy that is characterized by chronic and episodic neurological deterioration. These episodes often follow periods of fever or minor head trauma. It frequently presents in childhood with problems of ataxia and tremor. Five genes have been identified for the disease, EIF2B1-5, which encode the five subunits of translation initiation factor eIF2B. Mutations in each of the genes may independently cause the disease. The defect in eIF2B results in abnormalities in translation and its regulation, leading to abnormalities in protein synthesis and its regulation. Magnetic resonance imaging of the brain reveals extensive cerebral white matter abnormalities with evidence of white matter rarefaction and cystic degeneration, which has been confirmed pathologically. We report the first confirmed Australasian patient.     

Contributors to white matter damage in the frontal lobe in Alzheimer's disease

Abnormalities of cerebral white matter are present in a majority of patients with Alzheimer's disease (AD) and probably contribute to motor dysfunction and cognitive impairment. The white matter abnormalities are usually attributed to degenerative vascular disease and cerebral amyloid angiopathy (CAA) but the evidence is scanty or inconclusive. In the present study we examined sections of frontal lobe from 125 autopsy-confirmed cases of AD and assessed the relationship of degenerative large and small vessel disease, CAA, parenchymal Abeta load and APOE genotype, to several objective measures of white matter damage: extent of immunolabelling for glial fibrillary acidic protein (GFAP), axonal accumulation of amyloid precursor protein (APP), axon density in superficial and deep white matter, and intensity of staining for myelin. We found no association between atherosclerosis, arteriolosclerosis, CAA or APOE genotype and white matter damage. However, labelling of white matter for GFAP correlated strongly with the parenchymal Abeta load (P = 0.0003) and with APP accumulation (P = 0.008). Our findings suggest that severity of frontal white matter damage in AD is closely related to parenchymal Abeta load and that in most cases the contribution of degenerative vascular disease, CAA and APOE is relatively minor.