PubMed Health⌕ Search

Biomedical subjects

David Lobo

Publications and source records attributed to David Lobo.

7 recordsLinked to original sources

TNFalpha blockers do not improve the hearing recovery obtained with glucocorticoid therapy in an autoimmune experimental labyrinthitis.

The effectiveness of etanercept [tumour necrosis factor-alpha (TNFalpha) blocker] and corticoids in treating immuno-mediated inner ear disease (IMIED) was compared in an animal model of autoimmune labyrinthitis. IMIED is one of the few forms of sensorineural hearing loss that is reversible with proper medical treatment. While the effectiveness and usefulness of immunomodulating agents (corticosteroids) in treating IMIED have been demonstrated, TNFalpha antagonists, which inhibit granuloma formation in rheumatoid arthritis and other autoimmune diseases, have been considered as an alternative therapy. The efficacy of etanercept (anti-TNFalpha) was evaluated in a guinea pig model of experimental autoimmune labyrinthitis in which 25 guinea pigs were divided in a control group, which was used to document the rise in hearing thresholds following immunisation, and two experimental groups, which were treated with steroids (6-methylprednisolone) and anti-TNFalpha (etanercept), respectively, after the immunisation. Comparison of the auditory thresholds obtained by means of auditory brainstem response (ABR) revealed that the auditory thresholds of the two experimental groups were not statistically different (6-methylprednisolone: 41.5 dB, SD: 8.51; etanercept: 37.5 dB, SD: 7.91) and that both compared favourably with that of the control group (60 dB, SD: 7.91) at p=0.001. We therefore conclude that etanercept is as effective as glucocorticoids in an animal model of autoimmune labyrinthitis; however, the potential adverse effects and high price of the former advise against its use as an initial therapy for IMIED.

Analysis of Variance↗

Anti-adhesive properties of polytetrafluoroethylene (Gore-Tex) in middle ear surgery. An experimental study.

CONCLUSIONS: Polytetrafluoroethylene (PTFE) may represent a material that prevents adhesions when implanted in the middle ear. This characteristic can be used to improve the design of prostheses. OBJECTIVE: Prostheses in the middle ear have a relatively high failure rate due to extrusion, deformation and adhesion. Adhesion of prostheses to the walls of the tympanic cavity is the commonest cause of long-term hearing loss. The anti-adhesive properties of PTFE have been previously studied in abdominal and vascular surgery. To the best of our knowledge, this is the first work in which the properties of PTFE have been studied in the context of middle ear pathology. MATERIAL AND METHODS: In order to induce otitis media with effusion, 27 Wistar rats underwent a technique based on permanent cauterization of the pharyngeal Eustachian tube. PTFE was subsequently implanted in the middle ear. Rats that underwent cauterization without implantation and cauterization with implantation of hydroxyapatite and Plastipore were included as controls. RESULTS: Histopathological study of the tympanic bullae at 15 and 90 days after implantation demonstrated good biocompatibility of the PTFE implant under the analyzed conditions, with formation of a capsule around the material and no adhesions between the ear tissues and the prosthesis.

Acoustic Impedance Tests↗

Immunologic work-up study for inner ear disorders: looking for a rational strategy.

CONCLUSIONS: For the evaluation of a patient with suspected immune-mediated inner ear disease (IMIED), an exhaustive immunologic work-up study is not recommended if financial resources are limited. Analysis of antinuclear antibodies (ANA) and the immunophenotype of peripheral blood lymphocytes (PBL) proved to be the most useful tests in our population to support the clinical diagnosis of IMIED. OBJECTIVE: Owing to the lack of specific serological markers for the diagnosis of IMIED, an exhaustive immunologic work-up study for patients with suspected IMIED is usually performed. The aim of this study was to estimate the use of resources and the costs involved in the routine laboratory tests used for the diagnosis of IMIED. MATERIAL AND METHODS: This was a comparative study of two groups of patients with a high suspicion of diverse clinical forms of IMIED who were subjected to different serologic test designs. The cost of the classical immunologic work-up study used for the diagnosis of IMIED (n=125) was estimated in comparison with that of a more restricted examination, based on a recently reported high-risk profile, involving the analysis of ANA and PBL (n=57). RESULTS: The diagnostic efficiency of the two protocols was similar. The cost of a complete immunologic work-up study was 241.77 euros and that of the limited analysis was 53.12 euros.

Adolescent↗

Controversies and criticisms on designs for experimental autoimmune labyrinthitis.

Although immune-mediated inner ear disease was reported around 25 years ago, numerous attempts to identify the inner ear antigens have been performed. Experimental animal models have been used to study the immune mechanisms involved in hearing loss and to develop new therapies. Because animal models of autoimmune labyrinthitis have been developed by means of different antigens, we cannot yet show a valid immunopathologic explanation. A critical analysis of the more relevant experimental models employed has been performed in order to validate the methodology. Comparison between these models and animals with spontaneous systemic autoimmune disease has raised more questions concerning the pathophysiology of autoimmune hearing loss. A new pathogenetic theory is suggested, involving the supporting cells of the organ of Corti.

Animals↗

Sudden presentation of immune-mediated inner ear disease: characterization and acceptance of a cochleovestibular dysfunction.

Since the McCabe report, growing indirect evidence has accumulated to indicate the implication of immune mechanisms in the pathogenesis of immune-mediated inner-ear disease (IMIED). A clinical study of a group of patients affected by this condition was performed in order to characterize the immune group, based on a recently reported profile, and compared with the vascular, viral and idiopathic aetiologies of sudden deafness. Patients affected by immune-mediated inner-ear disease had the best and the earliest recovery rate of hearing (p = 0.0028 and p = 0.017, respectively). However, this group of patients also had the higher rate of recurrence (p = 0.034), supporting the typical clinical course of the autoimmune disorders. On the basis of the results the criteria used in the diagnosis of the sudden presentation of the immune-mediated inner ear disease could be accepted leading to the characterization of this condition. Likewise, the role of the supporting cells in the pathogenesis of the IMIED is discussed.

Adolescent↗

Role of thymic stromal cell dysfunction in the thymic involution of mammary tumor-bearing mice.

The growth of D1-DMBA-3 mammary tumors leads to a profound thymic atrophy in the hosts. In previous studies we have shown a minor increase in thymic apoptosis in tumor bearers and an early block in the maturation of double negative cells was observed in the thymuses of tumor-bearing mice. We now present evidence that in tumor bearers there is no increased apoptosis in the periphery that may enhance the migration of thymic precursors. Furthermore, using direct fluorescein labeling of thymocytes in vivo, no increased numbers of recent thymic emigrants could be detected. In addition, the thymic atrophy did not affect all thymus functions since the integrity of negative selection was preserved in tumor-bearing mice. Stromal cells derived from the thymuses from normal mice and tumor-bearers had decreased proliferation in the presence of culture supernatants from DA-3 cells, derived from the in vivo D1-DMBA-3 mammary tumors. Addition of known tumor derived factors to normal thymic stromal cells showed that, while granulocyte-macrophage colony stimulating factor and prostaglandin E2 did not cause any effects, phosphatidyl serine severely inhibited their proliferation. Importantly, we demonstrated that tumor bearers' stromal cells could not support the proliferation of thymuses from either normal or tumor-bearing mice, indicating that functional changes in the stromal cells may be involved in the abnormal thymic development occurring during mammary tumor development.

Adenocarcinoma↗