La azatioprina reduce el riesgo de recaída audiométrica en hipoacusia inmunomediada / Azathioprine reduces the risk of audiometric relapse in immune-mediated hearing loss

INTRODUCCIÓN: Los esquemas actuales de tratamiento de la hipoacusia inmunomediada con corticoides, dosis baja y pauta corta, son insuficientes. MÉTODOS: Para determinar el papel de la azatioprina en el control del deterioro auditivo se ha llevado a cabo un estudio observacional descriptivo longitudinal con 20 pacientes tratados con azatioprina por vía oral (1,5-2,5 mg/kg/día en dos dosis) durante 1año. Se consideró recaída la pérdida de 10 dB en dos frecuencias consecutivas o de 15 dB en una frecuencia aislada. RESULTADOS: La edad media de los pacientes fue de 52,50 años (IC 95%: 46,91-58,17), y la mitad fueron mujeres. La afectación bilateral fue del 65%. Un 75% presentaban enfermedad organoespecífica y un 25%, enfermedad autoinmune sistémica. La diferencia entre la PTA basal (46,49 dB; DE18,90) y la PTA a los 12meses (45,47 dB; DE 18,88) no alcanzó significación estadística (p = 0,799). Existía una correlación positiva moderada entre sexo femenino y presencia de enfermedad sistémica (R = 0,577). Aplicando t de Student para datos apareados se obtuvo una diferencia significativa (p = 0,042) entre el descenso de la PTA en frecuencias hasta 1.000Hz (PTA125-1.000Hz). La tasa relativa de incidencia de recaída por año fue de 0,52 recaídas/año (IC 95%: 0,19-1,14). El tiempo medio de supervivencia libre de recaída audiométrica fue de 9,70 meses (DE 1,03). CONCLUSIONES: La azatioprina mantiene el umbral de audición, disminuye el riesgo de recaída y frena la velocidad con la que los pacientes recaen, alterando el curso de la enfermedad inmunomediada del oído interno

INTRODUCTION: Current schemes for treatment of immune-mediated hearing loss with sporadic short-course, low-dose corticosteroids, are insufficient. METHODS: To determine the role of azathioprine in the control of auditory impairment, a longitudinal, observational, descriptive study was performed with 20 patients treated with azathioprine (1.5-2.5 mg/kg/day into two doses) for 1year. The loss of 10 dB on two consecutive frequencies or 15 dB on an isolated frequency was considered as relapse. RESULTS: The mean age of the patients was 52.50 years (95% CI: 46.91-58.17), half were women. Bilateral affectation was 65%. 75% had organ specific disease and 25% had systemic autoimmune disease. The difference between baseline PTA (46.49 dB; DS 18.90) and PTA at 12 months (45.47dB; DS 18.88) did not reach statistical significance (P = .799). There was a moderate positive correlation between female sex and the presence of systemic disease (R = .577). By applying Student's t for paired data, a significant difference (P = .042) was obtained between the PTA in frequencies up to 1000 Hz (PTA125-1000Hz). The relative incidence rate of relapse per year was .52 relapses/year (95% CI: .19-1.14]). The median time to audiometric relapse-free was 9.70 months (DS 1.03). CONCLUSIONS: Azathioprine maintains the hearing threshold, decreases the risk of relapse, and slows down the rate at which patients relapse, altering the course of immune-mediated inner ear disease

Análisis de supervivencia libre de recaída audiométrica en pacientes con hipoacusia inmunomediada tratados exclusivamente con corticoides / Analysis of audiometric relapse-free survival in patients with immune-mediated hearing loss exclusively treated with corticosteroids

OBJETIVO: Describir los resultados en términos de supervivencia libre de recaída audiométrica y el ritmo de recaída en pacientes con hipoacusia inmunomediada tratados exclusivamente con corticoides. MÉTODO: Estudio retrospectivo de pacientes, con recaídas audiométricas, en seguimiento desde 1995 hasta 2014, en 2 centros de la Comunidad de Madrid. RESULTADOS: Se evaluaron 31 pacientes con una media de edad de 48,52 años (14,67 DE) de los cuales el 61,3% fueron mujeres. La mayoría de las hipoacusias fueron fluctuantes (48,4%). Solo el 16,1% de los pacientes presentaban enfermedad autoinmune sistémica. Existe una correlación positiva moderada entre ser mujer y presentar afectación sistémica (coeficiente de correlación de Spearman = 0,356). La tasa relativa de incidencia de recaída en el primer año en nuestra serie fue de 2,01 recaídas/año con un IC95% (1,32-2,92). El tiempo de supervivencia medio del evento (recaída audiométrica) fue de 5,25 meses (DE 0,756). Con el análisis multivariante, la única variable que consiguió significación estadística fue la edad, con una hazard ratio de 1,032 (IC95%; 1,001-1,063, p = 0,043). CONCLUSIONES: La enfermedad inmunomediada del oído interno es una enfermedad crónica con recaídas. La mitad de los pacientes tratados exclusivamente con corticoides recaen antes de los 6 meses de seguimiento. Además, si un paciente no ha presentado recaída, tiene más riesgo de recaer cada año que pasa. El análisis de la supervivencia libre de recaída audiométrica permitirá comparar el efecto de tratamientos futuros y su capacidad para reducir el ritmo de recaídas

OBJECTIVE: To describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids. METHOD: Retrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid. RESULTS: We evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient = 0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001-1.063, P = .043). CONCLUSIONS: Immune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the of audiometric relapse- free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses

Azathioprine reduces the risk of audiometric relapse in immune-mediated hearing loss. / La azatioprina reduce el riesgo de recaída audiométrica en hipoacusia inmunomediada.

INTRODUCTION: Current schemes for treatment of immune-mediated hearing loss with sporadic short-course, low-dose corticosteroids, are insufficient. METHODS: To determine the role of azathioprine in the control of auditory impairment, a longitudinal, observational, descriptive study was performed with 20 patients treated with azathioprine (1.5-2.5mg/kg/day into two doses) for 1year. The loss of 10dB on two consecutive frequencies or 15dB on an isolated frequency was considered as relapse. RESULTS: The mean age of the patients was 52.50years (95%CI: 46.91-58.17), half were women. Bilateral affectation was 65%. 75% had organ specific disease and 25% had systemic autoimmune disease. The difference between baseline PTA (46.49dB; DS18.90) and PTA at 12months (45.47dB; DS18.88) did not reach statistical significance (P=.799). There was a moderate positive correlation between female sex and the presence of systemic disease (R=.577). By applying Student's t for paired data, a significant difference (P=.042) was obtained between the PTA in frequencies up to 1000 Hz (PTA125-1000Hz). The relative incidence rate of relapse per year was .52 relapses/year (95%CI: .19-1.14]). The median time to audiometric relapse-free was 9.70months (DS1.03). CONCLUSIONS: Azathioprine maintains the hearing threshold, decreases the risk of relapse, and slows down the rate at which patients relapse, altering the course of immune-mediated inner ear disease.

pH-sensitive polymeric nanoparticles with antioxidant and anti-inflammatory properties against cisplatin-induced hearing loss.

Polymeric nanoparticles (NPs) based on smart synthetic amphiphilic copolymers are used to transport and controlled release dexamethasone in the inner ear to protect against the ototoxic effect of cisplatin. The NPs were based on a mixture of two pseudo-block polymer drugs obtained by free radical polymerization: poly(VI-co-HEI) and poly(VP-co-MVE) or poly(VP-co-MTOS), being VI 1-vinylimidazole, VP N-vinylpyrrolidone, and HEI, MVE and MTOS the methacrylic derivatives of ibuprofen, α-tocopherol and α-tocopheryl succinate, respectively. The NPs were obtained by nanoprecipitation with appropriate hydrodynamic properties, and isoelectric points that matched the pH of inflamed tissue. The NPs were tested both in vitro (using HEI-OC1 cells) and in vivo (using a murine model) with good results. Although the concentration of dexamethasone administered in the NPs is around two orders of magnitude lower that the conventional treatment for intratympanic administration, the NPs protected from the cytotoxic effect of cisplatin when the combination of the appropriate properties in terms of size, zeta potential, encapsulation efficiency and isoelectric point were achieved. To the best of our knowledge this is the first time that pH sensitive NPs are used to protect from cisplatin-induced hearing loss by intratympanic administration.

Analysis of audiometric relapse-free survival in patients with immune-mediated hearing loss exclusively treated with corticosteroids. / Análisis de supervivencia libre de recaída audiométrica en pacientes con hipoacusia inmunomediada tratados exclusivamente con corticoides.

OBJECTIVE: To describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids. METHOD: Retrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid. RESULTS: We evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient=0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001-1.063, P=.043). CONCLUSIONS: Immune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the of audiometric relapse- free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses.

Polymeric nanoparticles loaded with dexamethasone or α-tocopheryl succinate to prevent cisplatin-induced ototoxicity.

The aim of this work is the development of highly protective agents to be administered locally within the middle ear to avoid cisplatin-induced ototoxicity, which affects to 100% of the clinical patients at ultra-high concentrations (16mg/kg). The protective agents are based on polymeric nanoparticles loaded with dexamethasone or α-tocopheryl succinate as anti-inflammarory and anti-apoptotic molecules. Dexamethasone and α-tocopheryl succinate are poorly soluble in water and present severe side effects when systemic administered during long periods of time. Their incorporation in the hydrophobic core of nanoparticles with the appropriate hydrodynamic properties provides the desired effects in vitro (lower cisplatin-induced toxicity, decreasing of caspase 3/7 activity, and lower IL-1ß release) and in vivo (reducing the hearing loss at the local level). The local administration of the nanoparticles by bullostomy provides an adequate dose of drug without systemic interference with the chemotherapeutic effect of cisplatin. STATEMENT OF SIGNIFICANCE: 100% of the cancer patients receiving ultra-high doses of CDDP (16mg/kg) suffer severe hearing loss, being a limiting factor in antineoplastic treatments. In this paper we describe the application of polymeric nanoparticles loaded with dexamethasone or α-tocopheryl succinate to palliate the cisplatin ototoxicity derived from chemotherapy treatment. These new nanoparticles, that encapsulate, transport, and deliver dexamethasone or α-tocopheryl succinate in the middle ear, are able to partially prevent ototoxicity derived from high doses of CDDP. This is an interdisciplinary study in which in vitro and in vivo experiments are described and extensively discussed. The importance of the results opens an excellent opportunity to the translation to the clinic.

Spontaneous Cannabinoid Receptor 2 (CB2) Expression in the Cochlea of Adult Albino Rat and Its Up-Regulation after Cisplatin Treatment.

We provide evidence for the presence of cannabinoid CB2 receptors in some cellular types of the cochlea of the adult albino rat. Cannabinoids and their receptors are increasingly being studied because of their high potential for clinical use. As a hyperspecialized portion of the peripheral nervous system, study of the expression and function of cannabinoid receptors in the hearing organ is of high interest. Stria vascularis and inner hair cells express CB2 receptor, as well as neurites and cell bodies of the spiral ganglion. Cellular types such as supporting cells and outer hair cells, in which the expression of other types of functional receptors has been reported, do not significantly express CB2 receptors in this study. An up-regulation of CB2 gene expression was detected after an ototoxic event such as cisplatin treatment, probably due to pro-inflammatory events triggered by the drug. That fact suggests promising potential of CB2 receptor as a therapeutic target for new treatments to palliate cisplatin-induced hearing loss and other ototoxic events which triggers inflammatory pathways.

Otoprotective properties of 6α-methylprednisolone-loaded nanoparticles against cisplatin: In vitro and in vivo correlation.

6α-Methylprednisolone-loaded surfactant-free nanoparticles have been developed to palliate cisplatin ototoxicity. Nanoparticles were based on two different amphiphilic pseudo-block copolymers obtained by free radical polymerization and based on N-vinyl pyrrolidone and a methacrylic derivative of α-tocopheryl succinate or α-tocopherol. Copolymers formed spherical nanoparticles by nanoprecipitation in aqueous media that were able to encapsulate 6α-methylprednisolone in their inner core. The obtained nanovehicles were tested in vitro using HEI-OC1 cells and in vivo in a murine model. Unloaded nanoparticles were not able to significantly reduce the cisplatin ototoxicity. Loaded nanoparticles reduced cisplatin-ototoxicity in vitro being more active those based on the methacrylic derivative of vitamin E, due to their higher encapsulation efficiency. This formulation was able to protect hair cells in the base of the cochlea, having a positive effect in the highest frequencies tested in a murine model. A good correlation between the in vitro and the in vivo experiments was found. FROM THE CLINICAL EDITOR: Cisplatin is a commonly used chemotherapeutic agent against many cancers clinically. However, one of the significant side-effects remains ototoxicity. Here, the authors presented their data on using 6α-methylprednisolone-loaded nanoparticles in the reduction of ototoxicity in in-vitro and in-vivo experiments. Early promising results should enable further refinement of adopting this new approach in future experiments.

Noncholesteatomatous Cyst of the Tympanic Membrane: A Nonpublished Entity?

Introduction. The presence of a serous cyst in the tympanic membrane implies the description of a new or unpublished entity based on our knowledge whose origin may be very unlikely explained on actual embryologic and anatomic background. Clinical Case. We present a case of a 45-year-old woman with progressing right hearing loss. Physical examination revealed a whitish, round-shaped malformation in the posterior-inferior quadrant of the right tympanic membrane. The cyst was removed with a transcanal tympanoplasty. Discussion. A thorough PubMed search that involved the terms tympanic membrane gland, epithelial inclusion cysts, mucous-secreting cyst, and tympanic cyst has shown no positive results. The first description of an unknown entity, such as a tympanic membrane serous cyst, may be the key for clinicians to start paying attention to patients who suffer from similar pathologies and may pass unnoticed because of their rarity or peculiarity.

New prospects in the diagnosis and treatment of immune-mediated inner ear disease.

Autoimmune inner ear disease (AIED) represents a very fertile research field and the advancements in the understanding of this disease have a direct application not only in patients affected with this condition but also in other inner ear disorders that share the same injury mechanism, damage to the inner ear hair cells. AIED also presents many challenges that have still to be overcome. Firstly, access to the inner ear is limited, as many interventions such as biopsies can result in great irreversible damage. Secondly, there are no completely specific markers for AIED. Lack of a definitive diagnosis can result in the treatment of patients not affected with the disease and, therefore, no response. Finally, some patients become refractory to glucocorticoids and new therapies are needed. This review offers an overview of the animal models that have contributed to the understanding of AIED pathophysiology, the value of currently available diagnostic tests, and therapeutic options, with a special focus on new therapies for non responders or patients refractory to glucocorticoids. Among these new options for therapy, biological agents have been tested recently, whereas gene and stem cell therapy may have a role in the future. The intratympanic route of administration avoids the systemic side effects associated with currently used drugs, and may become a more frequent approach in the future.

Hemangiopericytoma of the parapharyngeal space: a diagnostic challenge.

Parapharyngeal space tumors are known for having a difficult approach, misleading diagnosis and for representing a treatment challenge. Hemangiopericytomas account for less than 1% of all vascular neoplasms and 3% of all soft tissue sarcomas. Only 14 cases have been reported in the worldwide literature in this location. We present a case of a 44-year-old male who was referred for evaluation. A CT scan and MRI showed a large parapharyngeal mass of a possible salivary gland origin. The patient underwent a lateral cervicotomy associated with a transparotid-transmandibular approach, obtaining a vimentin-positive immunostaining tumor defining the diagnosis. The accurate management and prognosis of this type of neoplasm are provided by the definite diagnosis obtained by a correct histopathologic assessment. A high clinical suspicion is essential.

Revisión de las terapias biológicas en la enfermedad inmunomediada del oído interno / Review of the biologic agents used for immune-mediated inner ear disease

Introducción y objetivos: La enfermedad inmunomediada del oído interno (EIOI) es una de las escasas afecciones del oído interno que pueden revertirse con tratamiento médico. Este se basa en los corticoides, si bien el tratamiento prolongado con los mismos se asocia a serios efectos adversos, lo que ha propiciado el uso de otros fármacos o vías de administración como la intratimpánica. En este estudio se analiza el papel de las terapias biológicas en el tratamiento de la EIOI. Material y métodos: Se ha realizado una búsqueda sistemática en PUBMED de aquellos estudios que examinan la respuesta al tratamiento con distintos agentes biológicos en pacientes con EIOI. Se ha analizado los criterios de inclusión y exclusión de cada estudio, así como las características de la población estudiada, el tratamiento utilizado y, los criterios de respuesta y tasa de respuesta alcanzada. Resultados: Se identificaron 13 estudios relevantes. En 8 estudios se utilizó un inhibidor del TNFα (etanercept, infliximab, adalimumab), en 3 un antagonista de la IL-1 (anakinra) y en el resto se empleó el rituximab, un antagonista del receptor CD20 de los linfocitos B. En la mayoría de los estudios se logró una mejoría o estabilización de la audición en más del 70% de los pacientes tratados. Conclusiones: Las terapias biológicas pueden tener un papel en el tratamiento de los pacientes con EIOI, al menos en aquellos que responden mal a los corticoides o no se consigue su estabilización. Sin embargo, son necesarios más estudios controlados y aleatorizados para conocer su eficacia (AU)

Introduction and objectives: Immune-mediated inner ear disease (IMIED) is one of the few reversible forms of sensorineural hearing loss. Treatment is based on high-dose corticosteroids, although long-term therapy is associated with serious adverse effects; this has led to the use of other agents or different routes of administration such as transtympanic delivery. This study analyses the role of biological agents in IMIED management. Material and methods: We searched PUBMED for studies that examined the response to treatment with different biological agents in patients with IMIED. The following data were extracted from the selected studies and entered into a standardised database: exclusion and inclusion criteria, characteristics of the patients studied, treatment, outcome measures and response rates achieved. Results: Thirteen studies were included in this review. A TNF alpha inhibitor (etanercept, infliximab, adalimumab) was used in 8 studies, an IL-1 antagonist (anakinra) was used in 3 studies and rituximab, an antibody directed against the CD20 surface antigen on B lymphocytes, was evaluated in 2 studies. Most studies achieved a hearing improvement or stabilisation in more than 70% of treated patients. Conclusions: Biological agents can play a role in the management of patients with IMIED, at least in those patients who do not respond to conventional therapy or whose hearing is not stabilised. However, specially-designed randomised controlled clinical trials are needed to assess their effectiveness (AU)

Review of the biologic agents used for immune-mediated inner ear disease.

INTRODUCTION AND OBJECTIVES: Immune-mediated inner ear disease (IMIED) is one of the few reversible forms of sensorineural hearing loss. Treatment is based on high-dose corticosteroids, although long-term therapy is associated with serious adverse effects; this has led to the use of other agents or different routes of administration such as transtympanic delivery. This study analyses the role of biological agents in IMIED management. MATERIAL AND METHODS: We searched PUBMED for studies that examined the response to treatment with different biological agents in patients with IMIED. The following data were extracted from the selected studies and entered into a standardised database: exclusion and inclusion criteria, characteristics of the patients studied, treatment, outcome measures and response rates achieved. RESULTS: Thirteen studies were included in this review. A TNF alpha inhibitor (etanercept, infliximab, adalimumab) was used in 8 studies, an IL-1 antagonist (anakinra) was used in 3 studies and rituximab, an antibody directed against the CD20 surface antigen on B lymphocytes, was evaluated in 2 studies. Most studies achieved a hearing improvement or stabilisation in more than 70% of treated patients. CONCLUSIONS: Biological agents can play a role in the management of patients with IMIED, at least in those patients who do not respond to conventional therapy or whose hearing is not stabilised. However, specially-designed randomised controlled clinical trials are needed to assess their effectiveness.

Reactive oxygen species in apoptosis induced by cisplatin: review of physiopathological mechanisms in animal models.

Cisplatin is a highly effective chemotherapeutic agent but displays significant ototoxic side effects. The most prominent change seen in the cochlea after cisplatin administration consists of loss of outer hair cells. Several mechanisms are believed to mediate cisplatin-induced apoptosis: binding of cisplatin to guanine bases on DNA and the formation of inter- and intra-strand chain cross-linking, generation of reactive oxygen species (ROS) with increased lipid peroxidation and Ca(2+) influx and, finally, inflammation mediated by cisplatin. The aim of the present review is to analyze the role of ROS in the mechanisms causing cisplatin-mediated apoptosis in the inner ear and the contribution of the different pathways involved, emphasizing the main strategies to blockade events leading to apoptosis of cochlear cells.

Patient-derived olfactory mucosa cells but not lung or skin fibroblasts mediate axonal regeneration of retinal ganglion neurons.

Although human olfactory mucosa derived cells (OMC) have been used in animal models and clinical trials with CNS repair purposes, the exact identity of these cells in culture with respect to their tissue of origin is not fully understood and their neuroregenerative capacity in vitro has not yet been demonstrated. In this study we have compared human OMC with human ensheathing glia from olfactory bulb (OB) and human fibroblasts from skin and lung. Our results indicate that these different cultured cell types exhibit considerable overlap of antigenic markers such that it is presently not possible to distinguish them immunocytochemically. However, in rat retinal ganglion neuron coculture assays the axonal regenerative activity of OMC and OB ensheathing glia was dramatically higher than that exhibited by all fibroblast samples, confirming neuroregenerative activity as a unique property shared by cultured cells derived from the human olfactory system.

Resultados de 12 años de dacriocistorrinostomía endoscópica / Results of 12 years of endoscopic dacryocystorhinostomy

Introducción y objetivos: La inflamación crónica del conducto lacrimonasal con la consiguiente obstrucción del flujo de la lágrima es llamada dacriocistitis crónica. Mediante la dacriocistorrinostomía por vía endoscópica, es posible resolver esta obstrucción poniendo en comunicación el saco lacrimal directamente con la luz de la fosa nasal, sin cicatrices externas y de una forma relativamente sencilla y segura. Métodos: Se realiza una revisión de los casos intervenidos mediante esta técnica entre enero de 1996 y junio de 2008. Se estudian las características epidemiológicas de los pacientes, así como los resultados obtenidos, tanto en mejoría sintomática (subjetiva) como en mejoría del drenaje comprobada por el cirujano a la exploración (objetiva). Resultados: Un total de 76 dacriocistorrinostomías fueron realizadas en este período. De ellas, el 75% se trataba de pacientes mujeres. La edad media fue de 52,4 años. En un 80,3% de las intervenciones el paciente refería mejoría (total o parcial) de los síntomas, lo que se asemeja a los resultados arrojados por otras series. Conclusiones: La dacriocistorrinostomía realizada por vía endoscópica endonasal constituye una técnica sencilla y segura para el tratamiento de la dacriocistitis crónica, aportando unas tasas de curación/mejoría similares o superiores a las de otras técnicas. Las tasas de mejoría observadas en nuestra serie coinciden con las observadas en otros estudios (AU)

Introduction: Chronic inflammation of nasolacrimal duct determines obstruction of the lacrimal flow and is called chronic dacryocystitis. Endoscopic dacryocystorhinostomy (DCR) can solve this obstruction by opening the lacrimal sac directly to the nasal cavity, avoiding external scars in a simple, safe way. Material and method: We reviewed all cases operated using this technique between January 1996 and June 2008. We focused on demographic characteristics as well as the results obtained (subjective and objective improvements). Results: We reviewed 76 Endoscopic DCR that were performed during aforementioned period of time. Of these cases, 75% were females; mean age was 52.4 years old. Improvement in symptoms was reported by 80.3% of the patients. These data are similar to the results seen in other studies. Conclusions: Endoscopic dacryocystorhinostomy is a simple, safe technique for treating chronic dacryocystitis, which provides similar or even better rates of improvement than other techniques used for this condition. In our patients, the results are not different from those observed in other studies. Our outcomes are comparable to those observed in other studies (AU)

[Results of 12 years of endoscopic dacryocystorhinostomy]. / Resultados de 12 años de dacriocistorrinostomía endoscópica.

INTRODUCTION: Chronic inflammation of nasolacrimal duct determines obstruction of the lacrimal flow and is called chronic dacryocystitis. Endoscopic dacryocystorhinostomy (DCR) can solve this obstruction by opening the lacrimal sac directly to the nasal cavity, avoiding external scars in a simple, safe way. MATERIAL AND METHOD: We reviewed all cases operated using this technique between January 1996 and June 2008. We focused on demographic characteristics as well as the results obtained (subjective and objective improvements). RESULTS: We reviewed 76 Endoscopic DCR that were performed during aforementioned period of time. Of these cases, 75% were females; mean age was 52.4 years old. Improvement in symptoms was reported by 80.3% of the patients. These data are similar to the results seen in other studies. CONCLUSIONS: Endoscopic dacryocystorhinostomy is a simple, safe technique for treating chronic dacryocystitis, which provides similar or even better rates of improvement than other techniques used for this condition. In our patients, the results are not different from those observed in other studies. Our outcomes are comparable to those observed in other studies.

Ginkgo biloba extract (EGb761) protects against aging-related caspase-mediated apoptosis in rat cochlea.

CONCLUSIONS: EGb761 treatment has a significant benefit with an early and preventive effect, reversing the deleterious effect of aging in the integrity of the rat cochlea, even in the late stage of the rat lifespan. OBJECTIVES: We previously reported a significant relationship between aging and apoptosis in the rat cochlea. This study was designed to investigate the effects of Ginkgo biloba leaf extract (EGb761) on age-associated cochlear caspase activation. METHODS: Sprague-Dawley rats (n = 80) divided into two groups according to their age (4 months old, younger, YR, and 12 months old, aged-mature, AM) were treated with 100 mg/kg/day body weight of EGb761 extract dissolved in tap water for two periods: 4 and 12 months. Then cochleae were harvested to measure caspase activities, ATP levels, total superoxide dismutase (SOD) activity, and caspase-3 gene expression. Auditory steady-state responses (ASSR) threshold shifts were also measured before sacrifice of the rats. RESULTS: EGb761 treatment prevents significantly aging-related caspase-induced activities within the cochleae in YR and AM rats. In the short EGb761 treatment, YR rats showed lower levels of caspase-3/7 than AM rats. In contrast, longer treatment did not show significant differences between YR and AM rats. Reduced caspase-3/7 activity in presence of EGb761 correlates with significant improvements of ASSR threshold shifts.