The vestibular calyceal junction is dismantled following subchronic streptomycin in rats and sensory epithelium stress in humans.

Hair cell (HC) loss by epithelial extrusion has been described to occur in the rodent vestibular system during chronic 3,3'-iminodipropionitrile (IDPN) ototoxicity. This is preceded by dismantlement of the calyceal junction in the contact between type I HC (HCI) and calyx afferent terminals. Here, we evaluated whether these phenomena have wider significance. First, we studied rats receiving seven different doses of streptomycin, ranging from 100 to 800 mg/kg/day, for 3-8 weeks. Streptomycin caused loss of vestibular function associated with partial loss of HCI and decreased expression of contactin-associated protein (CASPR1), denoting calyceal junction dismantlement, in the calyces encasing the surviving HCI. Additional molecular and ultrastructural data supported the conclusion that HC-calyx detachment precede HCI loss by extrusion. Animals allowed to survive after the treatment showed functional recuperation and rebuilding of the calyceal junction. Second, we evaluated human sensory epithelia obtained during therapeutic labyrinthectomies and trans-labyrinthine tumour excisions. Some samples showed abnormal CASPR1 label strongly suggestive of calyceal junction dismantlement. Therefore, reversible dismantlement of the vestibular calyceal junction may be a common response triggered by chronic stress, including ototoxic stress, before HCI loss. This may partly explain clinical observations of reversion in function loss after aminoglycoside exposure.

Pre- and intra-operative prognostic factors of facial nerve function in cerebellopontine angle surgery.

PURPOSE: The study assesses whether pre- and intraoperative factors linked to electromyography and direct electrical stimulation (DES) of facial nerve can predict facial nerve function in the short- (12 days) and long-term (1 year) after cerebellopontine angle (CPA) tumor resection. METHODS: 157 patients who underwent surgical resection of CPA tumors with facial nerve monitoring. Pre-operative factors (age, tumor size, pure tone average), surgical time and intra-operative parameters regarding facial function, minimum stimulation threshold (MST), compound muscle action potential (CMAP) and the difference between proximal and distal CMAP (DPDC) were evaluated. RESULTS: A correlation between tumor size, MST, CMAP and facial function in both short and long term was found. A higher grade of immediate facial paralysis corresponded to a higher risk of poor outcome after one year. A postoperative House-Brackmann (HB) score of V or VI was correlated with poor outcome in 88.8% and 93.8% of cases. A risk of HB 3 or more, in the long term, was correlated with a tumor size of 20.2 mm. Using an MST of 0.1 mA, for long-term predictions, sensitivity and specificity were 0.62 (95% CI 0.46-0.75) and 0.73 (95% CI 0.61-0.82), respectively. With a CMAP cut-off < 200 µV, for long-term prediction, sensitivity was 0.73 (95% CI 0.53-0.87) and specificity 0.73 (95% CI 0.55-0.85). CONCLUSION: The assessment based on the cut-offs described increases the ability to predict facial function. Improving predictive accuracy enables surgeons to address patients' expectations and to establish an intervention timeline for planning facial reanimation.

Exploratory study of an oral screening dysplasia program for HIV-infected men who have sex with men.

BACKGROUND: HIV-infected men who have sex with men (MSM) are at high risk to develop human papilloma virus (HPV)-related oropharyngeal cancer. The aim of our study was to assess the usefulness of a pilot oral dysplasia screening program and its correlation with an anal dysplasia screening program. METHODS: This was a prospective study with HIV-infected MSM. Oral and anal screenings were performed based on HPV determination, liquid cytology, direct and microscopy oral examinations, high-resolution anoscopy and biopsies, if necessary. RESULTS: A total of 103 patients were included. The mean age of the patients was 44.6 years, 55.3% were smokers, and 57.3% had a history of previous anal high-grade squamous intraepithelial lesions (HSILs). The prevalence of oral HPV infections was 14% (9% HPV-high risk), the prevalence of abnormal cytology was 25.2%, and in 4.8% of the patients, oral examinations showed suspicious HSILs. Oral microscopy did not detect additional lesions that visual inspection. Five oral biopsies were performed and the results were normal. No risk factors for oral HPV infections were identified. The prevalence of anal HPV infections was 88.3% (76.7% HPV-high risk), 52.9% of the patients had altered cytology, and in 45.6% anoscopy showed changes suggestive of HSILs. Seventy-two anal biopsies were performed, detecting 25 cases of HSILs (24.3%).A poor correlation was observed between oral and anal HPV infections (κ = 0.037). CONCLUSIONS: The prevalence of oral HPV infections, abnormal cytology and lesions in HIV-infected MSM was low, and their correlation with anal HPV-related lesions was slight. These results confirm the current barriers to oral dysplasia screening techniques.

Cromosomopatías y malformaciones congénitas en Cochabamba: un análisis epidemiológico a través de los cariotipos

Objetivos: Describir las características epidemiológicas de las alteraciones cromosómicas y de las malformaciones congénitas en Cochabamba. Métodos: Se incluyeron en el estudio 166 pacientes con sospecha de alteración cromosómica, referidos de hospitales de Cochabamba. A cada paciente se le realizó la anamnesis, exploración física y la prueba de cariotipo en muestra de sangre periférica. Resultados: De los 166 pacientes estudiados, 79 (48 %) tenían cariotipo sin alteración y 87 (52 %) tenían alguna anomalía cromosómica. La alteración más frecuente fue Síndrome de Down (34 %), seguido por Síndrome de Turner, (11 %), Síndrome de Edwards, (2 %), trisomía 22 (1 %) Klinefelter (1 %), Deleciones (2 %) o cromosoma marcador 5 (1 %). La distribución de pacientes entre 0 y 1 año con dismorfia congènita fue la siguiente: 10% de recién nacidos hasta 7 días, 20 % neonatos entre 8 y 28 días y 70 % de lactantes menores y mayores desde 28 días a un año. Dentro este grupo encontramos alteración cromosómica confirmada en 43 pacientes (62 %) y en 26 (38%) cariotipo sin alteración. La edad promedio de los padres de niños con Sd. de Down, fue mayor a 40 años y para los otros síndromes fue menor a 30 años. Conclusiones: Las cromosomopatías más frecuentes fueron el Sd. de Down, Sd. de Turner y Sd. de Edwards. La mayor parte de los cariotipos fueron con alteración completa o libre en los diferentes Síndromes. La edad de la madre y del padre y el número de abortos parecen ser un factor de riesgo para el Síndrome de Down, y para el Síndrome de Turner.

Objectives: to describe the epidemiological characteristics of chromosomal abnormalities and congenital malformations in Cochabamba. Methods: 166 patients with suspected chromosomal abnormalities referred from hospitals in Cochabamba were included in the study. Each patient underwent a medical history, physical examination, and chromosomal analysis using a peripheral blood sample. Results: Of the 166 patients studied, 79 (48%) had normal chromosomal results and 87 (52%) had some chromosomal abnormality. The most common abnormality was Down syndrome (34%), followed by Turner syndrome (11%), Edwards syndrome (2%), trisomy 22 (1%), Klinefelter syndrome (1%), deletions (2%), or marker chromosome 5 (1%). The distribution of patients between 0 and 1 year of age with congenital dysmorphism was as follows: 10% of newborns up to 7 days, 20% of neonates between 8 and 28 days, and 70% of infants from 28 days to one year. Within this group, confirmed chromosomal abnormalities were found in 43 patients (62%) and normal chromosomal results in 26 (38%). The average age of parents of children with Down syndrome was over 40 years, while for other syndromes it was under 30 years. Conclusions: The most frequent chromosomal disorders were Down syndrome, Turner syndrome, and Edwards syndrome. Most chromosomal results were complete or free of alteration in the different syndromes. The mother's and father's age and the number of abortions appear to be risk factors for Down syndrome, and for Turner syndrome.

CT Assessment of Otic Capsule Bone Density in Paget's Disease of the Temporal Bone and Its Relationship With Hearing Loss.

OBJECTIVES: To study computed tomography findings in Paget's disease of temporal bone (PDTB) and analyze the relations between otic capsule bone mineral density values measured in Hounsfield Units (HU) and hearing loss (HL). STUDY DESIGN: Observational case-control study. SETTING: Tertiary referral center. PATIENTS: Radiographically confirmed PDTB cases and control group. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Hearing thresholds and computed tomography bone density values. RESULTS: Twenty-three ears in the case group (PDTB) and 27 control ears were included. In the PDTB group, HL was found in 87% of the ears (43% mixed) and an air-conduction threshold of 50.7 dB (SD = 19.8). In the control group, 48% of the ears showed HL (7% mixed) and an air-conduction threshold of 34.5 dB (SD = 20.6) was found; the difference was statistically significant (p < 0.05). Measurements of bone density (HU) in the otic capsule (regions of interest [ROI] 1 and 2) and in the petrous bone (ROI 3) were significantly lower (p < 0.05) in the PDTB group than in controls.The PDTB group presented a significant association between otic capsule bone density in ROI 1 and mean otic capsule density with air and bone-conduction thresholds (p < 0.05). In controls, no association was observed between any density value and audiometric thresholds. CONCLUSION: PDTB patients showed more frequent HL, lower thresholds, and a higher proportion of mixed HL than controls. Bone density (HU) was decreased in all ROIs in PDTB patients in comparison with controls. Bone density in the otic capsule was associated with HL in PDTB patients, but no association was observed between bone density and HL in controls.

Linfoma de la zona marginal de glándula parótida / Marginal zone lymphoma of parotid gland

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Physiological assesment of vestibular function and toxicity in humans and animals.

Physiological methods that can be similarly recorded in humans and animals have a major role in sensory toxicology, as they provide a bridge between human sensory perception data and the molecular and cellular data obtained in animal studies. Vestibular toxicity research lags well behind other sensory systems in many aspects, including the availability of methods for functional assessment in animals that could be robustly translated to human significance. Here we review the methods available for the assessment of vestibular function in both humans and laboratory animals, with an emphasis on their similarity or divergence, to highlight their potential utility for the predictive assessment of vestibular toxicity.

Dose-dependent cochlear and vestibular toxicity of trans-tympanic cisplatin in the rat.

In vivo studies are needed to study cisplatin ototoxicity and to evaluate candidate protective treatments. Rats and mice are the preferred species for toxicological and pharmacological pre-clinical research, but systemic administration of cisplatin causes high morbidity in these species. We hypothesized that trans-tympanic administration of cisplatin would provide a good model for studying its auditory and vestibular toxicity in the rat. Cisplatin was administered by the trans-tympanic route in one ear (50µl, 0.5-2mg/ml) of rats of both sexes and two different strains. Cochlear toxicity was corroborated by histological means. Vestibular toxicity was demonstrated by behavioral and histological analysis. Cisplatin concentrations were assessed in inner ear after trans-tympanic and i.v. administration. In all experiments, no lethality and only scant body weight loss were recorded. Cisplatin caused dose-dependent cochlear toxicity, as demonstrated by hair cell counts in the apical and middle turns of the cochlea, and vestibular toxicity, as demonstrated by behavioral analysis and hair cell counts in utricles. High concentrations of cisplatin were found in the inner ear after trans-tympanic administration. In comparison, i.v. administration resulted in lower inner ear concentrations. We conclude that trans-tympanic administration provides an easy, reproducible and safe model to study the cochlear and vestibular toxicity of cisplatin in the rat. This route of exposure may be useful to address particular questions on cisplatin induced ototoxicity and to test candidate protective treatments.

Analysis of predisposing factors for complications of percutaneous tracheostomy.

Since the turn of the century, percutaneous tracheostomy (PT) has become an alternative to the classic open technique and is an elective procedure in intensive care units at most centers. We conducted a prospective study to identify and quantify the complication rate with PT and to analyze this procedure's association with potential risk factors. Our study population was made up of 114 patients-83 men (72.8%) and 31 women (27.2%), aged 18 to 81 years (mean: 57 ± 15)-who underwent PT at our center over an 18-month period. We sought to determine if there were any associations between PT complications and sex, previous fibroscopy, cervical length, cervical risk factors, and general risk factors. Generally minor complications were noted in 15 patients (13.2%); 13 patients experienced hemorrhage, 1 exhibited subcutaneous emphysema, and 1 had a vagal reaction that resolved with medical treatment. Only 3 of these cases (2.6%) were considered to be clinically relevant: 1 hemorrhage (which was treated with ligation), the emphysema (which resolved spontaneously), and the vagal reaction (which resolved with medical treatment). Statistically, we found that PT complications were significantly correlated with two factors: coagulopathy (p = 0.015) and hemodynamic instability (p = 0.017). Even so, these complications were not clinically significant, and they resolved with conservative treatment measures. Given the low incidence and mild degree of these complications, we consider PT to be a safe procedure, even in patients with a high risk of hemorrhage or cervical anatomic difficulties.

Cisplatin-Induced Ototoxicity: Effects, Mechanisms and Protection Strategies.

Cisplatin is a highly effective chemotherapeutic agent that is widely used to treat solid organ malignancies. However, serious side effects have been associated with its use, such as bilateral, progressive, irreversible, dose-dependent neurosensory hearing loss. Current evidence indicates that cisplatin triggers the production of reactive oxygen species in target tissues in the inner ear. A variety of agents that protect against cisplatin-induced ototoxicity have been successfully tested in cell culture and animal models. However, many of them interfere with the therapeutic effect of cisplatin, and therefore are not suitable for systemic administration in clinical practice. Consequently, local administration strategies, namely intratympanic administration, have been developed to achieve otoprotection, without reducing the antitumoral effect of cisplatin. While a considerable amount of pre-clinical information is available, clinical data on treatments to prevent cisplatin ototoxicity are only just beginning to appear. This review summarizes clinical and experimental studies of cisplatin ototoxicity, and focuses on understanding its toxicity mechanisms, clinical repercussions and prevention strategies.

Cocleotoxicidad por cisplatino en un modelo experimental / Cisplatin cochlear toxicity in an experimental model

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Resultados en el tratamiento quirúrgico de los neurinomas del acústico gigantes / Results in the surgical treatment of giant acoustic neuromas

Introducción y objetivos: Comparar los resultados obtenidos en la resección de 21 schwanomas vestibulares gigantes, mediante vía retrosigmoidea y combinada retrosigmoidea/translaberíntica en cuanto a complicaciones intra y postoperatorias, preservación del nervio facial y secuelas posquirúrgicas. Métodos: Se realiza un estudio retrospectivo de 21 pacientes a los que se practicó resección de neurinoma vestibular gigante según la escala de Tos & Thomsen (igual o mayor a 4cm), en un hospital de tercer nivel en el periodo entre 2000 y 2008. Se presentan las características más significativas de la serie estudiada, y se analizan las ventajas e inconvenientes de los distintos abordajes, comparando los resultados obtenidos. Asimismo, se analizan los resultados en cuanto a la preservación de la función del nervio facial. Resultados: Destaca la ausencia de mortalidad en el grupo de 21 pacientes estudiado. No hubo complicaciones intraoperatorias importantes. Se consiguió la resección total de la lesión en el 87% de los casos, con una preservación anatómica del nervio facial del 73% en el abordaje combinado retrosigmoideo/translaberíntico, respecto a un 40% en el retrosigmoideo. La función del nervio facial a los dos años fue aceptable o buena en un 67% (incluyendo los resultados de las anastomosis heteronerviosas). Se observó un porcentaje global del 14,3% de fístula de líquido cefalorraquídeo y un 9,5% de meningitis. Conclusiones: nuestros resultados demuestran que el abordaje combinado retrosigmoideo translaberíntico para el tratamiento de schwannomas gigantes ofrece mayor preservación del nervio facial y disminución de la morbilidad, siendo una importante opción en el tratamiento de estos tumores, gracias a un enfoque multidisciplinar(AU)

Introduction and objectives: To compare the results obtained in the resection of 21 giant vestibular schwannomas via retrosigmoid (RS) and combined retrosigmoid/translabyrinthine (RS/TL) approaches with respect to intra- and postoperative complications, facial nerve preservation and postsurgical sequelae. Methods: This was a retrospective study of 21 patients who underwent a resection of a giant vestibular neuroma according to the Tos & Thomsen Scale (greater than or equal to 4 centimetres) in a tertiary care centre in the period between 2000 and 2008. We present the most significant characteristics of the series studied and the analysis of the advantages and inconveniences of each approach. We also analyse the results regarding facial nerve function preservation. Results: We highlight the absence of mortality in the 21-patient group. There were no important intraoperative complications. Total resection of the lesion was achieved in the 87% of the cases, with facial nerve preservation of 73% using the combined RS/TL approach, in comparison to 40% using the RS. Facial nerve function after two years was acceptable or good in 67% (including those with heteronerve anastomosis). A global percentage of 14.3% of cerebrospinal liquid fistula was observed, as well as 9.5% of meningitis. Conclusions: The results of the study demonstrate that the combined retrosigmoid translabyrinthine approach for giant schwannoma treatment offers increased facial nerve preservation and lower morbidity, constituting an important option in the treatment of this kind of tumours thanks to a multidisciplinary approach(AU)

[Results in the surgical treatment of giant acoustic neuromas]. / Resultados en el tratamiento quirúrgico de los neurinomas del acústico gigantes.

INTRODUCTION AND OBJECTIVES: To compare the results obtained in the resection of 21 giant vestibular schwannomas via retrosigmoid (RS) and combined retrosigmoid/translabyrinthine (RS/TL) approaches with respect to intra- and postoperative complications, facial nerve preservation and postsurgical sequelae. METHODS: This was a retrospective study of 21 patients who underwent a resection of a giant vestibular neuroma according to the Tos & Thomsen Scale (greater than or equal to 4 centimetres) in a tertiary care centre in the period between 2000 and 2008. We present the most significant characteristics of the series studied and the analysis of the advantages and inconveniences of each approach. We also analyse the results regarding facial nerve function preservation. RESULTS: We highlight the absence of mortality in the 21-patient group. There were no important intraoperative complications. Total resection of the lesion was achieved in the 87% of the cases, with facial nerve preservation of 73% using the combined RS/TL approach, in comparison to 40% using the RS. Facial nerve function after two years was acceptable or good in 67% (including those with heteronerve anastomosis). A global percentage of 14.3% of cerebrospinal liquid fistula was observed, as well as 9.5% of meningitis. CONCLUSIONS: The results of the study demonstrate that the combined retrosigmoid translabyrinthine approach for giant schwannoma treatment offers increased facial nerve preservation and lower morbidity, constituting an important option in the treatment of this kind of tumours thanks to a multidisciplinary approach.