Skin-associated lactic acid bacteria from North American bullfrogs as potential control agents of Batrachochytrium dendrobatidis.

The fungal pathogen Batrachochytrium dendrobatidis (Bd) is the causative agent of chytridiomycosis and has been a key driver in the catastrophic decline of amphibians globally. While many strategies have been proposed to mitigate Bd outbreaks, few have been successful. In recent years, the use of probiotic formulations that protect an amphibian host by killing or inhibiting Bd have shown promise as an effective chytridiomycosis control strategy. The North American bullfrog (Lithobates catesbeianus) is a common carrier of Bd and harbours a diverse skin microbiota that includes lactic acid bacteria (LAB), a microbial group containing species classified as safe and conferring host benefits. We investigated beneficial/probiotic properties: anti-Bd activity, and adhesion and colonisation characteristics (hydrophobicity, biofilm formation and exopolysaccharide-EPS production) in two confirmed LAB (cLAB-Enterococcus gallinarum CRL 1826, Lactococcus garvieae CRL 1828) and 60 presumptive LAB (pLAB) [together named as LABs] isolated from bullfrog skin.We challenged LABs against eight genetically diverse Bd isolates and found that 32% of the LABs inhibited at least one Bd isolate with varying rates of inhibition. Thus, we established a score of sensitivity from highest (BdGPL AVS7) to lowest (BdGPL C2A) for the studied Bd isolates. We further reveal key factors underlying host adhesion and colonisation of LABs. Specifically, 90.3% of LABs exhibited hydrophilic properties that may promote adhesion to the cutaneous mucus, with the remaining isolates (9.7%) being hydrophobic in nature with a surface polarity compatible with colonisation of acidic, basic or both substrate types. We also found that 59.7% of LABs showed EPS synthesis and 66.1% produced biofilm at different levels: 21% weak, 29% moderate, and 16.1% strong. Together all these properties enhance colonisation of the host surface (mucus or epithelial cells) and may confer protective benefits against Bd through competitive exclusion. Correspondence analysis indicated that biofilm synthesis was LABs specific with high aggregating bacteria correlating with strong biofilm producers, and EPS producers being correlated to negative biofilm producing LABs. We performed Random Amplified Polymorphic DNA (RAPD)-PCR analysis and demonstrated a higher degree of genetic diversity among rod-shaped pLAB than cocci. Based on the LAB genetic analysis and specific probiotic selection criteria that involve beneficial properties, we sequenced 16 pLAB which were identified as Pediococcus pentosaceus, Enterococcus thailandicus, Lactobacillus pentosus/L. plantarum, L. brevis, and L. curvatus. Compatibility assays performed with cLAB and the 16 species described above indicate that all tested LAB can be included in a mixed probiotic formula. Based on our analyses, we suggest that E. gallinarum CRL 1826, L. garvieae CRL 1828, and P. pentosaceus 15 and 18B represent optimal probiotic candidates for Bd control and mitigation.

Novel approaches in primary cardiovascular disease prevention: the HOPE-3 trial rationale, design, and participants' baseline characteristics

AbstractBACKGROUND:Cholesterol and blood pressure (BP) can be effectively and safely lowered with statin drugs and BP-lowering drugs, reducing major cardiovascular (CV) events by 20%-30% within 5 years in high-risk individuals. However, there are limited data in lower-risk populations. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial is evaluating whether cholesterol lowering with a statin drug, BP lowering with low doses of 2 antihypertensive agents, and their combination safely reduce major CV events in individuals at intermediate risk who have had no previous vascular events and have average cholesterol and BP levels.METHODS:A total of 12,705 women 65 years or older and men 55 years or older with at least 1 CV risk factor, no known CV disease, and without any clear indication or contraindication to the study drugs were randomized to rosuvastatin 10 mg/d or placebo and to candesartan/hydrochlorothiazide 16/12.5 mg/d or placebo (2 × 2 factorial design) and will be followed for a mean of 5.8 years. The coprimary study outcomes are the composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke and the composite of CV death, nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, heart failure, and arterial revascularization.RESULTS:Participants were recruited from 21 countries in North America, South America, Europe, Asia, and Australia. Mean age at randomization was 66 years and 46% were women.CONCLUSIONS:The HOPE-3 trial will provide new information on cholesterol and BP lowering in intermediate-risk populations with average cholesterol and BP levels and is expected to inform approaches to primary prevention worldwide (HOPE-3 ClinicalTrials.govNCT00468923).

Variation in the Presence of Anti-Batrachochytrium dendrobatidis Bacteria of Amphibians Across Life Stages and Elevations in Ecuador.

Amphibian populations are decreasing worldwide due to a variety of factors. In South America, the chytrid fungus Batrachochytrium dendrobatidis (Bd) is linked to many population declines. The pathogenic effect of Bd on amphibians can be inhibited by specific bacteria present on host skin. This symbiotic association allows some amphibians to resist the development of the disease chytridiomycosis. Here, we aimed (1) to determine for the first time if specific anti-Bd bacteria are present on amphibians in the Andes of Ecuador, (2) to monitor anti-Bd bacteria across developmental stages in a focal amphibian, the Andean marsupial tree frog, Gastrotheca riobambae, that deposits larvae in aquatic habitats, and (3) to compare the Bd presence associated with host assemblages including 10 species at sites ranging in biogeography from Amazonian rainforest (450 masl) to Andes montane rainforest (3200 masl). We sampled and identified skin-associated bacteria of frogs in the field using swabs and a novel methodology of aerobic counting plates, and a combination of morphological, biochemical, and molecular identification techniques. The following anti-Bd bacteria were identified and found to be shared among several hosts at high-elevation sites where Bd was present at a prevalence of 32.5%: Janthinobacterium lividum, Pseudomonas fluorescens, and Serratia sp. Bd were detected in Gastrotheca spp. and not detected in the lowlands (sites below 1000 masl). In G. riobambae, recognized Bd-resistant bacteria start to be present at the metamorphic stage. Overall bacterial abundance was significantly higher post-metamorphosis and on species sampled at lower elevations. Further metagenomic studies are needed to evaluate the roles of host identity, life-history stage, and biogeography of the microbiota and their function in disease resistance.

Glucose levels are associated with cardiovascular disease and death in an international cohort of normal glycaemic and dysglycaemic men and women: the EpiDREAM cohort study.

AIMS: In an international prospective cohort study we assessed the relationship between glucose levels and incident cardiovascular events and death. METHODS AND RESULTS: 18,990 men and women were screened for entry into the DREAM clinical trial from 21 different countries. All had clinical and biochemical information collected at baseline, including an oral glucose tolerance test (OGTT), and were prospectively followed over a median (IQR) of 3.5 (3.0-4.0) years for incident cardiovascular (CV) events including coronary artery disease (CAD), stroke, congestive heart failure (CHF) requiring hospitalization, and death. After OGTT screening, 8000 subjects were classified as normoglycaemic, 8427 had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 2563 subjects had newly diagnosed type 2 diabetes mellitus (DM). There were incident events in 491 individuals: 282 CAD, 54 strokes, 19 CHF, and 164 died. The annualized CV or death event rate was 0.79/100 person-years in the overall cohort, 0.51/100 person-years in normoglycaemics, 0.92/100 person-years among subjects with IFG and/or IGT at baseline, and 1.27/100 person-years among those with DM (p for trend <0.0001). Among all subjects, a 1 mmol/l increase in fasting plasma glucose (FPG) or a 2.52 mmol/l increase in the 2-h post-OGTT glucose was associated with a hazard ratio increase in the risk of CV events or death of 1.17 (95% CI 1.13-1.22). CONCLUSIONS: In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.

Glucose levels are associated with cardiovascular disease and death in an international cohort of normal glycaemic and dysglycaemic men and women: the EpiDREAM cohort study

AIMS: In an international prospective cohort study we assessed the relationship between glucose levels and incident cardiovascular events and death.METHODS AND RESULTS: 18,990 men and women were screened for entry into the DREAM clinical trial from 21 different countries. All had clinical and biochemical information collected at baseline, including an oral glucose tolerance test (OGTT), and were prospectively followed over a median (IQR) of 3.5 (3.0-4.0) years for incident cardiovascular (CV) events including coronary artery disease (CAD), stroke, congestive heart failure (CHF) requiring hospitalization, and death. After OGTT screening, 8000 subjects were classified as normoglycaemic, 8427 had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 2563 subjects had newly diagnosed type 2 diabetes mellitus (DM). There were incident events in 491 individuals: 282 CAD, 54 strokes, 19 CHF, and 164 died. The annualized CV or death event rate was 0.79/100 person-years in the overall cohort, 0.51/100 person-years in normoglycaemics, 0.92/100 person-years among subjects with IFG and/or IGT at baseline, and 1.27/100 person-years among those with DM (p for trend <0.0001). Among all subjects, a 1 mmol/l increase in fasting plasma glucose (FPG) or a 2.52 mmol/l increase in the 2-h post-OGTT glucose was associated with a hazard ratio increase in the risk of CV events or death of 1.17 (95% CI 1.13-1.22).CONCLUSIONS: In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.

Long-term effect of rosiglitazone and/or ramipril on the incidence of diabetes: DREAM On (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication Ongoing Follow-up) Investigators

AIMS/HYPOTHESIS: The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial reported that 3 years of therapy with rosiglitazone reduced the primary outcome of diabetes or death by 60%. Here we investigated whether an effect on diabetes prevention persists more than 1.5 years after therapy has been discontinued. METHODS: The DREAM On passive follow-up study was conducted at 49 of the 191 DREAM sites. Consenting participants were invited to have a repeat OGTT 1-2 years after active therapy ended. A diagnosis of diabetes at that time was based on either a fasting or 2 h plasma glucose level of ¡Ý7.0 mmol/l or ¡Ý11.1 mmol/l, respectively, or a confirmed diagnosis by a non-study physician. Regression to normoglycaemia was defined as a fasting and 2 h plasma glucose level of <6.1 mmol/l and <7.8 mmol/l, respectively. RESULTS: After a median of 1.6 years after the end of the trial and 4.3 years after randomisation, rosiglitazone participants had a 39% lower incidence of the primary outcome (hazard ratio [HR] 0.61, 95% CI 0.53-0.70; p < 0.0001) and 17% more regression to normoglycaemia (95% CI 1.01-1.34; p = 0.034). When the analysis was restricted to the passive follow-up period, a similar incidence of both the primary outcome and regression was observed in people from both treatment groups (HR 1.00, 95% CI 0.81-1.24 and HR 1.14, 95% CI 0.97-1.32, respectively). Similar effects were noted when new diabetes was analysed separately from death. Ramipril did not have any significant long-term effect. CONCLUSIONS/INTERPRETATION: Time-limited exposure to rosiglitazone reduces the longer term incidence of diabetes by delaying but not reversing the underlying disease process.

Source analysis of alpha rhythm reactivity using LORETA imaging with 64-channel EEG and individual MRI.

Conventional EEG and quantitative EEG visual stimuli (close-open eyes) reactivity analysis have shown their usefulness in clinical practice; however studies at the level of EEG generators are limited. The focus of the study was visual reactivity of cortical resources in healthy subjects and in a stroke patient. The 64 channel EEG and T1 magnetic resonance imaging (MRI) studies were obtained from 32 healthy subjects and a middle cerebral artery stroke patient. Low Resolution Electromagnetic Tomography (LORETA) was used to estimate EEG sources for both close eyes (CE) vs. open eyes (OE) conditions using individual MRI. The t-test was performed between source spectra of the two conditions. Thresholds for statistically significant t values were estimated by the local false discovery rate (lfdr) method. The Z transform was used to quantify the differences in cortical reactivity between the patient and healthy subjects. Closed-open eyes alpha reactivity sources were found mainly in posterior regions (occipito-parietal zones), extended in some cases to anterior and thalamic regions. Significant cortical reactivity sources were found in frequencies different from alpha (lower t-values). Significant changes at EEG reactivity sources were evident in the damaged brain hemisphere. Reactivity changes were also found in the "healthy" hemisphere when compared with the normal population. In conclusion, our study of brain sources of EEG alpha reactivity provides information that is not evident in the usual topographic analysis.

Recognizing a mother's voice in the persistent vegetative state.

We studied an 8-year-old boy after a near-drowning left him in a vegetative state (VS) for 4 years before the study. Findings fulfilled all clinical criteria for the diagnosis of VS. The purpose of this study was to investigate whether there was significant differential activation of the brain in response to hearing his mother's voice compared with the voices of unknown women. The data were assessed using quantitative electric tomography (QEEGt), a technique that combines anatomical information of the brain by MRI with EEG patterns to estimate the sources of the EEG within the brain. We found significant differences for EEG frequencies from 14-58 Hz, with a peak at 33.2 Hz (gamma band). The 3D reconstruction showed that these statistical differences were localized in the lateral and posterior regions of the left hemisphere. No significant differences were found between unknown women vs. basal conditions. These results demonstrate recognition of the mother's voice and indicate high-level residual linguistic processing in a patient meeting clinical criteria for VS. These findings launch new ethical and practical implications for the management of VS patients.

The effect of 6-monthly application of 40% chlorhexidine varnish on the microflora and dental caries incidence in a population of children in Surinam.

This study is aimed at determining whether a commercially available varnish, containing 40% chlorhexidine, is able to reduce the numbers of mutans streptococci and lactobacilli in saliva, in a moderately caries-active population in Surinam. 238 children, ages 13-14 years, were selected from different schools in Paramaribo, Surinam. From these children, total dental status was recorded and saliva samples were taken. At baseline and every 6 months, a 40% chlorhexidine varnish (EC40) was applied. The control group received a neutral gel that did not contain chlorhexidine. The numbers of salivary mutans streptococci and lactobacilli were calculated by standard methods, and the caries status was recorded every 12 months. The study lasted 30 months. The results indicate that chlorhexidine varnish did not decrease the numbers of cariogenic bacteria, nor did it decrease caries progression. Moreover, in this population with a low dental health care, children with lactobacilli present in the saliva above our detection level, the chlorhexidine varnish even tended to increase caries progression, possibly due to selection of aciduric and acidogenic oral bacterial species. We therefore conclude that 40% chlorhexidine varnish is not likely to decrease caries in children in a high-treatment-need population without treatment of the sources of infection.

EEG changes during word and figure categorization.

OBJECTIVE: To analyze whether the EEG changes observed during figure and word categorization are compatible with either the dual, the common amodal, or the alternative model (modality-specific codes for words and pictures, where meaning is represented for both in a higher-order amodal system) for semantic knowledge. METHODS: EEG was recorded during word and figure categorization of animals or non-animals in a group of 28 children 8-10 years old. Computation of EEG sources in the frequency domain using variable resolution electrical tomography (VARETA) and their statistical evaluation by statistical parametric mapping were carried out. RESULTS: At all frequencies, there were significant changes between EEG segments prior to the presentation of the stimuli and EEG segments recorded after the stimuli. Post-segments showed more power from 1.56 to 7.02 Hz, and less power than pre-segments from 8 to 12.48 Hz. EEG changes were only observed in the word task at: 3.9 (left occipital), 4.68, 5.46, and 6.24 Hz (temporo-occipital regions). These changes may be associated with visual encoding of words. Frequencies 7.8 and 17.94 Hz increased in prefrontal, anterior cingulate, and anterior temporal regions only during figure categorization. The prefrontal region may be related to object working memory. Thus, these frequencies might be related to figure codification. No significant differences between tasks were observed at 3.12 and 7.02 Hz in very wide brain areas (all lobes except occipital), suggesting that the amodal semantic system storage could be the model compatible with figure and word categorization. CONCLUSIONS: Thus, our results support the modified amodal semantic hypothesis, which advocates that the meanings of both kinds of stimuli are represented in a conceptual memory that receives input from the logogen and iconogen systems.

Sources of abnormal EEG activity in brain infarctions.

EEGs from 16 patients with stroke in three different stages of evolution were recorded. EEG sources were calculated every 0.39 Hz by frequency domain VARETA. The main source was within the delta band in 2 out of 4 chronic patients, and in 67% of the patients in the acute or subacute stages when edema (cytotoxic or vasogenic) was present. Moreover, all patients showed abnormal activity in the theta band. Sources of abnormal activity in cortical or corticosubcortical infarcts were located in the cortex, surrounding the lesion. At the site of the infarct, a decrease of EEG power was observed. Sources of abnormal theta power coincided with edema and/or ischemic penumbra.

The sixth Carlos E. Rubio Memorial Lecture. Prevention and treatment of variceal hemorrhage.

The medical treatment of portal hypertension has experienced a marked progress in the past decade due to the introduction of effective portal hypotensive therapy. This has been possible because of the better understanding of the pathophysiological mechanisms leading to portal hypertension. A major step forward was the introduction of beta-blockers for the prevention of bleeding and rebleeding from gastroesophageal varices. Effective therapy requires the reduction of the hepatic venous pressure gradient (HVPG) to 12 mmHg or below, or at least by 20% of baseline values. Unfortunately, this is only achieved in 1/3 to 1/2 of patients. Combination therapy, associating isosorbide-5-mononitrate and propranolol or nadolol administration enhances the reduction in portal pressure and increases the number of patients in whom HVPG decreases by more than 20% of baseline values and below 12 mmHg. Randomized clinical trials (RCT's) do support the concept that combination therapy is more effective than propranolol or nadolol alone, significantly better than sclerotherapy, and probably than endoscopic banding ligation. Therapy may be complemented by the association of spironolactone. The main inconvenience of pharmacological therapy is that there is no non-invasive method available to detect non-responders to treatment. Failures of drug therapy should be managed endoscopically. Failures of endoscopic treatment require 'rescue' by means of TIPS or shunt surgery. Patients with advanced liver failure should be considered for orthotopic liver transplantation, and put into a waiting list if eligible. In the treatment of acute variceal bleeding pharmacological therapy offer the unique advantage of allowing to provide specific therapy immediately after arrival to hospital, or even during transferral to hospital by ambulance, since it does not require sophisticated equipment and highly qualified medical staff. Vasopressin has been abandoned because of its toxicity, although this can be reduced by the combined administration of transdermal nitroglycerin. Terlipressin has longer effects and is more effective and safer than vasopressin alone or in combination with nitroglycerin. It has proved to be effective and to decrease mortality from bleeding in double-blind studies. RCT's have shown that this drug is as effective and safer than emergency sclerotherapy. Therapy should be maintained for five days to prevent early rebleeding. Somatostatin is probably as effective as terlipressin. Octreotide is probably useful after endoscopic therapy but can not be recommended as first line treatment. Endoscopic injection sclerotherapy and endoscopic banding ligation are very effective, but require well trained medical staff. There is an increasing trend for initiating therapy with a pharmacological agent, followed by semi-emergency endoscopic therapy as soon as a well trained endoscopist is available (within 12-24 hours), while maintaining drug therapy for 5 days. Failures of medical therapy may be treated by a second session of endoscopic treatment, but if this fails TIPS of emergency surgery should be done. In high-risk situations, such as bleeding from gastric varices or in patients with advanced liver failure, the decision for TIPS or surgery should be done earlier, after failure of the initial treatment.

Do specific EEG frequencies indicate different processes during mental calculation?

EEG recordings during mental calculation and a control task (with presentation of stimuli with similar physical characteristics to the arithmetic symbols) were obtained in 10 subjects. Narrow band analyses of the EEG and distributed sources for each EEG frequency were calculated using variable resolution electromagnetic tomography. Significant differences between the sources for arithmetic and control tasks were observed at 3.9 Hz within Broca's and left parietotemporal cortices, suggesting that this frequency may be related with the production of internal speech, storage and rehearsal of verbal working memory. Differences at 5.46 Hz within the right dorsolateral prefrontal cortex were considered to be associated to sustained attention. The decrease at 12.46 Hz within the left parietal cortex was interpreted as a sign of retrieval of arithmetic facts from long term memory.

[A patient with generalized actinomycosis]. / Een patiënt met een gegeneraliseerde actinomycose.

A 36-year-old man was admitted because of haemoptysis and weight loss. Despite elaborate investigations, including multiple biopsies of affected organs (pleura, lung, kidney and liver) no diagnosis was established. The patient refused further diagnostic procedures and left hospital for winti treatment in Surinam. He did not take the prescribed pheneticillin and returned after seven weeks in a very poor condition. The second admission was complicated by septic shock. Despite intensive treatment he died. On autopsy actinomycosis abscesses were found in lung, liver and kidney. Even when suspected, an infection with Actinomyces is difficult to diagnose. Without adequate treatment this infection can lead to life-threatening complications.

High resolution quantitative EEG analysis.

High resolution spectral methods are explored as an alternative to broad band spectral parameters (BBSP) in quantitative EEG analysis. In a previous paper (Valdes et al. 1990b) regression equations ("Developmental surfaces") were introduced to characterize the age-frequency distribution of the mean and standard deviation of the log spectral EEG power in a normative sample. These normative surfaces allow the calculation of z transformed spectra for all derivations of the 10/20 system and z maps for each frequency. Clinical material is presented that illustrates how these procedures may pinpoint frequencies of abnormal brain activity and their topographic distribution, avoiding the frequency and spatial "smearing" that may occur using BBSP. The increased diagnostic accuracy of high resolution spectral methods is demonstrated by means of receiver operator characteristic (ROC) curve analysis. Procedures are introduced to avoid type I error inflation due to the use of more variables in this type of procedure.

La cirugía estático funcional del colesteatoma / Static functional surgery of cholesteotoma

El gran porcentaje de fracasos en la cirugía del colesteatoma (recurrente y residual) a largo plazo, tanto con las técnicas abiertas, como con las técnicas cerradas y asimismo los bajos índices de resultados funcionales socialmente útiles, han sido motivo de reflexión para la mayoría de los autores, sobre el tipo de técnica quirúrgica más adecuada para mejorar los resultados estático-funcionales. De un total de 337 casos de colesteatoma intervenido en un período de cinco años (1982-1987) con un seguimiento medio post-operatorio de 3.8 años. 19 casos (5.6 por ciento) corresponden a niños menores de 10 años y 39 (11.5 por ciento) a mayores de 60 años. La localización del colesteatoma era mayoritaria en ático y antro (79 por ciento) con extensión a mastoides en un 52 por ciento y dos casos de colesteatoma congénito con tímpano íntegro. El 98% de los pacientes presentaban alteraciones de la cadena osicular. En un 5.6 por ciento (19) se realizó una mastoidectomía radical, en 234 (69 por ciento) una mastoidectomía o aticoantrotomía con timpanoplastía y reconstrucción del defecto óseo de la pared posterior del conducto y en un 25 por ciento de casos (84 oídos) una técnica cerrada con conservación de la pared posterior y reconstrucción timpanosicular. A los 3.8 años, los fracasos patológicos (colesteatoma residual y colesteatoma recidivante) fueron del 18 por ciento (10 por ciento con las técnicas abiertas, 14 por ciento con las técnicas reconstructivas y el 31 por ciento con las técnicas cerradas) y un 40 por ciento de resultados auditivos socialmente útiles con un Rinne de O-20 dB (56 por ciento en los casos con estribo móvil y 24 por ciento sin supraestructura estapedial). En la actualidad, la técnica más aplicada en la cirugía del colesteatoma es la radical modificada con reconstrucción timpánica.

Estapedectomía versus estapedotomía: análisis de los resultados a largo plazo / Stapedectomy versus stapedotomy: analysis of the results at long-term

Se analizan resultados de la estapedectomía y la estapedotomía de un total de 4125 operados entre 1965 a 1985. Los mejores resultados en cuanto al "sobre-cierre" de la brecha aérea-ósea se registraron en aquellos pacientes con platinectomía total (87%). En el resto de los resultados no hubo diferencias significativas. En el caso de la otoesclerosis obliterante, la estapedectomía y el fresaje discreto de la lesión sobre la ventana oval, presenta mayor ventaja y mejora los resultados auditivos. El tratamiento con fluoruro de sódio (NaF) aminora y detiene el progresivo deterioro neurosensorial auditivo y tiene un futuro prometedor