Novel compounds that enhance Agrobacterium-mediated plant transformation by mitigating oxidative stress.

KEY MESSAGE: Agrobacterium tumefaciens caused tissue browning leading to subsequent cell death in plant transformation and novel anti-oxidative compounds enhanced Agrobacterium -mediated plant transformation by mitigating oxidative stress. Browning and death of cells transformed with Agrobacterium tumefaciens is a long-standing and high impact problem in plant transformation and the agricultural biotechnology industry, severely limiting the production of transgenic plants. Using our tomato cv. MicroTom transformation system, we demonstrated that Agrobacterium caused tissue browning (TB) leading to subsequent cell death by our correlation study. Without an antioxidant (lipoic acid, LA) TB was severe and associated with high levels of GUS transient expression and low stable transformation frequency (STF). LA addition shifted the curve in that most TB was intermediate and associated with the highest levels of GUS transient expression and STF. We evaluated 18 novel anti-oxidative compounds for their potential to enhance Agrobacterium-mediated transformation, by screening for TB reduction and monitoring GUS transient expression. Promising compounds were further evaluated for their effect on MicroTom and soybean STF. Among twelve non-antioxidant compounds, seven and five significantly (P < 0.05) reduced TB and increased STF, respectively. Among six antioxidants four of them significantly reduced TB and five of them significantly increased STF. The most efficient compound found to increase STF was melatonin (MEL, an antioxidant). Optimal concentrations and stages to use MEL in transformation were determined, and Southern blot analysis showed that T-DNA integration was not affected by MEL. The ability of diverse compounds with different anti-oxidative mechanisms can reduce Agrobacterium-mediated TB and increase STF, strongly supporting that oxidative stress is an important limiting factor in Agrobacterium-mediated transformation and the limiting factor can be controlled by these compounds at different levels.

Auditory brainstem and middle latency responses recorded at fast rates with randomized stimulation.

Randomized stimulation and averaging (RSA) allows auditory evoked potentials (AEPs) to be recorded at high stimulation rates. This method does not perform deconvolution and must therefore deal with interference derived from overlapping transient evoked responses. This paper analyzes the effects of this interference on auditory brainstem responses (ABRs) and middle latency responses (MLRs) recorded at rates of up to 300 and 125 Hz, respectively, with randomized stimulation sequences of a jitter both greater and shorter than the dominant period of the ABR/MLR components. Additionally, this paper presents an advanced approach for RSA [iterative-randomized stimulation and averaging (I-RSA)], which includes the removal of the interference associated with overlapping responses through an iterative process in the time domain. Experimental results show that (a) RSA can be efficiently used in the recording of AEPs when the jitter of the stimulation sequence is greater than the dominant period of the AEP components, and (b) I-RSA maintains all the advantages of RSA and is not constrained by the restriction of a minimum jitter. The significance of the results of this study is discussed.

A flexible and inexpensive high-performance auditory evoked response recording system appropriate for research purposes.

Recording auditory evoked responses (AER) is done not only in hospitals and clinics worldwide to detect hearing impairments and estimate hearing thresholds, but also in research centers to understand and model the mechanisms involved in the process of hearing. This paper describes a high-performance, flexible, and inexpensive AER recording system. A full description of the hardware and software modules that compose the AER recording system is provided. The performance of this system was evaluated by conducting five experiments with both real and artificially synthesized auditory brainstem response and middle latency response signals at different intensity levels and stimulation rates. The results indicate that the flexibility of the described system is appropriate to record AER signals under several recording conditions. The AER recording system described in this article is a flexible and inexpensive high-performance AER recording system. This recording system also incorporates a platform through which users are allowed to implement advanced signal processing methods. Moreover, its manufacturing cost is significantly lower than that of other commercially available alternatives. These advantages may prove useful in many research applications in audiology.

Recombinant cellulase accumulation in the leaves of mature, vegetatively propagated transgenic sugarcane.

The cost of enzymes that hydrolyse lignocellulosic substrates to fermentable sugars needs to be reduced to make cellulosic ethanol a cost-competitive liquid transport fuel. Sugarcane is a perennial crop and the successful integration of cellulase transgenes into the sugarcane production system requires that transgene expression is stable in the ratoon. Herein, we compared the accumulation of recombinant fungal cellobiohydrolase I (CBH I), fungal cellobiohydrolase II (CBH II), and bacterial endoglucanase (EG) in the leaves of mature, initial transgenic sugarcane plants and their mature ratoon. Mature ratoon events containing equivalent or elevated levels of active CBH I, CBH II, and EG in the leaves were identified. Further, we have demonstrated that recombinant fungal CBH I and CBH II can resist proteolysis during sugarcane leaf senescence, while bacterial EG cannot. These results demonstrate the stability of cellulase enzyme transgene expression in transgenic sugarcane and the utility of sugarcane as a biofactory crop for production of cellulases.

Automatic quality assessment and peak identification of auditory brainstem responses with fitted parametric peaks.

The recording of the auditory brainstem response (ABR) is used worldwide for hearing screening purposes. In this process, a precise estimation of the most relevant components is essential for an accurate interpretation of these signals. This evaluation is usually carried out subjectively by an audiologist. However, the use of automatic methods for this purpose is being encouraged nowadays in order to reduce human evaluation biases and ensure uniformity among test conditions, patients, and screening personnel. This article describes a new method that performs automatic quality assessment and identification of the peaks, the fitted parametric peaks (FPP). This method is based on the use of synthesized peaks that are adjusted to the ABR response. The FPP is validated, on one hand, by an analysis of amplitudes and latencies measured manually by an audiologist and automatically by the FPP method in ABR signals recorded at different stimulation rates; and on the other hand, contrasting the performance of the FPP method with the automatic evaluation techniques based on the correlation coefficient, FSP, and cross correlation with a predefined template waveform by comparing the automatic evaluations of the quality of these methods with subjective evaluations provided by five experienced evaluators on a set of ABR signals of different quality. The results of this study suggest (a) that the FPP method can be used to provide an accurate parameterization of the peaks in terms of amplitude, latency, and width, and (b) that the FPP remains as the method that best approaches the averaged subjective quality evaluation, as well as provides the best results in terms of sensitivity and specificity in ABR signals validation. The significance of these findings and the clinical value of the FPP method are highlighted on this paper.

Improved molecular tools for sugar cane biotechnology.

Sugar cane is a major source of food and fuel worldwide. Biotechnology has the potential to improve economically-important traits in sugar cane as well as diversify sugar cane beyond traditional applications such as sucrose production. High levels of transgene expression are key to the success of improving crops through biotechnology. Here we describe new molecular tools that both expand and improve gene expression capabilities in sugar cane. We have identified promoters that can be used to drive high levels of gene expression in the leaf and stem of transgenic sugar cane. One of these promoters, derived from the Cestrum yellow leaf curling virus, drives levels of constitutive transgene expression that are significantly higher than those achieved by the historical benchmark maize polyubiquitin-1 (Zm-Ubi1) promoter. A second promoter, the maize phosphonenolpyruvate carboxylate promoter, was found to be a strong, leaf-preferred promoter that enables levels of expression comparable to Zm-Ubi1 in this organ. Transgene expression was increased approximately 50-fold by gene modification, which included optimising the codon usage of the coding sequence to better suit sugar cane. We also describe a novel dual transcriptional enhancer that increased gene expression from different promoters, boosting expression from Zm-Ubi1 over eightfold. These molecular tools will be extremely valuable for the improvement of sugar cane through biotechnology.

An improved chemically inducible gene switch that functions in the monocotyledonous plant sugar cane.

Chemically inducible gene switches can provide precise control over gene expression, enabling more specific analyses of gene function and expanding the plant biotechnology toolkit beyond traditional constitutive expression systems. The alc gene expression system is one of the most promising chemically inducible gene switches in plants because of its potential in both fundamental research and commercial biotechnology applications. However, there are no published reports demonstrating that this versatile gene switch is functional in transgenic monocotyledonous plants, which include some of the most important agricultural crops. We found that the original alc gene switch was ineffective in the monocotyledonous plant sugar cane, and describe a modified alc system that is functional in this globally significant crop. A promoter consisting of tandem copies of the ethanol receptor inverted repeat binding site, in combination with a minimal promoter sequence, was sufficient to give enhanced sensitivity and significantly higher levels of ethanol inducible gene expression. A longer CaMV 35S minimal promoter than was used in the original alc gene switch also substantially improved ethanol inducibility. Treating the roots with ethanol effectively induced the modified alc system in sugar cane leaves and stem, while an aerial spray was relatively ineffective. The extension of this chemically inducible gene expression system to sugar cane opens the door to new opportunities for basic research and crop biotechnology.

A study of adaptation mechanisms based on ABR recorded at high stimulation rate.

OBJECTIVE: This paper analyzes the fast and slow mechanisms of adaptation through a study of latencies and amplitudes on ABR recorded at high stimulation rates using the randomized stimulation and averaging (RSA) technique. METHODS: The RSA technique allows a separate processing of auditory responses, and is used, in this study, to categorize responses according to the interstimulus interval (ISI) of their preceding stimulus. The fast and slow mechanisms of adaptation are analyzed by the separated responses methodology, whose underlying principles and mathematical basis are described in detail. RESULTS: The morphology of the ABR is influenced by both fast and slow mechanisms of adaptation. These results are consistent with previous animal studies based on spike rate. CONCLUSIONS: Both fast and slow mechanisms of adaptation are present in all subjects. In addition, the distribution of the jitter and the sequencing of the stimuli may be critical parameters when obtaining reliable ABRs. SIGNIFICANCE: The separated responses methodology enables for the first time the analysis of the fast and slow mechanisms of adaptation in ABR obtained at stimulation rates greater than 100 Hz. The non-invasive nature of this methodology is appropriate for its use in humans.

Analysis of electrical thresholds and maximum comfortable levels in cochlear implant patients.

OBJECTIVE: It is well known that a proper fitting of the cochlear implant processor is relevant to provide good quality in speech perception. The aim of this study is to extract statistical information to be applied for fitting the processor. METHODS: This study is based on the programming maps of 121 patients, aged from 18 months to 68 years at the moment of implantation. All subjects were implanted with the COMBI 40+ cochlear implant at San Cecilio University Hospital, Granada (Spain). The patients were classified into groups based on their age at implantation: younger than 5 years, between 5 and 16 years, and older than 16 years. The patients in each age-based group were divided into two subgroups, considering whether they had recent hearing experience or not. A special group including patients affected by severe damages in the cochlea was also defined. RESULTS: Relationships between the programming parameters and factors like the age at implantation, the hearing experience and the presence of severe cochlear damage were found. The THR levels for patients younger than 5 years were significantly lower than those for patients implanted between 5 and 16 years, and this group presented significantly lower THR levels than adults. The MCL levels were not significantly influenced by the age at implantation. A significant increment was observed for both, MCL and THR levels, when patients were affected by severe cochlear damage. A significant increment in the THR levels were observed for patients with no recent hearing experience, while no significant differences were found for MCL levels. This study also analyzes the distribution along the cochlea of the stimulation levels. In the case of patients not affected by severe cochlear damage, the most basal electrodes presented a significant increment in the stimulation levels with respect to the rest of electrodes. CONCLUSION: This work provides information of great value for programming the speech processors, particularly when the subjective responses of the patients are not sufficient. The application in our ENT Service has reduced substantially the average time needed to obtain an acceptable fitting of the processor, especially in children. Our study also shows that electrical thresholds are a good indicator of the functionality of the auditory nerve. The analysis of this parameter highlights the importance of an early intervention as well as a deep insertion of the electrode carrier in order to obtain the maximum functionality from the cochlear implant.

Long-term evolution of the electrical stimulation levels for cochlear implant patients.

OBJECTIVES: The stimulation levels programmed in cochlear implant systems are affected by an evolution since the first switch-on of the processor. This study was designed to evaluate the changes in stimulation levels over time and the relationship between post-implantation physiological changes and with the hearing experience provided by the continuous use of the cochlear implant. METHODS: Sixty-two patients, ranging in age from 4 to 68 years at the moment of implantation participated in this study. All subjects were implanted with the 12 channels COMBI 40+ cochlear implant at San Cecilio University Hospital, Granada, Spain. Hearing loss etiology and progression characteristics varied across subjects. RESULTS: The analyzed programming maps show that the stimulation levels suffer a fast evolution during the first weeks after the first switch-on of the processor. Then, the evolution becomes slower and the programming parameters tend to be stable at about 6 months after the first switch-on. The evolution of the stimulation levels implies an increment of the electrical dynamic range, which is increased from 15.4 to 20.7 dB and improves the intensity resolution. A significant increment of the sensitivity to acoustic stimuli is also observed. For some patients, we have also observed transitory changes in the electrode impedances associated to secretory otitis media, which cause important changes in the programming maps. CONCLUSION: We have studied the long-term evolution of the stimulation levels in cochlear implant patients. Our results show the importance of systematic measurements of the electrode impedances before the revision of the programming map. This report also highlights that the evolution of the programming maps is an important factor to be considered in order to determine an adequate calendar fitting of the cochlear implant processor.

Recording of auditory brainstem response at high stimulation rates using randomized stimulation and averaging.

The recording of auditory brainstem response (ABR) at high stimulation rates is of great interest in audiology. It allows a more accurate diagnosis of certain pathologies at an early stage and the study of different mechanisms of adaptation. This paper proposes a methodology, which we will refer to as randomized stimulation and averaging (RSA) that allows the recording of ABR at high stimulation rates using jittered stimuli. The proposed method has been compared with quasi-periodic sequence deconvolution (QSD) and conventional (CONV) stimulation methodologies. Experimental results show that RSA provides a quality in ABR recordings similar to that of QSD and CONV. Compared with CONV, RSA presents the advantage of being able to record ABR at rates higher than 100 Hz. Compared with QSD, the formulation of RSA is simpler and allows more flexibility on the design of the pseudorandom sequence. The feasibility of the RSA methodology is validated by an analysis of the morphology, amplitudes, and latencies of the most important waves in ABR recorded at high stimulation rates from eight normal hearing subjects.

Auditory maturity and hearing performance in inner ear malformations: a histological and electrical stimulation approach.

The objective of this study was to assess the auditory performance of the neural structures in response to controlled electrical stimulation period. A prospective cohort study focused on the intracochlear electrical stimulation parameters and hearing performance of patients suffering different cochlear malformations who were treated by cochlear implants constituted the study design. The study sample constituted 16 patients, suffering profound prelingual hearing impairment, diagnosed on the basis of radiological criteria as having an inner ear malformation, and who underwent cochlear implantation and were followed for 24 months. Patients with common cavities, characterized by fewer nerve structures involved, less epithelial penetration, and deficient cochlear tonotopy distribution showed have higher thresholds and electrical charges than patients with cochlear hypoplasia, who in turn have higher thresholds than patients with minor malformations (p < 0.05). Furthermore, word perception was severely compromised in patients with a common cavity malformation and was also poor in patients with cochlear hypoplasia, who were unable to discriminate more than 50% of the words and relied on visual cues as a necessary aid to communication. Better results were reached by minor malformed inner ears. To conclude, the number of nerve structures involved, epithelial penetration and deficient cochlear tonotopy are responsible of inner ear functionality.

Assessment of the subjective benefit of electric acoustic stimulation with the abbreviated profile of hearing aid benefit.

CONCLUSION: This study demonstrates that electric-acoustic stimulation (EAS) significantly decreases the subjective impairment in speech perception. OBJECTIVES: To assess the subjective benefit of EAS over the first 12 months after EAS fitting using the Abbreviated Profile of Hearing Aid Benefit (APHAB). METHOD: Twenty-three EAS users, implanted with either the PULSAR(CI)(100) FLEX(EAS) provided with the DUET EAS processor or the COMBI40+ Medium provided with the TEMPO+ speech processor, were included. Electric stimulation was activated about 1 month postoperatively; ipsilateral acoustic stimulation was added 2 months thereafter. EAS benefit was measured preoperatively with only a hearing aid and postoperatively at EAS fitting and then 3, 6 and 12 months after EAS fitting using the APHAB. RESULTS: Subjects reported significant improvements in the global score with a mean decrease in impairment from 74% preoperatively to 45% after 3 months of EAS use. Furthermore, clinical relevance was demonstrated in multiple subscales between preoperative and first fitting reflecting a true benefit of EAS with a probability of 95%.

Accumulation of recombinant cellobiohydrolase and endoglucanase in the leaves of mature transgenic sugar cane.

A major strategic goal in making ethanol from lignocellulosic biomass a cost-competitive liquid transport fuel is to reduce the cost of production of cellulolytic enzymes that hydrolyse lignocellulosic substrates to fermentable sugars. Current production systems for these enzymes, namely microbes, are not economic. One way to substantially reduce production costs is to express cellulolytic enzymes in plants at levels that are high enough to hydrolyse lignocellulosic biomass. Sugar cane fibre (bagasse) is the most promising lignocellulosic feedstock for conversion to ethanol in the tropics and subtropics. Cellulolytic enzyme production in sugar cane will have a substantial impact on the economics of lignocellulosic ethanol production from bagasse. We therefore generated transgenic sugar cane accumulating three cellulolytic enzymes, fungal cellobiohydrolase I (CBH I), CBH II and bacterial endoglucanase (EG), in leaves using the maize PepC promoter as an alternative to maize Ubi1 for controlling transgene expression. Different subcellular targeting signals were shown to have a substantial impact on the accumulation of these enzymes; the CBHs and EG accumulated to higher levels when fused to a vacuolar-sorting determinant than to an endoplasmic reticulum-retention signal, while EG was produced in the largest amounts when fused to a chloroplast-targeting signal. These results are the first demonstration of the expression and accumulation of recombinant CBH I, CBH II and EG in sugar cane and represent a significant first step towards the optimization of cellulolytic enzyme expression in sugar cane for the economic production of lignocellulosic ethanol.

Using evoked compound action potentials to assess activation of electrodes and predict C-levels in the Tempo+ cochlear implant speech processor.

OBJECTIVE: In this study, we analyze how electrically evoked compound action potential (ECAP) responses can be used to assess whether electrodes should be activated in the map and to estimate C levels in the Med-El Tempo+ Cochlear Implant Speech Processor. DESIGN: ECAP thresholds were measured using the ECAP Recording System of the Pulsar CI implant. Twenty-one postlingually and 28 prelingually deafened patients participated in this study. The relationship between ECAP responses and the activation of electrodes was analyzed. Because an error in the estimation of T levels (behavioral thresholds) has less effect on hearing quality than an error in the estimation of C levels in the Tempo+ cochlear implant speech processor (maximum comfort levels), correlation and regression analyses were performed between ECAP thresholds and C levels. RESULTS: The observation of an evoked potential generally implied that the electrode was activated because only 3.5% of electrodes that yielded measurable evoked responses were deactivated, because of collateral stimulations or an unpleasant hearing sensation. In contrast, the absence of an evoked potential did not imply that an electrode should be deactivated, because 20% of these electrodes provided a useful auditory sensation. ECAP responses did not predict the absolute behavioral comfort levels because of the excessive error between behavioral C levels and those derived from ECAP thresholds (the mean relative error is 43.78%). However, by applying a normalization procedure, ECAP measurements allowed the C-level profile to be predicted with a mean relative error of 6%; that is, they provided useful data to determine the C level of each electrode relative to the average C level of the patient. CONCLUSIONS: ECAP is a reliable and an useful objective measurement that can assist in the fitting of the Tempo+ cochlear implant speech processor. From results presented in this work, a protocol is proposed for fitting this cochlear implant system. This protocol facilitates appropriate cochlear implant fitting, particularly for children or uncooperative patients.

Reducing blanking artifact in electrically evoked compound action potentials.

The main source of distortion in the recording of the electrically evoked compound action potentials is the stimulus artifact. The popular hardware blanking technique tends to reduce this artifact, but generates a blanking artifact as a consequence of the transient state in the amplifier. In this paper we propose two techniques to deal with the blanking artifact. The proposed techniques are combined with conventional and generalized alternating stimulation in order to reduce both stimulus and blanking artifacts in the recording of the evoked potentials. A comparison over 126 evoked potential recordings reveals that the proposed blanking artifact reduction methods improve the quality of electrically evoked compound action potential recordings.

Prophylactic effect of clarithromycin in skin flap complications in cochlear implants surgery.

OBJECTIVES/HYPOTHESIS: To assess the usefulness of postoperative clarithromycin versus classical postoperative prophylaxis with occlusive dressing to prevent cochlear implant skin flap complications. STUDY DESIGN: Cohort study. METHODS: Surgical site infections were compared in four groups: 1) ceramic/classical postoperative cares (21 patients), 2) titanium-silicon/classical postoperative cares (75), 3) ceramic/clarithromycin (24), and 4) titanium-silicon/clarithromycin (76). Preoperative ceftriaxone was systematically used in all patients in all four groups. Patients were followed up for at least 4 months. Attributable risk and number needed to treat were calculated. RESULTS: All infections appeared in titanium-silicon covered implants, and the risk of surgical site infection was 8.1 times higher in patients treated only with ceftriaxone and classical postoperative prophylaxis compared to those also given clarithromycin. Eleven patients needed to receive clarithromycin to avoid surgical infection. CONCLUSIONS: Long-term treatment with low-dose clarithromycin may reduce the incidence of surgical site infections.

Complications and pitfalls of cochlear implantation in otosclerosis: a 6-year follow-up cohort study.

OBJECTIVE: To describe and discuss the midterm complications and pitfalls reported in patients with otosclerosis who received a cochlear implant. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS: Fifteen patients who received a cochlear implant for otosclerosis, followed up for a minimum of 6 years. Onset of hearing loss occurred at a mean age (+/-standard deviation [SD]) of 32.6 +/- 8.6 years. Mean duration (+/-SD) of hearing loss was 26.8 +/- 7.9 years, and mean age (+/-SD) at implant surgery was 58.7 +/- 9.5 years. INTERVENTIONS: Before cochlear implantation, hearing thresholds were tested, and temporal bone anatomy and otosclerotic lesions were documented by high-resolution computed tomography and magnetic resonance imaging. All patients were implanted with a Med-El Combi 40 + device and a Standard Electrode Array. MAIN OUTCOME MEASURES: The number of inserted electrodes was checked by x-ray. After cochlear implantation, hearing skills were tested, fitting parameters were recorded, and complications were noted. RESULTS: As the disease progressed, the number of electrodes decreased, and the electrical thresholds, maximum comfort levels, and electric charge increased; these changes were more evident in the middle electrodes. Although facial nerve stimulation rate was lower than previously reported (13.3%), it increased during follow-up. Two patients (13.3%) had untreatable tinnitus. Nevertheless, all speech discrimination parameters improved significantly in all patients. CONCLUSION: Despite the need for special fitting strategies and the appearance of complications, facial nerve stimulation, and tinnitus, improvements in speech discrimination tests support the use of cochlear implantation for patients with otosclerosis.

[Surgical options for hearing loss in patients with osteogenesis imperfecta]. / Posibilidades de tratamiento quirúrgico de la hipoacusia en pacientes afectados de osteogénesis imperfecta.

The aim of the study is to present the severe, extensive lesions in the temporal bone appearing in the mildest forms of osteogenesis imperfecta, correlate these with audiometric results and discuss the possible surgical treatments available. We present three patients suffering hearing loss due to osteogenesis imperfecta type 1 to various functional degrees. All patients underwent an audiological, medical and radiological evaluation and were then treated with different surgical procedures. The patients presented mild, severe and profound mixed hearing losses and the radiological images showed extensive areas of demineralization affecting the ossicular chain and removal of protection for the vital structures inside the temporal bone. Also, the cochlea showed otic capsule demineralization, dehiscence, distortions and even destructions. The various surgical treatments, indicated under current international criteria, obtained limited functional results. This study reviews the need to evaluate the current surgical criteria for this specific condition.

Posibilidades de tratamiento quirúrgico de la hipoacusia en pacientes afectados de osteogénesis imperfecta / Surgical options for hearing loss in patients with osteogenesis imperfecta

El objetivo del estudio es presentar las extensas y severas lesiones óticas que acontecen en la forma más leve de osteogénesis imperfecta, correlacionarlas con las alteraciones audiométricas y discutir las posibilidades quirúrgicas disponibles. Se presenta a 3 pacientes afectados de osteogénesis imperfecta tipo 1 con hipoacusia en distintos estadios funcionales. Se realizó a cada paciente estudio audiológico, médico y radiológico, y se sometieron a distintos tratamientos quirúrgicos. Los pacientes presentaron hipoacusias mixtas de carácter moderado, severo y profundo, imágenes radiológicas con extensas áreas de desmineralización que afectaban la cadena osicular y con desprotección de las estructuras vitales alojadas en el peñasco temporal, desmineralización de la cápsula ótica, dehiscencias, distorsiones y destrucciones cocleares. Los tratamientos quirúrgicos realizados, e indicados según los criterios actualmente aceptados, obtuvieron escasos resultados funcionales. El presente estudio plantea la necesidad de evaluar los criterios quirúrgicos específicos para esta enfermedad(AU)

The aim of the study is to present the severe, extensive lesions in the temporal bone appearing in the mildest forms of osteogenesis imperfecta, correlate these with audiometric results and discuss the possible surgical treatments available. We present three patients suffering hearing loss due to osteogenesis imperfecta type 1 to various functional degrees. All patients underwent an audiological, medical and radiological evaluation and were then treated with different surgical procedures. The patients presented mild, severe and profound mixed hearing losses and the radiological images showed extensive areas of demineralization affecting the ossicular chain and removal of protection for the vital structures inside the temporal bone. Also, the cochlea showed otic capsule demineralization, dehiscence, distortions and even destructions. The various surgical treatments, indicated under current international criteria, obtained limited functional results. This study reviews the need to evaluate the current surgical criteria for this specific condition(AU)