Subtotal Petrosectomy and Cochlear Implantation in Children With Chronic Suppurative Otitis Media: A Single Institutional Experience.

BACKGROUND AND OBJECTIVES: Chronic suppurative otitis media (CSOM) with or without cholesteatoma is a frequent chronic inflammatory condition in children, which may lead to severe hearing loss that affects speech development. Treatment of recurrent CSOM associated with unserviceable hearing requires a specialized approach with regard to disease eradication and hearing rehabilitation. In this study, we investigated the advantages of subtotal petrosectomy (SP) combined with cochlear implantation (CI) in children with CSOM associated with unserviceable hearing and describe our experience with regard to the efficacy of this method, together with a literature review. SUBJECTS AND METHODS: SP with sequential or simultaneous CI was performed in three children (four ears), and postoperative audiometric data were recorded. RESULTS: The study included two male and one female patient. Mean age at the time of SP was 10.75 years (7-13 years). Sequential implantation was performed in three ears. Facial nerve palsy occurred after SP in one patient. The latest word recognition scores of Cases 1, 2, and 3 were 80% (at 60 dB), 75% (at 60 dB), and 70% (at 50 dB) and 90% (at 50 dB), respectively. CONCLUSIONS: SP with CI may be safe and reliable in children with CSOM associated with unserviceable hearing.

TUBB4B gene mutation in Leber phenotype of congenital amaurosis syndrome associated with early-onset deafness.

Beta-tubulin 4B isotype is one of the subunits of microtubules encoded by TUBB4B gene on chromosome 9, which is responsible for the maintenance of microtubule stability. In humans, mutations in microtubule-encoding genes have been associated with several tubulinopathies with very heterogeneous symptoms. So far, only two missense mutations in TUBB4B gene have been found to have pathological implications in this disorder. Here we report a Hungarian family with three affected members, mother and her 12- and 14-year-old children, who suffer from ophthalmologic and hearing impairments probably due to c.1171C > T missense variant in the TUBB4B gene. The presented case is the second report, and unique in the literature because of three affected family members carrying the same mutation and the family provides evidence for a quite similar but not identical phenotype of LCAEOD in subjects carrying this mutation.

Effects of Chlorine Dioxide on Oral Hygiene - A Systematic Review and Meta-analysis.

BACKGROUND: Effective and selective oral rinses are required in the daily medical and dental practice. Currently mouthwashes used have substantial side effects. OBJECTIVES: Our aim was to evaluate the efficacy of chlorine dioxide-containing mouthwashes in comparison with other previously established mouth rinses in healthy adults using oral hygiene indices. METHODS: This work was registered in PROSPERO (CRD42018099059) and carried out using multiple databases and reported according to the PRISMA statement. The search terms used were "chlorine dioxide" AND "oral", and only randomised controlled trials (RCTs) were included. The primary outcome was the alteration of the plaque index (PI), while the secondary outcomes were the gingival index (GI) and bacterial counts. For the risk of bias assessment, the Cochrane Risk of Bias Tool was used. Statistical analysis for data heterogeneity was performed by Q-value and I2-tests. RESULTS: 364 articles were found in the databases. After the selection process, only five RCTs were eligible for meta-analysis. Data heterogeneity was low. There were no statistical differences in effectiveness between chlorine dioxide and other effective mouth rinses in PI (0.720±0.119 vs 0.745±0.131; 95%; confidence intervals (CIs): 0.487-0.952 vs 0.489-1.001, respectively) and GI (0.712±0.130 vs 0.745±0.131; 95% CIs: 0.457-0.967 vs 0.489- 1.001, respectively) and also in bacterial counts. CONCLUSION: Chlorine dioxide reduces both plaque and gingival indices and bacterial counts in the oral cavity similar to other routinely used oral rinses, however, the evidence supporting this outcome is very limited. Therefore, further large scale RCTs are needed to decrease the risk of bias.

Endoscopic versus microscopic stapes surgery outcomes: A meta-analysis and systematic review.

OBJECTIVE: Compare intraoperative and postoperative outcomes of endoscopic and microscopic stapes surgery to provide objective evidence on whether the former is a better alternative than the latter. METHODS: We performed a systematic review and meta-analysis for studies that compared endoscopic stapes surgery with microscopic stapes surgery. Only studies that met predetermined criteria were selected and assessed for bias and quality. Primary outcomes were postoperative air-bone gap (ABG) and chorda tympani nerve injury. Secondary outcomes were average operating time, tympanic membrane (TM) perforation, and postoperative taste disturbance, pain, and dizziness. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes and weighted mean difference (WMD) with 95% CI for continuous outcomes. A confidence interval starting above 1.0 was considered as statistically significant. I2 and χ2 tests were used to quantify statistical heterogeneity. We used funnel plots to look for publication bias and performed a sensitivity analysis. RESULTS: Six nonrandomized cohort studies were eligible. The primary outcomes were ABG < 10 dB: OR = 1.80 (95% CI: 0.96 to 3.38), ABG = 11 dB to 20 dB: OR = 1.49 (95% CI: 0.76 to 2.93), ABG > 20 dB: OR = 2.51 (95% CI: 0.77 to 8.22), and chorda tympani injury: OR = 3.51 (95% CI: 1.55 to 7.93). Secondary outcomes were taste: OR = 2.36 (95% CI: 1.01 to 5.51), average operation time: WMD = 0.14 (95% CI: -11.69 to 11.98), TM perforation: OR = 1.70 (95% CI: 0.44 to 6.58); pain: OR = 0.84 (95% CI: 0.36 to 1.96), and dizziness: OR = 2.15 (95% CI: 0.94 to 4.89). CONCLUSIONS: Endoscopic stapes surgery is a valid alternative to the microscope. LEVEL OF EVIDENCE: 2a Laryngoscope, 130: 2019-2027, 2020.

Hearing impairment and associated morphological changes in pituitary adenylate cyclase activating polypeptide (PACAP)-deficient mice.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a regulatory and cytoprotective neuropeptide, its deficiency implies accelerated aging in mice. It is present in the auditory system having antiapoptotic effects. Expression of Ca2+-binding proteins and its PAC1 receptor differs in the inner ear of PACAP-deficient (KO) and wild-type (WT) mice. Our aim was to elucidate the functional role of PACAP in the auditory system. Auditory brainstem response (ABR) tests found higher hearing thresholds in KO mice at click and low frequency burst stimuli. Hearing impairment at higher frequencies showed as reduced ABR wave amplitudes and latencies in KO animals. Increase in neuronal activity, demonstrated by c-Fos immunolabeling, was lower in KO mice after noise exposure in the ventral and dorsal cochlear nuclei. Noise induced neuronal activation was similar in further relay nuclei of the auditory pathway of WT and KO mice. Based on the similar inflammatory and angiogenic protein profile data from cochlear duct lysates, neither inflammation nor disturbed angiogenesis, as potential pathological components in sensorineural hearing losses, seem to be involved in the pathomechanism of the presented functional and morphological changes in PACAP KO mice. The hearing impairment is probably concomitant with the markedly accelerated aging processes in these animals.

[First experiences with Cochlear Implant Function Index (CIFI) in Hungary]. / A Cochlearis Implantáltak Funkcionális Indexe (CIFI) magyarországi bevezetésével szerzett kezdeti tapasztalatok.

Introduction: The success of cochlear implantation can be evaluated with audiological measurements and quality of life questionnaires. Aim: Our aim was to translate and introduce the Cochlear Implant Function Index (CIFI) test to analyze the physical, psychological and social state of our cochlear implant patients. Method: Between 01. 11. 2016 and 31. 05. 2018, 30 patients filled the questionnaire before and 6 and 12 months after the implantation. Results and conclusion: Results showed a remarkable improvement in the quality of life in several patients even after 6 months. Further improvements could be measured after 12 months. Orv Hetil. 2019; 160(33): 1296-1303.

[Comparative evaluation of vertigo in patients after stapedotomy and stapedectomy]. / Posztoperatív vertigo vizsgálata stapedotomián és stapedectomián átesett betegeknél.

INTRODUCTION AND AIM: The reason of gradually developing conductive hearing loss in otosclerotic patients is the ossification of the stapes footplate to the surrounding bony structures and the therapy of stapes fixation is mainly surgical. In stapedotomy the footplate of the stapes is fenestrated with laser and microdrill in a diameter of 0.8 mm, whereas in stapedectomy there is complete removal of the footplate followed by the reconstruction of the ossicular chain. In the early postoperative period, temporary vertigo is frequently recorded which significantly influences the recovery. METHOD: In the Department of Otorhinolaryngology, University of Pécs both stapedectomy and stapedotomy were performed on a daily basis between 01.02.2010 and 15.03.2012. Our study focused on comparing the degree of postoperative vertigo after the two types of surgery. We hypothesized that the smaller fenestration of the stapes footplate during stapedotomy limits exposure to the inner ear reducing the severity of dizziness. Vertigo was evaluated subjectively with a retrospective questionnaire and objectively with static posturography. RESULTS: On the 1st postoperative day, significantly fewer patients reported vertigo in the stapedotomy group and with significantly lower intensity. Results of the questionnaire regarding the later postoperative period showed no significant differences between the groups. Based on the analysis of the posturography test results, no significant difference was detected between the postoperative stability of the two groups. Results of the questionnaire and the posturography showed no correlation. Posturography test results did not confirm the presence of subjective vertigo. CONCLUSION: Many factors may play a role in the development of vertigo after stapes surgery, but the type of intervention does not influence it. Orv Hetil. 2017; 158(38): 1503-1511.

[Body image and body image distortion]. / A testképtol a testképzavarig.

The aim of this literature review is to integrate the results of various studies regarding body image and body image distortion into a unified framework. The concept of body image is complex and can be interpreted from multiple points of view. The first part of the study touches upon different age characteristics, attentional focus on the body, the early and important role of the body in identity formation, specific features in adolescence, gender differences, and the often-observed stability of body image (distortion), which may be present as a (trait) marker throughout the lifespan. The second part focuses on the organization of body image. The results of different studies on cognitive information processing are reviewed, the question of perceptual accuracy is addressed and the concepts of embodiment are examined. The third topic is body image distortion. First, the concept is contextualized along different continua, then discussed in a clinical sense along with the complexity of diagnostic methods, as well as the state and trait aspects of body image distortion. Orv Hetil. 2017; 158(19): 723-730.

Decreased calcium pump expression in human erythrocytes is connected to a minor haplotype in the ATP2B4 gene.

Plasma membrane Ca2+-ATPases are key calcium exporter proteins in most tissues, and PMCA4b is the main calcium transporter in the human red blood cells (RBCs). In order to assess the expression level of PMCA4b, we have developed a flow cytometry and specific antibody binding method to quantitatively detect this protein in the erythrocyte membrane. Interestingly, we found several healthy volunteers showing significantly reduced expression of RBC-PMCA4b. Western blot analysis of isolated RBC membranes confirmed this observation, and indicated that there are no compensatory alterations in other PMCA isoforms. In addition, reduced PMCA4b levels correlated with a lower calcium extrusion capacity in these erythrocytes. When exploring the potential genetic background of the reduced PMCA4b levels, we found no missense mutations in the ATP2B4 coding regions, while a formerly unrecognized minor haplotype in the predicted second promoter region closely correlated with lower erythrocyte PMCA4b protein levels. In recent GWA studies, SNPs in this ATP2B4 haplotype have been linked to reduced mean corpuscular hemoglobin concentrations (MCHC), and to protection against malaria infection. Our data suggest that an altered regulation of gene expression is responsible for the reduced RBC-PMCA4b levels that is probably linked to the development of human disease-related phenotypes.

Alterations of membrane protein expression in red blood cells of Alzheimer's disease patients.

Preventive measures, prognosis, or selected therapy in multifactorial maladies, including Alzheimer's disease (AD), require the application of a wide range of diagnostic assays. There is a large unmet need for relatively simple, blood-based biomarkers in this regard. We have recently developed a rapid and reliable flow cytometry and antibody-based method for the quantitative measurement of various red blood cell (RBC) membrane proteins from a drop of blood. Here, we document that the RBC expression of certain membrane proteins, especially that of the GLUT1 transporter and the insulin receptor (INSR), is significantly higher in AD patients than in age-matched healthy subjects. The observed differences may reflect long-term metabolic alterations relevant in the development of AD. These findings may pave the way for a diagnostic application of RBC membrane proteins as relatively stable and easily accessible personalized biomarkers in AD.

Cell surface membrane proteins as personalized biomarkers: where we stand and where we are headed.

Personalized medicine requires the development of a wide array of biomarker diagnostic assays, reflecting individual variations and thus allowing tailored therapeutic interventions. Membrane proteins comprise approximately 30% of total human proteins; they play a key role in various physiological functions and pathological conditions, although, currently, only a limited number of membrane proteins are applied as biomarkers. In many normal tissues, cell surface membrane proteins are not easily accessible for diagnostic sampling, and tumor-derived membrane preparations - while serving as potential tumor biomarkers - may not reflect physiological protein expression. In addition to post-translational modifications, which may include glycosylation, phosphorylation and lipid modifications, the trafficking of membrane proteins is also regulated. Moreover, a tight cellular quality control monitors membrane protein maturation, and continuous removal and reinsertion, involving special signaling systems, occurs in many cases. However, cell surface membrane proteins already serve as valuable prognostic and predicative biomarkers, for example, in hematological and immunological diseases, by the determination of the cluster of differentiation markers. In this review, we demonstrate the relevance of cell surface membrane biomarkers in various diseases and call attention to the potential application of red blood cell (erythrocyte) membrane proteins in this regard. Surprisingly, red blood cells express hundreds of membrane proteins, which seem to reflect a general genetic and regulatory background, and may serve as relatively stable and easily accessible personalized membrane biomarkers. Quantitative membrane protein detection in red blood cells by flow cytometry may bring a breakthrough in this regard.

Expression levels of the ABCG2 multidrug transporter in human erythrocytes correspond to pharmacologically relevant genetic variations.

We have developed a rapid, simple and reliable, antibody-based flow cytometry assay for the quantitative determination of membrane proteins in human erythrocytes. Our method reveals significant differences between the expression levels of the wild-type ABCG2 protein and the heterozygous Q141K polymorphic variant. Moreover, we find that nonsense mutations on one allele result in a 50% reduction in the erythrocyte expression of this protein. Since ABCG2 polymorphisms are known to modify essential pharmacokinetic parameters, uric acid metabolism and cancer drug resistance, a direct determination of the erythrocyte membrane ABCG2 protein expression may provide valuable information for assessing these conditions or for devising drug treatments. Our findings suggest that erythrocyte membrane protein levels may reflect genotype-dependent tissue expression patterns. Extension of this methodology to other disease-related or pharmacologically important membrane proteins may yield new protein biomarkers for personalized diagnostics.

Angiotensin II increases the permeability and PV-1 expression of endothelial cells.

Angiotensin II (ANG II), the major effector molecule of the renin-angiotensin system (RAS), is a powerful vasoactive mediator associated with hypertension and renal failure. In this study the permeability changes and its morphological attributes in endothelial cells of human umbilical vein (HUVECs) were studied considering the potential regulatory role of ANG II. The effects of ANG II were compared with those of vascular endothelial growth factor (VEGF). Permeability was determined by 40 kDa FITC-Dextran and electrical impedance measurements. Plasmalemmal vesicle-1 (PV-1) mRNA levels were measured by PCR. Endothelial cell surface was studied by atomic force microscopy (AFM), and caveolae were visualized by transmission electron microscopy (TEM) in HUVEC monolayers. ANG II (10(-7) M), similarly to VEGF (100 ng/ml), increased the endothelial permeability parallel with an increase in the number of cell surface openings and caveolae. AT1 and VEGF-R2 receptor blockers (candesartan and ZM-323881, respectively) blunted these effects. ANG II and VEGF increased the expression of PV-1, which could be blocked by candesartan or ZM-323881 pretreatments and by the p38 mitogem-activated protein (MAP) kinase inhibitor SB-203580. Additionally, SB-203580 blocked the increase in endothelial permeability and the number of surface openings and caveolae. In conclusion, we have demonstrated that ANG II plays a role in regulation of permeability and formation of cell surface openings through AT1 receptor and PV-1 protein synthesis in a p38 MAP kinase-dependent manner in endothelial cells. The surface openings that increase in parallel with permeability may represent transcellular channels, caveolae, or both. These morphological and permeability changes may be involved in (patho-) physiological effects of ANG II.

Necrosis of the long process of the incus following stapes surgery: new anatomical observations.

OBJECTIVES/HYPOTHESIS: The most frequent complication (generally recognized during revision procedures) following seemingly successful stapedotomies and stapedectomies is necrosis of the long process of the incus. This is currently ascribed to a malcrimped stapes prosthesis or to a compromised blood supply of the incus. The two-point fixation can cause a mucosal injury with a resulting toxic reaction, and also osteoclastic activity. An important aspect in the engineering of ideal stapes prostheses is that they should be fixed circularly to the long process of the incus with appropriate strength. The objective of this study was to compare current knowledge relating to the blood supply of the ossicular chain with the present authors' observations on cadaver incudes. Most of the papers dealing with this issue appeared in the mid-20th century. METHODS: The published data were compared with the authors' findings gained from photodocumentation on 100 cadaver incudes. The photos were taken with a Canon EOS 20 digital camera (Canon, Inc., Lake Success, NY) with a 5:1 macro-objective. The long processes of the incudes were examined from four directions under a Leica surface-analyzing microscope (Leica Microsystems GmbH, Wetzlar, Germany). RESULTS: Analysis of the positions of the entrances of the feeding arteries (nutritive foramina) on the incudes revealed 1-4 nutritive foramina on the long processes of 48% (24) of the left-sided incudes and 56% (28) of the right-sided incudes. The positions of these foramina differed, however, from those previously described in the literature. They were mostly located not on the medial side of the incus body or on the short process or on the cranial third of the long processes, but antero-medially, mostly on the middle or cranial third. In 48% of all the incudes examined, an obvious foramen was not observed either in the body or in the long process of the incus. No relationship was discerned between the chronological age of the incus specimens and the numbers and/or locations of the nutritive foramina. In each case, the opening of the foramen was the beginning of a tunnel running obliquely and medially upward through the corticalis of the long process of the incus. The foramina are thought to be capable of ensuring a richer blood supply between the surface and the inside of the long process, allowing the arteries to run in and out. CONCLUSIONS: These observations indicate that conclusions drawn from classical anatomical works appear to need reconsideration. The present authors consider that the reason for the necrosis of the long process of the incus is not a compromised blood supply, except in some exceptional anatomical situations. They discuss the possible reasons why malcrimping may lead to necrosis of the long process of the incus. To prevent such malcrimping, attention is paid to the new generation of prostheses.

Investigation of the effects of PACAP on the composition of tear and endolymph proteins.

Pituitary adenylate cyclase activating polypeptide (PACAP) is widely distributed in ocular tissues, including the lacrimal gland. PACAP has been shown to influence the activity of several exocrine glands, but its effects on the composition of the tear film are not known yet. Similarly, the presence of PACAP has already been shown in the inner ear, but it is not known whether PACAP influences the composition of the endolymph. The aim of the present study was to investigate whether systemic injection of PACAP has any modulatory effects on the protein composition of the tear film and endolymph using chip electrophoresis and mass spectrometry analysis. Tear and endolymph samples were collected from rats and chickens, respectively, at various time points after systemic injection of PACAP. Fluid samples were further processed for chip electrophoretic studies. No difference was found in the protein composition of the endolymph between control and PACAP-treated animals. In contrast, tear samples showed a marked difference after PACAP treatment. Proteins in the molecular range 50-70 kDa, which showed a different chip electropherogram profile in every PACAP-treated sample, were further analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. PACAP treatment induced a repression in certain keratins, while others were induced after PACAP injection. Furthermore, PACAP treatment decreased aldehyde dehydrogenase expression. The present study provides a base for further studies on the in vivo effects of PACAP on the composition of tear film. These investigations may have important clinical relevance because of the noninvasive sample collection, the correlation between tear proteins and ocular diseases, and the possible presence of biomarkers for both ophthalmological and systemic pathological conditions.