Diagnosis of erosive tooth wear

The clinical diagnosis 'erosion' is made from characteristic deviations from the original anatomical tooth morphology, thus, distinguishing acid induced tissue loss from other forms of wear. Primary pathognomonic features are shallow concavities on smooth surfaces occurring coronal from the enamel-cementum junction. Problems from diagnosing occlusal surfaces and exposed dentine are discussed. Indices for recording erosive wear include morphological as well as quantitative criteria. Currently, various indices are used making the comparison of prevalence studies difficult. The most important and frequently used indices are described. In addition to recording erosive lesions, the assessment of progression is important as the indication of treatment measures depends on erosion activity. A number of evaluated and sensitive methods for in vitro and in situ approaches are available, but the fundamental problem for their clinical use is the lack of re-identifiable reference areas. Tools for clinical monitoring are described.

Angiopoietin-2 causes pericyte dropout in the normal retina: evidence for involvement in diabetic retinopathy

Pericyte loss is an early pathologic feature of diabetic retinopathy, consistently present in retinae of diabetic humans and animals. Because pericyte recruitment and endothelial cell survival are controlled, in part, by the angiopoietin/Tie2 ligand/receptor system, we studied the expression of angiopoietin-2 and -1 in relation to the evolution of pericyte loss in diabetic rat retinae, using quantitative retinal morphometry, and in retinae from mice with heterozygous angiopoietin deficiency (Ang-2 LacZ knock-in mice). Finally, recombinant angiopoietin-2 was injected into eyes of nondiabetic rats, and pericyte numbers were quantitated in retinal capillaries. Angiopoietin-1 protein was present in the normal maturing retina and was upregulated 2.5-fold in diabetic retinae over 3 months of diabetes. In contrast, angiopoietin-2 protein was consistently upregulated more than 30-fold in the retinae of diabetic rats, preceding the onset of pericyte loss. Heterozygous angiopoietin-2 deficiency completely prevented diabetes-induced pericyte loss and reduced the number of acellular capillary segments. Injection of angiopoietin-2 into the eyes of normal rats induced a dose-dependent pericyte loss. These data show that upregulation of angiopoietin-2 plays a critical role in the loss of pericytes in the diabetic retina.

[The model project "newborn auditory screening" in the Upper Palatinate: high process and result quality of an interdisciplinary concept]

BACKGROUND: In May 2003, a newborn auditory screening program was initiated in the Upper Palatinate. METHODS: Sequential OAE- and BERA-screening was conducted in all hospitals with obstetric facilities. The Screening Center at the Public Health Authority was responsible for the coordination of the screening process, completeness of participation, the follow-up of all subjects with a positive screening test and the quality of instrumental screening. RESULTS: A total of 96% of 17,469 newborns were screened. The referral rate at discharge was 1.6% (0.4% for bilateral positive findings). For 97% of the positive screening results, a definite diagnosis to confirm or exclude hearing loss was achieved; for 43% only after intervention by the Screening Center. Fifteen children with profound bilateral hearing impairment were identified of whom eight were only detected by the intervention of the Screening Center. CONCLUSION: The effective structures established in the Upper Palatinate provide a standard for the quality of neonatal auditory screening achievable in Germany.

Robust postmortem survival of murine vestibular and cochlear stem cells

Potential treatment strategies of neurodegenerative and other diseases with stem cells derived from nonembryonic tissues are much less subjected to ethical criticism than embryonic stem cell-based approaches. Here we report the isolation of inner ear stem cells, which may be useful in cell replacement therapies for hearing loss, after protracted postmortem intervals. We found that neonatal murine inner ear tissues, including vestibular and cochlear sensory epithelia, display remarkably robust cellular survival, even 10 days postmortem. Similarly, isolation of sphere-forming stem cells was possible up to 10 days postmortem. We detected no difference in the proliferation and differentiation potential between stem cells isolated directly after death and up to 5 days postmortem. At longer postmortem intervals, we observed that the potency of sphere-derived cells to spontaneously differentiate into mature cell types diminishes prior to the cells losing their potential for self-renewal. Three-week-old mice also displayed sphere-forming stem cells in all inner ear tissues investigated up to 5 days postmortem. In summary, our results demonstrate that postmortem murine inner ear tissue is suited for isolation of stem cells.

Differential distribution of stem cells in the auditory and vestibular organs of the inner ear

The adult mammalian cochlea lacks regenerative capacity, which is the main reason for the permanence of hearing loss. Vestibular organs, in contrast, replace a small number of lost hair cells. The reason for this difference is unknown. In this work we show isolation of sphere-forming stem cells from the early postnatal organ of Corti, vestibular sensory epithelia, the spiral ganglion, and the stria vascularis. Organ of Corti and vestibular sensory epithelial stem cells give rise to cells that express multiple hair cell markers and express functional ion channels reminiscent of nascent hair cells. Spiral ganglion stem cells display features of neural stem cells and can give rise to neurons and glial cell types. We found that the ability for sphere formation in the mouse cochlea decreases about 100-fold during the second and third postnatal weeks; this decrease is substantially faster than the reduction of stem cells in vestibular organs, which maintain their stem cell population also at older ages. Coincidentally, the relative expression of developmental and progenitor cell markers in the cochlea decreases during the first 3 postnatal weeks, which is in sharp contrast to the vestibular system, where expression of progenitor cell markers remains constant or even increases during this period. Our findings indicate that the lack of regenerative capacity in the adult mammalian cochlea is either a result of an early postnatal loss of stem cells or diminishment of stem cell features of maturing cochlear cells.

Otologic manifestations in Samter's syndrome

OBJECTIVE: It was the aim of this study to investigate the prevalence of otologic manifestations in a cohort of Samter's syndrome patients (nasal polyps with chronic rhinosinusitis, aspirin intolerance and asthma). METHODS: We analyzed a retrospective and prospective case review from 1995 to 2005, performed in the otorhinolaryngology outpatient clinic of a tertiary referral center. Ear history, clinical examinations, treatment and outcome were evaluated using office and hospital records in 23 cases. All subjects completed a questionnaire. RESULTS: In 6 cases (26%), otological manifestations with ear pressure and conductive hearing loss occurred during an advanced stage of Samter's syndrome (>5 years after onset of the first nasal symptoms) partially responsive to systemic steroids. CONCLUSION: Recognition of the association between Samter's syndrome and otological disease is important (26% of the cases) because it could also be responsive to systemic steroids which prevent progression to irreversible hearing loss or infectious otomastoiditis.

External auditory canal cholesteatoma: reassessment of and amendments to its categorization, pathogenesis, and treatment in 34 patients

OBJECTIVE: External auditory canal cholesteatoma (EACC) is a rarity. Although there have been numerous case reports, there are only few systematic analyses of case series, and the pathogenesis of idiopathic EACC remains enigmatic. STUDY DESIGN: In a tertiary referral center for a population of 1.5 million inhabitants, 34 patients with 35 EACC (13 idiopathic [1 bilateral] and 22 secondary) who were treated between 1994 and 2006 were included in the study. RESULTS: EACC cardinal symptoms were longstanding otorrhea (65%) and dull otalgia (12%). Focal bone destruction in the external auditory canal with retained squamous debris and an intact tympanic membrane were characteristic. Only 27% of the patients showed conductive hearing loss exceeding 20 dB. Patients with idiopathic EACC had lesions typically located on the floor of the external auditory canal and were older, and the mean smoking intensity was also greater (p < 0.05) compared with patients with secondary EACC. The secondary lesions were assigned to categories (poststenotic [n = 6], postoperative [n = 6], and posttraumatic EACC [n = 4]) and rare categories (radiogenic [n = 2], postinflammatory [n = 1], and postobstructive EACC [n = 1]). In addition, we describe 2 patients with EACC secondary to the complete remission of a Langerhans cell histiocytosis of the external auditory canal. Thirty of 34 patients were treated surgically and became all free of recurrence, even after extensive disease. DISCUSSION: For the development of idiopathic EACC, repeated microtrauma (e.g., microtrauma resulting from cotton-tipped applicator abuse or from hearing aids) and diminished microcirculation (e.g., from smoking) might be risk factors. A location other than in the inferior portion of the external auditory canal indicates a secondary form of the disease, as in the case of 2 patients with atypically located EACC after years of complete remission of Langerhans cell histiocytosis, which we consider as a new posttumorous category and specific late complication of this rare disease.

Isolation of sphere-forming stem cells from the mouse inner ear

The mammalian inner ear has very limited ability to regenerate lost sensory hair cells. This deficiency becomes apparent when hair cell loss leads to hearing loss as a result of either ototoxic insult or the aging process. Coincidently, with this inability to regenerate lost hair cells, the adult cochlea does not appear to harbor cells with a proliferative capacity that could serve as progenitor cells for lost cells. In contrast, adult mammalian vestibular sensory epithelia display a limited ability for hair cell regeneration, and sphere-forming cells with stem cell features can be isolated from the adult murine vestibular system. The neonatal inner ear, however, does harbor sphere-forming stem cells residing in cochlear and vestibular tissues. Here, we provide protocols to isolate sphere-forming stem cells from neonatal vestibular and cochlear sensory epithelia as well as from the spiral ganglion. We further describe procedures for sphere propagation, cell differentiation, and characterization of inner ear cell types derived from spheres. Sphere-forming stem cells from the mouse inner ear are an important tool for the development of cellular replacement strategies of damaged inner ears and are a bona fide progenitor cell source for transplantation studies.

Two cases of trisomy 16 mosaicism ascertained postnatally

Postnatally ascertained trisomy 16 mosaicism is a rare diagnosis, with only three reported cases to date with no defined clinical phenotype. Trisomy 16 mosaicism diagnosed prenatally is common and associated with variable pregnancy outcomes ranging from stillbirth with multiple congenital abnormalities to an apparently normal newborn, making the genetic counseling very challenging. It is not clear whether uniparental disomy (UPD) 16 contributes to the phenotype, although it has been suggested that maternal UPD 16 affects the rate of intra-uterine growth retardation (IUGR) and congenital anomalies. We report on two further cases of trisomy 16 mosaicism confined to fibroblasts diagnosed postnatally. Patient 1 presented at birth with severe hypospadias, unilateral postaxial polydactyly, and different hair color with midline demarcation. His growth and development were normal at 11 months of age. Patient 2 was born with IUGR, significant craniofacial and body asymmetry, asymmetric skin hyperpigmentation, unilateral hearing loss, scoliosis, VSD, unexplained dilated cardiomyopathy, feeding difficulties, failure to thrive, and recurrent respiratory tract infections. She died at 7 months of age from respiratory failure. These two further cases of postnatally diagnosed trisomy 16 mosaicism highlight the variability of clinical features and outcome in this diagnosis. While Patient 2 presented with typical features of chromosomal mosaicism, Patient 1 had mild and transient features with essentially normal outcome, suggesting that trisomy 16 mosaicism may be under-diagnosed.

Microvascular decompression for trigeminal neuralgia in the elderly: long-term treatment outcome and comparison with younger patients

OBJECTIVE: Multiple studies have proved that microvascular decompression (MVD) is the treatment of choice in cases of medically refractory trigeminal neuralgia (TN). In the elderly, however, the surgical risks related to MVD are assumed to be unacceptably high and various alternative therapies have been proposed. We evaluated the outcomes of MVD in patients aged older than 65 years of age and compared them with the outcomes in a matched group of younger patients. The focus was on procedure-related morbidity rate and long-term outcome. METHODS: This was a retrospective study of 112 patients with TN operated on consecutively over 22 years. The main outcome measures were immediate and long-term postoperative pain relief and neurological status, especially function of trigeminal, facial, and cochlear nerves, as well as surgical complications. A questionnaire was used to assess long-term outcome: pain relief, duration of a pain-free period, need for pain medications, time to recurrence, pain severity, and need for additional treatment. RESULTS: The mean age was 70.35 years. The second and third branches of the trigeminal nerve were most frequently affected (37.3%). The mean follow-up period was 90 months (range, 48-295 months). Seventy-five percent of the patients were completely pain free, 11% were never pain free, and 14% experienced recurrences. No statistically significant differences existed in the outcome between the younger and older patient groups. Postoperative morbidity included trigeminal hypesthesia in 6.25%, hypacusis in 5.4%, and complete hearing loss, vertigo, and partial facial nerve palsy in 0.89% each. Cerebrospinal fluid leak and meningitis occurred in 1 patient each. There were no mortalities in both groups. CONCLUSION: MVD for TN is a safe procedure even in the elderly. The risk of serious morbidity or mortality is similar to that in younger patients. Furthermore, no significant differences in short- and long-term outcome were found. Thus, MVD is the treatment of choice in patients with medically refractory TN, unless their general condition prohibits it.

Cochlear implantation in children and adults in Switzerland

The cochlear implant (CI) is one of the most successful neural prostheses developed to date. It offers artificial hearing to individuals with profound sensorineural hearing loss and with insufficient benefit from conventional hearing aids. The first implants available some 30 years ago provided a limited sensation of sound. The benefit for users of these early systems was mostly a facilitation of lip-reading based communication rather than an understanding of speech. Considerable progress has been made since then. Modern, multichannel implant systems feature complex speech processing strategies, high stimulation rates and multiple sites of stimulation in the cochlea. Equipped with such a state-of-the-art system, the majority of recipients today can communicate orally without visual cues and can even use the telephone. The impact of CIs on deaf individuals and on the deaf community has thus been exceptional. To date, more than 300,000 patients worldwide have received CIs. In Switzerland, the first implantation was performed in 1977 and, as of 2012, over 2,000 systems have been implanted with a current rate of around 150 CIs per year. The primary purpose of this article is to provide a contemporary overview of cochlear implantation, emphasising the situation in Switzerland.

Multicenter study with a direct acoustic cochlear implant

OBJECTIVE To confirm the clinical efficacy and safety of a direct acoustic cochlear implant. STUDY DESIGN Prospective multicenter study. SETTING The study was performed at 3 university hospitals in Europe (Germany, The Netherlands, and Switzerland). PATIENTS Fifteen patients with severe-to-profound mixed hearing loss because of otosclerosis or previous failed stapes surgery. INTERVENTION Implantation with a Codacs direct acoustic cochlear implant investigational device (ID) combined with a stapedotomy with a conventional stapes prosthesis MAIN OUTCOME MEASURES Preoperative and postoperative (3 months after activation of the investigational direct acoustic cochlear implant) audiometric evaluation measuring conventional pure tone and speech audiometry, tympanometry, aided thresholds in sound field and hearing difficulty by the Abbreviated Profile of Hearing Aid Benefit questionnaire. RESULTS The preoperative and postoperative air and bone conduction thresholds did not change significantly by the implantation with the investigational Direct Acoustic Cochlear Implant. The mean sound field thresholds (0.25-8 kHz) improved significantly by 48 dB. The word recognition scores (WRS) at 50, 65, and 80 dB SPL improved significantly by 30.4%, 75%, and 78.2%, respectively, after implantation with the investigational direct acoustic cochlear implant compared with the preoperative unaided condition. The difficulty in hearing, measured by the Abbreviated Profile of Hearing Aid Benefit, decreased by 27% after implantation with the investigational direct acoustic cochlear implant. CONCLUSION Patients with moderate-to-severe mixed hearing loss because of otosclerosis can benefit substantially using the Codacs investigational device.

The SLC1 high-affinity glutamate and neutral amino acid transporter family

Glutamate transporters play important roles in the termination of excitatory neurotransmission and in providing cells throughout the body with glutamate for metabolic purposes. The high-affinity glutamate transporters EAAC1 (SLC1A1), GLT1 (SLC1A2), GLAST (SLC1A3), EAAT4 (SLC1A6), and EAAT5 (SLC1A7) mediate the cellular uptake of glutamate by the co-transport of three sodium ions (Na(+)) and one proton (H(+)), with the counter-transport of one potassium ion (K(+)). Thereby, they protect the CNS from glutamate-induced neurotoxicity. Loss of function of glutamate transporters has been implicated in the pathogenesis of several diseases, including amyotrophic lateral sclerosis and Alzheimer's disease. In addition, glutamate transporters play a role in glutamate excitotoxicity following an ischemic stroke, due to reversed glutamate transport. Besides glutamate transporters, the SLC1 family encompasses two transporters of neutral amino acids, ASCT1 (SLC1A4) and ASCT2 (SLC1A5). Both transporters facilitate electroneutral exchange of amino acids in neurons and/or cells of the peripheral tissues. Some years ago, a high resolution structure of an archaeal homologue of the SLC1 family was determined, followed by the elucidation of its structure in the presence of the substrate aspartate and the inhibitor d,l-threo-benzyloxy aspartate (d,l-TBOA). Historically, the first few known inhibitors of SLC1 transporters were based on constrained glutamate analogs which were active in the high micromolar range but often also showed off-target activity at glutamate receptors. Further development led to the discovery of l-threo-β-hydroxyaspartate derivatives, some of which effectively inhibited SLC1 transporters at nanomolar concentrations. More recently, small molecule inhibitors have been identified whose structures are not based on amino acids. Activators of SLC1 family members have also been discovered but there are only a few examples known.

Diagnosis of erosive tooth wear.

The clinical diagnosis 'erosion' is made from characteristic deviations from the original anatomical tooth morphology, thus distinguishing acid-induced tissue loss from other forms of wear. Primary pathognomonic features are shallow concavities on smooth surfaces occurring coronal from the enamel-cementum junction. Problems from diagnosing occlusal surfaces and exposed dentine are discussed. Indices for recording erosive wear include morphological as well as quantitative criteria. Currently, various indices are used, each having their virtues and flaws, making the comparison of prevalence studies difficult. The Basic Erosive Wear Examination (BEWE) is described, which is intended to provide an easy tool for research as well as for use in general dental practice. The cumulative score of this index is the sum of the most severe scores obtained from all sextants and is linked to suggestions for clinical management. In addition to recording erosive lesions, the assessment of progression is important as the indication of treatment measures depends on erosion activity. A number of evaluated and sensitive methods for in vitro and in situ approaches are available, but the fundamental problem for their clinical use is the lack of reidentifiable reference areas. Tools for clinical monitoring are described.

Benefit of a Contralateral Routing of Signal Device for Unilateral Cochlear Implant Users.

Objective: To investigate objective and subjective effects of an adjunctive contralateral routing of signal (CROS) device at the untreated ear in patients with a unilateral cochlear implant (CI). Design: Prospective study of 10 adult experienced unilateral CI users with bilateral severe-to-profound hearing loss. Speech in noise reception (SNR) and sound localization were measured with and without the additional CROS device. SNR was measured by applying speech signals at the untreated/CROS side while noise signals came from the front (S90N0). For S0N90, signal sources were switched. Sound localization was measured in a 12-loudspeaker full circle setup. To evaluate the subjective benefit, patients tried the device for 2 weeks at home, then filled out the abbreviated Speech, Spatial and Qualities of Hearing Scale as well as the Bern benefit in single-sided deafness questionnaires. Results: In the setting S90N0, all patients showed a highly significant SNR improvement when wearing the additional CROS device (mean 6.4 dB, p < 0.001). In the unfavorable setting S0N90, only a minor deterioration of speech understanding was noted (mean -0.66 dB, p = 0.54). Sound localization did not improve substantially with CROS. In the two questionnaires, 12 of 14 items showed an improvement in mean values, but none of them was statistically significant. Conclusion: Patients with unilateral CI benefit from a contralateral CROS device, particularly in a noisy environment, when speech comes from the CROS ear side. © 2014 S. Karger AG, Basel.