Prospective multicentre clinical study on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori.

OBJECTIVES: We report on a large prospective, multicentre clinical investigation on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori. METHODS: Therapy-naive patients (n = 2004) who had undergone routine diagnostic gastroscopy were prospectively included from all geographic regions of Austria. Gastric biopsy samples were collected separately from antrum and corpus. Samples were analysed by histopathology and real-time PCR for genotypic resistance to clarithromycin and quinolones. Clinical and demographic information was analysed in relation to resistance patterns. RESULTS: H. pylori infection was detected in 514 (26%) of 2004 patients by histopathology and confirmed in 465 (90%) of 514 patients by real-time PCR. PCR results were discordant for antrum and corpus in 27 (5%) of 514 patients, indicating inhomogeneous infections. Clarithromycin resistance rates were 17% (77/448) and 19% (84/455), and quinolone resistance rates were 12% (37/310) and 10% (32/334) in antrum and corpus samples, respectively. Combination of test results per patient yielded resistance rates of 21% (98/465) and 13% (50/383) for clarithromycin and quinolones, respectively. Overall, infection with both sensitive and resistant H. pylori was detected in 65 (14%) of 465 patients. CONCLUSIONS: Anatomically inhomogeneous infection with different, multiple H. pylori strains is common. Prospective clinical study design, collection of samples from multiple sites and microbiologic methods that allow the detection of coinfections are mandatory for collection of reliable data on antimicrobial resistance patterns in representative patient populations. (ClinicalTrials.gov identifier: NCT02925091).

De novo mutation of the connexin 26 gene associated with dominant non-syndromic sensorineural hearing loss.

Mutations of the connexin 26 (Cx26) gene cause isolated recessive or dominant hearing loss or both sensorineural hearing impairment and keratoderma. We have identified the first de novo mutation of the Cx26 gene, R75 W, in a sporadic case of isolated profound hearing loss. R75 W has been previously observed in association with hearing impairment and keratoderma in one family and is thus thought to cause both syndromic and non-syndromic hearing loss. This case illustrates the risk of a possible erroneous diagnosis of autosomal recessive hearing loss in a sporadic case.

Improvement in early detection of congenital hearing impairment due to universal newborn hearing screening.

OBJECTIVE: The aim of this study was to determine whether universal newborn hearing screening (UNHS) is effective in increasing the number of children whose hearing impairment is detected early, i.e. within the first 6 months of life. It also investigated whether UNHS contributes most to the early detection of moderately and severely hearing-impaired newborns, as suggested by a recently published report. METHODS: The study consisted of a retrospective analysis of the data of all children born in Tyrol between 1980 and 1999 and having an at least moderate permanent hearing loss in the better ear. RESULTS: The findings are that since UNHS was introduced in some newborn nurseries in 1995, a substantially higher number of hearing-impaired children has been detected early. For the whole sample, the increase of the early detection rate is 39.9%, with a 95% confidence interval of 33.2-46.8% (P<0.0001). For moderate hearing loss the increase is 49.2 with a 95% confidence intervall of 39.6-58.8% (P=0.000). CONCLUSIONS: On the whole, our findings lend support to the view that UNHS is effective in early detection of congenital hearing impairment. We conclude that UNHS provides the greatest benefit for moderately hearing-impaired children who, otherwise, would have been detected last.

Sensorineural hearing loss and the incidence of Cx26 mutations in Austria.

A clinical evaluation and Cx26 mutation analysis was performed in 92 consecutive patients with sensorineural hearing loss in order to delineate the spectrum of genetically caused hearing loss. Among patients of Austrian origin, 53% were classified with hereditary hearing loss. Cx26 mutations were found in 26% of NSHL patients (40% of familial vs 18% of sporadic cases). The mutation 35delG accounted for 52.8% of all presumed GJB2 disease alleles. The second most frequent mutation was L90P (16.7%) having been reported with a prevalence of 0.7-3.5% in other populations. Three novel mutations were found. The novel mutation, R143Q, was associated with dominant high-frequency hearing loss. Pseudodominant transmission of NSHL was seen in four families with Cx26 mutations. A mutation 35delG carrier rate of 0.9% was observed among 672 controls from West-Austria. Cx26 mutations were found associated with mild to profound, and with asymmetric hearing impairment.

[Optimizing hearing screening by transient evoked otoacoustic emissions in newborn infants]. / Optimierung des Hörscreenings mittels Transient evozierter otoakustischer Emissionen (TEOAE) bei Neugeborenen.

One of the major drawbacks using transient evoked otoacoustic emissions (TEOAEs) for hearing screening in newborn infants is the high fail rate in normal-hearing children. The purpose of the present study was to improve the overall performance of the test procedure and reduce of the fail rate. Improvement was obtained by 3 modifications: (1) change of the pass criterion in healthy newborns by requiring TEOAEs in at least one ear and nor both ears, (2) performing the test only after the second post-partum day, and (3) using a second-stage screening prior to hospital discharge in newborns who failed the initial test. In all, 3980 newborns from 2 well-baby clinics and 243 newborns from a neonatal intensive care unit (NICU) were screened using an system ILO-88 system program mode quick-check test was completed in 3820 infants. Considering these modifications, the pass rate of healthy newborns was improved from 79.5% to > 99%, and only 0.7% of the false negative (healthy) newborns required further audiological evaluation. Babies from the NICU failed in 3.8% of the screening tests. Overall, the number of newborns who failed the ILO-88 screening test was significantly reduced and the fail rate minimize when compared to previously published experiences with TEOAEs in new-born hearing screening.

Click-evoked otoacoustic emissions in a child with unilateral deafness.

In a 6-year-old boy with idiopathic unilateral deafness, click-evoked otoacoustic emissions were recorded in both ears with similar amplitudes and time courses. Following stimulation of the deaf ear, no component of auditory-evoked brainstem potentials was recorded. No space-occupying lesion was observed with high-resolution CT. At retest 1 year later these results were unchanged. In the deaf ear electrostimulation of the cochlear nerve was performed using an ear canal electrode. At a stimulus current of 20 microA the body consistently reported hearing sensation. Click-evoked otoacoustic emission indicated good outer hair cell function. Hearing sensation at low stimulus intensities with electrostimulation indicated fairly good functions of the cochlear nerve. Considering also the results of imaging and auditory-evoked potentials, findings suggested that the deafness was due to an inner hair cell disorder.