Efficacy and safety of AM-111 in the treatment of acute sensorineural hearing loss: a double-blind, randomized, placebo-controlled phase II study.

OBJECTIVE: To evaluate the efficacy and safety of AM-111, a c-Jun N-terminal Kinase (JNK) ligand, in patients with acute sensorineural hearing loss (ASNHL). STUDY DESIGN: Prospective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 3, 7, 30, and 90. SETTING: Twenty-five European sites (academic tertiary referral centers, private ENT practices). PATIENTS: Approximately 210 patients aged 18 to 61 years presenting within 48 hours after acute acoustic trauma or idiopathic sudden sensorineural hearing loss with mean hearing loss of 30 dB or greater at the 3 most affected contiguous test frequencies. INTERVENTIONS: Single-dose intratympanic injection of AM-111 (0.4 or 2.0 mg/ml) or placebo; optionally, oral prednisolone if hearing improvement was less than 10 dB at Day 7. MAIN OUTCOME MEASURES: Efficacy was assessed by absolute hearing improvement (primary end point, Day 7), percentage hearing improvement, complete hearing recovery, speech discrimination improvement, and complete tinnitus remission. Safety was evaluated by the frequency of clinically relevant hearing deterioration and adverse events. RESULTS: The study failed to demonstrate a treatment benefit for the entire study population because mild-to-moderate ASNHL cases showed unexpectedly strong spontaneous recovery. In severe-to-profound ASNHL patients (threshold ≥60 dB), AM-111 0.4 mg/ml showed statistically significant, clinically relevant, and persistent improvements in hearing and speech discrimination and higher tinnitus remission compared with placebo. The study drug and the intratympanic injections were well tolerated. CONCLUSION: The study established proof of concept for AM-111 in the treatment of severe-to-profound ASNHL. Control for spontaneous hearing recovery is essential for ASNHL studies.

[Meningitis and chosen complications of neonatal period in preterm neonates born to single or multiple pregnancies]. / Neuroinfekcje a wybrane powiklania okresu noworodkowego u dzieci urodzonych przedwczesnie z ciaz pojedynczych i wieloplodowych.

UNLABELLED: The aim of this study was to determine the relationship between meningitis and neonatal period of complications such as massive intraventricular hemorrhage and into brain tissue, hypoxic-ischemic white matter injury retinopathy of prematurity 3-5 degrees and deafness in infants born prematurely from single and multiple pregnancies. MATERIAL: The retrospective study covered 460 preterm infants born to single pregnancies and 280 infants born prematurely with multiple pregnancies, hospitalized in the Clinic of Neonatology PUM in the years: 2005-2008. RESULTS: There were no statistically significant differences between the frequency of occurrence: peri/intraventricular hemorrhages (IVH) III degrees and IV degrees, hypoxic-ischemic injury in white matter, retinopathy of prematurity 3-5 degrees and hearing loss in newborns of both groups. Meningitis was diagnosed in 35 (7.92%) newborns from singleton pregnancy and in 9 (3.25%) with a multiple pregnancy. It was found that the risk of meningitis was significantly greater in infants with body weight less than 1000 grams (OR 4.18), and born under 28 weeks of gestation (OR = 5.07), regardless of group affiliation. We found a statistically significant correlation between the occurrence of meningitis and neonatal complications such as IVH III degrees and IV degrees (OR-5, 56), hypoxic-ischemic white matter injury (OR - 18.93) and retinopathy of prematurity (7.45) in newborns with both single and multiple pregnancies. There was no effect of meningitis on the incidence of hearing loss. CONCLUSION: There exists a significant association between the occurrence of meningitis and some neonatal complications such as massive intraventricular hemorrhage, hypoxic-ischemic changes in white matter of the brain and retinopathy of prematurity 3-5 degrees, leading to disturbances in the further development of the prematurely born child. The incidence of meningitis in newborn infants is inversely proportional to the duration of pregnancy.

[Diagnostic problems of rare cerebellopontine angle tumors]. / Problemy diagnostyczne w rozpoznawaniu rzadkich guzów kata mostowo-mózdzkowego.

UNLABELLED: Astrocytoma (neuroepithelial tumor) determine about 25% all the cerebroma but their original location in cerebellopontine angle is seldom. In case of this kind of tumors in this place, the symptoms can be non-characteristic and similar to these, which appear in the acoustic neurinoma. The most important in case of this diagnosis is both that this tumors can infiltrate of the brain tissues and the fact that they can transformate toward the anaplastic astrocytoma or glioblastoma multiforme (very malignant tumors). MATERIAL AND METHODS: [corrected] A rare case of astrocytoma presenting as a cerebellopontine angle tumor is discussed. The special characteristics of this tumor and unusual clinical course are disscused. CONCLUSION: The early diagnosis of the astrocytoma increases the patient's chance on convalescence and limits extension of the operation, and consequently of the neurological complication.

[Acute ear trauma caused by failure of mobile phone/cellular phone]. / Ostry uraz akustyczny i termiczny ucha spowodowany awaria telefonu komórkowego.

The case of acute acoustic and burn ear trauma caused by mobile phone failure is presented. A woman aged 24 after dialling a phone number and putting a phone into the ear heard a sound of high frequency and intensity. At the same time she felt a pain and heat and there was also a smoke from the phone. With otoscopic examination a burn of external acoustic duct (I0) and sensitive hearing loss (examination made with tuning forks) were stated. The patient did not agree to stay in hospital and she was administered prednizone, trimetazidin and xantylol nicotinate. Audiometric examination, which was made on another day, showed hearing loss of 30 dB for frequency 4000Hz. After 2 days she started to hear a sound like a sea noise in her right ear. In the control examination, made 2 weeks after injury, no abnormalities in audiogram were stated but the patient steal heard ear noise. She continued to take trimetazidin and betahistin and after one month all symptoms of ear injury relieved. Patient is still under control of otolaryngologist. Unfortunately our efforts to explain the cause of such accident from phone producer were ineffective. Described case proves that mobile phone failure can be a cause of acute ear injury.

Noncystic white matter injury--a case report.

Magnetic resonance imaging (MRI) of the brain in preterm infants at term-equivalent age demonstrated that apart from cystic periventricular leukomalacia (PVL), noncystic white matter injury may take place, detected as diffuse excessive high signal intensity (DEHSI) in the white matter on T2-weighted imaging. Magnetic resonance imaging of the brain is conducted in few neonatal intensive care units. Consequently, the literature on the subject lacks descriptions of sequelae of noncystic white matter injury in premature newborns with very low birth weight (VLBW). We present the results of a three-year long observation of a child born at the 27th week of pregnancy diagnosed with DEHSI. The boy exhibited cerebral palsy, hyperexcitability and hypoacusis. In the authors' opinion, noncystic white matter injury may not just be one of the reasons for cognitive/behavioral deficits--it may also be responsible for some cases of cerebral palsy in premature infants.

[Application of conscious sedation in infants undergoing the auditory brainstem responses (ABR) examination]. / Zastosowanie sedacji plytkiej u niemowlat w przygotowaniu do badania potencjalów sluchowych z pnia mózgu (ABR).

Results of ABR examination in infants undergone the hearing screening examinations were presented. Since February 2004 the group of 184 children were examined. In 29 of them (15.8%) there was a need of further hearing examination using evoked auditory brainstem responses. In 20 of them the examination was done in sleep induced by 6% chloral hydrate enema. The process of sleep was normal and no disturbances of breathing or circulatory systems were observed. The obtained responses from brainstem were not interfered by any artifacts and basic waves were legible and easy for interpretation. Correct results of the ABR examination were obtained in 21/29 (72%) children, while in 7/28 (24%) various degree of hearing losses were detected. Those children were referred for hearing rehabilitation to the Third Degree of Reference Center. It was emphasized in the study that results of ABR examination after conscious sedation induced by 6% chloral hydrate enema accounted the suggestion for its wider use in other clinical and hospital center.