Effects of the cannabinoid CB1 agonist ACEA on salicylate ototoxicity, hyperacusis and tinnitus in guinea pigs.

Cannabinoids have been suggested as a therapeutic target for a variety of brain disorders. Despite the presence of their receptors throughout the auditory system, little is known about how cannabinoids affect auditory function. We sought to determine whether administration of arachidonyl-2'-chloroethylamide (ACEA), a highly-selective CB1 agonist, could attenuate a variety of auditory effects caused by prior administration of salicylate, and potentially treat tinnitus. We recorded cortical resting-state activity, auditory-evoked cortical activity and auditory brainstem responses (ABRs), from chronically-implanted awake guinea pigs, before and after salicylate + ACEA. Salicylate-induced reductions in click-evoked ABR amplitudes were smaller in the presence of ACEA, suggesting that the ototoxic effects of salicylate were less severe. ACEA also abolished salicylate-induced changes in cortical alpha band (6-10 Hz) oscillatory activity. However, salicylate-induced increases in cortical evoked activity (suggestive of the presence of hyperacusis) were still present with salicylate + ACEA. ACEA administered alone did not induce significant changes in either ABR amplitudes or oscillatory activity, but did increase cortical evoked potentials. Furthermore, in two separate groups of non-implanted animals, we found no evidence that ACEA could reverse behavioural identification of salicylate- or noise-induced tinnitus. Together, these data suggest that while ACEA may be potentially otoprotective, selective CB1 agonists are not effective in diminishing the presence of tinnitus or hyperacusis.

Exposure to music and noise-induced hearing loss (NIHL) among professional pop/rock/jazz musicians.

Noise-induced hearing loss (NIHL) has been extensively studied in industrial work environments. With the advent of new technologies, loud music has been increasingly affecting listeners outside of the industrial setting. Most research on the effects of music and hearing loss has focused on classical musicians. The purpose of the current study was to examine the relationship between the amount of experience a professional pop/rock/jazz musician has and objective and subjective variables of the musician's hearing loss. This study also examined professional pop/rock/jazz musicians' use of hearing protection devices in relation to the extent of their exposure to amplified music. Forty-four pop/rock/jazz musicians were interviewed using the Pop/Rock/Jazz Musician's Questionnaire (PRJMQ) in order to obtain self-reported symptoms of tinnitus and hyperacusis. Forty-two of the subjects were also tested for air-conduction hearing thresholds in the frequency range of 1-8 kHz. Results show that the extent of professional pop/rock/jazz musicians' exposure to amplified music was related to both objective and subjective variables of hearing loss: Greater musical experience was positively linked to higher hearing thresholds in the frequency range of 3-6 kHz and to the subjective symptom of tinnitus. Weekly hours playing were found to have a greater effect on hearing loss in comparison to years playing. Use of hearing protection was not linked to the extent of exposure to amplified music. It is recommended that further research be conducted with a larger sample, in order to gain a greater understanding of the detrimental effects of hours playing versus years playing.

Importancia de la salud auditiva / Importance of hearing health

Se realiza un estudio sobre la exposición al ruido, sus efectos nocivos y la situación actual de lesiones auditivas en la juventud por el empleo excesivo de reproductores, así como exposición a niveles altos de ruido en discotecas. Se informa de la posibilidad de lesión auditiva en los músicos, técnicos de sonido y disk jockeys. Conscientes de esta problemática la Fundación Pedro Salesa Cabo está realizando un estudio conjuntamente con la Mutua Intercomarcal y la sociedad de prevención Prevint para el estudio de este problema y sus posibles soluciones. Este estudio «Impacto sonoro de la música en sus intérpretes y técnicos» comporta la realización de diversas pruebas auditivas en las personas afectadas (AU)

A study is made on the exposure to noise, on its harmful effects and the current situation on hearing problems in young people due to the excessive use of music players and to the exposure to high levels of noise in discotheques. Information is provided about possible hearing damage in musicians, sound technicians, and disk jockeys. The Pedro Salesa Cabo Foundation is aware of this problem and is conducting an extensive study, together with Mutua Intercomarcal and the society Prevint, to evaluate the problem and its possible solutions. This study "Impacto sonoro de la música en sus intérpretes y técnicos" is supported by different audiological tests in the people affected (AU)

[Hearing disorders and rock music]. / Høreskader og rockmusik.

Only few studies have investigated the frequency of hearing disorders in rock musicians. Performing rock music is apparently associated with a hearing loss in a fraction of musicians. Tinnitus and hyperacusis are more common among rock musicians than among the background population. It seems as if some sort of resistance against further hearing loss is developed over time. The use of ear protection devices have not been studied systematically but appears to be associated with diminished hearing loss.

Reduced parietal and visual cortical activation during global processing in Williams syndrome.

Several lines of investigation suggest that individuals with Williams syndrome (WS), a neurodevelopmental disorder of well-characterized genetic etiology, have selective impairments in integrating local image elements into global configurations. We compared global processing abilities in 10 clinically and genetically diagnosed participants with WS (eight females, two males; mean age 31y 10mo [SD 9y 7mo], range 15y 5mo-48y 4mo) with a typically developed (TD) age- and sex-matched comparison group (seven females, one male; mean age 35y 2mo [SD 10y 10mo], range 24y-54y 7mo) using functional magnetic resonance imaging (fMRI). Behavioral data showed participants with WS to be significantly less accurate (p<0.042) together with a non-significant trend to be slower than the TD comparison group while performing the global processing task. fMRI data showed participants with WS to possess reduced activation in the visual and parietal cortices. Participants with WS also showed relatively normal activation in the ventral occipitotemporal cortex, but elevated activation in several posterior thalamic nuclei. These preliminary results largely confirm previous research findings and neural models implicating neurodevelopmental abnormalities in extended subcortical and cortical visual systems in WS, most notably dorsal-stream pathways.

The natural course of migraine attacks. A prospective analysis of untreated attacks compared with attacks treated with a triptan.

This study was designed to document prospectively and explore scientifically the natural course of untreated migraine attacks in detail. A new, integrated, time-intensity method for self-assessment of the intensity of symptoms was tested on 18 adult International Headache Society migraineurs who volunteered to refrain from treatment during one attack. The area under the curves (AUC) during 72 h of untreated attacks was compared with attacks treated with a triptan. Migraine attacks are heterogeneous both inter- and intra-individually. In untreated attacks, the pain can stabilize and fluctuate around a plateau with a wavelength of hours. In general, the symptoms of each separate migraine attack follow a similar temporal course, with only moderate deviations. In some cases photo- and/or phonophobia (hyperexcitability) were not experienced at all, despite severe pain and nausea. Moreover, there was sometimes no nausea despite severe pain and hyperexcitability. Vomiting does not always correlate to the intensity of nausea and is not always followed by decreased headache intensity. Treatment with a triptan usually only temporarily distorts the basic pattern of attacks. Hyperexcitability can respond before pain to treatment. These genuine findings of the classic symptoms of migraine attacks support the notion of a mutual underlying pathophysiological mechanism.

A randomized trial of frovatriptan for the intermittent prevention of menstrual migraine.

BACKGROUND: Menstrually associated migraine (MAM) is often prolonged and difficult to manage with conventional therapies. Frovatriptan is a new selective 5HT(1B/1D) receptor agonist indicated for short-term management of migraine. It has a long half-life and good tolerability. These characteristics suggest that frovatriptan may be useful for the intermittent prevention of MAM. METHODS: The study was a randomized, double-blind, placebo-controlled, three-way crossover design. Patients treated each of three perimenstrual periods (PMPs) with placebo, frovatriptan 2.5 mg QD, and frovatriptan 2.5 mg BID. The 6-day treatment started 2 days before the anticipated start of MAM headache. The primary efficacy endpoint was incidence of MAM headache during the 6-day PMP. RESULTS: The population comprised 546 women (mean age, 37.6 years). Use of frovatriptan reduced the occurrence of MAM headache. The incidence of MAM headache during the 6-day PMP was 67% for placebo, 52% for frovatriptan 2.5 mg QD, and 41% for frovatriptan 2.5 mg BID. Both frovatriptan regimens were superior to placebo (p < 0.0001), and the BID regimen was superior to the QD regimen (p < 0.001). Both frovatriptan regimens also reduced MAM severity (p < 0.0001), duration (p < 0.0001), and the use of rescue medication (p < 0.01 QD; p < 0.0001 BID) in a dose-dependent manner. The incidence and type of adverse events for both regimens were similar to placebo and consistent with those reported for short-term migraine management. CONCLUSION: Frovatriptan given prophylactically for 6 days was effective in reducing the incidence of menstrually associated migraine. More than half of patients who used frovatriptan 2.5 mg BID had no menstrually associated migraine headache during the 6-day perimenstrual period. The findings are consistent with the long duration of action and good tolerability of frovatriptan observed in short-term migraine management.

Zolmitriptan is effective and well tolerated in Japanese patients with migraine: a dose-response study.

This phase II study investigated the efficacy, tolerability and dose-response relationship of oral zolmitriptan in the treatment of a single migraine attack in Japanese patients. A bridging analysis then assessed the validity of extrapolating western clinical data to these Japanese patients. In this multicentre, randomized, double-blind, placebo-controlled study, patients received a single dose of placebo or zolmitriptan 1, 2.5 or 5 mg. The primary endpoints were 2-h headache response and the tolerability of zolmitriptan. A statistically significant dose-response relationship was observed for the 2-h headache response (P=0.003). The 2.5 mg group had significantly greater 2-h headache response than the placebo group (P=0.032). The adverse event profile was similar to that reported in western patients, and no adverse events unique to the Japanese population were observed. The bridging analysis report confirmed similar efficacy and tolerability of zolmitriptan in Japanese and western populations. In the Japanese patients, the estimated response rates were 34.3%, 45.2%, 57.7% and 66.2% for placebo, and zolmitriptan 1, 2.5 and 5 mg, respectively, while in the western population the corresponding rates were 39.9%, 49.6%, 61.2% and 71.7%. Zolmitriptan is effective and well tolerated in the acute treatment of migraine in Japanese patients. The optimal dose was 2.5 mg, although the 5 mg dose may provide further benefit for some patients. The bridging analysis supports extrapolation of data from western to Japanese patients.