Ilmari Pyykkö - Academia.edu (original) (raw)

Papers by Ilmari Pyykkö

Advances in Oto-Rhino-Laryngology, 2019

International journal of occupational safety and ergonomics : JOSE, 2009

Directive 2003/10/EC sets the requirement for evaluating the effect of noise on accident risk. Ac... more Directive 2003/10/EC sets the requirement for evaluating the effect of noise on accident risk. Accident risk is elevated for workers with a hearing handicap because of their reduced speech intelligibility and reduced capability to perceive the direction of incoming sound. An audiogram is not a good method for the evaluation of these functions. To reduce accident risk, organisational and personal solutions are needed. For both methods, efficiency must be evaluated through proper risk assessment. Because practical guidelines are not available, this paper presents principles for accident risk evaluation techniques.

Noise & health, 2000

We have analysed the association of noise-induced hearing loss with various risk factors among 68... more We have analysed the association of noise-induced hearing loss with various risk factors among 685 workers in forest, shipyard, and paper mills. Occupational histories, health, environmental factors, and noise exposures of each worker were retrieved from the database of NoiseScan, our expert program on hearing. The mean hearing level at 4 kHz was 21.5 dB +/- 20.3 dB HL. It correlated significantly with age, noise emission level and noise exposure level. However, these factors could only explain about 2 dB HL of the variation in hearing level. Impulse noise in the shipyard work caused increase in hearing level of 12 dB HL at 4 kHz when compared to steady state noise exposure of forest work. Hearing level correlated with serum cholesterol levels, use of analgesics, blood pressure and smoking. An elevated cholesterol level increased hearing loss in both the high- and low-exposure groups. The use of analgesics did not increase a permanent threshold shift in the low-exposure group, but d...

Acta Oto-Laryngologica, 2015

Conclusions: The present experimental setup of high spatial resolution cone-beam computed tomogra... more Conclusions: The present experimental setup of high spatial resolution cone-beam computed tomography (CBCT) showed advantages of demonstrating the critical landmarks of the cochlea in identifying the position of intracochlear electrode contacts and has the potential for clinical application in cochlear implant (CI) surgery. Objective: To evaluate a newly developed CBCT system in defining CI electrode array in human temporal bone and cochlear morphological variation. Methods: Standard electrode, flexible tip electrode (Flex28), and an experimental electrode array with 36 contacts from MED-EL were implanted into the cochleae of six human temporal bones through an atraumatic round window membrane insertion. The cochleae were imaged with 900 frames using an experimental setup based on a CBCT scanner installed with Superior SXR 130-15-0.5 X-ray tube in combination with filtration of copper and aluminum. Results: In all temporal bones, the landmarks of the cochlea, modiolus, osseous spiral lamina, round window niche, and stapes were demonstrated at an average level of 3.4-4.5. The contacts of electrode arrays were clearly shown to locate in the scala tympani. There was a linear correlation between the 'A' value and cochlea height, and between the A value and actual electrode insertion length for the first 360 insertion depth.

International journal of pharmaceutics, Jan 14, 2011

Nanoparticle-mediated drug delivery represents the future in terms of treating inner ear diseases... more Nanoparticle-mediated drug delivery represents the future in terms of treating inner ear diseases. Lipid core nanocapsules (LNCs), 50 nm in size, were shown to pass though the round window membrane (RWM) and reached the spiral ganglion cells and nerve fibers, among other cell types in the inner ear. The present study aimed to evaluate the toxicity of the LNCs in vitro and in vivo, utilizing intact round window membrane delivery in rats. The primary cochlear cells and mouse fibroblast cells treated with LNCs displayed dosage dependant toxicity. In vivo study showed that administration of LNCs did not cause hearing loss, nanoparticle application-related cell death, or morphological changes in the inner ear, at up to 28 days of observation. The cochlear neural elements, such as synaptophysin, ribbon synapses, and S-100, were not affected by the administration of LNCs. However, expression of neurofilament-200 decreased in SGCs and in cochlear nerve in osseous spiral lamina canal after L...

Journal of nanobiotechnology, Jan 27, 2015

BackgroundSilver nanoparticles (Ag NPs) displayed strong activities in anti-bacterial, anti-viral... more BackgroundSilver nanoparticles (Ag NPs) displayed strong activities in anti-bacterial, anti-viral, and anti-fungal studies and were reportedly efficient in treating otitis media. Information on distribution of AgNPs in different compartments of the ear is lacking.ObjectiveTo detect distribution of Ag NPs in the middle and inner ear and transportation pathways after transtympanic injection.MethodsContrast effect of Ag NPs in the micro CT imaging was assessed in a phantom. AgNPs at various concentrations (1.85 mM, 37.1 mM, and 370.7 mM) were administered to rat middle ear using transtympanic injection and cadaver heads were imaged using micro CT at several time points.ResultsThe lowest concentration of Ag NPs that could be visualized using micro CT was 37.1 mM. No difference was observed between the solvents, deionized H2O and saline. Ag NPs at 37.1 mM were visible in the middle ear on 7 d post-administration. Ag NPs at 370.7 mM generated signals in the middle ear, ossicular chain, ro...

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 2007

The sensorineural hearing loss (HL) after middle ear surgery has been explained by the noise gene... more The sensorineural hearing loss (HL) after middle ear surgery has been explained by the noise generated by drilling, without considering the vibration generated by the burr. The role of temporal bone vibration in the etiology of the HL was evaluated. An electromagnetic shaker was used to vibrate the bony external ear canal of guinea pigs at different frequencies ranging from 32 to 1,000 Hz and at intensities ranging from 4.2 to 18.8 m/s for 15 minutes. The hearing threshold was measured with auditory evoked responses. A total of 30 animals were tested. After vibration, 60% of the guinea pigs developed a threshold shift (TS) exceeding 10 dB at two frequencies, with average TS of 8.8 dB across all frequencies and animals. The exposure to vibration at higher frequencies (range, 500-1,000 Hz) produced stronger TS than did the exposure to lower frequencies (range, 32-250 Hz). The vibration-induced TS showed prominent recovery so that after 7 days, TS was 2.4 dB on average and 27 of 30 ani...

Scandinavian Audiology, 1996

The noise generated by stimulating coils may jeopardize the hearing of the patients as well as th... more The noise generated by stimulating coils may jeopardize the hearing of the patients as well as the hearing of the examiner. To evaluate the potential risk caused by the impulse noise of stimulating coils, we examined the A-weighted peak sound pressure levels from five different types of magnetic stimulator coils. At a distance of 10 cm, with 100% stimulation intensity, the coils with Dantec and Magstim stimulators created maximum peak sound pressure levels of 110 dB. Correspondingly, Cadwell MES-10 created maximum peak sound pressure levels of 132 dB. The decrease in the peak levels followed the distance rule quite closely. At a distance of 40 cm, the decrease in peak level was on average 14 dB (range -1-(+)1 dB). Based on American Conference of Governmental Industrial Hygienists (ACGIH) threshold limits of impact noise, the permitted maximum daily number of magnetic stimuli would be 1000 to 10,000. The permitted number of daily stimuli may be difficult to exceed in clinical practice. We consider the risk as small for the patients that are being examined and the operator using magnetic stimulation. The potential risk can be further diminished by even very light weighted hearing protectors providing proper attenuation to the coil impulses.

The Journal of Steroid Biochemistry and Molecular Biology, 2009

The vitamin D endocrine system is essential for calcium and bone homeostasis. Vitamin D deficits ... more The vitamin D endocrine system is essential for calcium and bone homeostasis. Vitamin D deficits are associated with muscle weakness and osteoporosis, whereas vitamin D supplementation may improve muscle function, body sway and frequency of falls, growth and mineral homeostasis of bones. The loss of muscle strength and mass, as well as deficits in bone formation, lead to poor balance. Poor balance is one of the main causes of falls, and may lead to dangerous injuries. Here we examine balance functions in vitamin D receptor deficient (VDR−/−) mice, an animal model of vitamin D-dependent rickets type II, and in 1␣-hydroxylase deficient (1␣-OHase−/−) mice, an animal model of pseudovitamin D-deficiency rickets. Recently developed methods (tilting box, rotating tube test), swim test, and modified accelerating rotarod protocol were used to examine whether the absence of functional VDR, or the lack of a key vitamin D-activating enzyme, could lead to mouse vestibular dysfunctions. Overall, VDR−/− mice, but not 1␣-OHase−/− mice, showed shorter latency to fall from the rotarod, smaller fall angle in the tilting box test, and aberrant poor swimming. These data suggest that VDR deficiency in mice is associated with decreased balance function, and may be relevant to poorer balance/posture control in humans with low levels of vitamin D.

Proceedings of the National Academy of Sciences, 2002

A primary cause of deafness is damage of receptor cells in the inner ear. Clinically, it has been... more A primary cause of deafness is damage of receptor cells in the inner ear. Clinically, it has been demonstrated that effective functionality can be provided by electrical stimulation of the auditory nerve, thus bypassing damaged receptor cells. However, subsequent to sensory cell loss there is a secondary degeneration of the afferent nerve fibers, resulting in reduced effectiveness of such cochlear prostheses. The effects of neurotrophic factors were tested in a guinea pig cochlear prosthesis model. After chemical deafening to mimic the clinical situation, the neurotrophic factors brain-derived neurotrophic factor and an analogue of ciliary neurotrophic factor were infused directly into the cochlea of the inner ear for 26 days by using an osmotic pump system. An electrode introduced into the cochlea was used to elicit auditory responses just as in patients implanted with cochlear prostheses. Intervention with brain-derived neurotrophic factor and the ciliary neurotrophic factor analo...

Otology & Neurotology, 2008

To assess the biocompatibility of different biopolymers with cochlea implant. Six bioabsorbable p... more To assess the biocompatibility of different biopolymers with cochlea implant. Six bioabsorbable polymers and biostable silicone were used for testing histologic reactions in the cochlea of the rat. The samples were prepared from three 50/50 poly(DL-lactide-co-glycolide) PDLLGA having different inherent viscosity (IV) values and 75/25 poly(DL-lactide-co-epsilon-caprolactone) P(DLLA/CL), poly-epsilon-caprolactone PCL, silicone, and chitosan by extruding the biomaterial as a rod using melt molding (for 50/50 PDLLGAs and 75/25 P(DLLA/CL) and PCL), blending (for silicone), and solving (for chitosan). The rods were cut into samples of diameter of 0.5 mm and length of 2 mm. All the samples were packed and sterilized by gamma irradiation (18 kGy, less than 42 degrees C). Twenty-two male and female Sprague-Dawley rats were used in the study. Four months after the implantation, the animals were killed for histologic observation. Chitosan does not degrade in the cochlea 4 months after implantation and, therefore, stimulates very weak inflammatory reaction. The 50/50 PDLLGA (IV, 0.83 dL/g) degrades in the cochlea 4 months after implantation and does not stimulate inflammatory reaction. The 50/50 PDLLGA (IV, 0.41 dL/g; IV, 0.37 dL/g), 75/25 P(DLLA/CL), PCL, and silicone might induce strong inflammatory reaction in the cochlea. Different degradation property of biomaterials in the cochlea indicates diverse drug releasing time in a controlled way. Chitosan is suitable for long-lasting drug delivery, whereas 50/50 PDLLGA (IV, 0.83 dL/g) favors quicker releasing. Both chitosan and 50/50 PDLLGA (IV, 0.83 dL/g) are ideal materials for cochlear drug delivery.

Otolaryngologic Clinics of North America, 2010

Recent magnetic resonance imaging (MRI) techniques have made it possible to examine the compartme... more Recent magnetic resonance imaging (MRI) techniques have made it possible to examine the compartments of the cochlea using gadolidium-chelate (GdC) as a contrast agent. As GdC loads into the perilymph space without entering the endolymph in healthy inner ears, the technique provides possibilities to visualize the different cochlear compartments and evaluate the integrity of the inner ear barriers. This critical review presents the recent advancements in the inner ear MRI technology, contrast agent application and the correlated ototoxicity study, and the uptake dynamics of GdC in the inner ear. GdC causes inflammation of the mucosa of the middle ear, but there are no reports or evidence of toxicity-related changes in vivo either in animals or in humans. Intravenously administered GdC reached the guinea pig cochlea about 10 minutes after administration and loaded the scala tympani and scala vestibuli with the peak at 60 minutes. However, the perilymphatic loading peak was 80 to 100 minutes in mice after intravenous administration of GdC. In healthy animals the scala media did not load GdC. In mice in which GdC was administered topically onto the round window, loading of the cochlea peaked at 4 hours, at which time it reached the apex. The initial portions of the organ to be filled were the basal turn of the cochlea and vestibule. In animal models with endolymphatic hydrops (EH), bulging of the Reissner's membrane was observed as deficit of GdC in the scala vestibuli. Histologically the degree of bulging correlated with the MR images. In animals with immune reaction-induced EH, MRI showed that EH could be limited to restricted regions of the inner ear, and in the same inner ear both EH and leakage of GdC into the scala media were visualized. More than 100 inner ear MRI scans have been performed to date in humans. Loading of GdC followed the pattern seen in animals, but the time frame was different. In intravenous delivery of double-dose GdC, the inner ear compartments were visualized after 4 hours. The uptake pattern of GdC in the perilymph of humans between 2 hours and 7 hours after local delivery needs to be clarified. In almost all patients with probable or suspected Ménière's disease, EH was verified. Specific algorithms with a 12-pole coil using fluid attenuation inversion recovery sequences are recommended for initial imaging in humans.

Noise and Health, 2011

This study intended to evaluate classical musicians&a... more This study intended to evaluate classical musicians' risk of hearing loss. We studied 63 musicians from four Helsinki classical orchestras. We measured their hearing loss with an audiometer, found their prior amount of exposure to sound and some individual susceptibility factors with a questionnaire, measured their present sound exposure with dosimeters, and tested their blood pressure and cholesterol levels, then compared their hearing loss to ISO 1999-1990's predictions. The musicians' hearing loss distribution corresponded to that of the general population, but highly exposed musicians had greater hearing loss at frequencies over 3 kHz than less-exposed ones. Their individual susceptibility factors were low. Music deteriorates hearing, but by less than what ISO 1999-1990 predicted. The low number of individual susceptibility factors explained the difference, but only reduced hearing loss and not the prevalence of tinnitus.

Nanomedicine, 2014

Aim: To validate a novel sustained delivery system of liposome nanocarriers for inner-ear therapy... more Aim: To validate a novel sustained delivery system of liposome nanocarriers for inner-ear therapy and to investigate the transport pathway for their delivery. Materials & methods: Liposome nanocarriers containing gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (LPS+Gd-DOTA) were developed for MRI tracking the in vitro release profile and for in vivo uptake studies. Results: Encapsulating Gd-DOTA did not modify the liposomes. The LPS+Gd-DOTA nanocarriers were slowly released from a miniature osmotic pump. The LPS+Gd-DOTA moved along the ossicular chain toward the oval window after an epitympanic injection, whereas they traveled directly to the round window after a mesotympanic injection. However, the round window membrane was the major pathway for the LPS+Gd-DOTA to enter the inner ear. LPS+Gd-DOTA were visualized on both sides of the cochlea within 6 days of in vivo delivery via the osmotic pump. Discussion: The novel sustained inner-ear delivery system induced liposome nanocar...

Journal of Neuroscience Research, 2009

The inward-rectifier K 1 channel Kir4.1 is responsible for maintaining cochlear homeostasis and r... more The inward-rectifier K 1 channel Kir4.1 is responsible for maintaining cochlear homeostasis and restoring neural excitability. The large-conductance calcium-activated K 1 channel (BK Ca) plays a key role in phase locking signals in the mammalian inner ear. To evaluate the influence of mitochondrial dysfunction on the expression and subcellular localization of these channels, 3-nitropropionic acid (3-NP) was administered to rat round window membranes for 30 min. Auditory brainstem response was measured both before and 2 hr after 3-NP administration. Immunofluorescent confocal microscopy was used to measure the expression and subcellular localization of Kir4.1 and BK Ca. Alexa Fluor 568-labeled bovine serum albumin (BSA) was applied to round window membranes as a tracer to explore the cochlear distribution of drug delivery and was detected in the lateral wall, spiral ganglion, cochlear nerve, and organ of Corti. Hearing loss of 23 (64.4 SE) and 58 (66.7 SE) dB developed in rats treated with 0.3 and 0.5 mol/liter of 3-NP, respectively. BK Ca was visualized in the cellular membrane and cytoplasm in the upper and middle region of inner hair cells, and it was not affected by 3-NP. Kir4.1 was detected in intermediate cells of the stria, Deiter's cells, and spiral ganglion satellite cells. Kir4.1 failed to reach the perineural cytoplasm of the satellite cells after 3-NP treatment. The results of this study suggest that mitochondrial dysfunction disrupts trafficking of Kir4.1 in spiral ganglion satellite cells. V

International Archives of Occupational and Environmental Health, 2008

Officially 10-26 cases of vibration-induced white fingers (VWF) have been reported annually in Fi... more Officially 10-26 cases of vibration-induced white fingers (VWF) have been reported annually in Finland. It has been suggested that the numbers are underestimated. The purpose of the present study was to estimate the cumulative exposure to hand-arm vibration (HAV) and the prevalence of clinically diagnosed cases of VWF and carpal tunnel syndrome (CTS) in a population of Finnish metal workers and to determine the symptoms and clinical tests that would best predict the diagnosis. A questionnaire on vibration exposure at the workplace and symptoms of the upper extremities was sent to a sample (n = 530) of members of the local Metalworkers Union. Those who reported finger blanching, numbness or tingling of the fingers or symptoms of CTS were invited to take part in clinical examinations. Their cumulative lifelong exposure to HAV was evaluated. Those whose symptoms referred to VWF or CTS were given a cold provocation test with the measurement of finger systolic blood pressure and electroneuromyography of the upper arms. Altogether 285 metal workers (54%) responded to the questionnaire, and 24 new cases of VWF (8.4%) and 12 cases of CTS (4.2%) were diagnosed. In the group of VWF patients, seven workers had both VWF and CTS. All of the workers diagnosed as having VWF also had numbness or tingling in their fingers. Consequently, questions concerning numbness and tingling, a two-point discrimination test, Phalen's test, and Tinell's test had a high predicting value for VWF. The exposure time of the VWF cases did not differ significantly from that of the study group as whole, but the cumulative exposure index was significantly higher. The results suggest that VWF is underdiagnosed in Finland. In screening for the health effects of HAV, sensorineural symptoms of hands should be carefully inquired about and examined in patients complaining of white fingers. More education on the recognition and evaluation of HAV exposure and its health effects is needed.

International Archives of Occupational and Environmental Health, 2006

Hand-arm vibration syndrome (HAVS) consists of vascular and neurological component. Musculoskelet... more Hand-arm vibration syndrome (HAVS) consists of vascular and neurological component. Musculoskeletal component has not been delineated yet. In the present follow-up study, we evaluated the prevalence of HAVS and the cumulative exposure to vibration among a cohort of forestry workers. Special interest was given to numbness and musculoskeletal disorders of upper extremity and neck in forestry workers. A follow-up study starting from 1976 was conducted among forestry workers in Suomussalmi in Finland. Total exposure of hand-arm vibration was recorded during 11 cross-sectional surveys. The last study was carried out in 1995. The lifetime dose of vibration energy was calculated. A cohort of 52 forest workers participated to all 11 cross-sectional surveys 1976-1995. HAVS and musculoskeletal disorders were evaluated. The prevalence of active vibration white finger (VWF) decreased from 13 to 4% in the cross-sectional study. In the cohort VWF decreased from 17 to 8% and numbness increased from 23 to 40%. Rotator cuff syndrome (P=0.034) and epicondylitis (P=0.004) associated with numbness. Regional neck pain was diagnosed in 38% of workers and associated with low back pain. In modeling VWF, the lifelong vibration energy (OR 1.03, CI 1.01-1.05), and smoking (OR 7.36, CI 1.07-50.76) were significant. Numbness was modeled by pain in upper extremities (OR 12.43, CI 2.42-63.80) and neck pain (5.97, CI 1.25-28.39), not by lifelong vibration energy. Right rotator cuff syndrome was modeled by age (OR 2.58, CI 1.04-6.41) and lifelong vibration energy (OR 1.04, CI 1.00-1.07). The prevalence of VWF constantly decreased. Numbness did not follow the vibration exposure profile. Numbness also associated with upper extremity musculoskeletal disorders. Hand-arm vibration associated with the right rotator cuff syndrome in forestry workers.

European Archives of Oto-Rhino-Laryngology, 2013

To elucidate the communication between the middle and inner ear, and the fluid dynamics of the in... more To elucidate the communication between the middle and inner ear, and the fluid dynamics of the inner ear with the perilymphatic fistula (PLF) of the round window membrane (RWM). The PLF of the RWM was created in nine guinea pigs. Gadolinium diethylenetriamine pentaacetic acid bismethylamide (Gd-DTPA-BMA) was delivered into the middle ear and followed in the inner ear using a 4.7 Tesla MRI. Pressure was delivered to the external ear canal of PLF ear in an attempt to enhance the inner ear uptake of Gd-DTPA-BMA. The immediate loading of Gd-DTPA-BMA in the scala tympani of the basal turn was ablated by the outflow of perilymph through the leaking RWM while the oval window passage for Gd-DTPA-BMA was enhanced. There was more Gd-DTPA-BMA distribution in the scala tympani than in the scala vestibuli in the second turn of the PLF cochlea (within 20 min). Signal in the vestibulum and scala vestibuli of the basal turn and rest part of PLF cochlea was greater than that of the control cochlea with intact RWM within 30 min. Pressure applied to the external ear canal tended to enhance the loading of Gd-DTPA-BMA in the perilymphatic scalae of the PLF cochlea. The enhanced oval window passage of Gd-DTPA-BMA was proven by the distorted distribution in the inner ear with PLF. The radial communication of cochlear perilymph was supported by the Gd-DTPA-BMA gradient among the perilymphatic scalae. Applying positive pressure to the external ear canal caused backflow of perilymph into the cochlea which has a potential of transmitting microbes from the middle ear into the inner ear.

Advances in Oto-Rhino-Laryngology, 2019

International journal of occupational safety and ergonomics : JOSE, 2009

Directive 2003/10/EC sets the requirement for evaluating the effect of noise on accident risk. Ac... more Directive 2003/10/EC sets the requirement for evaluating the effect of noise on accident risk. Accident risk is elevated for workers with a hearing handicap because of their reduced speech intelligibility and reduced capability to perceive the direction of incoming sound. An audiogram is not a good method for the evaluation of these functions. To reduce accident risk, organisational and personal solutions are needed. For both methods, efficiency must be evaluated through proper risk assessment. Because practical guidelines are not available, this paper presents principles for accident risk evaluation techniques.

Noise & health, 2000

We have analysed the association of noise-induced hearing loss with various risk factors among 68... more We have analysed the association of noise-induced hearing loss with various risk factors among 685 workers in forest, shipyard, and paper mills. Occupational histories, health, environmental factors, and noise exposures of each worker were retrieved from the database of NoiseScan, our expert program on hearing. The mean hearing level at 4 kHz was 21.5 dB +/- 20.3 dB HL. It correlated significantly with age, noise emission level and noise exposure level. However, these factors could only explain about 2 dB HL of the variation in hearing level. Impulse noise in the shipyard work caused increase in hearing level of 12 dB HL at 4 kHz when compared to steady state noise exposure of forest work. Hearing level correlated with serum cholesterol levels, use of analgesics, blood pressure and smoking. An elevated cholesterol level increased hearing loss in both the high- and low-exposure groups. The use of analgesics did not increase a permanent threshold shift in the low-exposure group, but d...

Acta Oto-Laryngologica, 2015

Conclusions: The present experimental setup of high spatial resolution cone-beam computed tomogra... more Conclusions: The present experimental setup of high spatial resolution cone-beam computed tomography (CBCT) showed advantages of demonstrating the critical landmarks of the cochlea in identifying the position of intracochlear electrode contacts and has the potential for clinical application in cochlear implant (CI) surgery. Objective: To evaluate a newly developed CBCT system in defining CI electrode array in human temporal bone and cochlear morphological variation. Methods: Standard electrode, flexible tip electrode (Flex28), and an experimental electrode array with 36 contacts from MED-EL were implanted into the cochleae of six human temporal bones through an atraumatic round window membrane insertion. The cochleae were imaged with 900 frames using an experimental setup based on a CBCT scanner installed with Superior SXR 130-15-0.5 X-ray tube in combination with filtration of copper and aluminum. Results: In all temporal bones, the landmarks of the cochlea, modiolus, osseous spiral lamina, round window niche, and stapes were demonstrated at an average level of 3.4-4.5. The contacts of electrode arrays were clearly shown to locate in the scala tympani. There was a linear correlation between the 'A' value and cochlea height, and between the A value and actual electrode insertion length for the first 360 insertion depth.

International journal of pharmaceutics, Jan 14, 2011

Nanoparticle-mediated drug delivery represents the future in terms of treating inner ear diseases... more Nanoparticle-mediated drug delivery represents the future in terms of treating inner ear diseases. Lipid core nanocapsules (LNCs), 50 nm in size, were shown to pass though the round window membrane (RWM) and reached the spiral ganglion cells and nerve fibers, among other cell types in the inner ear. The present study aimed to evaluate the toxicity of the LNCs in vitro and in vivo, utilizing intact round window membrane delivery in rats. The primary cochlear cells and mouse fibroblast cells treated with LNCs displayed dosage dependant toxicity. In vivo study showed that administration of LNCs did not cause hearing loss, nanoparticle application-related cell death, or morphological changes in the inner ear, at up to 28 days of observation. The cochlear neural elements, such as synaptophysin, ribbon synapses, and S-100, were not affected by the administration of LNCs. However, expression of neurofilament-200 decreased in SGCs and in cochlear nerve in osseous spiral lamina canal after L...

Journal of nanobiotechnology, Jan 27, 2015

BackgroundSilver nanoparticles (Ag NPs) displayed strong activities in anti-bacterial, anti-viral... more BackgroundSilver nanoparticles (Ag NPs) displayed strong activities in anti-bacterial, anti-viral, and anti-fungal studies and were reportedly efficient in treating otitis media. Information on distribution of AgNPs in different compartments of the ear is lacking.ObjectiveTo detect distribution of Ag NPs in the middle and inner ear and transportation pathways after transtympanic injection.MethodsContrast effect of Ag NPs in the micro CT imaging was assessed in a phantom. AgNPs at various concentrations (1.85 mM, 37.1 mM, and 370.7 mM) were administered to rat middle ear using transtympanic injection and cadaver heads were imaged using micro CT at several time points.ResultsThe lowest concentration of Ag NPs that could be visualized using micro CT was 37.1 mM. No difference was observed between the solvents, deionized H2O and saline. Ag NPs at 37.1 mM were visible in the middle ear on 7 d post-administration. Ag NPs at 370.7 mM generated signals in the middle ear, ossicular chain, ro...

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 2007

The sensorineural hearing loss (HL) after middle ear surgery has been explained by the noise gene... more The sensorineural hearing loss (HL) after middle ear surgery has been explained by the noise generated by drilling, without considering the vibration generated by the burr. The role of temporal bone vibration in the etiology of the HL was evaluated. An electromagnetic shaker was used to vibrate the bony external ear canal of guinea pigs at different frequencies ranging from 32 to 1,000 Hz and at intensities ranging from 4.2 to 18.8 m/s for 15 minutes. The hearing threshold was measured with auditory evoked responses. A total of 30 animals were tested. After vibration, 60% of the guinea pigs developed a threshold shift (TS) exceeding 10 dB at two frequencies, with average TS of 8.8 dB across all frequencies and animals. The exposure to vibration at higher frequencies (range, 500-1,000 Hz) produced stronger TS than did the exposure to lower frequencies (range, 32-250 Hz). The vibration-induced TS showed prominent recovery so that after 7 days, TS was 2.4 dB on average and 27 of 30 ani...

Scandinavian Audiology, 1996

The noise generated by stimulating coils may jeopardize the hearing of the patients as well as th... more The noise generated by stimulating coils may jeopardize the hearing of the patients as well as the hearing of the examiner. To evaluate the potential risk caused by the impulse noise of stimulating coils, we examined the A-weighted peak sound pressure levels from five different types of magnetic stimulator coils. At a distance of 10 cm, with 100% stimulation intensity, the coils with Dantec and Magstim stimulators created maximum peak sound pressure levels of 110 dB. Correspondingly, Cadwell MES-10 created maximum peak sound pressure levels of 132 dB. The decrease in the peak levels followed the distance rule quite closely. At a distance of 40 cm, the decrease in peak level was on average 14 dB (range -1-(+)1 dB). Based on American Conference of Governmental Industrial Hygienists (ACGIH) threshold limits of impact noise, the permitted maximum daily number of magnetic stimuli would be 1000 to 10,000. The permitted number of daily stimuli may be difficult to exceed in clinical practice. We consider the risk as small for the patients that are being examined and the operator using magnetic stimulation. The potential risk can be further diminished by even very light weighted hearing protectors providing proper attenuation to the coil impulses.

The Journal of Steroid Biochemistry and Molecular Biology, 2009

The vitamin D endocrine system is essential for calcium and bone homeostasis. Vitamin D deficits ... more The vitamin D endocrine system is essential for calcium and bone homeostasis. Vitamin D deficits are associated with muscle weakness and osteoporosis, whereas vitamin D supplementation may improve muscle function, body sway and frequency of falls, growth and mineral homeostasis of bones. The loss of muscle strength and mass, as well as deficits in bone formation, lead to poor balance. Poor balance is one of the main causes of falls, and may lead to dangerous injuries. Here we examine balance functions in vitamin D receptor deficient (VDR−/−) mice, an animal model of vitamin D-dependent rickets type II, and in 1␣-hydroxylase deficient (1␣-OHase−/−) mice, an animal model of pseudovitamin D-deficiency rickets. Recently developed methods (tilting box, rotating tube test), swim test, and modified accelerating rotarod protocol were used to examine whether the absence of functional VDR, or the lack of a key vitamin D-activating enzyme, could lead to mouse vestibular dysfunctions. Overall, VDR−/− mice, but not 1␣-OHase−/− mice, showed shorter latency to fall from the rotarod, smaller fall angle in the tilting box test, and aberrant poor swimming. These data suggest that VDR deficiency in mice is associated with decreased balance function, and may be relevant to poorer balance/posture control in humans with low levels of vitamin D.

Proceedings of the National Academy of Sciences, 2002

A primary cause of deafness is damage of receptor cells in the inner ear. Clinically, it has been... more A primary cause of deafness is damage of receptor cells in the inner ear. Clinically, it has been demonstrated that effective functionality can be provided by electrical stimulation of the auditory nerve, thus bypassing damaged receptor cells. However, subsequent to sensory cell loss there is a secondary degeneration of the afferent nerve fibers, resulting in reduced effectiveness of such cochlear prostheses. The effects of neurotrophic factors were tested in a guinea pig cochlear prosthesis model. After chemical deafening to mimic the clinical situation, the neurotrophic factors brain-derived neurotrophic factor and an analogue of ciliary neurotrophic factor were infused directly into the cochlea of the inner ear for 26 days by using an osmotic pump system. An electrode introduced into the cochlea was used to elicit auditory responses just as in patients implanted with cochlear prostheses. Intervention with brain-derived neurotrophic factor and the ciliary neurotrophic factor analo...

Otology & Neurotology, 2008

To assess the biocompatibility of different biopolymers with cochlea implant. Six bioabsorbable p... more To assess the biocompatibility of different biopolymers with cochlea implant. Six bioabsorbable polymers and biostable silicone were used for testing histologic reactions in the cochlea of the rat. The samples were prepared from three 50/50 poly(DL-lactide-co-glycolide) PDLLGA having different inherent viscosity (IV) values and 75/25 poly(DL-lactide-co-epsilon-caprolactone) P(DLLA/CL), poly-epsilon-caprolactone PCL, silicone, and chitosan by extruding the biomaterial as a rod using melt molding (for 50/50 PDLLGAs and 75/25 P(DLLA/CL) and PCL), blending (for silicone), and solving (for chitosan). The rods were cut into samples of diameter of 0.5 mm and length of 2 mm. All the samples were packed and sterilized by gamma irradiation (18 kGy, less than 42 degrees C). Twenty-two male and female Sprague-Dawley rats were used in the study. Four months after the implantation, the animals were killed for histologic observation. Chitosan does not degrade in the cochlea 4 months after implantation and, therefore, stimulates very weak inflammatory reaction. The 50/50 PDLLGA (IV, 0.83 dL/g) degrades in the cochlea 4 months after implantation and does not stimulate inflammatory reaction. The 50/50 PDLLGA (IV, 0.41 dL/g; IV, 0.37 dL/g), 75/25 P(DLLA/CL), PCL, and silicone might induce strong inflammatory reaction in the cochlea. Different degradation property of biomaterials in the cochlea indicates diverse drug releasing time in a controlled way. Chitosan is suitable for long-lasting drug delivery, whereas 50/50 PDLLGA (IV, 0.83 dL/g) favors quicker releasing. Both chitosan and 50/50 PDLLGA (IV, 0.83 dL/g) are ideal materials for cochlear drug delivery.

Otolaryngologic Clinics of North America, 2010

Recent magnetic resonance imaging (MRI) techniques have made it possible to examine the compartme... more Recent magnetic resonance imaging (MRI) techniques have made it possible to examine the compartments of the cochlea using gadolidium-chelate (GdC) as a contrast agent. As GdC loads into the perilymph space without entering the endolymph in healthy inner ears, the technique provides possibilities to visualize the different cochlear compartments and evaluate the integrity of the inner ear barriers. This critical review presents the recent advancements in the inner ear MRI technology, contrast agent application and the correlated ototoxicity study, and the uptake dynamics of GdC in the inner ear. GdC causes inflammation of the mucosa of the middle ear, but there are no reports or evidence of toxicity-related changes in vivo either in animals or in humans. Intravenously administered GdC reached the guinea pig cochlea about 10 minutes after administration and loaded the scala tympani and scala vestibuli with the peak at 60 minutes. However, the perilymphatic loading peak was 80 to 100 minutes in mice after intravenous administration of GdC. In healthy animals the scala media did not load GdC. In mice in which GdC was administered topically onto the round window, loading of the cochlea peaked at 4 hours, at which time it reached the apex. The initial portions of the organ to be filled were the basal turn of the cochlea and vestibule. In animal models with endolymphatic hydrops (EH), bulging of the Reissner's membrane was observed as deficit of GdC in the scala vestibuli. Histologically the degree of bulging correlated with the MR images. In animals with immune reaction-induced EH, MRI showed that EH could be limited to restricted regions of the inner ear, and in the same inner ear both EH and leakage of GdC into the scala media were visualized. More than 100 inner ear MRI scans have been performed to date in humans. Loading of GdC followed the pattern seen in animals, but the time frame was different. In intravenous delivery of double-dose GdC, the inner ear compartments were visualized after 4 hours. The uptake pattern of GdC in the perilymph of humans between 2 hours and 7 hours after local delivery needs to be clarified. In almost all patients with probable or suspected Ménière's disease, EH was verified. Specific algorithms with a 12-pole coil using fluid attenuation inversion recovery sequences are recommended for initial imaging in humans.

Noise and Health, 2011

This study intended to evaluate classical musicians&a... more This study intended to evaluate classical musicians' risk of hearing loss. We studied 63 musicians from four Helsinki classical orchestras. We measured their hearing loss with an audiometer, found their prior amount of exposure to sound and some individual susceptibility factors with a questionnaire, measured their present sound exposure with dosimeters, and tested their blood pressure and cholesterol levels, then compared their hearing loss to ISO 1999-1990's predictions. The musicians' hearing loss distribution corresponded to that of the general population, but highly exposed musicians had greater hearing loss at frequencies over 3 kHz than less-exposed ones. Their individual susceptibility factors were low. Music deteriorates hearing, but by less than what ISO 1999-1990 predicted. The low number of individual susceptibility factors explained the difference, but only reduced hearing loss and not the prevalence of tinnitus.

Nanomedicine, 2014

Aim: To validate a novel sustained delivery system of liposome nanocarriers for inner-ear therapy... more Aim: To validate a novel sustained delivery system of liposome nanocarriers for inner-ear therapy and to investigate the transport pathway for their delivery. Materials & methods: Liposome nanocarriers containing gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (LPS+Gd-DOTA) were developed for MRI tracking the in vitro release profile and for in vivo uptake studies. Results: Encapsulating Gd-DOTA did not modify the liposomes. The LPS+Gd-DOTA nanocarriers were slowly released from a miniature osmotic pump. The LPS+Gd-DOTA moved along the ossicular chain toward the oval window after an epitympanic injection, whereas they traveled directly to the round window after a mesotympanic injection. However, the round window membrane was the major pathway for the LPS+Gd-DOTA to enter the inner ear. LPS+Gd-DOTA were visualized on both sides of the cochlea within 6 days of in vivo delivery via the osmotic pump. Discussion: The novel sustained inner-ear delivery system induced liposome nanocar...

Journal of Neuroscience Research, 2009

The inward-rectifier K 1 channel Kir4.1 is responsible for maintaining cochlear homeostasis and r... more The inward-rectifier K 1 channel Kir4.1 is responsible for maintaining cochlear homeostasis and restoring neural excitability. The large-conductance calcium-activated K 1 channel (BK Ca) plays a key role in phase locking signals in the mammalian inner ear. To evaluate the influence of mitochondrial dysfunction on the expression and subcellular localization of these channels, 3-nitropropionic acid (3-NP) was administered to rat round window membranes for 30 min. Auditory brainstem response was measured both before and 2 hr after 3-NP administration. Immunofluorescent confocal microscopy was used to measure the expression and subcellular localization of Kir4.1 and BK Ca. Alexa Fluor 568-labeled bovine serum albumin (BSA) was applied to round window membranes as a tracer to explore the cochlear distribution of drug delivery and was detected in the lateral wall, spiral ganglion, cochlear nerve, and organ of Corti. Hearing loss of 23 (64.4 SE) and 58 (66.7 SE) dB developed in rats treated with 0.3 and 0.5 mol/liter of 3-NP, respectively. BK Ca was visualized in the cellular membrane and cytoplasm in the upper and middle region of inner hair cells, and it was not affected by 3-NP. Kir4.1 was detected in intermediate cells of the stria, Deiter's cells, and spiral ganglion satellite cells. Kir4.1 failed to reach the perineural cytoplasm of the satellite cells after 3-NP treatment. The results of this study suggest that mitochondrial dysfunction disrupts trafficking of Kir4.1 in spiral ganglion satellite cells. V

International Archives of Occupational and Environmental Health, 2008

Officially 10-26 cases of vibration-induced white fingers (VWF) have been reported annually in Fi... more Officially 10-26 cases of vibration-induced white fingers (VWF) have been reported annually in Finland. It has been suggested that the numbers are underestimated. The purpose of the present study was to estimate the cumulative exposure to hand-arm vibration (HAV) and the prevalence of clinically diagnosed cases of VWF and carpal tunnel syndrome (CTS) in a population of Finnish metal workers and to determine the symptoms and clinical tests that would best predict the diagnosis. A questionnaire on vibration exposure at the workplace and symptoms of the upper extremities was sent to a sample (n = 530) of members of the local Metalworkers Union. Those who reported finger blanching, numbness or tingling of the fingers or symptoms of CTS were invited to take part in clinical examinations. Their cumulative lifelong exposure to HAV was evaluated. Those whose symptoms referred to VWF or CTS were given a cold provocation test with the measurement of finger systolic blood pressure and electroneuromyography of the upper arms. Altogether 285 metal workers (54%) responded to the questionnaire, and 24 new cases of VWF (8.4%) and 12 cases of CTS (4.2%) were diagnosed. In the group of VWF patients, seven workers had both VWF and CTS. All of the workers diagnosed as having VWF also had numbness or tingling in their fingers. Consequently, questions concerning numbness and tingling, a two-point discrimination test, Phalen's test, and Tinell's test had a high predicting value for VWF. The exposure time of the VWF cases did not differ significantly from that of the study group as whole, but the cumulative exposure index was significantly higher. The results suggest that VWF is underdiagnosed in Finland. In screening for the health effects of HAV, sensorineural symptoms of hands should be carefully inquired about and examined in patients complaining of white fingers. More education on the recognition and evaluation of HAV exposure and its health effects is needed.

International Archives of Occupational and Environmental Health, 2006

Hand-arm vibration syndrome (HAVS) consists of vascular and neurological component. Musculoskelet... more Hand-arm vibration syndrome (HAVS) consists of vascular and neurological component. Musculoskeletal component has not been delineated yet. In the present follow-up study, we evaluated the prevalence of HAVS and the cumulative exposure to vibration among a cohort of forestry workers. Special interest was given to numbness and musculoskeletal disorders of upper extremity and neck in forestry workers. A follow-up study starting from 1976 was conducted among forestry workers in Suomussalmi in Finland. Total exposure of hand-arm vibration was recorded during 11 cross-sectional surveys. The last study was carried out in 1995. The lifetime dose of vibration energy was calculated. A cohort of 52 forest workers participated to all 11 cross-sectional surveys 1976-1995. HAVS and musculoskeletal disorders were evaluated. The prevalence of active vibration white finger (VWF) decreased from 13 to 4% in the cross-sectional study. In the cohort VWF decreased from 17 to 8% and numbness increased from 23 to 40%. Rotator cuff syndrome (P=0.034) and epicondylitis (P=0.004) associated with numbness. Regional neck pain was diagnosed in 38% of workers and associated with low back pain. In modeling VWF, the lifelong vibration energy (OR 1.03, CI 1.01-1.05), and smoking (OR 7.36, CI 1.07-50.76) were significant. Numbness was modeled by pain in upper extremities (OR 12.43, CI 2.42-63.80) and neck pain (5.97, CI 1.25-28.39), not by lifelong vibration energy. Right rotator cuff syndrome was modeled by age (OR 2.58, CI 1.04-6.41) and lifelong vibration energy (OR 1.04, CI 1.00-1.07). The prevalence of VWF constantly decreased. Numbness did not follow the vibration exposure profile. Numbness also associated with upper extremity musculoskeletal disorders. Hand-arm vibration associated with the right rotator cuff syndrome in forestry workers.

European Archives of Oto-Rhino-Laryngology, 2013

To elucidate the communication between the middle and inner ear, and the fluid dynamics of the in... more To elucidate the communication between the middle and inner ear, and the fluid dynamics of the inner ear with the perilymphatic fistula (PLF) of the round window membrane (RWM). The PLF of the RWM was created in nine guinea pigs. Gadolinium diethylenetriamine pentaacetic acid bismethylamide (Gd-DTPA-BMA) was delivered into the middle ear and followed in the inner ear using a 4.7 Tesla MRI. Pressure was delivered to the external ear canal of PLF ear in an attempt to enhance the inner ear uptake of Gd-DTPA-BMA. The immediate loading of Gd-DTPA-BMA in the scala tympani of the basal turn was ablated by the outflow of perilymph through the leaking RWM while the oval window passage for Gd-DTPA-BMA was enhanced. There was more Gd-DTPA-BMA distribution in the scala tympani than in the scala vestibuli in the second turn of the PLF cochlea (within 20 min). Signal in the vestibulum and scala vestibuli of the basal turn and rest part of PLF cochlea was greater than that of the control cochlea with intact RWM within 30 min. Pressure applied to the external ear canal tended to enhance the loading of Gd-DTPA-BMA in the perilymphatic scalae of the PLF cochlea. The enhanced oval window passage of Gd-DTPA-BMA was proven by the distorted distribution in the inner ear with PLF. The radial communication of cochlear perilymph was supported by the Gd-DTPA-BMA gradient among the perilymphatic scalae. Applying positive pressure to the external ear canal caused backflow of perilymph into the cochlea which has a potential of transmitting microbes from the middle ear into the inner ear.