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Biomedical subjects

Jukka Ylikoski

Publications and source records attributed to Jukka Ylikoski.

At least 19 recordsLinked to original sources

Radiofrequency induced thermotherapy: an alternative palliative treatment modality in head and neck cancer.

Bipolar radiofrequency induced thermotherapy (RFITT) is a minimally invasive electrosurgical technique characterized by a precise controllable effect in the tissue. It has demonstrable efficacy, safety and reproducibility in the management of solid malignancies. Our aim was to assess the morbidity and efficacy of RFITT as a palliative treatment of head and neck cancer. Prospective, non-randomized case series and analysis. After evaluation by the multidisciplinary Head and Neck Tumour Board at Helsinki University Central Hospital, Finland, 12 consecutive patients with a head and neck cancer without curative treatment possibilities were enrolled into the study. Five patients had pharyngeal carcinomas, one had an unknown primary tumour growing through the skin on the neck, two had a recurrent malignant melanoma originating from the maxillary sinuses, one had a carcinoma of the tongue, two had laryngeal carcinomas, and one had a recurrent adenoid cystic carcinoma of the parotid gland. RFITT was performed with a CelonLabPrecision generator using appropriate electrodes. The treatment was administered under local or general anaesthesia. The subjective morbidity of the treatment was evaluated. The response to the treatment was assessed clinically and with radiological imaging when feasible. All but two of the patients received palliation to their disease. RFITT induced clinically a partial response in ten patients, and there were radiological detectable changes. There were no treatment related complications, and the patients tolerated the treatment well. RFITT in head and neck cancer patients is easy to perform, well tolerated, and induces reduction in the tumour mass. Continuous evaluation of RFITT treatment modality is warranted in selected palliative care patients.

Aged↗

High incidence of Alloiococcus otitidis in children with otitis media, despite treatment with antibiotics.

Acute otitis media (AOM) and otitis media with effusion (OME) are common diseases in childhood. Alloiococcus otitidis is a newly recognized species of gram-positive bacterium which was recently discovered as a pathogen associated with OME. Although some studies show that A. otitidis is frequently detected in children with OME, no study is available concerning the clinical efficiency of antibiotics against this organism. The prevalence of A. otitidis in 116 middle ear effusion specimens from 36 AOM and 52 OME patients was examined by culture and PCR. In addition, the prevalence of the bacterium was retrospectively investigated in relation to antibiotic use. A. otitidis was detected in 20 (50%) AOM and 47 (61%) OME specimens. The organism was the most frequent bacterium in AOM as well as in OME and was highly detected even in patients who had been treated with antibiotics, such as beta-lactams or erythromycin. The incidence of A. otitidis in our study was higher than that in Western countries, and our results suggest that drug-resistant strains of A. otitidis may be frequently spread in Japanese children. Our study suggests that antibiotics such as beta-lactams or erythromycin may not be sufficiently effective to eliminate this organism. Further investigation is expected to reveal the clinical role of the organism in otitis media.

Acute Disease↗

The retinoblastoma gene pathway regulates the postmitotic state of hair cells of the mouse inner ear.

Precursors of cochlear and vestibular hair cells of the inner ear exit the cell cycle at midgestation. Hair cells are mitotically quiescent during late-embryonic differentiation stages and postnatally. We show here that the retinoblastoma gene Rb and the encoded protein pRb are expressed in differentiating and mature hair cells. In addition to Rb, the cyclin dependent kinase inhibitor (CKI) p21 is expressed in developing hair cells, suggesting that p21 is an upstream effector of pRb activity. p21 apparently cooperates with other CKIs, as p21-null mice exhibited an unaltered inner ear phenotype. By contrast, Rb inactivation led to aberrant hair cell proliferation, as analysed at birth in a loss-of-function/transgenic mouse model. Supernumerary hair cells expressed various cell type-specific differentiation markers, including components of stereocilia. The extent of alterations in stereociliary bundle morphology ranged from near-normal to severe disorganization. Apoptosis contributed to the mutant phenotype, but did not compensate for the production of supernumerary hair cells, resulting in hyperplastic sensory epithelia. The Rb-null-mediated proliferation led to a distinct pathological phenotype, including multinucleated and enlarged hair cells, and infiltration of hair cells into the mesenchyme. Our findings demonstrate that the pRb pathway is required for hair cell quiescence and that manipulation of the cell cycle machinery disrupts the coordinated development within the inner ear sensory epithelia.

Animals↗

Induction of CD69 expression and Th1 cytokines release from human peripheral blood lymphocytes after in vitro stimulation with Alloiococcus otitidis and three middle ear pathogens.

Alloiococcus otitidis is a recently discovered pathogen of otitis media. However, only a limited number of studies are available about the pathogenic and immunological role of A. otitidis. The aim of this study was to investigate the activation and the cytokine production of human peripheral blood lymphocytes at the early immune response after stimulation with A. otitidis. After stimulation of whole human peripheral blood lymphocytes for 18 h with whole killed A. otitidis or the three major middle ear pathogens (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis), the expression of CD69 and the production of cytokines were analyzed. The expression of CD69 on T cells and B cells was dose-dependently enhanced after stimulation with A. otitidis. The release of interleukin (IL)-12 was induced after stimulation with A. otitidis, whereas the release of IL-4 was not induced after stimulation with A. otitidis. In addition, the release of interferon (IFN)-gamma was induced after stimulation with A. otitidis. Although the release of IFN-gamma started within 18 h after stimulation with A. otitidis, intracellular production of IFN-gamma was not observed in either CD4+ T cells or CD8+ T cells within 18 h upon stimulation. The patterns of CD69 expression and T helper-type 1 (Th1)-promoting cytokines production were similarly shown when human peripheral blood lymphocytes were stimulated with the other three major pathogens. Our results suggest that A. otitidis has sufficient immunogenic potential to modulate a host immune response, like the other three major middle ear pathogens, and also suggest that the immunogenicity of A. otitidis is very similar, at the early immune response, to that of the three major middle ear pathogens.

Adult↗

Difference in cytokine production and cell activation between adenoidal lymphocytes and peripheral blood lymphocytes of children with otitis media.

We evaluated the immunological potential of adenoidal lymphocytes from children with recurrent otitis media. Interleukin-4 release and CD69 expression were lower in adenoidal lymphocytes than in peripheral blood lymphocytes (PBL). Our results suggest that there may be a difference between the immunological potential of adenoidal lymphocytes and that of PBL in children with otitis.

Adenoids↗

Fgf9 signaling regulates inner ear morphogenesis through epithelial-mesenchymal interactions.

The mammalian inner ear comprises the cochleovestibular labyrinth, derived from the ectodermal otic placode, and the encasing bony labyrinth of the temporal bone. Epithelial-mesenchymal interactions are thought to control inner ear development, but the modes and the molecules involved are largely unresolved. We show here that, during the precartilage and cartilage stages, Fgf9 is expressed in specific nonsensory domains of the otic epithelium and its receptors, Fgfr1(IIIc) and Fgfr2(IIIc), widely in the surrounding mesenchyme. To address the role of Fgf9 signaling, we analyzed the inner ears of mice homozygous for Fgf9 null alleles. Fgf9 inactivation leads to a hypoplastic vestibular component of the otic capsule and to the absence of the epithelial semicircular ducts. Reduced proliferation of the prechondrogenic mesenchyme was found to underlie capsular hypoplasticity. Semicircular duct development is blocked at the initial stages, since fusion plates do not form. Our results show that the mesenchyme directs fusion plate formation and they give direct evidence for the existence of reciprocal epithelial-mesenchymal interactions in the developing inner ear. In addition to the vestibule, in the cochlea, Fgf9 mutation caused defects in the interactions between the Reissner's membrane and the mesenchymal cells, leading to a malformed scala vestibuli. Together, these data show that Fgf9 signaling is required for inner ear morphogenesis.

Animals↗

Alloiococcus otitidis in acute otitis media.

OBJECTIVE: The bacterium Alloiococcus otitidis has been found to be associated with otitis media with effusion (OME). When the culture method is used, its detection rate is low, whereas applying the polymerase chain reaction (PCR) yields significantly higher frequencies. This study was carried out to investigate the incidence of A. otitidis in children with acute otitis media (AOM). METHODS: Multiplex PCR was used to detect A. otitidis together with Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae in the middle ear effusions (MEEs) of 118 children with AOM. The clinical outcome of AOM and the bacterial findings of MEEs were compared. RESULTS: A. otitidis was detected in 25% (30 of 118) of the tested MEE samples. Children over 2 years of age had significantly more often A. otitidis-positive MEEs (37%; 22 of 59) than younger children (14%; 8 of 59) (chi-square test, P<0.01). There were no significant differences in the duration, clinical failures (after antibiotic treatment), or number of recurrences of AOM between the A. otitidis-positive and A. otitidis-negative children. CONCLUSIONS: A. otitidis is found from the MEEs of AOM. The present data suggest that it has no clinical significance in AOM, and it does not increase the risk of developing OME after AOM.

Acute Disease↗

Otologic consequences of blast exposure: a Finnish case study of a shopping mall bomb explosion.

OBJECTIVE: On 11 October, 2002, in the Myyrmanni shopping mall, Vantaa city, Finland, an explosion by a suicide bomber killed 7 people and injured at least 160,44 of whom had ear trauma. We investigated the acute and subacute otologic consequences of the explosion. MATERIAL AND METHODS: Otologic examination of the 29 patients treated for ear trauma at the ENT clinic of the University Hospital of Helsinki was performed during the first month after the explosion, and a questionnaire was completed regarding subjective aural symptoms. Symptoms occurring directly after the explosion and for up to 1 month afterwards were assessed. RESULTS: Of the 29 patients, 66% had tinnitus as the initial symptom, 55% hearing loss, 41% pain in the ears and 28% sound distortion. Tinnitus and hearing loss in combination were experienced by 12 patients (41%). Eight patients who had been situated<10 m from the center of the explosion had a rupture of the tympanic membrane. This supported the initial evaluation by the authorities that the bomb had consisted of approximately 3 kg ammonium nitrate, equivalent to approximately 0.5 kg of trinitrotoluene. It was estimated that some kind of ear injury was likely for individuals situated<70 m from the center of the explosion. CONCLUSIONS: People often think that tinnitus and hearing impairment are naturally occurring phenomena after blast exposure, and if their symptoms resolve they do not seek medical advice. However, some of them may have substantial hearing impairment, particularly at high frequencies. Otologic consultation, or at least an audiometric screening test to exclude hearing impairment, should be performed regardless of symptoms, on the basis of exposure data only. Some symptoms, such as tinnitus and hearing loss, may be permanent consequences of a blast injury and their effect on quality of life may be substantial.

Adolescent↗

Characteristics of acute acoustical trauma in the Finnish Defence Forces.

In spite of strict safety regulations concerning firearm shooting, several hundred conscripts still suffer acute acoustical trauma (AAT) in the Finnish Defence Forces (FDF) every year, resulting in symptoms such as tinnitus and/or hearing impairment. The causes leading to AAT, causative weapons and mode and level of hearing protection were analysed to find out why so many AATs still occur in the FDF. The material consisted of 119 patients of the total 163 AAT patients treated at the Central Military Hospital during the year 2000. In 87.5% of cases, the AATs occurred in unprotected ears. The most common causative weapon was the assault rifle. Most of the AATs occurred during combat training in the field. Immediately after the AAT. 46.7% of conscripts had hearing impairment and 94.2% tinnitus. Hearing loss, tinnitus or both were experienced by 45% of conscripts at the last follow-up. Careful planning of training exercises could probably prevent some but not all AATs.

Adult↗

Magnetic resonance imaging findings in the auditory pathway of patients with sudden deafness.

OBJECTIVES: The objectives of this study were to evaluate magnetic resonance imaging (MRI) findings of patients with sudden sensorineural hearing loss (SSNHL) and to grade the findings based on their clinical importance. STUDY DESIGN: A prospective clinical study. SETTING: A tertiary referral center (university hospital). PATIENTS: MRI findings of 82 consecutive patients with SSNHL fulfilling the inclusion criteria. MAIN OUTCOME MEASURES: We studied 1.0-T MR images that were analyzed by one experienced neuroradiologist. RESULTS: Of the six cases (7%) in which clearly hearing loss was obviously associated with the observed pathology, four patients had an acoustic neuroma in the internal auditory canal or cerebellopontine angle, one patient had changes at the level of pons, and one patient had an obliterated internal carotid artery. Of the six other patients (7%) in which MRI revealed changes that suggest a possible etiology to hearing loss, two patients showed a demyelinating process and four patients showed blood vessel abnormalities such as caroticocavernous fistula, abnormally locating vertebral or basilar artery, and a venous angioma. CONCLUSIONS: Enhanced MR imaging seems to be a useful examination in patients with SSNHL. The aim should not be only to exclude specific retrocochlear etiologies, but by appropriate techniques, MRI could reveal both peripheral and central abnormalities.

Adult↗

Microbiology of chronic hyperplastic sinusitis.

BACKGROUND: Patients with chronic hyperplastic sinusitis (CHS) form a heterogeneous group with similar symptoms and similar treatment despite of possible different mechanisms behind the disease. In the present study we focused on the microbiological findings in CHS and compared these results to the patient history in order to find out a possible explanation for the aetiology and chronicity of CHS. METHODS: In 30 patients the sinus mucus was collected under endoscopic sinus surgery. Samples from 20 healthy volunteers were collected by nasal lavage. Eosinophil staining, bacterial culturing and fungal staining and culturing were done. Histological samples were obtained from all patients. RESULTS: Bacterial cultures were positive in 93% of the patients compared to 70% in controls. Staphylococcus aureus and coagulase-negative Staphylococci were the two most common findings in both groups. A total of seven patients had positive fungal finding. The only fungal genus found was Aspergillus. In the control group no samples were positive for fungi. CONCLUSIONS: Microbiological findings do not seem to explain the chronic course of CHS, but fungi may play some part in the pathophysiology of the disease. These results may be more a reflection of a change in the environment in the paranasal sinuses and a change in normal flora than the actual cause of CHS.

Adult↗

The ototoxic interaction of styrene and noise.

The interaction between noise and inhaled styrene on the structure and function of the auditory organ of the male Wistar rat was studied. The animals were exposed either to 600 ppm, 300 ppm or 100 ppm styrene (12 h/day, 5 days/week, for 4 weeks) alone or in combination with a simultaneous 100-105 dB industrial noise stimulant. Auditory sensitivity was tested by auditory brainstem audiometry at 1.0, 2.0, 4.0 and 8.0 kHz frequencies. Inner ear changes were studied by light microscopy. Exposure to 600 ppm styrene alone caused a 3 dB hearing loss only at the highest test frequency (8 kHz). Quantitative morphological analysis of cochlear hair cells (cytocochleograms) showed a severe outer hair cell (OHC) loss particularly in the third OHC row of the upper basal and lower middle coil. Exposure to noise alone caused only a mild hearing loss (2-9 dB), and only an occasional loss of OHCs (<1% missing). Exposure to the combination of noise and 600 ppm styrene caused a moderate flat hearing loss of 23-27 dB. The cytocochleograms showed a more severe damage of the OHCs than after exposure to 600 ppm styrene alone. The inner hair cells were found to be destroyed in some animals in the upper basal turn only after the combination exposure. Only in combination with noise exposure, the lower styrene concentrations (100 and 300 ppm) induced a hearing loss which was equivalent to that seen after exposure to noise alone. We conclude that: (1) There is an ototoxic interaction between styrene and noise. (2) Synergism is manifested only if styrene is applied in concentrations above the critical level (between 300 and 600 ppm in this study).

Animals↗

The clinical role of Alloiococcus otitidis in otitis media with effusion.

OBJECTIVE: To investigate the presence of Alloiococcus otitidis (A. otitidis) in MEEs from patients with otitis media with effusion (OME) using PCR and to correlate the findings with the clinical picture of children with OME for assessing the clinical role of A. otitidis in OME. METHODS: Bacterial culture and PCR were used to detect A. otitidis, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in MEE samples from 123 patients with OME. The culture and PCR results and the clinical picture of the patients were compared. RESULTS: Bacteria were cultured in 55 (45%) of the 123 MEEs, and major pathogens (S. pneumoniae, H. influenzae and M. catarrhalis) were found in 40 (33%); A. otitidis was not found in culture. PCR of the MEEs yielded positive results for one or more of the four tested pathogens in 108 (88%) of the samples and 25 (20%) were positive for A. otitidis. The effusions that persisted 3 months or longer had a higher prevalence of A. otitidis than those with shorter durations (P=0.03). A. otitidis was found to be more often positive in PCR in mucoid MEEs than in mucoserous MEEs (30 vs. 9%; P=0.015). CONCLUSIONS: While A. otitidis is extremely difficult to detect with bacterial culture, PCR provides a sensitive and specific means for detecting it. A. otitidis is associated with a more prolonged course and mucoid MEEs in OME. Thus, its existence seems to be related to a more chronic stage of OME, but its pathogenic potential should be the subject of further investigation.

Bacterial Typing Techniques↗

FGFR1 is required for the development of the auditory sensory epithelium.

The mammalian auditory sensory epithelium, the organ of Corti, comprises the hair cells and supporting cells that are pivotal for hearing function. The origin and development of their precursors are poorly understood. Here we show that loss-of-function mutations in mouse fibroblast growth factor receptor 1 (Fgfr1) cause a dose-dependent disruption of the organ of Corti. Full inactivation of Fgfr1 in the inner ear epithelium by Foxg1-Cre-mediated deletion leads to an 85% reduction in the number of auditory hair cells. The primary cause appears to be reduced precursor cell proliferation in the early cochlear duct. Thus, during development, FGFR1 is required for the generation of the precursor pool, which gives rise to the auditory sensory epithelium. Our data also suggest that FGFR1 might have a distinct later role in intercellular signaling within the differentiating auditory sensory epithelium.

Animals↗

Functional and morphological effects of styrene on the auditory system of the rat.

The effect of inhaled styrene on the structure and function of the auditory organ of the male Wistar rat was studied. The animals were exposed either to 600, 300 or 100 ppm styrene (12 h/day, 5 days/week, for 4 weeks). Auditory sensitivity was tested prior to and after the exposure by auditory brain stem audiometry (ABR) at frequencies of 1.0, 2.0, 4.0 and 8.0 kHz. Inner ear morphological changes were studied by light- and electron-microscopy. Exposure to 600 ppm styrene caused a 3 dB hearing loss only at the highest test frequency (8 kHz). Quantitative morphological analysis of cochlear hair cells (cytocochleograms) showed that 600 ppm styrene caused a severe outer hair cell (OHC) loss particularly in the third OHC row of the upper basal and lower middle coil. The inner hair cells were usually intact. Exposure to lower styrene concentrations (100 and 300 ppm) caused no unequivocal functional deficit or hair cell damage. We conclude that there appears to be a concentration threshold for styrene ototoxicity in rats (between 300 and 600 ppm).

Administration, Inhalation↗

Blockade of c-Jun N-terminal kinase pathway attenuates gentamicin-induced cochlear and vestibular hair cell death.

The ototoxic action of aminoglycoside antibiotics leading to the loss of hair cells of the inner ear is well documented. However, the molecular mechanisms are poorly defined. We have previously shown that in neomycin-exposed organotypic cultures of the cochlea, the c-Jun N-terminal kinase (JNK) pathway--associated with stress, injury and apoptosis--is activated in hair cells and leads to their death. We have also shown that hair cell death can be attenuated by CEP-1347, an inhibitor of JNK signalling [Pirvola et al., J. Neurosci. 20 (2000) 43-50]. In the present study, we demonstrate that gentamicin-induced ototoxicity leads to JNK activation and apoptosis in the inner ear hair cells in vivo. We also show that systemic administration of CEP-1347 attenuates gentamicin-induced decrease of auditory sensitivity and cochlear hair cell damage. In addition, CEP-1347 treatment reduces the extent of hair cell loss in the ampullary cristae after gentamicin intoxication. Particularly, the inner hair cells of the cochlea and type I hair cells of the vestibular organs are protected. We have previously shown that also acoustic overstimulation leads to apoptosis of cochlear hair cells and that CEP-1347 can attenuate noise-induced sensory cell loss. These results suggest that activation of the JNK cascade may be a common molecular outcome of cellular stress in the inner ear sensory epithelia, and that attenuation of the lesion can be provided by inhibiting JNK activation.

Animals↗

Blockade of c-Jun N-terminal kinase pathway attenuates gentamicin-induced cochlear and vestibular hair cell death.

The ototoxic action of aminoglycoside antibiotics leading to the loss of inner ear hair cells is well documented. However, the molecular mechanisms are poorly defined. We have previously shown that in neomycin-exposed cochlear organotypic cultures, the c-Jun N-terminal kinase (JNK) pathway - associated with stress, injury and apoptosis - is activated in hair cells. We have shown that hair cell death can be attenuated by CEP-1347, an inhibitor of JNK signaling (). In the present study, we demonstrate that gentamicin-induced ototoxicity leads to JNK activation and apoptosis in the inner ear hair cells in vivo. We show that systemic administration of CEP-1347 attenuates gentamicin-induced decrease of auditory sensitivity and cochlear hair cell damage. In addition, CEP-1347 treatment reduces the extent of hair cell loss in the ampullary cristae after gentamicin intoxication. Particularly, the inner hair cells of the cochlea and type I hair cells of the vestibular organs are protected. Our previous data have shown that also acoustic overstimulation can cause apoptotic death of cochlear hair cells and that CEP-1347 can attenuate noise-induced hair cell loss. Thus, our results imply that activation of JNK cascade may be a common molecular outcome of cellular stress in the inner ear sensory epithelia and that attenuation of the lesion can be provided by inhibiting JNK activation.

Animals↗