Prevalence of otitis media with effusion among children in Xi'an, China: a randomized survey in China's mainland.

OBJECTIVES: We sought to identify the prevalence of otitis media with effusion (OME) in urban Chinese children in Xi'an, China. METHODS: Five kindergartens and 3 primary schools were randomly selected in the urban area of Xi'an. Screening otoscopic and tympanometric examinations were performed on 2,902 children (1,491 boys and 1,411 girls) 2 to 8 years of age. Children with an abnormal tympanogram and simultaneous otomicroscopic signs of effusion were given a diagnosis of OME. RESULTS: The overall prevalence of OME was 4.3%. By age group, the prevalence was 14.0% in 2-year-olds, 8.3% in 3-year-olds, 5.0% in 4-year-olds, 4.9% in 5-year-olds, 2.8% in 6-year-olds, 1.7% in 7-year-olds, and 3.2% in 8-year-olds. The prevalence rate for OME was 4.7% for boys versus 3.9% for girls, and 3.0% in the right ear versus 2.7% in the left, showing no statistically significant difference between genders or between ear sides (p > 0.05). CONCLUSIONS: The prevalence of OME in urban areas of Xi'an is not high in comparison with that of the same age group in surrounding areas.

Visualization of horizontal canal benign paroxysmal positional vertigo using 3DCT imaging and its assessment.

BACKGROUND: There have been no useful imaging methods to diagnose benign paroxysmal positional vertigo (BPPV), a common cause of vertigo, depending on the characteristic symptom. OBJECTIVE: To visualize horizontal canal (HC) BPPV using 3DCT and assess its clinical usefulness. SUBJECTS AND METHODS: Ten BPPV patients were diagnosed with distinct BPPV, canalolithiasis, and cupulolithiasis of the HC (hc-BPPV, hc-BPPV-cu), which were definitely diagnosed on the basis of criteria of BPPV by the Barany Society and 10 healthy subjects without a history of dizziness were investigated using 3DCT with several different CT window values (CTWVs). RESULTS: The HCs of BPPV patients were clearly visualized and the luminal aspects showed differences among ears with cupulolithiasis, canalolithiasis and no symptoms healthy subjects. CONCLUSIONS AND SIGNIFICANCE: 3DCT images visualized the characteristic changes of the HC of patients with BPPV compared to healthy subjects. The HC images were coincident with the clinical condition of cupulolithiasis and canalolithiasis. This imaging technique is clinically useful for diagnosing, treating and assessing the prognosis of HC BPPV.

Blocking EGFR in the liver improves the tumor-to-liver uptake ratio of radiolabeled EGF.

Overexpression of epidermal growth factor receptor (EGFR) in several types of malignant tumors correlates with disease progression. EGFR could, therefore, be an excellent candidate for targeted radionuclide diagnostics. However, the high natural expression of EGFR in the liver may be problematic. The aim of this study was to improve the tumor-to-liver ratio of radiolabeled epidermal growth factor (EGF) by blocking its uptake by the liver with a nonradiolabeled EGFR-targeting molecule in tumor-bearing mice. Intraperitoneally injected nonradiolabeled EGF was first evaluated as a blocking agent, preadministered at various time intervals before intravenous injection of (125)I-labeled EGF. The anti-EGFR Affibody molecule (Z(EGFR:955))(2) was then assessed as a blocking agent of (111)In-labeled EGF in a dual isotope study (50, 100, and 200 microg, preadministered 30 or 60 min before (111)In-EGF). The 30-min preadministration of nonradiolabeled EGF significantly decreased (125)I-EGF uptake in the liver, whereas uptake in the tumor remained unchanged. Furthermore, preadministration of only 50 microg (Z(EGFR:955))(2) as a blocking agent 30 min before the (111)In-EGF decreased the uptake of (111)In-EGF by the liver and increased its uptake by the tumor, thereby increasing the tumor-to-liver ratio sixfold. We conclude that the Affibody molecule (Z(EGFR:955))(2) shows promise as a blocking agent that could enhance the outcome of radionuclide-based EGFR-expressing tumor diagnostics and imaging.

Localization of melatonin and its receptors (melatonin 1a and 1b receptors) in the mouse inner ear.

Background: In the inner ear, evidence has been gathered indicating that melatonin plays important roles in inner ear physiology and pathophysiology. However, no attempt has been made previously to investigate the localization or expression of melatonin and its receptors in the whole inner ear. Aims/objectives: To analyze the presence of melatonin and its receptors in the normal mouse inner ear. Material and methods: C57BL6/J mice were used in this study. The localizations of melatonin, MT1a and MT1b in the inner ear, i.e. cochlea, vestibular end organs, vestibular ganglion and endolymphatic sac (ES), were studied by immunohistochemistry. Results: The organ of Corti, spiral ganglion, vestibular ganglion, vestibular sensory cells, vestibular dark and transitional cells, and ES epithelial cells showed an immunofluorescence reaction to melatonin, MT1a and MT1b. Conclusion and significance: The present findings show that melatonin and its receptors (MT1a and MT1b) are present in the inner ear, thus supporting the hypothesis that melatonin plays a physiological role in the inner ear.

Targeting CD44v6 expressed in head and neck squamous cell carcinoma: preclinical characterization of an 111In-labeled monoclonal antibody.

In patients with head and neck squamous cell carcinoma (HNSCC) radioimmunodiagnosis could offer a more specific and sensitive tumor diagnostic method. Our aim was to evaluate the labeling and biodistribution of the novel radioimmunoconjugate (111)In-cMAb U36. In this study cMAb U36, targeting CD44v6, and huA33, as a negative control, were labeled with indium-111, using the chelator CHXA''-DTPA. Immunoreactivity assays and binding studies were performed in vitro. Biodistribution and tumor imaging were conducted after intravenous injection of the radioimmunoconjugate to nude mice bearing HNSCC xenografts expressing CD44v6. The immunoreactive fraction was very high and the binding was CD44v6-specific. In vivo results demonstrated a promising biodistribution, with tumors clearly accumulating radioactivity with time. At 168 h postinjection (p.i.) the tumor uptake was 54.7 +/- 16.6% injected dose/g. The cMAb U36 had significantly (p < 0.05) higher uptake in tumors 72 h p.i. compared to huA33. We produced a novel radioimmunoconjugate targeting CD44v6 for possible use in the detection of HNSCC. The conjugate demonstrates no adverse effects from labeling and a favorable biodistribution.

Lip muscle training in stroke patients with dysphagia.

CONCLUSION: Training with an oral screen can improve lip force (LF) and swallowing capacity (SC) in stroke patients with oropharyngeal dysphagia, irrespective of the duration of pretreatment of dysphagia, and irrespective of the presence or absence of central facial paresis. It is more plausible that treatment results are attributable to sensory motor stimulation and the plasticity of the central nervous system than to the training of the lip muscles per se. OBJECTIVES: A close relationship has been demonstrated between LF and SC in stroke patients whether or not they are affected by facial paresis. It is not known how training of lip function can improve swallowing capacity. The present study was therefore designed to ascertain: (i) if training with an oral screen can improve the LF and SC of stroke patients with oropharyngeal dysphagia; to establish (ii) if improvement in LF and SC is connected with the presence or absence of central facial palsy, (iii) on the interval between stroke onset and initiation of treatment, (iv) on age, or (v) on sex. SUBJECTS AND METHODS: This was a retrospective study of 30 stroke patients, 49-88 years old, who were investigated with a Lip Force Meter, LF100 (LF100) and a swallowing capacity test (SCT) before and after a period of self-training lasting at least 5-8 weeks, using an oral screen. Initial central facial paresis was present in 24 patients. RESULTS: The median LF was 7 Newtons (N) (range 0-27) before treatment and 18.5 N (range 7-44) after treatment (p < 0.001). The median SC was 0 ml/s (range 0-9.1) before treatment and 12.1 ml/s (range 0-36.7) at follow-up (p < 0.001). There was no significant difference in swallowing improvement between patients with versus those without facial paresis. The interval between stroke attack and start of treatment, ranging from a few days up to 10 years, had no significant influence on the treatment results, nor did age or sex. The facial paresis was improved or at least ameliorated in all patients after the lip training period.

A new animal model for Ménière's disease.

CONCLUSION: A new murine model for the study of Ménière's disease has been developed by treatment with both lipopolysaccharide (LPS) and aldosterone. Induction of vestibular dysfunction in the hydropic animal model may entail additional stress such as reduced inner ear blood flow, and sudden acute changes in endolymph volume and/or pressure. OBJECTIVE: The purpose of this study was to develop a more suitable animal model, showing closer resemblance to the pathophysiological process in Ménière's disease. MATERIALS AND METHODS: Adult CBA/J mice were treated by intratympanic injection of LPS, intraperitoneal injection of aldosterone, or injection of both LPS and aldosterone. Morphological analyses were performed in the cochlea and endolymphatic sac. RESULTS: All experimental animals showed mild to moderate endolymphatic hydrops. Those treated with both LPS and aldosterone showed reversible vestibular dysfunction after the intratympanic injection of epinephrine.

Effect of acute endolymphatic hydrops overload on the endolymphatic sac.

CONCLUSIONS: Homeostasis of endolymph volume is a complex mechanism, in which the endolymphatic sac (ES) may play an important role. OBJECTIVES: To elucidate the effect of acute endolymphatic hydrops (EH) on the ES and to gain further information about the volume and pressure regulative function of the ES. MATERIALS AND METHODS: Distilled water was injected into the middle ear cavity of adult CBA/J mice. The ESs were studied morphologically by light and transmission electron microscopy. RESULTS: Mild EH was found, particularly in the upper turn of the cochlea. Acute EH led to an increase in the size of the ES lumen, accompanied by collapse of the lateral intercellular spaces and dense perisaccular tissue, changes which had reversed 2 h after the injection.

Effect of inner ear blood flow changes on the endolymphatic sac.

CONCLUSIONS: That the endolymphatic sac (ES) reacts to changes in inner ear blood flow may be important for homeostasis of the inner ear fluid volume and pressure. OBJECTIVES: To elucidate the effect of changes in inner ear blood flow on the ES and to learn more about the volume and pressure regulatory function of the ES. MATERIALS AND METHODS: Epinephrine or sodium nitroprusside (SNP) was injected into the middle ear cavity of adult CBA/J mice. The ES were analyzed morphologically by light microscopy. RESULTS: Epinephrine reduced the luminal size of the ES leading to an accumulation of intraluminal homogeneous substance. Injection of SNP increased the size of the ES lumen, accompanied by a collapse of the lateral intercellular space (LIS) and dense perisaccular tissue. These changes were almost reversed 4 h after injection.

Quantification of CD44v6 and EGFR expression in head and neck squamous cell carcinomas using a single-dose radioimmunoassay.

BACKGROUND: In the growing field of tumor targeting, there is an urgent need to profile suitable molecular targets. In this study, CD44v6 and EGFR expression was quantified in samples of patients with head and neck squamous cell carcinoma (HNSCC) using a single-dose (SD) radioimmunoassay. METHODS: The SD radioimmunoassay using 125I-chimeric monoclonal antibody (cMAb) U36 and 125I-cMAb cetuximab was first validated and then applied to quantify the expression of their target antigen molecules, CD44v6 and EGFR, in patient samples. Results were compared to immunohistochemical staining. RESULTS: The SD assay provided sensitive quantitative values of the molecular targets studied, generally agreeing with the immunohistochemistry (IHC) results. The results indicated that expression of CD44v6 (0.2-20 nmol/mug membrane) was generally higher than that of EGFR (0.6-2.3 nmol/microg membrane) in the tumor samples analyzed, which corresponded to an average of 700,000 and 90,000 antigen molecules per cell, respectively. CONCLUSIONS: The SD radioimmunoassay is simple, reliable, and can be performed on a small amount (50 mg) of tissue. This assay could be a useful tool in the growing field of personalized cancer therapy, and can be used as a complement to IHC. In the tumors studied, CD44v6 was generally expressed at a higher level than EGFR, which might suggest that it could be more readily targeted by MAbs.

Radioimmunotherapy with astatine-211 using chimeric monoclonal antibody U36 in head and neck squamous cell carcinoma.

OBJECTIVES: In advanced head and neck squamous cell carcinoma (HNSCC), there is a need for an adjuvant treatment. We aim to evaluate the biodistribution and therapeutic effect of radioimmunotherapy using the alpha emitting, astatine-211-labeled, chimeric monoclonal antibody U36 (U36) on the HNSCC cell line UT-SCC7 in vivo. STUDY DESIGN: Xenograft tumors were inoculated subcutaneously in nude mice. Astatine-211-labeled U36 was injected intravenously with or without blocking of target with nonlabeled U36. METHODS: In the biodistribution experiments, radioactivity was measured in tumors and various organs at set time points. In the therapeutic experiments, two groups (with or without blocking) received therapy, and the tumor growth was compared with that of controls. In addition, one group received nonlabeled U36 only. RESULTS: The biodistribution experiments demonstrated that astatine-211-labeled U36 could target UT-SCC7 xenografts in nude mice. With time, uptake increased in tumors and decreased in normal organs. Nonlabeled U36 did not influence tumor growth. In the two therapy groups, 18 of 20 tumors responded to therapy by decreasing or stabilizing their volumes. Significant difference was seen between the treated groups and the controls (P < .05). CONCLUSION: The study illustrates the specific binding of astatine-211-labeled U36 to HNSCC and suggests radioimmunotherapy with the alpha emitting radionuclide to be a useful treatment modality.

Clinical impact of positron emission tomography (PET) with (18F)fluorodeoxyglucose (FDG) in head and neck tumours.

CONCLUSION: PET plays an important role in staging, on suspicion of recurrence and for detection of occult primary tumours in the head and neck. OBJECTIVE: Since 1998 we have used positron emission tomography (PET) with (18F)fluorodeoxyglucose (FDG) to assess selected patients. This procedure has often helped in making decisions on staging and treatment. PATIENTS AND METHODS: The case records of the first 80 patients (104 PET examinations) were studied retrospectively. RESULTS: A total of 39 examinations were performed for staging. PET detected all primary tumours except two (stage T1), and staging was adjusted after 13%. In all, 33 PET examinations were performed on suspicion of recurrent tumour. In 52% of these PET determined further treatments; in 21% PET had a direct impact on the surgical planning. In 18 patients with metastases from an occult primary tumour, PET detected 39% of those tumours; in 22% it was the sole modality to do so. No recurrences or second primary tumours were detected when PET was used for follow-up of clinically cured patients. Results were similar when squamous cell carcinomas (SCCs) were considered alone as compared to the complete material. The mean standardized uptake value (SUV) was higher for cases deemed tumour-positive than in negative cases.

Protective effect of edaravone against endolymphatic hydrops.

CONCLUSION: Our findings suggest that edaravone prevented the production of reactive oxygen species (ROS). Edaravone also delayed the formation of endolymphatic hydrops in guinea pigs, but had no effect on endolymphatic hydrops. OBJECTIVE: To analyse the protective effect of a free radical scavenger, edaravone, on endolymphatic hydrops. MATERIALS AND METHODS: Guinea pigs were subjected to surgical obliteration of the endolymphatic duct (ED). For the detection of ROS, group 1 received intraperitoneal injections of edaravone (3 mg/kg/day) for 2 days, group 2 received edaravone for 2 weeks, group 3 saline for 2 days, and group 4 saline for 2 weeks. ROS production by the organ of Corti and stria vascularis was examined by using dihydrotetramethylrosamine. For the morphological analysis, guinea pigs were divided into five groups, i.e. 2 or 4 weeks after ED obliteration, 2 weeks with edaravone, first or last 2 weeks with edaravone and sacrificed 4 weeks after ED obliteration. Increases in the ratios of the cross-sectional area of scala media were analysed quantitatively to assess the degree of endolymphatic hydrops among the above-mentioned five groups of the hydropic cochlea. RESULTS: ROS was detected both in the organ of Corti and in the lateral wall of cochleae 2 days after ED obliteration. Edaravone prevented the production of ROS and also attenuated the formation of endolymphatic hydrops in the acute hydrops group.

Gastric-type H+,K+-ATPase in mouse vestibular end organs.

CONCLUSION: Gastric type H+,K+-ATPase in the vestibular end organs may be of importance for K+ circulation and may also be related to pH regulation in vestibular end organs and endolymphatic sac. OBJECTIVE: To analyze the expression of gastric-type H+,K+-ATPase in normal mouse vestibular end organs. METHODS: 8 weeks old CBA/J mice were used in this study. The presence of gastric-type H+,K+-ATPase α and ß in the vestibular end organs, viz. utricle, saccule, ampulla, vestibular ganglion, and endolymphatic sac, was investigated using immunohistochemistry. RESULTS: In the vestibular end organs, H+,K+-ATPase α and ß were almost identical. H+,K+-ATPase was expressed in sensory cells, the basolateral surface of dark cells, fibrocytes, in vestibular ganglion cells, and in the upper region of the endolymphatic sac epithelial cells.

Protective effect of edaravone against the ototoxicity of Pseudomonas aeruginosa exotoxin A.

CONCLUSION: Our findings suggest that edaravone can protect against cochlear damage caused by Pseudomonas aeruginosa exotoxin A (PaExoA). OBJECTIVE: To analyze the protective effect of a free radical scavenger, edaravone, against the ototoxicity resulting from exposure of the middle ear to PaExoA. MATERIAL AND METHODS: In nine groups of albino rats the following solutions were instilled either via the tympanic membrane into the round window niche [intratympanically (i.t.)] or intravenously (i.v.): edaravone (i.v.); edaravone (i.t.); PaExoA (i.t.) + edaravone (i.t.; simultaneously); PaExoA (i.t.) + edaravone (i.t.; 1 h after); PaExoA (i.t.) + edaravone (i.t.; 24 h after); PaExoA (i.t.) + edaravone (i.v.; simultaneously); PaExoA (i.t.) + edaravone (i.v.; 1 h after); PaExoA (i.t.) + edaravone (i.v.; 24 h after); PaExoA (i.t.) + saline (i.v.). Frequency-specific (2-20 kHz) auditory brainstem responses were measured to determine hearing thresholds before and 2, 5 and 10 days after instillation. RESULTS: PaExoA had penetrated from the middle ear into the cochlea and caused hearing loss. This impairment was blocked by intratympanic injection of edaravone when given simultaneously or 1 h after the first instillation of PaExoA, or by intravenous injection of edaravone when given simultaneously. There were significant differences in protective effect between the intratympanic and intravenous routes.

Ménière's disease: a long-term follow-up study of bilateral hearing levels.

CONCLUSION: It is suggested that a holistic factor - such as psychological stress--is involved in Menière's disease (MD) and that the pathological changes in MD may be a result not only of endolymphatic hydrops but also of disorders affecting the entire cochlea. PATIENTS AND METHODS: Changes in the hearing of 51 patients with unilateral MD were investigated to ascertain the correlation between changes in hearing loss (a) in the affected ear vs the contralateral ear and (b) at low frequencies vs high frequencies. RESULTS: About half of the MD patients showed a significant positive correlation between the hearing level in the affected ear and that in the contralateral ear and also between the average hearing level at lower frequencies and that at 8 kHz. These tendencies were more pronounced in patients with severe fluctuation of hearing and/or severe hearing loss.

Localization of histamine (H1, H2, H3 and H4) receptors in mouse inner ear.

Conclusion The present findings show that all four types of histamine receptors (H1R, H2R, H3R, and H4R) are present in the inner ear, thus supporting the hypothesis that histamine plays a physiological role in the inner ear. Objective To analyse the presence of histamine receptors in the normal mouse inner ear. Methods CBA/J mice were used in this study. The localization of H1R, H2R, H3R, and H4R in the inner ear, i.e. cochlea, vestibular end organs, vestibular ganglion, and endolymphatic sac, was studied by real-time PCR and immunohistochemistry. Results The mRNA for each receptor sub-type was detected in the inner ear. In the immunohistochemical study, the organ of Corti, spiral ganglion, vestibular ganglion, vestibular sensory epithelium, and endolymphatic sac cells showed an immunofluorescent reaction to all histamine receptors.

Localization of sirtuins (SIRT1-7) in the aged mouse inner ear.

CONCLUSION: The expression of sirtuin in vestibular end organs and cochlea responds differently to age-related changes. Down-regulation of SIRT1, 3, and 5 in the cochlea may weaken the protective activity regarding degeneration of the organ of Corti as well as of spiral ganglion cells, resulting in the development of age-related hearing loss. An increase in SIRT 1, 4, or 5 in vestibular tissue could indicate an increased need of detoxification of reactive oxygen species and an increased anti-ageing potential. OBJECTIVE: To analyse the expression of sirtuins (SIRT1-7) in the normal young and old mouse inner ears. METHODS: Young (8 weeks) and old (22 months) CBA/J mice were used in this study. Localization of SIRT1-7 in the inner ear, i.e. cochlea, vestibular end organs, and vestibular ganglion, was investigated using real-time PCR and immunohistochemistry. RESULTS: In the vestibular end organs, the expression of SIRT1, 2, 4, 5 (both mRNA and protein), SIRT6, and 7 (only mRNA) was found to be increased, while a slightly decreased immunoreactivity was observed in SIRT3. In the cochlea, the expression of SIRT1, 3, and 5 (both mRNA and protein) was decreased in the old mice, whereas no noticeable difference was observed regarding SIRT2, 4, 6, or 7.

Nitro-L-arginine methyl ester: a potential protector against gentamicin ototoxicity.

The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.

Radical scavengers: a remedy for presbyacusis. A pilot study.

CONCLUSION: The results of this study suggest that treatment with radical scavengers has the potential to become an effective new therapy for presbyacusis. OBJECTIVE: To assess the efficacy of treatment with the radical scavengers rebamipide and vitamin C for presbyacusis. MATERIAL AND METHODS: Rebamipide (300 mg/day) and vitamin C (600 mg/day) were taken orally for at least 8 weeks by 23 patients with presbyacusis. RESULTS: Hearing levels after treatment were significantly improved at 125, 250, 500 and 8000 Hz but unchanged at 1000, 2000 and 4000 Hz.