Publications by authors named "Kumiko Hosokawa"

25 Publications

  • Page 1 of 1

Postoperative Course of Pars Flaccida Cholesteatoma Patients With Habitual Sniffing.

Otol Neurotol 2020 12;41(10):e1214-e1218

Department of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine.

Objective: To investigate the effects of habitual sniffing on the postoperative course of pars flaccida cholesteatoma.

Study Design: Retrospective case series study.

Setting: University hospital.

Patients: Forty-nine patients (53 ears) with pars flaccida cholesteatoma and history of habitual sniffing before the initial operation.

Interventions: Patients were divided into a "sniffing cessation group" characterized by sniffing cessation and a "continual sniffing group" characterized by continuation of sniffing despite instructions for conscious cessation.

Main Outcome Measures: Hearing level, tympanic membrane findings, tympanograms, mastoid cell development before the operation, and pneumatization 1 year postoperatively.

Results: The sniffing cessation and continual sniffing groups comprised 35 patients (38 ears) and 14 patients (15 ears), respectively. The average postoperative hearing was slightly better in the continual sniffing group. In the sniffing cessation group, retractions were evident in significantly fewer cases. Retractions were observed in all continual sniffing group cases, with a high percentage of severe retractions, wherein the bottom was not visible. Type A tympanogram was predominant in the sniffing cessation group. Mastoid cell development was not significantly different between the two groups. Satisfactory pneumatization was significantly more common in the sniffing cessation group (Fisher's exact test, p < 0.005).

Conclusion: Conscious cessation of the sniffing habit could reduce the risk of postoperative retraction and improve pneumatization in patients with pars flaccida cholesteatoma. The presence or absence of the sniffing habit after surgery is a defining factor in postoperative prognosis (retraction, recurrence), and may be a determinant for decisions regarding surgical approach.
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http://dx.doi.org/10.1097/MAO.0000000000002811DOI Listing
December 2020

Immunohistochemical location of Na, K-ATPase α1 subunit in the human inner ear.

Hear Res 2021 Feb 13;400:108113. Epub 2020 Nov 13.

Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, USA. Electronic address:

Na, K-ATPase (Na,K-ATPase) is an ubiquitous enzyme in the inner ear and a key factor in the maintenance of the osmotic gradient of the endolymph. This study uses Na,K-ATPase α1 subunit immunoreactivity (IR) to identify cellular structures in the normal and disease human cochlea. Formalin-fixed celloidin-embedded (FFCE) human temporal bone sections were immunoreacted with mouse monoclonal antibodies against Na,K-ATPase α1 subunit. Na,K-ATPase α1 IR was examined in the cochlea of 30 patients: four with normal hearing, 5 with Meniere's disease, and 21 with other inner ear diseases: 11 male, 19 female; ages 42 to 96 years-old (yo), average age of 77 yo. Na,K-ATPase α1 IR area was quantified using the ImageJ software program. Na,K-ATPase α1 IR was located in the stria vascularis, and in type I, II and IV fibrocytes of the spiral ligament in the cochlea from patients with normal hearing. Na,K-ATPase α1 IR was seen in Deiters's cells and inner phalangeal cells of the organ of Corti. Na,K-ATPase α1 IR was present in satellite cells that surround the neurons of the spiral ganglia. In the inner ear of pathological specimens, Na,K-ATPase IR area was decreased (compared to the normal) in the stria vascularis, supporting cells in the organ of Corti and satellite cells of the spiral ganglia. These results show that Na,K-ATPase α1 IR is a good marker to identify cellular structures of the human inner ear and may be used to study cellular changes in the cochlea associated with aging and disease. The ubiquitous localization of Na,K-ATPase α1 in the human cochlea is consistent with the Na,K-ATPase role in ionic homeostasis and osmolarity, similar to that seen in animal models.
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http://dx.doi.org/10.1016/j.heares.2020.108113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796994PMC
February 2021

Rubbing the skin when removing makeup cosmetics is a major factor that worsens skin conditions in atopic dermatitis patients.

J Cosmet Dermatol 2021 Jun 26;20(6):1915-1922. Epub 2020 Oct 26.

Skin Care Products Research, Kao Corporation, Tokyo, Japan.

Background: Many patients with atopic dermatitis (AD) know that harsh rubbing of their skin might worsen their skin symptoms. They consider that the force they use to rub their skin when removing their makeup cosmetics should not be hard and their cleansing habits could worsen their skin symptoms. However, we presume that the force they use to rub their skin may still be strong and might worsen their skin symptoms.

Aims: We characterized the effects of rubbing the skin of AD patients during cleansing of makeup cosmetics.

Patients/methods: A cleansing oil which has a higher cleansing ability compared the cleansers used daily by the subjects but required less rubbing force was used. We performed a 4-week clinical trial of this cleansing oil on 35 female subjects who had mild AD skin symptoms on their faces. Each subject used the cleansing oil instead of their usual makeup remover without changing their other facial skin care habits. Prior to the study, and at the end of weeks 1 and 4, the skin conditions of each subject were evaluated.

Results: Four weeks of usage of this cleansing oil significantly decreased skin dryness, scaling, irritation, erythema, and itchiness. Higher improvements were observed for subjects who had previously used cleansers with less cleansing ability. Accompanying those improvements, a significant increase in moisture-retention ability and a significant decrease in transepidermal water loss were observed.

Conclusion: These results suggest that many AD patients cleanse their face with hard rubbing of their skin because of the low cleansing ability of their skin cleansers and may worsen their AD skin symptoms without realizing it.
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http://dx.doi.org/10.1111/jocd.13777DOI Listing
June 2021

Swine multifocal ulcerative colitis and crypt abscesses associated with Entamoeba polecki subtype 3 and Salmonella Typhimurium.

J Vet Med Sci 2020 Apr 26;82(4):463-466. Epub 2020 Feb 26.

Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-oraikita, Izumisano, Osaka 598-8531, Japan.

Piglets aged approximately 50 days exhibited diarrhea and wasting. Multiple white foci were detected in the colon of a dead piglet; histopathological findings revealed multifocal ulcers and crypt abscesses with Entamoeba trophozoites and gram-negative bacilli in the piglet. These pathogens were identified as Entamoeba polecki subtype 3 and Salmonella enterica serovar Typhimurium, respectively. Numerous E. polecki subtype 3 trophozoites were located on the edge of the ulcerative and necrotic lesions in the lamina propria. Crypt abscesses were associated with S. Typhimurium. These results suggest that E. polecki subtype 3 caused multifocal ulcerative colitis accompanied by crypt abscesses with S. Typhimurium in the piglet. This study is the first report of colitis with E. polecki subtype 3 and S. Typhimurium coinfection.
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http://dx.doi.org/10.1292/jvms.19-0682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192718PMC
April 2020

Pathological and virological analysis of concurrent disease of chicken anemia virus infection and infectious bronchitis in Japanese native chicks.

J Vet Med Sci 2020 Apr 20;82(4):422-430. Epub 2020 Feb 20.

National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856, Japan.

A concurrent infection of chicken anemia virus (CAV) and infectious bronchitis virus (IBV) was detected in Japanese native chicks in 2017, in which a high mortality rate (97.7%) was recorded in a small flock of 130 chicks exhibiting poor growth. Histological examination revealed that the affected chicks exhibited two different pathological entities: one was severe hematopoietic and lymphocytic depletion with abnormally large cells containing intranuclear inclusion bodies of CAV, whereas the other was renal tubular necrosis due to IBV infection. Immunohistochemistry detected CAV antigens in the bone marrow, liver, and spleen as well as IBV antigens in the kidneys, trachea, and air sacs. CAV was isolated from the liver sample of the chicks, and the isolated strain was designated as CAV/Japan/HS1/17. A phylogenetic analysis of the CAV VP1 gene revealed that CAV/Japan/HS1/17 is genetically similar to Chinese strains collected from 2014 to 2016. An experimental infection was performed using CAV/Japan/HS1/17 and specific-pathogen-free chicks to determine the pathogenicity of CAV/Japan/HS1/17. The isolate caused 100% anemia and 70% mortality to chicks inoculated at one day old, 80% of chicks inoculated at seven days old also developed anemia, and 10% died from CAV infection. These results suggest that the unusually high mortality in Japanese native chicks can be attributed to dual infection with both CAV and IBV. The results of the experimental infection suggest that CAV/Japan/HS1/17 has a pathogenic potential to specific-pathogen-free chicks and a relatively higher pathogenicity than previous Japanese CAV strains.
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http://dx.doi.org/10.1292/jvms.20-0006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192730PMC
April 2020

Risk Factors and Prognostic Factors of Hearing Impairment in Neonatal Intensive Care Unit-Treated Infants.

Audiol Neurootol 2019 27;24(2):84-89. Epub 2019 May 27.

Department of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Background: Infants admitted to the neonatal intensive care unit (NICU) have a higher incidence of congenital hearing loss compared with the healthy newborn population.

Objectives: To clarify the relationship between risk factors for hearing impairment in NICU-treated infants and deterioration of the auditory brainstem response (ABR) threshold during childhood.

Method: We screened 1,071 high-risk infants admitted to the NICU for hearing impairment. One-hundred forty-eight infants exhibited an abnormal ABR threshold of ≥40 dB nHL. We analyzed the correlation of change in ABR threshold with risk factors for future hearing impairment.

Results: Among infants treated in the NICU, 148 (13.8%) exhibited an ABR threshold of ≥40 dB nHL; 107 of these 148 (72.3%) showed hearing change in the process (102 showed improvement to normal hearing level, whereas 5 showed further deterioration). Our analysis showed that the factors contributing to the elevation of ABR threshold were oxygen administration and chromosomal aberrations.

Conclusions: Factors related to the elevation of ABR threshold were oxygen administration and the presence of chromosomal aberrations. Awareness of risk factors that are more likely to cause hearing loss in infants may aid in follow-up treatment of these children.
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http://dx.doi.org/10.1159/000500316DOI Listing
April 2020

Hyperbaric Oxygen Therapy as Concurrent Treatment with Systemic Steroids for Idiopathic Sudden Sensorineural Hearing Loss: A Comparison of Three Different Steroid Treatments.

Audiol Neurootol 2018 9;23(3):145-151. Epub 2018 Oct 9.

Department of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

We analyzed 356 patients with idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy and systemic steroids (n = 161), systemic steroids alone (n = 160), or intratympanic and systemic steroids (n = 35). The main outcome measure was the hearing recovery rate. The effect of other variables, including the initial averaged 5-frequency hearing level, patient age, interval between the onset of symptoms and treatment, presence of vertigo as a complication, presence of diabetes mellitus, smoking history, and presence of hypertension, on the hearing recovery rate was also evaluated. The overall hearing recovery rate was significantly higher for the patients treated with hyperbaric oxygen therapy and systemic steroids than for those treated with systemic steroids alone (p < 0.001) or systemic and intratympanic steroids (p < 0.001). The presence of vertigo negatively affected hearing recovery. Our findings suggest that hyperbaric oxygen therapy confers a significant additional therapeutic benefit when used in combination with steroid therapy for idiopathic sudden sensorineural hearing loss.
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http://dx.doi.org/10.1159/000493083DOI Listing
October 2019

Immunohistochemical localization of megalin and cubilin in the human inner ear.

Brain Res 2018 12 12;1701:153-160. Epub 2018 Sep 12.

Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, United States. Electronic address:

Megalin and cubilin are endocytic receptors expressed in many absorptive polarized epithelia. These receptors have been implicated in the transport of gentamicin in the inner ear as possible contributors to ototoxic damage. Megalin and cubilin have been characterized in detail in the mouse and rat inner ear, but not in the human inner ear. In this study, megalin and cubilin were localized by immunohistochemistry using affinity-purified antibodies in formalin fixed frozen cryostat and celloidin embedded sections of the human inner ear. In the cochlea megalin and cubilin were localized in marginal cells of the stria vascularis, epithelial cells of the spiral prominence and the Reissner's membrane. In the macula utricle and cristae ampullaris, megalin and cubilin were localized in transitional and dark cells, but not in vestibular hair cells and supporting cells. In the endolymphatic duct megalin and cubilin were localized in the epithelial cells. The localization of megalin and cubilin in the human inner ear is consistent with previous reports in the inner ear of animal models and suggest that these receptors may play an important role in the inner ear endocytic transport, and maybe potential targets for prevention of ototoxic damage or the delivery of medications.
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http://dx.doi.org/10.1016/j.brainres.2018.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289768PMC
December 2018

Trough-Shaped Audiograms Are Common in Patients with Acoustic Neuroma and Sudden Sensorineural Hearing Loss.

Audiol Neurootol 2018 18;23(1):58-62. Epub 2018 Jul 18.

Department of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Acoustic neuroma sometimes presents with sudden-onset sensorineural hearing loss as a primary symptom. We investigated 848 untreated cases that included 20 cases with acoustic neuroma with sudden-onset sensorineural hearing loss and 828 cases without acoustic neuroma. Fourteen of the 20 acoustic neuroma and 90 of the 828 cases of sudden-onset sensorineural hearing loss showed a trough-shaped audiogram with the greatest amount of hearing loss in the mid-frequency range. The incidence of a trough-shaped audiogram was significantly higher in patients with acoustic neuroma than in those without (p < 0.01). This study suggests that a trough audiogram is a significant finding in patients with sudden-onset sensorineural hearing loss and indicates the presence of acoustic neuroma.
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http://dx.doi.org/10.1159/000490233DOI Listing
May 2019

Immunohistochemical localization of Nrf2 in the human cochlea.

Brain Res 2018 12 5;1700:1-8. Epub 2018 Jul 5.

Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, USA. Electronic address:

Oxidative stress plays an important role in several inner ear diseases and normal aging. Nuclear (erythroid-derived 2)-like 2, also known as Nrf2, is a transcription factor encoded by the NFE2L2 gene that controls the expression of genes necessary to reduce oxidative stress. There are no studies to the date on the localization of Nrf2 in the human inner ear in normal or pathological conditions. Therefore, we investigated the immunohistochemical localization of Nrf2 in the human cochlea and vestibule using formalin-fixed celloidin-embedded human temporal bone sections. Nrf2 immunoreactivity (IR) was found in the inner and outer hair cells and supporting cells of the organ of Corti throughout the cochlea. Nfr2-IR was also found in hair cells and supporting cells of the maculae and cristae vestibular sensory epithelia. Nrf2-IR was decreased in the organ of Corti of older age individuals. The immunolocalization of Nrf2 in both auditory and vestibular sensory epithelia suggest that this transcription factor may play a relevant role in protecting sensory hair cells from oxidative stress.
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http://dx.doi.org/10.1016/j.brainres.2018.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231984PMC
December 2018

A case of improved hearing with cochlear implantation in Gaucher disease type 1.

Auris Nasus Larynx 2018 Jun 22;45(3):603-607. Epub 2017 Jun 22.

Department of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.

Gaucher disease is a lysosomal storage disorder that is caused by congenital defective function of the enzyme glucocerebrosidase. Glucocerebroside that is not hydrolyzed by glucocerebrosidase mainly accumulates in the reticular tissue. We describe a Japanese boy with Gaucher disease type 1 who developed bilateral profound sensorineural hearing loss within approximately 4years. We performed cochlear implantation initially on his right ear and again on his left ear 5 months later. The cochlear implants were successfully utilized with a speech discrimination score of 95% on a Japanese sentence recognition test. There are many reports of central hearing loss in Gaucher disease type 2 or 3. However, to the best of our knowledge, this is the first report of profound inner ear hearing loss with Gaucher disease. It also appears to be the first record of cochlear implantation for Gaucher disease. Cochlear implants may be useful for sensorineural hearing loss in patients with Gaucher disease without neurological symptoms other than hearing loss.
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http://dx.doi.org/10.1016/j.anl.2017.05.013DOI Listing
June 2018

Hyperbaric Oxygen Therapy as Adjuvant Treatment for Idiopathic Sudden Sensorineural Hearing Loss after Failure of Systemic Steroids.

Audiol Neurootol 2017 20;22(1):9-14. Epub 2017 Apr 20.

Department of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

We evaluated the outcomes of and prognostic factors for idiopathic sudden sensorineural hearing loss (ISSNHL) treated with adjuvant hyperbaric oxygen therapy (HBOT). A retrospective review of clinical data was performed for 167 patients with ISSNHL who failed to respond to systemic steroids and were treated by adjuvant HBOT at Shizuoka Saiseikai General Hospital. We analysed the clinical outcomes, the averaged 5-frequency hearing level after systemic steroids, patient age, the interval between post-steroids and pre-HBOT, vertigo as a complication, the presence of diabetes mellitus, smoking history, and hypertension. Overall, after HBOT, complete recovery occurred in 16 (9.6%) of the patients, with definite improvement in 16 (9.6%) and slight improvement in 45 (26.9%). The overall rate of hearing improvement was higher in the study group (77/167 cases, 46.1%) than in the control group (52/160 cases, 32.5%; p = 0.021). If performed appropriately, HBOT should be able to improve hearing in many cases unresponsive to initial therapy.
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http://dx.doi.org/10.1159/000464096DOI Listing
September 2018

Facial nerve stimulation following cochlear implantation for X-linked stapes gusher syndrome leading to identification of a novel POU3F4 mutation.

Int J Pediatr Otorhinolaryngol 2016 Dec 6;91:121-123. Epub 2016 Oct 6.

Department of Head and Neck Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. Electronic address:

We report a case of a nine-year-old male who presented with facial nerve stimulation four years after cochlear implantation. Computed tomography was performed revealing a dilated internal auditory meatus and the cochlear implant electrode was found to be protruding into the fallopian canal at the level of the geniculate ganglion. Subsequent genetic analysis demonstrated X-linked deafness type 2 (DFNX2) caused by a novel c.769C > T nucleotide change in the POU domain, class 3, transcription factor 4 gene (POU3F4). Inactivation of electrodes 1 and 19-21 successfully abated facial nerve stimulation.
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http://dx.doi.org/10.1016/j.ijporl.2016.10.003DOI Listing
December 2016

Erratum to: Immunohistochemical techniques for the human inner ear.

Histochem Cell Biol 2016 Oct;146(4):389

Head and Neck Surgery Department, David Geffen School of Medicine at UCLA, 951794, 35-64 Rehab, 1000 Veteran Avenue, Los Angeles, CA, 90095, USA.

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http://dx.doi.org/10.1007/s00418-016-1491-yDOI Listing
October 2016

Immunohistochemical techniques for the human inner ear.

Histochem Cell Biol 2016 Oct 1;146(4):367-87. Epub 2016 Aug 1.

Head and Neck Surgery Department, David Geffen School of Medicine at UCLA, 951794, 35-64 Rehab, 1000 Veteran Avenue, Los Angeles, CA, 90095, USA.

In this review, we provide a description of the recent methods used for immunohistochemical staining of the human inner ear using formalin-fixed frozen, paraffin and celloidin-embedded sections. We also show the application of these immunohistochemical methods in auditory and vestibular endorgans microdissected from the human temporal bone. We compare the advantages and disadvantages of immunohistochemistry (IHC) in the different types of embedding media. IHC in frozen and paraffin-embedded sections yields a robust immunoreactive signal. Both frozen and paraffin sections would be the best alternative in the case where celloidin-embedding technique is not available. IHC in whole endorgans yields excellent results and can be used when desiring to detect regional variations of protein expression in the sensory epithelia. One advantage of microdissection is that the tissue is processed immediately and IHC can be made within 1 week of temporal bone collection. A second advantage of microdissection is the excellent preservation of both morphology and antigenicity. Using celloidin-embedded inner ear sections, we were able to detect several antigens by IHC and immunofluorescence using antigen retrieval methods. These techniques, previously applied only in animal models, allow for the study of numerous important proteins expressed in the human temporal bone potentially opening up a new field for future human inner ear research.
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http://dx.doi.org/10.1007/s00418-016-1471-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444466PMC
October 2016

Neuroglobin immunoreactivity in the human cochlea.

Brain Res 2016 Jan 7;1630:56-63. Epub 2015 Nov 7.

Department of Head and Neck Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095-1624, USA. Electronic address:

Neuroglobin (Ngb) is an oxygen-binding protein with a demonstrated role in endogenous neuroprotective mechanisms. It has been shown to function as a scavenger for reactive oxidizing species thereby assisting in cellular defense against oxidative stress. In the present study, we characterized the presence of Ngb in the human cochlea. Immunohistochemical staining was performed on formalin fixed celloidin human cochlea sections obtained from human temporal bones, using affinity purified polyclonal antibodies against Ngb. Thirty-six temporal bones were analyzed, 15 with normal otologic histories and 21 diagnosed with different inner ear pathologies. Ngb immunoreactivity (Ngb-IR) was consistently expressed in the neurons of spiral ganglia (SG) and supporting cells of the organ of Corti. There was a significant decrease of Ngb-IR in SGNs from specimens with inner ear pathologies when compared to normal specimens. In contrast, Ngb-IR in the organ of Corti did not show significant changes between pathological and normal specimens. The differential pattern of Ngb expression in these cochlear structures suggests that Ngb may participate in defense mechanisms in inner ear pathologies where oxidative stress is involved.
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http://dx.doi.org/10.1016/j.brainres.2015.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966546PMC
January 2016

Relationship between tympanic membrane retraction and habitual sniffing in patients with cholesteatoma.

Acta Otolaryngol 2013 Oct;133(10):1030-4

Department of Otorhinolaryngology/Head & Neck Surgery, Hamamatsu University School of Medicine , Hamamatsu, Shizuoka.

Conclusion: Habitual sniffing affects the pathogenicity and recurrence of cholesteatoma. Postoperative instructions requesting patients to cease sniffing may reduce the retraction and recurrence of cholesteatoma.

Objective: To examine the relationship between tympanic membrane retraction and habitual sniffing in patients with cholesteatoma.

Methods: We recruited 98 patients (102 ears) who were surgically treated for cholesteatoma by canal wall-down tympanoplasty (22 ears) or canal wall-down tympanoplasty with reconstruction methods (80 ears). We classified these patients into two groups on the basis of their preoperative habitual sniffing: habitual and non-habitual sniffers. The findings of the contralateral tympanic membrane were examined in each group and were classified according to the Tos classifications. Next, we evaluated the incidence of 1-year postoperative tympanic membrane retraction treated by the canal-down tympanoplasty with reconstruction method in the following three groups: non-habitual sniffing group, sniffing cessation group, and continual sniffing group.

Results: In habitual sniffers, the Tos classifications of contralateral tympanic membrane were normal in 7% (3/41). In contrast, for non-habitual sniffers, the findings were normal in 39% (21/54). These results indicate that sniffing causes tympanic membrane retraction. The tympanic membranes of patients in the sniffing cessation group were largely normal after surgery. However, more than 50% of the patients who continued to sniff after surgery showed retraction or recurrent cholesteatoma.
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http://dx.doi.org/10.3109/00016489.2013.808763DOI Listing
October 2013

Congenital middle ear cholesteatoma: experience from 26 surgical cases.

Ann Otol Rhinol Laryngol 2013 May;122(5):316-21

Department of Otorhinolaryngology-Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Objectives: We analyzed the clinical features and surgical techniques used in cases of childhood congenital cholesteatoma of the middle ear.

Methods: We studied 26 patients (26 ears) who underwent surgery for congenital cholesteatoma between January 1998 and December 2009, focusing on the location and type of cholesteatoma, the surgical procedures involved, and the results obtained. Patients with prior otologic procedures were excluded. A 4-stage system was used to grade the cholesteatomas.

Results: The frequency of posterior-quadrant involvement and open-type cholesteatomas increased in the more advanced stages. Second-look operations were performed in 60% of stage III and 75% of stage IV cases; and residual cholesteatomas were found in 20% of stage III and 75% of stage IV cases. Of the cases evaluated both before and after the operation, 100% of stage I and II cases, 86% of stage III cases, and 50% of stage IV cases showed improvement in hearing function.

Conclusions: The staging system is relatively simple, while accurately reflecting clinical results. However, there are many differences between the anterior and posterior types of congenital cholesteatomas in surgical approach and postoperative progression that are not reflected in the classification systems and require further study. In addition, we reviewed the surgical procedures involved in anterior-quadrant cases, and propose a modified surgical procedure.
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http://dx.doi.org/10.1177/000348941312200505DOI Listing
May 2013

Surgical approach for treatment of carcinoma of the anterior wall of the external auditory canal.

Otol Neurotol 2012 Apr;33(3):450-4

Department of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Objective: Treatment outcomes for carcinomas of the external auditory canal (EAC) were evaluated regarding radiologic and pathologic factors.

Study Design: Retrospective case review.

Setting: University hospital.

Patients: Fifteen patients histologically diagnosed with carcinomas of the EAC.

Intervention: A radiologic and pathologic analysis was performed on these patients histologically diagnosed with carcinomas of the EAC and treated surgically at our institution. We evaluated the size of focal defects in the anteroinferior (AI) canal wall of the tympanic bone with preoperative computed tomographic (CT) scans. Histopathologic slides for the same patients were evaluated according to the same criteria as the CT scans.

Main Outcome Measure: Pathologic features and estimated survival rate.

Results: Preoperative CT scans of 15 temporal bones demonstrated an AI canal wall defect ranging from less than 1 mm to full-thickness destruction. Six of 15 patients had an AI canal wall defect greater than 2 mm on preoperative CT scan. Pathologic findings in these 6 cases showed extension of the tumor through the AI defect into the anterior soft tissues. Information on patients' survival status was obtained after a median follow-up period of 78.3 months (range, 18-151 mo).

Conclusion: Preoperative CT can be used to accurately determine the pathologic extent of tumor invasion in carcinomas of the EAC. This diagnostic method facilitates exchange of accurate clinical data in a comparable form and can be used to evaluate the efficacy of existing and proposed treatments for EAC tumors.
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http://dx.doi.org/10.1097/MAO.0b013e318245ccbfDOI Listing
April 2012

[Surgical indications and approaches for parapharyngeal space tumors].

Nihon Jibiinkoka Gakkai Kaiho 2011 Oct;114(10):807-13

Department of Otolaryngology, Hamamatsu University School of Medicine, Hamamatsu.

In the 20-years from 1991 to 2010, we pathologically diagnosed 24 subjects with parapharyngeal space tumors by biopsying and/or resecting of 24 tumors. Of these, 18 were benign and 6 malignant. Pleomorphic adenoma and schwannoma predominated, accounting for 7 cases each. Enhanced CT and MRI were very useful in diagnosis, judging involvement and localization, and assessing radiological and pathological tumor diagnosis. Important radiological factors are determining whether tumor origin is pre-or post-styloid, and how the tumor is enhanced in CT or MRI. We treated 15 subjects surgically, telling 9 the diagnosis, and used only biopsy or scans. It is vital in follow-up to determine long-term treatment response.
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http://dx.doi.org/10.3950/jibiinkoka.114.807DOI Listing
October 2011

Role of granulosa and theca cell interactions in ovarian follicular maturation.

Microsc Res Tech 2006 Jun;69(6):450-8

Department of Obstetrics and Gynecology, Fukui Medical University, Yoshida-gun, Fukui 910-1193, Japan.

We developed a culture system in which two types of ovarian follicular cells were allowed to attach to opposite sides of a collagen membrane. Using this in vitro cell culture system, we studied the effects of granulosa- and theca-cell interaction on the morphology, structure, and function of bovine ovarian follicular cells. In the first part of the study, we explored how the interaction between theca and granulosa cells affects the morphology and structure of the cells. This study was done using follicular cells collected from bovine ovarian follicles at the early developmental stage. Granulosa cells cultured alone were flattened, and formed a monolayer sheet. By contrast, granulosa cells cultured with theca cells were convex, and formed multilayer sheets. Theca cells cultured alone were thin, flat, and spindle-shaped. Theca cells cultured with granulosa cells were also spindle-shaped; however, they appeared convex and more densely packed when compared with theca cells cultured alone. In the second part of the study, the possible role of the cellular interaction in the control of differentiation and growth of granulosa and theca cells was investigated. When follicular cells were isolated from the early stage of follicular development, theca cells reduced progesterone and inhibin production by granulosa cells and augmented the growth of granulosa cells. When the cells were isolated from the late stage of follicular development, by contrast, theca cells augmented hormonal production by granulosa cells, and did not affect the growth of granulosa cells. The growth and androstenedione production by theca cells were increased by the presence of granulosa cells, irrespective of the origin of follicular cells. These results demonstrated that communication between two types of follicular cells results in reciprocal modulation of their morphology, structure, growth, and function. Cellular interactions seem to be one of the major factors controlling the differentiation and growth of the follicular cells during the follicular maturation process. In contrast to granulosa and theca cells cultured alone, cells in the coculture seemed to possess morphological and functional characteristics more similar to those of cells in the growing follicular wall in vivo. Thus, we speculate that the interaction between these two types of follicular cells is essential for the maintenance of original structure and function of the bovine follicular wall.
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http://dx.doi.org/10.1002/jemt.20304DOI Listing
June 2006

Phosphodiesterase inhibitors as anti-cancer drugs.

Biochem Pharmacol 2004 Sep;68(6):981-8

Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.

It is well known that high intracellular levels of cAMP can effectively kill cancer cells in vitro. Unfortunately substances elevating cAMP such as forskolin, 8-bromo-cAMP, 8-chloro-cAMP, monobutiryl or dibutiryl cAMP are not recommended to be used as anti-cancer drugs because of their high cytotoxicity. In contrast blockers of phosphodieterases such as theophylline and aminophylline, which could elevate intracellular cAMP, are commonly used as anti-asthma drugs reaching concentrations in the blood of 10-20 microg/ml. We tested the effectiveness of theophylline and aminophylline to induce cell death alone or in combination with common anti-cancer drugs such as cisplatin and gemcitabine (gemzar). We examined such drug combinations in the induction of cell death in a variety of carcinoma cell lines derived from human ovarian, prostate and lung cancer and in granulosa cell line transformed by SV40 and Ras oncogene. While theophylline could induce moderate cell death alone, at 20-25 microg/ml concentrations, aminophylline was ineffective at this concentration. Theophylline (at 15-25 ng/ml) was found in all four representative cell lines to synergize with gemcitabine or cisplatin to induce programmed cell death, which permits a reduction in the effective doses of cisplatin and gemcitabine by 2-3-fold. The effect of theophylline in induction of apoptosis involved reduction of intracellular levels of Bcl2. Such a reduction was proportional to the extent of apoptosis induced by theophylline as well as by the combined drug treatments. Therefore, we propose that theophylline should be considered as a potential anti-cancer drug in combination with other chemotherapeutic drugs. Screening of other phosphodiesterase blockers, which are not severely toxic, could open a possibility to improved chemotherapeutic cancer treatments with reduced undesired side-effects. A clinical trial, using theophylline as an anti-cancer drug, is currently being conducted in lung cancer patients.
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http://dx.doi.org/10.1016/j.bcp.2004.05.026DOI Listing
September 2004

Vasoactive and natriuretic mediators in umbilical cord blood: a report of our observation and review of the literature.

Early Hum Dev 2002 Oct;69(1-2):57-64

Department of Pediatrics, Faculty of Medicine, Fukui Medical University, Fukui, Japan.

Background: The relative potency and interrelationship among vasoactive and natriuretic mediators are thought to be important in the transition from fetal to neonatal life. However, little is known about their potential roles in the perinatal setting.

Aim: The aim of this study was to evaluate further the potential roles of vasoactive and natriuretic mediators in the perinatal setting.

Study Design: We measured umbilical venous levels of arginine vasopressin, endothelin-1, adrenomedullin, natriuretic peptides and NO(2)(-)/NO(3)(-) in 24 vaginally delivered newborns and examined their possible functions.

Results: Cord levels of vasopressin, endothelin-1 and adrenomedullin were considerably higher compared with normal adult values; the concentrations were more than 10-fold higher for vasopressin, and more than threefold higher for endothelin-1 and adrenomedullin. The levels of natriuretic peptides and NO(2)(-)/NO(3)(-) were almost comparable to those of normal adults. Among the mediators, there was a significant correlation between endothelin-1 and adrenomedullin.

Conclusions: It appears from other studies that the postnatal fall in vasopressin and endothelin-1 levels is associated with increased levels of natriuretic peptides and NO(2)(-)/NO(3)(-). Based on these observations, we consider that these mediators may play active roles in the initiation, maintenance or both of the transition from fetal to neonatal life.
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http://dx.doi.org/10.1016/s0378-3782(02)00038-5DOI Listing
October 2002

Effects of ovarian theca cells on apoptosis and proliferation of granulosa cells: changes during bovine follicular maturation.

Biol Reprod 2002 Jun;66(6):1635-9

Department of Obstetrics and Gynecology, Fukui Medical University, Fukui 910-1193, Japan.

We have investigated the role of theca cells in the control of apoptosis and proliferation of granulosa cells during bovine ovarian follicular development using a coculture system in which granulosa and theca cells were grown on opposite sides of a collagen membrane. A DNA fluorescence flow cytometry was used to determine the extent of apoptosis and proliferation in populations of granulosa cells. When granulosa cells were isolated from small follicles (3-5 mm), the percentage of apoptotic cells gradually increased by 1.8-fold during the 3 days of culture. This change was reduced (3.1-fold) by the presence of theca cells. When the cells were isolated from large follicles (15-18 mm), the percentage of apoptotic granulosa cells was gradually reduced (3.4-fold) during the 3 days of culture in single-cultured groups. The percentage of apoptosis on Day 1 was reduced (1.6-fold) by the presence of theca cells. However, such an effect was not detected on Days 2 and 3 of the culture. Theca cells did not affect the proliferation of granulosa cells obtained from either small or large follicles. The present study suggests that theca cells regulate the fate of granulosa cells throughout the follicular maturation process by secreting factors that suppress apoptosis.
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http://dx.doi.org/10.1095/biolreprod66.6.1635DOI Listing
June 2002