We are focusing on the histamine H₁ receptor (H1R) as an allergic disease-sensitive gene. H1R is a rate-limiting molecule of the H1R signal because the signal is increased with elevated receptor expression levels. We discovered that the direct stimulation of H1R induced the up-regulation of H1R gene expression through PKCδ activation. The mechanism of H1R gene expression was revealed to play a key role in the receptor expression level in studies using cultured HeLa cells and allergic rhinitis model rats. Antihistamines have three effects: the blocking effect on histamine signaling of H1 receptors; the suppressive effect on histamine-induced up-regulation of H1R mRNA that is the transcriptional activation of H1R; and the suppressive effect on H1R mRNA in the absence of histamine that is the basal transcription of H1R. The third effect may be another side of the inverse agonist action of antihistamine. We demonstrated that repeated pretreatment with antihistamines in the allergic rhinitis model rats resulted not only in the improvement of symptoms but also in the suppression of the up-regulation of H1R mRNA in the nasal mucosa. We next investigated the effect of preseasonal prophylactic treatment with antihistamines on nasal symptoms and the expression of H1R mRNA of the nasal mucosa in patients with cedar pollen pollinosis. During the peak pollen period, the expression of H1R mRNA in the nasal mucosa and the scores of sneezing and watery rhinorrhea in patients receiving preseasonal prophylactic treatment with antihistamines were significantly suppressed in comparison with those in the patients without treatment. These results suggest that H1R is an allergic disease-sensitive gene and H1R plays an important role in allergic rhinitis through the regulation of histamine signaling.

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We report herein on the 20th case in Japan of a carcinoid tumor observed in the middle ear. The patient was a 71-year-old man who was first seen in our hospital in November 2012 for tinnitus of 3 years’ duration. On otoscopic examination, a white mass could be observed through the tympanic membrane. High computed tomography demonstrated a tumor like lesion with no evidence of bone destruction. We first performed a probe tympanotomy and pathologically the lesion was diagnosed as a carcinoid tumor of the middle ear. We subsequently performed a tympanoplasty and completely removed the tumor. Recently, somatostatin receptor imaging has become available to detect metastasis or recurrence of carcinoid tumors. We think somatostatin receptor imaging may be appropriate for assessing carcinoid tumors of the middle ear.

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Eosinophilic otitis media is characterized by otorrhea of the glue state with infiltration of many eosinophils in otorrhea and in many cases is considered as intractable otitis media in which bronchial asthma and sinusitis are merged. Between 2003 and 2010, we diagnosed 7 patients as having eosinophilic otitis media and studied their clinical course which is presented herein. We treated 1 case surgically and treated 6 cases conservatively. The clinical course of the case which was treated surgically is good at present in respect of the aspect of the eardrum and hearing ability progress. Hearing ability got worse in 2 cases among the 6 cases treated conservatively and in 1 case we could not perform systemic administration of steroids because of the patient’s medical disease. Eosinophilic otitis media is considered as intractable otitis media, but our experience suggested that we can prevent advance of hearing loss as much as possible in those cases where we can grasp the condition of the disease exactly and treat patients appropriately according to their morbidity.

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A 28-year-old man presented with progressive right hearing loss from a year previously. He had suffered from left hearing loss since his junior high school days. He received medication from other clinic but his symptom was not improved. He visited Kyoto University hospital when he was 27 years old. He had right mixed hearing impairment with 51.7 dB of air conduction hearing level, 20 dB of air-bone gap, and no stapedial muscle reflex. Blue sclera was noted and the patient had a history of osteogenesis imperfecta with several instances of bone fractures. CT scan showed demineralization in the bilateral cochleae and vestibules. We made the diagnosis of van der Hoeve Syndrome based on these clinical symptoms, signs, and examinations. A small fenestration stapedectomy was attempted in his right ear but the footplate was fractured. A partial stapedectomy was performed with removal of the posterior half of the footplate. The averaged improvement for air conduction hearing level was 31.7 dB and the air-bone gap was 10 dB even two years after the surgery. This case suggests that stapedectomy for van der Hoeve syndrome is useful if it is carefully performed.

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A 66-year-old man consulted our clinic complaining of fullness in both ears during hospitalization for pyogenic spondylitis at the Department of Internal Medicine in our hospital. He had been diagnosed as having myasthenia gravis 13 years previously and had been suffering from nephritic syndrome and steroidogenic psychosis for eight years. We applied transnasal tympanic inflation using a eustachian catheter (catheter inflation) because otitis media with effusion was observed in both ears. Nothing unusual was observed at the first application except the insufflation to both ears sounded stenotic. However, cervical and mediastinal emphysema suddenly developed at the second application. The patient’s general condition and state of consciousness were not affected just after the onset. Fortunately he recovered during an eight-day observation period with no additional treatment, for antibiotics had already been prescribed for pyogenic spondylitis. How to prevent and how to deal with complications are also discussed in a review of 23 cases with severe complications including fatal cases since 1985 in Japan.

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We report herein on a patient with a bulky nevus cell nevus in the external auditory canal. A 43-year-old woman had a feeling of fullness in the right ear and noticed a tumor in the right external auditory canal. When the patient was first seen, a pedunculated mass lesion located at the base of the entrance to her right external auditory canal was found. As its appearance was skin-colored, it was difficult for us to make a diagnosis of nevus cell nevus at first view. It was diagnosed as a dermal nevus by a dermatologist at our hospital. We decided on the course of treatment after receiving advice from a dermatologist, and removed it surgically. Dermal nevi should be resected because of their potential for malignant change for cases and locations in which careful observation is difficult, such as in the external auditory canal.

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Pyogenic granuloma is a benign tumor that involves the skin and mucosa. It often occurs during pregnancy and the most frequent symptoms are nasal bleeding. The author encountered a case of pyogenic granuloma of the nasal cavity which was resected via the midfacial degloving approach.
A 31-year-old woman, 2 months after delivery of a baby, presented with spontaneous left-sided epistaxis and swelling of the bridge of the nose that had started 1 month previously. Physical examination demonstrated a white and dark-red mass that filled her left nasal cavity. The histological findings showed pyogenic granuloma. We determined to resect the mass because it remained 2 months after delivery without spontaneous regression.
We chose the midfacial degloving approach to gain access to regions of the midface without external incisions. The entire successful resection was possible with this approach, and there has not been any recurrence for 1 year postoperatively. The cosmetic results were excellent and the patient was satisfied. No significant complications were seen.
The midfacial degloving technique can be considered as a valuable procedure with low morbidity and excellent cosmetic outcome. It may be a viable procedure for pyogenic granuloma of the nasal cavity.

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The treatment results of 33 cases with laryngeal granuloma (contact granuloma, 31 cases and intubation granuloma, 2 cases) were evaluated. Five of six operated cases with contact granuloma showed post-operative recurrence. Following acid suppression therapy at bed time and nocturnal anti-reflux precautions, 25 of 30 cases with contact granuloma, and both 2 cases with intubation granuloma, showed resolution of their granuloma. The resolution occurred within 6 months in 76%, and within 1 year in 92% of cases with contact granuloma (between 2 weeks and 144 weeks, mean, 26.6 weeks).

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Mondor's disease is a rare disease characterized by thrombophlebitis of the subcutaneous veins, which mainly occurs in the chest. We report herein on a case of Mondor's disease of the neck. A 30-year-old man complained of a tender mass on his right neck. Physical examination showed folliculitis with a subcutaneous cord-like induration on the neck. Ultrasonographic and CT examinations showed enlargement of a cutaneous vein with a blood clot. The folliculitis and subcutaneous induration disappeared following treatment with oral antibiotics. We thought that the Mondor's disease had developed from the folliculitis. Most of the patients with Mondor's disease recover with conservative treatment within a few months. Therefore, we should bear this disease in mind when we examine patients with painful subcutaneous cord-like indurations on the neck.

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Three months beforehand, a 13-year-old boy had a strange feeling in his left submandibular area.
However, since there was neither a fever nor pain, he adopted a wait-and-see attitude.
He noticed a swelling of the left submandibular area about one month prior to presenting at our department, and he came for a checkup.
In the initial examination, although neither fever nor pain was present, we found a palpable hard lesion in his left submandibular area.
A blood examination showed a WBC count of 7400 and a CRP level of 0.62. Under the diagnosis of a suspected submandibular inflammatory lesion of some kind, we started oral antibiotic (CFPN), and scheduled a further examinaiton after CT imaging.
On the following day, the swelling of his lesion increased, and we examined him again 3 days after that.
The enhanced CT imaging showed an extensive inflammatory lesion with abscess formation in the lesion.
We hospitalized him that day and we started antibiotics (FMOX+CLDM) via intravenous drip infusion.
We conducted the enhanced CT imaging again on the 7^th day of hospitalization, but despite the antibiotics the abscess had not improved. We performed abscess drainage under local anesthesia, and inserted a penrose drain.
We conducted laboratory culture of the pus and continued intravenous drip infusion (CFPN+CLDM).
On the 15^th day, the culture result showed non-tubercular anti-acid fungal infection, and we changed the antibiotic (LVFX) to oral administration based on the drug sensitivity test result.
The patient had the drain tube extracted on the 26^th day, and he left hospital on the 30^nd post-admission day.
After that, we continued oral antibiotics (STFX) on an outpatient basis.
The swelling of his lesion improved and the operative incision had healed four months after leaving the hospital.
About seven months after leaving the hospital, full recovery from the pathology was seen on CT and MRI imaging, and we stopped the medication.

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Flourens’s two reports (1828) on the sections of semicircular canals in birds and mammals were first introduced which afforded the peculiar phenomen. The section of the one semicircular canal was consistently followed by a movement along the plane delineated by the semicircular canal. The nerve fibers from each semicircular canal ended at the corresponding cerebellar pedunculi. The section of a peduncle gave rise to a peculiar phenomenon corresponding to the nerve fibers coming from the semicircular canal of which the section showed a similar peculiar phenomenon. Flourens thus concluded that the energy and coordination of the semicircular canal originated from the cerebellum. Flourens stated that the phenomena seen in sections of semicircular canals were associated with various maladies of both human and animal as important symptoms. Flourens also stated that the results of his experiments would contribute to the progress in diagnoses, treatments and in defining the origins of the maladies. This statement proceeded Menière’s similar statement by more than 30 years.

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