Topographical relationships among the facial nerve, chorda tympani nerve and round window with special reference to the approach route for cochlear implant surgery.

The topographical relationships among the facial nerve (FN), chorda tympani nerve (CT), and round window (RW) in 22 temporal bone specimens were analyzed morphometrically in order to examine which route is widest through the facial recess between the FN and CT during cochlear implant surgery and in order to establish some criteria to assist in the evaluation of the best surgical approach. Two lines, i.e., the FN-RW line and CT-RW line, were speculated as limitations of a visual field for this surgery. According to the relative position of these structures, including the posterior wall of the external auditory canal (EAC) and an inserted pin-gage that indicates the hypothetical widest approach route, the relationships were classified into five types. Most frequently, the widest approach route through the facial recess did not point directly at the RW, but at the basal turn at the promontory. Moreover, this approach route crossed the FN-RW line in a posterior to anterior direction and the CT-RW line frequently crossed the posterior wall of the EAC. The latter seemed to provide a critical landmark for avoiding damage to the CT during cochlear implant surgery. Therefore, we recommend inserting the electrode into the basal turn.

Morphometric study of the medial aspect of the human maxillary sinus with special reference to the nasal fontanelle.

OBJECTIVE: The purpose of this study was to clarify configurations of the nasal fontanelle (NF) from the morphometrical point of view, especially variations of its four margins (anterior, posterior, superior, and inferior), for clinical application. METHODS: We used 136 sides of hemi-sectioned heads that were obtained from 119 donated Japanese cadavers (66 men and 53 women with an average age of 77.6+/-12.0). After mucosal examination, the specimens were boiled with a small amount of powdered soap and treated with protease. The residual mucous membrane was then gently removed. These specimens were originally made for our previous study describing variations of the uncinate process (Isobe M, Murakami G, Kataura A. Variations of the uncinate process of the lateral nasal wall with clinical implications, Clin. Anat. 1998;11:295-303). Different series of measurements were conducted based on surgical approaches and angles of observation. RESULTS: The superior margin of the NF is difficult to identify because the ethmoidal infundibulum, which leads the anterior end of the margin upward, often interrupts the superior margin. Because the inferior and posterior margins are modified by thin paper-like bony structures and because the anterior margin is disturbed by variations of the lacrimal bone and/or the inferior turbinate, they are also difficult to identify. Knowing these variables, we evaluated the NF morphometrically. The NF was located 12.6+/-4.3 mm posterior to the anterior nasal spine and 6.6+/-2.2 mm anterior to the sphenopalatine foramen. The size of the NF was 17.9+/-3.2 mm (anteroposterior axis) x 11.5+/-3.0 mm (inferosuperior axis). The lowest orbital floor was located 10 mm below the superior margin of the anterior NF (-10 mm), and the distance was therefore measured as -3.7+/-2.4 mm on average. Viewed from the maxillary sinus, the location of the NF varied along the anteroposterior axis, whereas it was located consistently at the most superior portion of the medial aspect of the sinus wall. CONCLUSION: During endoscopic sinus surgery for tumor resection in the maxillary sinus, a large and primary window should be prepared in the posterior NF, including partial removal of the uncinate process. Preparation of an additional window in the inferior meatus is preferable to enlargement of the primary window. Approaching the anterior NF should be avoided, if possible, due to its complicated configuration as well as its proximity to the orbital floor.

Relationship between infiltrating cells and adhesion molecules in the nasal mucosa of patients with allergic rhinitis.

Antigen-induced changes of cell adhesion molecules and their relationships to infiltrating cells were investigated immunohistochemically in nasal mucosa of perennial allergic rhinitis patients. An increased expression of E-selectin and VCAM-1 was noted on the vascular endothelium of the nasal mucosa 15-25 h after the topical antigen challenge. Although there was no increased expression of ICAM-1, we noted a positive correlation between the expression of E-selectin and ICAM-1. The expression of E-selectin and VCAM-1 as well as ICAM-1 was revealed to be correlated with the number of EG2-positive cells and CD4-positive cells, but not with elastase-positive cells. These findings suggest that all these adhesion molecules play a role in the topical influxes of eosinophils and CD4-positive cells in allergic nasal mucosa.

[A relationship between birch pollen and meteorological factors during the past four years and pollen survey in Sapporo in 1997].

It is well known that grass pollinosis has been the most representative pollinosis in Hokkaido prefecture, Japan, However, it is also well known that birch (Japanese white birch, Betula platyphylla var. japonica) pollinosis is gradually increasing, which is marked especially in Sapporo and its neighborhood. We analyzed a relationship between the birch pollen count and meteorological factors statistically. Moreover, the principal airborne pollen counts in Sapporo in 1997 were assessed and compared with the previous pollen data. As a results of this study, it was showed a close relationship between the annual amounts of birch pollen and meterological factors of the year before, especially in May and June might be important. Moreover, there is a strong negative correlation between the birch pollen count and humidity, which seems to affect bringing up flower buds. As for the principal airborne pollen counts, some kinds of tree pollen, including birch pollen, were observed from the end of March, followed by grass (Gramineae) pollen in June and mugwort (Artemisia) pollen from the end of August, respectively. The annual amounts of grass pollen showed a decreasing trend.

Anomalous vessels in the middle ear associated with congenital anomalies of the internal carotid artery.

A case with unilateral hypoplasia of the internal carotid artery was reported. The rerouting of anomalous vessels in the middle ear, visualized by otoscopy, was demonstrated with CT and MRI. Associations with internal carotid hypoplasia, the intercarotid collaterals, both anomalous middle ear arteries and the enlarged internal maxillary artery were confirmed with MRI. MR images were helpful to diagnose not only the anomalous vessels but also the multiple anastomoses.

Topical CTLA4-Ig suppresses ongoing mucosal immune response in presensitized murine model of allergic rhinitis.

Allergic rhinitis is thought to be mediated by CD4+ T cells producing Th2-associated cytokines. Optimal Ag-specific T-cell activation requires the engagement of T-cell receptor with antigen (Ag) in the context of MHC, and the engagement of appropriate costimulatory molecules. One of the most well-characterized costimulatory pathways is the interaction of B7/CD28-CTLA4 molecules. Recent studies have suggested that the costimulatory pathway may influence the development of Th2 immune responses. The objective of this study was the examination of the role of B7/CD28-CTLA4 costimulatory pathway in the pathogenesis of ovalbumin (OVA)-induced immune response in presensitized murine model of allergic rhinitis. Systemically presensitized BALB/c mice significantly developed Ag-induced early phase nasal symptoms, nasal hyperresponsiveness to histamine, nasal eosinophilia, serum levels of OVA- specific IgE and Th2-associated cytokines following repeated topical Ag challenges. Topical administration of CTLA4-Ig during nasal challenges inhibited Ag-induced nasal symptoms and histamine hyperresponsiveness. We also found a significant reduction in nasal lavage eosinophilia and serum levels of OVA-specific IgE. Furthermore, CTLA4-Ig treatment significantly decreased interleukin (IL)-4 content in nasal tissue, while there was no significant change in IL-5 or IFN-gamma levels. These results suggest that B7/CD28-CTLA4 costimulatory pathway mediates the development of ongoing Th2 immune responses and plays a major role in regulating allergic disease, such as allergic rhinitis.

[Effects of immunotherapy on cytokine production from peripheral blood mononuclear cells in patient with house dust mite allergic rhinitis].

We studied effects of immunotherapy on mite antigen-induced cytokine production from peripheral blood mononuclear cells in patient with house dust mite allergic rhinitis. In good response group, IL-4 production were lower than that of poor response group. In contrast, IFN-gamma production and the ratio of IFN-gamma to IL-4 synthesis were significant higher than that of poor response group. The production of IFN-gamma significantly correlated with the periods of immunotherapy. These results suggest that the changes of cytokine synthesis have a close relationship to clinical effects of immunotherapy.

Cellular immune response of adenoidal and tonsillar lymphocytes to the P6 outer membrane protein of non-typeable Haemophilus influenzae and its relation to otitis media.

Cellular immune responses to the P6 outer membrane protein of non-typeable Haemophilus influenzae (NTHi) were determined in vitro by measuring immunoglobulin (Ig) secreting cells and lymphocyte proliferation in adenoidal and tonsillar lymphocytes from 19 children. Preliminary tests showed that P6 did not stimulate naive cells such as cord blood lymphocytes, but did stimulate sensitized cells in adenoids and tonsils. Cellular proliferation was significantly higher in adenoidal lymphocytes than in tonsillar lymphocytes (median: quadratile of stimulation index = 3.7:2.3-5.5 vs. 1.2:1.0-2.1, p < 0.02). A comparison between children with or without otitis media revealed that proliferative responses to P6 of adenoidal lymphocytes from children with otitis media were significantly decreased (2.0:1.8-3.6 vs. 3.7:2.3-5.5, p < 0.04). P6-specific antibody secreting cells were identified in a total of 14 adenoids and the number of cells secreting IgA was decreased in the otitis media group compared to controls (median: quadratile/10(6) cells = 435:359-499 vs. 755:593-1870, p < 0.05). Cultivation with P6 stimulated IgA secretion in children without otitis media, while no response was seen in children with otitis media (median: quadratile/10(6) cells = 1323:915-2410 vs. 2240:1900-2830, p < 0.02). These preliminary data demonstrate that lymphocytes from adenoids and tonsils recognize P6 as a specific antigen and that the adenoid is the more reactive of the two organs. Impaired P6-specific cellular immune responses of adenoids in children with otitis media may explain the recurrent nature of otitis media due to NTHi in the otitis prone population.

Increased interleukin-6, interferon-gamma and tumour necrosis factor-alpha production by tonsillar mononuclear cells stimulated with alpha-streptococci in patients with pustulosis palmaris et plantaris.

In vitro cytokine production by tonsillar mononuclear cells under culture conditions with or without lyophilized streptococcal antigens was measured by enzyme-linked immunosorbent assay (ELISA). Under culture conditions without any stimulus, a certain amount of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, and interleukin (IL)-6, was detected in the supernatant culture fluids from all 29 donors tested and just detectable levels of IL-1alpha and IL-2 were identified in 5 of 12 donors tested; but IL-4 and IL-5 were not detected in any supernatants from 21 donors tested. In 16 patients with pustulosis palmaris et plantaris (PPP), all three alpha-streptococcal antigens from Streptococcus, (S.) sanguis, S. salivarius and S. mitis induced production of IL-6. IFN-gamma and TNF-alpha by tonsillar mononuclear cells at a significant level. However, no significant induction of such cytokines by alpha-streptococcal stimulus was seen in 13 donors without PPP. No significant difference in cytokine production by tonsillar mononuclear cells was seen between the PPP and non-PPP subjects, when stimulated with S. pyogenes, Staphylococcus aureus Cowan I and pokeweed mitogen. In the experiments using tonsillar cell subsets, the cytokine inductions by alpha-streptococcal stimulus were found in monocyte-depleted cells as well as in purified T-cells. but not in B-cells. These data suggest that IL-6, IFN-gamma and TNF-alpha may play an important role in immunological reactions in the tonsils and that a hyper-immune response to some of alpha-streptococcal antigens through increased production of such cytokines by tonsillar mononuclear cells, to which T-cells mainly contribute, may play a key role in the pathogenesis of PPP.

Chondrosarcoma of larynx: a case successfully reconstructed after total cricoidectomy.

A case of a 64-year-old male with low-grade chondrosarcoma of the left posterolateral lamina of the cricoid cartilage is reported, in which a total cricoidectomy and partial resection of the left thyroid cartilage were performed. The rest of the thyroid cartilage and the arytenoid mucosa were approximated with sutures to the first tracheal ring, and a silastic T-tube was placed through the tracheostoma as a stent. The postoperative course has been successful except for the existence of a tracheal stoma and slight hoarseness. There has been no evidence of laryngeal stenosis nor recurrence at about 9 years postoperatively.

A case of anaplastic thyroid carcinoma surviving disease free for over 2 years.

A 52-year female presented with an enlarged thyroid mass and lump sensation in the throat. The cytologic examination showed class five and she was admitted to the hospital to undergo operation. Total thyroidectomy was done and the tumoral invasion of the trachea was removed. We performed tracheoplasty using a sternocleidomastoid muscle-clavicle myoosseous flap in a single stage operation. Histologic diagnosis revealed anaplastic thyroid carcinoma After upper mediastinal dissection had been performed, systemic chemotherapy using pirarubicin, cisplatin and etoposide was administered. In addition, she was treated with radiochemotherapy using pirarubicin, cisplatin and a total of 58 Gy was administered. No recurrence of the tumor has been noted since the above operation 2 years ago. Immunohistochemical studies of primary and metastatic tissues in this case revealed a positive expression of p53 protein in both.

[Cytokine production of peripheral mononuclear cells in HD-mite-allergic rhinitis patients].

To elucidate the role of cytokines in the pathogenesis of allergic rhinitis, the proliferative response and cytokine production of peripheral mononuclear cells (PMNC) following stimulation with mite-antigen were evaluated in HD-mite-allergic rhinitis patients (mite-allergy group), non-HD-mite pollinosis patients (non-mite-allergy group) and normal subjects (normal group). The proliferative response of PMNC to PHA stimulation was not different among the groups, whereas that to mite-antigen stimulation was significantly higher in the mite-allergy group than in the normal group. Production of both IL-4 and IL-5 from PMNC after stimulation with mite-antigen was significantly higher in the mite-allergy group than in the normal group. Production of IFN-gamma from PMNC after antigen stimulation was significantly increased in both the mite-allergy and normal groups. The ratio of IFN-gamma to IL-4 synthesis was significantly higher in the normal group than in the mite-allergy group. This study revealed cytokine synthesis from PMNC after the antigen-stimulation was predominantly Th2-cytokines in patients with HD-mite-allergic rhinitis.

Suppressive effects of CTLA4-Ig on nasal allergic reactions in presensitized murine model.

Ag-specific T cell activation requires the engagement of T cell receptor (TCR) with antigen in the context of MHC, and the engagement of appropriate costimulatory molecules. It is well established that B7/CD28-CTLA4 costimulatory pathway plays an important role in the induction of T helper (Th) cells in T-cell dependent immune reactions. In this study, we evaluated the effects of blocking the costimulatory pathway by systemic administration of CTLA4-Ig during repeated nasal antigen challenges in systemically presensitized mouse. The antigen-induced early phase nasal symptoms, nasal hyperresponsiveness to histamine and nasal eosinophilia were significantly suppressed by CTLA4-Ig treatment. Elevation of serum level of antigen-specific IgE, but not IgG1 or IgG2a was inhibited by the treatment. In relation to cytokine levels in the tissue extracts of the nasal mucosa, an up-regulation of IL-4 was significantly inhibited, however, the levels of IL-5 and IFN-gamma were not affected by the treatment. These results suggest that B7/CD28-CTLA4 costimulatory pathway plays an important role in on-going Th2-related allergic reactions in the nose.

Role of CD4-positive T cells in the pathogenesis of nasal allergy in the murine model.

BACKGROUND: Antigen-induced upregulation of cytokines, especially Th2-type cytokines, has been proven to be closely related to allergic inflammation in nasal allergy. CD4-positive T cells are supposed to play an important role not only in the induction of allergy but also in allergic inflammation. METHODS: The anti-CD4 mAb was administered to the murine model of nasal allergy either at the beginning of sensitization, just before antigen challenge or during a topical booster sensitization. Then, the effects on the antigen-induced nasal responses and the serum level of antigen-specific IgE antibody were evaluated. RESULTS: When the mAb was applied at the beginning of sensitization, the early-phase nasal symptoms and the late-phase nasal eosinophilia were significantly inhibited, and the 8-day passive cutaneous anaphylaxis (PCA) titer tended to be inhibited. When the mAb was applied just before the challenge, there were no differences in the nasal symptoms, the nasal eosinophilia or the 8-day PCA titer between the mAb-treated animals and the control animals. When the mAb was applied during a topical booster sensitization, the nasal eosinophilia, the 8-day PCA titer and histamine hypersensitivity were significantly suppressed in the treated animals. CONCLUSION: CD4-positive T cells play an important role in the induction of IgE-mediated nasal allergy, occurrence of late-phase allergic inflammation and histamine hypersensitivity, but not in antigen-induced early-phase nasal symptoms in the murine model. In cases of chronic topical antigen exposure, however, the suppressive effects of a single application of the anti-CD4 mAb are not remarkable.

[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent head and neck cancer].

A late phase II clinical study of RP56976 (docetaxel), a new anticancer agent for advanced/recurrent head and neck cancer, was conducted in 29 institutions all over Japan as a multi-institutional cooperative study. Docetaxel was administered by 1 to 2-hour intravenous infusion at a dose of 60 mg/m2 every 3 to 4 weeks. Of 63 patients eligible in this study, 59 were judged as complete cases. Complete response (CR) was observed in 1 patient, partial response (PR) in 13, no change (NC) in 25, and progressive disease (PD) in 20, for an overall response rate of 22.2% (14/63, 95% CI: 12.7-34.5%) in eligible cases, and 23.7% (14/59, 95% CI: 13.6-36.6%) in complete cases. Previously treated patients showed a 17.9% (10/56) response rate, whereas treatment--naive patients showed a 57.1% (4/7) response rate. Among 46 patients who received prior chemotherapy, one CR and 7 PR were observed with a 17.4% response rate. Major hematological toxicities were leucopenia in 95.1% (> or = grade 3, 59.7%) and neutropenia in 90.3% (> or = grade 3, 79.0%). Other severe toxicities (> or = grade 3) included anorexia in 9.7% (6 cases), diarrhea in 3.2% (2 cases), dyspnea in 3.2% (2 cases), and fatigue in 3.2% (2 cases). One patient had a grade 3 interstitial pneumonia; however, symptoms were resolved by the administration of corticosteroids. During this study, one patient died due to multiple organ failure (MOF) caused by disseminated intravascular coagulation (DIC), and this case was reported as a therapy-related death. Based on these results, docetaxel is an active agent for treatment of head and neck cancer.

Expression of substance P (NK1) receptor mRNA in human nose.

In airway tissues, it has been suggested that substance P is the transmitter of afferent sensory nerves which respond to various irritants and may be involved in airway allergic reactions. Three classes of tachykinin receptor are currently recognized, denoted as NK1, NK2 and NK3, which exhibit preferential affinity for substance P, neurokinin A and neurokinin B, respectively. We used molecular probes to study the gene expression and distribution of NK1 receptor in human nose. Total RNA was isolated from human nasal mucosa and NK1 receptor mRNA was detected in these tissues by using reverse transcription and polymerase chain reaction (RT-PCR). For in situ hybridization study of human nasal mucosa, we utilized the PCR directly to incorporate a T7 RNA polymerase promoter sequence onto the NK1 receptor cDNA, and these PCR products were used as the DNA templates for producing digoxigenin-labelled anti-sense and sense RNA probes. These studies revealed that NK1 receptor mRNA was expressed in submucosal glands and airway epithelium. The results may have an important clinical implication, and also promote further investigation of gene regulation of NK1 receptor in health and disease.

Serum antibodies specific to CD outer membrane protein of Moraxella catarrhalis, P6 outer membrane protein of non-typeable Haemophilus influenzae and capsular polysaccharides of Streptococcus pneumoniae in children with otitis media with effusion.

We measured the levels of serum IgG antibodies to CD outer membrane protein of Moraxella catarrhalis, P6 outer membrane protein of non-typeable Haemophilus influenzae and capsular polysaccharides of Streptococcus pneumoniae in 168 children with otitis media with effusion (OME) who were followed prospectively, using ELISA. Serum IgG antibodies to CD, P6 and pneumococcal capsular polysaccharides were detected in all samples. The anti-pneumococcal polysaccharides antibody level was highest, followed by the anti-P6 antibody level and anti-CD antibody was lowest (median:interquartile ranges were 45.9:19.1-100 microg/ml, 15.6:9.70-23.2 microg/ml and 1.06:0.73-1.87 microg/ml, respectively). In children aged 0-6 years, there were positive correlations among the antibody levels (anti-CD vs anti-P6, r=0.325, p <0.001; anti-CD vs anti-polysaccharide, r=0.397, p <0.0001; anti-P6 vs anti-polysaccharide, r=0.175, p=0.057). However, no relationship was seen in children aged 7-15 years. Children were classified according to severity of OME during the 1-year follow-up. In children aged 0-6 years, the severity of OME correlated inversely with the levels of anti-CD antibody (r=-.23, p=0.012), of anti-P6 antibody (r=-0.292, p=0.0015), and of anti-pneumococcal polysaccharides antibody (r=-0.25, p=0.0064). However, no correlation was found between antibody levels and severity of OME in children aged 7-15 years. These data suggest that persistence and/or recurrence of OME may be due to an insufficient serum antibody response to middle ear pathogens in young children.