A Targeted Genetic Association Study of the Rare Type of Osteomyelitis.

Chronic nonbacterial osteomyelitis is a rare bone disorder that can be found in the jaw. It is often associated with systemic conditions, including autoimmune deficiencies. However, little is known about how the genetic and immunologic background of patients influences the disease. Here, we focus on human leukocyte antigen (HLA), killer cell immunoglobulin-like receptors (KIRs), and their specific combinations that have been difficult to analyze owing to their high diversity. We employed a recently developed technology of simultaneous typing of HLA alleles and KIR haplotype and investigated alleles of the 35 HLA loci and KIR haplotypes composed of centromeric and telomeric motifs in 18 cases and 18 controls for discovery and 472 independent controls for validation. We identified an amino acid substitution of threonine at position 94 of HLA-C in combination with the telomeric KIR genotype of haplotype tA01/tB01 that had significantly higher frequency (>20%) in the case population than in both control populations. Multiple logistic regression analysis based on a dominant model with adjustments for age and sex revealed and validated its statistical significance and high predictive accuracy (C-statistic ≥0.85). Structure-based analysis revealed that the combination of the amino acid change in HLA-C and the telomeric genotype tA01/tB01 could be associated with lower stability of HLA-C. This is the first case-control study of a rare disease that employed the latest sequencing technology enabling simultaneous typing and investigated amino acid polymorphisms at HLA loci in combination with KIR haplotype.

Huge ameloblastic carcinoma of the mandible with metastases treated in several different ways.

Ameloblastic carcinoma is an extremely rare, aggressive, malignant tumour that is most common in the mandible. Because of its rarity there is no general approach to treatment. We present a rare case of an ameloblastic carcinoma with multiple metastases in a 63-year-old Japanese man that was treated in several different ways, including chemoradiotherapy and immunotherapy.

Usefulness of intra-oral ultrasonography to predict neck metastasis in patients with tongue carcinoma.

OBJECTIVE: To assess tissue characterization relating with neck metastasis of invasive tongue cancer, we investigate the usefulness of intra-oral ultrasonography (US). MATERIALS AND METHODS: The patients with squamous cell carcinoma of the tongue (n = 110) were preoperatively evaluated with intra-oral US. The US images were compared with histological sections. The histological and ultrasonographic parameters were evaluated for their correlation with neck metastasis. RESULTS AND CONCLUSION: High-quality ultrasonic images were obtained, and all lesions over 1 mm thickness by histology were detected. There was a significant correlation (P < 0.0001) between measurements of tumor thickness by US and histology. Univariate analysis showed that the histological parameters influencing neck metastasis were mode of invasion (P = 0.0006), muscular invasion (P < 0.0001), stromal reaction (P = 0.0002), and tumor thickness (P = 0.0004). Of the ultrasonographic parameters, shape of margin (P = 0.019), pattern of margin (P = 0.033), internal echo signal (P = 0.035), and tumor thickness (P < 0.0001) showed a significant correlation with neck metastasis. Ultrasound images of oral tongue cancer reflected the histological structures. Tumors with diffuse invasive mode shows an irregular and unclear tumor margins on US image. Thickness of 8 mm by ultrasound is useful as a cut-off point of predicting risk of neck metastasis of tongue cancer. Intra-oral US is a reliable tool in objectively predicting subclinical neck metastasis in tongue cancer.

Lateral cephalometric analysis of the pharyngeal airway space affected by head posture.

To clarify the relationship between head posture and pharyngeal airway space (PAS), the cephalometric parameters at different head postures were examined. Twelve normal Japanese adults (6 males and 6 females) were examined. Lateral cephalometric radiographs were taken at five different head postures in each person. All radiographs were traced, and the measurements were analyzed statistically. PAS was significantly increased by forward inclination of the cervical spine. The most significant correlation was found between the change in CVT/NSL (cranio-cervical inclination in the second and fourth vertebrae) and the change in PAS-TP (the minimal pharyngeal airway space) (r(2)=0.79 in males, r(2)=0.67 in females). The mean CVT/NSL when the head was in the natural (neutral) position was 100.9 degrees in males and 103.5 degrees in females. Linear regression analysis revealed DeltaPAS (mm)=0.37DeltaCVT/NSL (degree) (r(2)=0.79, p<0.0001) in males, and DeltaPAS (mm)=0.33DeltaCVT/NSL (degree) (r(2)=0.51, p<0.0001) in females. The correlation equations were obtained as follows: the corrected PAS (mm)=the actual PAS (mm)+0.37[100.9-the actual NSL/CVT (degree)] in males, and the corrected PAS (mm)=the actual PAS (mm)+0.33[103.5-the actual NSL/CVT (degree)] in females. These results will contribute to obtaining an accurate assessment of the PAS that should be corrected by the cranio-cervical inclination.

Intraoral vertico-sagittal ramus osteotomy: modification of the L-shaped osteotomy.

The sagittal split ramus osteotomy and intraoral vertical ramus osteotomy carry the potential risk of postoperative nerve paralysis, bleeding, and fracture and dislocation of the condyle. In 1992, Choung first described the intraoral vertico-sagittal ramus osteotomy for the purpose of avoiding postoperative dislocation of the condyle. However, there is still potential for damaging the inferior alveolar nerve and maxillary artery with this technique. The authors have developed a modified technique to minimize these risks. An evaluation of surgical experience and patient outcomes with the use of this technique is presented herein. One hundred twenty-two sides in 97 Japanese patients diagnosed with a jaw deformity were analyzed. This technique includes a horizontal osteotomy that is performed at a higher position than in the original Choung procedure. Intraoperatively, there was no unexpected bleeding from the operative site. Proximal segment dislocation from the glenoid fossa was observed on one side (0.82%). Non-union of the osteotomy was not observed in any patient. Intraoperative fracture of the coronoid process occurred in 2.46%, but none necessitated treatment of the fracture. Nerve dysfunction was found in 2.46% at the 12-month postoperative follow-up. The modified technique presented herein was developed to reduce postoperative nerve dysfunction and intraoperative hemorrhage.

Intratumoural expression of thymidylate synthase is an independent predictor of prognosis in patients with squamous cell carcinoma of the tongue: results from a retrospective study.

The aim of this study was to assess the importance of immunohistochemical thymidylate synthase (TS) expression level as a prognostic marker in tongue cancer patients. In 140 patients with primary squamous cell carcinoma (SCC) of the tongue, intratumoural TS expression was evaluated by immunohistochemistry. The level of TS expression was determined by a semiquantitative scoring system, ranging from 1+ to 3+ according to the ratio of TS-positive cells. Of 140 patients, 64 (45.7%), 49 (35.0%) and 27 (19.3%) were assessed as 1+, 2+ and 3+, respectively. Univariate analyses demonstrated that both disease-free survival (DFS) and overall survival (OS) were significantly lower in patients with a TS 3+ tumour than in those with a TS 1+/2+ tumour (DFS: P = 0.0082, OS: P = 0.0100). In a multivariate analysis using the Cox regression model, cervical lymph-node status and TS expression level were selected as independent factors for DFS and OS. Maintenance adjuvant chemotherapy by oral 5-fluorouracil (5-FU) significantly improved DFS and OS in patients with a TS 1+/2+ tumour (DFS: P = 0.0027, OS: P = 0.0398). These data suggest that the level of immunohistochemical TS expression is an independent prognosticator in patients with tongue SCC, and may be useful in the selection of patients who would benefit from oral 5-FU adjuvant chemotherapy.

Excitatory GABAergic synaptic potentials in the mesencephalic trigeminal nucleus of adult rat in vitro.

The mesencephalic trigeminal nucleus (MesV) contains the somata of primary afferent neurons innervating masticatory muscle spindles and the periodontal membrane. MesV afferent somata are unique in receiving synaptic inputs. Intracellular recordings in coronal pontine slices from adult rats were made from MesV neurons identified by having Cs-sensitive inward rectification and pseudounipolar morphology. Stimuli near the MesV evoked either a cluster of action potentials superimposed on a postsynaptic potential (PSP) or an antidromic spike at resting membrane potential (RMP). Membrane hyperpolarization revealed that each cluster of action potentials consisted of an antidromic spike and a subsequent PSP. Evoked PSPs in slices and miniature postsynaptic currents (mPSCs) recorded using whole-cell patch in dissociated MesV neurons were resistant to glutamate antagonists and strychnine but were reversibly abolished by 40 microM bicuculline. Superfusion of 1-10 mM GABA decreased input resistance and depolarized the membrane. Reversal potentials for evoked PSPs and GABA-induced depolarizations were similar and close to that for mPSCs which matched the Cl- equilibrium potential. Thus activation of synapses on MesV somata evokes GABAergic PSPs that generate action potentials at RMP in the adult. These data also indicate that primary afferent MesV neurons can act as interneurons in the central control of mastication.

Expression of matrix metalloproteinase-2 related to lymph node metastasis of oral squamous cell carcinoma. A clinicopathologic study.

To investigate the effect of matrix-degrading enzymes on the malignant potential of oral squamous cell carcinoma, the expression of matrix metalloproteinase-2 (MMP-2/72-kD gelatinase/type IV collagenase) in 46 patients who had neck surgery for oral cancer was studied immunohistochemically. In 20 of 26 patients (76.9%) with lymph node metastases, proMMP-2 was strongly expressed, whereas the production of proMMP-2 in tissue was detected only in 5 of 20 patients (25%) who had no lymph node metastases. In tissue specimens, proMMP-2 was expressed in a diffuse invasive mode and in the advancing front of cancer. Because MMP-2 can degrade type IV collagen composed of basement membrane, these results suggest that the in vivo production of the enzyme by cancer is an indicator of the degree of malignancy, and that the analysis of proMMP-2 expression is useful to evaluate the malignant potential in individual oral squamous cell carcinoma.

Myocardial contusion caused by a baseball.

Myocardial contusion is a rare type of sports injury. We report a case of myocardial contusion caused by a baseball. In this patient, arrhythmias were induced by an exercise test 1 week after injury. That patients with myocardial contusion but without arrhythmias at rest need to be treated carefully is emphasized.

Congenital teratoid cyst of the floor of the mouth--a case report.

A case of sublingual congenital teratoid cyst is reported and the recent literature is reviewed. Histopathologic study of the enucleated cyst revealed striated muscle, cartilage, fat, salivary gland tissue, and gastrointestinal epithelium in a cyst wall of dense fibrous tissue with a thin layer of ciliated columnar and partially stratified squamous epithelium.

Scrape cytology of oral pemphigus. Report of a case with immunocytochemistry and light, scanning electron and transmission electron microscopy.

BACKGROUND: Pemphigus vulgaris is a disseminated disease of the skin and mucous membranes characterized by recurrent vesicular and bullous lesions due to the autoantigen belonging to the cadherin type of cell adhesion molecules. The presence of acantholysis associated with immunoglobulins in the intercellular spaces and on the cell membrane are diagnostic features. However, the appearance of smears from the oral cavity by scanning (SEM) and transmission electron microscopic (TEM) study as well as immunocytochemistry of cadherin does not appear to have been previously reported. CASE: A 67-year-old female developed erosion on her gingiva with severe pain. On oral examination, there were ulcerations on the palate, and the Nikolsky sign was positive. The characteristic cytologic findings from oral scrapes were high cellularity, a bloody background and a predominant cell population consisting of polygonal basal and parabasal cells with pronounced nucleoli. Also present were degenerative cell changes: e.g., cytoplasmic vacuoles and a homogeneous nuclear appearance. Immunocytochemical staining for IgG and cadherin gave a positive reaction in the intercellular spaces and on the cell membranes. The surface of cells in pemphigus vulgaris by SEM showed somewhat irregularly distributed microridges, and TEM revealed desmosomal attachments, degenerated tonofilaments with pronounced nucleoli and heterochromatin. As a result of cytodiagnosis, additional appropriate specimens were obtained at the time of the scraping for confirmatory immunocytochemistry for cadherin, SEM and TEM studies. CONCLUSION: The results demonstrate that a precise diagnosis of pemphigus vulgaris can be rendered on cellular material and cadherin immunocytochemistry obtained by scrape from the oral mucosa.

A hamartoma-like mass on the palate? A possible discussion regarding the components of a pigmented naevus and hyperplastic salivary gland.

An extremely rare mass lesion arising on the hard palate is presented. The patient was a 49-year-old Japanese male. He had a painless, semi-globular, smooth-surfaced and partially pigmented mass located on the left hard palate with no evidence of growth for approximately 20 years. The resected specimen included hyperplastic salivary gland tissue, nerve fibres and vessels surrounded by adipose tissue. All constituent tissues showed excessive growth for this location. Also spiralling nests of naevus cells representing inactive intramucosal naevus were included. We consider the whole lesion to be a hamartoma.

Epithelial-myoepithelial carcinoma--report of a case arising in the nasal cavity.

We present an extremely rare case of epithelial-myoepithelial carcinoma (EMC) arising in the nasal cavity. The patient was a 56-year-old Japanese male with a polypoid tumour arising from the nasal septum. Histopathological examination revealed the tumour to consist of a solid proliferation of clear-cells and, in some areas, small or elongated duct structures with a double-layered arrangement of inner cuboidal cells and outer clear-cells. Dual differentiation toward myoepithelial and ductal cells were confirmed immunohistochemically. The occurrence of EMC in the nasal cavity is possible and this entity should be generally recognized by surgical pathologists, not only those engaged in head and neck surgery.

Clinicopathologic parameters in predicting cervical nodal metastasis in early squamous cell carcinoma of the oral cavity.

A retrospective study of ninety patients with early squamous cell carcinoma of the oral cavity was undertaken to evaluate clinical and histopathologic parameters in predicting cervical lymph node metastasis. Medical records were examined for age, sex, primary site, growth pattern, and size. The specimens from biopsy and surgical excision were examined for the degree of differentiation, mode of invasion, tumor thickness, muscular invasion, vascular invasion, and inflammatory response. The mode of invasion and tumor thickness were important indicators in the prediction of cervical lymph node metastasis. Tumors with Grade 4 mode of invasion exceeding 3 mm in thickness or with Grade 3 and 4 modes of invasion and more than 6 mm in thickness had a high incidence of cervical nodal metastasis. These important prognostic variables were best evaluated in the deeper portions of the lesions.

Two cases of recurrent herpetic infection of the tongue.

Recently, a number of reports have been published on recurrent herpetic infection of the oral mucosa. In most of these cases, the infected tissue is the fixed intraoral mucosa, such as the gingiva or hard palate. Infection of movable mucosa such as the tongue, which is reported in the present paper, has not been reported in detail previously. In each of the two cases reported in the present paper, intraoral lesions were diagnosed as recurrent herpes-glossitis after isolation of the herpes simplex virus (HSV).

Recurrent herpetic infection of the oral floor--a case report.

Recurrent herpetic infection on the mobile mucosa such as the oral floor, has not been reported previously. A case of recurrent herpetic infection of the oral floor in a 52-year-old man is presented. This case illustrates the fact that recurrent herpetic lesions can occur anywhere in the intra-oral mucosa.

Comparison of the inpatients admitted during the recent 5 years (January 1994-December 1998) with those admitted during the previous 5 years (January 1989-December 1993): a clinico-statistical study.

As society ages, the composition of the diseases that occur within it changes accordingly. With that in mind, we examined the characteristics and trends in the recent inpatients and compared these recent inpatients with those of a previous report to identify the changes that accompany the aging of society. Subjects were 1,534 cases (men 56.9%, female 43.1%, average age 47.1 years) who were hospitalized at Kurume University Hospital for treatment during the 5-year period from January 1st, 1994 through December 31st, 1998. The ratio of inpatients over 65 years old was about 1.8 times higher than in the previous study, showing a clear trend toward an increased overall age of inpatients. As for the types of disease observed, the most common malignancies were epithelial tumor, followed by other benign tumors, as well as 76 cases which included diseases resembling tumor (epulis and exostosis etc.). A majority of the patients (55.6%) were directed to the Hospital by their dentist, a finding similar to that of the previous report. As for geographical distribution, 93.3% of the inpatients lived within 40 km of the center of Kurume City where our oral surgery is located, an increase of about 10% from the last report. In other words, our results showed a reduction in the sphere of treatment distribution.

Congenital epulis--an electron microscopic observations of two cases.

Two cases of congenital epulis occurring in the gingiva at the site where the lower deciduous incisors were to erupt are described. The first patient was a 7 day-old female infant. Her epulis was diagnosed, histopathologically, as a granular cell tumor. Electron microscopy revealed that the tumor cells were large with small eccentric nuclei. The cells were filled with granular structures. These granular substances varied in size and electron density. Case 2 involved a 37 day-old male infant. A histopathological diagnosis of fibromatosis was made. Electron micrographs showed a proliferation of cells which resembled fibroblasts. These cells varied in shape, including some with thin, long processes. Abundant reticular and collagen fibers were present in the stroma. In both cases, the postoperative course was uneventful without recurrence.

Expression of matrix metalloproteinase-3 in stage I and II squamous cell carcinoma of the oral cavity.

PURPOSE: The object of this study was to evaluate the significance of matrix metalloproteinase-3 (MMP-3) in tumor invasion and metastasis of early squamous cell carcinoma (SCC) of the oral cavity. MATERIALS AND METHODS: Surgical specimens from 65 patients with stage I and II SCC of the oral cavity were the subjects of this study. Tissue specimens were fixed in formalin and embedded in paraffin, and the sections were stained with monospecific antibodies against human MMP-3 by the avidin-biotin-peroxidase complex method. RESULTS: Of the 65 patients, 30 (46.2%) tested positive for MMP-3. Immunoreactivity revealed the expression of MMP-3 to be in the small cancer nests in the advancing front of invasion, but not in normal oral epithelium. MMP-3 expression was positively correlated with tumor size, depth of tumor invasion, diffuse invasive mode, and the high incidence of lymph node metastasis. CONCLUSION: MMP-3-containing tumors will invade adjacent normal tissues more aggressively, including lymphatic and blood vessels. Therefore, the examination of MMP-3 expression in biopsy specimens should provide information useful in predicting the malignant potential of early SCC of the oral cavity.