Involvement of Microglial P2Y12 Signaling in Tongue Cancer Pain.

To elucidate if microglial P2Y12 receptor (P2Y12R) mechanisms are involved in the trigeminal spinal subnucleus caudalis (Vc; also known as the medullary dorsal horn) in intraoral cancer pain, we developed a rat model of tongue cancer pain. Squamous cell carcinoma (SCC) cells were inoculated into the tongue of rats; sham control rats received the vehicle instead. Nociceptive behavior was measured as the head-withdrawal reflex threshold (HWRT) to mechanical or heat stimulation applied to the tongue under light anesthesia. On day 14 after the SCC inoculation, activated microglia and P2Y12R expression were examined immunohistochemically in the Vc. The HWRT was also studied in SCC-inoculated rats with successive intra-cisterna magna (i.c.m.) administration of specific P2Y12R antagonist (MRS2395) or intraperitoneal administration of minocycline, a microglial activation inhibitor. Tongue cancer was histologically verified in SCC-inoculated rats, within which the HWRT to mechanical stimulation of the tongue was significantly decreased, as compared with that of vehicle-inoculated rats, although the HWRT to heat stimulation was not. Microglia was strongly activated on day 14, and the administration of MRS2395 or minocycline reversed associated nocifensive behavior and microglial activation in SCC-inoculated rats for 14 d. The activity of Vc wide dynamic range nociceptive neurons was also recorded electrophysiologically in SCC-inoculated and sham rats. Background activity and noxious mechanically evoked responses of wide dynamic range neurons were significantly increased in SCC-inoculated rats versus sham rats, and background activity and mechanically evoked responses were significantly suppressed following i.c.m. administration of MRS2395 in SCC-inoculated rats as compared with sham. The present findings suggest that SCC inoculation that produces tongue cancer results in strong activation of microglia via P2Y12 signaling in the Vc, in association with increased excitability of Vc nociceptive neurons, reflecting central sensitization and resulting in tongue mechanical allodynia.

Local application of Aqua Titan improves symptoms of temporomandibular joint muscle disorder: a preliminary study.

Aqua Titan (AT), comprising microscopic titanium particles dispersed in water, has been reported to have beneficial effects on muscle tissue. This study investigated the effects of local application of AT on symptoms in patients with muscle disorders of the temporomandibular joint (TMJ) compared to patients with joint disorders of the TMJ. Sixteen patients with unilateral masseter muscle pain during motion (muscle disorder group) and six patients with unilateral TMJ pain during motion (joint disorder group) applied an AT-permeated patch over the painful area every night for 2 weeks. Symptoms were evaluated clinically at the initial visit and 1 and 2 weeks later. Clinical symptoms in the joint disorder group showed no tendency towards improvement after 2 weeks. In contrast, mouth opening range with/without pain, visual analogue scale (VAS) scores for pain during mouth opening and eating, and activities of daily living (ADL) scores in the muscle disorder group were improved significantly after 2 weeks. Multiple comparison tests in the muscle disorder group showed significant improvements in the VAS for eating and ADL score after 1 week. These results suggest that the AT patch has a potential supplementary role in the treatment of patients with muscle disorders of the TMJ.

Long-term evaluation of swallowing function before and after sagittal split ramus osteotomy.

The aim of this study was to determine whether mandibular setback by sagittal split ramus osteotomy (SSRO) influences swallowing function. The subjects were 14 patients with skeletal class III malocclusions who underwent setback surgery by SSRO. Morphological changes were studied on cephalograms, and swallowing function was evaluated by videofluorography before the operation (T0) and at 7-10 days (T1), 3 months (T2), and 6 months (T3) after surgery. The angle between nasion, sella, and hyoid bone (HSN) and the sella-hyoid distance had increased significantly at T1. The hyoid bone returned to the preoperative position at T2. There were no significant changes in the oropharyngeal space at any time. On videofluorographic assessment, lingual movement, soft palate movement, and epiglottic movement had decreased at T1, but all patients recovered at T2. The oral transit time was significantly longer at T1 than at T0. Our results confirm that SSRO influences swallowing function. Swallowing function appears to stabilize by 3 months after surgery.

A novel method for designing and fabricating custom-made artificial bones.

Artificial bones are useful for tissue augmentation in patients with facial deformities or defects. Custom-made artificial bones, produced by mirroring the bone structure on the healthy side using computer-aided design, have been used. This method is simple, but has limited ability to recreate detailed structures. The authors have invented a new method for designing artificial bones, better customized for the needs of individual patients. Based on CT data, three-dimensional (3D) simulation models were prepared using an inkjet printer using plaster. The operators applied a special radiopaque paraffin wax to the models to create target structures. The wax contained a contrast medium to render it radiopaque. The concentration was adjusted to achieve easy manipulation and consistently good-quality images. After the radiopaque wax was applied, the 3D simulation models were reexamined by CT, and data on the target structures were obtained. Artificial bones were fabricated by the inkjet printer based on these data. Although this new technique for designing artificial bones is slightly more complex than the conventional methods, and the status of soft tissue should also be considered for an optimal aesthetic outcome, the results suggest that this method better meets the requirements of individual patients.

Establishment of temporomandibular joint puncture technique in rats using in vivo micro-computed tomography (R_mCT®).

The aim of the report was to establish puncture techniques for the temporomandibular joint (TMJ) cavity in rats. The experimental sample comprised 30 male Sprague-Dawley rats. Under general anaesthesia the superior joint cavity of the rat was punctured either laterally (lateral puncture technique (LPT), n = 11), anteriorly (anterosuperior puncture technique (ASPT), n = 13) or anteroinferior puncture technique (AIPT), n = 6) using a 27-gauge needle. After the tip of the needle was confirmed by micro-CT (R-mCT®, Rigaku, Tokyo, Japan) located on the mandibular fossa, 0.05 ml of contrast media was injected under micro-CT fluoroscopic guidance. After confirmation that the joint cavity was filled with contrast media, micro-CT imaging was carried out. The puncture for LPT was accurate in 5 of the 11 animals. The ASPT was accurate in all 13 animals. The AIPT punctured 3 of the 6 animals. Furthermore, the ASPT and AIPT demonstrated improved preservation of the needle; it was harder to detach the needle, which led to greater stability. These results suggest that ASPT assisted by R-mCT® is useful for basic research, including drug discovery and pathogenesis of TMJ diseases.

Use of a replica graft tooth for evaluation before autotransplantation of a tooth. A CAD/CAM model produced using dental-cone-beam computed tomography.

A 33-year-old man was referred by a local dentist for autotransplantation of the right mandibular third molar to the site of the left mandibular first molar. Before the operation, dental-cone-beam computed tomography was performed to measure the dimensions of the graft tooth and the bone volume of the socket. The three-dimensional (3D) structure of the graft tooth was created from the 3D imaging data. A replica of the graft tooth was produced using a stereolithographic CAD/CAM system before autotransplantation. A socket of the appropriate size and structure was created and the graft tooth was extracted immediately before grafting. This procedure shortened the time needed to fit the graft tooth into the socket and reduced injury to the periodontal membrane. The postoperative outcomes of autotransplantation of the tooth were good.

A case of tumoural calcinosis in the temporomandibular joint associated with systemic sclerosis.

Systemic sclerosis (SSc) is a relatively rare condition characterized by the excessive production and deposition of collagen within tissue. This condition is thought to be immunologically mediated and, in addition to its notorious cutaneous manifestations, often involves multiple organs. A case is presented of systemic sclerosis associated with extensive tumoural calcinosis in the temporomandibular joint. There has been no evidence of recurrence or complications during approximately 2 years of follow up, but long-term follow up is essential.

Cyclooxygenase-2 activity is essential for the osseointegration of dental implants.

The aim of this study was to examine the effect of cyclooxygenase (COX)-2 on bone response after the placement of implants in the femurs of mice. titanium implants 1.0mm in diameter were placed into the middle of the femurs of 9-week-old male COX-2 wild-type (COX-2(+/+)) and knockout (COX-2(-/-)) mice. For RNA analysis, the mice were killed 0, 1, 2, 4, 7 and 56 days after implantation. RNA was extracted from the bone surrounding the implants. For histological analysis, the mice were killed 4 and 8 weeks after treatment, and undecalcified sections were prepared. Contact microradiography was performed, and the sections were stained with 1% toluidine blue for histological examination. Histomorphometric measurements were obtained with a computer-based image analyser to quantify bone newly formed around the implant and the rate of implant-bone contact. Expression of COX-2 and osteocalcin mRNA was induced in bone surrounding implants in COX-2(+/+) mice, but not in COX-2(-/-) mice. In cortical bone, the implant surface was in direct contact with newly formed bone lamellae in COX-2(+/+) mice; new bone formation was minimal in COX-2(-/-) mice. These results suggest that COX-2 plays an essential role in osseointegration and provide evidence that COX-2-selective non-steroidal anti-inflammatory drugs may interfere with osseointegration clinically.

A 2-stage procedure combining maxillary advancement by distraction technique with mandibular setback surgery in patients with cleft lip and palate.

A 2-stage procedure combining maxillary advancement by distraction technique with mandibular setback surgery was used to correct jaw deformities in 5 patients with severe maxillary retrusion secondary to cleft lip and palate. First, a Le Fort I maxillary osteotomy was performed. Immediately after maxillary distraction, the distraction device was removed. The advanced maxilla was fixed with miniplates after adjusting the length and direction of advancement, and mandibular setback surgery was performed simultaneously to obtain a normal occlusal relationship. This 2-stage procedure resulted in stable occlusion and a markedly improved facial profile.

Correction of cleft lip nasal deformity in Orientals with a cantilevered iliac bone graft.

We describe our technique for correcting a nasal deformity associated with cleft lip in oriental people. Cantilevered iliac bone grafts are used to provide additional structural support and to achieve the desired nasal projection and profile. Augmentation of the nasal bridge creates the illusion of a narrower nose. This technique was used in 20 patients with severe nasal deformities. Clinically and radiographically it consistently produced good, long-lasting results.

Large myxofibroma of the mandible treated with segmental mandibular resection and vascularized fibular graft.

This report summarizes a case of large myxofibroma of the mandible. On the basis of the clinical appearance, radiographic findings, and biopsy specimen, the lesion was diagnosed as a myxofibroma. Segmental mandibular resection and immediate reconstruction by vascularized fibular graft were performed. At the 18-month follow-up there was no evidence of recurrence of the tumor, and good functional and aesthetic results were maintained.

Intramuscular haemangioma of the anterior chest wall.

Intramuscular haemangiomas of the chest wall are rare. We present the case of a 33-year-old man with an intramuscular haemangioma of the left side of the anterior chest wall located in the left sixth intercostal space. We resected the tumour and surrounding tissue. Histopathological examination of the tumour demonstrated an intramuscular haemangioma of small-vessel type. The patient has been free of recurrence for 5 years after surgery.

[Recent advance in head and neck reconstruction].

The clinical application of microvascular free-flap transfers in reconstructive surgery has expanded tremendously since their introduction. Difficult reconstruction in the head and neck region can now be accomplished in a one-stage procedure using these techniques. Free flaps such as rectus abdominis, forearm, and scapular flap have been used frequently in this region because of their many advantages. They have a long vascular pedicle of a large-caliber vessel with anatomic stability and have ample blood supply. It is easy to harvest, and donor site morbidity in negligible. However, further improvement and refinement of surgical procedures are required to obtain better functional results and increase patients' quality of life. In this article, we describe the most recent concepts and techniques in head and neck reconstruction.

Distraction of scarred soft tissue before secondary bone grafting. A case report.

Mandibular distraction was performed to restore oral function in a 52-year-old man with tongue cancer, in whom a mandibular fracture developed after marginal resection of the mandible. The fracture caused the mandibular dental arch to be shorter than the maxillary arch. An external fixation device was attached to the collapsed mandible. The mandibular soft tissue was expanded by 32 mm. After gradual distraction, a vascularized iliac bone graft was transferred to the lengthened space. Subsequently, vestibuloplasty was performed and implants were inserted. A normal appearance, acceptable occlusion and satisfactory oral function were achieved.

Significant association of HLA-B and HLA-DRB1 alleles with cleft lip with or without cleft palate.

Nucleotide sequence level typing of HLA-B, -DRB1, and -DPB1 alleles was performed on Japanese patients with cleft lip with or without cleft palate (CL/P). Two HLA-B alleles, B*1501 and B*5101, showed a significant positive association with CL/P. The increase of B*1501 was evident in female patients (OR=3.6, Pc=0.003), whereas the increase of B*5101 was evident in male patients (OR=3.7, Pc < 0.001). One HLA-DRB1 allele, HLA-DRB1*0802 also showed an increase in CL/P patients. Conversely, HLA-B*4403 and DRB1*1302 were not observed in the patient group (Pc=0.01 and Pc=0.02, respectively). No HLA-DPB1 alleles showed significant association with CL/P. Thus, the present study indicates that HLA alleles, or closely linked loci, may be involved in the pathogenesis of CL/P.

Secondary lengthening of the reconstructed mandible using a gradual distraction technique--two case reports.

We have performed mandibular lengthening to restore oral function in 2 cases after tumour resection. Both cases had already undergone a vascularised fibular graft for mandibular reconstruction and had severe contracture and absence of an alveolar ridge for dentures. Gradual distraction was applied after corticotomy of the fibular bone at 0.9 mm per day. After completion of bone lengthening of 20-30 mm, both patients underwent a split thickness skin graft to obtain a good alveolar ridge for dentures and implants. Osteointegrated implants have since been applied in one of these cases, and the other patient has been able to eat a normal diet using dentures. Gradual distraction is applicable for vascularised bone grafts and useful for restoration of the alveolar ridge to accommodate dentures in cases with severe contracture of the oral space after tumour ablation.

Immediate free flap reconstruction for head and neck pediatric malignancies.

We performed six immediate free flap reconstructions after tumor ablation in 5 children under the age of 15 years presenting with head and neck malignancy. One patient underwent free flap transfer on two separate occasions because of tumor recurrence. There were no flap losses nor were there any complications related to microvascular surgery. Although a pediatric head and neck malignant tumor is rare, surgical resection is the primary therapeutic role for those that are amenable to complete excision. Pediatric microsurgery provides a safe and reliable procedure for reconstruction of head and neck defects after extirpation of the tumor.

A unilateral cleft lip patient with holoprosencephaly.

Holoprosencephaly includes a spectrum of conditions that have in common the associated anomalies of false median cleft lip, nasal malformation, orbital hypotelorism, and brain malformations. We recently encountered a patient with holoprosencephaly presenting with a rare unilateral cleft of the lip. This patient was potentially viable, although mental development was retarded.

Modification of the Abbé flap for reconstruction of the vermilion tubercle and Cupid's bow in cleft lip patients.

PURPOSE: This article reports on the modification of the Abbé flap for correction of mild tightness of the corrected cleft lip deformity. PATIENTS AND METHODS: Twelve patients with a moderately tight lip deformity, from 16 to 35 years old, underwent this procedure. Nine had a unilateral deformity and 3 a bilateral deformity. The flap, which was taken from the central portion of the lower lip vermilion, was designed to repair the vermilion tubercle and the Cupid's bow. A tiny portion of skin was included to facilitate closure of the donor site. It was inserted into the center of the upper lip and the pedicle was divided 1 week after operation. RESULTS: Each patient showed a more natural contour of the vermilion tubercle and the Cupid's bow. The scarring of the donor site was inconspicuous. CONCLUSIONS: Use of modified Abbé flap to reconstruct the contour of the vermilion tubercle and the Cupid's bow makes the upper lip look more natural.