Mandibular distraction osteogenesis in a skeletal Class II patient with obstructive sleep apnea.

We report the orthodontic treatment of a 31-year-old man with severe skeletal Class II malocclusion and documented obstructive sleep apnea (OSA). He had a retrognathic profile with an overbite of 4 mm and an overjet of 14 mm. Mandibular distraction osteogenesis was performed to lengthen the small, retruded mandible by 18 mm and improve the symptoms of OSA. Orthodontic treatment after the mandibular distraction osteogenesis procedure lasted 3 years 1 month. An acceptable occlusion was obtained, and the patient's OSA was significantly alleviated. Although the patient was satisfied with the treatment, condylar resorption was observed. The relevance of condylar resorption with reference to a comprehensive evaluation of the treatment outcome is discussed.

Orthodontic treatment of a patient with Stickler syndrome.

Stickler syndrome (MIM 108300, 604841, 184840) is an autosomal dominant disease characterized by midfacial flattening and variable disorders of vision, hearing and articulation. There are three types of the syndrome caused by mutations in different genes (type 1, COL2A1; type 2, COL11A1; and type 3, COL11A2). About 20% of type 1 patients have cleft palate or bifid uvula, but there have been no case reports of orthodontic treatment of this syndrome so far. The Japanese female patient presented here with Stickler syndrome was characterized by a flat midface and had high myopia, sensorineural hearing loss, enlarged joints, and cleft of the soft palate. She had fairly small SNA and SNB angles and a steep mandibular plane with an enlarged gonial angle. The incisors of both arches were retroclined, and a large overjet and overbite were noted. Orthodontic treatment was initiated at 11 years of age using a lingual arch appliance followed by an edgewise multibracket appliance. Stable functional occlusion was obtained after the treatment. Most of the other seven Stickler syndrome patients exhibited pretreatment characteristics of small SNA and SNB angles, steep mandibular planes, enlarged gonial angles, and retroclined incisors of both arches, demonstrating the characteristic skeletal and occlusal features of this syndrome.

Effects of mandibular advancement on brain activation during inspiratory loading in healthy subjects: a functional magnetic resonance imaging study.

Oral appliances have been a popular treatment option for subjects with obstructive sleep apnea. However, little information is available on how brain activation induced by respiratory challenge is modulated by mandibular advancement with these appliances. We hypothesized that the brain activation caused by respiratory stress may be alleviated by mandibular advancement. Respiratory stress was induced in 12 healthy subjects by resistive inspiratory loading. The effects of mandibular advancement during resistive inspiratory loading were assessed subjectively by using a visual analog scale. These effects were also evaluated objectively by using blood oxygenation level-dependent functional magnetic resonance imaging. The score for the visual analog scale significantly decreased with mandibular advancement. Cortical deactivation, in association with mandibular advancement, was localized to several specific regions, including the left cingulate gyrus and the bilateral prefrontal cortexes. These regions are known to be involved in respiratory control. Our results suggest that mandibular advancement with an oral appliance appears to be useful for reducing respiratory stress, based on both subjective and neuronal criteria.

Orthodontic treatment in a patient with Van der Woude's syndrome.

Van der Woude's syndrome (VDW; #OMIM 119300) is an autosomal dominant disease characterized by cleft lip and/or palate and lower lip pit (fistula). The precise skeletal characteristics are unclear, and there have been no case reports of orthodontic treatment of patients with VDW. The Japanese girl whose treatment is reported here had VDW, including bilateral cleft lip and palate and bilateral symmetric lower lip pits. Orthodontic treatment started when she was just 3 years old, with a removable maxillary expansion appliance, followed by an edgewise multibracket appliance in both arches. Retention began at 11 years of age, and a secondary bone graft was performed for the alveolar cleft. She received prosthetic treatment and achieved a desirable occlusion at 18 years of age. Early intervention helped achieve a satisfactory treatment result for our patient. In contrast, her mother also had VDW, with a severe Class III skeletal pattern, but she had not been treated orthodontically; she had an anterior and lateral crossbite even after prosthetic treatment. The pretreatment characteristics of 4 other subjects with VDW are discussed; they show wide variations in the sizes of the maxilla and the mandible, suggesting that a common skeletal pattern is not generally seen in VDW.

Skeletal characteristics and treatment outcome of five patients with Robin sequence.

OBJECTIVE: To examine the variation in the precise skeletal characteristics and the treatment outcomes of five Japanese Robin sequence cases. MATERIALS AND METHODS: The birth histories and orthodontic records of five Japanese Robin sequence patients were collected and analyzed. RESULTS: All cases had a retrognathic appearance with small SNA and SNB angles. They had significantly steep mandibular planes with lingual tipped incisors in both arches. The gonial angles in two cases were within the Japanese norm, whereas the remaining three showed significantly enlarged angles. Moreover, all cases showed a significantly shorter ramus length, but the mandibular body was short in only two cases. All had moderate or severe crowding in both arches, and therefore extraction of lateral dentition or lateral incisors was performed in conjunction with orthodontic treatment. An edgewise multibracket appliance was placed, and labial tipping of the lower incisors was performed in all cases. All obtained normal functional occlusion after active treatment, but the retrognathic appearance remained in most cases. CONCLUSIONS: The present cases with Robin sequence showed variation in the gonial angle and mandibular body length, although all commonly exhibited smaller SNA and SNB angles with significantly steep mandibular planes. Significant labial tipping of the lower incisors was required during the active treatment, and all cases finally obtained functional occlusion, indicating the relatively good prognosis on the occlusion of this sequence.

Simultaneous maxillary distraction osteogenesis using a twin-track distraction device combined with alveolar bone grafting in cleft patients: preliminary report of a technique.

The simultaneous use of cleft reduction and maxillary advancement by distraction osteogenesis has not been applied routinely because of the difficulty in three-dimensional control and stabilization of the transported segments. This report describes a new approach of simultaneous bilateral alveolar cleft reduction and maxillary advancement by distraction osteogenesis combined with autogenous bone grafting. A custom-made Twin-Track device was used to allow bilateral alveolar cleft closure combined with simultaneous maxillary advancement, using distraction osteogenesis and a rigid external distraction system in a bilateral cleft lip and palate patient. After a maxillary Le Fort I osteotomy, autogenous iliac bone graft was placed in the cleft spaces before suturing. A latency period of six days was observed before activation. The rate of activation was one mm/d for the maxillary advancement and 0.5 mm/d for the segmental transport. Accordingly, the concave facial appearance was improved with acceptable occlusion, and complete bilateral cleft closure was attained. No adjustments were necessary to the vector of the transported segments during the activation and no complications were observed. The proposed Twin-Track device, based on the concept of track-guided bone transport, permitted three-dimensional control over the distraction processes allowing simultaneous cleft closure, maxillary distraction, and autogenous bone grafting. The combined simultaneous approach is extremely advantageous in correcting severe deformities, reducing the number of surgical interventions and, consequently, the total treatment time.

A case of oculo-auriculo-vertebral spectrum with long-term and comprehensive management.

AIM: To show that a patient with severe oculo-auriculo-vertebral spectrum can achieve satisfactory occlusion and facial appearance through long-term and comprehensive management. METHODS: A patient, with oculo-auriculo-vertebral spectrum, had bilateral cleft lip and palate, macrostomia, malformed pinna, and unilateral hypoplasia of the zygomatic arch and mandible, which resulted in an asymmetric facial appearance characteristic of hemifacial microsomia. After bilateral lip repair and palatal closure, surgical repair of the pinna, nose, and cheiloplasty was performed. The patient was seen at the authors' dental hospital at 12 years 2 months of age. After lateral expansion of the maxillary arch, an edgewise multibracket appliance was placed and presurgical orthodontic treatment was begun. Combined maxillary and mandibular osteotomies were performed when the patient was 19 years of age, followed by genioplasty, multiple repair of the mandibular body and lip, and soft tissue transplantation to the left cheek, to improve facial symmetry. RESULTS AND CONCLUSION: After prosthetic treatment at 23 years of age, a stable and functional occlusion with a satisfactory facial appearance was achieved.

Functional analysis of natural mutations in two TWIST protein motifs.

The basic helix-loop-helix protein Twist, a transcriptional repressor, is essential for embryogenesis in both invertebrates and vertebrates. Haploinsufficiency of the human TWIST1 gene, which causes the craniosynostosis disorder Saethre-Chotzen syndrome (SCS), is related to failure to repress transcription of CDKN1A (which encodes p21/WAF1/CIP1), promoting osteoblast differentiation. We have examined the functional significance of natural TWIST1 variants present in craniosynostosis patients and in their healthy relatives. Both deletion and duplication variants of the glycine-rich tract Gly5AlaGly5 inhibited E2A (E12/E47)-dependent transcription of CDKN1A to a similar degree as wild-type protein, indicating that the length of this glycine tract is not critical for efficient transcriptional repression. We also evaluated a newly identified heterozygous TWIST1 variant (c.115C>G, encoding p.Arg39Gly), located within a putative nuclear localization signal (NLS), that was present in a child with mild SCS and her clinically unaffected father and grandmother. Unlike wild-type protein, this mutant required cotransfected E12 to localize to the nucleus, indicating that the NLS, including amino acid 39, is essential for nuclear localization; inhibition of E2A-dependent transcription of CDKN1A occurred normally. This analysis further dissects the structure-function relationships of TWIST and corroborates with phenotypic observations of disease expressivity.

Craniofacial morphology of skeletal class III patients before treatment and growth-related changes during treatment with a maxillary protraction appliance: a comparison of orthodontic and surgical cases.

AIMS: To examine differences in the craniofacial morphology of skeletal Class III patients before treatment and growth-related changes during treatment with a maxillary protraction appliance (MPA) between patients who were treated only orthodontically (orthodontic group) and those who eventually received orthognathic surgery (surgical group). METHODS: The orthodontic and surgical groups consisted of 6 boys and 9 girls and 4 boys and 6 girls, respectively. Lateral cephalograms taken at the first visit and at the end of treatment with the MPA were measured. The Mann-Whitney U test and Wilcoxon signed-rank test were used. RESULTS: Before treatment, the Wits appraisal was significantly smaller and the gonial angle was significantly larger in the surgical group. During treatment, both the SNA and ANB angles were significantly increased in the orthodontic group, whereas only the SNB angle was significantly increased in the surgical group. Moreover, significant lingual inclination of the mandibular incisors was found in the orthodontic group. CONCLUSION: The Wits appraisal and gonial angle were useful for distinguishing between the two groups at the first visit. Facilitation of forward maxillary growth, modification of the direction of mandibular growth, and lingual tipping of the mandibular incisors may be important ways to avoid orthognathic surgery.

Evaluation of stomatognathic function in orthodontic treatment.

AIM: To evaluate changes in stomatognathic function related to orthodontic treatment in 4 patients with various types of dysfunction of the stomatognathic system present prior to orthodontic treatment. METHODS: Four patients who visited the Orthodontic Clinic at Tokyo Medical and Dental University Hospital and whose active orthodontic treatment was complete were analyzed both morphologically and functionally. To analyze stomatognathic function, electromyographic activity of the masticatory muscles and mandibular movements was recorded. RESULTS: In all 4 patients, changes in stomatognathic function were observed following improvements in craniofacial structural and interocclusal relationships. Many of these changes consisted of elimination of functional disharmony, although the cause-effect relationship between these functional changes and orthodontic treatment is unclear. CONCLUSION: Functional analysis during orthodontic treatment can provide useful information concerning the relationship between craniofacial structures and stomatognathic function.

Effects of mandibular advancement on supine airway size in normal subjects during sleep.

STUDY OBJECTIVES: To examine changes in the upper-airway dimension and its surrounding structures induced by mandibular advancement during sleep. DESIGN: Eleven nonapneic adult males participated in the study. A set of supine lateral cephalograms was taken for each subject at the end of expiration during stage 1 and 2 non-rapid-eye-movement sleep with and without a Klearway appliance (Great Lakes Orthodontics, NY, USA), which was adjusted to 67% of the maximum protrusion position. The Wilcoxon signed-rank test was used to compare changes in the anteroposterior width of the upper airway and the positions of the hyoid bone and third cervical vertebra with and without the appliance. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The amount of jaw opening was significantly increased by wearing the titratable oral appliance, and the mandibular symphysis moved backward. The sagittal dimension of the superior pharyngeal airway was significantly increased; however, no significant changes were found in the middle and inferior pharyngeal airway. Significant posterior displacement of the hyoid bone and third cervical vertebra was seen. Moreover, significant inferior displacement of the hyoid bone was also seen. The relationship among the mandibular symphysis, the hyoid bone, and the third cervical vertebra remained constant. CONCLUSIONS: Mandibular advancement significantly increases the size of the upper airway in the velopharynx and results in posteroinferior displacement of the hyoid bone and posterior displacement of the third cervical vertebra during sleep.

Mandibular coronoid process in parathyroid hormone-related protein-deficient mice shows ectopic cartilage formation accompanied by abnormal bone modeling.

Parathyroid hormone-related protein (PTHrP) null mutant mice were analyzed to investigate an additional role for PTHrP in cell differentiation. We found ectopic cartilage formation in the mandibular coronoid process in newborn mice. While many previous studies involving PTHrP gene knockout mouse have shown that the cartilage in various regions becomes smaller, this is the first report showing an "increase" of cartilage volume. Investigations of mandibular growth using normal mice indicated that coronoid secondary cartilage never formed from E 15 to d 4, but small amount of cartilage temporally formed at d 7, and this also applies to PTHrP-wild type mice. Therefore, PTHrP deficiency consequently advanced the secondary cartilage formation, which is a novel role of PTHrP in chondrocyte differentiation. In situ hybridization of matrix proteins showed that this coronoid cartilage had characteristics of the lower hypertrophic cell zone usually present at the site of endochondral bone formation and/or "chondroid bone" occasionally found in distraction osteogenesis. In addition, the coronoid process in the PTHrP-deficient mouse also showed abnormal expansion of bone marrow and an increase in the number of multinucleated osteoclasts, an indication of abnormal bone modeling. These results indicate that PTHrP is involved in bone modeling as well as in chondrocyte differentiation. In situ hybridization of matrix protein mRNAs in the abnormal mandibular condylar cartilage revealed that this cartilage was proportionally smaller, supporting previous immunohistochemical results.

Delayed tooth eruption and suppressed osteoclast number in the eruption pathway of heterozygous Runx2/Cbfa1 knockout mice.

Genetic studies have recently identified a mutation of one allele of runt-related gene 2 (RUNX2/CBFA1) as the cause for an autosomal-dominant skeletal disorder, cleidocranial dysplasia (CCD), which is characterised by hypoplasia of the clavicles and calvariae and widened sutures and fontanelles. In addition, CCD is frequently affected with multiple supernumerary teeth and the impaction and delayed eruption of teeth, the causes of all these dental abnormalities are still unknown. To clarify the cellular mechanism of the delayed tooth eruption in CCD, the process of tooth eruption was examined in heterozygous Runx2/Cbfa1 (mouse homolog of RUNX2/CBFA1) knockout mice, known to mimic most of the bone abnormalities of CCD. The timing of the appearance of maxillary and mandibular teeth into the oral cavity was significantly delayed in heterozygous mutant mice compared with wild-type mice. From postnatal days 8 to 10, an active alveolar bone resorption and a marked increase of the osteoclast surfaces was observed in the eruption pathway of both genotypes, but this increase was significantly suppressed in the mutant mice. In contrast, the osteoclast surfaces did not show a significant difference between the two genotypes in the future cortical area of femora. These results suggest that haploinsufficiency of Runx2/Cbfa1 does not effect the femoral bone remodelling but is insufficient for the active alveolar bone resorption essential for the prompt timing of tooth eruption. These results also suggest the possibility that impaired recruitment of osteoclasts is one of the cellular mechanisms of delayed tooth eruption in CCD patients.

An in-vivo experimental model for studying wound-healing after laser irradiation in the mouse foetus.

OBJECTIVE: The purpose of this study was to develop an experimental model to study wound-healing in the mouse foetus by inducing an injury with an argon laser. MATERIAL AND METHODS: ICR strain mouse dams were used in this study at day 14 of gestation. Laparotomy was performed on the dams under sodium pentobarbital anaesthesia, and foetuses were exposed from the uterus while wrapped in the amnion. Laser radiation was conducted through the amniotic membrane, and the beam was focused on to the naso-labial region. After laser irradiation, the foetus was returned to the abdominal cavity of the dam. Then the abdominal wall was closed, and an extrauterine pregnancy was maintained. Foetuses were sacrificed at intervals and wound healing was examined histologically. RESULTS: Immediately after laser irradiation, the foetal epithelium was detached and degeneration of the epithelium and subepithelial mesenchymal tissue were observed. Twenty-four hours after laser irradiation, normal epithelial cells surrounding the wound began to migrate along the margin of the degenerate tissue mass. By seventy-two hours after laser irradiation, the laser-induced wound had recovered, and scar formation was not observed. CONCLUSION: The application of an argon laser allowed to inflict a wound on a mouse foetus without damaging the amnion, and this experimental model appeared to be useful for studying the mechanism of foetal wound-healing.

Soft tissue profile changes of the midface in patients with cleft lip and palate following maxillary distraction osteogenesis: a preliminary study.

OBJECTIVE: The purpose of this study was to examine preoperative to postoperative changes of soft tissue profiles in the midface of cleft patients who underwent maxillary distraction. STUDY DESIGN: Nine cleft patients were examined (distraction group). Lateral cephalograms were obtained preoperatively and 6 months after distraction. Changes in the positions of soft and hard tissue landmarks, the nasolabial angle, and facial height were investigated and compared with those in 9 other cleft patients who underwent conventional maxillary advancement (conventional group). RESULTS: Anterior changes of the soft and hard tissue landmarks were significantly larger in the distraction group than in the conventional group. The distraction group tended to have larger increases in the nasolabial angle and subnasal length, as well as a higher anterior movement ratio for soft to hard tissue. CONCLUSIONS: These results suggest that, in the midfacial profile changes of cleft patients who underwent maxillary distraction, not only is advancement of soft and hard tissue large, but also anterior movement ratio for soft to hard tissue is relatively high.

Longitudinal dento-skeletal changes in UCLP patients following maxillary distraction osteogenesis using RED system.

Longitudinal dento-skeletal changes in unilateral cleft lip and palate (UCLP) patients following maxillary distraction osteogenesis using the rigid external distraction device (RED) were analyzed. Twelve Japanese non-syndromic UCLP patients who underwent maxillary distraction at the mean age of 16.4 years were used as subjects. Serial sets of lateral cephalograms, taken at 4 stages: 1) before osteotomy, 2) immediately after distraction, 3) 6 months and 4) 12 months post-osteotomy, were analyzed. Statistical analyses, including a paired t test, Pearson correlation analysis and stepwise linear regression analysis, were performed to distill characteristic dento-skeletal changes. In accordance with maxillary advancement, significant amounts of up-forward movement of the nasal bone, mandibular rotation and maxillary dental changes were observed. Maxillary dental changes were significantly related to the amount of mandibular rotation and force system of maxillary traction. Significant dento-skeletal relapse was found to occur during the 0-to-6-month follow-up period, but not in the 6-to-12-month follow-up period. Maxillary relapse was significantly related to the amount of maxillary advancement and severity of pre-surgical maxillary hypoplasia, while mandibular relapse was significantly related to maxillary dento-skeletal relapse. Successful clinical application of this procedure therefore requires consideration of both the surrounding dento-skeletal changes and the traction force system.

Comparison of fMRI data analysis by SPM99 on different operating systems.

The hardware chosen for fMRI data analysis may depend on the platform already present in the laboratory or the supporting software. In this study, we ran SPM99 software on multiple platforms to examine whether we could analyze fMRI data by SPM99, and to compare their differences and limitations in processing fMRI data, which can be attributed to hardware capabilities. Six normal right-handed volunteers participated in a study of hand-grasping to obtain fMRI data. Each subject performed a run that consisted of 98 images. The run was measured using a gradient echo-type echo planar imaging sequence on a 1.5T apparatus with a head coil. We used several personal computer (PC), Unix and Linux machines to analyze the fMRI data. There were no differences in the results obtained on several PC, Unix and Linux machines. The only limitations in processing large amounts of the fMRI data were found using PC machines. This suggests that the results obtained with different machines were not affected by differences in hardware components, such as the CPU, memory and hard drive. Rather, it is likely that the limitations in analyzing a huge amount of the fMRI data were due to differences in the operating system (OS).

Immunohistochemical localization of matrix metalloproteinase 13 (MMP-13) in mouse mandibular condylar cartilage.

MMP-13 appears to be one of the most important MMPs in cartilage remodeling and mineralization, because it exhibits a substrate preference for the cartilage-specific type II collagen. The condylar process is constructed by rapid accumulation of hypertrophic chondrocytes during development, but its mechanism is still unclear. To investigate the role of MMP-13 in developing condylar cartilage, we immunohistochemically examined the localization of MMP-13 in the endochondral ossification of the mandibular condyle and tibiae of newborn mice. In the tibiae, the MMP-13 expression was detected only in the deepest layer of the terminal hypertrophic chondrocytes through every examined stage (day 1 to day 10 after birth). On the other hand, in the condylar cartilage at days 1 and 5, MMP-13 was expressed throughout the proliferating and the hypertrophic chondrocytes, and at day 10, MMP-13 was mainly localized in the deepest edge of the hypertrophic layer. A zymographical study showed that the activity of MMP-13 in the condyle was observed at day 1, earlier than in the tibia, and increased until day 7. The time-dependent and cell-specific expression of MMP-13 and its enzymatic property suggest that in the mandibular condylar cartilage, MMP-13 plays a role in making the space for cell enlargement by degradation of the cartilage matrix and in onset of mineralization during the early stage of development.

Effects of experimental nasal obstruction on human masseter and suprahyoid muscle activities during sleep.

The effect of nasal obstruction on nocturnal masseter and suprahyoid muscle activities using a newly developed portable electromygram (EMG)-recording unit was examined. Ten healthy Japanese males participated in this study. EMG activities of both the right masseter and bilateral suprahyoid muscles were recorded with a portable EMG-recording unit. At midnight, the subject was asked to lie on a bed after complete preparation with surface electrodes. After maximal clenching and jaw-opening effort (100% maximum voluntary contribution), the subject was allowed to fall asleep. In the first half of the night, EMG activities were recorded for about three hours of sleep without nasal obstruction. In the second half of the night, EMG activities were recorded for about three hours of sleep with nasal obstruction. In both muscles, there were no significant changes in either the maximal EMG activities or the number of events beyond 40% MVC with nasal obstruction. But in an evaluation based on the distribution of muscle activities, the EMG activity of the masseter muscle tended to decrease (P = .07) and that of the suprahyoid muscles increased significantly (P = .02) with nasal obstruction. These results suggest that nasal obstruction could modulate the activities of the masseter and suprahyoid muscles during sleep.

Relationship between formation and eruption of permanent mandibular buccal dentition and vertical height of the mandibular body: longitudinal study of Japanese boys from 4 to 9 years of age.

AIM: To examine the relationship between the formation and eruption (vertical tooth movement in and through the alveolar bone) of the permanent mandibular buccal dentition and vertical height of the mandibular body. METHOD: Mandibular morphology and tooth formation and eruption were analyzed from cephalograms taken annually on each birthday month from 4 to 9 years of age. RESULTS: From 4 to 6 years of age, before active tooth eruption, there was a significant positive correlation between the vertical height of the mandibular body and the distance from the permanent mandibular buccal dentition to the occlusal plane. There was a significant positive correlation between the vertical height of the mandibular body at 6 years of age and the subsequent annual amount of tooth eruption in the mandibular buccal dentition. Simple linear regression equations were obtained to predict the amount of mandibular buccal tooth formation and eruption from the vertical height of the mandibular body at 6 years of age. CONCLUSION: The larger the mandibular vertical height, the larger the distance from the buccal dentition to the occlusal plane before active eruption, and the larger the amount of tooth eruption during the active eruption period. The vertical mandibular morphology is useful to predict the formation and eruption of the mandibular buccal dentition.