Differences in dentofacial morphology in children with sleep disordered breathing are detected with routine orthodontic records.

BACKGROUND: Residual snoring in children with obstructive sleep disordered breathing (SDB) may continue post-adenotonsillectomy. This study aims to identify baseline dentofacial differences in children with SDB using routine orthodontic records that might aid effective early intervention for the upper airway to prevent continued obstruction. METHODS: Children (6-16 years) with clinically diagnosed SDB from a paediatric Otolaryngology Clinic who required adenotonsillectomy were participants (n = 10). The control group (n = 9) comprised healthy non-snoring children from the community. Baseline overnight polysomnography (PSG), standardised frontal and right profile photographs and alginate impressions were taken of all children. Facial width, length, depth, convexity and mandibular position were measured from the photographs. The occlusion, arch width, arch depth, maxillary arch form, palatal height and volume were recorded from digitised dental models. Inter-group differences were compared. RESULTS: SDB patients had a significantly increased lower face height, maxillo-mandibular angle (1.73°; 95% CI 0.45-3.0) and a narrower maxillary arch in the upper posterior region. There was a trend towards a decreased palatal volume, increased posterior crossbite and Class II molar relationship. CONCLUSION: Dentofacial phenotypic differences between children with SDB and controls can be detected using facial photographs and dental models. Increased awareness of these features may help to identify children who to continue to snore post adenotonsillectomy.

A qualitative investigation of RANKL, RANK and OPG in a rat model of transient ankylosis.

INTRODUCTION: Previous studies have found ankylosis occurs as a part of the inflammatory process of aseptic root resorption initiated in a rat model. The physiologic mechanisms behind the development of dentoalveolar ankylosis and healing response are still unclear. While receptor activator of nuclear factor-κß ligand (RANKL), receptor activator of nuclear factor-κß (RANK) and osteoprotegerin (OPG) have gained momentum in the understanding of resorption, no study to date has investigated their role in dentoalveolar ankylosis. AIMS: The aims of this study were to investigate if, and when, ankylosis occurred in the rat PDL, whether the resolution of ankylosis occurred with time and, finally, to observe the expression of RANKL, RANK and OPG during the ankylotic process. MATERIALS AND METHODS: Dry ice was applied for 20 minutes to the upper right first molar crown of 15 eight-week-old, male Sprague-Dawley rats. An additional three rats served as untreated external controls. Groups of three rats were sacrificed after the thermal insult on day 0, 4, 7, 14 and 28 respectively. Each maxilla was dissected out and processed for histological examination and RANKL, OPG and RANK immunohistochemistry. RESULTS: By the use of light microscopy and H&E staining, no ankylosis was detected in the external control group and the experimental groups at days 0 and 4. On day 7, disruption within the periodontal ligament was observed in the interradicular region and the initial signs of ankylosis were seen in the form of finger-like projections extending from the alveolar bone towards the cementum. Fourteen days after the thermal insult, all animals exhibited extensive ankylosis that spanned the entire interradicular periodontal space. At 28 days, the development of ankylosis appeared to have ceased and repair was observed, together with an intact periodontal ligament in all but one rat. Positive staining results were obtained with RANKL, RANK and OPG antibodies. The expressions of RANKL, RANK and OPG were similar in the external control group, 0-, 4-, and 28-day experimental groups. In the 7- and 14-day experimental groups, RANKL, RANK and OPG were expressed in the blood vessels within the ankylotic regions. CONCLUSIONS: During the development of ankylosis and its resolution, it was concluded from their simultaneous presence that there is a complex interaction between RANKL, RANK and OPG that requires further investigation.

Accelerating orthodontic tooth movement with the aid of periodontal surgery--the practitioner viewpoint.

INTRODUCTION: There has been a revival of interest in the acceleration of orthodontic tooth movement (OTM) by inducing injury to dentoalveolar cortical bone. Termed corticotomy, the procedure offers an advantage to adult patients whose bone metabolism is such that any reduction in treatment time would be welcomed. The procedure has been refined for over 100 years and recent research indicates treatment duration may be reduced often by as much as a third, but it is not clear how widely the method is applied in practice. For the procedure to be successful, careful interdisciplinary management by orthodontists and periodontists is required. However, information regarding the attitude and knowledge of practitioners and the frequency of the procedure performed in Australia and New Zealand is lacking. METHODS: A questionnaire was formulated and tested in a pilot study on postgraduate orthodontic and periodontic students at The University of Adelaide. As a consequence of the responses, the wording of several questions was clarified and the sequence modified to produce the final format. Separate questionnaires were developed for specialist orthodontists and periodontists in keeping with their different backgrounds and were distributed at two relevant conferences. RESULTS AND CONCLUSIONS: The number of practitioners who had been involved with at least one corticotomy per annum was low for orthodontists (12%) and periodontists (18%). The majority of those surveyed believed that more research was required on corticotomy-facilitated OTM and would not recommend the procedure to patients without greater investigation of the technique. More than half of the sampled orthodontists indicated that they would never recommend corticotomy-facilitated orthodontics to their patients. The minority who were willing to recommend the procedure would limit involvement to adult patients, the management of ankylosed teeth, impacted canines and patients susceptible to root resorption. Over 90% of the sampled periodontists believed that there were adverse side effects.

Craniofacial and upper airway morphology in pediatric sleep-disordered breathing and changes in quality of life with rapid maxillary expansion.

INTRODUCTION: The association between pediatric sleep-disordered breathing caused by upper airway obstruction and craniofacial morphology is poorly understood and contradictory. The aims of this study were to evaluate the prevalence of children at risk for sleep-disordered breathing, as identified in an orthodontic setting by validated screening questionnaires, and to examine associations with their craniofacial and upper airway morphologies. A further aim was to assess the change in quality of life related to sleep-disordered breathing for affected children undergoing rapid maxillary expansion to correct a palatal crossbite or widen a narrow maxilla. METHODS: A prospective case-control study with children between 8 and 17 years of age (n = 81) at an orthodontic clinic was undertaken. The subjects were grouped as high risk or low risk for sleep-disordered breathing based on the scores from a validated 22-item Pediatric Sleep Questionnaire and the Obstructive Sleep Apnea-18 Quality of Life Questionnaire. Variables pertaining to a screening clinical examination, cephalometric assessment, and dental cast analysis were tested for differences between the 2 groups at baseline. Ten children who underwent rapid maxillary expansion were followed longitudinally until removal of the appliance approximately 9 months later with a repeated Obstructive Sleep Apnea-18 Quality of Life Questionnaire. All data were collected blinded to the questionnaire results. RESULTS: The frequency of palatal crossbite involving at least 3 teeth was significantly higher in the high-risk group at 68.2%, compared with the low-risk group at 23.2% (P <0.0001). Average quality of life scores in the high-risk group indicated reduced quality of life related to sleep-disordered breathing by 16% compared with children in the low-risk group at baseline (P <0.0001). Cephalometrically, mean inferior airway space, posterior nasal spine to adenoidal mass distance, and adenoidal mass to soft palate distance were reduced in the high-risk group compared with the low-risk group by 1.87 mm (P <0.03), 2.82 mm (P <0.04), and 2.13 mm (P <0.03), respectively. The mean maxillary intercanine, maxillary interfirst premolar, maxillary interfirst molar, mandibular intercanine, and mandibular interfirst premolar widths were reduced in the high-risk group compared with the low-risk group by 4.22 mm (P <0.0001), 3.92 mm (P <0.0001), 4.24 mm (P <0.0001), 1.50 mm (P <0.01), and 1.84 mm (P <0.01), respectively. Children treated with rapid maxillary expansion showed an average improvement of 14% in quality of life scores in the high-risk group compared with the low-risk group, which showed a slight worsening in quality of life related to sleep-disordered breathing by an average of 1% (P <0.04), normalizing the quality of life scores in the high-risk children to the baseline scores compared with the low-risk group. CONCLUSIONS: Children at high risk for sleep-disordered breathing are characterized by reduced quality of life, reduced nasopharyngeal and oropharyngeal sagittal dimensions, palatal crossbite, and reduced dentoalveolar transverse widths in the maxillary and mandibular arches. No sagittal or vertical craniofacial skeletal cephalometric predictors were identified for children at high risk for sleep-disordered breathing. In the short term, rapid maxillary expansion might aid in improvement of the quality of life for children with a narrow maxilla in the milder end of the sleep-disordered breathing spectrum.

Craniofacial and upper airway morphology in pediatric sleep-disordered breathing: Systematic review and meta-analysis.

INTRODUCTION: Pediatric sleep-disordered breathing is a continuum, with primary snoring at one end, and complete upper airway obstruction, hypoxemia, and obstructive hypoventilation at the other. The latter gives rise to obstructive sleep apnea. An important predisposing factor in the development and progression of pediatric sleep-disordered breathing might be craniofacial disharmony. The purpose of this systematic review and meta-analysis was to elucidate the association between craniofacial disharmony and pediatric sleep-disordered breathing. METHODS: Citations to potentially relevant published trials were located by searching PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. The MetaRegister of controlled trials database was also searched to identify potentially relevant unpublished trials. Additionally, hand-searching, Google Scholar searches, and contact with experts in the area were undertaken to identify potentially relevant published and unpublished studies. Inclusion criteria were (1) randomized controlled trials, case-control trials, or cohort studies with controls; (2) studies in nonsyndromic children 0 to 18 years of age with a diagnosis of sleep-disordered breathing or obstructive sleep apnea by either a sleep disorders unit, screening questionnaire, or polysomnography; and (3) principal outcome measures of craniofacial or upper airway dimensions or proportions with various modalities of imaging for the craniofacial and neck regions. The quality of the studies selected was evaluated by assessing their methodologies. Treatment effects were combined by meta-analysis with the random-effects method. RESULTS: Children with obstructive sleep apnea and primary snoring show increased weighted mean differences in the ANB angle of 1.64° (P <0.0001) and 1.54° (P <0.00001), respectively, compared with the controls. An increased ANB angle was primarily due to a decreased SNB angle in children with primary snoring by 1.4° (P = 0.02). Children with obstructive sleep apnea had a distance from the posterior nasal spine to the nearest adenoid tissue measured along the PNS-basion line reduced by 4.17 mm (weighted mean difference) (P <0.00001) and a distance from the posterior nasal spine to the nearest adenoid tissue measured along the line perpendicular to the sella-basion line reduced by 3.12 mm (weighted mean difference) (P <0.0001) compared with the controls. CONCLUSIONS: There is statistical support for an association between craniofacial disharmony and pediatric sleep-disordered breathing. However, an increased ANB angle of less than 2° in children with obstructive sleep apnea and primary snoring, compared with the controls, could be regarded as having marginal clinical significance. Therefore, evidence for a direct causal relationship between craniofacial structure and pediatric sleep-disordered breathing is unsupported by this meta-analysis. There is strong support for reduced upper airway width in children with obstructive sleep apnea. Larger well-controlled trials are required to address the relationship of craniofacial and upper airway morphology to pediatric sleep-disordered breathing in all 3 dimensions.

Paediatric sleep-disordered breathing due to upper airway obstruction in the orthodontic setting: a review.

The essential feature of paediatric sleep-disordered breathing (SDB) is increased upper airway resistance during sleep presenting clinically as snoring. Paediatric SDB is a continuum ranging from primary snoring (PS), which is not associated with gas exchange abnormalities or significant sleep fragmentation, to obstructive sleep apnoea (OSA) with complete upper airway obstruction, hypoxaemia, and obstructive hypoventilation. Adenotonsillar hypertrophy, obesity and craniofacial disharmonies are important predisposing factors in the development and progression of paediatric SDB. Clinical symptoms are significant and domains affected include behaviour, neurocognition, cardiovascular morbidity and quality of life. Overnight polysomnography is the current diagnostic gold standard method to assess SDB severity while adenotonsillectomy is the recommended first line of treatment. Other treatments for managing paediatric SDB include nasal continuous airway pressure, the administration of nasal steroids, dentofacial orthopaedic treatment and surgery. However, there are insufficient long-term efficacy data using dentofacial orthopaedics to treat paediatric SDB. Further studies are warranted to define the characteristics of patients who may benefit most from orthodontic treatment.

Facial aesthetics and perceived need for further treatment among adults with repaired cleft as assessed by cleft team professionals and laypersons.

The objectives of this study were to compare the ratings of professionals and laypeople with and without a cleft regarding the facial aesthetics of adult patients previously treated for orofacial clefting. The necessity for further treatment, as perceived by the respective groups, is also compared. The design of the study was a cross-sectional study. Professionals (two plastic surgeons, one dentist, one orthodontist, and one psychologist) and laypeople (one male and one female adult without a cleft and one male and one female adult with a cleft) were recruited to rate photographs of 80 non-syndromic cleft patients treated by the Australian Craniofacial Unit from 1975 to 2009. Facial aesthetics were measured by a visual analogue scale (VAS; 0-100 mm). High values indicated good aesthetics. Necessity for further treatment was also measured by a VAS (0-100 mm). High values indicated high perceived need for further treatment. The professionals rated facial aesthetics significantly lower and had a lower perception of need for further treatment than the raters with and without a cleft. The laypeople with a cleft rated facial aesthetics significantly higher and had a lower perceived need for further treatment than laypeople without a cleft. The non-surgical professionals rated facial aesthetics significantly lower and had a lower perceived need for further treatment than the surgical professionals. Differences exist in the facial aesthetics ratings and perceived need for further surgery between professionals and laypeople with and without a cleft. This should be considered when managing cleft treatment expectations.

The effects of hypothermia and L-arginine on skeletal muscle function in ischemia-reperfusion injury.

OBJECTIVES: Ischemia-reperfusion (I/R) injury can have detrimental effects on skeletal muscle. We have shown that vessel permeability can be minimized in a hypothermic setting and also by administering the nitric oxide synthase (NOS) stimulator, L-arginine, at physiologic temperatures. The purpose of this study was to examine and compare skeletal muscle contractility after an I/R insult during hypothermic conditions, warm conditions, and also with the administration of L-arginine at physiologic temperatures. We hypothesized that hypothermia and L-arginine administration will also demonstrate protective effects to skeletal muscle contractility. METHODS: Using Sprague-Dawley rats, the extensor digitorum longus muscle was rotated on its vascular pedicle to a thermo-controlled stage. Ischemia was established using an atraumatic femoral artery tourniquet. Reperfusion was performed under control and experimental conditions including local hypothermia and intravenous L-arginine. After harvesting experimental muscles, contractility was then quantified by using a tissue bath stimulator with force transducers. RESULTS: Warm reperfusion resulted in marked decrease in muscle contractility compared with sham animals. Local hypothermia showed statistically significant preservation of contractility compared with the sham group. This protective effect was recapitulated by the application of NOS inducers (L-arginine) at warm conditions. CONCLUSIONS: These findings demonstrate that hypothermia and L-arginine are protective of skeletal muscle contractility after an I/R injury. The results presented may have profound effects on future therapeutic recommendations and suggest possible pathways for clinical intervention to modulate I/R injury, which is commonplace in orthopaedic trauma and reconstructive surgery.

A pharmacodynamic investigation into the efficacy of osteoprotegerin during aseptic inflammation.

BACKGROUND: Osteoprotegerin (OPG), as an osteoclast antagonist, limits mineralised tissue resorption under physiological conditions. Previous work investigating OPG in a rat periodontal ligament (PDL) ankylosis model found no inhibitory effect on osteoclasts when OPG was administered at a dosage of 2.5mg/kg. AIMS: The object of this study was to determine whether dosages higher than 2.5 mg/kg of OPG were required to limit osteoclastic activity in an aseptic inflammatory model in rats. MATERIALS AND METHODS: Dry ice was applied for 15 minutes to the upper right first molar crown of eighteen, 8-week-old, male Sprague-Dawley rats. Three groups of 3 were injected with OPG at dosages of 2.5, 5.0 and 7.5 mg/kg of body weight immediately following the thermal insult. After 7 days, the rats were sacrificed and each maxilla processed for histological examination and stained for osteoclastic activity using tartrate-resistant acid phosphatase (TRAP). Osteoclast population numbers were estimated via light microscopy and results were analysed using a comparative mixed model statistical analysis. RESULTS: Results showed OPG inhibited osteoclastic activity in a dose-dependent manner. From 2.5 mg/kg to 7.5 mg/kg, osteoclast populations were linearly reduced by 39.78% (p < 0.05). OPG did not appear to affect the inflammatory process and had varied efficacy in different regions of individual teeth. CONCLUSION: Although osteoclastic activity reduced, it was not completely eliminated, perhaps because dosages were still inadequate, or additional factors might influence OPG and osteoclast activation in the aseptic inflammatory model.

The presence of TNF-alpha and TNFR1 in aseptic root resorption. A preliminary study.

BACKGROUND: It is hypothesised that osteoprotegerin (OPG), as an osteoclast antagonist, may offer molecular control over the process of orthodontic root resorption. Previous work investigating OPG in a rat periodontal ligament (PDL) ankylosis model found no inhibitory effect on osteoclasts and odontoclasts when given at a recommended dosage of 2.5 mg/kg. It was considered that traumatically-induced PDL inflammation produces mediators and cytokines with the ability to stimulate clast cell differentiation and counter the effects of OPG. AIMS: The present study investigated the presence of Tumour Necrosis Factor Alpha (TNF-alpha) and its receptor Tumour Necrosis Factor Receptor 1 (TNFR1) in a PDL sterile inflammatory model. METHODS: Dry ice was applied for 15 minutes to the upper right first molar crown of eighteen, 8-week-old, male Sprague-Dawley rats of which 9 were injected with OPG at a dose of 2.5 mg/kg of body weight at the time of freezing. After 7 days, the rats were sacrificed and each maxilla processed for immunohistochemical identification of TNF-alpha and TNFR1. RESULTS: Results showed the presence of root resorption in varying amounts and locations in both experimental and control rats. Reparative processes appeared greater in the OPG-treated rats, often with the presence of an ankylotic union. Immunolabelling showed the presence of TNF-alpha and TNFR1 in the sterile inflammation located mainly in the interradicular PDL area. More definitive labelling appeared in OPG-treated rats. CONCLUSION: The results indicated that TNF-alpha, and its receptor TNFR1, by their presence, may modify OPG effectiveness by offering an alternative pathway for osteoclast formation, which counters the anti-resorptive effects of OPG.

MicroRNAs: master regulators of ethanol abuse and toxicity?

Ethanol exerts complex effects on human physiology and health. Ethanol is not only addictive, but it is also a fetal teratogen, an adult neurotoxin, and an etiologic agent in hepatic and cardiovascular disease, inflammation, bone loss, and fracture susceptibility. A large number of genes and signaling mechanisms have been implicated in ethanol's deleterious effects leading to the suggestion that ethanol is a "dirty drug." An important question is, are there cellular "master-switches" that can explain these pleiotropic effects of ethanol? MicroRNAs (miRNAs) have been recently identified as master regulators of the cellular transcriptome and proteome. miRNAs play an increasingly appreciated and crucial role in shaping the differentiation and function of tissues and organs in both health and disease. This critical review discusses new evidence showing that ethanol-sensitive miRNAs are indeed regulatory master-switches. More specifically, miRNAs control the development of tolerance, a crucial component of ethanol addiction. Other drugs of abuse also target some ethanol-sensitive miRNAs suggesting that common biochemical mechanisms underlie addiction. This review also discusses evidence that miRNAs mediate several ethanol pathologies, including disruption of neural stem cell proliferation and differentiation in the exposed fetus, gut leakiness that contributes to endotoxemia and alcoholic liver disease, and possibly also hepatocellular carcinomas and other gastrointestinal cancers. Finally, this review provides a perspective on emerging investigations into potential roles of miRNAs as mediators of ethanol's effects on inflammation and fracture healing, as well as the potential for miRNAs as diagnostic biomarkers and as targets for therapeutic interventions for alcohol-related disorders.

Immunohistochemical detection of nerve growth factor and its receptors in the rat periodontal ligament during tooth movement.

OBJECTIVES: Nerve growth factor (NGF) and its receptors, p75 and tyrosine receptor kinase A (Trk A), have been shown to increase following trauma. The aims of this study were to examine changes in the detection of NGF and its receptors during orthodontic tooth movement in the rat, and the effects of anti-NGF on these changes. DESIGN: Orthodontic separators were placed between the right maxillary first and second molars of Sprague-Dawley rats which were equally divided into two groups. Animals from the second group were injected with anti-NGF. The left sides served as controls, and animals were sacrificed at 0, 3, 7 and 14 days. RESULTS: Results of immunohistochemical localisation for p75, Trk A, calcitonin gene-related peptide (CGRP) and NGF showed staining intensity increased at day 3, with a peak at day 7 and decreasing intensity at day 14. Anti-NGF injected animals showed reduced staining at all observation periods. CONCLUSION: Data suggest that orthodontic injury induces NGF production, leading to sprouting and invasion by CGRP-positive nerve fibers and that injection of anti-NGF reduces NGF tissue levels and prevents innervation by CGRP-positive fibers.

Distribution of the epithelial rests of Malassez and their relationship to blood vessels of the periodontal ligament during rat tooth development.

BACKGROUND: There is some evidence that the epithelial cell rests of Malassez partition the root surface from the periodontal ligament blood vessels, and may protect the root from resorption. OBJECTIVE: The aim of the present study was to determine the distributions of the epithelial rests of Malassez (ERM) and blood vessels in the periodontal ligament (PDL) of the developing rat first molar before, during and after emergence. METHODS: Four Sprague-Dawley rats were sacrificed at two days, one week, two weeks, three weeks, four weeks and six weeks of age. After processing, the maxillae were embedded in paraffin, and sectioned longitudinally and transversely. The sections were stained with a double immuno-histochemical technique which utilised a keratin antibody AE1-AE3 (1:2,000) and an endothelial antibody Factor VIII (1:10,000) to enable simultaneous labelling of ERM and blood vessels. ERM and blood vessel counts were obtained from the mesio-buccal roots of three week, four week and six week-old rats, whilst qualitative observations were made for the earlier developmental stages. RESULTS: ERM cells and cell clusters were found in the tooth third of the PDL width at the three, four and six week stages. Cells and cell clusters increased in number with age, especially in the upper third of the mesio-buccal root. The largest numbers of cells and clusters were found on the distal surfaces of the roots in all age groups. Cells and clusters in all root surfaces increased from three to four weeks, but decreased from four to six weeks. The greatest number of blood vessels was found in the bone-side third of the PDL. The distal surface had the highest proportion of blood vessels, and the palatal surface the least proportion. The number of blood vessels in all surface quadrants did not vary much from three to four weeks of age, but increased from four to six weeks of age, possibly as a reaction to tooth emergence and occlusal function. Physiological root resorption was only observed after tooth emergence, and appeared to be related to loss of continuity of the ERM network and the incursion of blood vessels. CONCLUSIONS: Orthodontic root resorption can be regarded as an exaggerated response to loss of PDL homeostatic control, possibly mediated by the epithelial rests of Malassez.

Syndecan-1 expression during postnatal tooth and oral mucosa development in rats aged from two days to six weeks.

Syndecans are a family of heparan sulphate proteoglycans that regulate cell-matrix interactions that influence cell growth, proliferation and morphology. The aim of this study was to observe changes in the expression of Syndecan-1 in the developing epithelium of the rat oral mucosa and in the epithelial cell rests of Malassez in the developing periodontium of normal rat molars, from late crown development through to early eruption. Immuno-histochemistry (Syndecan-1 N-18) and histochemistry (Alcec Bluel were used to observe changes in the expression of Syndecon-1 in rats aged two to 42 days. Results indicated that during normal tooth development in the rat, labelling or staining of variable intensity for Syndecan-1 was demonstrated in the stratified oral epithelium above the stratum basale in the rat tongue and palate, and in ameloblasts of the developing molar in rats aged two to 14 days. Histochemical staining of the predentine and dentine layers was consistent in all specimens. Labelling or staining for Syndecan-1 was negative in the rat periodontal ligament, which may suggest that either Syndecan-1 was not expressed during normal molar root development or that continued work is required for identification of a suitable label in rats.