ORCID Profile
0000-0002-3730-4652
Current Organisations
Australian Craniofacial Unit
,
University of South Australia
,
University of Adelaide
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Publisher: Springer Science and Business Media LLC
Date: 27-02-2009
DOI: 10.1007/S00381-009-0842-6
Abstract: Ventricular shunt-induced craniosynostosis is a widely recognised cause of secondary craniosynostosis. We reviewed the management and long-term outcome of the cases of cranial deformity post cerebrospinal fluid shunting in our unit and compared these with previously published series. The Australian Craniofacial Unit and Department of Neurosurgery database was searched to identify cases of ventricular shunt-induced cranial deformity and a case note review was undertaken. Eight cases were identified, and all were shunted within 6 months of birth. Our patients required shunting with a low pressure valve for hydrocephalus secondary to either aqueduct stenosis or intraventricular haemorrhage. The diagnosis was made following computed tomography (CT) three-dimensional surface reconstruction of the skull. Two cases of confirmed suture fusion were treated with cranial vault remodelling and programmable shunt insertion. In six cases, the sutures were not completely fused on the CT images despite a scaphocephalic head shape. These patients were managed conservatively with close monitoring. Cranial vault remodelling together with insertion of programmable shunt valve is indicated in CT confirmed cases of secondary craniosynostosis.
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.BJPS.2004.12.029
Abstract: Syndromic craniosynostoses are commonly treated conditions in craniofacial units. The features of the common syndromes (Apert, Pfeiffer and Crouzon) all include craniosynostosis, mid-face hypoplasia and ocular proptosis. The craniofacial management of a child with these syndromes through to adulthood may require a number of surgical interventions to allow brain development, to provide an adequate airway, to prevent corneal ulceration and to provide a functional dental occlusion. The management of these different priorities into timed interventions in our unit is determined by established protocols. We report two cases that underwent simultaneous mid-face (Le Fort III) and fronto-orbital osteotomies followed by distraction but using different vectors to advance the upper and mid-face regions (to achieve all treatment goals) in a 12-year-old boy and a 16-year-old girl.
Publisher: SAGE Publications
Date: 05-2008
DOI: 10.1597/06-223
Abstract: Complications following maxillary Le Fort I osteotomy are rare. The authors present the rare complication of an arteriovenous malformation following such a procedure in a 25-year-old woman with a cleft lip and palate that was treated successfully with radiologically guided embolization.
Publisher: Wiley
Date: 08-03-2021
DOI: 10.1002/DVDY.322
Abstract: The highly conserved Grainyhead‐like ( Grhl ) family of transcription factors play critical roles in the development of the neural tube and craniofacial skeleton. In particular, deletion of family member Grainyhead‐like 2 ( Grhl2 ) leads to mid‐gestational embryonic lethality, maxillary clefting, abdominoschisis, and both cranial and caudal neural tube closure defects. These highly pleiotropic and systemic defects suggest that Grhl2 plays numerous critical developmental roles to ensure correct morphogenesis and patterning. Here, using four separate Cre‐lox conditional deletion models, as well as one genetic epistasis approach ( Grhl2 +/− Edn1 +/− double heterozygous mice) we have investigated tissue‐specific roles of Grhl2 in embryonic development, with a particular focus on the craniofacial skeleton. We find that loss of Grhl2 in the pharyngeal epithelium (using the Shh Cre driver) leads to low‐penetrance micrognathia, whereas deletion of Grhl2 within the ectoderm of the pharynx ( Nestin Cre ) leads to small, albeit significant, differences in the proximal‐distal elongation of both the maxilla and mandible. Loss of Grhl2 in endoderm ( Sox17‐2a iCre ) resulted in noticeable lung defects and a single instance of secondary palatal clefting, although formation of other endoderm‐derived organs such as the stomach, bladder and intestines was not affected. Lastly, deletion of Grhl2 in cells of the neural crest ( Wnt1 Cre ) did not lead to any discernible defects in craniofacial development, and similarly, our epistasis approach did not detect any phenotypic consequences of loss of a single allele of both Grhl2 and Edn1 . Taken together, our study identifies a pharyngeal‐epithelium intrinsic, non‐cell‐autonomous role for Grhl2 in the patterning and formation of the craniofacial skeleton, as well as an endoderm‐specific role for Grhl2 in the formation and establishment of the mammalian lung.
Publisher: Elsevier BV
Date: 12-1995
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2007
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2010
Publisher: Elsevier BV
Date: 07-2003
DOI: 10.1016/S1368-8375(03)00009-5
Abstract: This report describes a rare tumour, an epitheloid haemangioendothelioma affecting the lower lip. This tumour has a predilection for the head and neck region in young adults. Its potential to metastasise is well recognised, but the likelihood of this is currently uncertain. Current management is usually to locally excise the tumour and follow up, although there is a recognised risk that subsequent presentation with metastatic nodal disease can occur. We present a case occurring in the lip of an 18-year-old girl who had a sentinel node biopsy performed as a staging tool in conjunction with excision of a local recurrence. Although clinical examination and CT imaging of the head and neck found no evidence of metastatic disease, the sentinel node was found to contain metastatic tumour. The result of this unexpected finding was that she was investigated further with additional CT scanning of her chest and abdomen. Subsequently, a therapeutic modified radical neck dissection preserving the accessory cranial nerve was undertaken. After 3 years she remains well with no evidence of recurrent tumour. We believe that the consequence of undergoing sentinel node biopsy, which detected early metastatic tumour and her subsequent treatment, suggests a role for sentinel node biopsy in the management of epitheloid haemangioendothelioma.
Publisher: Wiley
Date: 2001
DOI: 10.1002/HED.1050
Abstract: Atypical fibroxanthoma occurs most frequently in the head and neck region of the elderly. Previous reports have identified that the condition usually arises at the following sites: the nose, cheeks, forehead, and the ears its development at other sites is unusual. We report a series of 10 cases with lesions all occurring at an apparently unusual site, the scalp, over a 10-year period. We compared the clinical and histologic appearances and behavior of this series with the existing reports of these lesions elsewhere in the head and neck region to investigate whether there were differences with those occurring at a conventional site. Despite the identification of a range of clinical and histologic findings in our cases, we were unable to find any significant differences with those arising at a conventional site. This clustering of cases at an apparently unusual site leads us to propose that this condition occurs more commonly on the scalp than current literature suggests. The possibility of its development at this site should be remembered by head and neck surgeons in their differential diagnosis of exophytic lesions of the scalp.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-1996
DOI: 10.1097/00001665-199607000-00005
Abstract: Studies of cervical spine anomalies in patients with Crouzon's and Apert's syndromes have shown an increased incidence of fusions in comparison with that in the normal population. Currently, only small series of patients with Pfeiffer's syndrome who exhibit abnormalities have been published. The objective was to assess the incidence and pattern of radiological cervical spine abnormalities in patients with Pfeiffer's syndrome. All cervical spine radiographs of 22 patients with a confirmed diagnosis of Pfeiffer's syndrome treated at Great Ormond Street Hospital during the last 10 years were studied. All of the radiographs were reviewed by the craniofacial team along with a pediatric radiologist with experience in the assessment of skeletal dysplasias. Radiological abnormalities included hypoplasia of the neural arches, hemivertebrae, and a "butterfly" vertebra as well as vertebral fusion. Evidence of vertebral fusion was present in 16 (73%) of cases. Fusion of both the vertebral bodies and the posterior elements were noted. C2-C3 was the level most commonly involved, although fusion was noted at all levels within the cervical spine. Block fusions involving multiple vertebrae were noted. Analysis of sequential radiographs in 11 patients revealed evidence of progression in eight patients. These results reveal an incidence of anomalies that is higher than previously reported. The older age of the patients in our study demonstrates the progressive nature of the cervical fusions in Pfeiffer's syndrome.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2007
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-1997
DOI: 10.1097/00007632-199702150-00009
Abstract: All cervical spine radiographs of 44 patients with Crouzon syndrome treated at Great Ormond Street Hospital during the past 10 years were studied. To assess the incidence and pattern of cervical spine abnormalities of patients with a confirmed diagnosis of Crouzon syndrome, but particularly regarding progressive fusion. Previous studies into the cervical spine anomalies in those with Crouzon syndrome have shown an increased incidence of congenital abnormalities compared with the normal population. There is some suggestion from previous studies that cervical spine fusions are progressive in nature. All radiographs were reviewed by the craniofacial team, along with a single pediatric radiologist with experience in assessment of skeletal dysplasias. Radiologic abnormalities included "butterfly" vertebrae and fusions of the bodies and the posterior elements. Evidence of fusion was present in eight of 44 (18%) of patients. C2-C3 and C5-C6 were almost equally affected. Block fusions involving multiple vertebrae were seen. Analysis of sequential studies in 16 patients showed evidence of progression in five. These results reveal an incidence of fusions that is lower than reported previously. There is radiologic evidence from serial studies that the fusions are progressive, and because these patients are children, the fusion process may not be complete, which may account for the lower incidence of fusions than in previous studies. The pattern of fusions is different from that in earlier studies, which may be a result of the method of diagnosis because this population is less likely to include atypical forms of other syndromes (which have a higher incidence of cervical fusions, particularly at C2-C3). Regarding other congenital anomalies, it appears that butterfly vertebrae are especially prevalent in association with Crouzon syndrome.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1998
DOI: 10.1097/00006534-199808000-00027
Abstract: Monotopic phosphoglycosyl transferase enzymes (monoPGTs) initiate the assembly of prokaryotic glycoconjugates essential for bacterial survival and proliferation. MonoPGTs belong to an expansive superfamily with a erse and richly annotated sequence space however, the biochemical roles of most monoPGTs in glycoconjugate biosynthesis pathways remain elusive. To better understand these critical enzymes, we have implemented activity-based protein profiling (ABPP) probes as protein-centric, membrane protein compatible tools that lay the groundwork for understanding the activity and regulation of the monoPGT superfamily from a cellular proteome. With straightforward gel-based readouts, we demonstrate robust, covalent labeling at the active site of various representative monoPGTs from cell membrane fractions using 3-phenyl-2H-azirine probes.
Publisher: Wiley
Date: 28-02-2014
Abstract: The ability to drive safely can be affected by an acquired brain injury. Following acquired brain injury, clients may experience driving disruptions, formal assessment, return to driving or permanent cessation. Health professionals may be involved in formal driving or component skills' assessment and rehabilitation, or interventions for continued community participation. Meeting the needs of clients related to driving remains a challenging area of clinical practice. The aim of this study was to investigate how driving issues are currently managed by acquired brain injury rehabilitation teams. This study utilised a qualitative phenomenological approach to gain insight into the approaches undertaken by four rehabilitation teams working with clients post-acquired brain injury. Semi-structured, audiotaped interviews were conducted with 25 participants who had identified driving as part of their role. Health professional participants described three major areas of clinical focus, describing strategies and challenges associated with each. These were as follows: 'Integrating driving goals into rehabilitation' which involved optimising timing and acknowledging the clients' focus on driving while enhancing driving and rehabilitation outcomes 'Managing emotional responses' which required protecting therapeutic relationships and providing information, as well as responding to more extreme responses and finally 'Managing unlicensed driving and meeting long-term needs', which participants identified as the most challenging aspect. Strategies involved using set procedures, building on knowledge of the client, supporting the family and exploring alternatives. The teams described a range of strategies used to address the challenges related to driving and driving cessation which can be applied to successfully manage this issue in acquired brain injury rehabilitation.
Publisher: Springer Science and Business Media LLC
Date: 12-05-2020
DOI: 10.1186/S13018-020-01692-9
Abstract: Healing of tendons after injury involves the proliferation of tenocytes and the production of extracellular matrix however, their capacity to heal is limited by poor cell density and limited growth factor activity. Flightless I (Flii) has previously been identified as an important regulator of cellular proliferation and migration, and the purpose of this study was to evaluate the effect of differential Flii gene expression on tenocyte function in vitro. The role of Flii on tenocyte proliferation, migration, and contraction was assessed using established assays. Tenocytes from Flii +/− , wild-type, and Flii overexpressing mice were obtained and the effect of differential Flii expression on migration, proliferation, contraction, and collagen synthesis determined in vitro . Statistical differences were determined using unpaired Student’s t test and statistical outliers were identified using the Grubbs’ test. Flii overexpressing tenocytes showed significantly improved migration and proliferation as well as increased collagen I secretion. Explanted tendons from Flii overexpressing mice also showed significantly elevated tenocyte outgrowth compared to Flii +/− mice. In contrast to its role in dermal wound repair, Flii positively affects cellular processes in tendons. These findings suggest that Flii could be a novel target for modulating tenocyte activity and improving tendon repair. This could have significant clinical implications as novel therapeutic targets for improved healing of tendon injuries are urgently needed.
Publisher: Public Library of Science (PLoS)
Date: 08-09-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-1996
DOI: 10.1097/00006534-199603000-00036
Abstract: Because of the efficacy of tropomyosin receptor kinase (Trk) inhibitor therapy in tumours with rearrangements of the neurotrophic tyrosine kinase receptor genes (NRTK genes), there has been a surge in demand for NTRK fusion screening. To date, most studies involving mesenchymal tumours have focused on soft tissue tumours, and data on bone tumours are sparse. Hence, we aimed to explore the frequency of NTRK fusions in a large series of primary bone tumours. Immunohistochemical expression of pan-Trk was successfully assessed in 354 primary bone tumours by the use of tissue microarrays. In a selection of positive cases, additional molecular analysis for NTRK fusions was performed with anchored multiplex polymerase chain reaction-based targeted next-generation sequencing. Positivity was found in 19 cases (5%), which comprised Ewing sarcoma (n = 6, 33%), osteosarcoma (n = 11, 13%), and giant-cell tumour of bone (n = 2, 3%). In all except one case, cytoplasmic staining was observed. Weak staining was most often observed (n = 13), although five cases showed moderate staining and one case showed focal strong staining. Molecular analysis was successful in six cases, all of which were negative for NTRK fusions. The likelihood of finding an NTRK fusion in bone tumours in clinical practice is extremely low. This may imply that, if more comprehensive large-scale molecular studies confirm this, routine predictive NTRK testing in bone tumour patients with advanced disease may be reconsidered.
Publisher: Korean Cleft Palate-Craniofacial Association
Date: 20-04-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2005
DOI: 10.1097/00001665-200501000-00009
Abstract: The authors report nine patients with unicoronal synostosis who were treated with the same surgical protocol and who now have reached skeletal maturity. These patients all underwent surgery at the Australian Craniofacial Unit during a 2-year period by one of two craniofacial surgeons and one of two neurosurgeons. The operative procedure in all of these cases was the same technique, in which there was unilateral advancement of the affected side. No cases required reoperation however, one case subsequently required revision of the coronal scar, and two cases required strabismus correction. All cases were reviewed to evaluate patient results by the clinical staff recent photographs at skeletal maturity also were reviewed. Two patients had adult computed tomography scans available for skeletal assessment, and one additional patient had undergone serial computed tomography scans during childhood. The patients also completed an anonymous questionnaire to ascertain their assessment of their appearance. The results of the clinical and radiologic assessments and questionnaire suggest that the operative procedure undertaken in these cases has produced satisfactory results in the long term, with few in iduals requiring (or even considering) additional surgery, despite some persistent asymmetry.
Publisher: SAGE Publications
Date: 03-2006
DOI: 10.1597/04-174.1
Abstract: To investigate facial asymmetry associated with both deformational and synostotic plagiocephaly and to identify variables based on skeletal landmarks that distinguish the conditions and quantify severity. Retrospective, cross sectional. Australian Craniofacial Unit, Adelaide. Proportional differences between bilateral distances and principal component (PC) analysis of the skeletal landmarks. The three-dimensional positions of 78 osseous landmarks were determined from computed tomography (CT) scans of 21 patients with deformational plagiocephaly (DP), 20 patients with unilateral coronal synostosis (UCS), and 2 patients with unilateral lambdoid synostosis (ULS). For both DP and UCS, significant asymmetry was found for the orbital depths, mandibular lengths, maxillary depths, zygomatic arch lengths, lateral base of the parietal bone, and the angle between the anterior and the posterior cranial base projected onto the axial plane. The small s le size for ULS precluded definitive statistical statements but allowed some useful comparisons with the other conditions. The first three PC scores were able to distinguish among the three conditions and which side was affected. The asymmetry of the cranial base and facial structures, arising from localized abnormality or deformational forces in either the frontal or the occipital regions, can be quantified by a plethora of bilateral features or summarized by PC analysis.
Publisher: SAGE Publications
Date: 09-2005
DOI: 10.1597/04-142051R.1
Abstract: Goldenhar syndrome consists of the triad of craniofacial microsomia, occular dermoid cysts, and spinal anomalies. The exact nature of the spinal anomalies remains poorly defined in the existing craniofacial literature, possibly due to these anomalies being managed by orthopedic surgeons rather than by craniofacial surgeons. The aim of this study was to clarify the nature and extent of these spinal anomalies. Review of case notes of patients who had their diagnosis confirmed following review by a clinical geneticist and in conjunction with radiographs (supplemented by three-dimensional computed tomographic [CT] scans where available). Seven patients fulfilled the entry criteria and had material available for study. A wide range of anomalies was present, including butterfly vertebrae hemivertebrae, which produced secondary scoliosis kyphosis and rib anomalies. Anomalies occurred at all levels within the spine. The possibility of spinal anomalies at all levels of the spine should be considered by those treating cases of Goldenhar syndrome, because these anomalies cannot be predicted from the severity of the facial malformation.
Publisher: The Company of Biologists
Date: 2020
DOI: 10.1242/DEV.190488
Abstract: Craniofacial development is a complex morphogenic process that requires highly orchestrated interactions between multiple cell types. Blood vessel-derived angiocrine factors are known to promote proliferation of chondrocytes in Meckel's cartilage to drive jaw outgrowth, however the specific factors controlling this process remain unknown. Here, we use in vitro and ex vivo cell and tissue culture, as well as genetic mouse models to identify IGF-1 as a novel angiocrine factor directing Meckel's cartilage growth during embryonic development. We show that IGF-1 is secreted by blood vessels and that deficient IGF-1 signalling underlies mandibular hypoplasia in Wnt1-Cre Vegfafl/fl mice that exhibit vascular and associated jaw defects. Furthermore, conditional removal of IGF-1 from blood vessels causes craniofacial defects including a shortened mandible, and reduced proliferation of Meckel's cartilage chondrocytes. This demonstrates a critical angiocrine role for IGF-1 during craniofacial cartilage growth, and identifies IGF-1 as a putative therapeutic for jaw and/or cartilage growth disorders.
Publisher: Informa UK Limited
Date: 26-02-2018
DOI: 10.1080/09297049.2018.1441821
Abstract: Neurodevelopmental delays are known to occur in children with metopic synostosis, but it is presently unclear whether the cognitive, behavioral and psychological outcomes of children with metopic synostosis differ to those of their healthy peers. This meta-analysis consolidated data from 17 studies (published prior to August 2017) that examined the cognitive, behavioral and psychological outcomes of children (n = 666 aged ≤19 yrs) with metopic synostosis. Hedges'g (g
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.BJOMS.2015.06.007
Abstract: Our aim was to examine the relations between type and site of the fracture, age of the patient, and the management and outcomes, among children diagnosed with orbital fractures at the Women's and Children's Hospital, Adelaide, during a 10-year period from 1 January 2003 to 31 December 2012. The records of 41 children whose ages ranged from 8 months to 15 years were analysed. There was a male predominance (n=33). Two most common fractures were orbital floor and multiwalled fractures, with medial wall as the second most common site. The most common cause of injury was sport, more often with increasing age. In contrast, falls were more common among young children. Fractures of the orbital roof were more common among young children, all of ours being in children 10 years old or less. Lateral wall fractures were also more common among young children and declined in frequency with increasing age. In contrast, fractures of the orbital floor and medial wall can occur at any age, though those of the medial wall were more common among older children. As children grow their behaviour and activities change, and the mechanism by which they become injured also changes. Growth and development of the craniofacial skeleton lead to differences in the patterns of fractures with age. Fractures of the orbital roof and lateral wall are more common among young children, while those of the orbital floor and medial wall can occur at any age.
Publisher: SAGE Publications
Date: 07-2012
DOI: 10.1597/11-151
Abstract: It is clear that population-specific norms should be used when planning plastic and reconstructive surgery for selected patients. In this study, we aimed to generate nasal and labial reference values by applying a stereophotogrammetric technique. A further aim was to investigate the effect of sexual dimorphism, age-related changes, and the interrelation between nasal and labial morphology. Cross-sectional study. The data were collected from different locations on the Malaysian peninsula. A total of 276 Asian Malays (138 males and 138 females) were included in this study, and a three-dimensional system was used for capturing data. The s le was ided into three age groups: 13 to 14, 15 to 17, and 18 to 36 years. Twenty-five dimensions of the nose and lips were measured and analyzed separately in males and females. Significant differences between males and females were identified in 11 distances, and significant effects of age were found in most of the dimensions ( p .05). Significant correlations between the nasal and labial dimensions were recorded, particularly between lateral lip height and width of the ala insertion. A principal component analysis showed interrelationships between the nasal width distances and upper lip height. This study has provided a new three-dimensional database for nose and lip morphology in Malays and demonstrated patterns of variation that can be used by surgeons to make comparisons within and between different human populations and also to develop treatment plans for their patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2011
Publisher: Springer Science and Business Media LLC
Date: 10-08-2012
DOI: 10.1007/S00418-012-1011-7
Abstract: Craniosynostosis is a developmental disorder of the skull arising from premature bony fusion of cranial sutures, the sites of skull bone growth. In a recent gene microarray study, we demonstrated that retinol-binding protein 4 (RBP4) was the most highly downregulated gene in suture tissue during the pathological process of premature bony fusion. To gain insight into the function of RBP4 in cranial sutures, we analysed primary cells cultured from human cranial suture mesenchyme. These cells express RBP4 but not CRBP1, cellular retinol-binding protein 1, the typical cytoplasmic retinol storage protein. Using flow cytometry, we showed that suture mesenchymal cells express the RBP4 receptor, STRA6, on the cell surface. In a cell culture model of cranial osteogenesis, we found that RBP4 was significantly downregulated during mineralization, analogous to its decrease in pathological suture fusion. We found that cranial suture cells do not secrete detectable levels of RBP4, suggesting that it acts in a cell-autonomous manner. High-resolution confocal microscopy with a panel of antibody markers of cytoplasmic organelles demonstrated that RBP4 was present in several hundred cytoplasmic vesicles of about 300 nm in diameter which, in large part, were conspicuously distinct from the ER, the Golgi and endosomes of the endocytic pathway. We speculate that in suture mesenchymal cells, endogenous RBP4 receives retinol from STRA6 and the RBP4-retinol complex is stored in vesicles until needed for conversion to retinoic acid in the process of osteogenesis. This study extends the role of RBP4 beyond that of a serum transporter of retinol and implicates a broader role in osteogenesis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2020
Publisher: Wiley
Date: 23-05-2007
DOI: 10.1002/AOC.1231
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.OPHTHA.2004.12.037
Abstract: To document the frequency of ophthalmic sequelae in patients with Crouzon syndrome before the influence of craniofacial surgery. Retrospective observational case series. Seventy-one consecutive patients with a clinical diagnosis of Crouzon syndrome assessed before craniofacial or ophthalmic surgery at the Australian Craniofacial Unit between 1984 and 2000. Review of clinical records with documentation of patient age, gender, visual acuity, refractive error, diagnosis of amblyopia, squint, eye movement dysfunction, nystagmus, fundus examination, examination of the anterior segment, interpupillary distance, and intercanthal distance. The frequency of ophthalmic signs and visual impairment, defined as a visual acuity of 6/12 or less. Visual impairment in at least 1 eye occurred in 35% of patients and was bilateral in 9%. The most common cause of visual impairment was amblyopia, which was present in 21% of patients, followed by optic atrophy in 7%. Ametropia occurred in 77% of patients 57% had hypermetropia of > or =+2 diopters (D) and 20% had myopia of > or =-0.5 D. Strabismus occurred in 39% of patients. Although exposure keratopathy was observed in 15% of patients, this complication was well managed and caused no reduction in visual acuity. Early detection to reduce amblyopia by correction of refractive errors, timely treatment of strabismus, and patching should be a priority for ophthalmologists and a goal of the craniofacial teams managing patients with Crouzon syndrome. Optic atrophy remains an important cause of visual impairment in these patients before decompressive craniectomy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2009
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.IJPORL.2011.11.008
Abstract: The purpose of this study was to use three-dimensional computed tomography data and computer imaging technology to assess the skeletal components of the naso-pharyngeal area in patients with cleft lip and palate and to quantify anatomical variations. CT scans were obtained from 29 patients of Malay origin with cleft lip and palate aged between 0 and 12 months and 12 noncleft patients in the same age group, using a GE Lightspeed Plus Scanner housed in Hospital Universiti Sains Malaysia. Measurements were obtained using the 'Persona' three-dimensional software package, developed at Australian Craniofacial Unit, Adelaide. The results of the present study show that there is an increased nasopharyngeal space in cleft lip and palate that may lead to compression of the nasopharyngeal structures, including the Eustachian tube. Alterations of the medial pterygoid plate and the hamulus may lead to an alteration in the origin and orientation of the tensor veli palatini muscle leading to alteration in its function. These anatomical variations may compromise the dilatory mechanism of the Eustachian tube, thus leading to recurrent middle ear infections in cleft children and subsequent loss of hearing.
Publisher: Elsevier BV
Date: 04-2006
Publisher: Springer Science and Business Media LLC
Date: 03-02-1997
Abstract: To review the hand radiographs of patients with Crouzon syndrome, to look for extracranial manifestations of the condition at this site. The hand radiographs of those with Crouzon syndrome attending the Craniofacial Service at Great Ormond Street between 1985 and 1996 were reviewed. Thirty-three patients underwent a total of 34 radiographs, one patient having had a serial study. This revealed a range of minor anomalies. Most striking was the presence of carpal fusions in four cases, a feature which has not previously been reported. The hands of Crouzon syndrome may have anomalies including carpal fusions, and these results are evidence that the condition may produce subtle effects on the hands.
Publisher: Elsevier BV
Date: 02-2007
DOI: 10.1016/J.BJPS.2006.01.032
Abstract: With little in the published literature on the conservative management of facial fractures we set out to determine whether our current criteria for treatment are valid. Two hundred and thirty adult patients with fractures of the facial skeleton were treated conservatively by our unit between February 1997 and January 2003. Their notes were reviewed retrospectively. Most patients were males (76%), the average age was 38 years, and drugs or alcohol were a significant aspect of the history in 30% of the cases. The most common mechanism of injury was assault (47%), followed by falls and sporting injuries. Fifty percent of the fractures involved the orbital or orbito-zygomatic complex, and 55% had associated injuries. Average follow-up was for six weeks (range 0-44 weeks). Most patients were managed conservatively based on our current criteria of un-displaced/minimally displaced fracture (57%) or minimal/no symptoms (24%). At final review, a number had residual symptoms, but only three required corrective surgery. The other reasons for conservative management included patient non-compliance (11%), and medical contraindications (8%). Our results support current indications for the conservative management of facial fractures, but emphasise the need for ongoing follow-up of these patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2005
DOI: 10.1097/01.SAP.0000174355.56130.0A
Abstract: Opitz G BBB syndrome is a rare condition characterized by the 3 major anomalies of hypertelorism, cleft lip and palate, and hypospadias, although there may be other associated anomalies. The underlying genetic causes are complex and consist of both X-linked recessive and autosomal dominant forms of the disorder. Previously, there have been publications on the underlying genetics and case reports, but there have been few reports regarding the long-term outcome. The aim in this study was to review the range of clinical presentation and evaluate outcomes of the multidisciplinary management of a cohort of patients with Opitz G BBB syndrome. In a 25-year period, 7 patients with Opitz G BBB syndrome were managed by the Australian Craniofacial Unit (ACFU), 5 male and 2 female. Most of the patients are now reaching skeletal maturity. Each one presented with a range of severity in the triad of hypertelorism, cleft lip and palate, and hypospadias anomalies. The males all exhibited the triad of anomalies, while the females both had hypertelorism, only 1 had isolated cleft palate, and neither had any genitourinary anomalies. Each patient underwent multidisciplinary assessment to make a treatment plan for staged management of different anomalies. Plan for surgical corrections of facial anomalies were performed according to the unit's protocol management of both hypertelorism and cleft lip and palate, but the presence of these coexisting anomalies required adjustment of the standard protocol of management of cleft lip and palate. In conclusion, we recommend that patients with Opitz G BBB syndrome require careful evaluation, and management of the anomalies should be in a coordinated manner by a multidisciplinary team.
Publisher: Elsevier BV
Date: 07-1998
DOI: 10.1016/S0165-5876(98)00043-3
Abstract: Nasal dermoid cysts are congenital malformations which result from anomalous embryological development. Two cases occurring in siblings are presented. There have been several previous reports that the condition may be familial but in this report the initial suspicion of the milder anomaly in the younger child was raised primarily because of his older brother's history. This further report suggests that the incidence of familial occurrence of this anomaly may be greater than current literature suggests, and the possibility that other family members may be affected should be remembered by clinicians treating patients with this condition.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1998
DOI: 10.1097/00001665-199801000-00018
Abstract: Broad toes are the classic clinical finding occurring in the feet in Pfeiffer's syndrome patients, but few cases undergo formal radiological assessment. However, the feet in other craniosynostosis syndromes resulting from mutations of the fibroblast growth factor receptor 2 gene have anomalies at many other sites within the feet, which raised the possibility that there may also be a wider range of anomalies other than broad big toes in the feet of those with Pfeiffer's syndrome. The object of this study was to assess prospectively the incidence and pattern of clinical and radiographic anomalies of the feet of patients with a confirmed diagnosis of Pfeiffer's syndrome. Twenty-two Pfeiffer's syndrome patients were examined both clinically and radiologically for anomalies of the feet. Clinical examination revealed broad big toes in 12 patients and syndactyly in 2. Radiographs of the feet were evaluated by a radiologist with an interest in skeletal dysplasia as well as by members of the Craniofacial team. A wider range of radiological than clinical anomalies involving the phalanges, metatarsals, and tarsals was seen. The severity of the anomalies observed ranged from normal to those resembling the feet of Apert's syndrome patients. Only 4 patients had radiologically normal feet. These radiographic findings suggest that there is a range of foot anomalies more extensive than the broad big toes, which are classically associated with Pfeiffer's syndrome.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1997
DOI: 10.1097/00006534-199708000-00056
Abstract: Aiming at the problem of massive data storage and transaction authority in the blockchain system in the data sharing transaction scenario, this paper proposes a blockchain system for the controllable sharing transaction of massive data. By designing the blockchain system model of the consortium chain and private chain, reconstructing the data structure of the block, and introducing the InterPlanetary File System (IPFS) technology, we adopt the off-chain storage method to solve the problem of high cost caused by too much data carried by the block. The isolation control of data resource transactions is realized by introducing identity authentication and channel mechanism, which meets the needs of different subjects for confidentiality of transaction data information. From the analysis results of cold chain logistics efficiency, in the five years from 2017 to 2021, the comprehensive cold chain logistics efficiency, pure technology cold chain logistics efficiency, and scale cold chain logistics efficiency of agricultural product cold chain logistics in a certain region have all reached above 0.9. The return to scale remains unchanged, and the cold chain logistics resources have been effectively allocated and reasonably utilized. The value of comprehensive cold chain logistics efficiency, pure technology cold chain logistics efficiency, and scale cold chain logistics efficiency in a certain month is less than 1, which means that the cold chain logistics efficiency is weak or ineffective. This shows that in these years, the infrastructure investment, cold chain technical support, and management level related to the cold chain logistics of agricultural products in a certain region need to be strengthened, and it is necessary to adjust the input-output structure and allocate resources reasonably. From 2018 to 2021, the total factor productivity of agricultural product cold chain logistics in a certain region is greater than 0.85, indicating that the level of total factor productivity is relatively high during this time period, and the increase in the efficiency of technical cold chain logistics is the main reason for the increase in total factor productivity.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2006
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.JAAPOS.2016.04.007
Abstract: Pfeiffer syndrome is a rare, genetic condition characterized by craniosynostosis and midface hypoplasia, with resultant ophthalmic sequelae. The gold standard of treatment is fronto-orbital advancement. We analyzed a large database of Pfeiffer syndrome patients to report the rate of ophthalmic sequelae and the long-term visual outcomes after craniofacial surgery and to compare Pfeiffer syndrome to other craniosynostosis syndromes. The medical records of Pfeiffer syndrome patients examined between 1988 and 2010 were examined retrospectively. Diagnosis was based on clinical and genetic testing. Long-term data were presented as a rate of incidence per person-year to overcome variable follow-up times. A total of 22 patients were included. Proptosis (n = 21 [95%]), refractive error (n = 13 [59%]), and strabismus (n = 12 [55%]) were the most common primary features at presentation. Exposure keratitis (n = 9 [41%]) and amblyopia (n = 3 [14%]) were the most common secondary features. At presentation, 24 eyes [86%] with documented best-corrected visual acuity were normal 4 [14%] were impaired and none were blind. Fronto-orbital advancement reduced the rate of proptosis from 28% erson-year at presentation to 2% erson-year. There were no cases of active exposure disease postoperatively. At last follow-up, there was a 7% erson-year rate of impaired vision secondary to corneal scarring and amblyopia and a 3% erson-year rate of blindness-all from optic atrophy. In this study, the rates of proptosis and exposure keratitis were high in Pfeiffer syndrome, especially compared to Apert and Crouzon syndromes. Fronto-orbital advancement was successful in correcting orbital abnormalities. Long-term ophthalmic follow-up is essential to ensure best visual outcome.
Publisher: Elsevier BV
Date: 09-2004
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2013
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.BONE.2013.04.013
Abstract: From birth, the vault of the skull grows at a prodigious rate, driven by the activity of osteoblastic cells at the fibrous joints (sutures) that separate the bony calvarial plates. One in 2500 children is born with a medical condition known as craniosynostosis because of premature bony fusion of the calvarial plates and a cessation of bone growth at the sutures. Bone morphogenetic proteins (BMPs) are potent growth factors that promote bone formation. Previously, we found that Glypican-1 (GPC1) and Glypican-3 (GPC3) are expressed in cranial sutures and are decreased during premature suture fusion in children. Although glypicans are known to regulate BMP signalling, a mechanistic link between GPC1, GPC3 and BMPs and osteogenesis has not yet been investigated. We now report that human primary suture mesenchymal cells coexpress GPC1 and GPC3 on the cell surface and release them into the media. We show that they inhibit BMP2, BMP4 and BMP7 activities, which both physically interact with BMP2 and that immunoblockade of endogenous GPC1 and GPC3 potentiates BMP2 activity. In contrast, increased levels of GPC1 and GPC3 as a result of overexpression or the addition of recombinant protein, inhibit BMP2 signalling and BMP2-mediated osteogenesis. We demonstrate that BMP signalling in suture mesenchymal cells is mediated by both SMAD-dependent and SMAD-independent pathways and that GPC1 and GPC3 inhibit both pathways. GPC3 inhibition of BMP2 activity is independent of attachment of the glypican on the cell surface and post-translational glycanation, and thus appears to be mediated by the core glypican protein. The discovery that GPC1 and GPC3 regulate BMP2-mediated osteogenesis, and that inhibition of endogenous GPC1 and GPC3 potentiates BMP2 responsiveness of human suture mesenchymal cells, indicates how downregulation of glypican expression could lead to the bony suture fusion that characterizes craniosynostosis.
Publisher: SAGE Publications
Date: 09-2006
DOI: 10.1597/05-023
Abstract: To investigate anatomical variations and abnormalities of cervical spine morphology in unoperated infants with cleft lip and palate. Retrospective cross-sectional investigation of infants born with nonsyndromic cleft lip and palate using computed tomography scans acquired for investigation of a spectrum of clinical conditions. Computed tomography scan data were obtained from 29 unoperated cleft lip and palate infants and 12 noncleft infants of Malay origin, ages 0 to 12 months. Observational study of cervical spine computed tomography scans. Heights of cervical vertebral bodies (C2-C7) and intervertebral spaces were measured from landmarks identified from computed tomography reformats and three-dimensional computed tomography reconstructions. Linear modeling of heights and spaces, with age as a covariate, was undertaken to identify differences between the s les. Anomalous features observed in the cleft lip and palate s le included short posterior arch of C1 (2/29), abnormal development of the anterior arch of C1 (2/29), and fusions of the posterior arch of C2 and C3 (2/29). No anomalies of the cervical spine were observed in the noncleft s le. Although the heights of three cervical vertebral bodies were significantly smaller and two intervertebral spaces were significantly larger in infants with cleft lip and palate compared with noncleft infants (p .05), overall length of the cervical spine did not differ significantly between the s les. There was evidence for subtle upper spinal anomalies in the infant cleft lip and palate population. Our finding of reduced size of some cervical vertebral bodies may reflect delayed upper spinal development in infants with cleft lip and palate.
Publisher: Wiley
Date: 14-02-2017
DOI: 10.1111/ADJ.12443
Abstract: The aim of this study was to determine the prevalence of dental anomalies within an Australian paediatric population using panoramic radiographs. This was a prospective review of 1050 panoramic radiographs obtained as part of a school dental screening program in suburban and rural New South Wales, Australia. Fifty-four (5.14%) patients had a dental anomaly present. Agenesis was noted to have occurred 69 times across 45 patients (4.28%), along with seven cases of impaction (0.6%) and three cases of supernumerary teeth (0.28%). Dental anomalies rarely occur in the Australian population, which possesses a wide-ranging multiethnic cohort. Despite their rarity, they can be incidentally discovered so identification and management by dental practitioners are important.
Publisher: Wiley
Date: 11-1999
Publisher: Wiley
Date: 03-2010
DOI: 10.1111/J.1834-7819.2009.01178.X
Abstract: Van der Woude syndrome (VWS) is the most common clefting syndrome in humans. It is characterized by the association of congenital lower lip fistulae with cleft lip and/or cleft palate. VWS in iduals have a high prevalence of hypodontia. Although caused by a single gene mutation, VWS has variable phenotypic expression. This study aimed to describe the range of clinical presentations in 22 in iduals with VWS to facilitate its diagnosis. A retrospective study of 22 patients with a diagnosis of VWS was undertaken at the Australian Craniofacial Unit (ACFU) in Adelaide. Three extended families with affected members were included in the study cohort. The overall prevalence of lip pits in this study cohort was 86%. Cleft phenotypes included bilateral cleft lip and palate (32%) unilateral cleft lip and palate (32%) submucous cleft palate (23%) and isolated cleft hard and soft palate (9%). Missing permanent teeth were reported in 86% of affected in iduals. Submucous cleft palate in VWS may go undiagnosed if the lower lip pits are not detected. Associated hypodontia and resultant malocclusions will also require management by a dental team.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.BONE.2016.09.019
Abstract: The TWIST-1 gene encodes a basic helix-loop-helix (bHLH) transcription factor important in mediating skeletal and head mesodermal tissue development. Bone marrow-derived mesenchymal stem/stromal cells (BMSC), express high levels of TWIST-1, which is down regulated during ex vivo expansion. Cultured BMSC over-expressing TWIST-1 display decreased capacity for osteogenic differentiation and an enhanced capacity to undergo adipogenesis, suggesting that TWIST-1 is a mediator of lineage commitment. However, little is known regarding the mechanism(s) by which TWIST-1 mediates cell fate determination. In this study, microarray analysis was used to identify a novel downstream TWIST-1 target, tyrosine kinase receptor c-ros-oncogene 1 (C-ROS-1), which was down regulated in TWIST-1 over-expressing BMSC. Chromatin immunoprecipitation analysis showed that TWIST-1 directly bound to two E-box binding sites on the proximal C-ROS-1 promoter. Knock-down of C-ROS-1 in human BMSC and cranial bone cells resulted in a decreased capacity for osteogenic differentiation in vitro. Conversely, suppression of C-ROS-1 in BMSC resulted in an enhanced capacity to undergo adipogenesis. Furthermore, reduced C-ROS-1 levels led to activation of different components of the PI3K/AKT/mTORC1 signalling pathway during osteogenic and adipogenic differentiation. Collectively, these data suggest that C-ROS-1 is involved in BMSC fate switching between osteogenesis and adipogenesis, mediated via PI3K/AKT/mTORC1 signalling.
Publisher: Elsevier BV
Date: 12-2003
DOI: 10.1016/S1010-5182(03)00067-2
Abstract: Teratomas are exceptionally rare malformations in the head and neck region. They are mostly benign but as a direct result of their rarity, most clinician's experience of these tumours is very limited, and consequently most of the associated literature consists of single case reports. In this paper, however, all the cases managed by a major Craniofacial Unit (the Australian Craniofacial Unit) were reviewed to attempt to identify common problems encountered in their management. All cases managed by the Australian Craniofacial Unit over the last 25 years were reviewed. In total a series of nine cases was identified, but two were seen and operated on in overseas centres and the data in these cases were incomplete, and have been excluded from the study. Case note, radiology and pathology review was undertaken to collect data. In total a series of seven cases was identified as suitable for inclusion in this study. Six of these have had a minimum of 9 years follow-up, three having completed growth. The initial and subsequent management demonstrates that these tumours when benign can be successfully removed, but depending on the affected site may require continued multidisciplinary management until growth has finished.
Publisher: Springer Science and Business Media LLC
Date: 12-2007
Abstract: Craniosynostosis, the premature fusion of calvarial sutures, is a common craniofacial abnormality. Causative mutations in more than 10 genes have been identified, involving fibroblast growth factor, transforming growth factor beta, and Eph/ephrin signalling pathways. Mutations affect each human calvarial suture (coronal, sagittal, metopic, and lambdoid) differently, suggesting different gene expression patterns exist in each human suture. To better understand the molecular control of human suture morphogenesis we used microarray analysis to identify genes differentially expressed during suture fusion in children with craniosynostosis. Expression differences were also analysed between each unfused suture type, between sutures from syndromic and non-syndromic craniosynostosis patients, and between unfused sutures from in iduals with and without craniosynostosis. We identified genes with increased expression in unfused sutures compared to fusing/fused sutures that may be pivotal to the maintenance of suture patency or in controlling early osteoblast differentiation (i.e. RBP4 , GPC3 , C1QTNF3 , IL11RA , PTN , POSTN ). In addition, we have identified genes with increased expression in fusing/fused suture tissue that we suggest could have a role in premature suture fusion (i.e. WIF1 , ANXA3 , CYFIP2 ). Proteins of two of these genes, glypican 3 and retinol binding protein 4, were investigated by immunohistochemistry and localised to the suture mesenchyme and osteogenic fronts of developing human calvaria, respectively, suggesting novel roles for these proteins in the maintenance of suture patency or in controlling early osteoblast differentiation. We show that there is limited difference in whole genome expression between sutures isolated from patients with syndromic and non-syndromic craniosynostosis and confirmed this by quantitative RT-PCR. Furthermore, distinct expression profiles for each unfused suture type were noted, with the metopic suture being most disparate. Finally, although calvarial bones are generally thought to grow without a cartilage precursor, we show histologically and by identification of cartilage-specific gene expression that cartilage may be involved in the morphogenesis of lambdoid and posterior sagittal sutures. This study has provided further insight into the complex signalling network which controls human calvarial suture morphogenesis and craniosynostosis. Identified genes are candidates for targeted therapeutic development and to screen for craniosynostosis-causing mutations.
Publisher: Wiley
Date: 12-2005
Publisher: Mary Ann Liebert Inc
Date: 07-2020
Publisher: SAGE Publications
Date: 07-2014
DOI: 10.1597/12-252
Abstract: The rare craniofacial clefts form an important component of craniofacial pathology, but little has been written regarding the definitive management of affected patients. This report describes the presentation, management, and outcomes in a group of patients who have completed their protocol management for treatment of midline Tessier 0–14 clefts. A retrospective review of the clinical, photographic, and radiographic records of all midline cleft patients treated at a single center was performed. Data describing each patient's presenting features, surgical management, and final outcomes are presented. Four patients were identified as having completed protocol management for Tessier 0–14 midline clefting at the unit. The age range at the most recent follow-up was 19.3 to 36.3 years. Three patients had entered protocol management during infancy, and the remaining patient presented to the unit at 13.8 years of age. The surgical management regimen is described in detail. Outcomes for development, hearing, speech, and vision at maturity were all acceptable. Three patients attained a respectable educational and social status. With respect to facial aesthetics scores, the only significant difference after management was a significant worsening of deformity in the region of the orbits. The Whitaker grade for repeat surgery improved after management (3.25 before to 2.63 postmanagement), but this improvement was not statistically significant. Presented are the results of the first cohort of midline Tessier 0–14 cleft patients to have completed protocol management at a single craniofacial unit. As more patients complete their management in the future, further refinements to the protocol could be made.
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1111/J.1432-0436.2007.00244.X
Abstract: Craniosynostosis is the premature fusion of calvarial sutures. It results from abnormal differentiation or proliferation of cells within the osteogenic fronts of growing calvarial bones. To date, research has focused on animal models and in vitro organ and tissue culture to determine the molecular mechanisms controlling calvarial suture morphogenesis. Here, we test a new, in vivo-in vitro approach based on the hypothesis that calvarial suture cells passaged in minimal medium exhibit a stable gene expression profile similar to undifferentiated osteoblastic cells that can provide a benchmark for comparison with in vivo expression of differentiated tissue. We show that tissue-specific expression is lost after the first passage and, using cDNA microarrays, compare expression between fused suture tissue from craniosynostosis patients and in vitro de-differentiated explant cells. A large number of differentially expressed genes were identified, including novel genes WIF1, LEF1, SATB2, RARRES1, DEFA1, DMP1, PTPRZ1, and PTPRC, as well as those commonly associated with human suture morphogenesis, e.g., FGF2, MSX2, and BMP2. Two differentially expressed genes, WIF1 and FGF2, were further examined in an in vivo-in vivo comparison between unfused and prematurely fused tissue. The same pattern of differential expression was observed in each case, further validating the ability of our in vivo-in vitro approach to identify genes involved in in vivo human calvarial tissue differentiation.
Publisher: SAGE Publications
Date: 1997
DOI: 10.1597/1545-1569_1997_034_0079_TCSISC_2.3.CO_2
Abstract: Twenty patients with a diagnosis of Saethre-Chotzen syndrome had their cervical spine radiographs reviewed. Radiologic abnormalities including vertebral fusion were present in 9 of the 20 patients. Fusion of both the vertebra! bodies and the posterior elements was noted, although the latter site was more common. C2–3 was the level most commonly involved, although other levels were recorded. Analysis of sequential radiographs in nine patients revealed evidence of progression In seven patients. In those studies in children aged under 2 years, only 1 of 18 films showed evidence of fusion, while in those over 2 years of age, 10 of 12 showed evidence of fusion. These results reveal that the incidence of cervical anomalies in Saethre-Chotzen syndrome is greater than that in the general population. There is both direct and indirect evidence that the vertebral fusions are progressive during childhood.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2014
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.COLSURFB.2016.11.019
Abstract: Titania nanotubes (TNTs) engineered on titanium (Ti) surfaces (i.e. TNT/Ti) and loaded with specific drugs have been recognised as a promising solution for localised therapeutic delivery to address several medical problems not feasible with conventional drug administration. We propose the use of TNT/Ti protein-releasing implants to treat paediatric craniofacial abnormality in craniosynostosis caused by premature fusion of cranial sutures. In this study, we have analysed the biological response of human suture mesenchymal cells (SMCs), extracted from two different patients undergoing craniofacial reconstruction surgery, at the TNT/Ti implant surface. The experimental groups included large-diameter TNT/Ti implants, with and without biopolymer surface coating (Chitosan and Pluronic-F127) while the controls comprised of flat Ti disc and tissue culture plastic. The non-loaded implant surfaces and the cellular interactions at the implant-cell interface were characterised using scanning electron microscopy (SEM). The SMC adhesion, viability and proliferation were determined by MTT assay and manual cell counting at day 1 and day 3 of cell incubation. SEM showed significant reduction in initial attachment and adhesion of SMCs at TNT-cell biointerface compared with the control Ti discs. Subsequent cell proliferation results also revealed a decrease in the number of viable cells on the TNT surfaces. The nanotopography and structural features along with the surface chemistry dictated the cellular response, with nanotubular surfaces (with and without polymer coating) impeding cell adhesion and proliferation. Our findings hold promise for the use of TNT-based cranial implants as a delivery system to prevent sutural bone growth for advanced craniosynostosis therapy.
Publisher: The Electrochemical Society
Date: 2009
DOI: 10.1149/1.3232246
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2004
DOI: 10.1097/00001665-200411000-00024
Abstract: The authors report 32 patients with nonsyndromic isolated metopic synostosis who have undergone evaluation of their intracranial volumes. Twenty-five were male and seven were female. The measured intracranial volumes were compared with normal age-corrected values established in the authors' unit, and any differences were noted. The authors found that, although there was a range of intracranial volumes, in the male patients, intracranial volumes were significantly smaller than those found in the normal population (P < 0.05). However, this result was not found in the smaller female s le. These results contrast with those of smaller earlier studies, but the authors conclude that intracranial volumes are smaller than average for age-corrected normal values this finding highlights the need for volume expansion in conjunction with cranial reshaping.
Publisher: Wiley
Date: 20-04-2017
DOI: 10.1111/OCR.12170
Abstract: Glypican 1 (GPC1) and glypican 3 (GPC3) are bone co-regulators that act downstream in many of the signalling pathways associated with craniosynostosis. Morphometric data from GPC-knockout mice were analysed to determine whether elimination of GPC1 and GPC3 genes would alter mandibular morphology. The murine model included five male and five female mandibles in each of GPC1-knockout, GPC1/GPC3-knockout and wild-type (control) groups. Female GPC3-knockout mice had a very high rate of perinatal lethality, and therefore, only five males were included in this group. The mandibular morphology of GPC1-knockout (n=10), GPC3-knockout (n=5), GPC1/GPC3-knockout (n=10) and wild-type (n=10) mice was compared by analysing five landmark-based linear dimensions: anterior and posterior lengths, as well as ascending, descending and posterior heights. Measurements were recorded on three-dimensional micro-CT reconstructions. GPC3-knockout mandibles were larger than wild-type mandibles for all dimensions (P GPC1/GPC3-knockout>GPC1-knockout=wild-type) (P<.05) indicated that an increase in mandibular size was associated with increased GPC3 expression, but not GPC1. Alterations in GPC3 expression are likely to mediate changes to mandibular size in craniosynostosis. These findings have potential future applications in the prevention and treatment of craniosynostosis and associated craniofacial dysmorphology.
Publisher: SAGE Publications
Date: 09-1996
DOI: 10.1597/1545-1569_1996_033_0436_DFIPOC_2.3.CO_2
Abstract: The incidence of dental abnormalities in the cleft lip and palate population has been reported to be much higher than in the normal population. The role of genes in the production of a cleft lip and palate, and dental anomalies is thought to be complex, with autosomal dominant, recessive, and x-linked genes all playing a role. Noncleft parents can carry some of the cleft lip and palate genes, which produce clinically subtle manifestations in their facial skeleton. The purpose of this study was to look for evidence of increased dental anomalies in the non-cleft parents of cleft lip and palate children. The dentitions of the parents of 60 children with different types of cleft lip and palate were examined prospectively to see whether or not they exhibited features found more readily in the cleft lip and palate rather than did the normal population. Their dentitions were studied to record the following dental features: congenitally missing teeth, supernumerary teeth, or morphologic changes of the crowns of the permanent teeth. The number and position of any frenal attachments were also recorded. The results of this study did not show any differences in incidence of dental anomalies from the noncleft population. There was no evidence to support the hypothesis that congenital absence of lateral incisors is a microform of cleft lip and palate. Further, these results also failed to reveal any consistent pattern in the number and position of frenal attachments.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2015
DOI: 10.11124/JBISRIR-2015-2470
Abstract: Craniosynostosis is a condition characterized by the premature closure of one or more of the cranial vault sutures. It can occur alone or in association with other congenital defects and may be part of a syndrome. The sagittal suture is most commonly affected, comprising 40-60% of cases. Premature fusion of the sagittal suture can cause scaphocephaly due to compensatory anterior-posterior growth of the skull. This is morphologically considered as a narrow elongated skull with a decreased cephalic index, and is diagnosed clinically and/or radiologically. Both the indications for surgery and the techniques used have varied with time and location. Surgical techniques have evolved, from limited craniectomy to calvarial remodeling. In recent times a return to craniectomy methods has occurred with the more recent introduction of endoscopic methods. The objectives of this review were to identify and synthesize the best available evidence on the morphological, functional and neurological outcomes of craniectomy compared to cranial vault remodeling. This review considered studies of infants with primary isolated sagittal synostosis operated on or before the mean age of 24 months. The intervention of interest was local craniectomy and this was compared to cranial vault remodeling. Morphological (primary), functional and neurological (secondary) outcomes were included. Mortality, complications and aesthetic outcome were included as tertiary outcomes. A comprehensive search was undertaken across major databases. The retrieved studies were assessed by two independent reviewers for methodological validity prior to inclusion. Data was then extracted and, where possible, pooled in statistical meta-analysis. For descriptive studies, where statistical pooling was not possible, the findings are presented in narrative form. Search and retrieval: Based on critical appraisal, 27 studies were considered to be suitable for this review. These studies were all descriptive in nature. Meta-analysis was only possible for the primary morphological outcome (post-operative cephalic index).Morphological (cephalic index):At one year follow-up, post-operatively remodeling offers an advantage over craniectomy (Z = 4.16, P<0.0001)Morphological:Improvements of the cephalic index to varying degrees were seen in patients receiving either procedure and there is not enough evidence to suggest that either treatment group had greater improvement over the other.Functional and neurological:Although their global scores may be comparable to an age-matched population, patients with sagittal synostosis who have undergone a surgical repair of any type may have discrepancies in specific domains and may be at risk of developing learning disorders. There is insufficient primary research with inter-procedure comparisons of preoperative and postoperative cognitive and neurological outcomes.Tertiary outcomes:There is not enough evidence to comment on mortality or postoperative infection in either treatment group. Patients undergoing cranial vault remodeling have a higher rate of transfusion compared to those undergoing craniectomy however, it is likely that this difference relates to elective transfusion based on hospital-specific protocols. It remains unknown whether there is an inherently higher need for transfusion in patients undergoing remodeling procedures. Delaying surgery however may increase the risk of raised intracranial pressure (ICP) and its associated complications. Whilst there is no evidence for raised ICP post-craniectomy, a few studies have shown raised ICP in patients post-remodeling. There is not enough evidence to establish a relationship between both procedures and raised ICP. Aesthetic outcome appears to be "better" in patients who undergo remodeling however, there is little rigorous evidence to support this hypothesis. Conclusions were drawn from both the meta-analysis and the narrative results.When comparing the mean change in cephalic index one year after surgery, remodeling was shown to be superior to limited craniectomy in patients with isolated synostosis of the sagittal suture. However both procedures were seen to give improvements at short, medium and longer term time points. Improvements in cephalic index may be sustained, deteriorate or improve over time based on the current data neither procedure offers a clear long-term advantage over the other. Longer follow-up is required to compare outcomes at different time points.Patients who have surgery (any type) for isolated sagittal synostosis may have deficiencies in different subdomains at later school-age testing, whilst maintaining an age-appropriate global intelligence quotient (IQ) and school performance. There is no evidence to suggest that surgery of either type imparts any benefit in terms of functional or neurological outcomes.There is no evidence to suggest that surgery of either type imparts any benefit in terms of functional or neurological outcomes. While school performance and general IQ may be comparable to age-matched controls, patients with sagittal synostosis who have undergone surgical repair of any type may be at risk of deficiencies in sub-areas of testing and be at risk of learning disorders.There is insufficient evidence regarding mortality, infection, postoperative ICP and aesthetic outcome. While transfusion rates were greater in the remodeling group, this may be due to higher rates of elective transfusion.The inconclusive findings indicate an ongoing need for higher quality primary research comparing the morphological and functional outcomes of craniectomy and cranial vault remodeling in primary sagittal synostosis. Outcomes should be measured in both the short and long term.
Publisher: Wiley
Date: 19-09-2009
DOI: 10.1002/JCP.21586
Abstract: Osteogenic supplements are a requirement for osteoblastic cell differentiation during in vitro culture of human calvarial suture-derived cell populations. We investigated the ability of ascorbic acid and beta-glycerophosphate with and without the addition of dexamethasone to stimulate in vivo-like osteoblastic differentiation. Cells were isolated from unfused and prematurely fused suture tissue from patients with syndromic and non-syndromic craniosynostosis and cultured in each osteogenic medium for varying lengths of time. The effect of media supplementation was investigated with respect to the ability of cells to form mineralised bone nodules and the expression of five osteodifferentiation marker genes (COL1A1, ALP, BSP, OC and RUNX2), and five genes that are differentially expressed during human premature suture fusion (GPC3, RBP4, C1QTNF3, WIF1 and FGF2). Cells from unfused sutures responded more slowly to osteogenic media but formed comparable bone nodules to fused suture-derived cells after 16 days of culture in either osteogenic media. However, gene expression differed between unfused and fused suture-derived cells, as did expression in each osteogenic medium. When compared to expression in the explant tissue of origin, neither medium induced a level or profile of gene expression similar to that seen in vivo. Overall, our results demonstrate that cells from the same suture that are isolated during different stages of morphogenesis in vivo, despite being de-differentiated to a similar level in vitro, respond uniquely and differently to each osteogenic medium. Further, we suggest that neither cell culture medium recapitulates differentiation via activation of the same genetic cascades as occurs in vivo.
Publisher: Elsevier BV
Date: 11-1997
DOI: 10.1016/S0020-1383(97)82147-X
Abstract: Obesity represents a medical challenge for modern therapists. The main difficulty is that once obesity is established, it is hard to reverse. It is believed that once an increased body weight/adiposity content is reached it becomes the "reference" that energy mechanisms adjust towards keeping. Thus, following a weight loss, such as following liposuction/bariatric surgery, the metabolic balance would target this "reference" that represents the previously reached body weight/adiposity content. On the other hand, medical procedures of liposuction and bariatric surgery reduce the level of the adipocytes-produced hormone leptin. This leptin level reduction leads to an increase in food intake and a decrease in energy expenditure. Therefore, the reduced leptin would be among the signals received by the brain to trigger weight regain via processes aiming to re-establish the pre-liposuction re-bariatric surgery body weight or adiposity content. We suggest administering leptin so that the brain does not detect the post- liposuction ost-bariatric surgery weight loss thus, limiting the signals toward weight regain, leading to a better weight control.
Publisher: Springer Science and Business Media LLC
Date: 30-01-2009
DOI: 10.1038/EYE.2009.6
Abstract: To present the clinical features and management outcomes in a large longitudinal series of patients with craniofacial fibrous dysplasia (CFD). Retrospective interventional consecutive case series. Main outcome measures included signs and symptoms, radiographic findings, long-term outcomes, and postoperative complications. A total of 42 patients with CFD were identified. The mean age at presentation was 16.7 years mean follow-up was 12.6 years. Out of these 42 patients, 37 (88.1%) had unilateral involvement and 5 (11.9%) had bilateral involvement, of which 3 (7.1%) had McCune-Albright syndrome. The commonest presenting symptom was facial asymmetry (36 cases, 86%). The frontal bone was the most commonly involved (27 cases, 64.3%), zfollowed by the sphenoid (24 cases, 57.1%). The most common pattern of bone involvement was monostotic (32 cases, 76.2%). Radiological optic canal involvement occurred in 18 eyes of 15 (37.5%) patients, with optic atrophy in 9 eyes (18.8%) of 7 patients (16.7%). Surgical intervention was performed in 30 (71.4%) cases for both functional and reconstructive reasons. Optic canal decompression was performed in three cases, in all of which stabilization of vision was achieved no patient lost vision as a result of surgery. In this large longitudinal series of CFD, visual loss was not uncommon and occurred insidiously. The presenting clinical and radiological features, surgical interventions, and outcomes are discussed.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2006
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2009
Publisher: S. Karger AG
Date: 2004
DOI: 10.1159/000081933
Abstract: i Objective: /i Apert syndrome is caused by a mutation of the fibroblastic growth factor type 2 gene and in nearly all of the cases where the mutation has been identified it occurs in one of two adjacent sites of the gene, either position 252 or position 253. There is currently uncertainty whether a worse neurosurgical outcome occurs in association with a particular genotype. We investigated whether there were clinically subtle (but relevant) morphological differences in the craniofacial skeleton, which would result in differences in the intracranial volume, which might account for apparent differences in surgical outcome. i Method: /i Three-dimensional CT scans of pre-operative Apert syndrome whose genotype had been identified had the intracranial volume measured using the Cavalieri estimator with correction for partial voluming effects. The values were compared to age and sex normals and then the two genotypes compared. i Results: /i Intracranial volumes were measured for 22 cases, 16 with the 252 mutation and 6 with the 253 mutation. i Conclusions: /i All cases except two had greater than their sex- and age-adjusted mean normal intracranial volumes. For the 252 and 253 genotypes there were no discernible differences in intracranial volumes between the two genotypes.
Publisher: Springer Science and Business Media LLC
Date: 08-05-2012
Abstract: RT-qPCR is a common tool for quantification of gene expression, but its accuracy is dependent on the choice and stability (steady state expression levels) of the reference gene/s used for normalization. To date, in the bone field, there have been few studies to determine the most stable reference genes and, usually, RT-qPCR data is normalised to non-validated reference genes, most commonly GAPDH, ACTB and 18 S rRNA. Here we draw attention to the potential deleterious impact of using classical reference genes to normalise expression data for bone studies without prior validation of their stability. Using the geNorm and Normfinder programs, panels of mouse and human genes were assessed for their stability under three different experimental conditions: 1) disease progression of Crouzon syndrome (craniosynostosis) in a mouse model, 2) proliferative culture of cranial suture cells isolated from craniosynostosis patients and 3) osteogenesis of a mouse bone marrow stromal cell line. We demonstrate that classical reference genes are not always the most ‘stable’ genes and that gene ‘stability’ is highly dependent on experimental conditions. Selected stable genes, in idually or in combination, were then used to normalise osteocalcin and alkaline phosphatase gene expression data during cranial suture fusion in the craniosynostosis mouse model and strategies compared. Strikingly, the expression trends of alkaline phosphatase and osteocalcin varied significantly when normalised to the least stable, the most stable or the three most stable genes. To minimise errors in evaluating gene expression levels, analysis of a reference panel and subsequent normalization to several stable genes is strongly recommended over normalization to a single gene. In particular, we conclude that use of single, non-validated “housekeeping” genes such as GAPDH , ACTB and 18 S rRNA , currently a widespread practice by researchers in the bone field, is likely to produce data of questionable reliability when changes are 2 fold or less, and such data should be interpreted with due caution.
Publisher: Springer Science and Business Media LLC
Date: 06-12-2012
DOI: 10.1007/S00418-012-1062-9
Abstract: Retinol-binding protein 4 (Rbp4) is the major carrier of retinol in the bloodstream, a retinoid whose metabolites influence osteogenesis, chondrogenesis and adipogenesis. Rbp4 is mainly produced in the liver where it mobilizes hepatic retinol stores to supply other tissues. However, Rbp4 is also expressed in several extrahepatic tissues, including limbs, where its role is largely unknown. This study aimed to identify the cellular localization of Rbp4 to gain insight into its involvement in limb development and bone growth. Using immunohistochemistry, we discovered that Rbp4 was present in a variety of locations in developing embryonic and postnatal mouse hindlimbs. Rbp4 was present in a restricted population of epiphyseal chondrocytes and perichondral cells correlating to the future region of secondary ossification. With the onset of secondary ossification, Rbp4 was detected in chondrocytes of the resting zone and in chondrocytes that bordered invading cartilage canals and the expanding front of ossification. Rbp4 was less abundant in proliferating chondrocytes involved in primary ossification. Our data implicate the involvement of chondrocytic Rbp4 in bone growth, particularly in the formation of the secondary ossification center of the limb.
Publisher: Wiley
Date: 13-09-2013
DOI: 10.1111/CEO.12179
Abstract: The study aimed to review the presentation and long-term visual outcomes of patients with orbitotemporal neurofibromatosis. Retrospective case series. Patients with orbitotemporal neurofibromatosis presenting from 1981 to 2009. Demographic data, examination findings, causes of vision impairment and interventions performed were recorded for each patient from presentation through subsequent follow-up encounters. Visual impairment was defined as an ipsilateral Snellen acuity of <6/12. The proportion of patients with visual impairment or enucleation, the rate of new vision loss during follow up and causes for vision loss or enucleation. Thirty-seven patients (17 female) were included. Median presenting age was 15 years (range 2-45) with an average follow up of 7.4 years (range 0.5-20.3). Visual impairment occurred in 54% of patients at presentation. Causes were amblyopia (13 of 37), optic atrophy (4 of 37), previous enucleation/evisceration (2 of 37), and optic nerve glioma (1 of 37). At presentation, 76% of patients had ptosis, and 51% had strabismus. Thirty-one patients had surgery, with an average of two procedures per patient. At final follow up, 62% had visual impairment. The rate of visual decline was 2% per patient-years. Causes of visual decline were two patients with optic nerve atrophy, one with exposure keratitis and one whose cause was unknown. Five blind patients had enucleation. The first series of orbitotemporal neurofibromatosis to focus on visual outcomes was presented. Vision loss is common, with a high prevalence of amblyopia. Close monitoring from an early age is needed to prevent visual impairment.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2004
DOI: 10.1097/00001665-200401000-00015
Abstract: Mandibular lengthening by distraction was performed in a 6-year-old severely affected Treacher-Collins syndrome patient who was tracheostomy dependent. As previously reported, this procedure permitted tracheostomy removal once distraction was complete. Now that the patient is skeletally mature, the long-term results of this intervention are reported with regard to his clinical outcome and an assessment of the anatomical changes in the upper airway during growth. Although the distraction could be considered a success in that it enabled permanent decannulation and improved the minimum cross-sectional area of the upper airway, there was no further increase in the minimum cross-sectional area of the upper airway during childhood growth. It is significant that the abnormal growth pattern of the mandible, which is characteristic of this syndrome, did not alter from its preoperative pattern once distraction was completed.
Publisher: Springer Science and Business Media LLC
Date: 09-07-2020
DOI: 10.1038/S41598-020-68261-2
Abstract: Previous studies of global binding patterns identified the epigenetic factor, EZH2, as a regulator of the homeodomain-only protein homeobox (HOPX) gene expression during bone marrow stromal cell (BMSC) differentiation, suggesting a potential role for HOPX in regulating BMSC lineage specification. In the present study, we confirmed that EZH2 direct binds to the HOPX promoter region, during normal growth and osteogenic differentiation but not under adipogenic inductive conditions. HOPX gene knockdown and overexpression studies demonstrated that HOPX is a promoter of BMSC proliferation and an inhibitor of adipogenesis. However, functional studies failed to observe any affect by HOPX on BMSC osteogenic differentiation. RNA-seq analysis of HOPX overexpressing BMSC during adipogenesis, found HOPX function to be acting through suppression of adipogenic pathways associated genes such as ADIPOQ, FABP4, PLIN1 and PLIN4. These findings suggest that HOPX gene target pathways are critical factors in the regulation of fat metabolism.
Publisher: Wiley
Date: 02-2010
DOI: 10.1111/J.1601-6343.2009.01478.X
Abstract: The number of publications on the oral features in Apert syndrome is limited. The present study investigated dental tissues in Apert syndrome histologically, to determine the nature and extent of anomalies, to provide some insight into the nature of the condition, and to explain how observed anomalies may affect the dental management of in iduals with Apert syndrome. Extracted primary and secondary teeth were collected from patients with Apert who had attended the Australian Craniofacial Unit, Adelaide, South Australia. The total study s le comprised 13 in iduals, aged from 14 to 21 , with nine men and four women. A total of 40 teeth were available for histological examination (the number belonging to each in idual varied from 2 to 5 per patient). The teeth were sectioned longitudinally, and one-half of each tooth underwent decalcification. Sections were stained with H&E for routine histological examination. Ground sections were prepared from undecalcified tooth halves. Histological assessment of the dental hard tissues revealed an intact enamel and dentinal structure but some irregularities were noted in the region of the dentino-enamel junction (DEJ), which could affect caries progression and also make dental management more difficult. This study identified histological anomalies of the DEJ of Apert syndrome teeth. An improved appreciation of the nature and extent of dental anomalies in Apert syndrome should assist clinicians when undertaking management of affected in iduals.
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.JOCN.2006.07.001
Abstract: We report 41 cases of non-syndromic isolated sagittal synostosis in which evaluation of intracranial volumes was undertaken. Twenty-six were male and fifteen were female. The measured intracranial volumes were then compared with normal age-corrected values. We have found that intracranial volumes were significantly larger than the normal population intracranial volumes in both sexes. However the statistical significance of this finding was much greater in females, (p<0.00002), than males (p T (Asn294Asn) in FGFR3 (fibroblast growth factor Receptor 3) on genetic testing were compared to age and sex matched cases of non-syndromic sagittal synostosis (without an underlying mutation) which confirmed that there were no discernable differences in intracranial volumes between the two groups. We conclude that this investigation supports the role of cranial re-shaping to improve cosmesis as the primary aim of surgical correction in this condition, in the absence of raised intracranial pressure.
Publisher: SAGE Publications
Date: 10-1996
DOI: 10.1016/S0266-7681(96)80151-3
Abstract: Three cases of unilateral duplication of the little finger in children with Apert's syndrome are presented. They provide additional evidence that the hands in Apert's syndrome are not always symmetrically affected.
Publisher: SAGE Publications
Date: 1996
DOI: 10.1177/014107689608900116
Abstract: Congenital gingival granular cell tumours are rare lesions which have only occasionally been reported in the UK. Clinical features are of a benign lesion which occurs almost exclusively in newborn, Caucasian females and the anterior maxilla is the commonest site. Treatment consists of local excision and is curative. The terminology concerning this condition has been rather confused because of uncertainty regarding the histogenesis of these tumours and the similar histological appearance to adults granular cell myoblastoma occurring at other intraoral sites. The exact histogenesis of these tumours remains unresolved and they may be hamartomata. We describe a new case occurring within the UK, which illustrates many of the common clinical features of the condition, with an accompanying literature review.
Publisher: Wiley
Date: 12-06-2020
Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
Date: 05-1996
Publisher: Elsevier BV
Date: 1995
DOI: 10.1016/0020-1383(95)90552-9
Abstract: Fractures of the facial skeleton in children are uncommon. This study presents the results of 139 children who sustained a total of 161 such fractures and were admitted to the Royal Hospital for Sick Children, Edinburgh, between January 1983 and December 1992. The male to female ratio was 3:1 and the highest incidence was at age 10 years. Analysis of fracture patterns showed that despite differences in anatomy, the fracture patterns were similar to those occurring in adults, but the relative proportion of each fracture type was different in children. Nasal fractures occurred most frequently (54 per cent), mandibular fractures constituted 30 per cent, and middle third fractures only 16 per cent. Falls, sporting injuries and road traffic accidents (RTA) were the major causes of these injuries. Injuries sustained in RTA were most likely to have involved cyclists or pedestrians in contrast to earlier series which have identified these injuries mainly among car passengers. No deaths were recorded and most patients made a complete recovery, although a few required secondary surgery for complications. This taken in conjunction with the findings of both high numbers of associated injuries, and increased severity commonly occurring in both mandibular and middle third injuries leads to the suggestion that these should be treated in centres where multidisciplinary management can easily be coordinated.
Publisher: Springer Science and Business Media LLC
Date: 12-2020
DOI: 10.1186/S13287-020-02051-5
Abstract: During development, excessive osteogenic differentiation of mesenchymal progenitor cells (MPC) within the cranial sutures can lead to premature suture fusion or craniosynostosis, leading to craniofacial and cognitive issues. Saethre-Chotzen syndrome (SCS) is a common form of craniosynostosis, caused by TWIST-1 gene mutations. Currently, the only treatment option for craniosynostosis involves multiple invasive cranial surgeries, which can lead to serious complications. The present study utilized Twist-1 haploinsufficient ( Twist-1 del/+ ) mice as SCS mouse model to investigate the inhibition of Kdm6a and Kdm6b activity using the pharmacological inhibitor, GSK-J4, on calvarial cell osteogenic potential. This study showed that the histone methyltransferase EZH2 , an osteogenesis inhibitor, is downregulated in calvarial cells derived from Twist-1 del/+ mice, whereas the counter histone demethylases, Kdm6a and Kdm6b , known promoters of osteogenesis, were upregulated. In vitro studies confirmed that siRNA-mediated inhibition of Kdm6a and Kdm6b expression suppressed osteogenic differentiation of Twist-1 del/+ calvarial cells. Moreover, pharmacological targeting of Kdm6a and Kdm6b activity, with the inhibitor, GSK-J4, caused a dose-dependent suppression of osteogenic differentiation by Twist-1 del/+ calvarial cells in vitro and reduced mineralized bone formation in Twist-1 del/+ calvarial explant cultures. Chromatin immunoprecipitation and Western blot analyses found that GSK-J4 treatment elevated the levels of the Kdm6a and Kdm6b epigenetic target, the repressive mark of tri-methylated lysine 27 on histone 3, on osteogenic genes leading to repression of Runx2 and Alkaline Phosphatase expression. Pre-clinical in vivo studies showed that local administration of GSK-J4 to the calvaria of Twist-1 del/+ mice prevented premature suture fusion and kept the sutures open up to postnatal day 20. The inhibition of Kdm6a and Kdm6b activity by GSK-J4 could be used as a potential non-invasive therapeutic strategy for preventing craniosynostosis in children with SCS. Pharmacological targeting of Kdm6a/b activity can alleviate craniosynostosis in Saethre-Chotzen syndrome. Aberrant osteogenesis by Twist-1 mutant cranial suture mesenchymal progenitor cells occurs via deregulation of epigenetic modifiers Ezh2 and Kdm6a/Kdm6b. Suppression of Kdm6a- and Kdm6b-mediated osteogenesis with GSK-J4 inhibitor can prevent prefusion of cranial sutures.
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.JCMS.2005.01.005
Abstract: The potential problem of growth anomalies affecting a mandible following a fracture of a mandibular condyle in childhood is well established. However, there have been no previous reports of this phenomenon affecting other fracture sites in the mandible. Two patients who had parasymphyseal fractures treated in childhood presented at skeletal maturity with hyperostosis at the fracture site, producing chin asymmetry in their teens. In both cases the hyperostosis produced significant chin asymmetry without disturbance of the occlusion. Both patients were managed with corrective genioplasty. These cases reinforce the previous recommendations regarding the need for long-term follow-up of children who sustain facial fractures of the mandible, and that the protocol should be expanded to include parasymphyseal fractures as well as fractures of the condyle.
Publisher: Springer Science and Business Media LLC
Date: 05-08-2021
DOI: 10.1007/S00381-021-05313-6
Abstract: To investigate the incidence of persistent, open metopic sutures in contemporary Australians aged 24 months and older. Metopic suture evaluation was conducted on retrospective cranial/cervical computed tomography scans of patients aged 24 to 252 months who presented to the Women's and Children's Hospital in Adelaide, Australia, between 2010 and 2020. Suture ossification was graded according to Lottering scoring system based on 4 stages, on three-dimensional volume-rendered reconstructions (stage 1: fibrous tissue interface, stage 2: commenced fusion, stage 3: complete fusion and stage 4: obliterated suture). The complete persistent sutures were classified as stage 1. Partially closed sutures were classified into stages 2 and 3, while completely closed sutures were defined as stage 4. One thousand thirty-four patients (61.2% male and 38.8% female) were included, with a mean age at scan of 66 months. More than half of patients were subject to scanning due to closed-head injuries. The incidence of persistent (completely open) metopic suture was 4.8% (2.3% in males and 2.5% in females). In comparison, a partially closed metopic suture was found in 6.3% of the study cohort, with the remaining sutures located along the metopic suture line, at the glabella, mid-part of the suture, bregma and glabella-bregma areas. The prevalence of persistent metopic sutures in our study of the Australian population is 4.8%, and it is equally distributed between the genders. The pattern of suture closure can commence from any location along the suture line, which is in contrast to the existing literature.
Publisher: Springer Science and Business Media LLC
Date: 31-07-2009
DOI: 10.1007/S00381-009-0955-Y
Abstract: Chordomas are rare slow growing, locally destructive tumours originating from remnants of the primitive notocord and are found most commonly in the clivus and saccrococcygeal region. These tumours usually present in early adult life but on occasion can present in childhood. The combination of the skull base location and paediatric patient size makes access to these tumours particularly challenging. We report a multidisciplinary technique used in two cases in children where a modified extended palatal split was undertaken to allow greater access for tumour excision. This approach allows for good access to the skull base region to allow for maximal tumour resection. This technique also appears to have minimal impact on palatal function and no adverse effects on the upper airway management.
Publisher: Wiley
Date: 2006
Publisher: Springer Science and Business Media LLC
Date: 14-03-1997
Abstract: The authors describe the clinical and radiological findings in a case of non-syndromic craniosynostosis affecting multiple sutures, in which the intracranial venous drainage was grossly anomalous. Investigation by magnetic resonance imaging and angiography revealed that almost all of the intracranial venous blood was draining from the dural sinuses transosseoussly via enlarged emissary veins to the external jugular veins and the vertebral veins. Although present, both internal jugular veins were small. This discovery represented a contraindication for the vault expansion surgery that had been recommended as treatment for the patient's raised intracranial pressure, and it has important implications for the management of all types of craniosynostosis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2006
Publisher: Elsevier BV
Date: 05-2005
DOI: 10.1016/J.IJPORL.2004.12.004
Abstract: Parry-Romberg disease (or hemifacial atrophy) is a rare condition affecting the face. It commences in childhood but its aetiology remains unknown, and is sporadic. Two cases are presented who were biological first cousins. We believe that this is the first recorded ex le of this condition occurring in family members.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2006
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2009
Publisher: Wiley
Date: 11-10-2013
DOI: 10.1002/AJMG.C.31378
Abstract: Craniosynostosis is one of the most common craniofacial disorders encountered in clinical genetics practice, with an overall incidence of 1 in 2,500. Between 30% and 70% of syndromic craniosynostoses are caused by mutations in hotspots in the fibroblast growth factor receptor (FGFR) genes or in the TWIST1 gene with the difference in detection rates likely to be related to different study populations within craniofacial centers. Here we present results from molecular testing of an Australia and New Zealand cohort of 630 in iduals with a diagnosis of craniosynostosis. Data were obtained by Sanger sequencing of FGFR1, FGFR2, and FGFR3 hotspot exons and the TWIST1 gene, as well as copy number detection of TWIST1. Of the 630 probands, there were 231 who had one of 80 distinct mutations (36%). Among the 80 mutations, 17 novel sequence variants were detected in three of the four genes screened. In addition to the proband cohort there were 96 in iduals who underwent predictive or prenatal testing as part of family studies. Dysmorphic features consistent with the known FGFR1-3/TWIST1-associated syndromes were predictive for mutation detection. We also show a statistically significant association between splice site mutations in FGFR2 and a clinical diagnosis of Pfeiffer syndrome, more severe clinical phenotypes associated with FGFR2 exon 10 versus exon 8 mutations, and more frequent surgical procedures in the presence of a pathogenic mutation. Targeting gene hot spot areas for mutation analysis is a useful strategy to maximize the success of molecular diagnosis for in iduals with craniosynostosis.
Publisher: Informa UK Limited
Date: 08-2019
DOI: 10.2147/IJN.S202090
Publisher: Oxford University Press (OUP)
Date: 09-01-2015
DOI: 10.1111/BJD.14263
Abstract: Hypertrophic scarring carries a large burden of disease, including disfigurement, pain and disability. There is currently no effective medical treatment to reduce or prevent hypertrophic scarring. Flightless I (Flii), a member of the gelsolin family of actin remodelling proteins, is an important negative regulator of wound repair. The objective of this study was to investigate the role of Flii as a potential regulator of hypertrophic scarring. Using human skin s les and an animal model of bleomycin-induced hypertrophic scarring in mice that overexpress or have reduced expression of Flii, we investigated its effect on dermal fibrosis and hypertrophic scarring. Flii expression was increased in human burns and hypertrophic scars. A similar increase in Flii was observed in hypertrophic scars formed in mice post-treatment with bleomycin. However, Flii-deficient (Flii(+/-) ) mice had reduced scarring in response to bleomycin evidenced by decreased dermal thickness, smaller cross-sectional scar areas, fewer myofibroblasts and a decreased collagen I/III ratio. In contrast, bleomycin-treated Flii-overexpressing mice (Flii(Tg/Tg) ) showed increased scar dermal thickness, larger cross-sectional scar areas, more myofibroblasts and an increased collagen I/III ratio. Injecting developing scars with a Flii neutralizing antibody led to a significant reduction in the size of the scars and a reduction in the collagen I/III ratio. This study identifies Flii as a profibrotic agent that contributes to excessive scar formation. Reducing its activity using neutralizing antibodies is a promising approach for reducing hypertrophic scarring.
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.BJPS.2007.01.079
Abstract: Odontogenic keratocysts in children are uncommon. They are cysts of the jaws that have a tendency for recurrence and are usually seen in adults. We report an exceptionally rare case in a young child and discuss its management.
Publisher: Elsevier BV
Date: 06-2003
DOI: 10.1016/S0007-1226(03)00130-9
Abstract: Hemifacial microsomia is the second most common facial clefting condition after cleft lip and palate. The deformity affects the skeleton and soft tissues in the temporal region of the affected side, although the degree of involvement is markedly variable. We describe a modification of surgical technique in a skeletally mature case who had previously undergone mandibular reconstruction with a costochondral graft.
Publisher: Springer Science and Business Media LLC
Date: 18-04-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2012
Publisher: Springer Science and Business Media LLC
Date: 14-09-2018
DOI: 10.1007/S00381-018-3957-9
Abstract: Metopic synostosis is a craniofacial condition characterised by the premature fusion of the metopic suture. This early fusion restricts frontal bone growth [17] and has significant impacts on the developing infant during a critical phase of rapid growth and development [4]. Diagnosis of the condition is usually achieved by clinical assessment, followed by a three-dimensional computed tomography (3D CT) scan, verifying premature metopic suture fusion. This retrospective study aims to investigate the timing of metopic suture fusion in the developing infant in an Australian subpopulation. The study evaluates metopic suture fusion in 258 cranial 3D CT scans of children aged 0-24 months over a 5-year period (2011-2016), scanned at Women's and Children's Hospital. The findings suggest that the age range over which physiologic metopic suture fusion occurs is larger than previously reported. The approximate range for physiologic fusion was found to be 3-19 months and patients with fusion within this range can be considered normal. Complete suture fusion is expected by 19 months. Additionally, results indicate suture fusion prior to 3 months is abnormal and diagnostically indicative of metopic synostosis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2020
DOI: 10.1097/SCS.0000000000006232
Abstract: The impact of fronto-orbital advancement (FOA) on frontal sinus development and function is anecdotally variable. The aim of this study was to assess the impact of FOA on development of frontal sinuses, and additionally to identify the complications that might arise out of such procedures. This was a retrospective case-control study. Non-syndromic and syndromic craniosynostosis patients (n = 58) who underwent FOA at an early age and also had a skull radiograph or CT scan after the age of 12 were selected. Age matched trauma patients with CT scans done beyond 12 years of age were used as controls. Age at first FOA surgery, total number of procedures and age at imaging was noted. Presence or absence of frontal sinuses was assessed using imaging studies initially. Patients with a formed frontal sinus and a CT scan were further chosen for volumetric studies. Complications related to frontal sinus and secondary surgeries were recorded. One of 27 non-syndromic patients had absent frontal sinuses. Seven of 31 syndromic patients had absent sinuses. Among 20 controls, only 1 patient did not develop frontal sinuses. The mean age at first FOA was 11.81 months and 18.25 months for non-syndromic and syndromic groups, respectively. The average number of procedures before 12 years of age was 1.25 and 1.51 for non-syndromic and syndromic patients, respectively. The mean age at imaging was 17.74, 20.96, and 20.25 years for non-syndromic, syndromic and control groups, respectively. The mean frontal sinus volumes were 13050.36, 15039.02, and 8459.48 mm 3 for non-syndromic, syndromic and control groups, respectively. In conclusion, FOA does not seem to have an impact on rate of pneumatization in the background of similar rates in the non-syndromic and control groups. The low pneumatization rate in syndromic group might be a virtue of the disease itself. There were significant frontal sinus complications that occurred after fronto orbital advancement and this should be borne in mind during the surgical consenting process.
Publisher: Wiley
Date: 04-12-1998
DOI: 10.1002/(SICI)1096-8628(19981204)80:4<439::AID-AJMG27>3.0.CO;2-T
Publisher: Elsevier BV
Date: 05-2008
Publisher: Georg Thieme Verlag KG
Date: 2000
DOI: 10.1055/S-2000-7542
Abstract: It is well-recognised that recurrent disease can occur following surgery for malignancy in the head and neck region. This is particularly true of basal cell carcinoma in which recurrences may occur over many years and despite the use of different treatment modalities. Reconstruction of large defects may become increasingly difficult and can be optimally managed by free tissue transfer. The authors report a case of basal cell carcinoma that has required treatment for over 20 years, unique in that on five different occasions, free flaps have been used for reconstruction.
Publisher: Elsevier BV
Date: 12-1997
DOI: 10.1016/S1010-5182(97)80039-X
Abstract: Synovial sarcoma (SS) is a rare mesenchymal entity that represents 5-10% among soft tissue sarcomas (STS). Primary renal synovial sarcoma (PRSS) is an uncommon, rapidly growing tumor, with potential metastatic dissemination. The main prognostic factors of PRSS include tumor size and histologic grade, while translocation t (X 18) (p11.2 q11.2) (fusion of SYT gene -chromosome 18- with SSX genes (1, 2 or 4)-chromosome X) is the most common pathognomonic sign. Aggressive surgical resection of the tumor along with concomitant regional lymphadenectomy is the treatment of choice for PRSS, while additional en bloc resection of the adjacent affected organs is often performed. To date, the role of preoperative or postoperative chemotherapy remains equivocal. The prognosis of patients with PRSS is poor, as the 5-year survival rate is only 20-30% and further deteriorates when a high mitotic activity is detected. Local recurrence even after complete R0 surgical excision remains the most frequent cause of death. The aim of this review was to meticulously discuss clinical features, histogenesis, and morphological and immunochemical findings of PRSS, while the role of current diagnostic and therapeutic management of this aggressive neoplasm was emphasized.
Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
Date: 08-2005
DOI: 10.3171/PED.2005.103.2.0137
Abstract: In recent years, comparisons between intracranial volumes (ICVs) in patients with craniosynostosis and healthy patients have given variable results, leading to questions regarding the validity of the normal reference material and the comparability of the measurement techniques. In this study, ICVs in patients with nonsyndromal craniosynostosis without previous surgical intervention were compared with the ICVs of a normal population of European descent determined using the same method for each group. Determination of ICV was based on measuring the area of intersection in each computerized tomography slice. For comparisons the ICV measurements for each patient were standardized with regard to age and sex by expressing them in terms of the standard deviation score. Only the group of boys with metopic synostosis had a tendency toward smaller ICV than did healthy boys (p = 0.04). Partitioning the male metopic data into age groups younger and older than 7 months of age revealed that the younger children had normal ICVs, whereas the older children had, on average, smaller ICVs (p = 0.02). Both the female sagittal synostosis and the male unilateral coronal synostosis groups had larger than normal ICVs, both with a probability value less than 0.001. No evidence was found that the ICVs of patients with nonsyndromal craniosynostosis are smaller than those of normal children, except for boys older than 7 months of age with metopic synostosis. This finding may have implications for the timing of surgical intervention for these patients. The indications are that interventions should be focused less on ICV and more on normalizing craniofacial shape and promoting normal development.
Publisher: Wiley
Date: 18-10-2011
DOI: 10.1111/J.1601-6343.2011.01529.X
Abstract: To investigate tooth size and dental arch dimensions in Malays using a stereophotogrammetric system. The s le consisted of 252 subjects with ages ranged from 13 to 30 years. Images of dental casts were captured by stereophotogrammetry and selected variables were measured using a three-dimensional (3D) imaging system. Sex differences and changes associated with age were assessed, and interrelationships between different variables were explored within the study group. Men had significantly larger mesio-distal crown widths and dental arch dimensions than women (p < 0.05). None of the dental arch dimensions or mesio-distal crown widths showed a significant change because of age except the widths of the upper canine, lower first molar and central incisor. Significant correlations of tooth size with dental arch dimensions were found, particularly with arch lengths and perimeters. A principal component analysis showed interrelationships between the majority of tooth size variables with inter-canine width, arch length and perimeter distances. This study has established new reference data for tooth size and arch dimensions in Malays and demonstrated patterns of variation that are relevant to anthropologists interested in making comparisons within and between different populations and also to clinicians developing treatment plans for their patients. The study confirmed the accuracy of the 3D photogrammetric method for measuring dental casts.
Publisher: Informa UK Limited
Date: 08-09-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-1998
DOI: 10.1097/00001665-199805000-00002
Abstract: Craniosynostosis may occur in conjunction with limb and visceral anomalies in more than 100 syndromes and may include anomalies of the elbow. Apert's, Pfeiffer's, Crouzon's, and Saethre-Chotzen syndrome have been linked with anomalies of the elbow, but the incidence and severity of such anomalies is unknown. A prospective radiographic study was undertaken to establish the types, incidence, and severity of elbow anomalies in patients with either Apert's, Pfeiffer's, Crouzon's, or Saethre-Chotzen syndrome attending the Craniofacial Centre at Great Ormond Street Hospital during a 12-month period. This study showed that elbow anomalies were very common in Apert's and Pfeiffer's syndrome, but less so in Crouzon's syndrome. The elbows in all patients with Saethre-Chotzen syndrome were normal. A range of anomalies was seen, with overlap between the syndromes. The severest anomaly seen in children with Crouzon's, Pfeiffer's, and Apert's syndrome was complete synostosis, which may require surgical intervention in due course. The results of this study suggest that the incidence of elbow anomalies in Apert's, Pfeiffer's, and Crouzon's syndrome is higher than the current literature suggests. Synostosis can be so severe that orthopedic review as part of the management of these children may be beneficial and may become increasingly important as more of these children survive into adulthood.
Publisher: Elsevier BV
Date: 06-1999
Abstract: The surgical management of an extensive pleomorphic adenoma arising within deep lobe of the parotid gland is presented.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2012
Abstract: Achieving efficient introduction of plasmid DNA into primary cultures of mammalian cells is a common problem in biomedical research. Human primary cranial suture cells are derived from the connective mesenchymal tissue between the bone forming regions at the edges of the calvarial plates of the skull. Typically they are referred to as suture mesenchymal cells and are a heterogeneous population responsible for driving the rapid skull growth that occurs in utero and postnatally. To better understand the molecular mechanisms involved in skull growth, and in abnormal growth conditions, such as craniosynostosis, caused by premature bony fusion, it is essential to be able to easily introduce genes into primary bone forming cells to study their function. A comparison of several lipid-based techniques with two electroporation-based techniques demonstrated that the electroporation method known as nucleofection produced the best transfection efficiency. The parameters of nucleofection, including cell number, amount of DNA and nucleofection program, were optimized for transfection efficiency and cell survival. Two different genes and two promoter reporter vectors were used to validate the nucleofection method and the responses of human primary suture mesenchymal cells by fluorescence microscopy, RT-PCR and the dual luciferase assay. Quantification of bone morphogenetic protein (BMP) signalling using luciferase reporters demonstrated robust responses of the cells to both osteogenic BMP2 and to the anti-osteogenic BMP3. A nucleofection protocol has been developed that provides a simple and efficient, non-viral alternative method for in vitro studies of gene and protein function in human skull growth. Human primary suture mesenchymal cells exhibit robust responses to BMP2 and BMP3, and thus nucleofection can be a valuable method for studying the potential competing action of these two bone growth factors in a model system of cranial bone growth.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2011
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2008
End Date: 2010
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2018
End Date: 2020
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2021
End Date: 2024
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2017
End Date: 2019
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2018
End Date: 2020
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2014
End Date: 2017
Funder: National Health and Medical Research Council
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