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Biomedical subjects

D J David

Publications and source records attributed to D J David.

At least 37 records · Page 2Linked to original sources

In vivo electrochemical studies of dopamine clearance in subregions of rat nucleus accumbens: differential properties of the core and shell.

The dopamine (DA) uptake/clearance properties of the DA transporter (DAT) in the core and shell of the nucleus accumbens were measured using in vivo electrochemical recordings. Calibrated amounts of a DA solution were pressure-ejected from a micropipette/electrode assembly placed in the core or shell of the nucleus accumbens in anesthetized male Fischer 344 rats. Initial studies in the two brain regions revealed that the core and shell have different DA clearance properties as measured by the extracellular DA signal amplitudes, clearance times, and clearance rates. Although the same number of picomoles of DA were applied, DA clearance signals recorded in shell had significantly greater amplitudes but faster clearance rates than those recorded in the core. Systemic administration of 20 mg/kg cocaine, a monoamine transporter inhibitor, greatly increased the signal amplitude from the locally applied DA in both the core and shell. Signal amplitudes were increased to a greater extent in the shell, compared with the core, after cocaine administration. However, cocaine affected the clearance time of DA only in the core and the DA clearance rate only in the shell. Taken together with previously reported data, these studies further support differential activity of the DAT in the core versus shell subregions of the nucleus accumbens. In addition, these data indicate that DATs are more sensitive to the effects of psychomotor stimulants, such as cocaine, in the shell of the nucleus accumbens.

Animals↗

Speech changes after maxillary advancement in 40 cleft lip and palate patients.

In this study, we retrospectively investigated speech intelligibility changes in 40 patients at the Australian Cranio-Facial Unit who underwent Le Fort I maxillary advancement between 1978 and 1995. Resonance, articulation, and velopharyngeal sphincteric function, which were assessed before and after surgery, were analyzed in conjunction with details of the surgery in an attempt to identify the factors affecting speech intelligibility. Of the 40 patients, 10 experienced improved speech (improved intelligibility group), 18 demonstrated no detectable changes in speech (unchanged intelligibility group), and 12 presented with worsened speech intelligibility (deteriorated intelligibility group). The average amount of advancement was 9.4 mm in the improved and unchanged intelligibility groups and 12.2 mm in the deteriorated intelligibility group. There was a statistically significant difference in the average amount of advancement between the improved and unchanged groups and the deteriorated intelligibility group. In the improved intelligibility group, 9 patients demonstrated improved articulation and 7 had reduced hyponasality. Conversely, in the deteriorated intelligibility group, 10 patients demonstrated increased hypernasality. Intelligibility ratings appeared to depend on the balance between the benefits of amelioration of hyponasality and misarticulations and the debit of increased hypernasality. The amount of maxillary advancement has a direct bearing on speech intelligibility. The amelioration of speech intelligibility improves if the amelioration of distorted articulation and hyponasality overrides any increase in hypernasality.

Adolescent↗

Unilateral lambdoid synostosis: morphological characteristics.

The accurate diagnosis of unilateral lambdoid synostosis versus deformational occipital plagiocephaly has remained a complex and controversial issue in the field of craniofacial surgery. Over the past 30 years, numerous studies have been published describing the treatment for "lambdoid synostosis," the diagnosis having been ascribed despite radiographically patent sutures and pathology specimens displaying fibrous, nonfused suture lines. Over the past 16 years, 204 patients with unilateral occipital plagiocephaly have been seen at our unit, only 2 of whom (approximately 1%) manifested the clinical, radiographic, and pathological features of true lambdoid synostosis. Radiographically, there was evidence of sutural fusion on plain films and two- and three-dimensional computed tomographic scans. Clinical features included a trapezoid head shape as viewed from the vertex, ipsilateral occipitomastoid bossing, contralateral parietal bossing, and anteroinferior ear displacement. Pathology specimens showed bony sutural fusion. These characteristics are contrasted to those of patients with deformational plagiocephaly and those found in other published studies on occipital plagiocephaly.

Craniosynostoses↗

Pharyngoplasty in patients with cleft lip and palate after maxillary advancement.

The development of velopharyngeal incompetence and increased hypernasality after maxillary advancement has been described previously by several authors. If speech and velopharyngeal function deteriorate after maxillary advancement, pharyngoplasty is frequently the treatment procedure of choice because of the natural cause of the deficit. Of 91 cleft lip and palate patients who have undergone maxillary advancement at the Australian Cranio-Facial Unit, 23 patients received a pharyngoplasty after surgery. Thirteen of these patients who had pre- and postoperative speech evaluations were included in this study. Of the 13 patients, six patients received a superiorly based pharyngeal flap, two patients underwent an orticocheal pharyngoplasty, and five patients received either a revision or augmentation of the previous flap based on results of preoperative examinations. Serial nasendoscopic evaluations were available for 11 of these 13 patients, and they demonstrated that velopharyngeal function improved after pharyngoplasty in six patients and was unchanged in five patients. Of the 13 patients, 10 improved and three patients were unchanged on an intelligibility rating. Nine of the 13 patients demonstrated decreased hypernasality and four patients were unchanged. Hyponasality decreased in two patients increased in one patient, and was unchanged in one patient. Because the results obtained are considered acceptable, the authors conclude that pharyngoplasty can be used effectively to treat velopharyngeal dysfunction subsequent to Le Fort I maxillary advancement.

Adolescent↗

Computer tomography determined intracranial volume of infants with deformational plagiocephaly: a useful "normal"?

Over the last 10 years, children with deformational (nonsynostotic) plagiocephaly have undergone computed tomography scans using the same protocols as children with lambdoid craniosynostosis because of their similarly distorted head shapes. These children are believed to have normal intracranial volume. Given the recent questioning of what is the normal range of intracranial volume in human populations, the authors have undertaken a comparison of the intracranial volume of children with deformational plagiocephaly and Lichtenberg's normal population (Lichtenberg R. Radiographie du crane de 226 enfants normaux de la naissance a 8 ans: Impressions digitiformes, capacite, angles et indices [thesis]. Paris: University of Paris, 1960). The intracranial volume was determined for 20 females and 46 males with deformational plagiocepahly ranging in age from 2.5 to 20.7 months using computed tomography scan data. Although no significant differences were found for the females, the authors found that the intracranial volume of the males with deformational plagiocephaly were significantly larger than Lichtenberg's population. The authors conclude that this is because Lichtenberg's data do not adequately reflect the normal range of intracranial volume for males ranging in age from 2.5 to 20.7 months, rather than gender differences associated with deformational plagiocephaly. Further, until a more suitable normal becomes available, the deformational (nonsynostotic) plagiocephaly data could be used as substitute normal reference material in the measured age range for assessment of the intracranial volumes of children with craniosynostosis.

Analysis of Variance↗

Transcranial correction of orbital neurofibromatosis.

Neurofibromatosis is a systemic disease that often produces striking disfigurement. Orbital manifestations are common and include sphenoid dysplasia with or without infiltration of the periorbital soft tissues. The resultant deficiency of the posterolateral orbital wall may lead to protrusion of the temporal lobe into the orbit, displacement of the globe, and pulsatile exophthalmos. Treatment at our unit has consisted of transcranial orbital reconstruction with bone grafts and periorbital soft-tissue correction. Observation of complete bone graft resorption in one patient prompted an assessment of the Australian Craniofacial Unit's experience with particular attention paid to the stability of operative correction. Of 36 patients with head and neck neurofibromatosis treated during the period from 1981 to 1995, 14 patients underwent transcranial correction of orbital deformities secondary to sphenoid dysplasia. The treatment and outcomes of this transcranial group are reviewed. The most notable finding was that of recurrent globe pulsation in four patients following initial resolution. Computed tomography scans have documented partial to complete bone graft resorption in three of these patients. Titanium mesh is now being utilized to provide a more durable reconstruction.

Adolescent↗

Computer generated mandibular model: surgical role.

A life-size nylon model of a traumatized mandible was produced from CT scan data by the process of laser sintering. The model was used for pre-operative planning and for production of surgical aids in order to facilitate the restoration of a large bony defect. Vascularized iliac crest bone was harvested, titanium implants placed and the bone then grafted to the mandible.

Adult↗

Mutation detection in FGFR2 craniosynostosis syndromes.

Five autosomal dominant craniosynostosis syndromes (Apert, Crouzon, Pfeiffer, Jackson-Weiss and Crouzon syndrome with acanthosis nigricans) result from mutations in FGFR genes. Fourteen unrelated patients with FGFR2-related craniosynostosis syndromes were screened for mutations in exons IIIa and IIIc of FGFR2. Eight of the nine mutations found have been reported, but one patient with Pfeiffer syndrome was found to have a novel G-to-C splice site mutation at-1 relative to the start of exon IIIc. Of those mutations previously reported, the mutation C1205G was unusual in that it was found in two related patients, one with clinical features of Pfeiffer syndrome and the other having mild Crouzon syndrome. This degree of phenotypic variability shows that the clinical features associated with a specific mutation do not necessarily breed true.

Adult↗

The Apert syndrome hand: pathologic anatomy and clinical manifestations.

The Apert syndrome hand demonstrates many typical clinical features including syndactyly, symbrachyphalangism, and growth disturbances. This is due to the grossly abnormal anatomy of both the skeletal and soft-tissue structures associated with a progressive disease process. This paper presents a clinical, radiologic, and histologic analysis of the Apert syndrome hand anatomy and correlates it with the clinical manifestations. It also links hand and craniofacial dysplasia to other regions of the skeleton as well as the overall disease process. From our analysis, we conclude that there is a genetic anomaly causing variable and uncoordinated differentiation of the mesenchyme at the time of embryologic separation into its various skeletal components, particularly in the distal limb bud and craniofacial skeleton. This disease process continues postnatally in endochondral bone growth center malformation and malfunction as well as ectopic cartilage ossification in soft tissues. We discuss the role of abnormal musculotendinous anatomy and altered biomechanical forces in relation to these processes.

Acrocephalosyndactylia↗

Imaging of the Apert syndrome hand using three-dimensional CT and MRI.

Imaging of the Apert syndrome hand is usually done with plain x-rays. This gives only a limited assessment of the grossly abnormal anatomy. Computed tomography (CT) and magnetic resonance imaging (MRI) have the ability to comprehensively demonstrate the spatial arrangement of the bones as well as the anatomy of the soft-tissue structures. This paper demonstrates the use of these two imaging modalities in the complex Apert syndrome hand to improve surgical planning and treatment.

Acrocephalosyndactylia↗

The influence of maxillary dentures on mid-facial fracture patterns.

The presence of upper arch dentures modifies fracture patterns occurring in mid-facial trauma. The fracture patterns of 16 upper denture wearers suffering maxillary fractures were retrospectively studied. Mid-facial fractures in this group were predominantly of the Le Fort I type and in 14 patients demonstrated an atypical fracture path with a vertical fracture passing from the main Le Fort I fracture to the inferior orbital rim. Full upper arch dentures generally protected the upper alveolus from fracture but, where there was discontinuity of the prosthesis, alveolar fractures mirroring the edge of the denture as it crossed the alveolar region were seen. These findings should alert the clinician to the possibility of unusual maxillary fractures in denture wearers and aid our understanding of fracture patterns in the mid-facial skeleton.

Adult↗

Intraorbital tissue expansion in the management of congenital anophthalmos.

Seven cases of intraorbital tissue expansion for the treatment of congenital anophthalmos or microphthalmos are presented. The ages of the patients at insertion of the expander ranged from 4 months to 8 years. A 4 ml spherical tissue expander with a remote injection port was inserted into the affected orbit via a bicoronal approach. Expansion periods ranged between 4 months and 3 years and are continuing in 2 patients. Results were assessed by clinical examination, comparison of photographs, 3D CT scans and orbital measurements taken from axial CT scans which were compared with established normal values. Results confirmed enlargement of the orbit with expansion. Long-term expansion over several years established near normal bony growth patterns. Placement of the expander within the orbital soft tissue cone resulted in more symmetrical expansion than subperiosteal placement. An osteotomy releasing the lateral orbital wall in older children allows expansion of the orbit and may reduce the incidence of expander extrusion. Although intraorbital tissue expansion successfully induces orbital growth, improvement in the form and size of the congenitally deficient eyelids is less marked.

Anophthalmos↗

A comparative study of miniplates used in the treatment of mandibular fractures.

The purposes of this study were to investigate the differences in mechanical properties of major miniplating systems used for noncompression miniplate osteosynthesis of mandibular fractures and to determine whether these properties influence treatment outcome. The study was conducted in two parts. First, six of the major miniplate systems currently used at the Royal Adelaide Hospital were subjected to bending tests at the University of Adelaide Engineering Department to quantify the relative stiffness of each plate. Second, a prospective sample of patients presenting with mandibular fractures was analyzed. These patients were treated with a variety of the miniplating systems. The results of treatment as a whole were compared to identify any direct benefit consequent on the miniplate selected. While significant differences in stiffness were identified between the plating systems, no significant differences in treatment outcome were identified, between the noncompression plates employed. Since no observable benefits have been identified by choice of miniplate, selection should be based on surgical preference, biocompatibility, CT compatibility and unit cost. Because of the variations in materials, design, properties, CT compatibility, and unit cost, it is important not to regard all miniplates as equal and interchangeable.

Biocompatible Materials↗

Prenatal exposure to phenytoin, facial development, and a possible role for vitamin K.

Ten patients with maxillonasal hypoplasia (Binder "syndrome"), who were prenatally exposed to phenytoin (usually in combination with other anticonvulsants), were identified retrospectively. In addition to their facial anomalies, 6 of the patients were radiographed neonatally and showed punctate calcification, characteristic of chondrodysplasia punctata. Evidence is presented that the facial abnormalities seen in these children are due to anticonvulsant-induced vitamin K deficiency, causing abnormal development of the cartilaginous nasal septum. We propose that early vitamin K supplementation of at-risk pregnancies may prevent the development of maxillonasal hypoplasia, which in some patients is severely disfiguring and causes great emotional distress. Correction of this facial defect requires surgical and dental treatment over a long period of time.

Abnormalities, Drug-Induced↗

Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome.

Apert syndrome is a distinctive human malformation comprising craniosynostosis and severe syndactyly of the hands and feet. We have identified specific missense substitutions involving adjacent amino acids (Ser252Trp and Pro253Arg) in the linker between the second and third extracellular immunoglobulin (Ig) domains of fibroblast growth factor receptor 2 (FGFR2) in all 40 unrelated cases of Apert syndrome studied. Crouzon syndrome, characterized by craniosynostosis but normal limbs, was previously shown to result from allelic mutations of the third Ig domain of FGFR2. The contrasting effects of these mutations provide a genetic resource for dissecting the complex effects of signal transduction through FGFRs in cranial and limb morphogenesis.

Acrocephalosyndactylia↗

Central nervous system imaging in Crouzon's syndrome.

Although the need to prevent the secondary effects of craniosynostosis on the central nervous system is fundamental to the practice of craniofacial surgery, the detailed structural anatomy of the central nervous system in the syndromal craniosynostoses has become the subject of recent interest. A clinical and radiographic review of a population of 59 patients with Crouzon's syndrome determined the frequency of central nervous system deformities. Twelve percent of patients had evidence of decreased mental function. Ventriculomegaly on computed tomographic scan was present in 51% and found to be of three grades: mild, moderate, and severe (hydrocephalus). This was nonprogressive in 7 of the 11 patients with follow-up computed tomographic scans. Ten patients underwent surgical release to increase intracranial space; however, 6 of these patients showed no progression in ventricular size. Nonventricular anomalies were found less frequently (14%). Central nervous system findings show fewer nonventricular anomalies than in Apert's syndrome patients, with a corresponding higher mental function. The principal anomaly of ventriculomegaly is not directly related to suture defect and may represent a primary brain abnormality. Recommendations are made for the assessment and management of patients with Crouzon's syndrome with reference to these areas.

Adolescent↗

Pfeiffer syndrome: a clinical review.

The combination of bicoronal craniosynostosis, broad thumbs and great toes, and partial variable soft tissue syndactyly of the hands and feet (i.e., Pfeiffer syndrome) classically followed a benign clinical course. A review of the clinical features of those Pfeiffer syndrome patients presenting to our unit confirm another subgroup in whom the craniofacial and associated manifestations are more extreme, with a significant risk of early demise. The early aggressive surgical management of craniostenosis, hydrocephalus, exorbitism, faciostenosis, and upper airway obstruction has provided the potential for prolonged useful survival in these cases.

Acrocephalosyndactylia↗