The concept suggesting primary excision and immediate grafting as the definitive treatment for a thermal burn is not new (1 ). To avoid the sequelae of local and systemic sepsis, early excision of burn eschar to remove all devitalized tissue has been a widely accepted method of treatment of deep burns since 1929, when Wells performed total excision and grafting of electric burns (2). While the technique has many advantages, it is not without significant complications. Haemorrhage accompanying burn wound excision can be deceptively large, as can the metabolic stress associated with large surgical procedures performed in the post-burn period (3).

Thesis (MMed (Surgical Sciences. Plastic and Reconstructive Surgery))--University of Stellenbosch, 2010. / The repair of full-thickness defects of the lower eyelids poses a challenge because a graft in combination with a flap is typically used to replace either the posterior or anterior lamella. This often results in aesthetically and functional unsatisfactory outcomes. A rotation-advancement tarso-conjunctival cheek flap, which reconstructs both posterior and anterior lamella with vascularized tissue similar to the native eyelid, is described. Nine patients underwent reconstruction with a rotation-advancement tarso-conjunctival cheek flap. The indications, complications and outcomes were evaluated. The follow-up time ranged from 6 to 60 months with an average of twenty three months. The main indication for use of this flap is full-thickness defects of the lower eyelid between 25 – 75 %, typically after tumour ablation. All the patients had a functional and aesthetically satisfactory outcome. One patient underwent a revision canthoplasty. The rotation-advancement tarso-conjunctival cheek flap adheres to basic plastic surgery principles resulting in a satisfactory outcome; (a) Vascularized tissue is used to reconstruct the defect. (b)The flap composition is similar to the native eyelid i.e. replace like with like. (c) The flap makes use of tissue that is excess and therefore limits donor morbidity.

Artificial tissue expansion is required to generate new skin prior to reconstructive surgery, in order to compensate for a deficit of healthy tissue. Hydrogel tissue expanders, which expand anisotropically, show great promise in overcoming clinical limitations in the field, thus allowing the technique to be used in a wider range of surgeries. These devices consist of pellets of dry poly(methyl methacrylate-co-vinylpyrrolidone), compressed into discs through a hot compression moulding process. However, a number of significant problems still exist in these devices, and this thesis aims to address these issues. To date, there has been a lack of investigation of the factors governing the behaviour of anisotropic swelling. For this reason, a range of different compression ratios have been investigated, with particular focus on the relationship between the material flow during compression and the swelling behaviour of the resulting device. It was found that samples of the same initial size expand to the same reference swelling dimensions, regardless of compression ratio. During hot pressing, the material flow was found to be governed by slip-stick behaviour at the interface between the hot press and the device, affecting the properties and swelling behaviour of the devices. Based on these findings, devices were developed which could expand from a disc into a non-prismatic shape (dome or wedge). Such devices could reduce complication rates and allow the growth of new tissue with anisotropic resting tension. The devices were tested in a small in vivo trial, where it was shown that there were no adverse effects on the tissue produced, and that the shape of the expander (dome) was retained. As devices are being produced for medical use, understanding the effect of sterilization by γ-irradiation is essential, but to date this has been overlooked in the literature. It was found that γ-irradiation caused an increase in cross-linking in the P(MMA-co-NVP). Whilst this produced little change in swelling behaviour for isotropic devices, in the case of anisotropic devices it caused a change in the shape of expansion, reducing the area of new skin which could be generated by the device. It was found that by reducing the concentration of impurities (residual molecules from the polymer synthesis) the impact of γ-irradiation could be greatly reduced. Finally, controlling the rate of expansion is essential in order to avoid clinical complications. In order to control the rate of expansion, particularly during the initial period of swelling, semi-permeable PDMS coatings were applied to the compressed devices. Coatings of thickness greater than 0.375mm were found to effectively control the rate of swelling, for both cylindrical and non-prismatic shapes. As the coating thickness increased, the maximum swelling size decreased. However, it has been shown that change in height (the parameter which governs the area of skin produced) is affected less than the change in mass or diameter.

Magister Scientiae - MSc / The purpose of this research project was to assess the safety and efficacy of a combination of drugs for conscious sedation in patients undergoing office-based plastic and reconstructive surgery. A pilot study was done to determine the safety of the co-administration of the drugs used in the sedation technique. / South Africa

As more patients with large body surface area burns are surviving and requiring reconstructive surgery, there is a necessity for advances in the provision of bioengineered alternatives to autologous skin cover. The aims of this Thesis are to identify feasible source tissues of Endothelial Colony Forming Cells and Mesenchymal Stem/Stromal Cells for microvascular network formation in vitro with three-dimensional dermal substitute scaffolds. The working hypothesis is that pre-vascularised dermal scaffolds will result in better quality scarring when used with split thickness skin grafts. Human umbilical cord blood, peripheral blood and adipose tissue were collected and processed with ethical approval and informed consent. Samples were cultured to form endothelial outgrowth colonies and confluent Mesenchymal Stem/Stromal Cells, which were characterised using flow cytometry and expanded in vitro. Mesenchymal Stem/Stromal Cell multipotency was confirmed with tri-lineage mesenchymal differentiation. Primary cells were tested in a two-dimensional tubule formation co-culture assay and differences assessed using a proangiogenic antibody array. Tubule formation was tested in four different acellular dermal substitute scaffolds; Integra® Dermal Regeneration Template, Matriderm®, Neuskin-F® and De-cellularised Human Cadaveric Dermis. Umbilical cord blood was the most reliable source of Endothelial Colony Forming Cells, the yield of which could be predicted from placental weight. Microvasculature dissected free from adipose tissue was a reliable source of Mesenchymal Stem/Stromal Cells which supported significantly more tubule formation than Mesenchymal Stem/Stromal Cells from whole adipose tissue. Microvasculature Mesenchymal Stem/Stromal Cells secreted significantly higher levels of the proangiogenic hormone leptin, and addition of exogenous leptin to the tubule formation assay resulted in significantly increased tubule formation. Microvasculature was cultured in all four of the scaffolds tested, but depth of penetration was limited to 100µm. The artificial oxygen carrier perfluorocarbon was shown to increase two-dimensional tubule formation and may be useful in further three-dimensional scaffolds studies to improve microvascular penetration.

Improvements in the treatment of breast cancer have resulted in better survival rates and less breast cancer related morbidity. Nevertheless, a significant group of patients still experience a diminished quality of life as a result of lymphedema. In the early, often reversible, stage of lymphedema patients can experience subjective changes in the affected area. However, with the traditionally available tools the lymphedema often remains clinically undetectable and patients are denied essential care that can prevent worsening. Furthermore, most lymphedema assessment tools fail to support a clear unambiguous definition of lymphedema. This underlines the need for a sensitive objective measurement method that can assess lymphedema in a subclinical stage. In this study we demonstrated that measuring tissue dielectric constant (TDC) using the MoistureMeter-D is an effective method to detect tissue water changes and could potentially provide a cost-effective adequate tool to measure the early onset of breast cancer related lymphedema (BCRL). Secondarily, we established the correlation between the novel TDC method and the frequently used arm volume measurements and self-assessment questionnaires. A group of 20 female patients with clinically BCRL were included. TDC measurements in both arms and all quadrant of both breast were recorded along with volumetric measurements of both arms. All patients were asked to complete a self-report questionnaire. The novel TDC method detected significantly higher tissue water levels in the affected arm and breast compared to the control side. The TDC ratio between control and affected side showed significant correlation with self-reported pain and discomfort in both arm and breast. In the arm, the TDC method also showed correlation with the volume measurement method. The TDC value of the arm was correlated to age, but not to BMI. This study demonstrates that measuring TDC using the MMD is an effective method for quantifying lymphedema in arm and breast and is an important tool in detecting early TWC changes.

Doctor Educationis / This study was a cephalometric and dental investigation of the treatment outcomes of UCLP children treated at the Red Cross Children's Hospital (RCCH) with respect to craniofacial morphology and dental arch relationship. The quality of the outcome for the RCCH group was compared with the outcomes reported for the Six-Centre International Study (Melsted et al., 1992; Mars et al., 1992). The sample consisted of 20 (11 females, 9 males) consecutively treated UCLP children who had cephalometric and dental records taken between the ages of8 to 11years (mean 10.13 ± 1.2 years). The cephalometric analysis described by Melsted et al. (1992) was used to evaluate the skeletal and soft tissue morphology. The quality of the dental arch relationship was measured according to the Gosion Yardstick (Mars et al., 1987). The treatment outcome of children treated at the RCCH was evaluated with respect to craniofacial form and dental arch relationship. When comparing the mean cephalometric skeletal parameters of the RCCH to the six centres in the Eurocleft study, a significant difference was found between the RCCH group and centre D for most of the variables. A significant increase in the upper incisor inclination and maxillary inclination was found in the RCCH patients compared to the European centres. The difference in the soft tissue parameters was limited to the relative protrusion of the nose and the sagittal soft tissue variable sss-ns-pgs. The analysis of the Goslon scores showed a significant difference between the RCCH group and centres C, D, and F. According to the Goslon score, 85% of the RCCH patients had good to satisfactory dental arch relationship, which was comparable to that recorded for centres A(92%), B(89%) and C(94). In conclusion, the results of the cephalometric analysis and the Goslon Yardstick showed a significant difference between the RCCH group and centre D. The GosIon score indicated good quality of the dental arch relationship, which faired favourably with the better centres in the Six Centre Study.

Background and Objectives: Vascular variations appear as morphologically distinct patterns of blood diverging from the most commonly observed vessel patterns. The facial artery is considered to be the main vessel for supplying blood to the anterior part of the face. An anatomical understanding of the facial artery, its course, its topography, and its branches is important in medical and dental practice (especially in neck and face surgery), and is also essential for radiologists to be able to interpret vascular imaging in the face following angiography of the region. A profound knowledge of the arteries in the region will aid in minimizing the risks to the patient. Materials and Methods: In our publication a narrative literature review and a case report are presented. Results: A rare case of a facial artery pattern has been described anatomically for the first time with respect to its course and branching. This variation was found on the left side of a 60-year-old male corpse during anatomical dissection. The anterior branch of the facial artery arched in the direction of the labial angle, and there divided into the inferior and superior labial arteries. At the same time, the posterior branch coursed vertically and superficially to the masseter muscle. It here gave off the premasseteric branch, and continued towards the nose, where it ran below the levator labii superioris and the levator labii superioris alaeque nasi muscles and terminated at the dorsum nasi. Conclusions: Our review of the literature and the case report add to knowledge on the facial artery with respect to its topographical anatomy and its branching and termination patterns, as well as the areas of supply. An exact knowledge of individual facial artery anatomy may play an important role in the planning of flaps or tumor excisions due to the differing vascularization and can also help to prevent artery injuries during aesthetic procedures such as filler and botulinum toxin injections.

This thesis further delineates the molecular genetic basis of a relatively common craniofacial condition, coronal craniosynostosis. It used whole-exome sequencing to identify novel disease genes in patients with non-syndromic coronal synostosis and negative genetic testing. Initially, 2 patients were identified with damaging, frameshift mutations in a gene not previously linked with craniosynostosis – Transcription Factor 12 (TCF12). A further intronic mutation was identified in a third patient. This gene encodes a transcription factor that dimerises with TWIST1, mutations of which cause Saethre-Chotzen syndrome, also associated with coronal synostosis. Screening 344 undiagnosed patients identified 35 further mutations, all with coronal synostosis with 14 cases arising de novo. This work was published and testing for TCF12-related craniosynostosis was translated clinically. Significant non-penetrance (60%) was identified in mutation-positive relatives and the genetic background was investigated. Firstly, analysis of parental origins of de novo mutations identified 6 of paternal origin and helped refine haplotype assignment. Secondly, haplotype analysis of TCF12-mutation carriers revealed modest correlation with phenotypic status, but this was insufficient to be useful in clinical testing. Thirdly, TCF12 haplotypes were analysed for association with non-syndromic coronal synostosis, but no significant association was found. Further exome sequencing revealed a de novo frameshift mutation in Transcription Factor 20 (TCF20) in a patient with coronal synostosis and autism, although the mutation only correlated with the latter phenotype. Analysis of 5 trios revealed a novel variant in myosin heavy chain 4 (MYH4) in 1 family, although its role in suture development is uncertain. Reviewing pooled exome data from 19 mutation-negative patients revealed no further disease genes. In summary, this thesis describes novel gene discovery, defines a new clinical entity and investigates genetic background of penetrant and non-penetrant individuals. Further exome sequencing identified another disease gene, a de novo mutation and compiled lists of damaging variants to allow future work.