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Post-transplant malignancies cause significant morbidity and mortality. In this thesis we investigated malignancies in renal transplanted patients from a clinical viewpoint. The use of regional tumour registries considerably improved identification of pre- and post-transplant malignancies, which are generally underreported in transplant registries. Despite previously adequate cancer treatments with favourable prognosis, patients with pre-transplant malignancies showed higher incidence of post-transplant cancer and reduced survival compared to a 1:3 ratio matched control group of patients without a previous cancer from the Collaborative Transplant Study in Europe. A careful oncological surveillance pre-transplant and post-transplant is recommended. A multidisciplinary team evaluated the immunosuppressive and oncological treatment in a clinical prospective observational study of 120 renal transplanted patients with post-transplant malignancies. In two-thirds of the patients immunosuppression was possible to change to mTOR inhibitors with anti-tumour effects. Oncological treatment was adjusted in 50% of patients with solid or haematological tumours. MDT assessments are essential for optimizing treatment of post-transplant malignancies. Number of previous cutaneous squamous cell carcinoma (SCC) posed the most significant risk variable in predicting subsequent SCCs during a two-years study of 73 transplanted patients with at least one SCC. Incidence of transplant-derived tumours is 5 times higher than anticipated. Three of eleven cancers in urinary tract and two of four cancers in the transplants were transplant-derived. Five of eleven cancers of the urinary tract were BK-virus positive. Allograft immune response against these tumours offer new options for cancer treatment such as immunomodulatory or anti-viral treatment in combination with modified immunosuppression.

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Malignant hyperthermia (MH) is an autosomal dominant pharmacogenetic disorder (Deufel et aI., 1992). It is potentially fatal and one of the leading causes of death due to anaesthesia. An MH episode is triggered when MH susceptible individuals are exposed to certain inhalation anaesthetic agents and depolarising skeletal muscle relaxants (Maclennan, 1992). To date, twenty-three mutations have been reported in the skeletal muscle ryanodine receptor gene (RYR1), located on chromosome 19q13.1, and twenty-two of these mutations have been associated with MH (Brandt et aI., 1999). The 1403M mutation has only been associated with central core disease (CCD). CCD and MH are phenotypically distinct allelic variants as mutations in the same gene are responsible for both these disorders (Quane et al., 1993). Seventeen MH families, four South African and thirteen North American families, were included in this study. DNA from selected MH individuals were screened for nine of the reported mutations (Cys35Arg, Arg163Cys, Gly248Arg, Gly341Arg, lIe403Met, Tyr522Ser, Arg614Cys, Gly2435Arg and Arg2436His). The interaction between polymorph isms and mutations, which might modify or contribute to the MH phenotype, is currently still unknown. For this reason the DNA from selected individuals were screened for the presence of all of the nine mutations investigated in this study. Two mutations, Arg614Cys and Gly2435Arg, were observed in the group of MH families included in this study. The Arg614Cys mutation was identified in a large South African MH family (MH105). A total of 39 individuals of South African family MH105 were subsequently screened for the presence of this mutation. Twelve individuals, three of whom have not been tested via the in vitro contracture test (IVCT), were positive for the mutation. Two individuals from this family displayed phenotype-genotype discordance. The Gly2435Arg mutation was identified in a North American MH family (US2). This small family of five individuals included three individuals diagnosed via the North American IVCT protocol. The three phenotyped individuals included two MH positive and one MH negative individual. The Gly2435Arg mutation segregated with the MH phenotype observed in this North American family. This is the first report of the Gly2435Arg mutation in the North American MH population. The identification of the Arg614Cys and Gly2435Arg mutations contributed towards establishing a molecular diagnostic service for individuals within these particular MH families. None of the other seven mutations investigated were detected in the group of families included in this study. The DNA alterations are therefore not present as polymorphisms in these families, and can thus not contribute to the MH phenotype segregating in any of the families. If the families investigated in this study are truly representative of the South African and North American populations it is possible that these seven mutations are absent in these two populations. These mutations might, therefore, be population specific or even family specific. / Dissertation (MSc)--University of Pretoria, 2010. / Genetics / unrestricted

Malignant hyperthermia (MH) is a rare but severe reaction that can occur in the operating room. Due to the low volume of these reactions, nurses are often unprepared to handle the event; however, not recognizing the event and intervening can lead to the death of the patient. This is a practice problem that can be addressed through a nursing staff education simulation training program. The purpose for this doctoral project was to develop a multidisciplinary MH simulation program that could improve nursing knowledge when caring for patients experiencing an MH crisis in the operating room. The practice-focused question for this project asked whether MH multidisciplinary simulation education improves the knowledge of nurses in the operating room setting. Utilizing Kolb’s theory of experiential learning, nurses were developed through the four stages of learning. Sources of evidence for this project included a review of the literature. Data were also collected pre- and post-intervention on the reliability of simulation training to improve operating room nurses’ knowledge of caring for the patient experiencing an MH crisis. Descriptive statistics via percent difference evaluated pre- and post-test evaluations. Results revealed a 16.4% increase knowledge scores from pretest to posttest following participation in the MH simulation. Improving patient outcomes creates significant social impact by developing community confidence in the surgical care provided by local hospitals.

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