No description available.

No description available.

No description available.

No description available.

No description available.

Oral squamous cell carcinoma (SCC) is a lethal, deforming disease of global significance and rising incidence. In 2011, 6,767 new cases and 2,056 deaths occurred in the UK. Cancers are preceded by oral potentially malignant disorders (PMD), recognizable mucosal diseases harbouring significantly increased risk of carcinoma. These manifestations offer clinicians a ‘therapeutic window’ to intervene during carcinogenesis, although contemporary practice remains unable to predict individual lesion behaviour or quantify risk for malignant transformation. No clear management guidelines exist and available scientific literature is unable to answer the fundamental question whether intervention prevents cancer. This MD thesis includes 7 published papers on oral pre-cancer and 4 observational studies from a specialist PMD service coordinated by the author in Newcastle upon Tyne in Northern England. PMD management involves a complex interaction between patients, clinicians’ views on diagnosis and treatment and histopathological assessment of mucosal biopsy specimens. Uncertainty regarding the ‘potentially malignant state’ remains a pernicious influence throughout. Newcastle PMD patients were profiled as predominantly male, with a median age of 60yrs, and regular users of both tobacco and alcohol. Most presented with single-site disease, primarily leukoplakia on the floor of mouth and ventro-lateral tongue, with over 80% exhibiting epithelial dysplasia on histopathological examination. Approximately 70% underwent interventional therapy using CO2 laser surgery. 840 laser treatments were performed between 1996 and 2015 and the efficacy of laser intervention was examined by reviewing clinico-pathological details and clinical outcome for 590 PMD patients followed for a mean of 7.3yrs. Histopathology required ‘up-grading’ in 36% following definitive examination of laser excision specimens. 74.2% of patients were disease free, primarily younger patients with ‘low-grade’ dysplasia, 9% exhibited persistent disease and were older with gingival lesions often proliferative verrucous leukoplakia (PVL). In 12%, unexpected SCC was identified on excision, whilst 4.8% transformed to malignancy. Interventional laser surgery facilitates definitive diagnosis and efficacious treatment, allows early diagnosis and treatment of SCC, identifies patients at risk of progressive disease and defines clinical outcome categories. Evidence is lacking, however, that intervention halts the progress of carcinogenesis. Multi-centre, prospective, randomized, controlled trials are needed to confirm the efficacy of interventional surgery, to characterise PMD natural history and to disseminate research findings. It is hoped that the clinical work presented in this MD thesis will inform and encourage further research into PMD and lead to a reduction in the incidence of malignancy and improved morbidity and mortality.

Cytogenetic analysis of the malignant clone is clinically important in haematological malignancy. Analysis by metaphase cytogenetics is restricted to the small proportion of malignant cells which are actively dividing. This thesis explores the dynamics of malignant clones using the technique of fluorescence in situ hybridization (FISH) to visualize chromosomal abnormalities in interphase (non-dividing) cells. Hyperdiploid (>46 chromosomes) clones have been investigated by interphase FISH in acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) using appropriate chromosome-specific probes. A hyperdiploid clone was detected in interphase cells in 9/65 patients with ALL in whom metaphase cytogenetics had failed or was normal. A single hyperdiploid cell was identified as clonal in one patient with MDS but not in six others with AML, MDS or ALL. The involvement of different cell lineages in the malignant clone was investigated by simultaneous FISH and identification of the cell type by morphology or monoclonal antibodies. In ALL, hyperdiploid clones were restricted to the lymphoid blasts in 9/9 cases, while Philadelphia (Ph) positive clones, (identified by probes to the genes m- BCR or M-BCR and ABL which fuse as a result of the translocation) were found either in lymphoid blasts alone (1/3 cases) or in both lymphoid and myeloid cells (2/3 cases). In AML trisomy 8 (using a chromosome 8-specific probe) and an 11q23 abnormality (which split YAC 13HH4) were both found only in the myeloid blasts, in 3/3 and 2/2 cases respectively. A sensitive method for the detection of hyperdiploid \geq 50 clones in ALL was developed for minimal residual disease detection. Simultaneous probing of three chromosomes enabled detection of one hyperdiploid cell in 10,000. Heterogeneity in the speed with which the clone was eliminated in remission was seen in 16 patients and early relapse was detected in one patient.

No description available.

No abstract available. Copyright / Dissertation (MChD)--University of Pretoria, 2010. / Oral Pathology and Oral Biology / unrestricted

The syndrome of Malignant Hyperpyrexia in man follows administration of certain general anaesthetic agents, and, although rare, is fatal in 70% of cases (EDITORIAL, 1968). Following exposure to the anaesthetic, there is, in most instances of susceptible individuals, a rapid rise in body temperature, usually within a period of 10 minutes, often accompanied by muscular rigidity of the limbs~ Sometimes hyperthermia has.been delayed for hours and muscular rigidity not pronounced. The temperature reached maybe 43°C (115°F) or even somewhat above this. Halothane, CF3CHBrCl, a ha../o/~nated hydrocarbon, is thought to be responsible for most cases(WILSON, NICHOLS, DENT and ALLEN, 1966). Succinyl choline lfH2COOCH2CH2*(cH3 )~ 201_~H2COOCH2CH2~(cH3 )3 a skeletal muscle relaxant employed during anaesthesia, has also been implicated (BRITT and KALOW, 1970; HARRISON, 1971).