Magister Chirurgiae Dentium (MChD) / Introduction:Hereditary Epidermolysis bullosa (EB) is a group of rare mechanobullous dermatological disorders in which blisters develop following gene mutations. These genes encode structural proteins that anchor the epidermis to the underlying dermis.There are four main types of Epidermolysis bullosa, with more than 20 subtypes. The medical, physical and psychosocial aspects of Epidermolysis bullosa are well documented (Lucky et al, 2005; Mellerio et al, 2005). Many studies have documented case reports of associated oral lesions (Silva et al, 2004; Pacheco and de Sousa Araugio 2008; Siqueira et al, 2008). However, no assessment of the impact of these oral lesions on the affected person's everyday life has been made. The morbidity of the oral lesions associated with EB is expected to have an impact on the quality of life of these patients.Aim:To assess the prevalence and impact of oral lesions on daily activities in persons with Epidermolysis bullosa in Cape Town, South Africa, utilizing the Oral Impact on Daily Performance (OIDP) measure. Research Design and Methodology A case-controlled, descriptive analysis of the way in which oral lesions impact on quality of life in persons with Epidermolysis bullosa was carried out using semi-structured interviews. Fourteen persons with a confirmed diagnosis of hereditary Epidermolysis bullosa who attended the dermatology clinics at the Red Cross and Groote Schuur hospitals participated in the study. The control group comprised eighteen persons closely matched for gender, age, and dental status. Three persons with EB were unavailable for inclusion in the study.Results and Discussion Fourteen persons with Epidermolysis bullosa and eighteen controls were included in the study. Epidermolysis bullosa Simplex comprised the largest sub-group (n=9). Two persons had Junctional Epidermolysis bullosa, two had recessive Dystrophic Epidermolysis bullosa and one person had Kindler syndrome. The oral manifestations observed were consistent with those reported in the literature(Chimenos et al, 2003; Silva et al, 2004; Pekinar et al, 2005). No significant oral lesions (other than tooth decay) were seen in persons in the Epidermolysis bullosa Simplex group. Oral ulcers, atrophy of the dorsal surface of the tongue and gingival erythema were seen in persons with Junctional Epidermolysis Bullosa. The two individuals with Dystrophic Epidermolysis bullosa had a maximal oral opening of 15mm and 24mm. Ankyloglossia, depapillation of the dorsal tongue, absence of palatal rugae and poor oral hygiene was seen in these two persons. The patient with Kindler syndrome presented with erythematous and inflamed gingiva and cratering in the maxillary anterior interdental area. The gingiva appeared desquamative, fragile and bled with even the slightest provocation. Healing peri-oral blisters and angular cheilitis was also seen. His mouth opening was restricted to a maximal oral aperture of 13mm and his tongue extrusion was limited to only the tip of the tongue passing over the lower anterior incisor teeth.Defects in the tooth enamel was recorded in both participants with Junctional Epidermolysis bullosa and one person with dystrophic Epidermolysis bullosa, as well as excessive occlussal tooth wear (attrition), which may have been secondary to enamel hypoplasia. The dental caries status of the Epidermolysis bullosa and control groups varied according to age. The dmf for persons with Epidermolysis bullosa (all of whom had Epidermolysis bullosa Simplex), was lower than in the control group. The DMF in EB persons (15.3) was higher than in the control group (10.1).Toothache and tooth decay were the most common perceived complaints in both the Epidermolysis bullosa and control participants, accounting for the high overall OIDP score in both groups (87.5%). No statistically significant difference was found between the two groups (85.7% and 88.9% for Epidermolysis bullosa and control group persons respectively).Conclusion:The results of the study show that oral lesions (particularly tooth decay and toothache) in persons with Epidermolysis bullosa do affect their daily activities and the impact thereof is high. Other oral manifestations, irrespective of the subtype, had little impact on the OIDP score. This may be because the EB persons become tolerant of and “learn to cope” with them.Recommendations:Epidermolysis bullosa is a rare condition and not all persons with EB will present with lesions. However, all health personnel (including oral health profession) must be cognizant of this condition, in order to manage these persons safely, without incurring harm inadvertently. Thus, the overall management of persons with Epidermolysis bullosa must encompass ways to minimize and prevent trauma; provide an optimum wound healing environment; provide pain management and judicious checks for the development of premalignant lesions. This necessitates a multidisciplinary and holistic approach, with emphasis on patient involvement. To this end, an oral health care programme should form an integral part of their management because of the risk of dental disease. Periodic recall visits will enable the monitoring of home care and minimize the need for advanced restorative procedures. In this way, one may reduce the impact any oral problems may have, so that they do not further influence the patients well being.

Trials were performed in sheep and rats to elucidate the pathogenesis of the myocardial lesions in gousiekte. In the first trial the macro- and lightmicroscopical lesions and myofibre morphometrical changes were studied in ten sheep exposed daily to Pachystigma pygmaeum at 10 g/kg live body weight for 23 to 31 days. All the treated animals either died or were euthanased in extremis between 31 and 51 days after the commencement of dosing. In the second trial the myocardial ultrastructural lesions were studied in six sheep dosed with Fadogia homblei at a dosage rate of 10 g/kg per day live body weight for 22 to 23 days. All the treated animals either died or were euthanased in extremis between 34 and 57 days after the commencement of dosing. The main objective of the third trial was to compare the myocardial lesions in rats exposed to pavetamine with lesions recorded in sheep exposed to P. pygmaeum and F. homblei plant material. Seven rats were injected intraperitoneally with pavetamine at a dosage rate of 5 mg/kg on day 0 and three were killed on day 6. The remaining four were injected with a second dose of pavetamine at a dosage rate of 3 mg/kg on day 27 and euthanased on day 42. In the sheep exposed to P. pygmaeum pulmonary oedema and hydropericardium were present in eight, hydrothorax in four and ascites in two cases. In two sheep cardiac dilatation was associated with subendocardial pallor (fibrosis) and transmural myocardial mottling. Myofibre hypertrophy was recorded in all the sheep, myofibre necrosis and replacement fibrosis occurred in seven animals the latter being particularly evident in animals with medium to long latent periods. A mononuclear cellular infiltration that varied from mild to severe was evident in all the cases and endocardial thickening, which is an indication of cardiac dilatation, was present in seven animals. Myofibre atrophy occurred in eight animals and was the most striking lesion in a sheep with a short latent period. “Typical” gousiekte lesions, characterised by myofibre necrosis and atrophy, replacement fibrosis and an associated round cell infiltration in the subendocardial region, were present in eight of the sheep. “Atypical” lesions, characterised by hypertrophy of myofibres with multifocal coagulative necrosis or myofibre atrophy, were recorded in two sheep, both of which had short latent periods. The myofibre diameter and nuclear area in the affected animals differed statistically from those of the controls (larger) and anisocytosis and anisonucleosis were particularly striking in sheep with intermediate to long latent periods. The most striking ultrastructural lesions included breakdown of myofibrils, involving in particular what appeared to be thick (myosin) filaments; selective proliferation of organelles such as mitochondria and sarcoplasmic reticulum in areas previously occupied by myofibrils; excessive folding of the myofibre sarcolemma; and advanced myocardial injury characterised by complete loss of myofibrils with loss of intercellular connections and necrosis of myocardial cells. No lesions were present in the rats exposed to a single dose of pavetamine, although they became anorexic and lost weight. Rats exposed to pavetamine twice became anorexic within two to three days after the first exposure and regained weight within a few days (on about day 7). However, they kept on losing weight after the second exposure and continued to do so until termination of the experiment. As a general rule the myocardial lesions were mild in the rats dosed twice with pavetamine. Transmural multifocal myocardial necrosis, with an associated round cell infiltration and replacement fibrosis, was the most striking light- microscopical lesion. The lesions were comparable with “atypical” lesions in ruminants. Ultrastructural lesions in degenerative/necrotic fibres included karyolysis, swelling of the mitochondria and focal lysis of myofilaments. In rats exposed to pavetamine twice there was statistical evidence of myofibre atrophy. Based on the information emanating from this study and previous research the following deductions are made to explain the pathogenesis of the myocardial lesions: 1. Pavetamine has a prolonged effect on the myocardium owing to inhibition of protein synthesis, and also influences the energy production system, which affects the function of myocytes. The structure of the myocytes is not affected during the early stages of the latent period but eventually myofibre hypertrophy, atrophy, degeneration and necrosis are seen. 2. Replacement fibrosis in the subendocardial region is a sequel to the effect of pavetamine on myofibres and the consequence of ischaemia owing to impaired myocardial perfusion of, particularly, the subendocardial region, as a result of decreased myocardial contraction, increased diastolic pressure, tachycardia and myofibre hypertrophy. 3. Cardiac dilatation is a compensatory mechanism, a result of the myofibre damage inflicted by pavetamine and ischaemia (pathological dilatation). 4. Lesions in animals with gousiekte represent a final common pathway of cellular damage rather than a manifestation of a specific type of heart disease. Animals may die during any stage in the development of the lesions. “Atypical” lesions represent a manifestation of the disease in a progression that terminates with dilated cardiomyopathy if the animal does not die during the early stages. These deductions provide an explanation, for the first time, for the latent period between ingestion of the plant and the onset of illness in gousiekte. They also explain the wide range of lesions seen in experimental cases. It furthermore demonstrate that the “typical” lesions of gousiekte are not pathognomonic, and that the absence of “typical” lesions does not rule out a diagnosis of gousiekte in situations where exposure to the causative plants and the clinical history support such a diagnosis. / Thesis (PhD)--University of Pretoria, 2008. / Paraclinical Sciences / unrestricted

No / In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not only psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/tumor necrosis factor-α (TNFα)-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses, IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, because of its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.

No description available.

Atherosclerotic and restenotic lesions develop as a result of an excess inflammatory response to vascular injury. Glucocorticoid hormones have widely-recognised anti-inflammatory and anti-proliferative properties which appear to make them ideal candidates for inhibition of vascular lesion development. Indeed, administration of glucocorticoids to experimental animals does inhibit the growth of vascular lesions in some models. In addition, glucocorticoids are currently being trialled clinically as anti-restenotic agents. However, glucocorticoid excess in patients, either as a result of Cushing’s syndrome or chronic steroid therapy, is associated with enhanced CVD risk. Therefore, the effects of glucocorticoids on vascular lesion development remain imperfectly understood. The overall objective of these studies was to explore the influence of endogenous and exogenous glucocorticoids on vascular lesion development using murine models of atherosclerosis (ApoE-/- mice fed a “western” diet) and neointimal hyperplasia (wireinduced femoral artery injury). The work described in this thesis addresses the hypothesis that glucocorticoids are pro-atherogenic, yet anti-restenotic. Mice were bilaterally adrenalectomised to investigate the role of endogenous glucocorticoids on vascular lesion development. Removal of the adrenal glands had no influence on atherogenesis or neointima development. The influence of exogenous glucocorticoids on lesion development was assessed by orally administering dexamethasone (0.1 or 0.8mg/kg/day). Atherosclerotic lesion burden was augmented by dexamethasone administration. Conversely, fibro-proliferative neointimal proliferation was inhibited by dexamethasone. However, this effect was obscured by thrombotic lesion development. It was proposed that this thrombotic effect is attributable to increased plasminogen activator inhibitor-1 (PAI-1), which was tested using PAI-1 deficient mice. Although PAI-1 was found to mediate the systemic pro-thrombotic effect of dexamethasone, it is not required for the enhanced development of thrombotic lesions at the site of intra-luminal injury. These results suggest that physiological levels of endogenous glucocorticoids play a limited role in vascular lesion development. Conversely, although exogenous glucocorticoids inhibit fibro-proliferative intimal hyperplasia, they appear to have significant detrimental influences on lesion development, augmenting atherosclerosis and inducing thrombotic neointimal lesion formation following vascular injury. Further research is therefore required to improve the cardiovascular outcome of patients requiring glucocorticoid therapy and for the use of glucocorticoids as antirestenotic agents.

Os objetivos deste estudo foram desenvolver e testar in vivo e in vitro um método de detecção de lesões de cárie utilizando um espectrômetro portátil (EP); analisar o desempenho do EP e do equipamento comercial DIAGNOdent (Dd); correlacioná-los entre si, assim como com o padrão ouro, a área de secção e a profundidade das lesões. Os 66 sítios oclusais de pré-molares foram analisados in vivo com o Dd e, em seguida, a fluorescência induzida por um laser diodo (lexc ~ 657nm) foi coletada por fibra óptica, conduzida ao EP e analisada sob a forma de espectros, os quais foram normalizados e para os quais foi calculada a razão da área sob a curva dos espectros cariado e sadio (RACE). Os experimentos foram conduzidos in vitro nos mesmos sítios. O padrão ouro foi obtido por meio de microscopia de luz polarizada. Utilizou-se o índice de correlação linear de Pearson para comparar o Dd e o EP entre si e com a profundidade e área das lesões. A área sob a curva ROC, a sensibilidade, a especificidade e a acurácia foram calculadas e comparadas com o teste de McNemar. O Dd e a RACE apresentaram correlação significante com o padrão ouro (p < 0,01 para Dd e p < 0,05 para RACE) e entre si (r = 0,83 in vivo e r = 0,87 in vitro). Os equipamentos apresentaram baixa correlação, porém significante, com a profundidade das lesões tanto in vivo quanto in vitro (r = ~ 0,43). A área de secção transversal da lesão não influenciou nas medidas obtidas com o Dd e o EP. O Dd apresentou maior sensibilidade (0,76) do que o EP (0,60) in vivo (p < 0,05), embora isto não tenha aumentado o seu desempenho. In vitro, o EP apresentou maior sensibilidade (0,88) do que o Dd (0,79), mas essa diferença não foi significante. Os outros parâmetros também não apresentaram diferenças estatisticamente significantes (p < 0,05). O EP apresentou correlação positiva com o Dd, igual correlação com a profundidade da lesão e maior capacidade para detectar o tecido cariado in vitro, em relação ao Dd, o que sugere que com ponta convergente e angulada e software dedicado, o método será promissor para utilização em clínicas odontológicas em um futuro próximo. / The aims of this study were to develop and test a method to detect caries lesions in vivo and in vitro, using a portable spectrometer (PS); to analyze the performance of PS as well as the commercial device DIAGNOdent (Dd); correlate them with the gold standard, their tranversal section areas and lesions depth and between themselves. 66 occlusal pre-molars sites were examined in vivo with Dd. Sequentially, fluorescence (lexc ~ 657nm) was collected by an optical fiber, conducted to PS and then analyzed as spectra, which were normalized and had calculated the Ratios of their Areas Under the Curves (RAUC) of carious and sound tissues. Experiments were conducted in vitro in the same sites. Gold Standard was obtained by polarized light microscopy. Pearson correlation was used to compare the devices with transversal section area, lesions depth and between themselves. The area under ROC curve, sensitivity, specificity as well as accuracy were calculated and verified with McNemar test. Dd and RAUC showed statistically significant correlation with gold standard (p < 0.01 for Dd and p < 0.05 for RAUC) and between themselves (r = 0,83 in vivo and r = 0,87 in vitro). Although it was significant, the devices showed low correlation with depth of lesions in vivo and in vitro (r = ~ 0.43). The transversal section area of the lesion had no influence on readings in both devices. Dd showed higher sensitivity (0.76) than PS (0.60) in vivo (p < 0.05), though this fact was not able to improve its performance. In turn, PS showed higher sensitivity (0.88) than Dd (0.79) in vitro, but this difference was not significantly. The other parameters did not show statistically significant differences (p < 0.05) between methods. PS showed positive correlation with Dd, equal correlation with lesions depth and higher ability of detecting the disease in vitro, what suggests that if accompanied with a conic and an angulated probe and a dedicated software, the PS method could be useful in clinics in the near future.

Os objetivos deste estudo foram desenvolver e testar in vivo e in vitro um método de detecção de lesões de cárie utilizando um espectrômetro portátil (EP); analisar o desempenho do EP e do equipamento comercial DIAGNOdent (Dd); correlacioná-los entre si, assim como com o padrão ouro, a área de secção e a profundidade das lesões. Os 66 sítios oclusais de pré-molares foram analisados in vivo com o Dd e, em seguida, a fluorescência induzida por um laser diodo (lexc ~ 657nm) foi coletada por fibra óptica, conduzida ao EP e analisada sob a forma de espectros, os quais foram normalizados e para os quais foi calculada a razão da área sob a curva dos espectros cariado e sadio (RACE). Os experimentos foram conduzidos in vitro nos mesmos sítios. O padrão ouro foi obtido por meio de microscopia de luz polarizada. Utilizou-se o índice de correlação linear de Pearson para comparar o Dd e o EP entre si e com a profundidade e área das lesões. A área sob a curva ROC, a sensibilidade, a especificidade e a acurácia foram calculadas e comparadas com o teste de McNemar. O Dd e a RACE apresentaram correlação significante com o padrão ouro (p < 0,01 para Dd e p < 0,05 para RACE) e entre si (r = 0,83 in vivo e r = 0,87 in vitro). Os equipamentos apresentaram baixa correlação, porém significante, com a profundidade das lesões tanto in vivo quanto in vitro (r = ~ 0,43). A área de secção transversal da lesão não influenciou nas medidas obtidas com o Dd e o EP. O Dd apresentou maior sensibilidade (0,76) do que o EP (0,60) in vivo (p < 0,05), embora isto não tenha aumentado o seu desempenho. In vitro, o EP apresentou maior sensibilidade (0,88) do que o Dd (0,79), mas essa diferença não foi significante. Os outros parâmetros também não apresentaram diferenças estatisticamente significantes (p < 0,05). O EP apresentou correlação positiva com o Dd, igual correlação com a profundidade da lesão e maior capacidade para detectar o tecido cariado in vitro, em relação ao Dd, o que sugere que com ponta convergente e angulada e software dedicado, o método será promissor para utilização em clínicas odontológicas em um futuro próximo. / The aims of this study were to develop and test a method to detect caries lesions in vivo and in vitro, using a portable spectrometer (PS); to analyze the performance of PS as well as the commercial device DIAGNOdent (Dd); correlate them with the gold standard, their tranversal section areas and lesions depth and between themselves. 66 occlusal pre-molars sites were examined in vivo with Dd. Sequentially, fluorescence (lexc ~ 657nm) was collected by an optical fiber, conducted to PS and then analyzed as spectra, which were normalized and had calculated the Ratios of their Areas Under the Curves (RAUC) of carious and sound tissues. Experiments were conducted in vitro in the same sites. Gold Standard was obtained by polarized light microscopy. Pearson correlation was used to compare the devices with transversal section area, lesions depth and between themselves. The area under ROC curve, sensitivity, specificity as well as accuracy were calculated and verified with McNemar test. Dd and RAUC showed statistically significant correlation with gold standard (p < 0.01 for Dd and p < 0.05 for RAUC) and between themselves (r = 0,83 in vivo and r = 0,87 in vitro). Although it was significant, the devices showed low correlation with depth of lesions in vivo and in vitro (r = ~ 0.43). The transversal section area of the lesion had no influence on readings in both devices. Dd showed higher sensitivity (0.76) than PS (0.60) in vivo (p < 0.05), though this fact was not able to improve its performance. In turn, PS showed higher sensitivity (0.88) than Dd (0.79) in vitro, but this difference was not significantly. The other parameters did not show statistically significant differences (p < 0.05) between methods. PS showed positive correlation with Dd, equal correlation with lesions depth and higher ability of detecting the disease in vitro, what suggests that if accompanied with a conic and an angulated probe and a dedicated software, the PS method could be useful in clinics in the near future.

No description available.

No description available.

The reported prevalence of decalcification in orthodontic patients varies from 2 to 96% mainly due to the lack of a standard examination technique. The aims of this study were: 1) to determine the prevalence of white spot lesions around brackets using visual examination and the DIAGNOdent; 2) to determine which teeth were the most susceptible to decalcification; and 3) to test the accuracy of the DIAGNOdent by comparing to the visual examination. The presence of white spot lesions was determined in two groups of patients who were 6 and 12 months into orthodontic treatment, respectively. The control group consisted of patients who were examined for white spot lesions immediately after having their braces placed on their teeth. The prevalence of white spot lesions was 38%, 46%, and 11% for the 6-month, 12-month, and control groups, respectively. There was a statistically significant correlation (r = 0.71) between the DIAGNOdent measurements and the visual examination.