A osteoporose é uma doença óssea metabólica que afeta também os ossos dos maxilares. Causa um aumento da porosidade que reflete na integração da qualidade e densidade óssea mineral, prejudicando o tratamento reabilitador com implantes. O meio diagnóstico padrão ouro é densitometria óssea por emissão dupla de raios X(DXA), mas a tomografia computadorizada também se mostra muito eficaz na avaliação da qualidade óssea através da escala Hounsfield. Nesse estudo, avaliamos as densidades ósseas das cabeças mandibulares, regiões dos dentes 13,23 na maxila, 36,46 na mandíbula e vértebras cervicais C1, C2, C3, através da escala Hounsfield em exames tomográficos, e correlacionamos seus valores para diagnóstico de Osteoporose localizada ou sistêmica. Avaliamos 79 TC multi-slice de pacientes que realizaram exames simultaneamente da maxila e da mandíbula,sendo que 35 homens e 44 mulheres com mais de 40 anos de idade. Usamos o software e-film para analise das regiões estudadas. Os resultados mostram que 59.96% apresentam densidade abaixo de 200 HU em mais de 03 sítios estudados, classificando-os como osteoporose sistêmica, e 43.03% apresentam osteoporose localizada. No sexo feminino 61.76% apresentam osteoporose localizada e 60% osteoporose sistêmica. Já o sexo masculino 38.23% apresenta osteoporose localizada e 40% apresenta osteoporose sistêmica. Pudemos conclui que a tomografia computadorizada multislice obtida para finalidade de diagnóstico em odontologia mostrou-se capaz de identificar indivíduos com risco de osteoporose sistêmica, considerando a metodologia aplicada a esta amostragem. / Osteoporosis is a metabolic bone disease that also affects the bones of the jaws. Causes an increase in porosity that reflects the integration of quality and bone mineral density, hindering rehabilitation treatment with implants. The gold standard diagnostic tool is bone densitometry by dual energy x-ray absorptiometry (DXA), computed tomography but also proves very effective in assessing bone quality through Hounsfield scale. In this study, we evaluated the bone density of mandibular heads, regions of the teeth in the maxilla 13,23, 36.46 mandible and cervical vertebrae C1, C2, C3, through Hounsfield scale CT scans, and correlated their values for diagnosis of Osteoporosis localized or systemic. We evaluated 79 multi-slice CT of patients who underwent both examinations of the maxilla and mandible, with 35 men and 44 women over 40 years of age. We use software to analyze and Efilm-investigated regions. The results show that 56.06% have density below 200 HU from over 03 sites studied, classifying them as systemic osteoporosis, and 43.03% have localized osteoporosis. In females 61.76% have localized osteoporosis and 60% systemic osteoporosis. Have the male presents 38.23% localized osteoporosis and 40% presents systemic osteoporosis. We concluded that multislice computed tomography obtained for diagnostic purposes in dentistry proved to be able to identify individuals at risk for systemic osteoporosis, considering the methodology applied to this sample.

A osteoporose é uma doença óssea metabólica que afeta também os ossos dos maxilares. Causa um aumento da porosidade que reflete na integração da qualidade e densidade óssea mineral, prejudicando o tratamento reabilitador com implantes. O meio diagnóstico padrão ouro é densitometria óssea por emissão dupla de raios X(DXA), mas a tomografia computadorizada também se mostra muito eficaz na avaliação da qualidade óssea através da escala Hounsfield. Nesse estudo, avaliamos as densidades ósseas das cabeças mandibulares, regiões dos dentes 13,23 na maxila, 36,46 na mandíbula e vértebras cervicais C1, C2, C3, através da escala Hounsfield em exames tomográficos, e correlacionamos seus valores para diagnóstico de Osteoporose localizada ou sistêmica. Avaliamos 79 TC multi-slice de pacientes que realizaram exames simultaneamente da maxila e da mandíbula,sendo que 35 homens e 44 mulheres com mais de 40 anos de idade. Usamos o software e-film para analise das regiões estudadas. Os resultados mostram que 59.96% apresentam densidade abaixo de 200 HU em mais de 03 sítios estudados, classificando-os como osteoporose sistêmica, e 43.03% apresentam osteoporose localizada. No sexo feminino 61.76% apresentam osteoporose localizada e 60% osteoporose sistêmica. Já o sexo masculino 38.23% apresenta osteoporose localizada e 40% apresenta osteoporose sistêmica. Pudemos conclui que a tomografia computadorizada multislice obtida para finalidade de diagnóstico em odontologia mostrou-se capaz de identificar indivíduos com risco de osteoporose sistêmica, considerando a metodologia aplicada a esta amostragem. / Osteoporosis is a metabolic bone disease that also affects the bones of the jaws. Causes an increase in porosity that reflects the integration of quality and bone mineral density, hindering rehabilitation treatment with implants. The gold standard diagnostic tool is bone densitometry by dual energy x-ray absorptiometry (DXA), computed tomography but also proves very effective in assessing bone quality through Hounsfield scale. In this study, we evaluated the bone density of mandibular heads, regions of the teeth in the maxilla 13,23, 36.46 mandible and cervical vertebrae C1, C2, C3, through Hounsfield scale CT scans, and correlated their values for diagnosis of Osteoporosis localized or systemic. We evaluated 79 multi-slice CT of patients who underwent both examinations of the maxilla and mandible, with 35 men and 44 women over 40 years of age. We use software to analyze and Efilm-investigated regions. The results show that 56.06% have density below 200 HU from over 03 sites studied, classifying them as systemic osteoporosis, and 43.03% have localized osteoporosis. In females 61.76% have localized osteoporosis and 60% systemic osteoporosis. Have the male presents 38.23% localized osteoporosis and 40% presents systemic osteoporosis. We concluded that multislice computed tomography obtained for diagnostic purposes in dentistry proved to be able to identify individuals at risk for systemic osteoporosis, considering the methodology applied to this sample.

Background: Registering a true maximum bite force on the most commonly-used force transducers is problematic. It is often believed that this is related mainly to discomfort and the fear of breaking teeth. Objectives: The aim of the project was to compare the suitability of different bite force measuring transducers including ones which were designed to improve subject comfort. The transducers used were a traditional strain-gauge transducer with and without covering with ethylene vinyl acetate (EVA) sheets, and a newly-developed pressure transducer. Methods: Five separate studies were performed in this project. The experiments were carried out on human volunteer subjects (aged 24 to 41 years). They were all dentate with no missing anterior teeth and with no crowns on these teeth. The following procedures were used in some or all of the studies: measurement of MVBF, electrical stimulation of the masseter muscle, and EMG recording from two pairs of jaw closing muscles. Results: The highest MVBF values were recorded on the pressure transducer, mean (± S.D.) 464 N ± 224 N; followed by the strain-gauge transducer with EVA sheets, 243 ± 80 N; and last of all the strain-gauge transducer with silicone indices, 165 ± 35 N; or acrylic indices, 163 ± 82 N. Significantly higher maximum potential bite forces were predicted by twitch interpolation for the pressure transducer (730 ± 199 N) than for the strain-gauge transducer with EVA sheets, 354 ± 67 N (Paired t test, P < 0.05). Significantly higher EMGs of the masseter and anterior temporalis muscles were found to be associated with MVBFs on the pressure transducer than with MVBFs on the strain-gauge transducer with EVA sheets (Paired t test, P < 0.05). Conclusions: It is concluded that: a) the pressure transducer system and to a lesser extent the strain-gauge transducer covered with EVA sheets seemed to overcome the fear associated with biting on the hard surfaces of the strain-gauge transducer alone; b) the pressure transducer may have some multi-directional capabilities which allow for total bite forces, or at least larger parts of them, to be recorded than on a uni-directional strain-gauge transducer.

Os bisfosfonatos (BF) são amplamente utilizados no tratamento de doenças osteolíticas como metástases ósseas e osteoporose. A osteonecrose dos maxilares associada ao uso de BF (OMAB) é caracterizada pela presença de osso exposto ou que pode ser sondado através de uma fístula que persiste por mais de oito semanas em pacientes com história de terapia de BF e sem história de radioterapia na região de cabeça e pescoço e/ou sem doença metastática nos maxilares. A incidência de OMAB aumenta com a potência, duração do tratamento e dose de BF recebida. Até o presente momento, a fisiopatologia da OMAB não está clara, dificultando a prevenção e o tratamento. O objetivo deste estudo foi avaliar o efeito da administração de altas doses Ácido Zoledrônico (AZ) por período prolongado no osso esponjoso da mandíbula e da metáfise proximal do fêmur de ratos Wistar. Para relacionar as descobertas à fisiopatologia da OMAB, o regime de administração de BF de um modelo animal relevante desta lesão foi reproduzido. Seis animais receberam AZ (0,6 mg / kg) e seis receberam solução salina no mesmo volume (Controles). Os compostos foram administrados por via intraperitoneal em cinco doses a cada 28 dias. A eutanásia dos animais ocorreu após 150 dias de início da terapia. As hemimandíbulas e fêmures direitos foram escaneados usando Micro-tomografia computadorizada (Micro-CT) de alta resolução (14 m). Para a primeira análise realizada neste estudo, os dados morfométricos do osso esponjoso foram calculados na região do segundo e primeiro molar na mandíbula e na metáfise do fêmur usando CTAnalyzer (Bruker, Bélgica). Para a segunda análise, cinco amostras de hemimandíbulas de cada grupo foram cortadas em lâminas histológicas (5 m) e coradas com Hematoxilina e Eosina. Para comparar os parâmetros morfométricos na Micro-CT e histologia, as imagens de Micro-CT foram espacialmente alinhadas à histologia. Os dados morfométricos do osso alveolar foram calculados usando o software CTAnalyzer (Bruker, Bélgica) na região entre as raízes mesial e distal do primeiro molar. A densidade da área vascular (área vascular/área total; VA/TA) e os dados histomorfométricos ósseos foram estimados usando Axiovision na mesma região (entre as raízes mesial e distal do primeiro molar). Foi adotada significância estatística de 5% ( = 0,05). Os animais tratados com AZ apresentaram aumento significativo na porcentagem de volume ósseo (p <0,05) com trabéculas mais espessas, osso mais compacto com menor separação trabecular na mandíbula e no fêmur. Na mandíbula, o aumento da densidade óssea e diminuição da separação trabecular foram fortemente correlacionados com a diminuição da área vascular observada no grupo AZ (p <0,05). Em conclusão, o tratamento de longa duração com altas doses de AZ foi significativamente associado ao aumento na densidade óssea e à diminuição dos espaços medulares, canais nutritivos e vasculatura do osso alveolar. A análise com Micro-CT revelou alterações semelhantes na estrutura óssea tanto na mandíbula quanto no fêmur do grupo AZ. / Bisphosphonates (BFs) are widely used in the treatment of osteolytic diseases such as bone metastases and osteoporosis. The osteonecrosis of the jaws related to BF (ONB) is characterized by the presence of exposed bone or bone that can be probed through a fistula that persists for more than eight weeks in patients with a history of BF therapy and without history of head and neck radiotherapy and / or without metastatic disease in the jaws. The incidence of ONB increases with potency, duration of treatment and dose of BF received. Thus far, the pathophysiology of ONB is unclear, hampering prevention and treatment. The aim of this study was to objectively assess the effect of long-term high-dose Zoledronic Acid (ZA) on cancellous bone in the jaw and femur of Wistar rats. In order to link our findings to the physiopathology of ONB, the therapeutic regiment of a relevant ONB animal model was reproduced. Twelve Wistar rats were randomly divided in two groups: six received Zoledronic acid (ZA; 0.6 mg / kg) and six (Controls) received saline solution in the same volume. The compounds were administrated intraperitoneally in five doses each 28 days. The rats were killed after 150 days of the therapy onset. Mandibles and femurs were scanned using a high-resolution (14m) micro-computerized tomography (Micro-CT). For the first analysis carried in this study, cancellous bone morphometric data were calculates in the region of the second and first molar in the mandible and in the proximal femur using CTAnalyzer (Bruker, Belgium). For the second analysis five samples were cut into histological slices (5m) and stained with Hematoxylin and Eosin. In order to compare the same morphological structures in Micro-CT and histology, the Micro-CT images were aligned to histology. Alveolar bone morphometric data (Micro-CT) was calculated using CTAnalyzer (Bruker, Belgium) in the region between the mesial and distal roots of the first molar. Blood vessels density and bone histomorphometric data were calculated using Axiovision (Carl Zeiss, Germany) in the same region used for Micro-CT evaluation. Statistical significance of 5% (=0.05) was adopted. ZA treated rats presented significant increase in the percentage of bone volume (p<0.05) with thicker trabeculae and more compact bone with smaller marrow spaces in the mandible and femur. In the mandible, the increase in bone density and decrease of marrow spaces size was strongly correlated with the decrease in the vascular area noticed in the ZA group (p<0.05). In conclusion, long-term high-dose ZA treatment was significant associated with the increase of bone density and the diminution of medullary spaces and nutritive canals size as well as decrease in vascularity of the alveolar bone. Micro-CT investigation showed similar changes in bone structure in the mandible and femur in the ZA group.

No description available.

Matematinis dantų lanko modeliavimas leidžia įvertinti funkcinę tam tikro paciento dantų lanko būklę ir analizuoti racionalius gydymo variantus. Dabar mechaninė žmogaus kramtomosios sistemos analizė sujungia daugiau anatominių detalių ir todėl žmogui gali atrodyti, jog pagrindinės mechaninės problemos yra išsprendžiamos. Deja, tai nėra tiesa. Viena iš pagrindinių problemų susieta su raumenų stiprinimu - ar turime mes aktyvinti savo kramtymo raumenis ir kodėl. Pradžioje ištyrėme probleminę sritį ir iki šiol gautus pasiekimus žmogaus kramtymo sistemos trimačiame modeliavime. Vėliau parinkome tinkamą programinę įrangą bei susipažinome su jos galimybėmis. Tada įvairių bandymų metu nustatėme kaip įvairios naudojamų programų funkcijos ir jų parametrai įtakoja duomenų apdorojimą ir remdamiesi šiais duomenimis sudarėme žmogaus kramtymo sistemos trimačio modeliavimo algoritmą. Pasinaudodami juo sukūrėme trimatį paciento kramtymo sistemos modelį. Šio darbo tikslas buvo pasirinkti įrankius bei sukurti naujus, kurie gali pagelbėti sudarant trimatį modelį iš tomografijos būdu gaut�� vaizdų. Turėjome atsižvelgti į taisykles ir apribojimus. Pagrindinis šio darbo rezultatas yra makro komanda sukurta „Image-Pro Plus“ programai, kuri yra naudojama koordinačių gavimui iš tomografijos būdu gautų vaizdų. Buvo daryti eksperimentai skirti apibrėžti faktoriams, įtakojantiems sukuriamo modelio kokybę. / Relationships between muscle tensions, jaw motions, bite and joint forces, and craniofacial morphology are not fully understood, and critical information is often difficult or impossible to obtain in experiments on living humans. The inaccessibility of the mandible and its related structures is a major obstacle to measure their internal forces and stresses, and understanding their effects. Computer modeling offers an alternative method for doing this. Despite its limitations, modeling appears to provide a useful conceptual framework for developing hypotheses regarding the role of stresses during human masticatory system function. Three-dimensional model of main elements of masticatory system was created from computed tomography images. Later this model will be improved with physical characteristics. The objective of this work is to select the set of tools and create the new ones which could be used to acquire the three dimensional model from tomography images. The rules and restrictions of using medical hardware should be taken into account. The main outcome of this work is a macro-command created for the “Image Pro Plus”, which is used to capture object coordinates from the tomography pictures. Experiments were made to define the factors which are influencing the quality of the created model.

Im Vortrag wird das Vorgehen zur Konstruktionsoptimierung mittels parametrischer FE-Simulation beschrieben. Die einzelnen Schritte werden dargestellt und am Beispiel eines Übertragungselements für Klauenkupplungen erläutert. Zunächst wird der Optimierungsgegenstand vorgestellt und die Festlegung der Entwurfsvariablen und Zielfunktionen beschrieben. Im Anschluss werden die Erstellung des FE-Modells und die Durchführung der Optimierungsrechnung schrittweise erläutert. Abschließend folgen ein Vergleich verschiedener Optimierungsmethoden und die Zusammenfassung. Als Software wurden ANSYS und Autodesk Inventor verwendet.

The focus of this thesis was to study an action that humans perform regularly, namely, to hold a morsel between the teeth and split it into smaller pieces. Three different issues related to this biting behavior were addressed:  (1) the effect of redu­c­ed perio­dontal tissues on food holding and splitting behavior; (2) the behavioral conse­quences of performing different bite tasks with different functional requirements, i.e., to split a peanut half resting on a piece of chocolate or to split both the peanut and the chocolate; and (3) the reflex modulations resul­ting from such a change in the intended bite action. The main conclusions from the experi­mental studies were the following: First, perio­dontitis, an inflam­matory disease that destroys the peri­o­dontal ligaments and the embedded perio­dontal mechanoreceptors, causes significant impairments in the masticatory abili­ty: the manipulative bite forces when holding a morsel are elevated compared to a matched control population and the bite force development prior to food split is altered. These changes are likely due to a combination of reduced sensory informa­tion from the damaged ligaments and to changes in the bite stra­tegy secon­d­ary to the unstable oral situation. Second, people exploit the anatomy of jaw-closing muscles to regulate the amount of bite force that dissipates following a sudden unloading of the jaw. Such control is necessary because without mechanisms that quickly halt jaw-closing movements after sudden unloading, the impact forces when the teeth collide could otherwise damage both the teeth and related soft tissues. Splitting a piece of chocolate, for instance, regularly requires &gt;100N of bite force and the jaws collide within 5 ms of a split. On the other hand, when biting through heterogeneous food, the bite force needs to be kept high until the whole morsel is split. The required regulation is achieved by differen­tial­ly engaging parts of the masseter muscles along the anteroposterior axis of the jaw to exploit differences between muscle portions in their bite force generating capa­ci­ty and muscle shortening velocity. Finally, the reflex evoked by suddenly unloading the jaw—apparent only after the initial bite force dissipation—is modulated according to the bite intention. That is, when the intention is to bite through food items with multiple layers, the reflex response in the jaw opening muscles following a split is small, thus minimizing the bite force reduction. In contrast, when the intention is to rapidly decrease the bite force once a split has occurred, the reflex response is high. This pattern of reflex modulation is functionally beneficial when biting through heterogeneous food in a smooth manner. The presented studies show the significance of integrating cogni­tive, physiological and anatomical aspects when attempting to understand human masticatory control.

Doctor of Philosophy(PhD) / Hyperparathyroidism, a disease of the parathyroid glands, is one of the most common endocrinopathies, having a prevalence of 1 – 3 per 1000 individuals. It is characterised by calcium insensitive hypersecretion of parathyroid hormone, and increased cell proliferation. While the treatment for familial as well as many sporadic tumours associated with hyperparathyroidism includes parathyroidectomy, the extent of surgery and the follow-up monitoring regime, are dependent on accurate clinical and histopathological classification of the lesion. However, overlaps in histopathological and morphological features confound distinctions between the three main classifications of adenoma, hyperplasia and carcinoma and differential diagnosis of these lesions remains challenging. At the start of this candidature in January 2002, the genes associated with two familial syndromes in which hyperparathyroidism may feature, Multiple Endocrine Neoplasia (MEN) 1 and 2 had been identified, respectively MEN1 and RET. In addition, overexpression or translocation of cyclin D1 had been identified in both benign and malignant sporadic lesions, indicating a role for cyclin D1 in parathyroid tumorigenesis. However, the underlying events leading either directly, or indirectly, to the development of a large proportion of parathyroid lesions are still largely unknown. The work described in this thesis has contributed to the understanding of parathyroid lesions and the diagnosis and prognosis of affected individuals. During this candidature, constitutive mutation of HRPT2 was associated with Hyperparathyroidism–Jaw Tumour syndrome (HPT-JT). HRPT2 mutation analysis and loss of heterozygosity studies at 1q24-32 in parathyroid tumours presented in this thesis identified the strong association of HRPT2 mutation with sporadic parathyroid malignancy. In addition, 2-hits affecting HRPT2 were identified in several tumours suggestive of a role for HRPT2 as a tumour suppressor gene in sporadic parathyroid tumorigenesis. Microarray analysis of parathyroid tumours presented in this thesis identified three broad clusters of tumours. Cluster 1 comprised predominantly hyperplastic specimens and also included the normal tissue. Cluster 2, the most robust of the clusters, consisted of tumours harbouring HRPT2 mutations. The HPT-JT-associated tumours, both benign and malignant, and sporadic carcinomas, comprised this cluster. Cluster 3 contained the majority of the sporadic adenoma specimens, some hyperplasia, as well as all of the MEN 1-associated tumours. The cluster data is strongly suggestive that parathyroid tumours with somatic HRPT2 mutation, or tumours developing on a background of germline HRPT2 mutation, follow pathways distinct from those involved in mutant MEN 1-related parathyroid tumours. The results of this work provide strong evidence for an adenoma to carcinoma progression model for parathyroid tumorigenesis in the presence of a germline HRPT2 mutation. With the knowledge that both HRPT2 and MEN1 have significant roles in familial as well as sporadic parathyroid tumorigenesis, assays for mutation screening of these two genes have been developed as part of this thesis. These assays will facilitate a rapid molecular diagnosis for patients with one of these familial syndromes. Furthermore, novel putative biomarkers for different parathyroid tumour subtypes have also been identified. VCAM1 and UCHL1 (PGP9.5) were found to be significantly overexpressed in tumours harbouring an HRPT2 mutation at both the transcript and protein level. These two molecules are suggested as putative biomarkers for the discrimination of sporadic carcinoma or HPT-JT-associated tumours. RALDH2 transcript and protein were highly significantly overexpressed in the hyperplasia class relative to the adenoma class, and this molecule is suggested as a putative biomarker for discrimination of these classes of parathyroid tumours. These biomarkers may assist in the accurate diagnosis and prognosis of hyperparathyroidism. Large cohort studies of these putative biomarkers will be required to determine their robustness in discriminating parathyroid tumour subtypes. Further studies of their putative role in parathyroid tumorigenesis may identify them as novel molecular targets for future therapeutics to treat both hyperplastic and neoplastic parathyroid lesions.

Doctor of Philosophy(PhD) / Hyperparathyroidism, a disease of the parathyroid glands, is one of the most common endocrinopathies, having a prevalence of 1 – 3 per 1000 individuals. It is characterised by calcium insensitive hypersecretion of parathyroid hormone, and increased cell proliferation. While the treatment for familial as well as many sporadic tumours associated with hyperparathyroidism includes parathyroidectomy, the extent of surgery and the follow-up monitoring regime, are dependent on accurate clinical and histopathological classification of the lesion. However, overlaps in histopathological and morphological features confound distinctions between the three main classifications of adenoma, hyperplasia and carcinoma and differential diagnosis of these lesions remains challenging. At the start of this candidature in January 2002, the genes associated with two familial syndromes in which hyperparathyroidism may feature, Multiple Endocrine Neoplasia (MEN) 1 and 2 had been identified, respectively MEN1 and RET. In addition, overexpression or translocation of cyclin D1 had been identified in both benign and malignant sporadic lesions, indicating a role for cyclin D1 in parathyroid tumorigenesis. However, the underlying events leading either directly, or indirectly, to the development of a large proportion of parathyroid lesions are still largely unknown. The work described in this thesis has contributed to the understanding of parathyroid lesions and the diagnosis and prognosis of affected individuals. During this candidature, constitutive mutation of HRPT2 was associated with Hyperparathyroidism–Jaw Tumour syndrome (HPT-JT). HRPT2 mutation analysis and loss of heterozygosity studies at 1q24-32 in parathyroid tumours presented in this thesis identified the strong association of HRPT2 mutation with sporadic parathyroid malignancy. In addition, 2-hits affecting HRPT2 were identified in several tumours suggestive of a role for HRPT2 as a tumour suppressor gene in sporadic parathyroid tumorigenesis. Microarray analysis of parathyroid tumours presented in this thesis identified three broad clusters of tumours. Cluster 1 comprised predominantly hyperplastic specimens and also included the normal tissue. Cluster 2, the most robust of the clusters, consisted of tumours harbouring HRPT2 mutations. The HPT-JT-associated tumours, both benign and malignant, and sporadic carcinomas, comprised this cluster. Cluster 3 contained the majority of the sporadic adenoma specimens, some hyperplasia, as well as all of the MEN 1-associated tumours. The cluster data is strongly suggestive that parathyroid tumours with somatic HRPT2 mutation, or tumours developing on a background of germline HRPT2 mutation, follow pathways distinct from those involved in mutant MEN 1-related parathyroid tumours. The results of this work provide strong evidence for an adenoma to carcinoma progression model for parathyroid tumorigenesis in the presence of a germline HRPT2 mutation. With the knowledge that both HRPT2 and MEN1 have significant roles in familial as well as sporadic parathyroid tumorigenesis, assays for mutation screening of these two genes have been developed as part of this thesis. These assays will facilitate a rapid molecular diagnosis for patients with one of these familial syndromes. Furthermore, novel putative biomarkers for different parathyroid tumour subtypes have also been identified. VCAM1 and UCHL1 (PGP9.5) were found to be significantly overexpressed in tumours harbouring an HRPT2 mutation at both the transcript and protein level. These two molecules are suggested as putative biomarkers for the discrimination of sporadic carcinoma or HPT-JT-associated tumours. RALDH2 transcript and protein were highly significantly overexpressed in the hyperplasia class relative to the adenoma class, and this molecule is suggested as a putative biomarker for discrimination of these classes of parathyroid tumours. These biomarkers may assist in the accurate diagnosis and prognosis of hyperparathyroidism. Large cohort studies of these putative biomarkers will be required to determine their robustness in discriminating parathyroid tumour subtypes. Further studies of their putative role in parathyroid tumorigenesis may identify them as novel molecular targets for future therapeutics to treat both hyperplastic and neoplastic parathyroid lesions.