Title page, table of contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / A major clinical dilemma in the management of patients with early stage breast cancer is determining which patients are at risk of subsequent recurrence so that these patients may be offered adjuvant therapies. Currently, the major prognostic factors used in determining prognosis including nodal status and tumour size fail to identify up to 30% of patients classified as having low risk disease who subsequently recur with breast cancer. Therefore, there is a great need for new methodologies that can sensitively and specifically identify disseminated disease. During this study, the major aims were to use immunobead-based and methylation-based methods for the detection of occult disseminated disease in peripheral blood samples obtained from breast cancer patients. Firstly, an RT-PCR assay was developed that identified a panel of gene specific markers that could be used for sensitive and specific detection of any circulating epithelial cells with minimal risk of false positive results from contaminating haematopoietic compartment cells. These gene markers were used to assess breast cancer patients using immunobead enrichment prior to RT-PCR (IB RT-PCR) and resulted in the detection of circulating epithelial cells in 21157 peripheral blood samples. Importantly, some of these patients had been deemed lymph node negative and at low risk of relapse. Furthermore, it was decided to screen for gene promoter region methylation in freely circulating DNA in the plasma fraction, and in DNA from the nuclei of epithelial cells captured using the immunomagnetic enrichment method. The analysis of gene loci methylation of patient samples was conducted concurrently with the analysis of the frequency of gene loci methylation in mononuclear cells from normal individuals. Surprisingly, a high proportion of normal individuals were methylated at high frequency at gene loci that have previously been reported to be tumour specific. This finding had implications for the concurrent study using methylation as a marker of occult disseminated disease in breast cancer patients. The analysis of blood samples using the methodology presented in this thesis for the early detection of breast cancer dissemination, has the potential to be developed to a point where it can be introduced into the clinical setting. Once fully developed and validated, this minimally invasive methodology, that causes little discomfort to the patient, could help to improve breast cancer staging, and provide important prognostic information ensuring the identification of those early stage breast cancer patients with the greatest risk of relapse and in most need of adjuvant therapies. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1097066 / Thesis (Ph.D.) -- University of Adelaide, Dept. of Medicine, 2003

Title page, table of contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / A major clinical dilemma in the management of patients with early stage breast cancer is determining which patients are at risk of subsequent recurrence so that these patients may be offered adjuvant therapies. Currently, the major prognostic factors used in determining prognosis including nodal status and tumour size fail to identify up to 30% of patients classified as having low risk disease who subsequently recur with breast cancer. Therefore, there is a great need for new methodologies that can sensitively and specifically identify disseminated disease. During this study, the major aims were to use immunobead-based and methylation-based methods for the detection of occult disseminated disease in peripheral blood samples obtained from breast cancer patients. Firstly, an RT-PCR assay was developed that identified a panel of gene specific markers that could be used for sensitive and specific detection of any circulating epithelial cells with minimal risk of false positive results from contaminating haematopoietic compartment cells. These gene markers were used to assess breast cancer patients using immunobead enrichment prior to RT-PCR (IB RT-PCR) and resulted in the detection of circulating epithelial cells in 21157 peripheral blood samples. Importantly, some of these patients had been deemed lymph node negative and at low risk of relapse. Furthermore, it was decided to screen for gene promoter region methylation in freely circulating DNA in the plasma fraction, and in DNA from the nuclei of epithelial cells captured using the immunomagnetic enrichment method. The analysis of gene loci methylation of patient samples was conducted concurrently with the analysis of the frequency of gene loci methylation in mononuclear cells from normal individuals. Surprisingly, a high proportion of normal individuals were methylated at high frequency at gene loci that have previously been reported to be tumour specific. This finding had implications for the concurrent study using methylation as a marker of occult disseminated disease in breast cancer patients. The analysis of blood samples using the methodology presented in this thesis for the early detection of breast cancer dissemination, has the potential to be developed to a point where it can be introduced into the clinical setting. Once fully developed and validated, this minimally invasive methodology, that causes little discomfort to the patient, could help to improve breast cancer staging, and provide important prognostic information ensuring the identification of those early stage breast cancer patients with the greatest risk of relapse and in most need of adjuvant therapies. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1097066 / Thesis (Ph.D.) -- University of Adelaide, Dept. of Medicine, 2003

abstract: The Santa Gertrudis Mining District of Sonora, Mexico contains more than a dozen purported Carlin-like, sedimentary-hosted, disseminated-gold deposits. A series of near-surface, mostly oxidized gold deposits were open-pit mined from the calcareous and clastic units of the Cretaceous Bisbee Group. Gold occurs as finely disseminated, sub-micron coatings on sulfides, associated with argillization and silicification of calcareous, carbonaceous, and siliciclastic sedimentary rocks in structural settings. Gold occurs with elevated levels of As, Hg, Sb, Pb, and Zn. Downhole drill data within distal disseminated gold zones reveal a 5:1 ratio of Ag:Au and strong correlations of Au to Pb and Zn. This study explores the timing and structural control of mineralization utilizing field mapping, geochemical studies, drilling, core logging, and structural analysis. Most field evidence indicates that mineralization is related to a single pulse of moderately differentiated, Eocene intrusives described as Mo-Cu-Au skarn with structurally controlled distal disseminated As-Ag-Au. / Dissertation/Thesis / M.S. Geological Sciences 2011

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2013-10-16T19:18:46Z No. of bitstreams: 1 Dayana Santos Mendes. Imunopatogenese da ...2011.pdf: 1813082 bytes, checksum: d271ed0b72f8be8c290f132d78e6e132 (MD5) / Made available in DSpace on 2013-10-16T19:18:46Z (GMT). No. of bitstreams: 1 Dayana Santos Mendes. Imunopatogenese da ...2011.pdf: 1813082 bytes, checksum: d271ed0b72f8be8c290f132d78e6e132 (MD5) Previous issue date: 2011 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Leishmania (Viannia) braziliensis causa várias formas de doença clinica cutânea, entre elas a forma cutânea disseminada (LD) com uma úlcera cutânea e lesões secundárias disseminadas por mais de duas regiões do corpo. Esta forma além da úlcera inicial apresenta manifestação clínica de múltiplas pápulas e lesões não ulceradas. Neste estudo, descrevemos a histopatologia das lesões não ulceradas da LD, correlacionando-a com a extensão da área inflamada com células CD4, CD20, CD68, CD31 e células de fator de von Willebrand (vW). Metodologia: Dezoito biópsias de lesões de pacientes diagnosticados com LD por critérios clínicos, teste cutâneo de Montenegro positivo e cultivo positivo para L. braziliensis dos aspirados locais das lesões. A análise histopatológica foi feita a partir dos fragmentos de tecidos corados com Hematoxilina e Eosina (HE). A quantificação da área inflamada e células positivas para CD4, CD20, CD68, CD31 e vW foi avaliada com o auxílio do programa Image-Pro Plus (Media Cibernetics). Resultados: Infiltrado inflamatório linfoplasmocitário perivascular e formação de granulomas são achados comuns nas lesões papulares causadas por L. braziliensis. A extensão da área de inflamação variou de 3% a 73%. Houve uma correlação linear significativa entre a extensão da inflamação e a presença de vasos vW+. As células mais frequentes no infiltrado inflamatório foram os macrófagos CD68+, seguido por células B CD20+ e células T CD4+. Houve uma correlação linear significante entre células CD4+ e CD20+ e a área inflamada. Amastigotas foram detectadas por HE e imunohistoquímica em nove biópsias, todos os dezoito aspirados foram positivos para L. (Viannia) braziliensis nos cultivos in vitro. Conclusão: Pela análise histopatológica e imunohistoquímica em lesões fechadas causadas por L. braziliensis, observamos a presença de inflamação crônica variável qualitativa e quantitativamente. Com a expansão da área de inflamação, células CD4+ aumentam proporcionalmente ao número de vasos encontrados e células CD20+. / Introduction: Skin infection by Leishmania (Viannia) braziliensis results in cutaneous and mucosal leishmaniasis. In between this clinical spectrum, disseminated leishmaniasis (DL) primary ulcer and/or ulcerated secondary lesions differs from other presentations by the clinical manifestation of multiple papules and non-ulcerated lesions. In this study, we describe the histopathology of DL non-ulcerated lesions correlating them with the amount of CD4, CD20, CD68, CD31 cells, and von Willebrand factor (vW) and with the amount of inflamed area which characterize immune inflammatory aspects. Methods: Eighteen biopsies from patients diagnosed by clinical criteria, positive skin tests, and fine needle aspirations in vitro cultivation were analyzed. Histopathological properties were determined by analyzing hematoxylin and eosin (HE) stained slides. To quantify the inflamed area and the number of cell positive for CD4, CD20, CD 68, CD31 and vW cell markers, Image-Pro (Media Cybernetics) software was used. Results: Diffuse lymphoplasmacytic perivascular infiltrates and granulomas were found in the dermal skin layer. Inflammation extent varied from 3% to 73% indicating a significant linear correlation with vW+ vessels and with graded patterns. The most frequent inflammatory cells were macrophages CD68+, followed by B cells CD20+, and T cells CD4+. A significant linear correlation between CD4+ and CD20+ cells with the total area of inflammation was also found. Amastigotes were visualized in immunostained or HE stained slides. All 18 biopsies were positive for L. (Viannia) braziliensis. Conclusion: Our findings suggest that chronic inflammation was present in all papules and was predominantly formed by macrophages, plasmacytes, T cells and B cells. As the area of inflammation expands, the vascular framework increases proportionally as the presence of CD20+ and CD4+ cells

A histoplasmose à considerada a micose endÃmica mais comum em seres humanos, com distribuiÃÃo cosmopolita e significativa incidÃncia no Brasil. Nas Ãltimas dÃcadas, Histoplasma capsulatum tem surgido como patÃgeno oportunista em indivÃduos com distÃrbios da imunidade celular, como aqueles em corticoterapia prolongada, transplantados, imunodeprimidos e principalmente que desenvolveram a sÃndrome da imunideficiÃncia adquirida (aids). A literatura dispÃe de poucos inquÃritos sorolÃgicos sobre a prevalÃncia dessa doenÃa no Brasil, dificultando o conhecimento sobre sua distribuiÃÃo. Nesse contexto, o Estado do Cearà tem-se destacado como Ãrea de elevada notificaÃÃo de casos de Histoplasmose Disseminada (HD) associada a aids no paÃs. A utilizaÃÃo de Sistemas de InformaÃÃes GeogrÃficas (SIG) na SaÃde PÃblica tem auxiliado na compreensÃo do processo saÃde-doenÃa em diversas situaÃÃes, como o planejamento e avaliaÃÃo de aÃÃes de saÃde, definiÃÃo de Ãreas de risco para incidÃncia de doenÃas ou anÃlise de dispersÃo espacial de epidemias. O presente estudo propÃe avaliar a distribuiÃÃo espacial dos casos de HD associada a aids no municÃpio de Fortaleza, CearÃ, ocorridos de 1999 a 2007.Dados sÃciodemogrÃficos e clÃnicos foram coletados em questionÃrio semiestruturado a partir de informaÃÃs contidas no registro do ServiÃo de Arquivo MÃdico e EstatÃstica do Hospital SÃo Josà de DoenÃas Infecciosas (SAME/HSJ), efetuando-se em seguida o georreferenciamento e anÃlise estatÃstica espacial dos casos com auxÃlio do software Terraview 4.0.0, utilizando-se os bairros e regionais (divisÃo polÃtico-administrativa da cidade) como unidades de agregaÃÃo. Foram identificados 238 casos de HD/aids, sendo excluÃdos 86 indivÃduos procedentes de outros municÃpios que nÃo Fortaleza. A razÃo entre os sexos masculino e feminino foi de 1,43, a mÃdia de idade foi de 40,3  12,8 anos, o nÃvel de escolaridade mais freqÃente ficou na faixa entre 4 e 7 anos de estudo (34,9%) e a maioria (53,02%) recebia no mÃximo trÃs salÃrios mÃnimos. Houve predomÃnio de desempregados (13,16%, p= 0.003), com a maioria (38,71%) correspondendo a mulheres. Setenta e cinco (64,7%) dos 116 bairros que compreendem o municÃpio de Fortaleza foram citados pelos pacientes como logradouro atual. A relaÃÃo da nuvem de pontos com mapas de indicadores sÃcioambientais demonstrou associaÃÃo com mÃdia e baixa cobertura de esgotamento sanitÃrio e mÃdio e baixo Ãndice de desenvolvimento humano. O Ãndice de domicÃlios particulares permanentes demonstrou que os casos se agruparam em Ãreas com alta densidade de casas. O presente trabalho à o primeiro estudo associando HD/aids e SIG no municÃpio de Fortaleza, permitindo localizar geograficamente o perfil de morbimortalidade por HD/aids na cidade, indicando Ãreas onde investigaÃÃes e intervenÃÃes sobre essas doenÃas devam acontecer. / Histoplasmosis is considered the most common endemic mycosis in humans, with acosmopolitan distribution and significant impact in Brazil. In recent decades, Histoplasma capsulatum has emerged as an opportunistic pathogen in individuals with impaired cellular immunity such as patients on prolonged corticosteroid therapy, transplant recipients, and immune compromised patients who developed acquire dimunideficiÃncia syndrome (AIDS). The published literature has few serological surveys on the prevalence of this disease in Brazil and little is known about its distribution; in this context, the State of Cearà has been identified as an area of high prevalence of cases of disseminated histoplasmosis (DH) associated with AIDS in this country. The use of Geographic Information Systems (GIS) in Public Health has aimed to understand the health-disease process in many situations, such as planning and evaluation of health actions, definition of risk areas for disease incidence or analysis of spatial dispersion epidemics. The goal of this study was to evaluate the spatial distribution of DH associated with AIDS cases from 1999 to 2007 in Fortaleza, CearÃ. The spatial analysis of DH / AIDS cases was based on medical records information obtained from the Medical and Statistics File System of the SÃo Josà Hospital of Infectious Diseases (SAME / HSJ) . Demographic and clinical data were collected in semi-structured questionnaires to characterize the population studied, and in sequence the geo referencing and spatial statistical analysis of cases was performed through the software Terra view 4.0.0, utilizing the districts as the aggregation units. We identified 238 cases of HD / AIDS; 86 individuals were from other municipalities and excluded. The males/females ratio was 1.43, the mean age was 40.3  12.8 years, the education level was more frequent in the range of 4 to 7 years of study (34.9% ) and most (53.02%) received up to 3 minimum wages. There was a predominance of unemployed (13.16%, p = 0.003) and the majority of them (38.71%) was women. Seventy-five (64.7%) of the 116 districts that comprise the city of Fortaleza were cited as home address by the patients. The analysis of Kernel maps with the social-environmental indicators showed an association with a medium and low sanitation coverage and medium and low Human Developing Index. The cases were clustered in areas with high density of houses. This is the first study associating DH / AIDS and GIS in Fortaleza, allowing the geographic localization of morbidity and mortality profile of DH / AIDS in this city, indicating areas where specific investigations and interventions should be carried out.

Central Nervous System (CNS) vasculitis is the most common life-threatening complication of coccidioidal meningitis. It is manifested by cerebral ischemia, hemorrhage, and infarction. We report a case of CNS vasculitis in a patient receiving chemotherapy and review of the literature on coccidioidal meningitis. The patient was treated with combination antifungal therapy and a short course of high dose corticosteroids with a modest improvement in her neurological examination after initiation of steroids.

No description available.

Das Krankheitsbild der disseminierten Schilddrüsen(SD)-Autonomie ist nur in Mitteleuropa bekannt und wird in der englischsprachigen Literatur nicht beschrieben. Die exakte Pathogenese der disseminierten SD-Autonomie, insbesondere ob es sich um ein eigenständiges Krankheitsbild oder nur um ein szintigrafisches Phänomen handelt, ist nicht geklärt. Daher war es Ziel dieser Arbeit, die klinische Entität der disseminierten Autonomie genauer zu klassifizieren, mit anderen SD-Autonomien zu vergleichen und weitere Erkenntnisse über die Pathogenese, insbesondere bezüglich des intrathyreoidalen Iodgehalts sowie TSH-Rezeptorkeimbahnmutationen dieser Erkrankung zu gewinnen.

Results of seismic surveys are routinely used to assess the presence of methane hydrate in deep ocean sediments. Accurate estimates of hydrate distribution and volume within the sediment are required to assess the potential of gas hydrate as an energy resource, driver for climate change or as a geotechnical hazard. However, seismic velocity may be affected not only by the quantity and morphology of the hydrate, but also by the properties of the host sediment, for example its particle size distribution and grain shape. This paper reports the results of experiments conducted to determine dynamic geophysical properties such as compressional wave velocity (Vp), shear wave velocity (Vs) and their respective attenuation measurements (Qp -1 and Qs -1) of specimens with varying amounts of disseminated methane hydrate within materials with different particle shapes and sizes. The results show that the impact of disseminated hydrate is affected both by mean particle size and by particle sphericity, with the surface area of the sediment grains influencing the spread of hydrate throughout a material and therefore it’s bonding capabilities. The sediments with 10% hydrate content show the highest surface areas correspond to the least increase in seismic velocity while sediments with low surface areas gives the most.

The South Manasan ultramafic intrusion (ca. 1880 Ma) located in the Early Proterozoic Thompson Nickel Belt (TNB) contains Ni and platinum group element (PGE) mineralization hosted by disseminated sulfide. Whole-rock Ni values range from 0.3 to 1.7 wt. % and total precious metals (TPMs) range from 0 to 1.3 ppm Pt + Pd + Au and equate to tenor values (i.e., metal in 100% sulfide) of 11-39 wt. % Ni and 8-27 ppm TPMs. The South Manasan intrusion is a steeply dipping sill-like body with a boudinaged outline having a strike length of approximately 1200 m, average width of 125 m and a minimum depth extent of 1000 m. The intrusion is composed of approximately 25% fresh dunite, 50% serpentine altered dunite and 25% tectonized and carbonate altered dunite. The most intense alteration is found near the intrusion’s margin where it is in contact with metasedimentary rocks of the Pipe Formation, part of the surrounding Ospwagan Group. In fresh dunite the sulfide assemblage characterized by an intercumulate texture is dominated by pentlandite with accessory pyrite; the latter having a symplectic-like texture. The pentlandite-pyrite assemblage in the serpentinized dunite, although still characterized overall by an intercumlate-texture, has well developed platy intergrowths with chlorite and serpentine. In the most intensely modified unit (the carbonate altered dunite) the sulfide assemblage consists primarily of pyrrhotite and pentlandite. Whole-rock geochemical data (n=360), modal mineralogy and mineral chemistry obtained on representative drill core throughout the South Manasan intrusion have been used to establish a type section in order to evaluate the relative roles of primary magmatic versus secondary (i.e., serpentinization, carbonate alteration and deformation) processes. These data indicate that the primary silicate-sulfide assemblage was systematically modified during : serpentinization, carbonate alteration and deformation of the South Manasan intrusion such that a sequence of primary versus secondary events can be established. Intrusion of the original komatiitic magma and formation of the South Manasan intrusion took place at a shallow level into consolidated Ospwagan Group sediments with subsequent contamination of this melt with crustal S. This triggered sulfide saturation and generation of an immiscible sulfide melt. Calculated Ni and TPM tenor values constrain the R factor to between 500 and 2500. The early crystallization of olivine inhibited the sulfide melt from settling to the bottom of the magma column and as a consequence, the sulfides now have a primary interstitial magmatic texture. The current sulfide association dominated by pentlandite>>pyrite>chalcopyrite has a mineral paragenesis that is consistent with subsolidus re-equilibration of a primary pentlanditepyrrhotite- chalcopyrite assemblage. The subsequent processes of serpentinization, deformation and carbonate alteration resulted in modifying the primary sulfide assemblages and their textures (i.e., to platy habits), but did not greatly alter the bulk composition, in particular metal contents, except for addition of volatiles (H2O, CO2). It is concluded therefore that the enrichment of the sulfide assemblage at South Manasan in Ni and PGEs is a consequence of a primary magmatic process involving high R factor and that the effects of later overprinting processes (alteration, deformation) are not responsible for the presently observed high-tenor sulfide association.