Thesis (M.D.S.)--University of Hong Kong, 1993. / Photocopy of original typescript.

Thesis (M.D.S.)--University of Hong Kong, 1993. / Also available in print.

Trabajo de Investigación Requisito para optar al Título de Cirujano Dentista / ntroducción: Se ha documentado ampliamente en la bibliografía internacional sobre las manifestaciones orales y máxilofaciales asociadas a la infección por VIH/SIDA y cuál es su frecuencia de aparición en este tipo de pacientes. Sin embargo, en nuestro país, los datos epidemiológicos de este tipo de manifestaciones son escasos y desactualizados. Contar con esta información es esencial para optimizar los recursos involucrados en el tratamiento integral de estos pacientes. Objetivo: Determinar frecuencia de manifestaciones orales, asociadas y no asociadas a infección por VIH, en pacientes adultos VIH/SIDA del Hospital San Juan de Dios y describirlas según género y edad. Materiales y métodos: Estudio observacional descriptivo de corte transversal en adultos diagnosticados con VIH/SIDA en atención en el Hospital San Juan de Dios, en un periodo de 18 meses. Se realizó examen intraoral y el diagnóstico de las lesiones fue basado en el criterio clínico de la European Comunity Clearing Clearinghouse (ECC), y en estudios histopatológicos e imagenológicos complementarios al diagnóstico. Todos los pacientes incluidos en el estudio aceptaron participar voluntariamente y firmaron el consentimiento informado. Resultados: 68 pacientes, 52 hombres (76,5%) y 17 mujeres (23,5) cumplieron los criterios de inclusión. 23 pacientes presentaron al menos una lesión oral relacionada a la infección por VIH (33,8%), en donde las lesiones más prevalentes fueron las Úlceras mayores y el Papiloma oral (8,8%), seguida de la Candidiasis oral (5,9%), la Queilitis Angular (5,9), Sarcoma de Kaposi (4,4%), Linfoma no Hodgkin (2,94%), Gingivitis Ulceronecrotizante y Leucoplasia Pilosa (1,47%). Mientras que las lesiones no asociadas a VIH como Caries y Enfermedad Periodontal se presentaron en 31 pacientes (45,5%). 4 Conclusión: Un 33,8% de los pacientes estudiados presentaron al menos una lesión asociada a VIH/SIDA, en donde la lesión oral asociada a la infección por VIH más frecuente corresponde a Papiloma oral y Úlceras orales mayores. Las lesiones orales no asociadas a VIH/SIDA más frecuentes fueron la Caries y la Enfermedad Periodontal.

Trabajo de investigación requisito para optar al título de Cirujano-Dentista / Introducción: Lesiones bucomaxilofaciales conocidas se asocian con estados de inmunosupresión en pacientes VIH/SIDA. La presencia de estas lesiones puede ser el primer signo clínico de la infección y ser una importante herramienta para monitorizar la progresión y pronóstico de ésta. Objetivo: Determinar la asociación entre las lesiones bucomaxilofaciales y diferentes niveles de inmunosupresión determinados por el recuento de linfocitos TCD4+ en: Ausente (≥ 500 células/ml), Moderada (entre 201 células/ml y 499 células/ml) y Severa (≤200 células/ml) en pacientes adultos VIH/SIDA en atención en el Hospital San Juan de Dios. Materiales y Método: Estudio observacional analítico de corte transversal en adultos diagnosticados con VIH/SIDA en atención en el Hospital San Juan de Dios, durante un periodo de 17 meses. Se realizó examen intraoral y el diagnóstico de las lesiones bucomáxilofaciales fue de acuerdo al criterio clínico de EEC clearing house y a estudios imagenológicos e histopatológicos. El grado de inmunosupresión se basó en el recuento de linfocitos TCD4+ más cercano al momento del examen odontológico. Pacientes con diabetes, alcoholismo u otra condición que provoque inmunosupresión fueron excluidos, al igual que las pacientes embarazadas que pueden presentar manifestaciones orales propias de su condición. Todos los pacientes incluidos en el estudio aceptaron participar voluntariamente y firmaron el consentimiento informado. Los datos fueron analizados mediante el test paramétrico T-Student para variables continuas y en el caso de variables dicotómicas o categóricas se utilizó el test de chi cuadrado de Pearson y Odds Ratio. Se utilizó un nivel de confianza de 95% cuando correspondió. Resultados: 60 pacientes cumplieron con los criterios de inclusión. Dentro del grupo, 11 pacientes correspondieron a individuos del sexo femenino (18,3%) y 49 del sexo masculino (81,6%). La edad promedio fue de 40 ±1,44 años. 2 El 35% de los pacientes presentaba lesiones orales asociadas a infección por VIH con un recuento promedio de linfocitos TCD4+ de 299 células/ml y el 65% restante presentaba un recuento promedio de 348 células/ml, sin existir diferencia estadísticamente significativa (p=0,38). Por otro lado, se observó que es 3,275 veces más probable presentar una lesión asociada a VIH/SIDA cuando el paciente se encuentra en inmunosupresión determinado por recuentos de linfocitos TCD4+ menores a 500 células/ml. (OR=3,275). Las lesiones orales asociadas a VIH/SIDA más comúnmente observadas fueron las úlceras orales (10%) y el papiloma (0,8%). El Sarcoma de Kaposi se relacionó con recuentos de linfocitos TCD4+ bajos (p=0,061). Conclusión: Los pacientes con lesiones orales asociadas a infección por VIH presentaron un recuento de linfocitos TCD4+ promedio menor (299 cél/ml) que los que no presentaban lesiones asociadas (348 cél/ml) y existe mayor probabilidad de presentar lesiones asociadas a VIH/SIDA cuando existe inmunosupresión determinado por recuentos de linfocitos TCD4+ <500 cél/ml. (OR=3,275). Los pacientes que presentaron sarcoma de Kaposi se relacionaron con recuentos de linfocitos TCD4+ muy bajos (<50 cél/ml), lo que podría relacionarse con inmunosupresión severa.

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 121-133).

It is a striking observation that tissue of patients invaded by the deep mycoses often lacks evidence of an inflammatory response. This lack of host response is often attributed to neutropenia secondary to chemotherapy. However, systematic studies do not support this simplistic explanation. However, invasive fungal lesions are characterized by abundant fungal functional amyloid, which in turn is bound by serum amyloid P component (SAP). We postulate that SAP is important in the local immune response in invasive fungal infections. The interaction between fungal functional amyloid, SAP, and the immune response in deep mycoses is discussed.

Nas últimas décadas, houve aumento progressivo das infecções hospitalares por leveduras principalmente, do gênero Candida. A fonte de infecção pode ser endógena ou exógena, desde que esporos unicelulares de leveduras, permanecem viáveis por meses sobre superfícies bióticas ou abióticas. Diversas espécies de leveduras são encontradas em pele e mucosas de indivíduos sadios. Em estado saprofítico ainda, as leveduras encontram-se no trato gastrintestinal humano mas, a relação entre a presença desses microorganismos e sua patogenicidade está associada a diversos fatores predisponentes, tais como: número e variedade de sítios topográficos colonizados, uso prolongado de antibióticos, infecções associadas causadas por outros microorganismos e particularmente, distúrbios imunológicos ou metabólicos. Leveduras do trato gastrintestinal podem ser transmitidas, via fecal-oral diretamente ou de modo indireto, de indivíduo para indivíduo. A transmissão de uma cepa em estado saprofítico para um hospedeiro suscetível, pode resultar em colonização seguida de infecção. A gravidade do quadro clínico depende de condições do hospedeiro e características do agente etiológico que engloba fatores de virulência e resistência a antifúngicos. Esses atributos são importantes em Candida albicans na qual, enzimas com atividade de fosfolipase e proteinase são marcadores de virulência. De outro modo, fenótipos de resistência, ocorrem, com maior freqüência, em espécies não-Candida albicans. Dada a possibilidade de instalação de doença endógena e a dispersão de cepas virulentas e resistentes, a partir de colonização gastrintestinal, estudos que contribuam para a determinação desses agentes constituintes da microbiota de pacientes internados, são importantes para o conhecimento da história natural das infecções nosocomiais por leveduras. Os objetivos deste trabalho foram avaliar o trato intestinal como fonte potencial de infecção hospitalar por leveduras, descrevendo as espécies prevalentes nas primeiras horas de internação e possíveis alterações temporais, quanto a fenótipo de virulência e resistência a antifúngicos. Foram analisadas 281 amostras de leveduras isoladas de 66 crianças internadas em unidades de pediatria e semi-intensiva de hospitais públicos das cidades de São Paulo e Guarulhos, Brasil. As amostras foram isoladas de fezes coletadas nas primeiras horas de internação e durante o período de internação. A identificação das leveduras quanto a gênero e espécie foram realizadas por métodos tradicionais, analisando aspectos morfológicos e fisiológicos. A capacidade de produção de enzimas, fosfolipase e proteinase, foram verificadas conforme proposto por Price et al. 1982 e Ruchël et al., 1982. A sensibilidade aos antifúngicos: anfotericina B (AMB), fluconazol (FZ), itraconazol (IZ), cetoconazol (CZ) e nistatina (NIS) foram analisada pela técnica de difusão por discos (CECON São Paulo, Brasil). Amostras resistentes ou com sensibilidade intermediária, foram re-avaliadas pelo método de microdiluição segundo NCCL (1997) modificado por EUCAST (2002). As espécies isoladas foram: Candida tropicalis (32,7%), C.albicans (29,9%), C.parapsilosis (27, 1%), Trichosporon cutaneum e T.inkin (3,2%), Rhodotorula mucilaginosa e R.glutinis (0,7%), C.krusei (3,6%), C.guilliermondii (2,1%), C.glabrata (0,4%) e C.kefyr (0,4%). A atividade enzimática foi observada na maioria das 84 amostras de C. albicans, sendo 96% de fosfolipase e 95% de proteinase. Entre as espécies não-albicans do gênero Candida foi verificada atividade em 97% de fosfolipase e 67% de proteinase. Amostras menos sensíveis às drogas azólicas, ou seja, amostras resistentes ou com sensibilidade dependente da dose, foram encontradas em 4,3% das 281 amostras de leveduras, sendo maior porcentagem observada em C.krusei (90%). Conclui-se que existem leveduras de diversas espécies em fezes de população pediátrica hospitalizada, com fenótipos de virulência e resistência a antifúngicos. A manutenção desses fenótipos durante o período de internação pode representar fator de risco para infecção hospitalar endógena, ou ainda, fonte de dispersão de patógenos em potencial, no meio ambiente hospitalar. / At the last decades the nosocomial infections caused by yeasts raised significantly especially by Candida yeasts. The infections source can be endogen or exogenous, since spores of unicellular and multicellular are kept viable for months and several yeasts species are found in skin and mucosa of healthy people. In a saprophytic state yeasts are found in the human gastrointestinal tract but the relationship between the presence of these microorganisms and their pathology is associated with several facts such as: number, variety of sites colonized, effective use of antibiotics, associated infections caused by another microorganisms and mainly disturbance in due to lack of immunity and metabolic. Yeasts in the gastrointestinal tract can be transmitted fecal-oral direct or indirectly from an individual to another. The transmission of a strain in a saprophytic state to a host can result in colony followed by infection. The infection can be serious depending on the host conditions and the etiologic agent that includes virulent factor and resistance to antifungal drugs. These attributes are important to Candida albicans in which enzymes with phospholipase activity are responsible for virulent factors. Resistance phenotypes, otherwise it should occur more frequently in non-albicans species. Concerning the possibility of an endogen disease and the spread of virulent and resistant strains, from the gastrointestinal colony, studies that contribute to determine these agents that constitute the microbiota of patients, are important to know the natural story of nosocomial infections caused by yeasts. This work aims at evaluating the intestinal tract as a source of hospital infections by yeasts describing the remaining species in the first hours and a possible change depending on the time that may happen to virulent phenotypic and resistance to ant fungi. Two hundred eighty one yeast samples from sixty-six children attended in pediatric and semi-intensive units in 2 public hospitals located in São Paulo and Guarulhos cities in Brazil were analyzed. The fecal samples were collected at the first hours after and during their arrival at the hospital. To identify the yeasts according to their gender and species traditional methods were used, analyzing morphological and physiological aspects. The ability to produce enzymes phospholipase and proteinase was verified the same way it was proposed by Price et al. 1982 and Ruchel et al. 1982. The sensibility to antifungals: amphotericin B (AMB), f1uconazole (FZ), ketoconazole (CZ) e nistatin (NIS), was analyzed by the diffusion technical by disks (CECON São Paulo, Brazil). Resistant samples or with intermediate sensibility were confirmed by micro-dilution method according to NCCLS (1997) modified by EUCAST (2002). The isolated species were: Candida tropicalis (30%), C.parapsilosis (27%), C.krusei (4%), Trichosporon cutaneum e T.inkin (3%), Rhodotorula mucilaginosa e R.glutinis (2%), C.guilliermondii (2%), C.glabrata (1%) and C.kefyr (1%). Enzymatic activity was verified in most of the 84 C.albicans samples being 96% of phosfolipase and 95% of proteinase production. Among the non-albicans species of Candida it was observed 97% of phospholipase and 67% of proteinase activity. Less sensitive samples to azoic drugs including resistant or SDD sensibility, which depends on the achieved dose, were found in 4.3% of the 281 samples of yeast. The hugest percentage was observed in C.krusei (90%). We can conclude that different yeast species occur in stools of pediatric population hospitalized, including virulent strains and antifungal resistant phenotypes. The persistent of these phenotypes in the intestinal tract during hospitalization period may represents a risk facto r contributing to endogen infection, or play a role in dissemination of potential pathogens inside a nosocomial environment.

"Vulvovaginal candidiasis (VVC) is a mucosal infection caused by Candida species and represents one of the most common clinical problems in women of reproductive age (68,71). Annually in the United States there are approximately 13 million cases of VVC, resulting in 10 million gynecologic office visits per year (38). It is estimated that 75% of women will experience at least one episode in their lifetime, with a projected 50% of all women experiencing multiple episodes (23). Candida albicans is a dimorphic commensal organism of the urogenital and gastrointestinal tracts and has been identified as the main pathogenic agent in VVC, accounting for approximately 85-90% of patients with positive cultures (52). Despite extensive research, the invasive mechanism of vaginal yeast infections is not well understood. Traditionally it has been assumed that changes in the host vaginal environment promote the dimorphic transition from blastospore to hyphae, resulting in a shift from asymptomatic colonization to symptomatic vaginitis (28). In contrast to the normal, systemic immune response, which confers an aseptic environment for tissue and organs, immune responses at the mucosal level are designed to prevent tissue invasion and local disease while maintaining an indigenous flora that could be both beneficial and pathogenic (28). Since fungi are eukaryotic, the vital cellular mechanisms that are usually targeted by modern pharmacologic agents, such as DNA replication and protein translation, are either conserved or have a strong homology to their human orthologs. Obtaining a better understanding of natural fungal suppression mechanisms and molecules at the mucosal level may pave the way for the development of more efficacious drugs or preventative regiments. The mechanism by which the human immune system is able to resist fungal invasion at the vaginal mucosa is unknown. Our research was aimed at finding any host factors that might play a role in the suppression of or prevention of a fungal infection at the vaginal mucosa. In order to screen candidate molecules that might be important in this type of vaginal defense, we chose a pathogenic C. albicans strain, SC5314, to test fungal cell viability upon introduction of the candidate molecules. We have identified a host factor that exhibits strong fungicidal activity when organically extracted from both human and bovine serum albumins. Characterization of this factor through organic extractions and acetone separations reveal that this molecule is a non-polar lipid. Serum samples that have been thoroughly stripped of fatty acids and other lipophilic molecules show no apparent fungicidal activity in cell viability assays. Since the factor is extractable from both human and bovine serum albumins, it may be conserved among mammals. Identification and characterization of this molecule may play a pivotal role in understanding host-Candida interactions at the mucosal membrane interface. Due to its human origin, the use of this factor as an antifungal would be extremely advantageous in regards to FDA (Food and Drug Administration) guidelines and ADMET (Adsorption, Distribution, Metabolism, Excretion, Toxicology) properties. "

Thesis (Ph. D.)--University of Wisconsin--Madison, 2006. / Includes bibliographical references. Also available on the Internet.

Thesis (Ph.D.) -- University of Adelaide, Dept. of Dentistry, 2002. / "8th July 2002." Includes bibliographical references (leaves 276-308).