Regensburg, Univ., Diss., 2005.

München, Techn. Univ., Diss., 2004. / Enth. 2 Sonderabdr. aus: The Journal of Biological Chemistry ; 41. 2003 und: The Journal of Clinical Investigation ; 10. 2004

München, Techn. Univ., Diss., 2004.

Thesis (M.A.)--Northern Kentucky University, 2007. / Made available through ProQuest. Publication number: AAT 1441005. ProQuest document ID: 1283974301. Includes bibliographical references (p. 55-56)

Freie University, Diss., 2005--Berlin. / Dateiformat: zip, Dateien im PDF-Format. Erscheinungsjahr an der Haupttitelstelle: 2005.

Made available in DSpace on 2014-06-11T19:32:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2005-02-03Bitstream added on 2014-06-13T20:04:30Z : No. of bitstreams: 1 nascifjr_ia_dr_jab.pdf: 487838 bytes, checksum: 48d0ed37c6795976c360a3bc66e7fd1d (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Com o objetivo de avaliar a eficácia do ácido lático frente ao iodo na anti-sepsia após a ordenha na prevenção da mastite bovina, foram estudados 668 quartos mamários de vacas holandesas em dois rebanhos leiteiros, sendo um experimental e outro comercial. Para tanto adotou-se o delineamento experimental tipo split-herd baseado na redução da ocorrência natural de novos casos de infecções intramamárias (recomendado pelo protocolo do National Mastistis Council). Os resultados obtidos evidenciaram que o ácido lático apresentou uma eficácia de 57,4% na redução do número de novos casos de IIM causados por Corynebacterium spp., Staphylococcus spp. e Streptococcus spp. entre as vacas estudadas no rebanho experimental. No rebanho comercial a eficácia foi de 42,9% entre os casos de IIM determinados por Staphylococcus spp., porém não mostrou eficácia entre os casos de IIM determinados por Corynebacterium spp. e Streptococcus spp.. Tanto o ácido lático quanto o iodo não interferiram nas taxas de cura espontânea, persistência de IIM e na ocorrência de casos clínicos de mastite entre as vacas estudadas nos rebanhos experimental e comercial. A utilização do ácido lático na anti-sepsia dos tetos de vacas após a ordenha, mostrou-se eficaz na redução do número de novos casos de IIM, desde que acompanhada por outras medidas de controle. / With the objective of evaluate the efficacy of a lactic acid against an iodine postmilking teat dip in preventing bovine mastitis, 668 mammary quarters from Holsteins cows in two dairy herds, one experimental and other commercial, were studied. The National Mastitis Council recommended protocol for determining efficacy of a postmilking barrier teat dip based on reduction of naturally occurring new intramammary infections was used, in a split-herd experimental design. Results demonstrated that lactic acid showed an efficacy of 57.4% in reducing new intramammary infections caused by Corynebacterium spp., Staphylococcus spp. and Streptococcus spp., among the experimental herd cows. In the commercial herd, the efficacy was 42.9%, but only in reducing the number of new cases of intramammary infections caused by Staphylococcus spp., and not for new cases of intramammary infections caused by Corynebacterium spp., and Streptococcus spp. Both, lactic acid and iodine didn't interfere in spontaneous cure, intramammary infections persistence and clinical mastitis rates in experimental and commercial herds. The use of a lactic acid teat dip antisepsis after each milking was effective in reducing new cases of IMI, as part of a mastitis control program.

Sepse é um importante problema de saúde pública, uma vez que seu tratamento gera altos custos a um sistema de saúde já sobrecarregado. É uma síndrome de alta mortalidade e morbidade que afeta, em geral, pacientes jovens com plena capacidade produtiva. A identificação e o tratamento precoce desta síndrome reduzem a morbimortalidade, assim como o custo. A proteína C reativa (PCR) e a procalcitonina (PCT) são bem estudadas como ferramentas para diagnóstico de infecção bacteriana em imunocompetentes, mas seu uso como ferramenta diagnóstica ainda não está estabelecido em pacientes imunossuprimidos. Portanto, a proposta deste estudo é avaliar a acurácia diagnóstica destes biomarcadores, em pacientes críticos imunossuprimidos (vírus da imunodeficiência adquirida  HIV positivos, portadores de tuberculose (TBC), cirróticos e transplantados). Como o uso da proteína C ainda não está estabelecido, a primeira questão de pesquisa investigou seu potencial diagnóstico quando comparado ao teste padrão (cultural). O segundo artigo comparou a PCR com a PCT. Para isto foram realizados dois artigos de revisão sistemática com metanálise. O primeiro artigo comparou a acurácia em determinar infecção bacteriana em imunossuprimidos da PCR ao teste padrão-ouro (as culturas). A primeira revisão incluiu 1.418 pacientes e demonstrou uma boa acurácia da PCR como biomarcador no diagnóstico de infecção bacteriana, apresentando sensibilidade de 69% e especificidade de 76% com uma área sob a curva (AUC) de 0,77. Os resultados encontrados são similares aos da literatura para imunocompetentes,(3) sensibilidade de 75%, especificidade de 67% e Área Sob a Curva Receiver Operating Characteristic (AUROC) de 0,92. Quando a PCT foi comparada com a PCR, ambos os biomarcadores mostraram acurácia moderada na utilização como ferrramenta de diagnóstico de infecção bacteriana, com um diagnóstico da razão de chances (DOR) de 7,24 (95% CI (2,83-14,60) para PCT e de 5,56 (95% CI (5,21-10,30) para PCR. A PCT e a PCR apresentaram sensibilidade de 69% e 68% e uma especificidade de 75% e 71%, respectivamente. Ambas mostraram resultados semelhantes, podendo ser utilizadas no diagnóstico de sepse em imunossupressos. / Sepsis is a major public health problem, since its treatment generates high costs, a health system already overburdened. A high mortality and morbidity syndrome affects, in general, young patients with full production capacity. The identification and early treatment of this syndrome reduce morbidity and mortality as well as the cost. C-reactive protein (CRP) and procalcitonin (PCT) are well studied as tools for diagnosis of bacterial infection in immunocompetent patients, but its use as a diagnostic tool is not yet established in immunocompromised patients. Therefore, the purpose of this study is to evaluate the diagnostic accuracy of these biomarkers in immunosuppresses critical patients (human immunodeficiency virus, cirrhotic and transplant). As the use of the c protein is not yet established, the first research question investigated their diagnostic potential when compared to the pattern (cultural). The second article compared to CRP and PCT. For this, there were two articles of a systematic review and meta-analysis. The first article compared the accuracy in determining bacterial infection in immunosuppresses of CRP to the gold standard (cultures). Our first review included 1,418 patients and showed good accuracy of CRP as a biomarker for the diagnosis of bacterial infection presenting a sensibility of 69% and 76% specificity with an area under the curve (AUC) 0.77. The results are similar to those found in the literature for immunocompetent,(3) sensitivity 75%, specificity of 67% and Area Under the Receiver Operating Characteristic Curve (AUROC): 0.92. When the PCT was compared with PCR, both biomarkers showed a moderately accurate for use as tool diagnostic bacterial infection with a Odds ratio diagnostic (DOR) 7.24 (95% CI (2.83-14.60) and PCT to 5:56 (95% CI (5.21-10.30) for CRP. the PCT and CRP had a sensitivity of 69% and 68% and a specificity of 75% and 71%, respectively. Both showed similar results may be used in the diagnosis of sepsis in immunosuppression.

Sepsis is a worldwide health problem with an enormous economic burden and devastatingly high mortality rate. The pathophysiology and immune dysfunctions that occur during sepsis remain largely unknown, severely limiting current treatment options for sepsis. Both the innate and adaptive parts of the immune system are known to be involved in the dysfunctions that occur during sepsis. Over the last few years adenosine has been recognized as an endogenous mediator that alters both innate and adaptive immune responses. Adenosine receptors are largely expressed on many different immune cells and may serve to limit excess collateral damage in the setting of inflammation. In this study, the pharmacological effects of an A2A receptor antagonist on septic mice were examined using the CLP model of sepsis that results in a polymicrobial infection. Pharmacological inactivation of the A2A receptor significantly increased mortality in septic mice predicted to live in comparison to those given only vehicle. Treatment with the A2A receptor antagonist also increased expression of CD40, part of a pathway well known for its roles in inflammation. Our data also showed increased monocyte MHCII expression after treatment with an adenosine antagonist. Our data support the role that A2A receptors are involved in the immune response to sepsis, and that these receptors may serve to damage excess collateral damage ensuing from the host immune response, and that additional studies on adenosine and its related purine nucleosides would be of use for better understanding of the immune dysfunctions that occur during sepsis and other diseases.

Thesis (M.Sc.Eng.) / Sepsis is a serious medical condition in which a person becomes infected with bacteria in his or her bloodstream. The symptoms of sepsis are a result of the immune system’s interaction with the infecting agent. Currently, to diagnose a patient with sepsis, a blood sample must be collected and cultured for 24-48 hours before the infection can be confirmed. In the meantime, a broad-scope antibiotic is administered which may or may not be effective in treating the patient. If the antibiotic is ineffective, a different antibiotic must be chosen. When the results of the blood culture are available, a narrow scope antibiotic, appropriate to treat the infection is administered. However, sepsis has a mortality rate of 18-30% depending on the infecting agent and the treatment is highly time sensitive. Within 24 hours, the syndrome may progress to septic shock and mortality rates reach 50%. Therefore, it is important to quickly and correctly identify the infecting agent and provide immediate targeted treatment. Surface Enhanced Raman Spectroscopy (SERS) can be used to quickly identify and distinguish between different bacterial strains; however it requires higher bacterial concentrations than are present in the blood during the early stages of sepsis. A microfluidic evaporator chip has been developed to concentrate bacteria samples from 4μl to 100nl; the chip has been evaluated for concentration efficiency on Escherichia coli and methicillin-sensitive Staphylococcus aureus. Various blocking methods using bovine serum albumin (BSA) have been tested to reduce bacterial adhesion to the chip and have improved bacterial recovery to around 70% for both strains tested. Ongoing tests are being performed to improve bacterial recovery and sample purity for identification. / 2031-01-01

Introdução: A sepse grave é responsável por 20% das admissões em Unidades de Terapia Intensiva (CTI) sendo a maior causa de morte não cardíaca nas CTIs. Pacientes sépticos frequentemente requerem ventilação mecânica e a falha de desmame está associada ao aumento da mortalidade. Entretanto, não estão bem estabelecidas as diferenças entre sepse e não sepse quanto à ventilação mecânica, nem tampouco quanto à falha de extubação. Objetivo: Comparar a incidência de falha de extubação entre indivíduos admitidos em unidades de terapia intensiva com ou sem o diagnóstico de sepse. Design: Estudo clínico prospectivo observacional. Pacientes: Pacientes de três CTIs de Porto Alegre, Brasil foram arrolados no período de janeiro de 2004 a dezembro de 2008. Os pacientes deveriam ter idade igual ou maior a 17 anos e terem permanecido em ventilação mecânica por tempo maior que 24hs. Gestantes, traqueostomizados e pacientes que falharam no teste de ventilação espontânea (SBT) ou que não fossem extubados após seis horas do SBT foram excluídos do estudo. Material e Métodos: Pacientes com sucesso no SBT foram extubados e acompanhados por 48hs. Os dados coletados incluem parâmetros ventilatórios, gasometria arterial, radiografia de tórax e índices preditivos de desmame (f/VT, MIP, MEP, PaO2/FiO2, f, e VT) durante a VM e no 1o e 30º minutos do SBT. Resultados: 474 pacientes foram arrolados ao total. A média de idade foi de 57.9 ± 19.1 e a maioria eram homens (52.32%). A falha de extubação (FE) ocorreu em 105 pacientes (22.2%). Pacientes com sepse tiveram maior taxa de falha de extubação (27% vs 18.7%; p = 0.009) e maior tempo de permanência na CTI (16.0 ± 16.7 vs. 12.0 ± 25.0 dias; p = 0.02). Conclusão: Indivíduos internados em CTI em Ventilação Mecânica devido à sepse apresentam maior risco de falha de extubação e maior tempo de permanência na CTI que pacientes não sépticos. Estes achados justificam a realização de estudos visando a identificação de fatores associados a falha de extubação na sepse. / Introduction: Severe sepsis accounts for 20% of all admissions to intensive care unit (ICU) and is the leading cause of death in non-cardiac ICU. Septic patients often require mechanical ventilation and failure of weaning is associated with increased mortality. Nevertheless, it is not well established if there are differences between sepsis or no sepsis reasons for mechanical ventilation (MV) nor chances of extubation. Objective: To compare the influence of the diagnosis of sepsis on the incidence of extubation failure in patients admitted to intensive care units with or without the diagnosis of sepsis. Design: prospective observational clinical study. Patients: Patients were consecutively enrolled at three ICU from Porto Alegre, Brazil from January, 2004 till December, 2008 if they were 17 years or older, on mechanical ventilation for a period greater than 24 hours and. Pregnant, tracheostomized and patients who failed spontaneous breathing trial (SBT) or who were not extubated after six hours of SBT were excluded from the study. Methods and measurements: Patients with successful SBT were followed for 48 hours. Data collection included ventilation parameters, arterial blood gas examination, thorax radiograph and the weaning indexes (f/VT, MIP, MEP, PaO2/FiO2, f, and VT) during MV in the 1st and 30th minutes of SBT. Results: A total of 474 patients were enrolled. The mean age was 57.9 ± 19.15 and most was men (52.32%). Overall, Extubation Failure (EF) occurred in 105 (22.2%). Patients with sepsis had a higher rate of extubation failure (27% vs 18.7%, p = 0.009) and stayed longer at the ICU (16.0 ± 16.7 vs. 12.0 ± 25.0 days, p = 0.02). Conclusion: Individuals at ICU on Mechanical Ventilation due to sepsis are at higher risk of failure of extubation than no septic individuals. These findings justify conducting studies aimed at identifying factors associated with extubation failure in sepsis.