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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
161

Estudo comparativo entre dois protocolos de profilaxia antibiótica em procedimentos odontológicos realizados em pacientes imunossuprimidos / Comparative study between two regimens of antimicrobial prophylaxis in dental invasive procedures in immunosuppressed patients

Diana Rosado Lopes 11 August 2009 (has links)
Estudos sobre profilaxia antibiótica em pacientes imunossuprimidos submetidos a procedimentos cruentos odontológicos são bastante escassos, no entanto já existe um consenso de que estes pacientes são sabidamente de risco para infecção de sítio cirúrgico odontológico e que, portanto, necessitam de profilaxia antibiótica. Não é definido, no entanto, o regime profilático ideal para estes pacientes. O objetivo deste estudo é comparar a duração de antibioticoprofilaxia através de dois esquemas para prevenção de infecção após procedimentos odontológicos cruentos em pacientes imunossuprimidos transplantados renais ou hepáticos e em pacientes imunossuprimidos por quimioterapia. Este ensaio clínico foi randomizado e avaliou pacientes consecutivos com neoplasia e que fizeram uso de quimioterapia anti-neoplásica no último mês e pacientes transplantados de órgãos sólidos com medicação imunossupressora anti-rejeição, que necessitavam de exodontia e/ou raspagem periodontal como tratamento odontológico. O atendimento foi realizado na Divisão de Odontologia do Hospital das Clínicas da Faculdade Medicina da Universidade de São Paulo e foram incluídos pacientes da rotina do ambulatório que atendiam aos critérios de inclusão para participarem do protocolo da pesquisa e que concordaram em participar, assinando o Termo de Consentimento Livre e Esclarecido. Os pacientes foram randomizados para um dos dois grupos de regime profilático (grupo 1 - uma cápsula de 500mg de amoxicilina duas horas antes do procedimento odontológico; grupo 2 duas cápsulas de 500mg de amoxicilina, sendo a primeira duas horas antes do procedimento e a segunda oito horas após a primeira) e realizaram exame de sangue para avaliação da cultura hematológica após a realização do procedimento, sendo acompanhados durante um mês. A amostra calculada foi de 414 pacientes, sendo 207 em cada grupo. Os dados foram analisados através do programa SPSS Windows (versão 13.0, Chicago IL) e a partir daí foi obtida uma tabela descritiva e utilizado o teste qui-quadrado para comparação das variáveis entre os dois grupos. O nível de significância foi de p< ou = 0,05. Foi realizada também uma análise multivariada. A amostra foi analisada durante o período de novembro de 2006 a novembro de 2007. Não ocorreram os seguintes desfechos: infecção do sítio cirúrgico, antibiótico introduzido pelo médico no pós-operatório em até 30 dias após o procedimento odontológico e morte até o 15º dia após o procedimento odontológico. Os desfechos encontrados foram: necessidade de tomar analgésico após o 3º dia e até o 15º dia após o procedimento (3 no grupo 1 e 1 no grupo 2) e internação hospitalar até o 15º dia após o procedimento (2 no grupo 1 e 1 no grupo 2). A análise multivariada não alterou os resultados. Este estudo não demonstrou uma diferença entre utilizar uma ou duas doses de amoxicilina como profilaxia em procedimentos invasivos dentários em pacientes imunosuprimidos / Studies about antibiotic prophylaxis in immunosuppressed patients submitted to odontological invasive procedures are scarse, however there is already a consensus that these patients are in risk for post-operative infection in dentistry and that, therefore, they need antibiotic prophylaxis. It is not defined, however, the best prophylactic regimen for these patients. The aim of this study was to compare two regimens of antimicrobial prophylaxis in dental invasive procedures in immunosuppressed patients by chemotherapy for cancer or solid organ transplants. This is a randomized controlled study and it evaluated consecutive patients with cancer and that were submitted to chemotherapy in the last month and solid organ transplanted patients who needed exodontia or periodontal scaling and root planning as odontological treatment. This study was done in the Divisão de Odontologia of Hospital das Clínicas of Faculdade Medicina of the Universidade de São Paulo and it was included patients from the routine of the ambulatory who presented all the inclusion criteria and signed the informed consent. Patients were randomly assigned to one of the groups of prophylactic regimens (group 1 amoxicillin 500mg administered orally two hours before the procedure; group 2 amoxicillin 500mg administered orally two hours before the procedure and a second dose eight hours later) and had blood sample collected for culture immediately after the procedure, being followed up for one month. The total sample size was of 414 patients, being 207 in each group. Data were analyzed using the software SPSS Windows (version 13.0, Chicago IL). The characteristics of the patients of the 2 groups were compared using the chi-square test. The two groups were compared as to each outcome. A multivariate analysis was performed evaluating the groups as to the occurrence of any of the outcomes, by multiple logistic regression. The sample was evaluated between november of 2006 and november of 2007. The following outcomes did not occur: surgical site infection; systemic use of an antimicrobial drug within 30 days after the procedure and death by any reason within 15 days after the procedure. The other outcomes were: use of medication against pain after 3rd day after the procedure (three in group 1 and one in group 2) and hospitalization for any reason within 15 days after the procedure (two in group 1 and one in group 2). The multivariate analyses did not alter the results. This study did not demonstrate a difference between using one or two doses of amoxicillin as prophylaxis in invasive odontological procedures in immunosuppressed patients
162

ADESÃO À TERAPIA IMUNOSSUPRESSORA EM TRANSPLANTADOS RENAIS / ADHERENCE TO IMMUNOSUPPRESSIVE THERAPY IN RENAL TRANSPLANT

Morais, Regina de Fátima Cruz de 15 August 2013 (has links)
Made available in DSpace on 2016-08-19T17:47:15Z (GMT). No. of bitstreams: 1 Dissertacao Regina.pdf: 270348 bytes, checksum: 110159b677af4fdf1a5907600977940b (MD5) Previous issue date: 2013-08-15 / Introduction: Adherence to immunosuppressive therapy is essential for the maintenance of renal graft, however, non-adherence is a major challenge for effective long-term immunosuppressive. Objectives: To assess adherence to immunosuppressant therapy in renal transplant recipients. Methods: Cross sectional study with a quantitative approach, from May/2012 to abril/2013 with 151 kidney transplant recipients followed up at outpatient posttransplant Renal Transplant Service, University Hospital of the Federal University of Maranhão (HUUFMA). Two instruments were used for data collection. At first, we collected sociodemographic, clinical data and the dispensing of immunosuppressants. The second was the Immosupressive Therapy Adherence Scale -ITAS, to measure adherence by self-report. Adherence to immunosuppressants was assessed by self-report methods, dispensing of immunosuppressants and a combination of self-report and dispensing. At the junction of the variable compliance with the sociodemographic and clinical variables, we applied the Test t for independent samples and the Mann-Whitney for variables without normal. For comparisons of categorical data were used the Chi-Square test. Analyzed the Kappa coefficients to verify the agreement between the methods for evaluating adherence. Considered significant if the p-value below 0.05. Results: Of the 151 transplants, 51.7% were male, 74.8% color/mulatto, 55.7% married, 58.9% were inactive with family income above minimum wage 77.5%, more than 8 years were 62.9% and the average age was 40.33 ± 11, 7 years. Was found a percentage of non-adherence (60.3%) by self-report, (71.5%) by dispensing of immunossuppressive and (37,1%) by combination of by self-report and dispensing of immunossuppressive. Variables that had significant associations with nonadherence were: being transplanted living donor (p = 0.03), younger age (p = 0.04) and the type of immunosuppressive agent used (p = 0.04). higher levels of creatinine were found in the non bonded by self-report (p = 0.04) and membership combined (p = 0.02). Conclusions: poor adherence to immunosuppressive therapy found in this series is an important risk factor for adverse clinical outcomes such as chronic rejection and graft loss. / Introdução: A adesão à terapia imunossupressora é fundamental para a manutenção do enxerto renal, no entanto, a não adesão representa um grande desafio para a eficácia imunossupressora em longo prazo. Objetivos: avaliar adesão à terapia imunossupressora em transplantados renais. Metodologia: estudo transversal, com abordagem quantitativa, no período de maio/2012 a abril/2013, com 151 transplantados renais em acompanhamento no ambulatório de pós-transplante do Serviço de Transplante Renal do Hospital Universitário da Universidade Federal do Maranhão (HUUFMA). Foram utilizados dois instrumentos para a coleta dos dados. No primeiro, foram coletadas as variáveis sociodemográficas, clínicas e dados da dispensação dos imunossupressores. O segundo foi a Escala de Aderência à Terapia Imunossupressora (Immosupressive Therapy Adherence Scale (ITAS), para mensurar a adesão pelo autorrelato. A adesão aos imunossupressores foi avaliada pelos métodos autorrelato, dispensação dos imunossupressores e uma combinação de autorrelato e dispensação. No cruzamento da variável adesão com as variáveis sociodemográficas e clínicas, aplicou-se o Teste t para amostras independentes e o Mann-Whitney em variáveis sem normalidade. Para comparações de dados categóricos foram utilizados o teste Qui- Quadrado. Analisou-se o coeficiente de Kappa para verificar a concordância entre os métodos de avaliação de adesão. Considerou-se significante o p-valor abaixo de 0,05. Resultados: Dos 151 transplantados, 51,7% eram masculinos, 74,8% de cor/raça parda, 55,7% casados, inativos foram 58,9%, com renda familiar acima de um salário mínimo 77,5%, mais de oito anos de estudo foram 62,9% e a média de idade foi de 40,33 ± 11,7 anos. Encontrou-se um percentual de não adesão de (60,3%) no autorrelato e (71,5%) na adesão combinada. As variáveis que tiveram associações significativas com a não adesão foram: ter sido transplantado com doador vivo (p= 0,03), idade mais jovem (p=0,04) e tipo de imunossupressor usado (p=0,04). Níveis mais elevados de creatinina foram encontrados no grupo não aderente pelo autorrelato (p=0,04) e adesão combinada (p=0,02). Conclusão: a baixa adesão a terapia imunossupressora encontrada nesta casuística é um importante fator de risco para desfechos clínicos negativos, como rejeição crônica e perda do enxerto.
163

Avaliação do peptídeo sintético (P10): associado ao tratamento quimioterápico em camundongos BALB/c anérgicos infectados com Paracoccidioides brasiliensis. / Assessment of synthetic peptide (P10): associated with chemotherapy treatment in BALB/c mice infected with Paracoccidioides brasiliensis.

Julian Esteban Muñoz Henao 21 February 2013 (has links)
A paracoccidioidomicose (PCM), doença sistêmica de caráter granulomatoso, é causada pelo fungo termodimórfico Paracoccidioides brasiliensis (Pb). A gp43 secretada pelo Pb, possui um trecho específico de 15 aminoácidos designado como (P10), é reconhecido por linfócitos T. No presente trabalho, avaliamos a ativação da resposta imune e o efeito aditivo da imunização com o peptídeo P10, em camundongos induzidos à imunossupressão com dexametasona. Os resultados indicam um efeito aditivo da imunização com P10 e o tratamento com as drogas em camundongos BALB/c imunossuprimidos e infectados; associado a redução da carga fúngica no pulmão, baço e fígado desses animais, detectamos aumento de citocinas proinflamatorias, no homogenato de pulmão e no sobrenadante de cultura celular. Animais imunossuprimidos e imunizados com P10 apresentaram um aumento significativo na produção de Óxido Nítrico (NO). A eficiencia na resposta levou a um aumento na sobrevida de 100%. Estes resultados sugerem que o P10, representa uma alternativa promisoria na geração de uma vacina anti-PCM. / Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by Paracoccidioides brasiliensis (Pb). The gp43 secreted by Pb has a 15-mer peptide designated as P10 that is recognized by T lymphocytes. In the present work we evaluated the activation of immune response and the additive effect of P10 immunization in BALB/c mice induzed to immunossupression with Dexamethasone. Results indicate an additive effect of P10 immunization and the treatment with drugs in BALB/c mice immunosuppressed and infected; associated with a significant reduction in fungal burden in the lung, spleen and liver of these animals. Also, we detected an increase of proinflammatory cytokines such as IFN-<font face=\"symbol\">g, TNF-<font face=\"symbol\">a e IL-12, in lung homogenates and cell culture supernatant. Immunosuppressed animals that were immunized with P10 showed an increase in the Nitric Oxide production. The efficiency of response led to a 100% survival in animals immunized with P10 and treated with antifungal drugs. Our results suggest that P10 represents a promising alternative of anti-PCM vaccine generation.
164

Avaliação da monitorização da terapia com anticorpos policlonais antilinfócitos T em transplante renal : contagem linfocitária total e de células T CD3+ no sangue periférico

Machado, Fabiani Palagi January 2016 (has links)
Introdução: A globulina anti-timocitária (ATG) é um anticorpo policlonal depletor de linfócitos amplamente utilizado no transplante de órgãos. O monitoramento deste agente em receptores de transplante renal pode ser realizado por contagem de linfócitos totais e células T CD3+ no sangue periférico. Objetivo: Avaliar a correlação entre estas duas formas de monitorização. Métodos: Estudo retrospectivo, centro único, avaliou 226 pacientes que receberam enxerto renal entre 2008 e 2013 e que foram tratados com ATG para terapia de indução ou para tratamento de rejeição celular aguda grave. A primeira dose foi administrada no intra-operatório e as subsequentes de acordo com os níveis de células T CD3+ ou número de linfócitos totais no sangue periférico. Os coeficientes de correlação e concordância foram avaliados em amostras pareadas. Resultados: No total 664 amostras pareadas foram analisadas para o número de linfócitos totais e células T CD3+. O coeficiente de correlação de Spearman enre os resultados foi 0.416 (P <0.001) para a amostra geral, 0.435 (P < 0.001) para os pacientes em indução e 0.285 (P<0.005) para os pacientes em tratamento de rejeição. O coeficiente de concordância Kappa entre as amostras gerais foi 0.267 (P < 0.001), 0.280 (P < 0.001) para indução e 0.155 (P<0.081) para pacientes em tratamento. Os parâmetros diagnósticos para a contagem de linfócitos totais foram calculados usando o número de células T CD3+ como padrão-ouro com o ponto de corte de > 20 células/mm³. Na curva ROC o melhor ponto (256 linfócitos/mm3) apresenta área sobre a curva de 0.71 (95% CI: 0.67-0.75) com sensibilidade de 66.8%, especificidade 66.5%, valor preditivo positivo 46.6% e valor preditivo negativo 82.1%. Conclusão: Baseados nestes resultados consideramos que a monitorização da administração e do intervalo das doses de ATG deva ser realizada através da contagem de células T CD3+, por citometria de fluxo, em detrimento dos linfócitos totais no sangue periférico. / Background: Anti-thymocyte globulin (ATG) is a preparation of depleting antibodies largely utilized in organ transplantation. The monitoring of this agent in renal transplant recipients can be accomplished by counting total lymphocytes and CD3+T cells in the peripheral blood. Objective: Evaluated the correlation between these two measurements. Methods: Retrospective study, single center study that evaluated 226 patients who received a kidney graft between 2008 and 2013 and where treated with ATG either for induction therapy or for treatment a severe acute cellular rejection. The first dose was given intra-operatively and subsequent doses were administered according to the levels of CD3+ T cells or number of total lymphocytes in the peripheral blood. Correlation and concordance coefficients were evaluated in paired samples. Results: A total of 664 paired samples were analyzed for the number of lymphocytes and CD3+ T. The Spearman’s correlation coefficient between the results was 0.416 (P < 0.001) to all samples, 0.435 (P < 0.001) for induction therapy samples and 0.285 (P<0.005) for therapeutic samples. The Kappa’s concordance coefficient between samples was 0.267 (P < 0.001) to all samples, 0.280 (P < 0.001) for induction therapy samples and 0.155 (P<0.081) for therapeutic samples. The diagnostic parameters for the total lymphocyte counting were calculated using number of CD3+ T cells as the gold standard at the cut off at > 20 cells/mm³. At the ROC curve using the best cut off (256 lymphocytes/mm3) an AUC of 0.71 (95% CI: 0.67-0.75) was found along with a sensitivity 68.8%, specificity 66.5%, positive predictive value 46.6% and negative predictive value 82.1%. Conclusion: Based upon these results it is not possible to reliably replace the flow cytometric assay for CD3+ T cells by the counting of total lymphocytes in the peripheral blood in the monitoring of ATG administration in kidney transplant recipients.
165

Investigation of novel therapeutic strategies in B cell and antibody mediated disease

Banham, Gemma January 2019 (has links)
Terminally differentiated B cells are responsible for antibody generation, a key component of adaptive immunity. IgG antibodies play an important role in defence against infection but can be pathogenic in some autoimmune diseases and in solid organ transplantation. In addition to antibody generation, there is increasing interest in the antibody-independent functions of B cells, including their ability to regulate immune responses via the production of IL10. In this thesis I firstly explored the therapeutic potential of belimumab, an anti-BLyS antibody, in an experimental medicine study in kidney transplant recipients. The rationale for this study was based on published studies showing that B cells activate alloreactive T cells and secrete human leukocyte antigen (HLA) and non-HLA antibodies that negatively affect graft function and survival, but may also play a protective role by regulating alloimmune responses promoting transplant tolerance. B-Lymphocyte Stimulator (BLyS) is a cytokine that promotes B cell activation and survival. We performed the first randomized controlled trial using belimumab as early maintenance immunosuppression in kidney transplantation. In belimumab-treated subjects, we demonstrate a reduction in naïve and activated memory B cells, plasmablasts, IgG transcripts in peripheral blood and new antibody formation as well as evidence of reduced CD4 T cell activation and of a skewing of the residual B cell compartment towards an IL10-producing regulatory phenotype. This experimental medicine study highlights the potential of belimumab as a novel therapeutic agent in transplantation. In the second part of my project I performed a preclinical study investigating the potential efficacy of bromodomain inhibitors in reducing antibody-mediated immune cell activation. Immune complexed antigen can activate mononuclear phagocytes (MNP), comprising macrophages and dendritic cells (DCs), via ligation of Fc gamma receptors (FcγR), that bind the Fc region of IgG. FcγR-dependent MNP activation results in profound changes in gene expression that mediate antibody effector function in these cells. The resulting inflammatory response can be pathological in the setting of autoimmune diseases, such as systemic lupus erythematosus and in antibody-mediated rejection in transplantation. BET proteins are a family of histone modification 'readers' that bind acetylated lysine residues within histones and function as a scaffold for the assembly of complexes that regulate gene transcription. Bromodomain inhibitors (I-BET) selectively inhibit the transcription of a subset of inflammatory genes in macrophages following toll-like receptor stimulation. Since MNPs make a key contribution to antibody-mediated pathology, we sought to determine the extent to which I-BET inhibits macrophage and DC activation by IgG. We show that I-BET delays phagolysosome maturation associated with build-up of immune complex (IC) whilst selectively inhibiting IC induced cytokine production. I-BET changed MNP morphology, resulting in a less adherent phenotype, prompting an assessment of its impact on DC migration. In vitro, in a three-dimensional collagen matrix, IgG-IC induced augmentation of DC chemotaxis to chemokine (C-C motif) ligand 19 (CCL19) was abrogated by the addition of I-BET. In vivo, two photon imaging showed that systemic I-BET treatment reduced IC-induced dermal DC mobilisation. Tissue DCs and transferred DC also had reduced migration to draining lymph nodes following I-BET treatment. These observations provide mechanistic insight into the potential therapeutic benefit of I-BET in the setting of antibody-associated inflammation.
166

Studies of Rejection in Experimental Xenotransplantation

Lorant, Tomas January 2002 (has links)
<p>One main hurdle to xenotransplantation, i.e. transplantation between different species, is the immunological barrier that the organ meets in the recipient. The aim of this thesis was to characterise xenogeneic rejection mechanisms by using the concordant mouse-to-rat heart transplantation model.</p><p>Graft-infiltrating immune cells could be isolated from both rejecting and non-rejecting grafts using ex vivo propagation, a technique based on incubation of graft biopsies in culture medium for 48 hours. The numbers of recovered T lymphocytes were considerably higher in grafts undergoing cell-mediated rejection than in grafts undergoing acute vascular rejection (AVR) or in non-rejecting transplants. Thus, ex vivo propagation should be a valuable tool for further studies of cell-mediated rejection.</p><p>Cytokine patterns in the grafts, as measured by a quantitative real-time RT-PCR method, showed that AVR and cell-mediated rejection are associated with an increase of both pro-inflammatory cytokines (IL-1β and TNF-α) and more specific cytokines (IL-2, IL-10, IL-12p40 and IFN-γ). These data differed considerably from the patterns seen in the spleens of the recipients. Cell-mediated xenograft rejection was also found to be associated with a local accumulation of hyaluronan.</p><p>Oral administration of xenogeneic cells stimulated a production of antibodies that could induce hyperacute rejection of cardiac xenografts when passively transferred to graft recipients. This is in contrast to several models for autoimmune diseases and allogeneic transplantation where oral administration of antigens is an effective way to induce unresponsiveness. Hence, future attempts to induce oral tolerance in xenotransplantation should be done with caution.</p>
167

The mechanism study of novel approaches to control chronic allograft rejection in rat orthotopic small bowel transplantation

Li, Xiaosong, January 2006 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.
168

Studies of Rejection in Experimental Xenotransplantation

Lorant, Tomas January 2002 (has links)
One main hurdle to xenotransplantation, i.e. transplantation between different species, is the immunological barrier that the organ meets in the recipient. The aim of this thesis was to characterise xenogeneic rejection mechanisms by using the concordant mouse-to-rat heart transplantation model. Graft-infiltrating immune cells could be isolated from both rejecting and non-rejecting grafts using ex vivo propagation, a technique based on incubation of graft biopsies in culture medium for 48 hours. The numbers of recovered T lymphocytes were considerably higher in grafts undergoing cell-mediated rejection than in grafts undergoing acute vascular rejection (AVR) or in non-rejecting transplants. Thus, ex vivo propagation should be a valuable tool for further studies of cell-mediated rejection. Cytokine patterns in the grafts, as measured by a quantitative real-time RT-PCR method, showed that AVR and cell-mediated rejection are associated with an increase of both pro-inflammatory cytokines (IL-1β and TNF-α) and more specific cytokines (IL-2, IL-10, IL-12p40 and IFN-γ). These data differed considerably from the patterns seen in the spleens of the recipients. Cell-mediated xenograft rejection was also found to be associated with a local accumulation of hyaluronan. Oral administration of xenogeneic cells stimulated a production of antibodies that could induce hyperacute rejection of cardiac xenografts when passively transferred to graft recipients. This is in contrast to several models for autoimmune diseases and allogeneic transplantation where oral administration of antigens is an effective way to induce unresponsiveness. Hence, future attempts to induce oral tolerance in xenotransplantation should be done with caution.
169

Wahrnehmung empfohlener Schutzimpfungen bei Patienten mit Morbus Crohn und Colitis ulcerosa / Adherence to vaccination recommendations in patients with inflammatory bowel diseases

Tiedemann, Astrid 29 October 2012 (has links)
Hintergrund: Patienten mit chronischen entzündlichen Erkrankungen sind aufgrund ihrer Grundkrankheit, aber auch durch die häufig notwendige immunsuppressive Therapie gefährdet, an einer impfpräventablen Infektionskrankheit zu erkranken. In einer Stichprobe sollte der Impfstand bei Patienten mit chronisch-entzündlichen Darmerkrankungen (CED) erhoben werden. Besondere Beachtung galt Vorbehalten der Patienten gegen die empfohlenen Schutzimpfungen. Methoden: Wir baten 203 Patienten mit CED (davon 57% Mb. Crohn, 63% weiblich; medianes Alter 36 Jahre), die im letzten Jahr keine Impfberatung erhalten hatten, einen Fragebogen mit 38 Fragen zu beantworten. Zudem wurden alle Impfnachweise erfasst und mit den aktuellen Empfehlungen der Ständigen Impfkommission abgeglichen. Die Befragung erfolgte vom 1.4. bis 30.9.2009. Ergebnisse: Nur 83% der Patienten hatten einen Impfausweis. Es fanden sich erhebliche Impfdefizite; so wurden in den letzten zehn Jahren nur 67% der Patienten gegen Tetanus und 21% gegen Pertussis geimpft, 28% nahmen die Impfung gegen die saisonale Grippe 2008 wahr und nur 9% wurden jemals gegen Pneumokokken geimpft. Im Subgruppenvergleich von Patienten mit TNF-Blockern (n=39) mit denjenigen Patienten, die noch nie eine immunsuppressive Dauertherapie erhielten (n=67), zeigten sich keine Unterschiede. 80% der Patienten wären bereit, alle offiziell empfohlenen Schutzimpfungen durchführen zu lassen. 22% aller Patienten gaben an, Schutzimpfungen zu vermeiden, weil sie Nebenwirkungen befürchteten, 15% weil das Immunsystem „nicht intakt“ ist und 9% befürchten eine Verschlimmerung der CED durch eine Impfung. Schlussfolgerungen: Der Impfstand in der untersuchten Stichprobe war unzureichend. Es fand sich insbesondere eine deutliche Diskrepanz zwischen der hohen Bereitschaft der Patienten, Schutzimpfungen durchführen zu lassen, und dem tatsächlichen Impfstand. Unsere Daten legen die Notwendigkeit einer erhöhten ärztlicher Wachsamkeit für Impflücken bei immunsuppressiv behandelten Patienten nahe. / Background: Patients with chronic inflammatory diseases are at increased risk for vaccine preventable infectious diseases. This is caused by the inflammatory state itself as well as often necessary immunosuppressive therapy. In a random sample, we investigated whether patients with inflammatory bowel disease (IBD) are sufficiently vaccinated. Special attention was spent to arguments for vaccine refusal. Methods: Between 1.4.2009 and 30.9.2009, we asked 203 consecutive IBD patients (thereof 57% Crohn’s disease, 63% female; median age 36 years), who got no vaccination advise within the last year to answer a questionnaire with 38 questions. As well, the vaccination cards were adjusted with the official recommendations. Results: Only 83% of patients had a vaccination card. We recognized substantial vaccination deficiencies. Within the past 10 years, only 67% of patients had tetanus and 21% had pertussis vaccination. Only 28% had an influenza vaccination in 2008 and only 9% were ever immunized against pneumococcus. A subgroup analysis of patients with TNF-blockers (n=39) with patients, who never had immunosuppressive therapy (n=67) revealed no difference. 80% of all patients are willing to adhere to all officially recommended vaccinations. 22% and 15% of patients stated that they avoid vaccinations as they afraid side effects or as they assess their immune system as not intact. Nine per cent feared a worsening of IBD after vaccination. Conclusions: In this random sample, the adherence to vaccination recommendations was low. We observed a marked difference between the willingness of IBD patients for immunizations and the realized vaccinations. Our data suggest that an increased medical awareness for vaccination deficiencies in immunosuppressed patients is mandatory.
170

Characterizing Bladder Adaptive Immune Responses to Uropathogenic Escherichia coli Infections

Chan, Cheryl Yuen Yu January 2012 (has links)
<p>The mammalian urinary bladder is a highly specialized organ that must be able to withstand considerable amounts of osmotic pressure at its mucosal surface, in addition to maintaining an impenetrable barrier against potential pathogens. The lower urinary tract's virtually inevitable exposure to external microbial pathogens warrants efficient tissue-specialized defenses to maintain sterility. The observation that the bladder can become chronically infected with uropathogenic E.coli (UPEC) in combination with clinical observations that antibody responses following bladder infections are not detectable, suggest defects in the formation of adaptive immunity and immunological memory. We have identified a broadly immunosuppressive transcriptional program specific to the bladder, but not the kidney, during infection of the urinary tract that is dependent on tissue-resident mast cells. This mast cell-dependent phenomenon involves localized production of IL-10 and results in suppressed humoral and cell-mediated responses and bacterial persistence. Therefore, in addition to the previously described role of mast cells orchestrating the early innate immune responses in the bladder during infection, they subsequently play a tissue-specific immunosuppressive role. These findings may explain the prevalent recurrence of bladder infections and suggest the bladder as a site exhibiting an intrinsic degree of mast cell-maintained immune privilege.</p><p> Interestingly, though the bladder is not capable of initiating an effective adaptive immune response during bladder infections, we have generated data showing that it was possible to circumvent the immune limitations of the bladder to provoke a strong adaptive and protective immune response by vaccinating against UPEC at an alternate mucosal site. We reasoned that by immunizing the nasal regions of mice with a vaccine formulation comprising of FimH adhesin, a highly conserved adhesive moiety of type 1 fimbriae expressed on UPEC, and an effective mucosal adjuvant we would evoke protective immunity against UPEC infections. We found that a FimH vaccine coupled with either a mast cell activating adjuvant c48/80 or CpG oligodeoxynucleotide, a TLR9 agonist, evoked high levels of FimH specific IgG antibody in the serum and IgA in the urine of immunized mice. We also observed that following UPEC challenge, these FimH/adjuvant immunized mice exhibited significantly reduced bacterial load in the bladders compared to mice challenged with just FimH. These studies reveal that immunization of nasal regions with a FimH vaccine is an effective strategy to overcome the limitation in adaptive immunity observed in the bladder.</p> / Dissertation

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