Introdução: As Infecções no trato urinário (ITU) estão entre as doenças infecciosas mais comumente diagnosticadas e são responsáveis por uma grande proporção do consumo de agentes antimicrobianos, sendo a Escherichia coli o microorganismo mais freqüentemente envolvido. Os antimicrobianos utilizados no tratamento das ITU sofrem concentração no processo de eliminação, ocasionando altos níveis de antimicrobiano na urina. No entanto, os testes que avaliam a susceptibilidade aos antimicrobianos são baseados em concentrações séricas. Assim, é de interesse a padronização de um teste que utilize níveis urinários (discos de alta potência) dos antimicrobianos frente aos uropatógenos. Objetivo: padronizar teste de susceptibilidade aos antimicrobianos para E. coli de ITU, com concentrações de antimicrobianos atingidas na urina. Métodos: foram utilizados 204 isolados bacterianos resistentes a pelo menos um dos seguintes antimicrobianos: ampicilina, cefalotina, ciprofloxacino, gentamicina, sulfametoxazol-trimetoprima(cotrimoxazol) para os quais foi determinada a MIC através de diluição em agar. Através da análise das MIC obtidas e das concentrações que os antimicrobianos atingem na urina, foram estabelecidas as concentrações dos discos de alta concentração. As seguintes concentrações de disco foram utilizadas: ampicilina (500, 400, 300 μg), cefalotina (200, 100 μg) e ciprofloxacino (200, 150 μg). Resultados: a ampicilina apresentou MIC ≥ 512μg/mL para cerca de 50% dos isolados. Dos discos testados, o de 500 μg mostrou melhor coeficiente de correlação de Spearman (rs: -0,659) e foi escolhido para a determinação do ponto de corte através de curva ROC (receiver operating characteristic). Pela curva, um diâmetro de halo de 9 mm separaria as amostras resistentes (R) das susceptíveis (S) a altos níveis de ampicilina com 100% de sensibilidade e especificidade de 50%. A cefalotina apresentou MIC inferior a 256μg/mL para 78% dos isolados sendo que o “rs” para os discos de 100 e 200 μg foi o mesmo: -0,744. Pela curva ROC, halos de 17mm (disco de 200μg) e 13mm (disco de 100μg) discriminariam amostras R de S com 100% de sensibilidade e 96,9% de especificidade. O ciprofloxacino apresentou MIC ≤ 128 μg/mL para mais de 50% dos isolados, sendo que o “rs” foi melhor com o disco de 200μg (rs:-0,916). Um halo de 21mm separaria as amostras S e R com 100% de sensibilidade e 78,9% de especificidade. Para o cotrimoxazol, 95% das amostras se mostraram resistentes a altos níveis e os testes com disco de alta potência não foram realizados. Para a gentamicina o baixo nº de amostras (n=22) prejudicou a análise, mas cerca de 63% dos isolados seriam susceptíveis a altos níveis. Conclusão: O presente estudo demonstrou que o uso de discos de alta concentração pode ser útil para avaliar a susceptibilidade de isolados urinários. Isto tem importância em laboratórios clínicos onde, embora haja dificuldade na realização da MIC, testes de disco-difusão estão incorporados na rotina. / Introduction: The urinary tract infections (UTI) are among the most common infectious diseases and are responsible for a high antimicrobial usage. The Escherichia coli is the main microorganism involved in UTI. The antimicrobials used for treatment of UTI concentrate in the urinary tract and this leads to high levels of them in the urine. However, the susceptibility tests are based on the serum levels of the antimicrobials. Therefore, it is of interest to develop a test which correlates the urinary levels of antibiotics (discs with high levels) with the uropathogens. Objective: to propose a susceptibility test of E. coli from UTI using doses of the antimicrobials reached in the urine. Methods: a total of 204 clinical isolates of E.coli resistant, according to conventional antimicrobial susceptibility test to, at least, one of the following antimicrobials: ampicillin, cefalotin, ciprofloxacin, gentamicin and trimetoprima- sulfametoxazol. The MIC was determined by the agar dilution technique. According to the results of the MICs and the urinary levels of the antimicrobials it was possible to establish the concentration of the high potency discs. The following concentration of discs were used: ampicilina (500, 400, 300 μg), cefalotin (200, 100 μg) and ciprofloxacin (200, 150 μg). Results: ampicillin presented MIC ≥ 512μg/mL for around 50% of E. coli isolates. The disc containing 500 μg of ampicillin displayed the best coeficient of correlation (rs: -0,659) and it was chosen to establish diameter breakpoint according to the ROC curve. A diameter of 9 mm would discriminate high level ampicillin resistant isolates with 100% and 50% of sensitivity and specificity, respectively. Cefalotin presented MIC below 256 μg/mL for 78% of E. coli isolates. Its “rs” for discs containing 100 and 200μg was the same: - 0,744. According to the ROC curve zone diameters of 17mm (disk of 200μg) e 13mm (disk of 100μg) were able to discriminate isolates resistant with 100% and 96.9% of sensitivity and specificity, respectively. Ciprofloxacin presented MIC ≤ 128 μg/mL for more than 50% of isolates and the best “rs” was achieved with the 200μg (r:-0,916) disk. A zone diameter of 21mm would discriminate susceptible isolates with 100% and 78.9% of sensitivity and specificity. respectively. A total of 95% of E. coli isolates proved to be resistant to high levels of cotrimoxazole and, therefore, tests with high potency disks were not performed. Due to the small numbers of isolates resistant to gentamycin (n=22) we were not able to perform further analysis although 63% of E coli isolates proved to be susceptible to high levels of this antimicrobial. Conclusion: This study indicated that the susceptibility test with disks containing high levels of antimicrobials may be useful to evaluate the susceptibility of urinary tract isolates This may be of importance as the clinical laboratory may not be able to perform the MIC test for routine isolates.

Orientador: Carlos Arturo Levi D'Ancona / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-15T00:55:50Z (GMT). No. of bitstreams: 1 Lucio_AdeliaCorreia_M.pdf: 799763 bytes, checksum: 10002aa43f001ae9f0e6a4cc76073dc6 (MD5) Previous issue date: 2009 / Resumo:Objetivos: O objetivo do presente estudo é avaliar a eficácia dos exercícios do assoalho pélvico no tratamento dos Sintomas de Trato Urinário Inferior (STUI) em mulheres com Esclerose Múltipla (EM) e sua consequência na Qualidade de Vida (QV). Métodos: Foi realizado um ensaio clínico prospectivo, randomizado e cego. Vinte e sete mulheres com diagnostico de EM e STUI foram divididas em dois grupos: grupo tratamento (N=13) e grupo placebo (N=14). As avaliações incluíram: avaliação do grau de comprometimento neurológico através da Escala Expandida do Estado de Incapacidade em Esclerose Múltipla - EDSS, avaliação dos STUI através do Questionário para a Avaliação de Bexiga Hiperativa - OAB-V8, avaliação da Qualidade de Vida através dos questionários SF-36, ICIQ-SF e Qualiveen. Teste do Absorvente de 24-horas, diário miccional de 3 dias, avaliação da função da musculatura do assoalho pélvico de acordo com o esquema PERFECT e Estudo Urodinâmico. As sessões de fisioterapia foram realizadas duas vezes na semana pela mesma fisioterapeuta por um período de 12 semanas em ambos os grupos. O grupo tratamento realizou exercícios do assoalho pélvico com assistência de um perineômetro e instruções para praticar os exercícios diariamente em casa. No grupo placebo um perineometro foi introduzido na vagina e nenhuma contração foi solicitada. Os dados foram coletados antes e após o tratamento. Resultados: Ao fim do tratamento, o grupo tratamento apresentou diferenças significantes de acordo com o tempo nos escores de OAB-V8 (p < 0.0001), domínio de Dor do SF-36 (p = 0.0013), ICIQ-SF (p < 0.0001) e nos domínios da QV geral (p = 0.0185) e impacto dos problemas urinários na QV (p = 0.0013) do questionário Qualiveen. Houve diminuição do peso dos absorventes (p < 0.0001), número de absorventes utilizados (p= 0.0011), nocturia (p < 0.0001) e freqüência miccional (p = 0.0348). Nos domínios do esquema PERFECT, demonstraram melhoras na força muscular (p = 0.0011), resistência (p < 0.0001), número de contrações lentas (p < 0.0001) e número de contrações rápidas (p = 0.0004). Da mesma forma, foi observado aumento do Fluxo Maximo (p = 0.0024) e diminuição do volume residual pós miccional (p = 0.0014). De acordo com o grupo, mostrou diferenças significantes nos questionários OAB-V8 (p < 0.0001), ICIQ-SF (p = 0.0003), na QV geral (p = 0.0443) e impacto dos problemas urinários na QV (p = 0.0001) do questionário Qualiveen. Foi observado redução do peso dos absorventes, (p = 0.0011), numero dos absorventes (p = 0.0159), nocturia (p < 0.0001) e melhora na força muscular (p = 0.0026), resistência (p < 0.0001), número de contrações lentas (p < 0.0001) e número de contrações rápidas (p = 0.0004) do esquema PERFECT. Nenhuma diferença foi encontrada no grupo placebo. Conclusão: Os exercícios do assoalho pélvico são efetivos no tratamento dos STUI em mulheres portadoras de EM também diminuindo o impacto na QV destas pacientes. / Abstract: Aims: The aim of the present study is to evaluate the role of Pelvic Floor Muscle Training (PFMT) in the treatment of Lower Urinary Tract Symptoms (LUTS) in women with MS and its consequence on Quality of Life (QoL). Methods: A prospective, randomized and blind clinical trial was developed. Twenty seven female patients with a diagnosis of MS and LUTS complaints were divided in two groups: treatment group (N=13) and placebo group (N=14). Evaluation included: level of neurologic disabilities by the Expanded Disability Status Scale EDSS, evaluation of LUTS through the Overactive Bladder Questionnaire - OAB-V8, the questionnaires of Quality of Life SF-36, ICIQ-SF and Qualiveen. 24-hour Pad testing, three day voiding diary, pelvic floor evaluation according to PERFECT scheme and Urodynamic study. Intervention was performed twice a week by the same physiotherapist for a period of 12 weeks in both groups. The treatment group performed PFMT with assistance of a vaginal perineometer and instructions to practice the exercises daily at home. In the placebo group a perineometer was introduced in the vagina and no contractions were required. Pre and post intervention data were recorded. Results: At the end of the treatment, the treatment group presented significant differences regarding to time in OAB-V8 scores (p < 0.0001), bodily pain domain of SF-36 (p = 0.0013), ICIQ-SF (p < 0.0001) and in GQoL (p = 0.0185) and SIUP (p = 0.0013) domains of Qualiveen questionnaire. There was a reduction of pad weight (p < 0.0001), number of Used pads (p= 0.0011), nocturia (p < 0.0001) and daytime frequency (p = 0.0348). In the PERFECT scheme there was improvement on muscle Power (p = 0.0011), endurance (p < 0.0001), resistance (p < 0.0001) and fast contractions (p = 0.0004). In the same way, it was observed a increasing of Maximum Flow Rate (p = 0.0024) and decreasing of Post Void Residual (p = 0.0014). According to group, the treatment group showed significant differences in OAB-V8 (p < 0.0001), ICIQ-SF (p = 0.0003), in GQoL (p = 0.0443) and SIUP (p = 0.0001) domains of Qualiveen. There was a reduction on pad weight (p = 0.0011), number of pads (p = 0.0159) and nocturia events (p < 0.0001) and improvement of muscle power (p = 0.0026) endurance (p < 0.0001), resistance (p < 0.0001) and fast contraction (p < 0.0001). No differences were found in placebo group. Conclusion: PFMT is an effective approach to treat LUTS in women with MS and diminish the impact of QoL in these patients. / Mestrado / Pesquisa Experimental / Mestre em Cirurgia

Orientador: Cassio Luis Zanettini Riccetto, Paulo Cesar Rodrigues Palma / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T14:43:01Z (GMT). No. of bitstreams: 1 Pereira_SimoneBotelho_D.pdf: 15194662 bytes, checksum: 0b56a80eaa780a8e384f3ce3c7c3eb80 (MD5) Previous issue date: 2008 / Resumo: Introdução e objetivos: Muitos estudos evidenciam a associação entre a gravidez e o parto e o surgimento de sintomas geniturinários. Entretanto, ainda há controvérsias sobre o papel do tipo de parto na prevenção ou no agravamento desses sintomas. Este estudo teve por objetivo comparar as alterações da contratilidade muscular do assoalho pélvico de mulheres que apresentaram três tipos diferentes de evolução do parto, além de verificar a persistência da sintomatologia miccional no puerpério tardio. Pacientes e métodos: Foram estudadas 75 primigestas com idade entre 14 e 39 anos, selecionadas dos programas de saúde da cidade de Poços de Caldas, MG - Brasil, no período de fevereiro de 2006 a fevereiro de 2008. Todas as pacientes foram avaliadas durante o último trimestre gestacional e reavaliadas no 45º ± 10 dias de puerpério. Foram investigados os sintomas miccionais pré e pós-parto através dos questionários traduzidos e adaptados culturalmente para a língua portuguesa - International Consultation on Incontinence Questionaire Overactive Bladder (ICIQ-OAB) e International Consultation on Incontinence Questionnaire ¿ Short Form (ICIQ-SF). O protocolo de avaliação do assoalho pélvico constou de: (a) Avaliação funcional dos músculos do assoalho pélvico (AFA), com graduação da contratilidade muscular em escala de zero a cinco; (b) Avaliação eletromiográfica do assoalho pélvico (EMG): realizada através de probe vaginal. Foram solicitadas três contrações máximas, voluntárias e sucessivas do assoalho pélvico. Cada contração foi gravada por 5 segundos em micro-volts (µV), com posterior análise do Root-mean-square (RMS). Utilizou-se como parâmetro de avaliação, a média aritmética do RMS das três contrações. Os testes estatísticos utilizados foram: teste exato de Fischer, teste Qui-Quadrado e a Análise de Variância ¿ ANOVA com transformação de Rank, Coeficiente de Correlação de Pearson. Resultados: As pacientes foram classificadas em três grupos de acordo com o tipo de parto: (1) Parto vaginal ¿ n=28; (2) Cesariana eletiva ¿ n=26; (3) Cesariana em vigência de trabalho de parto ¿ n=21. Houve prevalência de menor grau de escolaridade (p=0,0079) e renda familiar (p=0,0203) no grupo submetido ao parto vaginal. O grupo que realizou parto vaginal apresentou média de idade menor que o grupo de cesariana eletiva (p=0,0014), sem diferença estatística para a cesariana de urgência. Observou-se, através do ICIQ-OAB que os sintomas miccionais irritativos desencadeados durante a gestação diminuíram no período puerperal, independente do tipo de parto (p=0,0001). Entretanto, o ICIQ-SF demonstrou que os sintomas de urinários relacionados à incontinência urinária de esforço persistiram após o parto vaginal (p=0,0001). Verificou-se aumento (p=0,0306) da contratilidade muscular do grupo submetido a cesariana eletiva, durante avaliação clínica do assoalho pélvico através do AFA e diminuição (p=0,0013) da contratilidade muscular das pacientes que realizaram parto vaginal, quando avaliadas através de EMG. Foram encontrados correlações significativas entre ambos os testes de contratilidade muscular ¿ AFA e EMG. Conclusões: O parto vaginal associou-se com diminuição da contratilidade muscular do assoalho pélvico após 45 dias de pós-parto, avaliada através de eletromiografia, quando comparado ao parto cesariana eletivo ou em vigência de trabalho de parto. Os sintomas miccionais irritativos desencadeados durante a gravidez cessam no período puerperal tardio, independente do tipo de parto, porém os sintomas urinários relacionados à incontinência urinária de esforço tendem a persistir após o parto vaginal / Abstract: Introduction and objectives: Several studies evidenced the association between pregnancy and parturition and the appearance of genitourinary symptoms. However, there are still controversies about the role of the parturition type in the prevention or in the aggravation of these symptoms. This study aimed to compare the alterations of the pelvic floor muscle contractility in women who presented three different types of parturition evolution, in addition to verify the persistence of urinary symptoms in late puerperium. Patients and methods: This study comprised 75 primigravida aged 14 to 39 years, picked from health programs of the city of Poços de Caldas ¿ MG, Brazil, between February 2006 and February 2008. All patients were evaluated during the last trimester of gestation, and reevaluated in the 45th day after parturition. The pre- and postparturition urinary symptoms were investigated through the questionnaires translated and culturally adapted into the Portuguese language ¿ International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ-OAB) and International Consultation on Incontinence Questionnaire ¿ Short Form (ICIQ-SF). The protocol of pelvic floor evaluation included: (a) evaluation of pelvic floor muscle (PFM) function, with gradation of muscle contractility using a 0-5 scale; (b) electromyography (EMG) evaluation of pelvic floor performed by vaginal probe. Three maximum, voluntary and successive contractions were required from the pelvic floor. Each contraction was recorded for 5min in microvolts (µV), with posterior root-mean-square (RMS) analysis. The evaluation parameter used was the RMS arithmetic mean of the three contractions. The statistical tests used were: Fischer¿s exact test, Chi-square test, variance analysis (ANOVA) with rank transformation, and Pearson¿s correlation coefficient. Results: The patients were divided into three groups, according to the parturition type: (1) vaginal parturition ¿ n=28; (2) elective cesarean section ¿ n=26; (3) emergency cesarean section ¿ n=21. There was prevalence of lower education degree (p=0.0079) and family income (p=0.0203) in the group submitted to vaginal parturition. The group that underwent vaginal parturition presented mean age lower than the elective cesarean section group (p=0.0014), without statistical difference for emergence cesarean section. Using the ICIQ-OAB, it was observed that the irritative urinary symptoms originated from the gestation diminished during the puerperal period, independent of the parturition type (p=0.0001). However, the ICIQ-SF showed that the urinary symptoms related to effort urinary incontinence persisted after vaginal parturition (p=0.0001). It was verified increase (p=0.0306) in the muscle contractility of the group submitted to elective cesarean section during clinical evaluation of PFM function, and diminution (p=0.0013) of muscle contractility of the patients who underwent vaginal parturition, when evaluated by EMG. Significant correlations were found between both muscle contractility tests ¿ PFM function and EMG. Conclusions: Vaginal parturition was associated with reduction in the pelvic floor muscle contractility 45 days after parturition, according to electromyography evaluation, when compared with elective cesarean section or emergency cesarean section. Irritative urinary symptoms originated from pregnancy end during late puerperal period, independent of the parturition type; however, the urinary symptoms related to effort urinary incontinence tend to continue after vaginal parturition / Doutorado / Pesquisa Experimental / Doutor em Cirurgia

Para avaliar as fibras elásticas na junção vésico-uretral de ratos, em diferentes faixas etárias, realizou-se estudos histológicos, microscopia elêtronica e histomorfometria. O estudo histológico do sistema de fibras elásticas mostrou a presença dos três tipos de fibras elásticas, em todas as faixas etárias, a microscopia eletrônica de transmissão, mostrou as diferenças ultra-estruturais entre as fibras elásticas. A avaliação histomerfométrica revelou diminuição na densidade linear das fibras elásticas e oxitalânicas e aumento na das elaunínicas. Na junção vésico-uretral de animais velhos, há uma queda nas propriedades de elasticidade, recuo elástico e ancoragem, que são compensadas pelas fibras elaunínicas. O processo de envelhecimento das fibras elásticas na junção vésico-uretral não contribui sozinha e diretamente no estado de incontinência urinária, mas compensa e dá suporte a muscular, devido ao aumento das fibras elaunínicas, o que torna o sistema elástico na junção vésico-uretral indiretamente responsável pela manutenção da continência urinária. / To evaluate the elastic fibers in the junctio vesico-urethral of the rat, in different age groups, was accomplished studies histologics, electron microcopy and histomorphometrics. Study histologic showed the presence of the three types elastic fibers in all the studied age groups, electron microcopy showed the ultra-structural differences amoung elastic fibers. Histomorphometric studies revealed a decrease the linear density of the mature elastic fibers and oxytalans and an increase elaunin. In the junction vesico-urethral of the old animals there is a fall the properties elastic, elastic recoil and achorage, but they are compensated by elaunins. Processs aging of the elastic system in this place doesn?t contribute alone or directly in urinary incontinence, but it is indirectly responsible for the maintenance urinary continence.

Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2017-04-03T17:52:51Z No. of bitstreams: 1 Araujo, Fernanda Miranda de [Dissertação, 2011].pdf: 1770084 bytes, checksum: 02dc9fe25e679414ba90c97935473f41 (MD5) / Made available in DSpace on 2017-04-03T17:52:51Z (GMT). No. of bitstreams: 1 Araujo, Fernanda Miranda de [Dissertação, 2011].pdf: 1770084 bytes, checksum: 02dc9fe25e679414ba90c97935473f41 (MD5) / Objetivo. Descrever a prevalência de resistência a ciprofloxacino e analisar as variáveis potencialmente associadas a esta resistência em amostras de Escherichia coli isoladas de pacientes com câncer ginecológico e infecção do trato urinário (ITU). Métodos. Trata-se de uma série de casos de pacientes com ITU por E. coli assistidas no Hospital do Câncer II do Instituto Nacional do Câncer (INCA/HCII) de março de 2009 a fevereiro de 2010. Os casos foram detectados através de vigilância microbiológica no laboratório de bacteriologia clínica do INCA/HCII. As análises microbiológicas foram realizadas conforme recomendado pelo Clinical and Laboratory Standards Institute (CLSI). Os dados clínicos e epidemiológicos foram coletados através de revisão de prontuários. Para a avaliação das variáveis potencialmente associadas à resistência a ciprofloxacino foi feita análise multivariada por regressão logística. Resultados. Entre os 275 casos de ITU por E. coli em pacientes com câncer ginecológico incluídas no estudo, a prevalência de resistência das amostras a ciprofloxacino foi 31%. A prevalência de resistência das amostras a outros antimicrobianos como cefazolina, ceftazidima, fosfomicina, gentamicina e nitrofurantoína aumentou significativamente (p≤0,05) ao longo do período. Não foi detectada resistência a amicacina e carbapenemas. Duas amostras foram produtoras de b-lactamases de espectro ampliado (ESBL). As variáveis independentemente associadas à resistência a ciprofloxacino entre as amostras de E. coli foram: presença de nefrostomia (OR: 4,83; IC95%: 1,15-20,23; p: 0,031), internação (OR: 4,00; IC95%: 1,35-11,85; p: 0,012) e uso de fluoroquinolona (OR: 3,02; IC95%: 1,28-7,91; p: 0,015) nos 3 meses anteriores ao episódio de ITU. Conclusão. A resistência ao ciprofloxacino foi elevada. Os fatores de risco para esta resistência foram aqueles relacionados à manipulação de vias urinárias, sugerindo a possibilidade de transmissão cruzada de amostras resistentes a ciprofloxacino, e o uso prévio de fluoroquinolonas / Objective. To describe the prevalence of resistance to ciprofloxacin and analyze variables potentially associated with this resistance in samples of Escherichia coli isolated from patients with gynecological cancer and urinary tract infection (UTI). Methods. A case-series was conducted between March 2009 and February 2010 at the Cancer Hospital II part of the National Cancer Institute (INCA/HCII) with patients aged over 18 years with gynecological cancer presenting UTI caused by E. coli. Cases were detected through microbiological surveillance in the laboratory of clinical bacteriology in INCA/HCII. Microbiological analyses were performed as recommended by Clinical and Laboratory Standards Institute (CLSI). Clinical and epidemiological data were collected through charts review. For the evaluation of variables potentially associated with resistance to ciprofloxacin the multivariate analysis were performed by logistic regression. Results. Among 275 cases of UTI caused by E. coli in patients with gynecological cancer included in the study, the prevalence of samples resistant to ciprofloxacin was 31%. The prevalence of samples resistant to other antimicrobials such as cefazolin, ceftazidima, fosfomycin, gentamicin and nitrofurantoína increased significantly (p≤0,05) during the period. It was not detected resistance to amikacin and carbapenems. Two samples were producers of extended spectrum b-lactamase (ESBL). The variables independently associated with resistance to ciprofloxacin between samples of E. coli were: undergone nephrostomy (OR: 4.83; IC95%: 1.15-20.23; p: 0.031), hospitalization (OR: 4.00; IC95%: 1.35-11.85; p: 0.012) and use of fluoroquinolone (OR: 3.02; IC95%: 1.28- 7.91; p: 0.015) in the 3 months preceding the episode of UTI. Conclusion. Resistance to ciprofloxacin was high. Risk factors for this resistance were those related to urinary tract manipulation suggesting the possibility of cross transmission of samples resistant to ciprofloxacin, and previous use of fluoroquinolones

Abstract The aims of the work were to evaluate the comparability and repeatability of urodynamic studies and to examine whether such examinations are useful for predicting the recurrence of urinary tract infections or the presence of vesicoureteral reflux, to analyse the efficacy of treatments for vesicoureteral reflux (VUR), to validate a pre-established clinical decision rule for targeting voiding cystourethrograms efficiently in children and to investigate the occurrence of vesicoureteral reflux. Reports on urodynamic examinations performed on children were evaluated by analysing inter-observer and intra-observer agreement in their interpretations, and 116 children were followed up to examine whether such examinations can be used to predict the recurrence of urinary tract infections and the presence of vesicoureteral reflux. A meta-analysis of publications on treatments for vesicoureteral reflux was made to analyse their efficacy in children. A group of 406 children were examined to validate a pre-established clinical decision rule for managing vesicoureteral reflux in children after the first urinary tract infection and to investigate the occurrence of VUR in children. We found poor agreement among the observers in their urodynamic assessments. Neither the occurrence of VUR nor recurrent urinary tract infection could be predicted from the findings in urodynamic studies. The meta-analysis indicated no significant difference between conservative or operative treatment in terms of the recurrence of urinary tract infections, kidney growth or scarring. Our validation of the clinical decision rule showed that it had good specificity but very modest sensitivity in identifying children with dilating vesicoureteral reflux. The overall prevalence of vesicoureteral reflux was 35%, and its occurrence was similar in children without urinary tract infection. We claim that the occurrence of vesicoureteral reflux in children is higher than the figure of 1% suggested earlier. We could not predict the presence or absence of vesicoureteral reflux from the results of the urodynamic examinations, nor could we predict recurrent urinary tract infections from these findings. We suggest that it is not possible to predict VUR reliably, and that conservative treatment is sufficient for the majority of children with VUR. / Tiivistelmä Väitöskirjani tutkimussarjassa selvitimme lapsen virtsateissä tapahtuvan virtsan takaisinvirtauksen (vesikoureteraalinen refluksi, VUR) yleisyyttä ja yhteyttä lasten virtsatieinfektioihin, arvioimme aiemmin julkaistun tutkimusohjeen käyttökelpoisuutta lasten virtsateiden kuvantamispäätöstä tehtäessä ja teimme meta-analyysin virtsan takaisinvirtauksen hoitotapojen merkityksestä munuaisten kehitykselle ja toiminnalle. Selvitimme myös virtsarakon toiminnallisten tutkimusten arviointien toistettavuutta ja vertailtavuutta lastenkirurgien kesken sekä onko näillä tutkimuksilla mahdollista havaita onko lapsella VUR tai taipumusta uusiutuviin virtsatieinfektioihin. Tutkimassamme 406 lapsen aineistossa virtsan takaisinvirtausta löytyi 39&#160;% :lla virtsatieinfektion sairastaneista lapsista ja 36&#160;%:lla muita tulehduksia sairastaneista. Ero ei ollut tilastollisesti merkittävä ja esiintyvyys on huomattavasti suurempi kuin aiemmin on oletettu. Samassa aineistossa testasimme tutkimusohjetta jonka avulla voitaisi löytää lapset joilla on todennäköisesti VUR. Tuloksemme mukaan tutkimusohje ei ole käyttökelpoinen. Kirjallisuuteen perustuvassa meta-analyysissä julkaistuista VUR tutkimuksista lapsilla, havaitsimme, ettei leikkauksella korjattujen tai lääkityksellä hoidettujen lasten munuaisten kasvussa, arpeutumisessa tai virtsatieinfektioiden uusiutumisessa ollut eroa. Virtsarakon toiminnallisten tutkimusten arviointien toistettavuutta lääkärien kesken tutkimme 15 lapsen aineistossa ja havaitsimme huomattavaa vaihtelua arvioinneissa lääkärien välillä ja samaa tutkimusta uudelleen arvioitaessa. Suuren vaihtelun vuoksi näiden tutkimusten hyödyllisyyttä tulisi arvioida kriittisesti. Lisäksi 136 lapsen tutkimuksessa havaitsimme ettei poikkeava virtsarakon toiminnallisen tutkimuksen löydös ennustanut uusiutuvia virtsatieinfektioita tai virtsan takaisinvirtausta näillä lapsilla. Lapsilla VUR on mitä ilmeisimmin varsin tavallinen ilmiö myös terveillä lapsilla ja sen esiintyvyys ylittää aiemmin raportoidun 1&#160;%:n esiintyvyyden. Virtsarakon toiminnalliset tutkimukset eivät ennusta VUR:n esiintyvyyttä tai virtsatietulehdusten toistuvuutta ja näiden tulosten hyöty on vähäinen. Virtsan takaisinvirtauksen leikkaushoitoon on harvoin aihetta eikä arvioimamme tutkimusohje auta löytämään VUR:a sairastavia lapsia.

Orientadores: Carlos Arturo Levi D'Ancona, Edson Antunes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T14:53:15Z (GMT). No. of bitstreams: 1 Oliveira_RicardoRegesMaiade_D.pdf: 1519142 bytes, checksum: f2835a2052000035eb2c8fe2d199ca7b (MD5) Previous issue date: 2009 / Resumo: Sintomas do trato urinário inferior (STUI) estão associados com a piora da Qualidade de Vida dos pacientes e geram custos substanciais para a sociedade. Nos últimos anos houve aumento no conhecimento da fisiopatologia e história natural do STUI e obstrução benigna da próstata (OBP). O óxido nítrico (NO) tem sido implicado como neurotransmissor em vários sítios do sistema nervoso de mamíferos, incluindo as sinapses periféricas do trato urogenital em homens. Estudos recentes avaliaram os efeitos dos inibidores da enzima fosfodiesterase tipo 5 (PDE5) em pacientes com STUI secundário à OBP e observou-se melhora dos sintomas. Como, atualmente, não se sabe o exato papel da sildenafila no tratamento da disfunção miccional associado à OBP foi sugerido em um desses estudos que novas bases fisiopatológicas seriam necessárias para avaliar o efeito do inibidor da fosfodiesterase no trato urinário inferior. Objetivos: Os objetivos deste estudo foram determinar os efeitos urodinâmicos da inibição da síntese de óxido nítrico pela N-nitro-L-arginina metil éster (L-NAME), bem como a ação da sildenafila no trato urinário inferior de ratos com deficiência crônica de NO. Materiais e Métodos: No estudo foram utilizados 27 ratos da espécie Wistar que foram submetidos a estudo urodinâmico, sendo nove controles (Grupo 1), oito tratado com L-NAME (60mk/Kg/dia dissolvido em água) por 30 dias (Grupo 2), quatro tratados somente com sildenafila (100µg/Kg intravenoso) (Grupo 3) e seis tratados com L-NAME por 30 dias seguidos de administração aguda de sildenafila intravenoso(100µg/Kg) (Grupo 4). Resultados: A administração crônica e sistêmica de L-NAME resultou em aumento significativo no número de contrações não associado à micção (0,98 ±0,75 versus 2,71 ±0,89), limiar de volume (1,26 ±0,38 versus 2,8 ±1,64) e frequência dos ciclos de micção (1,2 ±0,65 versus 1,79 ±0,78), comparando Grupos 1 e 2, respectivamente. A administração intravenosa de sildenafila para os animais do Grupo 3 não alterou a frequência (pré-sildenafila 1,23 ±0,37 versus pós-sildenafila 1,3 ±0,15) e a amplitude dos ciclos de micção (pré-sildenafila 8,5 ±3,16 versus pós-sildenafila 9,0 ±2,99). Foi encontrada diferença significativa entre os Grupos 3 e 4 em relação a frequência dos ciclos de micção após administração da sildenafila (1,3 ±0,15 versus 0,35 ±0,25). A amplitude, antes da administração da sildenafila foi maior no Grupo 4 (8,50 ±3,16 versus 27,0 ±8,73; Grupos 3 e 4, respectivamente), porém tornou-se semelhante aos animais do Grupo 3 após a sildenafila (9,0 ±2,99 versus 7,5 ±6,6; Grupos 3 e 4, respectivamente). Conclusões: A redução sistêmica de óxido nítrico promove contrações involuntárias do detrusor e ciclos de micção de menor intervalo. A administração da sildenafila, em animais com deficiência crônica de óxido nítrico, promove diminuição do número de ciclos de micção e da amplitude das contrações. / Abstract: The lower urinary tract symptoms (LUTS) are associated with a worsening in patients' Quality of Life and lead to substantial costs for society. There is a special interest in the development of effective treatment options, with low morbidity, for detrusor overactivity (DO) secondary to benign prostatic obstruction (BPO). Nitric oxide (NO) has been involved as a neurotransmitter in several sites of the nervous system of mammals, including peripheral synapses of the urogenital tract. Sildenafil has been used in the clinical treatment of men with LUTS associated with BPO, with improvement in symptoms. However, this is just one assumption as it has not been proven by experimental studies and the precise role of sildenafil in the treatment of voiding dysfunction associated with BPO is not known. Objective: The aims of this study were evaluate the urodynamic effects of nitric oxide inhibition synthesis by N-nitro-L-arginine methyl ester (L-NAME), as well the action of sildenafil in the lower urinary tract of rats with chronic deficiency of nitric oxide.Materials and Methods: Twenty-seven adult Wistar rats underwent anesthetized cystometrograms: nine controls (Group 1), eight treated with oral L-NAME (60mg/kg/day dissolved in drinking water) for 30 days (Group 2), four treated with sildenafil only (100µg/kg intravenously, IV) (Group 3) and six treated with oral L-NAME for 30 days followed by acute IV sildenafil (100µg/Kg ) (Group 4). Results: The chronic and systemic administration of L-NAME resulted in a significant increase in non voiding contractions (0,98 ±0,75 versus 2,71 ±0,89), volume threshold (1,26 ±0,38 versus 2,8 ±1,64) and frequency of micturition cycles (1,2 ±0,65 versus 1,79 ±0,78), comparing Groups 1 e 2, respectively. The others parameters were not differences. The intravenous administration of sildenafil to Group 3 animals did not significantly alter the frequency (pre-sildenafil 1,23 ±0,37 versus post-sildenafil 1,3 ±0,15) or amplitude of micturition cycles (pre-sildenafil 8,5 ±3,16 versus post-sildenafila 9,0 ±2,99). A significant difference was found between the groups in relation to: void cycles after administration of sildenafil (1,3 ±0,15 versus 0,35 ±0,25). The amplitude before administration was large in Group 4 (8,50 ±3,16 versus 27,0 ±8,73; Groups 3 e 4, respectively), however become similar to that of the Group 3 animals after sildenafil (9,0 ±2,99 versus 7,5 ±6,6; Groups 3 e 4, respectively). Conclusion: The systemic reduction of nitric oxide increase non voiding contractions and frequency of micturition cycles. The administration of sildenafil in animals with chronic deficiency of nitric oxide decreases the number of micturition cycles as well as the contractions amplitude. / Doutorado / Cirurgia / Doutor em Cirurgia

Urinary tract infections (UTI) are among the most common infections in humans. Uropathogenic Escherichia coli (UPEC), the main causative agent of UTIs, can invade and replicate within bladder epithelial cells, and recent evidence demonstrated that some UPEC strains also survive within macrophages. To understand the mechanisms of host subversion that enable UPEC to survive within macrophages, and the contribution of macrophages to UPEC-mediated pathology, I performed host-pathogen co-transcriptome analyses using RNA sequencing. I developed an effective computational framework that simultaneously separated, annotated, and quantified the mammalian and bacterial transcriptomes. First, mouse bone morrow-derived macrophages (BMM) were challenged over a 24 h time course with UPEC reference strains, UTI89 (cystitis strain), 83972 and VR50 (asymptomatic bacteriuria strains) that possess contrasting intramacrophage phenotypes. My results showed that BMM responded to the three different UPEC strains with broadly similar gene expression programs. In contrast to the conserved pattern of BMM responses, the transcriptional responses of the different UPEC strains diverged markedly from each other. Hypothesizing that genes upregulated at 24 h post-infection may contribute to intramacrophage survival, I identified UTI89 genes upregulated at this time point, and showed that deletion of one of these genes (pspA) compromised intramacrophage survival of UPEC strain UTI89. Second, human monocyte-derived macrophages (HMDM) and BMM were challenged over a 24 h course with the UPEC strain EC958, a globally disseminated, multi-drug resistant strain. My analysis identified extensive divergence in UPEC-regulated orthologous gene expression between HMDM and BMM, and I validated both known and novel genes in the context of differential regulation. On the contrary, the transcriptional response of EC958 showed a broad conservation across both mammalian intramacrophage environments. My study thus provides both a unique co-culture approach to study infection in vitro and a technological framework for simultaneously capturing global changes in host-pathogen interactions at the transcriptional level in co-cultures. In conclusion, this work has generated new insights into the mechanisms that UPEC strains exploit to persist within the mouse intramacrophage environment, as well as differences in the transcriptional repertoire of HMDM and BMM challenged with the same UPEC strain.

Introduction: Macroscopic hematuria is an important alarm symptom of cancer in theurinary tract. One single episode in patients over the age of 50 fulfills the criteria for referralto the standardized care pathway. Several patients included in the pathway with a negativeresult of the investigation will return with recurrent macroscopic hematuria for repeatinvestigation. Aim: To evaluate the diagnostic yield of repeat investigation in patients presenting withrecurrent macroscopic hematuria after a previous negative investigation and to estimate theincidence of false negative investigations in the standardized care pathway for cancer in theurinary tract. Material and Methods: A retrospective review of medical records was performed at theDepartment of Urology in Örebro County, including all patients investigated in thestandardized care pathway for cancer in the urinary tract during 2016 with a negative result ofthe investigation. Individuals with repeat investigation were identified. Results of theseinvestigations and the time interval between investigations were documented. Results: Repeat investigation was performed in 96 out of 627 patients (15.3%). Two (2.1%)were diagnosed with cancer, at a time interval from initial investigation of 4 and 27 months,respectively. Other results were benign urological conditions (n = 62) and normalinvestigations (n = 30). Conclusions: It appears that few tumors are missed when macroscopic hematuria isinvestigated in the standardized care pathway. We observed a very low number of newlydiagnosed cancers after repeat investigation of recurrent macroscopic hematuria. A moreselective approach regarding repeat investigations should be considered.

Biofilm is an increasing problem in the healthcare and have in urinary catheters long been associated with nosocomial urinary tract infections. The infections caused in 2002 alone 13,000 deaths in the US and annual costs have been estimated to over $400 million. These costs are however most likely underestimated. The analysis of biofilm is important to aid the work on increasing patient safety and reducing the financial implications. A literature study was conducted in order to recommend a method for quantification that was fast, accurate and versatile. Methods used for biofilm quantification are primarily based upon light absorption, light scattering and changes in impedance. A few methods utilizing these properties are spectrophotometry, flow cytometry and coulter counters. Samples of biofilm are usually collected via traditional scraping with a sterile blade or with sonication (ultrasound). Flow cytometry was considered the superior method for quantification along with sonication for sample collection. The survey therefore came to the conclusion that biofilm sample collection should be done with sonication and analysis with flow cytometry. / Biofilm är ett ökande problem inom sjukvården och har i urinkatetrar länge varit associerademed sjukvårdsrelaterade urinvägsinfektioner. Infektionerna orsakade under 200213,000 dödsfall i USA och de ekonomiska kostnaderna har uppskattats till över $400miljoner. Kostnaderna antas dock vara underskattade. Analysen av biofilm är viktig förarbetet med att förbättra patientsäkerhet och minska kostnader relaterade till biofilm.En litteraturstudie användes för att rekommendera en metod som var snabb, noggrannoch mångsidig. Mätmetoder som används för kvantifiering är i huvudsak baserade påljusabsorption, ljusspridning samt förändringar i elektrisk impedans. Några metodersom använder detta är t.ex. spektrofotometri, flödescytometri samt coulter counters.Prover av biofilm samlas ofta in via traditionell skrapning med ett sterilt knivblad ellermed hjälp av ultraljud. Flödescytometri ansågs vara den bästa metoden för kvantifieringtillsammans med ultraljud för provtagning. Utifrån undersökningen drogs slutsatsen attprovtagning bör ske med ultraljud och analys med flödescytometri.