Orientador: Luis Cuadrado Martin / Coorientador: Vanessa dos Santos Silva / Banca: Adriana Polachino do Vale / Banca: Maria Almerinda Vieira Fernandes / Resumo: Há discordância na literatura quanto à necessidade da realização da microscopia de fase para avaliação da origem da hematúria (glomerular ou não glomerular), isso mostra a necessidade de mais estudos para validar as modalidades de avaliação morfológica da hematúria. Os objetivos deste trabalho foram determinar o melhor ponto de corte da porcentagem dos diferentes padrões de células dismórficas na detecção da hematúria glomerular pelo microscópio óptico convencional e contraste de fase, verificar se a presença de proteinúria ou albuminúria pode auxiliar no diagnóstico da origem da hematúria e determinar o melhor ponto de corte para este parâmetro. Foram avaliadas de maneira cega 131 amostras de urina sendo 66 amostras de portadores de glomerulopatias e 65 amostras dos portadores de litíase renal da Faculdade de Medicina de Botucatu. Utilizaram-se amostras isoladas com densidade >1007 e com mais de 5 hemácias por campo de grande aumento. Verificou-se a presença e a porcentagem de codócitos e acantócitos tanto em microscópio óptico convencional com sedimento fresco e fixado submetidos à coloração de Papanicolaou e Panótico rápido LB e sedimento urinário fresco avaliado em microscópio de contraste de fase, além de determinar o índice de proteinúria e o índice de albuminúria. Os resultados desses métodos foram comparados entre si. Realizou-se regressão linear e diagrama de Bland-Altman das hemácias dismórficas para comparar os diferentes métodos. Curvas ROC foram traçadas para determinar a área sob a curva (ASC) e o melhor ponto de corte (PC) foi determinado pela maior soma de sensibilidade e especificidade. Nesse ponto foram calculadas a sensibilidade (S) e especificidade (Es), Valor Preditivo Positivo (VPP) e Valor Preditivo Negativo (VPN). No microscópio óptico convencional com sedimento urinário fresco, a ASC do dismorfismo eritrocitário total foi a que apresentou ... / Abstract: There is disagreement over the literature regarding the performance of phase microscopy to assess the origin f hematuria (glomerular or nonglomerular). This shows the need for further investigation in order to validate the best form of morphological evaluation of hematuria. The aims of this study were to determine the optimal cutoff point percentage for different patterns of dysmorphic cells in the detection of glomerular hematuria by conventional optical microscopy and phase contrast microscopy, to verify whether the presence of proteinuria or albuminuria may assist in the diagnosis of hematuria and also to establish an optimal cutoff point for this parameter. One hundred thirty-one urine samples were blinded evaluated at the Faculdade de Medicina de Botucatu, 66 samples of patients with glomerulopathies and 65 samples of patients with nephrolithiasis. Isolated samples with density greater than 1007 and with more than 5 erythrocytes per high-power field were used. The presence and percentage of codocytes and acanthocytes were verified by conventional optical microscopy using fresh and fixed urinary sediment subjected to Papanicolaou and Panótico Rápido LB staining and fresh urinary sediment was evaluated by phase contrast microscopy. Proteinuria and albuminuria rates were determined. The results of these methods were compared using linear regression analysis and Bland-Altman diagram of dysmorphic red blood cells. ROC curve plots were generated to determine the area under the ROC curve (AUC) and also an optimal cutoff point with the highest sum of sensitivity and specificity. At this point, it was possible to calculate sensitivity (TPR) and specificity (ES), positive predictive value (PPV) and negative predictive value (NPV). In conventional optical microscope with fresh urinary sediment, the AUC of total dysmorphic erythrocytes showed the best result for the diagnosis of hematuria with AUC (IC 95%) ... / Mestre

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Spontaneous cases of chronic poisoning by Pteridium aquilinum in cattle were studied. The clinical forms of the disease were squamous cell carcinoma (SCCs) of the upper digestive tract (UDT) and bovine enzootic hematuria (BEH). The cases were from the midland Region of the Midwest of Rio Grande do Sul State, Brazil. For the epidemiological study, the profile of the farms was analyzed about herd purpose, main activity of the farm, altitude, and area of plant infestation. No differences were observed among the clinical forms, according to these criteria. Analysis of the ager, gender, and breed of the affected cattle revealed that, in both clinical forms of disease, mixed breed cows (more common in that region) were more affected. In BEH, adult cattle (3-to-7-years-old) were more frequently affected. In the form of UDT SCCs, aged cattle (more than 8- years-old) were more affected. For the clinical study, clinical signs and blood work were evaluated at terminal phase of disease. Cattle with UDT SCCs, had progressive weigth loss, ruminal atony, cough, dysphagia, bloating, and regurgitation. Hematuria was clinically observed in one case of this disease form. In cattle with BEH, hematuria was observed in all cases, followed by progresive weigth loss. Non-regenerative anemia was detected in 33.33% in UDT SCCs form and in 66.66% of BEH form. Changes in white blood count occurred in some cases but drop in lymphocytes was uncommon in both forms of disease. For the morfological study, urinary bladders of 46 UDT SCCs cases and 11 BEH cases were analyzed. Grossly, 16/46 bladders of the UDT SCCs form had gross lesions (vesical red or pale nodules, hemorrhages, and papilomas; red urine in the three cases). In BEH form, the bladder had nodules, large neoplastic masses, red urine, papilomas, and hemorrhages. Pielonephritis and hidronephosis were seen in a few cases. Microscopically, in the UDT SCCs form, 44/46 (95.65%) bladders had 22 different types of morphological changes, caracterized by neoplastic lesions (5/22) and non-neoplastic lesions (17/22), which were subdivided in non-neoplastic epithelial changes (6/17), general changes of the lamina propria (6/17), and inflammatory changes (5/17). The bladder changes in BEH form were of 19 different types, caracterized by neoplastic lesions (5/19) and non-neoplastic lesions (14/19), which were subdivided in non-neoplastic epitelial changes (9/14), general changes of the lamina propria (3/14), and inflammatory changes (2/14). In BEH, mesenchymal neoplasms were more observed than epithelial ones, and most of them were malignant. Immunohistochemistry was utilized to characterize the histogenesis of poorly differentiated neoplasms. In conclusion, the morfological study showed that urinary bladder lesions are very often in cattle with the UDT SCCs form, and were identical to the ones seen in cattle with BEH. / Foram estudados casos espontâneos de intoxicação crônica por samambaia em bovinos nas formas clinicopatológicas de carcinoma de células escamosas (CCE) no trato alimentar superior (TAS) e de hematúria enzoótica bovina (HEB), provenientes da Mesorregião Centro Ocidental do Rio-Grandense e encaminhados ao Laboratório de Patologia Veterinária (LPV) da Universidade Federal de Santa Maria (UFSM). Para o estudo epidemiológico, foi avaliado o perfil das propriedades quanto à finalidade da criação, principal atividade da propriedade, altitude e área de infestação pela planta. Quanto a esses parâmetros, as propriedades com uma ou outra forma de intoxicação crônica não apresentaram diferenças. Foi determinado o perfil dos bovinos afetados quanto à idade, sexo e raça. Os mais afetados por ambas as formas clínicas foram fêmeas de raça mista (predominante na região). Na HEB houve predomínio de bovinos adultos (três a sete anos) e a forma de CCEs no TAS afetou mais bovinos idosos (mais de oito anos). Para o estudo clínico foram avaliados os sinais clínicos de bovinos com CCEs no TAS e com HEB e realizados hemogramas na fase terminal da doença. Os principais sinais clínicos nos bovinos com CCEs no TAS foram emagrecimento progressivo, atonia ruminal, tosse, disfagia, timpanismo, regurgitação e hematúria, vista em um caso. Nos bovinos com HEB, hematúria foi o principal sinal, observado em todos os casos, seguido de emagrecimento progressivo. No exame hematológico, 33,33% dos bovinos com CCEs no TAS e 66,67% dos bovinos com HEB apresentaram anemia arregenerativa. Alterações no leucograma ocorreram em alguns casos, mas linfopenia foi um achado infreqüente em ambas as formas de intoxicação. Para o estudo morfológico, foram avaliadas as bexigas de 46 casos de CCEs no TAS e de 11 casos de HEB. Macroscopicamente, 16/46 bexigas dos casos de CCEs no TAS apresentaram alterações macroscópicas, que foram nódulos vermelhos ou pálidos, hemorragia e papilomas; urina vermelha foi observada em três casos. Nos casos de HEB, os achados macroscópicos vesicais foram nódulos vermelhos, massas neoplásicas focalmente extensas, urina vermelha, papilomas, hemorragias e ruptura de bexiga; pielonefrite e hidronefrose foram observados em poucos casos. Histologicamente, 44/46 (95,65%) bexigas de bovinos com CCEs no TAS apresentaram 22 tipos diferentes de alterações morfológicas, que foram classificadas em alterações neoplásicas (5/22) e alterações não-neoplásicas (17/22), as quais foram divididas em alterações epiteliais não-neoplásicas (6/17), alterações gerais na lâmina própria (6/22) e alterações inflamatórias (5/17). Os achados histológicos das bexigas dos casos de HEB foram classificados da mesma forma, resultando em 19 tipos diferentes de alterações morfológicas. Dessas, 5/19 eram alterações neoplásicas e 14/19, alterações não-neoplásicas (9/14 alterações epiteliais não neoplásicas, 3/14 alterações gerais na lâmina própria e 2/14 alterações inflamatórias). Na HEB, os neoplasmas mesenquimais foram mais observados que os epiteliais, e a maior parte era maligno. A técnica de imuno-histoquímica foi utilizada para caracterizar os aspectos morfológicos, principalmente dos neoplasmas. Através do estudo morfológico concluiu-se que é muito freqüente a ocorrência de lesões vesicais em bovinos com a forma crônica de CCEs no TAS e que essas são idênticas às encontradas nos bovinos com HEB.

La maladie de Berger est la glomérulonéphrite la plus fréquente avec une estimation selon laquelle 1% de la population mondiale serait touchée. L’agent causal est une immunoglobuline (Ig)A anormale (polymérique et hypogalactosylée) qui se dépose dans le mésangium et provoque un dysfonctionnement rénal (protéinurie, hématurie) et des lésions glomérulaires. Dans 25% des cas, la maladie évolue sur 20 ans vers l’insuffisance rénale terminale. Des évidences, de plus en plus nombreuses, montrent que l’environnement microbien, en particulier bactérien, commensal ou pathogène, a un impact important sur le développement de la maladie. Au cours de ma thèse, j’ai d’abord étudié l’effet d’une molécule de la paroi bactérienne, le lipopolysaccharide (LPS), sur la production des IgA dans les muqueuses chez la souris normale. Les résultats que j’ai obtenus et ceux publiés permettent de proposer que la stimulation chronique des muqueuses par l’environnement microbien conduit à une augmentation de la production d’IgA néphrotoxiques, qui, du fait d’un déficit de leur récepteur pIgR mucosal, sont anormalement dirigées vers la circulation plûtôt que dans la lumière es muqueuses. Dans une seconde partie de mon travail, j’ai étudié l’effet du LPS sur le développement de la maladie de Berger dans un modèle de souris 1KI. Ces souris génétiquement modifiées produisent de l’IgA humaine et développent spontanément des dépôts mésangiaux d’IgA mais n’ont pas de protéinurie, d’hématurie ou de lésions glomérulaires. Nos résultats montrent que le LPS provoque une forte hématurie dans les souris 1KI lorsque celles-ci expriment le récepteur des IgA humaines, CD89, à la surface des polymorphonucléaires neutrophiles. En conclusion, mon travail de thèse a permis de mettre en lumière un impact de l’environnement microbien sur pIgR et sur les polymorphonucléaires neutrophiles dont la déficience ou l’activation pourrait contribuer au développement de la maladie de Berger. / IgA nephropathy is the most frequent glomerulonephritis worldwide. It features mesangial immunoglobulin (Ig)A deposits and proteinuria, hematuria and glomerular histological lesions. In 25% patients, it evolves, within 20 years, towards the end stage renal disease. Microbial environment, through the interaction with mucosa, is believed to play a crucial role in the development of the disease. The objectives of my work were to evaluate the effect of the microbial compound lipopolysaccharide (LPS) on the production of the nephritogenic IgA in the mucosa of mice and on the development of IgA nephropathy in the murine model 1KI that spontaneously develops mesangial IgA deposits without the other signs of the disease. Our results and those previously published suggest that the chronic stimulation of mucosa by microbiota leads to the increased production of nephritogenic IgA in the mucosa. These IgA, thanks to a deficient mucosal receptor pIgR in patients with IgA nephropathy, may be abnormally routed in the blood. We also showed that LPS provokes hematuria in the 1KI mice, when they express a specific IgA receptor, CD89, on the surface of polymorphonuclear neutrophils. Altogether our findings highlight the impact of microbial environment on pIgR and on polymorphonuclear neutrophils and thus, potentially, on IgA nephropathy.

Computed tomography urography (CTU) is today the imaging method used to investigate patients with suspected urinary tract malignancy, replacing the old imaging method intravenous pyelography (IVP) about a decade ago. The downside of this shift was that the effective radiation dose to the examined patient was eight times higher for CTU compared to IVP. Based on four different studies, the present thesis focused on efforts to reduce the CTU radiation dose.   In study I, the number of cysts and solid lesions in the separate scan phases was evaluated in 57 patients undergoing four-phase CTU 1997-98. The number of scans was reduced from four to three when the nephrographic scan was abolished following study I. Study II registered the diameter of renal cell carcinoma (RCC) and the presenting symptoms in the total number of patients (n=232) diagnosed with RCC between 1997 and 2003. The results from study II showed that the critical size for RCCs to cause macroscopic hematuria was ≥ 4 cm. Study III was a dose-escalation study aimed to decide the minimal possible tube load in the unenhanced and excretory phase scans if the low dose images are reviewed together with normal dose corticomedullary phase images. Study III showed that it is possible to reduce the mean effective dose in three phase CTU from 16.2 mSv to 9.4 mSv with a combined low and normal dose CTU protocol. Study IV investigated the changes in the CTU protocol between 1997 and 2008, and the development of the effective radiation dose. Study IV clarified how the CTU protocol has changed between 1997 and 2008 and as a result the mean effective radiation dose to patients undergoing CTU in 2008 is only 39% of the effective dose in 1997.   In conclusion, the findings from the studies included in this thesis have contributed to a reduced radiation dose to patients undergoing CTU. The mean effective dose from CTU is at present only three times higher compared to that from the IVP.

Made available in DSpace on 2016-04-28T20:18:35Z (GMT). No. of bitstreams: 1 LUIS GUSTAVO PICORELLI DE OLIVEIRA 1-75.pdf: 8291753 bytes, checksum: d0e3e8919d70356d42c7098b6af1d1a4 (MD5) Previous issue date: 2009-01-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Ninety bovine bladders, from a slaughterhouse from the district of Barra Mansa/RJ and from bovine necropsies in Pteridium arachnoideum invaded locations, were examined when associated with clinical signs as those found in bovine enzootic hematuria. A diffuse wrinkling of the bladder mucosa was found in 40% of the cases which was correlated to increased mucous normal irregularity, polyp proliferation, lamina propria thickening, fibrose and, in severe cases, urotelial carcinoma multicentric proliferation of endophitic growth. Papillary tumours were microscopically classified as urotelial carcinoma in 35% of cases and papiloma in 65%. In some cases, carcinoma and adenocarcinoma presented less commom differentiation patterns as intestinal, of Paneth cells, and a mesonefroid adenocarcinoma in the trigone area, which demonstrated bladder embryological origin influence on different types of lesions that were found. Mucosal hemorrhagic lesions occurred in 100% of the cases and were associated with vascular proliferation and lamina propria hemorrhage or, in sever cases, 77,4% of hemorrhagic elevations were correlated to hemangioma or hemangiosarcoma. At last, we have established a correlation between P. arachnoideum chronic poisoning lesions and ionizing radiation bladder alteration in humans. / Em um frigor?fico no munic?pio de Barra Mansa, RJ, e por ocasi?o de visitas a campo em regi?es infestadas pela Pteridium arachnoideum, foram coletadas 90 bexigas de bovinos que apresentavam sinais cl?nicos e ou les?es macrosc?picas compat?veis com o quadro de hemat?ria enzo?tica. As les?es encontradas tanto ao exame macrosc?pico quanto microsc?pico foram mais frequentes no corpo e na base da bexiga. ? macroscopia um enrugamento difuso da mucosa da bexiga foi observado em 40% dos casos, o que foi correlacionado ao aumento do pregueamento da mucosa, ? prolifera??o de p?lipos, ao espessamento da l?mina pr?pria, ? fibrose e, nos casos mais graves, ? prolifera??o multic?ntrica de carcinomas uroteliais com crescimento endof?tico. Tumores papiliformes foram classificados microscopicamente como carcinomas uroteliais em 35% dos casos e papilomas em 65%. Carcinomas e adenocarcinomas apresentaram, em alguns casos, diferencia??es consideradas pouco frequentes, como intestinal, em c?lulas de Paneth e em c?lulas claras. Um adenocarcinoma mesonefr?ide foi encontrado na posi??o do tr?gono, o que demonstra a influ?ncia da origem embriol?gica da bexiga sobre os tipos de les?es encontradas. Les?es hemorr?gicas na mucosa ocorreram em 100% dos casos, e estavam correlacionados a prolifera??es vasculares e hemorragias na l?mina pr?pria ou, nos casos mais graves, 77,4% das eleva??es hemorr?gicas foram correlacionadas a hemangiomas ou a hemangiossarcomas. Foi estabelecida uma identidade entre as les?es produzidas pela intoxica??o cr?nica por P. arachnoideum em bovinos e as altera??es provocadas na bexiga de seres humanos expostos a radioterapia ou ? radia??o ionizante ambiental.

<p> Inherited bleeding disorders can be caused by mutations affecting platelet, coagulation, or fibrinolytic proteins. Quebec platelet disorder (QPD) is a rare, autosomal dominant disorder associated with increased expression of the fibrinolytic enzyme urokinase plasminogen activator (uPA) in platelets. Individuals with QPD experience delayed-onset bleeding after hemostatic challenges that is attenuated with fibrinolytic inhibitor therapy. The aims of this thesis were to: 1) determine if increased platelet uPA contributes to QPD clot lysis in vitro; 2) investigate whether QPD individuals have increased urinary uPA, as some individuals experience hematuria; and 3) map the genetic locus of QPD, and look for the putative mutation. Studies of clot lysis indicated that QPD platelets induce a gain-of-function defect in fibrinolysis when platelets are incorporated into clots. This suggests that accelerated fibrinolysis may contribute to QPD bleeding. Studies of urinary uPA in QPD showed that uPA is not increased, indicating that hematuria in QPD is likely a consequence of increased platelet uPA. This finding also suggests that uPA overexpression in QPD may be megakaryocyte-specific. Linkage studies showed that QPD is strongly linked to a 2 megabase region on chromosome 10 that harbors the uPA gene, PLA U. No mutations in PLA U or its regulatory regions were identified; however, a common haplotype for a 32.5 kilobase region around PLA U, including inheritance of a rare, linked polymorphism, suggests this is the most likely locus for QPD. mRNA studies in QPD platelets showed that QPD selectively increases expression of the linked PLAU allele, without similar increases in megakaryocyte progenitors or in saliva. These findings implicate a cis-mutation near PLA U as the cause of QPD. This thesis provides novel insights on the fibrinolytic abnormality in QPD blood, and on the QPD genetic locus. which will be important for identifying the precise mutation that converts normally prohemostatic platelets to profibrinolytic cells. </p> / Thesis / Doctor of Philosophy (PhD)

Pacientes submetidos ao transplante de medula óssea, apresentando hematúria/cistite hemorrágica, tiveram amostras de urina analisadas pela microscopia eletrônica. Esta foi a técnica escolhida de pesquisa viral pela sua confiabilidade. Noventa em 402 pacientes submetidos ao transplante de medula óssea neste serviço apresentaram hematúria/cistite hemorrágica (incidência de 22%). O estudo por microscopia eletrônica foi realizado em 72 destes pacientes com hematúria/cistite hemorrágica (grupo de estudo), identificando 55,6% (40/72) de positividade viral. Foram também estudadas amostras de urina de 12 pacientes submetidos ao transplante de medula óssea sem hematúria/cistite hemorrágica (grupo controle); houve associação significante entre a presença de vírus e hematúria/cistite hemorrágica (p<0,01 - Teste exato de Fisher). No grupo com hematúria/cistite hemorrágica, 65% (26/40) dos vírus detectados pertenciam à família Poliomaviridae, 30% (12/40) à Adenoviridae, e 5% (2/40) foram positivos para ambas as famílias. Houve associação entre a positividade para vírus e a presença da doença enxerto-contra-hospedeiro (p=0,05-x2) e o de início tardio (>dia+21) da H/CH (P=0,04-x2), bem como entre a doença enxerto-contra-hospedeiro e a severidade da H/CH (p=0,04-x2). O presente estudo mostra que a microscopia eletrônica é uma ferramenta útil para detecção de vírus na urina de pacientes submetidos ao transplante de medula óssea apresentando hematúria/cistite hemorrágica e que o vírus provavelmente tem um papel no desenvolvimento do sangramento urinário, o qual é agravado pelo doença enxerto-contra-hospedeiro. A microscopia eletrônica deveria ser realizada rotineiramente para guiar as outras técnicas de detecção viral, como a imunocitoquímica e biologia molecular. / Patients submitted to bone marrow transplantation presenting hematuria/hemorrhagic cystitis had the urine analyzed by electron microscopy. It was the elected technique for viral search because its reliability. Ninety from 402 patients submitted to bone marrow transplantation at this service showed hematuria/hemorrhagic cystitis (incidence of 22%). Electron microscopy study was performed in 72 of these patients with hematuria/hemorrhagic cystitis (study group), identifying 55.5% (40/72) of viral positivity. It was also study the urine of 12 patients submitted to bone marrow transplantation without hematuria/hemorrhagic cystitis (control group); there was a significant association between the presence of virus and hematuria/hemorrhagic cystitis (p<0.01). In the hematuria/hemorrhagic cystitis group, 65% (26/40) of the virus belonged to Poliomaviridae family, 30% (12/40) to Adenoviridae, and 5% (2/40) to both families. There was association between the status of graft-versus-host disease and positivity for virus (p=0.05), as well as between graft-versus-host disease and the severity of hematuria/hemorrhagic cystitis (p=0.04). The present study shows that electron microscopy is a useful tool for detection of virus in urine of patients submitted to bone marrow transplantation presenting hematuria/hemorrhagic cystitis and that the virus probably play a role in the development of the urinary bleeding, which is aggravated by graft-versus-host disease. Electron microscopy should be performed routinely to guide the other techniques for viral detection, like immunocitochemistry and molecular biology.

Pacientes submetidos ao transplante de medula óssea, apresentando hematúria/cistite hemorrágica, tiveram amostras de urina analisadas pela microscopia eletrônica. Esta foi a técnica escolhida de pesquisa viral pela sua confiabilidade. Noventa em 402 pacientes submetidos ao transplante de medula óssea neste serviço apresentaram hematúria/cistite hemorrágica (incidência de 22%). O estudo por microscopia eletrônica foi realizado em 72 destes pacientes com hematúria/cistite hemorrágica (grupo de estudo), identificando 55,6% (40/72) de positividade viral. Foram também estudadas amostras de urina de 12 pacientes submetidos ao transplante de medula óssea sem hematúria/cistite hemorrágica (grupo controle); houve associação significante entre a presença de vírus e hematúria/cistite hemorrágica (p<0,01 - Teste exato de Fisher). No grupo com hematúria/cistite hemorrágica, 65% (26/40) dos vírus detectados pertenciam à família Poliomaviridae, 30% (12/40) à Adenoviridae, e 5% (2/40) foram positivos para ambas as famílias. Houve associação entre a positividade para vírus e a presença da doença enxerto-contra-hospedeiro (p=0,05-x2) e o de início tardio (>dia+21) da H/CH (P=0,04-x2), bem como entre a doença enxerto-contra-hospedeiro e a severidade da H/CH (p=0,04-x2). O presente estudo mostra que a microscopia eletrônica é uma ferramenta útil para detecção de vírus na urina de pacientes submetidos ao transplante de medula óssea apresentando hematúria/cistite hemorrágica e que o vírus provavelmente tem um papel no desenvolvimento do sangramento urinário, o qual é agravado pelo doença enxerto-contra-hospedeiro. A microscopia eletrônica deveria ser realizada rotineiramente para guiar as outras técnicas de detecção viral, como a imunocitoquímica e biologia molecular. / Patients submitted to bone marrow transplantation presenting hematuria/hemorrhagic cystitis had the urine analyzed by electron microscopy. It was the elected technique for viral search because its reliability. Ninety from 402 patients submitted to bone marrow transplantation at this service showed hematuria/hemorrhagic cystitis (incidence of 22%). Electron microscopy study was performed in 72 of these patients with hematuria/hemorrhagic cystitis (study group), identifying 55.5% (40/72) of viral positivity. It was also study the urine of 12 patients submitted to bone marrow transplantation without hematuria/hemorrhagic cystitis (control group); there was a significant association between the presence of virus and hematuria/hemorrhagic cystitis (p<0.01). In the hematuria/hemorrhagic cystitis group, 65% (26/40) of the virus belonged to Poliomaviridae family, 30% (12/40) to Adenoviridae, and 5% (2/40) to both families. There was association between the status of graft-versus-host disease and positivity for virus (p=0.05), as well as between graft-versus-host disease and the severity of hematuria/hemorrhagic cystitis (p=0.04). The present study shows that electron microscopy is a useful tool for detection of virus in urine of patients submitted to bone marrow transplantation presenting hematuria/hemorrhagic cystitis and that the virus probably play a role in the development of the urinary bleeding, which is aggravated by graft-versus-host disease. Electron microscopy should be performed routinely to guide the other techniques for viral detection, like immunocitochemistry and molecular biology.

Thesis (Ph. D.)--Uniformed Services University of the Health Sciences, 2005. / Typescript (photocopy).

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