Introdução: Um dos principais obstáculos para compreensão dos eventos biológicos envolvidos no câncer é a falta de modelos adequados para o estudo in vitro em especial em relação ao câncer de próstata (CaP) e ao câncer de bexiga (CaB). Há um número limitado de linhagens celulares de CaP e de CaB sendo a maioria proveniente de tumores invasivos e metastáticos. Sabe-se ainda, que existem diferenças étnicas entre as populações quanto ao comportamento de neoplasias. Desta forma, a pesquisa baseada em linhagens de uma população homogênea seria fonte de resultados limitados, não contemplando a diversidade que sabidamente ocorre entre os diferentes grupos. Além desse aspecto, as linhagens celulares comerciais são na sua maioria adquiridas na Coleção Americana de Culturas de Tecido (ATCC, do inglês American Tissue Cell Culture) que apesar de serem bem padronizadas, requerem processos de importação com aumento do custo e demandas burocráticas que dificultam a pesquisa. Portanto, consideramos vital para a compreensão dos fenômenos relacionados à carcinogênese, assim como estudos de resistência a drogas, quimioprevenção e novas estratégias terapêuticas, o desenvolvimento de linhagens tumorais derivadas de tumores primários que acometem a nossa população, peculiarmente miscigenada. No presente trabalho, fragmentos de carcinoma urotelial da bexiga e de adenocarcinoma da próstata foram obtidos durante cirurgia para remoção de tumores primários de pacientes tratados e acompanhados na Divisão de Urologia da Faculdade de Medicina da Universidade de São Paulo (FMUSP) e no Hospital Sírio Libanês. As linhagens estabelecidas a partir destes fragmentos foram caracterizadas através da análise da cinética de crescimento, análises imunocitoquímicas e anormalidades cromossômicas incluindo cariótipo e hibridização in situ por fluorescência (FISH). Além disso, as linhagens obtidas foram submetidas a estudos de quimiossensibilidade com o uso dos compostos curcumin e Prima-1. Avaliamos ainda, a tumorigenicidade de nossas linhagens em camundongos atímicos. Os resultados deste trabalho demonstram o desenvolvimento de três linhagens de CaB e três linhagens de CaP sendo as mesmas não tumorigênicas em camundongos atímicos. Além disso, demonstramos que o curcumin na concentração de 50 M induziu morte celular em todas as linhagens estudadas, sendo seu efeito mais evidente nas linhagens de CaP. Por fim, Prima-1 reduziu a viabilidade celular independente do status de p53 nas linhagens de CaB / Introduction: One of the main obstacles for understanding biological events involved in cancer is the lack of appropriated models for in vitro studies especially for prostate cancer (PC) and bladder cancer (BC). There are a limited number of PC and BC cell lines being the majority originated from metastatic and invasive tumors. Also it is well known that there are ethnic differences between populations concerning the behavior of tumors. In such a way, the research based on cell lines derived from a homogenous population should be source of limited results, not contemplating the diversity known to occur among different groups. In addition the commercial cell lines are generally acquired at American Tissue Cell Culture (ATCC) that although wellestablished requires importation processes with cost increase and bureaucratic demands that difficult the research. Therefore we consider vital to the comprehension of the carcinogenesis phenomena, as well as drug resistance studies, chemoprevention and new therapeutic strategies, the development of tumor lineages derived from primary tumors that assail our miscigenated population. At the present work, fragments of bladder urothelial carcinoma and prostate adenocarcinoma were obtained by surgical resection of primary tumors from patients treated and followed in the Division of Urology of the Clinical Hospital of the São Paulo University (FMUSP) and Syrian Lebanese Hospital. The cell lines established from these fragments were characterized through growth kinetic, immunocytochemistry and chromosome abnormalities including karyotyping and Fluorescence in situ hybridization (FISH). Moreover, the cell lines were submitted to chemosensitivity studies using curcumin and Prima-1 and analyzed regarding their tumorigenicity in athymic mice. The results of this work show the development of three BC and three PC cell lines that were not tumorigenic in athymic mice. Curcumin at 50 M concentration induced cell death in all studied lineages, being more effective in PC cell lines. Finally, PRIMA-1 reduced the cellular viability independent of the p53 status in BC cell lines

Introdução: Ocupação foi identificada como o segundo fator de risco mais importante para o câncer de bexiga depois de fumar sendo responsável por até 20% de todos os cânceres de bexiga em países industrializados. Apesar dos esforços consideráveis para investigar ocupações em relação ao risco de câncer de bexiga, muitas não foram encontrados de forma consistente. Material e Métodos: Foram incluídos 200 pacientes com diagnóstico de câncer de bexiga entre os anos de 2009 e 2013. Foi aplicado um questionário para obter informações sobre a profissão, tempo de exposição e hábitos diários, sintomas, e também dados de doenças incluindo estágio, grau e número e tamanho de lesões. Os pacientes do Grupo 1 foram aqueles sem emprego previamente associados com o risco de câncer de bexiga. Grupo 2 representado pacientes em risco devido a profissões. Resultados: Os pacientes do Grupo 2 apresentaram uma proporção significativamente maior de pT2 CaB (P = 0,037), enquanto que os pacientes do grupo 1 apresentaram significativamente mais pTa (p = 0,002) da doença. Analisando preditores de pT2, a presença de ocupação aumento de alto risco por 2,80 vezes a chance de desenvolver uma doença invasiva. Ao analisar o grau do tumor descobriram que um tempo de exposição de 10 anos ou mais aumenta o risco de tumores de alto grau em 4,28 vezes (p = 0,001). Conclusão: Pacientes com história de exposição a agentes cancerígenos devido à sua atividade profissional podem estar em maior risco de desenvolvimento de tumores invasivos e aqueles que estão expostos a estes agentes para mais de 10 anos podem desenvolver doença de alto grau com mais freqüência. População em risco pode, portanto, beneficiar de rastreamento para o câncer de bexiga / Occupation was identified as the second most important risk factor for bladder cancer after smoking accounting for up to 20% of all bladder cancers in industrialized countries. Despite considerable efforts to investigate occupation against the risk of bladder cancer, many have not been found consistently. We included 200 patients diagnosed with bladder cancer between 2009 and 2013. A questionnaire was applied to obtain information about the profession, exposure time and daily habits, symptoms, and also diseases of data including stage, grade and number and lesion size. Patients in Group 1 were those without jobs previously associated with the risk of bladder cancer. Group 2 represented patients at risk because of professions. Group 2 patients had a significantly higher proportion of pT2 CaB (P = 0.037), whereas patients in group 1 had significantly more pTa (p = 0.002) of the disease. Analyzing predictors of pT2, the presence of high-risk occupation increases by 2.80 times the chance of developing invasive disease. In considering the degree of tumor found that a time of 10 or more years of exposure increases the risk of high-grade tumors in 4.28 times (p = 0.001). Patients with a history of exposure to carcinogens because of their duties may be at greater risk of developing invasive tumors and those who are exposed to these agents for more than 10 years can develop high-grade disease more often. Population at risk can therefore benefit from screening for bladder cancer

Orientador: Paulo Cesar Rodrigues Palma, Viviane Herrmann / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T10:39:24Z (GMT). No. of bitstreams: 1 Bellette_PatriciaOdila_M.pdf: 1141308 bytes, checksum: 2b1b008fc3d9ef462a5114d38968193e (MD5) Previous issue date: 2007 / Resumo: O objetivo deste estudo foi avaliar a eficácia da eletroestimulação do nervo tibial posterior em mulheres com hipótese diagnóstica de Bexiga Hiperativa e suas repercussões na qualidade de vida. Sujeitos e métodos: para este ensaio clínico prospectivo, controlado e randomizado foram convidadas a participar do estudo 37 mulheres consultadas no ambulatório de uro-ginecologia do Hospital das Clínicas (HC) da UNICAMP, que cumpriram os critérios de inclusão e exclusão. Foram aleatoriamente alocadas em dois grupos. Grupo tratamento: as mulheres foram tratadas com o uso da eletroestimulação transcutânea do nervo tibial posterior (n = 21) e Grupo placebo: as mulheres tiveram os eletrodos alocados, mas sem passagem de corrente elétrica (n = 16). No primeiro contato com a paciente foi feito o convite para participar do estudo e realizada uma avaliação fisioterapêutica, incluindo preenchimento do diário miccional de três dias e dos questionários de qualidade de vida (ICIQ, KHQ e OABq). Na aplicação da técnica utilizou-se oito sessões de eletroestimulação transcutânea do nervo tibial posterior. Resultados: A noctúria apresentou melhora significativa no grupo tratamento (p=0,003) e uma tendência de maior melhora no grupo tratado (p=0,054). A frequência urinária diminuiu significativamente no grupo tratamento (p=0,003) e a urgência miccional diminuiu também em ambos os grupos (placebo:p=0,025 e tratamento:p=0,002). Com relação aos questionários utilizados, apenas o OABq foi responsivo, tanto no escore total (p=0,037), quanto no escore severidade (p=0,018). Conclusão: A eletroestimulação transcutânea do nervo tibial posterior é uma ferramenta eficaz no tratamento fisioterapêutico da Bexiga Hiperativa. / Abstract: The aim of this study was to evaluate the effect of the electrical stimulation of the posterior tibial nerve on the quality of life in women with overactiv bladder syndrome. Subjects and methods: thirty seven women from to Urogynecology Division of the Hospital das Clínicas de Campinas (HC/UNICAMP) were invited to participate in a prospective randomized trial. After screening inclusion and exclusion criteria, they were randomly placed in one of two groups: Treatment group: the women were submitted to tibial posterior nerve electrical stimulation (n = 21) and Sham group: the women had electrodes placed on the tibial posterior nerve, without stimulation (n = 16). At first, the patients were invited to participate in the study and submitted to a physiotherapeutic evaluation, including fulfilling a three days diary, quality of life questionnaires (ICIQ, KHQ an OABq). The approach of the treatment was eigth sessions of electrical stimulation on the posterior tibial nerve. Results: noctury was significantly improved in the treatment group (p=0,003). The urinary frequency was significantly improved in treatment group (p=0,003) and the urgency decreased significantly in both groups (sham:p=0,025 and treatment p=0,002). Comparing the questionnaires applied only the OABq was responsive in both scores, total score (p=0,037) and severity score (p=0,018). Conclusion: The posterior tibial nerve electrical stimulation is an effective physiotherapeutic treatment in overactive bladder. / Mestrado / Mestre em Cirurgia

Orientador: Edson Antunes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T08:00:03Z (GMT). No. of bitstreams: 1 Ramos-Filho_AntonioCelsoSaragossa_D.pdf: 3024613 bytes, checksum: a03a80c65d863acd441249f461461216 (MD5) Previous issue date: 2014 / Resumo: Os receptores TRPV4 e TRPM8 são expressos no urotélio e em fibras aferentes sensitivas da bexiga. Fisiologicamente, a ativação mecânica do receptor TRPV4 na parede da bexiga participa do controle miccional. Em doenças de origem inflamatória, esses receptores adquirem funcionalidade importante. As disfunções da bexiga no diabetes podem estar associadas a alterações ao nível de detrusor, inervação e urotélio. A disfunção urotelial parece ser a responsável por desencadear as alterações neurais e musculares da bexiga. Assim, o objetivo do presente estudo foi investigar os mecanismos fisiopatológicos da ativação dos receptores TRPV4 e TRPM8 no estado diabético em camundongos. Para tanto, dividimos o estudo em duas etapas, sendo que na primeira avaliamos a participação dos receptores TRPV4 e TRPM8 nos mecanismos contráteis e relaxantes do detrusor isolado de animais controles e knockout para esses canais. Em uma segunda etapa estudamos a ativação desses canais em camundongos diabéticos pela injeção intraperitoneal de estreptozotocina (180 mg/Kg) por 4 semanas. Em fragmentos do detrusor isolados de camundongos mostramos que o agonista do receptor TRPV4, GSK1016790A, causou resposta contrátil dependente da concentração. Por outro lado, quando os tecidos foram contraídos com solução despolarizante de KCl, o GSK1016790A causou relaxamento da preparação. No detrusor isolado de animais TRPV4-/- verificamos hipercontratilidade ao carbacol (agonista muscarínico) e à estimulação elétrica, assim como redução no relaxamento ao agonista ?-adrenérgico não-seletivo, isoprenalina. Estes efeitos não foram obtidos com os antagonistas dos receptores TRPV4, RN1734 e HC067047. A indução do diabetes causou nocicepção mecânica e aumento da proporção entre bexiga e peso corpóreo após 4 semanas da injeção. A avaliação miccional dos animais diabéticos mostrou aumento da capacidade, frequência urinária e das contrações involuntárias da bexiga. Observamos ainda hipercontratilidade do detrusor ao carbacol, à estimulação elétrica e ao KCl. A indução do diabetes em animais TRPV4-/- não modificou as disfunções "in vivo" e "in vitro" observadas nos animais wyld type diabéticos, mostrando que a ausência crônica dos receptores TRPV4 desencadeia alterações miccionais que são anteriores as causadas pelo diabetes. Também verificamos que os animais TRPM8-/- não apresentam alteração na resposta contrátil ao carbacol e à estimulação elétrica. Por outro lado, o mentol, mas não a icilina, reduziu significativamente as respostas contráteis nestes animais. O mentol inibiu o influxo de cálcio extracelular em cultura de células da musculatura lisa da bexiga por mecanismo inibitório direto nos canais Cav1.2. O tratamento agudo com mentol, intraperitoneal e intravesical, atenuou as disfunções miccionais observadas nos camundongos diabéticos. "In vitro" o pré-tratamento com mentol reduziu a hipercontratilidade ao carbacol no grupo diabético, sem alterar a resposta no grupo controle. Concluímos que o mentol impede a resposta contrátil da bexiga por mecanismo independente do receptor TRPM8 bloqueando o influxo de cálcio extracelular nos canais Cav1,2, podendo ser utilizado como tratamento na hiperatividade de bexiga de origem miogênica / Abstract: The TRPV4 and TRPM8 receptors are expressed in bladder urothelium and sensitive afferent fibers. Physiologically, the mechanical activation of TRPV4 receptor in the bladder wall is involved in micturition control. In inflammatory diseases, these receptors may have important roles. The bladder dysfunction in diabetes may be associated with changes at the level of detrusor, innervation and urothelium. The urothelial dysfunction triggers neural changes, modifying consequently the smooth muscle contractility. Thus, the goal of the present study was to investigate the pathophysiological mechanisms of TRPV4 and TRPM8 receptor activation in physiological and diabetic conditions in mice. For this purpose we divided the study in two phases, the first of which we evaluated the participation of TRPV4 and TRPM8 receptors in detrusor contractile and relaxing mechanisms in control and knockout animals for these channels. In the second phase we studied the activation of these channels in diabetic mice induced by intraperitoneal injection of streptozotocin (STZ; 180 mg / kg, 4 weeks). The TRPV4 agonist GSK1016790A produced concentration-dependent detrusor contractions. On the other hand, in detrusor pré-contracted with KCl (80 mM), GSK1016790A caused relaxation responses. In TRPV4-/- animals, we verified hypercontractility to carbachol (muscarinic agonist) and electrical-field stimulation, as well as a decreased relaxation to isoprenaline (non-selective ?-adrenergic agonist). These effects were not obtained with the TRPV4 antagonists, RN1734 and HC067047. Induction of diabetes with STZ caused hyperglycemia, mechanical nocicepton, and increased ratio between bladder and body weight after 4 weeks. The miccturition evaluationin diabetic animals showed increased capacity, urinary frequency, and non-voiding contractions. Hypercontractility to carbachol, electrical-field stimulation and KCl in isolated detrusor were lso observed. The induction of diabetes in TRPV4-/- animals did not change the urinary dysfunctions. Our data are consistent with the proposal that TRPV4 receptor has a physiological function in micturition control by decreasing muscarinic-induced contractions and increasing ?-adrenergic-mediated relaxations. Moreover, the bladder contractions to carbachol and EFS in TRPM8-/- did not significantly change compared to TRPM8+/+. However, menthol (300 ?M), but not icilin (1 ?M), significantly inhibited these contractile responses. The menthol (300 ?M) inhibited extracellular calcium influx in bladder smooth muscle cell culture by direct mechanism though Cav1.2 channels. In addition the acute treatment with menthol, intraperitoneal and intravesical, atenuated the micturition dysfunctions observed in diabetic mice. Also, detrusor preparations pre-treated with menthol decreased carbachol hypercontractility, without changing the responses in normoglycemic group. Menthol reduces bladder contractions by mechanisms independent of TRPM8 receptor activation, inhibiting extracellular calcium influx through Cav1.2 channel, thus been considered as treatment for bladder overactivity of myogenic origin / Doutorado / Farmacologia / Doutor em Farmacologia

Orientador: Cássio Luis Zanettini Riccetto / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T12:04:58Z (GMT). No. of bitstreams: 1 Palma_ThaisFigueiredo_D.pdf: 5188121 bytes, checksum: 3443d8a70ab4644713a51d88beb4d20c (MD5) Previous issue date: 2014 / Resumo: Introdução: A Síndrome da Bexiga Hiperativa (BH) é definida pela ICS (International Continence Society) como urgência urinária, acompanhada ou não por incontinência e frequentemente associada ao aumento da frequência urinária e noctúria. Objetivo: O objetivo do estudo foi verificar a influência da idade, do índice de massa corporal (IMC) e de antecedentes gestacionais nos sintomas de bexiga hiperativa em mulheres no menacme. Pacientes e Métodos: No total foram avaliados os questionários preenchidos por 1052 mulheres com idade entre 20 e 45 anos na região de Campinas. Foi utilizado o questionário ICIQ-OAB, uma ferramenta específica para bexiga hiperativa, em sua versão validada em Português e uma ficha de avaliação para dados demográficos e história médica, incluindo: idade, peso, altura, paridade e via de parto. Resultados: De modo geral, mulheres com idade entre 35 e 45 anos apresentaram escore do ICIQ-OAB significativamente maior do que todos os outros grupos (20 a 22; 23 a 27 e 38 a 34) (p<0.0001). Mulheres multíparas e primíparas apresentaram escore significativamente maior do que as nulíparas (p<0,001); e os sintomas não diferiram de acordo com a via de parto - vaginal ou cesárea (p=0.0074). Não foram encontradas diferenças significativas no escore entre os grupos de IMC (<18,5; 18,8 a 24,9; 25 a 29,9 e ? 30) (p=0,0066). Também foram encontradas diferenças significativas com relação ao incômodo causado pelos sintomas. Mulheres de 35 a 45 anos se sentem mais incomodadas do que os outros grupos com relação á frequência (p<0.0001), noctúria (p=0.0011), urgência (p=0.0015) e incontinência por urgência (p<0.0001). O incômodo causado pelos sintomas não diferiu entre os grupos de mulheres nulíparas, primíparas e multíparas (p=0,9363). As mulheres com IMC entre 25 e 29,9 apresentaram incômodo maior do que aquelas com IMC entre 18,5 e 24,9, com relação à incontinência por urgência (p=0,002). Conclusões: Na população estudada de mulheres no menacme, os sintomas de bexiga hiperativa são encontrados mais frequentemente e causam mais incômodo em mulheres com idade mais avançada, índice de massa corporal mais elevado e com histórico de pelo menos uma gestação / Abstract: Introduction: Overactive Bladder Syndrome (OAB) is defined by the ICS (International Continence Society) as urinary urgency, with or without urgency incontinence and frequently associated with increase of frequency and nocturia. Objectives: The aim of the study was to verify the influence of age, body mass index (BMI) and obstetric history in the symptoms of overactive bladder in premenopausal women. Patients and Methods: We analyzed a total of 1052 questionnaires that were filled out by women aged 20-45 in the area of Campinas, SP. We chose the ICIQ-OAB questionnaire, a tool that is specific for overactive bladder, in its Portuguese validated version and na assessment form with demographics and medical history, that included: age, weight, height, parity and mode of delivery (vaginal or cesarean). Results: Overall, women aged 35-45 presented higher scores than all other age groups (20 - 22; 23 - 27 and 38 - 34) (p<0.0001). Multiparous and primiparous women presented higher scores than nulliparous ones (p<0,001); and the symptoms did not differ according to mode of delivery ¿ vaginal or cesarean (p=0.0074). No significant differences were found between the BMI groups - <18,5; 18,8 - 24,9; 25 - 29,9 and ? 30 - (p=0,0066). We also found differences regarding symptom bother. Women aged 35-45 were more bothered than all other groups regarding frequency (p<0.0001), nocturia (p=0.0011), urgency (p=0.0015) and urgency incontinence (p<0.0001). Symptom bother did not differ between nuliparous, primiparous and multiparous women (p=0,9363). Women with BMI 25 - 29,9 were more bothered by urgency incontinence than those with BMI 18,5 - 24,9 (p=0,002). Conclusions: In the premenopausal women population of this study, OAB symptoms were found more frequently and cause more bother in older women, with higher BMI and with history of at least one pregnancy / Doutorado / Fisiopatologia Cirúrgica / Doutora em Ciências

The urinary bladder is a unique organ in that its normal function is storage and release of urine, and vasculature in its wall exhibits specialized features designed to accommodate changes in pressure with emptying and filling. Although we have previously described the fine details of the microvasculature of the urinary bladder of the rabbit and dog, information on the fine details of the microvasculature of the mouse bladder were deemed to be of value because of the increasing use of this species in developing genetic models for studying human disorders. The present study shows that many of the special features of the microvasculature of the mouse urinary bladder are similar to those described in the rabbit and dog, including vessel coiling, abundant collateral circulation, arterial sphincters, and a dense mucosal capillary plexus.

The urinary bladder is a unique organ in that its normal function is storage and release of urine, and vasculature in its wall exhibits specialized features designed to accommodate changes in pressure with emptying and filling. Although we have previously described the fine details of the microvasculature of the urinary bladder of the rabbit and dog, information on the fine details of the microvasculature of the mouse bladder were deemed to be of value because of the increasing use of this species in developing genetic models for studying human disorders. The present study shows that many of the special features of the microvasculature of the mouse urinary bladder are similar to those described in the rabbit and dog, including vessel coiling, abundant collateral circulation, arterial sphincters, and a dense mucosal capillary plexus.

The urinary bladder is an unusual organ in that its normal function includes filling and emptying with alternating changes in internal pressure. Although fluctuations in blood flow to the bladder wall are known to accompany these changes, detailed descriptions of the bladder microvasculature are sparse. The present study uses vascular corrosion casting and scanning electron microscopy to describe the three-dimensional anatomy of the microvasculature of the urinary bladder of the dog. Specialized features of that microvasculature, including collateral circulation, vessel folding, vessel orientation, the presence of valves and sphincters, and mucosal capillary density, that may enhance and control blood flow during normal bladder function, are described and discussed.

Background: Prostate cancer is the most prevalent form of cancer affecting men.In case of biochemical recurrence, positron emission tomography (PET) targeting prostate-specific membrane antigen (PSMA) on prostate tumor cells is primarily used, in combination with computed tomography (CT), for detection and localization of recurrence. Research for optimizing a PSMA-ligand with high affinity for tumor cells and minimal excretion to the urinary bladder is constantly ongoing, in order to allow better evaluation of the prostate and nearby regions. One such ligand is 18F-PSMA-1007, which was expected to be excreted in the urinary bladder at a rate of 5-10%. However, after switching from diagnostic to low-dose CT, the elimination of 18F-PSMA-1007 in the bladder was higher than expected. Purpose: To evaluate whether hydration during the accumulation period could affect the activity concentration in the bladder. Materials and Methods: The study involved analyzing PET-CT scans obtained from two prostate cancer patient groups who underwent 18F-PSMA-1007-PET with low-dose CT. The groups consisted of 20 participants each, with one group hydrating during the tracer’s accumulation time, while scans from the comparison group were obtained from a time point where patients did not receive instructions about water intake. The amount of radioactivity was measured by placing a standardized 3.00 cm Volume of Interest (VOI) on the bladder, which was then adjusted based on the individual size and shape of the patients' bladder. From the VOI, a standardized uptake value (SUV) was determined, which can be represented as either SUVmean or SUVmax. These values represent the average tracer concentration within a VOI and the highest concentration of the tracer in the urinary bladder, respectively. Results: SUV in the urinary bladder was lower for the hydrated group, where the SUVmean was 1,55 vs 4,5 (p=0,011) for the non-hydrated group. Similar values were obtained for SUVmax, 2,3 vs 6,65 (p&lt; 0,003). Conclusion: This retrospective study suggests that water intake during the accumulation period leads to significantly lower activity concentration in the bladder among these patients, which benefits the detection of recurrences in adjacent areas.

The urinary bladder is especially subject to infection by virtue of its direct connection to the external urethral opening, and it is natural to anticipate the presence of a well-developed immunological mechanism to respond to this potential threat. The present study describes small, very highly vascular lymph nodes located in the wall of the rabbit bladder, which may be involved in a local response to foreign antigens. The vasculature and structure of these lymph nodes was described using a combination of vascular corrosion casting, ink injection, and light and electron microscopy. The distal abdominal aorta was cannulated, and after clearing the bladder vasculature with buffered saline, one of the following procedures was used: 1) the bladder was perfuse-fixed in preparation for light and electron microscopy; 2) the bladder vasculature was filled with India ink for vessel tracing; or 3) vascular corrosion casts of the vasculature were prepared by infusing resin comprised of a mixture of Mercox, methyl methacrylate monomer, and catalyst. The resulting casts were cleaned with KOH, formic acid, and water in preparation for scanning electron microscopy. Vascular casts and India ink injections revealed the presence of a number of isolated capillary tufts consisting of clusters of one to five 'glomeruli,' closely associated with the major vesicular vessels along the lateral walls of the bladder, and supplied by tertiary branches of these vessels. Light and electron microscopy showed that the capillary tufts represented the blood supply to small, ovoid lymph nodes located near the serosal surface of the bladder wall and usually restricted to the basal half of the bladder. These nodes were encapsulated and exhibited subcapsular sinuses, numerous small blood vessels, a limited number of high endothelial cells, and, occasionally, nerves and a follicular substructure. The nodes contained abundant lymphocytes, stellate stromal cells, macrophages, and eosinophils, but lacked the obvious cortical and medullary organization and germinal centers often seen in larger lymph nodes. Vascular corrosion casts, vascular ink injections, and microscopic examination confirmed the presence of small, highly vascular lymph nodes closely associated with the main vesicular vessels along the lateral walls of the rabbit bladder. A follicular substructure of the nodes appears to correspond with the 'glomerular' capillary arrangement within the nodes as seen with corrosion casts. The rich blood supply may be indicative of the high metabolic demand of lymphatic tissue, and may be altered in response to the level of activity of the node. The close association between the lymphatic tissue and the rich blood supply to the nodes may allow a rapid mobilization of lymphocytes during a local immune response to foreign agents.