Toxicogenomic activity of gemcitabine in two TP53-mutated bladder cancer cell lines: special focus on cell cycle-related genes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Prevalence and risk factors for urinary incontinence in healthy pregnant Brazilian women

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Liposomal daunorubicin and dexamethasone as a treatment for multiple myeloma - The DD protocol

Context and Objective: Lipasomial daunorubicin has been used to treat hematological malignancies, including multiple myelomo (MM). The goal was to evaluate efficacy, side-effects and toxicity of liposomal daunorubicin and dexamethasone (DD Protocol). Design and Setting: Prospective study of Sírio-Libonês, São Camilo, Brasil and Alemão Oswaldo Cruz hospitals. Methods: Twenty consecutive patients with active MM received four cycles of liposomal daunorubicin intravenously for two hours (25-30 mg/m 2/day) on three consecutive days per month, with oral dexamethasone, (10 mg every six hours) on four consecutive days three times a month. Results: The male/female ratio was 1:1 and median age 60. Nine patients were stage IIA, ten IIIA and one IIIB. The median from diagnosis to starting DD was 13 months. All patients received four cycles, except one. Fifteen had already received chemotherapy before DD. Responses of > 50% reduction in serum monoclonal paraprotein were observed in six patients after first cycle (30%), six after second (30%) and four after third (20%), while four (20%) did not obtain this. Initially, 17 patients (85%) had anemia: 12 (70%) achieved correction. Progressive disease was observed in three patients (15%), while one had minimal response, four (20%) partial and 12 (60%) complete. Hemotologlical toxicity was acceptable: three patients (15%) had neutrophils < 1,000/mm 3; none had thrombocyfopenia. Gastrointestinal toxicity was mild: nausea (10%), anorexio (15%) and no vomiting. Conclusions: This treatment has mild toxicity and good response rate. It may therefore be feasible before autologous bone marraw transplantation.

The role of membranous urethral afferent autonomic innervation in the continence mechanism after nerve sparing radical prostatectomy: a clinical and prospective study

Purpose: We evaluated the somatic and autonomic innervation of the pelvic floor and rhabdosphincter before and after nerve sparing radical retropubic prostatectomy using neurophysiological tests and correlated findings with clinical parameters and urinary continence. Materials and Methods: From February 2003 to October 2005, 46 patients with prostate cancer were enrolled in a controlled, prospective study. Patients were evaluated before and 6 months after nerve sparing radical retropubic prostatectomy using the UCLA-PCI urinary function domain and neurophysiological tests, including somatosensory evoked potential, and the pudendo-urethral, pudendo-anal and urethro-anal reflexes. Clinical parameters and urinary continence were correlated with afferent and efferent innervation of the membranous urethra and pelvic floor. We used strict criteria to define urinary continence as complete dryness with no leakage at all, not requiring any pads or diapers and with a UCLA-PCI score of 500. Patients with a sporadic drop of leakage, requiring up to 1 pad daily, were defined as having occasional urinary leakage. Results: Two patients were excluded from study due to urethral stricture postoperatively. We evaluated 44 patients within 6 months after surgery. The pudendo-anal and pudendo-urethral reflexes were unchanged postoperatively (p = 0.93 and 0.09, respectively), demonstrating that afferent and efferent pudendal innervation to this pelvic region was not affected by the surgery. Autonomic afferent denervation of the membranous urethral mucosa was found in 34 patients (77.3%), as demonstrated by a postoperative increase in the urethro-anal reflex sensory threshold and urethro-anal reflex latency (p <0.001 and 0.0007, respectively). Six of the 44 patients used pads. One patient with more severe leakage required 3 pads daily and 23 showed urinary leakage, including 5 who needed 1 pad per day and 18 who did not wear pads. Afferent autonomic denervation at the membranous urethral mucosa was found in 91.7% of patients with urinary leakage. Of 10 patients with preserved urethro-anal reflex latency 80% were continent. Conclusions: Sensory and motor pudendal innervation to this specific pelvic region did not change after nerve sparing radical retropubic prostatectomy. Significant autonomic afferent denervation of the membranous urethral mucosa was present in most patients postoperatively. Impaired membranous urethral sensitivity seemed to be associated with urinary incontinence, particularly in patients with occasional urinary leakage. Damage to the afferent autonomic innervation may have a role in the continence mechanism after nerve sparing radical retropubic prostatectomy.

Desenvolvimento e avaliação de um modelo de assistência contínuo, paliativo e domiciliar a pacientes com câncer mamário ou ginecológico fora de possibilidade de cura

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Urinary flow in children: correlation with age, body height and body surface area

Peak flow rate data (Qmax) are important for diagnosis of lower urinary tract obstruction. However, the lack of uroflowmetry studies in children, makes their interpretation difficult. With this aim, we studied 167 boys classified in four groups according to their age (G1: n = 48, 6-7 years; G2: n = 43, 8-9 years; G3: n = 37, 10-11 years; G4: n = 39, 12-14 years). We studied in all children, weight, height, body surface area, peak flow rate (Qmax) and the correspondant urinary volume (Vol). Means and standard deviations of Qmax (ml/sec) were: 15 +/- 5 (G1), 15 +/- 5 (G2), 17 +/- 5 (G3) and 22 +/- 7 (G4) respectively. Corresponding urinary volumes (Vol) (mean standard deviation-in ml) were: G1 = 123 +/- 75; G2 = 122 +/- 79; G3 = 158 +/- 96 and G4 = 162 +/- 101. We found a significant correlation (p < 0,01) between Qmax and Vol in groups G2, G3 and G4; and between Qmax and height in groups G1 and G4. The authors demonstrated a positive correlation between maximum flow and voided volume, and an increase of Qmax with age.

Efeitos das formulações nanoestruturadas de doxorrubicina e cisplatina em dispersão de óxido de grafeno reduzido no tratamento da progressão do câncer de bexiga Não-músculo invasivo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comportamento materno e câncer de bexiga urinária: implicações da modulação de eixos hormonais e receptores de esteroides na fisiopatologia de lesões neoplásicas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Caracterização de sorotipos em linhagens do gênero Salmonella isoladas de diferentes afecções em animais domésticos

Foram caracterizados os sorotipos, o perfil de sensibilidade microbiana e os achados clínico-epidemiológicos em 53 linhagens do gênero Salmonella isoladas de 41 cães, nove equinos e três bovinos, acometidos por diferentes manifestações clínicas entre 1997 e 2007. Salmonella Typhimurium (45,3%), Salmonella enterica (22,6%), Salmonella Enteritidis (7,5%), Salmonella enterica subsp enterica 4,5,12i (5,7%), Salmonella Newport (5,7%), Salmonella Dublin (3,8%), Salmonella Agona (3,8%), Salmonella Glostrup (3,8%), Salmonella Saintpaul (1,8%) foram os sorotipos encontrados. Ciprofloxacina (100,0%), norfloxacina (100,0%) e gentamicina (100,0%) foram os antimicrobianos mais efetivos, enquanto a maior resistência das linhagens foi observada para ceftiofur (28,5%) e florfenicol (7,0%). As linhagens foram isoladas de animais com enterite, infecção do trato urinário, septicemia, piometra, pneumonia e conjuntivite. Ressalta-se para o predomínio do sorovar Typhimurium nas diferentes manifestações da salmonelose nos animais. Destaca-se, também, a identificação de sorotipos nos animais que também são observados em casos de salmonelose em humanos

Infecção em idosos internados em instituição de longa permanência

OBJETIVO: Avaliar ocorrência de infecção em idosos de instituição de longa permanência (ILP) durante 13 meses consecutivos. MÉTODOS: Cinqüenta e cinco idosos foram avaliados segundo critérios de infecção e de comunicação padronizada. RESULTADOS: A idade mediana foi de 75 (66-81) anos. O conjunto de dados constituiu-se de 20.896 pacientes-dia (PD) durante o período, com um total de 76 infecções para uma taxa média de infecção de 3,2 por 1000 PD. A taxa de pacientes com infecção foi de 63,6%. As topografias prevalentes foram respiratória (50%), trato urinário (32%), pele e partes moles (12%) e gastrintestinal (7%), com taxa de infecção/1000 PD de 1,60; 1,01; 0,38; e 0,2, respectivamente. A taxa de mortalidade por infecção foi de 5%. Agentes microbiológicos foram isolados em 30,5% dos episódios infecciosos e Escherichia coli e Staphylococcus aureus foram os mais freqüentes. CONCLUSÃO: Infecção apresentou elevada incidência nos idosos institucionalizados, porém nenhum evento extraordinário foi observado.

Complications and risk factors in transrectal ultrasound-guided prostate biopsies

CONTEXTO E OBJETIVO: A biópsia da próstata não é um procedimento isento de riscos. Existe preocupação com respeito às complicações e quais seriam os melhores antibióticos usados antes do procedimento. O objetivo foi determinar a taxa de complicações e os possíveis fatores de risco para complicação na biópsia da próstata. TIPO DE ESTUDO E LOCAL: Estudo prospectivo clínico, realizado no Hospital das Clínicas de Botucatu. MÉTODOS: Foram realizadas biópsias em 174 pacientes que apresentavam anormalidade ao exame digital da próstata ou antígeno prostático específico maior que 4 ng/ml ou ambos. Todos os pacientes realizaram enema e antibioticoprofilaxia previamente ao exame. As complicações foram anotadas após o término do procedimento e em consultas posteriores. Algumas condições foram investigadas como possíveis fatores de risco para biópsias de próstata: idade, câncer da próstata, diabetes melito, hipertensão arterial sistêmica, antecedentes de prostatite, uso de ácido acetilsalicílico, volume prostático, número de biópsias e uso de sonda vesical. RESULTADOS: As complicações hemorrágicas foram mais comuns (75,3%) enquanto que as infecciosas ocorreram em 19% dos casos. O tipo mais freqüente foi a hematúria, ocorrendo em 56% dos pacientes. A infecção do trato urinário ocorreu em 16 pacientes (9,2%). Sepse foi observada em três pacientes (1,7%). Não houve óbitos. em 20% dos pacientes não foram observadas complicações após o exame. A presença da sonda vesical foi fator de risco para complicações infecciosas (p < 0,05). O número maior de amostras nas biópsias foi relacionado à hematúria, sangramento retal e complicações infecciosas (p < 0,05). As demais condições investigadas não se relacionaram com complicações pós-biópsia da próstata. CONCLUSÕES: As complicações pós-biópsia da próstata foram em sua maioria autolimitadas. A taxa de complicações graves foi baixa, sendo a biópsia de próstata guiada pelo ultra-som segura e eficaz. A retirada de um maior número de fragmentos na biópsia relaciona-se com hematúria, sangramento retal e complicações infecciosas. A sonda vesical foi um fator de risco para complicações infecciosas.

Factors predictive of inappropriateness in requests for parenteral antimicrobials for therapeutic purposes: A study in a small teaching hospital in Brazil

Background: The identification of patterns of inappropriate antimicrobial prescriptions in hospitals contributes to the improvement of antimicrobial stewardship programs (ASP). Methods: We conducted a cross-sectional study to identify predictors of inappropriateness in requests for parenteral antimicrobials (RPAs) in a teaching hospital with 285 beds. We reviewed 25% of RPAs for therapeutic purposes from y 2005. Appropriateness was evaluated according to current guidelines for antimicrobial therapy. We assessed predictors of inappropriateness through univariate and multivariate models. RPAs classified as 'appropriate' or 'probably appropriate' were selected as controls. Case groups comprised inappropriate RPAs, either in general or for specific errors. Results: Nine hundred and sixty-three RPAs were evaluated, 34.6% of which were considered inappropriate. In the multivariate analysis, general predictors of inappropriateness were: prescription on week-ends/holidays (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.20-2.28, p = 0.002), patient in the intensive care unit (OR 1.57, 95% CI 1.11-2.23, p = 0.01), peritoneal infection (OR 2.15, 95% CI 1.27-3.65, p = 0.004), urinary tract infection (OR 1.89, 95% CI 1.25 -2.87, p = 0.01), combination therapy with 2 or more antimicrobials (OR 1.72, 95% CI 1.15-2.57, p = 0.008) and prescriptions including penicillins (OR 2.12, 95% CI 1.39-3.25, p = 0.001) or 1(st) generation cephalosporins (OR 1.74, 95% CI 1.01-3.00, p = 0.048). Previous consultation with an infectious diseases (ID) specialist had a protective effect against inappropriate prescription (OR 0.34, 95% CI 0.24-0.50, p < 0.001). Factors independently associated with specific prescription errors varied. However, consultation with an ID specialist was protective against both unnecessary antimicrobial use (OR 0.04, 95% CI 0.01-0.26, p = 0.001) and requests for agents with an insufficient antimicrobial spectrum (OR 0.14, 95% CI 0.03-0.30, p = 0.01). Conclusions: Our results demonstrate the importance of previous consultation with an ID specialist in assuring the quality of prescriptions. Also, they highlight prescription patterns that should be approached by ASP policies.

Resultado perinatal de fetos com malformações do trato urinário

PURPOSE: to evaluate the perinatal outcome of fetuses with congenital anomalies of the urinary tract. METHODS: we reviewed the perinatal outcome of 35 fetuses with congenital anomalies of the urinary tract. The following characteristics related to the uropathy were analyzed: type (hydronephrosis, dysplasia and renal agenesis), side of lesion (bilateral or unilateral), and level of the obstruction (high or low, in hydronephrosis). The perinatal outcome was evaluated according to these characteristics. The data were analyzed by the c² test and by the exact Fisher test. The level of significance was 0.05. RESULTS: the incidence of hydronephrosis was 68.6%. Half of the fetuses had unilateral hydronephrosis. Renal dysplasia occurred in 17.1% of the cases; 83.3% of these were bilateral and 16.7%, unilateral. The incidence of renal agenesis was 14.3%, all bilateral. The fetuses with dysplasia/agenesis had a 91% incidence of oligohydramnios, preterm birth, low birth weight, and death. In the group with bilateral disease the presence of oligohydramnios, preterm birth, low birth weight, death, urinary tract infections, and the need of hospitalization for a period greater than 7 days was significant when compared to the group with unilateral disease. The need of hospitalization for a period greater than 7 days in patients with low obstruction was significantly higher when compared to the patients with high obstruction. CONCLUSIONS: hydronephrosis, bilateral disease, and lower obstruction were the most frequent uropathies. The dysplasia/agenesis group had a worse prognosis when compared with the hydronephrosis group. Bilateral disease had a worse prognosis when compared with the unilateral disease group. In the low obstruction group, the need for a period of hospitalization greater than seven days was higher than in the high obstruction group.

Amitriptyline aggravates the fibrosis process in a rat model of infravesical obstruction

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Fatores associados à recorrência da infecção do trato urinário em crianças

OBJETIVOS: verificar a freqüência de infecção urinária recorrente (ITU) e avaliar os fatores associados à recorrência da ITU em crianças. MÉTODOS: estudo retrospectivo de 95 pacientes com seguimento de um ano (68 meninas e 27 meninos, mediana de idade três anos). As variáveis estudadas foram: sexo, idade, febre, constipação, tipo de bactéria, refluxo vésico-ureteral (RVU), anormalidades na cintilografia renal com ácido dimercaptosuccínico (DMSA). RESULTADOS: infecção urinária recorrente ocorreu em 49,5% crianças (19 com trato urinário normal, 19 com RVU e 9 com estenose da junção pielocalicial). Comparando o grupo com ITU recorrente com o grupo sem ITU recorrente não se encontrou diferença significativa entre sexos, presença de febre, constipação e anormalidades na cintilografia renal com DMSA. A ITU recorrente foi significativamente maior nas crianças com um ano ou menos, naquelas menores de dois anos com RVU, nas com bactéria diferente da Escherichia coli e sem profilaxia antibacteriana. Os fatores de risco significativos para a recorrência ITU foram idade < 2 anos (OR = 3,83) e refluxo vésico-ureteral (OR = 4,95). CONCLUSÕES: por causa da elevada freqüência de ITU recorrente é importante o seguimento regular de grupo de crianças com fatores de risco para ITU recorrente.