Switch to Sirolimus-based immunosuppresion in stable renal transplant recipients

Purpose: Sirolimus (SRL) has been used to replace calcineurin inhibitors (CNI) for various indications including CNI-induced toxicity. The aim of this study was to evaluate the efficacy and safety of switching from CNI to SRL in stable renal transplant recipients (RTR) with low grade proteinuria (<1 g/24 h). Methods and materials: Between 2001 and 2007, 41 patients (20 females, 21 males; mean age 47 ± 13) were switched after a median time post-transplantation of 73.5 months (range 0.2-273.2 months). Indications for switch were CNI nephrotoxicity (39%), thrombotic micro-angiopathy (14.6%), post-transplantation cancer (24.4%), CNI neurotoxicity (7.4%), or others (14.6%). Mean follow-up after SRL switch was 23.8±16.3 months. Mean SRL dosage and through levels were 2.4 ± 1.1 mg/day and 8 ± 2.2 ug/l respectively. Immunosuppressive regiments were SRL + mycophenolate mofetil (MMF) (31.7%), SRL + MMF + prednisone (36.58%), SRL + prednisone (19.51%), SRL + Azathioprine (9.75%), or SRL alone (2.43%). Results: Mean creatinine decreased from 164 to 143 μmol/l (p <0.03), mean estimated glomerular filtration rate (eGFR) increased significantly from 50.13 to 55.01 ml/minute (p <0.00001), mean systolic and diastolic blood pressure decreased from 138 to 132 mm Hg (p <0.03) and from 83 to78 mm Hg (p <0.01), but mean proteinuria increased from 0.21 to 0.63 g/24 h (p <0.001). While mean total cholesterolemia didn't increased significantly from 5.09 to 5.56 mmol/l (p = 0.06). The main complications after SRL switch were dermatitis (19.5%), urinary tract infections (24.4%), ankle edema (13.3%), and transient oral ulcers (20%). Acute rejection after the switch occurred in 7.3% of patients (n = 3), and 2 acute rejections were successfully treated with corticosteroids and 1 did not respond to treatment (not related to switch). SRL had to be discontinued in 17% of patients (2 nephrotic syndromes, 2 severe edema, 1 acute rejection, 1 thrombotic micro-angiopathy, and 1 fever). Conclusion: In conclusion, we found that switching from CNI to SRL in stable RTR was safe and associated with a significant improvement of renal function and blood pressure. Known side-effects of SRL led to drug discontinuation in less than 20% of patients and the acute rejection rate was 7.3%. This experience underlines the importance of patient selection before switching to SRL, in particular regarding preswitch proteinuria.

Prenatal diagnosis of urinary malformations: results in a series of 93 consecutive cases.

OBJECTIVE: To evaluate the pertinence of prenatal diagnosis in cases of congenital uropathy. STUDY DESIGN: Retrospective evaluation over a period of 6.5 years. METHOD: 93 cases were involved in the comparison of prenatal ultrasonographic diagnosis with neonatal findings, autopsy results, and follow-up data. RESULTS: 33 fetuses had renal parenchymal lesions, 44 had excretory system lesions, and 6 had bladder and/or urethral lesions. Seventy-three pregnancies lead to live births. Eighteen terminations of pregnancy were performed on the parents' request for extremely severe malformations. Two intrauterine deaths were observed, and two infants died in the postnatal period. Prenatal diagnosis was obtained at an average of 27 weeks gestation. Diagnostic concordance was excellent in 82% and partial in 12% of cases with renal parenchymal lesions; the false-positive rate was 6%. For excretory system lesions, concordance was excellent in 87% and partial in 7.4% of cases, with a false-positive rate of 5.6%. Finally, concordance was excellent in 100% of cases of bladder and/or urethral lesions. The overall rate of total concordance was 86%. Partial concordance cases consisted of malformations different from those previously diagnosed, but prenatal diagnosis nevertheless lead to further investigations in the neonatal period and to proper management. The false-positive diagnoses (5.4%) never lead to termination of pregnancy. CONCLUSION: Prenatal diagnosis of congenital uropathy is effective. A third-trimester ultrasonographic examination is necessary to ensure proper neonatal management, considering that the majority of cases are diagnosed at this gestational age.

Experiencia en nefrectomía: serie de casos de cuatro años

Introducción: Las indicaciones por las cuales un paciente requiere una nefrectomía son múltiples: las neoplasias, la hidronefrosis y la exclusión funcional son las principales. En manos expertas la nefrectomía es un procedimiento seguro, especialmente porque en la actualidad el abordaje por excelencia es realizar una técnica mínimamente invasiva con conservación de nefronas. Se presenta el análisis de la experiencia en Mederi, Hospital Universitario Mayor en esta intervención. Metodología: Se realizó una serie de casos de pacientes llevados a nefrectomía entre mayo de 2008 y mayo de 2012. Se incluyeron la totalidad de los casos. Resultados: Se analizaron 72 registros, 49 mujeres y 25 hombres; 13 de ellas fueron laparoscópicas. La edad promedio fue de 58,6 años. El tiempo medio operatorio fue 169,23 minutos (118-220 minutos). El sangrado operatorio promedio fue de 680,63 ml (IC95%: 2,83-1358 ml). El tiempo de hospitalización promedio fue de 4,88 días IC95%. La mayoría de los pacientes se distribuyeron en estadios medios de la enfermedad tumoral, con poco compromiso ganglionar y metástasis; el diagnóstico histológico y estadio dominante fueron el carcinoma de células renales grado 3 de Fuhrman respectivamente. Se reportan 13 casos de compromiso de la capsula de Gerota y 11 con compromiso del hilio. Discusión: La experiencia en nefrectomía de la institución es muy positiva por el bajo número de mortalidad y complicaciones. En cuanto a la técnica, es importante promover la técnica laparoscópica

Toxina botulínica en manejo de síntomas del tracto urinario bajo en pacientes con hiperplasia prostática benigna - revisión sistemática de la literatura

Revisión sistemática de la literatura tomando ensayos clínicos aleatorizados sobre el uso de la inyección intraprostática de la toxina botulínica en los pacientes con hiperplasia prostática benigna evaluando una escala validada de síntomas del tracto urinario bajo como desenlace primario

New scientific paradigms for probiotics and prebiotics

The inaugural meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP) was held May 3 to May 5 2002 in London, Ontario, Canada. A group of 63 academic and industrial scientists from around the world convened to discuss current issues in the science of probiotics and prebiotics. ISAPP is a non-profit organization comprised of international scientists whose intent is to strongly support and improve the levels of scientific integrity and due diligence associated with the study, use, and application of probiotics and prebiotics. In addition, ISAPP values its role in facilitating communication with the public and healthcare providers and among scientists in related fields on all topics pertinent to probiotics and prebiotics. It is anticipated that such efforts will lead to development of approaches and products that are optimally designed for the improvement of human and animal health and well being. This article is a summary of the discussions, conclusions, and recommendations made by 8 working groups convened during the first ISAPP workshop focusing on the topics of: definitions, intestinal flora, extra-intestinal sites, immune function, intestinal disease, cancer, genetics and genomics, and second generation prebiotics. Humans have evolved in symbiosis with an estimated 1014 resident microorganisms. However, as medicine has widely defined and explored the perpetrators of disease, including those of microbial origin, it has paid relatively little attention to the microbial cells that constitute the most abundant life forms associated with our body. Microbial metabolism in humans and animals constitutes an intense biochemical activity in the body, with profound repercussions for health and disease. As understanding of the human genome constantly expands, an important opportunity will arise to better determine the relationship between microbial populations within the body and host factors (including gender, genetic background, and nutrition) and the concomitant implications for health and improved quality of life. Combined human and microbial genetic studies will determine how such interactions can affect human health and longevity, which communication systems are used, and how they can be influenced to benefit the host. Probiotics are defined as live microorganisms which, when administered in adequate amounts confer a health benefit on the host.1 The probiotic concept dates back over 100 years, but only in recent times have the scientific knowledge and tools become available to properly evaluate their effects on normal health and well being, and their potential in preventing and treating disease. A similar situation exists for prebiotics, defined by this group as non-digestible substances that provide a beneficial physiological effect on the host by selectively stimulating the favorable growth or activity of a limited number of indigenous bacteria. Prebiotics function complementary to, and possibly synergistically with, probiotics. Numerous studies are providing insights into the growth and metabolic influence of these microbial nutrients on health. Today, the science behind the function of probiotics and prebiotics still requires more stringent deciphering both scientifically and mechanistically. The explosion of publications and interest in probiotics and prebiotics has resulted in a body of collective research that points toward great promise. However, this research is spread among such a diversity of organisms, delivery vehicles (foods, pills, and supplements), and potential health targets such that general conclusions cannot easily be made. Nevertheless, this situation is rapidly changing on a number of important fronts. With progress over the past decade on the genetics of lactic acid bacteria and the recent, 2,3 and pending, 4 release of complete genome sequences for major probiotic species, the field is now armed with detailed information and sophisticated microbiological and bioinformatic tools. Similarly, advances in biotechnology could yield new probiotics and prebiotics designed for enhanced or expanded functionality. The incorporation of genetic tools within a multidisciplinary scientific platform is expected to reveal the contributions of commensals, probiotics, and prebiotics to general health and well being and explicitly identify the mechanisms and corresponding host responses that provide the basis for their positive roles and associated claims. In terms of human suffering, the need for effective new approaches to prevent and treat disease is paramount. The need exists not only to alleviate the significant mortality and morbidity caused by intestinal diseases worldwide (especially diarrheal diseases in children), but also for infections at non-intestinal sites. This is especially worthy of pursuit in developing nations where mortality is too often the outcome of food and water borne infection. Inasmuch as probiotics and prebiotics are able to influence the populations or activities of commensal microflora, there is evidence that they can also play a role in mitigating some diseases. 5,6 Preliminary support that probiotics and prebiotics may be useful as intervention in conditions including inflammatory bowel disease, irritable bowel syndrome, allergy, cancer (especially colorectal cancer of which 75% are associated with diet), vaginal and urinary tract infections in women, kidney stone disease, mineral absorption, and infections caused by Helicobacter pylori is emerging. Some metabolites of microbes in the gut may also impact systemic conditions ranging from coronary heart disease to cognitive function, suggesting the possibility that exogenously applied microbes in the form of probiotics, or alteration of gut microecology with prebiotics, may be useful interventions even in these apparently disparate conditions. Beyond these direct intervention targets, probiotic cultures can also serve in expanded roles as live vehicles to deliver biologic agents (vaccines, enzymes, and proteins) to targeted locations within the body. The economic impact of these disease conditions in terms of diagnosis, treatment, doctor and hospital visits, and time off work exceeds several hundred billion dollars. The quality of life impact is also of major concern. Probiotics and prebiotics offer plausible opportunities to reduce the morbidity associated with these conditions. The following addresses issues that emerged from 8 workshops (Definitions, Intestinal Flora, Extra-Intestinal Sites, Immune Function, Intestinal Disease, Cancer, Genomics, and Second Generation Prebiotics), reflecting the current scientific state of probiotics and prebiotics. This is not a comprehensive review, however the study emphasizes pivotal knowledge gaps, and recommendations are made as to the underlying scientific and multidisciplinary studies that will be required to advance our understanding of the roles and impact of prebiotics, probiotics, and the commensal microflora upon health and disease management.

Morphometric analysis of the urethra of castrated female rats treated with tamoxifen

Objectives: The aim of this study was to evaluate the effects of tamoxifen on the weight and thickness of the urethral epithelium of castrated female rats. Methods: Forty castrated adult female Wistar-Hannover rats were randomly divided into two groups: Group I (n = 20) in which the animals received only the vehicle (propylene glycol) and Group 11 (n = 20) in which the rats received tamoxifen 250 mu g/day by gavage. After 30 days of treatment, all animals were sacrificed and the urethra was immediately removed for weighing. Next, the urethra was divided into the proximal and distal segments, which were fixed in 10% formaldehyde and submitted to routine histological techniques for morphometric study. The data were analyzed using the weighted minimum mean-square error method and Student`s t-test for two independent samples (p < 0.05). Results: There was a significant increase in the mean weight of the urethra in the rats of Group 11 compared to the control group, 32.0 +/- 2.0 mg and 22.0 +/- 1.6 mg, respectively (p < 0.001). The mean thickness of the distal urethral epithelium of the animals treated with tamoxifen was significantly greater than that of the control group, 42.8 +/- 2.0 mu m and 36.6 +/- 1.5 mu m, respectively (p < 0.001). There was no statistically significant difference between the two groups with respect to the epithelial thickness of the proximal urethra (p = 0.514). Conclusion: Treating castrated adult rats with 250 mu g/day of tamoxifen for 30 days may increase the weight of the urethra and the thickness of the distal urethral epithelium. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Biliary tract reconstruction using jejunal tube: an experimental study in dogs

BACKGROUND: To physiologically reconstruct the biliary tract, Crema et al suggested the application of the Monti principle to the biliary tract, already used in humans for the urinary tract. With this technique, a jejunal segment is transversely retubularized. This study aimed to evaluate the efficacy of jejunal tube interposition between the common bile duct and duodenum in dogs.METHODS: Thirteen dogs underwent a laparoscopic common bile duct ligature, followed by a biliodigestive connection by jejunal tube interposition after one week. The levels of glutamic-pyruvic and glutamic-oxalacetic transaminases, total bilirubins, alkaline phosphatase and gamma-glutamyltransferase were assessed before surgery and thereafter weekly until euthanasia, which was performed 6 weeks after biliodigestive connection.RESULTS: Data on 9 dogs were analyzed statistically. The dogs presented with obstructive jaundice after common bile duct ligature, as confirmed by biochemical examination. They showed a statistically significant reduction in cholestasis after biliodigestive connection by jejunal tube interposition and were healthy until the end of the experiment.CONCLUSION: A statistically significant reduction was seen in total bilirubin and canalicular enzymes (alkaline phosphatase and gamma-glutamyltransferase) in the 9 dogs 6 weeks after biliodigestive conviction by jejunal tube interposition.

DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection

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

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)