Using Mitrofanoff's principle and Monti's technique as a surgical option for bladder augmentation with a continent stoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hydronephrosis, reflux and renal failure are serious complications that occur in patients with neurogenic bladder associated with myelomeningocele. When the bladder compliance is lost, it is imperative to carry out surgery aimed at reducing bladder storage pressure. An ileocystoplasty, and for patients not suitable for intermittent catheterization, using the Mitrofanoff principle to form a continent stoma and the subsequent closure of the bladder neck, can be used. We report here, for the first time to the best of our knowledge, an association between two previously described techniques (the Mitrofanoff principle and the technique of Monti), that can solve the problem of a short appendix in obese patients.</p> <p>Case presentation</p> <p>A 33-year-old male Caucasian patient with myelomeningocele and neurogenic bladder developed low bladder compliance (4.0 mL/cm H₂O) while still maintaining normal renal function. A bladder augmentation (ileocystoplasty) with continent derivation principle (Mitrofanoff) was performed. During surgery, we found that the patient's appendix was too short and was insufficient to reach the skin. We decided to make an association between the Mitrofanoff conduit and the ileal technique of Monti, through which we performed an anastomosis of the distal stump of the appendix to the bladder (with an antireflux valve). Later, the proximal stump of the appendix was anastomosed to an ileal segment of 2.0 cm that was open longitudinally and reconfigured transversally (Monti technique), modeled by a 12-Fr urethral catheter, and finally, the distal stump was sutured at the patient's navel.</p> <p>After the procedure, a suprapubic cystostomy (22 Fr) and a Foley catheter (10 Fr) through the continent conduit were left in place. The patient had recovered well and was discharged on the tenth day after surgery. He remained with the Foley catheter (through the conduit) for 21 days and cystostomy for 30 days. Six months after surgery he was continent with good bladder compliance without reflux and fully adapted to catheterization through the navel.</p> <p>Conclusion</p> <p>The unpublished association between the Mitrofanoff and Monti techniques is feasible and a very useful alternative in urologic cases of derivation continent in which the ileocecal appendix is too short to reach the skin (i.e., in obese patients).</p

Endemic Dengue Associated with the Co-Circulation of Multiple Viral Lineages and Localized Density-Dependent Transmission

Dengue is one of the most important infectious diseases of humans and has spread throughout much of the tropical and subtropical world. Despite this widespread dispersal, the determinants of dengue transmission in endemic populations are not well understood, although essential for virus control. To address this issue we performed a phylogeographic analysis of 751 complete genome sequences of dengue 1 virus (DENV-1) sampled from both rural (Dong Thap) and urban (Ho Chi Minh City) populations in southern Viet Nam during the period 2003–2008. We show that DENV-1 in Viet Nam exhibits strong spatial clustering, with likely importation from Cambodia on multiple occasions. Notably, multiple lineages of DENV-1 co-circulated in Ho Chi Minh City. That these lineages emerged at approximately the same time and dispersed over similar spatial regions suggests that they are of broadly equivalent fitness. We also observed an important relationship between the density of the human host population and the dispersion rate of dengue, such that DENV-1 tends to move from urban to rural populations, and that densely populated regions within Ho Chi Minh City act as major transmission foci. Despite these fluid dynamics, the dispersion rates of DENV-1 are relatively low, particularly in Ho Chi Minh City where the virus moves less than an average of 20 km/year. These low rates suggest a major role for mosquito-mediated dispersal, such that DENV-1 does not need to move great distances to infect a new host when there are abundant susceptibles, and imply that control measures should be directed toward the most densely populated urban environments

Emergence of the Asian 1 Genotype of Dengue Virus Serotype 2 in Viet Nam: In Vivo Fitness Advantage and Lineage Replacement in South-East Asia

A better description of the extent and structure of genetic diversity in dengue virus (DENV) in endemic settings is central to its eventual control. To this end we determined the complete coding region sequence of 187 DENV-2 genomes and 68 E genes from viruses sampled from Vietnamese patients between 1995 and 2009. Strikingly, an episode of genotype replacement was observed, with Asian 1 lineage viruses entirely displacing the previously dominant Asian/American lineage viruses. This genotype replacement event also seems to have occurred within DENV-2 in Thailand and Cambodia, suggestive of a major difference in viral fitness. To determine the cause of this major evolutionary event we compared both the infectivity of the Asian 1 and Asian/American genotypes in mosquitoes and their viraemia levels in humans. Although there was little difference in infectivity in mosquitoes, we observed significantly higher plasma viraemia levels in paediatric patients infected with Asian 1 lineage viruses relative to Asian/American viruses, a phenotype that is predicted to result in a higher probability of human-to-mosquito transmission. These results provide a mechanistic basis to a marked change in the genetic structure of DENV-2 and more broadly underscore that an understanding of DENV evolutionary dynamics can inform the development of vaccines and anti-viral drugs

Dengue Virus Infection and Virus-Specific HLA-A2 Restricted Immune Responses in Humanized NOD-scid IL2rγnull Mice

BACKGROUND:The lack of a suitable animal model to study viral and immunological mechanisms of human dengue disease has been a deterrent to dengue research. METHODOLOGY/PRINCIPAL FINDINGS:We sought to establish an animal model for dengue virus (DENV) infection and immunity using non-obese diabetic/severe combined immunodeficiency interleukin-2 receptor gamma-chain knockout (NOD-scid IL2rgamma(null)) mice engrafted with human hematopoietic stem cells. Human CD45(+) cells in the bone marrow of engrafted mice were susceptible to in vitro infection using low passage clinical and established strains of DENV. Engrafted mice were infected with DENV type 2 by different routes and at multiple time points post infection, we detected DENV antigen and RNA in the sera, bone marrow, spleen and liver of infected engrafted mice. Anti-dengue IgM antibodies directed against the envelope protein of DENV peaked in the sera of mice at 1 week post infection. Human T cells that developed following engraftment of HLA-A2 transgenic NOD-scid IL2rgamma(null) mice with HLA-A2(+) human cord blood hematopoietic stem cells, were able to secrete IFN-gamma, IL-2 and TNF-alpha in response to stimulation with three previously identified A2 restricted dengue peptides NS4b 2353((111-119)), NS4b 2423((181-189)), and NS4a 2148((56-64)). CONCLUSIONS/SIGNIFICANCE:This is the first study to demonstrate infection of human cells and functional DENV-specific T cell responses in DENV-infected humanized mice. Overall, these mice should be a valuable tool to study the role of prior immunity on subsequent DENV infections

STAT2 Mediates Innate Immunity to Dengue Virus in the Absence of STAT1 via the Type I Interferon Receptor

Dengue virus (DENV) is a mosquito-borne flavivirus, and symptoms of infection range from asymptomatic to the severe dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). High viral loads correlate with disease severity, and both type I & II interferons (IFNs) are crucial for controlling viral replication. We have previously reported that signal transducer and activator of transcription (STAT) 1-deficient mice are resistant to DENV-induced disease, but little is known about this STAT1-independent mechanism of protection. To determine the molecular basis of the STAT1-independent pathway, mice lacking STAT1, STAT2, or both STAT1 and STAT2 were infected with a virulent mouse-adapted strain of DENV2. In the first 72 hours of infection, the single-deficient mice lacking STAT1 or STAT2 possessed 50–100 fold higher levels of viral RNA than wild type mice in the serum, spleen, and other visceral tissues, but remained resistant to DENV-induced death. In contrast, the double-deficient mice exhibited the early death phenotype previously observed in type I and II IFN receptor knockout mice (AG129), indicating that STAT2 is the mediator of the STAT1-independent host defense mechanism. Further studies demonstrated that this STAT2-dependent STAT1-independent mechanism requires the type I IFN receptor, and contributes to the autocrine amplification of type I IFN expression. Examination of gene expression in the spleen and bone marrow-derived macrophages following DENV infection revealed STAT2-dependent pathways can induce the transcription of a subset of interferon stimulated genes even in the absence of STAT1. Collectively, these results help elucidate the nature of the poorly understood STAT1-independent host defense mechanism against viruses by identifying a functional type I IFN/STAT2 signaling pathway following DENV infection in vivo

VEGF genetic polymorphisms affect the responsiveness to sildenafil in clinical and postoperative erectile dysfunction

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Vascular endothelial growth factor (VEGF) is a cytokine involved in angiogenesis and is closely related to the nitric oxide-cyclic guanosine monophosphate pathway, a target for sildenafil. We investigated for the first time whether three clinically relevant polymorphisms in the VEGF gene are associated with altered responsiveness to sildenafil treatment in postoperative erectile dysfunction (PED) and clinical erectile dysfunction (CED). We determined VEGF genotypes for three polymorphisms in VEGF promoter: -2578C4A (rs699947), -1154G4A (rs1570360) and -634G4C (rs2010963) in 126 patients with erectile dysfunction (ED; 66 patients with PED and 60 patients with CED). The patients were classified as good or poor responders to sildenafil (GR and PR groups, respectively) according to their responses with basis on the changes in five-item version of the International Index for Erectile Function (5-IIEF). We found an association of the -1154AA genotype with PR in both PED and CED patients (Po0.05), whereas the -2578AA and the -2578CA genotypes were associated with PR only in the CED group (Po0.05). The AAG haplotype was more common in PR than in GR patients (38% versus 20%, respectively; P 0.032) in the CED group, thus increasing the risk for a worse response to sildenafil (odds ratio, OR 2.33, 95% confidence interval, CI 1.07-5.09). However, this finding does not resist to Bonferroni's correction (P40.0125). Our results indicate that VEGF polymorphisms affect the responsiveness of PED and CED patients to sildenafil. These findings may help to improve the therapy of patients with ED.135437442Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq