PapG-dependent adherence breaks mucosal inertia and triggers the innate host response.
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Mucosal pathogens differ from normal flora constituents in that they provoke a host response that upsets mucosal integrity. We investigated whether the elaboration of discrete adherence factors is sufficient to break the inertia of the mucosal barrier. PapG-mediated adherence was selected as an example, because P fimbrial expression characterizes uropathogenic Escherichia coli and because adherence starts the attack on the mucosal barrier. Patients were inoculated intravesically with transformed nonvirulent E. coli strains expressing functional P fimbriae (E. coli pap(+)) or mutant fimbriae lacking the adhesin (E. coli Delta papG). E. coli pap(+) was shown to activate the innate host response, and adherent gfp(+) bacteria were observed on excreted uroepithelial cells. E. coli Delta papG failed to trigger a response and was nonadhesive. We conclude that PapG-mediated adherence breaks mucosal inertia in the human urinary tract by triggering innate immunity and propose that this activation step differentiates asymptomatic carriage from infection. (+info)
Identification of acyloxyacyl hydrolase, a lipopolysaccharide-detoxifying enzyme, in the murine urinary tract.
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Acyloxyacyl hydrolase (AOAH) is an unusual but highly conserved lipase, previously described only in myeloid cells, that removes secondary fatty acyl chains from bacterial lipopolysaccharides (LPS) and may also act on various glycero(phospho)lipids. Deacylation by AOAH greatly reduces the ability of LPS to stimulate cells via CD14-MD-2-Toll-like receptor 4. We report here that renal cortical tubule cells produce AOAH and secrete it into urine, where it can deacylate LPS. In vitro studies revealed that proximal tubule cells secrete pro-AOAH, which can be taken up by bladder cells and processed to the heterodimeric, more enzymatically active, mature form of AOAH. AOAH can then be used by the recipient cells to deacylate LPS. The enzyme produced by proximal tubule epithelium may thus be shared with downstream cells. In addition, mature AOAH is found in the urine. We suggest that cortical tubule cells may produce and secrete AOAH to limit inflammatory responses to gram-negative bacteria throughout the urinary tract. (+info)
Toll-like receptor 4 expression and cytokine responses in the human urinary tract mucosa.
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Mucosal pathogens trigger a local innate host response by activating epithelial cells. Bacterial adherence and Toll-like receptor 4 (TLR4) signaling have been implicated as key events in this process. This study addressed the molecular basis of the epithelial response to gram-negative infection in the human urinary tract. Mucosal biopsies were obtained from kidneys, ureters, and bladders of patients undergoing urinary tract surgery, and epithelial TLR4 and CD14 expression was examined by immunohistochemistry. TLR4 was detected in epithelial cells lining the entire urinary tract and in the renal tubular epithelium. CD14, in contrast, was completely absent from the epithelial tissue. The response of the epithelial cells to infection was studied by in vitro challenge of the biopsies with uropathogenic Escherichia coli bacteria. A rapid cytokine response was observed, with production of interleukin-1beta (IL-1beta), IL-6, and IL-8 but not of IL-4 or gamma interferon. Adhering, P- or type 1-fimbriated E. coli activated IL-6 and IL-8 production more efficiently than the nonfimbriated control, as shown by cellular staining and analysis of secreted cytokines. The results demonstrate that human uroepithelial cells possess the molecular machinery needed to respond to uropathogenic E. coli. This includes recognition receptors for fimbriae and TLR4 for transmembrane signaling. We speculate that the lack of membrane-bound CD14 allows the epithelium to regulate its sensitivity to lipopolysaccharide and to discriminate between more-virulent and less-virulent strains. (+info)
VURD syndrome managed by pyelostomy.
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We report a case of VURD syndrome in a three day old neonate who was diagnosed with hydronephrosis on a prenatal ultrasound. Severe tortuosity and dilation of the upper urinary tracts in the presence of progression of hydronephrosis or a persistently elevated creatinine may favor a proximal urinary diversion rather than primary valve ablation or cutaneous vesicostomy. Because of a persistently elevated serum creatinine, a nonfunctioning kidney with grade 4/5 vesicoureteral reflux and worsening contralateral hydronephrosis despite lower tract drainage, a left cutaneous pyelostomy was performed, contralateral to the kidney involved with VURD. Postoperatively the serum creatinine stabilized at 1.0 mg/dl and decreased to 0.3 mg/dl at one month of age. (+info)
Risk of congenital anomalies detected during antenatal serum screening in women with pregestational diabetes.
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BACKGROUND: Most studies comparing women with and without pregestational diabetes mellitus have not systematically screened for fetal anomalies in early pregnancy, potentially leading to selection bias. AIM: To evaluate the risk for certain congenital anomalies in women participating in an antenatal maternal screening program. DESIGN: Retrospective cohort study. METHODS: We studied all women who underwent antenatal maternal serum screening in Ontario from 1994 to 2000. Fetal anomalies were documented antenatally by ultrasonography or at autopsy, and postnatally diagnosed birth defects were recorded after 20 weeks gestational age for all live- and stillborn affected infants. We compared the risk of open neural tube defects and urinary tract defects among women with and without pregestational diabetes. RESULTS: Of 413,219 women screened during pregnancy, 2069 (0.5%) had diabetes. Compared to non-diabetic women, the adjusted odds ratios (95%CI) for neural tube and urinary tract defects among women with diabetes were 2.5 (0.9-6.8) and 2.6 (1.4-4.9), respectively. DISCUSSION: Among women who undergo second trimester maternal serum screening, pregestational diabetes is associated with an increased risk of having a fetus with an open neural tube defect or urinary tract disorder. (+info)
Interventional uroradiology in paediatrics: a potpourri of diagnostic and therapeutic options.
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The objective of the present work is to describe the indications and application of interventional, image guided diagnostic and therapeutic procedures in the paediatric urinary tract. The different indications and techniques are listed and illustrated, comprising most established indications such as percutaneous nephrostomy, sonographic guided renal biopsy, and interventional evaluation as well as treatment of childhood renal vascular disease. Additionally, some newer applications such as echo-enhanced urosonography, interventional treatment of urinary tract stenosis, or sonographically guided catheterism for deployment of therapeutic agents are included. Though the procedures are safe and successful in general, complications may occur, and peri- and post-interventional monitoring is mandatory to insure early detection and adequate management. Sometimes additional treatment or a 2nd procedure may become necessary. In conclusion, though rather seldom indicated, image guided interventional procedures are performed successfully for diagnosis and treatment of a variety of diseases of the paediatric urinary tract. They can be considered a valuable additional modality throughout infancy and childhood that should be performed by skilled and well trained paediatric radiology staff at specialised referral centres. (+info)
Prevalence of distress and symptom severity from the lower urinary tract in men: a population-based study with the DAN-PSS questionnaire.
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BACKGROUND: Lower urinary tract symptoms (LUTS) are a common and costly public health issue. The prevalence varies greatly in published reports. The distress caused by each symptom is important to assess the primary care required before therapeutic decisions or a referral to an urologist are made. OBJECTIVES: LUTS are highly prevalent in men, but less is known regarding the distress caused by each symptom. The aim of this study was to examine symptom severity and different levels of distress using the Danish Prostatic Symptom Score (DAN-PSS) questionnaire in men affected by symptoms from the lower urinary tract. METHODS: The study included all men aged 41-81 years (n=504) that, 12 months earlier in a population-based survey, had reported stress incontinence, urgency or post-micturition dribbling in a postal questionnaire. The DAN-PSS questionnaire was used to measure severity and distress from LUTS. RESULTS: In total, 311 (80%) of the 387 responders who reported at least one symptom experienced some level of distress. The most distressing symptom overall was urinary incontinence. Nine of 10 men with storage symptoms (stress, urge and 'other' urinary incontinence) reported distress even if the symptom occurred only seldom. Moreover, two-thirds of the men with the most frequent symptom, post-micturition dribbling, characterized their symptom as moderate or severe; the most distressing voiding symptom was weak stream. In general, LUTS were well tolerated. CONCLUSION: Urge incontinence was the most distressing LUTS even when occurring only seldom. The DAN-PSS questionnaire may be a potentially useful tool for health professionals to identify patients with pronounced distress from LUTS to offer therapeutic and nursing care on the relevant level. (+info)
Urinary schistosomiasis in Zimbabwean school children: predictors of morbidity.
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BACKGROUND: The morbid effects of urinary bilharziasis are becoming more evident with the advent of sophisticated diagnostics such as ultrasound. However, such diagnosis of Schistosoma haematobium morbidity is often hampered by lack of funds, proper equipment, or training. OBJECTIVE: We performed a cross-sectional investigation of schoolchildren in a highly endemic area of east central Zimbabwe in order to assess the utility of a number of simple clinical indicators to predict Schistosoma haematobium morbidity. METHODS: Prevalence and intensity of S. haematobium infection was determined in 551 schoolchildren, with ultrasound examination of the kidneys and bladder performed on 222. The association of a number of demographic, parasitological, and clinical parameters with clinical outcome was evaluated. RESULTS: Overall, 60% of the children were infected with S. haematobium . Although lacking specificity, proteinuria and parasite eggs count best predicted bladder pathology. Presence of kidney dilation was associated with fatigue and pain upon urination, but these variables were not very sensitive. CONCLUSIONS: None of the variables assessed were ideal predictors of morbidity. However, the results suggest that a combination of inexpensive, simple indicators may allow for improved targeting of S. haematobium treatment to those with severe morbidity and better monitoring of the progress of control campaigns when more expensive diagnostic methods are not available. (+info)