Severity of hemorrhagic cystitis and failure of noninvasive management correlate with several identifiable risk factors. Prospective identification of patients with these risk factors may allow for targeted early intervention in those at highest risk.

No abstract

The past 30 years have seen broad changes in the diagnosis and management of vesicoureteral reflux (VUR). Recently, a clinical debate has generated an open discussion in academic circles. New evidence has shifted treatment patterns away from widespread surgical management and recently brought into question some pharmacologic treatments. VUR is usually not hazardous by itself but is a significant risk factor for urinary tract infection (UTI) and less commonly, renal scarring and insufficiency. Given the costs and morbidity of UTI as well as the potential for significant renal injury, our approach remains conservative. Careful follow-up, parental education about pathophysiology and management of VUR and UTI, and management of bowel and bladder dysfunction (BBD) when present, are the foundation of treatment. Additionally, though we recognize the limitation of continuous antibiotic prophylaxis (CAP), we believe the benefits outweigh the risks and costs for many patients. Careful observation can be considered in patients with a single medical home, parental understanding of what UTI signs and symptoms are, low grade VUR, no history of complicated UTIs and close follow-up. Surgical management remains a relevant option for select patients who fail conservative measures with breakthrough UTIs or failure to resolve. Minimally invasive surgical options are available with acceptable outcomes though open ureteroneocystostomy still carries the highest success rate.

No abstract

Several molecules that suppress metastasis without suppressing tumorigenicity have been identified, but their mechanisms of action have not yet been determined. Many block growth at the secondary site, suggesting involvement in how cells respond to signals from the extracellular milieu. Breast cancer metastasis suppressor 1 (BRMS1)–transfected MDA-MB-435 cells were examined for modifications of phosphoinositide signaling as a potential mechanism for metastasis suppression. 435/BRMS1 cells expressed <10% of phosphatidylinositol-4, 5-bisphosphate compared with parental cells, whereas levels of the PtdIns(4)P and phosphatidylinositol-3-phosphate were unchanged. Inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] were decreased in 435/BRMS1 cells by ∼50%. Phosphatidylinositol-3,4,5-trisphosphate levels were undetectable in 435/BRMS1 cells, even when stimulated by exogenous insulin or platelet-derived growth factor. Immunofluorescence microscopy to examine cellular distribution confirmed that phosphatidylinositol-4,5-bisphosphate distribution with cells was unchanged but was uniformly decreased throughout the cell. Although the gross morphology of 435/BRMS1 cells is similar to the parent, filamentous actin was more readily apparent in 435/BRMS1. Intracellular calcium, measured using Fluo-3 and Fura-2 fluorescent calcium indicator dyes, was somewhat lower, but not statistically different in 435/BRMS1 compared with parental cell. However, when stimulated with platelet-derived growth factor, MDA-MB-435 cells, but not 435/BRMS1 cells mobilized intracellular calcium. Taken together, these results implicate signaling through phosphoinositides in the regulation of breast cancer metastasis, specifically metastasis that can be suppressed by BRMS1.

No abstract

No abstract

No abstract