Effect of Dynamic Workstation Use on Radiologist Detection of Pulmonary Nodules on CT.

PURPOSE: The aim of this study was to determine the effects of using a treadmill workstation during CT interpretation on radiologists' sensitivity for lung nodule detection, accuracy and adherence to accepted management recommendations, and examination interpretation time. METHODS: This HIPAA-compliant study was approved by the institutional review board. Three radiologists performed a retrospective review of 55 CT examinations of the chest originally performed for lung cancer screening. These studies were reviewed both while sitting at a conventional workstation and while walking at a treadmill workstation. A separate thoracic radiologist reviewed the examinations at a conventional workstation only to serve as a control. The number of pulmonary nodules detected, accuracy of or adherence to follow-up recommendations, and time required for examination interpretation were recorded and compared between each condition. RESULTS: There was no statistically significant difference in the total number of nodules detected while walking versus seated. Intraobserver follow-up recommendations were consistent to highly consistent between sitting and walking. There was moderate interobserver agreement between the radiologists' recommendation for seated versus walking conditions. There was a statistically significant difference in time taken to complete each examination, with interpretation during walking taking less time than during sitting. CONCLUSIONS: Use of a treadmill workstation does not significantly affect the detection of lung nodules on CT or lead to changes in management recommendations but does decrease examination interpretation time.

Urothelial lesion formation is mediated by TNFR1 during neurogenic cystitis.

Interstitial cystitis (IC) is a chronic bladder inflammatory disease of unknown etiology that shares similarities with Crohn's disease and psoriasis. IC, often regarded as a neurogenic cystitis, is associated with urothelial lesions that likely compromise the bladder permeability barrier and thereby contribute to patient morbidity. Here, we use a murine model of neurogenic cystitis to investigate the mechanism of urothelial lesion formation and find that urothelial apoptosis induces formation of lesions. Lesions formed in wild-type mice but not in mice deficient in TNF, TNF receptors, or mast cells. In urothelial cultures, only siRNAs targeting TNFR1, but not TNFR2, blocked TNF-induced apoptosis, indicating a primary role for TNFR1. Trans-epithelial resistance, a measure of bladder barrier function, decreased during neurogenic cystitis in wild-type and TNFR2(-/-) mice but was stabilized in TNF(-/-) mice. Anti-TNF antibodies both altered bladder mast cell localization and stabilized barrier function. Based on these findings, we conclude that mast cell activation and release of TNF drive urothelial apoptosis and lesion formation in a murine neurogenic cystitis model, and we hypothesize that anti-TNF therapy may stabilize bladder barrier function in IC patients.

Induction of the urothelial differentiation program in the absence of stromal cues.

PURPOSE: The urothelial stroma is presumed to have a critical role in the formation and homeostasis of normal urothelium. To determine the intrinsic capacity of urothelial cells to initiate urothelial differentiation human urothelial cell were cultured under conditions that promote differentiation in the absence of stromal signaling. MATERIALS AND METHODS: Immortalized and primary human urothelial cells were cultured in semisolid medium. Recovered cells were then analyzed by immunofluorescence, flow cytometry and immunoblotting for expression of the differentiation specific keratins K18 and K8, and cyclin-cyclin-dependent kinase inhibitors. The expression of these markers in cells following semisolid culture was then compared with that in normal bladder and ureteral mucosa as well as in synthetic urothelium generated by 3-dimensional organotypic raft cultures. RESULTS: Organotypic raft culture of primary and immortalized urothelial cells generated full-thickness epithelium that resembled human bladder and ureteral urothelium, and expressed K8 and K18 in superficial layers. Suspension culture in semisolid medium induced K18 expression approximately 9-fold at 24 hours. p21 and p27 expression were induced by 6 hours and yet p21 expression subsided within 12 hours, while p27 expression persisted. CONCLUSIONS: These results indicate that primary and immortalized human urothelial cells have the capacity to enter the urothelial differentiation program and such entry does not require inductive signals from stroma. Furthermore, these data suggest that p21 and p27 have distinct roles in regulating the urothelial cell cycle.

Epithelial differentiation promotes the adherence of type 1-piliated Escherichia coli to human vaginal cells.

Colonization of the vaginal introitus by fecal Escherichia coli is thought to be a key initial event leading to acute urinary tract infection, yet the mannosylated receptor for type 1 pili on the squamous epithelium of vaginal mucosa is unknown. E. coli expressing type 1 pili adhered to sections of normal human vaginal epithelium in a gradient with greatest binding in upper cell layers was observed, which suggests that epithelial differentiation influences bacterial binding. Consistent with this observation, bacterial binding was enhanced in vaginal epithelial cultures that were induced to differentiate, and this enhanced bacterial binding was associated with increased K13 expression levels and increased binding of the mannose-specific lectin Galanthus nivalis agglutinin. These results demonstrate that the binding of type 1-piliated E. coli to vaginal epithelial cells correlates with epithelial differentiation and suggest that the vaginal receptor for type 1 pili is up-regulated during differentiation.