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To explore a new treatment strategy for urinary incontinence, human bone marrow mesenchymal stem cells (MSC) of the first in vitro passage were exposed to 5-azacytidine (AZA) to induce myogenic differentiation, and cultured for a total of six passages. Expression of stem cell surface antigens and intracellular alpha-actin was examined by flow cytometry at the end of each passage and compared to that of native MSC (not exposed to AZA) cultured in parallel. To analyze differentiation into striated muscle, expression of the transcription factor MyoD1 and myosin heavy chain (MyHC) was examined by RT-PCR. Both native and AZA-exposed MSC of all passages were negative for the progenitor/endothelial antigen CD34, leukocytic CD45, and endothelial/monocytic CD31. In contrast, the MSC markers CD73, CD90, CD105, and intracellular actin were detected in both groups of MSC throughout the culture period. After an initial increase, the expression level of MSC antigens decreased over time particularly in AZA-exposed MSC. Expression of smooth muscle alpha-actin also declined, but was greater in AZA-exposed MSC throughout the culture period. Varying percentages of MSC cultures expressed MyoD1 and MyHC mRNA. In late passages, AZA-exposed MSC tended to be more frequently positive than native MSC. In pilot experiments, transplantation of MSC into the bladder neck tissue of athymic rats was feasible; long-term analyses are pending. We conclude that independent of AZA exposure, MSC express smooth and striated muscle antigens. Treatment with AZA slightly increases myogenic differentiation, but may not be necessary in future studies of MSC as a treatment modality for urinary incontinence.

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What ' s known on the subject? and What does the study add?The prognosis of bladder cancer signifi cantly depends on tumour stage and time of diagnosis so early diagnosis is desirable to decrease mortality and treatment costs. The NMP22 test is approved for clinical application by the Food and Drug Administration (FDA) of the US. Previous studies have reported values of 47 -100% for sensitivity and 58 -91% for specifi city with this test, but there is no new data on the predictive value of NMP22 for screening bladder cancer (BC). The most important risk factor for BC is the tobacco consumption but occupational exposure to carcinogenic substances, especially aromatic amines, is regarded as another risk factor.The UroScreen study is a prospective longitudinal study for the early detection of BC. To our knowledge, it is the largest prospective validation study conducted over the longest period of time. The study results led us to conclude that, based on the currently available data, NMP22 should not be regarded as an alternative to endoscopy, and we could not make a general recommendation for screening or follow-up. The UroScreen results indicate that urine-based molecular markers could be a suitable addition to urine cytology and the detection of microhaematuria. OBJECTIVE• To evaluate the value of nuclear matrix protein-22 (NMP22) in bladder cancer (BC) screening, and its effect on variables in a prospective study in a high-risk population. PATIENTS AND METHODS• A total of 1772 chemical workers (mean age 62 years) exposed to carcinogenic aromatic amines were enrolled in the study.• In all, 7091 screening check-ups in 1609 subjects were performed.• Urine samples were collected for a quantitative NMP22 immunoassay, urine analysis and creatinine concentration assessment.• Cystoscopy and subsequent transurethral resection were performed where there were suspicious fi ndings. RESULTS• Histopathological analysis found three papillary urothelial neoplasms of low malignant potential, fi ve recurrent BCs and 13 primary BCs. Three tumours were at a muscle-invasive stage (pT2, pT3a or pT3b).• We found higher NMP22 concentrations ( > 10 U/mL) in 224 patients, which correctly predicted BC in six cases (sensitivity 97.29%, specifi city 28.57%; negative predictive value 99.04%, positive predictive value 12.24%).• Gross haematuria affected NMP22 results (odd ratio [ OR ] 3.49, 95% confi dence interval [ CI ] 1.81 -6.73). Infection also affected NMP22 results (OR 4.13,).• NMP22 was more frequently positive in urine with creatinine concentration > 2.5 g/L (OR 1.61, 95% CI 0.91 -2.86). CONCLUSIONS• NMP22 outcomes are affected by haematuria, infection and concentrated urine.• NMP22 alone cannot be recommended for primary screening in a high-risk population nor as an alternative to cystoscopy during follow-up.• A NMP22 test might be a useful adjunct to urine cytology. KEYWORDSbladder cancer , early detection , renal function , NMP22 , haematuria Study Type -Diagnostic (non-consecutive cohort without consistently applied reference st...

Limitations of current centrifugal blood pumps are related to heat generation of bearings and leakage of seals, to dead water zones, and to poor efficiency. A new concept is proposed in this paper to ameliorate these problems based on a miniaturized magnetic drive, and a prototype is introduced. The pump rotor is suspended and driven by a radial permanent magnetic field that stabilizes the impeller in 4 of the 6 spatial degrees of freedom and allows it to be top-spun on a single blood-flushed pivot bearing with minimal load and friction. A shrouded impeller with an open center and 4 logarithmically curved channels is run inside a cone-and-plate-type housing with a spiral volute chamber. In vitro testing was performed comparing this design with the BioMedicus, St. Jude, and Sarns pumps. The prototype is demonstrated to have the smallest internal volume (35 ml), surface (190 qcm), and passage time (0.5 s at 4 L/min), as well as the highest hydraulic efficiency (up to 0.4) of all devices studied.

RESULTS• As of July 2010, 15 bladder tumours were detected in 14 participants.• GH was found in four out of nine highgrade tumours and associated with a rate ratio of 3.82, 95% confidence interval (CI) 0.50-29.15 for the development of bladder lesions.• The PPV of GH was 11.4%, but only 1.2% for μ H. μ H occurred in 18.8% of urine samples and was not associated with bladder cancer [rate ratio (RR) 0.72, 95% CI 0.11-4.78].• Abundant urinary leukocytes were associated with μ H [odds ratio (OR) CONCLUSION• While the PPV of μ H for bladder cancer was low, there was a strong influence of haematuria and leukocytes on the proteinbased tumour test NMP22®.• Erythrocytes and leukocytes should be determined at least semi-quantitatively for the interpretation of positive NMP22 test results.• In addition, a panel of tumour tests that includes methods not affected by the presence of erythrocytes or leukocytes such as cytology and UroVysion TM would improve bladder cancer screening.

In present group of patients, survivin was a reliable biomarker for high-grade urothelial BC (sensitivity 83%), but not for low grade (sensitivity 35%) urothelial BC with a high specificity (88%). No confounders influencing the results of survivin measurements could be identified.

Combinations of tumour markers increased the sensitivity and NPV in the detection of recurrence of NMI TCC. A stepwise approach of tumour marker determination may be used to reduce the frequency of follow-up cystoscopies at a reasonable risk.