J. Luptak

Gene polymorphisms in bladder cancer

In Europe, cancer of the bladder is the fourth most common cancer among men, accounting for 7% of total cancers. In the USA, bladder cancer is the fifth most common cancer in men and seventh in women. This disease is three times more common in men than in women. Several risk factors, such as cigarette smoking and occupational chemical exposure, contribute to bladder cancer development. The balance between activation and detoxification of carcinogens affects the amount of DNA damage that accumulates in cells. The entire process leading to DNA damage and subsequent repair of the damage involves a host of enzymes, many of which are polymorphic. Polymorphisms in metabolic enzyme genes and repair genes may cause alterations in protein product functions that can finally lead to genomic instability and carcinogenesis. In this article, we review the polymorphisms in a number of genes that have been found to be the modulators of bladder cancer risk. Improved understanding of the molecular biology of urothelial malignancies is helping to more clearly define the role of new prognostic indices and multidisciplinary treatment for this disease.

Disability-adjusted life years (DALYs) in general population with pelvic organ prolapse: a study based on the prolapse quality-of-life questionnaire (P-QOL)

OBJECTIVE To evaluate the impact of pelvic organ prolapse (POP) on quality of life in symptomatic and asymptomatic women. STUDY DESIGN This is a cross-sectional study in a general population of adult women. Symptomatic and asymptomatic women with POP were studied. Symptomatic women were defined as those who reported the presence/feeling of lump/bulge/pressure in the vagina and on vaginal examination had the sign of POP defined as the leading edge of the vagina wall/cervix presenting at or beyond the hymeneal remnants. All women were asked to self-complete the Prolapse Quality of life questionnaire (P-QOL) to estimate the disability-adjusted life-years (DALYs) lost due to symptomatic POP. DALYs for a symptomatic POP were calculated as the sum of the years of life lost due to premature mortality (YLL) in the population and the years lost due to disability (YLD). To determinate the optimal threshold of each P-QOL domain in relationship to the symptomatic POP population a receiver operating curve (ROC) and area under curve (AUC) analysis were used. RESULTS A total of 785 were recruited. Only 539 (68.7%) consented to participate in the study. The mean age was 47 years (range 18-82 years). The total scores for each of the P-QOL domains were found to be significantly higher in symptomatic prolapse subjects compared to asymptomatic subjects (p<0.05). Estimated DALY lost per year per 1000 women obtained were 217.0 vs 324.8, lost years of 14.5 vs 10.3 in 50 vs 60-year old women. CONCLUSION In this group of women with POP the quality of life is severely affected. The DALYs revealed lost years due to symptomatic POP.

Gender-specific external barriers to seeking care for urinary incontinence

Background Barriers to seeking care for urinary incontinence are specific, objective, external conditions that prevent incontinence sufferers from seeking treatment. The aim of this study was to compare barriers, gender, and health care disparities in incontinence sufferers. Methods Incontinent patients were recruited into a questionnaire-based cross-sectional study. The 14-item Barriers to Incontinence Care Seeking Questionnaire (BICS-Q) and the three-item International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) were used to evaluate barriers to seeking health care for urinary incontinence. Results The representative sample (n = 1014) finally included 567 adults eligible to participate in this study (response rate 55.9%). Of the 147 incontinent males, 93 (63.3%) did not seek care, and of the 420 incontinent females, 282 (67.1%) did not seek care. Untreated males had significantly higher BICS-Q scores than other patients. Risk factors for barriers were obesity (odds ratio 2.13 for females versus 0.83 for males), stress urinary incontinence (1.57 versus 9.38, respectively), and urgency urinary incontinence (2.40 versus 1.75). Conclusion The barriers to seeking care for urinary incontinence seem to be gender-specific. Obese females with urgency urinary incontinence and males with stress urinary incontinence were least likely to seek treatment.

Impact of clean intermittent catheterization on quality adjusted life years (QALYs) in spinal cord injury patients with neurogenic urinary incontinence

The impact of clean intermittent catheterization (CIC) on quality adjusted life years (QALYs) gained in adults’ spinal cord injury population with neurogenic urinary incontinence (UI).

Involvement of calcium regulating ion channels in contractility of human isolated urinary bladder

This study specified the role of several key calcium-operating ion channels in contraction/relaxation of human detrusor muscle as possible target for overactive bladder (OAB) treatment. Detrusor samples, obtained from 18 males (average age 61.5 ± 5.9 years), were investigated by organ tissue bath method with following agents: diltiazem for L-type voltage-gated calcium channels; 3-fluropyridine-4-carboxylic acid (FPCA) for Orai-STIM channels; SKF 96365-hydrochloride for transient receptor potential (TRP) channels, T-type channels and Orai-STIM channels; 2- aminoethoxydiphenyl borate (2-APB) for inositol-triphosphate receptors (IP3Rs) and Orai-STIM channels. Oxybutynin and mirabegron were tested under the same conditions as controls. Mirabegron, 2-APB and FPCA exhibited the best suppressive effect on carbachol-induced detrusor contractility. As expressed by area under the contractile curve (AUCC), 2-APB, FPCA and mirabegron have similar AUCC: 1.79, 1.73, 1.73. The highest AUCC was 3.64 for diltiazem+SKF, followed by 3.21 for diltiazem, 3.16 for SKF and 2.94 for oxybutynin. The lowest median amplitude and contraction variability is for 2-APB followed by mirabegron and FPCA. There were significant differences between: 2-APB/FPCA vs.: ditiazem, diltiazem+SKF and SKF. Summary of results suggested the principal role of IP3Rs, Orai-STIM coupling and large-conductance calcium-activated potassium channels in detrusor contraction and pointed on Orai-STIM channels as possible targets for OAB pharmacotherapy.

Orai1 protein expression and the role of calcium release‐activated calcium channels in the contraction of human term‐pregnant and non‐pregnant myometrium

This experimental in vitro study examined differences in the expression and activity of calcium release‐activated calcium (CRAC) channels of human term‐pregnant and non‐pregnant myometrium.