Voided Urine Samples Research Articles

Simultaneous immunostaining with anti-S100P and anti-SV40 antibodies revealed the origin of BK virus-infected decoy cells in voided urine samples.

Methods for determining the origin of BK virus (BKV)-infected cells (decoy cells) in clinical urine samples have not been established although they could enhance the diagnosis of BKV infection in immunocompromised patients. We performed simultaneous immunostaining with anti-S100P (a urothelial marker) and anti-SV40 antibodies in 66 clinical urine samples exhibiting SV40 positivity and a decoy-cell appearance on Papanicolaou staining. The clinical voided urine samples included seven cases of renal transplantation, 47 cases of cancer therapy and 12 cases of non-neoplastic disease. SurePath(™) liquid-based cytology was used for the urine samples. BKV-infected cells were categorized as SV40(+)/S100P(+) and SV40 (+)/S100p(-). SV40(+)/S100P(-) cells were found in 55 cases (83.4%); nine cases (13.6%) carried both SV40(+)/S100P(-) and SV40(+)/S100P(+) cells. The former were identified as BKV infection in renal tubules and the latter in both the renal tubules and urothelial epithelia. The remaining two cases (3.0%) had only SV40(+)/S100P(+) cells of urothelial origin. Simultaneous immunostaining with anti-S100P and anti-SV40 is a useful method for determining the origin of BKV-infected cells in clinical urine samples from immunocompromised patients such as renal transplantation recipients.

Abstract 1359: Identification of a novel hypermethylated tumor suppressor gene in human bladder cancer

Abstract Bladder cancer is the sixth most common cancer in the world and the incidence is particularly high in southwestern Taiwan. Although bladder cancer patients have a low mortality rate, long term follow-up with repeated cystoscopy is required due to the high recurrence nature of the tumor. Therefore, a non-invasive detection assay is urgently required for bladder cancer patients. Aberrant promoter hypermethylation which is considered as a hallmark of cancer for over a decade, plays an important role in controlling cancer progression. Nevertheless, detection of promoter hypermethylation in bodily fluid has been implicated as a non-invasive and sensitive tool for cancer diagnosis. We aim to identify novel markers that are hypermethylated in bladder cancer. In this regard, by using illumina 27K CpG island methylation array, we identified several novel targets that are hypermethylated in 7 bladder cancer patient samples but not in primary normal human urothelim. Combined bisulfite restriction analysis (COBRA) and bisulphite pyrosequencing confirmed the array result in bladder cancer cell lines. Further, bisulphite pyrosequencing demonstrated that a significantly higher methylation level of those targets in cancer samples with higher histological grade (P < 0.05) and pathological stage (P < 0.05). The potential of non-invasive diagnosis of bladder cancer detection by using the methylation of these targets in voided urine samples is under-way. The tumor suppressive function of these methylated targets in bladder cancer deserves further investigation. Citation Format: Chia-Ming Yeh, Pi-Che Chen, Wen-Yu Huang, Cheng-Huang Shen, Cheng-Da Hsu, Michael Wy Chan. Identification of a novel hypermethylated tumor suppressor gene in human bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1359. doi:10.1158/1538-7445.AM2014-1359

Accuracy of urinary human papillomavirus testing for presence of cervical HPV: systematic review and meta-analysis

Objective To determine the accuracy of testing for human papillomavirus (HPV) DNA in urine in detecting cervical HPV in sexually active women.Design Systematic review and meta-analysis.Data sources Searches of electronic...

Urinalysis in children and adolescents.

Urinalysis is the most commonly performed biochemical test in infancy and early childhood. The urine sample should be correctly obtained, age-specific aspects should be considered, and age-dependent reference values should be used. This review is based on a selective literature search in electronic databases, textbooks, and guidelines from Germany and abroad on the acquisition of urine samples and the performance of urinalysis in infancy and early childhood. The timing and mode of acquisition of the urine sample affect the assessment of hematuria, proteinuria, leukocyturia, nitrituria, and the uropathogenic bacterial colony count in the urine culture. Dipstick tests can be used for targeted screening for these features. The test results should be interpreted together with the findings of urine microscopy, the medical history, and the physical examination. Proteinuria should be quantified and differentiated; both of these things can be done either from collected urine or (especially in infants and young children) from a spontaneously voided urine sample, by determination of the protein/creatinine quotient. Orthostatic proteinuria in an adolescent requires no further evaluation or treatment. Hematuria should be characterized as either glomerular or non-glomerular erythrocyturia. Asymptomatic, isolated microhematuria in childhood is not uncommon and often transient; in the absence of a family history, it usually does not require an extensive work-up. Proteinuria combined with hematuria should arouse the suspicion of glomerulonephritis. Urinalysis in infancy and early childhood is a simple and informative diagnostic test as long as the urine sample has been obtained properly and the results are interpreted appropriately for this age group.

Establishing reference intervals for bone turnover markers in healthy postmenopausal women in a nonfasting state.

In order to interpret bone turnover markers (BTMs), we need to establish healthy reference intervals. It is difficult to establish reference intervals for older women because they commonly suffer from diseases or take medications that affect bone turnover. The aims of this study were: (1) to identify diseases and drugs that have a substantial effect on BTMs; (2) to establish reference intervals for premenopausal and postmenopausal women; and (3) to examine the effects of other factors on BTMs in healthy postmenopausal women. We studied women aged 30-39 years (n=258) and women aged 55-79 years (n=2419) from a five-European centre population-based study. We obtained a nonfasting serum and second morning void urine samples at a single baseline visit. BTMs were measured using automated immunoassay analysers. BTMs were higher in patients with vitamin D deficiency and chronic kidney disease. Three or more BTMs were higher in women who were osteoporotic and at least two BTMs were lower in women who were oestrogen replete, taking osteoporosis treatments or having diseases known to affect bone turnover. These were used as exclusion criteria for selecting the populations for the reference intervals. The reference intervals for BTMs were higher in postmenopausal than premenopausal women. Levels of BTMs were not dependent on geographical location and increased with age.

Interleukin-6 concentrations in the urine and dipstick analyses were related to bacteriuria but not symptoms in the elderly: a cross sectional study of 421 nursing home residents.

BackgroundUp to half the residents of nursing homes for the elderly have asymptomatic bacteriuria (ABU), which should not be treated with antibiotics. A complementary test to discriminate between symptomatic urinary tract infections (UTI) and ABU is needed, as diagnostic uncertainty is likely to generate significant antibiotic overtreatment. Previous studies indicate that Interleukin-6 (IL-6) in the urine might be suitable as such a test. The aim of this study was to investigate the association between laboratory findings of bacteriuria, IL-6 in the urine, dipstick urinalysis and newly onset symptoms among residents of nursing homes.MethodsIn this cross sectional study, voided urine specimens for culture, urine dipstick and IL-6 analyses were collected from all residents capable of providing a voided urine sample, regardless of the presence of symptoms. Urine specimens and symptom forms were provided from 421 residents of 22 nursing homes. The following new or increased nonspecific symptoms occurring during the previous month were registered; fatigue, restlessness, confusion, aggressiveness, loss of appetite, frequent falls and not being herself/himself, as well as symptoms from the urinary tract; dysuria, urinary urgency and frequency.ResultsRecent onset of nonspecific symptoms was common among elderly residents of nursing homes (85/421). Urine cultures were positive in 32% (135/421), Escherichia coli was by far the most common bacterial finding. Residents without nonspecific symptoms had positive urine cultures as often as those with nonspecific symptoms with a duration of up to one month. Residents with positive urine cultures had higher concentrations of IL-6 in the urine (p < 0.001). However, among residents with positive urine cultures there were no differences in IL-6 concentrations or dipstick findings between those with or without nonspecific symptoms.ConclusionsNonspecific symptoms among elderly residents of nursing homes are unlikely to be caused by bacteria in the urine. This study could not establish any clinical value of using dipstick urinalysis or IL-6 in the urine to verify if bacteriuria was linked to nonspecific symptoms.

Unusually low prevalence of Mycoplasma genitalium in urine samples from infertile men and healthy controls: a prevalence study

ObjectiveTo detect Mycoplasma genitalium in urine samples of infertile men and men without any signs of infection in order to investigate whether M. genitalium and other genital mycoplasmas (Mycoplasma hominis...

The Risk of Urinary Tract Infection after Flexible Cystoscopy in Patients with Bladder Tumor Who Did Not Receive Prophylactic Antibiotics

The frequency of febrile urinary tract infection was determined after outpatient flexible cystoscopy in antibiotic naïve patients with bladder tumor. A total of 3,108 outpatient cystoscopies were performed in 1,110 patients with bladder tumor. Immediately before cystoscopy patients submitted a voided urine sample for culture. Significant bacteriuria was defined as greater than 10(4) cfu/ml of a single organism. Patients received no antibiotics immediately before or after cystoscopy. They were followed for 30 days for onset of febrile urinary tract infection. Of the 3,108 patient cystoscopies 673 (22%) had asymptomatic bacteriuria and 2,435 (78%) had sterile urine. A febrile urinary tract infection developed within 30 days of cystoscopy in 59 patients (1.9%), including in 3.7% of infected and 1.4% of uninfected patients (p = 0.01). All cases resolved within 12 to 24 hours with oral antibiotics. No patient was hospitalized for bacterial sepsis. Antibacterial therapy before outpatient flexible cystoscopy does not appear necessary in patients who have no clinical signs or symptoms of acute urinary tract infection, including bacteriuria.

The value of the NMP22 test for superficial bladder cancer diagnosis and follow-up.

In this study, we investigated the efficacy of nuclear matrix protein 22 (NMP22) in the diagnosis and surveillance of bladder cancer. Patients with hematuria or who applied for cystoscopic control of proven bladder cancer were prospectively enrolled in this study. Routine cytologic examination and NMP22 test were performed on the voided urine sample obtained before the cystoscopy. The patients who had been diagnosed with bladder cancer were categorized according to stage, grade, number, size of the tumor and risk of the disease. Then the diagnostic performance of the NMP22 and the cytology test, alone or in combination, were evaluated separately using ROC curves in the diagnosis and surveillance groups. A total of 87 patients (87/136) were investigated because of hematuria. The sensitivity, specificity, positive and, negative predictive values, and positive likelihood ratio (LR+) of the NMP22 test were 70, 80, 68, 81, and 3.42%, respectively. While, the sensitivity, specificity, positive and, negative predictive values, and positive likelihood ratio (LR+) of the cytology examination were 27, 96, 82, 68, and 7.36%, respectively. There were 49 patients in the bladder cancer group. The sensitivity, specificity, positive, and negative predictive values and positive likelihood ratio (LR+) of the NMP22 test in these patients were 33, 76, 31, 78 and 1.37%, respectively. The sensitivity, specificity, positive and, negative predictive values, and positive likelihood ratio (LR+) of the cytology examination were 25%, 97%, 75%, 80% and 9.25, respectively. NMP22 test can be used as an adjunctive tool for the detection of bladder cancer, but its diagnostic performance is limited in surveillance when used alone or in combination with a cytology examination.

SAT0486 Reference Intervals for Bone Turnover Markers in Spanish Premenopausal Women

BackgroundBone turnover markers (BTMs) are used in clinical practice for assessing patients with osteoporosis and their treatment. In Spain it is necessary to fine-tune the reference intervals, since they were...

Children’s personal exposure to PM10 and associated metals in urban, rural and mining activity areas

There has been limited study of children’s personal exposure to PM10 and associated metals in rural and iron ore mining activity areas where PM10 concentrations can be very high. We undertook a small study of 70 children where 13 children were recruited in an area of iron ore mining processing and shipping, 15 children from an area in the same region with no mining activities, and 42 children in an urban area. Each child provided a 24h personal exposure PM10 sample, a first morning void urine sample, a hair sample, time activity diary, and self administered questionnaire. Children’s 24h personal PM10 concentrations were low (median of 28μgm−3 in the mining area; 48μgm−3 in the rural area and 45μgm−3 in the urban area) with corresponding outdoor PM10 concentrations also low. Some very high personal PM10 concentrations were recorded for individuals (>300μgm−3) with the highest concentrations recorded in the mining and rural areas in the dry season. PM10 concentrations were highly variable. Hair aluminium, cadmium and manganese concentrations were higher in the iron ore activity area, while hair mercury, copper and nickel concentrations were higher in the urban area. Factors such as season and ventilation appear to be important but this study lacked power to confirm this. These results need to be confirmed by a larger study and the potential for absorption of the metals needs to be established along with the factors that increase exposures and the potential for health risks arising from exposure.

Discordant prevalence of Chlamydia trachomatis in asymptomatic couples screened by two screening approaches

This study was carried out to observe the effect of screening both members of an asymptomatic couple for Chlamydia trachomatis. First void urine samples were collected from 105 women and their male sex partners. Women were recruited for screening at a sexual health clinical setting (age 16-25 years), and home sampling screening options were used for men. Using PCR we detected seven positive C. trachomatis samples in women (6.6%) and five in men (4.6%). The concordant infection rate was 33% (3/9 couples). Routine urine screening of the female partner might result in substantial underestimation of the C. trachomatis prevalence within the couple, where perhaps 56% of the couples where at least one partner tested positive would remain undiagnosed. Screening both partners compared with women- or men-only screening increased the detection rate of positive couples. Furthermore, the use of alternative screening approaches in different clinical settings increases testing in at risk populations.

1104 FGFR3 mutation analysis in voided urine samples to decrease cystoscopies and cost in nonmuscle invasive bladder cancer surveillance: A comparison of 3 strategies

1104 FGFR3 mutation analysis in voided urine samples to decrease cystoscopies and cost in nonmuscle invasive bladder cancer surveillance: A comparison of 3 strategies

Seasonal perspective of dietary arsenic consumption and urine arsenic in an endemic population

Exposure to arsenic in arsenic endemic areas is most remarkable environmental health challenges. Although effects of arsenic contamination are well established, reports are unavailable on probable seasonal variation due to changes of food habit depending on winter and summer seasons, especially for endemic regions of Nadia district, West Bengal. Complete 24-h diets, drinking-cooking water, first morning voided urine samples, and diet history were analyzed on 25 volunteers in arsenic endemic Chakdah block of Nadia district, once in summer followed by once in winter from the same participants. Results depicted no seasonal variation of body weight and body mass index. Arsenic concentration of source drinking and cooking water decreased (p = 0.04) from 26μgL(-1) in summer to 6μgL(-1) in winter season. We recorded a seasonal decrease of water intake in male (3.8 and 2.5Lday (-1)) and female (2.6 and 1.2Lday(-1)) participants from summer to winter. Arsenic intake through drinking water decreased (p = 0.04) in winter (29μgday(-1)) than in summer (100μgday(-1)), and urinary arsenic concentration decreased (p = 0.018) in winter (41μgL(-1)) than in summer (69μgL(-1)). Dietary arsenic intake remained unchanged (p = 0.24) over the seasons. Hence, we can infer that human health risk assessment from arsenic needs an insight over temporal scale.

To evaluate the diagnostic value of protein: creatinine ratio in a single voided urine sample for quantitation of proteinuria compared to those of a 24-hour urine sample in patients with preeclampsia

Objective: This study was done to evaluate the diagnostic value of protein: creatinine ratio in a single voided urine sample for quantitation of proteinuria compared to those of a 24 hour urine sample in patients with preeclampsia. Methods: A prospective simple random sample study was done on the hypertensive pregnant women attending the antenatal clinic or admitted in Department of Obstetrics and Gynaecology. It included all women being evaluated for preeclampsia, regardless of the alerting sign or symptom, suspected severity or co-morbid conditions. The main measures were the urinary protein to urinary creatinine ratio by random (spot) direct measurement and the 24-h urinary protein excretion by a 24-h urine collection. The data obtained was statistically analyzed. Results: Out of the 78 patients with gestational hypertension included in our study 48 patients had significant proteinuria (e”300mg/day). Only 2 patients had proteinuria of the range of greater than 3500mg. Among the patients, 50 had a positive protein: creatinine ratio (e”0.3) while 28 patients had a negative protein: creatinine ratio (&lt;0.3). The P: C ratio was able to correctly identify 44 out of 48 patients with significant proteinuria (when the comparison is made with the gold-standard test; i.e., 24-hour urine protein). It could also identify 24 out of 30 patients without significant proteinuria as compared to the gold-standard test. In this study, the Protein: Creatinine ratio with a sensitivity of 91.67%, a specificity of 80%, positive predictive values 88% and the negative predictive values 85.71%. Conclusions: Our data suggests that the protein: creatinine ratio in single voided urine is a highly accurate test (p value &lt; 0.0000001) for discriminating between insignificant and significant proteinuria. Based on the above findings we conclude that a random urine protein excretion predicts the amount of 24- hour urine protein excretion with high accuracy. This could be a reasonable alternative to the 24-hour urine collection for detection of significant proteinuria in hospitalised pregnant women with suspected preeclampsia. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-2, 45-53 DOI: http://dx.doi.org/10.3126/jcmsn.v9i2.9687

Microfilariae of Wuchereria Bancrofti in a Patient of Chylous Haematuria: Report of an Unusual Finding in Urine Cytology

Filariasis is a disabling parasitic disease and it constitutes as a major health problem in most of the tropical and sub-tropical countries. One hundred and twenty million people in at least 80 tropical and sub-tropical countries are infected with lymphatic filarial parasite, with one billion people being at risk of the disease. The laboratory diagnosis of filariasis is conventionally made by demonstrating microfilaria in peripheral blood smear. However, microfilaria have been incidentally detected by doing fine needle aspiration of various lesions in clinically unsuspected cases of filariasis. In 1982, detected microfilariae in the sediment smears of cystoscopically catheterized urine samples, but reports on detection of microfilaria in normally voided urine samples are extremely rare. Here, we are reporting, such a case of microfilariae of Wuchereria bancrofti in an 18-year-old boy who presented with chylous haematuria.

Circadian dysrhythm and advanced prostate cancer.

199 Background: The circadian rhythm regulates diverse biologic pathways including tumor oncogenes, metabolism, and cell proliferation. Dysregulation of the circadian rhythm arises from faulty input signals such as exposure to light at night, variability in core circadian rhythm genes, and variation in outputs that regulate circadian behavior including melatonin. There is compelling biologic rationale, but little human data, on circadian dysrhythm and advanced prostate cancer. Methods: We undertook an integrative molecular epidemiology study of circadian dysrhythm and advanced prostate cancer among men in the Icelandic AGES-Reykjavik cohort and the U.S. Health Professionals Follow-up Study, which allowed integration of questionnaire data, biorepositories, and long-term follow-up. We characterized circadian dysrhythm using complimentary approaches: information on sleep problems from questionnaires, prediagnostic melatonin (6-sulfatoxymelatonin) measured on first morning void urine samples, and genetic variation across twelve circadian clock genes. We used multivariable regression models to estimate relative risks (RR) and 95% confidence intervals (CI) of associations with advanced prostate cancer, adjusted for potential confounders. Results: Twenty percent of men reported sleep problems. Men who had trouble falling asleep (RR = 2.1; 95% CI 0.7-6.2) and staying asleep (RR=3.2, 95% CI 1.1-9.7) had an increased risk of developing advanced prostate cancer. Men with sleep problems had significantly lower melatonin levels compared to those without. Low melatonin levels were associated with a statistically significant 4-fold higher risk of advanced prostate cancer compared to those with high levels (95% CI: 1.25-10.0). Variant alleles in two SNPs in cryptochrome (CRY1), involved in generating and maintaining circadian rhythms, were significantly associated with risk of advanced prostate cancer in both cohorts, with a gene-level p-value&lt;0.01. Conclusions: Our results suggest there are multiple nodes in the circadian rhythm that are associated with an increased risk of advanced prostate cancer. As such, there is the potential for complimentary strategies to target circadian disruption and reduce the risk of advanced prostate cancer.

Evaluation of urinary HURP mRNA as a marker for detection of bladder cancer: relation to bilharziasis

This study was carried out to assess the efficacy of urinary hepatoma up-regulated protein (HURP) RNA in bladder cancer diagnosis and its relation to bilharziasis. Voided urine samples and blood were collected from 344 consecutive participants: 211 patients diagnosed with bladder cancer, 71 patients with benign urological disorders and 62 healthy volunteers. Serologic assessment of schistosomiasis antibody in sera, urine cytology and estimation of HURP RNA by reverse transcription polymerase chain reaction in urothelial cells was carried out in all samples. HURP RNA expression showed a significant difference among the three investigated groups. The best cutoff point for HURP RNA was determined as 0.0132 at 78.67% sensitivity and 94% specificity. The sensitivity of urine cytology was improved when combined with HURP RNA in detection of early stage (77.3%), low grade (85.3%) and bilharzial bladder cancer (78.1%). Detection of urinary HURP RNA is a useful non-invasive test for early detection of bladder cancer and bilharzial bladder cancer and it improves sensitivity of urine cytology up to 91%.

The clinical relevance of urinary soluble fas (sFas) for diagnosis of bilharzial bladder cancer

Background: Fas/CD95, a membrane-bound type I protein, plays a key role in induction of apoptosis and intumorigenesis. Objective: We adapted and evaluated measurement of urinary sFas using enzyme-linked immunosorbent assayand compared the results with voided urine cytology. Materials and Methods: Voided urine samples were provided from 203 individuals (120 bladder cancer [112bilharzial]; 43 benign urologic disorders [20 bilharzial dysplastic lesions]; and 40 healthy volunteers). Urinesediment was used for cytology and the supernatant for estimation of sFas by ELISA. Results: A receiver operating characteristic curve (ROC) was used to determine the best cutoff value for urinarysFas. Positivity rates and mean rank levels for sFas showed significant difference among the three investigatedgroups (p Conclusion: Urinary sFas may be used as a novel noninvasive diagnostic marker for bilharzial bladder cancerpatients. Further multicentric studies are warranted to corroborate these findings and to establish an optimalsFas cut-point. Keywords: Bilharzial bladder cancer, sFas, voided urine cytology

Urinary phthalate metabolites among elementary school children of Korea: Sources, risks, and their association with oxidative stress marker

Phthalates have been used in a variety of consumer products and hence frequently been detected in humans. Children are susceptible to endocrine disrupting chemicals such as phthalates, but only limited information is available on the sources of exposure and potential adverse health effects among children. In this study, elementary school students (n=39, aged 9–12years) were recruited in Seoul, and first void urine samples were collected twice in three-day intervals. Then six phthalate metabolites were analyzed by high performance liquid chromatography with triple quadrupole tandem mass spectrometry. In addition, malondialdehyde (MDA) as an oxidative stress marker was measured. A questionnaire was conducted and information on food consumption and the use of plastic packaging or storage materials was gathered. The concentrations of phthalate metabolites varied substantially by sampling time even within the same subject, but all target metabolites were detected in 100% of the samples with the highest geometric mean of 107μg/g-creatinine for mono-n-butyl phthalate (MnBP). Urinary levels of mono-isobutyl phthalate (MiBP), and MnBP among Korean children were 8 and 3 times greater than those reported for US children, but those of monoethyl phthalate (MEP) were about 5 times lower than those of US children. Estimated phthalate intakes were generally in safe range, but in 3–8% of the participating children, the hazard quotients greater than one were noted. Urinary MDA concentrations were significantly associated with several metabolite levels after adjusting covariates in regression model. Consumption of dairy products or meat, and use of a plastic material were significantly associated with the DEHP metabolites or MnBP levels in multivariate model. The results of this study provide evidence of the association between phthalate exposure and oxidative stress especially among the early teenagers, and identified major sources that can be applied to development of management plan for phthalate exposure among children.