A prospective observational study of urinary cytokines and inflammatory response in patients with Overactive Bladder Syndrome.

BACKGROUND: Contemporary studies have discredited the methods used to exclude urinary tract infection (UTI) when treating overactive bladder (OAB). Thus we must revisit the OAB phenotype to check that UTI has not been overlooked. AIMS: To examine the differences in urinary cytokines IL6 and lactoferrin in OAB patients compared to controls, with references to microscopy of urine and enhanced quantitative urine culture. METHODS: A blinded, prospective cohort study with normal controls using six repeated measures, achieved two-monthly, over 12 months. RESULTS: The differences between patients and controls in urine IL6 (F = 49.0, p < .001) and lactoferrin (F = 228.5, p < .001) were significant and of a magnitude to have clinical implications. These differences were for lactoferrin correlated to symptoms (9.3, p = .003); for both to pyuria (IL6 F = 66.2, p < .001, Lactoferrin F = 73.9, p < .001); and for IL6 microbial abundance (F = 5.1, p = .024). The pathological markers had been missed by urinary dipsticks and routine MSU culture. CONCLUSION: The OAB phenotype may encompass patients with UTI that is being overlooked because of the failure of standard screening methods.

Urine Lactoferrin as a Potential Biomarker Reflecting the Degree of Malignancy in Urothelial Carcinoma of the Bladder.

Urothelial carcinoma of the bladder (UCB) is potentially life-threatening; therefore, we aimed to discover a novel urine biomarker for diagnosis and prognostication of UCB. This is a retrospective case-control study. Exploration of a new biomarker using urine from 20 UCB patients in the present study revealed that urinary level of lactoferrin (LF), a multifunctional glycoprotein released from neutrophils, was higher in 11 of 15 with invasive/high-grade UCB than 5 with non-invasive one, and 2 healthy adults. We therefore focused on LF and assessed the value of urine LF normalized by urine creatinine concentration (LF/Cr) using an enzyme-linked immunosorbent assay. Diagnostic performance of urine LF/Cr was examined using urine from 92 patients with primary (newly diagnosed) untreated UCB and 166 controls without UCB, including 62 patients with pyuria, and 104 subjects without pyuria consisting of 84 patients and 20 healthy adults. However, the diagnostic accuracies were accompanied by the risk of bias. In 92 primary UCB patients, both pyuria and tumor-infiltrating neutrophils (TINs) were independent predictors for urine LF/Cr. In contrast, TINs or urine LF/Cr were independent predictors for invasive histology, whereas pyuria was not. In terms of prognostication, urine LF/Cr and nodal metastasis were independent predictors of disease-specific survival in 22 patients with muscle-invasive bladder cancer, characterized by a high mortality rate, in the Cox proportional hazards model. In conclusion, urine LF/Cr linked to TINs was a predictor of both invasive histology and prognosis in UCB. Urine LF/Cr is a potential biomarker reflecting the degree of malignancy in UCB.

Iron-related proteins: candidate urine biomarkers in childhood HIV-associated renal diseases.

BACKGROUND: Because of the risk of performing renal biopsies in children with co-morbid conditions, we carried out this study to identify candidate protein biomarkers in the urine of HIV-infected children with renal disease. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Urine samples from HIV-infected children with biopsy proven HIV-nephropathy (HIVAN; n = 4), HIV-associated Hemolytic Uremic Syndrome (HIV-HUS; n = 2), or no renal disease (n = 3) were analyzed by two-dimensional electrophoresis (2-DE) and proteomic methods. Positive findings were confirmed in HIV-infected children with (n = 20) and without (n = 10) proteinuria using commercially available assays. RESULTS: By 2-DE analysis, a single urine marker was not sufficient to distinguish children with HIVAN from the others. High urine levels of beta(2)-microglobulin and retinol-binding protein (RBP) suggested the presence of tubular injury. In addition, we found elevated urine levels of iron and the iron-related proteins, transferrin, hemopexin, haptoglobin, lactoferrin, and neutrophil gelatinase-associated lipocalin (NGAL), in children with HIVAN and HIV-HUS. Furthermore, we detected a significant accumulation of iron in the urine and kidneys of HIV-transgenic (Tg) rats with renal disease. CONCLUSION: These findings suggest that iron and iron-related proteins might be promising candidate urine biomarkers to identify HIV-infected children at risk of developing HIVAN and HIV-HUS. Moreover, based on the results of previous studies, we speculate that the release or accumulation of iron in the kidney of HIV-infected children may contribute to the rapid progression of their renal disease, and could become a new therapeutic target against HIVAN and HIV-HUS.

Sexual function after bilateral retroperitoneal lymph node dissection for nonseminomatous testicular cancer.

This study concerns the sexual functions of 101 patients who had undergone bilateral retroperitoneal lymph node dissection for stage I or II nonseminomatous testicular cancer between 1969 and 1982. All patients were without evidence of disease after at least 4 years of follow-up. Antegrade ejaculation was present in 12 patients, while 89 patients experienced "dry ejaculation." Urine collected after intercourse or masturbation from 75 patients with dry ejaculation showed retrograde ejaculation in 55 and lack of ejaculatory emission into the urethra in 20 patients. Regarding other sexual functions, 17 patients had a diminished sexual desire (especially those patients who had received radiotherapy), 12 experienced difficulty reaching organism, and 6 complained of erectile dysfunction. The incidence of a contralateral hydrocele developing after retroperitoneal lymph node dissection seems to correlate with ligation of the contralateral spermatic vessels and their lymphatics. A review of the literature is presented comparing the types of dissection with the incidence of sexual disorders after retroperitoneal lymph node dissection. Since preserving normal ejaculation and fertility is important, a modified or unilateral retroperitoneal lymph node dissection, when required, is advocated. In patients, with stage I disease the therapy may be limited to an orchiectomy without lymph node dissection. In patients with retroperitoneal lymph node metastases combination chemotherapy with cisplatin and tumor excision gives good results. Patients with true retrograde ejaculation can be treated with alpha-sympathomimetic drugs such as imipramine HCl, and thus be offered the chance of fatherhood by coitus.