Comparison of miniaturized percutaneous nephrolithotomy and flexible ureterorenoscopy for the management of 10-20 mm renal stones in obese patients.

PURPOSE: To evaluate and compare effectivity and safety of flexible ureteroscopy (F-URS) and mini-percutaneous nephrolithotomy (mPNL) for 10-20 mm renal stones in obese patients. METHODS: Between 2012 and 2015, charts of patients who were treated with F-URS or mPNL for 10-20 mm kidney stone(s) were analyzed. Patients with BMI > 30 kg/m(2) were enrolled into the study. Total of 315 patients were treated with mPNL, and 56 patients were matched our inclusion criteria. In the same period, F-URS was performed in 669 patients, and 157 of them had 10-20 mm kidney stones, and their BMI values were >30 kg/m(2). The patients were retrospectively matched at a 1:1 ratio to index F-URS-mPNL cases with respect to the patient age, gender, ASA score, BMI and size, number, and location of stone. RESULTS: Gender, age, BMI, stone size, stone number, location of stone(s), and ASA scores were similar between groups. The mean operation time was significantly longer in mPNL group (p: 0.021). However, the mean fluoroscopy time was similar (p: 0.270). Hemoglobin drop requiring blood transfusion and angioembolization was performed in two and one patients after mPNL, respectively. Overall complication rate was significantly higher in mPNL group than F-URS group (30.3 vs. 5.3 %, p: 0.001). CONCLUSION: Our results demonstrated that both F-URS and mPNL achieve acceptable stone-free rates in obese patients with 10-20 mm renal stones. However, complication rates were significantly lower in F-URS group.

A Modified Antegrade Stenting Technique for Laparoscopic Pyeloplasty in Infants and Children.

OBJECTIVE: There are 2 critical steps of stent placement during laparoscopic pyeloplasty (LP) in children. Introduction to the ureteropelvic junction and passing through the ureterovesical junction. We aimed at overcoming those 2 steps by creating a modified technique. METHODS: Consecutive 27 children undergoing transperitoneal laparoscopic dismembered pyeloplasty by a single surgeon were prospectively enrolled into this study. The modifications of our technique are using an Amplatz dilator and a closed tip stent. RESULTS: The mean age of the children was 6.7 (range 4 months-17 years). The mean time of stent insertion was 2.7 ± 2.0 (2-6) min and the operative time was 128.3 ± 17.6 (90-180) min. The mean number of days of hospital stay was 2.0 ± 0.4 (1-3). After a mean follow-up period of 20.3 ± 4.2 (14-30) months, no operative failure was detected. CONCLUSION: Our modified technique is a completion of the current armamentarium for stent placement during LP in infants and children.

Comparison of flexible ureterorenoscopy and micropercutaneous nephrolithotomy in the treatment for moderately size lower-pole stones.

PURPOSE: To present a retrospective comparative clinical study of micropercutaneous nephrolithotomy (microperc) versus flexible ureterorenoscopy (F-URS) in treatment of moderate-size lower-pole stones (LPSs). METHODS: We retrospectively reviewed data on patients with isolated LPSs ≤2 cm in diameter treated with F-URS and/or microperc in two referral centers. Patients were divided into two groups by treatment modality: F-URS (Group 1) and microperc (Group 2). Demographics and perioperative parameters were analyzed. RESULTS: A total of 127 patients with isolated LPSs were treated via F-URS (Group 1, n = 59) and microperc (Group 2, n = 68). Mean patient age in microperc group was slightly lower than in F-URS group (p = 0.112). We found no statistically significant difference in terms of either the size or number of stones in two groups (p = 0.113 and p = 0.209, respectively). Operative time was shorter in microperc, whereas fluoroscopy time was shorter in F-URS (60.1 ± 26.2 vs. 46.2 ± 24.3 min, p < 0.001; and 28.3 ± 19.1 vs. 108.9 ± 65.2 s, p < 0.001). Mean fall in hemoglobin level was statistically significantly lower in F-URS and hospitalization time was also significantly shorter in F-URS (0.68 ± 0.51 vs. 1.29 ± 0.88 mg/dL, p < 0.001; and 23.0 ± 58.1 vs. 33.8 ± 17.2 h, p < 0.001, respectively). Stone-free rates (SFRs) were 74.5 % (44/59) in Group 1 and 88.2 % (60/68) in Group 2 (p < 0.001). CONCLUSIONS: We found that microperc was safe and efficacious when used to treat moderate-size LPSs and may be considered as an alternative to F-URS, affording a higher SFR. Our study supports the notion that microperc should play an increasing role in treatment of LPSs.

Categorization of intraoperative ureteroscopy complications using modified Satava classification system.

OBJECTIVES: To review our experience with ureteroscopy (URS) in the treatment of ureteral calculi and stratify intraoperative complications of URS according to the modified Satava classification system. PATIENTS AND METHODS: We performed a retrospective analysis of 1,208 patients (672 males and 536 females), with a mean age of 43.1 years (range 1-78), who underwent ureteroscopic procedures for removal of ureteral stones. Intraoperative complications were recorded according to modified Satava classification system. Grade 1 complications included incidents without consequences for the patient; grade 2 complications, which are treated intraoperatively with endoscopic surgery (grade 2a) or required endoscopic re-treatment (grade 2b); and grade 3 complications included incidents requiring open or laparoscopic surgery. RESULTS: The stones were completely removed in 1,067 (88.3%) patients after primary procedure by either simple extraction or after fragmentation. The overall incidence of intraoperative complications was 12.6%. The most common complications were proximal stone migration (3.9%), mucosal injury (2.8%), bleeding (1.9%), inability to reach stone (1.8%), malfunctioning or breakage of instruments (0.8%), ureteral perforation (0.8%) and ureteral avulsion (0.16%). According to modified Satava classification system, there were 4.5% grade 1; 4.4% grade 2a; 3.2% grade 2b; and 0.57% grade 3 complications. CONCLUSION: We think that modified Satava classification is a quick and simple system for describing the severity of intraoperative URS complications and this grading system will facilitate a better comparison for the surgical outcomes obtained from different centers.

Cancer detection rates of different prostate biopsy regimens in patients with renal failure.

We aimed to evaluate the cancer detection rates of 6-, 10-, 12-core biopsy regimens and the optimal biopsy protocol for prostate cancer diagnosis in patients with renal failure. A total of 122 consecutive patients with renal failure underwent biopsy with age-specific prostate-specific antigen (PSA) levels up to 20 ng/mL. The 12-core biopsy technique (sextant biopsy + lateral base, lateral mid-zone, lateral apex, bilaterally) performed to all patients. Pathology results were examined separately for each sextant, 10-core that exclude parasagittal mid-zones from 12-cores (10a), 10-core that exclude apex zones from 12-cores (10b) and 12-core biopsy regimens. Of 122 patients, 37 (30.3%) were positive for prostate cancer. The cancer detection rates for sextant, 10a, 10b and 12 cores were 17.2%, 29%, 23.7% and 30.7%, respectively. Biopsy techniques of 10a, 10b and 12 cores increased the cancer detection rates by 40%, 27.5% and 43.2% among the sextant technique, respectively. Biopsy techniques of 10a and 12 cores increased the cancer detection rates by 17.1% and 21.6% among 10b biopsy technique, respectively. There were no statistical differences between 12 core and 10a core about cancer detection rate. Adding lateral cores to sextant biopsy improves the cancer detection rates. In our study, 12-core biopsy technique increases the cancer detection rate by 5.4% among 10a core but that was not statistically different. On the other hand, 12-core biopsy technique includes all biopsy regimens. We therefore suggest 12-core biopsy or minimum 10-core strategy incorporating six peripheral biopsies with elevated age- specific PSA levels up to 20 ng/mL in patients with renal failure.

Parenchymal thickness: does it have an impact on outcomes of percutaneous nephrolithotomy?

OBJECTIVE: To evaluate whether renal parenchymal thickness (RPT) has an effect on the outcomes of percutaneous nephrolithotomy (PNL). METHODS: We performed a retrospective analysis of 144 patients with lower pole and/or renal pelvic stones who underwent PNL. The relationship between RPT and peri- and postoperative measures was evaluated. RESULTS: The average age was 45.94 ± 14.47 (15-76) years. The mean BMI was calculated as 27.47 ± 4.73 (16.9-44.9) kg/m(2). The mean stone burden was 293 ± 126 (150-800 mm(2)). The mean RPT was measured as 17.33 ± 5.32 (6-35) mm. No correlation was detected between the RPT and the operation or fluoroscopy times or the duration of hospitalization (p = 0.63, 0.52, 0.08, respectively). The mean drop in hemoglobin level was 1.45 ± 1.25 (0-9) g/dl. A negative correlation was detected between hemoglobin drop and RPT (p = 0.01, r = -0.23). However, the RPT was similar in patients who did or did not require a blood transfusion (p = 0.09). The RPT was found to have no impact on success rate (p = 0.4). CONCLUSION: The postoperative hemoglobin drop increases in parallel with the increase in RPT. However, no relationship was detected between the RPT and blood transfusion, overall success rate or any other perioperative parameters.

Is the percutaneous nephrolithotomy procedure complicated in patients with anterior caliceal stones?

OBJECTIVES: It was the aim of this study to evaluate and compare the outcomes of percutaneous nephrolithotomy (PNL) for the treatment of posterior and anterior caliceal stones. PATIENTS AND METHODS: We performed a retrospective analysis of 86 patients with isolated caliceal stones who underwent PNL between 2011 and 2012. The patients were classified into two groups according to the localization of the stone, either in the anterior (group 1, n = 41) or posterior (group 2, n = 45) calyx, on axial plane computed tomography. RESULTS: The mean age, male/female ratio and stone size and location were similar in both groups. Fluoroscopy, operation time and duration of hospitalization were also similar between groups. Patients in group 1 had a greater postoperative hemoglobin drop than patients in group 2. Blood transfusion was required for 5 patients in group 1 and for 4 patients in group 2. In addition, open conversion was required for 2 patients in group 1 during the early postoperative period because of extensive bleeding. Hemodynamics were stabilized with angioembolization in 2 patients with prolonged hematuria in group 1. The overall success and complication rates were similar in both groups. CONCLUSION: Although the postoperative hemoglobin drop did not significantly differ between groups, hemorrhaging was more severe in patients with anterior caliceal stones than in those with posterior caliceal stones.

The effect of micronized purified flavonoid fraction on the prevention of testicular pathologies in adolescent rats with experimentally induced varicocele.

PURPOSE: We investigated the effect of micronized purified flavonoid fraction on the prevention of testicular pathologies following varicocele induction. MATERIALS AND METHODS: A total of 66 adolescent (6-week-old) male Wistar rats were included in study. Rats were divided into 7 groups, including group 1--control, group 2--sham operation, group 3--left varicocele induced, group 4--varicocele induced, varicocelectomy done 4 weeks later and micronized purified flavonoid fraction administered for 4 weeks, group 5--varicocele induced and micronized purified flavonoid fraction administered for 8 weeks, group 6--varicocele induced and beginning 4 weeks later micronized purified flavonoid fraction administered for 4 weeks, and group 7--varicocele induced and varicocelectomy done 4 weeks later. Before sacrifice bilateral real-time testicular microvascular perfusion of all rats was measured using the PeriFlux System 5000 PF 5010 LDPM Unit (Perimed, Järfälla, Sweden). All testes were graded according to the Johnsen scoring system. To assess apoptosis caspase-3 levels were measured. RESULTS: Testicular weight in group 3 was markedly decreased and the extent of seminiferous tubular damage was significantly increased compared with the other groups. Bilateral testicular blood flow and the number of apoptotic germ cells were greater in group 3. Significantly higher Johnsen scores and a meaningful decrease in the apoptotic index were detected in groups 4 to 7 compared with group 3. CONCLUSIONS: We observed favorable effects of micronized purified flavonoid fraction on the regression of testicular damage secondary to varicocele.

"Snodgraft" technique for the treatment of primary distal hypospadias: pushing the envelope.

PURPOSE: "Snodgraft" modification has been proposed to reduce the risk of meatal/neourethral stenosis in distal hypospadias. We applied the Snodgraft technique by using inner preputial graft in primary distal hypospadias repair. MATERIALS AND METHODS: A total of 102 consecutive patients undergoing the Snodgraft procedure were prospectively studied between 2006 and 2011. Mean patient age was 7.2 years. Localization of the meatus was glanular in 5 patients, coronal in 49, subcoronal in 45 and mid penile in 3. In all patients the posterior urethral plate was incised, and the graft harvested from the inner prepuce was sutured from the old meatus to the tip of the glans. A neourethra was created over a urethral catheter using 6-zero polyglactin suture. An interpositional flap was laid over the urethra as a second barrier. All patients were followed at 3 to 6-month intervals for cosmetic and functional results. RESULTS: At a mean of 2.4 years of followup no patient had meatal stenosis or diverticulum at the inlay graft site. However, urethrocutaneous fistula was observed in 10 patients (9.8%). A slit-like appearance of neomeatus was achieved in all patients. During followup no obstructive urinary flow pattern was detected, and early and long-term maximum urine flow rates were comparable. CONCLUSIONS: No meatal/neourethral stenosis was observed in any patient undergoing a Snodgraft procedure. A randomized trial will be needed to prove that the incidence of meatal/neourethral stenosis is lower after Snodgraft repair compared to routine tubularized incised plate repair.

The effect of cadmium toxicity on renal nitric oxide synthase isoenzymes.

The aim of this study was to assess the cadmium (Cd) toxicity on renal nitric oxide synthase (NOS) isoenzymes. The study was carried out on 18 inbred male (Cd group: 10 and control group: 8) Wistar rats. Cd group received drinking water containing 15 mg/L Cd for 30 days; and at the end of the 30 days, plasma Cd was analysed. One kidney was snap frozen to assess the endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS) expressions by Western blot analyses, and the other kidney was preserved for histopathological examination. Plasma Cd levels were significantly elevated in the Cd group. The Western blot analyses found higher levels of eNOS, iNOS and nNOS in the Cd group but only eNOS and nNOS levels were statistically significant. There was no difference in pathological assessment of the renal tissues. Cd toxicity increases NOS isoenzyme levels and may affect renal physiology.

Lisinopril attenuates renal oxidative injury in L-NAME-induced hypertensive rats.

Hypertension and related oxidative stress are involved in the pathogenesis of any renal diseases. Angiotensin-converting enzyme inhibitors have multi-directional renoprotective effects. In this study, we aimed to investigate whether lisinopril treatment has any biochemical alterations on renal tissue in L-NAME (Nε-nitro-L-arginine methyl ester) induced hypertension model. Twenty-eight Sprague-Dawley rats were included in this study and divided into four equal groups (n = 7): control group, L-NAME treated group (75 mg/kg/day), L-NAME plus lisinopril treated group and only lisinopril treated group (10 mg/kg/day). L-NAME and lisinopril were continued for 6 weeks. Systolic blood pressures were measured by using tail cuff method. In biochemical analysis, malondialdehyde (MDA, an index of lipid peroxidation) levels, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in renal tissues were used as markers of oxidative stress-induced renal impairment. Microalbumin and N-acetyl-ß-D-glucosaminidase (NAG) in urine were determined as markers of renal tubular damage related to hypertension. Chronic L-NAME administration resulted in a significant depletion of serum nitric oxide (NO). When compared with control group, serum creatinine, microalbumin, urine NAG, renal tissue MDA level, and CAT activities were significantly high, while renal tissue SOD and GSH-Px activities low in L-NAME group. In the L-NAME plus lisinopril treated group, serum creatinine, microalbumin and urine NAG, renal MDA level and CAT activity decreased, whereas SOD, GSH-Px activities in renal tissue and serum NO levels were increased. Thus, lisinopril treatment reversed these effects. There were not any significant difference between L-NAME plus lisinopril treated group and control group concerning serum creatinine, renal tissue MDA level and SOD, GSH-Px, CAT activities. These results suggest that lisinopril could diminish biochemical alterations in L: -NAME induced hypertensive renal damage that occurs by oxidative stress.

Dietary vitamin C and E modulates oxidative stress induced-kidney and lens injury in diabetic aged male rats through modulating glucose homeostasis and antioxidant systems.

Diabetes induces oxidative stress in aged human and rat, although daily supplementation of vitamins C and E (VCE) can be beneficial to aged diabetic rats by reducing free radical production. The aim of the present study was to evaluate whether dietary VCE supplementation relieves oxidative stress in streptozotocin (STZ)-induced diabetic in aged rats. Thirty aged rats were randomly divided into three groups. The first group was used as a control. The second group was made diabetic using a single dose of intraperitoneal STZ. VCE-supplemented feed was given to aged diabetic rats constituting the third group. On the 21st day of the experiment, blood, lens and kidney samples were taken from all animals. Glutathione peroxidase (GSH-Px) activity in lens and kidney, reduced glutathione (GSH), vitamin E and ß-carotene concentrations in kidney were lower in the diabetic group than in the control whereas plasma glucose, urea and creatinine, and kidney and lens peroxidation (LP) levels were higher in the diabetic group than in the control. However, kidney and lens LP levels, and plasma glucose, urea and creatinine values were decreased by VCE supplementation. Lens and kidney GSH-Px activity, kidney GSH, vitamin E and ß-carotene concentrations and erythrocyte counts were increased by VCE treatment. Kidney weights, vitamin A, haemoglobin, hematocrit, leukocyte and platelets values were not changed by diabetes and/or VCE supplementation. VCE ameliorated also diabetes-induced histopathological changes in kidney. In conclusion, we observed that VCE supplementation is beneficial towards kidney and lens of aged diabetic rats by modulating oxidative and antioxidant systems.

The role of diffusion-weighted MRI and contrast-enhanced MRI for differentiation between solid renal masses and renal cell carcinoma subtypes.

PURPOSE: To assess the value of diffusion-weighted magnetic resonance imaging (DW-MRI) and contrast-enhanced MRI (CE-MRI) for differentiation between benign and malignant solid renal masses, renal cell carcinoma (RCC) subtypes, oncocytomas, and lipid-poor angiomyolipomas (LP-AML). METHODS: Minimum or lowest 'apparent diffusion coefficient' (ADC1) and representative ADC values (ADC2) of 112 renal masses (n: 46 benign renal mass, n: 66 malignant renal mass) were measured on DW-MRI images (b 50, 400, 800 s/mm2). Signal intensity (SI) measurements were performed in normal renal parenchyma and most avid enhanced area of the renal masses at precontrast, corticomedullary, and nephrographic phases on CE-MRI. Contrast enhancement rate (CER) and contrast enhancement index (CEI) values of renal masses were compared between benign-malignant renal masses and RCC subtypes, oncocytomas, and LP-AMLs. RESULTS: There was no significant difference between ADC1, ADC2 values, and SI of benign and malignant renal masses (p = 0.721, p = 0.255, p = 0.872). Mean ADC1 and ADC2 values of clear cell RCCs were significantly higher than nonclear cell RCCs (p = 0.005 p = 0.002). Mean CER value of clear cell RCCs was significantly higher than nonclear cell RCCs in nephrographic phase (p = 0.003). Mean CEI values of clear cell RCCs were significantly higher than nonclear cell RCCs in the corticomedullary and nephrographic phase (p = 0.027 vs. 0.008). LP-AMLs were differentiated from other renal masses with wash-out phenomenon. CONCLUSION: Combined usage of ADC, SI, CER, and CEI values may be useful for discrimination between RCC subtypes, oncocytomas, and lipid-poor AMLs.

Chronic renal failure and macrogenitalia associated with genitourinary neurofibromatosis.

Neurofibromatosis (NF) is a genetic disorder of the nervous system that primarily affects the development and growth of neural cell tissues. This disorder is characterized by the development of various tumors, including neurofibromas, neuroniomas, malignant and benign peripheral nerve sheath tumors, and meningiomas. Accompanying skin changes and bone deformities are also common in NF. However, genitourinary involvement in NF is a rare condition, and penile enlargement has been reported only in a few males with plexiform NF. We report a 6-year-old boy with chronic renal failure associated with plexiform neurofibromas of the bladder and prostatic urethra which led to urinary obstruction and macrogenitalia due to genitourinary NF.

Does the testicular apoptotic index vary with serum gonadotropins and testicular histopathology in infertile men?

AIMS: Testicular apoptosis has been shown in human specimens, but its correlation with serum gonadotropins and testosterone levels has not been studied. The aim of this study was to evaluate the relationship of apoptosis with serum hormone levels and testicular histopathological findings in infertile men. METHODS: Testis biopsy specimens were obtained for routine clinical purposes from 41 azoospermic men. The biopsy material was divided into two parts: one part was fixed in Bouin's solution and processed using paraffin embedding and HE staining, and the other was fixed in 10% neutral buffered formalin and embedded in paraffin for the detection of apoptosis using TUNEL. To determine the apoptotic index, the number of apoptotic cells was divided by the total number of the counted cells and multiplied by 100 to calculate the percentage. RESULTS: The apoptotic index was significantly higher in specimens with maturation arrest than in those with normal spermatogenesis (p = 0.016), hypospermatogenesis (p = 0.05), and Sertoli-cell-only specimens (p < 0.001). A significant negative correlation was found between serum follicle-stimulating hormone levels and the apoptotic index (r = -0.356, p = 0.01). CONCLUSION: Our results demonstrate there is a relationship between increased apoptosis and testicular dysfunction, and indicate a prominent role for apoptosis in human male infertility.

Multi-center evaluation of oxidation-reduction potential by the MiOXSYS in males with abnormal semen.

According to the World Health Organization (WHO), oxidative stress (OS) is a significant contributor to male infertility. Seminal OS can be measured by a number of assays, all of which are either costly or time sensitive and/or require large semen volume and complex instrumentation. One less expensive alternative is to quantify the oxidation-reduction potential (ORP) with the MiOXSYS. In this international multi-center study, we assessed whether ORP levels measured by the MiOXSYS could distinguish semen samples that fall within the 2010 WHO normal reference values from those that do not. Semen samples were collected from 2092 patients in 9 countries; ORP was normalized to sperm concentration (mV/106 sperm/ml). Only those samples with a concentration >1 × 106 sperm ml-1 were included. The results showed that 199 samples fell within the WHO normal reference range while the remaining 1893 samples did not meet one or more of the criteria. ORP was negatively correlated with all semen parameters (P < 0.01) except volume. The area under the curve for ORP was 0.765. The ORP cut-off value (1.34 mV/106 sperm/ml) was able to differentiate specimens with abnormal semen parameters with 98.1% sensitivity, 40.6% specificity, 94.7% positive predictive value (PPV) and 66.6% negative predictive value (NPV). When used as an adjunct to traditional semen analysis, ORP levels may help identify altered functional status of spermatozoa caused by OS in cases of idiopathic male infertility and in male partners of couples suffering recurrent pregnancy loss, and thereby directing these men to relevant medical therapies and lifestyle modifications.

Value of Shear Wave Elastography for differentiating benign and malignant renal lesions.

AIMS: To investigate the diagnostic accuracy of shear-wave elastography (SWE) for assessing malignant and benign kidneymasses. MATERIALS AND METHODS: Forty patients with solid renal masses underwent US elastographic evaluation. SWE values of the lesions and adjacent cortical renal parenchyma and SWER were detected prospectively. Malignant tumors were recorded as group 1 and benign tumors were recorded as group 2. RESULTS: The highest elasticity values were 27.27±25.66 kPa for group 1 and 16.13±8.89 kPa for group 2. The mean±SD elasticity values for adjacent renal cortex for groups 1 and 2 were 2.7±2.08 and 2.75±1.35, respectively. For group 1, a negative correlation was observed between the age of the patients and SWER value (p=0.047, rs=­0.401). There was also a negative correlation between the SWER value and the SWE value of adjacent renal cortex (p=0.004, rs=­0.555). CONCLUSION: SWE is a noninvasive method that provides quantitative elasticity informationon tissues. Overlaps among different types of renal lesions may be due to heterogeneity of the lesions. Larger studygroups may clarify the other factors affecting SWE values under both normal and pathological conditions.

Roles of Signal Transducer Pathways in Investigation of Biopsies from Patients with Bladder Tumors

Background:The process of development of bladder cancer features alteration of normal biological conditions caused by changes in molecular pathways. Removing control over regulation of these pathways could lead to changes in signal transduction and abnormal regulation of genes. During tumor formation and progression, genes regulate critical cellular processes, involved in cell cycling, growth and death. Here we evaluated the expression and prognostic importance of FGFR1, HRAS, CCND1, CCND3, STAT3 and FAS genes. Methods: Tumor tissues of 44 patients diagnosed with bladder cancer were investigated for changes in expression levels of FGFR1, HRAS, CCND1, CCND3, FAS and STAT3 genes by the RT-PCR method. Signal transduction pathways and expression of individual genes related to these pathways were analyzed using the "One Sample Test". Results: There were statistically significant changes in the expression levels of HRAS, CCND1, CCND3 and STAT3, but not FGFR1 and FAS genes. Examination of associations with age, gender, smoking, chemotherapy, tumor grade and tumor growth pattern using the "Independent Samples Test", showed importance relations between the CCND1 gene and cigarette smoking and sex. Conclusion: Over-expression of HRAS, CCND1, CCND3 and STAT3 genes may play roles in bladder cancer development and progression, while cigarette smoking is significantly associated with CCND1 gene expression and consequently concluded to be contributing to the development of bladder cancer.

Dose-response relationship between testosterone and erectile function: evidence for the existence of a critical threshold.

Androgens play an important role in erectile function. However, the dose-response relationship between plasma testosterone levels and penile erection remains unclear. Intact (sham operated) or bilaterally orchiectomized, mature male Sprague-Dawley rats were used. Two weeks after surgery, rats were infused continuously with either vehicle (polyethyleneglycol) or varying doses of testosterone (44, 88, 220, or 440 mug/day) for 14 days using subcutaneous osmotic infusion pumps (study 1). In a separate study, 4 weeks after surgery, rats were infused with a lower range of testosterone doses (11, 22, or 44 mug/day) for 14 days (study 2). In the first study, intact rats had a mean plasma testosterone concentration of 0.56 +/- 0.12 ng/mL ( approximately 1.9 nM), as determined by standard radioimmunoassay. In the second study, a more sensitive enzyme-linked immunoassay was used to measure the lower testosterone levels. Using this assay, intact rats had a mean plasma testosterone concentration of 2.02 +/- 0.59 ng/mL. Intracavernosal pressure measurements indicated that orchiectomy resulted in a significant reduction in erectile function, when compared to intact animals, whereas testosterone infusion restored erectile function to varying degrees. Erectile function was maintained by a wide range of systemic testosterone levels as low as 10%-12% of normal physiological plasma concentrations. Below these concentrations, erectile function was significantly and positively correlated with testosterone plasma levels in a dose-dependent manner. Interestingly, prostate tissue mass was positively correlated to plasma testosterone levels across all concentrations examined. Protein expression of neural nitric oxide synthase (nNOS) and phosphodiesterase type 5 (PDE 5) was reduced in penile tissue from orchiectomized animals and increased in testosterone-infused animals, as assessed by Western blot analyses. We suggest that testosterone at levels approaching one-tenth normal physiological plasma concentration may represent a threshold value, below which erectile function declines in a dose-dependent fashion. However, different androgen-dependent tissues may exhibit varying sensitivities to circulating testosterone with regard to growth and function.