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Sildenafil is the oral phosphodiesterase-5 inhibitor that revolutionized treatment for erectile dysfunction. We investigated a potential association of the G protein beta 3 subunit (GNB3) C825T polymorphism, a determinant of intracellular signal transduction, with the drug response to sildenafil in patients with erectile dysfunction.In 113 men with erectile dysfunction and 111 healthy male controls genotype status of the GNB3 C825T polymorphism was determined by polymerase chain reaction and restriction analysis. Patients with erectile dysfunction received sildenafil at a dose of 25 to 100 mg. according to the individual erectile response. Drug response was measured by interviewing the patient according to the erection scale of 0 to 5.The GNB3 genotype distribution of patients with erectile dysfunction exactly matched that of healthy controls. Analysis of the response to sildenafil revealed a significant association of C825T allele status with the erectile response to sildenafil. In the group with TT genotype we observed a 90.9% response but only a 50.9% and 48.9% response in patients with the CC and TC genotype, respectively. The odds ratio for a positive erectile response was 10.0 (95% CI 1.2 to 81.1) for patients with the TT versus the TC/CC genotype (p = 0.01).The response to sildenafil is significantly associated with GNB3 C825T genotype status in patients with erectile dysfunction.

To identify and analyse point mutations in p53 tumour suppressor gene (Tp53) in benign prostatic hyperplasia (BPH) by temperature gradient gel electrophoresis (TGGE) and sequence.141 tissue specimens (approx. 100 mg) after transurethral resection of the prostate (TURP), 12 specimens after needle biopsy. Control samples for genetic analysis were (a) 7 prostate tissues without any sign of BPH and malignancy and (b) 103 prostate cancer (PCa) tissues. DNA of the critical Tp53 exons 5-8 was amplified and run on horizontal polyacrylamide gels under defined temperature conditions (TGGE) to yield specific gel shifts and sets of homo- and heteroduplexes in case of mutation. Sequencing with a laser-fluorescent electrophoresis unit was done from re-amplified mutant and wild-type bands.TGGE screening of 153 BPH samples identified 29 specimens with Tp53 mutations (5 in exon 5, 11 in exon 6, 12 in exon 7, 3 in exon 8; 1 tissue sample showed mutations in 3 exons at a time). The computed mutation frequency was 19.0%. Two patients, with mutation in BPH tissue, developed PCa 2-3 years after TURP. One patient with mutation in BPH tissue developed bladder cancer. Of 118 patients with non-mutated DNA in BPH, none is known to have a urological cancer. The Tp53 mutation frequency in 103 PCa samples was 26.2%. Significant differences of mutation frequency between BPH and PCa were detected only in lower exon 5 mutation counts in BPH.Tp53 mutation in BPH tissue may be a tumour risk factor.

We assessed the predictive value of TP53 mutations and prostate-specific antigen (PSA) for tumor progression in prostate cancer (PCa) patients.Ninety tumor tissue samples of patients with PCa from radical prostatectomy were used. Tumor progression was estimated biochemically by the PSA level (0.2 microg/l) or by detection of metastases. Screening for TP53 mutations was performed by temperature gradient gel electrophoresis (TGGE) in exon-specific manner. Follow-up data were collected from medical protocols. Statistical analysis was performed by uni- and multivariate techniques.In 32 out of 90 patients (35.6%), TP53 mutations were detected. Thirteen out of 32 patients (40.6%) with TP53 mutations and nine out of 58 patients (15.5%) with TP53 wild-type showed tumor progression after 25 and 45 months, respectively.TP53 mutations in exon 7 and exon 8 are factors of tumor progression in PCa. Their contribution to tumor recurrence is more significant than tumor stage and pretherapeutic PSA level.

This study evaluates the influence of the TP53 genetic status on tumour recurrence and progression with a highly effective electrophoretic technique. DNA from tissue of 75 non-invasive urinary bladder cancers was PCR amplified in the TP53 exons 5-8 and run on horizontal polyacrylamide gels under defined temperature conditions to yield specific gel shifts. Kaplan-Meier and Cox-Regression analysis were performed with tumour progression. The overall tumour recurrence in our patient population was 76.0% (57/75). Tumour recurrence frequency was 69.4% (34/49) in patients with TP53 wild-type, and 88.5% (23/26) in patients with TP53 mutation. There was no statistically significant difference with regard to recurrence frequency and time to recurrence. The progression-free survival was significantly shorter in patients with TP53 mutations, and the frequency of tumour progression was significantly higher in mutated as compared to wild-type tumours. Cox-Regression analysis showed a significant and independent influence of TP53 mutation on tumour progression in comparison with tumour grade, stage and history of prior bladder cancer. If segregated by exons, mutations in the DNA binding region of exon 8 seem to have a particular high influence on tumour progression. We conclude that genetic analysis of TP53 can select patients at high risk of bladder tumour progression that should be followed closely and may benefit from early radical surgical procedures.

The predictive value of TP53 mutations and prostate-specific antigen (PSA) was assessed in prostate needle biopsies of samples without signs of malignancy for later affliction by prostate cancer (PCa). Comparison of mutation frequency and PSA level in prostate needle biopsies with data of patients with benign prostate hyperplasia (BPH) treated by transurethral resection (TURP), patients with prostatic intraepithelial neoplasia (PIN), and patients with PCa, was made.A total of 466 samples were analysed from patients with benign and malignant diseases of the prostate, including 52 samples of needle biopsies of the prostate with repeated benign histopathological diagnosis. Analysis of TP53 state by temperature gradient gel electrophoresis of TP53 exon-specific PCR products of exons 5, 6, 7 and 8 was performed. Clinical follow-up of 100 patients with benign diseases of the prostate and with PIN was available.Needle biopsy samples with repeated benign diagnosis resemble BPH specimens taken by TURP in TP53 mutation frequency (TURP: 16.1%, needle biopsy: 21.2%) and later affliction by PCa (TURP: 3/32 = 9.4%, needle biopsy: 8/51 = 15.7%, p = 0.409). Patients with TP53 mutations in needle biopsy samples showed a significantly reduced disease-free survival time for affliction by PCa (log rank: p = 0.0149). This significance is raised by computing exon 6 mutations only with respect to affection by PCa (p = 0.0002). In TURP patients, exon 7-mutations were also significant (p = 0.0086). Needle biopsy TP53 mutations (p = 0.029) had significant predictive values for later affliction by PCa in multivariate analysis. PSA level and patient age had no predictive value for PCa.TP53 mutations reduce the PCa-free survival time in patients with needle biopsy of the prostate and primary benign diagnosis. Exon 6 mutations enhance the risk of being affected by PCa 32-fold.

Partial segmental thrombosis of the corpus cavernosum is a rare disease of unknown etiology; the thrombosis is always located in the proximal part of the corpus cavernosum, usually unilaterally. Typical clinical presentation with perineal pain and swelling in combination with cross-sectional imaging allows one to confidentially establish this diagnosis.

Objective Obesity is estimated to account for up to 20% of all cancer deaths. Mutations of TP53 are frequently correlated with tumor development and progression. We evaluated the effect of body mass index (BMI) and mutation status of tumor suppressor gene p53 (TP53) on patients with urinary bladder cancer. Materials and methods Clinical samples were used from 75 patients with tumors of the urinary bladder. Mutation status in TP53 exons 5, 6, 7, and 8 was analyzed by temperature gradient gel electrophoresis of exon-specific PCR products and by sequence analysis. Statistical analysis included Pearson's correlation. Results For noninvasive bladder cancer, the mutation frequency in TP53 was 44.6%, while for invasive bladder cancer the mutation frequency in TP53 was 84.2%. Normal weight, overweight, and patients with obesity had a TP53 mutation frequency of 68.4%, 44.8%, and 25%, respectively (P Conclusions TP53 mutation frequently occurs in higher stages of bladder tumors. Body mass index is not associated with a higher TP53 mutation frequency in our study, but BMI should be included for collecting data of bladder cancer risk profile.

The authors evaluated a magnetic resonance (MR) imaging-compatible biopsy device comprising a needle guide that can be visualized with MR imaging and manipulated mechanically from outside the MR unit. With approval from the local ethics committee and patient consent, this device was tested in 12 patients by using a closed 1.5-T MR unit and a body phased-array coil. Patients had elevated prostate-specific antigen levels (6-60 ng/mL) and one or more areas in the prostate that were suspicious for carcinoma at prebiopsy MR imaging. Biopsy was performed with transrectal access and with the patient prone. A 16-gauge MR imaging-compatible needle was successfully positioned with the device, and between six and nine tissue cores were obtained in each patient. In one patient, two suspicious basal areas could not be reached with the device. Histologic analysis showed prostate cancer in five patients and prostatitis in six. No complications were observed. The device enabled MR imaging-guided core-needle biopsy of prostate areas suspicious for cancer on MR images.

A 24-kDa heparin binding protein recently identified as tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in bovine seminal fluid was suggested to play an important role in bull fertility. As no data are present for men, the concentrations of tissue inhibitors of metalloproteinases 1 (TIMP-1) and TIMP-2 were quantified in human seminal plasma of normozoospermic and azoospermic men using enzyme-linked immunosorbent assay methods. TIMP-1 and 2 were not significantly different in both groups and there were no relationships between the concentrations of both TIMPs and other sperm characteristics. It is assumed that TIMPs are released from accessory sex glands.

To determine the role of magnetic resonance (MR) imaging performed with a combined endorectal body phased-array coil for patients with elevated prostate-specific antigen (PSA) levels or suspicious free-to-total PSA ratios in whom prior transrectal ultrasonographically (US) guided biopsy findings were negative for prostate cancer.Forty-four patients with PSA levels greater than 4 ng/mL or free-to-total PSA ratios lower than 15% but negative biopsy findings were examined with T1- and T2-weighted MR imaging at 1.5 T with a combined endorectal body phased-array coil. All patients underwent digital rectal examination (DRE) and transrectal US. Thirty-eight patients underwent repeat biopsy after MR imaging. The accuracy of MR imaging for detection of prostate cancer was assessed prospectively. Retrospectively, MR imaging findings were correlated with individual biopsy site findings. MR imaging and biopsy results were correlated by using a cross table to calculate sensitivity, specificity, and positive predictive value (PPV). Retrospective analysis results were evaluated with receiver operating characteristic analysis. A P value of less than.05 indicated significance (chi(2) test according to Pearson).At prospective analysis, MR imaging had a sensitivity of 83% and a PPV of 50% for detection of prostate cancer; these values were 33% and 67%, respectively, for DRE and 33% and 57%, respectively, for transrectal US. At retrospective site-by-site analysis, MR imaging results did not correlate significantly with individual biopsy site findings (P =.126); sensitivity was 65% and PPV was 12%.In this patient population, MR imaging has higher sensitivity for detection of prostate cancer than DRE or transrectal US.