Combined point mutations in codon 12 and 13 of KRAS oncogene in prostate carcinomas.

Prostate cancer is a common malignancy that develops by structural mutation(s) and/or other genetic alterations in specific genes.The G to T transversions in codon 12 and C to T transitions in codon 13 of KRAS proto-oncogene are predominant point mutations that occur in about 20% of different cancers in human. In the current study it was aimed to investigate the prevalence and predictive significance of KRAS mutations in patients with prostate carcinomas. In a total of 30 fresh tumoural tissue specimens were investigated in patients with prostate carcinoma. All tumoural specimens were histo-pathologically diagnosed and genotyped for codon 12, 13 KRAS point mutations by reverse hybridisation and direct sequencing methods. KRAS mutations were found in 12 (40%) samples with 29 samples deriving from adenocarcinomas and 1 sample was small cell prostate carcinoma. In 1 (3.44%) sample codon 12 was found to be mutated and in 2 (6.8%) samples codon 13 and in 9 (31%) samples combined codon 12 and 13 were found to be mutated particularly in higher grade of tumoural tissues. Our study, based on representative collection of human prostate tumours, indicates that combined mutations in codons 12 and 13 KRAS are relatively infrequent and most commonly occur in prostate carcinomas.

A comparison of sedation with dexmedetomidine or propofol during shockwave lithotripsy: a randomized controlled trial.

BACKGROUND: Dexmedetomidine, because it has both sedative and analgesic properties, may be suitable for conscious sedation during painful procedures. Extracorporeal shockwave lithotripsy (ESWL) is a minimal to mildly painful procedure that requires conscious sedation. We thus evaluated the utility of dexmedetomidine compared with propofol during an ESWL procedure. METHODS: Forty-six patients were randomly allocated into two groups to receive either dexmedetomidine or propofol for elective ESWL. Dexmedetomidine was infused at 6 microg x kg(-1) x h(-1) for 10 min followed by an infusion rate of 0.2 microg x kg(-1) x h(-1). Propofol was infused at 6 mg x kg(-1) x h(-1) for 10 min followed by an infusion of 2.4 mg x kg(-1) x h(-1). Fentanyl 1 microg/kg IV was given to all patients 10 min before ESWL. Pain intensity was evaluated with a visual analog scale at 5-min intervals during ESWL (10-35 min). Sedation was determined using the Observer's Assessment of Alertness/Sedation. The Observer's Assessment of Alertness/ Sedation scores and hemodynamic and respiratory variables were recorded regularly during ESWL (35 min) and up to 85 min after. RESULTS: Forty patients were evaluated. Visual analog scale values with dexmedetomidine were significantly lower than those with propofol only at the 25-35 min assessments (P < 0.05). During sedation, the respiratory rate with dexmedetomidine was significantly slower but Spo2 was significantly higher than with propofol (P < 0.05). Other clinical variables were similar (P > 0.05). CONCLUSION: A combination of dexmedetomidine with fentanyl can be used safely and effectively for sedation and analgesia during ESWL.

Effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on apoptotic changes in contralateral testis following unilateral testicular torsion.

OBJECTIVES: In this experimental study, our aim was to determine whether angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 (AT1) receptor blockade affect the apoptotic changes in contralateral testis following unilateral testicular torsion (UTT). METHODS: Study groups consisted of 30 adult male Wistar rats. The rats were randomly separated into five groups. Group 1 was maintained as control without manipulation. Group 2 underwent the sham operation. Torsion was created by rotating the left testis 720 degrees clockwise for 4 h and maintained by fixing the testis to the scrotum in the other groups. Group 3 underwent torsion and detorsion, with saline administration after detorsion. In group 4, the same surgical procedure was done as in the detorsion group, but AT1 receptor blocker (losartan 30 mg/kg) was injected intraperitoneally for 60 min before detorsion. In group 5, the same surgical procedure was done as in the detorsion group, but ACE inhibitor (lisinopril 50 mg/kg) was injected intraperitoneally for 60 min before detorsion. Bilateral testes were removed from each rat 24 h after surgery. Apoptosis was assessed in paraffin-embedded sections stained for TUNEL method. Reticulum staining was performed to evaluate the extracellular changes semiquantitatively. Testicular biopsy score counts were performed on these sections according to Johnsen. RESULTS: The mean apoptotic scores of group 1, group 2 and group 3 were significantly higher than that of the other groups. There was no difference between the apoptotic scores of groups 1, 2, 4 and 5. Reticulum stain was increased in group 3 as compared to other groups. The mean Johnsen biopsy score of group 3 was significantly lower than that of the other groups. CONCLUSION: ACE inhibition and AT1 receptor blockade reduced the tubular damage and apoptosis in the contralateral testes after UTT. The beneficial effect of these drugs may arise from inhibition of ischemic process resulting from increased sympathetic activity and elimination of insults subsequent to dysregulation of RAS. These results suggest that ACE inhibitors and AT1 receptor blockers may be of potential value in patients with UTT.

Comparison of CT-guided sclerotherapy with using 95% ethanol and 20% hypertonic saline for managing simple renal cyst.

OBJECTIVE: We wanted to compare the efficacies of 95% ethanol and 20% hypertonic saline (HS) sclerotherapies that were performed in a single session under CT guidance for the management of simple renal cysts. MATERIALS AND METHODS: A prospective series of 74 consecutive patients (average age: 57.6 +/- 8.1 years) with simple renal cysts were enrolled in this study. They were randomized into two groups and 95% ethanol or 20% HS, respectively, corresponding to 25% of the aspiration volume, was injected. Treatment success was determined six months later with follow-up clinical evaluation and performing ultrasonography. RESULTS: The sclerotherapy was accepted as technically successful without major complications in all except two patients who were excluded because of a communication between the simple renal cyst and the pelvicalyceal collecting system. Thirty-six patients in the ethanol group received sclerotherapy with 95% ethanol and 36 patients in the HS group underwent sclerotherapy with 20% HS. The complete regression ratio of the ethanol group was significantly higher (94% versus 72%, respectively) than that of the HS group. There was one patient with partial regression in each group. The failure ratio of the ethanol group was significantly lower (3% versus 25%, respectively) than that of the HS group. CONCLUSION: Ethanol sclerotherapy under CT guidance is a successful and safe procedure and it can be used for the treatment of simple renal cysts. Sclerotherapy with 95% ethanol is more effective than 20% HS sclerotherapy. Sclerotherapy with HS may be an option for patients preferring to undergo a less painful treatment procedure.

[Surgical treatment of penil fractures]. / Penis fraktürlerinin cerrahi tedavisi.

BACKGROUND: Patients diagnosis as penil fracture and treated with surgical methods were evaluated retrospectively between January 1990-February 2002. METHODS: Patients were evaluated by age, trauma type, time passed after the trauma, physical examination and radiologic data. RESULTS: The cause of trauma was blunt trauma in all patients. 14 trauma (60.8%) were during sexual activity, 6 trauma (26%) were during handling the erective penis in morning erection, 3 of trauma (13%) were due to the rolling on to the penis. Urethral bleeding was seen in 1 patient and microscopic hematuria was detected in 5 patients. Subcoronal circular incision was carried out in 16 patients (69.5%), semicircular incision was done directly on the injury in 6 patients (26%) and from penis radix to scrotum was done in 1 patient (4.3%). There was unilateral corpus cavernosum injury in 21 patients. Bilateral corpus cavernosum injury in 1 patient, corpuscavernosum, corpus spongiosum and incomplent urethral injury in 1 patient. Wound infection was detected only in 2 patients at postoperatively early period. After evaluating 20 patients with medical history and physical examination in postoperative control penil curvature permitting sexual activity was detected in 3 patients. CONCLUSION: We concluded that patients with penil fracture may be treated with low complication rate by early surgical procedure.

Alterations in promoter methylation status of tumor suppressor HIC1, SFRP2, and DAPK1 genes in prostate carcinomas.

Hypermethylated genomic DNA is a common feature in tumoral tissues, although the prevalence of this modification remains poorly understood. We aimed to determine the frequency of five tumor suppressor (TS) genes in prostate cancer and the correlation between promoter hypermethylation of these genes and low and high grade of prostate carcinomas. A total of 30 prostate tumor specimens were investigated for promoter methylation status of TS hypermethylated in cancer 1 (HIC1), death-associated protein kinase 1 (DAPK1), secreted frizzled-related protein 2 (SFRP2), cyclin-dependent kinase inhibitor 2A (p16), and O-6-methylguanine-DNA methyltransferase (MGMT) genes by using bisulfite modifying method. A high frequency of promoter hypermethylation was found in HIC1 (70.9%), SFRP2 (58.3%), and DAPK1 (33.3%) genes in tumor samples that were examined. The current data show high frequency of hypermethylation changes in HIC1, SFRP2, and DAPK1 genes in prostate carcinomas of high Gleason Score (GS).

Efficacy of tolterodine as a first-line treatment for non-neurogenic voiding dysfunction in children.

OBJECTIVE: To assess the effect of antimuscarinic treatment with tolterodine combined with behavioural modification as a first-line treatment, before invasive investigation, in children with non-neurogenic voiding dysfunction but no obvious anatomical or neurogenic cause. PATIENTS AND METHODS: The study comprised 44 children presenting with voiding dysfunction (30 girls and 14 boys, mean age 7 years, range 5-14); all had a noninvasive evaluation consisting of a history, urine analysis, renal and bladder ultrasonography and physical examination, with specific emphasis on the voiding pattern. Anticholinergic treatment with tolterodine (1 mg twice daily) was started in all patients; they were also informed about conservative management, including timed voiding, double voiding and relaxation of the pelvic floor during voiding. At the start and after 3 months, the dysfunctional voiding symptom score (DVSS) was completed twice by all patients. RESULTS: For all patients the mean (sd) DVSS was 14.0 (2.67) and 6.68 (3.67) before and after treatment, respectively; the difference was statistically significant (P < 0.001). The mean scores for girls and boys, respectively, were 13.8 (2.79) and 14.5 (2.44) before and 6.43 (3.79) and 7.50 (3.34) after treatment. CONCLUSION: Tolterodine combined with behavioural modification for dysfunctional voiding in children with no neurological or anatomical abnormality can be recommended as a first-line treatment before invasive evaluation. Additionally, the DVSS appears to provide accurate and objective data for monitoring the effect of treatment in such children.