The cellular transcription factor Brn-3a and the smoking-related substance nicotine interact to regulate the activity of the HPV URR in the cervix.

The cellular transcription factor Brn-3a differentially regulates different human papilloma virus (HPV)-16 variants that are associated with different risks of progression to cervical carcinoma in infected humans. The upstream regulatory regions (URRs) of high- and intermediate-risk HPV-16 variants are activated by the cellular transcription factor Brn-3a, whereas the URR of a low-risk HPV-16 variant is not. In this study, we show in transfection assays that Brn-3a and the smoking-related substance nicotine produce stronger responsiveness of the URR of the low- and high-risk variants than with either factor alone, but not the intermediate-risk variant. We determined that this synergistic activity of Brn-3a/nicotine is due to two nucleotide differences in the URR, crucial for oncogenic E6/E7 transactivation. Mutant constructs in which the nucleotide residues were substituted alter Brn-3a/nicotine responsiveness. Importantly, women smokers with high levels of Brn-3a infected with low- or high-risk HPV-16 variants have augmented E6 levels, and were more frequently diagnosed with higher grades of cervical intraepithelial neoplasia (CIN) and cancer, as compared with non-smokers who were infected with similar variants and expressed similar levels of Brn-3a. Therefore, this study defines the specific interplay between the cellular transactivator Brn-3a, the environmental smoking-related substance nicotine and specific HPV variants in cervical carcinogenesis, and thus helps to explain why some women are susceptible to rapid CIN progression and cancer and others are not.

Transperitoneal unstented ureteral reimplantation for injuries postgynecological surgery.

Pelvic ureteral injuries represent a serious surgical accident due to the potential damage they may cause to renal function. We report here the results of 19 years of experience with reconstruction of distal ureteral injuries by transperitoneal unstented reimplantation. This was a prospective cohort study undertaken at Barão de Lucena and University Hospitals, Recife (Brazil). Forty-seven patients with ureteral obstruction postgynecological surgery were routinely operated using the initial incision. The ureter was identified, dissected, and reimplanted through the peritoneal cavity. No stent was necessary. The average surgical time was 70 min (45-180 min). A psoas hitch or a Boari-Ockenblad bladder flap was required in six (12.8%) and four (8.5%) patients, respectively. Among 32 patients without fistula, 28 (87.5%) had complete and four (12.5%) had partial hydronephrosis regression without clinical repercussions. The cure rate was 100%. There were no complications. Routine primary unstented distal ureteral reimplantation using the transperitoneal approach is an effective and safe treatment strategy for injuries following benign gynecological surgery.

Cervical cancer detection by hybrid capture and evaluation of local risk factors.

UNLABELLED: The city of Recife, northeastern Brazil, is reported to have the highest incidence of cervical cancer worldwide (83.2/100000 women). OBJECTIVE: To evaluate the efficacy of Hybrid Capture I (HC I) in cervical cancer detection and some risk factors in Recife. METHOD: Cervical scrapes for HC I analysis followed by colposcopy were collected from 140 women (70 with cervical cancer and 70 with normal cervix) from three screening services in Recife. RESULT: HC I sensitivity and specificity were 82.9 and 41.4%, respectively. The odds ratios for cervical cancer when Gesta > or = 5 and vaginal parity > or = 4 were, respectively, 5.30 and 4.27. CONCLUSION: HC I is a moderately sensitive method to detect cervical cancer, but it does not seem to be useful as a primary screening tool for it's low specificity. Early pregnancy, high Gesta/Para and living in rural areas were important local risk factors.

Perineal assessment of urethrovesical junction mobility in young continent females.

This paper describes the application of perineal ultrasound (7 MHz transducer) in the assessment of the urethrovesical junction (UVJ) in 40 continent nulliparous females. Measurements of UVJ vertical and horizontal movements were assessed in relation to the inferior border of the pubic symphysis from resting to the maximum straining position. Participants were examined in the dorsal lithotomy position with no more than 50 ml of urine in the bladder. Volunteers' average age was 16 years (range 10-25). The mean vertical movement was 5.3+/-2.4 mm (maximum 9 mm). In 95% of participants the measurement for horizontal movement did not exceed 11.2 mm. Perineal ultrasound in patients with the bladder practically empty is an easy way to assess urethrovesical junction mobility objectively. It avoids the possible influence of detrusor contraction. A standard method for this assessment can provide accurate essential information for classification, management and follow-up of urinary incontinence.

Female urethral reconstruction with amnion grafts.

BACKGROUND: About 1-5% of female babies are born with Müllerian duct abnormalities such as Mayer-Rokitansky-Küster-Hauser syndrome, urogenital sinus, and cloacal malformation. In some intersex cases the urethra and vagina both empty into a urogenital sinus. One major issue in single-stage surgical reconstruction of large urethral defects is tissue availability. AIM: To investigate the usefulness of amnion grafts in female urethral reconstruction. METHODS: This is a prospective cohort study describing the use of amnion grafts for urethral reconstruction in 8 patients with ambiguous genitalia associated with low or mid-portion urethrovaginal confluence or vaginal agenesis with low external urethral meatus implantation. RESULTS: The procedure was felt to be easy, quick and effective for appropriate restoration of both the function and the cosmetics of the lower urogenital tract. CONCLUSIONS: Amnion grafts add a valuable option to the surgical armamentarium and offers potential advantages for urogenital reconstructive surgery.

The use of human papillomavirus typing in detection of cervical neoplasia in Recife (Brazil).

High risk types of human papillomavirus (HR-HPV) play a major role in cervical cancer oncogenesis. This study aims to evaluate the efficacy of HPV detection and typing as a means of identifying cervical neoplasia in a high risk population. A management algorithm for implementation of HPV detection in clinical practice is also proposed. A nested case-control within a cohort study was undertaken in Recife (Brazil). All 479 participants had cervical scrapes collected for HPV detection followed by colposcopy. Samples were blindly analyzed by polymerase chain reaction (PCR) and typed by restriction fragment length polymorphism (RFLP). HPV detection by PCR and typing with RFLP cost US$ 4.92 per woman screened in this study and is significantly better than cytology in identifying women at risk of developing cervical cancer (P = 0.0001). Women who tested positive for HR-HPV had over 35-fold increased risk of having high grade squamous intraepithelial lesion (HSIL) or cervical cancer, although this does not necessarily translate into the same risk rate for women with latent HPV infection developing major cervical neoplasia. HPV typing offers 90% sensitivity and 85% specificity for cervical cancer detection. In combination with cytology it provides a negative predictive value of 99.4% and a sensitivity of over 96% for detection of HSIL and cervical cancer. We conclude that HPV typing is an inexpensive and effective method for identification of cervical neoplasia and women at risk of developing it. It improves quality control for both false negative and false positive cytology results. Routine screening intervals could safely be increased to 3-5 years, decreasing anxiety and socio-economic inconveniences.

Treatment of vesicovaginal fistula by bladder mucosa autograft technique.

OBJECTIVES: We evaluated the efficacy of the bladder mucosa autograft technique in the treatment of vesicovaginal fistula. STUDY DESIGN: During 15 years, 80 women with vesicovaginal fistula after gynecologic surgery for benign disease were treated by interposition of a bladder mucosa autograft in the fistulous tract within 1-3 months of its genesis. RESULTS: The success rate of this surgical intervention was 96.3%. There was no late failure. CONCLUSIONS: Bladder mucosa autograft interposition seems to be an excellent therapy for closing vesicovaginal fistulas. It appears to be more physiologic and easier to perform when compared with other transabdominal techniques. Early intervention proved to be efficacious and to improve the woman's quality of life.