TIMP-2 gene methylation in cervical precursor and invasive lesions.

OBJECTIVE: To analyze the presence of HPV-DNA and TIMP-2 gene methylation in cervical precursor and invasive lesions, as well as to study the associations among the latter, the presence of HPV-DNA, and the clinical evolution of such lesions. METHODS: Cross-sectional study that includes 49 biopsy or brush smear samples from women with a normal cervix, LSIL, HSIL, microinvasive carcinoma and invasive carcinoma. The presence of HPV-DNA and specific methylation was analyzed using PCR. Thirty-eight biopsy samples for HSIL, microinvasive carcinoma and frank invasive carcinoma as well as 11 brush smear samples for LSIL and normal cervices were analyzed. RESULTS: TIMP-2 gene methylation was detected in 86.8% (33/38) of the samples from the group with lesions and 50% (4/8) of the normal samples (p=0.03). HPV-DNA was detected in 81.6% (31/38) of the samples from the group with lesions and 25% (2/8) of the normal samples (p=0.003). HPV-DNA was more frequent in the methylated samples (50%), and the group with methylation had a higher risk of unfavorable evolution than the group without methylation; however, such observations were not statistically significant (p=0.19). CONCLUSION: TIMP-2 gene methylation and the presence of HPV-DNA were characteristic of the group with cervical lesions. Methylation was not associated with the presence of HPV-DNA or an unfavorable clinical evolution.

Surgical treatment for unstable pelvic fractures in skeletally immature patients.

OBJECTIVE: To present the results and conclusions of our study on surgical treatment for unstable pelvic fractures in children subjected to surgical reduction and stabilisation. METHODS: We analysed the cases of fourteen skeletally immature patients with unstable pelvic fractures who underwent surgery for this condition between March 2004 and January 2011. The surgical technique used was based on the principle of surgical reduction and stabilisation of anterior and posterior lesions of the pelvic ring. This was a retrospective study, based on clinical assessment and X-ray analyses. RESULTS: The mean age of patients at the time of the condition was 9.4 years (range 2-13 years). Eight patients were female and six were male. The cause of the trauma was being hit by a car in ten cases, falls in three cases and an accident involving a motorcycle in one case. Five patients presented with other associated injuries, including fracture of the clavicle, femur shaft, proximal humerus, tibial shaft or olecranon, and bladder damage. All the patients assessed showed excellent clinical progress. Pelvic asymmetry prior to surgery varied from 1.1 to 2.9 cm (mean 1.5 cm) and dropped to a range of 0.2 to 0.9 cm (mean 0.4 cm) after reduction. In none of the cases was there a change between the pelvic asymmetry measured immediately after surgery and at the end of the follow-up period. CONCLUSION: Pelvic fracture in skeletally immature patients is rare and surgery is not normally indicated. Various authors have questioned this conservative type of treatment due to complications encountered. Bone remodelling does not seem to be sufficient to ensure an improvement in pelvic asymmetry, which justifies opting for surgery to reduce and correct deformities in the pelvic ring.

Evaluation of DAPK gene methylation and HPV and EBV infection in cervical cells from patients with normal cytology and colposcopy.

OBJECTIVE: Evaluation of promoter methylation of the death-associated protein kinase (DAPK) gene and HPV and EBV infections in cervical cells from patients with normal cytology and colposcopy. STUDY DESIGN: Twenty women, who had been patients at the Institute of Gynecology of the Federal University of Rio de Janeiro (UFRJ) for routine examinations and who showed normal cytology and colposcopy, were selected for this work. Cervical brushings were used for DNA extraction, and the analysis of methylation patterns of the DAPK gene was done through chemical modification with sodium bisulfite. Analysis of viral infection was done using polymerase chain reaction (PCR). RESULTS: Of the 20 patients studied, six (30%) presented methylation of the DAPK gene, five (25%) presented infection with EBV and three (15%) presented coinfection with HPV/EBV. Associating methylation with viral infection, we found methylated DAPK in one patient (16%) with EBV, in two patients (33%) with co-infection and in three patients (50%) with no viral infection. CONCLUSIONS: In the present study, we verified, for the first time, the methylation pattern of the DAPK gene in cervical smears from patients with normal cytology and colposcopy. The results also showed the presence of viral infections in these patients. EBV infection, irrespective of whether associated with HPV or not, may contribute to cervical carcinogenesis as a cofactor. Methylation of the DAPK gene is associated with cell transformation, suggesting that DAPK methylation might be an important marker for the development of cervical epithelial neoplasias.