RESUMO
Objectives: The relation of serum androgens and the development of prostate cancer (PCa) is subject of debate. Lower total testosterone (TT) levels have been associated with increased PCa detection and worse pathological features after treatment. However, data from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) and Prostate Cancer Prevention (PCPT) trial groups indicate no association. The aim of this study is to investigate the association of serum androgen levels and PCa detection in a prospective screening study of men at higher genetic risk of aggressive PCa due to BRCA1/2 pathogenic variants (PVs), the IMPACT study. Methods: Men enrolled in the IMPACT study provided serum samples during regular visits. Hormonal levels were calculated using immunoassays. Free testosterone (FT) was calculated from TT and sex hormone binding globulin (SHBG) using the Sodergard mass equation. Age, body mass index (BMI), prostate-specific antigen (PSA) and hormonal concentrations were compared between genetic cohorts. We also explored associations between age and TT, SHBG, FT and PCa, in the whole subset and stratified by BRCA1/2 PVs status. Results: A total of 777 participants in the IMPACT study had TT and SHBG measurements in serum samples at annual visits, giving 3940 prospective androgen levels, from 266 BRCA1 PVs carriers, 313 BRCA2 PVs carriers and 198 non-carriers. The median number of visits per patient was 5. There was no difference in TT, SHBG and FT between carriers and non-carriers. In a univariate analysis, androgen levels were not associated with PCa. In the analysis stratified by carrier status, no significant association was found between hormonal levels and PCa in non-carriers, BRCA1 or BRCA2 PVs carriers. Conclusions: Male BRCA1/2 PVs carriers have a similar androgen profile to non-carriers. Hormonal levels were not associated with PCa in men with and without BRCA1/2 PVs. Mechanisms related to the particularly aggressive phenotype of PCa in BRCA2 PVs carriers may therefore not be linked with circulating hormonal levels.
RESUMO
BACKGROUND: Septicemia plays an important role in neonatal morbidity and mortality, especially in developing countries. OBJECTIVE: To investigate the bacterial pathogens causing neonatal sepsis and their antibiotic susceptibility profile. METHODOLOGY: A total of 2,685 neonates aged 0-28 days were included in the study. Blood from each neonate was cultured and isolates were identified using standard biochemical tests. Antibiotic sensitivity pattern was analyzed using modified Kirby-Bauer disc diffusion method. RESULTS: Blood culture positivity was observed in 1,534 (57.1%) samples. Most of the cases (1089 counts - 71%) were of early onset sepsis while 445 (29%) were of late onset sepsis. The incidence of sepsis was higher in males 856 (55.8%) than females 678 (44.2%) with a 1:2 ratio. Similarly, 58.3% of septicemic patients were neonates with low birth weights. Twelve hundred and six (78.6%) isolates were gram negative while 328 (23.4%) were gram positive bacteria. E. coli was the dominant pathogen seen in 811 (52.8%) followed by Staphylococcus aureus 300 (19.5%), Pseudomonas 199 (13%), Klebsiella 102 (6.7%), Proteus 87 (5.7%), Staphylococcus epidermidis 28(1.8%) and Salmonella in 7 (0.5%) samples. All bacterial isolates showed high sensitivity to Imipenem, Enoxacin, Ofloxacin and Ciprofloxacin while low sensitivity was observed for other antibiotics (n = 16). The Proteus species showed high level of multiple resistances to all antibiotics (5.9%). CONCLUSION: Imipenem, Enoxacin, Ofloxacin and Ciprofloxacin can be used as an effective antibiotic regimen for treatment of bacterial sepsis in neonates.