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- Role of the RAD51 G172T polymorphism in the clinical outcome of cervical cancer patients under concomitant chemoradiotherapyPublication . Nogueira, A; Catarino, R; Faustino, I; Nogueira-Silva, C; Figueiredo, T; Lombo, L; Hilário-Silva, I; Pereira, D; Medeiros, RINTRODUCTION: Cervical cancer is one of the most common cancers diagnosed in women worldwide. Mammalian cells are constantly exposed to a wide variety of genotoxic agents from both endogenous and exogenous sources. The RAD51 protein is required for meiotic and mitotic recombination and plays a central role in homology-dependent recombinational repair of double-strand breaks (DSBs). Given the functional relevance of the DNA repair system on carcinogenesis, potential associations between genetic polymorphisms of DNA repair genes, cancer risk and response to therapy have been intensively evaluated. This is the first study evaluating the role of the RAD51 G172T genetic variants in cancer prognosis and clinical outcome of cervical cancer patients. MATERIAL AND METHODS: We analyzed RAD51 G172T polymorphism genotypes in cervical cancer patients who underwent a platinum-based chemotherapy in combination with radiotherapy. Genotyping was performed by Taqman™ Allelic Discrimination methodology. RESULTS AND DISCUSSION: Concerning the overall survival rates found using Kaplan-Meier method and Log Rank Test, we observed that the mean survival rates were statistically different according to the patients RAD51 genotypes. The group of patients carrying the T allele present a higher mean survival rate than the other patients (102.3months vs. 86.4months, P=0.020). Using the Cox regression analysis, we found an increased overall survival time for T-carrier patients, when compared with GG genotype, with tumor stage, age and presence of lymph nodes as covariates [hazard ratio (HR), 0.373; 95% CI, 0.181-0.770; P=0.008]. Among patients (n=193), RAD51 genotype frequency distributions were not under the influence of clinicopathologic characteristics, namely, treatment response (P=0.508), recurrence (P=0.150) and tumor stage (P=0.250). CONCLUSIONS: This is the first study evaluating the role of the RAD51 G172T genetic variants in cancer prognosis and clinical outcome of cervical cancer patients. Our results indicate an influence of the RAD51 genetic variants in overall survival of cervical cancer. Thereby, RAD51 G172T genotypes may provide additional prognostic information in cervical cancer patients who underwent cisplatin-based chemotherapy in combination with radiotherapy.
- Cortical maturation in fetuses referred for ‘isolated’ mild ventriculomegaly: a longitudinal ultrasound assessmentPublication . Miguelote, RF; Vides, B; Santos, RF; Palha, JA; Matias, A; Sousa, NOBJECTIVES: To compare cortical maturation between fetuses with isolated mild ventriculomegaly (IMV) and healthy fetuses, and to explore its potential prognostic value in IMV. METHODS: This prospective study quantified cortical maturation by ultrasound in 24 fetuses with IMV and 46 healthy fetuses. Depth and grading the developmental pattern of the parieto-occipital fissure (POF), calcarine fissure (CF) and sylvian fissure, and grading the Sylvian fissure operculization at 23-25, 27-28 and 31-32 weeks gestation were determined. RESULTS: At 23-25 and 27-28 gestational weeks, POF and CF mean depths were statistically lower in the IMV group. The POF and CF depth distribution had a normal distribution in the control group but displayed a bimodal distribution in the IMV group. IMV with progression of ventricular dilatation showed mean depth of CF lower than IMV in which ventriculomegaly regressed or remained stable. The sensitivity, specificity, positive predictive value and negative predictive value of a CF depth below the fifth percentile to predict progression of ventricular dilatation were, at 28 weeks, 100%, 88%, 67% and 100%, respectively. CONCLUSIONS: Cortical fissure assessment by ultrasound allowed the differentiation of a subgroup of IMV fetuses with a higher risk of progression of ventricular dilatation.
- Determinantes da colonização materna e da infecção neonatal por Streptococcus do grupo BPublication . Areal, A; Moreira, M; Nunes, S; Faustino, MA; Cardoso, L; Sá, CAim and Objective: During the past three decades, group B Streptococcus (GBS) neonatal infection has been the subject of little research. The aim of this study was to evaluate the association between maternal risk factors, as established by the Center for Disease Control and Prevention (CDC), and maternal colonization. We also analysed the association between risk factors present in newborns and early-onset GBS disease. Study design: Cross-sectional study. Population: All pregnant women admitted for delivery in our institution and their newborns, between 1st February and 31st July 2005. Methods: Maternal and neonatal characteristics were collected from hospital clinical data, including information on risk factors established by the CDC. Descriptive statistics was used to characterize the study sample. Qui-square and Mantel-haenszel tests were applied to compare proportions and to measure the strength of associations, respectively, setting significance at p < 0,05. Results: In this sample only 47% of women were screened for GBS colonization in suitable time and 34,9% of these women were colonized. The incidence of early neonatal infection by SGB was 9/1000 neonates. Significant associations between GBS maternal colonization ant the following parameters were observed: maternal age [p=0,012; OR=1,659 (IC a 95%, 1,218-2,260)], gestational age at labour [p=0,001; OR= 2,621 (IC a 95%, 1,641- 4,188)], and urinary GBS infection during pregnancy (p<0,001). Maternal colonization occurred in women without CDC defined risk factors. Early neonatal infection by SGB was strongly associated with unscreened women (p=0,014). Conclusion: In this study, maternal GBS colonization occurred in the absence of CDC defined risk factors and varied according to maternal age and gestational week. Neonatal GBS infection was more frequent in unscreened women.
- Risk Factors for Persistent Postsurgical Pain in Women Undergoing Hysterectomy Due to Benign Causes: A Prospective Predictive StudyPublication . Pinto, PR; McIntyre, T; Nogueira-Silva, C; Almeida, A; Araújo-Soares, VPersistent postsurgical pain (PPSP) is a major clinical problem with significant individual, social, and healthcare costs. The aim of this study was to examine the role of demographic, clinical, and psychological risk factors in the development of PPSP after hysterectomy due to benign disorders. In a prospective study, a consecutive sample of 186 women was assessed 24 hours before surgery (T1), 48 hours after surgery (T2), and 4 months after surgery (T3). Regression analyses were performed to identify predictors of PPSP. Four months after hysterectomy, 93 (50%) participants reported experiencing pain (numerical rating scale >0). Age, pain due to other causes, and type of hysterectomy emerged as significant predictive factors. Baseline presurgical psychological predictors identified were anxiety, emotional illness representation of the condition leading to surgery, and pain catastrophizing. Among the identified psychological predictors, emotional illness representation emerged as the strongest. Acute postsurgical pain frequency and postsurgical anxiety also revealed a predictive role in PPSP development. These results increase the knowledge on PPSP predictors and point healthcare professionals toward specific intervention targets such as anxiety (presurgical and postsurgical), pain catastrophizing, emotional illness representations, and acute pain control after surgery. PERSPECTIVE: This study found that presurgical anxiety, emotional illness representations, and pain catastrophizing are risk factors for PPSP 4 months after hysterectomy, over and above age and clinical variables. These findings improve knowledge on PPSP and highlight potential intervention targets for healthcare professionals.
- Thermal skin reference values in healthy late pregnancyPublication . Simões, R; Vardasca, R; Nogueira-Silva, CDigital thermal imaging has been employed in medicine for over 50 years. However, its use has been focused on vascular, musculoskeletal and neurological conditions, while other potential applications, such as obstetrics, have been much less explored. This paper presents a study conducted during 2011 at the Hospital of Braga on a group of healthy pregnant women in the last third of gestation. The analysis focused on characterizing typical pregnant women steady temperature profiles in specific defined regions of interest (ROI), and determining if the thermal symmetry values for late pregnant healthy women are in line with the values for non-pregnant healthy women. A temperature distribution pattern was found in the defined ROI. The obtained thermal symmetry value had a maximum of 0.3 +/- 0.2 degrees C, and there was no evidence for the influence of age (p > 0.05) in the observed group. The influence of the BMI requires further investigation since one ROI (P2 right) presented a p = 0.059, close to the threshold of statistical evidence in the influence of BMI. The study group presented symmetry values in line with non-pregnant reference values, but the profiles in temperature distribution are different. Assumptions can therefore now be used with higher confidence when assessing abnormalities in specific pathologic states during pregnancy using the defined ROI. This work represents a first contribution towards establishing guidelines for future research in this specific field of study.
- The impact of GGH -401C>T polymorphism on cisplatin-based chemoradiotherapy response and survival in cervical cancerPublication . Silva, IH; Nogueira-Silva, C; Figueiredo, T; Lombo, L; Faustino, I; Catarino, R; Nogueira, A; Pereira, D; Medeiros, RAIMS: Cervical cancer is the third most frequent cancer in women worldwide, mostly treated with cisplatin-based chemoradiotherapy. Since it is known that folate metabolism might interfere with cisplatin effectiveness, we intended to study the influence of the Gamma Glutamyl Hydrolase -401C>T polymorphism in treatment response in cervical cancer. METHODS: We retrospectively reviewed the clinical data of 167 patients with bulky cervical cancer submitted to cisplatin-based chemoradiotherapy. The genotypes of GGH -401C>T SNP were determined by real-time PCR and statistical analysis was performed by χ(2) test and survival analysis. RESULTS: The genotypes of GGH-401C>T were significantly associated with the response to platinum-based chemoradiotherapy. Treatment response was higher in patients carrying the CC genotype, who presented a significant increased chance of treatment response (survival time in months/genotype: 91 for CC Vs 72 for CT/TT; p=0.035, log rank test). A Cox regression analysis accordingly showed that the presence of the T allele was significantly linked to a worse treatment response (HR=3.036; CI 95% 1.032-8.934, p=0.044). CONCLUSIONS: The results of our study suggested the potential interest of GGH -401C>T as a predictive factor of the outcome of cervical carcinoma treated with cisplatin-based chemoradiotherapy.
- The role of glycoprotein 130 family of cytokines in fetal rat lung developmentPublication . Nogueira-Silva, C; Piairo, P; Carvalho-Dias, E; Veiga, C; Moura, RS; Correia-Pinto, JThe glycoprotein 130 (gp130) dependent family of cytokines comprises interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), cardiotrophin-like cytokine (CLC), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1) and oncostatin M (OSM). These cytokines share the membrane gp130 as a common signal transducer. Recently, it was demonstrated that IL-6 promotes, whereas LIF inhibits fetal lung branching. Thus, in this study, the effects on fetal lung morphogenesis of the other classical members of the gp130-type cytokines (IL-11, CLC, CNTF, CT-1 and OSM) were investigated. We also provide the first description of these cytokines and their common gp130 receptor protein expression patterns during rat lung development. Fetal rat lung explants were cultured in vitro with increasing concentrations of IL-11, CLC, CNTF, CT-1 and OSM. Treated lung explants were morphometrically analyzed and assessed for MAPK, PI3K/AKT and STAT3 signaling modifications. IL-11, which similarly to IL-6 acts through a gp130 homodimer receptor, significantly stimulated lung growth via p38 phosphorylation. On the other hand, CLC, CNTF, CT-1 and OSM, whose receptors are gp130 heterodimers, inhibited lung growth acting in different signal-transducing pathways. Thus, the present study demonstrated that although cytokines of the gp130 family share a common signal transducer, there are specific biological activities for each cytokine on lung development. Indeed, cytokine signaling through gp130 homodimers stimulate, whereas cytokine signaling through gp130 heterodimers inhibit lung branching.
- Disfunção sexual feminina em idade reprodutiva: prevalência e factores associadosPublication . Ribeiro, B; Magalhães, AT; Mota, IObjetivos: A disfunção sexual feminina (DSF) é altamente prevalente, situando-se entre os 40% e 70% em Portugal, e traduz-se por uma alteração em qualquer uma das fases do ciclo de resposta sexual da mulher (desejo, excitação e orgasmo) ou ainda por perturbações dolorosas associadas ao ato sexual. O presente estudo pretendeu estudar a prevalência da DSF numa amostra de mulheres em idade reprodutiva, a prevalência dos diferentes subtipos de DSF e a existência de fatores associados. Tipo de estudo: Tratou-se de um estudo observacional, transversal e analítico. Local: Unidades de Saúde Familiar (USF) Novo Cuidar, Centro de Saúde de Fafe. População: Mulheres entre os 18 e os 58 anos utentes da USF Novo Cuidar. Métodos:A uma amostra aleatória de 346 utentes foi aplicado um questionário anónimo e confidencial de autorresposta. Usaram-se os testes Qui-Quadrado ou de Fisher para comparar proporções, o Odds Ratio para determinar a força de associação entre variáveis e os testes t-Student e Mann-Whitney para testar a associação entre variáveis qualitativas e quantitativas (adotou-se um nível de significância de 0,05). Resultados: A taxa de resposta foi de 86,4% e a prevalência de DSF foi de 77,2% (IC95% 72,0-82,7), tendo a perturbação do orgasmo sido o subtipo mais prevalente, 55,8% (IC95% 51,0-63,9). Foi encontrada uma associação entre a contraceção hormonal e a perturbação do desejo (p = 0,003). A aversão sexual foi estatisticamente relacionada com experiências sexuais indesejadas prévias (p = 0,001). Conclusões: A DSF em idade reprodutiva é muito prevalente apesar de apenas metade das mulheres a considerarem um problema. Foram encontradas associações com alguns fatores que podem ter importância na vivência de uma sexualidade feliz pela mulher.
- The impact of GGH -401C>T polymorphism on cisplatin-based chemoradiotherapy response and survival in cervical cancerPublication . Silva, IH; Nogueira-Silva, C; Figueiredo, T; Lombo, L; Faustino, I; Catarino, R; Nogueira, A; Nogueira, D; Medeiros, RAIMS: Cervical cancer is the third most frequent cancer in women worldwide, mostly treated with cisplatin-based chemoradiotherapy. Since it is known that folate metabolism might interfere with cisplatin effectiveness, we intended to study the influence of the Gamma Glutamyl Hydrolase -401C>T polymorphism in treatment response in cervical cancer. METHODS: We retrospectively reviewed the clinical data of 167 patients with bulky cervical cancer submitted to cisplatin-based chemoradiotherapy. The genotypes of GGH -401C>T SNP were determined by real-time PCR and statistical analysis was performed by χ(2) test and survival analysis. RESULTS: The genotypes of GGH-401C>T were significantly associated with the response to platinum-based chemoradiotherapy. Treatmentresponse was higher in patients carrying the CC genotype, who presented a significant increased chance of treatment response (survival time in months/genotype: 91 for CC Vs 72 for CT/TT; p=0.035, log rank test). A Cox regression analysis accordingly showed that the presence of the T allele was significantly linked to a worse treatment response (HR=3.036; CI 95% 1.032-8.934, p=0.044). CONCLUSIONS: The results of our study suggested the potential interest of GGH -401C>T as a predictive factor of the outcome of cervical carcinoma treated with cisplatin-based chemoradiotherapy.
- A infecção peri-natal por Streptococcus agalactiae pode ser evitada: prevalência da colonização em parturientes no Hospital de S. Marcos, factores de risco e sua relação com a infecção peri-natalPublication . Areal, A; Nunes, S; Moreira, M; Faustino, MA; Cardoso, L; Sá, Cntrodução: O Streptococcus agalactiae (SGB) é o agente mais frequente de infecção neonatal precoce, sendo possível a sua prevenção. Em Portugal é desconhecida a prevalência de mulheres colonizadas por SGB. O estudo da Unidade de Vigilância Pediátrica refere uma prevalência nacional de infecção neonatal por SGB de 0,5:1000 nados-vivos. Objectivo: Determinar a prevalência da colonização materna e da infecção perinatal por SGB no Hospital de S. Marcos, Braga (HSM), de modo a avaliar a importância da implementação do rastreio universal e o uso de medidas profiláticas. Método: De 1 de fevereiro a 31 de julho de 2005 foi realizado um estudo transversal com análise de coortes anichada, avaliando todas as grávidas assistidas para trabalho de parto no HSM e respectivos recém-nascidos. Os dados foram submetidos a análise estatística bi-variada pelo teste do qui-quadrado, com um nível de significância de 5% (p<0,05). Resultados: A prevalência da colonização nas grávidas rastreadas na região de Braga foi de 34,9 % [intervalo de confiança a 95% (IC95%), 31,5-38,3%]. No HSM o diagnóstico de infecção neonatal precoce por SGB ocorreu em 9:1000 recém-nascidos. O risco relativo de ocorrência de infecção perinatal entre os recém-nascidos dos grupos de mães rastreadas e não rastreadas foi de 0,3 [IC95% 0,2,7-0,32]. Conclusão: O rastreio bacteriológico positivo para colonização materna por SGB associado à adequada profilaxia intra-parto reduziu significativamente a infecção neonatal precoce, em relação ao grupo de gestantes não rastreadas (p=0,014). Consideramos que é recomendável a instituição do rastreio universal das grávidas e a profilaxia adequada quando indicada.