TP53 mutations in breast cancer tumors of patients from Rio de Janeiro,Brazil: association with risk factors and tumor characteristics

Somatic mutations in the TP53 gene are the most frequently observed genetic alterations in human malignancies, including breast cancer, which is one of the leading causes of death among women in Brazil. In our study, we determined the frequency and the pattern of TP53 mutations in malignant breast tumors from 120 patients living in Rio de Janeiro, Brazil. TP53 mutations were found in 20% of the tumors, which contained a diversity of mutation types: missense (62.5%), nonsense (8.3%), silent (4.2%), intronic (12.5%), insertion (4.2%) and deletion (8.3%). Of a total of 15 missense mutations, 4 were observed at Arg248 and 2 at Cys242, which are directly involved in DNA binding and in zinc binding, respectively. A subgroup of 51 patients was analyzed with respect to the relation between the presence of TP53 mutations and classical risk factors and with tumor and patient characteristics. For this analysis, we used logistic regression and, in order to obtain more precise confidence intervals, they were recalculated using a bootstrap resampling technique. Our results demonstrate that these mutations are not statistically associated with the risk factors or the patients' characteristics. However, the presence of TP53 mutations is strongly associated with the aggressiveness of the tumors, measured by Elston classification (OR = 11.97 and 95% CI of 2.24-307.05). This finding is in agreement with previous studies, which report the presence of TP53 mutations in tumors with poor prognosis. This correlation between tumor aggressiveness and TP53 mutations could be a crucial variable for the treatment and prognosis of breast cancer.     

Practice MRI: Reducing the need for sedation and general anaesthesia in children undergoing MRI

The aim of this study was to evaluate the effectiveness of a practice magnetic resonance unit, in preparing children to undergo magnetic resonance procedures without general anaesthesia (GA) or sedation. The records of children who attended the practice MRI between February 2002 and April 2004 were retrospectively reviewed. Each record was assessed as to whether the child had passed or failed the practice MRI intervention. Those children who were considered to have passed and were proceeded to a clinical non‐GA MRI had the report of the clinical scan reviewed. If the scan had been reported as non‐diagnostic because of movement artefact it was classified as a failed scan, otherwise it was considered a pass. One hundred and thirty‐four children undertook a practice MRI (age range 4.1–16.1 years, median age 7.7 years, 47% boys) and 120/134 (90%) passed the practice session. In all, 117/120 (98%) subsequently had a clinical non‐GA MRI and 110/117 (94%) passed (median age 7.8 years, 47% boys). Preparation is a safe and effective method to reduce the need for sedation and GA in children undergoing a clinical MRI scan. It provides a positive medical experience for children, parents and staff, and results in cost savings for the hospital.     

Risk factors for death from meningococcal infection in Recife, Brazil

To determine the case fatality rate and risk factors for death in children with invasive meningococcal infection, 163 children admitted with meningococcal disease to the Instituto Materno Infantil de Pernambuco, a tertiary paediatric teaching hospital in Recife, Brazil, were included in this retrospective cohort study. Cases were categorised as meningitis, septicaemia and septicaemia with meningitis. Forty-six (28.2 per cent) children had meningitis alone, 88 (54 per cent) septicaemia and meningitis and 29 (17.8 per cent) only septicaemia. Four of the patients with meningitis died (8.7 per cent), compared to 31 out of the 88 (35.2 per cent) with septicaemia and meningitis and 18 of the 29 (62.1 per cent) with septicaemia alone (p < 0.001). Symptoms <24 h (AOR 3.8, 95 per cent CI 1.1-13.1), platelet count <100 000 mm(3) (AOR 13.8, 95 per cent CI 3.1-60.9) and acidosis (AOR 6.0, 95 per cent CI 1.7-21) were the significant risk factors for death. Invasive meningococcal infection has a high case-fatality rate in this tertiary centre in Recife, especially in the septic forms. The identification of risk factors for death could contribute to the early recognition of patients with higher risk on admission in a middle-income country population.     

A case of double alleles at three Y-STR loci: forensic implications

In a genetic study of unrelated donors from Bahia (Brazil), one sample contained a 16 Y-STR haplotype with double peaks at three loci: DYS389 II, DYS437 and DYS439. The son of the subject had the same haplotype as found in the father. This profile was compared with a similar case found in a paternity case investigation in Madrid (Spain) and a match was found for the full 16 Y-STR haplotype. Because these three loci are located within the AZFa segment, these results are in accordance with duplication of the AZFa region that includes also other Y-STRs currently used in forensic investigation, for example DYS389I and DYS438. This case attracts our attention in the forensic interpretation of Y-haplotype profiles, because multiple alleles at various loci do not indicate forcibly that the sample under analysis is a mixture.     

Role of the NO-cGMP pathway in the systemic antinociceptive effect of clonidine in rats and mice

The mechanism underlying the analgesic effect of clonidine, an alpha(2)-adrenoceptor agonist, remains uncertain. Activation of alpha(2)-adrenoceptor induces the release of nitric oxide (NO) from endothelial cells, which has led us to test the hypothesis that the observed antinociceptive effect induced by the systemic administration of clonidine depends on the NO-cGMP pathway. The possible involvement of an opioid link in the antinociceptive effect of clonidine was also evaluated. The antinociceptive effect induced by systemic administration (intravenous or intraperitoneal) of clonidine was evaluated using the rat paw formalin, mice tail-flick and writhing tests. Clonidine (3-120 microg/kg) induces a dose-dependent antinociceptive effect in the formalin, tail-flick and writhing tests. The antinociceptive effect of clonidine in a dose that had no sedative effect assessed by rota rod test, was significantly reduced by NO-synthase and guanylyl cyclase inhibition. The antinociceptive effect of morphine, but not clonidine, was inhibited by naloxone. Our current results suggest that the antinociceptive effect of systemic clonidine does not involve the opioid receptor and is modulated by the NO-cGMP pathway.     

In vitro screening for antiplasmodial activity of isoquinoline alkaloids from Brazilian plant species

In the search for new antimalarial agents, nine Brazilian plant species were selected, from the Annonaceae (6), Menispermaceae (2) and Siparunaceae (1) families naturally occurring at the cerrado and Atlantic rainforest regions, in order to investigate their in vitro antiplasmodial activity. The ethanol and the alkaloid extracts were tested against K1, chloroquine-resistant, and Palo Alto, chloroquine-sensitive, strains of Plasmodium falciparum. The majority of the alkaloid extracts were more active than the ethanol ones, with IC(50) ranging 0.3-8.2 microg/mL. The crude Guatteria australis alkaloids were the most active against K1 with an IC(50) = 0.3 microg/mL. The most promising total alkaloid fractions for further bioguided isolation are those with the IC(50) < or = 5 microg/mL: G. australis, Cissampelos ovalifolia and Duguetia lanceolata.     

Household survey of dengue infection in central Brazil: spatial point pattern analysis and risk factors assessment

Urban dengue fever is now considered a major public health threat in most American countries. A household survey was conducted in the city of Goiania in central Brazil in 2001 to assess prevalence of dengue infection and individual and area-based risk factors. Spatial point pattern analysis was performed using the dual Kernel method. A total of 1,610 households were surveyed; 1,585 individuals more than five years old had blood and data collected. Sera were tested for IgM/IgG antibodies by an enzyme-linked immunoassay. Area-based indicators derived from census data were linked to geocoded residential address. The seroprevalence of dengue was 29.5% and the estimate prevalence surface reached 50% in the outskirts areas. The risk of infection was significantly associated with older age (P < 0.01), low education (odds ratio [OR] = 3.45, 95% confidence interval [CI] = 1.82-6.55), and low income (OR = 1.32, 95% CI = 1.02-1.71) in multivariate analysis. This study highlighted the heterogeneity of dengue transmission within the city and can assist in spatial targeting control interventions.     

Infection due to extended-spectrum beta-lactamase-producing Salmonella enterica subsp. enterica serotype infantis in a neonatal unit

OBJECTIVE: To describe the investigation and control of an outbreak of extended-spectrum beta-lactamase producing Salmonella enterica subsp. enterica serotype Infantis in a neonatal unit in Brazil. METHODS: A case-control study for risk factors for Salmonella Infantis systemic infection, environmental cultures, and evaluation of staffing and overcrowding and an assessment of infection control practices were performed. RESULTS: During July 1998 to June 1999, 140 Salmonella Infantis culture-positive patients were identified in the neonatal unit. Presence of a peripheral intravascular catheter was identified as an independent risk factor (odds ratio = 4.98; 95% CI = 1.59-19.31; P =.01) and each 250-g increase in birth weight as a protective factor (odds ratio = 0.76; 95% CI = 0.57-0.95; P =.03). Hospital stay was significantly longer and costs higher in case patients than in control patients. Salmonella Infantis was isolated from multiple environmental sources. Neonatal unit personnel were observed to make several breaks in infection control practices. The unit was understaffed and overcrowded. Prompt case identification, cohorting of patients, enhanced staff hand hygiene, and environmental cleaning terminated the outbreak. CONCLUSIONS: Inadequate infection control practices, nursery overcrowding, and understaffing can have an adverse effect on patient morbidity, mortality rates, and hospital cost.