Fluconazole prophylaxis in extremely low birth weight infants and neurodevelopmental outcomes and quality of life at 8 to 10 years of age.

OBJECTIVE: To examine the long-term effects of fluconazole prophylaxis in extremely low birth weight infants. STUDY DESIGN: Neurodevelopmental status and quality of life of survivors from a randomized, placebo-controlled trial of fluconazole prophylaxis were evaluated at 8 to 10 years of life using the Vineland Adaptive Behavior Scales-II (VABS-II) and the Child Health Questionnaire Parent-Completed Form 28 (CHQ-PF28), respectively. RESULTS: VABS-II Domain Scores for the fluconazole-treated (n = 21; 9.1 ± 0.7 years) compared with the placebo group (n = 17; 9.3 ± 0.8 years) were similar for communication [94.6 (±14.8) versus 92.6 (±12.6), P = .65], daily living skills [87.9 (±10.6) versus 87.4 (±9.3), P = .89], socialization [97.2 (±9.2) versus 94.4 (±7.9), P = .31], and motor skills [92.1 (±17.8) versus 95.1 (±14.6), P = .57]. Internalizing and externalizing behaviors and maladaptive behavior index were also similar. The CHQ-PF28 revealed no differences between the two groups regarding quality of life. Survivors were also happy or satisfied with school (90% versus 100%, P = .49), friendships (90% versus 88%, P = 1.00), and life (95% versus 100%, P = 1.00). Self esteem scores were 87.3 ± 15.7 versus 89.7 ± 10.4 (P = .59). There were also no differences between groups regarding emotional difficulties or behavior problems. CONCLUSIONS: Fluconazole prophylaxis for the prevention of invasive Candida infections is safe in extremely low birth weight infants and does not appear to be associated with any long-term adverse effects on neurodevelopment and quality of life at 8 to 10 years of life.

Cytokine elaboration in critically ill infants with bacterial sepsis, necrotizing entercolitis, or sepsis syndrome: correlation with clinical parameters of inflammation and mortality.

OBJECTIVE: To test the hypothesis that cytokines might distinguish critically ill infants with bacterial sepsis or necrotizing enterocolitis (NEC) from those with sepsis syndrome and that these elevations would be correlated with clinical variables of inflammation and mortality. STUDY DESIGN: We measured plasma and tracheal aspirate (TA) levels of interleukin-8 (IL-8), epithelial neutrophil activating peptide (ENA-78), IL-10, and IL-18 in 84 neonates with suspected sepsis or NEC. Thirty-one infants had bacterial sepsis, 19 had NEC, and 34 infants with negative results on cultures had sepsis syndrome. RESULTS: Plasma IL-8 and IL-10 levels were significantly increased in infants with bacterial sepsis compared with those in infants with sepsis syndrome. Plasma IL-8, ENA-78, and IL-10 levels were elevated in infants with NEC compared with those in infants with sepsis syndrome. TA IL-8 and IL-10 levels were also increased in infants with bacterial sepsis; TA ENA-78, and IL-18 were not elevated in infants with sepsis or NEC when compared with infants with sepsis syndrome. Plasma and TA cytokine levels correlated with hematologic parameters. Plasma cytokine levels were higher in infants who did not survive than in infants who did survive. CONCLUSIONS: Plasma and TA cytokine levels are elevated in critically ill infants with bacterial sepsis or NEC compared with those in infants with sepsis syndrome. Our results suggest distinct patterns of cytokine elaboration in different disease states.

Twice weekly fluconazole prophylaxis for prevention of invasive Candida infection in high-risk infants of <1000 grams birth weight.

OBJECTIVES: We tested the hypothesis that twice weekly prophylactic dosing of fluconazole prevents invasive candidiasis without promoting resistant Candida species in high-risk, preterm infants. STUDY DESIGN: We compared our previous dosing schedule (Group A) to a less frequent dosing schedule of twice a week (Group B) of fluconazole prophylaxis for up to 6 weeks in a prospective, randomized, double-blind clinical trial in preterm infants weighing <1000 grams at birth and with an endotracheal tube and/or central vascular catheter over a 24-month period. Weekly surveillance cultures were obtained on study patients. RESULTS: Candida colonization was documented in 5 (12%) of 41 Group A and in 4 (10%) of 40 Group B infants. Candida sepsis developed in two (5%) of Group A and one (3%) of Group B infants (risk difference, -0.02; 95% confidence interval, -0.14-0.10; P=.68). All fungal isolates remained sensitive to fluconazole, and no drug side effects were documented. CONCLUSIONS: Twice weekly dosing of prophylactic fluconazole can decrease Candida colonization and invasive infection, cost, and patient exposure in high-risk, preterm infants weighing <1000 grams at birth. We speculate that lower and less frequent dosing may delay or prevent the emergence of antifungal resistance.

Aplastic anemia in Brazil: incidence and risk factors.

This study is the first large-scale epidemiological investigation of acquired aplastic anemia (AAA) in South America. The objective was to estimate the incidence and to identify risk factors for AAA in Brazil. A national case-control study was conducted to investigate the risk factors for the disease. One hundred twenty-five cases and 129 controls were included. Multiple logistic regression was used in the estimation of odds ratios (OR) to control confounding. The size of Brazil made it unfeasible to estimate the incidence of AAA in the whole country, and we limited the calculation to the state of Parana. The annual incidence of AAA in Parana was 2.4 cases/10(6) inhabitants. There was no positive association between chloramphenicol use and AAA (OR 0.4; 95% CI: 0.1-2.9). The OR of AAA associated with household pesticides that include organophosphates in their composition was 2.7 (1.0-8.4). The OR for the usage of unspecified thinner and/or acetone for at least 7 days was 3.0 (1.2-7.3). Cases of AAA in Brazil seem to be associated with some factors traditionally related to this disease, such as certain solvents and the incidence is similar to what has been reported from Europe.

LeIF A recombinant Leishmania protein that induces an IL-12-mediated Th1 cytokine profile

We have evaluated the ability of the Leishmania protein LeIF to influence the Th1/Th2 cytokine responses and the generation of LeIF-specific T cell clones in the absence of adjuvant. We characterized LeIF-specific T cell responses in Leishmania major. Infected and uninfected BALB/c mice. These mice develop a strong Th2 response during infection with L. major. When lymph node cells from infected BALB/c mice were stimulated in vitro with LeIF, only IFN-ã (and no detectable IL-4) was found in the culture supernatant. In addition, LeIF down-regulated Leishmania Ag-specific IL-4 production by lymph node cells from infected BALB/c mice. Subsequently, Th responses were evaluated in naive BALB/c mice following immunization with LeIF. T cell clones derived from mice immunized with LeIF preferentially secreted IFN-ã. Finally, to understand the basis for the preferential Th1 cytokine bias observed with LeIF, the ability of LeIF to influence the early cytokine profile was evaluated in splenocytes of SCID mice. We found that LeIF stimulated fresh spleen cells from naive SCID mice to secrete IFN-ã by IL-12/IL-18-dependent mechanisms. The N-terminal half of the molecule (amino acid residues 1-226) maintained the ability to stimulate IFN-ã from splenocytes of SCID mice. Finally, we also demonstrated that LeIF was able to provide partial protection of BALB/c mice against L. major. Thus, our results suggest the potential of LeIF as a Th1-type adjuvant and as a therapeutic and prophylactic vaccine Ag for leishmaniasis when used with other leishmanial Ags

Uso de estrogênio näo-anticoncepcional e risco de câncer mamário / The use of non anticonceptive estrogens and risk of breast neoplasms

A relaçäo entre o risco de câncer mamário e uso de estrogênios näo-anticoncepcionais foi investigada num estudo hospitalar em 1.610 mulheres com câncer mamário e 1.606 com outras condiçöes. A estimativa do risco relativo global para os estrogênios conjugados, tomados pela primeira vez 18 meses, pelo menos, antes da hospitalizaçäo, em comparaçäo com ausência de uso de quaisquer estrogênios näo-anticoncepcionais foi 0,9 (intervalo de confiança 95% - 0,7 a 1,1). Para outros estrogênios, tomados pelo menos 18 meses antes da hospitalizaçäo, a estimativa foi 0,8 (0,6 a 1,1). Quando levados em conta os fatores conhecidos de câncer mamário, os resultados foram semelhantes. Entre as mulheres pós-menopáusicas, os estrogênios conjugados näo pareceram aumentar o risco de câncer mamário, mesmo quando tomados por muitos anos, no passado distante. Näo houve prova de maior risco devido ao uso de estrogênios conjugados entre os subgrupos de mulheres definidos segundo os vários fatores de risco de câncer mamário. Os resultados deste estudo sugerem que os estrogênios näo anticoncepcionais näo aumentam o risco de câncer mamário