The effect of pre-eclampsia on the levels of coagulation and fibrinolysis factors in umbilical cord blood of newborns.

The effect of pre-eclampsia on coagulation and fibrinolysis in newborns is still under investigation. We have evaluated several coagulation and fibrinolysis parameters in umbilical cord blood of 20 newborns from pre-eclamptic women and of 40 newborns from normotensive women with similar gestational age. Additionally, the presence of factor V Leiden and prothrombin G20210A mutation in cord blood has been assessed. Neonates from pre-eclamptic women exhibited significantly lower birth weight (2.48 +/- 0.92 versus 2.88 +/- 0.68 kg, P < 0.05) and were more frequently admitted to the neonatal intensive care unit (45 versus 20%, P < 0.01) as compared with neonates from normotensive women. Cord blood protein C antigen and activated protein C resistance mean levels were slightly higher in the group of neonates from pre-eclamptic mothers. Fibrinogen levels were lower in this group as compared with control newborns (132.17 +/- 46.97 versus 156.08 +/- 49.58 mg%, P < 0.02), and unrelated to birth weight. No significant differences between cases and controls were found in plasminogen activator inhibitor-1 or tissue plasminogen activator cord blood levels. Heterozygous prothrombin 20210A was found in three newborns from normotensive mothers, whereas no factor V Leiden mutation was found in either group. In conclusion, pre-eclampsia seems to have only mild effects on coagulation and fibrinolytic factors in the cord blood of newborns. Since no excess of common polymorphisms predisposing to thrombosis was found in newborns from pre-eclamptic mothers, it is unlikely that the carriership status of these genetic defects of newborns influences the adverse pregnancy/neonatal outcomes.     

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin administered to pregnant rats during the preimplantation period

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was given by gavage to pregnant rats on the 1st–3rd days of gestation in dosages of 0 (control), 0.125, 0.5, and 2 μg/kg/day. The treatment did not increase pre- and postimplantation losses. Mean fetal weight was reduced at the 0.5 and 2 μg/kg dose levels.     

Effects of São Paulo air pollution on the upper airways of mice

The nose is the first region of the respiratory tract to come in contact with airborne pollutants. Previous studies have shown that the nasal mucosa can be altered in response to air pollution. In this study, we quantified neutral and acidic mucus in three different levels of the nasal cavity of mice exposed to ambient levels of air pollution in the city of S?o Paulo, Brazil. Two groups of 6-day-old male Swiss mice were placed in two exposure chambers. Mice were maintained in the chambers 24 h/day, 7 days/week for 5 months. The first chamber contained an air filter device (clean chamber; n=20), whereas the second one received ambient air pollution (polluted chamber; n=20). We measured the concentration of PM(2.5), nitrogen dioxide (NO2), and black carbon inside both chambers. The nasal cavity was transversely sectioned at three specific anatomic locations (proximal, medial, and distal levels) and submitted to quantitative analysis of the amounts of neutral and acidic mucosubstances. We observed a 37.85% decrease in NO2, 54.77% decrease in PM(2.5), and 100% decrease in black carbon concentration in the clean chamber compared to the polluted chamber. Significant differences between polluted and clean chambers were observed in the epithelium lining the septum of proximal and medial levels of the nasal mucosa, with an increase in the percentage of acidic mucus in the polluted chamber (P=0.037, proximal level; P=0.023, medial level). We conclude that prolonged exposure to low levels of ambient air pollution from an early age shows evidence of causing secretory changes in the nasal cavity of mice, with increased production of acidic mucosubstances.     

Gemcitabine and liposomal doxorubicin in the salvage treatment of ovarian cancer: updated results and long-term survival

OBJECTIVE: The combination of GEM/PLD has been tested for its efficacy on survival of recurrent ovarian cancer patients. METHODS: This is a multicenter phase II study of GEM/PLD regimen in recurrent ovarian cancer patients previously treated with at least one platinum/paclitaxel regimen, and with evidence of measurable disease. PLD, 30 mg m(-2), was administered on day 1 followed by GEM, 1000 mg m(-2), on days 1 and 8, every 21 days. RESULTS: 106 patients were available for response evaluation. 9 complete responses (8.5%) and 27 partial responses (25.5%) have been registered. 36 patients (34.0%) experienced stabilization of disease, while 34 (32.1%) cases progressed during treatment. OS was significantly shorter in platinum-resistant (median OS = 50 weeks) than in platinum-sensitive patients (median OS = 92 weeks) (P value = 0.0016). In the group of platinum-sensitive patients, cases responsive to GEM/PLD combination showed a better OS with respect to patients unresponsive to GEM/PLD (median OS = 120 weeks versus median OS = 60 weeks, P value = 0.019). The same trend was observed in platinum-resistant patients. Grade 4 hematological toxicity affected 20 patients (18%). Grade 3 palmar-plantar erythrodysesthesia (PPE) was registered in 16 patients (14.4%). Grades 3 and 4 mucositis was documented in 16 (14.4%) and 2 (1.8%) patients, respectively. CONCLUSIONS: GEM/PLD combination represents a valid approach in recurrent ovarian cancer patients. The hematological toxicity was easily managed, and the incidence and severity of PPE was low.     

Human epithelial growth factor receptor 2 (HER2) status in primary and metastatic esophagogastric junction adenocarcinomas

Differences in human epithelial growth factor receptor 2 dysregulation in primary solid tumors and metastases may (at least partially) explain human epithelial growth factor receptor 2-targeted therapeutic inconsistencies. Human epithelial growth factor receptor 2 status was tested in a series of 47 radically treated consecutive esophagogastric junction adenocarcinomas (male/female, 38/9; mean age, 67.9 years) in both primary cancers and paired synchronous nodal metastases. None of the patients received neoadjuvant therapy. For each case, 2 nonadjacent tissue samples from primary esophagogastric junction adenocarcinoma and 2 different metastatic nodes were considered (188 tissue samples in all). Human epithelial growth factor receptor 2 status was assessed by immunohistochemistry (PATHWAY-HER2/neu [4B5]; Ventana Medical Systems, Milan, Italy) and dual chromogenic in situ hybridization (duoCISH; DAKO, Glostrup, Denmark). Immunohistochemistry staining scores were nil in 22 tumors (47%), 1 (21%) in 10, 2 (13%) in 6, and 3 (19%) in 9. Human epithelial growth factor receptor 2 gene amplification (25.5%) was associated with more differentiated phenotype (Fisher exact test, P = .039) and advanced tumor stage (Fisher exact test, P = .015). Significant agreement was observed between human epithelial growth factor receptor 2 protein expression (immunohistochemistry) and human epithelial growth factor receptor 2 gene's amplification (chromogenic in situ hybridization) (κ = 0.84, P < .001). Both immunohistochemistry and chromogenic in situ hybridization documented an excellent intratumor agreement in human epithelial growth factor receptor 2 status (κ = 0.75, P < .001; κ = 0.88, P < .001, respectively). Human epithelial growth factor receptor 2 status was comparable in primary versus metastatic nodal cancers by both immunohistochemistry and chromogenic in situ hybridization (Cohen Φ, both P < .001). In esophagogastric junction adenocarcinomas, human epithelial growth factor receptor 2 status (as assessed by immunohistochemistry and/or chromogenic in situ hybridization) is virtually unaffected by intratumor variability; it is consistent with findings in nodal metastases, and it reliably identifies patients with esophagogastric junction adenocarcinoma eligible for anti-human epithelial growth factor receptor 2 therapy.