Giving phenylephrine alone by infusion at cesarean delivery was associated with a lower incidence of fetal acidosis and maternal nausea and vomiting than giving ephedrine alone. There was no advantage to combining phenylephrine and ephedrine because it increased nausea and vomiting, and it did not further improve fetal blood gas values, compared with giving phenylephrine alone.

Although 1p/19q codeletions define "genetically favorable" oligodendrogliomas, eventual tumor progression and patient death remain constant. Genetic testing is often performed at the time of recurrence, though it is unclear whether these or other genetic alterations provide useful prognostic information. We characterized 138 of 189 (73%) available primary and recurrent oligodendroglial neoplasms from 80 patients, utilizing paired FISH probes for 1p32/1q42, 19p13/19q13, CEP7/EGFR, CEP9/p16, and PTEN/DMBT1. Patients were followed until death (49%), or a median follow-up of 8.9 years. Patients with 1p/19q codeleted tumors (71%) had an estimated overall median survival of 14.9 years with an estimated 3.9 years from first recurrence. In contrast, those lacking deletions had significantly lower estimated overall median survivals of 4.7 years and 1.0 year after first recurrence (both p < 0.001). This increased survival in patients with 1p/19q codeleted tumors remained significant when adjustments were made for age, tumor grade, type of surgical procedure, and treatment with radiation or chemotherapy. Only 1 recurrence showed focal EGFR amplification, while 5 developed 10q deletions, mostly in high-grade mixed oligoastrocytomas lacking 1p/19q deletions. In contrast, p16 (9p21) deletions were common and associated with both high grade (p < 0.001) and recurrence (p = 0.002). Our data suggest that in classic oligodendrogliomas: 1) 1p/19q tumor status is a powerful predictor of patient survival, even after recurrence; 2) p16 deletions are common progression-associated alterations; and 3) 10q deletions and EGFR amplifications are sufficiently rare to suggest the possibility of alternate diagnoses.

BackgroundBisphenol A (BPA) is widely used in the manufacture of polycarbonate plastics, including infant formula bottles.ObjectivesBased on the reported endocrine disruptor activity of this polyphenol, we hypothesized that exposure to BPA early in life would elicit developmental changes in the mammary tissue and cause a predisposition for mammary cancer.MethodsWe exposed neonatal/prepubertal rats to BPA via lactation from nursing dams treated orally with 0, 25, and 250 μg BPA/kg body weight/day. For tumorigenesis studies, female offspring were exposed to 30 mg dimethylbenzanthracene (DMBA)/kg body weight at 50 days of age.ResultsThe combination of DMBA treatment with lactational exposure to BPA demonstrated a dose-dependent increase in mammary tumor multiplicity and reduced tumor latency compared with controls. In the absence of DMBA treatment, lactational BPA exposure resulted in increased cell proliferation and decreased apoptosis at 50 but not 21 days postpartum (shortly after last BPA treatment). Using Western blot analysis, we determined that steroid receptor coactivators (SRCs) 1–3, Akt, phosphorylated Akt, progesterone receptor A (PR-A), and erbB3 proteins were significantly up-regulated at 50 days of age.ConclusionsThe data presented here provide the first evidence that maternal exposure to BPA during lactation increases mammary carcinogenesis in a DMBA-induced model of rodent mammary cancer. Changes in PR-A, SRC 1–3, erbB3, and Akt activity are consistent with increased cell proliferation and decreased apoptosis playing a role in mammary cancer susceptibility. These alterations provide an explanation of enhanced mammary carcinogenesis after lactational BPA exposure.

Purpose: Dihydropyrimidine dehydrogenase (DPD)-deficient cancer patients have been shown to develop severe toxicity after administration of 5-fluorouracil. Routine determination of DPD activity is limited by time-consuming and labor-intensive methods. The purpose of this study was to develop a simple and rapid 2-13 C-uracil breath test, which could be applied in most clinical settings to detect DPDdeficient cancer patients.Experimental Design: Fifty-eight individuals (50 "normal," 7 partially, and 1 profoundly DPD-deficient) ingested an aqueous solution of 2-13 C-uracil (6 mg/kg). 13 CO 2 levels were determined in exhaled breath at various time intervals up to 180 min using IR spectroscopy (UBiT-IR 300 ). DPD enzyme activity and DPYD genotype were determined by radioassay and denaturing high-performance liquid chromatography, respectively.Results: The mean (؎SE) C max , T max , ␦ over baseline values at 50 min (DOB 50 ) and cumulative percentage of 13 C dose recovered (PDR) for normal, partially, and profoundly DPD-deficient individuals were 186.4 ؎ 3.9, 117.1 ؎ 9.8, and 3.6 DOB; 52 ؎ 2, 100 ؎ 18.4, and 120 min; 174.1 ؎ 4.6, 89.6 ؎ 11.6, and 0.9 DOB 50 ; and 53.8 ؎ 1.0, 36.9 ؎ 2.4, and <1 PDR, respectively. The differences between the normal and DPD-deficient individuals were highly significant (all Ps <0.001).Conclusions: We demonstrated statistically significant differences in the 2-13 C-uracil breath test indices (C max , T max , DOB 50 , and PDR) among healthy and DPDdeficient individuals. These data suggest that a single time-point determination (50 min) could rapidly identify DPD-deficient individuals with a less costly and timeconsuming method that is applicable for most hospitals or physicians' offices.

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