Central nervous system penetration of oxycodone after intravenous and epidural administration.

BACKGROUND: Despite being increasingly used for pain management, only two studies, with controversial results, have evaluated the epidural use of oxycodone. METHODS: Twenty-four women, aged 26-64 yr, undergoing elective gynaecological surgery were enrolled in this randomized, double-blinded, parallel group study. The subjects were administered either i.v. oxycodone and epidural placebo (IV group; n=12) or epidural oxycodone and i.v. placebo (EPI group; n=12) after operation. Oxycodone was administered as a single dose of 0.1 mg kg(-1). An epidural catheter for drug administration was placed at T12/L1 and a spinal catheter for cerebrospinal fluid (CSF) sampling at L3/4. Plasma and CSF were frequently collected for the analysis of oxycodone and its major metabolites. The primary outcomes were the peak concentration (C(max)), time to peak concentration (T(max)), and the exposure (AUC(last)) of oxycodone in CSF and plasma. The secondary outcome was the analgesic efficacy, measured as the total dose of rescue fentanyl during the first four postoperative hours. RESULTS: In the EPI group, the median oxycodone Cmax and AUC(last) in the CSF were 320- and 120-fold higher, respectively, compared with the IV group. The total dose of rescue fentanyl was significantly lower in the EPI group (seven subjects needed 16 doses) than in the IV group [12 subjects needed 71 doses (P=0.001)]. No serious or unexpected adverse events were reported. CONCLUSIONS: Epidural oxycodone provides much higher CSF concentrations and possibly better analgesic efficacy than does i.v. oxycodone. CLINICAL TRIAL REGISTRATION: EudraCT reference number: 2011-000125-76.

The effects of pre- and post-pregnancy inflammatory bowel disease diagnosis on birth outcomes.

BACKGROUND: Inflammatory bowel diseases are frequent in women at their optimum age for reproduction. Possible effects on pregnancy are therefore of interest. AIM: To assess pregnancy outcomes in 212 women: 135 of whom were diagnosed with inflammatory bowel disease before pregnancy and 77 after pregnancy. METHODS: A clinical birth database was examined retrospectively. Odds ratios (ORs) for the main outcomes were calculated with 95% confidence intervals; these were adjusted for confounding factors. RESULTS: Overall, pregnancy outcomes were good. No increased risk of preterm births or need for neonatal intensive care was observed. However, women with inflammatory bowel disease had more growth-retarded newborns, at an adjusted OR of 2.08 (1.26-3.44) and the mode of delivery was more frequently Caesarean section, with an OR of 2.75 (1.82-4.16). In the women who were diagnosed with inflammatory bowel disease after the pregnancy, we found no difference in the obstetric outcome as compared with the general obstetric population. CONCLUSIONS: Most women with inflammatory bowel disease have a normal pregnancy outcome and, overall, inflammatory bowel disease during pregnancy poses low-to-moderate risks, the main concern being increased risk of impaired foetal growth. Normal maternal weight gain during pregnancy, possibly indicating a more stable disease, appeared to protect against adverse outcomes.

Alternative reproductive tactics and the propensity of hybridization.

One explanation for hybridization between species is the fitness benefits it occasionally confers to the hybridizing individuals. This explanation is possible in species that have evolved alternative male reproductive tactics: individuals with inferior tactics might be more prone to hybridization provided it increases their reproductive success and fitness. Here we experimentally tested whether the propensity of hybridization in the wild depends on male reproductive tactic in Calopteryx splendens damselflies. Counter to our expectation, it was males adopting the superior reproductive tactic (territoriality) that had greatest propensity to hybridize than males adopting the inferior tactics (sneakers and floaters). Moreover, among the territorial males, the most ornamented males had greatest propensity to hybridize whereas the pattern was reversed in the sneaker males. Our results suggest that there is fluctuating selection on male mate discrimination against heterospecific females depending on both ornament size and the male's reproductive tactic.