Methadone Dose Adjustments, Plasma R-Methadone Levels and Therapeutic Outcome of Heroin Users: A Randomized Clinical Trial.

AIMS: We aimed to improve the retention in treatment and therapeutic outcome of methadone maintenance treatment (MMT) patients by adjusting the oral methadone dose in order to reach a "target" plasma R-methadone level (80-250 ng/mL). METHODS: A multicenter randomized controlled trial was organized. RESULTS: The intention-to-treat statistical analysis showed that repeated dose adjustments performed in order to obtain therapeutic plasma R-methadone levels did not improve retention in treatment of heroin-dependent patients. However, patients having plasma methadone levels in the "target range" at the beginning of the study had a better retention in treatment than controls. Furthermore, patients succeeding in keeping plasma R-methadone target levels (per protocol analysis) remained in treatment and improved their social scores better than controls. -Conclusion: Although the primary endpoint of this study was not demonstrated, a post hoc and a per protocol analysis suggested that patients in MMT with plasma R-methadone concentrations in the target range have a better therapeutic outcome than controls.

Effects of epidural and systemic maternal analgesia in term infants: the NoPiL study.

The aim of the No Pain in Labour (NoPiL) study was to evaluate the stress and clinical outcome of infants vaginally born without maternal analgesia and after maternal epidural or systemic analgesia. We studied 120 healthy term infants, 41 in the no analgesia group, 38 in the epidural analgesia group, and 41 in the systemic analgesia group. Cortisol, beta-endorphin, oxidative stress markers (ie: total hydroperoxide (TH) and advanced oxidation protein products (AOPP)), interleukin-1beta (IL-1beta), and interleukin-8 (IL-8) cytokines were measured in arterial cord blood samples. Infants in the 3 groups had similar Apgar score, cord blood pH and occurrence of hypoglycaemia, hyperbilirubinemia, and respiratory depression. Cortisol and endorphin plasma levels did not differ in the groups, nor did TH and AOPP values. IL-1beta and IL-8 cytokine were higher in infants born after maternal epidural analgesia than in other groups. Short-term outcome and stress were similar in infants vaginally born without maternal analgesia and after epidural and systemic analgesia. The possible implications of the highest interleukin levels in the epidural analgesia group deserve further study.

Experimentally-induced acute lung injury: the protective effect of hydroxyethyl starch.

The objective of this study was to evaluate the effects of hydroxyethyl starch, (130/0.4) 6%, compared to Ringer's acetate and modified gelatin on hypoxemia, inflammatory response, and oxidative stress in an experimental model of acute lung injury (ALI). The ALI/Adult Respiratory Distress Syndrome (ARDS) experimental model was produced by a bronchoalveolar saline lavage. Mature New Zealand white rabbits were anesthetized, provided with a tracheostomy and vascular catheters, and randomized to receive 25 ml/kg/hr of Ringer's acetate (group R, n = 7), 25 ml/kg/hr of modified gelatin (group G, n = 7), or 25 ml/kg/hr of hydroxyethyl starch (group S, n = 7). All of the rabbits received mechanical ventilation to maintain the PaCO2 between 35 and 45 mm Hg. Blood gas levels and hemodynamic values were recorded before induction of lung injury (T0) and 10 (T10), 120 (T120) and 240 (T240) min following induction of lung injury. At the same time-points, blood samples were collected to measure the plasma levels of TNFalpha (tumor necrosis factor-alpha) and TBARS (thiobarbituric acid-reactive substances). The experiment yielded the following results: The blood PaO2/FiO2 ratio was higher in group S than in groups R and G at T10, T120, and T240 (p <0.05). In group S, the plasma TNFalpha and TBARS concentrations were lower than in groups R and G at T120 and T240 (p <0.05). In conclusion, rabbits treated with hydroxyethyl starch, (130/0.4) 6%, demonstrated reductions of hypoxemia, inflammatory response, and oxidative lung damage, compared to raabbits treated with Ringer's acetate or modified gelatin.

Breast-feeding in a woman with cystic fibrosis undergoing antibiotic intravenous treatment.

We report the case of a 30-year-old woman with cystic fibrosis (CF) chronically infected with Pseudomonas aeruginosa who delivered and breast-fed a healthy boy. While breast-feeding the woman had to undergo an i.v. antibiotic course with tobramycin, due to pulmonary exacerbation. Tobramycin was not detected in her milk and lactation could be continued. This is the first time that the presence of tobramycin in the milk of a CF woman during i.v. administration has been investigated.

Role of heme oxygenase and bilirubin in oxidative stress in preterm infants.

In a previous study, it was found that the decrease in the total plasma bilirubin level (Btot) in preterm infants was associated with the decrease in oxidative stress. We hypothesized that this occurs as a result of a pro-oxidant effect of heme oxygenase (HO), which outcompetes with the antioxidant properties of bilirubin. In this study we studied 12 preterm infants in whom the plasma levels of Btot, total hydroperoxide (TH), protein SH groups, HO activity, non-transferrin-bound iron (NTBI), and erythrocyte CuZn superoxide dismutase (CuZn SOD) activity were concurrently measured when the Btot was >220 microM and after a Btot drop of >34 microM. The Btot decrease was concurrent with the TH decrease, protein SH groups increase, and the HO and CuZn SOD activity increase and was not associated with an NTBI increase. We concluded that 1) Btot does not exert a meaningful antioxidant effect in vivo; 2) HO does not exert a pro-oxidant effect involving an NTBI increase and that, on the contrary, it could exert an antioxidant effect; and 3) the concurrent HO and CuZn SOD activity increase could indicate a synergic antioxidant effect of the two enzymes.