PHARMACOKINETICS OF PROPOFOL IN WOMEN UNDERGOING ELECTIVE CAESAREAN SECTION

We have compared the pharmacokinetics of a bolus induction doseof propofol 2 mg kg^–1 in 10 Chinese women undergoing electiveCaesarean section with those in six non-pregnant Chinese womenhaving laparoscopic sterilization. Blood propofol concentrationswere measured using high pressure liquid chromatography withfluorimetric detection. Pharmacokinetic data were analysed bya model independent method based on statistical moment theory.Data from the laparoscopy group also underwent compartmentalanalysis, which produced similar kinetic results. Non-compartmentalanalysis estimated that the women undergoing Caesarean sectionhad a similar elimination half-life (mean 81.27 (SD 18.87) min)and apparent volume of distribution at steady state (2.66 (0.63)litre kg^–1) as non-obstetric patients (99.45 (29.40) minand 3.36 (1.87) litre kg^–1). Clearance was more rapidin the Caesarean section group (39.32 (8.07) ml min^–1kg^–1 vs 29.40 (8.72) ml min^–1 kg^–1) (P <0.05). The increased total body clearance may result from bloodloss and delivery of the fetus and placenta at operation, althoughan increase in extrahepatic clearance is also possible ^*Department of Anaesthesia, North West Regional Health Authority,Manchester     

RESERVE ALBUMIN AND BILIRUBIN TOXICITY INDEX IN INFANT SERUM

ABSTRACT. Reserve albumin concentration (the concentration of albumin available for binding of unconjugated bilirubin) was determined in 95 sera from 76 subjects by dialysis with ¹⁴C-monoacetyl diamino diphenyl sulfone (MADDS). An index, I of bilirubin toxicity in the plasma was calculated for each subject, based on the bilirubin and reserve albumin concentrations, the affinity of bilirubin for serum albumin, and the pH-dependent solubility of bilirubin in the plasma. The values of reserve albumin and of I varied significantly with gestational age, clinical condition (whether sick or well), and serum bilirubin level. The value of reserve albumin was decreased and I was increased in association with clinical factors (e. g., hyperbilirubinemia, hypoxia, acidosis, or sepsis) recognized as increasing the risk for bilirubin encephalopathy. The lowest values of reserve albumin and the highest values of I were found in the least mature and sickest infants.     

Obstetric epidural analgesia with mixtures of bupivacaine, adrenaline and fentanyl

We performed a double-blind comparison of six solutions for epidural analgesia in 90 healthy Chinese women with uncomplicated pregnancies. Patients were randomly allocated to receive 10 ml bupivacaine 0.125% or 0.25% plain, bupivacaine 0.125% with adrenaline 1.25 micrograms/ml, bupivacaine 0.25% with adrenaline 2.5 micrograms/ml or the latter two solutions with added fentanyl 50 micrograms. Analgesia was unsatisfactory in 30% of the bupivacaine 0.125% groups without fentanyl. The addition of adrenaline, compared with bupivacaine 0.25% plain, gave faster onset and longer duration of analgesia (p less than 0.05) which was similar to that found in both fentanyl groups. There were no differences in method of delivery or neonatal Apgar scores among groups. The least concentrated mixture that gave the best analgesia was the combination of bupivacaine 0.125% with adrenaline 1.25 micrograms/ml and fentanyl 50 micrograms.     

Serum interleukin-1 receptor antagonist is an early indicator of colitis onset in Gαi2-deficient mice

AIM: To study the serum concentration of IL-1β, IL-1 receptor antagonist (IL-1Ra) and IL-18 in Gαi2-deficient mice at the age of 6 (healthy), 12 (pre-colitic) and 24 wk (colitic) and in healthy control mice.METHODS: At the time of killing, serum samples were collected and IL-1β, IL-1Ra and IL-18 levels were measured using enzyme-linked immunosorbent assays.RESULTS: Serum concentration of IL-1Ra was significantly increased in pre-colitic (median: 524 ng/L;P=0.02) and colitic (450 ng/L; P=0.01), but not in healthy (196 ng/L) Gαi2-deficient mice as compared with controls (217 ng/L). Serum concentrations of IL-1β did not differ between Gαi2-deficient mice and their controls,irrespective of age, IL-18 was significantly increased in colitic, but not in pre-colitic mice compared with controls (510 ng/L vs 190 ng/L; P= 0.05).CONCLUSION: The increased serum concentrations of IL-18 and IL-1Ra in established diseases are suggested as markers of ongoing colitis. Interestingly, the significantly increased serum concentration of IL-1Ra in pre-colitic mice is found to be an early marker of disease progression.     

Altered risk‐aversion and risk‐taking behaviour in patients with Alzheimer's disease

Aim: Normal individuals are risk averse for decisions framed as gains but risk taking for decisions framed as losses. This framing effect is supposed to be attenuated in Alzheimer's disease (AD) patients. We investigated the effects of highlighting rewards versus highlighting punishments on the risky decision‐making of AD patients. Method: Fourteen mild to moderate AD patients (Mini‐Mental Status Examination score, 11–23; Clinical Dementia Rating, 1–2) and 16 healthy volunteers were recruited for the study. Subjects completed a computerized task on risky decision‐making in which mathematically equivalent dilemmas were presented in terms of opportunities to gain monetary rewards (‘positive frame’) or avoid suffering losses (‘negative frame’). Results: As expected, AD patients chose more risky options under the positive frame than the negative frame, contrary to the control group (Z =?2.671, P= 0.007). The normal difference in the distribution of risky choices between positively and negatively framed dilemmas was significantly reduced in the AD group after we adjusted for years of education, mean age and depression (F= 5.321, P= 0.030). Deliberation time did not differ significantly between the two groups. Conclusion: These results suggest that AD patients making high‐risk choices is associated with attenuated sensitivity to the emotional frames that highlight rewards or punishments, possibly reflecting altered evaluations of prospective gains and losses.     

Continuous intrathecal baclofen therapy in children with cerebral palsy – when does improvement emerge?

Aim: The aim of the study was to explore the timing of effects of intrathecal baclofen therapy in children with cerebral palsy. Methods: Thirty five children with severe disabilities with cerebral palsy who started continuous intrathecal baclofen therapy (CITB) were followed for 18 months. Pain, number of awakenings during night, spasticity, GMFM‐66 scores and PEDI scores were recorded the day before pump implantation and after 6 and 18 months of treatment respectively. Results: Introduction of CITB was associated with changes across all ICF dimensions. Reduced pain and improved sleep occurred within 6 months of treatment. Social function improved within 6 months and continued to improve until 18 months of CITB. Mobility also improved, but with a latency. Conclusion: There seems to be a sequence of changes after introduction of continuous intrathecal baclofen in a child with cerebral palsy that may guide the multidisciplinary team in their timing of therapy during post‐surgical follow‐up.     

Inhibition of Sanggenon G Isolated from Morus alba on the Metastasis of Cancer Cell

Objective An organic layer prepared from the cortex of Morus alba(Moraceae)was studied in order to identify the active compounds for heparinase.Methods Bioassay-guided fractionation resulted in the isolation of sanggenon G.Results The compound showed inhibitory activity with IC50 of 3.7μmol/L on heparinase in vitro as well as 24μmol/L in invasion assay using MDA-MB231 cells.Sanggenon G also had the moderate cytotoxicity at SW 620(colon)and ACHN(kidney)cancer cell lines with IC50 of 10.96 and 13.44μmol/L,respectively.Conclusion This is the first time that prenylated flavonoid sanggenon G is described as heparinase inhibitor.Besides,this flavonoid would be expected to be a metastasis inhibitor of cancer cells and also a valuable reagent to explore the mechanism of heparinase/heparanase-mediated metastasis.     

Titrated propofol induction vs. continuous infusion in children undergoing magnetic resonance imaging

Background: Propofol is the popular intravenous (i.v.) anaesthetic for paediatric sedation because of its rapid onset and recovery. We compared the efficacy and safety of a single dose and conventional infusion of propofol for sedation in children who underwent magnetic resonance imaging (MRI). Methods: This was a double‐blind, randomized‐controlled study. One hundred and sixty children were assigned to group I (single dose) or II (infusion). Sedation was induced with i.v. propofol 2 mg/kg, and supplemental doses of propofol 0.5 mg/kg were administered until adequate sedation was achieved. After the induction of sedation, we treated patients with a continuous infusion of normal saline at a rate of 0.3 ml/kg/h in group I and the same volume of propofol in group II. In case of inadequate sedation, additional propofol 0.5 mg/kg was administered and the infusion rate was increased by 0.05 ml/kg/h. Induction time, sedation time, recovery time, additional sedation and adverse events were recorded. Results: Recovery time was significantly shorter in group I compared with group II [0 (0–3) vs. 1 (0–3), respectively, P<0.001]. Group I (single dose) had significantly more patients with recovery time 0 compared with group II (infusion) (65/80 vs. 36/80, respectively, P<0.001). Induction and sedation times were not significantly different between groups. There was no significant difference in the frequency of additional sedation and adverse events between groups. Conclusion: A single dose of propofol without a continuous infusion can provide appropriate sedation in children undergoing MRI for <30 min.