Anaesthesia for translumbar aortography

Fifty patients presenting for elective translumbar aortography were randomly allocated to one of two groups receiving either enflurane or isoflurane. Premedication was with oral lorazepam. The patients' tracheas were intubated and they were allowed to breathe spontaneously in the prone position during the procedure. There was no significant difference in heart rate during the investigation but there was a statistically significant fall in the blood pressure from its pre-induction level. Arterial oxygenation was adequate throughout the procedure. Arterial carbon dioxide tension was significantly lower in the isoflurane group at the beginning and at end of the procedure (p less than 0.01), but there was no significant change in carbon dioxide tension within the groups during the procedure. Spontaneous ventilation with enflurane or isoflurane is a satisfactory anaesthetic technique for translumbar aortography.     

Double-blind crossover study of the efficacy and acceptability of oxazepam Expidet tablets compared to placebo in patients undergoing gynaecological surgery

In a double-blind crossover trial, the hypnotic efficacy and acceptability of oxazepam Expidet, a fast-dissolving tablet, was compared to placebo in patients undergoing minor gynaecological surgery. Patients received 30 mg oxazepam Expidet or placebo the night before their operation and the alternate medication the night after. A sleep questionnaire was completed the morning after both nights and acceptability was assessed the morning after the second night. Data were available for analysis on seventy-two patients aged 18-50 years. There was a significant improvement in sleep onset and quality and less awakenings after oxazepam compared to placebo (p less than or equal to 0.01). There was no significant difference in the occurrence or type of dreams, or morning-after symptoms. There was a significant preference for oxazepam compared to placebo and for the fast-dissolving Expidet form compared to conventional tablets or capsules (p less than or equal to 0.01). There were no adverse reactions in the oxazepam group. It was concluded that oxazepam Expidet was an effective and acceptable hypnotic in this group of patients.     

Changes in ecdysteroid and juvenile hormone titers in the hemolymph of Galleria mellonella larvae and pupae

The variations in circulating ecdysteroids and juvenile hormones (JH) in Galleria, from the end of the antepenultimate larval stage until emergence of adults, have been determined. The two hormonal families were extracted separately from the same hemolymph sample and quantified by two radioimmunoassays. Juvenile hormone RIA activity was about 35 nM in larvae of the antepenultimate and penultimate stages. It dropped before each molt and increased thereafter. Moreover, it gradually decreased during the last larval instar. In pupae, it was generally low, but it rose drastically during the late pupal development and in young adults. This rise was very much higher in females than in males. Three different RIA-active compounds were found; they were assumed to be JH-I, JH-II, and JH-III according to their retention times in HPLC. The three compounds were present in almost equal concentration in larvae of the penultimate stage: JH-I predominated, however, during the last larval instar. In late pupae, the main hormone was JH-III both in males and in females. There is no clear relationship between ecdysteroid and juvenile hormone changes, except for a female-specific ecdysteroid rise which coincides with the juvenile hormone release in late pupae. This double hormonal stimulation can be involved in the regulation of vitellogenin synthesis and deposition in oocytes.     

Effects of morphine on the experimental illusion of pain produced by a thermal grill

We compared the effects of systemic morphine on normal (heat and cold) pain and paradoxical burning pain evoked by the simultaneous application of innocuous warm and cold stimuli to the skin. Twelve healthy volunteers participated in a randomised, double-blind, cross-over study to compare the effects of intravenous administration of morphine (0.025 or 0.1mg/kg) or placebo (saline). Stimuli were applied to the palm of the right hand with a thermode ("thermal grill") composed of six bars, whose temperatures were controlled by Peltier elements. For each session, we measured the heat and cold pain thresholds and then successively measured the intensity of: (i) paradoxical pain evoked by a combination of non-noxious warm and cold stimuli; (ii) "normal" pain evoked by suprathreshold heat or cold stimuli; (iii) non-painful sensations evoked by warm or cold stimuli at temperatures used to produce paradoxical pain. Measurements were performed before 20min after the administration of morphine or placebo and 5min after the administration of the morphine antagonist, naloxone. The administration of 0.1mg/kg of morphine, but not 0.025mg/kg, induced a significant and naloxone-reversible reduction of paradoxical pain intensity, which was directly correlated with the reduction of normal cold pain. No differences were observed for non-painful thermal sensations. The paradoxical burning pain evoked by a thermal grill can be modified pharmacologically by analgesics and share some mechanisms with normal pain. This unique experimental "illusion of pain" may represent a new model to test analgesics in healthy volunteers.     

Screening of human serum proteins for uranium binding

About 20% of uranyl ions in serum are associated with the protein pool. A few of them such as transferrin have been characterized, but most still have to be identified to obtain a better explanation of the biochemical toxicology and kinetics of uranium. We designed an in vitro sensitive procedure involving a combination of bidimensional chromatography with time-resolved fluorescence, coupled with proteomic analysis, to identify uranium-binding proteins in human serum fractions. Ten novel targets were identified and validated using purified proteins and inductively coupled plasma mass spectrometry. Of these, ceruloplasmin, hemopexin, and two complement proteins displayed the capacity to bind uranium with stoichiometry greater than 1 mole of uranium per mole of protein. Not all of these targets are metalloproteins, suggesting that uranyl ions can use a wide variety of binding sites and coordination strategies. These data provide additional insights into a better understanding of uranium chemical toxicity.     

Comparison of atracurium and alcuronium in day-case gynaecological surgery

Alcuronium and atracurium were used on a randomised basis as part of the anaesthetic technique for out-patient gynaecological laparoscopy. Conditions for intubation and relaxation were similar but there was a marked decrease in the incidence of minor postoperative sequelae in the atracurium group.     

Targeting the p27 E3 ligase SCF(Skp2) results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy

Decreased p27(Kip1) levels are a poor prognostic factor in many malignancies, and can occur through up-regulation of SCF(Skp2) E3 ligase function, resulting in enhanced p27 ubiquitination and proteasome-mediated degradation. While proteasome inhibitors stabilize p27(Kip1), agents inhibiting SCF(Skp2) may represent more directly targeted drugs with the promise of enhanced efficacy and reduced toxicity. Using high-throughput screening, we identified Compound A (CpdA), which interfered with SCF(Skp2) ligase function in vitro, and induced specific accumulation of p21 and other SCF(Skp2) substrates in cells without activating a heat-shock protein response. CpdA prevented incorporation of Skp2 into the SCF(Skp2) ligase, and induced G(1)/S cell-cycle arrest as well as SCF(Skp2)- and p27-dependent cell killing. This programmed cell death was caspase-independent, and instead occurred through activation of autophagy. In models of multiple myeloma, CpdA overcame resistance to dexamethasone, doxorubicin, and melphalan, as well as to bortezomib, and also acted synergistically with this proteasome inhibitor. Importantly, CpdA was active against patient-derived plasma cells and both myeloid and lymphoblastoid leukemia blasts, and showed preferential activity against neoplastic cells while relatively sparing other marrow components. These findings provide a rational framework for further development of SCF(Skp2) inhibitors as a novel class of antitumor agents.     

Laparoscopic total hysterectomy after radiochemotherapy in an obese woman with neuroendocrine carcinoma of the cervix: surgical and anesthesiological aspects

Massive obesity is an important risk factor in gynaecologic surgery. The traumatic effect of traditional laparotomy on the parietal wall is responsible for important perioperative morbidity. We describe the first reported case of an obese woman (Body Mass Index = 55 kg/m2) with stage IIA neuroendocrine carcinoma of the cervix treated by laparoscopy after radiochemotherapy. After a complete response to radiochemotherapy, the patient underwent laparoscopic hysterectomy and bilateral salpingo-oophorectomy. The laparoscopic procedure was performed with a low-pressure pneumoperitoneum. She was discharged at day 2. No major complication was observed. Surgical and anesthesiological laparoscopic management in obese women are discussed.     

High-affinity uranyl-specific antibodies suitable for cellular imaging

Monoclonal antibodies (mAbs) have proved to be valuable models for the study of protein-metal interactions, and previous reports have described very specific antibodies to chelated metal ions, including uranyl. We raised specific mAbs against UO2(2+)-DCP-BSA (DCP, 1,10-phenanthroline-2,9-dicarboxylic acid) to generate new sets of antibodies that might cross-react with various complexed forms of uranyl in different environments for further application in the field of toxicology. Using counter-screening with UO2(2+)-DCP-casein, we selected two highly specific mAbs against uranyl-DCP ( K D 10-100 pM): U04S and U08S. Competitive assays in the presence of different metal ions (UO2(2+), Fe (3+), Zn2+, Cu2+, and Ca2+) showed that uranyl in solution can act as a good competitor, suggesting some antibody ability to cross-react with chelating groups other than DCP in the UO2(2+) equatorial coordination plane. Interestingly, one of the antibodies could be used for revealing uranyl cations in cell samples. Fluorescence activated cell sorting analyses after immunolabeling revealed the interaction of uranyl with human kidney cells HK2. The intracellular accumulation of uranyl could be directly visualized by metal-immunostaining using fluorescent-labeled mAb. Our results suggest that U04S mAb epitopes mostly include the uranyl fraction and its paratopes can accommodate a wide variety of chelating groups.