Obstetrical anaesthesia and analgesia in chronic spinal cord-injured women

Improved acuteand rehabilitativecareand emphasis on integrating patients into society after spinal cord injury is likely to result in increasing numbers of cord-injured women presenting for obstetrical care. Anaesthetists providing care to these women should be familiar with the complications resulting from chronic cord injury and aware that many may be aggravated by the physiological changes of normal pregnancy. These complications include reduced respiratory volumes and reserve, decreased blood pressure and an increased incidence of thromboembolic phenomena, anaemia and recurrent urinary tract infections. Patients with cord lesions above the T₅ spinal level are at risk for the life-threatening complication of autonomic hyperreflexia (AH) which results from the loss of central regulation of the sympathetic nervous system below the level of the lesion. Sympathetic hyperactivity and hypertension result in response to noxious stimuli entering the cord below the level of the lesion. Labour appears to be a particularly noxious stimulus and patients with injuries above T₅ are at risk for AH during labour even if they have not had previous AH episodes. Morbidity is related to the degree of hypertension and intracranial haemorrhage has been reported during labour and attributed to AH. We report our experience in providing care to three parturients with spinal cord injuries. Two patients had high cervical lesions, one of whom experienced AH during labour and was treated with an epidural block. The second was at risk for AH having had episodes in the past and received an epidural block to provide prophylaxis for AH. In both cases epidural blockade provided effective treatment and prophylaxis for AH. The third patient had alow thoracic cord lesion, a comfortable labour but required an urgent Caesarean section performed under general anaesthesia for placental abruption and antepartum haemorrhage. The outcome of all three maternal-neonatal pairs was excellent. We recommend antepartum anaesthesia consultation for all cordinjured mothers and an epidural block as prophylaxis against AH in all parturients with cord lesions at T₅ or above.     

Spatial variations in biomarkers of Mytilus edulis mussels at four polluted regions spanning the Northern Hemisphere

Economic and social developments have taken place at the expense of the health of the environment, both locally and on a global scale. In an attempt to better understand the large-scale effects of pollution and other stressors like climate change on the health status of Mytilus edulis, mussels were collected during the first two weeks of June 2005 at three sites (one pristine and two affected by pollution) located in each of the regions of the Canadian West Coast, the St. Lawrence estuary, the Atlantic East Coast and the northwestern coast of France, covering a total distance of some 11 000 km. The mussels were analyzed for morphologic integrity (condition factor), gametogenic activity (gonado-somatic and gonad maturation index, vitellogenin(Vtg)-like proteins), energy status (temperature-dependent mitochondrial electron transport activity and gonad lipid stores), defense mechanisms (glutathione S-transferase, metallothioneins, cytochrome P4503A activity and xanthine oxidoreductase-XOR), and tissue damage (lipid peroxidation-LPO and DNA strand breaks). The results showed that data from the reference sites in each region were usually not normally distributed, with discriminant factors reaching the number of regions (i.e. four), except for the biomarkers gonadal lipids, XOR and LPO in digestive gland. The integrated responses of the biomarkers revealed that biomarkers of stress were significantly more pronounced in mussels from the Seine estuary, suggesting that the impacts of pollution are more generalized in this area. Mussels from the Seine estuary and the Atlantic East Coast (Halifax Harbor) responded more strongly for Vtg-like proteins, but was not related to gonad maturation and gonado-somatic indexes, suggesting the presence of environmental estrogens. Moreover, these mussels displayed reduced DNA repair activity and increased LPO. Factorial analyses revealed that energy status, cytochrome P4503A activity and Vtg-like proteins were the most important biomarkers. Adaptation to warmer temperatures was reflected at the energy status levels, mussels from both the polluted and warmer sites displaying increased ratios of mitochondrial activity to lipid stores. Regional observations of biomarkers of energy status, gametogenesis and pollutant-related effects were influenced by nutrition, oxygen availability (eutrophication), and thermal history.     

Loss of XIAP protein expression by RNAi and antisense approaches sensitizes cancer cells to functionally diverse chemotherapeutics

Stable expression of short-hairpin RNAs (shRNAs) directed against the X-linked inhibitor of apoptosis (XIAP) resulted in the generation of three MDA-MB-231 cell lines (XIAP shRNA cells) with reductions in XIAP mRNA and protein levels > 85% relative to MDA-MB-231 cells stably transfected with the U6 RNA polymerase III promoter alone (U6 cells). This RNA interference (RNAi) approach dramatically sensitized these cells to killing by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Importantly, loss of XIAP also sensitized the cells to killing by taxanes but had no additional effects on killing by carboplatin and doxorubicin. The increased sensitivity of the XIAP shRNA cells to killing by TRAIL and taxanes correlated with enhanced caspase cleavage and activation, including caspase-8, and robust processing of poly(ADP-ribose) polymerase and BID compared to U6 cells. Additionally, increasing XIAP levels by adenovirus-mediated expression protected both XIAP shRNA and U6 cells from TRAIL killing in a dose-dependent manner. The effects observed by stable RNAi with respect to TRAIL sensitization were also achieved following downregulation of XIAP in Panc-1 cells treated with a second-generation, mixed-backbone antisense oligonucleotide, AEG 35156/GEM640. These data indicate that reducing XIAP protein expression by either RNAi or antisense approaches increases cancer cell susceptibility to functionally diverse chemotherapeutic agents and supports the notion that downregulation of XIAP in vivo may synergize with disease-relevant chemotherapeutic regimes, including TRAIL and taxanes, to increase the effectiveness of antineoplastic agents.