Erica N. Grant

Differential effects of PPARγ agonists on the metabolic properties of gliomas and astrocytes

Recent studies show that thiazolinediones (TZDs), agonists of the peroxisome proliferator-activated receptor gamma (PPARgamma), induce apoptosis in glioma and glioblastoma cells. Here we compared the effects of troglitazone (Trog), a TZD with low affinity for binding to PPARgamma but with potent metabolic effects, on survival and metabolism in GL261 glioma cells versus primary astrocytes. Trog dose-dependently induced cell death in GL261 cells (with over 90% death at 30 microM) but did not cause any toxicity in astrocytes at the same doses. Measurements of glucose and lactate levels after incubation with Trog (30 microM) indicated an overall increase of glucose consumption and lactate production in both cell types. In astrocytes the ratio of lactate produced to glucose utilized was not significantly altered by Trog, while in glioma cells this ratio was decreased by about 40%. Trog dose-dependently reduced mitochondrial membrane potential (DeltaPsi(m)) in both cell types; and the loss of DeltaPsi(m) was greater in the tumor cells (90% loss at 20 microM) than in astrocytes (70% loss at 20 microM). These results suggest that differences in metabolic responses could contribute to the selective resistance of astrocytes to cytotoxic effects of Trog. TZDs such as Trog should therefore be considered for testing in treatment of gliomas.

Continuous Spinal Analgesia for Labor and Delivery: An Observational Study with a 23-Gauge Spinal Catheter.

BACKGROUND:The aim of the study was to assess postdural puncture headache, pain relief, motor blockade, and success rate of conversion to cesarean delivery anesthesia of a 23-gauge spinal catheter (Wiley Spinal®) for labor analgesia. METHODS:After insertion of the spinal catheter, intrathecal bupivacaine 2.5 mg was administered, followed by patient-controlled intrathecal analgesia (basal infusion of 0.0625% bupivacaine with fentanyl 2 &mgr;g/mL at a rate of 2 mL/h, demand bolus 1 mL, lockout interval 20 minutes). Bupivacaine 0.5%, up to 25 mg, was administered via the catheter along with fentanyl 20 &mgr;g for cesarean delivery anesthesia, if necessary. The catheter was removed after delivery or after 12 hours, whichever was longer. RESULTS:One hundred thirteen women were enrolled. In 12 women (11%), the catheter was not successfully inserted or maintained in position. Continuous spinal analgesia was used in 101 women. Three women (2.6%, 95% confidence interval, 0.7%–8.1%) developed postdural puncture headache. There were 83 spontaneous, 12 operative vaginal, and 18 cesarean deliveries. Of the 18 cesarean deliveries, 16 had continuous spinal analgesia when the decision was made to perform a cesarean delivery; conversion from labor analgesia to cesarean anesthesia was successful in 15 women (94%, 95% confidence interval, 67.7%–99.7%). CONCLUSIONS:The 23-gauge spinal catheter can be used for analgesia for labor. It can also be converted to surgical anesthesia for cesarean deliveries. Further studies are warranted to determine whether the spinal catheter will be a useful addition to the neuraxial techniques available for obstetric anesthesia care.

Neuraxial analgesia effects on labour progression: facts, fallacies, uncertainties and the future

Approximately 60% of women who labour in the USA receive some form of neuraxial analgesia, but concerns have been raised regarding whether it negatively impacts the labour and delivery process. In this review, we attempt to clarify what has been established as truths, falsities and uncertainties regarding the effects of this form of pain relief on labour progression, negative and/or positive. Additionally, although the term ‘epidural’ has become synonymous with neuraxial analgesia, we discuss two other techniques, combined spinal‐epidural and continuous spinal analgesia, that are gaining popularity, as well as their effects on labour progression.

A Randomized Control Trial of Bupivacaine and Fentanyl versus Fentanyl-only for Epidural Analgesia during the Second Stage of Labor

Background:The purpose of this prospective, double-blinded, parallel-arm, randomized trial was to examine the effects of epidural bupivacaine on the length of the second stage of labor in nulliparous women. Methods:The authors assessed length of second-stage labor, degree of motor blockade, mode of delivery, and visual analog scores in 310 nulliparous women with labor epidurals randomized to receive either: (1) 0.125% bupivacaine and fentanyl 2 &mgr;g/ml or (2) fentanyl 10 &mgr;g/ml alone via epidural using double blinding. Results:The median duration of the second stage was 75 min (41, 128) in the bupivacaine/fentanyl group versus 73 min (42, 120) in the fentanyl-only group (P = 0.17) with a median difference of 6.0 (95% CI, −6.0 to 18.0). Furthermore, there was no difference in degree of motor blockade, incidence of operative delivery, visual analog scores, or neonatal outcomes between the two groups. No adverse events were reported. Conclusions:Use of epidural bupivacaine/fentanyl or a fentanyl-only infusion during the second stage of labor did not affect the duration of the second stage of labor, degree of motor blockade, mode of delivery, pain relief, and maternal or neonatal outcomes. However, in the fentanyl-only infusion group, there was a fivefold increase in opioid exposure to the fetus with unknown effects on neurobehavior, an outcome not assessed beyond the immediate postnatal period in this study.

Active Warming during Cesarean Delivery: Should We SCIP It?

BACKGROUND The purpose of this open, cluster randomized controlled trial was to evaluate whether use of a fiber optic-regulated warming mattress would decrease the incidence of hypothermia in women undergoing cesarean delivery. PATIENTS AND METHODS A total of 484 women were randomized via the cluster method on a rotating weekly basis allocating participants to either use of the warming mattress or the standard method of warming at Parkland Hospital (heat-retaining caps, warmed intravenous and irrigation fluids, and warmed blankets). The primary outcome of interest was maternal hypothermia. Surgical site infections and neonatal outcomes were also assessed. RESULTS The incidence of maternal hypothermia at the conclusion of the surgery was decreased in the warming mattress group, 67 versus 80% in the standard method group (p = 0.013). There were no significant differences in maternal hypothermia at delivery or on arrival to the postanesthesia care unit. The difference in surgical site infections and neonatal outcomes were nonsignificant. CONCLUSION Use of a warming mattress reduced the incidence of maternal hypothermia at the conclusion of surgery; however, on admission to the postanesthesia care unit, these effects had dissipated.

Dual presentation of a giant left ventricular pseudoaneurysm and true aneurysm.

With medical advances, mortality and morbidity rates associated with myocardial infarction (MI) have declined dramatically (1). Nevertheless, cardiogenic shock is the most common cause of death after an acute MI, followed by left ventricular (LV) rupture (2). A pseudoaneurysm, albeit rare (3), is more likely to rupture than is a true aneurysm and thus is a post-MI complication that warrants urgent surgery (4). It is usually the result of an infarction involving the entire thickness of the myocardium. A localized pericarditis develops, and the resulting adhesions between the visceral and parietal pericardium rupture, with extravasated blood being contained by the adherent pericardium. The aneurysmal wall contains dense fibrous tissue but lacks myocardial fibers and coronary arteries. A true aneurysm, in contrast, consists of focal convex deformities of the heart, has wide communications between the aneurysmal cavity and left ventricle, contains myocardial fibers, and is lined by the former endothelium (3). This area of thin myocardium subsequently moves dyskinetically (5). Figure ​Figure11 illustrates the two differing pathologies (3).