Neuroprotection by neuregulin-1 following focal stroke is associated with the attenuation of ischemia-induced pro-inflammatory and stress gene expression

Neuregulins are a family of growth factors with potent neuroprotective properties. We recently demonstrated that neuregulin-1 blocked delayed neuronal death following focal ischemic stroke in the rat. Focal ischemia results in the release of pro-inflammatory cytokines that produce profound changes in gene expression and contribute to cell death associated with stroke. Inflammatory and stress mediators are involved in the pathogenesis of focal ischemic brain damage. We examined whether neuregulin-1 can influence inflammatory and stress gene expression in the rat brain following transient middle cerebral artery occlusion (MCAO). In this study, we compared gene expression profiles in animals treated with neuregulin-1beta (NRG-1) or vehicle followed by MCAO. We used the Affymetrix GeneChip system to analyze gene expression in focal ischemia of the rat brain. Several inflammatory and stress genes were significantly induced following MCAO compared to sham controls including heat shock protein-70 (HSP70), interleukin-1beta, and macrophage chemotattractant protein-1 (JE/MCP-1). Treatment with NRG-1 attenuated the expression of many of these genes by 50% or more. In vitro studies demonstrated that NRG-1 suppressed inflammatory gene expression in activated macrophages. NRG-1 also prevented neuronal death induced by oxygen-glucose deprivation in a rat neuroblastoma cell line, suggesting that NRG-1 may have both direct and indirect neuroprotective capacity. These results demonstrate that NRG-1 can regulate inflammatory and stress gene expression and may give new insight to the molecular mechanisms involved in the neuroprotective role of neuregulins in stroke.     

Drainage, fibrinolytics, or surgery: a comparison of treatment options in pediatric empyema

Background

The current treatments of pediatric empyemas include tube thoracostomy with or without the instillation of fibrinolytics, video-assisted thoracoscopic surgery (VATS), and open thoracotomy with decortication. Whereas success has been reported for all of these techniques, VATS has been suggested as the best method because of decreased length of stay.

Methods

A chart review of children who presented with parapneumonic effusions from February 2000 to June 2002 was conducted. The patients were divided into 4 groups depending on the treatment received: group I, chest tube alone (n = 18); group II, chest tube and fibrinolytics (n = 24); group III, chest tube, fibrinolytic, and surgery (n = 5); and group IV, surgery alone (n = 6). Preadmission, in-hospital, and outcome variables for the groups were recorded and compared using the Kruskall-Wallis test, with a P value less than .05 considered significant. All the patients who received fibrinolytics (group II and III) were grouped into subjects who received immediate transpleural fibrinolytics versus those who received fibrinolytics 48 hours after chest tube insertion. Length of stay (LOS), need for surgery, and hospital costs were compared between the early and late fibrinolytic groups using the Wilcoxon rank-sum test, with a P value less than .05 considered significant.

Results

Comparison of duration of symptoms, duration of preadmit antibiotics, initial white blood cell count, total lymphocyte count, and antibiotics showed no significance among the 4 groups. When comparing outcome variables, the “nonsurgery groups” (groups I and II) had shorter LOS, intensive care unit stay, and hospital charges when compared with the “surgery groups” (groups III and IV). The timing of fibrinolytic instillation (immediate versus later) did not significantly affect in the LOS, hospital charges, or the tendency to need surgery eventually in the patients who received intrapleural fibrinolytics (group II and III combined). LOS was predicted by preadmit duration of symptoms (P = .025) and overall duration of fever (P < .01). The level of pleural glucose seemed to be predictive of need for surgery (P = .015). Overall, 11 of 54 children (20.2%) eventually needed surgery.

Conclusions

Tube drainage with intrapleural instillation of fibrinolytics can be performed successfully in a large number of children with empyemas. Ultrasound characterization of the fluid and, perhaps, glucose levels may guide surgical versus nonsurgical therapy. In centers in which percutaneous drainage and tissue plasminogen activator are available, this option may be a safe and less costly alternative to surgery.     

Surgical techniques used during caesarean section operations: results of a national survey of practice in the UK

OBJECTIVE: To determine what surgical techniques are used by obstetricians in the UK for elective and emergency caesarean section operations. STUDY DESIGN: A postal questionnaire to all members and fellows of the Royal College of Obstetricians and Gynaecologists (RCOG) resident in the UK, requesting information about the use of surgical techniques and antibiotic and anticoagulant prophylaxis for elective and emergency caesarean sections. RESULTS: The response rate was 78.7%. A range of techniques was used for all procedures in caesarean section operations. Only a few techniques were used by more than 80% of obstetricians, including double layer closure of the uterus, use of prophylactic antibiotics and Pfannenstiel abdominal entry (for elective caesarean sections). There were few large differences in practice between elective and emergency caesarean sections. In emergency operations, more obstetricians use the Joel-Cohen method of abdominal entry (32.7 versus 16%) and more usually use prophylactic antibiotics and heparin (93.2 versus 85.4% and 45.8 versus 32.9%, respectively). CONCLUSIONS: There was wide variation in the surgical techniques used by obstetricians for caesarean section operations. There is an urgent need for future research to evaluate many aspects of caesarean section operations on substantive short- and long-term outcomes.     

CT-derived estimation of cochlear morphology and electrode array position in relation to word recognition in Nucleus-22 recipients

This study extended the findings of Ketten et al. [Ann. Otol. Rhinol. Laryngol. Suppl. 175:1–16 (1998)] by estimating the three-dimensional (3D) cochlear lengths, electrode array intracochlear insertion depths, and characteristic frequency ranges for 13 more Nucleus-22 implant recipients based on in vivo computed tomography (CT) scans. Array insertion depths were correlated with NU-6 word scores (obtained one year after SPEAK strategy use) by these patients and the 13 who used the SPEAK strategy from the Ketten et al. study. For these 26 patients, the range of cochlear lengths was 29.1–37.4 mm. Array insertion depth range was 11.9–25.9 mm, and array insertion depth estimated from the surgeon's report was 1.14 mm longer than CT-based estimates. Given the assumption that the human hearing range is fixed (20–20,000 Hz) regardless of cochlear length, characteristic frequencies at the most apical electrode (estimated with Greenwood's equation [Greenwood DD (1990) A cochlear frequency–position function of several species–29 years later. J Acoust. Soc. Am. 33: 1344–1356] and a patient-specific constant as) ranged from 308 to 3674 Hz. Patients' NU-6 word scores were significantly correlated with insertion depth as a percentage of total cochlear length (R = 0.452; r2 = 0.204; p = 0.020), suggesting that part of the variability in word recognition across implant recipients can be accounted for by the position of the electrode array in the cochlea. However, NU-6 scores ranged from 4% to 81% correct for patients with array insertion depths between 47% and 68% of total cochlear length. Lower scores appeared related to low spiral ganglion cell survival (e.g., lues), aberrant current paths that produced facial nerve stimulation by apical electrodes (i.e., otosclerosis), central auditory processing difficulty, below-average verbal abilities, and early Alzheimer's disease. Higher scores appeared related to patients' high-average to above-average verbal abilities. Because most patients' scores increased with SPEAK use, it is hypothesized that they accommodated to the shift in frequency of incoming sound to a higher pitch percept with the implant than would normally be perceived acoustically.     

Using simulations and standardized patients in intervention research

Caregiving is both an art and a science; both knowledge and skills are necessary to improve the quality of care that professionals provide. Researchers are often limited in their assessment of skill performance due to inadequate and unrealistic measurement options. Simulation using standardized patients offers researchers an objective method to evaluate skill performance. This article describes the use of simulations by researchers in their quest to measure changes in violence prevention skills after an intervention program given to nurse assistants working in long-term care facilities.