Faculty Bibliography

Asthma is the most common chronic disease of childhood, with asthma exacerbations and wheezing resulting in more than 2 million emergency department visits per year. Symptoms can vary from mild shortness of breath to fatal status asthmaticus. Given the high prevalence of asthma and its potential to progress from mild to moderate to life-threatening, it is vital for emergency clinicians to have a thorough understanding of acute asthma management. Current evidence clearly supports the use of inhaled bronchodilators and systemic steroids as first-line agents. However, in those who fail to respond to nitial therapies, a variety of adjunct therapies and interventions are available with varying degrees of evidence to support their use. This review focuses specifically on evaluation and treatment of pediatric asthma in the emergency department and reviews the current evidence for various modes of treatment.

Imatinib mesylate is widely used for the treatment of patients with chronic myelogenous leukemia (CML). This compound is very efficient in killing Bcr-Abl-positive cells in a caspase-dependent manner. Nevertheless, several lines of evidence indicated that caspase-mediated cell death (i.e., apoptosis) is not the only type of death induced by imatinib. The goal of our study was to evaluate the importance of the newly described caspase-independent cell death (CID) in Bcr-Abl-positive cells. We established in several CML cell lines that imatinib, in conjunction with apoptosis, also induced CID. CID was shown to be as efficient as apoptosis in preventing CML cell proliferation and survival. We next investigated the potential implication of a recently identified mechanism used by cancer cells to escape CID through overexpression of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We showed here, in several CML cell lines, that GAPDH overexpression was sufficient to induce protection from CID. Furthermore, imatinib-resistant Bcr-Abl-positive cell lines were found to spontaneously overexpress GAPDH. Finally, we showed that a GAPDH partial knockdown, using specific short hairpin RNAs, was sufficient to resensitize those resistant cells to imatinib-induced cell death. Taken together, our results indicate that CID is an important effector of imatinib-mediated cell death. We also established that GAPDH overexpression can be found in imatinib-resistant Bcr-Abl-positive cells and that its down-regulation can resensitize those resistant cells to imatinib-induced death. Therefore, drugs able to modulate GAPDH administered together with imatinib could find some therapeutic benefits in CML patients.

In this study, we investigated in the BALB/c model, the dose-dependent protective potential of previous infection with Leishmania infantum parasites, against a high-dose challenge and showed for the first time that low-dose imprinting conferred substantial spleen resistance. Mice were immunized for 1 month or 5 months by IV route with parasite inocula ranging from 10(4) to 10(7) and from 10(3) to 10(5), respectively, and challenged for 1 month with 3 x 10(7) parasites. Liver protection was directly proportional to the parasite dose used for infection and reached 90-95% whereas, only low doses (< or =10(5)) protected spleen. Maximal spleen resistance (80%) was reached in mice infected for 5 months with 10(5) parasites. In most cases, protection was accompanied in spleen, by restored in vitro responses to Leishmania antigens. Analysis of anti L. infantum isotype responses and in vitro antigen-induced cytokine production, indicated that the acquired protection was irrespective of a Th1/Th2 imbalance.

OBJECTIVE:To evaluate the effectiveness of a new regimen of pre-emptive analgesia on the development of postoperative pain after inguinal hernia repair. DESIGN/METHODS:Prospective, double-blind, randomised study. SETTING/METHODS:University Hospital, Germany. SUBJECTS/METHODS:70 consecutive patients who had primary unilateral inguinal hernia repairs. INTERVENTIONS/METHODS:A new regimen of pre-emptive analgesia with bupivacaine that was infiltrated preoperatively, intraoperatively, and postoperatively was tested. The control group were given saline infiltrations at the same times. Pain was measured up to postoperative day 30 using the visual analogue scale (VAS), the verbal rating scale (VRS), and by recording patient-controlled use of ibuprofen suppositories. RESULTS:Pain was significantly less in the pre-emptive analgesia group than in the control group during the first 10 days postoperatively as assessed by VAS and VRS (p < 0.05). Analgesic consumption was also significantly reduced in the pre-emptive analgesia group (p < 0.05). Multivariate analysis showed that bupivacaine infiltration (pre-emptive analgesia) was associated with significantly less postoperative pain (p < 0.0001). CONCLUSION/CONCLUSIONS:This regimen of pre-emptive analgesia is an effective and safe method of reducing postoperative pain and analgesic consumption after inguinal hernia repair.