Recent Publications by CFE Educators

The choice of treatment for psoriasis in children, as in adults, is determined by disease acuity, morphology, distribution, severity, and the presence of comorbidities, such as psoriatic arthropathy. Fortunately, most patients present with mild disease that responds adequately to topical medications. A minor subset of children will present with severe, rapidly evolving disease that requires more aggressive interventions. Advanced medical treatment with systemic and phototherapy is challenging and primarily anecdotal, as these modalities are neither well-studied nor approved for use in children. Part II of this 2-part series features an overview of systemic and light therapies including their varying degrees of effectiveness, potential side-effects and applications in clinical practice.

Students have reported several challenging aspects of the transition to clerkships, such as applying clinical knowledge, learning experientially, using clinical skills, adjusting to clinical settings, and understanding roles. In an effort to address some of these challenges, a number of medical schools have added transition courses to their curricula, but little information about these courses has been published. The authors draw on findings from a study of the design and content of 30 transition courses offered in U.S. medical schools, to examine various approaches and provide a framework to guide the design of transition courses. Most courses (83%) were between one day and one week long. The authors identified three primary course themes: presentation of new information and skills, review and application of content covered in the preclerkship curriculum, and student well-being. All courses presented new information and skills, and more than half of the courses (53%) addressed all three themes. The most common curricular topics were technical/procedural skills, safety precautions, orientation to clinical settings, review of clinical skills, and stress management. Hands-on experience was the most frequently used instructional approach. Few courses had explicit goals and objectives, and evaluation of students was rare. Transition courses can address some of the needs and challenges associated with early clerkship experiences. These courses should explicitly target areas of need that are described in the literature as well as those identified within one's own institution. They should include clear objectives, learning activities tailored to the areas of need and objectives, and student and course evaluations.

This study examined the construct validity of the Groton Maze Learning Test (GMLT) in assessing processing speed, working memory, and aspects of executive function in healthy adults. Performance on GMLT outcome measures was compared to performance on tests of psychomotor speed, working memory, and learning from the CogState computerized cognitive test battery (CGS; http://www.cogstate.com/). The factor structure of the GMLT was evaluated using exploratory factor analysis. The stability of this factor structure was examined in a large sample of patients undergoing parathyroidectomy or thyroidectomy. Results of this study suggest that the GMLT measures of spatial learning efficiency and error monitoring correlate with CogState measures of attention, working memory, and learning. Exploratory factor analysis yielded a two-factor solution of error monitoring and learning efficiency, which was stable across repeated assessments.

PURPOSE

Colonic lipomas are benign, submucosal tumours that are usually asymptomatic. Typically, they are incidentally diagnosed during colonoscopy. Due to a low prevalence, the natural history of lipomas remains largely unknown. While large (>2 cm) lesions can cause symptoms and complications, their endoscopic treatment is not routinely recommended because of prior reports of a high rate of perforation.

METHODS

We used a standardized technique of polypectomy, using endoscopic looping to resect large colonic lipomas in 8 patients and followed their clinical outcomes.

RESULTS

The mean lipoma size was 3.8+/-1.2 cm (range 2.5-6 cm). No patient developed bleeding or perforation. On follow-up (mean=13.5 months, range 2-29), there was one small residual lesion.

CONCLUSION

Colonic lipomas larger than 2 cm can be safely and efficaciously removed using endoloop assisted polypectomy technique.

Translation initiation factors have complex functions in cells that are not yet understood. We show that depletion of initiation factor eIF4GI only modestly reduces overall protein synthesis in cells, but phenocopies nutrient starvation or inhibition of protein kinase mTOR, a key nutrient sensor. eIF4GI depletion impairs cell proliferation, bioenergetics, and mitochondrial activity, thereby promoting autophagy. Translation of mRNAs involved in cell growth, proliferation, and bioenergetics were selectively inhibited by reduction of eIF4GI, as was the mRNA encoding Skp2 that inhibits p27, whereas catabolic pathway factors were increased. Depletion or overexpression of other eIF4G family members did not recapitulate these results. The majority of mRNAs that were translationally impaired with eIF4GI depletion were excluded from polyribosomes due to the presence of multiple upstream open reading frames and low mRNA abundance. These results suggest that the high levels of eIF4GI observed in many breast cancers might act to specifically increase proliferation, prevent autophagy, and release tumor cells from control by nutrient sensing.

Receptor tyrosine kinase-mediated signaling is tightly regulated by a number of cytoplasmic signaling molecules. In this report, we show that Bcr-Abl transformed chronic myelogenous leukemia (CML) cell lines, K562 and Meg-01, express the receptor for nerve growth factor (NGF), TrkA, on the cell surface; however, the NGF-mediated signal is not particularly strong. Treatment with imatinib, a potent inhibitor of Bcr-Abl tyrosine kinase, downmodulates phosphorylation of downstream molecules. Upon stimulation with NGF, Erk and Akt are phosphorylated to a much greater degree in imatinib-treated cells than in untreated cells. Knockdown of expression of Bcr-Abl using small interfering RNA technique also enhanced NGF-mediated Akt phosphorylation, indicating that Bcr-Abl kinase modifies NGF signaling directly. Imatinib treatment also enhanced NGF signaling in rat adrenal pheochromocytoma cell line PC12 that expresses TrkA and c-Abl, suggesting that it is not only restoration of responsiveness to NGF after blocking oncoprotein activity, but also c-Abl tyrosine kinase per se may be a negative regulator of growth factor signaling. Furthermore, inhibition of Abl tyrosine kinase enhanced clearance of surface TrkA after NGF treatment and simultaneously enhanced NGF-mediated signaling, suggesting that as in neuronal cells 'signaling endosomes' are formed in hematopoietic cells. To examine the role of TrkA in CML cells, we studied cell growth or colony formation in the presence or absence of imatinib with or without NGF. We found that NGF treatment induces cell survival in imatinib-treated CML cell lines, as well as colony formation of primary CD34+ CML cells, strongly suggesting that NGF/TrkA signaling contributes to aberrant signaling in CML.

Despite the evidence for a significant contribution of brainstem serotonergic (5HT) systems to the control of spinal cord "pain" transmission neurons, attention has turned recently to the influence of nonserotonergic neurons, including the facilitatory and inhibitory controls that originate from so-called "on" and "off" cells of the rostroventral medulla (RVM). Unclear, however, is the extent to which these latter circuits interact with or are influenced by the serotonergic cell groups. To address this question we selectively targeted expression of a transneuronal tracer, wheat germ agglutinin (WGA), in the 5HT neurons so as to study the interplay between the 5HT and non-5HT systems. In addition to confirming the direct medullary 5HT projection to the spinal cord we also observed large numbers of non-5HT neurons, in the medullary nucleus reticularis gigantocellularis and magnocellularis, that were WGA-immunoreactive, i.e., were transneuronally labeled from 5HT neurons. FluoroGold injections into the spinal cord established that these reticular neurons are not only postsynaptic to the 5HT neurons of the medulla, but that most are also at the origin of descending, bulbospinal pathways. By contrast, we found no evidence that neurons of the midbrain periaqueductal gray that project to the RVM are postsynaptic to midbrain or medullary 5HT neurons. Finally, we found very few examples of WGA-immunoreactive noradrenergic neurons, which suggests that there is considerable independence of the monoaminergic bulbospinal pathways. Our results indicate that 5HT neurons influence "pain" processing at the spinal cord level both directly and indirectly via feedforward connections with multiple non-5HT descending control pathways.

PURPOSE

We evaluated the effectiveness of endovascular therapy for severe renal hemorrhage.

MATERIALS AND METHODS

We retrospectively reviewed cases compiled from the trauma database, billing records and interventional radiology logs at our institution from 1990 to 2007. Technical success was defined as the cessation of bleeding after angiographic embolization. Clinical success was defined as the absence of recurrent hematuria without the need for additional embolization.

RESULTS

A total of 26 patients underwent angiography and endovascular treatment for renal hemorrhage. Mean patient age was 42 years (median 37, range 7 to 70). There were 20 males and 6 females. Mean clinical followup was 11.7 months. The mechanisms of injury were iatrogenic in 6 cases (renal biopsy in 5 and post-percutaneous nephrostomy placement in 1), trauma in 16 (blunt in 10 and penetrating in 6) and spontaneous rupture of a renal mass in 4. At presentation 16 patients (62%) were hemodynamically stable, while 10 (38%) were in shock. A total of 11 patients (42%) presented with gross hematuria, 7 (27%) had microscopic hematuria and 8 (31%) had no evidence of hematuria. A total of 16 patients (62%) had kidney injuries alone, while 10 (38%) also had significant concurrent injuries. Treatment failed in all 5 grade 5 acute renal injuries (100%) caused by external trauma. Technical and clinical success was achieved in 22 (85%) and 17 patients (65%), respectively.

CONCLUSIONS

Superselective embolization therapy for renal trauma provides an effective and minimally invasive means to stop bleeding. Overall our complication rate was minimal. Most renal traumas, including most grade 4 injuries, were effectively managed by conservative therapy. Embolization proved effective for grade 4 renal trauma for which conservative therapy failed. In our series embolization failed when applied to grade 5 injuries.