Does spaced education improve clinical knowledge among Family Medicine residents? A cluster randomized controlled trial

Advances in Health Sciences Education - Spaced education is a learning strategy to improve knowledge acquisition and retention. To date, no robust evidence exists to support the utility of spaced...     

Rapidly Involuting Congenital Hemangioma Associated with Profound,Transient Thrombocytopenia

Abstract: Rapidly involuting congenital hemangioma (RICH) is an uncommon, often high‐flow vascular tumor that presents at birth and involutes within the first year of life. It is clinically and histologically distinct from infantile hemangioma, kaposiform hemangioendothelioma, and tufted angioma, the latter two being associated with Kasabach–Merritt phenomenon. We present a female infant with RICH and profound, transient thrombocytopenia and review the extent and clinical course of thrombocytopenia in the context of congenital vascular tumors.     

Abnormal glucose homeostasis due to chronic hyperresistinemia

Resistin is an adipocyte-secreted protein that circulates at increased levels in obesity. Acute administration of resistin impairs glucose tolerance, but the effects of chronic hyperresistinemia have not been established. Here we describe the generation and characterization of transgenic mice that have high circulating levels of resistin in the setting of normal weight. Fasted blood glucose was higher in resistin-transgenic mice than in their nontransgenic littermates, and glucose tolerance was impaired in the hyperresistinemic mice. Metabolic studies in the setting of a hyperinsulinemic-euglycemic clamp protocol revealed that chronically hyperresistinemic mice have elevated glucose production. This increase in glucose production may be partly explained by increased expression of hepatic phosphoenolpyruvate carboxykinase. Thus, chronic hyperresistinemia impairs normal glucose metabolism.     

Role of TC21/R-Ras2 in enhanced migration of neurofibromin-deficient Schwann cells

The neurofibromatosis type 1 tumor suppressor protein neurofibromin, is a GTPase activating protein for H-, N-, K-, R-Ras and TC21/R-Ras2 proteins. We demonstrate that Schwann cells derived from Nf1-null mice have enhanced chemokinetic and chemotactic migration in comparison to wild-type controls. Surprisingly, this migratory phenotype is not inhibited by a farnesyltransferase inhibitor or dominant-negative (dn) (N17)H-Ras (which inhibits H-, N-, and K-Ras activation). We postulated that increased activity of R-Ras and/or TC21/R-Ras2, due to loss of Nf1, contributes to increased migration. Mouse Schwann cells (MSCs) express R-Ras and TC21/R-Ras2 and their specific guanine exchange factors, C3G and AND-34. Infection of Nf1-null MSCs with a dn(43N)R-Ras adenovirus (to inhibit both R-Ras and TC21/R-Ras2 activation) decreases migration by approximately 50%. Conversely, expression of activated (72L)TC21/R-Ras2, but not activated (38V)R-Ras, increases migration, suggesting a role of TC21/R-Ras2 activation in the migration of neurofibromin-deficient Schwann cells. TC21/R-Ras2 preferentially couples to the phosphatidylinositol 3-kinase (PI3-kinase) and MAP kinase pathways. Treatment with a PI3-kinase or MAP kinase inhibitor reduces Nf1-null Schwann cell migration, implicating these TC21 effectors in Schwann cell migration. These data reveal a key role for neurofibromin regulation of TC21/R-Ras2 in Schwann cells, a cell type critical to NF1 tumor pathogenesis.     

Large-scale molecular comparison of human schwann cells to malignant peripheral nerve sheath tumor cell lines and tissues

Malignant peripheral nerve sheath tumors (MPNST) are highly invasive soft tissue sarcomas that arise within the peripheral nerve and frequently metastasize. To identify molecular events contributing to malignant transformation in peripheral nerve, we compared eight cell lines derived from MPNSTs and seven normal human Schwann cell samples. We found that MPNST lines are heterogeneous in their in vitro growth rates and exhibit diverse alterations in expression of pRb, p53, p14(Arf), and p16(INK4a) proteins. All MPNST cell lines express the epidermal growth factor receptor and lack S100beta protein. Global gene expression profiling using Affymetrix oligonucleotide microarrays identified a 159-gene molecular signature distinguishing MPNST cell lines from normal Schwann cells, which was validated in Affymetrix microarray data generated from 45 primary MPNSTs. Expression of Schwann cell differentiation markers (SOX10, CNP, PMP22, and NGFR) was down-regulated in MPNSTs whereas neural crest stem cell markers, SOX9 and TWIST1, were overexpressed in MPNSTs. Previous studies have implicated TWIST1 in apoptosis inhibition, resistance to chemotherapy, and metastasis. Reducing TWIST1 expression in MPNST cells using small interfering RNA did not affect apoptosis or chemoresistance but inhibited cell chemotaxis. Our results highlight the use of gene expression profiling in identifying genes and molecular pathways that are potential biomarkers and/or therapeutic targets for treatment of MPNST and support the use of the MPNST cell lines as a primary analytic tool.     

Laugier-Hunziker syndrome: A case report and review of the literature

Laugier-Hunziker syndrome (LHS) is a rare acquired disorder characterized by diffuse macular hyperpigmentation of the oral mucosa and, at times, longitudinal melanonychia. Although LHS is considered a benign disease with no systemic manifestations or malignant potential, it is important to rule out other mucocutaneous pigmentary disorders that do require medical management. Prompt clinical recognition also averts the need for excessive and invasive procedures and treatments. To date, only four cases have been reported in the United States. We present a 77-year-old man who had clinical features typical of LHS and we then provide a review of the literature on LHS and its mimickers.     

An Algorithm for Tracking Microcatheters in Fluoroscopy

Currently, a large number of endovascular interventions are performed for treatment of intracranial aneurysms. For these treatments, correct positioning of microcatheter tips, microguide wire tips, or coils is essential. Techniques to detect such devices may facilitate endovascular interventions. In this paper, we describe an algorithm for tracking of microcatheter tips during fluoroscopically guided neuroendovascular interventions. A sequence of fluoroscopic images (1,024 × 1,024 × 12 bits) was acquired using a C-arm angiography system as a microcatheter was passed through a carotid phantom which was on top of a head phantom. The carotid phantom was a silicone cylinder containing a simulated vessel with the shape and curvatures of the internal carotid artery. The head phantom consisted of a human skull and tissue-equivalent material. To detect the microcatheter in a given fluoroscopic frame, a background image consisting of an average of the four previous frames is subtracted from the current frame, the resulting image is filtered using a matched filter, and the position of maximum intensity in the filtered image is taken as the catheter tip position in the current frame. The distance between the tracked position and the correct position (error distance) was measured in each of the fluoroscopic images. The mean and standard deviation of the error distance values were 0.277 mm (1.59 pixels) and 0.26 mm (1.5 pixels), respectively. The error distance was less than 3 pixels in the 93.0% frames. Although the algorithm intermittently failed to correctly detect the catheter, the algorithm recovered the catheter in subsequent frames.     

Amelanotic subungual melanoma after trauma: An unusual clinical presentation

Amelanotic subungual melanoma (SUM) is difficult to clinically diagnose owing to its rarity and variable presentation. We describe a case of a 63-year-old gentleman with an amelanotic SUM that developed after local trauma and presented as a persistent non-healing ulcer which was initially mistaken for a chronic infection. Because amelanotic SUM can mimic other lesions, the physician should have a high index of suspicion for SUM when managing atypical nail lesions to ensure prompt recognition and treatment. The prior trauma to the nail also suggests that posttraumatic inflammation may play a role in SUM development.