Two new mutations in the HIF2A gene associated with erythrocytosis

Congenital or familial erythrocytosis/polycythemia can have many causes, and an emerging cause is genetic disruption of the oxygen‐sensing pathway that regulates the Erythropoietin (EPO) gene. More specifically, recent studies have identified erythrocytosis‐associated mutations in the HIF2A gene, which encodes for Hypoxia Inducible Factor‐2α (HIF‐2α), as well as in two genes that encode for proteins that regulate it, Prolyl Hydroxylase Domain protein 2 (PHD2) and the von Hippel Lindau tumor suppressor protein (VHL). We report here the identification of two new heterozygous HIF2A missense mutations, M535T, and F540L, both associated with erythrocytosis. Met‐535 has previously been identified as a residue mutated in other patients with erythrocytosis; although, the mutation of this particular residue to Thr has not been reported. In contrast, Phe‐540 has not been reported as a residue mutated in erythrocytosis, and we present evidence here that this mutation impairs interaction of HIF‐2α with both VHL and PHD2. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.     

Prevalence of upper aerodigestive symptoms in patients who underwent thyroidectomy with and without the use of intraoperative laryngeal nerve monitoring

Background: Upper aerodigestive symptoms (UADS) have been reported by patients who have had thyroidectomies. This study evaluated the long-term prevalence of UADS after thyroidectomy in patients who did and who did not have intraoperative neuromonitoring (IONM). Methods: This was a cross-sectional study of patients with normal vocal fold mobility who had a thyroidectomy. It included patients who did and did not have this surgery with IONM. All patients answered a questionnaire regarding UADS occurring one or more years after thyroidectomy. The questionnaire dealt with UADS relating to voice and swallowing symptoms and sought to quantify their severity. The 208 patients who underwent thyroidectomy without IONM were designated the control group (CG). The 100 patients who underwent thyroidectomy with IONM were designated the neuromonitored group (NMG). Results: The proportion of patients in the CG who reported UADS was 45%; 25.9% of these patients reported voice symptoms, and 33.6% reported swallowing symptoms. The proportion of patients in the NMG who reported UADS was 39%; 27% of these patients reported voice symptoms, and 22% reported swallowing symptoms. Thus, patients in the CG had more swallowing symptoms and a greater severity of UADS-related symptoms than patients in the NMG. Conclusions: In this study, IONM had a favorable effect in terms of decreasing the prevalence and severity of UADS occurring one year or more after thyroidectomy.     

Structural and pharmacological profile of generic enoxaparins used in Brazil

Generic active pharmaceutical ingredients (APIs) have been commonly used in Brazil, since 1999, but most of them are synthetic and small molecules. Recently, a large number of generic enoxaparins were introduced into the market raising concerns related to product-to-product interchangeability, efficiency, and drug counterfeiting. These drugs are produced from biological sources and their production involves complex procedures and purification processes. The present article evaluates several generic enoxaparins, structurally and pharmacologically, and compares them with the branded products. Structural analysis showed that the generic products are, indeed, quite similar to the branded products, however, this similarity cannot be extended to their pharmacological activities. The results showed that generic products must go through extensive structural, pharmacological, and clinical evaluation in order to assess their quality, efficacy and, ultimately, avoid drug counterfeiting before clinical use. Variation was also observed between the branded products, showing that such drugs must be at constant surveillance.     

Giant-cell glioblastoma of childhood associated with HIV-1 and JC virus coinfection

Purpose

John Cunningham (JC) viral DNA sequence has seldom been reported in patients with brain tumors such as high grade gliomas and medulloblastomas, pointing to a role in the etiopathogenesis of such tumors.

Results

We present a unique clinical case of an HIV-positive pediatric patient with multifocal leukoencephalopathy and confirmed JC virus (JCV) infection that developed a giant-cell glioblastoma.

Conclusions

Experimental data with infected primates has previously hypothesized an association of human giant-cell glioblastoma with JCV or progressive multifocal leukoencephalopathy, though such association has not been documented in the literature for humans. Future studies with larger cohorts and molecular pathological analyses are still needed to corroborate the role of the widely spread human neurotropic virus in early transformation and in the development of brain tumors with different histology in the setting of HIV-related severe immunosuppression.     

A new intraoral device to facilitate preparation of the guide plane for removable dental prostheses

This article presents a prototype of an intraoral device that facilitates preparation of parallel guide planes with accuracy and minimal occlusal divergence. The design of this device facilitates transfer of the desired path of insertion from the diagnostic cast to the mouth quickly and efficiently.     

The influence of master cast technique on the cast precision of implant-retained fixed prostheses

The aim of this study was to evaluate the precision of three different mold filling techniques in order to obtain a cast simulating a three-unit, implant-retained, fixed prosthesis. Thirty casts (n = 10) were obtained using three different mold filling techniques. Group 1 used a unique fulfillment technique, Group 2 used a two-step fulfillment technique, and Group 3 used a latex cylinder technique. Using a metallic matrix, a titanium substructure was created to simulate a three-unit fixed prosthesis used as reference to evaluate the marginal misfit and tension forces in each cast. The vertical misfit was measured by an optical microscope with an increase of 120X and by an analysis unit using the one-screw test. The tension was quantified using strain gauges. The strain results showed a statistical difference between Group 3 and the other groups. The Tukey test showed no difference between the different treatment groups (p = 0.05). All three techniques were deemed efficient; however, considering that the cylinder latex technique induced less force toward the implants, it is the preferable technique for daily clinical practice.     

Three-dimensional mapping of ozone-induced injury in the nasal airways of monkeys using magnetic resonance imaging and morphometric techniques

Age-related changes in gross and microscopic structure of the nasal cavity may alter local tissue susceptibility as well as the dose of inhaled toxicant delivered to susceptible sites. This article describes a novel method for the use of magnetic resonance imaging, 3-dimensional airway modeling, and morphometric techniques to characterize the distribution and magnitude of ozone-induced nasal injury in infant monkeys. Using this method, we generated age-specific, 3-dimensional, epithelial maps of the nasal airways of infant Rhesus macaques. The principal nasal lesions observed in this primate model of ozone-induced nasal toxicology were neutrophilic rhinitis, along with necrosis and exfoliation of the epithelium lining the anterior maxilloturbinate. These lesions, induced by acute or cyclic (episodic) exposures, were examined by light microscopy, quantified by morphometric techniques, and mapped on 3-dimensional models of the nasal airways. Here, we describe the histopathologic, imaging, and computational biology methods developed to precisely characterize, localize, quantify, and map these nasal lesions. By combining these techniques, the location and severity of the nasal epithelial injury were correlated with epithelial type, nasal airway geometry, and local biochemical and molecular changes on an individual animal basis. These correlations are critical for accurate predictive modeling of exposure-dose-response relationships in the nasal airways, and subsequent extrapolation of nasal findings in animals to humans for determining risk.