Clinical Practice Updates in the Management Of Immune Thrombocytopenia.

Immune thrombocytopenia (ITP), previously called idiopathic thrombocytopenia purpura, is an autoimmune disorder characterized by a severe reduction in peripheral blood platelet count. In healthy individuals, normal platelet count ranges from 150-450 × 109/L, while in thrombocytopenia counts fall to less than 100 × 109/L.1 In adults, the incidence of ITP is approximately two to four per 100,000.2,3 Bleeding risks, specifically hemorrhage and intracranial hemorrhage, represent the most serious complications for patients with ITP. Over the past decade, the understanding of ITP has expanded greatly, which has contributed to a number of updates in the diagnosis and treatment of the disorder.3 This article aims to briefly review the pathophysiology of ITP and summarize updates in ITP management and treatment options in the adult population.

Prediction Accuracy of Winter-Tozer Equations to Estimate Free Phenytoin Concentrations in Non-Critically Ill Hospitalized Patients.

OBJECTIVE: To assess the accuracy of the standard and revised Winter-Tozer (WT) equations of predicting free phenytoin (PHT) concentrations in non-critically ill, hospitalized patients. DESIGN: Retrospective chart review. SETTING: Single-center, large urban community hospital. PATIENTS, PARTICIPANTS: Patients with free PHT levels obtained during the study period were reviewed. Thirty-nine non-critically ill, hospitalized adults met the inclusion criteria. The study population consisted of 77% African-Americans and 77% individuals 65 years of age and older. INTERVENTIONS: PHT concentrations were measured at ambient temperature. Predicted free PHT concentrations were estimated as 10% of normalized total PHT concentrations using standard or revised WT equations in two groups of patients with hypoalbuminemia and end-stage renal disease (ESRD). MAIN OUTCOME MEASURE(S): Correlation between measured versus predicted free PHT concentrations in patients with hypoalbuminemia or ESRD. RESULTS: Strong positive correlations were identified between measured and predicted free PHT concentrations for 27 patients with hypoalbuminemia (r [the Pearson correlation coefficient] = 0.96; P < 0.001) and 12 patients with ESRD (r = 0.95; P < 0.001). CONCLUSION: This study population represented a largely understudied population in this research area. Use of traditional and revised WT equations in primarily elderly, non-critically ill African-American populations can be considered to accurately predict PHT levels in populations with altered PHT albumin binding resulting from hypoalbuminemia or ESRD and settings where free PHT levels are not readily obtainable.

Engineering and expression of a human rotavirus candidate vaccine in Nicotiana benthamiana.

BACKGROUND: Human rotaviruses are the main cause of severe gastroenteritis in children and are responsible for over 500 000 deaths annually. There are two live rotavirus vaccines currently available, one based on human rotavirus serotype G1P[8], and the other a G1-G4 P[8] pentavalent vaccine. However, the recent emergence of the G9 and other novel rotavirus serotypes in Africa and Asia has prompted fears that current vaccines might not be fully effective against these new varieties. RESULTS: We report an effort to develop an affordable candidate rotavirus vaccine against the new emerging G9P[6] (RVA/Human-wt/ZAF/GR10924/1999/G9P[6]) strain. The vaccine is based on virus-like particles which are both highly immunogenic and safe. The vaccine candidate was produced in Nicotiana benthamiana by transient expression, as plants allow rapid production of antigens at lower costs, without the risk of contamination by animal pathogens. Western blot analysis of plant extracts confirmed the successful expression of two rotavirus capsid proteins, VP2 and VP6. These proteins assembled into VLPs resembling native rotavirus particles when analysed by transmission electron microscopy (TEM). Expression of the rotavirus glycoprotein VP7 and the spike protein VP4 was also tried. However, VP7 expression caused plant wilting during the course of the time trial and expression could never be detected for either protein. We therefore created three fusion proteins adding the antigenic part of VP4 (VP8*) to VP6 in an attempt to produce more appropriately immunogenic particles. Fusion protein expression in tobacco plants was detected by western blot using anti-VP6 and anti-VP4 antibodies, but no regular particles were observed by TEM, even when co-expressed with VP2. CONCLUSION: Our results suggest that the rotavirus proteins produced in N. benthamiana are candidates for a subunit vaccine specifically for the G9P[6] rotavirus strain. This could be more effective in developing countries, thereby possibly providing a higher overall efficacy for the existing vaccines. The production of rotavirus proteins in plants would probably result in lower manufacturing costs, making it more affordable for developing countries. Further investigation is required to evaluate the immunogenic potential of the VLPs and fusion proteins created in this study.