High incidence of occupational exposures among healthcare workers in Erbil, Iraq.

INTRODUCTION: The current status of percutaneous injury and mucous exposures (PMEs) of hospital workers and factors associated with the injuries have not been studied in Iraq. This study aimed to evaluate the epidemiology of PMEs with blood or body fluids that leads serious risks for healthcare workers (HCWs). METHODOLOGY: An analytic, cross-sectional survey study was conducted among HCWs in Erbil city center, Iraq. The study was performed at sevenhospitals, and 177 participants were included. The dependent variable was the occurrence of PMEs in the last year, and the independent variables were age, sex, occupation of HCWs, working site, and work duration. RESULTS: A total of 177 HCW participants included 57 nurses/midwives (32.2%), 59 doctors (33.3%), 27 laboratory workers (15.3%), and 34 paramedics/multipurpose workers (19.2%) from seven hospitals. The study concluded that 67.8% of the participants reported at least one occupational PME in the last year. In all, 13.3/person/year PME incidents were reported for nurses, 9.74/person/year for paramedics/multipurpose workers, 6.71/person/year for doctors, and 3.37/person/year laboratory workers. The mean number of PME incidents was 8.91/person/year. HCWs showed 85.0% compliance with wearing mask in risky situations. The most dangerous action for occupational exposure was blood taking (39.0%). In the univariate analysis, none of the investigated variables were found to be significantly related to PME. CONCLUSIONS: Occupational injuries and exposures in Iraqi HCWs are extremely common; awareness about protection is not sufficient. Nurses were found to be the highest risk group among HCWs. Preventive actions should be taken to avoid infection.

ErbB expression, activation, and inhibition with lapatinib and tyrphostin (AG825) in human vestibular schwannomas.

BACKGROUND: Pharmacologic agents targeted against the ErbB family, or the intracellular pathways that mediate their effects, could slow clinical progression of vestibular schwannoma (VS) in patients where other modalities carry a high risk-to-benefit ratio. OBJECTIVE: Determine the identity of the predominant ErbB dimer partners in VS tumors and assess the effects of targeted inhibition of the ErbB molecules on VS growth and proliferation, as well as apoptosis. SETTING: Academic tertiary referral center. METHODS: Coimmunoprecipitation and Western blotting of VS tissue, in vitro BrdU assays of proliferation in the presence of lapatinib and tyrphostin (AG825) using primary VS cultures, and annexin V cell death assays and cell cycle assays using propidium iodide staining were performed on HEI193 cell line derived from an neurofibromatosis type 2-associated VS. RESULTS: Activated ErbB family receptor heterodimers in VS contain predominantly epidermal growth factor receptor (EGFR) and ErbB2. A robust, dose-dependent inhibition of VS growth and proliferation with the dual EGFR/ErbB2 inhibitor, lapatinib, was demonstrated. Lapatinib also inhibited EGF-induced VS proliferation. The selective ErbB2 inhibitor, AG825, inhibited growth to a lesser extent. HEI193 demonstrated apoptosis after lapatinib treatment. CONCLUSION: Dual EGFR and ErbB2 inhibition with lapatinib or combination therapy may provide therapeutic benefit in VS treatment, but further studies are necessary.

Estrogen receptor expression in sporadic vestibular schwannomas.

HYPOTHESIS: We hypothesize that vestibular schwannomas (VSs) exhibit up-regulation of estrogen receptor (ER) at the protein level compared with control great auricular nerve (GAN). BACKGROUND: It has been reported in the literature that VS occur more commonly in women and tend to be larger and more vascular in women, and growth rate can accelerate during pregnancy. The literature contains widely divergent results on ER expression in VS, however, varying from no detectable levels to detection of ER in all samples. METHODS: Sixteen sporadic VS specimens were immediately snap-frozen after microsurgical excision and analyzed for phosphorylated and total levels of ERα with Western blot analysis. ERα expression levels were normalized to actin; then, relative expression to GAN was determined. RESULTS: All VS specimens exhibited expression of both phosphorylated and total ERα. Total ERα expression in VS is equivalent to or slightly up-regulated compared with GAN. VS specimens exhibited more pronounced up-regulation of phosphorylated (i.e., activated) levels of ERα compared with GAN. CONCLUSION: We have demonstrated that ERα expression in VS is equivalent to GAN. The phosphorylated form of the receptor is up-regulated compared with GAN, however, indicating a higher level of ERα activation in sporadic VS compared with normal nerve. Further investigation into antiestrogen therapy for VS is warranted.

Merlin knockdown in human Schwann cells: clues to vestibular schwannoma tumorigenesis.

HYPOTHESIS: To investigate the early events in molecular progression toward schwannoma tumorigenesis, we developed an in vitro model of human Schwann cell tumorigenesis by merlin knockdown. BACKGROUND: Neurofibromatosis 2 (NF2)-related and sporadic vestibular schwannoma (VS) exhibit loss of functional merlin (schwannomin). After loss of merlin expression in the Schwann cell, the initial steps toward VS tumorigenesis are unknown. Merlin, a putative tumor suppressor protein, interacts with many cellular proteins, regulating their function. Among these are receptor tyrosine kinases, including the epidermal growth factor receptor family B (ErbB) family receptors epidermal growth factor receptor and ErbB2. Functional merlin interacts with and internalizes these growth factor receptors, silencing their proliferation and survival signaling. Deregulation of CD44, the cell adhesion/signaling molecule and cancer stem cell marker, has also been implicated in VS tumorigenesis. METHODS: Merlin knockdown was performed using small interfering RNA transfection into human Schwann cell primary cultures. Knockdown was confirmed by real-time quantitative PCR, immunofluorescence, and Western analysis. Expression profiles of ErbB, merlin, and the stem cell markers nestin and CD44 were examined in knockdowns. Proliferation rate was assessed with bromodeoxyuridine incorporation, and radiation sensitivity was assessed using the Annexin assay in knockdowns versus controls. RESULTS: Merlin knockdowns demonstrated increased proliferation rate, upregulation of epidermal growth factor receptor, ErbB2, and ErbB3, CD44, and nestin. Short-term merlin depletion had no effect on gamma irradiation sensitivity compared with controls. CONCLUSION: Merlin depletion results in deregulation of ErbB receptor signaling, promotes a dedifferentiated state, and increases Schwann cell proliferation, suggesting critical steps toward schwannoma tumorigenesis.

p73 expression and function in vestibular schwannoma.

OBJECTIVES: To determine the expression of the p53 family member p73 in vestibular schwannoma (VS) and to determine the potential role of this tumor suppressor in regulating the proliferation of HEI193, a human papillomavirus E6-E7 immortalized VS cell line. METHODS: Immunohistochemical staining was used to investigate the expression of p73 in 34 cases of archived VS tissue, while Western blot analysis and immunofluorescence were performed to demonstrate the expression and localization of p73 in HEI193. After transfection of a full-length p73 plasmid (TAp73alpha), flow cytometry analysis was performed to determine the effect of p73 expression on cell cycle distribution, while annexin V-FITC (fluorescein isothiocyanate) analysis and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling) assay were used to measure apoptosis. The effect of p73 expression on ionizing radiation-induced cell death was also investigated with annexin V staining, TUNEL assay, and flow cytometry analysis. RESULTS: Of the 34 vestibular schwannoma tissues examined, p73 was expressed in 14 (41%) but was not expressed in HEI193. Transfection of p73 alone resulted in increased apoptosis and necrosis, and G(1) accumulation with concomitant induction of p21. The presence of p73 also significantly increased early apoptosis (P = .046), late apoptosis (P < .001), and necrosis (P = .009) on exposure of the HEI193 cells to ionizing radiation. CONCLUSION: Forced expression of p73, perhaps by gene therapy, to induce apoptosis directly or to sensitize VS tumors to ionizing radiation may have relevant therapeutic applications.