Recurrent respiratory papillomatosis: an overview of current thinking and treatment

Human papillomaviruses (HPV) infection in benign laryngeal papillomas is well established. The vast majority of recurrent respiratory papillomatosis lesions are due to HPV types 6 and 11. Human papillomaviruses are small non-enveloped viruses (>8 kb), that replicate within the nuclei of infected host cells. Infected host basal cell keratinocytes and papillomas arise from the disordered proliferation of these differentiating keratinocytes. Surgical debulking of papillomas is currently the treatment of choice; newer surgical approaches utilizing microdebriders are replacing laser ablation. Surgery aims to secure an adequate airway and improve and maintain an acceptable quality of voice. Adjuvant treatments currently used include cidofovir, indole-3-carbinol, ribavirin, mumps vaccine, and photodynamic therapy. The recent licensing of prophylactic HPV vaccines is a most interesting development. The low incidence of RRP does pose significant problems in recruitment of sufficient numbers to show statistical significance. Large multi-centre collaborative clinical trials are therefore required. Even so, sufficient clinical follow-up data would take several years

A Mutation in MRH2 Kinesin Enhances the Root Hair Tip Growth Defect Caused by Constitutively Activated ROP2 Small GTPase in Arabidopsis

Root hair tip growth provides a unique model system for the study of plant cell polarity. Transgenic plants expressing constitutively active (CA) forms of ROP (Rho-of-plants) GTPases have been shown to cause the disruption of root hair polarity likely as a result of the alteration of actin filaments (AF) and microtubules (MT) organization. Towards understanding the mechanism by which ROP controls the cytoskeletal organization during root hair tip growth, we have screened for CA-rop2 suppressors or enhancers using CA1-1, a transgenic line that expresses CA-rop2 and shows only mild disruption of tip growth. Here, we report the characterization of a CA-rop2 enhancer (cae1-1 CA1-1) that exhibits bulbous root hairs. The cae1-1 mutation on its own caused a waving and branching root hair phenotype. CAE1 encodes the root hair growth-related, ARM domain-containing kinesin-like protein MRH2 (and thus cae1-1 was renamed to mrh2-3). Cortical MT displayed fragmentation and random orientation in mrh2 root hairs. Consistently, the MT-stabilizing drug taxol could partially rescue the wavy root hair phenotype of mrh2-3, and the MT-depolymerizing drug Oryzalin slightly enhanced the root hair tip growth defect in CA1-1. Interestingly, the addition of the actin-depolymerizing drug Latrunculin B further enhanced the Oryzalin effect. This indicates that the cross-talk of MT and AF organization is important for the mrh2-3 CA1-1 phenotype. Although we did not observe an apparent effect of the MRH2 mutation in AF organization, we found that mrh2-3 root hair growth was more sensitive to Latrunculin B. Moreover, an ARM domain-containing MRH2 fragment could bind to the polymerized actin in vitro. Therefore, our genetic analyses, together with cell biological and pharmacological evidence, suggest that the plant-specific kinesin-related protein MRH2 is an important component that controls MT organization and is likely involved in the ROP2 GTPase-controlled coordination of AF and MT during polarized growth of root hairs

Does accreditation stimulate change? A study of the impact of the accreditation process on Canadian healthcare organizations

<p>Abstract</p> <p>Background</p> <p>One way to improve quality and safety in healthcare organizations (HCOs) is through accreditation. Accreditation is a rigorous external evaluation process that comprises self-assessment against a given set of standards, an on-site survey followed by a report with or without recommendations, and the award or refusal of accreditation status. This study evaluates how the accreditation process helps introduce organizational changes that enhance the quality and safety of care.</p> <p>Methods</p> <p>We used an embedded multiple case study design to explore organizational characteristics and identify changes linked to the accreditation process. We employed a theoretical framework to analyze various elements and for each case, we interviewed top managers, conducted focus groups with staff directly involved in the accreditation process, and analyzed self-assessment reports, accreditation reports and other case-related documents.</p> <p>Results</p> <p>The context in which accreditation took place, including the organizational context, influenced the type of change dynamics that occurred in HCOs. Furthermore, while accreditation itself was not necessarily the element that initiated change, the accreditation process was a highly effective tool for (i) accelerating integration and stimulating a spirit of cooperation in newly merged HCOs; (ii) helping to introduce continuous quality improvement programs to newly accredited or not-yet-accredited organizations; (iii) creating new leadership for quality improvement initiatives; (iv) increasing social capital by giving staff the opportunity to develop relationships; and (v) fostering links between HCOs and other stakeholders. The study also found that HCOs' motivation to introduce accreditation-related changes dwindled over time.</p> <p>Conclusions</p> <p>We conclude that the accreditation process is an effective leitmotiv for the introduction of change but is nonetheless subject to a learning cycle and a learning curve. Institutions invest greatly to conform to the first accreditation visit and reap the greatest benefits in the next three accreditation cycles (3 to 10 years after initial accreditation). After 10 years, however, institutions begin to find accreditation less challenging. To maximize the benefits of the accreditation process, HCOs and accrediting bodies must seek ways to take full advantage of each stage of the accreditation process over time.</p

Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Regulates Cell Stress Response and Apoptosis

Severe acute respiratory syndrome virus (SARS-CoV) that lacks the envelope (E) gene (rSARS-CoV-ΔE) is attenuated in vivo. To identify factors that contribute to rSARS-CoV-ΔE attenuation, gene expression in cells infected by SARS-CoV with or without E gene was compared. Twenty-five stress response genes were preferentially upregulated during infection in the absence of the E gene. In addition, genes involved in signal transduction, transcription, cell metabolism, immunoregulation, inflammation, apoptosis and cell cycle and differentiation were differentially regulated in cells infected with rSARS-CoV with or without the E gene. Administration of E protein in trans reduced the stress response in cells infected with rSARS-CoV-ΔE or with respiratory syncytial virus, or treated with drugs, such as tunicamycin and thapsigargin that elicit cell stress by different mechanisms. In addition, SARS-CoV E protein down-regulated the signaling pathway inositol-requiring enzyme 1 (IRE-1) of the unfolded protein response, but not the PKR-like ER kinase (PERK) or activating transcription factor 6 (ATF-6) pathways, and reduced cell apoptosis. Overall, the activation of the IRE-1 pathway was not able to restore cell homeostasis, and apoptosis was induced probably as a measure to protect the host by limiting virus production and dissemination. The expression of proinflammatory cytokines was reduced in rSARS-CoV-ΔE-infected cells compared to rSARS-CoV-infected cells, suggesting that the increase in stress responses and the reduction of inflammation in the absence of the E gene contributed to the attenuation of rSARS-CoV-ΔE

Comparison of anxiety between smokers and nonsmokerswith acute myocardial infarction

Background: Increased anxiety correlates with increased complications after acute myocardial infarction. Anxiety levels and use of anxiolytic agents have not been compared between smokers and nonsmokers hospitalized because of acute myocardial infarction. Objectives: To compare anxiety level, sociodemographic factors, and clinical variables between smokers and nonsmokers hospitalized with acute myocardial infarction and to examine predictors of use of ß-blockers and anxiolytic agents among smokers and nonsmokers. Methods: Secondary data analysis of a prospective multisite study on anxiety in 181 smokers and 351 nonsmokers with acute myocardial infarction. Anxiety was measured by using the State Trait Anxiety Inventory and the anxiety subscale of the Basic Symptom Inventory within 72 hours of admission. Results: Smokers reported higher anxiety levels than nonsmokers reported on both anxiety scales. Female smokers reported the highest anxiety and peak pain levels of all, yet women were the least likely to receive anxiolytic agents. Smoking status was not a predictor for anxiety level when sex, peak pain, use of ß-blockers in the hospital, and age were controlled for. However, smokers were twice as likely as nonsmokers to receive an anxiolytic agent and 60% more likely to receive a ß-blocker in the emergency department, and smokers were 80% more likely than nonsmokers to receive an anxiolytic agent during hospitalization when these variables were controlled. Conclusions: Older female smokers are at risk for complications because they are older than their male counterparts and less likely to receive ß-blockers and antianxiety medications in the emergency department. © 2006 by AACN