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Nguyen H.P.,Baylor College of Medicine | Ramirez-Fort M.K.,Center for Clinical Studies | Rady P.L.,University of Texas Health Science Center at Houston
Current Problems in Dermatology (Switzerland) | Year: 2014

Human papillomaviruses (HPVs) are small, double-stranded DNA viruses that cause lesions in cutaneous and mucosal tissue and are responsible for carcinomas of the cervix, vagina, vulva and penis. HPVs sort into 5 genera with a total of approximately 150 species that have been sequenced. Its genome is comprised of an early (E) region encoding the viral regulatory proteins, a late (L) region encoding the viral structural proteins and a noncoding region that is essential to the viral life cycle. For infection to occur, the virus must access the basal epidermal layer where, following endocytosis and viral capsid disassembly, the L2 protein mediates viral genome transfer to the nuclei of mitotic keratinocytes. The viral genome is maintained in episomal form during the normal life cycle and replicates in synchrony with the host cell DNA under the mediation of E1, E2, E4 and E5 viral proteins. In most high-grade cervical neoplasms, however, the viral DNA is integrated into the host genome through the disruption of the E2 open reading frame. The oncoproteins E6 and E7, which were previously suppressed by E2, are then free to inhibit the Rb and p53 tumor suppressor pathways. The viral life cycle concludes with the packaging of the viral genome and virus release, which entails the E2-mediated recruitment of L2 to regions of replication, the expression of L1 and the assembly of the icosahedral capsid in the nucleus. Overall, the complex biology of HPV continues to be an important area of research with substantial implications for public health. © 2014 S. Karger AG, Basel.

Lokhandwala J.,Jacksonville University | Best P.J.M.,Mayo Medical School | Henry Y.,00 North Academy Avenue | Berger P.B.,Center for Clinical Studies
Current Allergy and Asthma Reports | Year: 2011

Clopidogrel is a widely used antiplatelet agent, particularly after coronary stent implantation. About 1% of patients have allergic or hematologic adverse reactions to clopidogrel. This has important therapeutic implications, as premature discontinuation of clopidogrel is the strongest risk factor for stent thrombosis. Clopidogrel allergy most commonly manifests as a rash. It is important to distinguish this from other causes of rash occurring in patients who have had a recent coronary stent. Although antihistamines and short-term oral corticosteroids are effective in treating most clopidogrel hypersensitivity reactions, some persistent reactions may require discontinuation of clopidogrel. When discontinuation of clopidogrel is required, substitution with an alternative thienopyridine such as ticlopidine traditionally has been performed. However, a recent study suggests that there may be as high as a 27% risk of recurrence of non-life-threatening allergic reactions in such patients, which are usually similar to the allergic reactions that occurred with clopidogrel. No data are available regarding the frequency of cross-reactivity to prasugrel and ticagrelor; these may be potential therapeutic options in some patients. © 2010 Springer Science+Business Media, LLC.

Gordon R.,Center for Clinical Studies
Skin therapy letter | Year: 2012

Biologic compounds are being used more frequently to treat a multitude of systemic inflammatory conditions. These novel compounds are composed of antibodies or other peptides that act through one of three mechanisms: inhibiting inflammatory cytokine signaling (typically tumor necrosis factor or TNF), inhibiting T-cell activation, or depleting B-cells. The increase in use and ever expanding list of new immune modulating therapies make knowledge of the infectious complications associated with immune modulation even more important. Of particular concern is the risk for developing atypical and opportunistic infections including tuberculosis, herpes zoster, Legionella pneumophila, and Listeria monocytogenes.

Mendoza N.,Center for Clinical Studies | Mendoza N.,El Bosque University | Tyring S.K.,University of Texas Health Science Center at Houston
Expert Opinion on Emerging Drugs | Year: 2010

Importance of the filed: With the worldwide surge of MRSA, skin and skin-structure infection (SSTI) treatment has become a challenge for physicians. Cultures and antibiotic susceptibility tests for SSTIs are the rule due to the implication in morbidity and mortality rates associated with MRSA infections. The need for new antibiotics is evident and the effort to decrease antibiotic resistance is a world priority. Areas covered in this review: This manuscript accesses the actual treatments and the developing of antibiotics for MRSA SSTIs. What the reader will gain: This is a review of the data on the available and emerging treatments for MRSA SSTIs. Take home message: There is an unmet medical need for new antibiotics in the new millennium. As physicians, we must assure all appropriate procedures are completed in order to reduce the bacterial resistance, especially for MRSA. © 2010 Informa UK, Ltd.

Berger P.B.,Center for Clinical Studies | Bhatt D.L.,Harvard University | Fuster V.,Mount Sinai Medical Center | Steg P.G.,University Paris Diderot | And 8 more authors.
Circulation | Year: 2010

Background-Uncertainty exists about the frequency, correlates, and clinical significance of bleeding with dual antiplatelet therapy (DAPT), particularly over an extended period in a stable population. We sought to determine the frequency and time course of bleeding with DAPT in patients with established vascular disease or risk factors only; identify correlates of bleeding; and determine whether bleeding is associated with mortality. Methods and Results-We analyzed 15 603 patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial, a double-blind, placebo-controlled, randomized trial comparing long-term clopidogrel 75 mg/d versus placebo; all patients received aspirin (75 to 162 mg) daily. Patients had either established stable vascular disease or multiple risk factors for vascular disease without established disease. Median follow-up was 28 months. Bleeding was assessed with the use of the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) criteria. Severe bleeding occurred in 1.7% of the clopidogrel group versus 1.3% on placebo (P=0.087); moderate bleeding occurred in 2.1% versus 1.3%, respectively (P<0.001). The risk of bleeding was greatest the first year. Patients without moderate or severe bleeding during the first year were no more likely than placebo-treated patients to have bleeding thereafter. The frequency of bleeding was similar in patients with established disease and risk factors only. In multivariable analysis, the relationship between moderate bleeding and all-cause mortality was strong (hazard ratio, 2.55; 95% confidence interval, 1.71 to 3.80; P<0.0001), along with myocardial infarction (hazard ratio, 2.92; 95% confidence interval, 2.04 to 4.18; P<0.0001) and stroke (hazard ratio, 4.20; 95% confidence interval, 3.05 to 5.77; P<0.0001). ConclusionS-: In CHARISMA, there was an increased risk of bleeding with long-term clopidogrel. The incremental risk of bleeding was greatest in the first year and similar thereafter. Moderate bleeding was strongly associated with mortality. © 2010 American Heart Association, Inc.

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