Optimizing the use of topical brimonidine in rosacea management: panel recommendations.

Rosacea is a chronic inflammatory disease with a complex pathophysiology that manifests with central facial redness with or without papulopustular lesions. Often, patients with rosacea present with a constellation of signs and symptoms; for best results, the treatment plan should take into account all symptoms manifesting in the individual patient. The first available pharmacologic treatment to address the redness associated with rosacea is topical brimonidine. In the United States, brimonidine topical gel 0.33% is indicated for persistent facial erythema of rosacea; approval was based on clinically significant efficacy and good safety data from large-scale clinical trials. Use of brimonidine in routine clinical practice has yielded new insights that elaborate on the findings from clinical trials. For example, real-world use has shown that a percentage of patients (in our experience, approximately 10 to 20%) treated with brimonidine experience a worsening of erythema that has been called "rebound." Our routine use of this agent for >1 year has yielded strategies to set patient expectations, optimize treatment initiation, and minimize potential problems; this article details those strategies. Because we believe that the term "rebound" has been used to describe several physiologically distinct events, we have also proposed more specific terminology for such events.

Extracutaneous melanoma epidemiology in British Columbia.

The epidemiology of extracutaneous melanoma (ECM) is sparsely reported upon in the literature, and studies to date have been limited both by time and by geographic gaps in available data. Utilizing a comprehensive provincial cancer registry, we sought to analyze the incidence and survival rates of ECM on the basis of sex and anatomic distribution for the British Columbia, Canada population. Data on ECMs diagnosed between 1 January 1992 and 31 December 2006 were obtained from the BC Cancer Registry. Anatomical sites of ECM were classified on the basis of ICD-9 codes, and incidence rates for each site were age standardized and grouped by sex. The 5-year survival rate for each anatomical grouping was tracked until 31 December 2011. A total of 922 primary ECMs were recorded in the BC Cancer Registry between 1992 and 2006, representing 5.1% of melanoma incidence. Ocular melanomas were most frequently reported, with an age-standardized incidence rate (per million) of 10.6 for men and 8.5 for women. ECM patients were generally older at diagnosis and had poorer survival rates compared with cutaneous melanoma cases. Five-year survival rates for ECM varied markedly from 23.5% for genital lesions to 87.0% for ocular cases. Our ECM epidemiology results are largely consistent with previous studies from the USA and Europe. Where considerable differences in reported values do exist, the opportunity arises to assess the efficacy of melanoma detection, monitoring, and treatment strategies in different geographic regions. Our study represents the largest epidemiological investigation of ECM in Canada and provides a framework for future epidemiological comparisons.

Vaccinia virus activation of CCR5 invokes tyrosine phosphorylation signaling events that support virus replication.

Vaccinia virus, a poxvirus, produces structurally distinct forms of virions for which the immediate events following cell entry are ill-defined. We provide evidence that intracellular mature virus (IMV) enters both permissive and nonpermissive T-cell lines and that introduction of CCR5 into nonpermissive mouse fibroblasts or human primary T cells renders the cells permissive for vaccinia replication. Notably, T cells expressing CCR5 in which tyrosine 339 in the intracellular region is replaced by phenylalanine no longer support virus replication or virus-inducible activation of specific host cell signaling effectors IRS-2, Grb2, and Erk1/2. We show that following IMV entry into the cell, the intact but not the tyrosine-deficient CCR5 is rapidly internalized and colocalizes with virus. This colocalization precedes virus-inducible signaling and replication.

Dynamic changes in clinical features and cytokine/chemokine responses in SARS patients treated with interferon alfacon-1 plus corticosteroids.

Severe acute respiratory syndrome (SARS), caused by a novel coronavirus, emerged in early 2003 as a major international health crisis. We report on serum cytokine levels, viral load and clinical parameters over the course of the disease in a cohort of nine adult SARS patients treated with steroids and interferon alfacon-1 at North York General Hospital in Toronto, Ontario. Considerable variation among SARS patients with respect to circulating viral load and patterns of SARS-CoV-evoked cytokine responses was recorded. No single cytokine profile was observed in all patients, yet serum concentrations of interferon (IFN)-gamma, interleukin (IL)-10, CXCL10, CCL5 and CXCL8 were found to be elevated above normal levels during the course of the disease in all patients. Expression levels for IL-10, IFN-gamma and CXCL10 consistently peaked within 4 days of peak viral load. IL-12p70, IL-4 and tumour necrosis factor-alpha concentrations were consistently highest within 5 days of peak viral load. These results suggest that elevated levels of inflammatory cytokines are sensitive correlates of disease severity, including lung abnormalities and viral load in serum, and may provide a tool for monitoring disease progression in affected individuals.