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Meys, R.; Gotch, F.M.; Bunker, C.B.
doi: 10.1111/j.1365-2133.2009.09365.xpmid: 19709102
SummaryHuman immunodeficiency virus (HIV)‐related cutaneous and anogenital disease in the highly active antiretroviral therapy (HAART) era presents challenging problems for dermatologists. Immune reconstitution‐associated diseases (IRADs) are common and important consequences of HAART. Dermatologists should be aware of the cutaneous manifestations of IRAD. The prevalence of clinical human papillomavirus (HPV)‐related disease is increased in HIV and does not appear to be diminished by HAART. Many patients on HAART are dogged by persistent cutaneous warts. Anogenital precancer is also common in HIV and may be burgeoning with HAART. Clinicians should be aware of the increased risk of cervical, penile and vulval/vaginal cancers in treated and untreated patients with HIV. The increase in HPV infection in HIV‐infected individuals may be, at least partly, due to increased exposure to diverse HPV types, particularly high‐risk types that might be able to persist for longer in anogenital regions. Alternatively, persistent/emergent HPV disease in HIV infection might represent persistent or modulated immunodysregulation after HAART and be viewed as a form of IRAD. The immunopathogenesis of HPV IRAD is fascinating and possibly determined by host genotype.
Alexandroff, A.B.; Graham‐Brown, R.A.C.
doi: 10.1111/j.1365-2133.2009.09395.xpmid: 19659467
SummaryThe 67th Annual Meeting of the American Academy of Dermatology took place in San Francisco on 6–10 March 2009. The flavour of this busy but well‐organized convention was a mixture of practical, hands‐on teaching sessions, led and delivered by experts, with breakthrough cutting‐edge scientific sessions. Aesthetic dermatology comprised a significant part of the meeting. It is impossible to encompass all the important presentations made at the meeting and satellite symposiums, but we highlight here a few medical pearls on dermoscopy, melanoma and oncology, inflammatory dermatoses and community‐acquired methicillin‐resistant Staphylococcus aureus. Our report is not intended as a substitute for reading the conference proceedings, educational session handouts, online updates and related references quoted in this article.
doi: 10.1111/j.1365-2133.2009.09565.xpmid: 19863502
SummaryThe ability of cells to respond to and to mitigate environmental stress is crucial for their survival. Constitutive and facultative pigmentation have evolved in order for human skin to contend with high levels of terrestrial ultraviolet radiation (UVR). When this melanin ‘shield’ is compromised, individuals are exposed to increased skin cancer risk. The purpose of this review is to discuss new insights into the genetic basis of phenotypic risk factors for skin cancer, their connection to pigmentation and tanning, the precise molecular connections linking UVR to the tanning response, and potential methods of modulating pigmentation that avoid genotoxic damage. Highly translational implications of this research include a scientific basis on which to counsel patients regarding the carcinogenicity of UVR exposure related to tanning and potential new tanning agents that may actually protect against skin cancer by circumventing the need for UVR exposure.
Mitsui, H.; Okamoto, T.; Kanzaki, M.; Inozume, T.; Shibagaki, N.; Shimada, S.
doi: 10.1111/j.1365-2133.2009.09490.xpmid: 19863514
SummaryBackground We previously have shown that nona‐arginine protein transduction domain (R9‐PTD) induced efficient protein‐antigen (Ag) transduction of dendritic cells (DCs) in vitro, resulting in the efficient induction of strong Ag‐specific immune responses mediated by CD8+ and CD4+ T cells and in superior antitumour effects in vivo in cancer‐bearing mice.Objectives The Ag‐specific immune responses caused by intradermal (i.d.) injections of R9‐PTD‐containing protein Ags without DC preparation were investigated. We also investigated the antitumour effects by intratumoral (i.t.) injections of rR9‐containing protein Ags.Methods Synthesized SIINFEKL peptide, or recombinant ovalbumin fusion proteins (rOVA, rR9‐OVA), were directly injected into abdominal skin in naïve C57BL/6 mice. OVA‐specific cytotoxic T lymphocyte (CTL) activity, serum IgG titre and cytokine profiles were investigated. Histopathological analyses were also performed. In a cancer vaccination model, EG.7 (OVA‐cDNA transfectants thymoma) cells were inoculated intradermally in C57BL/6 mice, and the antitumour effects were evaluated by i.t. injections of rR9‐OVA in a treatment setting.Results i.d. injections of rR9‐OVA into naïve C57BL/6 mice elicited OVA‐specific CTLs and produced IgG2‐dominant immunoglobulin. The i.d. injections of rR9‐OVA also induced inflammatory cell infiltrates containing neutrophils, monocytes and lymphocytes, as well as production of inflammatory cytokines such as interferon (IFN)‐γ, interleukin‐2 and IFN‐inducible protein 10, with presenting SIINFEKL epitopes on major histocompatibility complex (MHC) class I molecules at the injection area. i.t. injections of rR9‐OVA into EG.7 tumour mass significantly suppressed tumour growth, and these effects were completely abrogated by the depletion of CD8+ T cells. These antitumour effects were superior to those elicited by i.t. injections of rR9‐OVA‐treated DCs.Conclusions i.d. injections of rR9‐containing immunogenic Ag without adjuvants simultaneously induce dual immunological effects: the induction of Tc1‐ and Th1‐dominant immune responses, and the induction of inflammatory and CTL‐mediated immune responses at the injection area by expressing Ag epitopes on MHC class I molecules as targets. This simple vaccination approach with R9‐PTD‐containing fusion proteins might be useful as prophylactic immunotherapy for cancer or infectious diseases.
Belczak, C.E.Q.; De Godoy, J.M.P.; Ramos, R.N.; De Oliveira, M.A.; Belczak, S.Q.; Caffaro, R.A.
doi: 10.1111/j.1365-2133.2009.09396.xpmid: 19785617
SummaryBackground There is good evidence for the use of compression for some clinical indications but little is known about dosimetry in compression.Objective The aim of this work was to evaluate whether or not the use of compression stockings during part of the day would help in the reduction of evening oedema in patients with clinical, epidemiological, anatomical and physiopathological (CEAP) classifications C0 and C1.Methods The effects of elastic compression stockings on volumetric variations during the working day were evaluated for the legs of two men and 18 women (40 legs). The inclusion criterion was classification as C0 (10 legs) or C1 (30 legs) according to the CEAP criteria. Participants used three‐quarter‐length elastic compression stockings (20–30 mmHg) on three consecutive days for the entire day or only for the morning or they did not use the stockings at all. Volumetry using the water displacement technique was performed in the morning and in the evening. When the patients wore the stockings only during the morning, volumetry was also performed at 13:00 h.Results Significant increases in volume were observed for both legs when stockings were not used compared with the use of stockings in the morning only. After removing the stockings, both legs had significant increases in volume in the afternoon. However, use for half the day was better than not using the stockings at all.Conclusions The use of elastic compression stockings can reduce volumetric variations during working hours, with the use of stockings for the entire day being better than for just half the day.
Amichai, B.; Nitzan, B.; Mosckovitz, R.; Shemer, A.
doi: 10.1111/j.1365-2133.2009.09414.xpmid: 19785609
SummaryBackground Onychomycosis is a common disease; topical treatment is usually poorly effective, while systemic treatment is more effective but may be associated with side‐effects. Iontophoretic drug delivery may improve drug penetration through the nail and lead to better therapeutic results.Objectives To evaluate the efficacy, safety and tolerability of topical treatments with terbinafine HCl delivered with or without an iontophoretic patch in patients with onychomycosis of the toenails.Methods Patients enrolled into the study were divided randomly into two groups. Group A was treated with terbinafine and an iontophoretic patch (at a constant current density of 100 μA cm−2). Group B was treated with terbinafine without iontophoresis. Treatment was overnight wear, every day, 5 days per week, for 4 weeks. Follow‐up period was 8 weeks from the end of treatment.Results A significant clinical response was recorded in patients of group A (active group). The percentage of patients having healthy toenail growth of more than 1·5 mm at the end of treatment was 40% compared with 11% in patients treated with terbinafine without current (passive group). The percentage of patients having fungal elements (KOH) in nail specimens decreased significantly at 8 weeks following the completion of treatment: 16% in the active group vs. 53% in the passive group. Patients in the active group reported a tingling sensation that is expected when using an iontophoretic drug delivery treatment.Conclusions The delivery of terbinafine under an electrical current of 100 μA cm−2 appears to be efficacious and safe and is well tolerated for the treatment of nail onychomycosis.
Moffatt, C.J.; Doherty, D.C.; Smithdale, R.; Franks, P.J.
doi: 10.1111/j.1365-2133.2009.09397.xpmid: 19785616
SummaryBackground Identification of factors associated with healing can help in understanding the causes of delayed healing in chronic leg ulceration, and can allow for programmes to be developed to modify these factors to improve patient outcomes.Objectives To determine factors associated with healing in patients with chronic leg ulceration of all types within a defined patient population.Methods The patients were identified within the combined acute/community leg ulcer service within Wandsworth Primary Care Trust. All identified patients agreed to be interviewed and those who were able underwent clinical and noninvasive testing to determine the cause of the ulceration. Follow ups were to a maximum of 48 weeks, with time to healing given as the principal outcome measure. Analysis was by the Cox proportional hazards model for both univariate and multivariate analysis. Results were expressed as hazard ratio with 95% confidence intervals derived from the models.Results In total, 113 patients took part in this study. Univariate analysis revealed statistically significant differences for delayed healing according to the ulcer duration (P =0·002), complexity of the ulcer aetiology (P =0·035), presence of lipodermatosclerosis (P =0·02), history of deep vein thrombosis (DVT) (P =0·03) and thrombophlebitis (P =0·03). Multivariate analysis showed that ulcer duration (P =0·014), DVT (P =0·008) and a lack of Pseudomonas on wound swab (P =0·005) were independently associated with delayed healing.Conclusions The results indicate the complexity of determining risk factors for poor healing in patients with chronic leg ulceration. There appears to be little scope for interventions to improve healing from the factors identified.
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