Effective photodynamic therapy of actinic keratoses on the head and face with a novel, self-adhesive 5-aminolaevulinic acid patch

Background:  Photodynamic therapy (PDT) is increasingly used for the treatment of actinic keratosis (AK).
Objectives:  To investigate both the efficacy of different application times and the safety of a novel patch (PD P 506 A) containing aminolaevulinic acid in the PDT of mild to moderate AK.
Methods:  Applications of PD P 506 A for 0.5, 1, 2 and 4 h were compared in a multicentre, randomized, blinded-observer, parallel-group study. After patch removal, study lesions were illuminated with red light ( λ _em ≈ 630 nm; 37 J/cm²). Study lesions were not pretreated (e.g. by curettage) prior to PDT. Efficacy was evaluated 4 and 8 weeks after treatment. Safety and tolerability were determined through laboratory analyses and documentation of both local reactions and adverse events.
Results:  A total of 149 patients were initially enrolled. Of these, 140 patients (520 lesions) completed the study according to protocol. Eight weeks after treatment, 86% of the AK lesions (74% of the patients) treated with 4-h patch application showed complete clearance. The complete clearance rates of lesions (patients) for the 2-, 1- and 0.5-h treatment arms were 73% (47%), 72% (50%) and 51% (24%), respectively. Statistically, the 4-h application was identified as the 'best treatment'. Patients with clearance seemed to experience local reactions to a greater extent than patients without clearance. Local reactions to study treatments did not exceed the expected range.
Conclusions:  The results of this first clinical efficacy study suggest excellent therapeutic outcomes with a single PD P 506 A PDT with a 4-h application.     

Effects of intravitreally and intraperitoneally injected atropine on two types of experimental myopia in chicken

Atropine, a non-selective muscarinic receptor antagonist, is currently the most potent agent used to prevent myopia in animal models and children. However, the ocular target tissues are not well defined. To learn more about the effect of atropine on experimental myopia, atropine was applied both intravitreally and systemically (intraperitoneally) to chickens wearing either negative lenses or light diffusers. Furthermore, the effect of ipsilateral intravitreal atropine on myopia development in the saline-treated fellow eye was studied. Monocular intravitreal injections of atropine were performed daily for a period of 4 successive days, starting at day 8 post-hatching. Fellow eyes received saline injections. Chicks were fitted with -7D lenses, either over the atropine-injected eyes only (unilateral "lens-induced myopia (LIM)"), or over both eyes (bilateral LIM). Other groups of chicks were fitted with translucent diffusers over the atropine-injected eyes (unilateral "form deprivation myopia (FDM)"). Finally, atropine was intraperitoneally injected for 4 days in chicks that wore monocularly -7D lenses. Refractive errors (RE) were measured with infrared photoretinoscopy and axial length (AL) with A-scan ultrasonography. Atropine prevented development of myopia in both unilateral LIM and FDM in a dose-dependent fashion. Fifty percent inhibition of myopia was observed at a dose of 25 microg (unilateral LIM) or 90 microg atropine (bilateral LIM) and complete inhibition at 750 microg; in unilateral FDM, 50% inhibition occurred at 2.5 microg and almost 100% inhibition at 250 microg. Interestingly, at the highest dose of atropine (2500 microg), the treated eyes became even more hyperopic compared to the saline-injected contralateral eyes with normal visual experience. In the bilateral LIM model, atropine suppressed development of myopia in both the treated and the saline-injected control eye. However, about 8.3 times higher doses were necessary to achieve comparable contralateral suppression. Since this ratio is lower than the vitreous volume to blood volume ratio (about 1:23 in young chicks), it seems unlikely that systemic dilution of the intravitreally injected drug can fully account for the contralateral suppression. Intraperitoneal injection inhibited myopia development only at the highest dose (2500 microg) but, strikingly, this inhibition was still less when the same dose was provided through the vitreous of the fellow eye. Both eyes seem to be coupled by a yet unknown, perhaps neuronal pathway. Estimations of the scleral concentrations of atropine after intravitreal injection are compatible with the assumption that the suppression of myopia by atropine occurs by direct inhibition of scleral chondrocytes.     

Dark chocolate reduces endothelial dysfunction after successive breath-hold dives in cool water

Objective

The aim of this study is to observe the effects of dark chocolate on endothelial function after a series of successive apnea dives in non-thermoneutral water.

Methods

Twenty breath-hold divers were divided into two groups: a control group (8 males and 2 females) and a chocolate group (9 males and 1 female). The control group was asked to perform a series of dives to 20 m adding up to 20 min in the quiet diving pool of Conflans-Ste-Honorine (Paris, France), water temperature was 27 °C. The chocolate group performed the dives 1 h after ingestion of 30 g of dark chocolate. Flow-mediated dilatation (FMD), digital photoplethysmography, nitric oxide (NO), and peroxynitrite ONOO^?) levels were measured before and after each series of breath-hold dives.

Results

A significant decrease in FMD was observed in the control group after the dives (95.28 ± 2.9 % of pre-dive values, p < 0.001) while it was increased in the chocolate group (104.1 ± 2.9 % of pre-dive values, p < 0.01). A decrease in the NO level was observed in the control group (86.76 ± 15.57 %, p < 0.05) whereas no difference was shown in the chocolate group (98.44 ± 31.86 %, p > 0.05). No differences in digital photoplethysmography and peroxynitrites were observed between before and after the dives.

Conclusion

Antioxidants contained in dark chocolate scavenge free radicals produced during breath-hold diving. Ingestion of 30 g of dark chocolate 1 h before the dive can thus prevent endothelial dysfunction which can be observed after a series of breath-hold dives.     

Who and when should we screen for prostate cancer? Interviews with key opinion leaders

Prostate cancer screening using prostate-specific antigen (PSA) is highly controversial. In this Q & A, Guest Editors for BMC Medicine’s ‘Spotlight on Prostate Cancer’ article collection, Sigrid Carlsson and Andrew Vickers, invite some of the world’s key opinion leaders to discuss who, and when, to screen for prostate cancer. In response to the points of view from the invited experts, the Guest Editors summarize the experts’ views and give their own personal opinions on PSA screening.     

M-type Phospholipase A2 Receptor Autoantibodies and Renal Function in Patients with Primary Membranous Nephropathy

Background and objectives

Loss of renal function in patients with primary membranous nephropathy cannot be reliably predicted by laboratory or clinical markers at the time of diagnosis. M-type phospholipase A₂ receptor autoantibodies have been shown to be associated with changes in proteinuria. Their eventual effect on renal function, however, is unclear.

Design, setting, participants, & measurements

In this prospective, open, multicenter study, the potential role of M-type phospholipase A₂ receptor autoantibodies levels on the increase of serum creatinine in 118 consecutive patients with membranous nephropathy and positivity for serum M-type phospholipase A₂ receptor autoantibodies was analyzed. Patients were included in the study between April of 2010 and December of 2012 and observed until December of 2013. The clinical end point was defined as an increase of serum creatinine by ≥25% and serum creatinine reaching ≥1.3 mg/dl.

Results

Patients were divided into tertiles according to their M-type phospholipase A₂ receptor autoantibody levels at the time of inclusion in the study: tertile 1 levels=20–86 units/ml (low), tertile 2 levels=87–201 units/ml (medium), and tertile 3 levels ≥202 units/ml (high). The median follow-up time of all patients in the study was 27 months (interquartile range=18–33 months). The clinical end point was reached in 69% of patients with high M-type phospholipase A₂ receptor autoantibodies levels (tertile 3) but only 25% of patients with low M-type phospholipase A₂ receptor autoantibodies levels. The average time to reach the study end point was 17.7 months in patients with high M-type phospholipase A₂ receptor autoantibodies levels and 30.9 months in patients with low M-type phospholipase A₂ receptor autoantibodies levels. A multivariate Cox regression analysis showed that high M-type phospholipase A₂ receptor autoantibodies levels—in addition to men and older age—are an independent predictor for progressive loss of renal function.

Conclusions

High M-type phospholipase A₂ receptor autoantibodies levels were associated with more rapid loss of renal function in this cohort of patients with primary membranous nephropathy and therefore, could be helpful for treatment decisions.