Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone

Structural and functional substrates of tetanus toxin in an animal model of temporal lobe epilepsy

The effects of tetanus toxin (TeNT) both in the spinal cord, in clinical tetanus, and in the brain, in experimental focal epilepsy, suggest disruption of inhibitory synapses. TeNT is a zinc protease with selectivity for Vesicle Associated Membrane Protein (VAMP; previously synaptobrevin), with a reported selectivity for VAMP2 in rats. We found spatially heterogeneous expression of VAMP1 and VAMP2 in the hippocampus. Inhibitory terminals in stratum pyramidale expressed significantly more VAMP1 than VAMP2, while glutamatergic terminals in stratum radiatum expressed significantly more VAMP2 than VAMP1. Intrahippocampal injection of TeNT at doses that induce epileptic foci cleaved both isoforms in tissue around the injection site. The cleavage was modest at 2 days after injection and more substantial and extensive at 8 and 16 days. Whole-cell recordings from CA1 pyramidal cells close to the injection site, made 8–16 days after injection, showed that TeNT decreases spontaneous EPSC frequency to 38 % of control and VAMP2 immunoreactive axon terminals to 37 %. In contrast, TeNT almost completely abolished both spontaneous and evoked IPSCs while decreasing VAMP1 axon terminals to 45 %. We conclude that due to the functional selectivity of the toxin to the relative sparing of excitatory synaptic transmission shifts the network to pathogenically excitable state causing epilepsy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00429-013-0697-1) contains supplementary material, which is available to authorized users

Barbarians at the British Museum: Anglo-Saxon Art, Race and Religion

A critical historiographical overview of art historical approaches to early medieval material culture, with a focus on the British Museum collections and their connections to religion

Effects of tetanus toxin on synaptic proteins in models of temporal lobe epilepsy

Injection of tetanus toxin (TeNT), systemically or directly into the brain, has long been known to cause spastic paralysis or seizures respectively: thought to be due to disruption of inhibitory neurons and cleavage of vesicle associated membrane protein 2 (VAMP2). Here we investigate mechanisms involved in TeNT-induced chronic epilepsy in the first 16 days following injections in vivo and focally onto organotypic hippocampal slice cultures. Immunohistochemical analysis identified a spatial and temporal cleavage of both VAMP1 and VAMP2 progressing from day 2 post injection through to days 8 and 16. This was concentration dependent in slice cultures. VAMP1 has been shown to co-localise predominantly with inhibitory and VAMP2 with excitatory neurons. Contradicting previous results we have shown cleavage of both VAMP1 and VAMP2, disruption of both inhibition and excitation and direct effects of the toxin in the contralateral hippocampus. This indicates that inhibitory neurons and VAMP2 are not specifically targeted by TeNT. This project benefits from the combination of electrophysiological and immunohistochemical techniques to uncover functional changes induced by TeNT. It is also the first study of focally injected TeNT onto slice cultures and offers benefits for future long term studies of the effects of the toxin and drug screening