The comparative effects of tacrolimus and hydrocortisone in adult atopic dermatitis: an immunohistochemical study

BACKGROUND: While many studies have demonstrated the efficacy and safety of tacrolimus ointment in the treatment of atopic dermatitis (AD), only a few have investigated the effects of tacrolimus on inflammatory cells and their cytokine gene expression in patients with AD. OBJECTIVES: To characterize further the immunophenotype of infiltrating cells and the production of certain cytokines before and after treatment with topical tacrolimus and hydrocortisone butyrate. METHODS: Nine adult patients with moderate to severe AD were treated with tacrolimus ointment, while seven control patients were treated with hydrocortisone butyrate ointment. We performed lesional skin biopsies before and after treatment. These were stained immunohistochemically with a panel of monoclonal antibodies including those to CD1a, CD3, CD4, CD8, myeloperoxidase, EG1, EG2, tryptase, interferon-gamma, interleukin (IL)-4, IL-5, IL-12, IL-13, receptors for CXC chemokines (CXCR) 3 and 4, and receptor 3 for CC chemokines. RESULTS: CD3+, CD4+ and CD8+ lymphocytes, and eosinophil and neutrophil granulocytes were significantly reduced in post-treatment tacrolimus specimens, while CD1a+ cells and mast cells were not. The expression of cytokines and chemokine receptors tested, except for CXCR3, was diminished by tacrolimus treatment. Moreover, tacrolimus produced a greater reduction of lymphocytes, eosinophils and most cytokines than that induced by hydrocortisone butyrate. CONCLUSIONS: Tacrolimus not only inhibits T-lymphocyte proliferation and cytokine production, but also plays an important role in the IL-12-induced shift from a T-helper (Th) 2 to a Th1 cytokine profile that characterizes the development of chronic AD. Tacrolimus also demonstrates wider pharmacodynamic effects than hydrocortisone.     

Multi-trajectories automatic planner for StereoElectroEncephaloGraphy (SEEG)

Purpose

StereoElectroEncephaloGraphy (SEEG) is done to identify the epileptogenic zone of the brain using several multi-lead electrodes whose positions in the brain are pre-operatively defined. Intracranial hemorrhages due to disruption of blood vessels can cause major complications of this procedure ( \(<\) 1 %). In order to increase the intervention safety, we developed and tested planning tools to assist neurosurgeons in choosing the best trajectory configuration.

Methods

An automated planning method was developed that maximizes the distance of the electrode from the vessels and avoids the sulci as entry points. The angle of the guiding screws is optimized to reduce positioning error. The planner was quantitatively and qualitatively compared with manually computed trajectories on 26 electrodes planned for three patients undergoing SEEG by four neurosurgeons. Quantitative comparison was performed computing for each trajectory using (a) the Euclidean distance from the closest vessel and (b) the incidence angle.

Results

Quantitative evaluation shows that automatic planned trajectories are safer in terms of distance from the closest vessel with respect to manually planned trajectories. Qualitative evaluation performed by four neurosurgeons showed that the automatically computed trajectories would have been preferred to manually computed ones in 30 % of the cases and were judged good or acceptable in about 86 % of the cases. A significant reduction in time required for planning was observed with the automated system (approximately 1/10).

Conclusion

The automatic SEEG electrode planner satisfied the essential clinical requirements, by providing safe trajectories in an efficient timeframe.     

New Approaches to Diagnosis and Therapy

Purpose

The detection and classification of hepatic vessels in diagnostic images are essential for hepatic pre-surgery planning. Our team has developed a tool for classification, analysis, and 3D reconstruction of the hepatic and portal systems.

Methods

Our software first extracts a graphic representation of a set of connected voxels, representing both systems. It then calculates two binary volumes representing the main part of the two venous systems. Finally, it combines these results to obtain the correct vessel classification.

Results

Segmentation steps are semi-automatic and require about 40 min to complete. Schematization and classification steps are automatic and require about 17 min for results.

Conclusion

The software provides a correct and detailed reconstruction even where pathologies have caused morphological and geometrical variations in the vessels. The time required for the entire procedure is compatible with clinical requirements, providing an efficient tool for diagnosis and surgical planning.     

Circulating CD4+ CD25brightFOXP3+ regulatory T-cells are significantly reduced in bullous pemphigoid patients

Bullous pemphigoid (BP) is the most frequent autoimmune bullous skin disease, characterised by auto-antibodies against the hemidesmosome complex. Recently, regulatory T cells (Tregs) have been implicated in the development of several autoimmune diseases; few data are available in BP, failing to demonstrate a role of this subset in disease pathogenesis. The aim of this study was to investigate the expression and phenotypes of different Tregs (CD4+ CD25brightFOXP3+ and CD8+ CD28- cells) in BP to clarify whether the depletion of this subset constitutes one mechanism of tolerance loss. The CD4+ CD25brightFOXP3 and CD8+ CD28- circulating subsets were determined by flow-cytometry in 26 untreated BP patients and compared with a group of age- and sex-matched healthy controls (HC, n?=?30). Absolute and percentage values of the CD4+ CD25brightFOXP3+ cells were significantly reduced in BP compared with HC (median CD25brightFOXP3+ expression within CD4+ cells: 1.8 vs. 3.5%, p?=?0.002); conversely, BP patients were characterised by a significant expansion of the CD25brightFOXP3- "activated" T-cell subset. CCR4 and CD62L were expressed on the majority of CD4+ CD25brightFOXP3+ cells (75.2 and 82.3%, respectively). No differences in the CD8+ CD28- subset were found between BP and HC. This is the first report showing a significant reduction of circulating CD4+ CD25brightFOXP3+ Treg frequency in BP patients.