Multidisciplinary Consideration of Potential Pathophysiologic Mechanisms of Paradoxical Erythema with Topical Brimonidine Therapy

Rosacea is a chronic inflammatory disease with transient and non-transient redness as key characteristics. Brimonidine is a selective α2-adrenergic receptor (AR) agonist approved for persistent facial erythema of rosacea based on significant efficacy and good safety data. The majority of patients treated with brimonidine report a benefit; however, there have been sporadic reports of worsening erythema after the initial response. A group of dermatologists, receptor physiology, and neuroimmunology scientists met to explore potential mechanisms contributing to side effects as well as differences in efficacy. We propose the following could contribute to erythema after application: (1) local inflammation and perivascular inflammatory cells with abnormally functioning ARs may lead to vasodilatation; (2) abnormal saturation and cells expressing different AR subtypes with varying ligand affinity; (3) barrier dysfunction and increased skin concentrations of brimonidine with increased actions at endothelial and presynaptic receptors, resulting in increased vasodilation; and (4) genetic predisposition and receptor polymorphism(s) leading to different smooth muscle responses. Approximately 80% of patients treated with brimonidine experience a significant improvement without erythema worsening as an adverse event. Attention to optimizing skin barrier function, setting patient expectations, and strategies to minimize potential problems may possibly reduce further the number of patients who experience side effects. Funding: Galderma International S.A.S., Paris, France

Biomechanical techniques to evaluate tibial rotation. A systematic review

The final publication is available at Springer via http://dx.doi.org/10.1007/s00167-011-1665-z.Purpose: This article systematically reviewed the biomechanical techniques to quantify tibial rotation, for an overview of how to choose a suitable technique for specific clinical application. Methods: A systematic search was conducted and finally 110 articles were included in this study. The articles were categorized by the conditions of how the knee was examined: external load application, physical examination and dynamic task. Results: The results showed that two-thirds of the included studies measured tibial rotation under external load application, of which over 80% of the experiments employed a cadaveric model. The common techniques used included direct displacement measurement, motion sensor, optical tracking system and universal force moment sensor. Intra-operative navigation system was used to document tibial rotation when the knee was examined by clinical tests. For dynamic assessment of knee rotational stability, motion analysis with skin reflective markers was frequently used although this technique is less accurate due to the skin movement when compared with radiographic measurement. Conclusion: This study reports various biomechanical measurement techniques to quantify tibial rotation in the literatures. To choose a suitable measurement technique for a specific clinical application, it is suggested to quantify the effectiveness of a new designed surgical technique by using a cadaveric model before applying to living human subjects for intra-operative evaluation or long-time functional stability assessment. Attention should also be paid on the study's purpose, whether to employ a cadaveric model and the way of stress applied to the knee. Level of evidence: IV