Medium-size-vessel vasculitis

Medium-size-artery vasculitides do occur in childhood and manifest, in the main, as polyarteritis nodosa (PAN), cutaneous PAN and Kawasaki disease. Of these, PAN is the most serious, with high morbidity and not inconsequential mortality rates. New classification criteria for PAN have been validated that will have value in epidemiological studies and clinical trials. Renal involvement is common and recent therapeutic advances may result in improved treatment options. Cutaneous PAN is a milder disease characterised by periodic exacerbations and often associated with streptococcal infection. There is controversy as to whether this is a separate entity or part of the systemic PAN spectrum. Kawasaki disease is an acute self-limiting systemic vasculitis, the second commonest vasculitis in childhood and the commonest cause of childhood-acquired heart disease. Renal manifestations occur and include tubulointerstitial nephritis and renal failure. An infectious trigger and a genetic predisposition seem likely. Intravenous immunoglobulin (IV-Ig) and aspirin are effective therapeutically, but in resistant cases, either steroid or infliximab have a role. Greater understanding of the pathogenetic mechanisms involved in these three types of vasculitis and better long-term follow-up data will lead to improved therapy and prediction of prognosis

In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization

Treating pain by inhibiting ATP activation of P2X3-containing receptors heralds an exciting new approach to pain management, and Afferent's program marks the vanguard in a new class of drugs poised to explore this approach to meet the significant unmet needs in pain management. P2X3 receptor subunits are expressed predominately and selectively in so-called C- and Aδ-fiber primary afferent neurons in most tissues and organ systems, including skin, joints, and hollow organs, suggesting a high degree of specificity to the pain sensing system in the human body. P2X3 antagonists block the activation of these fibers by ATP and stand to offer an alternative approach to the management of pain and discomfort. In addition, P2X3 is expressed pre-synaptically at central terminals of C-fiber afferent neurons, where ATP further sensitizes transmission of painful signals. As a result of the selectivity of the expression of P2X3, there is a lower likelihood of adverse effects in the brain, gastrointestinal, or cardiovascular tissues, effects which remain limiting factors for many existing pain therapeutics. In the periphery, ATP (the factor that triggers P2X3 receptor activation) can be released from various cells as a result of tissue inflammation, injury or stress, as well as visceral organ distension, and stimulate these local nociceptors. The P2X3 receptor rationale has aroused a formidable level of investigation producing many reports that clarify the potential role of ATP as a pain mediator, in chronic sensitized states in particular, and has piqued the interest of pharmaceutical companies. P2X receptor-mediated afferent activation has been implicated in inflammatory, visceral, and neuropathic pain states, as well as in airways hyperreactivity, migraine, itch, and cancer pain. It is well appreciated that oftentimes new mechanisms translate poorly from models into clinical efficacy and effectiveness; however, the breadth of activity seen from P2X3 inhibition in models offers a realistic chance that this novel mechanism to inhibit afferent nerve sensitization may find its place in the sun and bring some merciful relief to the torment of persistent discomfort and pain. The development philosophy at Afferent is to conduct proof of concept patient studies and best identify target patient groups that may benefit from this new intervention

INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY

Objective: To investigate the histopathological changes and the expression of vascular endothelial growth factor (VEGF), inducible NO-synthase (iNOS), endothelial NO-synthase (eNOS), interleukin (IL)-1 beta, and IL-17 in the rabbit middle ear mucosa after direct gastric content exposure. Methods: Exploratory controlled study in which histological and immunochemical features were studied after gastric content-induced inflammation was established in rabbits. Sixteen healthy rabbits were divided into two equal groups. Gastric contents of an animal were injected into the middle ear of the same animal for 20 days. Saline was injected into the middle ear of the animals in the control group. The rabbits were humanely killed on day 27. Inflammation was assayed by light microscopy. Immunochemical staining was performed for VEGF, iNOS, eNOS, IL-1 beta, and IL-17 expression. Experimental and control animals were examined using the same protocol. Results: The expression levels of VEGF, INOS, IL-1 beta, and IL-17 differed significantly between the experimental and control groups (p = 0.018, p = 0.010, p = 0.002, and p = 0.002, respectively). The expression level of eNOS was not significantly different between the two groups (p = 0.132). Conclusion: This study demonstrates that gastroesophagial reflux induced middle ear inflammation is associated with increased expression of VEGF, IL-1 beta, IL-17, and iNOS. (C) 2011 Elsevier Ireland Ltd. All rights reserved

Interactive Image Enhancement of CR and DR Images

There is continual pressure on the radiology department to increase its productivity. Two important links to productivity in the computed/digital radiography (CR/DR) workflow chain are the postprocessing step by technologists and the primary diagnosis step by radiologists, who may apply additional image enhancements to aid them in diagnosis. With the large matrix size of CR and DR images and the computational complexity of these algorithms, it has been challenging to provide interactive image enhancement, particularly on full-resolution images. We have used a new programmable processor as the main computing engine of enhancement algorithms for CR or DR images. We have mapped these algorithms to the processor, maximally utilizing its architecture. On a 12-bit 2688 × 2688 image, we have achieved the execution time of 465 ms for adaptive unsharp masking, window/level, image rotate, and lookup table operations using a single processor, which represents at least an order of magnitude improvement compared to the response time of current systems. This kind of performance facilitates rapid computation with preset parameter values and/or enables truly interactive QA processing on radiographs by technologists. The fast response time of these algorithms would be especially useful in a real-time radiology setting, where the radiologist’s waiting time in performing image enhancements before making diagnosis can be greatly reduced. We believe that the use of these processors for fast CR/DR image computing coupled with the seamless flow of images and patient data will enable the radiology department to achieve higher productivity

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease