Summary
Background
Chronic rhinosinusitis with nasal polyps is generally characterized by local Th2 inflammation and is categorized into two subtypes in Japan: eosinophilic chronic rhinosinusitis ...(similar to chronic rhinosinusitis with nasal polyps in western countries) and non‐eosinophilic chronic rhinosinusitis (characterized by Th1‐dominant inflammation).
Objective
To investigate local IgE production and class switch recombination to IgE in these two subtypes of chronic rhinosinusitis with nasal polyps.
Methods
The identity of IgE‐positive cells was determined using double‐immunofluorescent staining for IgE and cell‐type‐specific molecular markers. To investigate the local class switch recombination to IgE and IgE synthesis in the mucosa, we performed real‐time polymerase chain reaction to examine the mRNA expression of Th2 cytokines and class‐switch‐related molecules, including IL‐4, IL‐5, IL‐13, ε germline gene transcripts, IgE mature transcript, IgG mature transcript, RAG1, RAG2 and activation‐induced cytidine deaminase in eosinophilic polyps, non‐eosinophilic polyps and controls.
Results
The concentrations of total IgE and number of IgE‐positive cells were significantly higher in the eosinophilic polyps compared with control and non‐eosinophilic polyps. IgE‐positive cells were predominantly mast cells in eosinophilic polyps and significantly correlated with the number of FcεR1‐positive cells in the subepithelial layer. IL‐5 and IL‐13 mRNA and ε germline gene transcripts expression levels were significantly higher in eosinophilic polyps compared with control and non‐eosinophilic polyps. In contrast, the number of plasma cells and the expression of IgG mature transcripts were increased in non‐eosinophilic polyps compared with eosinophilic polyps. RAG2 mRNA was significantly increased in both eosinophilic and non‐eosinophilic polyps compared with control mucosa.
Conclusion and Clinical Relevance
The current study suggests local class switching to IgE, production of IgE and IgE localization to the surface of mast cells in eosinophilic chronic rhinosinusitis in the Japanese population. The difference in the IgE‐related profiles between eosinophilic chronic rhinosinusitis and non‐eosinophilic chronic rhinosinusitis suggests heterogeneity in the pathogenesis of chronic rhinosinusitis with nasal polyps.
To describe the features of chronic sinusitis associated with the use of tumour necrosis factor (TNF) inhibitors.
A retrospective review of the medical records between 2003 and 2011 revealed that ...five patients had developed chronic sinusitis after the start of TNF inhibitor administration and required rhinological evaluation and treatment.
The incidence of refractory sinusitis associated with TNF inhibitors was approximately 2%. Of the five patients identified, four patients were medicated with etanercept and one with infliximab. The maxillary sinus was most commonly involved and cultures of the sinus discharge revealed Pseudomonas aeruginosa in three cases. Two patients showed improvement of sinusitis with antibiotic medication, despite the continuous use of TNF inhibitor, while in two other patients, sinusitis was resistant to antibiotic medication. Another patient who had developed recurrence of sinusitis after complete remission of previous chronic sinusitis by endoscopic sinus surgery showed remission only after cessation of TNF inhibitor.
Chronic sinusitis associated with TNF inhibitors is considered to be a new disease entity, and it will become more common due to the increasing use of TNF inhibitors.
Aim: To describe the features of chronic sinusitis associated with the use of tumour necrosis factor (TNF) inhibitors. Methodology: A retrospective review of the medical records between 2003 and 2011 ...revealed that five patients had developed chronic sinusitis after the start of TNF inhibitor administration and required rhinological evaluation and treatment. Results: The incidence of refractory sinusitis associated with TNF inhibitors was approximately 2%. Of the five patients identified, four patients were medicated with etanercept and one with infliximab. The maxillary sinus was most commonly involved and cultures of the sinus discharge revealed Pseudomonas aeruginosa in three cases. Two patients showed improvement of sinusitis with antibiotic medication, despite the continuous use of TNF inhibitor, while in two other patients, sinusitis was resistant to antibiotic medication. Another patient who had developed recurrence of sinusitis after complete remission of previous chronic sinusitis by endoscopic sinus surgery showed remission only after cessation of TNF inhibitor. Conclusion: Chronic sinusitis associated with TNF inhibitors is considered to be a new disease entity, and it will become more common due to the increasing use of TNF inhibitors.
Difficulties are associated with reconstruction of middle ear bony structures in surgery for destructive lesions, including cholesteatoma. Although autologous cartilage appears to be the optimal ...choice because of its resistance to infection, the harvesting of sufficient volumes may be challenging. Therefore, regenerative medicine techniques to obtain sufficient material for reconstruction are awaited. We herein present a case of middle ear surgery for cholesteatoma with a sufficient volume of stick-shaped tissue-engineered cartilage produced from a piece of autologous auricular cartilage and autologous serum, with sufficient firmness to reconstruct bony structures. During surgery, sections of tissue-engineered cartilage were placed side by side to reconstruct the posterior canal wall. The postoperative course was uneventful. This is the first-in-human report of reconstructing middle ear bony structures with tissue-engineered cartilage. The results suggest a promising future for the satisfactory reconstruction of middle ear structures with minimal morbidity at the donor site.
Abstract Activation of resting T cells is highly dependent on dendritic cells (DCs), which take up antigens and present antigenic peptides to T cells in the context of the major histocompatibility ...complex (MHC). In this study, we generated a monoclonal antibody, which we call 1C4 that recognizes integrin αM β2 (CD11b/CD18) on the surface of conventional DCs (cDCs) and is internalized after binding. Addition of 1C4 inhibited the ability of immature DCs to phagocytose apoptotic cells. 1C4 treatment also partially inhibited the generation of cDCs from bone marrow in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that not only CD11b is involved in the phagocytosis of apoptotic cells, but also that mAb such as 1C4 may be a useful tool for the delivery of specific proteins into the cytoplasm of immature DCs.
Hypertension is a major risk factor for death and cardiovascular disease (CVD) in patients undergoing chronic haemodialysis (HD), but there is uncertainty surrounding the effects of blood pressure ...(BP) lowering on this high-risk patient group.
In a multicenter, prospective, randomized, open-label, blinded-endpoint trial, 469 patients with chronic HD and elevated BP (140-199/90-99 mmHg) were assigned to receive the angiotensin receptor blockade (ARB) olmesartan (at a dose of 10-40 mg daily; n = 235) or another treatment that does not include angiotensin receptor blockers and angiotensin-converting enzyme (ACE) inhibitors (n = 234). The primary outcomes were the following: (i) composite of death, nonfatal stroke, nonfatal myocardial infarction and coronary revascularization and (ii) all-cause death.
During a mean follow-up of 3.5 years, the mean BP was 0.9/0.0 mmHg lower in the olmesartan group than in the control group (not significant). A total of 68 patients (28.9%) in the olmesartan group and 67 patients (28.6%) in the control group had subsequent primary composite endpoints hazard ratio (HR) in the olmesartan group 1.00, 95% confidence interval (CI) 0.71-1.40, P = 0.99. All-cause deaths occurred in 38 patients (16.2%) in the olmesartan group and 39 (16.7%) in the control group (HR, 0.97; 95% CI, 0.62-1.52, P = 0.91). Olmesartan did not alter the risks of serious adverse events.
BP-lowering treatment with an ARB did not significantly lower the risks of major cardiovascular events or death among patients with hypertension on chronic HD. (Cochrane Renal Group Prospective Trial Register number CRG010600030).
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