Subcutaneous immunoglobulins for the treatment of a patient with antisynthetase syndrome and secondary chronic immunodeficiency after anti-CD20 treatment: a case report

Antisynthetase syndrome is a rare and debilitating multiorgan disease characterized by inflammatory myopathy, interstitial lung disease, cutaneous involvement, and frequent chronic inflammation of the joints. ...

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Anesthetic Management of a Patient with Cowden Syndrome and Review of Anesthetic Concerns

Cowden syndrome (CS) is a rare autosomal dominant disorder demonstrating variable penetrance and an incidence of 1:200 000. The syndrome is characterized by gastrointestinal polyposis, mucocutaneous hamartomas of face and oral papillomatosis. Eighty percent of patients with CS have mutation in phosphatase and tensin homolog tumor-suppressor gene making them prone for developing malignancies of breast, thyroid and genitourinary system. Arteriovenous malformations (AVM) in brain, vertebral column and skin are also common features [1].

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Physical activity, restrictions in activity, and body mass index among urban children with persistent asthma

Asthma and obesity are public health problems that disproportionately affect underserved children. Urban children with asthma may be limited in their participation in physical activity, further increasing their risk for overweight.

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Diffuse heterotopic calcification of fibula flap: a previously unreported case

We describe what is, to the best of our knowledge, a new phenomenon, in which small multiple foci of heterotopic calcification developed in a fibular free flap that had been used to reconstruct a maxillary defect.

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Assessment of in vivo mast cell reactivity in patients with systemic mastocytosis

Abstract

Background

Patients with systemic mastocytosis (SM) have clinical signs of mast cell (MC) activation and increased levels of MC mediators. It is unclear whether the increased mediator levels are caused by increased numbers of tissue MCs, or whether these cells in affected individuals have a hyperactive phenotype.

Objective

To determine reactivity of the skin and the airways to directly acting mediators and indirectly acting mast cell secretagogues in subjects with SM.

Methods

Skin reactivity to morphine and histamine, and airway responsiveness to mannitol and methacholine was assessed in 15 patients with SM, 11 patients with allergic asthma (A) and 13 healthy controls (HC). Serum tryptase and urinary metabolites of the MC mediators histamine and prostaglandin D₂ were measured, as well as ex vivo basophil histamine release.

Results

Mast cell mediators in the blood and urine were significantly higher in patients with SM than in HC and A controls. Responsiveness to local activation of skin MCs (by morphine) and airway MCs (by mannitol) was similar in SM and HC groups. Likewise, end-organ responsiveness in the skin to histamine, and in the airways to methacholine, was similar in all three subject groups. There was no evidence of increased basophil reactivity in SM patients.

Conclusions & Clinical Relevance

Mast cells in the skin and airways of subjects with SM do not exhibit hyper-reactivity towards the MC-activating stimuli morphine and mannitol, respectively. Therefore, the highly elevated baseline levels of MC mediators in SM are most likely due to increased MC numbers, rather than altered MC responsiveness. The underlying mechanisms could involve leakage of MC mediators, or dysfunctions in mediator synthesis, storage and release. One clinical implication of our study is that there is no contraindication to perform skin tests using morphine in subjects with mastocytosis

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Interferon-γ induced insufficient autophagy contributes to p62-dependent apoptosis of epithelial cells in chronic rhinosinusitis with nasal polyps

Abstract

Background

Autophagy is a lysosomal degradation pathway that is essential for cell survival, differentiation, and homeostasis. This study aimed to investigate the contribution of autophagy to the pathogenesis of CRS with nasal polyps (CRSwNP).

Methods

The expression of autophagic proteins [microtubule-associated protein 1 light chain 3B (LC3B)-II, autophagy-related proteins (Atg), and Beclin 1], substrate proteins (p62 and ubiquitinated proteins), and apoptotic signaling molecules [cysteine-aspartic protease-3 and 8, and poly-ADP-ribose polymerase] in the sinonasal mucosa and nasal epithelial cells (NECs) was detected by immunohistochemistry and Western blotting. Autophagic vacuoles were observed with transmission electron microscopy. BEAS-2B cells and NECs were treated with rapamycin, bafilomycin A1, or various cytokines. In some experiments, cultured NECs were transfected with small interfering RNA targeting p62 (sip62) or Atg5 (siAtg5). Cultured cells were analyzed with Western blotting and flow cytometry.

Results

Although autophagic protein expression and autophagic vacuole formation were increased in both eosinophilic and non-eosinophilic CRSwNP, particularly in NECs, there was also an up-regulation of substrate proteins and apoptotic signaling molecules. IFN-γ, but not IL-4, IL-13, or IL-17A, simultaneously enhanced LC3B-II and p62 levels as well as cell apoptosis in BEAS-2B cells and/or normal NECs. Bafilomycin A1 up-regulated the levels of LC3B-II and p62 in polyp NECs and IFN-γ treated normal NECs. IFN-γ-induced apoptosis of normal NECs was exaggerated by bafilomycin A1 and siAtg5. Sip62 suppressed apoptosis of polyp NECs and IFN-γ treated NECs. IFN-γ protein levels were increased in both eosinophilic and non-eosinophilic CRSwNP.

Conclusions

IFN-γ induces activated but insufficient autophagy and thus contributes to a degree to p62-dependent apoptosis of NECs in CRSwNP.

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Serum cotinine levels should optimally be measured when evaluating the outcomes of cartilage tympanoplasty in smokers

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