The association between drugs and bullous pemphigoid

Abstract

Drug-induced bullous pemphigoid (DIBP) is often poorly defined in the existing literature from the classic, spontaneous form of bullous pemphigoid (BP). The pathogenesis is unclear and the association between bullous pemphigoid and various medications is tenuous^1-2.Commonly reported associations include neuroleptics^3-4and diuretics^{3, 5} with more recent literature drawing attention to dipeptidyl peptidase-4 inhibitors⁶.Strength of drug causality associations is generally determined by factors such as latency between drug initiation and onset of disease, epidemiological risk, effects of withdrawal/re-challenge. Prior drug association studies were based on broader inclusion criteria and may overestimate the true association^3-6.

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Hydroxychloroquine prescribing and monitoring practices among Irish dermatologists and rheumatologists

Abstract

Hydroxychloroquine (HCQ) is an effective drug that is widely used to treat connective tissue and autoimmune diseases. Overall, it has an excellent safety profile; however, its most potentially serious and irreversible side-effect is retinal toxicity. The Royal College of Ophthalmologists (RCO) published their recommendation on HCQ and ocular toxicity screening in 2009.

This article is protected by copyright. All rights reserved.

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Recurrence of Stevens–Johnson syndrome and toxic epidermal necrolysis in adults

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Basic aspects of the pathogenesis and prevention of non-melanoma skin cancer in solid organ transplant recipients: a review

Abstract

Introduction

As numbers of transplant recipients and survival rates increase, the vulnerability of this population to several malignancies also rises. Non-melanoma skin cancer (NMSC) carries the highest rates of morbidity and mortality in this population. To avoid these malignancies, it is necessary to identify particular risk factors in transplant recipients and to follow preventive protocols.

Methods

The MEDLINE and EMBASE databases were reviewed using as keywords the medical subject headings (MeSH) "transplantation", "skin neoplasm" and "prevention". The search was limited to clinical trials, randomized clinical trials and case–control studies conducted during the previous 20 years.

Results

The most important risk factors for the development of NMSCs in the transplant recipient population are cumulative ultraviolet radiation exposure, use of immunosuppressive agents (especially azathioprine as a photosensitizing agent) and infections by human papillomaviruses. The use of sun protection and retinoids were identified as possible protective factors. Other potential therapies, such as antioxidants, difluormethylornithine and cyclooxygenase-2 inhibitors, require further study.

Conclusions

Patient risk factors for the development of NMSC should be reviewed during the transplant consultation. Individuals found to be at increased risk should undergo closer follow-up and preventive care counseling. This article proposes an algorithm for the prevention of NMSC.

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Muir–Torre syndrome: multiple sebaceous neoplasms and visceral malignancy manifesting after cardiac transplantation and iatrogenic immunosuppression

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The use of intravenous immunoglobulins in Stevens–Johnson syndrome and toxic epidermal necrolysis: caution needed

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Bioengineering pediatric scaffold-free auricular cartilaginous constructs

Objective

The use of exogenous materials as scaffolds in cartilage tissue engineering has limited the clinical application of resultant constructs due to the risk of postoperative complications. In an effort to minimize such complications, we aim to generate human, scaffold-free auricular cartilaginous constructs.

Study Design

Laboratory study using pediatric auricular cartilage.

Methods

Remnant, normal pediatric auricular cartilage samples that would have otherwise been discarded were collected and digested to free cells. Harvested cells were cultured and expanded in vitro for two passages and plated as micromass cultures. The culture medium was replaced with a chemically defined chondrogenic medium, and cellular monolayers surrounding micromass cultures were continuously scraped off. Constructs were allowed to mature for a period of 8 weeks.

Results

Micromass constructs showed mechanical stability and structurally resembled native auricular tissue, with a perichondrium-like layer of cells surrounding the inner cartilaginous zone. Constructs accumulated equivalent sulphated glycosaminoglycan and 50% of collagen content compared to native auricular cartilage by mass, while displaying 156% more cellularity.

Conclusions

High-density micromass cultures of pediatric auricular chondrocytes can generate stable cartilaginous constructs following prolonged chondrogenic inductions in vitro. This technique is an essential step toward the development of three-dimensional constructs to recreate clinically applicable auricular cartilaginous constructs.

Level of Evidence

NA. Laryngoscope, 2016

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In response to regeneration of traumatic tympanic membrane perforation using EGF and FGF-2

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Impact of short sleep on metabolic variables in obese children with obstructive sleep apnea

Objectives/Hypothesis

To analyze the association between sleep duration, metabolic variables, and insulin resistance in obese children with and without obstructive sleep apnea. The decline in sleep duration has paralleled a dramatic increase in the prevalence of obesity and diabetes, suggesting a mechanistic relationship.

Study Design

Retrospective, case series.

Methods

Consecutive obese patients 3 to 12 years of age who underwent polysomnography (PSG) and a metabolic panel and who completed a 14-item sleep questionnaire were analyzed. All laboratory testing was conducted within 3 months of PSG. Total sleep times were obtained from the PSG and confirmed by the questionnaire.

Results

A total of 171 patients (55.0% male) were studied. All patients were obese (body mass index [BMI] z score > 95th percentile). Patients were categorized into three groups: short sleepers, borderline sleepers, and optimal sleepers. Eighty-six (50.3%) patients were short sleepers, 71 (41.5%) were borderline sleepers, and 14 (8.2%) were optimal sleepers. The mean BMI z score was 3.13 ± 1.3 in short sleepers, 3.3 ± 1.1 in borderline sleepers, and 3.5 ± 1.5 in optimal sleepers (P = .39). There was no statistical difference in high- and low-density lipoprotein levels (P = .21 and P = .76, respectively) and total cholesterol (P = .43) among subgroups. Triglycerides, blood glucose, insulin, and homeostasis model assessment–insulin resistance were significantly higher in short sleepers when compared to borderline or normal sleepers (P = .008, P < .001, P < .001, and P < .001, respectively).

Conclusions

Short sleep duration was correlated with alterations in metabolic variables and insulin resistance in obese patients. This raises concern for development of comorbid conditions that can persist into adulthood.

Level of Evidence

4 Laryngoscope, 2016

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IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis

Publication date: Available online 20 November 2016
Source:Clinical Immunology
Author(s): Deepak M.W. Balak, Martijn B.A. van Doorn, Robert D. Arbeit, Rianne Rijneveld, Erica Klaassen, Tim Sullivan, Julie Brevard, H. Bing Thio, Errol P. Prens, J. (Koos) Burggraaf, Robert Rissmann
BackgroundAberrant toll-like receptors (TLRs) 7, 8, and 9 activation by self-nucleic acids is implicated in immune-mediated inflammatory diseases (IMIDs) such as psoriasis. In preclinical IMID models, blocking TLR-activation reduced disease severity. IMO-8400 is a first-in-class, oligonucleotide-based antagonist of TLRs 7, 8, and 9. We evaluated the short-term safety and proof-of-concept for efficacy of IMO-8400 in a first-in-patient phase 2 trial.MethodsForty-six psoriasis patients were randomly assigned to IMO-8400 in four dose levels or placebo for 12weeks. Post-treatment follow-up was seven weeks. Primary outcome was incidence of adverse events. Secondary, exploratory outcomes included changes in psoriasis area and severity index (PASI).ResultsIMO-8400 across all dose levels did not cause any serious or severe adverse events. The most common treatment-related adverse events were dose-dependent injection-site reactions. All IMO-8400 groups showed clinical improvement, but a clear dose-response relationship and statistically significant differences with placebo were not observed (P=0.26). Eleven (38%) of 29 subjects on IMO-8400 achieved ≥50% PASI-reduction, compared to 1 (11%) of 9 subjects on placebo. Five (17%) and 2 (7%) IMO-8400-treated subjects achieved PASI-75 and PASI-90, respectively, compared to none on placebo.ConclusionsShort-term IMO-8400-treatment was well tolerated and reduced psoriasis severity. These findings warrant further investigation of endosomal TLR-antagonism as a therapeutic approach in psoriasis and other TLR-mediated IMIDs.Trial registrationEudraCT 2013-000164-28 and Clinicaltrials.govNCT01899729.



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Neutrophil infiltration mediated by CXCL5 accumulation in the laryngeal squamous cell carcinoma microenvironment: A mechanism by which tumour cells escape immune surveillance

Publication date: Available online 19 November 2016
Source:Clinical Immunology
Author(s): Duo Zhang, Jian Zhou, Di Tang, Lin Zhou, Liang Chou, Kuang-yen Chou, Lei Tao, Li-ming Lu
The CXCL5 chemokine is important for neutrophil accumulation in tumour tissues. In this report, we attempted to clarify whether and how infiltrating tumour-associated neutrophils (TANs) in laryngeal squamous cell carcinoma (LSCC) affect the proliferation and activation of T cells. We examined chemokine expression by real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) and performed an immunohistochemical analysis of LSCC microarrays. The relationship between CXCL5 and CD66b (a neutrophil marker) was investigated by immunofluorescence staining. We found that CXCL5 was upregulated in LSCC tissues, whereas CXCL5 levels were decreased in LSCC patient serum. Furthermore, high levels of CXCL5 were significantly correlated with intratumoural neutrophil infiltration. Compared with peripheral blood neutrophils (PBNs), TANs significantly inhibited T cell proliferation and decreased IFN-γ and TNF-α secretion. These data suggest that excessive neutrophil infiltration is associated with advanced clinical stages of LSCC (T3 or T4, III or IV, and N1 or N2).



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Giving Tuesday is November 29th

Help the ATA to continue solving the puzzle of thyroid disease and thyroid cancer by
donating on #GivingTuesday to fund thyroid research and thyroid awareness

The post Giving Tuesday is November 29th appeared first on American Thyroid Association.

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Onset of psoriatic arthritis associated with multiple wasp stings

Hymenoptera stings have been incriminated as a cause of beekeeper's arthritis, a form of arthritis closely mimicking osteoarthritis. Inflammatory mediators in Hymenoptera venom, such as mastoparan, may activate phospholipase A2 (PLA2), which could contribute to the development of psoriatic arthritis (PsA). However, there are no documented cases of Hymenoptera stings associated with the onset of PsA. We present a case of multiple wasp stings temporally associated with the onset of PsA in a 46-year-old man.

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Fate of deoxynivalenol and deoxynivalenol-3-glucoside during cereal-based thermal food processing: a review study

Abstract

Deoxynivalenol (DON), the most commonly occurring trichothecene in nature, may affect animal and human health through causing diarrhea, vomiting, gastrointestinal inflammation, and immunomodulation. DON-3-glucoside (DON-3G) as a major plant metabolite of the mycotoxin is another "emerging" food safety issue in recent years. Humans may experience potential health risks by consuming DON-contaminated food products. Thus, it is crucial for human and animal health to study also the degradation of DON and DON-3G during thermal food processing. Baking, boiling, steaming, frying, and extrusion cooking are commonly used during thermal food processing and have promising effects on the reduction of mycotoxins in food. For DON, however, the observed effects of these methods, as reported in numerous studies, are ambiguous and do not present a clear picture with regard to reduction or transformation. This review summarized the influence of thermal processing on the stability of DON and the formation of degradation/conversion products. Besides this, also a release of DON and DON-3G from food matrix as well as the release of DON from DON-3G during processing is discussed. In addition, some conflicting findings as reported from the studies on thermal processing as well as cause-effect relationships of the different thermal procedures are explored. Finally, the potential toxic profiles of DON degradation products are discussed as well when data are available.

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Beneficial effects of Galectin-9 on allergen-specific sublingual immunotherapy in a Dermatophagoides farinae-induced mouse model of chronic asthma

Publication date: Available online 19 November 2016
Source:Allergology International
Author(s): Masaki Ikeda, Shigeki Katoh, Hiroki Shimizu, Akira Hasegawa, Katsuyo Ohashi-Doi, Mikio Oka
BackgroundAllergen-specific sublingual immunotherapy is a potential disease-modifying treatment for allergic asthma. Galectin-9 (Gal-9), a β-galactoside-binding protein with various biologic effects, acts as an immunomodulator in excessive immunologic reactions by expanding regulatory T cells (Treg) and enhancing transforming growth factor (TGF)-β signaling. We investigated the efficacy of sublingually administered Gal-9 as an adjuvant to a specific allergen in a Dermatophagoides farinae (Df)-induced mouse model of chronic asthma.MethodsBALB/c mice were intranasally sensitized with Df extract 5 days/week for 5 weeks, and then sublingual Df-allergen extract for 2 weeks (5 days/week). Three days after the final sublingual treatment, mice were intranasally challenged with Df extract. The early asthmatic response (EAR) was evaluated 5 min after the last Df challenge. Airway hyperresponsiveness (AHR) was assayed and bronchoalveolar lavage (BAL) was performed 24 h after the last allergen challenge. Serum IgE and cytokine levels, and number of inflammatory cells in the BAL fluid (BALF) were analyzed.ResultsSublingual Df treatment in the presence of Gal-9, but not alone, significantly reduced AHR; EAR; number of eosinophils and interleukin-13 in the BALF; and serum IgE levels. BALF TGF-β1 levels were significantly increased in the presence of Gal-9 compared with Df alone. Treg depletion blocked the inhibitory effects of Gal-9 on the EAR, AHR, eosinophilic airway inflammation, and Df-specific serum IgE levels, and suppressed BALF TGF-β1 levels.ConclusionsGal-9 exhibited beneficial effects of sublingual Df allergen-specific immunotherapy in a Df-induced mouse model of chronic asthma, possibly by Gal-9-induced TGF-β1 production in the lung.



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Reduction or discontinuation of antipsychotics for challenging behaviour in adults with intellectual disability: a systematic review.

Sheehan, R; Hassiotis, A; (2016) Reduction or discontinuation of antipsychotics for challenging behaviour in adults with intellectual disability: a systematic review. Lancet Psychiatry 10.1016/S2215-0366(16)30191-2 .

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Thermodynamics-based Metabolite Sensitivity Analysis in Metabolic Networks.

Kiparissides, A; Hatzimanikatis, V; (2016) Thermodynamics-based Metabolite Sensitivity Analysis in Metabolic Networks. Metab Eng 10.1016/j.ymben.2016.11.006 .

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Neurite Orientation Dispersion and Density Imaging (NODDI) in Young Onset Alzheimer's Disease and Its Syndromic Variants

Zhang, J; Slattery, CATHERINE; Paterson, ROSS; Foulkes, ALEXANDER; Mancini, LAURA; Thomas, DAVID; Modat, MARC; Zhang, J; Slattery, CATHERINE; Paterson, ROSS; Foulkes, ALEXANDER; Mancini, LAURA; Thomas, DAVID; Modat, MARC; Toussaint, NICOLAS; Cash, DAVID; Thornton, JOHN; Alexander, DANIEL; Ourselin, SEBASTIEN; Fox, NICK; Schott, JONATHAN; Zhang, HUI; - view fewer (2016) Neurite Orientation Dispersion and Density Imaging (NODDI) in Young Onset Alzheimer's Disease and Its Syndromic Variants. In:

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Strategies for synthesis of epoxy resins from oleic acid derived from food wastes

Hayes, T; Hu, Y; Sanchez-Vazquez, SA; Hailes, HC; Aliev, AE; Evans, JRG; (2016) Strategies for synthesis of epoxy resins from oleic acid derived from food wastes. JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY , 54 (19) pp. 3159-3170. 10.1002/pola.28203 .

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Common methods of measuring 'informed choice' in screening participation: Challenges and future directions.

Ghanouni, A; Renzi, C; Meisel, SF; Waller, J; (2016) Common methods of measuring 'informed choice' in screening participation: Challenges and future directions. Prev Med Rep , 4 pp. 601-607. 10.1016/j.pmedr.2016.10.017 .

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Patient eligibility for anti-fibrotic therapy in idiopathic pulmonary fibrosis can be altered by use of different sets of reference values for calculation of FVC percent predicted.

Ward, K; Spurr, L; Goldman, NR; Margaritopoulos, GA; Kokosi, M; Renzoni, E; Chua, F; Ward, K; Spurr, L; Goldman, NR; Margaritopoulos, GA; Kokosi, M; Renzoni, E; Chua, F; Maher, TM; Ward, S; Wells, AU; - view fewer (2016) Patient eligibility for anti-fibrotic therapy in idiopathic pulmonary fibrosis can be altered by use of different sets of reference values for calculation of FVC percent predicted. Respir Med , 120 pp. 131-133. 10.1016/j.rmed.2016.10.007 .

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Blood-based Diagnosis of Idiopathic Pulmonary Fibrosis. Fantasy or Reality?

Maher, TM; (2016) Blood-based Diagnosis of Idiopathic Pulmonary Fibrosis. Fantasy or Reality? Am J Respir Crit Care Med , 194 (10) pp. 1182-1184. 10.1164/rccm.201606-1128ED .

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