Hold your horses: A comparison of human laryngomalacia with analogous equine airway pathology

Publication date: February 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 105
Author(s): Rachael J. Lawrence, Matthew J. Butterell, James D. Constable, Matija Daniel
ObjectivesLaryngomalacia is the most common cause of stridor in infants. Dynamic airway collapse is also a well-recognised entity in horses and an important cause of surgical veterinary intervention. We compare the aetiology, clinical features and management of human laryngomalacia with equine dynamic airway collapse.MethodsA structured review of the PubMed, the Ovid Medline and the Cochrane Collaboration databases (Cochrane Central Register of Controlled Trials, Cochrane Database of Systemic Reviews).ResultsThere are numerous equine conditions that cause dynamic airway collapse defined specifically by the anatomical structures involved. Axial Deviation of the Aryepiglottic Folds (ADAF) is the condition most clinically analogous to laryngomalacia in humans, and is likewise most prevalent in the immature equine airway. Both conditions are managed either conservatively, or if symptoms require it, with surgical intervention. The operative procedures performed for ADAF and laryngomalacia are technically comparable.ConclusionDynamic collapse of the equine larynx, especially ADAF, is clinically similar to human laryngomalacia, and both are treated in a similar fashion.



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Priorities for future research into asthma diagnostic tools: A PAN-EU Consensus exercise from the European asthma research innovation partnership (EARIP)

Abstract

The diagnosis of asthma is currently based on clinical history, physical examination and lung function; and to date there are no accurate objective tests either to confirm the diagnosis or to discriminate between different types of asthma. This consensus exercise reviews the state-of-the-art in asthma diagnosis to identify opportunities for future investment based on the likelihood of their successful development, potential for widespread adoption and their perceived impact on asthma patients.

Using a two-stage e-Delphi process and a summarising workshop, a group of European asthma experts including health professionals, researchers, people with asthma and industry representatives ranked the potential impact of research investment in each technique or tool for asthma diagnosis and monitoring. After a systematic review of the literature, 21 statements were extracted and were subject of the two-stage Delphi process. Eleven statements were scored 3 or more and were further discussed and ranked in a face to face workshop.

The three most important diagnostic/predictive tools ranked were: "New biological markers of asthma (e.g. genomics, proteomics and metabolomics) as a tool for diagnosis and/or monitoring", "Prediction of future asthma in preschool children with reasonable accuracy" and "Tools to measure volatile organic compounds (VOCs) in exhaled breath".

This article is protected by copyright. All rights reserved.

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Overexpression of sprouty2 in human oral squamous cell carcinogenesis

Publication date: March 2018
Source:Archives of Oral Biology, Volume 87
Author(s): Pei-Hsien Liao, Yen-Yun Wang, Wen-Chen Wang, Chung-Ho Chen, Yu-Hsun Kao, Jing-Wei Hsu, Ching-Yi Chen, Ping-Ho Chen, Shyng-Shiou Yuan, Yuk-Kwan Chen
ObjectiveThis study investigated SPRY2 expression in human oral potentially malignant disorders (OPMDs) and oral squamous cell carcinomas (OSCCs).Methods75 OSCCs, 23 OPMDs with malignant transformation (MT), 17 OPMDs without MT, and eight normal oral mucosa (NOM) tissues were used for immunohistochemical staining; three OSCC tissues with normal tissue counterparts were used for western blotting. Three human oral cancer cell lines (OCCLs), an oral precancer cell line (DOK), and a NOM primary culture (NOMPC) were used for western blotting; OCCLs and NOMPC were employed for real-time quantitative reverse transcription-polymerase chain reaction. OCCLs were evaluated in terms of proliferation, migration, invasion and BRAF V600E point mutation assays.ResultsSignificantly increased SPRY2 protein expression was observed in OSCCs as compared with NOM, and SPRY2 expression also differed between OSCC patients with and without lymph-node metastasis. SPRY2 protein and mRNA expressions were significantly enhanced as compared with NOMPC. Increased phospho-ERK expression was observed in OCCLs as compared with NOMPC. Significant decreases in the proliferation rate, degrees of migration and invasion were noted in OCCLs with SPRY2 siRNA transfection as compared with those without SPRY2 siRNA transfection. No BRAF V600E point mutation was observed for OCCLs as compared with NOMPC. A significantly increased SPRY2 protein level was noted in OPMDs with MT as compared to those without MT, and was also found in OPMDs with MT in comparison with NOM, as well as in DOK in comparison with NOMPC.ConclusionsOur results indicated that SPRY2 overexpression is associated with human oral squamous-cell carcinogenesis.



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Superhydrophilic co-polymer coatings on denture surfaces reduce Candida albicans adhesion—An in vitro study

Publication date: March 2018
Source:Archives of Oral Biology, Volume 87
Author(s): Masahiro Hirasawa, Chiaki Tsutsumi-Arai, Kensuke Takakusaki, Toyohisa Oya, Kenji Fueki, Noriyuki Wakabayashi
ObjectiveIn this study, we aimed to investigate denture-base-resin coatings prepared with a crosslinkable co-polymer containing sulfobetaine methacrylamide (SBMAm) and the relationship between their surface characteristics and the initial adhesion of Candida albicans (C. albicans).MethodsAcrylic resin discs were coated with co-polymers containing various concentrations of SBMAm and N,N'-(4,7,10-trioxa-1,13-tridecadiamine) diacrylamide (JDA) as crosslinking agent. Uncoated discs were used as controls. An acquired pellicle was formed on each disc using artificial saliva, and the discs were immersed in a suspension of C. albicans (JCM2085) cells. After incubation, tetrazolium salt (XTT-reduction) and colony forming unit (CFU) assays were performed and the morphogenesis of C. albicans was examined using scanning electron microscopy (SEM). The surface roughness, film thickness, and the water contact angle of each disc surface were measured.ResultsAll coating groups showed significantly lower amounts of adhered C. albicans in the XTT-reduction and CFU assays than the control, confirmed by the SEM images. Many wrinkle structures were observed on the surfaces coated with co-polymers containing more than 30% SBMAm. There were no significant differences in surface roughness among all groups. The co-polymer films on the coated discs were less than 5.0 μm in thickness, and these surfaces exhibited significantly lower mean water contact angles than the control.ConclusionCrosslinkable co-polymers containing SBMAm can enhance the hydrophilicity of the surface of denture-base resins and reduce the initial adhesion of C. albicans.



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Immunoexpression of proteins involved in cytoskeleton remodeling in benign odontogenic lesions

Publication date: March 2018
Source:Archives of Oral Biology, Volume 87
Author(s): Paula Nascimento Antonio, Natália Galvão Garcia, Agnes Assao, José Roberto Pereira Lauris, Fernando Augusto Soares, Denise Tostes Oliveira
ObjectiveThe present study was designed to analyze the immunolocalization of proteins involved in cytoskeleton remodeling, such as moesin and Rho-A, in benign odontogenic lesions that present with expansive growth and invasive clinical behavior.Materials and methodsExpressions of moesin and Rho-A in odontogenic epithelium were evaluated by immunohistochemical analysis in 45 odontogenic lesions using monoclonal antibodies.ResultsOur results demonstrated strong membranous and cytoplasmic expressions of moesin in the epithelial cells in 66.7% and 44.4% of the odontogenic lesions, respectively. Furthermore, Rho-A expression in odontogenic epithelium was strong in the membrane and cytoplasm of 51.1% and 62.2% of the odontogenic lesions, respectively. A statistically significant correlation was found between the membranous and cytoplasmic expressions of moesin (p = 0.000) and those of Rho-A (p = 0.048) in odontogenic epithelial cells, while no statistically significant correlation was found between moesin and Rho-A expressions (p > 0.05).ConclusionsThe present study confirmed the strong expressions of moesin and Rho-A by odontogenic epithelial cells, suggesting their involvement in the development of benign odontogenic lesions. However, this study has failed to detect the connection between the moesin and Rho-A interaction in expansive growth and local invasiveness of these lesions.



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Surgical management of pulsatile tinnitus secondary to jugular bulb or sigmoid sinus diverticulum with review of literature

Publication date: Available online 29 December 2017
Source:American Journal of Otolaryngology
Author(s): W.X. Yeo, S.H. Xu, T.Y. Tan, Y.M. Low, H.W. Yuen
IntroductionJugular bulb and sigmoid sinus anomalies are well-known causes of vascular pulsatile tinnitus. Common anomalies reported in the literature include high-riding and/or dehiscent jugular bulb, and sigmoid sinus dehiscence. However, cases of pulsatile tinnitus due to diverticulosis of the jugular bulb or sigmoid sinus are less commonly encountered, with the best management option yet to be established. In particular, reports on surgical management of pulsatile tinnitus caused by jugular bulb diverticulum have been lacking in the literature.ObjectivesTo report two cases of pulsatile tinnitus with jugular bulb and/or sigmoid sinus diverticulum, and their management strategies and outcomes. In this series, we describe the first reported successful case of pulsatile tinnitus due to jugular bulb diverticulum that was surgically-treated.Subjects and methodsTwo patients diagnosed with either jugular bulb and/or sigmoid sinus diverticulum, who had presented to the Otolaryngology clinic with pulsatile tinnitus between 2016 and 2017, were studied. Demographic and clinical data were obtained, including their management details and clinical outcomes.ResultsTwo cases (one with jugular bulb diverticulum and one with both sigmoid sinus and jugular bulb diverticula) underwent surgical intervention, and both had immediate resolution of pulsatile tinnitus post-operatively. This was sustained at subsequent follow-up visits at the outpatient clinic, and there were no major complications encountered for both cases intra- and post-operatively.ConclusionTransmastoid reconstruction/resurfacing of jugular bulb and sigmoid sinus diverticulum with/without obliteration of the diverticulum is a safe and effective approach in the management of bothersome pulsatile tinnitus arising from these causes.



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Introduction: Antibody-Mediated Therapy Special Issue Part 2

Antibodies have been used therapeutically for well over a century but the breadth and depth of their applications are increasing so rapidly and successfully that clinical studies are informing mechanistic questions while basic research continues to interrogate how antibodies are made and function, so their properties can be further refined. The first part of this Special Issue comprised five review articles (1); this second part includes four more reviews. Once again, we thank the authors for their excellent contributions. This issue also includes an original research article that builds on observations from patients with hyper-IgM syndrome to further define the mechanism for antibody class-switch recombination (CSR).

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Cover

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Table of Contents

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A pro-inflammatory role of Fcα/μR on marginal zone B cells in sepsis

Abstract

Fc receptors play important roles for a wide array of immune responses. In contrast to the well-defined Fcγ and Fcε receptors, the molecular and functional characteristics of Fc receptors for IgA and IgM have remained incompletely understood for years. Recent progress has unveiled the characteristics of Fc receptors for IgA and IgM, including Fcα/μ receptor (Fcα/μR) (CD351), polymeric immunoglobulin receptor (poly-IgR), Fcα receptor (FcαRI) (CD89) and Fcμ receptor (FcμR). In this review, we summarize the molecular and functional characteristics of Fcα/μR in comparison with poly-IgR, FcμR and FcαRI, and focus particularly on the pro-inflammatory function of Fcα/μR expressed on marginal zone B cells in sepsis.

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Depletion of recombination-specific cofactors by the C-terminal mutant of the activation-induced cytidine deaminase causes the dominant negative effect on class switch recombination

Abstract

Activation-induced cytidine deaminase (AID) is essential for class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes. Studies on in vitro mutagenized AID as well as its mutations in human patients with hyper-IgM (HIGM)-syndrome type II revealed that C-terminal AID mutations were defective in CSR whereas their DNA cleavage and SHM activities remained intact. The C-terminal mutants of AID were speculated to exert the dominant negative effect on wild-type (WT) AID whereas its mechanism remains unknown. We generated the JP41 (R190X) mutation in one allele and a null mutation on the other allele in a mouse B cell line (CH12F3-2A) using CRISPR/Cas9 genome-editing tools and studied the effect of JP41 expression on the function of exogenously introduced WT AID fused with estrogen receptor (AIDER) in AID^JP41/∆/AIDER CH12F3-2A cells. We found that JP41 expression strongly suppressed not only CSR but also Igh/c-Myc chromosomal translocations by AIDER. We showed that the dominant negative effect is not evident at the DNA cleavage step but obvious at both deletional and inversional recombination steps. We also confirmed the dominant negative effect of other C-terminal mutants, JP8Bdel (R183X) and P20 (34-aa insertion at residue 182) in AID-deficient spleen B cells. Finally, we showed that the expression of JP41 reduced the binding of AIDER with its cofactors (hnRNP L, SERBP1 and hnRNP U). Together, these data indicate that dominant negative effect of JP41 on CSR is likely due to the depletion of the CSR-specific RNA-binding proteins from WT AID.

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Targeted antibody therapy and relevant novel biomarkers for precision medicine for rheumatoid arthritis

Abstract

Over the past two decades, the management of rheumatoid arthritis (RA) has progressed remarkably, encompassing the development of new diagnostic tools and efficacious biological agents, such as monoclonal antibodies against inflammatory cytokines and surface markers on immune cells. In addition to the significant efficacy of these biological agents, biomarkers for RA are under consideration for their potential to classify heterogeneous patients into several groups based on clinical and immunological phenotypes for the prediction of clinical course and prognosis and the facilitation of appropriate and precise treatment with the appropriate therapeutic monoclonal antibodies. Biomarkers, particularly those for the prediction and monitoring of the responses to therapeutic monoclonal antibodies for RA, are in demand, with many approaches examined in recent years. In this article, we have summarized the background research on biomarkers and introduced recent topics in the field that enable the possible clinical applications of biomarkers, especially those related to pathogenic cytokines, to guide the treatment of RA.

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Sweet SIGNs: IgG glycosylation leads the way in IVIG-mediated resolution of inflammation

Abstract

A hallmark of many chronic inflammatory and autoimmune diseases is that there is an impaired resolution of inflammation and return to the steady state. The infusion of high doses of pooled serum IgG preparations from thousands of donors [intravenous immunoglobulin (IVIG) therapy] has been shown to induce resolution of inflammation in a variety of chronic inflammatory and autoimmune diseases, suggesting that IgG molecules can instruct the immune system to stop inflammatory processes and initiate the return to the steady state. The aim of this review is to discuss how insights into the mechanism of IVIG activity may help to understand the molecular and cellular pathways underlying resolution of inflammation. We will put a special emphasis on pathways dependent on the IgG F_C domain and IgG sialylation, as several recent studies have provided new insights into how this glycosylation-dependent pathway modulates innate and adaptive immune responses through different sets of C-type or I-type lectins.

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IVIG-mediated effector functions in autoimmune and inflammatory diseases

Abstract

Intravenous immunoglobulin (IVIG) is a pooled preparation of normal IgG obtained from several thousand healthy donors. It is widely used in the immunotherapy of a large number of autoimmune and inflammatory diseases. The mechanisms of action of IVIG are complex and, as discussed in this review, experimental and clinical data provide an indicator that the therapeutic benefit of IVIG therapy is due to several mutually non-exclusive mechanisms affecting soluble mediators as well as cellular components of the immune system. These mechanisms depend on Fc and/or F(ab′)₂ fragments. A better understanding of the effector functions of IVIG should help in identification of biomarkers of responses to IVIG in autoimmune patients.

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Barrier dysfunction in allergy

Publication date: January 2018
Source:Allergology International, Volume 67, Issue 1
Author(s): Kenji Kabashima, Kenji Izuhara




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Food Protein-Induced Proctocolitis. The shadow of allergic disorders

Publication date: January–February 2018
Source:Allergologia et Immunopathologia, Volume 46, Issue 1
Author(s): C.A. Sánchez-Salguero




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Type III interferons are critical host factors that determine susceptibility to Influenza A viral infection in allergic nasal mucosa

Abstract

Background

Allergic respiratory conditions have been associated with increased susceptibility to viral infection due to impaired interferon (IFN)-related immune responses but the mechanisms for reinforcement of mucosal immunity against viral infection in allergic diseases are largely unknown.

Objectives

To determine whether IFN induction would be impaired in allergic nasal mucosa and to identify if higher loads of influenza A virus (IAV) in allergic nasal mucosa could be controlled with IFN treatment.

Methods

IAV mRNA, viral titers and IFN expression were compared in IAV-infected normal human nasal epithelial (NHNE, N=10) and allergic rhinitis nasal epithelial (ARNE, N=10) cells. We used in vivo model of allergic rhinitis (BALB/C mouse, N=10) and human nasal mucosa from healthy volunteers (N=72) and allergic rhinitis patients (N=29) to assess the induction of IFNs after IAV infection.

Results

IAV mRNA levels and viral titers were significantly higher in ARNE compared with NHNE cells. IFN-β and -λs were induced in NHNE and ARNE cells up to 3 days after IAV infection. Interestingly, induction of IFN-λs mRNA levels and the amount of secreted proteins were considerably lower in ARNE cells. The mean IFN-λs mRNA level was also significantly lower in the nasal mucosa of AR patients and we found that recombinant IFN-λ treatment attenuated viral mRNA levels and viral titers in IAV-infected ARNE cells. In vivo AR mouse were exhibited higher viral load after IAV infection but intranasal inoculation of IFN-λ completely decreased IAV protein expression and viral titer in nasal mucosa of IAV-infected AR mouse.

Conclusion

Higher susceptibility of the allergic nasal mucosa to IAV may depend on impairment of type III IFN induction, and type III IFN is a key mechanistic link between higher viral loads and control of IAV infection in allergic nasal mucosa.

This article is protected by copyright. All rights reserved.

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Sex-based differences in CD103+ dendritic cells promote female-predominant Th2 cytokine production during allergic asthma

Abstract

Background

Gender disparities in adult patients with asthma regarding its prevalence and severity are mainly due to enhanced type 2 T-helper (Th2) cytokine production in female patients compared to that in male patients. However, the pathways mediating this effect remain unclear.

Objective

We aimed to determine the roles of two major subsets of dendritic cells (DCs) in females, specifically those displaying CD11b or CD103, during enhanced Th2-priming after allergen exposure, using an ovalbumin-induced asthma mouse model.

Methods

Sex-based differences in the number of DCs at inflamed sites, co-stimulatory molecule expression on DCs, and the ability of DCs to differentiate naïve CD4⁺ T cells into Th2 population were evaluated after allergen exposure in asthmatic mice. In addition, we assessed the role of 17β-estradiol in CD103⁺ DC function during Th2-priming in vitro.

Results

The number of CD11b^high DCs and CD103⁺ DCs in the lung and bronchial lymph node (BLN) were increased to a greater extent in female mice than in male mice at 16 to 20 hours after ovalbumin (OVA) inhalation. In BLNs, CD86 and I-A/I-E expression levels and antigen uptake ability in CD103⁺ DCs, but not in CD11b^high DCs, were greater in female mice than in male mice. Furthermore, CD4⁺ T cells cultured with CD103⁺ DCs from female mice produced higher levels of interleukin (IL)-4, IL-5, and IL-13, compared with CD4⁺ T cells cultured with CD103⁺ DCs from male mice. The 17β-estradiol oriented-enhancement of CD86 expression on CD103⁺ DCs after allergen exposure induced the enhanced IL-5 production from CD4⁺ T cells.

Conclusions & Clinical Relevance

These findings suggest that with regards to asthma, enhanced Th2 cytokine production in females might be attributed to 17β-estradiol-mediated Th2-oriented CD103⁺ DCs in the BLN.

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Different applicabilities of the etch-bleach-seal technique for treating opacities on permanent incisor damage by molar incisor hypomineralisation in three young patients

Enamel opacity on anterior teeth can be prejudicial for the aesthetic appearance of affected patients. Patients with molar incisor hypomineralisation, for example, present opacities that can range from discrete white mottling to extensive yellow-brown discolourations. They can request a treatment to improve their aesthetic conditions. Many techniques have been considered to manage this condition. Wright developed a technique called etch–bleach–seal, which showed promising results for the management of anterior enamel opacities. The aims of this report are to present this technique and to analyse its benefits and inconveniences.

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The effect of flurbiprofen oral spray and ibuprofen versus ibuprofen alone on postoperative tonsillectomy pain: an open randomised controlled trial

Abstract

Objective

This prospective clinical study was carried out to evaluate the analgesic efficacy and safety of oral spray form of flurpiprofen in the treatment of postoperative pain in tonsillectomy patients.

Study Design

Open randomised controlled clinical study.

Setting

Tertiary care training and research hospital.

Participants

One hundred (53 males, 47 females) with an age range of 18-53 years old (mean 27.4 ± 9.3 SD) undergoing tonsillectomy were enrolled to this prospective controlled study.

Main outcome measures

Patients receiving oral ibuprofen and flurbiprofen as spray form were enrolled as study group (53) whereas patients receiving only oral ibuprofen were enrolled as control group (47) in postoperative period. Postoperative pain was evaluated through visual analog scale on 12th hour, first, third and seventh days after surgery.

Results

The mean maximal pain score of patients who have received flurbiprofen spray and ibuprofen was 3.36 ± 1.93 SD that was statistically lower than the mean maximal pain score of patients who were medicated with only ibuprofen which was 4.06 ± 1.29 SD on postoperative seventh day (p=0.013).

Conclusion

This study revealed that addition of flurbiprofen spray to oral ibuprofen is effective in the management of postoperative pain in tonsillectomy patients with no notable complications.

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Cold/Cold vs. Bipolar Dissection Tonsillectomy: A Surgeon-Controlled Study of 400 Cases

Abstract

Surgeon controlled study of 200 cold/cold and 200 hot/hot tonsillectomy cases in one institution

Hot/hot resulted in higher overall rates of early and late post-tonsillectomy haemorrhage and return-to-theatre when compared to cold/cold methods.

Bipolar diathermy tonsillectomy resulted in a statistically significant higher rate of secondary post-tonsillectomy haemorrhage than cold-steel of nearly three times.

Trainee surgeons performed better in bipolar haemostasis than cold-steel dissection with regard to post-operative morbidity.

With continued use of cold-steel tonsillectomy methods in both junior and senior surgeons, it is hoped that the rates of PTH and RTT will continue to improve.

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Double Suspension Sutures: a simple Surgical Technique for Selected Cases of obstructive Sleep Apnea: our experience with twenty two patients

Abstract

This work aimed at presenting a simple modification of expansion pharyngoplasty using bilateral double palatal suspension sutures for the treatment of selected cases of snoring and OSA.

Between Marsh 2013 and August 2017, twenty- two patients underwent the double suspension sutures technique as a treatment for retropalatal collapse of obstructive sleep apnea.

Postoperatively, the mean AHI and the mean lowest oxygen saturation level showed highly significant improvement. Both the retropalatal and interpillar distances were increased significantly.

No persistent postoperative complications were reported. Snoring disappeared in 86.4% of patients.

The procedure is simple, well-tolerated by patients and reversible. It is an economic and less traumatic maneuver. It could be applied as a part of multilevel surgery.

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Autografting in the treatment of large, auricular keloids

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Jet ventilation in obese patients undergoing airway surgery for subglottic and tracheal stenosis

Objectives/Hypothesis

To assess the feasibility of jet ventilation in obese patients and to compare complications of jet ventilation in obese and nonobese patients.

Study Design

Retrospective review of medical records.

Methods

We reviewed 46 patient charts (70 procedures) with the diagnosis of tracheal or subglottic stenosis who underwent endoscopic surgery with jet ventilation between March 2014 and January 2017. Adequacy of jet ventilation was assessed by chest rise, avoidance of endotracheal intubation, and length of case and ventilation. Records were reviewed for demographic details, anesthesia records, and complications.

Results

In 29/70 (41.4%) of cases, patients were obese; in 9/29 (31.0%) of these cases, patients were morbidly obese. Jet ventilation was successful in 28/29 (97%) of obese cases. In 1/29 (3.4%) of cases, the patient required alternative airway management. There were no significant differences between obese and nonobese patients in chest rise, need for endotracheal intubation, and length of surgery or ventilation (P > .05). There were 2/29 (6.9%) cases of intra- and postoperative complications including laryngospasm (1/29, 3.4%) and tachycardia (1/29, 3.4%). Rate of complications did not differ between obese and nonobese patients (P = .178).

Conclusions

Jet ventilation in obese patients can be done successfully, and complications are similar between obese patients and nonobese patients.

Level of Evidence

4. Laryngoscope, 00:000–000, 2017

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