Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Δευτέρα 6 Φεβρουαρίου 2017

Topical tacrolimus, triamcinolone acetonide and placebo in oral lichen planus: A pilot randomized controlled trial

Abstract

Objective

To carry out a double-blind RCT to compare the effectiveness of topical tacrolimus (TAC), triamcinolone acetonide (TRI) and placebo (PLA) in symptomatic OLP.

Subjects and methods

A clinical score (CS, range 0-130) was developed to measure the clinical signs and symptoms of OLP. Twenty-seven OLP patients with a CS of ≥ 20 were randomly allocated to receive 0.1% TAC ointment (n=11), 0.1% TRI paste (n=7) or Orabase® paste as PLA (n=9) for 3 weeks. If the CS dropped ≥ 20% (interpreted as response), the patients continued the same medication for another 3 weeks. If the CS dropped < 20% or increased (non-response), the patients were switched to TAC for 6 weeks. A 6-month follow-up period ensued. The primary outcome variable was the change in CS from baseline to week 3. In primary outcome analysis, CS values between the treatment arms were compared.

Results

TAC and TRI were more effective (p=0.012 and 0.031, respectively) than PLA in reducing the CS at week 3. No difference in the efficacy was noted between TAC and TRI (p=0.997).

Conclusions

This pilot RCT provides evidence for the effectiveness of TAC and TRI over PLA in the management of OLP.

This article is protected by copyright. All rights reserved.



http://ift.tt/2ljtatH

Recent Updates on Electronic Cigarette Aerosol and Inhaled Nicotine Effects on Periodontal and Pulmonary Tissues

Abstract

E-cigarette derived inhaled nicotine may contribute to the pathogenesis of periodontal and pulmonary diseases in particular via lung inflammation, injurious and dysregulated repair responses. Nicotine is shown to have anti-proliferative properties and affects fibroblasts in vitro, which may interfere in tissue myofibroblast differentiation in e-cig users. This will affect the ability to heal wounds by decreasing wound contraction. In periodontics, direct exposure to e-vapor has been shown to produce harmful effects in periodontal ligament and gingival fibroblasts in culture. This is due to the generation of reactive oxygen species/aldehydes/carbonyls from e-cig aerosol, leading to protein carbonylation of extracellular matrix and DNA adducts/damage. A limited number of studies regarding the effects of e-cig in oral and lung health are available. However, no reports are available to directly link the deleterious effects on e-cigs, inhaled nicotine, and flavorings aerosol on oral periodontal and pulmonary health in particular to identify the risk of oral diseases by e-cigarettes and nicotine aerosols. This mini-review summarizes the recent perspectives on e-cigarettes including inhaled nicotine effects on several pathophysiological events, such as oxidative stress, DNA damage, innate host response, inflammation, cellular senescence, pro-fibrogenic and dysregulated repair, leading to lung remodeling, oral submucous fibrosis and periodontal diseases.

This article is protected by copyright. All rights reserved.



http://ift.tt/2le1TMz

Comparative Effectiveness of Treatment Choices for Graves' Hyperthyroidism: A Historical Cohort Study

Thyroid , Vol. 0, No. 0.


http://ift.tt/2kBOY3L

Biochemical Markers Reflecting Thyroid Function in Athyreotic Patients on Levothyroxine Monotherapy

access_free.gif

Thyroid , Vol. 0, No. 0.


http://ift.tt/2klLTq5

Response to: “If the Metabolic Winter Is Coming, When Will It Be Summer?” (Metab Syndr Relat Disord 2017;15:3)

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.


http://ift.tt/2klQIQj

The relationship between a dolichofacial morphology and bone adaptation of the articular tubercle

Publication date: Available online 6 February 2017
Source:Archives of Oral Biology
Author(s): J.H. Koolstra, M.C.M. Jongenburger, G.R. Landweer, N.M.B.K. Willems
ObjectivesAgainst the background of a possibly compromised functional adaptation, the relationship between the height of the articular tubercle was analyzed as a function of the amount of divergence between the maxilla and the mandible.DesignThese parameters were obtained retrospectively from orthopantomograms and lateral radiographs produced in a standard procedure before orthodontic treatment.ResultsThe height of the articular tubercle appeared to be significantly smaller in a group of patients with a dolichofacial morphology, with respect of those with an average (mesofacial) morphology. Furthermore, there was a significant correlation between the height of the articular tubercle and the mandibular angle.ConclusionsThese results suggest that bone remodeling in selected parts of the orofacial skeleton can be compromised giving rise to an altered craniofacial morphology.



http://ift.tt/2jWxvpC

Differential human Th22-lymphocyte response triggered by Aggregatibacter actinomycetemcomitans serotypes

alertIcon.gif

Publication date: Available online 6 February 2017
Source:Archives of Oral Biology
Author(s): Jaime Díaz-Zúñiga, Samanta Melgar-Rodríguez, Gustavo Monasterio, Myriam Pujol, Leticia Rojas, Carla Alvarez, Paola Carvajal, Rolando Vernal
Objective: In Aggregatibacter actinomycetemcomitans, different serotypes have been described based on lipopolysaccharide (LPS) antigenicity. When T lymphocytes were stimulated with these serotypes, different patterns of T-helper (Th)1 and Th17-type of immune responses were reported. Recently, two new Th phenotypes have been described and named Th9 and Th22 lymphocytes; however, their role in the pathogenesis of periodontitis remains unclear. This study aimed to investigate the potential Th9 and/or Th22 lymphocyte responses when stimulated with autologous dendritic cells infected with different A. actinomycetemcomitans serotypes.MethodsMonocyte-derived dendritic cells and naïve CD4+ T lymphocytes were obtained from healthy donors and stimulated with different serotypes of A. actinomycetemcomitans at a multiplicity of infection MOI=102 or their purified LPS (10–50ng/ml). The levels for the Th9 and Th22-associated cytokines, as well as the transcription factor master-switch genes implied in their differentiation Spi-B and AhR, were quantified by qPCR and ELISA.ResultsWhen stimulated with the serotype b of A. actinomycetemcomitans, higher levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were detected in dendritic cells, as well as higher levels of IL-22 and AhR were detected in T lymphocytes, when compared with stimulation with the other serotypes.ConclusionsThe serotype b of A. actinomycetemcomitans has a higher capacity of trigger Th22-type of immune response in both dendritic cells and T lymphocytes. These data allow us to suggest that, when the serotype b of A. actinomycetemcomitans is a significant part of the subgingival biofilm, the Th22 polarization might be triggered within the periodontal lesion.



http://ift.tt/2kg5cyQ

Analysis of the Expression of NLRP3 and AIM2 in Periapical Lesions with Apical Periodontitis and Microbial Analysis Outside the Apical Segment of Teeth

Publication date: Available online 6 February 2017
Source:Archives of Oral Biology
Author(s): Shujun Ran, Bin Liu, Shensheng Gu, Zhe Sun, Jingping Liang
ObjectiveTo detect the distribution and expression levels of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and the absent in Melanoma 2 (AIM2) inflammasomes in periapical lesions and to analyse the possible microbial stimuli outside of teeth.DesignThe distribution of NLRP3 and AIM2 inflammasomes in sixteen periapical lesions was investigated by immunohistochemistry. Meanwhile, the relative gene expression levels of NLRP3 and AIM2 in sixteen periapical lesions and three health periodontal tissue were quantified by real-time polymerase chain reaction (PCR). Moreover, forty-seven teeth without sinus tracts were obtained in the clinic and included in bacterial analysis using PCR. Then, the mRNA levels of apoptosis-associated speck-like protein (ASC), caspase-1, interleukin-1β (IL-1β), NLRP3 and AIM2 in THP-1-derived macrophages treated with lipopolysaccharides (LPS) of Porphyromonas were also quantified by real-time PCR, and the IL-1β secretion level was investigated using enzyme-linked immunosorbent assay (ELISA).ResultsNLRP3 and AIM2 were positively expressed in periapical lesions and were mainly distributed in inflammatory cells. Most of the samples that demonstrated up-regulation of NLRP3 mRNA also demonstrated up-regulation of caspase-1 mRNA. Microbial analysis revealed that Porphyromonas endodontalis was the most commonly detected species and was detected in 27 of 47 cases (57.4%), followed by Fusobacterium nucleatum (20/47, 42.6%), Porphyromonas gingivalis (19/47, 40.4%), Tannerella forsythia (19/47, 40.4%), Actinomyces sp (17/47, 36.17%), Treponema denticola (10/47,21.28%), Actinomyces israelii (9/47,19.15%), Prevotella intermedia (6/47, 12.77%), Enterococcus faecalis (1/47,2.13%) and Enterococcus faecium (0/47,0). Furthermore, we found that LPS of P. gingivalis induced THP-1 cells to produce IL-1β and to activate NLRP3 and AIM2 inflammasomes.ConclusionsOur results suggest that the NLRP3 and AIM2 proteins play a part in the pathogenesis of periapical periodontitis. Anaerobes, such as P. endodontalis, P. gingivalis, F. nucleatum and T. forsythia, were the main detected microbial stimuli that activate inflammasomes in periapical tissues.



http://ift.tt/2jWmOUa

Increased melatonin in oral mucosal tissue of oral lichen planus (OLP) patients: A possible link between melatonin and its role in oral mucosal inflammation

alertIcon.gif

Publication date: Available online 6 February 2017
Source:Archives of Oral Biology
Author(s): Kirawut Luengtrakoon, Worraned Wannakasemsuk, Vilasinee Vichitrananda, Poramaporn Klanrit, Doosadee Hormdee, Rajda Noisombut, Ponlatham Chaiyarit
ObjectiveThe existence of extra-pineal melatonin has been observed in various tissues. No prior studies of melatonin in human oral mucosal tissue under the condition of chronic inflammation have been reported. The aim of this study was to investigate the presence of melatonin in oral mucosal tissue of patients with oral lichen planus (OLP) which was considered as a chronic inflammatory immune-mediated disease causing oral mucosal damage and ulcerations.Materials and methodsSections from formalin-fixed and paraffin-embedded oral mucosal tissue of OLP patients (n=30), and control subjects (n=30) were used in this study. Immunohistochemical staining was performed and the semiquantitative scoring system was used to assess the levels of arylalkylamine-N-acetyltransferase (AANAT: a rate-limiting enzyme in the biosynthesis pathway of melatonin), melatonin, and melatonin receptor 1 (MT1) in oral mucosa of OLP patients and normal oral mucosa of control subjects.ResultsAANAT, melatonin, and MT1were detected in oral mucosal tissue of OLP patients and control subjects. Immunostaining scores of AANAT, melatonin, and MT1 in oral mucosal tissue of OLP patients were significantly higher than those in control subjects (p=0.002, p < 0.001, and p=0.031, respectively).ConclusionsIncreased levels of AANAT, melatonin, and MT1 in the inflamed oral mucosal tissue of OLP patients imply that chronic inflammation may induce the local biosynthesis of melatonin via AANAT, and may enhance the action of melatonin via MT1.



http://ift.tt/2kg5nKe

The relationship between a dolichofacial morphology and bone adaptation of the articular tubercle

Publication date: Available online 6 February 2017
Source:Archives of Oral Biology
Author(s): J.H. Koolstra, M.C.M. Jongenburger, G.R. Landweer, N.M.B.K. Willems
ObjectivesAgainst the background of a possibly compromised functional adaptation, the relationship between the height of the articular tubercle was analyzed as a function of the amount of divergence between the maxilla and the mandible.DesignThese parameters were obtained retrospectively from orthopantomograms and lateral radiographs produced in a standard procedure before orthodontic treatment.ResultsThe height of the articular tubercle appeared to be significantly smaller in a group of patients with a dolichofacial morphology, with respect of those with an average (mesofacial) morphology. Furthermore, there was a significant correlation between the height of the articular tubercle and the mandibular angle.ConclusionsThese results suggest that bone remodeling in selected parts of the orofacial skeleton can be compromised giving rise to an altered craniofacial morphology.



http://ift.tt/2jWxvpC

Differential human Th22-lymphocyte response triggered by Aggregatibacter actinomycetemcomitans serotypes

alertIcon.gif

Publication date: Available online 6 February 2017
Source:Archives of Oral Biology
Author(s): Jaime Díaz-Zúñiga, Samanta Melgar-Rodríguez, Gustavo Monasterio, Myriam Pujol, Leticia Rojas, Carla Alvarez, Paola Carvajal, Rolando Vernal
Objective: In Aggregatibacter actinomycetemcomitans, different serotypes have been described based on lipopolysaccharide (LPS) antigenicity. When T lymphocytes were stimulated with these serotypes, different patterns of T-helper (Th)1 and Th17-type of immune responses were reported. Recently, two new Th phenotypes have been described and named Th9 and Th22 lymphocytes; however, their role in the pathogenesis of periodontitis remains unclear. This study aimed to investigate the potential Th9 and/or Th22 lymphocyte responses when stimulated with autologous dendritic cells infected with different A. actinomycetemcomitans serotypes.MethodsMonocyte-derived dendritic cells and naïve CD4+ T lymphocytes were obtained from healthy donors and stimulated with different serotypes of A. actinomycetemcomitans at a multiplicity of infection MOI=102 or their purified LPS (10–50ng/ml). The levels for the Th9 and Th22-associated cytokines, as well as the transcription factor master-switch genes implied in their differentiation Spi-B and AhR, were quantified by qPCR and ELISA.ResultsWhen stimulated with the serotype b of A. actinomycetemcomitans, higher levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were detected in dendritic cells, as well as higher levels of IL-22 and AhR were detected in T lymphocytes, when compared with stimulation with the other serotypes.ConclusionsThe serotype b of A. actinomycetemcomitans has a higher capacity of trigger Th22-type of immune response in both dendritic cells and T lymphocytes. These data allow us to suggest that, when the serotype b of A. actinomycetemcomitans is a significant part of the subgingival biofilm, the Th22 polarization might be triggered within the periodontal lesion.



http://ift.tt/2kg5cyQ

Analysis of the Expression of NLRP3 and AIM2 in Periapical Lesions with Apical Periodontitis and Microbial Analysis Outside the Apical Segment of Teeth

Publication date: Available online 6 February 2017
Source:Archives of Oral Biology
Author(s): Shujun Ran, Bin Liu, Shensheng Gu, Zhe Sun, Jingping Liang
ObjectiveTo detect the distribution and expression levels of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and the absent in Melanoma 2 (AIM2) inflammasomes in periapical lesions and to analyse the possible microbial stimuli outside of teeth.DesignThe distribution of NLRP3 and AIM2 inflammasomes in sixteen periapical lesions was investigated by immunohistochemistry. Meanwhile, the relative gene expression levels of NLRP3 and AIM2 in sixteen periapical lesions and three health periodontal tissue were quantified by real-time polymerase chain reaction (PCR). Moreover, forty-seven teeth without sinus tracts were obtained in the clinic and included in bacterial analysis using PCR. Then, the mRNA levels of apoptosis-associated speck-like protein (ASC), caspase-1, interleukin-1β (IL-1β), NLRP3 and AIM2 in THP-1-derived macrophages treated with lipopolysaccharides (LPS) of Porphyromonas were also quantified by real-time PCR, and the IL-1β secretion level was investigated using enzyme-linked immunosorbent assay (ELISA).ResultsNLRP3 and AIM2 were positively expressed in periapical lesions and were mainly distributed in inflammatory cells. Most of the samples that demonstrated up-regulation of NLRP3 mRNA also demonstrated up-regulation of caspase-1 mRNA. Microbial analysis revealed that Porphyromonas endodontalis was the most commonly detected species and was detected in 27 of 47 cases (57.4%), followed by Fusobacterium nucleatum (20/47, 42.6%), Porphyromonas gingivalis (19/47, 40.4%), Tannerella forsythia (19/47, 40.4%), Actinomyces sp (17/47, 36.17%), Treponema denticola (10/47,21.28%), Actinomyces israelii (9/47,19.15%), Prevotella intermedia (6/47, 12.77%), Enterococcus faecalis (1/47,2.13%) and Enterococcus faecium (0/47,0). Furthermore, we found that LPS of P. gingivalis induced THP-1 cells to produce IL-1β and to activate NLRP3 and AIM2 inflammasomes.ConclusionsOur results suggest that the NLRP3 and AIM2 proteins play a part in the pathogenesis of periapical periodontitis. Anaerobes, such as P. endodontalis, P. gingivalis, F. nucleatum and T. forsythia, were the main detected microbial stimuli that activate inflammasomes in periapical tissues.



http://ift.tt/2jWmOUa

Increased melatonin in oral mucosal tissue of oral lichen planus (OLP) patients: A possible link between melatonin and its role in oral mucosal inflammation

alertIcon.gif

Publication date: Available online 6 February 2017
Source:Archives of Oral Biology
Author(s): Kirawut Luengtrakoon, Worraned Wannakasemsuk, Vilasinee Vichitrananda, Poramaporn Klanrit, Doosadee Hormdee, Rajda Noisombut, Ponlatham Chaiyarit
ObjectiveThe existence of extra-pineal melatonin has been observed in various tissues. No prior studies of melatonin in human oral mucosal tissue under the condition of chronic inflammation have been reported. The aim of this study was to investigate the presence of melatonin in oral mucosal tissue of patients with oral lichen planus (OLP) which was considered as a chronic inflammatory immune-mediated disease causing oral mucosal damage and ulcerations.Materials and methodsSections from formalin-fixed and paraffin-embedded oral mucosal tissue of OLP patients (n=30), and control subjects (n=30) were used in this study. Immunohistochemical staining was performed and the semiquantitative scoring system was used to assess the levels of arylalkylamine-N-acetyltransferase (AANAT: a rate-limiting enzyme in the biosynthesis pathway of melatonin), melatonin, and melatonin receptor 1 (MT1) in oral mucosa of OLP patients and normal oral mucosa of control subjects.ResultsAANAT, melatonin, and MT1were detected in oral mucosal tissue of OLP patients and control subjects. Immunostaining scores of AANAT, melatonin, and MT1 in oral mucosal tissue of OLP patients were significantly higher than those in control subjects (p=0.002, p < 0.001, and p=0.031, respectively).ConclusionsIncreased levels of AANAT, melatonin, and MT1 in the inflamed oral mucosal tissue of OLP patients imply that chronic inflammation may induce the local biosynthesis of melatonin via AANAT, and may enhance the action of melatonin via MT1.



http://ift.tt/2kg5nKe

The role of hydroxychloroquine in the treatment of lichen planopilaris: A retrospective case series and review

Abstract

A variety of systemic agents are used to treat lichen planopilaris (LPP) with a limited evidence base. The aim of our study was to retrospectively review the response rate to and tolerability of hydroxychloroquine in a cohort of patients with LPP in an effort to add to the evidence base for its use. Twenty-three patients with a clinical and histopathological diagnosis of LPP who had been treated with hydroxychloroquine for their disease in a single center were identified. A retrospective review of these patients' medical records was performed and physician rated response was documented. Complete response was observed in 61% of our patients, and a further 9% of patients demonstrated partial response. Thirteen percent of patients withdrew from treatment because of suspected adverse effects. Our sample size was small, and data was collected retrospectively. We found hydroxychloroquine to be a reasonable therapeutic choice in LPP.



http://ift.tt/2kfVOLi

Pregabalin treatment of three cases with brachioradial pruritus

Abstract

Brachioradial pruritus (BRP) is a rare type of chronic pruritus that usually localized at the dorsolateral part of the forearms. Itching, burning, or pain are common symptoms at the involved areas. The etiological factors are still unknown but sun exposure and/or cervical spine lesions seem to be trigerring or precipiting factors. Neuropathogenic mechanism plays role in etiopathogenesis of BRP, therefore, antiepileptic drugs such as gabapentin, oxcarbazepine. and pregabalin are suggested medications for BRP. Herein, we report three cases with BRP successfully treated with pregabaline.



http://ift.tt/2jWzfj1

Unilesional plantar mycosis fungoides treated with topical photodynamic therapy - case report and review of the literature

Abstract

Background

Unilesional mycosis fungoides (UMF) and pagetoid reticulosis (PR) are variants of mycosis fungoides. Conventional therapy comprises surgical excision or radiotherapy which may be associated with long-term side effects, especially when the lesion is located at a special site like the palms and soles. Therefore, alternative treatment options are needed to treat solitary lesions in the case of UMF or PR. Recently topical photodynamic therapy (PDT) has been described to be an efficient and non-invasive therapeutical option with excellent clinical outcome.

Objective

The objective of this paper is to report a 43-year old woman with plantar UMF treated successfully with PDT, and to compare our findings with the data on PDT in UMF and PR reported in the literature.

Methods

The literature was analyzed for articles on UMF and PR, respectively, treated with topical PDT. Various parameters including form of PDT and response to treatment were analyzed and compared with our case.

Results

A total of 24 patients were documented with 24 lesions treated with PDT, either using aminolevulinic acid (ALA) or methylaminolevulinate (MAL). In average a single lesion was treated 19 times with PDT. In 21 cases (88%) complete response could be achieved, whereas 3 cases (13%) showed partial remission. None of the cases showed a stable or progression of the disease.

Conclusions

PDT is a safe, efficient and non-invasive therapeutical approach for the treatment of UMF and PR. It has no longstanding adverse events and therefore is of high therapeutic value especially in cases of UMF and PR located at special sites like the palms and soles. We propose to include topical PDT as therapeutic options for the treatment of UMF and PR in future guidelines on MF.

This article is protected by copyright. All rights reserved.



http://ift.tt/2kBxwN8

A case of linear basal cell carcinoma: evaluation of proliferative activity by immunohistochemical staining of PCTAIRE1 and p27

Abstract

Linear basal cell carcinoma (LBCC) is a unique morphological variant of basal cell carcinoma (BCC)1-3, and the mechanism behind the linear form has yet to be fully elucidated. To date, we have investigated the functions of p27 (Kip1) and PCTAIRE1 (also known as PCTK1, Cdk16) in tumorigenesis.4, 5 PCTAIRE1 is a member of the PCTAIRE family, which is related to the Cdk family, and it phosphorylates p27, leading to ubiquitination/degradation of this tumor suppressor.6, 7 An inverse correlation between p27 and PCTAIRE1 expressions has been observed in malignant tumors.

This article is protected by copyright. All rights reserved.



http://ift.tt/2kllb16

Small infantile hemangioma and breast hypoplasia

Abstract

Large and/or segmental infantile hemangiomas (IH) are sometimes associated with other localized and/or more widespread malformations such as those occurring in the PHACES (1). Breast hypoplasia occurring after IH has been barely reported (2). We report the case of a small IH of the breast, associated with a homolateral breast hypoplasia and we raise the question of a potential link between the 2 findings.

This article is protected by copyright. All rights reserved.



http://ift.tt/2kBFFBb

New-onset inflammatory bowel disease in adults with atopic dermatitis

Abstract

Atopic dermatitis (AD) is a common chronic and remitting inflammatory skin disease that affects children and adults. While some studies have reported an increased risk of Crohn's disease (CD), but not ulcerative colitis (UC), others have associated both conditions with AD. Notably, most studies have focused on IBD in childhood and adolescence.

This article is protected by copyright. All rights reserved.



http://ift.tt/2klonJK

Treatment history of patients receiving biologic therapy for psoriasis - a Danish nationwide study

Abstract

Psoriasis is a common skin disease affecting approximately 2-4% of the world's population.[1] Management of psoriasis often involves prolonged treatment with topical-, systemic-, and biologic agents. Topical agents, i.e. topical corticosteroids or topical vitamin D analogues, are considered first-line of treatment for psoriasis, whereas biologics are predominantly used as a last resort, often as the result of treatment failure of conventional systemic agents. However, the specific treatment algorithms may differ between patients and countries, and certain therapies may be used off-label.

This article is protected by copyright. All rights reserved.



http://ift.tt/2kBDwFv

Assessment of a 3-Dimensional Computerised PASI Tool for calculating and documenting psoriasis area and severity index scores

Abstract

Psoriasis Area and Severity Index(PASI) scoring was initially developed by Fredriksson and Pettersson in 1978[1], as a method to clinically evaluate and quantitate the amount and severity of psoriasis, and therefore the responses to a new treatment. Despite its advantages, there are numerous limitations such as high intra- and inter-observer variability and reproducibility in assessment of each of the PASI parameters[2], with scores varying two or three fold between scorers[2-5].

This article is protected by copyright. All rights reserved.



http://ift.tt/2klvhPr

The effect of mobile phone usage on hearing in adult population

Punnoose Philip, Satheesh Kumar Bhandary, Rajeswary Aroor, Vadish Bhat, Deepika Pratap

Indian Journal of Otology 2017 23(1):1-6

Background and Objective: The widespread use of mobile phones in recent years, especially among young people, has given rise to concerns about the potential influences of its electromagnetic fields (EMFs) on human health. The present study is conducted to investigate the adverse effects of mobile phone usage on auditory functions and to study the pattern of hearing threshold in mobile phone users. Materials and Methods: The study group consisted of 150 healthy volunteers between the age group of 21 and 45 years. They were divided into three groups; Group A consists of fifty participants who were using mobile phones for more than 1 h per day, Group B consists of fifty participants who were using mobile phones for <1 h per day, (both groups for a minimum period of 4 years), and Group C consists of fifty participants who did not use mobile phones or very occasional users (<1 h per week), being taken as control group. All participants underwent tympanometry and distortion product otoacoustic emission (DPOAE) tests and the results were compared among groups. Results: It is found that the prevalence of sensorineural hearing loss was seen in 10% participants of Group A and only 2% participants of Group B, but none among Group C had hearing loss, but this was statistically insignificant. The changes in DPOAEs were studied among groups and found significant difference between Group A (>1 h/day) and Group C (control group). Conclusion: The present study revealed that prolonged and frequent exposure to EMFs from mobile phone use can cause damage to the outer hair cells, especially in the basal turn of the cochlea, which can be detected by otoacoustic emission test and can subsequently lead to high frequency hearing loss.

http://ift.tt/2kH5tOz

Not a chondroma, but a cartilaginous choristoma of the bony external auditory canal

Jeong Hwan Choi

Indian Journal of Otology 2017 23(1):49-51

When the small white mass is found at the anterior wall of the bony external auditory canal (EAC) just in front of the short process of the malleus, the differential diagnosis of cartilaginous choristoma (CC) besides exostosis, osteoma, and keratoma should be included. CC of bony EAC is not as rare as it has been thought to be. Furthermore, it is very surprising that the term chondroma has been wrongly used to describe CC in many previous studies. In this report, I present my clinical experience with four patients with CC in the bony EAC and discuss the clinical importance of CC in differential diagnosis.

http://ift.tt/2jWkYxB

Disability certificate for individuals with hearing impairment – Time to rethink

Hemanth Narayan Shetty, Jijo Pottackal Mathai, Ajith Kumar Uppunda

Indian Journal of Otology 2017 23(1):7-12

Background: A retrospective research design was used to investigate the effect of degree of hearing loss on speech identification scores (SISs) and aided improvement in individuals with sensorineural hearing loss (SNHL) and auditory neuropathy spectrum disorder (ANSD). The present criteria (PWD Act, 2001) to issue disability certificate is suitable for individuals with SNHL, as there is a good agreement between their degree of hearing loss and speech understanding. In contrast, individuals with ANSD show severe speech understanding problems irrespective of their degree of hearing loss. Despite their problem, there are denied in giving disability certificate. The study also analyzed number of clients who have received the certificate of hearing disability, in both groups. Subjects and Methods: Clinical records of 165 clients who visited the Department of Audiology, All India Institute of Speech and Hearing, Mysore, India between October 2011 and October 2013 were reviewed. Results: Revealed that unlike SNHL, those with ANSD had no relation between the degree of hearing loss and SIS. In addition, aided improvement in ANSD was very limited and was not related to degree of hearing loss. All the individuals with SNHL, who had hearing loss above moderately severe degree received disability certificate. However, only 2 of the 36 clients with ANSD received disability certificate, although their hearing thresholds were above moderately severe degree. Conclusion: Pure-tone thresholds are not a deciding factor of speech understanding in ANSD. Thus, issue of disability certificate for ANSD should be based on SIS rather than pure-tone thresholds.

http://ift.tt/2kGX5Pg

Congenital absence of stapedius muscle and tendon: Rare finding in two cases

Deepak Dalmia, Sanjaya Kumar Behera

Indian Journal of Otology 2017 23(1):43-45

During surgery for otosclerosis, the surgeon cut the stapedius tendon before removing stapes suprastructure. The absence of the stapedius tendon is uncommon. In this case report, we present two cases of the absence of the unilateral stapedius tendon with muscle. During exploratory tympanotomy of the right ear in the first patient and left ear in the second patient with moderately severe mixed hearing loss, the absence of the stapedius tendon was found. The tympanic cavity was explored with the help of a Zeiss microscope by endomeatal route. The pyramidal process and stapedius muscle with its tendon were absent. Awareness of the variations or anomalies of the stapedius muscle and tendon is important for surgeons who operate upon the tympanic cavity, especially during surgery for ossicular fixation or ossicular discontinuity. As most of the time, these anomalies may be associated with the other middle ear anomalies.

http://ift.tt/2jWeWxh

Meniere's disease: A mystery! Our way to diagnose

Haris Manzoor Qadri, Arun Dehadaray, Maitri Kaushik, Danish Zamir Andrabi

Indian Journal of Otology 2017 23(1):13-16

Introduction: Meniere's disease (MD) has long posed a diagnostic challenge. Characterized by recurrent vertigo, tinnitus, and fluctuant sensorineural hearing loss (SNHL), its presentation may limit initially to merely one or two of the above symptoms. Inability to obtain a fresh inner ear tissue leaves us to rely on hypothetical choices. Materials and Methods: Two adjuvants, glycerol test, and intratympanic gentamycin, were analyzed in our study, for their efficacy in diagnosing MD. Patients with symptoms of vertigo, tinnitus, and SNHL were evaluated. Those with presbycusis, conductive hearing loss (on pure tone audiogram [PTA]), benign paroxysmal positional vertigo (diagnosed by Dix Hallpike), retrocochlear pathology (short increment sensitivity index score below 70%), and central cause (magnetic resonance imaging angiography and neurology opinion) were excluded. Rest were subjected to glycerol test and subsequently intratympanic gentamicin. After a 6 month follow up, evaluation was performed for tinnitus and vertigo through a visual analog scale. Repeat PTA was done to look for any hearing deterioration due to gentamicin. Results: It was found that not only did glycerol positive patients get completely relieved of vertigo but also those who tested negative got completely or partially relieved of it. This shows a higher efficacy of intratympanic gentamycin as well as its significant association with glycerol test. Conclusion: This study lead us to form a strong diagnostic criterion which has already proven to be therapeutic in the management of MD.

http://ift.tt/2kGUswI

Kyasanur forest disease

Pranathi Kavi, PG Bhargavi

Indian Journal of Otology 2017 23(1):56-58

Kyasanur forest disease (KFD) a rare viral disease found to be related to the Russian-spring summer virus but differs only because of its hemorrhagic form. KFD is known to be prevalent in the Shimoga District of Karnataka, and it was first identified in the year 1957. Victims of this disease would be those who have been exposed to deceased monkeys in forests or otherwise, have been bitten by an infected tick. Some of the initial phase symptoms include persistent headaches, fever, and muscle weakness. However, the neurological symptoms begin to appear only in the second phase of the viral attack. At this stage, viral encephalopathy, meningoencephalitis, or even meningitis could manifest and lead to vast deficits. Previous literature reviews of this disease have shown no signs of language deficits. A case of a 5-year-old child, confirmed with the KFD, with diffuse encephalopathy as well as other organ functioning deficits, showed deficits in language skills.

http://ift.tt/2jWgTcJ

Silver cauterization: An office procedure for repair of small tympanic membrane perforation

Mohammad Waheed El-Anwar, Mohammad El-Sayed Abd Elbary, Ibrahim Mohammad Saber

Indian Journal of Otology 2017 23(1):17-20

Introduction: Patients with small tympanic membrane (TM) perforations often suffer from repeated infections rather than hearing loss. Repair of TM perforations is required regardless of its size, as without closure, morbidity may include hearing loss, chronic otorrhea, and cholesteatoma formation. Objective: To assess the effectiveness of the topical silver cauterization to refresh and close small TM perforation as an office-based procedure. Materials and Methods: Thirteen patients with small TM perforations were enrolled in the study. The margin of the perforation was cauterized using silver nitrate 10% that was repeated up to six times. The procedure was considered successful if there was no residual perforation within the follow-up period. Postoperative audiometry was performed before cauterization then at 3 months after. Results: Successful perforation repair was achieved in ten ears (76.9%). Mean hearing gain was 11.5 ± 8 for all cases and 15 ± 5.27 for succeeded cases. None of the patients developed infection, hearing impairment, tinnitus, vertigo, bleeding, taste disturbance, or hyperkeratosis. Conclusion: Office-based silver cautery is a safe, effective, and minimally invasive procedure. It is suitable for repairing small TM perforations with comparable success rate to conventional myringoplasty.

http://ift.tt/2jWkYh5

To study the results of àWengen titanium clip piston prosthesis in stapedotomy

Raman Wadhera, Madhuri Kaintura, Sharad Hernot, Sandeep Bhukar, S Dheeraj, Usha Sehrawat, Jitu Sam George

Indian Journal of Otology 2017 23(1):36-42

Objective: To study the hearing results in patients implanted with àWengen titanium clip piston prosthesis after stapedotomy. Methods: In this prospective study, 15 patients of either sex in the age group of 18–50 years having conductive hearing loss with an air-bone gap (ABG) of 30 dB or more, with an intact tympanic membrane, and A or As type of curve in tympanometry were recruited. All patients underwent stapedotomy using àWengen titanium clip piston (Kurz, Germany) which was designed to avoid the scrupulous task of crimping a piston onto the long process of incus. The results were tabulated in accordance with the guidelines set by the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery (1994) at frequencies of 0.5, 1, 2 and 3 kHz. The follow-up period was 3 months. Results: The mean preoperative bone conduction (BC) was 16.00 ± 6.02 dB, at 6 weeks postoperative was 16.58 ± 12.40 dB, and at 3 months was 16.00 ± 10.80 dB. The mean preoperative ABG was 42 ± 7.26 dB, at 6 weeks postoperative was 20.5 ± 9.77 dB, and at 3 months was 17.25 ± 10.59 dB. There was improvement in postoperative BC, as well as ABG in 14 patients (except one). Conclusion: The use of the àWengen titanium clip stapes piston gives good results in cases of stapedotomy for otosclerosis. It is easy to insert onto the long process of incus and evades the complex step of crimping. The gain in hearing post surgery is comparable with the other types of pistons reported in literature.

http://ift.tt/2kGVY27

Influence of channel and ChannelFree™ processing technology on the vocal parameters in hearing-impaired individuals

Gopika Kizhakke Kodiyath, Kishan Madikeri Mohan, Rajashekhar Bellur

Indian Journal of Otology 2017 23(1):21-26

Introduction: Hearing loss is common in all age ranged population. Hearing loss leads to poor speech perception in quiet and more in noisy situation. Intact system over comes problem by masking release ability and its mechanism however impaired system fails to do. Hearing aid being common rehabilitation option, strategies and technology tries to support better speech perception in noise. Hence comparative studies of technology and strategies for the betterment of impaired population are needed. Objective of the Study: Enhancing speech perception is being the mainstay of hearing aid manufactures, Comparison of ChannelFreeTM, novel technology which claiming superior speech perception with channel hearing aids, specifically for competing signals is the objective. Materials and Methods: Thirty-three clients fitted with multi-channel and ChannelFreeTM with noise reductions (NR) On, Off condition. Comodulated and Uncomodulated masking release was the outcome measure in free field condition through audiometer. Results: Overall, ChannelFreeTM performed superior over channel hearing aids. Effect of channels, NR, and modulation type of background noise played key role. Perceptually, ChannelFreeTM was significantly preferred, especially in the first time users. Conclusion: ChannelFreeTM hearing aid strategies and NR are able to process incoming signal faster in order to retain the spectral contrast and also facilitate temporal cues from the amplified speech in noise. Acclimatization period has a vital role. Updating and implementing the validated novel technologies for the hearing impaired individual is recommended.

http://ift.tt/2jWeUp9

Prelingual auditory verbal agnosia, A rare condition

Violeta Necula, Cristina Mirela Stamate, Krishna Luchoo, Marcel Cosgarea

Indian Journal of Otology 2017 23(1):46-48

Auditory agnosia, agnosia for speech is a rare condition, caused mostly by stroke, in adults, while in children it is often a sequel of herpes simplex encephalitis or is associated with epilepsy, in Landau–Kleffner syndrome. This article presents a rare case of verbal auditory agnosia as a result of meningoencephalitis, caused probably by herpes simplex virus. The patient's developed encephalitis at the age of 1 year and 4 months. After her recovery, the family noticed the absence of language development. She was initially diagnosed with profound hearing loss, and the hearing aids did not help her. The speech therapy developed her lip-reading skills with a hard-to-understand pronunciation. Later, audiometry showed a nearly normal peripheral auditory system and magnetic resonance imaging revealed the characteristic brain lesions in both the temporal lobes, explaining the patient's evolution. Assessment of children with delayed speech development must consider the central hearing disorders as a differential diagnosis.

http://ift.tt/2kH0EVH

Sound localization performance in children with cochlear implants using bimodal stimulation

Poonam Raj, Sachin Saini, AK Mishra

Indian Journal of Otology 2017 23(1):27-31

Introduction: There are clear benefits of having bilateral inputs to the auditory nervous system. Hearing-impaired children are, therefore, generally fitted with two hearing aids so that they can benefit from hearing binaurally. Children who use a cochlear implant in one ear and no amplification in the opposite ear are, however, deprived of these advantages. The current study was undertaken to determine the benefits of bimodal stimulation in pediatric population. Methods and Materials: This study comprised of 20 children between 6-11 years of age with profound bilateral sensorineural hearing loss with cochlear implant in one ear and fitted with digital hearing aid in non-implanted ear. Mean sound localization score was compared in children with cochlear implant only and those with both cochlear implant and hearing aid. Result: A statistically significant difference was found between mean sound localization in both test condition under quiet surrounding. Conclusion: Hence it is suggested that the use of bimodal fitting can be considered as an effective management option in order to obtain binaural hearing benefits in children who undergo unilateral cochlear implantation.

http://ift.tt/2jVUaxI

Organized hematoma of the maxillary sinus mimicking tumor

Jeong Hwan Choi

Indian Journal of Otology 2017 23(1):52-55

Sinonasal organized hematomas are rare, nonneoplastic, benign lesions that usually arise in the maxillary sinus. They are composed of neovascularization in a hematoma and surrounding organizing fibrotic tissue. Factors that may predispose a patient to hematoma formation are vary, and the pathogenesis of the mass is still uncertain. They have the potential for progressive bony erosion and compression of adjacent structures. They are a diagnostic dilemma clinically and radiologically mimicking benign diseases such as inverted papilloma or even malignant neoplasms and causing clinicians undue worry regarding these diagnoses.

http://ift.tt/2kGUUez

Interlay Type I tympanoplasty in large central perforations: Analysis of 500 cases

Satish Jain, Nitika Gupta, Rohan Gupta, Abhinav Roy

Indian Journal of Otology 2017 23(1):32-35

Aims and Objectives: To study the outcomes of interlay tympanoplasty (Type I) in patients with large central perforations (inactive mucosal chronic otitis media [COM]) in terms of graft uptake and hearing improvement. Materials and Methods: The present study is an analysis of database of 500 patients of inactive mucosal COM with large central perforation, who had undergone Type I interlay tympanoplasty at Jain ENT Hospital, Jaipur, during the past 5 years. Results: The graft uptake rate in the present study was found to be 96.6%, and 95.4% of the patients reported an improvement in terms of hearing with the mean air-bone gap improving from 26.08 to 10.12 dB. Conclusion: Tympanoplasty done by interlay technique has excellent results both in terms of graft uptake and hearing improvement, with minimal complications.

http://ift.tt/2jW51Ym

First branchial cleft anomaly presenting as recurrent postauricular cyst

Prakriti Shukla, Uroos Fatima

Indian Journal of Otology 2017 23(1):59-61

First branchial cleft anomalies are a special group of congenital malformations that represent <10% of all branchial cleft anomalies. They may present as cysts, swellings, or fistulas in the periauricular region or in the lateral aspect of the neck. Failure to identify these lesions can lead to delay in the diagnosis, often misdiagnosis, inadequate treatment, and subsequent recurrence. We report a case of 15-year-old girl who presented with recurrent postauricular cyst. Fine-needle aspiration biopsy was performed, and it was diagnosed as infected cystic lesion. On histopathological examination, the diagnosis was confirmed as first branchial cleft cyst.

http://ift.tt/2kGUTav

A Report of Two Cases of Solid Facial Edema in Acne

Abstract

Introduction

Solid facial edema (SFE) is a rare complication of acne vulgaris. To examine the clinical features of acne patients with solid facial edema, and to give an overview on the outcome of previous topical and systemic treatments in the cases so far published.

Methods

We report two cases from Switzerland, both young men with initially papulopustular acne resistant to topical retinoids.

Results

Both cases responded to oral isotretinoin, in one case combined with oral steroids. Our cases show a strikingly similar clinical appearance to the cases described by Connelly and Winkelmann in 1985 (Connelly MG, Winkelmann RK. Solid facial edema as a complication of acne vulgaris. Arch Dermatol. 1985;121(1):87), as well as to cases of Morbihan's disease that occurs as a rare complication of rosacea.

Conclusion

Even 30 years after, the cause of the edema remains unknown. In two of the original four cases, a potential triggering factor was identified such as facial trauma or insect bites; however, our two patients did not report such occurrencies. The rare cases of solid facial edema in both acne and rosacea might hold the key to understanding the specific inflammatory pattern that creates both persisting inflammation and disturbed fluid homeostasis which can occur as a slightly different presentation in dermatomyositis, angioedema, Heerfordt's syndrome and other conditions.



http://ift.tt/2liVVqL

Lipoma of Columella with septal extension in Pai syndrome: report of a rare case

Abstract

Background

Lipoma in nasal region in a case of Pai syndrome is very rare. Very few cases of Pai syndrome with columellar lipoma with extension to septum and tip have been reported till date.

Case presentation

We report a very rare form of nasal lipoma in a case of Pai syndrome with extension to septum and tip in a 4 year old female child.

Conclusions

Pai syndrome with columellar lipoma with septal and tip extension should always be kept in mind when evaluating a swelling in the region of nasal tip, collumella and septum with notch in upper lip and corpus callosal lipoma.



http://ift.tt/2kGZo4Z

Outcomes of Using Otoendoscopy During Surgery for Cholesteatoma

Abstract

To determine the impact of using otoendoscopy at the time of primary surgery of cholesteatoma in identifying hidden "cholesteatoma remnant". Study was prospective study. Setting was University tertiary care hospital. One hundred fifty, patients diagnosed clinically and by CT as having cholesteatoma, have been operated. 64 patients operated by using canal up technique and 86 patients operated by using canal down technique. Once all visible cholesteatoma was removed with standard microscopic techniques, otoendoscopy was utilized in every patient to identify any hidden "cholesteatoma remnant". Despite apparent total microscopic eradication of cholesteatoma of the operated cases, otoendoscopy at time of primary surgery revealed an overall incidence of hidden cholesteatoma remnants of 18%. The incidence of hidden cholesteatoma remnants identified by otoendoscopy was 23% in the canal up group and 14% in the canal down group. Otoendoscopy should be used as an adjunct with standard microscopic technique to identify hidden cholesteatoma remnants during surgery of cholesteatoma.



http://ift.tt/2kFhC6x

Use of autogenous bone and beta-tricalcium phosphate in maxillary sinus lifting: histomorphometric study and immunohistochemical assessment of RUNX2 and VEGF

The aim of this study was to compare the use of beta-tricalcium phosphate (β-TCP) (chronOS) with autogenous bone grafts alone in maxillary sinus elevation surgery. The test samples were β-TCP alone, β-TCP mixed with autogenous bone grafts (1:1), and autogenous bone grafts alone. Twelve maxillary sinuses were grafted with β-TCP (group 1), nine with β-TCP+autogenous bone graft (group 2), and 12 with autogenous bone graft (group 3). After 6 months, biopsies were obtained concurrent to the placement of dental implants; these were subjected to histomorphometric analysis and immunohistochemical analysis for runt-related transcription factor 2 (RUNX2) and vascular endothelial growth factor (VEGF).

http://ift.tt/2kMftG0

Validation of selective use of intraoperative PTH monitoring in parathyroidectomy

The objective of this study was to validate our approach of treating primary hyperparathyroidism using sestamibi scan directed parathyroidectomy, without routine use of intraoperative parathyroid hormone measu...

http://ift.tt/2kM7l8v

Human Blood CD1c+ Dendritic Cells Encompass CD5high and CD5low Subsets That Differ Significantly in Phenotype, Gene Expression, and Functions [IMMUNE SYSTEM DEVELOPMENT]

There are three major dendritic cell (DC) subsets in both humans and mice, that is, plasmacytoid DCs and two types of conventional DCs (cDCs), cDC1s and cDC2s. cDC2s are important for polarizing CD4+ naive T cells into different subsets, including Th1, Th2, Th17, Th22, and regulatory T cells. In mice, cDC2s can be further divided into phenotypically and functionally distinct subgroups. However, subsets of human cDC2s have not been reported. In the present study, we showed that human blood CD1c+ cDCs (cDC2s) can be further separated into two subpopulations according to their CD5 expression status. Comparative transcriptome analyses showed that the CD5high DCs expressed higher levels of cDC2-specific genes, including IFN regulatory factor 4, which is essential for the cDC2 development and its migration to lymph nodes. In contrast, CD5low DCs preferentially expressed monocyte-related genes, including the lineage-specific transcription factor MAFB. Furthermore, compared with the CD5low subpopulation, the CD5high subpopulation showed stronger migration toward CCL21 and overrepresentation among migratory DCs in lymph nodes. Additionally, the CD5high DCs induced naive T cell proliferation more potently than did the CD5low DCs. Moreover, CD5high DCs induced higher levels of IL-10–, IL-22–, and IL-4–producing T cell formation, whereas CD5low DCs induced higher levels of IFN-–producing T cell formation. Thus, we show that human blood CD1c+ cDC2s encompass two subsets that differ significantly in phenotype, that is, gene expression and functions. We propose that these two subsets of human cDC2s could potentially play contrasting roles in immunity or tolerance.



http://ift.tt/2lhlYxv

Osteosynthesis using cannulated headless Herbert screws in mandibular angle fracture treatment: A new approach?

Fractures of the mandibular angle are a common type of facial skull fracture. Although operative treatment includes a wide range of fixation techniques, a definite gold standard method has yet to be established. Headless, cannulated Herbert screws, often used in many forms of minimally invasive trauma surgery, provide functional and stable fracture fixation.

http://ift.tt/2ldd34j

Neoclassical canons of facial beauty: do we see the deviations?

To explore the presence of neoclassical canons of facial beauty among young people in Croatia and to question possible psychosocial repercussions occurring in those who demonstrate deviations in relation to canons.

http://ift.tt/2liiawX

Long-term follow-up study of patients with a unilateral complete cleft of lip, alveolus, and palate following the Utrecht treatment protocol: dental arch relationships

This study sought to evaluate long-term dental arch relationships in adults with a unilateral complete cleft lip and palate (UCLP) treated by the Utrecht protocol and to compare results with the centers from the Eurocleft study.

http://ift.tt/2jVXY6P

Periosteal distraction osteogenesis versus immediate periosteal elevation in a rat model: histological and micro-CT analysis

The aim of the present study was to compare periosteal distraction osteogenesis (PDO) to immediate periosteal elevation (IPE) in terms of de novo bone formation.

http://ift.tt/2kfnhwJ

Lipoma of Columella with septal extension in Pai syndrome: report of a rare case

Lipoma in nasal region in a case of Pai syndrome is very rare. Very few cases of Pai syndrome with columellar lipoma with extension to septum and tip have been reported till date.

http://ift.tt/2jVICiW

A B Cell Epitope Peptide Derived from the Major Grass Pollen Allergen Phl p 1 Boosts Allergen-Specific Secondary Antibody Responses without Allergen-Specific T Cell Help [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

More than 40% of allergic patients suffer from grass pollen allergy. Phl p 1, the major timothy grass pollen allergen, belongs to the cross-reactive group 1 grass pollen allergens that are thought to initiate allergic sensitization to grass pollen. Repeated allergen encounter boosts allergen-specific IgE production and enhances clinical sensitivity in patients. To investigate immunological mechanisms underlying the boosting of allergen-specific secondary IgE Ab responses and the allergen epitopes involved, a murine model for Phl p 1 was established. A B cell epitope–derived peptide of Phl p 1 devoid of allergen-specific T cell epitopes, as recognized by BALB/c mice, was fused to an allergen-unrelated carrier in the form of a recombinant fusion protein and used for sensitization. This fusion protein allowed the induction of allergen-specific IgE Ab responses without allergen-specific T cell help. Allergen-specific Ab responses were subsequently boosted with molecules containing the B cell epitope–derived peptide without carrier or linked to other allergen-unrelated carriers. Oligomeric peptide bound to a carrier different from that which had been used for sensitization boosted allergen-specific secondary IgE responses without a detectable allergen-specific T cell response. Our results indicate that allergen-specific secondary IgE Ab responses can be boosted by repetitive B cell epitopes without allergen-specific T cell help by cross-linking of the B cell epitope receptor. This finding has important implications for the design of new allergy vaccines.



http://ift.tt/2lhl2JG

Natalizumab for Multiple Sclerosis: A Case in Point for the Impact of Translational Neuroimmunology [TRANSLATING IMMUNOLOGY]

Advances in translational neuroimmunology over the last two decades have revolutionized the treatment of relapsing forms of multiple sclerosis. A pathological hallmark of multiple sclerosis is the presence of leukocytes in the areas of disease activity in the CNS. Natalizumab inhibits the trafficking of lymphocytes from the blood into the brain and spinal cord by blocking the adhesion molecule α4-integrin. Representing the enormous success of a molecular targeted approach, natalizumab was the first mAb approved for the treatment of relapsing–remitting multiple sclerosis. However, only a few months after its approval, natalizumab was withdrawn from the market because of an unanticipated life threatening adverse effect: progressive multifocal leukoencephalopathy. Natalizumab was later reintroduced with required adherence to a strict monitoring program. In this article, we review the bench-to-bedside journey of natalizumab, along with the lessons learned from postmarketing studies.



http://ift.tt/2lh581Y

A New RNA-Based Adjuvant Enhances Virus-Specific Vaccine Responses by Locally Triggering TLR- and RLH-Dependent Effects [IMMUNOTHERAPY AND VACCINES]

Among innovative adjuvants conferring a Th1-shift, RNAdjuvant is a promising candidate. This adjuvant consists of a 547-nt uncapped noncoding ssRNA containing polyU repeats that is stabilized by a cationic carrier peptide. Whereas vaccination of mice with an influenza subunit vaccine induced moderate virus-specific IgG1, vaccination together with RNAdjuvant significantly enhanced this IgG1 and additionally promoted the formation of IgG2b/c, which is indicative of Th1 responses. Furthermore, such sera neutralized influenza virus, whereas this effect was not detected upon vaccination with the subunit vaccine alone. Similarly, upon vaccination with virus-like particles displaying vesicular stomatitis virus G protein, RNAdjuvant promoted the formation of virus-specific IgG2b/c and enhanced neutralizing IgG responses to an extent that mice were protected against lethal virus infection. RNAdjuvant induced dendritic cells to upregulate activation markers and produce IFN-I. Although these effects were strictly TLR7 dependent, RNAdjuvant-mediated augmentation of vaccine responses needed concurrent TLR and RIG-I–like helicase signaling. This was indicated by the absence of the adjuvant effect in vaccinated MyD88–/–Cardif–/– mice, which are devoid of TLR (with the exception of TLR3) and RIG-I–like helicase signaling, whereas in vaccinated MyD88–/– mice the adjuvant effect was reduced. Notably, i.m. RNAdjuvant injection induced local IFN-I responses and did not induce systemic effects, implying good tolerability and a favorable safety profile for RNAdjuvant.



http://ift.tt/2lh451W

Efferocytosis Signaling in the Regulation of Macrophage Inflammatory Responses [BRIEF REVIEWS]

Since the pioneering work of Elie Metchnikoff and the discovery of cellular immunity, the phagocytic clearance of cellular debris has been considered an integral component of resolving inflammation and restoring function of damaged and infected tissues. We now know that the phagocytic clearance of dying cells (efferocytosis), particularly by macrophages and other immune phagocytes, has profound consequences on innate and adaptive immune responses in inflamed tissues. These immunomodulatory effects result from an array of molecular signaling events between macrophages, dying cells, and other tissue-resident cells. In recent years, many of these molecular pathways have been identified and studied in the context of tissue inflammation, helping us better understand the relationship between efferocytosis and inflammation. We review specific types of efferocytosis-related signals that can impact macrophage immune responses and discuss their relevance to inflammation-related diseases.



http://ift.tt/2lcVJw5

In This Issue [IN THIS ISSUE]



http://ift.tt/2lcROQ1

Alarmins: Feel the Stress [BRIEF REVIEWS]

Over the last decade, danger-associated molecular pattern molecules, or alarmins, have been recognized as signaling mediators of sterile inflammatory responses after trauma and injury. In contrast with the accepted passive release models suggested by the "danger hypothesis," it was recently shown that alarmins can also directly sense and report damage by signaling to the environment when released from live cells undergoing physiological stress, even without loss of subcellular compartmentalization. In this article, we review the involvement of alarmins such as IL-1α, IL-33, IL-16, and high-mobility group box 1 in cellular and physiological stress, and suggest a novel activity of these molecules as central initiators of sterile inflammation in response to nonlethal stress, a function we denote "stressorins." We highlight the role of posttranslational modifications of stressorins as key regulators of their activity and propose that targeted inhibition of stressorins or their modifiers could serve as attractive new anti-inflammatory treatments for a broad range of diseases.



http://ift.tt/2lhdcjf

The Role of the p38-MNK-eIF4E Signaling Axis in TNF Production Downstream of the NOD1 Receptor [INNATE IMMUNITY AND INFLAMMATION]

Activation of nucleotide-binding oligomerization domain (NOD) 1 and NOD2 by muropeptides triggers a complex transcriptional program in innate immune cells. However, little is known about posttranscriptional regulation of NOD1- and NOD2-dependent responses. When stimulated with a prototypic NOD1 agonist, N-acetylglucosaminyl–N-acetylmuramyl–l-alanyl-d-isoglutamyl-meso-diaminopimelic acid (GM-triDAP), human monocyte-derived macrophages (MDM) produced an order of magnitude more TNF, IL-6, and pro–IL-1β than did monocyte-derived dendritic cells (MDDC), despite similar NOD1 expression, similar cytokine mRNA kinetics, and comparable responses to LPS. TNF production by GM-triDAP–activated MDM was independent of autocrine IL-1. However, GM-triDAP–activated MDM translated TNF mRNA more efficiently than did MDDC. As an underlying mechanism, NOD1 triggering in MDM caused a more potent and long-lasting activation of the signaling axis involving p38 MAPK, MAPK-interacting kinase (MNK), and eukaryotic translation initiation factor 4E, which is a critical regulator of translation. Furthermore, MNK controlled TNF mRNA abundance in MDDC and MDM upon NOD1 triggering. NOD1-dependent responses were more sensitive to MNK inhibition than were TLR4-dependent responses. These results demonstrate the importance of the p38–MNK–eukaryotic translation initiation factor 4E axis in TNF production downstream of NOD1.



http://ift.tt/2lhl2ta

Contact, Collaboration, and Conflict: Signal Integration of Syk-Coupled C-Type Lectin Receptors [BRIEF REVIEWS]

Several spleen tyrosine kinase–coupled C-type lectin receptors (CLRs) have emerged as important pattern recognition receptors for infectious danger. Because encounter with microbial pathogens leads to the simultaneous ligation of several CLRs and TLRs, the signals emanating from different pattern recognition receptors have to be integrated to achieve appropriate biological responses. In this review, we briefly summarize current knowledge about ligand recognition and core signaling by Syk-coupled CLRs. We then address mechanisms of synergistic and antagonistic crosstalk between different CLRs and with TLRs. Emerging evidence suggests that signal integration occurs through 1) direct interaction between receptors, 2) regulation of expression levels and localization, and 3) collaborative or conflicting signaling interference. Accordingly, we aim to provide a conceptual framework for the complex and sometimes unexpected outcome of CLR ligation in bacterial and fungal infection.



http://ift.tt/2lcWeGF

CD8+ T Cells That Coexpress ROR{gamma}t and T-bet Are Functionally Impaired and Expand in Patients with Distal Bile Duct Cancer [TUMOR IMMUNOLOGY]

CD8+ T cells that express retinoic acid–related orphan receptor (ROR)t (TC17 cells) have been shown to promote procarcinogenic inflammation and contribute to a tolerogenic microenvironment in tumors. We investigated their phenotype and functional properties in relationship to the pathogenesis of human distal bile duct cancer (DBDC). DBDC patients had an elevated level of type 17 immune responses and the frequency of CD8+RORt+ T cells (TC17 cells) was increased in peripheral blood. The CD8+RORt+ T cells represented a highly activated subset and produced IL-17A in equal amount as CD4+RORt+ T cells (TH17 cells). Most CD8+RORt+ T cells coexpressed T-bet, a lineage transcription factor for TH1 and TC1 development, suggesting that CD8+RORt+ T cells undergo plasticity toward a TC17/1-like phenotype with coproduction of IL-17A and INF-. In comparison with CD8+RORt T cells, the CD8+RORt+ T cells had a higher level of TCR signaling and were terminally differentiated and exhausted. These cells also had impaired ability to re-express perforin after degranulation and reduced cytotoxic immune function. A subset of CD8+RORt+ T cells expressing a low level of programmed cell death protein 1 and a high level of OX40 were associated with reduced patient survival. In conclusion, CD8+RORt+ T cells are proinflammatory and functionally impaired and may contribute to the pathogenesis of DBDC.



http://ift.tt/2lh2Z6r

Cutting Edge: Human CD49e- NK Cells Are Tissue Resident in the Liver [CUTTING EDGE]

Most knowledge on NK cells is based on studies of what are now known as conventional NK cells in the mouse spleen or human peripheral blood. However, recent studies in mice indicate the presence of tissue-resident NK cells in certain organs, such as the liver, that display different markers and transcription factor dependencies as compared with conventional NK cells. In this study, we provide evidence from cytometry by time-of-flight analysis and humanized mice indicating that human CD49e NK cells are tissue resident in the liver. Thus, these studies indicate that tissue-resident NK cells are evolutionarily conserved in humans and mice, providing a foundation to explore their role in human disease.



http://ift.tt/2lhm0FD

Effective Combination of Innate and Adaptive Immunotherapeutic Approaches in a Mouse Melanoma Model [IMMUNOTHERAPY AND VACCINES]

Most cancer immunotherapies include activation of either innate or adaptive immune responses. We hypothesized that the combined activation of both innate and adaptive immunity will result in better antitumor efficacy. We have previously shown the synergy of an agonistic anti-CD40 mAb (anti-CD40) and CpG-oligodeoxynucleotides in activating macrophages to induce tumor cell killing in mice. Separately, we have shown that a direct intratumoral injection of immunocytokine (IC), an anti-GD2 Ab linked to IL-2, can activate T and NK cells resulting in antitumor effects. We hypothesized that activation of macrophages with anti-CD40/CpG, and NK cells with IC, would cause innate tumor destruction, leading to increased presentation of tumor Ags and adaptive T cell activation; the latter could be further augmented by anti–CTLA-4 Ab to achieve tumor eradication and immunological memory. Using the mouse GD2+ B78 melanoma model, we show that anti-CD40/CpG treatment led to upregulation of T cell activation markers in draining lymph nodes. Anti-CD40/CpG + IC/anti–CTLA-4 synergistically induced regression of advanced s.c. tumors, resulting in cure of some mice and development of immunological memory against B78 and wild type B16 tumors. Although the antitumor effect of anti-CD40/CpG did not require T cells, the antitumor effect of IC/anti–CTLA-4 was dependent on T cells. The combined treatment with anti-CD40/CpG + IC/anti-CTLA-4 reduced T regulatory cells in the tumors and was effective against distant solid tumors and lung metastases. We suggest that a combination of anti-CD40/CpG and IC/anti-CTLA-4 should be developed for clinical testing as a potentially effective novel immunotherapy strategy.



http://ift.tt/2lh8sdl

Cutting Edge: NANOG Activates Autophagy under Hypoxic Stress by Binding to BNIP3L Promoter [CUTTING EDGE]

Hypoxia upregulates the core pluripotency factors NANOG, SOX2, and OCT4, associated with tumor aggressiveness and resistance to conventional anticancer treatments. We have previously reported that hypoxia-induced NANOG contributed in vitro to tumor cell resistance to autologous-specific CTL and in vivo to the in situ recruitment of immune-suppressive cells. In this study, we investigated the mechanisms underlying NANOG-mediated tumor cell resistance to specific lysis under hypoxia. We demonstrated the tumor-promoting effect of hypoxia on tumor initiation into immunodeficient mice using human non–small lung carcinoma cells. We next showed a link between NANOG and autophagy activation under hypoxia because inhibition of NANOG decreased autophagy in tumor cells. Chromatin immunoprecipitation and luciferase reporter assays revealed a direct binding of NANOG to a transcriptionally active site in a BNIP3L enhancer sequence. These data establish a new link between the pluripotency factor NANOG and autophagy involved in resistance to CTL under hypoxia.



http://ift.tt/2lcU1e8

Widespread Virus Replication in Alveoli Drives Acute Respiratory Distress Syndrome in Aerosolized H5N1 Influenza Infection of Macaques [INFECTIOUS DISEASE AND HOST RESPONSE]

Human infections with highly pathogenic avian influenza A (H5N1) virus are frequently fatal but the mechanisms of disease remain ill-defined. H5N1 infection is associated with intense production of proinflammatory cytokines, but whether this cytokine storm is the main cause of fatality or is a consequence of extensive virus replication that itself drives disease remains controversial. Conventional intratracheal inoculation of a liquid suspension of H5N1 influenza virus in nonhuman primates likely results in efficient clearance of virus within the upper respiratory tract and rarely produces severe disease. We reasoned that small particle aerosols of virus would penetrate the lower respiratory tract and blanket alveoli where target cells reside. We show that inhalation of aerosolized H5N1 influenza virus in cynomolgus macaques results in fulminant pneumonia that rapidly progresses to acute respiratory distress syndrome with a fatal outcome reminiscent of human disease. Molecular imaging revealed intense lung inflammation coincident with massive increases in proinflammatory proteins and IFN-α in distal airways. Aerosolized H5N1 exposure decimated alveolar macrophages, which were widely infected and caused marked influx of interstitial macrophages and neutrophils. Extensive infection of alveolar epithelial cells caused apoptosis and leakage of albumin into airways, reflecting loss of epithelial barrier function. These data establish inhalation of aerosolized virus as a critical source of exposure for fatal human infection and reveal that direct viral effects in alveoli mediate H5N1 disease. This new nonhuman primate model will advance vaccine and therapeutic approaches to prevent and treat human disease caused by highly pathogenic avian influenza viruses.



http://ift.tt/2lheaM5

Functional Conversion and Dominance of {gamma}{delta} T Subset in Mouse Experimental Autoimmune Uveitis [AUTOIMMUNITY]

We have previously shown that activated T cells have a much stronger proinflammatory effect in the development of experimental autoimmune uveitis than their nonactivated counterparts. Our present study explored T cell subsets are functionally distinct in autoimmune pathogenesis and determined the pathogenic contribution of biased V4+ T cell activation in this disease. By systematically comparing two major peripheral T cell subsets, the V1+ and the V4+ cells, we found that the V4+ cells were readily activated in B6 mice during experimental autoimmune uveitis development, whereas V1+ cells remained nonactivated. Cytokines that were abundantly found in the serum of immunized mice activated V4+, but did not activate V1+, cells. The V4+ cells had a strong proinflammatory activity, whereas the V1+ cells remained nonactivated when tested immediately after isolation from immunized mice. However, when the V1+ cells were activated in vitro, they promoted inflammation. Our results demonstrated that activation is a major factor in switching the enhancing and inhibiting effects of both V1+ and V4+ T cell subsets, and that T cell subsets differ greatly in their activation requirements. Whether the enhancing or inhibiting function of T cells is dominant is mainly determined by the proportion of the T cells that are activated versus the proportion not activated.



http://ift.tt/2lhl3gI

Inactivation of Rab11a GTPase in Macrophages Facilitates Phagocytosis of Apoptotic Neutrophils [INNATE IMMUNITY AND INFLAMMATION]

The timely and efficient clearance of apoptotic neutrophils by macrophages (efferocytosis) is required for the resolution of inflammation and tissue repair, but the regulatory mechanisms remain unclear. In this study, we investigated the role of the small GTPase Ras-related protein in brain (Rab)11a in regulating efferocytosis, and on this basis the resolution of inflammatory lung injury. We observed that apoptotic neutrophil feeding induced a rapid loss of Rab11a activity in bone marrow–derived macrophages and found that depletion of Rab11a in macrophages by small interfering RNA dramatically increased the phagocytosis of apoptotic neutrophils compared with control cells. Additionally, overexpression of wild-type Rab11a inhibited macrophage efferocytosis, whereas overexpression of dominant-negative Rab11a (Rab11a S25N) increased the clearance of apoptotic neutrophils. Rab11a knockdown also increased the surface level of CD36 in macrophages, but it reduced cell surface expression of a disintegrin and metalloproteinase (ADAM) 17. Depletion of ADAM17 rescued the decreased surface CD36 expression found in macrophages overexpressing wild-type Rab11a. Also, blockade of CD36 abolished the augmented efferocytosis seen in Rab11a-depleted macrophages. In mice challenged with endotoxin, intratracheal instillation of Rab11a-depleted macrophages reduced neutrophil count in bronchoalveolar lavage fluid, increased the number of macrophages containing apoptotic neutrophils, and prevented inflammatory lung injury. Thus, Rab11a inactivation in macrophages as a result of apoptotic cell binding initiates phagocytosis of apoptotic neutrophils via the modulation of ADAM17-mediated CD36 cell surface expression. Our results raise the possibility that inhibition of Rab11a activity in macrophages is a promising strategy for activating the resolution of inflammatory lung injury.



http://ift.tt/2lh079p

PRMT5-Selective Inhibitors Suppress Inflammatory T Cell Responses and Experimental Autoimmune Encephalomyelitis [AUTOIMMUNITY]

In the autoimmune disease multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), expansion of pathogenic, myelin-specific Th1 cell populations drives active disease; selectively targeting this process may be the basis for a new therapeutic approach. Previous studies have hinted at a role for protein arginine methylation in immune responses, including T cell–mediated autoimmunity and EAE. However, a conclusive role for the protein arginine methyltransferase (PRMT) enzymes that catalyze these reactions has been lacking. PRMT5 is the main PRMT responsible for symmetric dimethylation of arginine residues of histones and other proteins. PRMT5 drives embryonic development and cancer, but its role in T cells, if any, has not been investigated. In this article, we show that PRMT5 is an important modulator of CD4+ T cell expansion. PRMT5 was transiently upregulated during maximal proliferation of mouse and human memory Th cells. PRMT5 expression was regulated upstream by the NF-B pathway, and it promoted IL-2 production and proliferation. Blocking PRMT5 with novel, highly selective small molecule PRMT5 inhibitors severely blunted memory Th expansion, with preferential suppression of Th1 cells over Th2 cells. In vivo, PRMT5 blockade efficiently suppressed recall T cell responses and reduced inflammation in delayed-type hypersensitivity and clinical disease in EAE mouse models. These data implicate PRMT5 in the regulation of adaptive memory Th cell responses and suggest that PRMT5 inhibitors may be a novel therapeutic approach for T cell–mediated inflammatory disease.



http://ift.tt/2lcRLE2

Subclinical Herpes Simplex Virus Type 1 Infections Provide Site-Specific Resistance to an Unrelated Pathogen [MUCOSAL IMMUNOLOGY]

HSV-1 infections of the cornea range in severity from minor transient discomfort to the blinding disease herpes stromal keratitis, yet most patients experience a single episode of epithelial keratitis followed by re-establishment of a clear cornea. We asked whether a single transient episode of HSV-1 epithelial keratitis causes long-term changes in the corneal microenvironment that influence immune responses to subsequent corneal infection or trauma. We showed that C57BL/6 mouse corneas infected with HSV-1 KOS, which induces transient herpes epithelial keratitis without herpes stromal keratitis sequelae, possessed a significant leukocytic infiltrate composed primarily of CD4+ T cells and macrophages along with elevated chemokines and cytokines that persisted without loss of corneal clarity (subclinical inflammation). Chemokine and cytokine expression was CD4+ T cell dependent, in that their production was significantly reduced by systemic CD4+ T cell depletion starting before infection, although short-term (3-d) local CD4+ T cell depletion postinfection did not influence chemokine levels in cornea. Corneas with subclinical inflammation developed significantly greater trauma-induced inflammation when they were recipients of syngeneic corneal transplants but also exhibited significantly increased resistance to infections by unrelated pathogens, such as pseudorabies virus. The resistance to pseudorabies virus was CD4+ T cell dependent, because it was eliminated by local CD4+ T cell depletion from the cornea. We conclude that transient HSV-1 corneal infections cause long-term alterations of the corneal microenvironment that provide CD4-dependent innate resistance to subsequent infections by antigenically unrelated pathogens.



http://ift.tt/2lh7uOe

The Clonal Invariant NKT Cell Repertoire in People with Type 1 Diabetes Is Characterized by a Loss of Clones Expressing High-Affinity TCRs [CLINICAL AND HUMAN IMMUNOLOGY]

Invariant NKT (iNKT) cells in healthy people express iNKT-TCRs with widely varying affinities for CD1d, suggesting different roles for high- and low-affinity iNKT clones in immune regulation. However, the functional implications of this heterogeneity have not yet been determined. Functionally aberrant iNKT responses have been previously demonstrated in different autoimmune diseases, including human type 1 diabetes, but their relationship to changes in the iNKT clonal repertoire have not been addressed. In this study, we directly compared the clonal iNKT repertoire of people with recent onset type 1 diabetes and age- and gender-matched healthy controls with regard to iNKT-TCR affinity and cytokine production. Our results demonstrate a selective loss of clones expressing high-affinity iNKT-TCRs from the iNKT repertoire of people with type 1 diabetes. Furthermore, this bias in the clonal iNKT repertoire in type 1 diabetes was associated with increased GM-CSF, IL-4, and IL-13 cytokine secretion among Ag-stimulated low-affinity iNKT clones. Thus, qualitative changes of the clonal iNKT repertoire with the potential to affect the regulatory function of this highly conserved T cell population are already established at the early stages in type 1 diabetes. These findings may inform future rationales for the development of iNKT-based therapies aiming to restore immune tolerance in type 1 diabetes.



http://ift.tt/2lgXIM6

An Integrated Workflow To Assess Technical and Biological Variability of Cell Population Frequencies in Human Peripheral Blood by Flow Cytometry [NOVEL IMMUNOLOGICAL METHODS]

In the context of large-scale human system immunology studies, controlling for technical and biological variability is crucial to ensure that experimental data support research conclusions. In this study, we report on a universal workflow to evaluate both technical and biological variation in multiparameter flow cytometry, applied to the development of a 10-color panel to identify all major cell populations and T cell subsets in cryopreserved PBMC. Replicate runs from a control donation and comparison of different gating strategies assessed the technical variability associated with each cell population and permitted the calculation of a quality control score. Applying our panel to a large collection of PBMC samples, we found that most cell populations showed low intraindividual variability over time. In contrast, certain subpopulations such as CD56 T cells and Temra CD4 T cells were associated with high interindividual variability. Age but not gender had a significant effect on the frequency of several populations, with a drastic decrease in naive T cells observed in older donors. Ethnicity also influenced a significant proportion of immune cell population frequencies, emphasizing the need to account for these covariates in immune profiling studies. We also exemplify the usefulness of our workflow by identifying a novel cell-subset signature of latent tuberculosis infection. Thus, our study provides a universal workflow to establish and evaluate any flow cytometry panel in systems immunology studies.



http://ift.tt/2lh86Dz

Dysregulation of B Cell Repertoire Formation in Myasthenia Gravis Patients Revealed through Deep Sequencing [CLINICAL AND HUMAN IMMUNOLOGY]

Myasthenia gravis (MG) is a prototypical B cell-mediated autoimmune disease affecting 20–50 people per 100,000. The majority of patients fall into two clinically distinguishable types based on whether they produce autoantibodies targeting the acetylcholine receptor (AChR-MG) or muscle specific kinase (MuSK-MG). The autoantibodies are pathogenic, but whether their generation is associated with broader defects in the B cell repertoire is unknown. To address this question, we performed deep sequencing of the BCR repertoire of AChR-MG, MuSK-MG, and healthy subjects to generate ~518,000 unique VH and VL sequences from sorted naive and memory B cell populations. AChR-MG and MuSK-MG subjects displayed distinct gene segment usage biases in both VH and VL sequences within the naive and memory compartments. The memory compartment of AChR-MG was further characterized by reduced positive selection of somatic mutations in the VH CDR and altered VH CDR3 physicochemical properties. The VL repertoire of MuSK-MG was specifically characterized by reduced V-J segment distance in recombined sequences, suggesting diminished VL receptor editing during B cell development. Our results identify large-scale abnormalities in both the naive and memory B cell repertoires. Particular abnormalities were unique to either AChR-MG or MuSK-MG, indicating that the repertoires reflect the distinct properties of the subtypes. These repertoire abnormalities are consistent with previously observed defects in B cell tolerance checkpoints in MG, thereby offering additional insight regarding the impact of tolerance defects on peripheral autoimmune repertoires. These collective findings point toward a deformed B cell repertoire as a fundamental component of MG.



http://ift.tt/2lcVUrp

Extended phenotype and clinical subgroups in unilateral Meniere disease: a cross-sectional study with cluster analysis

Abstract

Objectives

To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD.

Design

a cross-sectional study with a two-step cluster analysis.

Settings

a tertiary referral multicenter study.

Participants

Nine hundred eighty-eight adult patients with unilateral MD. Main outcome measures: best predictors to define clinical subgroups with potential different etiologies.

Results

We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni and bilateral MD.

Conclusions

Cluster analysis defines clinical subgroups in MD and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomized clinical trials.

This article is protected by copyright. All rights reserved.



http://ift.tt/2lcTvNy

ELMO3 predicts poor outcome in T1 laryngeal cancer

Abstract

Objectives

Despite the excellent overall survival of 92-97% in early glottic cancer, recurrence rates of 13-20% have not improved in the last decades. The engulfment and cell motility protein 3 (ELMO3) has been described as prognostic marker in lung cancer patients. The aim of this study was to investigate the expression of ELMO3 in early laryngeal cancer patients treated with TLM and to evaluate its prognostic significance on clinical outcome.

Design, setting and participant

48 patients with glottic carcinoma (T1N0M0) that underwent primary treatment with TLM between 1994 and 2012 were analyzed. ELMO3 expression of the tumor was assessed using immunohistochemistry and correlated to clinical data.

Main outcome measure

Overall survival (OS), disease specific survival (DSS) and disease-free survival (DFS) rates

Results

Positive ELMO3 expression was found in 23% of the patients and was correlated to poor DSS and DFS (p < 0.05).

Conclusion

This is the first study to show a prognostic effect of positive ELMO3 expression in early glottic carcinoma patients.

This article is protected by copyright. All rights reserved.



http://ift.tt/2kknXmY

Whipple’s disease in granulomatous disguise: a challenging diagnosis with many histopathological pitfalls



http://ift.tt/2keKbEy

Intravenous lidocaine for effective pain relief after bimaxillary surgery

Abstract

Objectives

The aim of this prospective, randomized, double-blind, placebo-controlled study was to evaluate the analgesic effect of intravenous lidocaine on postoperative pain in bimaxillary surgery.

Materials and methods

Between July 2015 and November 2015, 52 consecutive patients that underwent bimaxillary surgery were recruited to the present study. The patients were randomly divided into two groups: group L (1.5 mg/kg bolus and 2 mg/kg/h continuous infusion during the operation) and group C (normal saline). To measure pain intensity, a visual analog scale (VAS) was used at 2, 4, 8, 12, 24, and 48 h after surgery. Rescue ketorolac use was measured in the first 4, 4–8, 8–24, and 24–48 h after surgery. Total ketorolac consumption (the sum of rescue and eight-hourly fixed schedule ketorolac injection), WBC count, neutrophil count, and postoperative swelling were recorded.

Results

There were no significant differences between the two groups with respect to demographics. VAS pain scores were significantly lower in group L compared with group C up to 8 h after surgery. Rescue ketorolac use up to 8 h after surgery and total ketorolac consumption were significantly lower in group L than in group C. Postoperative WBC and neutrophil counts were significantly decreased in group L. Compared with group C, the amount of calibrated postoperative swelling was lower in group L.

Conclusions

Systemic lidocaine infusion during bimaxillary surgery reduces postoperative pain, analgesic consumption, and facial swelling.

Clinical relevance

Systemic lidocaine is simple, economic, and a safe procedure reducing pain and soft tissue swelling after bimaxillary surgery.



http://ift.tt/2kKZJTH

The Utility of Intraoperative Frozen Section for The Evaluation of Microscopic Extrathyroidal Extension in Papillary Thyroid Carcinoma

Abstract

Objectives

This study is designed to evaluate the usefulness of intraoperative frozen section for the evaluation of microscopic extrathyroidal extension (ETE) in papillary thyroid carcinoma (PTC).

Design

Retrospective cohort study.

Setting

Dong-A University Medical Center, Busan, Korea

Participants

Three hundred sixty-four patients who underwent thyroid surgery from January 2000 to December 2010, with PTC confined to one unilateral lobe as diagnosed using preoperative ultrasonography were enrolled.

Main outcome measures

The patients who had microscopic ETE on frozen section were classified into 'group A', and those who did not have microscopic ETE on frozen section were classified into 'group B' Clinicopathologic factors including age, gender, size of the tumor, extent of operation, ETE, multifocality, bilaterality, lymph node metastasis and recurrence were compared between the two groups.

Results

Of the 364 patients enrolled, ETE was confirmed in 100 patients (group A, 27.5%) on frozen biopsy. The nodule size in group A (0.94 ± 0.87 cm) was larger than that in group B (0.86 ± 0.79 cm) (p=0.042). In group A, 15 patients (15%) showed multifocality and 11 patients (14.47%) showed bilaterality. In group B, 37 patients (14.02%) showed multifocality and 7 patients (43.35%) showed bilaterality. They did not differ significantly between the two groups (p=0.811, p=0.182). There was a higher frequency of lymph node metastases in group A (52/86, 60.47%) than in group B (7/16, 43.75%, p=0.214). Recurrence was observed in only two patients who had received thyroid lobectomy as the initial surgery in group A.

Conclusions

Intraoperative frozen biopsy can be an useful method for identifying the microscopic ETE. During the surgery, it can also help the surgeon to decide the optimal extent of surgery and the need for CCND in PTC patients.

This article is protected by copyright. All rights reserved.



http://ift.tt/2kFQjsO

Screening for distress using the distress thermometer and the University of Washington Quality of Life in post-treatment head and neck cancer survivors

Abstract

The primary aim was to determine the efficacy of the Distress Thermometer (DT) in screening for anxiety and mood problems against the University of Washington Quality of Life, version 4 (UWQOL). Secondary aims were to evaluate the association between demographic, clinical and health-related QOL variables with significant distress. Two hundred and sixty one disease-free HNC ambulatory patients attending routine follow-up clinics were prospectively recruited. Both DT and UWQOL were completed pre-consultation. Receiver operating characteristic (ROC) curve analyses of DT score for anxiety dysfunction yielded an area under the curve (AUC) of 0.877, with a sensitivity of 84% (43/51) and specificity of 76% (159/210) for a DT cut-off of ≥4; with a corresponding AUC of 0.825 for mood with sensitivity 78% (28/36) and specificity 71% (159/225). Treatment with radiotherapy and a longer consultation time were associated with significant distress (DT ≥4). Significant distress was also reported in two third of those reporting less than "Good" overall QOL. Distress levels were particularly associated with poor Social–Emotional function, more so than the association seen with poor physical function. DT is a reasonable screening tool for distress in the HNC population. The DT cut-off score ≥4 was effective in identifying those with significant distress. Significant distress is associated in survivors with poor health-related quality of life, those who received radiotherapy and patients who have longer consultation times in clinic.



http://ift.tt/2kFUF3p

Correction: Risk Factors of Early Otitis Media in the Danish National Birth Cohort

by Asbjørn Kørvel-Hanquist, Anders Koch, Janni Niclasen, Jesper Dammeyer, Jørgen Lous, Sjurdur Frodi Olsen, Preben Homøe



http://ift.tt/2kjS79U

Persistent Graves’ hyperthyroidism despite rapid negative conversion of thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results: a case report

Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimul...

http://ift.tt/2jUEXlh

Open reduction with K-wire stabilization of fracture dislocations of the mandibular condyle: A retrospective review

Publication date: Available online 6 February 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Kayvon Haghighi, Manolis G. Manolakakis, Connor Balog
PurposeThe aim of this study is to determine the feasibility of direct transcortical stabilization of fracture dislocations of the mandibular condyle using narrow diameter non threaded K-wireMaterials and MethodsThis retrospective review reports the treatment outcomes for 12 patients (15 fractures) who were treated with open reduction of fracture dislocations of the mandibular condyle (FDMC), using trans-cortical, 0.027" K-wire stabilization. Postoperative parameters of significance included infection, facial nerve function, hardware removal, mandibular range of motion, and radiographic determination of fracture union.Results3 patients with bilateral and 9 with unilateral FDMCs, ages ranging from 14 to 72 at the time of injury, with a mean age of 32. Postoperative follow up ranged from 6 weeks to 2 years. Four patients required removal of K-wire hardware. Hardware removal was for a variety of reasons. K-wires were removed due to infection in one patient. Another patient required removal due to migration of pin into the joint space. One pin was removed electively and another due to non-specific, postoperative symptoms, that resolved after pin removal. Persistent facial nerve deficit was observed in one patient.ConclusionOpen reduction with trans-cortical K-wire stabilization can achieve satisfactory outcomes for the treatment FDMCs. Further investigation is needed in determining the efficacy of this fixation technique in the management of FDMC.



http://ift.tt/2kzMdjy

News and Announcements

Publication date: Available online 5 February 2017
Source:Journal of Oral and Maxillofacial Surgery





http://ift.tt/2kjznax

Galen’s contribution to Head and Neck Surgery

Publication date: Available online 6 February 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Panagiotis Stathopoulos
The historical significance of Galen has always been very high and his works exerted a profound influence on medical thought for over 1300 years. This may be the main reason why his surgical expertise is often neglected. This brief study focuses on the contribution of the distinguished physician to head and neck surgery and it demonstrates that Galen's surgical experience is well documented in his work.



http://ift.tt/2kzRFDj

Interventional repair of pseudoaneurysm of ascending aorta following prosthetic aortic valve replacement

Description

Ascending aorta pseudoaneurysm is a high-risk complication post cardiac surgery.1 Although surgical repair is the conventional method of treatment, it is associated with a high mortality rate of 30% and a very poor prognosis.2 We report an old man aged 85 years who underwent elective biological aortic valve replacement for severe aortic valve stenosis and closure of left atrial appendage with AtriClip. Cardiopulmonary bypass was established with standard ascending aorta and right atrial cannulations. The aortic valve was replaced with 27 mm Hancock II type using 2/0 Ethibond pledgetted sutures in interrupted suture techniques. His medical history included arterial hypertension and atrial fibrillation on rivaroxaban. Despite uneventful postoperative recovery and no symptoms at his follow-up, he presented 4 months later with sternal tenderness and soft tissue swelling at the midpart of sternotomy wound; oral antibiotic was started at that stage and he was discharged home. Two...



http://ift.tt/2lfUQin

Yamaguchi syndrome presenting as atrioventricular nodal re-entrant tachycardia in an African-American patient

Apical hypertrophic cardiomyopathy (Yamaguchi syndrome) is a rare subtype of hypertrophic cardiomyopathy. The syndrome is more common in Japan where it was first described. Outside Asia, it is a very rare cause of hypertrophic cardiomyopathy. Apical hypertrophic cardiomyopathy is usually detected incidentally and has a good long-term outcome. We present a case of apical hypertrophic cardiomyopathy in an African-American patient manifesting as atrioventricular nodal re-entrant tachycardia.



http://ift.tt/2lbTA3T

Primary gastric plasmacytoma: a rare entity

Extramedullary plasmacytomas (EP) are tumours composed by a monoclonal population of plasma cells that arise in extraosseus tissues, comprising <5% of all plasma cell neoplasms. Usually, EP arise in the head and neck region, and the stomach is the second most common location—gastric plasmacytoma (GP). Clinical and radiological manifestations are unspecific and may mimic other tumours like gastric adenocarcinomas, gastric stromal tumours and lymphomas, mainly marginal cell lymphoma (MALT lymphoma) and usually definitive diagnosis is provided by pathological evaluation. We present a case of primary GP, discovered incidentally as a polypoid lesion. Tumour was composed by sheets of mature and immature plasmocytes positive for CD138 on immunohistochemistry, without Helicobacter pylori identification. The patient is alive 6 years later and without tumour relapse.



http://ift.tt/2lgEKG2

Lymphomatoid granulomatosis with pulmonary and gastrointestinal involvement

We present a rare case of grade II lymphomatoid granulomatosis (LYG) with pulmonary and gastrointestinal involvement. LYG is considered an Epstein-Barr virus-driven lymphoproliferative disorder that often presents with multiple nodular lesions in the lungs and sometimes involvement of skin and the central nervous system. Although the aetiology is unknown, it is associated with the use of immunosuppressives. Involvement of other organ systems is very rare. We successfully treated our patients with 6 cycles of R-CHOP and autologous stem cell transplantation with a major response at 20 months follow-up.



http://ift.tt/2lbUNZ9

Implant-associated ESBL-Klebsiella pneumonia producing small colony variant bone and joint infection in a healthy 40-year-old man

Description

A 40-year-old man underwent a bifocal fracture of the left leg in Senegal. An intramedullar rod was implanted to obtain consolidation. At 7 months, the patient was admitted to our institution as the distal fracture had not consolidated (figure 1A). There was no clinical sign of infection. A 1-stage exchange of the rod was performed. No abscess or suspected tissue was detectable during the surgery. Systematic peroperative test of samples were performed, and revealed Klebsiella pneumonia producing extended-spectrum β-lactamase (ESBL), and some colonies expressed the small colony variant (SCV) phenotype in the culture (with the same antibiotic susceptibility), which was also identified to be K. pneumonia (figure 1 B and C). An early new intervention was required due to local abscess formation, the rod was explanted, the tibia was immobilised with a cruro-pedal cast and negative pressure therapy on the skin defect was instaured....



http://ift.tt/2lgYR75

Robotic partial nephrectomy for duplex kidney with ectopic ureter draining in the vagina in an adult patient with urinary incontinence

A duplex kidney system with an ectopic ureter draining into the vagina is a congenital malformation that typically presents as refractory urinary incontinence. Diagnosis is often difficult to establish and delayed due to a low incidence. We present the case of a patient aged 26 years with a life-long history of persistent urinary incontinence. Initial presentation was at childhood; however, the diagnosis went undetermined for 22 years. CT urography revealed a duplex kidney with an atrophic upper pole associated with an ectopic ureter that drained into the vaginal vault. This is the first description of such a case being managed successfully via a robot-assisted partial nephrectomy approach. Ectopic ureteral duplication should be considered in the differential diagnosis for young women with refractory urinary incontinence. Robotic partial nephrectomy is a safe and effective technique to manage such cases.



http://ift.tt/2lbVLV0

Uncommon cause of adult onset cyanosis: single left ventricle

Description

A native American man aged 41 years presented with progressive shortness of breath and discolouration of his lips. Physical examination was significant for central cyanosis and clubbing. Given his cardiac history, echocardiogram and cardiac MRI were ordered to look at the cardiac anatomy and physiology. MRI revealed that the patient has laevorotation of the heart with the cardiac apex pointing posterior to the left midaxillary line with double-inlet morphologic left ventricle (DILV), which was enlarged and hypertrophied. There was a hypoplastic right ventricle which lies superior and anterior to the morphologic left ventricle with large ventricular septal defect. The aorta arises from the hypoplastic right ventricle and courses anterior and to the left of the pulmonary arteries (figures 1–3). There is no pulmonary stenosis or subpulmonary stenosis noted on transthoracic echocardiography, which makes this case even more unique given that is...



http://ift.tt/2lgWiC3

Non-malignant superior vena cava syndrome in a patient with incidental diagnosis of a congenital vascular defect

Description

An 81-year-old patient came to our clinic referred by his general practitioner to assess the distension of the veins in the neck and chest (figure 1). He was asymptomatic, except for the swollen collateral veins in the chest wall. He had no dyspnoea, cough or facial oedema. He had a several-year history of progressively enlarging veins over the anterior chest wall (since the age of 30 years), but he had never sought medical advice. The rest of the physical examination was normal. A chest CT scan showed a persistent left superior vena cava draining into the coronary sinus, chronic thrombosis of the right superior vena cava and venous collateral circulation in the chest (figure 2). The radiologist labelled the thrombosis as chronic, given the decreased venous diameter and the calcified, dense, heterogeneous thrombus.

Figure 1

On physical examination, the patient presented with venous...



http://ift.tt/2lbX1rl

Functional mitral stenosis: a result of bacterial endocarditis

Description

A 72-year-old man received a non-emergent drug-eluting stent to mid-right coronary artery (RCA) for chest pain. He represented 3 weeks later with congestive cardiac failure and rigours. Blood cultures grew Streptococcus sanguinis (viridans); there was no history of rheumatic disease; however, a root canal abscess was treated 3 months prior. Transthoracic echocardiograms (TTE) revealed a thickened anterior mitral valve (MV) and posterior directed jet of mitral regurgitation as well as thickened, restricted posterior mitral valve leaflet (PMVL) with an insignificant gradient of 3 mm Hg. Transoesophageal echocardiogram (TOE) revealed a large 3.0x1.5 cm anterior MV vegetation causing functional mitral stenosis (MS) with a mean gradient of 10 mm Hg (figure 1). He went on to receive a mechanical MV replacement 5 days after diagnosis.

Figure 1

Transoesophageal echocardiogram findings: (A) mid-oesophageal four chamber view showing 3.0x1.5 cm anterior mitral valve vegetation, (B) mid-oesophageal at 54° showing larger anterior mitral valve leaflet vegetation, (C)...



http://ift.tt/2lgHsLS