OtoRhinoLaryngology by Alexandros G.Sfakianakis

Πέμπτη 4 Αυγούστου 2016

Prophylactic Antibiotic Therapy for Preventing Poststroke Infection.

Prophylactic Antibiotic Therapy for Preventing Poststroke Infection.

Neurotherapeutics. 2016 Aug 2;

Authors: Schwarz S

Abstract
Infections, in particular pneumonia, are common complications in patients with acute stroke and are associated with a less favorable neurologic and functional outcome. Patients with severe stroke and dysphagia are at highest risk of infection. Experimental and clinical data suggest stroke-induced immunodeficiency as a major factor contributing to the high incidence of infection after stroke. Preclinical studies support the potential benefit of preventive antibiotic therapy in acute stroke for lowering the incidence of infection and improving clinical outcome. Several smaller clinical trials on preventive antibiotic therapy in patients with stroke conducted during the last 10 years yielded inconclusive results. Recently, 2 large, open-label, controlled trials failed to demonstrate an improved clinical outcome after preventive antibiotic therapy in patients with acute stroke treated in specialized stroke units. In the "Preventive Antibiotics in Stroke Study", antibiotic therapy lowered the rate of infection but did not influence outcome. In the STROKE-INF study, performed in patients with dysphagia after stroke, antibiotic therapy did not lower the incidence of pneumonia and had no prognostic significance. At present, preventive antibiotic therapy cannot be recommended as a therapeutic option for acute stroke.

PMID: 27485236 [PubMed - as supplied by publisher]

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Mediastinal chyloma after lung cancer surgery: case report.

Mediastinal chyloma after lung cancer surgery: case report.

J Cardiothorac Surg. 2016;11(1):115

Authors: Furukawa M, Tao H, Tanaka T, Okabe K

Abstract
BACKGROUND: Chylothorax is a relatively rare but well-known complication of thoracic surgery.
CASE PRESENTATION: A 70-year-old man underwent right upper and middle bilobectomy and systematic lymph node dissection through a posterolateral thoracotomy for lung cancer. On the second postoperative day, he developed chylothorax that was treated with dietary management and pleurodesis. The discharge diminished and his chest tube was removed on the ninth postoperative day. On the 14(th) postoperative day, the patient complained of dyspnea and dysphagia, and imaging studies revealed mediastinal chyloma. Thoracoscopic surgical drainage was performed and the site of chyle leakage was sutured.
CONCLUSIONS: This report presents an unexpected complication of chemical pleurodesis and reviews the indications for surgical intervention in cases of postoperative chylothorax.

PMID: 27484182 [PubMed - in process]

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A meta-analysis of long follow-up outcomes of laparoscopic Nissen (total) versus Toupet (270°) fundoplication for gastro-esophageal reflux disease based on randomized controlled trials in adults.

A meta-analysis of long follow-up outcomes of laparoscopic Nissen (total) versus Toupet (270°) fundoplication for gastro-esophageal reflux disease based on randomized controlled trials in adults.

BMC Gastroenterol. 2016;16(1):88

Authors: Du X, Hu Z, Yan C, Zhang C, Wang Z, Wu J

Abstract
BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is the most common surgical procedure for the surgical management of gastro-esophageal reflux disease (GERD). Laparoscopic Toupet fundoplication (LTF) has been reported to have a lower prevalence of postoperative complications yet still obtain a similar level of reflux control. We conducted a meta-analysis to confirm the value of LNF and LTF.
METHODS: PubMed, Medline, Embase, Cochrane Library and Springerlink were searched for randomized controlled trials (RCTs) comparing LNF and LTF. Data regarding the benefits and adverse results of two techniques were extracted and compared using a meta-analysis.
RESULTS: Eight eligible RCTs comparing LNF (n = 625) and LTF (n = 567) were identified. There were no significant differences between LNF and LTF with regard to hospitalization duration, perioperative complications, patient satisfaction, postoperative heartburn, regurgitation, postoperative DeMeester scores, or esophagites. A shorter operative time and higher postoperative lower esophageal sphincter pressure were associated with LNF. Prevalence of postoperative dysphagia, gas-bloating, inability to belch, dilatation for dysphagia and reoperation were higher after LNF, but subgroup analyses showed that differences with respect to dysphagia between LNF and LTF disappeared over time. Subgroup analyses did not support "tailored therapy" according to preoperative esophageal motility.
CONCLUSIONS: LNF and LTF have equivalently good control of GERD and result in a similar prevalence of patient satisfaction. Based on current evidence, it is not rational or advisable to abandon LNF when choosing a surgical procedure for GERD.

PMID: 27484006 [PubMed - in process]

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Prevention team.

Prevention team.

BMJ. 2016;352:i1680

Authors: Hawkes N

PMID: 27012884 [PubMed - indexed for MEDLINE]

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The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation.

The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation.

Mol Biol Cell. 2015 Oct 1;26(19):3424-38

Authors: Carvalhal S, Ribeiro SA, Arocena M, Kasciukovic T, Temme A, Koehler K, Huebner A, Griffis ER

Abstract
The formation of the mitotic spindle is a complex process that requires massive cellular reorganization. Regulation by mitotic kinases controls this entire process. One of these mitotic controllers is Aurora A kinase, which is itself highly regulated. In this study, we show that the nuclear pore protein ALADIN is a novel spatial regulator of Aurora A. Without ALADIN, Aurora A spreads from centrosomes onto spindle microtubules, which affects the distribution of a subset of microtubule regulators and slows spindle assembly and chromosome alignment. ALADIN interacts with inactive Aurora A and is recruited to the spindle pole after Aurora A inhibition. Of interest, mutations in ALADIN cause triple A syndrome. We find that some of the mitotic phenotypes that we observe after ALADIN depletion also occur in cells from triple A syndrome patients, which raises the possibility that mitotic errors may underlie part of the etiology of this syndrome.

PMID: 26246606 [PubMed - indexed for MEDLINE]

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Hyperplastic stomatitis and esophagitis in a tortoise (Testudo graeca) associated with an adenovirus infection.

Hyperplastic stomatitis and esophagitis in a tortoise (Testudo graeca) associated with an adenovirus infection.

J Vet Diagn Invest. 2016 Aug 2;

Authors: Garcia-Morante B, Pénzes JJ, Costa T, Martorell J, Martínez J

Abstract
A 2-year-old female, spur-thighed tortoise (Testudo graeca) was presented with poor body condition (1/5) and weakness. Fecal analysis revealed large numbers of oxyurid-like eggs, and radiographs were compatible with gastrointestinal obstruction. Despite supportive medical treatment, the animal died. At gross examination, an intestinal obstruction was confirmed. Histopathology revealed severe hyperplastic esophagitis and stomatitis with marked epithelial cytomegaly and enormous basophilic intranuclear inclusion bodies. Electron microscopy examination revealed a large number of 60-80 nm, nonenveloped, icosahedral virions arranged in crystalline arrays within nuclear inclusions of esophageal epithelial cells, morphologically compatible with adenovirus-like particles. PCR for virus identification was performed with DNA extracted from formalin-fixed, paraffin-embedded tissues. A nested, consensus pan-adenovirus PCR and sequencing analysis showed a novel adenovirus. According to phylogenetic calculations, it clustered to genus Atadenovirus in contrast with all other chelonian adenoviruses described to date. The present report details the pathologic findings associated with an adenovirus infection restricted to the upper digestive tract.

PMID: 27486139 [PubMed - as supplied by publisher]

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Somatic mosaicism in B cells of a patient with autosomal dominant hyper IgE syndrome

Hyper IgE syndrome (HIES) is characterized by recurrent skin abscesses, eczema, pneumonia, and high levels of serum IgE. Non-immunologic manifestations of HIES include a characteristic face, pathologic dentition, scoliosis, bone alterations, hyperextensible joints, and vascular abnormalities. Somatic mosaicism is defined by the presence of two or more populations of cells with different genotypes in one individual. In this report we describe one patient with classical HIES and another patient with a mild phenotype, both harboring the same genetic mutation. The patient with a mild phenotype did not present the characteristic face, had normal production of IL-17A by T CD4⁺ cells, but had low phosphorylation of STAT-3 in B cells. Interestingly, the mutation found in B cells was absent in other cell types analyzed, in agreement with the presence of a somatic mosaic genotype. The clinical and functional differences observed between these patients justify the use of complementary tools for a better definition of the cases. These approaches allow for a better understanding of complex phenotypes associated with somatic mosaicisms, and present the possibility to analyze the role of B lymphocytes in the pathophysiology of this disease. This knowledge has an impact on not only the treatment but also the provision of appropriate genetic counseling.

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Effects of Change in Tongue Pressure and Salivary Flow Rate on Swallow Efficiency Following Chemoradiation Treatment for Head and Neck Cancer

Abstract

Patients treated with chemoradiation for head and neck cancer frequently develop dysphagia. Tissue damage to the oral tongue causing weakness along with decreases in saliva production may contribute to dysphagia. Yet, effects of these variables on swallowing-related measures are unclear. The purpose of this study was (1) to determine effects of chemoradiation on tongue pressures, as a surrogate for strength, and salivary flow rates and (2) to elucidate relationships among tongue pressures, saliva production, and swallowing efficiency by bolus type. Twenty-one patients with head and neck cancer treated with chemoradiation were assessed before and after treatment and matched with 21 healthy control participants who did not receive chemoradiation. Each participant was given a questionnaire to rate dysphagia symptoms. Videofluoroscopic Evaluation of Swallowing (VFES) was used to determine swallowing efficiency; the Saxon test measured salivary flow rate; and the Iowa Oral Performance Instrument (IOPI) was used for oral tongue maximum and endurance measures. Results revealed significantly lower tongue endurance measures for patients post-treatment as compared to controls (p = .012). Salivary flow rates also were lower compared to pre-treatment (p = .000) and controls (p = .000). Simple linear regression analyses showed that change in salivary flow rate was predictive of change in swallow efficiency measures from pre- to post-treatment for 1 mL thin liquid (p = .017), 3 mL nectar-thick liquid (p = .026), and 3 mL standard barium pudding (p = .011) boluses. Based on these findings, it appears that chemoradiation treatment affects tongue endurance and salivary flow rate, and these changes may impact swallow efficiency. These factors should be considered when planning treatment for dysphagia.

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Drugs Related to Oropharyngeal Dysphagia in Older People

Abstract

Scientific evidence on the impact of medication on the physiology of swallowing is scarce and mainly based on clinical case reports. To evaluate the association between oropharyngeal dysphagia (OD) and chronic exposure to medication in older patients admitted to the acute geriatric unit (AGU) of a secondary hospital, we performed a retrospective cross-sectional study of 966 patients admitted to an AGU from 2008 to 2011. We reviewed (a) diagnosis of OD (assessed with the volume-viscosity swallow test, V- VST); (b) chronic patient medication classified by anatomical, therapeutic, chemical codes; and (c) demographic and clinical data. A univariate analysis was performed to determine which medications were associated with OD. A multivariate analysis adjusting for confounding clinical factors was performed to identify which of those medications were independently associated with OD. The age of patients included was 85.3 ± 6.37 years and 59.4 % were women. A total of 41.9 % presented OD. We found a possible protective effect of beta blocking agents on OD after the multivariate analysis (OR 0.54, 95 % CI 0.35–0.85). None of the categories of drugs was associated with an altered swallowing function after adjusting for confounding variables. The present study is the first one to widely investigate the association between drugs and OD, increasing understanding of their association. The role of beta blockers in OD needs to be further studied as their potentially beneficial effects on the swallowing function in older patients could help to prevent complications.

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Treatment Effects for Dysphagia in Adults with Multiple Sclerosis: A Systematic Review

Abstract

Dysphagia or swallowing difficulties have been reported to be a concern in adults with multiple sclerosis (MS). This problem can result in several complications including aspiration pneumonia, reduced quality of life and an increase in mortality rate. No previous systematic reviews on treatment effects for dysphagia in MS have been published. The main objective of this study is to summarise and qualitatively analyse published studies on treatment effects for dysphagia in MS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied to conduct a systematic search of seven databases, using relevant key words, and subsequent analysis of the identified studies. The studies were required to meet all three inclusion criteria of including a statement on intention to treat, or measure the effects of treatment for dysphagia in adults with MS and data on treatment outcomes for at least one adult diagnosed with MS. Retained studies were evaluated by two independent reviewers using a critical appraisal tool. This study has not been registered. A total of 563 studies were identified from the database searches. After screening and assessment of full articles for eligibility, five studies were included in the review. Three examined electrical stimulation and two examined the use of botulinum toxin. One study testing electrical stimulation was a randomised controlled trial, two were well-designed case series and two were case series lacking experimental control. All studies reported some positive effects on dysphagia; however, treatments that involved the use of electrical stimulation showed larger effect sizes. There is a paucity of evidence to guide treatment of dysphagia in MS, with only electrical stimulation and botulinum toxin treatment represented in the literature search conducted here. While both treatments show initial promise for reducing the swallowing impairment, they require further research using well-controlled experimental designs to determine their clinical applicability and long-term treatment effects for dysphagia across different types and severity of MS.

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Oral mucositis associated with cancer therapy. Guide to first-choice treatments.

Oral mucositis associated with cancer therapy. Guide to first-choice treatments.

Prescrire Int. 2016 Jun;25(172):155-6

Authors:

PMID: 27486648 [PubMed - in process]

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Therapeutic Management of Feline Chronic Gingivostomatitis: A Systematic Review of the Literature.

Therapeutic Management of Feline Chronic Gingivostomatitis: A Systematic Review of the Literature.

Front Vet Sci. 2016;3:54

Authors: Winer JN, Arzi B, Verstraete FJ

Abstract
Feline chronic gingivostomatitis (FCGS) is a disease characterized by protracted and potentially debilitating oral inflammation in cats, the etiology of which is currently unknown. The purpose of this review is to apply an evidence-based medicine approach to systematically review and critically evaluate the scientific literature reporting the outcome of medical and surgical management of FCGS. Those articles meeting inclusion criteria were reviewed and assigned an "Experimental Design Grade" (EDG) and an "Evidence Grade" (EG) in order to score relative strength of study design and produced data. Studies were evaluated and compared, especially highlighting the treatments, the outcomes, and the therapeutic success rates. This review found a lack of consistency between articles' data, rendering direct comparison of results unreliable. The field of FCGS research, and ultimately patient care, would benefit from standardizing studies by adopting use of a consistent semi-quantitative scoring system and extending follow-up duration. Future researchers should commit to large prospective studies that compare existing treatments and demonstrate the promise of new treatments.

PMID: 27486584 [PubMed]

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Inhibitory effects of an aqueous extract from Cortex Phellodendri on the growth and replication of broad-spectrum of viruses in vitro and in vivo.

Inhibitory effects of an aqueous extract from Cortex Phellodendri on the growth and replication of broad-spectrum of viruses in vitro and in vivo.

BMC Complement Altern Med. 2016;16(1):265

Authors: Kim JH, Weeratunga P, Kim MS, Nikapitiya C, Lee BH, Uddin MB, Kim TH, Yoon JE, Park C, Ma JY, Kim H, Lee JS

Abstract
BACKGROUND: Cortex Phellodendri (C. Phellodendri), the dried trunk bark of Phellodendron amurense Ruprecht, has been known as a traditional herbal medicine, showing several bioactivities. However, antiviral activity of C. Phellodendri aqueous extract (CP) not reported in detail, particularly aiming the prophylactic effectiveness.
METHODS: In vitro CP antiviral activity evaluated against Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Newcastle Disease Virus (NDV), Herpes Simplex Virus (HSV), Coxsackie Virus (H3-GFP) and Enterovirus-71 (EV-71) infection on immune (RAW264.7) and epithelial (HEK293T/HeLa) cells. Such antiviral effects were explained by the induction of antiviral state which was determined by phosphorylation of signal molecules, secretion of IFNs and cytokines, and cellular antiviral mRNA expression. Furthermore, Compounds present in the aqueous fractions confirmed by HPLC analysis and evaluated their anti-viral activities. Additionally, in vivo protective effect of CP against divergent influenza A subtypes was determined in a BALB/c mouse infection model.
RESULTS: An effective dose of CP significantly reduced the virus replication both in immune and epithelial cells. Mechanically, CP induced mRNA expression of anti-viral genes and cytokine secretion in both RAW264.7 and HEK293T cells. Furthermore, the main compound identified was berberine, and shows promising antiviral properties similar to CP. Finally, BALB/c mice treated with CP displayed higher protection levels against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2).
CONCLUSION: CP including berberine play an immunomodulatory role with broad spectrum antiviral activity, due to induction of antiviral state via type I IFN stimulation mechanism. Consequently, C. Phellodendri could be a potential source for promising natural antivirals or to design other antiviral agents for animal and humans.

PMID: 27484768 [PubMed - in process]

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Effects of Change in Tongue Pressure and Salivary Flow Rate on Swallow Efficiency Following Chemoradiation Treatment for Head and Neck Cancer

Abstract

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Drugs Related to Oropharyngeal Dysphagia in Older People

Abstract

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Treatment Effects for Dysphagia in Adults with Multiple Sclerosis: A Systematic Review

Abstract

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Will the mininvasive approach challenge the old paradigms in oral cancer surgery?

Abstract

In the genome era, the achievement of a safe and complete resection of oral cancers remains a challenge for surgeons. Margin length at histopathological examination is still considered the main indicator of oncological radicality. However, this parameter is fraught by major limitations. Cancer aggressiveness, and in particular its ability to spread in the surrounding tissue, most probably influences loco-regional control and prognosis more than margin length. Unfortunately, no molecular markers are currently available to predict tumor aggressiveness pre-operatively. However, additional histopathological parameters, beside margin length, could be considered to better stratify oral tumors, including depth of invasion (DOI), perineural invasion or composite scores. Recent advances in laser technology have established a novel surgical trend toward a minimalist approach, named transoral laser microsurgery (TLM). TLM provides a local control rate comparable to the one achieved by larger resections if the margin appears disease free, independent from its length. In addition, the clinical availability of innovative optical technologies, such as narrow band imaging (NBI) or autofluorescence, allows more precise and tailored resections, not simply based on clinical observation and ruler measurement. This review will propose the possible implementation of novel procedures toward a mini-invasive surgical approach, providing a satisfactory control rate but significantly improving the quality of life of the patients compared to conventional surgery.

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Primary surgery results in no survival benefit compared to primary radiation for oropharyngeal cancer patients stratified by high-risk human papilloma virus status

Abstract

We changed the primary oropharynx squamous cell carcinoma (OPSCC) treatment recommendation from primary radiation therapy (RT) to tumor surgery and neck dissection, followed by RT around the year 2000 with apparently improved survival. However, high-risk human papilloma virus (hr-HPV)-16-caused OPSCCs have increased during this period. Furthermore, hr-HPV+ OPSCC carry a better prognosis than hr-HPV-negative patients. We have, therefore, evaluated the 5-year survival in the period from 1992 to 1999 versus 2000 to 2008 stratified by hr-HPV tumor infection status. Ninety-six OPSCC patients were treated from 1992 to 1999 compared with 136 patients from 2000 to 2008. The 5-year disease-specific survival (DDS) and overall survival (OS) were recorded, while the health-related quality of life (HRQoL) scores were obtained from some of the cured patients. Thirty-eight (40 %) in the first period and 86 OPSCCs (63 %) in the second period were hr-HPV+. In the first period, 16 versus 62 patients in the last period were treated by neck dissection, primary tumor surgery, and RT. DSS among all the hr-HPV-negative patients in the first period was 51 versus 55 % in the second period, and the corresponding OS was 33 versus 31 %, respectively. The DSS among all the hr-HPV+ patients was 78 % in the first period versus 77 % in the second period, while the OS was 71 versus 69 %, respectively. The HRQoL scores among successfully treated patients were worse following surgery, plus RT than RT only. The hr-HPV-adjusted 5-year survival in OPSCC patients was similar between the two time periods. A decreased HRQoL was associated with surgical therapy, which indicates that hr-HPV+ OPSCC patients may be treated by primary RT followed by major surgery only if RT treatment fails.

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Modulation of nociceptive threshold by combined hormonal contraceptives in women with oestrogen-withdrawal migraine attacks: a pilot study

Menstrually-related headache and headaches associated with oestrogen withdrawal are common conditions, whose pathophysiology has not been completely elucidated. In this study we evaluated the influence of comb...

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Binding of estrogen receptors to switch sites and regulatory elements in the immunoglobulin heavy chain locus of activated B cells suggests a direct influence of estrogen on antibody expression

Publication date: September 2016
Source:Molecular Immunology, Volume 77
Author(s): Bart G. Jones, Rhiannon R. Penkert, Beisi Xu, Yiping Fan, Geoff Neale, Patricia J. Gearhart, Julia L. Hurwitz
Females and males differ in antibody isotype expression patterns and in immune responses to foreign- and self-antigens. For example, systemic lupus erythematosus is a condition that associates with the production of isotype-skewed anti-self antibodies, and exhibits a 9:1 female:male disease ratio. To explain differences between B cell responses in males and females, we sought to identify direct interactions of the estrogen receptor (ER) with the immunoglobulin heavy chain locus. This effort was encouraged by our previous identification of estrogen response elements (ERE) in heavy chain switch (S) regions. We conducted a full-genome chromatin immunoprecipitation analysis (ChIP-seq) using DNA from LPS-activated B cells and an ERα-specific antibody. Results revealed ER binding to a wide region of DNA, spanning sequences from the JH cluster to Cδ, with peaks in Eμ and Sμ sites. Additional peaks of ERα binding were coincident with hs1,2 and hs4 sites in the 3′ regulatory region (3′RR) of the heavy chain locus. This first demonstration of direct binding of ER to key regulatory elements in the immunoglobulin locus supports our hypothesis that estrogen and other nuclear hormone receptors and ligands may directly influence antibody expression and class switch recombination (CSR). Our hypothesis encourages the conduct of new experiments to evaluate the consequences of ER binding. A better understanding of ER:DNA interactions in the immunoglobulin heavy chain locus, and respective mechanisms, may ultimately translate to better control of antibody expression, better protection against pathogens, and prevention of pathologies caused by auto-immune disease.

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Evidences of abundant hemocyanin variants in shrimp Litopenaeus vannamei

Publication date: September 2016
Source:Molecular Immunology, Volume 77
Author(s): Xianliang Zhao, Lingling Guo, Xin Lu, Hui Lu, Fan Wang, Mingqi Zhong, Jiehui Chen, Yueling Zhang
Hemocyanin (HMC) is a multifunctional immune molecule present in mollusks and arthropods and functions as an important antigen non-specific immune protein. Our previous evidences demonstrated that Litopenaeus vannamei HMC might display extensive molecular diversities. In this study, bioinformatics analysis showed dozens of variant sequences of the HMC subunit with higher molecular weight from L. vannamei (LvHMC). Three variant fragments, named as LvHMCV1-3, which shared 85–99% nucleotide identity with that of the classical form of LvHMC (AJ250830.1), were cloned and characterized. Spatial expression profiles showed that LvHMCV1-3 had different tissue-specific distribution, which were affected by stimulation with six pathogenic bacteria, including Escherichia coli K12, Vibrio parahaemolyticus, Vibrio alginolyticus, Vibrio fluvialis, Streptococcus pyogenes and Staphylococcus aureus, with each variant fragment showing a specific stress pattern to different bacterial pathogens. Full length cDNA of LvHMCV3 was further cloned and characterized. The deduced amino acid sequence shared 92% identity with that of LvHMC, possessed a conserved structure characteristic of the HMC family and could be clustered into one branch along with other arthropod HMC in a phylogenetic tree. In addition, the recombinant protein of LvHMCV3 (rLvHMCV3) showed obvious agglutination activities against three aquaculture pathogenic bacteria including E. coli K12, V. parahaemolyticus and S.aureus at concentrations ranging from 31.25–62.5g/mL. It also showed obvious antibacterial activity against V. parahaemolyticus at concentrations 0.02–0.5mg/mL, and possessed the best inhibitive effects compared with those of rLvHMCV4 and rLvHMC. Co-injection of V. parahaemolyticus and rLvHMCV3 in L. vannamei showed significant decrease of the mortality rate at 24–72h after injection. Therefore, these studies suggested that L. vannamei had abundant HMC variants, which possessed obvious resistance to pathogenic infection and might specifically target on different pathogens in shrimp.

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Exceptionally long CDR3H of bovine scFv antigenized with BoHV-1 B-epitope generates specific immune response against the targeted epitope

Publication date: September 2016
Source:Molecular Immunology, Volume 77
Author(s): Yfke Pasman, Caroline Soliman, Paul A. Ramsland, Azad K. Kaushik
We discovered that some bovine antibodies are amongst the largest known to exist due to the presence of an exceptionally long CDR3H (≥49 amino acids) with multiple cysteines that provide a unique knob and stalk structure to the antigen binding site. The large CDR3H size, unlike mouse and human, provides a suitable platform for antigenization with large configurational B-epitopes. Here we report the identification of a B-epitope on the gC envelope protein of bovine herpes virus type-1 (BoHV-1) recognized by a bovine IgG1 antibody. The identified 156 amino acid long gC fragment (gC156) was expressed as a recombinant protein. Subsequently, a functional scFv fragment with a 61 amino-acid long CDR3H (scFv1H12) was expressed such that gC156 was grafted into the CDR3H, replacing the "knob" region (gC156scFv1H12 or Ag-scFv). Importantly, the Ag-scFv could be recognized by a neutralizing antibody fragment (scFv3-18L), which suggests that the engraftment of gC156 into the CDR3H of 1H12 maintained the native conformation of the BoHV-1 B-epitope. A 3D model of gC156 was generated using fold-recognition approaches and this was grafted onto the CDR3H stalk of the 1H12 Fab crystal structure to predict the 3D structure of the Ag-scFv. The grafted antigen in Ag-scFv is predicted to have a compact conformation with the ability to protrude into the solvent. Upon immunization of bovine calves, the antigenized scFv (gC156scFv1H12) induced a higher antibody response as compared to free recombinant gC156. These observations suggest that antigenization of bovine scFv with an exceptionally long CDR3H provides a novel approach to developing the next generation of vaccines against infectious agents that require induction of protective humoral immunity.

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Modulation of nociceptive threshold by combined hormonal contraceptives in women with oestrogen-withdrawal migraine attacks: a pilot study

Binding of estrogen receptors to switch sites and regulatory elements in the immunoglobulin heavy chain locus of activated B cells suggests a direct influence of estrogen on antibody expression

Evidences of abundant hemocyanin variants in shrimp Litopenaeus vannamei

Exceptionally long CDR3H of bovine scFv antigenized with BoHV-1 B-epitope generates specific immune response against the targeted epitope

Frequency discrimination in the common marmoset (Callithrix jacchus)

Publication date: Available online 3 August 2016
Source:Hearing Research
Author(s): Michael S. Osmanski, Xindong Song, Yueqi Guo, Xiaoqin Wang
The common marmoset (Callithrix jacchus) is a highly vocal New World primate species that has emerged in recent years as a promising model system for studies of auditory and vocal processing. Our recent studies have examined perceptual mechanisms related to the pitch of harmonic complex tones in this species. However, no previous psychoacoustic work has measured marmosets' frequency discrimination abilities for pure tones across a broad frequency range. Here we systematically examined frequency difference limens (FDLs), which measure the minimum discriminable frequency difference between two pure tones, in marmosets across most of their hearing range. Results show that marmosets' FDLs are comparable to other New World primates, with lowest values in the frequency range of ∼3.5–14 kHz. This region of lowest FDLs corresponds with the region of lowest hearing thresholds in this species measured in our previous study and also with the greatest concentration of spectral energy in the major types of marmoset vocalizations. These data suggest that frequency discrimination in the common marmoset may have evolved to match the hearing sensitivity and spectral characteristics of this species' vocalizations.

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Controlled Exploration of the Effects of Conductive Hearing Loss on Wideband Acoustic Immittance in Human Cadaveric Preparations

Publication date: Available online 3 August 2016
Source:Hearing Research
Author(s): Gabrielle R. Merchant, Saumil N. Merchant, John J. Rosowski, Hideko Heidi Nakajima
Current clinical practice cannot distinguish, with any degree of certainty, the multiple pathologies that produce conductive hearing loss in patients with an intact tympanic membrane and a well-aerated middle ear without exploratory surgery. The lack of an effective non-surgical diagnostic procedure leads to unnecessary surgery and limits the accuracy of information available during pre-surgical consultations with the patient. A non-invasive measurement to determine the pathology responsible for a conductive hearing loss prior to surgery would be of great value. This work investigates the utility of wideband acoustic immittance (WAI), a non-invasive measure of middle-ear mobility, in the differential diagnosis of pathologies responsible for conductive hearing loss.We focus on determining whether power reflectance (PR), a derivative of WAI, is a possible solution to this problem. PR is a measure of the fraction of sound power reflected from the middle ear when a sound stimulus is presented to the ear canal. PR and other metrics of middle-ear performance (such as ossicular motion via laser Doppler vibrometry) were measured in well-controlled human temporal bone preparations with simulated pathologies. We report measurements before and after simulation of stapes fixation (n=8), malleus fixation (n=10), ossicular disarticulation (n=10), and superior canal dehiscence (n=8). Our results are consistent with the small set of previously published reflectance measurements made in temporal bones and patients. In this present study, these temporal bone experiments with different middle- and inner-ear pathologies were compared to the initial normal state by analyzing both WAI and ossicular motion, demonstrating that WAI can be a valuable tool in the diagnosis of conductive hearing loss.

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Vestibular-dependent inter-stimulus interval effects on sound evoked potentials of central origin

Publication date: Available online 3 August 2016
Source:Hearing Research
Author(s): N.P.M. Todd, S. Govender, J.G. Colebatch
Todd et al. (2014ab) have recently demonstrated the presence of vestibular-dependent contributions to auditory evoked potentials (AEPs) when passing through the vestibular threshold as determined by vestibular evoked myogenic potentials (VEMPs), including a particular deflection labeled as an N42/P52 prior to the long-latency AEPs N1 and P2. In this paper we report the results of an experiment to determine the effect of inter-stimulus interval (ISI) and regularity on potentials recorded above and below VEMP threshold. Five healthy, right-handed subjects were recruited and evoked potentials were recorded to binaurally presented sound stimulation, above and below vestibular threshold, at seven stimulus rates with ISIs of 212, 300, 424, 600, 848, 1200 and 1696 ms. The inner five intervals, i.e. 300, 424, 600, 848, 1200 ms, were presented twice in both regular and irregular conditions. ANOVA on the global field power (GFP) were conducted for each of four waves, N42, P52, N1 and P2 with factors of intensity, ISI and regularity. Both N42 and P52 waves showed significant ANOVA effects of intensity but no other main effects or interactions. In contrast both N1 and P2 showed additional effects of ISI, as well as intensity, and evidence of non-linear interactions between ISI and intensity. A source analysis was carried out consistent with prior work suggesting that when above vestibular threshold, in addition to bilateral superior temporal cortex, ocular, cerebellar and cingulate sources are recruited. Further statistical analysis of the source currents indicated that the origin of the interactions with intensity may be the ISI sensitivity of the vestibular-dependent sources. This in turn may reflect a specific vestibular preference for stimulus rates associated with locomotion, i.e. rates close to 2 Hz, or ISIs close to 500 ms, where saccular afferents show increased gain and the corresponding reflexes are most sensitive.

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Drug discovery for hearing loss: Phenotypic screening of chemical compounds on primary cultures of the spiral ganglion

Publication date: Available online 2 August 2016
Source:Hearing Research
Author(s): Donna S. Whitlon
In the United States there are, at present, no drugs that are specifically FDA approved to treat hearing loss. Although several clinical trials are ongoing, including one testing D-methionine that is supported by the US Army, none of these trials directly address the effect of noise exposure on cochlear spiral ganglion neurons. We recently published the first report of a systematic chemical compound screen using primary, mammalian spiral ganglion cultures in which we were able to detect a compound and others in its class that increased neurite elongation, a critical step in restoring cochlear synapses after noise induced hearing loss. Here we discuss the issues, both pro and con, that influenced the development of our approach. These considerations may be useful for future compound screens that target the same or other attributes of cochlear spiral ganglion neurons.

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Does the degree of linguistic experience (native versus nonnative) modulate the degree to which listeners can benefit from a delay between the onset of the maskers and the onset of the target speech?

Publication date: Available online 2 August 2016
Source:Hearing Research
Author(s): Boaz M. Ben-David, Meital Avivi-Reich, Bruce A. Schneider
Background noise has a greater adverse effect on word recognition when people are listening in their second language (L2) as opposed to their first language (L1). The present study investigates the extent to which linguistic experience affects the ability of L2 listeners to benefit from a delay between the onset of a masker and the onset of a word. In a previous study (Ben-David, Tse & Schneider, 2012), word recognition thresholds for young L1s were found to improve with the increase in the delay between the onset of a masker (either a stationary noise or a babble of voices) and the onset of a word. The investigators interpreted this result as reflecting the ability of L1 listeners to rapidly segregate the target words from a masker. Given stream segregation depends, in part, on top-down knowledge-driven processes, we might expect stream segregation to be more "sluggish" for L2 listeners than for L1 listeners, especially when the masker consists of a babble of L2 voices. In the present study, we compared the ability of native English speakers to those who had either recent or long-term immersion in English as L2, to benefit from a delay between masker onset and word onset for English words. Results show that thresholds were higher for the two L2s groups than for the L1s. However, the rate at which word recognition improved with word-onset delay was unaffected by linguistic status, both when words were presented in noise, and in babble. Hence, for young listeners, stream segregation appears to be independent of linguistic status, suggesting that bottom-up sensory mechanisms play a large role in stream segregation in this paradigm. The implications of a failure of older L1 listeners (in Ben-David et al.) to benefit from a word-onset delay when the masker is a babble of voices are discussed.

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Frequency discrimination in the common marmoset (Callithrix jacchus)

Controlled Exploration of the Effects of Conductive Hearing Loss on Wideband Acoustic Immittance in Human Cadaveric Preparations

Vestibular-dependent inter-stimulus interval effects on sound evoked potentials of central origin

Drug discovery for hearing loss: Phenotypic screening of chemical compounds on primary cultures of the spiral ganglion

Does the degree of linguistic experience (native versus nonnative) modulate the degree to which listeners can benefit from a delay between the onset of the maskers and the onset of the target speech?

A case series and a review of the literature on foreign modelling agent reaction: an emerging problem

Abstract

Foreign modelling agent reactions (FMAR) are the result of the injection of unapproved high-viscosity fluids with the purpose of cosmetic body modelling. Its consequences lead to ulceration, disfigurement and even death, and it has reached epidemic proportions in several regions of the world. We describe a series of patients treated for FMARs in a specialised wound care centre and a thorough review of the literature. A retrospective chart review was performed from January 1999 to September 2015 of patients who had been injected with non-medical foreign agents and who developed cutaneous ulceration needing treatment at the dermatology wound care centre. This study involved 23 patients whose ages ranged from 22 to 67 years with higher proportion of women and homosexual men. The most commonly injected sites were the buttocks (38·5%), legs (18%), thighs (15·4%) and breasts (11·8%). Mineral oil (39%) and other unknown substances (30·4%) were the most commonly injected. The latency period ranged from 1 week to 17 years. Complications included several skin changes such as sclerosis and ulceration as well as systemic complications. FMAR is a severe syndrome that may lead to deadly complications, and is still very common in Latin America.

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Heel ulcers do heal in patients with diabetes

Abstract

A heel ulcer is considered to be a serious complication in patients with diabetes, and there is limited information regarding outcome. In most of the literature, a poor prognosis is described. The aim of this study was to investigate a large cohort of ulcers located in the heel in patients with diabetes.

Seven hundred and sixty-eight patients [median age 73 (17–98)], presenting with a heel ulcer at a multidisciplinary diabetes foot clinic, fulfilled the inclusion criteria and were followed-up until final outcome.

Fifty-eight per cent of the patients healed primarily; 7% healed after major debridement; 9% healed after amputation and 25% died unhealed. Median healing time was 17 weeks. Ulcer progression was seen in 19% of patients. Thirty-one percent of patients had severe peripheral vascular disease. A creatinine level below 91 µmol/l was related to a higher probability for healing without major debridement or amputation, whereas vascular surgery, nephropathy and oedema were related to a lower probability for healing without major debridement or amputation.

Two thirds of heel ulcers do heal in patients with diabetes despite patients being elderly and with extensive comorbidity. The extent of peripheral vascular disease, nephropathy, oedema and decreased renal function are important factors influencing outcome.

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The impact of lower limb chronic oedema on patients' quality of life

Abstract

This study aimed to explore patients' perceptions regarding the impact that lower limb chronic oedema has on their quality of life (QoL). A quantitative descriptive design was used to collect data from patients with lower limb chronic oedema. A condition-specific validated questionnaire was distributed to a purposive sample (n = 122) through manual lymphatic drainage/vascular/health clinics in Ireland. Results indicated that patients with lower limb chronic oedema experience a wide range of physical problems such as limb heaviness (74%, n = 66), weakness (44%, n = 40) and pain (38%, n = 34). Additionally, difficulties with walking (53%, n = 48), standing (51%, n = 46) and bending (45%, n = 40) were reported. Concerns regarding poor body image were strongly evident (76%, n = 68). Difficulties finding clothing/footwear to fit oedematous limb(s) were reported (59%, n = 53), in addition to finding clothes that participants would like to wear (64%, n = 58). Emotional symptoms of irritability (42%, n = 38), anxiety (41%, n = 37) and tension (40%, n = 36) were reported. Over half of the participants (55%, n = 49) stated that their chronic swelling affected their social functioning and their ability to engage in leisure activities. This study has identified that lower limb chronic oedema has significant psychological, social and physical implications for persons' QoL.

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A cost-effectiveness analysis of optimal care for diabetic foot ulcers in Australia

Abstract

In addition to affecting quality of life, diabetic foot ulcers (DFUs) impose an economic burden on both patients and the health system. This study developed a Markov model to analyse the cost-effectiveness of implementing optimal care in comparison with the continuation of usual care for diabetic patients at high risk of DFUs in the Australian setting. The model results demonstrated overall 5-year cost savings (AUD 9100·11 for those aged 35–54, $9391·60 for those aged 55–74 and $12 394·97 for those aged 75 or older) and improved health benefits measured in quality-adjusted life years (QALYs) (0·13 QALYs, 0·13 QALYs and 0·16 QALYs, respectively) for high-risk patients receiving optimal care for DFUs compared with usual care. Total cost savings for Australia were estimated at AUD 2·7 billion over 5 years. Probabilistic sensitivity analysis showed that optimal care always had a higher probability of costing less and generating more health benefits. This study provides important evidence to inform Australian policy decisions on the efficient use of health resources and supports the implementation of evidence-based optimal care in Australia. Furthermore, this information is of great importance for comparable developed countries that could reap similar benefits from investing in these well-known evidence-based strategies.

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The MEEK technique: 10-year experience at a tertiary burn centre

Abstract

Extensive full-thickness burns pose a great challenge to the burn surgeon. Lack of autograft donor sites is an important limiting factor to achieving wound closure. To overcome this problem, various methods of treatment have been suggested in the past, including the MEEK technique. This study was carried out at the Bogenhausen Hospital Burn Unit, Munich, Germany from 2006 to 2015. There were a total of 148 skin grafting operations. The modified MEEK technique was performed on 67 patients. Patients included 34 males and 33 females, with an average age of 39·6 years. The mean percentage body surface burned was 65%, and full-thickness injury occurred in 52%. The mean area graft per procedure was 20%. The viability of the graft as assessed between the 7th and 10th day was generally in the range of 60–90%. The average number of operations required was 2·21. The mean length of stay was 27 days. Infection was documented in five patients, and seven deaths occurred. The mean follow-up was 3·2 years. When faced with large surface area burns and limited donor sites, the MEEK technique is a satisfactory method for coverage.

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The CelluTome epidermal graft-harvesting system: a patient-reported outcome measure and cost evaluation study

Abstract

Conventional split skin grafts (SSG) require anaesthesia, specialist equipment and can have high donor site (DS) morbidity. The CelluTome epidermal graft-harvesting device is a novel alternative, providing pain-free epidermal skin grafts (ESG) in the outpatient setting, with projected minimal DS trauma and improved patient satisfaction. This study aimed to compare ESG with SSG by evaluating patient-related outcome measures (PROMs) and the cost implications of both.

Twenty patients answered a graft satisfaction questionnaire that evaluated: donor/graft site noticeability, aesthetic concerns, adverse problems and patient satisfaction. Cost/patient was calculated based on total operative expenses and five clinic follow-ups.

In 100% of the ESG cases, there were no DS noticeability or adverse problems compared to 25% in the SSG group. Complete satisfaction with DS appearance was observed in 100% of the ESG cases (50% SSG). Noticeability, adverse problems and overall satisfaction were significantly better in ESG cases (P < 0.05). Graft site parameters were comparable with similar healing outcomes.

The cost per patient for ESG was £431 and £1489 for SSG, with an annual saving of £126 960 based on 10 grafts/month.

For the right patient, CelluTome provides comparable wound healing, with reduced DS morbidity and higher patient satisfaction.

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Overexpression of microRNA-155 suppresses chemokine expression induced by Interleukin-13 in BEAS-2B human bronchial epithelial cells

Publication date: Available online 3 August 2016
Source:Allergology International
Author(s): Satoshi Matsukura, Yuki Osakabe, Ayaka Sekiguchi, Daisuke Inoue, Yusuke Kakiuchi, Toshitaka Funaki, Yohei Yamazaki, Hiromi Takayasu, Hidetsugu Tateno, Eisuke Kato, Aya Wakabayashi, Makoto Hayashi, Gen Ishii, Fumihiro Yamaguchi, Yutaka Tsuchiya, Keita Kasahara, Hironori Sagara, Fumio Kokubu
BackgroundMicroRNAs are non-coding small RNAs that regulate expression of target genes by binding to 3′ untranslated regions. In this study, we used bronchial epithelial cells to investigate in vitro the role of the microRNA miR-155 in the expression of chemokines associated with airway inflammation. miR-155 has previously been reported to regulate allergic inflammation.MethodsBEAS-2B bronchial epithelial cells were cultured and transfected with mimic or inhibitor oligonucleotides to overexpress or downregulate miR-155, as confirmed by real-time PCR. Cells were then stimulated with tumor necrosis factor-alpha, interleukin-13 (IL-13), and a double stranded RNA that binds Toll-like receptor 3. Expression and secretion of the chemokines CCL5, CCL11, CCL26, CXCL8, and CXCL10 were then quantified by real-time PCR and ELISA, respectively. Phosphorylation of signal transducer and activator of transcription 6 (STAT6), a target of the IL-13 receptor, was analyzed by ELISA.Results: miR-155 overexpression significantly suppressed IL-13-induced secretion of CCL11 and CCL26. These effects were specific, and were not observed for other chemokines, nor in cells with downregulated miR-155. miR-155 overexpression also suppressed CCL11 and CCL26 mRNA, but did not affect expression of the IL-13 receptor or phosphorylation of STAT6.Conclusions: miR-155 specifically inhibits IL-13-induced expression of eosinophilic chemokines CCL11 and CCL26 in bronchial epithelial cells, even though the 3'-untranslated region of these genes do not contain a consensus binding site for miR-155.

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Τετάρτη 3 Αυγούστου 2016

Dietary Nitrate on Salivary Flow for Nasopharyngeal Carcinoma Patients

Condition: Nasopharyngeal Carcinoma
Interventions: Dietary Supplement: Sodium nitrate; Dietary Supplement: sodium chloride
Sponsors: Capital Medical University; Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Beijing Friendship Hospital
Not yet recruiting - verified July 2016

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T Cell Receptor-transduced T Cells Targeting NY-ESO-1 for Treatment of Patients With NY-ESO-1- Expressing Malignancies

Conditions: Bladder Carcinoma; Breast Cancer; Esophagus Carcinoma; Lung Cancer; Melanoma; Multiple Myeloma; Neuroblastoma; Ovarian Cancer; Synovial Sarcoma; Other Metastatic Solid Cancers
Interventions: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Anti-NY ESO-1 TCR-transduced T cells
Sponsors: Shenzhen Second People's Hospital; Shenzhen institute for innovation and translational medicine
Recruiting - verified August 2016

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Interest of the F18-choline as a Second Line of the Tracer for Detection of Parathyroid Adenomas

Condition: Hyperparathyroidism
Intervention: Radiation: F18-choline PET examination
Sponsor: Centre Francois Baclesse
Recruiting - verified August 2016

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MetronomIc CApecitabine and DOcetaxel as Second-line Chemotherapy for Advanced Gastric Cancer

Conditions: Gastric Adenocarcinoma,; Gastroesophageal-junction Adenocarcinoma
Interventions: Drug: capecitabine; Drug: Docetaxel
Sponsor: International Group of Endovascular Oncology
Recruiting - verified August 2016

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Nd:YAG Laser Treatment for Extranasal Telangiectasias: A Retrospective Analysis of 38 Patients with Hereditary Hemorrhagic Telangiectasia and Review of the Literature

Background/Aims: Extranasal telangiectasias are common amongst hereditary hemorrhagic telangiectasia (HHT) patients. Telangiectasias can be found at sites like the external nose, lips, oral cavity and fingers. Although not life threatening, they can be annoying for patients and lead to bleeding in some cases, necessitating treatment. Methods: The data of 38 HHT patients treated for extranasal telangiectasias during a period of 10 years by means of Nd:YAG laser were retrospectively analyzed. Results: The telangiectasias treated affected predominantly the tongue, facial skin and lips. During a minimum follow-up of 3 years, only 7 patients required a revision of surgery. Conclusion: This study shows that Nd:YAG laser constitutes a fast, safe and efficient therapeutic modality for the treatment of extranasal telangiectasias.
ORL 2016;78:245-251

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Assessment of periodontal mechano-nociceptive function in healthy Chinese individuals

Publication date: November 2016
Source:Archives of Oral Biology, Volume 71
Author(s): Ran Liu, Xinyu Gu, Jinglu Zhang, Linfeng Yu, Wenjing Chen, Kelun Wang, Peter Svensson
ObjectiveFew clinical techniques are available for the description of mechano-nociceptive function in human periodontal tissues. The objective of this study was to test a new technique for assessment of periodontal mechano-nociceptive function by direct application of controlled forces to the teeth and quantify site, side and gender differences in healthy individuals.DesignTwenty healthy young adults (ten males and ten females) participated. A handheld pressure algometer was used to assess pressure pain threshold (PPT) on the maxillary and mandibular central incisors, canines and first premolars on the left and the right side from two directions: lateral and vertical. Statistical analysis was performed using analyses of variance (ANOVA) with repeated measures to compare data.ResultsThere were significant gender differences of PPT for both lateral (Plateral=0.007) and vertical (Pvertical=0.001) directions with lower thresholds in females (higher sensitivity) than in males. A significant site effect (Plateral=0.002, Pvertical<0.001) was observed with less sensitivity at the first premolar compared to the anterior teeth. No significant right-to-left side differences (P=0.082) were found for the PPTs. There were significant PPT differences between maxillary and mandibular teeth (Plateral=0.020, Pvertical=0.041,) and significant differences between lateral and vertical direction (P<0.001).ConclusionThe novel application of PPTs directly to the teeth indicated an adequate and practical method with potential value for clinical assessment of painful conditions affecting the periodontal ligament.

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Characterization of a novel mutation in PAX9 gene in a family with non-syndromic dental agenesis

Publication date: November 2016
Source:Archives of Oral Biology, Volume 71
Author(s): Marwa Haddaji Mastouri, Peter De Coster, Aicha Zaghabani, Saoussen Trabelsi, Yosra May, Ali Saad, Paul Coucke, Dorra H'mida Ben Brahim
BackgroundDental agenesis is the most common developmental anomaly in man and may present either as an isolated trait or as part of a syndrome, such as ectodermal dysplasia. Until now, the underlying molecular pathogenic mechanisms responsible for dental agenesis are still largely unknown. Several genetic and molecular studies have demonstrated that at least 300 genes are involved in tooth formation and development, coding for specific transcriptional factors, receptors or growth factors that are expressed at specific developmental stages. Dental agenesis in this respect is believed to result from altered expression of one or more of these factors during initiation and early morphogenesis of the tooth germ, and the first actors identified were MSX1 and PAX9.DesignIn this study, we focalized on a Tunisian family with a non-syndromic autosomal dominant form of tooth agenesis. In order to screen for the eventual genetic cause of dental agenesis in this family we sequenced 4 genes; PAX9, WNT10A, MSX1 and AXIN2 using Sanger sequencing.ResultsDirect Screening analysis of PAX9 gene, revealed a novel mutation p.Asp200Serfs*13. It consists of a duplication of 5 basepairs leading to a codon stop 13 position downstream. This novel mutation was found in all affected family members.ConclusionsIn this report, we present the first genetic study of a Tunisian family with a non-syndromic autosomal dominant form of tooth agenesis, in which we identified in PAX9 gene a novel mutation. It most likely results in nonsense mediated RNA decay and haploinsifficiency that reduce the transactivation capacity of PAX9.

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Total Body Composition in Detection of Nutrition Depletion in Head and Neck Patients

Conditions: Head and Neck Neoplasms; Dual-Energy X-Ray Absorptiometry; Malnutrition
Intervention: Other: Imaging by CT and densitometry
Sponsor: Chang Gung Memorial Hospital
Recruiting - verified July 2016

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Dietary Nitrate on Salivary Flow for Nasopharyngeal Carcinoma Patients

T Cell Receptor-transduced T Cells Targeting NY-ESO-1 for Treatment of Patients With NY-ESO-1- Expressing Malignancies

Interest of the F18-choline as a Second Line of the Tracer for Detection of Parathyroid Adenomas

MetronomIc CApecitabine and DOcetaxel as Second-line Chemotherapy for Advanced Gastric Cancer

Nd:YAG Laser Treatment for Extranasal Telangiectasias: A Retrospective Analysis of 38 Patients with Hereditary Hemorrhagic Telangiectasia and Review of the Literature

Assessment of periodontal mechano-nociceptive function in healthy Chinese individuals

Characterization of a novel mutation in PAX9 gene in a family with non-syndromic dental agenesis

Histologic characterization of regenerated tissues after pulp revascularization of immature dog teeth with apical periodontitis using tri-antibiotic paste and platelet-rich plasma

Publication date: November 2016
Source:Archives of Oral Biology, Volume 71
Author(s): Carlos Stambolsky, Soledad Rodríguez-Benítez, José Luis Gutiérrez-Pérez, Daniel Torres-Lagares, Jenifer Martín-González, Juan José Segura-Egea
IntroductionThis study evaluates histologically the efficacy of 4 revascularization protocols in necrotic-infected immature dog teeth with apical periodontitis (AP).MethodsForty double-rooted immature premolar teeth from 4 female Beagle dogs aged 5 months were used. Four teeth were left untouched as negative controls; the other 36 teeth were infected to develop pulp necrosis and AP. Four teeth were left untreated and assigned to the positive control group. The last 28 teeth were randomly assigned into four experimental groups of 8 teeth, each one treated with a different treatment protocol: A1, sodium hypochlorite (SH)+blood clot (BC); A2, SH+platelet-rich plasma (PRP); B1, SH+modified tri-antibiotic paste (mTAP)+BC; B2, SH+mTAP+PRP. The animals were sacrificed, histologic sections were prepared and three parameters were assessed: (1) presence or absence of new hard tissue on the internal root dentinal walls, (2) presence or absence of continued apical closure, and (3) presence or absence of vital tissue within the canal space.ResultsSignificant differences (p<0.05) between the four experimental groups were evident in the percentage of teeth showing histological apical closure (34.5%) and vital tissue within the canal space (68.8%). Group B2 showed the maximal improvement in the three variables assessed (p<0.05). Group A1 showed the minimum percentages in the three parameters assessed (p<0.05).ConclusionsThese results suggest that an intracanal dressing of mTAP, and the use of PRP as scaffold, improves the success rate of the revascularization procedure.

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Similar biological activity in skin prick test for Oralair® (8.200BAU) and Grazax®(6.200BAU) reinforces effective SLIT dosing level

Abstract

In Europe, allergen extracts are standardized based on skin-prick wheal-size in 20-30 allergic subjects. To understand the biologic activity of clinically effective SLIT, we used this method to determine the biologic activity of solution and tablet Timothy grass pollen (TIM) extracts, compared to an FDA approved extract (Reference) of 10.000BAU/mL.

Blinded, quadruplicate SPTs with concentrate and three serial half-log dilutions, allowed construction of a semi-logarithmic regression line per extract. BAU values were obtained from comparison with Reference.

Extracts and dilutions showed a neat linear dose-response (all: R²>0.98) in 33 rhinitis patients. Relative potencies: Staloral^® 12.000BAU/mL, Soluprick^® 10.300BAU/mL, Oralair^® 8.200BAU, Grazax^® 6.200BAU. Even though all extract concentrates differed in wheal-size (p= 0.01-0.001), Grazax^® producing a 25% smaller wheal-size than Oralair^®, the biological activity of these clinically effective TIM tablets led in the same range (6.200-8.200BAU; 0.92-1.23cm²). SLIT dose-finding studies for other pollens might start with allergen extracts producing 1.1cm² wheal surface.

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Similar biological activity in skin prick test for Oralair® (8.200BAU) and Grazax®(6.200BAU) reinforces effective SLIT dosing level

Abstract

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The role of monocytes in ANCA-associated vasculitides

Publication date: Available online 1 August 2016
Source:Autoimmunity Reviews
Author(s): Francesca Brunini, Theresa H. Page, Maurizio Gallieni, Charles D. Pusey
The anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are a heterogeneous group of diseases causing inflammation in small blood vessels and linked by the presence of circulating ANCA specific for proteinase 3 (PR3) or myeloperoxidase (MPO). These antigens are present both in the cytoplasmic granules and on the surface of neutrophils, and the effect of ANCA on neutrophil biology has been extensively studied. In contrast, less attention has been paid to the role of monocytes in AAV. These cells contain PR3 and MPO in lysosomes and can also express them at the cell surface. Monocytes respond to ANCA by producing pro-inflammatory and chemotactic cytokines, reactive-oxygen-species and by up-regulating CD14. Moreover, soluble and cell surface markers of monocyte activation are raised in AAV patients, suggesting an activated phenotype that may persist even during disease remission. The presence of monocyte-derived macrophages and giant cells within damaged renal and vascular tissue in AAV also attests to their role in pathogenesis. In particular, their presence in the tertiary lymphoid organ-like granulomas of AAV patients may generate an environment predisposed to maintaining autoimmunity. Here we discuss the evidence for a pathogenic role of monocytes in AAV, their role in granuloma formation and tissue damage, and their potential to both direct and maintain autoimmunity. ANCA-activation of monocytes may therefore provide an explanation for the relapsing-remitting course of disease and its links with infections. Monocytes may thus represent a promising target for the treatment of this group of life-threatening diseases.

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Pitfalls in Lupus

Publication date: Available online 1 August 2016
Source:Autoimmunity Reviews
Author(s): M. Schneider
"The objective of Pitfall!™ is to guide Harry through a maze of jungle scenes, jumping over or avoiding many deadly dangers… Harry has three lives in each game". If you exchange Harry's adventures with "Life with SLE", patients have to be guided through the jungle having just one life and the deadly dangers are flares, organ manifestations and e.g. consequences of immunosuppressive medications, especially glucocorticoids. Monitoring and treatment in line with recommendations and guidelines may be supportive to survive the first 3 to 5 levels in most cases, but for higher levels of the reality game creativity is needed and life becomes more risky. The aim of this reflection is to identify common pitfalls and to stimulate further research and collaboration in specific areas of the lupus jungle. Topics like "Hidden Power Unit", "Looks similar …", "Rev Meter for SLE", "Flare Prediction", "Level 2: Eminence Based", "Lupus=Lifelong Immunosuppression? !", "Glucocorticoids", "Antimalarials are Contraindicated", "It is all about immunosuppression", "Prediction of Damage" and "Patient Global Assessment (PGA) versus Physician Global Assessment (PhGA)" are addressed. Raised ideas and thoughts are by no means complete or exclusive, but if taken up they may hopefully lead to another approach in daily care and trials in SLE.

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Humoral and cellular autoimmunity in women with recurrent pregnancy losses and repeated implantation failures; a possible role of vitamin D

Publication date: Available online 1 August 2016
Source:Autoimmunity Reviews
Author(s): Joanne Kwak-Kim, Annie Skariah, Li Wu, Dinorah Salazar, Nayoung Sung, Kuniaki Ota
Women with recurrent pregnancy losses (RPL) and repeated implantation failures (RIF) have auto- and cellular immune abnormalities. Approximately, 20% of women with RPL have autoimmune abnormalities, particularly antiphospholipid antibodies (APA). In addition, these women have a higher prevalence of antinuclear antibody, anti-thyroperoxidase and anti-thyroglobulin antibodies, and other non-organ specific autoantibodies. In women with RPL, presence of autoimmunity is often associated with cellular immune abnormalities, such as increased NK cell levels and Th1/Th2 cell ratios. Vitamin D (VD) plays a major role in regulation of auto- and cellular immune abnormalities. VD deficiency is prevalent in women with RPL, and women with VD deficiency have increased auto- and cellular immune abnormalities as compared with women with normal VD levels. VD has immune regulatory effects on various immune effectors including T, B and NK cells. Potential therapeutic application of VD for RPL and RIF with auto- and cellular immune abnormalities should be explored.

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The viral paradigm in type 1 diabetes: who are the main suspects?

Publication date: Available online 1 August 2016
Source:Autoimmunity Reviews
Author(s): Teresa Rodriguez-Calvo, Somayeh Sabouri, Florence Anquetil, Matthias G. von Herrath
Type 1 diabetes (T1D) is an autoimmune disease characterized by the loss of pancreatic beta cells in the islets of Langerhans. Although genetic predisposition plays an important role in T1D development, studies of identical twins suggest that environmental factors such as viruses and other pathogens may be critical triggers either through direct cytolytic effect and gradual beta cell destruction, or by bystander activation of the immune system. In addition, viruses may circumvent the host immune response and have the capacity to establish chronic lifelong infections. The association of various viral infections with the induction of T1D has been extensively studied at the serological and epidemiological level. However, there is still little evidence from studies of human pancreas to confirm their presence or a causal role in disease pathogenesis. In this review, we identify possible suspects for viral triggers of disease and explain their potential roles in the "viral paradigm" of T1D.

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