Δευτέρα 23 Ιανουαρίου 2017
Unilateral Head Impulses Training in Uncompensated Vestibular Hypofunction
The aim of this paper is to report a case of a young woman with unilateral vestibular chronic failure with a poorly compensated vestibuloocular reflex during rapid head rotation. Additionally, she developed migraine symptoms during the treatment with associated chronic dizzy sensations and blurred vision. Her report of blurred vision only improved after she completed a rehabilitation program using fast head impulse rotations towards the affected side for 5 consecutive days. We discuss why we elected this form of treatment and how this method may be useful for different patients.
http://ift.tt/2klHOUj
Dynamic Risk Estimates of Outcome in Chinese Patients with Well-Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation
Thyroid , Vol. 0, No. 0.
http://ift.tt/2jrkgJw
Pulsatile tinnitus and carotid artery dissection
Carotid artery dissection is an uncommon entity associated with head and neck pain, partial Horner's syndrome, amaurosis fugax, and brain ischemia, which may all occur in isolation or in combination. Herein, we report a rare case of cervical artery dissection in which pulsatile tinnitus was the only reported symptom. A 38-years-old man attended our hospital with a 4-days history of left side pulsatile tinnitus which began after stumbling. He had no other symptom. MRA showed luminal stenosis with pseudo lumen of the internal carotid artery.
http://ift.tt/2kbIyYw
Pulsatile tinnitus and carotid artery dissection
Source:Auris Nasus Larynx
Author(s): Yuya Shimizu, Masato Yagi
Carotid artery dissection is an uncommon entity associated with head and neck pain, partial Horner's syndrome, amaurosis fugax, and brain ischemia, which may all occur in isolation or in combination. Herein, we report a rare case of cervical artery dissection in which pulsatile tinnitus was the only reported symptom. A 38-years-old man attended our hospital with a 4-days history of left side pulsatile tinnitus which began after stumbling. He had no other symptom. MRA showed luminal stenosis with pseudo lumen of the internal carotid artery. The patient was diagnosed with left internal carotid artery dissection and treated with antihypertensive therapy accordingly. After 2 months, the stenosis and tinnitus spontaneously resolved.
http://ift.tt/2jWwahX
Healthcare Usage after Uvulopalatopharyngoplasty – Impact of Analgesic Regimen
1) Analyze differences in healthcare usage between subjects receiving different perioperative analgesic medications after uvulopalatopharyngoplasty (UPPP) surgery. 2) Comment on the impact of perioperative analgesic medication on length of hospital stay and complications after UPPP.
http://ift.tt/2jkjJey
Paradoxical Vocal Fold Motion (PVFM) in Pediatric Otolaryngology
Paradoxical vocal fold motion (PVFM) is a condition in which the vocal cords exhibit inappropriate inspiratory adduction, and it has been poorly studied in the pediatric population.
http://ift.tt/2jrsCkb
Sex differences in asthma in swimmers and tennis players
Elite athletes, independent of sport, have increased risk of developing asthma, but little is known about sex difference among adolescent athletes.
http://ift.tt/2kbuIWd
Allergy entry and deletion in the electronic health record
Between 20% and 35% of the US population has 1 or more medication allergy listed in their electronic health record (EHR).1,2 However, prescribers override more than 90% of allergy alerts intended to protect patients from adverse drug events,3 recognizing that many EHR drug allergies are incorrect and/or inconsequential to patient care. The EHR allergy section contains missing reaction details,4 discrepancies with patient interview,5,6 and data entered by health care professionals with limited drug allergy training and knowledge.
http://ift.tt/2jkhNmw
Two inflammatory phenotypes of nasal polyps and comorbid asthma
Nasal polyps and comorbid asthma (NPCA) is a common united airway disease. However, the inflammatory phenotyes of NPCA are not clear.
http://ift.tt/2kbKjoX
IgE-mediated anaphylactic shock caused by pumpkin seed in an adult
Pumpkin (Cucurbita maxima) is a member of the Cucurbitaceae family.1 Although pumpkin seeds are not a common snack, they do contain large quantities of protein,2 making the idea of incorporating them into various foods attractive. Anaphylaxis has been commonly described in other members of the Cucurbitaceae family and with seeds in general,1 but no cases of anaphylaxis with ingestion of pumpkin seeds in an adult has been described. We describe what we believe is the first reported case of immunoglobulin E (IgE)-mediated anaphylaxis caused by ingestion of pumpkin seeds in an adult.
http://ift.tt/2jknQY5
Adult atopic dermatitis and exposure to air pollutants—a nationwide population-based study
There is a trend toward an increased worldwide prevalence of allergic diseases. It is speculated that industrialization with resultant air pollution plays a role. However, there are sparse epidemiologic data on the relation between air pollution and atopic dermatitis (AD) in adults.
http://ift.tt/2kbDPGz
Techniken zur Rekonstruktion der Keystone Area
Zusammenfassung
Hintergrund
Die stabile Fixierung des Neoseptums und der Dreiecksknorpel am Os nasale mittels Naht ist ein essenzieller Schritt bei der Durchführung einer extrakorporalen Septumkorrektur. Nur durch die sichere Rekonstruktion dieser anatomisch wichtigen Struktur können Unregelmäßigkeiten des Nasenrückens mit Einsattelung oder Inverted-V-Deformierungen verhindert werden. Eine weitere wichtige Indikation ist die Vermeidung einer Verbreiterung des Nasenrückens durch Auseinanderweichen der osteotomierten Nasenbeine.
Zielsetzung
Es erfolgt die Vermittlung der Methodik verschiedener Nahttechniken zur Rekonstruktion der Keystone Area.
Schlussfolgerung
Die Criss-cross-Technik, die TTC-suture („transcutaneous transosseous cerclage suture")-Technik sowie die mTTC-suture („modified transcutaneous transosseous cerclage suture")-Technik sind verlässliche und einfache Techniken zur Erzielung eines reproduzierbaren ästhetischen und funktionellen Ergebnisses.
http://ift.tt/2jiD147
Double-blind placebo-controlled randomized clinical trial of verapamil for chronic rhinosinusitis with nasal polyps
Source:Journal of Allergy and Clinical Immunology
Author(s): Marcel M. Miyake, Angela Nocera, Patricia Levesque, Rong Guo, Christine A. Finn, Jeremy Goldfarb, Stacey Gray, Eric Holbrook, Nicolas Busaba, Jose Eduardo L. Dolci, Benjamin S. Bleier
http://ift.tt/2kbm4Hl
IgG trough levels and progression of pulmonary disease in pediatric and adult CVID patients
Source:Journal of Allergy and Clinical Immunology
Author(s): Willemijn JM. Janssen, Firdaus Mohamed Hoesein, Annick AJM. Van de Ven, Jacobien Maarschalk, Florien van Royen, Pim A. de Jong, Elisabeth AM. Sanders, Joris M. van Montfrans, Pauline M. Ellerbroek
Teaser
Capsule summary: Common variable immunodeficiency patients show silent progression of airway disease which was inversely correlated to IgG trough levels. A randomized controlled study into optimal IgG through levels to prevent pulmonary disease progression is warranted.http://ift.tt/2jk31MI
Defects in Lymphocyte Telomere Homeostasis Contribute to Cellular Immune phenotype in Cartilage-Hair Hypoplasia
Publication date: Available online 23 January 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Geraldine Aubert, Kevin A. Strauss, Peter M. Lansdorp, Nicholas L. Rider
BackgroundMutations in the lncRNA RNase component of the Mitochondrial RNA Processing endoribonuclease (RMRP) give rise to the autosomal recessive condition cartilage-hair hypoplasia (CHH). The CHH disease phenotype has some overlap with dyskeratosis congenita, a well known "telomere disorder". RMRP binds the telomerase reverse transcriptase protein TERT in some cell lines, raising the possibility that RMRP may play a role in telomere biology.ObjectiveWe sought to determine if a telomere phenotype is present in immune cells from individuals with CHH and explore mechanisms underlying these observations.MethodsWe assessed the proliferative capacity and telomere length using flow-FISH (in situ hybridization and flow cytometry) of primary lymphocytes from CHH, carrier relatives and control individuals. The role of telomerase holoenzyme components gene expression and activity were assessed by quantitative PCR and telomere repeat amplification assay (TRAP) from PBMC and enriched lymphocyte cultures.ResultsLymphocyte cultures from CHH individuals display growth defects in vitro, consistent with an immune deficiency cellular phenotype. Here we show that telomere length and telomerase activity are impaired in primary lymphocyte subsets from cartilage-hair hypoplasia patients. Notably, telomerase activity is affected in a gene dose dependent manner when comparing heterozygote RMRP carriers to individuals with CHH. Telomerase deficiency in CHH is not mediated by abnormal telomerase gene transcript levels relative to endogenous genes.ConclusionThese findings suggest that telomere deficiency is implicated in the CHH disease phenotype through an as yet unidentified mechanism.
Graphical abstract
Teaser
Patients with CHH often have lymphopenia and impaired lymphocyte proliferation. These defects appear to result from altered lymphocyte telomere homeostasis and may confer susceptibilities to infection and malignancy for the patient with CHH.http://ift.tt/2kb3Zce
Atopic dermatitis and early childhood caries: Results of the GUSTO study
Publication date: Available online 23 January 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Tosha Ashish Kalhan, Evelyn Xiu Ling Loo, Ashish Chetan Kalhan, Michael S. Kramer, Bindu Karunakaran, Carolina Un Lam, Hugo Van Bever, Lynette Pei-chi Shek, Anne Goh, Yap Seng Chong, Bee Wah Lee, Peter Gluckman, Kenneth Kwek, Seang Mei Saw, Keith Godfrey, Chin-Ying Hsu
http://ift.tt/2kbgnsW
Outcomes of pregnancies after kidney transplantation: lessons learned from CKD. A comparison of transplanted, nontransplanted chronic kidney disease patients and low-risk pregnancies: a multicenter nationwide analysis.
http://ift.tt/2jk1AxH
Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells from GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs.
http://ift.tt/2kaZ3UO
Long-term outcomes of kidney transplantation in patients with high levels of preformed DSA: the Necker high-risk transplant program.
http://ift.tt/2jjTyFb
Interpreting Outcomes in DCDD Liver Transplantation: First Report of the Multi-Center IDOL Consortium.
http://ift.tt/2jjUhG0
Möglichkeiten und Grenzen der europäischen und chinesischen Phytotherapie in der Onkologie
Zusammenfassung
Hintergrund
Arzneipflanzen stellen in der europäischen und chinesischen Medizin die ältesten Heilmittel dar, und ihr Einsatz ist bis in die Antike zurückzuverfolgen. Sowohl in Europa als auch in der traditionellen chinesischen Medizin werden Phytotherapeutika in der Onkologie zunehmend angewandt.
Ergebnisse
Arzneipflanzen stehen in Europa als zugelassene Phytopharmaka, im weiteren Sinne auch als homöopathische und anthroposophische Arzneimittel, Nahrungsergänzungsmittel sowie als Rezepturarzneimittel dem Arzt zur Verfügung. Phytopharmaka können als zugelassene sog. rationale Phytopharmaka oder als traditionelle Arzneimittel auf dem Markt sein. In China gibt es v. a. individuelle Pflanzenmischungen. In der Onkologie stehen derzeit kaum Phytopharmaka mit einer dafür nachgewiesenen Anwendung zur Verfügung. Eine Indikation besteht bei den phytotherapeutischen Mistelpräparaten.
Schlussfolgerung
Gerade auf dem Gebiet der Onkologie ist es wesentlich, primär eine wissenschaftlich gesicherte Phytotherapie anzubieten. Adjuvante Darreichungsformen, wie beispielsweise Phytopharmaka und Arzneitees, können in enger Abstimmung mit dem behandelnden Onkologen angewandt werden, soweit keine Bedenken bestehen, sie nicht schaden, nicht irreführend sind und dadurch keine wichtigen Therapien versäumt werden.
http://ift.tt/2kjjgej
Exogenous IL-33 Restores Dendritic Cell Activation and Maturation in Established Cancer [TUMOR IMMUNOLOGY]
The role of IL-33, particularly in tumor growth and tumor immunity, remains ill-defined. We show that exogenous IL-33 can induce robust antitumor effect through a CD8+ T cell–dependent mechanism. Systemic administration of rIL-33 alone was sufficient to inhibit growth of established tumors in transplant and de novo melanoma tumorigenesis models. Notably, in addition to a direct action on CD8+ T cell expansion and IFN- production, rIL-33 therapy activated myeloid dendritic cells (mDCs) in tumor-bearing mice, restored antitumor T cell activity, and increased Ag cross-presentation within the tumor microenvironment. Furthermore, combination therapy consisting of rIL-33 and agonistic anti-CD40 Abs demonstrated synergistic antitumor activity. Specifically, MyD88, an essential component of the IL-33 signaling pathway, was required for the IL-33–mediated increase in mDC number and upregulation in expression of costimulatory molecules. Importantly, we identified that the IL-33 receptor ST2, MyD88, and STAT1 cooperate to induce costimulatory molecule expression on mDCs in response to rIL-33. Thus, our study revealed a novel IL-33–ST2–MyD88–STAT1 axis that restores mDC activation and maturation in established cancer and, thereby, the magnitude of antitumor immune responses, suggesting a potential use of rIL-33 as a new immunotherapy option to treat established cancer.
http://ift.tt/2klnBJU
The MHC Class II Immunopeptidome of Lymph Nodes in Health and in Chemically Induced Colitis [MUCOSAL IMMUNOLOGY]
We recently described a mass spectrometry–based methodology that enables the confident identification of hundreds of peptides bound to murine MHC class II (MHCII) molecules. In this article, we describe its application to the characterization of MHCII-bound peptides isolated from lymph nodes (LNs) of C57BL/6 mice. More than 1000 peptides could be identified in individual analyses, allowing a direct comparison of the MHCII peptidome in different types of normal LNs or in animals with colitis. The peptide length distribution and consensus sequences in axillary, brachial, inguinal, and mesenteric LNs were virtually identical, and a substantial portion of identified peptides corresponded to proteins found in all LNs. However, skin-specific proteins Sbsn and Dmkn and intestine-specific proteins Dmbt1, Krt19, and Maoa, among others, were exclusively identified in skin-draining and mesenteric LNs, respectively. Differences in peptide-presentation patterns were also observed when comparing healthy mice and mice with dextran sodium sulfate–induced colitis. Peptides derived from a subset of proteins (including IgE, Bank1, chondroitin sulfate synthase 2, Cmip, and Fth1) were exclusively identified in mice with colitis, revealing changes in the peptidome associated with the inflammatory process, as well as activation and clonal expansion of B cells.
http://ift.tt/2iXDSZs
Immune Modifications in Fetal Membranes Overlying the Cervix Precede Parturition in Humans [MUCOSAL IMMUNOLOGY]
In humans, parturition is currently viewed as an intrauterine outbreak of inflammation, accompanied by a massive release of proinflammatory cytokines at the maternal–fetal interface that comprises the maternal decidua, placenta, and fetal membranes. At term, fetal membranes overlying the cervix, the future site of rupture, show altered morphology and are termed the zone of altered morphology (ZAM). These alterations occur in normal fetal membranes during late pregnancy, in preparation for labor. In this study, transcriptome, flow cytometry, electron microscopy, and immunohistochemistry analyses collectively highlight a local shift in gene expression and lymphocyte activation in the ZAM. Just before labor, we show that highly polymorphic HLA-A, -B, and -C determinants of fetal origin are selectively exposed in the ZAM to the maternal immune system. A graft rejection-like program occurs in the ZAM, which involves 1) the activation of cytotoxic decidual NK cells, and 2) the decline of decidual immunotolerant M2-like macrophages. Comparison with a prior cohort of fetal membranes shows that acute inflammation only takes place after these first steps of immune modifications. Our results therefore strongly argue in favor of local immune remodeling at the onset of parturition.
http://ift.tt/2klcCR5
Deletion of Nlrp3 Augments Survival during Polymicrobial Sepsis by Decreasing Autophagy and Enhancing Phagocytosis [INFECTIOUS DISEASE AND HOST RESPONSE]
NLRP3 inflammasome is a critical player in innate immunity. Neutrophil recruitment to tissues and effective neutrophil function are critical innate immune mechanisms for bacterial clearance. However, the role of NLRP3 in neutrophil-dependent bacterial clearance in polymicrobial sepsis is unclear. In this study, we evaluated the role of NLRP3 in polymicrobial sepsis induced by cecal ligation and puncture (CLP). Our results showed protection from death in NLRP3-deficient (Nlrp3–/–) and NLRP3 inhibitor–treated wild-type (C57BL/6) mice. Nlrp3–/– and NLRP3 inhibitor–treated mice displayed lower bacterial load but no impairment in neutrophil recruitment to peritoneum. However, neutrophil depletion abrogated protection from death in Nlrp3–/– mice in response to CLP. Intriguingly, following CLP, Nlrp3–/– peritoneal cells (primarily neutrophils) demonstrate decreased autophagy, augmented phagocytosis, and enhanced scavenger receptor (macrophage receptor with collagenous structure) and mannose-binding leptin expression. These findings enhance our understanding of the critical role of NLRP3 in modulating autophagy and phagocytosis in neutrophils and suggest that therapies should be targeted to modulate autophagy and phagocytosis in neutrophils to control bacterial burden in tissues during CLP-induced polymicrobial sepsis.
http://ift.tt/2kldVPS
Targeting Metabolism as a Novel Therapeutic Approach to Autoimmunity, Inflammation, and Transplantation [BRIEF REVIEWS]
Immune cell activation and differentiation occurs concurrently with metabolic reprogramming. This ensures that activated cells generate the energy and substrates necessary to perform their specified function. Likewise, the metabolic programs among different cells of the immune system vary. By targeting different metabolic pathways, these differences allow for selective regulation of immune responses. Further, the relative susceptibility of cells to a metabolic inhibitor is dictated by their metabolic demands; cellular selectivity is based on demand. Therefore, where differences exist in metabolic pathways between healthy and pathogenic cells, there is opportunity for selective regulation with agents lacking intrinsic specificity. There are now a host of studies demonstrating how inhibitors of metabolism (e.g., glycolysis, glutamine metabolism, and fatty acid oxidation) can regulate immune responses and treat immune-mediated pathogenesis. In this brief review we detail how inhibitors of metabolism can be employed to regulate immune responses in both autoimmunity and transplantation.
http://ift.tt/2iXF537
HTLV-1 Tax-Specific CTL Epitope-Pulsed Dendritic Cell Therapy Reduces Proviral Load in Infected Rats with Immune Tolerance against Tax [IMMUNOTHERAPY AND VACCINES]
Adult T cell leukemia/lymphoma (ATL), a CD4+ T cell malignancy with a poor prognosis, is caused by human T cell leukemia virus type 1 (HTLV-1) infection. High proviral load (PVL) is a risk factor for the progression to ATL. We previously reported that some asymptomatic carriers had severely reduced functions of CTLs against HTLV-1 Tax, the major target Ag. Furthermore, the CTL responses tended to be inversely correlated with PVL, suggesting that weak HTLV-1–specific CTL responses may be involved in the elevation of PVL. Our previous animal studies indicated that oral HTLV-1 infection, the major route of infection, caused persistent infection with higher PVL in rats compared with other routes. In this study, we found that Tax-specific CD8+ T cells were present, but not functional, in orally infected rats as observed in some human asymptomatic carriers. Even in the infected rats with immune unresponsiveness against Tax, Tax-specific CTL epitope–pulsed dendritic cell (DC) therapy reduced the PVL and induced Tax-specific CD8+ T cells capable of proliferating and producing IFN-. Furthermore, we found that monocyte-derived DCs from most infected individuals still had the capacity to stimulate CMV-specific autologous CTLs in vitro, indicating that DC therapy may be applicable to most infected individuals. These data suggest that peptide-pulsed DC immunotherapy will be useful to induce functional HTLV-1–specific CTLs and decrease PVL in infected individuals with high PVL and impaired HTLV-1–specific CTL responses, thereby reducing the risk of the development of ATL.
http://ift.tt/2kllp5u
Control of Circulating IgE by the Vitamin D Receptor In Vivo Involves B Cell Intrinsic and Extrinsic Mechanisms [IMMUNE REGULATION]
Vitamin D deficiency is associated with the development of asthma and allergy. The active form of vitamin D [1,25(OH)2D] regulates B cells in vitro and mice without the vitamin D receptor (VDR knockout [KO]) have high serum IgE. Whole-body VDR KO, T cell–specific VDR (T-VDR) KO, B cell–specific VDR (B-VDR) KO, and vitamin D deficient mice were used to determine the targets of vitamin D in the regulation of IgE in vivo. Vitamin D deficient, VDR KO, and B-VDR KO mice developed hyper-IgE, whereas T-VDR KO mice did not. The data show that IL-10 secretion by B cells and CD1d expression on IL-10 secreting B cells was lower in VDR KO mice. Mesenteric lymph node cultures from VDR KO and B-VDR KO mice secreted higher IgE ex vivo than wild-type (WT) cultures, and the addition of IL-10 eliminated the difference in IgE production between VDR KO and WT cultures. The increase in IgE in VDR KO mice was 2-fold greater than in the B-VDR KO mice, suggesting that VDR deficiency in non-B cells contributes to hyper-IgE in vivo. Antibiotic depletion of the microbiota raised serum IgE 4-fold in both WT and VDR KO mice. The VDR directly and indirectly regulates IgE production in B cells. Through the VDR, vitamin D is an environmental factor that helps to maintain low serum IgE responses.
http://ift.tt/2kl6Qi0
Epigenetic and Transcriptional Regulation of IRAK-M Expression in Macrophages [INNATE IMMUNITY AND INFLAMMATION]
During macrophage activation, expression of IL-1R–associated kinase (IRAK)-M is induced to suppress TLR-mediated responses and is a hallmark of endotoxin tolerance. Endotoxin tolerance requires tight regulation of genes occurring at the transcriptional and epigenetic levels. To identify novel regulators of IRAK-M, we used RAW 264.7 macrophages and performed a targeted RNA interference screen of genes encoding chromatin-modifying enzymes, signaling molecules, and transcription factors involved in macrophage activation. Among these, the transcription factor CCAAT/enhancer binding protein (C/EBP)β, known to be involved in macrophage inactivation, was necessary for the induction of IRAK-M expression. Chromatin immunoprecipitation showed that C/EBPβ was recruited to the IRAK-M promoter following LPS stimulation and was indispensable for IRAK-M transcriptional activation. Among histone 3–modifying enzymes, our screen showed that knockdown of the histone 3 lysine 27 (H3K27) methyltransferase and part of the polycomb recessive complex 2, enhancer of Zeste 2, resulted in IRAK-M overexpression. In contrast, knockdown of the H3K27 demethylase ubiquitously transcribed tetratricopeptide repeat X chromosome suppressed the induction of IRAK-M in response to LPS stimulation. Accordingly, we demonstrated that H3K27 on the IRAK-M promoter is trimethylated in unstimulated cells and that this silencing epigenetic mark is removed upon LPS stimulation. Our data propose a mechanism for IRAK-M transcriptional regulation according to which, in the naive state, polycomb recessive complex 2 repressed the IRAK-M promoter, allowing low levels of expression; following LPS stimulation, the IRAK-M promoter is derepressed, and transcription is induced to allow its expression.
http://ift.tt/2kl6Q1u
Akt Signaling Pathway in Macrophage Activation and M1/M2 Polarization [BRIEF REVIEWS]
Macrophages become activated initiating innate immune responses. Depending on the signals, macrophages obtain an array of activation phenotypes, described by the broad terms of M1 or M2 phenotype. The PI3K/Akt/mTOR pathway mediates signals from multiple receptors including insulin receptors, pathogen-associated molecular pattern receptors, cytokine receptors, adipokine receptors, and hormones. As a result, the Akt pathway converges inflammatory and metabolic signals to regulate macrophage responses modulating their activation phenotype. Akt is a family of three serine-threonine kinases, Akt1, Akt2, and Akt3. Generation of mice lacking individual Akt, PI3K, or mTOR isoforms and utilization of RNA interference technology have revealed that Akt signaling pathway components have distinct and isoform-specific roles in macrophage biology and inflammatory disease regulation, by controlling inflammatory cytokines, miRNAs, and functions including phagocytosis, autophagy, and cell metabolism. Herein, we review the current knowledge on the role of the Akt signaling pathway in macrophages, focusing on M1/M2 polarization and highlighting Akt isoform–specific functions.
http://ift.tt/2klj0HK
Type II NKT Cells and Their Emerging Role in Health and Disease [BRIEF REVIEWS]
NKT cells recognize lipid Ags presented by a class I MHC-like molecule CD1d, a member of the CD1 family. Although most initial studies on NKT cells focused on a subset with semi-invariant TCR termed invariant NKT cells, the majority of CD1d-restricted lipid-reactive human T cells express diverse TCRs and are termed type II NKT cells. These cells constitute a distinct population of circulating and tissue-resident effector T cells with immune-regulatory properties. They react to a growing list of self- as well as non–self-lipid ligands, and share some properties with both invariant NKT and conventional T cells. An emerging body of evidence points to their role in the regulation of immunity to pathogens/tumors and in autoimmune/metabolic disorders. An improved understanding of the biology of these cells and the ability to manipulate their function may be of therapeutic benefit in diverse disease conditions.
http://ift.tt/2iXA3ng
Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets [IMMUNOGENETICS]
The respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cells that work together to maintain steady-state respiration. Owing to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systematically identify these subsets in human airways by developing a schema of isolating large numbers of cells by whole-lung bronchoalveolar lavage. Six subsets of phagocytic APC (HLA-DR+) were consistently observed. Aside from alveolar macrophages, subsets of Langerin+, BDCA1–CD14+, BDCA1+CD14+, BDCA1+CD14–, and BDCA1–CD14– cells were identified. These subsets varied in their ability to internalize Escherichia coli, Staphylococcus aureus, and Bacillus anthracis particles. All subsets were more efficient at internalizing S. aureus and B. anthracis compared with E. coli. Alveolar macrophages and CD14+ cells were overall more efficient at particle internalization compared with the four other populations. Subsets were further separated into two groups based on their inherent capacities to upregulate surface CD83, CD86, and CCR7 expression levels. Whole-genome transcriptional profiling revealed a clade of "true dendritic cells" consisting of Langerin+, BDCA1+CD14+, and BDCA1+CD14– cells. The dendritic cell clade was distinct from a macrophage/monocyte clade, as supported by higher mRNA expression levels of several dendritic cell–associated genes, including CD1, FLT3, CX3CR1, and CCR6. Each clade, and each member of both clades, was discerned by specific upregulated genes, which can serve as markers for future studies in healthy and diseased states.
http://ift.tt/2kliQ3n
Chemorepellent Semaphorin 3E Negatively Regulates Neutrophil Migration In Vitro and In Vivo [ALLERGY AND OTHER HYPERSENSITIVITIES]
Neutrophil migration is an essential step in leukocyte trafficking during inflammatory responses. Semaphorins, originally discovered as axon guidance cues in neural development, have been shown to regulate cell migration beyond the nervous system. However, the potential contribution of semaphorins in the regulation of neutrophil migration is not well understood. This study examines the possible role of a secreted chemorepellent, Semaphorin 3E (Sema3E), in neutrophil migration. In this study, we demonstrated that human neutrophils constitutively express Sema3E high-affinity receptor, PlexinD1. Sema3E displayed a potent ability to inhibit CXCL8/IL-8–induced neutrophil migration as determined using a microfluidic device coupled to real-time microscopy and a transwell system in vitro. The antimigratory effect of Sema3E on human neutrophil migration was associated with suppression of CXCL8/IL-8–mediated Ras-related C3 botulinum toxin substrate 1 GTPase activity and actin polymerization. We further addressed the regulatory role of Sema3E in the regulation of neutrophil migration in vivo. Allergen airway exposure induced higher neutrophil recruitment into the lungs of Sema3e–/– mice compared with wild-type controls. Administration of exogenous recombinant Sema3E markedly reduced allergen-induced neutrophil recruitment into the lungs, which was associated with alleviation of allergic airway inflammation and improvement of lung function. Our data suggest that Sema3E could be considered an essential regulatory mediator involved in modulation of neutrophil migration throughout the course of neutrophilic inflammation.
http://ift.tt/2klmhHb
HIV-1 Latency-Reversing Agents Prostratin and Bryostatin-1 Induce Blood-Brain Barrier Disruption/Inflammation and Modulate Leukocyte Adhesion/Transmigration [INFECTIOUS DISEASE AND HOST RESPONSE]
A shock-and-kill approach involving the simultaneous treatment of HIV-1–infected patients with latency-reversing agents (LRAs) and combination antiretroviral therapy was proposed as a means to eradicate viral reservoirs. Currently available LRAs cannot discriminate between HIV-1–infected and uninfected cells. Therefore, the risks and benefits of using broad-spectrum LRAs need to be carefully evaluated, particularly in the CNS, where inflammation and leukocyte transmigration must be tightly regulated. We used a real-time impedance-sensing system to dynamically record the impact of different classes of LRAs on the integrity of tight monolayers of the immortalized human cerebral microvascular endothelial cell line hCMEC/D3. Results show that prostratin and bryostatin-1 can significantly damage the integrity of an endothelial monolayer. Moreover, prostratin and bryostatin-1 induce secretion of some proinflammatory cytokines and an increase of ICAM-1 expression. Additional studies demonstrated that prostratin and bryostatin-1 also affect adhesion and transmigration of CD4+ and CD8+ T cells as well as monocytes in an in vitro human blood–brain barrier (BBB) model. Prostratin and bryostatin-1 could thus be considered as potent regulators of BBB permeability and inflammation that influence leukocyte transport across the BBB. Altogether, these findings contribute to a better understanding of the potential risks and benefits of using a shock-and-kill approach with LRAs on the normal physiological functions of the BBB.
http://ift.tt/2kldTYg
Allergen Valency, Dose, and Fc{varepsilon}RI Occupancy Set Thresholds for Secretory Responses to Pen a 1 and Motivate Design of Hypoallergens [ALLERGY AND OTHER HYPERSENSITIVITIES]
Ag-mediated crosslinking of IgE–FcRI complexes activates mast cells and basophils, initiating the allergic response. Of 34 donors recruited having self-reported shrimp allergy, only 35% had significant levels of shrimp-specific IgE in serum and measurable basophil secretory responses to rPen a 1 (shrimp tropomyosin). We report that degranulation is linked to the number of FcRI occupied with allergen-specific IgE, as well as the dose and valency of Pen a 1. Using clustered regularly interspaced palindromic repeat–based gene editing, human RBLrαKO cells were created that exclusively express the human FcRIα subunit. Pen a 1–specific IgE was affinity purified from shrimp-positive plasma. Cells primed with a range of Pen a 1–specific IgE and challenged with Pen a 1 showed a bell-shaped dose response for secretion, with optimal Pen a 1 doses of 0.1–10 ng/ml. Mathematical modeling provided estimates of receptor aggregation kinetics based on FcRI occupancy with IgE and allergen dose. Maximal degranulation was elicited when ~2700 IgE–FcRI complexes were occupied with specific IgE and challenged with Pen a 1 (IgE epitope valency of ≥8), although measurable responses were achieved when only a few hundred FcRI were occupied. Prolonged periods of pepsin-mediated Pen a 1 proteolysis, which simulates gastric digestion, were required to diminish secretory responses. Recombinant fragments (60–79 aa), which together span the entire length of tropomyosin, were weak secretagogues. These fragments have reduced dimerization capacity, compete with intact Pen a 1 for binding to IgE–FcRI complexes, and represent a starting point for the design of promising hypoallergens for immunotherapy.
http://ift.tt/2iXDRom
TTLL12 Inhibits the Activation of Cellular Antiviral Signaling through Interaction with VISA/MAVS [INNATE IMMUNITY AND INFLAMMATION]
Upon virus infection, host cells use retinoic-acid–inducible geneI I (RIG-I)–like receptors to recognize viral RNA and activate type I IFN expression. To investigate the role of protein methylation in the antiviral signaling pathway, we screened all the SET domain–containing proteins and identified TTLL12 as a negative regulator of RIG-I signaling. TTLL12 contains SET and TTL domains, which are predicted to have lysine methyltransferase and tubulin tyrosine ligase activities, respectively. Exogenous expression of TTLL12 represses IFN-β expression induced by Sendai virus. TTLL12 deficiency by RNA interference and CRISPR-gRNA techniques increases the induced IFN-β expression and inhibits virus replication in the cell. The global gene expression profiling indicated that TTLL12 specifically inhibits the expression of the downstream genes of innate immunity pathways. Cell fractionation and fluorescent staining indicated that TTLL12 is localized in the cytosol. The mutagenesis study suggested that TTLL12's ability to repress the RIG-I pathway is probably not dependent on protein modifications. Instead, TTLL12 directly interacts with virus-induced signaling adaptor (VISA), TBK1, and IKK, and inhibits the interactions of VISA with other signaling molecules. Taken together, our findings demonstrate TTLL12 as a negative regulator of RNA-virus–induced type I IFN expression by inhibiting the interaction of VISA with other proteins.
http://ift.tt/2klnwWC
Immunodominance of Antibody Recognition of the HIV Envelope V2 Region in Ig-Humanized Mice [ANTIGEN RECOGNITION AND RESPONSES]
In the RV144 gp120 HIV vaccine trial, decreased transmission risk was correlated with Abs that reacted with a linear epitope at a lysine residue at position 169 (K169) in the HIV-1 envelope (Env) V2 region. The K169 V2 response was restricted to Abs bearing V rearrangements that expressed aspartic acid/glutamic acid in CDR L2. The AE.A244 gp120 in AIDSVAX B/E also bound to the unmutated ancestor of a V2-glycan broadly neutralizing Ab, but this Ab type was not induced in the RV144 trial. In this study, we sought to determine whether immunodominance of the V2 linear epitope could be overcome in the absence of human V rearrangements. We immunized IgH- and Ig-humanized mice with the AE.A244 gp120 Env. In these mice, the V2 Ab response was focused on a linear epitope that did not include K169. V2 Abs were isolated that used the same human VH gene segment as an RV144 V2 Ab but paired with a mouse L chain. Structural characterization of one of these V2 Abs revealed how the linear V2 epitope could be engaged, despite the lack of aspartic acid/glutamic acid encoded in the mouse repertoire. Thus, despite the absence of the human V locus in these humanized mice, the dominance of V pairing with human VH for HIV-1 Env V2 recognition resulted in human VH pairing with mouse L chains instead of allowing otherwise subdominant V2-glycan broadly neutralizing Abs to develop.
http://ift.tt/2kljw8L
IL-15 Enables Septic Shock by Maintaining NK Cell Integrity and Function [INNATE IMMUNITY AND INFLAMMATION]
Interleukin 15 is essential for the development and differentiation of NK and memory CD8+ (mCD8+) T cells. Our laboratory previously showed that NK and CD8+ T lymphocytes facilitate the pathobiology of septic shock. However, factors that regulate NK and CD8+ T lymphocyte functions during sepsis are not well characterized. We hypothesized that IL-15 promotes the pathogenesis of sepsis by maintaining NK and mCD8+ T cell integrity. To test our hypothesis, the pathogenesis of sepsis was assessed in IL-15–deficient (IL-15 knockout, KO) mice. IL-15 KO mice showed improved survival, attenuated hypothermia, and less proinflammatory cytokine production during septic shock caused by cecal ligation and puncture or endotoxin-induced shock. Treatment with IL-15 superagonist (IL-15 SA, IL-15/IL-15Rα complex) regenerated NK and mCD8+ T cells and re-established mortality of IL-15 KO mice during septic shock. Preventing NK cell regeneration attenuated the restoration of mortality caused by IL-15 SA. If given immediately prior to septic challenge, IL-15–neutralizing IgG M96 failed to protect against septic shock. However, M96 caused NK cell depletion if given 4 d prior to septic challenge and conferred protection. IL-15 SA treatment amplified endotoxin shock, which was prevented by NK cell or IFN- depletion. IL-15 SA treatment also exacerbated septic shock caused by cecal ligation and puncture when given after the onset of sepsis. In conclusion, endogenous IL-15 does not directly augment the pathogenesis of sepsis but enables the development of septic shock by maintaining NK cell numbers and integrity. Exogenous IL-15 exacerbates the severity of sepsis by activating NK cells and facilitating IFN- production.
http://ift.tt/2klewRD
Key Residues at Third CDR3{beta} Position Impact Structure and Antigen Recognition of Human Invariant NK TCRs [ANTIGEN RECOGNITION AND RESPONSES]
The human invariant NK (iNK) TCR is largely composed of the invariant TCR Vα24-Jα18 chain and semivariant TCR Vβ11 chains with variable CDR3β sequences. The direct role of CDR3β in Ag recognition has been studied extensively. Although it was noted that CDR3β can interact with CDR3α, how this interaction might indirectly influence Ag recognition is not fully elucidated. We observed that the third position of Vβ11 CDR3 can encode an Arg or Ser residue as a result of somatic rearrangement. Clonotypic analysis of the two iNK TCR types with a single amino acid substitution revealed that the staining intensity by anti-Vα24 Abs depends on whether Ser or Arg is encoded. When stained with an anti–Vα24-Jα18 Ab, human primary invariant NKT cells could be divided into Vα24 low- and high-intensity subsets, and Arg-encoding TCR Vβ11 chains were more frequently isolated from the Vα24 low-intensity subpopulation compared with the Vα24 high-intensity subpopulation. The Arg/Ser substitution also influenced Ag recognition as determined by CD1d multimer staining and CD1d-restricted functional responses. Importantly, in silico modeling validated that this Ser-to-Arg mutation could alter the structure of the CDR3β loop, as well as the CDR3α loop. Collectively, these results indicate that the Arg/Ser encoded at the third CDR3β residue can effectively modulate the overall structure of, and Ag recognition by, human iNK TCRs.
http://ift.tt/2iXJ6Ew
Molecular characterization of CD44 + /CD24 − /Ck + /CD45 − cells in benign and malignant breast lesions
Abstract
Breast cancer epithelial cells with the CD44+/CD24−/low phenotype possess tumor-initiating cells and epithelial-mesenchymal transition (EMT) capacity. Massive parallel sequencing can be an interesting approach to deepen the molecular characterization of these cells. We characterized CD44+/CD24−/cytokeratin(Ck)+/CD45− cells isolated through flow cytometry from 43 biopsy and 6 mastectomy samples harboring different benign and malignant breast lesions. The Ion Torrent Ampliseq Cancer Hotspot panel v2 (CHPv2) was used for the identification of somatic mutations in the DNA extracted from isolated CD44+/CD24−/Ck+/CD45− cells. E-Cadherin and vimentin immunohistochemistry was performed on sections from the corresponding formalin-fixed, paraffin-embedded (FFPE) blocks. The percentage of CD44+/CD24−/Ck+/CD45− cells increased significantly from non-malignant to malignant lesions and in association with a significant increase in the expression of vimentin. Non-malignant lesions harbored only a single-nucleotide polymorphism (SNP). Mutations in the tumor suppressor p53 (TP53), NOTCH homolog 1 (NOTCH1), phosphatase and tensin homolog (PTEN), and v-akt murine thymoma viral oncogene homolog 1 (AKT1) genes were found in isolated CD44+/CD24−/Ck+/CD45− cells from ductal carcinomas in situ (DCIS). Additional mutations in the colony-stimulating factor 1 receptor (CSF1R), ret proto-oncogene (RET), and TP53 genes were also identified in invasive ductal carcinomas (IDCs). The use of massive parallel sequencing technology for this type of application revealed to be extremely effective even when using small amounts of DNA extracted from a low number of cells. Additional studies are now required using larger cohorts to design an appropriate mutational profile for this phenotype.
http://ift.tt/2iXIjDM
Dermatophytid
Zusammenfassung
Nach aktueller Definition versteht man unter einem Mykid eine hypererge Reaktionslage, bei der auch fern vom Herd der Infektion Hauterscheinungen auftreten, in denen keine Pilze nachweisbar sind. Als Kriterien für ein Dermatophyten-bedingtes Mykid (Dermatophytid) gelten: 1. nachgewiesene Dermatophytose an einer anderen Lokalisation, 2. kein Nachweis von Pilzelementen in den id-bedingten Effloreszenzen, 3. oft zunächst Verschlechterung unter Therapie mit hochwirksamen systemischen Antimykotika, 4. Abheilung nach Therapie der Dermatophytose. Häufigstes Dermatophytid ist ein symmetrisches dyshidrosiformes Mykid der Hände in Zusammenhang mit einer meist akut inflammatorischen Fußmykose insbesondere durch Trichophyton mentagrophytes. Bei Tinea capitis können Dermatophytide neben dem Lichen trichophyticus eine große klinische Varianz aufweisen und treten nicht selten erst unter der erforderlichen systemischen antimykotischen Therapie auf. Sie müssen von einer Arzneireaktion abgegrenzt werden. Zusätzlich zu einer systemischen antimykotischen Therapie führt, ggf. neben einer kurzfristigen oralen Gabe von Steroiden, die topische Applikation einer Kombination aus einem Antimykotikum mit einem Glukokortikoid zu einem raschen Rückgang von Entzündung und Juckreiz, gerade wenn es nach Einleiten der systemischen antimykotischen Therapie zu einem Aufflammen der Entzündung kommt (Overtreatment-Phänomen).
http://ift.tt/2jV94YZ
Inclusion of BLIMP-1 + effector regulatory T cells improves the Immunoscore in a cohort of New Zealand colorectal cancer patients: a pilot study
Abstract
Analysis of tumour-infiltrating T cells in colorectal cancer can predict disease-free survival. The Immunoscore, obtained by quantifying tumour-infiltrating CD3+ and CD8+ T cells, may improve current staging. Effector regulatory T cells are a potently suppressive subset in mice and, while present in human colorectal cancer, their role in patient outcome is unknown. Immunofluorescence was used to analyse immune cell infiltrates in patients with early (stage II) colorectal cancer with (n = 13) and without (n = 19) recurrent disease. CD3 and CD8 were used for the Immunoscore; FOXP3, BLIMP-1 and CD3 to identify effector regulatory T cells. Patients with high Immunoscores had increased disease-free survival compared to patients with low Immunoscores (Log-rank test p < 0.01). Prediction of outcome was further improved by stratifying patients with a low Immunoscore according to CD3+FOXP3+BLIMP-1+ cell infiltration at the invasive margin. Patients with a low Immunoscore and high infiltrate of CD3+FOXP3+BLIMP-1+ cells tended to have better disease-free survival than patients with low Immunoscore and low infiltrate of CD3+FOXP3+BLIMP-1+ cells. Patients with a high Immunoscore had better disease-free survival than patients with a low Immunoscore and low infiltrate of CD3+ FOXP3+ BLIMP-1+ cells (Log-rank test p < 0.001). These results indicate that tumour infiltration with effector regulatory T cells improves the prognostic value of the Immunoscore and implies that these cells may play a role in colorectal cancer patient outcome.
http://ift.tt/2j4Fc7Y
Randomized trial of a novel double lumen nasopharyngeal catheter versus traditional nasal cannula during total intravenous anesthesia for gastrointestinal procedures
Patients undergoing general anesthesia routinely experience episodes of hypoxemia. There are multiple causes of procedural oxygen desaturation including upper airway obstruction and central hypoventilation. We hypothesize that oxygen supplementation via nasopharyngeal catheter (NPC) will decrease the number of episodes of hypoxemia as compared to traditional NC oxygen supplementation in patients undergoing general anesthesia provided by an anesthesia provider for gastrointestinal endoscopy procedures.
http://ift.tt/2kkXliQ
One lung ventilation with laryngeal mask prosealtm and EZ-blockertm in a partial laryngectomized patient
To the Editor;
http://ift.tt/2iXwOvK
Lymphoepithelial Sialadenitis Involving HIV-Infected and Sjogren Syndrome Patients: A Cytologic Study
Abstract
Lymphoepithelial salivary gland cysts are rarely seen in autoimmune diseases particularly Sjogren syndrome as well as in HIV for which medical management is advocated. To study the morphology of these cysts, correlate with the disease process and assess the final outcome. Case series. Fine needle aspiration clinic. HIV-infected and autoimmune disease patients with lymphoepithelial cysts. Antiretroviral therapy for HIV-patients and anti-inflammatory drugs for Sjogren syndrome. Three HIV-infected patients (two children and one adult) and three middle aged female patients presented with parotid and submandibular cysts, two of which were bilateral along with submandibular (one each in the HIV and the autoimmune group). In the adult HIV-patient, the cyst was found at the inception of the disease while the other pediatric HIV-patients just crossed a decade. Of the other three cases of Sjogren syndrome, two were primary and one, secondary to rheumatoid arthritis. All the cysts regressed completely with treatment of the respective diseases which was confirmed by ultrasonograms. Lymphoepithelial cysts are produced by release of serous secretion by the acinar and ductal cells within the epithelial islands in the process of their destruction. Possibly, antibody mediated increased secretion in the initial stages also plays a role. Lymphoepithelial cysts of HIV patients may occur in the course of treatment, not necessarily in the beginning, though it resolves spontaneously. Lymphoepithelial cysts of primary or secondary Sjogren syndrome may be repressed sufficiently by anti-inflammatory/immunosuppressant treatment.
http://ift.tt/2jIzomD
A randomized controlled trial comparing paravertebral block via the surgical field with thoracic epidural block using ropivacaine for post-thoracotomy pain relief
Abstract
Purpose
We conducted a comparative study to evaluate analgesic efficacy between paravertebral block via the surgical field (PVB-sf), in which the catheter was inserted into the ventral side of the sympathetic trunk in the paravertebral space by a thoracic surgeon under thoracoscopic visualization, and epidural block (Epi) using ropivacaine for post-thoracotomy pain relief.
Methods
Lung cancer patients scheduled for lobectomy via thoracotomy were randomly allocated to receive either PVB-sf or Epi (n = 36 per group). Before thoracotomy closure, 0.375% ropivacaine was administered as a bolus (PVB-sf, 20 mL; Epi, 5 mL), followed by a 300-mL continuous infusion of 0.2% ropivacaine at 5 mL/h. Postoperative pain was assessed using a visual analog scale (VAS) score at various time points, including the primary endpoint of 2 h after ropivacaine bolus injection. Sensory block area, vital signs, serum ropivacaine concentrations, and side effects were also evaluated.
Results
The Epi group showed significantly lower VAS scores and blood pressure and a wider sensory block area than the PVB-sf group at all evaluation time points. While the mean serum ropivacaine concentration in the PVB-sf group was significantly higher than that in the Epi group until 1 h after injection of the ropivacaine bolus, there was no significant difference at any subsequent assessment point. The incidence of side effects was similar between the groups.
Conclusion
The Epi was superior to PVB-sf for the management of post-thoracotomy pain in this patient cohort. The number of dermatomes anaesthetized by Epi was greater than that anaesthetized by PVB-sf. No difference in complication rates was observed between the two groups.
http://ift.tt/2jj3Ipg
Guselkumab Beats Adalimumab for Moderate to Severe Psoriasis
Reuters Health Information
http://ift.tt/2iyEIf1
A new electroneurography as a prognostic tool for marginal mandibular nerve paralysis after parotid gland surgery: A preliminary evaluation
Marginal mandibular nerve paralysis is the most frequent complication of benign parotid tumor surgery and results in cosmetic deformity. The purpose of this study was to develop a new electroneurography method for marginal mandibular nerve paralysis using electroneurography (ENoG) and judge its usefulness for clinical practice.
http://ift.tt/2k9G0ds
Unilateral vocal fold adductor paralysis after tracheal intubation
Vocal fold immobility is a relatively rare complication that can occur after tracheal intubation. Differential diagnoses include a rare clinical entity called unilateral vocal fold adductor paralysis in which only branches entering the thyroarytenoid and lateral cricoarytenoid muscles of the recurrent laryngeal nerve become paralyzed. Computed tomography and laryngeal electromyography are required to distinguish this condition from others such as cricoarytenoid dislocation/subluxation. Here, we describe two patients who developed vocal fold adductor paralysis after intubation.
http://ift.tt/2jj1OVP
Regenerative treatment for tympanic membrane perforation using gelatin sponge with basic fibroblast growth factor
The objective of this study was to evaluate safety and efficacy of regenerative treatment using gelatin sponge with basic fibroblast growth factor (bFGF) in patients with tympanic membrane perforation (TMP).
http://ift.tt/2k9RptK
Comparison of endoscopic transcanal myringoplasty and endoscopic type I tympanoplasty in repairing medium-sized tympanic perforations
The tympanomeatal flap elevation technique has been used in tympanoplasty for decades; however, this procedure has disadvantages. In recent years, endoscopic transcanal myringoplasty (ETM) has been increasingly practiced and has yielded positive results.This study compares the efficacy of ETM and endoscopic type I tympanoplasty (ETT) in repairing medium-sized perforations of the tympanic membrane.
http://ift.tt/2kkzxj9
The association of superior attachment of uncinate process with pneumatization of middle turbinate: a computed tomographic analysis
Abstract
The frontal sinus outflow pathway is complex and can be influenced by the configuration of the uncinate process (UP). The UP can attach superior to the lamina papyracea, skull base, and middle turbinate. The factors associated with superior attachment remain unclear. This study analyzed the relationships between different types of superior UP attachment and characteristics of the surrounding structures including the agger nasi cell, skull base, and middle turbinate. This retrospective study utilized computed tomography images of 836 sides with identifiable sinus structure from 434 Taiwanese patients. Types of superior UP attachment, height of the ethmoid cribriform plate, prevalence of agger nasi cell, and degree of pneumatization of the middle turbinate were analyzed. In the current study, neither the presence of an agger nasi cell nor height of the cribriform plate had significant relationship with superior UP attachment type. However, UP attachment type was statistically significantly associated with pneumatized middle turbinate (PMT) type (p < 0.01). The PMT group had a higher incidence of UP attachment to the middle turbinate (38%) than the non-PMT group (18%). In the extensive PMT group, the incidence of UP attachment to the middle turbinate was high to 49%. In conclusion, superior UP attachment to the middle turbinate was associated with pneumatization of the middle turbinate. The UP has a greater tendency to attach to the middle turbinate in cases with more PMT.
http://ift.tt/2jiKpfZ
Antibiofilm effects of topical corticosteroids and intranasal saline in patients with chronic rhinosinusitis with nasal polyps depend on bacterial species and their biofilm-forming capacity
Abstract
Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). Intranasal application of corticosteroids and saline is a reliable option for their management. The aim of our study was to evaluate in vitro antibiofilm effects of corticosteroids and isotonic and hypertonic nasal saline in CRSwNP patients. The sinus mucosal specimens were harvested from the ethmoid cavity of 48 patients with CRSwNP and further subjected to hematoxylin–eosin staining and microbiology analysis. The biofilm-forming capacity of isolated bacterial strains was detected by microtiter-plate method and the effects of therapeutic doses of mometasone, fluticasone, isotonic and hypertonic saline on biofilm production were investigated. Bacterial strains were isolated in 42 (87.5%) patients: one organism in 34 (80.9%) and two organisms in 8 (19.1%). Staphylococcus epidermidis (34%) and Staphylococcus aureus (28%) were the most prevalent bacteria in biofilms of CRSwNP patients. Corticosteroids and saline solutions significantly reduced biofilm formation (p < 0.01 and p < 0.05, respectively) with better efficacy of fluticasone and isotonic nasal saline. Treatment with fluticasone, mometasone, isotonic and hypertonic nasal saline completely prevented biofilm production in 66, 50, 84 and 38% of bacterial strains, respectively. The most significant density reduction was observed in biofilm formed by Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae compared to other bacterial species (p < 0.01, p < 0.05, p < 0.05, respectively). The antibiofilm effects of corticosteroids and saline solutions also greatly depended on bacterial biomass (p < 0.05), with the most significant effect on high compared to small amount of formed biofilm. The topical steroids and nasal saline are shown to be potent antibiofilm agents in patients with CRSwNP. The effects of tested compounds depend on bacterial species and volume of formed biofilm.
http://ift.tt/2jpQcOj
Characterizing mandibular growth using three-dimensional imaging techniques and anatomic landmarks
Source:Archives of Oral Biology
Author(s): Michael P. Kelly, Houri K. Vorperian, Yuan Wang, Katelyn K. Tillman, Helen M. Werner, Moo K. Chung, Lindell R. Gentry
ObjectiveTo provide quantitative data on the multi-planar growth of the mandible, this study derived accurate linear and angular mandible measurements using landmarks on three dimensional (3D) mandible models. This novel method was used to quantify 3D mandibular growth and characterize the emergence of sexual dimorphism.DesignCross-sectional and longitudinal imaging data were obtained from a retrospective computed tomography (CT) database for 51 typically developing individuals between the ages of one and nineteen years. The software Analyze was used to generate 104 3DCT mandible models. Eleven landmarks placed on the models defined six linear measurements (lateral condyle, gonion, and endomolare width, ramus and mental depth, and mandible length) and three angular measurements (gonion, gnathion, and lingual). A fourth degree polynomial fit quantified growth trends, its derivative quantified growth rates, and a composite growth model determined growth types (neural/cranial and somatic/skeletal). Sex differences were assessed in four age cohorts, each spanning five years, to determine the ontogenetic pattern producing sexual dimorphism of the adult mandible.ResultsMandibular growth trends and growth rates were non-uniform. In general, structures in the horizontal plane displayed predominantly neural/cranial growth types, whereas structures in the vertical plane had somatic/skeletal growth types. Significant prepubertal sex differences in the inferior aspect of the mandible dissipated when growth in males began to outpace that of females at eight to ten years of age, but sexual dimorphism re-emerged during and after puberty.ConclusionsThis 3D analysis of mandibular growth provides preliminary normative developmental data for clinical assessment and craniofacial growth studies.
http://ift.tt/2jR0U3u
Characterizing mandibular growth using three-dimensional imaging techniques and anatomic landmarks
Source:Archives of Oral Biology
Author(s): Michael P. Kelly, Houri K. Vorperian, Yuan Wang, Katelyn K. Tillman, Helen M. Werner, Moo K. Chung, Lindell R. Gentry
ObjectiveTo provide quantitative data on the multi-planar growth of the mandible, this study derived accurate linear and angular mandible measurements using landmarks on three dimensional (3D) mandible models. This novel method was used to quantify 3D mandibular growth and characterize the emergence of sexual dimorphism.DesignCross-sectional and longitudinal imaging data were obtained from a retrospective computed tomography (CT) database for 51 typically developing individuals between the ages of one and nineteen years. The software Analyze was used to generate 104 3DCT mandible models. Eleven landmarks placed on the models defined six linear measurements (lateral condyle, gonion, and endomolare width, ramus and mental depth, and mandible length) and three angular measurements (gonion, gnathion, and lingual). A fourth degree polynomial fit quantified growth trends, its derivative quantified growth rates, and a composite growth model determined growth types (neural/cranial and somatic/skeletal). Sex differences were assessed in four age cohorts, each spanning five years, to determine the ontogenetic pattern producing sexual dimorphism of the adult mandible.ResultsMandibular growth trends and growth rates were non-uniform. In general, structures in the horizontal plane displayed predominantly neural/cranial growth types, whereas structures in the vertical plane had somatic/skeletal growth types. Significant prepubertal sex differences in the inferior aspect of the mandible dissipated when growth in males began to outpace that of females at eight to ten years of age, but sexual dimorphism re-emerged during and after puberty.ConclusionsThis 3D analysis of mandibular growth provides preliminary normative developmental data for clinical assessment and craniofacial growth studies.
http://ift.tt/2jR0U3u
In hepatic venous outflow obstruction, alcoholic liver disease, and nonalcoholic fatty liver disease, centrilobular scars, CD34+ vessels, and keratin 7+ hepatocytes are in close proximity
Abstract
For hepatic venous outflow obstruction, alcoholic liver injury, and nonalcoholic fatty liver disease, the term "centrizonal injury disease" (CID) is used, because injury patterns in all three entities are similar. To elucidate CID-related CD34+ vessels (sinusoids and/or microvessels) and keratin 7+ hepatocytes (K7+ Hs), we examined a series of 41 liver tissue specimens obtained at autopsy and surgery, consisting of 32 CID cases and 9 controls. Centrizonal scars were found in 21 CID cases, and these were associated with centrizonal CD34+ vessels (P = 0.009) and centrizonal K7+ Hs (P < 0.001). Centrizonal coexistence of CD34+ vessels and K7+ Hs was observed in 22 CID cases (P = 0.057). These findings suggest close centrizonal proximity of scar, CD34+ vessels, and K7+ Hs in CID. However, centrizonal K7+ Hs without CD34+ vessels were observed in 21 CID cases. CD34+ vessels were detectable in all control samples and may represent the normal vascular bed. In 29 CID cases, centrizonal CD34+ vessel density was higher than that in controls. However, most appeared to be continuous with periportal and/or interlobular CD34+ vessels, and those CD34+ vessels restricted to centrizonal regions were focal and limited in seven CID cases. Centrizonal CD34+ vessels were associated with venoportal adhesions (P = 0.027). Our findings suggest that CID induces both venoportal adhesion-related structural distortion and expansion of normally present CD34+ vessels, which may result in increased centrizonal CD34+ vessel density.
http://ift.tt/2j5MbNU
Prospective Study for Prognostic Biomarkers of Nasopharyngeal Carcinoma
Condition: Nasopharyngeal Carcinoma
Intervention: Other: laboratory biomarker analysis
Sponsors: Sun Yat-sen University; Guilin Medical University, China
Not yet recruiting - verified January 2017
http://ift.tt/2jU84UV
Intervention: Other: laboratory biomarker analysis
Sponsors: Sun Yat-sen University; Guilin Medical University, China
Not yet recruiting - verified January 2017
http://ift.tt/2jU84UV
Treatment of Primary Hyperparathyroidism With Denosumab and Cinacalcet.
Conditions: Primary Hyperparathyroidism; Parathyroid Adenoma; Parathyroid Hyperplasia
Interventions: Drug: Cinacalcet 30 mg Tablet; Drug: Denosumab Inj 60 mg/ml; Other: Placebo tablets; Other: Saline Injection (Placebo)
Sponsors: Peter Vestergaard; Aalborg University
Not yet recruiting - verified January 2017
http://ift.tt/2j5LtQK
Interventions: Drug: Cinacalcet 30 mg Tablet; Drug: Denosumab Inj 60 mg/ml; Other: Placebo tablets; Other: Saline Injection (Placebo)
Sponsors: Peter Vestergaard; Aalborg University
Not yet recruiting - verified January 2017
http://ift.tt/2j5LtQK
Radiation Plus Concurrent Nimotuzumab in Elderly Patients With Locoregionally Advanced Nasopharyngeal Carcinoma
Condition: Nasopharyngeal Carcinoma
Interventions: Drug: Nimotuzumab; Radiation: Radiation
Sponsor: Zhejiang Cancer Hospital
Recruiting - verified January 2017
http://ift.tt/2jTZOED
Interventions: Drug: Nimotuzumab; Radiation: Radiation
Sponsor: Zhejiang Cancer Hospital
Recruiting - verified January 2017
http://ift.tt/2jTZOED
MRI Screening of Second Primary Cancer Occurring Within Radiation Fields After Treatment by External Beam Radiation Therapy for Hereditary Retinoblastoma (DepiSCARRH)
Condition: Hereditary Retinoblastoma
Intervention: Procedure: MRI
Sponsor: Institut Curie
Not yet recruiting - verified January 2017
http://ift.tt/2j5GQpW
Intervention: Procedure: MRI
Sponsor: Institut Curie
Not yet recruiting - verified January 2017
http://ift.tt/2j5GQpW
WEE1 Inhibitor With Cisplatin and Radiotherapy: A Trial in Head and Neck Cancer
Conditions: Hypopharynx Squamous Cell Carcinoma; Oral Cavity Squamous Cell Carcinoma; Larynx Cancer
Interventions: Drug: AZD1775; Drug: Cisplatin; Radiation: Radiotherapy
Sponsors: University of Birmingham; AstraZeneca; Cancer Research UK
Not yet recruiting - verified January 2017
http://ift.tt/2jTSrNc
Interventions: Drug: AZD1775; Drug: Cisplatin; Radiation: Radiotherapy
Sponsors: University of Birmingham; AstraZeneca; Cancer Research UK
Not yet recruiting - verified January 2017
http://ift.tt/2jTSrNc
Oral Combination Vaccine, Comprising Bifidobacterium Displaying Hepatitis C Virus Nonstructural Protein 3 and Interferon-α, Induces Strong Cellular Immunity Specific to Nonstructural Protein 3 in Mice
Viral Immunology , Vol. 0, No. 0.
http://ift.tt/2j5J5K6
Efficacy and relapse-suppression of severe plaque psoriasis by oxymatrine: Results from a single blinded randomized controlled clinical trial
Abstract
Background
Current drugs in psoriasis treatment are associated with drawbacks such as rapid recrudescence, high costs and unwanted side effects. Oxymatrine has a long clinical use in the treatment of hepatitis and cancer in China.
Objective
To explore the efficacy and safety of oxymatrine injection in patients with severe plaque psoriasis.
Methods
Sixty-seven patients were randomly allocated to receive oxymatrine injections (0.6 g/d, 8weeks) or acitretin capsules (0.75mg/kg·d from week 0~2 and 20-30 mg/d from week 3~8), and followed up for another 24 weeks. The primary end point was the percentage of patients with ≥50% reduction of psoriasis area and severity index (PASI 50) at week 32. The secondary end points included the skin classification grade and the dermatology life quality index (DLQI). Side effects during the whole study were recorded to assess the safety profile.
Results
Treatment with oxymatrine or acitretin for 8 weeks significantly decreased PASI score, skin classification grade and DLQI score (P<0.001), with no significant differences between oxymatrine and acitretin groups in terms of PASI 50. However, at week 32, the relapse rate in oxymatrine group were significantly lower than that of acitretin group (P<0.001). Moreover, while the number of patients with metabolic abnormalities was increased in the acitretin group, a significant reduction was observed in the oxymatrine group. In addition, rates of adverse reactions were significantly decreased in the oxymatrine group as compared to that of acitretin group (P<0.001).
Conclusion
Treatment with oxymatrine effectively ameliorated the severe plaque psoriasis, and was accompanied by only minor adverse effects.
This article is protected by copyright. All rights reserved.
http://ift.tt/2jJpn8W
Atenolol Treatment for Infantile Haemangioma
Abstract
Since 2008, propranolol has become the first line recommended treatment for infantile haemangiomas (IH) 1,2. Propranolol is a synthetic beta-adrenergic receptor-blocking agent that is non-selective because it blocks both beta 1 and beta 2 adrenergic receptors 3,4. The most commonly reported side effects in infants treated with propranolol for IH are sleep disturbance, cool mottled peripheries and bronchial hyperactivity 3,5 and concerns have been raised about the potential long-term neurodevelopmental or cognitive effects6, 7. A proportion of patients has to stop treatment because of adverse effects, thus treatments with other beta-blockers are considered.
This article is protected by copyright. All rights reserved.
http://ift.tt/2jTGZkN
Comparison of the paper-based and electronic versions of the Dermatology Life Quality Index (DLQI): evidence of equivalence
Abstract
Background
The use of patient-reported outcome measures in electronic format has been increasing. However, these formats are usually not validated or compared to the original paper-based formats, so there is no evidence that they are completed in the same way.
Objectives
The aim of this study was to compare the conventional paper version and a web-based application version (iPad®) of the DLQI to assess equivalence of scores.
Methods
The study employed a randomized cross-over design using a within-subjects comparison of the two formats of the questionnaire. International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines were followed. Subjects aged over 18 years with any confirmed skin condition were recruited from a teaching hospital dermatology outpatient clinic. Expected Intra-class correlation coefficient (ICC) was 0.9 (α = 0.05)
Results
A total of 104 patients were recruited, median age=53.5 years (IQR=37.3-67.8, 43% male). The Intraclass correlation coefficient (ICC) showed high concordance between the total DLQI scores from paper and iPad® versions (ICC = 0.98; 95% CI 0.97-0.99). Patients took a median of 78 seconds to complete the electronic version and 73 seconds for paper (p=0.008): 76% preferred the electronic version and perceived completion to take a shorter time.
Conclusions
There is high concordance, and thus equivalence, between the iPad and paper versions of the DLQI, with an ICC of 0.98, and a clear patient preference for the iPad version.
This article is protected by copyright. All rights reserved.
http://ift.tt/2jJkCfi
Deficient stratum corneum intercellular lipid in a Japanese patient with lamellar ichthyosis by a homozygous deletion mutation in SDR9C7
Abstract
Autosomal recessive congenital ichthyosis (ARCI) is an umbrella term for inherited non-syndromic ichthyosis, which includes harlequin ichthyosis, lamellar ichthyosis (LI), congenital ichthyosiform erythroderma and pleomorphic ichthyosis (also called self-healing/self-improving collodion baby).1 The clinical diversity is matched by genetic heterogeneity, with 11 genes currently implicated in the pathobiology of ARCI,2,3 including the most recent discovery of two missense mutations in SDR9C7 in three consanguineous Lebanese families.4 Here, we describe a case of ARCI (LI phenotype) that has a previously unreported homozygous deletion mutation in SDR9C7. We extend the spectrum of clinical features associated with SDR9C7 mutations, and identify deficient intercellular lipid and malformation of intercellular lipid layers in the stratum corneum.
This article is protected by copyright. All rights reserved.
http://ift.tt/2jTBTVS
PIIINP measurements for the detection of liver fibrosis in methotrexate treated psoriasis patients: Daily practice use and clinical implications
Abstract
In the past, a varying incidence of liver fibrosis, which was attributed to methotrexate (MTX) treatment for psoriasis, has been reported.1-5 However, recent reports show lower incidences of liver fibrosis in this group, and a low or absent risk attributable to MTX.6,7 Dawwas et al. found that end-stage liver disease related to MTX was very uncommon (0.07% of 158 904 liver transplant patients), and that features of the metabolic syndrome were prevalent in those affected.6
This article is protected by copyright. All rights reserved.
http://ift.tt/2jJtrG6
Frontal fibrosing alopecia in men – an association with facial moisturisers and sunscreens
Abstract
Frontal fibrosing alopecia (FFA) was first described by Kossard in 1994 in 6 postmenopausal women.1 FFA remained rare during the 1990s but in the last 10-15 years it has become increasingly common, a phenomenon observed worldwide. The recent onset and apparent rising incidence of FFA suggest involvement of an environmental factor(s) in the aetiology. We previously reported a questionnaire study in women with FFA that asked about a wide range of medical, social and environmental exposures.
This article is protected by copyright. All rights reserved.
http://ift.tt/2jTD5bQ
Efficacy and comparison of antimalarials in cutaneous lupus erythematosus subtypes: a systematic review and meta-analysis
Summary
Background
The antimalarials (AMs) hydroxychloroquine (HCQ) or chloroquine (CQ) have demonstrated variable cutaneous response rates in Cutaneous Lupus Erythematosus (CLE). Objectives: We sought to assess the global cutaneous response rate to HCQ and CQ, with respect to CLE subtypes, based on previously published studies.
Methods
We performed a systematic review and meta-analysis of studies published in MEDLINE, Embase, Cochrane library between 1965 and December 2015. The proportions of responders to AMs according to CLE subtypes were extracted from individual studies and pooled using random-effects or fixed models. The odds ratio (OR) was used as the measure of association to compare the response rates between CLE subtypes and AMs agents.
Results
Among 1990 lines of treatment with AMs from 31 included studies, the overall response rate to AMs was 63% (95% CI: 55-70) with important statistical heterogeneity across included studies. HCQ had a higher overall efficacy than CQ but this was non-significant (OR: 1.48 [95%CI: 0.98-2.23]). The response rate to AMs was different between CLE subtypes ranging from 31% (95% CI: 20-44) for chilblain lupus to 91% (95% CI: 87-93) for acute CLE and was significantly higher for acute CLE than for subacute CLE and intermittent CLE. In case of failure of a monotherapy with AM, the combinations of Quinacrine with HCQ or CQ seemed effective whereas too little data were available to assess the efficacy of the switch to another AM agent.
Conclusions
Wide discrepancies in cutaneous response to AMs are observed between CLE subtypes. A specific therapeutic approach considering CLE subtypes may improve CLE management.
This article is protected by copyright. All rights reserved.
http://ift.tt/2jJtr94
Histological diagnosis of basal cell carcinoma is not associated with life expectancy in elderly Dutch people; a population-based cohort study
Abstract
Determining appropriate care at the end of life is challenging and has primarily focused on life threatening diseases. Recently, Linos et al highlighted issues about the management of common, nonfatal conditions such as basal cell carcinoma (BCC) in people with limited life expectancy (LLE).1 A prospective cohort study showed that age older than 85 years or the presence of multiple comorbidities did not influence treatment.2 In two controversial position papers they argued that potential overdiagnosis of an asymptomatic slow growing BCC may do more harm than good, advocating a patient-centred care model.
This article is protected by copyright. All rights reserved.
http://ift.tt/2jTHBXS
Concurrent pityriasis rosea and Bell's palsy
Pityriasis rosea is a dermatological disease with a well-documented clinical appearance, but less is known about causes and treatment. Bell's palsy is a neurological condition leading to acute idiopathic hemifacial paralysis. Recent studies indicate that human herpesvirus (HHV) 6–7 reactivation may be a contributing factor to both conditions. We report a case of the 2 concurrent diagnoses that supports a common contributing factor and suggests further awareness and research into the role HHV 6–7 may play in the aetiology of both conditions.
http://ift.tt/2jJmcOt
Surgical resection of a rare cutaneous manifestation of Scedosporium apiospermum in a patient who underwent renal transplant
A man aged 47 years who was immunosuppressed following renal transplantation for focal segmental glomerulosclerosis was referred to the Plastic Surgery team for management of a painful, chronic, granulomatous lesion of the right forearm. Serial ultrasound scans and MRI scans were not diagnostic, but microbiological specimens tested positive for the fungus Scedosporium apiospermum. The renal transplant graft—which was failing—was removed, allowing him to cease immunosuppression. He then underwent a resection of the lesion and reconstruction with a split thickness skin graft. Analysis of the specimen revealed fibrosis, granulomatosis and a collection of S. apiospermum. He was started on voriconazole which, in conjunction with his surgical resection, appears to have kept the disease at bay. With increasing numbers of solid organ transplants and improved survival, this case highlights the growing burden of rare, opportunistic infections, the difficulty in diagnosis and the need for specialist intervention.
http://ift.tt/2jTLVWX
Deceiving proteins! A case of lymphoma and high creatinine
Estimation of kidney function by measuring serum creatinine is one the commonest laboratory tests conducted in clinical practice. Enzymatic methods are often used to measure serum creatinine. Clinicians should be aware of the limitations of these methods, such as test interference with paraproteins.We present a case of falsely elevated serum creatinine in a patient referred for renal biopsy. The combination of fluctuating creatinine and normal blood urea level was unusual. Serum protein electrophoresis revealed the presence of an IgM paraprotein. Further investigations confirmed an underlying diagnosis of lymphoplasmacytoid lymphoma. This case highlights how IgM paraprotein can interfere with creatinine estimation by enzymatic assay and the utility of alternative methods of estimating serum creatinine.
http://ift.tt/2jJmcxX
Residual terminal bowel fistulating into the alimentary tract: a hitherto unreported complication of surgery for anorectal malformation
The residual terminal bowel after pull-through surgery for anorectal malformation has been reported to cause urinary complications. We report two boys where residual bowel has fistulated postoperatively into the alimentary tract causing metabolic and septic complication in one and a large pelvic mass with urinary and rectal obstruction in the other.
http://ift.tt/2jTLxI1
Unilateral interstitial lung disease in a woman aged 35 years
Description
A woman aged 35 years presented to the respiratory services with a history of asthma and recurrent lower respiratory tract infections. Chest X-ray (figure 1) showed mediastinal shift, volume reduction and increased interstitial markings throughout the right lung. Pulmonary function testing revealed a mixed obstructive and restrictive pattern.
Figure1
Chest X-ray.
CT scan demonstrated the absence of the right main pulmonary artery (figure 2). Collateral supply to the right lung was provided from the enlarged right internal mammary and inferior phrenic arteries (figure 3). Fine reticular peripheral interstitial markings, focal areas of ground glass and bronchiolitis were seen in the right lung (figure 4).
Figure 2
CT thorax showing the absence of the right pulmonary artery.
Figure 3
CT showing enlarged inferior phrenic artery.
...http://ift.tt/2jJlKQp
Surgical reconstruction of traumatic ciliary body dialysis: a case report
A cyclodialysis cleft is a gap resulting from disruption of the longitudinal fibers constituting the ciliary body attachment to the scleral spur. The cyclodialysis cleft can be of traumatic or iatrogenic origi...
http://ift.tt/2k8lKZI
Adoptive T Cell Immunotherapy for Patients with Primary Immunodeficiency Disorders
Abstract
Primary immunodeficiency disorders (PID) are a group of inborn errors of immunity with a broad range of clinical severity but often associated with recurrent and serious infections. While hematopoietic stem cell transplantation (HSCT) can be curative for some forms of PID, chronic and/or refractory viral infections remain a cause of morbidity and mortality both before and after HSCT. Although antiviral pharmacologic agents exist for many viral pathogens, these are associated with significant costs and toxicities and may not be effective for increasingly drug-resistant pathogens. Thus, the emergence of adoptive immunotherapy with virus-specific T lymphocytes (VSTs) is an attractive option for addressing the underlying impaired T cell immunity in many PID patients. VSTs have been utilized for PID patients following HSCT in many prior phase I trials, and may potentially be beneficial before HSCT in patients with chronic viral infections. We review the various methods of generating VSTs, clinical experience using VSTs for PID patients, and current limitations as well as potential ways to broaden the clinical applicability of adoptive immunotherapy for PID patients.
http://ift.tt/2jT9WNJ
Adoptive T Cell Immunotherapy for Patients with Primary Immunodeficiency Disorders
Abstract
Primary immunodeficiency disorders (PID) are a group of inborn errors of immunity with a broad range of clinical severity but often associated with recurrent and serious infections. While hematopoietic stem cell transplantation (HSCT) can be curative for some forms of PID, chronic and/or refractory viral infections remain a cause of morbidity and mortality both before and after HSCT. Although antiviral pharmacologic agents exist for many viral pathogens, these are associated with significant costs and toxicities and may not be effective for increasingly drug-resistant pathogens. Thus, the emergence of adoptive immunotherapy with virus-specific T lymphocytes (VSTs) is an attractive option for addressing the underlying impaired T cell immunity in many PID patients. VSTs have been utilized for PID patients following HSCT in many prior phase I trials, and may potentially be beneficial before HSCT in patients with chronic viral infections. We review the various methods of generating VSTs, clinical experience using VSTs for PID patients, and current limitations as well as potential ways to broaden the clinical applicability of adoptive immunotherapy for PID patients.
http://ift.tt/2jT9WNJ
Lymphoepithelial Sialadenitis Involving HIV-Infected and Sjogren Syndrome Patients: A Cytologic Study
Abstract
Lymphoepithelial salivary gland cysts are rarely seen in autoimmune diseases particularly Sjogren syndrome as well as in HIV for which medical management is advocated. To study the morphology of these cysts, correlate with the disease process and assess the final outcome. Case series. Fine needle aspiration clinic. HIV-infected and autoimmune disease patients with lymphoepithelial cysts. Antiretroviral therapy for HIV-patients and anti-inflammatory drugs for Sjogren syndrome. Three HIV-infected patients (two children and one adult) and three middle aged female patients presented with parotid and submandibular cysts, two of which were bilateral along with submandibular (one each in the HIV and the autoimmune group). In the adult HIV-patient, the cyst was found at the inception of the disease while the other pediatric HIV-patients just crossed a decade. Of the other three cases of Sjogren syndrome, two were primary and one, secondary to rheumatoid arthritis. All the cysts regressed completely with treatment of the respective diseases which was confirmed by ultrasonograms. Lymphoepithelial cysts are produced by release of serous secretion by the acinar and ductal cells within the epithelial islands in the process of their destruction. Possibly, antibody mediated increased secretion in the initial stages also plays a role. Lymphoepithelial cysts of HIV patients may occur in the course of treatment, not necessarily in the beginning, though it resolves spontaneously. Lymphoepithelial cysts of primary or secondary Sjogren syndrome may be repressed sufficiently by anti-inflammatory/immunosuppressant treatment.
http://ift.tt/2jIzomD
Postoperative imaging of the internal auditory canal
Abstract
Background
Assessment of the internal auditory canal (IAC) and cochlea is of central importance in neurotology. The artefacts and visibility of active auditory implants on magnetic resonance imaging (MRI) vary because of their specific magnetic components. Knowledge of the size of MRI artefacts and the options for handling them is important for the auditory rehabilitation of specific diseases (e. g., vestibular schwannoma).
Methods
The current article is a literature review.
Results
MRI assessment of the IAC and cochlea after surgical placement of an active auditory implant is feasible only with a percutaneous bone-anchored hearing aid (BAHA, Ponto). When specific factors (implant position and MRI sequence) are taken into consideration, these structures can be visualized even after cochlear implantation. Complications such as magnet dislocation and pain may occur.
Conclusion
The possibility of assessing the IAC and cochlea by MRI is an important aspect that needs to be taken into consideration when planning the auditory rehabilitation of patients after acoustic neuroma surgery.
http://ift.tt/2iUTZXP
Medikamentös induzierte Schlafendoskopie – quo vadis?
Zusammenfassung
Hintergrund
Die medikamentös induzierte Schlafendoskopie (MISE) stellt eine Diagnostikmethode dar, mit der die Kollapsneigung der oberen Atemwege durch medikamentös herbeigeführte Sedierung beurteilbar ist. Nach Expertenmeinung ist es dadurch möglich, Lokalisation, Ausmaß und Muster der pharyngolaryngealen Obstruktion während des Schlafs zu imitieren. Dies soll eine zielgerichtetere Therapieempfehlung als bei alleiniger klinischer Untersuchung ermöglichen.
Ziel der Arbeit
Die vorliegende Arbeit evaluiert kritisch den momentanen Stand und Indikationsmöglichkeiten der MISE.
Material und Methoden
Eine PubMed-Literaturrecherche mit den Schlagwörtern „sleep" und „endoscopy" oder „DISE" wurde durchgeführt und relevante Publikationen ausgewertet.
Ergebnisse
Die vorliegende Arbeit bietet einen historischen Abriss über die Literatur und setzt diese in Bezug zu anderen Untersuchungstechniken bei obstruktiver Schlafapnoe. Die aktuelle Entwicklung der MISE in Hinblick auf Medikation, Klassifikationssysteme und Validierung wird evaluiert. Indikationsstellungen für eine MISE werden kritisch beleuchtet und anhand von Literaturdaten diskutiert.
Schlussfolgerung
Die MISE bietet einen tieferen Einblick in die Entstehung von Atemwegsobstruktionen und Schnarchen. Ihre Wertigkeit in Diagnostik und Therapie schlafbezogener Atmungsstörungen (SBAS) konnte zwar bisher nicht pauschal für Nicht-CPAP-Verfahren („continuous positive airway pressure") nachgewiesen werden, jedoch wurden für einige Therapieverfahren prädiktive Parameter in der MISE definiert. Hierzu zählen z. B. Unterkieferprotrusionsschienen und die atmungssynchrone Stimulation des N. hypoglossus. Damit ist die MISE auch in Zukunft ein wertvolles Diagnostikinstrument bei obstruktiver Schlafapnoe und Schnarchen.
http://ift.tt/2kiYXdd
Low-level laser therapy in the treatment of pressure ulcers: systematic review
Abstract
The aim of this study was to evaluate the effects of low-level laser therapy (LLT) in pressure ulcers (PU) in humans through a systematic review of randomized studies. The search includes the databases MEDLINE, PEDro, Cochrane CENTRAL, and Lilacs, as well a manual search until May, 2016. This included randomized clinical trials of LLT compared with other interventions, different types of LLT, LLT placebo, or control in the treatment of PU. The outcomes evaluated were the ulcer area, healing rate, and overall healing rate. The risk of bias was evaluated using the tool of the Cochrane Collaboration, and the results were analyzed descriptively. From the 386 articles identified, only four studies were included, with two LLT used with single wavelength (1: 904 nm vs. control and 2: 940 nm vs. 808 nm vs. 658 nm vs. placebo) and two LLT used to probe cluster. One study compared to different single wavelengths showed a significant 71% reduction of the PU and an improved healing rate in which 47% of PU healed completely after 1 month of therapy with the use of LLT with a wavelength of 658 nm compared with other lengths. The other analyzed wavelengths were not significant in the assessed outcomes. Significant results were observed in the use of LLT with a 658 nm wavelength, and no evidence was found for use of wavelengths above that for the treatment of PU. Therefore, we also found no evidence in the laser used to probe the cluster.
Registration number: CRD42016036648.
http://ift.tt/2k7Agkt
Investigation of photobiomodulation potentiality by 635 and 809 nm lasers on human osteoblasts
Abstract
Photobiomodulation (PBM) describes light-induced photochemical reactions achieved by the application of red or near infrared lasers/LED light with low energy densities. This noninvasive and painless method has been used in some clinical areas but controversial outcomes demand a skeptical look for its promising and potential effects. In this detailed in vitro study, the osteoblast cells were irradiated with 635 and 809 nm diode lasers at energy densities of 0.5, 1, and 2 J/cm2. Cell viability, proliferation, bone formation, and osteoblast differentiation were evaluated by methylthiazole tetrazolium (MTT) assay, Alamar Blue assay, acridine orange/propidium iodide staining, alkaline phosphatase (ALP) activity, Alizarin red staining, and reverse-transcription polymerase chain reaction (RT-PCR) to test the expression of collagen type I, ALPL, and osteocalcin. The results indicate that studied energy doses have a transient effect (48 h after laser irradiation) on the osteoblast viability and proliferation. Similarly, laser irradiation did not appear to have any effect on ALP activity. These results were confirmed by RT-PCR analysis of osteoblast markers. This study suggests that several irradiation parameters and variations in the methods should be clearly established in the laboratory before laser treatment becomes a postulated application for bone tissue regeneration in clinical level.
http://ift.tt/2jgCJL8
Tratamiento con toxina botulínica del síndrome del primer mordisco
Publication date: Available online 22 January 2017
Source:Acta Otorrinolaringológica Española
Author(s): María Costales-Marcos, Fernando López Álvarez, Laura Fernández-Vañes, Justo Gómez, José Luis Llorente
El síndrome del primer mordisco es una secuela potencial de la cirugía del espacio infratemporal, lóbulo profundo de parótida y del espacio parafaríngeo. Se trata de un dolor agudo e intenso en la región parotídea que se desencadena con el primer mordisco de cada comida. Se relaciona con el daño de las fibras simpáticas que inervan la parótida, lo que resulta en una hipersensibilidad de las células mioepiteliales a la inervación parasimpática, provocando una intensa contracción de las mismas, responsable del dolor causado. No responde a los analgésicos habituales. La inyección de toxina botulínica tipo A en la parótida afectada se presenta como un tratamiento sencillo y eficaz contra este problema por el bloqueo colinérgico que produce. Presentamos la técnica y los resultados de 5 pacientes a los que se les inyectó la toxina botulínica en la parótida afectada.First bite syndrome is a potential complication of surgery involving the infratemporal fossa, deep lobe of the parotid gland and parapharyngeal space. It is described as an acute and intense pain in the parotid region caused with the first bite of each meal. It is related to damage to sympathetic innervation of the parotid gland. Parasympathetic hyperactivation is believed to stimulate an exaggerated myoepithelial cell contraction causing pain. Usual analgesic treatments have poor results. Botulinum toxin type A causes parasympathetic nerve paralysis of the parotid gland and this fact would minimize salivation and decrease first bite syndrome. The aim of this study is to show the details of the technique and our outcomes in 5 patients treated with botulinum toxin type A.
http://ift.tt/2kj2dcB
Autophagy-related genes in Helicobacter pylori infection
Abstract
Background
In vitro studies have shown that Helicobacter pylori (H. pylori) infection induces autophagy in gastric epithelial cells. However, prolonged exposure to H. pylori reduces autophagy by preventing maturation of the autolysosome. The alterations of the autophagy-related genes in H. pylori infection are not yet fully understood.
Materials and Methods
We analyzed autophagy-related gene expression in H. pylori-infected gastric mucosa compared with uninfected gastric mucosa obtained from 136 Bhutanese volunteers with mild dyspeptic symptoms. We also studied single nucleotide polymorphisms (SNPs) of autophagy-related gene in 283 Bhutanese participants to identify the influence on susceptibility to H. pylori infection.
Results
Microarray analysis of 226 autophagy-related genes showed that 16 genes were upregulated (7%) and nine were downregulated (4%). We used quantitative reverse transcriptase polymerase chain reaction to measure mRNA levels of the downregulated genes (ATG16L1, ATG5, ATG4D, and ATG9A) that were core molecules of autophagy. ATG16L1 and ATG5 mRNA levels in H. pylori-positive specimens (n=86) were significantly less than those in H. pylori-negative specimens (n=50). ATG16L1 mRNA levels were inversely related to H. pylori density. We also compared SNPs of ATG16L1 (rs2241880) among 206 H. pylori-positive and 77 H. pylori-negative subjects. The odds ratio for the presence of H. pylori in the GG genotype was 0.40 (95% CI: 0.18-0.91) relative to the AA/AG genotypes.
Conclusions
Autophagy-related gene expression profiling using high-throughput microarray analysis indicated that downregulation of core autophagy machinery genes may depress autophagy functions and possibly provide a better intracellular habit for H. pylori in gastric epithelial cells.
http://ift.tt/2kiDHUU
Appropriate Testing of Isothiazolinones in Children
Abstract
Background/Objective
The isothiazolinones methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are prevalent pediatric contact sensitizers. MI allergic contact dermatitis (ACD) is underreported in the literature. The objective of the current study was to use a database of provider-reported U.S. pediatric patch test cases to evaluate the positive patch test (PPT) prevalence rates of the combined preservative test substrate MCI/MI and of MI alone.
Methods
U.S. pediatric patch test providers in all 50 states who had joined the registry were invited to submit deidentified cases to the database. More than 1100 logged cases in the database were evaluated for PPTs to MCI/MI combination, MCI/MI and MI, and MI alone.
Results
Within 1 year of data collection, 96 cases with a PPT for MCI/MI, MCI/MI and MI, and MI alone were identified; 37 of these were positive to MCI/MI, with MI alone not tested or negative, and 39 were positive to MI only, with MCI/MI and MI tested. Fifteen (41%) of the MCI/MI cases were detected using an epicutaneous patch test alone and 22 cases (59%) using comprehensive patch testing. Only one case (3%) of MI alone sensitization was detected using T.R.U.E. plus a supplemental panel of tests; the remaining 38 cases (97%) were detected using comprehensive testing. Testing with only the combined MCI/MI preservative substrate may miss 51% of MI allergies.
Conclusion
Appropriate testing of isothiazolinones is needed to clarify the true prevalence of sensitization to these allergens and the burden of pediatric ACD. Patch testing for MI alone in addition to MCI/MI combination is warranted in children with recalcitrant dermatitis.
http://ift.tt/2j4k55J
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