Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, a rare inherited urea cycle disorder, can remain undiagnosed for decades and suddenly turn into an acute life-threatening state. Adult presentation ...
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Σάββατο 22 Σεπτεμβρίου 2018
Late onset hyperornithinemia-hyperammonemia-homocitrullinuria syndrome - how web searching by the family solved unexplained unconsciousness: a case report
Sepsis and Pleural Empyema Caused by Streptococcus pyogenes after Influenza A Virus Infection
Streptococcus pyogenes (also referred to as group A streptococci, GAS) causes severe invasive diseases such as bacteremia, necrotizing fasciitis, pneumonia, osteomyelitis, septic arthritis, and toxic shock syndrome in children. However, there are only a few reports on pleural empyema caused by GAS in children. Here, we report the case of a 4-year-old boy who presented with pleural empyema due to GAS after influenza A virus infection. With intravenous antibiotic administration and continuous chest-tube drainage, followed by video-assisted thoracoscopic surgery, his condition improved. During the clinical course, cytokines induced in response to the influenza virus, especially IL-1β and IL-10, were elevated 1 week after influenza A infection, but these decreased as the symptoms improved. Reportedly, the IL-10 production increases during influenza virus-bacteria superinfection. These observations suggest that the immunological mechanisms induced by the influenza virus can play an important role in influencing the susceptibility to secondary bacterial infections, such as GAS, in children.
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Hypogammaglobulinemia and imaging features in a patient with infantile free sialic acid storage disease (ISSD) and a novel mutation in the SLC17A5 gene
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
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Achieving target levels for vascular risk parameters in Polish school-age children with type 1 diabetes – a single center study
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
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Fratura nasal e septal – Dr Marco Antônio Corvo
Fratura nasal e septal – Dr Marco Antônio Corvo
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IL-6: a cytokine at the crossroads of autoimmunity
Britta E Jones | Megan D Maerz | Jane H Buckner
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Emerging areas for therapeutic discovery in SLE
Naomi I Maria | Anne Davidson
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The role of Wnt/β-catenin signaling in the restoration of induced pluripotent stem cell-derived retinal pigment epithelium after laser photocoagulation
Abstract
To investigate the role of Wnt/β-catenin signaling pathway in the restoration of induced pluripotent stem cell-derived retinal pigment epithelium (hiPSC-RPE) after laser photocoagulation. After differentiation of RPE cells from hiPSCs, laser photocoagulation was performed. Activation of Wnt/β-catenin signaling at days 1 and 5 after laser photocoagulation was evaluated by expression of β-catenin. Cell proliferation and alteration in cell-to-cell contact at day 5 after laser photocoagulation with or without Dickkopf-1 (Dkk-1) treatment were studied using ethynyl-2′-deoxyuridine (EdU) assay and zonula occludens-1 (ZO-1) expression analysis, respectively. The mRNA levels of Wnt genes at day 5 after laser photocoagulation were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Activation of Wnt/β-catenin signaling at days 1 and 5 after laser photocoagulation was confirmed by β-catenin accumulation in the cytoplasm and nucleus of hiPSC-RPE. Many EdU-positive cells also expressed β-catenin, and the number of EdU-positive cells was decreased at day 5 after laser photocoagulation after Dkk-1 treatment, indicating that Wnt/β-catenin signaling mediated hiPSC-RPE proliferation. ZO-1 expression was not decreased with Dkk-1 treatment at day 5 after laser photocoagulation, indicating that Wnt/β-catenin signaling mediated hiPSC-RPE restoration. At day 5, after laser photocoagulation, mRNA levels of Wnt2b, Wnt3, Wnt5a, Wnt7a, and Wnt10b were increased. Wnt/β-catenin signaling has a crucial role in restoration of hiPSC-RPE proliferation after laser photocoagulation. Manipulation of Wnt/β-catenin signaling while elucidating the underlying mechanisms of RPE restoration might have a therapeutic potential in retinal degenerative diseases.
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Wound-healing effects of 635-nm low-level laser therapy on primary human vocal fold epithelial cells: an in vitro study
Abstract
Low-level laser therapy (LLLT) has been promoted for its beneficial effects on tissue healing and pain relief for skin and oral applications. However, there is no corresponding literature reporting on vocal fold wound healing. Our purpose was to assess the potential wound-healing effects of LLLT on primary human vocal fold epithelial cells (VFECs). In this study, normal vocal fold tissue was obtained from a 58-year-old male patient who was diagnosed with postcricoid carcinoma without involvement of the vocal folds and underwent total laryngectomy. Primary VFECs were then cultured. Cells were irradiated at a wavelength of 635 nm with fluences of 1, 4, 8, 12, 16, and 20 J/cm2 (50 mW/cm2), which correspond to irradiation times of 20, 80, 160, 240, 320, and 400 s, respectively. Cell viability of VFECs in response to varying doses of LLLT was investigated by the Cell Counting Kit-8 (CCK-8) method. The most effective irradiation dose was selected to evaluate the cell migration capacity by using the scratch wound-healing assay. Real-time polymerase chain reaction (RT-PCR) was used to detect the gene expression of TGF-β1, TGF-β3, EGF, IL-6, and IL-10. Irradiation with doses of 8 J/cm2 resulted in 4% increases in cell proliferation differing significantly from the control group (p < 0.05). With subsequent doses at 48 and 72 h after irradiation, the differences between the experimental and the control groups became greater, up to 9.8% (p < 0.001) and 19.5% (p < 0.001), respectively. It also increased cell migration and the expression of some genes, such as EGF, TGF-β1, TGF-β3, and IL-10, involved in the tissue healing process. This study concludes that LLLT at the preset parameters was capable of stimulating the proliferation and migration of human vocal fold epithelial cells in culture as well as increase the expression of some genes involved in tissue healing process. Additionally, successive laser treatments at 24 h intervals have an additive beneficial effect on the healing of injured tissues.
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Gingko flap: The development of a novel flap technique to reduce dog ear formation
Dear Sir,
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Comment on “How to assess the volume of a DIEP flap using a free online calculator: the DIEP V (volume) method”
Razzano et al. developed a simple method to calculate the predicted volume of a DIEP flap for breast reconstruction.1 They hypothesized that the best representative shape for a DIEP flap was a truncated pyramid. They measured flap thickness using ultrasound (US), and used other variables including flap length and height to calculate the volume of a truncated pyramid-shaped flap. Great value must be given to this study because estimation of DIEP flap volume is crucial in surgical planning and execution for ultimately matching the volume of the breast being reconstructed, and it also can help decrease donor site complications.
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Anatomic Location of a Sensory Nerve to the Transverse Upper Gracilis (TUG) Flap: A Novel Option for Sensate Autologous Tissue Reconstruction
A January 2017 article in the New York Times, "After Mastectomies, an Unexpected Blow: Numb New Breasts," made the concept of hypoesthesia after mastectomy mainstream. This, along with advances in cadaveric nerve grafts, has led to a surge in the number of publications regarding sensate autologous breast reconstruction. Autologous breast reconstruction typically utilizes an abdominal donor site and the majority of research in sensate autologous tissue has been performed in DIEP or TRAM flaps [3, 4].
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The Helsinki Approach to Face Transplantation
We herein describe the establishment of the Helsinki Vascularized Composite Allotransplantation (VCA) program and its execution in the first two face transplant cases.
https://ift.tt/2NuljeK
When should we use the terms “aponeurotic blepharoptosis” and “reinsertion of the levator aponeurosis”?
It is generally considered that involutional (or senile) blepharoptosis is caused by disinsertion of the levator aponeurosis1. This type of acquired blepharoptosis is therefore also referred to as "aponeurotic blepharoptosis", by reference to its presumed etiology. However, the levator aponeurosis is rarely found to be disinserted peroperatively 2 (at most a dehiscence is found) and it has been suggested that in some cases this disinsertion could be iatrogenic and caused by the surgical procedure itself 3.
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Cyclic fatigue of Reciproc Blue and Reciproc instruments exposed to intracanal temperature in simulated severe apical curvature
Abstract
Objective
The aim of this study was to evaluate the cyclic fatigue resistance of Reciproc and Reciproc Blue by testing in a severe apical curvature at intracanal temperature.
Materials and methods
Eighteen Reciproc R25 (25.08) and Reciproc Blue (25.08) instruments were tested in a cyclic fatigue device at body temperature (37 °C) using a stainless steel block with an artificial canal with a curvature angle of 90° and radius of curvature of 2 mm. The number of cycles to fracture (NCF) was calculated. The instruments were examined by differential scanning calorimetry (DSC). The data were analyzed using both Student's t tests and Weibull analysis.
Results
The NCF values of Reciproc R25 were significantly lower than Reciproc Blue R25 (P < 0.05). There was no significant difference between the instruments regarding the length of fractured fragments (P > 0.05).
Conclusions
Reciproc Blue R25 instruments displayed significantly higher NCF than Reciproc R25.
Clinical relevance
This study reported that novel reciprocating blue wire instruments exhibited higher cyclic fatigue resistance than its precedence M-wire instrument when tested in severely curvatured canals.
https://ift.tt/2MU8FR1
Biochemical changes in injured sciatic nerve of rats after low-level laser therapy (660 nm and 808 nm) evaluated by Raman spectroscopy
Abstract
The aim of this study was to identify biochemical changes in sciatic nerve (SN) after crush injury and low-level laser therapy (LLLT) with 660 nm and 808 nm by Raman spectroscopy (RS) analysis. A number of 32 Wistar rats were used, divided into four groups (control 1, control 2, LASER 660 nm, and LASER 808 nm). All animals underwent surgical procedure of the SN and groups control 2, LASER 660 nm, and LASER 808 nm were submitted to SN crush damage (axonotmesis). The LLLT in the groups LASER 660 nm and LASER 808 nm was applied daily for 21 consecutive days (100 mW, 30 s, 133 J/cm2 fluence). The hind paw was removed and the SN was dissected and positioned on an aluminum support to collect dispersive Raman spectra (830 nm excitation, 30 s accumulation). To estimate the biochemical changes in the SN associated with LLLT, the principal component analysis (PCA) was applied. The Raman spectra of the sciatic nerve fragments showed peaks of the major biochemical components of the nerve, especially sphingolipids, phospholipids, glycoproteins, and collagen. The spectral features identified in some of the principal component loading vectors are referred to the biochemical elements present on the SN and were increased in the groups treated with LLLT, mainly lipids (sphingo and phospholipids) and proteins (collagen)—constituents of the myelin sheath. The RS was effective in identifying the biochemical differences in the SN after the crush injury, and LASER 660 nm was more efficient than the LASER 808 nm in cell proliferation and repair of the injured SN.
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Evaluation of circulating invariant T cells before and after IL-17 inhibitor treatment in a patient with psoriatic arthritis
Publication date: Available online 21 September 2018
Source: Clinical Immunology
Author(s): Tomohiro Koga, Megumi Matoba, Tomohito Sato, Koike, Yushiro Endo, Remi Sumiyoshi, Shin-ya Kawashiri, Naoki Iwamoto, Kunihiro Ichinose, Mami Tamai, Hideki Nakamura, Tomoki Origuchi, Atsushi Kawakami
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Tolerogenic dendritic cells induced the enrichment of CD4+Foxp3+ regulatory T cells via TGF-β in mesenteric lymph nodes of murine LPS-induced tolerance model
Publication date: Available online 21 September 2018
Source: Clinical Immunology
Author(s): Li Jia, Jia Lu, Ya Zhou, Yijing Tao, Hualin Xu, Wen Zheng, Juanjuan Zhao, Guiyou Liang, Lin Xu
Abstract
Endotoxin tolerance is an important state for the prevention of lethal infection and inflammatory response, which is closely associated with the participation of innate immune cells. Moreover, mesenteric lymph nodes (MLNs)-resident immune cells, such as CD4+Foxp3+ regulatory T (Treg) cells and dendritic cells, play important roles in the maintenance of peripheral immune tolerance. However, the potential roles of these cells in MLNs in the development of endotoxin tolerance remain largely unknown. Recent research work showed that CD4+Foxp3+ Treg cells contributed to the development of endotoxin tolerance. Here, we further analyzed the possible change on CD4+Foxp3+Tregs population in MLNs in murine LPS-induced endotoxin tolerance model. Our data showed that the proportion and absolute number of CD4+Foxp3+Tregs, expressing altered levels of CTLA4 and GITR, significantly increased in MLNs of murine LPS-induced tolerance model. Moreover, the expression level of TGF-β in MLNs also increased obviously. Furthermore, TGF-β blockade could obviously reduce the proportion and absolute number of CD4+Foxp3+Tregs in MLNs and subsequently impair the protection effect against LPS rechallenge. Of note, we found that tolerogenic dendritic cell (Tol-DC), expressing lower levels of MHC-II and CD86 molecules, dominantly secreted TGF-β in MLNs in murine LPS-induced tolerance model. In all, our data provided an unknown phenomenon that the total cell number of CD4+Foxp3+Tregs significantly increased in MLNs in endotoxin tolerance, which was related to MLN-resident TGF-β secreting CD11c+DCs, providing a new fundamental basis for the understanding on the potential roles of MLN-resident immune cells in the development of endotoxin tolerance.
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Different Upper Airway Microbiome and Their Functional Genes Associated with Asthma in Young Adults and Elderly Individuals
Allergy, Volume 0, Issue ja, -Not available-.
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Increased expression of aquaporin-1 in dermal fibroblasts and dermal microvascular endothelial cells possibly contributes to skin fibrosis and edema in patients with systemic sclerosis
Publication date: Available online 21 September 2018
Source: Journal of Dermatological Science
Author(s): Takashi Yamashita, Yoshihide Asano, Ryosuke Saigusa, Takashi Taniguchi, Kouki Nakamura, Shunsuke Miura, Tetsuo Toyama, Takehiro Takahashi, Yohei Ichimura, Megumi Hirabayashi, Ayumi Yoshizaki, Tomomitsu Miyagaki, Makoto Sugaya, S. Sato
Abstract
Background
Aquaporin-1 (AQP1), a water channel protein controlling the water contents of cells and tissues, exerts pleiotropic effects on various biological activities, including inflammation, angiogenesis, and extracellular matrix remodeling, by regulating cell behaviors and tissue water balance.
Objective
To investigate AQP1 roles in systemic sclerosis (SSc) which is characterized by autoimmune inflammation, vasculopathy, and tissue fibrosis.
Methods
AQP1 expression was evaluated by immunohistochemistry and quantitative reverse transcription PCR in skin samples from human and animal models and by immunoblotting in cultured cells. Fli1 binding to the AQP1 promoter was evaluated by chromatin immunoprecipitation. Cell migration was assessed by scratch assay.
Results
Dermal fibroblasts and endothelial cells highly expressed AQP1 in SSc lesional skin, and AQP1 expression in dermal fibroblasts and endothelial cells positively correlated with the degrees of tissue fibrosis and edema, respectively. Consistently, SSc dermal fibroblasts up-regulated AQP1 compared with normal dermal fibroblasts in vitro. Furthermore, TGF-β stimulation induced AQP1 expression in normal dermal fibroblasts, while TGF-β1 antisense oligonucleotide suppressed AQP1 expression in SSc dermal fibroblasts. In endothelial cells, Fli1 deficiency resulted in AQP1 up-regulation in vivo and in vitro and Fli1 bound to the AQP1 promoter. Importantly, SSc dermal fibroblasts and FLI1 siRNA-treated endothelial cells had a pro-migratory property, which was remarkably diminished by gene silencing of AQP1.
Conclusion
AQP1 is up-regulated in SSc dermal fibroblasts and SSc endothelial cells at least partially due to autocrine TGF-β stimulation and Fli1 deficiency, respectively, possibly contributing to inflammation, vasculopathy, and tissue fibrosis by regulating tissue edema and cell migration.
https://ift.tt/2MUBi0h
A comparative study between adenoids and nasal mucosa for ciliated epithelium in children with recurrent or chronic rhinosinusitis
Publication date: Available online 21 September 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Christine M. Kim, Earl H. Harley
Abstract
Objective
To determine whether adenoid epithelium is superior to nasal mucosa for biopsy of ciliated epithelium for electron microscopy (EM) to evaluate pediatric patients with rhinosinusitis for primary ciliary dyskinesia (PCD).
Methods
A retrospective review compared electron microscopic results in children with chronic or recurrent rhinosinusitis who underwent both adenoidectomy or nasopharyngeal biopsy and nasal mucosa biopsy in the course of evaluation for PCD at a tertiary care institution.
Results
Forty pediatric patients met inclusion criteria for this study. Nine of these patients had a prior adenoidectomy and therefore underwent nasopharyngeal biopsy for collection of adenoid tissue. All nine of the nasopharyngeal biopsies and 25 of the 31 (80.6%) adenoid biopsies had sufficient cilia for EM evaluation of the ultrastructure. Of the 40 patients who also had a nasal biopsy, only 12 (30.0%) had sufficient cilia for EM analysis. The distribution of sufficient versus insufficient cilia for analysis between adenoid and nasal mucosa was statistically significant (P<0.05). Abnormal cilia were found in only 2.5 percent of our patients.
Conclusions
In current practice, the nasal cavity is a common location for obtaining ciliated epithelium for EM analysis, as it is easily accessible for biopsy and the procedure itself causes relatively low patient morbidity. Chronic rhinosinusitis, however, has been associated with decreased cilia density on nasal respiratory epithelium. Given that adenoidectomies are often performed in children with chronic rhinosinusitis, our data suggest that adenoid tissue is a better source of ciliated tissue for analysis compared to turbinate epithelium.
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Risk factors for cervical lymph node metastasis in endoscopically resected superficial hypopharyngeal cancers
Publication date: Available online 22 September 2018
Source: Auris Nasus Larynx
Author(s): Takayuki Imai, Shigemi Ito, Tomoyuki Oikawa, Yukinori Asada, Ko Matsumoto, Takefumi Miyazaki, Tomoko Yamazaki, Ikuro Satoh, Tetsuya Noguchi, Kazuto Matsuura
Abstract
Objective
Hypopharyngeal cancer is a head and neck cancer with a poor prognosis, and most cases show metastases on diagnosis. Cervical lymph node (LN) metastasis is a poor prognostic factor in hypopharyngeal cancer patients. The identification of risk factors for LN metastasis can help guide surgical treatment strategies for these patients.
Methods
This retrospective study included 93 superficial hypopharyngeal cancer patients with 109 histopathologically examined lesions treated by endoscopic resection between January 2007 and December 2017. Tumor thickness quantification, quantification of budding nests, immunostaining and other histopathological analyses in paraffin-embedded, formalin-fixed tissue sections (3-μm) of surgical specimens were performed by a certified pathologist.
Results
Cervical LN metastasis was positive in 18 out of 93 cases (19.3%) and 18 out of 109 lesions (16.5%). No differences were detected in patient characteristics between LN-positive and LN-negative cases, except for tumor thickness, which was significantly larger in LN-positive cases (3119.4 ± 602.2 μm vs. 1015.5 ± 129.6 μm, respectively; p < 0.0001). Univariate analysis showed that tumor thickness ≥1000 μm (odds ratio: 5.559, p = 0.003), lesions with high budding grade (odds ratio: 5.188, p = 0.01) and vascular invasion (odds ratio: 12.710, p = 0.007) were significantly associated with cervical LN metastasis. Multivariate analysis revealed tumor thickness ≥ 1000 μm as the most significant risk factor for cervical LN metastasis in superficial hypopharyngeal cancer (odds ratio: 3.639, p = 0.04).
Conclusions
We demonstrate for the first time that high budding grade may serve as powerful predictors of LN metastasis and tumor thickness ≥1000 μm is a significant risk factor for LN metastasis of superficial hypopharyngeal cancer. These results should be further examined in future larger scale studies.
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The molecular mechanisms of increased radiosensitivity of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC): an extensive review
Head and neck carcinomas (HNCs) collectively are the sixth most common cancer with an annual incidence of about 400,000 cases in the US. The most well-established risk factors for HNCs are tobacco and alcohol ...
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Penicillin minor determinants: History and relevance for current diagnosis
Publication date: Available online 21 September 2018
Source: Annals of Allergy, Asthma & Immunology
Author(s): N. Franklin Adkinson, Louis M. Mendelson, Charlotte Ressler, John C. Keogh
Abstract
Objective
To review the history of the penicillin minor determinants and evaluate their relevance for current diagnosis.
Data Sources
Skin testing to detect immunoglobulin E (IgE) sensitivity to penicillins in patients with a history of penicillin allergy has been the subject of more than 55 years of published research involving tens of thousands of patients.
Study Selections
Selection of data was based on its relevance to the objective of this article.
Results
It was established early on that testing with the major penicilloyl determinant using the polyvalent penicilloyl-polylysine (PPL) is negative in a substantial portion (10-64%, including recent increases) of those at risk for immediate hypersensitivity reactions. A variety of minor penicillin determinants are clinically significant in that their use in skin testing is essential to detect all those at risk. In particular, a minor determinant mixture (MDM) of benzylpenicillin, benzylpenicilloate, and benzylpenilloate, used in conjunction with PPL, has been shown in numerous studies to achieve an average negative predictive value (NPV) of 97.9% in history-positive patients. Benzylpenicillin alone, as the sole minor determinant, leaves many skintest- positive patients undiscovered. Use of amoxicillin as an additional minor determinant reagent appears to identify another 2-8% of skin-testpositive patients in some populations.
Conclusion
IgE skin testing, using both the major and appropriate minor determinants of penicillin, can identify, with a high degree of reliability (NPV ∼ 97%), penicillin-allergy-history-positive patients who can receive beta-lactam antibiotics without concern for serious acute allergy, including anaphylaxis. The few false negative skin tests reported globally are largely confined to minor, self-limited cutaneous reactions.
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Dependence of the frequency distribution around a vessel on the voxel orientation
Publication date: Available online 21 September 2018
Source: Magnetic Resonance Imaging
Author(s): L.R. Buschle, T. Kampf, F.T. Kurz, P. Vogel, F. Piekarek, V.J.F. Sturm, M. Pham, H.-P. Schlemmer, C.H. Ziener
Abstract
In this work the frequency distribution around a vessel inside a cubic voxel is investigated. Therefore, the frequency distribution is calculated in dependence on the orientation of the voxel according to the external magnetic field. The frequency distribution exhibits an interesting peak structure that cannot be explained by the established Krogh's vessel model. The results were validated with phantom measurements and in vivo measurements that agree very well with the developed theory.
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Cytokine levels in persistent skin lesions of adult-onset Still disease
Publication date: Available online 21 September 2018
Source: Journal of the American Academy of Dermatology
Author(s): Elina Zuelgaray, Maxime Battistella, Marie-Dominique Vignon-Pennamen, Sophie Ly Ka So, Michel Rybojad, Antoine Petit, Florence Cordoliani, David Boccara, Maurice Mimoun, Dan Lipsker, François Chasset, Armand Bensussan, Martine Bagot, Jean-David Bouaziz, Laurence Michel, Study Group of Systemic Diseases in Dermatology (EMSED: Etude des Maladies Systémiques en Dermatologie)
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Anaphylaxis to beta-lactam antibiotics at pediatric age: Six-year survey
Publication date: Available online 21 September 2018
Source: Allergologia et Immunopathologia
Author(s): J. Azevedo, Â. Gaspar, I. Mota, F. Benito-Garcia, M. Alves-Correia, M. Chambel, M. Morais-Almeida
Abstract
Introduction
Beta-lactams are the most frequently used antibiotics in pediatric age. Anaphylactic reactions may occur and need to be properly studied, but studies in children are scarce.
Objective
Characterization of case reports of anaphylaxis in children referred to an allergy department with suspected beta-lactams hypersensitivity.
Materials and methods
Retrospective analysis of all children referred to our Drug Allergy Center with suspected beta-lactams hypersensitivity between January 2011 and December 2016. Description of the drug allergy work-up performed studied according to standardized diagnostic procedures of ENDA/EAACI, including specific-IgE assay, skin prick and intradermal tests and diagnostic/alternative drug challenge tests.
Results
146 children with suspected beta-lactams hypersensitivity were studied, and in 21 (14.4%) the diagnosis was confirmed. In all of them, except for three children, an alternative beta-lactam was found. In seven children (33.3% of those with confirmed beta-lactams hypersensitivity) anaphylaxis was confirmed, and all of them described reactions with cutaneous and respiratory or gastrointestinal involvement. The culprit drug was amoxicillin in six and flucloxacillin in one. In this sample, we also performed oral challenge with cefuroxime, being negative in all cases. Almost all cases of confirmed anaphylaxis (six from seven cases) were IgE mediated, with positive skin tests despite negative serum specific-IgE.
Conclusions
Allergic reactions to beta-lactams, although rare in children, require a detailed clinical history and a specialized drug allergy work-up to allow a correct diagnosis as well as to avoid the possibility of a potential life-threatening reaction and provide alternative drugs.
https://ift.tt/2MUg8Qb
BJORL: moving forward, always
Publication date: Available online 21 September 2018
Source: Brazilian Journal of Otorhinolaryngology
Author(s): Wilma Terezinha Anselmo-Lima, Shirley Shizue Nagata Pignatari
https://ift.tt/2Dojmf5
Ultrasonographic study of intestinal Doppler blood flow in infantile non-IgE-mediated gastrointestinal food allergy
Publication date: Available online 22 September 2018
Source: Allergology International
Author(s): Keisuke Jimbo, Yoshikazu Ohtsuka, Tatsuo Kono, Nobuyasu Arai, Reiko Kyoudo, Kenji Hosoi, Yo Aoyagi, Takahiro Kudo, Nobuyoshi Asai, Toshiaki Shimizu
Abstract
Background
Although non-IgE-mediated gastrointestinal food allergy has increased rapidly in Japan, a small number of reports has evaluated B-mode and Doppler ultrasonographic findings in the acute phase of infantile gastrointestinal milk allergy. The aim of the present study was to compare the diagnostic utility of ultrasonographic findings and laboratory allergic data in non-IgE-mediated infantile gastrointestinal milk allergy.
Methods
Sixteen cases of active non-IgE-mediated infantile gastrointestinal milk allergy, diagnosed by food elimination tests and oral food challenge tests (OFCTs) (group A), 15 cases of acute viral gastroenteritis (AGE) (group B), and 15 controls (group C) were enrolled. 1) B-mode abdominal ultrasound findings, 2) laboratory allergic data including eosinophil counts (Eos), serum IgE, and the antigen-specific lymphocyte proliferation test (ALPT) against milk protein, and 3) vessel density (VD) indirectly quantified by gastrointestinal Doppler flow at jejunum, ileum, and sigmoid colonic mucosae were evaluated and compared among the groups.
Results
In the small intestine, wall thickening, dilation, mesenteric thickening, and poor peristalsis were found in 100%, 62.5%, 93.7%, and 100%, respectively, in group A. Eos, IgE, ALPT, and VD were positive in 25.0%, 0%, 87.5%, and 100%, respectively, in group A. Small intestinal VD was significantly greater in group A than in groups B (jejunum p < .001; ileum p < .001) and C (jejunum p < .001; ileum p < .001), with no significant differences between groups B and C (jejunum: p = .74; ileum: p = .73).
Conclusions
Abdominal Doppler ultrasonography and small intestinal VD at symptomatic state can support the diagnosis and evaluation of non-IgE-mediated infantile gastrointestinal milk allergy with symptoms of vomiting, diarrhea, and failure to thrive.
https://ift.tt/2QRdM7B
Stem cell factor suppressed IL-33-induced MHC class II expression in murine bone marrow-derived mast cells
Publication date: Available online 21 September 2018
Source: Allergology International
Author(s): Tomonobu Ito, Chizu Egusa, Tatsuo Maeda, Takafumi Numata, Nobuhiro Nakano, Chiharu Nishiyama, Ryoji Tsuboi
https://ift.tt/2xJi48j
Characterization of cDNA clones encoding major histocompatibility class II receptors from walleye (Sander vitreus)
Publication date: November 2018
Source: Molecular Immunology, Volume 103
Author(s): Quinn H. Abram, Kazuhiro Fujiki, Marije Booman, Emily Chin-Dixon, Guang Wei, Brian Dixon
Abstract
The teleost major histocompatibility (MH) class II receptor presents peptides from exogenous sources to CD4+ T cells, leading to the initiation of the adaptive immune response. The genes encoding MH class II have been identified in a number of teleost species, but not in walleye, an important recreational fish and commercial fishery in North America. In this study, we cloned and characterized the sequences encoding walleye MH class II α and β chains. These sequences contained all of the domains typical for functional MH class II α and β chain proteins, and aligned with other teleost sequences of MH class II. The walleye MH class II α amino acid sequence, along with other members of the Supraorder Percomorpharia, contains a high concentration of methionine residues in the beginning of the leader peptide. Southern blotting indicated that there is more than one gene copy for both MH class II α and β, while northern blotting analysis of both genes showed that expression of these genes is greatest in lymphoid tissues and at potential entry points for pathogens. These results help to further the understanding of MH class II receptors in teleosts, and could prove useful in the study of disease issues in walleye such as dermal sarcoma virus.
https://ift.tt/2MUrGCV
The role of mitochondria in NLRP3 inflammasome activation
Publication date: November 2018
Source: Molecular Immunology, Volume 103
Author(s): Qiuyun Liu, Danyan Zhang, Diyu Hu, Xiangmei Zhou, Yang Zhou
Abstract
The NLRP3 inflammasome is a multiprotein platform which is activated upon cellular infection or stress. Its activation leads to caspase-1-dependent secretion of proinflammatory cytokines like interleukin-1β (IL-1β) and IL-18, and an inflammatory form of cell death termed as pyroptosis. Recent studies have unveiled the pivotal roles of mitochondria in initiation and regulation of the NLRP3 (nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing 3) inflammasome. NLRP3 activators induce mitochondrial destabilization, NLRP3 deubiquitination, linear ubiquitination of ASC, and externalization or release of mitochondria-derived molecules such as cardiolipin and mitochondrial DNA. These molecules bind to NLRP3 that is translocated on mitochondria and activate the NLRP3 inflammasome. Here we review recently described mechanisms by which mitochondria regulate NLRP3 inflammasome activation.
https://ift.tt/2xxi6AV
Actinomycosis Presenting as Macroglossia: Case Report and Review of Literature
Abstract
Cervicofacial actinomycosis is a common form of Actinomyces infection. However, the latter seldom occurs in the tongue. We present a case of a 66 year-old man with macroglossia caused by actinomycosis of the tongue. Radiographic features were compatible with a chronic inflammatory disease. Biopsies revealed granulomas containing giant cells and Gram positive bacterial clusters consistent with actinomycosis. The patient was treated with a 22 week course of antibiotics. Imaging showed a notable improvement in the extent of the lesions 1 year later. The patient was asymptomatic and in good condition during his second year follow-up. Diagnosis of actinomycosis of the tongue can prove to be challenging because of the non-specific nature of its symptoms, clinical signs, and radiographic features. Isolation of Actinomyces sp. is an added diagnostic hurdle, because of its fastidious nature.
https://ift.tt/2QQVCmI
Definitive radiation with concurrent cetuximab vs. radiation with or without concurrent cytotoxic chemotherapy in older patients with squamous cell carcinoma of the head and neck: Analysis of the SEER-medicare linked database
Publication date: November 2018
Source: Oral Oncology, Volume 86
Author(s): Dan P. Zandberg, Kevin Cullen, Soren M. Bentzen, Olga G. Goloubeva
Abstract
Objective
To evaluate OS and toxicity after definitive radiation with concurrent cetuximab (CTX-RT) compared to radiation with concurrent cytotoxic chemotherapy (CRT) in older HNSCC patients via the SEER-Medicare linked database.
Materials and Methods
We used the SEER-Medicare linked database to evaluate OS in HNSCC patients (Oropharynx, Larynx, Hypopharynx, Nasopharynx) diagnosed over 2005–2011, following FDA approval of cetuximab in combination with radiation therapy (RT) in March 2006.
Results
2135 beneficiaries were identified. Median age was 73 (66–104) years. Primary was oropharynx (61%), hypopharynx (15%), nasopharynx (5%), and larynx (19%). CRT was platinum based in 82% of patients. CTX-RT was associated with worse OS compared to CRT (P < 0.005), and similar OS to RT (P = 0.21); 5-year OS was 46% for CRT, 35% for CTX-RT, 32% for RT. Patients were more likely to receive CTX-RT vs. CRT if they had oropharyngeal vs nasopharyngeal primary, Charlson comorbidity index 2 vs 0, older age at diagnosis. Multivariable Cox regression showed that CTX-RT was associated with a higher risk of death compared to CRT (hazard ratio = 1.23, 1.07–1.42; p = 0.005), after stratifying by stage and primary site, and adjusting for gender, race, age, income, Charlson comorbidity index, marital status, hospital type, and year of diagnosis. There were no differences in dysphagia, gastrostomy tube placement, pneumonia, and weight loss over the first 12 months after diagnosis.
Conclusion
Despite the limitations to comparative effectiveness evaluation in population-based registries, our data suggest that cytotoxic chemotherapy should be used with RT for eligible older HNSCC patients.
https://ift.tt/2I4vwbG
CRL4DCAF2 is required for mature T-cell expansion via Aurora B-regulated proteasome activity
Publication date: Available online 21 September 2018
Source: Journal of Autoimmunity
Author(s): Keqi Fan, Fei Wang, Yiyuan Li, Lu Chen, Zhengjun Gao, Yu Zhang, Jin-yuan Duan, Tao Huang, Jiangyan Zhong, Rong-bei Liu, Xintao Mao, Hengyu Fan, Xing Guo, Jin Jin
Abstract
The proliferation of T cells in peripheral lymphoid tissues requires T cell receptor (TCR)-mediated cell cycle entry. However, the underlying mechanism regulating cell cycle progression in mature T cells is incompletely understood. Here, we have identified an E3 ubiquitin ligase, CRL4DCAF2, as a critical mediator controlling M phase exit in activated T cells. DCAF2 expression is induced upon TCR stimulation and its deficiency attenuates T cell expansion. Additionally, DCAF2 T cell-specific knockout mice display impaired peripheral T cell maintenance and reduced severity of various autoimmune diseases. Continuous H4K20me1 modification caused by DCAF2 deficiency inhibits the induction of Aurkb expression, which regulates 26S proteasome activity during G2/M phase. CRL4DCAF2 deficiency causes M phase arrest through proteasome-dependent mechanisms in peripheral T cells. Our findings establish DCAF2 as a novel target for T cell-mediated autoimmunity or inflammatory diseases.
https://ift.tt/2QT5xYG
GPR15+ T cells are Th17 like, increased in smokers and associated with multiple sclerosis
Publication date: Available online 21 September 2018
Source: Journal of Autoimmunity
Author(s): Cecilie Ammitzbøll, Marina R. von Essen, Lars Börnsen, Eva Rosa Petersen, Oskar McWilliam, Rikke Ratzer, Romme Christensen Jeppe, Annette B. Oturai, Helle B. Søndergaard, Finn Sellebjerg
Abstract
Smoking is a risk factor for the development and progression of multiple sclerosis (MS); however, the pathogenic effects of smoking are poorly understood. We studied the smoking-associated chemokine receptor-like molecule GPR15 in relation to relapsing-remitting MS (RRMS). Using microarray analyses and qPCR we found elevated GPR15 in blood cells from smokers, and increased GPR15 expression in RRMS. By flow cytometry we detected increased frequencies of GPR15 expressing T and B cells in smokers, but no difference between patients with RRMS and healthy controls. However, after cell culture with the autoantigens myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein, frequencies of MBP-reactive and non-proliferating GPR15+CD4+ T cells were increased in patients with RRMS compared with healthy controls. GPR15+CD4+ T cells produced IL-17 and were enriched in the cerebrospinal fluid (CSF). Furthermore, in the CSF of patients with RRMS, GPR15+ T cells were associated with CCR6+CXCR3+/CCR6−CXCR3+ phenotypes and correlated positively with concentrations of the newly identified GPR15-ligand (GPR15L), myelin degradation and disability. In conclusion, we have identified a proinflammatory cell type linking smoking with pathogenic immune cell functions in RRMS.
https://ift.tt/2xFuwGs
‘Understanding’ differs between English and German: Capturing Systematic Language Differences of Complex Words
Publication date: Available online 22 September 2018
Source: Cortex
Author(s): Fritz Günther, Eva Smolka, Marco Marelli
Abstract
In morphological processing, research has repeatedly found different priming effects by English and German native speakers in the overt priming paradigm. In English, priming effects were found for word pairs with a morphological and semantic relation (SUCCESSFUL-success), but not for pairs without a semantic relation (SUCCESSOR-success). By contrast, morphological priming effects in German occurred for pairs both with a semantic relation (AUFSTEHEN-stehen, 'stand up'-'stand') and without (VERSTEHEN-stehen, 'understand'-'stand'). These behavioural differences have been taken to indicate differential language processing and memory representations in these languages. We examine whether these behavioural differences can be explained with differences in the language structure between English and German. To this end, we employed new developments in distributional semantics as a computational method to obtain both observed and compositional representations for transparent and opaque complex word meanings, that can in turn be used to quantify the degree of semantic predictability of the morphological system of a language. We compared the similarities between transparent and opaque words and their stems, and observed a difference between German and English, with German showing a higher morphological systematicity. The present results indicate that the investigated cross-linguistic effect can be attributed to quantitatively-characterized differences in the speakers' language experience, as approximated by linguistic corpora.
https://ift.tt/2OMSKG9
Loss-of-function mutations in CARD14 are associated with a severe variant of atopic dermatitis
Publication date: Available online 21 September 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Alon Peled, Ofer Sarig, Guangping Sun, Liat Samuelov, Chi A. Ma, Yuan Zhang, Tom Dimaggio, Celeste G. Nelson, Kelly D. Stone, Alexandra F. Freeman, Liron Malki, Lucia Seminario Vidal, Latha M. Chamarthy, Valeria Briskin, Janan Mohamad, Mor Pavlovski, Jolan E. Walter, Joshua D. Milner, Eli Sprecher
Abstract
Background
Atopic dermatitis (AD) is a highly prevalent chronic inflammatory skin disease which is known to be, at least in part, genetically determined. Mutations in CARD14 have been shown to result in various forms of psoriasis and related disorders.
Objective
We aimed to identify rare DNA variants conferring a significant risk for AD through genetic and functional studies in a cohort of patients affected with severe atopic dermatitis.
Methods
Whole exome and direct gene sequencing, immunohistochemistry, real-time PCR, ELISA and functional assays in human keratinocytes were used.
Results
In a cohort of individuals referred with severe atopic dermatitis, DNA sequencing revealed in 4 patients two rare heterozygous missense mutations in CARD14 encoding the Caspase Recruitment Domain-Containing Protein 14, a major regulator of NF-κB. A dual luciferase reporter assay demonstrated that both mutations exert a dominant loss-of-function effect and result in decreased NF-κB signaling. Accordingly, immunohistochemistry staining showed decreased expression of CARD14 in patient skin as well as decreased levels of activated p65, a surrogate marker for NF-κB activity. CARD14-deficient or mutant-expressing keratinocytes displayed abnormal secretion of key mediators of innate immunity.
Conclusions
While dominant gain-of-function mutations in CARD14 are associated with psoriasis and related diseases, loss-of-function mutations in the same gene are associated with a severe variant of atopic dermatitis.
https://ift.tt/2znxgKs
Actinomycosis Presenting as Macroglossia: Case Report and Review of Literature
Abstract
Cervicofacial actinomycosis is a common form of Actinomyces infection. However, the latter seldom occurs in the tongue. We present a case of a 66 year-old man with macroglossia caused by actinomycosis of the tongue. Radiographic features were compatible with a chronic inflammatory disease. Biopsies revealed granulomas containing giant cells and Gram positive bacterial clusters consistent with actinomycosis. The patient was treated with a 22 week course of antibiotics. Imaging showed a notable improvement in the extent of the lesions 1 year later. The patient was asymptomatic and in good condition during his second year follow-up. Diagnosis of actinomycosis of the tongue can prove to be challenging because of the non-specific nature of its symptoms, clinical signs, and radiographic features. Isolation of Actinomyces sp. is an added diagnostic hurdle, because of its fastidious nature.
https://ift.tt/2QQVCmI
Exposure–response analysis and simulation of lenvatinib safety and efficacy in patients with radioiodine-refractory differentiated thyroid cancer
Abstract
Purpose
Once-daily lenvatinib 24 mg is the approved dose for radioiodine-refractory differentiated thyroid cancer. In a phase 3 trial with lenvatinib, the starting dose of 24 mg was associated with a relatively high incidence of adverse events that required dose reductions. We used an exposure–response model to investigate the risk–benefit of different dosing regimens for lenvatinib.
Methods
A population pharmacokinetics/pharmacodynamics modeling analysis was used to simulate the potential benefit of lower starting doses to retain efficacy with improved safety. The seven lenvatinib regimens tested were: 24 mg; and 20 mg, 18 mg, and 14 mg, all with or without up-titration to 24 mg. Exposure–response models for efficacy and safety were created using a 24-week time course.
Results
The approved dose of lenvatinib at 24 mg, predicted the best efficacy. However, the lenvatinib dosing regimens of 14 mg with up-titration or 18 mg without up-titration potentially provides comparable efficacy (objective response rate at 24 weeks) and a better safety profile.
Conclusions
Treatment with lenvatinib at starting doses lower than the approved once-daily 24 mg dose could provide comparable antitumor efficacy and a similar or better safety profile. Based on the results from this modeling and simulation study, a comparator dose of lenvatinib 18 mg without up-titration was selected for evaluation in a clinical trial.
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Introduction
Publication date: Available online 21 September 2018
Source: Operative Techniques in Otolaryngology-Head and Neck Surgery
Author(s): David Myssiorek
https://ift.tt/2pv3Ns8
Paradoxical case effects of psoriasis following adalimumab therapy: A case series
Dermatologic Therapy, EarlyView.
https://ift.tt/2NtDocO
The management of pseudomyogenic hemangioendothelioma of the foot: A case report and review of the literature
Dermatologic Therapy, EarlyView.
https://ift.tt/2DmnNHu
Multiple Bowen's diseases and basal cell carcinomas in a patient with acute promyelocytic leukemia treated with arsenic trioxide: A case report and effective treatment with photodynamic therapy
Dermatologic Therapy, EarlyView.
https://ift.tt/2Nw0DD6
Paradoxical case effects of psoriasis following adalimumab therapy: A case series
Dermatologic Therapy, EarlyView.
https://ift.tt/2NtDocO
The management of pseudomyogenic hemangioendothelioma of the foot: A case report and review of the literature
Dermatologic Therapy, EarlyView.
https://ift.tt/2DmnNHu
Multiple Bowen's diseases and basal cell carcinomas in a patient with acute promyelocytic leukemia treated with arsenic trioxide: A case report and effective treatment with photodynamic therapy
Dermatologic Therapy, EarlyView.
https://ift.tt/2Nw0DD6
Actinomycosis Presenting as Macroglossia: Case Report and Review of Literature
Abstract
Cervicofacial actinomycosis is a common form of Actinomyces infection. However, the latter seldom occurs in the tongue. We present a case of a 66 year-old man with macroglossia caused by actinomycosis of the tongue. Radiographic features were compatible with a chronic inflammatory disease. Biopsies revealed granulomas containing giant cells and Gram positive bacterial clusters consistent with actinomycosis. The patient was treated with a 22 week course of antibiotics. Imaging showed a notable improvement in the extent of the lesions 1 year later. The patient was asymptomatic and in good condition during his second year follow-up. Diagnosis of actinomycosis of the tongue can prove to be challenging because of the non-specific nature of its symptoms, clinical signs, and radiographic features. Isolation of Actinomyces sp. is an added diagnostic hurdle, because of its fastidious nature.
https://ift.tt/2QQVCmI
Local Delivery of Regulatory T Cells Promotes Corneal Allograft Survival
Background Regulatory T cell (Treg)-based immunotherapies have been studied as potential cell-based modalities for promoting transplant survival. However, the efficacy of local delivery of Tregs in corneal transplantation has not been fully elucidated. Herein, we investigated the kinetics of migration of subconjunctivally injected Tregs and their role in promoting corneal allograft survival. Methods GFP+CD4+CD25+Foxp3+ Tregs were isolated from draining lymph nodes (DLNs) of GFP transgenic mice and were subconjunctivally injected to corneal allograft recipients. Next, Tregs, conventional T cells (Tconv) or a combination of both was locally injected to graft recipients, and graft survival was determined by evaluating opacity scores for 10 weeks. Transplanted mice without treatment served as controls. The frequencies of MHC-II+CD11b+ antigen presenting cells (APCs), IFNγ+CD4+ Th1 cells, and CD45+ cells in the DLNs and cornea were evaluated at week 2 posttransplantation using flow cytometry. Expression of IFNγ, IL-10 and TGF-β in the grafts were assessed using RT-PCR and ELISA. Results GFP+ Tregs were detected in the ipsilateral cornea and DLNs of recipients 6 hours after injection. Subconjunctival injection of Tregs significantly decreased the frequencies of mature APCs in the graft and DLNs, suppressed Th1 frequencies in DLNs, and inhibited CD45+ cell infiltration to the graft. Finally, locally delivered Tregs significantly reduced the expression of IFN-γ, enhanced the levels of IL-10 and TGF-β in the graft, and promoted long-term allograft survival. Conclusions Our study elucidates the kinetics of migration of locally delivered Tregs and shows their role in suppressing host immune response against the allograft. * These authors contributed equally to this study. Corresponding Author: Reza Dana, M.D., M.P.H., M.Sc., Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA, Tel: +1-617-912-7401; Fax: +617-912-0117. Email: Reza_Dana@meei.harvard.edu Authorship: Chunyi Shao: Research design, performance of the research, data analysis, writing the paper Yihe Chen: Research design, performance of the research, data analysis, writing the paper Takeshi Nakao: Performance of the research Afsaneh Amouzegar: Data analysis, writing the paper Jia Yin: Performance of the research Maryam Tahvildari: Performance of the research Zala Lužnik: Performance of the research Sunil K. Chauhan: Research design, data analysis, writing the paper Reza Dana: Research design, data analysis, writing the paper Disclosure: The authors have no financial conflicts of interest. Funding: This study was supported by the National Institutes of Health/National Eye Institute Grant R01 EY012963 to RD. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2zmoVXB
https://ift.tt/2zmoVXB
Perspectives on the Optimal Genetically-Engineered pig in 2018 for Initial Clinical Trials of Kidney or Heart Xenotransplantation
For a clinical trial today, what might realistically be the optimal pig among those currently available? Deletion of expression of the 3 pig carbohydrate antigens against which humans have natural (preformed) antibodies (triple-knockout [TKO] pigs) should form the basis of any clinical trial. However, because both complement and coagulation can be activated in the absence of antibody, the expression of human complement- and coagulation-regulatory proteins is likely to be important in protecting the graft further. Any genetic manipulation that might reduce inflammation of the graft, eg, expression of hemeoxygenase-1 (HO-1) or A20, may also be beneficial to the long-term survival of the graft. The transgene for human CD47 is likely to have a suppressive effect on monocyte/macrophage and T cell activity. Furthermore, deletion of xenoantigen expression, and expression of a human complement-regulatory protein, are both associated with a reduced T cell response. Although there are several other genetic manipulations that may reduce the T cell response further, it seems likely that exogenous immunosuppressive therapy, particularly if it includes costimulation blockade, will be sufficient. We would therefore suggest that, with our present knowledge and capabilities, the optimal pig might be a TKO pig that expressed 1 or more human complement-regulatory proteins, 1 or more human coagulation-regulatory proteins, a human antiinflammatory transgene, and CD47. Absent or minimal antibody binding is important, but we suggest that the additional insertion of protective human transgenes will be beneficial, and may be essential. Address for correspondence: David K.C. Cooper MD, PhD, FRCS, ZRB 701, 1720 2nd Avenue South, University of Alabama at Birmingham, Birmingham, AL 35294, USA, Tel: (USA) 205-996-7772. E-mail: dkcooper@uabmc.edu Authorship The initial draft of the manuscript was prepared by DKCC with subsequent contributions and approval by all authors. Disclosure The authors declare no conflicts of interest. Funding Work on xenotransplantation at UAB is supported in part by NIH grant #U19 AI090959/08. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2OIs0Xa
https://ift.tt/2OIs0Xa
Early Hypertension and Diabetes after Living Kidney Donation: A National Cohort Study
Background Living kidney donors have an increased risk of end-stage renal disease, with hypertension and diabetes as the predominant causes. In this study, we sought to better understand the timeline when these diseases occur, focusing on the early postdonation period. Methods We studied 41 260 living kidney donors in the US between 2008-2014 from the SRTR and modeled incidence rates and risk factors for hypertension and diabetes. Results At 6-months, 1-year, and 2-years postdonation, there were 74, 162, and 310 cases of hypertension per 10 000 donors. Donors who were older (per 10 years, aIRR 1.40, 95% CI 1.29-1.51), male (aIRR 1.31, 95% CI 1.14-1.50), had higher BMI (per 5 units, aIRR 1.29, 95% CI 1.17-1.43), and were related to their recipient (first degree relative, aIRR 1.28, 95% CI 1.08-1.52; spouse, aIRR 1.34, 95% CI 1.08-1.66) were more likely to develop hypertension, while donors who were Hispanic/Latino were less likely (aIRR 0.71, 95% CI 0.55-0.93). At 6-months, 1-year, and 2-years, there were 2, 6, and 15 cases of diabetes per 10 000 donors. Donors who were older (per 10 years, aIRR 1.42, 95% CI 1.11-1.82), had higher BMI (per 5 units, aIRR 1.52, 95% CI 1.04-2.21), and were Hispanic/Latino (aIRR 2.45, 95% CI 1.14-5.26) were more likely to develop diabetes. Conclusions In this national study, new-onset diabetes was rare, but 3% of donors developed hypertension within 2 years of nephrectomy. These findings reaffirm that disease pathways for kidney failure differ by donor phenotype and estimate the population most at-risk for later kidney failure. Received 9 May 2018. Revision received DD MMMM YYYY. Accepted 7 August 2018. Contact Information: Dorry Segev, M.D., Ph.D. Associate Vice Chair, Department of Surgery, Johns Hopkins Medical Institutions, 2000 E. Monument St. Baltimore, MD 21205, 410-502-6115 (tel) 410-614-2079 (fax), dorry@jhmi.edu AUTHORSHIP The individual contributions of each author are as follows: • CMH designed the study, analyzed and interpreted data, drafted and revised the article, and had final approval of this version; • SB designed the study, analyzed and interpreted data, revised the article, and had final approval of this version; • AT designed the study, analyzed and interpreted data, revised the article, and had final approval of this version; • MH designed the study, revised the article, and had final approval of this version; • CEH interpreted data, revised the article, and had final approval of this version; • SD interpreted data, revised the article, and had final approval of this version; • ADM designed the study, revised the article, and had final approval of this version; • JGW designed the study, drafted and revised the article, and had final approval of this version; • ABM designed the study, interpreted data, revised the article, and had final approval of this version; • KL designed the study, revised the article, and had final approval of this version; and • DS designed the study, interpreted data, revised the article, and had final approval of this version. DISCLOSURES The authors declare no conflicts of interest. The results presented in this paper have not been published previously in whole or part, except in abstract format. FUNDING This work was supported by grant numbers F32DK109662 (Holscher), K01DK114388 (Henderson), F32DK105600 (DiBrito), K01DK101677 (Massie), K24DK101828 (Segev), and R01DK096008 (Segev) from the National Institute of Diabetes and Digestive and Kidney Diseases, grant number F32AG053025 (Haugen) from the National Institute on Aging, and by an American College of Surgeons Resident Research Scholarship (Holscher). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2zmZFjT
https://ift.tt/2zmZFjT
Cardiotrophin 1 improves kidney preservation, graft function, and survival in transplanted rats
Background Cold ischemia-reperfusion injury is unavoidable during organ transplantation, and prolonged preservation is associated with poorer function recovery. Cardiotrophin-1 (CT-1) is an IL-6 family cytokine with cytoprotective properties. This preclinical study in rats tested whether CT-1 mitigates cold renal ischemia-reperfusion injury in the context of the transplantation of long-time preserved kidneys. Methods Kidneys were flushed with cold (4°C) University of Wisconsin solution (UW) containing 0.2 μg/mL CT-1 and stored for several periods of time at 4 °C in the same solution. In a second approach, kidneys were first cold-preserved for 6 hours and then were perfused with UW containing CT-1 (0, 16, 32, or 64 μg/mL) and further cold-preserved. Organ damage markers were measured in the kidneys at the end of the storage period. For renal transplantation, recipient consanguineous Fischer rats underwent bilateral nephrectomy and received a previously cold-preserved (24 hours) kidney as described above. Survival and creatinine clearance were monitored over 30 days. Results CT-1 in perfusion and preservation fluids reduced oxidative stress markers (SOA and iNOS), inflammation markers (NF-κB and TNF-α), and vascular damage (VCAM-1) and activated LIFR and STAT-3 survival signaling. Transplantation of kidneys cold-preserved with CT-1 increased rat survival and renal function (ie, lower plasma creatinine and higher creatinine clearance) and improved kidney damage markers after transplantation (ie, lower SOA, TNF-α, ICAM-1, and VCAM-1 and higher NF-κB). Conclusions CT-1 represents a novel therapeutic strategy to reduce ischemia-reperfusion and cold preservation injury, to rescue suboptimal kidneys and, consequently, to improve the clinical outcomes of renal transplantation. Received 13 January 2018. Revision received 30 April 2018. Accepted 24 May 2018. *These authors share first authorship. Correspondence: José M. Lopez-Novoa, Department of Physiology and Pharmacology, University of Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007 Salamanca, Spain. E-mail: jmlnovoa@usal.es. Fax number: +34 923294669 AUTHORSHIP PAGE 1. Authorship: BG-C, VB-G, JML-N, and FJL-H participated in the research design and writing of the paper. BG-C, VB-G, DL-M, and JRSG-R participated in the performance of the research. BG-C, VB-G, JML-N, and FJL-H participated in the data analysis. 2. Disclosure: The authors have no conflicts of interest to declare. 3. Funding: This study was supported by funds from Digna Biotech, Instituto de Salud Carlos III (grants DT15S/00166 and PI15/01055), and the European Commission (FEDER). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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https://ift.tt/2OJ4FV6
The selective RNA polymerase I inhibitor CX-5461 mitigates neointimal remodeling in a modified model of rat aortic transplantation
Background Transplant vasculopathy is a major cause of chronic rejection of transplanted organs. In the present study, we examined the effects of CX-5461, a novel selective inhibitor of RNA polymerase I, on development of transplant vasculopathy using a modified model of rat aortic transplantation. Methods The thoracic aortas from Fischer rats were transplanted into the abdominal cavity of Lewis rats. CX-5461 was mixed in pluronic gel and administered via peri-vascular release. Results Treatment with CX-5461 mitigated the development of neointimal hyperplasia and vascular inflammation. This effect was likely to be attributable in part to inhibition of macrophage-dependent innate immunity reactions. Specifically, CX-5461 exhibited potent inhibitory effects on macrophage migration and lipopolysaccharide-induced activation. Treatment with CX-5461 also prevented macrophage differentiation and maturation from primary bone marrow cells. In macrophages, CX-5461 did not alter the total amount of p53 protein, but significantly increased p53 phosphorylation, which was involved in regulating cytokine-stimulated macrophage proliferation. Conclusions In conclusion, our results suggest that pharmacological inhibition of Pol I may be a novel strategy to treat transplantation-induced arterial remodeling. Received 11 January 2018. Revision received 27 June 2018. Accepted 29 June 2018. These authors contributed equally to the work, Chaochao Dai, MBBS, Mengyao Sun. Address correspondence to: Dr. Fan Jiang (fjiang@sdu.edu.cn) or Dr. Jianli Wang (wangmaq@sdu.edu.cn), School of Basic Medicine, Shandong University, 44 Wen Hua Xi Road, Jinan, Shandong Province 250012, China. Phone: +86 531 8838 2044; Fax +86 531 8295 9051 Conflict of interest declaration: none Author contributions: Chaochao Dai: performed experiments; did data acquisition and analysis; involved in drafting the manuscript Mengyao Sun: performed experiments; did data acquisition and analysis; involved in drafting the manuscript Fengjiao Wang: performed experiments and data acquisition/analysis Jiankang Zhu: performed experiments and data acquisition/analysis Yaping Wei: performed experiments and data acquisition/analysis Xiaotong Guo: performed experiments and data acquisition/analysis Siqin Ma: participated in data acquisition and analysis Bo Dong: participated in data acquisition and analysis Gejin Wang: participated in data acquisition and analysis Fan Jiang: conceived the study; provided intellectual inputs for data interpretations; revised the manuscript Jianli Wang: conceived the study; provided intellectual inputs for data interpretations Funding support This study was supported by grants from Natural Science Foundation of China (91539102 and 31471087 for F.J.; 81500496 for J.Z.), National 973 Basic Research Program (2010CB732605 for F.J.), Natural Science Foundation of Shandong Province (No. ZR2016HM24 for J.W.) and University Innovation Fund of Jinan City (201401251 for J.W.). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2znIQ8i
https://ift.tt/2znIQ8i
Socioeconomic Status and Kidney Transplant Outcomes in a Universal Healthcare System: A Population-based Cohort Study
Background Conflicting evidence exists regarding the relationship between socioeconomic status (SES) and outcomes following kidney transplantation. Methods We conducted a population-based cohort study in a publicly funded healthcare system using linked administrative healthcare databases from Ontario, Canada to assess the relationship between SES and total graft failure (ie, return to chronic dialysis, preemptive retransplantation, or death) in individuals who received their first kidney transplant between 2004 and 2014. Secondary outcomes included death-censored graft failure, death with a functioning graft, all-cause mortality and all-cause hospitalization (post hoc outcome). Results 4414 kidney transplant recipients were included (median age, 53 years; 36.5% female) and the median (25th, 75th percentile) follow-up was 4.3 (2.1, 7.1) years. In an unadjusted Cox proportional hazards model, each $10 000 increase in neighborhood median income was associated with an 8% decline in the rate of total graft failure (hazard ratio 0.92 [95% confidence interval [CI]: 0.87, 0.97]). After adjusting for recipient, donor and transplant characteristics, SES was not significantly associated with total or death-censored graft failure. However, each $10 000 increase in neighborhood median income remained associated with a decline in the rate of death with a functioning graft (aHR 0.91, 95% CI: 0.83, 0.98), all-cause mortality (aHR 0.92, 95% CI: 0.86, 0.99) and all-cause hospitalization (aHR 0.95, 95% CI: 0.92, 0.98). Conclusions In conclusion, in a universal healthcare system, SES may not adversely influence graft health but SES gradients may negatively impact other kidney transplant outcomes and could be used to identify patients at increased risk of death or hospitalization. These authors contributed equally to this work. Kyla L. Naylor PhD, Gregory A. Knoll MD, MSc. Correspondence: S. Joseph Kim, MD, PhD, MHS, FRCPC, Toronto General Hospital, 585 University Avenue, 11-PMB-129, Toronto, Ontario, Canada, M5G 2N2, Phone: 416-340-3228, Fax: 416-340-4701, Email: joseph.kim@uhn.ca Author Contributions: S.J.K conceived of the study. S.Z.S and E.M provided analytic and statistical support. K.L.N drafted the manuscript. All authors read and approved the final manuscript. Disclosures: Drs. Kim and Knoll have received investigator-initiated research grants from Canadian Institutes of Health Research and Astellas Canada. Dr. Garg received an investigator-initiated grant from Astellas for a Canadian Institutes of Health Research study in living kidney donors. Dr. Amit Garg was supported by the Dr. Adam Linton Chair in Kidney Health Analytics, and a Clinician Investigator Award from the Canadian Institutes of Health Research. Others: None to declare. Funding: Kidney Foundation of Canada (KFOC110009) Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2OIVN1X
https://ift.tt/2OIVN1X
Plaque‐like dermatofibroma with satellitosis in a young woman
International Journal of Dermatology, EarlyView.
https://ift.tt/2znkJXC
The cake flap: a technique of serial excision in quadrants useful beyond congenital nevi
International Journal of Dermatology, EarlyView.
https://ift.tt/2OK0oke
Relative abundance of nasal microbiota in chronic rhinosinusitis by structured histopathology
International Forum of Allergy &Rhinology, EarlyView.
https://ift.tt/2OJHQkn
A novel de novo mutation p.Ala428Asp in KRT5 gene as a cause of localized epidermolysis bullosa simplex
Experimental Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2QRA35f
Effect of oral isotretinoin on the nucleo‐cytoplasmic distribution of FoxO1 and FoxO3 proteins in sebaceous glands of patients with acne vulgaris
Experimental Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2xHV7Cz
The Eczema Solution. Sue Armstrong‐Brown. London: Vermilion, 2002; 128 pp. ISBN: 978‐009188284. Price £12.99.
British Journal of Dermatology, EarlyView.
https://ift.tt/2Dobyu2
Clinical, dermoscopic and reflectance confocal microscopy characterization of facial basal cell carcinomas presenting as small white lesions on sun‐damaged skin
British Journal of Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2NwwrI8
The Eczema Solution. Sue Armstrong‐Brown. London: Vermilion, 2002; 128 pp. ISBN: 978‐009188284. Price £12.99.
British Journal of Dermatology, EarlyView.
https://ift.tt/2Dobyu2
Clinical, dermoscopic and reflectance confocal microscopy characterization of facial basal cell carcinomas presenting as small white lesions on sun‐damaged skin
British Journal of Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2NwwrI8
Ingenol mebutate versus imiquimod versus diclofenac for actinic cheilitis: a 6‐month follow‐up clinical study
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2PXtsoK
Development of pemphigoid nodularis after remission of bullous lesions
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2O7v5mI
Successful treatment with dapsone for lupus profundus accompanied by xanthomatous reaction
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2PWleNv
The histological absence of IgG4 positive plasma cells in juvenile xanthogranuloma; comments on ‘Systemic juvenile xanthogranuloma: a case report and brief review’
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2O7v428
The controversy of complete lymph node dissection; reply to ‘Completion lymphadenectomy should not necessarily be recommended after a positive SLN biopsy’
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2PYA72a
Ingenol mebutate versus imiquimod versus diclofenac for actinic cheilitis: a 6‐month follow‐up clinical study
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2PXtsoK
Development of pemphigoid nodularis after remission of bullous lesions
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2O7v5mI
Successful treatment with dapsone for lupus profundus accompanied by xanthomatous reaction
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2PWleNv
The histological absence of IgG4 positive plasma cells in juvenile xanthogranuloma; comments on ‘Systemic juvenile xanthogranuloma: a case report and brief review’
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2O7v428
The controversy of complete lymph node dissection; reply to ‘Completion lymphadenectomy should not necessarily be recommended after a positive SLN biopsy’
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2PYA72a
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