A gyógyszer indukálta vérzékeny betegek fogorvosi, szájsebészeti ellátása: a 2015-ös hazai szakmai ajánlás alkalmazása és értékelése

Absztrakt Bevezetés: A Magyar Arc-, Állcsont- és Szájsebészeti Társaság és a Magyar Fogorvosok Implantológiai Társasága által 2015-ben elfogadásra került „A gyógyszer indukálta vérzékeny betegek fogorvosi ellátása” szakmai ajánlás. Célkitűzés: A szerzők célja volt az ajánlásban leírt lokális vérzéscsillapítási módszerek hatékonyságának, megbízhatóságának ellenőrzése. Módszer: Az orális antithromboticus kezelésben részesülő betegeiknél vizsgálták a fogorvosi, szájsebészeti ellátásukat követő utóvérzések előfordulását, retrospektív módon. Eredmények: 263, vérzéssel járó beavatkozás történt (186 betegnél), amelyből 138 K-vitamin-antagonista, 97 thrombocytaaggregáció-gátló és 6, úgynevezett új típusú orális antikoaguláns kezelésben részesülő betegeknél. Összesen 6 (2,3%) esetben tapasztaltak utóvérzést az egyórás kontrollnál, míg ügyeletbe 1 beteg jött vissza utóvérzés miatt (0,5%). Ezzel szemben 86-an jelentkeztek ügyeletükön, akiknél az ajánlást nem vették figyelembe, közülük K-vitamin-antagonista gyógyszert szedett 3 beteg, alacsony molekulasúlyú heparinkezelésben részesült 24 beteg, thrombocytaaggregáció-gátló szert szedett 30 beteg és új típusú orális antikoaguláns kezelésben részesült 1 beteg. Következtetések: A hazai szakmai ajánlás az ambuláns gyakorlatban biztonságosan alkalmazható az antithromboticus terápiában részesülő páciensek vérzéssel járó fogorvosi/szájsebészeti beavatkozásakor, habár a körzetes fogorvos ellátók sok esetben nincsenek ilyen jellegű ellátásra felkészülve. Orv. Hetil., 2016, 157(43), 1722–1728. | Abstract Introduction: In 2015 a new Hungarian guideline was published regarding dental treatment and management of anticoagulated patients in agreement of the Hungarian Association of Oral and Maxillofacial Surgeons and the Dental Implantology Association of Hungarian Dentists. Aim: The aim of the authors was to evaluate the efficiency and safety of local hemostatic measures recommended by the guideline in anticoagulated patients. Method: In these patients, postoperative bleeding episodes were examined after dental and oral surgical treatments, retrospectively. Results: Overall 263 bleeding risk cases were treated; 138 patients with vitamin K antagonists, 97 patients with antiplatelet therapy and 6 patients with novel oral anticoagulants. Six patients (2.3%) had minor postoperative bleeding after the “one hour control”, while one patient needed a night duty support (0.5%). In contrast, 86 patients who were treated in rural practices neglecting the guideline attended the night duty with postoperative bleeding (3 patients treated with vitamin K antagonists, 24 patients taking low molecular weight heparin, 30 patients receiving antiplatelet therapy and one patient on novel oral anticoagulant therapy. Conclusions: The Hungarian guideline can be applied safely, without increasing the risk of postoperative bleeding, however, rural dental practices are frequently unprepared for these treatments. Orv. hetil., 2016, 157(43), 1722–1728

Human Bullous Pemphigoid Antigen 2 Transgenic Skin Elicits Specific IgG in Wild-Type Mice

Bullous pemphigoid antigen 2 (BPAG2) is targeted by autoantibodies in patients with bullous pemphigoid (BP), and absent in patients with one type of epidermolysis bullosa (OMIM #226650). A keratin 14 promoter construct was used to produce transgenic (Tg) mice appropriately expressing human BPAG2 (hBPAG2) in murine epidermal basement membrane (BM). Grafts of Tg skin placed on gender-matched, syngeneic wild type (Wt) or major histocompatibility complex I (MHC I)−/− mice elicited IgG that bound human epidermal BM and BPAG2. Production of such IgG in grafted mice was prompt (detectable within 16±2 days), robust (titer ≥1,280), durable (present ≥380 days), and correlated with the involution and loss of Tg skin grafts. MHC II−/− mice grafted with Tg skin did not develop anti-hBPAG2 IgG or graft loss indicating that MHC II:CD4+ T cell interactions were crucial for these responses. Tg skin grafts on Wt mice developed neutrophil-rich infiltrates, dermal edema, subepidermal blisters, and deposits of immunoreactants in epidermal BM. This model shows fidelity to alterations seen in patients with BP, has relevance to immune responses that may arise in patients with epidermolysis bullosa following BPAG2 gene replacement, and can be used to identify interventions that may block production of IgG against proteins in epidermal BM

A Simple Method for Sample Preparation to Facilitate Efficient Whole-Genome Sequencing of African Swine Fever Virus

In the recent years, African swine fever has become the biggest animal health threat to the swine industry. To facilitate quick genetic analysis of its causative agent, the African swine fever virus (ASFV), we developed a simple and efficient method for next generation sequencing of the viral DNA. Execution of the protocol does not demand complicated virus purification steps, enrichment of the virus by ultracentrifugation or of the viral DNA by ASFV-specific PCRs, and minimizes the use of Sanger sequencing. Efficient DNA-se treatment, monitoring of sample preparation by qPCR, and whole genome amplification are the key elements of the method. Through detailed description of sequencing of the first Hungarian ASFV isolate (ASFV_HU_2018), we specify the sensitive steps and supply key reference numbers to assist reproducibility and to facilitate the successful use of the method for other ASFV researchers

Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary

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Painful skin lesions and squamous cell carcinoma predict overall mortality risk in organ transplant recipients:a cohort study

Item does not contain fulltextBACKGROUND: Organ transplant recipients (OTRs) have a highly increased risk of cutaneous squamous cell carcinomas (SCCs). Sensation of pain in cutaneous tumours is a powerful patient-reported warning signal for invasive SCCs in OTRs. OBJECTIVES: To investigate the impact of painful vs. painless skin lesions and SCC vs. other skin lesions on the overall mortality risk in OTRs. METHODS: We followed 410 OTRs from 10 different centres across Europe and North America between 2008 and 2015. These patients had been enrolled in an earlier study to define clinically meaningful patient-reported warning signals predicting the presence of SCC, and had been included if they had a lesion requiring histological diagnosis. Cumulative incidences of overall mortality were calculated using Kaplan-Meier survival analysis, and risk factors were analysed with Cox proportional hazard analysis. RESULTS: There was an increased overall mortality risk in OTRs who reported painful vs. painless skin lesions, with a hazard ratio (HR) of 1.6 [95% confidence interval (CI) 0.97-2.7], adjusted for age, sex and other relevant factors. There was also an increased overall mortality risk in OTRs diagnosed with SCC compared with other skin lesions, with an adjusted HR of 1.7 (95% CI 1.0-2.8). Mortality due to internal malignancies and systemic infections appeared to prevail in OTRs with SCC. CONCLUSIONS: We suggest that OTRs have an increased overall mortality risk if they develop painful skin lesions or are diagnosed with cutaneous SCC

Selective Impairment of TH17-Differentiation and Protection against Autoimmune Arthritis after Overexpression of BCL2A1 in T Lymphocytes

The inhibition of apoptotic cell death in T cells through the dysregulated expression of BCL2 family members has been associated with the protection against the development of different autoimmune diseases. However, multiple mechanisms were proposed to be responsible for such protective effect. The purpose of this study was to explore the effect of the Tcell overexpression of BCL2A1, an anti-apoptotic BCL2 family member without an effect on cell cycle progression, in the development of collagen-induced arthritis. Our results demonstrated an attenuated development of arthritis in these transgenic mice. The protective effect was unrelated to the suppressive activity of regulatory T cells but it was associated with a defective activation of p38 mitogen-activated protein kinase in CD4+ cells after in vitro TCR stimulation. In addition, the in vitro and in vivo TH17 differentiation were impaired in BCL2A1 transgenic mice. Taken together, we demonstrated here a previously unknown role for BCL2A1 controlling the activation of CD4+ cells and their differentiation into pathogenic proinflammatory TH17 cells and identified BCL2A1 as a potential target in the control of autoimmune/inflammatory diseases

DNA methylation profiles delineate epigenetic heterogeneity in seminoma and non-seminoma

Background: It remains important to understand the biology and identify biomarkers for less studied cancers like testicular cancer. The purpose of this study was to determine the methylation frequency of several cancer-related genes in different histological types of testicular cancer and normal testis tissues (NT). Methods: DNA was isolated from 43 seminomas (SEs), 14 non-SEs (NSEs) and 23 NT, and was assayed for promoter methylation status of 15 genes by quantitative methylation-specific PCR. The methylation status was evaluated for an association with cancer, and between SEs and NSEs. Results: We found differential methylation pattern in SEs and NSEs. MGMT, VGF, ER-Β and FKBP4 were predominately methylated in NSEs compared with SEs. APC and hMLH1 are shown to be significantly more methylated in both subtypes in comparison with NT. When combining APC, hMLH1, ER-Β and FKBP4, it is possible to identify 86% of the NSEs, whereas only 7% of the SEs. Conclusions: Our results indicate that the methylation profile of cancer-associated genes in testicular cancer correlates with histological types and show cancer-specific pattern for certain genes. Further methylation analysis, in a larger cohort is needed to elucidate their role in testicular cancer development and potential for therapy, early detection and disease monitoring

Nonadhesive Culture System as a Model of Rapid Sphere Formation with Cancer Stem Cell Properties

BACKGROUND: Cancer stem cells (CSCs) play an important role in tumor initiation, progression, and metastasis and are responsible for high therapeutic failure rates. Identification and characterization of CSC are crucial for facilitating the monitoring, therapy, or prevention of cancer. Great efforts have been paid to develop a more effective methodology. Nevertheless, the ideal model for CSC research is still evolving. In this study, we created a nonadhesive culture system to enrich CSCs from human oral squamous cell carcinoma cell lines with sphere formation and to characterize their CSC properties further. METHODS: A nonadhesive culture system was designed to generate spheres from the SAS and OECM-1 cell lines. A subsequent investigation of their CSC properties, including stemness, self-renewal, and chemo- and radioresistance in vitro, as well as tumor initiation capacity in vivo, was also performed. RESULTS: Spheres were formed cost-effectively and time-efficiently within 5 to 7 days. Moreover, we proved that these spheres expressed putative stem cell markers and exhibited chemoradiotherapeutic resistance, in addition to tumor-initiating and self-renewal capabilities. CONCLUSIONS: Using this nonadhesive culture system, we successfully established a rapid and cost-effective model that exhibits the characteristics of CSCs and can be used in cancer research

A COL17A1 Splice-Altering Mutation Is Prevalent in Inherited Recurrent Corneal Erosions

PurposeCorneal dystrophies are a genetically heterogeneous group of disorders. We previously described a family with an autosomal dominant epithelial recurrent erosion dystrophy (ERED). We aimed to identify the underlying genetic cause of ERED in this family and 3 additional ERED families. We sought to characterize the potential function of the candidate genes using the human and zebrafish cornea.DesignCase series study of 4 white families with a similar ERED. An experimental study was performed on human and zebrafish tissue to examine the putative biological function of candidate genes.ParticipantsFour ERED families, including 28 affected and 17 unaffected individuals.MethodsHumanLinkage-12 arrays (Illumina, San Diego, CA) were used to genotype 17 family members. Next-generation exome sequencing was performed on an uncle–niece pair. Segregation of potential causative mutations was confirmed using Sanger sequencing. Protein expression was determined using immunohistochemistry in human and zebrafish cornea. Gene expression in zebrafish was assessed using whole-mount in situ hybridization. Morpholino-induced transient gene knockdown was performed in zebrafish embryos.Main Outcome MeasuresLinkage microarray, exome analysis, DNA sequence analysis, immunohistochemistry, in situ hybridization, and morpholino-induced genetic knockdown results.ResultsLinkage microarray analysis identified a candidate region on chromosome chr10:12,576,562–112,763,135, and exploration of exome sequencing data identified 8 putative pathogenic variants in this linkage region. Two variants segregated in 06NZ–TRB1 with ERED: COL17A1 c.3156C→T and DNAJC9 c.334G→A. The COL17A1 c.3156C→T variant segregated in all 4 ERED families. We showed biologically relevant expression of these proteins in human cornea. Both proteins are expressed in the cornea of zebrafish embryos and adults. Zebrafish lacking Col17a1a and Dnajc9 during development show no gross corneal phenotype.ConclusionsThe COL17A1 c.3156C→T variant is the likely causative mutation in our recurrent corneal erosion families, and its presence in 4 independent families suggests that it is prevalent in ERED. This same COL17A1 c.3156C→T variant recently was identified in a separate pedigree with ERED. Our study expands the phenotypic spectrum of COL17A1 disease from autosomal recessive epidermolysis bullosa to autosomal dominant ERED and identifies COL17A1 as a key protein in maintaining integrity of the corneal epithelium