RESUMEN
This study aimed to investigate adhesive shear bond strength (SBS) on an ultrafine-grained niobium alloy (UFG-Nb) that is a potential dental implant material. SBS of three adhesive systems combined with three composites to UFG-Nb was compared to corresponding SBS to Ti-6Al-4V and to zirconia. Specimens of the substrates UFG-Nb, Ti-6Al-4V and zirconia with plane surfaces were sandblasted with Al2O3, cleaned and dried. Three adhesive systems (Futurabond U, Futurabond M + , Futurabond M + DCA; all VOCO GmbH, Cuxhaven, Germany) were applied each on specimens of each substrate and light cured. One composite (BifixSE, BifixQM, GrandioSO; all VOCO GmbH) was applied and light cured resulting in 27 groups (n = 10) for all substrate-adhesive-composite-combinations. SBS was measured after 24 h of storage. To simulate aging equally prepared specimens underwent 5000 thermocycles before SBS measurement. There was no significant difference in SBS within the non-aged groups. Among the artificially aged groups, GrandioSO-groups showed a greater variance of SBS than the other composites. All significant differences of corresponding UFG-Nb-, Ti-6Al-4V- and zirconia-groups with same adhesive-composite-combination (ACC) were observed between UFG-Nb and zirconia or Ti-6Al-4V and zirconia but never between the two metallic substrates. The similarity between these materials might show in their adhesive bonding behavior. As there were no differences comparing corresponding groups prior to and after artificial aging, it can be concluded that aging does not affect SBS to UFG-Nb, Ti-6Al-4V and zirconia using the tested ACCs. Adhesive bonding of established ACCs to UFG-Nb is possible resulting in SBS comparable to those on Ti-6Al-4V and zirconia surfaces.
Asunto(s)
Aleaciones , Cementos Dentales , Ensayo de Materiales , Niobio , Resistencia al Corte , Propiedades de Superficie , Titanio , Circonio , Niobio/química , Circonio/química , Aleaciones/química , Titanio/química , Cementos Dentales/química , Implantes Dentales , Recubrimiento Dental Adhesivo/métodos , Materiales Dentales/química , Aleaciones Dentales/química , Análisis del Estrés Dental , Estrés Mecánico , Cementos de Resina/química , Resinas Compuestas/químicaRESUMEN
Neurinomas in the nose and the nasal sinuses are rare. In the present work, we present an exceedingly rare case of a disfiguring neurinoma involving the nasal columella. Treatment of choice is complete resection of the tumor. For an optimal view for tumor resection and esthetic and functional reconstruction, we recommend an open surgical approach.
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Neurilemoma , Nariz , Rinoplastia , Cóclea , Estética , Humanos , Tabique Nasal , Neurilemoma/diagnóstico , Neurilemoma/cirugía , Nariz/patología , Nariz/cirugíaRESUMEN
BACKGROUND: The use of UV-emitting tanning devices for cosmetic purposes is associated with an increased risk of melanoma and non-melanoma skin cancer. Young women are the most frequent users, therefore, there is an increasing concern about the regulation of sunbed use. OBJECTIVE: The primary objective is to assess the current legislation on sunbed use among European countries. METHODS: We developed a 30-item questionnaire to gather the most relevant information about sunbed use legislation. The questionnaire was sent to Euromelanoma coordinators and to designated coordinators out of the Euromelanoma network. RESULTS: We obtained a response rate of 64%. More than 25% of the countries did not report any specific legislation. Roughly one-third of the countries does not have a restriction for minors. Even in countries with a specific legislation, a lack or insufficient enforcement of age limit was observed in up to 100% of the inspections based on the PROSAFE report from 2012. Self-tanning devices were reported in 50%, and almost 40% of countries do not require supervision of use. Although a warning display is required in 77% of cases, a signed informed consent is not required in 80%. In the vast majority of cases, the number of licensed or closed tanning centres is unknown. CONCLUSIONS: Despite the evidence of its harmful effects, and its frequent use by young people, many of whom are at high risk of skin cancer because of fair skin, a significant number of European countries lack a specific legislation on tanning devices. In order to limit the access of young people to sunbeds, a more strictly enforced regulation is needed, as well as regulation regarding advertisement, and location of tanning centres, in addition to health promotion campaigns that target the vulnerable population of young women seeking its use for improved cosmesis.
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Industria de la Belleza/instrumentación , Industria de la Belleza/legislación & jurisprudencia , Menores/legislación & jurisprudencia , Neoplasias Cutáneas/prevención & control , Baño de Sol/legislación & jurisprudencia , Adolescente , Publicidad/legislación & jurisprudencia , Niño , Europa (Continente) , Humanos , Aplicación de la Ley , Encuestas y Cuestionarios , Rayos Ultravioleta/efectos adversosRESUMEN
BACKGROUND: Psoriasiform and eczematous eruptions are the most common dermatological adverse reactions linked to anti-tumour necrosis factor (TNF)-α therapy. Yet, a detailed characterization of their immune phenotype is lacking. OBJECTIVES: To characterize anti-TNF-α-induced inflammatory skin lesions at a histopathological, cellular and molecular level, compared with psoriasis, eczema (atopic dermatitis) and healthy control skin. METHODS: Histopathological evaluation, gene expression (quantitative real-time polymerase chain reaction) and computer-assisted immunohistological studies (TissueFAXS) were performed on 19 skin biopsies from patients with inflammatory bowel disease (n = 17) and rheumatoid arthritis (n = 2) with new-onset inflammatory skin lesions during anti-TNF-α-therapy. RESULTS: Although most biopsies showed a psoriasiform and/or spongiotic (eczematous) histopathological architecture, these lesions were inconsistent with either psoriasis or eczema on a molecular level using an established chemokine (C-C motif) ligand 27/inducible nitric oxide synthase classifier. Despite some differences in immune skewing depending on the specific histopathological reaction pattern, all anti-TNF-α-induced lesions showed strong interferon (IFN)-γ activation, at higher levels than in psoriasis or eczema. IFN-γ was most likely produced by CD3/CD4/Tbet-positive T helper 1 lymphocytes. CONCLUSIONS: New-onset anti-TNF-α-induced eruptions previously classified as psoriasis or spongiotic dermatitis (eczema) exhibit a molecular profile that is different from either of these disorders.
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Erupciones por Medicamentos/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/efectos adversos , Adulto , Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Biopsia , Citocinas/metabolismo , Eccema/inmunología , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/efectos adversos , Interferón gamma/metabolismo , Células Asesinas Naturales/inmunología , Psoriasis/inmunología , Dermatosis del Cuero Cabelludo/inmunología , Linfocitos T Citotóxicos/inmunología , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
BACKGROUND: High-intensity noise exposure from impulse and blast noise events often leads to acute hearing loss and may cause irreversible permanent hearing loss as a long-term consequence. Here, a treatment regime was developed to limit permanent damage based on a preclinical animal model of acute noise trauma. AIM: To develop clinical trials for the treatment of acute noise traumas using approved drugs. The otoprotective potential of glucocorticoids applied locally to the inner ear was examined. MATERIALS AND METHODS: A series of experiments with different impulse noise exposures were performed. Permanent hearing loss and hair cell density were assessed 14 days after exposure. Hearing and hair cell preservation were investigated as a function of the glucocorticoid dose. RESULTS: After impulse noise exposure, local application to the round window of the cochlea of high-dose prednisolone (25 mg/ml) or methylprednisolone (12.5 mg/ml) resulted in a statistically significant reduction in hearing loss compared with the control group. CONCLUSION: The local application of high doses of the drugs to the round window of the cochlea appears to be an effective treatment for acute noise trauma.
Asunto(s)
Percepción Auditiva/efectos de los fármacos , Oído Interno/efectos de los fármacos , Oído Interno/fisiopatología , Glucocorticoides/administración & dosificación , Pérdida Auditiva Provocada por Ruido/tratamiento farmacológico , Pérdida Auditiva Provocada por Ruido/fisiopatología , Administración Tópica , Animales , Enfermedad Crónica , Cobayas , Pérdida Auditiva Provocada por Ruido/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Lipocalin 2 (Lcn2) is rapidly produced by damaged nephron epithelia and is one of the most promising new markers of renal injury, delayed graft function and acute allograft rejection (AR); however, the functional importance of Lcn2 in renal transplantation is largely unknown. To understand the role of Lcn2 in renal AR, kidneys from Balb/c mice were transplanted into C57Bl/6 mice and vice versa and analyzed for morphological and physiological outcomes of AR at posttransplantation days 3, 5, and 7. The allografts showed a steady increase in intensity of interstitial infiltration, tubulitis and periarterial aggregation of lymphocytes associated with a substantial elevation in serum levels of creatinine, urea and Lcn2. Perioperative administration of recombinant Lcn2:siderophore:Fe complex (rLcn2) to recipients resulted in functional and morphological amelioration of the allograft at day 7 almost as efficiently as daily immunosuppression with cyclosporine A (CsA). No significant differences were observed in various donor-recipient combinations (C57Bl/6 wild-type and Lcn2(-/-) , Balb/c donors and recipients). Histochemical analyses of the allografts showed reduced cell death in recipients treated with rLcn2 or CsA. These results demonstrate that Lcn2 plays an important role in reducing the extent of kidney AR and indicate the therapeutic potential of Lcn2 in transplantation.
Asunto(s)
Funcionamiento Retardado del Injerto/prevención & control , Rechazo de Injerto/prevención & control , Trasplante de Riñón , Lipocalina 2/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Enfermedad Aguda , Animales , Femenino , Rechazo de Injerto/etiología , Rechazo de Injerto/metabolismo , Supervivencia de Injerto/fisiología , Inmunosupresores/uso terapéutico , Lipocalina 2/fisiología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Animales , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Trasplante HomólogoRESUMEN
Biodegradable and biocompatible magnesium alloys appear to be very promising not only for temporary clinical application but also for developing deformable and degradable medical implants. This study analyzes the in vivo degradation behavior and the impact on the paranasal sinuses of the highly ductile Mg-2 wt%Nd alloy (MgNd2) in order to provide a basis for a satisfying stent system for the therapy of a chronic sinusitis. Moreover, in vitro tests were carried out on primary porcine nasal epithelial cells (PNEC). For the in vivo tests, cylindrical MgNd2 specimens were implanted into the sinus' mucosa of minipigs. During and after a total period of 180 days the long-term biodegradation and biocompatibility properties after direct contact with the physiological tissue were analyzed. Biodegradation was investigated by measuring the mass and volume losses of the MgNd2 specimens as well as by performing element analyses to obtain information about the degradation layer. The influence on the surrounding tissue of paranasal sinuses was evaluated by endoscopic and histopathological examinations of the mucosa. Here, only a locally unspecific chronic infection was found. The degradation rate showed a maximum after 45 days postsurgery and was determined to decrease subsequently. In vitro experiments using PNEC showed adequate biocompatibility of MgNd2. This study demonstrates a good in vivo biocompatibility for MgNd2 in the system of paranasal sinuses and underlines the promising properties of alloy MgNd2 for biodegradable nasal stent applications.
Asunto(s)
Aleaciones/farmacología , Ensayo de Materiales/métodos , Mucosa Nasal/efectos de los fármacos , Aleaciones/efectos adversos , Animales , Materiales Biocompatibles/efectos adversos , Materiales Biocompatibles/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Corrosión , Endoscopía , Seno Frontal/efectos de los fármacos , Seno Frontal/metabolismo , Seno Frontal/patología , Seno Frontal/ultraestructura , Inflamación/inducido químicamente , Inflamación/metabolismo , Mucosa Nasal/citología , Mucosa Nasal/fisiología , Mucosa Nasal/ultraestructura , Porcinos , Porcinos EnanosRESUMEN
The frontal sinus recess consists of anatomically narrow passages that are prone to stenosis in endonasal frontal sinus surgery for chronic sinus disease. Over the past 100 years, diverse frontal sinus stents have been developed and evaluated in clinical and animal studies. However, superinfection, formation of granulations tissue, stent dislocation and late stenosis of the duct have remained challenges and subject of debate in the literature. Currently developed biodegradable materials, including rare earth-containing magnesium alloys are promising candidates for application as temporary implant materials. The Mg 2 % wt Nd alloy (MgNd2) was used to design a nasal stent that fit the porcine anatomy. In the current study, we evaluate biocompatibility, biodegradation and functionality of a frontal sinus stent in 16 minipigs over 6 months. Intraoperative endoscopy revealed free stent lumen in all cases. Blood examination and clinical examinations indicated no systematic or local inflammation signs. The histopathology and elements analysis showed a very good biocompatibility. The µ-computed tomography-based volumetric analysis showed substantial stent degradation within 6 months. Our MgNd2 based stent appears to be a promising, solid basis for the development of a frontal sinus stent for clinical use.
Asunto(s)
Implantes Absorbibles , Aleaciones , Seno Frontal/cirugía , Magnesio , Stents , Animales , Seno Frontal/diagnóstico por imagen , Modelos Animales , Porcinos , Porcinos EnanosRESUMEN
BACKGROUND: High-intensity noise exposure from impulse and blast noise events often leads to acute hearing loss and may cause irreversible permanent hearing loss as a long-term consequence. Here, a treatment regime was developed to limit permanent damage based on a preclinical animal model of acute noise trauma. AIM: To develop clinical trials for the treatment of acute noise traumas using approved drugs. The otoprotective potential of glucocorticoids applied locally to the inner ear was examined. MATERIALS AND METHODS: A series of experiments with different impulse noise exposures was performed. Permanent hearing loss and hair cell density were assessed 14 days after exposure. Hearing and hair cell preservation were investigated as a function of glucocorticoid dose. RESULTS: After impulse noise exposure, local application of high-dose prednisolone (25 mg/ml) or methylprednisolone (12.5 mg/ml) to the round window of the cochlea resulted in a statistically significant reduction in hearing loss compared to the control group. CONCLUSION: Local application of high doses of the drugs to the round window of the cochlea appears to be an effective treatment for acute noise trauma.
Asunto(s)
Glucocorticoides/administración & dosificación , Pérdida Auditiva Provocada por Ruido/tratamiento farmacológico , Pérdida Auditiva Provocada por Ruido/fisiopatología , Ventana Redonda/efectos de los fármacos , Administración Tópica , Animales , Relación Dosis-Respuesta a Droga , Cobayas , Pérdida Auditiva Provocada por Ruido/diagnóstico , Resultado del TratamientoRESUMEN
Tissue from endometrial diagnostic curettage material may show small clumps of stromal cells, which are pushed together (stromal collapse) and present a picture of glandular and stromal breakdown. This can be misinterpreted as small cell structured carcinoma, possibly of neuroendocrine or basal cell origin. Immunohistochemical investigations (e.g. estrogen receptor, epithelial and neuroendocrine markers and proliferation markers) are helpful in identifying the correct differential diagnosis.
Asunto(s)
Neoplasias Endometriales/patología , Endometrio/patología , Células del Estroma/patología , Anciano de 80 o más Años , Artefactos , Biomarcadores de Tumor/análisis , Carcinoma Basocelular/patología , Carcinoma Neuroendocrino/patología , Transformación Celular Neoplásica/patología , Cuello del Útero/patología , Diagnóstico Diferencial , Dilatación y Legrado Uterino , Femenino , Humanos , InmunohistoquímicaRESUMEN
Deep-seated lipomatous tumors of the peripheral soft tissue of the extremities are uncommon. The majority represent atypical lipomatous tumors or well-differentiated liposarcomas. On rare occasions benign adipocytic tumors, such as hibernoma may present as huge, deep-lying subfascial masses. As a consequence of the deep location and usually heterogeneous signal intensities in imaging, they are particularly at risk to be misinterpreted as liposarcomas on clinical grounds. Furthermore, the rarity and thus limited familiarity with the morphological appearance and spectrum still represent a pitfall for the histopathological assessment.
Asunto(s)
Liposarcoma/patología , Neoplasias de los Músculos/patología , Femenino , Humanos , Liposarcoma/cirugía , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neoplasias de los Músculos/cirugía , Músculo Esquelético/patología , MusloRESUMEN
BACKGROUND: Adaptive desensitization still remains the only causative therapy for acetylsalicylic acid (ASA) hypersensitivity and is carried out nearly worldwide. To date there are hardly any data available on disease development under current desensitization therapy and longitudinal data in particular are missing. STUDY DESIGN: Out of a large collective of patients with proven hypersensitivity to ASA, 194 patients with initiated desensitization treatment were observed for periods up to 5 years (average 32 months). RESULTS: Patients with immediate reactions to systemic challenge tests revealed a response rate of 77% after 12 months of therapy. In this period 12% reached complete remission, 38% showed a clear reduction in symptoms, 32% reached partial remission, 13% remained unchanged and 5% suffered from disease progression. CONCLUSION: Adaptive desensitization therapy for hypersensitivity to ASA has been shown to be an effective causative therapy and chronic hyperplastic sinusitis as well as bronchial asthma could be improved. For the determination of maintenance dosages and required time periods more data are needed.
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Aspirina/efectos adversos , Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/inmunología , Hipersensibilidad a las Drogas/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: Balloon dilation of the Eustachian tube has recently been introduced as a novel and minimally invasive method for treating chronic obstructive Eustachian tube dysfunction. For the first time worldwide, we assessed the role of this technique in a large cohort of children with Eustachian tube dysfunction that did not respond to other treatments and in whom a tumor could be ruled out as the cause. STUDY DESIGN: This study is a retrospective analysis. METHODS: We retrospectively analyzed the medical records of 66 children (mean age 8.12 years, range 4-14 years) who underwent balloon dilation of the Eustachian tube using the Bielefeld balloon catheter. RESULTS: There were no complications during surgery. Clinical symptoms improved in more than 80% of the patients. No patient reported a deterioration of symptoms. Of the participating parents, over 80% were very satisfied or satisfied with the treatment outcome. CONCLUSION: Balloon dilation is a rapid, simple, and safe method for treatment of both adults and children with Eustachian tube dysfunction that does not respond to other treatments. Further studies, ideally multicenter studies, are required in order to optimize the definition of existing and potential new indications for this treatment approach, as well as to establish this treatment in the management of children with refractory chronic Eustachian tube dysfunction.
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Cateterismo/métodos , Dilatación/métodos , Enfermedades del Oído/cirugía , Trompa Auditiva/cirugía , Procedimientos Quirúrgicos Otológicos/métodos , Adolescente , Niño , Preescolar , Enfermedad Crónica , Enfermedades del Oído/diagnóstico por imagen , Femenino , Humanos , Masculino , Radiografía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: High-dose corticosteroids are currently recommended for idiopathic sudden sensorineural hearing loss (ISSNHL) treatment. Intratympanic injections (ITI) are of growing importance, especially in cases of therapy resistance. The selection of patients for this procedure in SSNHL has not been adequately examined so far. STUDY DESIGN: A total of 77 patients with ISSNHL after ineffective systemic pretreatment underwent intratympanic administration of dexamethasone and hyaluronic acid. Improvement after treatment was determined by pure tone audiometry for both ears before and of the treated ear after ITI. RESULTS: In this study 34 female and 43 male patients with mean age of 57 years showed a pre-ITI hearing loss of 35 dB in the lower frequencies and 69 dB in the higher frequencies. The mean hearing gain was 10 dB and the response rate was 62%. Absolute hearing gain revealed significant improvements at 500 Hz, 1 kHz and 2 kHz. Under inclusion of contralateral thresholds there were hardly any differences up to 4 kHz. In a detailed analysis of responders moderate improvements could be observed even in higher frequencies. Overall, no relevant adverse events occurred. CONCLUSION: Treatment of ISSNHL resistant to systemic regimens by ITI of steroids provides an option that offers additional prospects of auditory improvement for affected patients. The presented results indicate that these modalities are also valid for patients with pancochlear ISSNHL.
Asunto(s)
Corticoesteroides/administración & dosificación , Dexametasona/administración & dosificación , Pérdida Auditiva Súbita/diagnóstico , Pérdida Auditiva Súbita/tratamiento farmacológico , Inyección Intratimpánica/métodos , Atención Secundaria de Salud/métodos , Enfermedad Aguda , Adyuvantes Inmunológicos/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios/administración & dosificación , Femenino , Humanos , Ácido Hialurónico/administración & dosificación , Masculino , Persona de Mediana Edad , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: Diverse forms of bone conduction devices (BCD; percutaneous or transcutaneous) provide successful and well-established therapies for conductional hearing loss (CHL). For patients in whom a surgical procedure is to be avoided for medical or personal reasons, instruments with head straps or bands, and bone conduction glasses are available. The current article presents and examines the audiological results of a newly developed, nonsurgical bone conducting device (C.A.I. BC811, bruckhoff hannover; C.A.I: Concha Anchored Instrument) that is fixed in the concha and transfers the sound to the cheekbone. METHODS: In this cross-over study, 4 CHL patients with minimal sensorineural components and existing treatment with a BCD were supplied with a BC811. Audiological outcomes with the optimized existing device and the BC811 were evaluated and compared at 2-weekly intervals. In addition to the aided versus unaided sound field thresholds, the monosyllabic Freiburg intelligibility test, hearing in noise (OlSa) and the subjective benefit of the treatment (APHAB questionnaire) were investigated. RESULTS: No significant differences between BC811 and the optimized existing devices were found in terms of aided thresholds in sound field, functional gain or monosyllabic intelligibility tests. The average aided improvement of the threshold was PTA4 = 29.4 ± 11.1 dB (mean ± standard deviation) with the BC811. The improvements in the monosyllabic intelligibility and hearing in noise tests were significant for both types of device and comparison between the device types revealed no significant differences. The subjective ratings of the perceived improvement reflected by the global APHAB score were positive and similar: 36.4 (control) and 33.4 (BC811). CONCLUSION: The comparison with BCDs demonstrated that the BC811 is a realistic and audiologically sufficient alternative to surgical solutions using percutaneous devices for patients with CHL.
Asunto(s)
Conducción Ósea , Corrección de Deficiencia Auditiva/instrumentación , Audífonos , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/rehabilitación , Adulto , Corrección de Deficiencia Auditiva/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Pruebas Auditivas , Humanos , Masculino , Persona de Mediana EdadRESUMEN
This article presents the case of a patient with a submandibular cervical tumor initially suspected to be a large lymph node or glomus tumor. However, the diagnostic workup prior to taking a biopsy sample revealed an extracranial aneurysm of the internal carotid artery. In order to prevent a permanent neurologic deficit arising from thromboembolism, the aneurysm was excluded by resection and arterial continuity was restored. Extracranial aneurysms of the internal carotid artery are rare, but serious differential diagnoses of cervical nodes. It is of paramount importance that this differential diagnosis be considered before initiating invasive diagnostics of these tumors.
Asunto(s)
Aneurisma/diagnóstico , Aneurisma/cirugía , Angiografía/métodos , Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/cirugía , Neoplasias de Cabeza y Cuello/diagnóstico , Adulto , Diagnóstico Diferencial , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Masculino , Resultado del Tratamiento , Ultrasonografía/métodosRESUMEN
BACKGROUND: In order to improve therapy for HNSCC patients, novel methods to predict and combat local and/or distant tumour relapses are urgently needed. This study has been dedicated to the hypothesis that Rac1, a Rho GTPase, is implicated in HNSCC insensitivity to chemo-radiotherapy resulting in tumour recurrence development. METHODS: Parental and radiation-resistant (IRR) HNSCC cells were used to support this hypothesis. All cells were investigated for their sensitivity to ionising radiation and cisplatin, Rac1 activity, its intracellular expression and subcellular localisation. Additionally, tumour tissues obtained from 60 HNSCC patients showing different therapy response were evaluated for intratumoral Rac1 expression. RESULTS: Radiation-resistant IRR cells also revealed resistance to cisplatin accompanied by increased expression, activity and trend towards nuclear translocation of Rac1 protein. Chemical inhibition of Rac1 expression and activity resulted in significant improvement of HNSCC sensitivity to ionising radiation and cisplatin. Preclinical results were confirmed in clinical samples. Although Rac1 was poorly presented in normal mucosa, tumour tissues revealed increased Rac1 expression. The most pronounced Rac1 presence was observed in HNSCC patients with poor early or late responses to chemo-radiotherapy. Tissues taken at recurrence were characterised not only by enhanced Rac1 expression but also increased nuclear Rac1 content. CONCLUSIONS: Increased expression, activity and subcellular localisation of Rac1 could be associated with lower early response rate and higher risk of tumour recurrences in HNSCC patients and warrants further validation in larger independent studies. Inhibition of Rac1 activity can be useful in overcoming treatment resistance and could be proposed for HNSCC patients with primary or secondary chemo-radioresistance.
Asunto(s)
Carcinoma de Células Escamosas/enzimología , Resistencia a Antineoplásicos , Neoplasias de Cabeza y Cuello/enzimología , Proteína de Unión al GTP rac1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Cisplatino/farmacología , Inhibidores Enzimáticos/farmacología , Femenino , Técnicas de Silenciamiento del Gen , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Concentración 50 Inhibidora , Masculino , Persona de Mediana Edad , ARN Interferente Pequeño/genética , Proteína de Unión al GTP rac1/antagonistas & inhibidores , Proteína de Unión al GTP rac1/genéticaRESUMEN
BACKGROUND: Unlike malignant primary central nervous system (CNS) tumours outcome data on non-malignant CNS tumours are scarce. For patients diagnosed from 1996 to 2002 5-year relative survival of only 85.0% has been reported. We investigated this rate in a contemporary patient cohort to update information on survival. METHODS: We followed a cohort of 3983 cases within the Austrian Brain Tumour Registry. All patients were newly diagnosed from 2005 to 2010 with a histologically confirmed non-malignant CNS tumour. Vital status, cause of death, and population life tables were obtained by 31 December 2011 to calculate relative survival. RESULTS: Overall 5-year relative survival was 96.1% (95% CI 95.1-97.1%), being significantly lower in tumours of borderline (90.2%, 87.2-92.7%) than benign behaviour (97.4%, 96.3-98.3%). Benign tumour survival ranged from 86.8 for neurofibroma to 99.7% for Schwannoma; for borderline tumours survival rates varied from 83.2 for haemangiopericytoma to 98.4% for myxopapillary ependymoma. Cause of death was directly attributed to the CNS tumour in 39.6%, followed by other cancer (20.4%) and cardiovascular disease (15.8%). CONCLUSION: The overall excess mortality in patients with non-malignant CNS tumours is 5.5%, indicating a significant improvement in survival over the last decade. Still, the remaining adverse impact on survival underpins the importance of systematic registration of these tumours.
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Enfermedades del Sistema Nervioso Central/mortalidad , Adolescente , Adulto , Austria/epidemiología , Enfermedades del Sistema Nervioso Central/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Tasa de Supervivencia , Adulto JovenRESUMEN
Allergen-specific immunotherapy for grass pollen allergy has been reported to be effective in up to 85% of patients. Sensitisation to profilin and calcium-binding protein (CBP) can possibly influence treatment results and may thus be a reason for treatment failures. During a study period of 3 years, the distribution patterns of antibodies to marker allergens were continuously investigated in all blood serum samples with a level of immunoglobulin E antibodies to timothy and birch pollen higher than 0.7 kUA/l (n = 556). Sensitisation to timothy grass pollen alone was found in 33% of the cases, to birch pollen alone in 19%, and to both in 48%. The group of polysensitised patients showed an inhomogenous distribution of antibodies to marker allergens. IgE against minor allergens was detected in 40%. Sensitisation to major allergens, especially to the major birch allergen, was not present in 13% of the polysensitised patients. Of the patients who were sensitised to minor allergens, 82% were sensitised to profilin, 11% to CBP, and 8% to both profilin and CBP. Profilin and CBP frequently cause polysensitisations to pollen. The data obtained justify the measurement of serum levels of antibodies to marker allergens in patients who are sensitised to more than one group of allergens.
Asunto(s)
Anticuerpos/inmunología , Betula/inmunología , Proteínas de Unión al Calcio/inmunología , Inmunoglobulina E/inmunología , Phleum/inmunología , Polen/inmunología , Profilinas/inmunología , Rinitis Alérgica Perenne/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Reacciones Cruzadas/inmunología , Desensibilización Inmunológica , Femenino , Humanos , Inmunización , Masculino , Persona de Mediana Edad , Rinitis Alérgica , Rinitis Alérgica Perenne/terapia , Adulto JovenRESUMEN
Syndromic hearing loss is responsible for approximately 30% of cases of inherited hearing loss. The syndromic form can be differentiated from nonsyndromic hearing loss by the presence of associated symptoms in other organ systems. While for many forms of syndromic hearing loss the individual genes responsible have been identified, the etiology of other associated symptoms remains unclear. The role of the ENT physician is to select appropriate clinical and genetic diagnostic tools based on the presentation of the patient and to subsequently initiate and perform the required hearing loss therapy.