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PURPOSE: To investigate if infertility patients and physicians apply a traditional biomedical model of disease in their conceptualisation of infertility, examine any contradictions and conflicts in conceptualisations, and examine areas of concordance and discordance between physicians and patients. METHODS: Semi-structured interviews were conducted with 20 infertility patients and 18 infertility physicians between September 2010 and April 2012. Interviews were analysed qualitatively to determine physician and patient conceptualisations of infertility, reactions to the definition of infertility as a disease, and potential benefits and concerns related to application of a disease label to the condition. RESULTS: Most physicians (n = 14/18) and a minority of patients (n = 6/20) were supportive of defining infertility as a disease. Many of the patients who agreed with classifying infertility as a disease expressed that they had not personally defined it as such previously. Physicians (n = 14) and patients (n = 13) described potential benefits of a disease label, including increases in research funding, insurance coverage, and social acceptability. Some patients (n = 10) described potential stigma as a negative consequence. When describing appraisals of infertility, both physicians (n = 7) and patients (n = 8) invoked religious/spiritual concepts. The potential for religious/spiritual appraisal to contribute to stigmatising or de-stigmatising infertility was discussed. CONCLUSION: Our findings contradict the assumption that infertility physicians and patients are fully supportive of defining infertility as a disease. While potential benefits of the disease label were recognised by both groups, caution against potential for stigmatisation and unsolicited invocation of religion/spirituality suggest a more holistic model may be appropriate.
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Copper bactericides are routinely used to control Xanthomonas perforans (XP), causal agent of bacterial spot of tomato. Given the widespread tolerance to copper in XP strains in FL, USA, nanotechnology-based elemental composites have gained interest for their potential applications in agriculture in part due to their enhanced antimicrobial properties and toxicity to copper-tolerant strains. However, little is known about the potential impact of conventional copper bactericides as well as nano-based elemental composites on soil microbial communities, as determined by high-throughput sequencing of the 16S rDNA. We compared the effects of 2 and 200 µg/mL of core-shell (CS), a metallic copper composite, and a conventional copper bactericide + mancozeb (Cu+Man) on the soil microbiome. These treatments were compared to three controls, the microbial profile of the soil prior to application of copper products, a water application, and spiking the soil with a soilborne phytobacterium, Ralstonia solanacearum (RS). The RS treatment was included to determine if downstream analysis could detect the artificial inoculation. Utilizing multiple ß diversity measurements, each emphasizing various tenets of ecology, provided a greater perspective of the effects the treatments had on the microbiome. Analysis of HTS data revealed that the two treatments containing field applied rates of metallic copper, CS 200 and Cu+Man, had the largest impact on the soil microbiome at seven-days posttreatment compared to water. However, we simulated field applied rates of CS 200 entering the soil by treating soil with CS 2 and determined this concentration had a negligible effect on the soil microbiome. IMPORTANCE Nanotechnology-based elemental composites have gained popularity for their potential applications in plant disease management due to their enhanced antimicrobial properties. However, little is known about their potential impact on the environment. Foliar applications of nano metallic composites upon leaching into the soil have the potential to impact soil microbial populations that in turn influence soil health. Utilizing multiple ß diversity measurements, high-throughput sequencing analysis revealed that field applied rates of metallic copper (200 µg/mL) from an advanced copper composite (core-shell [CS]) and a conventional copper bactericide in combination with mancozeb had the largest impact on the soil microbiome compared to water and nontreated control. To simulate leaching from the leaf surface, a lower concentration (2 µg/mL) of CS was also applied to the soil and had a negligible effect on the soil microbiome. Thus, field applied rates of CS may have a minimal effect on soil microbial communities.
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Cobre , Microbiota , Antibacterianos/farmacología , Cobre/farmacología , Humanos , Suelo , Microbiología del Suelo , Agua , XanthomonasRESUMEN
BACKGROUND: Multiple biologic and targeted synthetic disease-modifying rheumatic drugs (b/tsDMARDs) are approved for the management of rheumatoid arthritis (RA), including TNF inhibitors (TNFi), bDMARDs with other modes of action (bDMARD-OMA) and Janus kinase inhibitors (JAKi). Combination of b/tsDMARDs with conventional synthetic DMARDs (csDMARDs) is recommended, yet monotherapy is common in practice. OBJECTIVE: To compare drug maintenance and clinical effectiveness of three alternative treatment options for RA management. METHODS: This observational cohort study was nested within the Swiss RA Registry. TNFi, bDMARD-OMA (abatacept or anti-IL6 agents) or the JAKi tofacitinib (Tofa) initiated in adult RA patients were included. The primary outcome was overall drug retention. We further analysed secondary effectiveness outcomes and whether concomitant csDMARDs modified effectiveness, adjusting for potential confounding factors. RESULTS: 4023 treatment courses of 2600 patients were included, 1862 on TNFi, 1355 on bDMARD-OMA and 806 on Tofa. TNFi was more frequently used as a first b/tsDMARDs, at a younger age and with shorter disease duration. Overall drug maintenance was significantly lower with TNFi compared with Tofa [HR 1.29 (95% CI 1.14 to 1.47)], but similar between bDMARD-OMA and Tofa [HR 1.09 (95% CI 0.96 to 1.24)]. TNFi maintenance was decreased when prescribed without concomitant csDMARDs [HR: 1.27 (95% CI 1.08 to 1.49)], while no difference was observed for bDMARD-OMA or Tofa maintenance with respect to concomitant csDMARDs. CONCLUSION: Tofa drug maintenance was comparable with bDMARDs-OMA and somewhat higher than TNFi. Concomitant csDMARDs appear to be required for optimal effectiveness of TNFi, but not for bDMARD-OMA or Tofa.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Piperidinas/uso terapéutico , Pirimidinas/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Abatacept/uso terapéutico , Adulto , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , SuizaRESUMEN
Bacterial spot, caused by Xanthomonas spp., is a highly destructive disease of tomatoes worldwide. Copper (Cu) bactericides are often ineffective due to the presence of Cu-tolerant strains. Magnesium oxide (MgO) is an effective alternative to Cu bactericides against Xanthomonas spp. However, the effects of particle size on bactericidal activity and fruit elemental levels are unknown. In this study, nano (20 nm) and micron (0.3 and 0.6 µm) size MgO particles were compared for efficacy. Nano MgO had significantly greater in vitro bactericidal activity against Cu-tolerant X. perforans than micron MgO at 25-50 µg/ml. In field experiments nano and micron MgO applied at 200 and 1,000 µg/ml were evaluated for disease control. Nano MgO at 200 µg/ml was the only treatment that consistently reduced disease severity compared to the untreated control. Inductively Coupled Plasma Optical Emission Spectroscopy revealed that nano MgO applications did not significantly alter Mg, Cu, Ca, K, Mn, P and S accumulation compared to fruits from the untreated plots. We demonstrated that although both nano MgO and micron MgO had bactericidal activity against Cu-tolerant strains in vitro, only nano MgO was effective in bacterial spot disease management under field conditions.
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Antibacterianos/farmacología , Óxido de Magnesio/farmacología , Enfermedades de las Plantas/terapia , Solanum lycopersicum/microbiología , Xanthomonas/efectos de los fármacos , Antibacterianos/química , Protección de Cultivos , Frutas/microbiología , Óxido de Magnesio/química , Nanopartículas/química , Tamaño de la Partícula , Enfermedades de las Plantas/microbiología , Xanthomonas/aislamiento & purificaciónRESUMEN
PURPOSE: The purpose of this study was to review a case comprised of a cervical spinal epidural abscess, cervical and thoracic paraspinous edema, and widening of the right thoracic neural foramen secondary to a phlegmon. METHODS: We reviewed the case of a spinal epidural abscess managed medically in a 4-year-old male and performed a review of the literature with 15 other cases that have previously been reported. RESULTS: The current mainstay of treatment is largely variant but generally falls into a laminectomy-based surgical approach or longstanding antibiotics. Our review of the literature concluded that there are currently no clear guidelines established to recommend treatment, and current practice is largely based on the discretion of the pediatric neurosurgeon. CONCLUSIONS: Based on the literature review, and our personal case illustration, we conclude that an antibiotic-based treatment is a valid approach for therapy if initiated promptly in a pediatric patient with no neurological deficit.
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Celulitis (Flemón)/tratamiento farmacológico , Edema/tratamiento farmacológico , Absceso Epidural/tratamiento farmacológico , Enfermedades de la Columna Vertebral/tratamiento farmacológico , Antibacterianos/uso terapéutico , Ceftriaxona/uso terapéutico , Celulitis (Flemón)/complicaciones , Celulitis (Flemón)/diagnóstico por imagen , Preescolar , Daptomicina/uso terapéutico , Edema/complicaciones , Edema/diagnóstico por imagen , Absceso Epidural/complicaciones , Absceso Epidural/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Enfermedades de la Columna Vertebral/complicaciones , Enfermedades de la Columna Vertebral/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Bacterial spot of tomato is caused by Xanthomonas gardneri, X. euvesicatoria, X. perforans, and X. vesicatoria. Current diagnostic methods for the pathogens are not in-field assays. Recombinase polymerase amplification (RPA) is ideal for in-field detection assays, because it is an isothermal technique that is rapid and more tolerant to inhibitors compared with polymerase chain reaction. Hence, novel RPA probes and primers were designed to amplify regions of the hrcN gene of X. gardneri, X. euvesicatoria, and X. perforans. The X. gardneri RPA is specific to X. gardneri with a detection limit of 106 CFU/ml and detected X. gardneri in lesions from naturally (n = 6) or artificially (n = 18) infected plants. The X. euvesicatoria RPA detects both X. euvesicatoria and X. perforans with a detection limit of 106 CFU/ml and detected both pathogens in plants artificially infected (n = 36) or naturally infected (n = 85) with either X. euvesicatoria or X. perforans. The X. perforans RPA is specific to X. perforans with a detection limit of 107 CFU/ml. Although the X. perforans RPA assay was unable to detect X. perforans from lesions, the X. euvesicatoria RPA was successfully used in field to detect X. perforans from symptomatic field samples (n = 31). The X. perforans RPA was then used to confirm the pathogen in the laboratory. The X. euvesicatoria and X. gardneri RPA is promising for rapid, real-time in-field detection of bacterial spot and one of the first developed among plant pathogenic bacteria.
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Técnicas de Tipificación Bacteriana , Dermatoglifia del ADN , Recombinasas , Solanum lycopersicum , Xanthomonas , Cartilla de ADN , Solanum lycopersicum/microbiología , Técnicas de Amplificación de Ácido Nucleico , Enfermedades de las Plantas , Xanthomonas/genéticaRESUMEN
Bacterial spot caused by Xanthomonas perforans causes significant damage on tomato in Florida. Due to the presence of copper (Cu)-tolerant X. perforans strains, Cu bactericides are not effective in disease management. Hence, there is a critical need to find alternatives for Cu. Antibacterial activity of magnesium oxide (Nano-MgO), and other metal oxide nanoparticles, were evaluated against a Cu-tolerant and -sensitive X. perforans strain. In vitro experiments demonstrated high antibacterial activity of Nano-MgO against both strains compared with the commercial Cu. The minimum inhibitory concentration of Nano-MgO is 25 µg/ml and the minimum bactericidal concentration is 100 µg/ml against a Cu-tolerant X. perforans strain after 4 h of exposure. Structural changes in the bacterial membrane following exposure to Nano-MgO treatments compared with the controls were observed using transmission electron microscopy. In two greenhouse experiments with a Cu-tolerant strain, bacterial spot severity was significantly reduced by Nano-MgO at 200 µg/ml compared with Cu-ethylene bis-dithiocarbamate (grower standard), and the untreated control (P = 0.05). In three field experiments, Nano-MgO at 200 µg/ml significantly reduced disease severity with no negative impact on yield compared with the untreated control. Inductively coupled plasma mass spectrometric analysis of the fruit confirmed that Nano-MgO application did not lead to the accumulation of Mg, Cu, Ca, K, Mn, P, and S. This study is the first to demonstrate the potential of Nano-MgO against bacterial spot of tomato.
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Antibacterianos/farmacología , Óxido de Magnesio/farmacología , Enfermedades de las Plantas/terapia , Solanum lycopersicum/microbiología , Xanthomonas/efectos de los fármacos , Cobre , Enfermedades de las Plantas/microbiología , Xanthomonas/patogenicidadRESUMEN
Chronic wound healing disorders that occur as a result of a sulfur mustard (SM) exposure present a particular challenge. These chronic wounds are similar to other chronic wounds. In the past, it has been shown that mesenchymal stem cells (MSC) play an important role in the healing of chronic wounds. An important property to support wound healing is their ability to migrate. However, we were able to show that SM leads to a reduction in MSC migration even at low concentrations. Currently, exposed MSCs are still able to differentiate. Further alterations are not known. The current investigation therefore focused onto the question how SM affects MSC. MATERIAL & METHODS: The effect of SM on MSC was investigated. Here, the alkylation of DNA was considered, and DNA adducts were quantified over a period of 48h. The modification of the nuclei under the influence of SM was analyzed as well as proliferation of the cells by immunohistochemical staining with Ki-67 and quantification. For the quantification of the apoptosis rate, antibodies against cleaved Caspase-3, 8, and apoptosis inducing factor (AIF) were used. The senescence analysis was performed after histological staining against ß-galactosidase. Quantifications were carried out by using the TissueQuest System and the software TissueFAX. RESULTS: SM exposure of MSC results in a dose dependent formation of nuclear DNA adducts. 4h after exposure the cells display a decreasing concentration of DNA adducts. This process is accompanied by a change of nuclei shape but without an increase of apoptosis induction. In parallel the number of cells undergoing senescence increases as a function of the SM concentration. DISCUSSION: SM exposure of MSC leads to adduct formation on chromosomal DNA. These DNA adducts can be reduced without MSC are undergoing apoptosis. This indicates an active DNA damage response (DDR) pathway in combination with the formation of persistent nuclear DNA damage foci. This process is accompanied by a reduced capability of proliferation and a transition into the senescent state.
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Sustancias para la Guerra Química/toxicidad , Células Madre Mesenquimatosas/efectos de los fármacos , Gas Mostaza/toxicidad , Anciano , Anciano de 80 o más Años , Alquilación , Apoptosis/efectos de los fármacos , Factor Inductor de la Apoptosis/farmacología , Caspasas/metabolismo , Núcleo Celular/efectos de los fármacos , Núcleo Celular/ultraestructura , Proliferación Celular/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , ADN/efectos de los fármacos , Aductos de ADN , Femenino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , beta-Galactosidasa/metabolismoRESUMEN
Bacterial spot, caused by Xanthomonas spp., is a widespread and damaging bacterial disease of tomato (Solanum lycopersicum). For disease management, growers rely on copper bactericides, which are often ineffective due to the presence of copper-tolerant Xanthomonas strains. This study evaluated the antibacterial activity of the new copper composites core-shell copper (CS-Cu), multivalent copper (MV-Cu), and fixed quaternary ammonium copper (FQ-Cu) as potential alternatives to commercially available micron-sized copper bactericides for controlling copper-tolerant Xanthomonas perforans. In vitro, metallic copper from CS-Cu and FQ-Cu at 100 µg/ml killed the copper-tolerant X. perforans strain within 1 h of exposure. In contrast, none of the micron-sized copper rates (100 to 1,000 µg/ml) from Kocide 3000 significantly reduced copper-tolerant X. perforans populations after 48 h of exposure compared with the water control (P < 0.05). All copper-based treatments killed the copper-sensitive X. perforans strain within 1 h. Greenhouse studies demonstrated that all copper composites significantly reduced bacterial spot disease severity when compared with copper-mancozeb and water controls (P < 0.05). Although there was no significant impact on yield, copper composites significantly reduced disease severity when compared with water controls, using 80% less metallic copper in comparison with copper-mancozeb in field studies (P < 0.05). This study highlights the discovery that copper composites have the potential to manage copper-tolerant X. perforans and tomato bacterial spot.
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Antibacterianos/farmacología , Cobre/farmacología , Enfermedades de las Plantas/prevención & control , Solanum lycopersicum/microbiología , Xanthomonas/efectos de los fármacos , Enfermedades de las Plantas/microbiología , Xanthomonas/fisiologíaRESUMEN
Cadmium, cobalt, chromium, copper, manganese, nickel, zinc and lead concentrations were detected in feathers of Buff-breasted Sandpipers (Calidris subruficollis) captured during the non-breeding season and analyzed with relationship to body mass. Of these metals tested for, only copper levels (2.28 µg/g) were positively correlated with bird body mass. Zinc levels showed higher concentration (67.97 µg/g) than the other metals, and cadmium levels showed the lowest concentration (0.14 µg/g). Trace element concentrations were below toxicity levels for all tested chemicals and we suggest that this probably reflects that essential elements are maintained there by normal homeostatic mechanism and that no excessive environmental exposure to these elements during migration or on the wintering area is suggested by these results.
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Charadriiformes/metabolismo , Exposición a Riesgos Ambientales , Contaminantes Ambientales/metabolismo , Plumas/química , Metales Pesados/metabolismo , Animales , Monitoreo del Ambiente , Femenino , MasculinoRESUMEN
Abstract Cadmium, cobalt, chromium, copper, manganese, nickel, zinc and lead concentrations were detected in feathers of Buff-breasted Sandpipers (Calidris subruficollis) captured during the non-breeding season and analyzed with relationship to body mass. Of these metals tested for, only copper levels (2.28 µg/g) were positively correlated with bird body mass. Zinc levels showed higher concentration (67.97 µg/g) than the other metals, and cadmium levels showed the lowest concentration (0.14 µg/g). Trace element concentrations were below toxicity levels for all tested chemicals and we suggest that this probably reflects that essential elements are maintained there by normal homeostatic mechanism and that no excessive environmental exposure to these elements during migration or on the wintering area is suggested by these results.
Resumo As concentrações de cádmio, cobalto, cromo, cobre, manganês, níquel, zinco e chumbo foram detectadas em penas de Maçarico-acanelado (Calidris subruficollis) capturados durante o período de invernada e analisados em relação a massa corporal. Destes metais analisados, somente os níveis de cobre (2,28 µg/g) foram correlacionados positivamente com a massa corporal dos indivíduos. Níveis de zinco apresentaram-se mais altos (67,97 µg/g) que outros metais e os níveis de cádmio apresentaram as menores concentrações (0,14 µg/g). As concentrações dos elementos-traços estão abaixo dos níveis de toxicidade em todos os testes químicos e sugerimos que isto provavelmente ocorre pela manutenção dos elementos essenciais através do mecanismo normal de homeostase e não reflete a exposição destes elementos durante a migração ou nas áreas de invernada.
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Animales , Femenino , Masculino , Charadriiformes/metabolismo , Exposición a Riesgos Ambientales , Contaminantes Ambientales/metabolismo , Plumas/química , Metales Pesados/metabolismo , Monitoreo del AmbienteRESUMEN
The Human Proteome Project (HPP) is designed to generate a comprehensive map of the protein-based molecular architecture of the human body, to provide a resource to help elucidate biological and molecular function, and to advance diagnosis and treatment of diseases. Within this framework, the chromosome-based HPP (C-HPP) has allocated responsibility for mapping individual chromosomes by country or region, while the biology/disease HPP (B/D-HPP) coordinates these teams in cross-functional disease-based groups. Chromosome 6 (Ch6) provides an excellent model for integration of these two tasks. This metacentric chromosome has a complement of 1002-1034 genes that code for known, novel or putative proteins. Ch6 is functionally associated with more than 120 major human diseases, many with high population prevalence, devastating clinical impact and profound societal consequences. The unique combination of genomic, proteomic, metabolomic, phenomic and health services data being drawn together within the Ch6 program has enormous potential to advance personalized medicine by promoting robust biomarkers, subunit vaccines and new drug targets. The strong liaison between the clinical and laboratory teams, and the structured framework for technology transfer and health policy decisions within Canada will increase the speed and efficacy of this transition, and the value of this translational research. BIOLOGICAL SIGNIFICANCE: Canada has been selected to play a leading role in the international Human Proteome Project, the global counterpart of the Human Genome Project designed to understand the structure and function of the human proteome in health and disease. Canada will lead an international team focusing on chromosome 6, which is functionally associated with more than 120 major human diseases, including immune and inflammatory disorders affecting the brain, skeletal system, heart and blood vessels, lungs, kidney, liver, gastrointestinal tract and endocrine system. Many of these chronic and persistent diseases have a high population prevalence, devastating clinical impact and profound societal consequences. As a result, they impose a multi-billion dollar economic burden on Canada and on all advanced societies through direct costs of patient care, the loss of health and productivity, and extensive caregiver burden. There is no definitive treatment at the present time for any of these disorders. The manuscript outlines the research which will involve a systematic assessment of all chromosome 6 genes, development of a knowledge base, and development of assays and reagents for all chromosome 6 proteins. We feel that the informatic infrastructure and MRM assays developed will place the chromosome 6 consortium in an excellent position to be a leading player in this major international research initiative. This article is part of a Special Issue: Can Proteomics Fill the Gap Between Genomics and Phenotypes?
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Enfermedades Genéticas Congénitas/genética , Proyecto Genoma Humano/organización & administración , Canadá , Cromosomas Humanos Par 6 , Enfermedad Crónica , Enfermedades Genéticas Congénitas/diagnóstico , Genómica , Antígenos HLA/genética , Cadenas beta de HLA-DQ/genética , Cadenas beta de HLA-DQ/metabolismo , Humanos , Ligandos , Complejo Mayor de Histocompatibilidad/genética , Proteínas de la Membrana/genética , Proteoma/metabolismo , Factores de Transcripción/genéticaRESUMEN
In radiology the use of internet resources is part of the daily routine. The critical selection of but not the access to radiologically relevant information is the key topic in internet use. We offer a selection of reviewed internet sources for radiologists. We present sources that offer guidance in decision-making in daily routine as well as internet sources on technical topics in radiology. Case selection and radiological search engines are helpful sites to begin an internet research. Online anatomy sites can be of assistance for interpretation of findings in radiology. Writing and publishing scientific works in radiology requires access to numerous internet services, a positive selection of which are reviewed in the present article. A variety of freeware is available on the internet, some of which may be a substantial benefit to projects in radiology.
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Minería de Datos/métodos , Conocimientos, Actitudes y Práctica en Salud , Difusión de la Información/métodos , Internet , RadiologíaRESUMEN
The potentials and pitfalls of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) in the diagnosis of large vessel vasculitis are summarized in this review article. With the ability to visualize the lumen and vessel walls of large and medium sized arteries, MRI and MRA have great potential to play a unique role in the diagnosis of large vessel vasculitis. This is underlined by the fact that mural inflammatory changes typically involve uptake of contrast agent that can be visualized with MRI. The cranial, intracranial and extracranial involvement pattern can be studied in a combined approach including an MRI examination of the superficial cranial arteries and an MRA examination of the thoracic aorta with its major supra-aortic branches. Typical MRI sequence parameters are given including monophasic MRA and time-resolved MRA protocols at 3 T. The MRI and MRA techniques have the potential to determine the most suitable (inflamed) segment for temporal artery biopsy and to monitor treatment. Initial results of multicenter studies for the diagnostic accuracy of these relatively new methods are expected soon. The MRA technique is recognized as an interesting alternative to invasive catheter angiography for the evaluation of central nervous system (CNS) vasculitis.
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Aumento de la Imagen/métodos , Angiografía por Resonancia Magnética/métodos , Vasculitis/patología , HumanosRESUMEN
BACKGROUND: Positron emission tomography-computed tomography (PET-CT) is a useful diagnostic tool to detect metastases in patients with malignancy. False positives have been reported in cases of inflammation and tissue regeneration. CASE REPORT: Over a period of 2 years, a 32-year-old woman with hepatocellular carcinoma and multiple bone metastases received three treatments of radiation therapy to a bone metastasis in the 5th left rib. Restaging with [18F]fluorodeoxyglucose (FDG) PET-CT showed increased uptake within the cardiac apex highly suspicious for a myocardial metastasis. Because the patient was asymptomatic, additional magnetic resonance imaging (MRI) of the heart was performed demonstrating radiation-associated changes but no evidence for metastases. CONCLUSION: PET-CT is a well-established diagnostic tool in metastatic diseases but its results should always be correlated with the clinical picture of the patient and previous treatments to rule out false positives.
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Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/radioterapia , Neoplasias Óseas/secundario , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/secundario , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/secundario , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Imagen Multimodal , Miocardio/patología , Cuidados Paliativos , Tomografía de Emisión de Positrones , Costillas/diagnóstico por imagen , Costillas/efectos de la radiación , Tomografía Computarizada por Rayos X , Neoplasias Óseas/patología , Carcinoma Hepatocelular/patología , Errores Diagnósticos , Fluorodesoxiglucosa F18 , Neoplasias Cardíacas/patología , Humanos , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética , Estadificación de Neoplasias , Traumatismos por Radiación/diagnóstico por imagen , Traumatismos por Radiación/patología , Planificación de la Radioterapia Asistida por Computador , Costillas/patologíaRESUMEN
BACKGROUND: Topical corticosteroids and calcineurin inhibitors are well-known treatments of atopic dermatitis (AD) but differ in their efficacy and side effects. We recently showed that betamethasone valerate (BM) although clinically more efficient impaired skin barrier repair in contrast to pimecrolimus in AD. OBJECTIVE: This study elucidates the mode of action of topical BM and pimecrolimus cream in AD. METHODS: Lesional AD skin samples after topical treatment with either BM or pimecrolimus were subjected to gene expression profile analysis. RESULTS: Betamethasone valerate resulted in a significant reduction in mRNA levels of genes encoding markers of immune cells and inflammation, dendritic cells, T cells, cytokines, chemokines, and serine proteases, whereas pimecrolimus exerted minor effects only. This corroborates the clinical finding that BM reduces inflammation more effectively than pimecrolimus. Genes encoding molecules important for skin barrier function were differently affected. Both BM and pimecrolimus normalized the expression of filaggrin and loricrin. BM, but not pimecrolimus, significantly reduced the expression of rate-limiting enzymes for lipid synthesis and the expression of involucrin and small proline-rich proteins, which covalently bind ceramides. This may explain the lack of restoration of functional stratum corneum layers observed after BM treatment. CONCLUSION: The gene expression profiles are consistent with our previous findings that corticosteroids may exert a more potent anti-inflammatory effect but may impair the restoration of the skin barrier. Corticosteroids are still the main treatment for severe and acutely exacerbated AD; pimecrolimus may be preferable for long-term treatment and stabilization.
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Betametasona/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Perfilación de la Expresión Génica , Piel/efectos de los fármacos , Tacrolimus/análogos & derivados , Adulto , Betametasona/farmacología , Calcineurina/farmacología , Calcineurina/uso terapéutico , Inhibidores de la Calcineurina , Permeabilidad de la Membrana Celular/efectos de los fármacos , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Método Doble Ciego , Femenino , Proteínas Filagrina , Glucocorticoides/farmacología , Glucocorticoides/uso terapéutico , Humanos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Proteínas/genética , Proteínas/metabolismo , Piel/metabolismo , Piel/patología , Tacrolimus/farmacología , Tacrolimus/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Medical curricula are currently being reformed in order to establish superordinated learning objectives, including, e.g., diagnostic, therapeutic and preventive competences. This requires a shifting from traditional teaching methods towards interactive and case-based teaching concepts. Conceptions, initial experiences and student evaluations of a novel radiological course Co-operative Learning In Clinical Radiology (CLICR) are presented in this article. MATERIALS AND METHODS: A novel radiological teaching course (CLICR course), which combines different innovative teaching elements, was established and integrated into the medical curriculum. Radiological case vignettes were created for three clinical teaching modules. By using a PC with PACS (Picture Archiving and Communication System) access, web-based databases and the CASUS platform, a problem-oriented, case-based and independent way of learning was supported as an adjunct to the well established radiological courses and lectures. Student evaluations of the novel CLICR course and the radiological block course were compared. RESULTS: Student evaluations of the novel CLICR course were significantly better compared to the conventional radiological block course. Of the participating students 52% gave the highest rating for the novel CLICR course concerning the endpoint overall satisfaction as compared to 3% of students for the conventional block course. The innovative interactive concept of the course and the opportunity to use a web-based database were favorably accepted by the students. Of the students 95% rated the novel course concept as a substantial gain for the medical curriculum and 95% also commented that interactive working with the PACS and a web-based database (82%) promoted learning and understanding. CONCLUSION: Interactive, case-based teaching concepts such as the presented CLICR course are considered by both students and teachers as useful extensions to the radiological course program. These concepts fit well into competence-oriented curricula.
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Instrucción por Computador/métodos , Curriculum , Evaluación Educacional , Internado y Residencia/estadística & datos numéricos , Sistemas de Información Radiológica/estadística & datos numéricos , Radiología/educación , Interfaz Usuario-Computador , Estudios de Casos y Controles , Alemania , EnseñanzaRESUMEN
Patients with ESCC (squamous cell carcinoma of the esophagus) are most commonly diagnosed with locally advanced tumor stages. Early metastatic disease and late diagnosis are common reasons responsible for this tumor's poor clinical outcome. The prognosis of esophageal cancer is very poor because patients usually do not have symptoms in early disease stages. Squamous cell carcinoma of the esophagus frequently complicates patients with multiple co-morbidities and these patients often require interdisciplinary diagnosis and treatment procedures. At present time, neoadjuvant radiation therapy and chemotherapy followed by surgery are regarded as the international standard of care. Meta-analyses have confirmed that this approach provides the patient with better local tumor control and an increased overall survival rate. It is recommended that patients with positive tumor response to neoadjuvant therapy and who are poor surgical candidates should consider definitive radiochemotherapy without surgery as a treatment option. In future, EGFR antibodies may also be administered to patients during therapy to improve the current treatment effectiveness. Positron-emission tomography proves to be an early response-imaging tool used to evaluate the effect of the neoadjuvant therapy and could be used as a predictive factor for the survival rate in ESCC. The percentage proportions of residual tumor cells in the histopathological analyses represent a gold standard for evaluating the response rate to radiochemotherapy. In the future, early response evaluation and molecular biological tests could be important diagnostic tools in influencing the treatment decisions of ESCC patients.
Asunto(s)
Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Esofagectomía , Terapia Neoadyuvante , Carcinoma de Células Escamosas/patología , Quimioterapia Adyuvante , Terapia Combinada , Neoplasias Esofágicas/patología , Humanos , Metaanálisis como Asunto , Estadificación de Neoplasias , Radioterapia Adyuvante , Nivel de Atención , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: Insulin-like growth factor (IGF)-1, -2 and Insulin like growth factor binding proteins (IGFBP) are involved in the proliferation and differentiation of cells. It has never been evaluated, if the IGF-system can serve as a tumor marker in neoplasms. METHODS: In our prospective study 163 patients with colorectal cancer (22), prostate cancer (21), head and neck tumors (17), lymphomas (20), lung cancer (34) and other entities (49) were analysed for their IGF and IGFBP serum levels at the beginning and the end of radiotherapy and compared to 13 healthy people. Subgroups of patients with local tumor disease versus metastatic disease, primary and recurrent therapy and curative versus palliative therapy were compared. RESULTS: The serum levels of IGF-2 were significantly elevated in patients with prostate and colorectal cancer. However, sensitivity and specificity were only 70%. IGFBP-2 serum levels were elevated in patients with head and neck tumors. Again sensitivity and specificity were only 73%. A difference between local disease and metastatic disease could not be found. A difference between IGF serum levels before and after radiotherapy could not be detected. CONCLUSION: The IGF-system cannot serve as a new tumor marker. The detected differences are very small, sensitivity and specificity are too low. IGF measurement is not useful for the evaluation of the success of radiotherapy in malignancies.
Asunto(s)
Biomarcadores de Tumor/sangre , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor II del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Neoplasias/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Locally advanced gastric cancers are characterized by poor prognosis. Clinical outcome can be improved if surgery becomes part of a multimodal treatment approach. The purpose of neoadjuvant treatment includes downsizing of the primary tumor, improvement of the T- and N- categories, and early therapy of micrometastasis. Several controlled clinical trials showed that neoadjuvant chemotherapy as well as neoadjuvant combined radio-chemotherapy, especially for tumors of the gastroesophageal junction, can improve the rate of primary R0 resections, relapse-free survival, and overall survival. While patients with locally advanced tumors clearly benefit from this strategy, the approach is still controversial in patients with early stage disease. Nonresponders do not benefit from neoadjuvant therapy. Therefore, response evaluation and response prediction are of great importance. After successful neoadjuvant chemotherapy, patients should undergo gastrectomy with D(2)-lymphadenectomy because of a high probability of lymph node metastasis. This article summarizes current developments in this field.