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1.
J Clin Neurosci ; 72: 438-446, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31911105

RESUMO

OBJECTIVE: The aim of the study is to develop a workflow to establish geometrical quality criteria for 3D printed anatomical models as a guidance for selecting the most suitable 3D printing technologies available in a clinical environment. METHODS: We defined the 3D geometry of a 25-year-old male patient's L4 vertebra and the geometry was then printed using two technologies, which differ in printing resolution and affordability: Fused Deposition Modelling (FDM) and Digital Light Processing (DLP). In order to measure geometrical accuracy, the 3D scans of two physical models were compared to the virtual input model. To compare surface qualities of these printing technologies we determined surface roughness for two regions of interest. Finally, we present our experience in the clinical application of a physical model in a congenital deformity case. RESULTS: The analysis of the distribution of the modified Hausdorff distance values along the vertebral surface meshes (99% of values <1 mm) of the 3D printed models provides evidence for high printing accuracy in both printing techniques. Our results demonstrate that the surface qualities, measured by roughness are adequate (~99% of values <0.1 mm) for both physical models. Finally, we implemented the FDM physical model for surgical planning. CONCLUSION: We present a workflow capable of determining the quality of 3D printed models and the application of a high quality and affordable 3D printed spine physical model in the pre operative planning. As a result of the visual guidance provided by the physical model, we were able to define the optimal trajectory of the screw insertion during surgery.

4.
Ideggyogy Sz ; 72(7-8): 227-235, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31517454

RESUMO

Background and purpose: 3D technologies (3D virtual and physical model, 3D printing, computer aided engineering, finite element analysis based simulations) play an important role in personalized spine surgery. Objective - In collaboration with AOSpine a global, online survey-based study was performed in order to determine the acceptance rate and the factors which stand against the wider spread of 3D technologies. Methods: A survey containing 21 questions was developed and divided into five pages, every page corresponding to one chapter. Our analysis is based on the responses of 282 spine surgeons from 57 countries. To interpret our results in a global context, we used the Human Development Index of the respondent's countries in comparisons. Results: Significant difference between the AOSpine regions (p ≤ 0.05) was found, with the highest acceptance in Asia-Pacific region. There was no significant difference in acceptance score according to the field of spine surgery, or the surgical experience in years (p=0.77, and p=0.19). In the case of public practice, we found significantly higher acceptance compared to private and mixed (public and private) surgical practice (p ≤ 0.05). The acceptance of the technology varied based on the respondent's resident country's Human Development Index and was significantly different between "Medium" vs "Very high" (p = 0.0005) and "High" vs "Very high" (p=0.019) category. Significant positive correlation was found between the acceptance score and the HDI score (Spearman test, ρ = 0.37, p = 0.007). The main limitation factor was identified as the lack of information. Conclusion: There is high interest among spine surgeons towards the incorporation of 3D technologies into the clinical practice. Education, the healthcare system, and the economic environment plays a major role in acceptance. Our results provide the basis of a strategy to promote the application of 3D technologies.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Impressão Tridimensional , Coluna Vertebral/cirurgia , Cirurgiões/psicologia , Humanos , Prática Profissional/estatística & dados numéricos , Fraturas da Coluna Vertebral/cirurgia , Traumatismos da Coluna Vertebral/cirurgia , Inquéritos e Questionários
7.
Eur Spine J ; 28(6): 1441-1447, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31006068

RESUMO

PURPOSE: Percutaneous cement discoplasty (PCD) is a minimally invasive surgical procedure, that can provide a segmental stabilizing and indirect decompression effect in case of severely degenerated discs characterized by vacuum phenomenon. The objective of this study was to evaluate the effects of PCD on spinopelvic radiological parameters and their associations with the clinical outcome. METHODS: Retrospective analysis of prospectively collected dataset of 28 patients (112 lumbar segments) who underwent single- or multilevel PCD was performed. Spinopelvic, intrasegmental and intersegmental parameters were measured on lumbar X-rays pre-, postoperatively and 6 months after the surgery. Correlations between radiological parameters and clinical outcome data were determined. RESULTS: Sacral slope significantly increased (p < .001), and pelvic tilt (p < .05) was decreased after the PCD procedure. Segmental and total lordosis (p < .05, p < .05) disc and foraminal height showed significantly increase (p < .001, p < .001) after procedure. Pain and disability (ODI) significantly decreased due to PCD. An association was found between postoperative increase in SS and improvement in ODI (r = 0.39, p < .05). The change in low back pain was correlated with segmental scoliosis correction (p < .001). Moderate correlation was detected between the increase in disc height and ODI (p < .05) as well as leg pain (p < .01). CONCLUSION: PCD is an effective minimally invasive technique to treat axial pain and disability related to severe lumbar disc degeneration. Our study shows that an improvement in lumbar alignment and a significant indirect foraminal decompression could be achieved with the procedure. These changes can significantly contribute to the pain relief and increase in the patients' functional capacity. These slides can be retrieved under Electronic Supplementary Material.

9.
Anal Biochem ; 566: 126-132, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30452893

RESUMO

Cell-based assays against cell surface receptor targets are essential in vitro models of target-based drug discovery. At the lead generation phase large-scale functional screening assays monitoring individual cellular readouts detect interactions between the compounds and the predefined pathways but might lack sufficient sensitivity owing to the complexity of downstream signaling pathways. Cellular label-free assays offer advantages over labeled detection approaches as they reflect whole-cell responses without the prerequisite of detecting only a single cellular analyte and introducing additional genetic manipulations in favor of the chosen detection method. The combination of a label-free assay and labeled assays might integrate the advantageous characteristics of both approaches with regards to added pharmacological information and a bigger pool of chemical starting material. Here we report multiplexing of dynamic mass redistribution label-free technology with HTRF-based cAMP detection on an alpha2c adrenergic receptor expressing cell line. Besides describing the challenging assay development work associated with the set goal, a pilot screening campaign on ca. 1600 compounds is also presented. The combined assay demonstrated the ability to detect relevant activities in both readouts. Interpretation of the results as well as an outlook for further possible opportunities and applications are also discussed.


Assuntos
AMP Cíclico/química , Descoberta de Drogas/métodos , Ensaios de Triagem em Larga Escala/métodos , Análise de Célula Única/métodos , Animais , Bioensaio/métodos , Técnicas Biossensoriais/métodos , Células CHO , Cricetulus , AMP Cíclico/metabolismo , Bases de Dados de Produtos Farmacêuticos , Fluorescência , Preparações Farmacêuticas/química , Receptores Adrenérgicos alfa 2/metabolismo
11.
ChemMedChem ; 13(20): 2177-2188, 2018 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-30113139

RESUMO

Fatty acid amide hydrolase (FAAH) can be targeted for the treatment of pain associated with various medical conditions. Herein we report the design and synthesis of a novel series of heterocyclic-N-carboxamide FAAH inhibitors that have a good alignment of potency, metabolic stability and selectivity for FAAH over monoacylglycerol lipase (MAGL) and carboxylesterases (CEs). Lead optimization efforts carried out with benzotriazolyl- and imidazolyl-N-carboxamide series led to the discovery of clinical candidate 8 l (3-(1-(cyclohexyl(methyl)carbamoyl)-1H-imidazol-4-yl)pyridine 1-oxide; BIA 10-2474) as a potent and long-acting inhibitor of FAAH. However, during a Phase I clinical trial with compound 8 l, unexpected and unpredictable serious neurological adverse events occurred, affecting five healthy volunteers, including the death of one subject.


Assuntos
Amidoidrolases/antagonistas & inibidores , Analgésicos/farmacologia , Óxidos N-Cíclicos/farmacologia , Inibidores Enzimáticos/farmacologia , Piridinas/farmacologia , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Analgésicos/química , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ensaios Clínicos Fase I como Assunto , Óxidos N-Cíclicos/administração & dosagem , Óxidos N-Cíclicos/efeitos adversos , Óxidos N-Cíclicos/química , Desenho de Drogas , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/química , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/química , Ratos , Relação Estrutura-Atividade
12.
Orv Hetil ; 159(26): 1065-1070, 2018 Jul.
Artigo em Húngaro | MEDLINE | ID: mdl-29936855

RESUMO

Ignác Semmelweis did not publish his discovery in Vienna - i.e., that the puerperal fever may be prevented by careful washing of the hand in chlorine solution (asepsis) - for ten years. The Medical Weekly started its publications edited by Lajos Markusovszky in Pest in 1857. Semmelweis as a professor of theoretical and practical obstetrics at the University of Pest published a study about puerperal fever in the first volume, and Hungarian physicians became familiar with Semmelweis' opinion from this medical journal. Semmelweis was not only an author of the Medical Weekly, but he also edited a supplement of the Medical Weekly entitled Gynaecology and Paediatry. The Medical Weekly published regular accounts of the work of the clinic written by lecturers of Semmelweis and articles describing the most interesting cases of the clinic. Orv Hetil. 2018; 159(26): 1065-1070.


Assuntos
Jornalismo Médico/história , Publicações Periódicas como Assunto/história , Docentes de Medicina/história , Feminino , História do Século XIX , Humanos , Hungria , Gravidez , Infecção Puerperal/história
18.
J Chem Phys ; 146(11): 114701, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28330352

RESUMO

During aluminium electrolysis, a ledge of frozen electrolytes is generally formed, attached to the sides of the cells. This ledge acts as a protective layer, preventing erosion and chemical attacks of both the electrolyte melt and the liquid aluminium on the side wall materials. The control of the sideledge thickness is thus essential in ensuring a reasonable lifetime for the cells. The key property for modelling and predicting the sideledge thickness as a function of temperature and electrolyte composition is the thermal conductivity. Unfortunately, almost no data is available on the thermal conductivity of the sideledge. The aim of this work is to alleviate this lack of data. For seven different samples of sideledge microstructures, recovered from post-mortem industrial electrolysis cells, the thermal diffusivity, the density, and the phase compositions were measured in the temperature range of 423 K to 873 K. The thermal diffusivity was measured with a laser flash technique and the average phase compositions by X-ray diffraction analysis. The thermal conductivity of the sideledge is deduced from the present experimental thermal diffusivity and density, and the thermodynamically assessed heat capacity. In addition to the present experimental work, a theoretical model for the prediction of the effective thermal transport properties of the sideledge microstructure is also proposed. The proposed model considers an equivalent microstructure and depends on phase fractions, porosity, and temperature. The strength of the model lies in the fact that only a few key physical properties are required for its parametrization and they can be predicted with a good accuracy via first principles calculations. It is shown that the theoretical predictions are in a good agreement with the present experimental measurements.

20.
Bioorg Med Chem Lett ; 27(4): 1062-1069, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28131713

RESUMO

Selective inhibition of Kv1.5, which underlies the ultra-rapid delayed rectifier current, IKur, has been pursued as a treatment for atrial fibrillation. Here we describe the discovery of MK-1832, a Kv1.5 inhibitor with improved selectivity versus the off-target current IKs, whose inhibition has been associated with ventricular proarrhythmia. MK-1832 exhibits improved selectivity for IKur over IKs (>3000-fold versus 70-fold for MK-0448), consistent with an observed larger window between atrial and ventricular effects in vivo (>1800-fold versus 210-fold for MK-0448). MK-1832 also exhibits an improved preclinical pharmacokinetic profile consistent with projected once daily dosing in humans.


Assuntos
Canal de Potássio Kv1.5/antagonistas & inibidores , Piridinas/farmacologia , Descoberta de Drogas , Humanos , Piridinas/farmacocinética , Relação Estrutura-Atividade
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