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BACKGROUND: A sufficient nitrogen supply is crucial for high-quality wheat yields. However, the use of nitrogen fertilization can also negatively influence ecosystems due to leaching or volatile atmospheric emissions. Drought events, increasingly prevalent in many crop production areas, significantly impact nitrogen uptake. Breeding more efficient wheat varieties is necessary to achieve acceptable yields with limited nitrogen and water. Crop root systems play a crucial role as the primary organ for absorbing water and nutrients. To investigate the impact of an enhanced root system on nitrogen and water use efficiency in wheat under various irrigation conditions, this study conducted two experiments using precision phenotyping platforms for controlled drought stress treatment. Experiment 1 involved four contrasting winter wheat genotypes. It included the Chinese variety Ning0604, carrying a quantitative trait locus (QTL) on chromosome 5B associated with a higher root dry biomass, and three elite German varieties, Elixer, Genius, and Leandrus. Experiment 2 compared near-isogenic lines (NIL) of the three elite varieties, each containing introgressions of the QTL on chromosome 5B linked to root dry mass. In both experiments, nitrogen partitioning was tracked via isotope discrimination after fertilization with 5 Atom % 15N-labeled KNO3-. RESULTS: In experiment 1 the quantification by 15N isotope discrimination revealed significantly (p < 0.05) higher nitrogen derived from fertilizer in the root organ for Ning0604 than those of the three German varieties. In experiment 2, two out of three NILs showed a significantly (p < 0.05) higher uptake of N derived from fertilizer than their respective recipient line under well-watered conditions. Furthermore, significantly lower transpiration rates (p < 0.1) were observed in one NIL compared to its respective recipient. CONCLUSIONS: The combination of the DroughtSpotter facility coupled with 15N tracer-based tracking of N uptake and remobilization extends the insight into the impact of genetically altered root biomass on wheat NUE and WUE under different water availability scenarios. The study shows the potential for how a modified genetic constitution of the locus on wheat chromosome 5B can reduce transpiration and enhance N uptake. The dependence of the observations on the recipient and water availability suggests a need for further research to investigate the interaction with genetic background traits.
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Nitrogênio , Locos de Características Quantitativas , Locos de Características Quantitativas/genética , Triticum/genética , Secas , Ecossistema , Fertilizantes , Melhoramento Vegetal , Água , Cromossomos , IsótoposRESUMO
INTRODUCTION: CYP2D6 and CYP2C19 functional status as defined by genotype is modulated by phenoconversion (PC) due to pharmacokinetic interactions. As of today, there is no data on the effect size of PC for CYP2C19 functional status. The primary aim of this study was to investigate the impact of PC on CYP2C19 functional status. METHODS: Two patient cohorts (total n=316; 44.2±15.4 years) were investigated for the functional enzyme status of CYP2C19 applying two different correction methods (PCBousman, PCHahn&Roll) as well as serum concentration and metabolite-to-parent ratio of venlafaxine, amitriptyline, mirtazapine, sertraline, escitalopram, risperidone, and quetiapine. RESULTS: There was a decrease in the number of normal metabolizers of CYP2C19 and an increase in the number of poor metabolizers. When controlled for age, sex, and, in the case of amitriptyline, venlafaxine, and risperidone, CYP2D6 functional enzyme status, an association was observed between the CYP2C19 phenotype/functional enzyme status and serum concentration of amitriptyline, sertraline, and escitalopram. DISCUSSION: PC of CYP2C19 changes phenotypes but does not improve correlations with serum concentrations. However, only a limited number of patients received perturbators of CYP2C19. Studies with large numbers of patients are still lacking, and thus, it cannot be decided if there are minor differences and which method of correction to use. For the time being, PC is relevant in individual patients treated with CYP2C19-affecting drugs, for example, esomeprazole. To ensure adequate serum concentrations in these patients, this study suggests the use of therapeutic drug monitoring.
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Amitriptilina , Citocromo P-450 CYP2D6 , Humanos , Citocromo P-450 CYP2D6/genética , Cloridrato de Venlafaxina , Farmacogenética , Sertralina , Risperidona , Escitalopram , Citocromo P-450 CYP2C19/genética , GenótipoRESUMO
BACKGROUND: Pharmacogenetics (PGx), especially in regard to CYP2D6, is gaining more importance in routine clinical settings. Including phenoconversion effects (PC) in result interpretation could maximize its potential benefits. However, studies on genetics of pharmacokinetic genes including the functional enzyme status are lacking. AIM: The retrospective analyses of clinical routine data aimed to investigating how the CYP2D6 functional enzyme status affects serum concentrations and metabolite-to-parent ratios of seven common psychotropic drugs and allows an evaluation of the relevance of this information for patient care. METHOD: Two patient cohorts (total n = 316; 44.2 ± 15.4 years) were investigated for the CYP2D6 functional enzyme status and its associations with drug exposure and metabolism of venlafaxine, amitriptyline, mirtazapine, sertraline, escitalopram, risperidone and quetiapine. RESULTS: We found an increase in intermediate and poor metabolizers, as well as a decrease in normal metabolizers of CYP2D6 when including PC. Moreover, we found associations between amitriptyline exposure with the phenoconversion-corrected activity score of CYP2D6 (Spearman correlation; p = 0.03), and risperidone exposure with CYP2D6 functional enzyme status (Kruskal-Wallis test; p = 0.01), as well as between metabolite-to-parent ratio of venlafaxine and risperidone with CYP2D6 functional enzyme status (Kruskal-Wallis test; p < 0.001; p = 0.05). CONCLUSION: The data stress the relevance of PC-informed PGx in psychopharmacological treatment and suggest that PC should be included in PGx result interpretation when PGx is implemented in routine clinical care, especially before initiating amitriptyline- or risperidone-treatment, to start with a dose adequate to the respective CYP2D6 functional enzyme status. Moreover, PGx and therapeutic drug monitoring should be used complementary but not alternatively.
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Antipsicóticos , Humanos , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Estudos Retrospectivos , Risperidona/farmacocinética , Farmacogenética , Cloridrato de Venlafaxina , Amitriptilina , Genótipo , Fenótipo , AntidepressivosRESUMO
OBJECTIVE: The FACT-PGx study was conducted to analyze barriers to implementation of pharmacogenetic testing in psychiatric hospitals in Germany and to propose solutions for its faster and easier implementation in all hospitals. METHODS: 104 patients (50% female) were genotyped and participated in the study. 67 completed a survey. To analyze the correlation between continuous data (age) of the survey, the wilcoxon rank test and for categorial data (education level, history of treatment and episodes), t-test was used. RESULTS: No patient declined to be genotyped. 99% believed that genotyping could help to shorten their hospital stay. Patients >40 years of age and with higher educational levels were willing to pay for the PGx (p=0.009). On average, patients were willing to pay 117.42 +/-140.49 and to wait 15.83+/- 8.92 days for the results. Processes differed significantly between routine laboratory screening and PGx testing which could be a barrier for implementation. CONCLUSION: Patients are not barriers to but enablers of an implementation of PGx. New process flows can be barriers, but can be overcome by optimization.
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Purpose: Pharmacogenetic counselling is a complex task and requires the efforts of an interdisciplinary team, which cannot be implemented in most cases. Therefore, simple rules could help to minimize the risk of medications incompatible with each other or with frequent genetic variants. Patients and Methods: One hundred and eighty-four multi-morbid Caucasian patients suffering from side effects or inefficient therapy were enrolled and genotyped. Their medication was analyzed by a team of specialists using Drug-PIN® (medication support system) and individual recommendations for 34 drug classes were generated. Results: In each of the critical drug classes, 50% of the drugs cannot be recommended to be prescribed in typical drug cocktails. PPIs and SSRI/SNRIs represent the most critical drug classes without showing a single favorable drug. Among the well-tolerated drugs (not recommended for less than 5% of the patients) are metamizole, celecoxib, olmesartan and famotidine. For each drug class, a ranking of active ingredients according to their suitability is presented. Conclusion: Genotyping and its profound analysis are not available in many settings today. The consideration of frequent alterations of metabolic elimination routes and drug-drug-gene interactions by using simple rankings can help to avoid many incompatibilities, side effects and inefficient therapies.
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BACKGROUND: Medication problems such as strong side effects or inefficacy occur frequently. At our university hospital, a consultation group of specialists takes care of patients suffering from medication problems. Nevertheless, the counselling of poly-treated patients is complex, as it requires the consideration of a large network of interactions between drugs and their targets, their metabolizing enzymes, and their transporters, etc. PURPOSE: This study aims to check whether a score-based decision-support system (1) reduces the time and effort and (2) suggests solutions at the same quality level. PATIENTS AND METHODS: A total of 200 multimorbid, poly-treated patients with medication problems were included. All patients were considered twice: manually, as clinically established, and using the Drug-PIN decision-support system. Besides diagnoses, lab data (kidney, liver), phenotype (age, gender, BMI, habits), and genotype (genetic variants with actionable clinical evidence I or IIa) were considered, to eliminate potentially inappropriate medications and to select individually favourable drugs from existing medication classes. The algorithm is connected to automatically updated knowledge resources to provide reproducible up-to-date decision support. RESULTS: The average turnaround time for manual poly-therapy counselling per patient ranges from 3 to 6 working hours, while it can be reduced to ten minutes using Drug-PIN. At the same time, the results of the novel computerized approach coincide with the manual approach at a level of > 90%. The holistic medication score can be used to find favourable drugs within a class of drugs and also to judge the severity of medication problems, to identify critical cases early and automatically. CONCLUSION: With the computerized version of this approach, it became possible to score all combinations of all alternative drugs from each class of drugs administered ("personalized medication landscape ") and to identify critical patients even before problems are reported ("medication alert"). Careful comparison of manual and score-based results shows that the incomplete manual consideration of genetic specialties and pharmacokinetic conflicts is responsible for most of the (minor) deviations between the two approaches. The meaning of the reduction of working time for experts by about 2 orders of magnitude should not be underestimated, as it enables practical application of personalized medicine in clinical routine.
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Farmacogenética , Polimedicação , Aconselhamento , Genótipo , Humanos , Lista de Medicamentos Potencialmente InapropriadosRESUMO
AIM OF THE STUDY: Botanicals used in Traditional Chinese Medicine (TCM) are a rich source for drug discovery and provide models for multi-component drug development. To facilitate the studies of the actions of TCM drugs and expand their applications, a comprehensive database is urgently required. METHODS: One online resource connects all the relevant data from multiple scientific sources and languages. Drug information from published TCM databases and the official Chinese Pharmacopoeia as well as specialized meta-websites such as Kew's Medicinal Plant Names Service was integrated on a higher level. RESULTS: Our database, SuperTCM, covers the aspects of TCM derived from medicinal plants, encompassing pharmacological recipes up to chemical compounds. It provides the information for 6516 TCM drugs (or "herbs") with 5372 botanical species, 55,772 active ingredients against 543 targets in 254 KEGG pathways associated with 8634 diseases. SuperTCM is freely available at http://tcm.charite.de/supertcm.
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Bases de Dados Factuais , Medicamentos de Ervas Chinesas/uso terapêutico , Linguística , Materia Medica/uso terapêutico , Medicina Tradicional Chinesa , Farmacologia em Rede , Integração de Sistemas , Animais , Bases de Dados de Compostos Químicos , Bases de Dados de Produtos Farmacêuticos , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Classificação Internacional de Doenças , Materia Medica/efeitos adversos , Farmacopeias como AssuntoRESUMO
The innovative strength of research performance is often measured in terms of inputs such as research funds or outputs such as patent applications. We present a novel indicator of pharmaceutical innovativeness that focuses on global medical breakthroughs and associated patents. According to this indicator, US companies account for 55 % of global medical breakthroughs from 2010 to 2019, and their German competitors account for about 9 %. In terms of underlying anchor patents, the dominance of the US is even larger, at 62 %, while only 7 % of anchor patents come from Germany. US universities hold 3.8 % of all anchor patents; German universities hold none. The weakness of German universities cannot be compensated by German non-university research institutes.
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PURPOSE: Inefficacy and safety concerns are main medications' problems, especially in the case of poly-therapies, when drug-drug interactions may alter the expected drug disposition. Ongoing efforts are aimed to establish drug selection processes aimed to preemptive evaluation of a plethora of factors affecting patient's specific drug response, including pharmacogenomic markers, in order to minimize prescription of improper medications. In previous years, we established at the University Hospital Sant'Andrea of Rome, Italy, a Precision Medicine Service based on a multi-disciplinary experts' team. The team is in charge to produce a drug therapy counselling report, including pharmacogenomic, pharmacokinetic and pharmacodynamic considerations. In this study, we aimed to evaluate the performance of this established "manual" process of therapy selection with a novel bioinformatic tool, the Drug-PIN system. PATIENTS AND METHODS: A total of 200 patients diagnosed with Major Depressive Disorders or a depressive episode in Bipolar Disorder, with at least three previous failed treatments, who underwent pharmacogenomic profiling and therapy counselling in the Sant'Andrea Hospital from 2017 to 2020. The baseline poly-therapy of these patients was re-evaluated and optimized by Drug-PIN. Results of the Drug-PIN poly-therapy evaluation/optimization were compared with the results of the original poly-therapy evaluation/optimization by therapy counselling. To compare the results between the two processes, the risk associated with each poly-therapy was classified as low, moderate, or high. RESULTS: The number of baseline poly-therapies classified in low-, moderate- or high-risk did not change significantly between manual system or Drug-PIN system. As the counselling process, also the Drug-PIN system produces a significant decrease in the predicted treatment-associated risk. CONCLUSION: Drug-PIN substantially replicates the output of the counselling process, allowing a substantial reduction in the time needed for therapy evaluation. Availability of an effective bioinformatic tool for proper drug selection is expected to exponentially increase the actuation of targeted therapy strategies.
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The development of new drugs for diseases is a time-consuming, costly and risky process. In recent years, many drugs could be approved for other indications. This repurposing process allows to effectively reduce development costs, time and, ultimately, save patients' lives. During the ongoing COVID-19 pandemic, drug repositioning has gained widespread attention as a fast opportunity to find potential treatments against the newly emerging disease. In order to expand this field to researchers with varying levels of experience, we made an effort to open it to all users (meaning novices as well as experts in cheminformatics) by significantly improving the entry-level user experience. The browsing functionality can be used as a global entry point to collect further information with regards to small molecules (â¼1 million), side-effects (â¼110 000) or drug-target interactions (â¼3 million). The drug-repositioning tab for small molecules will also suggest possible drug-repositioning opportunities to the user by using structural similarity measurements for small molecules using two different approaches. Additionally, using information from the Promiscuous 2.0 Database, lists of candidate drugs for given indications were precomputed, including a section dedicated to potential treatments for COVID-19. All the information is interconnected by a dynamic network-based visualization to identify new indications for available compounds. Promiscuous 2.0 is unique in its functionality and is publicly available at http://bioinformatics.charite.de/promiscuous2.
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Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Biologia Computacional/métodos , Bases de Dados de Produtos Farmacêuticos , Reposicionamento de Medicamentos/estatística & dados numéricos , SARS-CoV-2/efeitos dos fármacos , COVID-19/epidemiologia , COVID-19/virologia , Curadoria de Dados/métodos , Reposicionamento de Medicamentos/métodos , Humanos , Armazenamento e Recuperação da Informação/métodos , Internet , Pandemias , SARS-CoV-2/fisiologiaRESUMO
High-resolution visualization of surfaces of geologic interest, at a multitude of scales, using 3D point cloud technologies provides an opportunity to analyze spatial relationships of surfaces using orientation data. We present a MATLAB® script that produces planar geologic attitude data (e.g., strike, dip, and dip-direction data) from 3D datasets (e.g., point clouds, 3D scanning). The method utilizes Cartesian coordinates of triangular planar surfaces and converts them into matrices of conventional geologic attitude data. Spatial relationships among data points can be investigated, using polar tangent diagrams, stereographic analysis, or geologic curvature analysis. We utilize this script to create "synthetic" graphical plots (e.g., stereograms, tangent diagrams) from geomechanically realistic, virtual, folded surfaces produced by dynamic modeling. Synthetic graphical diagrams are of considerable usefulness in interpreting graphical plots (e.g., stereograms) of attitude data from natural folded rock surfaces, particularly in locations with poor exposure. â¢This script outputs attitude data (strike, dip, and dip direction) in a spreadsheet and as a text file for use in other visualization software.â¢A tangent diagram is created and displayed in this script for rapid visualization and fold shape assessment.â¢The MATLAB script is readily modified to accept multiple data formats for input (e.g., MATLAB variables, *.csv files, etc.) and output (e.g., *.csv files, *.txt files, etc.).
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Advancement in the field of computational research has made it possible for the in silico methods to offer significant benefits to both regulatory needs and requirements for risk assessments, and pharmaceutical industry to assess the safety profile of a chemical. Here, we present ProTox-II that incorporates molecular similarity, pharmacophores, fragment propensities and machine-learning models for the prediction of various toxicity endpoints; such as acute toxicity, hepatotoxicity, cytotoxicity, carcinogenicity, mutagenicity, immunotoxicity, adverse outcomes pathways (Tox21) and toxicity targets. The predictive models are built on data from both in vitro assays (e.g. Tox21 assays, Ames bacterial mutation assays, hepG2 cytotoxicity assays, Immunotoxicity assays) and in vivo cases (e.g. carcinogenicity, hepatotoxicity). The models have been validated on independent external sets and have shown strong performance. ProTox-II provides a freely available webserver for in silico toxicity prediction for toxicologists, regulatory agencies, computational and medicinal chemists, and all users without login at http://tox.charite.de/protox_II. The webserver takes a two-dimensional chemical structure as an input and reports the possible toxicity profile of the chemical for 33 models with confidence scores, and an overall toxicity radar chart along with three most similar compounds with known acute toxicity.
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Biologia Computacional , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Software , Humanos , Internet , Aprendizado de Máquina , Medição de RiscoRESUMO
There are at least two good reasons for the on-going interest in drug-target interactions: first, drug-effects can only be fully understood by considering a complex network of interactions to multiple targets (so-called off-target effects) including metabolic and signaling pathways; second, it is crucial to consider drug-target-pathway relations for the identification of novel targets for drug development. To address this on-going need, we have developed a web-based data warehouse named SuperTarget, which integrates drug-related information associated with medical indications, adverse drug effects, drug metabolism, pathways and Gene Ontology (GO) terms for target proteins. At present, the updated database contains >6000 target proteins, which are annotated with >330,000 relations to 196,000 compounds (including approved drugs); the vast majority of interactions include binding affinities and pointers to the respective literature sources. The user interface provides tools for drug screening and target similarity inclusion. A query interface enables the user to pose complex queries, for example, to find drugs that target a certain pathway, interacting drugs that are metabolized by the same cytochrome P450 or drugs that target proteins within a certain affinity range. SuperTarget is available at http://bioinformatics.charite.de/supertarget.
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Bases de Dados Factuais , Descoberta de Drogas , Redes e Vias Metabólicas/efeitos dos fármacos , Preparações Farmacêuticas/química , Proteínas/química , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacosRESUMO
During the development of methods for cancer diagnosis and treatment, a vast amount of information is generated. Novel cancer target proteins have been identified and many compounds that activate or inhibit cancer-relevant target genes have been developed. This knowledge is based on an immense number of experimentally validated compound-target interactions in the literature, and excerpts from literature text mining are spread over numerous data sources. Our own analysis shows that the overlap between important existing repositories such as Comparative Toxicogenomics Database (CTD), Therapeutic Target Database (TTD), Pharmacogenomics Knowledge Base (PharmGKB) and DrugBank as well as between our own literature mining for cancer-annotated entries is surprisingly small. In order to provide an easy overview of interaction data, it is essential to integrate this information into a single, comprehensive data repository. Here, we present CancerResource, a database that integrates cancer-relevant relationships of compounds and targets from (i) our own literature mining and (ii) external resources complemented with (iii) essential experimental and supporting information on genes and cellular effects. In order to facilitate an overview of existing and supporting information, a series of novel information connections have been established. CancerResource addresses the spectrum of research on compound-target interactions in natural sciences as well as in individualized medicine; CancerResource is available at: http://bioinformatics.charite.de/cancerresource/.
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Antineoplásicos/farmacologia , Bases de Dados de Proteínas , Proteínas de Neoplasias/metabolismo , Antineoplásicos/química , Linhagem Celular Tumoral , Mineração de Dados , Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Neoplasias/genética , Software , Integração de SistemasRESUMO
A vast number of sweet tasting molecules are known, encompassing small compounds, carbohydrates, d-amino acids and large proteins. Carbohydrates play a particularly big role in human diet. The replacement of sugars in food with artificial sweeteners is common and is a general approach to prevent cavities, obesity and associated diseases such as diabetes and hyperlipidemia. Knowledge about the molecular basis of taste may reveal new strategies to overcome diet-induced diseases. In this context, the design of safe, low-calorie sweeteners is particularly important. Here, we provide a comprehensive collection of carbohydrates, artificial sweeteners and other sweet tasting agents like proteins and peptides. Additionally, structural information and properties such as number of calories, therapeutic annotations and a sweetness-index are stored in SuperSweet. Currently, the database consists of more than 8000 sweet molecules. Moreover, the database provides a modeled 3D structure of the sweet taste receptor and binding poses of the small sweet molecules. These binding poses provide hints for the design of new sweeteners. A user-friendly graphical interface allows similarity searching, visualization of docked sweeteners into the receptor etc. A sweetener classification tree and browsing features allow quick requests to be made to the database. The database is freely available at: http://bioinformatics.charite.de/sweet/.
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Bases de Dados Factuais , Receptores Acoplados a Proteínas G/química , Edulcorantes/química , Aminoácidos/química , Sítios de Ligação , Carboidratos/química , Proteínas/química , Homologia Estrutural de ProteínaAssuntos
Cuidadores/psicologia , Crianças com Deficiência/psicologia , Assistência Domiciliar/psicologia , Atividades Cotidianas/psicologia , Adaptação Psicológica , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Crianças com Deficiência/reabilitação , Alemanha , Recursos em Saúde , Necessidades e Demandas de Serviços de Saúde , Pesquisa sobre Serviços de Saúde , Humanos , Lactente , Poder Familiar/psicologia , Relações Profissional-Família , Ajustamento Social , Apoio Social , Valores SociaisRESUMO
OBJECTIVES: Radiofrequency surgery is a minimally invasive technique for the treatment of the tongue base in sleep-disordered breathing. The aim of this study was to evaluate the changes in upper airway anatomy induced by radiofrequency surgery with MRI. STUDY DESIGN AND SETTING: 10 patients with sleep-disordered breathing were treated with radiofrequency surgery at tongue base. MRI measurements were performed before and after surgery with the help of a recently published protocol. RESULTS: The mean total number of energy delivered per patient was 4750 +/- 1641 Joule. Relevant changes could be observed neither for tongue volume or dimension nor for retrolingual space. CONCLUSIONS: Changes in upper airway anatomy could not be demonstrated. The effects of radiofrequency surgery of the tongue base may more likely be a result of changes in upper airway collapsibility. SIGNIFICANCE: Functional effects of surgical interventions in sleep-disordered breathing should be considered in addition to mechanistic concepts alone.
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Imageamento por Ressonância Magnética , Síndromes da Apneia do Sono/cirurgia , Língua/anatomia & histologia , Língua/cirurgia , Adulto , Idoso , Protocolos Clínicos , Eletrocirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Temperature controlled radiofrequency volumetric tissue reduction (RFVTR) of the tongue base is a minimally invasive technique for the treatment of obstructive sleep apnea. But despite its widespread use, little is yet known about in vivo effects in humans. Such knowledge would be essential for evidence-based criteria in the selection of energy application. METHODS: In a preparatory in vitro study, porcine tongues were preserved in growing medium. Lesions with different amounts of energy were applied, and maximum diameters were assessed. In the in vivo study, 11 patients were treated with RFVTR at the tongue base by employing different energy levels (800, 600, 400, or 200 J) on two application sites. Magnetic resonance imagery scans were performed 4 to 6, 8 to 10, and 24 hours after surgery. An inversion recovery technique was used to visualize the lesions. RESULTS: RFVTR created lesions at the porcine tongue from 50 J and higher. Maximum lesion sizes were achieved with 400 J. In vivo, all the lesions were clearly visible in the postoperative scans. Lesion size increased with the amount of energy applied. Maximum diameters were created from 600 J and higher. Higher amounts of energy only resulted in a slight increase in lesion length. CONCLUSIONS: The application of 600 J at 85 degrees C leads to optimal lesion sizes. Higher amounts of energy will not lead to a relevant increase in tissue necrosis. With regard to the time needed for application, 600 J appears to be the ideal adjustment for energy delivery in the treatment of the human tongue.