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INTRODUCTION: Abnormal QRS-T angles are prognostic markers for cardiovascular deaths including sudden cardiac death. They occur in â¼5-6% of population-based cohorts but in â¼20% of patients with diabetes. The mechanistic background, electrical activation and/or recovery disturbances, is not known and the topic of this study. METHODS: Applying Frank vectorcardiography (VCG) and simultaneously recorded scalar 12lead ECG, electrical activation and recovery of abnormal QRS-T angles were studied in 311 participants (5.4%) from a population-based cohort of 5796 women and men in the main Swedish CArdio-Pulmonary bio-Imaging Study (SCAPIS) in Gothenburg. Cut-off values for the peak and mean QRS-T angles were > 124° and > 119°, based on the >95th percentile among all 1080 participants in the pilot SCAPIS and reference values for normal directions (Q1-Q3) from 319 apparently healthy (30%) of them. RESULTS: Of 311 cases 17% had known cardiac disease. Deviations of QRS and QRSarea-vectors from reference limits (90%) were significantly more common than deviations of T- and Tarea-vectors (65%). Standard ECG signs suggested pathophysiology in 20%; left bundle branch block (LBBB) and voltage criteria for left ventricular hypertrophy being most frequent (9-10%) each. Sub-group analysis of the 30 with LBBB showed very large variability in vector directions. CONCLUSIONS: Our observations provide mechanistic insights about abnormal QRS-T angles of potential value for future prognostic and interventional studies. The results also have potential implications for LBB area pacing and the approach to left ventricular hypertrophy.
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Introduction The aberrant right subclavian artery (ARSA), also called as lusorian artery (LA) is a developmental anomaly that exists in conjunction with a right non-recurrent laryngeal nerve (NRLN) in almost all cases. The average prevalence of such a vascular variation is estimated as 1%, although, studies have reported very different population means. Up to date, there is no available data on the frequency of this pattern in the Hungarian population. It can be treated as an indirect marker of a NRLN. Any preoperative information on the course of the inferior laryngeal nerves can help surgeons reduce the risk of an iatrogenic injury during thyroidectomies, especially in an environment where access to intraoperative neuromonitoring is limited. Objectives The primary aims were to determine the prevalence of an ARSA, predict the existence of an NRLN in the Hungarian population, and provide demographic analysis. Methods A retrospective, computed tomography-based study was carried out. Demographic description and statistical analysis were provided where applicable. Detected anomalous vasculatures were visualized with 3D segmentation, and images were interpreted. Results The imaging database review identified three patients with ARSA out of 686 eligible recordings, resulting in a frequency of 0.437% in the study population. All three patients were female and had a retroesophageal LA. Two of them had a Kommerell's diverticulum. One patient had common carotid arteries with a single origin. Conclusions The frequency of an ARSA and a concomitant NRLN among Hungarians fits into the results of recent meta-analyses. Preoperative assessment of this anomaly may reduce vocal cord complication rates of thyroidectomies.
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To obtain the multiproxy paleoenvironmental dataset from southeast Great Hungarian Plain (GHP), 345 sediment samples were collected at one cm intervals from the cores retrieved from Tovisies bed paleochannel, and six samples were analyzed for 14C dates. The obtained radiocarbon dates were calibrated to calendar ages using the IntCal20 calibration curve. Bayesian statistics within the R bacon 2.5.8 age-depth modeling package were used to establish the age-depth model and it represented the time frame for the entire dataset. The obtained polymodal grain size distribution (GSD) data was unmixed into four EMs using the AnalySize v.1.2.0 algorithm, employing the built-in General Weibull function which helped explain the dynamicity of the endmembers' sedimentation process. To understand the alluviation history, the endmember abundances were correlated with LOI55, LOI950, and magnetic susceptibility. The dataset presented in this article could be of potential reuse for studying the spatial-temporal environmental changes and in geoarchaeological research, providing insights into how human societies adapted to environmental shifts across the southeast GHP.
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The volume of epicardial adipose tissue (EATV) is increased in type-2 diabetes (T2D), while its attenuation (EATA) appears to be decreased. Similar patterns have been suggested in pre-diabetes, but data is scarce. In both pre-diabetes and T2D, any independent role of EATV and EATA in disease development remains to be proven, a task complicated by their substantial co-variation with other anthropometrics, e.g. BMI, waist circumference, and abdominal visceral adipose tissue (VAT). EATV and EATA was quantified in computed tomography (CT) images in a population study (n = 1948) using an automatic technique. Data was available on BMI, waist circumference, abdominal visceral adipose tissue (VAT) area, insulin resistance (IR) and glucose tolerance, the latter ranging from normal (NGT), over pre-diabetes (impaired fasting glucose [IFG, n = 414] impaired glucose tolerance [IGT, n = 321] and their combination [CGI, n = 128]), to T2D. EATV was increased in pre-diabetes, T2D and IR in univariable analyses and when adjusting for BMI, however not when adjusting for waist or VAT. EATA was reduced in pre-diabetes, T2D and IR in univariable analyses and when adjusting for BMI and waist, however not when adjusting for VAT. Adjustment for other co-variates had little influence on the results. In conclusion, EATV is increased and EATA reduced in pre-diabetes, T2D and IR, however, significant co-variation with other anthropometrics, especially VAT, obscures their function in disease development. The current results do not exclude a pathophysiological role of epicardial fat, but future studies need to adjust for anthropometrics, or focus on the microenvironment within the pericardial sac.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/diagnóstico por imagem , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/epidemiologia , Tecido Adiposo/diagnóstico por imagem , Resistência à Insulina/fisiologia , Tomografia Computadorizada por Raios X , Glucose , Gordura Intra-Abdominal/diagnóstico por imagem , Índice de Massa CorporalRESUMO
To develop a fully automatic model capable of reliably quantifying epicardial adipose tissue (EAT) volumes and attenuation in large scale population studies to investigate their relation to markers of cardiometabolic risk. Non-contrast cardiac CT images from the SCAPIS study were used to train and test a convolutional neural network based model to quantify EAT by: segmenting the pericardium, suppressing noise-induced artifacts in the heart chambers, and, if image sets were incomplete, imputing missing EAT volumes. The model achieved a mean Dice coefficient of 0.90 when tested against expert manual segmentations on 25 image sets. Tested on 1400 image sets, the model successfully segmented 99.4% of the cases. Automatic imputation of missing EAT volumes had an error of less than 3.1% with up to 20% of the slices in image sets missing. The most important predictors of EAT volumes were weight and waist, while EAT attenuation was predicted mainly by EAT volume. A model with excellent performance, capable of fully automatic handling of the most common challenges in large scale EAT quantification has been developed. In studies of the importance of EAT in disease development, the strong co-variation with anthropometric measures needs to be carefully considered.
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Tecido Adiposo/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Pericárdio/diagnóstico por imagem , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/normas , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Software/normasRESUMO
We aimed to evaluate the prevalence of asthma and its associating environmental factors within a 6-12-year-old population. A cross-sectional, questionnaire-based study was conducted in primary schools located in the capital of Hungary; 3836 eligible parent-reported questionnaires were evaluated. Besides the International Study of Asthma and Allergies in Childhood (ISAAC) phase three core questions for asthma, the survey also assessed various potential risk factors. We introduced the umbrella term cumulative asthma as the union of physician-diagnosed asthma and current wheezing to estimate the lifetime prevalence of asthma. Current wheezing and physician-diagnosed asthma showed a frequency of 9.5% and 6.3%, respectively. They contributed to a cumulative asthma prevalence of 12.6% among the sampled population, with a girl-boy percentage of 37.4% to 62.6%. Air-pollution and weedy areas were associated with greater risk for asthma, while a suburban residence showed lesser odds. Indoor smoking, visible mold, and keeping a dog were defined as risk factors for asthma, while the presence of plants in the bedroom and pet rodents were associated with lower odds ratios. The consumption of fast food, beverages containing additives and margarine were significantly higher in asthmatics, while we found frequent sport activity and cereal intake associated with lower odds ratios for asthma. In this urban environment, we identified an increased asthma prevalence compared to some previously published studies, but the cross-sectional design and the different methodology did not permit us to draw timeframe-dependent conclusions.
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Asma , Hipersensibilidade , Animais , Asma/epidemiologia , Asma/etiologia , Estudos Transversais , Cães , Prevalência , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Oropharyngeal and nasopharyngeal specimens collected by swabbing are the pillars of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics. Commercially available rapid antigen tests and self-sampling polymerase chain reaction services have made specimen collection available anytime and anywhere in nonmedical settings. In this study, we report the case of a 45-year-old man who accidentally ingested a swab during self-performed SARS-CoV-2 rapid antigen testing. Imaging studies revealed an elongated foreign body in the stomach. Urgent gastroscopy confirmed the presence of the swabbing applicator in the gastric lumen, which was retrieved using a loop without any complications. Millions of SARS-CoV-2 tests are performed daily, of which an increasing proportion are performed by laypeople. Foreign bodies account for a particular set of complications, which can be avoided by cautious sampling and using the correct technique. Radiopaque labeling of instruments would be useful. Otherwise, rare serious events can occur that may require immediate medical interventions.
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PURPOSE: To evaluate two chest tomosynthesis (CTS) scoring systems for cystic fibrosis (CF), one system developed by Vult von Steyern et al. (VvS) and one system based on the Brody scoring system for high-resolution computed tomography (HRCT) (modified Brody (mB)). Brody scoring of HRCT was used as reference. METHODS: In conjunction with routine control HRCT at clinical follow-up, 10 consecutive adult CF patients underwent CTS for research purposes. Four radiologists scored the CTS examinations using the mB and VvS scoring systems. All scores were compared to the Brody HRCT scores. The agreement between the evaluated CTS scoring systems and the reference HRCT scoring system was determined using Spearman's rank correlation coefficient and the intraclass correlation coefficient (ICC). MAJOR FINDINGS: Spearman's rank correlation coefficient showed strong correlations between HRCT score and both the mB and the VvS CTS total scores (median rs = 0.81 and 0.85, respectively). The ICC showed strong correlation between the CTS scoring systems and the reference: 0.88 for mB and 0.85 for VvS scoring. The median time for scoring was 20 and 10 minutes for the mB and VvS scoring systems, respectively. CONCLUSIONS: Both evaluated CTS scoring systems correlate well with the reference standard Brody HRCT scoring. The VvS CTS scoring system has a shorter reading time, suggesting its advantage in clinical practice.
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Fibrose Cística , Adulto , Fibrose Cística/diagnóstico por imagem , Humanos , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
The present investigation is directed to phase transitions in the equimolar NiCoFeCrGa high entropy alloy, which is a mixture of face-centered cubic (FCC) and body-centered cubic (BCC) crystalline phases. The microstructure of the samples was investigated by using scanning electron microscopy (SEM), time-of-flight secondary ion mass spectroscopy (TOF-SIMS), transmission electron microscopy-based energy-dispersive spectroscopy (EDS) and electron energy loss spectroscopy (EELS), as well as X-ray diffraction (XRD) measurements. Based on the phases observed in different temperature ranges, a sequence of the phase transitions can be established, showing that in a realistic process, when freely cooling the sample with the furnace from high to room temperature, a microstructure having spinodal-like decomposition can also be expected. The elemental mapping and magnetic behaviors of this decomposed structure are also studied.
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Blunt trauma of the head can result in temporal bone fracture. Different classifications exist, but from a functional perspective, to distinguish otic capsule sparing and otic capsule disrupting fractures is superior to the classic nomenclature. Disruption of the otic capsule is often associated with sensorineural hearing loss, vestibular dysfunction, cerebrospinal leakage, or even intracranial consequences. Pneumolabyrinth describes the condition when air is enclosed within the inner ear. It is a result of a pathological communication between the labyrinth and the middle ear spaces that often occurs due to trauma. It is not a ubiquitous but obvious radiographic hallmark of otic capsule violation. The present case is about a young woman who suffered a temporal bone fracture that involved the right lateral semicircular canal. Multiplanar and segmentation images were generated to depict the pneumolabyrinth developed in the lateral semicircular canal. Despite the preserved hearing, vestibular dysfunction was registered during the video head impulse test and videonystagmography. Treatment of pneumolabyrinth after temporal bone fracture can be a matter of surgery or conservative therapy. In the present case, we preferred conservative therapy because of the absence of serious consequences. Nevertheless, timing and the type of therapeutic modality must be personalized.
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BACKGROUND: Digital tomosynthesis (DTS) might be a low-dose/low-cost alternative to computed tomography (CT). PURPOSE: To investigate DTS relative to CT for surveillance of incidental, solid pulmonary nodules. MATERIAL AND METHODS: Recruited from a population study, 106 participants with indeterminate solid pulmonary nodules on CT underwent surveillance with concurrently performed CT and DTS. Nodule size on DTS was assessed by manual diameter measurements and semi-automatic nodule segmentations were independently performed on CT. Measurement agreement was analyzed according to Bland-Altman with 95% limits of agreement (LoA). Detection of nodule volume change > 25% by DTS in comparison to CT was evaluated with receiver operating characteristics (ROC). RESULTS: A total of 81 nodules (76%) were assessed as measurable on DTS by two independent observers. Inter- and intra-observer LoA regarding change in average diameter were ± 2 mm. Calculation of relative volume change on DTS resulted in wide inter- and intra-observer LoA in the order of ± 100% and ± 50%. Comparing relative volume change between DTS and CT resulted in LoA of -58% to 67%. The area under the ROC curve regarding the ability of DTS to detect volumetric changes > 25% on CT was 0.58 (95% confidence interval [CI] = 0.40-0.76) and 0.50 (95% CI = 0.35-0.66) for the two observers. CONCLUSION: The results of the present study show that measurement variability limits the agreement between DTS and CT regarding nodule size change for small solid nodules.
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Neoplasias Pulmonares/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Projetos Piloto , Sensibilidade e Especificidade , Nódulo Pulmonar Solitário/patologia , Suécia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The study aimed to determine the prevalence and risk factors of allergic rhinitis and related comorbidities in school-age children in Budapest, capital of Hungary. Data and epidemiological studies on this disease are still limited. METHODS: A cross sectional study was conducted in 21 representative and randomly selected primary schools in 2019. International Study of Asthma and Allergies in Childhood-based questionnaires (n = 6869) inquiring about prevalence and related risk factors of allergic rhinitis were distributed to all parents. The data were characterised with standard descriptive statistics: frequencies (percentages) and means for categorical and quantitative data, respectively. RESULTS: 3836 of the questionnaires (1857 M/1979F) were completed. The prevalence of current allergic rhinitis was 29.3% (1043), physician-diagnosed allergic rhinitis was 9.7% (373), cumulative allergic rhinitis was 36.2% (1289) and current allergic rhinoconjunctivitis was 16.2% (577). The presence of physician diagnosed atopic disease-asthma (p < 0.0001, OR = 4.398, 95% CI 3.356-5.807), food allergy (p < 0.0001, OR = 2.594, 95% CI 1.995-3.378), and eczema (p < 0.0001, OR = 1.899, 95% CI 1.568-2.300)-were significantly related to an increased risk of cumulative allergic rhinitis. Significant factors associated with allergic rhinitis include male gender (p < 0.0001), family history of atopy (p < 0.0001), frequent upper respiratory tract infections (p < 0.0001), tonsillectomy (p = 0.0054), antibiotics given in the first year of life (p < 0.0001), paracetamol given in the first year of life (p = 0.0038), long-lasting common infections caused by viruses and/or bacteria before the appearance of the allergy (p < 0.0001), consumption of drinks containing preservatives or colourants (p = 0.0023), duration of living in Budapest (p = 0.0386), smoking at home (p = 0.0218), smoking at home in the first year of life (p = 0.0048), birds at home (p = 0.0119), birds at home in the first year of life (p = 0.0052), visible mould in the bedroom (p = 0.0139), featherbedding (p = 0.0126), frequent or constant heavy-vehicle traffic (p = 0.0039), living in a weedy area (p < 0.0001) and living in the vicinity of an air-polluting factory or mine (p = 0.0128). CONCLUSIONS: The prevalence of allergic rhinoconjunctivitis in 6-12-year-old children in Budapest is higher than reported for most of the surrounding European countries. While asthma (OR = 4.398) is the most significant comorbidity, environmental factors such as birds at home in the first year of life (OR = 2.394) and living in a weedy area (OR = 1.640) seem to be the most important factors associated with AR. Strategies for preventive measures should be implemented. TRIAL REGISTRATION NUMBER: KUT-19/2019. The study was approved by the Ethics Committee at Heim Pál National Pediatric Institute.
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PURPOSE: Iatrogenic atrial septal defect (IASD) after catheter ablation (CA) for atrial fibrillation (AF) due to transseptal puncture (TSP) can occur. The aim of this prospective study was to describe the incidence of IASD and to detect any cerebrovascular accident (CVA) after radiofrequency (RF) and cryoballoon (CB) CA. METHODS: Between July 2014 and September 2016, 94 patients (pts) (RF; 48, CB; 46, 30 (31.9%) women, mean age = 60 ± 9.7 years) with paroxysmal AF were enrolled who underwent CA procedure for the first time. During RF ablation a single (n = 30, 62.5%) or double (n = 18, 37.5%) TSP was performed. Transoesophageal echocardiography before the procedure and at the 3-month and 12-month follow-up (FU) was accomplished. During the FU period, we evaluated the occurrence of any postprocedural CVA. RESULTS: At the 3-month FU, IASD was detected in 17/94 (18.1%) pts; in 9/48 (18.8%) pts in the RF while in 8/46 (17.4%) pts in the CB group (p = 0.866), all of them with left-to-right shunt. In the RF group, 6/30 (20%) pts with a single TSP while 3/18 (16.7%) pts in the double TSP group had IASD (p = 0.780). 14/17 (82.4%) IASDs showed high spontaneous closure rate at the 12-month FU. None of the pts died or suffered from CVA. CONCLUSION: Persistent IASD can occur rather frequently following AF CA. No significant difference was observed between the RF and CB techniques concerning the presence of IASD at 3-month. IASDs showed a high spontaneous closure rate. No cerebral thromboembolic event was observed in the 12-month FU period.
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Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Criocirurgia/efeitos adversos , Comunicação Interatrial/etiologia , Doença Iatrogênica , Ecocardiografia Transesofagiana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
RATIONALE AND OBJECTIVES: Chest tomosynthesis has been suggested as a suitable alternative to CT for follow-up of pulmonary nodules. The aim of the present study was to investigate the possibility of detecting pulmonary nodule growth using chest tomosynthesis. MATERIALS AND METHODS: Simulated nodules with volumes of approximately 100 mm3 and 300 mm3 as well as additional versions with increasing volumes were created. The nodules were inserted into images from pairs of chest tomosynthesis examinations, simulating cases where the nodule had either remained stable in size or increased in size between the two imaging occasions. Nodule volume growths ranging from 11% to 252% were included. A simulated dose reduction was applied to a subset of the cases. Cases differing in terms of nodule size, dose level, and nodule position relative to the plane of image reconstruction were included. Observers rated their confidence that the nodules were stable in size or not. The rating data for the nodules that were stable in size was compared to the rating data for the nodules simulated to have increased in size using ROC analysis. RESULTS: Area under the curve values ranging from 0.65 to 1 were found. The lowest area under the curve values were found when there was a mismatch in nodule position relative to the reconstructed image plane between the two examinations. Nodule size and dose level affected the results. CONCLUSION: The study indicates that chest tomosynthesis can be used to detect pulmonary nodule growth. Nodule size, dose level, and mismatch in position relative to the image reconstruction plane in the baseline and follow-up examination may affect the precision.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador , Radiografia Torácica/métodos , Reprodutibilidade dos Testes , Carga TumoralRESUMO
INTRODUCTION: Antihistamines are easily accessible and cover the vast majority of the medical therapy of allergic rhinitis. However, their systemic administration may more frequently associate with their well-known side-effect, sedation, which is a serious problem in persons in safety-critical jobs such as aviation. We have a poor understanding whether a non-sedative antihistamine has an impact on vigilance when hypobaric hypoxia occurs during flight. METHODS: In this randomized, placebo-controlled, double-blind, cross-over study the effect of 20 mg bilastine was compared to 10 mg cetirizine and to placebo (20 mg pyridoxine) in 33 individuals at ground level and at 4,000 m altitude simulated in hypobaric chamber. Levels of vigilance, ultrashort memory, combined distributive attention, monotony tolerance and peripheral blood oxygen saturation (SpO2) were assessed. RESULTS: Bilastine did not impair the tested abilities in comparison with the control groups either at ground level or hypobaric hypoxia. Administration of cetirizine increased the number of errors at ground level. At the simulated altitude, already impaired results were additionally demonstrated with regards to the distributive attention test. CONCLUSIONS: From the two examined antihistamines, bilastine should be the preferred medication for by individuals who require constant attention and are exposed to hypobaric hypoxia.
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Benzimidazóis/efeitos adversos , Cetirizina/efeitos adversos , Cognição/efeitos dos fármacos , Antagonistas não Sedativos dos Receptores H1 da Histamina/efeitos adversos , Piperidinas/efeitos adversos , Adulto , Altitude , Antialérgicos/administração & dosagem , Antialérgicos/efeitos adversos , Câmaras de Exposição Atmosférica , Aviação , Benzimidazóis/administração & dosagem , Cetirizina/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Feminino , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Piperidinas/administração & dosagemRESUMO
Purpose To investigate the performance of digital tomosynthesis (DTS) for detection and characterization of incidental solid lung nodules. Materials and Methods This prospective study was based on a population study with 1111 randomly selected participants (age range, 50-64 years) who underwent a medical evaluation that included chest computed tomography (CT). Among these, 125 participants with incidental nodules 5 mm or larger were included in this study, which added DTS in conjunction with the follow-up CT and was performed between March 2012 and October 2014. DTS images were assessed by four thoracic radiologists blinded to the true number of nodules in two separate sessions according to the 5-mm (125 participants) and 6-mm (55 participants) cut-off for follow-up of incidental nodules. Pulmonary nodules were directly marked on the images by the readers and graded regarding confidence of presence and recommendation for follow-up. Statistical analyses included jackknife free-response receiver operating characteristic, receiver operating characteristic, and Cohen κ coefficient. Results Overall detection rate ranges of CT-proven nodules 5 mm or larger and 6 mm or larger were, respectively, 49%-58% and 48%-62%. Jackknife free-response receiver operating characteristics figure of merit for detection of CT-proven nodules 5 mm or larger and 6 mm or larger was 0.47 and 0.51, respectively, and area under the receiver operating characteristic curve regarding recommendation for follow-up was 0.62 and 0.65, respectively. Conclusion Routine use of DTS would result in lower detection rates and reduced number of small nodules recommended for follow-up. © RSNA, 2018.
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Neoplasias Pulmonares/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , SuéciaRESUMO
BACKGROUND: Postconditioning may prove to be a suitable method to decrease ischemia-reperfusion injury of intestine after mesenteric arterial occlusion. Toll-like-receptor-4 is involved in the pathophysiology of organ damage after ischemia-reperfusion; therefore, the aim of our study was to investigate the effect of postconditioning on the mucosal expression of toll-like-receptor-4. METHODS: Male Wistar rats (n = 10/group) underwent 60 minutes of superior mesenteric artery occlusion followed by 6 hours of reperfusion in 3 groups: sham-operated, ischemia-reperfusion, and a postconditioned group. Postconditioning was performed by 6 alternating cycles of 10 seconds of reperfusion/reocclusion. Blood and tissue samples were collected at the end of reperfusion. Intestinal histopathologic changes and immunohistochemical expression of mucosal caspase-3, antioxidant status, and protein levels of high-mobility group box-1 and toll-like-receptor-4 were assessed. Immunofluorescent labeling and confocal microscopic analysis of toll-like-receptor-4 were performed. Mucosal and serum levels of interleukin-6 and tumor necrosis factor-α protein were measured. RESULTS: Histologic alterations in the postconditioned group were associated with decreased caspase-3 positivity, less toll-like-receptor-4 mRNA, and less protein expression of high-mobility group box-1 and toll-like-receptor-4 in the intestinal villi compared with the ischemia-reperfusion group. Furthermore, a significantly improved antioxidant state of the intestinal mucosa and less mucosal and serum protein levels of interleukin-6 and tumor necrosis factor-α were detected in the postconditioned group. CONCLUSION: Small intestinal ischemia-reperfusion injury in male Wistar rats caused by the occlusion of the superior mesenteric artery was ameliorated by the use of postconditioning, showing a more favorable inflammatory response, which may be attributed to the decreased mucosal expression of toll-like-receptor-4.
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Pós-Condicionamento Isquêmico/métodos , Isquemia Mesentérica/patologia , Isquemia Mesentérica/terapia , Traumatismo por Reperfusão/prevenção & controle , Receptor 4 Toll-Like/metabolismo , Animais , Biomarcadores/sangue , Biópsia por Agulha , Western Blotting , Modelos Animais de Doenças , Imuno-Histoquímica , Mucosa Intestinal/irrigação sanguínea , Precondicionamento Isquêmico/efeitos adversos , Precondicionamento Isquêmico/métodos , Masculino , Microscopia Confocal , Distribuição Aleatória , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: In non-small cell lung cancer (NSCLC) KRAS-mutant status is a negative prognostic and predictive factor. Nitrogen-containing bisphosphonates inhibit prenylation of small G-proteins (e.g. Ras, Rac, Rho) and thus may affect proliferation and migration. In our preclinical work, we investigated the effect of an aminobisphosphonate compound (zoledronic acid) on mutant and wild type KRAS-expressing human NSCLC cell lines. RESULTS: We confirmed that zoledronic acid was unable to inhibit the prenylation of mutant K-Ras unlike in the case of wild type K-Ras. In case of in vitro proliferation, the KRAS-mutant human NSCLC cell lines showed resistance to zoledronic acid wild-type KRAS-cells proved to be sensitive. Combinatory application of zoledronic acid enhanced the cytostatic effect of cisplatin. Zoledronic acid did not induce significant apoptosis. In xenograft model, zoledronic acid significantly reduced the weight of wild type KRAS-EGFR-expressing xenograft tumor by decreasing the proliferative capacity. Futhermore, zoledronic acid induced VEGF expression and improved in vivo tumor vascularization. MATERIALS AND METHODS: Membrane association of K-Ras was examined by Western-blot. In vitro cell viability, apoptotic cell death and migration were measured in NSCLC lines with different molecular background. The in vivo effect of zoledronic acid was investigated in a SCID mouse subcutaneous xenograft model. CONCLUSIONS: The in vitro and in vivo inhibitory effect of zoledronic acid was based on the blockade of cell cycle in wild type KRAS-expressing human NSCLC cells. The zoledronic acid induced vascularization supported in vivo cytostatic effect. Our preclinical investigation suggests that patients with wild type KRAS-expressing NSCLC could potentially benefit from aminobisphosphonate therapy.
Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Difosfonatos/farmacologia , Imidazóis/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Células A549 , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Relação Dose-Resposta a Droga , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos SCID , Invasividade Neoplásica , Neovascularização Patológica , Fenótipo , Transdução de Sinais/efeitos dos fármacos , Carga Tumoral/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Ácido ZoledrônicoRESUMO
Recent findings indicate a strong correlation between the risk of future heart disease and the volume of adipose tissue inside of the pericardium. So far, large-scale studies have been hindered by the fact that manual delineation of the pericardium is extremely time-consuming and that existing methods for automatic delineation lack accuracy. An efficient and fully automatic approach to pericardium segmentation and epicardial fat volume (EFV) estimation is presented, based on a variant of multi-atlas segmentation for spatial initialization and a random forest classifier for accurate pericardium detection. Experimental validation on a set of 30 manually delineated computer tomography angiography volumes shows a significant improvement on state-of-the-art in terms of EFV estimation [mean absolute EFV difference: 3.8 ml (4.7%), Pearson correlation: 0.99] with run times suitable for large-scale studies (52 s). Further, the results compare favorably with interobserver variability measured on 10 volumes.