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1.
Haematologica ; 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31289207

RESUMO

Hereditary pulmonary alveolar proteinosis due to GM-CSF receptor deficiency (herPAP) constitutes a life-threatening lung disease characterized by alveolar deposition of surfactant protein secondary to defective alveolar macrophage function. As current therapeutic options are primarily symptomatic, we have explored the potential of hematopoietic stem cell-based gene therapy. Using Csf2rb-/- mice, a model closely reflecting the human herPAP disease phenotype, we here demonstrate robust pulmonary engraftment of an alveolar macrophage population following intravenous transplantation of lentivirally corrected hematopoietic stem and progenitor cells. Engraftment was associated with marked improvement of critical herPAP disease parameters, including bronchoalveolar fluid protein, cholesterol and cytokine levels, pulmonary density on CT scans, pulmonary deposition of Periodic Acid-Schiff+ material as well as respiratory mechanics. These effects were stable for at least nine months. With respect to engraftment and alveolar macrophage differentiation kinetics, we demonstrate the rapid development of CD11c+Siglec-F+ cells in the lungs from a CD11c-/Siglec-F+ progenitor population within four weeks after transplantation. Based on these data, we suggest hematopoietic stem cell-based gene therapy as an effective and cause-directed treatment approach for herPAP.

2.
J Magn Reson Imaging ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31276264

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality. Identification of imaging biomarkers for phenotyping is necessary for future treatment and therapy monitoring. However, translation of visual analytic pipelines into clinics or their use in large-scale studies is significantly slowed by time-consuming postprocessing steps. PURPOSE: To implement an automated tool chain for regional quantification of pulmonary microvascular blood flow in order to reduce analysis time and user variability. STUDY TYPE: Prospective. POPULATION: In all, 90 MRI scans of 63 patients, of which 31 had a COPD with a mean Global Initiative for Chronic Obstructive Lung Disease status of 1.9 ± 0.64 (µ ± σ). FIELD STRENGTH/SEQUENCE: 1.5T dynamic gadolinium-enhanced MRI measurement using 4D dynamic contrast material-enhanced (DCE) time-resolved angiography acquired in a single breath-hold in inspiration. [Correction added on August 20, 2019, after first online publication: The field strength in the preceding sentence was corrected.] ASSESSMENT: We built a 3D convolutional neural network for semantic segmentation using 29 manually segmented perfusion maps. All five lobes of the lung are denoted, including the middle lobe. Evaluation was performed on 61 independent cases from two sites of the Multi-Ethnic Study of Arteriosclerosis (MESA)-COPD study. We publish our implementation of a model-free deconvolution filter according to Sourbron et al for 4D DCE MRI scans as open source. STATISTICAL TEST: Cross-validation 29/61 (# training / # testing), intraclass correlation coefficient (ICC), Spearman ρ, Pearson r, Sørensen-Dice coefficient, and overlap. RESULTS: Segmentations and derived clinical parameters were processed in ~90 seconds per case on a Xeon E5-2637v4 workstation with Tesla P40 GPUs. Clinical parameters and predicted segmentations exhibit high concordance with the ground truth regarding median perfusion for all lobes with an ICC of 0.99 and a Sørensen-Dice coefficient of 93.4 ± 2.8 (µ ± σ). DATA CONCLUSION: We present a robust end-to-end pipeline that allows for the extraction of perfusion-based biomarkers for all lung lobes in 4D DCE MRI scans by combining model-free deconvolution with deep learning. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019.

4.
J Clin Immunol ; 39(1): 45-54, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30547383

RESUMO

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.

5.
Stem Cell Reports ; 11(3): 696-710, 2018 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-30100408

RESUMO

Induced pluripotent stem cell (iPSC)-derived hematopoietic cells represent a highly attractive source for cell and gene therapy. Given the longevity, plasticity, and self-renewal potential of distinct macrophage subpopulations, iPSC-derived macrophages (iPSC-Mφ) appear of particular interest in this context. We here evaluated the airway residence, plasticity, and therapeutic efficacy of iPSC-Mφ in a murine model of hereditary pulmonary alveolar proteinosis (herPAP). We demonstrate that single pulmonary macrophage transplantation (PMT) of 2.5-4 × 106 iPSC-Mφ yields efficient airway residence with conversion of iPSC-Mφ to an alveolar macrophage (AMφ) phenotype characterized by a distinct surface marker and gene expression profile within 2 months. Moreover, PMT significantly improves alveolar protein deposition and other critical herPAP disease parameters. Thus, our data indicate iPSC-Mφ as a source of functional macrophages displaying substantial plasticity and therapeutic potential that upon pulmonary transplantation will integrate into the lung microenvironment, adopt an AMφ phenotype and gene expression pattern, and profoundly ameliorate pulmonary disease phenotypes.

6.
PLoS One ; 13(2): e0191457, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29408869

RESUMO

OBJECTIVES: Among patients with non-cystic fibrosis bronchiectasis, 1-18% have an underlying diagnosis of primary ciliary dyskinesia (PCD) and it is suspected that there is under-recognition of this disease. Our intention was to evaluate the specific features of PCD seen on computed tomography (CT) in the cohort of bronchiectasis in order to facilitate the diagnosis. MATERIALS AND METHODS: One hundred and twenty-one CTs performed in patients with bronchiectasis were scored for the involvement, type, and lobar distribution of bronchiectasis, bronchial dilatation, and bronchial wall thickening. Later, associated findings such as mucus plugging, tree in bud, consolidations, ground glass opacities, interlobular thickening, intralobular lines, situs inversus, emphysema, mosaic attenuation, and atelectasis were registered. Patients with PCD (n = 46) were compared to patients with other underlying diseases (n = 75). RESULTS: In patients with PCD, the extent and severity of the bronchiectasis and bronchial wall thickness were significantly lower in the upper lung lobes (p<0.001-p = 0.011). The lobar distribution differed significantly with a predominance in the middle and lower lobes in patients with PCD (<0.001). Significantly more common in patients with PCD were mucous plugging (p = 0.001), tree in bud (p <0.001), atelectasis (p = 0.009), and a history of resection of a middle or lower lobe (p = 0.047). Less common were emphysematous (p = 0.003) and fibrotic (p<0.001) changes. A situs inversus (Kartagener's Syndrome) was only seen in patients with PCD (17%, p <0.001). CONCLUSION: Typical imaging features in PCD include a predominance of bronchiectasis in the middle and lower lobes, severe tree in bud pattern, mucous plugging, and atelectasis. These findings may help practitioners to identify patients with bronchiectasis in whom further work-up for PCD is called for.


Assuntos
Transtornos da Motilidade Ciliar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Rofo ; 189(11): 1076-1085, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28934808

RESUMO

Purpose New teaching formats are required to implement competency-based teaching in radiology teaching. Therefore, we have established and evaluated two practical competency-based radiological courses. Materials and Methods The courses were held in a multimedia room with 25 computers and a professional DICOM viewer. Students were taught basic image analysis and presented clinical cases with a DICOM viewer under supervision of an instructor using desktop monitoring software. Two courses (elective course and obligatory course) were evaluated by the students (n = 160 and n = 100) and instructors (n = 9) using an anonymized online survey. Results Courses were evaluated positively by the students and instructors. From the perspective of the students, the courses increased understanding of cross-sectional anatomy (elective/obligatory course: 97 %/95 %) and radiologic findings (97 %/99 %). Furthermore, the course increased the students' interest in radiology (61 %/65 %). The students considered this way of teaching to be relevant to their future occupation (92 % of students in the obligatory course). The higher incidence of teacher-student interaction and the possibility of independent image analysis were rated positively. The majority of instructors did not observe increased distractibility due to the computers (67 %) or notice worse preparation for MC tests (56 %). However, 56 % of instructors reported greater preparation effort. Conclusion Practical competency-based radiological teaching using a DICOM viewer is a feasible innovative approach with high acceptance among students and instructors. It fosters competency-based learning as proposed by the model curriculum of the German Radiological Society (DRG) and the National Competency-based Catalogue of Learning Objectives for Undergraduate Medical Education (NKLM). Key Points · Practical competency-based radiological teaching is highly accepted by students and instructors.. · Students report improved understanding of imaging anatomy and radiological findings.. · Interactive case presentation with a DICOM viewer fosters competency-based learning.. Citation Format · Koestner W, Otten W, Kaireit T et al. Competency-Based Teaching in Radiology - Implementation and Evaluation of Interactive Workstation-Based Learning to Apply NKLM-Based Content. Fortschr Röntgenstr 2017; 189: 1076 - 1085.


Assuntos
Educação Baseada em Competências/métodos , Instrução por Computador/métodos , Radiologia/educação , Estudantes de Medicina/estatística & dados numéricos , Interface Usuário-Computador , Competência Clínica/estatística & dados numéricos , Educação Baseada em Competências/estatística & dados numéricos , Instrução por Computador/estatística & dados numéricos , Diagnóstico por Imagem/estatística & dados numéricos , Avaliação Educacional/estatística & dados numéricos , Alemanha , Ensino
8.
Rofo ; 189(10): 967-976, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28697528

RESUMO

Purpose Aim of our study was to evaluate the motivation of medical students in their final year of medical school to choose radiology for further specialization by means of a Germany-wide survey. Materials and Methods The survey was performed during the 2015/16 semester among German medical students in their four months radiology elective during the final year. Invitations for the study were distributed by the Student Secretariats of each university. The survey was web-based with EvaSys 7.0 software. Questions on radiology contents during medical studies and "practical year" were part of the survey. Plans for residency and possible advantages and disadvantages of radiology as medical specialty were inquired. Descriptive statistics and group comparisons were used as analysis methods. Results 89 students participated in the survey at the beginning and 60 students at the end of the practical year. Of these 39 students could be identified who answered both questionnaires. Most students were satisfied with their final year radiology elective (mean 1.8 on a range from 1 to 5). Nevertheless, they criticized mentoring during routine work (mean 2.1) and a lack of educational courses (mean 2.1). Most students (83 %) were uncertain about their residency choice at the beginning of their "practical year" and about one fifth changed their plans. From the students' point of view main advantages of radiology included contact with many other clinical disciplines (87 %) and the working conditions (68 %). The reduced patient contact (42 %), the large amount of work at a computer (43 %), and the dependency on referring physicians (42 %) were regarded as the main disadvantages. The students regarded the way radiology is taught during the studies as not practical enough. With regard to radiology the majority of students (63 %) felt poorly prepared for their future work. Conclusion The "practical year" is important regarding the choice of future specialization. There was a high degree of satisfaction with the "practical year" in radiology. The mentoring during routine work and a lack of educational courses was mildly criticized. These factors provide room for improvement to foster students' interest in radiology. Key Points · The "practical year" is important regarding the choice of further specialization.. · Criticisms of radiology in the "practical year" were mentoring and courses.. · Students feel poorly prepared for their future work regarding practical radiological skills.. Citation Format · Dettmer S, Fischer V, Paeßens C et al. Who will be the Radiologists of Tomorrow? A survey of radiology during the "Practical Year" in Germany. Fortschr Röntgenstr 2017; 189: 967 - 976.


Assuntos
Escolha da Profissão , Radiologistas/estatística & dados numéricos , Radiologistas/tendências , Radiologia/educação , Estudantes de Medicina/estatística & dados numéricos , Inquéritos e Questionários , Adulto , Feminino , Alemanha , Humanos , Masculino , Radiologistas/classificação , Radiologia/tendências , Recursos Humanos , Adulto Jovem
9.
Eur J Radiol ; 94: 78-84, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28647206

RESUMO

PURPOSE: To describe early signs for restrictive subtype of chronic lung allograft dysfunction (CLAD) after lung transplantation in computed tomography (CT) and to evaluate the predictive value for disease progression and survival. MATERIAL AND METHODS: 52 CT examinations in lung transplant patients at CLAD onset were scored for CT features referring to airways disease, parenchymal or pleural abnormality. Patients with and without later development of restrictive CLAD (TLC≤80%) were compared. A radiological score for inflammation including pleural effusion, central and peripheral ground glass opacities and consolidations was calculated and used for survival analysis. RESULTS: CT of patients with later development of restrictive CLAD showed significantly more often abnormalities at CLAD onset, in particular consolidations (57% vs. 4%; p<0.001) and ground glass attenuations (71% vs. 7%; p<0.001) than those of patients without the restrictive phenotype. CT score for inflammation was significantly higher in patients with than without later restrictive CLAD (3.4 vs. 0.6; p<0.001). Survival of patients with a high score (>2) for inflammation in CT at CLAD onset was significantly lower than of those with a low score (443 vs. 2415 days; p=0.019). CONCLUSIONS: CT at CLAD onset differs in patients with/without later development of the restrictive phenotype. It is therefore an indicator for future development of restrictive CLAD and predictor for survival. It should be implemented in the diagnostic work-up at diagnosis of CLAD.


Assuntos
Pneumopatias/diagnóstico por imagem , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Progressão da Doença , Feminino , Seguimentos , Humanos , Pneumopatias/mortalidade , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Disfunção Primária do Enxerto/mortalidade , Disfunção Primária do Enxerto/fisiopatologia , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos
10.
Acta Radiol Open ; 6(2): 2058460117694216, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28321331

RESUMO

BACKGROUND: Targeted therapies are the standard treatment in patients with metastatic renal cell carcinoma (mRCC) and are known to cause adverse pulmonary events. Organizing pneumonia (OP) with its various manifestations in computed tomography (CT) has therefore lately received more attention. PURPOSE: To describe the spectrum of CT patterns of OP in patients with mRCC receiving targeted therapies. MATERIAL AND METHODS: Seventeen patients with known therapy-related OP were analyzed retrospectively by two blinded radiologists in consensus. Images were scored according to OP patterns that have previously been described. Additionally, the distribution and the predominant imaging pattern in each patient were determined. RESULTS: In our cohort, ground glass opacity was the most common imaging pattern (17/17, 100%) in patients with OP followed by a reticular pattern (12/17, 71%), consolidations (10/17, 59%), nodules (7/17, 41%), crazy paving (5/17, 29%), bronchi(ol)ectasis (4/17, 24%), focal mass (3/17, 18%), and reversed halo (1/17, 6%). The most common imaging pattern was changing multifocal consolidations (8/17, 47%). A bronchocentric and a nodular pattern were found in four patients (24%) each, a progressive fibrotic pattern in none patient, and reversed halo/atoll pattern in one (6%) case. CONCLUSION: OP is the major differential diagnosis to be considered in patients with targeted therapies and pulmonary changes. Knowledge of the variety of imaging findings can facilitate diagnosis.

11.
PLoS One ; 10(10): e0139102, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26430890

RESUMO

To determine whether density mapping (DM) is more accurate for detection and quantification of pathologic air trapping (pAT) in patients after lung transplantation compared to other CT air trapping measures. One-hundred forty-seven lung and heart-lung transplant recipients underwent CT-examinations at functional residual capacity (FRC) and total lung capacity (TLC) and PFT six months after lung transplantation. Quantification of air trapping was performed with the threshold-based method in expiration (EXP), density mapping (DM) and the expiratory to inspiratory ratio of the mean lung density (E/I-ratio MLD). A non-rigid registration of inspiration-expiration CT-data with a following voxel-to-voxel mapping was carried out for DM. Systematic variation of attenuation ranges was performed for EXP and DM and correlated with the ratio of residual volume to total lung capacity (RV/TLC) by Spearman rank correlation test. AT was considered pathologic if RV/TLC was above the 95th percentile of the predicted upper limit of normal values. Receiver operating characteristic (ROC) analysis was performed. The optimal attenuation range for the EXP method was from -790 HU to -950 HU (EXP(-790 to -950HU)) (r = 0.524, p<0.001) to detect air trapping. Within the segmented lung parenchyma, AT was best defined as voxel difference less than 80 HU between expiration and registered inspiration using the DM method. DM correlated best with RV/TLC (r = 0.663, p<0.001). DM and E/I-ratio MLD showed a larger AUC (0.78; 95% CI 0.69-0.86; 0.76, 95% CI 0.67-0.85) than EXP(-790 HU to -950 HU) (0.71, 95% CI 0.63-0.78). DM and E/I-ratio MLD showed better correlation with RV/TLC and are more suited quantitative CT-methods to detect pAT in lung transplant patients than the EXP(-790HU to -950HU).


Assuntos
Transplante de Pulmão , Pulmão/patologia , Adulto , Ar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Tomografia Computadorizada por Raios X
12.
PLoS One ; 9(4): e93783, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24713820

RESUMO

OBJECTIVES: To prospectively evaluate quantitative airway wall measurements of thin-section CT for the diagnosis of Bronchiolitis Obliterans Syndrome (BOS) following lung transplantation. MATERIALS AND METHODS: In 141 CT examinations, bronchial wall thickness (WT), the wall area percentage (WA%) calculated as the ratio of the bronchial wall area and the total area (sum of bronchial wall area and bronchial lumen area) and the difference of the WT on inspiration and expiration (WTdiff) were automatically measured in different bronchial generations. The measurements were correlated with the lung function parameters. WT and WA% in CT examinations of patients with (n = 25) and without (n = 116) BOS, were compared using the unpaired t-test and univariate analysis of variance, while also considering the differing lung volumes. RESULTS: Measurements could be performed in 2,978 bronchial generations. WT, WA%, and WTdiff did not correlate with the lung function parameters (r<0.5). The WA% on inspiration was significantly greater in patients with BOS than in patients without BOS, even when considering the dependency of the lung volume on the measurements. WT on inspiration and expiration and WA% on expiration did not show significant differences between the groups. CONCLUSION: WA% on inspiration was significantly greater in patients with than in those without BOS. However, WA% measurements were significantly dependent on lung volume and showed a high variability, thus not allowing the sole use of bronchial wall measurements to differentiate patients with from those without BOS.


Assuntos
Brônquios/patologia , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/patologia , Adolescente , Adulto , Idoso , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/fisiopatologia , Feminino , Humanos , Pulmão/patologia , Pulmão/fisiopatologia , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testes de Função Respiratória , Tomografia Computadorizada por Raios X , Adulto Jovem
13.
Laryngoscope ; 124(3): 751-4, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23832771

RESUMO

OBJECTIVE/HYPOTHESIS: Magnetic resonance imaging of the temporal bone has an important role in decision making with regard to cochlea implantation, especially in children with cochlear nerve deficiency. The purpose of this study was to evaluate the usefulness of the combination of an advanced high-resolution T2-weighted sequence with a surface coil in a 3-Tesla magnetic resonance imaging scanner in cases of suspected cochlear nerve aplasia. STUDY DESIGN: Prospective study. METHODS: Seven patients with cochlear nerve hypoplasia or aplasia were prospectively examined using a high-resolution three-dimensional variable flip-angle turbo spin-echo sequence using a surface coil, and the images were compared with the same sequence in standard resolution using a standard head coil. Three neuroradiologists evaluated the magnetic resonance images independently, rating the visibility of the nerves in diagnosing hypoplasia or aplasia. RESULTS: Eight ears in seven patients with hypoplasia or aplasia of the cochlear nerve were examined. The average age was 2.7 years (range, 9 months-5 years). Seven ears had accompanying malformations. The inter-rater reliability in diagnosing hypoplasia or aplasia was greater using the high-resolution three-dimensional variable flip-angle turbo spin-echo sequence (fixed-marginal kappa: 0.64) than with the same sequence in lower resolution (fixed-marginal kappa: 0.06). CONCLUSIONS: Examining cases of suspected cochlear nerve aplasia using the high-resolution three-dimensional variable flip-angle turbo spin-echo sequence in combination with a surface coil shows significant improvement over standard methods.


Assuntos
Nervo Coclear/anormalidades , Anormalidades Congênitas/patologia , Imagem Ecoplanar/métodos , Perda Auditiva Neurossensorial/diagnóstico , Pré-Escolar , Implante Coclear/métodos , Estudos de Coortes , Anormalidades Congênitas/cirurgia , Imagem Ecoplanar/instrumentação , Feminino , Perda Auditiva Neurossensorial/cirurgia , Humanos , Imagem Tridimensional , Lactente , Imagem por Ressonância Magnética/métodos , Masculino , Variações Dependentes do Observador , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Melhoria de Qualidade
14.
Transplantation ; 95(8): 1045-50, 2013 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-23591728

RESUMO

BACKGROUND: Advanced chronic lung allograft dysfunction limits survival after lung transplantation. We hypothesize that patients with chronic lung allograft dysfunction can be subdivided by exercise tolerance in two groups, and quality of life (QOL) and survival differ between the groups. METHODS: A single-center, cross-sectional, partly prospective, study was performed in our outpatient clinic between July and November 2011, including all patients with a forced expiratory volume in 1 s <50% baseline. Respiratory parameters, 6-min walk test, and QOL were measured. Patients with low exercise capacity were defined as 6-min walk test <50% predicted or use of rollator or wheelchair. RESULTS: Fifty-two patients consented to participating in the study and 22 demonstrated low exercise capacity. These patients had pathologic respiratory muscle function (P=0.005) and decreased inspiratory capacity (IC; P=0.001). QOL was significantly reduced. Multivariate analysis proved that low IC (hazard ratio, 17.9; 95% confidence interval, 2.8-111; P=0.002) and increased P0.1/Pimax (hazard ratio, 7.1; 95% confidence interval, 1.4-35.8; P=0.016) were independently associated with decrease exercise capacity. CONCLUSION: Heterogeneity of patients with advanced lung allograft dysfunction regarding exercise tolerance might result from altered IC and impaired respiratory muscle function.


Assuntos
Tolerância ao Exercício/fisiologia , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/fisiologia , Adulto , Estudos Transversais , Teste de Esforço , Volume Expiratório Forçado/fisiologia , Humanos , Capacidade Inspiratória/fisiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Músculos Respiratórios/fisiopatologia , Caminhada , Trabalho Respiratório/fisiologia
15.
J Cardiothorac Surg ; 7: 51, 2012 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-22672731

RESUMO

BACKGROUND: At present only few studies directly compare the diagnostic yield of endobronchial ultrasound guided fine needle aspiration (EBUS-FNA) and transcervical video-assisted mediastinoscopy (TM) for mediastinal lymph node staging in patients with NSCLC. If and when EBUS-FNA may replace TM as Gold Standard remains controversial. METHODS: From April 2008 to December 2009, 36 patients with mediastinal lymphadenopathy underwent simultaneous EBUS-FNA/ TM at our institution. Among them were 26 patients with confirmed or suspected NSCLC. RESULTS: A total of 133 samples were obtained by EBUS-FNA and 157 samples by TM. EBUS-FNA achieved significantly less conclusive, but more indeterminate pathological results in comparison to TM (78.7% vs. 98.6%, p < 0.001; 14.9% vs. 1.4%, p = 0.007). Less paratracheal nodes were sampled by EBUS-FNA (right: 46.2% vs. 88.5%, p = 0.003; left: 23.1% vs. 65.4%, p = 0.005), while sampling rates in the subcarinal localisation were comparable (96.2% vs. 80.8%, p = NS). Among patients with confirmed NSCLC and conclusive EBUS-FNA/ TM findings (n = 18), the prevalence of N2/N3 disease was 66.7% (n = 12) according to TM findings. Diverging nodal stages were found in five patients (27.8%). Three patients who were N2 negative in EBUS-FNA were upstaged to N2 or N3 by TM, two patients with N2 status in EBUS-FNA were upstaged to N3 by TM. CONCLUSIONS: Compared to TM, EBUS-FNA had a lower diagnostic yield and resulted in systematic mediastinal nodal understaging. At this point we suggest corroborating negative EBUS-FNA results by transcervical mediastinoscopy.


Assuntos
Biópsia por Agulha Fina/métodos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Mediastinoscopia/métodos , Ultrassonografia de Intervenção/métodos , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Estudos Prospectivos , Cirurgia Vídeoassistida
16.
J Exp Clin Cancer Res ; 31: 15, 2012 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-22348342

RESUMO

BACKGROUND: SPC-c-Raf-1-BxB transgenic mice develop genetically induced disseminated lung adenocarcinoma allowing examination of carcinogenesis and evaluation of novel treatment strategies. We report on assessment of lung tumour growth kinetics using a semiautomated region growing segmentation algorithm. METHODS: 156 non contrast-enhanced respiratory gated micro-CT of the lungs were obtained in 12 SPC-raf transgenic (n = 9) and normal (n = 3) mice at different time points. Region-growing segmentation of the aerated lung areas was obtained as an inverse surrogate for tumour burden. Time course of segmentation volumes was assessed to demonstrate the potential of the method for follow-up studies. RESULTS: Micro-CT allowed assessment of tumour growth kinetics and semiautomated region growing enabled quantitative analysis. Significant changes of the segmented lung volumes over time could be shown (p = 0.009). Significant group differences could be detected between transgenic and normal animals for time points 8 to 13 months (p = 0.043), when marked tumour progression occurred. CONCLUSION: The presented region-growing segmentation algorithm allows in-vivo quantification of multifocal lung adenocarcinoma in SPC-raf transgenic mice. This enables the assessment of tumour load and progress for the study of carcinogenesis and the evaluation of novel treatment strategies.


Assuntos
Adenocarcinoma/genética , Transformação Celular Neoplásica , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-raf/genética , Proteína C Associada a Surfactante Pulmonar/genética , Microtomografia por Raio-X/métodos , Adenocarcinoma/patologia , Animais , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Transgênicos , Regiões Promotoras Genéticas
17.
Transplantation ; 93(2): 230-5, 2012 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-22129764

RESUMO

BACKGROUND: An obstructive pattern in pulmonary function test is common after lung transplantation (LTx) and may be caused by multiple disorders. In this study, the impact and outcome of an obstructive spirometric pattern identified in transplant recipients early posttransplantation were investigated. METHODS: Analyzing all patients undergoing double LTx between September 1, 2007, and October 1, 2009, we separated patients with an obstructive (forced expiratory volume in 1 sec [FEV(1)]: vital capacity [VC] <0.7) and a nonobstructive pattern (FEV(1):VC ≥0.7) in pulmonary function tests 3 months after transplantation. Pulmonary function measurement, bronchoscopy, laboratory parameter, computed tomography morphology, mortality, and bronchiolitis obliterans syndrome (BOS)-free survival were analyzed up to 36 months after transplantation. In addition, information about donor lungs were collected (age, smoking history, and blood gas before lung harvesting). RESULTS: From 122 recipients included, 17 (14%) exhibited an obstructive pattern. Recipients with an early obstructive pattern were older at transplantation, had significantly decreased FEV(1), increased total lung capacity, and donor organ with lower pO(2) when ventilated with 100% oxygen before retrieval. Obstructive patients developed their best FEV(1) earlier after LTx and demonstrated a significant increase in BOS development (47% vs. 14%). CONCLUSIONS: An obstructive lung function pattern early after LTx was associated with earlier development of BOS and may have negative impact on outcome after double LTx. Early obstructive pattern after transplantation might be an indication of structural donor lung injury.


Assuntos
Pneumopatias Obstrutivas/etiologia , Pneumopatias Obstrutivas/fisiopatologia , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/fisiologia , Adulto , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/fisiopatologia , Feminino , Seguimentos , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Espirometria , Fatores de Tempo , Doadores de Tecidos , Capacidade Vital
18.
Behav Brain Res ; 216(2): 712-8, 2011 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-20887754

RESUMO

The underlying mechanisms controlling food intake and satiety are thoroughly controlled, but seem to be insufficient under conditions of almost unlimited food supply. Hence, overweight and obesity are serious problems especially in industrialized countries. To assess the possible influence of CD26, exerting a dipeptidyl peptidase activity (DPP4) cleaving several energy homeostasis-relevant peptides, we investigated wild type and DPP4-deficient dark agouti rats in a model of diet-induced obesity and found a reduced weight gain in DPP4-deficient rats. When investigating the specific increase of whole body fat volume by MRI to assess the distribution pattern (subcutaneous vs. intraabdominal), there was an altered ratio under dietary conditions only in DPP4-deficient rats, which was due to lower intraabdominal fat amounts. Furthermore, we investigated the number of cells immunopositive for the leptin receptor (OB-R), the orexigenic leptin antagonist neuropeptide Y (NPY), as well as of the NPY receptors Y1, Y2, and Y5 within hypothalamic nuclei. Independent from the body weight, higher levels of NPY and all receptors were expressed in DPP4-deficent rats. Under obese conditions, hypothalamic Y2-levels were reduced in both strains. Concerning NPY and Y1, there were partly oppositional effects, with reduced hypothalamic Y1 levels only in wild types, and increased NPY levels only in DPP4-deficient rats. These effects might be responsible for unaltered food intake in DPP4-deficent rats compared to wild types, despite reduced weight gain. However, since the food intake remained unaffected, these effects suggest that DPP4 exerts its effects on intraabdominal fat also via peripheral actions.


Assuntos
Dipeptidil Peptidase 4/deficiência , Gordura Intra-Abdominal/fisiologia , Neuropeptídeo Y/metabolismo , Obesidade/enzimologia , Ganho de Peso/genética , Animais , Regulação do Apetite/genética , Regulação do Apetite/fisiologia , Gorduras na Dieta/metabolismo , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/fisiologia , Modelos Animais de Doenças , Ingestão de Energia/genética , Técnicas de Inativação de Genes , Masculino , Obesidade/genética , Obesidade/metabolismo , Ratos , Ratos Endogâmicos , Receptores de Neuropeptídeo Y/metabolismo , Ganho de Peso/fisiologia
19.
Respir Res ; 11: 181, 2010 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-21176193

RESUMO

BACKGROUND: Micro-computed tomography (micro-CT) is a novel tool for monitoring acute and chronic disease states in small laboratory animals. Its value for assessing progressive lung fibrosis in mice has not been reported so far. Here we examined the importance of in vivo micro-CT as non-invasive tool to assess progression of pulmonary fibrosis in mice over time. METHODS: Pulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-ß1 (AdTGF-ß1). Respiratory gated and ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary adenoviral gene or control vector delivery, and were then correlated with respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice. Visual assessment of image quality and consolidation was performed by 3 observers and a semi-automated quantification algorithm was applied to quantify aerated pulmonary volume as an inverse surrogate marker for pulmonary fibrosis. RESULTS: We found a significant correlation between classical Ashcroft scoring and micro-CT assessment using both visual assessment and the semi-automated quantification algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image quality values were higher for respiratory gated exams, although differences were not significant. For assessment of fibrosis no significant difference between respiratory gated and ungated exams was observed. CONCLUSIONS: Together, we show that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both visual assessment and semi-automated quantification algorithms. These data may be important in view of pre-clinical pharmacologic interventions for the treatment of lung fibrosis in small laboratory animals.


Assuntos
Adenoviridae/genética , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/veterinária , Tomografia Computadorizada por Raios X/veterinária , Transfecção/métodos , Fator de Crescimento Transformador beta/genética , Animais , Feminino , Pulmão/diagnóstico por imagem , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/genética , Sensibilidade e Especificidade
20.
Surg Radiol Anat ; 32(8): 791-5, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20623122

RESUMO

PURPOSE: Preclinical and clinical topics are often separated in medical education. For example, surgery and radiology are often taught much later than anatomy. The aim of this study was to establish and to evaluate an interdisciplinary course combining these closely related subjects to enhance medical comprehension. METHODS: Two tutorials each lasting one term were offered to second year medical students, in which clinical topics were implemented linking anatomy to surgical and radiological knowledge. A questionnaire was used to evaluate the success of this approach. RESULTS: The motivation of the students was above average and the practical work was done accurately. The students confirmed that the course improved anatomical comprehension (>95%) and that the learned matters were relevant for their future (90%). Furthermore, interest in the subjects was higher after the course (>85%). Critical suggestions were to extend the course and to include more topics. CONCLUSIONS: A mix of surgery, radiology and anatomy is a teaching concept, which leads to high acceptance and interest in medical students.


Assuntos
Anatomia/educação , Cirurgia Geral/educação , Radiologia/educação , Compreensão , Humanos , Motivação
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