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1.
Eur Radiol ; 31(3): 1443-1450, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32885295

RESUMO

OBJECTIVES: The aim of this retrospective study was to determine cost-effectiveness of stress myocardial CT perfusion (CTP), coronary CT angiography (CTA), and the combination of both in suspected obstructive coronary artery disease (CAD) or in-stent restenosis (ISR) in patients with previous coronary stent implantation. METHODS: A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALYs) associated with CTA, CTP, and CTA + CTP. Model input parameters were obtained from published literature. Probabilistic sensitivity analysis was performed to evaluate overall model uncertainty. A single-variable deterministic sensitivity analysis evaluated the sensitivity of the results to plausible variations in model inputs. Cost-effectiveness was assessed based on a cost-effectiveness threshold of $100,000 per QALY. RESULTS: In the base-case scenario with willingness to pay of $100,000 per QALY, CTA resulted in total costs of $47,013.87 and an expected effectiveness of 6.84 QALYs, whereas CTP resulted in total costs of $46,758.83 with 6.93 QALYs. CTA + CTP reached costs of $47,455.63 with 6.85 QALYs. Therefore, strategies CTA and CTA + CTP were dominated by CTP in the base-case scenario. Deterministic sensitivity analysis demonstrated robustness of the model to variations of diagnostic efficacy parameters and costs in a broad range. CTP was cost-effective in the majority of iterations in the probabilistic sensitivity analysis as compared with CTA. CONCLUSIONS: CTP is cost-effective for the detection of obstructive CAD or ISR in patients with previous stenting and therefore should be considered a feasible approach in daily clinical practice. KEY POINTS: • CTP provides added diagnostic value in patients with previous coronary stents. • CTP is a cost-effective method for the detection of obstructive CAD or ISR in patients with previous stenting.


Assuntos
Doença da Artéria Coronariana , Reestenose Coronária , Imagem de Perfusão do Miocárdio , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/diagnóstico por imagem , Análise Custo-Benefício , Humanos , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos Retrospectivos , Stents , Tomografia Computadorizada por Raios X
2.
Eur Radiol ; 29(11): 6038-6048, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31028444

RESUMO

OBJECTIVES: Globalization and migration are increasing the demand for reports in different languages. We aimed to examine if structured reports created by non-German-speaking radiologists with multilingual templates show significant differences in quality to structured reports and free-text reports by German native speakers. METHODS: We used structured templates that allow radiologists to report in their mother tongue and then switch the report language to German or English automatically using proprietary software. German- and English-speaking radiology residents created structured reports in both German and English with these templates. Reports for three different exam types were created (intensive care chest x-ray, shoulder x-ray specifically for degenerative processes, and CT pulmonary angiogram for pulmonary embolism). The report quality of automatically translated German structured reports by English-speaking radiologists and German structured reports by German radiologists was then evaluated by German clinicians with a standardized questionnaire. The questionnaire was designed to assess attributes including content, comprehensibility, clinical consequences, and overall quality. RESULTS: Structured reports by English-speaking radiologists that were automatically translated into German and German structured reports by German radiologists both received very high or high overall quality ratings in the majority of cases, showing no significant differences in quality. Likewise, no significant differences were observed between the two report types regarding comprehensibility and clinical consequences. Structured reports by German radiologists received significantly better ratings for overall quality and comprehensibility compared to free-text reports by German radiologists. CONCLUSIONS: Multilingual structured reporting templates may serve as a feasible tool for creating high-quality radiology reports in foreign languages. KEY POINTS: • Multilingualism in structured reporting templates can be a useful tool for creating high-quality radiology reports in foreign languages. • German reports created with multilingual structured reporting templates by English-speaking radiologists and German structured reports by German radiologists exhibit no significant differences in overall report quality. • Multilingual structured reporting templates can help radiologists overcome communication barriers and facilitate teleradiology.


Assuntos
Idioma , Multilinguismo , Sistemas de Informação em Radiologia/estatística & dados numéricos , Radiologia/estatística & dados numéricos , Relatório de Pesquisa/normas , Humanos , Reprodutibilidade dos Testes
3.
Am J Transplant ; 18(5): 1275-1277, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29314647

RESUMO

Scarcity of donors leads transplant surgeons to consider extended-criteria lungs and occasionally to accept the unlikely. Here we report a case of successful single lung transplantation from a donor 8 months after double lung transplantation.


Assuntos
Morte Encefálica , Pneumopatias/cirurgia , Transplante de Pulmão/métodos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Transplantados , Resultado do Tratamento
4.
Am J Transplant ; 17(6): 1637-1648, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27931084

RESUMO

Regulatory T cells (Treg) can regulate alloantigens and may counteract chronic lung allograft dysfunction (CLAD) in lung transplantation. We analyzed Treg in peripheral blood prospectively and correlated percentages of subpopulations with the incidence of CLAD at 2 years. Among lung-transplanted patients between January 2009 and July 2011, only patients with sufficient Treg measurements were included into the study. Tregs were measured immediately before lung transplantation, at 3 weeks and 3, 6, 12, and 24 months after transplantation and were defined as CD4+ CD25high T cells and further analyzed for CTLA4, CD127, FoxP3, and IL-2 expressions. Between January 2009 and July 2011, 264 patients were transplanted at our institution. Among the 138 (52%) patients included into the study, 31 (22%) developed CLAD within 2 years after transplantation. As soon as 3 weeks after lung transplantation, a statistically significant positive association was detected between Treg frequencies and later absence of CLAD. At the multivariate analysis, increasing frequencies of CD4+ CD25high CD127low , CD4+ CD25high FoxP3+ and CD4+ CD25high IL-2+ T cells at 3 weeks after lung transplantation emerged as protective factors against development of CLAD at 2 years. In conclusion, higher frequencies of specific Treg subpopulations early after lung transplantation are protective against CLAD development.


Assuntos
Biomarcadores/metabolismo , Linfócitos T CD4-Positivos/imunologia , Pneumopatias/cirurgia , Transplante de Pulmão/métodos , Disfunção Primária do Enxerto/prevenção & controle , Aloenxertos , Antígenos CD4/metabolismo , Doença Crônica , Feminino , Seguimentos , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imunofenotipagem , Interleucina-2/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Subunidade alfa de Receptor de Interleucina-7/metabolismo , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/imunologia , Disfunção Primária do Enxerto/metabolismo , Prognóstico , Estudos Prospectivos , Fatores de Tempo
5.
Eur Radiol ; 27(6): 2532-2537, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27678131

RESUMO

OBJECTIVES: To evaluate the potential role of dual energy CT (DECT) to visualize antiangiogenic treatment effects in patients with metastatic renal cell cancer (mRCC) while treated with tyrosine-kinase inhibitors (TKI). METHODS: 26 patients with mRCC underwent baseline and follow-up single-phase abdominal contrast enhanced DECT scans. Scans were performed immediately before and 10 weeks after start of treatment with TKI. Virtual non-enhanced (VNE) and colour coded iodine images were generated. 44 metastases were measured at the two time points. Hounsfield unit (HU) values for VNE and iodine density (ID) as well as iodine content (IC) in mg/ml of tissue were derived. These values were compared to the venous phase DECT density (CTD) of the lesions. Values before and after treatment were compared using a paired Student's t test. RESULTS: Between baseline and follow up, mean CTD and DECT-derived ID both showed a significant reduction (p < 0.005). The relative reduction measured in percent was significantly greater for ID than for CTD (49.8 ± 36,3 % vs. 29.5 ± 20.8 %, p < 0.005). IC was also significantly reduced under antiangiogenic treatment (p < 0.0001). CONCLUSIONS: Dual energy CT-based quantification of iodine content of mRCC metastases allows for significantly more sensitive and reproducible detection of antiangiogenic treatment effects. KEY POINTS: • A sign of tumour response to antiangiogenic treatment is reduced tumour perfusion. • DECT allows visualizing iodine uptake, which serves as a marker for vascularization. • More sensitive detection of antiangiogenic treatment effects in mRCC is possible.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Pirróis/uso terapêutico , Idoso , Carcinoma de Células Renais/diagnóstico por imagem , Meios de Contraste/metabolismo , Feminino , Humanos , Iodo/metabolismo , Neoplasias Renais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Proteínas Tirosina Quinases/antagonistas & inibidores , Sunitinibe , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
6.
Eur Radiol ; 27(1): 113-119, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27059858

RESUMO

OBJECTIVES: Our aim was to provide further evidence for the efficacy/safety of radioembolization using yttrium-90-resin microspheres for unresectable chemorefractory liver metastases from colorectal cancer (mCRC). METHODS: We followed 104 consecutively treated patients until death. Overall survival (OS) was calculated from the day of the first radioembolization procedure. Response was defined by changes in tumour volume as defined by Response Evaluation Criteria in Solid Tumours (RECIST) v1.0 and/or a ≥30 % reduction in serum carcinoembryonic antigen (CEA) at 3 months. RESULTS: Survival varied between 23 months in patients who had a complete response to prior chemotherapy and 13 months in patients with a partial response or stable disease. Median OS also significantly improved (from 5.8 months to 17.1 months) if response durability to radioembolization extended beyond 6 months. Patients with a positive trend in CEA serum levels (≥30 % reduction) at 3 months post-radioembolization also had a survival advantage compared with those who did not: 15.0 vs 6.7 months. Radioembolization was well tolerated. Grade 3 increases in bilirubin were reported in 5.0 % of patients at 3 months postprocedure. CONCLUSIONS: After multiple chemotherapies, many patients still have a good performance status and are eligible for radioembolization. This single procedure can achieve meaningful survivals and is generally well tolerated. KEY POINTS: • After multiple chemotherapies, many patients are still eligible for radioembolization (RE). • RE can achieve meaningful survival in patients with chemorefractory liver-predominant metastatic colorectal cancer (mCRC). • Tumour responsiveness to prior systemic treatments is a significant determinant of overall survival (OS) after RE. • Radioembolization in patients with a good performance status is generally well tolerated.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Embolização Terapêutica/métodos , Neoplasias Hepáticas/secundário , Radioisótopos de Ítrio/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/métodos , Neoplasias Colorretais/terapia , Feminino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Microesferas , Pessoa de Meia-Idade , Resultado do Tratamento
7.
Am J Transplant ; 16(11): 3150-3162, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27273729

RESUMO

Experimentally, regulatory T cells inhibit rejection. In clinical transplantations, however, it is not known whether T cell regulation is the cause for, or an epiphenomenon of, long-term allograft survival. Here, we study naïve and alloantigen-primed T cell responses of clinical lung transplant recipients in humanized mice. The pericardiophrenic artery procured from human lung grafts was implanted into the aorta of NODrag-/- /IL-2rγc-/- mice reconstituted with peripheral blood mononuclear cells (PBMCs) from the respective lung recipient. Naïve or primed allogeneic PBMCs procured 21 days post-lung transplantation with or without enriching for CD4+ CD25high T cells were used. Transplant arteriosclerosis was assessed 28 days later by histology. Mice reconstituted with alloantigen-primed PBMCs showed significantly more severe transplant arteriosclerosis than did mice with naïve PBMCs (p = 0.005). Transplant arteriosclerosis was equally suppressed by enriching for autologous naïve (p = 0.012) or alloantigen-primed regulatory T cells (Tregs) (p = 0.009). Alloantigen priming in clinical lung recipients can be adoptively transferred into a humanized mouse model. Transplant arteriosclerosis elicited by naïve or alloantigen-primed PBMCs can be similarly controlled by potent autologous Tregs. Cellular therapy with expanded autologous Tregs in lung transplantation might be a promising future strategy.


Assuntos
Arteriosclerose/etiologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/imunologia , Isoantígenos/imunologia , Pneumopatias/imunologia , Transplante de Pulmão/efeitos adversos , Linfócitos T Reguladores/imunologia , Animais , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Pneumopatias/cirurgia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Pessoa de Meia-Idade , Fenótipo , Transplantados , Transplante Homólogo
8.
Am J Transplant ; 16(5): 1579-87, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26607844

RESUMO

This single-center study examines the incidence, etiology, and outcomes associated with prolonged mechanical ventilation (PMV), defined as time to definite spontaneous ventilation >21 days after double lung transplantation (LTx). A total of 690 LTx recipients between January 2005 and December 2012 were analyzed. PMV was necessary in 95 (13.8%) patients with decreasing incidence during the observation period (p < 0.001). Independent predictors of PMV were renal replacement therapy (odds ratio [OR] 11.13 [95% CI, 5.82-21.29], p < 0.001), anastomotic dehiscence (OR 8.74 [95% CI 2.42-31.58], p = 0.001), autoimmune comorbidity (OR 5.52 [95% CI 1.86-16.41], p = 0.002), and postoperative neurologic complications (OR 5.03 [95% CI 1.98-12.81], p = 0.001), among others. Overall 1-year survival was 86.0% (90.4% for LTx between 2010 and 2012); it was 60.7% after PMV and 90.0% in controls (p < 0.001). Conditional long-term outcome among hospital survivors, however, did not differ between the groups (p = 0.78). Multivariate analysis identified renal replacement therapy (hazard ratio [HR] 3.55 [95% CI 2.40-5.25], p < 0.001), post-LTx extracorporeal membrane oxygenation (HR 3.47 [95% CI 2.06-5.83], p < 0.001), and prolonged inotropic support (HR 1.95 [95% CI 1.39-2.75], p < 0.001), among others, as independent predictors of mortality. In conclusion, PMV complicated 14% of LTx procedures and, although associated with increased in-hospital mortality, outcomes among patients surviving to hospital discharge were unaffected.


Assuntos
Oxigenação por Membrana Extracorpórea/mortalidade , Pneumopatias/mortalidade , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Respiração Artificial/mortalidade , Adolescente , Adulto , Criança , Feminino , Seguimentos , Alemanha/epidemiologia , Mortalidade Hospitalar/tendências , Humanos , Incidência , Pneumopatias/complicações , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
9.
Am J Transplant ; 16(5): 1371-82, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26602894

RESUMO

Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4(+) CD25(high+) T cell frequencies were detected in peripheral blood associated with decreased interferon-γ production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with third-party splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donor-specific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells.


Assuntos
Quimerismo , Sobrevivência de Enxerto/imunologia , Isoantígenos/imunologia , Transplante de Pulmão , Linfócitos T Reguladores/efeitos da radiação , Animais , Feminino , Terapia de Imunossupressão , Masculino , Modelos Animais , Suínos , Porco Miniatura , Linfócitos T Reguladores/imunologia , Doadores de Tecidos , Tolerância ao Transplante , Transplante Homólogo , Irradiação Corporal Total
10.
Neuroimage ; 107: 76-84, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25482266

RESUMO

Cognitive conflict control in flanker tasks has often been described using the zoom-lens metaphor of selective attention. However, whether and how selective attention - in terms of suppression and enhancement - operates in this context has remained unclear. To examine the dynamic interplay of selective attention and cognitive control we used electrophysiological measures and presented task-irrelevant visual probe stimuli at foveal, parafoveal, and peripheral display positions. Target-flanker congruency varied either randomly from trial to trial (mixed-block) or block-wise (fixed-block) in order to induce reactive versus proactive control modes, respectively. Three EEG measures were used to capture ad-hoc adjustments within trials as well as effects of context-based predictions: the N1 component of the visual evoked potential (VEP) to probes, the VEP to targets, and the conflict-related midfrontal N2 component. Results from probe-VEPs indicate that enhanced processing of the foveal target rather than suppression of the peripheral flankers supports interference control. In incongruent mixed-block trials VEPs were larger to probes near the targets. In the fixed-blocks probe-VEPs were not modulated, but contrary to the mixed-block the preceding target-related VEP was affected by congruency. Results of the control-related N2 reveal largest amplitudes in the unpredictable context, which did not differentiate for stimulus and response incongruency. In contrast, in the predictable context, N2 amplitudes were reduced overall and differentiated between stimulus and response incongruency. Taken together these results imply that predictability alters interference control by a reconfiguration of stimulus processing. During unpredictable sequences participants adjust their attentional focus dynamically on a trial-by-trial basis as reflected in congruency-dependent probe-VEP-modulation. This reactive control mode also elicits larger N2 amplitudes. In contrast, when task demands are predictable, participants focus selective attention earlier as reflected in the target-related VEPs. This proactive control mode leads to smaller N2 amplitudes and absent probe effects.


Assuntos
Atenção/fisiologia , Conflito Psicológico , Potenciais Evocados Visuais/fisiologia , Adolescente , Adulto , Antecipação Psicológica , Eletroencefalografia , Feminino , Humanos , Masculino , Estimulação Luminosa , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Leitura , Adulto Jovem
11.
Pharmacogenomics J ; 13(3): 286-96, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22614244

RESUMO

Long-term changes in brain gene expression have been identified in alcohol dependence, but underlying mechanisms remain unknown. Here, we examined the potential role of microRNAs (miRNAs) for persistent gene expression changes in the rat medial prefrontal cortex (mPFC) after a history of alcohol dependence. Two-bottle free-choice alcohol consumption increased following 7-week exposure to intermittent alcohol intoxication. A bioinformatic approach using microarray analysis, quantitative PCR (qPCR), bioinformatic analysis and microRNA-messenger RNA (mRNA) integrative analysis identified expression patterns indicative of a disruption in synaptic processes and neuroplasticity. About 41 rat miRNAs and 165 mRNAs in the mPFC were significantly altered after chronic alcohol exposure. A subset of the miRNAs and mRNAs was confirmed by qPCR. Gene ontology categories of differential expression pointed to functional processes commonly associated with neurotransmission, neuroadaptation and synaptic plasticity. microRNA-mRNA expression pairing identified 33 miRNAs putatively targeting 89 mRNAs suggesting transcriptional networks involved in axonal guidance and neurotransmitter signaling. Our results demonstrate a significant shift in microRNA expression patterns in the mPFC following a history of dependence. Owing to their global regulation of multiple downstream target transcripts, miRNAs may have a pivotal role in the reorganization of synaptic connections and long-term neuroadaptations in alcohol dependence. MicroRNA-mediated alterations of transcriptional networks may be involved in disrupted prefrontal control over alcohol drinking observed in alcoholic patients.


Assuntos
Alcoolismo/genética , Regulação da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Córtex Pré-Frontal/metabolismo , RNA Mensageiro/genética , Alcoolismo/patologia , Animais , Etanol/administração & dosagem , Etanol/toxicidade , Masculino , MicroRNAs/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Transdução de Sinais/genética
12.
Radiologe ; 53(6): 495-502, 2013 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-23737010

RESUMO

Computed tomography angiography (CTA) of the aorta is an accepted standard diagnostic procedure for preoperative evaluation and planning of endovascular treatment of abdominal aortic aneurysms (endovascular aortic repair EVAR). The CTA method delivers all relevant anatomical and morphological information on the underlying pathology of the aorta and pelvic axes. Various software solutions are available for multiplanar reconstruction of the CT data for exact measurement of the access routes and landing zones and are essential components of individualized operation planning. The synthesis of all CT-based information allows a safe and exactly targeted release of the stent graft in the aorta. Furthermore, the periprocedural radiation dose can be reduced by a precise preoperative planning of the positions to be irradiated during implantation.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/métodos , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Angiografia/métodos , Humanos , Cuidados Pré-Operatórios/métodos
13.
Mol Psychiatry ; 16(8): 809-17, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20479755

RESUMO

Excessive alcohol use, a major cause of morbidity and mortality, is less well understood than other addictive disorders. Dopamine release in ventral striatum is a common element of drug reward, but alcohol has an unusually complex pharmacology, and humans vary greatly in their alcohol responses. This variation is related to genetic susceptibility for alcoholism, which contributes more than half of alcoholism risk. Here, we report that a functional OPRM1 A118G polymorphism is a major determinant of striatal dopamine responses to alcohol. Social drinkers recruited based on OPRM1 genotype were challenged in separate sessions with alcohol and placebo under pharmacokinetically controlled conditions, and examined for striatal dopamine release using positron emission tomography and [(11)C]-raclopride displacement. A striatal dopamine response to alcohol was restricted to carriers of the minor 118G allele. To directly establish the causal role of OPRM1 A118G variation, we generated two humanized mouse lines, carrying the respective human sequence variant. Brain microdialysis showed a fourfold greater peak dopamine response to an alcohol challenge in h/mOPRM1-118GG than in h/mOPRM1-118AA mice. OPRM1 A118G variation is a genetic determinant of dopamine responses to alcohol, a mechanism by which it likely modulates alcohol reward.


Assuntos
Alcoolismo/genética , Corpo Estriado/metabolismo , Dopamina/metabolismo , Etanol/farmacologia , Predisposição Genética para Doença/genética , Receptores Opioides mu/genética , Receptores Opioides mu/fisiologia , Adulto , Alelos , Animais , Corpo Estriado/fisiologia , Dopamina/fisiologia , Variação Genética , Genótipo , Heterozigoto , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Racloprida
14.
Radiologe ; 51(6): 475-82, 2011 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-21607763

RESUMO

With the introduction of second generation ultrasound contrast agents, contrast-enhanced ultrasound (CEUS) has become available as an adjunct to the conventional FAST (focused assessment with sonography in trauma) protocol and B-mode sonography of the abdomen after blunt force abdominal trauma. Results from several controlled studies indicate excellent diagnostic accuracy of CEUS for the exclusion of clinically relevant parenchymal injuries after blunt force abdominal trauma. Particularly in younger, hemodynamically stable patients this technique could contribute to a reliable exclusion of parenchymal injuries without the use of ionizing radiation. This report provides details on the technical performance of CEUS, shows examples of typical CEUS findings after blunt abdominal trauma and summarizes the current clinical evidence regarding the use of CEUS after blunt abdominal trauma.


Assuntos
Traumatismos Abdominais/diagnóstico por imagem , Meios de Contraste , Aumento da Imagem/métodos , Ultrassonografia/métodos , Ferimentos não Penetrantes/diagnóstico por imagem , Humanos
15.
Neuropsychologia ; 143: 107478, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32360476

RESUMO

Eye contact is a salient social cue, which is assumed to influence already early neural correlates of face perception. Specifically, the N170 component of the event-related potential (ERP) has often been found to be larger for faces with an averted gaze as compared to faces that directly look at the observer. In most existing ERP studies, effects of eye contact were investigated under comparatively artificial conditions where participants were instructed to maintain a steady fixation while they passively observed gaze changes in the stimulus face. It is therefore unclear to what extent neural correlates of eye contact generalize to more naturalistic situations that involve a continuous interplay between directed and averted gaze between the communication partners. To start bridging this gap, the present study compared the passive viewing of gaze changes to an active condition in which the participant's own gaze (measured online with an eye tracker) interacted with the gaze position of a continuously presented stimulus face. We also investigated whether eye contact effects were modulated by the face's emotional expression. In both the passive and the active viewing condition, N170 amplitudes were larger when the gaze of the stimulus faces was averted rather than directed towards the participant. Furthermore, eye contact decreased P300 amplitudes in both conditions. The emotional expression of the face also modulated the N170, but this effect did not interact with that of gaze direction. We conclude that the neural correlates of gaze perception during active gaze interactions are comparable to those found during passive viewing, encouraging the further study of eye contact effects in more naturalistic settings.


Assuntos
Tecnologia de Rastreamento Ocular , Reconhecimento Facial , Encéfalo , Potenciais Evocados , Fixação Ocular , Humanos
16.
Psychopharmacology (Berl) ; 237(6): 1691-1707, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32285159

RESUMO

RATIONALE: Compared to the general population, adult Attention-Deficit / Hyperactivity Disorder (ADHD) is more prevalent in patients with Alcohol Use Disorder (AUD). Impaired behavioral inhibition is a common characteristic in both ADHD and AUD. Relapse risk is increased in patients with AUD and comorbid, untreated ADHD and in AUD patients with increased neural cue-reactivity. OBJECTIVES: In this study, we examined the interaction between neural correlates of behavioral inhibition and alcohol cue-reactivity with a hybrid imaging task. METHODS: Out of 69 adult study participants, we included n = 49 in our final analyses: Individuals had a diagnosis of either AUD (n = 13), ADHD (n = 14) or both (n = 5), or were healthy controls (HC; n = 17). The functional magnetic resonance imaging paradigm aimed to examine the combined effects of both an interference-inhibition task ("Simon-task") and an alcohol cue-reactivity task. Instead of segregating by diagnostic group, we pursued a dimensional approach in which we compared measures of AUD and ADHD severity, as well as the interaction of both, using multiple regression analyses. RESULTS: The four groups did not differ on the behavioral level on either the inhibition task or the alcohol cue-reactivity task. However, brain activation in frontal control and reward-related regions during completion of the combined tasks were related to ADHD and AUD severity (symptom load). During presentation of both alcohol cues and the inhibition task, participants with higher AUD and ADHD symptom load exhibited greater BOLD (blood oxygen level dependent) responses in subcortical reward-related regions. CONCLUSIONS: Our findings support the hypothesis that ADHD additionally diminishes inhibition ability in individuals with AUD. This may increase relapse risk when confronted with alcohol cues. Further, it is crucial for patients with comorbid AUD and ADHD to take into account not only reduced cognitive control over behavioral inhibition but also simultaneously heightened alcohol cue-reactivity.


Assuntos
Alcoolismo/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Sinais (Psicologia) , Inibição Psicológica , Rede Nervosa/diagnóstico por imagem , Adulto , Alcoolismo/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Condicionamento Psicológico/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/métodos , Recompensa , Adulto Jovem
17.
FASEB J ; 22(7): 2552-60, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18367649

RESUMO

Beta-arrestin 2 is a multifunctional key component of the G protein-coupled receptor complex and is involved in mu-opiate and dopamine D2 receptor signaling, both of which are thought to mediate the rewarding effects of ethanol consumption. We identified elevated expression of the beta-arrestin 2 gene (Arrb2) in the striatum and the hippocampus of ethanol-preferring AA rats compared to their nonpreferring counterpart ANA line. Differential mRNA expression was accompanied by different levels of Arrb2 protein. The elevated expression was associated with a 7-marker haplotype in complete linkage disequilibrium, which segregated fully between the lines, and was unique to the preferring line. Furthermore, a single, distinct, and highly significant quantitative trait locus for Arrb2 expression in hippocampus and striatum was identified at the locus of this gene, providing evidence that genetic variation may affect a cis-regulatory mechanism for expression and regional control of Arrb2. These findings were functionally validated using mice lacking Arrb2, which displayed both reduced voluntary ethanol consumption and ethanol-induced psychomotor stimulation. Our results demonstrate that beta-arrestin 2 modulates acute responses to ethanol and is an important mediator of ethanol reward.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/fisiopatologia , Arrestinas/deficiência , Arrestinas/genética , Recompensa , Animais , Comportamento Apetitivo/fisiologia , Regulação da Expressão Gênica , Hibridização In Situ , Camundongos , Camundongos Knockout , RNA Mensageiro/genética , Ratos , beta-Arrestina 2 , beta-Arrestinas
18.
Pharmacopsychiatry ; 42 Suppl 1: S118-28, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19434550

RESUMO

Lists of differentially expressed genes in a disease have become increasingly more comprehensive with improvements on all technical levels. Despite statistical cutoffs of 99% or 95% confidence intervals, the number of genes can rise to several hundreds or even thousands, which is barely amenable to a researcher's understanding. This report describes some ways of processing those data by mathematical algorithms. Gene lists obtained from 53 microarrays (two brain regions (amygdala and caudate putamen), three rat strains drinking alcohol or being abstinent) have been used. They resulted from analyses on Affymetrix chips and encompassed approximately 6 000 genes that passed our quality filters. They have been subjected to four mathematical ways of processing: (a) basic statistics, (b) principal component analysis, (c) hierarchical clustering, and (d) introduction into Bayesian networks. It turns out, by using the p-values or the log-ratios, that they best subdivide into brain areas, followed by a fairly good discrimination into the rat strains and the least good discrimination into alcohol-drinking vs. abstinent. Nevertheless, despite the fact that the relation to alcohol-drinking was the weakest signal, attempts have been made to integrate the genes related to alcohol-drinking into Bayesian networks to learn more about their inter-relationships. The study shows, that the tools employed here are extremely useful for (a) quality control of datasets, (b) for constructing interactive (molecular) networks, but (c) have limitations in integration of larger numbers into the networks. The study also shows that it is often pivotal to balance out the number of experimental conditions with the number of animals.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Tonsila do Cerebelo/metabolismo , Teorema de Bayes , Corpo Estriado/metabolismo , Redes e Vias Metabólicas , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Mensageiro/metabolismo , Animais , Etanol/administração & dosagem , Expressão Gênica/efeitos dos fármacos , Masculino , Modelos Genéticos , Ratos , Ratos Endogâmicos
19.
Clin Hemorheol Microcirc ; 41(3): 151-68, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19276513

RESUMO

Endoleaks following endovascular aneurysm repair (EVAR) are common and present a diagnostic challenge in the follow-up after EVAR. Contrast-enhanced ultrasound (CEUS) with low mechanical index (low MI) is a promising new method for the diagnosis and follow-up of endoleaks. CEUS with SonoVue allows a more rapid and noninvasive diagnosis, especially in critical patients owing to its bedside availability. This review describes the etiology, classification and importance of different types of endoleaks and compares CEUS findings with computed tomography angiography (CTA), allowing the reader to appreciate the usefulness of CEUS in this clinical situation.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Hemorragia/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Angiografia/métodos , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/cirurgia , Meios de Contraste , Hemorragia/etiologia , Humanos , Ultrassonografia/métodos
20.
Radiologe ; 49(3): 242-5, 248-51, 2009 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-19198795

RESUMO

PURPOSE: To determine the value of MR enteroclysis (MRE) in the localization and characterization of primary carcinoid tumors of the small bowel and to describe typical imaging features. MATERIAL AND METHODS: Twenty patients with suspicion of primary small bowel carcinoid tumors (pCT) were recruited to undergo MRE following nasojejunal intubation and small bowel filling with 2.5 l of 0.5% methylcellulose solution under MR fluoroscopic guidance. MRE was performed on a 1.5 T MR scanner including T2w SSFSE, SSFP and contrast enhanced T1w GRE sequences with fat saturation. Fifteen patients, who subsequently had surgery for resection of their pCT, were retrospectively included in the study. All MRE were analyzed as for the presence, location, number, size, multiplicity and morphologic appearance of the pCT by two board certified radiologists in consensus. The conspicuity of the tumors was rated for each sequence type separately, according to a 4-point rating scale. Signal intensity measurements were performed in tumor and muscle. The presence of desmoplastic reaction, vascular involvement and lymph node metastases was also analyzed. RESULTS: pCT were correctly identified and localized in 14/15 patients. Due to their hyperenhancement tumors was best detected on contrast-enhanced T1w fat saturated GRE sequences. SSFSE was clearly inferior with the tumors being either hyperintense or isointense to muscle. pCT appeared as nodular intraluminal masses in 40% of the cases, as focal wall thickening in 33.3% and in 20% with both. Mean size was 25 (7-46 mm) with a tendency to smaller size for ileal tumors. MRE failed to depict superficial micronodular peritoneal spread in one patient. Desmoplastic reaction was observed in 73.3% of the cases with mesenteric masses exhibiting lower signal than the pCT due to fibrotic changes. CONCLUSION: MRE is a valuable method for the detection and localization of primary carcinoid tumors, provided that appropriate bowel distension is achieved. Various characteristic morphologic features could be identified which may contribute to characterize pCT and their loco-regional metastases.


Assuntos
Tumor Carcinoide/diagnóstico , Meios de Contraste/administração & dosagem , Processamento de Imagem Assistida por Computador , Neoplasias Intestinais/diagnóstico , Intestino Delgado , Imageamento por Ressonância Magnética , Metilcelulose/administração & dosagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/patologia , Tumor Carcinoide/cirurgia , Progressão da Doença , Feminino , Fluoroscopia , Gadolínio DTPA , Humanos , Neoplasias do Íleo/diagnóstico , Neoplasias do Íleo/patologia , Neoplasias do Íleo/cirurgia , Neoplasias Intestinais/patologia , Neoplasias Intestinais/cirurgia , Intestino Delgado/patologia , Intestino Delgado/cirurgia , Intubação Gastrointestinal , Neoplasias do Jejuno/diagnóstico , Neoplasias do Jejuno/patologia , Neoplasias do Jejuno/cirurgia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Prognóstico , Estudos Retrospectivos
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