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1.
BMC Health Serv Res ; 22(1): 44, 2022 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-34998395

RESUMO

BACKGROUND: Clinical quality registries (CQRs) can likely improve quality in healthcare and research. However, studies indicate that effective use of CQRs is hindered by lack of engagement and interest among stakeholders, as well as factors related to organisational context, registry design and data quality. To fulfil the potential of CQRs, more knowledge on stakeholders' perceptions of the factors that will facilitate or hamper the development of CQRs is essential to the more appropriate targeting of registry implementation and the subsequent use of the data. The primary aim of this study was to examine factors that can potentially affect the development of a national CQR for interventional radiology in Norway from the perspective of stakeholders. Furthermore, we wanted to identify the intervention functions likely to enable CQR development. Only one such registry, located in Sweden, has been established. To provide a broader context for the Norwegian study, we also sought to investigate experiences with the development of this registry. METHODS: A qualitative study of ten Norwegian radiologists and radiographers using focus groups was conducted, and an in-depth interview with the initiator of the Swedish registry was carried out. Questions were based on the Capability, Opportunity and Motivation for Behaviour Model and the Theoretical Domains Framework. The participants' responses were categorised into predefined themes using a deductive process of thematic analysis. RESULTS: Knowledge of the rationale used in establishing a CQR, beliefs about the beneficial consequences of a registry for quality improvement and research and an opportunity to learn from a well-developed registry were perceived by the participants as factors facilitating CQR development. The study further identified a range of development barriers related to environmental and resource factors (e.g., a lack of organisational support, time) and individuallevel factors (e.g., role boundaries, resistance to change), as well as several intervention functions likely to be appropriate in targeting these barriers. CONCLUSION: This study provides a deeper understanding of factors that may be involved in the behaviour of stakeholders regarding the development of a CQR. The findings may assist in designing, implementing and evaluating a methodologically rigorous CQR intervention.


Assuntos
Motivação , Radiologia Intervencionista , Atenção à Saúde , Humanos , Pesquisa Qualitativa , Sistema de Registros
2.
PLoS One ; 14(12): e0226479, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31830762

RESUMO

BACKGROUND: The effect of statins over time on coronary atherosclerosis in patients with inflammatory joint diseases (IJD) is unknown. Our aim was to evaluate the change in coronary plaque morphology and volume in long-term statin-treated patients with IJD. METHODS: Sixty-eight patients with IJD and carotid artery plaque(s) underwent coronary computed tomography angiography before and after a mean of 4.7 (range 4.0-6.0) years of statin treatment. The treatment target for low density lipoprotein cholesterol (LDL-c) was ≤1.8 mmol/L. Changes in plaque volume (calcified, mixed/soft and total) and coronary artery calcification (CAC) from baseline to follow-up were assessed using the 17-segment American Heart Association-model. RESULTS: Median (IQR) increase in CAC after statin treatment was 38 (5-236) Agatston units (p<0.001). Calcified and total plaque volume increased with 5.6 (0.0-49.1) and 2.9 (0.0-23.5) mm3, respectively (p<0.001 for both). The median (IQR) change in soft/mixed plaque volume was -10 (-7.1-0.0), p = <0.001. Patients who had obtained the LDL-c treatment target at follow-up, experienced reduced progression of both CAC and total plaque volume compared to patients with LDL-c >1.8mmol/L (21 [2-143] vs. 69 [16-423], p = 0.006 and 0.65 [-1.0-13.9] vs. 13.0 [0.0-60.8] mm3, p = 0.019, respectively). CONCLUSIONS: A progression of total atherosclerotic plaque volume in statin-treated patients with IJD was observed. However, soft/mixed plaque volume was reduced, suggesting an alteration in plaque composition. Patients with recommended LDL-c levels at follow-up had reduced atherosclerotic progression compared to patients with LDL-c levels above the treatment target, suggesting a beneficial effect of treatment to guideline-recommended lipid targets in IJD patients.


Assuntos
Aterosclerose/prevenção & controle , Doença da Artéria Coronariana/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inflamação/tratamento farmacológico , Artropatias/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/patologia , LDL-Colesterol/metabolismo , Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Inflamação/patologia , Artropatias/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
Cardiovasc Diabetol ; 18(1): 58, 2019 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-31054573

RESUMO

OBJECTIVES: The aim was to assess coronary atherosclerosis, plaque morphology and associations to cardiovascular risk factors and epicardial adipose tissue (EAT) in patients with long duration of type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: Eighty-eight patients with ≥ 45 year T1DM duration and 60 controls underwent coronary CT angiography (CCTA) for evaluation of coronary artery plaque volume (total, calcified or mixed/soft), coronary artery calcification score (CAC) and EAT. RESULTS: Plaques were detected in 75 (85%) T1DM patients and 28 (47%) controls, p < 0.01. Median (interquartile range) plaque volume (mm3) in T1DM vs. controls was: 21.0 (1.0-66.0) vs. 0.2 (0.0-7.1), p < 0.01 for calcified, 0.0 (0.0-8.7) vs. 0.0 (0.0-0.0), p < 0.01 for soft/mixed and 29.5 (3.9-95.8) vs. 0.4 (0.0-7.4), p < 0.01 for total plaque volume. Median CAC was 128 (13-671) vs. 1 (0.0-39.0), p < 0.01 in T1DM vs. controls. Median EAT volume did not differ between the groups; 52.3 (36.1-65.5) cm3 vs. 55 (38.3-79.6), p = 0.20. No association between CAC or plaque volumes and EAT were observed. Low time-weighted LDL-cholesterol and HbA1c for 30 years were associated with having plaque volume < 25th percentile, OR (95% CI) 0.18 (0.05-0.70), p = 0.01 and 0.45 (0.20-1.00), p < 0.05, respectively. Time-weighted LDL-c was linearly associated with CAC (beta 0.82 (95% CI 0.03-1.62), p = 0.04) and total plaque volume (beta 0.77 (95% CI 0.19-1.36), p = 0.01). CONCLUSION: Long-term survivors of T1DM have a higher prevalence of coronary atherosclerosis compared to controls. Low LDL-cholesterol and HbA1c over time have a protective effect on coronary atherosclerosis. EAT volume was not associated with coronary atherosclerosis in T1DM patients.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Diabetes Mellitus Tipo 1/epidemiologia , Pericárdio/diagnóstico por imagem , Placa Aterosclerótica , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , LDL-Colesterol/sangue , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Fatores de Risco , Sobreviventes , Fatores de Tempo , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia
4.
J Diabetes Complications ; 33(5): 383-389, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30846232

RESUMO

AIMS: We studied the total prevalence of obstructive coronary artery disease (CAD), undiagnosed CAD and absent CAD in persons with ≥45-year duration of type 1 diabetes (T1D) versus controls, and associations with mean HbA1c, LDL-cholesterol and blood pressure over 2-3 decades. METHODS: We included 76% (n = 103) of all persons with T1D diagnosed ≤1970 attending a diabetes center and 63 controls without diabetes. We collected 20-30 years of HbA1c, LDL-cholesterol and blood pressure measurements. Participants without previously diagnosed coronary heart disease (CHD) underwent Computed Tomography Coronary Angiography (CTCA). Undiagnosed obstructive CAD was defined as any coronary stenosis >50% on CTCA, absent CAD as no detected plaque, and total obstructive CAD as either obstructive CAD on CTCA or previous CHD diagnosis. RESULTS: The prevalence of undiagnosed, absent and obstructive CAD was 24% (21/88), 16% (14/88) and 35% (36/103) in T1D versus 10% (6/60), 50% (30/60) and 14% (9/63) in controls (all p < 0.05). Mean HbA1c was associated with undiagnosed obstructive CAD (OR 2.30 95% C.I. 1.13-4.69), while mean LDL-cholesterol was inversely associated with absent CAD (0.12, 0.04-0.43). CONCLUSIONS: The prevalence of undiagnosed obstructive CAD was high (24%) in this cohort of long-term survivors with T1D. Mean LDL-cholesterol and HbA1c were associated with CAD.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Idoso , Pressão Sanguínea , Estudos de Casos e Controles , LDL-Colesterol/sangue , Estudos Transversais , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Prevalência , Fatores de Risco , Fatores de Tempo
5.
RMD Open ; 3(2): e000544, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28955501

RESUMO

OBJECTIVE: Low association between cardiac symptoms and coronary artery disease (CAD) in patients with inflammatory joint diseases (IJD) demands for objective markers to improve cardiovascular risk stratification. Our main aim was to evaluate the prevalence and characteristics of CAD in patients with IJD with carotid artery plaques. Furthermore, we aimed to assess associations of carotid ultrasonographic findings and coronary plaques. METHODS: Eighty-six patients (61% female) with IJD (55 with rheumatoid arthritis, 21 with ankylosing spondylitis and 10 with psoriatic arthritis) and carotid artery plaque were referred to coronary CT angiography (CCTA). CAD was evaluated using the modified 17-segment American Heart Association model. Calcium score, plaque composition, segment involvement score and segment stenosis score were assessed and correlated to the carotid artery plaques and cardiovascular disease risk factors in logistic and linear regression analyses. Risk prediction models were tested with various cut-off values for associating variables. RESULTS: Fifty-five patients (66%) had CAD assessed by CCTA and 36 (43%) of these had coronary plaques defined as either mixed or soft. Eleven patients (13%) had obstructive CAD. The best risk prediction model (area under the curve: 0.832, 95% CI 0.730 to 0.935) included the combination of variables with cut-off values: age ≥55 years (OR: 12.18, 95% CI 2.80 to 53.05), the carotid-intima media thickness ≥0.7 mm (OR: 4.08, 95% CI 1.20 to 13.89) and carotid plaque height ≥1.5 mm (OR: 8.96, 95% CI 1.68 to 47.91), p<0.05. CONCLUSION: Presence of carotid plaque is alone not sufficient to identify patients at risk for CAD, and a combination of ultrasonographic measurements may be useful in risk stratification of patients with IJD. TRIAL REGISTRATION NUMBER: NCT01389388, Results.

6.
Lancet Haematol ; 3(2): e64-71, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26853645

RESUMO

BACKGROUND: Post-thrombotic syndrome is a common complication after acute proximal deep vein thrombosis (DVT) and is associated with reduced quality of life and a substantial cost burden. In the 2-year results of the CaVenT study, additional catheter-directed thrombolysis reduced the risk of post-thrombotic syndrome by 14% compared with conventional therapy, but did not affect quality of life. In this study we report results at the 5-year follow-up, aiming to assess whether findings for post-thrombotic syndrome and quality of life have persisted. METHODS: Between Jan 3, 2006, and Dec 22, 2009, we recruited patients aged 18-75 years with a first-time high proximal leg DVT from 20 hospitals in the Norwegian southeastern health region. With sealed envelopes, participants were randomly assigned (1:1) to standard treatment with compression stockings and anticoagulants (control group) or to standard treatment plus catheter-directed thrombolysis with alteplase within 21 days from symptom onset. Pre-specified outcomes in this analysis were post-thrombotic syndrome at 5 years as assessed with the Villalta score and scores for quality of life at 5 years with EQ-5D and the disease-specific VEINES-QOL/Sym. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00251771. FINDINGS: At 5 year follow-up (last date Oct 14, 2014), data were available for 176 patients (84% of the 209 patients originally randomised)--87 originally assigned to catheter-directed thrombolysis and 89 originally assigned to the control group. 37 patients (43%; 95% CI 33-53) allocated to catheter-directed thrombolysis developed post-thrombotic syndrome, compared with 63 (71%; 95% CI 61-79) allocated to the control group (p<0·0001), corresponding to an absolute risk reduction of 28% (95% CI 14-42) and a number needed to treat of 4 (95% CI 2-7). Four (5%) patients assigned to catheter-directed thrombolysis and one (1%) to standard treatment had severe post-thrombotic syndrome (Villalta score ≥ 15 or presence of an ulcer). Quality-of-life scores with either assessment scale did not differ between the treatment groups. INTERPRETATION: Additional catheter-directed thrombolysis resulted in a persistent and increased clinical benefit during follow-up for up to 5 years, supporting the use of additional catheter-directed thrombolysis in patients with extensive proximal DVT. However, allocation to this therapy did not lead to better quality of life. The optimal endovascular thrombolytic approach needs further investigation. FUNDING: Southeastern Norway Regional Health Authority, the Research Council of Norway, University of Oslo, Oslo University Hospital.


Assuntos
Síndrome Pós-Trombótica/etiologia , Trombose Venosa/complicações , Adulto , Idoso , Anticoagulantes/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Trombólise Mecânica/efeitos adversos , Pessoa de Meia-Idade , Noruega , Qualidade de Vida , Meias de Compressão , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêutico , Trombose Venosa/terapia
7.
J Vasc Surg Venous Lymphat Disord ; 2(2): 123-30, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26993176

RESUMO

BACKGROUND: Deep vein thrombosis (DVT) often results in venous valvular incompetence and incomplete recanalization, followed by post-thrombotic syndrome (PTS). Treatment with additional catheter-directed thrombolysis (CDT) in patients with an iliofemoral DVT has been shown to reduce the frequency of PTS. The objective of this study was to assess the effect of CDT on venous reflux and patency and to identify possible predictors for the development of PTS. METHODS: Open, multicenter, randomized, controlled clinical trial. Patients (18-75 years) with a first-time iliofemoral DVT were randomized to receive conventional treatment with anticoagulation and compression stockings or CDT in addition to conventional treatment. Follow-up after 6 and 24 months included ultrasound and air plethysmography for evaluation of venous reflux and patency. PTS was assessed with the Villalta score. Possible predictors of PTS were analyzed in multivariate logistic regression models. RESULTS: Following additional CDT, deep venous reflux was detected in 65.2% (95% confidence interval [CI], 54.8-74.2) of patients at 6 months and 66.7% (95% CI, 56.4-75.6) at 24 months. The absolute risk reduction of deep venous reflux was 11.9% (95% CI, 1.1-24.9) after 6 months and 16.5% (95% CI, 4.2-28.8) after 24 months in the CDT arm compared with controls. Correspondingly, venous patency was regained in 65.9% (95% CI, 55.5-75.0) of patients at 6 months and 74.7% (95% CI, 64.9-82.6) after 24 months. Patency was regained in 18.5% (95% CI, 4.4-32.6) more patients after 6 months and 15.1% (95% CI, 1.8-28.5) more patients after 24 months compared with controls. Independent of treatment allocation, patients with fully recanalized and competent deep veins at 6-month follow-up had a 40.5% (95% CI, 26.4-54.7) absolute risk reduction of developing PTS compared with patients with abnormal vein assessment. Reflux and lack of patency at 6 months were found to be independent predictors of PTS development in patients treated with CDT (odds ratio, 8.3; 95% CI, 2.6-26.8 for patients with reflux, and odds ratio, 0.17; 95% CI, 0.06-0.49 for patients with patency). CONCLUSIONS: Additional CDT improved patency and reduced reflux. Both parameters were found to be strong predictors of PTS in patients treated with CDT. Noninvasive vein assessments of patency and reflux may be helpful to identify and monitor patients at high risk of PTS. Our findings provide evidence for the importance of early recanalization with CDT for acute iliofemoral DVT.

8.
BMJ Open ; 3(8): e002984, 2013 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-23988361

RESUMO

OBJECTIVES: To investigate whether additional catheter-directed thrombolysis (CDT) improves long-term quality of life (QOL) compared with standard treatment with anticoagulation and compression stockings alone in patients with proximal deep vein thrombosis (DVT). DESIGN: Open-label randomised controlled trial. SETTING: 19 Hospitals in the Norwegian southeastern health region. PARTICIPANTS: Patients (18-75 years) with a high proximal DVT, symptoms <21 days and no increased risk of bleeding were eligible. 189 of 209 recruited patients completed 24 months of follow-up. INTERVENTIONS: Participants were randomised to additional CDT with alteplase for 1-4 days or to standard treatment only with 6 months of anticoagulation and 24 months of compression stockings. PRIMARY AND SECONDARY OUTCOME MEASURES: Planned secondary outcome measures included QOL as assessed with the generic instrument EQ-5D and the disease-specific instrument VEINES-QOL/Sym. Primary outcome measure was post-thrombotic syndrome (PTS) after 24 months. RESULTS: After 24 months there were no differences in QOL between the additional CDT and standard treatment arms; mean difference for the EQ-5D index was 0.04 (95% CI -0.10 to 0.17), for the VEINES-QOL score 0.2 (95% CI -2.8 to 3.0) and for the VEINES-Sym score 0.5 (95% CI -2.4 to 3.4; p values>0.37). Independent of treatment arms, patients with PTS had poorer outcomes than patient without PTS; mean difference for EQ-5D was 0.09 (95% CI 0.03 to 0.15), for VEINES-QOL score 8.6 (95% CI 5.9 to 11.2) and for VEINES-Sym score 9.8 (95% CI 7.3 to 12.3; p values<0.001). CONCLUSIONS: QOL did not differ between patients treated with additional CDT compared with standard treatment alone. Patients who developed PTS reported poorer QOL and more symptoms than patients without PTS. QOL should be included as an outcome measure in clinical studies on patients at risk of PTS. TRIAL REGISTRATION: NCT00251771.

9.
J Vasc Interv Radiol ; 24(1): 17-24; quiz 26, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23176966

RESUMO

PURPOSE: Catheter-directed thrombolysis (CDT) for proximal deep vein thrombosis (DVT) effectively enhances clot removal and recently has been shown to reduce the development of postthrombotic syndrome (PTS). This study was performed to identify potential markers for early and long-term efficacy of CDT, adverse events, and their interrelationship. MATERIALS AND METHODS: Patients aged 18-75 years (mean, 54 y; 33 women) with first-time proximal DVT and symptoms up to 21 days were included in subanalyses in an open, multicenter, randomized, controlled trial. Early efficacy was assessed with a thrombus score based on daily venography. Six-month and 2-year follow-up included iliofemoral patency assessed with duplex ultrasound and air plethysmography, and PTS was assessed with the Villalta scale. RESULTS: A mean clot resolution of 82%±25 was achieved in 92 patients. Successful lysis (ie,≥50%) was obtained in 83 patients. Early efficacy was equal for femoral and iliofemoral thrombus and not related to thrombus load before CDT, symptom duration, or predisposing risk factors. Lower thrombus score at completion of CDT was associated with increased patency at 24 months (P = .040), and increased patency after 6 and 24 months was correlated with reduced development of PTS after 24 months (P<.001). Bleeding complications were mainly related to the puncture site, and popliteal vein access led to fewer bleeding incidents. CONCLUSIONS: Comp, this is a Clinical Study article, so, as noted on the TOC, the Conclusions section of the abstract gets listed on the TOC. CDT via popliteal access was safe, effectively removed clots, and restored iliofemoral patency. Preprocedure evaluation did not identify patients who did not benefit from treatment. Early efficacy and follow-up patency are of importance to reduce the risk for PTS.


Assuntos
Cateterismo Periférico/estatística & dados numéricos , Terapia Trombolítica/estatística & dados numéricos , Ativador de Plasminogênio Tecidual/administração & dosagem , Trombose Venosa/tratamento farmacológico , Trombose Venosa/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Fatores de Risco , Resultado do Tratamento , Trombose Venosa/diagnóstico , Adulto Jovem
10.
Lancet ; 379(9810): 31-8, 2012 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-22172244

RESUMO

BACKGROUND: Conventional anticoagulant treatment for acute deep vein thrombosis (DVT) effectively prevents thrombus extension and recurrence, but does not dissolve the clot, and many patients develop post-thrombotic syndrome (PTS). We aimed to examine whether additional treatment with catheter-directed thrombolysis (CDT) using alteplase reduced development of PTS. METHODS: Participants in this open-label, randomised controlled trial were recruited from 20 hospitals in the Norwegian southeastern health region. Patients aged 18-75 years with a first-time iliofemoral DVT were included within 21 days from symptom onset. Patients were randomly assigned (1:1) by picking lowest number of sealed envelopes to conventional treatment alone or additional CDT. Randomisation was stratified for involvement of the pelvic veins with blocks of six. We assessed two co-primary outcomes: frequency of PTS as assessed by Villalta score at 24 months, and iliofemoral patency after 6 months. Analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00251771. FINDINGS: 209 patients were randomly assigned to treatment groups (108 control, 101 CDT). At completion of 24 months' follow-up, data for clinical status were available for 189 patients (90%; 99 control, 90 CDT). At 24 months, 37 (41·1%, 95% CI 31·5-51·4) patients allocated additional CDT presented with PTS compared with 55 (55·6%, 95% CI 45·7-65·0) in the control group (p=0·047). The difference in PTS corresponds to an absolute risk reduction of 14·4% (95% CI 0·2-27·9), and the number needed to treat was 7 (95% CI 4-502). Iliofemoral patency after 6 months was reported in 58 patients (65·9%, 95% CI 55·5-75·0) on CDT versus 45 (47·4%, 37·6-57·3) on control (p=0·012). 20 bleeding complications related to CDT included three major and five clinically relevant bleeds. INTERPRETATION: Additional CDT should be considered in patients with a high proximal DVT and low risk of bleeding. FUNDING: South-Eastern Norway Regional Health Authority; Research Council of Norway; University of Oslo; Oslo University Hospital.


Assuntos
Anticoagulantes/uso terapêutico , Cateterismo Periférico , Veia Femoral , Veia Ilíaca , Terapia Trombolítica , Trombose Venosa/tratamento farmacológico , Doença Aguda , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Pós-Trombótica/etiologia , Resultado do Tratamento
11.
Am J Pathol ; 180(2): 457-72, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22142811

RESUMO

Aberrant contact-inhibited proliferation and differentiation induction couple with tumor severity, albeit with an imprecise association with prognosis. Assessment of contact inhibition and differentiation-promoting culture in this study of normal and immortalized oral keratinocytes (NOK and SVpgC2a, respectively) demonstrated elevated cloning ability and saturation density in the immortalized versus normal state, including consistent absence of differentiated morphological features. Transcriptomic analysis implicated 48 gene ontology categories, 8 molecular networks, and 10 key regulator genes in confluency-induced differentiation of NOK, all of which remained nonregulated in SVpgC2a. The SVpgC2a versus NOK transcriptome enriched 52 gene ontology categories altogether, 18 molecular networks, and 39 key regulator genes, several of which were associated with epithelial-mesenchymal transition. Assessment of the previously described gene sets relative to training data sets of head and neck squamous cell carcinoma samples, one including data on tumor differentiation and patient outcome and one present in the Human Gene Expression Map, identified four genes with association to poor survival (COX7A1, MFAP5, MPDU1, and POLD1). This gene set predicted poor outcome in an independent data set of 71 head and neck squamous cell carcinomas. The present study defines, for the first time to our knowledge, the broad gene spectrum that couples to induction, and loss, of oral keratinocyte differentiation. Bioinformatics assessments of the results relative to clinical data generated novel differentiation-related tumor biomarkers relevant to patient outcome.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Transformação Celular Neoplásica/genética , Neoplasias de Cabeça e Pescoço/genética , Queratinócitos/patologia , Apoptose/genética , Carcinoma de Células Escamosas/patologia , Comunicação Celular/genética , Diferenciação Celular/genética , Proteínas Contráteis/genética , DNA Polimerase III/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Proteínas da Matriz Extracelular/genética , Perfilação da Expressão Gênica , Genes Neoplásicos/genética , Genômica/métodos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Análise em Microsséries , Prognóstico , Precursores de Proteínas , Fatores de Processamento de RNA , Células Tumorais Cultivadas
12.
J Magn Reson Imaging ; 31(2): 416-24, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20099355

RESUMO

PURPOSE: To assess image quality, vessel visualization, preliminary diagnostic properties, and interobserver variability of a novel balanced turbo field echo (b-TFE) sequence and contrast-enhanced T1 fast field echo (CE-FFE) sequence with blood pool agent (BPA). MATERIALS AND METHODS: A total of 15 healthy volunteers and six patients with ultrasound-verified proximal deep vein thrombosis (DVT) were examined from the inferior vena cava (IVC) to the proximal calf veins. RESULTS: The great majority of deep veins were completely visualized on both sequences. In healthy volunteers the IVC was completely visualized in five b-TFE and 11 CE-FFE scans, and partially in seven b-TFE and four CE-FFE scans (P = 0.008). Poorest image quality was in the pelvis. Contrast-to-noise ratio (CNR) was higher on b-TFE compared to CE-FFE, with significant difference in calf images (P = 0.036). Sensitivity was 100% for proximal DVT with both methods. Specificity was 70% (CE-FFE) and 80% (b-TFE) for proximal femoral DVT; 100% in distal femoral. Interobserver reliability was kappa 1.0 (b-TFE), 0.9 (CE-FFE) for proximal, and overall poor for distal DVT. CONCLUSION: Contrast-enhancement did not add valuable information in visualizing deep veins of the lower limbs compared to b-TFE, though the IVC was slightly better visualized. Diagnostic properties and interobserver reliability of both sequences were good for proximal DVT and poor for distal DVT.


Assuntos
Algoritmos , Gadolínio , Aumento da Imagem/métodos , Angiografia por Ressonância Magnética/métodos , Compostos Organometálicos , Veias/patologia , Trombose Venosa/patologia , Adulto , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
14.
Eur J Oral Sci ; 111(1): 34-41, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12558806

RESUMO

The current study was undertaken to analyse growth and differentiation-related functions of normal keratinocytes (NOK) and an SV40T-immortalized keratinocyte line (SVpgC2a) from buccal mucosa, viewing the latter cell line as a model of a dysplastic epithelium. Morphological and immunohistochemical assessments of organotypic epithelia generated from 10 or 17 d of culture showed three- to five-fold higher apoptotic and proliferative activity in SVpgC2a relative to NOK. Conditions with or without serum (up to 10%) did not significantly influence these parameters in NOK whereas serum supported proliferation of SVpgC2a. Both cell types showed basal expression of collagen IV and laminin 1, indicating basal lamina, as well as vimentin, indicating an activated, proliferative state. Reduced expression of keratin, including the non-keratinizing marker K13, was seen in SVpgC2a. Assessment of proliferative monolayer cultures by microarray showed that NOK transcribed tissue-specific keratins, but also the epidermal keratin K2a, several simple epithelial keratins and low levels of hair keratins. SVpgC2a transcribed keratins seen in epithelial dysplasia, and K2a and hair keratins, albeit at low level. Overall, the results implied aberrant apoptosis, proliferation and keratin expression in the immortalized state of SVpgC2a. Comparison of NOK and SVpgC2a under identical culture conditions may serve to model the progression from a normal to a pre-neoplastic state of buccal epithelium.


Assuntos
Transformação Celular Neoplásica/metabolismo , Queratinócitos/citologia , Queratinócitos/metabolismo , Queratinas/biossíntese , Mucosa Bucal/citologia , Apoptose , Técnicas de Cultura de Células , Diferenciação Celular , Divisão Celular , Linhagem Celular Transformada/fisiologia , Células Cultivadas , Colágeno Tipo IV/biossíntese , Meios de Cultura Livres de Soro , Humanos , Técnicas Imunoenzimáticas , Laminina/biossíntese , Análise de Sequência com Séries de Oligonucleotídeos , Especificidade de Órgãos , RNA Mensageiro/análise , Vimentina/biossíntese
15.
Altern Lab Anim ; 31(6): 575-85, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15560747

RESUMO

Extracellular matrix proteins affect the growth and survival of epithelial tissues. Accordingly, surface coating with fibronectin and collagen is a common practice for promoting keratinocyte culture. In this study, the expression of fibronectin and collagen-related factors, including integrins, by normal (NOK), SV40 T-antigen-immortalised (SVpgC2a) and malignant (SqCC/Y1) human oral keratinocytes, under standardised, serum-free conditions, was investigated by using microarray analysis. Cell growth was also studied in the presence and absence of a matrix consisting of human fibronectin and bovine collagen type I (FN-COL). Fibronectin transcripts were abundant in all cells, whereas 16 of 29 collagen chains and 14 of 24 integrin subunits were variably detected. With regard to both the expression level and the number of transcripts, higher collagen and lower integrin expression was observed in SVpgC2a cells than in NOKs and SqCC/Y1 cells. The cell types differed with regard to colony-forming efficiency and the rate and kinetics of growth at high cell density. For all cell types, FN-COL coating consistently stimulated cell migration, without influencing growth in mass culture or clonal density. The results demonstrate the transcription of genes associated with the formation and function of fibronectin and collagen in oral epithelium, and variably altered expression patterns in transformed states, and show that keratinocyte lines can be successfully transferred without the stimulus from extracellular FN-COL.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Colágeno/biossíntese , Fibronectinas/biossíntese , Integrinas/biossíntese , Queratinócitos/metabolismo , Neoplasias Bucais/metabolismo , Antígenos Transformantes de Poliomavirus/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Transformada , Linhagem Celular Tumoral , Transformação Celular Viral , Colágeno/genética , Fibronectinas/genética , Perfilação da Expressão Gênica , Humanos , Integrinas/genética , Queratinócitos/patologia , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/metabolismo
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