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1.
ACS Chem Biol ; 19(2): 392-406, 2024 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-38317495

RESUMEN

Heat shock protein 70 (Hsp70) isoforms are key players in the regulation of protein homeostasis and cell death pathways and are therefore attractive targets in cancer research. Developing nucleotide-competitive inhibitors or allosteric modulators, however, has turned out to be very challenging for this protein family, and no Hsp70-directed therapeutics have so far become available. As the field could profit from alternative starting points for inhibitor development, we present the results of a fragment-based screening approach on a two-domain Hsp70 construct using in-solution NMR methods, together with X-ray-crystallographic investigations and mixed-solvent molecular dynamics simulations. The screening protocol resulted in hits on both domains. In particular, fragment binding in a deeply buried pocket at the substrate-binding domain could be detected. The corresponding site is known to be important for communication between the nucleotide-binding and substrate-binding domains of Hsp70 proteins. The main fragment identified at this position also offers an interesting starting point for the development of a dual Hsp70/Hsp90 inhibitor.


Asunto(s)
Proteínas HSP70 de Choque Térmico , Simulación de Dinámica Molecular , Proteínas HSP70 de Choque Térmico/metabolismo , Dominios Proteicos , Espectroscopía de Resonancia Magnética , Nucleótidos/metabolismo , Unión Proteica , Proteínas HSP90 de Choque Térmico/metabolismo
2.
Eur Radiol ; 23(4): 938-42, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23138384

RESUMEN

OBJECTIVE: To compare tumour-to-liver contrast (TLC) of C-arm CT during hepatic arteriography (CACTHA) acquired using three protocols in patients with HCC. METHODS: This prospective study was IRB approved and informed consent was obtained from each patient. Twenty-nine patients (mean age, 68 ± 7 years; 27 men) with 55 HCCs (mean diameter, 2.6 ± 1.5 cm) underwent three different CACTHA protocols in random order before chemoembolisation. Contrast medium (100 mg iodine/ml) was injected into the common hepatic artery (flow rate 4 ml/s). The imaging delay for the start of the CACTHA examination was 4 s (protocol A), 8 s (protocol B) and 12 s (protocol C) (total amount of injected contrast medium: 48 ml, 64 ml, 80 ml). TLC was measured by placing regions of interest (ROIs) in the HCC and liver parenchyma. Mixed model ANOVAs and Bonferroni corrected post hoc tests were used for statistical analysis. RESULTS: Mean values for TLC were 132 ± 3.3 HU, 186 ± 5.8 HU and 168 ± 2.8 HU for protocols A, B and C. Protocol B provided significantly higher TLC than protocols A and C (p < 0.001). CONCLUSION: TLC was significantly higher using an imaging delay of 8 s compared with a delay of 4 or 12 s.


Asunto(s)
Angiografía/métodos , Yopamidol/análogos & derivados , Neoplasias Hepáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Medios de Contraste/administración & dosificación , Femenino , Humanos , Yopamidol/administración & dosificación , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
3.
J Endovasc Ther ; 19(2): 193-9, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22545884

RESUMEN

PURPOSE: To evaluate the frequency of type II endoleaks after endovascular aneurysm repair (EVAR) and to compare sac diameter and neck changes in patients with type II endoleak to endoleak-free patients with at least 3-year imaging follow-up. METHODS: Among 407 consecutive EVAR patients, 109 patients (101 men; mean age 72.1 years, range 55-86) had at least 3-year computed tomography (CT) data and no type I or III endoleak. In this cohort, 49 patients presented with a type II endoleak at some time and 60 patients had no endoleak. Patients with type II endoleaks were further divided into subgroups based on the vessel origin and the perfusion status (persistent or transient). The course of the perfusion status of type II endoleaks and changes in the aneurysm sac diameters, neck diameters, and renal to stent-graft distances (RSD) were evaluated in the defined groups. Reintervention and death rates were also reported. RESULTS: The mean follow-up was 68.1 ± 23.8 months. Compared to the no endoleak group, overall sac diameter increased significantly in the type II endoleak group (p = 0.007), but vessel origin did not have any influence. With regard to the perfusion status of type II endoleaks, aneurysm sac changes were significantly higher (p = 0.002) in the persistent endoleak group. During the study period, the increase in the proximal neck diameter was significantly higher in the no endoleak group compared to the type II endoleak group (p = 0.025). No significant difference was found in RSD changes between the defined groups. Reinterventions were performed in 20 (18.3%) patients (13 for type II endoleak); 2 (1.8%) patients without type II endoleak died of ruptured aneurysm. CONCLUSION: Persistent type II endoleaks led to significant aneurysm sac enlargement, but without increased mortality or rupture rates.


Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/efectos adversos , Endofuga/etiología , Procedimientos Endovasculares/efectos adversos , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/mortalidad , Rotura de la Aorta/etiología , Aortografía/métodos , Austria , Prótesis Vascular , Implantación de Prótesis Vascular/instrumentación , Implantación de Prótesis Vascular/mortalidad , Supervivencia sin Enfermedad , Endofuga/diagnóstico por imagen , Endofuga/mortalidad , Endofuga/terapia , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Diseño de Prótesis , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Stents , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
4.
Radiology ; 259(3): 757-66, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21436084

RESUMEN

PURPOSE: To compare the diagnostic performance (detection, local staging) of multiphasic 64-detector row computed tomography (CT) with that of gadobenate dimeglumine-enhanced 3.0-T magnetic resonance (MR) imaging in patients suspected of having pancreatic cancer. MATERIALS AND METHODS: The institutional review board approved this prospective study, and all patients provided written informed consent. Multidetector CT and MR imaging were performed in 89 patients (48 women aged 46-89 years [mean, 65.6 years] and 41 men aged 46-86 years [mean, 65.3 years]) suspected of having pancreatic cancer on the basis of findings from clinical examination or previous imaging studies. Two readers independently assessed the images to characterize lesions and determine the presence of focal masses, vascular invasion, distant metastases, and resectability. Findings from surgery, biopsy, endosonography, or follow-up imaging were used as the standard of reference. Logistic regression, the McNemar test, and κ values were used for statistical analysis. RESULTS: Focal pancreatic masses were present in 63 patients; 43 patients had adenocarcinoma. For reader 1, the sensitivities and specificities in the detection of pancreatic adenocarcinoma were 98% (42 of 43 patients) and 96% (44 of 46 patients), respectively, for CT and 98% (42 of 43 patients) and 96% (44 of 46 patients) for MR imaging. For reader 2, the sensitivities and specificities were 93% (40 of 43 patients) and 96% (44 of 46 patients), respectively, for CT and 95% (41 of 43 patients) and 96% (44 of 46 patients) for MR imaging. Vessel infiltration was determined in 22 patients who underwent surgery, and reader 1 obtained sensitivities and specificities of 90% (nine of 10 vessels) and 98% (119 of 122 vessels), respectively, for CT and 80% (eight of 10 vessels) and 96% (117 of 122 vessels) for MR imaging; for reader 2, those values were 70% (seven of 10 vessels) and 98% (120 of 122 vessels) for CT and 50% (five of 10 vessels) and 98% (120 of 122 vessels) for MR imaging. Both readers correctly assessed resectability in 87% (13 of 15 patients) of cases with CT and 93% (14 of 15 patients) of cases with MR imaging. Nonresectability was assessed correctly with CT in 75% (six of eight patients) of cases by reader 1 and 63% (five of eight patients) of cases by reader 2; nonresectability was correctly assessed with MR imaging in 75% (six of eight patients) of cases by reader 1 and 50% (four of eight patients) of cases by reader 2. None of the differences between modalities and readers were statistically significant (P > .05). CONCLUSION: Both CT and MR imaging are equally suited for detecting and staging pancreatic cancer. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101189/-/DC1.


Asunto(s)
Medios de Contraste , Imagen por Resonancia Magnética/métodos , Meglumina/análogos & derivados , Compuestos Organometálicos , Neoplasias Pancreáticas/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Yopamidol/análogos & derivados , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico por imagen , Estudios Prospectivos , Sensibilidad y Especificidad
5.
Eur Radiol ; 21(10): 2158-65, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21556908

RESUMEN

OBJECTIVE: The aim of this study was to assess whether visualisation of in-stent changes can be improved with high-resolution, steady-state, blood pool contrast-enhanced MR angiography compared with first-pass MR angiography. Intra-arterial digital subtraction angiography (DSA) served as the reference standard. METHODS: Twenty patients after stent placement in the superficial femoral artery (SFA) underwent MRA prior to reintervention. MRA of the SFA includes first-pass MRA as well as 3D high-resolution MRA in the steady state (SS-MRA) after injection of Gadofosveset trisodium. Sensitivity and specificity values for the detection of significant in-stent lesions by means of SS-MRA were calculated at the proximal, middle and distal stent segments in comparison to DSA. Kappa statistics were used to determine agreement between the two techniques. RESULTS: Sensitivity and specificity values for the detection of significant stenosis with SS-MRA reached 95% in the proximal, 100% in the middle and 100% in the distal stent segment. Kappa coefficients between SS-MRA and DSA were 0.789, 0.797 and 0.859 for the proximal, middle and distal segments, whereas the Kappa coefficients for FP-MRA were 0,211, 0,200 and 0,594 in these segments, respectively. CONCLUSION: Detection of in stent stenosis is significantly improved using SS MRA, in comparison to state-of-the-art FP-MRA.


Asunto(s)
Angiografía por Resonancia Magnética/métodos , Enfermedad Arterial Periférica/patología , Anciano , Anciano de 80 o más Años , Constricción Patológica , Medios de Contraste/farmacología , Femenino , Gadolinio/farmacología , Imagen de Acumulación Sanguínea de Compuerta/métodos , Humanos , Imagenología Tridimensional/métodos , Masculino , Persona de Mediana Edad , Compuestos Organometálicos/farmacología , Sensibilidad y Especificidad , Stents
6.
Eur Radiol ; 21(11): 2434-44, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21710265

RESUMEN

OBJECTIVE: To assess radiation dose and diagnostic image quality of a low-dose (80 kV) versus a standard-dose (120 kV) protocol for computed tomography angiography (CTA) of the supra-aortic arteries. METHODS: 64-slice CTA of the supra-aortic arteries was performed in 42 consecutive patients using randomly either 80 or 120 kV at 300 absolute mAs. Intravascular attenuation values, contrast-to-noise (CNR) and signal-to-noise ratio (SNR) measurements were performed at three levels. Two readers assessed image quality by using a four-point scale. The effective dose (ED) was calculated to assess the differences in radiation exposure. RESULTS: Intravascular attenuation values at 80 kV were higher in the common carotid artery, the carotid bifurcation and the internal carotid artery (p < 0.001). CNR and SNR differed at the internal carotid artery, with higher values in the 80-kV group (p > 0.05). Both readers revealed a significantly better image quality at 120 kV only at the common carotid artery (p < 0.001; p = 0.007). Mean ED was significantly lower at 80-kV (1.23 ± 0.09 vs. 3.99 ± 0.33 mSv; p < 0.001). CONCLUSION: Tube voltage reduction to 80 kV in CTA of the supra-aortic arteries allows for significant radiation dose reduction but has limitations at the level of the common carotid artery.


Asunto(s)
Angiografía/métodos , Aorta/patología , Arterias Carótidas/patología , Radiometría/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Estudios Prospectivos
7.
AJR Am J Roentgenol ; 197(5): 1251-7, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22021522

RESUMEN

OBJECTIVE: The purpose of our study was to compare high-resolution gadofosveset-enhanced MR angiography (MRA) with the reference standard CT angiography (CTA) in planning endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms. SUBJECTS AND METHODS: Thirty consecutive patients were included in this prospective study. CTA was performed routinely before EVAR for stent-graft implantation planning and selection. In addition, first-pass and, after a delay of 10 minutes, steady-state MRA were performed using the blood pool contrast agent gadofosveset for study purposes. Standard diameter and length parameters for stent-graft evaluation rendered from CTA and MRA were compared. According to the results of MRA measurements, stent-grafts were selected for each patient and compared with the device actually implanted. Image quality was assessed using subjective image quality parameters. RESULTS: Diameter and length measurements showed small but significant differences (p < 0.001) between MRA and CTA. Stent-graft selection according to these measurements showed 100% concordance between both modalities. Subjective imaging parameters showed significantly better results for CTA compared with MRA (p < 0.001). CONCLUSION: In this study, MRA using a blood pool contrast agent has shown the ability to provide reliable and exact measurements before EVAR, allowing noninvasive planning of the intervention despite lower image-quality and without the disadvantages of ionizing radiation and nephrotoxicity.


Asunto(s)
Angiografía/métodos , Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular , Medios de Contraste/administración & dosificación , Gadolinio/administración & dosificación , Angiografía por Resonancia Magnética/métodos , Compuestos Organometálicos/administración & dosificación , Planificación de Atención al Paciente , Stents , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Yopamidol/administración & dosificación , Yopamidol/análogos & derivados , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estadísticas no Paramétricas , Resultado del Tratamiento
8.
Eur Radiol ; 20(9): 2084-91, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20397019

RESUMEN

OBJECTIVE: To evaluate coronary stents in vitro using 128-slice-dual-source computed tomography (CT). METHODS: Twelve different coronary stents placed in a non-moving cardiac/chest phantom were examined by 128-slice dual-source CT using three CT protocols [high-pitch spiral (HPS), sequential (SEQ) and conventional spiral (SPIR)]. Artificial in-stent lumen narrowing (ALN), visible inner stent area (VIA), artificial in-stent lumen attenuation (ALA) in percent, image noise inside/outside the stent and CTDIvol were measured. RESULTS: Mean ALN was 46% for HPS, 44% for SEQ and 47% for SPIR without significant difference. Mean VIA was similar with 31% for HPS, 30% for SEQ and 33% for SPIR. Mean ALA was, at 5% for HPS, significantly lower compared with -11% for SPIR (p = 0.024), but not different from SEQ with -1%. Mean image noise was significantly higher for HPS compared with SEQ and SPIR inside and outside the stent (p < 0.001). CTDIvol was lower for HPS (5.17 mGy), compared with SEQ (9.02 mGy) and SPIR (55.97 mGy), respectively. CONCLUSION: The HPS mode of 128-slice dual-source CT yields fewer artefacts inside the stent lumen compared with SPIR and SEQ, but image noise is higher. ALN is still too high for routine stent evaluation in clinical practice. Radiation dose of the HPS mode is markedly (less than about tenfold) reduced.


Asunto(s)
Algoritmos , Prótesis Vascular , Angiografía Coronaria/métodos , Vasos Coronarios/cirugía , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Stents , Tomografía Computarizada por Rayos X/métodos , Humanos , Fantasmas de Imagen , Intensificación de Imagen Radiográfica/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
9.
Oncologist ; 14(1): 70-6, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19144684

RESUMEN

BACKGROUND: Few data are available on the safety and efficacy of sorafenib in patients with multifocal hepatocellular carcinoma (HCC) and advanced liver cirrhosis. METHODS: Between May 2006 and December 2007, we treated 59 patients (Child-Pugh class A/B/C, 26/23/10) with unresectable HCC with sorafenib (daily target dose, 400 mg twice daily). Data were collected retrospectively. Survival curves were calculated via the Kaplan-Meier method. RESULTS: One patient (Child-Pugh class B) had a partial response, 14 patients (Child-Pugh class A/B/C, 5/7/2) had stable disease, and 32 patients (Child-Pugh class A/B/C, 15/11/6) had progressive disease; 12 patients were not evaluable because they had no follow-up radiologic evaluation. In the intention-to-treat group, the median time to progression and overall survival (OS) time were 2.8 months (range, 1.4-6.5 months) and 6.5 months (range, 0.4-17.4 months), respectively. Well-preserved liver function and lower Barcelona Clinic Liver Cancer stage were associated with a longer OS time on univariate analysis. There were four severe gastrointestinal bleedings (grade 4-5; Child-Pugh class B/C, 2/2). Most drug-related side effects were low grade and manageable irrespective of liver function. CONCLUSIONS: Sorafenib is effective and safe in patients with multifocal HCC and Child-Pugh class A cirrhosis. Survival in Child-Pugh class B patients is significantly less than in Child-Pugh class A patients, warranting a prospective randomized trial with a placebo group. Child-Pugh class C patients have a limited life expectancy despite sorafenib treatment because of their severe underlying disease and derive little benefit from sorafenib treatment.


Asunto(s)
Antineoplásicos/uso terapéutico , Bencenosulfonatos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Piridinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Bencenosulfonatos/efectos adversos , Carcinoma Hepatocelular/complicaciones , Femenino , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/efectos adversos , Sorafenib
10.
Arab J Urol ; 16(2): 218-223, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29892486

RESUMEN

Partial penectomy (glansectomy with/or without distal corporectomy) is an acceptable alternative for smaller distal pT3 penile carcinoma lesions in highly motivated and compliant patients. The authors describe a novel technique of neo-glans reconstruction using a tunica vaginalis (TV) testis allograft. However, due to an unclear resection margin on final histology, the patient underwent re-do surgery with a neo-glans revision using the well-established mesh split-thickness skin graft (STSG) technique. The penile length was preserved and the penile and bulbar part of the urethra was additionally mobilised in order to obtain a natural and aesthetic result for the meatus. Neo-glans reconstruction with TV coverage may be another promising alternative, which certainly requires further evaluation. We believe that the donor-site associated morbidity is minimal when compared to other harvesting sites. However, this is just an assumption, because direct comparison data on grafting techniques and neo-glans reconstruction are not available. Nevertheless, we think that for re-do procedures a standardised approach using a STSG technique should be the treatment method of choice.

11.
Radiographics ; 27(2): 431-54, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17374862

RESUMEN

Thin-section multi-detector row computed tomographic (CT) colonography is a powerful tool for the detection and classification of colonic lesions. However, each step in the process of a CT colonographic examination carries the potential for misdiagnosis. Suboptimal patient preparation, CT scanning protocol deficiencies, and perception and interpretation errors can lead to false-positive and false-negative findings, adversely affecting the diagnostic performance of CT colonography. These problems and pitfalls can be overcome with a variety of useful techniques and observations. A relatively clean, dry, and well-distended colon can be achieved with careful patient preparation, thereby avoiding the problem of residual stool and fluid. Knowledge of the morphologic and attenuation characteristics of common colonic lesions and artifacts can help identify bulbous haustral folds, impacted diverticula, an inverted appendiceal stump, or mobile polyps, any of which may pose problems for the radiologist. A combined two-dimensional and three-dimensional imaging approach is recommended for each colonic finding. A thorough knowledge of the various pitfalls and pseudolesions that may be encountered at CT colonography, along with use of dedicated problem-solving techniques, will help the radiologist differentiate between definite colonic lesions and pseudolesions.


Asunto(s)
Artefactos , Neoplasias del Colon/diagnóstico por imagen , Colonografía Tomográfica Computarizada/instrumentación , Colonografía Tomográfica Computarizada/métodos , Pólipos/diagnóstico por imagen , Intensificación de Imagen Radiográfica/métodos , Diagnóstico Diferencial , Humanos , Guías de Práctica Clínica como Asunto
12.
Neuromolecular Med ; 18(3): 378-95, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27455862

RESUMEN

Dementia contributes substantially to the burden of disability experienced at old age, and mitochondrial dysfunction (MD) was identified as common final pathway in brain aging and Alzheimer's disease. Due to its early appearance, MD is a promising target for nutritional prevention strategies and polyphenols as potential neurohormetic inducers may be strong neuroprotective candidates. This study aimed to investigate the effects of a polyphenol-rich grape skin extract (PGE) on age-related dysfunctions of brain mitochondria, memory, life span and potential hormetic pathways in C57BL/6J mice. PGE was administered at a dose of 200 mg/kg body weight/d in a 3-week short-term, 6-month long-term and life-long study. MD in the brains of aged mice (19-22 months old) compared to young mice (3 months old) was demonstrated by lower ATP levels and by impaired mitochondrial respiratory complex activity (except for mice treated with antioxidant-depleted food pellets). Long-term PGE feeding partly enhanced brain mitochondrial respiration with only minor beneficial effect on brain ATP levels and memory of aged mice. Life-long PGE feeding led to a transient but significant shift of survival curve toward higher survival rates but without effect on the overall survival. The moderate effects of PGE were associated with elevated SIRT1 but not SIRT3 mRNA expressions in brain and liver tissue. The beneficial effects of the grape extract may have been influenced by the profile of bioavailable polyphenols and the starting point of interventions.


Asunto(s)
Memoria/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Extractos Vegetales/farmacología , Vitis/química , Envejecimiento , Animales , Encéfalo/patología , Longevidad/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Mitocondrias/fisiología
13.
J Clin Endocrinol Metab ; 90(4): 2175-8, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15634723

RESUMEN

BACKGROUND: Elevated plasma asymmetrical dimethylarginine (ADMA) is suggested to contribute to hyperhomocyst(e)ine-related vascular dysfunction in patients with peripheral artery disease (PAD). The present trial investigated whether homocyst(e)ine (Hcy)-lowering therapy with vitamin-B (vit-B) and folic acid affects plasma concentrations of ADMA in patients with PAD and hyperhomocyst(e)inemia. SUBJECTS AND METHODS: Forty-nine subjects (15 women, 34 men) with PAD and fasting plasma total Hcy concentrations greater than 15 micromol/liter were randomized to receive either oral vit-B and folic acid therapy (n = 27) or placebo (n = 22) for 6 wk. Fasting venous blood samples were monitored for plasma total Hcy, vit-B12 and folate, ADMA, symmetric dimethylarginine, L-arginine, and high-sensitivity C-reactive protein. RESULTS: After 6 wk, plasma Hcy concentrations were decreased, and concentrations of vit-B12 and folate were elevated in patients with vitamin supplementation (all P < 0.05 vs. baseline) and unchanged in the placebo group. Dimethylarginine plasma concentrations were not affected by treatment. High-sensitivity C-reactive protein correlated with ADMA plasma concentrations (r = 0.29; P < 0.01). CONCLUSION: The lack of vit-B and folic acid therapy on plasma concentrations of ADMA renders a role of extracellular methylarginines unlikely to be involved in the pathophysiology of hyperhomocyst(e)inemia and its complications.


Asunto(s)
Arginina/análogos & derivados , Arginina/sangre , Ácido Fólico/administración & dosificación , Hiperhomocisteinemia/tratamiento farmacológico , Enfermedades Vasculares Periféricas/sangre , Complejo Vitamínico B/administración & dosificación , Anciano , Método Doble Ciego , Femenino , Humanos , Hiperhomocisteinemia/sangre , Masculino , Persona de Mediana Edad
14.
Magn Reson Imaging ; 23(6): 739-44, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16198829

RESUMEN

Over the past decade, a number of interventions for durable cartilage repair have emerged. Magnetic resonance (MR) tomography is an excellent noninvasive method for monitoring cartilage repair tissues throughout the postsurgical period. However, evaluating cartilage morphology after matrix-based autologous cartilage implantation (ACI) with MR imaging (MRI) still remains a challenge. In this study, we combined a high-resolution cartilage-sensitive fast-spin echo (FSE) sequence with intravenous application of a contrast agent for enhancing synovial fluid. Two independent musculoskeletal radiologists interpreted the pictures for the thickness, length and surface of the cartilage implants. A multivariate two-way analysis of variance with two repeated measures was performed and showed that evaluation of cartilage implant morphology was significantly improved after the application of gadodiamide on proton density FSE images. Contrast-enhanced MRI of articular cartilages is a promising technique in the postoperative follow-up of patients after ACI.


Asunto(s)
Cartílago Articular/patología , Cartílago Articular/trasplante , Fracturas del Cartílago/patología , Fracturas del Cartílago/cirugía , Traumatismos de la Rodilla/patología , Traumatismos de la Rodilla/cirugía , Imagen por Resonancia Magnética/métodos , Adulto , Cartílago Articular/lesiones , Medios de Contraste , Femenino , Gadolinio DTPA , Humanos , Aumento de la Imagen/métodos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
15.
Magn Reson Imaging ; 23(7): 779-87, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16214608

RESUMEN

OBJECTIVE: Monitoring of articular cartilage repair after matrix-associated autologous chondrocyte implantation (MACI) by a new grading and point-scale system based on noninvasive cartilage-specific magnetic resonance imaging (MRI) protocol. PATIENTS AND METHODS: In 20 patients, postoperative high-resolution MRI follow-up examinations at 4, 12, 24 and 52 weeks after matrix-based ACI for cartilage repair were initiated. The repair tissue was described with separate variables: degree of defect repair in width and length, surface, structure and signal intensity of the repair tissue, and status of the subchondral lamina and bone. For these variables, a grading system with point-scale evaluation was applied, and the mean average values were calculated for every follow-up MR exam of each patient. RESULTS: In 10 patients, an incomplete filling of the defect improved to complete filling (6 patients) or less incomplete (4 patients) filling of the defect. Three cases of implant hypertrophy returned to normal within 1 year. Complete filling of the defect by repair tissue was found in 2 patients from the beginning. Integration was complete in 10 cases. Improvement of incomplete to complete integration was found in 3 patients. The signal intensity of the implant developed to native cartilage signal in 13 patients. The mean average values increased from the 4th to the 52 nd week in 17 of 20 patients and decreased in 3 of 20 patients. CONCLUSION: High-resolution MRI provides a noninvasive tool for monitoring the development of cartilage repair tissue in MACI over time and helps to differentiate abnormal repair tissue from a normal maturation process.


Asunto(s)
Enfermedades de los Cartílagos/terapia , Condrocitos/trasplante , Traumatismos de la Rodilla/terapia , Imagen por Resonancia Magnética/métodos , Adulto , Cartílago Articular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante Autólogo , Resultado del Tratamiento
16.
PLoS One ; 9(6): e99832, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24919195

RESUMEN

OBJECTIVE: To prospectively evaluate image quality and radiation dose using a low-dose computed tomography angiography protocol and iterative image reconstruction for high-pitch dual-source CT-angiography (DSCTA) of the supraaortic arteries. MATERIAL AND METHODS: DSCTA was performed in 42 patients, using either 120 kVp tube voltage, 120 mAS tube current, 2.4 pitch and filtered back projection, or 100 kVp tube voltage, 100 mAs tube current, 3.2 pitch, and sinogram affirmed iterative reconstruction. Measurements of vessel attenuation, of the contrast-to-noise ratio (CNR) and the signal-to-noise ratio (SNR) were performed to objectively evaluate image quality. Two readers evaluated subjective image quality and image noise, using a four-point scale. Effective dose was used to compare the differences in radiation dose. RESULTS: Low-dose protocol application showed significantly higher vessel opacification (p = 0.013), and non-significantly higher CNR and SNR values. There was no difference in the subjective image quality and image noise reading between the protocols. Effective dose was significantly lower using the low-dose protocol (1.29 ± 0.21 mSv vs. 2.92 ± 0.72 mSv; p < 0.001). CONCLUSION: The combined use of reduced tube voltage, reduced tube current, and iterative reconstruction reduces radiation dose by 55.4% in high-pitch DSCTA of the supraaortic arteries without impairment of image quality.


Asunto(s)
Angiografía/métodos , Arterias/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Dosis de Radiación , Cintigrafía , Relación Señal-Ruido
17.
Ann Thorac Surg ; 95(5): 1577-83, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23566647

RESUMEN

BACKGROUND: The aim of this analysis was to assess short and mid-term results of patients undergoing thoracic endovascular aortic repair (TEVAR) for 4 different indications. METHODS: From 1996 to 2010, 300 patients (80 female, 220 male, median age 67 years [20 to 88]) underwent TEVAR at our department. Among them were 137 descending thoracic aneurysms (DTA), 80 type B dissections (60 acute, 20 chronic), 59 perforating aortic ulcer (PAU), and 24 traumatic aortic transections (ATAT). Hospital mortality and mid-term survival among different indications for TEVAR were evaluated. RESULTS: Overall hospital mortality in our series was 5% (n = 15). Seven patients with DTA (5%), 4 patients with type B dissections (5%), 2 patients with PAU (3.4%), and 2 ATAT (8%) patients died during their hospital stay. Kaplan-Meier survival analysis revealed significant differences in survival rates according to the various indications for TEVAR (p < 0.001). Overall long-term mortality was 86%, 63%, and 44% at 1, 5, and 10 years. Early and late endoleak rate was 18% and 8%, respectively. CONCLUSIONS: The TEVAR has evolved into a safe and effective therapy for different aortic pathology resulting in promising long-term results. Nevertheless, the indication for TEVAR has direct impact on the success of the procedure. Patients with acute type B aortic dissections and acute traumatic aortic lesions seem to benefit the most from TEVAR.


Asunto(s)
Aorta Torácica/cirugía , Procedimientos Endovasculares/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Disección Aórtica/mortalidad , Disección Aórtica/cirugía , Aneurisma de la Aorta Torácica/mortalidad , Aneurisma de la Aorta Torácica/cirugía , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo
18.
Eur J Radiol ; 81(9): 2304-7, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21620601

RESUMEN

Primary hyperaldosteronism due to aldosterone secreting adrenal adenomas is an important and potentially curable cause for hypertension. The differentiation between unilateral or bilateral adrenal adenomas is crucial, as unilateral adenomas can easily be cured by surgery whereas bilateral adenomas have to be treated conservatively. Exact diagnosis can be made when unilateral or bilateral hormone production is proven with adrenal vein sampling. We present an effective step-by-step technique how to perform an adrenal vein sampling with a special emphasis on how to reliably catheterize the right adrenal vein using Dyna CT.


Asunto(s)
Glándulas Suprarrenales/irrigación sanguínea , Glándulas Suprarrenales/cirugía , Biomarcadores de Tumor/sangre , Flebografía/métodos , Radiografía Intervencional/métodos , Tomografía Computarizada por Rayos X/métodos , Humanos
19.
Eur J Radiol ; 81(9): 2265-9, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21703792

RESUMEN

BACKGROUND: Multidetector CT angiography (CTA) is a non-invasive imaging technique for evaluation of peripheral vascular disease. CTA might be particularly useful for assessment of intermediate- and long-term morphological outcome after endovascular treatment. Validation of CTA vs. the current imaging standard, colour Doppler ultrasonography (CDUS), for quantification of native and in-stent re-stenosis in the superficial femoral artery (SFA) is required. METHODS: Seventy randomized patients who underwent stent implantation (n=47) or balloon angioplasty (n=23) underwent 6-month follow-up with CDUS and CTA. CTA was compared with CDUS in both sub-groups of patients in terms of binary re-stenosis (>50% lumen narrowing) and re-occlusion. Agreement between CTA and CDUS was assessed using Kappa (κ) statistics with 95% confidence intervals, and correlation coefficients. RESULTS: Binary re-stenosis was detected in 16/70 (22.9%) patients by CTA and 17/70 (24.3%) patients by CDUS (κ=0.88, 95% CI: 0.80-0.96). Re-stenosis rates after balloon angioplasty were 39.1% (9/23) on CTA and CDUS (κ=0.82, 95% CI: 0.66-0.98), and after stent implantation 14.9% (7/47) on CTA and 17.0% (8/47) on CDUS (κ=0.92, 95% CI: 0.84-1.00). Re-occlusions were detected in 3/70 (4.3%) patients by both CTA and CDUS (κ=0.65; 95% CI 0.54-0.76). Significant correlations (r=0.85, p<0.001) were noted between degree of re-stenosis on CTA and peak velocity ratio on CDUS. The correlation coefficient was higher in patients after balloon angioplasty (r=0.94, p<0.001) than in patients after stent implantation (r=0.71, p<0.001). CONCLUSION: CTA and CDUS show excellent agreement for evaluation of native and in-stent re-stenosis after endovascular treatment of SFA obstructions. CTA is an appropriate non-invasive imaging modality for follow-up after endovascular therapy.


Asunto(s)
Angiografía/métodos , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/cirugía , Oclusión de Injerto Vascular/diagnóstico por imagen , Stents/efectos adversos , Tomografía Computarizada por Rayos X/métodos , Ultrasonografía/métodos , Anciano , Femenino , Oclusión de Injerto Vascular/etiología , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
20.
Eur J Radiol ; 81(7): 1589-94, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21536397

RESUMEN

PURPOSE: To compare perioperative and follow-up outcomes of symptomatic versus asymptomatic patients following endovascular repair of anastomotic pseudoaneurysms (APAs) of the abdominal aorta and iliac arteries. METHODS: We retrospectively evaluated 17 patients (two women), with a mean age of 66.2 years (range 30-83 years). Endovascular treatment was performed in ten symptomatic, and seven asymptomatic patients electively. Data included technical success, perioperative (within 30 days) mortality and morbidity, as well as stent graft-related complications, reinterventions, and survival in follow-up. RESULTS: Bifurcated (n = 13), aortomonoiliac (n = 3) endoprosthesis and one aortic cuff were implanted with a primary technical success rate of 100%. The overall in-hospital mortality and morbidity rate was 11.8% and 35.3%. The mean survival was 36.5 (range 0-111) months. There was a clear trend toward a lower overall survival within hospital and at one and three years for symptomatic patients compared to asymptomatic patients. (47.7 (CI: 0-138.8) versus 52.6 (CI: 28.5-76.8) months (p = 0.274)). During follow-up, late stent graft related complications were observed in six patients (35.3%) necessitating eight endovascular reinterventions. Additional three patients with primary fistulas between the APA and the intestine were treated by late surgical revision. CONCLUSION: Endovascular therapy of APAs represents a considerable alternative to open surgical repair. Short proximal anchoring zones still pose a risk for endoleaks and unintentional overstenting of side branches with commercially available devices, but this might be overcome by use of fenestrated and branched stent grafts in elective cases.


Asunto(s)
Aneurisma Falso/etiología , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma Ilíaco/cirugía , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica , Aneurisma Falso/mortalidad , Aneurisma Falso/terapia , Aneurisma de la Aorta Abdominal/mortalidad , Implantación de Prótesis Vascular , Femenino , Mortalidad Hospitalaria , Humanos , Aneurisma Ilíaco/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/terapia , Estudios Retrospectivos , Estadísticas no Paramétricas , Stents , Tasa de Supervivencia , Resultado del Tratamiento
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