RESUMEN
Klippel-Trénaunay syndrome (KTS) is a rare congenital anomaly characterized by malformation of lymph and blood vessels as well as growth disturbance of soft tissue and bone. The clinical picture is variable and associated with an increased risk of thromboembolic events mediated by intravascular coagulopathy in venous malformations. Here, we report on a male patient with KTS suffering from recurrent deep vein thrombosis (DVT) and life-threatening bleeding due to consumptive coagulopathy. Furthermore, we describe the successful long-term anticoagulant management with rivaroxaban.
Asunto(s)
Anticoagulantes/administración & dosificación , Coagulación Intravascular Diseminada/tratamiento farmacológico , Factor Xa/administración & dosificación , Síndrome de Klippel-Trenaunay-Weber/complicaciones , Morfolinas/administración & dosificación , Tiofenos/administración & dosificación , Adolescente , Coagulación Intravascular Diseminada/etiología , Humanos , Masculino , RivaroxabánRESUMEN
PURPOSE: To assess thyroid perfusion in patients with autoimmune thyroid diseases compared with that in healthy control subjects by using an arterial spin-labeling (ASL) magnetic resonance (MR) technique and to assess whether thyroid perfusion is associated with endocrine laboratory abnormalities. MATERIALS AND METHODS: This study was approved by the local institutional review board. All participants gave written informed consent. Perfusion imaging of the thyroid gland was performed in 10 patients with Graves disease (GD) and 10 patients with Hashimoto thyroiditis (HT). Ten healthy individuals served as control subjects. Perfusion imaging was performed with a 1.5-T MR unit by using a flow-sensitive alternating inversion recovery-true fast imaging with steady-state precession technique. Perfusion maps of the entire thyroid gland were calculated on the basis of extended Bloch equations. Analysis of variance with a post hoc test (Tukey honestly significant difference) was performed to assess differences in perfusion between groups. Associations between perfusion and laboratory parameters were analyzed with univariate regression analysis. RESULTS: Mean thyroid perfusion was 1596 mL/min/100 g +/- 436 (standard deviation) in patients with GD, 825 mL/min/100 g +/- 264 in patients with HT, and 491 mL/min/100 g +/- 89 in healthy control subjects. Perfusion was significantly higher in patients with GD (P < .0001) and those with HT (P < .05) than in control subjects. A significant difference in thyroid perfusion was detected between the two autoimmune entities (P < .0001). In patients with GD, significant associations were found between perfusion and serum concentrations of free thyroid hormones and anti-thyroid-stimulating hormone receptor antibodies (P < .05 for all). CONCLUSION: Quantitative ASL perfusion imaging of the thyroid gland revealed significant perfusion differences in the autoimmune thyroid diseases GD and HT. Absolute quantification of thyroid perfusion may be useful in the clinical assessment of autoimmune thyroid disorders and when monitoring therapeutic treatment in GD.
Asunto(s)
Angiografía por Resonancia Magnética , Marcadores de Spin , Glándula Tiroides/irrigación sanguínea , Tiroiditis Autoinmune/diagnóstico , Adulto , Femenino , Enfermedad de Graves/diagnóstico , Enfermedad de Hashimoto/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Glándula Tiroides/patología , Adulto JovenRESUMEN
Monocyte-chemoattractant-protein (MCP)-1 and its receptor CCR2 have been shown to play a pivotal role in vascular inflammation and atherosclerotic plaque formation. However, it is currently unclear whether MCP-1/CCR2 triggered inflammation affects nitric oxide (NO)-bioavailability, hence influencing vascular function, a sign of early atherosclerosis. Therefore, we sought to investigate the association between serum levels of MCP-1 and NO-bioavailability, expressed as flow mediated dilation (FMD) in vivo, and the impact of CCR2 gene variations on FMD. We studied a German population of 242 prediabetic individuals (144 women, 98 men; mean age 45+/-0.8 years) via FMD by high-resolution ultrasound (13MHz). In order to replicate our findings, a second, independent population (n=115; 44 women, 77 men; mean age 48+/-1.0 years) (total=357 individuals) from Italy was studied. Vascular function in the Italian population was studied via intra-arterial application of acetylcholine. MCP-1 serum-levels were assessed by ELISA and CCR2 polymorphisms were determined by sequencing. MCP-1 serum levels showed no association with FMD (p=0.90), whereas the CCR2 promoter polymorphism was associated with elevated FMD (T/T: 5.6+/-0.3%; T/A: 6.7+/-0.4%; A/A: 8.3+/-0.8%; p=0.01) after adjusting for possible confounders. These results were confirmed in the independent Italian population (A/A: 97.1+/-20.3 vs. T/T: 60.5+/-5.6% forearm blood-flow increase; p<0.05). When testing for the functional relevance of the T-960A (rs3918359) polymorphism, we found that the A/A-genotype was associated with moderately increased protein binding in EMSA, increased promoter activity in luciferase assays and reduced transendothelial monocyte migration. In conclusion, MCP-1 serum levels do not reflect endothelial function in vivo in prediabetic individuals. However, the functionally relevant CCR2 promoter polymorphism T-960A (rs3918359) is associated with elevated vascular function. This might be due to reduced subendothelial inflammation, mediated by reduced transendothelial monocyte-migration ability.
Asunto(s)
Aterosclerosis/genética , Endotelio Vascular/fisiopatología , Polimorfismo Genético , Estado Prediabético/sangre , Estado Prediabético/fisiopatología , Receptores CCR2/sangre , Receptores CCR2/genética , Adulto , Circulación Sanguínea/genética , Movimiento Celular , Ensayo de Cambio de Movilidad Electroforética , Femenino , Genotipo , Haplotipos , Humanos , Luciferasas/genética , Masculino , Persona de Mediana Edad , Monocitos , Regiones Promotoras Genéticas/genética , Vasodilatación/genéticaAsunto(s)
Paraparesia/diagnóstico , Tirotoxicosis/diagnóstico , Adulto , Humanos , Parálisis Periódica Hipopotasémica/etiología , Angiografía por Resonancia Magnética/métodos , Masculino , Marcadores de Spin , Glándula Tiroides/diagnóstico por imagen , Tirotoxicosis/diagnóstico por imagen , UltrasonografíaRESUMEN
Single low density lipoprotein (LDL) fibrinogen apheresis has shown beneficial effects in the treatment of patients with sudden sensorineural hearing loss (SSHL). Pathophysiologically, a microcirculatory disorder of the inner ear, probably caused by disturbed endothelial function, is discussed as a final common pathway of a variety of SSHL etiologies. Thus, we carried out a prospective pilot study on the efficacy of Rheopheresis on vascular function in these patients, embedded into an ongoing randomized controlled multicenter trial investigating the efficacy of Rheopheresis for the treatment of SSHL. Potential modulation of systemic endothelial dysfunction by Rheopheresis was examined by measuring flow-associated vasodilatation of the brachial artery (according to the criteria of the American College of Cardiology) in a small group of patients suffering from SSHL (N=6, 5m/1f, mean age 56+/-11 years) within the last 3 days. At baseline, five of the six patients with acute hearing loss showed endothelial dysfunction as evidenced by diminished flow-mediated vasodilatation (FMD<5%). After a single Rheopheresis treatment, flow-mediated vasodilatation improved significantly (from 3.9+/-3.6% to 7.2+/-2.4%, P=0.05, mean+/-SD, two-sided paired T-test). This was paralleled by a reduction in fibrinogen (364+/-216 mg/dL to 142+/-96 mg/dL, P=0.03), total cholesterol (228+/-23 to 98+/-10, P<0.0001) and LDL cholesterol levels (153+/-8 mg/dL to 83+/-23 mg/dL, P<0.01). Based on this case series we conclude that single Rheopheresis treatment might have an acute beneficial effect on endothelial dysfunction in patients suffering from SSHL.
Asunto(s)
Eliminación de Componentes Sanguíneos , Pérdida Auditiva Súbita/terapia , Proteínas Sanguíneas , Endotelio Vascular/fisiopatología , Femenino , Pérdida Auditiva Súbita/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios ProspectivosRESUMEN
Reduced bio-availability of nitric oxide leading to disturbed flow mediated (endothelial dependent) vasodilation (FMD) has been shown to be an early functional abnormality of the vascular system in insulin resistant individuals and other subjects at high risk for accelerated atherosclerosis. In addition, an increase of the intima-media thickness (IMT) is regarded as an early marker of morphological alterations of the vessel wall. Whether endothelial dysfunction (ED) is evident already at an early stage when morphological changes of the vessel wall are not apparent is still an open question. We, therefore, examined IMT and peripheral endothelial function in a group of young insulin resistant subjects in a cross-sectional study and compared these results with a metabolically healthy (insulin sensitive) control group. We measured IMT (distal common carotid arteries), endothelium-dependent and endothelium-independent vasodilation (flow mediated and glyceroltrinitrate induced vasodilation of the brachial artery) non-invasively with high resolution ultrasound (13 MHz) in 91 young normoglycemic subjects (40/51 M/F, median: 31 years, range 18-50 years). Insulin sensitivity was measured with a euglycemic, hyperinsulinemic glucose clamp. Despite a marked reduction in flow-mediated vasodilation in insulin resistant (IR) subjects (FMD: median 3.4%, range -4.0 to 12.5 in IR versus 6.6%, range -1.2 to 20.1% in insulin sensitive subjects; P = 0.017), there was no difference in endothelial independent vasodilation (16.3%, range 5.7-41.0% versus 16.1%, range 0.5-39.2%) and in IMT (0.50 mm, range 0.39-0.66 and 0.51, 0.40-0.70 mm, respectively). These data suggest that ED can be detected very early in the life of insulin resistant subjects whereas no significant structural changes, indicated by a thickening of the intima-media layer, could be found. We therefore conclude that for identification of subjects with a high risk for accelerated atherosclerosis at an early stage, measurement of flow mediated vasodilation of the brachial artery may be more helpful than measuring thickness of the vascular wall.
Asunto(s)
Enfermedades de las Arterias Carótidas/patología , Endotelio Vascular/patología , Endotelio Vascular/fisiología , Resistencia a la Insulina , Enfermedades Vasculares Periféricas/patología , Túnica Media/patología , Adolescente , Adulto , Factores de Edad , Análisis de Varianza , Enfermedades de las Arterias Carótidas/etiología , Enfermedades de las Arterias Carótidas/fisiopatología , Arteria Carótida Común , Estudios de Casos y Controles , Estudios Transversales , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/etiología , Enfermedades Vasculares Periféricas/fisiopatología , Probabilidad , Medición de Riesgo , Índice de Severidad de la Enfermedad , VasodilataciónRESUMEN
BACKGROUND: Recent theory in pathogenesis of atherosclerosis has focused on the pathobiology of the artery wall including the emerging influence of the nitric oxide (NO) system on thrombogenicity and trigger mechanisms leading to morphologic changes culminating in the stenotic plaque. Therefore, diagnostic evaluation of disturbances in NO bioavailability might be of prognostic relevance regarding primary prevention of cardiovascular disease. Disturbances in NO production can be measured noninvasively with conventional high-resolution ultrasound. On the other hand, particularly in individuals with diabetes, microalbuminuria is thought to be associated with an increased risk of cardiovascular events. Thereby it is still unknown, whether an increase in renal albumin excretion can be regarded as an indicator of global endothelial dysfunction, or whether other partial functions such as the nitric oxide system might be disturbed earlier. PROBANDS AND METHODS: Therefore, the NO system and renal albumin excretion were examined in 129 subjects (56 with type 2 diabetes and 73 nondiabetics). Nitric oxide production was assessed by measuring flow-mediated vasodilatation (FMD) of the brachial artery using a 13-MHz linear array. Comparison was done between subjects with disturbed endothelial NO production (FMD < 5%) and subjects with normal regulation of the vascular tone (FMD > 5%). RESULTS: In normoalbuminuric individuals (< 20 microg/min, and < 20 mg/l, respectively), neither for the group of subjects with type 2 diabetes nor in the group of nondiabetics, relevant differences could be found in renal albumin excretion (RAE) rate between subjects with disturbed and normal FMD (RAE in diabetics 4.8 +/- 5.5 vs. 4.6 +/- 5.1 mg/l and in nondiabetics 5.1 +/- 2.6 vs. 4.9 +/- 2.7 microg/min). Both groups were well balanced regarding other risk factors of the metabolic syndrome (systolic/diastolic blood pressure, glucose and lipid metabolism). Furthermore, comparison of FMD in subjects with microalbuminuria (20-200 microg/min and 20-200 mg/l, respectively, n = 18) versus normoalbuminuric individuals (n = 111) again did not reveal a significant difference for the diabetic group (FMD median 4.3% [range 1.8-7.6%] vs. 5.0% [range 1.1-9.1%]) nor for the nondiabetic group (FMD median 4.7% [range 3.1-13.3%] vs. 5.2% [range -1.2-31.6%]). However, this analysis underlined the considerable influence of the classic cardiovascular risk factors. Particularly in the nondiabetic group, individuals with microalbuminuria showed higher blood pressure (p = 0.05) and a higher body mass index (p < 0.01). CONCLUSION: From these results, it is concluded that both procedures (renal albumin excretion rate and the measurement of endothelium-dependent vasodilatation) investigate two independent disturbances of the vascular wall. Furthermore, these results lead to the hypothesis that disturbances in endothelial NO production occur early and may already be operative before renal albumin excretion increases. Thus, for the purpose of actually identifying cardiovascular high-risk subjects early, peripheral endothelial dysfunction should be measured in addition to renal albumin excretion rate.