RESUMO
Turner syndrome (TS) is a common genetic disorder in females with high incidence of ascending aortic dilatation and even dissection occurring as early as in the second decade. Known risk factors (RF) are bicuspid aortic valves (BAV), coarctation of the aorta (CoA), and arterial hypertension. Since 10% of dissections occur in patients without RF, an intrinsic aortic wall abnormality has been postulated. This study aimed to investigate the elasticity of the ascending aorta as a surrogate marker of aortic wall texture. Forty-six pediatric patients with genetically proven TS were prospectively examined for the morphology of their aortic valve, and size and elasticity indices of the adjacent aorta. Cohorts of 46 female subjects with tricuspid aortic valves (TAV) and ten non-syndromic females with BAV were investigated as separate control groups. Comparison of healthy controls with TS patients revealed significantly deteriorated elasticity indices in those with TS. Furthermore, normalized aortic dimensions were greater in TS patients, but dilatations of the ascending aorta with z-score levels above two were restricted to those with BAV (14/46). Deteriorated elasticity indices were measured in TS patients, independent of aortic dilatation, BAV, and CoA, and were comparable to those of patients with isolated, non-syndromic BAVs. By measuring elasticity levels as a surrogate for aortic wall texture, we were able to gather evidence that TS presents with an intrinsic abnormality of the ascending aorta even in patients without concomitant BAV, CoA or dilatations as early as in childhood.
Assuntos
Anormalidades Múltiplas , Aorta/fisiopatologia , Valva Aórtica/diagnóstico por imagem , Síndrome de Turner/fisiopatologia , Malformações Vasculares/fisiopatologia , Rigidez Vascular/fisiologia , Adolescente , Aorta/anormalidades , Aorta/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Criança , Pré-Escolar , Ecocardiografia , Elasticidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Risco , Síndrome de Turner/complicações , Síndrome de Turner/diagnóstico , Malformações Vasculares/diagnóstico , Adulto JovemRESUMO
BACKGROUND: Although pediatric appropriate use criteria (AUC) for outpatient transthoracic echocardiography (TTE) are available, little is known about TTE utilization patterns before their release. The aims of this study were to determine the relation between AUC and TTE utilization and to identify patient and physician factors associated with discordance between the AUC and clinical practice. METHODS: A retrospective review of 3,000 initial outpatient pediatric cardiology encounters at six centers was performed. Investigator-determined indications were classified using AUC definitions. Concordance between AUC and TTE utilization was determined. Multivariate analysis was performed to identify patient and physician factors associated with TTE's being performed for rarely appropriate and TTE's not being performed for appropriate indications. RESULTS: Concordance between AUC and TTE utilization was 88%. TTE was performed for rarely appropriate indications in 9% and was associated with patient age < 3 months, indications of murmur, noninvasive imaging physician subspecialty, and physician volume. No TTE was ordered for appropriate indications in 3% and was associated with indications including prior test result (primarily abnormal electrocardiographic findings), older patients, and physician subspecialty other than generalist or imaging. There was high variability in TTE utilization among centers. CONCLUSIONS: There was a reasonable degree of concordance between AUC and clinical practice before AUC publication. Several patient and physician factors were associated with discordance with the AUC. These findings should be considered in efforts to disseminate the AUC and in the development of future iterations. The causes for variation among centers deserve further exploration.
Assuntos
Cardiologia , Ecocardiografia/estatística & dados numéricos , Fidelidade a Diretrizes , Cardiopatias/diagnóstico , Pacientes Ambulatoriais , Padrões de Prática Médica , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Whether a single nucleotide polymorphism (1601 G > A) in the factor VII-activating protease gene (FSAP Marburg I) is a risk factor for venous thromboembolism (VTE) is unclear. We investigated the relevance of the variant with respect to recurrentVTE. 854 patients with a first unprovoked VTE were followed for an average of 41 months after discontinuation of anticoagulation. Study endpoint was symptomatic recurrent VTE. VTE recurred in 7 of 41 patients (17%) with and in 106 of 813 patients (13%) without the variant. After 3 years, the probability of recurrence was 20.0% (95% CI, 5.3% to 34.6%) among patients with and 12.2% (95% CI, 9.6% to 14.8%) among those without FSAP Marburg I (p = 0.5). The relative recurrence risk among carriers of the variant was 1.3 (95% CI, 0.6 to 2.8; p = 0.5) before and 1.5 (95% CI, 0.7 to 3.3; p = 0.3) after adjustment for potentially confounding factors. We conclude that FSAP Marburg I is, if at all, only a mild factor for recurrent VTE. Patients with FSAP Marburg I most probably will not benefit from extended anticoagulation.
Assuntos
Serina Endopeptidases/genética , Tromboembolia/genética , Trombose Venosa/genética , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Recidiva , Fatores de Risco , Tromboembolia/prevenção & controle , Trombose Venosa/prevenção & controleRESUMO
OBJECTIVE: To compare two different expandable electrodes in radiofrequency ablation of renal cell carcinoma. METHODS: Percutaneous ablation was performed at two centers using either an expandable 7F umbrella-shaped LeVeen probe (diameter 2-4 cm) and a 200-W generator (group A), or an expandable Starburst XL electrode with a 150-W generator (group B). From each center, eight patients with one tumor each were matched retrospectively with regard to tumor volume, which was 9.71+/-6.43 cm3 for group A and 8.74+/-4.35 cm3 for group B (mean tumor diameter: 2.47+/-0.9 cm versus 2.50+/-0.4 cm, respectively). An unpaired t-test showed no significant difference in tumor volume between the two groups (p=0.820). RESULTS: Sixteen patients with 16 tumors were treated. The primary technical success of radiofrequency ablation was 94% (15 of 16 patients). After retreatment of residual tumor in one patient from group B, secondary technical success was 100%. No major complications were observed. The resulting mean volume of the almost spherical necroses was 21.1+/-9.1 cm3 versus 14.6+/-6.7 cm3 for groups A and B (diameter of necrosis: 3.5+/-0.7 cm versus 3.1+/-0.6 cm, respectively). A Mann-Whitney U-test showed no significant difference in necrosis volume between the two groups (CI [-0.215; 0.471]; p=0.2892). The calculated shape value of S (ratio of length to height of the coagulation necrosis) was 0.9+/-0.1 and 1.0+/-0.1 for groups A and B, respectively. No local recurrence was observed during a mean follow-up of 14.8+/-11.6 months, while extrarenal tumor progression occurred in three patients. CONCLUSIONS: No significant differences in coagulation volume and shape were found after RF ablation of renal cell carcinoma using two different expandable electrodes. To avoid local recurrence, however, accurate placement of probes and appropriate expansion of the electrode is necessary.
Assuntos
Carcinoma de Células Renais/cirurgia , Ablação por Cateter/instrumentação , Neoplasias Renais/cirurgia , Neoplasia Residual/cirurgia , Idoso , Carcinoma de Células Renais/patologia , Eletrodos/classificação , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: White matter hyperintensities (WMHs) on T(2)-weighted magnetic resonance imaging (MRI) of the brain are associated with advanced age and late-life depression. Most investigations predominantly found these lesions in frontal lobe and basal ganglia supporting the hypothesis of a fronto-striatal dysfunction in depression. A prospective study was undertaken to investigate the association between extent of WMHs and clinical outcome in elderly depressed patients. METHODS: Thirty-one non-demented depressed subjects underwent a 1.5 T cranial MRI scan. The MRI scans were analysed in consensus by two experienced radiologists. Each MRI scan was assessed for presence and extent of WMHs, which are differentiated in periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs). A total of 21 patients of the original cohort of 31 patients were re-assessed 5 years after baseline assessment. We ascertained the severity of depressive symptoms, the longitudinal course of depression, the cognitive decline and the global assessment of functioning at follow-up visit. RESULTS: (1) Subjects with greater extent of WMHs had a significant higher Hamilton Depression Rating Scale (HAM-D) score, (2) had more severe longitudinal courses of depression (3) and had a lower Mini-Mental State Examination (MMSE) score. CONCLUSIONS: WMHs on MRI are associated with poorer outcome in elderly depressed subjects. Further studies are needed to evaluate WHMs as prognostic factor for an appropriate treatment decision-making.
Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , Transtorno Depressivo Maior/patologia , Transtorno Depressivo Maior/fisiopatologia , Idoso , Gânglios da Base/patologia , Gânglios da Base/fisiopatologia , Ventrículos Cerebrais/patologia , Ventrículos Cerebrais/fisiopatologia , Doença Crônica , Corpo Estriado/patologia , Corpo Estriado/fisiopatologia , Tomada de Decisões , Feminino , Lobo Frontal/patologia , Lobo Frontal/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
Mice polytransgenic for chromosome 21 genes DSCR3, 5, 6, 9, and TTC3 within the Down Syndrome Critical Region-1 represent an animal model for Down Syndrome (DS). In a proteomic approach, we show a series of altered hippocampal protein levels that may be caused by overexpression of at least one of the five chromosome 21 genes and that fit fear-conditioned memory defects and were observed to be dysregulated in human fetal DS.
Assuntos
Cromossomos Humanos Par 21/genética , Síndrome de Down/metabolismo , Hipocampo/metabolismo , Proteoma/metabolismo , Animais , Síndrome de Down/genética , Regulação da Expressão Gênica , Hipocampo/química , Humanos , Camundongos , Camundongos Transgênicos , Biossíntese de Proteínas/genética , Proteínas/análise , Proteínas/genética , Proteínas/metabolismo , Proteoma/análise , Proteoma/genética , Proteômica , RNA Mensageiro/análise , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Vascular remodeling after percutaneous coronary stent implantation frequently leads to restenosis. Heme oxygenase 1 (HO-1) is involved in the generation of the endogenous antioxidant bilirubin and carbon monoxide, both of which exert antiinflammatory and antiproliferative effects. The aim of the present study was to evaluate the influence of genetic risk factors combined with the conventional risk factors on the development of coronary restenosis after percutaneous coronary intervention (PCI) with stent implantation. METHODS: The HO-1 gene GT dinucleotide repeat promoter polymorphism and HO-1 +99G/C variant were evaluated in 199 patients with coronary artery disease after coronary stent implantation and control angiography at 6 months after the intervention. Coronary restenosis was confirmed by quantitative angiography. RESULTS: Carriers of the long allele of the HO-1 gene promoter (>29 repeats) had a significantly higher risk of developing restenosis after PCI than noncarriers [odds ratio (OR)=1.9; 95% confidence interval (95% CI), 1.0-3.4; P=0.04]. Interestingly, the allele longer than 29 repeats conferred a significantly higher risk of developing restenosis (OR=3.4; 95% CI, 1.2-9.1; P=0.017) in nonsmokers than in smokers (OR=2.0; 95% CI, 0.7-5.2; P=0.18). CONCLUSIONS: The long allele of the HO-1 gene promoter (>29 repeats) polymorphism, which leads to low HO-1 inducibility, may represent an independent prognostic marker for restenosis after PCI and stent implantation. The effect of the >29 repeat allele is attenuated in smokers, who have chronic exogenous CO exposure.
Assuntos
Reestenose Coronária/genética , Heme Oxigenase (Desciclizante)/genética , Regiões Promotoras Genéticas , Stents/efeitos adversos , Idoso , Substituição de Aminoácidos , Angioplastia Coronária com Balão/efeitos adversos , Reestenose Coronária/etiologia , Estudos Transversais , Feminino , Genótipo , Heme Oxigenase-1 , Humanos , Isoenzimas/genética , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Polimorfismo Genético , Medição de Risco , Fumar/efeitos adversosRESUMO
OBJECTIVE: Familial hypercholesterolemia (FH) is a predominantly inherited disorder, which contributes to a defect of the LDL-cholesterol receptor. For adults with familial hypercholesterolemia (FH), it is known that a supplementary diet of monounsaturated fatty acids reduces elevated levels of total cholesterol and LDL-cholesterol and may further increase HDL-cholesterol. In particular the reduced intake of dietary fat reduces total serum cholesterol and LDL-cholesterol in the range of 10% to 15% and inhibits LDL-oxidation. Once the diagnosis of familial hypercholesterolemia is made in early childhood a supplementary diet with rapeseed oil should be started as early as possible to prevent development of atherosclerosis and subsequent complications. So far there are no reports of a lipid lowering diet enriched with rapeseed oil in children and adolescents. METHODS: Seventeen children and young adolescents (male = 6, female = 11, ages 4 to 19 years) diagnosed with FH were enrolled in this study. They received dietary training and a classical low fat/low cholesterol diet enriched with rapeseed oil over five months. In the first two months they received orally mean 15 g/day (8-23 g/day), for the remaining three months mean 22 g/day (15-30 g/day) rapeseed oil. The calculation of the three-days dietary protocols showed the following characteristics: 29.5% calories from fat, 14.3% calories from protein and 54.6% calories from carbohydrates. The subjects had six sessions of dietary counseling, and serum lipids levels and lipoprotein(a) were estimated; each month's diet adherence was controlled by a dietitian and discussed with the patients and their families during this five-month study. RESULTS: During five months of rapeseed oil diet serum triglycerides decreased by 29% (119.2+/-62.8 mg/dL vs. 84.9 mean +/- 39.7 mg/dL), VLDL-cholesterol by 27% (23+/-12 mg/dL vs. 17+/-8 mg/dL), total cholesterol by 10% (233+/-35 mg/dL vs. 213+/-36 mg/dL), LDL-cholesterol by 7% (151+/-31 mg/dL vs. 142+/-31 mg/dL). HDL-cholesterol (59+/-15 mg/dL vs. 57+/-11 mg/dL) and Lp(a) (29.8+/-36.3 mg/dL vs. 32.6+/-40.7 mg/dL) were not changed significantly. The diet was well accepted; in most families a sustained change was reported. CONCLUSIONS: Our results indicate that in children and adolescents with FH a lipid-lowering diet with rapeseed oil has a similar effect on total serum cholesterol and LDL-cholesterol compared to classical cholesterol reduction diets (step I). However, an additional pronounced effect on lowering of triglycerides and VLDL-cholesterol can be observed.
Assuntos
Gorduras Insaturadas na Dieta/administração & dosagem , Hiperlipoproteinemia Tipo II/dietoterapia , Lipídeos/sangue , Lipoproteínas/sangue , Óleos de Plantas/administração & dosagem , Adolescente , Índice de Massa Corporal , Criança , Pré-Escolar , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Ácidos Graxos Monoinsaturados , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Lipoproteína(a)/sangue , Masculino , Óleo de Brassica napus , Triglicerídeos/sangueRESUMO
Down syndrome (DS, trisomy 21) is the most frequent genetic cause of mental retardation. Although known for more than a hundred years the underlying pathomechanisms for the phenotype and impaired brain functions remain elusive. Performing protein hunting in fetal DS brain, we detected a series of cytoskeleton proteins with aberrant expression in fetal DS cortex. Fetal brain cortex samples of controls and DS of the early second trimenon of gestation were used for the experiments. We applied two-dimensional electrophoresis with in-gel digestion of protein spots, subsequent mass spectroscopical (MALDI) identification, and quantification of spots using specific software. Centractin alpha, F-actin capping protein alpha-1, alpha-2 and beta subunits were significantly reduced in fetal DS cortex, whereas dynein intermediate clear 2, dynein intermediate chain 2, and kinesin light chain protein levels were unchanged. Centractins and F-actin capping proteins are major determinants of the cytoskeleton and are involved in pivotal functions including cellular, organelle, and nuclear motility. Deranged centractins and F-actin capping proteins may represent or induce deficient axonal transport and may well contribute to deterioration of the cytoskeleton's mitotic functions in trisomy 21.
Assuntos
Actinas/metabolismo , Encéfalo/metabolismo , Síndrome de Down/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Fatores de Despolimerização de Actina , Actinas/análise , Encéfalo/embriologia , Encéfalo/patologia , Química Encefálica , Córtex Cerebral/química , Córtex Cerebral/embriologia , Córtex Cerebral/metabolismo , Destrina , Síndrome de Down/embriologia , Complexo Dinactina , Dineínas/análise , Dineínas/biossíntese , Eletroforese em Gel Bidimensional , Feminino , Feto , Humanos , Cinesinas/análise , Cinesinas/biossíntese , Masculino , Proteínas dos Microfilamentos/análise , Subunidades Proteicas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Major advances have been made in annotation of sequences of the human genome, although elucidating the functions of these newly discovered genes remains to be a strong challenge. In an effort to give insight into how triplication of chromosome 21 leads to mental retardation in Down syndrome, we have constructed a two-dimensional protein map from control and Down syndrome fetal brain and identified hypothetical proteins with no known functions. Subsequent quantitative analysis of these proteins revealed no apparent change in expression of hypothetical proteins DKZp564P0562.1 (fragment), 16.6, 21.4, 39.5, and 40kDa as well as putative 55kDa protein between controls and Down syndrome fetuses. By contrast, hypothetical protein 28.5kDa was significantly elevated (P<0.05) in fetal Down syndrome. This finding offers an important clue that a hypothetical protein might be involved in the pathomechanisms of brain abnormality in Down syndrome.
Assuntos
Encéfalo/embriologia , Síndrome de Down/metabolismo , Feto/metabolismo , Cromossomos Humanos Par 21/genética , Síndrome de Down/genética , Eletroforese em Gel Bidimensional , Feminino , Humanos , Masculino , Biossíntese de Proteínas , Estrutura Terciária de Proteína , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
The success of the Human Genome Project (HGP) enables prediction of proteins by computer programs from nucleic acid sequences and for which there is no experimental evidence. Clues for function of hypothetical proteins are provided by sequence similarity with proteins of known function in model organisms. The availability of this bulk of new data is of immediate importance to Down's syndrome (DS) research. DS is the most common human chromosomal abnormality caused by an extra copy of chromosome 21 and is characterized by somatic anomalies and mental retardation. In addition, overexpression of chromosome 21 genes is directly or indirectly responsible for mental retardation and other phenotypic abnormalities of DS. To allow insight into how trisomy 21 represents the phenotype of DS, we constructed a two-dimensional protein map and investigated expression of 8 hypothetical proteins in fetal DS (n = 7) and control (n = 7) brains (cortex). Two-dimensional electrophoresis (2-DE) with subsequent in-gel digestion of spots and matrix-assisted laser desorption/ionization (MALDI) spectroscopic identification followed by quantification of spots with specific software was applied. Quantitative analysis of hypothetical protein FLJ10849, hypothetical protein FLJ20113, and activator of hsp90 ATPase homologue 1 (AHA1) revealed levels comparable between DS and controls. By contrast, expression levels of hypothetical protein KIAA1185, hypothetical protein 55.2 kDa, hypothetical protein 58.8 kDa, actin-related protein 3beta (ARP3beta), and putative GTP-binding protein PTD004 were significantly decreased (P < 0.05) in fetal DS brain, and domain analysis suggests involvement in cytoskeleton, signaling, and chaperone system abnormalities.
Assuntos
Síndrome de Down/embriologia , Síndrome de Down/patologia , Proteínas do Tecido Nervoso/genética , Aborto Induzido , Aborto Espontâneo , Bases de Dados de Proteínas , Síndrome de Down/genética , Eletroforese em Gel Bidimensional , Feminino , Feto/patologia , Idade Gestacional , Humanos , Masculino , Proteínas do Tecido Nervoso/isolamento & purificação , Gravidez , Valores de Referência , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Although Down Syndrome (DS, trisomy 21) is the most frequent isolated cause of mental retardation, information on brain protein expression and in particular protein expression of signaling-related proteins is limited. Impaired signaling in DS involving different signaling systems has been proposed and the availability of fetal brain along with recent proteome technologies unambiguously identifying individual brain proteins made us study individual signaling factors in the brain. We studied fetal brain cortex of controls (n = 7) and DS (n = 9) from early second trimester of gestation by two-dimensional gel electrophoresis with subsequent matrix-assisted laser/desorption ionization (MALDI) identification followed by quantification with specific software. Four 14-3-3 protein isoforms, mitogen-activated protein kinase 1, receptor for activited kinase 1 (RACK1), constitutive photomorphogenesis (COP9) complex subunit 4 and cAMP-dependent protein kinase type II have been identified. Quantification showed that protein 14-3-3 gamma (means +/- standard deviation of controls: 10.18+/-2.30 and of DS 4.20+/-1.19) and two spots assigned to RACK1 (controls spot 1: 4.15+/-2.45 and DS 1.95+/-0.93; controls spot 2: 5.08+/-2.4 vs. DS: 2.56+/-1.19) were significantly decreased in DS cortex. Reduced 14-3-3 gamma may represent impaired neuronal differentiation, synaptic plasticity and impaired signaling by PKC and Raf while decreased RACK1 (anchoring protein receptor for activated C-kinase) may reflect or generate deranged beta-II- protein kinease C (PKC) function with the putative biological meaning of aberrant migration and neuritic outgrowth in DS early in life.