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1.
Echocardiography ; 29(9): 1022-30, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22758401

RESUMO

BACKGROUND: Cardiovascular risk stratification in Turner syndrome (TS) is difficult. Increased left ventricular mass associates with an adverse prognosis in several settings, and this study aimed to elucidate this risk marker in relation to metabolic and cardiovascular status in TS. METHODS: An echocardiographic follow-up study (4.8 years) of 82 adult females with TS. Left ventricular mass was the primary outcome parameter. Metabolic status (glucose, Hemoglobin A1c, lipids), aortic valve function and morphology, and 24-hour ambulatory blood pressure were secondary outcome parameters. Healthy age-matched females served as baseline controls (n = 55). RESULTS: Left ventricular mass was increased in TS (TS vs. controls: 88 ± 21 g/m(2) vs. 77 ± 12 g/m(2), P < 0.05). More participants were treated for hypertension at follow-up (32% at baseline vs. 55% at follow-up). This coincided with a reduction of left ventricular mass in TS (84 ± 20 g/m(2) at follow up, P < 0.05) and favorable remodeling with a contrasting increase in left atrial size. In a baseline multiple regression model, left ventricular mass (r(2) = 0.28, P < 0.05) increased with body surface area, age and the presence of a bicuspid aortic valve. In another model, left ventricular mass increased with blood pressure, ongoing estrogen treatment and body surface area (r(2) = 0.26, P < 0.05). No single factor reached statistically significant levels for prediction of prospective left ventricular mass changes. CONCLUSION: The increased left ventricular mass in TS was associated with aortic valve disease, age, hypertension, physical stature and metabolic status. During follow-up left ventricular mass was only slightly reduced along with blood pressure, whereas the diastolic dysfunction did not seem to improve.


Assuntos
Ecocardiografia/estatística & dados numéricos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Síndrome de Turner/diagnóstico por imagem , Síndrome de Turner/epidemiologia , Adulto , Idoso , Comorbidade , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e Especificidade , Adulto Jovem
2.
Cardiol Young ; 20(2): 191-200, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20307329

RESUMO

BACKGROUND: Ectatic aortopathy and arterial abnormalities cause excess morbidity and mortality in Turner syndrome, where a state of vasculopathy seemingly extends into the major head and neck branch arteries. OBJECTIVE: We investigated the prevalence of abnormalities of the major intrathoracic arteries, their interaction with arterial dimensions, and their association with karyotype. DESIGN: Magnetic resonance imaging scans determined the arterial abnormalities as well as head and neck branch artery and aortic dimensions in 99 adult women with Turner syndrome compared with 33 healthy female controls. Echocardiography determined aortic valve morphology. RESULTS: In Turner syndrome, the relative risk of any congenital abnormality was 7.7 (p = 0.003) and 6.7 of ascending aortic dilation (p = 0.02). A bovine aortic arch was seen in both Turner syndrome and controls. Other abnormalities were only encountered in Turner syndrome: elongated transverse aortic arch (47%), bicuspid aortic valve (27%), aortic coarctation (13%), aberrant right subclavian artery (8%), and aortic arch hypoplasia (2%). The innominate and left common carotid arteries were enlarged in Turner syndrome (p < 0.001). Significant associations were first, bicuspid aortic valve with aortic coarctation, elongated transverse aortic arch, and ascending aortic dilation; second, aortic coarctation with elongated aortic arch and descending aortic dilation; third, 45,X with aortic coarctation, elongated transverse aortic arch and ascending aortic dilation; and fourth, branch artery dilation with bicuspid aortic valve, aortic coarctation, elongated transverse aortic arch and 45,X. CONCLUSION: An increased risk of arterial abnormalities, aortic dilation, and enlargement of the branch arteries was found in Turner syndrome without distinct patterns of co-segregation.


Assuntos
Tronco Braquiocefálico/patologia , Artéria Carótida Primitiva/patologia , Artéria Subclávia/patologia , Síndrome de Turner/patologia , Adolescente , Adulto , Aorta Torácica/patologia , Tronco Braquiocefálico/diagnóstico por imagem , Artéria Carótida Primitiva/diagnóstico por imagem , Dilatação Patológica , Feminino , Cabeça/irrigação sanguínea , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Pescoço/irrigação sanguínea , Artéria Subclávia/diagnóstico por imagem , Síndrome de Turner/diagnóstico por imagem , Ultrassonografia , Adulto Jovem
3.
Eur J Endocrinol ; 155(4): 583-92, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16990658

RESUMO

BACKGROUND: Body composition in Turner syndrome (TS) is altered with final height of TS decreased; anthropometry and bone mass distinctly changed. AIM: To describe total and regional distribution of fat and muscle mass in TS and the relation to measures of glucose metabolism, sex hormones, IGFs, and markers of inflammation and vascular function. MATERIAL AND METHODS: Fifty-four women with TS (mean age, 42.5 +/- 9.7 years) and an age-matched group of controls (n = 55) were examined by dual-energy X-ray absorptiometry scans with determination of regional body composition and estimation of visceral fat and skeletal muscle mass. We determined maximal oxygen uptake and assessed physical activity using a questionnaire. We measured serum adiponectin, ghrelin, IGF-I, IGF-binding protein-3 (IGFBP-3), estradiol, testosterone, sex hormone-binding globulin (SHBG), insulin, glucose, cytokines, vascular cell adhesion molecule-I, and intercellular cell adhesion molecule-I. Insulin sensitivity was estimated. Multiple linear regression models were used to examine the relationships between variables. RESULTS: TS had lower total lean body mass (LBM), while body mass index (BMI) and total fat mass (FM) were increased. We found increased visceral FM, and decreased trunk LBM, appendicular LBM, and skeletal muscle mass. VO2max and physical activity were significantly lower in TS, as were most hormone levels, except increased leptin. In multiple linear regression models, status (i.e. TS or control) was a consistent contributing variable. CONCLUSION: Profound changes are present in body composition in TS, with increased FM, and decreased skeletal muscle mass. Circulating hormones, VO2max, and insulin sensitivity influence body composition. The accumulation of visceral fat would predict a higher risk of development of the insulin resistance syndrome.


Assuntos
Composição Corporal , Moléculas de Adesão Celular/sangue , Citocinas/sangue , Glucose/metabolismo , Síndrome de Turner/sangue , Síndrome de Turner/complicações , Adipócitos/metabolismo , Adulto , Idoso , Antropometria , Biomarcadores/sangue , Glicemia/análise , Metabolismo dos Carboidratos , Moléculas de Adesão Celular/metabolismo , Citocinas/metabolismo , Células Endoteliais/metabolismo , Feminino , Hormônios Esteroides Gonadais/sangue , Homeostase , Humanos , Resistência à Insulina , Molécula 1 de Adesão Intercelular/sangue , Cariotipagem , Pessoa de Meia-Idade , Atividade Motora , Somatomedinas/análise , Molécula 1 de Adesão de Célula Vascular/sangue
4.
Eur J Endocrinol ; 167(4): 543-51, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22872467

RESUMO

CONTEXT: Estradiol (E(2)) promotes and maintains the female phenotype characterized by subcutaneous fat accumulation. There is evidence to suggest that this effect is due to increased anti-lipolytic α2A-adrenergic receptors, but whether this requires long-term exposure to E(2) or is an immediate effect is not clear. OBJECTIVE: To study acute effects of a single dose (4 mg) of 17ß-E(2) on regional and systemic lipolysis. METHODS: Sixteen postmenopausal women (age, 595 years; weight, 6710 kg; and BMI, 24.82.9) were studied in a crossover design: i) placebo and ii) 4 mg E(2). Basal and adrenaline-stimulated regional lipolysis was assessed by microdialysis and substrate oxidation rates by indirect calorimetry. Tissue biopsies were obtained to assess lipoprotein lipase activity and mRNA expression of adrenergic, estrogen, cytokine, and vascular reactivity receptors. RESULTS: Acute E(2) stimulation significantly attenuated catecholamine-stimulated lipolysis in femoral subcutaneous adipose tissue (interstitial glycerol concentration (micromole/liter) ANOVA time vs treatment interaction, P=0.01) and lipolysis in general in abdominal adipose tissue (ANOVA treatment alone, P<0.05). E(2) also reduced basal lipid oxidation ((mg/kg per min) placebo, 0.58 ± 0.06 vs E(2), 0.45 ± 0.03; P=0.03) and induced a significantly higher expression of anti-lipolytic α2A-adrenergic receptor mRNA (P=0.02) in skeletal muscle tissue as well as an upregulation of eNOS (NOS3) mRNA (P=0.02). CONCLUSION: E(2) acutely attenuates the lipolytic response to catecholamines in subcutaneous adipose tissue, shifts muscular adrenergic receptor mRNA toward anti-lipolytic α2A-receptors, decreases whole body lipid oxidation, and enhances expression of markers of vascular reactivity.


Assuntos
Estradiol/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Pós-Menopausa/efeitos dos fármacos , Gordura Subcutânea/efeitos dos fármacos , Estudos Cross-Over , Regulação para Baixo/efeitos dos fármacos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Oxirredução/efeitos dos fármacos , Placebos , Pós-Menopausa/metabolismo , Método Simples-Cego , Gordura Subcutânea/metabolismo , Fatores de Tempo
5.
Eur J Endocrinol ; 163(3): 421-6, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20566588

RESUMO

CONTEXT: Long-term hormone replacement therapy (HRT) with estradiol (E(2)) is associated with an altered lipid profile including unfavorable increases in triglyceride (TG) concentrations and augmented hepatic very low-density lipoprotein (VLDL)-TG production. There are indications that this effect of estrogens may be immediate. OBJECTIVE: To study the in vivo effect of a single dose of E(2) on VLDL-TG kinetics and oxidation in humans. METHODS: Eight healthy, postmenopausal women were given a single dose of either placebo or E(2) (4 mg) orally. VLDL-TG kinetics was assessed by a 240-min primed-continuous infusion of ex vivo labeled [1-(14)C]triolein-labeled VLDL. Fractional and absolute VLDL-TG oxidation was determined by hyamin trapping of exhaled (14)C label. Indirect calorimetry provided measurements of lipid oxidation. RESULTS: Administration of 4 mg of E(2) orally rapidly increased plasma E(2) concentrations from below detection threshold to premenopausal levels. Free fatty acids (FFA) and TG concentrations were unaltered. No immediate effect was observed on either VLDL-TG production (placebo versus E(2)): 20.0+/-12.4 vs 24.1+/-10.7 micromol/min, P=0.33; VLDL-TG oxidation: 12.3+/-10.9 vs 12.6+/-5.6 micromol/min, P=0.93); or VLDL-TG clearance rates: 51.4+/-16.8 vs 64.9+/-28.8 ml/min, P=0.34). CONCLUSIONS: Short-term E(2) elevation does not affect VLDL-TG production, oxidation, or clearance in humans. We therefore propose that HRT-associated dyslipidemia has a gradual rather than immediate onset.


Assuntos
Estradiol/administração & dosagem , Lipoproteínas VLDL/sangue , Pós-Menopausa/sangue , Pós-Menopausa/efeitos dos fármacos , Triglicerídeos/sangue , Estrogênios/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Oxirredução/efeitos dos fármacos , Fatores de Tempo
6.
Cardiol Young ; 16(5): 430-6, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16984695

RESUMO

BACKGROUND: Women with Turner's syndrome have an increased risk of congenital cardiac malformations, ischaemic heart disease, hypertension and stroke. Aortic dissection seems to occur with increased frequency. AIM: To describe in more detail aortic dissection as encountered in Turner's syndrome, giving attention to clinical, histological and epidemiological aspects. MATERIALS AND METHODS: Based on a retrospective study, we describe the clinical, karyotypic, and epidemiological aspects of aortic dissection as encountered in cases of Turner's syndrome seen in Denmark and Sweden. RESULTS: The median age at onset of aortic dissection in 18 women was 35 years, ranging from 18 to 61 years. Fourteen of 18 women had a 45,X karyotype, while 2 patients had 45,X/45,XY, and 2 had the 45,X/46,X+r(X) complement, respectively. Echocardiography was performed in 10 of 18 patients before their acute illness, and showed signs of congenital cardiac disease, with either bifoliate aortic valves, dilation of the aortic root, or previous aortic coarctation evident in most patients. In 5 patients evidence of a bifoliate aortic valve was conclusive. Hypertension was present in 5 of 18 patients, while 10 of the patients died from aortic dissection, of so-called type A in 6, type B in 3, while in the final case the origin of dissection could not be determined. Biochemical analysis showed altered ratio between type I and type III collagen. Histology showed cystic medial necrosis in 3 of 7 cases. We estimated an incidence of dissection of 36 per 100,000 Turner's syndrome years, compared with an incidence of 6 per 100,000 in the general population, and a cumulated rate of incidence of 14, 73, 78, and 50 per 100,000 among 0-19, 20-29, 30-39, and 40+ year olds, respectively. CONCLUSION: Aortic dissection is extremely common in the setting of Turner's syndrome, and occurs early in life. Patients with Turner's syndrome should be offered a protocol for clinical follow-up similar to that provided for patients with Marfan syndrome, and each clinic should embrace a programme for follow-up.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Síndrome de Turner , Adolescente , Adulto , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/epidemiologia , Dissecção Aórtica/etiologia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/epidemiologia , Aneurisma da Aorta Torácica/etiologia , Biópsia , Dinamarca/epidemiologia , Diagnóstico Diferencial , Ecocardiografia , Feminino , Seguimentos , Humanos , Incidência , Cariotipagem , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Síndrome de Turner/complicações , Síndrome de Turner/diagnóstico , Síndrome de Turner/genética
7.
Clin Endocrinol (Oxf) ; 62(5): 616-22, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15853835

RESUMO

OBJECTIVE: Girls with Turner syndrome (TS) receive GH treatment during childhood, and in adolescence this treatment may be combined with oestradiol. We have studied the effects of this combined treatment on metabolism and body composition. MATERIAL AND METHODS: We performed a double-blind, placebo-controlled, randomized, crossover study. All girls with TS (n = 8, 16 +/- 2 years) were treated with placebo + placebo, GH + placebo or GH + 17beta-oestradiol for 2 months, and were studied at the end of each period. Controls (n = 10, 14 +/- 2 years) were studied once without treatment. Twenty-four-hour sampling of oestradiol, growth factors, insulin, glucose, lipolytic and gluconeogenic precursors was performed, followed by an oral glucose tolerance test (OGTT) and assessment of body composition and mineral content. RESULTS: GH induced insulin resistance, which was not aggravated further by concomitant oestradiol treatment. The 24-h integrated serum 17beta-oestradiol was reduced compared to controls (0.58 +/- 0.32 vs. 2.81 +/- 2.78 nmol/l/24 h, P = 0.032), but increased during GH + oestrogen (E2) treatment without reaching control levels, while GH + placebo caused a further reduction (anova, P = 0.008). Total fat mass was increased in girls with TS compared with controls (P = 0.009), while lean body mass (P = 0.02) and bone mineral content (P = 0.04) was decreased, with specific regional characteristics in body composition. CONCLUSION: GH treatment induces insulin resistance and changes in body composition in TS, which is not further compromised by concomitant oestradiol treatment. Body composition is changed in TS, with specific regional changes, in comparison with controls. Integrated 24-h oestradiol is low in TS, and is only partially restored during treatment with standard doses of 17beta-oestradiol.


Assuntos
Estradiol/uso terapêutico , Hormônio do Crescimento/uso terapêutico , Síndrome de Turner/tratamento farmacológico , Adolescente , Glicemia/análise , Composição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Estudos de Casos e Controles , Estudos Cross-Over , Método Duplo-Cego , Quimioterapia Combinada , Estradiol/sangue , Feminino , Glucagon/sangue , Teste de Tolerância a Glucose , Hormônio do Crescimento/sangue , Humanos , Insulina/sangue , Resistência à Insulina , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Lipídeos/sangue , Síndrome de Turner/sangue , Síndrome de Turner/fisiopatologia
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