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1.
Tex Heart Inst J ; 51(1)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805371

RESUMO

BACKGROUND: Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown pathogenesis, frequently associated with neuromuscular disorders. The relevance of coronary artery disease (CAD) in LVHT is largely unknown. This study aimed to assess the role of CAD as a prognostic marker in LVHT. METHODS: Data from patients with LVHT were collected from an echocardiographic laboratory. The hospital information system was retrospectively screened for coronary angiography. The association of CAD with clinical, echocardiographic, and neurologic baseline parameters was assessed. End points were all-cause death and heart transplantation. RESULTS: A total of 154 patients (mean [SD] age, 57 [13.7] years; 31% female) who had undergone coronary angiography between 1995 and 2020 were included in the study. Coronary angiography disclosed CAD in 53 of 154 patients. Patients with CAD were older (mean [SD] age of, 64.2 [12.9] years vs 52.7 [12.4] years; P < .001); more frequently had angina pectoris (P = .05), diabetes (P = .002), and hypertension (P = .03); and more frequently had 3 or more electrocardiographic abnormalities (P = .04) than patients without CAD. During a median (IQR) follow-up period of 6.48 (2.44-11.20) years, 39% of patients reached an end point (death, n = 56; heart transplantation, n = 4). Mortality was 4.5% per year, and the rate of death or heart transplantation did not differ between patients with and without CAD (P = .26). Patients with 3-vessel disease had a worse prognosis than patients with 1- or 2-vessel disease (P = .046). CONCLUSION: In patients with LVHT, CAD does not appear to be associated with an increased rate of death or heart transplantation.


Assuntos
Angiografia Coronária , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Angiografia Coronária/métodos , Estudos Retrospectivos , Prognóstico , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/diagnóstico por imagem , Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Transplante de Coração , Idoso , Função Ventricular Esquerda/fisiologia , Seguimentos , Miocárdio Ventricular não Compactado Isolado/complicações , Miocárdio Ventricular não Compactado Isolado/diagnóstico , Miocárdio Ventricular não Compactado Isolado/mortalidade , Miocárdio Ventricular não Compactado Isolado/fisiopatologia
2.
J Med Case Rep ; 10(1): 281, 2016 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-27729057

RESUMO

BACKGROUND: Reversible left ventricular dysfunction, also termed Takotsubo cardiomyopathy, is rarely reported in Addison's disease after initiation of hormone replacement therapy. The pathogenesis of this cardiomyopathy is unknown. CASE PRESENTATION: A 41-year-old white woman with a history of autoimmune Hashimoto thyroiditis diagnosed 3 years earlier and acute adrenal insufficiency diagnosed 3 weeks earlier presented with new onset of heart failure New York Heart Association class IV, which had started shortly after initiation of hormone replacement therapy with hydrocortisone 20 mg/day and fludrocortisone 0.3 mg/day. Nine days before admission she had collapsed because of dizziness and had a cerebral concussion and open fracture of her nasal bone, however, no further investigations were carried out at that time. A physical examination revealed leg edema, tachycardia, tachypnea, bilateral basal crepitations, and blood pressure 110/70 mmHg. An electrocardiogram showed sinus tachycardia, low voltage, negative T-waves in V5 and V6 and a corrected QT interval of 590 ms. Echocardiography revealed a reduced left ventricular systolic function with an ejection fraction of 30 %, and septal, apical, and anterior wall akinesia. Cardiac magnetic resonance imaging showed relative enhancement of gadolinium, indicating hyperemia and capillary leakage, and no myocardial scars. Because of the improvement in her cardiac function, lack of cardiovascular risk factors, and lack of signs for ischemia on magnetic resonance imaging, no coronary angiography was carried out. The results of sellar and renal magnetic resonance imaging were normal. Her troponin T was slightly elevated. Bisoprolol and ramipril were started. Her fludrocortisone dose was reduced to 0.05 mg/day. Her electrocardiogram and systolic function, documented by echocardiography and magnetic resonance imaging, normalized within 6 months. CONCLUSIONS: Although we could not exclude coronary artery disease by coronary angiography, her clinical course and instrumental findings suggest Takotsubo cardiomyopathy of the apical type. Fludrocortisone overdosage and increased myocardial vulnerability due to cortisol deficiency might be pathogenetic factors, whereas myocarditis is unlikely. When hormone replacement in patients with Addison's disease is initiated, cardiac function should be monitored by electrocardiogram and echocardiography.


Assuntos
Doença de Addison/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Overdose de Drogas , Fludrocortisona/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Cardiomiopatia de Takotsubo/induzido quimicamente , Doença de Addison/fisiopatologia , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Biomarcadores , Bisoprolol/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Fludrocortisona/administração & dosagem , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Humanos , Ramipril/administração & dosagem , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/terapia , Resultado do Tratamento
3.
Int J Radiat Oncol Biol Phys ; 79(3): 866-74, 2011 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21183289

RESUMO

PURPOSE: To determine whether genetic variability in TGFB1 is related to circulating transforming growth factor-ß1 (TGF-ß1) plasma concentrations after radiotherapy and to radiosensitivity of lymphoid cells. PATIENTS AND METHODS: Transforming growth factor-ß1 plasma concentrations (n=79) were measured in patients 1 year after radiotherapy and chromosomal aberrations (n=71) ex vivo before therapy start. Furthermore, TGF-ß1 secretion and apoptosis were measured in isolated peripheral blood mononuclear cells of 55 healthy volunteers. These phenotypes were analyzed in relation to five germline polymorphisms in the 5' region of the TGFB1 gene. Because of high linkage disequilibrium, these five polymorphisms reflect frequent genetic variation in this region. A presumed impact of TGF-ß1 on DNA damage or repair was measured as micronucleus formation in 30 lymphoblastoid cell lines. RESULTS: We identified a hypofunctional genetic haplotype termed H3 tagging the 5' region of the TGFB1 gene encoding TGF-ß1. H3 was associated with lower TGF-ß1 plasma concentrations in patients (p=0.01) and reduced TGF-ß1 secretion in irradiated peripheral blood mononuclear cells (p=0.003). Furthermore, cells with H3 were less prone to induction of chromosomal aberrations (p=0.001) and apoptosis (p=0.003) by irradiation. The hypothesis that high TGF-ß1 could sensitize cells to DNA damage was further supported by increased micronuclei formation in 30 lymphoblastoid cell lines when preincubated with TGF-ß1 before irradiation (p=0.04). CONCLUSIONS: On the basis of TGF-ß1 plasma levels and radiation sensitivity of lymphoid cells, this study revealed a putatively hypofunctional TGFB1 haplotype. The significance of this haplotype and the suggested link between TGF-ß1 function and DNA integrity should be further explored in other cell types, as well as other experimental and clinical conditions.


Assuntos
Haplótipos/genética , Tolerância a Radiação/genética , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores/sangue , Linhagem Celular , Dano ao DNA , Feminino , Haplótipos/fisiologia , Humanos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/fisiologia , Leucócitos Mononucleares/efeitos da radiação , Desequilíbrio de Ligação , Masculino , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
4.
Pharmacogenet Genomics ; 19(4): 249-59, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19214138

RESUMO

OBJECTIVES: The transforming growth factor-beta (TGFB) pathway has substantial impact on cellular functions, cell proliferation, and apoptosis. We used bioinformatics, gene expression, and cell biological assays to evaluate the functionality of frequent inherited germline polymorphisms in the TGFB receptor 1 (TGFBR1). METHODS: In an exploratory (n=55) and confirmatory (n=106) study, we analyzed the TGFB1 pathway after incubation with TGFbeta1 ligand and after exposure to X-rays in peripheral blood human mononuclear cells. Expression of TGFB pathway genes was assessed by real-time PCR, and cellular viability was analyzed by flow cytometry. A total of six polymorphisms including the deletion variant (*6A) were identified to tag currently known common genetic variations in TGFBR1 and were analyzed in relation to the phenotypes. RESULTS: In accordance with a negative feedback mechanism, incubations with the ligand TGFbeta1 was followed by up-regulation of the intracellular SMAD7 and down-regulation of the SMAD3 mRNA molecules. The TGFBR1*6A deletion variant attenuated the suppression of SMAD3 in response to TGFbeta1 (P=0.02, in both studies). Moreover, cells harboring *6A were more sensitive toward cytotoxic effects of irradiation (P=0.001 after adjustment for age and sex). Cells were particularly prone toward radiation toxicity when carrying, in addition to *6A, the variant allele of rs11568785, which exhibits a strong genetic selection signature. CONCLUSION: The *6A deletion and the linked rs11568785 polymorphisms seem to attenuate TGFB signaling. This should be considered not only for clinical-epidemiological studies on cancer susceptibility but may also be relevant for side effects from drugs or radiotherapy.


Assuntos
Biologia Computacional/métodos , Polimorfismo Genético , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais , Adulto , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Variação Genética , Haplótipos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/efeitos da radiação , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/farmacologia , RNA Mensageiro/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I , Proteínas Recombinantes/metabolismo , Transdução de Sinais/genética , Raios X , Adulto Jovem
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