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1.
J Am Coll Cardiol ; 75(10): 1111-1124, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32164884

RESUMO

BACKGROUND: Until now, high-sensitivity cardiac troponin (hs-cTn) assays were mainly developed for large central laboratory platforms. OBJECTIVES: This study aimed to assess the clinical performance of a point-of-care (POC)-hs-cTnI assay in patients with suspected myocardial infarction (MI). METHODS: This study enrolled patients presenting to the emergency department with symptoms suggestive of MI. Two cardiologists centrally adjudicated the final diagnosis using all clinical data including cardiac imaging. The primary objective was to directly compare diagnostic accuracy of POC-hs-cTnI-TriageTrue versus best-validated central laboratory assays. Secondary objectives included the derivation and validation of a POC-hs-cTnI-TriageTrue-specific 0/1-h algorithm. RESULTS: MI was the adjudicated final diagnosis in 178 of 1,261 patients (14%). The area under the curve (AUC) for POC-hs-cTnI-TriageTrue at presentation was 0.95 (95% confidence interval [CI]: 0.93 to 0.96) and was at least comparable to hs-cTnT-Elecsys (AUC: 0.94; 95% CI: 0.93 to 0.96; p = 0.213) and hs-cTnI-Architect (AUC: 0.92; 95% CI: 0.90 to 0.93; p < 0.001). A single cutoff concentration <3 ng/l at presentation identified 45% of patients at low risk with a negative predictive value (NPV) of 100% (95% CI: 99.4% to 100%). A single cutoff concentration >60 ng/l identified patients at high risk with a positive predictive value (PPV) of 76.8% (95% CI: 68.9% to 83.6%). The 0/1-h algorithm ruled out 55% of patients (NPV: 100%; 95% CI: 98.8% to 100%), and ruled in 18% of patients (PPV: 76.8%; 95% CI: 67.2% to 84.7%). Ruled-out patients had cumulative event rates of 0% at 30 days and 1.6% at 2 years. This study confirmed these findings in a secondary analysis including hs-cTnI-Architect for central adjudication. CONCLUSIONS: The POC-hs-cTnI-TriageTrue assay provides high diagnostic accuracy in patients with suspected MI with a clinical performance that is at least comparable to that of best-validated central laboratory assays. (Advantageous Predictors of Acute Coronary Syndromes Evaluation Study [APACE]; NCT00470587).

2.
Clin Chem ; 65(11): 1426-1436, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31570633

RESUMO

BACKGROUND: We aimed to validate the clinical performance of the high-sensitivity cardiac troponin I [VITROS® Immunodiagnostic Products hs Troponin I (hs-cTnI-VITROS)] assay. METHODS: We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists considering all clinical information, including cardiac imaging: first, using serial hs-cTnT-Elecsys (primary analysis) and, second, using hs-cTnI-Architect (secondary analysis) measurements in addition to the clinically used (hs)-cTn. hs-cTnI-VITROS was measured at presentation and at 1 h in a blinded fashion. The primary objective was direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI-VITROS vs hs-cTnT-Elecsys and hs-cTnI-Architect, and in a subgroup also hs-cTnI-Centaur and hs-cTnI-Access. Secondary objectives included the derivation and validation of an hs-cTnI-VITROS-0/1-h algorithm. RESULTS: AMI was the adjudicated final diagnosis in 158 of 1231 (13%) patients. At presentation, the AUC for hs-cTnI-VITROS was 0.95 (95% CI, 0.93-0.96); for hs-cTnT-Elecsys, 0.94 (95% CI, 0.92-0.95); and for hs-cTnI-Architect, 0.92 (95% CI, 0.90-0.94). AUCs for hs-cTnI-Centaur and hs-cTnI-Access were 0.95 (95% CI, 0.94-0.97). Applying the derived hs-cTnI-VITROS-0/1-h algorithm (derivation cohort n = 519) to the validation cohort (n = 520), 53% of patients were ruled out [sensitivity, 100% (95% CI, 94.1-100)] and 14% of patients were ruled in [specificity, 95.6% (95% CI, 93.4-97.2)]. Patients ruled out by the 0/1-h algorithm had a survival rate of 99.8% at 30 days. Findings were confirmed in the secondary analyses using the adjudication including serial measurements of hs-cTnI-Architect. CONCLUSIONS: The hs-cTnI-VITROS assay has at least comparable diagnostic accuracy with the currently best validated hs-cTnT and hs-cTnI assays. CLINICALTRIALSGOV IDENTIFIER: NCT00470587.

3.
J Am Coll Cardiol ; 74(7): 842-854, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31416527

RESUMO

BACKGROUND: Early and accurate detection of short-term major adverse cardiac events (MACE) in patients with suspected acute myocardial infarction (AMI) is an unmet clinical need. OBJECTIVES: The goal of this study was to test the hypothesis that adding clinical judgment and electrocardiogram findings to the European Society of Cardiology (ESC) high-sensitivity cardiac troponin (hs-cTn) measurement at presentation and after 1 h (ESC hs-cTn 0/1 h algorithm) would further improve its performance to predict MACE. METHODS: Patients presenting to an emergency department with suspected AMI were enrolled in a prospective, multicenter diagnostic study. The primary endpoint was MACE, including all-cause death, cardiac arrest, AMI, cardiogenic shock, sustained ventricular arrhythmia, and high-grade atrioventricular block within 30 days including index events. The secondary endpoint was MACE + unstable angina (UA) receiving early (≤24 h) revascularization. RESULTS: Among 3,123 patients, the ESC hs-cTnT 0/1 h algorithm triaged significantly more patients toward rule-out compared with the extended algorithm (60%; 95% CI: 59% to 62% vs. 45%; 95% CI: 43% to 46%; p < 0.001), while maintaining similar 30-day MACE rates (0.6%; 95% CI: 0.3% to 1.1% vs. 0.4%; 95% CI: 0.1% to 0.9%; p = 0.429), resulting in a similar negative predictive value (99.4%; 95% CI: 98.9% to 99.6% vs. 99.6%; 95% CI: 99.2% to 99.8%; p = 0.097). The ESC hs-cTnT 0/1 h algorithm ruled-in fewer patients (16%; 95% CI: 14.9% to 17.5% vs. 26%; 95% CI: 24.2% to 27.2%; p < 0.001) compared with the extended algorithm, albeit with a higher positive predictive value (76.6%; 95% CI: 72.8% to 80.1% vs. 59%; 95% CI: 55.5% to 62.3%; p < 0.001). For 30-day MACE + UA, the ESC hs-cTnT 0/1 h algorithm had a higher positive predictive value for rule-in, whereas the extended algorithm had a higher negative predictive value for the rule-out. Similar findings emerged when using hs-cTnI. CONCLUSIONS: The ESC hs-cTn 0/1 h algorithm better balanced efficacy and safety in the prediction of MACE, whereas the extended algorithm is the preferred option for the rule-out of 30-day MACE + UA. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587).


Assuntos
Algoritmos , Infarto do Miocárdio/epidemiologia , Troponina/sangue , Idoso , Angina Instável/diagnóstico , Angina Instável/epidemiologia , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Bloqueio Atrioventricular/diagnóstico , Bloqueio Atrioventricular/epidemiologia , Biomarcadores/sangue , Eletrocardiografia , Serviço Hospitalar de Emergência , Feminino , Parada Cardíaca/diagnóstico , Parada Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Revascularização Miocárdica , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/epidemiologia
4.
Clin Chem ; 65(7): 893-904, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30988172

RESUMO

BACKGROUND: The aim of this study was to validate the clinical performance of the Beckman Access high-sensitivity cardiac troponin I (hs-cTnI) assay. METHODS: We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists with all clinical information including cardiac imaging twice: first, using serial hs-cTnT (Elecsys, primary analysis), and second, using hs-cTnI (Architect, secondary analysis) measurements in addition to the clinically used hs-cTn. hs-cTnI Access was measured at presentation and at 1 h. The primary objective was a direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI Access vs the hs-cTnT Elecsys and hs-cTnI Architect assays. Secondary objectives included the derivation and validation of an hs-cTnI Access-specific 0/1-h algorithm. RESULTS: AMI was the adjudicated final diagnosis in 243 of 1579 (15.4%) patients. The AUC at presentation for hs-cTnI Access was 0.95 (95% CI, 0.94-0.96), higher than hs-cTnI Architect [0.92 (95% CI, 0.91-0.94; P < 0.001)] and comparable to hs-cTnT Elecsys [0.94 (95% CI, 0.93-0.95; P = 0.12)]. Applying the derived hs-cTnI Access 0/1-h algorithm (derivation cohort n = 686) to the validation cohort (n = 680), 60% of patients were ruled out [sensitivity, 98.9% (95% CI, 94.3-99.8)], and 15% of patients were ruled in [specificity, 95.9% (95% CI, 94.0-97.2)]. Patients ruled out by the 0/1-h algorithm had a survival rate of 100% at 30 days. Findings were confirmed in the secondary analyses by the adjudication including serial measurements of Architect hs-cTnI. CONCLUSIONS: Diagnostic accuracy and clinical utility of the Beckman hs-cTnI Access assay are very high and at least comparable to Roche hs-cTnT and Abbott hs-cTnI assays. ClinicalTrials.gov Identifier: NCT00470587.


Assuntos
Infarto do Miocárdio/diagnóstico , Troponina I/sangue , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Área Sob a Curva , Biomarcadores/sangue , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Estudos Prospectivos , Curva ROC , Troponina T/sangue
5.
Clin Chem ; 65(3): 437-450, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30626633

RESUMO

BACKGROUND: We desired to determine cardiac troponin (cTn) concentrations necessary to achieve a positive predictive value (PPV) of ≥75% for acute myocardial infarction (AMI) to justify immediate admission of patients to a monitored unit and, in general, early coronary angiography. METHODS: In a prospective multicenter diagnostic study enrolling patients presenting to the emergency department with symptoms suggestive of AMI, final diagnoses were adjudicated by 2 independent cardiologists based on clinical information including cardiac imaging. cTn concentrations were measured using 5 different sensitive and high-sensitivity cTn (hs-cTn) assays in a blinded fashion at presentation and serially thereafter. The diagnostic end point was PPV for rule-in of AMI of initial cTn concentrations alone and in combination with early changes. RESULTS: Among 3828 patients, 616 (16%) had an AMI. At presentation, 7% to 14% of patients had cTnT/I concentrations associated with a PPV of ≥75%. Adding absolute or relative changes did not significantly further increase the PPV. PPVs increased from 46.5% (95% CI, 43.6-49.4) for hs-cTnT at presentation >14 ng/L to 78.9% (95% CI, 74.7-82.5) for >52 ng/L (P < 0.001), whereas PPVs in higher hs-cTnT strata remained largely unchanged [e.g., 82.4% (95% CI, 77.5-86.7) for >80 ng/L vs 83.9% (95% CI, 76.0-90.1) for >200 ng/L (P = 0.72)]. The addition of early changes in hs-cTnT further increased the PPV up to 60 ng/L, but not for higher concentrations. CONCLUSIONS: Serial sampling does not seem necessary for predicting AMI and concurrent decision-making in about 10% of patients, as it only marginally increases the PPV for AMI and not in a statistically or clinically significant way. CLINICALTRIALSGOV IDENTIFIER: NCT00470587.


Assuntos
Infarto do Miocárdio/diagnóstico , Troponina I/sangue , Troponina T/sangue , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Análise Química do Sangue/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos
6.
Eur Heart J ; 39(42): 3780-3794, 2018 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-30169752

RESUMO

Aims: We aimed to evaluate the impact of age on the performance of the European Society of Cardiology (ESC) 0/1h-algorithms and to derive and externally validate alternative cut-offs specific to older patients. Methods and results: We prospectively enrolled patients presenting to the emergency department (ED) with symptoms suggestive of acute myocardial infarction in three large diagnostic studies. Final diagnoses were adjudicated by two independent cardiologists. High-sensitivity cardiac troponin (hs-cTn) T and I concentrations were measured at presentation and after 1 h. Patients were stratified according to age [<55 years (young), ≥55 to <70 years (middle-age), ≥70 years (old)]. Rule-out safety of the ESC hs-cTnT 0/1h-algorithm was very high in all age-strata: sensitivity 100% [95% confidence interval (95% CI) 94.9-100] in young, 99.3% (95% CI 96.0-99.9) in middle-age, and 99.3% (95% CI 97.5-99.8) in old patients. Accuracy of rule-in decreased with age: specificity 97.0% (95% CI 95.8-97.9) in young, 96.1% (95% CI 94.5-97.2) in middle-age, and 92.7% (95% CI 90.7-94.3) in older patients. Triage efficacy decreased with increasing age (young 93%, middle-age 80%, old 55%, P < 0.001). Similar results were found for the ESC hs-cTnT 0/1h-algorithm. Alternative, slightly higher cut-off concentrations optimized for older patients maintained very high safety of rule-out, increased specificity of rule-in (P < 0.01), reduced overall efficacy for hs-cTnT (P < 0.01), while maintaining efficacy for hs-cTnI. Findings were confirmed in two validation cohorts (n = 2767). Conclusion: While safety of the ESC 0/1h-algorithms remained very high, increasing age significantly reduced overall efficacy and the accuracy of rule-in. Alternative slightly higher cut-off concentrations may be considered for older patients, particularly if using hs-cTnI. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00470587, number NCT00470587 and NCT02355457 (BACC).


Assuntos
Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Adulto , Fatores Etários , Idoso , Algoritmos , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Sensibilidade e Especificidade , Troponina/sangue
8.
Crit Rev Clin Lab Sci ; 54(2): 102-116, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28102101

RESUMO

Thyroid hormones are crucial for the growth and maturation of many target tissues, especially the brain and skeleton. During critical periods in the first trimester of pregnancy, maternal thyroxine is essential for fetal development as it supplies thyroid hormone-dependent tissues. The ontogeny of mature thyroid function involves organogenesis, and maturation of the hypothalamus, pituitary and the thyroid gland; and it is almost complete by the 12th-14th gestational week. In case of maternal hypothyroidism, substitution with levothyroxine must be started in early pregnancy. After the 14th gestational week, fetal brain development may already be irreversibly affected by lack of thyroid hormones. The prevalence of manifest hypothyroidism in pregnancy is about 0.3-0.5%. The prevalence of subclinical hypothyroidism varies between 4 and 17%, strongly depending on the definition of the upper TSH cutoff limit. Hyperthyroidism occurs in 0.1-1% of all pregnancies. Positivity for antibodies against thyroid peroxidase (TPOAb) is common in women of childbearing age with an incidence rate of 5.1-12.4%. TPOAb-positivity may be regarded as a manifestation of a general autoimmune state which may alter the fertilization and implantation processes or cause early missed abortions. Women positive for TPOAb are at a significant risk of developing hypothyroidism during pregnancy and postpartum. Laboratory diagnosis of thyroid dysfunction during pregnancy is based upon serum TSH concentration. TSH in pregnancy is physiologically lower than the non-pregnant population. Results of multiple international studies point toward creation of trimester-specific reference intervals for TSH in pregnancy. Screening for hypothyroidism in pregnancy is controversial and its implementation varies from country to country. Currently, the case-finding approach of screening high-risk women is preferred in most countries to universal screening. However, numerous studies have shown that one-third to one-half of women with thyroid disorders escape the case-finding approach. Moreover, the universal screening has been shown to be more cost-effective. Screening for thyroid disorders in pregnancy should include assessment of both TSH and TPOAb, regardless of the screening approach. This review summarizes the current knowledge on physiology of thyroid hormones in pregnancy, causes of maternal thyroid dysfunction and its effects on pregnancy course and fetal development. We discuss the question of case-finding versus universal screening strategies and we display an overview of the analytical methods and their reference intervals in the assessment of thyroid function and thyroid autoimmunity in pregnancy. Finally, we present our results supporting the implementation of universal screening.


Assuntos
Complicações na Gravidez , Doenças da Glândula Tireoide , Feminino , Humanos , Gravidez , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/fisiopatologia , Glândula Tireoide/fisiologia , Hormônios Tireóideos
9.
J Immunol Res ; 2016: 2743614, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27872865

RESUMO

Objective. To determine the expression of chemokine receptors in lymphocytes from thyroid nodules and peripheral blood in patients with and without Hashimoto's thyroiditis (HT). Patients and Methods. The study included 46 women with thyroid nodules and HT and 60 women with thyroid nodules without HT (controls) who underwent a fine needle aspiration biopsy (FNAB). Expression of chemokine receptors CXCR3, CCR5, and CRTH2 was assessed by flow cytometry in lymphocytes from FNAB samples and from peripheral blood. Results. The percentage of CRTH2+ lymphocytes was higher in nodules with HT in comparison with controls, both in FNAB samples (13.95 versus 6.7%, p = 0.008) and in peripheral blood (6.7 versus 5.13%, p = 0.047), and positively correlated with serum antibodies to thyroid peroxidase (r = 0.243; p = 0.026) and negatively correlated with thyroid volume (r = -0.346; p = 0.008). Lymphocytes from neoplastic nodules showed a higher expression of both CXCR3 and CCR5 than those from hyperplastic ones. Conclusion. Flow cytometry performed in FNAB samples may serve as a good tool in investigation of intrathyroidal expression of immunological parameters. In our study, the CRTH2 expression on thyroid-infiltrating lymphocytes as well as on lymphocytes from peripheral blood was increased in HT as compared to controls.


Assuntos
Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Linfócitos/imunologia , Linfócitos/metabolismo , Receptores CCR5/metabolismo , Receptores CXCR3/metabolismo , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/imunologia , Adulto , Idoso , Biomarcadores , Biópsia por Agulha Fina , Estudos de Casos e Controles , Citocinas/metabolismo , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Linfócitos/patologia , Pessoa de Meia-Idade , Receptores CCR5/genética , Receptores CXCR3/genética , Receptores Imunológicos/genética , Receptores de Prostaglandina/genética , Ultrassonografia
10.
Arthritis Res Ther ; 17: 371, 2015 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-26704903

RESUMO

BACKGROUND: Autoantibodies against monomeric C-reactive protein (anti-CRP-Ab) observed in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) were suggested to be associated with active LN and a poor response to therapy during short-term follow-up. The aim of this study was to confirm this finding and to investigate the prognostic value of anti-CRP-Ab in patients with LN during long-term follow-up. METHODS: Sera of 57 SLE patients (47 women, 10 men) with biopsy proven LN and 122 healthy individuals were analyzed for the presence of anti-CRP-Ab by in-house ELISA. Anti-CRP-Ab levels were studied in relation to routine laboratory tests, urine analysis, levels of C3, C4, other immunological markers and the overall disease activity as assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The prognostic value of anti-CRP-Ab was tested in a subgroup of 29 newly diagnosed LN patients (median follow-up 5.9 years). Response to therapy at various time points was assessed with respect to baseline anti-CRP-Ab levels. At least partial response in the first/second year of treatment was considered as a "favorable outcome", while non-response, renal flare or end stage renal disease were considered as "unfavorable outcome". RESULTS: Anti-CRP-Ab were only detected in patients with active renal disease and their levels correlated with SLEDAI (rs = 0.165, p = 0.002). The time to response was shorter in patients being anti-CRP-Ab negative at baseline compared to anti-CRP-Ab positive patients, p = 0.037. In the second year of therapy, baseline anti-CRP-Ab positivity was a significant predictor of "unfavorable outcome" (OR [95% CI] = 15.6 [1.2-771]; p = 0.021). The predictive value of "baseline anti-CRP positivity" further increased when combined with "non-response to therapy in the first year". Baseline anti-CRP-Ab positivity was not a predictor of "unfavorable outcome" at the end of follow-up, (OR [95% CI] = 5.5 [0.6-71.1], p = 0.169). CONCLUSIONS: Baseline serum levels of anti-CRP-Ab seem to be a strong risk factor for a composite outcome of non-response, renal flare or end stage renal disease after two years of standard treatment of LN. The response to therapy seems to be delayed in anti-CRP-Ab positive patients.


Assuntos
Autoanticorpos/sangue , Biomarcadores/sangue , Proteína C-Reativa/imunologia , Nefrite Lúpica/imunologia , Adulto , Autoanticorpos/imunologia , Autoantígenos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Nefrite Lúpica/sangue , Masculino , Prognóstico , Índice de Gravidade de Doença
11.
Cas Lek Cesk ; 154(5): 227-31, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26612330

RESUMO

In the last 70 years, atomic disasters have occurred several times. The nuclear power plant accident at Chernobyl in 1986 in North-Central Ukraine was a unique experience in population exposures to radiation by all ages, and ongoing studies have brought a large amount of information on effects of radiation on human organism. Concerning the deteriorating global security situation and the strong rhetoric of some of the world leaders, the knowledge on the biological effects of ionizing radiation and the preventive measures designed to decrease the detrimental effects of radiation gains a new dimension, and involves all of us. This review focuses on the long-term effects of Chernobyl catastrophe especially on the endocrine system in children and in adults, and includes a summary of preventive measures in case of an atomic disaster.


Assuntos
Acidente Nuclear de Chernobyl , Doenças do Sistema Endócrino/induzido quimicamente , Sistema Endócrino/efeitos da radiação , Neoplasias Induzidas por Radiação/epidemiologia , Adulto , Criança , Feminino , Humanos , Doses de Radiação , Neoplasias da Glândula Tireoide/induzido quimicamente , Ucrânia
12.
Cas Lek Cesk ; 154(6): 287-91, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26750625

RESUMO

In the last 70 years, atomic disasters have occurred several times. The nuclear power plant accident at Chernobyl in 1986 in North-Central Ukraine was a unique experience in population exposures to radiation by all ages, and ongoing studies have brought a large amount of information effects of radiation on human organism. Concerning the deteriorating global security situation and the strong rhetoric of some of the world leaders, the knowledge on the biological effects of ionizing radiation and the preventive measures designed to decrease the detrimental effects of radiation gains a new dimension, and involves all of us. This review focuses on the long-term effects of Chernobyl catastrophe especially on the endocrine system in children and in adults, and includes a summary of preventive measures in case of an atomic disaster.


Assuntos
Acidente Nuclear de Chernobyl , Sistema Endócrino/efeitos da radiação , Lesões por Radiação/etiologia , Adulto , Neoplasias da Mama/etiologia , Criança , Feminino , Humanos , Neoplasias Induzidas por Radiação/etiologia , Guerra Nuclear , Política , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Doses de Radiação , Risco , Neoplasias da Glândula Tireoide/etiologia , Ucrânia
13.
PLoS One ; 9(10): e110878, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25350671

RESUMO

BACKGROUND: Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences the course of pregnancy. Autoimmune thyroid diseases (AITD) belong to the well-defined risk factors for adverse pregnancy outcomes. The aim of this study was to investigate whether there is a link between latent toxoplasmosis and maternal AITD in pregnancy. METHODS: Cross-sectional study in 1248 consecutive pregnant women in the 9-12th gestational weeks. Serum thyroid-stimulating hormone (TSH), thyroperoxidase antibodies (TPOAb), and free thyroxine (FT4) were assessed by chemiluminescence; the Toxoplasma status was detected by the complement fixation test (CFT) and anti-Toxoplasma IgG enzyme-linked immunosorbent assay (ELISA). RESULTS: Overall, 22.5% of the women were positive for latent toxoplasmosis and 14.7% were screened positive for AITD. Women with latent toxoplasmosis had more often highly elevated TPOAb than the Toxoplasma-negative ones (p = 0.004), and latent toxoplasmosis was associated with decrease in serum TSH levels (p = 0.049). Moreover, we found a positive correlation between FT4 and the index of positivity for anti-Toxoplasma IgG antibodies (p = 0.033), which was even stronger in the TPOAb-positive Toxoplasma-positive women, (p = 0.014), as well as a positive correlation between FT4 and log2 CFT (p = 0.009). CONCLUSIONS: Latent toxoplasmosis was associated with a mild increase in thyroid hormone production in pregnancy. The observed Toxoplasma-associated changes in the parameters of AITD are mild and do not seem to be clinically relevant; however, they could provide new clues to the complex pathogenesis of autoimmune thyroid diseases.


Assuntos
Doenças Autoimunes/etiologia , Complicações na Gravidez/etiologia , Doenças da Glândula Tireoide/etiologia , Toxoplasmose/complicações , Adolescente , Adulto , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Doenças Autoimunes/epidemiologia , Estudos Transversais , República Tcheca/epidemiologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Pessoa de Meia-Idade , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Fatores de Risco , Doenças da Glândula Tireoide/epidemiologia , Hormônios Tireóideos/sangue , Toxoplasmose/diagnóstico , Adulto Jovem
14.
J Neuroimmunol ; 274(1-2): 185-91, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25109258

RESUMO

The role of complement has been demonstrated in experimental models of neuromyelitis optica (NMO), however, only few studies have analysed complement components longitudinally in NMO patients. We measured serum or plasma concentrations of anti-C1q antibodies and complement split products C3a and C4a and soluble C5b-9 in patients with NMO, multiple sclerosis and healthy controls. NMO patients had higher levels of C3a and anti-C1q antibodies than healthy controls. C3a levels correlated with disease activity, neurological disability and aquaporin-4 IgG in NMO patients suggesting a role of the alternative pathway of complement in the pathogenesis of NMO and supporting the strategy of therapeutic complement inhibition.


Assuntos
Ativação do Complemento/imunologia , Complemento C1q/imunologia , Complemento C3a/imunologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Neuromielite Óptica/imunologia , Adolescente , Adulto , Idoso , Aquaporina 4/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Complemento C1q/metabolismo , Complemento C3a/metabolismo , Feminino , Seguimentos , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
15.
Clin Endocrinol (Oxf) ; 80(3): 452-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23889327

RESUMO

OBJECTIVE: Iodine deficiency is associated with thyroid dysfunction and adverse pregnancy outcomes. The aim of our study was to investigate the status of iodine saturation in women after spontaneous abortion (SpA) residing in an iodine-sufficient area and to evaluate their subsequent reproductive health. DESIGN: Nonrandomized prospective follow-up study. PATIENTS AND METHODS: We compared urinary iodine concentration (UIC) in 171 women 2-8 weeks (median 4) after an early SpA with age-matched controls. Women with known thyroid diseases were excluded. We also analysed a relationship of UIC to serum thyroid-stimulating hormone, free thyroxine, antibodies against thyroid peroxidase and thyroid ultrasound. Afterwards, we followed the women for a median of 38 months (range 12-47). We used a multivariate regression analysis to assess the influence of iodine status and other thyroid biochemical and ultrasound parameters on their subsequent reproductive health. RESULTS: Women after SpA were almost twice as likely to suffer from mild iodine deficiency and had lower median UIC as compared to age-matched controls [rate 105/181 (58·0%) vs 57/181 (31·5%), P < 0·001, medians UIC 92·00 vs 117·80 mcg/l, P < 0·001]. UIC was not influenced by the use of iodine supplements in the previous pregnancy. We did not find any association neither between UIC and thyroid dysfunction and/or thyroid antibodies, nor between UIC and rates of subsequent successful pregnancies or obstetric complications. CONCLUSIONS: More than half of women after SpA residing in an iodine-sufficient area are suffering from mild iodine deficiency. However, it does not seem to have a negative impact on their subsequent reproductive health.


Assuntos
Aborto Espontâneo/epidemiologia , Deficiências Nutricionais/epidemiologia , Iodo/deficiência , Aborto Espontâneo/etiologia , Aborto Espontâneo/urina , Adulto , Estudos de Casos e Controles , República Tcheca/epidemiologia , Deficiências Nutricionais/complicações , Feminino , Seguimentos , Humanos , Iodo/provisão & distribução , Iodo/urina , Gravidez , Prevalência , Saúde Reprodutiva/estatística & dados numéricos , Índice de Gravidade de Doença
16.
PLoS One ; 8(12): e81755, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24339961

RESUMO

Functional deficiency of mannan-binding lectin (MBL) has been associated with adverse pregnancy outcome. Adverse events during pregnancy have also been described in women with autoimmune thyroid diseases (AITD), and thyroid hormones have been shown to influence serum levels of MBL. Therefore, the aim of this study was to analyse the impact of MBL-deficiency on the outcome of pregnancy in relation to the presence of AITD. Almost one year after delivery, we assessed serum MBL levels and MBL2-genotypes in 212 women positively screened for AITD in pregnancy. In 103 of these women, we could also measure MBL levels in frozen serum samples from the 9-12(th) gestational week, obtaining 96 pairs of MBL values (pregnancy vs. follow-up). As controls, 80 sera of pregnant women screened negatively for AITD were used. MBL2-genotyping was performed using multiplex PCR. Women with thyroid dysfunction and/or thyroid peroxidase antibodies (TPOAb) had lower MBL levels during pregnancy than controls, (3275 vs. 5000 ng/ml, p<0.05). The lowest levels were found in women with elevated thyroid-stimulating hormone (TSH) levels in the absence of TPOAb (2207 ng/ml; p<0.01 as compared to controls). MBL2 genotype distribution did not differ between subgroups. At a median follow-up period of 17 months (range: 3-78 months) after delivery, median MBL level had decreased further to 1923 ng/ml (p<0.0001) without significant changes in TSH. In an explorative survey, functional MBL-deficiency was neither linked to a history of spontaneous abortion, nor other obstetric complications, severe infections throughout life/pregnancy or antibiotics use in pregnancy. In conclusion, hypothyroidism during pregnancy is associated with decreased MBL levels, and the levels decreased further after delivery.


Assuntos
Lectina de Ligação a Manose/sangue , Complicações na Gravidez/sangue , Resultado da Gravidez , Primeiro Trimestre da Gravidez/sangue , Tireoidite Autoimune/sangue , Adulto , Autoanticorpos/sangue , Autoantígenos/sangue , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Iodeto Peroxidase/sangue , Proteínas de Ligação ao Ferro/sangue , Gravidez , Estudos Retrospectivos , Tireotropina/sangue
17.
BMC Pregnancy Childbirth ; 13: 217, 2013 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-24267864

RESUMO

BACKGROUND: Hypothyroidism and/or autoimmune thyroid disorders (AITD) may contribute to spontaneous abortions (SpA). Cost-effectiveness analyses of thyroid screening in women after SpA are lacking. Our aim was to evaluate the cost-effectiveness of screening for AITD and/or hypothyroidism and their treatment in women after SpA with regard to their reproductive health. METHODS: We performed a cross-sectional non-randomized study with follow-up in 2008-2011 in the settings of Departments of Endocrinology and Obstetrics/Gynecology of a university hospital. We enrolled 258 women after SpA before the 12th gestational week and followed them for a median of 3 years. At enrollment, serum concentrations of thyroid stimulatory hormone (TSH), antibodies to thyroid peroxidase (TPOAb) and free thyroxine (FT4) were measured and thyroid ultrasound performed. Women with overt hypothyroidism were treated with levothyroxine (n = 45; 61.6%) and women with subclinical hypothyroidism or euthyroid AITD were treated (n = 28; 38.4%) or left untreated (n = 38; 14.7%). Euthyroid women without signs of AITD served as controls (n = 147; 57.0%). RESULTS: Of the 38 untreated women with AITD and/or subclinical hypothyroidism, 8 (21.1%) reported secondary infertility as compared to 16/147 (10.9%) controls and 3/73 (4.1%) treated women (p = 0.021). Treatment was associated with an increased rate of successfully completed subsequent pregnancies (increment of 6 newborns/100 women) and a savings of €19,539/100 women. Total costs per successfully completed pregnancy were €1,189 in controls, €1,564 in the treated, and €2,488 in the untreated women. CONCLUSIONS: Screening for thyroid disorders in women after SpA and treatment with levothyroxine is cost-saving and it improves the subsequent pregnancy rate.


Assuntos
Aborto Espontâneo/etiologia , Doenças Autoimunes/diagnóstico , Hipotireoidismo/diagnóstico , Programas de Rastreamento/economia , Tiroxina/uso terapêutico , Adulto , Autoanticorpos/sangue , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Análise Custo-Benefício , Estudos Transversais , Feminino , Seguimentos , Humanos , Hipotireoidismo/complicações , Hipotireoidismo/tratamento farmacológico , Infertilidade Feminina/etiologia , Iodeto Peroxidase/imunologia , Gravidez , Taxa de Gravidez , Tireotropina/sangue , Tiroxina/sangue , Tiroxina/economia
18.
Clin Chem Lab Med ; 50(7): 1211-20, 2012 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-22850054

RESUMO

The aim of general maternal-foetal care is to ensure an uncomplicated birth of a healthy baby to a healthy mother. There is a large range of screening tests used during pregnancy: for gestational diabetes, infection, rhesus-D status, thyroid dysfunction, as well as other tests. An important part of prenatal care is the screening of major aneuploidies, primarily for Down's syndrome. This screening is possible in either the first or second trimester, or in both. Management of this type of screening is very similar around the world. Hypothyroidism can affect the psychomotor development of the child. Thyroid-stimulating hormone (TSH), autoantibodies against thyroperoxidase (TPOAb), and free thyroxin (FT4) were determined within our group of 7530 pregnant women. Elevated concentrations of TSH were found in 5.1%, suppression was found in 2.9% and 11.5% were TPOAb positive. Either a familial or personal history of thyroid or autoimmune diseases was present in 58.3% of those women who tested positive on any thyroid test. At minimum, 40% of women TPOAb positive during pregnancy have some kind of thyroid disorders after delivery. These results support the efficacy of general thyroid function screening in early pregnancy, as well as the follow-up after delivery of those women who are positive.


Assuntos
Síndrome de Down/diagnóstico , Diagnóstico Pré-Natal/métodos , Doenças da Glândula Tireoide/diagnóstico , Testes de Função Tireóidea/métodos , Feminino , Humanos , Gravidez
20.
J Clin Endocrinol Metab ; 97(6): 1945-52, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22438224

RESUMO

CONTEXT: The guidelines of American Thyroid Association from 2011 include age over 30 as one of the risk factors for hypothyroidism in pregnancy. OBJECTIVE: Our objective was to verify whether age increases the risk of autoimmune thyroid disease in pregnancy. DESIGN: We performed a cross-sectional study in 2006-2008 with laboratory assessment in a single center using primary care gynecological ambulances in cooperation with a referral center. PATIENTS: The study included 5223 consecutive pregnant women in gestational wk 9-12. MAIN OUTCOME MEASURE: We assessed the occurrence of pathological serum concentrations of TSH and/or antibodies against thyroperoxidase (TPOAb) with regard to age. Reference interval for TSH was 0.06-3.67 mU/liter; the upper cutoff value for TPOAb was 143 kU/liter. RESULTS: Overall, 857 women (16.4%) were positively screened. Of these, 294 (5.63%) had TSH elevation, 146 (2.79%) had TSH suppression, 561 (10.74%) were TPOAb positive, and 417 (7.98%) were euthyroid and TPOAb positive. The average age of women was 31.1 yr. The prevalence of hypothyroidism was 5.5 and 5.8% in women aged 30 or older and those under 30 yr, respectively (P value nonsignificant). Using a logistic regression model, we didn't find any significant association between age and serum TSH suppression, TSH elevation, or TPOAb positivity (P = 0.553, P = 0.680, and P = 0.056, respectively) or between age and TSH elevation with TPOAb positivity (P = 0.967). In a subgroup analysis of risk factors for hypothyroidism in 132 hypothyroid women, addition of age 30 or older increased the proportion of women identified in a case-finding screening strategy from 55.3 to 85.6%. CONCLUSIONS: Prevalence of autoimmune thyroid disease does not increase with age in pregnant women; however, addition of age 30 or over to the case-finding screening strategy may substantially improve its efficiency due to a larger number of women screened.


Assuntos
Hipotireoidismo/epidemiologia , Complicações na Gravidez/epidemiologia , Tireoidite Autoimune/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Autoanticorpos/sangue , Estudos Transversais , Feminino , Humanos , Hipotireoidismo/imunologia , Iodeto Peroxidase/imunologia , Gravidez , Complicações na Gravidez/imunologia , Primeiro Trimestre da Gravidez/imunologia , Prevalência , Fatores de Risco , Tireoidite Autoimune/imunologia , Tireotropina/sangue , Adulto Jovem
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