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1.
J Matern Fetal Neonatal Med ; : 1-11, 2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31957515

RESUMO

Objective: To ascertain the most effective approach in pregnancies complicated by mild intrahepatic cholestasis of pregnancy (mICP) by evaluating rates of adverse perinatal outcomes (APOs) and pathological placental findings.Methods: A total of 89 pregnancies complicated by mICP (defined as total serum bile acids (TSBAs) levels <40 µmol/L) were included. One-drug (ursodeoxycholic acid [UDCA]) (n = 49, 55.1%) and combined (UDCA plus S-adenosyl methionine (SAMe)) (n = 40, 44.9%) therapies were compared.Results: No differences were found in demographic, obstetric, and placental characteristics. In UDCA plus SAMe group, premature delivery was a common clinical decision (14.3 versus 25%, p-value = .201), with increased rates of instrumental vaginal delivery (VD; 28.6 versus 40%, p-value = .522), but similar cesarean section (CS) rates (26.5 versus 25%, p-value = .498). Mean placental weight was comparable (UDCA, mean 595.7 g, SD 213.1 g versus UDCA plus SAMe, mean 586.4 g, SD 102.9 g, p-value = .875). A total of 110 lesions were identified, 64 in 25 placentas of patients assigned to the UDCA and 46 in 15 placentas of patients managed by UDCA plus SAMe. Placental findings attributable to maternal malperfusion were found in 41/25 and 32/15 cases treated by UCDA and UDCA plus SAMe (165 versus 213%, p-value = .774), pathological fetal vascular supply in 17/25 and 8/15 placentas (68 versus 53%, p-value = .777), and inflammatory lesions in 6/25 and 6/15 cases (24 versus 40%, p-value = .757).Conclusions: Pregnancies complicated by mICP and managed by UDCA alone present similar APO rates and placental histopathology if compared with those treated by UDCA plus SAMe, failing to recognize advantages in the combined therapy. Further prospective studies and data sharing from ongoing RTCs could drive changes in therapeutic plan.

2.
Clin Chim Acta ; 496: 25-34, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31201817

RESUMO

BACKGROUND: The study aim is to compare cTnI values measured with three high-sensitivity (hs) methods in apparently healthy volunteers and patients admitted to emergency department (ED) with acute coronary syndrome enrolled in a large multicentre study. METHODS: Heparinized plasma samples were collected from 1511 apparently healthy subjects from 8 Italian clinical institutions (mean age: 51.5 years, SD: 14.1 years, range: 18-65 years, F/M ratio:0.95). All volunteers denied chronic or acute diseases and had normal values of routine laboratory tests. Moreover, 1322 heparinized plasma sample were also collected by 9 Italian clinical institutions from patients admitted to ED with clinical symptoms typical of acute coronary syndrome. The reference study laboratory assayed all plasma samples with three hs-methods: Architect hs-cTnI, Access hs-cTnI and ADVIA Centaur XPT methods. Principal Component Analysis (PCA) was also used to analyze the between-method differences among hs-cTnI assays. RESULTS: On average, a between-method difference of 31.2% CV was found among the results of hs-cTnI immunoassays. ADVIA Centaur XPT method measured higher cTnI values than Architect and Access methods. Moreover, 99th percentile URL values depended not only on age and sex of reference population, but also on the statistical approach used for calculation (robust non-parametric vs bootstrap). CONCLUSIONS: Due to differences in concentrations and reference values, clinicians should be advised that plasma samples of the same patient should be measured for cTnI assay in the same laboratory. Specific clinical studies are needed to establish the most appropriate statistical approach to calculate the 99th percentile URL values for hs-cTnI methods.


Assuntos
Síndrome Coronariana Aguda/sangue , Análise Química do Sangue/métodos , Serviço Hospitalar de Emergência , Voluntários Saudáveis , Limite de Detecção , Miocárdio/metabolismo , Troponina I/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Química do Sangue/normas , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Valores de Referência , Adulto Jovem
4.
Clin Chim Acta ; 495: 161-166, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30978328

RESUMO

BACKGROUND: According to quality specifications required by international guidelines, the evaluation of the 99th URL value is a very difficult task that is usually beyond the capacity of a single laboratory. The aims of this article are to report and discuss the results of a multicenter study concerning the evaluation of the 99th percentile URL and reference change (RCV) of the ADVIA Centaur High-Sensitivity Troponin I (TNIH), recently distributed to the Italian clinical laboratories. MATERIALS AND METHODS: The reference population evaluated with ADVIA XPT method for the calculation of cTnI reference distribution parameters consisted of 1325 healthy adults subjects (age range from 18 to 86 years), including 653 women (mean age 50.7 years, SD 14.5 years) and 672 men (mean age 50.9 years, SD 13.8 years), well matched for both age (P = .8112) and sex (F/M = 0.97). RESULTS: cTnI distribution values of reference population was highly skewed, while log-transformed cTnI values roughly approximated a log-normal distribution. Men have higher cTnI values than women throughout all the adult lifespan. Moreover, the subjects with age ≤ 55 years had significantly lower cTnI values than those with age > 55 years (p < .0001). Of note, 62% of women and 77% of men had equal or higher than cTnI values than the LoD value of the method (i.e., 2.2 ng/L). CONCLUSIONS: The results of the present study demonstrate that the ADVIA Centaur High-Sensitivity Troponin I using the XPT automated platform fits both the criteria and quality specifications required by the most recent international guidelines for high-sensitivity methods for cTnI assay.


Assuntos
Análise Química do Sangue/normas , Miocárdio/metabolismo , Troponina I/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoensaio/normas , Masculino , Pessoa de Meia-Idade , Valores de Referência , Troponina I/metabolismo , Adulto Jovem
5.
Clin Chim Acta ; 493: 156-161, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30826369

RESUMO

BACKGROUND: The Italian Society of Clinical Biochemistry (SIBioC) and the Italian Section of the European Ligand Assay Society (ELAS) have recently promoted a multicenter study (Italian hs-cTnI Study) with the aim to accurately evaluate analytical performances and reference values of the most popular cTnI methods commercially available in Italy. The aim of this article is to report the results of the Italian hs-cTnI Study concerning the evaluation of the 99th percentile URL and reference change (RCV) values around the 99th URL of the Access cTnI method. MATERIALS AND METHODS: Heparinized plasma samples were collected from 1306 healthy adult volunteers by 8 Italian clinical centers. Every center collected from 50 to 150 plasma samples from healthy adult subjects. All volunteers denied the presence of chronic or acute diseases and had normal values of routine laboratory tests (including creatinine, electrolytes, glucose and blood counts). An older cohort of 457 adult subjects (mean age 63.0 years; SD 8.1 years, minimum 47 years, maximum 86 years) underwent also ECG and cardiac imaging analysis in order to exclude the presence of asymptomatic cardiac disease. RESULTS AND CONCLUSIONS: The results of the present study confirm that the Access hsTnI method using the DxI platform satisfies the two criteria required by international guidelines for high-sensitivity methods for cTn assay. Furthermore, the results of this study confirm that the calculation of the 99th percentile URL values are greatly affected not only by age and sex of the reference population, but also by the statistical approach used for calculation of cTnI distribution parameters.


Assuntos
Técnicas de Imagem de Sincronização Cardíaca/normas , Eletrocardiografia/normas , Troponina I/sangue , Troponina T/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Voluntários Saudáveis , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
6.
Clin Chem Lab Med ; 56(3): 397-402, 2018 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-29220884

RESUMO

It is well known that the results of immunoassay methods can be affected by specific or non-specific interferences, ranging from 0.4% to 4.0%. The presence of interference may greatly compromise the accuracy of immunoassay analyses causing an error in the measurement, producing false-positive or false-negative results. From a clinical point of view, these analytical errors may have serious implications for patient care because they can cause misdiagnosis or inappropriate treatment. Unfortunately, it is a very difficult task to identify the irregular analytical errors related to immunoassay methods because they are not detectable by normal laboratory quality control procedures, are reproducible within the test system, may be clinically plausible and are relatively rare. The first line of defense against erroneous results is to use in laboratory practice only immunoassay systems with the highest level of robustness against interference. The second line of defense is always taking into account the possibility of interference in immunoassay results. A correct approach should be addressed on identification of samples at high risk of interference. The attainment of this goal requires a critical review of the test result in relation to patient's clinical conditions and literature data, taking into account the analytical characteristics of the immunoassay system. The experts in immunoassay systems should make every effort to find some specific and reliable quality indicators for irregular analytical errors in order to better detect and monitor erroneous immunoassay results due to specific or non-specific interferences.


Assuntos
Técnicas de Laboratório Clínico , Erros de Diagnóstico , Imunoensaio , Humanos , Controle de Qualidade
7.
Metabolism ; 71: 46-51, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28521877

RESUMO

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase gene (CYP21A2). Most of CYP21A2 mutations result from intergenic recombinations between CYP21A2 and closely linked CYP21A1P pseudogene. Rare mutations not generated by gene conversion account for 5-10% of 21-hydroxylase deficiency alleles. Intronic variants represent only a little part of these but their effect on the protein is generally deleterious. The aim of this paper is to provide a comprehensive literary review regarding all intronic CYP21A2 pathological variants reported to date. In addition, we describe three novel causing disease variants in our patients affected by the classic form of CAH: IVS4-1G>A, IVS5-8T>A, IVS8-2A>G. In silico analysis revealed that all these substitutions affect the splicing process leading to a non-functional protein. Based on these results, we are able to classify them as pathological variants according to the patient's phenotype.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Esteroide 21-Hidroxilase/genética , Variação Genética , Humanos , Íntrons/genética , Patologia Molecular , Esteroide 21-Hidroxilase/metabolismo
8.
Clin Chem Lab Med ; 55(11): 1722-1733, 2017 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-28245185

RESUMO

BACKGROUND: Systematic difference between thyroid-stimulating hormone (TSH) immunoassays may produce misleading interpretation when samples of the same patients are measured with different methods. The study aims were to evaluate whether systematic differences are present among TSH immunoassays, and whether it is possible to obtain a better harmonization among TSH methods using results obtained in external quality assessment (EQA) schemes. METHODS: Seven Italian clinical laboratories measured TSH in 745 serum samples of healthy subjects and patients with thyroid disorders. These samples were also re-measured by two reference laboratories of the study with the six TSH immunoassays most popular in Italy after 2 months of storage at -80 °C. Moreover, these data were compared to 53,823 TSH measurements, obtained by laboratories participant to 2012-2015 EQA annual cycles in 72 quality control samples (TSH concentrations from about 0.1 mIU/L to 18.0 mIU/L). TSH concentrations were recalibrated using a mathematical approach based on the principal component analysis (PCA). RESULTS: Systematic differences were found between the most popular commercially available TSH immunoassays. TSH concentrations measured by the clinical laboratories were very closely correlated to those measured with the same method by reference laboratories after 2 months of storage at -80 °C. After recalibration using the PCA approach the variation of TSH values significantly decreased from a median pre-calibration value of 13.53% (10.79%-16.53%) to 9.63% (6.90%-13.21%) after recalibration. CONCLUSIONS: Our data suggest that EQA schemes are useful to improve harmonization among TSH immunoassays and also to produce some mathematical formulas, which can be used by clinicians to better compare TSH values measured with different methods.


Assuntos
Imunoensaio/métodos , Tireotropina/sangue , Calibragem , Humanos , Imunoensaio/normas , Laboratórios/normas , Modelos Lineares , Análise de Componente Principal , Controle de Qualidade , Kit de Reagentes para Diagnóstico , Doenças da Glândula Tireoide/diagnóstico , Tireotropina/normas
9.
Clin Chim Acta ; 468: 105-110, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28189596

RESUMO

AIM OF THE STUDY: Recently, Beckman Coulter Diagnostics set up a new TSH immunoassay for the automated DxI platform. The aim of this study was to evaluate and compare the analytical performance and clinical results of this method with those of previous method. MATERIAL AND METHODS: A multicenter study (named TSH ELAS Study) was organized using 593 serum samples, collected from healthy subjects and patients with thyroid disorders, and 13 control samples, circulated in an External Quality Assessment (EQA) scheme. RESULTS: The values of LoB and LoD, and LoQ at 20% CV were 0.0004mIU/L, 0.001mIU/L and 0.0023mIU/L, respectively. Moreover, TSH concentrations >0.01mIU/L actually show imprecision values lower than 5% CV. This new TSH assay showed a systematic underestimation (on average of 6.25%) compared to old method, which is mainly due to larger differences between methods for samples with low TSH concentrations, related to the better analytical sensitivity of new compared to old method. In a reference population, including 279 apparently healthy adult subjects, Caucasian volunteers (mean age 43.6years, age 20-63years, 138 women and 141 males) the distribution of TSH concentrations was: mean (CI 95%) 1.694mIU/L (1.588-1.779), median 1.495mIU/L (1.412-1.588mIU/L), 97.5th percentile 3.707mIU/L. CONCLUSIONS: The new TSH immunoassay for DxI platform shows some relevant improvements compared to the previous one: use of the most recent WHO 3rd IRP 81/563 standard and monoclonal antibodies (instead of polyclonal antibodies of the old method), and better analytical sensitivities and reproducibility.


Assuntos
Imunoensaio/métodos , Tireotropina/sangue , Adulto , Automação , Estudos de Casos e Controles , Feminino , Humanos , Imunoensaio/normas , Masculino , Pessoa de Meia-Idade , Controle de Qualidade , Valores de Referência , Reprodutibilidade dos Testes , Neoplasias da Glândula Tireoide/sangue , Adulto Jovem
11.
Surgery ; 159(1): 70-6, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26456123

RESUMO

BACKGROUND: Intraoperative measurement of calcitonin is not highly accurate in predicting the completeness of the operative resection after total thyroidectomy combined with central neck dissection (TT-CND) in patients with medullary thyroid carcinoma (MTC). We evaluated whether an intraoperative, high-dose calcium stimulation test (IO-CST) after TT-CND can predict lateral neck involvement. METHODS: Eleven patients who underwent primary operation for sporadic MTC were included. High-dose (25 mg/kg) calcium gluconate was administered after TT-CND with calcitonin measured at 2, 5, and 10 minutes after the calcium gluconate infusion. RESULTS: There were 2 males and 9 females (mean age, 51 years; range, 18-88). Three patients showed lateral neck metastases. At a mean follow-up of 7.0 months (range, 2-10), 1 patient showed distant metastases and 1 a slightly increased calcitonin level. After IO-CST, serum calcitonin increased in all the 3 patients with lateral neck metastases, and it remained unchanged or decreased in the other patients without lateral neck metastases. Percent variation of serum calcitonin after IO-CST was 92% in patients with lateral neck metastases and -3.1 ± 4.9% in patients without lateral neck metastases. CONCLUSION: Calcitonin measurement after IO-CST in patients with sporadic MTC can be highly accurate in predicting lateral neck nodes involvement. These results could represent a stimulus toward the development of a quick calcitonin assay.


Assuntos
Calcitonina/sangue , Cálcio/administração & dosagem , Carcinoma Neuroendócrino/cirurgia , Metástase Linfática/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcitonina/metabolismo , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/metabolismo , Feminino , Humanos , Cuidados Intraoperatórios , Excisão de Linfonodo , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Pescoço , Esvaziamento Cervical , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/metabolismo , Tireoidectomia , Adulto Jovem
12.
Surgery ; 159(1): 78-84, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26456131

RESUMO

BACKGROUND: Hypocalcemia may develop even in the presence of normal postoperative parathyroid hormone (PTH) concentrations. We aimed to identify risk factors of hypocalcemia in patients with normal PTH concentration early after total thyroidectomy (TT). METHODS: We included 1,504 consecutive patients who underwent TT between January 2012 and December 2013. Significant hypocalcemia was defined as serum calcium concentrations of <8.0 mg/dL. RESULTS: Overall, 333 patients had subnormal PTH 4 hours after surgery (4-hour PTH; <10 pg/mL) and received oral calcium (OC) and calcitriol supplementation. Among the 1,171 patients with normal 4-hour PTH (≥ 10 pg/mL; euparathyroid), 211 experienced hypocalcemia and required OC administration. Among the euparathyroid patients, no difference was found between normocalcemic and hypocalcemic patients in terms of age, hormonal status, preoperative PTH, 25-hydroxy vitamin D (25OH-VD), magnesium, and phosphate concentrations. On univariate analysis, euparathyroid hypocalcemic patients were more frequently females, had significantly lower preoperative serum calcium and 4-hour PTH concentrations, and greater decreases in PTH. Independent risk factors for hypocalcemia with normal 4-hour PTH were preoperative serum calcium concentration and PTH decline of ≥ 50%. CONCLUSION: Female sex, toxic goiter, and 25OH-VD deficiency are not risk factors for post-TT hypocalcemia. Relative parathyroid insufficiency seems to be the principal mechanism of post-thyroidectomy hypocalcemia, even in patients with normal postoperative PTH concentrations.


Assuntos
Cálcio/sangue , Hipocalcemia/etiologia , Hipoparatireoidismo/sangue , Hormônio Paratireóideo/sangue , Tireoidectomia/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Hipocalcemia/sangue , Hipoparatireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Adulto Jovem
13.
Eur J Prev Cardiol ; 22(7): 855-63, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24821730

RESUMO

BACKGROUND: Gonadal function is thought to be involved in existing atherosclerotic plaques stabilization and might affect reperfusion after primary percutaneous coronary intervention (pPCI). We aimed to compare the prevalence of hypotestosteromenia between ST-elevation myocardial infarction (STEMI) and stable angina (SA) patients and between patients with and without microvascular obstruction (MVO). DESIGN: Cross-sectional observational study. METHODS: Males with STEMI (n = 70, age 57.1 ± 7.8 years) or with stable angina (n=30, age 59.9 ± 8.4 years) were enrolled. Angiographic MVO (angio-MVO) was defined as final TIMI flow 2 or final TIMI flow 3 with MBG ≤ 2 while electrocardiographic MVO (ECG-MVO) as a ST-segment resolution <70% at 90 minutes post-pPCI. Variables associated with STEMI and MVO were assessed among clinical, angiographic and laboratory data including testosterone (T) and insulin-like factor 3 (INSL-3), a marker of Leydig cells function. Hypotestosteronemia was defined as T<2.50 ng/ml with INSL-3<305.5 pg/ml. RESULTS: Hypotestosteronemia was detected in 32 (45.7%) STEMI patients and in 4 (13.3%) SA patients (p=0.003). STEMI patients presenting with angio-MVO were more frequently hypotestosteronemic as compared with those without (60.9% vs 38.3%, p=0.043). Hypotestosteronemia prevalence was higher among STEMI patients presenting with ECG-MVO as compared with those without (69.0% vs 31.7%, p=0.003). At multivariate analysis hypotestosteronemia independently predicted both angio-MVO (OR=4.47, 95% CI 1.30-15.36, p=0.018) and ECG-MVO (OR=7.56, 95% CI 2.20-25.99, p=0.001). CONCLUSIONS: Our study shows higher prevelence of hypotestosteronemia among STEMI patients as compared with SA patients and among STEMI patients with MVO as compared with those without, thus suggesting a possible role of T deficiency in coronary instability and MVO pathogenesis.


Assuntos
Angina Estável/sangue , Circulação Coronária , Microcirculação , Infarto do Miocárdio/sangue , Testosterona/sangue , Testosterona/deficiência , Idoso , Angina Estável/diagnóstico , Angina Estável/epidemiologia , Angina Estável/fisiopatologia , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Angiografia Coronária , Estudos Transversais , Eletrocardiografia , Humanos , Itália/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/fisiopatologia , Razão de Chances , Prevalência , Estudos Prospectivos , Fatores de Risco
15.
World J Surg ; 38(3): 568-75, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24253105

RESUMO

BACKGROUND: The extension of the compartment-oriented neck dissection at primary surgery in medullary thyroid carcinoma (MTC) is controversial. Because a <50 % decrease in intraoperative calcitonin levels (IO-CT) after total thyroidectomy plus central neck dissection (TT-CND) has been associated with residual disease, IO-CT monitoring has been proposed to predict the completeness of surgery. The goal of the present prospective study was to verify the accuracy of IO-CT monitoring. METHODS: All patients scheduled for primary surgery for suspected or proven MTC between November 2010 and January 2013 were included. Calcitonin was measured pre-incision (basal level), after tumor manipulation, at the time TT-CND was accomplished (ablation level), 10 and 30 min after ablation. A decrease >50 % with respect to the highest IO-CT level 30 min after ablation was considered predictive of cure. RESULTS: Twenty-six patients were included, and IO-CT monitoring identified 18 of 23 cured patients (true negative results) and 2 of 3 patients with persistent disease (true positive result). In 5 patients with normal basal and stimulated postoperative calcitonin levels, a decrease <50 % was observed (false positive results). In one of three patients with persistent disease a >50 % decrease in IO-CT was observed (false negative results). Specificity, sensitivity, and accuracy of IO-CT were 78.2, 66.6, and 76.9 %, respectively. CONCLUSIONS: Intraoperative calcitonin monitoring is not highly accurate in predicting the completeness of surgical resection. In the present series, relying on IO-CT would result in limited resection in about one third of the patients with residual neck disease and in unnecessary lateral neck dissection in about 20 % of the cured patients.


Assuntos
Calcitonina/sangue , Carcinoma Medular/cirurgia , Monitorização Intraoperatória , Esvaziamento Cervical , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto , Idoso , Biomarcadores/sangue , Carcinoma Medular/sangue , Carcinoma Neuroendócrino , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/sangue , Resultado do Tratamento
16.
PLoS One ; 8(1): e52585, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23300980

RESUMO

It is now well established that major depression is accompanied and characterized by altered responses of the immune-inflammatory system. In this study we investigated the pro-inflammatory activation of monocytes isolated from depressed patients as a parameter not influenced by such confounds as the time of day, the nutritional and exercise status or the age and gender of patients. Monocytes from depressed patients and from healthy controls were isolated in vitro; after 24-h incubation under basal conditions, cells were exposed for 24-h to 100 ng/ml of endotoxin (bacterial lipopolysaccharide, LPS). We found that monocytes from drug-free depressed patients and controls release the same amounts of prostaglandin E2 (PGE2) under basal conditions, whereas monocytes from patients are dramatically less reactive to LPS (8.62-fold increase vs previous 24 hrs) compared to healthy controls (123.3-fold increase vs previous 24 hrs). Such blunted prostanoid production was paralleled by a reduction in COX-2 gene expression, whereas other pro-inflammatory mediators, namely interleukin-1ß (IL-1 ß) and -6 (IL-6) showed a trend to increased gene expression. The above changes were not associated to increased levels of circulating glucocorticoids. After 8 months of antidepressive drug treatment, the increase in PGE2 production after the endotoxin challenge was partially restored, whereas the increase in IL-1 ß and -6 levels observed at baseline was completely abolished. In conclusion, our findings show that the reactivity of monocytes from depressed patients might be considered as a marker of the immune-inflammatory disorders associated to depression, although the lack of paired healthy controls at follow-up does not allow to conclude that monocyte reactivity to endotoxin is also a marker of treatment outcome.


Assuntos
Depressão/sangue , Depressão/imunologia , Endotoxinas/farmacologia , Regulação da Expressão Gênica , Monócitos/efeitos dos fármacos , Adulto , Estudos de Casos e Controles , Ritmo Circadiano , Citosol/fisiologia , Dexametasona/farmacologia , Dinoprostona/metabolismo , Endotoxinas/metabolismo , Feminino , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Inflamação , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Saliva/fisiologia , Fatores de Tempo
17.
Hormones (Athens) ; 11(3): 344-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22908067

RESUMO

OBJECTIVE: Mitotane is an adrenocytolytic agent used in adrenocortical carcinoma, inducing adrenal insufficiency, requiring replacement treatment. Such therapy is not easy to monitor because of mitotane interference. Salivary cortisol reflects a free fraction of plasma cortisol and may be useful in such patients. DESIGN: The aim of our study was to evaluate salivary cortisol by HPLC coupled to tandem-mass spectrometry (LC-MS/MS) and by an electrochemiluminescence immunoassay (ECLIA) in patients treated with mitotane. We enrolled 6 patients receiving mitotane and 2 Addison disease patients as negative controls and determined salivary cortisol rhythm. We also determined the salivary cortisol rhythm in 8 healthy subjects. Salivary samples (n=112) were assayed by ECLIA, using Roche Modular E170, and by LC-MS/MS. RESULTS: The mean values obtained by ECLIA were significantly higher than those obtained by LC-MS/MS in the mitotane group (p<0.001). In fact, in the group measured by LC-MS/MS, we observed several peaks eluting at a retention time different from the cortisol group, presumably due to cortisol-like analogues. In Addison disease, since steroidogenesis is absent, salivary cortisol values measured by the two methods did not show any significant difference (p=0.61). CONCLUSIONS: Salivary cortisol measured by LC-MS/MS is a selective method, excluding cortisol analogues accumulating in treated patients. Therefore, LC-MS/MS offers an effective system to monitor replacement therapy in mitotane treated patients.


Assuntos
Hidrocortisona/análise , Mitotano/uso terapêutico , Saliva/química , Doença de Addison/metabolismo , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/tratamento farmacológico , Adulto , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Humanos , Hidrocortisona/uso terapêutico , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espectrometria de Massas em Tandem/métodos
19.
World J Surg ; 36(6): 1307-13, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22422171

RESUMO

BACKGROUND: Optimal treatment protocol to prevent symptomatic hypocalcemia following total thyroidectomy is still matter of debate. We prospectively evaluated the efficacy of a selective supplementation protocol based on both early postoperative intact parathyroid hormone (iPTH) and serum calcium levels. METHODS: Two hundred thirty consecutive patients were divided in three different groups of treatment according to iPTH levels 4 h after total thyroidectomy (4 h-iPTH) and serum calcium levels in the first postoperative day (1PO-Ca): group A (4 h-iPTH > 10 pg/ml, 1PO-Ca ≥ 8.5 mg/dl), no treatment; group B (4 h-iPTH > 10 pg/ml, 1PO-Ca < 8.5 mg/dl), oral calcium (OC) 3 g per day; and group C (4 h-iPTH ≤ 10 pg/ml), OC 3 g + calcitriol (VD) 1 µg per day. Development of biochemical and/or symptomatic hypocalcemia was evaluated. RESULTS: Fifty-nine patients (25.6%) had subnormal 4 h-iPTH levels (≤10 pg/ml) (group C). Among patients with normal 4 h-iPTH levels, 25 (10.9%) had subnormal 1PO-Ca (<8.5 mg/dl) (group B). The remaining 146 patients (63.5%) had normal 4 h-iPTH and 1PO-Ca levels (group A). One patient in group A, 2 in group B, and 18 in group C developed biochemical hypocalcemia. Only one patient in group C experienced major symptoms. Treatment was discontinued within 1 month in all the patients in group B. At a mean follow-up of 303 days, five patients in group C were still under supplementation treatment. CONCLUSION: The proposed supplementation protocol seems efficacious in preventing symptomatic hypocalcemia. It could allow a safe and early discharge of most patients, thus avoiding the constraints and the costs of routine supplementation.


Assuntos
Cálcio/sangue , Hipocalcemia/prevenção & controle , Hormônio Paratireóideo/sangue , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/prevenção & controle , Tireoidectomia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Calcitriol/uso terapêutico , Cálcio/uso terapêutico , Criança , Protocolos Clínicos , Suplementos Nutricionais , Feminino , Seguimentos , Humanos , Hipocalcemia/sangue , Hipocalcemia/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Estudos Prospectivos , Doenças da Glândula Tireoide/cirurgia , Resultado do Tratamento , Vitaminas/uso terapêutico , Adulto Jovem
20.
Clin Chem Lab Med ; 49(5): 851-3, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21361855

RESUMO

BACKGROUND: The poor comparability of growth hormone (GH) results obtained using commercially available methods, is partly due to standard preparations used in calibration. The system relies on the use of the International Reference Preparation (IRP) international standard (IS) 80/505, of human pituitary origin, containing all GH isoforms. Recently, a 22K recombinant GH isoform IRP IS 98/574 was commercialized. Our aim was to evaluate the influence of both calibrators on GH results. METHODS: GH concentration in 97 serum samples from children undergoing a growth hormone releasing hormone+arginine stimulation test was measured using Siemens IMMULITE electro-chemiluminescence method, calibrated with both IS 80/505 and IS 98/574 (GRH Growth hormone-Recombinant 98/574-kit). RESULTS: Comparison of our results obtained with the two sets of calibrators showed good correlation, although we found higher percentage variation (var%) than that stated by Siemens. The mean var% value was confirmed when all results were sub-divided into subgroups based on both high and low GH concentrations. CONCLUSIONS: Since the GH assay is influenced by a variety of binding proteins, isoforms and conversion factors, standardization of the assay is strongly required. In Italy, the Agenzia Italiana del Farmaco 39 note provides GH laboratory values which are useful for therapy. On the basis of our results, we therefore propose to adjourn these GH values in order to ensure better management of patients with GH-related disorders.


Assuntos
Hormônio do Crescimento Humano/sangue , Imunoensaio/normas , Calibragem , Criança , Hormônio do Crescimento Humano/imunologia , Humanos , Imunoensaio/instrumentação , Internacionalidade , Padrões de Referência
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