RESUMO
BACKGROUND: Interferon-alpha (IFNα)-induced thyroid dysfunction occurs in up to 20% of patients undergoing therapy for hepatitis C. The diversity of thyroid disease presentations suggests that several different pathological mechanisms are involved, such as autoimmunity and direct toxicity. Elucidating the relationships between risk factors and disease phenotype provides insight into the mechanisms of disease pathophysiology. METHODS: We studied 869 euthyroid patients from the ACHIEVE 2/3 trial, a randomized international clinical trial comparing pegylated-IFNα2a weekly or albumin-IFNα2b every 2 weeks for up to 24 weeks in patients with hepatitis C, genotype 2 or 3, from 136 centers. The study population was 60% male and 55% white. Serum thyrotropin (TSH) and free thyroxine were measured before therapy, monthly during treatment from week 8, and at 4- and 12-week follow-up visits. RESULTS: Overall, 181 (20.8%) participants had at least one abnormal TSH during the study. Low TSH occurred in 71 (8.2%), of whom 30 (3.5%) had a suppressed TSH below 0.1 mU/L. Hypothyroidism occurred in 53 patients (6.1%), with peak TSH above 10 mU/L in 12 patients (1.4%). Fifty-seven patients had a biphasic thyroiditis (6.6%), with extreme values for the nadir and/or peak TSH in all but one. Medical therapy was given to one thyrotoxic patient, four hypothyroid patients, and 26 biphasic thyroiditis patients. Multivariate logistic regression analysis demonstrated that biphasic thyroiditis is associated with being female and higher pretreatment serum TSH, whereas being Asian or a current smoker decreased the risk of thyroiditis. Hypo- and hyperthyroidism are most strongly predicted by the pretreatment TSH. CONCLUSIONS: Biphasic thyroiditis accounted for the majority (58%) of clinically relevant IFNα-induced thyroid dysfunction. We confirmed our recent findings in a related cohort that female sex is a risk factor for thyroiditis but not hypothyroidism. Further, in this large multiethnic study, the risk of thyroiditis is dramatically increased, specifically for white women. Smoking was found to be protective of thyroiditis. These results support closer monitoring of women and those with a serum TSH at the extremes of the normal range during therapy so that prompt intervention can mitigate the consequences of thyroid dysfunction associated with IFNα treatment.
Assuntos
Antivirais/efeitos adversos , Hepatite C/tratamento farmacológico , Hipotireoidismo/induzido quimicamente , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Grupos Raciais , Albumina Sérica/efeitos adversos , Fumar/efeitos adversos , Tireoidite/induzido quimicamente , Tireotropina/sangue , Adulto , Ásia/epidemiologia , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Europa (Continente)/epidemiologia , Feminino , Hepatite C/sangue , Hepatite C/diagnóstico , Hepatite C/etnologia , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/etnologia , Hipotireoidismo/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , América do Norte/epidemiologia , Razão de Chances , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Fatores de Risco , Albumina Sérica Humana , Fatores Sexuais , América do Sul/epidemiologia , Tireoidite/sangue , Tireoidite/etnologia , Tireoidite/terapia , Tiroxina/sangue , Fatores de Tempo , Resultado do TratamentoRESUMO
Crotalus durissus terrificus venom and its main component, crotoxin (CTX), have the ability to down-modulate the immune system. Certain mechanisms mediated by cells and soluble factors of the immune system are responsible for the elimination of pathogenic molecules to ensure the specific protection against subsequent antigen contact. Accordingly, we evaluated the immunomodulatory effects of CTX on the immune response of mice that had been previously primed by immunisation with human serum albumin (HSA). CTX inoculation after HSA immunisation, along with complete Freund's adjuvant (CFA) or Aluminium hydroxide (Alum) immunisation, was able to suppress anti-HSA IgG1 and IgG2a antibody production. We showed that the inhibitory effects of this toxin are not mediated by necrosis or apoptosis of any lymphoid cell population. Lower proliferation of T lymphocytes from mice immunised with HSA/CFA or HSA/Alum that received the toxin was observed in comparison to the mice that were only immunised. In conclusion, CTX is able to exert potent inhibitory effects on humoral and cellular responses induced by HSA immunisation, even when injected after an innate immune response has been initiated.
Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Venenos de Crotalídeos/imunologia , Crotoxina/toxicidade , Albumina Sérica/efeitos adversos , Imunidade Adaptativa/imunologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Necrose/induzido quimicamente , Albumina Sérica/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologiaRESUMO
O presente estudo estabelece valores de referência dos teores séricos de proteínas totais, albumina, AST e GGT em ovinos da raça santa Inês e avalia a interferência de fatores sexuais e etários sobre estas variáveis. Foram colhidas amostras de sangue de 161 ovelhas. O resultado encontrado para os valores padrões séricos foram 5,86 +0,96 g/dL para proteínas totais, 2,33+0,43 g/dL para albumina, 63,25+27,52 U/L para AST e 28,45+14,53 U/L para GGT. A análise dos resultados permite afirmar que os valores referentes à concentração sérica de albumina e à atividade sérica de AST sofrem influência de fatores sexuais e etários, e os valores referentes à atividade sérica de GGT sofrem influência somente de fatores etários. Não foram encontradas influências dos fatores sexuais e etários para os outros parâmetros estudados.(AU)
This work establishes reference values for serum protein and albumin and serum activities of AST and GGT of Santa Inês sheep and evaluates the sexual and age influence on these values. Blood samples were collected from 161 clinically healthy sheep. The results allowed to establish the following reference values 5,86 + 0,96 g/dL (P>0,05)for serum protein, 2,33+0,43 g/dL (P>0,05) for albumin, 63,25+27,52 U/L (P>0,05) for AST and 28,45+14,53 U/L (P>0,05)for GGT. The results analysis also allowed concluding that age and sex influence on albumin serum concentrations and AST serum activity and that GGT serum activity suffer age influence.(AU)
Assuntos
Animais , Fatores Sexuais , Fatores Etários , Albumina Sérica/efeitos adversos , Albumina Sérica/análise , Proteínas Sanguíneas/análise , Aspartato Aminotransferases/efeitos adversos , gama-Glutamiltransferase/efeitos adversos , OvinosRESUMO
As controvérsias em torno da indicação terapêutica da albumina humana (AH) e o impacto nos custos hospitalares pelo uso irracional do produto, motivaram nas três últimas décadas, a realização de estudos a respeito do problema em diversos países. No Brasil, as iniciativas de racionalização de uso da AH são escassas e pouco difundidas. Esta tese é apresentada em três artigos que abordam os aspectos clínicos e epidemiológicos do uso da AH em hospitais do Rio de Janeiro, utilizando dados primários e secundários...
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Revisão de Uso de Medicamentos , Pacientes Internados , Albumina Sérica , Uso de Medicamentos/estatística & dados numéricos , Albumina Sérica/efeitos adversos , Pesquisa sobre Serviços de Saúde , Brasil , Sistemas de Informação Hospitalar , Prontuários Médicos , Distúrbios Nutricionais , Prescrições de Medicamentos , Estudos Retrospectivos , RiscoRESUMO
Blood and its products are valuable therapeutic resources for the pediatrician who care for newborns with severe illnesses. The use of blood and its products requires for the hospital personnel working at neonatal care units to be precise and up to date on the indications and complications of total blood, the globular package, albumin, plasma, the concentration of granulocytes, platelets and immunoglobulins for intravenous use. This review gathers, on the one hand, accumulated experiences by the members of the Commission of Blood and its Products from the Pediatric Hospital of the National Medical Center and on the other hand, a selection of the more important concepts which have been judged so by the authors and expressed in the current medical literature.