RESUMO
A DPD deficiency should be considered in case of severe toxicity even in the absence of common risk variants in DPYD.
Assuntos
Antimetabólitos Antineoplásicos , Capecitabina , Deficiência da Di-Hidropirimidina Desidrogenase , Di-Hidrouracila Desidrogenase (NADP) , Humanos , Deficiência da Di-Hidropirimidina Desidrogenase/genética , Capecitabina/efeitos adversos , Di-Hidrouracila Desidrogenase (NADP)/genética , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Masculino , Feminino , Evolução Fatal , Pessoa de Meia-IdadeAssuntos
Cromatografia Líquida/métodos , Melatonina/biossíntese , Radioimunoensaio/métodos , Saliva/metabolismo , Espectrometria de Massas em Tandem/métodos , Calibragem , Cromatografia Líquida/normas , Humanos , Laboratórios/normas , Melatonina/análise , Radioimunoensaio/normas , Análise de Regressão , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/normasRESUMO
OBJECTIVE: The aim of this study was to develop a serum human chorionic gonadotropin (hCG) normogram for both uneventful complete and partial hydatidiform moles in the first-trimester ultrasound era. METHODS: An hCG normogram for both complete and partial hydatidiform moles was constructed, based on 639 patients with uneventful serum hCG regression after evacuation between 1990 and 2014. Serum hCG was measured by an in-house-developed radioimmunoassay, detecting both intact hCG and free ß-subunit. It has been in use for all serum measurements sent to the Dutch Central Registry for Hydatidiform Moles since 1977. RESULTS: Since introduction of routine first-trimester ultrasonography, lower pre-evacuation and follow-up serum hCG concentrations were observed. When compared with complete hydatidiform moles, patients with a partial hydatidiform mole had significantly lower pre-evacuation serum hCG concentration (median, 4400 and 875 ng/mL, respectively; P < 0.001) and earlier hCG normalization (median, 7 and 6 weeks, respectively; P < 0.001) but higher gestational age (mean, 11.5 and 13.0 weeks, respectively; P < 0.001). For both complete and partial hydatidiform moles, 95% of patients reached normal serum hCG concentrations within 14 weeks after evacuation. CONCLUSIONS: A normogram for the detection of gestational trophoblastic neoplasia was developed for complete and partial hydatidiform moles. Although interesting from a scientific perspective, the small divergence in hCG regression between complete and partial hydatidiform moles will be of little importance in clinical practice, as actual differences in regression will encompass only days. To promote clarity and unity in daily practice, we therefore propose a combined normogram to be used as a reference guideline for follow-up after evacuation of a hydatidiform mole. This normogram will be compliant with patients in today's clinical practice.
Assuntos
Gonadotropina Coriônica/sangue , Doença Trofoblástica Gestacional/sangue , Adulto , Estudos de Coortes , Feminino , Doença Trofoblástica Gestacional/diagnóstico por imagem , Humanos , Mola Hidatiforme/sangue , Mola Hidatiforme/diagnóstico por imagem , Gravidez , Valores de Referência , Ultrassonografia Pré-NatalRESUMO
A 36-year old female patient who had had iron deficiency anaemia since her childhood showed no clear response to oral iron treatment. Elevated serum hepcidin levels were found after excluding other causes of iron deficiency. This is in contrast to what is expected in iron deficiency anaemia and indicates a primary defect in hepcidin regulation. Indeed, in the search for a defect in genes coding for hepcidin-regulating proteins the patient was found to be compound heterozygous for two different mutations in the TMPRSS6 gene. This leads to a dysfunctional matriptase-2 protein for which the gene codes. Consequently, liver cells cannot inhibit hepcidin production in the presence of low serum iron levels. High hepcidin levels result in less iron being absorbed from the bowel than is necessary for erythropoiesis. Therefore, patients with matriptase-2 deficiency respond poorly to oral iron treatment and have to be treated with intravenous iron.
Assuntos
Anemia Ferropriva/enzimologia , Anemia Ferropriva/genética , Peptídeos Catiônicos Antimicrobianos/sangue , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Adulto , Anemia Ferropriva/tratamento farmacológico , Feminino , Hepcidinas , Humanos , Ferro/uso terapêutico , Mutação/genética , Linhagem , Falha de TratamentoRESUMO
The autoantigenic polymyositis/scleroderma (PM/Scl) complex was recently shown to be the human homologue of the yeast exosome, which is an RNA-processing complex. Our aim was to assess whether, in addition to targeting the known autoantigens PM/Scl-100 and PM/Scl-75, autoantibodies also target recently identified components of the PM/Scl complex. The prevalence of autoantibodies directed to six novel human exosome components (hRrp4p, hRrp40p, hRrp41p, hRrp42p, hRrp46p, hCsl4p) was determined in sera from patients with idiopathic inflammatory myopathy (n = 48), scleroderma (n = 11), or the PM/Scl overlap syndrome (n = 10). The sera were analyzed by enzyme-linked immunosorbent assays and western blotting using the affinity-purified recombinant proteins. Our results show that each human exosome component is recognized by autoantibodies. The hRrp4p and hRrp42p components were most frequently targeted. The presence of autoantibodies directed to the novel components of the human exosome was correlated with the presence of the anti-PM/Scl-100 autoantibody in the sera of patients with idiopathic inflammatory myopathy (IIM), as was previously found for the anti-PM/Scl-75 autoantibody. Other clear associations between autoantibody activities were not found. These results further support the conception that the autoimmune response may initially be directed to PM/Scl-100, whereas intermolecular epitope spreading may have caused the autoantibody response directed to the associated components.
