RESUMO
Although glufosinate ammonium herbicides are considered safe when used properly, ingestion of the undiluted form can cause grave outcomes. Recently, we treated a 34-yr-old man who ingested glufosinate ammonium herbicide. In the course of treatment, the patient developed apnea, mental deterioration, and sixth cranial nerve palsy; he has since been discharged with full recovery after intensive care. This case report describes the clinical features of glufosinate intoxication with a focus on sixth cranial nerve palsy. Our observation suggests that neurologic manifestations after ingestion of a "low-grade toxicity herbicide" are variable and more complex than that was previously considered.
Assuntos
Doenças do Nervo Abducente/induzido quimicamente , Aminobutiratos/intoxicação , Herbicidas/intoxicação , Doenças do Nervo Abducente/tratamento farmacológico , Adulto , Inibidores Enzimáticos/intoxicação , Humanos , Masculino , Convulsões/induzido quimicamente , Tensoativos/intoxicação , Inconsciência/induzido quimicamenteRESUMO
Dutasteride, a dual inhibitor of both type I and II 5α-reductases, is used to treat male pattern hair loss (MPHL). However, patient response to dutasteride varies in each individual, the cause of which is yet to be identified. To identify genetic variants associated with response to dutasteride treatment for MPHL, a total of 42 men with moderate MPHL who had been treated with dutasteride for 6 months were genotyped and analysed by quantitative linear regression, case-control association tests, and Fisher's exact test. The synonymous single nucleotide polymorphism (SNP) rs72623193 in DHRS9 was most significantly associated with response to dutasteride, followed by the non-synonymous SNP rs2241057 in CYP26B1. Additionally, variants in ESR1, SRD5A1, CYP19A1, and RXRG are suggested to be associated with response to dutasteride. Cumulative effect and interaction among these SNPs were presented in both additive and non-additive models.
Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Alopecia/tratamento farmacológico , Alopecia/genética , Dutasterida/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Adulto , Estudos de Casos e Controles , Cabelo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Context: Thyroid nodules are very common, and 7% to 15% of them are diagnosed as thyroid cancer. However, the inherited genetic risk factors for thyroid nodules and their associations with thyroid cancer remain unknown. Objective: To identify the genetic variants associated with susceptibility to thyroid nodules in comparison with thyroid cancer. Design and Setting: We performed a three-stage genome-wide association study for thyroid nodules. The discovery stage involved a genome-wide scan of 811 subjects with thyroid nodules and 691 subjects with a normal thyroid from a population-based cohort. Replication studies were conducted in an additional 1981 cases and 3100 controls from the participants of a health checkup. We also performed expression quantitative trait loci analysis of public data. Results: The most robust association was observed in TRPM3 (rs4745021) in the joint analysis (OR, 1.26; P = 6.12 × 10-8) and meta-analysis (OR, 1.28; P = 2.11 × 10-8). Signals at MBIP/NKX2-1 were replicated but did not reach genome-wide significance in the joint analysis (rs2415317, P = 4.62 × 10-5; rs944289, P = 8.68 × 10-5). The expression quantitative trait loci analysis showed that TRPM3 expression was associated with the rs4745021 genotype in thyroid tissues. Conclusions: To the best of our knowledge, we have performed the first genome-wide association study of thyroid nodules and identified a susceptibility locus associated with thyroid nodules, suggesting that thyroid nodules have a genetic predisposition distinct from that of thyroid cancer.
Assuntos
Biomarcadores Tumorais/genética , Predisposição Genética para Doença , Canais de Cátion TRPM/genética , Neoplasias da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/genética , Adulto , Estudos de Coortes , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prevalência , Locos de Características Quantitativas/genética , República da Coreia/epidemiologia , Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/epidemiologia , Fator Nuclear 1 de Tireoide/genéticaRESUMO
Thyroid cancer is the most common cancer in Korea. Several susceptibility loci of differentiated thyroid cancer (DTC) were identified by previous genome-wide association studies (GWASs) in Europeans only. Here we conducted a GWAS and a replication study in Koreans using a total of 1,085 DTC cases and 8,884 controls, and validated these results using expression quantitative trait loci (eQTL) analysis and clinical phenotypes. The most robust associations were observed in the NRG1 gene (rs6996585, P=1.08 × 10-10) and this SNP was also associated with NRG1 expression in thyroid tissues. In addition, we confirmed three previously reported loci (FOXE1, NKX2-1 and DIRC3) and identified seven novel susceptibility loci (VAV3, PCNXL2, INSR, MRSB3, FHIT, SEPT11 and SLC24A6) associated with DTC. Furthermore, we identified specific variants of DTC that have different effects according to cancer type or ethnicity. Our findings provide deeper insight into the genetic contribution to thyroid cancer in different populations.