RESUMO
To document the magnetic resonance imaging (MRI) features of diffuse large B-cell lymphoma (DLBCL) in Waldeyer's ring (WR) and the sinonasal (SN) region, and to identify any differences between lymphatic and extra-lymphatic DLBCLs, and predictors of disease beyond the neck. Primary, nodal, and multifocal sites on head and neck MRI were compared between 31 WR and 15 SN DLBCL, and between 27 patients with disease confined to the head and neck and 16 patients with disease beyond the neck, using logistic regression. Compared to SN, WR DLBCLs had significantly smaller primary tumour volumes (p = 0.009), less deep invasion (p = 0.001), and more nodal disease (p = 0.016). Tumour site (WR vs. SN) was an independent predictor of deep invasion (p = 0.007). Nodal and multifocal diseases were predictors of disease beyond the neck (p = 0.027 and 0.011, respectively). Lymphatic WR DLBCLs were less locally aggressive but had greater propensity to nodal spread than extra-lymphatic SN DLBCLs. Nodal and multifocal diseases predicted disease beyond the neck.
Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Imageamento por Ressonância Magnética , Neoplasias Nasais/diagnóstico por imagem , Neoplasias Tonsilares/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Estudos RetrospectivosRESUMO
We present a case illustrating the rare complication of acute generalized thyroid swelling shortly after sonographic-guided fine needle aspiration of a thyroid nodule. Ultrasound revealed the presence of characteristic linear hypoechoic avascular areas interspersed throughout the gland suggestive of edema. The patient was treated conservatively, with near complete normalization of the thyroid within 24 hours. Recognition of this potential complication is important, as the rapid onset of diffuse thyroid enlargement is often alarming but typically has a transient and self-limiting course. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:426-429, 2017.
Assuntos
Edema/diagnóstico por imagem , Edema/etiologia , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Ultrassonografia/métodos , Doença Aguda , Idoso , Biópsia por Agulha Fina/efeitos adversos , Feminino , HumanosRESUMO
Anorectal malformations (ARMs, congenital obstruction of the anal opening) are among the most common birth defects requiring surgical treatment (2-5/10 000 live-births) and carry significant chronic morbidity. ARMs present either as isolated or as part of the phenotypic spectrum of some chromosomal abnormalities or monogenic syndromes. The etiology is unknown. To assess the genetic contribution to ARMs, we investigated single-nucleotide polymorphisms and copy number variations (CNVs) at genome-wide scale. A total of 363 Han Chinese sporadic ARM patients and 4006 Han Chinese controls were included. Overall, we detected a 1.3-fold significant excess of rare CNVs in patients. Stratification of patients by presence/absence of other congenital anomalies showed that while syndromic ARM patients carried significantly longer rare duplications than controls (P = 0.049), non-syndromic patients were enriched with both rare deletions and duplications when compared with controls (P = 0.00031). Twelve chromosomal aberrations and 114 rare CNVs were observed in patients but not in 868 controls nor 11 943 healthy individuals from the Database of Genomic Variants. Importantly, these aberrations were observed in isolated ARM patients. Gene-based analysis revealed 79 genes interfered by CNVs in patients only. In particular, we identified a de novo DKK4 duplication. DKK4 is a member of the WNT signaling pathway which is involved in the development of the anorectal region. In mice, Wnt disruption results in ARMs. Our data suggest a role for rare CNVs not only in syndromic but also in isolated ARM patients and provide a list of plausible candidate genes for the disorder.
Assuntos
Anus Imperfurado/genética , Anus Imperfurado/fisiopatologia , Variações do Número de Cópias de DNA , Duplicação Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Animais , Malformações Anorretais , Povo Asiático , Aberrações Cromossômicas , Feminino , Dosagem de Genes , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fenótipo , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Via de Sinalização WntRESUMO
Hirschsprung disease (HSCR, aganglionic megacolon) is a complex genetic disorder of the enteric nervous system (ENS) characterized by the absence of enteric neurons along a variable length of the intestine. While rare variants (RVs) in the coding sequence (CDS) of several genes involved in ENS development lead to disease, the association of common variants (CVs) with HSCR has only been reported for RET (the major HSCR gene) and NRG1. Importantly, RVs in the CDS of these two genes are also associated with the disorder. To assess independent and joint effects between the different types of RET and NRG1 variants identified in HSCR patients, we used 254 Chinese sporadic HSCR patients and 143 ethnically matched controls for whom the RET and/or NRG1 variants genotypes (rare and common) were available. Four genetic risk factors were defined and interaction effects were modeled using conditional logistic regression analyses and pair-wise Kendall correlations. Our analysis revealed a joint effect of RET CVs with RET RVs, NRG1 CVs or NRG1 RVs. To assess whether the genetic interaction translated into functional interaction, mouse neural crest cells (NCCs; enteric neuron precursors) isolated from embryonic guts were treated with NRG1 (ErbB2 ligand) or/and GDNF (Ret ligand) and monitored during the subsequent neural differentiation process. Nrg1 inhibited the Gdnf-induced neuronal differentiation and Gdnf negatively regulated Nrg1-signaling by down-regulating the expression of its receptor, ErbB2. This preliminary data suggest that the balance neurogenesis/gliogenesis is critical for ENS development.
Assuntos
Variação Genética/genética , Doença de Hirschsprung/genética , Neuregulina-1/genética , Proteínas Proto-Oncogênicas c-ret/genética , Animais , Estudos de Casos e Controles , Células Cultivadas , China , Feminino , Genômica , Genótipo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Projeto HapMap , Doença de Hirschsprung/metabolismo , Humanos , Intestinos/citologia , Intestinos/inervação , Desequilíbrio de Ligação , Masculino , Camundongos , Mutação , Crista Neural/citologia , Neuregulina-1/metabolismo , Fenótipo , Proteínas Proto-Oncogênicas c-ret/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Fatores de Risco , TransgenesRESUMO
Hirschsprung disease (HSCR, congenital colon aganglionosis) is a relatively common complex genetic condition caused by abnormal development of the enteric nervous system (ENS). Through a recent genome-wide association study conducted on Chinese HSCR patients, we identified a new HSCR contributing locus, neuregulin 1 (NRG1; 8p12), a gene known to be involved in the development of the ENS. As genes in which disease-associated common variants are found are to be considered as candidates for the search of deleterious rare variants (RVs) in the coding sequences, we sequenced the NRG1 exons of 358 sporadic HSCR patients and 333 controls. We identified a total of 13 different heterozygous RVs including 8 non-synonymous (A28G, E134K, V266L, H347Y, P356L, V486M, A511T, P608A) and 3 synonymous amino acid substitutions (P24P, T169T, L483L), a frameshift (E239fsX10), and a c.503-4insT insertion. Functional analysis of the most conserved non-synonymous substitutions, H347Y and P356L, showed uneven intracellular distribution and aberrant expression of the mutant proteins. Except for T169T and V486M, all variants were exclusive to HSCR patients. Overall, there was a statistically significant over-representation of NRG1 RVs in HSCR patients (p = 0.008). We show here that not only common, but also rare variants of the NRG1 gene contribute to HSCR. This strengthens the role of NRG1.
Assuntos
Doença de Hirschsprung/genética , Mutação/genética , Neuregulina-1/genética , Animais , Células COS , Estudos de Casos e Controles , Chlorocebus aethiops , Análise Mutacional de DNA , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Immunoblotting , Técnicas Imunoenzimáticas , MasculinoRESUMO
BACKGROUND: Limbic encephalitis is characterized by rapid onset of working memory deficit, mood changes, and often seizures. The condition has a strong paraneoplastic association, but not all cases are invariably due to tumors. CASE PRESENTATION: We present a case of limbic encephalitis in a Chinese patient who initially presented to our hospital with optic neuritis and no other neurological symptoms. The diagnosis was made radiologically, and cognitive and neurological symptoms did not occur until 5 months later. Extensive investigations for autoimmune, infective, and neoplastic causes were all negative. A working diagnosis of paraneoplastic neurological syndrome was made, and the patient is being managed with high-dose steroid therapy according to the Optic Neuritis Treatment Trial protocol during relapses, as well as with tumor surveillance. CONCLUSIONS: This case highlights ocular symptoms as important clues for diagnosing neurological diseases, as well as autoimmune encephalitis as an important differential diagnosis in the management of "idiopathic" optic neuritis in the Chinese population.
Assuntos
Encefalite Límbica/complicações , Encefalite Límbica/diagnóstico por imagem , Neurite Óptica/diagnóstico por imagem , Neurite Óptica/etiologia , Adulto , Encéfalo/diagnóstico por imagem , China , Diagnóstico Diferencial , Feminino , Glucocorticoides/uso terapêutico , Humanos , Encefalite Límbica/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Metilprednisolona/uso terapêutico , Neurite Óptica/tratamento farmacológicoAssuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Tumor Rabdoide/diagnóstico por imagem , Tumor Rabdoide/patologia , Teratoma/diagnóstico por imagem , Teratoma/patologia , Adolescente , Encéfalo/cirurgia , Neoplasias Encefálicas/cirurgia , Diagnóstico Diferencial , Humanos , Masculino , Tumor Rabdoide/cirurgia , Teratoma/cirurgiaRESUMO
The primary pathology of Hirschsprung's disease (HSCR, colon aganglionosis) is the absence of ganglia in variable lengths of the hindgut, resulting in functional obstruction. HSCR is attributed to a failure of migration of the enteric ganglion precursors along the developing gut. RET is a key regulator of the development of the enteric nervous system (ENS) and the major HSCR-causing gene. Yet the reduced penetrance of RET DNA HSCR-associated variants together with the phenotypic variability suggest the involvement of additional genes in the disease. Through a genome-wide association study, we uncovered a â¼350 kb HSCR-associated region encompassing part of the neuregulin-1 gene (NRG1). To identify the causal NRG1 variants contributing to HSCR, we genotyped 243 SNPs variants on 343 ethnic Chinese HSCR patients and 359 controls. Genotype analysis coupled with imputation narrowed down the HSCR-associated region to 21 kb, with four of the most associated SNPs (rs10088313, rs10094655, rs4624987, and rs3884552) mapping to the NRG1 promoter. We investigated whether there was correlation between the genotype at the rs10088313 locus and the amount of NRG1 expressed in human gut tissues (40 patients and 21 controls) and found differences in expression as a function of genotype. We also found significant differences in NRG1 expression levels between diseased and control individuals bearing the same rs10088313 risk genotype. This indicates that the effects of NRG1 common variants are likely to depend on other alleles or epigenetic factors present in the patients and would account for the variability in the genetic predisposition to HSCR.
Assuntos
Mapeamento Cromossômico , Loci Gênicos , Doença de Hirschsprung/genética , Neuregulina-1/genética , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Epigenômica , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
This study aimed to examine the reliability and validity of the Euthanasia Attitude Scale (EAS) in Hong Kong medical doctors. A total of 107 medical doctors (61.7% men) participated in a survey at clinical settings in 2008. The 21-item EAS was used to assess their attitudes toward euthanasia. The mean (standard deviation) and median of the EAS were 63.60 (60.31) and 63.00. Total EAS scores correlated well with ''Ethical Considerations,'' ''Practical Considerations,'' and ''Treasuring Life'' (Spearman rho =.37-.96, P < .001) but not ''Naturalistic Beliefs.'' The construct validity of the 3-factor model was appropriate (Kaiser-Meyer-Olkin [KMO] value = 0.90) and showed high internal consistency (Cronbach alpha =.79-.92). Euthanasia Attitude Scale may be a reliable and valid measure for assessing the attitudes toward euthanasia in medical professionals.
Assuntos
Atitude do Pessoal de Saúde , Eutanásia , Médicos/estatística & dados numéricos , Padrões de Prática Médica/normas , Inquéritos e Questionários/normas , Adulto , Atitude Frente a Morte , Características Culturais , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) is one of the most common gastrointestinal obstructions in the infancy requiring surgery. Reduced expression of neuronal nitric oxide synthase (nNOS), which plays an important role in the regulation of the human pyloric muscle, is thought to underlie IHPS. The role of nNOS in IHPS has been supported by the genetic association of a functional regulatory nNOS polymorphism (-84G>A) with IHPS in whites. We reasoned that the corroboration of this association in a population of different ethnic origin would prompt follow-up studies and further investigation of the IHPS pathology at molecular level. Thus, we attempted to reproduce the original findings in a Chinese population of comparable size in what would be the first genetic study on IHPS conducted in Chinese. METHODS: nNOS -84G>A genotypes were analyzed in 56 patients and 86 controls by polymerase chain reaction and DNA sequencing. Logistic regression was used to compute odds ratios. RESULTS: Our study could not corroborate the association previously reported. Although the frequency of the IHPS-associated allele (-84A) in controls (0.205) was similar to that reported for white controls, there was a dramatic difference in -84A frequencies between white and Chinese patients (0.198). Similarly, there was no difference in the nNOS -84G>A genotype distribution between patients and controls, even when the GA and AA genotypes were combined to compare GG genotype (odds ratio, 1.01; 95% confidence interval, 0.47-2.19). CONCLUSIONS: Failure to replicate the initial finding does not detract from its validity, because genetic effects may differ across populations. Differences across populations in linkage disequilibrium and/or allele frequencies may contribute to this lack of replication. The role nNOS in IHPS awaits further investigation.