RESUMO
Giant congenital melanocytic nevi (GCMN) can be cosmetically significant and can lead to melanoma. There is no standard pharmacologic treatment for GCMN. We present the case of an 8-year-old female with kaposiform lymphangiomatosis caused by an NRAS mutation whose nevus spilus-type GCMN improved on oral selumetinib.
RESUMO
Atopic dermatitis (AD) is a common immune-medicated skin disease. Previous studies have explored the relationship between Human Leukocyte Antigen (HLA) allelic variation and AD with conflicting results. The aim was to examine HLA Class I genetic variation, specifically peptide binding groove variation, and associations with AD. A case-control study was designed to evaluate HLA class I allelic variation and binding pocket polymorphisms, using next generation sequencing on 464 subjects with AD and 388 without AD. Logistic regression was used to evaluate associations with AD by estimating odds ratios (95% confidence intervals). Significant associations were noted with susceptibility to AD (B*53:01) and protection from AD (A*01:01, A*02:01, B*07:02 and C*07:02). Evaluation of polymorphic residues in Class I binding pockets revealed six amino acid residues conferring protection against AD: A9F (HLA-A, position 9, phenylalanine) [pocket B/C], A97I [pocket C/E], A152V [pocket E], A156R [pocket D/E], B163E [pocket A] and C116S [pocket F]. These findings demonstrate that specific HLA class I components are associated with susceptibility or protection from AD. Individual amino acid residues are relevant to protection from AD and set the foundation for evaluating potential HLA Class I molecules in complex with peptides/antigens that may initiate or interfere with T-cell responses.
Assuntos
Dermatite Atópica/genética , Predisposição Genética para Doença , Variação Genética , Antígenos de Histocompatibilidade Classe I/genética , Alelos , Estudos de Casos e Controles , Dermatite Atópica/diagnóstico , Frequência do Gene , Estudos de Associação Genética , Genótipo , Antígenos de Histocompatibilidade Classe I/química , Humanos , Modelos Moleculares , Razão de Chances , Polimorfismo de Nucleotídeo Único , Conformação Proteica , Análise de Sequência de DNA , Relação Estrutura-AtividadeRESUMO
INTRODUCTION: Hip fracture usually occurs in older patients. These patients remain at risk for developing new medical complications even after discharge from the hospital. The objective of this study was to identify risk factors for hospital readmission 30 days after hip fracture and the prognosis of the readmitted patients. MATERIALS METHODS: A prospective, observational cohort study of 732 consecutive patients over 65 years surgically treated for hip fracture and discharged alive in 2010-2014 was conducted. The measurements were patient demographic characteristics, residential and discharge status, Katz Index, Merle D'aubigné Hip Score, Mini-Mental Test, comorbid conditions, Charlson Index, ASA group, type of fracture and repair, and postoperative complications. Patient characteristics were tested by bivariate and multivariate analyses. RESULTS: 8.3 % of patients were readmitted within 30 days (56.0 % of these within 2 weeks). Medical reasons were 13 times more frequent than surgical reasons. Diagnoses more prevalent for readmission were pulmonary disease, deep vein thrombosis, heart failure, and renal failure. Predictors of readmission were female gender (HR 1.9, 95 % CI 1.1-3.4), grade III-IV ASA (HR 2.1, 95 % CI 1.1-4.2), and pre-existing pulmonary disease (HR 5.3, 95 % CI 3.4-9.6). In-hospital mortality among readmitted patients was 22.9 %. In bivariate analyses, male gender, ASA III-IV, cognitive impairment, and more than two comorbidities were potential predictive factors for readmission, and in multivariate analysis only male gender and ASA III-IV. Mortality risk among readmitted patients was significantly higher compared to the in-hospital mortality in the overall cohort (OR 1.8, 95 % CI 1.5-2.3). CONCLUSIONS: Hospital readmissions after hip fracture were mainly due to medical complications and a fraction of these may be preventable. Readmission was associated with increased morbidity and mortality.
Assuntos
Fraturas do Quadril/cirurgia , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Incidência , Masculino , Complicações Pós-Operatórias/terapia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Fatores de TempoAssuntos
Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Animais , Proteínas de Drosophila , Feminino , Teste de Complementação Genética , Janus Quinases , Masculino , Camundongos , Peso Molecular , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fatores de TranscriçãoRESUMO
Previous developmental and reproductive toxicity studies in rats with losartan, a potent AT1-selective angiotensin II (AII) receptor antagonist, correlated maternal treatment during gestation day (GD) 15-20 with irreversible renal abnormalities in the F1 generation (Spence et al., '95a,b). Continued treatment through lactation was also associated with increases in pup mortality and decreases in pup body weights that persisted through weaning. The studies presented here were undertaken to quantify fetal and neonatal exposure to losartan when administered to the dam by oral gavage during early gestation, late gestation, and lactation. Following daily oral dosing of 135 mg/kg/day on GD6-15, fetal drug levels were negligible. However, losartan and its active metabolite, EXP3174 (L-158,641) were readily detectable in fetal plasma on GD 20 (estimated AUC values, 50.70 and 167.70 micrograms/hr/ml, respectively) and maternal milk during lactation (1.61 and 1.67 micrograms/ml, respectively). These studies suggest that the relative increased sensitivity of the fetus as compared to the neonate for losartan-induced renal lesions is related to the degree of exposure which is dependent on the time of administration (early gestation vs. late gestation/lactation) and the route of exposure (transplacental or through the milk). Furthermore, the maximum exposure to losartan and EXP3174 correlates with the ontogeny of the renin angiotensin system on approximately GD 17 and the critical period for losartan-induced renal lesions (GD15-20). The data support the hypothesis that the observed adverse fetal and neonatal effects are pharmacologically mediated, presumably through the lack of AT1 receptor stimulation.
Assuntos
Anti-Hipertensivos/toxicidade , Compostos de Bifenilo/toxicidade , Imidazóis/toxicidade , Tetrazóis/toxicidade , Animais , Anti-Hipertensivos/farmacocinética , Área Sob a Curva , Compostos de Bifenilo/farmacocinética , Feminino , Imidazóis/farmacocinética , Lactação , Losartan , Leite/química , Gravidez , Ratos , Ratos Sprague-Dawley , Tetrazóis/farmacocinéticaRESUMO
A rapid, sensitive and selective liquid chromatographic procedure was developed to quantitate the levels of a novel leukotriene D4 antagonist, MK-0571 (I), in biological samples. The method involves the addition of an internal standard, an analogue of I, and methanol to the biological matrix. Following centrifugation the supernatant is chromatographed isocratically on a C18 reversed-phase column and the acids are detected with an ultraviolet detector. The sensitivity of the method is such that 50 ng of drug can be quantitated per aliquot of sample. Assays were linear over a 0.06-40.0 micrograms range and exhibited a recovery of 100.5 +/- 7.0% (mean +/- S.D.) over this range. This procedure was utilized to monitor plasma, liver and urinary levels of I in chronic and acute toxicity studies in several animal species.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Fígado/química , Propionatos/sangue , Quinolinas/sangue , SRS-A/antagonistas & inibidores , Animais , Cromatografia Líquida de Alta Pressão/instrumentação , Feminino , Macaca mulatta , Masculino , Propionatos/química , Propionatos/urina , Quinolinas/química , Quinolinas/urina , Ratos , Ratos Endogâmicos , Raios UltravioletaRESUMO
Two cases of patients suffering from a cystic lymphangioma of the mediastinum are presented. The literature is reviewed and the surgical and pathological findings are commented.