Assuntos
Azitromicina/administração & dosagem , Anormalidades Cardiovasculares , Transtornos de Deglutição , Infecções por Mycoplasma , Prednisona/administração & dosagem , Artéria Subclávia/anormalidades , Anel Vascular , Antibacterianos/administração & dosagem , Anormalidades Cardiovasculares/diagnóstico , Anormalidades Cardiovasculares/fisiopatologia , Criança , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/terapia , Diagnóstico Diferencial , Ecocardiografia/métodos , Endoscopia do Sistema Digestório/métodos , Esofagite/diagnóstico , Esofagite/etiologia , Esofagite/fisiopatologia , Esofagite/terapia , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Glucocorticoides/administração & dosagem , Humanos , Masculino , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/fisiopatologia , Mycoplasma pneumoniae/isolamento & purificação , Recidiva , Artéria Subclávia/fisiopatologia , Resultado do Tratamento , Anel Vascular/diagnóstico , Anel Vascular/fisiopatologiaAssuntos
Fígado/patologia , Doenças de Niemann-Pick/diagnóstico , Transaminases/sangue , Dor Abdominal/etiologia , Biópsia , Índice de Massa Corporal , Criança , Diagnóstico Diferencial , Humanos , Lipídeos/sangue , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Doenças de Niemann-Pick/complicações , Obesidade Infantil/sangue , Esplenomegalia/diagnóstico por imagemRESUMO
Ulcerative colitis is associated with an increased risk of thromboembolic phenomena. Thrombotic storm defined by the development of multiple thrombi in multiple locations within a short period of time is a rare condition that is potentially life threatening. We present a 14-year-old adolescent boy with an ulcerative colitis flare complicated by Budd-Chiari syndrome and thrombotic storm.
RESUMO
Bile acid (BA) biosynthesis is tightly controlled by intrahepatic negative feedback signaling elicited by BA binding to farnesoid X receptor (FXR) and also by enterohepatic communication involving ileal BA reabsorption and FGF15/19 secretion. However, how these pathways are coordinated is poorly understood. We show here that nonreceptor tyrosine phosphatase Shp2 is a critical player that couples and regulates the intrahepatic and enterohepatic signals for repression of BA synthesis. Ablating Shp2 in hepatocytes suppressed signal relay from FGFR4, receptor for FGF15/19, and attenuated BA activation of FXR signaling, resulting in elevation of systemic BA levels and chronic hepatobiliary disorders in mice. Acting immediately downstream of FGFR4, Shp2 associates with FRS2α and promotes the receptor activation and signal relay to several pathways. These results elucidate a molecular mechanism for the control of BA homeostasis by Shp2 through the orchestration of multiple signals in hepatocytes.
Assuntos
Ácidos e Sais Biliares/biossíntese , Fígado/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Transdução de Sinais , Animais , Ductos Biliares/lesões , Linhagem Celular , Colesterol 7-alfa-Hidroxilase/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Fígado/patologia , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Proteína Tirosina Fosfatase não Receptora Tipo 11/deficiência , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Regulação para CimaRESUMO
OBJECTIVE: To determine the effectiveness of developmental screening on the identification of developmental delays, early intervention (EI) referrals, and EI eligibility. METHODS: This randomized controlled, parallel-group trial was conducted from December 2008 to June 2010 in 4 urban pediatric practices. Children were eligible if they were <30 months old, term, without congenital malformations or genetic syndromes, not in foster care, and not enrolled in EI. Children were randomized to receive 1 of the following: (1) developmental screening using Ages and Stages Questionnaire-II (ASQ-II and Modified Checklist for Autism in Toddlers (M-CHAT) with office staff assistance, (2) developmental screening using ASQ-II and M-CHAT without office staff assistance, or (3) developmental surveillance using age-appropriate milestones at well visits. Outcomes were assessed using an intention-to-treat analysis. RESULTS: A total of 2103 children were enrolled. Most were African-American with family incomes less than $30,000. Children in either screening arm were more likely to be identified with delays (23.0% and 26.8% vs 13.0%; P < .001), referred to EI (19.9% and 17.5% vs 10.2%; P < .001), and eligible for EI services (7.0% and 5.3% vs 3.0%; P < .001) than children in the surveillance arm. Children in the screening arms incurred a shorter time to identification, EI referral, and EI evaluation than children in the surveillance arm. CONCLUSIONS: Children who participated in a developmental screening program were more likely to be identified with developmental delays, referred to EI, and eligible for EI services in a timelier fashion than children who received surveillance alone. These results support policies endorsing developmental screening.
Assuntos
Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/epidemiologia , Programas de Rastreamento/métodos , População Urbana , Adolescente , Criança , Pré-Escolar , Deficiências do Desenvolvimento/terapia , Feminino , Humanos , Lactente , Masculino , Resultado do TratamentoRESUMO
PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating cellular responses to hormones and cytokines. Against original prediction as tumor suppressor for tyrosine phosphatases, PTPN11 was first identified as a proto-oncogene because activating mutations of this gene are associated with leukemogenesis. However, most recent experimental data suggest PTPN11/Shp2 acting as a tumor suppressor in hepatocarcinogenesis. This review focuses on the tumor-promoting or suppressing roles of the gene PTPN11/Shp2 in different cell types.
Assuntos
Carcinoma Hepatocelular/genética , Transformação Celular Neoplásica/genética , Neoplasias Hepáticas/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Animais , Carcinoma Hepatocelular/enzimologia , Predisposição Genética para Doença , Humanos , Neoplasias Hepáticas/enzimologia , Camundongos , Camundongos Knockout , Mutação , Proto-Oncogene MasRESUMO
BACKGROUND: Performance of specialty referrals is coming under scrutiny, but a lack of identifiable measures impedes measurement efforts. The objective of this study was to systematically review the literature to identify published measures that assess specialty referrals. METHODS: We performed a systematic review of the literature for measures of specialty referral. Searches were made of MEDLINE and HealthSTAR databases, references of eligible papers, and citations provided by content experts. Measures were eligible if they were published from January 1973 to June 2009, reported on validity and/or reliability of the measure, and were applicable to Organization for Economic Cooperation and Development healthcare systems. We classified measures according to a conceptual framework, which underwent content validation with an expert panel. RESULTS: We identified 2,964 potentially eligible papers. After abstract and full-text review, we selected 214 papers containing 244 measures. Most measures were applied in adults (57%), assessed structural elements of the referral process (60%), and collected data via survey (62%). Measures were classified into non-mutually exclusive domains: need for specialty care (N = 14), referral initiation (N = 73), entry into specialty care (N = 53), coordination (N = 60), referral type (N = 3), clinical tasks (N = 19), resource use (N = 13), quality (N = 57), and outcomes (N = 9). CONCLUSIONS: Published measures are available to assess the specialty referral process, although some domains are limited. Because many of these measures have been not been extensively validated in general populations, assess limited aspects of the referral process, and require new data collection, their applicability and preference in assessment of the specialty referral process is needed.
Assuntos
Medicina , Encaminhamento e Consulta/organização & administração , Humanos , Avaliação de Programas e Projetos de Saúde , Qualidade da Assistência à SaúdeRESUMO
Previous surveys found a large (>10-fold) variation in schizophrenia prevalence at different geographic sites and a tendency for prevalence to increase with latitude. We conducted meta-analyses of prevalence studies to investigate whether these findings pointed to underlying etiologic factors in schizophrenia or were the result of methodological artifacts or the confounding of sites' latitude with level of healthcare at those sites. We found that these patterns were still present after controlling for an index of healthcare--infant mortality--and focusing on 49 studies that used similar diagnostic and ascertainment methods. The tendencies for schizophrenia prevalence to increase with both latitude and colder climate were still large and significant and present on several continents. The increase in prevalence with latitude was greater for groups with low fish consumption, darker skin, and higher infant mortality--consistent with a role of prenatal vitamin D deficiency in schizophrenia. Previous research indicates that poor prenatal healthcare and nutrition increase risk for schizophrenia within the same region. These adverse conditions are more prevalent in developing countries concentrated near the equator, but schizophrenia prevalence is lowest at sites near the equator. This suggests that schizophrenia-producing environmental factors associated with higher latitude may be so powerful they overwhelm protective effects of better healthcare in industrialized countries. The observed patterns of correlations of risk factors with prevalence are consistent with an etiologic role for prenatal vitamin D deficiency and exposure to certain infectious diseases. Research to elucidate environmental factors that underlie variations in schizophrenia prevalence deserves high priority.