RESUMO
OBJECTIVES: To determine whether neonatal conjugated or direct bilirubin levels were elevated in infants with biliary atresia (BA) and to estimate the number of newborns who would have positive screens in the nursery necessitating repeat testing after discharge. STUDY DESIGN: We used administrative data from a large integrated healthcare network in Utah to identify newborns who had a fractionated bilirubin recorded during birth admission from 2005 through 2019. Elevated conjugated bilirubin was defined as greater than 0.2 mg/dL and direct bilirubin was defined as greater than 0.5 mg/dL (>97.5th percentile for the assays). We performed simulations to estimate the anticipated number of false-positive screens. RESULTS: There were 32 cases of BA and 468â161 live births during the study period (1/14 700). There were 252â892 newborns with fractionated bilirubin assessed, including 26 of those subsequently confirmed to have BA. Conjugated or direct bilirubin was elevated in all 26 infants with BA and an additional 3246 newborns (1.3%) without BA. Simulated data suggest 9-21 per 1000 screened newborns will have an elevated conjugated or direct bilirubin using laboratory-based thresholds for a positive screen. Screening characteristics improved with higher thresholds without increasing false-negative tests. CONCLUSIONS: This study validates the previous findings that conjugated or direct bilirubin are elevated in the newborn period in patients with BA. A higher threshold for conjugated bilirubin improved screening performance. Future studies are warranted to determine the optimal screening test for BA and to assess the effectiveness and cost-effectiveness of implementing such a program.
Assuntos
Atresia Biliar , Lactente , Recém-Nascido , Humanos , Atresia Biliar/diagnóstico , Bilirrubina , Estudos de Coortes , Utah/epidemiologia , Testes de Função HepáticaRESUMO
AIMS: To compare the effect on mortality and length of hospital stay of propofol with that of sodium thiopentone for the management of dogs with status epilepticus (SE) and refractory status epilepticus (RSE). METHODS: In this cohort study, medical records of a veterinary referral clinic in Argentina were retrospectively searched for dogs that were hospitalised and required induction of therapeutic coma (TC) with either propofol or sodium thiopentone for the management of SE or RSE of any cause. A logistic regression model was performed to evaluate the association between the type of anaesthetic used and in-hospital mortality adjusting for the type of epilepsy (idiopathic, structural, or reactive). Kaplan-Meier estimated survival curves for the length of hospital stay by the type of anaesthetic drug were compared using the log-rank test (deaths were considered censored events). Cox proportional hazards regression was used to estimate hazard ratios for time to hospital discharge, unadjusted and adjusted for type of epilepsy. RESULTS: A total of 24 dogs with SE were included in the study: eight treated with propofol and 16 treated with sodium thiopentone. Four dogs treated with propofol (proportion = 0.50; 95% CI = 0.15-0.84), and eight treated with sodium thiopentone (proportion = 0.50; 95% CI = 0.50-0.74) died during hospitalisation. The median hospitalisation time was 43 (IQR 24-56) hours for dogs that were treated with propofol and 72 (IQR 64-96) hours for dogs that were treated with sodium thiopentone. There was no evidence of a difference in the median duration of TC in dogs treated with propofol (12 (IQR 8-24) hours) or with sodium thiopentone (12 (IQR 7.5-20) hours; p = 0.946). In the logistic regression model, no evidence of association between the anaesthetic protocol for the management of RSE and in-hospital mortality, adjusted for the type of epilepsy, was found (OR 1.09 (95% CI = 0.17-6.87); p = 0.925). Cox regression analysis revealed a difference in the time to hospital discharge, adjusted by the type of epilepsy, between treatment groups (HR = 0.05 (95% CI = 0.01-0.54); p = 0.013). CONCLUSIONS AND CLINICAL RELEVANCE: The time spent in hospital before discharge was longer in dogs with RSE treated with sodium thiopentone compared to those treated with propofol. However, as the sample size was very small, the results obtained in the present study should be analysed with caution. Further studies including a greater number of dogs are required.
Assuntos
Anestésicos , Doenças do Cão , Propofol , Estado Epiléptico , Cães , Animais , Tiopental/uso terapêutico , Tiopental/farmacologia , Propofol/uso terapêutico , Propofol/farmacologia , Estudos de Coortes , Estudos Retrospectivos , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/veterinária , Anestésicos/uso terapêutico , Sódio/uso terapêutico , Doenças do Cão/tratamento farmacológicoRESUMO
OBJECTIVE: To investigate patient factors predictive of gamma glutamyltransferase (GGT) normalization following ursodeoxycholic acid (UDCA) therapy in children with primary sclerosing cholangitis. STUDY DESIGN: We retrospectively reviewed patient records at 46 centers. We included patients with a baseline serum GGT level ≥50 IU/L at diagnosis of primary sclerosing cholangitis who initiated UDCA therapy within 1 month and continued therapy for at least 1 year. We defined "normalization" as a GGT level <50 IU/L without experiencing portal hypertensive or dominant stricture events, liver transplantation, or death during the first year. RESULTS: We identified 263 patients, median age 12.1 years at diagnosis, treated with UDCA at a median dose of 15 mg/kg/d. Normalization occurred in 46%. Patients with normalization had a lower prevalence of Crohn's disease, lower total bilirubin level, lower aspartate aminotransferase to platelet ratio index, greater platelet count, and greater serum albumin level at diagnosis. The 5-year survival with native liver was 99% in those patients who achieved normalization vs 77% in those who did not. CONCLUSIONS: Less than one-half of the patients treated with UDCA have a complete GGT normalization in the first year after diagnosis, but this subset of patients has a favorable 5-year outcome. Normalization is less likely in patients with a Crohn's disease phenotype or a laboratory profile suggestive of more advanced hepatobiliary fibrosis. Patients who do not achieve normalization could reasonably stop UDCA, as they are likely not receiving clinical benefit. Alternative treatments with improved efficacy are needed, particularly for patients with already-advanced disease.
Assuntos
Colangite Esclerosante/sangue , Colangite Esclerosante/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico , gama-Glutamiltransferase/sangue , Adolescente , Análise de Variância , Biomarcadores/sangue , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Testes de Função Hepática , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Falha de Tratamento , Resultado do TratamentoRESUMO
BACKGROUND: Endothelial thrombomodulin (TM) is critically involved in anticoagulation, anti-inflammation, cytoprotection and normal fetal development. Tumor necrosis factor alpha (TNFα) suppresses TM expression. OBJECTIVE: TNFα has been shown to down-regulate TM partly via activation of nuclear factor kappa B (NF-κB). However, because the TM promoter lacks an NF-κB binding site, the direct involvement of NF-κB has been controversial. We investigated the role of the upstream regulatory serine kinase, inhibitory kappa-B kinase-ß (IKKß), in TM expression and function with or without TNFα treatment. METHODS: Inhibition of IKKß was achieved by specific chemical inhibitors, siRNA or shRNA. TM expression was assessed by qRT-PCR, Western blot, flow cytometry, luciferase reporter assay and chromatin immune-precipitation (ChIP) assay. TM function was estimated by generation of activated protein C (APC). NF-κB activation was determined by immunocytochemistry. RESULTS AND CONCLUSIONS: IKKß inhibition increased TM expression and function, and attenuated TNFα-mediated TM down-regulation. In contrast, inhibition of downstream canonical NF-κB protein family members p50 and p65 (RelA) failed to up-regulate TM expression and did not affect IKKß inhibition-mediated TM over-expression. However, knockdown of cRel and RelB, family members of the canonical and non-canonical NF-κB pathway, respectively, resulted in TM over-expression. IKKß inhibition caused over-expression, increased promoter activity and enhanced binding of Krüppel-like factor 2 (Klf2) to the TM promoter, which positively regulates TM expression. Finally, knockdown of Klf2 completely attenuated IKKß inhibition-mediated TM up-regulation. We conclude that IKKß regulates TM in a Klf2-dependent manner.
Assuntos
Endotélio Vascular/metabolismo , Regulação da Expressão Gênica , Quinase I-kappa B/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , NF-kappa B/metabolismo , Trombomodulina/metabolismo , Anti-Inflamatórios/química , Anticoagulantes/química , Sítios de Ligação , Imunoprecipitação da Cromatina , Regulação para Baixo , Citometria de Fluxo , Células HEK293 , Células Endoteliais da Veia Umbilical Humana , Humanos , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Proteína C/metabolismo , RNA Interferente Pequeno/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To assess sustained immunosuppression-free remission (SIFR) in children with autoimmune hepatitis (AIH). STUDY DESIGN: We retrospectively reviewed all children with AIH in the region between 1986 and 2011 using a population-based methodology. RESULTS: We identified 56 children with AIH (62.5% females; median age, 11.1 years [IQR, 5.7-14.4 years], followed for a median of 5.6 years [IQR, 2.8-8.6 years]). Liver disease was characterized by type II AIH in 8.9%, cirrhosis in 14.0%, and primary sclerosing cholangitis in 21.4%. Coexisting nonhepatic immune-mediated diseases occurred in 37.5%. Biochemical remission on immunosuppressive therapy was achieved in 76.4% of all patients with AIH at a median of 1.2 years (IQR, 0.4-3.6 years); 23.1% of these patients experienced a subsequent relapse. Discontinuation of all immunosuppressive medications was attempted in 16 patients and was successful in 14 patients (87.5%) with type 1 AIH (median age at discontinuation, 8.9 years [IQR, 3.5-17.9 years], treated for a median of 2.0 years [IQR, 1.3-3.5 years] after diagnosis), with SIFR occurring at a median of 3.4 years (IQR, 2.6-5.8 years) of follow-up. Excluding patients with inflammatory bowel disease who received immunosuppressive therapy independent of their liver disease, the probability of achieving SIFR within 5 years of diagnosis of AIH was 41.6% (95% CI, 25.3%-62.9%). Baseline patient characteristics associated with an inability to achieve biochemical remission on immunosuppression or SIFR were elevated international normalized ratio, positive antineutrophil cytoplasmic antibody titer, cirrhosis, and a nonhepatic autoimmune disorder. CONCLUSION: We found a high rate of successful discontinuation of all immunosuppressive medications in carefully selected patients with AIH in a population-based cohort. SIFR is an achievable goal for children with AIH, particularly those with type I disease in stable biochemical remission on immunosuppressive therapy.
Assuntos
Hepatite Autoimune/tratamento farmacológico , Imunossupressores/administração & dosagem , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Terapia de Imunossupressão , Lactente , Masculino , Indução de Remissão , Estudos RetrospectivosRESUMO
Genetic variation in fatty acid desaturases (FADS) has previously been linked to long-chain polyunsaturated fatty acids (PUFAs) in adipose tissue and cardiovascular risk. The goal of our study was to test associations between six common FADS polymorphisms (rs174556, rs3834458, rs174570, rs2524299, rs174589, rs174627), intermediate cardiovascular risk factors, and non-fatal myocardial infarction (MI) in a matched population based case-control study of Costa Rican adults (n = 1756). Generalized linear models and multiple conditional logistic regression models were used to assess the associations of interest. Analyses involving intermediate cardiovascular risk factors and MI were also conducted in two replication cohorts, The Nurses' Health Study (n = 1200) and The Health Professionals Follow-Up Study (n = 1295). In the Costa Rica Study, genetic variation in the FADS cluster was associated with a robust linear decrease in adipose gamma-linolenic, arachidonic, and eicosapentaenoic fatty acids, and significant or borderline significant increases in the eicosadienoic, eicosatrienoic, and dihomo-gamma-linolenic fatty acids. However, the associations with adipose tissue fatty acids did not translate into changes in inflammatory biomarkers, blood lipids, or the risk of MI in the discovery or the replication cohorts. In conclusion, fatty acid desaturase polymorphisms impact long-chain PUFA biosynthesis, but their overall effect on cardiovascular health likely involves multiple pathways and merits further investigation.
RESUMO
BACKGROUND/OBJECTIVES: Elongases 2, 4 and 5, encoded by genes ELOVL2, ELOVL4 and ELOVL5, have a key role in the biosynthesis of very long chain polyunsaturated fatty acids (PUFAs). To date, few studies have investigated the associations between elongase polymorphisms and cardiovascular health. We investigated whether ELOVL polymorphisms are associated with adipose tissue fatty acids, serum lipids, inflammation and ultimately with nonfatal myocardial infarction (MI) in a Costa Rican population. SUBJECTS/METHODS: MI cases (n=1650) were matched to population-based controls (n=1650) on age, sex and area of residence. Generalized linear and multiple conditional logistic regression models were used to assess the associations between seven common ELOVL polymorphisms and cardiometabolic outcomes. Analyses were replicated in The Nurses' Health Study (n=1200) and The Health Professionals Follow-Up Study (n=1295). RESULTS: Variation in ELOVL2, ELOVL4 and ELOVL5 was not associated with adipose tissue fatty acids, intermediate cardiovascular risk factors or MI. In the Costa Rica study, the number of the minor allele copies at rs2294867, located in the ELOVL5 gene, was associated with an increase in total and LDL cholesterol (adjusted P-values=0.001 and <0.0001 respectively). Additionally, the number of the minor allele copies at rs761179, also located in the ELOVL5 gene, was significantly associated with an increase in total cholesterol (adjusted P-value=0.04). However, the observed associations were not replicated in independent populations. CONCLUSION: Common genetic variants in elongases are not associated with adipose tissue fatty acids, serum lipids, biomarkers of systemic inflammation, or the risk of MI.
Assuntos
Acetiltransferases/genética , Doenças Cardiovasculares/genética , Colesterol/genética , Ácidos Graxos Insaturados/genética , Inflamação/genética , Infarto do Miocárdio/genética , Polimorfismo Genético , Tecido Adiposo/metabolismo , Idoso , Alelos , Estudos de Casos e Controles , Colesterol/sangue , LDL-Colesterol/sangue , LDL-Colesterol/genética , Costa Rica , Elongases de Ácidos Graxos , Ácidos Graxos Insaturados/biossíntese , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de RiscoRESUMO
BACKGROUND AND AIMS: To examine whether the association between the -514 C/T polymorphism of the hepatic lipase gene and myocardial infarction (MI) is modified by history of hypercholesterolemia and increased waist circumference. METHODS AND RESULTS: A total of 1940 pairs of nonfatal MI cases and population-based controls were genotyped. Multiple conditional logistic regression was used for data analyses. The -514T variant was not associated with MI in the whole population. However, among people with history of hypercholesterolemia the T allele increased MI risk for heterozygous and homozygous carriers, respectively [OR=1.25 (95%CI=0.92-1.70) and OR=1.59 (95%CI=1.09-2.32). In contrast, the T allele decreased MI risk among people with no history of hypercholesterolemia [OR=0.85 (95%CI=0.70-1.03) and OR=0.76 (95%CI=0.60-0.97)], p for interaction=0.004. Among subjects with normal waist circumference there was no association between the -514T allele and MI for heterozygous and homozygous carriers, respectively [OR=1.04 (95%CI=0.86-1.25) and OR=0.96 (95%CI=0.77-1.21)], while among subjects with waist circumference above the limits of the metabolic syndrome definition there was a protective association [OR=0.63 (95%CI=0.45-0.90) and OR=0.81 (95%CI=0.53-1.25) p for interaction=0.04]. CONCLUSION: The -514T allele is associated with MI in opposite directions depending on the background of the studied population. This could explain what seem like inconsistent results across studies.
Assuntos
Hipercolesterolemia/complicações , Lipase/genética , Infarto do Miocárdio/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Circunferência da Cintura , Idoso , Estudos de Casos e Controles , Costa Rica , Feminino , Frequência do Gene , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Funções Verossimilhança , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/enzimologia , Razão de Chances , Medição de Risco , Fatores de RiscoRESUMO
Microfungi were collected in southern Mexico in the vicinity of Puerto Escondido, Oaxaca in 2007. In 2006, samples were gathered from Acacia myrmecophytes [(Remarkable microfungi from Oaxaca of Acacia species) Part I]. In the present investigation [Part II], we collected microfungi from different parts of a variety of wild and cultivated higher plants belonging to the families Anacardiaceae, Caricaceae, Fabaceae, Moraceae, and Nyctaginacae. The microfungi found here live as parasites or saprophytes. Interestingly, the species Colletotrichum lindemuthianum (Sacc. and Magn.) Briosi and Cavara has repeatedly been used to cause fungal infections of Phaseolus lunatus leaves in laboratory experiments. We could now find the same fungus as parasite on the same host plants under field conditions showing that results obtained in the laboratory are also relevant in nature. Most of the fungal species collected belong to the classes Ascomycotina, Basidiomycotina and Deuteromycotina. Until now, some of the microfungi identified in this study have been rarely observed before or have been reported for the first time in Mexico, for example: Pestalotia acaciae Thüm. on Acacia collinsii Safford; Corynespora cassiicola (Berk. and M.A. Curtis) C.T. Wei on Carica papaya L.; Botryosphaeria ribis Grossenb. and Duggar and Cercosporella leucaenae (Raghu Ram and Mallaiah) U. Braun (new for Mexico) and Camptomeris leucaenae (F. Stevens and Dalbey) Syd. (new for Mexico) on Leucaena leucocephala (Lam.) de Wit.; Oidium clitoriae Narayanas. and K. Ramakr. and Phakopsora cf. pachyrhizi Sydow and Sydow (new for Mexico) on Clitoria ternatea L.; Botryosphaeria obtusa (Schw.) Shoemaker on Prosopis juliflora (Sw.) DC.; Cylindrocladium scoparium Morg. on Ficus benjamina L.; Acremonium sp. on Bougainvillea sp. All specimens are located in the herbarium ESS. Mycotheca Parva collection G.B. Feige and N. Ale-Agha.
Assuntos
Fungos/classificação , Fungos/isolamento & purificação , Filogenia , Doenças das Plantas/microbiologia , Fungos/patogenicidade , México , Plantas/microbiologiaRESUMO
In the state of Oaxaca (Mexico, 10 km north-west of Puerto Escondido 15 degrees 55' N, 97 degrees 09' W) we were able to collect some microfungi living as parasites or saprophytes on Acacia species, some of them are causing attention for Oaxaca. Many belong to the Deuteromycotina (Hyphomycetes, Coelomycetes) and Ascomycotina. On A. hindsii: Calonectria pseudopeziza (Desm.) Sacc., Hypoxylon truncatum (Schwein. Fr.) J.H. Miller, Epicoccum nigrum Link., Zygosporium gibbum (Sacc., M. Roussau & E. Bommer) S.J. Hughes and on A. cornigera: Phyllosticta acaciicola P. Henn., Taeniolella alta (Ehrenb. ex Pers.) S.J. Hughes, Cephaliophora tropica Thaxt., Diplodia mutila (Fr. Fr.) Mont., Pleospora herbarum (Pers. Fr.) Rabenh., Gliocladium roseum Bainier, Ulocladium atrum Preuss., and different others. All species collected are listed in text.