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1.
Sci Rep ; 11(1): 4986, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654186

RESUMO

Diagnosis of biliary atresia (BA) can involve uncertainties. In the present prospective multicenter study, we considered whether urinary oxysterols represent a useful marker for diagnosis of BA in Japanese children. Subjects under 6 months old at 7 pediatric centers in Japan were prospectively enrolled, including patients with cholestasis and healthy controls (HC) without liver disease. Patients with cholestasis constituted 2 groups representing BA patients and others with cholestasis from other causes (non-BA). We quantitatively analyzed 7 oxysterols including 4ß-, 20(S)-, 22(S)-, 22(R)-, 24(S)-, 25-, and 27-hydroxycholesterol by liquid chromatography/electrospray ionization-tandem mass spectrometry. Enrolled subjects included 14 with BA (median age 68 days; range 26-170) and 10 non-BA cholestatic controls (59; 14-162), as well as 10 HC (57; 25-120). Total urinary oxysterols were significantly greater in BA (median, 153.0 µmol/mol creatinine; range 24.1-486.7; P < 0.001) and non-BA (36.2; 5.8-411.3; P < 0.05) than in HC (2.7; 0.8-7.6). In patients with BA, urinary 27-hydroxycholesterol (3.61; 0.42-11.09; P < 0.01) was significantly greater than in non-BA (0.71; 0-5.62). In receiver operating characteristic (ROC) curve analysis for distinguishing BA from non-BA, the area under the ROC curve for urinary 27-hydroxycholesterol was 0.83. In conclusion, this first report of urinary oxysterol analysis in patients with BA indicated that 27-hydroxycholesterol may be a useful marker for distinguishing BA from other causes of neonatal cholestasis.


Assuntos
Atresia Biliar/urina , Hidroxicolesteróis/urina , Biomarcadores/urina , Feminino , Humanos , Lactente , Recém-Nascido , Japão , Masculino , Espectrometria de Massas , Estudos Prospectivos
2.
Sci Rep ; 10(1): 6752, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32317688

RESUMO

Few reports describe oxysterols in healthy children or in children with liver disease. We aimed to determine whether developmental changes in urinary and serum oxysterols occur during childhood, and to assess whether oxysterols might be biomarkers for pediatric liver disease. Healthy children enrolled as subjects (36 and 35 for urine and serum analysis, respectively) included neonates, infants, preschoolers, and school-age children, studied along with 14 healthy adults and 8 children with liver disease. We quantitated 7 oxysterols including 4ß-, 20(S)-, 22(S)-, 22(R)-, 24(S)-, 25-, and 27-hydroxycholesterol using liquid chromatography/electrospray ionization-tandem mass spectrometry. Urinary total oxysterols were significantly greater in neonates than in infants (P < 0.05), preschoolers (P < 0.001), school-age children (P < 0.001), or adults (P < 0.001), declining with age. Serum total oxysterols in neonates were significantly lower than in infants (P < 0.05), preschoolers (P < 0.001), school-age children (P < 0.05), or adults (P < 0.01). Compared with healthy children, total oxysterols and 24(S)-hydroxycholesterol in liver disease were significantly increased in both urine (P < 0.001 and P < 0.001, respectively) and serum (P < 0.001 and P < 0.05, respectively). Oxysterols in liver disease, particularly 24(S)-hydroxycholesterol, were greater in urine than serum. Oxysterols change developmentally and might serve as a biomarker for pediatric liver disease. To our knowledge, this is the first such report.


Assuntos
Atresia Biliar/diagnóstico , Cisto do Colédoco/diagnóstico , Colestase Intra-Hepática/diagnóstico , Hepatite Autoimune/diagnóstico , Falência Hepática Aguda/diagnóstico , Oxisteróis , Adolescente , Adulto , Fatores Etários , Atresia Biliar/sangue , Atresia Biliar/patologia , Atresia Biliar/urina , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Criança , Pré-Escolar , Cisto do Colédoco/sangue , Cisto do Colédoco/patologia , Cisto do Colédoco/urina , Colestase Intra-Hepática/sangue , Colestase Intra-Hepática/patologia , Colestase Intra-Hepática/urina , Feminino , Hepatite Autoimune/sangue , Hepatite Autoimune/patologia , Hepatite Autoimune/urina , Humanos , Lactente , Recém-Nascido , Fígado/metabolismo , Fígado/patologia , Falência Hepática Aguda/sangue , Falência Hepática Aguda/patologia , Falência Hepática Aguda/urina , Masculino , Pessoa de Meia-Idade , Oxisteróis/sangue , Oxisteróis/urina , Espectrometria de Massas por Ionização por Electrospray
3.
J Surg Res ; 228: 228-237, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29907216

RESUMO

BACKGROUND: Biliary atresia (BA) is difficult to distinguish from other causes of cholestasis. We evaluated the use of liquid chromatography-mass spectroscopy (LC-MS) and bile acid profiles in the rapid, noninvasive diagnosis of BA. MATERIALS AND METHODS: Following Institutional Animal Care and Use Committee and Institutional Review Board approval, we used LC-MS to measure 26 bile acids in serum and stool samples from experimental models of BA and in urine, stool, and serum samples from non-cholestatic and cholestatic human infants. RESULTS: We first evaluated the utility of LC-MS to distinguish bile acid profiles between sham, bile duct ligation, and 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse models of BA. Serum bile acids were significantly higher and stool bile acids were significantly lower in experimental BA. Next, we evaluated samples from non-cholestatic, cholestatic non-BA, and BA infants. There was no significant difference between cholestatic non-BA and BA stool and urine samples. However, primary bile acids were significantly higher in BA versus cholestatic non-BA samples (128.1 ± 14.2 versus 61.2 ± 20.5 µM). In addition, the primary, conjugated bile acids glycochenodeoxycholic acid and taurochenodeoxycholic acid were significantly elevated in BA compared with cholestatic non-BA serum samples. Using a receiver operating characteristic curve, we found that a serum glycochenodeoxycholic acid concentration of 30 µM had a sensitivity of 100%, specificity of 83.3%, positive predictive value of 88.9%, and negative predictive value of 100% in the diagnosis of BA. CONCLUSIONS: Our data indicate that bile acid patterns can be used to distinguish experimental and human BA from non-cholestatic and, more importantly, cholestatic disease. This suggests that LC-MS may be useful in the accurate, rapid, and non-invasive diagnosis of BA.


Assuntos
Ácidos e Sais Biliares/análise , Atresia Biliar/diagnóstico , Colestase/diagnóstico , Hiperbilirrubinemia/sangue , Espectrometria de Massas/métodos , Adolescente , Animais , Atresia Biliar/sangue , Atresia Biliar/complicações , Atresia Biliar/urina , Criança , Pré-Escolar , Colestase/sangue , Colestase/etiologia , Colestase/urina , Cromatografia Líquida de Alta Pressão/métodos , Diagnóstico Diferencial , Modelos Animais de Doenças , Fezes/química , Feminino , Humanos , Hiperbilirrubinemia/etiologia , Hiperbilirrubinemia/urina , Lactente , Recém-Nascido , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos
4.
Metabolomics ; 14(7): 90, 2018 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-30830373

RESUMO

INTRODUCTION: Neonatal cholestatic disorders are a group of hepatobiliary diseases occurring in the first 3 months of life. The most common causes of neonatal cholestasis are infantile hepatitis syndrome (IHS) and biliary atresia (BA). The clinical manifestations of the two diseases are too similar to distinguish them. However, early detection is very important in improving the clinical outcome of BA. Currently, a liver biopsy is the only proven and effective method used to differentially diagnose these two similar diseases in the clinic. However, this method is invasive. Therefore, sensitive and non-invasive biomarkers are needed to effectively differentiate between BA and IHS. We hypothesized that urinary metabolomics can produce unique metabolite profiles for BA and IHS. OBJECTIVES: The aim of this study was to characterize urinary metabolomic profiles in infants with BA and IHS, and to identify differences among infants with BA, IHS, and normal controls (NC). METHODS: Urine samples along with patient characteristics were obtained from 25 BA, 38 IHS, and 38 NC infants. A non-targeted gas chromatography-mass spectrometry (GC-MS) metabolomics method was used in conjunction with orthogonal partial least squares discriminant analysis (OPLS-DA) to explore the metabolomic profiles of BA, IHS, and NC infants. RESULTS: In total, 41 differentially expressed metabolites between BA vs. NC, IHS vs. NC, and BA vs. IHS were identified. N-acetyl-D-mannosamine and alpha-aminoadipic acid were found to be highly accurate at distinguishing between BA and IHS. CONCLUSIONS: BA and IHS infants have specific urinary metabolomic profiles. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be used to discriminate BA from IHS.


Assuntos
Atresia Biliar/metabolismo , Hepatite/metabolismo , Metabolômica , Atresia Biliar/urina , Feminino , Hepatite/urina , Humanos , Lactente , Masculino
5.
Pediatr Int ; 53(4): 497-500, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21040191

RESUMO

BACKGROUND: Measurement of urinary sulfated bile acid (USBA) is a non-invasive method to detect bile congestion. Our aim was to evaluate the feasibility of USBA analysis for the early detection of biliary atresia (BA). METHODS: We determined the USBA-to-creatinine ratio (USBA/cr) in 1148 infants at 10-40 days after birth. All infants were followed until the 3- to 4-month postnatal routine health check. The cutoff value for USBA/cr was 55.0 µmol/g creatinine. RESULTS: Among the infants tested, 47 (4.10%) had USBA/cr ratios that exceeded the cutoff value. Two of these 47 infants had liver disease; one was diagnosed with neonatal hepatitis syndrome, and the other was diagnosed with BA. The BA patient underwent USBA analysis for the first time on day 18 after birth and hepatoportoenterostomy on day 49. No other infants were diagnosed with hepatobiliary disease during the follow-up period. CONCLUSION: This USBA analysis provided the correct assessment without fail and identified a case of BA. This approach could be used for the screening and early detection of BA when the false-positive rate is decreased by improving the methods for sample collection and urine storage.


Assuntos
Ácidos e Sais Biliares/urina , Atresia Biliar/diagnóstico , Atresia Biliar/urina , Biomarcadores/urina , Creatinina/urina , Diagnóstico Precoce , Estudos de Viabilidade , Seguimentos , Humanos , Lactente , Recém-Nascido , Triagem Neonatal , Projetos Piloto
7.
Med Sci Monit ; 9(3): MT21-31, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12640349

RESUMO

BACKGROUND: It is well known that urine becomes the major route for bile acid excretion in liver diseases and thus we examined bile acid profile in urine obtained from normal children and children having chronic liver diseases using electrospray tandem mass spectrometry (ES/MS/MS). MATERIAL/METHODS: Bile acid were extracted from 5 ml of urine obtained from five healthy children or from twenty patients with various liver diseases including patients with unknown chronic liver diseases, Zellweger syndrome, peroxisomal bifunctional protein deficiency disease, tyrosinema type 1, biliary atresia, and patients with progressive familial intrahepatic cholestasis (PFIC) of undetermined type. Identification and quantification of bile acids were achieved in 5 minutes using electrospray tandem mass spectrometry (ES/MS/MS). RESULTS: Urinary bile acid excretion increased in liver diseases an average of 100 times as compared to control values. There was a specific profile for different liver disease which confirms the pathology of the disease and could be used for its diagnosis. The results also show that the ions used for the diagnosis of oxo-steroid reductase deficiency disease were present in other chronic liver diseases suggesting that these atypical bile acids may not be a result of an inborn error of bile acid metabolism. CONCLUSIONS: The urinary bile acid profile obtained in this study by ES/MS/MS can be of use for the diagnosis of certain chronic liver diseases.


Assuntos
Ácidos e Sais Biliares/urina , Colestase/urina , Erros Inatos do Metabolismo/urina , Espectrometria de Massas por Ionização por Electrospray/métodos , Atresia Biliar/urina , Estudos de Casos e Controles , Criança , Pré-Escolar , Colestase Intra-Hepática/genética , Colestase Intra-Hepática/urina , Doença Crônica , Humanos , Hepatopatias/diagnóstico , Hepatopatias/urina , Transtornos Peroxissômicos/urina , Valores de Referência , Síndrome , Tirosinemias/urina
8.
Clin Exp Pharmacol Physiol Suppl ; (29): S19-22, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12355909

RESUMO

1. Biliary atresia (BA), as a common disease in Japan, and cystic fibrosis (CF), as an extremely uncommon disease in Japan, were selected to assess the clinical significance of measurement of energy expenditure (EE). 2. Energy expenditure was significantly higher in children with BA than in normal children. 3. Measurement of EE in BA lead to clues to resolving its mechanism by novel assessment of interleukin-6 and leptin. 4. Energy expenditure in children with CF is also higher, but this has been addressed by nutritional intervention with additional calories. 5. Individualization of EE measurement is necessary in the analysis of pathological mechanisms and nutritional management of patients with both common and uncommon diseases.


Assuntos
Metabolismo Energético/fisiologia , Adolescente , Atresia Biliar/sangue , Atresia Biliar/fisiopatologia , Atresia Biliar/urina , Calorimetria Indireta/métodos , Criança , Pré-Escolar , Fibrose Cística/sangue , Fibrose Cística/fisiopatologia , Fibrose Cística/urina , Humanos , Lactente , Japão
9.
J Hepatol ; 28(2): 270-9, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9514540

RESUMO

BACKGROUND/AIMS: Urinary 3-oxo-delta4 bile acids have been detected in infants who ultimately died of liver disease. We used qualitative and quantitative methods to compare urinary 3-oxo-delta4 bile acids in liver disease, determining their composition and evaluating the prognostic implication in patients of various ages with various liver diseases. METHODS: Gas chromatography-mass spectrometry was used to measure 3-oxo-delta4 bile acids in the urine of patients and healthy controls. RESULTS: Patients with a deficiency of 3-oxo-delta4-steroid 5beta-reductase and acute hepatic failure exhibited a significantly higher percentage of 3-oxo-delta4 bile acids in total bile acids in urine than the healthy controls or other patient groups, including those with neonatal cholestasis or biliary atresia (p<0.0001). The urinary 3-oxo-delta4 bile acids in patients with 3-oxo-delta4-steroid 5beta-reductase deficiency who had a poor prognosis were mainly 7alpha-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochola-4,6-dien-24-oic acid. CONCLUSIONS: Our results indicate that an increase in the 7alpha-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochola-4,6-dien-24-oic acid in the urine of patients with hepatobiliary disease indicates a poor prognosis.


Assuntos
Atresia Biliar/urina , Ácido Quenodesoxicólico/análogos & derivados , Colestase/urina , Hepatopatias/urina , Oxirredutases/deficiência , Adolescente , Adulto , Idoso , Atresia Biliar/complicações , Estudos de Casos e Controles , Ácido Quenodesoxicólico/urina , Criança , Pré-Escolar , Colestase/etiologia , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Lactente , Hepatopatias/complicações , Masculino , Pessoa de Meia-Idade
10.
J Pediatr ; 129(2): 306-8, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8765633

RESUMO

Direct enzymatic assay of urinary sulfated bile acids is a sensitive, rapid, minimally invasive, and convenient method of detecting cholestasis in young infants. It may replace measurement of serum direct bilirubin for selective screening for biliary atresia and neonatal hepatitis syndrome at 1 month of age.


Assuntos
Ácidos e Sais Biliares/urina , Bilirrubina/sangue , Colestase/diagnóstico , Triagem Neonatal , Atresia Biliar/sangue , Atresia Biliar/diagnóstico , Atresia Biliar/urina , Colestase/sangue , Colestase/urina , Feminino , Hepatite/sangue , Hepatite/diagnóstico , Hepatite/urina , Humanos , Lactente , Recém-Nascido , Masculino , Sensibilidade e Especificidade , Sulfatos/urina , Síndrome
12.
J Pediatr ; 120(3): 404-8, 1992 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1538286

RESUMO

To investigate the association of glomerular involvement with biliary atresia, we carried out the following studies: (1) review of the clinical records of 120 patients, (2) histologic study of the kidneys obtained at autopsy from 28 patients, and (3) measurements of circulating immune complexes. Of 90 patients with adequate follow-up information, 40 (44.4%) had hematuria, proteinuria, or both. All the kidney specimens showed a wide variety of mesangial proliferation, and immunoglobulins were present in 23 of 26 cases. There was a good correlation between the glomerular alterations and the period of reduced hepatic function. When IgA was present in the mesangium, IgA2 and secretory components were detected. Elevated serum IgA and circulating IgA-containing immune complex levels were found in patients with prolonged obstructive jaundice. These findings indicate that glomerular alterations may occur subsequently in patients with biliary atresia, and that IgA of intestinal mucosal origin plays some role in the development of these lesions.


Assuntos
Atresia Biliar/patologia , Glomérulos Renais/patologia , Complexo Antígeno-Anticorpo/análise , Atresia Biliar/imunologia , Atresia Biliar/urina , Criança , Pré-Escolar , Hematúria , Humanos , Imunoglobulinas/análise , Lactente , Glomérulos Renais/imunologia , Proteinúria
13.
Lancet ; 1(8635): 421-3, 1989 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-2563796

RESUMO

To assess whether clinicopathological features other than the age at operation influence prognosis after surgery for extrahepatic biliary atresia (EHBA) and to determine whether the age at referral has fallen since a previous survey, 50 consecutive cases with EHBA referred between February, 1985, and December, 1987, were reviewed. Liver or spleen size, liver function tests, or histological appearance of liver biopsy specimen before surgery were not predictive of outcome. The jaundice cleared up in 12 of 14 children operated on by age 8 weeks, but in only 13 of 36 operated on later. In 41 referral was delayed. All 25 children in whom surgery was successful are alive and well, while 13 of 25 with unsuccessful surgery have died, at a median age of 1 year. To improve the prognosis of infants with EHBA parents and health staff need a better awareness of the early clinical features of EHBA and of the necessity for prompt referral. Liver disease should be suspected in any infant jaundiced after 14 days of age.


Assuntos
Atresia Biliar/cirurgia , Encaminhamento e Consulta , Fatores Etários , Atresia Biliar/complicações , Atresia Biliar/mortalidade , Atresia Biliar/urina , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Icterícia Neonatal/etiologia , Icterícia Neonatal/urina , Masculino , Portoenterostomia Hepática , Prognóstico , Estudos Retrospectivos
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