RESUMO
Patients with primary biliary cirrhosis have an abnormally high incidence of urinary tract infection (35%). Susceptibility to urinary infection and other infectious diseases has been linked with certain blood group antigens and secretor status. We have therefore studied these characteristics in patients with primary biliary cirrhosis. We were unable to show any abnormal distribution in blood groups or secretor status in patients with primary biliary cirrhosis (compared with a normal population) which might reflect their predisposition to urinary infection. The distribution of blood groups and secretor status in patients with primary biliary cirrhosis with a history of urinary infections was not significantly different from patients without such a history. Escherichia coli strains isolated from patients with primary biliary cirrhosis did not bind in any greater numbers to the uroepithelial cells of primary biliary cirrhosis patients than to the cells of a normal healthy control. We therefore conclude that blood group distribution, abnormal secretor status, and epithelial cell type are not important factors in the predisposition of primary biliary cirrhosis patients to urinary infections.
Assuntos
Bacteriúria/etiologia , Cirrose Hepática Biliar/complicações , Sistema ABO de Grupos Sanguíneos/imunologia , Adesividade , Adulto , Idoso , Bacteriúria/sangue , Bacteriúria/imunologia , Escherichia coli/fisiologia , Feminino , Humanos , Isoantígenos/análise , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/imunologia , Masculino , Pessoa de Meia-Idade , Sistema do Grupo Sanguíneo P , Recidiva , Saliva/imunologiaRESUMO
The distributions of ABO, rhesus, and Lewis blood group antigens were studied in patients with alcoholic cirrhosis, alcoholic pancreatitis, chronic active hepatitis, and primary biliary cirrhosis. There were no differences in frequencies of ABO and rhesus blood group antigens between the groups or in comparison with a control group of blood donors. Lewis phenotype Le (a- b-), however, was more common on erythrocytes than in saliva in patients with alcoholic cirrhosis, alcoholic pancreatitis, and severe renal disease but equally common in saliva and on red blood cells in patients with non-alcoholic liver disease. It is suggested that Lewis typing should be performed on saliva because blood typing may give misleading results in some patients.
Assuntos
Alcoolismo/sangue , Eritrócitos/análise , Antígenos do Grupo Sanguíneo de Lewis , Cirrose Hepática Alcoólica/sangue , Pancreatite/sangue , Saliva/análise , Sistema ABO de Grupos Sanguíneos , Doença Aguda , Adulto , Feminino , Hepatite/sangue , Humanos , Falência Renal Crônica/sangue , Cirrose Hepática Biliar/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Sistema do Grupo Sanguíneo Rh-HrRESUMO
Serum squalene levels did not change in patients with acute hepatitis, chronic active hepatitis and liver cirrhosis, but were significantly reduced in patients with intra- and extrahepatic cholestasis. The ratio of cholesterol to squalene remained normal in patients with acute hepatitis as well as chronic active hepatitis, while being slightly decreased in patients with liver cirrhosis. On the other hand, in patients with cholestasis the ratio was markedly raised. From these observations we confirmed abnormal sterol metabolism in hepatobiliary diseases, and clinical usefulness of the ratio of cholesterol to squalene to distinguish hepatocellular injury and cholestasis.
Assuntos
Doenças Biliares/sangue , Hepatopatias/sangue , Esqualeno/sangue , Doença Aguda , Adulto , Azatioprina/farmacologia , Colestase/sangue , Colesterol/sangue , Resina de Colestiramina/farmacologia , Doença Crônica , Feminino , Hepatite/sangue , Humanos , Cirrose Hepática/sangue , Cirrose Hepática Biliar/sangue , Masculino , Fenobarbital/farmacologiaRESUMO
A rapid and simple method for the quantitative determination of human serum apo E-rich high-density lipoproteins is described. A sample was divided into two parts; one part was mixed with an equal volume of 13% polyethylene glycol 6000, and the other part was mixed with a solution containing dextran sulfate, sodium phosphotungstate, and Mg2+, respectively. The mixed solutions were centrifuged (2000 g; 15 min). The supernate obtained by the former procedure contained both apo E-rich HDL and apo E-poor HDL, but that obtained by the latter procedure contained solely apo E-poor HDL. The serum apo E-rich HDL concentration in terms of apo E (E) and cholesterol (C), was given by the following equations: E = EP x 2, and C = (CP - CD) x 2, where EP and CP were the concentrations of apo E and cholesterol, respectively, in the supernate obtained with 13% polyethylene glycol, and CD was the concentration of cholesterol in the supernate obtained with the mixture solution of dextran sulfate, sodium phosphotungstate, and Mg2+. Normal serum apo E-rich HDL concentrations were 2.6 +/- 1.5 and 6.7 +/- 2.3 mg/dl (means +/- SD, n = 38) in terms of apo E and cholesterol, respectively. Apo E-rich HDL was increased strikingly in the sera from three patients with hepatobiliary diseases.
Assuntos
Apolipoproteínas E/sangue , Hepatite/sangue , Lipoproteínas HDL/sangue , Cirrose Hepática Biliar/sangue , Adulto , Precipitação Química , Doença Crônica , Sulfato de Dextrana , Feminino , Humanos , Magnésio , Pessoa de Meia-Idade , Ácido Fosfotúngstico , PolietilenoglicóisRESUMO
In a pilot study 5 females with primary biliary cirrhosis (PBC), histological stages I-III, were treated with methotrexate (7.5-15.0 mg by mouth weekly) for 15 months. Pruritus and fatigue decreased in 3 patients and cholestyramine could be reduced or discontinued. The concentration of alkaline phosphatase decreased significantly until the 6th month of treatment (P less than 0.002), but only after the methotrexate dosage had been increased to 15 mg weekly. However, the improvement in cholestasis parameters persisted until the end of the period of observation in only 3 patients in stages I and II. In only one case, initially in stage III with increased serum bilirubin concentration of 3.5 mg/dl, was there a change in the histological stage, to stage IV, after treatment. These preliminary results indicate that methotrexate can influence the symptoms and cholestasis enzymes in the early stages of PBC. Controlled studies should therefore only be conducted on anicteric patients in an early stage of the disease.
Assuntos
Cirrose Hepática Biliar/tratamento farmacológico , Metotrexato/uso terapêutico , Adulto , Fosfatase Alcalina/sangue , Bilirrubina/sangue , Colesterol/sangue , Resina de Colestiramina/uso terapêutico , Avaliação de Medicamentos , Feminino , Humanos , Cirrose Hepática Biliar/sangue , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Projetos Piloto , Fatores de TempoRESUMO
Serum bile acid classes have been studied in 15 patients with primary biliary cirrhosis in five patients with cholestasis, and in five patients who had cirrhosis without cholestatic features. Conjugated monohydroxy bile acids (12-35% serum total bile acids) were found in eight of 11 sera from patients with primary biliary cirrhosis, in sera from four patients with cholestasis but not in any of the five patients with cirrhosis. The glycine conjugates/taurine conjugates (G/T) ratio in eight of 11 patients with primary biliary cirrhosis and two of four patients with cholestasis was <1.0. Bile acid concentrations in seven patients with primary biliary cirrhosis were measured before and during cholestyramine therapy. Decreases in serum total bile acid concentrations were observed which were accompanied by small increases in the trihydroxy/dihydroxy ratio and also in the G/T ratio in six of the seven patients. No association was found between the concentration of any particular conjugated or free bile acid and the presence or absence of pruritus.
Assuntos
Ácidos e Sais Biliares/sangue , Cirrose Hepática Biliar/sangue , Colestase/sangue , Resina de Colestiramina/uso terapêutico , Glicina/sangue , Humanos , Hidroxilação , Cirrose Hepática Biliar/tratamento farmacológico , Testes de Função Hepática , Prurido/etiologia , Taurina/sangueRESUMO
A 45-yr-old woman with primary biliary cirrhosis, xanthomatosis, and marked hypercholesterolemia developed symptoms of the hyperviscosity syndrome on three separate occasions. On presentation, she had a plasma total cholesterol concentration of 53.40 mM (2065 mg/dl) and a relative serum viscosity of 2.9. Following three courses of plasma exchange in a 5-day period, the total cholesterol level decreased to 6.75 mM (261 mg/dl) and the viscosity to 1.3. The cutaneous xanthomata were markedly diminished 1 wk following plasma exchange. Despite therapy with colestipol (30 g/d), the hyperviscosity syndrome developed 147 days later. This cycle recurred again 137 days after colestipol was discontinued. Serum viscosity and total cholesterol concentration were highly correlated during the postexchange or accumulation phases (R = 0.95, 95% CI: 0.85, 0.98) and during the exchange or interventional phases (R = 0.95, 95% CI: 0.84, 0.99). Serum viscosity was less significantly correlated with total serum protein (R = 0.84; 95% CI: 0.55, 0.95) or with plasma triglyceride (R = 0.63; 95% CI: 0.26, 0.81). There were no significant correlations of red cell mass, plasma fibrinogen levels, or serum bile salts with viscosity. Subfractionation of plasma into lipoprotein classes showed 45% of total cholesterol in the lipoprotein X fraction and a presumptive slow alpha-lipoprotein species. It is postulated that both the hyperviscosity syndrome and rapid resolution of xanthomata in the patient may be attributable to the physiology of her abnormal lipoprotein particles.
Assuntos
Viscosidade Sanguínea , Hipercolesterolemia/sangue , Cirrose Hepática Biliar/sangue , Colesterol/sangue , Colesterol na Dieta/administração & dosagem , Colestipol/uso terapêutico , Terapia Combinada , Feminino , Humanos , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/patologia , Hipercolesterolemia/terapia , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/patologia , Cirrose Hepática Biliar/terapia , Pessoa de Meia-Idade , Troca Plasmática , Recidiva , Síndrome , Xantomatose/sangue , Xantomatose/diagnóstico , Xantomatose/patologia , Xantomatose/terapiaRESUMO
Both rat and human kidney nuclei exhibited time and pH dependent oxalate or histone-oxalate uptake which was inhibited by anion transport inhibitor, 4,4'-dithiocyanostilbene-2,2'-disulphonic acid. Sodium chloride had no effect. Nuclear membrane had oxalate binding at pH 7.4. Extraction of nuclear membrane by Triton-high salt mixture showed maximal oxalate binding activity with nuclear pore complex while nuclear lamin had no oxalate binding. The rat and human kidney nuclear pore complex showed oxalate binding of 144 and 220 pmoles/mg protein respectively. Subsequent purification of the protein on diethyl amino ethyl-Sephadex A 50 column and Sephadex G-200 column yielded 4-fold purification. The protein revealed a molecular weight of 205 kDa on SDS-PAGE. The protein was found to be saturable at 2 microM oxalate and had a Kd of 2.98 pM and a Bmax of 197 pmoles. Antibody for 205 kD was separated from primary biliary cirrhosis serum containing auto antibody against 205 kDa using affinity column chromatography. The oxalate binding activity as well as the nuclear uptake of oxalate or histone-oxalate were inhibited by its antibody.
Assuntos
Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Rim/metabolismo , Poro Nuclear/metabolismo , Proteínas de Transporte Nucleocitoplasmático , Animais , Autoanticorpos/metabolismo , Radioisótopos de Carbono , Núcleo Celular/metabolismo , Cromatografia de Afinidade , Detergentes/farmacologia , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Histonas/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Cinética , Cirrose Hepática Biliar/sangue , Masculino , Octoxinol/farmacologia , Oxalatos/sangue , Glicoproteínas da Membrana de Plaquetas/metabolismo , Ligação Proteica , Ratos , Ratos Wistar , Cloreto de Sódio/farmacologia , Fatores de TempoRESUMO
The natural history of pruritus in primary biliary cirrhosis (PBC) remains poorly defined. The aim of this investigation was to evaluate outcomes of pruritus in clinical trials for ursodeoxycholic acid (UDCA). In a UDCA-placebo trial begun in 1988 (n = 180), a 55% prevalence rate for pruritus was observed. Serum alkaline phosphatase level and Mayo risk score were independent risk factors for pruritus (P < 0.0001). Among placebo-treated patients (n = 91), the annual risks for development or improvement/resolution of pruritus were 27% and 23%, respectively. For UDCA-treated patients (n = 89), a trend toward improvement in pruritus was observed after 1 year compared to placebo (30% vs. 23%, P = 0.08) but not at 2 or 3 years. In a 3-dose UDCA trial begun in 1995 (n = 155), the overall prevalence of pruritus was significantly lower at 37% when compared to UDCA-placebo participants (P < 0.001). Baseline serum alkaline phosphatase level and Mayo risk score were again independent risk factors for pruritus (P < 0.0001). Among 13 (3.9%) patients with refractory pruritus, symptom resolution (n = 5) or improvement (n = 8) was associated with the use of oral rifampin (300 or 600 mg daily). Two patients treated with rifampin developed biochemical evidence for hepatotoxicity necessitating drug withdrawal. Although less prevalent among recently diagnosed individuals, more than one third of PBC patients develop pruritus. No significant risk reduction in developing pruritus with UDCA therapy was observed compared to placebo-treated patients. The long-term administration of rifampin for refractory pruritus is associated with occasional hepatotoxicity.