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1.
Neurotoxicology ; 20(4): 647-52, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10499363

RESUMEN

The hyperintense signal in the globus pallidus of cirrhotic patients on T1-weighted magnetic resonance (MR) imaging has been postulated to arise from deposition of paramagnetic manganese2+ (Mn). Intestinal absorption of both iron and Mn are increased in iron deficiency; iron deficiency may therefore increase susceptibility to Mn neurotoxicity. To investigate the relationships between MR signal abnormalities and Mn and Fe status, 21 patients with chronic liver disease were enrolled (alcoholic liver disease, 5; primary biliary cirrhosis, 9; primary sclerosing cholangitis, 3; hepatitis B virus, 2; hepatitis C virus, 1; alpha1-antitrypsin deficiency, 1). Signal hyperintensity in the pallidum on axial T1 weighted images (repetition time/evolution time: 500 ms/15 ms) was observed in 13 of 21 subjects: four patients had mild hyperintensity, three moderate, and six exhibited marked hyperintensity. Erythrocyte Mn concentrations were positively correlated with the degree of the MR hyperintensity (Kendall's tau-b=0.52, P<0.005). The log of erythrocyte Mn concentration was also inversely correlated with all measures of iron status: hemoglobin (Pearson's R=-0.73, P<0.0005); hematocrit (R=-0.62, P<0.005); serum Fe concentrations (R=-0.65, P<0.005); and TIBC saturation (R=-0.62, P<0.005). These findings confirm the association of Mn with the development of pallidal hyperintensity in patients with liver disease. We further found that iron deficiency is an exacerbating factor, probably because of increased intestinal absorption of Mn. We therefore recommend that patients with chronic liver disease avoid Mn supplements without concurrent iron supplementation.


Asunto(s)
Globo Pálido/fisiología , Hierro/metabolismo , Hepatopatías/metabolismo , Manganeso/metabolismo , Transducción de Señal/efectos de los fármacos , Adulto , Anciano , Eritrocitos/química , Femenino , Globo Pálido/patología , Humanos , Hierro/sangre , Deficiencias de Hierro , Imagen por Resonancia Magnética , Masculino , Manganeso/sangre , Persona de Mediana Edad , Factores de Tiempo
2.
Transfusion ; 34(6): 507-11, 1994 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7517586

RESUMEN

BACKGROUND: Bleeding complications frequently occur during orthotopic liver transplantation (OLT), particularly in patients with liver cirrhosis. Enhanced fibrinolytic activity in plasma was seen to play a key role in the development of the hemostatic disorder and of hemorrhages. Aprotinin, a serine protease inhibitor, has been used in the prevention and/or treatment of hyperfibrinolytic states. STUDY DESIGN AND METHODS: In the present study, the effect of aprotinin on bleeding complications and transfusion requirements was investigated in OLT patients with liver cirrhosis. Seven consecutive cirrhotic patients undergoing OLT were infused with aprotinin following an original protocol (1,000,000-KIU intravenous loading dose plus 500,000 kallikrein-inhibitory units per hour until skin closure). Seven previous cirrhotic OLT patients not receiving aprotinin were used as controls. RESULTS: In the treated group, a significant decrease in the number of transfused units of packed red cells (48.7%, p < 0.01), fresh-frozen plasma (24.4%, p < 0.05), platelets (35.9%, p < 0.01), and autologous blood (55.2%, p < 0.01) was observed as compared with the control group. Moreover, the mean length of operation was significantly shorter in the aprotinin-infused patients than in untreated patients (8.3 +/- 1.2 vs. 10.1 +/- 1.8 hours, respectively; p < 0.01)). In the aprotinin-treated group, the antifibrinolytic efficacy was confirmed by the lack of increase in D-dimer levels and decrease of fibrinogen in plasma; on the contrary, these changes were always seen in the group not receiving aprotinin. CONCLUSION: Infusion of aprotinin during OLT in cirrhotic patients can be recommended for the prevention of hyperfibrinolysis-triggered bleeding, thus reducing transfusion requirements. A possible protective effect on the primary nonfunction of the grafted liver is suggested.


Asunto(s)
Aprotinina/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Transfusión Sanguínea , Cirrosis Hepática/cirugía , Trasplante de Hígado , Adulto , Transfusión de Sangre Autóloga , Transfusión de Eritrocitos , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Fibrinógeno/metabolismo , Fibrinólisis , Humanos , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Plasma , Transfusión de Plaquetas
3.
Dig Dis Sci ; 36(5): 687-92, 1991 May.
Artículo en Inglés | MEDLINE | ID: mdl-2022171

RESUMEN

The changes in fructose-1-phosphate (F-1-P), intracellular pH, and ATP content of the liver after a fructose challenge were investigated noninvasively in vivo using phosphorus-31 nuclear magnetic resonance spectroscopy of dog liver four days after a portacaval shunt (PCS) with or without portal venous infusion of cyclosporin (CsA). The F-1-P metabolism was slower in PCS dogs (N = 2) as compared to either the normal (N = 2) or PCS + CsA-treated dogs (N = 3) (P less than 0.05). The intracellular pH temporarily decreased from 7.3 +/- 0.05 to 7.0 +/- 0.05 during the fructose challenge. The regenerative indexes were increased in the PCS + CsA group (P less than 0.01). These data obtained in vivo using 31P-NMR spectroscopy in the liver following a portacaval shunt, suggest that: (1) the energy status of the liver and the metabolic response to fructose are reduced in PCS compared to normal animals and (2) CsA treatment enhances the regenerative response of the liver and prevents the reduction in hepatic function associated with portacaval shunting.


Asunto(s)
Ciclosporinas/farmacología , Regeneración Hepática/efectos de los fármacos , Equilibrio Ácido-Base/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Animales , Perros , Metabolismo Energético/efectos de los fármacos , Fructosafosfatos/metabolismo , Espectroscopía de Resonancia Magnética , Fósforo , Derivación Portocava Quirúrgica
4.
Hepatology ; 13(4): 780-5, 1991 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-2010174

RESUMEN

The effect of cyclosporin A on the hepatic energy status and intracellular pH of the liver and its response to a fructose challenge has been investigated using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy in dogs. Three experimental groups were studied: (a) control dogs (n = 5), (b) dogs 4 days after the creation of an end-to-side portacaval shunt (n = 5), and (c) dogs 4 days after portacaval shunt and continuous infusion of cyclosporin A (4 mg/kg/day) by way of the left portal vein (portacaval shunt plus cyclosporin A, n = 5). The phosphorus-31 nuclear magnetic resonance spectra were obtained at 81 MHz using a Bruker BIOSPEC II 4.7-tesla nuclear magnetic resonance system equipped with a 40-cm horizontal bore superconducting solenoid. The phosphomonoesters (p less than 0.01), inorganic phosphate and ATP levels (p less than 0.05) were decreased significantly in portacaval shunt-treated and in portacaval shunt-plus-cyclosporin A-treated dogs compared with unshunted control dogs. After a fructose challenge (750 mg/kg body wt, intravenously), fructose-1-phosphate metabolism was reduced in portacaval shunt-treated dogs compared with either the normal or portacaval shunt-plus-cyclosporin A-treated dogs (p less than 0.05). Both portacaval shunt- and portacaval shunt-plus-cyclosporin A-treated dogs demonstrated a reduced decline in ATP levels after fructose infusion when compared with the controls (p less than 0.05). Immediately after the fructose challenge, the intracellular pH decreased from 7.30 +/- 0.03 to 7.00 +/- 0.05 in all animals (p less than 0.01) and then gradually returned to normal over 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Ciclosporinas/farmacología , Metabolismo Energético/efectos de los fármacos , Fructosa/metabolismo , Hígado/metabolismo , Espectroscopía de Resonancia Magnética , Derivación Portocava Quirúrgica , Adenosina Trifosfato/metabolismo , Animales , Perros , Femenino , Fructosa/farmacología , Fructosafosfatos/metabolismo , Hígado/patología , Fósforo/metabolismo , Valores de Referencia
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