RESUMEN
Humans use a family of more than 400 olfactory receptors (ORs) to detect odors, but there is currently no model that can predict olfactory perception from receptor activity patterns. Genetic variation in human ORs is abundant and alters receptor function, allowing us to examine the relationship between receptor function and perception. We sequenced the OR repertoire in 332 individuals and examined how genetic variation affected 276 olfactory phenotypes, including the perceived intensity and pleasantness of 68 odorants at two concentrations, detection thresholds of three odorants, and general olfactory acuity. Genetic variation in a single OR was frequently associated with changes in odorant perception, and we validated 10 cases in which in vitro OR function correlated with in vivo odorant perception using a functional assay. In 8 of these 10 cases, reduced receptor function was associated with reduced intensity perception. In addition, we used participant genotypes to quantify genetic ancestry and found that, in combination with single OR genotype, age, and gender, we can explain between 10% and 20% of the perceptual variation in 15 olfactory phenotypes, highlighting the importance of single OR genotype, ancestry, and demographic factors in the variation of olfactory perception.
Asunto(s)
Variación Genética , Genotipo , Percepción Olfatoria/genética , Receptores Odorantes/genética , Femenino , Humanos , MasculinoRESUMEN
The mechanisms underlying sweet taste in mammals have been elusive. Although numerous studies have implicated G proteins in sweet taste detection, the expected G protein-coupled receptors have not been found. Here we describe a candidate taste receptor gene, T1r3, that is located at or near the mouse Sac locus, a genetic locus that controls the detection of certain sweet tastants. T1R3 differs in amino acid sequence in mouse strains with different Sac phenotypes ('tasters' versus 'nontasters'). In addition, a perfect correlation exists between two different T1r3 alleles and Sac phenotypes in recombinant inbred mouse strains. The T1r3 gene is expressed in a subset of taste cells in circumvallate, foliate and fungiform taste papillae. In circumvallate and foliate papillae, most T1r3-expressing cells also express a gene encoding a related receptor, T1R2, raising the possibility that these cells recognize more than one ligand, or that the two receptors function as heterodimers.
Asunto(s)
Células Quimiorreceptoras/fisiología , Genes/fisiología , Gusto/genética , Alelos , Secuencia de Aminoácidos , Animales , Mapeo Cromosómico , Clonación Molecular , ADN/genética , Hibridación in Situ , Ratones , Ratones Endogámicos , Datos de Secuencia Molecular , Fenotipo , Polimorfismo Genético/genética , Papilas Gustativas/metabolismoRESUMEN
Predicting the activity of chemicals for a given odorant receptor is a longstanding challenge. Here the activity of 258 chemicals on the human G-protein-coupled odorant receptor (OR)51E1, also known as prostate-specific G-protein-coupled receptor 2 (PSGR2), was virtually screened by machine learning using 4884 chemical descriptors as input. A systematic control by functional in vitro assays revealed that a support vector machine algorithm accurately predicted the activity of a screened library. It allowed us to identify two novel agonists in vitro for OR51E1. The transferability of the protocol was assessed on OR1A1, OR2W1, and MOR256-3 odorant receptors, and, in each case, novel agonists were identified with a hit rate of 39-50%. We further show how ligands' efficacy is encoded into residues within OR51E1 cavity using a molecular modeling protocol. Our approach allows widening the chemical spaces associated with odorant receptors. This machine-learning protocol based on chemical features thus represents an efficient tool for screening ligands for G-protein-coupled odorant receptors that modulate non-olfactory functions or, upon combinatorial activation, give rise to our sense of smell.
Asunto(s)
Ácidos Grasos/metabolismo , Aprendizaje Automático , Proteínas de Neoplasias/agonistas , Receptores Acoplados a Proteínas G/agonistas , Animales , Evaluación Preclínica de Medicamentos , Ácidos Grasos/química , Humanos , Ligandos , Ratones , Modelos Moleculares , Proteínas de Neoplasias/química , Unión Proteica , Receptores Acoplados a Proteínas G/química , Receptores Odorantes/agonistas , Receptores Odorantes/químicaRESUMEN
BACKGROUND: 3-Isopropylmalate dehydrogenase (IPMDH) and isocitrate dehydrogenase (ICDH) belong to a unique family of bifunctional decarboxylating dehydrogenases. Although the ICDH dimer catalyzes its reaction under a closed conformation, known structures of the IPMDH dimer (without substrate) adopt a fully open or a partially closed form. Considering the similarity in the catalytic mechanism, the IPMDH dimer must be in a fully closed conformation during the reaction. A large conformational change should therefore occur upon substrate binding. RESULTS: We have determined the crystal structure of IPMDH from Thiobacillus ferrooxidans (Tf) complexed with 3-isopropylmalate (IPM) at 2.0 A resolution by the molecular replacement method. The structure shows a fully closed conformation and the substrate-binding site is quite similar to that of ICDH except for a region around the gamma-isopropyl group. The gamma group is recognized by a unique hydrophobic pocket, which includes Glu88, Leu91 and Leu92 from subunit 1 and Val193' from subunit 2. CONCLUSIONS: A large movement of domain 1 is induced by substrate binding, which results in the formation of the hydrophobic pocket for the gamma-isopropyl moiety of IPM. A glutamic acid in domain 1, Glu88, participates in the formation of the hydrophobic pocket. The C beta and C gamma atoms of Glu88 interact with the gamma-isopropyl moiety of IPM and are central to the recognition of substrate. The acidic tip of Glu88 is likely to interact with the nicotinamide mononucleotide (NMN) ribose of NAD+ in the ternary complex. This structure clearly explains the substrate specificity of IPMDH.
Asunto(s)
Oxidorreductasas de Alcohol/química , Thiobacillus/enzimología , 3-Isopropilmalato Deshidrogenasa , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Sitios de Unión/fisiología , Cristalografía por Rayos X , Malatos/química , Modelos Moleculares , Datos de Secuencia Molecular , NAD/química , Oxidorreductasas/química , Conformación Proteica , Pliegue de Proteína , Estructura Secundaria de Proteína , Alineación de Secuencia , Especificidad por SustratoRESUMEN
Hepatic artery thrombosis after orthotopic liver transplantation is a serious complication, especially in children. We report our experience with intensive anticoagulant therapy during and after living-related liver transplantation in pediatric recipients. Twenty-four patients between 5 months and 15 years of age were studied. The mean diameter of the anastomosed hepatic arteries was 2.7 mm. The anticoagulant therapy consisted of low-molecular-weight heparin, antithrombin III concentrates, prostaglandin E1, fresh frozen plasma, and a protease inhibitor. The profiles of the coagulation and fibrinolytic systems were monitored by measuring several parameters, including plasma levels of thrombin-antithrombin III complex, antithrombin III, plasmin-alpha 2 plasmin inhibitor complex, fibrin degradation product D-dimer, tissue type-plasminogen activator, and plasminogen activator inhibitor-1. Acceleration of the coagulation system and delayed recovery of the fibrinolytic system were observed during the early postoperative days. The plasma level of antithrombin III activity was maintained within the normal range by the administration of antithrombin III concentrates. None of the recipients developed hepatic artery thrombosis. Children have been reported to be at a greater risk of developing hepatic artery thrombosis than adults due to the small diameters of their hepatic arteries and the postoperative hypercoagulable state. We believe that the intensive anticoagulation therapy described in this study, the main concept of which is the early correction of imbalance between the coagulant and anticoagulant systems, could become a model for the prevention of hepatic artery thrombosis in pediatric liver transplantation patients.
Asunto(s)
Arteria Hepática , Trasplante de Hígado/efectos adversos , Trombosis/prevención & control , Adolescente , Anticoagulantes/uso terapéutico , Antitrombina III/análisis , Niño , Preescolar , Humanos , LactanteRESUMEN
Donor safety is the first consideration in living related liver transplantation. Left hemihepatectomy including the middle hepatic vein is a reasonable donor procedure for obtaining a large graft for living related liver transplantation. This procedure, however, needs to be modified in donors with hepatic venous variation. While carrying out donor hepatectomy, we encountered two cases showing a variant form of hepatic venous drainage comprising a thick middle hepatic vein draining segment 6 of the liver. This variation made it necessary to preserve the middle hepatic vein in the donor liver remnant. Failure to recognize such a variant would result in congestion in the remaining right liver of the donor. To guarantee donor safety, evaluation of the drainage area of the corresponding hepatic vein is a matter of great importance in donor hepatectomy.
Asunto(s)
Hepatectomía/métodos , Venas Hepáticas/diagnóstico por imagen , Venas Hepáticas/fisiología , Trasplante de Hígado , Donadores Vivos , Adolescente , Adulto , Femenino , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Seguridad , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: We describe a 1-year-old female who underwent living-related liver transplantation for biliary atresia and developed Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder. This disorder was resolved after withdrawal of immunosuppression therapy and administration of a high dose of acyclovir. METHODS: To quantify the extent of EBV activation and EBV load in peripheral blood, we measured the levels of EBV-infected peripheral lymphocytes by in situ hybridization (ISH) of EBV-encoded small mRNA 1 (EBER1). RESULTS: The decline in the number of EBER1-positive lymphocytes (from 362/50,000 mononuclear cells to 0/50,000) after treatment was in accord with the patient's clinical improvement. CONCLUSIONS: This finding showed that quantitative analysis of EBV-infected peripheral lymphocytes by ISH of EBER1 is very useful for monitoring the EBV load and response to treatment of patients with EBV-related disorders. Furthermore, ISH may become an important tool for the early diagnosis and prevention of life-threatening posttransplant lymphoproliferative disorder in posttransplant patients.
Asunto(s)
Infecciones por Herpesviridae/sangre , Trasplante de Hígado/efectos adversos , Linfocitos/virología , ARN Viral/sangre , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Femenino , Infecciones por Herpesviridae/etiología , Herpesvirus Humano 4/metabolismo , Humanos , Hibridación in Situ , Lactante , Trastornos Linfoproliferativos/sangre , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/virología , Linfocitos T Citotóxicos/inmunología , Trasplante Homólogo , Carga Viral , Activación ViralRESUMEN
Type II citrullinemia is an adult-onset hepatocerebral disease caused by a deficiency of argininosuccinate synthetase in liver. A 25-year-old Japanese man suddenly developed encephalopathy, showing disorientation and flapping tremor. Plasma concentrations of ammonia and citrulline were extremely high, and hepatic argininosuccinate synthetase activity was deficient. The patient's condition deteriorated rapidly in spite of intensive medications. Therefore, we performed a partial liver transplantation using a graft obtained from his healthy 61-year-old father. After surgery, his neurological symptoms soon disappeared and plasma levels of ammonia and citrulline were normalized within 3 months after operation. Type II citrullinemia is one fulminant form of various liver-based metabolic diseases, and immediate liver transplantation is necessary to rescue patients with this disease. As liver transplantation from cadaveric donor is still not possible in Japan, it seems justifiable to use living related partial liver transplantation for our patient.
Asunto(s)
Argininosuccinato Sintasa/deficiencia , Encefalopatía Hepática/cirugía , Trasplante de Hígado , Adulto , Errores Innatos del Metabolismo de los Aminoácidos/cirugía , Humanos , Hígado/enzimología , Masculino , Donantes de Tejidos , Resultado del TratamientoRESUMEN
BACKGROUND: We describe the case of a man with intrahepatic arterioportal fistulae located in the left lobe, whose left lateral segment was transplanted into his son who was suffering from severe acute hepatitis B. METHODS: A male infant with severe acute hepatitis B was considered to be a candidate for liver transplantation. The father was willing to be the donor. Preoperative evaluation of the donor revealed intrahepatic arterioportal fistulae, however, duplex ultrasonography showed normograde portal blood flow. A living-related liver transplantation was performed. RESULTS: The postoperative course for both the donor and recipient was uneventful. The recipient is free of recurrent hepatitis B and has normograde portal blood flow. CONCLUSIONS: The present case suggests that there may be a symptomless population with intrahepatic arterioportal fistulae, which cause various degrees of disruption of the portal blood flow. Duplex ultrasonography might be helpful in the evaluation of candidates for liver donation.
Asunto(s)
Fístula Arteriovenosa/diagnóstico por imagen , Arteria Hepática/anomalías , Hepatitis B/cirugía , Trasplante de Hígado , Donadores Vivos , Vena Porta/anomalías , Adulto , Estudios de Seguimiento , Arteria Hepática/diagnóstico por imagen , Humanos , Lactante , Circulación Hepática , Trasplante de Hígado/patología , Donadores Vivos/provisión & distribución , Imagen por Resonancia Magnética , Masculino , Monitoreo Intraoperatorio , Sistema Porta , Vena Porta/diagnóstico por imagen , Radiografía , Factores de Tiempo , Ultrasonografía Doppler DúplexRESUMEN
BACKGROUND: An essential prerequisite for living related partial liver transplantation is to perform donor hepatectomy with minimal risk while preserving graft viability. This article describes a safe method of donor hepatectomy that was used for five patients who underwent living related liver transplantation. METHODS: Liver parenchymal transection was performed by the selective vascular occlusion technique in four patients, and interruption of the blood supply to the left medial segment was carried out along the right side of the umbilical portion before parenchymal division in the other patient. RESULTS: These procedures resulted in insignificant intraoperative blood loss, for which no banked blood or blood derivatives were transfused. The postoperative course for each of the five donors was uneventful, and excellent graft viability was verified by the fact that the five recipients showed a good immediate postoperative course without marked increases in the serum activities of liver enzymes. CONCLUSIONS: We believe that the operative risk of living related donor hepatectomy is minimal if it is performed by experienced liver surgeons with the present procedures.
Asunto(s)
Hepatectomía/métodos , Fallo Hepático/cirugía , Trasplante de Hígado , Donantes de Tejidos , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Niño , Salud de la Familia , Humanos , Japón , Fallo Hepático/sangre , MasculinoRESUMEN
BACKGROUND: Because graft arteries are smaller and shorter in living-related liver transplantation (LRLT) than in whole or reduced-size liver transplantation from cadavers, arterial reconstruction is thought to be one of the critical points for success. METHODS: Thirty LRLT patients were classified into two groups: those in whom all graft hepatic arteries were reconstructed (group A), and those whom only had some were reconstructed (group B). In group A 17 patients had a single hepatic artery and three had two hepatic arteries. In group B the thickest one of several arteries was reconstructed, but the others were ligated after pulsatile back-bleeding from their cut stumps had been confirmed. The clinical results were compared between the two groups. RESULTS: Neither arterial thrombosis nor liver dysfunction related to the arterial blood supply was observed during the postoperative course. One case of bile leakage and two cases of bile duct stenosis occurred in group A. No significant difference was noted in the postoperative values of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase between the two groups. Overall patient and graft survival was 90%. CONCLUSIONS: Although several hepatic arteries may supply the potential allograft in LRLT, it is not always necessary to reconstruct all of them.
Asunto(s)
Arteria Hepática/cirugía , Trasplante de Hígado , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , MasculinoRESUMEN
To estimate the effects of the prostacyclin analog (OP-41483) on normothermic liver ischemia and reperfusion injury, saline (Group 1, N = 8), heparin (group 2, N = 8, 100 u/kg) or OP-41483 (group 3, N = 8, 400 ng/kg/min) was infused intravenously for 30 min before and after liver ischemia in rats. There were no significant differences in survival, or transaminase at 30 min after reperfusion among the three groups. Hepatic vessel flow and tissue flow were measured for the first 30 min after reperfusion. Hepatic tissue flow increased for the first 30 min after reperfusion in the group 3 rats, but not in the groups 2 and 3 rats. There were significant differences in hepatic tissue flow between the groups 1 and 3 rats at 20 min (p < 0.05), as well as significant differences between the groups 1 and 3 rats (p < 0.01) and the groups 1 and 2 rats (p < 0.05) at 30 min after reperfusion. There were no significant differences in total hepatic inflow among the three groups. Our data suggest that OP-41483 exerts beneficial effects by improving the microcirculation and increasing the effective hepatic blood flow in the ischemically injured liver after reperfusion.
Asunto(s)
Epoprostenol/análogos & derivados , Isquemia/tratamiento farmacológico , Hígado/irrigación sanguínea , Inhibidores de Agregación Plaquetaria/farmacología , Daño por Reperfusión/tratamiento farmacológico , Animales , Epoprostenol/farmacología , Femenino , Hígado/efectos de los fármacos , Hígado/enzimología , Ratas , Ratas Wistar , Flujo Sanguíneo Regional/efectos de los fármacos , Tasa de SupervivenciaRESUMEN
A new lymphoma cell line, designated SUBL, was established from a Japanese patient with Epstein-Barr virus (EBV)-associated lymphoma, which developed during FK 506 therapy after liver transplantation. This cell line has undergone 80 passages over a period of 22 months. The cultured cells were positive for CD19, CD20, CD21, CD22, CD23, and HLA-DR, and negative for CD10 and surface immunoglobulins. Immunoglobulin gene analysis revealed rearrangements of JH and JK. T-cell antigens or T-cell receptor gene rearrangements were not observed on the cell line. The SUBL cells were positive for Epstein-Barr virus nuclear antigen (EBNA). The EBV genome was detected in the original tissue and the cell line by the in situ hybridization method. These data indicate that this cell line represents the B-cell lineage at a pre-B-cell stage. SUBL cells showed successful heterotransplantation to mice with severe combined immunodeficiency (SCID). Chromosomal analysis revealed the karyotype 46,XY,t(2;3)(p11;q27). Molecular studies showed that c-myc, N-myc, and bcl-2 were not rearranged. This cell line will provide a useful in vitro system to study the relationship between chromosomal abnormalities and the activation of cellular oncogenes.
Asunto(s)
Transformación Celular Viral/genética , Cromosomas Humanos Par 2/ultraestructura , Cromosomas Humanos Par 3/ultraestructura , Herpesvirus Humano 4/genética , Linfoma de Células B/genética , Linfoma de Células B/microbiología , Translocación Genética , Células Tumorales Cultivadas/microbiología , Animales , Antígenos CD , Antígenos Virales de Tumores , Linfoma de Burkitt/genética , Linfoma de Burkitt/microbiología , Niño , Reordenamiento Génico , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inmunofenotipificación , Hibridación in Situ , Trasplante de Hígado/efectos adversos , Masculino , Ratones , Ratones SCID , Trasplante de Neoplasias , Derrame Pleural/citología , Neoplasias del Colon Sigmoide/microbiología , Tacrolimus/efectos adversos , Células Tumorales Cultivadas/inmunología , Células Tumorales Cultivadas/trasplanteRESUMEN
A 14-year-old girl with blood type B with late onset hepatic failure (LOHF) of unknown cause has survived through living-related liver transplantation (LRLT). No hepatitis virus, including HAV, HBV, HCV, and HGV, was positive at the onset of LOHF. Autoimmune hepatitis was thought to be the cause because of positive results for serum anti-nuclear antibody at 80 times dilution and elevated gamma-globulin, but treatment with glucocorticoid did not suppress the progressive hepatic failure. Supportive therapy, including pulse therapy with 1g methylprednisolone for 3 days, ursodesoxycholic acid, branched-chain amino acid, and azathioprine did not resolve the hepatic failure. She was treated by repeated plasmapheresis and plasma absorption for 10 months, and then received the left lobe of her mother's liver. (Her mother's blood type was AB). The patient had been well, being treated with tacrolimus and prednisolone, although the serum titer of anti-blood type B antibody was high just after LRLT and mild liver dysfunction continued for more than 3 years after LRLT. Follow-up biopsy 3 years after LRLT revealed chronic hepatitis and progression to liver cirrhosis. Re-transplantation is now under consideration; the patient is now aged 19 years.
Asunto(s)
Incompatibilidad de Grupos Sanguíneos , Fallo Hepático/cirugía , Trasplante de Hígado , Sistema del Grupo Sanguíneo ABO/inmunología , Adolescente , Biopsia , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Hepatitis Crónica/complicaciones , Hepatitis Crónica/diagnóstico , Humanos , Hígado/patología , Cirrosis Hepática/etiología , Fallo Hepático/etiología , Fallo Hepático/patología , Pruebas de Función Hepática , Trasplante de Hígado/inmunología , Factores de Tiempo , Trasplante Heterólogo/inmunologíaRESUMEN
The important features of extended lateral segmentectomy to obtain a partial liver graft comprising the left lateral segment and the left half of the medial segment are described with special reference to anatomical variation of the hepatic venous system. Ramification patterns of the hepatic vein tributaries around the juncture of the major hepatic veins with the inferior vena cava are delineated before starting liver resection, using intraoperative ultrasound. The left medial vein draining the left part of the medial segment is recognized close to the confluence of the middle and left hepatic veins. This tributary flows into the left hepatic vein in the majority of cases, but sometimes into the middle hepatic vein. The liver transection line is established in order to obtain the graft, including the drainage area of the left medial vein. Intraoperative ultrasound is indispensable for identifying the left medial vein in extended lateral segmentectomy.
Asunto(s)
Hepatectomía/métodos , Trasplante de Hígado , Hígado/diagnóstico por imagen , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Periodo Intraoperatorio , Hígado/irrigación sanguínea , Hígado/cirugía , Circulación Hepática , Trasplante de Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , UltrasonografíaRESUMEN
3-Isopropylmalate dehydrogenase was purified to homogeneity from the acidophilic autotroph Thiobacillus thiooxidans. The native enzyme was a dimer of molecular weight 40,000. The apparent K(m) values for 3-isopropylmalate and NAD+ were estimated to be 0.13 mM and 8.7 mM, respectively. The optimum pH for activity was 9.0 and the optimum temperature was 65 degrees C. The properties of the enzyme were similar to those of the Thiobacillus ferrooxidans enzyme, expect for substrate specificity. T. thiooxidans 3-isopropylmalate dehydrogenase could not utilize malate as a substrate.
RESUMEN
Living related liver transplantation was performed in five cases between June 1989 and July 1991 at Shinshu University Hospital. All of the donors were fathers of the patients and blood type was identical in each case. All of them were discharged from the hospital 2 weeks after hepatectomy without any complications. They started to work 2 months after surgery. Four recipients are surviving but one died. Three are enjoying daily life 17 months after LT in case 1, 5 months after LT in case 4, and 4 months after LT in case 5. Case 2 is still in the hospital 14 months after LT. Advantages of LRLT we noted were (1) cases can be performed totally electively and allow full preparation for the family and the transplant team, (2) primary graft nonfunction has not been observed to date, and (3) 38 patients received the chance of liver transplantation in their own country, which under current legislation would not otherwise have been possible. Disadvantages of LRLT were (1) partial hepatectomy was performed in healthy persons, and (2) retransplantation is difficult.
Asunto(s)
Trasplante de Hígado/métodos , Donantes de Tejidos , Atresia Biliar/cirugía , Niño , Femenino , Rechazo de Injerto , Hepatectomía , Humanos , Lactante , Cirrosis Hepática/cirugía , Trasplante de Hígado/inmunología , Masculino , Factores de TiempoRESUMEN
The authors present details of their initial experience with use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) for preventing neutropenia caused by hypersplenism, and, possibly, for reducing the risk of postoperative infections in pediatric liver transplant recipients. Seven patients with end-stage liver disease, three of whom had severe hypersplenism, underwent living related liver transplantation (LRLT). The rhG-CSF was administered to the latter three patients. Peripheral neutrophil counts decreased immediately after reperfusion (to 1500 +/- 300/microL) in the three patients, and returned to normal with use of rhG-CSF 3 to 10 days after transplantation. The dosage was adjusted to maintain peripheral leukocyte and granulocyte counts above 5,000/microL and 2,000/microL, respectively. This initial clinical trial showed that rhG-CSF administration restores the leukocyte counts of patients who have hypersplenism, without any significant adverse effects, and that rhG-CSF holds promise for reducing the risk of infections after liver transplantation.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Hiperesplenismo/complicaciones , Trasplante de Hígado , Neutropenia/terapia , Niño , Femenino , Humanos , Lactante , Recuento de Leucocitos , Hepatopatías/cirugía , Masculino , Neutropenia/sangre , Neutropenia/etiología , Proteínas Recombinantes/uso terapéuticoRESUMEN
Crigler-Najjar disease (CN) type I is characterized by persistent unconjugated hyperbilirubinemia from birth. The male patient here was diagnosed with this disease as a neonate and had been treated by phototherapy. At age 16 he suddenly developed generalized convulsions, followed by impaired cognitive function. The serum level of bilirubin was extremely high (total bilirubin: 41.7 mg/dl) and there were no other detectable causes responsible for the metabolic encephalopathy. He received bilirubin adsorption therapy several times, and the bilirubin encephalopathy improved in response to the fall in the serum level of bilirubin. After this he underwent a successful liver transplantation in Australia, and recovery of his mental faculties was satisfactory. Within the subsequent 3 years epileptic abnormal discharges on the electroencephalogram disappeared. Phototherapy alone can not prevent the rise in the serum level of bilirubin in adolescent or adult patients with CN type I, therefore such patients tend to experience life-threatening bilirubin encephalopathy. To save patients with the acute onset type of bilirubin encephalopathy, sufficient bilirubin adsorption followed by liver transplantation appears to be the most recommended therapeutic approach.
Asunto(s)
Bilirrubina/farmacocinética , Síndrome de Crigler-Najjar/complicaciones , Kernicterus/terapia , Trasplante de Hígado , Adsorción , Adulto , Humanos , Masculino , Inducción de Remisión , Índice de Severidad de la Enfermedad , Sobrevivientes , Factores de TiempoRESUMEN
A 60-year-old woman was admitted to our hospital for repeated consciousness disturbance. Blood examination showed hyperammonemia, and plasma amino acid analysis revealed a marked increase in the citrulline level. To establish a diagnosis, a percutaneous needle biopsy of the liver was performed. The determination of the urea cycle enzyme activities revealed a selective marked decrease in argininosuccinate synthetase activity, indicating the final diagnosis of type II citrullinemia. The mean survival period of this disease after the appearance of symptoms has been reported as 26.4 months, and most conservative treatments are not effective. We performed a living related partial liver transplantation. Over the subsequent 13-month follow-up, the patient's condition has remained fairly good.