RESUMEN
BACKGROUND: Animal studies on acetaminophen toxicity suggest that chronic alcohol intake affects the outcome adversely, whereas acute alcohol intake seems protective. Few clinical data are available. METHODS: We studied 209 consecutive patients with single-dose acetaminophen overdose. The combined influence of independent variables (gender, age, dose, delay to antidote treatment, chronic and acute alcohol intake and nomogram risk group) on dependent variables (death, development of hepatic encephalopathy and biochemical liver markers) was studied using multiple or logistic regression analysis. RESULTS: Fifty-seven (27.3%) patients had chronic alcohol intake and 45 (21.5%) patients had acute alcohol intake. Forty-four (21.1%) patients developed hepatic coma and 20 (43.5%) of these patients died. Chronic alcohol intake was significantly and independently associated with the development of hepatic coma, with a lower prothrombin index, lower platelet count, higher creatinine and higher bilirubin. The relative risks for hepatic coma and death were 5.3 (95% confidence interval, 2.2-12.4) and 1.4 (95% confidence interval, 0.5-3.9), respectively, in the chronic alcohol intake group compared with the no chronic alcohol intake group. Acute alcohol intake was not significantly associated with any of the dependent variables studied. CONCLUSIONS: Chronic alcohol intake enhances acetaminophen hepatotoxicity, whereas acute alcohol intake does not affect the clinical course.
Asunto(s)
Acetaminofén/envenenamiento , Intoxicación Alcohólica/complicaciones , Alcoholismo/complicaciones , Sobredosis de Droga/complicaciones , Femenino , Encefalopatía Hepática/inducido químicamente , Encefalopatía Hepática/mortalidad , Humanos , Modelos Logísticos , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Low admission values of the actin scavenger Gc-globulin are associated with an adverse outcome in acetaminophen (paracetamol) overdose. This prospective longitudinal study including 84 patients with acetaminophen overdose characterizes the temporal profile of Gc-globulin during the entire length of hospitalization. Serum Gc-globulin (total, actin bound, and free) levels and actin-complex ratio were measured on admission and every 12 hours until discharge. In 32 patients without hepatotoxicity (non-HEPTOX group; peak transaminase levels < 1,000 U/L), total and free Gc-globulin levels and complex ratio remained within normal range during hospitalization. Among 52 patients with hepatotoxicity (HEPTOX group; peak transaminase levels > 1,000 U/L), 15 patients had hepatic encephalopathy (HE), and 37 patients did not. In these 2 groups, total and free Gc-globulin levels decreased to 97 and 50 mg/L and 148 and 86 mg/L, respectively (normal mean, 340 and 299 mg/L), the nadir occurring at 72 hours postoverdose. Complex ratio peaked at 60 hours at levels more than 3-fold greater than normal. Conversely, bound Gc-globulin remained within normal levels for all patients throughout the observation period. At day 2, a total Gc-globulin cutoff value of less than 120 mg/L correctly predicted HE in 75%, and a value greater than 120 mg/L correctly predicted the absence of HE in 91% of patients. In conclusion, Gc-globulin is severely stressed in patients with hepatotoxicity. Extreme values occurred at 60 to 72 hours postoverdose, a period in which Gc-globulin protection against actin toxicity may be inadequate. A total Gc-globulin level less than 120 mg/L on day 2 is a good predictor of later HE. Bound Gc-globulin is maintained at constant levels independent of total Gc-globulin levels, suggesting a balanced upregulation of the removal of bound Gc-globulin even under conditions with increased actin release.
Asunto(s)
Acetaminofén/efectos adversos , Analgésicos no Narcóticos/efectos adversos , Proteína de Unión a Vitamina D/sangre , Actinas/metabolismo , Adulto , Enfermedad Hepática Inducida por Sustancias y Drogas , Sobredosis de Droga , Femenino , Encefalopatía Hepática/sangre , Encefalopatía Hepática/inducido químicamente , Encefalopatía Hepática/diagnóstico , Humanos , Hepatopatías/sangre , Hepatopatías/diagnóstico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Valores de Referencia , Factores de Tiempo , Proteína de Unión a Vitamina D/metabolismoRESUMEN
BACKGROUND: A low serum level (< 100 mg/L) of the actin-scavenger Gc-globulin is a prognostic marker of non-survival in fulminant hepatic failure (FHF). It is unknown whether decreased production or increased consumption (or both) is responsible for the low Gc-globulin levels. METHODS: Ten patients with FHF and four patients with acute or chronic liver disease (AOCLD) with hepatic encephalopathy (HE) grades II-IV were included. Eight patients with cirrhosis (chronic liver disease, CLD) without HE served as controls. Total, free, and actin-bound Gc-globulin were measured in samples from an artery, a central vein, and a hepatic vein. In 12 patients (9 FHF, 3 AOCLD), concentrations were measured before and after high volume plasmapheresis (HVP). RESULTS: Total Gc-globulin was reduced to 21%, 40%, and 43% of the normal level in the FHF, AOCLD, and CLD groups, respectively, whereas bound Gc-globulin was within normal range in all patients. The Gc:actin complex ratio was increased 3.8, 2.5, and 1.9-fold compared with normal levels. Total, free, and bound serum Gc-globulin levels did not differ among arterial, systemic venous, or hepatic venous blood. Total Gc-globulin rose to >100 mg/L in all patients after HVP, whereas bound Gc-globulin remained unchanged. The Gc-globulin production rate in FHF and AOCLD patients was increased to 4.1 +/- 1.3 mg/min compared to literature values of 0.6 mg/min in healthy individuals. The estimated half-life of total Gc-globulin was shorter in the patients compared to healthy individuals (127 +/- 56 min and 870 min, respectively). CONCLUSIONS: Gc-globulin levels were reduced in patients with FHF and AOCLD because a 7-fold increase of Gc-globulin production rate could not compensate for the accelerated clearance. Bound Gc-globulin was maintained within normal levels in all circumstances studied, indicating a possible regulatory role of this parameter in the clearance of actin.
Asunto(s)
Encefalopatía Hepática/metabolismo , Cirrosis Hepática/metabolismo , Fallo Hepático/metabolismo , Proteína de Unión a Vitamina D/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Semivida , Encefalopatía Hepática/sangre , Humanos , Cirrosis Hepática/sangre , Fallo Hepático/sangre , Masculino , Proteína de Unión a Vitamina D/sangreRESUMEN
AIM: The aim of this investigation was to identify which part of a dose mesalazine is acetylated by enzymes in the gut wall during the absorption process, and which part by the liver enzymes after absorption. METHOD: This study was based on data from four bioequivalence studies of different formulations of tablets (gastro-resistant single dose 500 mg (n = 24) and prolonged-release tablets (single dose 1000 mg, n = 18; multiple dose 1000 mg t.i.d. six days n = 28), suppositories (single 500 mg dose, n = 24) and a study with two i.v. administrations of 100 and 250 mg mesalazine (n = 6). In total, 200 administrations were carried out and plasma concentration-time curves obtained and analyzed. There was a large variability in the absorption of mesalazine for all formulations. The plasma concentration-time curves of parent drug and metabolite acetylmesalazine run nearly parallel, independent of the formulation and the dose. Plasma and urine mesalazine and acetylmesalazine concentrations were determined according to validated methods using HPLC analysis with coulometric or mass-spectrometric detection. RESULTS: As a result of the large variations in release and absorption of mesalazine in the pharmaceutical formulations and administrations, it was possible to demonstrate that acetylation occurs in the gut wall and in the liver. By comparing oral and rectal data to intravenous data, it was possible to indicate where (and to what extent) acetylation occurs in the gut wall, in the liver, or both. Rectal administration of a mesalazine suppository and intravenous administration results in hepatic acetylation. Oral administrations of mesalazine results in both gut wall and hepatic acetylation. Acetylation by the gut wall amounts to 30% of the dose for gastroresistant tablets and to 40% of the dose for prolonged-release tablets.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacocinética , Mucosa Intestinal/metabolismo , Hígado/metabolismo , Mesalamina/farmacocinética , Acetilación , Área Bajo la Curva , Estudios Cruzados , Humanos , Mesalamina/administración & dosificaciónRESUMEN
BACKGROUND: Paracetamol overdose may cause hepatic encephalopathy (HE). This condition demands specialized care and, in some instances, liver transplantation evaluation. No model is available for predicting HE. We aimed to set up and validate a model for predicting the occurrence of HE in paracetamol overdose. METHODS: Prospectively, 161 patients with single-dose paracetamol overdose and no HE (defined as hepatic coma grade II or more) on admission were studied during a 26-month period. Patients admitted during the first 13-month period constituted a learning set to construct a model to predict the occurrence of HE. Patients admitted in the second 13-month period constituted the validation set. Serial biochemical variables (measured twice daily), the time line after the overdose, and demographic data were used for univariate testing, and significant factors were assessed in various multiple logistic regression analyses. RESULTS: Thirty-two patients (20%), 15 in the first period and 17 in the second, developed HE grade II. The best model (the highest chi-square) for HE included: log10 (hours from overdose to antidote treatment), log10 (plasma coagulation factors on admission), and platelet count hours from overdose (chi-square = 41.2, P < 0.00001). In the validation set 88% (confidence interval (CI), 64%-99%) of the patients who developed HE were correctly predicted by the constructed model, whereas 90% (CI, 79%-96%) of the patients in the non-HE group were correctly predicted. CONCLUSIONS: The constructed model for predicting HE in paracetamol overdose proved sensitive and accurate in the validation set and should be valuable for transferring high-risk patients to a liver intensive care unit/transplantation facility.
Asunto(s)
Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Encefalopatía Hepática/inducido químicamente , Modelos Estadísticos , Adolescente , Adulto , Anciano , Niño , Sobredosis de Droga , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Probabilidad , Estudios ProspectivosRESUMEN
Serum levels of the actin scavenger Gc-globulin (group-specific component, vitamin D-binding protein), a member of the albumin multigene family, are decreased in severe liver disease but have not been evaluated in relation to liver transplantation. We measured Gc-globulin and Gc-globulin-actin complex ratio daily for 2 weeks after transplantation in 17 patients with end-stage liver disease. Before transplantation, Gc-globulin levels were significantly less in the patients than in healthy controls (235 +/- 106 v 340 +/- 35 mg/L, respectively; P<.001), whereas complex ratio level was in the normal range. Five patients (group N) had pretransplantation Gc-globulin values within the normal range (mean +/- 2 SD), and 12 patients had subnormal values (group S). In group N, mean Gc-globulin levels posttransplantation remained stable at a lower level than before transplantation but still within normal range. In this group, cold ischemia time correlated inversely with Gc-globulin levels on day 2 (r = -0.88; P <.05). In group S, normal mean levels were reached at a mean of 11 days after transplantation. However, almost half these patients had subnormal Gc-globulin levels at day 14. Complex ratio levels remained normal in the study period in both groups. Prothrombin index levels (plasma coagulation factors II, VII, and X) were identical in both groups and returned to normal 7 days posttransplantation, whereas plasma albumin levels were less than normal in both groups and further decreased after transplantation. In conclusion, the maintenance (group N) or reestablishment (group S) of serum Gc-globulin to normal levels occurred in the early posttransplantation course in the same time frame as the prothrombin index. Gc-globulin synthesis seems unrelated to albumin synthesis. A prolonged cold ischemia time may cause reduced Gc-globulin levels early after transplantation.
Asunto(s)
Actinas/metabolismo , Fallo Hepático/cirugía , Trasplante de Hígado/fisiología , Proteína de Unión a Vitamina D/sangre , Adulto , Criopreservación , Factor VII/análisis , Factor X/análisis , Femenino , Humanos , Fallo Hepático/metabolismo , Trasplante de Hígado/métodos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Protrombina/análisis , Albúmina Sérica/análisis , Albúmina Sérica/biosíntesis , Albúmina Sérica/genética , Factores de Tiempo , Proteína de Unión a Vitamina D/biosíntesis , Proteína de Unión a Vitamina D/genéticaRESUMEN
OBJECTIVES: In patients with multiple trauma, actin released from damaged cells may cause severe circulatory disturbance due to thrombi formation. The aim of this study was to evaluate serum concentrations of the actin scavenger, Gc-globulin, in relation to the severity of injury and outcome. DESIGN: Prospective, longitudinal, observational study. SETTING: Trauma center at a university hospital. PATIENTS: Twelve patients with multiple trauma, consecutively included, according to defined criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum Gc-globulin concentrations were measured at the time of admission and daily thereafter for 1 wk or until death. In all patients, the Gc-globulin concentration was significantly low (p < .0001), and the proportion of Gc-globulin bound to actin was already increased compared with normal values (p < .0001) by the time of hospital arrival. There was an inverse correlation between the mean concentration of serum Gc-globulin in the first week after trauma and the Injury Severity Score (r = -0.72, p < .05). Surviving patients had a significantly (p < .05) higher concentration of serum Gc-globulin in the first week after trauma compared with nonsurvivors. CONCLUSIONS: Serum concentrations of Gc-globulin were significantly low in trauma patients. The reduction took place within 60 mins after injury. Because the normal half-life of Gc-globulin is almost 48 hrs, our observations suggest a marked consumption of Gc-globulin immediately after the trauma. This finding could be the first clinical evidence that Gc-globulin plays a role in the systemic inflammatory response syndrome after trauma. This result is supported by the finding that lack of Gc-globulin was related to nonsurvival and the severity of the trauma.
Asunto(s)
Traumatismo Múltiple/sangre , Proteína de Unión a Vitamina D/sangre , Actinas/sangre , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Traumatismo Múltiple/mortalidad , Estudios Prospectivos , Estadísticas no Paramétricas , Tasa de Supervivencia , Sobrevivientes/estadística & datos numéricos , Factores de Tiempo , Índices de Gravedad del TraumaRESUMEN
OBJECTIVE: To evaluate the association between admission serum concentrations of the actin-scavenger, Gc-globulin, and the subsequent development of multiple organ failure in patients with fulminant hepatic failure. DESIGN: Retrospective study. SETTING: A hepatologic intensive care unit. PATIENTS: Seventy-nine patients with hepatic encephalopathy grade 3 or 4. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum admission concentrations of both total and nonactin-complexed (free) Gc-globulin were determined. The development of cardiovascular failure, renal failure, pulmonary failure, intracranial hypertension, and infections were recorded in each patient. Both total and free Gc-globulin values were significantly lower in the patients, compared with normal controls. The Gc-globulin values were significantly reduced in patients who subsequently developed cardiovascular failure (p < .01), intracranial hypertension (p < .001), and infections (p < .001), compared with those patients who did not. No differences were found between patients with and without pulmonary or renal failure. Patients with total Gc-globulin values in the lowest quintile had on average 2.6 organ failures, whereas patients with Gc-globulin concentrations in the highest quintile had 0.9 organ failures. The corresponding figures for the lowest and highest quintiles of free Gc-globulin were 3.0 and 1.1 organ failures, respectively. Both total and free Gc-globulin were inversely correlated to the number of organ failures (p < .005 in both cases). Patients with multiple organ failure (> or = 2 organ failures) had significantly reduced Gc-globulin values compared with patients without multiple organ failure (p < .0001). CONCLUSIONS: In patients with fulminant hepatic failure, the lowest admission Gc-globulin concentrations were associated with the subsequent development of cardiovascular failure, intracranial hypertension, and infections. Lack of Gc-globulin correlated significantly with the development of multiple organ failure and may be pathogenetically involved in this condition.
Asunto(s)
Encefalopatía Hepática/sangre , Encefalopatía Hepática/complicaciones , Insuficiencia Multiorgánica/etiología , Proteína de Unión a Vitamina D/sangre , Proteína de Unión a Vitamina D/deficiencia , Adolescente , Adulto , Anciano , Niño , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Infecciones/etiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Seudotumor Cerebral/etiología , Reproducibilidad de los Resultados , Insuficiencia Respiratoria/etiología , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Prophylactic treatment with ursodeoxycholic acid (UDCA) has been reported to reduce the incidence of acute rejection after liver transplantation compared with historical controls. We investigated this in a prospective, randomized, placebo-controlled multicenter study. METHODS: Fifty-four liver transplant patients were allocated to the UDCA treatment group (15 mg/kg/day), and 48 patients were allocated to the placebo group. Trial medicine was started on the first postoperative day and was given for 3 months. Follow-up was for 12 months. Treatment was stratified for adults with chronic liver disease (n=77), adults with acute liver failure (n=10), and children (n=15). RESULTS: The frequency of patients with acute rejection was 65% in the UDCA treatment group and 68% in the placebo group. The frequency of steroid-resistant rejection was similar in both groups. The probability of acute rejection, analyzed according to the intention-to-treat policy with Kaplan-Meier analysis, was similar in both treatment groups. No significant differences were found in patient survival and graft survival probabilities. For the biochemical markers of cholestasis, only gamma-glutamyltransferase was significantly improved after 2 months of UDCA treatment. CONCLUSIONS: The initial optimistic report of a beneficial effect of prophylactic treatment with UDCA on acute rejection after liver transplantation was not confirmed in this controlled study.
Asunto(s)
Inmunosupresores/uso terapéutico , Trasplante de Hígado/inmunología , Ácido Ursodesoxicólico/uso terapéutico , Adolescente , Adulto , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Bilirrubina/sangre , Niño , Preescolar , Ciclosporina/sangre , Método Doble Ciego , Femenino , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Factores de Tiempo , gamma-Glutamiltransferasa/sangreAsunto(s)
Antiinflamatorios no Esteroideos/farmacocinética , Enfermedades Inflamatorias del Intestino/metabolismo , Mucosa Intestinal/metabolismo , Mesalamina/farmacocinética , Preparaciones de Acción Retardada , Humanos , Mesalamina/administración & dosificación , Mesalamina/metabolismo , Sulfasalazina/farmacocinéticaRESUMEN
Gc-globulin scavenges actin liberated from necrotic cells. We measured serum Gc-globulin and the degree of complexing with monomeric actin (complex ratio) in the initial phase of paracetamol (acetaminophen) intoxication and related this to the severity of liver necrosis and the clinical course. In eighteen patients with paracetamol intoxication serial measurements of serum Gc-globulin and complex ratio were determined from admission and every three hours thereafter. Eight patients developed hepatic encephalopathy (HE) and two of them died. On admission all patients had significantly reduced serum Gc-globulin levels compared to normal individuals, and patients with HE had significantly lower values than patients without HE. All patients with HE had at least three samples, where Gc-globulin was below 120 mg/l (35% of normal). Complex ratio on admission did not differ significantly in the patients with and those without HE. The peak complex ratio was higher in patients with HE than in patients without HE, and three of four patients with peak complex ratio above 75% had HE. In conclusion, Gc-globulin levels were found to be decreased in patients with paracetamol intoxication; this decrease correlated with the most severe sign of liver dysfunction, HE. Serum Gc-globulin below 120 mg/l and peak complex ratios above 75% may be critical values.
Asunto(s)
Acetaminofén/envenenamiento , Analgésicos/envenenamiento , Globulinas/análisis , Intoxicación/sangre , Proteína de Unión a Vitamina D/análisis , Adulto , Femenino , Encefalopatía Hepática/sangre , Encefalopatía Hepática/inducido químicamente , Humanos , Masculino , PronósticoRESUMEN
Gc-globulin scavenges actin released from necrotic hepatocytes to the extracellular space. In 77 patients with fulminant hepatic failure (FHF) (excluding patients treated with liver transplantation), admission levels of serum Gc-globulin and degree of complexing with monomeric actin (complex ratio) were determined to evaluate their predictive values in relation to survival/nonsurvival. Gc-globulin levels were significantly reduced in 47 nonsurvivors, compared with 30 survivors (96 +/- 71 mg/L vs. 169 +/- 101 mg/L, P < .001), whereas the complex ratio in nonsurvivors did not differ significantly from that of survivors. Gc-globulin levels were significantly lower in 59 patients with non-acetaminophen-induced FHF, compared with 18 patients with acetaminophen-induced FHF (P < .01). Using a cutoff level of serum Gc-globulin of 100 mg/L, a lesser value correctly predicted nonsurvival in 79 percent of patients with non-acetaminophen-induced FHF, whereas a higher value predicted survival in 60 percent. In patients with acetaminophen-induced FHF, nonsurvival was correctly predicted in 100 percent of patients and survival in 53 percent. In comparison, the King's College Hospital (KCH) criteria correctly predicted nonsurvival and survival in 69 percent and 57 percent, respectively, of the same non-acetaminophen-induced FHF patients and in 60 percent and 38 percent, respectively, of the acetaminophen-induced FHF patients. Thus, in our study population, the predictive properties of Gc-globulin were in the same range as the KCH criteria. An advantage of Gc-globulin is that it gives an estimate of the outcome already on admission. Acute liver transplantation should be considered in FHF patients with Gc-globulin less than 100 mg/L.
Asunto(s)
Encefalopatía Hepática/sangre , Proteína de Unión a Vitamina D/sangre , Acetaminofén/efectos adversos , Adulto , Anciano , Femenino , Encefalopatía Hepática/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , PronósticoAsunto(s)
Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/prevención & control , Cirrosis Hepática/complicaciones , Várices Esofágicas y Gástricas/tratamiento farmacológico , Várices Esofágicas y Gástricas/etiología , Hemorragia Gastrointestinal/etiología , Antagonistas de Hormonas/uso terapéutico , Humanos , Cirrosis Hepática/cirugía , Trasplante de Hígado , Derivación Portosistémica Quirúrgica , Escleroterapia , Somatostatina/uso terapéutico , Vasopresinas/uso terapéuticoRESUMEN
BACKGROUND: Omeprazole is effective in the treatment of reflux oesophagitis, and it is important to determine the lower dose limit with still appropriate clinical efficacy. METHODS: Patients with endoscopic oesophagitis grade 1-4 (N = 220) were randomized to double-blind treatment with 20 mg or 40 mg omeprazole daily for 4-8 weeks. Those healed after this initial treatment phase were re-randomized to double-blind treatment with 20 mg omeprazole daily (n = 67), 10 mg omeprazole daily (n = 68), or placebo (n = 33) for 6 months. Remission was defined as the absence of any endoscopic sign of oesophagitis. RESULTS: Healing rates were increased with 40 mg omeprazole, the therapeutic gain compared with the 20-mg dose being 15% after 4 and 8 weeks. The proportion of patients in remission after 6 months was 59% with 20 mg omeprazole, 35% with 10 mg omeprazole, and 0% with placebo. CONCLUSION: Maintenance treatment with 10 mg omeprazole can prevent recurrence of oesophagitis in about one-third of patients with all grades of oesophagitis, and 20 mg omeprazole in about twice as many.
Asunto(s)
Antiulcerosos/administración & dosificación , Esofagitis Péptica/tratamiento farmacológico , Omeprazol/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antiulcerosos/uso terapéutico , Intervalos de Confianza , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Esofagitis Péptica/etiología , Esofagitis Péptica/fisiopatología , Femenino , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/uso terapéutico , Recurrencia , Análisis de Regresión , Resultado del TratamientoRESUMEN
OBJECTIVES: To describe serum Gc-globulin and the extent to which it complexes with monomeric actin in the initial phase of acetaminophen (Paracetamol) intoxication and to relate this to the severity of liver necrosis and the clinical course. PATIENTS AND METHODS: Serial measurements of Gc-globulin and the proportion of Gc-globulin complexed to G-actin (complex ratio) were made on admission and every 3 h thereafter in eighteen consecutive patients with acetaminophen intoxication. Eight patients developed hepatic encephalopathy (HE) and two died. RESULTS: On admission, all patients had significantly reduced serum Gc-globulin levels compared with normal individuals (P < 0.0001); patients with HE had significantly lower values than patients without HE (P < 0.001). Gc-globulin levels in the two patients who died did not differ from those in patients who survived hepatic encephalopathy. Fourty-four of 52 serum samples with Gc-globulin levels below 120 mg/l were from patients with encephalopathy (all eight of these patients provided at least three samples). The complex ratio on admission did not differ significantly between patients with and those without HE and fluctuated considerably during the observation period. The peak complex ratio was, however, higher in patients with HE than in patients without HE (P < 0.01), and three of four patients with peak complex ratios above 75% had HE. In addition, the mean complex ratio was greater in the two patients who died than in those who survived HE (P < 0.05). CONCLUSION: Gc-globulin levels were decreased in individuals suffering from acetaminophen intoxication; this decrease correlated with the most severe sign of liver dysfunction, HE. Serum Gc-globulin levels below 120 mg/l and peak complex ratios above 75% may be critical values. However, as a result of considerable fluctuations in the complex ratio, serial measurements are needed to evaluate the Gc-globulin complexing capacity.
Asunto(s)
Acetaminofén/envenenamiento , Actinas/sangre , Analgésicos no Narcóticos/envenenamiento , Encefalopatía Hepática/inducido químicamente , Proteína de Unión a Vitamina D/sangre , Adulto , Estudios de Casos y Controles , Femenino , Encefalopatía Hepática/sangre , Humanos , Inmunoelectroforesis , Masculino , Intoxicación/sangre , Factores de TiempoRESUMEN
In the period 1989-1994 eight patients, who were intoxicated with the mushrooms Amanita phalloides (death cap) or Amanita virosa (deadly agaric) were treated at a Department of Hepatology. All patients had had a symptom free period of more than eight hours before the onset of gastrointestinal symptoms; these symptoms lasting in many cases for several days. All patients had biochemical signs of hepatocellular damage and three patients developed hepatic encephalopathy, fulfilling the criteria for fulminant hepatic failure (FHF). Two died and one patient underwent successful urgent liver transplantation. ALL FHF patients had a prothrombin index below 10% and increased creatine. Antidote treatment with penicillin and silibinine should be given promptly on suspicion of Amanita intoxication and should not await biochemical parameters. Transferral to a hepatological department with access to liver transplantation should be considered if abnormal biochemical liver function develops.
Asunto(s)
Intoxicación por Setas/terapia , Adulto , Anciano , Amanita , Dinamarca , Femenino , Unidades Hospitalarias , Humanos , Masculino , Persona de Mediana Edad , Intoxicación por Setas/diagnóstico , Intoxicación por Setas/metabolismo , Estudios RetrospectivosRESUMEN
BACKGROUND: Different concentrations of immunoglobulin G (IgG) subclass-producing cells in the mucosa of patients with ulcerative colitis and Crohn's disease have previously been described. METHODS: To evaluate serum concentration of IgG subclasses as a tool for diagnosis and disease activity in chronic inflammatory bowel disease, we compared serum concentrations of IgG, IgA, IgM, and immunoglobulin subclasses IgG1, IgG2, IgG3, and IgG4 by means of the radial immunodiffusion technique in 66 patients with ulcerative colitis and in 68 patients with Crohn's disease of different clinical stages. Erythrocyte sedimentation rate, haemoglobin, and serum concentrations of albumin and orosomucoid were also determined. RESULTS: The serum IgG1 concentration in patients with ulcerative colitis was 8.0 g/l significantly higher than in patients with Crohn's disease (6.8 g/l) (p < 0.005), whereas the serum IgG2 concentration in patients with Crohn's disease was 3.8 g/l, significantly increased compared with patients with ulcerative colitis (3.1 g/l) (p < 0.004). In patients with active ulcerative colitis the serum IgA level (2.03 g/l) was significantly lower than that in the patients with less active disease (2.74 g/l) (p < 0.03). No significant differences in serum concentrations of total IgG, IgG3, IgG4, and IgM were found between groups of patients with ulcerative colitis and Crohn's disease. The differences observed in IgG1, IgG2, and IgA concentrations, however, are small. CONCLUSIONS: The serum concentrations of IgG, IgA, IgM, and IgG subclasses are of little value in the diagnostic procedures in individual patients and are not superior to conventional laboratory tests such as sedimentation rate and serum concentrations of orosomucoid and albumin.
Asunto(s)
Colitis Ulcerosa/inmunología , Enfermedad de Crohn/inmunología , Inmunoglobulina G/sangre , Adulto , Sedimentación Sanguínea , Colitis Ulcerosa/sangre , Enfermedad de Crohn/sangre , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Orosomucoide/análisis , Albúmina Sérica/análisisRESUMEN
Oxidative damage is thought to play an important role in ischemia/reperfusion injury, including the outcome of transplantation of the liver and intestine. We have investigated oxidative DNA damage after combined transplantation of the liver and small intestine in 5 pigs. DNA damage was estimated from the urinary excretion of the repair product 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). In the first 1-3 hr after reperfusion of the grafts, 8-oxodG excretion was increased 2.9-fold (1.7-4.1; 95% confidence intervals; P < 0.05). A control experiment included sham surgery with clamping of the suprarenal inferior caval vein in 2 pigs during steady state infusion of 8-oxodG. While the caval vein was clamped, the urinary excretion of 8-oxodG was almost blocked, whereas after removal of the clamp, the excretion returned to and did not exceed the preclamp levels. In a separate experiment with 2 pigs, the elimination of injected 8-oxodG was shown to adhere to first-order kinetics with a clearance and a terminal elimination half-life of approximately 4 ml min-1 kg-1 and 2 1/2 hr, respectively. The injected dose was completely excreted into the urine within 4 hr. It is concluded that substantial oxidative damage to DNA results from reperfusion of transplanted small intestine and liver in pigs, as estimated from the readily excreted repair product 8-oxodG.
Asunto(s)
Daño del ADN , Intestino Delgado/trasplante , Trasplante de Hígado , Daño por Reperfusión/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Desoxiguanosina/análogos & derivados , Desoxiguanosina/orina , Intestino Delgado/irrigación sanguínea , Intestino Delgado/metabolismo , Hígado/irrigación sanguínea , Hígado/metabolismo , Estrés Oxidativo , PorcinosRESUMEN
High volume plasmapheresis has previously been found to improve neurological statuses in patients with fulminant hepatic failure. We investigated the relationship between the neurological status and cerebral blood flow velocity (Vmean) during high volume plasmapheresis in 18 consecutive patients (ten females and eight males) with fulminant hepatic failure, with a mean age of 43 (range 9 to 57) years. The mean arterial pressure (MAP) and intracranial pressure (ICP) were also recorded. A total of 16% of body weight was exchanged with fresh frozen plasma per day. Thirty-six plasma exchanges wer performed with a median of 2 (range 1 to 8) per patient. Eleven of the patients survived (61%), nine after liver transplantation. Following the first high volume plasmapheresis, the coma score improved from 6 (1-8) to 2 (0-8) (p < 0.05), Vmean increased from 40 (14-152) to 62 (16-186) cm s-1 (p < 0.05), and MAP from 72 (35-118) to 94 (47-138) mmHg (p < 0.05). The intracranial pressure (ICP) was monitored and remained unchanged in nine patients whereas the cerebral perfusion pressure (MAP minus ICP) increased in the surviving group from 55 (40-74) to 80 (50-91) mmHg (p = 0.07) in contrast to no changes in the non survival group. In conclusion this study suggests that the neurological status, may improve during high volume plasmapheresis as MAP and Vmean increase the cerebral oxygen delivery.