RESUMO
This paper describes a method to construct a standardized health care resource use database. Billing and clinical data were analyzed for 916 patients who received liver transplantations at three medical centers over a 4-year period. Data were checked for completeness by assessing whether each patient's bill included charges covering specified dates and for specific services, and for accuracy by comparing a sample of bills to medical records. Detailed services were matched to a standardized service list from one of the centers, and a single price list was applied. For certain services, clinical data were used to estimate service use or, if a match was not possible, adjusted charges for the services were used. Twenty-three patients were eliminated from the database because of incomplete resource use data. There was very good correspondence between bills and medical records, except for blood products. Direct matches to the standardized service list accounted for 69.3% of services overall; 9.4% of services could not be matched to the standardized service list and were thus adjusted for center and/or time period. Clinical data were used to estimate resource use for blood products, operating room time, and medications; these estimations accounted for 21.3% of services overall. A database can be constructed that allows comparison of standardized resource use and avoids biases due to accounting, geographic, or temporal factors. Clinical data are essential for the creation of such a database. The methods described are particularly useful in studies of the cost-effectiveness of medical technologies.
Assuntos
Coleta de Dados/métodos , Interpretação Estatística de Dados , Bases de Dados Factuais , Recursos em Saúde/estatística & dados numéricos , Transplante de Fígado/estatística & dados numéricos , Contabilidade/normas , Análise Custo-Benefício , Honorários e Preços/estatística & dados numéricos , Recursos em Saúde/economia , Humanos , Transplante de Fígado/economia , Prontuários Médicos/normas , Análise Multivariada , Reprodutibilidade dos Testes , Estados UnidosRESUMO
The frequency with which florid duct lesions are seen in needle-biopsy specimens of the liver was assessed in patients with primary biliary cirrhosis (PBC) enrolled in a 2-year randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) versus placebo. Paired biopsy specimens obtained at entry and after 2 years on medication were reviewed blindly and mostly simultaneously by a panel of 5 hepatopathologists who, earlier, had characterized the florid duct lesion, which has been well described in the pathology literature. Florid duct lesions at entry were identified in approximately 36%. Patients with earlier disease showed florid duct lesions much more frequently than those with more advanced disease. The prevalence of florid duct lesions in 60 patients receiving placebo medication fell from 38.3% to 21.7%, P =. 025, over the period of 2 years. The prevalence of florid duct lesions also decreased in the 55 patients receiving UDCA, from 32.7% to 18.2%, P =.046. The prevalences of these lesions in the placebo and UDCA patients at entry and at 2 years were not significantly different from each other. The findings suggest that UDCA does not prevent ongoing bile duct destruction in patients with PBC. Instead, they support the impression that UDCA exerts its beneficial effects by protecting against the consequences of bile duct destruction.
Assuntos
Ductos Biliares/efeitos dos fármacos , Cirrose Hepática Biliar/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico , Ductos Biliares/patologia , Método Duplo-Cego , Humanos , Cirrose Hepática Biliar/patologiaRESUMO
Bile acid composition in fasting duodenal bile was assessed at entry and at 2 years in patients with primary biliary cirrhosis (PBC) enrolled in a randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) (10-12 mg/kg/d) taken as a single bedtime dose. Specimens were analyzed by a high-pressure liquid chromatography method that had been validated against gas chromatography. Percent composition in bile (mean +/- SD) for 98 patients at entry for cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA), and ursodeoxycholic (UDCA) acids, respectively, were 57.4 +/- 18.6, 31.5 +/- 15.5, 8.0 +/- 9.3, 0.3 +/- 1.0, and 0.6 +/- 0.9. Values for CA were increased, whereas those for CDCA, DCA, LCA, and UDCA were decreased when compared with values in normal persons. Bile acid composition of the major bile acids did not change after 2 years on placebo medication. By contrast, in patients receiving UDCA for 2 years, bile became enriched with UDCA on average to 40.1%, and significant decreases were noted for CA (to 32.2%) and CDCA (to 19.5%). No change in percent composition was observed for DCA and LCA. Percent composition at entry and changes in composition after 2 years on UDCA were similar in patients with varying severity of PBC. In patients whose bile was not enriched in UDCA (entry and placebo-treated specimens), CA, CDCA, DCA, and the small amount of UDCA found in some of these specimens were conjugated to a greater extent with glycine (52%-64%) than with taurine (36%-48%). Treatment with UDCA caused the proportion of all endogenous bile acids conjugated with glycine to increase to 69% to 78%, while the proportion conjugated with taurine (22%-31%) fell (P <.05). Administered UDCA was also conjugated predominantly with glycine (87%).
Assuntos
Ácidos e Sais Biliares/análise , Bile/metabolismo , Cirrose Hepática Biliar/tratamento farmacológico , Cirrose Hepática Biliar/metabolismo , Ácido Ursodesoxicólico/uso terapêutico , Ácido Quenodesoxicólico/análise , Ácido Cólico/análise , Cromatografia Gasosa/métodos , Cromatografia Líquida de Alta Pressão/métodos , Ácido Desoxicólico/análise , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Ácido Litocólico/análise , Masculino , Pessoa de Meia-Idade , Placebos , Análise de Regressão , Reprodutibilidade dos Testes , Fatores de Tempo , Ácido Ursodesoxicólico/administração & dosagemRESUMO
CONTEXT: Liver transplantation is among the most costly of medical services, yet few studies have addressed the relationship between the resources utilized for this procedure and specific patient characteristics and clinical practices. OBJECTIVE: To assess the association of pretransplant patient characteristics and clinical practices with hospital resource utilization. DESIGN: Prospective cohort of patients who received liver transplants between January 1991 and July 1994. SETTING: University of California, San Francisco; Mayo Clinic, Rochester, Minn; and the University of Nebraska, Omaha. PATIENTS: Seven hundred eleven patients who received single-organ liver transplants, were at least 16 years old, and had nonfulminant liver disease. MAIN OUTCOME MEASURE: Standardized resource utilization derived from a database created by matching all services to a single price list. RESULTS: Higher adjusted resource utilization was associated with donor age of 60 years or older (28% [$53813] greater mean resource utilization; P=.005); recipient age of 60 years or older (17% [$32795]; P=.01); alcoholic liver disease (26% [$49596]; P=.002); Child-Pugh class C (41% [$67 658]; P<.001); care from the intensive care unit at time of transplant (42% [$77833]; P<.001); death in the hospital (35% [$67 076]; P<.001); and having multiple liver transplants during the index hospitalization (154% increase [$474 740 vs $186 726 for 1 transplant]; P<.001). Adjusted length of stay and resource utilization also differed significantly among transplant centers. CONCLUSIONS: Clinical, economic, and ethical dilemmas in liver transplantation are highlighted by these findings. Recipients who were older, had alcoholic liver disease, or were severely ill were the most expensive to treat; this suggests that organ allocation criteria may affect transplant costs. Clinical practices and resource utilization varied considerably among transplant centers; methods to reduce variation in practice patterns, such as clinical guidelines, might lower costs while maintaining quality of care.
Assuntos
Recursos em Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Transplante de Fígado/economia , Avaliação de Processos e Resultados em Cuidados de Saúde , Alocação de Recursos , Adulto , Fatores Etários , California , Feminino , Alocação de Recursos para a Atenção à Saúde , Recursos em Saúde/economia , Preços Hospitalares , Mortalidade Hospitalar , Hospitalização/economia , Humanos , Unidades de Terapia Intensiva/economia , Unidades de Terapia Intensiva/estatística & dados numéricos , Modelos Lineares , Hepatopatias/economia , Hepatopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Minnesota , Análise Multivariada , Nebraska , Seleção de Pacientes , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
Chronic infection with the hepatitis C virus (HCV) is the most common reason for liver transplantation. We examined the results of laboratory tests for HCV on a cohort of patients who received a liver transplant between 1990 and 1994 at three large centers. Seven hundred twenty-two recipients and 604 donors were tested for antibody to HCV (anti-HCV) using a second-generation enzyme-linked immunoassay (EIA-2), followed by recombinant immunoblot (RIBA-2) and HCV RNA confirmation by reverse-transcription polymerase chain reaction (RT-PCR) (with genotyping and viral quantification). Diagnosis of posttransplantation infection required detection of serum HCV RNA that could be genotyped by sequencing or was repeatedly positive despite being unsequenceable. Twenty-five percent of transplantation candidates were seropositive for anti-HCV. Approximately 86% of anti-HCV-positive, 93% of RIBA-positive, and 97% of HCV RNA-positive candidates developed infection after transplantation. Pretransplantation HCV RNA was superior to RIBA-2 for predicting posttransplantation infection. Whereas HCV genotype was identified in nearly all candidates and changed little after transplantation, serum viral levels rose markedly after transplantation. Fifteen donors were either anti-HCV- or HCV RNA-positive. Recipients of grafts from donors with HCV RNA all developed infection, whereas infection was not detected in recipients of grafts from donors with anti-HCV but without detectable HCV RNA. The rate of new infection fell significantly (P =.02) after the introduction of EIA-2 screening of blood. Donor and candidate markers for HCV predict posttransplantation infection.
Assuntos
Hepatite C/sangue , Transplante de Fígado/efeitos adversos , Estudos de Coortes , Previsões , Genótipo , Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Estudos Prospectivos , RNA Viral/sangue , Recidiva , Reprodutibilidade dos Testes , Testes Sorológicos , Doadores de Tecidos , Transplante , Carga ViralRESUMO
Hepatic allograft rejection remains an important problem following liver transplantation, and, indeed, complications related to the administration of immunosuppressive therapy remain a predominant cause of posttransplantation morbidity and mortality. The Liver Transplantation Database (LTD) was used to study a cohort of 762 consecutive adult liver transplantation recipients and determined the incidence, timing, and risk factors for acute rejection. We also evaluated the impact of histological severity of rejection on the need for additional immunosuppressive therapy and on patient and graft survival. Four hundred ninety (64%) of the 762 adult liver transplantation recipients developed at least one episode of rejection during a median follow-up period of 1,042 days (range, 336-1,896 days), most of which occurred during the first 6 weeks after transplantation. Multivariate analysis revealed that recipient age, serum creatinine, aspartate transaminase (AST) level, presence of edema, donor/recipient HLA-DR mismatch, cold ischemic time, and donor age were independently associated with the time to acute rejection. An interesting observation was that the histological severity of rejection was an important prognosticator: the use of antilymphocyte preparations was higher, and the time to death or retransplantation was shorter, for patients with severe rejection. Findings from this study will assist in decision-making for the use of immunosuppressive regimens and call into question whether complete elimination of all rejection or alloreactivity is a desirable goal in liver transplantation.
Assuntos
Rejeição de Enxerto , Transplante de Fígado , Adolescente , Adulto , Idoso , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Incidência , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Transplante HomólogoRESUMO
BACKGROUND: The average age of liver transplant recipients has increased steadily during the last decade. The effects of recipient age on outcome of liver transplantation were evaluated in a large prospective database. METHODS: A total of 735 adult recipients of single-organ liver transplants for nonfulminant liver disease enrolled in a large prospective database between 1990 and 1994 were analyzed for associations of patient age with outcomes. Patients were categorized into two groups: younger being <60 and older being > or = 60 years of age. RESULTS: Older liver transplant recipients were more likely to be female, white, and have the diagnoses of primary biliary cirrhosis or cryptogenic cirrhosis than younger recipients, who were more likely to have the diagnosis of alcoholic liver disease. Disease severity was similar between the two groups. After transplantation, the durations of stay in the intensive care unit and hospital were longer for older than for younger transplant recipients, but episodes of acute rejection were less frequent. The quality of life at 1 year was similar among older and younger recipients. Patient survival was lower for older than for younger recipients (81% vs. 90% at 1 year; P=0.004), whereas graft survival was not different (80% vs. 85% at 1 year; P=0.163). The excess mortality among older recipients was largely due to nonhepatic causes, including infectious, cardiac, and neurological diseases occurring within 6 months after transplantation. CONCLUSIONS: Although patient survival was significantly lower among liver transplant recipients above the age of 60 years, the excess mortality was due to nonhepatic, largely age-related problems. The overall success of liver transplantation and improvement in quality of life for older recipients is excellent.
Assuntos
Transplante de Fígado/estatística & dados numéricos , Adulto , Fatores Etários , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de SobrevidaRESUMO
Ethanol consumption slows down the rate of hepatic protein catabolism. The present study was conducted to determine whether ethanol consumption, given by voluntary (pair) feeding or by intragastric administration, affected the peptidase activities of the proteasome in rat liver. Rats were pair-fed liquid diets containing either ethanol or isocaloric maltose-dextrin. A separate group of animals was intragastrically infused continuously with similar liquid diets containing either ethanol or isocaloric dextrose. Crude liver homogenates and their cytosolic fractions were assayed for their chymotrypsin-like (Cht-L), trypsin-like (T-L), and peptidyl-glutamyl-peptide hydrolase (PGPH) activities, using specific fluorogenic peptides as substrates. Voluntary ethanol feeding did not affect the three peptidase activities of the proteasome. However, intragastric ethanol administration caused a 35% to 40% decline in the Cht-L and the T-L activities, but did not significantly change the PGPH activity. The lower peptidase activities in cytosol samples from intragastrically ethanol-fed rats were not restored to control levels by overnight dialysis, nor by the inclusion of low levels of sodium dodecyl sulfate (SDS) or of 0.5 mmol/L adenosine triphosphate (ATP) in the proteasome assay mixture. Immunoblot analyses using anti-rat liver proteaseome exhibited equal levels of immunoreactive proteasome subunits in livers of control and ethanol-fed rats. Similar results were obtained when blots were probed with antibody made specifically against the proteasome subunit, LMP-7. The results indicate that intragastric, but not voluntary, ethanol consumption differentially affects the separate catalytic activities of the proteasome without affecting its steady-state levels. Such changes may be related to the degree of ethanol-induced oxidative stress.
Assuntos
Quimotripsina/metabolismo , Cisteína Endopeptidases/metabolismo , Etanol/administração & dosagem , Hidrolases/metabolismo , Fígado/enzimologia , Complexos Multienzimáticos/metabolismo , Tripsina/metabolismo , Animais , Ingestão de Líquidos , Etanol/farmacologia , Intubação Gastrointestinal , Fígado/efeitos dos fármacos , Masculino , Complexo de Endopeptidases do Proteassoma , Ratos , Ratos WistarRESUMO
BACKGROUND: Poor graft function early after liver transplantation is an important cause of morbidity and mortality. We defined early allograft dysfunction (EAD) using readily available indices of function and identified donor, graft, and pretransplant recipient factors associated with this outcome. METHODS: This study examined 710 adult recipients of a first, single-organ liver transplantation for non-fulminant liver disease at three United States centers. EAD was defined by the presence of at least one of the following between 2 and 7 days after liver transplantation: serum bilirubin >10 mg/dl, prothrombin time (PT) > or =17 sec, and hepatic encephalopathy. RESULTS: EAD incidence was 23%. Median intensive care unit (ICU) and hospital stays were longer for recipients with EAD than those without (4 days vs. 3 days, P = 0.0001; 24 vs. 15 days, P = 0.0001, respectively). Three-year recipient and graft survival were worse in those with EAD than in those without (68% vs. 83%, P = .0001; 61% vs. 79%, P = 0.0001). A logistic regression model combining donor, graft, and recipient factors predicted EAD better than models examining these factors in isolation. Pretransplant recipient elevations in PT and bilirubin, awaiting a graft in hospital or ICU, donor age > or =50 years, donor hospital stay >3 days, preprocurement acidosis, and cold ischemia time > or =15 hr were independently associated with EAD. CONCLUSION: Recipients who develop EAD have longer ICU and hospital stays and greater mortality than those without. Donor, graft, and recipient risk factors all contribute to the development of EAD. Results of these analyses identify factors that, if modified, may alter the risk of EAD.
Assuntos
Falência Hepática/diagnóstico , Testes de Função Hepática , Transplante de Fígado , Complicações Pós-Operatórias/diagnóstico , Adolescente , Adulto , Bilirrubina/sangue , Cuidados Críticos , Feminino , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/mortalidade , Humanos , Tempo de Internação/estatística & dados numéricos , Falência Hepática/mortalidade , Transplante de Fígado/fisiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Obesity is a concern in the long-term management of patients following liver transplantation, yet the risk of obesity and the factors that influence its development have not been well defined. We evaluated posttransplantation weight change among a cohort of 774 adults who had their height and weight recorded before liver transplantation at three major centers. Obesity was defined as a body mass index (BMI) of at least 30 kg/m2. Weight at transplantation was adjusted by the amount of ascites removed. Mean BMI increased from 24.8 kg/m2 pretransplantation to 27.0 kg/m2 in the first posttransplantation year, to 28.1 kg/m2 in the second year, and very little with subsequent observation. Among 320 patients who were not obese before transplantation, 21.6% became obese within 2 years after transplantation. On evaluation of numerous potential donor and pretransplantation risk factors, greater recipient BMI, greater donor BMI, and being married were found to be predictors of subsequent obesity (P < .05). Posttransplantation predictors of obesity included absence of acute cellular rejection, higher cumulative prednisone dose in the second year, and cyclosporine-based immunosuppression, although only rejection and prednisone dose remained predictors on multivariate analysis. Despite the marked weight gain after transplantation, prevalence of obesity at 2 years was only slightly greater than in the general US population. Obesity occurred commonly after liver transplantation, sometimes with a striking gain in weight. In addition to BMI at transplantation, donor BMI, marital status, occurrence of acute rejection, and prednisone dose affected the incidence of obesity.
Assuntos
Transplante de Fígado/efeitos adversos , Obesidade/etiologia , Aumento de Peso , Adulto , Idoso , Índice de Massa Corporal , Estudos de Coortes , Ciclosporina/efeitos adversos , Feminino , Glucocorticoides/efeitos adversos , Rejeição de Enxerto/complicações , Rejeição de Enxerto/tratamento farmacológico , Humanos , Imunossupressores/efeitos adversos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prednisona/efeitos adversos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
We compared the effects of acute and chronic ethanol administration on the activity and synthesis of tyrosine aminotransferase (TAT) in rat liver. In acute experiments, chow-fed rats received a single dose of either ethanol (6 g/kg body wt.) or saline. In chronic studies, rats were pair-fed liquid diets containing either ethanol (36 % of calories) or isocaloric maltose-dextrin for 6-8 weeks. In rats acutely fed ethanol, the relative rate of TAT synthesis was more than twofold higher than in saline-treated controls. In rats subjected to chronic ethanol administration, both the TAT activity and synthesis rate were the same as in pair-fed controls, but both these parameters in the two groups were equal to those in animals given acute ethanol acutely. These findings indicate that whereas acute ethanol administration was associated with a stimulation of TAT synthesis, long-term ethanol administration was not. The data suggest that ethanol itself does not directly induce TAT. Rather, enzyme synthesis is regulated by one or more endogenous secondary effector(s) whose production is influenced differently by acute or chronic ethanol feeding.
Assuntos
Etanol/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/enzimologia , Tirosina Transaminase/metabolismo , Animais , Dieta , Etanol/farmacologia , Técnicas de Imunoadsorção , Insulina/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Tirosina/sangue , Tirosina Transaminase/biossíntese , Redução de PesoRESUMO
BACKGROUND & AIMS: Organ donors are a potential source of transmissible disease after transplantation. The aim of this study was to evaluate the risk of acquiring hepatitis B among transplantation recipients of livers from donors without serum hepatitis B surface antigen (HBsAg) but with antibody to hepatitis B core antigen (anti-HBc). METHODS: The transplantation experience of four centers between 1989 and 1994 was reviewed. Recipients of livers from 674 donors were considered informative for hepatitis B virus transmission. RESULTS: Hepatitis B developed in 18 of 23 recipients of livers from anti-HBc-positive donors (78%) compared with only 3 of 651 recipients of anti-HBc-negative donor livers (0.5%) (P < 0.0001). HBsAg persisted in all recipients with donor-related hepatitis B. Liver histology showed chronic hepatitis of moderate severity in 2 of 13 recipients at 1 year and 5 of 8 recipients between 1.6 and 4.5 years from transplantation. Liver transplantation from an anti-HBc-positive donor was associated with decreased 4-year survival (adjusted mortality hazard ratio of 2.4; 95% confidence interval, 1.4-4.0). CONCLUSIONS: De novo posttransplantation hepatitis B infection occurs at a high rate in recipients of donors with anti-HBc. Transmission of hepatitis B through transplantation suggests that the virus may persist in the liver despite serological resolution of infection.
Assuntos
Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Hepatite B/transmissão , Transplante de Fígado/efeitos adversos , Doadores de Tecidos , Antígenos de Superfície da Hepatite B/imunologia , HumanosRESUMO
BACKGROUND: Waiting time to liver transplantation (LTx) has dramatically lengthened, but the proportion of candidates who die awaiting transplantation has not increased. We evaluated whether longer waiting time for LTx candidates increases mortality. METHODS: A cohort of candidates listed for LTx between 1990 and 1993 by three large transplantation programs was followed for 2 years. The exposure measure was ABO blood type, which is not inherently related to outcome, but is a major determinant of waiting time. The main outcome measure was 2-year mortality, as evaluated by logistic regression analysis that controlled for differences in clinical status at the time of evaluation for LTx. RESULTS: The 308 candidates with type O blood waited longer for LTx (median 109 days) than the 399 candidates with other blood types (median 58 days) (P=0.001). Candidates listed for LTx with type O blood had better clinical status at evaluation, but then had higher pretransplantation mortality (13.3%) than other candidates (7.0%) (P=0.005). Blood group O candidates had higher 2-year mortality (26.6%) than other candidates (22.1%), which on multivariate analysis resulted in a mortality odds ratio at 2 years of 1.52 (95% confidence interval=1.04-2.23). With the difference in median waiting time between blood groups increasing from 44 days in the first year to 108 days in the third year, the 2-year mortality odds ratio also rose from 0.94 to 1.97. CONCLUSIONS: When compared with LTx candidates with other blood types, blood type O candidates have longer waiting times and higher pretransplantation mortality, which results in higher 2-year mortality.
Assuntos
Transplante de Fígado/efeitos adversos , Listas de Espera , Sistema ABO de Grupos Sanguíneos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Prospectivos , Fatores de Tempo , Doadores de Tecidos , Resultado do TratamentoRESUMO
We examined the effect of ethanol administration on intravesicular pH in intact hepatocytes by applying a flow cytometric technique to detect fluorescein-isothiocyanate-dextran (FITC-dextran) in acidic vesicles. Rats were pair-fed liquid diets containing either ethanol or isocaloric carbohydrate for 1 to 5 weeks. Our study showed that ethanol administration increased the in situ pH of hepatic lysosomes by 0.15 to 0.2 pH units. This pH increase was sufficient to cause a significant reduction in lysosomal protein degradation. Long-term ethanol administration also caused a significant alkalinization of hepatic endosomes, and this increased pH was sustained over the course of vesicular acidification in hepatocytes incubated in vitro. Direct exposure of hepatocytes from rats fed control diet to either 25 mmol/L ethanol or 50 micromol/L colchicine also brought about a rapid alkalinization of acidic vesicles in a manner that resembled that seen in hepatocytes from ethanol-fed rats. These same treatments augmented the vesicular alkalinization already present in cells from ethanol-fed animals. Although ethanol administration had no effect on the content of the hepatic mannose-6-phosphate/IGFII receptor, the results indicate that sustained alkalinization of endosomes could have important functional consequences by impairing M-6-P/IGFII receptor recycling, thereby disrupting the delivery of newly synthesized hydrolases to lysosomes. This decreased complement of hydrolases within lysosomes together with alkalinization of the intralysosomal compartment would result in an overall decrease in lysosomal proteolysis.
Assuntos
Etanol/toxicidade , Fígado/efeitos dos fármacos , Animais , Citometria de Fluxo , Concentração de Íons de Hidrogênio , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Receptor IGF Tipo 2/análiseRESUMO
BACKGROUND: The transjugular intrahepatic portosystemic shunt (TIPS) is an important treatment for complications of portal hypertension. As some authors have suggested that TIPS may facilitate liver transplantation technically, the objective of this study was to determine the impact of TIPS on the liver transplant operation and its outcome. METHODS: The analysis was designed as a retrospective cohort study using a multicenter database. Fifty-five patients with TIPS were matched with 55 controls on the basis of 10 pretransplant laboratory, clinical, and demographic features. TIPS patients and control patients were compared with regard to duration of surgery, intraoperative blood product usage, liver and renal function, volume of ascites, survival, and hospital stay. For confirmatory purposes, a parallel analysis using linear regression methods was performed. RESULTS: By matched analysis, TIPS patients had less ascites at surgery (mean 0.9+/-0.20 vs. 2.2+/-0.37 L, P=0.005) and a slightly shorter time from incision to cross-clamp (mean 2.1+/-0.10 vs. 2.5+/-0.15 hr, P=0.03). However, there were not significant differences for total operative time (mean 6.0+/-0.17 vs. 6.3+/-0.25 hr, P=1.00), blood product usage, or any other outcome variable. Regression analysis confirmed these results. CONCLUSIONS: TIPS does not significantly impact the course of liver transplantation surgery. Therefore, preoperative portal decompression solely to facilitate liver transplantation is not an appropriate indication for TIPS.
Assuntos
Transplante de Fígado/fisiologia , Derivação Portossistêmica Transjugular Intra-Hepática/normas , Estudos de Coortes , Estudos de Avaliação como Assunto , Hematócrito , Humanos , Testes de Função Renal , Testes de Função Hepática , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
Quality of life is an important factor to consider when assessing the value of liver transplantation. Using a large, prospective database of liver transplantation recipients from three clinical centers in the United States, we examined the quality of life of 346 adults before and 1 year after surgery. Five quality of life domains were evaluated (measures of disease, psychological distress and well-being, personal function, social/role function, and general health perception) with standardized questionnaires completed according to established protocol. The largest numbers of patients were distressed by fatigue and muscle weakness, both before transplantation and 1 year after surgery. Compared to baseline, recipients at follow-up noted fewer disease-related symptoms (P < .001) and lower levels of distress overall (P < .001). However, levels of distress due to excess appetite (P < .001), headaches (P = .02), and poor/blurred vision (P = .05) were more likely to increase than decrease. Although 57% to 64% of the recipients were distressed by each of the psychological conditions examined at follow-up, distress was more likely to decrease than increase (P < .001), and well-being was comparable to the general population. All measures of personal functioning improved significantly (P < .05). Fifty-eight percent of the patients prevented by their disease from going to work or school before transplantation were no longer so limited at follow-up. With the exception of marriage (P = .23), all facets of social/role functioning improved more often than worsened (P < .01). Perception of health improved remarkably, with 13.4 times as many recipients reporting improved health as reporting worse health (P < .001). We conclude that liver transplantation markedly improves the quality of life of patients with end-stage liver disease.
Assuntos
Transplante de Fígado/psicologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Fadiga/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Cefaleia/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/psicologia , Estudos Prospectivos , Ajustamento Social , Inquéritos e Questionários , Transtornos da Visão/psicologiaRESUMO
OBJECTIVE: To learn more about current attitudes and expectations of recent (June 1995) graduates of gastroenterology fellowship programs, why they chose either a private practice or academic career, and what impact managed care or health care reform had in their decision. METHODS: Between April and June 1995, and 8-page, 35-question survey questionnaire was mailed to graduating fellows and returned for evaluation. RESULTS: Graduates believed managed care had an impact on job availability, but it was not a factor in their job choice. Forty percent of the respondents reported that finding a job was either difficult or very difficult. The majority of respondents (67%) are pursuing a career in private practice. Most private practice physicians (PP) trained in 2-yr programs whereas academic physicians (AC) trained for the most part in 3-yr programs. The principal criteria on which decisions regarding job selection were based were similar between the two groups: co-workers, geographic location, access to patient care, and ability to perform endoscopy. Respondents in PP and AC expected to work 50-70 h/wk, care for patients with similar diseases, and have ample time for family. They would choose GI again as a career and believed that there is a future in GI. Salary expectations varied markedly between the two groups, and AC physicians were more concerned about their future financial needs. Twenty percent of PP physicians and 71% of AC physicians plan to participate in clinical research. CONCLUSIONS: Recent graduates of gastroenterology fellowship programs continue to have high expectations of their future careers. Although some had difficulty finding a job and stated that, although managed care had an impact on the job market, it had not yet become a major factor in their job selection.
Assuntos
Atitude do Pessoal de Saúde , Bolsas de Estudo , Gastroenterologia/educação , Adulto , Escolha da Profissão , Docentes de Medicina , Feminino , Humanos , Masculino , Programas de Assistência Gerenciada , Prática Privada , Pesquisa , Salários e Benefícios , Inquéritos e Questionários , Estados UnidosRESUMO
Septic complications have been major problems in the management of patients with obstructive jaundice and neonatal jaundice. This study investigates effects bilirubin on human T lymphocyte responses against allogeneic mixed lymphocyte reaction. In vitro exposure of human peripheral blood mononuclear cells (PBMNC) with unconjugated bilirubin at pathological levels (6 to 12 mg/dl) did not alter the subsets of CD3, CD4, CD8, CD14, CD19 and CD56 positive populations, or expression of costimulatory surface molecules CD2, CD3, CD4 and CD8. Further incubation of bilirubin-treated PBMNC with irradiated B lymphoid Raji cells after removal of the extracellular bilirubin resulted in a dose-dependent decrease of cytotoxic T lymphocyte (CTL) activity, DNA synthesis, and expression of Tac antigen (CD25) and transferrin receptor (CD71). However, no significant change of interleukin-2 (IL-2) production was observed after this incubation between bilirubin-treated and -untreated PBMNC. These results suggest that bilirubin inhibits the induction of CTL activity, and this defect may result from the impaired responsiveness against IL-2. These observations may help explain the increased infection observed in hyperbilirubinemic patients.