Hypercholesterolemia in long-term survivors of liver transplantation: a comparison between cyclosporine and FK 506.
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Biomedical subjects
Publications and source records attributed to V Vargas.
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To determine whether cytomegalovirus (CMV) disease is an independent risk factor for graft loss and death after orthotopic liver transplantation, we performed a 3-year follow-up study of 143 consecutive liver transplant recipients and six patients who underwent retransplantation. Thirty-seven patients (25%) had had CMV disease and were alive after treatment. Fifty-two deaths and eight graft losses occurred. The cumulative incidence of graft failure at 1 and 3 years of follow-up were 40% and 63%, respectively, for patients with CMV disease, compared with 22% and 33%, respectively, for those without CMV disease (P < .05, logrank test). Cumulative probabilities of survival for patients with and without CMV disease were 64% and 82%, respectively, at 1 year and 46% and 69%, respectively, after 3 years (P < .05, logrank test). Multivariate analysis with use of a time-dependent Cox model showed that previous CMV disease was an independent risk factor for graft loss at 1 and 3 years of follow-up (P = .04 and P = .007) and for patient survival (P = .04 and P = .01). Our results indicate that CMV disease is a significant independent risk factor for graft loss and patient survival after liver transplantation.
OBJECTIVE: The purpose of this retrospective survey was to determine the prevalence and outcome of hepatitis C virus (HCV) infection in cirrhotic patients undergoing liver transplantation (OLT) in Spain in 1992. METHODS: Post-OLT HCV infection was defined by anti-HCV (second-generation ELISA) and/or PCR. Patients were divided into groups A (HCV-positive pre-OLT: n = 124, 46%) and B (HCV-negative pre-OLT: n = 145, 54%). RESULTS: HCV infection was more prevalent in patients originally diagnosed as having non-A non-B cirrhosis (97%) and cryptogenic cirrhosis (79%) than in patients with cholestatic or metabolic diseases. Group A patients were older (53.3+/-7.9 versus 47.6+/-9.7; P< 0.05) and had a higher prevalence of hepatocellular carcinoma (22% versus 4%, P< 0.05). Post-OLT HCV infection was 99% in group A versus 4% in group B (P< 0.05). Histological hepatitis developed in 39% (66% in group A versus 14% in group B, P< 0.05) with similar follow-up. Chronic rejection occurred in 6% (3% in group A versus 8.5% in group B, P= 0.07). Retransplantation rate (overall 8%) and two-year patient survival did not differ between groups (79% versus 72%). Graft survival was higher in group A (74% versus 65% at 2 years, P= 0.04). CONCLUSIONS: HCV-cirrhosis represented the most frequent indication for OLT in Spain in 1992. While HCV recurrence was universal, de novo acquisition was rare. HCV accounted for most post-OLT hepatitis (87%), but was not associated with chronic rejection, nor with a higher retransplantation rate. Patient survival was not different in HCV patients compared to a control group after a follow-up of 2-3 years. Therefore, at present, HCV-cirrhosis is an acceptable indication for OLT.
We report a case of Listeria monocytogenes bacteriemia with liver involvement mimicking acute viral hepatitis in a liver transplant recipient. The patient presented with fever, jaundice and alanine aminotransferase levels ten times the upper limit of normal. Liver biopsy showed signs of acute hepatitis and occasional granulomas. Both blood and liver biopsy cultures were positive for Listeria monocytogenes. The patient received a 3 week course of ampicillin and gentamicin with clinical and biochemical recovery. Liver involvement during Listeria infections is unusual, and most cases occur in patients with underlying hepatic disease and impaired cell-mediated immunity. To our knowledge only one such case has previously been reported in a liver transplant patient. Furthermore, in the present case we isolated the causal agent from the liver biopsy specimen.
OBJECTIVE: This was a study of posttraumatic stress symptoms in children and adolescents during siege conditions in Sarajevo. METHOD: Seven hundred ninety-one students aged 7-15 years were surveyed to assess symptoms of posttraumatic stress and level of deprivation. RESULTS: Girls reported more stress than boys. Loss of family members and deprivation of basic needs were associated with more symptoms. CONCLUSIONS: Personal experiences of siege are related to increased stress.
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Our objective in this study was to determine the efficacy of 2 grams a day of oral acyclovir administered for 16 weeks after transplantation for the prevention of cytomegalovirus (CMV) infection and disease in CMV-seropositive liver transplant recipients. Seventy-three adult liver transplant recipients, seropositive for CMV, were randomized to receive either 2 grams a day of oral acyclovir for 16 weeks after transplantation or no prophylaxis. The incidence of CMV disease was significantly lower in the acyclovir group (5%) than in the control group (27%; P < 0.05). By log-rank analysis, the differences in the probability of presenting CMV disease over the first 16 weeks and over the 1st year were also significant (P < 0.05). We conclude that 2 grams a day of oral acyclovir provides effective prophylaxis against CMV disease in CMV-seropositive liver transplant recipients.
We have analyzed the population of hepatitis C virus (HCV) sequences in paired liver and serum samples from four patients with chronic hepatitis C. Sequences from three different biopsy specimens from a liver explant from one patient were compared with each other and with the circulating sequences. Our results demonstrate that the circulating quasispecies does not necessarily reflect the viral population replicating in the liver and that this is not due to a macroscopic anatomic compartmentalization of HCV replication. This finding has important implications for the pathogenesis and natural history of chronic HCV infection.
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The environmentally sensitive fluorescent probes 6-propionyl-2-(N,N-dimethylamino)naphthalene (PRODAN) and 2'-(N,N-dimethylamino)-6-naphthoyl-4-trans-cyclohexanioc acid (DANCA) form complexes with the heme binding site of apohorseradish peroxidase. The dissociation constants of the PRODAN and DANCA complexes were determined from anisotropy titration data to be approximately 8.7 x 10(-5) and 3.3 x 10(-4) M, respectively. From comparison of the steady state fluorescence spectra of PRODAN and DANCA in solvents of varying dielectric constants, and in the apohorseradish peroxidase complex, we conclude that the heme binding site of horseradish peroxidase is relatively polar. The lifetimes of PRODAN and DANCA in organic solvents of varying polarities can be fit to single exponential decays. However, the lifetimes of PRODAN and DANCA associated with apohorseradish peroxidase, determined using a background subtraction method to correct for the non-negligible fluorescence of unbound probe, fit best to a distribution of lifetime values. We attribute these lifetime distributions to microenvironmental heterogeneity which is also consistent with the observed dependence of the emission maxima of PRODAN-apohorseradish peroxidase upon the excitation wavelength. In neither the PRODAN nor the DANCA case was evidence found in the time-resolved data for relaxation of the protein matrix around the excited state probe dipole.
Between 1987 and 1993, 53 hepatic resections for hepatocellular carcinoma (HCC) were performed in 51 patients with cirrhosis. Limited hepatic resection was performed in 66 per cent of patients. The postoperative mortality rate was 13 per cent. The tumours recurred in 27 patients (53 per cent), and the cumulative recurrence rate at 1 and 4 years was 41 and 89 per cent, respectively. Mean time to recurrence was 11.7 months and the most frequent site was the liver (21 patients). The only significant risk factor for recurrence was symptomatic tumours. The recurrence rate of HCC in patients with cirrhosis with surgical resection alone is high and actuarial survival at 4 years is very low. Other approaches to the treatment of HCC in patients with cirrhosis require consideration.
Several risk factors have been reported that may favour the development of chronic rejection. From October 1988 to December 1993, 97 liver transplants with survival of more than 3 months were included in the study. Fifty-two patients (54.1%) had chronic hepatitis C virus (HCV) infection before liver transplantation. Immunosuppression consisted of cyclosporine A and prednisone, whereas 14 patients received FK 506 and prednisone. Severe graft HCV reinfection was present in 32 patients (61.5%) after liver transplantation and chronic graft hepatitis C was found in 26 cases at the end of the study. Chronic rejection occurred in 8 of 97 allografts (8.25%); 5 presented chronic rejection and concomitant chronic graft hepatitis C. The incidence of chronic rejection in patients with HCV infection before liver transplantation (9.6%) did not differ when compared with the negative HCV patients (6.6%). However, when the 26 cases that developed graft dysfunction due to chronic hepatitis C after liver transplantation were considered, 5 presented chronic rejection, a significantly higher incidence than in the remaining patients (3 of 71) (Yates chi-square test: P < 0.05). In our experience, there appears to be a relationship between the development of chronic rejection and chronic hepatitis C in the graft after liver transplantation.
BACKGROUND & AIMS: Paracentesis associated with plasma expanders is widely used for the treatment of ascites in cirrhosis. This study investigated the clinical importance of paracentesis-induced-circulatory dysfunction and compared the efficacy of albumin, dextran 70, and polygeline in preventing this complication. METHODS: A total of 289 cirrhotic patients with ascites were randomized to treatment by total paracentesis plus intravenous albumin (97 patients), dextran 70 (93 patients), or polygeline (99 patients). Postparacentesis circulatory dysfunction was defined as an increase in plasma renin activity on the sixth day after paracentesis of more than 50% of the pretreatment value to a level > 4 ng.mL-1.h-1. RESULTS: Postparacentesis circulatory dysfunction occurred more frequently in patients treated with dextran 70 (34.4%; P = 0.018) or polygeline (37.8%; P = 0.004) than in those receiving albumin (18.5%). The plasma expander used and the volume of ascites removed were independent predictors of this complication. Postparacentesis circulatory dysfunction persisted during follow-up and was associated with a shorter time to first readmission (1.3 +/- 0.5 vs. 3.5 +/- 0.8 months, median +/- SEM; P = 0.03) and shorter survival (9.3 +/- 4.2 vs. 16.9 +/- 4.3 months; P = 0.01). Creatinine and sodium levels in serum, and Child-Pugh score at inclusion, and postparacentesis circulatory dysfunction were independent predictors of survival. CONCLUSIONS: Postparacentesis circulatory dysfunction is not spontaneously reversible and is associated with a shorter time to first readmission and shorter survival. Albumin is the best plasma expander to prevent this complication.
BACKGROUND & AIMS: Treatment of spontaneous bacterial peritonitis currently involves intravenous antibiotic administration. To test the possibility of treating spontaneous bacterial peritonitis with oral antibiotics, oral ofloxacin was compared with intravenous cefotaxime in this infection. METHODS: One hundred twenty-three cirrhotics with uncomplicated spontaneous bacterial peritonitis (no septic shock, grade II-IV hepatic encephalopathy, serum creatinine level of > 3 mg/dL, and gastrointestinal hemorrhage or ileus) were randomly given oral ofloxacin (64 patients) or intravenous cefotaxime (59 patients). RESULTS: Infection resolution rate was 84% in the ofloxacin group and 85% in the cefotaxime group. Peak serum levels and trough serum and ascitic fluid levels of ofloxacin and cefotaxime measured on days 3 (23 patients) and 6 (11 patients) of therapy were greater than the minimal inhibitory concentration of isolated organisms. Hospital survival rate was 81% in each group of patients. Blood urea nitrogen and hepatic encephalopathy at diagnosis were associated with prognosis. None of the 36 nonazotemic patients with community-acquired spontaneous bacterial peritonitis and without hepatic encephalopathy developed complications during hospitalization, and all were alive at time of discharge. CONCLUSIONS: Oral ofloxacin is as effective as intravenous cefotaxime in uncomplicated spontaneous bacterial peritonitis. Nonazotemic cirrhotic patients with uncomplicated community-acquired spontaneous bacterial peritonitis and without hepatic encephalopathy have an excellent prognosis and may be treated with oral ofloxacin without requiring hospitalization.
BACKGROUND/AIMS: The role of crossmatching in liver transplantation is controversial. The aim of this study was to investigate retrospectively the effect of sensitization and IgG lymphocytotoxic crossmatching on liver transplantation. METHODS/RESULTS: Over 5 years, 20 of 243 (8.2%) first liver transplants were performed with a positive crossmatch and their outcome was compared with the remaining 223 performed with a negative crossmatch. Women had a higher incidence of positive crossmatch than men (p < 0.001). Significant differences in mean panel reactive antibody of 2.7% and 43.3% were found in negative and positive crossmatch patients, respectively (p < 0.001). Severe early rejection resulting in graft loss occurred in eight of 20 positive crossmatch patients, and only one of 223 negative crossmatch patients (p < 0.001). Five of the remaining positive crossmatch patients suffered several acute rejection episodes some months after liver transplantation. Two of 20 in the positive crossmatch group developed chronic rejection (10%) compared with ten of 223 negatives (4.4%) (N.S). Nine of 16 positive crossmatch female recipients suffered graft loss and seven died, representing 1-year graft and patient survival of 56% and 43%, respectively. Fifteen of 68 negative crossmatch female recipients presented graft loss and 12 died, accounting for 1-year patient and graft survival of 82% and 78% (p < 0.005), respectively. Five patients (20%) displayed positive crossmatch at the time of retransplantation, compared with 24 (10%) who were negative (N.S). CONCLUSION: Our experience confirms the adverse impact of a positive crossmatch in liver transplantation, particularly in female recipients. Candidates with high panel reactive antibody are more likely to display a positive crossmatch, and therefore to develop early severe rejection and graft failure.
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Since Rubner established in 1883 the "surface law", the basal metabolic rate (kcal/24 h) is expressed per square meter of body surface. This so-called biological law has been extrapolated to the standardization of several other functions as, for instance, to variables of the cardiovascular, respiratory and renal systems, which may lead to erroneous conclusions. The present paper is an attempt to establish, by means of the dimensional analysis and one of the theories of biological similarity, an allometric indexation procedure, which yields mass-independent numbers (MIN) for all functions which can be defined by means of the MLT-system of physics (M = mass; L = length; and T = time).