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Biomedical subjects

O Farges

Publications and source records attributed to O Farges.

At least 73 records · Page 4Linked to original sources

Spontaneous acceptance of rat liver allografts is associated with an early downregulation of intragraft interleukin-4 messenger RNA expression.

Liver allografts are not rejected in the fully incompatible Lewis-RT1(1) (LEW) to blood group D Agouti-RT1a (DA) rat strain combination despite an early infiltration by recipient mononucleated cells that initially display a phenotype, an ability to respond to interleukin-2 (IL-2) and donor-specific cytotoxicity indistinguishable from that observed in the rejected, DA to LEW combination. To further analyze the mechanism of this tolerance, we have compared in these two combinations, as well as in syngeneic grafts and in normal livers, the presence of intrahepatic cytokine transcripts (IL-1 alpha, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor [TNF]-alpha, TNF-beta, and transforming growth factor [TGF]-beta) by a semiquantitative polymerase chain reaction (PCR) or by northern-blotting. In normal livers or syngeneic grafts, IL-1 alpha, TNF-beta, and TGF-beta were the only cytokines detected by these methods. The levels of all cytokine transcripts were increased in allogeneic grafts. Expression of cytokine transcripts was very similar in the two allogeneic strain combinations except IL-4, which was expressed at a much lower level in the nonrejected strain than in the rejected strain from day 2 onward. We conclude that selective downregulation of IL-4 gene expression is associated with, and a potential mediator of, the induction of tolerance in this model.

Acute-Phase Reaction↗

A randomized trial of OKT3-based versus cyclosporine-based immunoprophylaxis after liver transplantation. Long-term results of a European and Australian multicenter study.

A multicenter randomized trial was performed to compare two immunosuppressive protocols after first ABO-compatible liver transplantation. Forty six patients were randomized to a 14-day treatment with Orthoclone (OKT3) in association with steroids and azathioprine, cyclosporine being progressively introduced on day 11 posttransplant. Fifty patients were randomized to a standard protocol of cyclosporine with steroids and azathioprine. Minimum follow-up was 1 year and graft and patient survivals were updated for the purpose of the study. The cumulative 1-year incidence of acute rejection tended to be greater in the cyclosporine group (75%) than in the OKT3 group (67%), especially when patients who did not receive full-course treatment with OKT3 were excluded (59%). Renal function was better preserved during the first two postoperative weeks in the OKT3 group than in the control group but plasma creatinine levels were comparable in both groups thereafter. The incidence of severe infections was lower in the OKT3 group (13.6%) than in the cyclosporine group (32%). The 4-year incidences of patient and graft survival in the OKT3 group (69% and 61%, respectively) were not different from those in the cyclosporine group (62% versus 54%, respectively). Thus this prospective trial shows that OKT3 immunoprophylaxis is a safe alternative to cyclosporine immunoprophylaxis in unselected recipients of a first liver graft.

Adolescent↗

Spontaneous acceptance of liver allografts in the rat. Analysis of the immune response.

In a model of arterialized rat liver transplantation, the biological indicators of liver dysfunction and the phenotype and in vitro function of graft-infiltrating cells have been compared in rejected (DA-to-Lew) and spontaneously accepted (Lew-to-DA) grafts, 2-8 days after grafting. Recipients of rejected and nonrejected allografts had, during this time, similar loss in body weight and plasma levels of transaminase. The markers of cholestasis, however, increased from days 3 and 4 onward in the recipients of rejected grafts, but remained low and similar in the recipients of nonrejected allografts and those of syngeneic grafts. From days 2 to 6 the phenotype, IL-2 responsiveness, and donor-specific cytotoxic potential of the leukocytes infiltrating rejected and nonrejected allografts were comparable. On days 7 and 8, although the proportion of T cell subpopulations was identical in both combinations, activated CD4+ graft-infiltrating cells were reduced in the nonrejected grafts. Also at this time, donor-specific cytotoxic cells were no longer detected in nonrejected grafts, whereas activity had reached a peak in the rejected grafts. These results suggest that liver grafts in both the LEW-->DA (grafts not rejected) and DA-->LEW (grafts rejected) strain combinations undergo tissue damage, but that the type of damage differs between the two combinations. Specifically, cholestasis was only observed in grafts that would subsequently be rejected. The difference in graft damage occurred at a very early time point (3 or 4 days after grafting), at which time neither the intensity nor phenotype of the graft infiltrate, its IL-2 responsiveness, or its cytotoxic potential varied between the two combinations. Thus, a lack of immune reactivity, as assessed by these parameters, does appear not to be responsible for spontaneous acceptance of liver transplants in the LEW-->DA strain combination.

Animals↗

The Paul Brousse liver transplant series 1989 to 1992: new trends in the last four years.

In the last four years, 551 liver transplantations have been performed at the Paul Brousse center, for a total of 840 liver transplantations performed from 1984 to 1992. Several changes have been observed in the field of liver transplantation in the past years. The field of immunosuppression was marked mainly by the advent of FK506 as a preventive treatment of rejection and as a treatment of cortico-resistant rejection. Results are still under analysis. From the surgical viewpoint, the main modification was the advent of UW solution, which extends cold ischemic time. However, our policy was to maintain the cold ischemic time at less than 12 hours. Primary indications for liver transplantations have changed with an increase in the rate of patients transplanted for cirrhosis related to hepatitis virus infection: from 24% in the period 1984-1988 to 42% in the period 1989-1992. The difference was due mainly to HCV-related cirrhosis, which increased from 8% to 20%. Alcoholic cirrhosis was a rare indication in the period 1989-1992 (3.4%); however, it was an increasing indication in the last 2 years. In order to improve the long-term results, major attention was given to the recurrence of initial liver disease. In patients transplanted for HBsAg-positive liver disease, long-term passive anti-HBs immunoprophylaxis was administered, which reduced the rate of HBV recurrence in patients without HBV replication before transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Academic Medical Centers↗

Gastroduodenal ulcer perforation in the patient with cirrhosis.

This retrospective study was done to stress the particular features of perforation of the gastroduodenal ulcer in patients with cirrhosis. From 1979 to 1987, 135 patients were operated upon for perforation of the gastroduodenal ulcer: clinical, biologic and roentgenographic data of 22 patients with cirrhosis were compared with 112 patients without cirrhosis. In the 22 patients with cirrhosis, three gastrectomies and 19 simple closures with omental patch were performed. Clinical ascites was present in 16 of 22 patients with cirrhosis. Acute abdominal pain and leukocytosis were less frequent in patients with cirrhosis (p less than 0.05), whereas associated bleeding in the upper part of the gastrointestinal (GI) tract was more frequent (p less than 0.05). In patients with cirrhosis, abnormal plasma creatinine level and associated upper GI bleeding were more frequent in patients with ascites (p less than 0.05); on the other hand, acute abdominal pain and rebound tenderness were less frequent (p less than 0.05). The incidence of pneumoperitoneum was higher in patients with cirrhosis. Surgical treatment was significantly delayed in patients with cirrhosis and ascites. Ulcers were larger in patients with cirrhosis and ascites than without (p less than 0.001). Over-all morbidity and mortality rates in patients with cirrhosis were 77.3 and 50.0 per cent, respectively. Mortality and morbidity were significantly higher in patients with ascites than without (62.5 versus 16.6 and 100 versus zero per cent, respectively), in patients with prothrombin times of less than 50 per cent and with plasma creatinine levels more than 110 micromolars.

Adult↗

Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis.

To determine whether a careful evaluation of tumor extension by preoperative computed tomography scan after intra-arterial injection of ultrafluid lipiodol and by intraoperative ultrasound examination reduced the recurrence rate of hepatocellular carcinoma after resection, a series of 47 cirrhotic patients with a single tumor operated on from 1984 was studied. Alphafetoprotein level was less than 100 ng/mL in 26 patients (55%), size of the tumor was less than 5 cm in 28 patients (59%), and capsule was present in 30 patients (63%). The resection was performed with free margin measuring 1 cm or more. The overall cumulative survival rates at 3 and 5 years were 35% and 17%, respectively. Intrahepatic recurrence was observed in 28 patients (60%), located less than 2 cm from the resection margin in only four patients. The cumulative intrahepatic recurrence rate at 3 years was 81% and was significantly higher in patients with tumor greater than or equal to 5 cm and in patients with preoperative alphafetoprotein level of greater than or equal to 100 ng/mL. In this series the cumulative intrahepatic recurrence rate at 5 years was 100%. This high recurrence rate after resection, even with careful evaluation of tumor extension, indicates that liver transplantation might be envisaged for the treatment of cirrhotic patients with resectable hepatocellular carcinoma.

Adult↗