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Biomedical subjects

H Bismuth

Publications and source records attributed to H Bismuth.

At least 163 records · Page 9Linked to original sources
PubMed1995

A phase I-II trial of five-day continuous intravenous infusion of 5-fluorouracil delivered at circadian rhythm modulated rate in patients with metastatic colorectal cancer.

The toxicity of 5-fluorouracil (5-FU) was decreased by two to eight-fold if this drug was injected in mice near the middle of the day (rest span) rather than in the middle of the night (activity span). If the rhythm in 5-FU toxicity is linked to the sleep-wakefulness endogenous circadian cycle across species, the least toxic time in man would correspond to 4.00 hours at night. The availability of a single-reservoir programmable-in-time external ambulatory pump (Chronopump, Autosyringe, Hooksett, USA) allowed us to perform a first test of this hypothesis. Five-FU was infused for 5 consecutive days, via an implanted venous access port, with peak drug delivery at 4.00 hours and no infusion from 18.00 to 22.00 hours. Each course was repeated after a free interval of 16 days. Intrapatient dose escalation was planned from 4 to 9 g/m2/course (800 to 1800 mg/m2/day x 5 days) if toxicity was less than grade 2 according to the World Health Organization (W.H.O.). Thirty-five patients with metastatic colorectal cancer were treated; 15 (41%) had received previous therapy, 22 (63%) had W.H.O. performance status of 2 or greater, and 19 (54%) had two or more sites involved. Grade 2 or greater toxicity was encountered in less than 5% of the courses, indicating an adequate control of toxicity via dose adjustment. Oral mucositis, diarrhea, and/or hand-foot syndrome limited dose escalation, and their incidence was dose dependent. Median maximal tolerated dose was 7.5 mg/m2/course in 30 patients assessed for this endpoint.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

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↗
PubMed1994

[Bacterio-myco-virological surveillance of patients undergoing transplantation].

Bacterial and viral infectious complications are the main complications encountered after transplantation. Prevention of these complications should be done by a pre-transplant bacterial and virologic screening in the recipient, by a pre-transplant screening in the donor, and by routine bacterial and viral cultures after transplantation. Patients at high risk of post transplant infectious complication should be closely monitored, patients with denutrition, patients with a long stay in the ICU, patients at high risk of CMV primary-infection (donor CMV positive, recipient CMV negative), and patients receiving strong immuno-suppressive treatment for acute or chronic rejection. A better prevention and management of these infectious complications will improve the result of transplantation and reduce the post-transplant infectious morbidity.

Bacterial Infections↗
PubMed1994

The course of hepatitis C virus infection after liver transplantation.

Hepatitis C virus-induced liver disease is becoming a main indication for liver transplantation. Recurrence of hepatitis after transplantation has been reported, but its long-term consequences are unknown. Seventy-nine patients positive for hepatitis C virus (group 1) and 106 subjects negative for hepatitis C virus antibody (group 2) with a mean follow-up of 4 yr were retrospectively studied by means of serology, nested polymerase chain reaction and branched-DNA technology before and after liver transplantation. The actuarial rates of hepatitis C virus-related acute hepatitis were 72% and 20% at 4 yr in groups 1 and 2, respectively. Progression to chronic active hepatitis occurred in 61% and 36% of the subjects within 3 yr of the onset of recurrent and acquired hepatitis, respectively. No case of acute graft failure and two cases of cirrhosis were related to recurrent or acquired hepatitis C virus liver disease. Hepatitis C virus RNA levels were significantly increased in cases of hepatitis after transplantation. In contrast, the pretransplant hepatitis C virus RNA level was not predictive of recurrence. Our results establish the general persistence of hepatitis C virus infection after liver transplantation, the frequency and the severe course of recurrent liver disease. However, liver transplantation in hepatitis C virus antibody-positive patients still has a good medium-term prognosis.

Adult↗
PubMed1994

An experimental approach for dynamic rat liver observation in vivo and ex vivo by 31P localized MR spectroscopy for follow-up of liver status at different steps of orthotopic transplantation--a feasibility study.

An experimental approach was evaluated to perform a follow-up of rat liver transplantation by 31P spectroscopy. The approach is based on the use of an implanted surface coil attached to the liver and inductively coupled to the receiver/transmitter line by an external coupling loop. Spatial localization to the liver was performed by selective excitation and dephasing of spins in a slice between the implanted and the coupling coil, the slice being positioned on a proton image acquired prior to spectroscopy. Characteristics of the protocol were established on a phantom and in vivo on non-transplanted rat livers indicating good localization and high signal-to-noise ratio. Preliminary results obtained on transplanted livers revealed a relation between evolution of the 31P spectrum and animal survival. As shown in separate experiments, the same technique also enabled easy acquisition of the 31P profile of livers stored at 4 degrees C in University of Wisconsin solution. Therefore, the experimental approach described here opens up the possibility of measuring changes of the 31P profile on the same liver during the whole transplantation procedure, i.e., in the donor, during preservation and after transplantation, and comparing evolution of spectra with transplantation outcome.

Animals↗
PubMed1994

A magnetic resonance study of the effect of nutritional status on cold-preserved murine liver.

BACKGROUND/AIMS: Clinical and experimental studies suggest a link between nutritional status and the recovery of hepatic function after hypoxic and hypothermic insults. This study aimed at determining the metabolic pathways involved in such recovery as a function of nutrition. METHODS: Livers from fed and fasted mice were perfused with oxygenated Krebs'-Henseleit buffer (RBKB). After depletion of glycogen, 31P and 13C nuclear magnetic resonance spectra were acquired. Livers were flushed with University of Wisconsin solution and stored at 4 degrees C for 0, 24, or 48 hours. At reperfusion with RBKB, recovery of nucleoside triphosphates (NTP) was followed up. After 45 minutes, [3-13C]alanine was added and substrate consumption and metabolic products assessed. RESULTS: Livers from fed animals recovered more NTP at reperfusion both after 24 hours (85% +/- 11% vs. 67% +/- 7%; P < 0.01) and 48 hours (61% +/- 10% vs. 36% +/- 10%; P < 0.01, respectively) of cold storage. Gluconeogenesis as reflected by [3-13C]alanine consumption was also higher from fed animals. Hepatic glycogen before preservation was low in both groups. Livers from fasted animals contained increased triglyceride levels, but these did not contribute to NTP production at reperfusion. CONCLUSIONS: Livers from fed mice show an improved recovery after cold ischemia. Glycogen levels are low in these organs, and NTP synthesis must be from substrates other than fatty acids.

Adenosine↗