Biomedical subjects
Publications and source records attributed to R Adam.
One hundred and eleven naiads from six different dragonfly species were investigated for the presence of metacercariae. Sixty-nine animals (62.2%) were infected with intensities up to more than 150 cysts per animal. The metacercarial cysts were characterized by light and scanning electron microscopy. Two types of metacercariae could be differentiated by morphological features of cyst surface, cyst wall and size.
An original technique balloon dilatation through an ileal vein for treatment of portal vein stenosis after HT is described. In four of five patients, this minimally invasive procedure permitted avoidance of extensive dissection of the hepatic pedicle. This technique should be the treatment of choice, or at least in the first step, for portal vein stenosis after HT.
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The dramatic development of liver transplantation compared to a relative shortage of donors has brought a renewed interest to xenotransplantation. Because of anatomical and immunological compatibilities, nonhuman primates are the most appropriate donors. The aim of this work was to analyze the different problems of a baboon-to-man liver xenotransplantation. Thirty baboons bred in a French Primatology Center were studied. The analysis of anatomical, microbiological, and immunological data showed that only 8 baboons out of 30 were suitable as donors for xenotransplantation. Considering these data and the ethical issues, the actual feasibility of xenotransplantation programs is discussed.
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Studies in animals on the use of UW solution in liver transplantation have shown an inverse relation between cold ischaemia time (CIT) and graft function. There are few clinical data on this relation in human beings. We have investigated the effect of extended cold ischaemia in a prospective study. We assessed early graft function and subsequent outcome for 306 consecutive elective liver transplantations; for analyses, grafts were grouped according to CIT (< 12 h group A, > or = 12 h group B), since a preliminary study identified 12 h as a significant cut-off point. Initial graft function was better in group A than group B, as shown by maximum alanine aminotransferase activity (mean 623 [805] vs 946 [1148], p = 0.02), bile production on days 1-3 (p < 0.05), maximum serum bilirubin by day 10 (206 [166] vs 244 [163] mumol/l, p = 0.04), and frequencies of primary non-function (1 [0.4%] vs 4 [7%], p = 0.006) and hepatocyte necrosis on routine biopsy sample after reperfusion (18% vs 31%, p = 0.04). Long-term outcome was also better in group A than group B; graft and patient survival rates were higher and fewer retransplantations were needed. These findings suggest that cold ischaemia in UW solution for longer than 12 h is a risk factor for graft function and patient survival. We recommend that the limit of the safe CIT be reconsidered.
Orthotopic liver transplantation was performed in 37 patients with different endstage liver diseases. Changes in lipid and apolipoprotein concentrations were followed daily from day 1 to 20 after surgery and regularly thereafter until 12 months. When the acute effects of surgery had cleared away, there was a sharp drop in HDL-C, apo A-I and A-II from day 1 to 5, a stabilization at their lowest values from day 5 to 15 and then a progressive rise. Contrasting with this drop, triglycerides, apo B, C-II and C-III increased from day 1 to 5 with variable concentrations thereafter. Apo SAA considerably increased early after surgery and remained significantly higher than normal in most patients after 12 months. All other parameters returned to normal from 3 to 6 months after transplant. The mechanism leading to these lipid and apolipoprotein changes are discussed with respect to the distant effect of infusions, re-alimentation, immunosuppressive therapy and lipoprotein metabolism. The apolipoprotein concentrations appear very useful indicators of functional liver recovery.
A significant increase in the dose intensity of chemotherapy with fluoropyrimidines and platinum complexes has resulted from selective circadian timing and/or circadian modulation of the infusion rate. The relevance of such chronopharmacologic strategy for improving the outcome of metastatic colorectal cancer was evaluated in an extended Phase II clinical trial involving 93 patients. Of these, 49% previously had received chemotherapy and/or radiation therapy. The drugs 5-fluorouracil (5-FU, 700 mg/m2/d) and folinic acid (FA, 300 mg/m2/d) combined with oxaliplatin (l-OHP, a nonnephrotoxic platinum complex, 25 mg/m2/d) were infused continuously for 5 days every 3 weeks. In a pilot randomized study, the infusion of all three drugs at a constant rate resulted in World Health Organization (WHO) Grade 3 or 4 toxicity in all four patients compared with no such toxicity in four patients if the infusion rate was modulated according to circadian rhythms. In this Phase II trial, drug delivery was modulated sinusoidally over the 24-hour day with peak flow rates at 4 AM for 5-FU and FA and at 4 PM for l-OHP, using an ambulatory programmable-in-time pump. All patients and 784 of 839 courses (93%) were evaluable for toxicity. Dose-limiting toxicities (WHO Grade 2 to 4) included diarrhea (19% of courses) and vomiting (35% of courses). In addition, WHO Grade 2 to 4 hematologic or mucosal toxicity, respectively, occurred in 2.5% and 7% of courses. Two toxic deaths were encountered. Peripheral sensory neuropathy led to discontinuation of l-OHP in 14 patients after 7 to 12 courses; it completely disappeared within 3 months. Fifty-four of the 93 patients had an objective response (58%; 95% confidence limits, 48% to 68%), irrespective of previous treatment or prior documented progression while receiving standard chemotherapy with 5-FU and FA or continuous 5-FU. Complete responses (CR) were seen in 6 patients (4 of which were proved histologically) and, after surgery, in 12 additional patients (overall CR rate, 18 of 93 [19%]; 95% confidence limits, 11% to 27%). Median progression-free survival (PFS) and overall survival were, respectively, 10 and 15 months, irrespective of prior therapy. Both PFS and survival were significantly longer in patients with a good performance status (PS, 0 or 1, by WHO criteria; respectively, 12 and 21 months) than in patients with poor PS (respectively, 8 and 10 months; P less than 0.01, by log-rank test). This chronopharmacologic protocol may have circumvented, to some extent, both the natural and acquired resistance of colorectal cancer to chemotherapy.
The tolerance of the liver to ischaemia during intermittent clamping of the hepatic pedicle was compared with that during a continuous Pringle manoeuvre. Three groups of rats undergoing total durations of clamping of 60, 90 and 120 min were studied. A temporary peroperative portacaval shunt was used to exclude the effects of splanchnic venous stasis and allow independent study of the effects of hepatic ischaemia. In each group, three methods of portal clamping were evaluated: a continuous Pringle manoeuvre (n = 10), a 30-min intermittent clamping (n = 10) and a 15-min intermittent clamping (n = 10). The clamp release time between the periods of liver ischaemia was 5 min. Survival at day 7 and postoperative changes in liver function (transaminase enzymes, bilirubin, bromsulphthalein elimination, liver adenosine 5'-triphosphate levels) were recorded. Intermittent clamping of the pedicle was tolerated significantly better than continuous clamping. This method optimizes the ability of the liver to tolerate extended periods of ischaemia. For a given duration of ischaemia, no additional improvement could be produced by shortening the intermittent clamping period from 30 to 15 min. These data suggest that, when the Pringle manoeuvre is used, it should be applied intermittently rather than continuously.
The effect of storage temperature on early graft function following liver transplantation was investigated by analyzing the results following transplantation during three periods in which different techniques for graft storage were used. The techniques involved ice-packing (period 1), storage in a standard operating room refrigerator without ice-packing (period 2) and storage in an accurately controlled refrigerator without ice-packing (period 3). In period 2 there was a significantly higher incidence of histological lesions, primary non-function and retransplantation compared to periods 1 and 3. It was concluded that this was due to inaccurate control of the standard refrigerator in period 2, thus allowing the temperature of the graft to increase, while in periods 1 and 3 the graft temperature was kept close to 4 degrees C by ice-packing and accurate refrigerator control, respectively. These results demonstrate that accurate control of storage temperature is important in terms of subsequent graft function. This may become more important as storage times are progressively increased with the use of UW solution.
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)
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