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Biomedical subjects

R Adam

Publications and source records attributed to R Adam.

At least 19 recordsLinked to original sources
PubMed1992

Effect of extended cold ischaemia with UW solution on graft function after liver transplantation.

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.

Adenosine↗
PubMed1992

Lipid and apolipoprotein changes after orthotopic liver transplantation for end-stage liver diseases.

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.

Adult↗
PubMed1992

A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer.

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.

Adult↗
PubMed1992

Experimental study of the protective effect of intermittent hepatic pedicle clamping in the rat.

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.

Animals↗
PubMed1992

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↗
PubMed1992

Partial portacaval shunt: renaissance of an old concept.

BACKGROUND: Partial diversion of the portal system aims to reduce portal pressure sufficiently to prevent variceal hemorrhage but still maintain adequate hepatic portal flow. METHODS: Partial portacaval shunts were performed in 25 patients with cirrhosis with portal hypertension and esophageal varices, either as a primary procedure (n = 16) or for failure of endoscopic sclerotherapy (n = 9), with ringed polytetrafluoroethylene prostheses (8, 10, or 12 mm). RESULTS: All patients have now been followed up for at least 1 year. The operative mortality rate (2 months) was 4%. In 24 patients who survived beyond the initial perioperative period, there was no recurrence of variceal bleeding. Cumulative shunt patency (up to 4 years) is 96%. Acute encephalopathy was detected in two patients (8%), but no patients had signs of chronic encephalopathy. Intraoperative pressure measurements revealed a significant correlation between decreasing diameter of the graft and the percentage reduction of the portacaval pressure gradient. Selective angiography, performed 1 year after surgery, revealed that hepatopetal flow was maintained in 70% of patients with a 10 mm shunt. CONCLUSIONS: It is possible to achieve a partial portacaval shunt, related to the diameter of the prosthesis, that preserves hepatopetal flow in the majority of patients and is associated with a very low incidence of shunt thrombosis. This effectively prevents recurrent variceal bleeding and significant postoperative encephalopathy. The performance of subsequent orthotopic liver transplantation is not compromised. The technique is recommended, either as a primary procedure or when sclerotherapy has failed, in patients with good liver function who are unlikely to require early liver transplantation (grade A and some grade B cirrhosis).

Adolescent↗
PubMed1990

Phase I trial of 5-day continuous venous infusion of oxaliplatin at circadian rhythm-modulated rate compared with constant rate.

The toxic effects and tissue uptake of both cisplatin and oxaliplatin--[(1R, 2R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)-O,O']platinum--were previously shown to vary similarly according to dosing time in mice. A 4-hour infusion of cisplatin resulted in fewer side effects and allowed administration of higher doses at 16 hours than at 4 hours in patients with cancer. We hypothesized that the continuous venous infusion of oxaliplatin for 5 days would be less toxic and would deliver a higher dose to the patient if the drug were infused at a circadian rhythm-modulated rate (peak at 16 hr; schedule B) rather than at a constant rate (schedule A). We tested this hypothesis in a randomized phase I trial. We escalated the dose of oxaliplatin to the patient by 25 mg/m2 per course. Courses were repeated every 3 weeks. An external, multichannel, programmable-in-time pump was used for the infusions. Toxicity was assessable for 94 courses in 23 patients (12 patients with breast carcinoma, nine with hepatocellular carcinoma, and two with cholangiocarcinoma). The incidence of neutropenia of World Health Organization grades II-IV and the incidence of distal paresthesias were 10 or more times higher (P less than .05) with schedule A than with schedule B. In addition, vomiting was 55% higher (P = .15) with schedule A than with schedule B. Furthermore, with schedule B, the mean dose of oxaliplatin (P less than .001) and its maximum tolerated dose (P = .06) could be increased by 15% over those doses with schedule A. An objective response was achieved in two of the 12 patients with previously treated breast cancer. We recommend that the dose of oxaliplatin for phase II trials be 175 mg/m2, delivered according to the circadian rhythm-modulated rate.

Adult↗
PubMed1990

Options for elective treatment of portal hypertension in cirrhotic patients in the transplantation era.

We review herein our experience in the management of bleeding esophageal varices in cirrhotic patients and consider our findings in light of the dramatic changes in the treatment of cirrhosis resulting from the more widespread use of orthotopic liver transplantation (OLT). It does not seem realistic, at present, to propose OLT as the only effective treatment of variceal bleeding for a variety of reasons, and there remains a large group of patients who are noncompliant or unsuitable for liver transplantation. We propose that initial bleeding be controlled by endoscopic sclerotherapy, thereby allowing careful evaluation to be made electively. Grade A patients appear to be managed best by a reduced-size portacaval shunt (RPS) with prospects of good survival and few complications. Grade B patients can be managed by either sclerotherapy, RPS, or OLT, depending upon individual circumstances. Grade C patients are best managed by liver transplantation, again with excellent survival. In those grade C patients not deemed suitable for OLT (especially alcoholic patients), long-term endoscopic sclerotherapy is the best option. Changes in patient status may sometimes require revision of the treatment decision.

Adolescent↗
PubMed1990

[Value of scalene lymph node biopsy in the treatment plan of advanced cervix cancer].

112 patients with carcinoma of the cervix had a scalene lymph nodes biopsy. In 22 cases (20%) metastases to the scalene lymph nodes were detected. In these cases, systemic spread of the disease beyond curative surgical or radiation therapy possibilities had to be considered. In our findings, patients with positive scalene lymph nodes had a mean survival time of 10 months after detection of the metastases in the scalene lymph nodes. Considering the systemic dissemination of the disease, patients with positive scalene lymph nodes may be treated only by palliative methods and can be spared further high-risk noncurative treatment.

Biopsy↗
PubMed1990

Orthotopic liver transplantation with hepatic artery anastomoses. Hemodynamics and response to hemorrhage in conscious rats.

Orthotopic liver isotransplantation was performed in one group of Lewis rats using cuffs for the portal vein and the infrahepatic vena cava, stents for the hepatic artery and the bile duct. Three other groups were also investigated: group A, normal rats; group B, sham-transplanted rats (clamping of the vessels, washing of the liver, placing cuffs around the portal vein); and group C, sham-transplanted rats with ligature section of the hepatic artery. Blood-flow measurements were performed, 1 week after the surgical procedure, with the radioactive microsphere method in conscious animals. Transplanted rats exhibited significant (ANOVA, P less than 0.05) increase in cardiac index and decrease in mean arterial pressure and systemic vascular resistance. Blood flows of the portal territory and to the kidneys were not significantly modified. Arterial liver blood flow and arterial liver vascular resistance in rats with liver transplantation were not significantly different between normal and sham-transplanted rats but were significantly different from rats with ligature of the hepatic artery. These results confirm the validity of the method used for vascular anastomoses. Hypotensive hemorrhage (2 ml/100 g bw) induced marked hemodynamic changes, but rats with liver transplantation when compared with normal and sham-transplanted rats exhibited the following: (a) significantly lower percentage of decrease in cardiac index and in mean arterial pressure; and (b) significantly higher renal and portal tributary blood flows. Plasma catecholamine concentrations and plasma volume were higher in rats with liver transplantation than in normal rats but were not significantly different from sham-operated rats. Histologic examination of the liver revealed slight portal edema in sham-operated rats and small necrotic areas in the liver, probably corresponding to the reperfusion injury, in rats with liver transplantation. In conclusion, the method described for the four vascular anastomoses allows functional perfusion of the transplanted liver. Rats with liver transplantation exhibited a hyperkinetic circulatory syndrome and an improved tolerance to hemorrhage. Changes in plasma catecholamine concentrations and in plasma volume did not account for the hemodynamic changes.

Anastomosis, Surgical↗