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G den Butter

Publications and source records attributed to G den Butter.

12 recordsLinked to original sources

Comparison of solutions for preservation of the rabbit liver as tested by isolated perfusion.

The University of Wisconsin (UW) solution consists of a relatively complex mixture of agents. In this study we compared simpler preservation solutions, namely, histidine-tryptophan-ketoglutarate (HTK) and phosphate-buffered sucrose (PBS) with different compositions of UW solution in the isolated perfused rabbit liver model. Livers were stored cold for 24 and 48 h. After 24 h of preservation, the amount of bile produced in UW-preserved livers was significantly greater (P < 0.05) than that in HTK-preserved livers. Also, there was less LDH released into the perfusate in UW-preserved livers. There was more edema and lower K +/Na+rations in HTK-preserved livers than in UW-preserved livers (all data P < 0.05). After 48 h of preservation, the differences between livers preserved in UW or HTK solution were less noticeable than at 24 h and bile production was similar. LDH and AST release were greater in HTK-preserved livers than in UW livers, but these differences were not statistically significant. Preservation in PBS for 48 h was worse than in either UW or HTK solution. Substitution of polyethylene glycol (PEG) for hydroxyethyl starch (HES) in 48-h UW-preserved livers was not effective. We conclude that solutions simpler in composition than UW solution may be effective in kidney transplantation but do not appear suitable for successful liver preservation.

Adenosine↗

The tissue hydration state in UW-preserved human donor livers. A clinical study of the relation between proton magnetic resonance relaxation times, donor condition, preservation procedure, and early graft function.

To determine the relation between tissue hydration state--as indicated by tissue proton magnetic resonance relaxation times--in UW-preserved human donor livers and viability parameters of the donor and early graft function, "ex vivo" magnetic resonance relaxometry was performed with a clinical MR imaging system. Relaxometric data were obtained from MR images in which signal intensities were directly proportional to T1 and T2. Forty-three subsequently transplanted livers and five discarded livers were studied. The donor serum concentrations of direct and total bilirubin had a positive correlation with T1 (P < 0.05 and P < 0.01, respectively). Sequential measurements in 7 livers demonstrated a firm time relation between the cold storage time and the length of the relaxation times. As cold storage time lengthened, T1 and T2 shortened. T1 of the donor liver showed a significant negative correlation with recipient ASAT and ALAT values on days 1, 2, and 3 after transplantation. T1 in the discarded group was significantly higher than T1 in the accepted group. T2 was not different in the two groups. It is concluded that in UW-preserved human donor livers, the tissue hydration state, as indicated by the tissue MR relaxation times, is largely independent of the clinical condition of the organ donor and the preservation procedure. An optimum tissue hydration state, in UW-preserved donors liver might have protective properties against parenchymal damage, although the clinical consequences appear to be of minor importance. The capacity of relaxometry as a discriminative instrument to accept or to discard donor livers is poor.

Adenosine↗

Effect of glycine on isolated, perfused rabbit livers following 48-hour preservation in University of Wisconsin solution without glutathione.

Glycine has been shown to decrease membrane injury in isolated cells due to hypoxia or cold ischemia. The mechanisms of action of glycine are not known, but glycine may be useful in organ preservation solutions or in treating recipients of liver transplantation. In this study the isolated, perfused rabbit liver was used to measure how glycine affected liver performance after 48-h preservation in University of Wisconsin (UW) solution without added glutathione. UW solution is less effective for 48-h liver preservation when glutathione is omitted. Rabbit livers stored for 48 h without glutathione show a large increase in enzyme release (LDH and AST) from the liver and a reduction in bile production. The addition of 15 mM glycine to UW solution, in place of glutathione, did not improve bile production or reduce enzyme release. However, infusion of 10 mM glycine into the reperfused liver lowered LDH release significantly (from 2383 +/- 562 units/100 g to 1426 +/- 286 units/100 g) during the initial reperfusion of the 48-h preserved liver. Hepatamine, a parenteral nutrition solution containing glycine, as well as other amino acids, was also effective in lowering LDH release from the preserved liver. Although glycine reduced LDH release, it did not decrease the amount of AST released from the liver, nor did it improve bile production. Thus, we conclude that glycine, either in UW solution or given to the liver upon reperfusion, has no significantly beneficial effect as tested in this model. Further testing of glycine, however, should be conducted in an orthotopic transplant model in the rat or dog.

Adenosine↗

Effect of glycine in dog and rat liver transplantation.

Glycine has been shown to protect renal tubule cells and hepatocytes from ischemia, ATP depletion, and cold storage injury. Glycine may be a useful additive to organ preservation solutions or suppress reperfusion injury by infusion into recipients of liver transplantation. In this study, the effects of glycine on survival and postoperative liver injury were studied in the rat and dog orthotopic transplant model. Rat livers preserved for 30 hr in the University of Wisconsin (UW) solution were 50% viable (3 of 6 survivors for 7 days). When glutathione was replaced by 10 mM glycine, survival increased to 100% (6 of 6). There was a significant reduction in hepatocellular injury at the end of preservation (lactate dehydrogenase [LDH] in the pretransplant flush-out of the liver was lower in the glycine group) and after transplantation (serum LDH concentration 6 hr after transplant was lower in the glycine group). In the dog, omission of glutathione from the UW solution resulted in 33% survival (48-hr preservation model) versus 100% survival with glutathione. Replacing glutathione in the UW solution by glycine did not improve survival (33% after 48 hr of preservation). However, when glycine was given to recipients of livers preserved in the UW solution for 24 or 48 hr, there was a decrease in the degree of hepatocellular injury. After 48 hr of preservation, peak aspartate aminotransferase, alanine aminotransferase, and LDH were reduced by about 45-55% when glycine was given to the recipient. Although the differences, with and without glycine treatment of the recipients, did not reach statistical significance, there was a noticeable reduction in hepatocellular injury with glycine. There was 100% survival of dogs in the groups that received livers preserved with the UW solution plus or minus glycine infusion. Hepatamine, a parenteral nutrition solution containing glycine and other amino acids increased hepatocellular injury (higher concentrations of aspartate aminotransferase, alanine transferase, and LDH versus control 48-hr preserved livers), although all dogs survived. This study shows that glycine is cytoprotective when administered to recipients of livers preserved for 24 or 48 hr and suppresses hepatocellular injury, as reflected in a reduction in the concentration of serum enzymes. However, the differences, with and without glycine, were, at best, marginal and further studies are needed to determine whether glycine would make a significant improvement in liver preservation and prevent primary nonfunction.

Adenosine↗

Arterial fibrodysplasia: rapid progression complicated by rupture of a visceral aneurysm into the gastrointestinal tract.

We report the case of a 44-year-old woman who had extensive stenosis and dilatation of the aortoiliac arteries and an aneurysm of the superior mesenteric artery as a result of fibrodysplasia. Both the aortoiliac and the superior mesenteric arteries were treated by resection and reconstruction. Within one year after this operation, fibrodysplastic aneurysms developed in previously angiographically normal visceral arteries. The patient came to us with massive lower gastrointestinal bleeding caused by rupture of a visceral fibrodysplastic aneurysm of the middle colic artery into the transverse colon. The classification, the origin, the localization, and the natural history of fibrodysplasia are discussed.

Adult↗

Side effects and immunogenicity of murine lymphocyte-specific monoclonal antibodies in subhuman primates.

The immediate side effects of lymphocyte-specific monoclonal antibody treatment of nearly 150 monkeys is documented in this study. Immediate side effects were only seen with antibodies specific for CD3 and CD8. These side effects are most likely related to stimulation of T cells to produce lymphokines (CD3) and/or to the rapid cell clearance (CD3 and CD8). No immediate effects were observed when CD4 or major histocompatibility complex class II-specific antibodies were injected. These antibodies may therefore be considered for the treatment of graft rejection or autoimmune diseases. Of the 43 animals that received a monoclonal antibody (MoAb) at least 2 years and up to 5 years prior to this study, none has shown any late effects of MoAb treatment. Most animals tested had a vigorous immune response to the injected MoAbs, both antiidiotypic as well as anti-isotypic antibodies were formed. This response was reduced by using Fab2 fragments or by additional immunosuppression, but it was still high enough to prevent further effectiveness of the MoAb treatment.

Animals↗