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Biomedical subjects

J Pirenne

Publications and source records attributed to J Pirenne.

At least 91 records · Page 5Linked to original sources

Evidence for free radical formation during human kidney transplantation.

Fourteen patients undergoing kidney transplantation were studied for evidence of the production of free radicals as assessed by the measurement of vitamin E (an index of lipid peroxidation) and of myeloperoxidase (a marker of neutrophil activation) in the systemic blood. Early (2 min) and late revascularization (30 min) of the kidney were respectively associated with a significant decrease of 35.5 and 40% of the initial level of plasma vitamin E. This consumption paralleled to the decrease of the vitamin E/total lipids ratio, a better indicator of vitamin E status. Heparin administration preceding renal artery clamping resulted in a twofold significant increase of baseline plasma myeloperoxidase (MPO) level (523 +/- 214 ng/ml). At kidney reperfusion, MPO concentration rose again and reached a maximum value of 1,653 +/- 882 ng/ml, indicating the presence of considerable neutrophil activation. A return to the baseline value was observed after 30 min of reperfusion. A short discussion about the possible origin of this MPO increase is given. Taken together, these data strongly suggest that free radical production, leading to lipid peroxidation phenomena, can occur within the early phase of kidney revascularization. Preliminary data using electron spin resonance with the spin-trapping technique strengthen this hypothesis.

Adult↗

Intraoperative cytokines production during orthotopic liver transplantation.

In summary, we established that a significant production of the monokines interleukin-6, tumor necrosis factor apha, and interleukin-1 occurred during orthotopic liver transplantation whereas the lymphokines interferon gamma and interleukin-2 were not detected. Levels of interleukin-6 reached their maximum values before and especially at the end of the anhepatic phase. They remained high after the anhepatic phase, i. e. after reperfusion of the new livers. Tumor necrosis factor alpha and interleukin-1 reached their maximum values after the anhepatic phase. Not only were interleukin-6, tumor necrosis factor alpha, and interleukin-1 present in the serum but they could also be detected in the bile produced by these new livers. Mechanisms of monokine production during orthotopic liver transplantation is multifactorial in origin and further studies will have to evaluate the relative contribution of the various factors involved. The possibility of an association between peroperative monokines and transplant outcome and their potential clinical implication will have to be elucidated.

Cytokines↗

Direct stimulation of cytokines (IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood. I. Comparison with isolated PBMC stimulation.

Production of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), interferon gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after stimulation by lipopolysaccharide (LPS) and phytohemagglutinin (PHA) was studied in 1/10 diluted whole blood (WB) culture and in peripheral blood mononuclear cell (PBMC) culture. Cytokines IL-1 beta, TNF-alpha and IL-6 are preferentially stimulated by LPS whereas IL-2, IFN-gamma and GM-CSF are stimulated by PHA. Combination of 5 micrograms/ml PHA and 25 micrograms/ml LPS gave the most reliable production of the six cytokines studied. IL-1 beta, TNF-alpha and IL-6 represent a homogeneous group of early-produced cytokines positively correlated among themselves and with the number of monocytes in the culture (LeuM3). Furthermore, IL-1 beta was negatively correlated with the number of T8 lymphocytes. IL-2, IFN-gamma and GM-CSF represent a group of late-produced cytokines. Kinetics and production levels of IL-6 and GM-CSF are similar in WB and PBMC cultures. In contrast, production levels of TNF-alpha and IFN-gamma are higher in WB than in PBMC whereas production levels of IL-6 and IL-2 are lower in WB than in PBMC. Individual variation in responses to PHA + LPS was always higher in PBMC cultures than in WB cultures. The capacity of cytokine production in relation to the number of mononuclear cells is higher in WB, or in PBMC having the same mononuclear cell concentration as WB, than in conventional cultures of concentrated PBMC (10(6)/ml). Because it mimics the natural environment, diluted WB culture may be the most appropriate milieu in which to study cytokine production in vitro.

Adult↗

Multiorgan transplantation in the rat: development of a new microsurgical model.

Although transplantation of multiple abdominal viscera (MOTx) has been performed in humans, reproducible animal models and extensive laboratory work are needed to explore the physiological and immunological aspects of this new transplant procedure. We therefore developed a microsurgical model that allows en bloc transplantation of three major abdominal viscera. Using isogeneic rat strain combinations, 30% of the liver, pancreas, and duodenum and a segment of small bowel (SB) were heterotopically transplanted. A segment of aorta that included the celiac axis and the superior mesenteric artery provided the blood supply to the graft. Venous outflow occurred via the graft suprahepatic vena cava into the recipient's infrahepatic vena cava. The graft SB was anastomosed to the native SB. After a training period (N = 15), we could achieve a success rate of 83% (N = 23). Mean operation time was 105 minutes. Macroscopic and microscopic appearance of transplanted organs was normal. This study documents the feasibility of MOTx in the rat and provides a microsurgical model that should facilitate preclinical experimental research in this area.

Animals↗

Graft-versus-host disease after multiorgan transplantation.

A rat model of multiorgan transplantation (MOTx) including the liver, pancreas, duodenum, and variable segments of small bowel (SB) was used to ascertain whether graft-versus-host disease (GVHD) could be produced by this procedure. Rats receiving an isogeneic multiorgan transplant (MOT) survived more than 150 days. MOTx was then performed in the Lewis to (Lewis x Brown Norway) LBNF1 semiallogeneic combination, ensuring unidirectional GVHD. En bloc transplantation of the liver, pancreas, duodenum, and entire jejunum provoked lethal GVHD in all animals, and the mean time to recipient death (MT) was 16.5 +/- 0.43. When only one-half of the jejunum was included in the MOT, lethal GVHD similarly occurred in 100% of animals and the MT was 18 +/- 0.86. Finally, when only liver, pancreas, and duodenum were transplanted, the incidence of lethal GVHD was reduced to 50% (P less than 0.1). In those rats that died of GVHD, MT was 16 +/- 0.33. Fifty percent of the rats in this group, however, recovered from a milder form of GVHD and survived more than 150 days. These results demonstrate that MOTx induces GVHD and that the lethality of this process correlates with the inclusion of the SB in the graft and thus, with the overall amount of transplanted lymphoid tissue.

Animals↗

Resistance to graft-versus-host disease following small bowel transplantation.

Transplantation of a Lewis rat small bowel allograft (SBTx) into Lewis x Brown Norway F1 (LBNF1) hybrid recipients provokes lethal graft-versus-host disease. GVHD in F1 hybrid rats inoculated with large number of parental lymphocytes may be abrogated by prior treatment of F1 hybrids with a sublethal dose (SLD) of the same parental lymphocytes. Therefore, we sought to determine whether this type of immunomodulation would prevent GVHD after SBTx. We examined whether pretreatment of LBNF1 recipients with a SLD of parental lymphocytes, or with a revascularized segment of parental small bowel, might ameliorate GVHD following transplantation of the entire parental small bowel. Nonpretreated LBNF1 recipients died of GVHD after entire Lew SBTx; 95% of LBNF1 recipients pretreated with SLD of Lew lymphocytes and 84% of LBNF1 recipients first transplanted with a segment of Lew small bowel survived GVHD induced by entire Lew SBTx 10 days later. Of LBNF1 recipients pretreated with SLD of Brown Norway lymphocytes or first transplanted with a segment of BN small bowel, none were protected from GVHD induced by entire Lew SBTx 10 days later. We concluded that pretreatment of LBNF1 recipients either with an SLD of parental lymphocytes or with a segment of parental small bowel provides profound protection from the effects of GVHD following transplantation of an entire small bowel of the same parental strain specificity.

Animals↗

Rat kidney transplantation update with special reference to vesical calculi.

A technical update on rat kidney transplantation is given. In this study, the bladder-bladder union was made using silk, polyglycolic acid (Dexon), polyglactin (Vicryl), and chromic catgut. The propensity of these sutures to form vesical calculi was investigated in both first and second generation transplants. The results of our study indicate that there is no significant difference (P greater than 0.01) in their calculogenic ability. Special problems attendant with first and second generation kidney transplants are described. The concept and technique of second generation kidney transplants are also described.

Animals↗

Arterialization of the liver. III. Influence of systemic and portal pressure gradients following heterotopic partial liver transplantation.

An acute study was designed to compare blood pressures across a heterotopically transplanted partial liver graft using arterialized and nonarterialized models. Eight partial liver transplants (PLT) were done in each group, using Wistar rats. The data gathered from them are the basis for the results obtained herein. Whereas there was no significant difference (P greater than 0.01) in inflow, outflow, or the pressure difference across the PLT between nonarterialized and arterialized groups, host portal venous pressures were significantly higher (P less than 0.01) in the arterialized group. A 1 mm arteriovenous fistula (AVF) was used to arterialize the PLTs in this study. It was proved that arterializing a PLT using a 1 mm AVF did not alter the pressure difference across the transplanted liver compared with the situation in the nonarterialized setting.

Animals↗

Influence of the length of the small bowel graft on the severity of graft versus host disease.

The influence of the length and origin of a small bowel graft on graft versus host disease (GVHD) was studied in 33 (Lewis x brown Norway) F1 hybrids transplanted with different types of Lewis small bowel grafts. Recipients of an entire small bowel graft (N = 9), a jejunal graft (N = 6), or an ileal graft (N = 6) displayed a similar acute lethal GVHD, with 100% mortality rate and equivalent survival time (15 +/- 0.7, 16.8 +/- 0.9, and 16 +/- 0.6 days, respectively) (P greater than 0.01). On the other hand, 80% of the recipients of a segmental jejunal graft (N = 10) recovered from a transitory form of GVHD and regained weight similarly to the isografted rats (N = 4). It was concluded that the entire small bowel, jejunum, and ileum can provoke an equivalent GVHD after transplantation, whereas a segment of jejunum decreases the intensity of GVHD, probably by reducing the amount of transplanted lymphoid tissue.

Analysis of Variance↗

[Value and limits of bypassing the distal ileum in the treatment of hypercholesterolemia].

Partial ileal bypass (PIB) was performed in 8 young adults (5 males and 3 females, mean age 37 +/- 5 years) with a history of vascular surgery (aorto-coronary bypass, ACB, n = 6; stroke, n = 2), presenting with hyperlipidemia (II B: n = 7; IIA: n = 1). None of the patients had diabetes, 2 had mild hypertension, and all were cigarette smokers. Hypolipidemic drugs were discontinued prior to PIB. Following bypass surgery, patients received vitamin B12 injections twice monthly. Total plasma cholesterol (TPC) and total plasma triglycerides (TPT) were assayed at 3 months and 1 year after surgery. The mean follow-up period was 84 months. Mean TPC level was significantly lower (3.96 +/- 0.57 preoperatively vs 2.19 +/- 0.79 (p less than 0.001) and 2.54 +/- 0.76 (p less than 0.01) 3 months and 1 year postsurgery, respectively. Mean TPT level was significantly lower 3 months after the intervention (4.85 +/- 2.37 vs 2.33 +/- 0.62, p. less than 0.02), but not after one year. Similar trends were observed throughout the follow-up period. One of the ACB patients died of drowing, while three others had recurring angina pectoris symptoms. Coronary angiography showed that, despite low TPC levels, coronary artery disease had extended either to other vessels not included in the former bypass, or beyond the anastomoses. Patients with a history of stroke were asymptomatic. PIB is effective in normalizing TPC. Nonetheless, this isolated procedure is insufficient to prevent the evolution of multifactorial atherosclerosis.

Adult↗