Search PubMed⌕ Search

Biomedical subjects

J Dantal

Publications and source records attributed to J Dantal.

At least 55 records · Page 3Linked to original sources

Renal transplantation from cadaver donors over 60 years old.

The influence of donor age on the short- and long-term outcome of cadaveric kidney transplantation was analyzed at our institution. During a 6-year period, 34 and 806 patients underwent kidney transplantation from cadaver donors over or less than age 60, respectively. Graft and patient survivals were compared throughout follow-up and herewith reported. In addition, main medical and surgical complications among recipients of elderly cadaver donors are detailed.

Adult↗

[Anti-cytokines and anti-cytokine receptors].

Cytokines play a key-role in the immune response. The best known of them is interleukin-2 and its specific receptors. Monoclonal antibodies directed against the interleukin-2 receptor have initially enabled this receptor to be characterized; then they served to confirm the major role played by this cytokine in immune responses, where it proved effective in many animal models such as allograft reaction, delayed hypersensitivity reaction and some experimental auto-immune diseases. These results have been confirmed in man, particularly in kidney transplantation (but also in bone marrow transplantation), and they encourage to develop new bioreagents (chimeral antibodies, "humanized" antibodies, fusion proteins). Some of these reagents are now undergoing evaluation in renal transplantation. The principles of these bioreagents, issued from molecular biology, can be applied to other cytokines involved in the immunopathological mechanisms of certain diseases such as, for example, IL-6 and its role in the development of myeloma. Data from immune intervention directed against other cytokines are, for the moment, preliminary, but many potential targets (IL-1, IL-4, TNF alpha, INF gamma) are emerging.

Animals↗

Prospective randomized comparison of University of Wisconsin and UW-modified, lacking hydroxyethyl-starch, cold-storage solutions in kidney transplantation.

University of Wisconsin cold storage solution differs from Euro-Collins by the presence of adenosine, allopurinol, and hydroxyethyl starch, which maintains osmotic pressure. It is now experimentally and clinically well established that the use of UW solution is associated with better liver graft recovery parameters after prolonged cold ischemia time. However, it has been also suggested in animal experiments that HES might not be essential for optimal kidney preservation, at least when cold ischemia time remains within 48 hr. Herein, we present a randomized study comparing UW (n = 44) and a modified UW (UW-mod) (n = 44) solution lacking HES, adenosine, and allopurinol on kidney graft recovery parameters. Forty-one consecutive Euro-Collins flushed kidneys, transplanted immediately before this randomized trial, were used as historical controls. The results indicate that UW-mod was as efficient as UW in preserving the kidney in cold ischemia ranges that did not exceed 48 hr. Both solutions (UW and UW-mod) seemed more effective than Euro-Collins, based on the analysis of several parameters including the number of days until the creatinine was < 300 microM (P < 0.05), the level of the serum creatinine at one month (P < 0.02), and the Cockroft index (P < 0.04). Since UW-mod is three times less expensive than UW, we suggest that the simplified solution could be routinely used to preserve kidneys for transplantation.

Adenosine↗

Evidence that early acute renal failure may be mediated by CD3- CD16+ cells in a kidney graft recipient with large granular lymphocyte proliferation.

We report here on a patient with a large granular lymphocyte proliferative disease who received a third kidney allograft. This patient presented a lymphocytosis (culminating at approximately 30,000/mm3) with a large proportion (approximately 70%) of CD3- WT31- CD2+ CD16+ lymphocytes. Five days after a kidney graft and during prophylactic treatment by Ortho pan OKT3, he presented an acute graft failure with an apparent interruption of graft blood flow as assessed by the Tc99 scan pattern and an arteriogram. The biopsy showed an abnormal accumulation of intravascular CD3- CD16+ cells bound to endothelial cells with thrombilike patterns in small and middle-sized arteries, whereas CD3+ mononucleated cells infiltrate was restricted to interstitium as observed in his previous graft, performed before the appearance of the lymphoproliferative disorder. The syndrome resolved spontaneously. The role of OKT3-mediated release of cytokines able to upregulate endothelial cell adhesion molecules in triggering this phenomenon is discussed.

Acute Kidney Injury↗

Effects of plasma-protein A immunoadsorption on idiopathic nephrotic syndrome recurring after renal transplantation.

Patients with end-stage renal failure secondary to idiopathic nephrotic syndrome are at risk of initial disease recurrence after kidney transplantation (30%). Selective proteinuria can appear immediately after transplantation and focal glomerular sclerosis with graft loss can occur in 10% of patients with recurrence. Current immunosuppressive protocols do not seem to influence the recurrence rate in adult patients and the efficacy of therapeutic plasma exchanges remains controversial. We have previously demonstrated that plasma exchanges, proposed early before glomerular sclerosis, were able to significantly reduce proteinuria without affecting albuminemia or glomerular filtration. We report here on three patients who suffered immediate recurrence after transplantation and were treated with plasma immunoadsorption onto protein A column (Excorim, Lund); these patients had prior histories of steroid-resistant focal glomerular sclerosis. This procedure is more specific than plasma exchange in that it cleared the serum of immunoglobulins, significantly decreased proteinuria in only two cases (from 14 to 5 g/d and 2.5 to 0.8 g/d) and eliminated it in the third case (from 3 to 0.1 g/d). The modifications of proteinuria levels appeared as early as the second immunoadsorption sequence and returned to pre-immunoadsorption values within 2 to 8 weeks. These observations argue for the protein A binding of plasmatic factor(s) involved in idiopathic, nephrotic syndrome and allow us to progress to the characterization of this(ese) factor(s).

Adult↗

Effect of the number of pregraft blood transfusions in kidney graft recipients treated with bioreagents and cyclosporin A.

The impact of a systematic, nondonor-specific, pregraft blood transfusion (BT) protocol was evaluated retrospectively in 446 consecutive, first renal transplant recipients with regard to graft survival rate, rejection, and incidence of infectious episodes. Cyclosporin A was the maintenance immunosuppressive treatment in all patients after a 2-week course of antithymocyte globulin or anti-IL-2 monoclonal antibody. Recipients were assigned to three groups according to the number of pregraft BT (one or two, three or four, or more than four). When nonimmunological failures were excluded from the study, patients receiving three or four BT had statistically better graft survival (P less than 0.02) and a lower incidence of rejection episodes (P less than 0.05) than those in the other groups. There were no significant differences between the three groups in the distribution of HLA mismatching (A, B and DR), time interval between the last BT and transplantation, DR6 recipient phenotype, or nonimmunological failures. Our results show that the number of pregraft BT is an important factor in transplantation.

ABO Blood-Group System↗

Use of monoclonal antibodies in human transplantation.

Monoclonal antibodies are of growing importance in human organ transplantation in the prophylatic and curative treatment of cellular rejection. Among the pan T-lymphocyte monoclonal antibodies, OKT3 has been much studied, although clinical research is engaged with more selective targets of allorecognition and/or their consequences, for example monoclonal antibodies directed against the interleukin-2 receptor, adhesion molecules and CD4 molecules. We summarize the use of these monoclonal antibodies and bioreagents in clinical transplantation.

Animals↗

Cluster-function relationship of rat-antimouse P55 IL-2 receptor monoclonal antibodies. In vitro studies of the CTL-L2 mouse cell line and in vivo studies in a delayed-type hypersensitivity model in mice.

Monoclonal antibodies directed against the P55 component of the interleukin 2 receptor (IL-2-R) have been used to prevent allograft rejection in various animal models, including primates and man. This study compares the functional effects of seven MoAbs directed against the mouse IL-2-R P55 chain both in vitro using the mouse CTL-L2 cell line and in vivo in a sheep red blood cell-induced delayed-type hypersensitivity model. Data from in vitro studies showed that a cluster of four MoAbs (cluster I: 5A2, 125, 135 [IgG2a] and AMT13 [IgG2b]) competed with IL-2 for binding to the P55 chain and caused an inhibition of IL-2-induced proliferation on CTL-L2. The respective dissociation constants (Kd) of the four MoAbs were 1.1, 1.4, 2.5, and 5.5 nM, and they all displayed a common maximal binding capacity of 2 x 10(5) sites per cell on CTL-L2. None of these MoAbs were found to fix rabbit complement. The three other MoAbs (2E4: IgG2a, 7D4: IgM, PC61: IgG1) with respective Kd of 0.8, 0.2, and 0.85 nM and maximal binding capacities of 2 x 10(5), 4 x 10(5) sites per cell did not interfere with IL-2 binding and did not affect the IL-2-induced proliferation of the murine cell line. All three MoAbs were found to define three separate epitopic clusters independent of cluster I. Among them, only 2E4 induced a strong complement-mediated cytotoxicity. In vivo experiments showed that all MoAbs from cluster I were efficient in suppressing the DTH reaction and that the magnitude of their effect was consistent with their respective Kds. At a suboptimal dose of 1 microgram per day, the DTH inhibition indices were 40%, 43%, 23%, and 9% for 5A2, 125, 135, and AMT13, respectively. The 2E4 MoAb was found to be as efficient as cluster I MoAbs in suppressing DTH (53% inhibition at 1 microgram/day) while 7D4 and PC61 induced only a moderate inhibitory effect (37% inhibition for each MoAb given at 10 micrograms/day, compared with 70% inhibition for cluster I MoAbs). Taken together, our results indicate that blocking the IL-2/IL-2-R interaction without complement fixation is sufficient per se to attenuate the DTH reaction, and conversely that strong complement-mediated cytotoxicity in the absence of a functional effect in the IL-2/IL-2-R interaction is also effective in this system. Finally, no synergistic effect between MoAbs belonging to different clusters was evidenced in the DTH model.

Animals↗