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V Donckier

Publications and source records attributed to V Donckier.

At least 37 records · Page 2Linked to original sources
PubMed1997

Long-term results after surgical treatment of renal hyperparathyroidism when fewer than four glands are identified at operation.

BACKGROUND: When fewer than four parathyroid glands are discovered during cervical exploration in cases of renal hyperparathyroidism, some have suggested that the glands could be resected and that no parathyroid tissue should be grafted. The aim of the present study was to evaluate this approach. Indeed, no detailed follow-up of such patients has been reported so far. STUDY DESIGN: Between September 1979 and July 1995, 157 patients underwent a cervical exploration for renal hyperparathyroidism in our department. In 23 cases, fewer than four parathyroid glands were found. The present study reports the results of 16 of these patients who did not undergo autotransplantation with parathyroid tissue after resection of all identified glands. RESULTS: At their last visit, four patients had normal blood levels of intact parathyroid hormone 14 to 71 months (median 60 months) after parathyroidectomy. The parathyroid hormone was not detectable in 2 patients at 16 and 76 months after operation. It was elevated in the 10 remaining patients, but the disease required no treatment or could be controlled medically in 7 patients with a follow-up ranging from 12 to 100 months (median 33 months). Two patients needed reoperation, one at 14 and one at 45 months after the first operation. An ectopic gland was found in both cases. The last patient refused further surgical treatment and died after 13 months. CONCLUSIONS: In most cases, autotransplantation of parathyroid tissue is not necessary when fewer than four glands are identified during parathyroidectomy. When grafting was omitted, 14 of 16 patients had normal or elevated blood levels of intact parathyroid hormone 10 to 100 months after parathyroidectomy (median 45 months). However, in two patients, intact parathyroid hormone was persistently undetectable for 16 to 76 months. This suggests that parathyroid tissue should be cryopreserved for delayed autotransplantation when the surgeon chooses not to graft parathyroid tissue.

Calcium↗
PubMed1997

Tolerance in liver transplantation: facts and perspectives.

Today, liver transplantation is the treatment of choice for most of the patients with endstage liver failure. Nevertheless, immunosuppressive regimens are not yet optimal; rejection still represents the first cause of graft loss, and infections and malignancies related to the non specific immunosuppression are a major source of morbidity and mortality. Therefore, the development of protocols aiming to induce transplantation tolerance--the survival of the graft without immunosuppression--represents a crucial challenge for the future. In the present report, we discuss two different approaches in this perspective. First, as compared with other organ, liver graft may present a particular propension to induce chimerism. As this phenomenon could promote allograft survival, the enhancement of chimerism by administration of donor cells, simultaneously with the transplantation, may constitute a new therapeutic strategy to induce tolerance. Second, experimental observations indicate that the initiation of the immune reaction in the liver may preferentially induce a TH2-type response. As TH2 lymphocytes are poor effector of acute rejection, this phenomenon could contribute to the spontaneous survival of liver graft and their tolerogenic effect observed under some experimental conditions. However, the capacity of TH2 cells to induce lymphoproliferative disease and their possible role in chronic rejection will probably represent a major limitation for clinical use of this strategy.

Animals↗
PubMed1995

Critical role of interleukin 4 in the induction of neonatal transplantation tolerance.

Neonatal injection of semiallogeneic cells is known to promote differentiation of donor-specific CD4+ T cells into TH2-like cells in the peripheral lymphoid organs. We reasoned that the propensity of neonatal T cells to synthesize high levels of IL-4 might be involved in this polarization of the alloreactive response and thereby in the development of neonatal transplantation tolerance. First, analysis of cytokine gene expression in lymph nodes after neonatal injection of 10(7) (A/J x BALB/c)F1 cells in BALB/c mice indicated that IL-4 but not IL-2 is rapidly produced by CD4+ cells after allogeneic challenge in vivo. To determine whether the early production of IL-4 was involved in the establishment of allotolerance, BALB/c mice neonatally injected with (A/J x BALB/c)F1 spleen cells received on days 1 and 3 after birth 1 mg of anti-IL-4 mAb (11B11) or the same amount of control mAb. When grafted with A/J skin at 4 weeks, 88% of mice treated with control mAb retained their graft for more than 50 days, whereas rejection occurred within 30 days in 93% of mice treated with anti-IL-4 mAb. Analysis of T cell functions after in vitro restimulation with A/J spleen cells indicated that early IL-4 neutralization did not prevent donor-specific CTL unresponsiveness but allowed the emergence of alloreactive T cells secreting increased levels of IL-2 and IFN-gamma. We conclude that early production of IL-4 is critical for the establishment of neonatal transplantation tolerance in this strain combination, which has disparities across the entire H-2 region.

Animals↗
PubMed1994

IFN-gamma prevents Th2 cell-mediated pathology after neonatal injection of semiallogenic spleen cells in mice.

BALB/c mice injected at birth with 10(8) (A/J X BALB/c)F1 hybrid spleen cells develop an autoimmune host-vs-graft (HVG) disease as a result of activation of donor B cells by host CD4+ cells. The antidonor CD4+ cells seem to be Th2-like cells, inasmuch as they are profoundly deficient in IL-2 and IFN-gamma production, but secrete high levels of IL-4 and IL-10. As IFN-gamma is known to inhibit the development of TH2 cells, we attempted to modulate HVG disease by injecting rIFN-gamma. First, we found that 10 micrograms of rIFN-gamma given on days 1 and 3 after birth reduced the serum hyper-IgE of HVG mice by 90% and the serum hyper-IgG1, by 70%. In addition, rIFN-gamma administration significantly decreased the anti-DNA IgG1 titers and prevented the occurrence of anti-glomerular basement membrane and anti-laminin IgG1 Abs as well as the formation of immune deposits in renal glomeruli. These effects were not caused by the abrogation of chimerism, as indicated by the persistence of donor-type B cells in lymph nodes and of Igs bearing donor allotype in serum. MLC experiments indicated that the major effect of early rIFN-gamma administration was to restore the production of IL-2 and IFN-gamma by donor-specific T cells while these cells still secreted significant amounts of IL-4 and IL-10. Unresponsiveness of antidonor cytolytic T cells was not influenced by rIFN-gamma. We conclude that rIFN-gamma prevents the TH2-type response induced by the neonatal injection of semiallogeneic spleen cells and the associated pathology.

Animals↗
PubMed1994

Modulation of the release of cytokines and reduction of the shock syndrome induced by anti-CD3 monoclonal antibody in mice by interleukin-10.

Since IL-10 was recently shown to inhibit several T cell functions in vitro, we investigated the effects of IL-10 on the cytokine release syndrome induced in mice by the 145-2C11 anti-CD3 mAb. As OKT3 in man, this mAb induces a massive polyclonal T cell activation before to induce immunosuppression. First, we found that administration of 1000 U of recombinant mouse IL-10 (mIL-10) 30 min before injection of 10 micrograms of the 145-2C11 antimouse CD3 mAb markedly reduced the systemic release of IFN-gamma and TNF. In contrast, IL-10 pretreatment did not significantly modify the release of IL-6. To determine the effect of IL-10 pretreatment on the endogenous secretion of IL-10 induced by the 145-2C11 mAb, mice were injected with human IL-10 (hIL-10) which does not cross-react in the ELISA for mIL-10 determination. While hIL-10 was as efficient as mIL-10 in reducing TNF and IFN-gamma release, it did not modify peak serum levels of IL-10. The modulation of cytokine production by mIL-10 was associated with a significant reduction of the toxicity of the 145-2C11 mAb, as assessed by the attenuation of hypothermia and by the reduced lethality in D-galactosamine-sensitize mice. We conclude that IL-10 differentially regulates the in vivo production of cytokines and decreases the systemic toxicity induced by the 145-2C11 mAb. These observations suggest potential therapeutic applications of IL-10 in organ transplantation, especially in association with anti-CD3 mAb.

Animals↗
PubMed1994

In vivo immunosuppression induced by a weakly mitogenic antibody to mouse CD3: evidence that induction of long-lasting in vivo unresponsiveness requires TcR signaling.

The use of anti-CD3 monoclonal antibodies (mAb) to treat allograft rejection has been complicated by the morbidity observed during the first days of treatment, secondary to T cell activation and cytokine release. Available evidence in a mouse model indicates that F(ab')2 fragments of an anti-CD3 mAb are not mitogenic in vitro and can be injected in vivo without apparent toxicity. However, their immunosuppressive capacity is dramatically reduced, suggesting that long-term immunosuppression mediated by anti-CD3 antibodies in vivo may be associated to their mitogenic capacity. This paper demonstrates that a poorly mitogenic anti-CD3 mAb is able to induce potent immunosuppression in vivo with reduced morbidity. This finding suggests that immunosuppression in vivo by anti-CD3 mAbs is not directly related to their activation properties but nevertheless requires signaling capacities. Therefore, immunosuppression in vivo may be best achieved by using antibodies able to deliver an incomplete activation signal to T cells (thus avoiding systemic cytokine release), possibly leading to anergy. The implications of this study for the development of immunosuppressive antibodies are discussed.

Animals↗
PubMed1993

Increased IL-6 production and IL-6-mediated Ig secretion in murine host-vs-graft disease.

BALB/c mice neonatally injected with semiallogenic (A/J x BALB/c)F1 splenocytes develop a host-vs-graft (HVG) reaction between host T cells and donor B cells, resulting in hypergammaglobulinemia, splenomegaly, and increased serum levels of various autoantibodies. This syndrome is associated with a polyclonal activation of the donor-derived B cells. High serum levels of IL-6 were found in 4-wk-old mice undergoing HVG disease (mean +/- SEM, 132 +/- 93 as compared with 12 +/- 2 in control mice, p < 0.05). Also supernatants of spleen cell cultures from HVG mice contained increased levels of IL-6. In situ hybridization and cell depletion experiments demonstrated that host macrophages were responsible for this pathologic IL-6 secretion. The spontaneous in vitro production of autoreactive antibodies by donor B cells from HVG mice was further enhanced by adding human rIL-6, whereas addition of human rIL-1 beta, human rIL-2, murine rIL-4, murine rIL-5, or combinations of these cytokines had no effect. Finally, addition of blocking anti-IL-6 and anti-IL-6 receptor mAb markedly reduced hyper IgG1 production in cultures of spleen cells from HVG mice. These data suggest that an increased production of IL-6 by persistently stimulated host macrophages is involved in the activation of donor B cells leading to HVG disease.

Animals↗
PubMed1992

Unusual splenic complication of acute pancreatitis.

Splenic complications of acute pancreatitis are rare. We describe a spontaneous subcapsular splenic laceration during an episode of acute pancreatitis, without any evidence of one of the currently reported predisposing factors. Its spontaneous resolution suggests that conservative therapy can be proposed in such complications.

Acute Disease↗
PubMedDate not supplied

Value of the MELD score for the assessment of pre- and post-liver transplantation survival.

The MELD score has now been implemented in the United States for liver allocation, but it has not been validated in Europe. Its association with posttransplant outcome is unclear. Optimal cutoff values of MELD and Child-Pugh scores to predict death on the liver waiting list were defined in a series of 137 cirrhotic patients listed for liver transplantation. Six-month actuarial survival while on the waiting list was 90% with a Child-Pugh <11 and MELD <17, whereas it decreased progressively to 40% at 6 months after listing for those having a Child-Pugh and MELD score >10 and >16. Analysis of a series of 112 patients (85 chronic liver disease and 27 hepatocellular carcinoma) revealed no change in MELD value at the time of transplantation compared to the score at the time of listing (mean +/- SD: 15.5 +/- 7.7 vs 15 +/- 5.8) with a mean waiting time of 118 days. Using either the optimal cutoff for MELD score (<17 or >16) or seven different strata (3 to 7, 8 to 10, 11 to 13, 14 to 16, 17 to 19, 20 to 22, 23 to 39), whether measured at listing or just before liver transplantation, there was no significant difference (chi(2) 4.97, P = .58) in survival: 82.7% and 63% at 6 and 60 months, overall. Our data confirm that the MELD score with only three parameters is as good as the Child-Pugh score to predict mortality on the Eurotransplant waiting list. The optimal cutoff to assess higher priority for the bad category is >16. There was no negative impact on short- or long-term prognosis of the bad categories of MELD.

Humans↗