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Idiopathic Systemic Capillary Leak Syndrome (SCLS) is a rare entity characterised by idiopathic increasing of capillary permeability associated with recurrent attacks of hypovolaemic shock. We report the case of a 39-year-old man with a SCLS fourteen years after a cadaveric renal transplantation. The clinical evolution was rapidly fatal despite treatment with corticoids, aminophylline and terbutaline which are the most efficient drugs known to prevent attacks.

It is currently estimated that about 0.5% of patients will develop Kaposi's sarcoma (KS) after kidney transplantation. Tapering of immunosuppression often leads to KS remission, but also results in graft loss in more than 50% of cases. Whether retransplantation is safe in these patients is unknown. We here report on eight patients who developed KS recurrence after kidney transplantation-(A) Patients with previously treated KS: There were 4 patients who had clinical remission of KS (including three posttransplantation) for periods ranging from 5 months up to 19 years before transplantation. All 4 developed KS recurrence within months after transplantation. In 3 patients, KS regressed only when all immunosuppression was discontinued, at the price of allograft removal. Partial remission occurred in the fourth patient following reduction of immunosuppression and gancyclovir administration; (B) Patients with recurrent KS during a single transplant: 4 patients developed KS after transplantation that regressed following reduction of immunosuppressive therapy. Increased immunosuppression, in the form of steroid pulses in 3 patients was associated with recurrence of KS. Subsequent reduction of immunosuppression caused regression of KS in all 4 patients, but 2 recipients lost their allografts. These data emphasize the high risk of recurrence of KS after renal transplantation. If physicians decide to transplant patients with a history of KS, they should inform the future recipient of the possibility of KS recurrence.

In our experience the use of OKT3 as prophylaxis in renal transplantation has been associated with an increased incidence of both delayed graft function and thromboses of graft vessels. OKT3 nephrotoxicity might have been favored by restriction of perioperative fluid infusion to prevent pulmonary edema and by the use of very high dose (30 mg/kg) of methylprednisolone (mPDS) before the first OKT3 injection to reduce the release of cytokines. This led us to modify our perioperative management in three ways: (1) hydration status was optimalized; (2) the calcium-channel blocker diltiazem, considered beneficial for recovery of graft function, was administered on the day of transplantation; and (3) the dose of mPDS given before the first OKT3 injection was fixed at 8 mg/kg. Comparison of two consecutive series of patients (group 1, control patients, N = 172; group 2, managed as described above, N = 173) showed that: (1) the incidence of delayed graft function fell from 52% in group 1 to 22% in group 2 (P < 0.0001): (2) the incidence of pulmonary edema was not significantly increased in group 2 (3.5% vs. 1.7% in group 1, P = 0.5); and (3) the frequency of intragraft thrombosis fell from 7.6% in group 1 to 1.2% in group 2 (P = 0.0034). Multivariate analysis showed that the volemia/diltiazem program and avoidance of high mPDS dose were the most important factors responsible for the reduced occurrence of delayed graft function and graft vessels thrombosis, respectively. We conclude that a combined strategy of appropriate dosage of steroids before the first OKT3 injection, administration of a calcium-channel blocker and optimalization of volemia is safe and efficiently prevents against OKT3 nephrotoxic effects.

The use of OKT3 as prophylaxis in renal transplantation carries an increased risk of intragraft thrombosis, which is related to the systemic activation of the coagulation system that consistently occurs after the first dose of OKT3. As only a few patients develop thrombosis after OKT3 therapy, we searched for possible additional risk factor by comparing the demographic and clinical parameters of the 13 patients who developed thrombosis in our institution to those of 218 patients who did not. Multivariate analysis showed a relationship between the dose of methylprednisolone (mPDS) given before the first OKT3 injection and the risk of thrombosis: 6 out of 42 patients (14%) who received high (30 mg/kg) mPDS experienced a thrombotic event, as compared to 7 out of the 189 patients (3.7%) who received < or = 8 mg/kg of mPDS (P < 0.01). This led us to study the effects of mPDS on the procoagulant activity induced by OKT3 on peripheral blood mononuclear cells (PBMC) in vitro. The procoagulant activity of unstimulated PBMC (mean +/- SEM: 0.6 +/- 0.1 mU/ml) reached 3.0 +/- 0.7 mU/ml after OKT3 stimulation (P = 0.0062) and further increased to 7.4 +/- 2.0 mU/ml when PBMC were first preincubated overnight with mPDS before OKT3 stimulation (P = 0.018 as compared to OKT3 alone). This process involved the tissue factor/factor VII pathway, as shown by increased membrane expression of tissue factor on monocytes as well as by a marked reduction of the induced procoagulant activity when the clotting assay was performed with factor VII-deficient plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

We designed and performed on two patients a new surgical procedure of en bloc kidney and pancreatic transplantation. The liver, pancreas and kidneys were removed en bloc in the donor. On the bench, the liver and the left kidney were separated from the bloc, leaving the pancreas and the right kidney for combined kidney and pancreatic transplantation. The portal vein was divided near to the emergence of the splenic vein. The coeliac axis was taken with an aortic patch. The left renal vein was cut at its entrance to the inferior vena cava (IVC) and the left renal artery was taken with an aortic patch. Reconstruction of the pancreatic vessels was performed with a double anastomosis: the portal vein was anastomosed to the hole in the IVC resulting from the section of the left renal vein and the splenic artery was anastomosed to the hole in the aorta resulting from the section of the left renal artery. The proximal ends of the aorta and IVC were closed with running sutures. In the recipient, the iliac vessels on the right side were dissected. Anastomosis of the distal part of the aorta and the IVC was performed with the right iliac vessels. Duodenocystostomy and reimplantation of the ureter were done according to the usual techniques. This new surgical technique allowed an easy vascular reconstruction of the pancreatic vessels. In the recipient, only one side was used for renal and pancreatic transplantation. Moreover, the length of the transplant procedure was significantly reduced.

We observed a kidney transplant recipient in whom acute hepatitis was the initial manifestation of tuberculosis, preceding radiological lung involvement by several weeks. The diagnosis was suspected and treatment initiated based on the finding of a granulomatous hepatitis on liver biopsy. Mycobacterial tuberculosis was grown and identified first in liver samples and only later in sputum and bone marrow. This case illustrates the protean manifestations of tuberculosis in immunosuppressed patients.

We report the case of a 69-year-old woman who presented acute hepatitis due to Amanita Phalloides poisoning complicated of acute renal failure. Her clinical evolution was favorable under medical treatment whose actual modalities are discussed.

BALB/c mice neonatally injected with 1 x 10(8) (A/J x BALB/c)F1 hybrid spleen cells develop polyclonal B cell activation and autoimmune features as a consequence of a host-versus-graft (HVG) reaction. In this study, we first analyzed the time-course development of the renal lesions in HVG mice. From week 2 to week 6, linear deposits of IgG were observed by immunofluorescence along the glomerular capillary walls. From week 8 to week 12, the immunofluorescence pattern of IgG changed from linear to granular, and by immunoelectron microscopy, the IgG deposits were located on the epithelial side of the glomerular basement membrane (GBM). In addition, focal glomerulosclerosis complicated this membranous glomerulopathy in about 50% of the 12-week-old HVG mice and albuminuria was increased in most of them. Circulating antibodies to antigens of the GBM (laminin, type IV collagen) and of the renal tubular epithelial (RTE) cells (dipeptidyl peptidase IV, gp330) were already detected at week 2 and were still present at week 12. Immunoglobulins eluted from isolated glomeruli contained antibodies directed against type IV collagen, laminin, and to a lesser degree against gp330. F1 donor B cells were involved in the production of nephritogenic antibodies as indicated by (a) the presence of A/J allotypic determinants on serum anti-laminin antibodies and (b) the abrogation of the in vitro production of anti-GBM, anti-laminin and anti-RTE antibodies when spleen cells from HVG mice were depleted of F1 donor B cells. Finally, mixed lymphocyte culture experiments established that T cells from HVG mice stimulate normal B cells from F1 donor hybrids to produce anti-GBM, anti-laminin, anti-type IV collagen, anti-RTE, anti-gp330 and anti-dipeptidyl peptidase IV antibodies. We conclude that mice neonatally injected with semi-allogeneic spleen cells develop a glomerulonephritis characterized by the transition from a linear to a granular IF pattern, and that the production of nephritogenic antibodies results from the activation of donor B cells by host helper T cells.

BALB/c mice rendered tolerant to A/J alloantigens by neonatal injection of 10(8) (A/J X BALB/c)F1 spleen cells develop an autoimmune disease associated with a polyclonal activation of donor B cells. To study the mechanisms leading to donor B cell activation in tolerant mice, we prepared mixed lymphocyte cultures (MLC) between splenic T cells from neonatally injected mice and donor-type (A/J X BALB/c)F1 or third-party (C57BL/6 X BALB/c)F1 B cells. T cells from tolerized mice were unable to generate cytotoxic T lymphocytes, to proliferate or to secrete interleukin (IL)2 after stimulation with donor alloantigens in MLC. These T cell responses were present after MLC with third-party antigens, but were of lower intensity than those generated by control BALB/c T cells. In contrast, T cells from tolerized mice stimulated immunoglobulin production by donor-type (A/J X BALB/c)F1 B cells much more powerfully than T cells from control BALB/c mice. The stimulation of donor-type (A/J X BALB/c)F1 B cells was polyclonal, as attested by the levels of anti-hapten and anti-DNA antibodies in the MLC supernatants. IgM was the dominant isotype secreted in vitro, but IgG1 and IgG3 were also produced in significant amounts. Lysis experiments indicated that the T cells responsible for F1 B cell stimulation in MLC were CD4+ host T cells. These T helper cells were alloreactive since they did not stimulate syngeneic BALB/c B cells, and their effect on donor B cells was specifically blocked by anti-donor Ia monoclonal antibodies. Addition of anti-IL 4 monoclonal antibody to MLC between T cells from tolerant mice and (A/J X BALB/c)F1 B cells almost completely abolished the production of IgG1, but not that of IgM or IgG3. Taken together, these findings indicate that neonatal injection of alloantigens in BALB/c mice induces a state of dissociated tolerance, with unresponsiveness of anti-donor T cells secreting IL 2 on the one hand, and persistence of T cells responsible for B cell help and IL 4 secretion on the other hand.

BALB/c mice rendered chimeric at birth by injection of 10(8) (A/J X BALB/c)F1 spleen cells develop a lupus-like autoimmune disease linked to the activation of donor B cells by host T cells. As in vitro studies previously indicated that interleukin 4 (IL4) was a mediator of the interactions between T and B cells, we analyzed the intensity of Ia antigen expression on B cells of chimeric mice. Flow cytometric analysis with anti-Ia monoclonal antibodies (mAb) revealed that B cells from spleens and lymph nodes of 2-week-old chimeric BALB/c mice displayed a two- to threefold increase in membrane Ia antigen expression, this increase still being present in spleens of 30-week-old animals. An increase in Ia antigen expression was also found in the small number of donor B cells detected in spleens and lymph nodes of chimeric mice. IL4 was the major stimulus leading to increased B cell Ia antigen expression, as this phenomenon was substantially prevented by in vivo treatment of chimeric mice with the anti-IL4 11B11 mAb. In vitro experiments revealed that host splenic T cells of chimeric mice, while unable to generate anti-donor cytotoxic T lymphocytes, secreted significant amounts of IL 4 when stimulated in mixed lymphocyte cultures (MLC) with donor alloantigens. This IL4 secretion led to an increased expression of Ia antigens on donor-type F1 B cells present in MLC. No significant increase in Ia antigen expression was found on syngeneic BALB/c B cells co-cultured with T cells from chimeric mice unless A/J B cells were added to the cultures. Taken together, these findings indicate that increased Ia antigen expression on donor B cells is induced by IL4 secreted by anti-donor T cells. IL4 released in this setting also leads to increased Ia antigen expression on host B cells through a bystander effect.

The neonatal injection of semi-allogeneic spleen cells in mice induces a state of tolerance which can be demonstrated in mixed lymphocyte culture by the inability of T lymphocytes to proliferate, to secrete interleukin-2 and to generate cytolytic activities towards the injected alloantigens. Tolerant animals develop an autoimmune syndrome characterized by an antibody-mediated glomerulonephritis associated with high levels of IgE, IgG1 and anti-DNA antibodies. This syndrome is linked to the activation of B cells injected at birth by host T cells which escape tolerance induction. Interleukin 4 is one of the mediators of these lymphocytic interactions, which suggests that Th2 cells play an important role in this experimental model of autoimmune glomerulonephritis.