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Biomedical subjects

P Kinnaert

Publications and source records attributed to P Kinnaert.

At least 37 records · Page 2Linked to original sources
PubMed1996

Renal transplantation exposes patients with previous Kaposi's sarcoma to a high risk of recurrence.

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.

Adult↗
PubMed1996

Monocyte procoagulant activity induced by in vivo administration of the OKT3 monoclonal antibody.

The first injection of OKT3 in kidney transplant recipients activates the common pathway of coagulation. This may result in early thrombosis of graft vessels. To this day, the cells involved in this phenomenon have not been identified. The aim of this study was to investigate whether circulating monocytes participated in this OKT3-induced coagulopathy. The procoagulant activity (PCA) of circulating monocytes rose from (mean +/- SEM) 0.15 +/- 0.02 mU/mL to 0.40 +/- 0.05 mU/mL at 3 hours (P = .002) and 0.56 +/- 0.21 at 5 hours (P = .045) after the initial OKT3 injection. These monocytes displayed increased tissue factor expression at the same moments (mean flourescence intensity: 14 +/- 2 before OKT3 injection versus 54 +/- 14 at 3 hours, P = .008 and 34 +/- 7 at 5 hours, P = .01). Tissue factor mRNA was detected in blood by reverse transcriptase-polymerase chain reaction as early as 2 hours after OKT3 administration. The circulating monocytes also displayed a steady increase in membrane expression upregulation of ICAM-1, CD29, CD11b, and CD11c. In vitro experiments showed that OKT3 as well as 2 mitogenic, humanized anti-CD3 antibodies potently induced monocytic PCA whereas the 4 nonmitogenic anti-CD3 antibodies tested were over 1,000-fold less potent than OKT3. We conclude that (1) OKT3 induces in vivo tissue factor gene upregulation and membrane expression resulting in increased PCA of circulating monocytes; and (2) nonmitogenic anti-CD3 antibodies seem devoid of significant procoagulant properties.

Blood Coagulation↗
PubMed1996

Role of CD18-dependent and CD18-independent mechanisms in the increased leukocyte adhesiveness and in the variations of circulating white blood cell populations induced by anti-CD3 monoclonal antibodies.

Anti-CD3 antibodies induce a quick and profound depletion of peripheral blood mononuclear cells (PBMCs) that is not well understood. We studied the effect of OKT3, a mouse monoclonal antibody against the human CD3 complex, on the in vitro adhesion of human PBMCs to monolayers of fresh and fixed human umbilical vein endothelial cells (HUVECs). OKT3 induced an increased adhesiveness of PBMCs. This phenomenon was blocked with anti-CD18 antibodies, indicating the participation of beta 2 integrins. As this increased adhesiveness could explain the lymphopenia by adhesion of PBMCs to endothelial cells and their sequestration in some peripheral vascular beds, we studied the effect of anti-CD18 antibodies in vivo on mice injected with 145/2C11, a hamster monoclonal antibody against murine CD3. Mice treated with 145/2C11 presented with a transient granulocytopenia and a sustained reduction in PBMCs. A monoclonal anti-CD18 antibody prevented the granulocytopenia but had no effect on the drop in PBMCs. Consequently, the in vivo depletion of PBMCs after administration of an anti-CD3 monoclonal antibody involves CD18-independent mechanisms, while the transient drop in polymorphonuclear cells appears to be CD18-dependent.

Adult↗
PubMed1996

OKT3 prophylaxis in renal grafts with prolonged cold ischemia times: association with improvement in long-term survival.

The data on patients participating in two randomized, prospective studies with similar immunosuppressive regimens were updated and combined to evaluate the long-term effects of OKT3 according to cold ischemia time (< or = or > 24 hr). Among 159 patients in the OKT3 and 153 in the cyclosporine A (CsA) group, 8 and 12 deaths occurred, respectively (P = NS). In patients with cold ischemia > 24 hours, OKT3 prophylaxis resulted in a lower mean number of rejection episodes per patient than did CsA prophylaxis within one year (mean +/- SEM: 0.87 +/- 0.11 vs. 1.35 +/- 0.14, respectively; P = 0.008) and within five years (1.07 +/- 0.12 vs. 1.49 +/- 0.15, respectively; P = 0.032). In contrast, rejection incidences in patients with cold ischemia < or = 24 hours was not significantly different in the two groups. In all study patients, there was a trend towards higher graft survival rates in the OKT3 group versus the CsA group (at 5 years, 73% vs. 66%, respectively; P = 0.182). Among recipients of kidneys with cold ischemia times > 24 hours, OKT3 patients had significantly higher graft survival than CsA patients at two years (84% vs. 64%, respectively) and at five years (71% vs. 56%, respectively; P = 0.045). Significant differences were not observed in recipients of kidneys with cold ischemia times < or = 24 hours. In conclusion, patients receiving renal grafts with long cold ischemia times strongly benefit from OKT3 prophylaxis.

Adult↗
PubMed1996

Direct activation of human peritoneal mesothelial cells by heat-killed microorganisms.

OBJECTIVE: The aim of the study was to determine if human peritoneal mesothelial cells (HPMCs) can be activated directly by bacterial products contained in preparations of heat-killed Escherichia coli and staphylococci. SUMMARY BACKGROUND DATA: It has been shown recently that cytokine-activated HPMCs produce the inflammatory mediators, interleukin-1, interleukin-6, interleukin-8, and macrophage chemotactic protein-1. Studies concerning the effects of bacterial products on HPMCs are scarce and have not yielded conclusive results. METHODS: Growth-arrested HPMC monolayers were prepared from cell suspensions obtained by enzymatic disaggregation of small pieces of omentum. They were incubated for 24 hours with heat-killed E. coli (ATCC 25922), heat-killed staphylococci (ATCC 25933), or E. coli lipopolysaccharide, and the release of various cytokines in the culture media was measured by radioimmunoassays or enzyme-linked immunosorbent assays. Results were expressed as mean +/- standard error of the mean in picograms per milliliter of supernatant and analyzed with the Wilcoxon test; p values of less than 0.05 were considered significant. RESULTS: Baseline production of interleukin-6, interleukin-8, the chemokine "regulated upon activation, normal T cell expressed and secreted" (RANTES), and macrophage chemotactic protein-1 varied widely from one omental preparation to the other. E. coli increased the release of these mediators: from 1206 +/- 316 pg/mL to 8480 +/- 2189 pg/mL for interleukin-6, from 285 +/- 58 pg/mL to 3164 +/- 1053 pg/mL for interleukin-8, from 7 +/- 5 pg/mL to 684 +/- 264 pg/mL for RANTES, and from 2212 +/- 346 pg/mL to 7726 +/- 1473 pg/mL for macrophage chemotactic protein-1. Heat-killed staphylococci did not alter significantly the production of RANTES or macrophage chemotactic protein-1 but increased the production of the two other cytokines from 1325 +/- 389 pg/mL to 2206 +/- 523 pg/mL for interleukin-6 and from 318 +/- 70 pg/mL to 819 +/- 265 pg/mL for interleukin-8. CONCLUSIONS: The authors' results show that HPMCs are able to react to a direct stimulation with heat-killed microbes. They suggest that HPMCs, as well as resident macrophages, participate actively in the initiation and possibly in the modulation of intraperitonen inflammatory reactions.

Chemokine CCL2↗
PubMed1996

Prevention of OKT3 nephrotoxicity after kidney transplantation.

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.

Adult↗
PubMed1995

Influence of donor-recipient HLA-DR mismatches and OKT3 prophylaxis on cadaver kidney graft survival.

Previous studies from our center have shown that donor-recipient HLA-DR mismatches (MM), characterized by the presence of the DR antigen in the donor but not in the recipient or vice versa, are associated with differential effects on graft survival (GS): some of them are beneficial (BEN) with results similar to those of HLA-DR identical or compatible pairs (85% 18 months GS) and some are detrimental (DET) (64% 18 months GS), whereas the other MM, neither BEN nor DET (neutral [NEU]) yield intermediate results (78% 18 months GS). The aim of the present study was to update the results at a longer follow-up time and to assess whether they are influenced or not by prophylactic administration of anti-CD3 mAb (OKT3). The analysis of 234 transplantations performed from 1980 to 1994 with only 1 HLA-DR MM confirmed the BEN effects of HLA-DR5 in either the donor or the recipient and the DET effects of HLA-DR1 or -DR2 in the donor and of HLA-DR2 or -DRW6 in the recipient. These effects were independent of those exerted by other, HLA-DR not related, prognostic factors. The transplants with 1 HLA-DR MM were then compared with those with zero HLA-DR MM (n = 378) and 4 groups were formed according to 2 levels of HLA-DR MM (zero or BEN MM vs. NEU or DET MM) and immunosuppression (with vs. without OKT3 prophylaxis). GS at 5 years was 63% in the group with either zero or BEN MM as compared with 41% in the group with either NEU or DET MM in the absence of OKT3 prophylaxis (P < 0.02); in comparison, with OKT3 prophylaxis, GS at 5 years was 73% in the group with either zero or BEN MM as compared with 58% in the group with either NEU or DET MM (P = 0.07). We conclude that the differential effects of HLA-DR MM on GS are still observed under OKT3 prophylaxis, that the effects of HLA-DR and immunosuppression on graft outcome are additive, and that OKT3 induction therapy is superior to therapy without OKT3. These observations could have important implications for the allocation policy and management of renal transplants.

Adult↗
PubMed1994

Elbow arteriovenous fistulas for chronic haemodialysis.

Arteriovenous fistulas (AVFs) were created at the elbow, rather than using prosthetic grafts, when forearm vessels were inadequate. A total of 272 such fistulas were constructed: 49 between the brachial artery and a forearm vein, 91 between the brachial artery and the elbow perforating vein, 52 between the brachial artery and the cephalic vein and 80 between the brachial artery and the basilic vein. In each case the vein was sutured end to side to the artery. The immediate failure rate was 11.8 per cent. The 1- and 4-year cumulative patency rates were 68.7 and 51.2 per cent for brachial artery-forearm vein AVFs, 80.3 and 68.0 per cent for those between the brachial artery and the elbow perforator, 74.1 and 61.3 per cent for brachial artery-cephalic vein fistulas, and 76.7 and 49.2 per cent for those between the brachial artery and the basilic vein. The elbow AVF is a reliable means of establishing vascular access for haemodialysis.

Adolescent↗
PubMed1994

OKT3 serum levels as a guide for prophylactic therapy: a pilot study in kidney transplant recipients.

The use of OKT3 as prophylaxis in renal transplantation results in a reduced incidence of graft rejection and appears to have beneficial effects on long-term kidney graft survival. However, we and others have observed that patients still experience rejection during the period of OKT3 prophylaxis given at the regular 5 mg/day dose. Many of these patients had no circulating CD3+ cells at the time of rejection, but their OKT3 serum levels were distinctly low (< 500 ng/ml). This led us to adjust OKT3 doses (5 or 10 mg) daily, according to the patients' OKT3 levels, in order to maintain an OKT3 concentration of around 1000 ng/ml. In addition, patients were randomized to receive either 5 mg (group 1, n = 15) or 10 ng (group 2, n = 14) OKT3 as the initial three doses. Concomitant immunosuppression consisted of azathioprine and steroids, with the introduction of cyclosporin A on day 11. Patient survival was 100% after 3 months of follow-up. The intensity of OKT3 first-dose reactions was similar in both groups. Intragraft thrombosis, initially observed in a previous group of patients who received a fixed 10 mg/day OKT3 prophylaxis, occurred in three patients in group 1 and resulted in two graft losses. The cumulative OKT3 dose was similar in both groups (mean +/- SEM 98 +/- 2 mg in group 1 vs 102 +/- 3 mg in group 2) and higher than the 70 mg usually administered. Group 2 patients had higher OKT3 serum levels during the first 4 days of therapy. No correlation could be found between patient weight and cumulative OKT3 dose (r = 0.29).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Tuberculosis presenting as acute hepatitis in a renal transplant recipient.

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.

Acute Disease↗
PubMed1994

High-dose glucocorticosteroids increase the procoagulant effects of OKT3.

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)

Adolescent↗
PubMed1994

Combined pancreatic and kidney transplantation: en bloc retrieval and transplantation--a new surgical technique.

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.

Anastomosis, Surgical↗