Perioperative immune modulation.
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Biomedical subjects
Publications and source records attributed to P Kinnaert.
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OBJECTIVE: To find out if contact with Escherichia coli had any effect on a subsequent inflammatory reaction induced by the same micro-organism. DESIGN: Controlled laboratory study. SETTING: University laboratory. MATERIAL: Male white Wistar rats divided into groups of 6 to 10. INTERVENTIONS: Pretreatment with sponges soaked in 1 x 10(9) heat killed E. coli inserted either subcutaneously into the back or intraperitoneally into the right hypochondrium, and 14 days later repeat challenge. Controls received sponges soaked either in saline with penicillin and streptomycin or with carrageenan lambda. Pretreatment with live or heat killed E. coli or E. coli endotoxin injected intradermally or intraperitoneally (controls were given saline). MAIN OUTCOME MEASURES: Number of white cells present in the inflammatory infiltrate and the peritoneal cavity, and titres of anti-E. coli antibody. RESULTS: Pretreatment of Wistar rats with heat-killed or live E. coli (ATCC 25922) was followed by increase in the cellular infiltrates at the site of subsequent challenge with the same micro-organism. The effect was not related to the synthesis of anti-E. coli antibodies. CONCLUSION: Surgical patients have commonly been in previous contact with E. coli; this might affect their inflammatory reactions if they came into contact with the organism after operation. Further studies are needed to clarify the precise mechanisms and clinical relevance of these findings.
In a continuous series of 439 parathyroidectomies for primary or secondary hyperparathyroidism, 36 cases were reoperations. The initial operation had been a prior parathyroid exploration (PTx) in 17 cases, a thyroidectomy (Tx) in 17 cases, both operations in two cases. The incidence of parathyroid glands discovered at exploration was lower in both types of reoperations (67% after Tx, 72% after PTx) than in patients who were explored for the first time (94%). Anatomical variations and parathyroid pathologies were comparable in patients reoperated after Tx and in those explored for the first time. In patients reoperated after PTx, anatomical abnormalities (46% of glands in ectopic locations, 12% of supernumeray glands) and multiglandular pathologies (56% of hyperplasias) were much more frequently encountered. Long term results were satisfactory in patients explored for the first time (98% cures) and in reoperations after Tx (94% cures), but were less favourable in reoperations after PTx (78% cures).
When hyperparathyroidism recurs in patients previously treated by total parathyroidectomy and intramuscular parathyroid autotransplantation, excision of the graft is not always technically easy and it is often necessary to resect the portion of the muscle containing the implants. During November 1986, we began a program to test the feasibility of presternal subcutaneous autotransplantation of parathyroid tissue. We hoped this technique would make removal of the grafts simpler. Thirty-six patients with renal hyperparathyroidism (RHPT) received subcutaneous parathyroid implants. Persistent or recurrent hyperparathyroidism was observed in three patients during the follow-up period. The presence of active parathyroid tissue was demonstrated after some time in all the patients. The parathyroid implants were easily excised in three instances (one persistent RHPT and two recurrences). Microscopic examination of the resected specimens did not show any sign of malignant transformation. We conclude that presternal subcutaneous implantation of parathyroid tissue after total parathyroidectomy is a quick, safe and efficient surgical procedure in the treatment of RHPT.
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Among 93 consecutive kidney-transplant patients who received prophylactic OKT3 10 mg/day for 2 weeks, 9 had intragraft thromboses within 2 weeks of transplantation. The thromboses were in graft artery in 1 patient and veins in 3. The other 5 had thromboses in glomerular capillaries and thrombotic microangiopathy similar to that of haemolytic-uraemic syndrome. All attempted treatments failed, and the 9 grafts had to be removed. The finding that plasma concentrations of prothrombin fragment 1 and 2 were higher 4 h after the first OKT3 dose in OKT3 recipients than in transplant patients who received other prophylaxis (mean 5.88 [SEM 0.76] vs 2.25 [0.59] nmol/l, p less than 0.01) confirms that OKT3 has procoagulant effects in vivo.
In this prospective randomized study, acute renal transplant rejections occurring in patients who received prophylactic OKT3 therapy were treated with either 3 pulses of 8 mg/kg methylprednisolone (MPS) in an alternate-day regimen (total dose 25 mg/kg in 1 week, H group, n = 24) or 5 daily pulses of 3 mg/kg MPS (total dose 17 mg/kg, L group, n = 22). Acute rejection was proven by biopsy in more than 85% of cases in both groups. No difference was observed in rejection reversal (H 88%, L 91%), graft losses in the following 3 months (H 11%, L 4%) or the time evolution of the serum creatinine levels. The number (H 14, L 21) as well as the nature and severity of infections were similar in both groups. Only one death occurred in a patient who received OKT3 rescue therapy for corticoresistant rejections and developed Epstein-Barr virus (EBV)-related lymphoma. In conclusion, low dose MPS pulses appear as effective and safe as a higher dose to reverse acute rejection occurring after OKT3 prophylaxis. Thus, we favour the use of the low dose regimen in these patients.
Donor-recipient incompatibility (D + R -) for HLA-DQ1, but not for -DQ2 or -DQ3, is associated with an adverse effect on cadaver kidney graft survival. Until now, however, DQ1 recipients of DQ1-negative kidneys (D - R +) have not been differentiated from DQ1-identical donor-recipient pairs (D + R +) and splits of DQ1, DQ5 and DQ6, have not been studied in that respect. From our data (480 transplantations performed from January 1980 to December 1990), three donor-recipient DQ combinations (D + R +, D - R +, D + R -) were formed for each of four DQ specificities (DQ2, DQ3, DQ5, DQ6). As DR-DQ linkage disequilibrium is well conserved in caucasoid individuals, DQ specificities were inferred from the associated DR specificities. Graft survival rate (%) was significantly lower for the DQ5 D + R - and the DQ6 D - R + combinations when compared with the other corresponding DQ combinations, whereas no significant difference was observed between the DQ2 and DQ3 combinations. In conclusion, if DQ1 plays a prominent role in kidney graft survival, the effects of its splits appear dissociated: DQ5 could be a marker of high antigenicity and DQ6 a marker of high responsiveness.
We recently observed that the prophylactic administration of high doses of OKT3 monoclonal antibody (MoAb) in cadaveric renal transplantation favors the development of thromboses of the grafts' main vessels and of thrombotic microangiopathies. These clinical observations led us to perform sequential determinations of plasma levels of prothrombin fragment 1 and 2 (F 1 + 2) and fibrin degradation products (FDP) after the first injection of 5 or 10 mg OKT3 given as prophylaxis in kidney transplant recipients. The values observed have been compared with those of kidney transplant recipients not treated with OKT3. F 1 + 2 levels peaked four hours after the first injection of 5 mg OKT3 (mean +/- SEM: 4.82 +/- 0.73 vs. 1.75 +/- 0.37 nmol/liter in controls, P < 0.01), indicating activation of the common pathway of the coagulation cascade. FDP levels were already above baseline values at four hours and continued to increase until 24 hours (mean +/- SEM at 24 hr, 4729 +/- 879 vs. 1038 +/- 320 ng/ml in controls, P < 0.05), indicating a fibrinolytic process. The magnitude and the time course of the changes in F 1 + 2 and FDP plasma levels were similar whether the patients received 5 or 10 mg dose of OKT3. The levels of von Willebrand factor (VWF) antigen, a molecule released by activated or damaged endothelial cells, were also significantly increased after injection of OKT3 (mean +/- SEM at 24 hr, 3.67 +/- 0.18 vs. 2.17 +/- 0.11 U/ml in controls, P < 0.05). The procoagulant effects of OKT3 were further investigated in vitro on human umbilical vein endothelial cells (HUVEC).(ABSTRACT TRUNCATED AT 250 WORDS)
We conducted a randomized, prospective study to determine the long-term effects of prophylactic OKT3 in cadaveric renal transplantation. In the first group of patients (n = 56) OKT3 (5 mg/day) was administered for the first 14 postoperative days in association with azathioprine (AZA) and low-dose steroids, cyclosporine (CsA) being introduced on day 11. The other group of patients (n = 52) received CsA from the first POD, together with AZA and steroids. Both protocols were identical from POD 14 on. The total number of infections was higher in OKT3 patients (124/1455 patient-months [P-M] vs. 68/1320 in CsA patients, P less than 0.001) without impact on patient survival (94.5% in OKT3 vs. 93% in CsA patients). OKT3 patients experienced a lower number of rejection episodes (61 per 1455 P-M of risk exposure vs. 81/1320 in CsA patients, P less than 0.05). In addition, the frequency of corticoresistant rejection episodes was lower in OKT3 patients (9 out of 61 vs. 24 out of 81 in CsA patients, P less than 0.05). This resulted in a trend toward improved overall graft survival (83% vs. 75%, P = 0.12) and in a significant increase in immunological graft survival (92% vs. 79%, P = 0.02) in OKT3 patients at 3 years. Taken together, these data suggest that prophylactic OKT3 therapy might have long-term beneficial effects in cadaveric renal transplantation.
Endopeptidase 24.11 (EC 3.4.24.11) enzymatic activity was spectrofluorimetrically measured in human urine, using a synthetic peptidic substrate. Urinary endopeptidase 24.11 output (Uendo) was determined in 24-hour urine samples of 10 kidney transplant recipients during the first 2 weeks after surgery. In 9 patients, a large increase in Uendo levels was noted during the 1st and/or the 2nd postoperative days (mean +/- SEM of peak Uendo 624 +/- 122 micrograms/24 h, p = 0.0003 as compared to 239 +/- 20 micrograms/24 h in a healthy control population). This occurred whether patients received OKT3 (n = 6) or cyclosporine A (n = 3) as primary immunosuppression. Uendo returned to normal between the 3rd and the 5th postoperative day. We conclude that renal transplantation is associated with an early and marked release of endopeptidase 24.11 in urine. This could be due to the potentially toxic effects of ischemia and/or immunosuppressive drugs on the proximal tubular epithelium. The clinical usefulness of urinary endopeptidase 24.11 as a marker of tubular injury remains to be assessed.
In a series of 416 parathyroidectomies for primary or secondary hyperparathyroidism, 19 were reoperations for persistence (17 cases) on recurrence (2 cases) of the disease. (1) Preoperative localisation studies were useless in half of the cases. (2) In re-explorations, 72% only of parathyroid glands were discovered, 46% of them in ectopic locations. In reoperations for primary hyperparathyroidism, 56% of cases had more than one pathological gland. (3) Long term results have been less satisfactory after re-explorations than after the first operations.