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Biomedical subjects

J L Vanherweghem

Publications and source records attributed to J L Vanherweghem.

At least 55 records · Page 3Linked to original sources

Insulin-like growth factor I values in patients on maintenance hemodialysis: relationship to growth hormone and albumin levels.

Twenty-seven uremic patients (blood urea: 58.2 +/- 2.2 mmol/l; blood creatinine: 1,069 +/- 53 mumol/l; mean +/- SE) on maintenance dialysis were investigated immediately before and after a dialysis session. Control data were obtained from 30 normal volunteers. Before dialysis, circulating levels of insulin-like growth factor I (IGF-I) were similar in anuric and nonanuric patients, averaging 305 +/- 24 micrograms/l, a value not different from that observed in normal controls (262 +/- 16 micrograms/l). IGF-I levels were not modified by dialysis. In contrast, GH values were significantly higher in uremic patients (3.6 +/- 0.6 microgram/l) than in normal controls (2.5 +/- 0.5 microgram/l) and decreased significantly after the dialysis session (0.8 +/- 0.1 microgram/l). IGF-I values were positively correlated with GH and albumin, but not with the various parameters of renal insufficiency, suggesting that in chronic renal failure, synthesis of IGF-I appears to be regulated, as in normal subjects, by growth hormone and nutritional status.

Adult↗

Twenty-four-hour blood pressure and heart rate patterns in chronic hemodialysis patients.

To test the assumption that the previously reported abnormal 24-hour blood pressure (BP) variations in hemodialysis (HD) patients might be due to associated complications of chronic renal failure, we recorded the 24-hour noninvasive BP and heart rate (HR) patterns in 14 carefully selected chronic HD patients. No of the patients suffered from orthostatic hypotension, and all were free of any previously reported associated condition known to affect the 24-hour BP profiles. The BP and HR profiles were quantitatively analyzed using the periodogram method. The results were compared those from 14 controls matched for age, sex, and casual BP. No difference could be found between the HD patients and the controls, either in the absolute and relative amplitudes of the 24-hour systolic BP and diastolic BP variations or in the timings and levels of their respective acrophases and nadirs (except for the timings of the second systolic BP and diastolic BP acrophases; P < 0.05). The absolute levels of the HR acrophases and nadirs were higher in the HD patients than in the controls (P < 0.05 and P < 0.01, respectively), while both the absolute and relative amplitudes of the 24-hour HR profiles and the relative values and timings of the HR acrophases and nadirs were similar in both groups. Consequently, the 24-hour HR pattern was similar in the HD patients than in the controls, except that the entire profile was shifted upward.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Adhesion molecules and leukocyte common antigen on monocytes and granulocytes during hemodialysis.

As contact of blood with artificial membranes may activate cell adhesiveness, we investigated in 5 patients the expression of several adhesion-promoting molecules on monocytes and granulocytes during hemodialysis on cuprophane (CU), cellulose acetate (CA), and polyacrylonitrile (PAN) membranes. After staining with specific fluorescent monoclonal antibodies, flow cytometric analysis was performed to evaluate the expression of CD11b (= Mac 1, CR3, or C3bi receptor), CD11a (= leukocyte function antigen 1 or LFA-1, or gp 180/95), CD54 (= intercellular adhesion molecule 1 or ICAM 1), and CD45 (= leukocyte common antigen) on circulating leukocytes. Granulocytopenia occurred at 15 minutes with CU and CA but not with PAN; significant monocytopenia occurred on the contrary with all 3 membranes. The drop in monocyte counts was maximal at 15 minutes on CU and CA, and at 180 minutes on PAN; it was also more important with CU (88 +/- 2.6%, alpha = 0.005) and CA (66.4 +/- 4.1%, alpha = 0.01) than with PAN (36.2 +/- 6.2%). Hemodialysis on CU, CA, and PAN was associated with a 2- to 3-fold CD11b and CD45 overexpression on peripheral monocytes; these molecules also increased on circulating granulocytes but to a lesser extent on PAN than on CU and CA (alpha < 0.05). There were no hemodialysis-induced changes in CD11a and CD54 expression on circulating monocytes or granulocytes. The upregulation of CD11b may provide a molecular mechanism for the sequestration of monocytes and granulocytes in the circulation during hemodialysis, while upregulation of CD45 might reflect mechanisms regulating the leukocyte activation state.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗

Induction of thromboses within renal grafts by high-dose prophylactic OKT3.

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.

Humans↗

High or low dose steroid therapy for acute renal transplant rejection after prophylactic OKT3 treatment: a prospective randomized study.

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.

Acute Disease↗

Procoagulant effect of the OKT3 monoclonal antibody: involvement of tumor necrosis factor.

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)

Adult↗

The long-term effects of prophylactic OKT3 monoclonal antibody in cadaver kidney transplantation--a single-center, prospective, randomized study.

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.

Adult↗

Pathological release of urinary endopeptidase 24.11 early after 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.

Biomarkers↗

Effect of recombinant human erythropoietin therapy on ambulatory blood pressure and heart rate in chronic haemodialysis patients.

Systemic hypertension as assessed by causal blood pressure measurements is a frequently reported side-effect of recombinant human erythropoietin (rHuEpo) treatment. We investigated the effect of rHuEpo treatment on the 24-h ambulatory blood pressure and heart rate profiles of 13 chronic haemodialysis patients. After 3-4 months of rHuEpo therapy it was found that the mean haematocrit had increased from 24.5 +/- 1.0% to 32.0 +/- 1.1% (P less than 0.005), while body-weight and control of uraemia as assessed by routine laboratory data remained unchanged. Despite gradual and incomplete correction of anaemia by use of low doses of rHuEpo, increases in the ambulatory systolic and diastolic blood pressure were found. The greatest increases affected day-time systolic blood pressure and night-time diastolic blood pressure, and these increases were significant (P less than 0.05). As a result, pulse pressure increased during day-time (P less than 0.05) while the night-time decline in diastolic blood pressure disappeared. An increase in peripheral resistance after partial correction of renal anaemia might explain these observations. rHuEpo therapy increased the percentage of abnormal ambulatory blood pressure measurements (defined as systolic blood pressure greater than 140 mmHg and/or diastolic blood pressure greater than 90 mmHg) from 33% to 52% (P less than 0.05) while in contrast, mean casual prehaemodialytic and posthaemodialytic blood pressure values remained unchanged. We conclude that changes in 24-h blood pressure profiles should be carefully assessed by ambulatory blood pressure monitoring in haemodialysis patients treated with rHuEpo, since these changes are likely to be missed when only causal blood pressures are measured.

Anemia↗

Anaphylactoid reactions during hemodialysis on AN69 membranes in patients receiving ACE inhibitors.

We report five life-threatening anaphylactoid reactions occurring within the very first minutes of hemodialysis on polyacrylonitrile (AN69) capillary dialyzers in three patients receiving ACE inhibitors. Such reactions were not observed either in patients treated with ACE inhibitors but dialyzed on other membranes (N = 9), nor in patients on AN69 who did not receive ACE inhibitors (N = 19). These anaphylactoid reactions could be due to bradykinin accumulation, as a result of both increased synthesis--by interaction of blood with the AN69 polymer--and catabolism blockade by ACE inhibitors.

Acrylic Resins↗

Intraperitoneal secretion of interleukin-6 during continuous ambulatory peritoneal dialysis.

Interleukin-6 (IL-6) was determined in serum and peritoneal dialysis effluent (PDE) of patients on chronic ambulatory peritoneal dialysis (CAPD) by a biological assay measuring the proliferation of the IL-6-dependent 7TD1 cell line. Six patients free of peritonitis displayed low but significant levels of IL-6 (mean +/- 42 pg/ml) in PDE, while IL-6 was undetectable in serum. In 6 patients with staphylococcal peritonitis, a tremendous increase in PDE levels of IL-6 was noted (range: 5,832-37,491 pg/ml), while serum IL-6 remained either undetectable or on a low level except in one case. After 5 days of antibiotic treatment, IL-6 levels in PDE returned to basal values. We conclude that CAPD results in an intraperitoneal secretion of IL-6 which is markedly but transiently increased during peritonitis episodes.

Ascitic Fluid↗