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F Oppenheimer

Publications and source records attributed to F Oppenheimer.

At least 55 records · Page 3Linked to original sources
PubMed2000

Double-blind comparison of two corticosteroid regimens plus mycophenolate mofetil and cyclosporine for prevention of acute renal allograft rejection.

BACKGROUND: Renal transplant recipients experience adverse events attributed to corticosteroid therapy. METHODS: This was a multicenter, randomized, double-blind, 6-month, controlled steroid dose-reduction study in renal transplant recipients with an unblinded 6-month follow-up. In the low/stop arm, corticoste. roids were given at half the dosage of control for 3 months from the date of transplantation, and then withdrawn. Both arms received mycophenolate mofetil and cyclosporine. The primary endpoint was the incidence of biopsy-proven acute rejection at 6 months posttransplantation. RESULTS: There were 248 patients in the control group and 252 in the low/stop group. At 6 months the low/stop group had more biopsy-proven acute rejection episodes than the control (23% vs. 14%; P=0.008). At 12 months this increased to 25% vs. 15%. Most rejections were Banff grade I. Twelve-month graft loss was 5% in the low/stop group vs. 4% in the control. At 6 and 12 months serum cholesterol (P<0.01, P<0.01), triglycer. ides (P<0.01, P<0.01), and systolic blood pressure (P<0.001, P<0.001) were lower in the low/stop group. Diastolic pressure was lower (P<0.01) and lumbar spine bone density was greater (P<0.01) in the low/ stop group at 12 months. CONCLUSIONS: In renal transplant recipients treated with mycophenolate mofetil and cyclosporine, reduction and early withdrawal of the prophylactic corticosteroid dose is feasible without an unacceptable increase in serious rejection episodes. This is accompanied by a significant reduction of steroid-related adverse events.

Adolescent↗
PubMed2000

Pharmacokinetics and pharmacodynamics of mycophenolic acid in stable renal transplant recipients treated with low doses of mycophenolate mofetil.

Suboptimal doses of mycophenolate mofetil (MMF) are frequently employed in renal transplant (Tx) patients, with drug-related side effects or low weight. The aim of this study was to compare the mycophenolic acid (MPA) pharmacokinetic profile and its pharmacodynamic effect on patients receiving either standard (2 g) or low (1.5 g or 1 g) MMF doses, in order to evaluate the therapeutic efficacy of such low doses in inhibiting IMPDH activity. Twenty-seven stable renal Tx recipients aged 18-65 years, with a post-Tx follow-up of 38.5 +/- 44.8 months (6-166 months), receiving 1 g (n = 10), 0.75 g (n = 7) and 0.5 g (n = 10) MMF twice a day in association with cyclosporine and prednisone, were included. The control group was made up of untreated healthy volunteers (n = 5). Plasma concentrations of MPA were analyzed by reverse-phase HPLC. IMPDH activity was determined in lymphocytes by the measurement of 3H release from [2,8-(3)H] hypoxantine. The mean value of areas under the concentration-time curves (AUC(0-12)) of MPA throughout the 12-h dosing interval in patients treated with 2 g was higher than the corresponding data in patients receiving 1.5 g or 1 g bid, but no statistical differences were observed between the three groups. There was no correlation between MPA-AUC(0-12) values and MMF dose (expressed in g/day or g/kg per day). Predose MPA concentrations correlated only weakly with the respective MPA-AUC(0-12) values (r2 from 0.385 to 0.655), whereas an acceptable correlation was observed between MPA Cmax and MPA-AUC(0-12) (r2 from 0.626 to 0.759) in 2 g, 1.5 g, and 1 g MMF groups. An inverse relationship between MPA concentrations and IMPDH activity was observed. In general, the maximum MPA concentration was achieved from 1 h to 2 h after dosing, and the maximum inhibition of IMPDH was also from 1 h to 2 h after dosing. The evaluation of IMPDH activity demonstrated that there was a significant statistical difference between samples from 0 to 1 h (P = 0.008) and 0 to 2 h (P = 0.04). In conclusion, concentration-time profiles of renal transplant recipients administered 0.75 g and 0.5 g twice a day are slightly lower than those from the 2 g group, but nor significantly. On the other hand, inhibition of IMPDH activity was comparable in the three groups, indicating considerable interindividual pharmacodynamic variability. Pharmacodynamic monitoring of the degree of immunosuppression and its correlation with MPA plasma concentrations will be assessed further in future studies.

Adolescent↗
PubMed2000

Normothermic recirculation reduces primary graft dysfunction of kidneys obtained from non-heart-beating donors.

Our aim was to analyze the short- and long-term function of kidneys procured from non- heartbeating donors (NHBD) by means of three techniques: in situ perfusion (ISP), total body cooling (TBC) and normothermic recirculation (NR). Fifty-seven potential NHBD were included. Mean warm ischemia time was 68.9 +/- 35.6 min. Forty-four kidneys were obtained from donors perfused with ISP, 8 with TBC, and 8 with NR. Eighteen kidneys (32%) started functioning immediately, 29 (52%) showed delayed graft function (DGF) and 9 (16%) showed primary non function (PNF). The actuarial graft survival rate was 76.4% at 1 year and 56% at 5 years. The patient survival rate was 89.3% at 5 years. Incidence of DGF and PNF was significantly lower in kidneys perfused with NR than those with ISP or TBC (P < 0.01). Duration of DGF was shorter in kidneys obtained through TBC than in kidneys obtained with ISP (P < 0.05). In conclusion, NR reduces the incidence of DGF and may be considered the method of choice for kidney procurement from NHBD.

Adult↗
PubMed2000

Indium-111 labelled platelet scintigraphy can predict the immunological origin of fever in patients on dialysis carrying a non-functioning renal allograft.

The purpose of this study was to evaluate the usefulness of labelled platelet scintigraphy in the differential diagnosis of a prolonged febrile syndrome (PFS) in patients on dialysis carrying a non-functioning renal allograft. We prospectively performed an indium-111 mercaptopyridine-labelled platelet scan on 91 patients (54 men, 37 women; mean age 39.6+/-12 years). The mean duration of PFS was 35 days (range 7-122). Forty-six of the 91 patients underwent steroid therapy (2-10 mg/day). Platelet labelling was carried out following Thakur's method. Platelet scans were performed 48 h after reinjection of labelled platelets. The platelet uptake index (PUI) was calculated by dividing the cpm/pixel in the allograft ROI by cpm/pixel in a mirror background ROI. The final diagnosis of PFS was established depending on the outcome after treatment. In 61/91 patients the fever had an immunological origin because it disappeared after graft embolisation or transplantectomy. In 30/91 patients the PFS disappeared after antibiotic therapy (non-immunological origin). The PUI in patients with immunological PFS was 1.80+/-0.7, while in patients with non-immunological PFS it was 1.12+/-0.1 (P<0.05). When a PUI of > or =1.5 was considered as the threshold to establish PFS of immunological origin, the sensitivity of platelet scan was 76%, the specificity 100%, and the negative and positive predictive values 69% and 100%, respectively. In patients classified with immunological PFS who underwent steroid therapy, the PUI was significantly lower than in patients without steroids (P<0.05). These results suggest that 111In-labelled platelet scintigraphy can accurately predict an immunological PFS in patients on dialysis carrying a non-functioning renal allograft. Therapy with steroids could reduce the sensitivity of 111In-labelled platelet scintigraphy in detecting immunological PFS.

Abdomen↗
PubMed2000

Compression of the ulnar nerve in Guyon's canal by uremic tumoral calcinosis.

We describe the case of a 70-year-old woman with chronic renal failure on haemodialysis presenting with an ulnar nerve compression in Guyon's canal secondary to uremic tumoral calcinosis. Excision of calcium deposits and external neurolysis of the ulnar nerve were successfully performed. Simultaneously, the hyperphosphatemia and hypercalcemia were corrected. The pathogenesis of this condition is different from primary tumoral calcinosis. Clinical and radiological features and therapy are discussed. Uremic tumoral calcinosis is an unusual etiology of ulnar nerve compression in Guyon's canal not previously reported in dialysis patients.

Aged↗
PubMed2000

Increased prevalence of polycystic kidney disease type 2 among elderly polycystic patients.

Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous, with at least three chromosomal loci (PKD1, PKD2, and PKD3) accounting for the disease. Mutations in the PKD2 gene, on the long arm of chromosome 4, are estimated to be responsible for 15% of the cases of ADPKD, based on linkage studies. PKD2 is a milder form of the disease, with a mean age of end-stage renal disease (ESRD) approximately 20 years later than PKD1. The object of this study is to determine the proportion of elderly patients with ADPKD with ESRD who harbor mutations in the PKD2 gene. We analyzed all exons and intron-exon boundaries of the PKD2 gene by single-strand conformation polymorphism analysis and silver staining technique in 46 patients with ADPKD who reached ESRD after the age of 63 years or were not yet undergoing renal replacement therapy (RRT) by that age. We performed exactly the same studies in a control group of 40 patients with ADPKD with unknown gene status aged younger than 63 years. In 22 patients, a mutation in the PKD2 gene was defined: 18 of 46 patients from the elderly group and 4 of 40 patients from the control group. We identified 14 different mutations: 4 nonsense mutations, 1 missense mutation, 5 small deletions, 2 insertions, 1 deletion of the whole PKD2 gene, and 1 splicing mutation. Five of these mutations previously were described by our group. Three of the mutations reported in the present study are recurrent. The prevalence of PKD2 disease among elderly patients with ADPKD undergoing RRT is 39.1%, almost three times the prevalence of the disease in the general ADPKD population.

Adult↗
PubMed2000

Assessment of mycophenolic acid-induced immunosuppression: a new approach.

BACKGROUND: Mycophenolic acid (MPA), a metabolite of mycophenolate mofetil (MMF), is an immunosuppressive agent that inhibits inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the ex novo synthesis of GTP. We measured IMPDH activity in peripheral blood mononuclear cells (PBMCs) from MMF-treated patients to evaluate the efficacy of MMF in individual patients. METHODS: IMPDH activity was measured by (3)H released from [2,8-(3)H]IMP that had been formed in the cells from added [2,8-(3)H]hypoxanthine in PBMCs of 35 renal transplant recipients treated with cyclosporin A and corticoids plus MMF: 2 g (n = 10), 1.5 g (n = 7), 1 g (n = 10), or 0 g (n = 8) per day. An alternative method, based on the capacity of the patients' sera to inhibit spontaneous proliferation of the CEM cell line, was also analyzed. RESULTS: The IMPDH activity of PBMCs in transplanted patients was highly variable. For the method based on CEM cell line proliferation: (a) cell proliferation was inhibited only in MMF-treated patients; (b) there was a clear postdose increase in inhibition; (c) inhibition was not affected by other immunosuppressants in vitro or in vivo; (d) inhibition from predose to predose sample was correlated; and (e) when the MMF dosage was <20 mg. kg(-1). day(-1), two groups of patients were identified, one that maintained a high inhibitory capacity in all dose intervals, and one with periods of low inhibitory capacity. CONCLUSIONS: Measurement of the inhibition of CEM cell line proliferation by sera from MMF-treated patients may be useful for evaluating the relative efficacy of MMF treatment in individual patients, especially those receiving low doses of MMF.

Adult↗