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Biomedical subjects

D Frei

Publications and source records attributed to D Frei.

At least 19 recordsLinked to original sources
PubMed1999

Integrated analysis of thrombotic/vascular event occurrence in epoetin alfa-treated patients undergoing major, elective orthopedic surgery.

Data from four prospective, multicenter, randomized studies involving 869 major, elective orthopedic surgery patients were examined by means of a retrospective integrated analysis to evaluate whether perioperative Epoetin alfa use was associated with the occurrence of thrombotic/vascular events. The incidence of thrombotic/vascular events was similar between 619 patients treated with Epoetin alfa and 250 patients receiving placebo (7.4% versus 8.0%, respectively). Regression analyses identified age, cardiac history, hypertension, and cardiac medications, but not Epoetin alfa, as risk factors for thrombotic/vascular events. The analysis did not implicate an increase in the rate of rise in hematocrit or maximum hematocrit obtained prior to surgery as contributors to thrombotic events. Thus, Epoetin alfa, which enhances preoperative erythropoiesis and increases hematocrit, did not affect the probability of thrombotic/vascular events.

Epoetin Alfa↗
PubMed1999

The predictive power of baseline hemoglobin for transfusion risk in surgery patients.

Preoperative hemoglobin concentration may be an important predictor of transfusion risk in surgical procedures with significant expected blood loss. Contemporary studies investigating transfusion risk with regard to the relationship between perioperative administration of Epoetin alfa and baseline hemoglobin provide data to test this hypothesis. The predictive power of seven preoperative variables (hemoglobin concentration, age, erythropoietin level, ferritin concentration, serum iron, total iron-binding capacity, and predicted blood volume) on transfusion risk was examined via retrospective logistic regression analysis of 276 orthopedic surgical patients. In the two studies used to perform the regression analysis, patients were treated daily with either Epoetin alfa or placebo. Based on the retrospective analyses, a prospective study was conducted to validate the hypothesis. Of the seven variables evaluated, baseline hemoglobin concentration and predicted blood volume were significantly predictive of transfusion risk in both Epoetin alfa- and placebo-treated patients. Further, an inverse correlation between hemoglobin concentration and transfusion risk was demonstrated in placebo-treated patients. Placebo-treated patients with hemoglobin > 10 to < or = 13 g/dL had an approximately twofold greater risk of transfusion than patients with hemoglobin > 13 g/dL. In contrast to placebo treatment, Epoetin alfa significantly reduced transfusion risk in patients with hemoglobin > 10 to < or = 13 g/dL. Baseline hemoglobin concentration is an excellent predictor of transfusion risk in orthopedic surgical patients. As a result, hemoglobin testing should be considered a part of routine preoperative testing for orthopedic surgical patients.

Arthroplasty, Replacement, Hip↗
PubMed1996

Baseline hemoglobin as a predictor of risk of transfusion and response to Epoetin alfa in orthopedic surgery patients.

A multicenter, double-blind, placebo-controlled, parallel-group study was undertaken to determine whether Epoetin alfa can reduce perioperative transfusion requirements. Twenty-six medical centers enrolled 316 patients who were scheduled for major orthopedic surgery and were expected to require > or = 2 units of blood. Patients were stratified according to baseline hemoglobin levels and randomly assigned to receive either Epoetin alfa (300 IU/kg or 100 IU/kg) or placebo for 15 consecutive days starting 10 days prior to, on the day of, and for 4 days after surgery. Epoetin alfa (300 IU/kg) resulted in significantly less exposure to allogeneic blood transfusion compared with placebo (16%) versus 45%) in patients whose baseline hemoglobin level was > 10 to < or = 13 g/dL (P = 0.024). Mean number of units transfused per patient was also lower among those treated with Epoetin alfa (overall, P = 0.027). Epoetin alfa was safe and well tolerated in this population.

Aged↗
PubMed1996

A safety and efficacy comparison study of two dosing regimens of epoetin alfa in patients undergoing major orthopedic surgery.

Previous studies have demonstrated the efficacy of perioperative Epoetin alfa in decreasing allogeneic transfusion exposure in patients undergoing orthopedic surgery. A randomized, multicenter trial was conducted comparing the safety and efficacy of a weekly Epoetin alfa dosing regimen in patients with hemoglobin levels > or = 10 to < or = 13 g/dL scheduled to undergo major elective orthopedic arthroplasty, with a daily regimen previously shown to be effective. patients on the weekly regimen showed a greater baseline-to-presurgery hemoglobin increase versus the daily regimen group (1.44 +/- 1.029 g/dL versus 0.73 +/- 0.867 g/dL). Moreover, the weekly 600 IU/kg regimen was similar to the daily 300 IU/kg regimen with respect to safety and the avoidance of allogeneic transfusion. These data showed the weekly Epoetin alfa regimen to be at least as efficacious as the daily regimen and more convenient.

Aged↗
PubMed1990

[The effect of rejection crises and immunosuppressive therapy on the lymphocyte subpopulations of patients after kidney transplantation].

The lymphocyte subsets in the peripheral blood were examined 3 times a week in 17 patients receiving a cadaveric renal allograft using 2-color flow cytometry and several combinations of monoclonal antibodies. Patients who experienced a rejection crisis (n = 12) had a significantly higher CD4/CD8-ratio (2.72 +/- 1.26 mean +/- SD) than patients with stable graft function (1.76 +/- 1.33, p less than 0.05). 9/12 patients showed 0-3 days prior to the rejection episode an increase of the CD4/CD8- ratio (greater than or equal to 0.5) and/or a high ratio (greater than or equal to 2.5) with a decrease following antirejection therapy. The activation markers HLA-DR and IL-2 receptor on T cells were increased only during 3/12 rejection episodes. Patients with rejections resistant to prednisone pulse therapy (n = 6) had significantly more lymphocytes/mm3 in the peripheral blood (1111.7 +/- 597.5) than successfully treated patients (n = 6, 336.7 +/- 196.0, p less than 0.02). Antirejection therapy with prednisone pulses and/or antithymocyte globuline resulted in a significant decrease of T lymphocytes (CD3+) with a selective reduction of T helper/inducer cells (CD4+). 6 months after renal transplantation the patients had a higher percentage of suppressor/cytotoxic cells (CD8+) compared to the pretransplant values (26.3 +/- 10.9% vs 17.7 +/- 6.2%, p less than 0.02) and blood donors (16.3 +/- 6.2%, p less than 0.01). Furthermore the percentage of T helper cells (CD4+/CD28-) was significantly higher and the T suppressor-inducer cells (CD4+/CD28+) were significantly lower compared to the controls. Serial flow cytometric determinations of lymphocyte subsets in renal allograft recipients may be helpful in some cases although rejection episodes could not be predicted in the individual patient.

Adult↗
PubMed1990

Post-transplant diabetes mellitus in renal allograft recipients: a matched-pair control study.

The incidence of post-transplant diabetes mellitus was evaluated retrospectively in 901 consecutive renal transplant recipients. Thirty-two (3.6%) patients developed diabetes mellitus requiring drug therapy. 18 of 32 became hyperglycaemic within 3 months of transplantation. Post-transplant diabetes mellitus occurred in 24 of 628 (3.8%) patients treated with conventional therapy consisting in azathioprine and prednisone, and in 8 of 273 (2.9%) patients receiving cyclosporin A (CsA) in addition (triple therapy). To identify predisposing factors 32 non-diabetic patients matched for age, sex, number of graft, immunosuppressive protocol, and graft function at onset of diabetes were used as case controls. Thirteen of 32 patients with diabetes mellitus and 5 of 32 control patients had abnormal glucose tolerance pretransplant (P less than 0.025). HLA-B8 was significantly more frequent in patients with post-transplant diabetes mellitus than in control patients (9 of 29 vs 2 of 31, P less than 0.02). Twelve (38%) patients became diabetic during or immediately after anti-rejection therapy with intravenous pulse prednisone. Four diabetic patients experienced chronic pancreatitis pre-transplant. Family history of diabetes mellitus, bodyweight, number of rejection episodes, and immunosuppressive drug doses were similar in both groups. Actuarial patient and graft survival was not significantly different in diabetic patients and controls, although 10-year data tended to be better in controls. Thus, post-transplant diabetes mellitus was not a frequent complication in patients sometimes predisposed by an impaired glucose tolerance pre-transplant and was triggered by pulse prednisone therapy in 38%.

Adult↗
PubMed1989

[Erythropoiesis and serum erythropoietin concentrations before and after kidney allotransplantation].

Hematological parameters and serum erythropoietin (EPO) levels were measured before and sequentially after grafting in 50 consecutive cadaver renal transplant recipients. EPO was estimated using a sensitive radioimmunoassay. Values for nonanemic controls were 15-25 mU/ml. Mean hematological values before transplantation were as follows: hemoglobin 9.7 +/- 2.4 g/dl; hematocrit 29 +/- 8%; corrected reticulocytes count 15 +/- 8% and EPO 29 +/- 23 (11-131) mU/ml. In the entire studied population, 35 patients had inadequate low EPO levels for their degree of anemia. In the whole population, there was a significant positive exponential correlation between EPO and hematocrit (r = 0.31; p less than 0.05). In the subset of patients with underlying cystic kidney disease and in hemodialysis patients treated with recombinant human EPO, hemoglobin, hematocrit and EPO levels were higher when compared to hemodialysis or CAPD patients with other kidney diseases. Following successful renal transplantation, EPO increased to 45 +/- 31 mU/ml at 1 month and then decreased to 25 +/- 18, 18 +/- 7 and 19 +/- 4 mU/ml at 3,6 and 9 months, respectively. Within the 1st month after transplantation there was a 4-fold increase in reticulocytes from 9 +/- 5 to 38 +/- 14%, followed by a slow decrease over the next several months to 23 +/- 11% at 9 months. In contrast, the hematocrit level rose more gradually from 28 +/- 7 to 44 +/- 6% at 9 months. In 25 of 36 patients with a functioning graft who were followed for more than 6 months, anemia was corrected and 11 patients remained slightly anemic with a mean hematocrit level of 36 +/- 4%.

Erythropoiesis↗
PubMed1988

[Kaposi's sarcoma following kidney transplantation: remission following reduction of immunosuppression and consequent HIV infection].

Kaposi's sarcoma (KS) in renal allograft recipients is a rare though serious complication of immunosuppressive treatment. Therapeutic procedures such as surgical excision and local irradiation are inappropriate, since the endothelial-originated tumor is often multicentric. However, systemic treatment such as chemotherapy entails further immunosuppression. We observed a patient with renal allograft who developed disseminated KS of legs and trunk while receiving azathioprine, cyclosporin and prednisone after intensive rejection therapy with high dose corticosteroids, antithymocyte globulin and transplant irradiation. At that time the immunological status was similar to that of an AIDS patient, though HIV serology was negative. Azathioprine was withdrawn while cyclosporin and prednisone were continued. KS disappeared shortly after without a decrease in allograft function, and immunological parameters tended to normalize. When KS had disappeared almost completely the patient became infected with HIV. Complete remission was not hampered, nor was there recurrence of KS. The late appearance of HIV-antigenemia with seroconversion in the course of the tumor makes HIV unlikely as a causative factor. The predisposing factors for KS after renal transplantation are discussed: 1. Amplification of immunosuppression due to rejection therapy, 2. Genetic predisposition such as HLA DR5 antigen, 3. Cytomegalovirus infections. For therapy of iatrogenic KS we propose reduction of immunosuppressive therapy before additional chemotherapy is initiated.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Two independent receptors allow selective target lysis by T cell clones.

Dimethylbenzanthracene-induced P1 sarcoma cells induce P1-specific antibodies in syngeneic DA rats. Antiidiotypic antibodies of specificity DA anti-(DA anti-P1) were induced against the tumor-specific antibodies and used to restimulate P1-primed DA T cells in vitro. Using antiidiotypic antibodies and T cell growth factor, P1-specific cytotoxic DA T cell clones were established by limiting dilution and kept in vitro. Two of these clones acquired during culture periods in addition to the P1 specificity lytic activity towards natural killer (NK) targets YAC-1 or K562. Cold target inhibition experiments showed that the very same cytotoxic T cells kill P1 and NK targets. Antiidiotypic antibodies of specificity DA anti-(DA anti-P1) inhibited cytotoxicity against P1 but not against YAC-1 or K562. We conclude that two independent receptors are located on these double-reactive T cell clones, one that is idiotypic and antigen-specific, and another displaying the binding profile of NK cells.

Animals↗
PubMed1982

A matched-pair control study of postrenal transplant polycythemia.

Polycythemia developed in 18 of 133 first kidney allograft recipients (13.5%) with onset from the third month to the fifth year posttransplantation. A group of matched nonpolycythemic patients were used as case controls to compare multiple variables in order to identify predisposing factors. In the polycythemia group, there were: (1) significantly more patients who had not undergone pretransplant nephrectomy; (2) significantly more patients who had glomerulonephritis as original disease; (3) significantly more patients who had received pretransplant transfusions; and (4) significantly more patients who were hypertensive posttransplant. Thus, the factors of the presence of native kidneys, original disease, pretransplant transfusions as well as hypertension posttransplant are factors associated with the presence of posttransplant polycythemia. This condition is usually self-limiting and benign.

Adolescent↗