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Biomedical subjects

D Frei

Publications and source records attributed to D Frei.

At least 19 recordsLinked to original sources

[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

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

[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

[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

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

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

[Acute leukemia after kidney allotransplantation (author's transl)].

Four cases of acute myelogenous leukemia and six cases of chronic myelogenous leukemia after treatment with azathioprine and prednisone for renal allotransplantation have been described in the literature. We report another two cases of acute leukemia 10 and 5 years after successful renal allotransplantation. Patient 1, a 29-year-old farmer, exhibited the signs of acute lymphatic leukemia resistent to treatment with cytostatic agens. Death was due to pneumonia. Patient 2, a 47-year-old salesman, developed pancytopenia together with splenomegaly. After splenectomy an atypical subacute myeloid leukemia became apparent which was not treated due to withdrawal of the patient. He died 2 months after diagnosis. Both patients received long-term immunosuppressive therapy with azathiopine and prednisone until the leukemia was diagnosed. A relationship between long-term immunosuppression and the occurrence of leukemia is postulated.

Adult

[Familial medullary cystic kidney with progressive kidney failure].

The reported case of 2 brothers suffering from medullary sponge kindeys is unique in that uremia developed in spite of the absence of urinary tract obstruction, infection or hypertension. With the exception of congenital nystagmus and psoriasis, none of the extrarenal malformations often associated with medullary sponge kidneys was observed.

Acute Kidney Injury

[Arteriolar hyalinosis in testicular biopsies (author's transl)].

Arteriolar hyalinosis is a common post mortem finding in the testes of even young men. Identical arteriolar hyalinoses can be demonstrated in testicular biopsies of patients with infertility or in patients operated on for cryptorchidism. In a series of such biopsies from 2400 patients, the frequency of arteriolar hyalinosis was examined. In 7 cases with positive findings, histochemical studies were carried out and in an additional 14 biopsies electron microscopy was performed. Arteriolar hyalinosis was found in 3.75% of the 2,400 patients with disturbances of fertility or cryptorchidism. The mean age of these patients was 34 years. In 58% of the cases with arteriolar hyalinosis the basic testicular lesion was tubular atrophy, in 22% cryptorchidism. The arteriolar lesions were due to deposits of lipoids and mucopolysaccharides. Electron microscopy revealed a granular material with vacuoles and rarely myelin bodies below the endothelial layer and between myocytes and fibrocytes of the arteriolar wall. In later stages elastin-like material could be demonstrated in the vicinity of the endothelial cells and collagen fibers at the periphery of these deposits. The etiology of testicular arteriolar hyalinosis and its pathogenetic significance are not yet clear.

Adult