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Biomedical subjects

C Nissen

Publications and source records attributed to C Nissen.

At least 145 records · Page 8Linked to original sources
PubMed1983

Cyclosporine in human bone marrow transplantation. Serum concentration, graft-versus-host disease, and nephrotoxicity.

Serum concentrations of cyclosporine were studied in 42 patients given cyclosporine for the prevention of graft-versus-host-disease (GVHD) following allogeneic bone marrow transplantation (BMT). Serum trough levels for cyclosporine were determined in each patient at least once weekly during the first 3 months and were compared with the occurrence of GVHD and with nephrotoxicity. Cyclosporine was given as 20 mg/kg i.m. or as a 24-hr infusion for the first 5-7 days. This was followed by a single daily oral dose of 12.5 mg/kg for 6 months. Cyclosporine was then gradually reduced and stopped after one year. After a median observation period of 2 years 25 of the 42 patients (59%) are alive. Twenty six patients (62%) developed GVHD, which was stage II or more in 11 (26%) and fatal in 2 patients (5%). Five patients developed GVHD 6-8 weeks after withdrawal of cyclosporine one year after BMT. All patients improved after restarting cyclosporine. No correlation between cyclosporine serum concentration and GVHD was observed, but patients with GVHD had greater fluctuations of their serum trough levels. Serum creatinine increased in all patients soon after BMT and was correlated with cyclosporine serum concentration during the first month. Serum creatinine, however, rose further despite lower cyclosporine concentrations in the second month. These results show that cyclosporine effectively reduces the severity, but not the incidence, of GVHD suggesting that there is a subset of cells resistant to cyclosporine. The therapeutic range, however, between high doses (which are often associated with nephrotoxicity) and the minimal effective dose of cyclosporine, has yet to be defined.

Adolescent↗
PubMed1983

Immunologic reactivity in marrow graft recipients receiving cyclosporine to prevent graft-versus-host disease.

In vitro and in vivo immunologic parameters were determined in 26 patients treated continuously with cyclosporine to prevent graft-versus-host-disease (GVHD) after allogeneic bone marrow transplantation (BMT) for acute and chronic leukemia and for aplastic anemia. A group of 18 patients was tested 6 months after BMT and another group of 10 patients was tested after one year. At 6 months after BMT, 94% of the patients had normal serum IgG and IgM levels, whereas at one year 29% of them had low IgA levels. The proportion of patients with normal lymphocyte responses in vitro at 6 months after BMT was 69% and 76% for the responses to concanavalin A and to soluble antigens; 75% and 53% for the responses to allogeneic cells and pokeweed mitogen, respectively; and 89% for the response to phytohemagglutinin. All but one were able to generate suppressor cells upon con A stimulation. At one year after the graft, only one patient had demonstrable multiple abnormalities in in vitro tests. Skin test reactivity at one year was comparable to pre-graft reactivity. After BMT a lymphopenia persisted for 6 months. The rate of infectious complications was high during the first 3 months after BMT, and it diminished progressively as immune functions returned to normal. Infection was the cause of death in two cases (one disseminated cytomegalovirus infection and one septicemia). GHVD occurred in 12 patients; in nine of them the disease was transient and mild, only 1 patient developed severe chronic GVHD. Acute GVHD did not influence the tempo of immunologic reconstitution. In comparison to other studies, it seems that cyclosporine does not delay immune restoration, or increase morbidity from infection, while preventing GVHD and its complications efficiently.

Anemia, Aplastic↗
PubMed1983

Dexamethasone enhances 'CSA' release and depresses 'BPA' release.

Dexamethasone 10(-7) M enhanced the release of granulocyte-macrophage colony stimulating activity (GM-CSA) by peripheral blood cells from 15 normals. In 16 patients with hypoplastic marrow failure this effect was more prominent, the release of GM-CSA being increased up to 10-fold by dexamethasone. Dose-response curves of patient cell supernatants indicate that dexamethasone acts by abrogation of an inhibitor on CSA-production. Dexamethasone decreased the release of burst promoting activity (BPA) in all normals and most patients. We conclude that the interaction of glucocorticoid hormones with lymphocyte function results in positive and negative effects on haemopoiesis in vitro. Preliminary experiments in one patient suggest that the steroid effect in vivo correlates with GM-CSA enhancement in vitro.

Anemia, Aplastic↗
PubMed1983

Haemopoietic stimulators and inhibitors in aplastic anaemia serum.

Normal serum and serum from four patients with severe aplastic anaemia was fractionated by Sephadex G-150 gel filtration. Fractions were tested for direct haemopoietic activity on colony forming cells in methylcellulose cultures, and for their indirect influence on haemopoiesis via CSA- and BPA-producing cells. All aplastic anaemia sera contained abnormal inhibitors and stimulators. An inhibitor acting on both haemopoietic and factor producing cells, eluting with the IgM fraction was found in all, variable inhibitors of lower molecular weight in single patients. Stimulatory activity of 10 000-50 000 MW acting on factor producing cells, but not on colony forming cells directly, was found in all, a variable stimulator eluting with the very high MW fraction in single patients. In two patients who achieved complete autologous bone marrow remission after treatment with high dose immunosuppression, Sephadex fractions of serum before treatment and remission serum were simultaneously tested on autologous bone marrow in remission. Inhibitors were detected before treatment and disappeared in remission, stimulators were not detectable before treatment but became strong in remission. It is concluded that the effect of aplastic anaemia serum on haemopoiesis in culture is determined by the balance of inhibitors and stimulators on both haemopoietic and CSA/BPA producing cells.

Adolescent↗
PubMed1983

Bone marrow graft versus ALG in patients with aplastic anaemia.

Eighty-six successive patients with severe aplastic anaemia were admitted to this hospital between January 1976 and October 1982. They were treated and evaluated in a prospective study according to one protocol. 26 patients with an HLA identical sibling underwent bone marrow transplantation. Overall survival calculated according to Kaplan and Meier in this group is 47%, 60 patients without an HLA identical sibling were given antilymphocyte globulin with or without an infusion of HLA-haploidentical marrow. All these 60 patients received low dose androgens after the procedure. In this study the marrow infusion did not significantly improve the results and overall survival was 74% compared to 70% in patients receiving only antilymphocyte globulin and androgens. In a current pilot study combining ALG and high dose prednisone we were able to further increase remission rates. Between HLA-identical siblings we improved the results of marrow transplants significantly by the use of cyclosporin-A instead of methotrexate for prophylaxis against GvHD.

Adolescent↗
PubMed1982

Allogeneic marrow transplantation for chronic granulocytic leukemia.

Six patients with Philadelphia-chromosome (Ph' +)-positive chronic granulocytic leukemia were transplanted from their HLA-identical siblings after conditioning with cyclophosphamide and 1'000 rad total body irradiation. All received cyclosporin-A for prophylaxis of Graft-versus-Host disease. All patients showed prompt engraftment and all are cytogenetically and clinically in complete remission. Two patients had transient mild signs of Graft-versus-Host-disease and one patient had unilateral facial nerve paresis of unknown origin. All are ambulatory and well 6-18 months (median 10 months) after transplantation.

Adolescent↗
PubMed1982

Differential penetration of DSIP peptides into rat brain.

Delta sleep-inducing peptide (DSIP) or five closely related peptides were injected peripherally and the levels of DSIP-like immunoreactivity measured in the brains of 100 g and 500 g rats decapitated a minute later after washout with 0.9% NaCl. Higher concentrations of immunoreactive material were found in brain tissue with injection of des Trp1-DSIP, D-Ala4-DSIP, and, after correction for cross-reactivity, with D-Ala4-DSIP-NH2 than with the other peptides. Both peptides substituted in the fourth position with D-alanine resulted in higher concentrations in 500 g rats than in 100 g rats, indicating a possible effect of age. The 5-10 fold greater brain to blood ratios of radioactivity after 125I-N-Tyr-DSIP than after 125-I radioiodinated serum albumin (RISA) provided additional evidence against non-specific leakage or contamination of the brains with substantial amounts of residual blood. The results suggest that penetration of the blood-brain barrier (BBB) by small amounts of peptides, at least DSIP peptides, may be somewhat selective.

Animals↗
PubMed1982

Failure of MIF-1 or naloxone to reverse ischemic-induced neurologic deficits in gerbils.

MIF-1 and naloxone exert similar actions in several situations. Since naloxone, at a dose of 1 mg/kg IP, has been reported to reverse the neurologic deficits of gerbils whose right common carotid artery had been occluded, MIF-1 was tested under the same conditions and the effects compared with naloxone. Doses of 0.1, 1.0, and 10.0 mg/kg IP of MIF-1 and naloxone did not significantly alter the signs of either moderate or severe neurologic deficits. Thus, the results of this study with gerbils do not add evidence for the use of these opiate antagonists in strokes.

Animals↗
PubMed1981

[New development in clinical bone marrow transplantation in leukemia].

39 clinical bone marrow transplants (BMT) for leukemia are described. In a historical control series of 18 patients in whom BMT was performed after all chemotherapeutic resources had been exhausted, there is only 1 long-term survivor (5.5%), 8 patients died from GvH reaction, 6 from interstitial pneumonia and 3 from recurrent leukemia. Since 1979 an attempt has been made to transplant patients under optimal conditions (1st complete remission) and cyclosporin-A (CyA) has been used for prophylaxis of GvH reaction instead of MTX. 11 patients were transplanted according to our original proposal (AML and ALL in first remission, CML in chronic phase): 10 have survived without evidence of leukemia (91%), 1 AML died in relapse. 10 patients were grafted in second or later remissions or early relapse: 5 have leukemia-free survival (50%), 1 is living with a relapse. In this group 3 deaths were due to recurrent leukemia and 1 to CMV-infection. In our experience BMT under optimal circumstances does not involve a risk of early mortality and the chances of recurrent leukemia are reduced. Severe or chronic GvH reaction is not seen under CyA. BMT is the treatment of choice for patients with histocompatible sibling donors.

Bone Marrow Transplantation↗
PubMed1981

[Treatment of severe aplastic anemia].

58 patients with severe aplastic anemia (SAA) were treated and evaluated in a prospective study either by bone marrow transplantation (BMT) or by antilymphocyte globulin (ALG). 19 patients were treated with BMT; 9 are still alive 6 months to 5 years after BMT (47%). 39 patients were treated with ALG; 28 are alive 5 months to 5 years after ALG (72%). 24 of these 28 are self-sustaining and in remission. The results show that treatment with ALG is probably superior to treatment with BMT, and also demonstrate that most patients with SAA have a pool of hematopoietic stem cells able to repopulate the marrow after this type of treatment.

Adolescent↗
PubMed1981

Treatment of severe aplastic anaemia with antilymphocyte globulin or bone-marrow transplantation.

Fifty-three patients with severe aplastic anaemia were admitted to this hospital between January 1976 and June 1980, of whom three arrived in terminal condition and died before treatment for their basic disease could be given. Thus 50 patients were treated and evaluated in a prospective study according to one protocol. Eighteen patients with an HLA-identical sibling underwent bone-marrow transplantation with the aim of achieving haematopoietic chimerism. Thirty-two patients without an HLA-identical sibling were given antilymphocyte globulin with or without an infusion of HLA-haplotype-identical marrow. All these 32 patients received low-dose androgens after the procedure. In the first group eight patients (44%) survived. In the two other groups, 22 patients survived (69%), of whom 20 were completely self-sustaining (63%). Engraftment and graft-versus-host disease did not occur in the group who received antilymphocyte globulin and haploidentical marrow, and the haematopoietic reconstitutions in these patients were all autologous. These results confirm the efficacy of antilymphocyte globulin in the treatment of severe aplastic anaemia and show that such treatment is at least as good as bone-marrow transplantation. Its mechanism of action remains unknown, but most patients with aplastic anaemia have a pool of haematopoietic stem cells able to repopulate the marrow after this type of treatment.

Adolescent↗
PubMed1981

Can whole blood be used instead of separated low density cells for examination of the mitogen response?

The response of whole blood and separated low density cells to 3 mitogenic lectins [Phytohaemagglutinin (PHA), Pokeweed mitogen (PWM) and Concanavalin (Con-A)] was tested in 133 normal individual of all ages, including cord blood. The results obtained with the two methods correlated poorly (r = 0.16 for PHA; 0.47 for PWM and 0.42 for Con-A). Thus, the two methods measure different things and results are not comparable.

Blood↗