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Biomedical subjects

C Nissen

Publications and source records attributed to C Nissen.

At least 127 records · Page 7Linked to original sources
PubMed1986

Treatment of severe aplastic anemia.

A total of 100 patients with severe aplastic anemia were treated and evaluated in a prospective study at our hospital between January 1976 and October 1983: 28 patients had an HLA-identical sibling donor and were treated with bone marrow transplantation, and 72 patients without an HLA-identical sibling donor were given antilymphocyte globulin followed by oral low-dose androgen therapy. At 1 1/2-9 years after treatment, 13 patients (46%) survive in the transplant group and 45 patients (75%) survive in the second group. All except one in the second group have self-sustaining hematopoiesis without need for transfusions. There is one major difference between the two therapies. Marrow transplantation restores bone marrow function completely and no late hematologic complications have been seen in this group. The majority of patients treated with antilymphocyte globulin in contrast have residual abnormalities of hematopoiesis: macrocytosis, mild granulocytopenia, and mild thrombopenia. Relapse (11 of 72 patients) and clonal hematologic disorders, such as paroxysmal nocturnal hemoglobinuria (four patients) and leukemia (one patient) can occur years after complete bone marrow reconstitution with antilymphocyte globulin. These late disorders are of concern. Despite this, we conclude that antilymphocyte globulin treatment is an effective therapy with low early mortality and morbidity and a high chance for a long, sustained remission. Results are better or at least equivalent to bone marrow transplantation and patients with donors should be given the option of transplant or antilymphocyte globulin.

Adolescent↗
PubMed1985

[Incidence, characteristics and clinical importance of autolymphocytotoxins in aplastic anemias].

Sixteen (24%) of 68 patients with aplastic anemia had antibodies cytotoxic to their own lymphocytes before specific disease treatment. These antibodies displayed the characteristics of cold reactive lymphocytotoxins (LTs). No correlation existed between the detection of auto-LTs and a viral or toxic cause of the disease or the patients' HLA genotype. A lower frequency of anti-HLA antibodies was recorded in the pretreatment sera of patients with auto-LTs. However, the response rate to antilymphocyte serum treatment and the outcome of the bone marrow grafts were comparable among the patient's groups with or without pretreatment auto-LTs.

Adolescent↗
PubMed1985

[Invasive pulmonary aspergillosis--a diagnostic and therapeutic problem in patients with severe aplastic anemia].

Three young patients with severe aplastic anemia undergoing intensive immunosuppressive therapy developed fever and pulmonary infiltrates during longlasting severe granulocytopenia, despite multiple broad spectrum antibiotic combinations and granulocyte transfusions. Invasive pulmonary aspergillosis was diagnosed only by thoracotomy. In conjunction with high dose amphotericin-B therapy complete resolution of aspergillosis was achieved in two cases, paralleled by slow recovery of bone marrow function, whereas in the third case only a partial remission was possible together with transient amelioration of granulopoiesis. We suggest early aggressive surgical methods to establish the diagnosis of aspergillosis in these severely menaced patients, so that antifungal therapy with high dose amphotericin-B can be initiated at an early stage.

Adolescent↗
PubMed1985

Unidirectional influx and phosphorylation of glucose analogues in cultured astroblasts.

Unidirectional influx of 14C-3OMG (3-O-methyl-D-glucose) and rate of phosphorylation of 14C-2DG (2-deoxy-D-glucose) were determined in primary cultures of astroblasts under conditions with negligible unstirred layers. The influx exhibited rate constants between 7.2 and 8.3 min-1 in the concentration range 2.5-25 mM of unlabeled 3OMG and was considered constant, irrespective of concentration of 3OMG. The rate of phosphorylation of 14C-2DG declined for rising concentrations of 2DG and hence showed saturability. The rate constants ranged from 7.9 to 0.1 min-1 in the concentration range 0.04-25 mM of 2DG. These results are not consistent with the view that the influx limits the rate of phosphorylation. They support the notion that the influx is not rate limiting for the phosphorylation.

3-O-Methylglucose↗
PubMed1985

Stimulatory serum factors in aplastic anaemia. I. Serum 'releaser' activity for haemopoietic growth factors, a regulator?

Human serum contains an activity which enhances the release of colony stimulating and burst promoting activity (CSA and BPA). It is low in the majority of normal sera and was found elevated in patients with aplastic anaemia. The patient's 'response' to autologous serum releaser activity was measured by comparing CSA and BPA release by patient cells in percentage of release by normal cells. This 'response' was negatively correlated with serum releaser activity (P = 0.0035 for CSA-release, P less than 0.0001 for BPA-release), i.e. releaser activity was high, when factor release was low. This inverse relationship between releaser activity and the patient's response was also observed in four patients with pancytopenia of causes other than aplastic anaemia. We conclude that elevated serum releaser activity reflects a repair mechanisms which operates when CSA- and BPA-production is inadequate. Thus, releaser activity is likely to be a haemopoietic regulator.

Anemia, Aplastic↗
PubMed1985

Stimulatory serum factors in aplastic anaemia. II. Prognostic significance for patients treated with high dose immunosuppression.

Serum from patients with aplastic anaemia contains two distinct stimulatory activities on haemopoiesis in culture. The first is a highly unstable enhancing activity, which mainly stimulates colony formation from BFU-E and macrophage precursors, and only acts when added directly to target bone marrow cultures. It is destroyed by Sephadex G-150 chromatography, and thus differs from colony stimulating activity (CSA) and burst promoting activity (BPA). Its mode of action is unknown. It was elevated in 70/97 patients with severe aplastic anaemia (SAA). 71 of these 97 patients were treated with high dose immunosuppression. 55/71 who achieved self-sustaining haemopoiesis had higher serum stimulating activity on BFU-E than 16/71 who never achieved remission (P = 0.0004). It was predictive of response as an all or none phenomenon, independent of the time required for recovery. It was, however, unsatisfactory as a single prognostic test. Bone marrow reconstitution also occurred in 4/71 patients whose serum inhibited BFU-E in direct culture. The second stimulator acts via enhancement of CSA- and BPA-release by accessory cells and is therefore termed 'releaser' activity. It was elevated in 27 of 51 aplastic anaemia patients and did not correlate with direct stimulatory activity. High 'releaser' activity was not predictive of response in 42 patients treated with high dose immunosuppression. However, the ability of patient cells to respond to autologous 'releaser' activity was a positive risk factor. Patients whose cells released an excess of CSA in the presence of autologous serum had a significantly higher chance of autologous recovery within 3 months than patients who produced little or no CSA in the presence of normal or excess releaser activity (P less than 0.0001). A scoring system which includes these two good risk factors is proposed for estimation of a patient's probability to recover autologous bone marrow reconstitution.

Anemia, Aplastic↗
PubMed1985

The effect of cytomegalovirus infection on T lymphocytes after allogeneic bone marrow transplantation.

The influence of cytomegalovirus (CMV) infection on peripheral T lymphocyte repopulation was studied in 59 bone marrow transplant (BMT) recipients who received either cyclosporin A (CyA) or methotrexate (MTX) as prophylaxis for acute graft-versus-host disease. We used monoclonal antibodies and single- or double-marker immunofluorescence for the quantitation of T4+, T8+ and HNK1+ T cell subpopulations. CMV infection was serologically diagnosed by an enzyme-linked immunosorbent assay (ELISA), and by viral cultures and histological studies. Among the 52 patients who were evaluable for CMV infection, one had a primary infection and 24 had CMV reactivation/reinfection after BMT. In the latter patients, increases to supranormal levels were observed in T8+ T cells and HNK1+ T cells, both in patients on CyA and in patients on MTX. Double-marker immunofluorescence revealed that the two markers were largely expressed by the same cells, which therefore had the T8+ HNK1+ phenotype. In addition, the very small subset of T4+ HNK+ T cells was slightly, but consistently, increased in the patients with CMV reactivation/reinfection. CMV infection did not influence the numbers of T4+ HNK1- and T8+ HNK1- T cells. The long-lasting presence of large numbers of T8+ HNK1+ T cells in patients who had CMV reactivation/reinfection suggests a continuing interaction between the virus and the immune system of its host.

Adolescent↗
PubMed1984

[Current status of allogenic bone marrow transplantation in chronic myelocytic leukemia].

Bone marrow transplants were carried out in 18 patients with chronic myelogenous leukemia (CML) in the chronic phase (CP). 12 (67%) are still alive, 11 without evidence of leukemia after a mean observation period of 24 (3-44) months, 1 relapsed and 6 died. The most frequent cause of death was GvHD and interstitial pneumonia (5). 1 patient died of septicemia. 2 grafts were performed in patients with CML in the accelerated phase (AP); both died, one from leukemic relapse and one from GvHD. The authors also participated in an international study in which 117 patients were evaluated. In CP there was a survival plateau at 63%, in AP at 36% and in blastic crisis at 12%. In CP mortality was primarily age-dependent and relapses occurred in only 7%. It is concluded that bone marrow transplantation (BMT) is a highly successful treatment for CML, with the CP the optimum moment for grafting. Longlasting cytogenetic and clinical remissions with potential for cure are possible in a high percentage of patients. The incidence of transplant-related mortality is acceptable. The incidence of leukemic relapse is low in CP. Patients under age 40 with HLA-identical siblings should be transplanted in CP. At present BMT is the only treatment with curative potential for CML.

Adolescent↗
PubMed1984

[Acyclovir in the therapy of herpesvirus infections].

Intravenous acyclovir was tested both prophylactically and therapeutically in herpes infections in 48 patients undergoing bone marrow transplantation. Pretransplant prophylaxis only partly eliminated reactivated infections. Treatment of established mucocutaneous infections was usually successful, also in relapsing cases, when initiated within hours of the appearance of lesions. Extensive lesions, superinfections and dissemination could thus be prevented in this group of severely immunocompromised patients.

Acyclovir↗
PubMed1983

[Bone marrow transplantation in acute lymphatic leukemia during the first remission].

9 patients with acute lymphoblastic leukaemia (ALL) were transplanted in first remission. There were no leukaemic relapses and 6 patients became longterm survivors. Causes of death were GvHD in 2 and interstitial pneumonia in 1. 14 patients with ALL were grafted in later stages of the disease. 10 had a leukaemic relapse. One attained longlasting remission with chemotherapy, while 9 died. One patient died of CMV infection. Cotton wool lesions and haemorrhages in the retina posed a problem in patients with previous cranial irradiation. We recommend transplantation of ALL in first remission if a syngeneic or HLA-identical sibling is available, particularly if the patient has poor risk factors for chemotherapy. Prophylactic cranial irradiation should be replaced by intrathecal methotrexate and/or cytosin arabinoside in these patients.

Adolescent↗
PubMed1983

[Bone marrow transplants--quo vadis?].

Early bone marrow transplantation (BMT) in leukaemia has enormously improved the results. Leukaemic relapse is rare, as is transplant-related mortality from interstitial pneumonia and severe graft-versus-host disease (GvHD). In aplastic anaemia the most important development is that treatment with ALG offers a real alternative to BMT which is of crucial importance for all patients without a histo-compatible family donor. The main problems of BMT are the lack of histocompatible donors and GvHD. In leukaemia, relapse is still an additional problem. The new immunosuppressive agent cyclosporin-A (CyA) has made an important contribution to the prophylaxis of severe GvHD. In future the results with CyA are potentially improvable by combination with other immunosuppressive agents. It is important that the use of HLA-semicompatible family donors, unrelated donors or alternative stem cell sources should become feasible. The value of autologous BMT is difficult to judge because in most instances it has been performed in patients with endstage disease. In several congenital diseases there are alternatives to BMT, such as genetic engineering. Although many problems of BMT still have to be solved, this procedure has an important place in modern medicine.

Bone Marrow Transplantation↗
PubMed1983

[Bone marrow transplantation in leukemia and aplastic anemia].

In a review of allogeneic bone marrow transplantation (BMT) for leukemia the following points proved to be of crucial importance: (1) combination of cyclophosphamide (Cy) and total body irradiation (TBI) for conditioning, (2) early BMT for acute leukemia (AL) in first remission and for chronic granulocytic leukemia (CGL) in chronic phase, (3) prophylaxis of graft-versus-host disease (GvHD) with cyclosporin-A (CyA). 50 successive BMT for leukemia performed in Basel between July 1979 and September 1982 are analyzed. 7 of 13 acute myelogenous leukemias (AML) and 8 of 9 acute lymphatic leukemias (ALL) grafted in first remission, and 7 of 10 CGL, are alive without signs of leukemia and without chronic problems. Of the patients grafted for AL in second remission or later, 3 of 6 AML and 6 of 12 ALL are alive. Severe GvHD was seen in 5 of 43 BMT between HLD identical siblings, in three of them combined with interstitial pneumonia. Thus the incidence of these two serious complications of allogeneic BMT has been drastically reduced with CyA compared to our previous experience with prophylactic methotrexate (MTX). 4 grafts were performed between HLA-haploidentical siblings. 3 of the 4 patients developed fatal GvHD. This implies that in this histocompatibility setting CyA alone is not sufficient. No problems were encountered in 3 syngeneic BMT. 12 leukemic relapses were observed. Relapse never occurred in ALL in first remission and never in CGL. 4 recurrences were seen in AML in first remission. All other relapses were in patients with AL grafted in stages other than first remission. In 86 successive patients with severe aplastic anemia (SAA) the following important advances were made: (1) it was shown that the majority of patients have sufficient hemopoietic stem cells and that after treatment with antilymphocyte globulin (ALG) over 70% have long-lasting remissions, (2) the combined treatment with ALG and high dose prednisone increases the remission rates to 90% and in addition shortens the supportive care period significantly. These developments are of crucial importance for patients without an HLA-identical sibling, (3) success rates of marrow transplants between HLA-identical siblings could be increased from 36% with prophylactic MTX to 67% using CyA.

Anemia, Aplastic↗
PubMed1983

Bone marrow cell dose and kinetics of recovery following allogeneic marrow transplantation in man.

In 50 patients transplanted for acute or chronic leukemia we studied the correlation between the number of infused bone marrow cells/kg recipient body weight and the time needed for engraftment. Engraftment was arbitrarily defined as the first day of 1 X 10(9) leukocytes/l and of 20 X 10(9) reticulocytes/l after the posttransplantation nadir. There is a negative non-linear correlation between the duration of leukopenia following marrow transplantation and the amount of transfused nucleated cells (p = 0.01). Since the incidence of infectious or hemorrhagic complications depends directly on the duration of aplasia it is justifiable to give a maximal cell dose.

Acute Disease↗