Biomedical subjects
B M Eggen
Publications and source records attributed to B M Eggen.
Self-sufficiency for plasma and plasma proteins in Norway.
Self-sufficiency has been achieved in Norway with regard to all major blood products even with the collection of only 41,906 units of whole blood and 2,586 plasmapheresis sessions per million inhabitants (1994). Since 1989 the collaborative effort of the 'Norwegian Fractionation Project' has secured the self-sufficiency of virus-inactivated plasma and (high/ ultra-high purity) products of plasma proteins. Thus national self-sufficiency for plasma can be obtained by a combination of national guidelines, close collaboration to the clinicians, and a limiting plasmapheresis programme combined with the preparation of FFP from the majority of whole blood collections.
[Blood transmission and infections].
A blood transfusion can never become a completely risk free event. Almost all kinds of infectious agents; viruses, bacteria and parasites, can be transmitted by blood. So far, hepatitis and HIV-infections have been focused. The state of readiness to meet these infections must be kept while we prepare for "new" agents, like parvovirus B19. Extensive international travelling will increase the possibility of blood-borne parasitic infections, like malaria and Chagas' disease, even with the very high quality demands imposed for Norwegian blood donors. We can keep a better eye on the infectivity of the blood products by strictly realizing our objective of national self-sufficiency. Recent research results indicate transfusion-mediated effects to the immune system, particularly of allogeneic transfusions containing leucocytes. This immunomodulation seems to enhance the risk of secondary infections. So far, it is impossible to tell whether this immunomodulation has any impact on the long-term outcome of malignant diseases. A blood transfusion will always represent a risk, although small, to the patient. This recognition makes it essential to carefully consider whether to give a patient a transfusion, and to document this decision properly.
Distributions of HLA class II alleles in autoantibody subsets among Norwegian patients with systemic lupus erythematosus.
In order to find potential correlations between HLA class II alleles and anti-SS-A, -SS-B, -Sm and anti-snRNP responses among Norwegian patients with systemic lupus erythematosus (SLE), HLA-DRB1, -DRB3*0101, -DQA1 and -DQB1 alleles were determined by DNA typing 50 patients and 108 controls. HLA distributions were analysed in the following autoantibody subgroups: anti-SS-A with -SS-B, anti-SS-A without -SS-B, anti-snRNP without -Sm, anti-SS-A without -snRNP and anti-snRNP without -SS-A. The autoantibodies were detected by EIA (enzyme immunuassay). Patients with anti-SS-A and -SS-B had significantly increased frequencies of DRB1*03, DRB3*0101, DQA1*0501, DQB1*0201 (in linkage disequilibrium) versus controls and versus patients without anti-SS-A and -SS-B. No differences in HLA distribution were found when the group with anti-SS-A alone was compared to the group with anti-SS-A and concomitant -SS-B. Comparing the groups with and without anti-SS-A and -SS-B, the highest RR were found for the alleles DRB1*03, DRB3*0101, DQB1*0501, DQB1*0201 (in linkage disequilibrium) with RR: 16.8, 5.0, 19.6, 10.3, respectively, P < 0.05). RR for DQw2/DQw6 heterozygotes was 3.5 (Ns.), and RR for cases having DQ alpha molecules with glutamine in position 34 and DQ beta molecules with leucine in position 26 on both chains was 6.3 (P < 0.05). No HLA associations were observed in the group with anti-snRNP without concomitant -Sm or without concomitant -SS-A. These results show that production of anti-SS-A and -SS-B is associated to the HLA alleles DRB1*03, DRB3*0101, DQA1*0501, DQB1*0201, and that this haplotype shows stronger correlation to these responses than DQw2/DQw6 heterozygosity or HLA molecules having glutamine in position 34 (DQ alpha) and leucine in position 26 (DQ beta). The failure to observe any correlation with DRBI*15,16 (DR2) in the group with anti-SS-A alone may demonstrate ethnic differences concerning this response. The failure to identify any HLA associations for the anti-snRNP response may reflect the heterogeneity of the molecules that constitute this antigen.
[Health risks of vaccination of farmed fish].
In 1991, three cases of anaphylactoid reactions among vaccinators of farmed fish were registered in Norway. The reactions developed after repeated accidental self-injection of vaccine against salmon furunculosis. In 1991, some 60 million salmon were vaccinated against furunculosis at approximately 50 grams body weight. Following such self-injection of vaccine, inflammatory reactions are seen in the injected finger, also spreading occasionally to the hand. More seldom a "flu" like syndrome with fever, muscle aches, and general malaise is experienced probably caused by endotoxins in the vaccine. Devices to protect the fingers against accidental self-injection have been developed and, so far, the results are promising.
[Cytomegalovirus and blood transfusion].
Cytomegalovirus infection can be transmitted by transfusion of leucocyte-containing blood products (i.e. red cells and platelets). In otherwise healthy persons this virus infection causes a mild mononucleosis-like syndrome. In immunocompromised patients (neonatal patients if birth weight is less than 1200 grams; immunodeficiencies; haematological malignancies; bone marrow transplanted patients) a cytomegalovirus infection can be fatal. The transmission of cytomegalovirus by blood can be avoided by using seronegative blood donors. Recent experiences indicate that efficient removal of viable leukocytes by filtration (which removes more than log-3 of leukocytes) will prevent transmission of cytomegalovirus infection even when using blood from seropositive blood donors. All cellular blood products for the risk groups must be filtrated in any case, to avoid HLA-immunization and graft-versus-host reaction. Since this filtration seems to prevent the transmission of cytomegalovirus, the cost of screening of blood donors for anti-cytomegalovirus-antibodies is an unnecessary expense.
[Distribution of physicians--with intentional prejudice?].
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Transmission of HCV by organ transplantation.
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Congenital diaphragmatic hernia: determination of the optimal time for operation by echocardiographic monitoring of the pulmonary arterial pressure.
Preoperative stabilization and delayed operation rather than emergency repair of congenital diaphragmatic hernia (CDH) may improve survival, but there are no clear criteria for how long operation should be delayed. Because increased pulmonary vascular resistance (PVR) may be an important risk factor, we used Doppler echocardiography to study patients with CDH presenting with respiratory distress immediately after birth. During the study period 10 patients were admitted, but 2 were moribund on admission and died shortly thereafter. In the remaining patients the pulmonary arterial pressure (PAP) and direction of ductal shunt were estimated by Doppler echocardiography. Initial PAPs were in the range of 45 to 90 mm Hg, with bidirectional or right-to-left shunt through the ductus arteriosus. Reduction of pressure to 25 to 55 mm Hg, or reversal of shunt to left-to-right, reflecting decreased PVR, occurred after ventilation for 3 to 20 days (mean, 8 days). Patients underwent operation after there was evidence of reduced PVR. None developed persistent fetal circulation, and all 8 patients survived. We conclude that postponing operation until PVR has decreased seems to improve survival in patients with CDH presenting within hours of birth.
Recurrent glioblastoma treated by chemotherapy alone.
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[Interferons and their physiological significance].
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In vitro effects of leukocyte interferon on the cytotoxic potential of human monocytes.
The in vitro cytotoxicity of human monocytes was enhanced by leukocyte interferon (IFN-alpha). In contrast to lymphokine activation which is obtained gradually under long-term contact with monocytes, maximal activation of effector cells was obtained within 4 hours of culture with IFN-alpha prior to medium exchange and target cell addition. The degree of activation was clearly dose-dependent, reaching a plateau level of cytolysis at 400 U/ml of IFN-alpha. In cytostasis no such plateau was demonstrable. IFN-alpha enhanced the level of cytolysis mediated by human monocytes without inducing any change in the kinetics of lysis, regardless of whether IFN-alpha was used for activation of monocytes prior to or simultaneously with the cytolysis assay. The direct effect of IFN-alpha on K-562 target cells was sparse. The incorporation of thymidine was modestly depressed in the presence of IFN-alpha. Exposure of K-562 cells to IFN-alpha did not have any effect on the spontaneous isotope leakage from prelabelled target cells. The exposure of K-562 cells to IFN-alpha prior to the start of co-culture with monocytes did not change the level of cytolysis reached, either with non-activated or with IFN-alpha activated monocytes, and irrespective of the in vitro age of the monocytes. The effect of IFN-alpha thus seems to be mediated via the effector cell population and not via target cell modulation.
Dissociation between cytostatic and cytolytic activity of human monocytes towards K-562 cells.
The cytolytic and cytostatic activities of human monocytes towards K-562 cells were compared by determining release of 3H-thymidine and DNA synthesis rate (i.e. thymidine incorporation), respectively. The inter-individual variations were substantial, with significant correlation between cytostasis and cytolysis in the entire experimental material (26 blood donors), but not in monocytes kept in vitro for 90 min or 1 day before the start of assay. A significant level of correlation between cytolysis and cytostasis was observed in monocytes kept in vitro for 4 days before assay (coefficient of correlation = 0.7). The low degree of correlation at each test-time-point prohibits the prediction of cytostatic capability of human monocytes in individual experiments from determination of monocyte-mediated target cell lysis.
Depression of monocyte-mediated cytotoxicity by renal carcinoma and restoration through therapy.
The cytotoxic ability of freshly isolated monocytes against the tumor cell line K-562 was severely depressed in patients with renal cell carcinoma. The impaired cytotoxicity was partly restored 2 weeks after nephrectomy. Production of monocyte-activating lymphokine, measured as ability to activate tumor cytotoxicity in control monocytes, was depressed in lymphocytes from patients with tumor burden. The impaired lymphokine production seemed to be due to factors in patient serum. Patient monocytes showed an impaired ability to be activated by lymphokines. Products from patient lymphocytes were not able to activate the tumor cytotoxicity of patient monocytes.
Soluble cytostatic factor(s) released from human monocytes. II. Effects on target cell kinetics.
Human monocytes release a stable cytostatic factor during in vitro culture after stimulation with lymphokine and endotoxin. The cell cycle time of synchronized NHIK 3025 cells increased from 20.3 to 23.2 h in the first cell cycle when the target cells were exposed to the factor during the whole cell cycle. In exponentially growing NHIK 3025 cell cultures the cell doubling time increased from 18.9 h to 23.1 h under continuous factor exposure for 70 h. These cells regained normal cell division rate when fresh culture medium replaced the cytostatic factor. Continuous exposure to the cytostatic factor for 96 h increased the cell doubling time of asynchronous K-562 cells from 19.7 to 31.8 h. The target cell DNA synthesis, evaluated by thymidine incorporation, was markedly depressed after culture with the factor for 24 h, and this depression was detectable already within 4 h of culture. The factor showed no cytolytic effect on the two cell lines tested. The cytostatic factor influenced the cell cycle distribution of both target cells tested, since cell cycle analysis by DNA flow cytometry demonstrated a reversible inhibition of factor-exposed NHIK 3025 cells in G1- and early S-phase, whereas K-562 cells accumulated in G1-phase.
Cytotoxicity of temporarily adherent human mononuclear blood cells in monocyte monolayers.
Adherent monolayers of freshly isolated human peripheral blood mononuclear cells consist mostly (greater than 90%) of monocytes. The initially adherent nonmonocytic cells detach during the first day of in vitro culture. Concomitant with cell detachment the cytotoxicity mediated by adherent monolayers is reduced. This is in part due to medium exchange with removal of initially adherent cells from the monolayers, cells that are potent mediators of cytostasis and cytolysis. The temporarily adherent cells consist of 10% monocytes, 35% T lymphocytes, 10% B lymphocytes, and 45% non-T, non-B lymphocytes. In addition, 45% of these cells stain positively with the monoclonal antibody OKT 10. The reduction in monolayer-mediated cytoxicity from day 0 to day 1 of in vitro culture is less pronounced if the temporarily adherent cells are kept within the culture during the cytotoxic assay time. When the temporarily adherent cells are returned to adherent monocyte monolayers an additive effect on cytolysis is demonstrated with nonactivated, lymphokine-activated and alpha-interferon-activated effector cells, and in antibody-dependent cell-mediated cytotoxicity. The heterogenous population of temporarily adherent cells in freshly isolated monolayers of human mononuclear blood cells seems to be responsible for some of the cytotoxic effects regularly ascribed to freshly isolated human blood monocytes.
Inhibitory effect on monocyte-mediated cytotoxicity of sera from patients with multiple myeloma and malignant lymphoma.
There was no difference in monocyte-mediated cytotoxicity between monocytes from patients with multiple myeloma or malignant lymphomas and monocytes from control persons after in vitro culture for 5 d. Cytostatic and cytolytic ability of lymphokine-activated monocytes cultured in medium with patient serum was significantly depressed compared to the ability of monocytes cultured with normal serum. A similar depression of cytostasis was found with non-activated monocytes of both patient and control origin. Sera from myeloma and lymphoma patients impaired the monocyte-mediated cytotoxicity equally.
Cytotoxicity of temporarily adherent human mononuclear blood cells. 1. Cytotoxic abilities of cells after detachment from culture wells.
Monolayers of freshly isolated peripheral blood monocytes are contaminated with 5-10% non-monocytic cells. These cells detach during the first day of in vitro culture, concomitant with a disappearance of the strong cytostatic and cytolytic activity of freshly isolated monocytes. The detached cells, mostly non-monocytic cells, exerted cytostasis and cytolysis on the human natural killer (NK) sensitive cell line K-562. The lytic activity was sensitive to trypsin treatment. The kinetics of cytolysis was NK-like, with maximal 51Cr-release within 4-8 hours of co-culture, and with a high degree of methyl-3H-thymidine release during the first 24 hour of co-culture, and with a high degree of methyl-3H-thymidine release during the first 24 hours of co-culture. It is suggested that these cells may be a loosely adherent subpopulation of mononuclear cells with NK-like properties.