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Human lymphocytes were reacted with antisera against β-2-microglobulin (β-2-m) or HL-A antigens, and with xenogeneic anti-lymphocyte sera under conditions where redistribution and aggregation of the corresponding cell-membrane components were induced. The results demonstrate that: 1) Treatment with anti-β-2-m antisera aggregated and completely removed the HL-A anti-genic structures from the cell membrane, but not, however, the structures reactive with anti-lymphocyte sera. 1) Treatment with anti-HL-A antisera also aggregated some of the β-2-m carrying structures, but left others undisturbed. 1) Treatment with anti-lymphocyte sera did not disturb expression of HL-A antigens or β-2-m structures. 1) Anti-β-2-m and anti-HL-A antisera inhibited antigen activation of lymphocytes, but this was not so in the case of the anti-lymphocyte sera used. 1) The anti-β-2-m antiserum and the anti-lymphocyte sera were mitogenic for normal lymphocytes. Taken together, our results strongly suggest that β-2-m is also part of native cell-membrane bound HL-A antigens, and that the antigenic structures which react with xenogeneic anti-lymphocyte sera may reside on molecules separate from those carrying HL-A and β-2-m activity. Furthermore, the results indicate that the two sub-unit molecules consisting of HL-A alloantigenic determinants and β-2-m are closely associated — structurally or functionally — with lymphocyte receptor structures.

Delay between blood collection and the separation of its components may result in lowered yield of factor VIII (FVIII) and loss of 2,3-biphosphoglycerate (2,3-BPG). This study was to see whether the use of 0.5 CPD resulted in better preservation of FVIII and maintenance of 2,3-BPG.55 units of blood were collected in 0.5CPD and 48 in CPD SAG-M. Ten of the collections were paired, so that the same donors were bled in a single session partly in an 0.5CPD system and partly in CPD SAG-M. After collection, the blood was promptly cooled to 20 degrees C and stored at that temperature for up to 24 h.Preservation of FVIII activity was significantly better in 0.5CPD compared with CPD. The content of von Willebrand factor was stable in the anticoagulant solutions for 24 h at that temperature. Plasma separated from both media had how levels of prothrombin fragment 1 + 2 and complement activation. Paired collections substantiated previous reports that red cell storage is significantly improved in 0.5CPD compared with CPD SAG-M with respect to 2,3-BPG and haemolysis.Red cell metabolism and oxygen-releasing capacity are kept at acceptable levels in 0.5CPD blood for 24 h at 20 degrees C before component separation. The concentration of red cell 2,3-BPG remained at normal or slightly subnormal levels during further storage in 0.5CPD at 4 degrees C for 2-4 weeks before gradual decay to an average of 39% at 48 days.

For 30 years it has been known that immunodeficient patients can have a fatal reaction to transfused blood components containing viable lymphocytes. This risk of a transfusion-associated graft-versus-host reaction can be totally eliminated by irradiation of the blood prior to transfusion. Immunocompetent individuals can have this potentially fatal reaction if the blood donor is homozygous for one of the HLA-haplotypes of the recipient. The probability of this coincidence is low when donor and recipient are unrelated, but considerably higher when they are genetically related. When HLA-matched blood platelets are indicated for transfusing patients refractory to random platelets, the platelets must always be irradiated with minimum 25 Gy, since a large proportion of the donors will be homozygous with one of the HLA-haplotypes of the recipient.

Infusion of haematopoietic stem cells, either autologous or allogeneic, allows treatment of malignant diseases with marrow ablative doses of cytostatics or whole body irradiation. Hospitalization and general anaesthesia is necessary for bone marrow harvesting, while the harvest of peripheral stem cells may be performed without hospitalization. Mobilization of haematopoietic stem cells from the bone marrow to peripheral blood, followed by cytapheresis and harvesting of the stem-cell containing fraction is a promising alternative to the harvest of marrow. We have tried this in one patient with advanced acute myeloid leukaemia and discuss our experience and that of others.

Medical coding and classification systems are expected to become increasingly important in the health care sector. Together with and as an integrated part of the electronic health information systems, the coding and classification systems will be used to improve the quality and effectiveness of the medical services. Activities connected to the different coding and classification systems are a very important component of the attempts at standardization taking place both in Norway and in the rest of Europe within the discipline medical informatics. These activities must be secured a proper professional and economic foundation. It is also of vital importance that national health authorities should participate in these activities and establish formal cooperation with professional bodies. In Norway, the Ministry of Health and Social Affairs has accepted with some miner modifications, our suggestion for a model where the Norwegian Medical Association would be responsible for the medical aspects of the coding and classification systems and for their development, and the Norwegian Centre for Medical Informatic's for organization, distribution, electronic version, integration in information systems and user assistance.

During the period 1985 to 1991 there has been a marked change in consumption of blood, and at the National Hospital the number of transfusions decreased by 52% from 41,747 units. However, the number of admitted patients annually has remained unchanged and the patient pattern includes more complicated cases. We conclude that cost accounting, consumer-adapted reporting, vigilant follow-up and an active transfusion committee are important factors for the changes in blood consumption. Furthermore, the professional attitude towards surgical blood conservation techniques and modern haemotherapy have been consolidated at the hospital concerned.

Quality control of leucocyte depleted blood products has become a problem since the introduction of bedside leucocyte filtration. At our Blood Centre, this problem has been circumvented by testing a sample taken as the filtration is completed by sealing off a 10 cm piece of tubing just under the filter. We have tested four brands of erythrocyte filters, Pall RC100, Erypur Optima b, Sepacell R-200A and Sepacell R-500A(II) using two erythrocyte concentrates for each filter. We have tested two brands of thrombocyte filters, Pall PL100 with 6-8 thrombocyte concentrates, and Sepacell PL-5A with 2-6 concentrates. No transfusion should give more than 5 x 10(6) leucocytes. Pall PL100, Pall RC100 and Sepacell R-500A(II) met the criteria.

In analyses of cost-effectiveness it is customary to count knowledge of having a high serum cholesterol level as a negative factor. There is little support for this practice in the literature. We have studied the attitude of 305 Norwegian blood donors towards cholesterol testing. 63% stated that they were interested in their serum cholesterol level, and 40% said they knew their own serum cholesterol level. The attitude towards cholesterol testing was clearly positive, both among men and among women, regardless of age. Only one donor stated that she did not want to have her serum cholesterol tested in conjunction with blood donation.

Serum cholesterol levels were measured in 280 blood donors between November 1988 and May 1989 and again between February and April 1991. In 84 of these persons the cholesterol level was also measured between November 1989 and January 1990. The 122 females showed a 9.6% reduction in mean serum cholesterol from 5.8 mmol/l in the first sample to 5.2 mmol/l in the final sample. The 158 males showed a 7.4% reduction from 5.7 to 5.3 mmol/l. Females with initial values greater than 6 mmol/l showed an average reduction in serum cholesterol of 15.2%. For males with initial values greater than 6 the reduction was 14.0%. There was no difference in reduction between those whose cholesterol was measured at the beginning and the end of the study and those whose cholesterol was also controlled during the course of the study. Our study shows that, in the case of blood donors, a programme involving measuring serum cholesterol and distributing written information can lead to a substantial reduction in serum cholesterol.

We present short and long-term results of allogeneic bone marrow transplantation after hyper-fractionated total body irradiation and high dose cyclophosphamide in ten patients treated for leukaemia during the period 1985-89. Three patients died from complications connected to the transplantation, while seven are living free from leukaemia 18 to 59 months after transplantation (mean 41 months). Two patients need treatment for chronic graft versus host disease. Allogeneic bone marrow transplantation is expensive and risky. Close cooperation between clinicians and laboratory specialists is essential. The treatment increases long term survival and probably cures certain patients with leukaemia. Some of these patients will need treatment for chronic graft versus host disease and other late sequelae.

In the present study the effect of a change from whole blood to plasma donation on iron stores is investigated by measuring serum ferritin levels. Paired serum samples from 125 plasma donors showed a significant increase in mean serum ferritin level with plasmapheresis. 76% of the plasma donors showed an increase in serum ferritin. For plasma donors the haemoglobin concentration is not related to serum ferritin level and hence to iron stores, and a change in haemoglobin concentration is not related to a change in serum ferritin. Plasma donation is a good alternative to whole blood donation for fertile women and for blood donors opposed to iron supplements.

We present the results of serum-cholesterol measurements in 956 blood donors and an evaluation of their motivation for dietary changes based on answers to a questionnaire. The mean serum-cholesterol level was 5.5 mmol/l for women and 5.7 mmol/l for men, with an increase in serum-cholesterol with age. Motivation for dietary changes was food, since 85% answered that they would change their diet if their serum-cholesterol was high. 65% of those who knew their serum-cholesterol to be high before this study had changed their diet. 38% of the smokers answered that they would stop smoking if their serum-cholesterol was high. Eight to 14 months later, serum-cholesterol measurements in 201 of the blood donors showed that 72.4% of those with serum-cholesterol greater than 6 mmol/l had changed their diet and that these had reduced their serum-cholesterol by an average 10.6%.

Since 1986, we have performed 26,500 plasma donations at the Red Cross and National Hospital Blood Centre. In conjunction with these donations, 4,000 serum samples from 3,400 donors have been tested for IgG and albumin level. 125 donors who donated plasma regularly were studied further. In this group we found a mean reduction in IgG of 0.3 g/l, but no significant reduction in albumin. Even for donors who donate regularly the mean time interval between donations was more than 40 days. Today's recommendation of regular IgG and albumin control is a result of experiences from twice weekly plasma donations in the USA. We conclude that such testing is unnecessary in Norway.

In the present study we have examined serum ferritin in experienced male and female blood donors and in women who had never donated blood before, but had registered at the Blood Centre as future donors. There was no coincidence between low haemoglobin and low s-ferritin when haemoglobin was within normal range. Iron stores (s-ferritin less than 20 micrograms/l) were reduced in 40% of the female blood donors and in 21% the iron stores (s-ferritin less than 10 micrograms/l were completely empty. 10% of the male donors had iron stores, while in 3% the iron stores were empty. Among the females who had not donated blood, 30% had s-ferritin values below 20 micrograms/l and 6% had values below 10 micrograms/l. We conclude that measuring s-ferritin is a better method of identifying individuals at risk for iron depletion than measuring hemoglobins. A combination of longer intervals between donations and iron therapy may prevent depletion of iron stores in blood donors.

This paper presents both quality requirements and indications for use of leucocyte-filtered, cytomegalovirus antibody negative and irradiated cellular blood products at Rikshospitalet. Emphasis is placed on the use of standardized buffycoat depleted red cells or platelet concentrates for filtration, and the selection of leucocyte filters with high capacity and ease of bedside application. Leucocyte counts as low as 1-2 10(5) per unit are recommended after filtration in order to avoid HLA-antibody production. For bedside filtration, our choice was RC100 and PL100 (Pall) for red cells and platelets respectively. For laboratory use we prefer, for economic reasons, to use Sepacell R500 (Asahi) and Imugard IG500 (Terumo) for red cells and platelets respectively. Leucocyte-filtered blood products are considered indicated in all pre-transplant transfusions, in post-transplant HLA-sensitized patients, in other patients with febrile transfusion reactions, and in patients with an expected protracted platelet requirement. CMV antibody negative products are recommended for all immuno-deficient patients and pregnant women negative for CMV antibody. Irradiated blood products are used in the treatment of immuno-deficient patients receiving large amounts of blood, and in all severely immuno-compromised patients. In emergency situations where CMV antibody negative and/or irradiated blood products cannot be supplied, leucocyte filtration is suggested.

Two human alloantisera specific to bone marrow-derived lymphocytes (B cells) were shown to precipitate polypeptide chains of 29,000 and 34,000 daltons from human lymphoblastoid B cell lines. These molecules are similar to murine Ia antigens and are also precipitated by a rabbit B-cell specific heteroantiserum. Since the alloantisera are thought to recognize determinants coded by HLA-D or closely linked loci, these data support the hypothesis that these B-cell specific alloantigens are the human counterpart of the mouse Ia antigens and may be the products of HLA-D.

Two brothers with severe combined immunodeficiency were treated with repeated transplantations of fetal thymus tissue. The first patient was not treated until he was critically ill, and the intramuscular transplants had no effect. He died at 11 months of age of overwhelming pneumonia. At postmortem examination a transplanted thymus seemed viable. In the second patient an intramuscular transplant had no effect, but three subsequent intraperitoneal transplants led to transient increase in circulating T lymphocytes with a concomitant fall in B lymphocytes. The results suggested an additive effect of each transplant. However, delayed hypersensitivity skin tests and in vitro mitogen responses were not influenced. Initially, transfer factor was given, and fetal liver was administered intraperitoneally together with the last thymic transplant. Neither of these measures had any observed effect, and this patient, similarly, died of pneumonia at nearly 12 months of age.

The localization of individually specific antigenic determinants on the monoclonal γM Mö was studied in gel diffusion experiments with 19S γM Mö and its 7S subunit. Various types of such determinants were delineated. Some were demonstrable both on the intact macroglobulin molecule and on the subunit. The latter was often unable to precipitate with the corresponding antibody, but combined with it and inhibited precipitation. Immunization of rabbits with purified γMs Mö was the most useful way to obtain antisera demonstrating individually specific antigenic determinants on the subunit by direct precipitation. Still other determinants were apparently destroyed by mild reduction of the γM molecule. Reduction and reassociation of mixtures of two monoclonal γM-globulins resulted in formation of hybrid molecules containing subunits of different origin. Individually specific antisera against the two components were useful for demonstrating hybrid formation. Serological activity, i.e., cold agglutinin activity, was present in the hybrid molecules.

The localization of individually specific antigenic determinants on monoclonal γM Mo was studied in gel diffusion and density gradient ultracentrifugation experiments with its very mildly reduced subunit, papain Fab μ and Fc μ fragments, and the pepsin (ab′) 2μ and Fab′ μ fragments. The subunit and Fab μ were usually unable to precipitate the corresponding antibody, but combined with it and inhibited precipitation of intact γM Mo in gel diffusion. The Fc μ fragment did not react with any of our individually specific antisera. An individually specific antigenic determinant which dependes on the intact disulfide bond bewteen the heavy and light chains in γM Mo is described. This determinant diappeared by reduction of the disulfide bond and alkylation, but reappeared when the bond was reassociated. This determinant was found to be responsible for one of the dual precipitin lines between several of our antisera and highly purified γM Mo.

The inhibitory effect of HLA antisera on Fc receptors of human lymphoid FcRFC and K cells was investigated. Antisera recognizing determinants of the HLA-A, -B, and -C series had no effect on FcRFC, while specific inhibition was observed with an antiserum reacting with determinants closely associated to HLA-DW2. This inhibitory effect was also demonstrated by the Fab' fragments. Specific inhibition of K cells was observed with all HLA antisera, but this effect was lost in the Fab' fragments. We concluded that the Fc receptor of FcRFC may be closely associated with products of the HLA-D region. This is analogous to the association between the Fc receptor and the Ia antigens on murine splenic B lymphocytes.

Sera from 142 Norwegian couples were assayed for the presence of antibody to Cytomegalovirus. Sixty-four percent were seropositive and the yearly conversion rate was approximately 1.65%. The couples included significantly more seropositive women than men. This may indicate that seropositive men infect seronegative women, while seropositive women seldom infect seronegative men.

Protein A from Staphylococcus aureus interacts in a specific manner with most subclasses of human IgG. In the present study a method is described which utilizes Protein A labeled with 125I for the detection of antibody sensitization of platelets. The clinical applicability of the test for detection of in vivo or in vitro sensitization is demonstrated in three patients with platelet antibodies.

Prospective HLA-DR typing and B cell cross-match tests were performed in 177 cadaveric transplants using a modified NIH technique, 24 selected HLA-DR typing sera and B cells separated from peripheral blood in recipients and from spleen in donors. Actuarial graft survival after one year was 60% in HLA-DR compatible transplants and 30% and 18% in transplants mis-matched for 1 and 2 HLA-DR antigens. The favorable prognostic influence of HLA-DR compatibility was observed both among HLA-A, -B compatible and incompatible transplants. Sharing of HLA-DR antigen(s) between donor and recipient was also prognostically beneficial. Standard cross-match tests were negative in all transplants. B cell cross-match tests were positive in 17 cases, and one of these transplants was very acutely rejected. Actuarial graft survival after three months was 35% in B cell cross-match positive grafts versus 53% in negative ones.

The influence of matching for the whole HLA haplotype as well as for the separate HLA antigens controlled by this region, was studied in a material of 98 living related and 178 cadaveric first transplants. Graft survival corresponded closely to the degree of HLA haplotype disparity between donor and recipient. Furthermore, graft survival was less in combinations being incompatible for the serologically defined HL-A and -B antigens as compared to compatible combinations. A weak MLC response between donor and recipient, even in the presence of HL-A and -B disparity, might signify prolonged graft survival.

Passive enhancement was attempted with F (ab') 2-fragments in six patients receiving their first and in one patient the second one haplotype mis-matched kidney graft. Administration of enhancing antibody in the first graft patients seemed safe, the group was however too small to determine whether the enhanced patients did better than those conventionally treated. The only pre-sensitized patient who received his second transplant rejected it during the first week, possibly due to a deleterious effect of the F (ab') 2-fragments.