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Biomedical subjects

V A Kunst

Publications and source records attributed to V A Kunst.

At least 19 recordsLinked to original sources

Prevention of primary cytomegalovirus infection after allogeneic bone marrow transplantation by using leukocyte-poor random blood products from cytomegalovirus-unscreened blood-bank donors.

Cytomegalovirus infection was studied in 59 seronegative recipients of bone marrow depleted of lymphocytes by counterflow centrifugation. Eighteen patients died within 3 months after bone marrow transplantation without evidence of CMV infection, and they were excluded from analysis. Twenty-eight valuable seronegative patients received marrow from a seronegative donor, and 13 from a seropositive donor. All but 2 patients received acyclovir orally (4 x 400 mg/day) from days -9 to +60. CMV prophylaxis with immunoglobulin preparations was not given. All blood products were prepared from random, CMV-unscreened blood-bank donors. The red cell concentrates were depleted of leukocytes by filtration, and leukocytes were removed from the platelet concentrates by centrifugation. None of the patients with seronegative donors showed any clinical sign compatible with CMV infection. Two nonfatal primary CMV infections occurred in the recipients of bone marrow from CMV-positive donors. One of the 59 patients developed interstitial pneumonia, in this case caused by Pneumocystis carinii. Leukocyte depletion of blood products from random CMV-unselected blood donors appeared to prevent primary infection in CMV-seronegative BMT recipients. We conclude that prophylactic use of immunoglobulin preparations is not necessary to prevent CMV primo-infection in patients receiving leukocyte-depleted blood products and acyclovir prophylaxis during the first 2 months postgrafting.

Blood Donors

Immune hemolytic anemia associated with tolmetin and suprofen.

This article reports the first case of immune hemolytic anemia possibly associated with the ingestion of suprofen. The patient suffered from massive hemoglobinuria and acute renal failure. Serologic studies of the patient's serum revealed suprofen-dependent red cell antibodies. However, tolmetin-dependent antibodies were also found in the serum, showing the same properties as the suprofen antibodies and an even higher titer. The patient not only had drug-dependent antibodies in the serum, but also had developed autoantibodies, a phenomenon that has been described for several other drugs. The working mechanism by which suprofen and tolmetin caused immune hemolysis had properties of both the immune complex model and the induction of autoimmunity. Although it was unclear whether the immune hemolytic anemia was the result of suprofen, tolmetin, or cross-reacting antibodies, we feel that suprofen should be added to the list of nonsteroidal anti-inflammatory drugs associated with a positive direct antiglobulin test.

Anemia, Hemolytic, Autoimmune

Host and donor erythrocyte repopulation patterns after allogeneic bone marrow transplantation analysed with antibody-coated fluorescent microspheres.

Analysis of erythrocyte populations, using red blood cell antigen differences between host and donor as marker, was performed with a sensitive fluorescent microsphere assay to monitor marrow engraftment and mixed red cell chimaerism after allogeneic bone marrow transplantation (BMT). An adapted transfusion policy, using marker negative erythrocyte transfusions, was required for this analysis. In all patients the marrow graft was depleted of lymphocytes by counterflow centrifugation. Thirty-seven patients were evaluable for donor repopulation at one or more points in the first 6 months after BMT. At 0.5 month donor erythrocytes were detectable in 19 out of 22 patients. At 6 months donor erythrocytes were detectable in 100% of the evaluable patients. In the first 3 months after BMT the average donor erythrocyte repopulation in recipients of major ABO mismatched transplantations was delayed. Thirty-eight patients were evaluable for chimaerism at 6 months or later after BMT. A high incidence of mixed red cell chimaerism was observed varying from 50% to 71% at different points of analysis. Mixed red cell chimaerism with low percentages (less than 1%) of host cells was not related with relapse, nor did high percentages (greater than 10% of host cells necessarily indicate relapse.

ABO Blood-Group System

A fluorescent microsphere method for the investigation of erythrocyte chimaerism after allogeneic bone marrow transplantation using antigenic differences.

A method for the investigation of erythrocyte chimaerism in patients after bone marrow transplantation (BMT) has been developed using fluorescent microspheres coated with anti-human IgG. Blood group antigens different in patient and donor were used as marker. The specificity and reliability of this method was evaluated measuring artificial mixtures of blood group positive and negative red cells. Red cell antigens tested were D, c, K, Fya, Fyb, Jka, Jkb, S and s. Mean linear regression lines for mixtures with percentages positive cells ranging from 0.01 to 1% and 1 to 100% were 0.91X-0.03 (r = 0.99) and 1.00X-0.05 (r = 0.99), respectively. The sensitivity level of the assay was one positive cell per 10,000 blood group negative cells. In negative control samples (n = 15) a mean percentage positive cells was found of 0.002 +/- 0.004 (SD). Intra- and inter-assay coefficients of variation were 4.9 and 5.3% for mixtures of 10%, and were 11.1 and 24.6% for mixtures of 0.1% blood group positive cells. It is concluded that the described method can be used both to establish the take of donor marrow in an early phase after transplantation and to investigate mixed erythrocyte chimaerism long after BMT.

Antibodies, Anti-Idiotypic

Erythrocyte repopulation after allogeneic bone marrow transplantation. Analysis using erythrocyte antigens.

Blood samples from 31 of 50 consecutive patients receiving bone marrow from an HLA-identical and mixed lymphocyte culture-nonreactive sibling were investigated for the presence of donor and autologous erythrocytes. Simple serological techniques using antigenic differences between donor and recipient and a blood transfusion policy taking these differences into account made this study possible. A total of 71% of the patients had donor erythrocytes demonstrable 4 weeks after bone marrow transplantation; almost all patients did so after 2 months. Disappearance or absence of donor red cells indicated poor patient prognosis. Persistence or reappearance of autologous erythrocytes in small percentages (0.05-10%) occurred without relapse of leukemia. Reappearance in high percentage (50-100%) indicated relapse.

Antigens, Differentiation

HLA-typing and lymphocyte population studies in patients with multiple sclerosis.

Compared to a control population, the frequency of HLA-B7 was increased in a group of 46 patients with a chronic progressive form of multiple sclerosis (MS) (RR = 2.9, P = 0.01). Significance of the association was lost after correction for first order error. Results on serotyping for "B-cell DW2" antigen are suggestive of an increased frequency of this antigen in chronic progressive MS patients (RR = 2.9, P = 0.01). The percentage of T-cells (E-rosette forming lymphocytes) in MS patients was lower (mean 46 +/- 17%, n = 34) than in a control group (mean 62 +/- 10%, n = 90). Only 5 of the 40 patients had high B-lymphocyte percentages, whereas no difference in B-cell counts was observed between the total group of patients and the control group. The T- and B-lymphocyte ratio in the MS patients was lower than in the control group. The 7 patients, with the lowest T/B-cell ratio were negative for "B-cell DW2" antigen. In 3 patients, the sum of T plus B-lymphocytes was far lower than 90%. At least 4 patients had in their serum antibodies against autologous lymphocytes as found by immunofluorescence tests. No correlation could be found between these serological and immunological data and clinical data on progression of the disease, the IgG in CSF and improvement after immunosuppressive treatment.

Antigens

Successful haemodialysis and renal transplantation in a patient with haemophilia A.

A 19-year old male with severe haemophilia A (factor VIII activity less than 1%) developed terminal renal insufficiency and was subsequently dialysed via an external arteriovenous shunt for one year. To prevent bleeding he received cryoprecipitate (2000-2500 units of factor VIII) three times a week during dialysis. After one year of uneventful dialysis he received a kidney graft from a cadaver donor that was matched for the B locus antigens. During the first two weeks after transplantation his factor VIII level was kept at approximately 70% by daily cryoprecipitate infusions. Thereafter he was free from bleeding at a level of 20% with prophylactic cryoprecipitate treatment (1000 units 3 times a week). He was discharged from the hospital five weeks after transplantation with excellent renal function (ECC 75 ml/min). No rejection crisis occurred. His factor VIII requirements remained unchanged after transplantation, indicating that the human kidney does not substantially contribute to the production of clotpromoting factor VIII.

Adult