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Biomedical subjects

A H Balk

Publications and source records attributed to A H Balk.

At least 109 records · Page 6Linked to original sources
PubMed1993

Compliance with the medical regimen and partner's quality of life after heart transplantation.

The authors investigated 40 heart transplant recipients and their partners to determine both the partner's quality of life upon transplantation and the experiences of both patient and partner with compliance with the medical regimen. Data on sleep disturbances, social isolation, emotional reactions, depression, anxiety, partner's apprehension, social support and compliance (regarding behaviour and emotional experience) were obtained approximately 21 months after transplantation. Compared to related study groups, partners did not experience more problems in sleep, social isolation, emotional reactions, depression and anxiety. Patients overestimated the apprehension of their partners significantly (p < 0.0001). Generally speaking, with the exception of three items relating to eating fish, canned food and forgetfulness in medicine intake, patients and partners agreed with respect to actual compliance behaviour. Lowest compliance concerned regular physical exercise: 28%. Both patient and partner insisted that they had scarcely any emotional problem with the regimen. Further systematic research is needed to bring to light factors that affect compliance as well as adequate methods to bring about an improvement therein.

Adult↗
PubMed1993

Donor heart endothelial cells as targets for graft infiltrating lymphocytes after clinical cardiac transplantation.

The in vitro cytotoxic reactivity of allograft infiltrating cells cultured from endomyocardial biopsies was tested against endothelial cells (EC) isolated from the own donor heart. EC derived from pieces of atrium were found to be proper targets for graft infiltrating cytotoxic T cells from four patients. The specificity of this cytotoxicity was further analysed by cold target inhibition studies and blocking with anti-CD3, anti-CD4 or anti-CD8 monoclonal antibodies. The experiments revealed that, besides a clearly HLA directed recognition, a more heterogeneous, multispecific response can be found, which might be partially explained by the activity of EC specific T cell clones. We conclude that this system provides a valuable approach to investigate the reactivity of graft infiltrating cells against EC in relation to the clinical course of the transplantation.

Antibodies, Monoclonal↗
PubMed1993

Altered specificity of alloreactive cardiac graft-infiltrating cells by prophylactic treatment with OKT3 or horse antilymphocyte globulin.

Graft-infiltrating lymphocytes from patients who were prophylactically treated with OKT3 or horse antilymphocyte globulin (H-ALG) were found to have different specificity patterns from those in the control group that received cyclosporine from the day of transplantation. This prophylactic treatment led to a significant decrease of the HLA-DR-directed cytotoxicity, while the cytolytic response against HLA-class I mismatches was hardly affected. In H-ALG patients without rejection, the percentages of class I-reactive cultures were found to be lower than in the other treatment groups, which was mainly due to a lower percentage of HLA-B--reactive cultures. In CsA and OKT3 patients, cytotoxic T cells were rather directed to HLA-B mismatches than to HLA-A antigens, while in H-ALG patients no difference in HLA-A and B-directed cytotoxicity was found. Our data suggest that OKT3 and H-ALG influence the specificity of the T cell allorepertoire, resulting in a decreased frequency of class II-specific cytotoxic T cells after transplantation. H-ALG also has a downregulating influence on the CTL response against HLA class I (HLA-B) antigens. In some patients a fast regeneration of these cells occurs, which results in a higher rejection incidence during the first posttransplant year.

Antilymphocyte Serum↗
PubMed1993

The detection of cytotoxic T cells with high-affinity receptors for donor antigens in the transplanted heart as a prognostic factor for graft rejection.

Alloreactive T lymphocytes are the initiators and effectors of acute rejection of organ transplants, and T cells with high-affinity receptors for antigen might be especially implicated in this process. It has been shown that the cytotoxic capacity of CTL with low affinity for alloantigens can be inhibited with CD8 mAb, while high-affinity CTL are not affected. To investigate whether the presence of such high-affinity cells in human heart transplants may be predictive for acute rejection, we analyzed their frequency in cultures derived from endomyocardial biopsies in 19 patients, 9 of whom had never experienced acute rejection and 10 who had had one or more rejection episodes. IN the rejectors, already before histological signs of rejection (myocyte damage) had developed, significantly higher donor-reactive CTL frequencies were found compared with the nonrejectors (medians of 10,586 vs 1,169 reactive cells per 10(6) tested cells, P = 0.002). After CD8 inhibition, the difference between rejectors and nonrejectors was even more pronounced (P < 0.001). In patients with rejection, the number of CD8-resistant, high-affinity CTL was higher than 1000 per million cells in all cases, while in patients who had never experienced rejection this number was less than 1000. As these CTL characteristics are already present before the first histological signs of rejection have developed, this might be used as a prognostic factors.

Antibodies, Monoclonal↗
PubMed1992

Polyclonal versus monoclonal rejection prophylaxis after heart transplantation: a randomised study.

Recent studies comparing the effects of induction therapy with polyclonal antilymphocyte globulins (ALG) or with monoclonal T-cell-specific antibodies are not unanimous. Therefore, 55 heart recipients were allocated to either 7-day courses of polyclonal ALG (n = 28) or of monoclonal OKT3 (n = 27). Additionally, azathioprine and low dose steroids were given. There were no severe side effects after OKT3; the course of ALG, however, had to be discontinued in 20 patients because of extensive flares. No differences between the two groups were found in freedom from rejection or in the incidence of infection. The 1- and 2-year survival was 96% in both groups. Although monoclonal and polyclonal induction therapies are equally effective for rejection prophylaxis, OKT3 may be preferred because of a lack of important side effects. However, the fact that a shorter course of ALG is equally effective may be in favour of ALG.

Adolescent↗
PubMed1992

Lysis of heart endothelial cells from donor origin by cardiac graft infiltrating cells.

Endothelial cells may be involved in the acute rejection of allografts. In the present study, graft infiltrating lymphoid cell lines were propagated from a heart graft at the time of histological diagnosis of rejection. The cell lines containing CD8+ cells lysed donor-derived BLCL and endothelial cells (EC) but not third party BLCL or random EC, suggesting that HLA antigens were recognized. The cell lines containing CD4+ cells only did not lyse any target cells. The lysis of EC without preincubation with gamma interferon (gIFN) indicated that the HLA antigens recognized were class I antigens. These results suggested that lysis of donor EC may be one of the mechanisms involved in rejection.

CD4-Positive T-Lymphocytes↗
PubMed1992

Donor directed cytotoxicity of cardiac graft infiltrating cells during cytomegalovirus infection.

We investigated whether cytomegalovirus (CMV) infection had an effect on donor directed cytotoxicity of cardiac graft infiltrating cells. The group we studied comprised 89 heart transplant recipients. Thirty eight showed signs of CMV infection, and in 27 of them cytolytic activity of biopsy-derived cultures could be tested during the infection. Fifty-one patients had never had CMV infection, and they were used as the control group. Eight patients had a primary, and 19 a secondary infection. We found that during CMV infection, both primary and secondary, a significantly higher proportion of the biopsy-derived cultures showed cytotoxicity against donor antigens (P < 0.01 when compared to the control group). In secondary infections, this was only due to an increase in donor class I directed cytotoxicity, while in primary infections a significant increase of class II directed cytotoxicity was also found (P < 0.005 when compared to secondary infection).

Cell Culture Techniques↗
PubMed1992

The influence of HLA-mismatches on phenotypic and functional characteristics of graft infiltrating lymphocytes after heart transplantation.

We studied the influence of HLA mismatches on T lymphocyte cultures that were derived from endomyocardial biopsies (EMB) from 118 heart transplant recipients. From patients with DR mismatches, the majority of the EMB-derived cultures were dominated by CD4, while in patients without DR mismatches, CD8 was the predominant T cell subset. The majority (75%) of the cultures were cytotoxic against donor antigens. A significantly (P < 0.005) lower proportion of the cultures showed cytotoxicity (36%) against HLA-A antigens when compared to HLA-B (53%) or HLA-DR (49%). A dose effect phenomenon was detected for all HLA antigens, including HLA-A: a higher number of A, B or DR mismatches resulted in a higher number of cytotoxic cultures directed against these antigens. B and DR matching had the greatest influence on 6 month freedom from rejection. Both our experimental and clinical data indicated that HLA matching played a role in the immune response against a transplanted heart.

Biopsy↗
PubMed1992

Phenotype of endomyocardial biopsy-derived T-lymphocyte cultures and chronic rejection after heart transplantation.

Chronic rejection (CR) is a major problem in long-term survival in heart transplantation. We analysed whether the occurrence of CR correlates with the incidence of acute rejections (AR) or with characteristics of endomyocardial biopsy-derived cell cultures. CR was diagnosed by annual angiography and defined as all coronary vascular changes. One year after transplantation 24 of the 63 patients had CR (38%). The incidence of AR in CR+ and CR- patients was comparable. The patients in both groups had similar individual median percentages of EMB-yielding cell cultures. During the first year the CR- patients had more cultures in which at least 60% of the cells were CD4+ T cells (50% vs 37%, P = 0.05), due to a stronger CD4 predominance in the first 6 months. In the second year the CD4 predominance in the patients diagnosed as CR+ after 1 year tended to be higher (P = 0.08). The patients had comparable percentages of cultures predominated by CD8+ T cells, gammadelta T cells or NK cells, irrespective of the time interval. These results might indicate that CD4+ T lymphocytes play a dual role in the aetiology of CR.

Adult↗
PubMed1992

Occurrence of lymphoproliferative disorder after heart transplantation is related to the total immunosuppressive load.

Heart transplant recipients are at a high risk for the development of post-transplant lymphoproliferative disorders (PTLD). We explored the relationship between the incidence of PTLD and the immunosuppressive therapy in 150 consecutive patients who received a cardiac transplant at our centre. None of our patients treated with cyclosporin A and prednisone only (n = 41) developed PTLD. In contrast, 6 of 101 patients who were previously treated with anti-T-cell preparations suffered from PTLD. No relationship was found between the type of anti-T-cell therapy and the incidence of PTLD. We conclude that the high incidence of PTLD in heart transplant recipients is related to the total immunosuppressive load and not related to a single agent like OKT3.

Drug Therapy, Combination↗