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Biomedical subjects

A M Kootte

Publications and source records attributed to A M Kootte.

At least 19 recordsLinked to original sources
PubMed1991

On a possible protective effect of HLA-A11 against skin cancer and keratotic skin lesions in renal transplant recipients.

Renal transplant recipients who have skin cancer potentially related to human papillomavirus were HLA typed with a special focus on HLA-A11, which in nonimmunosuppressed patients is negatively associated with the occurrence of virus-related carcinoma of the cervix. We found also a negative association between HLA-A11 and skin cancer; none of the 66 transplant recipients with skin cancer were positive for HLA-A11. As HLA-A11 seems to have a protective effect against skin cancer, we speculate that antigens induced by squamous cell carcinomas and possibly also by human papillomavirus may be efficiently presented through HLA-A11 to cytotoxic T cells. We also investigated a possible influence of other HLA alleles on the susceptibility of renal transplant recipients to skin cancer. The frequency of HLA-B27 was significantly higher in the transplant recipients with skin cancer, with a relative risk of 3.4 relative to healthy controls. No significant differences were found for other HLA class I or class II antigens.

Alleles↗
PubMed1990

Incidence of skin cancer after renal transplantation in The Netherlands.

The incidence of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) was analyzed separately in all 764 patients who received a renal allograft between 1966 and 1988 at the Leiden University Hospital. The mean follow-up period was 8.7 posttransplant years (range 1-21 years). During this time period 176 skin cancers were diagnosed in 47 patients. The overall risk to develop a first tumor increased from 10% after 10 years to 40% after 20 years of graft survival. The overall incidence of SCC was 250 times higher and that of BCC 10 times higher when compared with the general Dutch population. Moreover the localization of SCCs and BCCs differed considerably. Solar radiation is thought to be an important risk factor for the development of skin cancer. However, the occurrence of skin cancer in long-term graft survivors forms also a major problem in a country with a higher geographical latitude and a moderate amount of sun-exposure, such as the Netherlands.

Adolescent↗
PubMed1989

Infections in renal transplant patients treated with cyclosporine or azathioprine.

The incidence and severity of infectious complications were retrospectively investigated in 80 renal transplant patients who had been selected randomly to receive either cyclosporine (CsA) or azathioprine (Aza) in combination with low doses of corticosteroids. In the first 3 months, the incidence of infections was twice as high in the Aza-treated patients (p less than 0.05) which was due to an increase of predominantly minor infections. This increased incidence of infections was related to the increased number of anti-rejection treatments in the Aza-treated group. The types of infections were not different between the 2 treatment groups nor did the incidence of CMV infections differ. In the CsA-treated group, patients were randomly assigned at 3 months after transplantation to either continuation of CsA therapy or conversion to Aza. After conversion a small but not significant increase in predominantly minor infections was observed, which may be attributable to increased doses of corticosteroids given during the conversion. We conclude that in the first 3 months following transplantation, CsA therapy is associated with significantly less infections than Aza therapy; following conversion of CsA to Aza at 3 months only a small increase in the infection incidence is found.

Azathioprine↗
PubMed1988

Comparison of the staining of peripheral blood T lymphocytes by various anti-CD8 and HLA-DR monoclonal antibodies.

T cell subset analysis with monoclonal antibodies is performed in variety of clinical situations, including the monitoring of transplant recipients. We compared the percentages CD8+ cells in the peripheral blood of ten normal volunteers and 26 renal transplant patients using fluorescein isothiocyanate (FITC)- or phycoerytrin (PE)-conjugated Leu2a and Leu2b monoclonal antibodies (mAb). Furthermore, the percentage of HLA-DR+ cells within this population was determined using two anti-HLA-DR antibodies of differing isotype (designated 203 and 243) and either an FITC or a PE label. For both controls and transplant recipients, the PE-conjugated Leu2a and Leu2b mAbs gave significantly higher percentages of positive cells than the FITC-conjugated antibodies (P less than 0.01). Furthermore, the percentage of Leu2b+ cells was higher than the percentage of Leu2a+ cells, irrespective of the fluorochrome used (P less than 0.01); this was particularly true for samples with less than or equal to 10% Leu2a+ cells. Cell sorting experiments indicated that up to 30% of the Leu2a- population were able to bind OKT8 or Leu2b mAb in blood samples with a low percentage of Leu2a+ cells. The percentage of Leu2+ cells that were stained with anti-HLA-DR mAb 203 or 243 varied considerably, depending on the fluorochrome and the isotype of the antibodies. We conclude that the analysis of peripheral blood T cells with mAbs that apparently have the same specificity may give significantly different results, depending on the patient population, the fluorochrome and the isotype of the antibodies.

Adult↗
PubMed1988

High- and low-dose regimens of cyclosporin in renal transplantation: immunosuppressive efficacy and side-effects.

The immunosuppressive effectiveness and nephrotoxic side-effects of either high-dose cyclosporin (CsA) (16 mg/kg per day) or low-dose (9 mg/kg per day) in combination with azathioprine (Aza) (1 mg/kg per day) were studied in 80 renal transplant patients who also received low-dose corticosteroids. At 3 months, patients who received high-dose CsA were randomly assigned to either continuation of CsA or conversion to Aza, whereas in the triple-therapy group either CsA or Aza was discontinued. No differences in patient (97.5%) or graft survival (90%-92.5%) were found at 1 year. There were no differences in the incidence of primary non-functioning kidneys. The incidence of acute rejection episodes was 45% in the high-dose CsA group and 55% in the group treated with low CsA doses together with Aza (not significant). At 3 months the mean creatinine clearance was 60 +/- 4 ml/min (mean +/- SEM) in the high-dose group (mean cumulative CsA dose 0.96 g/kg) compared with 55 +/- 3 ml/min in the low-dose group (mean cumulative CsA dose 0.60 g/kg). At 1 year no differences in the degree of proteinuria or the incidence of hypertension was found between the different groups. The best mean creatinine clearance at 1 year (77 +/- 5 ml/min) was found in patients who received high doses of CsA for 3 months followed by conversion.

Adult↗
PubMed1988

Enumeration of Leu2a+, Leu2a+-DR+, and Leu2a+-Leu15+ cells in peripheral blood of renal transplant patients.

Immunological monitoring of peripheral blood cells of renal transplant patients may be helpful for diagnostic and prognostic purposes. We therefore enumerated the percentage of Leu2a+ cells as well as the occurrence of HLA-DR activation markers within this population. Since Leu2a+Leu15+ lymphocytes display suppressor functions in-vitro, this population was included in the study. Blood samples of 50 renal transplant patients within 3 months of transplantation and 41 pretransplant samples were investigated. As controls, peripheral blood cells from 10 healthy volunteers and 20 renal transplant patients with stable graft function more than 6 months after transplantation were examined. Just prior to transplantation the percentages of Leu2a+ cells, as well as the percentages of Leu15+ and DR+ cells within this population, varied considerably. Shortly after transplantation, clinical rejection episodes and cytomegalovirus (CMV) infections correlated with decreased percentages of Leu2a+ cells (P = 0.024 and 0.016, respectively). In nine patients with a decreased percentage of Leu2a+ cells shortly after transplantation but no rejection, the percentage of Leu2a+ cells normalized within 14 days. No correlation was found between increased percentages of Leu15+ or DR+ cells and rejection episodes, although the percentages of Leu2a+Leu15+ and Leu2a+DR+ cells increased significantly shortly before rejection (P less than 0.005). A decreased percentage of Leu2a+ cells, together with increased percentages of Leu15+ and DR+ cells, was seen in association with CMV infections (P less than 0.005). From this study we conclude that low percentages of Leu2a+ cells correlate with rejection episodes or CMV infections, whereas low percentages together with increased percentages of Leu2a+DR+ and Leu2a+Leu15+ cells are associated with CMV infections, especially in patients treated with high doses of cyclosporine.

Adult↗
PubMed1988

Controlled cyclosporine conversion at three months after renal transplantation. Long-term results.

The long-term results of conversion of cyclosporine to azathioprine and those of continuous CsA therapy were evaluated in a prospective study of 66 renal transplant patients who had been randomly assigned to each treatment group at 3 months following transplantation. The start point of the study was thus at 3 months posttransplant; no differences in the three-year patient and graft survival were found; these consisted of 97% and 94% in the converted group and 100% and 94% in the nonconverted group, respectively. The incidence of one or more antirejection treatments did not differ between the two groups at 3-12 months (16% vs. 17%) or after 12 months (12% vs. 9%). The incidence of hypertension at different intervals ranged from 79% to 100% in the group on continuous CsA therapy versus 50 to 58% in the converted patients. The degree of proteinuria in the 2 groups was not different at at 12 months. At 24 and 36 months the proteinuria (g/24 hr) was higher in the converted group (0.51 +/- 0.18 and 0.53 +/- 0.13; mean +/- SEM) versus the CsA group (0.15 +/- 0.04 and 0.21 +/- 0.09). At 3 years, the mean creatinine clearance for the patients converted to Aza was higher than that found for the continuously CsA-treated patients (67 +/- 8 and 59 +/- 6 ml/min; mean +/- SEM). This study shows that early CsA conversion to Aza gives a slightly better 3-year graft function, although not significantly different, compared with continuous CsA therapy without differences in patient or graft survival.

Azathioprine↗
PubMed1987

T-cell prolymphocytic leukemia with an unusual phenotype CD4+ CD8+.

A patient with T-cell prolymphocytic leukemia (T-PLL) is described. The outcome was poor, with death 8 months after diagnosis, despite several therapeutic interventions. The cells carried both CD4 and CD8 epitopes, but other thymocytic markers were absent. The spleen showed infiltration of CD4+ CD8+ prolymphocytes in the red pulp and in T-cell-dependent areas of the white pulp. Immunologic function studies revealed proliferation after stimulation with mitogens and even several antigens. However, in the mixed lymphocyte culture the T-PLL cells did not proliferate. Cytotoxic T-cells could not be induced. In T-non-T recombination experiments neither helper nor suppressor cell function was found for pokeweed mitogen-dependent plasmablast generation of normal B-cells. Cytogenetically, many abnormalities were found. Among them, 14q+; absence of chromosomes 8, 11, and 22; and the presence of large marker chromosomes and fragments.

Aged↗
PubMed1986

Acute myelocytic leukemia with acute aortic occlusion as presenting symptom.

In a 42-year-old Caucasian female, acute myelocytic leukemia (M2) presented as occlusion of the distal aorta and right iliac artery. She died after 10 days of respiratory failure. At postmortem examination the aortic wall contained multiple thrombi composed of fibrin and leukemic cells. There was no evidence of diffuse intravascular coagulation. Thromboplastic activity of the blast cells could have played a role in the formation of thrombi in the large vessels of this patient.

Acute Disease↗