Malignant tumours after renal transplantation.

The incidence of malignant tumours in 570 patients with kidney transplants was examined. It was found to be 20-30 times higher than in the average (normal) population. In accordance with the literature, mainly skin cancers were observed, but at variance with these data, the number of lymphoreticular malignancies was small. On the basis of their study, the authors emphasize the oncogenetic effect of immunosuppression. By comparing the conventional (AZA+PRED) and Cyclosporine (CYA+PRED) treatments, they point out that this risk should be taken into consideration even in Cyclosporine therapy which has otherwise a much more favourable effect.     

Soluble CD14 but not interleukin-6 is a new marker for clinical activity in atopic dermatitis

Summary Levels of soluble IL-2 receptors, IL-6, soluble CD23, soluble CD14 and ECP (eosinophilic cationic protein) were measured as markers of T-cell, B-cell, monocyte and eosinophilic leucocyte activation in 26 patients with atopic dermatitis (AD) on admission to (A) and at discharge from (D) the Department of Dermatology in Zurich. The serum levels of sIL-2R, IL-6, sCD23, sCD14 and ECP were significantly elevated in AD patients in comparison with the normal values of healthy donors. A significant decrease in sIL-2R (p=0.0093) and in sCD14 (p=0.0134) levels was demonstrated between A and D, correlating with the improvement in the skin intensity score (SIS). In addition, a significant correlation of the sCD14 levels and the SIS at A was demonstrated (p=0.0415). These results also incriminate monocytes in the pathogenesis of AD, indicating that, besides sIL-2R and ECP, SCD14 could also be a possible marker for the disease activity.     

Iodine-125 Brachytherapy of Brain Stem Tumors

PURPOSE: To report on iodine-125 ((125)I) interstitial irradiation in the treatment of brain stem tumors. PATIENTS AND METHODS: Two patients with brain stem tumors were treated with CT- and image fusion-guided (125)I stereotactic brachytherapy. RESULTS: By March 2003, the patients had been followed up for 47 and 13 months, respectively. In case 1, the tumor volume was 1.98 cm(3) on the control CT, indicating a 65.5% shrinkage as compared to a target volume of 5.73 cm3 at the time of brachytherapy. In case 2, shrinkage was more distinct. After irradiation, the cyst volume was 0.16 cm(3) on the control MRI, indicating a 97.4% shrinkage as compared to a target volume of 6.05 cm(3) at the time of brachytherapy, i. e., the metastasis had virtually disappeared. CONCLUSION: CT- and image fusion-guided (125)I stereotactic brachytherapy can be performed during the biopsy session. The procedure can be well planned dosimetrically and is surgically precise.     

Predominance of a rare type of HIV-1 in Estonia

An earlier study has indicated that a complex recombinant HIV-1 strain dominates the epidemic in Estonia. The objective of this study was to further investigate the molecular epidemiology and genetic structure of HIV-1 in Estonia. Most of the investigated individuals became infected after August 2000 when HIV-1 started to spread rapidly among Estonian intravenous drug users (IDUs). Two viral DNA regions, gag/pol and gp41, were sequenced and subtyped from peripheral blood mononuclear cells or plasma from 141 individuals. Phylogenetic analysis in the gp41 region revealed that the most frequent type of the virus among IDUs was a circulating recombinant form, CRF06_cpx, whereas a few samples showed highest sequence similarity to a subtype A strain circulating in Ukraine and Russia. Likewise, in the gag/pol region, most of the samples were classified as CRF06_cpx, with a few classified as subtype A. In this region, however, 16% of the sequences turned out to be mosaic unique recombinant forms consisting of CRF06_cpx and subtype A. At least 9 mosaic forms were identified, each with distinct patterns of multiple crossover. To characterize Estonian CRF06_cpx as well as recombinant isolates in more detail, 4 near-full-length HIV-1 genomes were sequenced.     

Perforin dependence of natural killer cell-mediated tumor control in vivo

Adaptive immune surveillance by T cells against infections and tumors depends on the presence of antigenic peptides presented by major histocompatibility complex (MHC) molecules. If antigenic tumor-specific peptides or MHC class I molecules are absent, the adaptive T cell immune response fails. Natural killer (NK) cells seem to complement the specific T cells by recognizing target cells lacking MHC class I (e.g. RMA-S). The role of perforin, which is crucially involved in T cell and NK cell-mediated target cell lysis, was evaluated in mice lacking perforin with respect to their capacity to eliminate a syngeneic lymphoid tumor. Here, we show that growth of MHC class I^? RMA-S tumor cells in unprimed mice was controlled by NK cells through perforin-dependent cytotoxicity.     

Detection of perforin and granzyme A mRNA in infiltrating cells during infection of mice with lymphocytic choriomeningitis virus

The analysis of gene expression in cytotoxic T cells by in situ hybridization of serial liver and brain sections from mice infected with lymphocytic choriomeningitis virus (LCMV) and immunostaining with T cell marker- and virus-specific antibodies revealed a close histological association of infiltrating lymphocytes expressing the perforin and granzyme A genes with virally infected cells. Maximal frequency of perforin and granzyme A mRNA-containing cells on liver sections preceded by about 2 days maximal LCMV-specific cytotoxicity of the lymphoid liver infiltrating cells. These results are most consistent with an involvement of perforin and granzyme A in cell-mediated cytotoxicity in vivo.     

FN-C1q and C1 INH C1r-C1s complexes as indicators of complement activation in patients with chronic lymphocytic leukaemia

We have previously found low levels of C1 and C4 INH in the sera of chronic lymphocytic leukaemia (CLL) patients. Hypocomplementaemia was supposed to be the consequence of a permanent activation of the classical pathway. We have compared the levels of C1 INH-C1rC1s and C1q-FN complexes in the sera of 95 CLL patients and 100 healthy controls, because these complexes are known to be formed in the early stage of classical pathway activation. A significant increase in the level of both types of complexes was found in sera of CLL patients as compared to the controls. These findings support the assumption that the classical complement pathway is activated in the patients with CLL.     

Soluble E-selectin correlates with disease activity in cyclosporin A-treated patients with atopic dermatitis

BACKGROUND: The expression of adhesion molecules on endothelial cells regulates leukocyte migration. The level of soluble adhesion molecules which are shed into the circulation is known to reflect the degree of inflammation, and this level can therefore be used as an indicator of disease activity. The objective of this study was first to investigate the relationship between sE-selectin levels and disease activity parameters (scores of extent, severity, itch, and sleep) in atopic dermatitis (AD) patients, and second to determine the effect of therapy with an immunosuppressive drug (cyclosporin A) on sE-selectin levels. METHODS: Fourteen patients with severe AD and 41 healthy controls were studied. sE-selectin was measured by ELISA both 2 weeks before therapy with cyclosporin A and after 16 weeks of treatment. RESULTS: At baseline, the level of sE-selectin was significantly higher in patients with AD than in healthy control subjects (P<0.0001). After treatment of AD with cyclosporin A, there was a significant reduction of the sE-selectin levels (P<0.0001). In addition, changes in sE-selectin levels significantly correlated with changes in disease activity parameters such as severity (P<0.002) and extent of disease (P<0.049). CONCLUSIONS: Soluble E-selectin is a new serologic marker in AD which reflects disease activity. Therefore, soluble E-selectin may be a useful parameter in the monitoring of this disease.     

Study of completeness of registration at the Estonian cancer registry.

Every cancer registry should be able to quantify the level of completeness of registration. The current study describes a routine quality control procedure in the Estonian Cancer Registry (ECR) for assessing the completeness of registration. The registry's database was compared with the databases of the Tartu University Lung Clinic and the Maarjam?isa Hospital of the Tartu University Clinics, and active retrieval to obtain missing cancer cases diagnosed in 1998 was carried out. The overall completeness of case ascertainment based on this study was 90.8%. As a result of this procedure, 67 cases of malignant neoplasms (1.1% of the total number of incident cancer cases for 1998) and 11 cases of other reportable neoplasms were detected and recorded at the ECR. Cancers of the lung, thyroid gland and prostate were most frequently under-notified. For these sites, the number of cancer cases for 1998 for Estonia as a whole increased 2.6%, 11.8% and 2.2%, respectively. To conclude, the existence of electronic databases is a positive development, but cancer registrars still need to employ labour-intensive methods to validate diagnostic codes and to decide whether to include in the ECR cases found by active retrieval. Based on the findings of our study, which is the first one of its kind in Estonia, the completeness of cancer reporting varied by cancer site, and it appeared to be a substantial concern for several sites.