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Purpose: To establish a transborder virtual tumor board (VTB) fostering state-of-the-art management of cancer patients by exchanging knowledge and expertise among oncologists in Central and Southeastern Europe (CEE)., Methods: We established and implemented a VTB based on the WebEx platform. This allowed for password-protected and secure upload of patient cases to be presented and discussed among colleagues from various oncology centers scattered throughout CEE in order to arrive at a recommendation for further diagnoses and/or treatment., Results: A total of 73 cases from 16 oncology centers located in 11 CEE countries were uploaded by 22 physicians; 71 were discussed over the course of 17 virtual meetings between June 2018 and May 2019 and 12 different kinds of malignant diseases were discussed with lung cancer (46.6%), melanoma (19.2%) and bladder cancer (13.6%) being the most commonly presented tumor entities. Of the discussed patients, 93.3% had stage IV disease at the time of presentation, 62.6% received chemotherapy or targeted treatment and 67.1% were treated with immune checkpoint inhibitors (ICPIs). The most common causes for presentation and discussion of patient cases were related to the use of ICPIs (80%)., Conclusion: When the need for expertise exceeds locally available resources, web-based VTBs provide a feasible way to discuss patient cases and arrive at conclusions regarding diagnoses and/or treatment across large geographic distances. Moreover, VTBs provide an innovative way for proper, state-of-the-art management of patients with malignant diseases in times of social distancing and the resulting need for restricted interaction during the current SARS-CoV‑2 (severe acute respiratory syndrome coronavirus type 2) pandemic., (© 2022. The Author(s).)

T cell activation initiates protective adaptive immunity, but counterbalancing mechanisms are critical to prevent overshooting responses and to maintain immune homeostasis. The CARD11-BCL10-MALT1 (CBM) complex bridges T cell receptor engagement to NF-κB signaling and MALT1 protease activation. Here, we show that ABIN-1 is modulating the suppressive function of A20 in T cells. Using quantitative mass spectrometry, we identified ABIN-1 as an interactor of the CBM signalosome in activated T cells. A20 and ABIN-1 counteract inducible activation of human primary CD4 and Jurkat T cells. While A20 overexpression is able to silence CBM complex-triggered NF-κB and MALT1 protease activation independent of ABIN-1, the negative regulatory function of ABIN-1 depends on A20. The suppressive function of A20 in T cells relies on ubiquitin binding through the C-terminal zinc finger (ZnF)4/7 motifs, but does not involve the deubiquitinating activity of the OTU domain. Our mechanistic studies reveal that the A20/ABIN-1 module is recruited to the CBM complex via A20 ZnF4/7 and that proteasomal degradation of A20 and ABIN-1 releases the CBM complex from the negative impact of both regulators. Ubiquitin binding to A20 ZnF4/7 promotes destructive K48-polyubiquitination to itself and to ABIN-1. Further, after prolonged T cell stimulation, ABIN-1 antagonizes MALT1-catalyzed cleavage of re-synthesized A20 and thereby diminishes sustained CBM complex signaling. Taken together, interdependent post-translational mechanisms are tightly controlling expression and activity of the A20/ABIN-1 silencing module and the cooperative action of both negative regulators is critical to balance CBM complex signaling and T cell activation., (© 2022. The Author(s).)

In 2008 the Ludwig Boltzmann Cluster Oncology (LBC ONC) was established on the basis of two previous Ludwig Boltzmann Institutes working in the field of hematology and cancer research. The general aim of the LBC ONC is to improve treatment of hematopoietic neoplasms by eradicating cancer-initiating and disease-propagating cells, also known as leukemic stem cells (LSC) in the context of leukemia. In a first phase, the LBC ONC characterized the phenotype and molecular aberration profiles of LSC in various malignancies. The LSC phenotypes were established in acute and chronic myeloid leukemia, in acute lymphoblastic leukemia and in chronic lymphocytic leukemia. In addition, the concept of preleukemic (premalignant) neoplastic stem cells (pre-L-NSC) was coined by the LBC ONC and was tested in myelodysplastic syndromes and myeloproliferative neoplasms. Phenotypic characterization of LSC provided a solid basis for their purification and for the characterization of specific target expression profiles. In a second phase, molecular markers and targets were validated. This second phase is ongoing and should result in the development of new diagnostics parameters and novel, more effective, LSC-eradicating, treatment strategies; however, many issues still remain to be solved, such as sub-clonal evolution, LSC niche interactions, immunologic control of LSC, and LSC resistance. In the forthcoming years, the LBC ONC will concentrate on developing LSC-eradicating strategies, with special focus on LSC resistance, precision medicine and translation of LSC-eradicating concepts into clinical application.

Immunotherapy by checkpoint inhibition is about to profoundly change cancer therapy. The number of indications are growing at an unprecedented speed. Clinical studies have demonstrated efficacy in a variety of solid tumors and in hematologic malignancies, although some clinical trials have produced negative results. Thus, it is fair to assume that there are obvious limitations and pitfalls in immunotherapy. Future concepts for combination treatment of immune checkpoint inhibitors have to be developed, but there is also urgent need for better and standardized biomarkers to identify those cancer patients who will benefit from treatment by checkpoint inhibition. The current overview summarizes current knowledge on immune checkpoint inhibitor treatment in malignancies, its outlook and limitations, diagnostic means and, finally, side effect management.

Although the precision and reliability of response time (RT) measurements performed via Web-based interfaces have been evaluated, sequences of keystrokes have never been investigated in detail. Keystrokes often occur in much more rapid succession than RTs, and operating systems may interpret successive or concomitant keyboard events according to both automatic and user-based settings. Sequence keystroke timing could thus be more sensitive than single RTs to noise in online measurements. Here, we quantified the precision and reliability of timing measures performed during sequences of keystrokes. We used the JavaScript jsPsych library to create an experiment involving finger-movement sequences, and ran it online with 633 participants. We manipulated the structure of three keystroke motor sequences, targeting a replication of previous findings regarding both RTs and interkeystroke intervals (IKIs). Our online data accurately reproduced the original results and allowed for a novel assessment of demographic variables such as age and gender. In parallel, we also measured the objective timing accuracy of the jsPsych interface by using specialized hardware and software, showing a constant 60-ms delay for RTs and a 0-ms delay for IKIs across the sequences. The distribution of IKIs revealed quantizing for a majority of participants, most likely due to the sampling frequency of their USB keyboards. Overall, these findings indicate that JsPsych provides good reliability and accuracy in sequence keystroke timings for mental chronometry purposes, through online recordings.

Bisphosphonates have been a mainstay in the treatment of cancer-related bone disease and have greatly reduced the risk of skeletal complications. More recently, clinical studies suggested additional benefits of denosumab over zoledronic acid in the prevention of skeletal related events. Similar adverse event profiles have been reported for bisphosphonates and denosumab, with infrequent occurrences of osteonecrosis of the jaw with both agents, higher incidence of renal deterioration with zoledronic acid, and higher incidence of hypocalcaemia with denosumab. Based on current evidence, the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines do not recommend one drug class over the other in patients with metastatic bone disease. Denosumab, however, may present advantages over bisphosphonates in patients suffering from chronic renal insufficiency. Further research and growing clinical experience will refine the evidence based on which decisions in daily clinical practice can be taken.

Biological features of tumor cells relevant to progression, metastasis, and prognosis in cancer patients have been investigated for many years. During the past few years, the concept of tumor stem cells has gained widespread acceptance. The cancer stem cell (CSC) model is based on the observation that continuous growth of tumors depends on a small population of immature neoplastic cells with unlimited proliferative potential. In contrast to these CSC, more mature clonal cells in the same neoplasm undergo apoptosis and die after a variable number of cell divisions. The self-renewal capacity of CSC plays a central role in this scenario and enables permanent tumor cell repopulation in vivo in patients as well as in experimental animals, e.g., immunodeficient mice. Based on the stem cell concept, it is clear that the success of an anti-neoplastic approach depends on efficient targeting and elimination of CSC. An important aspect of CSC is their intrinsic resistance against conventional drugs. Therefore, a major focus in current research is molecular targets and their expression in CSC, with the goal to use targeted drugs for CSC elimination. It is the hope for the future that therapeutic approaches involving CSC-targeting concepts will lead to sustained remission and thus improvement of prognosis in leukemia and cancer patients.

The "International Summer School on Experimental and Clinical Oncology for Medical Students" is organised at the Medical University of Vienna to teach a multidisciplinary approach to oncology to medical students in the final phase of their studies. The program includes biology, diagnosis, clinical and psycho-oncology. Lectures are given by medical, radiation and surgical oncologists. Teaching includes case reports, poster presentations and role-play. As part of the organising committee, Austrian students organise a social program. Since 1999, six courses have been held (147 students from 19 countries). Students recorded high satisfaction with organisation, scientific content and topic range. Case presentations, poster presentations and role-play were very useful. Early criticism that the program was too intense (long lectures and little interaction) has been answered. The summer school has a high degree of acceptance and is a very useful tool to teach medical students about oncology and approaching a cancer patient.

Purpose: To investigate survival of breast cancer patients by 1) age, 2) tumor stage and 3) period of diagnosis, also to determine the contribution of improvements in treatment and opportunistic mammography screening in Austria., Methods: Survival was calculated overall and by 1) age groups (in years) < 50, 50-64, > 65; 2) stage I, II, IV, unknown 3) for 17,025 patients diagnosed 1988-92, compared with 19,284 patients diagnosed 1993-97. Odds ratios for being diagnosed as stage I in the period 1993-97 compared to 1988-92 were calculated by age group and for all ages., Results: In the later period (1993-97) age-adjusted mortality rate decreased overall by 3.3% (age: < 50; 8.2%, 50-64; 5.1%, > 65; 1.6%). Overall, stage I cases increased from 46.5% to 51%. Five year relative survival rates improved significantly overall, 6.7% (p < 0.001), and within age groups (age: < 50; 4.5% (p < 0.05), 50-64; 7.2% (p < 0.05) and > 65; 7.3% (p < 0.001). This improvement is confined to patients with stage I tumors in age groups 50-64 (4.1%, p < 0.05) and > 65 (7.2%, p < 0.001) and to patients with stage II in age groups < 50 (7.7%, p < 0.01) and 50-64 (8.3%, p < 0.01). For patients younger than 50, in stage IV, diagnosed 1993-97, survival was significantly poorer (-16.9%, p < 0.05) compared to 1988-92. The odds ratio of being diagnosed as stage I in the later period was 1.19 (95% CI: 1.14, 1.24) for all ages, 1.13 (95% CI: 1.03, 1.24) and for women < 50, 1.3 (95% CI: 1.20, 1.40) 50-64 and 1.15 (95% CI: 1.09, 1.22) > 65 years old., Conclusion: We conclude that treatment improvements, which are accessible to all patients countrywide due to the compulsory state insurance system, had a major impact on positive trends in mortality and survival. Opportunistic screening should have contributed to some extent beginning in the early nineties.

Background: Medical information to oncologic patients about their disease as well as regularly updated information about the course of their disease and the therapeutic success are essential components of a comprehensive treatment in cancer patients., Study Goal: The quality of the patient-doctor-interaction as well as the hospital preference of oncologic patients were evaluated by a questionnaire at the Oncologic Out-Patient Clinic of the University Hospital of Vienna., Methods: 350 questionnaires containing 12 questions about medical information, anti-cancer therapy, suggestions for improvement and hospital preference were distributed. The questions were correlated with the patients' demographic and medical data., Results: Out of 350 questionnaires, 234 (67%)--160 (68%) by women and 74 (32%) by men--were returned. 75% of the patients were satisfied with the provided medical information. In contrast, 12% of patients felt incompletely informed about their particular cancer and 19% were unsatisfied with their state of information about the actual status of their disease. Our institution was mostly visited for quality-associated reasons and only in 3% for pragmatic reasons. 58% of the patients had no suggestions for improvement of medical care, although 28% of the patients wanted to spend more time with their doctors, 10% asked for more psychological care and 8% for additional alternative therapeutic modalities., Conclusion: The Oncologic Out-Patient Clinic is frequented mainly for quality-associated reasons. Although satisfaction with medical management is very high, there remains space for improvement of information about the underlying disease and its current status.

Purpose: Glutathione has been shown to be an effective chemoprotector against cisplatin-induced side effects in patients with ovarian cancer. In view of this fact, we performed a randomized clinical pilot-trial in the management of other solid tumors in order to compare application of Glutathione to intensive hydration in patients undergoing chemotherapy with a regimen including cisplatin., Patients and Methods: Twenty patients suffering from advanced non small cell lung cancer (n = 6) or head- and neck cancer (n = 14) were enrolled in the study. All patients received 80 mg/m2 cisplatin along with etoposide or 5-fluorouracil every 4 weeks. Patients randomized to application of Glutathione (n = 11) received 5 g of Glutathione immediately before application of cisplatin followed by 2000 ml of normal saline. Patients in the control group (n = 9) received 2000 ml electrolyte infusion before and 2000 ml of normal saline with forced diuresis after cisplatin., Results: The intensity of hematologic toxicity was significantly less pronounced in patients treated with Glutathione than in the control group (hemoglobin: 10.7 vs 9.5 mg% respectively, p = 0.039; white blood cell count 3.3 vs 2.2 x 103/microliter respectively, p = 0.004; platelets 167 vs 95 x 103/microliter respectively, p = 0.02), whereas in terms of non-hematologic toxicity no difference was observed. Objective remission occurred in 6 out of 11 evaluable patients from the group receiving Glutathione (55%; complete remission: 9%; partial remission: 46%), and in 4 out of 8 evaluable patients from the control group (partial remission: 50%). However, there was no statistical difference in terms of response and overall survival (13.5 months vs. 10.5 months) between the two groups., Conclusions: Application of Cisplatin and Glutathione seems to be safe and feasible and the antitumoral efficacy of cisplatin is apparently not impaired by the concomitant use of Glutathione in patients with solid tumors.

Informed consent is currently an ethical, medical and legal requirement. Increasing public discussion concerning real or supposed malpractice has caused patients to adopt a critical attitude and has caused courts to increasingly demand informed consent for patients. Unfortunately, the legal requirements for informed consent have developed from atypical situations involving dissatisfied and injured patients rather than from the more common occurrence of physicians helping patients and having satisfied patients. In addition, the law has failed to establish explicit guidelines for physicians. We review the elements of informed consent based on current Austrian and German jurisdiction in the particular field of oncology and summarise the legal and medical realities with the aim of delineating specific criteria for decision making.

Adhesion molecules are membrane proteins responsible for the complex functions of cell adhesion and cellular recognition and are thus of importance in inflammatory as well as neoplastic diseases. Adhesion molecules seem to play a significant role at each level of the metastatic cascade, including the destruction of normal cell-cell as well as cell-substrate cohesion, the penetration of tumor cells into the vascular system and the further spread into distant organs. In this summary an overview of subtypes, structure and function of the major groups of adhesion molecules is given and their possible role in the development, propagation and metastatic spread of malignancies discussed. Cell adhesion and its defects may be of importance in the behaviour of tumor cells and their spread. A better understanding of their function and possible manipulation of their expression, e.g., by cytokines could provide new therapeutic approaches in clinical oncology.

A survey of clinical data shows that substitution with intravenous immunoglobulins constitutes an essential further step in the therapy of patients with immunodeficiencies: patients with primary and some secondary immunodeficiencies clearly benefit from intravenous immunoglobulin substitution. Some other diseases including idiopathic thrombocytopenic purpura and the Kawasaki syndrome also constitute indications for this kind of treatment. In other cases (infections in newborn preterm infants, children with AIDS, chronic inflammatory demyelinizing polyneuropathies and the Guillain-Barré syndrome and children with refractory seizures) there are reasons to believe that intravenous immunoglobulin therapy can be of benefit, although bigger controlled studies are still necessary to allow definitive conclusions to be reached. Further attempts will have to be made to improve understanding of the mode of action of intravenously administered immunoglobulin.

An overview has been attempted of the internal complications, including infections, malignancies and other HIV-associated diseases, in patients with the acquired immune deficiency syndrome (AIDS) and a comparison made between international data and our own experience in Austria. Moreover, the current therapeutic options of opportunistic infections and malignancies, their results and complications are given. Although the number of patients with AIDS in Austria is still relatively small and conclusions can be drawn only with caution, it seemed that our patients differed from international statistics not only concerning their distribution within the defined risk groups, but also with regard to the occurrence of infections and other diseases. The present analysis has to be viewed, therefore, as only an interim report of the internal manifestations of AIDS in patients from Austria until the data from larger numbers of patients are available.

This study presents a report on the first clinical experiences gained in 68 hospitalized HIV antibody-positive patients from Austria, covering a period of twelve months. 36 patients (52.9%) belonged to risk group I or Ib (homo- or bisexual), whereas 26 (38.2%) patients were i.v. drug abusers (risk group II). 5 (7.4%) patients fulfilled the criteria of stage II of the CDC classification of HIV-associated clinical symptoms, 10 (14.7%) were classified as stage III and the remaining 53 patients (78%) as stage IV. The most frequent and also the most serious problem was the development of opportunistic infections. Multiple infections were found in 45.7% of all cases. Kaposi's sarcoma was found in 9 patients who all belonged to risk group I. During the entire observation period 10 patients died as a consequence of HIV-1-induced immunodeficiency and the resulting opportunistic infections and/or neoplasms.

Leukocyte locomotion (LL) of 40 patients with rheumatoid arthritis (RA) was found to be unimpaired as compared to LL of 23 control individuals (p Greater Than 0.2). Casein and zymosan activated human sera were used as cytotaxins, and the sera of RA patients proved to be activatable in the same way as control sera in that they produced a similar chemotactic activity (p Greater Than 0.2). However, RA sera inhibited LL significantly (p Less Than 0.01) in comparison to control sera. This phenomenon was unchanged after elimination of immune complexes be ultracentrifugation, but could be reversed, after incubation of cells with RA sera, by reincubation with control sera.

Rabbits were injected intraarticularly three times with 0.5 ml of 10, 50 or 100 mg% purified rheumatoid synovial collagenase or with identical amounts of trypsin. 18 hours after the last injection the collagenase-injected animals showed distinct cellular exudation into the synovial fluid and acute arthritis; one week later there was a decrease of the cell count in the synovial fluid and appearance of proliferative synovitis, while 3 weeks later there was no exudation and less chronic inflammation but distinct fibrosis of the synovium. A direct action of collagenase on the connective tissue components would seem to be responsible for these changes. No pathologic alteration of the cartilage was observed. Trypsin-injected control animals showed negligible cellular exudation and no pathologic alteration of the synovium.

Human rheumatoid arthritis (RA) collagenase and bacterial collagenase were shown to agglutinate collagen-coated erythrocytes. Native collagens of type I and type II reacted equally well, while denatured collagens showed less distinct agglutination activity. The sensitivity of the method for the detection of purified bacterial collagenase from Clostridium histolyticum is very high (100 pg). It is, however, low for human RA collagenase. The agglutination reaction is not inhibited by concentrations of native collagen causing distinct inhibition of anticollagen sera (2mg%). EDTA inhibits the agglutination completely.

Based on our 14-year experience with breast-preserving treatment of breast cancer, we recommend limited surgical intervention for the removal of a small mammary carcinoma under the proviso that adequate radiotherapy is available and that the patient can be thoroughly followed up. We are convinced that the good cosmetic result and especially the excellent psychological reaction are particularly important in order that women lose their fear of an ablative operation. Only then, by performing an operation which is not excessive at the earliest possible time can the prognosis of this type of carcinoma, which is increasing be improved.

The present study aimed at elucidating lytic effector cell function in 32 schizophrenic patients and comparing the results with data obtained in 27 normal probands. Natural killer cell (NK) activity and antibody dependent cellular cytotoxicity (ADCC) were tested. Schizophrenics did not differ from normal controls in either test system. Within the schizophrenic group, higher NK activity was detected in patients with neuroleptic monotherapy (p less than 0.05). Patients given a combination of neuroleptics, antidepressants and/or lithium did not differ from drug-free patients in either test system. There was no influence of psychopathological variables on lytic effector cell function.

14 patients who underwent a standardized total hip joint replacement were investigated in order to detect postoperative impairment of chemotactic or phagocytic function of their polymorphonuclear leucocytes. A chemotaxis assay in modified Boyden [3] chambers and the nitroblue-tetrazolium assay were used. 25 healthy control persons served for the assessment of normal values and the reproducibility of the respective test. Patients were investigated preoperatively and on the first, third and sixth postoperative day. While phagocytosis remained unchanged throughout the period of investigation, chemotactic leucocyte function was regularly significantly depressed on the first postoperative day. The defect in postoperative chemotaxis might, despite of an unimpaired phagocytic capacity, contribute towards an increased risk of postoperative infections.

Three groups of rabbits were investigated: I. 9 rabbits, immunized with rabbit collagen type I, received 1 intraarticular injection of same antigen in the right knee, and control preparations in the left knee. II. 4 rabbits, immunized with calf collagen type I, received the same intraarticular injections as in group I. III. 2 non-immunized rabbits received also the same intraarticular injections. Synovial fluid and synovium were obtained in all groups 18 hours after intraarticular injection. Knee-joints of all animals immunized and challenged intraarticularly with rabbit collagen showed strong cellular exsudation (mean 1.800 X 10(3) cells,) in contrast to control joints (mean 21 to 484 X 10(3) cells). Histologic investigation of synovium of group I animals showed in rabbit collagen injected knees in contrast to controls, vascular reactions with enlargement of small vessels, thikening of endothelial cells, perivascular infiltration and aggregation of polymorphonuclears in lumen of vessels. Intraarticular injection of rabbit collagen in calf collagen immunized rabbits, induced a limited cellular exsudation, (mean 670 X 10(3) cells) which was lower than in rabbit collagen immunized animals, however also more pronounced than in control joints. Whilst results after intraarticular injection of rabbit collagen in rabbit collagen immunized animals are interpreted as early signs of autoimmune arthritis, results after intraarticular injection of rabbit collagen in calf collagen immunized animals are regarded as milder symptoms of synovitis induced by crossreactivity of antigens.

The importance of the presence of hormone receptors of cells derived from breast cancer tissue for the duration of the relapse-free interval was evaluated in 41 patients with stage II breast cancer. After modified radical mastectomy with axillary lymphadenectomy the patients received radiotherapy and adjuvant polychemotherapy and/or hormone therapy. There was no indication of metastases in any patient at the time of operation. There was a significant correlation of the relapse-free interval to tumor size (p less than 0.05), to the number of involved lymph nodes (p less than 0.0005), and also to the presence of the progesterone receptor (PgR), which seemed to play a more important role in this context than the oestrogen receptor (ER) (p less than 0.001). We conclude from this study that the evaluation of the PgR in breast cancer cells is important for the prognosis of the duration of the relapse-free interval.

Acute T-lymphocytic leukemia diagnosed in a 14-year old boy on the basis of typical cell morphology, as well as by membrane antigen analysis with monoclonal antibodies, shifted to the phenotype of an acute eosinophilic leukemia 5 months after the initiation of chemotherapy. The transformation was evident by a change in morphology of cells derived from bone marrow aspirates, by cytochemistry and by a shift in the membrane antigen pattern.

An increased incidence of infections, especially during periods of poor metabolic control is well known in patients with insulin-dependent diabetes mellitus. Therefore, we studied polymorphonuclear chemotaxis and its dependence on the degree of diabetic control in 49 patients with insulin-dependent diabetes mellitus in 46 controls. A modification of the chemotaxis assay described by Frei et al. was used as test system. The mean chemotactic activity observed in the total group of insulin-dependent diabetics did not differ from the values obtained in the controls. However, in patients with poor diabetic control and glucosuria exceeding 60 g/24h, a significantly reduced chemotactic leucoyte migration was found. These data indicate that normalization of leucotaxis can be achieved in insulin-dependent diabetes by means of adequate diabetes control.

The leucocytes of 22 patients with classic rheumatoid arthritis were investigated with the direct leucocyte migration inhibition technique in agarose as described by Clausen. The leucocytes of 9 patients with degenerative joint diseases and of 9 healthy persons served as controls. Collagen type I and collagen type III were used as antigens. The leucocytes of 22 patients with rheumatoid arthritis showed in 15 cases a migration inhibition with collagen type III and in 10 cases with collagen type I. The inhibition with collagen type III was stronger and more frequent than with collagen type I. The frequent leucocyte migration inhibition with collagen type III in classic rheumatoid arthritis seems to be an expression of possible cell mediated reactivity against that type of collagen which appears especially in rheumatoid synovial tissue.

A number of findings concerning the pathogenesis of insulin-dependent diabetes mellitus have shown that an autoimmune process is responsible for the destruction of the beta-cell mass, and that a major part of this process has already occurred during the prediabetic phase of the disease. Various immunosuppressive intervention trials have, thus, recently been performed. Remission rates of between 30% and 50% in the Canadian cyclosporin A (CyA) pilot study prompted two placebo-controlled double-blind studies applying this medication. In the French CyA trial 122 patients were followed up for 9 months. 37% of those on high-dose CyA (whole blood levels greater than 300 ng/ml) achieved total remission, compared with 16.7% of those on low-dose CyA (blood level less than 300 ng/ml) and 5% of the placebo group. The Canadian-European trial included 188 patients, of whom 42 were treated in the Viennese centre. Diabetes had been diagnosed in these 42 patients not more than 6 weeks previously, and the duration of their symptoms did not exceed 14 weeks. Whole blood CyA levels ranged from 400 to 800 ng/ml. In relation to short duration of symptoms and early commencement of treatment up to 10 times higher total remission rates were found in the CyA group as compared with the placebo group. In both studies similar side effects were seen. Apart from the cosmetic side effects (hypertrichosis, gingival hyperplasia) a decrease of 20% in creatinine clearance and an increase of 20% in plasma creatinine level seemed to be of clinical importance.(ABSTRACT TRUNCATED AT 250 WORDS)