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Medical students often lack the ability to develop strategies for problem solving based on adequate diagnostic and therapeutic measures. Case studies are an appropriate learning as well as examining tool for this purpose. For in-house examinations new computer based examinations are playing an important role, because they permit a chronological approach to clinical cases. At the same time this method allows the use of new question and answer formats. Based on this background CASUS was introduced at the Heinrich-Heine-University of Duesseldorf as a mandatory case and computer-based learning system including an online computer-based exam for the first time in Germany. About 140 students participated in the examination which was held at the university's computer centre. The introduction of the online examination led to a significant increase in the use of the CASUS study cases during the term. The study cases as well as the online examination were accepted very well among the students. Despite the cost-effective use of this multimedia method and its didactic advantages it currently requires more administrative efforts and is more interference-prone than traditional paper based examinations with multiple choice questions. Problems of justiciability and technological safety have to be solved first before a routine use in summative evaluation of learning. Therefore, at present online examinations can serve for the formative evaluation of learning. Medizinstudierenden fehlt es oftmals an der Fähigkeit, Strategien zur Lösung von Problemen mittels geeigneter diagnostischer und therapeutischer Maßnahmen zu entwickeln. Hierfür bieten sich Fallstudien als geeignetes Lern- und Prüfungsformat an. Für fakultätsinterne Prüfungen spielen neue, computerbasierte Prüfungsformate eine wichtige Rolle, da mit ihnen das chronologische Vorgehen an klinischen Fällen gut simuliert werden kann. Gleichzeitig erlaubt das Prüfungsverfahren auch den Einsatz neuer Frage- bzw. Antwortformate. Vor diesem Hintergrund wurde an der Heinrich-Heine-Universität Düsseldorf mit CASUS erstmalig in Deutschland ein fall- und computerbasiertes Lernsystem zum Lernen mit anschließender internetbasierter Online-Prüfung verbindlich eingesetzt. Die Prüfungen wurden mit ca. 140 Studierenden im Universitätsrechenzentrum durchgeführt. Mit der Einführung der Online-Prüfung stieg der Nutzungsgrad der CASUS-Lernfälle während des Semesters deutlich an. Neben den Lernfällen fand auch die Online-Prüfung eine hohe Akzeptanz bei den Studierenden. Trotz des kostengünstigen Einsatzes multimedialer Elemente und der didaktischen Vorteile der Online-Prüfung ist der administrative Aufwand momentan noch größer und die Durchführung störanfälliger als eine klassische Papierklausur mit Antwortwahlverfahren. Für summative Prüfungen müssen aktuell noch Probleme der Justiziabilität und technischen Sicherheit für den Routineeinsatz gelöst werden, weshalb sich gegenwärtig der Einsatz insbesondere für formative Prüfungen anbietet.

OBJECTIVE We related organ-specific autoantibodies, including diabetes-associated autoantibodies (DAAs) and non-DAAs to systemic cytokines/chemokines in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS From the European Action LADA (latent autoimmune diabetes in adults) cohort, patients with adult-onset type 1 diabetes (n = 80, of whom 50 had LADA and 30 had classic type 1 diabetes) and type 2 diabetes (n = 626) were analyzed for DAAs (GAD antibody [GADA], IA-2 antigen, islet cell antibody, and zinc transporter T8), non-DAAs (transglutaminase, thyroid peroxide autoantibodies, parietal cell antibodies), and 10 immune mediator concentrations (measured by LUMINEX). RESULTS Type 1 diabetes patients (whether having classic type 1 diabetes or LADA), apart from their clinical phenotype, could not be distinguished by either autoantibodies (both DAAs and non-DAAs) or immune mediators. In type 1 diabetes, most immune mediators (9 of 10) were negatively correlated with DAA titers. Type 2 diabetes patients, who by definition were without DAAs, had fewer non-DAAs (P < 0.0005), but had higher levels of proinflammatory immune mediators, especially compared with patients with type 1 diabetes who had high GADA titers (interleukin [IL]-6 [P < 0.001], soluble E-selectin [P < 0.01], and IL-1 receptor antagonist [P = 0.052], for trend). CONCLUSIONS Patients with type 1 diabetes had more DAAs and non-DAAs than did those with type 2 diabetes, whereas the frequency and nature of these autoantibodies was broadly similar in classic type 1 diabetes and LADA. Systemic immune mediator levels, in the main, were negatively correlated with DAA titers, and, for some, were higher in patients with type 2 diabetes, especially when compared with patients who had high GADA titers. Differences in the clinical classification of diabetes are associated with graded differences in adaptive and innate immune reactivity.

Background The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. Methods We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). Results The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased. Conclusions Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.)

BACKGROUND AND OBJECTIVE Type 1 diabetes is characterised by a chronic autoimmune process predominantly transmitted by T-cells. Yet current knowledge about autoimmune reactions in type 1 diabetes transmitted by antigen-specific T-cells is very limited. In this study we investigated T-cell reactivity to potential autoantigens and their immunodominant epitopes in patients with type 1 diabetes and in control groups. PATIENTS AND METHODS Using 3H-thymidine incorporation in peripheral blood lymphocytes in patients with type 1 (group 1) or type 2 (group 2) diabetes, healthy controls (group 3) and healthy twins of type 1 diabetics (group 4), cell reactivity was measured to the proteins insulin and glutamate decarboxylase (GAD) 65 and against the peptides of insulin, GAD 65, heat shock protein (HSP) and bovine serum albumin (BSA). RESULTS Patients with type 1 diabetes had a significantly higher stimulation of peripheral T-lymphocytes by GAD 65 and a mixture of selected GAD 65 peptides than healthy controls. There was no significant difference between the groups with regard to the stimulation of peripheral blood lymphocytes by insulin, individual GAD peptides or insulin, HSP- and BSA-peptides. CONCLUSIONS Autoantigen-specific T-lymphocytes can be demonstrated in blood of type 1 diabetics. The necessary tests for this are at present relatively cumbersome and therefore limited to special research laboratories. But in the future their identification in autoimmune diseases, such as type 1 diabetes, will be a valuable addition to the demonstration of antibodies in which, even in the prediabetic phase, possibly protective and cytotoxic immune reactions can be distinguished.

OBJECTIVE-Specific autoantibodies characterize type 1 diabetes in childhood but are also found in adult-onset diabetes, even when initially non-insulin requiring, e. g., with latent autoimmune diabetes (LADA). We aimed to characterize adult-onset autoimmune diabetes. RESEARCH DESIGN AND METHODS-We consecutively studied 6,156 European diabetic patients attending clinics within 5 years of diagnosis (age range, 30-70 years) examined cross-sectionally clinically and for GAD antibodies (GADA) and antibodies to insulinoma-associated antigen-2 (IA-2A) and zinc-transporter 8 (ZnT8A). RESULTS-Of 6,156 patients, 541 (8.8%) had GADA and only 57 (0.9%) IA-2A or ZnT8A alone. More autoantibody-positive than autoantibody-negative patients were younger, leaner, on insulin (49.5 vs. 13.2%), and female (P < 0.0001 for each), though LADA patients (9.7% of total) did not show categorically distinct clinical features from autoantibody-negative type 2 diabetes. Similarly, more GADA patients with high (>200 World Health Organization IU) (n = 403) compared with low (n = 138) titer were female, lean, and insulin treated (54.6 vs. 39.7%) (P < 0.02 for each). Autoantibody-positive patients usually had GADA (541 of 598; 90.5%) and had LADA more often than type 1 autoimmune diabetes (odds ratio 3.3). CONCLUSIONS-Adult-onset autoimmune diabetes emerges as a prevalent form of autoimmune diabetes. Our results indicate that adult-onset autoimmune diabetes in Europe encompasses type 1 diabetes and LADA in the same broad clinical and autoantibody-positive spectrum. At diagnosis, patients with adult-onset autoimmune diabetes are usually non-insulin requiring and clinically indistinguishable from patients with type 2 diabetes, though they tend to be younger and leaner. Onlywith screening for autoantibodies, especially GADA, can they be identified with certainty. Diabetes Care 36:908-913, 2013

Using the indirect immunofluorescence test for the detection of pituitary autoantibodies in human serum, the results obtained with human fetal and non-human pituitary antigens were compared. Of the sera that were positive on human fetal substrate, 4% were recovered with adult baboon, 0% with fetal cymologous, 20% with porcine, 11% with bovine, 11% with ovine, and 7% with rat tissue. The rate of heterophilic antibodies to the above animal substrates was 5% to 14%. In contrast to human adult pituitaries, normal human sera did not bind to Fc receptors on ACTH-cells of human fetal pituitaries. This allowed the demonstration of ACTH-cell antibodies. The specificity of the reaction was proven by absorption studies with purified Fc fragments. These results suggest that human fetal tissue is the best source of antigen for the detection of pituitary autoantibodies. The use of animal tissue including non-human primate pituitary yields results that bear no clinical significance.

While aging is known to decrease episodic thyrotropin (TSH) secretion in men, no detailed information is available as to age-related alterations in the TSH and prolactin (PRL) release patterns in postmenopausal women (PMW). Accordingly, we compared the TSH and prolactin (PRL) secretory profiles of 6 euthyroid younger PMW (mean age: 53.0 years) with those of 7 euthyroid older PMW (mean age: 80.4 years). In all PMW, blood samples were obtained at 10 minute intervals for 10 hours for serial determinations of TSH and PRL by RIA. While thyroxine (T4) serum concentrations were not different in younger from older PMW, triiodothyronine (T3) levels markedly (p less than 0.05) decreased in older PMW. In both younger and older PMW, TSH and PRL were secreted episodically (by Cluster pulse algorithm), with considerable inter-individual variabilities in either study group. TSH and PRL pulse attributes (interpulse intervals, frequencies, amplitudes) were comparable in younger and older PMW, although a tendency of mean TSH to increase (p = 0.18) was noted for older PMW. Mean TSH and PRL serum concentrations were positively (r = 0.94, p less than 0.01) correlated in older, whereas not in younger PMW. These observations demonstrate that the pulse characteristics of episodic TSH and PRL secretion are preserved in PMW even of old age. However, in view of markedly decreased circulating T3 concentrations and of no substantial change in the TSH pulsatile secretion in older PMW, the negative feedback on the hypothalamic-pituitary unit may be impaired in elderly women.