Arzneimitteltherapiesicherheit bei Kindern

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Bei Kindern und Jugendlichen treten Medikationsfehler häufiger auf als bei Erwachsenen, da die Evidenz oft fehlt und die...     

Dissociable medial frontal negativities from a common monitoring system for self- and externally caused failure of goal achievement

Goal-directed behavior requires the ability to adapt performance strategies based on the attribution of unintended outcomes to internal or external causes. Using event-related brain potentials, the present research compared neural activity following self-generated errors induced by a flanker task and following externally generated errors induced by supposed “technical malfunctions”. Errors and malfunctions were associated with temporally dissociable ERP components, the short-latency error-related negativity (ERN) and the longer-latency feedback-related negativity (FRN), respectively. Independent component analysis (ICA) was applied to compare the underlying neural components of ERN and FRN. ICA results revealed that the FRN is attributable to the neural sources of the ERN, suggesting that the two components share a source network. Furthermore, single-trial amplitudes of ERN and FRN were specifically related to the implementation of error correction and malfunction compensation: the stronger the failure signal, the more efficient was remedial behavior. Together the results demonstrate that internally and externally generated unintended action outcomes engage a common monitoring mechanism that manifests in two temporally distinct ERP components and induces similar compensatory processes. The temporal dissociation of the ERP components might provide the basis for further processes of outcome attribution underlying action selection and changes in performance strategy. In line with recent neuroimaging findings, ERN and FRN appear to reflect the use of different sources of information about action outcome to update action value.     

Clonal chromosomal aberrations in bone marrow cells of Fanconi anemia patients: gains of the chromosomal segment 3q26q29 as an adverse risk factor

Fanconi anemia (FA) is a condition that induces susceptibility to bone marrow failure, myelodysplastic syndrome (MDS), and leukemia. We report on a high incidence of expanding clonal aberrations with partial trisomies and tetrasomies of chromosome 3q in bone marrow cells of 18 of 53 FA patients analyzed, detected by conventional and molecular cytogenetics. To determine the clinical relevance of these findings, we compared the cytogenetic data, the morphologic features of the bone marrow, and the clinical course of these patients with those of 35 FA patients without clonal aberrations of 3q. The 2 groups did not differ significantly with respect to age, sex, or complementation group. There was a significant survival advantage of patients without abnormalities of chromosome 3q. Even more pronounced was the risk assessment of patients with gains of 3q material with respect to the development of morphologic MDS and acute myeloid leukemia (AML). Thus, our data from 18 patients with 3q aberrations reveal that gains of 3q are strongly associated with a poor prognosis and represent an adverse risk factor in FA.     

Antiphospholipid antibodies in pediatric and adult patients with rheumatic disease are associated with parvovirus B19 infection

OBJECTIVE: To show a possible association between parvovirus B19 infection and the presence of antiphospholipid antibodies (aPL) in patients with rheumatic diseases. METHODS: Serum samples obtained from 88 children with various forms of juvenile rheumatic disease and from 40 adults with systemic lupus erythematosus, the antiphospholipid syndrome, or other rheumatic disease, who had previously been tested and shown to be positive for IgG aPL, were analyzed for the presence of B19 DNA, for antibodies against the B19 viral proteins VP1, VP2, and NS1, and for IgG aPL (anticardiolipin, anti-beta(2)-glycoprotein I, and antiphosphatidylserine). As controls, serum samples obtained from 135 children with noninflammatory bone diseases or growth retardation were also analyzed. RESULTS: Twenty-four (27%) of the 88 children with rheumatic diseases had detectable amounts of IgG aPL. Fourteen (58%) of these 24 IgG aPL-positive patients showed IgG against VP1/VP2 and viral genomes, indicating the presence of acute (2 patients) or persistent (12 patients) infection. Past parvovirus B19 infection was identified in 7 (29%) of 24 IgG aPL-positive children, as indicated by VP1/VP2-specific IgG in the absence of viral DNA. Three (12%) of 24 IgG aPL-positive children had not been infected with B19. Sixty-nine (51%) of 135 control children displayed VP1/VP2-specific IgG. Three (2%) of these 135 children were IgG aPL positive (2 children had past parvovirus B19 infection, and 1 was negative for parvovirus B19). Analysis of the parvovirus B19 status of 40 adult IgG aPL-positive patients showed that 33 (83%) were anti-IgG VP1/VP2-positive, and viral DNA was detected in 11 patients (28%). Ten of these 11 viremic patients were in the subgroup of 28 IgG aPL-positive SLE patients. CONCLUSION: Antiphospholipid antibodies are preferentially found in serum of children with juvenile idiopathic arthritis who have been previously infected with parvovirus B19 and have established, persistent infection. Adult patients with IgG aPL positivity have a high incidence of persistent parvovirus B19 infection. We conclude that parvovirus B19 might be directly involved in the elicitation of autoimmune reactions partly mediated by aPL.     

Environmental influences on inflammatory bowel disease manifestations. Lessons from epidemiology

Environmental factors play an important role in the disease manifestation, course and prognosis of inflammatory bowel disease. Observations on temporal trends and geographical distribution point at risk factors associated with a Western lifestyle. A large number of studies have been performed on various factors such as diet, smoking, and several infectious agents. Childhood exposures modifying immune responses in later life form a particularly interesting field. However, so far, only smoking in Crohn's disease, and smoking cessation in ulcerative colitis can be considered established as risk factors for the manifestation of the disease. Smoking is also associated with a poor prognosis in Crohn's disease. A strong negative association of appendectomy with ulcerative colitis has been very consistent across many studies; however, the implications of this finding are still obscure.     

Adipocytokines: leptin--the classical, resistin--the controversical, adiponectin--the promising, and more to come

With the growing prevalence of obesity, scientific interest in the biology of adipose tissue has been extended to the secretory products of adipocytes, since they are increasingly shown to affect several aspects in the pathogenesis of obesity-related diseases. The cloning of the ob gene is consistent with this concept and suggests that body fat content in adult rodents is regulated by a negative feedback loop centred in the hypothalamus. In recent years, a number of additional signalling molecules secreted by adipose tissue have been discovered, commonly referred to as 'adipocytokines'. Among these, adiponectin is perhaps the most interesting and promising compound for the clinician since it has profound protective actions in the pathogenesis of diabetes and cardiovascular disease. Adiponectin is low in obese subjects and, in particular, insulin-resistant patients. In contrast, resistin seems to be of greater relevance in relation to the immune stress response than in the regulation of glucose homeostasis. However, inflammatory processes have recently been connected with the development of atherosclerosis. Finally, little is known regarding the clinical relevance of visfatin. Recent research has revealed many functions of adipocytokines extending far beyond metabolism, such as immunity, cancer and bone formation. This report aims to review some of the recent topics of adipocytokine research that may be of particular importance.