Standardisierte Kontrastmittelsonographie (CEUS) in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin (CEUS-Akut)

Die Anaesthesiologie -     

Is Involvement a Good Thing? The Undesirable Consequences of Topical and Conversational Involvement in the Context of Alcohol Consumption

Whereas there is evidence that interpersonal communication, or conversation, influences predictors of alcohol consumption, the role of involvement in conversation effects remains unclear. This study explored how three aspects of involvement (topical relevance, or how relevant the topic of alcohol is; conversational relevance, or how relevant a conversation about alcohol is; and conversational effort, or how much effort people put into such a conversation), influence conversation effects. After assessing topical relevance, 46 same-sex dyads were requested to talk about the negative consequences of heavy drinking. Within each dyad, one participant was asked to take on an active talking role and the other participant a passive listening role. Next, conversational relevance, effort, and predictors of heavy drinking were measured. Results showed that participants who drank more alcohol found the topic of heavy drinking more relevant. This topical relevance increased conversational relevance and conversational effort. Conversational effort further increased when a talking role was assigned. Furthermore, participants who put more effort in the conversation and found it more relevant had more positive norms, identified more strongly with alcohol, and had higher intentions to drink. These findings suggest that more involvement in an alcohol-related conversation does not always lead to desirable outcomes.     

Application of the adverse outcome pathway framework to genotoxic modes of action

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.     

Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

Ischemia independent lesion evolution during focal stroke in rats

Lesion evolution during focal cerebral ischemia may depend on flow restrictions or on accumulation of toxic mediators within the infarct and expansion of these factors to the periinfarct region. So far, the precise contribution of flow dependent versus spreading-mediated impairment of viable periinfarct tissue has not been determined. Therefore, we measured lesion expansion, flow restrictions and glutamate distribution on serial brain sections at different time points after experimental focal ischemia.Permanent focal ischemia was induced by occlusion of the right middle cerebral artery in male rats and the flow reduction was subsequently measured at 1, 12 and 24 h using iodo[¹⁴C]antipyrine autoradiography. Additionally, the necrotic volume was determined on serial brain sections and the glutamate content was measured in tissue samples from adjacent microdissections.Twelve hours after focal ischemia no noteworthy viable areas with blood flow restrictions of 20-40 ml 100 g^− 1 min^− 1 existed but at 24 h the necrotic tissue exceeded the hemodynamically compromised region by 40 ± 21 mm³ (24%). Furthermore, at 12 and 24 h the glutamate content was elevated in areas surrounding the infarct.Relevant flow restrictions are detectable only during early stages of infarct maturation, whereas the propagation of secondary factors may be the predominant mechanism for delayed infarct evolution.     

Multidisciplinary evaluation of rat renal cell carcinoma

The rat renal cell carcinoma system as described by deVere White and Olsson in 1980 is used widely as a model for its human counterpart. The tumor arose spontaneously in a male Wistar Lewis rat and its behaviour has been shown to be stable during multiple passages. We have compared this tumor with the human renal cell carcinoma using a multidisciplinary approach. Light microscopy and electron microscopy showed a great resemblance of this rat tumor to a human renal cell carcinoma of the clear cell type with the ultrastructural presence of desmosomes. With the use of tissue specific antibodies against intermediate filament proteins, it could be shown that their expression is comparable to human renal cell carcinoma, i.e. coexpression of vimentin and different cytokeratins in the tumor cells. The cells could also be shown to contain cytokeratin 18. An aneuploid cell population in the tumor, expressing both vimentin and keratin, could be characterized by DNA flow cytometry in double labeling experiments. Comparison of normal and malignant rat kidney tissue by Northern blot analysis revealed increased levels of vimentin mRNA. In conclusion, this tumor model seems to have several histological and biological properties in common with the human renal tumor.     

Das Krankheitsbild der unspezifischen Epididymitis und seine Differentialdiagnose

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