Age‐related motor dysfunction and neuropathology in a transgenic mouse model of multiple system atrophy

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a progressive degeneration of the striatonigral, olivo‐ponto‐cerebellar, and autonomic systems. Glial cytoplasmic inclusions (GCIs) containing alpha‐synuclein represent the hallmark of MSA and are recapitulated in mice expressing alpha‐synuclein in oligodendrocytes. To assess if oligodendroglial expression of human wild‐type alpha‐synuclein in mice (proteolipid promoter, PLP‐SYN) could be associated with age‐related deficits, PLP‐SYN and wild‐type mice were assessed for motor function, brain morphometry, striatal levels of dopamine and metabolites, dopaminergic loss, and distribution of GCIs. PLP‐SYN displayed age‐related impairments on a beam‐traversing task. MRI revealed a significantly smaller brain volume in PLP‐SYN mice at 12 months, which further decreased at 18 months together with increased volume of ventricles and cortical atrophy. The distribution of GCIs was reminiscent of MSA with a high burden in the basal ganglia. Mild dopaminergic cell loss was associated with decreased dopamine turnover at 18 months. These data indicate that PLP‐SYN mice may recapitulate some of the progressive features of MSA and deliver endpoints for the evaluation of therapeutic strategies. Synapse 68:98–106, 2014. © 2013 Wiley Periodicals, Inc.     

Nicht-invasive Beatmung

Zum Thema Die nicht-invasive Beatmung (NIV) über eine Maske erm?glicht bei vielen Patienten eine effiziente Beatmung unter Vermeidung der Risiken und Nebenwirkungen der endotrachealen Intubation. Für die chronisch-obstruktive Lungenerkrankung (COPD) sind die Vorteile der Maskenbeatmung im Hinblick auf Beatmungsdauer, Dauer der Intensivbehandlung, Prognose und Behandlungskosten inzwischen relativ gut durch Studien belegt. Bei anderen Indikationen –“Nicht-COPD-Patienten”– erlauben die verfügbaren Daten noch kein gesichertes Urteil, rechtfertigen aber einen Behandlungsversuch auch au?erhalb von Studien in klinischer Routine. Nachteilig sind der initial h?here personelle Betreuungsaufwand bei NIV sowie die stark von der Erfahrung abh?ngige Erfolgsrate. Die wichtigste Voraussetzung für eine erfolgreiche nicht-invasive Beatmung in der Intensivmedizin ist die Bereitschaft von ?rzten und Pflegepersonal, eine ungewohnte Beatmungsphilosophie zu akzeptieren und die relativ einfache Technik der Maskenbeatmung zu erlernen. Bei Beherrschung der Technik kann die NIV aber eine wertvolle Hilfe vom Notarztwagen bis zur Intensivstation sein.     

Venous thromboembolism in trauma: a local manifestation of systemic hypercoagulability?

BACKGROUND: The purpose of this study was to evaluate the relative importance of systemic hypercoagulability, preexisting and acquired risk factors, and specific injury patterns in the development of venous thromboembolism (VTE) after injury. METHODS: Injured patients with an Injury Severity Score > or = 15 were followed with lower extremity venous duplex ultrasonography, prothrombin fragment 1 + 2, and quantitative D-dimer levels at 1 and 3 days and then weekly until discharge. RESULTS: Among 101 patients with a mean Injury Severity Score of 27.3 +/- 10.5 followed for 12.4 +/- 8.7 days, 28 (27.7%) developed a lower extremity thrombosis, 2 (1.9%) sustained a pulmonary embolism, and 1 (0.9%) had a symptomatic upper extremity thrombosis. Although admission fragment 1 + 2 and D-dimer levels were elevated in 81.4% and 100% of patients, respectively, mean levels were not significantly different in those with or without VTE. VTE was more common (p < 0.05) among those with obesity, age > 40 years, immobilization for > 3 days, spine fractures, and lower extremity fractures. However, only obesity (p = 0.004) and immobilization > 3 days (p = 0.05) were independent predictors of VTE in a multivariate analysis. CONCLUSION: Although elevated in seriously injured patients, neither markers of activated coagulation nor specific injury patterns are predictive of VTE. Associations with immobilization and obesity suggest that VTE after injury is a systemic hypercoagulable disorder with local manifestations of thrombosis related to lower extremity stasis.     

Relation of coronary artery disease and cerebrovascular disease with atherosclerosis of the thoracic aorta in the general population.

The association between clinical coronary artery disease, cerebrovascular disease, and aortic atherosclerosis has not been examined in the general population. Transesophageal echocardiography was performed in 581 subjects, a random sample of the Olmsted County (Minnesota) population aged >/=45 years, participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. The frequency and severity of atherosclerosis of the thoracic aorta were determined in the population and the association between clinical coronary artery disease, cerebrovascular disease, and aortic atherosclerosis was examined. Previous myocardial infarction, angina pectoris, and coronary artery bypass surgery were significantly associated with aortic atherosclerosis, adjusting for age and gender (p 4-mm thick, ulcerated plaques, or mobile debris), adjusting for age and gender (p <0.05). Age, smoking, pulse pressure, previous myocardial infarction (odds ratio [OR] 4.67; 95% confidence interval [CI] 1.42 to 15.40), and coronary artery bypass surgery (OR 5.12; 95% CI 1.01 to 26.01) were independently associated with aortic atherosclerosis. Among subjects with atherosclerosis, age, smoking, pulse pressure, hypertension treatment, and coronary artery disease (OR 2.50; 95% CI 1.18 to 5.30) were independently associated with complex atherosclerosis. Weak associations were observed between previous ischemic stroke, transient ischemic attack, and aortic atherosclerosis, associations that were not significant after age- and gender-adjustment (p >0.2). Thus, coronary artery disease is strongly associated with aortic atherosclerosis and complex atherosclerosis in the general population. Cerebrovascular disease is weakly associated with aortic atherosclerosis, thereby questioning the overall importance of aortic atherosclerosis in the pathogenesis of cerebrovascular events in the general population.