Lack of association between polymorphisms of the toll-like receptor 4 gene and cerebral ischemia

Abstract. Toll-like receptor-4 (TLR4), an important mediator of the innate immune response, is expressed in atherosclerotic lesions. The common single nucleotide exchange (Asp299Gly) of the TLR4 gene has been previously reported to impair TLR4 function and to be associated with a decreased risk of carotid atherosclerosis. Therefore, we aimed to detect the potential impact of TLR4 genotypes on the risk of cerebral ischemia.We studied the prevalence of two common polymorphisms of the TLR4 gene (Asp299Gly and Thr399Ile) in 3 independent study populations: (1.) in a cross-sectional study including 769 patients either with type 1 or type 2 diabetes mellitus, of whom 56 (7.2%) had a history of cerebral ischemia (study 1), (2.) a case-control study (study 2) including 128 consecutive patients with cerebral ischemia, mean age 60 ± 10.9 years and 139 control subjects, and (3.) a case-control study (study 3) including 171 young adults aged < 50 years with cerebral ischemia and 204 control individuals. In all subjects, Asp299Gly and Thr399Ile were detected by restriction length analysis.The prevalence of the TLR4 genotypes was essentially the same between patients with cerebral ischemia and control subjects in all 3 study populations. Furthermore, there was also no association with the subgroup of atherosclerotic stroke in both case-control studies populations.Although TLR4 polymorphisms are associated with a decreased risk of carotid atherosclerotic lesions, our findings indicate that they do not influence the prevalence of cerebral ischemia. This implies that the Asp299Gly TLR4-allele might have a protective role in carotid atherosclerosis, but not in cerebral ischemia.* both authors contributed equally to this work     

High-frequency stimulation of the entopeduncular nucleus improves dystonia in dtsz hamsters

High-frequency stimulation (HFS) of the internal pallidum (GPi) has been reported to improve generalized dystonia in patients. Currently, dystonia is thought to be associated with disturbed neuronal activity of GPi neurons. Similar findings have been observed in the dtsz hamster, a model of idiopathic paroxysmal non-kinesiogenic dystonia. For this reason, we investigated the effect of bilateral HFS of the entopeduncular nucleus (EPN, rodent homologue of GPi) on the severity of dystonia. Bilateral EPN-HFS resulted in a reversible decrease of dystonia severity up to 50% when compared to both pre- and post-HFS scores, and controls. Our results underline the pathophysiological role of the EPN in the dtsz hamster and suggest the suitability of this model to further investigate mechanisms of HFS in dystonia.     

Bone marrow microenvironment facilitating dendritic cell: CD4 T cell interactions and maintenance of CD4 memory

This study shows that bone marrow (BM) stroma expresses constitutively multiple adhesion molecules (ICAM-1, VCAM-1, MadCAM-1, P-selectin) relevant for the homing and infiltration of BM by blood derived T lymphocytes, and also the co-stimulatory molecule CD80, relevant for T cell activation. T cells were capable of homing to BM but not to thymus. Homing to BM involved the integrins LFA-1alpha and alpha4 which interact with the above constitutively expressed cell adhesion molecules (CAMs). CD3 T cells were detected together with BM resident CD11c dendritic cells (DCs), often enriched in follicle-like structures in BM parenchyma. Cognate interactions between transferred antigen specific transgenic CD4 T cells and antigen laden BM-DCs led to formation of multicellular clusters in situ in BM, to generation of lymphoblasts and to clonal T cell expansion within such clusters. The great majority of BM-CD4 T cells had a memory phenotype suggesting that the BM microenvironment facilitates maintenance of CD4 memory. These results extend and corroborate our previous findings on BM-CD8 T cell mediated immune responses. Together these findings suggest that DC-T cell interactions in BM play an important role in immune responses to blood-borne antigen and in the establishment of systemic immunity and long-term memory.     

Detection of alternatively spliced EMR2 mRNAs in colorectal tumor cell lines but rare expression of the molecule in colorectal adenocarcinomas

EMR2 and CD97, members of the epidermal growth factor (EGF)-TM7 family, show a very high homology. CD97, whose expression is closely related to clinical tumor stage in colorectal carcinomas, potentially functions as an adhesion molecule. Nothing is known about the presence of EMR2 in these tumors. We systematically examined the expression of EMR2 in colorectal carcinoma cell lines and adenocarcinomas. Of 18 cell lines, 10 were only slightly positive for EMR2 according to flow cytometry. Various EMR2 splice variants, including a new isoform, have been detected at the mRNA level. EMR2 expression did not correlate with in vitro migration or invasion capacity of the cell lines. Normal colorectal epithelial cells were EMR2 negative. In contrast to CD97, which is found in most colorectal adenocarcinomas, only 8 of 81 of these tumors expressed EMR2. No correlation was found between EMR2 expression and clinicopathological parameters of the tumors. In summary, a significant but low number of colorectal carcinomas are positive for EMR2, indicating different roles for this molecule and CD97 in these tumors.     

Modernes Wundmanagement mit ultraschallassistierter Wundreinigung

Zusammenfassung Zunehmende ökonomische Zwänge und deren Lösungsversuche zeigen ihre Auswirkungen. Selbst im klinischen Sprachgebrauch hat eine Dynamisierung stattgefunden, die den Bemühungen Rechnung trägt. So hat sich die Wundpflege über das Verbandsregime zum Wundmanagement gewandelt. Dieser Begriff impliziert aktive Maßnahmen und stellt das passive Zuwarten hintan.Seit einiger Zeit setzen wir ein Gerät zur Applikation von Leistungsultraschall bei der Behandlung vorwiegend chronischer Wunden unterschiedlicher Genese ein. Ziel ist—in Ergänzung etablierter Verbandsschemata—die schnellere Konditionierung der Wunden durch Reinigung und Granulationsförderung zur Verkürzung der Heilungsphase. Aufgrund der bisher gemachten Erfahrungen überzeugt die ultraschallassistierte Wundreinigung durch eine einfache und schmerzarme Anwendung, sichtbare Erfolge, gute Compliance der Patienten sowie Schonung der operativen Ressourcen.     

Modernes Wundmanagement mit ultraschallassistierter Wundreinigung

Zunehmende ökonomische Zwänge und deren Lösungsversuche zeigen ihre Auswirkungen. Selbst im klinischen Sprachgebrauch hat eine Dynamisierung stattgefunden, die den Bemühungen Rechnung trägt. So hat sich die Wundpflege über das Verbandsregime zum Wundmanagement gewandelt. Dieser Begriff impliziert aktive Maßnahmen und stellt das passive Zuwarten hintan.Seit einiger Zeit setzen wir ein Gerät zur Applikation von Leistungsultraschall bei der Behandlung vorwiegend chronischer Wunden unterschiedlicher Genese ein. Ziel ist—in Ergänzung etablierter Verbandsschemata—die schnellere Konditionierung der Wunden durch Reinigung und Granulationsförderung zur Verkürzung der Heilungsphase. Aufgrund der bisher gemachten Erfahrungen überzeugt die ultraschallassistierte Wundreinigung durch eine einfache und schmerzarme Anwendung, sichtbare Erfolge, gute Compliance der Patienten sowie Schonung der operativen Ressourcen.     

R1 – Systemic thrombolysis in German stroke units

BACKGROUND: Systemic thrombolysis with tissue plasminogen activator (t-PA) for treatment of acute ischemic stroke was approved in Germany in 2000. Up to now, only data from single centers have been available for the study of the use of thrombolysis in a hospital-based approach outside controlled trials. We therefore sought to determine the frequency of application and complications as well as the patient outcome after t-PA treatment in clinical routine of specialized stroke centers in Germany. METHODS: Within the German Stroke Data Bank Collaboration, 6234 consecutive patients with ischemic stroke were prospectively documented in 20 stroke centers between 1998 and 1999. The patients were centrally followed via telephone interview after 3 months and 1 year to assess global functional outcome using the Modified Rankin Scale. RESULTS: 250 patients (4 %) received systemic t-PA treatment during the study period. The baseline characteristics of these patients were comparable to large clinical trials and phase IV studies. Symptomatic and asymptomatic parenchymal hemorrhage occurred in 22 patients (8.8 %) and was fatal in 3 patients. Follow-up data after 3 months were obtained in 82.4 % of all patients, of which 35 % had a favorable functional outcome (mRS /= 4) and 17 % had died. CONCLUSION: The results of our study agree with the assumption that thrombolytic therapy can be performed safely and effectively in daily clinical practice. Nevertheless, the small proportion of patients receiving thrombolysis even in specialized stroke centers calls for further improvement of acute stroke management in Germany.