Amyloidosis is associated with thicker myelin and increased oligodendrogenesis in the adult mouse brain

In Alzheimer's disease, amyloid plaque formation is associated with the focal death of oligodendrocytes and soluble amyloid β impairs the survival of oligodendrocytes in vitro. However, the response of oligodendrocyte progenitor cells (OPCs) to early amyloid pathology remains unclear. To explore this, we performed a histological, electrophysiological, and behavioral characterization of transgenic mice expressing a pathological form of human amyloid precursor protein (APP), containing three single point mutations associated with the development of familial Alzheimer's disease (PDGFB-APP^Sw.Ind, also known as J20 mice). PDGFB-APP^Sw.Ind transgenic mice had impaired survival from weaning, were hyperactive by 2 months of age, and developed amyloid plaques by 6 months of age, however, their spatial memory remained intact over this time course. Hippocampal OPC density was normal in P60-P180 PDGFB-APP^Sw.Ind transgenic mice and, by performing whole-cell patch-clamp electrophysiology, we found that their membrane properties, including their response to kainate (100 µM), were largely normal. However, by P100, the response of hippocampal OPCs to GABA was elevated in PDGFB-APP^Sw.Ind transgenic mice. We also found that the nodes of Ranvier were shorter, the paranodes longer, and the myelin thicker for hippocampal axons in young adult PDGFB-APP^Sw.Ind transgenic mice compared with wildtype littermates. Additionally, oligodendrogenesis was normal in young adulthood, but increased in the hippocampus, entorhinal cortex, and fimbria of PDGFB-APP^Sw.Ind transgenic mice as pathology developed. As the new oligodendrocytes were not associated with a change in total oligodendrocyte number, these cells are likely required for cell replacement.     

肝癌门静脉癌栓的介入治疗

肝癌合并门静脉癌栓(PVTT)的治疗仍是医学难题,既往一直被视为手术禁忌,近年随着介入医学的进步,发展了多种微创治疗方法,取得了可喜的疗效,使肝癌并PVTT由不可治变为部分可治,展现了介入方法治疗肝癌并PVTT的乐观前景.本文就当前针对门静脉癌栓的介入治疗方法,技术要点及各种介入治疗方法的初步疗效进行了综述.为进一步的临床规范化综合治疗肝癌并门静脉癌栓提供参考.     

Epidemiologie des Schwerverletzten Eine prospektive Erfassung der pr?klinischen und klinischen Versorgung Eine prospektive Erfassung der pr?klinischen und klinischen Versorgung

Trotz der gro?en medizinischen und sozio?konomischer Bedeutung der schweren Mehrfachverletzung existieren nur wenige aktuelle Daten zur Beschreibung dieses Kollektivs. Ziel der Untersuchung war es, die von 1993 – 1997 prospektiv und multizentrisch erfa?ten 2069 Patienten des DGU-Traumaregisters epidemiologisch zu untersuchen. Es erfolgte eine deskriptive Analyse der Inzidenz der Verletzungen und Komplikationen im Patientenkollektiv und des Umfanges therapeutischer Ma?nahmen. Der Verkehrsunfall war mit 56,7% die h?ufigste Unfallursache, das Durchschnittsalter betrug 38,5 ± 18,7 Jahre, das Verh?ltnis m?nnlich zu weiblich 2,6:1. Bei einem “Injury Severity Score” (ISS) von durchschnittlich 22,2 ± 13,1 Punkten war bei fast ausschlie?lich stumpfen Verletzungen das Thoraxtrauma die h?ufigste relevante Verletzung (AIS der Region Thorax ≥ 3 Punkte, 44,5%). Das Sch?del-Hirn-Trauma (SHT) mit einem AIS ≥ 3 (39,2%) beeinflu?te die Frühletalit?t (Tod ≤ 24 h nach Trauma, 51,7% der Verstorbenen) und die Gesamtklinikletalit?t (18,6%); 68,9% der Patienten zeigten Extremit?tenverletzungen; 71,7% der Patienten wurden im Bereitschaftsdienst aufgenommen (16–8 Uhr werktags, Wochenenden und Feiertage). Die Verletzten wurden Median 4 Tage beatmet, 6 Tage intensivstation?r behandelt und verweilten 19 Tage im Krankenhaus. An Komplikationen wurden Organversagen (Lunge 22%, Kreislauf 18,7%, Leber 9,6%, Niere 3,1%) und Sepsis (11,6%) erfa?t. Die durchgeführte epidemiologische Analyse stellt eine umfassende Beschreibung eines gro?en Kollektivs schwer Mehrfachverletzter dar. Die aktuellen Daten des DGU-Traumaregisters sind nutzbar zur Beantwortung wissenschaftlicher, klinischer und ?konomischer Fragen zum Qualit?tsmanagement.     

The role of skull base surgery for the treatment of adenoid cystic carcinoma of the sinonasal tract.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the sinonasal tract is an aggressive malignancy associated with a poor 5-year survival rate. The role of skull base surgery for the treatment of patients presenting with sinonasal ACC and its impact upon their survival has not previously been evaluated. METHODS: A retrospective review of 35 patients with ACC of the sinonasal tract who were treated with surgery and radiation therapy at the University of Pittsburgh Medical Center was performed to evaluate patient outcome. RESULTS: Local recurrence of tumor following surgery and radiation therapy was observed in 36% of the patients originally treated at the University of Pittsburgh Medical Center. Fourteen percent of these patients developed a regional tumor recurrence, and 21% developed distant metastases. We did not identify any tumor-related factors that predicted patient outcome. Local recurrences were treated with salvage surgical excision, and, despite aggressive management, only 1 of 17 patients with local recurrence was considered cured (NED) at 24 months (follow-up after salvage surgery). Overall, disease-free survival was 46.4%, at a median follow-up of 40 months. CONCLUSIONS: ACC of the sinonasal tract is an aggressive malignancy. Skull base surgery has facilitated the gross total excision of advanced lesions that were deemed inoperable in the past, but has not resulted in an overall improvement in disease-free survival. Local recurrence portends a very poor prognosis, despite aggressive salvage regimens. Alternative therapies for local recurrences warrant further investigation. Prospective, randomized studies are necessary to evaluate the outcome of patients treated with aggressive multimodal treatment regimens, including chemotherapeutic regimens.