Der Einfluss von Dexmedetomidin auf myokardiales Stunning und die transmyokardiale Perfusionsverteilung im chronisch instrumentierten wachen Hund

Beim myokardialen Stunning handelt es sich um eine postischämische kontraktile Dysfunktion, die nach Wiederherstellung der Perfusion trotz fehlender irreversibler Zellschädigung und trotz eines normalen koronaren Blutflusses persistiert. In der vorliegenden Arbeit wurden die Effekte einer präischämischen Gabe des hochselektiven alpha2-Agonisten Dexmedetomidin auf den Schweregrad und die Erholung von myokardialem Stunning sowie auf die transmyokardiale Perfusionsverteilung untersucht. Durch die Untersuchungen am Modell des chronisch instrumentierten Hundes konnte gezeigt werden, dass die intravenöse Gabe von Dexmedetomidin vor Induktion einer reversiblen Ischämie unter Antagonisierung des günstigen Bradykardieeffektes zu keiner Verbesserung der Erholung vom myokardialen Stunning sowie der ischämischen und postischämischen linksventrikulären systolischen Funktion führt

Prospective cohort study of radiotherapy with concomitant and adjuvant temozolomide chemotherapy for glioblastoma patients with no or minimal residual enhancing tumor load after surgery

Survival of glioblastoma patients has been linked to the completeness of surgical resection. Available data, however, were generated with adjuvant radiotherapy. Data confirming that extensive cytoreduction remains beneficial to patients treated with the current standard, concomitant temozolomide radiochemotherapy, are limited. We therefore analyzed the efficacy of radiochemotherapy for patients with little or no residual tumor after surgery. In this prospective, non-interventional multicenter cohort study, entry criteria were histological diagnosis of glioblastoma, small enhancing or no residual tumor on post-operative MRI, and intended temozolomide radiochemotherapy. The primary study objective was progression-free survival; secondary study objectives were survival and toxicity. Furthermore, the prognostic value of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation was investigated in a subgroup of patients. One-hundred and eighty patients were enrolled. Fourteen were excluded by patient request or failure to initiate radiochemotherapy. Twenty-three patients had non-evaluable post-operative imaging. Thus, 143 patients qualified for analysis, with 107 patients having residual tumor diameters ≤1.5 cm. Median follow-up was 24.0 months. Median survival or patients without residual enhancing tumor exceeded the follow-up period. Median survival was 16.9 months for 32 patients with residual tumor diameters >0 to ≤1.5 cm (95% CI: 13.3–20.5, p = 0.039), and 13.9 months (10.3–17.5, overall p < 0.001) for 36 patients with residual tumor diameters >1.5 cm. Patient age at diagnosis and extent of resection were independently associated with survival. Patients with MGMT promoter methylated tumors and complete resection made the best prognosis. Completeness of resection acts synergistically with concomitant and adjuvant radiochemotherapy, especially in patients with MGMT promoter methylation

Impact of Virtual Reality in Arterial Anatomy Detection and Surgical Planning in Patients with Unruptured Anterior Communicating Artery Aneurysms

Anterior-communicating artery (ACoA) aneurysms have diverse configurations and anatomical variations. The evaluation and operative treatment of these aneurysms necessitates a perfect surgical strategy based on review of three-dimensional (3D) angioarchitecture using several radiologic imaging methods. We analyzed the influence of 3D virtual reality (VR) reconstructions versus conventional computed tomography angiography (CTA) scans on the identification of vascular anatomy and on surgical planning in patients with unruptured ACoA aneurysms. Medical files were retrospectively analyzed regarding patient- and disease-related data. Preoperative CTA scans were retrospectively reconstructed to 3D-VR images and visualized via VR software to detect the characteristics of unruptured ACoA aneurysms. A questionnaire was used to evaluate the influence of VR on the identification of aneurysm morphology and relevant arterial anatomy and on surgical strategy. Twenty-six patients were included and 520 answer sheets were evaluated. The 3D-VR modality significantly influenced detection of the aneurysm-related vascular structure (p = 0.0001), the recommended head positioning (p = 0.005), and the surgical approach (p = 0.001) in the planning of microsurgical clipping. Thus, reconstruction of conventional preoperative CTA scans into 3D images and the spatial presentation in VR models enabled greater understanding of the anatomy and pathology, provided realistic haptic feedback for aneurysm surgery, and influenced operation planning and strategy

ADAMTS genes and the risk of cerebral aneurysm

OBJECTIVE Cerebral aneurysms (CAs) affect 2%-5% of the population, and familial predisposition plays a significant role in CA pathogenesis. Several lines of evidence suggest that genetic variations in matrix metalloproteinase genes (MMP) are involved in the etiopathology of CAs. The authors performed a case-control study to investigate the effect of 4 MMP variants from the ADAMTS family on the pathogenesis of CAs. METHODS To identify susceptible genetic variants, the authors investigated 8 single nucleotide polymorphisms (SNPs) in 4 genes from the ADAMTS family (ADAMTS2, -7, -12, and -13) known to be associated with vascular diseases. The study included 353 patients with CAs and 1055 healthy adults. RESULTS The authors found significant associations between CA susceptibility and genetic variations in 3 members of the ADAMTS family. The largest risk for CA (OR 1.32, p = 0.006) was observed in carriers of the ADAMTS2 variant rs11750568, which has been previously associated with pediatric stroke. Three SNPs under investigation are associated with a protective effect in CA pathogenesis (ADAMTS12 variant rs1364044: OR 0.65, p = 0.0001; and ADAMTS13 variants rs739469 and rs4962153: OR 0.77 and 0.63, p = 0.02 and 0.0006, respectively), while 2 other ADAMTS13 variants may confer a significant risk (rs2301612: OR 1.26, p = 0.011; rs2285489: OR 1.24, p = 0.02). CONCLUSIONS These results suggest that reduced integrity of the endothelial wall, as conferred by ADAMTS variants, together with inflammatory processes and defective vascular remodeling plays an important role in CA pathogenesis, although the mechanism of action remains unknown. The authors' findings may lead to specific screening of at-risk populations in the future

5-ALA Fluorescence in Native Pituitary Adenoma Cell Lines: Resection Control and Basis for Photodynamic Therapy (PDT)?

<div><p>Objective: Pituitary adenomas (PA), especially invasive ones, are often not completely resectable. Usage of 5-aminolevulinic acid (5-ALA) for fluorescence guided surgery could improve the rate of total resection and, additionally, open the doors for photodynamic therapy (PDT) in case of unresectable or partially resected PAs. The aim of this study was to investigate the uptake of 5-ALA and the effect of 5-ALA based PDT in cell lines. Methods: GH3 and AtT-20 cell lines were incubated with different concentrations of 5-ALA, protoporphyrin IX (PPIX) fluorescence was measured by flow cytometry and fluorescencespectrometry. WST-1 assays were performed to determine the surviving fraction of cells after PDT. PPIX fluorescence intensities and PDT effect of the pituitary adenoma cells were compared to U373MG, a well-known glioblastoma cell line. Results: Both cell lines showed a 5-ALA dependent intracellular PPIX fluorescence. Significant differences after 24hrs of incubation were observed in AtT-20 cells in comparison to GH3. Regardless of the incubation or metabolism time, there was a proliferation inhibiting effect after PDT, with no statistical significance. Conclusion: Since GH3 cells showed a heterogenous uptake of 5-ALA in the flow cytometry profile, but not constantly high concentrations they might have a 5-ALA efflux mechanism, which still needs to be determined. In the case of AtT-20, the cells might need a longer time for the uptake due to their size or slow metabolism. We showed that the different cell lines have different uptake and metabolism mechanisms, which needs to be further investigated. The general uptake of 5-ALA allows the possibility of resection control and PDT for pituitary adenomas. But, the role of PDT for unresectable pituitary adenomas deserves further investigations.</p></div

Spectrofluorometric measurment of GH3, AtT-20 and U373 MG cell lysates after excitation at 405nm.

<p>1x10⁶ cells were seeded and incubated with or without 5-ALA for 6 and 24hrs. The spectra from 450nm to 750nm was analyzed. For each experiment the untreated condition was subtracted from the 5-ALA treated measurement. Peak values at 631nm are compared after 6 and 24hrs of incubation in all three cell lines as arbitrary units (a.u.). Three to four independent experiments were performed and presented as box plot with min.-max. whiskers, one way ANOVA followed by Bonferroni’s post-hoc analysis was used for evaluating the statistical significance, * indicates p ≤ 0.05.</p