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The cardiac troponin C mutation Leu29Gln found in a patient with hypertrophic cardiomyopathy does not alter contractile parameters in skinned murine myocardium
Full text linkThe present study investigates the effects of the first mutation of troponin C (hcTnC(L29Q)) found in a patient with hypertrophic cardiomyopathy (HCM) on force-pCa relations and the interplay with phosphorylation of sarcomeric PKA substrates. In triton-skinned murine cardiac fibers, the endogenous mcTnC was extracted and the fibers were subsequently reconstituted with recombinant wild-type and mutant hcTnC. Force-pCa relations of preparations containing hcTnC(L29Q) or hcTnC(WT) were similar. Incubation of fibers reconstituted with the recombinant proteins with phosphatase to dephosphorylate sarcomeric PKA substrates induced an increase in Ca(2+) sensitivity, slightly more pronounced (0.04 pCa units) in hcTnC(L29Q)-containing fibers. Incubation of the dephosphorylated fibers with PKA induced significant rightward shifts of force-pCa relations of similar magnitude with both, hcTnC(L29Q) and hcTnC(WT). No significant effects of hcTnC(L29Q) on the velocity of unloaded shortening were observed. In conclusion, no major differences in contractile parameters of preparations containing hcTnC(L29Q) compared to hcTnC(WT) were observed. Therefore, it appears unlikely that hcTnC(L29Q) induces the development of HCM by affecting the regulation of Ca(2+)-activated force and interference with PKA-mediated modulation of the Ca(2+) sensitivity of contraction
Image-guided Transcranial Doppler Sonography for Monitoring of Defined Segments of Intracranial Arteries
No full textImage guidance to improve reliability and data integrity of transcranial Doppler sonography
No full textBackground: Principles and accuracy of image-guided transcranial Doppler (IG TCD) sonography have been published recently. However, it remains open whether combination of image guidance and TCD offers an additional clinical advantage. This study scores the accuracy of conventional TCD examinations and investigates the potential improvement of TCD data integrity and reliability regarding the additional use of IG. Methods: Conventional TCD was performed by a group of experienced investigators, who were blinded to images of a navigation system tracking the Doppler probe, whereas an independent observer documented the TCD findings, acquired by the investigators, due to saving spatial data of the TCD sample volume using IG for subsequent analysis. In a second set of experiments, image guidance was available to investigators without any previous TCD experience. Results: The analysis of 3D data of vessels (n = 173) labeled by experienced investigators in conventional TCD, revealed a rate of 37% misinterpreted Doppler signals regarding the target vessel. Correctness of labeling was comparable between the different vascular segments. The rate of correct labeling was higher for right- (69%) than for left-sided vessels (57%). In comparison, by using IG, TCD investigators without any previous TCD experience achieved a significantly lower rate of 10% (n = 39) mislabeled vessels. Conclusions: Our data suggest, that misinterpretation of the vascular source of the Doppler signal is a common source of errors in conventional TCD. Visualization of the vascular anatomy by image guidance offers improved accuracy and reliability of TCD results and may positively influence the learning curve for inexperienced investigators. (C) 2013 Published by Elsevier B.V
Einfluss der neutrophilen Granulozyten auf die Blut- Hirn- Schranken- Störung in einem experimentellen Modell der Subarachnoidalblutung
No full textunclear. In the pathophysiology of other diseases, a neutrophil-induced disruption of the blood-brain barrier (BBB) was shown to play a major role. We therefore examined the effect of neutrophils on the BBB in the first 24 hours after SAH in a murine endovascular filament perforation model of SAH.
Methods
SAH was induced in C57BL/6N mice by endovascular filament perforation. Neutropenia was induced by anti-Ly6G antibody injection 12 h prior to surgery, successful induction of neutropenia was verified by differential leukocyte counts at the end of the experiment. Animals were sacrificed at 15 min, 3 h, and 24 h after SAH. The brains were dissected and frozen in powdered dry ice, cryosections were obtained, and IgG fluorescence staining was performed. Positive IgG fluorescence was taken as a surrogate parameter for BBB disruption. The area with BBB disruption was determined for the left hemisphere. Data are expressed in percent relative to the ipsilateral hemisphere. The Mann-Whitney U test was used for statistical analysis with p < 0.05 considered as statistically significant.
Results
51 animals were assigned to either sham surgery or SAH induction with or without prior induction of neutropenia. SAH induction without prior induction of neutropenia induced a sharp increase in the area with BBB disruption (SAH, 15 min: 6,27 ± 3,35%, 3 h: 16,02 ± 6,35%, 24 h: 21,71 ± 5,58%), which was not present after sham surgery (sham, 15 min: 5,16 ± 1,64%, 3 h: 5,93 ± 4,18%, 24 h: 6,65 ± 6,71%). After induction of neutropenia, SAH-induced disruption of the BBB was attenuated compared to SAH alone (SAH and neutropenia, 15 min: 2,36 ± 2%, 3 h: 8,66 ± 5,83%, 24 h: 5,42 ± 3,84%), which reached statistical significance at 24 h post-SAH.
Conclusion
Already in the first hours after SAH, neutrophils induce a disruption of the BBB. Targeting neutrophil function or neutrophil interaction with the neurovascular unit could therefore be a promising strategy to mitigate BBB disruption after SAH. More studies are needed to examine whether the early neutrophil-induced BBB disruption is the critical phenomenon that leads to activation of cerebral inflammation in the weeks after SAH.ca. 85 Seite
Image-guided Intracranial Endosonography
No full textBackground: Although the skull limits applicability of sonography, bedside intracranial endosonography might be an alternative to computed tomography scans to detect adverse events in sedated patients. However, the usefulness of intracranial endosonography for potential clinical application has not been evaluated. The present study was designed to investigate the suitability of an image-guided intracranial endosonography (IGIE) catheter for intracranial ultrasound imaging in an ex vivo phantom model and in a large animal model.Materials and Methods: IGIE was evaluated in a cranial phantom and a porcine intracranial hemorrhage (ICH) model. Two anesthetized animals underwent an initial magnetic resonance imaging (MRI) scan, followed by placement of an endosonography catheter in the frontal lobe. After anatomic imaging, an experimental ICH was placed in the contralateral hemisphere. B-scan imaging, duplex, Doppler sonography, and a second MRI were performed. A standard image-guiding device tracked the ultrasound catheter.Results: Endosonography provided high-definition imaging of intracranial structures. Image guidance allowed direction of the catheter to and intuitive identification of anatomic structures. Doppler imaging allowed analysis of blood flow in intracranial vessels. Ultrasound imaging was used to monitor evolution of ICH and the resulting brain edema in real time. Coregistration of ultrasound and MRI images acquired after ICH placement demonstrated the high accuracy of the spatial resolution of IGIE (largest mismatch <5 mm).Conclusions: IGIE provides high-definition images of intracranial structures, Doppler analysis of blood flow, and real-time monitoring of intracranial structural lesions. We suggest that IGIE might prove a valuable tool for intracranial monitoring of sedated patients over extended time periods
Microsurgical fenestration of perineural cysts to the thecal sac at the level of the distal dural sleeve
Full text linkBackground Surgery for symptomatic sacral perineural cysts remains an issue of discussion. Assuming micro-communications between the cyst and thecal sac resulting in a valve mechanism and trapping of CSF as a pathomechanism, microsurgical fenestration from the cyst to the thecal sac was performed to achieve free CSF communication. Methods In 13 consecutive patients (10 female, 3 male), MRI revealed sacral perineural cysts and excluded other pathologies. Micro-communication between the thecal sac and the cysts was shown by delayed contrast filling of the cysts on postmyelographic CT. Surgical fenestration achieved free CSF communication between the thecal sac and cysts in all patients. The patient histories, follow-up examinations and self-assessment scales were analyzed. Symptoms at initial presentation included lumbosacral pain, pseudoradicular symptoms, genital pain and urinary dysfunction. Mean follow-up was 10.7 +/- 6.6 months. Findings Besides one CSF fistula, no surgical complications were observed. Five patients did not improve after surgery\; in four of these cases multiple cysts were found, but small and promptly filling cysts remained untreated. Seven patients reported lasting benefit following surgery\; three of these had single cysts, and all had cysts >1 cm. One patient initially benefited from cyst fenestration but experienced recurrent pain within 2 months postoperatively. Re-myelography revealed delayed contrast filling of the recurrent cyst\; however, surgical revision did not lead to an improvement despite successful fenestration and collapse of the cyst revealed by postoperative imaging. Conclusions Microsurgical fenestration of sacral perineural cysts to the thecal sac is a surgical approach that has shown success in the treatment of lumbosacral pain, pseudoradicular symptoms, genital pain and urinary dysfunction associated with sacral perineural cysts. Our analysis, however, shows that mainly patients with singular large cysts benefit from this treatment
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Evaluation of efficacy and biocompatibility of a novel semisynthetic collagen matrix as a dural onlay graft in a large animal model
Full text linkSemisynthetic collagen matrices are promising duraplasty grafts with low risk of cerebrospinal fluid (CSF) fistulas, good tissue integration and minor foreign body reaction. The present study investigates the efficacy and biocompatibility of a novel semisynthetic bilayered collagen matrix (BCM, B. Braun Aesculap) as dural onlay graft for duraplasty. Thirty-four pigs underwent osteoclastic trepanation, excision of the dura, and placement of a cortical defect, followed by duraplasty using BCM, Suturable DuraGen (TM) (Integra Neuroscience), or periosteum. CSF tightness and intraoperative handling of the grafts were evaluated. Pigs were sacrificed after 1 and 6 months for histological analysis. BCM and DuraGen (TM) showed superior handling than periosteum with a trend for better adhesion to dura and CSF tightness for BCM. Periosteum, which was sutured unlike the synthetic grafts, had the highest intraoperative CSF tightness. Duraplasty time with periosteum was significantly higher (14.4 +/- 2.7 min) compared with BCM (2.8 +/- 0.8 min) or DuraGen (TM) (3.0 +/- 0.5 min). Tissue integration by fibroblast infiltration was observed after 1 month for all devices. More adhesions between graft and cortex were observed with DuraGen (TM) compared with BCM and periosteum. No relevant adhesions between leptomeninges and BCM were observed and all devices showed comparable lymphocytic reaction of the brain. All devices were completely integrated after 6 months. BCM and DuraGen (TM) showed a trend for an enhanced lymphocytic reaction of the brain parenchyma compared with periosteum. Implant rejection was not observed. Semisythetic collagen matrices are an attractive alternative in duraplasty due to their easy handling, lower surgical time, and high biocompatibility.B. Braun Aesculap AG, Tuttlingen, German
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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