109 results on '"Friedl, Susanne'
Search Results
2. Low frequency oscillations reflect neurovascular coupling and disappear after cerebral death
- Author
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Sven Schulthess, Susanne Friedl, Gagan Narula, Giovanna Brandi, Jan Folkard Willms, Emanuela Keller, and Giulio Bicciato
- Subjects
Medicine ,Science - Abstract
Abstract Spectrum power analysis in the low frequency oscillations (LFO) region of functional near infrared spectroscopy (fNIRS) is a promising method to deliver information about brain activation and therefore might be used for prognostication in patients with disorders of consciousness in the neurocritical care unit alongside with established methods. In this study, we measure the cortical hemodynamic response measured by fNIRS in the LFO region following auditory and somatosensory stimulation in healthy subjects. The significant hemodynamic reaction in the contralateral hemisphere correlation with the physiologic electric response suggests neurovascular coupling. In addition, we investigate power spectrum changes in steady state measurements of cerebral death patients and healthy subjects in the LFO region, the frequency of the heartbeat and respiration. The spectral power within the LFO region was lower in the patients with cerebral death compared to the healthy subjects, whereas there were no differences in spectral power for physiological activities such as heartbeat and respiration rate. This finding indicates the cerebral origin of our low frequency measurements. Therefore, LFO measurements are a potential method to detect brain activation in patients with disorders of consciousness and cerebral death. However, further studies in patients are needed to investigate its potential clinical use.
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- 2024
- Full Text
- View/download PDF
3. Potential thresholds of critically increased cardiac-related spinal cord motion in degenerative cervical myelopathy
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Nikolai Pfender, Catherine R. Jutzeler, Michèle Hubli, Paulina S. Scheuren, Dario Pfyffer, Carl M. Zipser, Jan Rosner, Susanne Friedl, Reto Sutter, José M. Spirig, Michael Betz, Martin Schubert, Maryam Seif, Patrick Freund, Mazda Farshad, Armin Curt, and Markus Hupp
- Subjects
cervical cord ,spinal cord motion ,degenerative cervical myelopathy (DCM) ,cervical spondylotic myelopathy (CSM) ,phase contrast MRI (PC-MRI) ,spinal stenosis ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
IntroductionNew diagnostic techniques are a substantial research focus in degenerative cervical myelopathy (DCM). This cross-sectional study determined the significance of cardiac-related spinal cord motion and the extent of spinal stenosis as indicators of mechanical strain on the cord.MethodsEighty-four DCM patients underwent MRI/clinical assessments and were classified as MRI+ [T2-weighted (T2w) hyperintense lesion in MRI] or MRI− (no T2w-hyperintense lesion). Cord motion (displacement assessed by phase-contrast MRI) and spinal stenosis [adapted spinal canal occupation ratio (aSCOR)] were related to neurological (sensory/motor) and neurophysiological readouts [contact heat evoked potentials (CHEPs)] by receiver operating characteristic (ROC) analysis.ResultsMRI+ patients (N = 31; 36.9%) were more impaired compared to MRI− patients (N = 53; 63.1%) based on the modified Japanese Orthopedic Association (mJOA) subscores for upper {MRI+ [median (Interquartile range)]: 4 (4–5); MRI−: 5 (5–5); p
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- 2024
- Full Text
- View/download PDF
4. Increased cranio-caudal spinal cord oscillations are the cardinal pathophysiological change in degenerative cervical myelopathy
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Nikolai Pfender, Jan Rosner, Carl M. Zipser, Susanne Friedl, Martin Schubert, Reto Sutter, Markus Klarhoefer, José M. Spirig, Michael Betz, Patrick Freund, Mazda Farshad, Armin Curt, and Markus Hupp
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spinal cord motion ,spinal cord oscillations ,spinal stenosis ,degenerative cervical myelopathy ,phase contrast MRI ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
IntroductionDegenerative cervical myelopathy (DCM) is the most common cause of non-traumatic incomplete spinal cord injury, but its pathophysiology is poorly understood. As spinal cord compression observed in standard MRI often fails to explain a patient's status, new diagnostic techniques to assess DCM are one of the research priorities. Minor cardiac-related cranio-caudal oscillations of the cervical spinal cord are observed by phase-contrast MRI (PC-MRI) in healthy controls (HCs), while they become pathologically increased in patients suffering from degenerative cervical myelopathy. Whether transversal oscillations (i.e., anterior–posterior and right–left) also change in DCM patients is not known.MethodsWe assessed spinal cord motion simultaneously in all three spatial directions (i.e., cranio-caudal, anterior–posterior, and right–left) using sagittal PC-MRI and compared physiological oscillations in 18 HCs to pathological changes in 72 DCM patients with spinal canal stenosis. The parameter of interest was the amplitude of the velocity signal (i.e., maximum positive to maximum negative peak) during the cardiac cycle.ResultsMost patients suffered from mild DCM (mJOA score 16 (14–18) points), and the majority (68.1%) presented with multisegmental stenosis. The spinal canal was considerably constricted in DCM patients in all segments compared to HCs. Under physiological conditions in HCs, the cervical spinal cord oscillates in the cranio-caudal and anterior–posterior directions, while right–left motion was marginal [e.g., segment C5 amplitudes: cranio-caudal: 0.40 (0.27–0.48) cm/s; anterior–posterior: 0.18 (0.16–0.29) cm/s; right–left: 0.10 (0.08–0.13) cm/s]. Compared to HCs, DCM patients presented with considerably increased cranio-caudal oscillations due to the cardinal pathophysiologic change in non-stenotic [e.g., segment C5 amplitudes: 0.79 (0.49–1.32) cm/s] and stenotic segments [.g., segment C5 amplitudes: 0.99 (0.69–1.42) cm/s]). In contrast, right–left [e.g., segment C5 amplitudes: non-stenotic segment: 0.20 (0.13–0.32) cm/s; stenotic segment: 0.11 (0.09–0.18) cm/s] and anterior–posterior oscillations [e.g., segment C5 amplitudes: non-stenotic segment: 0.26 (0.15–0.45) cm/s; stenotic segment: 0.11 (0.09–0.18) cm/s] remained on low magnitudes comparable to HCs.ConclusionIncreased cranio-caudal oscillations of the cervical cord are the cardinal pathophysiologic change and can be quantified using PC-MRI in DCM patients. This study addresses spinal cord oscillations as a relevant biomarker reflecting dynamic mechanical cord stress in DCM patients, potentially contributing to a loss of function.
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- 2023
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5. Functional NIRS to detect covert consciousness in neurocritical patients
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Bicciato, Giulio, Narula, Gagan, Brandi, Giovanna, Eisele, Amanda, Schulthess, Sven, Friedl, Susanne, Willms, Jan Folkard, Westphal, Laura, and Keller, Emanuela
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- 2022
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6. Low frequency oscillations reflect neurovascular coupling and disappear after cerebral death
- Author
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Schulthess, Sven; https://orcid.org/0000-0002-1786-1670, Friedl, Susanne, Narula, Gagan; https://orcid.org/0000-0002-7445-3710, Brandi, Giovanna, Willms, Jan Folkard, Keller, Emanuela; https://orcid.org/0000-0002-7560-7574, Bicciato, Giulio, Schulthess, Sven; https://orcid.org/0000-0002-1786-1670, Friedl, Susanne, Narula, Gagan; https://orcid.org/0000-0002-7445-3710, Brandi, Giovanna, Willms, Jan Folkard, Keller, Emanuela; https://orcid.org/0000-0002-7560-7574, and Bicciato, Giulio
- Abstract
Spectrum power analysis in the low frequency oscillations (LFO) region of functional near infrared spectroscopy (fNIRS) is a promising method to deliver information about brain activation and therefore might be used for prognostication in patients with disorders of consciousness in the neurocritical care unit alongside with established methods. In this study, we measure the cortical hemodynamic response measured by fNIRS in the LFO region following auditory and somatosensory stimulation in healthy subjects. The significant hemodynamic reaction in the contralateral hemisphere correlation with the physiologic electric response suggests neurovascular coupling. In addition, we investigate power spectrum changes in steady state measurements of cerebral death patients and healthy subjects in the LFO region, the frequency of the heartbeat and respiration. The spectral power within the LFO region was lower in the patients with cerebral death compared to the healthy subjects, whereas there were no differences in spectral power for physiological activities such as heartbeat and respiration rate. This finding indicates the cerebral origin of our low frequency measurements. Therefore, LFO measurements are a potential method to detect brain activation in patients with disorders of consciousness and cerebral death. However, further studies in patients are needed to investigate its potential clinical use.
- Published
- 2024
7. Potential thresholds of critically increased cardiac-related spinal cord motion in degenerative cervical myelopathy.
- Author
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Pfender, Nikolai, Jutzeler, Catherine R., Hubli, Michèle, Scheuren, Paulina S., Pfyffer, Dario, Zipser, Carl M., Rosner, Jan, Friedl, Susanne, Sutter, Reto, Spirig, José M., Betz, Michael, Schubert, Martin, Seif, Maryam, Freund, Patrick, Farshad, Mazda, Curt, Armin, and Hupp, Markus
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SPINAL cord ,SPINAL cord diseases ,PHASE contrast magnetic resonance imaging ,SPINAL stenosis ,RECEIVER operating characteristic curves ,MYELOGRAPHY - Abstract
Introduction: New diagnostic techniques are a substantial research focus in degenerative cervical myelopathy (DCM). This cross-sectional study determined the significance of cardiac-related spinal cord motion and the extent of spinal stenosis as indicators of mechanical strain on the cord. Methods: Eighty-four DCM patients underwent MRI/clinical assessments and were classified as MRI+ [T2-weighted (T2w) hyperintense lesion in MRI] or MRI-(no T2w-hyperintense lesion). Cord motion (displacement assessed by phasecontrast MRI) and spinal stenosis [adapted spinal canal occupation ratio (aSCOR)] were related to neurological (sensory/motor) and neurophysiological readouts [contact heat evoked potentials (CHEPs)] by receiver operating characteristic (ROC) analysis. Results: MRI+ patients (N = 31; 36.9%) were more impaired compared to MRI-patients (N = 53; 63.1%) based on the modified Japanese Orthopedic Association (mJOA) subscores for upper {MRI+ [median (Interquartile range)]: 4 (4-5); MRI-: 5 (5-5); p < 0.01} and lower extremity [MRI+: 6 (6-7); MRI-: 7 (6-7); p = 0.03] motor dysfunction and the monofilament score [MRI+: 21 (18-23); MRI-: 24 (22-24); p < 0.01]. Both patient groups showed similar extent of cord motion and stenosis. Only in the MRI-group displacement identified patients with pathologic assessments [trunk/lower extremity pin prick score (T/LEPP): AUC = 0.67, p = 0.03; CHEPs: AUC = 0.73, p = 0.01]. Cord motion thresholds: T/LEPP: 1.67 mm (sensitivity 84.6%, specificity 52.5%); CHEPs: 1.96 mm (sensitivity 83.3%, specificity 65.6%). The aSCOR failed to show any relation to the clinical assessments. Discussion: These findings affirm cord motion measurements as a promising additional biomarker to improve the clinical workup and to enable timely surgical treatment particularly in MRI-DCM patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
8. Increased cranio-caudal spinal cord oscillations are the cardinal pathophysiological change in degenerative cervical myelopathy
- Author
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Pfender, Nikolai, primary, Rosner, Jan, additional, Zipser, Carl M., additional, Friedl, Susanne, additional, Schubert, Martin, additional, Sutter, Reto, additional, Klarhoefer, Markus, additional, Spirig, José M., additional, Betz, Michael, additional, Freund, Patrick, additional, Farshad, Mazda, additional, Curt, Armin, additional, and Hupp, Markus, additional
- Published
- 2023
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9. Cerebrospinal Fluid Pressure Dynamics as a Bedside Test in Traumatic Spinal Cord Injury to Assess Surgical Spinal Cord Decompression: Safety, Feasibility, and Proof-of-Concept
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Kheram, Najmeh, Boraschi, Andrea, Pfender, Nikolai, Friedl, Susanne Gabriele, Rasenack, Maria, Fritz, Benjamin, Kurtcuoglu, Vartan, Schubert, Martin, Curt, Armin, Zipser, Carl M, and University of Zurich
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spine surgery ,cerebrospinal fluid pressure ,spinal cord compression ,610 Medicine & health ,10046 Balgrist University Hospital, Swiss Spinal Cord Injury Center ,craniospinal compliance ,General Medicine ,spinal cord injury ,10052 Institute of Physiology ,compression biomarker - Abstract
Background Sufficient and timely spinal cord decompression is a critical surgical objective for neurological recovery in spinal cord injury (SCI). Residual cord compression may be associated with disturbed cerebrospinal fluid pressure (CSFP) dynamics. Objectives This study aims to assess whether intrathecal CSFP dynamics in SCI following surgical decompression are feasible and safe, and to explore the diagnostic utility. Methods Prospective cohort study. Bedside lumbar CSFP dynamics and cervical MRI were obtained following surgical decompression in N = 9 with mostly cervical acute-subacute SCI and N = 2 patients with non-traumatic SCI. CSFP measurements included mean CSFP, cardiac-driven CSFP peak-to-valley amplitudes (CSFPp), Valsalva maneuver, and Queckenstedt’s test (firm pressure on jugular veins, QT). From QT, proxies for cerebrospinal fluid pulsatility curve were calculated (ie, relative pulse pressure coefficient; RPPC-Q). CSFP metrics were compared to spine-healthy patients. computer tomography (CT)-myelography was done in 3/8 simultaneous to CSFP measurements. Results Mean age was 45 ± 9 years (range 17-67; 3F), SCI was complete (AIS A, N = 5) or incomplete (AIS B-D, N = 6). No adverse events related to CSFP assessments. CSFP rise during QT was induced in all patients [range 9.6-26.6 mmHg]. However, CSFPp was reduced in 3/11 (0.1-0.3 mmHg), and in 3/11 RPPC-Q was abnormal (0.01-0.05). Valsalva response was reduced in 8/11 (2.6-23.4 mmHg). CSFP dynamics corresponded to CT-myelography. Conclusions Comprehensive bedside lumbar CSFP dynamics in SCI following decompression are safe, feasible, and can reveal distinct patterns of residual spinal cord compression. Longitudinal studies are required to define critical thresholds of impaired CSFP dynamics that may impact neurological recovery and requiring surgical revisions.
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- 2023
10. Brainatwork: logging cognitive engagement and tasks in the workplace using electroencephalography.
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Mariam Hassib, Mohamed Khamis, Susanne Friedl, Stefan Schneegass, and Florian Alt
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- 2017
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11. TASCI—transcutaneous tibial nerve stimulation in patients with acute spinal cord injury to prevent neurogenic detrusor overactivity: protocol for a nationwide, randomised, sham-controlled, double-blind clinical trial
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Armin Curt, Martin W G Brinkhof, Xavier Jordan, Margret Hund-Georgiadis, Veronika Birkhäuser, Martina D Liechti, Collene E Anderson, Sarah Baumann, Michael Baumberger, Lori A Birder, Sander M Botter, Silvan Büeler, Célia D Cruz, Gergely David, Susanne Friedl, Oliver Gross, Knut Husmann, Miriam Koschorke, Lorenz Leitner, Eugenia Luca, Ulrich Mehnert, Sandra Möhr, Freschta Mohammadzada, Katia Monastyrskaya, Helen Sadri, Andrea M Sartori, Kai Sprengel, Stephanie A Stalder, Jivko Stoyanov, Cornelia Stress, Aurora Tatu, Cécile Tawadros, Stéphanie van der Lely, Jens Wöllner, Veronika Zubler, Jürgen Pannek, and Thomas M Kessler
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Medicine - Published
- 2020
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12. Increase in Low-Frequency Oscillations in fNIRS as Cerebral Response to Auditory Stimulation with Familiar Music
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Giulio Bicciato, Emanuela Keller, Martin Wolf, Giovanna Brandi, Sven Schulthess, Susanne Gabriele Friedl, Jan Folkard Willms, and Gagan Narula
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fNIRS ,music ,low-frequency oscillations ,LFO ,consciousness ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Recognition of typical patterns of brain response to external stimuli using near-infrared spectroscopy (fNIRS) may become a gateway to detecting covert consciousness in clinically unresponsive patients. This is the first fNIRS study on the cortical hemodynamic response to favorite music using a frequency domain approach. The aim of this study was to identify a possible marker of cognitive response in healthy subjects by investigating variations in the oscillatory signal of fNIRS in the spectral regions of low-frequency (LFO) and very-low-frequency oscillations (VLFO). The experiment consisted of two periods of exposure to preferred music, preceded and followed by a resting phase. Spectral power in the LFO region increased in all the subjects after the first exposure to music and decreased again in the subsequent resting phase. After the second music exposure, the increase in LFO spectral power was less distinct. Changes in LFO spectral power were more after first music exposure and the repetition-related habituation effect strongly suggest a cerebral origin of the fNIRS signal. Recognition of typical patterns of brain response to specific environmental stimulation is a required step for the concrete validation of a fNIRS-based diagnostic tool.
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- 2021
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13. In cervical spondylotic myelopathy spinal cord motion is focally increased at the level of stenosis: a controlled cross-sectional study
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Wolf, Katharina, Hupp, Markus, Friedl, Susanne, Sutter, Reto, Klarhöfer, Markus, Grabher, Patrick, Freund, Patrick, and Curt, Armin
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- 2018
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14. bTUNED : transcutaneous tibial nerve stimulation for neurogenic lower urinary tract
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Stalder, Stephanie A., primary, Gross, Oliver, additional, Anderson, Collene E., additional, Bachmann, Lucas M., additional, Baumann, Sarah, additional, Birkhäuser, Veronika, additional, Bywater, Mirjam, additional, del Popolo, Giulio, additional, Engeler, Daniel S., additional, Agrò, Enrico Finazzi, additional, Friedl, Susanne, additional, Grilo, Nuno, additional, Kiss, Stephan, additional, Koschorke, Miriam, additional, Leitner, Lorenz, additional, Liechti, Martina D., additional, Mehnert, Ulrich, additional, Musco, Stefania, additional, Sadri, Helen, additional, Stächele, Lara, additional, Tornic, Jure, additional, van der Lely, Stéphanie, additional, Wyler, Stephen, additional, and Kessler, Thomas M., additional
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- 2023
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15. Stability of the distal radioulnar joint with and without activation of forearm muscles
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Weber, Andreas, primary, Reissner, Lisa, additional, Friedl, Susanne, additional, and Schweizer, Andreas, additional
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- 2023
- Full Text
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16. Increased cranio-caudal spinal cord oscillations are the cardinal pathophysiological change in degenerative cervical myelopathy
- Author
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Pfender, Nikolai, Rosner, Jan, Zipser, Carl M, Friedl, Susanne, Schubert, Martin, Sutter, Reto, Klarhoefer, Markus, Spirig, José M, Betz, Michael, Freund, Patrick, Farshad, Mazda, Curt, Armin, Hupp, Markus, Pfender, Nikolai, Rosner, Jan, Zipser, Carl M, Friedl, Susanne, Schubert, Martin, Sutter, Reto, Klarhoefer, Markus, Spirig, José M, Betz, Michael, Freund, Patrick, Farshad, Mazda, Curt, Armin, and Hupp, Markus
- Abstract
INTRODUCTION Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic incomplete spinal cord injury, but its pathophysiology is poorly understood. As spinal cord compression observed in standard MRI often fails to explain a patient's status, new diagnostic techniques to assess DCM are one of the research priorities. Minor cardiac-related cranio-caudal oscillations of the cervical spinal cord are observed by phase-contrast MRI (PC-MRI) in healthy controls (HCs), while they become pathologically increased in patients suffering from degenerative cervical myelopathy. Whether transversal oscillations (i.e., anterior-posterior and right-left) also change in DCM patients is not known. METHODS We assessed spinal cord motion simultaneously in all three spatial directions (i.e., cranio-caudal, anterior-posterior, and right-left) using sagittal PC-MRI and compared physiological oscillations in 18 HCs to pathological changes in 72 DCM patients with spinal canal stenosis. The parameter of interest was the amplitude of the velocity signal (i.e., maximum positive to maximum negative peak) during the cardiac cycle. RESULTS Most patients suffered from mild DCM (mJOA score 16 (14-18) points), and the majority (68.1%) presented with multisegmental stenosis. The spinal canal was considerably constricted in DCM patients in all segments compared to HCs. Under physiological conditions in HCs, the cervical spinal cord oscillates in the cranio-caudal and anterior-posterior directions, while right-left motion was marginal [e.g., segment C5 amplitudes: cranio-caudal: 0.40 (0.27-0.48) cm/s; anterior-posterior: 0.18 (0.16-0.29) cm/s; right-left: 0.10 (0.08-0.13) cm/s]. Compared to HCs, DCM patients presented with considerably increased cranio-caudal oscillations due to the cardinal pathophysiologic change in non-stenotic [e.g., segment C5 amplitudes: 0.79 (0.49-1.32) cm/s] and stenotic segments [.g., segment C5 amplitudes: 0.99 (0.69-1.42) cm/s]). In contrast, right-left
- Published
- 2023
17. Stability of the distal radioulnar joint with and without activation of forearm muscles
- Author
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Weber, Andreas; https://orcid.org/0000-0002-2552-6653, Reissner, Lisa, Friedl, Susanne, Schweizer, Andreas, Weber, Andreas; https://orcid.org/0000-0002-2552-6653, Reissner, Lisa, Friedl, Susanne, and Schweizer, Andreas
- Abstract
The purpose of this study was to quantify the effect of the flexor carpi ulnaris and the extensor carpi ulnaris muscles on distal radioulnar joint stability. The anteroposterior ulnar head translation in relation to the radius was measured sonographically when the forearm was in a neutral resting position and when the hand was actively pressed on to a surface, with and without intentional flexor carpi ulnaris and extensor carpi ulnaris activation, while also being monitored by an electromyogram. Data on 40 healthy participants indicated a mean anteroposterior translation in the distal radioulnar joint of 4.1 mm (SD 1.08) without and 1.2 mm (SD 0.54) with muscle activation. Our results indicate that intentional ulnar forearm muscle activation results in 70% less anteroposterior ulnar head translation and greater distal radioulnar joint stability. Therefore, the flexor carpi ulnaris and extensor carpi ulnaris muscles serve as dynamic stabilizers of the distal radioulnar joint. This finding may be clinically significant since ulnar forearm muscles strengthening may increase distal radioulnar joint stability.
- Published
- 2023
18. bTUNED: transcutaneous tibial nerve stimulation for neurogenic lower urinary tract dysfunction
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Stalder, Stephanie A; https://orcid.org/0000-0002-7914-8264, Gross, Oliver; https://orcid.org/0000-0002-3330-5623, Anderson, Collene E; https://orcid.org/0000-0002-4350-6816, Bachmann, Lucas M; https://orcid.org/0000-0002-9868-154X, Baumann, Sarah, Birkhäuser, Veronika; https://orcid.org/0000-0002-6646-7266, Bywater, Mirjam, Del Popolo, Giulio; https://orcid.org/0000-0002-1202-6078, Engeler, Daniel S; https://orcid.org/0000-0003-1383-4701, Agrò, Enrico Finazzi; https://orcid.org/0000-0002-0308-8824, Friedl, Susanne; https://orcid.org/0000-0001-8686-8537, Grilo, Nuno; https://orcid.org/0000-0002-7188-972X, Kiss, Stephan, Koschorke, Miriam; https://orcid.org/0000-0001-5667-0474, Leitner, Lorenz; https://orcid.org/0000-0001-5764-3494, Liechti, Martina D; https://orcid.org/0000-0002-3024-0975, Mehnert, Ulrich; https://orcid.org/0000-0001-7963-8477, Musco, Stefania; https://orcid.org/0000-0001-5844-5684, Sadri, Helen, Stächele, Lara; https://orcid.org/0000-0002-9723-0595, Tornic, Jure; https://orcid.org/0000-0002-1831-4783, van der Lely, Stéphanie; https://orcid.org/0000-0002-2688-9042, Wyler, Stephen, Kessler, Thomas M; https://orcid.org/0000-0002-1991-5919, Stalder, Stephanie A; https://orcid.org/0000-0002-7914-8264, Gross, Oliver; https://orcid.org/0000-0002-3330-5623, Anderson, Collene E; https://orcid.org/0000-0002-4350-6816, Bachmann, Lucas M; https://orcid.org/0000-0002-9868-154X, Baumann, Sarah, Birkhäuser, Veronika; https://orcid.org/0000-0002-6646-7266, Bywater, Mirjam, Del Popolo, Giulio; https://orcid.org/0000-0002-1202-6078, Engeler, Daniel S; https://orcid.org/0000-0003-1383-4701, Agrò, Enrico Finazzi; https://orcid.org/0000-0002-0308-8824, Friedl, Susanne; https://orcid.org/0000-0001-8686-8537, Grilo, Nuno; https://orcid.org/0000-0002-7188-972X, Kiss, Stephan, Koschorke, Miriam; https://orcid.org/0000-0001-5667-0474, Leitner, Lorenz; https://orcid.org/0000-0001-5764-3494, Liechti, Martina D; https://orcid.org/0000-0002-3024-0975, Mehnert, Ulrich; https://orcid.org/0000-0001-7963-8477, Musco, Stefania; https://orcid.org/0000-0001-5844-5684, Sadri, Helen, Stächele, Lara; https://orcid.org/0000-0002-9723-0595, Tornic, Jure; https://orcid.org/0000-0002-1831-4783, van der Lely, Stéphanie; https://orcid.org/0000-0002-2688-9042, Wyler, Stephen, and Kessler, Thomas M; https://orcid.org/0000-0002-1991-5919
- Abstract
OBJECTIVE To present the protocol for a randomized controlled trial (RCT) evaluating the efficacy and safety of transcutaneous tibial nerve stimulation (TTNS) for refractory neurogenic lower urinary tract dysfunction (NLUTD). STUDY DESIGN AND RESULTS bTUNED (bladder and TranscUtaneous tibial Nerve stimulation for nEurogenic lower urinary tract Dysfunction) is an international multicentre, sham-controlled, double-blind RCT investigating the efficacy and safety of TTNS. The primary outcome is success of TTNS, defined as improvements in key bladder diary variables at study end compared to baseline values. The focus of the treatment is defined by the Self-Assessment Goal Achievement (SAGA) questionnaire. Secondary outcomes are the effect of TTNS on urodynamic, neurophysiological, and bowel function outcome measures, as well as the safety of TTNS. CONCLUSIONS A total of 240 patients with refractory NLUTD will be included and randomized 1:1 into the verum or sham TTNS group from March 2020 until August 2026. TTNS will be performed twice a week for 30 min during 6 weeks. The patients will attend baseline assessments, 12 treatment visits and follow-up assessments at the study end.
- Published
- 2023
19. <scp>bTUNED</scp> : transcutaneous tibial nerve stimulation for neurogenic lower urinary tract
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Stephanie A. Stalder, Oliver Gross, Collene E. Anderson, Lucas M. Bachmann, Sarah Baumann, Veronika Birkhäuser, Mirjam Bywater, Giulio del Popolo, Daniel S. Engeler, Enrico Finazzi Agrò, Susanne Friedl, Nuno Grilo, Stephan Kiss, Miriam Koschorke, Lorenz Leitner, Martina D. Liechti, Ulrich Mehnert, Stefania Musco, Helen Sadri, Lara Stächele, Jure Tornic, Stéphanie van der Lely, Stephen Wyler, and Thomas M. Kessler
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Urology - Published
- 2023
20. bTUNED: transcutaneous tibial nerve stimulation for neurogenic lower urinary tract dysfunction
- Author
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Stalder, Stephanie A, Gross, Oliver, Anderson, Collene E, Bachmann, Lucas M, Baumann, Sarah, Birkhäuser, Veronika, Bywater, Mirjam, Del Popolo, Giulio, Engeler, Daniel S, Agrò, Enrico Finazzi, Friedl, Susanne, Grilo, Nuno, Kiss, Stephan, Koschorke, Miriam, Leitner, Lorenz, Liechti, Martina D, Mehnert, Ulrich, Musco, Stefania, Sadri, Helen, Stächele, Lara, Tornic, Jure, van der Lely, Stéphanie, Wyler, Stephen, Kessler, Thomas M, and University of Zurich
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610 Medicine & health ,10046 Balgrist University Hospital, Swiss Spinal Cord Injury Center - Published
- 2023
- Full Text
- View/download PDF
21. Comparison of axial and sagittal spinal cord motion measurements in degenerative cervical myelopathy
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Pfender, Nikolai, Rosner, Jan, Zipser, Carl Moritz, Friedl, Susanne, Vallotton, Kevin, Sutter, Reto, Klarhoefer, Markus, Schubert, Martin, Betz, Michael, Spirig, José Miguel, Seif, Maryam, Hubli, Michèle, Freund, Patrick, Farshad, Mazda, Curt, Armin, Hupp, Markus, University of Zurich, and Hupp, Markus
- Subjects
610 Medicine & health ,Magnetic Resonance Imaging ,Spinal Cord Diseases ,2728 Neurology (clinical) ,Spinal Cord ,Cervical Vertebrae ,Humans ,2741 Radiology, Nuclear Medicine and Imaging ,Radiology, Nuclear Medicine and imaging ,10046 Balgrist University Hospital, Swiss Spinal Cord Injury Center ,Neurology (clinical) ,Spinal Cord Compression ,Neck - Abstract
Background and purpose: The timing of decision-making for a surgical intervention in patients with mild degenerative cervical myelopathy (DCM) is challenging. Spinal cord motion phase contrast MRI (PC-MRI) measurements can reveal the extent of dynamic mechanical strain on the spinal cord to potentially identify high-risk patients. This study aims to determine the comparability of axial and sagittal PC-MRI measurements of spinal cord motion with the prospect of improving the clinical workup.Methods: Sixty-four DCM patients underwent a PC-MRI scan assessing spinal cord motion. The agreement of axial and sagittal measurements was determined by means of intraclass correlation coefficients (ICCs) and Bland-Altman analyses.Results: The comparability of axial and sagittal PC-MRI measurements was good to excellent at all cervical levels (ICCs motion amplitude: .810-.940; p < .001). Significant differences between axial and sagittal amplitude values could be found at segments C3 and C4, while its magnitude was low (C3: 0.07 ± 0.19 cm/second; C4: -0.12 ± 0.30 cm/second). Bland-Altman analysis showed a good agreement between axial and sagittal PC-MRI scans (coefficients of repeatability: minimum -0.23 cm/second at C2; maximum -0.58 cm/second at C4). Subgroup analysis regarding anatomic conditions (stenotic vs. nonstenotic segments) and different velocity encoding (2 vs. 3 cm/second) showed comparable results.Conclusions: This study demonstrates good comparability between axial and sagittal spinal cord motion measurements in DCM patients. To this end, axial and sagittal PC-MRI are both accurate and sensitive in detecting pathologic cord motion. Therefore, such measures could identify high-risk patients and improve clinical decision-making (ie, timing of decompression).
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- 2022
22. Comparison of axial and sagittal spinal cord motion measurements in degenerative cervical myelopathy
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Pfender, Nikolai, primary, Rosner, Jan, additional, Zipser, Carl Moritz, additional, Friedl, Susanne, additional, Vallotton, Kevin, additional, Sutter, Reto, additional, Klarhoefer, Markus, additional, Schubert, Martin, additional, Betz, Michael, additional, Spirig, José Miguel, additional, Seif, Maryam, additional, Hubli, Michèle, additional, Freund, Patrick, additional, Farshad, Mazda, additional, Curt, Armin, additional, and Hupp, Markus, additional
- Published
- 2022
- Full Text
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23. Stability of the distal radioulnar joint with and without activation of forearm muscles
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Andreas Weber, Lisa Reissner, Susanne Friedl, and Andreas Schweizer
- Subjects
Surgery - Abstract
The purpose of this study was to quantify the effect of the flexor carpi ulnaris and the extensor carpi ulnaris muscles on distal radioulnar joint stability. The anteroposterior ulnar head translation in relation to the radius was measured sonographically when the forearm was in a neutral resting position and when the hand was actively pressed on to a surface, with and without intentional flexor carpi ulnaris and extensor carpi ulnaris activation, while also being monitored by an electromyogram. Data on 40 healthy participants indicated a mean anteroposterior translation in the distal radioulnar joint of 4.1 mm (SD 1.08) without and 1.2 mm (SD 0.54) with muscle activation. Our results indicate that intentional ulnar forearm muscle activation results in 70% less anteroposterior ulnar head translation and greater distal radioulnar joint stability. Therefore, the flexor carpi ulnaris and extensor carpi ulnaris muscles serve as dynamic stabilizers of the distal radioulnar joint. This finding may be clinically significant since ulnar forearm muscles strengthening may increase distal radioulnar joint stability.
- Published
- 2023
24. Functional NIRS to detect covert consciousness in neurocritical patients
- Author
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Bicciato, Giulio; https://orcid.org/0000-0002-2956-0189, Narula, Gagan; https://orcid.org/0000-0002-7445-3710, Brandi, Giovanna; https://orcid.org/0000-0002-6682-2424, Eisele, Amanda, Schulthess, Sven; https://orcid.org/0000-0002-1786-1670, Friedl, Susanne; https://orcid.org/0000-0001-8686-8537, Willms, Jan Folkard, Westphal, Laura P; https://orcid.org/0000-0002-8373-3132, Keller, Emanuela; https://orcid.org/0000-0002-7560-7574, Bicciato, Giulio; https://orcid.org/0000-0002-2956-0189, Narula, Gagan; https://orcid.org/0000-0002-7445-3710, Brandi, Giovanna; https://orcid.org/0000-0002-6682-2424, Eisele, Amanda, Schulthess, Sven; https://orcid.org/0000-0002-1786-1670, Friedl, Susanne; https://orcid.org/0000-0001-8686-8537, Willms, Jan Folkard, Westphal, Laura P; https://orcid.org/0000-0002-8373-3132, and Keller, Emanuela; https://orcid.org/0000-0002-7560-7574
- Abstract
Objective This pilot study assesses the feasibility to detect covert consciousness in clinically unresponsive patients by means of functional near infrared spectroscopy (fNIRS) in a real intensive care unit setting. We aimed to verify if the hemodynamic response to familiar music measured with fNIRS varies according to the level consciousness of the patients. Methods 22 neurocritical patients and 6 healthy controls were included. The experiment consisted in 3 subsequent blocks including a first resting state recording, a period of music playback and a second resting state recording. fNIRS measurement were performed on each subject with two optodes on the forehead. Main oscillatory frequencies of oxyhemoglobin signal were analyzed. Spectral changes of low frequency oscillations (LFO) between subsequent experimental blocks were used as a marker of cortical response. Cortical response was compared to the level of consciousness of the patients and their functional outcome, through validated clinical scores. Results Cortical hemodynamic response to music on the left prefrontal brain was associated with the level of consciousness of the patients and with their clinical outcome after three months. Conclusions Variations in LFO spectral power measured with fNIRS may be a new marker of cortical responsiveness to detect covert consciousness in neurocritical patients. Left prefrontal cortex may play an important role in the perception of familiar music. Significance We showed the feasibility of a simple fNIRS approach to detect cortical response in the real setting of an intensive care unit.
- Published
- 2022
25. Increase in Low-Frequency Oscillations in fNIRS as Cerebral Response to Auditory Stimulation with Familiar Music
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Bicciato, Giulio, Keller, Emanuela, Wolf, Martin, Brandi, Giovanna, Schulthess, Sven, Friedl, Susanne Gabriele, Willms, Jan, Narula, Gagan, University of Zurich, and Bicciato, Giulio
- Subjects
low-frequency oscillations ,General Neuroscience ,LFO ,2800 General Neuroscience ,Neurosciences. Biological psychiatry. Neuropsychiatry ,fNIRS ,610 Medicine & health ,music ,consciousness ,10027 Clinic for Neonatology ,Article ,10040 Clinic for Neurology ,10180 Clinic for Neurosurgery ,10023 Institute of Intensive Care Medicine ,RC321-571 - Abstract
Recognition of typical patterns of brain response to external stimuli using near-infrared spectroscopy (fNIRS) may become a gateway to detecting covert consciousness in clinically unresponsive patients. This is the first fNIRS study on the cortical hemodynamic response to favorite music using a frequency domain approach. The aim of this study was to identify a possible marker of cognitive response in healthy subjects by investigating variations in the oscillatory signal of fNIRS in the spectral regions of low-frequency (LFO) and very-low-frequency oscillations (VLFO). The experiment consisted of two periods of exposure to preferred music, preceded and followed by a resting phase. Spectral power in the LFO region increased in all the subjects after the first exposure to music and decreased again in the subsequent resting phase. After the second music exposure, the increase in LFO spectral power was less distinct. Changes in LFO spectral power were more after first music exposure and the repetition-related habituation effect strongly suggest a cerebral origin of the fNIRS signal. Recognition of typical patterns of brain response to specific environmental stimulation is a required step for the concrete validation of a fNIRS-based diagnostic tool.
- Published
- 2021
26. Increase in Low-Frequency Oscillations in fNIRS as Cerebral Response to Auditory Stimulation with Familiar Music
- Author
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Bicciato, Giulio, primary, Keller, Emanuela, additional, Wolf, Martin, additional, Brandi, Giovanna, additional, Schulthess, Sven, additional, Friedl, Susanne Gabriele, additional, Willms, Jan Folkard, additional, and Narula, Gagan, additional
- Published
- 2021
- Full Text
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27. TASCI-transcutaneous tibial nerve stimulation in patients with acute spinal cord injury to prevent neurogenic detrusor overactivity: protocol for a nationwide, randomised, sham-controlled, double-blind clinical trial
- Author
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Birkhäuser, Veronika, Liechti, Martina D, Anderson, Collene E, Bachmann, Lucas M, Baumann, Sarah, Baumberger, Michael, Birder, Lori A, Botter, Sander M, Büeler, Silvan, Cruz, Célia D, David, Gergely, Freund, Patrick, Friedl, Susanne, Gross, Oliver, Hund-Georgiadis, Margret, Husmann, Knut, Jordan, Xavier, Koschorke, Miriam, Leitner, Lorenz, Luca, Eugenia, Mehnert, Ulrich, Möhr, Sandra, Mohammadzada, Freschta, Monastyrskaya, Katia, Pfender, Nikolai, Pohl, Daniel, Sadri, Helen, Sartori, Andrea M, Schubert, Martin, Sprengel, Kai, et al, and University of Zurich
- Subjects
10021 Department of Trauma Surgery ,10219 Clinic for Gastroenterology and Hepatology ,610 Medicine & health ,10046 Balgrist University Hospital, Swiss Spinal Cord Injury Center ,11359 Institute for Regenerative Medicine (IREM) ,2700 General Medicine - Published
- 2020
28. The Damaged Spinal Cord Is a Suitable Target for Stem Cell Transplantation
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Kan Min, Reto Sutter, Rudolf P. Wüthrich, Armin Curt, Martin Schubert, Raphael Guzman, Dario Pfyffer, Steve Casha, Catherine R. Jutzeler, Evenline Huber, Markus Hupp, Susanne Friedl, Michael G. Fehlings, Jane Hsieh, Patrick Freund, University of Zurich, and Curt, Armin
- Subjects
Oncology ,Adult ,Male ,030506 rehabilitation ,medicine.medical_specialty ,Cord ,medicine.medical_treatment ,Population ,610 Medicine & health ,Thoracic Vertebrae ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Neural Stem Cells ,Internal medicine ,medicine ,Humans ,10035 Clinic for Nephrology ,education ,Spinal cord injury ,Spinal Cord Injuries ,education.field_of_study ,business.industry ,Process Assessment, Health Care ,Immunosuppression ,General Medicine ,Middle Aged ,medicine.disease ,Spinal cord ,Transplantation ,2742 Rehabilitation ,medicine.anatomical_structure ,2728 Neurology (clinical) ,2808 Neurology ,Feasibility Studies ,Female ,10046 Balgrist University Hospital, Swiss Spinal Cord Injury Center ,Stem cell ,0305 other medical science ,business ,030217 neurology & neurosurgery ,Adult stem cell ,Follow-Up Studies ,Stem Cell Transplantation - Abstract
Background. Given individuals with spinal cord injury (SCI) approaching 2 million, viable options for regenerative repair are desperately needed. Human central nervous system stem cells (HuCNS-SC) are self-renewing, multipotent adult stem cells that engraft, migrate, and differentiate in appropriate regions in multiple animal models of injured brain and spinal cord. Preclinical improved SCI locomotor function provided rationale for the first-in-human SCI clinical trial of HuCNS-SC cells. Evidence of feasibility and long-term safety of cell transplantation into damaged human cord is needed to foster translational progression of cellular therapies. Methods. A first-ever, multisite phase I/IIa trial involving surgical transplantation of 20 million HuCNS-SC cells into the thoracic cord in 12 AIS A or B subjects (traumatic, T2-T11 motor-complete, sensory-incomplete), aged 19 to 53 years, demonstrated safety and preliminary efficacy. Six-year follow-up data were collected (sensory thresholds and neuroimaging augmenting clinical assessments). Findings. The study revealed short- and long-term surgical and medical safety (well-tolerated immunosuppression in population susceptible to infections). Preliminary efficacy measures identified 5/12 with reliable sensory improvements. Unfortunately, without thoracic muscles available for manual muscle examination, thoracic motor changes could not be measured. Lower limb motor scores did not change during the study. Cervical cord imaging revealed, no tumor formation or malformation of the lesion area, and secondary supralesional structural changes similar to SCI control subjects. Interpretation. Short- and long-term safety and feasibility support the consideration of cell transplantation for patients with complete and incomplete SCI. This report is an important step to prepare, foster, and maintain the therapeutic development of cell transplantation for human SCI.
- Published
- 2020
29. TASCI-transcutaneous tibial nerve stimulation in patients with acute spinal cord injury to prevent neurogenic detrusor overactivity: protocol for a nationwide, randomised, sham-controlled, double-blind clinical trial
- Author
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Birkhäuser, Veronika; https://orcid.org/0000-0002-6646-7266, Liechti, Martina D; https://orcid.org/0000-0002-3024-0975, Anderson, Collene E; https://orcid.org/0000-0002-4350-6816, Bachmann, Lucas M, Baumann, Sarah, Baumberger, Michael, Birder, Lori A, Botter, Sander M, Büeler, Silvan, Cruz, Célia D, David, Gergely; https://orcid.org/0000-0002-9379-5193, Freund, Patrick, Friedl, Susanne, Gross, Oliver, Hund-Georgiadis, Margret, Husmann, Knut, Jordan, Xavier, Koschorke, Miriam, Leitner, Lorenz, Luca, Eugenia, Mehnert, Ulrich; https://orcid.org/0000-0001-7963-8477, Möhr, Sandra, Mohammadzada, Freschta, Monastyrskaya, Katia, Pfender, Nikolai, Pohl, Daniel; https://orcid.org/0000-0002-0855-1152, Sadri, Helen, Sartori, Andrea M; https://orcid.org/0000-0002-9571-0288, Schubert, Martin, Sprengel, Kai, et al, Birkhäuser, Veronika; https://orcid.org/0000-0002-6646-7266, Liechti, Martina D; https://orcid.org/0000-0002-3024-0975, Anderson, Collene E; https://orcid.org/0000-0002-4350-6816, Bachmann, Lucas M, Baumann, Sarah, Baumberger, Michael, Birder, Lori A, Botter, Sander M, Büeler, Silvan, Cruz, Célia D, David, Gergely; https://orcid.org/0000-0002-9379-5193, Freund, Patrick, Friedl, Susanne, Gross, Oliver, Hund-Georgiadis, Margret, Husmann, Knut, Jordan, Xavier, Koschorke, Miriam, Leitner, Lorenz, Luca, Eugenia, Mehnert, Ulrich; https://orcid.org/0000-0001-7963-8477, Möhr, Sandra, Mohammadzada, Freschta, Monastyrskaya, Katia, Pfender, Nikolai, Pohl, Daniel; https://orcid.org/0000-0002-0855-1152, Sadri, Helen, Sartori, Andrea M; https://orcid.org/0000-0002-9571-0288, Schubert, Martin, Sprengel, Kai, and et al
- Abstract
INTRODUCTION: Neurogenic lower urinary tract dysfunction (NLUTD), including neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia, is one of the most frequent and devastating sequelae of spinal cord injury (SCI), as it can lead to urinary incontinence and secondary damage such as renal failure. Transcutaneous tibial nerve stimulation (TTNS) is a promising, non-invasive neuromodulatory intervention that may prevent the emergence of the C-fibre evoked bladder reflexes that are thought to cause NDO. This paper presents the protocol for TTNS in acute SCI (TASCI), which will evaluate the efficacy of TTNS in preventing NDO. Furthermore, TASCI will provide insight into the mechanisms underlying TTNS, and the course of NLUTD development after SCI. METHODS AND ANALYSIS: TASCI is a nationwide, randomised, sham-controlled, double-blind clinical trial, conducted at all four SCI centres in Switzerland. The longitudinal design includes a baseline assessment period 5-39 days after acute SCI and follow-up assessments occurring 3, 6 and 12 months after SCI. A planned 114 participants will be randomised into verum or sham TTNS groups (1:1 ratio), stratified on study centre and lower extremity motor score. TTNS is performed for 30 min/day, 5 days/week, for 6-9 weeks starting within 40 days after SCI. The primary outcome is the occurrence of NDO jeopardising the upper urinary tract at 1 year after SCI, assessed by urodynamic investigation. Secondary outcome measures assess bladder and bowel function and symptoms, sexual function, neurological structure and function, functional independence, quality of life, as well as changes in biomarkers in the urine, blood, stool and bladder tissue. Safety of TTNS is the tertiary outcome. ETHICS AND DISSEMINATION: TASCI is approved by the Swiss Ethics Committee for Northwest/Central Switzerland, the Swiss Ethics Committee Vaud and the Swiss Ethics Committee Zürich (#2019-00074). Findings will be disseminated through peer-reviewed
- Published
- 2020
30. TASCI—transcutaneous tibial nerve stimulation in patients with acute spinal cord injury to prevent neurogenic detrusor overactivity: protocol for a nationwide, randomised, sham-controlled, double-blind clinical trial
- Author
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Birkhäuser, Veronika, primary, Liechti, Martina D, additional, Anderson, Collene E, additional, Bachmann, Lucas M, additional, Baumann, Sarah, additional, Baumberger, Michael, additional, Birder, Lori A, additional, Botter, Sander M, additional, Büeler, Silvan, additional, Cruz, Célia D, additional, David, Gergely, additional, Freund, Patrick, additional, Friedl, Susanne, additional, Gross, Oliver, additional, Hund-Georgiadis, Margret, additional, Husmann, Knut, additional, Jordan, Xavier, additional, Koschorke, Miriam, additional, Leitner, Lorenz, additional, Luca, Eugenia, additional, Mehnert, Ulrich, additional, Möhr, Sandra, additional, Mohammadzada, Freschta, additional, Monastyrskaya, Katia, additional, Pfender, Nikolai, additional, Pohl, Daniel, additional, Sadri, Helen, additional, Sartori, Andrea M, additional, Schubert, Martin, additional, Sprengel, Kai, additional, Stalder, Stephanie A, additional, Stoyanov, Jivko, additional, Stress, Cornelia, additional, Tatu, Aurora, additional, Tawadros, Cécile, additional, van der Lely, Stéphanie, additional, Wöllner, Jens, additional, Zubler, Veronika, additional, Curt, Armin, additional, Pannek, Jürgen, additional, Brinkhof, Martin W G, additional, and Kessler, Thomas M, additional
- Published
- 2020
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31. The Damaged Spinal Cord Is a Suitable Target for Stem Cell Transplantation
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Curt, Armin, primary, Hsieh, Jane, additional, Schubert, Martin, additional, Hupp, Markus, additional, Friedl, Susanne, additional, Freund, Patrick, additional, Huber, Evenline, additional, Pfyffer, Dario, additional, Sutter, Reto, additional, Jutzeler, Catherine, additional, Wüthrich, Rudolf P., additional, Min, Kan, additional, Casha, Steve, additional, Fehlings, Michael G., additional, and Guzman, Raphael, additional
- Published
- 2020
- Full Text
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32. The Human Spinal Cord is a Promising Target for Allogeneic Neural Stem Cell Transplantation
- Author
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Steven Casha, Martin Schubert, Reto Sutter, Rudolf P. Wüthrich, Dario Pfyffer, Eveline Huber, Catherine R. Jutzeler, Jane Hsieh, Kan Min, Susanne Friedl, Armin Curt, Patrick Freund, Markus Hupp, Michael G. Fehlings, and Raphael Guzman
- Subjects
Sensory function ,Transplantation ,Safety profile ,medicine.anatomical_structure ,business.industry ,Medicine ,business ,Spinal cord ,medicine.disease ,Neuroscience ,Spinal cord injury ,Neural stem cell - Abstract
This report documents the first-in-man investigational trial and long-term follow-up of HuCNS-SC transplantation in chronic SCI. The small study size and open-label design reflect the pilot nature of this investigation, and the focus on determining feasibility, safety and preliminary efficacy. Based on the short- and long-term safety profile established in this study for individuals with thoracic SCI, a larger-scale, randomized, study in people with cervical SCI was approved in the US. These trials have established that the human spinal cord is a promising target for neural stem cell transplantation.
- Published
- 2019
33. Safety and Preliminary Efficacy of Allogeneic Neural Stem Cell Transplantation in Chronic Spinal Cord Injury: A Translational Phase I/IIa Trial
- Author
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Eveline Huber, Raphael Guzman, Armin Curt, Michael G. Fehlings, Reto Sutter, Rudolf P. Wüthrich, Markus Hupp, Martin Schubert, Kan Min, Steven Casha, Jane Hsieh, Dario Pfyffer, Susanne Friedl, Catherine R. Jutzeler, and Patrick Freund
- Subjects
medicine.medical_specialty ,business.industry ,medicine.disease ,Site Investigator ,Clinical trial ,Transplantation ,Protocol design ,medicine ,Physical therapy ,Neurosurgery ,business ,Paraplegia ,Spinal cord injury ,Declaration of Helsinki - Abstract
Background: Given the large number of individuals living with disabling sensorimotor impairment due to spinal cord injury (SCI) approaching 2 million, viable options for regenerative repair strategies of the injured spinal cord are desperately needed. Human central nervous system stem cells (HuCNS-SC®) are self-renewing, multi-potent adult stem cells exhibiting successful engraftment, migration, and region-appropriate differentiation as demonstrated in multiple animal models for the injured brain and spinal cord. In preclinical SCI models, improved locomotor function provided the rationale for the first human thoracic SCI clinical trial of HuCNS-SC cells. Methods: Safety and preliminary efficacy data were collected within a first ever multi-site phase I/IIa trial involving surgical transplantation of 20 million HuCNS-SC cells into the thoracic cord in 12 subjects with sensory or motor complete traumatic paraplegia. Up to 6 years follow-up data was collected applying an extended protocol design augmenting clinical assessments through corroborating measures of sensory thresholds and neuroimaging to improve readouts of safety and efficacy. Findings: The study revealed promising short and long term surgical and medical safety. Measures of preliminary efficacy could discern responders (5/12 patients) with reliable improvements in sensory function albeit without measurable motor changes in thoracic injuries. Imaging of the spinal cord at and rostral the site of injection revealed dynamic structural changes similar to findings in non-transplanted SCI subjects. Interpretation: Findings of safety and feasibility supported the regulatory approval for a Phase II HuCNS-SC transplantation study in cervical spinal cord injured patients. Funding: The initial study (short term follow-up of the first year; STFU) and part of the second study (long term follow-up; LTFU) was funded by Stem Cells Inc, Newark, California, USA. After dissolution of Stem Cells Inc. Q3 2016 grants from Wings for Life (WfL), and the Bright Oceans Corporation (BOCO) enabled completion of the LTFU, compilation of the full set of monitored data (initial Phase I/IIa STFU trial and LTFU study), data analysis and manuscript completion. Declaration of Interest: Armin Curt has no competing interests. Principal Investigator for multi-site Phase I/IIa trial of 12 subjects and primary author (corresponding author). Jane Hsieh, with no competing interests, is an independent consultant to the Spinal Cord Injury Center Balgrist initiating data analysis and the first draft of the manuscript, as well as coordinating contributions from collaborating authors. Martin Schubert with no competing interests, participated in care of 9 enrolled subjects, data analysis and review of manuscript. Markus Hupp has no competing interests. Participated in the care of 9 enrolled subjects and reviewed the manuscript. Susi Friedl has no competing interests. Participated in the care of 9 enrolled subjects and reviewed the manuscript. Patrick Freund has no competing interests. Collected and analyzed neuroimaging data for 9 enrolled subjects and reviewed the manuscript. Eveline Huber has no competing interests. Collected and analyzed neuroimaging data for 9 enrolled subjects and reviewed the manuscript. Dario Pfyffer has no competing interests. Collected and analyzed neuroimaging data for 9 enrolled subjects, assisted with figure creation and reviewed the manuscript. Safety of neural stem cell transplantation into the human spinal cord Draft version: V6.1 20190128 Reto Sutter has no competing interests. Collected and analysed neuroimaging data for 9 enrolled subjects and reviewed the manuscript. Catherine Jutzeler has no competing interests. Collected and analysed electrophysiological data for 9 enrolled subjects and reviewed the manuscript. Rudolf P. Wuthrich has no competing interests. Provided immunosuppression for 9 enrolled subjects and reviewed the manuscript. Kan Min has no competing conflicts of interest. Performed orthopaedic spinal surgery for 9 HuCNS-SC transplantations at Balgrist site and reviewed the manuscript. Steve Casha has no competing interests. Site investigator at University of Calgary with 2 patients enrolled and transplanted, and reviewed the manuscript. Michael Fehlings has no competing interests. Site investigator at University of Toronto with 1 patient enrolled and transplanted, and reviewed the manuscript. Raphael Guzmann has no competing interests. Performed neurosurgery and HuCNS-SC transplantation for 9 enrolled subjects and reviewed the manuscript. Ethical Approval: The study protocol and all amendments were approved by related Ethics Committees and regulatory agencies in accordance with the Declaration of Helsinki.
- Published
- 2019
34. RECONSTRUCTION OF EYE CLOSURE BY MUSCLE TRANSPOSITION OR MUSCLE TRANSPLANTATION IN FACIAL PALSY: FP421
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Frey, Manfred, Giovanoli, Pietro, john Tzou, Chieh-han, Kropf, Nina, and Friedl, Susanne
- Published
- 2003
35. In cervical spondylotic myelopathy spinal cord motion is focally increased at the level of stenosis: a controlled cross-sectional study
- Author
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Reto Sutter, Armin Curt, Katharina Wolf, Markus Klarhöfer, Susanne Friedl, Markus Hupp, Patrick Freund, Patrick Grabher, University of Zurich, and Wolf, Katharina
- Subjects
Male ,medicine.medical_specialty ,Neurology ,Clinical Neurology ,610 Medicine & health ,Constriction, Pathologic ,030218 nuclear medicine & medical imaging ,Constriction ,03 medical and health sciences ,Motion ,0302 clinical medicine ,Cerebrospinal fluid ,Sex Factors ,Internal medicine ,medicine ,Humans ,Spinal canal ,Prospective Studies ,Prospective cohort study ,Cerebrospinal Fluid ,medicine.diagnostic_test ,business.industry ,Age Factors ,Cervical Cord ,Magnetic resonance imaging ,General Medicine ,Middle Aged ,medicine.disease ,Spinal cord ,Magnetic Resonance Imaging ,Stenosis ,medicine.anatomical_structure ,Cross-Sectional Studies ,2728 Neurology (clinical) ,2808 Neurology ,Cardiology ,Cervical Vertebrae ,Linear Models ,Female ,10046 Balgrist University Hospital, Swiss Spinal Cord Injury Center ,Neurology (clinical) ,Spondylosis ,business ,030217 neurology & neurosurgery - Abstract
Level-, age-, and gender-matched controlled cross-sectional cohort study. To investigate alterations of spinal cord (SC) motion within cervical spondylotic myelopathy (CSM) across the cervical spinal segments and its relation to cerebrospinal fluid (CSF)-flow, anatomic conditions, and clinical parameters. University Hospital Balgrist, Zurich, Switzerland. Overall, 12 patients suffering from CSM at level C5 and 12 controls underwent cardiac-gated 2D phase-contrast-MRI at level C2 and C5 and standard MRI sequences. Parameters of interest: Velocity measurements of SC and CSF (area under the curve = total displacement (normalization for duration of the heart cycle), total displacement ratio (C5/C2; intraindividual normalization for confounders)), spinal canal diameters, clinical motor- and sensory scores, and performance measures. Interrater reliability was excellent for SC motion at both levels and for CSF flow at C2, but not reliable for CSF flow at C5. Within controls, SC motion at C2 positively correlated with SC motion at C5 (p = 0.000); this correlation diminished in patients (p = 0.860). SC total displacement ratio was significantly increased in patients (p = 0.029) and correlated with clinical impairment (p = 0.017). Morphometric measures of the extent of stenosis were not related to SC motion or clinical symptoms. The findings revealed physiological interactions of CSF flow and SC motion across the cervical spine in healthy controls while being diminished in CSM patients. Findings of focally increased SC motion at the level of stenosis were related to clinical impairment and might be promising as a diagnostic and prognostic marker in CSM. CRPP Neurorehab of the University of Zurich, Switzerland.
- Published
- 2018
36. Safety and Preliminary Efficacy of Allogeneic Neural Stem Cell Transplantation in Chronic Spinal Cord Injury: A Translational Phase I/IIa Trial
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Curt, Armin, primary, Hsieh, Jane, additional, Schubert, Martin, additional, Hupp, Markus, additional, Friedl, Susanne, additional, Freund, Patrick, additional, Huber, Eveline, additional, Pfyffer, Dario, additional, Sutter, Reto, additional, Jutzeler, Catherine, additional, Wüthrich, R. P., additional, Min, Kan, additional, Casha, Steven, additional, Fehlings, Michael, additional, and Guzman, Raphael, additional
- Published
- 2019
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37. The Human Spinal Cord is a Promising Target for Allogeneic Neural Stem Cell Transplantation
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Curt, Armin, primary, Hsieh, Jane, additional, Schubert, Martin, additional, Hupp, Markus, additional, Friedl, Susanne, additional, Freund, Patrick, additional, Huber, Eveline, additional, Pfyffer, Dario, additional, Sutter, Reto, additional, Jutzeler, Catherine, additional, Wüthrich, R.P., additional, Min, K., additional, Casha, S., additional, Fehlings, M.G., additional, and Guzman, Raphael, additional
- Published
- 2019
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38. Quantification of 1,8-Cineole in Human Blood and Plasma and the Impact of Liner Choice in Head-Space Chromatography
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Susanne Friedl, Eva Heuberger, Katharina Oedendorfer, Simone Kitzer, Lejla Jaganjac, Iris Stappen, and Gottfried Reznicek
- Subjects
General Pharmacology, Toxicology and Pharmaceutics - Published
- 2015
39. Brainatwork: Logging Cognitive Engagement and Tasks in the Workplace Using Electroencephalography
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Stefan Schneegass, Florian Alt, Mariam Hassib, Susanne Friedl, and Mohamed Khamis
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Experience sampling method ,medicine.diagnostic_test ,business.industry ,Computer science ,05 social sciences ,Applied psychology ,020207 software engineering ,Cognition ,Usability ,02 engineering and technology ,Electroencephalography ,computer.software_genre ,Random forest ,Informatik ,Task (computing) ,Videoconferencing ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,Human multitasking ,0501 psychology and cognitive sciences ,business ,computer ,050107 human factors - Abstract
Today's workplaces are dynamic and complex. Digital data sources such as email and video conferencing aim to support workers but also add to their burden of multitasking. Psychophysiological sensors such as Electroencephalography (EEG) can provide users with cues about their cognitive state. We introduce BrainAtWork, a workplace engagement and task logger which shows users their cognitive state while working on different tasks. In a lab study with eleven participants working on their own real-world tasks, we gathered 16 hours of EEG and PC logs which were labeled into three classes: central, peripheral and meta work. We evaluated the usability of BrainAtWork via questionnaires and interviews. We investigated the correlations between measured cognitive engagement from EEG and subjective responses from experience sampling probes. Using random forests classification, we show the feasibility of automatically labeling work tasks into work classes. We discuss how BrainAtWork can support workers on the long term through encouraging reflection and helping in task scheduling.
- Published
- 2017
40. Voxel-based analysis of grey and white matter degeneration in cervical spondylotic myelopathy
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Grabher, Patrick, Mohammadi, Siawoosh, Trachsler, Aaron, Friedl, Susanne, David, Gergely, Sutter, Reto, Weiskopf, Nikolaus, Thompson, Alan J., Curt, Armin, Freund, Patrick, University of Zurich, and Grabher, Patrick
- Subjects
Adult ,Male ,1000 Multidisciplinary ,Cervical Cord ,610 Medicine & health ,Middle Aged ,Magnetic Resonance Imaging ,White Matter ,Article ,Spinal Cord Diseases ,Patient Outcome Assessment ,Case-Control Studies ,Cervical Vertebrae ,Humans ,Female ,10046 Balgrist University Hospital, Swiss Spinal Cord Injury Center ,Spondylosis ,Gray Matter ,Aged - Abstract
In this prospective study, we made an unbiased voxel-based analysis to investigate above-stenosis spinal degeneration and its relation to impairment in patients with cervical spondylotic myelopathy (CSM). Twenty patients and 18 controls were assessed with high-resolution MRI protocols above the level of stenosis. Cross-sectional areas of grey matter (GM), white matter (WM), and posterior columns (PC) were measured to determine atrophy. Diffusion indices assessed tract-specific integrity of PC and lateral corticospinal tracts (CST). Regression analysis was used to reveal relationships between MRI measures and clinical impairment. Patients showed mainly sensory impairment. Atrophy was prominent within the cervical WM (13.9%, p = 0.004), GM (7.2%, p = 0.043), and PC (16.1%, p = 0.005). Fractional anisotropy (FA) was reduced in the PC (-11.98%, p = 0.006) and lateral CST (-12.96%, p = 0.014). In addition, radial (+28.47%, p = 0.014), axial (+14.72%, p = 0.005), and mean (+16.50%, p = 0.001) diffusivities were increased in the PC. Light-touch score was associated with atrophy (R(2) = 0.3559, p = 0.020) and FA (z score 3.74, p = 0.003) in the PC, as was functional independence and FA in the lateral CST (z score 3.68, p = 0.020). This study demonstrates voxel-based degeneration far above the stenosis at a level not directly affected by the compression and provides unbiased readouts of tract-specific changes that relate to impairment.
- Published
- 2016
41. Brainatwork
- Author
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Hassib, Mariam, primary, Khamis, Mohamed, additional, Friedl, Susanne, additional, Schneegass, Stefan, additional, and Alt, Florian, additional
- Published
- 2017
- Full Text
- View/download PDF
42. Voxel-based analysis of grey and white matter degeneration in cervical spondylotic myelopathy
- Author
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Grabher, Patrick, primary, Mohammadi, Siawoosh, additional, Trachsler, Aaron, additional, Friedl, Susanne, additional, David, Gergely, additional, Sutter, Reto, additional, Weiskopf, Nikolaus, additional, Thompson, Alan J., additional, Curt, Armin, additional, and Freund, Patrick, additional
- Published
- 2016
- Full Text
- View/download PDF
43. Antimicrobial activities of single aroma compounds
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Albena Stoyanova, Gerhard Buchbauer, Erich Schmidt, Zapryana Denkova, Margit Geissler, Jürgen Wanner, Leopold Jirovetz, Stefanie Bail, Susanne Mirjam Friedl, and Alexander Slavchev
- Subjects
Pharmacology ,food.ingredient ,biology ,Bacteria ,Chemistry ,Plant composition ,Plant Science ,General Medicine ,Microbial Sensitivity Tests ,biology.organism_classification ,Antimicrobial ,Perfume ,chemistry.chemical_compound ,food ,Complementary and alternative medicine ,Caryophyllene oxide ,Anti-Infective Agents ,Drug Discovery ,Candida albicans ,Organic chemistry ,Agar ,Food science ,Longifolene ,Aroma - Abstract
Commercially available aroma samples were evaluated for their olfactory quality by professional perfumers and tested for their antimicrobial activity. Agar diffusion and agar-dilution were used as test methods and a set of two Gram-positive ( Staphylococcus Aureus and Enterococcus faecalis) and four Gram-negative bacterial strains ( Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris G, Klebsiella pneumoniae and Salmonella abony) and a yeast, Candida albicans, were the test microorganisms. All the investigated compounds were active against Gram-positive bacteria, especially β-caryophyllene against Enterococcus faecalis (MIC 6 ppm), but only few substances showed activity towards Gram-negative bacteria, except for cinnamic acid, which was active against all (MIC 60 ppm) and Candida albicans, against which cinnamic acid and caryophyllene oxide showed high activity (MIC < 60 ppm).
- Published
- 2010
44. Quantification of 1,8-Cineole in Human Blood and Plasma and the Impact of Liner Choice in Head-Space Chromatography
- Author
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Friedl, Susanne, primary, Heuberger, Eva, additional, Oedendorfer, Katharina, additional, Kitzer, Simone, additional, Jaganjac, Lejla, additional, Stappen, Iris, additional, and Reznicek, Gottfried, additional
- Published
- 2015
- Full Text
- View/download PDF
45. Entwicklung eines interaktiven Trainingsprogrammes zur Behandlung dysfunktionaler Kommunikation von Paaren
- Author
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Friedl, Susanne
- Subjects
ddc:610 ,Paartherapie , Kommunikationstraining , Kommunikationsstörung , Dysfunktionale Kommunikation , couples therapy , Marital Enrichment ,610 Medizin - Abstract
Erstellung eines Kommunikationstrainingsprogammes für Paare zur Behandlung dysfunktionaler Kommunikation in der Partnerschaft als primär Prävention zur Vermeidung physischer und psychischer und sozialer Folgen von mangelnder oder ungenügender Paarzufriedenheit., Debelopement of an interactive - film based couples communication training program as a concept of health maintenance.
- Published
- 2009
46. Structure-activity relationships of sandalwood odorants: total synthesis and fragrance properties of cyclopropano-beta-santalol
- Author
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Susanne Mirjam Friedl, Iris Stappen, Claudia Pammer, Joris Höfinghoff, Peter Wolschann, and Gerhard Buchbauer
- Subjects
Models, Molecular ,Magnetic Resonance Spectroscopy ,Double bond ,Stereochemistry ,β-Santalol ,Ring (chemistry) ,Chemical synthesis ,Mass Spectrometry ,Cyclopropane ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,Organic chemistry ,Pharmacology ,Sandalwood ,chemistry.chemical_classification ,Polycyclic Sesquiterpenes ,biology ,Organic Chemistry ,Total synthesis ,General Medicine ,biology.organism_classification ,chemistry ,Odor ,Santalum ,Odorants ,Sesquiterpenes - Abstract
The synthesis and odor properties of cyclopropano-beta-santalol, a new santalol analogue, are described. The exocyclic double bond of the original molecule, beta-santalol, is replaced by a cyclopropane ring. Despite the analogies in the binding properties between the double bond and cyclopropane this change in the bulky hydrophobic part of the molecule leads to the complete loss of the characteristic sandalwood odor: in an olfactory evaluation the (Z)-product appears spicy and sweet, the (E)-isomer woody, but neither of them exhibits the typical sandalwood character.
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- 2007
47. Structure–activity relationships of sandalwood odorants: Total synthesis and fragrance properties of cyclopropano-β-santalol
- Author
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Stappen, Iris, Höfinghoff, Joris, Friedl, Susanne, Pammer, Claudia, Wolschann, Peter, and Buchbauer, Gerhard
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- 2008
- Full Text
- View/download PDF
48. Comparison of Liquid-Liquid Partition, HS-SPME and Static HS GC/MS Analysis for the Quantification of (–)-Linalool in Human Whole Blood Samples
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Friedl, Susanne Mirjam, primary, Oedendorfer, Katharina, additional, Kitzer, Simone, additional, Reznicek, Gottfried, additional, Sladek, Guenther, additional, and Heuberger, Eva, additional
- Published
- 2010
- Full Text
- View/download PDF
49. Antimicrobial Activities of Single Aroma Compounds
- Author
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Schmidt, Erich, primary, Bail, Stefanie, additional, Friedl, Susanne Mirjam, additional, Jirovetz, Leopold, additional, Buchbauer, Gerhard, additional, Wanner, Jürgen, additional, Denkova, Zapryana, additional, Slavchev, Alexander, additional, Stoyanova, Albena, additional, and Geissler, Margit, additional
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- 2010
- Full Text
- View/download PDF
50. Comparison of Liquid-Liquid Partition, HS-SPME and Static HS GC/MS Analysis for the Quantification of (–)-Linalool in Human Whole Blood Samples
- Author
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Katharina Oedendorfer, Guenther Sladek, Gottfried Reznicek, Eva Heuberger, Susanne Mirjam Friedl, and Simone Kitzer
- Subjects
Pharmacology ,Detection limit ,Chromatography ,Plant composition ,Analytical chemistry ,Plant Science ,General Medicine ,chemistry.chemical_compound ,Complementary and alternative medicine ,Linalool ,chemistry ,Liquid liquid partition ,Drug Discovery ,Solid Phase Micro Extraction ,Gas chromatography–mass spectrometry ,Whole blood - Abstract
The aim of this investigation was to develop a fast and convenient method for the determination of (-)-linalool in human whole blood to facilitate pharmacokinetic studies. Analytical protocols were elaborated for three different GC/MS sampling techniques, i.e., static headspace (s-HS), headspace solid phase micro extraction (HS-SPME), and liquid-liquid partition. In principle, all tested methods were feasible, but s-HS had the greatest benefit because of the easy handling of the blood samples and its short analysis time. For s-HS two different incubation temperatures were tested (40 degrees C and 60 degrees C). The limit of detection was slightly lower when samples were incubated at 60 degrees C, but the same quantitative results were achieved using alpha-terpineol as internal standard. An accurate and sensitive method for the quantification of (-)-linalool in blood samples after either inhalation or percutaneous application, as well as pharmacokinetic data are presented.
- Published
- 2010
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