Zürich, Switzerland
Zürich, Switzerland

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Schutz A.K.,ETH Zurich | Soragni A.,ETH Zurich | Hornemann S.,Universitats Spital Zurich | Aguzzi A.,Universitats Spital Zurich | And 3 more authors.
Angewandte Chemie - International Edition | Year: 2011

The analytical "gold standard" for amyloid characterization and diagnostics, Congo red, was studied in complex with an amyloid (see picture). Based on details of the binding mode, a point mutation of the amyloid was prepared which has the same three-dimensional structure as the wild-type protein but is not congophilic. This surprising specificity may aid in the design of selective anti-amyloidogenic drugs. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Guizouarn H.,French National Center for Scientific Research | Borgese F.,French National Center for Scientific Research | Gabillat N.,French National Center for Scientific Research | Harrison P.,University College London | And 4 more authors.
British Journal of Haematology | Year: 2011

The hereditary stomatocytoses are a group of dominantly inherited conditions in which the osmotic stability of the red cell is compromised by abnormally high cation permeability. This report demonstrates the very marked similarities between the cryohydrocytosis form of hereditary stomatocytosis and the common tropical condition south-east Asian ovalocytosis (SAO). We report two patients, one showing a novel cryohydrocytosis variant (Ser762Arg in SLC4A1) and a case of SAO. Both cases showed a mild haemolytic state with some stomatocytes on the blood film, abnormal intracellular sodium and potassium levels which were made markedly abnormal by storage of blood at 0°C, increased cation 'leak' fluxes at 37°C and increased Na+K+ pump activity. In both cases, the anion exchange function of the mutant band 3 was destroyed. Extensive electrophysiological studies comparing the cation leak and conductance in Xenopus laevis oocytes expressing the two mutant genes showed identical patterns of abnormality. These data are consistent with the cryohydrocytosis form of hereditary stomatocytosis and we conclude that the cation leak in SAO is indistinguishable from that in cryohydrocytosis, and that SAO should be considered to be an example of hereditary stomatocytosis. © 2011 Blackwell Publishing Ltd.

Mueller-Pfeiffer C.,Universitats Spital Zurich | Mueller-Pfeiffer C.,Massachusetts General Hospital
Schweizer Archiv fur Neurologie und Psychiatrie | Year: 2016

The most frequent traumatic experiences in Switzerland are accidents and violent acts with a lifetime prevalence of 5 and 2%, respectively. Approximately 15% of survivors develop a posttraumatic stress disorder (PTSD) in the aftermath of the traumatic event. PTSD is often accompanied with functional impairment. Consequently, PTSD plays a major role in insurance medicine. Forensic assessments often induce substantial stress in PTSD clients because the forensic setting may trigger traumatic feelings of fear and helplessness. Reliability of PTSD diagnosis and working capacity among evaluators are often insufficient. Here, we provide strategies for establishing a safe forensic relationship with traumatised clients. We propose a systematic approach to evaluating psychopathology, functional impairment and working capacity. We also address potential novel procedures such as a psychophysiological diagnostic laboratory test and limitations that need to be overcome in order to improve reliability and validity in forensic PTSD assessment.

Karbach J.,II. Medizinische Klinik | Neumann A.,II. Medizinische Klinik | Atmaca A.,II. Medizinische Klinik | Wahle C.,II. Medizinische Klinik | And 7 more authors.
Clinical Cancer Research | Year: 2011

Purpose: NY-ESO-1, one of the most immunogenic tumor antigens, is expressed in 15% to 25% of metastatic prostate cancers. The immunological and clinical effects of vaccination with recombinant NY-ESO-1 protein combined with CpG as adjuvant were evaluated. Experimental Design: In a phase I clinical study, patients with advanced prostate cancer were vaccinated with recombinant NY-ESO-1 protein (100 mg) mixed with CpG 7909 (2.5 mg) every 3 weeks intradermally for 4 doses. Objectives of the study were the safety of the vaccine and changes of specific humoral and cellular immunological responses to NY-ESO-1 in relation to detectable NY-ESO-1 expression in the individual tumor. Results: All 12 baseline sero-negative patients developed high-titer NY-ESO-1 antibody responses. B-cell epitope mapping identified NY-ESO-1 p91-110 to be recognized most frequently by vaccine-induced antibodies. Two patients developed significant antibody titers against the adjuvant CpG. NY-ESO-1-specific CD4+ and/or CD8+ T-cell responses were induced in 9 patients (69%). Five of these 9 patients did not express NY-ESO-1 in the autologous tumor. Postvaccine CD8+ T-cell clones recognized and lyzed HLA-matched tumor cell lines in an antigen-specific manner. Conclusion: Our data provide clear evidence for the capacity of NY-ESO-1 protein/CpG vaccine to induce integrated antigen-specific immune responses in vivo and to efficiently prime CD8+T-cell responses in NY-ESO-1 antigen-negative patients. Our results may also support further clinical vaccination protocols with NY-ESO-1 protein not only focused on the treatment of existing cancer, but also to prevent further development of NY-ESO-1 positive cancers in vivo. ©2010 AACR.

Aneurysms and dissections of the thoracic and abdominal aorta are the most common diseases of the aortic tree and are associated with a high morbidity and mortality caused by bleeding in case of rupture or malperfusion of vital organs in case of dissection. The knowledge of epidemiology, pathophysiology and clinical presentation allows the most appropriate diagnostic evaluation in both acute and chronic situations. Ultrasound is the ideal and most cost-effective imaging modality for screening and follow-up investigations of abdominal aortic aneurysms. Contrast-enhanced computed tomography is the most appropriate imaging for aneurysm of the thoracic aorta or for acute events with rupture or dissection.

Chew Y.-L.,UCSI University | Wong H.-C.,Universitats Spital Zurich
Oriental Pharmacy and Experimental Medicine | Year: 2016

Gynostemma pentaphyllum is consumed as herbal tea by the Chinese. It has been extensively studied in the past 20 years and the major secondary metabolites, gypenosides (Gyp) are known to exhibit many medicinal properties such as anti-cancers, anti-inflammatory, antipyretic, anti-hyperlipidemic, and anti-diabetic. This review summarizes the effect of Gyp towards various cancer cells, and reports the five apoptotic pathways taken by Gyp in inhibiting the cancer cell growth and development, namely (1) blocking of cancer cell initiation, (2) apoptosis via Ca2+ overload, (3) causing mitochondrial membrane depolarization via caspase dependent and independent pathways, (4) inhibition of DNA repair genes by downregulation and (5) anti-metastatic effect by downregulating the synthesis of numerous tumor-associated metastatic-related proteins. Both in vitro and in vivo studies of Gyp showed that it could inhibit cancer cell growth and development. These results showed that Gyp has a great potential to be used as herbal remedy and an alternative treatment for cancer. © 2016, Institute of Korean Medicine, Kyung Hee University and Springer Science+Business Media Dordrecht.

Goede J.S.,Universitats Spital Zurich
Therapeutische Umschau | Year: 2013

Asplenia is found in a very heterogeneous group of patients with a wide range of age and comorbidities. These patients have an increased risk of overwhelming post-splenectomy infections (OPSI) even several decades after splenectomy. The mortality rate associated with OPSI is 30-60 %, which is why the immunisation against encapsulated bacteria is mandatory. In addition these patients show an increased risk of thrombosis of the portal venous system. In the present article all the necessary, during daily practice often neglected preventsive measures and behavioural rules are discussed. © 2013 Verlag Hans Huber, Hogrefe AG, Bern.

Haslinger C.,Universitats Spital Zurich | Gonser M.,Klinik fur Geburtshilfe und Pranatalmedizin
Gynakologe | Year: 2015

Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disease. It occurs in the second half of pregnancy and is characterized by sometimes intensive, nocturnally increased maternal pruritus and raised maternal serum bile acid levels. The ICP has a good prognosis for the mother with usually rapid recovery after delivery but is associated with adverse fetal outcomes, such as preterm delivery, intrapartum fetal distress, meconium contamination of the amniotic fluid and stillbirth, particularly near term. Ursodeoxycholic acid (UDCA) is considered to be the first-line treatment for ICP and was shown to reduce maternal pruritus and to lower maternal serum bile acid levels. Stillbirth due to ICP is a consequence of acute anoxia and not due to chronic uteroplacental insufficiency. As a consequence the usual methods of fetal monitoring, such as ultrasound or cardiotocography (CTG), cannot be used to predict an adverse perinatal outcome. For this reason, early induction of labor after 37 weeks of gestation, also depending on serum bile acid levels, is recommended by many authors. © 2015, Springer-Verlag Berlin Heidelberg.

Straumann D.,Universitats Spital Zurich
Schweizer Archiv fur Neurologie und Psychiatrie | Year: 2011

The successful road to neuro-otology starts with an appreciation of phenomenology, in particular eye movements. Some physiological facts and "laws"concerning the vestibulo-ocular reflex (VOR) constitute the basis for accurate neuro-otological diagnosis. These include the frequency-dependence of the VOR, the concept of vestibular resting rate, the push-pull configuration of the semicircular canals, Ewald's second law, Alexander's law, and the inherent imbalance of vertical eye position. Only when one is able to distinguish normal from disordered ocular motor behaviour, and understands the underlying physiological mechanisms, is it possible to identify the affected neuro anatomical structures and establish accurate diagnoses.

Bertalanffy H.,Universitats Spital Zurich | Tissira N.,Universitats Spital Zurich | Krayenbuhl N.,Universitats Spital Zurich | Bozinov O.,Universitats Spital Zurich | Sarnthein J.,Universitats Spital Zurich
Neurosurgery | Year: 2011

BACKGROUND: Surgical exposure of intrinsic brainstem lesions through the floor of the 4th ventricle requires precise identification of facial nerve (CN VII) fibers to avoid damage. OBJECTIVE: To assess the shape, size, and variability of the area where the facial nerve can be stimulated electrophysiologically on the surface of the rhomboid fossa. METHODS: Over a period of 18 months, 20 patients were operated on for various brainstem and/or cerebellar lesions. Facial nerve fibers were stimulated to yield compound muscle action potentials (CMAP) in the target muscles. Using the sites of CMAP yield, a detailed functional map of the rhomboid fossa was constructed for each patient. RESULTS: Lesions resected included 14 gliomas, 5 cavernomas, and 1 epidermoid cyst. Of 40 response areas mapped, 19 reached the median sulcus. The distance from the obex to the caudal border of the response area ranged from 8 to 27 mm (median, 17 mm). The rostrocaudal length of the response area ranged from 2 to 15 mm (median, 5 mm). CONCLUSION: Facial nerve response areas showed large variability in size and position, even in patients with significant distance between the facial colliculus and underlying pathological lesion. Lesions located close to the facial colliculus markedly distorted the response area. This is the first documentation of variability in the CN VII response area in the rhomboid fossa. Knowledge of this remarkable variability may facilitate the assessment of safe entry zones to the brainstem and may contribute to improved outcome following neurosurgical interventions within this sensitive area of the brain. Copyright © 2011 by the Congress of Neurological Surgeons.

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