Kliniken der Stadt Cologne
Kliniken der Stadt Cologne
Tischfield M.A.,Childrens Hospital Boston |
Tischfield M.A.,Harvard University |
Baris H.N.,Childrens Hospital Boston |
Wu C.,Childrens Hospital Boston |
And 63 more authors.
Cell | Year: 2010
We report that eight heterozygous missense mutations in TUBB3, encoding the neuron-specific β-tubulin isotype III, result in a spectrum of human nervous system disorders that we now call the TUBB3 syndromes. Each mutation causes the ocular motility disorder CFEOM3, whereas some also result in intellectual and behavioral impairments, facial paralysis, and/or later-onset axonal sensorimotor polyneuropathy. Neuroimaging reveals a spectrum of abnormalities including hypoplasia of oculomotor nerves and dysgenesis of the corpus callosum, anterior commissure, and corticospinal tracts. A knock-in disease mouse model reveals axon guidance defects without evidence of cortical cell migration abnormalities. We show that the disease-associated mutations can impair tubulin heterodimer formation in vitro, although folded mutant heterodimers can still polymerize into microtubules. Modeling each mutation in yeast tubulin demonstrates that all alter dynamic instability whereas a subset disrupts the interaction of microtubules with kinesin motors. These findings demonstrate that normal TUBB3 is required for axon guidance and maintenance in mammals. © 2010 Elsevier Inc. All rights reserved.
PubMed | University of Cologne, Universitatsklinikum Bonn, Gemeinschaftspraxis, Universitatsmedizin Mainz and 8 more.
Type: Journal Article | Journal: Laryngo- rhino- otologie | Year: 2014
A new and interdisciplinary S2k AWMF guideline for the treatment of obstructive sialadenitis has been published. There have been several technical achievements, for instance in the field of ultrasonography, via sialendoscopy, or by MR-sialography, that have increased the possibilities for diagnosis and treatment of patients with obstructive sialadenitis. In the past, the treatment of choice in case of unsuccessful medical treatment was a complete extirpation of the affected salivary gland. Nowadays, using a variety of modern treatment options (like sialendoscopy, or extracorporeal shock-waves lithotripsy sometimes combined with salivary duct incision), it is possible in most patients, especially in cases of sialolithiasis, to preserve the affected gland. A functional recovery after gland-sparing surgery is described but more data is needed to finally evaluate the long-time results. The new guideline describes all relevant steps to diagnose an obstructive sialadenitis and values all diagnostic tools critically. Finally, all recommendable therapy options are described and valued, too.
PubMed | Tumorgenetik Bonn Kooperation fur Tumordiagnostik, Lilly Deutschland, Airway Research Center North, Lilly France and 10 more.
Type: Clinical Trial, Phase II | Journal: Lung cancer (Amsterdam, Netherlands) | Year: 2016
We investigated the feasibility of cisplatin or carboplatin combined with pemetrexed as adjuvant treatment in patients with completely resected Stage IB/II Non-Small-Cell Lung Cancer (NSCLC).Patients in this multicenter, open-label, parallel-group, non-comparative Phase 2 study were randomized (1:1) to pemetrexed (500 mg/m(2)) with either cisplatin (75 mg/m(2)) or carboplatin (AUC5) for 4 cycles of 21 days. The primary endpoint was treatment feasibility (defined as 4 cycles completed with no cycle delay >42 days and 2 dose reductions, with a median relative dose intensity (RDI) 95% [overall]; and no Grade 3 toxicities at the follow-up visit 30 days after last drug administration). Secondary objectives included overall survival (OS) and safety.We randomized 122 patients and treated 118. 71.9% (46/64) of patients in pemetrexed+cisplatin and 88.9% (48/54) in pemetrexed+carboplatin completed 4 cycles (median RDI >97% for all compounds). Neither treatment met the pre-defined feasibility level >60% of patients: 59.4% (95% confidence interval [CI]: 46.4;71.5) pemetrexed+cisplatin; 50.0% (95%CI: 36.1;63.9) in pemetrexed+carboplatin. In a post-hoc analysis considering only safety, both regimens were feasible with 81.3% (95%CI: 69.5;89.9) in pemetrexed+cisplatin and 90.7% (95%CI: 79.7;96.9) in pemetrexed+carboplatin. OS rates for both groups were 82-83% after 3 years and 80-83% after 5 years. Treatment-related Grade 3 adverse events (mostly hematological) were experienced by approximately 30% of patients in each group.Although the study did not meet the primary objective, both treatment groups demonstrated good safety-related feasibility and tolerability as adjuvant treatment in patients with completely resected Stage IB/II NSCLC.
Schrage N.,Aachener Centrum fur Technologietransfer in der Ophthalmologie |
Cordes A.K.,Kliniken der Stadt Cologne |
Storsberg J.,Fraunhofer Institute for Applied Polymer Research |
Sel S.,Universitatsaugenklinik Halle Saale |
And 6 more authors.
Ophthalmologe | Year: 2014
Background: Clinical application of a keratoprosthesis (KPRO) is still a challenging task. Recent developments reflect the concepts of nut and bolt, intrastromal implantation or an osteoodontokeratoprosthesis (OOKP). A new concept of a textile KPRO has been evaluated in a limited human study with considerable difficulties which after termination of the study and considerable improvements was restarted using animal experiments. Materials: The ACTO TexKPRO is made from polyvinylidene difluoride (PVDF) fibers and transparent silicone. The first and second developmental stages differed in density and size of fibers and furthermore in surface modifications of the fibers and optics which were improved for the second prototype. Methods: Implantation of the prosthesis was performed in four patients with corneal blindness and in two cases retinal disease which required surgery. In the later animal experiments surgery was performed on three rabbits. Surgery was performed by redressing the conjunctiva, opening of the eyeball with a central 6.5 mm trephination, removal of the lens and iris and implantation and suturing of the TexKPRO. If required a silicone oil endotamponade was placed. Results: All eyes were stable with the keratoprosthesis. The first prototype showed conjunctival recession on the textile haptics with highly susceptible endopthalmitis risk due to infection of the PVDF so that we decided to remove the prosthesis from all eyes after one case of severe endophthalmitis occurred. The longest time of placement was 40 months and the shortest time 6 months. All eyes were restored by keratoplasty. In animals with the new haptic we found better conjunctivalization and stable implantation of the KPRO. Discussion: The textile KPRO provides a stable implantation procedure and safe connection of fibers to the scleral wound bed. The optical and mechanical implantation is safe and stable. Surface epithelialization is improved with the new surface modifications and different PVDF fiber density but beforel new implantations are planned further conceptual changes will be introduced. © Springer-Verlag Berlin Heidelberg 2013.
Hugle U.,Kliniken der Stadt Cologne |
Muller-Gerbes D.,Kliniken der Stadt Cologne |
Schulte-Fischedick A.,Kliniken der Stadt Cologne |
Dormann A.,Kliniken der Stadt Cologne
Endoskopie Heute | Year: 2015
Long-term pH monitoring is an important element in diagnosing gastroesophageal reflux disease (GERD) and is considered the gold standard for determining acid exposure in the distal oesophagus. Problems with patient acceptance and compliance with the transnasal probe have encouraged further development of a catheter-free, telemetric measuring system, the BRAVO capsule, with an extended analysis time of 96Â hours. Unlike techniques described in the literature, the BRAVO capsule is placed in the distal oesophagus under endoscopic control. The level in the oesophagus (5 cm above the GE-Junction) is precisely defined beforehand by endoscopy, improving the diagnostic accuracy. The dislocation could be reduced. The Bravo system allows the patient to continue with normal daily activities, eat relatively normally and ensures virtually no interference with the respiratory passages. It offers a very high level of wearing comfort. © Georg Thieme Verlag KG.
Muller-Gerbes D.,Kliniken der Stadt Cologne |
Beeck A.,Kliniken der Stadt Cologne |
Dormann A.,Kliniken der Stadt Cologne
Endoskopie Heute | Year: 2013
Hemostasis with powder is a new surface-covering principle of endoscopic hemostasis without mucosa-invasion. EndoClotTM consists of particles of modified polysaccharides which are derived from starch. The AMP ® particles (Absorbable Modified Polymer) withdraw water from the blood forming a gel. Thereby an adhesive clot is formed on the source of the bleeding. Simultaneously, the concentration of coagulation factors is increased, accelerating the physiological coagulation. We could apply this method with 22 patients. In 21 of 22 patients, successful hemostasis was achieved, in 5 cases in addition to other methods, in 16 cases as mono-therapy. Both on diffuse tumor bleedings and on significant clotting disorders respectively anticoagulation the method was successful. There were no complications or side effects. EndoClotTM could become accepted as selective and additive mean of hemostasis in difficult bleeding-scenarios, possibly as bridging until clotting-stabilization has been reached. This should be investigated in further controlled studies.©Georg Thieme Verlag KGStuttgart New York.
Ilko D.,University of Würzburg |
Steiger C.,University of Würzburg |
Keller R.,Kliniken der Stadt Cologne |
Holzgrabe U.,University of Würzburg |
Meinel L.,University of Würzburg
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2016
Counterfeit drugs are a major threat to public health. Current efforts focus on serialization of the secondary packaging which do not allow to trace the individual unit. As a proof of concept, we intended to mark each tablet for its unambiguous recognition. Spiking monodisperse PEGs into tablet coating solutions at concentrations as low as 3 ppm was instrumental to "write" a code into each tablet film which was readily read upon isolation and LC-MS/MS analysis. Different qualities and amounts of monodisperse polyethylene glycols can be used for coding solid drug products. The approach is limited to cases in which PEGs are not present for formulation purposes as excipients, as coding against this background was unfeasible. © 2015 Elsevier B.V. All rights reserved.
Suarez E.T.,Kliniken der Stadt Cologne
Ophthalmologe | Year: 2012
Sequelae of facial palsy are often underdiagnosed. The ophthalmologist plays a pivotal role in the acute, subacute and chronic treatment of this condition. Goals are to provide corneal protection, restoration of facial asymmetry and facial movements and the treatment of crocodile tears. Botulinum toxin is the first line treatment for sequelae due to aberrant regeneration. The indications and techniques for treatment with botulinum toxin in patients with facial palsy are presented. © 2012 Springer-Verlag.
PubMed | Kliniken der Stadt Cologne
Type: Journal Article | Journal: Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft | Year: 2012
Sequelae of facial palsy are often underdiagnosed. The ophthalmologist plays a pivotal role in the acute, subacute and chronic treatment of this condition. Goals are to provide corneal protection, restoration of facial asymmetry and facial movements and the treatment of crocodile tears. Botulinum toxin is the first line treatment for sequelae due to aberrant regeneration. The indications and techniques for treatment with botulinum toxin in patients with facial palsy are presented.
PubMed | Kliniken der Stadt Cologne and University of Würzburg
Type: | Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V | Year: 2016
Counterfeit drugs are a major threat to public health. Current efforts focus on serialization of the secondary packaging which do not allow to trace the individual unit. As a proof of concept, we intended to mark each tablet for its unambiguous recognition. Spiking monodisperse PEGs into tablet coating solutions at concentrations as low as 3 ppm was instrumental to write a code into each tablet film which was readily read upon isolation and LC-MS/MS analysis. Different qualities and amounts of monodisperse polyethylene glycols can be used for coding solid drug products. The approach is limited to cases in which PEGs are not present for formulation purposes as excipients, as coding against this background was unfeasible.