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1.
Testing association of rare genetic variants with resistance to three common antiseizure medications
Stefan Wolking Claudia Moreau Anne T. Nies Elke Schaeffeler Mark McCormack Pauls Auce Andreja Avbersek Felicitas Becker Martin Krenn Rikke S. Møller Marina Nikanorova Yvonne G. Weber Sarah Weckhuysen Gianpiero L. Cavalleri Norman Delanty Chantal Depondt Michael R. Johnson Bobby P.C. Koeleman Wolfram S. Kunz Anthony G. Marson Josemir W. Sander Graeme J. Sills Pasquale Striano Federico Zara Fritz Zimprich Matthias Schwab Roland Krause Sanjay M. Sisodiya Patrick Cossette Simon L. Girard Holger Lerche EpiPGX Consortium 《Epilepsia》2020,61(4):657-666
2.
Claudia Kunz Sonja Schuldt-Lieb Henning Gieseler 《Journal of pharmaceutical sciences》2018,107(3):887-896
The use of cosolvent systems has been demonstrated to shorten lengthy freeze-drying processes and improve the solubility and stability of certain active pharmaceutical ingredients. The goal of the present study was to evaluate the suitability of 2 thermal characterization techniques, differential scanning calorimetry and freeze-dry microscopy, and to identify an optimal cosolvent system. Binary mixtures of a cosolvent (tert-butanol, dimethyl sulfoxide, 1,4-dioxane, acetone, or ethanol) and water were investigated. Ternary mixtures of frequently used excipients (50 mg/g mannitol, sucrose, glycine, or polyvinylpyrrolidone [PVP]) and a solvent-water system were then analyzed for their thermal properties. PVP presented a particularly high glass transition temperature (Tg′) in 70% tert-butanol at ?17.9°C. Large needle-shaped crystals that have been shown to be associated with improved processability were observed with mannitol and PVP in 40% 1,4-dioxane. A heterogeneous sublimation rate of the solvent and water whose impact on product stability remained unclear was observed with PVP in 40% 1,4-dioxane. Freeze-dry microscopy analysis demonstrated a possible extension of the process time for PVP in 99% dimethyl sulfoxide due to a slowly moving sublimation front. Conceivable negative consequences and the need for special treatment for low-melting cosolvents, such as ethanol and acetone, were predicted and discussed. 相似文献
3.
Controlling residual solvent levels is a major concern in pharmaceutical freeze-drying from co-solvent systems. This review provides an overview of the factors influencing this process and estimates their potential to reduce residual solvents in freeze-dried products. Decreased solvent contents are potentially correlated with the lower solid content, complete excipient crystallization, higher water solubility, and smaller molecular sizes of the solvent. Although no general rule can be derived for the selection of appropriate freezing conditions, the freezing stage appears to play a major role in subsequent volatile retention. In contrast, diverse secondary drying conditions do not appear to impact the amount of solvent retained in lyophilisates, and modification of this stage is thus not assumed to be expedient. Co-solvents are strongly entrapped in an amorphous product matrix as soon as the local moisture content decreases below a certain level. Thus, the moisture content in the dried product layer adjacent to the sublimation interface might be a key factor. Therefore, extension of the high moisture content period during the primary drying phase as well as a postlyophilization humidification of the dried products are presumably promising approaches to promote solvent release. 相似文献
4.
Dr. Dr. C. S. Leiggener Ch. Kunz A. Lohri K. Fridrich K. Honigmann 《Oral and maxillofacial surgery》2005,9(1):48-52
Despite the introduction of highly active antiretroviral therapy (HAART), diffuse large B-cell lymphoma (DLBCL) remains a common malignancy in human immunodeficiency virus (HIV)-infected patients, especially the plasmablastic variant. About 50% of lymphomas in HIV patients are extranodal and half of them occur in the head and neck area. The main oral symptoms are pain, swelling, numbness and tooth mobility. We report the case of a 52-year-old patient with a known HIV infection and fracture of the angular region of the mandible. The fracture did not unite following open reduction and osteosynthesis. A biopsy performed at the time of revision revealed the diagnosis of a primary lymphoma in the mandible. After chemotherapy had induced complete remission of the lymphoma and autogenous iliac crest bone grafting had been performed the fracture united. Primary lymphoma in the mandible is a disease that presents with a nonspecific radiological appearance which may mimic osteomyelitis or periodontal pathology. A rapid and accurate diagnosis is critical for the appropriate treatment. In our experience HIV-positive patients with mandibular fracture should be treated according to the guidelines established for HIV-negative patients. However, risky compromises such as intraoral approach or hazardous fracture fixation should be avoided. 相似文献
5.
Jaquiéry C Aeppli C Cornelius P Palmowsky A Kunz C Hammer B 《International journal of oral and maxillofacial surgery》2007,36(3):193-199
Between January 1996 and December 2001, 72 out of 354 patients were included in a retrospective study analysing the outcome of repaired orbital wall defects. Selection was dependent on the availability of pre and postoperative CT scans and on ophthalmologic examination. In particular, orthoptical assessment was performed up to 1 year after operation. In 72 patients, 83 orbital wall defects were analysed and allocated to one of five categories. Accuracy and type of reconstruction were assessed in unilateral orbital wall defects (n=61) and compared with functional outcome. Reconstruction was performed by using PDS membrane (39%), calvarian bone (13%), titanium mesh (7%) or a combination of these materials (37%). Postoperatively, 91% of the patients had normal vision without double images within 20 degrees at every gaze. Accuracy of reconstruction correlated with severity of orbital injury and functional outcome. Functional outcome between category II and III fractures showed no significant difference. The medial margin of the lateral infraorbital fissure being preserved (category II fracture) facilitates reconstruction technically. Accuracy of orbital reconstruction is one important factor to obtain best functional outcome, but other determinants like displacement and/or atrophy of intramuscular cone fat should be considered. 相似文献
6.
Christoph Kunz Lorenz Brauchli Torsten Moehle Berton Rahn Beat Hammer 《Journal of oral and maxillofacial surgery》2003,61(3):364-368
PURPOSE: This theoretical pilot study investigated the geometric changes necessary to normalize the mandibular shape in hemifacial microsomia. Using the mandibular deformity of a 13-year-old patient affected by hemifacial microsomia as an example, we addressed 2 main issues. First, the number of segments needed for adequate reshaping of the deformed mandible is evaluated. Second, the geometry of the intersegmental gaps resulting from reposition of the segments is correlated with established parameters of distraction osteogenesis to theoretically predict the practicability of correction using multifocal distraction osteogenesis. MATERIALS AND METHODS: Virtual surgery was performed on a solid mandible model created from computed tomography (CT) data from a patient with hemifacial microsomia type IIB. In the first step, ideal mandibular reshaping was achieved according to anthropometric standard measurements using 7 osteotomies. By scanning and superimposition of the virtual models and variation of distraction sites and numbers, we assessed the minimal number of osteotomies necessary for optimal correction of the deformity. Geometrical evaluation of the regeneration and assessment of the possibilities of continuous curved distraction were also performed. RESULTS: Three osteotomies were shown to be sufficient for complete mandibular reshaping. Using accepted parameters for distraction osteogenesis, the geometry of the regenerate allows for continuous curved distraction. However, simultaneous movements at several distraction sites result in interfering vector forces, making coordination of multifocal distraction difficult. CONCLUSION: Theoretical assessment of a severe mandibular hypoplasia in hemifacial microsomia revealed the 3-dimensional (3D) complexity of the deformity for corrective procedures, especially distraction osteogenesis. Despite precise planning and transfer of the plan to the patient, multifocal 3D distraction may result in deviations from the planned result. Manipulation of the fresh regeneration may be necessary to correct inaccuracies. 相似文献
7.
In this meta-analysis, we evaluated the effectiveness of dance movement therapy1 (DMT) and the therapeutic use of dance for the treatment of health-related psychological problems. Research in the field of DMT is growing, and 17 years have passed since the last and only general meta-analysis on DMT (Ritter & Low, 1996) was conducted. This study examines the current state of knowledge regarding the effectiveness of DMT and dance from 23 primary trials (N = 1078) on the variables of quality of life, body image, well-being, and clinical outcomes, with sub-analysis of depression, anxiety, and interpersonal competence. Results suggest that DMT and dance are effective for increasing quality of life and decreasing clinical symptoms such as depression and anxiety. Positive effects were also found on the increase of subjective well-being, positive mood, affect, and body image. Effects for interpersonal competence were encouraging, but due to the heterogenity of the data remained inconclusive. Methodological shortcomings of many primary studies limit these encouraging results and, therefore, further investigations to strengthen and expand upon evidence-based research in DMT are necessary. Implications of the findings for health care, research, and practice are discussed. 相似文献
8.
Pain catastrophizing has recently been suggested to have a social function based on a positive association observed with facial responsiveness to noxious stimulation. However, this assumption is based on studies applying nociceptive stimuli of fixed intensity, such that high catastrophizers not only displayed increased pain behavior but also rated the stimulation as being more painful. The aim of this study was to investigate the relation between catastrophizing and facial responsiveness while controlling for individual differences in pain sensitivity. The facial expression of pain was investigated in 44 young and pain-free individuals in response to painful and non-painful phasic heat stimuli. Painful temperatures were tailored to the individual sensitivity to produce moderate pain. Facial responses were videotaped and objectively examined using the Facial Action Coding System. We also assessed skin conductance activity as an autonomic indicator of pain-related responses. Catastrophizing was assessed using the Pain Catastrophizing Scale (PCS). In accordance with previous findings, subjects scoring higher on pain catastrophizing required lower thermal intensities to induce a moderately painful sensation (r=-0.40, p=0.007). However, catastrophizing did not correlate with facial responsiveness to perceptually controlled painful stimulation (r=-0.02, p=0.88). Moreover, correlation analyses revealed no significant associations between catastrophizing and skin conductance responses. The present findings provide further support for the impact of pain catastophizing on pain sensitivity. However, our finding of no relation between catastrophizing and facial responsiveness when participants are experiencing comparable psychophysical pain intensities, challenges previous assumptions that high catastrophizers display amplified pain behavior; at least in young and pain-free individuals. 相似文献
9.
Background
The tasks involved in reconstructing the urethra after failed hypospadias repair range from correction of a trivial meatal stenosis to reconstruction of the entire anterior urethra.Objectives
To describe pathological findings in the urethra after failed hypospadias repair and the respective surgical methods used for their correction.Materials and methods
The various pathological findings after unsuccessful hypospadias surgery are classified according to their location and complexity.Results
The general rules of reconstruction that should be applied in each particular situation are described.Conclusions
Successful reconstruction of the urethra in patients with failed hypospadias surgery requires experience and good knowledge of the anatomy of the normal and hypospadic urethra and penis. Mastery of plastic surgical techniques and profound knowledge of the various surgical methods of hypospadias surgery are essential.10.
Pierre Kunz Paul Mick Sascha Gross Gerhard Schmidmaier Felix Zeifang Marc-André Weber Christian Fischer 《Journal of orthopaedic research》2020,38(5):1150-1158
Supraspinatus (SSP) tendon tears represent a common indication for shoulder surgery. Yet, prediction of postoperative function and tendon retear remains challenging and primarily relies on morphologic magnetic resonance imaging (MRI)-based parameters, supported by patients' demographic data like age, gender, and comorbidities. Considering continuously high retear rates, especially in patients with larger tears and negative prognostic factors, improved outcome prediction could be of high clinical value. Contrast-enhanced ultrasound (CEUS) enables an assessment of dynamic perfusion of the SSP muscle. As a potential surrogate for muscle vitality, CEUS might reflect functional properties of the SSP and support improved outcome prediction after tendon repair. Fifty patients with isolated SSP tendon tears were prospectively enrolled. Preoperatively, SSP muscle perfusion was quantified by CEUS and conventional morphologic parameters like tear size, fatty infiltration, and tendon retraction were assessed by MRI. At six months follow-up, shoulder function, tendon integrity, and muscle perfusion were reassessed. The predictive value of preoperative CEUS for postoperative shoulder function and tendon integrity was evaluated. 35 patients entered the statistical analysis. Preoperative CEUS-based assessment of SSP perfusion significantly correlated with early postoperative shoulder function (Constant, r = 0.48, p < 0.018) and tendon retear (r = 0.67, p < 0.001). CEUS-based subgroup analysis identified patients with exceptionally high, respectively low risk for tendon retear. CEUS-based assessment of the SSP seemed to predict early shoulder function and tendon retear after SSP repair and allowed to identify patient subgroups with exceptionally high or low risk for tendon retear. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:1150-1158, 2020 相似文献