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1.
J Cyst Fibros ; 22(3): 515-524, 2023 May.
Article in English | MEDLINE | ID: mdl-36567205

ABSTRACT

BACKGROUND: The majority of variants of unknown clinical significance (VUCS) in the CFTR gene are missense variants. While change on the CFTR protein structure or function is often suspected, impact on splicing may be neglected. Such undetected splicing default of variants may complicate the interpretation of genetic analyses and the use of an appropriate pharmacotherapy. METHODS: We selected 15 variants suspected to impact CFTR splicing after in silico predictions on 319 missense variants (214 VUCS), reported in the CFTR-France database. Six specialized laboratories assessed the impact of nucleotide substitutions on splicing (minigenes), mRNA expression levels (quantitative PCR), synthesis and maturation (western blot), cellular localization (immunofluorescence) and channel function (patch clamp) of the CFTR protein. We also studied maturation and function of the truncated protein, consecutive to in-frame aberrant splicing, on additional plasmid constructs. RESULTS: Six of the 15 variants had a major impact on CFTR splicing by in-frame (n = 3) or out-of-frame (n = 3) exon skipping. We reclassified variants into: splicing variants; variants causing a splicing defect and the impairment of CFTR folding and/or function related to the amino acid substitution; deleterious missense variants that impair CFTR folding and/or function; and variants with no consequence on the different processes tested. CONCLUSION: The 15 variants have been reclassified by our comprehensive approach of in vitro experiments that should be used to properly interpret very rare exonic variants of the CFTR gene. Targeted therapies may thus be adapted to the molecular defects regarding the results of laboratory experiments.


Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator , Cystic Fibrosis , Humans , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/drug therapy , Cystic Fibrosis/genetics , Exons , RNA Splicing/genetics , Mutation, Missense , Mutation
2.
Front Bioeng Biotechnol ; 9: 676894, 2021.
Article in English | MEDLINE | ID: mdl-34268296

ABSTRACT

Take-off is a critical phase of flight, and many birds jump to take to the air. Although the actuation of the hindlimb in terrestrial birds is not limited to the sagittal plane, and considerable non-sagittal plane motion has been observed during take-off jumps, how the spatial arrangement of hindlimb muscles in flying birds facilitates such jumps has received little attention. This study aims to ascertain the 3D hip muscle function in the magpie (Pica pica), a bird known to jump to take-off. A musculoskeletal model of the magpie hindlimb was developed using µCT scans (isotropic resolution of 18.2 µm) to derive bone surfaces, while the 3D muscle path definition was further informed by the literature. Function was robustly characterized by determining the 3D moment-generating capacity of 14 hip muscles over the functional joint range of motion during a take-off leap considering variations across the attachment areas and uncertainty in dynamic muscle geometry. Ratios of peak flexion-extension (FE) to internal-external rotation (IER) and abduction-adduction (ABD) moment-generating capacity were indicators of muscle function. Analyses of 972 variations of the 3D muscle paths showed that 11 of 14 muscles can act as either flexor or extensor, while all 14 muscles demonstrated the capacity to act as internal or external rotators of the hip with the mean ratios of peak FE to IER and ABD moment-generating capacity were 0.89 and 0.31, respectively. Moment-generating capacity in IER approaching levels in the FE moment-generating capacity determined here underline that the avian hip muscle function is not limited to the sagittal plane. Together with previous findings on the 3D nature of hindlimb kinematics, our results suggest that musculoskeletal models to develop a more detailed understanding of how birds orchestrate the use of muscles during a take-off jump cannot be restricted to the sagittal plane.

3.
Scand J Trauma Resusc Emerg Med ; 29(1): 39, 2021 Feb 25.
Article in English | MEDLINE | ID: mdl-33632277

ABSTRACT

BACKGROUND: The effect of mechanical CPR is diversely described in the literature. Different mechanical CPR devices are available. The corpuls cpr is a new generation of piston-driven devices and was launched in 2015. The COMPRESS-trial analyzes quality of chest compression and CPR-related injuries in cases of mechanical CPR by the corpuls cpr and manual CPR. METHODS: This article describes the design and study protocol of the COMPRESS-trial. This observational multi-center study includes all patients who suffered an out-of-hospital cardiac arrest (OHCA) where CPR is attempted in four German emergency medical systems (EMS) between January 2020 and December 2022. EMS treatment, in-hospital-treatment and outcome are anonymously reported to the German Resuscitation Registry (GRR). This information is linked with data from the defibrillator, the feedback system and the mechanical CPR device for a complete dataset. Primary endpoint is chest compression quality (complete release, compression rate, compression depth, chest compression fraction, CPR-related injuries). Secondary endpoint is survival (return of spontaneous circulation (ROSC), admission to hospital and survival to hospital discharge). The trial is sponsored by GS Elektromedizinische Geräte G. Stemple GmbH. DISCUSSION: This observational multi-center study will contribute to the evaluation of mechanical chest compression devices and to the efficacy and safety of the corpuls cpr. TRIAL REGISTRATION: DRKS, DRKS-ID DRKS00020819 . Registered 31 July 2020.


Subject(s)
Cardiopulmonary Resuscitation/instrumentation , Cardiopulmonary Resuscitation/methods , Out-of-Hospital Cardiac Arrest/therapy , Outcome Assessment, Health Care , Quality of Health Care , Adult , Emergency Medical Services , Female , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , Registries
4.
Radiologe ; 60(10): 927-933, 2020 Oct.
Article in German | MEDLINE | ID: mdl-32809036

ABSTRACT

CLINICAL/METHODOLOGICAL ISSUE: COVID-19 is a new viral disease that is associated with inflammatory pulmonary changes which can be detected in computed tomography (CT). So far postmortem CT (PMCT) has not been used as a screening instrument for the evaluation of deaths with and without autopsy. In this respect, its validity has to be proved in comparison to clinical-radiological experiences. STANDARD RADIOLOGICAL METHODS: Postmortem CT METHODICAL INNOVATIONS: So far, PMCT can be regarded as a methodological innovation that has not yet been sufficiently evaluated for pneumonia. PERFORMANCE: CT in clinical routine has a high sensitivity for pneumonia. However, to what extent postmortem artifacts are relevant to PMCT still has to be determined. ACHIEVEMENTS: There is still no standard procedure for the postmortem radiological diagnosis of COVID-19 disease. Despite postmortem artifacts, PMCT can provide valuable information about the presence of pneumonia with interstitial character, especially without autopsy. PRACTICAL RECOMMENDATIONS: PMCT is particularly useful in the assessment of suspected cases of COVID-19 pneumonia for morphological assessment in the context of monitoring deaths in the current pandemic situation.


Subject(s)
Autopsy , Coronavirus Infections , Pandemics , Pneumonia, Viral , Betacoronavirus , COVID-19 , SARS-CoV-2 , Tomography, X-Ray Computed
5.
Fungal Syst Evol ; 5: 187-196, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32467923

ABSTRACT

Our understanding of the systematics of red yeasts has greatly improved with the availability of sequence data and it is now clear that the majority of these fungi belong to three different classes of Pucciniomycotina (Basidiomycota): Agaricostilbomycetes, Cystobasidiomycetes, and Microbotryomycetes. Despite improvements in phylogenetic placement, the taxonomy of these fungi has long been in need of revision and still has not been entirely resolved, partly due to missing taxa. In the present study, we present data of culture-based environmental yeast isolation, revealing several undescribed species of Symmetrospora, which was recently introduced to accommodate six species previously placed in the asexual genera Sporobolomyces and Rhodotorula in the gracilis/marina clade of Cystobasidiomycetes. Based on molecular phylogenetic analyses of three rDNA loci, morphology, and biochemical studies, we formally describe the following new species: Symmetrospora clarorosea sp. nov. from leaf surfaces in Portugal and the USA; S. pseudomarina sp. nov. from leaf surfaces in Brazil, and the USA and decaying wood in the USA; and S. suhii sp. nov. from a beetle gut in the USA, leaf surfaces in Brazil and marine water in the Taiwan and Thailand. Finally, we propose a new combination for Sporobolomyces oryzicola based on our molecular phylogenetic data, Symmetrospora oryzicola comb. nov.

6.
J Biomech ; 84: 4-10, 2019 02 14.
Article in English | MEDLINE | ID: mdl-30661733

ABSTRACT

Accurate determination of joint axes is essential for understanding musculoskeletal function. Whilst numerous algorithms to compute such axes exist, the conditions under which each of the methods performs best remain largely unknown. Typically, algorithms are evaluated for specific conditions only limiting the external validity of conclusions regarding their performance. We derive exact mathematical relationships between three commonly used algorithms for computing joint axes from motion data: finite helical axes (FHA), instantaneous helical axes (IHA) and SARA (symmetrical axis of rotation approach), including relationships for an extension to the mean helical axes methods that facilitate determining joint centres and axes. Through the derivation of a sound mathematical framework to objectively compare the algorithms we demonstrate that the FHA and SARA approach are equivalent for the analysis of two time frames. Moreover, we show that the position of a helical axis derived from the IHA using positional data is affected by a systematic error perpendicular to the true axis direction, whereas the axis direction is identical to those computed with either the FHA or SARA approach (true direction). Finally, with an appropriate choice of weighting factors the mean FHA (MFHA) method is equivalent to the Symmetrical Centre of Rotation Estimation (SCoRE) algorithm for determination of a Centre of Rotation (CoR), and similarly, equivalent to the SARA algorithm for determination of an Axis of Rotation (AoR). The deep understanding of the equivalences between methods presented here enables readers to choose numerically efficient, robust methods for determining AoRs and CoRs with confidence.


Subject(s)
Algorithms , Computational Biology , Joints , Mechanical Phenomena , Biomechanical Phenomena , Humans , Joints/physiology , Movement , Range of Motion, Articular , Rotation
7.
J Vet Intern Med ; 32(1): 516-524, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29377356

ABSTRACT

BACKGROUND: The prevention of bovine respiratory disease complex (BRD) in beef cattle is important to maintaining health and productivity of calves in feeding operations. OBJECTIVE: Determine whether BRD bacterial and viral pathogens are susceptible to the lactoperoxidase/hydrogen peroxide/iodide (LPO/H2 O2 /I- ) system in vitro and to determine whether the oral administration of sodium iodide (NaI) could achieve sufficient concentrations of iodine (I) in the respiratory secretions of weaned beef calves to inactivate these pathogens in vivo. ANIMALS: Sixteen weaned, apparently healthy, commercial beef calves from the University of Missouri, College of Veterinary Medicine teaching herd. METHODS: In vitro viral and bacterial assays were performed to determine susceptibility to the LPO/H2 O2 /I- system at varying concentrations of NaI. Sixteen randomly selected, healthy crossbred beef weanlings were administered 70 mg/kg NaI, or water, orally in a blinded, placebo-controlled trial. Blood and nasal secretions were collected for 72 hours and analyzed for I- concentration. RESULTS: Bovine herpesvirus-1, parainfluenza-3, Mannheimia haemolytica and Bibersteinia trehalosi were all inactivated or inhibited in vitro by the LPO/H2 O2 /I- reaction. Oral administration of NaI caused a marked increase in nasal fluid I concentration with a Cmax  = 181 (1,420 µM I), T12 , a sufficient concentration to inactivate these pathogens in vitro. CONCLUSIONS AND CLINICAL IMPORTANCE: In vitro, the LPO/H2 O2 /I- system inactivates and inhibits common pathogens associated with BRD. The administration of oral NaI significantly increases the I concentration of nasal fluid indicating that this system might be useful in preventing bovine respiratory infections.


Subject(s)
Bovine Respiratory Disease Complex/prevention & control , Nasal Mucosa/chemistry , Sodium Iodide/pharmacology , Administration, Oral , Animals , Bovine Respiratory Disease Complex/microbiology , Bovine Respiratory Disease Complex/virology , Cattle , Herpesvirus 1, Bovine/drug effects , Hydrogen Peroxide/chemistry , Iodine/analysis , Lactoperoxidase/metabolism , Mannheimia haemolytica/drug effects , Nasal Mucosa/microbiology , Nasal Mucosa/virology , Parainfluenza Virus 3, Human/drug effects , Pasteurellaceae/drug effects , Sodium Iodide/administration & dosage , Sodium Iodide/analysis
8.
J Biomed Mater Res A ; 106(2): 419-427, 2018 02.
Article in English | MEDLINE | ID: mdl-28971567

ABSTRACT

Biomimetic surface modifications of titanium (Ti) implants using the Arg-Gly-Asp-sequence (RGD) are promising to accelerate bone healing in cases of medical implants. Therefore, we compared the impact of linear and cyclic RGD (l- and c-RGD) covalently coupled onto Ti surfaces on the osseous response in vitro and in vivo. In vitro, osteoblasts' behavior on different surfaces (unmodified, amino-silanized [APTES], l- and c-RGD) was analysed regarding adhesion (fluorescence microscopy), proliferation (resazurin stain) and differentiation (reverse transcription polymerase chain reaction on alkaline phosphatase and osteocalcin). In vivo, osteosynthesis screws (unmodified n = 8, l-RGD n = 8, c-RGD n = 8) were inserted into the proximal tibiae of 12 rabbits and evaluated for bone growth parameters (bone implant contact [%] and vertical bone apposition [VBA;%]) at 3 and 6 weeks. In vitro, c- as well as l-RGD surfaces stimulated osteoblasts' adherence, proliferation and differentiation in a similar manner, with only subtle evidence of superiority of the c-RGD modifications. In vivo, c-RGD-modifications led to a significantly increased VBA after 3 and 6 weeks. Thus, coating with c-RGD appears to play an important role influencing osteoblasts' behaviour in vitro but especially in vivo. These findings can be applied prospectively to implantable biomaterials with hypothetically improved survival and success rates. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 106A: 419-427, 2018.


Subject(s)
Bone and Bones/physiology , Peptides, Cyclic/pharmacology , Titanium/pharmacology , Amines/chemistry , Animals , Bone and Bones/drug effects , Cell Adhesion/drug effects , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Female , Humans , Osteoblasts/cytology , Osteoblasts/drug effects , Rabbits , Surface Properties
9.
Bone Joint J ; 99-B(12): 1584-1589, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29212680

ABSTRACT

AIMS: This study sought to establish the prevalence of the cross over sign (COS) and posterior wall sign (PWS) in relation to the anterior pelvic plane (APP) in an asymptomatic population through reliable and accurate 3D-CT based assessment. MATERIALS AND METHODS: Data from pelvic CT scans of 100 asymptomatic subjects (200 hips) undertaken for conditions unrelated to disorders of the hip were available for analysis in this study. A previously established 3D analysis method was applied to assess the prevalence of the COS and PWS in relation to the APP. RESULTS: Of the 200 included hips, 24% (48) presented a positive COS and 5.5% (11) presented a positive PWS. A combination of COS and PWS was observed in 1% (two) of all hips (1%). CONCLUSION: The high incidence of acetabular retroversion, determined by the COS, shows that this anatomic configuration may not differ in frequency between asymptomatic individuals and patients with symptomatic femoroacetabular impingement (FAI). Patients presenting with hip pain and evidence of FAI should be subjected to strict diagnostic scrutiny and evaluated in the sum of their clinical and radiological presentation. In our cohort of asymptomatic adults, the COS showed a higher incidence than the PWS or a combined COS/PWS. Cite this article: Bone Joint J 2017;99-B:1584-9.


Subject(s)
Acetabulum/diagnostic imaging , Bone Retroversion/diagnostic imaging , Femoracetabular Impingement/diagnostic imaging , Adolescent , Adult , Female , Hip Joint/diagnostic imaging , Humans , Imaging, Three-Dimensional , Joint Diseases/diagnostic imaging , Male , Prevalence , Tomography, X-Ray Computed , Young Adult
10.
Electrophoresis ; 38(11): 1475-1482, 2017 06.
Article in English | MEDLINE | ID: mdl-28401635

ABSTRACT

The quest for new cell-free DNA and exosome biomarker-based molecular diagnostics require fast and efficient sample preparation techniques. Conventional methods for isolating these biomarkers from blood are both time-consuming and laborious. New electrokinetic microarray devices using dielectrophoresis (DEP) to isolate cell-free DNA and exosome biomarkers have now greatly improved the sample preparation process. Nevertheless, these devices still have some limitations when used with high conductance biological fluids, e.g. blood, plasma, and serum. This study demonstrates that electrochemical damage may occur on the platinum electrodes of DEP microarray devices. It further examines two model device designs that include a parallel wire arrangement and a planar array. Effective isolation of fluorescent beads with parallel wires is shown under low-conductance conditions (10-4  S/m), but electrothermal flow overcomes DEP forces under high conductance conditions (>0.1 S/m). Planar devices are shown to be effective under high conductance conditions (∼1 S/m) without the deleterious effects of electrothermal flow. This study provides new insights into design compromises and limitations for producing future electrokinetic devices for better performance with high conductance solutions.


Subject(s)
DNA/isolation & purification , Electric Conductivity , Equipment Design , Exosomes , Lab-On-A-Chip Devices , Animals , Antibodies, Monoclonal , Biomarkers/analysis , Computer Simulation , DNA/blood , Equipment Design/instrumentation , Equipment Design/methods , Fluorescent Dyes , Humans , Kinetics , Mice , Microelectrodes , Models, Theoretical , Neoplasms/blood , Platinum , Polytetrafluoroethylene , Solutions
11.
Br J Dermatol ; 177(4): 1074-1085, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28417469

ABSTRACT

BACKGROUND: Oesophageal involvement of mucous membrane pemphigoid (MMP) has not yet been thoroughly described. OBJECTIVES: To characterize systematically the endoscopic lesions of a series of patients with oesophageal symptoms seen at a referral centre for autoimmune bullous diseases. METHODS: Clinical, endoscopic and immunological findings of consecutively referred patients with MMP with oesophageal involvement, systemic and endoscopic treatments, and follow-up are described. RESULTS: Of 477 consecutive patients with MMP consulting between 2002 and 2012, 26 (5·4%) had symptomatic oesophageal involvement. Dysphagia, observed in 23 (88%) patients, was the most frequent symptom. Oesophageal symptoms could be the first sign of MMP. Patients with oesophageal involvement had a mean of three other involved sites. At initial oesophageal endoscopy, 17 of 26 patients had active lesions (intact bullae, erosions and/or erythema), 15 had stricture(s) and 12 had other cicatricial lesions. Systemic therapy alone achieved oesophageal symptom relief for five patients. Dilatation was combined with systemic therapy for 12 patients and was successful in nine; one perforation occurred. CONCLUSIONS: Symptomatic oesophageal involvement affected 5·4% of patients with MMP. Dermatologists and gastroenterologists should be aware of these mucocutaneous diseases and their oesophageal involvement, as it could lead to earlier diagnosis and better care. Oesophageal dilatation could be a therapeutic option for symptomatic stricture not relieved by optimized systemic therapy alone.


Subject(s)
Esophageal Diseases/etiology , Pemphigoid, Benign Mucous Membrane/complications , Adolescent , Adult , Aged , Aged, 80 and over , Deglutition Disorders/etiology , Deglutition Disorders/surgery , Dilatation/methods , Esophageal Diseases/surgery , Esophagoscopy/methods , Female , Humans , Male , Middle Aged , Mouth Diseases/etiology , Mouth Diseases/surgery , Young Adult
12.
Australas Phys Eng Sci Med ; 40(2): 441-447, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28258484

ABSTRACT

The provision of sufficient chest compression is among the most important factors influencing patient survival during cardiopulmonary resuscitation (CPR). One approach to optimize the quality of chest compressions is to use mechanical-resuscitation devices. The aim of this study was to compare a new device for chest compression (corpuls cpr) with an established device (LUCAS II). We used a mechanical thorax model consisting of a chest with variable stiffness and an integrated heart chamber which generated blood flow dependent on the compression depth and waveform. The method of blood-flow generation could be changed between direct cardiac-compression mode and thoracic-pump mode. Different chest-stiffness settings and compression modes were tested to generate various blood-flow profiles. Additionally, an endurance test at high stiffness was performed to measure overall performance and compression consistency. Both resuscitation machines were able to compress the model thorax with a frequency of 100/min and a depth of 5 cm, independent of the chosen chest stiffness. Both devices passed the endurance test without difficulty. The corpuls cpr device was able to generate about 10-40% more blood flow than the LUCAS II device, depending on the model settings. In most scenarios, the corpuls cpr device also generated a higher blood pressure than the LUCAS II. The peak compression forces during CPR were about 30% higher using the corpuls cpr device than with the LUCAS II. In this study, the corpuls cpr device had improved blood flow and pressure outcomes than the LUCAS II device. Further examination in an animal model is required to prove the findings of this preliminary study.


Subject(s)
Cardiopulmonary Resuscitation/instrumentation , Mechanical Phenomena , Models, Biological , Pressure , Thorax/physiology , Compressive Strength
13.
Clin Radiol ; 72(1): 93.e1-93.e6, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27633725

ABSTRACT

AIM: To perform an intra-individual comparison of the frequency of respiratory-motion artefacts on magnetic resonance imaging (MRI) in cirrhotic patients following injection of gadoxetate disodium and gadobenate dimeglumine. MATERIALS AND METHODS: Ninety-five cirrhotic patients (61 men and 34 women, mean age 58 years) underwent liver MRI with intravenous administration of gadoxetate disodium and gadobenate dimeglumine at different times (interval between studies, 189±83 days). Three readers scored the severity of respiratory-motion artefacts on the three-dimensional (3D) gradient-echo (GRE) images acquired before and after contrast medium injection. McNemar's test was used to assess the difference in frequency of new respiratory-motion artefacts and transient severe motion (TSM) artefacts between gadoxetate disodium and gadobenate dimeglumine MRI studies. The association between clinical and technical features and the occurrence of TSM on gadoxetate disodium MRI studies was investigated. RESULTS: On arterial phase images, new respiratory-motion artefacts were present in 32/95 (34%) cases after injection of gadoxetate disodium, while only seen in 2/95 (2%) cases after injection of gadobenate dimeglumine (p<0.0001). TSM was present in 6/95 (6%) cases after injection of gadoxetate disodium, and in 0/95 (0%) case after injection of gadobenate dimeglumine. No clinical or technical features were associated with the occurrence of TSM. CONCLUSIONS: In cirrhotic patients, respiratory-motion artefacts on arterial phase 3D GRE images are more frequently seen after injection of gadoxetate disodium than after injection of gadobenate dimeglumine.


Subject(s)
Artifacts , Gadolinium DTPA/administration & dosage , Liver Cirrhosis/diagnostic imaging , Magnetic Resonance Imaging/methods , Meglumine/analogs & derivatives , Organometallic Compounds/administration & dosage , Respiratory Mechanics , Contrast Media/administration & dosage , Female , Humans , Image Enhancement/methods , Injections, Intravenous , Liver/diagnostic imaging , Longitudinal Studies , Male , Meglumine/administration & dosage , Middle Aged , Motion , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity
14.
Biomed Res Int ; 2017: 5470406, 2017.
Article in English | MEDLINE | ID: mdl-29392137

ABSTRACT

According to the European Resuscitation Council guidelines, the use of mechanical chest compression devices is a reasonable alternative in situations where manual chest compression is impractical or compromises provider safety. The aim of this study is to compare the performance of a recently developed chest compression device (Corpuls CPR) with an established system (LUCAS II) in a pig model. Methods. Pigs (n = 5/group) in provoked ventricular fibrillation were left untreated for 5 minutes, after which 15 min of cardiopulmonary resuscitation was performed with chest compressions. After 15 min, defibrillation was performed every 2 min if necessary, and up to 3 doses of adrenaline were given. If there was no return of spontaneous circulation after 25 min, the experiment was terminated. Coronary perfusion pressure, carotid blood flow, end-expiratory CO2, regional oxygen saturation by near infrared spectroscopy, blood gas, and local organ perfusion with fluorescent labelled microspheres were measured at baseline and during resuscitation. Results. Animals treated with Corpuls CPR had significantly higher mean arterial pressures during resuscitation, along with a detectable trend of greater carotid blood flow and organ perfusion. Conclusion. Chest compressions with the Corpuls CPR device generated significantly higher mean arterial pressures than compressions performed with the LUCAS II device.


Subject(s)
Coronary Circulation/physiology , Heart Arrest/physiopathology , Thorax/physiopathology , Ventricular Fibrillation/physiopathology , Animals , Arterial Pressure/physiology , Cardiopulmonary Resuscitation/methods , Chest Wall Oscillation/instrumentation , Disease Models, Animal , Hemodynamics , Humans , Swine
15.
Biomaterials ; 77: 207-15, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26606446

ABSTRACT

Artificial generated buccal mucosa equivalents are a promising approach for the reconstruction of urethral defects. Limiting in this approach is a poor blood vessel supply after transplantation, resulting in increased morbidity and necrosis. We generated a pre-vascularized buccal mucosa equivalent in a tri-culture of primary buccal epithelial cells, fibroblasts and microvascular endothelial cells, using a native collagen membrane as a scaffold. A successful pre-vascularization and dense formation of capillary-like structures at superficial areas was demonstrated. The lumen size of pre-formed blood vessels corresponded to the capillary size in vivo (10-30 µm). Comparing native with a highly cross-linked collagen membrane we found a distinct higher formation of capillary-like structures on the native membrane, apparently caused by higher secretion of angiogenic factors such as PDGF, IL-8 and angiopoietin by the cells. These capillary-like structures became functional blood vessels through anastomosis with the host vasculature after implantation in nude mice. This in vitro method should result in an accelerated blood supply to the biomaterial with cells after transplantation and increase the succes rates of the implant material.


Subject(s)
Endothelial Cells/cytology , Epithelial Cells/cytology , Fibroblasts/cytology , Mouth Mucosa , Organoids/blood supply , Tissue Engineering/methods , Transplants/blood supply , Angiogenesis Inducing Agents/analysis , Animals , Capillaries/cytology , Capillaries/growth & development , Cells, Cultured , Coculture Techniques , Collagen , Foreskin/cytology , Gingiva/cytology , Heterografts , Humans , Male , Membranes, Artificial , Mice , Mice, Nude , Organoids/cytology , Platelet Endothelial Cell Adhesion Molecule-1/analysis , Tissue Scaffolds
16.
Urologe A ; 54(8): 1105-7, 2015 Aug.
Article in German | MEDLINE | ID: mdl-26246208

ABSTRACT

For reconstructive interventions on the urethra the use of autologous buccal mucosa has a proven value. The aim of this study was to generate an in vitro preparation which is already infiltrated by capillary-like structures and is more rapidly incorporated after implantation. Commercially available collagen matrices which have been approved for use in humans were used as the substrate. Application possibilities of such artificial tissue in addition to reconstruction of the urethra include coverage of large defects in the oral, neck, nasal and aural areas, in gynecology and in ophthalmology.


Subject(s)
Mouth Mucosa/blood supply , Mouth Mucosa/transplantation , Plastic Surgery Procedures/instrumentation , Tissue Engineering/methods , Urethra/growth & development , Urethra/surgery , Humans , Regeneration , Tissue Scaffolds
17.
Eur J Radiol ; 84(11): 2269-74, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26283192

ABSTRACT

PURPOSE: In patients with multiple myeloma (MM), computed tomography is widely used for staging and to detect fractures. Detecting patients at severe fracture risk is of utmost importance. However the criteria for impaired stability of vertebral bodies are not yet clearly defined. We investigated the performance of parameters that can be detected by the radiologist for discrimination of patients with and without fractures. METHODS AND MATERIALS: We analyzed 128 whole body low-dose CT of MM patients. In all scans a QCT calibration phantom was integrated into the positioning mat (Image Analysis Phantom(®)). A QCT-software (Structural Insight) performed the volumetric bone mineral density (vBMD) measurements. Description of fracture risk was provided from the clinical radiological report. Suspected progressive disease (PD) was reported by the referring clinicians. Two radiologists that were blinded to study outcome reported on the following parameters based on predefined criteria: reduced radiodensity in the massa lateralis of the os sacrum (RDS), trabecular thickening and sclerosis of three or more vertebrae (TTS), extraosseous MM manifestations (EOM), visible small osteolytic lesions up to a length of 8mm (SO) and osteolytic lesions larger than 8mm (LO). Prevalent vertebral fractures (PVF) were defined by Genant criteria. Age-adjusted standardized odds ratios (sOR) per standard deviation change were derived from logistic regression analysis and area under the curve (AUC) from receiver operating characteristics (ROC) analyses were calculated. ROC curves were compared using the DeLong method. RESULTS: 45% of the 128 patients showed PVF (29 of 75 men, 24 of 53 women). Patients with PVF were not significantly older than patients without fractures (64.6 ± 9.2 vs. 63.3 ± 12.3 years: mean ± SD, p=0.5). The prevalence of each parameter did not differ significantly by sex. Significant fracture discrimination for age adjusted single models was provided by the parameters vBMD (OR 3.5 [1.4-8.8], AUC=0.64 ± 0.14), SO (sOR 1.6[1.1-2.2], AUC=0.63 ± 0.05), LO (sOR 2.1[1.1-4.2] AUC=0.69 ± 0.05) and RDS (sOR 2.6[1.6-4.7], AUC=0.69 ± 0.05). Multivariate models of these four parameters showed a significantly stronger association with the development of PVF (AUC=0.80 ± 0.04) than single variables. TTS showed a significant association with PVF in men(sOR 1.5 [0.8-3.0], AUC=0.63 ± 0.08), but not in women (sOR 2.3[1.4-3.7], AUC=0.70 ± 0.07). PD was significantly associated with PVF in women (sOR 1.9[1.1-3.6], AUC=0.67 ± 0.08) but not in men (sOR 1.4[0.9-2.3], AUC=0.57 ± .07). EOM were not associated with PVF (sOR 1.0[0.4-2.6], AUC=0.51 ± .05). CONCLUSION: In multiple myeloma, focal skeletal changes in low dose CT scans show a significant association with prevalent vertebral fractures. The combination of large osteolytic lesions and loss in radiodensity as can be detected with simple CT Hounsfield measurements of the os sacrum or BMD measurements showed the strongest association to fractures and may be of value for prospective studies.


Subject(s)
Bone Density , Multiple Myeloma/complications , Osteolysis/complications , Osteolysis/diagnostic imaging , Spinal Fractures/complications , Spinal Fractures/diagnostic imaging , Adult , Aged , Aged, 80 and over , Area Under Curve , Cross-Sectional Studies , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/pathology , Male , Middle Aged , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/pathology , Osteoporotic Fractures , Prevalence , ROC Curve , Sclerosis , Spinal Fractures/pathology , Tomography, X-Ray Computed/methods
18.
Clin Radiol ; 70(6): 661-6, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25782338

ABSTRACT

A Dieulafoy lesion describes a tortuous, submucosal artery in the gastrointestinal tract--most commonly the posterior stomach--that penetrates through the mucosa over time, eventually perforating to cause severe gastrointestinal bleeding. Due to its insidious onset, tendency to cause intermittent but severe bleeding, and difficulty of endoscopic diagnosis, Dieulafoy lesion has a very high mortality rate. Although originally thought not to be a radiologically diagnosable entity, Dieulafoy lesions can be seen at enhanced CT of the abdomen. The purpose of this review is to summarize the pathophysiology, epidemiology, diagnosis, and management of Dieulafoy lesions with a focus on diagnostic findings at enhanced CT imaging.


Subject(s)
Arteries/abnormalities , Gastrointestinal Hemorrhage/diagnostic imaging , Joint Instability/diagnostic imaging , Skin Diseases, Genetic/diagnostic imaging , Vascular Malformations/diagnostic imaging , Adult , Aged , Diagnosis, Differential , Duodenal Diseases/diagnostic imaging , Duodenal Diseases/etiology , Duodenal Diseases/surgery , Esophageal Diseases/diagnostic imaging , Esophageal Diseases/etiology , Esophageal Diseases/surgery , Female , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/surgery , Humans , Joint Instability/complications , Male , Skin Diseases, Genetic/complications , Stomach Diseases/diagnostic imaging , Stomach Diseases/etiology , Stomach Diseases/surgery , Tomography, X-Ray Computed , Vascular Malformations/complications
19.
Clin Radiol ; 69(10): 1072-6, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25110301

ABSTRACT

A duodenal diverticulum is a commonly encountered entity in gastrointestinal radiology with a wide variety of appearances. The purpose of this review is to describe the normal anatomy and embryology of the duodenum, discuss the differences between a true versus intraluminal duodenal diverticulum, and to highlight the normal appearance, potential complications, and imaging pitfalls of duodenal diverticula.


Subject(s)
Diagnostic Imaging/methods , Diverticulum/complications , Diverticulum/diagnosis , Duodenal Diseases/complications , Duodenal Diseases/diagnosis , Abdominal Pain/etiology , Aged , Cholangiopancreatography, Magnetic Resonance/methods , Diverticulitis/etiology , Duodenum/anatomy & histology , Duodenum/diagnostic imaging , Duodenum/pathology , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Tomography, X-Ray Computed/methods
20.
Med Eng Phys ; 36(7): 889-95, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24780754

ABSTRACT

The in vivo quantification of rotational laxity of the knee joint is of importance for monitoring changes in joint stability or the outcome of therapies. While invasive assessments have been used to study rotational laxity, non-invasive methods are attractive particularly for assessing young cohorts. This study aimed to determine the conditions under which tibio-femoral rotational laxity can be assessed reliably and accurately in a non-invasive manner. The reliability and error of non-invasive examinations of rotational joint laxity were determined by comparing the artefact associated with surface mounted markers against simultaneous measurements using fluoroscopy in five knees including healthy and ACL deficient joints. The knees were examined at 0°, 30°, 60° and 90° flexion using a device that allows manual axial rotation of the joint. With a mean RMS error of 9.6°, the largest inaccuracy using non-invasive assessment was present at 0° knee flexion, whereas at 90° knee flexion, a smaller RMS error of 5.7° was found. A Bland and Altman assessment indicated that a proportional bias exists between the non-invasive and fluoroscopic approaches, with limits of agreement that exceeded 20°. Correction using average linear regression functions resulted in a reduction of the RMS error to below 1° and limits of agreement to less than ±1° across all knees and flexion angles. Given the excellent reliability and the fact that a correction of the surface mounted marker based rotation values can be achieved, non-invasive evaluation of tibio-femoral rotation could offer opportunities for simplified devices for use in clinical settings in cases where invasive assessments are not justified. Although surface mounted marker based measurements tend to overestimate joint rotation, and therefore joint laxity, our results indicate that it is possible to correct for this error.


Subject(s)
Arthrometry, Articular/instrumentation , Artifacts , Fiducial Markers , Joint Instability/diagnosis , Joint Instability/physiopathology , Knee Injuries/diagnosis , Knee Injuries/physiopathology , Equipment Design , Equipment Failure Analysis , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity
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