Background Cholinergic receptors, discovered on bone cells suggest that the cholinergic nervous s... more Background Cholinergic receptors, discovered on bone cells suggest that the cholinergic nervous system may play a regulatory role also in bone metabolism. Our previous experiments have confirmed the presence of nicotinic acetylcholine receptor subunits on osteoclasts, and have revealed that the α7 nicotinic acetylcholine receptor plays a key role in the regulation of osteoclastogenesis in vitro. Objectives To evaluate the role of the α7 nicotinic acetylcholine receptor in bone homeostasis in vivo. Methods We analyzed the bone phenotype of α7 nicotinic acetylcholine receptor knockout mice (α7 nAChR-/- mice). We investigated the bone phenotype of C57/BL6 α7 nAChR-/- mice as well as sex- and age-matched littermates. For bone mineral density (BMD) measurements we evaluated the proximal tibia and BMD values were calculated by using dual energy X-ray absorptiometry (DEXA). Bone phenotype was further evaluated by histomorphometrical analysis using 2-μm decalcified paraffin-embedded section...
Background Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial ... more Background Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and osteoclast mediated bone erosions. AlphaVbeta3 (αvβ3) Integrin is highly expressed in osteoclasts and its inhibition disturbs osteoclast function in vivo. However, the role of αvβ3 Integrin in the development of collagen induced arthritis (CIA), a well established model for human RA, has not been examined extensively. Objectives To study the role of the αvβ3 inhibitor cilengitide, an Arginine-Glycine-Asparagine amino acid peptide (RGD peptide), on osteoclastogenesis in vitro and to assess its efficacy in preventing CIA in vivo. Methods For in vitro validation of osteoclastogenesis mouse bone marrow derived cells were differentiated into tartrate-resistant acid phosphatase positive (TRAP+) mononuclear osteoclasts (pre-osteoclasts) and TRAP+ multinucleated mature osteoclasts in the presence of macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear f...
ABSTRACT Background Education and training related to rheumatic and musculoskeletal diseases are ... more ABSTRACT Background Education and training related to rheumatic and musculoskeletal diseases are one of the key strategic areas of EULAR. To better understand the educational needs of young clinicians and/or researchers in rheumatology, the Emerging EULAR Network (EMEUNET) and the EULAR Standing Committee on Education and Training (ESCET) developed an educational survey. Methods Students, clinicians and/or researchers below the age of 40 who work in the field of rheumatology were invited to participate in an online-based survey. Invitations were sent to 763 EMEUNET members and young individuals of national organizations. The current abstract presents an interim analysis. Results 458 participants completed the survey. The majority of participants were between 31 and 35 years old (43%), female (66%) and from Europe (91%). Spain (18%), but also the UK, Czech Republic and Portugal (all around 8%) were very well represented. Most participants were trainees in rheumatology (46%) or served as junior faculty (33%). Participants spent a mean of 59% of their time in clinical work and 26% in research, but little in educational and administrative work. While participants mainly performed clinical and/or epidemiological research (63%), scientific foci as defined by ARD key-words varied greatly. Asked for career plans, around 78% of participants intended to work in academia or hospital settings with a lower interest in industry or private practice. A central goal of the survey was to assess the awareness and acceptance of existing EULAR educational opportunities. While 78% of participants were familiar with the role of EMEUNET, relatively little was known about ESCET. Of note, the current EULAR educational portfolio covered well the needs of more than 70% of participants. The various EULAR online courses and the EULAR postgraduate course received the highest ratings considering past participations or current interest. In detail, 28% and 12% of responders had already participated in the EULAR online course on rheumatic diseases and in the EULAR postgraduate course, respectively. Limited funding, either through personal means (58%) or through the home institution (45%), was considered the major obstacle to participate in existing programs. The second major objective of the survey was to determine the educational needs and preferences of young clinicians and researchers in the field. Clinically, more than 90% of participants were interested in receiving training in imaging techniques as well as in general disease review courses. Regarding scientific training, more than 80% of participants were interested in acquiring statistics, presentation, writing and/or reviewing skills. Participants gave very diverse answers regarding preferred learning modalities: most individuals favored live courses or online learning tools over textbooks and lectures as well as case-oriented over systematic learning. Conclusions The EMEUNET/ESCET educational survey was very well-received among young individuals in the field or rheumatology with excellent participation. While the current EULAR educational portfolio is well appreciated, lack of funding may limit the access to it. This new data will help EULAR to adapt their educational portfolio to the needs of young clinicians and researchers. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3015
2011 IEEE 7th International Conference on Intelligent Computer Communication and Processing, 2011
Complex Event Processing (CEP) is a powerful technology for implementing real time applications. ... more Complex Event Processing (CEP) is a powerful technology for implementing real time applications. It offers efficient processing of occurring information pieces, so called events, based on an architecture that provides strong decoupling of its components: event producer, event processors and event consumer (4). For this CEP is seen as an important contribution in future information systems. CEP applications already have
To produce consensus-based definitions of the US elementary lesions in gout and to test their rel... more To produce consensus-based definitions of the US elementary lesions in gout and to test their reliability in a web-based exercise. The process consisted of two steps. In the first step a written Delphi questionnaire was developed from a systematic literature review and expert international consensus. This collated information resulted in four statements defining US elementary lesions: double contour (DC), tophus, aggregates and erosion. The Delphi questionnaire was sent to 35 rheumatology experts in US, asking them to rate their level of agreement or disagreement with each statement. The second step tested the reliability by a web-exercise. US images of both normal and gouty elementary lesions were collected by the participants. A facilitator then constructed an electronic database of 110 images. The database was sent to the participants, who evaluated the presence/absence of US elementary lesions. A group of 20 images was displayed twice to evaluate intra-reader reliability. A tota...
ABSTRACT Objectives To correlate cartilage thickness as measured by ultrasound (US) with joint sp... more ABSTRACT Objectives To correlate cartilage thickness as measured by ultrasound (US) with joint space narrowing (JSN) and joint space width (JSW) as measured by conventional radiography in the metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis. To validate US for measuring cartilage thickness, cadaver specimens of MCP joints were evaluated by US and by anatomical measurement. Methods Bilateral MCP 2-5 joints of 35 consecutive patients (280 joints) recruited in our outpatient clinic who had conventional radiographs (<1 years) of both hands available as well as cadaver specimens of MCP 2-5 joints (n:12) were included in the analysis. The cartilage layer of the metacarpal heads and proximal phalangeal bases 2-5 of included patients as well as of cadavers were assessed bilaterally using a 15 Mhz linear transducer (GE Logic E9) from dorsal longitudinal and transverse views in midline by 2 sonographers blinded to clinical/radiographic data. Cartilage thickness was measured in cm with an integrated caliper on static US images. Both JSW and JSN were evaluated on conventional posterior-anterior radiographs. JSW was quantified as the shortest distance betweenthe subchondral bone plates using a standard measurementtool, while JSN was evaluated using the van der Heijde modified Sharp scoring method (vdHS). Ankylosed and luxated joints were excluded from the analysis. Anatomical metacarpal cartilage thickness (MCT) was also evaluated on static digital images of fresh frozen cadaver specimens, split in the mid-sagittal plane. Cartilage thickness was correlated with x-ray findings using Spearman’s or Pearson’s correlation. Intra- and interobserver reliability of US, and agreement between US and anatomic measurements were assessed by estimating the intraclass correlation coefficient (ICC). Results In the patient population mean age was 63.1±11.3 years, mean disease duration was 10.6±7.8 years, mean CDAI was 8.1±7.3; 82.9% were female and 51% were rheumatoid factor positive. US measurement of MCT of MCP 2-5 was 0,42+/-0,19 mm. MCT of individual joints of the left and right hand correlated with individual MCP JSN (r=-0.799 and -0.702 respectively, p<0.01) and individual MCP JSW (r=0.588 and 0.401 respectively, p<0.01). The sum score of MCT for MCP joint 2-5 correlated with total MCP JSW (r=0.771, p<0.01), total JSN (r=-0.412, p<0.05), sum erosion score of the vdHS (r=-0.500, p<0.01) and the total vdHS (r=-0.576, p<0.01). No correlation was found between phalangeal cartilage thickness and JSN or JSW. Intra- and interobserver reliability of the US measurement of MCT in the clinical cohort and in the cadavers was 0.77 and 0.62, and 0.91 and 0.75 respectively. Agreement between US and anatomic measurement of MCT on cadaver specimens of MCP joints was 0.62. Conclusions Both JSW and JSN by radiography indeed represent cartilage thickness at least in MCP joints. US is a valid tool for measuring MCT. Phalangeal cartilage thickness has no added value beyond the measurement of MCT. When radiographic scoring is not available, US measurement of MCT might be a feasible alternative to depict cartilage damage in patients with RA. Disclosure of Interest None Declared
ABSTRACT Background The detection of intraarticular Power Doppler (PD) signal in metacarpophalang... more ABSTRACT Background The detection of intraarticular Power Doppler (PD) signal in metacarpophalangeal (MCP) joints may play a key role in the assessment of patients with early arthritis. Currently used quantification methods for PD however do not provide information related to the intraarticular topographic distribution of the signal. The evaluation of PD signal in the MCP joint is further hindered by the fact that new, highly sensitive PD systems allow the detection of normal PD signal in the MCP joints of healthy subjects, likely corresponding to physiological feeding vessels. Objectives Our aim within this pilot investigation was to identify different patterns of intraarticular PD signal in the MCP joint based on its topographic location and to demonstrate the presence of physiological feeding vessels in cadaver preparations obtained with corrosion and also in histological sections. Methods We evaluated a panel of one hundred images obtained at MCP joint level in both healthy subjects and patients with early arthritis using dorsal longitudinal and transverse views. The presence of physiological vessels in the metacarpal head was evaluated in cadaver specimens subjected to corrosion, while those in the dorsal fat pad were demonstrated in histological sections obtained from cadavers of patients, with negative case histories for diseases involving the small joints of the hand. Results We identified at least two distinct patterns of intraarticular PD signal: pattern 1 (extrasynovial) was characterized by intraarticular, but not intrasynovial PD signal while pattern 2 (intrasynovial) was characterized by intraarticular and intrasynovial PD signal in structures possessing a synovial lining. Both patterns could be demonstrated in healthy individuals and also in patients with early arthritis. We also confirmed the presence of physiological vessels in the metacarpal head as well as in the dorsal fat pad of cadavers. Conclusions Extrasynovial PD signal may be due to the vasodilation of pre-existing feeding vessels in intraarticular areas that do not possess a synovial lining, e.g. the dorsal fat pad as often seen in patients with early arthritis. Intrasynovial PD signal may correspond to the presence of physiological feeding vessels at the metacarpal head seen in healthy individuals, similar signals however may also be detected in patients with erosive disease. The evaluation of intraarticular PD signal in the MCP joint therefore remains problematic, especially in cases where grey-scale changes characteristic to synovitis are lacking. Disclosure of Interest None Declared
A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists f... more A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations wer...
A két-foton mikroszkópia használata új információkat szolgáltatott a nemszinaptikus kölcsönhatáso... more A két-foton mikroszkópia használata új információkat szolgáltatott a nemszinaptikus kölcsönhatásokról szubmikronos anatómiai struktúrákban. Feltérképeztük a technika felhasználásának lehetőségeit a különböző szövetpreparátumok, idegsejttípusok esetében. A membrán Na+/Ca2+ cserélő gátlása elsősorban a dendrittörzsben befolyásolja a szinaptikus Ca2+ tranzienseket, és szabályozza a tüske-dendrit kapcsolatot. A dendritikus Ca2+ válaszok szintjén a noradrenalin pozitív hatású a dendritikus integráció kapacitásaira nézve, elősegíti a dendritikus potenciálok keletkezését, előnyös a munkamemóriára nézve. Kísérleteink feltárták a nikotin sokrétű serkentő hatásait a dendritek funkcióira nézve, így az akciós potenciálok terjedésének erősítését, spontán válaszok kialakulását a piramissejtek tüskéiben, illetve az interneuronok dendrittörzsében. A farmakológiai alkalmazások közül az antidepresszánsok hatásait vizsgáltuk. Elképzelhető, hogy az antidepresszánsok a lassú inaktivált állapot stabilizá...
Kutatási projektünk elsődleges célja az volt, hogy megpróbáljuk felderíteni a depresszió hatteréb... more Kutatási projektünk elsődleges célja az volt, hogy megpróbáljuk felderíteni a depresszió hatterében álló neurokémiai történéseket. Munkánk során megállapítottuk, hogy a jelenleg használt antidepresszánsok a monoamin szintek befolyásolásán kívül egyéb mechanizmusokkal (a nikotinikus acetilkolin receptorok és az NMDA receptorok, valamint a feszültségfüggő Na+-csatornák gátlásán kesresztül) is módosíthatják a központi idegrendszer működését, mely hatások hozzájárulhatnak az antidepresszáns hatás kifejlődéséhez. Kidolgoztuk az antidepresszánsok egy új osztályának, az aktív antidepresszánsoknak az elméleti alapjait, valamint leírtuk a monoamin transzporterek egy érdekes tulajdonságát, a szerotonin transzporterek heterológ noradrenalin felvételi képességét. Ez a felismerésünk rávilágít az átfedő monoaminerg rendszerek közötti szoros együttműködésre és elősegítheti az szelektív szerotonin reuptake inhibítor vegyületek hatásmechanizmusának jobb megértését. Eredményeink felhasználásával köze...
The aim of this study was to verify the presence of presynaptic nicotinic acetylcholine receptors... more The aim of this study was to verify the presence of presynaptic nicotinic acetylcholine receptors (nAChRs) at the terminals of myenteric motoneurons using a potent and highly selective nicotinic agonist, epibatidine. We examined contraction, and release of [3H]ACh on a guinea-pig longitudinal muscle strip preparation. First, we compared the ability of epibatidine and nicotine to induce isometric contraction and found epibatidine (EC50 = 23.1 nM) to be 300-fold more potent than nicotine (EC50 = 7.09 microM). The release and contraction induced by 30 nM epibatidine were inhibited by the nicotinic antagonist mecamylamine (3 microM) and the Na(+)-channel blocker TTX (1 microM), indicating that the effects are mediated via nAChRs and are fully dependent on the propagation of action potentials. Atropine (0.1 microM) significantly increased the [3H]ACh release but could not block contraction suggesting that a substantial part of the response develops via a noncholinergic mechanism. Epibati...
Objective To validate ultrasound (US) for measuring metacarpal cartilage thickness (MCT), by comp... more Objective To validate ultrasound (US) for measuring metacarpal cartilage thickness (MCT), by comparing it with anatomical measurement using cadaver specimens. To correlate US MCT with radiographic joint space narrowing ( JSN) or width ( JSW) in patients with rheumatoid arthritis (RA). Methods Bilateral metacarpophalangeal (MCP) joints of 35 consecutive outpatients, with recent hand X-rays, were included in the analysis. Metacarpal and phalangeal cartilage of MCP 2-5 was assessed bilaterally by US. JSW and JSN were evaluated on X-rays by the van der Heijde modified Sharp method (vdHS). In addition, cadaver specimens of MCP 2-5 joints (n=19) were evaluated by anatomical measurement and US. Results The agreement (intraclass correlation coefficient) between sonographic and anatomical MCT on cadaver specimens of MCP joints was 0.61. MCT of individual MCP joints correlated with individual MCP JSN (r=−0.32, p<0.001) and individual MCP JSW (r=0.72, p<0.001). No correlation was found between phalangeal cartilage thickness and JSN in individual MCP joints. The US MCT summary score for MCP joints 2-5 correlated with summary scores for JSW (r=0.78, p<0.001), JSN (r=−0.5, p<0.001), erosion score of the vdHS (r=−0.39, p<0.001) and total vdHS (r=−0.47, p<0.001). Conclusions Sonographic cartilage assessment in MCPs is closely related to anatomical cartilage thickness. Both JSW and JSN by radiography represent cartilage thickness in the MCP joints of patients with RA quite well. Thus, US is a valid tool for measuring MCT if radiographs are not available or in case of joint malalignment.
To explore perceptions of, participation in and satisfaction with mentoring programmes among youn... more To explore perceptions of, participation in and satisfaction with mentoring programmes among young clinicians and researchers in rheumatology in Europe. To identify mentoring needs and expectations focusing on gender-specific differences. A survey on mentoring in rheumatology was distributed to young clinicians and researchers in rheumatology in Europe through the EMEUNET network. We received 248 responses from 30 European countries. Although 82% of respondents expressed the need for a formal mentoring scheme by EULAR, only 35% participated in mentoring programmes and merely 20% were very satisfied with mentoring. Respondents very satisfied with mentoring were more likely to participate in research, but not clinical mentoring programmes. Career mentoring was perceived as the most beneficial type of mentoring for career development by 46% of respondents, only 35% of respondents, however, declared the existence of career mentoring programmes in their country. There was no gender diffe...
To analyse the similarities and discrepancies between the official rheumatology specialty trainin... more To analyse the similarities and discrepancies between the official rheumatology specialty training programmes across Europe. A steering committee defined the main aspects of training to be assessed. In 2013, the rheumatology official training programmes were reviewed for each of the European League Against Rheumatism (EULAR) countries and two local physicians independently extracted data on the structure of training, included competencies and assessments performed. Analyses were descriptive. 41 of the 45 EULAR countries currently provide specialist training in rheumatology; in the remaining four rheumatologists are trained abroad. 36 (88%) had a single national curriculum, one country had two national curricula and four had only local or university-specific curricula. The mean length of training programmes in rheumatology was 45 (SD 19) months, ranging between 3 and 72 months. General internal medicine training was mandatory in 40 (98%) countries, and was performed prior to and/or d...
ABSTRACT In this paper we introduce the open source testing system QCEP-TS for realizing executab... more ABSTRACT In this paper we introduce the open source testing system QCEP-TS for realizing executable acceptance test driven development (EATDD) of complex event processing (CEP) applications. We will motivate the need of EATDD in this domain and argue that state of the art solutions do not address this topic or have substantial weaknesses. We show the design approach of our testing system including a vendor independent testing syntax. We also state relevant challenges for testing CEP applications and discuss implementation details of our solution. On the basis of a real world scenario we demonstrate first practical experiences of our solution. QCEP-TS is available as open source project at http://sourceforge.net/p/qcep-ts. QCEP (Quality Assurance of Complex Event Processing) is a collaboration project of the Munich University of Applied Sciences, the Technical University of Dresden and the UniCredit Business Integrated Solutions S.C.p.A.
Background Cholinergic receptors, discovered on bone cells suggest that the cholinergic nervous s... more Background Cholinergic receptors, discovered on bone cells suggest that the cholinergic nervous system may play a regulatory role also in bone metabolism. Our previous experiments have confirmed the presence of nicotinic acetylcholine receptor subunits on osteoclasts, and have revealed that the α7 nicotinic acetylcholine receptor plays a key role in the regulation of osteoclastogenesis in vitro. Objectives To evaluate the role of the α7 nicotinic acetylcholine receptor in bone homeostasis in vivo. Methods We analyzed the bone phenotype of α7 nicotinic acetylcholine receptor knockout mice (α7 nAChR-/- mice). We investigated the bone phenotype of C57/BL6 α7 nAChR-/- mice as well as sex- and age-matched littermates. For bone mineral density (BMD) measurements we evaluated the proximal tibia and BMD values were calculated by using dual energy X-ray absorptiometry (DEXA). Bone phenotype was further evaluated by histomorphometrical analysis using 2-μm decalcified paraffin-embedded section...
Background Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial ... more Background Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and osteoclast mediated bone erosions. AlphaVbeta3 (αvβ3) Integrin is highly expressed in osteoclasts and its inhibition disturbs osteoclast function in vivo. However, the role of αvβ3 Integrin in the development of collagen induced arthritis (CIA), a well established model for human RA, has not been examined extensively. Objectives To study the role of the αvβ3 inhibitor cilengitide, an Arginine-Glycine-Asparagine amino acid peptide (RGD peptide), on osteoclastogenesis in vitro and to assess its efficacy in preventing CIA in vivo. Methods For in vitro validation of osteoclastogenesis mouse bone marrow derived cells were differentiated into tartrate-resistant acid phosphatase positive (TRAP+) mononuclear osteoclasts (pre-osteoclasts) and TRAP+ multinucleated mature osteoclasts in the presence of macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear f...
ABSTRACT Background Education and training related to rheumatic and musculoskeletal diseases are ... more ABSTRACT Background Education and training related to rheumatic and musculoskeletal diseases are one of the key strategic areas of EULAR. To better understand the educational needs of young clinicians and/or researchers in rheumatology, the Emerging EULAR Network (EMEUNET) and the EULAR Standing Committee on Education and Training (ESCET) developed an educational survey. Methods Students, clinicians and/or researchers below the age of 40 who work in the field of rheumatology were invited to participate in an online-based survey. Invitations were sent to 763 EMEUNET members and young individuals of national organizations. The current abstract presents an interim analysis. Results 458 participants completed the survey. The majority of participants were between 31 and 35 years old (43%), female (66%) and from Europe (91%). Spain (18%), but also the UK, Czech Republic and Portugal (all around 8%) were very well represented. Most participants were trainees in rheumatology (46%) or served as junior faculty (33%). Participants spent a mean of 59% of their time in clinical work and 26% in research, but little in educational and administrative work. While participants mainly performed clinical and/or epidemiological research (63%), scientific foci as defined by ARD key-words varied greatly. Asked for career plans, around 78% of participants intended to work in academia or hospital settings with a lower interest in industry or private practice. A central goal of the survey was to assess the awareness and acceptance of existing EULAR educational opportunities. While 78% of participants were familiar with the role of EMEUNET, relatively little was known about ESCET. Of note, the current EULAR educational portfolio covered well the needs of more than 70% of participants. The various EULAR online courses and the EULAR postgraduate course received the highest ratings considering past participations or current interest. In detail, 28% and 12% of responders had already participated in the EULAR online course on rheumatic diseases and in the EULAR postgraduate course, respectively. Limited funding, either through personal means (58%) or through the home institution (45%), was considered the major obstacle to participate in existing programs. The second major objective of the survey was to determine the educational needs and preferences of young clinicians and researchers in the field. Clinically, more than 90% of participants were interested in receiving training in imaging techniques as well as in general disease review courses. Regarding scientific training, more than 80% of participants were interested in acquiring statistics, presentation, writing and/or reviewing skills. Participants gave very diverse answers regarding preferred learning modalities: most individuals favored live courses or online learning tools over textbooks and lectures as well as case-oriented over systematic learning. Conclusions The EMEUNET/ESCET educational survey was very well-received among young individuals in the field or rheumatology with excellent participation. While the current EULAR educational portfolio is well appreciated, lack of funding may limit the access to it. This new data will help EULAR to adapt their educational portfolio to the needs of young clinicians and researchers. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3015
2011 IEEE 7th International Conference on Intelligent Computer Communication and Processing, 2011
Complex Event Processing (CEP) is a powerful technology for implementing real time applications. ... more Complex Event Processing (CEP) is a powerful technology for implementing real time applications. It offers efficient processing of occurring information pieces, so called events, based on an architecture that provides strong decoupling of its components: event producer, event processors and event consumer (4). For this CEP is seen as an important contribution in future information systems. CEP applications already have
To produce consensus-based definitions of the US elementary lesions in gout and to test their rel... more To produce consensus-based definitions of the US elementary lesions in gout and to test their reliability in a web-based exercise. The process consisted of two steps. In the first step a written Delphi questionnaire was developed from a systematic literature review and expert international consensus. This collated information resulted in four statements defining US elementary lesions: double contour (DC), tophus, aggregates and erosion. The Delphi questionnaire was sent to 35 rheumatology experts in US, asking them to rate their level of agreement or disagreement with each statement. The second step tested the reliability by a web-exercise. US images of both normal and gouty elementary lesions were collected by the participants. A facilitator then constructed an electronic database of 110 images. The database was sent to the participants, who evaluated the presence/absence of US elementary lesions. A group of 20 images was displayed twice to evaluate intra-reader reliability. A tota...
ABSTRACT Objectives To correlate cartilage thickness as measured by ultrasound (US) with joint sp... more ABSTRACT Objectives To correlate cartilage thickness as measured by ultrasound (US) with joint space narrowing (JSN) and joint space width (JSW) as measured by conventional radiography in the metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis. To validate US for measuring cartilage thickness, cadaver specimens of MCP joints were evaluated by US and by anatomical measurement. Methods Bilateral MCP 2-5 joints of 35 consecutive patients (280 joints) recruited in our outpatient clinic who had conventional radiographs (&lt;1 years) of both hands available as well as cadaver specimens of MCP 2-5 joints (n:12) were included in the analysis. The cartilage layer of the metacarpal heads and proximal phalangeal bases 2-5 of included patients as well as of cadavers were assessed bilaterally using a 15 Mhz linear transducer (GE Logic E9) from dorsal longitudinal and transverse views in midline by 2 sonographers blinded to clinical/radiographic data. Cartilage thickness was measured in cm with an integrated caliper on static US images. Both JSW and JSN were evaluated on conventional posterior-anterior radiographs. JSW was quantified as the shortest distance betweenthe subchondral bone plates using a standard measurementtool, while JSN was evaluated using the van der Heijde modified Sharp scoring method (vdHS). Ankylosed and luxated joints were excluded from the analysis. Anatomical metacarpal cartilage thickness (MCT) was also evaluated on static digital images of fresh frozen cadaver specimens, split in the mid-sagittal plane. Cartilage thickness was correlated with x-ray findings using Spearman’s or Pearson’s correlation. Intra- and interobserver reliability of US, and agreement between US and anatomic measurements were assessed by estimating the intraclass correlation coefficient (ICC). Results In the patient population mean age was 63.1±11.3 years, mean disease duration was 10.6±7.8 years, mean CDAI was 8.1±7.3; 82.9% were female and 51% were rheumatoid factor positive. US measurement of MCT of MCP 2-5 was 0,42+/-0,19 mm. MCT of individual joints of the left and right hand correlated with individual MCP JSN (r=-0.799 and -0.702 respectively, p&lt;0.01) and individual MCP JSW (r=0.588 and 0.401 respectively, p&lt;0.01). The sum score of MCT for MCP joint 2-5 correlated with total MCP JSW (r=0.771, p&lt;0.01), total JSN (r=-0.412, p&lt;0.05), sum erosion score of the vdHS (r=-0.500, p&lt;0.01) and the total vdHS (r=-0.576, p&lt;0.01). No correlation was found between phalangeal cartilage thickness and JSN or JSW. Intra- and interobserver reliability of the US measurement of MCT in the clinical cohort and in the cadavers was 0.77 and 0.62, and 0.91 and 0.75 respectively. Agreement between US and anatomic measurement of MCT on cadaver specimens of MCP joints was 0.62. Conclusions Both JSW and JSN by radiography indeed represent cartilage thickness at least in MCP joints. US is a valid tool for measuring MCT. Phalangeal cartilage thickness has no added value beyond the measurement of MCT. When radiographic scoring is not available, US measurement of MCT might be a feasible alternative to depict cartilage damage in patients with RA. Disclosure of Interest None Declared
ABSTRACT Background The detection of intraarticular Power Doppler (PD) signal in metacarpophalang... more ABSTRACT Background The detection of intraarticular Power Doppler (PD) signal in metacarpophalangeal (MCP) joints may play a key role in the assessment of patients with early arthritis. Currently used quantification methods for PD however do not provide information related to the intraarticular topographic distribution of the signal. The evaluation of PD signal in the MCP joint is further hindered by the fact that new, highly sensitive PD systems allow the detection of normal PD signal in the MCP joints of healthy subjects, likely corresponding to physiological feeding vessels. Objectives Our aim within this pilot investigation was to identify different patterns of intraarticular PD signal in the MCP joint based on its topographic location and to demonstrate the presence of physiological feeding vessels in cadaver preparations obtained with corrosion and also in histological sections. Methods We evaluated a panel of one hundred images obtained at MCP joint level in both healthy subjects and patients with early arthritis using dorsal longitudinal and transverse views. The presence of physiological vessels in the metacarpal head was evaluated in cadaver specimens subjected to corrosion, while those in the dorsal fat pad were demonstrated in histological sections obtained from cadavers of patients, with negative case histories for diseases involving the small joints of the hand. Results We identified at least two distinct patterns of intraarticular PD signal: pattern 1 (extrasynovial) was characterized by intraarticular, but not intrasynovial PD signal while pattern 2 (intrasynovial) was characterized by intraarticular and intrasynovial PD signal in structures possessing a synovial lining. Both patterns could be demonstrated in healthy individuals and also in patients with early arthritis. We also confirmed the presence of physiological vessels in the metacarpal head as well as in the dorsal fat pad of cadavers. Conclusions Extrasynovial PD signal may be due to the vasodilation of pre-existing feeding vessels in intraarticular areas that do not possess a synovial lining, e.g. the dorsal fat pad as often seen in patients with early arthritis. Intrasynovial PD signal may correspond to the presence of physiological feeding vessels at the metacarpal head seen in healthy individuals, similar signals however may also be detected in patients with erosive disease. The evaluation of intraarticular PD signal in the MCP joint therefore remains problematic, especially in cases where grey-scale changes characteristic to synovitis are lacking. Disclosure of Interest None Declared
A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists f... more A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations wer...
A két-foton mikroszkópia használata új információkat szolgáltatott a nemszinaptikus kölcsönhatáso... more A két-foton mikroszkópia használata új információkat szolgáltatott a nemszinaptikus kölcsönhatásokról szubmikronos anatómiai struktúrákban. Feltérképeztük a technika felhasználásának lehetőségeit a különböző szövetpreparátumok, idegsejttípusok esetében. A membrán Na+/Ca2+ cserélő gátlása elsősorban a dendrittörzsben befolyásolja a szinaptikus Ca2+ tranzienseket, és szabályozza a tüske-dendrit kapcsolatot. A dendritikus Ca2+ válaszok szintjén a noradrenalin pozitív hatású a dendritikus integráció kapacitásaira nézve, elősegíti a dendritikus potenciálok keletkezését, előnyös a munkamemóriára nézve. Kísérleteink feltárták a nikotin sokrétű serkentő hatásait a dendritek funkcióira nézve, így az akciós potenciálok terjedésének erősítését, spontán válaszok kialakulását a piramissejtek tüskéiben, illetve az interneuronok dendrittörzsében. A farmakológiai alkalmazások közül az antidepresszánsok hatásait vizsgáltuk. Elképzelhető, hogy az antidepresszánsok a lassú inaktivált állapot stabilizá...
Kutatási projektünk elsődleges célja az volt, hogy megpróbáljuk felderíteni a depresszió hatteréb... more Kutatási projektünk elsődleges célja az volt, hogy megpróbáljuk felderíteni a depresszió hatterében álló neurokémiai történéseket. Munkánk során megállapítottuk, hogy a jelenleg használt antidepresszánsok a monoamin szintek befolyásolásán kívül egyéb mechanizmusokkal (a nikotinikus acetilkolin receptorok és az NMDA receptorok, valamint a feszültségfüggő Na+-csatornák gátlásán kesresztül) is módosíthatják a központi idegrendszer működését, mely hatások hozzájárulhatnak az antidepresszáns hatás kifejlődéséhez. Kidolgoztuk az antidepresszánsok egy új osztályának, az aktív antidepresszánsoknak az elméleti alapjait, valamint leírtuk a monoamin transzporterek egy érdekes tulajdonságát, a szerotonin transzporterek heterológ noradrenalin felvételi képességét. Ez a felismerésünk rávilágít az átfedő monoaminerg rendszerek közötti szoros együttműködésre és elősegítheti az szelektív szerotonin reuptake inhibítor vegyületek hatásmechanizmusának jobb megértését. Eredményeink felhasználásával köze...
The aim of this study was to verify the presence of presynaptic nicotinic acetylcholine receptors... more The aim of this study was to verify the presence of presynaptic nicotinic acetylcholine receptors (nAChRs) at the terminals of myenteric motoneurons using a potent and highly selective nicotinic agonist, epibatidine. We examined contraction, and release of [3H]ACh on a guinea-pig longitudinal muscle strip preparation. First, we compared the ability of epibatidine and nicotine to induce isometric contraction and found epibatidine (EC50 = 23.1 nM) to be 300-fold more potent than nicotine (EC50 = 7.09 microM). The release and contraction induced by 30 nM epibatidine were inhibited by the nicotinic antagonist mecamylamine (3 microM) and the Na(+)-channel blocker TTX (1 microM), indicating that the effects are mediated via nAChRs and are fully dependent on the propagation of action potentials. Atropine (0.1 microM) significantly increased the [3H]ACh release but could not block contraction suggesting that a substantial part of the response develops via a noncholinergic mechanism. Epibati...
Objective To validate ultrasound (US) for measuring metacarpal cartilage thickness (MCT), by comp... more Objective To validate ultrasound (US) for measuring metacarpal cartilage thickness (MCT), by comparing it with anatomical measurement using cadaver specimens. To correlate US MCT with radiographic joint space narrowing ( JSN) or width ( JSW) in patients with rheumatoid arthritis (RA). Methods Bilateral metacarpophalangeal (MCP) joints of 35 consecutive outpatients, with recent hand X-rays, were included in the analysis. Metacarpal and phalangeal cartilage of MCP 2-5 was assessed bilaterally by US. JSW and JSN were evaluated on X-rays by the van der Heijde modified Sharp method (vdHS). In addition, cadaver specimens of MCP 2-5 joints (n=19) were evaluated by anatomical measurement and US. Results The agreement (intraclass correlation coefficient) between sonographic and anatomical MCT on cadaver specimens of MCP joints was 0.61. MCT of individual MCP joints correlated with individual MCP JSN (r=−0.32, p<0.001) and individual MCP JSW (r=0.72, p<0.001). No correlation was found between phalangeal cartilage thickness and JSN in individual MCP joints. The US MCT summary score for MCP joints 2-5 correlated with summary scores for JSW (r=0.78, p<0.001), JSN (r=−0.5, p<0.001), erosion score of the vdHS (r=−0.39, p<0.001) and total vdHS (r=−0.47, p<0.001). Conclusions Sonographic cartilage assessment in MCPs is closely related to anatomical cartilage thickness. Both JSW and JSN by radiography represent cartilage thickness in the MCP joints of patients with RA quite well. Thus, US is a valid tool for measuring MCT if radiographs are not available or in case of joint malalignment.
To explore perceptions of, participation in and satisfaction with mentoring programmes among youn... more To explore perceptions of, participation in and satisfaction with mentoring programmes among young clinicians and researchers in rheumatology in Europe. To identify mentoring needs and expectations focusing on gender-specific differences. A survey on mentoring in rheumatology was distributed to young clinicians and researchers in rheumatology in Europe through the EMEUNET network. We received 248 responses from 30 European countries. Although 82% of respondents expressed the need for a formal mentoring scheme by EULAR, only 35% participated in mentoring programmes and merely 20% were very satisfied with mentoring. Respondents very satisfied with mentoring were more likely to participate in research, but not clinical mentoring programmes. Career mentoring was perceived as the most beneficial type of mentoring for career development by 46% of respondents, only 35% of respondents, however, declared the existence of career mentoring programmes in their country. There was no gender diffe...
To analyse the similarities and discrepancies between the official rheumatology specialty trainin... more To analyse the similarities and discrepancies between the official rheumatology specialty training programmes across Europe. A steering committee defined the main aspects of training to be assessed. In 2013, the rheumatology official training programmes were reviewed for each of the European League Against Rheumatism (EULAR) countries and two local physicians independently extracted data on the structure of training, included competencies and assessments performed. Analyses were descriptive. 41 of the 45 EULAR countries currently provide specialist training in rheumatology; in the remaining four rheumatologists are trained abroad. 36 (88%) had a single national curriculum, one country had two national curricula and four had only local or university-specific curricula. The mean length of training programmes in rheumatology was 45 (SD 19) months, ranging between 3 and 72 months. General internal medicine training was mandatory in 40 (98%) countries, and was performed prior to and/or d...
ABSTRACT In this paper we introduce the open source testing system QCEP-TS for realizing executab... more ABSTRACT In this paper we introduce the open source testing system QCEP-TS for realizing executable acceptance test driven development (EATDD) of complex event processing (CEP) applications. We will motivate the need of EATDD in this domain and argue that state of the art solutions do not address this topic or have substantial weaknesses. We show the design approach of our testing system including a vendor independent testing syntax. We also state relevant challenges for testing CEP applications and discuss implementation details of our solution. On the basis of a real world scenario we demonstrate first practical experiences of our solution. QCEP-TS is available as open source project at http://sourceforge.net/p/qcep-ts. QCEP (Quality Assurance of Complex Event Processing) is a collaboration project of the Munich University of Applied Sciences, the Technical University of Dresden and the UniCredit Business Integrated Solutions S.C.p.A.
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Papers by Peter Mandl