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Inversion of pre‐existing normal faults is a frequent phenomenon in orogenic belts. However, their impact on the evolution of the Cretaceous Eoalpine orogeny is poorly studied, despite the widespread presence of Triassic and Jurassic normal faults. Our study area is the SW part of the Transdanubian Range (TR), which represents the uppermost thick‐skinned nappe of the Eoalpine orogeny in the Alpine realm. The variable trend of Cretaceous contractional structures within the Transdanubian Range has been traditionally explained by poly‐phase shortening. However, based on the combined analyses of field observations and 3D seismic data, we found that the complex geometry of Cretaceous contractional structures can be explained rather by the oblique inversion of segmented Late Triassic grabens. In general, the SW part of the TR can be characterized by N‐S trending contractional structures. NW‐SE striking oblique ramps are nucleated above Late Triassic normal faults, whereas NE‐SW trending folds and thrust with limited strike‐parallel length evolved due to the inversion of pre‐existing breached relay ramps, which connected the segments of Late Triassic normal faults. We determined different types of oblique ramps, incuding normal faults, which suffered transpressional reactivation, oblique hanging wall breakthrough thrusts, oblique footwall short‐cut and hanging wall by‐pass thrusts. Only very steep normal faults, or those that strike at low angle to the regional E‐W shortening direction, were not reactivated. Key Points: The oblique ramps of the study area formed due to the oblique inversion of a rift related graben‐systemDuring inversion, those pre‐existing normal faults were reactivated, that enclosed a high angle to the direction of shorteningSpatial relationship of the inversion related obliqe ramps and the earlier normal faults led us to define four styles of oblique inversion [ABSTRACT FROM AUTHOR]

Summary: The Tie2 receptor is an important player in angiogenesis. The Tie2 mRNA and protein are abundantly expressed in the lungs and the associated pathway also has an important role in the development and function of the eye. Tie2 is encoded by the TEK gene in humans. Recently, variations in the TEK gene have been found associated with asthma. The objective of the present study was to investigate whether variations in the TEK gene influenced the susceptibility to pediatric asthma and/or associated phenotypes like GINA status, viral‐ or exercise‐induced asthma, allergic asthma, indoor, outdoor, inhalative allergies, IgE and eosonophil levels, allergic rhinitis and allergic conjunctivitis. Three single nucleotide polymorphisms (SNPs, rs3780315, rs581724 and rs7876024) in the TEK gene were genotyped in 1189 unrelated individuals, out of which 435 were asthmatic children and 754 healthy controls. Different types of asthma, allergies and co‐morbidities were defined in 320 patients. Among the fully phenotyped 320 asthmatic patients 178 (55.6%) also had allergic rhinitis and 100 (31.3%) had conjunctivitis. Among the rhinitis patients 98 (55.1%) also had conjunctivitis. Two patients had conjunctivitis without rhinitis. The genotyped SNPs showed no association with asthma. However, SNP rs581724 was significantly associated with allergic conjunctivitis in a recessive way (p=0.007; OR=2.3 (1.3‐4.4)) within the asthmatic population. The risk remained significant when the whole population (asthmatics and healthy controls) was included in the calculation (p = 0.003; OR = 2.1 (1.3‐3.6)). The minor allele of the rs581724 SNP which is associated with the increased risk to conjunctivitis is also associated with reduced Tie2 expression. There was a significant association between SNP rs581724 and the occurrence of allergic conjunctivitis in asthmatic children. If additional studies can confirm the role of the Tie2 pathway in allergic conjunctivitis, it can be a potential novel therapeutic target in the disease. [ABSTRACT FROM AUTHOR]

Contents The aim of the study was to investigate the effect of Bovine Herpesvirus 4 (Bo HV-4) and Histophilus (H.) somni on fertility rate of cows in a Hungarian Holstein-Friesian dairy herd with purulent vaginal discharge (PVD). Non-pregnant cows (n = 188) with mature corpus luteum were treated with cloprostenol and 3 days later if they did not show oestrus, were examined by rectal palpation. Animals showing PVD (n = 60/31.9%/) and 14 controls with normal vaginal discharge (Score 0) were randomly selected and further examined by ultrasonography and blood samples were collected for detecting Bo HV-4 DNA and transcervical guarded swabs were collected from the uterus for bacteriological examination. Although the majority of the examined animals were infected with Bo HV-4 and H. somni including the control animals as well, in group of animals with PVD score 3, fewer animals became pregnant and the duration between the first treatment to pregnancy was significantly extended. Based on these clinical and comparative data, our results confirm that these two microorganisms together may impair important reproductive parameters which may cause large economic losses to dairy farms. [ABSTRACT FROM AUTHOR]

Background: About 240 million patients undergo surgery every year, worldwide. Roughly 50% of these patients report clinically significant pain. Numerous barriers impede provision of adequate management. Lack of evidence about appropriateness and effectiveness of interventions is one. A registry can provide such information, eventually facilitating better management. This paper reports the development and feasibility of PAIN OUT, the first international acute pain registry, established with funds from the European Commission, and presents preliminary analysis to illustrate the nature of investigations that registry data make possible. Methods: On the first postoperative day, 6347 adult patients undergoing orthopaedic or general surgery, in 11 medical centres in Europe and Israel, provided Patient Reported Outcomes (PROs) using a validated questionnaire. Clinical data were abstracted from the patient's chart. Results: Feasibility worked well. Over a period of 1 year, surveyors accrued targeted data sets and entered them into an online browser. Collaborators could receive online feedback comparing their findings about PROs against anonymized findings from other centres. Missing data for the majority of variables were low. Despite considerable variability between institutions, a large number of patients were treated according to the generic, evidence ‐ based recommendations we assessed. However, this was not sufficient to result in acceptable outcomes for the majority of patients. Conclusion: The initial development of PAIN OUT has been achieved. From 2013, it continues as a not ‐ for ‐ profit academic project, open to clinicians and researchers worldwide. The International Association for Study of Pain and PAIN OUT will work together to maintain, disseminate and develop the registry. [ABSTRACT FROM AUTHOR]

Post-operative pain exacts a high toll from patients, families, healthcare professionals and healthcare systems worldwide. PAIN-OUT is a research project funded by the European Union's 7th Framework Program designed to develop effective, evidence-based approaches to improve pain management after surgery, including creating a registry for feedback, benchmarking and decision support. In preparation for PAIN-OUT, we conducted a pilot study to evaluate the feasibility of international data collection with feedback to participating sites. Adult orthopaedic or general surgery patients consented to participate between May and October 2008 at 14 collaborating hospitals in 13 countries. Project staff collected patient-reported outcomes and process data from 688 patients and entered the data into an online database. Project staff in 10 institutions met the enrolment criteria of collecting data from at least 50 patients. The completeness and quality of the data, as assessed by rate of missing data, were acceptable; only 2% of process data and 0.06% of patient-reported outcome data were missing. Participating institutions received access to select items as Web-based feedback comparing their outcomes to those of the other sites, presented anonymously. We achieved proof of concept because staff and patients in all 14 sites cooperated well despite marked differences in cultures, nationalities and languages, and a central database management team was able to provide valuable feedback to all. [ABSTRACT FROM AUTHOR]

Thirteen Francisella tularensis strains were isolated from 22 seropositive brown hares ( Lepus europaeus) originating from different parts of Hungary, and further two from a patas monkey ( Erythrocebus patas) and vervet monkey ( Chlorocebus aethiops). The isolates were identified as F. tularensis ssp. holarctica on the basis of culture, morphological and biochemical characteristics. The identification was verified by polymerase chain reaction and the sequencing of the partial 16S rRNA gene. Utilization of carbon sources of the 15 F. tularensis strains was characterized with the Biolog system. The system was able to identify the strains already after 4 h of incubation, not only after the standard 24 h. After the analysis and comparison of the metabolic profiles of our strains with the Biolog database, it was concluded that not all carbon sources indicated in the database were utilized by our isolates. The Biolog software fails to distinguish the highly virulent F. tularensis ssp. tularensis and the moderately virulent F. tularensis ssp. holarctica but the Biolog microplates can be manually read to differentiate the two subspecies based on glycerol source utilization. As all the studied strains were unable to use glycerol, they could be identified as F. tularensis ssp. holarctica. The dendrogram based on the metabolic relationship of the strains shows that the isolates are very similar to each other, which correlates with the conservative genetic character of F. tularensis ssp. holarctica. [ABSTRACT FROM AUTHOR]

Background and purpose:High-affinity, subtype-selective antagonists of the neurosteroid binding sites of GABAA receptors are not available. We have characterized an allopregnanolone derivative as an antagonist of cerebellar GABAA receptors with nanomolar affinity.Experimental approach:Receptor binding and electrophysiological methods were used for the allosteric modulation of cerebellar GABAA receptors by an allopregnanolone derivative, (20R)-17β-(1-hydroxy-2,3-butadienyl)-5α-androstane-3α-ol (HBAO). GABAA receptors of rat cerebellar membranes were labelled with the chloride channel blocker [3H]ethynylbicycloorthobenzoate (EBOB). The ionophore function of GABAA receptors was studied by whole-cell patch clamp electrophysiology in cultured rat cerebellar granule and cortical cells.Key results:Partial displacement of cerebellar [3H]EBOB binding by nanomolar HBAO was attenuated by 0.1 mM furosemide, an antagonist of α6 and β2-3 subunit-containing GABAA receptors. Displacement curves of HBAO were reshaped by 30 nM GABA and shifted to the right. However, the micromolar potency of full displacement by allopregnanolone was not affected by 0.1 mM furosemide or 30 nM GABA. The nanomolar, but not the micromolar phase of displacement of [3H]EBOB binding by GABA was attenuated by 100 nM HBAO. Submicromolar HBAO did not affect [3H]EBOB binding to cortical and hippocampal GABAA receptors. HBAO up to 1 μM did not affect chloride currents elicited by 0.3-10 μM GABA, while it abolished potentiation by 1 μM allopregnanolone with nanomolar potency in cerebellar but not in cortical cells. Furosemide attenuated cerebellar inhibition by 100 nM HBAO.Conclusions and implications:HBAO is a selective antagonist of allopregnanolone, a major endogenous positive modulator via neurosteroid sites of cerebellar (probably α6β2–3δ) GABAA receptors.British Journal of Pharmacology (2007) 151, 1078–1086; doi:10.1038/sj.bjp.0707316; published online 11 June 2007 [ABSTRACT FROM AUTHOR]

Background Removal of skin lesions is one of the most common surgical procedures, with the number increasing progressively since the 1980s. Objective We tried to evaluate the satisfaction level of patients after removal of skin lesions and to identify the factors influencing it. Study design The study group consisted of 138 patients who had skin lesions removed by shaving or primary excision and closure. They were evaluated 1 year after the procedure. Two questionnaires were completed independently by the patient and the surgeon. Results The main indication for the procedure was suspicion of malignancy, functional disturbance, or aesthetic reason. The satisfaction level (general and specific areas) for patients who had a malignant tumour removed was similar to those who had a benign tumour removed. Females were less satisfied than males ( P = 0.05). Younger people were less satisfied with the aesthetic results ( P = 0.007). Patients who had at least one significant side-effect were less satisfied than those who did not mention any side-effects ( P = 0.038). The higher the level of patient satisfaction, the higher the level of surgeon satisfaction ( P = 0.012). Conclusion Skin lesions removal, although considered to be a minor procedure, leaves scars that sometimes disturb the patient. According to our study, the most prevalent population for dissatisfaction is females and young males. [ABSTRACT FROM AUTHOR]

Field examples of fault-related folds were observed in the south-western margin of the Sirt basin, south-central Libya. Single or paired (conjugate) monoclines, drape synclines, special drag faults can be put in a geometric and evolutionary model, which describes the propagation of basement faults to overlying sediments. At the first stage of evolution the propagating normal or oblique-slip faults show segmentation along-dip direction. Fault segments are separated by continuous, moderately to strongly bended horizons, which show different degrees of diagenesis than surrounding intervals. Fault-related folding and faulting was coeval with lithification of certain carbonate levels. Their gradual cementation increased the rigidity of layers promoting discrete faulting and breaching of fault-related folds. However, folding can be maintained up to the extent when layer dip approaches the dip of the propagating fault zone. This type of deformation can be characteristic for sequences consisted of lithified carbonates sandwiched between thicker marl/shale intervals.Terra Nova, 17, 121–128, 2005 [ABSTRACT FROM AUTHOR]

Examines the serotypes of pasteurella haemolytica and pasteurella trehalosi isolated from farm animals in Hungary. Results of serotyping; Percentage of caprine isolates; Basis of chemical tests.

Eubacterium suis was isolated from the preputium of seven out of 16 mature boars on two farms and from the urinary bladder of one out of five sows originating from a third herd. The morphological and biochemical characteristics of the isolated strains were identical to that of the reference strain of E suis ATTC 33144. Three out of four strains isolated from Farm A were successfully subcultured aerobically, and then anaerobically again. E. suis together with Proteus mirabilis was isolated from cystitis of a sow 4 days after artificial insemination. These are the first strains of E. suis isolated in Hungary. [ABSTRACT FROM AUTHOR]

A total of seven Bacteroides ureolyticus strains were isolated from the cervix and the clitoral fossa of mares with vaginal discharge. No other bacteria capable of causing metritis or vaginitis were isolated from the samples. The isolated strains resembled Taylorella equigenitalis. Both species are catalase, oxidase and alkaline phosphatase positive, but, in addition to these characteristics, B. ureolyticus strains produced urease and they could not tolerate 10% O2. They also failed to be agglutinated in a hyperimmune serum raised against T. equigenitalis; however, B. ureolyticus and T. equigenitalis were agglutinated in the slide agglutination test in a serum produced against one of the B. ureolyticus isolates. Further investigations are needed to clarify the pathologic role of B. ureolyticus in genital infections of mares and other animals. [ABSTRACT FROM AUTHOR]

Of 38 aborted ovine fetuses from 23 sheep flocks 29 C. fetus subsp. fetus and 22 C. jejuni were isolated and examined biochemically and serologically for heat-stable antigens. Serologic examinations were carried out by passive haemagglutination test. In case of C. fetus subsp. fetus strains alkaline antigen extraction was used. Antisera to two serogroups of C. fetus and to Penner serotype reference strains 1 to 60 were produced in rabbits. Abortion was caused in 18 (78.3%) flocks by C. fetus subsp. fetus and in 5 (21.7%) flocks by C. jejuni. Six C. fetus subsp. fetus strains grew well at both 43 and 25 °C. With one exception all C. fetus subsp. fetus were resistant, wheras all 29 C. fetus subsp. venerealis strains were sensitive to 30 μg/ml cefoxitin and cefamandole. These two cephalosporins can be used to differentiate the two subspecies of C. fetus. Passive haemagglutination test using alkaline antigen extraction is a proper method for the examination of heat-stable antigens of both C. fetus subspecies. Out of 24 C. fetus subsp. fetus strains 13 belonged to serogroup A(01), and 11 to serogroup B(02). C. jejuni strains examined belonged to Penner serogroup 1 (6 strains), to serogroup 5 (4 strains) and to serogroup 8 (4 strains). Zusammenfassung Aus 38 abortierten Schaffeten von 23 Schafherden wurden 29 C. fetus subsp. fetus und 22 C. jejuni isoliert und biochemisch sowie serologisch auf hitzestabile Antigene untersucht. Serologische Untersuchungen wurden mit Hilfe der passiven Haemagglutination durchgeführt. Bei C. fetus subsp. fetus wurde die alkalische Antigenextraktion angewendet. Antiseren gegen die beiden Serogruppen von C. fetus und gegen die 'Penner'-Serotyp-Referenzstämme 1 bis 60 wurden in Kaninchen hergestellt. In 18 Herden (78,3 %) wurden die Aborte durch C. fetus subsp. fetus und in 5 Herden (21,7%) durch C. jejuni verursacht. Sechs Stämme von C. fetus subsp. fetus wuchsen gut bei Temperaturen von 43 °C und 25 °C. Mit einer Ausnahme waren alle C. fetus subsp. fetus-Stämme resistent, wogegen alle 29 C. fetus subsp. venerealis-Stämme empfindlich gegen 30 μg/ml Cefoxitin und Cefamandole waren. Diese beiden Cephalosporine können zur Differenzierung der beiden Subspezies von C. fetus herangezogen werden. Der passive Hämagglutinationstest, ausgeführt mit alkalischem Antigenextrakt, ist eine geeignete Methode für die Untersuchung von hitzestabilen Antigenen der beiden C. fetus-Subspezies. Von den 24 C. fetus subsp. fetus-Stämmen gehörten 13 zur Serogruppe A(01) und 11 zur Serogruppe B(02). Die untersuchten C. jejuni-Stämme gehörten zur 'Penner'-Serogruppe 1 (6 Stämme), zur Serogruppe 5 (4 Stämme) und zur Serogruppe 8 (4 Stämme). [ABSTRACT FROM AUTHOR]

A total of 186 campylobacter strains from aborted calf and sheep fetuses, from scouring dogs, rabbits and man, and from retailed poultry were isolated and examined biochemically and serologically for heat stable antigens. Immune sera were produced in rabbits against Penner reference strains from 1 to 60, and against two field isolates. Out of 186 biochemically tested strains 179 (96.2 %) proved C. jejuni and only 6 (3.2 %) C. coli. One strain has been identified as C. laridis. In cattle and sheep 3.2 and 21.7% respectively of all campylobacter abortions were due to C. jejuni infection. The same agent caused 12.7 % of diarrhoea of dogs. The campylobacter infection rate of freshly slaughtered and dressed chicken varied between 25 and 64.3%. Out of the serologically examined 140 C. jejuni strains 118 (84.3%) could be assigned to 16 Penner serogroups and 13 (9.3%) to 2 further serogroups. Serogroups 8 (31.4%), 1 (19.3%) and 2 (12.1 %) occurred most frequently. The human isolates represented the widest serotype distribution, as 32 tested strains belonged to 12 serogroups. All those serogroups which caused abortion or diarrhoea in animals or were isolated from poultry carcases were isolated also from man with diarrhoea, but some serogroups were found only in man. [ABSTRACT FROM AUTHOR]

The biochemical properties of and haemagglutination by 23 Neisseria ovis strains isolated from the conjunctiva of sheep, both affected with keratoconjunctivitis and normal were examined; 48 N. ovis strains and 19 Moraxella bovis strains, all from cattle, were also tested. Four N. ovis and one M. bovis strains were investigated also by electron microscopy. N. ovis strains from sheep and cattle revealed similar morphological and biochemical features, but ovine strains in contrast to bovine ones agglutinated red blood cells of chicken, but not those of man, cattle, sheep, horse, rabbit and guinea pig. None of M. bovis strains revealed any haemagglutinating activity. Haemagglutinating N. ovis strains grew in R type colonies. The haemagglutination proved mannose resistant and was inactivated by heating the bacteria to at least 60 °C for 30 min. Haemagglutination by N. ovis strains isolated from several flocks of sheep was inhibited by an immune serum produced in rabbits against one of the strains. Electron microscopy did not reveal any fimbriae (pili) on the surface of haemagglutinating N. ovis bacteria. Zusammenfassung Es wurden die biochemischen Eigenschaften von und die Haemagglutination durch 23 Neisseria ovis-Stämme, die aus der Conjunctiva von gesunden und mit Keratoconjunctivitis befallenen Schafen isoliert wurden, ferner von 48 N. ovis-Stämmen von Rindern und von 19 Moraxella bovis-Stämmen getestet. Vier N. ovis-Stämme und ein M. bovis-Stamm wurden auch elektronenmikroskopisch untersucht. N. ovis-Stämme von Schafen und Rindern zeigten gleiche morphologische und biochemische Merkmale, aber ovine Stämme agglutinierten im Gegensatz zu den bovinen Stämmen rote Blutkörperchen von Hühnern, aber nicht jene von Mensch, Rind, Schaf, Pferd, Kaninchen und Meerschweinchen. Keiner der M. bovis-Stämme zeigte irgendeine haemagglutinatorische Aktivität. Haemagglutinierende N. ovis-Stämme wuchsen in R-Form-Kolonien. Die Haemagglutination erwies sich als mannoseresistent und wurde durch Erhitzung der Bakterien auf mindestens 60°C für 30 Minuten inaktiviert. Die Haemagglutination durch N. ovis-Stämme, isoliert aus verschiedenen Schafherden, wurde inhibiert durch ein Immunserum, das im Kaninchen gegen einen der Stämme hergestellt worden war. Die Elektronenmikroskopie zeigte keinerlei Fimbrien (Pili) auf der Oberfläche der haemagglutinierenden N. ovis-Bakterien. [ABSTRACT FROM AUTHOR]

Eighteen strains of Actinobacillus seminis isolated from ovine semen samples and epididymitis were characterized according to their cultural and biochemical behaviour. The semen samples were collected from young, unmated and mature breeding rams suffering from epididymitis or subclinical genital infection. All A. seminis strains were non-motile, non spore-forming, uncapsulated, Gram-negative pleomorphic rods, approximately 1-8 μm × 0.8-1 μm. On bovine blood agar they formed low convex, greyish-white, non-adherent and non-haemolytic colonies, which grew under aerobic conditions, but more luxuriantly when cultures were incubated in an atmosphere containing 10% CO2 at 37°C. All strains were catalase, oxidase, nitrate and ornithine decarboxylase positive, but indole, urease, phosphatase and beta-galactosidase (ONPG) negative. They were fermentative in the O/F test and usually produced acid within 1 to 3 days from glucose, arabinose, fructose, maltose and xylose, but not from lactose, mannose and sucrose. In the agar gel diffusion test, antigenic differences were demonstrated among the isolates. On the basis of the cultural, morphological and biochemical characteristics, A. seminis can be differentiated from other Gram-negative bacteria (e.g. Brucella ovis, Histophilus ovis etc.) involved in genital infections in rams. [ABSTRACT FROM AUTHOR]

From the genital organs of four, approximately 8-10 months old rams slaughtered because of severe bi- or unilateral, suppurative epididymo-orchitis, fastidious Gram-negative pleomorphic bacteria were isolated. The organism is non-motile, non-sporeforming and non-haemolytic. The four isolates grew only in an atmosphere containing 10 % CO2 in media enriched with blood, serum or meat extracts. The strains were catalase-negative, oxidase-positive, nitrate-positive and produced indole from tryptrophan. Urea was not decomposed and hydrogen sulphide was not produced. They were fermentative in the O/F test and produced acid from fructose, glucose, maltose, mannite, sorbitol and trehalose within 3 to 7 days. Based upon their properties, the organism isolated from the rams was identified as Histophilus ovis (Roberts, 1956). The morphological, cultural and biochemical characteristics of H. ovis strains were identical with those of Haemophilus somnus strains isolated from calves in Hungary. However, using the tube agglutination test antigenic differences were demonstrated between H. ovis and Haemophilus somnus strains. Zusammenfassung Ovine suppurative Epididymo-orchitis verursacht durch Histophilus ovis Aus den Genitalorganen von vier etwa 8-10 Monate alten Schafböcken, die wegen einer schweren ein- oder doppelseitigen Epididymo-orchitis geschlachtet wurden, konnten anspruchsvolle, gramnegative, pleomorphe Bakterien isoliert werden. Der Mikroorganismus ist unbeweglich, nicht sporenbildend und nicht hämolysierend. Die 4 Isolate wuchsen nur in einer 10%igen CO2-Atmo-sphäre im Medium angereichert mit Blut, Serum oder Fleischextrakt. Die Stämme waren Katalase-negativ, Oxidase-positiv, Nitrat-positiv und produzierten Indol aus Tryptophan, Harnsaft wurde nicht gespalten und H2S wurde nicht gebildet. Sie waren fermentativ im O/F-Test und spalteten unter Säurebildung Fruktose, Glukose, Maltose, Mannit, Sorbit und Trehalose innerhalb von 3-7 Tagen (Tab. 1). Aufgrund ihrer Eigenschaften wurden die aus Schafböcken isolierten Bakterien als Histophilus ovis (Roberts, 1956) identifiziert. Die morphologischen, kulturellen und biochemischen Charakteristika der H. ovis-Stämme waren identisch mit denen von H. sommnis-Stämmen, die aus Kälbern in Ungarn isoliert wurden. In der Serumlangsamagglutination konnten jedoch antigene Unterschiede zwischen H. ovis und H. somnis demonstriert werden. [ABSTRACT FROM AUTHOR]

Rationale, Aims and Objectives: Management of post-operative pain is unsatisfactory worldwide. An estimated 240 million patients undergo surgery each year. Forty to 60% of these patients report clinically significant pain. Discrepancy exists between availability of evidence-based medicine (EBM)-derived knowledge about management of perioperative pain and increased implementation of related practices versus lack of improvement in patient-reported outcomes (PROs). We aimed to assist health care providers to optimize perioperative pain management by developing and validating a medical registry that measures variability in care, identifies best pain management practices and assists clinicians in decision making., Methods: PAIN OUT was established from 2009 to 2012 with funding from the European Commission. It now continues as a self-sustaining, not-for-profit project, targeting health care professionals caring for patients undergoing surgery., Results: The growing registry includes data from 40 898 patients, 60 hospitals and 17 countries. Collaborators upload data (demographics, clinical, PROs) from patients undergoing surgery in their hospital/ward into an Internet-based portal. Two modules make use of the data: (1) online, immediate feedback and benchmarking compares PROs across sites while offline analysis permits in-depth analysis; and (2) the case-based clinical decision support system offers practice-based treatment recommendations for individual patients; it is available now as a prototype. The Electronic Knowledge Library provides succinct summaries on perioperative pain management, supporting knowledge transfer and application of EBM., Conclusion: PAIN OUT, a large, growing international registry, allows use of 'real-life' data related to management of perioperative pain. Ultimately, comparative analysis through audit, feedback and benchmarking will improve quality of care., (© 2014 John Wiley & Sons, Ltd.)

Objective: Endothelial nitric oxide synthase (eNOS), which produces NO, plays an important role in the endothelial function under a wide range of physiological conditions. eNOS exon 7 polymorphism (Glu298Asp, G894T) has been considered to influence the risk of coronary artery disease. Alone, however, it has not been shown to be a genetic risk factor for ischaemic stroke. With the assumption of additive interactions, we examined whether the eNOS G894T or eNOS 894TT genotypes in combination with the methylenetetrahydrofolate reductase 677TT (MTHFR 677TT) or angiotensin-converting enzyme (ACE) D/D genotype could contribute to acute ischaemic stroke., Material and Methods: The data on 407 consecutive patients with acute ischaemic stroke who had never suffered a previous stroke event were analysed. As a control group, 295 stroke and neuroimaging alteration-free Caucasian subjects were examined. With the use of the PCR technique, the eNOS G894T, eNOS 894TT, MTHFR 677TT and ACE D/D mutations, as unfavourable common genotypes were determined in the participants. Logistic regression models were used to evaluate the roles of the genotypes and their combinations in the development of ischaemic stroke., Results: The MTHFR C677TT genotype combined with the eNOS G894T or eNOS 894TT genotypes occurred significantly more frequently in the subjects with ischaemic stroke (7.1%; P < 0.025) than in the control group (3.1%). The co-occurrence of the ACE D/D genotype and eNOS G894T or eNOS 894TT was calculated to be more frequent in the ischaemic stroke group (20.9%, P < 0.0001) than in the control group (5.4%)., Conclusion: The eNOS G894T or eNOS 894TT genotypes in combination with the MTHFR 677TT or ACE D/D genotype increases the risk of ischaemic stroke., (Blackwell Munksgaard 2004)

Objective: Ischaemic demyelination of the white matter of the brain is a frequent clinical entity. In the neuroimaging terms, it is referred to as leukoaraiosis. We earlier found that the co-occurrence of the homozygous methylenetetrahydrofolate reductase (MTHFR) 677TT and angiotensin-converting enzyme D/D (ACE D/D) genotypes yielded a highly significant moderate risk of leukoaraiosis. On the assumption of further genetic interactions, we have now investigated whether the different apolipoprotein E (APO E) genotypes, in pairwise combinations with the MTHFR 677TT or ACE D/D mutation, could lead to an increased risk of leukoaraiosis., Material and Methods: We analysed the occurrence of the APO E genotypes in pairwise combinations with the MTHFR 677TT or ACE D/D mutation in 315 consecutive Caucasian patients with leukoaraiosis. A total of 646 neuroimaging-free subjects acted as a control group., Results: The APO E 2/2 and 2/3 or APO E 4/4 and 4/3 genotypes in combination with the MTHFR 677TT or ACE D/D mutation exhibited independent genetic risks of leukoaraiosis., Conclusion: The interactions of certain unfavourable genetic mutations can contribute to the evolution of leukoaraiosis.

Objectives: Leukoaraiosis, a relatively frequent neuroimaging entity, is presumed to be primarily a vascular problem. However, it can be explained only in part by vascular risk factors. With the assumption of genetic susceptibility, the roles of common genetic polymorphisms and mutations in leukoaraiosis were examined in this study., Material and Methods: A detailed clinical scrutiny of 843 Hungarian neurological patients with mild cognitive-like complaints revealed 229 subjects with leukoaraiosis that was probably vascular in origin: 143 with leukoaraiosis alone (group 1), and 86 with leukoaraiosis plus cerebral infarction (group 2). In all 229 patients, the methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutation and angiotensin-converting enzyme (ACE I/D) polymorphism were examined by means of the PCR technique. The prevalences of the different genotypes for the examined mutations in the 2 groups were analysed in comparison with the data on 362 neuroimaging alteration-free subjects as controls., Results: The ACE D/D genotype (38.37%, P<0.0005; OR 2.46, 95% CI, 1.49-4.08) and ACE D allele (61%; P<0.001) were more frequent in group 2 than in the control group (20.17%; 47%). Neither the homozygous nor the heterozygous MTHFR C677T mutation alone was found to be a risk factor for leukoaraiosis. The homozygous MTHFR C677T mutation combined with the ACE D/D genotype was significantly more frequent in group 1 (11.89%, P<0.0005; OR 4.75, 95% CI, 2.12-10.65), in group 2 (12.79%, P<0.0005; OR 5.16, 95% CI, 2.12-12.6) and in combined group 1+2 (12.23%, P<0.0005; OR 4.9, 95% CI, 2.33-10.3) than in the control group (2.76%)., Conclusion: These data indicate that the contributions of the ACE D/D genotype and the homozygous MTHFR C677T mutation to leukoaraiosis should be taken into consideration not as major, but as additive factors. These findings draw attention to the fact that genetic polymorphisms that alone are insignificant can be risk factors for leukoaraiosis if they cluster in the same subjects.

Objectives: The aetiological role of common genetic mutations was analysed in a subgroup of stroke patients., Material and Methods: A total of 406 patients were examined because of ischaemic stroke. After a detailed clinical scrutiny, 5 were found who did not exhibit any of the classical clinical risk factors. In this clinically homogeneous subgroup of stroke patients, the prothrombin A20210G, Hong Kong, Cambridge and methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations, angiotensin-converting enzyme polymorphism (ACE polymorphism) and apolipoprotein E (APO E) genotype were examined., Results: In all 5 patients, the same type of clustering of three mutations was manifested. A heterozygous Leiden V mutation was observed in all 5 subjects, while a heterozygous MTHFR C677T mutation and an I/D genotype for ACE polymorphism were detected in 4 of them, and a homozygous D/D genotype and a homozygous MTHFR C677T mutation in 1. This type of clustering of the mutations was not observed in the remaining 401 stroke patients., Conclusion: These results suggest that the Leiden mutation might possibly be an aetiological factor for stroke in a rare subgroup of patients who do not display any of the classical risk factors. The roles of ACE D polymorphism and the MTHFR C677T mutation in stroke, should also be taken into consideration in this subgroup of stroke patients. These unfavourable genetic factors might be aetiological factors if they are clustered together in a stroke patient not presenting any of the standard clinical risk factors.