Echocardiography in myocardial infarction : aspects on diastolic function and evaluation by cardiovascular magnetic resonance imaging

Background Echocardiography is routinely used to evaluate patients with known or suspected myocardial infarction (MI). Cardiovascular magnetic resonance imaging (CMR) provides the ability to quantify myocardial infarction size (IS), and to establish an underlying diagnosis in MI cases with nonobstructive coronary arteries (MINOCA). While echocardiography provides valuable information regarding cardiac function, the relationships between how pathology is manifested on CMR, and the information gleaned from echocardiography are not fully explored. The focus of this thesis was 1) to assess diastolic function and mechanics in MI, and 2) to assess the ability of echocardiography to identify patients needing further evaluation by CMR in MINOCA. Methods and results In Study I, a software application was developed for the purpose of facilitating the analysis of diastolic function using the parameterized diastolic filling (PDF) method. Inter- and intraobserver variability was studied using patients from Study III and Study IV. The software was successfully developed and made publicly available at www.echoewaves.org, and inter- and intraobserver reliability was good or excellent for most PDF measures (intraclass correlation coefficient 0.80-0.99). In Study II, an available clinical database of patients undergoing resting and stress echocardiography was used to identify a cohort of patients with normal echocardiographic findings. PDF analysis was performed in 138 patients for the establishment of normal reference values for the method, and presented as sex-specific 95% reference intervals. In Study III, a pre-planned substudy of the RECOND trial, the association between myocardial infarction size (IS) and parameters of diastolic function, and whether the peri-infarction edema of the myocardium at risk (MaR) influenced these relationships was investigated. Weak associations were found between IS and deceleration time (R² = 0.24, p < 0.001), left atrial volume index (R² = 0.13, p = 0.01), and the PDF stiffness parameter k (R² = 0.21, p < 0.001). The only parameter influenced by the addition of MaR was e′ (increase in adjusted R² = 0.08, p = 0.02). The PDF damping parameter c was the only parameter associated with final IS at 6 months follow-up (R² = 0.22, p = 0.001). In Study IV, a pre-planned substudy of the SMINC2 study, the value of normal vs pathological echocardiography, as well as the blood biomarkers hs-TnT and NT-pro-BNP, for selecting patients presenting with MINOCA for further evaluation with CMR was investigated. Pathological echocardiography identified patients with a CMR diagnosis with sensitivity 77%, specificity 38%, positive predictive value 82%, and negative predictive value 30%. At low levels of hs-TnT and NT-pro-BNP, the probability of obtaining a diagnosis by CMR was still substantial (> 25%). Conclusions and summary In summary, a freely available and reliable software application for the application of the PDF method was developed (Study I), and normal reference limits were provided, for use in further clinical research (Study II). IS as measured by CMR does not seem to be a major determinant of diastolic dysfunction after MI, and other factors are likely to be more important (Study III). CMR is a valuable diagnostic tool for the evaluation of patients with MINOCA, even when echocardiographic examinations are normal, and levels of hs-TnT and NT-pro-BNP are low (Study IV)

Kungsbackafjorden (Västerhavet) 2011

Totalt fångades 22 arter av fisk och sju arter av kräftdjur under provfisket i Kungsbackafjorden i augusti 2011. De vanligaste fiskarterna i fångsten var ål, skärsnultra och stensnultra. Strandkrabban var den vanligaste kräftdjursarten i fångsten. • Antalet arter i fångsten och den totala medelfångsten av fisk i Kungsbackafjorden skiljer sig inte nämnvärt från fångster i övriga områden längs med västkusten som provfiskades med samma metodik under 2011. • Medelfångsten av rovfisk i Kungsbackafjorden är något lägre än i jämförda områden. Detta beror främst på lägre fångster av torskfiskar (torsk, vitling och gråsej) vilket kan vara en effekt av förekomsten av sötare vatten, där torskfiskarna inte trivs, i delar av fjorden. Fångsten av rovfisk är dock överlag låg i samtliga områden. • Medelfångsten av mesopredatorer i Kungsbackafjorden skiljer sig inte mot jämförda områden. De vanligaste mesopredatorerna i Kungsbackafjorden är skärsnultra, stensnultra, skrubbskädda, svart smörbult och tånglake. • Stora fiskar (≥ 30 cm) är, bortsett från ål (gulål), ovanliga i fångsterna från samtliga provfiskade områden 2011. Medelfångsten av större torskar och skrubbskäddor skiljer sig heller inte nämnvärt i jämförelse med övriga områden. • Fisksamhället i Kungsbackafjorden är mångfasetterat, dels på grund av att arternas förekomst skiljer sig i djupled beroende på varmare och kallare vatten men även på grund av att det finns en tydlig gradient i salthalt från inre till yttre delarna av fjorden som påverkar artsammansättningen. • Torskfiskarna (torsk, sej, vitling och lyrtorsk) förekommer i högre antal i fjordens yttre och djupare delar där salthalten är högre medan de limniska arterna (abborre, id, mört och löja) förekommer längre in i fjorden där salthalten är lägre. Förekomsten av skärsnultra och stensnultra, två arter med likartade livsstrategier, skiljer sig åt i fjorden med mer skärsnultra i de västra delarna av områdets yttre del medan stensnultran förkommer i större antal i den östra delen men också lite mer skyddat och längre in i fjorde

Different induction mechanisms of mRNA for inducible nitric oxide synthase in rat smooth muscle cells in culture and in aortic strips

AbstractThe expression of mRNA for the inducible form of nitric oxide synthase, (iNOS), was studied in rat aortic smooth muscle cells, (SMCs) in cell culture and in strips of rat aorta by reverse transcriptase coupled to the polymerase chain reaction. iNOS mRNA expression was weak in cultured SMCs when exposed to either interferon-γ (IFNγ) or lipopolysaccharide (LPS), but the combination LPS + IFNγ enhanced the expression. In aortic strips LPS alone induced a pronounced expression, with no further increase by IFNγ. Cycloheximide potentiated the expression of iNOS mRNA in SMCs in culture stimulated with LPS + IFNγ but attenuated the response in aortic strips.The results indicate different cellular signaling pathways for the induction of iNOS mRNA by LPS and/or IFNγ, in cultured SMCs and in rat aortic strips

Finnish new variant of Chlamydia trachomatis escaping detection in the Aptima Combo 2 assay also present in Orebro County, Sweden, May 2019

We identified the first two cases of the Finnish new variant of Chlamydia trachomatis (F-nvCT) beyond Finland in two clinical urogenital specimens in Orebro County, Sweden. These Aptima Combo 2 assay-negative specimens were Aptima Chlamydia trachomatis (CT) assay positive and had the characteristic C1515T mutation in the 23S rRNA gene. From 22 March to 31 May 2019, 1.3% (2/158) of the CT-positive cases in Orebro County were missed because of the F-nvCT. International awareness, investigations and actions are essential.Peer reviewe

Использование нетрадиционных методов лечения в дерматовенерологии

ВЕНЕРОЛОГИЯДЕРМАТОЛОГИЯМЕДИЦИНА ТРАДИЦИОННА

The risk of HCV RNA contamination in serology screening instruments with a fixed needle for sample transfer

AbstractBackgroundHepatitis C diagnostics involve antibody screening and confirmation of current infection by detection of HCV RNA positivity. In screening instruments with fixed pipetting needle, there is a risk of sample carry-over contamination.ObjectivesThe aim of this study was to evaluate the risk of such contamination in a proposed clinical setting.Study designIn the present study, known HCV RNA positive (n=149) and negative (n=149) samples were analysed by anti-HCV Abbott in an Architect instrument in an alternating fashion in order to test for contamination.ResultsIn subsequent retesting of the previously HCV RNA-negative samples, six samples (4%) were positive by the Cobas Taqman assay with a maximum level of 33IU/mL. The results show that there is a risk for transfer of HCV in the Architect instrument but they also show that the levels of HCV RNA observed are low.ConclusionsWe conclude that complementary HCV RNA testing on samples identified as anti-HCV positive by screening can be recommended because the complementary results are reliable in the majority of cases when either HCV RNA is negative or HCV RNA is positive with a level >1000IU/mL. In a minority of cases, with low HCV RNA after anti-HCV antibody screening, cross-contamination should be suspected and a new sample requested for HCV RNA testing. This strategy would reduce the need for obtaining a new sample from the vast majority of patients with a newly discovered HCV antibody positivity

Expressing the human proteome for affinity proteomics: optimising expression of soluble protein domains and in vivo biotinylation

The generation of affinity reagents to large numbers of human proteins depends on the ability to express the target proteins as high-quality antigens. The Structural Genomics Consortium (SGC) focuses on the production and structure determination of human proteins. In a 7-year period, the SGC has deposited crystal structures of >800 human protein domains, and has additionally expressed and purified a similar number of protein domains that have not yet been crystallised. The targets include a diversity of protein domains, with an attempt to provide high coverage of protein families. The family approach provides an excellent basis for characterising the selectivity of affinity reagents. We present a summary of the approaches used to generate purified human proteins or protein domains, a test case demonstrating the ability to rapidly generate new proteins, and an optimisation study on the modification of >70 proteins by biotinylation in vivo. These results provide a unique synergy between large-scale structural projects and the recent efforts to produce a wide coverage of affinity reagents to the human proteome

Sensitivity, specificity, inclusivity and exclusivity of the updated Aptima Combo 2 assay, which provides detection coverage of the new diagnostic-escapeChlamydia trachomatisvariants

Background Four new variants ofChlamydia trachomatis(nvCTs), detected in several countries, cause false-negative or equivocal results using the Aptima Combo 2 assay (AC2; Hologic). We evaluated the clinical sensitivity and specificity, as well as the analytical inclusivity and exclusivity of the updated AC2 for the detection of CT andNeisseria gonorrhoeae(NG) on the automated Panther system (Hologic). Methods We examined 1004 clinical AC2 samples and 225 analytical samples spiked with phenotypically and/or genetically diverse NG and CT strains, and other potentially cross-reacting microbial species. The clinical AC2 samples included CT wild type (WT)-positive (n = 488), all four described AC2 diagnostic-escape nvCTs (n = 170), NG-positive (n = 214), and CT/NG-negative (n = 202) specimens. Results All nvCT-positive samples (100%) and 486 (99.6%) of the CT WT-positive samples were positive in the updated AC2. All NG-positive, CT/NG-negative,Trichomonas vaginalis(TV)-positive, bacterial vaginosis-positive, andCandida-positive AC2 specimens gave correct results. The clinical sensitivity and specificity of the updated AC2 for CT detection was 99.7 and 100%, respectively, and for NG detection was 100% for both. Examining spiked samples, the analytical inclusivity and exclusivity were 100%, i.e., in clinically relevant concentrations of spiked microbe. Conclusions The updated AC2, including two CT targets and one NG target, showed a high sensitivity, specificity, inclusivity and exclusivity for the detection of CT WT, nvCTs, and NG. The updated AC2 on the fully automated Panther system offers a simple, rapid, high-throughput, sensitive, and specific diagnosis of CT and NG, which can easily be combined with detection ofMycoplasma genitaliumand TV.Peer reviewe

Sensitivity, specificity, inclusivity and exclusivity of the updated Aptima Combo 2 assay, which provides detection coverage of the new diagnostic-escapeChlamydia trachomatisvariants

Background Four new variants ofChlamydia trachomatis(nvCTs), detected in several countries, cause false-negative or equivocal results using the Aptima Combo 2 assay (AC2; Hologic). We evaluated the clinical sensitivity and specificity, as well as the analytical inclusivity and exclusivity of the updated AC2 for the detection of CT andNeisseria gonorrhoeae(NG) on the automated Panther system (Hologic). Methods We examined 1004 clinical AC2 samples and 225 analytical samples spiked with phenotypically and/or genetically diverse NG and CT strains, and other potentially cross-reacting microbial species. The clinical AC2 samples included CT wild type (WT)-positive (n = 488), all four described AC2 diagnostic-escape nvCTs (n = 170), NG-positive (n = 214), and CT/NG-negative (n = 202) specimens. Results All nvCT-positive samples (100%) and 486 (99.6%) of the CT WT-positive samples were positive in the updated AC2. All NG-positive, CT/NG-negative,Trichomonas vaginalis(TV)-positive, bacterial vaginosis-positive, andCandida-positive AC2 specimens gave correct results. The clinical sensitivity and specificity of the updated AC2 for CT detection was 99.7 and 100%, respectively, and for NG detection was 100% for both. Examining spiked samples, the analytical inclusivity and exclusivity were 100%, i.e., in clinically relevant concentrations of spiked microbe. Conclusions The updated AC2, including two CT targets and one NG target, showed a high sensitivity, specificity, inclusivity and exclusivity for the detection of CT WT, nvCTs, and NG. The updated AC2 on the fully automated Panther system offers a simple, rapid, high-throughput, sensitive, and specific diagnosis of CT and NG, which can easily be combined with detection ofMycoplasma genitaliumand TV.Peer reviewe