Pre-procedural image-guided versus non-image-guided ventricular tachycardia ablation-a review.

BACKGROUND: Magnetic resonance imaging and computed tomography in patients with ventricular tachycardia (VT) after myocardial infarction (MI) helps to delineate scar from healthy tissue. Image-guided VT ablation has not yet been studied on a large scale. OBJECTIVE: The aim of the meta-analysis was to compare the long-term outcome of image-guided VT ablation with a conventional approach for VT after MI. METHODS: Eight electronic bibliographic databases were searched to identify all relevant studies from 2012 until 2018. The search for scientific literature was performed for studies that described the outcome of VT ablation in patients with an ischaemic substrate. The outcome of image-guided ablation was compared with the outcome of conventional ablations. RESULTS: Of the 2990 citations reviewed for eligibility, 38 articles-enrolling a total of 7748 patients-were included into the meta-analysis. Five articles included patients with image-guided ablation. VT-free survival was 82% [74-90] in the image-guided VT ablation versus 59% [54-64] in the conventional ablation group (p < 0.001) during a mean follow-up of 35 months. Overall survival was 94% [90-98] in the image-guided versus 82% [76-88] in the conventional VT ablation group (p < 0.001). CONCLUSIONS: Image-guided VT ablation in ischaemic VT was associated with a significant benefit in VT-free and overall survival as compared with conventional VT ablation. Visualising myocardial scar facilitates substrate-guided ablation procedures, pre-procedurally and by integrating imaging during the procedure, and may consequently improve long-term outcome.

Scintillator screen development for fast neutron radiography and tomography and its application at the beamline of the 10 MW BNC research reactor.

Simple and inexpensive ZnS-based fast neutron imaging screens have been developed and their performance has been tested and compared to a commercially available one using the RAD beamline of the 10 MW research reactor of the Budapest Neutron Centre (BNC), Hungary. ZnS(Ag) and ZnS(Cu) powders have been mixed with optical epoxy, deaerated and casted into sheet form using an aluminum frame. The ZnS concentration and the screen thickness have been optimised using sample screen pieces. The in-house screens have been tested in camera-based neutron imaging detectors in a reactor beamline and compared with a commercially available polypropylene/ZnS(Cu) fast neutron imaging screen and with a BC400 plastic scintillator slab screen. It has been found that the in-house screen produces only about 60% of light intensity of the commercial polypropylene/ZnS screen, which is mainly due to the lower hydrogen density of the optical epoxy compared to polypropylene by the same amount. The BC400 performs inferior compared to any ZnS-based scintillator tested here. Fast neutron tomography has been performed with both the commercial and the in-house screens on the reactor beamline. A spatial resolution of around 1.6 mm has been achieved. Typically 10-15 min exposures were needed to obtain good quality radiographic images, whereas several hours of acquisition were needed to obtain the full tomographic set images. High quality imaging results have been obtained on large (150 mm in diameter) and dense objects (hydraulic couplings) proving the feasibility and utility of fast neutron imaging for such samples.

Fast neutron radiography and tomography at a 10MW research reactor beamline.

Fast neutron imaging was performed using a beamline of the 10MW research reactor of the Budapest Neutron Centre, Hungary. A simple, low-cost 2D area detector has been used featuring a 8mm thick BC400 plastic scintillator converter screen and a CCD camera. A spatial resolution of around 1.3mm has been achieved. Typically 10min long exposures were needed to obtain reasonable quality radiographic images. For tomographic imaging typically several hours of acquisition were needed to obtain reasonable quality on non-symmetric and larger (e.g. 10×10×10cm3) objects. Due to the presence of a significant gamma background at the experimental position, massive (30cm thick) lead shielding and filtering was applied to the beam. The gamma contribution was mostly baseline independent of the object imaged and therefore could be subtracted, whereas the direct gamma contribution from the beam to the imaging detector signal is estimated to be less than 1%.

Acetyl-L-carnitine and oxaloacetate in post-treatment against LTP impairment in a rat ischemia model. An in vitro electrophysiological study.

A high proportion of research relating to cerebral ischemia focuses on neuroprotection. The application of compounds normally present in the organism is popular, because they do not greatly influence the synaptic activity by receptor modulation, and can be administered without serious side effects. Oxaloacetate (OxAc) and acetyl-L-carnitine (ALC) are such favorable endogenous molecules. ALC can exert a protective effect by improving the energy state of the neurons under ischemic conditions. A promising neuroprotective strategy is glutamate scavenging, which can be achieved by the intravenous administration of OxAc. This study involved the possible protective effects of ALC and OxAc in different post-treatment protocols against long-term potentiation (LTP) impairment. Ischemia was induced in rats by 2-vessel occlusion, which led to a decreased LTP relative to the control group. High-dose (200 mg/kg) ALC or OxAc post-treatment resulted in a higher potentiation relative to the 2VO group, but it did not reach the control level, whereas low-dose ALC (100 mg/kg) in combination with OxAc completely restored the LTP function. Many previous studies have concluded that ALC can be protective only as pretreatment. The strategy described here reveals that ALC can also be neuroprotective when utilized as post-treatment against ischemia.

Neuroprotective effect of oxaloacetate in a focal brain ischemic model in the rat.

During an ischemic event, the well-regulated glutamate (Glu) homeostasis is disturbed, which gives rise to extremely high levels of this excitatory neurotransmitter in the brain tissues. It was earlier reported that the administration of oxaloacetate (OxAc) as a Glu scavenger reduces the Glu level in the brain by enhancing the brain-to-blood Glu efflux. Here, we studied the neuroprotective effect of OxAc administration in a new focal ischemic model in rats. Occlusion of the middle cerebral artery resulted in immediate reduction of the somatosensory-evoked responses (SERs), and the amplitudes remained at the reduced level throughout the whole ischemic period. On reperfusion, the SERs started to increase, but never reached the control level. OxAc proved to be protective, since the amplitudes started to recover even during the ischemia, and finally fully regained the control level. The findings of the histological measurements were in accordance with the electrophysiological data. After Fluoro Jade C staining, significantly fewer labeled cells were detected in the OxAc-treated group relative to the control. These results provide new evidence of the neuroprotective effect of OxAc against ischemic injury, which strengthens the likelihood of its future applicability as a novel neuroprotective agent for the treatment of ischemic stroke patients.

The Use of Neutron Analysis Techniques for Detecting The Concentration And Distribution of Chloride Ions in Archaeological Iron.

Chloride (Cl) ions diffuse into iron objects during burial and drive corrosion after excavation. Located under corrosion layers, Cl is inaccessible to many analytical techniques. Neutron analysis offers non-destructive avenues for determining Cl content and distribution in objects. A pilot study used prompt gamma activation analysis (PGAA) and prompt gamma activation imaging (PGAI) to analyse the bulk concentration and longitudinal distribution of Cl in archaeological iron objects. This correlated with the object corrosion rate measured by oxygen consumption, and compared well with Cl measurement using a specific ion meter. High-Cl areas were linked with visible damage to the corrosion layers and attack of the iron core. Neutron techniques have significant advantages in the analysis of archaeological metals, including penetration depth and low detection limits.

Real-time RT-PCR assay to differentiate clades of H5N1 avian influenza viruses circulating in Vietnam.

Continued circulation and geographical expansion of highly pathogenic avian influenza H5N1 virus have led to the emergence of numerous clades in Vietnam. Although viral RNA sequencing and phylogenetic analysis are the gold standard for H5N1 HA clade designation, limited sequencing capacity in many laboratories precludes rapid H5N1 clade identification and detection of novel viruses. Therefore, a Taqman real-time RT-PCR assay for rapid differentiation of the four major H5N1 clades detected in Vietnam was developed. Using HA sequence alignments of clades 1.1, 2.3.2.1, 2.3.4, and 7 viruses, primers and FAM-labeled probes were designed to target conserved regions characteristic of each clade. The assay was optimized and evaluated using circulating clades of H5N1 collected in Vietnam from 2007 to 2012 and shown to be both sensitive and specific for the differentiation of the four H5N1 clades. The assay provides a useful tool for screening of large specimen collections for HA gene sequencing and phylogenetic analysis and for the rapid identification of molecular clade signatures to support outbreak investigations and surveillance activities. Finally, this assay may be useful to monitor for the emergence of novel or variant clades of H5N1 in Vietnam in the future or in other countries where these particular clades may circulate.

Post-ischemic treatment with L-kynurenine sulfate exacerbates neuronal damage after transient middle cerebral artery occlusion.

Since brain ischemia is one of the leading causes of adult disability and death, neuroprotection of the ischemic brain is of particular importance. Acute neuroprotective strategies usually have the aim of suppressing glutamate excitotoxicity and an excessive N-methyl-d-aspartate (NMDA) receptor function. Clinically tolerated antagonists should antagonize an excessive NMDA receptor function without compromising the normal synaptic function. Kynurenic acid (KYNA) an endogenous metabolite of the tryptophan metabolism, may be an attractive neuroprotectant in this regard. The manipulation of brain KYNA levels was earlier found to effectively enhance the histopathological outcome of experimental ischemic/hypoxic states. The present investigation of the neuroprotective capacity of L-kynurenine sulfate (L-KYNs) administered systemically after reperfusion in a novel distal middle cerebral artery occlusion (dMCAO) model of focal ischemia/reperfusion revealed that in contrast with earlier results, treatment with L-KYNs worsened the histopathological outcome of dMCAO. This contradictory result indicates that post-ischemic treatment with L-KYNs may be harmful.

Radioactivity of natural and artificial building materials - a comparative study.

Building materials and their additives contain radioactive isotopes, which can increase both external and internal radioactive exposures of humans. In this study Hungarian natural (adobe) and artificial (brick, concrete, coal slag, coal slag concrete and gas silicate) building materials were examined. We qualified 40 samples based on their radium equivalent, activity concentration, external hazard and internal hazard indices and the determined threshold values of these parameters. Absorbed dose rate and annual effective dose for inhabitants living in buildings made of these building materials were also evaluated. The calculations are based on (226)Ra, (232)Th and (40)K activity concentrations determined by gamma-ray spectrometry. Measured radionuclide concentrations and hence, calculated indices and doses of artificial building materials show a rather disparate distribution compared to adobes. The studied coal slag samples among the artificial building materials have elevated (226)Ra content. Natural, i.e. adobe and also brick samples contain higher amount of (40)K compared to other artificial building materials. Correlation coefficients among radionuclide concentrations are consistent with the values in the literature and connected to the natural geochemical behavior of U, Th and K elements. Seven samples (coal slag and coal slag concrete) exceed any of the threshold values of the calculated hazard indices, however only three of them are considered to be risky to use according to the fact that the building material was used in bulk amount or in restricted usage. It is shown, that using different indices can lead to different conclusions; hence we recommend considering more of the indices at the same time when building materials are studied. Additionally, adding two times their statistical uncertainties to their values before comparing to thresholds should be considered for providing a more conservative qualification. We have defined radon hazard portion to point to the limitations of the internal hazard considerations based on only measured (226)Ra activity concentrations without direct radon measurements. Our data are compared to those obtained in other countries and they provide a good basis to expand the database of radioactivity of building materials and gives information about the safety and situation of the building material industry in this central region of Europe.

Fundamental interstrain differences in cortical activity between Wistar and Sprague-Dawley rats during global ischemia.

Four-vessel occlusion (4VO), a frequently used model of global cerebral ischemia in rats, results in a dysfunction in wide brain areas, including the cerebral cortex and hippocampus. However, there are pronounced differences in response to global ischemia between the laboratory rat strains used in these studies. In the present work, the immediate acute effects of 4VO-induced global ischemia on the spontaneous electrocorticogram (ECoG) signals were analyzed in Wistar and Sprague-Dawley rats. The ECoG was isoelectric during the 10 min of global cerebral ischemia in Wistar rats and the first burst (FB) was seen 10-13 min after the start of reperfusion. In Sprague-Dawley rats, the FB was detected immediately after the start of 4VO or a few seconds later. The burst suppression ratio (BSR) in Wistar rats decreased to 45% in 5 min after FB, and after 25 min it was approximately 40%. In Sprague-Dawley rats, the BSR was 55% immediately after the FB and it decreased steeply to reach 0% by 10 min. There was also a significant difference between the two strains in the frequency composition of the ECoG pattern. The power spectral densities of the two strains differed virtually throughout the post-ischemic state. The histological results (Evans Blue, Cresyl Violet and Fluoro Jade C stainings) supplemented the electrophysiological data: the neuronal damage in the CA1 pyramids in Wistar rats was severe, whereas in the Sprague-Dawley animals it was only partial. These observations clearly demonstrate that the use of different rat strains (e.g. Wistar vs. Sprague-Dawley) can be a source of considerable variability in the results of acute experiments on global ischemia and it is important that the laboratory rats used in such experiments should be carefully chosen.

Relevance of the genetic polymorphism of NOD1 in Chlamydia pneumoniae seropositive stroke patients.

BACKGROUND AND PURPOSE: Chronic infections with certain pathogens, such as Chlamydia pneumoniae, and genetic parameters that influence inflammatory reactions have been suggested to contribute to ischaemic stroke. NOD1 is a potent cytosolic receptor for C. pneumoniae. The aim of this study was to investigate the genetic polymorphism of NOD1 from the aspect of the development of stroke. MATERIALS AND METHODS: A total of 280 patients with ischaemic stroke were enrolled in the study; 150 healthy blood donors served as controls. The G796A (E266K) NOD1 polymorphism was determined by restriction fragment length polymorphism. Chlamydia pneumoniae seropositivity was tested by ELISA. RESULTS: There was a significant difference in NOD1 G796A genotype distribution between the controls and the stroke patients with C. pneumoniae seropositivity. The AA homozygote and GA heterozygote mutant variants were detected in 16% (25 of 152) and in 50% (77 of 152) of the C. pneumoniae-positive stroke patients, as compared with 8% (6 of 84), and 28% (24 of 84), respectively, in the C. pneumoniae-positive healthy controls. (OR = 2.559; 95% CI = 1.105-6.517, P = 0.04 and OR = 2.567; 95% CI = 1.451-4.540 P < 0.001, respectively). The stroke patients with the large vessel pathology exhibited the highest frequency of the mutant allele A (51%). In contrast, amongst the C. pneumoniae-negative subjects, no difference in genotype frequency was observed between the stroke patients and the controls. CONCLUSION: Polymorphism in NOD1 G796A alone did not prove to be a risk factor for stroke in general, but in association with C. pneumoniae infection it appeared to be accompanied by an increased risk of the development of stroke.

Prevalence and genotyping of group 3 torque teno viruses detected in health care workers in Hungary.

Torque teno viruses (TTVs) are classified into the Anellovirus genus of the Circoviridae family. In addition to TTV isolates, TTV genogroup 3 also includes the 8 virus strains known as SENV-A to H. In this study, the prevalence of TTV group 3 viruses and that of SENV-D and H in particular were determined among the staff of a hospital in Budapest. Viruses were genotyped using type-specific PCR primers and by cloning and sequencing of PCR products. Frequency of infection with TTV group 3 was high among both the hospital staff and the control group. Prevalence of SENV-H was similar in the two groups, but SENV-D infection was significantly more common in the study group than in controls. Sequencing of PCR products showed that viruses closely related to isolate TUS01 are common in Hungary. Several sequences could not be genotyped and may represent a previously undescribed genotype within the genogroup. TTV group 3 sequences detected in the serum samples of a symptomless health care worker were followed-up for 15 years. Some strains persisted for up to 10 years, while others caused transient infections and could be detected in only one of the samples. Results showed that TTV infection, superinfection, and viral clearance often occur over the years without apparent symptoms.

Inflammatory- and immune responses in relation to bacterial replication in mice following re-infections with Chlamydophila pneumoniae.

OBJECTIVE: Investigation of chronic infections with Chlamydophila pneumoniae. METHODS: BALB/c mice were repeatedly infected with C. pneumoniae and tested during a 1-year period. Production of histamine, IFN-gamma, IL-6 and antibodies was monitored by ELISA. Live bacteria were cultured and DNA was detected by PCR. Cellular immunity was tested by ELISPOT. RESULTS: After re-infections, culture positivity and persistence of DNA in lungs and blood were shorter. Detection of DNA at late time points indicated persistent infection in a few mice. Histamine was produced after primary and re-infections, and the level correlated with the number of viable bacteria in lung. IFN-gamma, IL-6 levels, IgG2/IgG1 ratio, IgA titres, and level of chlamydial heat-shock protein antibodies were higher after re-infections. IgM antibodies were demonstrated even after re-infections. High number of IFN-gamma-producing splenocytes was observed after the third inoculation. CONCLUSION: These results promote an understanding of the patho- and immune mechanisms after C. pneumoniae re-infections.

Chronic infections and histamine, CRP and IL-6 levels after percutaneous transluminal coronary angioplasty.

OBJECTIVE AND DESIGN: Our hypothesis was that percutaneous transluminal coronary angioplasty (PTCA) reactivates certain pathogens that contribute to inflammatory processes after the intervention. SUBJECTS: We determined the levels of antibodies to human Hsp60 and levels of histamine, CRP and IL-6 in sera from 28 patients of unstable angina prior to and on days 4 and 14 after PTCA. We compared the presence of Chlamydophila pneumoniae (Cpn) and human cytomegalovirus (HCMV) DNA in peripheral blood, and levels of antibodies to Cpn, HCMV, herpes simplex virus, Epstein-Barr virus and mycobacterial Hsp65 in the serum. RESULTS: Higher prevalence of Cpn and HCMV DNA was demonstrated after PTCA than before, but titers of antibodies to the pathogens did not increase. Levels of histamine, CRP and IL-6 were enhanced after PTCA. There was no association between the levels of histamine, CRP and IL-6 and the rate of pathogen DNA, or antibody titers to the pathogens, except an association between Cpn IgA and histamine levels before PTCA. CONCLUSIONS: Reactivation of Cpn and HCMV and inflammatory change characterized by increased levels of histamine, CRP and IL-6 following PTCA are suggested. An association might exist between Cpn IgA antibody and histamine levels in patients of unstable angina.

A soluble factor(s) released by MRC-5 cells early and late after human cytomegalovirus infection induces maturation of monocyte-derived dendritic cells.

A human cytomegalovirus (HCMV) strain passaged 10 times on MRC-5 human fibroblast cells failed to express immediate early (IE) antigens in immature dendritic cells (iDCs) after infection. However, both the early and the late HCMV conditioning medium, harvested from MRC-5 cells at 24 h or 7-9 days after infection, respectively, induced a higher ratio of DCs expressing maturation markers (CD40, CD83, CD86 and HLA-DR) on the surface of the cells. HCMV conditioning medium, ultracentrifuged to remove virus particles, exhibited a similarly enhanced expression of DC maturation markers. DCs treated with HCMV conditioning medium harvested late after infection increased the percentages of autologous CD4+ and CD8+ cells of seropositive donors to produce IFN-gamma and stimulated HCMV-specific lymphoproliferative responses. The early HCMC conditioning medium was also able to induce the functional maturation of DCs, as demonstrated by supplementing this medium with a Chlamydia pneumoniae antigen.

Chlamydophila pneumoniae and human cytomegalovirus in atherosclerotic carotid plaques--combined presence and possible interactions.

The aim of our study was to investigate the combination of Chlamydophila pneumoniae and human cytomegalovirus (HCMV) as a pathogenic factor in atherosclerosis. Accordingly, we tested by means of PCR and immunohistochemistry the presence of these pathogens in the same atherosclerotic carotid specimen. The histology of the samples and the patients' antibodies against these pathogens were evaluated. Further, we examined the impact of C. pneumoniae and HCMV infection on the gene expression of the human monocytic cell line U937. Six of the 22 samples contained only C. pneumoniae, 4 contained only HCMV, 7 contained both C. pneumoniae DNA and/or antigens of both pathogens, and 5 samples were negative. No correlation was found between the presence of these microbes and either the cellular structure of the plaques, or the serostatus of the patients. The infection of U937 cells with HCMV and especially C. pneumoniae induced inflammation and atherosclerosis-related genes. Furthermore, the doubly-infected cells produced higher levels of the mRNA of pro-platelet basic protein and fatty acid binding protein 4. In conclusion, C. pneumoniae is often present in combination with HCMV in atherosclerotic carotid lesions. The in vitro coinfection model reveals that the doubly-infected monocytes are potent expressors of proatherosclerotic genes, suggesting that this coinfected population may accelerate the process of atherosclerosis.

Radionuclides in fruit systems: model prediction-experimental data intercomparison study.

This paper presents results from an international exercise undertaken to test model predictions against an independent data set for the transfer of radioactivity to fruit. Six models with various structures and complexity participated in this exercise. Predictions from these models were compared against independent experimental measurements on the transfer of 134Cs and 85Sr via leaf-to-fruit and soil-to-fruit in strawberry plants after an acute release. Foliar contamination was carried out through wet deposition on the plant at two different growing stages, anthesis and ripening, while soil contamination was effected at anthesis only. In the case of foliar contamination, predicted values are within the same order of magnitude as the measured values for both radionuclides, while in the case of soil contamination models tend to under-predict by up to three orders of magnitude for 134Cs, while differences for 85Sr are lower. Performance of models against experimental data is discussed together with the lessons learned from this exercise.

Identifying optimal agricultural countermeasure strategies for a hypothetical contamination scenario using the strategy model.

A spatially implemented model designed to assist the identification of optimal countermeasure strategies for radioactively contaminated regions is described. Collective and individual ingestion doses for people within the affected area are estimated together with collective exported ingestion dose. A range of countermeasures are incorporated within the model, and environmental restrictions have been included as appropriate. The model evaluates the effectiveness of a given combination of countermeasures through a cost function which balances the benefit obtained through the reduction in dose with the cost of implementation. The optimal countermeasure strategy is the combination of individual countermeasures (and when and where they are implemented) which gives the lowest value of the cost function. The model outputs should not be considered as definitive solutions, rather as interactive inputs to the decision making process. As a demonstration the model has been applied to a hypothetical scenario in Cumbria (UK). This scenario considered a published nuclear power plant accident scenario with a total deposition of 1.7x10(14), 1.2x10(13), 2.8x10(10) and 5.3x10(9)Bq for Cs-137, Sr-90, Pu-239/240 and Am-241, respectively. The model predicts that if no remediation measures were implemented the resulting collective dose would be approximately 36 000 person-Sv (predominantly from 137Cs) over a 10-year period post-deposition. The optimal countermeasure strategy is predicted to avert approximately 33 000 person-Sv at a cost of approximately 160 million pounds. The optimal strategy comprises a mixture of ploughing, AFCF (ammonium-ferric hexacyano-ferrate) administration, potassium fertiliser application, clean feeding of livestock and food restrictions. The model recommends specific areas within the contaminated area and time periods where these measures should be implemented.