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.

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.

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.

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.

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%.

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.

Independent and joint effects of antibodies to human heat-shock protein 60 and Chlamydia pneumoniae infection in the development of coronary atherosclerosis.

BACKGROUND: Studies have suggested that the prevalence of antibodies against heat-shock proteins (HSPs), Chlamydia pneumoniae (CPN), and cytomegalovirus (CMV) is associated with coronary artery disease (CAD), but the independent or joint effects of human (h) HSP60 antibodies and these pathogens in patients have not been fully elucidated. METHODS AND RESULTS: A total of 405 subjects (276 patients with CAD and 129 control individuals) were tested for serum antibodies to hHSP60, CPN, and CMV immediate-early-1 (IE1) antigens. Patients were also assessed for serum cholesterol, triglyceride levels, and smoking habit. Significantly elevated levels of antibodies to hHSP60 and CPN but not to CMV-IE1 antigens were documented in CAD patients. Multiple logistic regression analysis and subanalyses of selected subjects showed that these associations were independent of age, sex, smoking, and serum lipid levels. Antibodies to hHSP60 and CPN did not correlate quantitatively; however, the relative risk of disease development was substantially increased in subjects with high antibody levels to both hHSP60 and CPN:, reaching an odds ratio of 82.0 (95% CI 10.6 to 625.0). CONCLUSIONS: High levels of antibodies to hHSP60 and CPN: are independent risk factors for coronary atherosclerosis, but their simultaneous presence substantially increases the risk for disease development.

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.

Chlamydia pneumoniae in atherosclerotic middle cerebral artery.

BACKGROUND AND PURPOSE: Atherosclerotic middle cerebral arteries are frequent sites of thrombosis, leading to stroke. Previous studies have suggested a role for Chlamydia pneumoniae in the pathogenesis of atherosclerosis. However, the presence of this pathogen in atherosclerotic middle cerebral arteries has heretofore not been documented. In the present study, we analyzed atheromatous plaques from middle cerebral arteries for the presence of C pneumoniae. METHODS: Atherosclerotic middle cerebral arteries from 15 cadavers who died of natural causes and corresponding nonatherosclerotic arteries from 4 otherwise healthy trauma victims were examined. Assays for C pneumoniae DNA were carried out by nested polymerase chain reaction (nPCR) specific for the C pneumoniae ompA gene. The presence of the bacterium was assessed by transmission electron microscopy. RESULTS: Five of the 15 atherosclerotic arterial samples and none of the control tissues were positive for C pneumoniae by nPCR. Particles similar in morphology and size to C pneumoniae elementary bodies were detected by transmission electron microscopy in 4 of the 5 nPCR-positive atherosclerotic samples. CONCLUSIONS: The demonstration of C pneumoniae in atherosclerotic middle cerebral arteries is consistent with the hypothesis that this bacterium is involved in acute and chronic cerebrovascular diseases.

Kynurenine administered together with probenecid markedly inhibits pentylenetetrazol-induced seizures. An electrophysiological and behavioural study.

The kynurenine pathway converts tryptophan into various compounds, including l-kynurenine, which in turn can be converted to the excitatory amino acid receptor antagonist kynurenic acid, which may therefore serve as a protective agent in such neurological disorders as epileptic seizures. Kynurenic acid, however, has a very limited ability to cross the blood-brain barrier, whereas kynurenine passes the barrier easily. In this study, we tested the hypothesis that kynurenine administered systemically together with probenecid, which inhibits kynurenic acid excretion from the cerebrospinal fluid, results in an increased level of kynurenic acid in the brain that is sufficiently high to provide protection against the development of pentylentetrazol-induced epileptic seizures. CA3 stimulation-evoked population spike activity was recorded from the pyramidal layer of area CA1 of the rat hippocampus, and in another series of behavioural experiments, water maze and open-field studies were carried out to test the presumed protective effect of kynurenine + probenecid pre-treatment against pentylenetetrazol-induced seizures. This study has furnished the first electrophysiological proof that systemic kynurenine (300 mg/kg, i.p.) and probenecid (200 mg/kg, i.p.) administration protects against pentylenetetrazol-induced (60 mg/kg, i.p.) epileptic seizures.

Activation of the primary motor cortex by somatosensory stimulation in adult rats is mediated mainly by associational connections from the somatosensory cortex.

In anaesthetized adult rats, facial nerve injury causes a disinhibition of the interhemispheric connections between homotopic representation fields in the primary motor cortex with a latency of 4 min (Toldi et al., 1996, Neurosci Lett. 203, 179-182). One possible explanation for the induction of such rapid changes is an alteration of the somatosensory input to the motor cortex. To test this hypothesis, unit activity in primary motor cortex was recorded during electrical stimulation of trigeminal afferents in the contralateral whisker-pad. About one-third of all recorded primary motor cortex neurons responded with latencies shorter than in the ventrolateral and posterior nuclei of the thalamus. Responses failed at stimulation frequencies > or = 10 Hz and after elimination or inactivation of the somatosensory cortex. Within primary motor cortex, the activatable neurons displayed a bilaminar distribution and were identified as pyramidal neurons by neurobiotin labelling. The results suggest that trigeminal afferents participate in modulation of the activity of primary motor cortex output neurons via primary somatosensory cortex-to-primary motor cortex associational connections, even under anaesthesia.

In vivo efficacy of SDZ 35-682, a new picornavirus capsid-binding agent.

SDZ 35-682 is a potent and selective inhibitor of the replication of members of the picornavirus group. It belongs to the group of uncoating inhibitors binding to the hydrophobic pocket in the capsid of the virion. In cell culture it inhibits several rhinovirus serotypes and echovirus 9 at concentrations as low as 0.1 micrograms/ml. In the echovirus 9 animal model the protective effect of SDZ 35-682 was found to be dependent on both, dose of drug and duration of treatment. Significant protection of newborn mice from paralysis and death could be achieved by either a high dose (126 mg/kg) given only twice, at days 0 and 1 relative to echovirus 9 inoculation, or by a lower dose administered for 4 or 6 days. This finding might be explained by assuming a long half-life for SDZ 35-682. Though clinical usefulness of SDZ 35-682 may be limited by its relatively narrow antiviral spectrum it represents a novel potent and selective inhibitor of rhinovirus and echovirus 9 replication in cell culture and in the organism.

SDZ 35-682, a new picornavirus capsid-binding agent with potent antiviral activity.

SDZ 35-682 is a potent and selective inhibitor of the replication of members of the picornavirus group. It inhibits several rhinovirus serotypes and echovirus 9 at concentrations as low as 0.1 micrograms/ml, without exerting any effect on cell proliferation up to 30 micrograms/ml. As observed with other capsid-binding antipicornavirus compounds, there is a wide variation in sensitivity of the different serotypes within the rhinovirus group. The point of interference of SDZ 35-682 in a single cycle of virus growth is an early event taking place before 2 or 3 h of echo- or rhinovirus replication, respectively. By incorporation of neutral red into the viral capsid and measurement of acquisition of photoresistance it is shown that uncoating of echovirus 9 is inhibited by SDZ 35-682. In addition, efficiency of adsorption of echovirus 9 is reduced by SDZ 35-682. To demonstrate that SDZ 35-682, like other uncoating inhibitors of picornaviruses, binds to the hydrophobic pocket beneath the canyon floor co-crystallization with HRV 14 was performed. Considerable conformational changes occur in VP1 in the HRV 14/SDZ 35-682 complex. SDZ 35-682 is 19 A long from end to end and thus fills the entire hydrophobic pocket including its innermost end; it is less flexible than other long antiviral agents. It has been suggested that compounds filling the entire hydrophobic pocket will affect the uncoating process of the virion. Thus, inhibition of viral uncoating, as demonstrated with echovirus 9, probably is the predominant mode of action of SDZ 35-682.

Estrogen effects on arcuate neurons in rat. An in situ electrophysiological study.

In acute experiments, the effects of i.p. 17beta-estradiol on the activity of arcuate neurons were studied in ovariectomized rats. 17Beta-estradiol (100 microg/100g, i.p.) increased the spontaneous activity of the observed arcuate neurons with a latency of 20-25 min. In some neurons spontaneous activity could be influenced by stimulation of the olfactory and somatosensory systems. Activation of the trigeminal system significantly increased the spontaneous activity of the studied units, while stimulation of the accessory olfactory bulb decreased it, both with and without 17beta-estradiol treatment. It is suggested that the 20-25 min latency of the 17beta-estradiol effect is based not so much on membrane as on genomic mechanisms. This suggestion is supported by immunocytochemical studies: 17beta-estradiol treatment significantly decreased the number of GABA-positive axo-somatic synapses in the arcuate nucleus.

The modulatory effect of estrogen on the neuronal activity in the barrel cortex of the rat. An electrophysiological study.

In acute experiments, the effects of iontophoretically applied 17 beta-estradiol hemisuccinate on the activity of the primary somatosensory cortical neurons were studied in ovariectomized rats by extracellular single-unit recording. 17 beta-Estradiol increased both the spontaneous and the vibrissa deflection-evoked responses, with an average latency of 24 min. It is suggested that this relatively long latency of the 17 beta-estradiol effect is based not so much on membrane mechanisms as on genomic mechanisms.

Septamycin, a polyether antibiotic. Taxonomy, fermentation, isolation and characterization.

Septamycin is a metal complexing polyether antibiotic produced by a strain of Streptomyces hygroscopicus NRRL 5678. The metabolite, a monocarboxylic acid, was isolated as the sodium salt C48H81NaO16. The crystal structure and absolute configuration were established by X-ray analysis of the p-bromophenacyl derivative. Septamycin has a thirty-carbon backbone and contains seven heterocyclic rings. Supported by direct comparison septamycin proved to be identical with antibiotic A28695 A isolated from Streptomyces albus NRRL 3883. The metabolite is active against gram-positive bacteria and Eimeria tenella (chicken coccidiosis).

Determination and use of the monetary values of the averted person-sievert for use in radiation protection decisions in Hungary.

The monetary value of the averted dose is a key element in the implementation of the optimization principle both in radiation praxis and intervention. The main concept of this principle is to select options so as to maintain exposures at a reasonable level. The feature of this concept is to look for the minimal total cost, i.e., the sum of the costs of protection and health detriment. In its publications, ICRP emphasized the need for developing models which also take into account the "subjective" aspects of health detriment in the optimization process, such as the perception of risk by individuals and the need to put more emphasis on equity in the distribution of individual doses. This paper proposes a modified alpha-value model based on CEPN's model (Centre d'Etude sur L'Evaluation de la Protection dans le Domaine Nucleaire) to put more emphasis on recently published considerations about the smaller effects of the portion of collective dose derived from small doses. The parameters of the monetary value of unit collective dose averted, which is a key element of this type of model, can be estimated by means of approaches like human capital (HC) and willingness to pay (WTP) from the point of view of economic theories. The present study summarizes the results achieved by WTP among the radiation specialists mainly from the Paks Nuclear Power Plant, Hungary. The aim of the effort was to determine the value of a statistical life and the monetary value of a unit person-sievert associated with averted occupational exposure due to ionizing radiation. To apply the WTP method, a questionnaire has been prepared on the basis of the one introduced by CEPN in the late 1990's. The investigations show that the value of US$6,200 person-Sv(-1) seems to be acceptable for the alphabase-value for the occupational situation in Hungary in 1999. WTP assessments should be applied with caution since the economic level of the country, the workplace surveyed, and the computational methods affect the results. In addition, achieving a high level safety culture must rely on international cooperation both from the theoretical and practical viewpoints, and international markets affect the associated costs. Therefore the monetary requirements cannot always be assessed solely on a national basis.