Outcomes and regional differences in practice in a worldwide coronary stent registry.

Objective: The primary objective was to assess the performance of a new generation thin-strut sirolimus-eluting coronary stent with abluminal biodegradable polymer in an all comer population. The secondary objective was to detail differences in contemporary percutaneous coronary intervention (PCI) practice worldwide.

Methods: e-Ultimaster was an all-comer, prospective, global registry (NCT02188355) with independent event adjudication enrolling patients undergoing PCI with the study stent.

Training of public health personnel in handling CBRN emergencies: a table-top exercise card concept.

There is a large concern in the society today about the threat posed from releases of chemical, biological, radiological or nuclear (CBRN) materials, whether accidental or malicious. A rapid and adapted response to a CBRN incident combined with a thorough public communication is believed to decrease the detrimental impacts on health and to reduce the psychosocial effects. To facilitate CBRN exercises, which often can be regarded by non-specialists as rather complicated, a tool in the form of a set of Exercise cards for CBRN emergency response table-top exercises has been developed.

Survey on methodologies in the risk assessment of chemical exposures in emergency response situations in Europe.

A scientifically sound assessment of the risk to human health resulting from acute chemical releases is the cornerstone for chemical incident prevention, preparedness and response. Although the general methodology to identify acute toxicity of chemicals has not substantially changed in the last decades, there is ongoing debate on the current approaches for human health risk assessment in scenarios involving acute chemical releases. A survey was conducted to identify: (1) the most important present and potential future chemical incident scenarios and anticipated changes in chemical incidents or their management; (2) information, tools and guidance used in different countries to assess health risks from acute chemical releases; and (3) needs for new information, tools, guidance and expertise to enable the valid and rapid health risk assessment of acute chemical exposures.

SeQuentPlease World Wide Registry: clinical results of SeQuent please paclitaxel-coated balloon angioplasty in a large-scale, prospective registry study.

Objectives: This study sought to assess the safety and efficacy of paclitaxel-coated balloon (PCB) angioplasty in an international, multicenter, prospective, large-scale registry study.

Background: In small randomized trials, PCB angioplasty was superior to uncoated balloon angioplasty for treatment of bare-metal stent (BMS) and drug-eluting stent (DES) restenosis.

Methods: Patients treated with SeQuent Please PCBs were included.

An animal model to study health effects during continuous low-dose exposure to the nerve agent VX.

In the present study, we have developed an animal model to study long-term health effects of continuous exposure of toxic chemical agents, in awake, freely moving rats. The aim was to evaluate the effect of low-dose exposure of the nerve agent VX, and to find specific biomarkers for intoxication. To exclude the influence of stress, we used an implanted radio-telemetric device for online registration of physiological parameters, and an osmotic pump, implanted subcutaneously, for continuous exposure of the toxic agent.

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial: outcomes in patients receiving monotherapy.

In the main Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) report, we investigated outcomes in 15 245 high-risk hypertensive subjects treated with valsartan- or amlodipine-based regimens. In this report, we analyzed outcomes in 7080 patients (46.4%) who, at the end of the initial drug adjustment period (6 months), remained on monotherapy.

Effects of HI 6, diazepam and atropine on soman-induced IL-1 beta protein in rat brain.

The current treatment for soman-intoxication is the oxime HI 6 together with the anticholinergic drug atropine. This antidote combination is known to have effects on seizures, respiratory system, blood pressure and animal survival in experiments. However, the inflammatory responses following soman-intoxication leading to neuronal damage have not been fully evaluated.

Cardiopulmonary effects of HI-6 treatment in soman intoxication.

The cardiopulmonary effects of HI-6, together with atropine and soman, were studied in the rat. HI-6 is an effective antidote in acute poisoning with the nerve agent soman. The therapeutic efficiency of HI-6 is still unclear and cannot be explained entirely by the HI-6 reactivating ability of acetylcholinesterase (AChE).

Soman-induced interleukin-1 beta mRNA and protein in rat brain.

Exposure to high doses of the toxic organophosphate compound soman, also known as a chemical warfare agent, causes a progression of toxic symptoms including hyper-secretions, convulsions, respiratory depression, and finally death. In previous studies, we have demonstrated pronounced effects following soman intoxication in dopaminergic, GABAergic, and cholinergic systems in rat brain. The aim of this study was to investigate the effects on the pro-inflammatory cytokine interleukin-1beta (IL-1beta), indicated as mRNA and protein production, at different time intervals following soman intoxication.

Increased levels of nitrogen oxides and lipid peroxidation in the rat brain after soman-induced seizures.

We have investigated the effect of soman-induced seizures on rat brain levels of nitrogen oxides (NOx) and lipid peroxidation (LPO) 30 min and 24 h after intoxication. Following administration of soman (90 microg/kg s.c.

Effect of soman on N-methyl-D-aspartate-stimulated [3H]norepinephrine release from rat cortical slices.

Effects of soman on N-methyl-D-aspartate (NMDA) evoked [3H]norepinephrine (NE) release were examined in rat brain cortical slices. NMDA increased [3H]NE release in a concentration-dependent manner. Soman could inhibit the increase evoked by NMDA, but carbachol, an agonist of cholinergic receptor, could potentiate the increase evoked by NMDA.

Toxicokinetics of soman in cerebrospinal fluid and blood of anaesthetized pigs.

The toxicokinetics of the four stereoisomers of the nerve agent C(+/-)P(+/-)-soman was analysed in cerebrospinal fluid (CSF) and blood in anaesthetized, spontaneously breathing pigs during a 90-min period after injection of soman. The pigs were challenged with different intravenous (i.v.

Mechanisms Underlying the Inhibition of Soman on NMDA-stimulated [(3)H]Norepinephrine Release from Rat Cortical Slices, Role of Phospholipase C and Protein Kinase C.

Our previous studies indicated that soman inhibits N-methyl-d-aspartate (NMDA)-stimulated [(3)H]norepinephrine (NE) release from rat cortical slices by acting at a non-cholinergic site. In order to characterize the mechanisms, neomycin, a phospholipase C (PLC) inhibitor, and polymyxin B (PMB), a rather selective protein kinase C (PKC) inhibitor, were used to examine a possible involvement of PLC and PKC in the inhibitory effect of soman on NMDA-stimulated [(3)H]NE release. The role of pertussis toxin (PTX)-sensitive G-protein was also investigated by application of PTX.

Inhibition by soman of NMDA-stimulated [3H]norepinephrine release from rat cortical slices, studies of non-cholinergic effect.

Effects of soman, an irreversible cholinesterase (ChE) inhibitor, on [3H]norepinephrine (NE) release evoked by N-methyl-d-aspartate (NMDA) were studied in rat brain cortical slices. Soman inhibited NMDA-stimulated [3H]NE release in a concentration-dependent manner. This effect was neither reversed by atropine, an antagonist of the muscarinic receptor, nor by d-tubocurarine, an antagonist of the nicotinic receptor.

Enzyme-based microassay for accurate determination of soman in blood samples.

Successful medical therapy for nerve agent intoxication requires early diagnosis and treatment. Current clinical diagnostic methods do not permit early or definitive confirmation of intoxication. To improve the chances of successful medical therapy against nerve agent intoxication, a sensitive enzyme-based microassay for rapid and accurate quantification of residual soman levels in blood was developed.

Correlation between cortical EEG and striatal microdialysis in soman-intoxicated rats.

In vivo microdialysis and EEG recording have been used in order to study the combined neurochemical and electrophysiological events during intoxication with soman (o-1,2,2-trimethylpropyl methylphosphono-fluoridate), a potent inhibitor of acetylcholinesterase (AChE), in the freely moving rat. All rats exposed to soman exhibited signs of AChE inhibition. The duration of EEG recorded seizures after soman intoxication averaged 43 +/- 24 min.

Pharmacokinetics and effects of HI 6 in blood and brain of soman-intoxicated rats: a microdialysis study.

The bispyridinium oxime HI 6 (1-(((4-amino-carbonyl)pyridino)methoxy)methyl)-2-(hydroxyimino )methyl)-pyridinium dichloride monohydrate), combined with atropine, is effective for treating poisoning with organophosphate nerve agents. The protective action of HI 6 in soman poisoning has been attributed mainly to its peripheral reactivation of inhibited acetylcholinesterase. In the present study we investigated whether high intramuscular doses of HI 6 can reach the brain in a sufficient amount to reactivate inhibited brain acetylcholinesterase.

Release of dopamine, GABA and EAA in rats during intrastriatal perfusion with kainic acid, NMDA and soman: a comparative microdialysis study.

There is an increasing amount of experimental evidence that excitatory amino acids (EAAs) are involved in the brain lesions observed after severe intoxication with the highly toxic organophosphorus compound soman. This study was undertaken to compare the acute actions of soman, and the glutamatergic receptor agonists kainic acid and N-methyl-D-aspartate (NMDA) on striatal release of dopamine and amino acids. The neurotoxic compounds were administered in high (10 mM) concentrations by unilateral intrastriatal microdialysis perfusion in freely moving rats.

Measurement of the oxime HI-6 after peripheral administration in tandem with neurotransmitter levels in striatal dialysates: effects of soman intoxication.

In the present study, the technique of microdialysis combined with tandem high-performance liquid chromatography was used to determine the striatal levels of HI-6 and neurotransmitters following peripheral administration of HI-6 (50 mg/kg i.m.) in conscious, freely moving rats.

Pharmacokinetics of HI-6 and atropine in anaesthetized pigs after administration by a new autoinjector.

A newly developed autoinjector (Astra Tech, Sweden) containing 500 mg HI-6 and 2 mg atropine sulphate was tested in anaesthetized normal pigs. The pharmacokinetics and pharmacodynamics of the drugs after administration by the autoinjector were compared with those after conventional needle and syringe delivery intramuscularly and intravenously. Cardiopulmonary parameters were monitored and serum concentrations of oxime, atropine, and acetylcholinesterase were determined in blood samples taken at intervals over a 6 h period postinjection.

Estimation of the convulsive effect of cyanide in rats.

Convulsions are frequently observed in severe, acute cyanide intoxication. The mechanisms involved are not well known. In the present study, the convulsive effect of cyanide was examined in the rat by means of a dose threshold determination after infusion of cyanide.

Treatment of organophosphate poisoning in pigs: antidote administration by a new binary autoinjector.

The therapeutic effectiveness of a new binary autoinjector containing 500 mg HI-6 and 2 mg atropine sulphate was tested in anesthetized pigs poisoned by a lethal dose of soman i.v. (9 micrograms/kg per 20 min).

The effects of cyanide on the extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 5-hydroxyindoleacetic acid and inositol phospholipid breakdown in the brain.

The effects of sodium cyanide on the extracellular levels of dopamine and the main brain metabolites of dopamine and 5-hydroxytryptamine were studied in awake, freely moving rats using microdialysis technique. Already 20 min after the administration of cyanide (2 mg/kg; ip) the extracellular level of striatal dopamine was increased and after 40 min an enhancement of the homovanillic acid level was observed. Slight but significant decreases of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid were also observed.

Effects of cyanide in vitro on the activity of monoamine oxidase in striatal tissue from rat and pig.

We have shown previously in the rat that lethal, acute cyanide intoxication dramatically decreased the levels of dopamine (DA) in the striatum, while the synthesis of DA was increased. The main brain metabolite of DA, homovanillic acid, was also diminished. However, the levels of the oxidatively deaminated metabolite of DA, 3,4-dihydroxyphenylacetic acid, were not significantly changed.