Non-contrast-enhanced MRA of renal artery stenosis: validation against DSA in a porcine model.

OBJECTIVES: To compare 3D-inversion-recovery balanced steady-state free precession (IR-bSSFP) non-contrast-enhanced magnetic resonance angiography (MRA) with 3D-contrast-enhanced MRA (CE-MRA) for assessment of renal artery stenosis (RAS) using digital subtraction angiography (DSA) as the reference standard. METHODS: Bilateral RAS were surgically created in 12 swine. IR-bSSFP and CE-MRA were acquired at 1.5 T and compared to rotational DSA. Three experienced cardiovascular radiologists evaluated the IR-bSSFP and CE-MRA studies independently. Linear regression models were used to calibrate and assess the accuracy of IR-bSSFP and CE-MRA, separately, against DSA. The coefficient of determination and Cohen's kappa coefficient were also generated. RESULTS: Calibration of the three readers' RAS grading revealed R(2) values of 0.52, 0.37 and 0.59 for NCE-MRA and 0.48, 0.53 and 0.71 for CE-MRA. Inter-rater agreement demonstrated Cohen's kappa values ranging from 0.25 to 0.65. Distal renal artery branch vessels were visible to a significantly higher degree with NCE-MRA compared to CE-MRA (p < 0.001). Image quality was rated excellent for both sequences, although image noise was higher with CE-MRA (p < 0.05). In no cases did noise interfere with image interpretation. CONCLUSIONS: In a well-controlled animal model of surgically induced RAS, IR-bSSFP based NCE-MRA and CE-MRA accurately graded RAS with a tendency for stenosis overestimation, compared to DSA. KEY POINTS: • IR-bSSFP and CE-MRA are accurate methods for diagnosis of renal artery stenosis • IR-bSSFP and CE-MRA demonstrate excellent agreement with DSA • Both IR-bSSFP and CE-MRA have a tendency to overestimate renal artery stenosis.

Deep brain stimulation for tremor resulting from acquired brain injury.

OBJECTIVES: To evaluate the efficacy of deep brain stimulation (DBS) in the treatment of tremor resulting from acquired brain injury (ABI). METHODS: A series of eight consecutive patients with post-ABI tremor were treated with DBS of the ventro-oralis posterior (VOP)/zona incerta (ZI) region, and subsequently underwent blinded assessments using Bain's tremor severity scale. RESULTS: VOP/ZI DBS produced a mean reduction in tremor severity of 80.75% based on Bain's tremor severity scale, with significant reductions in all five component tremor subscores: rest, postural, kinetic, proximal and distal. No adverse neurological complications were reported, although one patient experienced exacerbation of pre-existing gait ataxia. CONCLUSION: VOP/ZI stimulation is demonstrated here to be an effective and safe approach for the treatment of post-ABI tremor in the largest series published at the time of writing.

Local field potentials reveal a distinctive neural signature of cluster headache in the hypothalamus.

Cluster headache (CH) is a debilitating neurovascular condition characterized by severe unilateral periorbital head pain. Deep brain stimulation of the posterior hypothalamus has shown potential in alleviating CH in its most severe, chronic form. During surgical implantation of stimulating macroelectrodes for cluster head pain, one of our patients suffered a CH attack. During the attack local field potentials displayed a significant increase in power of approximately 20 Hz. To the authors' knowledge, this is the first recorded account of neuronal activity observed during a cluster attack. Our results both support and extend the current literature, which has long implicated hypothalamic activation as key to CH generation, predominantly through indirect haemodynamic neuroimaging techniques. Our findings reveal a potential locus in CH neurogenesis and a potential rationale for efficacious stimulator titration.

Model testing of radioactive contamination by 90Sr, 137Cs and 239,240Pu of water and bottom sediments in the Techa River (Southern Urals, Russia).

This paper presents results of testing models for the radioactive contamination of river water and bottom sediments by (90)Sr, (137)Cs and (239,240)Pu. The scenario for the model testing was based on data from the Techa River (Southern Urals, Russia), which was contaminated as a result of discharges of liquid radioactive waste into the river. The endpoints of the scenario were model predictions of the activity concentrations of (90)Sr, (137)Cs and (239,240)Pu in water and bottom sediments along the Techa River in 1996. Calculations for the Techa scenario were performed by six participant teams from France (model CASTEAUR), Italy (model MARTE), Russia (models TRANSFER-2, CASSANDRA, GIDRO-W) and Ukraine (model RIVTOX), all using different models. As a whole, the radionuclide predictions for (90)Sr in water for all considered models, (137)Cs for MARTE and TRANSFER-2, and (239,240)Pu for TRANSFER-2 and CASSANDRA can be considered sufficiently reliable, whereas the prediction for sediments should be considered cautiously. At the same time the CASTEAUR and RIVTOX models estimate the activity concentrations of (137)Cs and (239,240)Pu in water more reliably than in bottom sediments. The models MARTE ((239,240)Pu) and CASSANDRA ((137)Cs) evaluated the activity concentrations of radionuclides in sediments with about the same agreement with observations as for water. For (90)Sr and (137)Cs the agreement between empirical data and model predictions was good, but not for all the observations of (239,240)Pu in the river water-bottom sediment system. The modelling of (239,240)Pu distribution proved difficult because, in contrast to (137)Cs and (90)Sr, most of models have not been previously tested or validated for plutonium.

Abnormal thalamocortical dynamics may be altered by deep brain stimulation: using magnetoencephalography to study phantom limb pain.

Deep brain stimulation (DBS) is used to alleviate chronic pain. Using magnetoencephalography (MEG) to study the mechanisms of DBS for pain is difficult because of the artefact caused by the stimulator. We were able to record activity over the occipital lobe of a patient using DBS for phantom limb pain during presentation of a visual stimulus. This demonstrates that MEG can be used to study patients undergoing DBS provided control stimuli are used to check the reliability of the data. We then asked the patient to rate his pain during and off DBS. Correlations were found between these ratings and power in theta (6-9) and beta bands (12-30). Further, there was a tendency for frequencies under 25 Hz to correlate with each other after a period off stimulation compared with immediately after DBS. The results are interpreted as reflecting abnormal thalamocortical dynamics, previously implicated in painful syndromes.

The alpha4beta1 integrin in sickle cell disease.

The alpha4beta1 integrin is an adhesion receptor expressed on reticulocytes in sickle cell disease (SCD) and mediates the adhesion of these cells to sub-endothelial matrix proteins and the endothelium. In this review, we describe the mechanism of activation of the alpha4beta1 integrin on sickle reticulocytes and discuss novel roles for this integrin in SCD as a result of this activation. We also illustrate novel therapies in SCD that may target the integrin and alleviate vaso-occlusion.

Activation of sickle red blood cell adhesion via integrin-associated protein/CD47-induced signal transduction.

Peripheral human red blood cells (RBCs) are not generally known to become activated and adhesive in response to cell signaling. We show, however, that soluble thrombospondin via integrin-associated protein (IAP; CD47) increases the adhesiveness of sickle RBCs (SS RBCs) by activating signal transduction in the SS RBC. This stimulated adhesion requires occupancy of IAP and shear stress and is mediated by the activation of large G proteins and tyrosine kinases. Reticulocyte-enriched RBCs derived from sickle-cell disease (SCD) patients are most responsive to IAP-induced activation. These studies therefore establish peripheral SS RBCs as signaling cells that respond to a novel synergy between IAP-induced signal transduction and shear stress, suggesting new therapeutic targets in SCD.

Modelling and assessment of the impact of radiocesium and radiostrontium contamination in the Thermaikos Gulf, Greece.

A radiological model for (137)Cs and (90)Sr dispersion in the marine environment of the Thermaikos Gulf, Greece, and the river catchments draining into the Gulf, is presented. The model, developed and implemented within the MOIRA-PLUS decision support system, integrates appropriate site-specific information. The model's performance has been tested using the available empirical (137)Cs activity concentration data in abiotic and biotic components of the gulf since the Chernobyl accident. Further, this paper describes the results of a modelling exercise performed within the IAEA's EMRAS II international modelling programme to estimate the environmental sensitivity of this characteristic Mediterranean coastal marine environment following radioactive contamination. The radiation doses to humans after a single hypothetical instantaneous deposition of 1000 Bq m(-2), assuming that all of their food intake from the marine pathway comes from the local environment, were calculated. The obtained results are consistent with estimates from other models for different coastal marine environments in the frame of the above-mentioned EMRAS exercise.

Psychiatry takes to the streets: the New York City initiative for the homeless mentally ill.

The authors describe New York City's program to remove seriously mentally ill homeless people from the streets to a public hospital. They report on the 298 patients hospitalized during the first year of this program. Most of the patients were male (66%), single (77%), and from outside of New York City (79%) and claimed a history of previous psychiatric hospitalization (92%) and that they had been homeless for more than 1 year (66%). Most of the patients suffered from schizophrenia (80%) and had additional medical diagnoses (73%). Follow-up contact with the patients 2 years after initiation of the program revealed that 55% of the patients either were living in a community setting or were under institutional care.

Aquatic mosses as a monitoring tool for 137Cs contamination in streams and rivers-a field study from central southern Norway.

Mosses are frequently used as biomonitors for trace element pollution in the aquatic environment. The purpose of this study was to assess their usefulness as a tool in monitoring and in regional surveys of radioactive contamination. Specimens of the aquatic mosses, Fontinalis antipyretica and F. dalecarlica, were transplanted from non-contaminated areas to streams and rivers in the Norwegian Jotunheimen Mountains and neighbouring lowland areas that had received radioactive fallout after the Chernobyl accident. Equilibrium concentrations of 137Cs in the exposed mosses were reached after a few weeks. Two series from 20 streams in 1994 and 1996 show linear correlations between activities in water and moss samples and biomagnification ratios of 10(4) - 10(5). We conclude that mosses are better suited for monitoring purposes than water samples, because they provide values integrated over weeks while the radioactivity in surface waters can be subject to rapid variations according to hydrological events. The activity concentrations in aquatic mosses can be easily measured with good precision even when aqueous concentrations are below the limit of detection. Use of aquatic mosses also reduces the logistic problems of transporting large volumes of water, especially in areas inaccessible by road.

The sensitivity of different environments to radioactive contamination.

This paper describes modelling calculations carried out to determine the sensitivity of various rural and semi-natural environments to radionuclide contamination by (137)Cs, (90)Sr, and (131)I released during a major nuclear accident. Depositions of 1000 Bq/m(3) were assumed for each radionuclide. Four broad types of environments were considered: agricultural, forest or tundra, freshwater aquatic, and coastal marine. A number of different models were applied to each environment. The annual dose to a human population receiving most or all of its food and drinking water from a given environment was taken as a broad measure of sensitivity. The results demonstrated that environmental sensitivity was highly radionuclide specific, with (137)Cs generally giving the highest doses during the first year, especially for adults, in terrestrial and freshwater pathways. However, in coastal marine environments, (131)I and (239)Pu were more significant. Sensitivity was time dependent with doses for the first year dominating those for the 2nd and 10th years after deposition. In agricultural environments the ingestion dose from (137)Cs was higher for adults than other age groups, whereas for (90)Sr and (131)I, the ingestion dose was highest for infants. The dependence of sensitivity on social and economic factors such as individual living habits, food consumption preferences, and agricultural practices is discussed.

Prevention of posttraumatic axon sprouting by blocking collapsin response mediator protein 2-mediated neurite outgrowth and tubulin polymerization.

Epileptogenesis following traumatic brain injury (TBI) is likely due to a combination of increased excitability, disinhibition, and increased excitatory connectivity via aberrant axon sprouting. Targeting these pathways could be beneficial in the prevention and treatment of posttraumatic epilepsy. Here, we tested this possibility using the novel anticonvulsant (R)-N-benzyl 2-acetamido-3-methoxypropionamide ((R)-lacosamide [LCM]), which acts on both voltage-gated sodium channels and collapsin response mediator protein 2 (CRMP2), an axonal growth/guidance protein. LCM inhibited CRMP2-mediated neurite outgrowth, an effect phenocopied by CRMP2 knockdown. Mutation of LCM-binding sites in CRMP2 reduced the neurite inhibitory effect of LCM by ∼8-fold. LCM also reduced CRMP2-mediated tubulin polymerization. Thus, LCM selectively impairs CRMP2-mediated microtubule polymerization, which underlies its neurite outgrowth and branching. To determine whether LCM inhibits axon sprouting in vivo, LCM was injected into rats subjected to partial cortical isolation, an animal model of posttraumatic epileptogenesis that exhibits axon sprouting in cortical pyramidal neurons. Two weeks following injury, excitatory synaptic connectivity of cortical layer V pyramidal neurons was mapped using patch clamp recordings and laser scanning photostimulation of caged glutamate. In comparison with injured control animals, there was a significant decrease in the map size of excitatory synaptic connectivity in LCM-treated rats, suggesting that LCM treatment prevented enhanced excitatory synaptic connectivity due to posttraumatic axon sprouting. These findings suggest, for the first time, that LCM's mode of action involves interactions with CRMP2 to inhibit posttraumatic axon sprouting.

Pharmacodynamics, pharmacokinetics, and safety of AM211: a novel and potent antagonist of the prostaglandin D2 receptor type 2.

The prostaglandin D(2) receptor type 2 (DP2) and its ligand, PGD(2), have been implicated in the development of asthma and other inflammatory diseases. The authors evaluated the pharmacodynamics, pharmacokinetics and safety of [2'-(3-benzyl-1-ethyl-ureidomethyl)-6-methoxy-4'-trifluoromethyl-biphenyl-3-yl]-acetic acid sodium salt (AM211), a novel and potent DP2 antagonist, in healthy participants. Single and multiple doses of AM211 demonstrated dose-dependent inhibition of eosinophil shape change in blood with near-complete inhibition observed at trough after dosing 200 mg once daily for 7 days. Maximum plasma concentrations and exposures of AM211 increased in a greater-than-dose-proportional manner after single and multiple dosing. After multiple dosing, the exposures on day 7 were higher than on day 1 with accumulation ratio values ranging from 1.4 to 1.5. Mean terminal half-life values ranged from 14 to 25 hours across the dose range of 100 to 600 mg. AM211 was well tolerated at all doses in both the single- and multiple-dose cohorts. These data support additional clinical studies to evaluate AM211 in asthma and other inflammatory diseases.

Computerised Decision Support Systems for the management of freshwater radioecological emergencies: assessment of the state-of-the-art with respect to the experiences and needs of end-users.

Assessment of the environmental and radiological consequences of a nuclear accident requires the management of a great deal of data and information as well as the use of predictive models. Computerised Decision Support Systems (CDSS) are essential tools for this kind of complex assessment and for assisting experts with a rational decision process. The present work focuses on the assessment of the main features of selected state-of-the-art CDSS for off-site management of freshwater ecosystems contaminated by radionuclides. This study involved both developers and end-users of the assessed CDSS and was based on practical customisation exercises, installation and application of the decision systems. Potential end-users can benefit from the availability of several ready-to-use CDSS that allow one to run different kinds of models aimed at predicting the behaviour of radionuclides in aquatic ecosystems, evaluating doses to humans, assessing the effectiveness of different kinds of environmental management interventions and ranking these interventions, accounting for their social, economic and environmental impacts. As a result of the present assessment, the importance of CDSS "integration" became apparent: in many circumstances, different CDSS can be used as complementary tools for the decision-making process. The results of this assessment can also be useful for the future development and improvement of the CDSS.