Imaging blood-brain barrier dysfunction as a biomarker for epileptogenesis.

A biomarker that will enable the identification of patients at high-risk for developing post-injury epilepsy is critically required. Microvascular pathology and related blood-brain barrier dysfunction and neuroinflammation were shown to be associated with epileptogenesis after injury. Here we used prospective, longitudinal magnetic resonance imaging to quantitatively follow blood-brain barrier pathology in rats following status epilepticus, late electrocorticography to identify epileptic animals and post-mortem immunohistochemistry to confirm blood-brain barrier dysfunction and neuroinflammation. Finally, to test the pharmacodynamic relevance of the proposed biomarker, two anti-epileptogenic interventions were used; isoflurane anaesthesia and losartan. Our results show that early blood-brain barrier pathology in the piriform network is a sensitive and specific predictor (area under the curve of 0.96, P < 0.0001) for epilepsy, while diffused pathology is associated with a lower risk. Early treatments with either isoflurane anaesthesia or losartan prevented early microvascular damage and late epilepsy. We suggest quantitative assessment of blood-brain barrier pathology as a clinically relevant predictive, diagnostic and pharmaco!dynamics biomarker for acquired epilepsy.

Using the skin protective lotion IB1 as a substitute for chemical protective gloves.

We aimed to evaluate the performance of medical personnel in using the IB1 topical protective lotion on their hands and wrists together with standard disposable medical gloves, compared to standard-issued medical chemical protective gloves. This randomized cross-over study included 144 medical personnel. Primary endpoints were time-to-completion of autoinjection; success rate, number of attempts, and time-to-achieve successful endotracheal intubation; time-to-achieve satisfactory tube fixation; time-to-draw and inject the content of an ampoule; and the total time-to-perform all medical procedures. Secondary endpoints included the subjective assessment of convenience to perform these four procedures with each protective measure. Mean time was significantly shorter using IB1 compared to chemical protective gloves for tube fixation, ampoule drawing, and the total time-to-perform all procedures (58.6±22.7 seconds vs. 71.7±29.7; 31.5±21.8 vs. 38.2±19.4; 137.4±56.1 vs. 162.5±63.6, respectively; P<.001 for all). For all medical procedures, the use of IB1 was reported as significantly more convenient than the use of chemical protective gloves (P<.001 for all comparisons). IB1 with standard medical gloves significantly shorten the time-to-perform medical procedures requiring fine motor dexterities and is subjectively more convenient than chemical protective gloves. IB1 should be considered as an appropriate alternative for medical teams in a chemical event.

Lessons learned from the Syrian sarin attack: evaluation of a clinical syndrome through social media.

On the night of 21 August 2013, sarin was dispersed in the eastern outskirts of Damascus, killing 1400 civilians and severely affecting thousands more. This article aims to delineate the clinical presentation and management of a mass casualty event caused by a nerve agent as shown in the social media. Authors searched YouTube for videos uploaded of this attack and identified 210 videos. Of these, 67 met inclusion criteria and were evaluated in the final analysis.These videos displayed 130 casualties; 119 (91.5%) of which were defined as moderately injured or worse. The most common clinical signs were dyspnea (53.0%), diaphoresis (48.5%), and loss of consciousness (40.7%). Important findings included a severe shortage of supporting measures and lack of antidotal autoinjectors. Decontamination, documented in 25% of the videos, was done in an inefficient manner. Protective gear was not noticed, except for sporadic use of latex gloves and surgical masks.This is believed to be the first time that social media was used to evaluate clinical data and management protocols to better prepare against future possible events.

Intubation using the gum-elastic bougie while wearing personal protective equipment.

OBJECTIVE: To determine whether application of a gum-elastic bougie (GEB), a visual stylet used to improve success rates of difficult intubations, reduces the time, and number of attempts to achieve successful intubation while wearing personal protective equipment (PPE). DESIGN: A randomized cross-over study comparing orotracheal intubations performed on an AirMan® Mannequin, using either a semirigid stylet or a GEB, while wearing an active hood with a charcoal impregnated suit and butyl rubber gloves. SETTING: Simulation training field of the Israel Defense Force Medical Corps. PARTICIPANTS: 27 military physicians and 23 paramedics (PMs). INTERVENTIONS: Comparing intubation with and without using the GEB while wearing PPE. MAIN OUTCOME MEASURE(S): Airway (AW) control was considered successful if the "lungs" of the mannequin ex-panded during bag ventilation. Three unsuccessful attempts or a procedure exceeding 60 seconds were regarded as a failure. Correlations between parameters of self-assessment of skills and successful intubation were also determined. RESULTS: With the GEB, success rate was lower (82 percent versus 100 percent, p = 0.002), more attempts were needed (1.4 ± 0.7 versus 1.0 ± 0.2, p = 0.005) and time-to-achieve AW control was longer (43.6 ± 14.6 sec-onds versus 23.1 ± 10.5 seconds, P < 0.001) than without it. Participants with high self-assessment of GEB-assisted AW management skills needed less attempts to perform successful intubation with GEB than participants with low self-assessment (1.0 ± 0.0 versus 1.4 ± 0.8, p = 0.001), but not less time to achieve it. CONCLUSIONS: While donning PPE, the use of GEB (versus semirigid stylets) did not reduce the time or the number of attempts necessary to achieve successful intubation.

A comparison between 68Ga-labeled prostate-specific membrane antigen-PET/CT and multiparametric MRI for excluding regional metastases prior to radical prostatectomy.

OBJECTIVES: To compare the ability of 68Ga -PSMA PET/CT (PSMA PET/CT) and multiparametric MRI (mpMRI) to exclude lymph node invasion (LNI) in patients who undergo radical prostatectomy (RP). MATERIALS AND METHODS: A multicenter cohort of patients who underwent PSMA PET/CT and pelvic mpMRI prior to RP with pelvic lymph node dissection (PLND) was analyzed. Increased Ga68-PSMA uptake on PET/CT and enlarged (> 10 mm) or abnormal lymph nodes on mpMRI were considered positive findings. The final surgical pathology served as the standard of reference. The negative predictive value (NPV) was calculated for each modality separately, as well as the combined value. RESULTS: Included were 89 patients with D'Amico intermediate (45%) or high-risk (55%) prostate cancer. The median number of extracted LN was 9 (IQR 6-14). LNI was found in 12 (13.5%) patients. The NPV of mpMRI, PSMA PET/CT, and the two tests combined were 87%, 89%, and 90%, in the entire cohort, 95%, 97%, and 97% in patients with intermediate-risk disease, and 80%, 82%, and 83% in patients with high-risk disease, respectively. The median diameter of LN missed by both imaging and the median intranodal tumor diameter was 5.5 (IQR 3-10) mm and 1 (IQR 1-3) mm, respectively. CONCLUSIONS: PSMA PET/CT and mpMRI demonstrated similar performance in excluding pelvic LNI with NPV of approximately 90%. The combination of both tests does not improve NPV significantly. Therefore, even in the era of advanced imaging, PLND is still recommended for accurate staging, especially in the high-risk population.

Resveratrol fails to provide prophylactic protection in a rat model of organophosphate poisoning.

BACKGROUND: Paraoxonase-1, an organophosphorous-hydrolyzing enzyme, was shown to provide protection against organophosphates poisoning in vivo. In vitro findings suggest that the phytoalexin resveratrol can elevate paraoxonase-1 levels and thus may provide protection against organophosphate poisoning. This study was conducted to evaluate the effect of prolonged resveratrol intake on paraoxonase-1 levels in rats, and its role as a potential prophylactic treatment in organophosphate poisoning. METHODS: 30 adult male albino Sprague-Dawley rats were randomly assigned into three groups: rats receiving no resveratrol (Control group, n = 10), rats treated once daily with oral gavage of ethanol only (Sham group, n = 6), and rats treated once daily with oral gavage of resveratrol (50 mg/kg) (Study group, n = 14). Following 2 weeks of feeding, all rats were exposed to 1.4LD50 paraoxon (450 mg/kg, intramuscular; 0.5 ml/kg) and monitored for severity of clinical signs and mortality. Paraoxonase-1 activity level was recorded in the beginning of the study and 2 weeks later, just before exposure to paraoxon. RESULTS: We found a significant decrease in paraoxonase-1 activity levels in all groups compared to baseline levels (p = 0.05), but no significant difference was observed between the study group and the controls (p = 0.7). Following exposure to paraoxon, all animals suffered from severe convulsions and died within minutes. CONCLUSIONS: Following resveratrol intake in rats, paraoxonase-1 activity levels decreased. We found no beneficial effects in using resveratrol as a prophylactic medical countermeasure.

Early brain magnetic resonance imaging can predict short and long-term outcomes after organophosphate poisoning in a rat model.

INTRODUCTION: Magnetic resonance (MR) imaging is a sensitive modality for demonstrating in vivo alterations in brain structure and function after acute organophosphate (OP) poisoning. The goals of this study were to explore early imaging findings in organophosphate-poisoned animals, to assess the efficacy of centrally acting antidotes and to find whether early MR findings can predict post-poisoning cognitive dysfunction. METHODS: Sprague-Dawley rats were poisoned with the agricultural OP paraoxon and were treated with immediate atropine and obidoxime (ATOX) to reduce acute mortality caused by peripheral inhibition of acetylcholinesterase. Animals were randomly divided into three groups based on the protocol of centrally acting antidotal treatment: group 1 - no central antidotal treatment (n=10); group 2 - treated with midazolam (MID) at 30 min after poisoning (n=9), group 3 - treated with a combination of MID and scopolamine (SCOP) at 30 min after poisoning (n=9) and controls (n=6). Each animal had a brain MR examination 3 and 24 h after poisoning. Each MR examination included the acquisition of a T2 map and a single-voxel (1)H MR spectroscopy (localized on the thalami, to measure total creatine [Cr], N-acetyl-aspartate [NAA] and cholines [Cho] levels). Eleven days after poisoning each animal underwent a Morris water maze to assess hippocampal learning. Eighteen days after poisoning, animals were euthanized, and their brains were dissected, fixed and processed for histology. RESULTS: All paraoxon poisoned animals developed generalized convulsions, starting within a few minutes following paraoxon injection. Brain edema was maximal on MR imaging 3 h after poisoning. Both MID and MID+SCOP prevented most of the cortical edema, with equivalent efficacy. Brain metabolic dysfunction, manifested as decreased NAA/Cr, appeared in all poisoned animals as early as 3h after exposure (1.1 ± 0.07 and 1.42 ± 0.05 in ATOX and control groups, respectively) and remained lower compared to non-poisoned animals even 24h after poisoning. MID and MID+SCOP prevented much of the 3h NAA/Cr decrease (1.22 ± 0.05 and 1.32 ± 0.1, respectively). Significant correlations were found between imaging findings (brain edema and spectroscopic changes) and clinical outcomes (poor learning, weight loss and pathological score) with correlation coefficients of 0.4-0.75 (p<0.05). CONCLUSIONS: MR imaging is a sensitive modality to explore organophosphate-induced brain damage. Delayed treatment with midazolam with or without scopolamine provides only transient neuroprotection with some advantage in adding scopolamine. Early imaging findings were found to correlate with clinical consequences of organophosphate poisoning and could be potentially used in the future to predict long-term prognosis of poisoned casualties.

Measles virus antigens in breast cancer.

INTRODUCTION: Breast cancer (BC) is the most common cancer in women in Western countries, showing a bimodal age distribution with peaks at 50 and 70 years. Multiple factors are encountered in the etiology of BC, including hereditary and hormonal causes. A few viruses, including MMTV, EBV and HPV have been reported to be associated with BC. This group previously described the presence of the measles virus (MV) in biopsies of patients with Hodgkin's lymphoma. The present study explored MV antigens in BC patients. PATIENTS AND METHODS: A total of 131 patients with invasive BC diagnosed during the years 1998-2005 were studied using immunohistochemistry (IHC) for the presence of MV antigens, hemagglutinin and nucleoprotein. Clinicopathological parameters included age, stage, histological grade and the expression of estrogen and progesterone receptors, HER2/neu, p53, and Ki67. RESULTS: Hormone receptors and HER2/neu were positive in 54% and 18% of the tumors, respectively. Both MV antigens were detected in 64% of the tumors. All biopsies containing a DCIS component showed MV in DCIS in addition to invasive BC. In univariate analysis, MV correlated with estrogen receptor (p=0.018), low Ki67 index (<40%, p=0.029), low or intermediate grade (p=0.037), age under 50 years (p=0.039), progesterone receptor (p=0.043) and overexpression of p53 (p=0.049). In multivariate analysis, only grade (p=0.011), p53 (p=0.03) and age (p=0.041) remained associated with MV. CONCLUSION: This study provides evidence for the presence of MV antigens in a relatively large proportion of BC patients. MV was associated with younger age, lower histological grade and overexpression of p53, suggesting that it may play a role in the development of BC.