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Objectives: Postconcussion symptoms (PCS) are a common complication of mild traumatic brain injury (TBI). Currently, there is no validated clinically available method to reliably predict at the time of injury who will subsequently develop PCS. The purpose of this study was to determine if PCS following mild TBI can be predicted during the initial presentation to an emergency department (ED) using a novel robotic-assisted assessment of neurologic function., Methods: All patients presenting to an urban ED with a chief complaint of head injury within the preceding 24 hours were screened for inclusion from March 2013 to April 2014. The enrollment criteria were as follows: 1) age of 18 years or greater, 2) ability and willingness to provide written informed consent, 3) blunt head trauma and clinical diagnosis of isolated mild TBI by the treating physician, and 4) blood alcohol level of <100 mg/dL. Eligible mild TBI patients were enrolled and their neuromotor function was assessed in the ED using a battery of five tests that cover a range of proprioceptive, visuomotor, visuospatial, and executive function performance metrics. At 3 weeks postinjury, participants were contacted via telephone to complete the Rivermead Post-Concussion Symptoms Questionnaire to assess the presence of significant PCS., Results: A total of 66 mild TBI patients were enrolled in the study with 42 of them completing both the ED assessment and the follow-up; 40 patients were included in the analyses. The area under the receiver operating characteristic curve (AUC) for the entire test battery was 0.72 (95% confidence interval [CI] = 0.54 to 0.90). The AUC for tests that primarily measure visuomotor and proprioceptive performance were 0.80 (95% CI = 0.65 to 0.95) and 0.71 (95% CI = 0.53 to 0.89), respectively., Conclusions: The robotic-assisted test battery has the ability to discriminate between subjects who developed PCS and those who did not. Additionally, poor visuomotor and proprioceptive performance were most strongly associated with subsequent PCS., (© 2016 by the Society for Academic Emergency Medicine.)

Background: Incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing in complicated skin and skin structure infection (cSSSI) presenting to emergency departments (EDs). Treatment is heterogeneous and can require inpatient admission to an observation unit (OU). Vancomycin is commonly used in the OU for treatment, but increasing MRSA resistance to vancomycin suggests the need for alternatives. Daptomycin is an alternative but it is not known how it compares with vancomycin., Objective: This study tested the hypothesis that daptomycin is noninferior to vancomycin for the treatment of cSSSI in an OU, using a relative risk (RR) of 1.3 as the noninferiority limit., Methods: Subjects admitted to an ED-based OU with a diagnosis of cSSSI were eligible. Consenting subjects were randomized 1:1 to intravenous (i.v.) vancomycin at 15 mg/kg dosing every 12 h or i.v. daptomycin at 4 mg/kg once. Subjects were followed until they met objective criteria for discharge home or hospital admission. Discharged patients were prescribed 10-14 days of oral cephalexin and trimethoprim-sulfamethoxazole, or clindamycin if allergic to either of these medications. The primary endpoint was meeting objective discharge criteria with no change in antibiotic therapy or return to the ED for the same cellulitis within 30 days of OU discharge., Results: There were 100 patients enrolled. RR for satisfying the endpoint was 1.07 (95% confidence interval 0.58-1.98) for daptomycin compared with vancomycin. Hospital admission rates were 36% and 32% for daptomycin and vancomycin treatment, respectively., Conclusion: Daptomycin was not inferior to vancomycin in the treatment of cSSSI in an OU., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Unlabelled: The objective of this paper is to demonstrate the effective deployment of a robotic assessment tool for the evaluation of mild traumatic brain injury (mTBI) patients in a busy, resource-constrained, urban emergency department (ED)., Methods: Functional integration of new robotic technology for research in the ED presented several obstacles that required a multidisciplinary approach, including participation from electrical and computer engineers, emergency medicine clinicians, and clinical operations staff of the hospital. Our team addressed many challenges in deployment of this advanced technology including: 1) adapting the investigational device for the unique clinical environment; 2) acquisition and maintenance of appropriate testing space for point-of-care assessment; and 3) dedicated technical support and upkeep of the device. Upon successful placement of the robotic device in the ED, the clinical study required screening of all patients presenting to the ED with complaints of head injury. Eligible patients were enrolled and tested using a robot-assisted test battery. Three weeks after the injury, patients were contacted to complete follow-up assessments., Results: Adapting the existing technology to meet anticipated physical constraints of the ED was performed by engineering a mobile platform. Due to the large footprint of the device, it was frequently moved before ultimately being fully integrated into the ED. Over 14 months, 1423 patients were screened. Twenty-eight patients could not be enrolled because the device was unavailable due to operations limitations. Technical problems with the device resulted in failure to include 20 patients. A total of 66 mTBI patients were enrolled and 42 of them completed both robot-assisted testing and follow-up assessment. Successful completion of screening and enrollment demonstrated that the challenges associated with integration of investigational devices into the ED can be effectively addressed through a collaborative patient-oriented research model., Conclusion: Effective deployment and use of new robotic technology for research in an urban academic ED required significant planning, coordination, and collaboration with key personnel from multiple disciplines. Clinical Impact: A pilot clinical study on mTBI patients using the robotic device provided useful data without disrupting the ED workflow. Integration of this technology into the ED serves as an important step toward pursing active clinical research in an acute care setting.

Plasmin, a direct fibrinolytic, shows a significantly superior hemostatic safety profile compared to recombinant tissue plasminogen activator (rtPA), the only FDA-approved thrombolytic for the treatment of acute ischemic stroke. The improved safety of plasmin is attributed to the rapid inhibition of free plasmin by endogenous plasmin inhibitors present in very high concentrations (1 μM). However, this rapid inhibition prevents the intravenous (IV) administration of plasmin. In emergency situations, catheter-based local administration is not practical. There is a need for an alternative technique for IV administration of plasmin. A possible solution is the encapsulation of plasmin in echogenic liposomes (ELIP) for protection from inhibitors until ultrasound (US)-triggered release at the clot site. ELIP are bilayer phospholipid vesicles with encapsulated gas microbubbles. US induces oscillation and collapse of the gas bubbles, which facilitates ELIP rupture and delivery of the encapsulated contents. Plasmin-loaded ELIP (PELIP) were manufactured and characterized for size, gas and drug encapsulations, and in vitro thrombolytic efficacy using a human whole blood clot model. Clots were exposed to PELIP with and without exposure to US (center frequency 120 kHz, pulse repetition frequency 1667 Hz, peak-to-peak pressure of 0.35 MPa, 50 % duty cycle). Thrombolytic efficacy was calculated by measuring the change in clot width over a 30-min treatment period using an edge detection MATLAB program. The mean clot lysis obtained with PELIP in the presence of US exposure was 31 % higher than that obtained without US exposure and 15 % higher than that obtained with rtPA treatment (p < 0.05).The enhanced clot lysis is attributed to the US-mediated release of plasmin from the liposomes.

Background: Rheumatic heart disease (RHD) remains a major public health problem worldwide. Although early diagnosis by echocardiography may potentially play a key role in developing active surveillance, systematic evaluation of simple approaches in resource poor settings are needed., Methods and Results: We prospectively compared focused cardiac ultrasound (FCU) to a reference approach for RHD screening in a school children population. FCU included (1) the use of a pocket-sized echocardiography machine, (2) nonexpert staff (2 nurses with specific training), and (3) a simplified set of echocardiographic criteria. The reference approach used standardized echocardiographic examination, reviewed by an expert cardiologist, according to 2012 World Heart Federation criteria. Among the 6 different echocardiographic criteria, first tested in a preliminary phase, mitral regurgitation jet length≥2 cm or any aortic regurgitation was considered best suited to be FCU criteria. Of the 1217 subjects enrolled (mean, 9.6±1 years; 49.6% male), 49 (4%) were diagnosed with RHD by the reference approach. The sensitivity of FCU for the detection of RHD was 83.7% (95% confidence interval, 73.3-94.0) for nurse A and 77.6% (95% confidence interval, 65.9-89.2) for nurse B. FCU yielded a specificity of 90.9% (95% confidence interval, 89.3-92.6) and 92.0% (95% confidence interval, 90.4-93.5) according to users. Percentage of agreement among nurses was 91.4%., Conclusions: FCU by nonexperts using pocket devices seems feasible and yields acceptable sensitivity and specificity for RHD detection when compared with the state-of-the-art approach, thereby opening new perspectives for mass screening for RHD in low-resource settings., (© 2015 American Heart Association, Inc.)

Post-Concussion Syndrome (PCS) is a common sequelae of mild Traumatic Brain Injury (mTBI). Currently, there is no reliable test to determine which patients will develop PCS following an mTBI. As a result, clinicians are challenged to identify patients at high risk for subsequent PCS. Hence, there is a need to develop an objective test that can guide clinical risk stratification and predict the likelihood of PCS at the initial point of care in an Emergency Department (ED). This paper presents the results of robotic-assisted neurologic testing completed on mTBI patients in the ED and its ability to predict PCS at 3 weeks post-injury. Preliminary results show that abnormal proprioception, as measured using robotic testing is associated with higher risk of developing PCS following mTBI. In this pilot study, proprioceptive measures obtained through robotic testing had a 77% specificity (95CI: 46%-94%) and a 64% sensitivity (95CI: 41%-82%).

Objectives: Recombinant tissue plasminogen activator (rt-PA) is a lytic medication widely used in the emergency department to treat acute thrombotic disorders such as ischemic stroke and myocardial infarction. It is known in the clinical use of this drug that it can be less effective in approximately 25% of individuals receiving such treatment. However, there are no data on the variation of lytic efficacy of rt-PA in decreasing individuals' clot size over time. In this study, in vitro lytic efficacy was determined by measuring the decrease in clot diameter after 30 minutes of drug exposure. The authors sought to explore whether there are individuals who do not respond to this lytic therapy and to estimate the rate of nonresponse., Methods: Human whole blood clots were made from blood drawn from 22 adult volunteers. The only exclusion criterion was the use of aspirin within 72 hours of the blood draw. Blood clots were allowed to spontaneously form at room temperature and were then incubated at 37°C for 3 hours to ensure complete clot retraction. Sample clots from the same individuals were then exposed to human fresh-frozen plasma (hFFP) control or rt-PA in hFFP (rt-PA) at a concentration of 3.15 μg/mL. All clots were exposed at 37°C for 30 minutes, and clot diameter was measured as a function of time, using a microscopic imaging technique. The fractional clot loss (FCL), which is the percentage decrease in clot diameter at 30 minutes, was used as a measure of lytic efficacy., Results: Means with standard deviation (SD) FCL values were 8.6% (±3.0%) for control and 20.6% (±9.3%) for rt-PA-treated clots. The mean (±SD) difference in FCL values was 12.0% (±8.8%) and was significant (p < 0.05, paired t-test). Five of the 22 subjects (23%) were "rt-PA nonresponders," in that their FCL (rt-PA) values fell within that of the FCL control values., Conclusions: Overall, rt-PA does not produce clot lysis in vitro in clots from a substantial minority of the population, likely due to individual variations in clot composition and structure., (© 2013 by the Society for Academic Emergency Medicine.)

Background: Incidence of acute rheumatic fever (ARF) and prevalence of rheumatic heart disease (RHD) in the Pacific region, including New Caledonia, are amongst the highest in the world. The main priority of long-term management of ARF or RHD is to ensure secondary prophylaxis is adhered to. The objectives of this study were to evaluate rates of adherence in people receiving antibiotic prophylaxis by intramuscular injections of penicillin in Lifou and to determine the factors associated with a poor adherence in this population., Methods: We conducted a retrospective cohort study and we included 70 patients receiving injections of antibiotic prophylaxis to prevent ARF recurrence on the island of Lifou. Patients were classified as "good-adherent" when the rate of adherence was ≥80% of the expected injections and as "poor-adherent" when it was <80%. Statistical analysis to identify factors associated with adherence was performed using a multivariate logistic regression model., Results: Our study showed that 46% of patients from Lifou receiving antibiotic prophylaxis for ARF or RHD had a rate of adherence <80% and were therefore at high risk of recurrence of ARF. Three independent factors were protective against poor adherence: a household with more than five people (odds ratio, 0.25; 95% confidence interval [CI], 0.08 to 0.75), a previous medical history of symptomatic ARF (odds ratio, 0.20; 95% CI, 0.04 to 0.98) and an adequate healthcare coverage (odds ratio, 0.21; 95% CI 0.06 to 0.72)., Conclusions: To improve adherence to secondary prophylaxis in Lifou, we therefore propose the following recommendations arising from the results of this study: i) identifying patients receiving antibiotic prophylaxis without medical history of ARF to strengthen their therapeutic education and ii) improving the medical coverage in patients with ARF or RHD. We also recommend that the nurse designated for the ARF prevention program in Lifou coordinate an active recall system based on an updated local register. But the key point to improve adherence among Melanesian patients is probably to give appropriate information regarding the disease and the treatment, taking into account the Melanesian perceptions of the disease.

Aim: Despite the well-documented burden of rheumatic heart disease (RHD) in several Pacific countries, the disease is poorly understood in New Caledonia. The aim of this study was to assess the prevalence of RHD detected by echocardiographic screening in school children., Methods: An annual RHD screening programme is conducted by the Health and Social Agency of New Caledonia for school-aged children in their fourth year of primary school. For the purpose of this study, we used data collected during this echocardiographic screening between 2008 and 2010., Results: Of 12,728 children screened, 50.2% were male and the mean age was 9.6 ± 0.6 years. Between 2008 and 2010, 114 children had RHD, corresponding to a prevalence of 8.9 cases per 1000 (95% confidence interval (CI) (7.3-10.6)). Prevalence of RHD was higher on the main island outside Greater Noumea (13.7 per 1000; 95% CI (9.8-17.5)) and in the outlying island groups (14.6 per 1000; 95% CI (8.4-20.9)) than in Greater Noumea (5.8 per 1000; 95% CI (4.1-7.5)). RHD was more prevalent in Melanesian children (13.5 per 1000; 95% CI (10.9-16.1)) than in European (1.8 per 1000; 95% CI (0.4-3.1))., Conclusion: This study documented a high prevalence of RHD in New Caledonia, particularly in districts located outside Noumea and in children of Melanesian heritage. These results uncover a hitherto unknown burden of disease in New Caledonia and underline the importance of delivering secondary prophylaxis to reduce the prevalence of RHD., (© 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

The potential for hypothermia as a neuroprotectant during stroke has led to its increase in clinical use. At the same time, combination pharmaceutical therapies for ischemic stroke using recombinant tissue plasminogen activator (rt-PA), and GP IIb-IIIa inhibitors, such as Eptifibatide (Epf ), are under study. However, there is little data on how the reactions triggered by these agents are impacted by temperature. Here, clot lysis during exposure to the combination of rt-PA and Epf is measured in an in vitro human clot model at hypothermic temperatures. The hypothesis is that lytic efficacy of rt-PA and Epf decreases with decreasing temperature. Whole blood clots from 31 volunteers were exposed to rt-PA (0.5 μg/mL) and Epf (0.63 μg/mL) in human fresh-frozen plasma (rt-PA+Epf ), rt-PA alone in plasma (rt-PA Alone), or to plasma alone (Control), at temperatures from 30°C to 37°C, for 30 minutes. Clot lysis was measured using a microscopic imaging technique; the mean fractional clot loss (FCL) at 30 minutes was used to determine lytic efficacy. Temperature had a significant impact on FCL in clots exposed to rt-PA+Epf, with the FCL being lower at 30°C to 36°C than at 37°C. The FCL remained significantly higher for rt-PA+Epf–treated clots than Controls regardless of temperature, with the exception of measurements made at 30°C when no significant differences in the FCL were observed between groups. The use of hypothermia as a neuroprotectant may negatively impact the therapeutic benefit of thrombolytic agents.

Incidence of intra-cranial hemorrhage linked to treatment of ischemic stroke with recombinant tissue plasminogen activator (rt-PA) has led to interest in adjuvant therapies such as ultrasound (US) or plasminogen, to enhance rt-PA efficacy and improve patient safety. High-frequency US (∼MHz) such as 2-MHz transcranial Doppler (TCD) has demonstrated increased recanalization in situ. Low-frequency US (∼kHz) enhanced thrombolysis (UET) has demonstrated higher lytic capabilities but has been associated with incidence of intracerebral hemorrhage in some clinical trials. In vitro studies using plasminogen have shown enhancement of lysis. This study compared rt-PA-induced lysis using adjuvant therapies, with 120-kHz or 2-MHz pulsed US, or plasminogen, in an in vitro human whole blood clot model. Blood was drawn from 30 subjects after local institutional approval. Clots were exposed to rt-PA at concentrations of 0 to 3.15 μg/ml. Clots were exposed to rt-PA alone (rt-PA) or in combination with plasminogen (Plg), 120-kHz US (120-kHz), or 2-MHz US (2-MHz). Thrombolytic efficacy was determined by assessing the percent fractional clot loss (FCL) at 30 minutes using microscopic imaging. There was no enhancement of lysis for combination therapy with [rt-PA]=0 μg/ml. Adding rt- PA increased lysis for all groups. As [rt-PA] increased, lysis tended to increase for 120-kHz and Plg (FCL: from 50% to 70%, 120-kHz; 65% to 83%, Plg) but not for 2-MHz (58% to 52%). Lytic efficacy in combination therapy depends on rt- PA concentration and the adjuvant therapy type. For non-zero rt-PA concentrations, all combination therapies produced more lysis than rt-PA alone.

Introduction: Recombinant tissue plasminogen activator (rt-PA) is the only FDA approved lytic therapy for acute ischemic stroke. However, there can be complications such as intra-cerebral hemorrhage. This has led to interest in adjuncts such as GP IIb-IIIa inhibitors. However, there is little data on combined therapies. Here, we measure clot lysis for rt-PA and eptifibatide in an in vitro human clot model, and determine the drug concentrations maximizing lysis. A pharmacokinetic model is used to compare drug concentrations expected in clinical trials with those used here. The hypothesis is that there is a range of rt-PA and eptifibatide concentrations that maximize in vitro clot lysis., Materials and Methods: Whole blood clots were made from blood obtained from 28 volunteers, after appropriate institutional approval. Sample clots were exposed to rt-PA and eptifibatide in human fresh-frozen plasma; rt-PA concentrations were 0, 0.5, 1, and 3.15 μg/ml, and eptifibatide concentrations were 0, 0.63, 1.05, 1.26 and 2.31 μg/ml. All exposures were for 30 minutes at 37 C. Clot width was measured using a microscopic imaging technique and mean fractional clot loss (FCL) at 30 minutes was used to determine lytic efficacy. On average, 28 clots (range: 6-148) from 6 subjects (3-24) were used in each group., Results and Conclusions: FCL for control clots was 14% (95% Confidence Interval: 13-15%). FCL was 58% (55-61%) for clots exposed to both drugs at all concentrations, except those at an rt-PA concentration of 3.15 μg/ml, and eptifibatide concentrations of 1.26 μg/ml (Epf) or 2.31 μg/ml. Here, FCL was 43% (36-51) and 35% (32-38) respectively. FCL is maximized at moderate rt-PA and eptifibatide concentration; these values may approximate the average concentrations used in some rt-PA and eptifibatide treatments., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background and Purpose: Currently, the only FDA-approved therapy for acute ischemic stroke is the administration of recombinant tissue plasminogen activator (tPA). Echogenic liposomes (ELIP), phospholipid vesicles filled with gas and fluid, can be manufactured to incorporate tPA. Also, transcranial ultrasound-enhanced thrombolysis can increase the recanalization rate in stroke patients. However, there is little data on lytic efficacy of combining ultrasound, echogenic liposomes, and tPA treatment. In this study, we measure the effects of pulsed 120-kHz ultrasound on the lytic efficacy of tPA and tPA-incorporating ELIP (t-ELIP) in an in-vitro human clot model. It is hypothesized that t-ELIP exhibits similar lytic efficacy to that of rt-PA., Methods: Blood was drawn from 22 subjects after IRB approval. Clots were made in 20-microL pipettes, and placed in a water tank for microscopic visualization during ultrasound and drug treatment. Clots were exposed to combinations of [tPA]=3.15 microg/ml, [t-ELIP]=3.15 microg/ml, and 120-kHz ultrasound for 30 minutes at 37 degrees C in human plasma. At least 12 clots were used for each treatment. Clot lysis over time was imaged and clot diameter was measured over time, using previously developed imaging analysis algorithms. The fractional clot loss (FCL), which is the decrease in mean clot width at the end of lytic treatment, was used as a measure of lytic efficacy for the various treatment regimens., Results: The fractional clot loss FCL was 31% (95% CI: 26-37%) and 71% (56-86%) for clots exposed to tPA alone or tPA with 120 kHz ultrasound. Similarly, FCL was 48% (31-64%) and 89% (76-100%) for clots exposed to t-ELIP without or with ultrasound., Conclusions: The lytic efficacy of tPA containing echogenic liposomes is comparable to that of tPA alone. The addition of 120 kHz ultrasound significantly enhanced lytic treatment efficacy for both tPA and t-ELIP. Liposomes loaded with tPA may be a useful adjunct in lytic treatment with tPA.

Background: Recombinant tissue plasminogen activator (tPA) is a thrombolytic widely used clinically in the treatment of acute thrombotic disease such as ischemic stroke, myocardial infarction, and deep venous thrombosis. This has led to much interest in tPA based lytic therapies leading to laboratory based in-vitro and in-vivo investigations using this drug. However, tPA reconstituted in solution exhibits full activity for only 6-8 hours, according to the manufacturer. Therefore, methods to store reconstituted tPA for long durations while maintaining activity would be of assistance to laboratories using this enzyme., Findings: In this work, the enzymatic activity of tPA stored at -80 C over time was measured, using an ELISA technique that measured the amount of active tPA bound to plasminogen activator inhibitor 1 (PAI-1) in a given sample. Sample of tPA solution mixed to a concentration of 1 (mg/ml) were stored in cryogenic vials at -80 C for up to 7 years. For a given sample, aliquots were assayed for tPA activity, and compared with a tPA standard to determine relative enzymatic activity. Results are reported as means with standard errors, and 12 measurements were performed for each sample age., Conclusion: There was no decrease in tPA activity for samples stored up to 7 years. Such cryogenic storage is a viable method for the preservation of tPA solution for laboratory investigations of tPA-based lytic therapies.

Introduction: Fibrinolytics such as recombinant tissue plasminogen activator (rt-PA) are used to treat thrombotic disease such as acute myocardial infarction (AMI) and ischemic stroke. Interest in increasing efficacy and reducing side effects has led to the study of adjuncts such as GP IIb-IIIa inhibitors and ultrasound (US) enhanced thrombolysis. Currently, GP IIb-IIIa inhibitor and fibrinolytic treatment are often used in AMI, and are under investigation for stroke treatment. However, little is known of the efficacy of combined GP IIb-IIIa inhibitor, fibrinolytic and ultrasound treatment. We measure the lytic efficacy of rt-PA, eptifibatide (Epf) and 120 kHz ultrasound treatment in an in-vitro human clot model., Materials and Methods: Blood was drawn from 15 subjects after IRB approval. Clots were made in 20 microL pipettes, and placed in a water tank for microscopic visualization during lytic treatment. Clots were exposed to control, rt-PA (rt-PA), eptifibatide (Epf), or rt-PA+eptifibatide (rt-PA + Epf), with (+US) or without (-US) ultrasound for 30 minutes at 37 degrees C in human plasma. Clot lysis was measured over time, using a microscopic imaging technique. The fractional clot loss (FCL) and initial lytic rate (LR) were used to quantify lytic efficacy., Results and Conclusions: LR values for (- US) treated clots were 0.8+/-0.1(control), 1.8+/-0.3 (Epf), 1.5+/-0.2 (rt-PA), and 1.3+/-0.4 (rt-PA + Epf) (% clot width/minute) respectively. In comparison, the (+ US) group exhibited LR values of 1.6+/-0.2 (control), 4.3+/-0.4 (Epf), 6.3+/-0.4 (rt-PA), and 4.6+/-0.6 (rt-PA + Epf). For (- US) treated clots, FCL was 6.0+/-0.8 (control), 9.2+/-2.5 (Epf), 15.6+/-1.7 (rt-PA), and 28.0+/-2.2% (rt-PA + Epf) respectively. FCL for (+ US) clots was 13.5+/-2.4 (control), 20.7+/-6.4 (Epf), 44.4+/-3.6 (rt-PA) and 30.3+/-3.6% (rt-PA + Epf) respectively. Although the addition of eptifibatide enhances the in-vitro lytic efficacy of rt-PA in the absence of ultrasound, the efficacy of ultrasound and rt-PA is greater than that of combined ultrasound, rt-PA and eptifibatide exposure.

It has been known for some time that the application of ultrasound can enhance the efficacy of thrombolytic medications such as recombinant tissue plasminogen activator (rt-PA). Potential clinical applications of this ultrasound-enhanced thrombolysis (UET) include the treatment of myocardial infarction, acute ischemic stroke, deep venous thrombosis and other thrombotic disorders. It may be possible to reduce the dose of rt-PA while maintaining lytic efficacy; however there is little data on the rt-PA concentration dependence of UET. In this work, the rt-PA concentration dependence of clot lysis resulting from 120 kHz UET exposure was measured in an in vitro human clot model. Clots were exposed to rt-PA for 30 min, with (UET treated) or without 120 kHz ultrasound (rt-PA treated) at 37 degrees C, and the clot width measured as a function of time. The rt-PA concentration ranged from 0-10 microg/mL. The initial lytic rate for the UET-treated group was greater than that of the rt-PA group at almost all rt-PA concentrations, and exhibited a maximum over concentration values of 1-3 microg/mL.

The release of a strawberry aroma from different composite gels taken as models of fruit preparations and from a sucrose solution was investigated. The composition of the model systems differed with regard to the gelling agent, either pectin or carrageenan, and to the rigidity of the gel. With the use of atmospheric pressure chemical ionization-mass spectrometry, the release profiles of the aroma compounds were determined under stirring. At the same time, purge and trap measurements were performed to determine the release profiles of the aroma compounds without stirring. The comparison of the patterns obtained using these two complementary methods made it possible to determine how the structure of the matrix, the mechanical treatment, and the properties of the aroma compound affect aroma release. A far greater proportion of the aroma compounds was retained in the fruit preparation systems than in the sucrose solution. The different release profiles could be interpreted in terms of the volatility of the aroma compounds and of their diffusion through the gels.

Combined ultrasound and tissue plasminogen activator (rt-PA) therapy, or ultrasound enhanced thrombolysis (UET), has been shown to improve recanalization in patients with acute ischemic stroke. We measured the effect of ultrasound duty cycle on the lytic efficacy of 120 kHz UET in an in vitro human clot model. The hypothesis was that an increase in duty cycle increases rt-PA lytic efficacy. Human whole blood clots were exposed to 120-kHz ultrasound and rt-PA for 30 min in human plasma. The duty cycle ranged from 0% to 80%, where 0% represents sham exposure. Clot lytic rate was measured by recording the clot width over time. The clot width after 30 min exposure to rt-PA and ultrasound decreases with increasing duty cycle. The initial lytic rate increased linearly with duty cycle.

Unlabelled: Results of previous studies suggest that pacing strength stimuli can capture activation during ventricular arrhythmia locally near pacing sites. The existence of spatio-temporal distribution of excitable gap during arrhythmia suggests that multiple and timed stimuli delivered over a region may permit capture over larger areas., Objective of the Study: Our objective in this study was to evaluate the efficacy of using spatially distributed pacing (DP) to capture activation during ventricular arrhythmia., Methods: Data were obtained from rabbit hearts which were placed against a lattice of parallel wires through which biphasic pacing stimuli were delivered. Electrical activity was recorded optically. Pacing stimuli were delivered in sequence through the parallel wires starting with the wire closest to the apex and ending with one closest to the base. Inter-stimulus delay was based on conduction velocity. Time-frequency analysis of optical signals was used to determine variability in activation. A decrease in standard deviation of dominant frequencies of activation from a grid of locations that spanned the captured area and a concurrence with paced frequency were used as an index of capture., Results: Results from five animals showed that the average standard deviation decreased from 0.81 Hz during arrhythmia to 0.66 Hz during DP at pacing cycle length of 125 ms (p = 0.03) reflecting decreased spatio-temporal variability in activation during DP. Results of time-frequency analysis during these pacing trials showed agreement between activation and paced frequencies., Conclusions: These results show that spatially distributed and timed stimulation can be used to modify and capture activation during ventricular arrhythmia.

The aim of the present study was to validate the joint sensory impact of target compounds on the typicality degree of wine. Target compounds were selected from previous gas chromatography-olfactometry analysis. The preliminary experiment consisted in selecting odorants thought to have a positive effect on typical Chardonnay wines. Two sets of target compounds were chosen with regard to expected relationships between their concentrations and typicality scores. Target compounds were quantified in 20 wines. The second experiment was dedicated to the sensory evaluation of aroma models obtained by supplementation in wines. Three Chardonnay wines with intermediate typicality scores were supplemented with 6- or 10-compound combinations. The typicality degree of 24 samples was assessed by expert orthonasal perception. Wines supplemented with the 6-compound combinations were judged to be intermediate, whereas wines including the 10-compound combinations were considered to be quite representative of the Chardonnay concept. Such results confirm the active contribution of the 10 combined target compounds to typical Chardonnay wines.

Anorexic and bulimic patients have a highly distorted relationship with food and eating, even though they tend to be knowledgeable about diet and nutrition. The progress of this disease, as well as its complications and associated difficulties, are increasingly understood, while the etiopathogeny of eating disorders remains obscure. The approach that we are proposing involves the study of one of the most fundamental cognitive functions of human reasoning--the cognitive process of categorization. The purpose of this study is to understand the procedures used by these patients to construct representations of food. Categorization, one of the basic features of human cognition, allows individuals to organize their subjective experience of the surrounding environment by structuring its contents. This ability to group different objects into the same category based on their common characteristics is important for explaining the major cognitive activities of planning, memorization, communication and perception. Indeed, our categories reflect our conceptions of the world. They depend on our experiences and representations, as well as the expertise acquired in a specific field. The differences that appear in the categories created by subjects when they are asked to classify objects reveal the properties that are most salient to them and, as a result, the interests, values and ideas associated with these properties. There are three types of properties: perceptive properties, which describe the object's shape, color, odor and texture; structural properties, which relate to the object's components; and functional properties, which specify the way in which the object is used and provide an answer to the question, "What is it used for?". Subjects attribute these functional properties by means of knowledge or inference according to their representation of the object's role; such properties are especially likely to emerge during top-down (theory-driven) processing. The type of processing used (bottom-up or top-down) is dependent on a certain number of factors. We hypothesize, within the context of food product categorization, that patients suffering from eating disorders largely resort to processing based on acquired information or beliefs about the objects, i.e. top-down processing. We present two studies: a naturalistic and exploratory pilot study whose goal is to identify whether the various categorization processes used by eating disorder patients differ from those employed by subjects not suffering from an eating disorder. A second study aims to identify the different categorization procedures. During the first experiment, 68 women (17 control subjects, 17 anorexics, 17 anorexic bulimics and 17 bulimics) aged 18-39 (average age: 26.6) verbalize all representations that come to mind during a limited time period as the name of a food item is read. Eighty-nine food items are presented in alphabetical order. The list is read out loud and all comments are recorded. The data is processed in three ways : an analysis based on the positive or negative valence of each representation, an analysis based on each categories of food and an analysis of representations based on themes expressed. The three analyses (valence, categories of food and theme assigned to the representations) show differences between the representations of the four experimental groups. In fact, the anorexics and anorexic bulimics mainly express strongly negative representations about food, whereas bulimics and control produce representations whose positive and negative valences balances. These negative cognitions concern mainly meat for the control subjects and cakes for the subjects reached of TCA. Concerning theme assigned to the representations, the control subjects produce mainly cognitions relating to the hedonism, the flavor of food and their purpose on health. The anorexics and anorexics-bulimics evoke mainly the fat and sugar content of the foods. The bulimics evoke mainly cognitions relating to the effect on health and the intestinal transit time of food. These results lead one to believe that it is not the bulimic binging and purging of these patients, but rather their restrictive behavior that is the determining factor in the differences in food representations observed between the two experimental groups. During the second experiment, 60 women (15 controls, 15 anorexics, 15 anorexic bulimics and 15 bulimics) aged 18-32 (average age: 25.6) classified 27 food names according to their similarities and differences, and then explained the reasons for their categorizations. The data were analyzed in terms of similarity/difference, and the verbalizations were analyzed by content. The results indicate that 10 of the 27 foods were categorized differently by the controls and the subjects with eating disorders. Subjects classified the following foods: camembert cheese, cold cuts, cheese spread, fruit in syrup, whole milk, mayonnaise, bread, fresh fish, potatoes and plain yogurt. Bulimics and controls use similar classifications for food names, while anorexics and atypical bulimics classify foods in a similar way. Examining the categorization criteria used during verbalizations allows us to better understand these differences. The control group's major criterion seems to be the succession of dishes. These subjects group into separate categories entry foods (beef, eggs, fish, etc.), vegetables, cheese or dairy foods, and finally desserts. Additional foods, like bread and mayonnaise, belong to the same category. Other categories are nutritional criteria (for example, dairy products contain calcium) and biological criteria (for example, bananas and apples are fruits). These categorization criteria include structural properties (which describe what the object is made of) and functional, "academic" properties, those which describe how foods are used, "as in cookbooks or diet books." On the other hand, the categorization criteria expressed by anorexic patients are very different from those used by control subjects: foods that are hard to eliminate, rich, high-fat and therefore indigestible are considered to be similar. Some examples are cold cuts, potatoes, mayonnaise and prepared desserts. A second categorization criterion involves the concept of natural foods : certain foods "are unhealthy because they're processed, so they're bad for you"--one such example is cheese spread. A third criterion concerns the notion of familiar foods: poultry and eggs, for example, are "familiar to us." We are clearly seeing here the importance of functional properties in the categorization of food names: certain foods are indigestible, hard to eliminate, cause heartburn or reflux, are not natural, and thus are avoided. The categorization criteria mentioned by bulimic patients also clearly take into account the functional properties of foods. The criteria are of the following type: "it's filling, it relieves a bulimic attack, it helps prevent heartburn and constipation, etc." It appears that bulimics' categorization criteria are solely associated with these foods' imagined or real effect on the body. The categorization criteria used by anorexic bulimics seem to be especially associated with weight gain or the consumption of such foods during bulimia attacks because "they make you feel full." On the other hand, light foods, which patients allow themselves to eat, are placed in the same category. This study, which seeks to understand the cognitive functioning of eating disorder patients with anorexia and bulimia, has brought new elements to light. All patients exhibit food categorization processes that differ greatly from those displayed by control subjects. Patients also attribute greater significance to the functional properties of foods as compared to controls, who give priority to structural properties. Anorexic and bulimic patients base their food categorizations on the consequences of ingestion, in terms of health, digestion and weight gain. Their processing of food stimuli is therefore radically different and gives a dominating place to top-down processes. Additional studies should supplement these findings in order to gain a better understanding of patients' disturbed processing of information.

The release of isoamyl acetate from starch-based matrices was studied on the basis of a cumulative dynamic headspace analysis. Two corn starches were compared, which are known to yield pastes and gels differing in their structures and properties. These properties were assessed by viscometry and viscoelastic measurements. Aroma release was discussed as a function of the structure and texture parameters of the matrix. The release curves obtained from water and from the various starch-based matrices at 25 degrees C showed similar patterns but differed in their initial slopes and in the final plateau values. The lowest initial slopes were obtained for the normal starch dispersions that formed gels due to amylose gelation. The aroma compound was entirely released from water and from the waxy starch pastes. A significant amount of isoamyl acetate remained trapped in the normal starch dispersions.

Six French Chardonnay wines were submitted to both sensory and combined headspace/gas chromatography-olfactometry analyses. The detection frequencies allowed five hierarchical levels to be distinguished: P25, the odorant areas (OAs) having a detection frequency > or =25% (the complete olfactogram without the odor noise); P40, > or =40%; P55, > or =55%; P70, > or =70%; and P85, > or =85%. Moreover, the detection frequencies were analyzed to distinguish 21 discriminative OAs. Wines tested by sensory analysis and the headspace samples analyzed by gas chromatography-olfactometry (GC-O) were described by a heterogeneous vocabulary distributed into nine overall classes of descriptors. The new statistical treatment to examine hierarchical or discriminative OA categories with respect to sensory data used Generalized Procrustes analysis (GPA) from coordinate tables provided by correspondence analysis (CA). The successive data sets supplied by CA were subjected to GPA to yield consensus method maps. The more selective levels of detection frequency (P70 and P85) were responsible for incomplete or distorted information with respect to sensory data. The most appropriate segmentation of the OA distribution (olfactogram) to represent the sensory profile of the six samples would correspond to the intermediate pattern (P40 and P55). The other interest was to study the reasons of distortion due to the dynamic headspace extraction. The highest proportions of the variance were at all times related to the same classes: spicy, herbaceous, and, to a lesser degree, microbiological. This would indicate that the dynamic headspace analysis induces a distortion with respect to sensory data, which systematically affected the perception of both spicy and herbaceous characters of wines.

Introduction: A heart in fibrillation can be entrained by long-lasting alternating current (AC) stimuli, leading to defibrillation. To investigate the role entrainment plays in defibrillation, computer simulations of AC cardioversion in a three-dimensional slice of the canine heart were performed., Methods and Results: A bidomain finite element model of a 1-mm thick slice across the ventricles of a canine heart was used to simulate termination of transmural reentry with AC shocks. Cardioversion defibrillation thresholds (DFTs) were determined for 200-msec (L) AC shocks at varying frequencies. At the DFT, the entire tissue is entrained by the AC shock. DFT decreases as the frequency of the long-lasting AC shock increases. We hypothesize that this decrease is due to the short period of the high-frequency AC waveform, leaving strong virtual electrode polarization (VEP) after the shock ends. To test this hypothesis, the end-shock VEP were compared for different frequencies, demonstrating stronger polarization as frequency increased. To examine whether entrainment by the long-lasting AC shock contributes to the VEP at the end of the shock, additional simulations were conducted using single-period (Z) AC waveforms. Z waveform DFTs were higher than L waveform DFTs; the Z waveform VEP was weaker than the L waveform VEP at the same frequency. This indicates that entrainment contributes to the development of stronger VEP and, thus, to lower DFT at high frequencies., Conclusion: This study offers for the first time a mechanistic insight into cardioversion with long-lasting AC shocks.

Introduction: Cardiac tissue can be entrained when subjected to sinusoidal stimuli, often responding with action potentials sustained for the duration of the stimulus. To investigate mechanisms responsible for both entrainment and extended action potential duration, computer simulations of a two-dimensional grid of cardiac cells subjected to sinusoidal extracellular stimulation were performed., Methods and Results: The tissue is represented as a bidomain with unequal anisotropy ratios. Cardiac membrane dynamics are governed by a modified Beeler-Reuter model. The stimulus, delivered by a bipolar electrode, has a duration of 750 to 1,000 msec, an amplitude range of 800 to 3,200 microA/cm, and a frequency range of 10 to 60 Hz. The applied stimuli create virtual electrode polarization (VEP) throughout the sheet. The simulations demonstrate that periodic extracellular stimulation results in entrainment of the tissue. This phase-locking of the membrane potential to the stimulus is dependent on the location in the sheet and the magnitude of the stimulus. Near the electrodes, the oscillations are 1:1 or 1:2 phase-locked; at the middle of the sheet, the oscillations are 1:2 or 1:4 phase-locked and occur on the extended plateau of an action potential. The 1:2 behavior near the electrodes is due to periodic change in the voltage gradient between VEP of opposite polarity; at the middle of the sheet, it is due to spread of electrotonic current following the collision of a propagating wave with refractory tissue., Conclusion: The simulations suggest that formation of VEP in cardiac tissue subjected to periodic extracellular stimulation is of paramount importance to tissue entrainment and formation of an extended oscillatory action potential plateau.

Introduction: Cardiac tissue subjected to sinusoidal stimulus is characterized by action potentials (APs) that have extended plateau phases, sustained for the duration of the stimulus. Extended action potential durations (APDs) are beneficial because they disrupt wandering wavelets in the fibrillating heart. To investigate the mechanisms by which periodic stimulus affects cardiac tissue, particularly the development of sustained depolarization, computer simulations of single cardiac cells exposed to alternating current (AC) are performed., Methods and Results: Two modes of stimulation of the cell are examined: external field stimulation and transmembrane current injection. Several membrane models, including Luo-Rudy I and II, are used in the simulations. External AC field stimuli increase the APD of the single cell. The extended plateau of the cellular AP is characterized by periodic oscillations that are 1:2 phase locked with the applied stimulus. This specific behavior is due to the variations in stimulus magnitude and polarity along the cell border, which elicit opposite electrical responses from the cell sides. These pointwise responses are averaged in the macroscopic cellular response and result in sustained oscillatory depolarization that lasts for the duration of the stimulus. In contrast, the cell undergoing current injection does not develop an extended APD., Conclusion: The simulations demonstrate that variation of membrane potential within a cell is of paramount importance to the formation of an extended AP plateau in response to AC stimulation.

Thymic cysts are rare and almost always asymptomatic. The authors report the case of a 45 year old woman with a thymic cyst diagnosed after recurrent right sided heart failure resulting in signs suggestive of adiastole, regressing after "pleural" (mainly cystic) aspiration and diuretic therapy without any morphological or functional changes on Doppler echocardiography. This report concerns a rare tumour, with an exceptional volume (2 litres) extending down the cardiac borders and causing cardiac compression. It illustrates the diagnostic difficulty of a pathology with an unusual clinical presentation, despite complementary investigations including CT scan and MRI, very sensitive in this type of problem. A complete cure was obtained by total surgical ablation.

An atypical evolution of the mandibular cartilage was recorded in systematic dissections of the neck in the Anatomy Laboratory. This anomaly led to the formation of a supernumerary bony fragment in the concavity of the lower edge of the mandibular arch, with a slight adhesion thereto. This observation is reported by the authors after a recapitulation of the embryology.

Fragments of foetal pancreatic buds taken before the 10th week of gestation, stored at - 196 degrees C and cultivated on artificial media were implanted in an adult, insulin-dependent diabetic patient. Following a 2 weeks latent period, the clinical symptoms of diabetes regressed within 2 months, although all insulin treatment had been withdrawn. These results have now been maintained for 11 months, but major overloads in carbohydrates are imperfectly controlled.

The buccal ganglion of Aplysia contains three morpho-functional groups (A, B, and C) of large cells and two groups (s1 and s2) of small cells. The A cells evoke monoxynaptic IPSPs in the B cells. We found that s1 cells can evoke large EPSPs in the A cells, IEPSPs in the B cells, and EIIPSPs in the C cells; several s1 cells are able to evoke all three types of responses. Many s2 cells can evoke these same responses, but only in the A and B cells. Furthermore, the s cells can evoke depolarizing PSPs in other s cells; this relation is often reciprocal. All these responses may also be contralateral. Their monosynaptic nature is shown by the consistent 1:1 relationship with the presynaptic spike, and also by the effects of intracellular tetraethylammonium and of high Mg2+ concentration in the bathing medium. d-tubocurarine reversibly suppresses the I phase of the IEPSP evoked by the s cells in the B cells. All the responses evoked by the s cells undergo depression with repetition. The network formed by all these relations is outlined, and a double relationship proposed between s cells and B cells. By electrophysiological tracing of axonal pathways it is shown that the A cells send axons into the 3rd buccal nerve, the B cells into the 2nd and/or 3rd buccal nerve and in two cases into the radular nerve, and the C cells into the gastro-oesophageal nerve. Spontaneous synaptic activity of the buccal neurons appears to be formed mostly by the described PSPs. Spontaneous firing inside the isolated ganglion corresponds well to the alternate pattern of muscular contractions of the buccal mass.

Water, sodium and proteins renal excretion in with collodion Page's method hypertensive rats is compared with that of same Wistar strained control rats. Blood pressure of treated animals (n = 16) is 193.1 Hg mm (138 in control rats). Urinary flow increases from 19.5 to 33.7 ml/24 h (+ 72.8%), sodium excretion from 29.6 to 37.5 mg/24 h (+ 26.7%) and total proteins excretion from 23.5 to 63 mg/24 h (+ 169%. This data are correlated with the renal cortex morphological changes with photon and electron microscope. Severe damages are seen in Bowman's capsule and in glomerular copruscules, especially at the epithelial layer level. Important proteic pools occur within tubular lumen. Proximal tubular epithelium seems normal. On the other hand, distal tubular epithelium seriously scales. So, important water, sodium and proteins excretion increase in our experimental hypertension model can be explained. It is also discussed about functional and structural modifications analogy in our model's rats and in spontaneously hypertensive rats (SHB).

The depolarizing effect of various local anaesthetics (LA) on the membrane potential of Helix central neurons has been examined. There is a relation between depolarizing effect and concentration of LA in the bath that is linear over a range of concentrations. The slope of the curve is significantly higher for amethocaine (tetracaine) than for procaine while for dibucaine the dose-response relation is not linear. The blockade of a response to acetylcholine (ACh) is about two fold higher for dibucaine and amethocaine than for procaine. These results suggest that both amethocaine and procaine act at the ACh-site in addition to their binding with specific sites located within the ionic channel lumen; dibucaine appears to act through another mechanism.

Blood pressure and heart rate were recorded in spontaneously hypertensive rats (SH) and in their genetically normotensive precursors (WKY) during the sleep-wake cycle using a computer-assisted method. Similar results were obtained in both strains: (a) No significant difference was observed in blood pressure values between slow-wave-sleep (SWS) and the last 2 min of the preceding wakefulness (W) episode within the complete cycle; blood pressure then increased during PS. (b) Heart rate values during SWS were significantly lower than those computed for W; a further fall of heart rate was observed during paradoxical sleep (PS) only in hypertensive rats. (c) During SWS the blood pressure and heart rate variability was significantly lower than during W and PS. In addition, blood pressure variability values during the three sleep-wake states were lower in hypertensive than in normotensive rats. These data suggest that there are no qualitative differences in the mechanisms that control circulation during sleep in normotensive and spontaneous hypertensive rats.

26 programs of paraclinical tests for inpatients were written in diary form. Conditions of use were clearly defined with emphasis on optimal utilization of the first two or three days of the stay. Nine diaries are presented as examples. In order to reconcile various clinical, logical and economic requirements, the algorithm should oscillate between the flow-chart and the diary. For clinical evaluation, the flow-chart, completed by a health questionnaire, is satisfactory. But, for prescription of the first paraclinical tests, the diary appears more efficient under the specified conditions of use. The next step should then be a flow-chart, and so on. Flow-charts and diaries may be provided separately, each clinician having the possibility of alternating from one to the other, according to findings and local conditions.

1 Repetitive application of acetylcholine (ACh) revealed two types of ACh depolarization in two types of snail neurone, depending on their desensitization properties. 2 Further experiments were carried out on neurones which displayed a rapidly desensitizing response. 3 The amplitude of the response depended on the external sodium and calcium levels. 4 Procaine antagonized ACh effects with the same efficiency as atropine or hexamethonium, half maximal depression being obtained at a concentration of 10(-4) M. The blocking effect was independent of the dose of ACh. 5 The depression of the ACh-induced depolarization by cobalt ions and D600 suggests that calcium may participate in this response.

Blood pressure (BP) and heart rate (HR) were recorded in seven Sprague-Dawley rats during a total of 491 normal sleep-wake cycles with the use of a computer-assisted method developed for this study. Significant changes of BP, HR, and BP variability (BPV) were found between the three states within the cycle, i.e., wakefulness (W), slow-wave sleep (SWS), and paradoxical sleep (PS). The highest BP, BPV, and HR values were found during W. Then all cardiovascular (CV) variables fell during SWS, whereas BP and BPV rose again during PS. The fall of BPV observed during SWS was the most important CV change observed within the cycle. These state-dependent CV changes suggest that, in the rat, circulation during the sleep-wake cycle is controlled by the same central factors that operate in cats. In addition, significant BP and HR modifications between different cycles have been found. On the other hand, BP and HR differences between animals were also observed. The latter differences were found to be stable across the states, but no significant relation was found between BP and HR within any state. Thus the present data also suggest that BP and HR measurements are influenced not only by state-dependent factors but also by at least three different factors that are each independent of the state: one leads to BP and HR values that are influenced by the cycle the animal is in and the other two influence, respectively, the ranking of the individual's BP and HR levels within the population.