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Sample records for mitraclip system acute

  1. Progressive Mitral Stenosis After MitraClip Implantation in a Patient With Systemic Inflammatory Disease.

    PubMed

    Saji, Mike; Ailawadi, Gorav; Fowler, Dale E; LaPar, Damien J; Dent, John M; Ragosta, Michael; Lim, D Scott

    2016-08-01

    We describe a patient at high surgical risk who was successfully treated with a MitraClip (Abbott Vascular, Menlo Park, CA) without transmitral gradient. She received corticosteroid therapy for systemic lupus erythematosus, and progressive mitral stenosis developed late after MitraClip implantation. It gradually increased and reached 23 mm Hg at 28 months after the procedure; during the same period, her dose of prednisone had to be increased owing to lupus flare. Systemic inflammatory disease has the potential to result in mitral valve inflammation and fibrosis, ultimately causing thickening of the tissue bridge and worsening of the mitral valve obstruction. Preprocedural counseling regarding durability may help in this population. PMID:27449466

  2. Critical evaluation of the MitraClip system in the management of mitral regurgitation

    PubMed Central

    Deuschl, Florian; Schofer, Niklas; Lubos, Edith; Blankenberg, Stefan; Schäfer, Ulrich

    2016-01-01

    The MitraClip (MC) system is a device for percutaneous, transseptal edge-to-edge reconstruction of the mitral valve (MV) in patients with severe mitral regurgitation (MR) not eligible for surgery. Recently, a number of studies have underlined the therapeutic benefit of the MC system for patients with extreme and high risk for MV surgery suffering from either degenerative or functional MR. The MC procedure shows negligible intraprocedural mortality, low periprocedural complication rates, and a significant reduction in MR, as well as an improvement in functional capacity and most importantly quality of life. Presently, the MC system has become an additional interventional tool in the concert of surgical methods. It hereby enlarges the spectrum of MV repair for the Heart Team. Lately, many reviews focused on the MC system. The current review describes the developments in the treatment of MR with the MC system. PMID:26811687

  3. Simultaneous transfemoral transcatheter mitral and tricuspid valve edge-to-edge repair (using MitraClip system) completed by atrial septal defect occlusion in a surgically inoperable patient. First-in-human report

    PubMed Central

    Franz, Norbert; Ritter, Frank; Hofmann, Steffen; Stabel-Mahassine, Chourok; Warnecke, Henning; Thale, Joachim

    2015-01-01

    Transcatheter transfemoral mitral valve repair using the MitraClip system (Abbott Vascular, USA) is used in high-risk or inoperable patients with severe mitral regurgitation. We report the first-in-human simultaneous transfemoral clipping of the mitral and tricuspid valve completed by occlusion of an atrial septal defect (ASD). The procedure was performed in an 84-year-old patient in October 2015. After effective reduction of mitral and tricuspid regurgitations using the MitraClip system a PFO Occluder (St. Jude Medical, USA) was implanted. Transfemoral simultaneous mitral and tricuspid valve repair using the MitraClip system with ASD occlusion seems to be an effective therapy for high-risk or inoperable patients. PMID:26855642

  4. Simultaneous transfemoral transcatheter mitral and tricuspid valve edge-to-edge repair (using MitraClip system) completed by atrial septal defect occlusion in a surgically inoperable patient. First-in-human report.

    PubMed

    Kowalski, Marek; Franz, Norbert; Ritter, Frank; Hofmann, Steffen; Stabel-Mahassine, Chourok; Warnecke, Henning; Thale, Joachim

    2015-12-01

    Transcatheter transfemoral mitral valve repair using the MitraClip system (Abbott Vascular, USA) is used in high-risk or inoperable patients with severe mitral regurgitation. We report the first-in-human simultaneous transfemoral clipping of the mitral and tricuspid valve completed by occlusion of an atrial septal defect (ASD). The procedure was performed in an 84-year-old patient in October 2015. After effective reduction of mitral and tricuspid regurgitations using the MitraClip system a PFO Occluder (St. Jude Medical, USA) was implanted. Transfemoral simultaneous mitral and tricuspid valve repair using the MitraClip system with ASD occlusion seems to be an effective therapy for high-risk or inoperable patients. PMID:26855642

  5. Transcatheter treatment of chronic mitral regurgitation with the MitraClip system: an Italian consensus statement.

    PubMed

    Maisano, Francesco; Alamanni, Francesco; Alfieri, Ottavio; Bartorelli, Antonio; Bedogni, Francesco; Bovenzi, Francesco M; Bruschi, Giuseppe; Colombo, Antonio; Cremonesi, Alberto; Denti, Paolo; Ettori, Federica; Klugmann, Silvio; La Canna, Giovanni; Martinelli, Luigi; Menicanti, Lorenzo; Metra, Marco; Oliva, Fabrizio; Padeletti, Luigi; Parolari, Alessandro; Santini, Francesco; Senni, Michele; Tamburino, Corrado; Ussia, Gian P; Romeo, Francesco

    2014-03-01

    New percutaneous technologies are rapidly emerging for the treatment of structural heart disease including mitral valve disease. Preliminary data suggest a potential clinical benefit of percutaneous treatment of mitral regurgitation by the MitraClip procedure in selected patients. Until final data are available from randomized, controlled, multicenter clinical trials, there is an urgent need for a consensus among all the operators involved in the treatment of patients with mitral regurgitation, including clinical cardiologists, heart failure specialists, surgeons, interventional cardiologists, and imaging experts. In the absence of evidence-based guidelines, the heart-team approach is the most reliable method of making proper decisions. This study is the result of multidisciplinary consensus activity, and has the aim of helping physicians in the difficult task of making decisions for the treatment of patients with mitral regurgitation. It is the result of a joint effort of the major Italian Cardiology and Cardiac Surgery Societies, working together to find a proper balance between the points of view of the clinical cardiologist, the interventional cardiologist, and the cardiac surgeon. PMID:24662461

  6. Managing mitral regurgitation: focus on the MitraClip device

    PubMed Central

    Magruder, J Trent; Crawford, Todd C; Grimm, Joshua C; Fredi, Joseph L; Shah, Ashish S

    2016-01-01

    Based on the principle of surgical edge-to-edge mitral valve repair (MVR), the MitraClip percutaneous MVR technique has emerged as a minimally invasive option for MVR. This catheter-based system has been widely demonstrated to be safe, although inferior to surgical MVR. Studies examining patients with ≥3+ mitral regurgitation (MR) show that, for all patients treated, freedom from death, surgery, or MR ≥3+ is in the 75%–80% range 1 year following MitraClip implantation. Despite its inferiority to surgical therapy, in high-risk surgical patients, data suggest that the MitraClip system can be employed safely and that it can result in symptomatic improvement in the majority of patients, while not precluding future surgical options. MitraClip therapy also appears to reduce heart failure readmissions in the high-risk cohort, which may lead to an economic benefit. Ongoing study is needed to clarify the impact of percutaneous mitral valve clipping on long-term survival in high-risk populations, as well as its role in other patient populations, such as those with functional MR. PMID:27110142

  7. Two-year outcomes after percutaneous mitral valve repair with the MitraClip system: durability of the procedure and predictors of outcome

    PubMed Central

    Toggweiler, Stefan; Zuber, Michel; Sürder, Daniel; Biaggi, Patric; Gstrein, Christine; Moccetti, Tiziano; Pasotti, Elena; Gaemperli, Oliver; Faletra, Francesco; Petrova-Slater, Iveta; Grünenfelder, Jürg; Jamshidi, Peiman; Corti, Roberto; Pedrazzini, Giovanni; Lüscher, Thomas F; Erne, Paul

    2014-01-01

    Objective Analyse 2-year outcomes after MitraClip therapy and identify predictors of outcome. Methods Consecutive patients (n=74) undergoing MitraClip therapy were included in the MitraSWISS registry and followed prospectively. Results A reduction of mitral regurgitation (MR) to ≤ mild was achieved in 32 (43%) patients and to moderate in 31 (42%) patients; 16/63 (25%) patients with initially successful treatment developed recurrent moderate to severe or severe MR during the first year and only 1 patient did so during the second year. At 2 years, moderate or less MR was more frequently present in patients with a transmitral mean gradient <3 mm Hg at baseline (73% vs 23%, p < 0.01) and in patients with a left atrial volume index (LAVI) <50 mL/m2 at baseline (86% vs 52%, p=0.03). More than mild MR post MitraClip, N-terminal probrain natriuretic peptide ≥5000 ng/L at baseline, chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) were associated with reduced survival. Conclusions A mean transmitral gradient <3 mm Hg at baseline, an LAVI <50 mL/m2, the absence of COPD and CKD, and reduction of MR to less than moderate were associated with favourable outcome. Given a suitable anatomy, such patients may be excellent candidates for MitraClip therapy. Between 1 and 2 years follow-up, clinical and echocardiographic outcomes were stable, suggesting favourable, long-term durability of the device. PMID:25332799

  8. Comparison of three contemporary surgical scores for predicting all-cause mortality of patients undergoing percutaneous mitral valve repair with the MitraClip system (from the multicenter GRASP-IT registry).

    PubMed

    Adamo, Marianna; Capodanno, Davide; Cannata, Stefano; Giannini, Cristina; Laudisa, Maria Luisa; Barbanti, Marco; Curello, Salvatore; Immè, Sebastiano; Maffeo, Diego; Grasso, Carmelo; Bedogni, Francesco; Petronio, Anna Sonia; Ettori, Federica; Tamburino, Corrado

    2015-01-01

    The aim of this study was to explore the adaptability of 3 contemporary surgical scores (Logistic EuroSCORE [LES], EuroSCORE II [ESII], and Society of Thoracic Surgeons Predicted Risk of Mortality [STS-PROM]) for prediction of mortality after percutaneous mitral valve repair with the MitraClip system. A total of 304 patients from the multicenter Getting Reduction of mitrAl inSufficiency by Percutaneous clip implantation in ITaly registry (GRASP-IT) were stratified based on LES, ESII, and STS-PROM tertiles and analyzed by different measurements of discrimination, calibration, and global accuracy with focus on 30-day and 1-, 2-, and 3-year mortality. A statistically significant gradient in the distribution of mortality was observed at all time points with ESII, at 2 years with LES, and at 2 and 3 years with STS-PROM. ESII had the best discrimination at 30 days (C-statistic 0.80), which remained acceptable at later follow-up, being significantly superior to that of LES at each time point (p = 0.003 at 30 days, p = 0.005 at 1 year, p = 0.011 at 2 years, and p = 0.029 at 3 years). Compared with STS-PROM, ESII showed better discrimination at 30 days (C-statistic 0.80 vs 0.62, p = 0.023). All scores overpredicted the risk of mortality at 30 days and were miscalibrated at 2 and 3 years. At 1 year, there was a good agreement between the observed and predicted probabilities for ESII and STS-PROM, whereas LES remained overpredictive. ESII showed the best global accuracy at 30 days and 1 year, whereas no notable differences were noted versus LES and STS-PROM at 2 and 3 years. In conclusion, lacking specific tools for risk stratification of patients undergoing MitraClip implantation, ESII holds favorable prognostic characteristics, which makes it a valid surrogate. PMID:25456878

  9. Transcatheter mitral valve repair with mitraclip for significant mitral regurgitation long after heart transplantion.

    PubMed

    Ferraro, Paolo; Biondi-Zoccai, Giuseppe; Giordano, Arturo

    2016-07-01

    The role of transcatheter mitral valve repair with MitraClip implantation is becoming increasingly important for high-risk surgical patients with significant mitral regurgitation. Eligibility criteria for MitraClip are however rather strict, and the risk-benefit balance of this device in off-label settings remains unclear. Patients with prior heart transplantation may represent particularly challenging candidates for MitraClip, given their peculiar atrial anatomy. We hereby present the case of a 72-year-old gentleman with prior heart transplantation and significant mitral regurgitation who, after heart team consensus, was referred to us for MitraClip implantation. After careful planning, we were able to successfully implant two clips, achieving a significant improvement in the severity of the mitral regurgitation. Similarly favorable findings were confirmed at 3-month clinical and transthoracic/transesophageal echocardiographic follow-up. This clinical vignette highlights the key procedural milestones for successfully implanting MitraClip in patients with significant mitral regurgitation and prior heart transplantation. © 2015 Wiley Periodicals, Inc. PMID:26333048

  10. MitraClip therapy in mitral regurgitation: a Markov model for the cost-effectiveness of a new therapeutic option.

    PubMed

    Guerin, Patrice; Bourguignon, Sandrine; Jamet, Nicolas; Marque, Sébastien

    2016-07-01

    Introduction Mitral regurgitation is a heart condition resulting from blood flowing from the left ventricle towards the left atrium, increasing the risk of heart failure and mortality. While surgery can greatly reduce these risks, some patients are not eligible, resulting in medication being their only therapeutic alternative. The MitraClip (Abbot Vascular) is a medical device that is percutaneously implanted and designed to eliminate leaking of the mitral valve. Methods The efficacy of the MitraClip strategy vs medical management was assessed using a 4-state Markov model based on the mitral regurgitation grade (mitral regurgitation grade 0, I/II, and III/IV, and death). At each 1-month cycle, patients were or were not hospitalized. The model analyzed a fictional population of 1000 patients over a 5-year period from a national Health Insurance perspective. The primary end-point was the number of deaths avoided. Data from the EVEREST II High Risk Study patients were used along with a literature review. Results At 5 years, among the 1000 patients, 276 deaths were found to be avoidable with the MitraClip strategy. The incremental cost-effectiveness ratio (ICER) was €93,363 per death avoided. The annual ICER was calculated to take into consideration excess costs resulting from the MitraClip over the first year (€29,984 vs €8557 for the reference strategy) and the reduction of costs in following years (€3122 for MitraClip vs €8557 for reference strategy). Thus, the mean ICER was calculated to be €20,720 per death avoided. Conclusion The MitraClip is a novel alternative therapy for mitral insufficiency in patients ineligible for surgery that may offer a medico-economic advantage. PMID:26909557

  11. Development of mitral stenosis after single MitraClip insertion for severe mitral regurgitation.

    PubMed

    Cockburn, James; Fragkou, Paraskevi; Hildick-Smith, David

    2014-02-01

    We report the first case of mitral stenosis following Mitra-Clip insertion in a patient with symptomatic NYHA IV heart failure, secondary to severe mitral regurgitation (MR). A 79-year-old female with a history of prior aortic valve replacement underwent percutaneous mitral valve (MV) repair. A single clip was advanced coaxially down onto the MV under TOE guidance, with the anterior and posterior leaflets clipped together between A2 and P2. TOE confirmed a significant reduction in MR (grade 4 to grade 1). Despite initial symptomatic relief, she represented 3 months later with similar symptoms. Repeat TOE confirmed a well positioned Mitra-Clip with mild residual MR. However, the possibility of significant mitral stenosis was raised due to the presence of significant turbulence through the bi-orifice valve, with a peak gradient of 25 mm Hg. In addition there was evidence of severe functional tricuspid valve (TV) regurgitation with elevated pulmonary artery pressures (PAP 90 mm Hg), confirmed on subsequent right heart catheterization. After repeated heart team discussions and a failure of optimal medical therapy, and despite a logistic EuroScore of 35.5, minimally invasive surgical replacement of the MV and simultaneous TV repair was undertaken via a right thoracotomy. Despite procedural success and initial good postoperative response, the patient died subsequently from a combination of hospital-acquired pneumonia and significant gastrointestinal bleeding (post operative day 35). Mitra-Clip is a promising novel approach to MV repair. The establishment of further clinical and echocardiographic based selection criteria will help identify the correct patients for this treatment. PMID:23703973

  12. Atrial Septal Defect Closure for Right-to-Left Shunting Following a MitraClip Repair.

    PubMed

    Al'Aref, Subhi J; Bergman, Geoffrey; Wong, S Chiu

    2016-09-01

    Percutaneous repair of the mitral valve has been widely adopted for the treatment of primary, symptomatic severe mitral regurgitation in patients at prohibitive risk for surgical intervention. We present a case of an elderly female patient with moderate-to-severe mitral regurgitation who underwent MitraClip procedure, with postprocedural course remarkable for the development of right-to-left shunting and hypoxia, for which the patient underwent a percutaneous repair of the atrial septal defect with immediate recovery of oxygen saturation. PMID:27591693

  13. Functional effect of new atrial septal defect after percutaneous mitral valve repair using the MitraClip device.

    PubMed

    Hoffmann, Rainer; Altiok, Ertunc; Reith, Sebastian; Brehmer, Kathrin; Almalla, Mohammad

    2014-04-01

    Percutaneous mitral valve repair using the MitraClip device has become a therapeutic alternative for high surgical risk patients with symptomatic mitral regurgitation. The procedure involves transseptal puncture and results in a new atrial septal defect (ASD) after withdrawal of the 22Fr guiding catheter. The functional effect of the new ASD is not defined. In 28 patients with symptomatic mitral regurgitation undergoing percutaneous mitral valve repair using the MitraClip device, 3-dimensional transesophageal echocardiography was used to measure by direct en face imaging the area of the new ASD. Analysis of the velocity-time integral (VTI) across the ASD after withdrawal of the guiding catheter allowed calculation of the shunt volume. Diastolic VTI of the mitral flow was determined before and after withdrawal of the guiding catheter to determine left ventricular inflow changes. Invasive left atrial pressure measurements were obtained during withdrawal of the guiding catheter. Regurgitant volume was reduced from 86±21 ml/beat before intervention to 43±22 ml/beat after intervention. The new ASD had an area of 0.19 cm2, 44% of the area of the 22Fr guiding catheter. Considering the VTI across the septal defect of 72±26 cm/s, the left-to-right atrial shunt volume was calculated to be 14±6 ml/beat. The diastolic forward flow across the mitral valve was reduced by 13±6 ml/beat immediately after withdrawal of the MitraClip guiding catheter. Mean left atrial pressure was reduced from 17±8 mm Hg with the guiding catheter still in the left atrium to 15±8 mm Hg after withdrawal of the guiding catheter. In conclusion, the creation of a new ASD as consequence of the large-diameter MitraClip guiding catheter results in volume and pressure relief of the left atrium. This contributes to the immediate hemodynamic changes implemented by the MitraClip procedure. PMID:24513477

  14. Quantitation of mitral regurgitation after percutaneous MitraClip repair: comparison of Doppler echocardiography and cardiac magnetic resonance imaging

    PubMed Central

    Strugnell, Wendy; Gaikwad, Niranjan; Ischenko, Matthew; Speranza, Vicki; Chan, Jonathan; Neill, Johanne; Platts, David; Scalia, Gregory M.; Burstow, Darryl J.; Walters, Darren L.

    2015-01-01

    Objective Percutaneous valve intervention for severe mitral regurgitation (MR) using the MitraClip is a novel technology. Quantitative assessment of residual MR by transthoracic echocardiography (TTE) is challenging, with multiple eccentric jets and artifact from the clips. Cardiovascular magnetic resonance (CMR) is the reference standard for left and right ventricular volumetric assessment. CMR phase-contrast flow imaging has superior reproducibility for quantitation of MR compared to echocardiography. The objective of this study was to establish the feasibility and reproducibility of CMR in quantitating residual MR after MitraClip insertion in a prospective study. Methods Twenty-five patients underwent successful MitraClip insertion. Nine were excluded due to non-magnetic resonance imaging (MRI) compatible implants or arrhythmia, leaving 16 who underwent a comprehensive CMR examination at 1.5 T (Siemens Aera) with multiplanar steady state free precession (SSFP) cine imaging (cine CMR), and phase-contrast flow acquisitions (flow CMR) at the mitral annulus atrial to the MitraClip, and the proximal aorta. Same-day echocardiography was performed with two-dimensional (2D) visualization and Doppler. CMR and echocardiographic data were independently and blindly analyzed by expert readers. Inter-rater comparison was made by concordance correlation coefficient (CCC) with 95% confidence intervals (CIs), and Bland-Altman (BA) methods. Results Mean age was 79 years, and mean LVEF was 44%±11% by CMR and 54%±16% by echocardiography. Inter-observer reproducibility of echocardiographic visual categorical grading by expert readers was poor, with a CCC of 0.475 (−0.7, 0.74). Echocardiographic Doppler regurgitant fraction reproducibility was modest (CCC 0.59, 0.15-0.84; BA mean difference −3.7%, −38% to 31%). CMR regurgitant fraction reproducibility was excellent (CCC 0.95, 0.86-0.98; BA mean difference −2.4%, −11.9 to 7.0), with a lower mean difference and narrower

  15. Pigtail catheter "propping" for MitraClip percutaneous transcatheter mitral valve repair.

    PubMed

    Sandhu, Kully; Butler, Robert; Large, Adrian

    2016-08-01

    In recent years percutaneous therapy has emerged as a feasible and effective option for the treatment of mitral regurgitation, particularly in cases where the risks of conventional cardiac surgery are prohibitively high. To date the most widely used percutaneous approach is beating heart, edge-to-edge repair with the MitraClip device (Abbott Vascular-Structural Heart, Menlo Park, CA). The technique requires simultaneous grasping and approximation of both mitral valve leaflets prior to securing and releasing the clip. However, this may be technically challenging or indeed impossible in patients with failure of coaptation, particularly when there is a large coaptation gap. We present an approach for overcoming this relatively common obstacle based on "propping" the anterior mitral valve leaflet toward its posterior counterpart with a diagnostic pigtail catheter to reduce the coaptation gap and to allow grasping of both leaflets without difficulty. © 2016 Wiley Periodicals, Inc. PMID:26959728

  16. Acute transverse myelopathy complicating systemic lupus erythematosus.

    PubMed Central

    Propper, D J; Bucknall, R C

    1989-01-01

    A sixteen year old girl with systemic lupus erythematosus developed acute transverse myelopathy. She was treated with high dose steroids, cyclophosphamide, and plasma exchange and regained partial neurological function. Previous descriptions of transverse myelopathy complicating systemic lupus erythematosus are reviewed, with particular reference to the efficacy of high dose steroid treatment. PMID:2662918

  17. 78 FR 11208 - Circulatory System Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-15

    ... HUMAN SERVICES Food and Drug Administration Circulatory System Devices Panel of the Medical Devices... (FDA). The meeting will be open to the public. Name of Committee: Circulatory System Devices Panel of... approval application for the MitraClip Delivery System sponsored by Abbott Vascular. The system consists...

  18. One-year outcomes and predictors of mortality after MitraClip therapy in contemporary clinical practice: results from the German transcatheter mitral valve interventions registry

    PubMed Central

    Puls, Miriam; Lubos, Edith; Boekstegers, Peter; von Bardeleben, Ralph Stephan; Ouarrak, Taoufik; Butter, Christian; Zuern, Christine S.; Bekeredjian, Raffi; Sievert, Horst; Nickenig, Georg; Eggebrecht, Holger; Senges, Jochen; Schillinger, Wolfgang

    2016-01-01

    Aims The transcatheter mitral valve interventions (TRAMI) registry was established in order to assess safety and efficacy of catheter-based mitral valve interventional techniques in Germany, and prospectively enrolled 828 MitraClip patients (median age 76 years, median log. EuroSCORE I 20.0%) between August 2010 and July 2013. We present the 1-year outcome in this MitraClip cohort—which is the largest published to date. Methods and results Seven forty-nine patients (90.5%) were available for 1-year follow-up and included in the following analyses. Mortality, major adverse cardiovascular event rates, and New York Heart Association (NYHA) classes were recorded. Predictors of 1-year mortality were identified by multivariate analysis using a Cox regression model with stepwise forward selection. The 1-year mortality was 20.3%. At 1 year, 63.3% of TRAMI patients pertained to NYHA functional classes I or II (compared with 11.0% at baseline), and self-rated health status (on EuroQuol visual analogue scale) also improved significantly by 10 points. Importantly, a significant proportion of patients regained the complete independence in self-care after MitraClip implantation (independence in 74.0 vs. 58.6% at baseline, P = 0.005). Predictors of 1-year mortality were NYHA class IV (hazard ratio, HR 1.62, P = 0.02), anaemia (HR 2.44, P = 0.02), previous aortic valve intervention (HR 2.12, P = 0.002), serum creatinine ≥1.5 mg/dL (HR 1.77, P = 0.002), peripheral artery disease (HR 2.12, P = 0.0003), left ventricular ejection fraction <30% (HR 1.58, P = 0.01), severe tricuspid regurgitation (HR 1.84, P = 0.003), and procedural failure (defined as operator-reported failure, conversion to surgery, failure of clip placement, or residual post-procedural severe mitral regurgitation) (HR 4.36, P < 0.0001). Conclusions Treatment of significant MR with MitraClip resulted in significant clinical improvements in a high proportion of TRAMI patients after 12 months. In the TRAMI cohort

  19. Exploring waiving opportunities for mammalian acute systemic toxicity tests.

    PubMed

    Graepel, Rabea; Asturiol, David; Prieto, Pilar; Worth, Andrew P

    2016-07-01

    A survey was carried out to explore opportunities for waiving mammalian acute systemic toxicity tests. We were interested in finding out whether data from a sub-acute toxicity test could be used to predict the outcome of an acute systemic toxicity test. The survey was directed at experts in the field of toxicity testing, and was carried out in the context of the upcoming 2018 final registration deadline for chemicals under the EU REACH Regulation. In addition to the survey, a retrospective data analysis of chemicals that had already been registered with the European Chemicals Agency, and for which both acute and sub-acute toxicity data were available, was carried out. This data analysis was focused on chemicals that were administered via the oral route. The answers to the questionnaire showed a willingness to adopt waiving opportunities. In addition, the responses showed that data from a sub-acute toxicity test or dose-range finding study might be useful for predicting chemicals that do not require classification for acute oral toxicity (LD50 > 2000mg/kg body weight). However, with the exception of substances that fall into the non-classified category, it is difficult to predict current acute oral toxicity categories. PMID:27494626

  20. Systemic thrombolysis for acute pulmonary embolism.

    PubMed

    Bartel, Billie

    2015-01-01

    Acute pulmonary embolism is a frequent cause of hospitalization and is associated with a wide range of symptom severity. Anticoagulants are the mainstay of treatment for acute pulmonary embolism; however, in patients with massive or submassive pulmonary embolism, advanced therapy with thrombolytics may be considered. The decision to use thrombolytic therapy for acute pulmonary embolism should be based on careful risk-benefit analysis for each patient, including risk of morbidity and mortality associated with the embolism and risk of bleeding associated with the thrombolytic. Alteplase is currently the thrombolytic agent most studied and with the most clinical experience for this indication, although the most appropriate dose remains controversial, especially in patients with low body weight. When considering thrombolysis, unfractionated heparin is the preferred initial anticoagulant due to its short duration of action and its reversibility should bleeding occur. PMID:25559613

  1. VISUAL SYSTEM DYSFUNCTION FOLLOWING ACUTE TRIMETHYLTIN EXPOSURE IN RATS

    EPA Science Inventory

    Trimethyltin (TMT) has been shown to produce damage in the limbic system and several other brain areas. To date, damage to sensory systems has not been reported. The present study investigated the integrity of the visual system following acute exposure to TMT. Rats were chronical...

  2. Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

    PubMed

    Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

    2014-08-01

    Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. PMID:24929227

  3. Large-system acute care transformation.

    PubMed

    Tatman, Judy; Zauner, Janiece

    2014-01-01

    All organizations are steeped in making delivery model changes to address the changing health care landscape specific to the expectations of health care reform. Too often, these changes focus solely on improving processes rather than developing creative and innovative work processes that decrease waste and increase quality. The Providence Health and Services system has embraced the challenge to transform health care services from a large-system perspective, beginning with 1 region. The authors share the beginning stages of this innovative work, the unique contributions to health care processes, and the early outcomes on 2 patient care units. PMID:24317032

  4. Acute systemic histoplasmosis associated with chorioretinitis in an immunocompetent adolescent

    PubMed Central

    Fowler, Brian; Shen, Christopher; Mastellone, Joseph; Chaum, Edward

    2011-01-01

    Summary Histoplasmosis is an endemic, systemic mycosis caused by the dimorphic fungus Histoplasma capsulatum. A minority of patients develop asymptomatic chorioretinitis known as presumed ocular histoplasmosis syndrome (POHS), which is typically associated with chorioretinal scarring and peripapillary atrophy and occasionally with choroidal neovascularization secondary to maculopathy. We report a case of acute severe bilateral chorioretinitis associated with disseminated H. capsulatum in an immunocompetent adolescent boy living in an endemic area. The chorioretinitis did not respond to systemic antifungal therapy, but both his systemic illness and ocular lesions resolved with the addition of systemic steroids. PMID:23362391

  5. Decision support systems for robotic surgery and acute care

    NASA Astrophysics Data System (ADS)

    Kazanzides, Peter

    2012-06-01

    Doctors must frequently make decisions during medical treatment, whether in an acute care facility, such as an Intensive Care Unit (ICU), or in an operating room. These decisions rely on a various information sources, such as the patient's medical history, preoperative images, and general medical knowledge. Decision support systems can assist by facilitating access to this information when and where it is needed. This paper presents some research eorts that address the integration of information with clinical practice. The example systems include a clinical decision support system (CDSS) for pediatric traumatic brain injury, an augmented reality head- mounted display for neurosurgery, and an augmented reality telerobotic system for minimally-invasive surgery. While these are dierent systems and applications, they share the common theme of providing information to support clinical decisions and actions, whether the actions are performed with the surgeon's own hands or with robotic assistance.

  6. Central nervous system effects in acute thallium poisoning.

    PubMed

    Tsai, Yu-Tai; Huang, Chin-Chang; Kuo, Hung-Chou; Wang, Hsuan-Min; Shen, Wu-Shiun; Shih, Tung-Sheng; Chu, Nai-Shin

    2006-03-01

    We report the central nervous system manifestations, neuropsychological studies and brain magnetic resonance image (MRI) findings of two patients with acute thallium intoxication. Neurologically the patients suffered from confusion, disorientation, and hallucination in the acute stage, followed by anxiety, depression, lack of attention, and memory impairment, in addition to peripheral neuropathy. Neuropsychological tests revealed an impairment of memory function, including reversed digital span, memory registration, memory recall, memory recognition, similarity, proverb reasoning, and verbal fluency. High concentrations of thallium were found in the urine, blood, and drinking water of these two patients. Brain MRI showed lesions in the corpus striatum in one patient. During the follow-up periods, the clinical manifestations and neuropsychological studies showed a slowly progressive improvement, and a follow-up brain MRI 1.5 months later demonstrated a resolution of the lesions. We conclude that thallium intoxication might induce encephalopathy, and brain MRI studies demonstrated the acute-stage brain lesions in a severe intoxicated patient. In addition, neuropsychological tests also confirmed memory deficits, although the brain lesions in the corpus striatum might resolve. PMID:16337004

  7. Effects of acute oligohydramnios on respiratory system of fetal sheep.

    PubMed

    Savich, R D; Guerra, F A; Lee, C C; Padbury, J F; Kitterman, J A

    1992-08-01

    Prolonged oligohydramnios, or a lack of amniotic fluid, is associated with pulmonary hypoplasia and subsequent perinatal morbidity, but it is unclear whether short-term or acute oligohydramnios has any effect on the fetal respiratory system. To investigate the acute effects of removal of amniotic fluid, we studied nine chronically catheterized fetal sheep at 122-127 days gestation. During a control period, we measured the volume of fluid in the fetal potential airways and air spaces (VL), production rate of that fluid, incidence and amplitude of fetal breathing movements, tracheal pressures, and fetal plasma concentrations of cortisol, epinephrine, and norepinephrine. We then drained the amniotic fluid for a short period of time [24-48 h, 30.0 +/- 4.0 (SE) h] and repeated the above measurements. The volume of fluid drained for the initial studies was 1,004 +/- 236 ml. Acute oligohydramnios decreased VL from 35.4 +/- 2.9 ml/kg during control to 22.0 +/- 1.6 after oligohydramnios (P less than 0.004). Acute oligohydramnios did not affect the fetal lung fluid production rate, fetal breathing movements, or any of the other measured variables. Seven repeat studies were performed in six of the fetuses after reaccumulation of the amniotic fluid at 130-138 days, and in four of these studies the lung volume also decreased, although the overall mean for the repeat studies was not significantly different (27.0 +/- 5.2 ml/kg for control vs. 25.5 +/- 5.5 ml/kg for oligohydramnios). Again, none of the other measured variables were altered by oligohydramnios in the repeat studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1399988

  8. Systemic blood coagulation activation in acute coronary syndromes

    PubMed Central

    Undas, Anetta; Szułdrzyński, Konstanty; Brummel-Ziedins, Kathleen E.; Tracz, Wiesława; Zmudka, Krzysztof

    2009-01-01

    We evaluated systemic alterations to the blood coagulation system that occur during a coronary thrombotic event. Peripheral blood coagulation in patients with acute coronary thrombosis was compared with that in people with stable coronary artery disease (CAD). Blood coagulation and platelet activation at the microvascular injury site were assessed using immunochemistry in 28 non-anticoagulated patients with acute myocardial infarction (AMI) versus 28 stable CAD patients matched for age, sex, risk factors, and medications. AMI was associated with increased maximum rates of thrombin-antithrombin complex generation (by 93.8%; P < .001), thrombin B-chain formation (by 57.1%; P < .001), prothrombin consumption (by 27.9%; P = .012), fibrinogen consumption (by 27.0%; P = .02), factor (f) Va light chain generation (by 44.2%; P = .003), and accelerated fVa inactivation (by 76.1%; P < .001), and with enhanced release of platelet-derived soluble CD40 ligand (by 44.4%; P < .001). FVa heavy chain availability was similar in both groups because of enhanced formation and activated protein C (APC)–mediated destruction. The velocity of coagulant reactions in AMI patients showed positive correlations with interleukin-6. Heparin treatment led to dampening of coagulant reactions with profiles similar to those for stable CAD. AMI-induced systemic activation of blood coagulation markedly modifies the pattern of coagulant reactions at the site of injury in peripheral vessels compared with that in stable CAD patients. PMID:18931343

  9. Use of four MitraClip devices in a patient with ischemic cardiomyopathy and mitral regurgitation: "zipping by clipping".

    PubMed

    Kische, Stephan; Nienaber, Christoph; Ince, Hüseyin

    2012-11-15

    Severe mitral regurgitation (MR) as a consequence of underlying left ventricular dysfunction substantially contributes to morbidity and mortality. A variety of percutaneous treatment options for mitral valve repair have been developed; however, most of these techniques are still at an early stage of clinical evaluation. Today, percutaneous edge-to-edge mitral valve repair using the MitraClip® system is the only endovascular approach that demonstrated noninferiority when compared with standard surgical repair in a randomized trial. However, a considerable number of patients with functional MR will present with extensive annulus dilatation and minimal vertical leaflet coaptation that potentially preclude them from this beneficial technology for anatomical reasons. In this report, we portray a 72-year-old man presenting with end-stage systolic heart failure and severe functional MR as a consequence of long-standing coronary artery disease. Recently, his clinical course was complicated by intractable hemodynamic instability and recurrent pulmonary edema. High predicted mortality and progressive physical decay rendered this moribund patient a candidate for salvage percutaneous mitral valve repair. During the endovascular procedure, a central systolic coaptation gap of 7 mm proved to be too wide for adequate simultaneous grasping of both leaflets. Consideration was given to an alternative approach by means of our novel "zipping technique." Through the trans-septal route, medial to lateral approximation of the tethered leaflets was successfully achieved by intentional deployment of four MitraClip® devices. With the first in-human application of four mechanical implants, a profound reduction of MR grade has been accomplished by the creation of a lateral neo-orifice with apparent acute clinical success. However, it needs to be determined whether successful application of the zipping technique leads to sustained reverse ventricular remodeling and will translate into an

  10. Systemic tuberculosis presenting with acute transient myopia: a case report

    PubMed Central

    Aslam, Sher A; Kashani, Shahram; Morley, Roland K

    2008-01-01

    Introduction Transient myopia has been reported to occur in a number of conditions, either ocular in origin or associated with an underlying systemic cause. We present a rare case of this abnormality occurring in the setting of systemic tuberculosis. Case presentation A 29-year-old Indian woman presented with sudden onset blurred distance vision and fever. Examination revealed visual acuity of counting fingers in both eyes improving to 6/9 with pinhole with N5 reading acuity. Anterior segment examination revealed narrow angles on gonioscopy. Posterior segments were normal. Systemic examination revealed a fluctuant mass in her left loin, aspiration of which yielded pus which was culture-positive for Mycobacterium tuberculosis. The Mantoux test elicited a strongly positive reaction. Chest X-ray and magnetic resonance imaging of the brain were unremarkable. Computed tomography scan and magnetic resonance imaging of the spine and abdomen revealed a large psoas abscess communicating with the loin mass. Two vertebrae were involved but not the spinal cord or canal. Conclusion Transient myopia is a rare presenting feature of systemic tuberculosis. A postulated mechanism in this patient is that development of a uveal effusion related to systemic tuberculosis caused anterior rotation of the iris-lens diaphragm, thereby inducing narrowing of the angle and acute myopia. PMID:19014689

  11. Epigenetic coordination of acute systemic inflammation: potential therapeutic targets

    PubMed Central

    Vachharajani, Vidula; Liu, Tiefu; McCall, Charles E.

    2015-01-01

    Epigenetic reprogramming of thousands of genes directs the course of acute systemic inflammation, which is highly lethal when dysregulated during sepsis. No molecular-based treatments for sepsis are available. A new concept supports that sepsis is an immunometabolic disease and that loss of control of nuclear epigenetic regulator Sirtuin 1 (SIRT-1), a NAD+ sensor directs immune and metabolic pathways during sepsis. SIRT-1, acting as homeostasis checkpoint, controls hyper and hypo inflammatory responses of sepsis at the microvascular interface, which disseminates inflammatory injury to cause multiple organ failure. Modifying SIRT-1 activity, which can prevent or treat established sepsis in mice, may provide a new way treat sepsis by epigenetically restoring immunometabolic homeostasis. PMID:25088223

  12. Markers of acute neuropsychiatric systemic lupus erythematosus: a multidisciplinary evaluation.

    PubMed

    Abda, Essam A; Selim, Zahraa I; Radwan, Moustafa E M; Mahmoud, Nagham M; Herdan, Omar M; Mohamad, Khalid A; Hamed, Sherifa A

    2013-05-01

    This study was aimed to assess: (1) the additive diagnostic utility of diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA) over conventional MRI in detecting brain lesions in patients with acute primary neuropsychiatric systemic lupus erythematosus (NPSLE), and (2) the relevance of their findings to the associated NP manifestations. Included were 34 patients with acute NPSLE with mean age of 33.26 ± 10.14 years and duration of illness of 3.33 ± 1.71 years. Clinical interviewing and psychiatric and cognitive evaluations were performed by applying the criteria of the diagnostic and statistical manual of mental health disorders criteria (DSM-IV), Stanford Binet Subset Testing, Mini-Mental State Examination and Wechsler Memory Scale-Revised. Serologic tests included looking for antinuclear antibodies, anti-double strand DNA, anti-phospholipid antibodies. Radiologic evaluation included conventional MRI, DWI and MRA. One or more NP manifestations were diagnosed in 28 patients, in which cognitive deficits were reported with headache, psychosis and CVS. Anti-phospholipid antibodies were reported in patients with CVS. Twenty patients (71.43 %) with primary NPSLE (n = 28) had MRI abnormalities in which hyperintense signals at subcortical and periventricular white matter and at the junction between the gray and white matter represented 75 % (n = 15) and with headache (n = 6), psychosis (n = 6) and acute confusional state (n = 3) with and without cognitive deficits, respectively. Moderate-sized infarctions with restricted diffusion in the distribution of middle cerebral arteries were represented in 35 % (n = 7) and with CVS, of them, 71.43 % (n = 5) had beading and focal narrowing of carotid arteries were consistent with vasculitis. Brain atrophy represented 20 % (n = 4) and with psychosis. Compared to those with normal MRI, patients with MRI abnormalities were older (P < 0.050) and had longer duration of illness (P < 0.050). To conclude, although DWI

  13. Making post-acute care assets viable: a system's approach to continuing care.

    PubMed

    Lemon, Jeffery S; Oberst, Larry; Griffin, Kathleen M

    2013-04-01

    To build a strong continuing care network, leaders at Spectrum Health: Recruited industry veterans in post-acute care, Increased the visibility of the parent brand, Gained greater alignment throughout the system, Filled gaps in the health system's post-acute care portfolio. PMID:23596835

  14. Sumatriptan iontophoretic transdermal system for the acute treatment of migraine.

    PubMed

    Vikelis, Michail; Mitsikostas, Dimos D; Rapoport, Alan M

    2014-03-01

    SUMMARY We will describe the pharmacokinetic profile, clinical efficacy and safety data of the sumatriptan iontophoretic transdermal system (Zecuity®, NuPathe Inc., PA, USA), recently approved for the acute treatment of migraine with or without aura in adults, by the US FDA. This transdermal system utilizes a low-level electrical current to deliver sumatriptan transdermally and circumvents the GI tract. Pharmacokinetic studies have shown that iontophoretic delivery of sumatriptan achieves detectable plasma concentrations 15 min after activation with a maximum mean serum concentration of 22 ng/ml. A randomized, double-blind, controlled clinical trial demonstrated minimal triptan-related side effects and superior efficacy versus placebo. The pain-free rate at 2 h postdose was 18% of patients applying the sumatriptan patch versus 9% using the placebo (p = 0.0092). This sumatriptan transdermal system may be a good choice for migraineurs with severe nausea or vomiting, those with intolerable triptan-related adverse events and/or those not responding optimally to oral medications. PMID:24641436

  15. The role of the immune system in central nervous system plasticity after acute injury

    PubMed Central

    Giusto, Elena; Mallucci, Giulia; Marchetti, Bianca; Pluchino, Stefano

    2014-01-01

    Acute brain injuries cause rapid cell death that activates bidirectional crosstalks between the injured brain and the immune system. In the acute phase, the damaged central nervous system (CNS) activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, which would ultimately bring the inflammatory reaction to a close. In the chronic phase, a sustained immune activation is described in many CNS disorders, and the degree of this prolonged response has variable effects on the spontaneous brain regenerative processes. The challenge for treating acute CNS damages is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Here we have reviewed the available information about the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of recovery after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that ultimately are associated to intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. PMID:24785677

  16. Acute acalculous cholecystitis in systemic lupus erythematosus: a rare initial manifestation.

    PubMed

    Manuel, Valdano; Pedro, Gertrudes Maria; Cordeiro, Lemuel Bornelli; de Miranda, Sandra Maria da Rocha Neto

    2016-01-01

    Acute acalculous cholecystitis is a very rare gastrointestinal manifestation in systemic lupus erythematosus and becomes rarer as an initial manifestation. There are only two cases reported. The authors report a 20-year-old black woman that presented acute acalculous cholecystitis revealed by abdominal computed tomography. During hospitalization, she was diagnosed systemic lupus erythematosus. Conservative treatment with antibiotics was performed with complete remission of the symptoms. Corticosteroid was started in ambulatory. Cholecystectomy has been the treatment of choice in acute acalculous cholecystitis as a complication of systemic lupus erythematosus. The patient responded well to conservative treatment, and surgery was not required. This case is unique in the way that corticosteroid was started in ambulatory care. We should not forget that the acute acalculous cholecystitis can be the initial presentation of systemic lupus erythematosus although its occurrence is very rare. Conservative treatment should be considered. Abdominal computed tomography was a determinant exam for better assessment of acute acalculous cholecystitis. PMID:27267533

  17. Risk of viral acute gastrointestinal illness from non-disinfected drinking water distribution systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute gastrointestinal illness (AGI) resulting from pathogens directly entering the piping of drinking water distribution systems is insufficiently understood. Here, we estimate AGI incidence attributable to virus intrusions into non-disinfecting municipal distribution systems. Viruses were enumerat...

  18. The role of the immune system in central nervous system plasticity after acute injury.

    PubMed

    Peruzzotti-Jametti, L; Donegá, M; Giusto, E; Mallucci, G; Marchetti, B; Pluchino, S

    2014-12-26

    Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. PMID:24785677

  19. Influence of acute renal failure on the mononuclear phagocytic system.

    PubMed

    Sousa, V R; Sousa, A A; Petroianu, A; Simal, C J; Barbosa, A J

    2001-09-01

    Several studies show the ability of macrophages to remove particles injected into the bloodstream. This function seems to be increased in the presence of acute renal failure. The objective of the present study was to assess the phagocytic function of the main organs (spleen, liver and lung) of the mononuclear phagocytic system in renal and postrenal failures. Fifteen rats (250-350 g) were divided into three groups (N = 5): group I - control; group II - ligature of both ureters, and group III - bilateral nephrectomy. On the third postoperative day, all animals received an iv injection of 1 ml/kg 99mTc sulfur colloid. Blood samples were collected for the assessment of plasma urea, creatinine, sodium, and potassium concentrations and arterial gasometry. Samples of liver, spleen, lung and blood clots were obtained and radioactivity was measured. Samples of liver, spleen, lung and kidney were prepared for routine histopathological analysis. Plasma urea, creatinine and potassium concentrations in groups II and III were higher than in group I (P<0.05). Plasma sodium concentrations in groups II and III were lower than in group I (P<0.05). Compensated metabolic acidosis was observed in the presence of postrenal failure. Group II animals showed a lower level of radioactivity in the spleen (0.98) and lung (2.63), and a higher level in the liver (105.51) than control. Group III animals showed a lower level of radioactivity in the spleen (11.94) and a higher level in the liver (61.80), lung (11.30) and blood clot (5.13) than control. In groups II and III liver steatosis and bronchopneumonia were observed. Renal and postrenal failures seem to interfere with blood clearance by the mononuclear phagocytic system. PMID:11514841

  20. An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

    PubMed

    Mascio, Heather M; Joya, Christie A; Plasse, Richard A; Baker, Thomas P; Flessner, Michael F; Nee, Robert

    2015-08-01

    Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration. PMID:25500295

  1. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-04-07

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  2. Mechanical thrombectomy for acute ischemic stroke in pregnancy using the penumbra system.

    PubMed

    Aaron, Sanjith; Shyamkumar, N K; Alexander, Sunithi; Babu, P Suresh; Prabhakar, A T; Moses, Vinu; Murthy, T V; Alexander, Mathew

    2016-01-01

    Even though intravenous thrombolysis with tissue plasminogen activator (IV tPA) is the standard of care in acute ischemic stroke, its use in pregnancy is not clearly defined. Mechanical thrombectomy devices can be an option; however, literature on the use of such mechanical devices in stroke in pregnancy is lacking. Here we describe two cases that developed acute embolic stroke during pregnancy who were successfully treated by mechanical clot retrieval using the Penumbra system 28 (Penumbra Inc., Alameda, California, USA). To the best of our knowledge, these are the only case reports on the use of the Penumbra device in pregnant patients with acute ischemic stroke. PMID:27293343

  3. Mechanical thrombectomy for acute ischemic stroke in pregnancy using the penumbra system

    PubMed Central

    Aaron, Sanjith; Shyamkumar, N. K.; Alexander, Sunithi; Babu, P. Suresh; Prabhakar, A. T.; Moses, Vinu; Murthy, T. V.; Alexander, Mathew

    2016-01-01

    Even though intravenous thrombolysis with tissue plasminogen activator (IV tPA) is the standard of care in acute ischemic stroke, its use in pregnancy is not clearly defined. Mechanical thrombectomy devices can be an option; however, literature on the use of such mechanical devices in stroke in pregnancy is lacking. Here we describe two cases that developed acute embolic stroke during pregnancy who were successfully treated by mechanical clot retrieval using the Penumbra system 28 (Penumbra Inc., Alameda, California, USA). To the best of our knowledge, these are the only case reports on the use of the Penumbra device in pregnant patients with acute ischemic stroke. PMID:27293343

  4. Promoting patient-centred fundamental care in acute healthcare systems.

    PubMed

    Feo, Rebecca; Kitson, Alison

    2016-05-01

    Meeting patients' fundamental care needs is essential for optimal safety and recovery and positive experiences within any healthcare setting. There is growing international evidence, however, that these fundamentals are often poorly executed in acute care settings, resulting in patient safety threats, poorer and costly care outcomes, and dehumanising experiences for patients and families. Whilst care standards and policy initiatives are attempting to address these issues, their impact has been limited. This discussion paper explores, through a series of propositions, why fundamental care can be overlooked in sophisticated, high technology acute care settings. We argue that the central problem lies in the invisibility and subsequent devaluing of fundamental care. Such care is perceived to involve simple tasks that require little skill to execute and have minimal impact on patient outcomes. The propositions explore the potential origins of this prevailing perception, focusing upon the impact of the biomedical model, the consequences of managerial approaches that drive healthcare cultures, and the devaluing of fundamental care by nurses themselves. These multiple sources of invisibility and devaluing surrounding fundamental care have rendered the concept underdeveloped and misunderstood both conceptually and theoretically. Likewise, there remains minimal role clarification around who should be responsible for and deliver such care, and a dearth of empirical evidence and evidence-based metrics. In explicating these propositions, we argue that key to transforming the delivery of acute healthcare is a substantial shift in the conceptualisation of fundamental care. The propositions present a cogent argument that counters the prevailing perception that fundamental care is basic and does not require systematic investigation. We conclude by calling for the explicit valuing and embedding of fundamental care in healthcare education, research, practice and policy. Without this

  5. Review article: liver support systems in acute hepatic failure.

    PubMed

    Rahman, T M; Hodgson, H J

    1999-10-01

    The treatment of acute hepatic failure has developed rapidly over the last 40 years, reducing morbidity and mortality from this syndrome. Whilst this has been partly attributed to significant improvements in the specialist medical management of these patients, advances in surgical techniques and pharmaceutical developments have led to the establishment of successful liver transplantation programmes, which have improved mortality significantly. This review will examine the clinical impact of alternative methods that have been used to provide extra-corporeal hepatic support. Non-biological, bio- logical and hybrid hepatic extra-corporeal support will be explored, offering a comprehensive historical overview and an appraisal of present and future advances. PMID:10540040

  6. Systemic Mastocytosis Presenting as Acute Appendicitis: A Case Report and Review of the Literature

    PubMed Central

    A. Akbar, Syed; Raza, Shahzad; E. Denney, Jason; J. Johannesen, Eric; C. Doll, Donald

    2013-01-01

    Systemic mastocytosis is characterized by abnormal growth and accumulation of mast cells in various organs. Gastrointestinal (GI) symptoms are common disease manifestations in this disease and can significantly impair the quality of life. Signs of GI systemic mastocytosis include steatorrhea, malabsorption, hepatomegaly, splenomegaly, portal hypertension, and ascites. Acute appendicitis as a presenting feature in systemic mastocytosis has not been reported in the literature previously. In this report, we discuss the case of a female patient with systemic mastocytosis (c-KIT D816V (+)) who was admitted for right-sided acute abdominal pain. Laboratory study revealed an normal white blood cell count with eosinophilia and an elevated serum tryptase level of 23 μg/l. CT of the abdomen and pelvis showed an enlarged appendix of 12 mm in diameter, with minimal wall enhancement. Laparoscopic appendectomy was performed. The appendix was found to be hyperemic and firm, and it was densely adherent to the posterior cecum, the surrounding peritoneal wall, and the overlying mesenteric fat. Pathology revealed acute appendicitis with greater than 30 mast cells per high-power field by immunoperoxidase studies with mast cell tryptase and CD117. The patient subsequently improved and was discharged home. This case is the first reported case with a histological diagnosis of acute appendicitis resulting from mast cell infiltration. Physicians should be aware of acute appendicitis as a manifestation of systemic mastocytosis. Prompt diagnosis and management may prevent potentially fatal complications of appendiceal perforation and peritonitis. PMID:23626557

  7. Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing

    PubMed Central

    Seidle, Troy; Robinson, Sally; Holmes, Tom; Creton, Stuart; Prieto, Pilar; Scheel, Julia; Chlebus, Magda

    2010-01-01

    Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or refining the use of animals, and (3) recommendations for future work in this area. PMID:20484382

  8. Neurogenic stunned myocardium - do we consider this diagnosis in patients with acute central nervous system injury and acute heart failure?

    PubMed

    Mierzewska-Schmidt, Magdalena; Gawecka, Agnieszka

    2015-01-01

    Neurogenic stunned myocardium (NSM) is defined as myocardial injury and dysfunction of a sudden onset, occurring after various types of acute brain injury as a result of an imbalance in the autonomic nervous system. The typical spectrum of clinically observed abnormalities includes acute left ventricular failure, not uncommonly progressing to cardiogenic shock with hypotension that requires inotropic agents, pulmonary oedema and various arrhythmias. Commonly-seen electrocardiographic changes include: prolonged QT interval, ST segment changes, T-wave inversion, a new Q-wave or U-wave. Echocardiography shows both an impaired both systolic and diastolic function of the left ventricle. Biochemical markers of NSM comprise metabolic acidosis and increased cardiac enzymes and markers: creatine kinase (CK), and CK-MB, troponin I and B-type natriuretic peptide. The main cause of NSM is myocardial injury induced by local catecholamine release from nerve endings within the myocardium. Recently, a theory has been proposed to classify NSM as one of the stress-related cardiomyopathies, together with Takotsubo cardiomyopathy, acute left ventricular failure in the critically ill, cardiomyopathy associated with pheochromacytoma and exogenous catecholamine administration. The occurrence of NSM increases the risk of life-threatening complications, death, and worsens neurologic outcome. As far as we know, treatment should generally focus on the underlying neurologic process in order to maximize neurologic recovery. Improvement in neurologic pathology leads to rapid improvement in cardiac function and its full recovery, as NSM is a fully reversible condition if the patient survives. Awareness of the existence of NSM and a deeper knowledge of its etiopathology may reduce diagnostic errors, optimise its treatment. PMID:25940334

  9. 78 FR 50495 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-19

    ... line FQHC Federally qualified health center FR Federal Register FTE Full-time equivalent FUH Follow-up... 42 CFR Parts 412, 413, 414, et al. Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long Term Care; Hospital Prospective Payment System and Fiscal...

  10. 75 FR 50041 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-16

    ..., phone 1-800-743-3951. Electronic Access This Federal Register document is also available from the... CFR Parts 412, 413, 415, et al. Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long Term Care Hospital Prospective Payment System Changes and FY2011...

  11. 77 FR 53257 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-31

    ... Printing Office Web page at: http://www.gpo.gov/fdsys/browse/collection.action?collectionCode=FR . Free... 42 CFR Parts 412, 413, 424, et al. Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective Payment System and Fiscal...

  12. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    PubMed Central

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-01-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries. PMID:27351915

  13. Blocking Neurogenic Inflammation for the Treatment of Acute Disorders of the Central Nervous System

    PubMed Central

    Lewis, Kate Marie; Turner, Renée Jade

    2013-01-01

    Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis. PMID:23819099

  14. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    NASA Astrophysics Data System (ADS)

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-06-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

  15. Harnessing the immune system in acute myeloid leukaemia.

    PubMed

    Austin, Rebecca; Smyth, Mark J; Lane, Steven W

    2016-07-01

    Acute myeloid leukaemia (AML) is an aggressive blood cancer caused by the proliferation of immature myeloid cells. The genetic abnormalities underlying AML affect signal transduction pathways, transcription factors and epigenetic modifiers. In solid tumours, it is emerging that the genetic landscape of the tumour has a direct effect on the anti-tumour immune responses and response to immunotherapeutic treatment. However, there remains little information as to whether genetic abnormalities affect anti-leukemic immune responses. This review discusses current knowledge of AML antigens and immune responses to AML with a particular focus on the role of T cells and natural killer cells. Understanding immune responses to AML has implications for the development and use of immunotherapies to treat AML patients with distinct genetic abnormalities. PMID:27247119

  16. Vascular Access System for Continuous Arterial Infusion of a Protease Inhibitor in Acute Necrotizing Pancreatitis

    SciTech Connect

    Ganaha, Fumikiyo; Yamada, Tetsuhisa; Yorozu, Naoya; Ujita, Masuo; Irie, Takeo; Fukuda, Yasushi; Fukuda, Kunihiko; Tada, Shimpei

    1999-09-15

    We used a vascular access system (VAS) for continuous arterial infusion (CAI) of a protease inhibitor in two patients with acute necrotizing pancreatitis. The infusion catheter was placed into the dorsal pancreatic artery in the first patient and into the gastroduodenal artery in the second, via a femoral artery approach. An implantable port was then connected to the catheter and was secured in a subcutaneous pocket prepared in the right lower abdomen. No complications related to the VAS were encountered. This system provided safe and uncontaminated vascular access for successful CAI for acute pancreatitis.

  17. Systemic corticosteroids in acute chest syndrome: friend or foe?

    PubMed

    Ogunlesi, Folasade; Heeney, Matthew M; Koumbourlis, Anastassios C

    2014-03-01

    Acute chest syndrome(ACS) is the most common pulmonary complication of sickle cell disease (SCD), the second most common cause of hospitalization and the primary cause of death in patients with sickle cell disease. Its highest prevalence is in early childhood. The pathogenesis of ACS is unknown but many predisposing conditions and mechanisms have been implicated including infections, pulmonary fat embolism, asthma and ischemic reperfusion injury. These conditions are associated with inflammation and therefore, the use of corticosteroids has been advocated because of their anti-inflammatory properties. Although, significant benefits from their use have been shown, there is great reluctance in using them because of reports of serious adverse effects, such as readmission to the hospital due rebound pain crisis, stroke, renal infarction, coma and even death. The current article reviews the evidence in favor and against the use of corticosteroids in ACS. Emphasis is given on the potential benefits vs. risks among the different types of corticosteroids, the importance of the dosing regimen and the role of underlying co-morbidities. PMID:24268617

  18. Acute Bilateral Tuberculous Pneumonia in a Patient with Systemic Lupus Erythematosus

    PubMed Central

    Bhat, Rama; Bhat, Nitin; D’Souza, Savio; Chenchaiah, Venkata

    2016-01-01

    Pulmonary tuberculosis is a common infection associated with immunocompromised state. It usually presents with fibrosis or fibrocavitary lesions in the lung. We report a case of bilateral tuberculous pneumonia of acute presentation in a young lady who was being treated for systemic lupus erythematosus. PMID:27437280

  19. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats

    EPA Science Inventory

    Acute ozone exposure increases circulating stress hormones and induces peripheral metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for ozone-induced systemic metabolic effects and lung injury. Male Wis...

  20. “Missing clot” during mechanical thrombectomy in acute stroke using Solitaire stent retrieval system

    PubMed Central

    Huded, Vikram; Nambiar, Vivek; De Souza, Romnesh; Bohra, Vikram; Ramankutty, Ritesh

    2016-01-01

    Stent retrieval system is an established treatment modality in acute ischemic stroke with large vessel occlusion. Here, we describe a complication which occurred during mechanical thrombectomy in three cases where the clot dislodged during retrieval. There was a possibility of the clot getting reinjected into the artery with possible dire consequences. PMID:27293350

  1. Evaluation of Clinical Alvarado Scoring System and CT Criteria in the Diagnosis of Acute Appendicitis

    PubMed Central

    Gunes Tatar, Idil; Yilmaz, Kerim Bora; Sahin, Alpaslan; Aydin, Hasan; Akinci, Melih; Hekimoglu, Baki

    2016-01-01

    Aim. The aim was to evaluate the clinical Alvarado scoring system and computed tomography (CT) criteria for the diagnosis of acute appendicitis. Material and Methods. 117 patients with acute abdominal pain who underwent abdominal CT were enrolled in this retrospective study. Patient demographics, clinical Alvarado scoring, CT images, and pathologic results of the patients were evaluated. Results. 39 of the 53 patients who were operated on had pathologically proven acute appendicitis. CT criteria of appendiceal diameter, presence of periappendiceal inflammation, fluid, appendicolith, and white blood cell (WBC) count were significantly correlated with the inflammation of the appendix. The best cut-off value for appendiceal diameter was 6.5 mm. The correlation between appendiceal diameter and WBC count was 80% (P = 0.01 < 0.05). The correlation between appendiceal diameter and Alvarado score was 78.7% (P = 0.01 < 0.05). Conclusion. Presence of CT criteria of appendiceal diameter above 6.5 mm, periappendiceal inflammation, fluid, and appendicolith should prompt the diagnosis of acute appendicitis. Since patients with acute appendicitis may not always show the typical signs and symptoms, CT is a helpful imaging modality for patients with relatively low Alvarado score and leukocytosis and when physical examination is confusing. PMID:27242926

  2. Nicotine-induced acute hyperactivity is mediated by dopaminergic system in a sexually dimorphic manner.

    PubMed

    Zhang, Yunpeng; Guo, Jing; Guo, Aike; Li, Yan

    2016-09-22

    Short-term exposure to nicotine induces positive effects in mice, monkeys and humans, including mild euphoria, hyperactivity, and enhanced cognition. However, the underlying neural basis and molecular mechanisms for these effects remain poorly understood. Here, using a video recording system, we find that acute nicotine administration induces locomotor hyperactivity in Drosophila, similar to observations made in higher model organisms. Suppressing dopaminergic neurons or down-regulating dopamine 1-like receptor (DopR) abolishes this acute nicotine response, but surprisingly, does so only in male flies. Using a GFP reconstitution across synaptic partners (GRASP) approach, we show that dopaminergic neurons possess potential synaptic connections with acetylcholinergic neurons in wide regions of the brain. Furthermore, dopaminergic neurons are widely activated upon nicotine perfusion in both sexes, while the response curve differs significantly between the sexes. Moreover, knockdown of the β1 nicotine acetylcholine receptor (nAChR) in dopaminergic neurons abolishes the acute nicotine response only in male flies, while panneural knock-down occurs in both sexes. Taken together, our results reveal that in fruit flies, dopaminergic neurons mediate nicotine-induced acute locomotor hyperactivity in a sexually dimorphic manner, and Drosophila β1 nAChR subunit plays a crucial role in this nicotine response. These findings provide important insights into the molecular and neural basis of acute nicotine effects, and the underlying mechanisms may play conserved roles across species. PMID:27365175

  3. Systemic inflammation induces acute working memory deficits in the primed brain: relevance for delirium

    PubMed Central

    Murray, Carol; Sanderson, David J.; Barkus, Chris; Deacon, Robert M.J.; Rawlins, J. Nicholas P.; Bannerman, David M.; Cunningham, Colm

    2012-01-01

    Delirium is an acute, severe neuropsychiatric syndrome, characterized by cognitive deficits, that is highly prevalent in aging and dementia and is frequently precipitated by peripheral infections. Delirium is poorly understood and the lack of biologically relevant animal models has limited basic research. Here we hypothesized that synaptic loss and accompanying microglial priming during chronic neurodegeneration in the ME7 mouse model of prion disease predisposes these animals to acute dysfunction in the region of prior pathology upon systemic inflammatory activation. Lipopolysaccharide (LPS; 100 μg/kg) induced acute and transient working memory deficits in ME7 animals on a novel T-maze task, but did not do so in normal animals. LPS-treated ME7 animals showed heightened and prolonged transcription of inflammatory mediators in the central nervous system (CNS), compared with LPS-treated normal animals, despite having equivalent levels of circulating cytokines. The demonstration that prior synaptic loss and microglial priming are predisposing factors for acute cognitive impairments induced by systemic inflammation suggests an important animal model with which to study aspects of delirium during dementia. PMID:20471138

  4. Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

    NASA Astrophysics Data System (ADS)

    Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

    2013-05-01

    Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

  5. Acute and prolonged complement activation in the central nervous system during herpes simplex encephalitis.

    PubMed

    Eriksson, Charlotta E; Studahl, Marie; Bergström, Tomas

    2016-06-15

    Herpes simplex encephalitis (HSE) is characterized by a pronounced inflammatory activity in the central nervous system (CNS). Here, we investigated the acute and prolonged complement system activity in HSE patients, by using enzyme-linked immunosorbent assays (ELISAs) for numerous complement components (C). We found increased cerebrospinal fluid concentrations of C3a, C3b, C5 and C5a in HSE patients compared with healthy controls. C3a and C5a concentrations remained increased also compared with patient controls. Our results conclude that the complement system is activated in CNS during HSE in the acute phase, and interestingly also in later stages supporting previous reports of prolonged inflammation. PMID:27235358

  6. Effect of acute systemic hypoxia on human cutaneous microcirculation and endothelial, sympathetic and myogenic activity.

    PubMed

    Paparde, Artūrs; Plakane, Līga; Circenis, Kristaps; Aivars, Juris Imants

    2015-11-01

    The regulation of cutaneous vascular tone impacts vascular vasomotion and blood volume distribution as a challenge to hypoxia, but the regulatory mechanisms yet remain poorly understood. A skin has a very compliant circulation, an increase in skin blood flow results in large peripheral displacement of blood volume, which could be controlled by local and systemic regulatory factors. The aim of this study was to determine the acute systemic hypoxia influence on blood flow in skin, local regulatory mechanism fluctuations and changes of systemic hemodynamic parameters. Healthy subjects (n=11; 24.9±3.7years old) participated in this study and procedures were performed in siting position. After 20min of acclimatization 15min of basal resting period in normoxia (pO2=21%) was recorded, followed by 20min in acute systemic hypoxia (pO2=12%), and after 15min of recovery period in normoxia (pO2=21%). HRV was used to evaluate autonomic nervous system activity to heart from systemic hemodynamic parameters which continuously evaluated cardiac output, total peripheral resistance and mean arterial blood pressure. Regional blood flow was evaluated by venous occlusion plethysmography and skin blood flow by laser-Doppler flowmetry. To evaluate local factor influences to cutaneous circulation wavelet analysis was used; fluctuations in the frequency intervals of 0.0095-0.021, 0.021-0.052, and 0.052-0.145Hz correspondingly represent endothelial, sympathetic, and myogenic activities. Our results from HRV data suggest that acute systemic hypoxia causes statistically significant increase of sympathetic (LF/HF; N1=0.46±0.25 vs. H=0.67±0.36; P=0.027) and decrease of parasympathetic (RMSSD; 80.0±43.1 vs. H=69.9±40.4, ms; P=0.009) outflow to heart. Acute hypoxia causes statistically significant increase of heart rate (RR interval; N1=960.3±174.5 vs. H=864.7±134.6, ms; P=0.001) and cardiac output (CO; N1=5.4 (5.2; 7.9) vs. H=6.7±1.4, l/min; P=0.020). Regional blood flow and vascular

  7. The Innate Immune System in Acute and Chronic Wounds

    PubMed Central

    MacLeod, Amanda S.; Mansbridge, Jonathan N.

    2016-01-01

    Significance: This review article provides an overview of the critical roles of the innate immune system to wound healing. It explores aspects of dysregulation of individual innate immune elements known to compromise wound repair and promote nonhealing wounds. Understanding the key mechanisms whereby wound healing fails will provide seed concepts for the development of new therapeutic approaches. Recent Advances: Our understanding of the complex interactions of the innate immune system in wound healing has significantly improved, particularly in our understanding of the role of antimicrobials and peptides and the nature of the switch from inflammatory to reparative processes. This takes place against an emerging understanding of the relationship between human cells and commensal bacteria in the skin. Critical Issues: It is well established and accepted that early local inflammatory mediators in the wound bed function as an immunological vehicle to facilitate immune cell infiltration and microbial clearance upon injury to the skin barrier. Both impaired and excessive innate immune responses can promote nonhealing wounds. It appears that the switch from the inflammatory to the proliferative phase is tightly regulated and mediated, at least in part, by a change in macrophages. Defining the factors that initiate the switch in such macrophage phenotypes and functions is the subject of multiple investigations. Future Directions: The review highlights processes that may be useful targets for further investigation, particularly the switch from M1 to M2 macrophages that appears to be critical as dysregulation of this switch occurs during defective wound healing. PMID:26862464

  8. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  9. [Acute adverse effects in transfusion. Proposals for the hemosurveillance system].

    PubMed

    Baptista González, Héctor

    2013-01-01

    The management model based on risk prevention has become a major influence in shaping policies for transfusion safety. There are approximately sixty interactions between the health worker and the patient during the transfusion process,representing the number of times where you have the opportunity to make a mistake.We present an analysis of the weaknesses of the National Blood System, with particular attention to the haemovigilance donor and patient. The proposals include the implementation of the National Blood containing the need to establish from the National Blood Safety, significant changes in the regulatory framework and the internal regulations of the Ministry of Health, the CNTS and COFEPRIS. Is required to promote and coordinate the collection of accurate information from the committees of transfusion medicine, which will be accompanied by an initial diagnosis from the National Survey of Blood. Requires notice to other forms of funding to ensure the viability of the projects operating blood bank. Finally, as a strategic resource, the blood is of public, so access should not be restricted. PMID:23435081

  10. Systemic lupus erythematosus presenting as acute lupus pneumonitis in a young female

    PubMed Central

    Chattopadhyay, B; Chatterjee, A; Maiti, A; Debnath, NB

    2015-01-01

    Acute lupus pneumonitis is a rare initial presentation of systemic lupus erythematosus (SLE). We report a 19-year-old female presenting with fever and recurrent hemoptysis with radiological evidence of parenchymal lung involvement with mild pleural effusion. Subsequent development of malar and discoid rash with anti-nuclear antibodies (ANA) and anti-dsDNA positivity clinched the diagnosis. Her clinical signs and symptoms resolved with a course of intravenous pulse methyl-prednisolone along with radiological resolution. PMID:25766350

  11. Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

    PubMed

    Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

    2016-08-01

    Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome. PMID:27356057

  12. Topical versus Systemic Antibiotics in the Treatment of Acute Superficial Skin Infections

    PubMed Central

    Belcon, Michael C.

    1979-01-01

    Use of antibiotics in some superficial skin infections is examined. The choice of a route of administration is dependent on a number of factors, including the site and extent of skin lesions, frequency of recurrence, and clinical and immunological state of the host. However, the consensus of various studies on the subject seem to indicate a preference for the systemic route in acute infectious dermatoses. PMID:423278

  13. Double-button Fixation System for Management of Acute Acromioclavicular Joint Dislocation

    PubMed Central

    Torkaman, Ali; Bagherifard, Abolfazl; Mokhatri, Tahmineh; Haghighi, Mohammad Hossein Shabanpour; Monshizadeh, Siamak; Taraz, Hamid; Hasanvand, Amin

    2016-01-01

    Background: Surgical treatments for acromioclavicular (AC) joint dislocation present with some complications. The present study was designed to evaluate the double-button fixation system in the management of acute acromioclavicular joint dislocation. Methods: This cross sectional study, done between February 2011 to June 2014, consisted of 28 patients who underwent surgical management by the double-button fixation system for acute AC joint dislocation. Age, sex, injury mechanism, dominant hand, side with injury, length of follow up, time before surgery, shoulder and hand (DASH), constant and visual analogue scale (VAS) scores, and all complications of the cases during the follow up were recorded. Results: The mean age of patients was 33.23±6.7 years. Twenty four patients (85.71%) were male and four (14.28%) were female. The significant differences were observed between pre-operation VAS, constant shoulder scores and post-operation measurements. There were not any significant differences between right and left coracoclavicular, but two cases of heterotrophic ossifications were recorded. The mean follow-up time was 16.17±4.38 months. Conclusion: According to the results, the double-button fixation system for management of acute acromioclavicular joint dislocation has suitable results and minimal damage to the soft tissues surrounding the coracoclavicular ligaments. PMID:26894217

  14. Systemic Lupus Erythematosus, Radiotherapy, and the Risk of Acute and Chronic Toxicity: The Mayo Clinic Experience

    SciTech Connect

    Pinn, Melva E.; Gold, Douglas G. M.; Petersen, Ivy A.; Osborn, Thomas G.; Brown, Paul D.; Miller, Robert C.

    2008-06-01

    Purpose: To determine the acute and chronic toxic effects of radiotherapy in patients with systemic lupus erythematosus (SLE). Methods and Materials: Medical records of 21 consecutive patients with SLE, who had received 34 courses of external beam radiotherapy and one low-dose-rate prostate implant, were retrospectively reviewed. Patients with discoid lupus erythematosus were excluded. Results: Median survival was 2.3 years and median follow-up 5.6 years. Eight (42%) of 19 patients evaluable for acute toxicity during radiotherapy experienced acute toxicity of Grade 1 or greater, and 4 (21%) had acute toxicity of Grade 3 or greater. The 5- and 10-year incidence of chronic toxicity of Grade 1 or greater was 45% (95% confidence interval [CI], 22-72%) and 56% (95% CI, 28-81%), respectively. The 5- and 10-year incidence of chronic toxicity of Grade 3 or greater was 28% (95% CI, 18-60%) and 40% (95% CI, 16-72%), respectively. Univariate analysis showed that chronic toxicity of Grade 1 or greater correlated with SLE renal involvement (p < 0.006) and possibly with the presence of five or more American Rheumatism Association criteria (p < 0.053). Chronic toxicity of Grade 3 or greater correlated with an absence of photosensitivity (p < 0.02), absence of arthritis (p < 0.03), and presence of a malar rash (p < 0.04). Conclusions: The risk of acute and chronic toxicity in patients with SLE who received radiotherapy was moderate but was not prohibitive of the use of radiotherapy. Patients with more advanced SLE may be at increased risk for chronic toxicity.

  15. Posterior reversible encephalopathy syndrome: an acute manifestation of systemic lupus erythematous.

    PubMed

    Chan, Dexter Yak Seng; Ong, Yin Sheng

    2013-09-01

    Stroke mimickers are common, and they represent a diagnostic dilemma for clinicians. Many, like posterior reversible encephalopathy syndrome (PRES), are easily reversible. The manifestation of PRES is characterised by headaches, convulsions, altered mental functioning and blindness. In most cases, computed tomography of the brain will show hypodense lesions in the parieto-occpitial lobe, which only further confounds the physician. Although this syndrome is uncommon, prompt and accurate recognition allows early treatment, which has been shown to produce favourable outcomes. Herein, we report the case of a 54-year-old woman, who presented with PRES, as an acute manifestation of systemic lupus erythematous (SLE) and lupus nephritis. The patient was initially thought to be experiencing an ischaemic stroke, but the diagnosis was later changed. On management of her underlying condition, her symptoms resolved. PRES should be recognised as an acute emergency manifestation of SLE. It should not be mistaken for an ischaemic stroke as inappropriate treatment could have adverse outcomes. PMID:24068069

  16. Renin-angiotensin system and its role in hyperoxic acute lung injury.

    PubMed

    Zhang, P X; Han, C H; Zhou, F J; Li, L; Zhang, H M; Liu, W W

    2016-01-01

    Oxygen is essential to sustain life, but at a high partial pressure oxygen may cause toxicity to the human body. These injuries to the lung are known as hyperoxic acute lung injury [HALI]). To date, numerous studies have been conducted to investigate the pathogenesis of HALI, for which some hypotheses have been proposed. Accumulating evidence indicates that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of some lung diseases, including acute lung injury (ALI), chronic obstructive pulmonary disease (COPD) and HALI. In this review, we briefly introduce the classic RAS, local (tissue) RAS and intracellular RAS, and we summarize findings on the relationship between local/classic RAS and HALI. The importance--and ambiguity--of the results of these studies indicate a need for further investigations of the RAS and its role in the patho- genesis of HALI. PMID:27416692

  17. Systemic corticosteroid monotherapy for clinically diagnosed acute rhinosinusitis: a randomized controlled trial

    PubMed Central

    Venekamp, Roderick P.; Bonten, Marc J.M.; Rovers, Maroeska M.; Verheij, Theo J.M.; Sachs, Alfred P.E.

    2012-01-01

    Background: Patients with acute rhinosinusitis are frequently encountered in primary care. Although corticosteroids are being increasingly used for symptom control, evidence supporting their use is inconclusive. We conducted a randomized controlled trial to examine the effectiveness of systemic corticosteroid monotherapy for clinically diagnosed, uncomplicated acute rhinosinusitis. Methods: We conducted a block-randomized, double-blind, placebo-controlled clinical trial at 54 primary care practices (68 family physicians) in the Netherlands between Dec. 30, 2008, and Apr. 28, 2011. Adult patients with clinically diagnosed acute rhinosinusitis were randomly assigned to receive either prednisolone 30 mg/d or placebo for 7 days and asked to complete a symptom diary for 14 days. The primary outcome measure was the proportion of patients with resolution of facial pain or pressure on day 7. Results: Of the 185 patients included in the trial (93 in the treatment group, 92 in the placebo group), 2 withdrew from the study and 9 were excluded from the primary analysis because of incomplete symptom reporting. The remaining 174 patients (88 in the treatment group, 86 in the placebo group) were included in the intention-to-treat analysis. The proportions of patients with resolution of facial pain or pressure on day 7 were 62.5% (55/88) in the prednisolone group and 55.8% (48/86) in the placebo group (absolute risk difference 6.7%, 95% confidence interval −7.9% to 21.2%). The groups were similar with regard to the decrease over time in the proportion of patients with total symptoms (combined symptoms of runny nose, postnasal discharge, nasal congestion, cough and facial pain) and health-related quality of life. Adverse events were mild and did not differ significantly between the groups. Interpretation: Systemic corticosteroid monotherapy had no clinically relevant beneficial effects among patients with clinically diagnosed acute rhinosinusitis. Netherlands Trial Register

  18. Fatality due to acute systemic fluoride poisoning following a hydrofluoric acid skin burn.

    PubMed

    Tepperman, P B

    1980-10-01

    Reports indicate that death due to hydrofluoric acid exposure is usually the result of inhalation of vapor causing pulmonary edema and fluoride poisoning. Absorption via the skin route of fluoride ion sufficient to cause serious systemic problems and even death has rarely been reported. A fatality resulting from a severe facial burn, which produced acute systemic fluoride poisoning with profound hypocalcemia and hypomagnesemia, is presented. The importance of proper personal protective equipment as well as the immediate initiation of first aid and appropriate medical measures, including the monitoring and replacement of serum calcium and magnesium, are emphasized. PMID:7431138

  19. Influence of the acute alcoholism on the phagocytic function of the mononuclear phagocytic system

    PubMed Central

    Sabino, KR; Petroianu, A; Alberti, LR

    2011-01-01

    Rationale:Alcoholics are more likely to have infections, mainly in the respiratory system. Alcohol seems to inhibit the immune system. Despite the extensive literature related to alcoholism, data related to the immune system are still not conclusive. Objective: The purpose of this study was to verify the influence of acute alcohol intake on colloid distribution in the organs of the mononuclear phagocyte system. Methods and Results: Thirteen male Swiss mice were divided into two groups: Group 1 (n = 5) – control, and Group 2 (n = 8) – animals that received 0.5 ml ethanol 50%, 30 minutes before the experiment. Colloidal sulphur labeled with ⁸⁸mTc was used to evaluate colloid distribution in the liver, spleen and lungs. Colloid clearance was assessed as well. A gamma camera was used to measure the radioactivity of these organs and of a blood clot. No difference was found in the presence of colloid in the organs of both groups. The liver showed the highest phagocytic intake, followed by the spleen and lungs (p = 0.021 for Group 1 and p = 0.003 for Group 2). A minimum amount of radiation remained in the blood of both groups. Discussion: According to the experiential conditions of this work, acute ingestion of alcohol did not interfere with the phagocytic function of the mononuclear phagocyte system in mice. PMID:22514578

  20. The usage of the Boussignac continuous positive airway pressure system in acute respiratory failure.

    PubMed

    Wong, D T; Tam, A D; Van Zundert, T C R V

    2013-05-01

    Traditionally, continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP) devices have been used to treat patients in acute respiratory failure. However they require an electric power source, are relatively large in size, and may be difficult to use in prehospital settings. The recently introduced Boussignac CPAP system is capable of delivering 10 cmH2O of CPAP, is compact, portable and requires only an oxygen source. This paper reviews the efficacy of using Boussignac CPAP as a treatment for acute respiratory failure in both prehospital and hospital settings. All studies mainly focused on patients treated for cardiogenic pulmonary edema. In the prehospital setting, Boussigac CPAP significantly improved respiratory parameters and oxygenation from baseline values. In the emergency department setting, Boussignac CPAP was more effective than standard oxygen delivery and just as effective as BiPAP in improving patient oxygenation and respiration. In one study, implementing Boussignac CPAP reduced intubation rate and hospital stay. Most hospital staff found Boussignac CPAP easy to use and complication rates were low. Boussigac CPAP is a useful device in the treatment of patients with acute respiratory failure, especially in the prehospital setting. PMID:23419338

  1. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    SciTech Connect

    Yoo, Seong Ho; Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2013-07-05

    Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI.

  2. Alteration in systemic vascular resistance and cardiac output during acute cellular rejection and recovery in heart transplant recipients.

    PubMed

    Garan, Arthur R; Uriel, Nir; Sayer, Gabriel; Sims, Daniel; Zahner, Doris; Farr, Maryjane; Mancini, Donna; Jorde, Ulrich P

    2010-03-01

    Coronary vascular reserve is impaired during acute cellular rejection of the orthotopically transplanted heart, but changes in the peripheral vasculature during rejection have not been well described. To investigate whether peripheral vascular compensatory mechanisms are preserved after orthotopic heart transplantation (OHT), we longitudinally observed systemic vascular resistance (SVR) and cardiac output (CO) during acute cellular rejection. CO decreased during high-grade acute cellular rejection, and maintenance of mean arterial pressure was achieved by increases in SVR, and these changes did not return to baseline until several months after histologic resolution of rejection. PMID:19875310

  3. Capability of Using Clinical Care Classification System to Represent Nursing Practice in Acute Setting in Taiwan

    PubMed Central

    Feng, Rung-Chuang; Tseng, Kuan-Jui; Yan, Hsiu-Fang; Huang, Hsiu-Ya; Chang, Polun

    2012-01-01

    This study examines the capability of the Clinical Care Classification (CCC) system to represent nursing record data in a medical center in Taiwan. Nursing care records were analyzed using the process of knowledge discovery in data sets. The study data set included all the nursing care plan records from December 1998 to October 2008, totaling 2,060,214 care plan documentation entries. Results show that 75.42% of the documented diagnosis terms could be mapped using the CCC system. A total of 21 established nursing diagnoses were recommended to be added into the CCC system. Results show that one-third of the assessment and care tasks were provided by nursing professionals. This study shows that the CCC system is useful for identifying patterns in nursing practices and can be used to construct a nursing database in the acute setting. PMID:24199066

  4. Acute systemic exposure to silver-based nanoparticles induces hepatotoxicity and NLRP3-dependent inflammation.

    PubMed

    Ramadi, Khalil B; Mohamed, Yassir A; Al-Sbiei, Ashraf; Almarzooqi, Saeeda; Bashir, Ghada; Al Dhanhani, Aisha; Sarawathiamma, Dhanya; Qadri, Shahnaz; Yasin, Javed; Nemmar, Abderrahim; Fernandez-Cabezudo, Maria J; Haik, Yousef; Al-Ramadi, Basel K

    2016-10-01

    Nanoparticles (NPs) are increasingly being commercialized for use in biomedicine. NP toxicity following acute or chronic exposure has been described, but mechanistic insight into this process remains incomplete. Recent evidence from in vitro studies suggested a role for NLRP3 in NP cytotoxicity. In this study, we investigated the effect of systemic administration of composite inorganic NP, consisting of Ag:Cu:B (dose range 1-20 mg/kg), on the early acute (4-24 h post-exposure) and late phase response (96 h post-exposure) in normal and NLRP3-deficient mice. Our findings indicate that systemic exposure (≥2 mg/kg) was associated with acute liver injury due to preferential accumulation of NP in this organ and resulted in elevated AST, ALT and LDH levels. Moreover, within 24 h of NP administration, there was a dose-dependent increase in intraperitoneal neutrophil recruitment and upregulation in gene expression of several proinflammatory mediators, including TNF-α, IL-1β and S100A9. Histological analysis of liver tissue revealed evidence of dose-dependent hepatocyte necrosis, increase in sinusoidal Kupffer cells, lobular granulomas and foci of abscess formation which were most pronounced at 24 h following NP administration. NP deposition in the liver led to a significant upregulation in gene expression of S100A9, an endogenous danger signal recognition molecule of phagocytes, IL-1β and IL-6. The extent of proinflammatory cytokine activation and hepatotoxicity was significantly attenuated in mice deficient in the NLRP3 inflammasome, demonstrating the critical role of this innate immune system recognition receptor in the response to NP. PMID:26956548

  5. Reduction of the systemic inflammatory induced by acute cerebral infarction through ultra-early thrombolytic therapy

    PubMed Central

    YE, LICHAO; CAI, RUOWEI; YANG, MEILI; QIAN, JIAQIANG; HONG, ZHILIN

    2015-01-01

    Acute ischemic stroke induces systemic inflammation, exhibited as changes in body temperature, white blood cell counts and C-reactive protein (CRP) levels. The aim of the present study was to observe the effects of intravenous thrombolytic therapy on inflammatory indices in order to investigate the hypothesis that post-stroke systemic inflammatory response occurs in response to the necrosis of brain tissues. In this study, 62 patients with acute cerebral infarction and indications for intravenous thrombolysis were divided into three groups on the basis of their treatment and response: Successful thrombolysis (n=36), failed thrombolysis (n=12) and control (n=14) groups. The body temperature, white blood cell counts and high-sensitivity (hs)-CRP levels were recorded pre-treatment and on post-stroke days 1, 3, 5 and 7. Spearman's correlation analysis showed that the pre-treatment National Institutes of Health Stroke Scale (NIHSS) score positively correlated with body temperature, white blood cell count and hs-CRP levels. On day 3 of effective intravenous thrombolysis, the body temperature and white blood cell were decreased and on days 3 and 5, the serum levels of hs-CRP were reduced compared with those in the failed thrombolysis and control groups. The results indicate that the systemic inflammatory response following acute cerebral infarction was mainly caused by ischemic injury of local brain tissue; the more serious the stroke, the stronger the inflammatory response. Ultra-early thrombolytic therapy may inhibit the necrosis of brain tissue and thereby reduce the inflammatory response. PMID:26622513

  6. Acute respiratory distress syndrome due to systemic lupus erythematosus with hemophagocytic syndrome: an autopsy report.

    PubMed

    Kaneko, Kazuma; Matsuda, Masayuki; Sekijima, Yoshiki; Hosoda, Waki; Gono, Takahisa; Hoshi, Kenichi; Shimojo, Hisashi; Ikeda, Shu-ichi

    2005-04-01

    This report concerns a patient with systemic lupus erythematosus (SLE) who died of acute respiratory distress syndrome (ARDS) 1 day after the onset of pulmonary symptoms. Autopsy demonstrated severe hemophagocytosis in the bone marrow and histopathology indicating a marked increase in vascular permeability in both lungs and kidneys. In this patient, active SLE and associated hemophagocytic syndrome may have induced an increase in the production of inflammatory cytokines, which immediately induced ARDS. Since fatal ARDS can occur as a life-threatening complication of SLE, careful observation is necessary, particularly when there are clinical findings suggestive of associated hemophagocytic syndrome. PMID:15338452

  7. Clinical significance of automatic warning function of cardiac remote monitoring systems in preventing acute cardiac episodes

    PubMed Central

    Chen, Shou-Qiang; Xing, Shan-Shan; Gao, Hai-Qing

    2014-01-01

    Objective: In addition to ambulatory Holter electrocardiographic recording and transtelephonic electrocardiographic monitoring (TTM), a cardiac remote monitoring system can provide an automatic warning function through the general packet radio service (GPRS) network, enabling earlier diagnosis, treatment and improved outcome of cardiac diseases. The purpose of this study was to estimate its clinical significance in preventing acute cardiac episodes. Methods: Using 2 leads (V1 and V5 leads) and the automatic warning mode, 7160 patients were tested with a cardiac remote monitoring system from October 2004 to September 2007. If malignant arrhythmias or obvious ST-T changes appeared in the electrocardiogram records was automatically transferred to the monitoring center, the patient and his family members were informed, and the corresponding precautionary or therapeutic measures were implemented immediately. Results: In our study, 274 cases of malignant arrhythmia, including sinus standstill and ventricular tachycardia, and 43 cases of obvious ST-segment elevation were detected and treated. Because of early detection, there was no death or deformity. Conclusions: A cardiac remote monitoring system providing an automatic warning function can play an important role in preventing acute cardiac episodes. PMID:25674124

  8. A severe case of acute exogenous lipoid pneumonia treated with systemic corticosteroid.

    PubMed

    Yasui, Hideki; Yokomura, Koshi; Suda, Takafumi

    2016-01-01

    Acute exogenous lipoid pneumonia is a rare disorder in adults. A treatment of choice for lipoid pneumonia has not been established, and systemic corticosteroid use remains controversial. We report the case of a 32-year-old man with schizophrenia who presented with kerosene-induced acute exogenous lipoid pneumonia that was treated with a systemic corticosteroid. In this case, supportive therapy did not improve the patient's condition, so systemic corticosteroid therapy was commenced four days after he ingested the kerosene. After corticosteroid commencement, the patient's symptoms and hypoxia improved within a few days. Although some radiological characteristics of this disorder have been reported previously, the process of radiological improvement of exogenous lipoid pneumonia is not well known. In this case, computed tomography findings changed dramatically after corticosteroid therapy was initiated. Extensive bilateral consolidations that were observed on admission improved. Although pneumatoceles developed two weeks after corticosteroid commencement, they were nearly gone after two months of the treatment. While corticosteroid therapy is not suitable for all cases, it should be considered for severe or refractory cases. PMID:27222789

  9. A severe case of acute exogenous lipoid pneumonia treated with systemic corticosteroid

    PubMed Central

    Yasui, Hideki; Yokomura, Koshi; Suda, Takafumi

    2016-01-01

    Acute exogenous lipoid pneumonia is a rare disorder in adults. A treatment of choice for lipoid pneumonia has not been established, and systemic corticosteroid use remains controversial. We report the case of a 32-year-old man with schizophrenia who presented with kerosene-induced acute exogenous lipoid pneumonia that was treated with a systemic corticosteroid. In this case, supportive therapy did not improve the patient's condition, so systemic corticosteroid therapy was commenced four days after he ingested the kerosene. After corticosteroid commencement, the patient's symptoms and hypoxia improved within a few days. Although some radiological characteristics of this disorder have been reported previously, the process of radiological improvement of exogenous lipoid pneumonia is not well known. In this case, computed tomography findings changed dramatically after corticosteroid therapy was initiated. Extensive bilateral consolidations that were observed on admission improved. Although pneumatoceles developed two weeks after corticosteroid commencement, they were nearly gone after two months of the treatment. While corticosteroid therapy is not suitable for all cases, it should be considered for severe or refractory cases. PMID:27222789

  10. Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis.

    PubMed

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-04-01

    Upon hemolysis extracellular hemoglobin causes oxidative stress and cytotoxicity due to its peroxidase activity. Extracellular hemoglobin may release free hemin, which increases vascular permeability, leukocyte recruitment, and adhesion molecule expression. Pancreatitis-associated ascitic fluid is reddish and may contain extracellular hemoglobin. Our aim has been to determine the role of extracellular hemoglobin in the local and systemic inflammatory response during severe acute pancreatitis in rats. To this end we studied taurocholate-induced necrotizing pancreatitis in rats. First, extracellular hemoglobin in ascites and plasma was quantified and the hemolytic action of ascitic fluid was tested. Second, we assessed whether peritoneal lavage prevented the increase in extracellular hemoglobin in plasma during pancreatitis. Third, hemoglobin was purified from rat erythrocytes and administered intraperitoneally to assess the local and systemic effects of ascitic-associated extracellular hemoglobin during acute pancreatitis. Extracellular hemoglobin and hemin levels markedly increased in ascitic fluid and plasma during necrotizing pancreatitis. Peroxidase activity was very high in ascites. The peritoneal lavage abrogated the increase in extracellular hemoglobin in plasma. The administration of extracellular hemoglobin enhanced ascites; dramatically increased abdominal fat necrosis; upregulated tumor necrosis factor-α, interleukin-1β, and interleukin-6 gene expression; and decreased expression of interleukin-10 in abdominal adipose tissue during pancreatitis. Extracellular hemoglobin enhanced the gene expression and protein levels of vascular endothelial growth factor (VEGF) and other hypoxia-inducible factor-related genes in the lung. Extracellular hemoglobin also increased myeloperoxidase activity in the lung. In conclusion, extracellular hemoglobin contributes to the inflammatory response in severe acute pancreatitis through abdominal fat necrosis and inflammation

  11. Java interface to a computer-aided diagnosis system for acute pulmonary embolism using PIOPED findings

    NASA Astrophysics Data System (ADS)

    Frederick, Erik D.; Tourassi, Georgia D.; Gauger, Matthew; Floyd, Carey E., Jr.

    1999-05-01

    An interface to a Computer Aided Diagnosis (CAD) system for diagnosis of Acute Pulmonary Embolism (PE) from PIOPED radiographic findings was developed. The interface is based on Internet technology which is user-friendly and available on a broad range of computing platforms. It was designed to be used as a research tool and as a data collection tool, allowing researchers to observe the behavior of a CAD system and to collect radiographic findings on ventilation-perfusion lung scans and chest radiographs. The interface collects findings from physicians in the PIOPED reporting format, processes those findings and presents them as inputs to an artificial neural network (ANN) previously trained on findings from 1,064 patients from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study. The likelihood of PE predicted by the ANN and by the physician using the system is then saved for later analysis.

  12. Uncoupling of the autonomic and cardiovascular systems in acute brain injury.

    PubMed

    Goldstein, B; Toweill, D; Lai, S; Sonnenthal, K; Kimberly, B

    1998-10-01

    We hypothesized that acute brain injury results in decreased heart rate (HR) variability and baroreflex sensitivity indicative of uncoupling of the autonomic and cardiovascular systems and that the degree of uncoupling should be proportional to the degree of neurological injury. We used HR and blood pressure (BP) power spectral analysis to measure neuroautonomic regulation of HR and BP and the transfer function magnitude (TF) between BP and HR as a measure of baroreflex modulation of HR. In 24 brain-injured patients [anoxic/ischemic injury (n = 7), multiple trauma (n = 6), head trauma (n = 5), central nervous system infection (n = 4), and intracranial hemorrhage (n = 2)], neurological injury and survival was associated with low-frequency (0.01-0.15 Hz) HR and BP power and TF. Brain-dead patients showed decreased low-frequency HR power [0. 51 +/- 0.36 (SE) vs. 2.54 +/- 0.14 beats/min2, P = 0.03] and TF [0. 61 +/- 0.16 (SE) vs. 1.29 +/- 0.07 beats . min-1 . mmHg-1, P = 0.05] compared with non-brain-dead patients. We conclude that 1) severity of neurological injury and outcome are inversely associated with HR and BP variability and 2) there is direct evidence for cardiovascular and autonomic uncoupling in acute brain injury with complete uncoupling during brain death. PMID:9756562

  13. Pathophysiological roles of adrenomedullin-RAMP2 system in acute and chronic cerebral ischemia.

    PubMed

    Igarashi, Kyoko; Sakurai, Takayuki; Kamiyoshi, Akiko; Ichikawa-Shindo, Yuka; Kawate, Hisaka; Yamauchi, Akihiro; Toriyama, Yuichi; Tanaka, Megumu; Liu, Tian; Xian, Xian; Imai, Akira; Zhai, Liuyu; Owa, Shinji; Koyama, Teruhide; Uetake, Ryuichi; Ihara, Masafumi; Shindo, Takayuki

    2014-12-01

    The accessory protein RAMP2 is a component of the CLR/RAMP2 dimeric adrenomedullin (AM) receptor and is the primary determinant of the vascular functionality of AM. RAMP2 is highly expressed in the brain; however, its function there remains unclear. We therefore used heterozygous RAMP2 knockout (RAMP2+/-) mice, in which RAMP2 expression was reduced by half, to examine the actions of the endogenous AM-RAMP2 system in cerebral ischemia. To induce acute or chronic ischemia, mice were subjected to middle cerebral artery occlusion (MCAO) or bilateral common carotid artery stenosis (BCAS), respectively. In RAMP2+/- mice subjected to MCAO, recovery of cerebral blood flow (CBF) was slower than in WT mice. AM gene expression was upregulated after infarction in both genotypes, but the increase was greater in RAMP2+/- mice. Pathological analysis revealed severe nerve cell death and demyelination, and a higher level of oxidative stress in RAMP2+/- mice. In RAMP2+/- mice subjected to BCAS, recovery of cerebral perfusion was slower and less complete than in WT mice. In an 8-arm radial maze test, RAMP2+/- mice required more time to solve the maze and showed poorer reference memory. They also showed greater reductions in nerve cells and less compensatory capillary growth than WT mice. These results indicate the AM-RAMP2 system works to protect nerve cells from both acute and chronic cerebral ischemia by maintaining CBF, suppressing oxidative stress, and in the case of chronic ischemia, enhancing capillary growth. PMID:25252154

  14. Mechanism for the acute effects of organophosphate pesticides on the adult 5-HT system.

    PubMed

    Judge, Sarah J; Savy, Claire Y; Campbell, Matthew; Dodds, Rebecca; Gomes, Larissa Kruger; Laws, Grace; Watson, Anna; Blain, Peter G; Morris, Christopher M; Gartside, Sarah E

    2016-02-01

    The neurotransmitter serotonin (5-HT) is involved in mood disorder aetiology and it has been reported that (organophosphate) OP exposure affects 5-HT turnover. The aim of this study was to elucidate the mechanism underlying OP effects on the adult 5-HT system. First, acute in vivo administration of the OP diazinon (0, 1.3, 13 or 39 mg/kg i.p.) to male Hooded Lister rats inhibited the activity of the cholinergic enzyme acetylcholinesterase in blood and in the hippocampus, dorsal raphe nucleus (DRN), striatum and prefrontal cortex. Diazinon-induced cholinesterase inhibition was greatest in the DRN, the brain's major source of 5-HT neurones. Second, acute in vivo diazinon exposure (0 or 39 mg/kg i.p.) increased the basal firing rate of DRN neurones measured ex vivo in brain slices. The excitatory responses of DRN neurones to α1-adrenoceptor or AMPA/kainate receptor activation were not affected by in vivo diazinon exposure but the inhibitory response to 5-HT was attenuated, indicating 5-HT1A autoreceptor down-regulation. Finally, direct application of the diazinon metabolite diazinon oxon to naive rat brain slices increased the firing rate of DRN 5-HT neurones, as did chlorpyrifos-oxon, indicating the effect was not unique to diazinon. The oxon-induced augmentation of firing was blocked by the nicotinic acetylcholine receptor antagonist mecamylamine and the AMPA/kainate glutamate receptor antagonist DNQX. Together these data indicate that 1) acute OP exposure inhibits DRN cholinesterase, leading to acetylcholine accumulation, 2) the acetylcholine activates nicotinic receptors on 5-HT neurones and also on glutamatergic neurones, thus releasing glutamate and activating 5-HT neuronal AMPA/kainate receptors 3) the increase in 5-HT neuronal activity, and resulting 5-HT release, may lead to 5-HT1A autoreceptor down-regulation. This mechanism may be involved in the reported increase in risk of developing anxiety and depression following occupational OP exposure. PMID

  15. Central Nervous System Viral Invasion and Inflammation During Acute HIV Infection

    PubMed Central

    Valcour, Victor; Chalermchai, Thep; Sailasuta, Napapon; Marovich, Mary; Lerdlum, Sukalaya; Suttichom, Duanghathai; Suwanwela, Nijasri C.; Jagodzinski, Linda; Michael, Nelson; Spudich, Serena; van Griensven, Frits; de Souza, Mark; Kim, Jerome; Ananworanich, Jintanat

    2012-01-01

    Background. Understanding the earliest central nervous system (CNS) events during human immunodeficiency virus (HIV) infection is crucial to knowledge of neuropathogenesis, but these have not previously been described in humans. Methods. Twenty individuals who had acute HIV infection (Fiebig stages I-IV), with average 15 days after exposure, underwent clinical neurological, cerebrospinal fluid (CSF), magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) characterization. Results. HIV RNA was detected in the CSF from 15 of 18 subjects as early as 8 days after estimated HIV transmission. Undetectable CSF levels of HIV (in 3 of 18) was noted during Fiebig stages I, II, and III, with plasma HIV RNA levels of 285 651, 2321, and 81 978 copies/mL, respectively. On average, the CSF HIV RNA level was 2.42 log10 copies/mL lower than that in plasma. There were no cases in which the CSF HIV RNA level exceeded that in plasma. Headache was common during the acute retroviral syndrome (in 11 of 20 subjects), but no other neurological signs or symptoms were seen. Intrathecal immune activation was identified in some subjects with elevated CSF neopterin, monocyte chemotactic protein/CCL2, and interferon γ–induced protein 10/CXCL-10 levels. Brain inflammation was suggested by MRS. Conclusions. CSF HIV RNA was detectable in humans as early as 8 days after exposure. CNS inflammation was apparent by CSF analysis and MRS in some individuals during acute HIV infection. PMID:22551810

  16. Neonatal herpes simplex virus type-1 central nervous system disease with acute retinal necrosis.

    PubMed

    Fong, Choong Yi; Aye, Aye Mya Min; Peyman, Mohammadreza; Nor, Norazlin Kamal; Visvaraja, Subrayan; Tajunisah, Iqbal; Ong, Lai Choo

    2014-04-01

    We report a case of neonatal herpes simplex virus (HSV)-1 central nervous system disease with bilateral acute retinal necrosis (ARN). An infant was presented at 17 days of age with focal seizures. Cerebrospinal fluid polymerase chain reaction was positive for HSV-1 and brain magnetic resonance imaging showed cerebritis. While receiving intravenous acyclovir therapy, the infant developed ARN with vitreous fluid polymerase chain reaction positive for HSV-1 necessitating intravitreal foscarnet therapy. This is the first reported neonatal ARN secondary to HSV-1 and the first ARN case presenting without external ocular or cutaneous signs. Our report highlights that infants with neonatal HSV central nervous system disease should undergo a thorough ophthalmological evaluation to facilitate prompt diagnosis and immediate treatment of this rapidly progressive sight-threatening disease. PMID:24378951

  17. MEDUSA: a fuzzy expert system for medical diagnosis of acute abdominal pain.

    PubMed

    Fathi-Torbaghan, M; Meyer, D

    1994-12-01

    Even today, the diagnosis of acute abdominal pain represents a serious clinical problem. The medical knowledge in this field is characterized by uncertainty, imprecision and vagueness. This situation lends itself especially to be solved by the application of fuzzy logic. A fuzzy logic-based expert system for diagnostic decision support is presented (MEDUSA). The representation and application of uncertain and imprecise knowledge is realized by fuzzy sets and fuzzy relations. The hybrid concept of the system enables the integration of rule-based, heuristic and case-based reasoning on the basis of imprecise information. The central idea of the integration is to use case-based reasoning for the management of special cases, and rule-based reasoning for the representation of normal cases. The heuristic principle is ideally suited for making uncertain, hypothetical inferences on the basis of fuzzy data and fuzzy relations. PMID:7869951

  18. FloTrac/Vigileo system monitoring in acute-care surgery: current and future trends.

    PubMed

    Tsai, Yung-Fong; Liu, Fu-Chao; Yu, Huang-Ping

    2013-11-01

    As acute critical-care surgery evolves, it is imperative to introduce reliable devices that can intraoperatively assess a patient's cardiovascular functions. Owing to the fact that traditional methods are usually invasive, non- or less-invasive innovations have attracted the attention of clinicians in recent decades. The FloTrac system monitors cardiovascular performance by analyzing peripheral arterial waveforms and a preset database, and it decreases the invasiveness by using a pulmonary arterial catheter. The reliability of cardiac output measurements was confirmed in many critically ill subjects in cardiac surgeries and intensive care units. Moreover, the FloTrac system is easy to set up, and interpreting the information is simple. The FloTrac system also provides a useful preload predictor, that is, stroke volume variation (SVV), for fluid management, which has been proven to enhance surgical safety in the treatment of critically ill patients. Goal-directed therapy guided by SVV and other hemodynamic variables was advocated for peri-operative fluid optimization. Although the evolution of each updated algorithm of the FloTrac system has demonstrated improved accuracy and limited shortcomings, the latest third-generation algorithm is still not equal to the gold standard reference. The accuracy of the latest third-generation algorithm is controversial in septic conditions, and its use is still unacceptable in liver transplantation. Due to vasoactive challenges, especially in the administration of norepinephrine, a conclusion could not be reached. Clinicians should recognize the appropriate uses and limitations when using the algorithm during acute critical surgeries. PMID:24147549

  19. 76 FR 39883 - Design of Clinical Trials for Systemic Antibacterial Drugs for the Treatment of Acute Otitis...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-07

    ... HUMAN SERVICES Food and Drug Administration Design of Clinical Trials for Systemic Antibacterial Drugs... workshop regarding the design of Clinical Trials for Systemic Antibacterial Agents for the Treatment of... of clinical trials of antibacterial agents for the treatment of acute otitis media (middle...

  20. Photoprotective effect and acute oral systemic toxicity evaluation of the novel heterocyclic compound LQFM048.

    PubMed

    Vinhal, Daniela C; de Ávila, Renato Ivan; Vieira, Marcelo S; Luzin, Rangel M; Quintino, Michelle P; Nunes, Liliane M; Ribeiro, Antonio Carlos Chaves; de Camargo, Henrique Santiago; Pinto, Angelo C; Dos Santos Júnior, Helvécio M; Chiari, Bruna G; Isaac, Vera; Valadares, Marize C; Martins, Tatiana Duque; Lião, Luciano M; de S Gil, Eric; Menegatti, Ricardo

    2016-08-01

    The new heterocyclic derivative LQFM048 (3) (2,4,6-tris ((E)-ethyl 2-cyano-3-(4-hydroxy-3-methoxyphenyl)acrylate)-1,3,5-triazine) was originally designed through the molecular hybridization strategy from Uvinul® T 150 (1) and (E)-ethyl 2-cyano-3-(4hydroxy-3-methoxyphenyl)acrylate (2) sunscreens, using green chemistry approach. This compound was obtained in global yields (80%) and showed an interesting redox potential. In addition, it is thermally stable up to temperatures around 250°C. It was observed that LQFM048 (3) showed a low degradation after 150min of sunlight exposure at 39°C, whereas the extreme radiation conditions induced a considerable photodegradation of the LQFM048 (3), especially when irradiated by VIS and VIS+UVA. During the determination of sun protection factor, LQFM048 (3) showed interesting results, specially as in association with other photoprotective compounds and commercial sunscreen. Additionally, the compound (3) did not promote cytotoxicity for 3T3 fibroblasts. Moreover, it was not able to trigger acute oral systemic toxicity in mice, being classified as a compound with low acute toxicity hazard (2.000mg/kg>LD50<5.000mg/kg). Therefore, this compound synthesized using green chemistry approach is promising showing potential to development of a new sunscreen product with advantage of presenting redox potential, indicating antioxidant properties. PMID:27208746

  1. Systemic Lupus Erythematosus With Acute Inflammatory Demyelinating Polyneuropathy: A Case Report and Review of the Literature

    PubMed Central

    Li, Xiangling; Wang, Yanqiang

    2016-01-01

    We recently encountered a patient with acute inflammatory demyelinating polyneuropathy (AIDP) that was associated with systemic lupus erythematosus (SLE). A 34-year-old Chinese female with a 3-year history of SLE presented with acute bilateral leg weakness and paraparesis, and lost the ability to walk 1 day after noticing bilateral leg numbness and pain for 12 days. Physical examination revealed bilateral facial muscle paralysis, muscle strength in the legs with graded 1/5 proximally and 2/5 distally bilaterally and absence of deep tendon reflex in both knees and ankles. Paresthesia was observed in distal limbs with glove and stocking distribution. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation. Electrophysiologic survey also indicated sensory-motor demyelinating polyneuropathy. The diagnosis of SLE was established based on her initial symptoms including intermittent fevers, hair loss, oral ulcers, malar rash and arthritis affecting the elbow, wrist and hand joints; positive immunologic findings for antinuclear antibody (ANA), anti-DNA antibody, anti-Smith (anti-Sm) antibody, low serum complement levels, and the kidney biopsy specimen showed glomerular mesangial proliferation with focal endothelial cell proliferation (ISN/PPS 2004 classification lupus nephritis, class III). Treatment with intravenous immunoglobulin, methylprednisolone and cyclophosphamide resulted in clinical and electrophysiological improvement. PMID:27298667

  2. Evaluation of the acute cardiac and central nervous system effects of the fluorocarbon trifluoromethane in baboons

    SciTech Connect

    Branch, C.A.; Goldberg, D.A.; Ewing, J.R.; Butt, S.S.; Gayner, J.; Fagan, S.C.

    1994-12-31

    The gaseous fluorocarbon trifluoromethane has recently been investigated for its potential as an in vivo gaseous indicator for nuclear magnetic resonance studies of brain perfusion. Trifluoromethane may also have significant value as a replacement for chlorofluorocarbon fire retardants. Because of possible species-specific cardiotoxic and anesthetic properties, the toxicological evaluation of trifluoromethane in primates (Papio anubis) is necessary prior to its evaluation in humans. We report the acute cardiac and central nervous system effects of trifluoromethane in eight anesthetized baboons. A dose-response effect was established for respiratory rate, electroencephalogram, and cardiac sinus rate, which exhibited a stepwise decrease from 10% trifluoromethane. No spontaneous arrhythmias were noted, and arterial blood pressure remained unchanged at any inspired level. Intravenous epinephrine infusions (1 {mu}g/kg) induced transient cardiac arrhythmia in 1 animal only at 70% FC-23 (v/v) trifluoromethane. Trifluoromethane appears to induce mild dose-related physiological changes at inspired levels of 30% or more, indicative of an anesthetic effect. These data suggest that trifluoromethane may be safe to use in humans, without significant adverse acute effects, at an inspired level of 30%. 23 refs., 3 figs., 3 tabs.

  3. Acute phase treatment of venous thromboembolism: advanced therapy. Systemic fibrinolysis and pharmacomechanical therapy.

    PubMed

    Konstantinides, Stavros V; Wärntges, Simone

    2015-06-01

    Venous thromboembolism, which encompasses deep-vein thrombosis and acute pulmonary embolism (PE), represents a major contributor to global disease burden worldwide. For patients who present with cardiogenic shock or persistent hypotension (acute high-risk PE), there is consensus that immediate reperfusion treatment applying systemic fibrinolysis or, in the case of a high bleeding risk, surgical or catheter-directed techniques, is indicated. On the other hand, for the large, heterogeneous group of patients presenting without overt haemodynamic instability, the indications for advanced therapy are less clear. The recently updated guidelines of the European Society of Cardiology emphasise the importance of clinical prediction rules in combination with imaging procedures (assessment of right ventricular function) and laboratory biomarkers (indicative of myocardial stress or injury) for distinguishing between an intermediate and a low risk for an adverse early outcome. In intermediate-high-risk PE defined by the presence of both right ventricular dysfunction on echocardiography (or computed tomography) and a positive troponin (or natriuretic peptide) test, the bleeding risks of full-dose fibrinolytic treatment have been shown to outweigh its potential clinical benefits unless clinical signs of haemodynamic decompensation appear (rescue fibrinolysis). Recently published trials suggest that catheter-directed, ultrasound-assisted, low-dose local fibrinolysis may provide an effective and particularly safe treatment option for some of these patients. PMID:25789580

  4. Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

    2016-01-01

    Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

  5. Critical role for the AIM2 inflammasome during acute central nervous system bacterial infection

    PubMed Central

    Hanamsagar, Richa; Aldrich, Amy; Kielian, Tammy

    2014-01-01

    Interleukin-1β (IL-1β) is essential for eliciting protective immunity during the acute phase of Staphylococcus aureus (S. aureus) infection in the central nervous system (CNS). We previously demonstrated that microglial IL-1β production in response to live S. aureus is mediated through the Nod-like receptor protein 3 (NLRP3) inflammasome, including the adapter protein ASC (apoptosis-associated, speck-like, caspase-1 recruiting domain-containing protein), and pro-caspase-1. Here we utilized NLRP3, ASC, and caspase-1/11 knockout (KO) mice to demonstrate the functional significance of inflammasome activity during CNS S. aureus infection. ASC and caspase-1/11 KO animals were exquisitely sensitive, with approximately 50% of mice succumbing to infection within 24 h. Unexpectedly, the survival of NLRP3 KO mice was similar to WT animals, suggesting the involvement of an alternative upstream sensor, which was later identified as absent in melanoma 2 (AIM2) based on the similar disease patterns between AIM2 and ASC KO mice. Besides IL-1β, other key inflammatory mediators, including IL-6, CXCL1, CXCL10, and CCL2 were significantly reduced in the CNS of AIM2 and ASC KO mice, implicating autocrine/paracrine actions of IL-1β, since these mediators do not require inflammasome processing for secretion. These studies demonstrate a novel role for the AIM2 inflammasome as a critical molecular platform for regulating IL-1β release and survival during acute CNS S. aureus infection. PMID:24484406

  6. Systemic amyloidosis involving the diaphragm and acute massive hydrothorax during peritoneal dialysis.

    PubMed

    Gagnon, R F; Thirlweil, M; Arzoumanian, A; Mehio, A

    2002-06-01

    Hydrothorax secondary to trans-diaphragmatic fluid leakage through a peritoneo-pleural communication is an occasional, potentially serious complication of peritoneal dialysis. The etiology of this condition is not clear, being thought to be due either to congenital or acquired diaphragmatic fenestrations or acquired scarcity of muscle fibers in the tendinous part of the diaphragm which are compounded by increased intra-abdominal pressure during the dwell period of peritoneal dialysis. We report a 54-year-old woman who developed irreversible acute renal failure from adjuvant chemotherapy for ovarian cancer previously resected surgically. Three days after the onset of continuous ambulatory peritoneal dialysis, she developed acute respiratory distress associated with a massive right hydrothorax secondary to a peritoneo-pleural communication demonstrated by scintigraphy. At autopsy 2 weeks later, systemic amyloidosis was surprisingly found and histologic examination of the right hemidiaphragm showed the presence of amyloid, among sparse muscle fibers. This is the first case report of a distinct pathological process, i.e. amyloidosis, involving the diaphragm associated with a peritoneo-pleural communication causing massive hydrothorax at the onset of peritoneal dialysis. PMID:12078953

  7. Systemic Lupus Erythematosus With Acute Inflammatory Demyelinating Polyneuropathy: A Case Report and Review of the Literature.

    PubMed

    Li, Xiangling; Wang, Yanqiang

    2016-07-01

    We recently encountered a patient with acute inflammatory demyelinating polyneuropathy (AIDP) that was associated with systemic lupus erythematosus (SLE). A 34-year-old Chinese female with a 3-year history of SLE presented with acute bilateral leg weakness and paraparesis, and lost the ability to walk 1 day after noticing bilateral leg numbness and pain for 12 days. Physical examination revealed bilateral facial muscle paralysis, muscle strength in the legs with graded 1/5 proximally and 2/5 distally bilaterally and absence of deep tendon reflex in both knees and ankles. Paresthesia was observed in distal limbs with glove and stocking distribution. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation. Electrophysiologic survey also indicated sensory-motor demyelinating polyneuropathy. The diagnosis of SLE was established based on her initial symptoms including intermittent fevers, hair loss, oral ulcers, malar rash and arthritis affecting the elbow, wrist and hand joints; positive immunologic findings for antinuclear antibody (ANA), anti-DNA antibody, anti-Smith (anti-Sm) antibody, low serum complement levels, and the kidney biopsy specimen showed glomerular mesangial proliferation with focal endothelial cell proliferation (ISN/PPS 2004 classification lupus nephritis, class III). Treatment with intravenous immunoglobulin, methylprednisolone and cyclophosphamide resulted in clinical and electrophysiological improvement. PMID:27298667

  8. Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

    SciTech Connect

    Buehler, Paul W.; Butt, Omer I.; D'Agnillo, Felice

    2011-06-10

    Highlights: {yields} Toxicological implications associated with the use of NaNO{sub 2} therapy to treat systemic cell-free Hb exposure are not well-defined. {yields} Systemic Hb exposure followed by NaNO{sub 2} infusion induces acute CNS toxicities in guinea pigs. {yields} These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO{sub 2} alone. {yields} NaNO{sub 2}-mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO{sub 2}) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO{sub 2} with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO{sub 2} on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO{sub 2}, at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO{sub 2} alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

  9. A Microfluidic Device for Continuous Sensing of Systemic Acute Toxicants in Drinking Water

    PubMed Central

    Zhao, Xinyan; Dong, Tao

    2013-01-01

    A bioluminescent-cell-based microfluidic device for sensing toxicants in drinking water was designed and fabricated. The system employed Vibrio fischeri cells as broad-spectrum sensors to monitor potential systemic cell toxicants in water, such as heavy metal ions and phenol. Specifically, the chip was designed for continuous detection. The chip design included two counter-flow micromixers, a T-junction droplet generator and six spiral microchannels. The cell suspension and water sample were introduced into the micromixers and dispersed into droplets in the air flow. This guaranteed sufficient oxygen supply for the cell sensors. Copper (Cu2+), zinc (Zn2+), potassium dichromate and 3,5-dichlorophenol were selected as typical toxicants to validate the sensing system. Preliminary tests verified that the system was an effective screening tool for acute toxicants although it could not recognize or quantify specific toxicants. A distinct non-linear relationship was observed between the zinc ion concentration and the Relative Luminescence Units (RLU) obtained during testing. Thus, the concentration of simple toxic chemicals in water can be roughly estimated by this system. The proposed device shows great promise for an early warning system for water safety. PMID:24300075

  10. Exposure to welding fumes is associated with acute systemic inflammatory responses

    PubMed Central

    Kim, J; Chen, J; Boyce, P; Christiani, D

    2005-01-01

    Aims: To investigate the acute systemic inflammatory response to welding fume exposure. Methods: Twenty four welders (42% smokers) and 13 non-exposed controls (23% smokers) were monitored at a welding school. Exposure to fine particulate matter (PM2.5) was assessed using cyclone samplers. Markers of systemic inflammation, including C-reactive protein (CRP), fibrinogen, and white blood cell (WBC) levels, were determined in peripheral blood samples collected at baseline and after 5.3 (SD 1.0) hours of exposure. Results: The median PM2.5 concentration for welders was 1.66 mg/m3, which was significantly greater than that for controls (0.04 mg/m3). Compared to non-smokers, smokers had a significantly higher baseline WBC count, but comparable levels of CRP and fibrinogen. In non-smokers, welding fume exposure was associated with a significant increase in WBC and neutrophil counts immediately following exposure (+0.8x103/µl, 95% CI 0.1 to 1.6, and +1.0x103/µl, 95% CI 0.4 to 1.7, respectively). A significant decrease in fibrinogen levels was observed in non-smokers (–32 mg/dl, 95% CI –63 to –1). No significant changes in WBC, neutrophil, and fibrinogen levels were found in smokers. Sixteen hours after welding exposure, CRP levels were found to be significantly increased in both non-smokers and smokers (0.90 mg/l, 95% CI 0.17 to 1.64). PM2.5 concentrations were found to be significantly associated with absolute neutrophil counts in non-smokers, and CRP levels in both non-smokers and smokers. Conclusions: High levels of welding fume exposure induce acute systemic inflammation in a relatively young, healthy working population. These results also suggest that smoking may modify the effect of welding fume exposure on specific inflammatory markers. PMID:15723880

  11. Transcatheter Mitral Valve Repair in Surgical High-Risk Patients: Gender-Specific Acute and Long-Term Outcomes

    PubMed Central

    Tigges, Eike; Kalbacher, Daniel; Thomas, Christina; Appelbaum, Sebastian; Deuschl, Florian; Schofer, Niklas; Schlüter, Michael; Conradi, Lenard; Schirmer, Johannes; Treede, Hendrik; Reichenspurner, Hermann; Blankenberg, Stefan; Schäfer, Ulrich; Lubos, Edith

    2016-01-01

    Background. Analyses emphasizing gender-related differences in acute and long-term outcomes following MitraClip therapy for significant mitral regurgitation (MR) are rare. Methods. 592 consecutive patients (75 ± 8.7 years, 362 men, 230 women) underwent clinical and echocardiographic follow-up for a median of 2.13 (0.99–4.02) years. Results. Significantly higher prevalence of cardiovascular comorbidities, renal failure, and adverse echocardiographic parameters in men resulted in longer device time (p = 0.007) and higher numbers of implanted clips (p = 0.0075), with equal procedural success (p = 1.0). Rehospitalization for heart failure did not differ (p[logrank] = 0.288) while survival was higher in women (p[logrank] = 0.0317). Logarithmic increase of NT-proBNP was a common independent predictor of death. Hypercholesterolemia and peripheral artery disease were predictors of death only in men while ischemic and dilative cardiomyopathy (CM) and age were predictors in women. Independent predictors of rehospitalization for heart failure were severely reduced ejection fraction and success in men while both ischemic and dilative CM, logistic EuroSCORE, and MR severity were predictive in women. Conclusions. Higher numbers of implanted clips and longer device time are likely related to more comorbidities in men. Procedural success and acute and mid-term clinical outcomes were equal. Superior survival for women in long-term analysis is presumably attributable to a comparatively better preprocedural health. PMID:27042662

  12. Trypanosoma cruzi Entrance through Systemic or Mucosal Infection Sites Differentially Modulates Regional Immune Response Following Acute Infection in Mice

    PubMed Central

    de Meis, Juliana; Barreto de Albuquerque, Juliana; Silva dos Santos, Danielle; Farias-de-Oliveira, Désio Aurélio; Berbert, Luiz Ricardo; Cotta-de-Almeida, Vinícius; Savino, Wilson

    2013-01-01

    Acute Chagas disease is characterized by a systemic infection that leads to the strong activation of the adaptive immune response. Outbreaks of oral contamination by the infective protozoan Trypanosoma cruzi are frequent in Brazil and other Latin American countries, and an increased severity of clinical manifestations and mortality is observed in infected patients. These findings have elicited questions about the specific responses triggered after T. cruzi entry via mucosal sites, possibly modulating local immune mechanisms, and further impacting regional and systemic immunity. Here, we provide evidence for the existence of differential lymphoid organ responses in experimental models of acute T. cruzi infection. PMID:23898334

  13. A compact and autoclavable system for acute extracellular neural recording and brain pressure monitoring for humans.

    PubMed

    Angotzi, Gian Nicola; Baranauskas, Gytis; Vato, Alessandro; Bonfanti, Andrea; Zambra, Guido; Maggiolini, Emma; Semprini, Marianna; Ricci, Davide; Ansaldo, Alberto; Castagnola, Elisa; Ius, Tamara; Skrap, Miran; Fadiga, Luciano

    2015-02-01

    One of the most difficult tasks for the surgeon during the removal of low-grade gliomas is to identify as precisely as possible the borders between functional and non-functional brain tissue with the aim of obtaining the maximal possible resection which allows to the patient the longer survival. For this purpose, systems for acute extracellular recordings of single neuron and multi-unit activity are considered promising. Here we describe a system to be used with 16 microelectrodes arrays that consists of an autoclavable headstage, a built-in inserter for precise electrode positioning and a system that measures and controls the pressure exerted by the headstage on the brain with a twofold purpose: to increase recording stability and to avoid disturbance of local perfusion which would cause a degradation of the quality of the recording and, eventually, local ischemia. With respect to devices where only electrodes are autoclavable, our design permits the reduction of noise arising from long cable connections preserving at the same time the flexibility and avoiding long-lasting gas sterilization procedures. Finally, size is much smaller and set up time much shorter compared to commercial systems currently in use in surgery rooms, making it easy to consider our system very useful for intra-operatory mapping operations. PMID:25486648

  14. Acute Changes in Peripheral Vascular Tonus and Systemic Circulation during Static Stretching.

    PubMed

    Inami, Takayuki; Baba, Reizo; Nakagaki, Akemi; Shimizu, Takuya

    2015-01-01

    This study aimed to investigate the acute effect of static stretching (SS) on peripheral vascular tonus and to clarify the effect of SS on systemic circulation. Twenty healthy young male volunteers performed a 1-min SS motion of the right triceps surae muscle, repeated five times. The peripheral vascular tonus (|d/a| ratio) was obtained using second derivatives of the photoplethysmogram readings before, during, and after SS. Heart rate and blood pressure (BP) were also measured. The |d/a| ratio and BP were transiently, but significantly, elevated during SS and returned to baseline immediately after SS. Furthermore, we observed a significant correlation between the amount of change in the |d/a| ratio and the ankle range of motion during SS (r = 0.793 to 0.832, P = 0.01). These responses may be caused by mechanical stress during SS. PMID:25833293

  15. Acute systemic hypotension after arteriovenous fistula construction in a patient with severe aortic stenosis.

    PubMed

    Mise, Naobumi; Uchida, Lisa; Tanaka, Mototsugu; Tanaka, Shinji; Nakajima, Hiroyoshi; Sugimoto, Tokuichiro

    2011-10-01

    We report the case of a 53-year-old hemodialysis patient with severe aortic stenosis, who developed acute systemic hypoperfusion after arteriovenous fistula (AVF) construction. He presented with hypotension and repeated syncope soon after distal radiocephalic AVF construction, and finally developed a respiratory arrest. His blood pressure and hemodynamics recovered promptly by sub-emergent aortic valve replacement surgery. In the present case, the heart with severe aortic stenosis could not increase cardiac output in response to the reduction in peripheral vascular resistance caused by the AVF. High-output heart failure, a relatively rare AVF-associated disorder, occurs with an excessive AVF flow, usually more than 3 L/min or 30% of cardiac output. However, heart failure may develop soon after construction of an AVF with a moderate blood flow if a patient's cardiac function is severely impaired. In addition, heart failure may improve with AVF preservation if the underlying heart disease is treatable. PMID:21725657

  16. Molecular Analysis of Central Nervous System Disease Spectrum in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Hicks, Chindo; Sitthi-Amorn, Jitsuda; Douglas, Jessica; Ramani, Ritika; Miele, Lucio; Vijayakumar, Vani; Karlson, Cynthia; Chipeta, James; Megason, Gail

    2016-01-01

    Treatment of the central nervous system (CNS) is an essential therapeutic component in childhood acute lymphoblastic leukemia (ALL). The goal of this study was to identify molecular signatures distinguishing patients with CNS disease from those without the disease in pediatric patients with ALL. We analyzed gene expression data from 207 pediatric patients with ALL. Patients without CNS were classified as CNS1, while those with mild and advanced CNS disease were classified as CNS2 and CNS3, respectively. We compared gene expression levels among the three disease classes. We identified gene signatures distinguishing the three disease classes. Pathway analysis revealed molecular networks and biological pathways dysregulated in response to CNS disease involvement. The identified pathways included the ILK, WNT, B-cell receptor, AMPK, ERK5, and JAK signaling pathways. The results demonstrate that transcription profiling could be used to stratify patients to guide therapeutic decision-making in pediatric ALL. PMID:26997880

  17. All arthroscopic stabilization of acute acromioclavicular joint dislocation with fiberwire and endobutton system

    PubMed Central

    Spoliti, Marco; De Cupis, Mauro; Via, Alessio Giai; Oliva, Francesco

    2014-01-01

    Summary Introduction: acromioclavicular (AC) joint dislocation is common in athletes and in contact sports and about 9% of shoulder injuries involves this joint. The majority of these AC lesions can be successfully treated conservatively but high grade dislocation and some cases of type III dislocation need a surgical treatment. Many different operative techniques have been described over the years. The purpose of this study is to evaluate the results of arthroscopic stabilization of AC joint dislocation with TightRope® system. Materials and methods: nineteen patients with acute AC dislocation were treated by arthroscopic fixation with TightRope® system. Any associated lesions were repaired. All patients were assessed before surgery (T0), at 3 months (T1), at 6 months (T2) and at 1 year after the surgery (T3) using a visual analogic scale (VAS) and Constant-Murley Score (CMS). All patients were evaluated with X-ray. Results: six AC-joint dislocations involved the right shoulder and thirteen the left shoulder. Ten were type III dislocation, three were type IV and six were type V dislocation. We found a statistically significant reduction of pain (p< 0.01) at T1 compared to the pretreatment scores. The CMS measures showed an improvement between T1, T2 and T3, but the difference was statistically significant only between T1 and T3 (p= 0.017). The postoperative X-Ray of the shoulder showed a good reduction of the AC joint dislocation. We had 1 case of recurrence and 2 cases of loss of intraoperative reduction. Conclusion: arthroscopic technique for acute AC joint dislocations with the use of the TightRope® device is minimally invasive and it allows an anatomic restoration of the joint. It is a safe and effective procedure ensuring stable AC joint reconstruction and good cosmetic results. PMID:25767774

  18. Mechanism for the acute effects of organophosphate pesticides on the adult 5-HT system

    PubMed Central

    Judge, Sarah J.; Savy, Claire Y.; Campbell, Matthew; Dodds, Rebecca; Gomes, Larissa Kruger; Laws, Grace; Watson, Anna; Blain, Peter G.; Morris, Christopher M.; Gartside, Sarah E.

    2016-01-01

    The neurotransmitter serotonin (5-HT) is involved in mood disorder aetiology and it has been reported that (organophosphate) OP exposure affects 5-HT turnover. The aim of this study was to elucidate the mechanism underlying OP effects on the adult 5-HT system. First, acute in vivo administration of the OP diazinon (0, 1.3, 13 or 39 mg/kg i.p.) to male Hooded Lister rats inhibited the activity of the cholinergic enzyme acetylcholinesterase in blood and in the hippocampus, dorsal raphe nucleus (DRN), striatum and prefrontal cortex. Diazinon-induced cholinesterase inhibition was greatest in the DRN, the brain's major source of 5-HT neurones. Second, acute in vivo diazinon exposure (0 or 39 mg/kg i.p.) increased the basal firing rate of DRN neurones measured ex vivo in brain slices. The excitatory responses of DRN neurones to α1-adrenoceptor or AMPA/kainate receptor activation were not affected by in vivo diazinon exposure but the inhibitory response to 5-HT was attenuated, indicating 5-HT1A autoreceptor down-regulation. Finally, direct application of the diazinon metabolite diazinon oxon to naive rat brain slices increased the firing rate of DRN 5-HT neurones, as did chlorpyrifos-oxon, indicating the effect was not unique to diazinon. The oxon-induced augmentation of firing was blocked by the nicotinic acetylcholine receptor antagonist mecamylamine and the AMPA/kainate glutamate receptor antagonist DNQX. Together these data indicate that 1) acute OP exposure inhibits DRN cholinesterase, leading to acetylcholine accumulation, 2) the acetylcholine activates nicotinic receptors on 5-HT neurones and also on glutamatergic neurones, thus releasing glutamate and activating 5-HT neuronal AMPA/kainate receptors 3) the increase in 5-HT neuronal activity, and resulting 5-HT release, may lead to 5-HT1A autoreceptor down-regulation. This mechanism may be involved in the reported increase in risk of developing anxiety and depression following occupational OP exposure. PMID

  19. Exploring the Relationships between the Electronic Health Record System Components and Patient Outcomes in an Acute Hospital Setting

    ERIC Educational Resources Information Center

    Wiggley, Shirley L.

    2011-01-01

    Purpose: The purpose of this study was to examine the relationship between the electronic health record system components and patient outcomes in an acute hospital setting, given that the current presidential administration has earmarked nearly $50 billion to the implementation of the electronic health record. The relationship between the…

  20. 77 FR 43089 - Evaluation of an Up-and-Down Procedure for Acute Dermal Systemic Toxicity Testing: Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-23

    ... (NICEATM), in collaboration with the Interagency Coordinating Committee on the Validation of Alternative... validation status of an up-and-down procedure (UDP) for acute dermal systemic toxicity testing. NICEATM... Panel and made available to the public. The Panel will meet in public session to review the...

  1. Mesotherapy versus Systemic Therapy in the Treatment of Acute Low Back Pain: A Randomized Trial.

    PubMed

    Costantino, Cosimo; Marangio, Emilio; Coruzzi, Gabriella

    2011-01-01

    Pharmacological therapy of back pain with analgesics and anti-inflammatory drugs is frequently associated with adverse effects, particularly in the elderly. Aim of this study was to compare mesotherapic versus conventional systemic administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids in patients with acute low back pain. Eighty-four patients were randomized to receive anti-inflammatory therapy according to the following protocols: (a) mesotherapy group received the 1st and 4th day 2% lidocaine (1 mL) + ketoprofen 160 mg (1 mL) + methylprednisolone 40 mg (1 mL), then on 7th, 10th, and 13th day, 2% lidocaine (1 mL) + ketoprofen 160 mg (1 mL) + methylprednisolone 20 mg (1 mL) (b) conventional therapy group received ketoprofen 80 mg × 2/die and esomeprazole 20 mg/die orally for 12 days, methylprednisolone 40 mg/die intramuscularly for 4 days, followed by methylprednisolone 20 mg/die for 3 days, and thereafter, methylprednisolone 20 mg/die at alternate days. Pain intensity and functional disability were assessed at baseline (T0), at the end of treatment (T1), and 6 months thereafter (T2) by using visual analogic scale (VAS) and Roland-Morris disability questionnaire (RMDQ). In both groups, VAS and RMDQ values were significantly reduced at the end of drug treatment and after 6 months, in comparison with baseline. No significant differences were found between the two groups. This suggests that mesotherapy may be a valid alternative to conventional therapy in the treatment of acute low back pain with corticosteroids and NSAIDs. PMID:20953425

  2. Adrenocorticotropic hormone in serial cerebrospinal fluid in man - Subject to acute regulation by the hypothalamic-pituitary-adrenocortical system?

    PubMed

    Kellner, Michael; Wortmann, Viola; Salzwedel, Cornelie; Kober, Daniel; Petzoldt, Martin; Urbanowicz, Tatiana; Pulic, Mersija; Boelmans, Kai; Yassouridis, Alexander; Wiedemann, Klaus

    2016-05-30

    Acute regulation of adrenocorticotropic hormone (ACTH) in cerebrospinal fluid (CSF) by the hypothalamic-pituitary-adrenocortical system has not been investigated in man. In a pilot study in healthy male volunteers we measured ACTH every twenty minutes in serial CSF for three hours after an intravenous placebo, hydrocortisone (100mg) or insulin (2mg/kg) injection. No acute inhibitory or stimulatory effects of these interventions were discovered. Our results corroborate previous findings in rhesus monkeys. The regulation of CSF ACTH and its potential relevance for behavioral alterations in health and disease (e.g. major depression or anorexia nervosa) in humans need further study. PMID:27031591

  3. [Influence of cortical neurotrophic factors on the neurocytokine production system in acute hemorrhagic stroke].

    PubMed

    Kul'chikov, A E; Kositsyn, N S; Svinov, M M; Vasil'eva, I G; Makarenko, A N

    2009-01-01

    The mechanism of therapeutic action of cortical neurotropic factors (CNTF) was studied in hemorrhagic stroke. In intracerebral hemorrhage, CNTFs were shown to elevate the level of nerve growth factor mRNA and at the same time, produce no effect on its level in intact animals. The neuroactivating action of CNTF in the acute phase of hemorrhagic stroke was achieved by intranasal administration due to the retrograde axon transport of CNTF molecules along the olfactory nerve fibers to the brain, by passing the blood-brain barrier. It was ascertained that the molecules of tritium-labeled CHTF accumulated in the central nervous system following 20 minutes and the level of label accumulation is proportionally increased after 120 minutes. The pattern of accumulation of the intranasally administered label in the olfactory tract and olfactory bulb proves CNTF transportation along these structures of the nervous system. Therefore, when intranasally administered, CNTFs are able to transport to the central nervous system along the olfactory tract and to enhance the expression of nerve growth factor mRNA in hemorrhagic stroke. PMID:19919011

  4. Central Nervous System Involvement in Adult Acute Lymphoblastic Leukemia: Diagnostic Tools, Prophylaxis, and Therapy

    PubMed Central

    Del Principe, Maria Ilaria; Maurillo, Luca; Buccisano, Francesco; Sconocchia, Giuseppe; Cefalo, Mariagiovanna; De Santis, Giovanna; Di Veroli, Ambra; Ditto, Concetta; Nasso, Daniela; Postorino, Massimiliano; Refrigeri, Marco; Attrotto, Cristina; Del Poeta, Giovanni; Lo-Coco, Francesco; Amadori, Sergio; Venditti, Adriano

    2014-01-01

    In adult patients with acute lymphoblastic leukemia (ALL), Central Nervous System (CNS) involvement is associated with a very poor prognosis. The diagnostic assessment of this condition relies on the use of neuroradiology, conventional cytology (CC) and flow cytometry (FCM). Among these approaches, which is the gold standard it is still a matter of debate. Neuroradiology and CC have a limited sensitivity with a higher rate of false negative results. FCM demonstrated a superior sensitivity over CC, particularly when low levels of CNS infiltrating cells are present. Although prospective studies of a large series of patients are still awaited, a positive finding by FCM appears to anticipate an adverse outcome even if CC shows no infiltration. Current strategies for adult ALL CNS-directed prophylaxis or therapy involve systemic and intrathecal chemotherapy and radiation therapy. An early and frequent intrathecal injection of cytostatic combined with systemic chemotherapy is the most effective strategy to reduce the frequency of CNS involvement. In patients with CNS overt ALL, at diagnosis or upon relapse, allogeneic hematopoietic stem cell transplantation might be considered. This review discusses risk factors, diagnostic techniques for identification of CNS infiltration and modalities of prophylaxis and therapy to manage it. PMID:25408861

  5. Changes in IgG and total plasma protein glycomes in acute systemic inflammation

    PubMed Central

    Novokmet, Mislav; Lukić, Edita; Vučković, Frano; –Durić, Željko; Keser, Toma; Rajšl, Katarina; Remondini, Daniel; Castellani, Gastone; Gašparović, Hrvoje; Gornik, Olga; Lauc, Gordan

    2014-01-01

    Recovery after cardiac surgery is a complex process that has to compensate for both individual variability and extensive tissue damage in the context of systemic inflammation. Protein glycosylation is essential in many steps of the inflammatory cascade, but due to technological limitations the role of individual variation in glycosylation in systemic inflammation has not been addressed until now. We analysed composition of the total plasma and IgG N-glycomes in 107 patients undergoing cardiac surgery. In nearly all individuals plasma N-glycome underwent the same pattern of changes in the first 72 h, revealing a general mechanism of glycosylation changes. To the contrary, changes in the IgG glycome were very individualized. Bi-clustering analysis revealed the existence of four distinct patterns of changes. One of them, characterized by a rapid increase in galactosylated glycoforms, was associated with nearly double mortality risk measured by EuroSCORE II. Our results indicate that individual variation in IgG glycosylation changes during acute systemic inflammation associates with increased mortality risk and indicates new avenues for the development of personalized diagnostic and therapeutic approach. PMID:24614541

  6. Experience with a Simplified Computer Based Intensive Care Monitoring System in the Management of Acutely Ill Surgical Patients

    PubMed Central

    Hadley, H. Roger; Rutherford, Harold G.; Smith, Louis L.; Briggs, Burton A.; Neilsen, Ivan R.; Rau, Richard

    1979-01-01

    The need exists for a simplified and ecomonical computer based monitoring system for critically ill surgical patients. Such a system would enjoy widespread use in surgical intensive care units in regional, as well as larger community hospitals. We have assembled such a system which provides digital readout of the usual physiologic parameters, and also provide computer storage of accumulated data for review and evaluation of patient care. The computer provides graphic and digital display and digital printout for subsequent inclusion in the patient records. Most frequent indications for this system include the development of acute respiratory insufficiency or acute circulatory failure due to invasive sepsis and/or severe arteriosclerotic cardiovascular disease. Information most beneficial in patient care included measurement of cardiac output;alveolar arterial oxygen gradient. ImagesFigure 1Figure 5Figure 9Figure 11

  7. Imaging of Acute Pancreatitis.

    PubMed

    Thoeni, Ruedi F

    2015-11-01

    Acute pancreatitis is an acute inflammation of the pancreas. Several classification systems have been used in the past but were considered unsatisfactory. A revised Atlanta classification of acute pancreatitis was published that assessed the clinical course and severity of disease; divided acute pancreatitis into interstitial edematous pancreatitis and necrotizing pancreatitis; discerned an early phase (first week) from a late phase (after the first week); and focused on systemic inflammatory response syndrome and organ failure. This article focuses on the revised classification of acute pancreatitis, with emphasis on imaging features, particularly on newly-termed fluid collections and implications for the radiologist. PMID:26526433

  8. Acute Resistance Exercise Induces Antinociception by Activation of the Endocannabinoid System in Rats

    PubMed Central

    Galdino, Giovane; Romero, Thiago; da Silva, José Felippe Pinho; Aguiar, Daniele; de Paula, Ana Maria; Cruz, Jader; Parrella, Cosimo; Piscitelli, Fabiana; Duarte, Igor; Di Marzo, Vincenzo; Perez, Andrea

    2014-01-01

    Background Resistance exercise (RE) is also known as strength training, and it is performed to increase the strength and mass of muscles, bone strength and metabolism. RE has been increasingly prescribed for pain relief. However, the endogenous mechanisms underlying this antinociceptive effect are still largely unexplored. Thus, we investigated the involvement of the endocannabinoid system in RE-induced antinociception. Methods Male Wistar rats were submitted to acute RE in a weight-lifting model. The nociceptive threshold was measured by a mechanical nociceptive test (paw pressure) before and after exercise. To investigate the involvement of cannabinoid receptors and endocannabinoids in RE-induced antinociception, cannabinoid receptor inverse agonists, endocannabinoid metabolizing enzyme inhibitors and an anandamide reuptake inhibitor were injected before RE. After RE, CB1 cannabinoid receptors were quantified in rat brain tissue by Western blot and immunofluorescence. In addition, endocannabinoid plasma levels were measured by isotope dilution-liquid chromatography mass spectrometry. Results RE-induced antinociception was prevented by preinjection with CB1 and CB2 cannabinoid receptor inverse agonists. By contrast, preadministration of metabolizing enzyme inhibitors and the anandamide reuptake inhibitor prolonged and enhanced this effect. RE also produced an increase in the expression and activation of CB1 cannabinoid receptors in rat brain tissue and in the dorsolateral and ventrolateral periaqueductal regions and an increase of endocannabinoid plasma levels. Conclusion The present study suggests that a single session of RE activates the endocannabinoid system to induce antinociception. PMID:24977916

  9. Acute Systemic Infusion of Bupropion Decrease Formalin Induced Pain Behavior in Rat

    PubMed Central

    Naderi, Somayyeh; Ashrafi Osalou, Mostafa; Cankurt, Ulker

    2014-01-01

    Background The chronic pain can disturb physical, psychological, and social performances. Analgesic agents are widely used but some antidepressants (ADs) showed analgesia also. Bupropion is using for smoke cessation but it can change morphine withdrawal signs such as pain. This study tested the acute systemic effect of bupropion on formalin induced pain behavior in rats. Methods Wistar male healthy rats were divided into 7 groups (control, sham, and 5 treated groups with 10, 30, 90, 120, and 200 mg/kg of bupropion, i.p.). The bupropion injected 3 hours prior to formalin induced pain behavior. Formalin (50 µl, 2.5%) was injected subcutaneously in dorsal region of right hindpaw in all animals. Nociceptive signs were observed continuously on-line and off-line each minute. Common pain scoring was used for pain assessment. Results The analysis of data by one-way ANOVA showed that bupropion can reduce pain scores in the second phase but not in first phase. Bupropion decreased the licking/biting duration significantly in first and second phase of formalin test. Conclusions The results showed that bupropion has analgesic effects at systemic application. The change of second phase of the pain behavior was significant and it revealed that central mechanisms involve in bupropion analgesia. PMID:24748939

  10. Central nervous system haemorrhage causing early death in acute promyelocytic leukaemia

    PubMed Central

    Borowska, Anna; Stelmaszczyk-Emmel, Anna

    2016-01-01

    Acute promyelocytic leukaemia (APL) is a rare type of paediatric leukaemia characterised by a specific genetic mutation and life-threatening coagulopathy. The discovery of all-trans retinoic acid (ATRA), which acts directly on promyelocytic locus-retinoic acid receptor α (PML-RARα) gene product, brought a revolution to the therapy of this disorder. Unfortunately, despite an improvement in the complete remission rate, the early death (ED) rate has not changed significantly, and the haemorrhages remain a major problem. The most common bleeding site, which accounts for about 65-80% of haemorrhages, is the central nervous system. Second in line are pulmonary haemorrhages (32%), while gastrointestinal bleedings are relatively rare. Haemorrhages result from thrombocytopaenia, disseminated intravascular coagulopathy (DIC), and systemic fibrinolysis. Herein we present a boy aged one year and nine months with APL. The patient was not eligible for ATRA administration due to poor clinical condition. He developed bleeding diathesis that presented as disseminated intravascular coagulation (DIC) and led to intracranial haemorrhage, which resulted in the patient's death. PMID:26862315

  11. Systemic response induced by Scorpaena plumieri fish venom initiates acute lung injury in mice.

    PubMed

    Boletini-Santos, Douglas; Komegae, Evilin Naname; Figueiredo, Suely G; Haddad, Vidal; Lopes-Ferreira, Mônica; Lima, Carla

    2008-03-15

    Scorpaena plumieri venomous fish inflicted severe injuries in humans characterized by systemic effects and cardiovascular abnormalities. Although cardiotoxic and hypotensive effects induced in rats by this venom have been studied, little is known about their effect on bronchial epithelial permeability and airway inflammation in mice. The primary goal of this study was to determine whether the intraplantar or intraperitoneal injection of S. plumieri venom results in systemic response, and whether this event initiates acute lung injury. We found that BALB/c mice developed neutrophilic infiltrates, areas of lung hemorrhage and alveolar macrophage activation within 24h after injection with S. plumieri venom. These histopathological changes were associated with an early increase in BAL fluid protein and early induction of cytokines, chemokines and matrix metalloproteinases, followed by a later increase in BAL fluid neutrophils. These findings provide clear evidence that the injection of S. plumieri venom in footpad or peritoneal cavity of mice results in venom deposition in the airway and initiates a sustained inflammatory response in the lungs. PMID:18191167

  12. Current Evidence for Extracorporeal Liver Support Systems in Acute Liver Failure and Acute-on-Chronic Liver Failure.

    PubMed

    Karvellas, Constantine J; Subramanian, Ram M

    2016-07-01

    Artificial (nonbiological) extracorporeal liver support devices aim to remove albumin-bound and water-soluble toxins to restore and preserve hepatic function and mitigate or limit the progression of multiorgan failure while hepatic recovery or liver transplant occurs. The following beneficial effects have been documented: improvement of jaundice, amelioration of hemodynamic instability, reduction of portal hypertension, and improvement of hepatic encephalopathy. The only randomized prospective multicenter controlled trial to show an improvement in transplant-free survival was for high-volume plasmapheresis. Biological (cell-based) extracorporeal liver support systems aim to support the failing liver through detoxification and synthetic function and warrant further study for safety and benefit. PMID:27339682

  13. Identification and Acute Targeting of Gaps in Atrial Ablation Lesion Sets using a Real Time MRI System

    PubMed Central

    Ranjan, Ravi; Kholmovski, Eugene G.; Blauer, Joshua; Vijayakumar, Sathya; Volland, Nelly A.; Salama, Mohamed E.; Parker, Dennis L.; MacLeod, Rob; Marrouche, Nassir F.

    2013-01-01

    Background Radiofrequency ablation is routinely used to treat cardiac arrhythmias, but gaps remain in ablation lesion sets, as there is no direct visualization of ablation related changes. In this study we describe using a real time MRI (RT-MRI) system to acutely identify and target gaps leading to a complete and transmural ablation in the atrium. Methods and Results A swine model was used for these studies (n=12). Ablation lesions with a gap were created in the atrium using fluoroscopy and an electro-anatomical system in the first group (n=5). The animal was then moved to a 3 Tesla MRI system where high-resolution late gadolinium enhancement (LGE) MRI was used to identify the gap. Using a RT-MRI catheter navigation and visualization system the gap area was ablated in the MR scanner. In a second group (n=7) ablation lesions with varying gaps in between were created under RT-MRI guidance and gap lengths determined using LGE MR images were correlated with gap length measured from gross pathology. Gaps up to 1.0 mm were identified using gross pathology and 1.4 mm using LGE MRI. Using a RT-MRI system with active catheter navigation gaps can be targeted acutely, leading to lesion sets with no gaps. The correlation coefficient (R2) between gap length identified using MRI and gross pathology was 0.95. Conclusions Real time MRI system can be used to identify and acutely target gaps in atrial ablation lesion sets. Acute targeting of gaps in ablation lesion sets can potentially lead to significant improvement in clinical outcomes. PMID:23071143

  14. An open source 3-d printed modular micro-drive system for acute neurophysiology.

    PubMed

    Patel, Shaun R; Ghose, Kaushik; Eskandar, Emad N

    2014-01-01

    Current, commercial, electrode micro-drives that allow independent positioning of multiple electrodes are expensive. Custom designed solutions developed by individual laboratories require fabrication by experienced machinists working in well equipped machine shops and are therefore difficult to disseminate into widespread use. Here, we present an easy to assemble modular micro-drive system for acute primate neurophysiology (PriED) that utilizes rapid prototyping (3-d printing) and readily available off the shelf-parts. The use of 3-d printed parts drastically reduces the cost of the device, making it available to labs without the resources of sophisticated machine shops. The direct transfer of designs from electronic files to physical parts also gives researchers opportunities to easily modify and implement custom solutions to specific recording needs. We also demonstrate a novel model of data sharing for the scientific community: a publicly available repository of drive designs. Researchers can download the drive part designs from the repository, print, assemble and then use the drives. Importantly, users can upload their modified designs with annotations making them easily available for others to use. PMID:24736691

  15. Hyperosmolar and methotrexate therapy avoiding surgery in the acute presentation of primary central nervous system lymphoma

    PubMed Central

    Lee, Bryan S.; Juthani, Rupa G.; Healy, Andrew T.; Peereboom, David M.; Recinos, Violette M.

    2014-01-01

    Background: Primary central nervous system lymphoma (PCNSL) is an aggressive type of extra-nodal non-Hodgkin lymphoma. Without treatment, PCNSL is associated with significant morbidity and mortality, including rapid neurological deterioration. In contrast to other high-grade intracranial neoplasms, PCNSL is considered to have a high response rate to conventional medical therapy, especially in younger patients, and therefore warrants particular attention in terms of nonsurgical treatment. Case Description: We report a case of the medical management of acute deterioration due to rapidly growing PCNSL with mass effect to highlight the efficacy of temporization with hyperosmolar therapy while awaiting the known rapid effects of dexamethasone and methotrexate (MTX) treatment. Surgical intervention was avoided, and tumor response was rapid. The patient had corresponding clinical resolution of symptoms of elevated intracranial pressure with return to neurologic baseline. Conclusions: Despite the evidence that PCNSL responds well to steroids and MTX, the rapidity of onset with which this occurs can vary. In patients presenting with mass effect and rapid neurologic decline, there is little evidence to support medical over surgical intervention. Herein we present an illustrative case of a large PCNSL lesion presenting with rapid decline. With clinical improvement in one day and a 50% reduction in tumor volume over less than seven days, the authors present the specific time frame with which PCNSL responds to medical therapy and a safe strategy for medical temporization. PMID:25184099

  16. Acute exposure to 2G phase shifts the rat circadian timing system

    NASA Technical Reports Server (NTRS)

    Hoban-Higgins, T. M.; Murakami, D. M.; Tandon, T.; Fuller, C. A.

    1995-01-01

    The circadian timing system (CTS) provides internal and external temporal coordination of an animal's physiology and behavior. In mammals, the generation and coordination of these circadian rhythms is controlled by a neural pacemaker, the suprachiasmatic nucleus (SCN), located within the hypothalamus. The pacemaker is synchronized to the 24 hour day by time cures (zeitgebers) such as the light/dark cycle. When an animal is exposed to an environment without time cues, the circadian rhythms maintain internal temporal coordination, but exhibit a 'free-running' condition in which the period length is determined by the internal pacemaker. Maintenance of internal and external temporal coordination are critical for normal physiological and psychological function in human and non-human primates. Exposure to altered gravitational environments has been shown to affect the amplitude, mean, and timing of circadian rhythms in species ranging from unicellular organisms to man. However, it has not been determined whether altered gravitational fields have a direct effect on the neural pacemaker, or affect peripheral parameters. In previous studies, the ability of a stimulus to phase shift circadian rhythms was used to determine whether a stimulus has a direct effect on the neural pacemaker. The present experiment was performed in order to determine whether acute exposure to a hyperdynamic field could phase shift circadian rhythms.

  17. Acute lupus pneumonitis followed by intestinal pseudo-obstruction in systemic lupus erythematosus: A case report

    PubMed Central

    JI, CAIHONG; YU, XING; WANG, YONG; SHI, LUFENG

    2016-01-01

    Intestinal pseudo-obstruction (IpsO) and acute lupus pneumonitis (ALP) are uncommon severe complications of systemic lupus erythematosus (SLE). The present study reports the case of a 26-year-old female who presented with abdominal pain, nausea and vomiting as initial symptoms. Computed tomography (CT) scanning revealed the jejunal wall was thickened and streaky, mimicking the presentation of intestinal obstruction. Following emergency surgery, the patient's general condition was aggravated, with evident limb erythematous rashes. A series of laboratory examinations revealed SLE, and combined with patient's medical history IpsO was diagnosed, with a disease Activity Index score of 10. During the therapeutic period, high fever, dyspnea and oxygen saturation (SaO2) reductions were detected, and CT scans indicated lung infiltration, excluding other causes through a comprehensive infectious work-up and a bronchoalveolar lavage examination. ALP was confirmed and treated with high-dose methylprednisolone and gamma globulin supplement. The patient responded well and was discharged in 2 weeks. In the one-year tapering period and after stopping corticosteroids, the patient recovered well with no relapse detected. In conclusion, the manifestation of IpsO in SLE is rare and represents a challenge for the surgeon to establish the correct diagnosis and avoid inappropriate surgical intervention. ALP may be the consequence of emergency surgery, and immediate high-dose glucocorticoid therapy is recommended. PMID:27347044

  18. An Open Source 3-D Printed Modular Micro-Drive System for Acute Neurophysiology

    PubMed Central

    Eskandar, Emad N.

    2014-01-01

    Current, commercial, electrode micro-drives that allow independent positioning of multiple electrodes are expensive. Custom designed solutions developed by individual laboratories require fabrication by experienced machinists working in well equipped machine shops and are therefore difficult to disseminate into widespread use. Here, we present an easy to assemble modular micro-drive system for acute primate neurophysiology (PriED) that utilizes rapid prototyping (3-d printing) and readily available off the shelf-parts. The use of 3-d printed parts drastically reduces the cost of the device, making it available to labs without the resources of sophisticated machine shops. The direct transfer of designs from electronic files to physical parts also gives researchers opportunities to easily modify and implement custom solutions to specific recording needs. We also demonstrate a novel model of data sharing for the scientific community: a publicly available repository of drive designs. Researchers can download the drive part designs from the repository, print, assemble and then use the drives. Importantly, users can upload their modified designs with annotations making them easily available for others to use. PMID:24736691

  19. Divergent mucosal and systemic responses in children in response to acute otitis media.

    PubMed

    Verhoeven, D; Pichichero, M E

    2014-10-01

    Acute otitis media (AOM), induced by respiratory bacteria, is a significant cause of children seeking medical attention worldwide. Some children are highly prone to AOMs, suffering three to four recurrent infections per year (prone). We previously determined that this population of children could have diminished anti-bacterial immune responses in peripheral blood that could fail to limit bacterial colonization in the nasopharynx (NP). Here, we examined local NP and middle ear (ME) responses and compared them to peripheral blood to examine whether the mucosa responses were similar to the peripheral blood responses. Moreover, we examined differences in effector cytokine responses between these two populations in the NP, ME and blood compartments at the onset of an AOM caused by either Streptococcus pneumoniae or non-typeable Haemophilus influenzae. We found that plasma effector cytokines patterned antigen-recall responses of CD4 T cells, with lower responses detected in prone children. ME cytokine levels did not mirror blood, but were more similar to the NP. Interferon (IFN)-γ and interleukin (IL)-17 in the NP were similar in prone and non-prone children, while IL-2 production was higher in prone children. The immune responses diverged in the mucosal and blood compartments at the onset of a bacterial ME infection, thus highlighting differences between local and systemic immune responses that could co-ordinate anti-bacterial immune responses in young children. PMID:24889648

  20. Identification of a New Cyclovirus in Cerebrospinal Fluid of Patients with Acute Central Nervous System Infections

    PubMed Central

    Tan, Le Van; van Doorn, H. Rogier; Nghia, Ho Dang Trung; Chau, Tran Thi Hong; Tu, Le Thi Phuong; de Vries, Michel; Canuti, Marta; Deijs, Martin; Jebbink, Maarten F.; Baker, Stephen; Bryant, Juliet E.; Tham, Nguyen Thi; BKrong, Nguyen Thi Thuy Chinh; Boni, Maciej F.; Loi, Tran Quoc; Phuong, Le Thi; Verhoeven, Joost T. P.; Crusat, Martin; Jeeninga, Rienk E.; Schultsz, Constance; Chau, Nguyen Van Vinh; Hien, Tran Tinh; van der Hoek, Lia; Farrar, Jeremy; de Jong, Menno D.

    2013-01-01

    ABSTRACT Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinal fluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and none of 122 CSFs from patients with noninfectious neurological disorders. Detection rates were similar in patients with CNS infections of unknown etiology and those in whom other pathogens were detected. A similar detection rate in feces from healthy children suggested food-borne or orofecal transmission routes, while high detection rates in feces from pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further research is needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus. PMID:23781068

  1. Role of cardiac output and the autonomic nervous system in the antinatriuretic response to acute constriction of the thoracic superior vena cava.

    NASA Technical Reports Server (NTRS)

    Schrier, R. W.; Humphreys, M. H.; Ufferman, R. C.

    1971-01-01

    Study of the differential characteristics of hepatic congestion and decreased cardiac output in terms of potential afferent stimuli in the antinatriuretic effect of acute thoracic inferior vena cava (TIVC) constriction. An attempt is made to see if the autonomic nervous system is involved in the antinatriuretic effect of acute TIVC or thoracic superior vena cava constriction.

  2. Noninvasive ventilatory correction as an adjunct to an experimental systemic reperfusion therapy in acute ischemic stroke.

    PubMed

    Barlinn, Kristian; Balucani, Clotilde; Palazzo, Paola; Zhao, Limin; Sisson, April; Alexandrov, Andrei V

    2010-01-01

    Background. Obstructive sleep apnea (OSA) is a common condition in patients with acute ischemic stroke and associated with early clinical deterioration and poor functional outcome. However, noninvasive ventilatory correction is hardly considered as a complementary treatment option during the treatment phase of acute ischemic stroke. Summary of Case. A 55-year-old woman with an acute middle cerebral artery (MCA) occlusion received intravenous tissue plasminogen activator (tPA) and enrolled into a thrombolytic research study. During tPA infusion, she became drowsy, developed apnea episodes, desaturated and neurologically deteriorated without recanalization, re-occlusion or intracerebral hemorrhage. Urgent noninvasive ventilatory correction with biphasic positive airway pressure (BiPAP) reversed neurological fluctuation. Her MCA completely recanalized 24 hours later. Conclusions. Noninvasive ventilatory correction should be considered more aggressively as a complementary treatment option in selected acute stroke patients. Early initiation of BiPAP can stabilize cerebral hemodynamics and may unmask the true potential of other therapies. PMID:21052540

  3. Quality of acute stroke care improvement framework for the Paul Coverdell National Acute Stroke Registry: facilitating policy and system change at the hospital level.

    PubMed

    LaBresh, Kenneth A

    2006-12-01

    The Paul Coverdell National Acute Stroke Registry prototypes baseline data collection demonstrated a significant gap in the use of evidenced-based interventions. Barriers to the use of these interventions can be characterized as relating to lack of knowledge, attitudes, and ineffective behaviors and systems. Quality improvement programs can address these issues by providing didactic presentations to disseminate the science and peer interactions to address the lack of belief in the evidence, guidelines, and likelihood of improved patient outcomes. Even with knowledge and intention to provide evidenced-based care, the absence of effective systems is a significant behavioral barrier. A program for quality improvement that includes multidisciplinary teams of clinical and quality improvement professionals has been successfully used to carry out redesign of stroke care delivery systems. Teams are given a methodology to set goals, test ideas for system redesign, and implement those changes that can be successfully adapted to the hospital's environment. Bringing teams from several hospitals together substantially accelerates the process by sharing examples of successful change and by providing strategies to support the behavior change necessary for the adoption of new systems. The participation of many hospitals also creates momentum for the adoption of change by demonstrating observable and successful improvement. Data collection and feedback are useful to demonstrate the need for change and evaluate the impact of system change, but improvement occurs very slowly without a quality improvement program. This quality improvement framework provides hospitals with the capacity and support to redesign systems, and has been shown to improve stroke care considerably, when coupled with an Internet-based decision support registry, and at a much more rapid pace than when hospitals use only the support registry. PMID:17178313

  4. The K(+)-Cl(-) Cotransporter KCC2 and Chloride Homeostasis: Potential Therapeutic Target in Acute Central Nervous System Injury.

    PubMed

    Wu, Haijian; Che, Xiaoru; Tang, Junjia; Ma, Feiqiang; Pan, Kun; Zhao, Mingfei; Shao, Anwen; Wu, Qun; Zhang, Jianmin; Hong, Yuan

    2016-05-01

    The K(+)-Cl(-) cotransporter-2 (KCC2) is a well-known member of the electroneutral cation-chloride cotransporters with a restricted expression pattern to neurons. This transmembrane protein mediates the efflux of Cl(-) out of neurons and exerts a critical role in inhibitory γ-aminobutyric acidergic (GABAergic) and glycinergic neurotransmission. Moreover, KCC2 participates in the regulation of various physiological processes of neurons, including cell migration, dendritic outgrowth, spine morphology, and dendritic synaptogenesis. It is important to note that down-regulation of KCC2 is associated with the pathogenesis of multiple neurological diseases, which is of particular relevance to acute central nervous system (CNS) injury. In this review, we aim to survey the pathogenic significance of KCC2 down-regulation under the condition of acute CNS injuries. We propose that further elucidation of the molecular mechanisms regarding KCC2 down-regulation after acute CNS injuries is necessary because of potential promising avenues for prevention and treatment of acute CNS injury. PMID:25941074

  5. Acute alcohol intoxication and suicide: a gender-stratified analysis of the National Violent Death Reporting System

    PubMed Central

    Kaplan, Mark S; McFarland, Bentson H; Huguet, Nathalie; Conner, Kenneth; Caetano, Raul; Giesbrecht, Norman; Nolte, Kurt B

    2013-01-01

    Objectives Although it is well known that people with alcohol dependence are at a markedly elevated risk for suicide, much less is known about the role of acute alcohol use in suicidal behaviours. The primary aims of this epidemiological study were to assess the prevalence and factors associated with acute alcohol intoxication among 57 813 suicide decedents in 16 states. Methods Data from the restricted National Violent Death Reporting System 2003–2009 for male and female suicide decedents aged 18 years and older were analysed by multiple logistic regression to compare decedents with and without acute alcohol intoxication (defined as blood alcohol concentration (BAC) ≥0.08 g/dl). Results Among men, those who were younger, American Indian/Alaska Native, Hispanic, veterans, of lower educational attainment, deceased from a self-inflicted firearm injury or hanging/suffocation and residing in rural areas were more likely to have been intoxicated at the time of death. Among women, the factors associated with a BAC ≥0.08 g/dl were younger age, being American Indian/Alaska Native, and using a firearm, hanging/suffocation or falling as method of death. Conclusions In both men and women, alcohol intoxication was associated with violent methods of suicide and declined markedly with age, suggesting that addressing risks associated with acute alcohol use may be of the greatest aid in the prevention of violent suicides among young and middle age adults. PMID:22627777

  6. Sumatriptan iontophoretic transdermal system: a review of its use in patients with acute migraine.

    PubMed

    Garnock-Jones, Karly P

    2013-09-01

    The sumatriptan iontophoretic transdermal system (ZECUITY®) [hereafter referred to as sumatriptan TDS] is the first transdermal treatment for migraine to be approved by the US FDA. This article reviews the available pharmacologic properties of sumatriptan TDS and its clinical efficacy and tolerability for the acute treatment of adult patients with migraine with or without aura. Sumatriptan, a selective 5-hydroxy-tryptamine receptor subtype 1 (5-HT₁) agonist, is presumed to exert its therapeutic effect on migraine patients by binding to the 5-HT(1B/1D) receptors on intracranial blood vessels and sensory nerves of the trigeminal system, resulting in cranial vessel constriction and the inhibition of the release of pro-inflammatory neuropeptides and plasma extravasation. In a well designed, phase III clinical trial, sumatriptan TDS was shown to be more effective than placebo at treating a single migraine attack, with significantly more sumatriptan TDS than placebo recipients being headache pain free and nausea free at 2 hours. These data were supported by a long-term, repeat-use study over 12 months. Additionally, sumatriptan TDS was generally well tolerated in clinical trials; the most common adverse events were application-site reactions. The sumatriptan TDS formulation avoids the gastrointestinal tract, and has a controlled, sustained delivery, allowing for patients with migraine-associated nausea and vomiting to receive treatment without the risk of inconsistent absorption or avoidance of tablet use (associated with oral delivery of the drug in these patients). Moreover, it may offer a useful alternative to the nasal spray or subcutaneous sumatriptan formulations. However, definitive conclusions on the comparative efficacy and tolerability of sumatriptan TDS versus other sumatriptan formulations or other migraine drugs are not as yet possible, and data from comparative trials would be of great interest. Sumatriptan TDS is a useful addition to the treatment

  7. Acute Disseminated Encephalomyelitis Onset: Evaluation Based on Vaccine Adverse Events Reporting Systems

    PubMed Central

    Perrone, Valentina; Pozzi, Marco; Antoniazzi, Stefania; Clementi, Emilio; Radice, Sonia

    2013-01-01

    Objective To evaluate epidemiological features of post vaccine acute disseminated encephalomyelitis (ADEM) by considering data from different pharmacovigilance surveillance systems. Methods The Vaccine Adverse Event Reporting System (VAERS) database and the EudraVigilance post-authorisation module (EVPM) were searched to identify post vaccine ADEM cases. Epidemiological features including sex and related vaccines were analysed. Results We retrieved 205 and 236 ADEM cases from the EVPM and VAERS databases, respectively, of which 404 were considered for epidemiological analysis following verification and causality assessment. Half of the patients had less than 18 years and with a slight male predominance. The time interval from vaccination to ADEM onset was 2-30 days in 61% of the cases. Vaccine against seasonal flu and human papilloma virus vaccine were those most frequently associated with ADEM, accounting for almost 30% of the total cases. Mean number of reports per year between 2005 and 2012 in VAERS database was 40±21.7, decreasing after 2010 mainly because of a reduction of reports associated with human papilloma virus and Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B vaccines. Conclusions This study has a high epidemiological power as it is based on information on adverse events having occurred in over one billion people. It suffers from lack of rigorous case verification due to the weakness intrinsic to the surveillance databases used. At variance with previous reports on a prevalence of ADEM in childhood we demonstrate that it may occur at any age when post vaccination. This study also shows that the diminishing trend in post vaccine ADEM reporting related to Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B and human papilloma virus vaccine groups is most likely due to a decline in vaccine coverage indicative of a reduced attention to this adverse drug reaction. PMID:24147076

  8. Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful programs.

    PubMed

    Straub, Rainer H; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3-8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting-cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs. PMID:26817483

  9. Challenges and Rewards on the Road to Translational Systems Biology in Acute Illness: Four Case Reports from Interdisciplinary Teams

    PubMed Central

    An, Gary; Hunt, C. Anthony; Clermont, Gilles; Neugebauer, Edmund; Vodovotz, Yoram

    2007-01-01

    Introduction Translational systems biology approaches can be distinguished from mainstream systems biology in that their goal is to drive novel therapies and streamline clinical trials in critical illness. One systems biology approach, dynamic mathematical modeling (DMM), is increasingly used in dealing with the complexity of the inflammatory response and organ dysfunction. The use of DMM often requires a broadening of research methods and a multidisciplinary team approach that includes bioscientists, mathematicians, engineers, and computer scientists. However, the development of these groups must overcome domain-specific barriers to communication and understanding. Methods We present four case studies of successful translational, interdisciplinary systems biology efforts, which differ by organizational level from an individual to an entire research community. Results Case 1 is a single investigator involved in DMM of the acute inflammatory response at Cook County Hospital, in which extensive translational progress was made using agent-based models of inflammation and organ damage. Case 2 is a community-level effort from the University of Witten-Herdecke in Cologne, whose efforts have led to the formation of the Society for Complexity in Acute Illness. Case 3 is an institution-based group, the Biosystems Group at the University of California, San Francisco, whose work has included a focus on a common lexicon for DMM. Case 4 is an institution-based, trans-disciplinary research group (the Center for Inflammation and Regenerative Modeling at the University of Pittsburgh, whose modeling work has led to internal education efforts, grant support, and commercialization. Conclusion A transdisciplinary approach, which involves team interaction in an iterative fashion to address ambiguity and is supported by educational initiatives, is likely to be necessary for DMM in acute illness. Community-wide organizations such as the Society of Complexity in Acute Illness (SCAI) must

  10. Effect of adopting a new histological grading system of acute rejection after heart transplantation

    PubMed Central

    Balk, A.; Zondervan, P.; van der Meer, P.; van Gelder, T.; Mochtar, B.; Simoons, M.; Weimar, W.

    1997-01-01

    Background—Treatment policy of acute rejection after heart transplantation has been changed after adopting the ISHLT endomyocardial biopsy grading system in 1991.
Objective—To determine the effect of this policy change on clinical outcome after transplantation.
Methods—The outcome of 147 patients who had a transplant before (early group, median follow up 96 months) and 114 patients who had a transplant after (late group, median follow up 41 months) the introduction of the ISHLT biopsy grading system was studied retrospectively. Initially "moderate rejection" according to Billingham's conventional criteria was treated. From January 1991 grade 3A and higher was considered to require intensification of immunosuppression.
Results—There were some differences between the two groups: recipients (50 v 44 years) as well as donors (28 v 24 years) were older in the "late group" and more patients of this group received early anti-T cell prophylaxis (92% v 56%). Despite more extensive use of early prophylaxis more rejection episodes were diagnosed (2.4 v 1.4) and considerably more courses of rejection treatment were instituted in the late compared with the early group (3.2 v 1.5). There were no deaths because of rejection in the late group, however, more infections occurred within the first year (mean 1.8 v 1.4) and more non-skin malignancies within the first 41 months were diagnosed (8 of 57 v 6 of 147, 95% CIs of difference includes 0). The incidence of graft vascular disease in the late group has been comparable to the early group until now. 
Conclusion—The interpretation of the ISHLT grading system resulted in lowering of the threshold for the diagnosis of rejection thereby increasing the number of rejections and subsequently the immunosuppressive load and its complications.

 Keywords: transplantation;  biopsy grading system;  rejection PMID:9470880

  11. Factors Predicting the Effects of Hybrid Assistive Limb Robot Suit during the Acute Phase of Central Nervous System Injury

    PubMed Central

    CHIHARA, Hideo; TAKAGI, Yasushi; NISHINO, Kazunari; YOSHIDA, Kazumichi; ARAKAWA, Yoshiki; KIKUCHI, Takayuki; TAKENOBU, Yohei; MIYAMOTO, Susumu

    2016-01-01

    To improve the activities of daily living of patients with injury to the central nervous system, physical therapy starting from the acute phase of the injury is important. Recently, the efficacy of physical therapy using a hybrid assistive limb (HAL) robot suit was reported. However, individual differences exist in the effects of HAL. We investigated factors predicting the effects of HAL in 15 patients at our institution with central nervous system injury, primarily due to stroke, who underwent training using HAL during the acute phase. Patients were classified as either “with HAL suitability” or “without HAL suitability” based on scores from 10-m walking speed, gait, satisfaction, and pain. In both groups, Brunnstrom stage before HAL intervention, Fugl-Meyer assessment (FMA), stroke impairment assessment set (SIAS), and functional independence measure (FIM) were evaluated. Although motor function items did not differ significantly, FIM cognitive function items (P = 0.036), visuospatial perception items on SIAS (P = 0.0277), and pain items on SIAS (P = 0.0122) differed significantly between groups. These results indicated that training using HAL does not involve pain in patients with central nervous system injury during the acute phase, and exhibits positive effects in patients without pain and with high communication ability and visuospatial perception function. When conducting HAL intervention, incorporating functional assessment scores (FIM and SIAS), including peripheral items, may be useful to predict the suitability of HAL. PMID:26538291

  12. Survival in acute and severe low o environment: use of a genetic model system.

    PubMed

    Azad, Priti; Haddad, Gabriel G

    2009-10-01

    Hypoxia whether present during physiologic states (e.g., embryogenesis) or during pathologic states (e.g., obstructive sleep apnea and sickle cell anemia), challenges the vertebrate or invertebrate organism. Clearly, hypoxia can lead to sublethal cell injury or death and consequently organ or systemic injury and failure, depending on severity. We discovered that the adult Drosophila melanogaster is tolerant to a low O(2) environment, withstanding approximately 3-4 hours of total O(2) deprivation or anoxia without showing any evidence of cell injury. This opened major avenues for us since the Drosophila has been used so effectively in so many relevant research areas. We investigated the changes in gene expression in D. melanogaster after severe (1% O(2)) intermittent or constant hypoxia treatment for 2.5 hours. Our microarray analysis has identified multiple gene families that are up- or downregulated in response to acute constant (CH) and intermittent hypoxia (IH). We observed that even for short-term the gene expression response to IH and CH varied not only in the number of genes but also type of gene families. Furthermore, by utilizing powerful Drosophila genetic tools we studied the role of single genes (up- or downregulated in arrays) in survival under either paradigm in adult flies. We observed significant increased adult survival (as compared to controls) of P-element lines for Hsp70 and Hsp23 genes during CH and Mdr49 and l (2)08717 genes during IH. This suggests that the increased transcript levels as observed in array data after either paradigm play an important role under severe hypoxia. Indeed, we found for example that over-expressing Hsp70 in vivo in specific fly organs (such as heart) significantly increased adult survival during CH as compared to controls. These data provide further clues about the mechanisms by which intermittent and constant hypoxia lead to cell injury and morbidity or adaptation and survival. PMID:19845605

  13. Simvastatin is associated with reduced risk of acute pancreatitis: findings from a regional integrated healthcare system

    PubMed Central

    Wu, Bechien U; Pandol, Stephen J; Liu, In-Lu Amy

    2016-01-01

    Objective To characterise the relationship between simvastatin and risk of acute pancreatitis (AP). Design We conducted a retrospective cohort study (2006–2012) on data from an integrated healthcare system in southern California. Exposure to simvastatin was calculated from time of initial dispensation until 60 days following prescription termination. AP cases were defined by ICD-9 CM 577.0 and serum lipase≥3 times normal. Patients were censored at death, last follow-up, and onset of AP or end-of-study. Incidence rate of pancreatitis among simvastatin users was compared with the adult reference population. Robust Poisson regression was used to generate risk ratio (RR) estimates for simvastatin use adjusted for age, gender, race/ethnicity, gallstone-related disorders, hypertriglyceridaemia, smoking and alcohol dependence. Analysis was repeated for atorvastatin. Results Among 3 967 859 adult patients (median duration of follow-up of 3.4 years), 6399 developed an initial episode of AP. A total of 707 236 patients received simvastatin during the study period. Patients that received simvastatin were more likely to have gallstone-related disorders, alcohol dependence or hypertriglyceridaemia compared with the reference population. Nevertheless, risk of AP was significantly reduced with simvastatin use, crude incidence rate ratio 0.626 (95% CL 0.588, 0.668), p<0.0001. In multivariate analysis, simvastatin was independently associated with reduced risk of pancreatitis, adjusted RR 0.29 (95% CL 0.27, 0.31) after adjusting for age, gender, race/ethnicity, gallstone disorders, alcohol dependence, smoking and hypertriglyceridaemia. Similar results were noted with atorvastatin, adjusted RR 0.33 (0.29, 0.38). Conclusions Use of simvastatin was independently associated with reduced risk of AP in this integrated healthcare setting. Similar findings for atorvastatin suggest a possible class effect. PMID:24742713

  14. Decongestion Strategies and Renin-Angiotensin-Aldosterone System Activation in Acute Heart Failure

    PubMed Central

    Mentz, Robert J.; Stevens, Susanna R.; DeVore, Adam D.; Lala, Anuradha; Vader, Justin M.; AbouEzzeddine, Omar F.; Khazanie, Prateeti; Redfield, Margaret M.; Stevenson, Lynne W.; O'Connor, Christopher M.; Goldsmith, Steven R.; Bart, Bradley A.; Anstrom, Kevin J.; Hernandez, Adrian F.; Braunwald, Eugene; Felker, G. Michael

    2014-01-01

    Background High dose diuretics in patients with acute heart failure (AHF) are thought to activate the renin-angiotensin-aldosterone system (RAAS), and alternative decongestion strategies, such as ultrafiltration (UF), have been proposed to mitigate this RAAS activation. Methods We analyzed 427 AHF patients enrolled in the DOSE-AHF and CARRESS-HF trials. We assessed the relationship between two markers of RAAS activation (plasma renin activity [PRA] and aldosterone) from baseline to 72-96h and decongestion strategy; high vs. low-dose and continuous infusion vs. bolus furosemide for DOSE-AHF and UF vs. stepped pharmacologic care for CARRESS-HF. We determined the relationship between RAAS biomarkers and 60-day outcomes. Results Patients with greater RAAS activation at baseline had lower blood pressures, lower serum sodium, and higher BUN. Continuous infusion furosemide and UF were associated with greater PRA increases (median +1.66 vs. +0.66 ng/mL/h with continuous vs. bolus, P=0.021; +4.05 vs. +0.56 ng/mL/h with UF vs. stepped care, P=0.014). There was no significant difference in RAAS biomarker change with high vs. low-dose diuretics (both P>0.5). Neither baseline log PRA nor log aldosterone was associated with increased death/HF hospitalization (HR for a doubling 1.05; 95% CI: 0.98-1.13, P=0.18 and HR 1.13; 95% CI: 0.99-1.28, P=0.069, respectively). The change in RAAS biomarkers from baseline to 72-96 h was not associated with outcomes (both P>0.5). Conclusions High-dose loop diuretics did not result in greater RAAS activation than low-dose diuretics. UF resulted in greater PRA increase than stepped pharmacologic care. Neither PRA nor aldosterone was significantly associated with short-term outcomes in this cohort. PMID:25543972

  15. Central nervous system effects of meclizine and dimenhydrinate: evidence of acute tolerance to antihistamines.

    PubMed

    Manning, C; Scandale, L; Manning, E J; Gengo, F M

    1992-11-01

    Relative daytime drowsiness and performance impairment produced by meclizine and dimenhydrinate was assessed in 24 healthy male volunteers. Subjects received either dimenhydrinate, 100 mg, at 8:00 AM, 12:00 PM, and 4:00 PM; meclizine, 50 mg, at 8:00 AM, with placebo at 12:00 PM and 4:00 PM; or placebo at all three times in this randomized, double-blind, three-way crossover study. Impairment of mental performance was assessed by choice reaction time testing and digit symbol substitution scores. Drowsiness was self-assessed on the Stanford Sleepiness Scale and on a visual analog scale. Both antihistamines produced changes in digit symbol substitution, recognition time, and subjective assessments of sleepiness different from placebo. Expressed as change from baseline, the greatest reductions in digit symbol substitution scores after dimenhydrinate occurred 3 hours after the first dose (6.6 +/- 7) and were not different from the greatest measured change after meclizine (5.8 +/- 8), which occurred 9 hours after the dose was administered. Similar results were obtained with the other psychometric test scores. Self-rated sleepiness after dimenhydrinate was greatest 1 hour after the first dose, and was significantly greater than the largest degree of sleepiness after meclizine, which occurred at 7 hours after the dose. The effects of the first dose of dimenhydrinate on psychometric test scores were compared with the magnitude of the effects produced by subsequent doses. The magnitude of effect of the first dose of dimenhydrinate was significantly greater than the magnitude of effect produced by subsequent doses. The data suggest the possibility that acute tolerance to central nervous system impairment develops with multiple doses of dimenhydrinate. PMID:1474173

  16. EphB1 Suppression in Acute Myelogenous Leukemia: Regulating the DNA Damage Control System

    PubMed Central

    Kampen, K.R.; Scherpen, F.J.G.; Garcia-Manero, G.; Yang, H.; Kaspers, G.J.L.; Cloos, J.; Zwaan, C.M.; van den Heuvel-Eibrink, M.M.; Kornblau, S.M.; De Bont, E.S.J.M.

    2016-01-01

    Loss of ephrin receptor (EphB1) expression may associate with aggressive cancer phenotypes; however, the mechanism of action remains unclear. To gain detailed insight into EphB1 function in acute myelogenous leukemia (AML), comprehensive analysis of EphB1 transcriptional regulation was conducted. In AML cells, EphB1 transcript was inversely correlated with EphB1 promoter methylation. The presence of EphB1 allowed EfnB1 ligand–mediated p53 DNA binding, leading to restoration of the DNA damage response (DDR) cascade by the activation of ATR, Chk1, p53, p21, p38, CDK1tyr15, and Bax, and downregulation of HSP27 and Bcl2. Comparatively, reintroduction of EphB1 expression in EphB1-methylated AML cells enhanced the same cascade of ATR, Chk1, p21, and CDK1tyr15, which consequently enforced programmed cell death. Interestingly, in pediatric AML samples, EphB1 peptide phosphorylation and mRNA expression were actively suppressed as compared with normal bone marrow, and a significant percentage of the primary AML specimens had EphB1 promoter hyper-methylation. Finally, EphB1 repression associated with a poor overall survival in pediatric AML. Combined, the contribution of EphB1 to the DDR system reveals a tumor-suppressor function for EphB1 in pediatric AML. Implications The tumor-suppressor function of EphB1 is clinically relevant across many malignancies, suggesting that EphB1 is an important regulator of common cancer cell trans forming pathways. PMID:25944917

  17. Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems

    PubMed Central

    Dainiak, Nicholas; Gent, Robert Nicolas; Carr, Zhanat; Schneider, Rita; Bader, Judith; Buglova, Elena; Chao, Nelson; Coleman, C. Norman; Ganser, Arnold; Gorin, Claude; Hauer-Jensen, Martin; Huff, L. Andrew; Lillis-Hearne, Patricia; Maekawa, Kazuhiko; Nemhauser, Jeffrey; Powles, Ray; Schünemann, Holger; Shapiro, Alla; Stenke, Leif; Valverde, Nelson; Weinstock, David; White, Douglas; Albanese, Joseph; Meineke, Viktor

    2013-01-01

    Objectives The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature. Methods English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made. Results No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/ orshock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak

  18. Acute Bronchitis

    MedlinePlus

    ... or though physical contact (for example, on unwashed hands). Being exposed to tobacco smoke, air pollution, dusts, vapors, and fumes can also cause acute bronchitis. Less often, bacteria can also cause acute bronchitis. To diagnose acute ...

  19. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... control. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  20. Acute urticaria as a side effect of the Mirena® (levonorgestrel-releasing intrauterine system): a case report

    PubMed Central

    2014-01-01

    Background The levonorgestrel intrauterine system, Mirena®, is widely used for contraception and the treatment of idiopathic menorrhagia. Here, we reported one case of acute urticaria following Mirena® implantation to increase the awareness of possible adverse side effects associated with Mirena®. Case presentation The case presented is a 27-year-old Chinese woman who received Mirena® implantation for her adenomyosis and menorrhagia. The operation was successful and the patient did not experience any discomfort during the operation. However, she developed acute urticaria on her entire body accompanied with pruritic, slight left lower quadrant pain, and slight dizziness two hours after the operation. The patient was recommended to have the Mirena® removed immediately, and she took 10 mg oral methylprednisolone and 5 mg desloratadine tablet daily for five days. Her urticaria resolved and did not recur. Conclusion The patient’s acute urticaria seems to have been associated with the Mirena® levonorgestrel intrauterine system implantation, since she had no history of allergic reactions to materials used during the operation such as plastic, metal, alcohol, medications, and povidone-iodine. PMID:24708811

  1. Amelioration of Acute Kidney Injury in Lipopolysaccharide-Induced Systemic Inflammatory Response Syndrome by an Aldose Reductase Inhibitor, Fidarestat

    PubMed Central

    Takahashi, Kazunori; Mizukami, Hiroki; Kamata, Kosuke; Inaba, Wataru; Kato, Noriaki; Hibi, Chihiro; Yagihashi, Soroku

    2012-01-01

    Background Systemic inflammatory response syndrome is a fatal disease because of multiple organ failure. Acute kidney injury is a serious complication of systemic inflammatory response syndrome and its genesis is still unclear posing a difficulty for an effective treatment. Aldose reductase (AR) inhibitor is recently found to suppress lipopolysaccharide (LPS)-induced cardiac failure and its lethality. We studied the effects of AR inhibitor on LPS-induced acute kidney injury and its mechanism. Methods Mice were injected with LPS and the effects of AR inhibitor (Fidarestat 32 mg/kg) before or after LPS injection were examined for the mortality, severity of renal failure and kidney pathology. Serum concentrations of cytokines (interleukin-1β, interleukin-6, monocyte chemotactic protein-1 and tumor necrosis factor-α) and their mRNA expressions in the lung, liver, spleen and kidney were measured. We also evaluated polyol metabolites in the kidney. Results Mortality rate within 72 hours was significantly less in LPS-injected mice treated with AR inhibitor both before (29%) and after LPS injection (40%) than untreated mice (90%). LPS-injected mice showed marked increases in blood urea nitrogen, creatinine and cytokines, and AR inhibitor treatment suppressed the changes. LPS-induced acute kidney injury was associated with vacuolar degeneration and apoptosis of renal tubular cells as well as infiltration of neutrophils and macrophages. With improvement of such pathological findings, AR inhibitor treatment suppressed the elevation of cytokine mRNA levels in multiple organs and renal sorbitol accumulation. Conclusion AR inhibitor treatment ameliorated LPS-induced acute kidney injury, resulting in the lowered mortality. PMID:22253906

  2. Neurofunctional endpoints assessed in human neuroblastoma SH-SY5Y cells for estimation of acute systemic toxicity

    SciTech Connect

    Gustafsson, Helena; Runesson, Johan; Lundqvist, Jessica; Lindegren, Helene; Axelsson, Viktoria; Forsby, Anna

    2010-06-01

    The objective of the EU-funded integrated project ACuteTox is to develop a strategy in which general cytotoxicity, together with organ-specific toxicity and biokinetic features, are used for the estimation of human acute systemic toxicity. Our role in the project is to characterise the effect of reference chemicals with regard to neurotoxicity. We studied cell membrane potential (CMP), noradrenalin (NA) uptake, acetylcholine esterase (AChE) activity, acetylcholine receptor (AChR) signalling and voltage-operated calcium channel (VOCC) function in human neuroblastoma SH-SY5Y cells after exposure to 23 pharmaceuticals, pesticides or industrial chemicals. Neurotoxic alert chemicals were identified by comparing the obtained data with cytotoxicity data from the neutral red uptake assay in 3T3 mouse fibroblasts. Furthermore, neurotoxic concentrations were correlated with estimated human lethal blood concentrations (LC50). The CMP assay was the most sensitive assay, identifying eight chemicals as neurotoxic alerts and improving the LC50 correlation for nicotine, lindane, atropine and methadone. The NA uptake assay identified five neurotoxic alert chemicals and improved the LC50 correlation for atropine, diazepam, verapamil and methadone. The AChE, AChR and VOCC assays showed limited potential for detection of acute toxicity. The CMP assay was further evaluated by testing 36 additional reference chemicals. Five neurotoxic alert chemicals were generated and orphendrine and amitriptyline showed improved LC50 correlation. Due to the high sensitivity and the simplicity of the test protocol, the CMP assay constitutes a good candidate assay to be included in an in vitro test strategy for prediction of acute systemic toxicity.

  3. Acute systemic accumulation of acrolein in mice by inhalation at a concentration similar to that in cigarette smoke

    PubMed Central

    Tully, Melissa; Zheng, Lingxing; Acosta, Glen; Tian, Ran; Shi, Riyi

    2015-01-01

    Cigarette smoke is an important environmental factor associated with a wide array of public health concerns. Acrolein, a component of tobacco smoke and a known toxin to various cell types, may be a key pathological factor mediating the adverse effects linked with tobacco smoke. Although acrolein is known to accumulate in the respiratory system after acute nasal exposure, it is not clear if it accumulates systemically, and less is known in the nervous system. The aim of this study was to assess the degree of acrolein accumulation in the circulation and in the spinal cord following acute acrolein inhalation in mice. Using a laboratory-fabricated inhalation chamber, we found elevated urinary 3-HPMA, an acrolein metabolite, and increased acrolein adducts in the spinal cord after weeks of nasal exposure to acrolein at a concentration similar to that in tobacco smoke. The data indicated that acrolein is absorbed into the circulatory system and some enters the nervous system. It is expected that these findings may facilitate further studies to probe the pathological role of acrolein in the nervous system resulting from smoke and other external sources. PMID:25446876

  4. Systemic thrombolysis with recombinant tissue plasminogen activator for acute life-threatening Blalock-Taussig shunt obstruction

    PubMed Central

    Diaz, Franco; Sasser, William C.; Law, Mark A.; Alten, Jeffrey A.

    2016-01-01

    Modified Blalock-Taussig shunt (mBTS) obstruction can be life-threatening, especially when it represents the only source of pulmonary blood flow. Current therapeutic options to reverse obstruction include surgical shunt revision/replacement, interventional endovascular procedures including balloon angioplasty and/or stent placement, and a combination of local and systemic thrombolytic therapy. We report two cases of acute mBTS thrombosis successfully treated with systemic recombinant tissue plasminogen activator in infants convalescing after cardiac surgery when the clinical status and resources precluded traditionally described rescue therapies. PMID:27555699

  5. Systemic thrombolysis with recombinant tissue plasminogen activator for acute life-threatening Blalock-Taussig shunt obstruction.

    PubMed

    Diaz, Franco; Sasser, William C; Law, Mark A; Alten, Jeffrey A

    2016-07-01

    Modified Blalock-Taussig shunt (mBTS) obstruction can be life-threatening, especially when it represents the only source of pulmonary blood flow. Current therapeutic options to reverse obstruction include surgical shunt revision/replacement, interventional endovascular procedures including balloon angioplasty and/or stent placement, and a combination of local and systemic thrombolytic therapy. We report two cases of acute mBTS thrombosis successfully treated with systemic recombinant tissue plasminogen activator in infants convalescing after cardiac surgery when the clinical status and resources precluded traditionally described rescue therapies. PMID:27555699

  6. THE ACUTE PHASE RESPONSE IN E. COLI CHALLENGED PIGS TREATED WITH SYSTEMIC ANTIBIOTICS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Changes in serum C-reactive protein (CRP), haptoglobin (HG) and cortisol (CS), and rectal temperature (RT) were evaluated in response to an acute enterotoxemia elicited by antibiotic injection. Twenty-four, 24-day old, pigs were individually housed and provided feed and water ad libitum. Twelve pig...

  7. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats#

    EPA Science Inventory

    Acute ozone exposure increases circulating stress hormones and induces metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for both ozone-induced metabolic effects and lung injury. Male Wistar-Kyoto rats ...

  8. Effects of Local Pancreatic Renin-Angiotensin System on the Microcirculation of Rat with Severe Acute Pancreatitis.

    PubMed

    Pan, Zhijian; Feng, Ling; Long, Haocheng; Wang, Hui; Feng, Jiarui; Chen, Feixiang

    2015-07-01

    Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis. PMID:26170733

  9. Left ventricular apical thrombus after systemic thrombolysis with recombinant tissue plasminogen activator in a patient with acute ischemic stroke

    PubMed Central

    Doepp, Florian; Sanad, Wasiem; Schreiber, Stephan J; Baumann, Gert; Borges, Adrian C

    2005-01-01

    Background Thrombolysis with recombinant tissue plasminogen activator (rtPA) is an established treatment in acute stroke. To prevent rethrombosis after rtPA therapy, secondary anticoagulation with heparin is commonly performed. However, the recommended time-point and extent of heparin treatment vary and are not well investigated. Case presentation We report a 61-year-old man who developed an acute global aphasia and right-sided hemiparesis. Cranial CT was normal and systemic thrombolytic therapy with tPA was started 120 minutes after symptom onset. Low-dose subcutaneous heparin treatment was initiated 24 hours later. Transthoracic echocardiography (TTE) 12 hours after admission showed slightly reduced left ventricular ejection fraction (LVEF) but was otherwise normal. 48 hours later the patient suddenly deteriorated with clinical signs of dyspnea and tachycardia. TTE revelead a large left ventricular apical thrombus as well as a reduction of LVEF to 20 %. Serial further TTE investigations demonstrated a complete resolution of the thrombus and normalisation of LVEF within two days. Conclusion Our case demonstrates an intracardiac thrombus formation following rtPA treatment of acute stroke, probably caused by secondary hypercoagulability. Rethrombosis or new thrombus formation might be an underestimated complication of rtPA therapy and potentially explain cases of secondary stroke progression. PMID:15918893

  10. Facilitators and barriers to doing workplace mental health research: Case study of acute psychological trauma in a public transit system.

    PubMed

    Links, Paul S; Bender, Ash; Eynan, Rahel; O'Grady, John; Shah, Ravi

    2016-03-10

    The Acute Psychological Trauma (APT) Study was a collaboration between an acute care hospital, a specialized multidisciplinary program designed to meet the mental health needs of injured workers, and a large urban public transit system. The overall purpose was to evaluate a Best Practices Intervention (BPI) for employees affected by acute psychological trauma compared to a Treatment as Usual (TAU) group. The specific purpose is to discuss facilitators and barriers that were recognized in implementing and carrying out mental health research in a workplace setting. Over the course of the APT study, a joint implementation committee was responsible for day-to-day study operations and made regular observations on the facilitators and barriers that arose throughout the study. The facilitators to this study included the longstanding relationships among the partners, increased recognition for the need of mental health research in the workplace, and the existence of a community advisory committee. The significant barriers to doing this study of mental health research in the workplace included differences in organizational culture, inconsistent union support, co-interventions, and stigma. Researchers and funding agencies need to be flexible and provide additional resources in order to overcome the barriers that can exist doing workplace mental health research. PMID:26967029

  11. Effects of Local Pancreatic Renin-Angiotensin System on the Microcirculation of Rat with Severe Acute Pancreatitis

    PubMed Central

    Feng, Ling; Long, Haocheng; Wang, Hui; Feng, Jiarui; Chen, Feixiang

    2015-01-01

    Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis. PMID:26170733

  12. Public Health Response Systems In-Action: Learning from Local Health Departments’ Experiences with Acute and Emergency Incidents

    PubMed Central

    Hunter, Jennifer C.; Yang, Jane E.; Crawley, Adam W.; Biesiadecki, Laura; Aragón, Tomás J.

    2013-01-01

    As part of their core mission, public health agencies attend to a wide range of disease and health threats, including those that require routine, acute, and emergency responses. While each incident is unique, the number and type of response activities are finite; therefore, through comparative analysis, we can learn about commonalities in the response patterns that could improve predictions and expectations regarding the resources and capabilities required to respond to future acute events. In this study, we interviewed representatives from more than 120 local health departments regarding their recent experiences with real-world acute public health incidents, such as infectious disease outbreaks, severe weather events, chemical spills, and bioterrorism threats. We collected highly structured data on key aspects of the incident and the public health response, particularly focusing on the public health activities initiated and community partners engaged in the response efforts. As a result, we are able to make comparisons across event types, create response profiles, and identify functional and structural response patterns that have import for future public health preparedness and response. Our study contributes to clarifying the complexity of public health response systems and our analysis reveals the ways in which these systems are adaptive to the character of the threat, resulting in differential activation of functions and partners based on the type of incident. Continued and rigorous examination of the experiences of health departments throughout the nation will refine our very understanding of what the public health response system is, will enable the identification of organizational and event inputs to performance, and will allow for the construction of rich, relevant, and practical models of response operations that can be employed to strengthen public health systems. PMID:24236137

  13. Early multi-system organ failure associated with acute pancreatitis: a plea for a conservative therapeutic strategy.

    PubMed

    Dugernier, T; Reynaert, M; Laterre, P F

    2003-01-01

    The mortality of severe acute pancreatitis still ranges between 10 and 20%. Nowadays, infected pancreatic necrosis is the leading cause of death. Despite advances in intensive care therapy, however, early and worsening multi-system organ failure remains a source of substantial morbidity and still accounts for 20 to 50% of the deaths. In recent years, the systemic inflammatory response syndrome and the relevant cascades of inflammatory mediators have been implicated as the key factor in the emergence of remote tissue damage. Early multi-system organ failure that supervenes in the first week is typically associated with a sterile necrotizing process. There are no pathophysiological, clinical or economical data to support the practice of debridement of sterile necrosis to prevent or to control early multi-system organ failure. This issue has never been addressed in a controlled study. Besides intensive care support, non-surgical therapeutic modalities including urgent endoscopic sphincterotomy for impacted stones, antibiotic prophylaxis for the prevention of pancreatic infection and early jejunal nutrition have been specifically developed hopefully to attenuate multiple organ failure, to obviate the need of surgical drainage and to improve survival. Fine needle aspiration of necrotic areas must be incorporated in any conservative therapeutic strategy in order to identify and not to jeopardize those with infected necrosis that remains an absolute indication for drainage. A specific treatment of acute pancreatitis is still lacking, so far. However, there is ample experimental and pathophysiological evidence in favour of immunomodulatory therapy in severe acute pancreatitis. The administration of one or several antagonists of inflammatory mediators possibly combined with a protease inhibitor may at last provide the opportunity to interfere with the two major determinants of prognosis: the severity of multiple organ failure and the extent of necrotic areas that creates

  14. Acute ST elevation myocardial infarction in fulminant systemic p-ANCA vasculitis: a rare catastrophic complication.

    PubMed

    Mathur, Kanupriya; Saini, Aditya; Bah, Tonjeh; Katikaneni, Pavan

    2016-01-01

    A 45-year-old Caucasian man presented to the hospital with a 3-month history of fatigue, bilateral upper and lower limb paresthesias and gradually worsening ascending paralysis. A few weeks later, he developed acute renal failure requiring haemodialysis. Investigations revealed presence of myeloperoxidase (MPO) perinuclear antineutrophil cytoplasmic antibodies (ANCA). Renal biopsy was conclusive for rapidly progressive glomerulonephritis with crescents. Treatment for ANCA positive vasculitis was initiated with pulsed steroids, cyclophosphamide and plasmapheresis. The hospital course took an unexpected turn when the patient developed acute chest pain with an EKG consistent with inferior ST elevation myocardial infarction (STEMI). Urgent left heart catheterisation revealed distal occlusions in multivessel coronary distribution. Coronary involvement is rare in ANCA vasculitis and STEMI has not been reported in MPO-ANCA positive vasculitis, to the best of our knowledge. PMID:27358099

  15. Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice

    PubMed Central

    Doeppner, T R; Kaltwasser, B; Teli, M K; Bretschneider, E; Bähr, M; Hermann, D M

    2014-01-01

    Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests. Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared with transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood–brain barrier (BBB), reduction in microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity. Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment. PMID:25144721

  16. Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice.

    PubMed

    Doeppner, T R; Kaltwasser, B; Teli, M K; Bretschneider, E; Bähr, M; Hermann, D M

    2014-01-01

    Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests. Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared with transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood-brain barrier (BBB), reduction in microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity. Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment. PMID:25144721

  17. PULMONARY AND SYSTEMIC HEALTH EFFECTS OF ACUTE AND SUBCHRONIC EXPOSURE TO SMOKE OBSCURANT SGF-2

    EPA Science Inventory

    Sixty-day old, male rats were exposed to air, 0.5 or 1.5 ml/1 fog-oil for 3.5 hr/d, 4 days/wk for either 4 or 13 wk. Following the acute (4 wk) exposure to 1.5 mg/1, a multifocal pneumonitis was observed. Lung lavage fluid had an elevated number of polymorphonuclear leukocytes, a...

  18. Acute Arterial Emergencies

    PubMed Central

    Dagnone, L. E.; Brown, P. M.

    1983-01-01

    The response of the primary care physician in the initial assessment and management of acute arterial injuries will often be the deciding factor in survival of life, limb or organ system. Most arterial emergencies occur as a result of trauma, disruption of vessel wall and/or occlusion of flow. The common clinical syndromes of acute arterial emergencies are injuries to and beyond the aorta, acute aortic dissection, ruptured aortic aneurysm, and thromboembolic occlusive arterial disease. The role of arteriography and the urgency of definitive surgical repair in acute arterial emergencies is summarized. PMID:21283323

  19. Intra-Peritoneal Administration of Mitochondrial DNA Provokes Acute Lung Injury and Systemic Inflammation via Toll-Like Receptor 9.

    PubMed

    Zhang, Lemeng; Deng, Songyun; Zhao, Shuangping; Ai, Yuhang; Zhang, Lina; Pan, Pinhua; Su, Xiaoli; Tan, Hongyi; Wu, Dongdong

    2016-01-01

    The pathogenesis of sepsis is complex. Mitochondrial dysfunction, which is responsible for energy metabolism, intrinsic apoptotic pathway, oxidative stress, and systemic inflammatory responses, is closely related with severe sepsis induced death. Mitochondria DNA (mtDNA) contain un-methylated cytosine phosphate guanine (CpG) motifs, which exhibit immune stimulatory capacities. The aim of this study was to investigate the role and mechanism of mtDNA release on lipopolysaccharide (LPS) induced acute lung injury (ALI) and systemic inflammation. Following LPS injection, plasma mtDNA copies peak at 8 h. Compared with wild-type (WT) mice, mtDNA in toll like receptor 4 knockout (TLR4 KO) mice were significantly decreased. MtDNA intra-peritoneal administration causes apparent ALI as demonstrated by increased lung injury score, bronchoalveolar lavage fluid (BALF) total protein and wet/dry (W/D) ratio; mtDNA injection also directly provokes systemic inflammation, as demonstrated by increased IL-1β, IL-6, high-mobility group protein B1 (HMGB1) level; while nuclear DNA (nDNA) could not induce apparent ALI and systemic inflammation. However, compared with WT mice, TLR4 KO could not protect from mtDNA induced ALI and systemic inflammation. Specific TLR9 inhibitor, ODN 2088 pretreatment can significantly attenuate mtDNA induced ALI and systemic inflammation, as demonstrated by improved lung injury score, decreased lung wet/dry ratio, BALF total protein concentration, and decreased systemic level of IL-1β, IL-6 and HMGB1. MtDNA administration activates the expression of p-P38 mitogen-activated protein kinases (MAPK) in lung tissue and specific TLR9 inhibitor pretreatment can attenuate this activation. Thus, LPS-induced mtDNA release occurs in a TLR4-dependent manner, and mtDNA causes acute lung injury and systemic inflammation in a TLR9-dependent and TLR4-independent manner. PMID:27589725

  20. Poznan acute Astronomical Observatory

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    This Poznan acute Astronomical Observatory is a unit of the Adam Mickiewicz University, located in Poznan acute, Poland. From its foundation in 1919, it has specialized in astrometry and celestial mechanics (reference frames, dynamics of satellites and small solar system bodies). Recently, research activities have also included planetary and stellar astrophysics (asteroid photometry, catalysmic b...

  1. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on behavior

    SciTech Connect

    Mullenix, P.J.; Kernan, W.J.; Tassinari, M.S.; Schunior, A.; Waber, D.P.; Howes, A.; Tarbell, N.J. )

    1990-10-15

    Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy.

  2. Fever and increased serum IL-1 activity as a systemic manifestation of acute phototoxicity in New Zealand White rabbits.

    PubMed

    Ansel, J C; Luger, T A; Green, I

    1987-07-01

    Ultraviolet (UV) radiation is a significant environmental hazard for humans and animals. Although the clinical effect of an acute UV exposure such as cutaneous inflammation, malaise, somnolence, chills, and fever have been appreciated for many years, the underlying mechanisms mediating these effects are poorly understood. Since chills and fever are the most dramatic systemic sequelae after a prolonged exposure to UV, we specifically examined the effect of whole-body UV irradiation on core body temperature and serum endogenous pyrogen activity of New Zealand White rabbits, correlating this with serum interleukin 1 (IL-1) activity and alterations of serum divalent cation levels. We found that an acute dose of UV irradiation (Westinghouse FS-40 lamps, 0.2 mJ/cm2/s X 8 h) resulted in a significant increase in the core body temperature 2 h post UV (0.8 degree C), peaking 5 h post UV (1.8 degree C), and returning to normal 24 h post UV. Likewise, the sera from the UV-irradiated rabbits had significant endogenous pyrogen activity when transferred into naive recipient animals, causing an increase in core body temperature within 45 min (0.65 +/- 0.12 degree C), decreasing over the next 2 h, and returning to normal 6 h post injection. No endotoxin contamination was detected in any serum samples. This post-UV febrile response was accompanied by a prolonged increase in serum IL-1 activity (5-10 X) and a significant alteration in serum divalent cation levels, with the rabbits becoming euthermic even as the serum IL-1 levels remained elevated. These findings provide new information concerning the pathogenesis and kinetics of these systemic effects after an acute dose of UV irradiation. PMID:3496401

  3. Successful management of acute respiratory failure in an Idiopathic Pulmonary Fibrosis patient using an extracorporeal carbon dioxide removal system.

    PubMed

    Vianello, Andrea; Arcaro, Giovanna; Paladini, Luciana; Iovino, Silvia

    2016-01-01

    Patients with Idiopathic Pulmonary Fibrosis (IPF) requiring Invasive Mechanical Ventilation (IMV) following unsuccessful treatment with Non-Invasive Ventilation (NIV) have a high mortality rate. IMV is, moreover, an independent predictor of poor outcome during the post-transplantation period in patients on waiting lists for Lung Transplantation (LT). Here we describe the successful management of an IPF patient with acute respiratory failure (ARF) using a pump-assisted veno-venous system for extracorporeal CO2 removal (ECCO2R) (ProLUNG® system) as an alternative to endotracheal intubation (ETI) following NIV failure. Given this positive experience, further studies are warranted focusing on the ECCO2R system's tolerability, safety, and efficacy in patients with IPF and severe ARF in whom NIV alone is ineffective. PMID:27537725

  4. CCL5-glutamate interaction in central nervous system: Early and acute presynaptic defects in EAE mice.

    PubMed

    Di Prisco, Silvia; Merega, Elisa; Milanese, Marco; Summa, Maria; Casazza, Simona; Raffaghello, Lizzia; Pistoia, Vito; Uccelli, Antonio; Pittaluga, Anna

    2013-12-01

    We investigated the CCL5-glutamate interaction in the cortex and in the spinal cord from mice with Experimental Autoimmune Encephalomyelitis (EAE) at 13 and 21/30 days post immunization (d.p.i.), representing the onset and the peak of the disease, respectively. An early reduction of the KCl-evoked glutamate release was observed in cortical terminals from EAE mice at 13 d.p.i., persisting until 21/30 d.p.i. A concomitant reduction of the depolarization-evoked cyclic adenosine monophosphate (cAMP), but not of the inositol 1,4,5-trisphosphate (IP3) cortical production also occurred at 13 d.p.i, that still was detectable at the acute stage of disease (21 dp.i.). Inasmuch, the CCL5-mediated inhibition of glutamate exocytosis observed in control mice turned to facilitation in EAE mouse cortex at 13 d.p.i., then becoming undetectable at 21/30 d.p.i. Differently, glutamate exocytosis, as well as IP3 and cAMP productions were unaltered in spinal cord synaptosomes from EAE mice at 13 d.p.i., but significantly increased at 21/30 d.p.i., while the presynaptic CCL5-mediated facilitation of glutamate exocytosis observed in control mice remained unchanged. In both CNS regions, the presynaptic defects were parallelled by increased CCL5 availability. Inasmuch, the presynaptic defects so far described in EAE mice were reminiscent of the effects acute CCL5 exerts in control conditions. Based on these observations we propose that increased CCL5 bioavailability could have a role in determining the abovedescribed impaired presynaptic impairments in both CNS regions. These presynaptic defects could be relevant to the onset of early cognitive impairments and acute neuroinflammation and demyelinating processes observed in multiple sclerosis patients. PMID:23958452

  5. Plasticity of the Systemic Inflammatory Response to Acute Infection during Critical Illness: Development of the Riboleukogram

    PubMed Central

    Burykin, Anton; Ruan, Jianhua; Li, Qing; Schierding, William; Lin, Nan; Dixon, David; Zhang, Weixiong; Coopersmith, Craig M.; Dunne, W. Michael; Colonna, Marco; Ghosh, Bijoy K.; Cobb, J. Perren

    2008-01-01

    Background Diagnosis of acute infection in the critically ill remains a challenge. We hypothesized that circulating leukocyte transcriptional profiles can be used to monitor the host response to and recovery from infection complicating critical illness. Methodology/Principal Findings A translational research approach was employed. Fifteen mice underwent intratracheal injections of live P. aeruginosa, P. aeruginosa endotoxin, live S. pneumoniae, or normal saline. At 24 hours after injury, GeneChip microarray analysis of circulating buffy coat RNA identified 219 genes that distinguished between the pulmonary insults and differences in 7-day mortality. Similarly, buffy coat microarray expression profiles were generated from 27 mechanically ventilated patients every two days for up to three weeks. Significant heterogeneity of VAP microarray profiles was observed secondary to patient ethnicity, age, and gender, yet 85 genes were identified with consistent changes in abundance during the seven days bracketing the diagnosis of VAP. Principal components analysis of these 85 genes appeared to differentiate between the responses of subjects who did versus those who did not develop VAP, as defined by a general trajectory (riboleukogram) for the onset and resolution of VAP. As patients recovered from critical illness complicated by acute infection, the riboleukograms converged, consistent with an immune attractor. Conclusions/Significance Here we present the culmination of a mouse pneumonia study, demonstrating for the first time that disease trajectories derived from microarray expression profiles can be used to quantitatively track the clinical course of acute disease and identify a state of immune recovery. These data suggest that the onset of an infection-specific transcriptional program may precede the clinical diagnosis of pneumonia in patients. Moreover, riboleukograms may help explain variance in the host response due to differences in ethnic background, gender, and

  6. Argon laser peripheral iridoplasty versus systemic intraocular pressure-lowering medications as immediate management for acute phacomorphic angle closure

    PubMed Central

    Lee, Jacky WY; Lai, Jimmy SM; Yick, Doris WF; Yuen, Can YF

    2013-01-01

    Background The purpose of this study was to compare the efficacy and safety of argon laser peripheral iridoplasty (ALPI) and systemic intraocular pressure (IOP)-lowering medications in the immediate management of acute phacomorphic angle closure. Methods Consecutive cases of acute phacomorphic angle closure were randomized to receive ALPI and an intravenous or oral carbonic anhydrase inhibitor as initial treatment. Intravenous mannitol was administered for presenting IOP > 60 mmHg or IOP > 40 mmHg 2 hours posttreatment in both arms. Results Of 10 consecutive cases, six received medical therapy and four received ALPI. Fifty percent in the medical group and none in the ALPI group required intravenous mannitol. The ALPI group took less time to achieve IOP < 25 mmHg (18.8 ± 7.5 minutes versus 115.0 ± 97.0 minutes, P = 0.001, F test); had a greater IOP reduction within 30 minutes (69.8% ± 7.7% versus 40.9 ± 23.9%, P = 0.03, t-test); and had a consistently smaller post-attack cup to disc ratio (0.50 ± 0.02 versus 0.60 ± 0.20, P = 0.002, F test). Conclusion ALPI offers greater safety, consistency, and efficacy than systemic IOP-lowering medications as initial treatment for phacomorphic angle closure. PMID:23326185

  7. Autonomous system for cross-organ investigation of ethanol-induced acute response in behaving larval zebrafish.

    PubMed

    Lin, Xudong; Li, Vincent W T; Chen, Siya; Chan, Chung-Yuen; Cheng, Shuk-Han; Shi, Peng

    2016-03-01

    Ethanol is widely consumed and has been associated with various diseases in different organs. It is therefore important to study ethanol-induced responses in living organisms with the capability to address specific organs in an integrative manner. Here, we developed an autonomous system based on a series of microfluidic chips for cross-organ investigation of ethanol-induced acute response in behaving larval zebrafish. This system enabled high-throughput, gel-free, and anesthetic-free manipulation of larvae, and thus allowed real-time observation of behavioral responses, and associated physiological changes at cellular resolution within specific organs in response to acute ethanol stimuli, which would otherwise be impossible by using traditional methods for larva immobilization and orientation. Specifically, three types of chips ("motion," "lateral," and "dorsal"), based on a simple hydrodynamic design, were used to perform analysis in animal behavior, cardiac, and brain physiology, respectively. We found that ethanol affected larval zebrafish in a dose-dependent manner. The motor function of different body parts was significantly modulated by ethanol treatment, especially at a high dose of 3%. These behavioral changes were temporally associated with a slow-down of heart-beating and a stereotyped activation of certain brain regions. As we demonstrated in this proof-of-concept study, this versatile Fish-on-Chip platform could potentially be adopted for systematic cross-organ investigations involving chemical or genetic manipulations in zebrafish model. PMID:27158291

  8. Systemic inflammatory response syndrome in nonhuman primates culminating in multiple organ failure, acute lung injury, and disseminated intravascular coagulation.

    PubMed

    Hukkanen, Renee R; Liggitt, H Denny; Murnane, Robert D; Frevert, Charles W

    2009-10-01

    The systemic inflammatory response syndrome (SIRS) is a clinicopathological manifestation of overexuberant acute-phase inflammation caused by infectious or noninfectious etiologies. The systemic release of pro-inflammatory cytokines, chemokines, and lipid and vasoactive mediators induces endothelial damage and microvascular thrombosis, potentially culminating in disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), and multiple organ dysfunction (MOD) or failure (MOF). We present five cases in the pig-tailed macaque and olive baboon where SIRS resulted in MOF, ARDS, DIC, and the Waterhouse-Friderichsen syndrome; each with gross and histological elements manifested as edema, deposition of fibrin, hemorrhage, and thrombosis. In the described cases, SIRS was the end-common pathway for multiple risk factors that parallel those documented in humans: major surgery, obstetric complications, and infection. The diagnosis of SIRS should be considered when evaluating nonhuman primate (NHP) cases of MOF manifesting with histological evidence of vascular leakage. Experimental manipulation of NHP models may be complicated by SIRS and accompanying rapid clinical decompensation. Such adverse events may compromise toxicological studies and should be avoided when possible. PMID:19773593

  9. [Use of steam-oxygen tents with a universal steam generator and automatic control system in the treatment of acute stenosing laryngotracheitis in children].

    PubMed

    Taĭts, B M

    1993-01-01

    To treat acute stenosing laryngotracheitis in acute respiratory viral infection in children an original method has been developed and used for 2 years in a special hospital department. The method implies treatment of children in steam-and-oxygen tents with a universal steam-moistening generator and automatic control system. A controlled study of 50 children with acute laryngeal stenosis degree I-III confirmed high efficacy of this method permitting improvement of blood oxygenation, gas composition, acid-base condition, reduction of acidosis, prevention of exicosis and brain edema. Warm humid atmosphere promoted better discharge of the secretion and better functioning of the ciliated epithelium. Combined treatment incorporating the tents in acute laryngeal stenoses reduced lethality in severe cases, number of intubations and tracheostomies, of complications resultant from parenteral administration of the drugs. PMID:8009767

  10. Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash

    SciTech Connect

    Marchini, T.; Magnani, N.D.; Paz, M.L.; Vanasco, V.; Tasat, D.; González Maglio, D.H.; and others

    2014-01-15

    It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5 h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1 h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3 h. The onset of an adaptive response was observed at 5 h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation. - Highlights: • An acute exposure to ROFA triggers the occurrence of systemic oxidative stress. • Changes in plasmatic oxidative stress markers appear as early as 1 h after exposure. • ROFA induces proinflammatory cytokines release and intravascular leukocyte activation. • PMN

  11. Adequate Systemic Perfusion Maintained by a CentriMag during Acute Heart Failure

    PubMed Central

    Favaloro, Roberto R.; Bertolotti, Alejandro; Diez, Mirta; Favaloro, Liliana; Gomez, Carmen; Peradejordi, Margarita; Trentadue, Julio; Hellman, Lorena; Arzani, Yanina; Otero, Pilar Varela

    2008-01-01

    Mechanical circulatory support during severe acute heart failure presents options for myocardial recovery or cardiac replacement. Short-term circulatory support with the newest generation of magnetically levitated centrifugal-flow pumps affords several potential advantages. Herein, we present our experience with such a pump—the CentriMag® (Levitronix LLC; Waltham, Mass) centrifugal-flow ventricular assist device—in 4 critically ill patients who were in cardiogenic shock. From November 2007 through March 2008, 3 patients were supported after cardiac surgery, and 1 after chronic heart failure worsened. Two patients were bridged to heart transplantation, and 2 died during support. Perfusion during support was evaluated in terms of serum lactic acid levels and oxygenation values. In all of the patients, the CentriMag's pump flow was adequate, and continuous mechanical ventilation support was provided. Lactic acid levels substantially improved with CentriMag support and were maintained at near-normal levels throughout. At the same time, arterial pH, PO2, and carbon dioxide levels remained within acceptable ranges. No thromboembolic events or mechanical failures occurred. Our experience indicates that short-term use of the CentriMag ventricular assist device during acute heart failure can restore and adequately support circulation until recovery or until the application of definitive therapy. PMID:18941648

  12. Acute Bronchitis

    MedlinePlus

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis ...

  13. The habitus of 'rescue' and its significance for implementation of rapid response systems in acute health care.

    PubMed

    Mackintosh, Nicola; Humphrey, Charlotte; Sandall, Jane

    2014-11-01

    The need to focus on patient safety and improve the quality and consistency of medical care in acute hospital settings has been highlighted in a number of UK and international reports. When patients on a hospital ward become acutely unwell there is often a window of opportunity for staff, patients and relatives to contribute to the 'rescue' process by intervening in the trajectory of clinical deterioration. This paper explores the social and institutional processes associated with the practice of rescue, and implications for the implementation and effectiveness of rapid response systems (RRSs) within acute health care. An ethnographic case study was conducted in 2009 in two UK hospitals (focussing on the medical directorates in each organisation). Data collection involved 180 h of observation, 35 staff interviews (doctors, nurses, health care assistants and managers) and documentary review. Analysis was informed by Bourdieu's logic of practice and his relational concept of the 'field' of the general medical ward. Three themes illustrated the nature of rescue work within the field and collective rules which guided associated occupational distinction practices: (1) the 'dirty work' of vital sign recording and its distinction from diagnostic (higher order) interpretive work; (2) the moral order of legitimacy claims for additional help; and (3) professional deference and the selective managerial control of rescue work. The discourse of rescue provided a means of exercising greater control over clinical uncertainty. The acquisition of 'rescue capital' enabled the social positioning of health care assistants, nurses and doctors, and shaped use of the RRS on the wards. Boundary work, professional legitimation and jurisdictional claims defined the social practice of rescue, as clinical staff had to balance safety, professional and organisational concerns within the field. This paper offers a nuanced understanding of patient safety on the front-line, challenging notions of

  14. Exacerbation of acute kidney injury by bone marrow stromal cells from rats with persistent renin-angiotensin system activation.

    PubMed

    Kankuri, Esko; Mervaala, Elina E; Storvik, Markus; Ahola, Aija M J; Levijoki, Jouko; Müller, Dominik N; Finckenberg, Piet; Mervaala, Eero M

    2015-06-01

    Hypertension and persistent activation of the renin-angiotensin system (RAS) are predisposing factors for the development of acute kidney injury (AKI). Although bone-marrow-derived stromal cells (BMSCs) have shown therapeutic promise in treatment of AKI, the impact of pathological RAS on BMSC functionality has remained unresolved. RAS and its local components in the bone marrow are involved in several key steps of cell maturation processes. This may also render the BMSC population vulnerable to alterations even in the early phases of RAS pathology. We isolated transgenic BMSCs (TG-BMSCs) from young end-organ-disease-free rats with increased RAS activation [human angiotensinogen/renin double transgenic rats (dTGRs)] that eventually develop hypertension and die of end-organ damage and kidney failure at 8 weeks of age. Control cells (SD-BMSCs) were isolated from wild-type Sprague-Dawley rats. Cell phenotype, mitochondrial reactive oxygen species (ROS) production and respiration were assessed, and gene expression profiling was carried out using microarrays. Cells' therapeutic efficacy was evaluated in a rat model of acute ischaemia/reperfusion-induced AKI. Serum urea and creatinine were measured at 24 h and 48 h. Acute tubular damage was scored and immunohistochemistry was used for evaluation for markers of inflammation [monocyte chemoattractant protein (MCP-1), ED-1], and kidney injury [kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL)]. TG-BMSCs showed distinct mitochondrial morphology, decreased cell respiration and increased production of ROS. Gene expression profiling revealed a pronounced pro-inflammatory phenotype. In contrast with the therapeutic effect of SD-BMSCs, administration of TG-BMSCs in the AKI model resulted in exacerbation of kidney injury and high mortality. Our results demonstrate that early persistent RAS activation can dramatically compromise therapeutic potential of BMSCs by causing a shift into a pro

  15. The iontophoretic transdermal system formulation of sumatriptan as a new option in the acute treatment of migraine: a perspective.

    PubMed

    Vikelis, Michail; Spingos, Konstantinos C; Rapoport, Alan M

    2015-07-01

    An iontophoretic transdermal system (ITS) (skin patch) formulation of sumatriptan for the acute treatment of migraine attacks was approved by the US Food and Drug Administration in January 2013. This transdermal system bypasses the gastrointestinal tract, as it uses low electrical current to move sumatriptan transdermally into the subcutaneous tissue. Randomized, double-blind, controlled clinical trials have demonstrated minimal triptan-related side effects and superior efficacy versus placebo, comparable with other sumatriptan formulations. Sumatriptan ITS can be applied successfully during a mild or severe migraine attack. According to pharmacokinetic properties and clinical data, sumatriptan ITS may be a good choice for people with migraine and severe nausea, vomiting or gastroparesis, those with intolerable triptan-related adverse events and those not responding optimally to oral medications. PMID:26136843

  16. The iontophoretic transdermal system formulation of sumatriptan as a new option in the acute treatment of migraine: a perspective

    PubMed Central

    Spingos, Konstantinos C.; Rapoport, Alan M.

    2015-01-01

    An iontophoretic transdermal system (ITS) (skin patch) formulation of sumatriptan for the acute treatment of migraine attacks was approved by the US Food and Drug Administration in January 2013. This transdermal system bypasses the gastrointestinal tract, as it uses low electrical current to move sumatriptan transdermally into the subcutaneous tissue. Randomized, double-blind, controlled clinical trials have demonstrated minimal triptan-related side effects and superior efficacy versus placebo, comparable with other sumatriptan formulations. Sumatriptan ITS can be applied successfully during a mild or severe migraine attack. According to pharmacokinetic properties and clinical data, sumatriptan ITS may be a good choice for people with migraine and severe nausea, vomiting or gastroparesis, those with intolerable triptan-related adverse events and those not responding optimally to oral medications. PMID:26136843

  17. Acute Flaccid Myelitis

    MedlinePlus

    ... on Facebook Tweet Share Compartir Acute flaccid myelitis (AFM) is a condition that affects the nervous system, ... from a variety of causes including viral infections. AFM is characterized by a sudden weakness in one ...

  18. Reduced acute inpatient care was largest savings component of Geisinger Health System's patient-centered medical home.

    PubMed

    Maeng, Daniel D; Khan, Nazmul; Tomcavage, Janet; Graf, Thomas R; Davis, Duane E; Steele, Glenn D

    2015-04-01

    Early evidence suggests that the patient-centered medical home has the potential to improve patient outcomes while reducing the cost of care. However, it is unclear how this care model achieves such desirable results, particularly its impact on cost. We estimated cost savings associated with Geisinger Health System's patient-centered medical home clinics by examining longitudinal clinic-level claims data from elderly Medicare patients attending the clinics over a ninety-month period (2006 through the first half of 2013). We also used these data to deconstruct savings into its main components (inpatient, outpatient, professional, and prescription drugs). During this period, total costs associated with patient-centered medical home exposure declined by approximately 7.9 percent; the largest source of this savings was acute inpatient care ($34, or 19 percent savings per member per month), which accounts for about 64 percent of the total estimated savings. This finding is further supported by the fact that longer exposure was also associated with lower acute inpatient admission rates. The results of this study suggest that patient-centered medical homes can lead to sustainable, long-term improvements in patient health outcomes and the cost of care. PMID:25847647

  19. Automation of an in vitro cytotoxicity assay used to estimate starting doses in acute oral systemic toxicity tests.

    PubMed

    Bouhifd, Mounir; Bories, Gilles; Casado, Juan; Coecke, Sandra; Norlén, Hedvig; Parissis, Nicholaos; Rodrigues, Robim M; Whelan, Maurice P

    2012-06-01

    Application of High Throughput Screening (HTS) to the regulatory safety assessment of chemicals is still in its infancy but shows great promise in terms of facilitating better understanding of toxicological modes-of-action, reducing the reliance on animal testing, and allowing more data-poor chemicals to be assessed at a reasonable cost. To promote the uptake and acceptance of HTS approaches, we describe in a stepwise manner how a well known cytotoxicity assay can be automated to increase throughput while maintaining reliability. Results generated with selected reference chemicals compared very favourably with data obtained from a previous international validation study concerning the prediction of acute systemic toxicity in rodents. The automated assay was then included in a formal ECVAM validation study to determine if the assay could be used for binary classification of chemicals with respect to their acute oral toxicity, using a threshold equivalent to a dose of 2000 mg/kg b.w. in a rodent bioassay (LD50). This involved the blind-testing of 56 reference chemicals on the HTS platform to produce concentration-response and IC50 data. Finally, the assay was adapted to a format more suited to higher throughput testing without compromising the quality of the data obtained. PMID:22465836

  20. [A rare case of an acute abdomen patient with gangrene of the colon as a complication of systemic lupus erythematosus].

    PubMed

    Dolák, S; Prochotský, A; Mifkovič, A; Škultéty, J; Ježovít, M; Koudelka, P; Bluska, P

    2015-02-01

    The authors present a case report of a 39-year-old woman with acute abdomen - a comorbid patient with systemic lupus erythematosus, chronic renal insufficiency as a complication of lupus nephritis, included in a haemodialysis programme. The patient had also undergone transplantation of the left kidney in the past. She was initially admitted to the Department of Traumatology for a total endoprosthesis procedure due to bionecrosis of the head of the thigh bone. Postoperatively, the patients condition was complicated by gangrene of the colon confirmed by CT scan and during the operation. The patient was operated on - subtotal colectomy, terminal ileostomy and left-sided ovariectomy was performed. The postoperative course was complicated by perforation of the jejunum which was sutured. The patient was admitted to ICU and, after recovery, to our surgical department. Because of the metabolic disturbance she was treated in the internal medicine department. After 60 days she was discharged in a good condition, walking and with full per os realimentation.Key words: lupus erythematosus gangrene of the colon acute abdomen. PMID:25659257

  1. [Effect of tricarboxylic acid cycle intermediates on nitric oxide system during acute hypoxia].

    PubMed

    Kurhaliuk, N M

    2002-01-01

    Effects Crebs Cycle of exogenous intermediates sodium succinate (50 mg/kg) and sodium alpha-ketoglutarate (200 mg/kg) on processes of mitochondrial ADP-stimulated respiration (using as substrates of oxidation 0.35 mM succinate, 1 mM alpha-ketoglutarate), production of nitric oxide under NO2-, NO3-, as well as carbamide, putrescyne content and processes of lipid peroxidation in the rats liver under acute hypoxia (7% O2 in N2, 30 min) have been studied. It was shown, that the exogenous sodium alpha-ketoglutarate increases nitric oxide content, aminotransferase activation, inhibition of succinatedehydrogenase simultaneously more than exogenous sodium succinate. It correlates with decreasing of processes lipid peroxidation in liver. PMID:14964867

  2. [Acute myocarditis].

    PubMed

    Combes, Alain

    2012-06-01

    Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Acute myocarditis must be considered in patients who present with recent-onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackievirus and adenovirus being the most frequently viruses responsible for the disease. Treatment of myocarditis remains largely supportive, since immunosuppression has not been proven to be beneficial for acute lymphocytic myocarditis. Trials of antiviral therapies, or immunostimulants such as interferons, suggest a potential therapeutic role but require further investigation. Lastly, early recognition of patients rapidly progressing to refractory cardiac failure and their immediate transfer to a medical-surgical center experienced in mechanical circulatory support is warranted. In this setting, ECMO should be the first-line mechanical assistance. For highly unstable patients, a Mobile Cardiac Assistance Unit, that rapidly travels to primary care hospitals with a portable ECMO system and hooks it up before refractory multiorgan failure takes hold, is the preferred option. PMID:22515999

  3. [Acute myocarditis].

    PubMed

    Combes, Alain

    2013-05-01

    Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Acute myocarditis must be considered in patients who present with recent onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackievirus and adenovirus being the most frequently viruses responsible for the disease. Treatment of myocarditis remains largely supportive, since immunosuppression has not been proven to be beneficial for acute lymphocytic myocarditis. Trials of antiviral therapies, or immunostimulants such as interferons, suggest a potential therapeutic role but require further investigation. Lastly, early recognition of patients rapidly progressing to refractory cardiac failure and their immediate transfer to a medical-surgical center experienced in mechanical circulatory support is warranted. In this setting, ECMO should be the first-line mechanical assistance. For highly unstable patients, a Mobile Cardiac Assistance Unit, that rapidly travels to primary care hospitals with a portable ECMO system and hooks it up before refractory multiorgan failure takes hold, is the preferred option. PMID:23789482

  4. A scoring system for assessing the severity of acute diarrhea of adult patients

    PubMed Central

    Xiao, Hong-li; Ma, Su-xia; Qi, Hai-yu; Li, Xiaoli; Wang, Yan; Yin, Cheng-hong

    2016-01-01

    BACKGROUND: Diarrhea is frequently seen in developed and developing countries, and severe diarrhea is characterized by the high risk of death. Thus, it is very important to assess the severity of diarrhea early. We conducted a multi-center study to identify risk factors for the severity of diarrhea in adult patients and formulate an adult diarrhea state score (ADSS) for out-patient clinicians. METHODS: A total of 219 adult patients with acute diarrhea were divided into two groups: 132 patients with mild diarrhea and 87 with severe diarrhea. Logistic regression was used to determine risk factors for the severity of diarrhea. The risk factors were assessed and an ADSS was formulated. Receiver operating characteristic (ROC) analysis was made to evaluate the diagnostic accuracy of ADSS, and the Kappa test was used to confirm the diagnostic reliability. RESULTS: Five risk factors for evaluating the severity of diarrhea in adults included age (P<0.05), axillary temperature (P<0.01), mean arterial pressure (P<0.01), white blood cell count (WBC; P<0.01), and WBC in stool (P<0.01). The area under the ROC curve for ADSS was 0.958 when the cut off value was 4 (a sensitivity of 0.909; a specificity of 0.874), and the Kappa value was 0.781 (P<0.05). CONCLUSION: The risk factors associated with the pathogenic condition of diarrhea were identified, quantified and formulated into an ADSS, which has high diagnostic accuracy and reliability for the early identification of patients with severe acute diarrhea. PMID:27313808

  5. A computer-aided detection (CAD) system with a 3D algorithm for small acute intracranial hemorrhage

    NASA Astrophysics Data System (ADS)

    Wang, Ximing; Fernandez, James; Deshpande, Ruchi; Lee, Joon K.; Chan, Tao; Liu, Brent

    2012-02-01

    Acute Intracranial hemorrhage (AIH) requires urgent diagnosis in the emergency setting to mitigate eventual sequelae. However, experienced radiologists may not always be available to make a timely diagnosis. This is especially true for small AIH, defined as lesion smaller than 10 mm in size. A computer-aided detection (CAD) system for the detection of small AIH would facilitate timely diagnosis. A previously developed 2D algorithm shows high false positive rates in the evaluation based on LAC/USC cases, due to the limitation of setting up correct coordinate system for the knowledge-based classification system. To achieve a higher sensitivity and specificity, a new 3D algorithm is developed. The algorithm utilizes a top-hat transformation and dynamic threshold map to detect small AIH lesions. Several key structures of brain are detected and are used to set up a 3D anatomical coordinate system. A rule-based classification of the lesion detected is applied based on the anatomical coordinate system. For convenient evaluation in clinical environment, the CAD module is integrated with a stand-alone system. The CAD is evaluated by small AIH cases and matched normal collected in LAC/USC. The result of 3D CAD and the previous 2D CAD has been compared.

  6. Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes

    PubMed Central

    Manzanares, J; Julian, MD; Carrascosa, A

    2006-01-01

    Cannabis extracts and synthetic cannabinoids are still widely considered illegal substances. Preclinical and clinical studies have suggested that they may result useful to treat diverse diseases, including those related with acute or chronic pain. The discovery of cannabinoid receptors, their endogenous ligands, and the machinery for the synthesis, transport, and degradation of these retrograde messengers, has equipped us with neurochemical tools for novel drug design. Agonist-activated cannabinoid receptors, modulate nociceptive thresholds, inhibit release of pro-inflammatory molecules, and display synergistic effects with other systems that influence analgesia, especially the endogenous opioid system. Cannabinoid receptor agonists have shown therapeutic value against inflammatory and neuropathic pains, conditions that are often refractory to therapy. Although the psychoactive effects of these substances have limited clinical progress to study cannabinoid actions in pain mechanisms, preclinical research is progressing rapidly. For example, CB1mediated suppression of mast cell activation responses, CB2-mediated indirect stimulation of opioid receptors located in primary afferent pathways, and the discovery of inhibitors for either the transporters or the enzymes degrading endocannabinoids, are recent findings that suggest new therapeutic approaches to avoid central nervous system side effects. In this review, we will examine promising indications of cannabinoid receptor agonists to alleviate acute and chronic pain episodes. Recently, Cannabis sativa extracts, containing known doses of tetrahydrocannabinol and cannabidiol, have granted approval in Canada for the relief of neuropathic pain in multiple sclerosis. Further double-blind placebo-controlled clinical trials are needed to evaluate the potential therapeutic effectiveness of various cannabinoid agonists-based medications for controlling different types of pain. PMID:18615144

  7. Myeloid leukemia risk assessment and dynamics of the granulocytopoietic system in acutely and continuously irradiated humans: modeling approach.

    PubMed

    Smirnova, O A

    2015-05-01

    A dynamic modeling approach to the risk assessment of radiogenic myeloid leukemia is proposed. A basic tool of this approach is a biologically motivated mathematical model of the granulocytopoietic system, which is capable of predicting the dynamics of blood granulocytes and bone marrow granulocytopoietic cells in acutely and chronically irradiated humans. The performed modeling studies revealed that the dose dependence of the scaled maximal concentration of bone marrow granulocytopoietic cells with radiation-induced changes, which make a cell premalignant, and the dose dependence of the scaled integral of the concentration of these cells over the period of the response of the granulocytopoietic system to acute irradiation conform to the dose dependence of excess relative risk for myeloid leukemia among atomic bomb survivors in a wide range of doses and in a range of comparatively low doses, respectively. Additionally, the dose dependence of the scaled integral of the concentration of these cells over the period of the response of the granulocytopoietic system to continuous irradiation with the dose rate and durations, which were used in brachytherapy, conforms to the dose dependence of excess relative risk for leukemia among the respective groups of exposed patients. These modeling findings demonstrate the potential to use the proposed modeling approach for predicting the excess relative risk for myeloid leukemia among humans exposed to various radiation regimes. Obviously, this is especially important in the assessment of the risks for radiogenic myeloid leukemia among people residing in contaminated areas after an accident or explosion of a radiological device, among astronauts on long-term space missions, as well as among patients treated with radiotherapy. PMID:25811147

  8. Antiphospholipid Syndrome - A Case Report of Pulmonary Thromboembolism, Followed with Acute Myocardial Infarction in Patient with Systemic Sclerosis

    PubMed Central

    Vavlukis, Marija; Kotlar, Irina; Chaparoska, Emilija; Pocesta, Bekim; Pejkov, Hristo; Boshev, Marjan; Kedev, Sasko

    2015-01-01

    AIM: We are presenting an uncommon case of pulmonary embolism, followed with an acute myocardial infarction, in a patient with progressive systemic sclerosis. CASE PRESENTATION: A female 40 years of age was admitted with signs of pulmonary embolism, confirmed with CT scan, which also reviled a thrombus in the right ventricle. The patient had medical history of systemic sclerosis since the age of 16 years. She suffered an ischemic stroke 6 years ago, but she was not taking any anticoagulant or antithrombotic medications ever since. She received a treatment with thrombolytic therapy, and subsequent UFH, but, on the second day after receiving fibrinolysis, she felt chest pain accompanied with ECG changes consistent for ST-segment elevation myocardial infarction (STEMI). Urgent coronary angiography was undertaken, which reviled cloths causing total occlusion in 4 blood vessels, followed with thromboaspiration, but without successful reperfusion. Several hours later the patient developed rapid deterioration with letal ending. During the very short hospital course, blood sampling reviled presence of antiphospholipid antibodies. CONCLUSION: The acquired antiphospholipid syndrome is common condition in patients with systemic autoimmune diseases, but relatively rare in patients with systemic sclerosis. Never the less, we have to be aware of it when treating the patients with systemic sclerosis.

  9. An exploration of the leadership attributes and methods associated with successful lean system deployments in acute care hospitals.

    PubMed

    Steed, Airica

    2012-01-01

    The lean system has been shown to be a viable and sustainable solution for the growing number of cost, quality, and efficiency issues in the health care industry. While there is a growing body of evidence to support the outcomes that can be achieved as a result of the successful application of the lean system in hospital organizations, there is not a complete understanding of the leadership attributes and methods that are necessary to achieve successful widespread mobilization and sustainment. This study was an exploration of leadership and its relevant association with successful lean system deployments in acute care hospitals. This research employed an exploratory qualitative research design encompassing a research questionnaire and telephonic interviews of 25 health care leaders in 8 hospital organizations across the United States. The results from this study identified the need to have a strong combination of personal characteristics, learned behaviors, strategies, tools, and tactics that evolved into a starting adaptable framework for health care leaders to leverage when starting their own transformational change journeys using the lean system. Health care leaders could utilize the outcomes reported in this study as a conduit to enhance the effective deployment, widespread adoption, and sustainment of the lean system in practice. PMID:22207019

  10. Massive Systemic Air Embolism during Extracorporeal Membrane Oxygenation Support of a Neonate with Acute Respiratory Distress Syndrome after Cardiac Surgery

    PubMed Central

    Timpa, Joseph G.; O’Meara, Carlisle; McILwain, R. Britt; Dabal, Robert J.; Alten, Jeffrey A.

    2011-01-01

    Abstract: Extracorporeal membrane oxygenation (ECMO) is universally accepted as a potential lifesaving therapy for neonates suffering severe cardiorespiratory failure, with survival reported as 81% weaning off ECMO and 69% to hospital discharge in this population. Although ECMO may reduce mortality in certain neonatal patients, it is associated with significant complications. Air in the circuit complicates 4.9% of neonatal ECMO runs, and it is crucial that all ECMO caregivers are trained in the prevention of air embolism and possess the knowledge necessary to efficiently identify and remove air from the ECMO circuit to prevent life threatening consequences. We present a fatal case of neonatal systemic air embolism leading to massive entrainment of air into the ECMO venous return cannula of a neonatal patient with acute respiratory distress syndrome following repair of obstructed total anomalous pulmonary venous connection. We describe the pathophysiology and presentation of this rare condition and the importance of early recognition, due to its high mortality rate. PMID:21848179

  11. Psychobiology of PTSD in the Acute Aftermath of Trauma: Integrating Research on Coping, HPA Function and Sympathetic Nervous System Activity

    PubMed Central

    Morris, Matthew C.; Rao, Uma

    2012-01-01

    Research on the psychobiological sequelae of trauma has typically focused on long-term alterations in individuals with chronic posttraumatic stress disorder (PTSD). Far less is known about the nature and course of psychobiological risk factors for PTSD during the acute aftermath of trauma. In this review, we summarize data from prospective studies focusing on the relationships among sympathetic nervous system activity, hypothalamic-pituitary-adrenal function, coping strategies and PTSD symptoms during the early recovery (or non-recovery) phase. Findings from pertinent studies are integrated to inform psychobiological profiles of PTSD-risk in children and adults in the context of existing models of PTSD-onset and maintenance. Data regarding bidirectional relations between coping strategies and stress hormones is reviewed. Limitations of existing literature and recommendations for future research are discussed. PMID:23380312

  12. The use of the BiPAP biphasic positive airway pressure system in acute spinal cord injury.

    PubMed

    Tromans, A M; Mecci, M; Barrett, F H; Ward, T A; Grundy, D J

    1998-07-01

    In recent years there has been increasing demand on our Intensive Care Unit (ICU) facilities, mainly due to improved resuscitation techniques in the pre-hospital management of spinal cord injury (SCI). This has resulted in an increasing number of high tetraplegic and paraplegic patients with respiratory problems who have survived the initial injury, but have subsequently required ventilatory support, often for several weeks. In view of the continuing pressure on ICU beds and a consequent need for alternative means of providing ventilatory support within the spinal centre rather than within the ICU setting, there was a requirement to provide a simple means of ventilatory support suitable for use within the ward setting. Ventilatory assistance using BiPAP appeared to fulfil these criteria, enabling patients to be managed at reduced cost. We present our experience using this system in 28 acute SCI patients over a 4 year period. PMID:9670384

  13. Evaluation of a stand-alone computer-aided detection system for acute intra-cranial hemorrhage in emergency environments

    NASA Astrophysics Data System (ADS)

    Fernandez, James; Deshpande, Ruchi; Wang, Ximing; Liu, Brent; Brazaitis, Michael; Munter, Fletcher; Liu, Margaret

    2011-03-01

    Acute intra-cranial hemorrhage (AIH) may result from traumatic brain injury (TBI). Successful management of AIH depends heavily on the speed and accuracy of diagnosis. Timely diagnosis in emergency environments in both civilian and military settings is difficult primarily due to severe time restraints and lack of resources. Often, diagnosis is performed by emergency physicians rather than trained radiologists. As a result, added support in the form of computer-aided detection (CAD) would greatly enhance the decision-making process and help in providing faster and more accurate diagnosis of AIH. This paper discusses the implementation of a CAD system in an emergency environment, and its efficacy in aiding in the detection of AIH.

  14. [Acute Chagas cardiopathy. A systematic study of the intracardiac excitatory-conduction and autonomic nervous systems in an autochthonous case in Acre].

    PubMed

    Rocha, A; Neves, S A; Lopes, E R; Macêdo, V de O

    1996-01-01

    The histopathology of the heart is described in an acute case of Chagas' disease (DC). Lesions involving the conducting system (SC) and the autonomic intracardiac nervous system (SNAIC) are emphasized. Light microscopy showed acute pan-carditis with plenty of Trypanosoma cruzi amastigotes within heart muscle cells. Multiple inflammatory foci were found in the SC with parasitic nests within the atrioventricular node and left his bundle. There were also severe atrial periganglionitis and perineuritis with or without peripheral involvement of those structures. Apparently there was no cardiac neuronal depopulation. The epidemiological study suggested transmission through Rhodnius pictipes. To the best of our knowledge, this is the first reported case of acute DC from the Amazonian basin with systematized microscopy study of the SC and SNAIC. PMID:8768587

  15. Extracorporeal Membrane Oxygenation as Bridge-to-Decision in Acute Heart Failure due to Systemic Light-Chain Amyloidosis

    PubMed Central

    Silva, Jennifer Mancio; Fontes-Carvalho, Ricardo; Valente, Dília; Almeida, Cristiana; Cruz, António José; Tente, David; Coelho, Henrique; Oliveira, Marco; Albuquerque, Aníbal; Ribeiro, Vasco Gama

    2015-01-01

    Patient: Female, 58 Final Diagnosis: Acute hear failure Symptoms: Dispnoea • edema • fatigue Medication: — Clinical Procedure: Bone marrow biopsy • endomyocardial biopsy • abdominal subcutaneous fat biopsy under ECMO support Specialty: Cardiology Objective: Rare disease Background: Cardiac amyloidosis results from the amyloid deposition in heart tissue, either in the context of a systemic disease or as a localized form. Several pro-amyloid proteins can produce amyloid deposits in the heart. Each of these amyloidoses has characteristic clinical (cardiac and extracardiac) features, and a specific diagnosis and treatment. Case Report: A 58-year-old woman who presented with acute heart failure and echocardiographic findings strongly suggestive of infiltrative cardiomyopathy needed percutaneous veno-arterial extracorporeal membrane oxygenation (ECMO) as bridge-to-decision. Amyloid deposition was found on endomyocardial and bone marrow biopsies. Bone marrow plasma cell infiltrate with acute renal lesion and hypercalcemia confirmed the diagnosis of multiple myeloma-associated systemic light-chain amyloidosis (AL). Refractory shock with multi-organic failure syndrome persisted and no improvements in left ventricular function and structure were seen. After extensive discussion by a multidisciplinary team, and with the patients’ family, she was not considered eligible for high-dose chemotherapy and/or autologous stem cell transplantation, heart transplantation, or sequential heart with autologous stem cell transplantation. The patient died a few hours after ECMO withdrawal. During the 14 days of ECMO support no major bleeding or thrombotic complications occurred. Conclusions: The clinician must consider a diagnosis of cardiac amyloidosis in patients with heart failure, a restrictive type of cardiomyopathy with ventricular hypertrophy in the absence of valve abnormalities, or uncontrolled arterial hypertension. Although developments in chemotherapy have greatly

  16. Acute pain.

    PubMed

    Good, M

    1999-01-01

    The review of acute pain describes the problem of unresolved pain and its effects on the neural, autonomic, and immune systems. Conceptualizations and mechanisms of pain are reviewed as well as theories of pain management. Descriptive studies of patient and nurse factors that inhibit effective pain management are discussed, followed by studies of pharmacological and nonpharmacological interventions. Critical analysis reveals that most studies were atheoretical, and therefore, this proliferation of information lacked conceptual coherence and organization. Furthermore, the nature and extent of barriers to pain management were described, but few intervention studies have been devised, as yet, to modify the knowledge, beliefs, and attitudes of nurses and patients that are barriers to pain management. Although some of the complementary therapies have sufficient research support to be used in clinical pain management, the physiological mechanisms and outcomes need to be studied. It is critical at this time to design studies of interventions to improve assessment, decision making, attentive care, and patient teaching. PMID:10418655

  17. Acute phase reaction and acute phase proteins*

    PubMed Central

    Gruys, E.; Toussaint, M.J.M.; Niewold, T.A.; Koopmans, S.J.

    2005-01-01

    A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes, negative and positive acute phase proteins (APPs) with function and associated pathology is given. It appears that APPs represent appropriate analytes for assessment of animal health. Whereas they represent non-specific markers as biological effect reactants, they can be used for assessing nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. When such acute phase index is applied to separate healthy animals from animals with some disease, much better results are obtained than with single analytes and statistically acceptable results for culling individual animals may be reached. Unfortunately at present no cheap, comprehensive and easy to use system is available for assessing various acute phase proteins in serum or blood samples at the same time. Protein microarray or fluid phase microchip technology may satisfy this need; and permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease specific variables. Applying such technology may help to solve health problems in various countries not only in animal husbandry but also in human populations. PMID:16252337

  18. Impact of integrated health system changes, accelerated due to an earthquake, on emergency department attendances and acute admissions: a Bayesian change-point analysis

    PubMed Central

    Schluter, Philip J; Hamilton, Greg J; Deely, Joanne M; Ardagh, Michael W

    2016-01-01

    Objective To chart emergency department (ED) attendance and acute admission following a devastating earthquake in 2011 which lead to Canterbury's rapidly accelerated integrated health system transformations. Design Interrupted time series analysis, modelling using Bayesian change-point methods, of ED attendance and acute admission rates over the 2008–2014 period. Setting ED department within the Canterbury District Health Board; with comparison to two other district health boards unaffected by the earthquake within New Zealand. Participants Canterbury's health system services ∼500 000 people, with around 85 000 ED attendances and 37 000 acute admissions per annum. Main outcome measures De-seasoned standardised population ED attendance and acute admission rates overall, and stratified by age and sex, compared before and after the earthquake. Results Analyses revealed five global patterns: (1) postearthquake, there was a sudden and persisting decrease in the proportion of the population attending the ED; (2) the growth rate of ED attendances per head of population did not change between the pre-earthquake and postearthquake periods; (3) postearthquake, there was a sudden and persisting decrease in the proportion of the population admitted to hospital; (4) the growth rate of hospital admissions per head of the population declined between pre-earthquake and postearthquake periods and (5) the most dramatic reduction in hospital admissions growth after the earthquake occurred among those aged 65+ years. Extrapolating from the projected and fitted deseasoned rates for December 2014, ∼676 (16.8%) of 4035 projected hospital admissions were avoided. Conclusions While both necessarily and opportunistically accelerated, Canterbury's integrated health systems transformations have resulted in a dramatic and sustained reduction in ED attendances and acute hospital admissions. This natural intervention experiment, triggered by an earthquake, demonstrated that

  19. Acute effects of whole-body proton irradiation on the immune system of the mouse

    NASA Technical Reports Server (NTRS)

    Kajioka, E. H.; Andres, M. L.; Li, J.; Mao, X. W.; Moyers, M. F.; Nelson, G. A.; Slater, J. M.; Gridley, D. S.

    2000-01-01

    The acute effects of proton whole-body irradiation on the distribution and function of leukocyte populations in the spleen and blood were examined and compared to the effects of photons derived from a (60)Co gamma-ray source. Adult female C57BL/6 mice were exposed to a single dose (3 Gy at 0.4 Gy/min) of protons at spread-out Bragg peak (SOBP), protons at the distal entry (E) region, or gamma rays and killed humanely at six different times thereafter. Specific differences were noted in the results, thereby suggesting that the kinetics of the response may be variable. However, the lack of significant differences in most assays at most times suggests that the RBE for both entry and peak regions of the Bragg curve was essentially 1.0 under the conditions of this study. The greatest immunodepression was observed at 4 days postexposure. Flow cytometry and mitogenic stimulation analyses of the spleen and peripheral blood demonstrated that lymphocyte populations differ in radiosensitivity, with B (CD19(+)) cells being most sensitive, T (CD3(+)) cells being moderately sensitive, and natural killer (NK1.1(+)) cells being most resistant. B lymphocytes showed the most rapid recovery. Comparison of the T-lymphocyte subsets showed that CD4(+) T helper/inducer cells were more radiosensitive than the CD8(+) T cytotoxic/suppressor cells. These findings should have an impact on future studies designed to maximize protection of normal tissue during and after proton-radiation exposure.

  20. A case of central nervous system relapse in acute promyelocytic leukemia.

    PubMed

    Hasuike, Yuhei; Yamaguchi, Hiroshi; Mitsui, Hideki; Nishikawa, Yoshiro; Sugai, Fuminobu

    2016-04-28

    A 70-year-old woman who have achieved complete remission (CR) of acute promyelocytic leukemia (APL) with all-trans retinoic acid and chemotherapy presented with abnormal sensation in the right lateral thigh and the bilateral legs. In addition, neurological examination revealed weakness of the left shoulder abduction, the right hand, and the bilateral lower limbs. Atypical promyelocytes were detected in the cerebrospinal fluid, in spite of normal finding in the peripheral blood smear. Magnetic resonance imaging showed gadolinium-enhanced multiple intradural/extramedullary lesions in the whole spine. Nerve conduction studies of the right limbs revealed sensorimotor conduction abnormalities, conspicuously in the posterior tibial and sural nerves. As a result, she was diagnosed as having intrathecal relapse of APL, associated with multiple mononeuropathy. The neurological symptoms were completely disappeared by intrathecal chemotherapy and whole-spine radiotherapy, suggesting that the neuropathy was possibly caused by meningeal infiltration affecting multiple spinal nerve roots. Since extramedullary or intrathecal relapse is extremely rare in APL compared with other types of leukemia, precise neurological evaluations and suitable treatment should be performed immediately, when APL patients with CR manifest some neurological symptoms. PMID:27025992

  1. Evaluation of negative pressure vacuum-assisted system in acute and chronic wounds closure: our experience.

    PubMed

    Chiummariello, S; Guarro, G; Pica, A; Alfano, C

    2012-10-01

    Negative-pressure therapy or vacuum-assisted closure (VAC) has been used in clinical applications since the 1940's and has increased in popularity over the past decade. This dressing technique consists of an open cell foam dressing put into the wound cavity, a vacuum pump produces a negative pressure and an adhesive drape. A controlled sub atmospheric pressure from 75 to 150 mmHg is applied. The vacuum-assisted closure has been applied by many clinicians to chronic wounds in humans; however it cannot be used as a replacement for surgical debridement. The initial treatment for every contaminated wound should be the necrosectomy. The VAC therapy has a complementary function and the range of its indications includes pressure sores, stasis ulcers, chronic wounds such as diabetic foot ulcers, post traumatic and post operative wounds, infected wounds such as necrotizing fasciitis or sternal wounds, soft-tissue injuries, bone exposed injuries, abdominal open wounds and for securing a skin graft. We describe our experience with the VAC dressing used to manage acute and chronic wounds in a series of 135 patients, with excellent results together with satisfaction of the patients. PMID:23095568

  2. Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

    SciTech Connect

    Aburto, Andrés; Barría, Agustín; Cárdenas, Areli; Carpio, Daniel; Figueroa, Carlos D.; Burgos, Maria E.; Ardiles, Leopoldo

    2014-10-15

    Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. - Highlights: • Mechanisms of cisplatin-induced-renal damage have not been completely clarified. • Cisplatin induces oxidative stress and apoptosis. • The renal kallikrein-kinin system is protective in experimental acute renal damage. • Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin. • Protection of the kallikrein-kinin system may reduce cisplatin toxicity.

  3. Acute porphyric disorders.

    PubMed

    Moore, A W; Coke, J M

    2000-09-01

    Acute porphyrias are classified into 3 distinct groups of rare genetic disorders of metabolic enzyme biosynthesis. Acute porphyrias can significantly impact multiple organ systems, which often provides a challenge to the dentist presented with such a patient. A case of hereditary coproporphyria is reported in a patient with many of the classical signs and symptoms. The patient also had complex dental needs that required special medical and pharmacotherapeutic modifications. The acute porphyrias are reviewed by the authors with presentation of this challenging case. Recommendations for other dental health care professionals encountering these patients are then presented. PMID:10982942

  4. Acute nephritic syndrome

    MedlinePlus

    Glomerulonephritis - acute; Acute glomerulonephritis; Nephritis syndrome - acute ... Acute nephritic syndrome is often caused by an immune response triggered by an infection or other disease. Common causes ...

  5. Monitoring the impact of the DRG payment system on nursing service context factors in Swiss acute care hospitals: Study protocol

    PubMed Central

    Spirig, Rebecca; Spichiger, Elisabeth; Martin, Jacqueline S.; Frei, Irena Anna; Müller, Marianne; Kleinknecht, Michael

    2014-01-01

    Aims: With this study protocol, a research program is introduced. Its overall aim is to prepare the instruments and to conduct the first monitoring of nursing service context factors at three university and two cantonal hospitals in Switzerland prior to the introduction of the reimbursement system based on Diagnosis Related Groups (DRG) and to further develop a theoretical model as well as a methodology for future monitoring following the introduction of DRGs. Background: DRG was introduced to all acute care hospitals in Switzerland in 2012. In other countries, DRG introduction led to rationing and subsequently to a reduction in nursing care. As result, nursing-sensitive patient outcomes were seriously jeopardised. Switzerland has the opportunity to learn from the consequences experienced by other countries when they introduced DRGs. Their experiences highlight that DRGs influence nursing service context factors such as complexity of nursing care or leadership, which in turn influence nursing-sensitive patient outcomes. For this reason, the monitoring of nursing service context factors needs to be an integral part of the introduction of DRGs. However, most acute care hospitals in Switzerland do not monitor nursing service context data. Nursing managers and hospital executive boards will be in need of this data in the future, in order to distribute resources effectively. Methods/Design: A mixed methods design in the form of a sequential explanatory strategy was chosen. During the preparation phase, starting in spring 2011, instruments were selected and prepared, and the access to patient and nursing data in the hospitals was organized. Following this, online collection of quantitative data was conducted in fall 2011. In summer 2012, qualitative data was gathered using focus group interviews, which helped to describe the processes in more detail. During 2013 and 2014, an integration process is being conducted involving complementing, comparing and contrasting

  6. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

    PubMed Central

    2010-01-01

    Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL). However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo. PMID:20406497

  7. Mapping Acute Systemic Effects of Inhaled Particulate Matter and Ozone: Multiorgan Gene Expression and Glucocorticoid Activity

    PubMed Central

    Thomson, Errol M.; Vladisavljevic, Djordje; Mohottalage, Susantha; Kumarathasan, Prem; Vincent, Renaud

    2013-01-01

    Recent epidemiological studies have demonstrated associations between air pollution and adverse effects that extend beyond respiratory and cardiovascular disease, including low birth weight, appendicitis, stroke, and neurological/neurobehavioural outcomes (e.g., neurodegenerative disease, cognitive decline, depression, and suicide). To gain insight into mechanisms underlying such effects, we mapped gene profiles in the lungs, heart, liver, kidney, spleen, cerebral hemisphere, and pituitary of male Fischer-344 rats immediately and 24h after a 4-h exposure by inhalation to particulate matter (0, 5, and 50mg/m3 EHC-93 urban particles) and ozone (0, 0.4, and 0.8 ppm). Pollutant exposure provoked differential expression of genes involved in a number of pathways, including antioxidant response, xenobiotic metabolism, inflammatory signalling, and endothelial dysfunction. The mRNA profiles, while exhibiting some interorgan and pollutant-specific differences, were remarkably similar across organs for a set of genes, including increased expression of redox/glucocorticoid-sensitive genes and decreased expression of inflammatory genes, suggesting a possible hormonal effect. Pollutant exposure increased plasma levels of adrenocorticotropic hormone and the glucocorticoid corticosterone, confirming activation of the hypothalamic-pituitary-adrenal axis, and there was a corresponding increase in markers of glucocorticoid activity. Although effects were transient and presumably represent an adaptive response to acute exposure in these healthy animals, chronic activation and inappropriate regulation of the hypothalamic-pituitary-adrenal axis are associated with adverse neurobehavioral, metabolic, immune, developmental, and cardiovascular effects. The experimental data are consistent with epidemiological associations of air pollutants with extrapulmonary health outcomes and suggest a mechanism through which such health effects may be induced. PMID:23805001

  8. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects Are Diminished in Adrenalectomized Rats.

    PubMed

    Miller, Desinia B; Snow, Samantha J; Schladweiler, Mette C; Richards, Judy E; Ghio, Andrew J; Ledbetter, Allen D; Kodavanti, Urmila P

    2016-04-01

    Acute ozone exposure increases circulating stress hormones and induces metabolic alterations in animals. We hypothesized that the increase of adrenal-derived stress hormones is necessary for both ozone-induced metabolic effects and lung injury. Male Wistar-Kyoto rats underwent bilateral adrenal demedullation (DEMED), total bilateral adrenalectomy (ADREX), or sham surgery (SHAM). After a 4 day recovery, rats were exposed to air or ozone (1 ppm), 4 h/day for 1 or 2 days and responses assessed immediately postexposure. Circulating adrenaline levels dropped to nearly zero in DEMED and ADREX rats relative to SHAM. Corticosterone tended to be low in DEMED rats and dropped to nearly zero in ADREX rats. Adrenalectomy in air-exposed rats caused modest changes in metabolites and lung toxicity parameters. Ozone-induced hyperglycemia and glucose intolerance were markedly attenuated in DEMED rats with nearly complete reversal in ADREX rats. Ozone increased circulating epinephrine and corticosterone in SHAM but not in DEMED or ADREX rats. Free fatty acids (P = .15) and branched-chain amino acids increased after ozone exposure in SHAM but not in DEMED or ADREX rats. Lung minute volume was not affected by surgery or ozone but ozone-induced labored breathing was less pronounced in ADREX rats. Ozone-induced increases in lung protein leakage and neutrophilic inflammation were markedly reduced in DEMED and ADREX rats (ADREX > DEMED). Ozone-mediated decreases in circulating white blood cells in SHAM were not observed in DEMED and ADREX rats. We demonstrate that ozone-induced peripheral metabolic effects and lung injury/inflammation are mediated through adrenal-derived stress hormones likely via the activation of stress response pathway. PMID:26732886

  9. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    PubMed

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (P<0.05) and IL-8 (P<0.01) responses to T-cell activation. Hierarchical clustering revealed 2 distinct inflammatory clusters associated with previous preeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. PMID:26711734

  10. Detection of acute nervous system injury with advanced diffusion-weighted MRI: a simulation and sensitivity analysis.

    PubMed

    Skinner, Nathan P; Kurpad, Shekar N; Schmit, Brian D; Budde, Matthew D

    2015-11-01

    Diffusion-weighted imaging (DWI) is a powerful tool to investigate the microscopic structure of the central nervous system (CNS). Diffusion tensor imaging (DTI), a common model of the DWI signal, has a demonstrated sensitivity to detect microscopic changes as a result of injury or disease. However, DTI and other similar models have inherent limitations that reduce their specificity for certain pathological features, particularly in tissues with complex fiber arrangements. Methods such as double pulsed field gradient (dPFG) and q-vector magic angle spinning (qMAS) have been proposed to specifically probe the underlying microscopic anisotropy without interference from the macroscopic tissue organization. This is particularly important for the study of acute injury, where abrupt changes in the microscopic morphology of axons and dendrites manifest as focal enlargements known as beading. The purpose of this work was to assess the relative sensitivity of DWI measures to beading in the context of macroscopic fiber organization and edema. Computational simulations of DWI experiments in normal and beaded axons demonstrated that, although DWI models can be highly specific for the simulated pathologies of beading and volume fraction changes in coherent fiber pathways, their sensitivity to a single idealized pathology is considerably reduced in crossing and dispersed fibers. However, dPFG and qMAS have a high sensitivity for beading, even in complex fiber tracts. Moreover, in tissues with coherent arrangements, such as the spinal cord or nerve fibers in which tract orientation is known a priori, a specific dPFG sequence variant decreases the effects of edema and improves specificity for beading. Collectively, the simulation results demonstrate that advanced DWI methods, particularly those which sample diffusion along multiple directions within a single acquisition, have improved sensitivity to acute axonal injury over conventional DTI metrics and hold promise for more

  11. Protective Effects of Zinc Against Acute Arsenic Toxicity by Regulating Antioxidant Defense System and Cumulative Metallothionein Expression.

    PubMed

    Ganger, Renuka; Garla, Roobee; Mohanty, Biraja Prasad; Bansal, Mohinder Pal; Garg, Mohan Lal

    2016-02-01

    Arsenic (As), a toxic metalloid, is one of the major global concerns. The toxicity resulting from As exposure is linked to the generation of reactive oxygen intermediates during their redox cycling and metabolic activation processes that cause lipid peroxidation (LPO). Zinc (Zn), a redox-inactive metal, helps to maintain cellular functions because of its prominent role in antioxidant network through multiple mechanisms. The present study, therefore, explores the effectiveness of administered Zn to combat against acute As toxicity by analysis of antioxidant defense status, alkaline phosphatase (ALP) activity, histological profile, MT expression, and elemental status in rat liver. To achieve this goal, four experimental groups, one control and three receiving different metal supplementations, were chosen (group 1, control; group 2, Zn supplemented; group 3, As substituted; group 4, Zn + As supplemented). The levels of reduced glutathione (GSH) and activities of glutathione reductase (GR) and ALP were lowered, whereas LPO levels and activity of superoxide dismutase (SOD) were elevated with no significant change in catalase (CAT) activity. Histopathological changes were also observed in the As substituted group in comparison to the control. Particle-induced X-ray emission (PIXE) analysis showed decrease in Fe and S concentration in rat liver after As intoxication, whereas As was below detection limit, i.e., <1 ppm. Zn administration almost restored the antioxidants, ALP activity, histopathological changes, and elemental status. A cumulative increase in MT expression was found with the combined treatment of Zn and As. Also, Zn alone caused no significant change in the antioxidant defense system. It can be concluded that restoration of antioxidant activity and increased MT expression are the two independent protective mechanisms of Zn to reduce acute As toxicity. PMID:26113309

  12. Acute hazardous substance releases resulting in adverse health consequences in children: Hazardous Substances Emergency Events Surveillance system, 1996-2003.

    PubMed

    Wattigney, Wendy A; Kaye, Wendy E; Orr, Maureen F

    2007-11-01

    Because of their small size and ongoing organ development, children may be more susceptible than adults to the harmful effects of toxic chemicals. The objective of the study reported here was to identify frequent locations, released substances, and factors contributing to short-term chemical exposures associated with adverse health consequences experienced by children. The study examined the Hazardous Substances Emergency Events Surveillance (HSEES) system data from 1996-2003. Eligible events involved the acute release of a hazardous substance associated with at least one child being injured. The study found that injured children were predominantly at school, home, or a recreational center when events took place. School-related events were associated with the accidental release of acids and the release of pepper spray by pranksters. Carbon monoxide poisonings occurring in the home, retail stores, entertainment facilities, and hotels were responsible for about 10 percent of events involving child victims. Chlorine was one of the top chemicals harmful to children, particularly at public swimming pools. Although human error contributed to the majority of releases involving child victims, equipment failure was responsible for most chlorine and ammonia releases. The authors conclude that chemical releases resulting in injury to children occur mostly in schools, homes, and recreational areas. Surveillance of acute hazardous chemical releases helped identify contributing causes and can guide the development of prevention outreach activities. Chemical accidents cannot be entirely prevented, but efforts can be taken to provide safer environments in which children can live, learn, and play. Wide dissemination of safety recommendations and education programs is required to protect children from needless environmental dangers. PMID:18044249

  13. Proteolytic systems and AMP-activated protein kinase are critical targets of acute myeloid leukemia therapeutic approaches

    PubMed Central

    Pereira, Olga; Sampaio-Marques, Belém; Paiva, Artur; Correia-Neves, Margarida; Castro, Isabel; Ludovico, Paula

    2015-01-01

    The therapeutic strategies against acute myeloid leukemia (AML) have hardly been modified over four decades. Although resulting in a favorable outcome in young patients, older individuals, the most affected population, do not respond adequately to therapy. Intriguingly, the mechanisms responsible for AML cells chemoresistance/susceptibility are still elusive. Mounting evidence has shed light on the relevance of proteolytic systems (autophagy and ubiquitin-proteasome system, UPS), as well as the AMPK pathway, in AML biology and treatment, but their exact role is still controversial. Herein, two AML cell lines (HL-60 and KG-1) were exposed to conventional chemotherapeutic agents (cytarabine and/or doxorubicin) to assess the relevance of autophagy and UPS on AML cells’ response to antileukemia drugs. Our results clearly showed that the antileukemia agents target both proteolytic systems and the AMPK pathway. Doxorubicin enhanced UPS activity while drugs’ combination blocked autophagy specifically on HL-60 cells. In contrast, KG-1 cells responded in a more subtle manner to the drugs tested consistent with the higher UPS activity of these cells. In addition, the data demonstrates that autophagy may play a protective role depending on AML subtype. Specific modulators of autophagy and UPS are, therefore, promising targets for combining with standard therapeutic interventions in some AML subtypes. PMID:25537507

  14. Applications for detection of acute kidney injury using electronic medical records and clinical information systems: workgroup statements from the 15(th) ADQI Consensus Conference.

    PubMed

    James, Matthew T; Hobson, Charles E; Darmon, Michael; Mohan, Sumit; Hudson, Darren; Goldstein, Stuart L; Ronco, Claudio; Kellum, John A; Bagshaw, Sean M

    2016-01-01

    Electronic medical records and clinical information systems are increasingly used in hospitals and can be leveraged to improve recognition and care for acute kidney injury. This Acute Dialysis Quality Initiative (ADQI) workgroup was convened to develop consensus around principles for the design of automated AKI detection systems to produce real-time AKI alerts using electronic systems. AKI alerts were recognized by the workgroup as an opportunity to prompt earlier clinical evaluation, further testing and ultimately intervention, rather than as a diagnostic label. Workgroup members agreed with designing AKI alert systems to align with the existing KDIGO classification system, but recommended future work to further refine the appropriateness of AKI alerts and to link these alerts to actionable recommendations for AKI care. The consensus statements developed in this review can be used as a roadmap for development of future electronic applications for automated detection and reporting of AKI. PMID:26925245

  15. Systemic combined melatonin-mitochondria treatment improves acute respiratory distress syndrome in the rat.

    PubMed

    Sun, Cheuk-Kwan; Lee, Fan-Yen; Kao, Ying-Hsien; Chiang, Hsin-Ju; Sung, Pei-Hsun; Tsai, Tzu-Hsien; Lin, Yu-Chun; Leu, Steve; Wu, Ying-Chung; Lu, Hung-I; Chen, Yung-Lung; Chung, Sheng-Ying; Su, Hong-Lin; Yip, Hon-Kan

    2015-03-01

    Despite high in-hospital mortality associated with acute respiratory distress syndrome (ARDS), there is no effective therapeutic strategy. We tested the hypothesis that combined melatonin-mitochondria treatment ameliorates 100% oxygen-induced ARDS in rats. Adult male Sprague-Dawley rats (n = 40) were equally categorized into normal controls, ARDS, ARDS-melatonin, ARDS with intravenous liver-derived mitochondria (1500 μg per rat 6 hr after ARDS induction), and ARDS receiving combined melatonin-mitochondria. The results showed that 22 hr after ARDS induction, oxygen saturation (saO2 ) was lowest in the ARDS group and highest in normal controls, significantly lower in ARDS-melatonin and ARDS-mitochondria than in combined melatonin-mitochondria group, and significantly lower in ARDS-mitochondria than in ARDS-melatonin group. Conversely, right ventricular systolic blood pressure and lung weight showed an opposite pattern compared with saO2 among all groups (all P < 0.001). Histological integrity of alveolar sacs showed a pattern identical to saO2 , whereas lung crowding score exhibited an opposite pattern (all P < 0.001). Albumin level and inflammatory cells (MPO+, CD40+, CD11b/c+) from bronchoalveolar lavage fluid showed a pattern opposite to saO2 (all P < 0.001). Protein expression of indices of inflammation (MMP-9, TNF-α, NF-κB), oxidative stress (oxidized protein, NO-1, NOX-2, NOX-4), apoptosis (mitochondrial Bax, cleaved caspase-3, and PARP), fibrosis (Smad3, TGF-β), mitochondrial damage (cytochrome C), and DNA damage (γ-H2AX+) exhibited an opposite pattern compared to saO2 in all groups, whereas protein (HO-1, NQO-1, GR, GPx) and cellular (HO-1+) expressions of antioxidants exhibited a progressively increased pattern from normal controls to ARDS combined melatonin-mitochondria group (all P < 0.001). In conclusion, combined melatonin-mitochondrial was superior to either treatment alone in attenuating ARDS in this rat model. PMID:25491480

  16. Systemic acute phase proteins response in calves experimentally infected with Eimeria zuernii.

    PubMed

    Lassen, Brian; Bangoura, Berit; Lepik, Triin; Orro, Toomas

    2015-09-15

    Acute phase proteins (APPs) have been demonstrated to be useful in evaluating general health stress and diseases in cattle. Serum amyloid A (SAA) and haptoglobin (Hp) are APPs that are produced during inflammation, and likely play a role in host immunological defence against Eimeria infection and the associated intestinal tissue damage. We investigated the involvement of SAA and HP in an experimental study, including three groups of calves: a control group (group 0, n=11), and two groups infected with either 150,000 or 250,000 Eimeria zuernii oocysts (group 1 (n=11) and group 2 (n=12), respectively). The calves were monitored for 28 days and data was collected on oocyst excretion, faecal score, animal weight, and SAA and Hp serum concentrations. Generalized linear mixed models showed that the clinical symptoms, indicated by an increase in the number of oocysts in the faeces and severe diarrhoea, manifested at patency for group 1 and 2. Serum Hp and SAA levels also increased during this period. Hp appeared to be a more sensitive marker than SAA, and differences between groups 1 and 2 were observed only for Hp. Linear regression models showed a negative association between weight gain and Hp concentrations, calculated as the area under the curve (AUC) during the overall experimental period and the patency period. A similar result was seen for SAA only during the patency period. This result supports the assumption that reduced weight gain due to E. zuernii infection is an immunologically driven process that involves an increase in APPs. A random intercept regression model of oocyst shedding groups showed that calves shedding 1-500 oocysts had reduced concentrations of Hp, indicating that a different immunological reaction occurs during mild shedding of E. zuernii oocysts than during more intensive shedding. A similar model was used to examine associations between faecal scores and Hp concentrations for each group. Group 2 calves with haemorrhagic diarrhoea displayed

  17. Effect of acute lithium administration on penile erection: involvement of nitric oxide system

    PubMed Central

    Sandoughdaran, Saleh; Sadeghipour, Hamed; Sadeghipour, Hamid Reza

    2016-01-01

    lithium, (p<0.001). Conclusion: These results suggest acute treatments with lithium cause erectile dysfunction in an in-vivo rat model. Furthermore it seems that the NO pathway might play role in erectile dysfunction associated with lithium treatment. Findings also suggest that Sildenafil may be effective in treatment of lithium-associated erectile dysfunction. PMID:27200425

  18. Acute viral infections in patients with systemic lupus erythematosus: description of 23 cases and review of the literature.

    PubMed

    Ramos-Casals, Manuel; Cuadrado, María José; Alba, Paula; Sanna, Giovanni; Brito-Zerón, Pilar; Bertolaccini, Laura; Babini, Alejandra; Moreno, Asunción; D'Cruz, David; Khamashta, Munther A

    2008-11-01

    Few studies have evaluated the impact of viral infections on the daily management of patients with systemic lupus erythematosus (SLE). We analyzed the etiology and clinical features of acute viral infections arising in patients with SLE and their influence on the diagnosis, prognosis, and treatment of SLE. Cases occurring within the last 5 years were selected from the databases of 3 large teaching hospitals. Acute viral infections were confirmed by the identification of specific antiviral IgM antibodies and subsequent seroconversion with detection of specific IgG antibodies. In autopsy studies, macroscopic findings suggestive of viral infection were confirmed by direct identification of the virus or viruses in tissue samples. We performed a MEDLINE search for additional cases reported between January 1985 and March 2008. We included 88 cases (23 from our clinics and 65 from the literature review) of acute viral infections in patients with SLE. Twenty-five patients were diagnosed with new-onset SLE (fulfillment of the 1997 SLE criteria) associated with infection by human parvovirus B19 (n = 15), cytomegalovirus (CMV; n = 6), Epstein-Barr virus (EBV; n = 3), and hepatitis A virus (n = 1). The remaining 63 cases of acute viral infections arose in patients already diagnosed with SLE: in 18 patients, symptoms related to infection mimicked a lupus flare, 36 patients, including 1 patient from the former group who presented with both conditions, presented organ-specific viral infections (mainly pneumonitis, colitis, retinitis, and hepatitis), and 10 patients presented a severe, multiorgan process similar to that described in catastrophic antiphospholipid syndrome-the final diagnosis was hemophagocytic syndrome in 5 cases and disseminated viral infection in 5. Twelve patients died due to infection caused by CMV (n = 5), herpes simplex virus (n = 4), EBV (n = 2), and varicella zoster virus (n = 1). Autopsies were performed in 9 patients and disclosed disseminated herpetic

  19. Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A®) Following Acute Repeated Inhalation Exposure

    PubMed Central

    Roberts, Jenny R; Anderson, Stacey E; Kan, Hong; Krajnak, Kristine; Thompson, Janet A; Kenyon, Allison; Goldsmith, William T; McKinney, Walter; Frazer, David G; Jackson, Mark; Fedan, Jeffrey S

    2014-01-01

    INTRODUCTION Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. METHODS The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m3, five hours per day, over nine work days, or filtered air (control). At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. RESULTS No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following methacholine (MCh) inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM) to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP) responses to these agents; however, the baseline heart rate (HR) and HR responses to isoproterenol (ISO) were significantly elevated at one-day post exposure, with resolution

  20. Innovative delivery systems for migraine: the clinical utility of a transdermal patch for the acute treatment of migraine.

    PubMed

    Rapoport, Alan M; Freitag, Fred; Pearlman, Starr H

    2010-11-01

    Migraine is a disabling, painful primary headache disorder that is associated with various combinations of neurological, gastrointestinal, autonomic and pain symptoms. Gastrointestinal disturbances associated with migraine, including nausea and vomiting, affect a majority of migraineurs and often result in a delay in taking or avoidance of pharmacological intervention. Gastric stasis and vomiting may lead to delayed or inconsistent absorption of orally administered medications. Many migraineurs awake early in the morning with their attack progressing and already associated with nausea and vomiting. As a result, there is a need for a novel, non-invasive, non-oral delivery system for fast and effective acute treatment of migraine. There are two non-oral delivery systems currently available in the US for the acute treatment of migraine: three nasal sprays and two injectable formulations. Although nasal sprays depend partially on nasal mucosal absorption, a significant amount of drug is swallowed, transits the stomach and is absorbed in the small intestine, which is not as rapid or effective a route of delivery for those migraineurs with gastric stasis. Sumatriptan is rapidly absorbed by subcutaneous injection with or without a needle, but the invasiveness and discomfort of the delivery, the high incidence of adverse events and the high recurrence rate all limit its use for many patients. Iontophoretic delivery of medication is a non-invasive transdermal approach that uses small amounts of electrical current to promote rapid movement of the ionized drug through the skin and into the systemic circulation. This delivery bypasses hepatic first-pass metabolism and also avoids gastric transit delay and slowing of small intestinal absorption associated with gastrointestinal stasis in migraineurs. Two pharmacokinetic studies have demonstrated that iontophoretic transdermal delivery of sumatriptan results in rapid and consistent achievement of therapeutic plasma concentrations

  1. Acute sacroiliitis.

    PubMed

    Slobodin, Gleb; Rimar, Doron; Boulman, Nina; Kaly, Lisa; Rozenbaum, Michael; Rosner, Itzhak; Odeh, Majed

    2016-04-01

    The purpose of this study was to review the data on the etiology, risk factors, clinical presentations, and diagnosis of acute sacroiliitis. A Pubmed search utilizing the indexing term "acute sacroiliitis" was conducted and the data pertinent to the aim of the review was extracted and organized in accordance with the preplanned structure of the manuscript. The diagnosis of acute sacroiliitis is often challenging because of both the relative rarity of this presentation and diverse character of acute sacroiliac pain, frequently mimicking other, more prevalent disorders. Technetium bone scintigraphy can localize the disease process to the sacroiliac joint, while computed tomography or magnetic resonance imaging can be used for the detailed characterization and the extent of the disease as well as the diagnosis of complications. Pyogenic sacroiliitis is by far the most common cause of acute sacroiliitis. Brucellosis, acute sacroiliitis in the course of reactive arthritis, and crystalline-induced sacroiliitis frequently imitate pyogenic sacroiliitis. Acute sacroiliitis can rarely be also related to hematological malignancies or treatment with isotretinoin. Awareness to the possibility of acute sacroiliitis and a thorough physical examination are the necessary prerequisites to its timely diagnosis, while the appropriate laboratory and imaging studies should confirm the precise diagnosis and direct the appropriate treatment strategy. PMID:26847855

  2. SYSTEMIC IMBALANCE OF ESSENTIAL METALS AND CARDIAC GENE EXPRESSION IN RATS FOLLOWING ACUTE PULMONARY ZINC EXPOSURE

    EPA Science Inventory

    We have recently demonstrated that PM containing water-soluble zinc may cause cardiac injury following pulmonary exposure. To investigate if pulmonary zinc exposure causes systemic metal imbalance and direct cardiac effects, we intratracheally (IT) instilled male Wistar Kyoto (WK...

  3. Proton pump inhibitors protect mice from acute systemic inflammation and induce long-term cross-tolerance

    PubMed Central

    Balza, E; Piccioli, P; Carta, S; Lavieri, R; Gattorno, M; Semino, C; Castellani, P; Rubartelli, A

    2016-01-01

    Incidence of sepsis is increasing, representing a tremendous burden for health-care systems. Death in acute sepsis is attributed to hyperinflammatory responses, but the underlying mechanisms are still unclear. We report here that proton pump inhibitors (PPIs), which block gastric acid secretion, selectively inhibited tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion by Toll-like receptor (TLR)-activated human monocytes in vitro, in the absence of toxic effects. Remarkably, the oversecretion of IL-1β that represents a hallmark of monocytes from patients affected by cryopyrin-associated periodic syndrome is also blocked. Based on these propaedeutic experiments, we tested the effects of high doses of PPIs in vivo in the mouse model of endotoxic shock. Our data show that a single administration of PPI protected mice from death (60% survival versus 5% of untreated mice) and decreased TNF-α and IL-1β systemic production. PPIs were efficacious even when administered after lipopolysaccharide (LPS) injection. PPI-treated mice that survived developed a long-term cross-tolerance, becoming resistant to LPS- and zymosan-induced sepsis. In vitro, their macrophages displayed impaired TNF-α and IL-1β to different TLR ligands. PPIs also prevented sodium thioglycollate-induced peritoneal inflammation, indicating their efficacy also in a non-infectious setting independent of TLR stimulation. Lack of toxicity and therapeutic effectiveness make PPIs promising new drugs against sepsis and other severe inflammatory conditions. PMID:27441656

  4. Association between Floods and Acute Cardiovascular Diseases: A Population-Based Cohort Study Using a Geographic Information System Approach

    PubMed Central

    Vanasse, Alain; Cohen, Alan; Courteau, Josiane; Bergeron, Patrick; Dault, Roxanne; Gosselin, Pierre; Blais, Claudia; Bélanger, Diane; Rochette, Louis; Chebana, Fateh

    2016-01-01

    Background: Floods represent a serious threat to human health beyond the immediate risk of drowning. There is few data on the potential link between floods and direct consequences on health such as on cardiovascular health. This study aimed to explore the impact of one of the worst floods in the history of Quebec, Canada on acute cardiovascular diseases (CVD). Methods: A cohort study with a time series design with multiple control groups was built with the adult population identified in the Quebec Integrated Chronic Disease Surveillance System. A geographic information system approach was used to define the study areas. Logistic regressions were performed to compare the occurrence of CVD between groups. Results: The results showed a 25%–27% increase in the odds in the flooded population in spring 2011 when compared with the population in the same area in springs 2010 and 2012. Besides, an increase up to 69% was observed in individuals with a medical history of CVD. Conclusion: Despite interesting results, the association was not statistically significant. A possible explanation to this result can be that the population affected by the flood was probably too small to provide the statistical power to answer the question, and leaves open a substantial possibility for a real and large effect. PMID:26828511

  5. Acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis in the dog.

    PubMed Central

    Anderson, W P; Johnston, C I; Korner, P I

    1979-01-01

    1. The acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. 2. Stenosis was induced over 30 sec by inflation of a cuff around the renal artery to lower distal pressure to 60, 40 or 20 mmHg, with stenosis maintained for 1 hr. This resulted in an immediate fall in renal vascular resistance, but over the next 5--30 min both resistance and renal artery pressure were restored back towards prestenosis values. Only transient increases in systemic arterial blood pressure and plasma renin and angiotensin levels were seen with the two milder stenoses. Despite restoration of renal artery pressure, renal blood flow remained reduced at all grades of stenosis. 3. Pre-treatment with angiotensin I converting enzyme inhibitor or sarosine1, isoleucone8 angiotensin II greatly attenuated or abolished the restoration of renal artery pressure and renal vascular resistance after stenosis, and plasma renin and angiotensin II levels remained high. Renal dilatation was indefinitely maintained, but the normal restoration of resistance and pressure could be simulated by infusing angiotensin II into the renal artery. 4. The effective resistance to blood flow by the stenosis did not remain constant but varied with changes in the renal vascular resistance. PMID:219182

  6. Immediate and long-term posttherapy neuropsychologic performance in children with acute lymphoblastic leukemia treated without central nervous system radiation.

    PubMed

    Tamaroff, M; Miller, D R; Murphy, M L; Salwen, R; Ghavimi, F; Nir, Y

    1982-10-01

    Intellectual and neuropsychologic test performance was studied in 41 children with acute lymphoblastic leukemia within one year of completing multidrug therapy in which intrathecal methotrexate was the sole agent of central nervous system prophylaxis. To control for possible effects of intensive systemic chemotherapy and the disruptive psychosocial effects of treatment on psychometric test function, 33 children with embryonal rhabdomyosarcoma who had no CNS disease or treatment were similarly studied. All patients studied had been in continuous complete remission since diagnosis. Within each diagnostic group, patients were placed in a younger (less than 8 years) or an older (more than 8 years) group depending on age at the time of testing. No significant difference was found in intellectual function between the young ALL and ERMS groups or between the total ALL and ERMS groups. Further five-year follow-up of 12 of the youngest ALL patients showed no significant long-term change in intellectual or other specific neuropsychologic functions. Children with ALL who remained in continuous complete remission from diagnosis and who were treated with prophylactic intrathecal methotrexate and no CNS radiation did not have global or specific neuropsychologic impairment. PMID:6956704

  7. Proton pump inhibitors protect mice from acute systemic inflammation and induce long-term cross-tolerance.

    PubMed

    Balza, E; Piccioli, P; Carta, S; Lavieri, R; Gattorno, M; Semino, C; Castellani, P; Rubartelli, A

    2016-01-01

    Incidence of sepsis is increasing, representing a tremendous burden for health-care systems. Death in acute sepsis is attributed to hyperinflammatory responses, but the underlying mechanisms are still unclear. We report here that proton pump inhibitors (PPIs), which block gastric acid secretion, selectively inhibited tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion by Toll-like receptor (TLR)-activated human monocytes in vitro, in the absence of toxic effects. Remarkably, the oversecretion of IL-1β that represents a hallmark of monocytes from patients affected by cryopyrin-associated periodic syndrome is also blocked. Based on these propaedeutic experiments, we tested the effects of high doses of PPIs in vivo in the mouse model of endotoxic shock. Our data show that a single administration of PPI protected mice from death (60% survival versus 5% of untreated mice) and decreased TNF-α and IL-1β systemic production. PPIs were efficacious even when administered after lipopolysaccharide (LPS) injection. PPI-treated mice that survived developed a long-term cross-tolerance, becoming resistant to LPS- and zymosan-induced sepsis. In vitro, their macrophages displayed impaired TNF-α and IL-1β to different TLR ligands. PPIs also prevented sodium thioglycollate-induced peritoneal inflammation, indicating their efficacy also in a non-infectious setting independent of TLR stimulation. Lack of toxicity and therapeutic effectiveness make PPIs promising new drugs against sepsis and other severe inflammatory conditions. PMID:27441656

  8. Porous nanoparticles as delivery system of complex antigens for an effective vaccine against acute and chronic Toxoplasma gondii infection.

    PubMed

    Dimier-Poisson, Isabelle; Carpentier, Rodolphe; N'Guyen, Thi Thanh Loi; Dahmani, Fatima; Ducournau, Céline; Betbeder, Didier

    2015-05-01

    Development of sub-unit mucosal vaccines requires the use of specific delivery systems or immune-modulators such as adjuvants to improve antigen immunogenicity. Nasal route for vaccine delivery by nanoparticles has attracted much interest but mechanisms triggering effective mucosal and systemic immune response are still poorly understood. Here we study the loading of porous nanoparticles (DGNP) with a total extract of Toxoplasma gondii antigens (TE), the delivery of TE by DGNP into airway epithelial, macrophage and dendritic cells, and the subsequent cellular activation. In vitro, DGNP are able to load complex antigens in a stable and quantitative manner. The outstanding amount of antigen association by DGNP is used to deliver TE in airway mucosa cells to induce a cellular maturation with an increased secretion of pro-inflammatory cytokines. Evaluation of nasal vaccine efficiency is performed in vivo on acute and chronic toxoplasmosis mouse models. A specific Th1/Th17 response is observed in vivo after vaccination with DGNP/TE. This is associated with high protection against toxoplasmosis regarding survival and parasite burden, correlated with an increased delivery of antigens by DGNP in airway mucosa cells. This study provides evidence of the potential of DGNP for the development of new vaccines against a range of pathogens. PMID:25736506

  9. Evaluation of the Acute Flacid Paralysis (AFP) Surveillance System in Bikita District Masvingo Province 2010

    PubMed Central

    2014-01-01

    Background AFP is a rare syndrome and serves as a proxy for poliomyelitis. The main objective of AFP surveillance is to detect circulating wild polio virus and provide data for developing effective prevention and control strategies as well planning and decision making. Bikita district failed to detect a case for the past two years. Findings A total of 31 health workers from 14 health centres were interviewed. Health worker knowledge on AFP was low in Bikita. The system was acceptable, flexible, and representative but not stable and not sensitive since it missed1 AFP case. The system was not useful to the district since data collected was not locally used in anyway. The cost of running the system was high. The district had no adequate resources to run the system. Reasons for not reporting cases was that the mothers were not bringing children with AFP and ignorance of health workers on syndromes captured under AFP. Conclusion Health worker’s knowledge on AFP was low and all interviewed workers needed training surveillance. The system was found to be flexible but unacceptable. Reasons for failure to detect AFP cases could be, no cases reporting to the centres, lack of knowledge on health workers hence failure to recognise symptoms, high staff turnover. PMID:24742014

  10. Estimating the number of cases of acute gastrointestinal illness (AGI) associated with Canadian municipal drinking water systems.

    PubMed

    Murphy, H M; Thomas, M K; Medeiros, D T; McFADYEN, S; Pintar, K D M

    2016-05-01

    The estimated burden of endemic acute gastrointestinal illness (AGI) annually in Canada is 20·5 million cases. Approximately 4 million of these cases are domestically acquired and foodborne, yet the proportion of waterborne cases is unknown. A number of randomized controlled trials have been completed to estimate the influence of tap water from municipal drinking water plants on the burden of AGI. In Canada, 83% of the population (28 521 761 people) consumes tap water from municipal drinking water plants serving >1000 people. The drinking water-related AGI burden associated with the consumption of water from these systems in Canada is unknown. The objective of this research was to estimate the number of AGI cases attributable to consumption of drinking water from large municipal water supplies in Canada, using data from four household drinking water intervention trials. Canadian municipal water treatment systems were ranked into four categories based on source water type and quality, population size served, and treatment capability and barriers. The water treatment plants studied in the four household drinking water intervention trials were also ranked according to the aforementioned criteria, and the Canadian treatment plants were then scored against these criteria to develop four AGI risk groups. The proportion of illnesses attributed to distribution system events vs. source water quality/treatment failures was also estimated, to inform the focus of future intervention efforts. It is estimated that 334 966 cases (90% probability interval 183 006-501 026) of AGI per year are associated with the consumption of tap water from municipal systems that serve >1000 people in Canada. This study provides a framework for estimating the burden of waterborne illness at a national level and identifying existing knowledge gaps for future research and surveillance efforts, in Canada and abroad. PMID:26564554