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Sample records for double anti-platelet therapy

  1. Targeting Phosphodiesterases in Anti-platelet Therapy

    PubMed Central

    Rondina, Matthew T.; Weyrich, Andrew S.

    2013-01-01

    There are two primary modes of platelet inhibition: blockade of membrane receptors or neutralization of intracellular pathways. Both means of inhibition have proven benefits in the prevention and resolution of atherothrombotic events. With regard to intracellular inhibition, phosphodiesterases (PDEs) are fundamental for platelet function. Platelets possess several PDEs (PDE2, PDE3 and PDE5) that catalyze the hydrolysis of cyclic adenosine 3′-5′-monophosphate (cAMP) and cyclic guanosine 3′-5′-monophosphate (cGMP), thereby limiting the levels of intracellular nucleotides. PDE inhibitors, such as cilostazol and dipyridamole, dampen platelet function by increasing cAMP and cGMP levels. This review focuses on the roles of PDE inhibitors in modulating platelet function, with particular attention paid to drugs that have anti-platelet clinical indications. PMID:22918733

  2. Anti-platelet therapy in small animal medicine.

    PubMed

    Thomason, J; Lunsford, K; Mackin, A

    2016-08-01

    Thromboembolism is a significant complication in many commonly encountered diseases, and can be a devastating sequel to otherwise treatable conditions. Platelets play an essential role in the hemostatic process and, consequently, are associated with thrombus formation. Platelets adhere to denuded vascular subendothelium, recruit additional platelets and cells, aggregate, and provide the catalytic surface for thrombin production and fibrin formation. Therapy to prevent unwanted thrombus formation and thromboembolic crises is essential in the management of hypercoagulable patients. Unfortunately, many of the medications used in veterinary medicine that inhibit or modulate coagulation factors, such as the heparins, are cost prohibitive, only effective when administered by injection or require frequent drug monitoring, and are therefore poor choices for long term at home therapy. While the role of the platelet in pathologic thrombus formation is not fully understood, veterinarians often resort to anti-platelet therapy in the management of patients at risk for thromboembolic complications, because many anti-platelet medications are inexpensive, require minimal drug monitoring, and can be given orally. The aim of this review is to discuss the anti-platelet therapies that are currently being used or being considered for use to inhibit platelet function and reduce thromboembolic complications in hypercoagulable dogs and cats. PMID:26969126

  3. Pharmacogenomics of Anti-platelet and Anti-coagulation Therapy

    PubMed Central

    Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.

    2013-01-01

    Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323

  4. Anti-platelet therapy and managing ulcer risk.

    PubMed

    Chan, Francis K L

    2012-02-01

    Low-dose aspirin (ASA) has emerged as one of the most important causes of peptic ulcer bleeding in developed countries. Among the risk factors of ASA-associated ulcer bleeding, Helicobacter pylori infection is one of the few that is treatable. Recent evidence showed that among patients with a history of ASA-associated ulcer bleeding, the long-term incidence of recurrent bleeding with ASA use is low after eradication of H. pylori alone. Thus, test-and-treat H. pylori is a potentially useful strategy for ASA users with high ulcer risk. However, the risk of bleeding is further increased by combining other anti-platelet drugs (e.g. clopidogrel) with ASA in acute coronary syndromes and coronary stent placement. There is good evidence that co-therapy with a proton-pump inhibitor (PPI) reduces upper gastrointestinal bleeding with ASA alone or dual anti-platelet therapy. Recently, several meta-analyses of observational studies found that concurrent use of PPI and clopidogrel was associated with increased risk of major adverse cardiovascular events. Overall, the evidence does not suggest a clinically important interaction between PPIs and clopidogrel. However, there is a subset of patients who have reduced conversion of clopidogrel to its active metabolites due to genetic polymorphism of hepatic P-450 (carriers of CYP2C19 loss-of-function alleles). Since PPIs are also metabolized by similar hepatic enzymes, it is uncertain whether patients carrying CY2C19 loss-of-function alleles are susceptible to concomitant PPI use. In the future, management of patients on dual anti-platelet therapy needs to be individualized according to their thrombotic and bleeding risks. PMID:22142030

  5. Spontaneous hematoma in the setting of dual anti-platelet therapy with ticagrelor: A case report

    PubMed Central

    FENG, CHUNGUANG; WANG, LINGUANG; WANG, LULU

    2016-01-01

    A 69-year-old male patient was admitted to hospital because a lump was discovered, accompanied with pain lasting 5 h under his right scapula. Two months earlier, he had undergone a double-stent insertion operation due to lesions on the end of the left main coronary artery, the opening of left circumflex artery, and the opening of the anterior descending branch. After the operation, he was administered with dual anti-platelet therapy (DAPT) with aspirin and ticagrelor and was diagnosed with hematoma under his right scapula through ultrasonic inspection. It was established that no other factor, except DAPT, was responsible for his spontaneous hematoma. PMID:27347115

  6. Anti-platelet therapy and aspirin resistance - clinically and chemically relevant?

    PubMed

    Rafferty, M; Walters, M R; Dawson, J

    2010-01-01

    Platelets play a central role in the pathogenesis of the atherothrombosis which ultimately causes myocardial infarction, stroke and peripheral vascular disease. Commonly used oral anti-platelet drugs include aspirin (an irreversible inhibitor of cyclo-oxygenase), clopidogrel (an ADP receptor antagonist), other thienopyridines such as ticlopidine and prasgruel, and dipyridamole (an inhibitor of adenosine reuptake and platelet phosphodiesterase). Newer agents are in development and one, ticagrelor, a reversible ADP receptor antagonist has shown promise. Despite their proven benefit, recurrent vascular events still occur in those taking anti-platelet drugs. This has led to the concept of anti-platelet resistance, most commonly aspirin resistance as this drug is the cornerstone of most regimens. The causes of aspirin resistance are numerous but potential mechanisms include lack of patient adherence, non COX-1 mediated thromboxane A2 synthesis, increased activity of alternate platelet activation pathways, interference of aspirin action by other drugs and probably pharmacogenetic factors. Measurement of platelet response to aspirin is made possible using a number of in-vitro laboratory assays of platelet function which include measurement of thromboxane A2 metabolites as well as newer point-of-care assays of platelet aggregation. The phenomenon of aspirin resistance is important as it raises the possibility of developing strategies to identify those who respond best to a particular anti-platelet regimen, or to development of newer anti-platelet therapies to which more patients respond. This review discusses important aspects of aspirin resistance both in terms of clinical medicine, alternative anti-platelet strategies, and the potential to overcome its various causes. PMID:21062249

  7. Pharmacogenomics of Anti-platelet Therapy: How much evidence is enough for clinical implementation?

    PubMed Central

    Perry, Christina G.; Shuldiner, Alan R.

    2013-01-01

    Pharmacogenomics, the study of the genomics of drug response and adverse effects, holds great promise for more effective individualized (personalized) medicine. Recent evidence supports a role of loss-of-function variants in the cytochrome P450 enzyme CYP2C19 as a determinant of clopidogrel response. Those who carry loss-of-function variants do not metabolize clopidogrel, a prodrug, into its active form resulting in decreased inhibition of platelet function and a higher likelihood of recurrent cardiovascular events. Despite a large body of evidence supporting clinical utility, adoption of anti-platelet pharmacogenetics into clinical practice has been slow. In this review, we summarize the pharmacokinetic, pharmacodynamics, and clinical evidence, identify gaps in knowledge and other barriers that appear to be slowing adoption, and describe CYP2C19 pharmacogenetics implementation projects currently underway. Only when we surmount these barriers will the astute clinician be able to use pharmacogenetic information in conjunction with the history, physical exam, and other medical tests and information to choose the most efficacious anti-platelet therapy for each individual patient. PMID:23697979

  8. Endothelialization of drug eluting stents and its impact on dual anti-platelet therapy duration.

    PubMed

    Habib, Anwer; Finn, Aloke V

    2015-03-01

    Coronary artery disease is a leading cause of death and disability worldwide with contemporary treatment strategies employing both optimal medical therapy and catheter based percutaneous coronary intervention (PCI) with drug eluting stents (DES). While DES have dramatically reduced restenosis rates, their use has been associated with an increased risk of late stent thrombosis and accelerated neointimal atherosclerosis (i.e. "neoatherosclerosis") both major contributors to late stent failure. The underlying substrate of late DES failure is likely related to vascular endothelial dysfunction such as poor endothelial regrowth and barrier function (i.e. "endothelial healing"). Initial concerns with 1st generation DES have lead to improvements in mechanical and biologic properties of current 2nd generation DES, which inhibit endothelial regrowth to a lesser extent, lessening late stent failure and resulting in an overall improved safety profile. Current guidelines recommend duration of at least one year of dual anti-platelet therapy with aspirin and a thienopyridine agent such as clopidogrel or prasugrel as sufficient to prevent late thrombotic complications. Recent studies, however, suggest a shorter duration of dual anti-platelet therapy may be equally as safe and efficacious in preventing stent thrombosis with newer generation DES. However, higher risk populations such as patients receiving 1st generation DES or those with increased risk for future ischemic events may benefit from a longer duration (i.e. 30 months) of DAPT to prevent major cardiovascular events with the caveat that such an approach may be associated with an increased risk for bleeding. This review examines the vascular responses to 1st and second generation DES and recent clinical trials examining DAPT duration. PMID:25533811

  9. Chronic anti-platelet therapy: a contraindication for platelet-rich plasma intra-articular injections?

    PubMed

    Di Matteo, B; Filardo, G; Lo Presti, M; Kon, E; Marcacci, M

    2014-01-01

    We report the case of a 50 years-old man who complained persisting knee pain that limited almost completely his sport performance. Since he previously underwent multiple aortocoronaric by-passes, he presented a chronic anti-aggregant therapy. In spite of this clinical history, he was still sport active and able to run long-distance races, until knee symptoms limited is activity level. Conservative treatment approaches proved to be unsuccessful, thus we decided to treat him by 3 Platelet-rich Plasma (PRP) injections even if chronic anti-aggregant therapy is generally regarded as a contra-indication for PRP, since this kind of drugs impairs platelet function and granules' release. Despite these premises, the clinical outcome was very satisfactory and the patient was able to rapidly resume intensive running activity. This experience opens new questions regarding the real potential of PRP in treating degenerative musculo-skeletal disorders, and in particular on its range of biological actions and on its limitations for clinical application. PMID:24825043

  10. Bridging Anti-Platelet Therapy With the Intravenous Agent Cangrelor In Patients Undergoing Cardiac Surgery

    PubMed Central

    Angiolillo, Dominick J; Firstenberg, Michael S.; Price, Matthew J.; Tummala, Pradyumna E.; Hutyra, Martin; Welsby, Ian J.; Voeltz, Michele D.; Chandna, Harish; Ramaiah, Chandrashekhar; Brtko, Miroslav; Cannon, Louis; Dyke, Cornelius; Liu, Tiepu; Montalescot, Gilles; Manoukian, Steven V.; Prats, Jayne; Topol, Eric J.

    2013-01-01

    Context Thienopyridines are among the most widely prescribed medications, but their use can be complicated by the unanticipated need for surgery. Despite increased risk of thrombosis, guidelines recommend discontinuing thienopyridines 5–7 days prior to surgery to minimize bleeding. Objective To evaluate the use of cangrelor, an intravenous, reversible P2Y12 platelet inhibitor for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG). Design, Setting, and Patients Prospective, randomized double-blind, placebo-controlled, multicenter trial, in patients (n=210) with an acute coronary syndrome (ACS) or treated with a coronary stent on a thienopyridine awaiting CABG to receive either cangrelor or placebo after an initial open-label, dose-finding phase (n=11) conducted between January 2009 and April 2011. Interventions Thienopyridines were stopped and patients administered cangrelor or placebo for at least 48 hours, which was discontinued 1–6 hours prior to CABG. Main outcome measures The primary efficacy endpoint was platelet reactivity (measured in P2Y12 Reaction Units [PRU]), assessed daily with the VerifyNow™ P2Y12 assay. The main safety endpoint was excessive CABG-related bleeding. Results The dose of cangrelor determined in the open-label stage was 0.75 µg/kg/min. In the randomized phase, a greater proportion of patients treated with cangrelor had low levels of platelet reactivity throughout the entire treatment period compared with placebo (primary endpoint, PRU<240: 98.8% (83/84) vs. 19.0% (16/84); relative risk [RR]: 5.2, 95% confidence interval [CI]:3.3–8.1, p<0.001). Excessive CABG-related bleeding occurred in 11.8% (12/102) vs. 10.4% (10/96) in the cangrelor and placebo groups, respectively (RR=1.1, 95% CI: 0.5–2.5, p=0.763). There were no significant differences in major bleeding prior to CABG, although minor bleeding was numerically higher with cangrelor. Conclusions Among patients who must wait for cardiac surgery

  11. Anti-Platelet Therapy is Associated With Decreased Transfusion-Associated Risk of Lung Dysfunction, Multiple Organ Failure, and Mortality in Trauma Patients

    PubMed Central

    Harr, Jeffrey N.; Moore, Ernest E.; Johnson, Jeffrey; Chin, Theresa L.; Wohlauer, Max V.; Maier, Ronald; Cuschieri, Joseph; Sperry, Jason; Banerjee, Anirban; Silliman, Christopher C.; Sauaia, Angela

    2012-01-01

    Objective To determine whether pre-hospital anti-platelet therapy (APT) was associated with reduced incidence of acute lung dysfunction, multiple organ failure (MOF), and mortality in blunt trauma patients. Design Secondary analysis of a cohort enrolled in the NIGMS Trauma Glue Grant database. Setting Multicenter study including 9 US level-1 trauma centers. Patients A total of 839 severely injured blunt trauma patients at risk for MOF (age >45 years, base deficit > 6 mEq/L or systolic blood pressure < 90 mmHg, who received a blood transfusion). Severe/isolated head injuries were excluded. Measurements and Main Results Primary outcomes were lung dysfunction (defined as grades 2–3 by the Denver MOF score), MOF (Denver MOF score>3), and mortality. Patients were documented as on APT if taking acetylsalicylic acid, clopidogrel, and/or ticlopidine. Fifteen percent were taking APT prior to injury. Median injury severity score (ISS) was 30 (interquartile range, IQR: 22–51), mean age 61 ± 0.4 years and median red blood cells (RBC) volume transfused was 1700 ml (IQR: 800–3150ml). Overall, 63% developed lung dysfunction, 19% had MOF, and 21% died. After adjustment for age, gender, comorbidities, blood products, crystalloid/12hrs, presence of any head injury, ISS, and 12hrs base deficit >8 mEq/L, 12 hrs RBC transfusion was associated with a significantly smaller risk of lung dysfunction and MOF among the group receiving APT compared to those not receiving it (lung dysfunction p=0.0116, MOF p=0.0291). In addition, APT had a smaller risk (albeit not significant, p=0.06) of death for patients receiving RBC compared to those not on APT after adjustment for confounders, Conclusions Pre-injury APT therapy is associated with a decreased risk of lung dysfunction, MOF, and possibly mortality in high-risk blunt trauma patients who received blood transfusions. These findings suggest platelets have a role in organ dysfunction development and have potential therapeutic implications

  12. It Is Not Mandatory to Use Triple Rather Than Dual Anti-Platelet Therapy After a Percutaneous Coronary Intervention With a Second-Generation Drug-Eluting Stent

    PubMed Central

    Kim, Ju-Youn; Choi, Yun-Seok; Kwon, Ami; Chung, Woo-Baek; Park, Chul-Soo; Kim, Hee-Yeol; Chang, Kiyuk; Lee, Man-Young; Chung, Wook-Sung; Seung, Ki-Bae

    2015-01-01

    Abstract It has been shown that triple antiplatelet therapy with cilostazol results in better clinical outcomes than dual therapy in patients treated with a first-generation drug-eluting stent (DES); however, it is unclear whether triple antiplatelet therapy has a similar efficacy after the implantation of second-generation DES. In the COACT (Cath Olic medical center percutAneous Coronary in Tervention) registry, 1248 study subjects who underwent percutaneous coronary intervention with an everolimus- or zotarolimus-eluting stent (Endeavor, Xience V, or Promus) were analyzed. The patients were divided into 2 groups after propensity score matching (n = 724; M = 422 [58.3%]; mean age = 66.1 ± 11.0 years): Group 1: patients treated with dual antiplatelet drugs (aspirin and clopidogrel; n = 362; M = 213 [58.8%]; mean age = 65.6 ± 11.7 years); Group 2: patients treated with triple antiplatelet drugs (aspirin, clopidogrel, and cilostazol; n = 362; M = 209 [57.7%]; mean age = 65.6 ± 11.7 years). The mean follow-up duration was 13 ± 10 months, and the cumulative incidence of major cardiovascular events (MACE) was 6.3% in Group 1 and 7.7% in Group 2. There were no significant differences in MACE (death, nonfatal myocardial infarction, and stroke) between the 2 groups (OR, 1.210; 95% CI: 0.772–1.898; P = 0.406). Kaplan–Meier curves for MACE did not show any survival benefit for triple antiplatelet therapy, even in patients with acute coronary syndrome. In patients treated with a second-generation DES implantation, there is no added clinical benefit to using triple rather than dual antiplatelet therapy. PMID:26579817

  13. Anti-platelet therapy: phosphodiesterase inhibitors

    PubMed Central

    Gresele, Paolo; Momi, Stefania; Falcinelli, Emanuela

    2011-01-01

    Inhibition of platelet aggregation can be achieved either by the blockade of membrane receptors or by interaction with intracellular signalling pathways. Cyclic adenosine 3′,5′-monophosphate (cAMP) and cyclic guanosine 3′,5′-monophosphate (cGMP) are two critical intracellular second messengers provided with strong inhibitory activity on fundamental platelet functions. Phosphodiesterases (PDEs), by catalysing the hydrolysis of cAMP and cGMP, limit the intracellular levels of cyclic nucleotides, thus regulating platelet function. The inhibition of PDEs may therefore exert a strong platelet inhibitory effect. Platelets possess three PDE isoforms (PDE2, PDE3 and PDE5), with different selectivity for cAMP and cGMP. Several nonselective or isoenzyme-selective PDE inhibitors have been developed, and some of them have entered clinical use as antiplatelet agents. This review focuses on the effect of PDE2, PDE3 and PDE5 inhibitors on platelet function and on the evidence for an antithrombotic action of some of them, and in particular of dipyridamole and cilostazol. PMID:21649691

  14. Early Clinical Experience with a Polymer-Free Biolimus A9 Drug-Coated Stent in DES-Type Patients Who Are Poor Candidates for Prolonged Dual Anti-Platelet Therapy

    PubMed Central

    Kinnaird, Tim; Butt, Mehmood; Abdul, Fairoz; Yazji, Khaled; Hailan, Ahmed; Gallagher, Sean; Ossei-Gerning, Nicholas; Chase, Alexander; Choudhury, Anirban; Smith, David; Anderson, Richard

    2016-01-01

    Introduction Prolonged dual anti-platelet therapy (DAPT) may cause excess bleeding in certain patients. The biolimus-A9 drug-coated stent (BA9-DCS) has a rapid drug-elution profile allowing shortened DAPT. Data were gathered on the early experience implanting this stent in drug-eluting stent eligible patients deemed to be at high risk of bleeding. Background and Methods The demographics, procedural data and clinical outcomes were gathered prospectively for 249 patients treated with a BA9-DCS stent at 2 UK centres, and compared to a cohort of patients treated in the same period with drug-eluting stents (PCI-DES). Results Operator-defined BA9-DCS indications included warfarin therapy, age, and anaemia. Patients receiving a BA9-DCS were older (71.6±11.8 vs. 64.8±11.6yrs, p<0.001), more often female (38.2 vs. 26.8%, P<0.001), and more likely to have comorbidity including chronic kidney disease or poor LV function than PCI-DES patients. The baseline Mehran bleed risk score was also significantly higher in the BA9-DCS group (19.4±8.7 vs. 13.1±5.8, p<0.001). Of the BA9-DCS cohort, 95.5% of patients demonstrated disease fitting NICE criteria for DES placement. The number of lesions treated (1.81±1.1 vs. 1.58±0.92, p = 0.003), total lesion length (32.1±21.7 vs. 26.1±17.6mm, p<0.001), number of stents used (1.93±1.11 vs. 1.65±1.4, p = 0.007) and total stent length (37.5±20.8 vs. 32.4±20.3, p<0.01) were greater for BA9-DCS patients. DAPT was prescribed for 3.3±3.9 months for BA9-DCS patients and 11.3±2.4 months for PCI-DES patients (p<0.001). At follow up of 392±124 days despite the abbreviated DAPT course stent related event were infrequent with ischemia-driven restenosis PCI (2.8 vs. 3.4%, p = 0.838), and stent thrombosis (1.6 vs. 2.1%, p = 0.265) rates similar between the BA9-DCS ad PCI-DES groups. After propensity scoring all clinical end-points were similar between both cohorts. Conclusions This early experience using polymer-free BA9 drug-coated stents in

  15. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin

    PubMed Central

    Bozzi, Laura M.; Mitchell, Braxton D.; Lewis, Joshua P.; Ryan, Kathy A.; Herzog, William R.; O’Connell, Jeffrey R.; Horenstein, Richard B.; Shuldiner, Alan R.; Yerges-Armstrong, Laura M.

    2016-01-01

    Clopidogrel and aspirin are commonly prescribed anti-platelet medications indicated for patients who have experienced, or are at risk for, ischemic cardiovascular events. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study was designed to characterize determinants of clopidogrel and dual anti-platelet therapy (DAPT) response in a healthy cohort of Old Order Amish from Lancaster, PA. Following a loading dose, clopidogrel was taken once a day for 7 days. One hour after the last dose of clopidogrel, 325 mg of aspirin was given. Ex vivo platelet aggregometry was performed at baseline, post-clopidogrel, and post-DAPT. Platelet aggregation measurements were significantly lower after both interventions for all agonists tested (p <0.05), although there was large inter-individual variation in the magnitude of anti-platelet response. Female sex and older age were associated with higher platelet aggregation at all three time-points. Change in aggregation was correlated among the various agonists at each time point. Heritability (h2) of change in platelet aggregation was significant for most traits at all time-points (range h2=0.14–0.57). Utilization of a standardized, short-term intervention provided a powerful approach to investigate sources of variation in platelet aggregation response due to drug therapy. Further, this short-term intervention approach may provide a useful paradigm for pharmacogenomics studies. PMID:26374108

  16. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin.

    PubMed

    Bozzi, Laura M; Mitchell, Braxton D; Lewis, Joshua P; Ryan, Kathy A; Herzog, William R; O'Connell, Jeffrey R; Horenstein, Richard B; Shuldiner, Alan R; Yerges-Armstrong, Laura M

    2016-01-01

    Clopidogrel and aspirin are commonly prescribed anti-platelet medications indicated for patients who have experienced, or are at risk for, ischemic cardiovascular events. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study was designed to characterize determinants of clopidogrel and dual anti-platelet therapy (DAPT) response in a healthy cohort of Old Order Amish from Lancaster, PA. Following a loading dose, clopidogrel was taken once a day for 7 days. One hour after the last dose of clopidogrel, 325 mg of aspirin was given. Ex vivo platelet aggregometry was performed at baseline, post-clopidogrel, and post-DAPT. Platelet aggregation measurements were significantly lower after both interventions for all agonists tested (p <0.05), although there was large inter-individual variation in the magnitude of anti-platelet response. Female sex and older age were associated with higher platelet aggregation at all three time-points. Change in aggregation was correlated among the various agonists at each time point. Heritability (h2) of change in platelet aggregation was significant for most traits at all time-points (range h2=0.14-0.57). Utilization of a standardized, short-term intervention provided a powerful approach to investigate sources of variation in platelet aggregation response due to drug therapy. Further, this short-term intervention approach may provide a useful paradigm for pharmacogenomics studies. PMID:26374108

  17. Intracranial hemorrhage and platelet transfusion after administration of anti-platelets agents: Fukushima Prefecture.

    PubMed

    Suzuki, Yuhko; Sato, Taku; Sakuma, Jun; Ichikawa, Masahiro; Kishida, Yugo; Oda, Keiko; Watanabe, Yoichi; Goto, Takeshi; Sato, Masahiro; Nollet, Kenneth E; Saito, Kiyoshi; Ohto, Hitoshi

    2016-06-01

    We conducted a case series study to assess intracerebral hemorrhage (ICH) in the context of anti-platelets agents (APAs) and platelet (PLT) transfusion in Fukushima Prefecture.This study included patients who were newly diagnosed with ICH between January 2008 and June 2014 in the neurosurgical hospitals of Fukushima Prefecture. Four of ten neurosurgical hospitals responded to our questionnaire. Of 287 ICH patients, 51 (20.6%) were on APA therapy, of whom PLT transfusion was given to only one persistently bleeding patient who was on dual anti-platelet therapy. In a follow-up survey, 30 out of 51 ICH patients on APA therapy, average age 75 years, were analyzed, of whom 21 (70%) were male. The predominant underlying disease was diabetes mellitus. It is interesting to note that peripheral artery disease and aortic aneurysm were among the indications for APAs. ICH was mainly observed supratentorially. Hematoma enlargement was observed in 13 (44.8%) cases. By day 7, 3 patients (10%) had died from complications of ICH. In this study, we show that ICH during APA therapy matched what was observed in Kanagawa Prefecture. Whether or not a national survey differs, we anticipate greater statistical validity and an opportunity to improve patient outcomes in Japan and around the world. PMID:27210309

  18. Haemobilia causing cholangitis in a patient on dual anti-platelet treatment suffering from acute acalculous cholecystitis

    PubMed Central

    Luhmann, Andreas; Buter, Anton; Abela, Jo-Etienne

    2013-01-01

    INTRODUCTION Haemobilia is a rare cause of upper gastro-intestinal haemorrhage which can be difficult to diagnose. PRESENTATION OF CASE We present the case of a patient who suffered from acute acalculous cholecystitis while on dual anti-platelet therapy with aspirin and clopidogrel. We describe the diagnostic and treatment challenges arising from the patient's complicated past history and the steps leading to the diagnosis of haemobilia causing biliary obstruction and cholangitis. Our patient did not, at any point, manifest anaemia or evidence of haemorrhage. DISCUSSION Haemobilia has a varied aetiology. To our knowledge there is no association with dual anti-platelet treatment in the literature to date. Diagnosis is difficult and relies on multiple modalities. In our patient the final diagnosis was only made in the course of open bile duct exploration. CONCLUSION In acute biliary obstruction we recommend the consideration of haemobilia in the differential diagnosis, especially in patients with a bleeding tendency. PMID:23466686

  19. Anti-platelet drugs attenuate the expansion of circulating CD14highCD16+ monocytes under pro-inflammatory conditions

    PubMed Central

    Layne, Kerry; Di Giosia, Paolo; Ferro, Albert; Passacquale, Gabriella

    2016-01-01

    Aims Levels of circulating CD14highCD16+ monocytes increase in atherosclerotic patients and are predictive of future cardiovascular events. Platelet activation has been identified as a crucial determinant in the acquisition of a CD16+ phenotype by classical CD14highCD16− cells. We tested the hypothesis that anti-platelet drugs modulate the phenotype of circulating monocytes. Methods and results Sixty healthy subjects undergoing influenza immunization were randomly assigned to either no treatment or anti-platelet therapy, namely aspirin 300 mg or 75 mg daily, or clopidogrel (300 mg loading dose followed by 75 mg), for 48 h post-immunization (n = 15/group). Monocyte subsets, high-sensitivity C-reactive protein, pro-inflammatory cytokines, and P-selectin were measured at baseline and post-immunization. The CD14highCD16+ monocyte cell count rose by 67.3% [interquartile range (IQR): 35.7/169.2; P = 0.0002 vs. baseline] in untreated participants. All anti-platelet regimes counteracted expansion of this monocytic subpopulation. Although no statistical differences were noted among the three treatments, aspirin 300 mg was the most efficacious compared with the untreated group (−12.5% change from baseline; IQR: −28.7/18.31; P = 0.001 vs. untreated). Similarly, the rise in P-selectin (17%; IQR: −5.0/39.7; P = 0.03 vs. baseline) observed in untreated participants was abolished by all treatments, with aspirin 300 mg exerting the strongest effect (−30.7%; IQR: −58.4/−0.03; P = 0.007 vs. untreated). Changes in P-selectin levels directly correlated with changes in CD14highCD16+ cell count (r = 0.5; P = 0.0002). There was a similar increase among groups in high-sensitivity C-reactive protein (P < 0.03 vs. baseline levels). Conclusions Anti-platelet drugs exert an immunomodulatory action by counteracting CD14highCD16+ monocyte increase under pro-inflammatory conditions, with this effect being dependent on the amplitude of P-selectin reduction. PMID:27118470

  20. Study of a humanized inhibitory anti-platelet glycoprotein VI phage antibody from a phage antibody library.

    PubMed

    Liu, Qinghong; Zhang, Chunmei; Yu, Lingjia; Shi, Yongyu; Zhang, Liping; Peng, Jun; Ji, Xuebin; Hou, Ming

    2016-01-01

    Objective The aims of the study were to study the effect of anti-platelet glycoprotein (GP) VI auto-antibodies on platelet aggregation and use phage surface display technology to produce anti-platelet GPVI phage antibody fragment, which may be developed to inhibit platelet aggregation in the treatment of cardiovascular disease. Methods Plasma samples from patients with immune thrombocytopenia (ITP) were screened by monoclonal antibody immobilization of the platelet antigen assay and the platelet aggregation test for anti-platelet GPVI auto-antibody with an inhibitory effect. The humanized anti-platelet GPVI phage antibody was produced by phage surface display technology. The function of the phage antibody fragment against platelet aggregation was examined by the platelet aggregation test. Results Of 726 ITP patients, 2 (0.27%) patients' plasma significantly inhibited platelet aggregation induced by collagen-1. After five rounds of selection, enrichment, and purification, a soluble phage antibody fragment was produced, which can inhibit platelet aggregation induced by collagen-1. The results demonstrate that only a few of the screened anti-platelet GPVI auto-antibodies showed an inhibitory effect on platelet aggregation. Discussion A completely humanized anti-GPVI soluble phage antibody can be produced by phage surface display technology. The antibody was able to specifically block collagen-induced platelet aggregation without influencing the aggregation responses to other agonists. Conclusions Results of the present study suggest that very few anti-platelet GPVI auto-antibodies inhibit the aggregation function of platelet. The humanized anti-platelet GPVI produced by phage surface display technology is promising to be used to inhibit platelet aggregation in the treatment of cardiovascular disease. PMID:26330203

  1. Structural functional and folding scenario of an anti platelet and thrombolytic enzyme crinumin.

    PubMed

    Singh, Kunwar Awaneesh; Singh, Sanjay; Jagannadham, Medicherla V

    2014-07-01

    A folding pattern, conformational stability and therapeutic role of a protein helps in developing a suitable drug. Crinumin, a thrombolytic and anti platelet agent, has been studied for its functional and conformational properties by equilibrium unfolding methods. The crinumin belongs to α+β class of protein and exhibits a non native structure and two molten globule states at different conditions. Two domains in the molecular structure of the protein with altered stability are present that unfold sequentially. The enzyme maintains activity as well as structural integrity even in adverse conditions. These observations provide an understanding of protein folding as well as facilitate the development of a potential drug. PMID:24726528

  2. Comparative of three methods (ELIZA, MAIPA and flow cytometry) to determine anti-platelet antibody in children with ITP.

    PubMed

    Hamidpour, Mohsen; Khalili, Ghader; Tajic, Nader; Shamsian, Bi Bi Shahin; Hamidpour, Rafie

    2014-01-01

    Immune (idiopathic) thrombocytopenic purpurea (ITP) is an autoimmune disease characterized by the increased anti-platelet antibodies in the patient's sera and decreased platelets in the blood circulation. This study has determined and characterized the antiplatelet glycoproteins in children with ITP. Thirty eight children, who were hospitalized with clinical signs of ITP in Mofid Children Hospital (Tehran, Iran) during 18 months, went under our clinical studies in a research project. ELISA, Flow cytometry and MAIPA (Monoclonal Antibody Immobilization of Platelet Antigens) methods were employed to determine serum anti-platelet antibodies level. The anti-platelet antibodies level above mean + 3SD of control group was assumed as positive. The platelet counts ranged between 2 × 10(9)/L and 100 × 10(9)/L. Among the patients 63.5% of them were anti-platelet antibodies positive with ELISA method. Results of platelet lysate method showed that 51.7% of patients had antibodies against platelet antigens. Antibody against platelet GPIIb/IIIa, GPIb/IX and GPIa/IIa using MAIPA method were 48%, 54% and 25% respectively. In flow cytometry 62% of patients showed anti-platelet antibodies. The comparison of three methods shows that since MAIPA is the specific method for the detection of very small amount of antibody against glycoprotein antigens, it has the advantage of differentiating between immune and non-immune thrombocytopenia. PMID:25755908

  3. Comparative of three methods (ELIZA, MAIPA and flow cytometry) to determine anti-platelet antibody in children with ITP

    PubMed Central

    Hamidpour, Mohsen; Khalili, Ghader; Tajic, Nader; Shamsian, Bi Bi Shahin; Hamidpour, Rafie

    2014-01-01

    Immune (idiopathic) thrombocytopenic purpurea (ITP) is an autoimmune disease characterized by the increased anti-platelet antibodies in the patient’s sera and decreased platelets in the blood circulation. This study has determined and characterized the antiplatelet glycoproteins in children with ITP. Thirty eight children, who were hospitalized with clinical signs of ITP in Mofid Children Hospital (Tehran, Iran) during 18 months, went under our clinical studies in a research project. ELISA, Flow cytometry and MAIPA (Monoclonal Antibody Immobilization of Platelet Antigens) methods were employed to determine serum anti-platelet antibodies level. The anti-platelet antibodies level above mean + 3SD of control group was assumed as positive. The platelet counts ranged between 2 × 109/L and 100 × 109/L. Among the patients 63.5% of them were anti-platelet antibodies positive with ELISA method. Results of platelet lysate method showed that 51.7% of patients had antibodies against platelet antigens. Antibody against platelet GPIIb/IIIa, GPIb/IX and GPIa/IIa using MAIPA method were 48%, 54% and 25% respectively. In flow cytometry 62% of patients showed anti-platelet antibodies. The comparison of three methods shows that since MAIPA is the specific method for the detection of very small amount of antibody against glycoprotein antigens, it has the advantage of differentiating between immune and non-immune thrombocytopenia. PMID:25755908

  4. One-year outcome of a prospective trial stopping dual antiplatelet therapy at 3 months after everolimus-eluting cobalt-chromium stent implantation: ShortT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent (STOPDAPT) trial.

    PubMed

    Natsuaki, Masahiro; Morimoto, Takeshi; Yamamoto, Erika; Shiomi, Hiroki; Furukawa, Yutaka; Abe, Mitsuru; Nakao, Koichi; Ishikawa, Tetsuya; Kawai, Kazuya; Yunoki, Kei; Shimizu, Shogo; Akao, Masaharu; Miki, Shinji; Yamamoto, Masashi; Okada, Hisayuki; Hoshino, Kozo; Kadota, Kazushige; Morino, Yoshihiro; Igarashi, Keiichi; Tanabe, Kengo; Kozuma, Ken; Kimura, Takeshi

    2016-07-01

    There has been no previous prospective study evaluating dual antiplatelet therapy (DAPT) duration shorter than 6 months after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation. STOPDAPT trial is a prospective multi-center single-arm study evaluating 3-month DAPT duration after CoCr-EES implantation. The primary endpoint was a composite of cardiovascular death, myocardial infarction (MI), stroke, definite stent thrombosis (ST) and TIMI major/minor bleeding at 1 year. Between September 2012 and October 2013, a total of 1525 patients were enrolled from 58 Japanese centers, with complete 1-year follow-up in 1519 patients (99.6 %). Thienopyridine was discontinued within 4 months in 1444 patients (94.7 %). The event rates beyond 3 months were very low (cardiovascular death: 0.5 %, MI: 0.1 %, ST: 0 %, stroke: 0.7 %, and TIMI major/minor bleeding: 0.8 %). Cumulative 1-year incidence of the primary endpoint was 2.8 % [upper 97.5 % confidence interval (CI) 3.6 %], which was lower than the pre-defined performance goal of 6.6 % (P < 0.0001). Using the CoCr-EES group in the RESET trial as a historical comparison group, where nearly 90 % of patients had continued DAPT at 1 year, cumulative incidence of the primary endpoint tended to be lower in the STOPDAPT than in the RESET (2.8 versus 4.0 %, P = 0.06) and adjusted hazard ratio was 0.64 (95 % CI 0.42-0.95, P = 0.03). The cumulative incidence of definite/probable ST was lower in the STOPDAPT than in the RESET [0 patient (0 %) versus 5 patients (0.3 %), P = 0.03]. In conclusion, stopping DAPT at 3 months in selected patients after CoCr-EES implantation was at least as safe as the prolonged DAPT regimen adopted in the historical control group. PMID:26518420

  5. [Anti-platelet aggregation bioassay based quality control for XST capsules].

    PubMed

    Han, Bing; Mao, Xin; Han, Shu-xian; Chen, Ying; Xiang, Yan-hua; Ge, Yi-meng; Liao, Fu-long; You, Yun

    2015-12-01

    A in vitro platelet aggregation bioassay was developed for the quality control of XST capsules. The in vitro anti-platelet aggregation effect in rats was observed to detect the bioactivity of XST capsules. Panax notoginseng saponins and Xuesaitong lyophilizedpowder for injection were taken as standard control substances to determine the potency. According to the results, XST capsules showeda significant inhibitory effect on thrombin-induced platelet aggregation in a dose-dependent manner. The in vitro anti-platelet activity oflyophilized powder for injection was stabler than that of Panax notoginseng saponins, and so suitable to serve as a standard control substance. The biological potency of XST capsules compared with standard control substance was detected by using parallel line assay. According to the results, the established bioassay method had a good repeatability (RSD 2.92%). The sample test results could pass thereliability test(linear deviation P > 0.05, parallel deviation P > 0.05). This bioassay method could be used as one of the complementary quality control methods for XST capsules. PMID:27141669

  6. Experimental evaluation of analgesic, anti-inflammatory and anti-platelet potential of Dashamoola

    PubMed Central

    Parekar, Reshma R.; Bolegave, Somesh S.; Marathe, Padmaja A.; Rege, Nirmala N.

    2015-01-01

    Background: Dashamoola, in the form of arishta and kwath, is a commonly used classical Ayurvedic multi-ingredient formulation for management of pain, arthritis and inflammatory disorders. Objective: To study analgesic, anti-inflammatory and anti-platelet activity of Dashamoola and its combination with aspirin. Materials and Methods: Wistar albino rats (180-200 g) and Swiss albino mice (20-25 g) of either sex were divided randomly into five groups: Distilled water, aspirin (500mg/kg in rats; 722.2 mg/kg in mice), Dashamoolarishta (1.8 mL/kg in rats; 2.5 mL/kg in mice) and Dashamoolarishta with aspirin. Anti-inflammatory activity was measured by change in paw volume in carrageenan-induced inflammation, protein content in model of peritonitis and granuloma weight in cotton pellet granuloma. Analgesic effect was evaluated by counting number of writhes in writhing model. Maximum platelet aggregation and percentage inhibition of ADP and collagen-induced platelet aggregation were estimated in vitro. Statistical analysis was done using one way ANOVA (post hoc Tukey's test) and P < 0.05 was considered significant. Results: Dashamoolarishta and its combination with aspirin showed significantly (P < 0.01) less number of writhes. It showed significant (P < 0.001) anti-inflammatory activity by paw edema reduction in rats, decrease in proteins in peritoneal fluid (P < 0.001) and decrease in granuloma weight (P < 0.05) as compared to respective vehicle control groups. Dashamoola kwath alone and in combination with aspirin inhibited maximum platelet aggregation and percent inhibition of platelets as compared to vehicle (P < 0.001). Conclusion: Dashamoola formulation alone and its combination with aspirin showed comparable anti-inflammatory, analgesic and anti-platelet effects to aspirin. PMID:25878458

  7. Novel uses for anti-platelet agents as anti-inflammatory drugs

    PubMed Central

    Pitchford, S C

    2007-01-01

    An alteration in the character and function of platelets is manifested in patients with inflammatory diseases, and these alterations have been dissociated from the well-characterized involvement of platelets in thrombosis and haemostasis. Recent evidence reveals platelet activation is sometimes critical in the development of inflammation. The mechanisms by which platelets participate in inflammation are diverse, and offer numerous opportunities for future drug intervention. There is now acceptance that platelets act as innate inflammatory cells in immune responses, with roles as sentinel cells undergoing surveillance, responding to microbial invasion, orchestrating leukocyte recruitment, and migrating through tissue, causing damage and influencing repair processes in chronic disease. Some of these processes are targeted by drugs that are being developed to target platelet participation in atherosclerosis. The actions of platelets therefore influence the pathogenesis of diverse inflammatory diseases in various body compartments, encompassing parasitic and bacterial infection, allergic inflammation (especially asthma and rhinitis), and non-atopic inflammatory conditions, for example, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and atherosclerosis. This review will first discuss the evidence for platelet activation in these various inflammatory diseases, and secondly discuss the mechanisms by which this pathogenesis occurs and the various anti-platelet agents which have been developed to combat platelet activation in atherosclerosis and their potential future use for the treatment of other inflammatory diseases. PMID:17603547

  8. Anti-platelet activity of a three-finger toxin (3FTx) from Indian monocled cobra (Naja kaouthia) venom.

    PubMed

    Chanda, Chandrasekhar; Sarkar, Angshuman; Sistla, Srinivas; Chakrabarty, Dibakar

    2013-11-22

    A low molecular weight anti-platelet peptide (6.9 kDa) has been purified from Naja kaouthia venom and was named KT-6.9. MALDI-TOF/TOF mass spectrometry analysis revealed the homology of KT-6.9 peptide sequence with many three finger toxin family members. KT-6.9 inhibited human platelet aggregation process in a dose dependent manner. It has inhibited ADP, thrombin and arachidonic acid induced platelet aggregation process in dose dependent manner, but did not inhibit collagen and ristocetin induced platelet aggregation. Strong inhibition (70%) of the ADP induced platelet aggregation by KT-6.9 suggests competition with ADP for its receptors on platelet surface. Anti-platelet activity of KT-6.9 was found to be 25 times stronger than that of anti-platelet drug clopidogrel. Binding of KT-6.9 to platelet surface was confirmed by surface plasma resonance analysis using BIAcore X100. Binding was also observed by a modified sandwich ELISA method using anti-KT-6.9 antibodies. KT-6.9 is probably the first 3 FTx from Indian monocled cobra venom reported as a platelet aggregation inhibitor. PMID:24183721

  9. Sequestration of anti-platelet GPIIIa antibody in rheumatoid factor immune complexes of human immunodeficiency virus 1 thrombocytopenic patients.

    PubMed Central

    Karpatkin, S; Nardi, M A; Hymes, K B

    1995-01-01

    Human immunodeficiency virus 1-related idiopathic thrombocytopenic purpura (HIV-1-ITP) patients have a 4-fold increased percentage of CD5+ B cells and a 4.8-fold increased percentage of serum immune complexes precipitated by polyethylene glycol (PEG-ICs) compared to control subjects, as reported previously. Since CD5+ B cells produce predominantly IgM rheumatoid factor (RF) vs. Fc of IgG and PEG-ICs contain high levels of IgM, we looked for the presence of RF in the immune complexes of HIV-1-ITP patients. PEG-ICs were adsorbed to protein A and dissociated with acid, and IgM and IgG were purified by gel filtration and affinity chromatography. Solid-phase ELISA was used to measure antibody specificity vs. platelets, Fc, and HIV-1 gp120, p24, and CD4. Dissociated IgG antibody reacted with platelets, HIV-1 gp120, p24, and CD4, but not with Fc. Serum IgG did not react with platelets or Fc but did react with HIV-1 gp120, p24, and CD4. Both PEG-IC IgM and serum IgM reacted with Fc as well as the other four antigens. Control IgM and IgG were unreactive. Isolated IgM from PEG-ICs relocated approximately 50% of the IgG preincubated with IgM to the Vo region of a G200 gel-filtration column. Anti-platelet IgG but not IgM could be affinity-purified from fixed platelets. Both F(ab')2 fragments of anti-platelet IgG and the total PEG-IC bound to platelets in a saturation-dependent manner. F(ab')2 of anti-platelet IgG inhibited 50% binding of PEG-IC to platelets at an F(ab')2/complex ratio of 3:1 (wt/wt). Scatchard analysis revealed two classes of binding sites: high-affinity Kd values of 0.8-1.8 nM and lower-affinity Kd values of 6.6-12.3 nM with respective numbers of binding sites of 44,000-57,000 and 122,000-256,000 (n = 4). Anti-platelet IgG of 6/6 patients precipitated GPIIIa from platelet lysates of surface 125I-labeled platelets. Platelet count correlated inversely with anti-platelet IgG (r = -0.73; P < 0.01; n = 27). Thus, PEG-ICs of HIV-1-ITP patients contain IgM RF, which

  10. Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population.

    PubMed

    Veach, Daniel; Hosking, Holly; Thompson, Kiara; Santhakumar, Abishek Bommannan

    2016-08-10

    This ex vivo study was performed to evaluate the anti-platelet and anti-thrombogenic potential of shikimic acid (SA), a plant phenolic metabolite. Fasting blood samples were collected from 22 sedentary participants to analyse the effect of varying concentrations of SA (0.1 mM, 0.2 mM, 0.5 mM, 1 mM and 2 mM) on platelet surface-marker expression, platelet aggregation and biomarkers of thrombogenesis. Monocyte-platelet aggregates (CD14/CD42b) and platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31), effective indicators of thrombus formation were evaluated. Procaspase-activating compound 1 (PAC-1) and P-selectin or CD62P were used to assess platelet activation-related thrombogenesis. Adenosine diphosphate (ADP) was used to stimulate the P2Y1/P2Y12 pathway of platelet activation to mimic the in vivo thrombogenic pathway. Platelet aggregation studies utilised both ADP and collagen as exogenous platelet agonists to target both P2Y1/P2Y12 and GPVI pathways of thrombus formation. It was observed with flow cytometry that SA produced a significant antiplatelet effect on PAC-1 (p = 0.03 at 2 mM) and CD62P (p = 0.017, p = 0.036 at 1 mM and 2 mM respectively) expression in addition to lowering monocyte-platelet aggregate formation (p = 0.013, p < 0.01 and p < 0.01 at 0.5 mM, 1 mM and 2 mM respectively). SA at 1 mM concentration reduced PECAM-1 expression (p = 0.035), signifying a reduction to endothelial leucocyte migration during thrombus growth. SA did not demonstrate a platelet aggregation inhibitory effect by targeting the GPVI collagen pathway but reduced ADP induced platelet aggregation at 2 mM concentration (p < 0.01 at 2 mM). The results suggest that SA, an active metabolite of polyphenol-rich food intake, could play an important role in reducing platelet activation, aggregation related thrombus formation and biomarkers of thrombogenesis in sedentary individuals. PMID:27480079

  11. Anti-platelet antibodies associated with the Canale–Smith syndrome bind to the same platelet glycoprotein complexes as those of idiopathic thrombocytopenic purpura patients

    PubMed Central

    GRODZICKY, T; BUSSEL, J B; ELKON, K B

    2002-01-01

    The Canale–Smith syndrome (CSS) is an inherited disease characterized by massive lymphadenopathy, hepatosplenomegaly and systemic autoimmunity to erythrocytes and platelets. Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease in which approximately 60–80% of patients have anti-platelet antibodies directed against specific platelet glycoprotein complexes (GPCs) located on their membrane: GP IIb/IIIa, GPIb/IX, and GPIa/IIa. Almost all (95–100%) of the antibody-positive patients have antibodies directed against GPIIb/IIIa alone, or in combination with other glycoprotein targets. Our objective was to determine the specificities of the anti-platelet antibodies in CSS patients. The detection of anti-platelet antibodies was performed using a commercially available ELISA, the Pak-AUTO (GTI, Brookfield, WI), in which highly purified GPIIb/IIIa, GPIb/IX, and GPIa/IIa are immobilized on microtitre plates, incubated with serum or plasma, and subsequently developed with an antihuman polyclonal immunoglobulin. Of 14 CSS patients tested, 11 (79%) had anti-platelet antibodies in their serum directed toward at least one of the three major GPC, nine (82%) of which were against GPIIb/IIIa alone or in combination. Antibodies detected in the sera of ITP patients had similar specificities. No such antibodies were detected in samples from 25 consecutive normal controls. These results demonstrate that a genetically defined defect in lymphocyte apoptosis results in a humoral autoimmune response with anti-platelet specificities very similar to the common idiopathic form of autoimmune thrombocytopenia. PMID:11876752

  12. A Novel Direct Factor Xa Inhibitory Peptide with Anti-Platelet Aggregation Activity from Agkistrodon acutus Venom Hydrolysates

    PubMed Central

    Chen, Meimei; Ye, Xiaohui; Ming, Xin; Chen, Yahui; Wang, Ying; Su, Xingli; Su, Wen; Kong, Yi

    2015-01-01

    Snake venom is a natural substance that contains numerous bioactive proteins and peptides, nearly all of which have been identified over the last several decades. In this study, we subjected snake venom to enzymatic hydrolysis to identify previously unreported bioactive peptides. The novel peptide ACH-11 with the sequence LTFPRIVFVLG was identified with both FXa inhibition and anti-platelet aggregation activities. ACH-11 inhibited the catalytic function of FXa towards its substrate S-2222 via a mixed model with a Ki value of 9.02 μM and inhibited platelet aggregation induced by ADP and U46619 in a dose-dependent manner. Furthermore, ACH-11 exhibited potent antithrombotic activity in vivo. It reduced paralysis and death in an acute pulmonary thrombosis model by 90% and attenuated thrombosis weight in an arterio-venous shunt thrombosis model by 57.91%, both at a dose of 3 mg/kg. Additionally, a tail cutting bleeding time assay revealed that ACH-11 did not prolong bleeding time in mice at a dose of 3 mg/kg. Together, our results reveal that ACH-11 is a novel antithrombotic peptide exhibiting both FXa inhibition and anti-platelet aggregation activities, with a low bleeding risk. We believe that it could be a candidate or lead compound for new antithrombotic drug development. PMID:26035670

  13. Effects of Clopidogrel Therapy on Oxidative Stress, Inflammation, Vascular Function and Progenitor Cells in Stable Coronary Artery Disease

    PubMed Central

    Ramadan, Ronnie; Dhawan, Saurabh S.; Syed, Hamid; Pohlel, F. Khan; Binongo, Jose Nilo G.; Ghazzal, Ziyad B.; Quyyumi, Arshed A.

    2014-01-01

    Background Traditional cardiovascular risk factors lead to endothelial injury and activation of leucocytes and platelets that initiate and propagate atherosclerosis. We proposed that clopidogrel therapy in patients with stable CAD imparts a pleiotropic effect that extends beyond anti-platelet aggregation to other athero-protective processes. Methods Forty-one subjects were randomized in a double-blind, placebo-controlled crossover study to either clopidogrel 75 mg daily or placebo for 6-weeks, and then transitioned immediately to the other treatment for an additional 6 weeks. We assessed 1) endothelial function as flow-mediated dilation of the brachial artery, 2) arterial stiffness and central augmentation index using applanation tonometry, 3) vascular function as fingertip reactive hyperemia index, 4) inflammation by measuring plasma CD40 ligand and serum high-sensitivity c-reactive protein levels, 5) oxidative stress by measuring plasma aminothiols, and 6) circulating progenitor cells, at baseline and at the end of each 6-week treatment period. Results Clopidogrel therapy resulted in a significant reduction in soluble CD40 ligand (p=0.03), a pro-thrombotic and pro-inflammatory molecule derived mainly from activated platelets. However, clopidogrel therapy had no effect on endothelial function, arterial stiffness, inflammatory and oxidative stress markers, or progenitor cells. Conclusions Our findings suggest a solitary anti-platelet effect of clopidogrel therapy in patients with stable CAD, with no effect on other sub-clinical markers of cardiovascular disease risk. PMID:24336012

  14. Effect of active synthetic 2-substituted quinazolinones on anti-platelet aggregation and the inhibition of superoxide anion generation by neutrophils.

    PubMed

    Chang, Fang-Rong; Wu, Chin-Chung; Hwang, Tsong-Long; Patnam, Ramesh; Kuo, Reen-Yen; Wang, Wei-Ya; Lan, Yu-Hsuan; Wu, Yang-Chang

    2003-07-01

    Quinazolinones, 2-substituted and 3-substituted, mainly synthesized by microwave irradiation, were subjected to anti-platelet aggregation and inhibition of superoxide anion generation assays. Interestingly, 2-phenyl-4-quinazolinone (4) exhibited significant inhibitory activities toward platelet aggregation and neutrophil activation, and it might therefore serve as a prototype lead compound. PMID:12934640

  15. Comparative anti-platelet and antioxidant properties of polyphenol-rich extracts from: berries of Aronia melanocarpa, seeds of grape and bark of Yucca schidigera in vitro.

    PubMed

    Olas, Beata; Wachowicz, Barbara; Tomczak, Anna; Erler, Joachim; Stochmal, Anna; Oleszek, Wieslaw

    2008-02-01

    The aim of the present study was to investigate and compare the anti-platelet action of extracts from three different plants: bark of Yucca schidigera, seeds of grape and berries of Aronia melanocarpa (chokeberry). Anti-platelet action of tested extracts was compared with action of well characterized antioxidative and anti-platelet commercial monomeric polyphenol-resveratrol. The effects of extracts on platelet adhesion to collagen, collagen-induced platelet aggregation and on the production of O2-* in resting platelets and platelets stimulated by a strong platelet agonist-thrombin were studied. The in vitro experiments have shown that all three tested extracts (5-50 microg/ml) rich in polyphenols reduce platelet adhesion, aggregation and generation of O2-* in blood platelets. Comparative studies indicate that all three plant extracts were found to be more reactive in reduction of platelet processes than the solution of pure resveratrol. The tested extracts due to their anti-platelet effects may play an important role as components of human diet in prevention of cardiovascular or inflammatory diseases, where blood platelets are involved. PMID:18231940

  16. Circulating Thrombotic Risk Factors in Young Patients with Coronary Artery Disease Who Are on Statins and Anti-platelet Drugs.

    PubMed

    George, Reema; Sivadasanpillai, Harikrishnan; Jayakumari, Narayani; Bhatt, Anugya; Thulaseedharan, Jissa V; Tharakan, Jaganmohan A

    2016-07-01

    Thrombotic risk factors may contribute to premature coronary artery disease (CAD), in addition to the conventional risk factors. There is paucity of data on studies evaluating the role of thrombotic factors in premature CAD in Indian patients. Thus a case-control study was performed to evaluate the role of thrombotic and atherogenic factors in young patients with angiographically proven CAD who are on treatment with statins and anti-platelet drugs. 152 patients (≤55 years) with angiographically proven CAD and 102 asymptomatic controls were recruited. Clinical and biochemical data were obtained in both groups. Blood levels of thrombotic factors-fibrinogen, antithrombin-III, tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von-Willebrand factor (v-WF), lipoprotein(a) [Lp(a)] and homocysteine were analyzed. Patients had high levels of conventional CAD risk factors (diabetes mellitus, smoking, hypertension, dyslipidemia and positive family history) compared to controls. Logistic regression analysis revealed that low antithrombin-III (odds ratio/OR 11.2; 95 % confidence interval/CI 2.29-54.01), high fibrinogen (OR 6.04; 95 % CI 1.09-33.21) and high Lp(a) (OR 4.54; 95 % CI 0.92-22.56), as important, independent risk factors in patients. PAI-1(OR 0.15; 95 % CI 0.03-0.69) levels were significantly lower in patients. But other thrombotic risk factors studied (t-PA, v-WF and homocysteine) were comparable among patients and controls. The treatment using statins and anti-platelet drugs might be contributing to the control of some of the thrombotic risk factors. The strategies aiming at lowering the levels of thrombotic risk factors along with conventional risk factors may be useful in primary and secondary prevention of CAD. PMID:27382201

  17. Herpetic keratoconjunctivitis: Therapy with synthetic double-stranded RNA

    USGS Publications Warehouse

    Friedman, I.; Evans, C.; Meighan, C.W.; Foote, L.J.; Aiello, P.V.; Park, J.H.; Baron, S.

    1968-01-01

    A study was undertaken in rabbits to determine how late in the course of keratoconjunctivitis caused by herpes simplex recovery could be effected by an inducer of interferon. Interferon was induced by means of synthetic double-stranded RNA copolymer formed with polynosinic acid : polycytidilic acid RNA. Therapy promotes recovery from severe and fully established keratoconjunctivitis for which treatment was begun as late as 3 days after virus inoculation. No drug toxicity was observed in the therapeutic dose range. These findings further support the proposed role of the interferon mechanism in the natural recovery of already established viral infection. They also suggest the usefulness of interferon inducers in viral infections of man.

  18. Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia.

    PubMed

    Sonneveld, Myrthe E; Natunen, Suvi; Sainio, Susanna; Koeleman, Carolien A M; Holst, Stephanie; Dekkers, Gillian; Koelewijn, Joke; Partanen, Jukka; van der Schoot, C Ellen; Wuhrer, Manfred; Vidarsson, Gestur

    2016-07-01

    Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. We recently found IgG Fc-glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. The lowered core-fucosylation increases the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction. Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). Besides a significant decrease in Fc-fucosylation after the first pregnancy (P = 0·0124), Fc-glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. PMID:27017954

  19. Detection and effects on platelet function of anti-platelet antibody in mule foals with experimentally induced neonatal alloimmune thrombocytopenia.

    PubMed

    Ramirez, S; Gaunt, S D; McClure, J J; Oliver, J

    1999-01-01

    Horse mares carrying mule foals were immunized during the last trimester of pregnancy with whole acid-citrate-dextrose-anticoagulated donkey blood to experimentally induce neonatal alloimmune thrombocytopenia. Thrombocytopenia occurred in the neonatal mule foals born to immunized horse mares within 24 hours after ingestion of their dams' colostrum. Mule foals born to mares not immunized with donkey blood did not develop thrombocytopenia. These findings suggest that antibodies may have been directed against a donkey platelet antigen present in the mule foals but not present in their dams. The objectives of this study were to determine whether anti-platelet antibody could be detected in mule foals with experimentally induced neonatal alloimmune thrombocytopenia, to identify any platelet proteins recognized by serum antibody in these foals, and to determine if platelet function was altered by sera from these mule foals. An indirect enzyme-linked immunosorbent assay demonstrated significantly higher absorption at 1:200 of platelet-bindable immunoglobulin G in serum from thrombocytopenic mule foals, compared with nonthrombocytopenic mule foals. Sera from thrombocytopenic and nonthrombocytopenic mule foals produced similar binding patterns in western immunoblots with donkey platelet proteins separated on sodium dodecyl sulfate polyacrylamide gels. Maximal platelet aggregation and relative slope of aggregation in response to collagen were significantly inhibited after incubation with sera from thrombocytopenic mule foals. These results suggest that mule foals with induced alloimmune thrombocytopenia have serum antibodies that bind to platelets and may compete with collagen binding sites to impair platelet aggregation. PMID:10587252

  20. Phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) by the anti-platelet drug, cilostazol, in platelets.

    PubMed

    Sudo, Toshiki; Ito, Hideki; Kimura, Yukio

    2003-09-01

    Vasodilator-stimulated phosphoprotein (VASP) is a regulator of actin dynamics in platelets and a common substrate of both cAMP- and cGMP-dependent protein kinases (PKA and PKG). Elevations of the cAMP and cGMP concentration have been shown to inhibit platelet aggregation. Intracellular levels of cAMP and cGMP are regulated by the synthesizing system of adenylate cyclases, and hydrolysis by cyclic nucleotide phosphodiesterases (PDEs). The present study examined the effect of the anti-platelet drug, cilostazol, which inhibits PDE3 activity, on VASP phosphorylation in platelets. VASP phosphorylation was examined by immunoblotting with an anti-VASP antibody, M4, and an anti-phospho-VASP antibody, 16C2. Cilostazol phosphorylated VASP at both Ser157 and Ser239 in a concentration-dependent manner, but EHNA (PDE2 inhibitor), dipyridamole and zaprinast (PDE5 inhibitors) did not. Forskolin (adenylate cyclase activator) and sodium nitroprusside (SNP, NO donor) resulted in the VASP phosphorylation, with increase in the cAMP and cGMP level, respectively. Cilostazol increased cAMP, but not cGMP levels, in platelets. EHNA, zaprinast and dipyridamole, had no effect on cAMP and cGMP levels. The PKA/PKG inhibitor, H-89, inhibited VASP phosphorylation by cilostazol. These results demonstrated that cilostazol phosphorylates VASP through the PDE3 inhibition, increase of cAMP level, and PKA activation in platelets. PMID:14602552

  1. Anti-platelet agents augment cisplatin nanoparticle cytotoxicity by enhancing tumor vasculature permeability and drug delivery

    NASA Astrophysics Data System (ADS)

    Pandey, Ambarish; Sarangi, Sasmit; Chien, Kelly; Sengupta, Poulomi; Papa, Anne-Laure; Basu, Sudipta; Sengupta, Shiladitya

    2014-11-01

    Tumor vasculature is critically dependent on platelet mediated hemostasis and disruption of the same can augment delivery of nano-formulation based chemotherapeutic agents which depend on enhanced permeability and retention for tumor penetration. Here, we evaluated the role of Clopidogrel, a well-known inhibitor of platelet aggregation, in potentiating the tumor cytotoxicity of cisplatin nano-formulation in a murine breast cancer model. In vivo studies in murine syngeneic 4T1 breast cancer model showed a significant greater penetration of macromolecular fluorescent nanoparticles after clopidogrel pretreatment. Compared to self-assembling cisplatin nanoparticles (SACNs), combination therapy with clopidogrel and SACN was associated with a 4 fold greater delivery of cisplatin to tumor tissue and a greater reduction in tumor growth as well as higher survival rate. Clopidogrel enhances therapeutic efficiency of novel cisplatin based nano-formulations agents by increasing tumor drug delivery and can be used as a potential targeting agent for novel nano-formulation based chemotherapeutics.

  2. Maternal anti-platelet β3 integrins impair angiogenesis and cause intracranial hemorrhage

    PubMed Central

    Yougbaré, Issaka; Lang, Sean; Yang, Hong; Chen, Pingguo; Zhao, Xu; Tai, Wei-She; Zdravic, Darko; Vadasz, Brian; Li, Conglei; Piran, Siavash; Marshall, Alexandra; Zhu, Guangheng; Tiller, Heidi; Killie, Mette Kjaer; Boyd, Shelley; Leong-Poi, Howard; Wen, Xiao-Yan; Skogen, Bjorn; Adamson, S. Lee; Freedman, John; Ni, Heyu

    2015-01-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening disease in which intracranial hemorrhage (ICH) is the major risk. Although thrombocytopenia, which is caused by maternal antibodies against β3 integrin and occasionally by maternal antibodies against other platelet antigens, such as glycoprotein GPIbα, has long been assumed to be the cause of bleeding, the mechanism of ICH has not been adequately explored. Utilizing murine models of FNAIT and a high-frequency ultrasound imaging system, we found that ICH only occurred in fetuses and neonates with anti–β3 integrin–mediated, but not anti-GPIbα–mediated, FNAIT, despite similar thrombocytopenia in both groups. Only anti–β3 integrin–mediated FNAIT reduced brain and retina vessel density, impaired angiogenic signaling, and increased endothelial cell apoptosis, all of which were abrogated by maternal administration of intravenous immunoglobulin (IVIG). ICH and impairment of retinal angiogenesis were further reproduced in neonates by injection of anti–β3 integrin, but not anti-GPIbα antisera. Utilizing cultured human endothelial cells, we found that cell proliferation, network formation, and AKT phosphorylation were inhibited only by murine anti–β3 integrin antisera and human anti–HPA-1a IgG purified from mothers with FNAIT children. Our data suggest that fetal hemostasis is distinct and that impairment of angiogenesis rather than thrombocytopenia likely causes FNAIT-associated ICH. Additionally, our results indicate that maternal IVIG therapy can effectively prevent this devastating disorder. PMID:25774504

  3. Lack of association between serum paraoxonase-1 activity and residual platelet aggregation during dual anti-platelet therapy.

    PubMed

    Ohmori, Tsukasa; Yano, Yuichiro; Sakata, Asuka; Ikemoto, Tomokazu; Shimpo, Masahisa; Madoiwa, Seiji; Katsuki, Takaaki; Mimuro, Jun; Shimada, Kazuyuki; Kario, Kazuomi; Sakata, Yoichi

    2012-04-01

    High residual platelet aggregability during thienopyridine treatment occurs because of low levels of the active drug metabolite, and is associated with an increased rate of major adverse cardiovascular events. Recent findings suggest that paraoxonase-1 (PON1) is a major determinant for clopidogrel efficacy. The aim of this study was to assess the impact of serum PON1 activity on platelet aggregability in thienopyridine-treated patients. In 72 patients receiving treatment with aspirin and ticlopidine after acute coronary syndrome, various laboratory data including the formation of platelet aggregations induced by agonists were compared with serum PON1 activities, measured as paraoxonase and homocysteine thiolactone hydrolase (HTLase). Serum paraoxonase activity was significantly associated with HTLase activity (R=0.4487, P<0.0001). These PON1 activities were not correlated with any parameters for platelet aggregation, hypertension, sleep apnea, and diabetes mellitus. In contrast, serum PON1 activities seemed to be involved in cardiac function, with brain natriuretic peptide and ejection fraction being significantly correlated with serum HTLase activity (R=-0.2767, P=0.0214) and paraoxonase activity (R=0.2558, P=0.0339), respectively. Paraoxonase activity also demonstrated a significant association with increased levels of ankle-brachial index (R=0.267, P=0.0255). Serum PON1 activities did not influence platelet aggregability during treatment with thienopyridine. However, they might modulate cardiac function after acute coronary syndrome and progression of atherosclerosis. PMID:22115701

  4. Spray-dried solid dispersions containing ferulic acid: comparative analysis of three carriers, in vitro dissolution, antioxidant potential and in vivo anti-platelet effect.

    PubMed

    Nadal, Jessica Mendes; Gomes, Mona Lisa Simionatto; Borsato, Débora Maria; Almeida, Martinha Antunes; Barboza, Fernanda Malaquias; Zawadzki, Sônia Faria; Farago, Paulo Vitor; Zanin, Sandra Maria Warumby

    2016-11-01

    This article aimed to improve the relative solubility and dissolution rate of ferulic acid (FA) by the use of spray-dried solid dispersions (SDs) in order to ensure its in vitro antioxidant potential and to enhance its in vivo anti-platelet effect. These SDs were prepared by spray-drying at 10 and 20% of drug concentration using polyvinylpyrrolidone K30 (PVP-K30), polyethylene glycol 6000 (PEG 6000) and poloxamer-188 (PLX-188) as carriers. SDs and physical mixtures (PM) were characterized by SEM, XRPD, FTIR spectroscopy and TGA analysis. Spray-dried SDs containing FA were successfully obtained. Relative solubility of FA was improved with increasing carrier concentration. PVP-K30 and PEG 6000 formulations showed suitable drug content values close to 100%, whereas PLX-188 presented mean values between 70 and 90%. Agglomerates were observed depending on the carrier used. XRPD patterns and thermograms indicated that spray-drying led to drug amorphization and provided appropriate thermal stability, respectively. FTIR spectra demonstrated no remarkable interaction between carrier and drug for PEG 6000 and PLX-188 SDs. PVP-K30 formulations had changes in FTIR spectra, which denoted intermolecular O-H•••O = C bonds. Spray-dried SDs played an important role in enhancing dissolution rate of FA when compared to pure drug. The free radical-scavenging assay confirmed that the antioxidant activity of PEG 6000 10% SDs was kept. This formulation also provided a statistically increased in vivo anti-platelet effect compared to pure drug. In summary, these formulations enhanced relative solubility and dissolution rate of FA and chosen formulation demonstrated suitable in vitro antioxidant activity and improved in vivo anti-platelet effect. PMID:27032626

  5. Synthesis of Analogues of Gingerol and Shogaol, the Active Pungent Principles from the Rhizomes of Zingiber officinale and Evaluation of Their Anti-Platelet Aggregation Effects

    PubMed Central

    Shih, Hung-Cheng; Chern, Ching-Yuh; Kuo, Ping-Chung; Wu, You-Cheng; Chan, Yu-Yi; Liao, Yu-Ren; Teng, Che-Ming; Wu, Tian-Shung

    2014-01-01

    The present study was aimed at discovering novel biologically active compounds based on the skeletons of gingerol and shogaol, the pungent principles from the rhizomes of Zingiber officinale. Therefore, eight groups of analogues were synthesized and examined for their inhibitory activities of platelet aggregation induced by arachidonic acid, collagen, platelet activating factor, and thrombin. Among the tested compounds, [6]-paradol (5b) exhibited the most significant anti-platelet aggregation activity. It was the most potent candidate, which could be used in further investigation to explore new drug leads. PMID:24599082

  6. Pronounced antitumor effects and tumor radiosensitization of double suicide gene therapy.

    PubMed

    Rogulski, K R; Zhang, K; Kolozsvary, A; Kim, J H; Freytag, S O

    1997-11-01

    The efficacy of HSV-1 thymidine kinase (TK) and Escherichia coli cytosine deaminase (CD) suicide gene therapies as cancer treatments are currently being examined in humans. We demonstrated previously that compared to single suicide gene therapy, greater levels of targeted cytotoxicity and radiosensitization can be achieved in vitro by genetically modifying tumor cells to express CD and HSV-1 TK concomitantly, as a fusion protein. In the present study, the efficacy of the combined double suicide gene therapy/radiotherapy approach was examined in vivo. Nude mice were injected either s.c. or i.m. with 9L gliosarcoma cells expressing an E. coli CD/HSV-1 TK fusion gene. Double suicide gene therapy using 5-fluorocytosine (500 mg/kg) and ganciclovir (30 mg/kg) proved to be markedly better at delaying tumor growth and achieving a tumor cure than single suicide gene therapy, which used 5-fluorocytosine or ganciclovir administered independently. Importantly, double suicide gene therapy was highly effective against large experimental tumors (>2 cm3), reducing tumor volume an average of 99% and producing a 40% tumor cure. Moreover, double suicide gene therapy profoundly potentiated the antitumor effects of radiation. The results indicate that double suicide gene therapy, particularly when coupled with radiotherapy, may represent a highly effective means of eradicating tumors. PMID:9815600

  7. Relationship between ADP-induced platelet-fibrin clot strength and anti-platelet responsiveness in ticagrelor treated ACS patients

    PubMed Central

    Li, Dan-Dan; Wang, Xu-Yun; Xi, Shao-Zhi; Liu, Jia; Qin, Liu-An; Jing, Jing; Yin, Tong; Chen, Yun-Dai

    2016-01-01

    Background Ticagrelor provides enhanced antiplatelet efficacy but increased risk of bleeding and dyspnea. This study aimed to display the relationship between ADP-induced platelet-fibrin clot strength (MAADP) and clinical outcomes in acute coronary syndrome (ACS) patients treated by ticagrelor. Methods Consecutive Chinese-Han patients with ACS who received maintenance dose of ticagrelor on top of aspirin were recruited. After 5-day ticagrelor maintenance treatment, MAADP measured by thrombelastography (TEG) were recorded for the evaluation of ticagrelor anti-platelet reactivity. Pre-specified cutoffs of MAADP > 47 mm for high on-treatment platelet reactivity (HTPR) and MAADP < 31 mm for low on-treatment platelet reactivity (LTPR) were applied for evaluation. The occurrences of primary ischemic cardiovascular events (including a composite of cardiac death, non-fatal myocardial infarction and stroke), the Thrombolysis in Myocardial Infarction (TIMI) defined bleeding events, and ticagrelor related dyspnea were recorded after a follow-up of three months. Results Overall, 176 ACS patients (Male: 79.55%, Age: 59.91 ± 10.54 years) under ticagrelor maintenance treatment were recruited. The value of MAADP ranged from 4.80% to 72.90% (21.27% ± 12.07% on average), with the distribution higher skewed towards the lower values. Using the pre-specific cutoffs for HTPR and LTPR, seven patients (3.98%) were identified as HTPR and 144 patients (81.82%) as LTPR. After a follow-up of three months in 172 patients, major cardiovascular events occurred in no patient, but TIMI bleeding events in 81 (47.09%) with major bleedings in three patients. All patients with major bleedings were classified as LTPR. Ticagrelor related dyspnea occurred in 31 (18.02%) patients, with 30 (21.28%) classified as LTPR and no one as HTPR (P = 0.02). Conclusions In ticagrelor treated ACS patients, MAADP measured by TEG might be valuable for the prediction of major bleeding and ticagrelor related dyspnea

  8. Anti-platelet activity of erythro-(7S,8R)-7-acetoxy-3,4,3',5'-tetramethoxy-8-O-4'-neolignan from Myristica fragrans.

    PubMed

    Kang, Jung Won; Min, Byung-Sun; Lee, Jeong-Hyung

    2013-11-01

    Platelets play a critical role in pathogenesis of cardiovascular disorders and strokes. The inhibition of platelet function is beneficial for the treatment and prevention of these diseases. In this study, we investigated the anti-platelet activity of erythro-(7S,8R)-7-acetoxy-3,4,3',5'-tetramethoxy-8-O-4'-neolignan (EATN), a neolignan isolated from Myristica fragrans, using human platelets. EATN preferentially inhibited thrombin- and platelet-activating factor (PAF)-induced platelet aggregation without affecting platelet damage in a concentration-dependent manner with IC50 values of 3.2 ± 0.4 and 3.4 ± 0.3 μM, respectively. However, much higher concentrations of EATN were required to inhibit platelet aggregation induced by arachidonic acid. EATN also inhibited thrombin-induced serotonin and ATP release, and thromboxane B2 formation in human platelets. Moreover, EATN caused an increase in cyclic AMP (cAMP) levels and attenuated intracellular Ca(2+) mobilization in thrombin-activated human platelets. Therefore, we conclude that the inhibitory mechanism of EATN on platelet aggregation may increase cAMP levels and subsequently inhibit intracellular Ca(2+) mobilization by interfering with a common signaling pathway rather than by directly inhibiting the binding of thrombin or PAF to their receptors. This is the first report of the anti-platelet activity of EATN isolated from M. fragrans. PMID:23296979

  9. Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect.

    PubMed

    Nadal, Jessica Mendes; Gomes, Mona Lisa Simionatto; Borsato, Débora Maria; Almeida, Martinha Antunes; Barboza, Fernanda Malaquias; Zawadzki, Sônia Faria; Kanunfre, Carla Cristine; Farago, Paulo Vitor; Zanin, Sandra Maria Warumby

    2016-07-01

    This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3μm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects. PMID:27127059

  10. Comparison of common platelet receptors between the chacma baboon (Papio ursinus) and human for use in pre-clinical human-targeted anti-platelet studies.

    PubMed

    Janse van Rensburg, Walter J

    2016-06-01

    Anti-platelet agents play a central part in the treatment and prevention of acute thrombotic events. Discriminating animal models are needed for the development of novel agents. The chacma baboon has been extensively used as a model to evaluate anti-platelet agents. However, limited data exist to prove the translatability of this species to humans. We aimed to determine the suitability of the chacma baboon in preclinical human targeted GPIIb/IIIa, GPIbα and P2Y12 studies. Light-transmission platelet aggregometry (LTA), whole blood impedance aggregometry, receptor number quantification and genomic DNA sequencing were performed. Baboon ADP and arachidonic acid-induced LTA aggregation results differed significantly from human values, even at increased concentrations. LTA ristocetin-induced agglutination was comparable between species, but baboon platelets needed twice the concentration of ristocetin to elicit a similar response. Citrated baboon blood had significantly less aggregation than humans when evaluated with impedance aggregometry. However, hirudinised baboon whole blood gave similar aggregation as humans at the same agonist concentrations. GPIIb, GPIIIa and GPIbα numbers were significantly more on the baboon platelets. None of the amino acids deemed vital for receptor function, ligand binding or receptor inhibition, were radically different between the species. However, a conservative change in a calcium-binding region of GPIIb may render the baboon platelets more sensitive to calcium-binding agents. The chacma baboon may be used for the evaluation of human-targeted GPIIb/IIIa-, GPIbα- and P2Y12-inhibiting agents. However, the best anticoagulant, optimal agonist concentrations, increase in receptor number and sequence differences must be considered for any future studies. PMID:26559117

  11. Statistical examination of laser therapy effects in controlled double-blind clinical trial

    NASA Astrophysics Data System (ADS)

    Boerner, Ewa; Podbielska, Halina

    2001-10-01

    For the evaluation of the therapy effects the double-blind clinical trial followed by statistical analysis was performed. After statistical calculations it was stated that laser therapy with IR radiation has a significant influence on the decrease of the level of pain in the examined group of patients suffering from various locomotive diseases. The level of pain of patients undergoing laser therapy was statistically lower than the level of pain of patients undergoing placebo therapy. It means that laser therapy had statistically significant influence on the decrease of the level of pain. The same tests were performed for evaluation of movement range. Although placebo therapy contributes to the increase of the range of movement, the statistically significant influence was stated in case of the therapeutic group treated by laser.

  12. Fluid Therapy: Double-Edged Sword during Critical Care?

    PubMed Central

    Benes, Jan; Kirov, Mikhail; Kuzkov, Vsevolod; Lainscak, Mitja; Molnar, Zsolt; Voga, Gorazd; Monnet, Xavier

    2015-01-01

    Fluid therapy is still the mainstay of acute care in patients with shock or cardiovascular compromise. However, our understanding of the critically ill pathophysiology has evolved significantly in recent years. The revelation of the glycocalyx layer and subsequent research has redefined the basics of fluids behavior in the circulation. Using less invasive hemodynamic monitoring tools enables us to assess the cardiovascular function in a dynamic perspective. This allows pinpointing even distinct changes induced by treatment, by postural changes, or by interorgan interactions in real time and enables individualized patient management. Regarding fluids as drugs of any other kind led to the need for precise indication, way of administration, and also assessment of side effects. We possess now the evidence that patient centered outcomes may be altered when incorrect time, dose, or type of fluids are administered. In this review, three major features of fluid therapy are discussed: the prediction of fluid responsiveness, potential harms induced by overzealous fluid administration, and finally the problem of protocol-led treatments and their timing. PMID:26798642

  13. A double pituitary adenoma presenting as a prolactin-secreting tumor with partial response to medical therapy. Case report.

    PubMed

    Coiré, Claire I; Smyth, Harley S; Rosso, Dominic; Horvath, Eva; Kovacs, Kalman

    2010-06-01

    Double pituitary adenomas are difficult to recognize pre-operatively as only a single mass may be appreciated on imaging. We present herein a giant prolactin-secreting pituitary adenoma in a middle-aged man that had responded partially to dopamine agonist therapy. The excised specimen demonstrated a double adenoma. The prolactin-producing one displayed the expected morphological changes resulting from medical therapy, while the other, a gonadotroph adenoma, did not. The failure of tumor shrinkage can be attributed to the presence of a double adenoma, a previously unreported cause of failure of medical therapy in prolactinoma. PMID:20058099

  14. Novel Microdilution Method to Assess Double and Triple Antibiotic Combination Therapy In Vitro

    PubMed Central

    El-Azizi, Mohamed

    2016-01-01

    An in vitro microdilution method was developed to assess double and triple combinations of antibiotics. Five antibiotics including ciprofloxacin, amikacin, ceftazidime, piperacillin, and imipenem were tested against 10 clinical isolates of Pseudomonas aeruginosa. Each isolate was tested against ten double and nine triple combinations of the antibiotics. A 96-well plate was used to test three antibiotics, each one alone and in double and triple combinations against each isolate. The minimum bacteriostatic and bactericidal concentrations in combination were determined with respect to the most potent antibiotic. An Interaction Code (IC) was generated for each combination, where a numerical value was designated based on the 2-fold increase or decrease in the MICs with respect to the most potent antibiotic. The results of the combinations were verified by time-kill assay at constant concentrations of the antibiotics and in a chemostat. Only 13% of the double combinations were synergistic, whereas 5% showed antagonism. Forty-three percent of the triple combinations were synergistic with no antagonism observed, and 100% synergism was observed in combination of ciprofloxacin, amikacin, and ceftazidime. The presented protocol is simple and fast and can help the clinicians in the early selection of the effective antibiotic therapy for treatment of severe infections. PMID:27195009

  15. cDNA cloning of a snake venom metalloproteinase from the eastern diamondback rattlesnake (Crotalus adamanteus), and the expression of its disintegrin domain with anti-platelet effects

    PubMed Central

    Suntravat, Montamas; Jia, Ying; Lucena, Sara E.; Sánchez, Elda E.; Pérez, John C.

    2013-01-01

    A 5′ truncated snake venom metalloproteinase was identified from a cDNA library constructed from venom glands of an eastern diamondback rattlesnake (Crotalus adamanteus). The 5′-rapid amplification of cDNA ends (RACE) was used to obtain the 1865 bp full-length cDNA sequence of a snake venom metalloproteinase (CamVMPII). CamVMPII encodes an open reading frame of 488 amino acids, which includes a signal peptide, a pro-domain, a metalloproteinase domain, a spacer, and an RGD-disintegrin domain. The predicted amino acid sequence of CamVMPII showed a 91%, 90%, 83%, and 82% sequence homology to the P-II class enzymes of C. adamanteus metalloproteinase 2, C. atrox CaVMP-II, Gloydius halys agkistin, and Protobothrops jerdonii jerdonitin, respectively. Disintegrins are potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion. Therefore, the disintegrin domain (Cam-dis) of CamVMPII was amplified by PCR, cloned into a pET-43.1a vector, and expressed in Escherichia coli BL21. Affinity purified recombinantly modified Cam-dis (r-Cam-dis) with a yield of 8.5 mg/L culture medium was cleaved from the fusion tags by enterokinase cleavage. r-Cam-dis was further purified by two-step chromatography consisting of HiTrap™ Benzamidine FF column, followed by Talon Metal affinity column with a final yield of 1 mg/L culture. r-Cam-dis was able to inhibit all three processes of platelet thrombus formation including platelet adhesion with an estimated IC50 of 1 nM, collagen- and ADP-induced platelet aggregation with the estimated IC50s of 18 and 6 nM, respectively, and platelet function on clot retraction. It is a potent anti-platelet inhibitor, which should be further investigated for drug discovery to treat stroke patients or patients with thrombotic disorders. PMID:23313448

  16. Non-Carriers of Reduced-Function CYP2C19 Alleles are Most Susceptible to Impairment of the Anti-Platelet Effect of Clopidogrel by Proton-Pump Inhibitors: A Pilot Study

    PubMed Central

    Lee, Jen-Kuang; Wu, Cho-Kai; Juang, Jyh-Ming; Tsai, Chia-Ti; Hwang, Juey-Jen; Lin, Jiuun-Lee; Chiang, Fu-Tien

    2016-01-01

    Background The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and proton-pump inhibitors (PPI). However, concomitant use of both drugs may reduce the desired therapeutic effects. In this study, we evaluated whether individuals with different numbers of reduced-function CYP2C19 alleles were equally affected and whether PPIs with different dependencies on CYP2C19 metabolism were equally involved. Methods Thirty healthy volunteers were recruited to a six-week regimen of clopidogrel. Three PPIs with different metabolic dependencies on CYP2C19 were included and separately administered in this order. Each PPI was given for a week, followed by a one-week washout period before the intervention of the next PPI. The anti-platelet effect was examined by Thromboelastography Platelet MappingTM (TEG®) and vasodilator-stimulated phosphoprotein (VASP) assays. Results Both TEG® and VASP tests showed the same general qualitative trend, but TEG® detected a statistically significant fluctuation of platelet aggregation in response to different drug interventions. The TEG® results also demonstrated that non-carriers experienced the most significant impairment of anti-platelet effect of clopidogrel after concomitant use of PPIs. This impairment was closely related to the metabolic dependence on CYP2C19 of PPI. Conclusions Our study indicated that non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel after concomitant PPI use. Individual subjects are not equally affected, and PPIs are not equally involved. However, large-scale randomized clinical trials are needed to evaluate the clinical outcome. PMID:27122952

  17. Reiki therapy for postoperative oral pain in pediatric patients: Pilot data from a double-blind, randomized clinical trial

    PubMed Central

    Kundu, Anjana; Lin, Yuting; Oron, Assaf P.; Doorenbos, Ardith Z.

    2014-01-01

    Purpose To examine the effects of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. Methods This was a double-blind, randomized controlled study of children undergoing dental procedures. Participants were randomly assigned to receive either Reiki therapy or the control therapy (sham Reiki) preoperatively. Postoperative pain scores, opioid requirements, and side effects were assessed. Family members were also asked about perioperative care satisfaction. Multiple linear regressions were used for analysis. Results Thirty-eight children participated. The blinding procedure was successful. No statistically significant difference was observed between groups on all outcome measures. Implications Our study provides a successful example of a blinding procedure for Reiki therapy among children in the perioperative period. This study does not support the effectiveness of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. PMID:24439640

  18. Managing tissue heating in laser therapy to enable double-blind clinical study

    NASA Astrophysics Data System (ADS)

    Catanzaro, Brian; de Taboada, Luis; Streeter, Jackson

    2006-02-01

    Laser devices in clinical applications must eventually be tested via clinical trials. An essential component in clinical trials is the double-blind study whereby the patient and the treating physician have no knowledge as to whether a given treatment is active or placebo. In pharmaceuticals, the problem is easily addressed. With laser therapy this can be very challenging. For some optical therapies, laser heating of tissue, by even as little as a few degrees can indicate to the patient and/or the physician that the device is active, un-blinding the study. This problem has been analyzed for a specific laser therapy using a combination of clinical data, analytical methods, finite element modeling, and laboratory testing. The methods used arrived at a solution, but not necessarily one that could have been predicted easily. This paper will present a model of tissue heating and the methods used to mask the effects from the laser in an effort to make active treatment and placebo indistinguishable.

  19. Static magnetic therapy does not decrease pain or opioid requirements: a randomized double-blind trial.

    PubMed

    Cepeda, M Soledad; Carr, Daniel B; Sarquis, Tony; Miranda, Nelcy; Garcia, Ricardo J; Zarate, Camilo

    2007-02-01

    A growing multibillion dollar industry markets magnetic necklaces, bracelets, bands, insoles, back braces, mattresses, etc., for pain relief, although there is little evidence for their efficacy. We sought to evaluate the effect of magnetic therapy on pain intensity and opioid requirements in patients with postoperative pain. We designed a randomized, double-blind, controlled trial. One-hundred-sixty-five patients older than 12 yr of age were randomized to magnetic (n = 81) or sham therapy (n = 84) upon reporting moderate-to-severe pain in the postanesthesia care unit. Devices were placed over the surgical incision and left in place for 2 h. Patients rated their pain intensity on a 0-10 scale every 10 min and received incremental doses of morphine until pain intensity was < or =4 of 10. Pain intensity levels were similar in both groups. The magnet group had on average 0.04 U more pain intensity (95% confidence interval, -0.4 to 0.5) than the sham group. Opioid requirements also were similar in both groups. The active magnet group required 1.5 mg more morphine (95% confidence interval, -1.8 to 4.0) than the sham magnet group. Magnetic therapy lacks efficacy in controlling acute postoperative pain intensity levels or opioid requirements and should not be recommended for pain relief in this setting. PMID:17242082

  20. Evaluation of E1A Double Mutant Oncolytic Adenovectors in Anti-Glioma Gene Therapy

    PubMed Central

    Ulasov, Ilya V.; Tyler, Matthew A.; Rivera, Angel A.; Nettelbeck, Dirk M.; Douglas, Joanne T.; Lesniak, Maciej S.

    2008-01-01

    Malignant glioma, in particular glioblastoma multiforme (GBM), represents one of the most devastating cancers currently known and existing treatment regimens do little to change patient prognosis. Conditionally replicating adenoviral vectors (CRAds) represent attractive experimental anti-cancer agents with potential for clinical application. However, early protein products of the wild type adenovirus backbone—such as E1A—limit CRAds’ replicative specificity. In this study, we evaluated the oncolytic potency and specificity of CRAds in which p300/CPB and/or pRb binding capacities of E1A were ablated to reduce non-specific replicative cytolysis. In vitro cytopathic assays, quantitative PCR analysis, Western blot, and flow cytometry studies demonstrate the superior anti-glioma efficacy of a double-mutated CRAd, Ad2/24CMV, which harbors mutations that reduce E1A binding to p300/CPB and pRb. When compared to its single-mutated and wild type counterparts, Ad2/24CMV demonstrated attenuated replication and cytotoxicity in representative normal human brain while displaying enhanced replicative cytotoxicity in malignant glioma. These results have implications for the development of double-mutated CRAd vectors for enhanced GBM therapy. PMID:18649343

  1. Combined chemotherapy and photodynamic therapy using a nanohybrid based on layered double hydroxides to conquer cisplatin resistance.

    PubMed

    Wang, Zhigang; Ma, Rong; Yan, Li; Chen, Xianfeng; Zhu, Guangyu

    2015-07-25

    A nanohybrid is assembled by ratiometrically co-loading Pt(IV) prodrugs and photosensitizers into layered double hydroxide nanoparticles. The nanohybrid shows synergistic cell-killing effects and is significantly active against the proliferation of cisplatin-resistant human cancer cells with nanomolar IC50 values. Profound mechanistic investigations confirm its action mode of combined chemo- and photodynamic therapy. PMID:26096645

  2. Crossover, double-blind clinical trial comparing almotriptan and ergotamine plus caffeine for acute migraine therapy.

    PubMed

    Láinez, M J A; Galván, J; Heras, J; Vila, C

    2007-03-01

    In this randomized, double-blind, crossover clinical trial, adult patients treated two migraine attacks: one with almotriptan 12.5 mg and the other with ergotamine 2 mg plus caffeine 200 mg. Treatment with almotriptan was associated with a significantly greater proportion of patients achieving 2-h pain free (20.9% vs. 13.7%; P < 0.05) and 2-h pain relief (57.7% vs. 44.5%; P < 0.01) compared with ergotamine plus caffeine therapy; significant differences were not seen at 1 h. Rates for sustained pain free and sustained pain free plus no adverse events (AEs) also were significantly greater after almotriptan treatment than after the use of ergotamine plus caffeine (P < 0.05). Almotriptan was associated with a significantly lower rate of photophobia at 90 min (P < 0.05), phonophobia at 60, 90, and 120 min (P < 0.05 to <0.01), and nausea and vomiting at 90 and 120 min (P < 0.01) compared with ergotamine plus caffeine. A significantly greater proportion of patients were more satisfied with almotriptan than with ergotamine plus caffeine (P < 0.05). Sixteen patients reported adverse events during almotriptan treatment and 27 patients reported AEs during the ergotamine plus caffeine therapy. Most AEs were mild-to-moderate and did not result in treatment-related discontinuations. In conclusion, almotriptan was associated with significantly greater efficacy for treating migraine compared with ergotamine plus caffeine, was generally well tolerated and was associated with greater rate of treatment satisfaction. PMID:17355546

  3. Lansoprazole for long-term maintenance therapy of erosive esophagitis: double-blind comparison with ranitidine.

    PubMed

    Peura, David A; Freston, James W; Haber, Marian M; Kovacs, Thomas O; Hunt, Barbara; Atkinson, Stuart

    2009-05-01

    In a study evaluating the efficacy and safety of lansoprazole to prevent the relapse of erosive esophagitis (EE), 206 of 241 patients (85%) healed after open-label treatment with lansoprazole 30 mg once daily for 8 weeks and received double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily for up to 1 year. At 1 year, 67% of lansoprazole-treated and 13% of ranitidine-treated patients remained healed (P<0.001). Lansoprazole-treated patients experienced significantly greater symptom relief (P<0.001), and, if asymptomatic at entry into the maintenance phase, remained asymptomatic for significantly longer than ranitidine-treated patients (P<0.001). Symptom status correlated with healing (P=0.001), supporting the symptom-directed management of EE. Both treatments were well tolerated and no unexpected events occurred. Daily therapy with lansoprazole to prevent the relapse of EE is effective, well tolerated, and superior to ranitidine in the maintenance of healing and symptom relief. PMID:18726153

  4. Double-Blinding and Bias in Medication and Cognitive-Behavioral Therapy Trials for Major Depressive Disorder

    PubMed Central

    Berger, Douglas

    2016-01-01

    While double-blinding is a crucial aspect of study design in an interventional clinical trial of medication for a disorder with subjective endpoints such as major depressive disorder, psychotherapy clinical trials, particularly cognitive-behavioral therapy trials, cannot be double-blinded. This paper highlights the evidence-based medicine problem of double-blinding in the outcome research of a psychotherapy and opines that psychotherapy clinical trials should be called, “partially-controlled clinical data” because they are not double-blinded. The implications for practice are, 1. For practitioners to be clear with patients the level of rigor to which interventions have been studied, 2. For authors of psychotherapy outcome studies to be clear that the problem in the inability to blind a psychotherapy trial severely restricts the validity of any conclusions that can be drawn, and 3. To petition National Health Insurance plans to use caution in approving interventions studied without double-blinded confirmatory trials as they may lead patients to avoid other treatments shown to be effective in double-blinded trials. PMID:26870318

  5. Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind placebo-controlled trial

    PubMed Central

    Rangaka, Molebogeng X; Wilkinson, Robert J; Boulle, Andrew; Glynn, Judith R; Fielding, Katherine; van Cutsem, Gilles; Wilkinson, Katalin A; Goliath, Rene; Mathee, Shaheed; Goemaere, Eric; Maartens, Gary

    2014-01-01

    Background Antiretroviral therapy (ART) reduces the risk of tuberculosis, but the incidence still exceeds that in HIV-uninfected people. Isoniazid preventive therapy (IPT), which decreases the risk of tuberculosis in people not on ART, may offer additional protection. Methods Pragmatic randomized double-blind placebo-controlled trial to evaluate the effect of 12 months IPT among participants established on or newly starting ART, in Khayelitsha, South Africa (NCT00463086, Lancet D-09-02885). Tuberculosis was excluded at screening by sputum culture. Incident tuberculosis was the primary endpoint. Findings 1,329 participants contributed 3,227 person-years (PY) of follow up in the modified intention-to-treat analysis; 662 on IPT and 667 on placebo. There were 95 incident tuberculosis cases: 2.3 (95%CI 1.6-3.1) versus 3.6 (95%CI 2.8-4.7) per 100 PY in the IPT and placebo arms respectively (hazard ratio 0.63, 95%CI 0.41-0.94). Study drug was discontinued due to grade 3 or 4 raised ALT in 19/662 in the IPT and 10/667 in the placebo arm, risk ratio=1.9 (95%CI 0.90-4.09). In secondary analyses, there was no evidence that the effect of IPT was restricted to those who were positive on tuberculin skin test (TST) or interferon gamma release assay (IGRA): adjusted hazard ratio for those with negative tests 0.43 (95%CI 0.21-0.86) and 0.43 (95%CI 0.20-0.96); for positive tests 0.86 (95%CI 0.37-2.00) and 0.55 (95%CI 0.26-1.24) respectively. No all cause mortality benefit of IPT was demonstrated Interpretation IPT reduced the incidence of tuberculosis in HIV-infected individuals on ART. In this high incidence setting, individuals on ART who have TST or IGRA negative results may also benefit from IPT. IPT can easily be implemented in ART clinics. PMID:24835842

  6. Double-blind, placebo-controlled study of HGF gene therapy in diabetic neuropathy

    PubMed Central

    Kessler, John A; Smith, A Gordon; Cha, Bong-Soo; Choi, Sung Hee; Wymer, James; Shaibani, Aziz; Ajroud-Driss, Senda; Vinik, Aaron

    2015-01-01

    Objective To evaluate the safety and efficacy of a plasmid (VM202) containing two human hepatocyte growth factor isoforms given by intramuscular injections in patients with painful diabetic neuropathy. Methods In a double-blind, placebo-controlled study, patients were randomized to receive injections of 8 or 16 mg VM202 per leg or placebo. Divided doses were administered on Day 0 and Day 14. The prospective primary outcome was change in the mean pain score measured by a 7 day pain diary. Secondary outcomes included a responder analysis, quality of life and pain measures, and intraepidermal nerve fiber density. Results There were no significant adverse events attributable to VM202. Eighty-four patients completed the study. Patients receiving 8 mg VM202 per leg improved the most in all efficacy measures including a significant (P = 0.03) reduction at 3 months in the mean pain score and continued but not statistically significant reductions in pain at 6 and 9 months. Of these patients, 48.4% experienced a ≥50% reduction in pain compared to 17.6% of placebo patients. There were also significant improvements in the brief pain inventory for patients with diabetic peripheral neuropathy and the questionnaire portion of the Michigan Neuropathy Screening Instrument. Patients not on pregabalin or gabapentin had the largest reductions in pain. Interpretation VM202 was safe, well tolerated and effective indicating the feasibility of a nonviral gene therapy approach to painful diabetic neuropathy. Two days of treatment were sufficient to provide symptomatic relief with improvement in quality of life for 3 months. VM202 may be particularly beneficial for patients not taking gabapentin or pregabalin. PMID:26000320

  7. Fast Pencil Beam Dose Calculation for Proton Therapy Using a Double-Gaussian Beam Model

    PubMed Central

    da Silva, Joakim; Ansorge, Richard; Jena, Rajesh

    2015-01-01

    The highly conformal dose distributions produced by scanned proton pencil beams (PBs) are more sensitive to motion and anatomical changes than those produced by conventional radiotherapy. The ability to calculate the dose in real-time as it is being delivered would enable, for example, online dose monitoring, and is therefore highly desirable. We have previously described an implementation of a PB algorithm running on graphics processing units (GPUs) intended specifically for online dose calculation. Here, we present an extension to the dose calculation engine employing a double-Gaussian beam model to better account for the low-dose halo. To the best of our knowledge, it is the first such PB algorithm for proton therapy running on a GPU. We employ two different parameterizations for the halo dose, one describing the distribution of secondary particles from nuclear interactions found in the literature and one relying on directly fitting the model to Monte Carlo simulations of PBs in water. Despite the large width of the halo contribution, we show how in either case the second Gaussian can be included while prolonging the calculation of the investigated plans by no more than 16%, or the calculation of the most time-consuming energy layers by about 25%. Furthermore, the calculation time is relatively unaffected by the parameterization used, which suggests that these results should hold also for different systems. Finally, since the implementation is based on an algorithm employed by a commercial treatment planning system, it is expected that with adequate tuning, it should be able to reproduce the halo dose from a general beam line with sufficient accuracy. PMID:26734567

  8. Fast Pencil Beam Dose Calculation for Proton Therapy Using a Double-Gaussian Beam Model.

    PubMed

    da Silva, Joakim; Ansorge, Richard; Jena, Rajesh

    2015-01-01

    The highly conformal dose distributions produced by scanned proton pencil beams (PBs) are more sensitive to motion and anatomical changes than those produced by conventional radiotherapy. The ability to calculate the dose in real-time as it is being delivered would enable, for example, online dose monitoring, and is therefore highly desirable. We have previously described an implementation of a PB algorithm running on graphics processing units (GPUs) intended specifically for online dose calculation. Here, we present an extension to the dose calculation engine employing a double-Gaussian beam model to better account for the low-dose halo. To the best of our knowledge, it is the first such PB algorithm for proton therapy running on a GPU. We employ two different parameterizations for the halo dose, one describing the distribution of secondary particles from nuclear interactions found in the literature and one relying on directly fitting the model to Monte Carlo simulations of PBs in water. Despite the large width of the halo contribution, we show how in either case the second Gaussian can be included while prolonging the calculation of the investigated plans by no more than 16%, or the calculation of the most time-consuming energy layers by about 25%. Furthermore, the calculation time is relatively unaffected by the parameterization used, which suggests that these results should hold also for different systems. Finally, since the implementation is based on an algorithm employed by a commercial treatment planning system, it is expected that with adequate tuning, it should be able to reproduce the halo dose from a general beam line with sufficient accuracy. PMID:26734567

  9. Plateletworks: A screening assay for clopidogrel therapy monitoring in healthy cats

    PubMed Central

    Hamel-Jolette, Avril; Dunn, Marilyn; Bédard, Christian

    2009-01-01

    Plateletworks is a screening assay used in human medicine to monitor platelet-inhibiting drugs. As arterial thromboembolism is a common complication in cats suffering from cardiomyopathy, they are often treated with anti-platelet medication. Clopidogrel (Plavix), an anti-platelet aggregation drug, has recently been evaluated in healthy cats. The purpose of this study was to determine if the Plateletworks method can detect a decrease in platelet aggregation in cats receiving clopidogrel. Nine healthy adult cats were used for this study. Platelet aggregation was measured before and after a 3-day clopidogrel treatment (18.75 mg SID). Platelet aggregation after the clopidogrel treatment was significantly lower (P < 0.01). The Plateletworks method appears to be a promising test to monitor clopidogrel therapy in cats. PMID:19337399

  10. A new analytical formula for neutron capture gamma dose calculations in double-bend mazes in radiation therapy

    PubMed Central

    Ghiasi, Hosein; Mesbahi, Asghar

    2012-01-01

    Background Photoneutrons are produced in radiation therapy with high energy photons. Also, capture gamma rays are the byproduct of neutrons interactions with wall material of radiotherapy rooms. Aim In the current study an analytical formula was proposed for capture gamma dose calculations in double bend mazes in radiation therapy rooms. Materials and methods A total of 40 different layouts with double-bend mazes and a 18 MeV photon beam of Varian 2100 Clinac were simulated using MCNPX Monte Carlo (MC) code. Neutron capture gamma ray dose equivalent was calculated by the MC method along the maze and at the maze entrance door of all the simulated rooms. Then, all MC resulted data were fitted to an empirical formula for capture gamma dose calculations. Wu–McGinley analytical formula for capture gamma dose equivalent at the maze entrance door in single-bend mazes was also used for comparison purposes. Results For capture gamma dose equivalents at the maze entrance door, the difference of 2–11% was seen between MC and the derived equation, while the difference of 36–87% was found between MC and the Wu–McGinley methods. Conclusion Our results showed that the derived formula results were consistent with the MC results for all of 40 different geometries. However, as a new formula, further evaluations are required to validate its use in practical situations. Finally, its application is recommend for capture gamma dose calculations in double-bend mazes to improve shielding calculations. PMID:24377027

  11. NOSH-sulindac (AVT-18A) is a novel nitric oxide- and hydrogen sulfide-releasing hybrid that is gastrointestinal safe and has potent anti-inflammatory, analgesic, antipyretic, anti-platelet, and anti-cancer properties

    PubMed Central

    Kashfi, Khosrow; Chattopadhyay, Mitali; Kodela, Ravinder

    2015-01-01

    Sulindac is chemopreventive and has utility in patients with familial adenomatous polyposis; however, side effects preclude its long-term use. NOSH-sulindac (AVT-18A) releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and anti-cancer properties of sulindac and NOSH-sulindac administered orally to rats at equimolar doses. Gastrointestinal safety: 6 h post-administration, number/size of hemorrhagic lesions in stomachs were counted. Tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1 h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5 h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5 h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Anti-cancer: We examined the effects of NOSH-sulindac on the growth properties of 12 human cancer cell lines of six different tissue origins. Both agents reduced PGE2 levels in stomach tissue; however, NOSH-sulindac did not cause any stomach ulcers, whereas sulindac caused significant bleeding. Lipid peroxidation induced by sulindac was higher than that from NOSH-sulindac. SOD activity was significantly lowered by sulindac but increased by NOSH-sulindac. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Sulindac increased plasma TNFα whereas this rise was lower in the NOSH-sulindac-treated animals. NOSH-sulindac inhibited the growth of all cancer cell lines studied, with potencies of 1000- to 9000-fold greater than that of sulindac. NOSH-sulindac inhibited cell proliferation, induced apoptosis, and caused G2/M

  12. Ertapenem-Containing Double-Carbapenem Therapy for Treatment of Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae

    PubMed Central

    Cprek, Jessica B.

    2015-01-01

    We describe outcomes of patients with infections with carbapenem-resistant Klebsiella pneumoniae (CRKP) who received ertapenem-containing double-carbapenem therapy (ECDCT). Clinical success was observed in 7/18 (39%) patients overall: bloodstream infections, 3/7 (43%); pneumonia, 1/5 (20%); intraabdominal infections, 0/2 (0%); urinary tract infections, 2/3 (67%); and a skin and skin structure infection, 1/1 (100%). Microbiologic success was observed in 11/14 (79%) evaluable patients; 5/18 (28%) patients died. ECDCT may be effective for CRKP infections with limited treatment options. PMID:26552970

  13. Epigenetic Modifications and Accumulation of DNA Double-Strand Breaks in Oral Lichen Planus Lesions Presenting Poor Response to Therapy.

    PubMed

    Dillenburg, Caroline S; Martins, Marco A T; Almeida, Luciana O; Meurer, Luise; Squarize, Cristiane H; Martins, Manoela D; Castilho, Rogerio M

    2015-07-01

    Epigenetics refers to changes in cell characteristics that occur independently of modifications to the deoxyribonucleic acid (DNA) sequence. Alterations mediated by epigenetic mechanisms are important factors in cancer progression. Although an exciting prospect, the identification of early epigenetic markers associated with clinical outcome in premalignant and malignant disorders remains elusive. We examined alterations in chromatin acetylation in oral lichen planus (OLP) with distinct clinical behavior and compared the alterations to the levels of DNA double-strand breaks (DSBs). We analyzed 42 OLP patients, who had different responses to therapy, for acetyl-histone H3 at lys9 (H3K9ac), which is associated with enhanced transcription and nuclear decondensation, and the presence of DSBs, as determined by accumulation of phosphorylated γH2AX foci. Patients with high levels of H3K9ac acetylation failed to respond to therapy or experienced disease recurrence shortly after therapy. Similar to H3K9ac, patients who responded poorly to therapy had increased accumulation of DNA DSB, indicating genomic instability. These findings suggest that histone modifications occur in OLP, and H3K9ac and γH2AX histones may serve as epigenetic markers for OLP recurrence. PMID:26222871

  14. BEMER Therapy Combined with Physiotherapy in Patients with Musculoskeletal Diseases: A Randomised, Controlled Double Blind Follow-Up Pilot Study

    PubMed Central

    Gyulai, Franciska; Rába, Katalin; Baranyai, Ildikó; Berkes, Enikő; Bender, Tamás

    2015-01-01

    Background. This study evaluates the effect of adjuvant BEMER therapy in patients with knee arthrosis and chronic low back pain in a randomized double blind design. Methods. A total of 50 patients with chronic low back pain and 50 patients with osteoarthritis of knee took part in this study and were randomized into 4 groups. Hospitalized patients received a standardized physiotherapy package for 3 weeks followed by BEMER therapy or placebo. Results. In patients with low back pain, the comparison of the results obtained at the first and second visit showed a significant improvement in resting VAS scores and Fatigue Scale scores. The Oswestry scores and Quality of Life Scale scores showed no change. In patients with knee arthrosis, the comparison of the first and second measurements showed no significant improvement in the abovementioned parameters, while the comparison of the first and third scores revealed a significant improvement in the Fatigue Scale scores and in the vitality test on the Quality of Life Scale. Conclusions. Our study showed that BEMER physical vascular therapy reduced pain and fatigue in the short term in patients with chronic low back pain, while long-term therapy appears to be beneficial in patients with osteoarthritis of knee. PMID:26078768

  15. BEMER Therapy Combined with Physiotherapy in Patients with Musculoskeletal Diseases: A Randomised, Controlled Double Blind Follow-Up Pilot Study.

    PubMed

    Gyulai, Franciska; Rába, Katalin; Baranyai, Ildikó; Berkes, Enikő; Bender, Tamás

    2015-01-01

    Background. This study evaluates the effect of adjuvant BEMER therapy in patients with knee arthrosis and chronic low back pain in a randomized double blind design. Methods. A total of 50 patients with chronic low back pain and 50 patients with osteoarthritis of knee took part in this study and were randomized into 4 groups. Hospitalized patients received a standardized physiotherapy package for 3 weeks followed by BEMER therapy or placebo. Results. In patients with low back pain, the comparison of the results obtained at the first and second visit showed a significant improvement in resting VAS scores and Fatigue Scale scores. The Oswestry scores and Quality of Life Scale scores showed no change. In patients with knee arthrosis, the comparison of the first and second measurements showed no significant improvement in the abovementioned parameters, while the comparison of the first and third scores revealed a significant improvement in the Fatigue Scale scores and in the vitality test on the Quality of Life Scale. Conclusions. Our study showed that BEMER physical vascular therapy reduced pain and fatigue in the short term in patients with chronic low back pain, while long-term therapy appears to be beneficial in patients with osteoarthritis of knee. PMID:26078768

  16. Epigenetic Modifications and Accumulation of DNA Double-Strand Breaks in Oral Lichen Planus Lesions Presenting Poor Response to Therapy

    PubMed Central

    Dillenburg, Caroline S.; Martins, Marco A.T.; Almeida, Luciana O.; Meurer, Luise; Squarize, Cristiane H.; Martins, Manoela D.; Castilho, Rogerio M.

    2015-01-01

    Abstract Epigenetics refers to changes in cell characteristics that occur independently of modifications to the deoxyribonucleic acid (DNA) sequence. Alterations mediated by epigenetic mechanisms are important factors in cancer progression. Although an exciting prospect, the identification of early epigenetic markers associated with clinical outcome in premalignant and malignant disorders remains elusive. We examined alterations in chromatin acetylation in oral lichen planus (OLP) with distinct clinical behavior and compared the alterations to the levels of DNA double-strand breaks (DSBs). We analyzed 42 OLP patients, who had different responses to therapy, for acetyl-histone H3 at lys9 (H3K9ac), which is associated with enhanced transcription and nuclear decondensation, and the presence of DSBs, as determined by accumulation of phosphorylated γH2AX foci. Patients with high levels of H3K9ac acetylation failed to respond to therapy or experienced disease recurrence shortly after therapy. Similar to H3K9ac, patients who responded poorly to therapy had increased accumulation of DNA DSB, indicating genomic instability. These findings suggest that histone modifications occur in OLP, and H3K9ac and γH2AX histones may serve as epigenetic markers for OLP recurrence. PMID:26222871

  17. Standard Triple Therapy versus Sequential Therapy in Helicobacter pylori Eradication: A Double-Blind, Randomized, and Controlled Trial

    PubMed Central

    Navarro-Rodriguez, Tomás; Teixeira, Ana Cristina Sá; Silva, Fernando Marcuz; Mattar, Rejane; Chinzon, Decio; Haro, Christiane; Moraes-Filho, Joaquim Prado; Fass, Ronnie; Barbuti, Ricardo Correa

    2015-01-01

    Aim. To compare 10-day standard triple therapy versus sequential therapy as first-line treatment in patients infected with H. pylori. Methods. One hundred H. pylori positive patients (diagnosed by rapid urease test and histology), with average age of 47.2, M/F = 28/72, were randomized to receive either standard triple treatment (TT) as follows: lansoprazole 30 mg, clarithromycin 500 mg, and amoxicillin 1 g, b.i.d. for ten days, or sequential treatment (ST) as follows: lansoprazole 30 mg, amoxicillin and placebo 1.0 g b.i.d for the first five days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and tinidazole 500 mg b.i.d, for the remaining five days. Eradication rates were determined 60 days after treatment by urease, histology, or 13C-urea breath test. Results. In intention to treat (ITT) analysis, the rate of H. pylori eradication in the TT and ST groups was the same for both regimens as follows: 86% (43/50), 95% CI 93,3 to 73.4%. In Per protocol (PP) analysis, the rate of H. pylori eradication in the TT and ST groups was 87.8% (43/49), 95% CI 94,5 to 75.3% and 89.6% (43/48), 95% CI 95,8 to 77.3%, respectively. Conclusions. In Brazil, standard triple therapy is as equally effective as sequential therapy in eradicating Helicobacter pylori patients. This study was registered under Clinical Trials with number ISRCTN62400496. PMID:26064098

  18. Monodisperse double-walled microspheres loaded with chitosan-p53 nanoparticles and doxorubicin for combined gene therapy and chemotherapy

    PubMed Central

    Xu, Qingxing; Xia, Yujie; Wang, Chi-Hwa; Pack, Daniel W.

    2012-01-01

    We have designed and evaluated a dual anticancer delivery system to provide combined gene therapy and chemotherapy. Double-walled microspheres consisting of a poly(D,L-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(lactic acid) (PLA) shell were fabricated via the precision particle fabrication (PPF) technique. We make use of the advantages of double-walled microspheres to deliver chitosan-DNA nanoparticles containing the gene encoding the p53 tumor suppressor protein (chi-p53) and/or doxorubicin (Dox), loaded in the shell and core phases, respectively. Different molecular weights of PLA were used to form the shell layer for each formulation. The microspheres were monodisperse with a mean diameter of 65 to 75 μm and uniform shell thickness of 8 to 17 μm. Blank and Dox-loaded microspheres typically exhibited a smooth surface with relatively few small pores, while chi-microspheres containing p53 nanoparticles, with and without Dox, presented rough and porous surfaces. The encapsulation efficiency of Dox was significantly higher when it was encapsulated alone compared to co-encapsulation with chi-p53 nanoparticles. The encapsulation efficiency of chi-p53 nanoparticles, on the other hand, was not affected by the presence of Dox. As desired, chi-p53 nanoparticles were released first, followed by simultaneous release of chi-p53 nanoparticles and Dox at a near zero-order rate. Thus, we have demonstrated that the PPF method is capable of producing double-walled microspheres and encapsulating dual agents for combined modality treatment, such as gene therapy and chemotherapy. PMID:22981564

  19. Synergistic effect of anti-platelet and anti-inflammation of drug-coated Co-Cr substrates for prevention of initial in-stent restenosis.

    PubMed

    Lih, Eugene; Jung, Jee Won; Joung, Yoon Ki; Ahn, Dong June; Han, Dong Keun

    2016-04-01

    Antiplatelet and antithrombotic therapies are systematically considered to prevent restenosis following coronary stent implantation. Currently, patients receiving medicated stents are prescribed to orally take anticoagulants and antiplatelet drugs such as aspirin (ASP) and prasugrel (PRAS). Propolis (PROP) known as a natural organic compound was recently evaluated for its antiplatelet activity, antibiotics and immunomodulatory activities. In this study, antiplatelet drug-coated Co-Cr substrates were prepared with biodegradable poly(d,l-lactide) (PDLLA) containing ASP, PRA, or PROP using electrospray and the blood compatibility of the different substrates was investigated by measuring protein adsorption and platelet adhesion. In addition, the anti-inflammatory properties of the modified Co-Cr surfaces were assessed by measuring IL-8 and IL-6 expression levels in human endothelial cell cultures. Drug-coated surfaces were found to resist the adsorption of fibrinogen when compared to bare Co-Cr or PDLLA-coated Co-Cr. Interestingly, ASP- and PROP-containing substrates not only showed reduced adhesion of platelets and delayed coagulation time, but also drastically reduced the expression level of IL-8 and IL-6. Such results are supported that ASP- or PROP-coated Co-Cr can be potentially used as a stent material to mitigate early stage of restenosis. The developed coating materials might be an interesting alternative to systemic anticoagulant therapies prescribed after stent implantation. PMID:26774572

  20. Dutasteride in men receiving testosterone therapy: a randomised, double-blind study.

    PubMed

    Kacker, R; Harisaran, V; Given, L; Miner, M; Rittmaster, R; Morgentaler, A

    2015-03-01

    We investigate the impact of dutasteride on prostate specific antigen (PSA) and prostate volume in men receiving testosterone (T) therapy. Twenty-three men on stable dose T therapy were randomised to receive either dutasteride or placebo for 12 months. Serum levels of PSA, T and dihydrotestosterone (DHT) and responses to the International Index of Erectile Function (IIEF) and Male Sexual Health Questionnaire (MSHQ) questionnaires were determined at baseline and at 3, 6, 9 and 12 months. Prostate volume (PV) was measured using transrectal ultrasound (TRUS) at baseline and again after 12 months. A total of 22 men (mean age 57.3) completed the study, with 11 men receiving placebo and 11 receiving dutasteride. Men receiving dutasteride had a significant decrease in PSA (-0.46 ± 0.81 ng ml(-1) ; P = 0.04) and in PV (-6.65 ± 11.0%; P = 0.03) from baseline over 12 months. DHT decreased significantly for men on dutasteride compared with men receiving placebo (P = 0.02). When compared with men who received placebo, men who received dutasteride demonstrated nonsignificant trends towards decreased PSA (-0.46 versus 0.21 ng ml(-1) ; P = 0.11), PV (-6.65% versus 3.4%; P = 0.08) and MSHQ scores (-10.2 versus 5.6; P = 0.06). Dutasteride reduces PSA and PV for men on T therapy, but perhaps less so than in men without T therapy. PMID:24499051

  1. Monotherapy versus dual therapy for the initial treatment of hypertension (PATHWAY-1): a randomised double-blind controlled trial

    PubMed Central

    MacDonald, Thomas M; Williams, Bryan; Caulfield, Mark; Cruickshank, J Kennedy; McInnes, Gordon; Sever, Peter; Webb, David J; Mackenzie, Isla S; Salsbury, Jackie; Morant, Steve; Ford, Ian; Brown, Morris J

    2015-01-01

    Introduction Previous studies have suggested that more intensive initial therapy for hypertension results in better long-term blood pressure (BP) control. We test this hypothesis comparing initial monotherapy with dual therapy in the management of essential hypertension. Methods and analysis The study is a prospective, multicentre, double-blind, active-controlled trial in patients with essential hypertension. Around 50% of patients studied will be newly diagnosed and the others will be known hypertensives who previously received only monotherapy. The trial is divided into three phases as follows: Phase 1 (Week 0–Week 16): Randomised, parallel-group, masked assignation to either combination or monotherapy. Phase 2 (Week 17–Week 32): Open-label combination therapy. Phase 3 (Week 33–Week 52): Open-label combination therapy plus open-label add-on (if BP is above 140/90 mm Hg). Hierarchical primary end points are: a comparison of home BP (home systolic blood pressure (HSBP)) averaged over the duration of phase 1 and 2 in the combination versus monotherapy arms. If combination is superior in this analysis, then the averaged mean HSBP between initial monotherapy and initial combination therapy at the end of phase 2 will be compared. Secondary end points include: BP control at 1 year; the role of age, baseline renin, sodium status, plasma volume, haemodynamic compensation and peripheral resistance on BP control; validation of the National Institute for Clinical Excellence/British Hypertension Society joint guideline algorithm; safety and tolerability of combination therapy; and the impact of combination versus monotherapy on left ventricular mass and aortic pulse wave velocity. A sample size of 536 (268 in each group) will have 90% power to detect a difference in means of 4 mm Hg. Ethics and dissemination PATHWAY 1 was approved by UK ethics (REC Reference 09/H0308/132). Trial results will be published and all participating subjects will be informed of the

  2. Double-walled Au nanocage/SiO2 nanorattles: integrating SERS imaging, drug delivery and photothermal therapy.

    PubMed

    Hu, Feng; Zhang, Yan; Chen, Guangcun; Li, Chunyan; Wang, Qiangbin

    2015-02-25

    In this work, a novel type of nanomedical platform, the double-walled Au nanocage/SiO(2) nanorattle, is successfully fabricated by combining two "hollow-excavated strategies"--galvanic replacement and "surface-protected etching". The rational design of double-walled nanostructure based on gold nanocages (AuNCs) and hollow SiO(2) shells functionalized respectively with p-aminothiophenol (pATP) and Tat peptide simultaneously renders the nanoplatforms three functionalities: 1) the whole nanorattle serves as a high efficient drug carrier thanks to the structural characteristics of AuNC and SiO(2) shell with hollow interiors and porous walls; 2) the AuNC with large electromagnetic enhancement acts as a sensitive surface-enhanced Raman scattering (SERS) substrate to track the internalization process of the nanorattles by human MCF-7 breast cancer cells, as well as an efficient photothermal transducer for localized hyperthermia cancer therapy due to the strong near-infrared absorption; 3) Tat-functionalized SiO(2) shell not only improves biocompatibility and cell uptake efficiency resulting in enhanced anticancer efficacy but also prevents the AuNCs from aggregation and provides the stability of AuNCs so that the SERS signals can be used for cell tracking in high fidelity. The reported chemistry and the designed nanostructures should inspire more interesting nanostructures and applications. PMID:25348096

  3. Most Recent Evidence Behind Aggregometry and Genotyping Methods as Platelet Function Testing for Tailored Anti-Platelet Treatment Among PCI Patients.

    PubMed

    Gajda, Sylwia N; Kołtowski, Łukasz; Tomaniak, Mariusz

    2015-01-01

    Aggregometry and genotyping are methods of platelet function testing, which can be beneficial for high-risk patients undergoing invasive cardiac procedures. An optimal level of platelet reactivity (PR) should be maintained. There are discrepancies between individuals and their response to clopidogrel, accounting for the incidence of poor responders from 5% to 44%. This phenomenon predisposes the patients to increased risk of ischaemic events and thereby overall poorer clinical outcome. Prasugrel and tricagrelor are newer without genetic correlation to their action, however associated with increased bleeding risk. Aggregometry methods assess platelet reactivity at the exact moment of blood sampling. They reflect "phenotype" of the patient and vary after drug administration or dose change. The most popular tests are Light Transmission Aggregometry, Vasodilator-Stimulated Protein, VerifyNow, Multiple Electrode Aggregometry and Thrombelastography. There is proven genetic correlation between some cytochrome enzymes on clopidogrel response. The most widely tested is gene CYP2C19, which produces the enzyme transforming clopidogrel into an active metabolite. The CYP2C19*2 allele carriers have higher PR which can result in more thrombotic events. The manuscript shows the most recent evidence behind platelet function testing. Aggregometry is shown to be beneficial in 5 trials and 1 meta-analysis, while one paper was of different opinion. Ten studies show a positive clinical effect of genotyping on patients' outcome, while one does not support it. The best method of identifying high-risk individuals could be both methods and personalisation of antiplatelet therapy may decrease adverse ischaemic outcomes. PMID:26469115

  4. Home therapy with LMWH in deep vein thrombosis: randomized study comparing single and double daily administrations.

    PubMed

    Bellosta, Raffaello; Ferrari, Patrizio; Luzzani, Luca; Carugati, Claudio; Cossu, Luisa; Talarico, Matteo; Sarcina, Antonio

    2007-01-01

    The aim of this study was to assess the effectiveness of low-molecular-weight heparin (LMWH) treatment of deep vein thrombosis (DVT) in terms of the evolution of thrombosis, the incidence of adverse events, and compliance with heparin treatment using 2 types of LMWH available on the market administered in therapeutic doses throughout the period of treatment (Nadroparin) or at therapeutic doses only during the first month of treatment followed by a prophylactic phase at half dose (Parnaparin). A randomized prospective study was carried out on patients under observation with a recent diagnosis of DVT. The objectives of the study were to confirm the effectiveness of therapy with LMWH in terms of prevention of the risk of thromboembolism, of relapse of DVT, and of hemorrhagic complications, and to complete an evaluation of venous recanalization and residual valve competence in the 2 groups of patients. From December 2002 to June 2005, we randomized a total of 91 patients (51 in the Parnaparin group and 40 in the Nadroparin group). Overall, there was 1 case of nonfatal pulmonary embolism (1.1%) at 7 days into therapy with LMWH. There were 3 cases (3.3%) of progression of thrombosis despite therapy with LMWH, 2 cases (5%) in the Nadroparin group, and 1 case (2%) in the Parnaparin group (P = NS), and after suspension of the therapy, there was 1 case of relapse of thrombosis. Three of the 4 thrombotic events occurred in patients with active neoplasia. Moreover, only 1 major hemorrhagic event (1.1%) required blood transfusion. The Doppler ultrasound in the follow-up showed a complete resolution of 56% of the vein thromboses at an average of 6.1 +/- 4.6 (mean +/- SD) months. Valve competence recovered in 65.9% of cases with no significant difference between the 2 heparin groups. Home treatment of sural and femoral-popliteal DVT using LMWH represents a safe and effective method in the prevention of pulmonary embolism and encourages the process of recanalization of the

  5. Double-blind controlled randomised study of lactulose and lignin hydrolysed combination in complex therapy of atopic dermatitis

    PubMed Central

    Perlamutrov, Yuri N.; Olhovskaya, Kira B.; Zakirova, Svetlana A.

    2016-01-01

    Background Atopic dermatitis (AD) is an immune mediated disease with complex pathogenesis characterised by persistency, frequent exacerbations, and inefficacy of existing therapies. Damaged or weakened intestinal microbiocenosis is considered as an important aetiological factor of AD. The aim of this study was to evaluate the efficacy and safety of medical preparation Lactofiltrum (lactulose and sorbent (lignin hydrolysed)) in comparison with placebo in complex with standard therapy of AD. Methods Double-blind, placebo controlled, randomised comparative study of effectiveness and safety of 400 mg lactulose and 120 mg lignin hydrolysed combination as a part of standard combined AD treatment, conducted in parallel groups of patients aged 18–60. Results Comparison of clinical efficacy of Lactofiltrum in combination with the standard treatment has been demonstrated by measuring the following parameters: administration of Lactofiltrum results in 1) distinct clinical improvement in 56.75% of patients, 2) decrease of the mean values of scoring atopic dermatitis (SCORAD) index in 71.94% of patients, 3) elimination of itching in 50% of patients, and 4) life quality improvement for 76.41%. In the placebo group, 1) distinct clinical improvement was observed in 20% of patients, 2) decrease in SCORAD index values observed by 56.98%, 3) itching relief in 15.56%, and 4) life quality improvement by 36.38%. Conclusions Clinical improvement and persistent termination of clinical symptoms provide evidence of effectiveness in use of Lactofiltrum combined with the standard treatment of AD. PMID:27341938

  6. Double-edged sword of radiotherapy: a cause of secondary angiosarcoma after breast conservation therapy.

    PubMed

    Iqbal, Fahad Mujtaba; Ahmed, Balen; Vidya, Raghavan

    2016-01-01

    Angiosarcomas are rare and aggressive malignant tumours of vascular or endothelial origin that can originate in the breast. They can be classified as primary or secondary, with the latter most commonly due to postoperative radiotherapy as part of breast conservation therapy (wide local excision and adjuvant radiotherapy) for breast cancer. We report a case of postirradiation secondary angiosarcoma in a 56-year-old woman, alongside a review of the current literature, to inform clinicians of its clinical presentation and characteristics as a high index of clinical suspicion is required for an accurate diagnosis. PMID:27113794

  7. Concomitant therapy with Cineole (Eucalyptole) reduces exacerbations in COPD: A placebo-controlled double-blind trial

    PubMed Central

    Worth, Heinrich; Schacher, Christian; Dethlefsen, Uwe

    2009-01-01

    Background The clinical effects of mucolytics in patients with chronic obstructive pulmonary disease (COPD) are discussed controversially. Cineole is the main constituent of eucalyptus oil and mainly used in inflammatory airway diseases as a mucolytic agent. We hypothesised that its known mucolytic, bronchodilating and anti-inflammatory effects as concomitant therapy would reduce the exacerbation rate and show benefits on pulmonary function tests as well as quality of life in patients with COPD. Methods In this double-blind, placebo-controlled multi-center-study we randomly assigned 242 patients with stable COPD to receive 200 mg of cineole or placebo 3 times daily as concomitant therapy for 6 months during winter-time. The frequency, duration and severity of exacerbations were combined as primary outcome measures for testing as multiple criteria. Secondary outcome measures included changes of lung function, respiratory symptoms and quality of life as well as the single parameters of the exacerbations. Results Baseline demographics, lung function and standard medication of both groups were comparable. During the treatment period of 6 months the multiple criteria frequency, severity and duration of exacerbations were significantly lower in the group treated with cineole in comparison to placebo. Secondary outcome measures validated these findings. Improvement of lung function, dyspnea and quality of life as multiple criteria were statistically significant relative to placebo. Adverse events were comparable in both groups. Conclusion Concomitant therapy with cineole reduces exacerbations as well as dyspnea and improves lung function and health status. This study further suggests cineole as an active controller of airway inflammation in COPD by intervening in the pathophysiology of airway inflammation of the mucus membrane. Trial registration ISRCTN07600011 PMID:19624838

  8. In vivo vitiligo induction and therapy model: double-blind, randomized clinical trial.

    PubMed

    van Geel, Nanja; Speeckaert, Reinhart; Mollet, Ilse; De Schepper, Sofie; De Wolf, Julie; Tjin, Esther P M; Luiten, Rosalie M; Lambert, Jo; Brochez, Lieve

    2012-01-01

    In this study, we developed an in vivo vitiligo induction model to explore the underlying mechanisms leading to Koebner's phenomenon and to evaluate the efficacy of therapeutic strategies. The model consisted of 12 pigmented test regions on the back of generalized vitiligo patients that were exposed to three Koebner induction methods: cryotherapy, 755 nm laser therapy, and epidermal abrasion. In addition, four cream treatments (pimecrolimus, tacrolimus, steroid and placebo) were randomly applied. Koebnerization was efficiently induced by all three induction methods. In general, cryotherapy was the best method of Koebner induction, followed by 755 nm laser therapy and epidermal abrasion. Reproducible results were obtained, which showed enhanced depigmented surface areas and higher amounts of T lymphocytes in placebo-treated test zones compared to active treated areas. Tacrolimus and local steroids were better inhibitors of Koebner's process (P < 0.05) compared to pimecrolimus. Our in vivo vitiligo induction model is very informative to investigate vitiligo induction and to determine the efficacy of topical treatments in vitiligo. This proof of concept confirms the efficient comparison of head-to-head therapeutic strategies intra-individually in a standardized, specific and better timed way. PMID:21982055

  9. PSA doubling time kinetics during prostate cancer biochemical relapse after external beam radiation therapy

    SciTech Connect

    Bates, Andrew Tom . E-mail: andrew.bates@doctors.org.uk; Pickles, Tom; Paltiel, Chuck

    2005-05-01

    Purpose: To investigate whether prostate-specific antigen PSA doubling time (PSADT) is constant in men with biochemical prostate cancer relapse after external beam radiotherapy (EBRT). Methods and Materials: A total of 513 men treated radically with EBRT, with or without androgen ablation (AA), between 1993 and 2000, developed biochemical relapse. The slope of the ln (PSA) vs. time graph is calculated for the first two values after PSA nadir (first slope), the last two recorded PSAs (last slope), and all values excluding the first and final PSA (mid slope). Differences in these slopes were compared statistically with subgroup analysis for AA and secondary intervention. Results: For men treated with EBRT and AA first slope was faster than either mid slope (p = 0.031) or last slope (p < 0.001). Men treated with EBRT alone had no change in PSADT over time unless they subsequently received secondary intervention. This group had a more rapid last slope compared with mid slope (p < 0.001). Conclusions: PSA initially rises more rapidly after AA cessation, probably because of testosterone recovery. A subgroup of patients, who received secondary intervention after treatment with radiotherapy alone, showed a change in PSADT, to a faster velocity. This greater than constant exponential PSA growth is presumably the catalyst for secondary intervention. Otherwise, PSADT did not change during prostate cancer biochemical relapse.

  10. A pH-responsive layered double hydroxide (LDH)-phthalocyanine nanohybrid for efficient photodynamic therapy.

    PubMed

    Li, Xing-Shu; Ke, Mei-Rong; Huang, Wei; Ye, Chun-Hong; Huang, Jian-Dong

    2015-02-16

    A pH-responsive nanohybrid (LDH-ZnPcPS4 ), in which a highly hydrophilic zinc(II) phthalocyanine tetra-α-substituted with 4-sulfonatophenoxy groups (ZnPcPS4 ) is incorporated with a cationic layered double hydroxide (LDH) based on electrostatic interaction, has been specially designed and prepared through a facile co-precipitation approach. ZnPcPS4 is an excellent singlet-oxygen generator with strong absorption at the near-infrared region (692 nm) in cellular culture media, whereas the photoactivities of ZnPcPS4 were remarkably inhibited after incorporation with the LDH. The nanohybrid is essentially stable in aqueous media at pH 7.4; nevertheless, in slightly acidic media of pH 6.5 or 5.0, ZnPcPS4 can be efficiently released from the LDH matrix, thus leading to restoration of the photoactivities. The nanohybrid shows a high photocytotoxicity against HepG2 cells as a result of much more efficient cellular uptake and preferential accumulation in lysosomes, whereby the acidic environment leads to the release of ZnPcPS4 . The IC50 value of LDH-ZnPcPS4 is as low as 0.053 μM, which is 24-fold lower than that of ZnPcPS4 . This work provides a facile approach for the fabrication of photosensitizers with high photocytotoxicity, potential tumor selectivity, and rapid clearance character. PMID:25639348

  11. A double-regulated oncolytic adenovirus with improved safety for adenocarcinoma therapy

    SciTech Connect

    Wei, Na; Fan, Jun Kai; Gu, Jin Fa; He, Ling Feng; Tang, Wen Hao; Cao, Xin; Liu, Xin Yuan

    2009-10-16

    Safety and efficiency are equally important to be considered in developing oncolytic adenovirus. Previously, we have reported that ZD55, an oncolytic adenovirus with the deletion of E1B-55K gene, exhibited potent antitumor activity. In this study, to improve the safety of ZD55, we utilized MUC1 promoter to replace the native promoter of E1A on the basis of ZD55, and generated a double-regulated adenovirus, named MUD55. Our data demonstrated that the expression of early and late genes of MUD55 was both reduced in MUC1-negative cells, resulting in its stricter glandular-tumor selective progeny production. The cytopathic effect of MUD55 was about 10-fold lower than mono-regulated adenovirus ZD55 or Ad.MUC1 in normal cells and not obviously attenuated in glandular tumor cells. Moreover, MUD55 showed the least liver toxicity when administrated by intravenous injection in nude mice. These results indicate that MUD55 could be a promising candidate for the treatment of adenocarcinoma.

  12. Double umbilical cord blood transplant is effective therapy for relapsed or refractory Hodgkin lymphoma.

    PubMed

    Thompson, Philip A; Perera, Travis; Marin, David; Oran, Betul; Popat, Uday; Qazilbash, Muzaffar; Shah, Nina; Parmar, Simrit; Rezvani, Katayoun; Olson, Amanda; Kebriaei, Partow; Anderlini, Paolo; Rondon, Gabriela; Alousi, Amin; Ciurea, Stefan; Champlin, Richard E; Bajel, Ashish; Szer, Jeffrey; Shpall, Elizabeth J; Ritchie, David; Hosing, Chitra M

    2016-07-01

    A sub-group of patients with Hodgkin Lymphoma (HL) who relapse after autologous stem cell transplant can achieve long-term disease-free-survival after allogeneic stem cell transplant (alloSCT). There is limited information regarding the tolerability and efficacy of double umbilical cord blood transplant (dUCBT) for relapsed/refractory HL. We analyzed 27 consecutive, heavily pre-treated patients receiving dUCBT for relapsed/refractory HL at two centers from 2003-2014. The majority of patients relapsed <6 months after autologous stem cell transplant. A total of 15 patients received myeloablative (most commonly melphalan, fludarabine, thiotepa and anti-thymocyte globulin [ATG]) and 12 non-myeloablative conditioning regimens (fludarabine, cyclophosphamide, 200cGy total body irradiation +/- ATG). All patients engrafted; median time to neutrophil and platelet engraftment was 17 and 37 days, respectively. Overall response rate was 68%; 58% achieved complete remission. Median progression-free survival (PFS) was 12.2 months; median overall survival was 27 months. Cumulative incidences of relapse and of non-relapse mortality at 5 years were 30% and 37.9%, respectively; 5-year PFS was 31.3% (95%CI 10.1-52.5). There was a trend toward inferior PFS in patients with lymph node size ≥2 cm at the time of alloSCT (p = 0.07) and toward inferior survival in patients with chemorefractory disease pre-alloSCT (p = 0.12). dUCBT is feasible in patients with heavily pre-treated HL and can achieve long-term disease-free survival in approximately 30% of patients. PMID:26472485

  13. [Double-blind study of mianserin and fluoxetine in ambulatory therapy of depressed patients].

    PubMed

    Besançon, G; Cousin, R; Guitton, B; Lavergne, F

    1993-01-01

    A double blind controlled trial was carried out in 65 depressed out-patients to compare the efficacy and tolerance of mianserin with fluoxetine. The two compounds present very different pharmacological activities. Mianserin is an antagonist of the alpha 2-adrenergic receptors, while fluoxetine is an inhibitor of recapture specific to serotonin. Requirements for inclusion were: depressive episode of less than 2 months duration, meeting the criteria for one of the sub-types of depression described in DSM III, with a minimum score of 25 on the Montgomery Asberg Depressive Rating Scale (MADRS). The patient's ages ranged from 18 to 65. The only psychotropic medication allowed in association to the treatment was prazepam (up to 40 mg/day). Patients gave their written consent to the study. Assessment, using the Montgomery Asberg Depression Rating Scale (MADRS), the HARD diagram, the check list for somatic symptoms and side-effects was carried out before treatment and at the end of weeks 2, 4, 8. Assessment of anxiety using the Hamilton Anxiety Rating Scale (HARS) and of sleep disturbances using a sleep questionnaire was carried out before treatment and at week 4. The 8 items of the sleep questionnaire covers the complaints listed in criteria for insomnia disorders (307.42 DSM III-R). Clinical Global Impression (CGI), Therapeutic Index (TI), Tolerance Global Impression were assessed at end-point. The 2 groups were strictly comparable in respect to the clinical status at base line (diagnosis, history and duration of the depressive illness, MADRS and HARD diagram scores).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8275922

  14. Efficacy of sodium butyrate adjunct therapy in shigellosis: a randomized, double-blind, placebo-controlled clinical trial

    PubMed Central

    2012-01-01

    Background Treatment of shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of shigellosis in patients. Methods A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1β [IL-1β] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients. Results Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1β in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7. Conclusion Adjunct therapy with butyrate during shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool. Trial Registration Clinical

  15. A Subset of CD4/CD8 Double-Negative T Cells Expresses HIV Proteins in Patients on Antiretroviral Therapy

    PubMed Central

    DeMaster, Laura K.; Liu, Xiaohe; VanBelzen, D. Jake; Trinité, Benjamin; Zheng, Lingjie; Agosto, Luis M.; Migueles, Stephen A.; Connors, Mark; Sambucetti, Lidia; Levy, David N.; Pasternak, Alexander O.

    2015-01-01

    ABSTRACT A major goal in HIV eradication research is characterizing the reservoir cells that harbor HIV in the presence of antiretroviral therapy (ART), which reseed viremia after treatment is stopped. In general, it is assumed that the reservoir consists of CD4+ T cells that express no viral proteins. However, recent findings suggest that this may be an overly simplistic view and that the cells that contribute to the reservoir may be a diverse population that includes both CD4+ and CD4− cells. In this study, we directly infected resting CD4+ T cells and used fluorescence-activated cell sorting (FACS) and fiber-optic array scanning technology (FAST) to identify and image cells expressing HIV Gag. We found that Gag expression from integrated proviruses occurred in resting cells that lacked surface CD4, likely resulting from Nef- and Env-mediated receptor internalization. We also extended our approach to detect cells expressing HIV proteins in patients suppressed on ART. We found evidence that rare Gag+ cells persist during ART and that these cells are often negative for CD4. We propose that these double-negative α/β T cells that express HIV protein may be a component of the long-lived reservoir. IMPORTANCE A reservoir of infected cells persists in HIV-infected patients during antiretroviral therapy (ART) that leads to rebound of virus if treatment is stopped. In this study, we used flow cytometry and cell imaging to characterize protein expression in HIV-infected resting cells. HIV Gag protein can be directly detected in infected resting cells and occurs with simultaneous loss of CD4, consistent with the expression of additional viral proteins, such as Env and Nef. Gag+ CD4− cells can also be detected in suppressed patients, suggesting that a subset of infected cells express proteins during ART. Understanding the regulation of viral protein expression during ART will be key to designing effective strategies to eradicate HIV reservoirs. PMID:26537682

  16. A randomized, double-blind, placebo-controlled study of oral antioxidant supplement therapy in patients with dry eye syndrome

    PubMed Central

    Huang, Jehn-Yu; Yeh, Po-Ting; Hou, Yu-Chih

    2016-01-01

    Purpose To evaluate the efficacy of oral antioxidant supplementation in the treatment of patients with dry eye syndrome (DES). Methods A prospective, randomized, double-blinded study compared the effects of an antioxidant supplement (containing anthocyanosides, astaxanthin, vitamins A, C, and E, and several herbal extracts, including Cassiae semen and Ophiopogonis japonicus) with placebo on patients with DES. We assessed dry eye symptoms, visual acuity, Schirmer’s test, tear film breakup time, cornea and conjunctiva fluorescein staining, serum anti-SSA/anti-SSB antibodies, and the level of reactive oxygen species (ROS) in tears. The supplementation period was 8 weeks and patients were followed up every 4 weeks for 16 weeks. A linear mixed model was used to compare the groups, while within-group differences were tested by repeated-measures analysis of variance. Results Forty-three patients, 20 and 23 in treatment and placebo groups, respectively, completed the study. Liver and renal functions were normal. Diastolic blood pressure decreased in the treatment group. There were no significant differences in systolic blood pressure, dry eye symptoms, serum anti-SSA and anti-SSB, visual acuity, intraocular pressure, or fluorescein corneal staining between the groups. Tear film breakup time scores and Schirmer’s test without topical anesthesia significantly improved in the treatment group. Tear ROS level differed between the groups and decreased after treatment. Overall subjective impression revealed a significant improvement with treatment compared with placebo. Conclusion Oral antioxidant supplementations may increase tear production and improve tear film stability by reducing tear ROS. The vegetable-based antioxidant supplement used in this study is safe and can be utilized as an adjuvant therapy to conventional artificial tear therapy for patients with DES. PMID:27274185

  17. Influence of Double-Strand Break Repair on Radiation Therapy-Induced Acute Skin Reactions in Breast Cancer Patients

    SciTech Connect

    Mumbrekar, Kamalesh Dattaram; Fernandes, Donald Jerard; Goutham, Hassan Venkatesh; Sharan, Krishna; Vadhiraja, Bejadi Manjunath; Satyamoorthy, Kapaettu; Bola Sadashiva, Satish Rao

    2014-03-01

    Purpose: Curative radiation therapy (RT)-induced toxicity poses strong limitations for efficient RT and worsens the quality of life. The parameter that explains when and to what extent normal tissue toxicity in RT evolves would be of clinical relevance because of its predictive value and may provide an opportunity for personalized treatment approach. Methods and Materials: DNA double-strand breaks and repair were analyzed by microscopic γ-H2AX foci analysis in peripheral lymphocytes from 38 healthy donors and 80 breast cancer patients before RT, a 2 Gy challenge dose of x-ray exposed in vitro. Results: The actual damage (AD) at 0.25, 3, and 6 hours and percentage residual damage (PRD) at 3 and 6 hours were used as parameters to measure cellular radiosensitivity and correlated with RT-induced acute skin reactions in patients stratified as non-overresponders (NOR) (Radiation Therapy Oncology Group [RTOG] grade <2) and overresponders (OR) (RTOG grade ≥2). The results indicated that the basal and induced (at 0.25 and 3 hours) γ-H2AX foci numbers were nonsignificant (P>.05) between healthy control donors and the NOR and OR groups, whereas it was significant between ORs and healthy donors at 6 hours (P<.001). There was a significantly higher PRD in OR versus NOR (P<.05), OR versus healthy donors (P<.001) and NOR versus healthy donors (P<.01), supported further by the trend analysis (r=.2392; P=.0326 at 6 hours). Conclusions: Our findings strongly suggest that the measurement of PRD by performing γ-H2AX foci analysis has the potential to be developed into a clinically useful predictive assay.

  18. A double-blind comparative study of Chinese herbal medicine Jinlianqingre Effervescent Tablets in combination with conventional therapy for the treatment of uncomplicated hand, foot, and mouth disease.

    PubMed

    He, L-Y; Zhang, G-L; Yan, S-Y; Liu, Y; Zhao, C-S; Wang, X-L; Li, Y; Mi, Y-Q; Liu, Y-M; Li, C-P; Kou, Y-H; Li, Y; Chang, K; Meng, X-L; Sun, X-J; Zhao, T; Li, J; Wang, Y-Y; Liu, B-Y

    2014-08-01

    Chinese herbal medicine Jinlianqingre Effervescent Tablets (JET) are the recommended control measure for uncomplicated hand, foot, and mouth disease (HFMD) by the Ministry of Health of China. However, high-quality evidence to support this recommendation is limited. A total of 288 patients ranging in age from 1 to 13 years were randomly assigned to JET in combination with conventional therapy (mainly including the reduction of temperature by applying physical cooling paste or warm bathing), or conventional therapy with placebo group for 7 days. The objective was to test the hypothesis that JET combination therapy is more effective than conventional therapy for uncomplicated HFMD. A randomized, double-blind, placebo-controlled trial was designed. Our study showed that, compared with conventional therapy, the median time to fever resolution was significantly shorter in the JET combination therapy (8 vs. 80 h; p < 0.0001); the risk of fever resolution increased in the JET combination therapy [hazard ratio, 19.8; 95% confidence interval (CI), 12.8 to 30.7]; the median healing time of rash or oral ulcer was significantly shorter in the JET combination therapy (14 vs. 74 h; p < 0.0001); and the median symptom score for skin or oral mucosa lesions improved more rapidly in the JET combination therapy during the follow-up period. The median duration of hospital stay was 6 days in the JET combination therapy and 7 days in the conventional therapy (p < 0.0001). No significant adverse events and complications were found in both groups. The addition of JET to conventional therapy reduced fever clearance time, healing time of skin or oral mucosa lesions, and duration of hospital stay in children with uncomplicated HFMD. PMID:24643639

  19. Effect of pulsed electromagnetic field therapy on experimental pain: A double-blind, randomized study in healthy young adults.

    PubMed

    Beaulieu, Karen; Beland, Patricia; Pinard, Marilee; Handfield, Guilène; Handfield, Nicole; Goffaux, Philippe; Corriveau, Hélène; Léonard, Guillaume

    2016-01-01

    Previous studies suggested that pulsed electromagnetic field (PEMF) therapy can decrease pain. To date, however, it remains difficult to determine whether the analgesic effect observed in patients are attributable to a direct effect of PEMF on pain or to an indirect effect of PEMF on inflammation and healing. In the present study, we used an experimental pain paradigm to evaluate the direct effect of PEMF on pain intensity, pain unpleasantness, and temporal summation of pain. Twenty-four healthy subjects (mean age 22 ± 2 years; 9 males) participated in the experiment. Both real and sham PEMF were administered to every participant using a randomized, double-blind, cross-over design. For each visit, PEMF was applied for 10 minutes on the right forearm using a portable device. Experimental pain was evoked before (baseline) and after PEMF with a 9 cm(2) Pelletier-type thermode, applied on the right forearm (120 s stimulation; temperature individually adjusted to produce moderate baseline pain). Pain intensity and unpleasantness were evaluated using a 0-100 numerical pain rating scale. Temporal summation was evaluated by comparing pain intensity ratings obtained at the end of tonic nociceptive stimulation (120 s) with pain intensity ratings obtained after 60 s of stimulation. When compared to baseline, there was no change in pain intensity and unpleasantness following the application of real or sham PEMF. PEMF did not affect temporal summation. The present observations suggest that PEMF does not directly influence heat pain perception in healthy individuals. PMID:27014804

  20. Effect of radial shock wave therapy for carpal tunnel syndrome: A prospective randomized, double-blind, placebo-controlled trial.

    PubMed

    Wu, Yung-Tsan; Ke, Ming-Jen; Chou, Yu-Ching; Chang, Chih-Ya; Lin, Ching-Yueh; Li, Tsung-Ying; Shih, Feng-Mei; Chen, Liang-Cheng

    2016-06-01

    Three recent studies demonstrated the positive effect of extracorporeal shock wave therapy (ESWT) for treating carpal tunnel syndrome (CTS). However, none have entirely proved the effects of ESWT on CTS because all studies had a small sample size and lacked a placebo-controlled design. Moreover, radial ESWT (rESWT) has not been used to treat CTS. We conducted a prospective randomized, controlled, double-blinded study to assess the effect of rESWT for treating CTS. Thirty-four enrolled patients (40 wrists) were randomized into intervention and control groups (20 wrists in each). Participants in the intervention group underwent three sessions of rESWT with nightly splinting, whereas those in the control group underwent sham rESWT with nightly splinting. The primary outcome was visual analog scale (VAS), whereas the secondary outcomes included the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ), cross-sectional area (CSA) of the median nerve, sensory nerve conduction velocity of the median nerve, and finger pinch strength. Evaluations were performed before treatment and at 1, 4, 8, and 12 weeks after the third rESWT session. A significantly greater improvement in the VAS, BCTQ scores, and CSA of the median nerve was noted in the intervention group throughout the study as compared to the control group (except for BCTQ severity at week 12 and CSA at weeks 1 and 4) (p < 0.05). This is the first study to assess rESWT in a randomized placebo-controlled trial and demonstrate that rESWT is a safe and effective method for relieving pain and disability in patients with CTS. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:977-984, 2016. PMID:26610183

  1. L-arginine and Vitamin D Adjunctive Therapies in Pulmonary Tuberculosis: A Randomised, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Ralph, Anna P.; Waramori, Govert; Pontororing, Gysje J.; Kenangalem, Enny; Wiguna, Andri; Tjitra, Emiliana; Sandjaja; Lolong, Dina B.; Yeo, Tsin W.; Chatfield, Mark D.; Soemanto, Retno K.; Bastian, Ivan; Lumb, Richard; Maguire, Graeme P.; Eisman, John; Price, Ric N.; Morris, Peter S.; Kelly, Paul M.; Anstey, Nicholas M.

    2013-01-01

    Background Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB). Methods In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339. Results 200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference −3%, 95% CI −19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI −9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes. Conclusion Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained

  2. Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection

    PubMed Central

    Waldenström, Jesper; Westin, Johan; Nyström, Kristina; Christensen, Peer; Dalgard, Olav; Färkkilä, Martti; Lindahl, Karin; Nilsson, Staffan; Norkrans, Gunnar; Krarup, Henrik; Norrgren, Hans; Rauning Buhl, Mads; Stenmark, Stephan; Lagging, Martin

    2016-01-01

    In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard-of-care (SOC) ribavirin dosing concurrent with pegIFN-α. Four weeks of ribavirin mono-therapy resulted in a mean 0.46 log10 IU/mL HCV RNA reduction differentially regulated across IL28B genotypes (0.89 vs. 0.21 log10 IU/mL for CC and CT/TT respectively; P = 0.006), increased likelihood of undetectable HCV RNA week 4 after initiating pegIFN-α and thus shortened treatment duration (P<0.05), and decreased median IP-10 concentration from 550 to 345 pg/mL (P<0.001). Both experimental strategies impacted on ribavirin concentrations, and high levels were achieved after one week of double dosing. However, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an anti-viral effect differently regulated across IL28B genotypes. Trial Registration ClinicalTrials.gov NCT01226771 PMID:27167219

  3. Synthesis and Characterization of Chitosan-Coated Near-Infrared (NIR) Layered Double Hydroxide-Indocyanine Green Nanocomposites for Potential Applications in Photodynamic Therapy

    PubMed Central

    Wei, Pei-Ru; Kuthati, Yaswanth; Kankala, Ranjith Kumar; Lee, Chia-Hung

    2015-01-01

    We designed a study for photodynamic therapy (PDT) using chitosan coated Mg–Al layered double hydroxide (LDH) nanoparticles as the delivery system. A Food and Drug Administration (FDA) approved near-infrared (NIR) fluorescent dye, indocyanine green (ICG) with photoactive properties was intercalated into amine modified LDH interlayers by ion-exchange. The efficient positively charged polymer (chitosan (CS)) coating was achieved by the cross linkage using surface amine groups modified on the LDH nanoparticle surface with glutaraldehyde as a spacer. The unique hybridization of organic-inorganic nanocomposites rendered more effective and successful photodynamic therapy due to the photosensitizer stabilization in the interlayer of LDH, which prevents the leaching and metabolization of the photosensitizer in the physiological conditions. The results indicated that the polymer coating and the number of polymer coats have a significant impact on the photo-toxicity of the nano-composites. The double layer chitosan coated LDH–NH2–ICG nanoparticles exhibited enhanced photo therapeutic effect compared with uncoated LDH–NH2–ICG and single layer chitosan-coated LDH–NH2–ICG due to the enhanced protection to photosensitizers against photo and thermal degradations. This new class of organic-inorganic hybrid nanocomposites can potentially serve as a platform for future non-invasive cancer diagnosis and therapy. PMID:26340627

  4. Synthesis and Characterization of Chitosan-Coated Near-Infrared (NIR) Layered Double Hydroxide-Indocyanine Green Nanocomposites for Potential Applications in Photodynamic Therapy.

    PubMed

    Wei, Pei-Ru; Kuthati, Yaswanth; Kankala, Ranjith Kumar; Lee, Chia-Hung

    2015-01-01

    We designed a study for photodynamic therapy (PDT) using chitosan coated Mg-Al layered double hydroxide (LDH) nanoparticles as the delivery system. A Food and Drug Administration (FDA) approved near-infrared (NIR) fluorescent dye, indocyanine green (ICG) with photoactive properties was intercalated into amine modified LDH interlayers by ion-exchange. The efficient positively charged polymer (chitosan (CS)) coating was achieved by the cross linkage using surface amine groups modified on the LDH nanoparticle surface with glutaraldehyde as a spacer. The unique hybridization of organic-inorganic nanocomposites rendered more effective and successful photodynamic therapy due to the photosensitizer stabilization in the interlayer of LDH, which prevents the leaching and metabolization of the photosensitizer in the physiological conditions. The results indicated that the polymer coating and the number of polymer coats have a significant impact on the photo-toxicity of the nano-composites. The double layer chitosan coated LDH-NH₂-ICG nanoparticles exhibited enhanced photo therapeutic effect compared with uncoated LDH-NH₂-ICG and single layer chitosan-coated LDH-NH₂-ICG due to the enhanced protection to photosensitizers against photo and thermal degradations. This new class of organic-inorganic hybrid nanocomposites can potentially serve as a platform for future non-invasive cancer diagnosis and therapy. PMID:26340627

  5. Efficacy of low-level laser therapy in the management of tinnitus due to noise-induced hearing loss: a double-blind randomized clinical trial.

    PubMed

    Mollasadeghi, Abolfazl; Mirmohammadi, Seyyed Jalil; Mehrparvar, Amir Houshang; Davari, Mohammad Hossein; Shokouh, Pedram; Mostaghaci, Mehrdad; Baradaranfar, Mohammad Hossein; Bahaloo, Maryam

    2013-01-01

    Background. Several remedial modalities for the treatment of tinnitus have been proposed, but an effective standard treatment is still to be confirmed. In the present study, we aimed to evaluate the effect of low-level laser therapy on tinnitus accompanied by noise-induced hearing loss. Methods. This was a double-blind randomized clinical trial on subjects suffering from tinnitus accompanied by noise-induced hearing loss. The study intervention was 20 sessions of low-level laser therapy every other day, 20 minutes each session. Tinnitus was assessed by three methods (visual analog scale, tinnitus handicap inventory, and tinnitus loudness) at baseline, immediately and 3 months after the intervention. Results. All subjects were male workers with age range of 30-51 years. The mean tinnitus duration was 1.85 ± 0.78 years. All three measurement methods have shown improved values after laser therapy compared with the placebo both immediately and 3 months after treatment. Laser therapy revealed a U-shaped efficacy throughout the course of follow-up. Nonresponse rate of the intervention was 57% and 70% in the two assessment time points, respectively. Conclusion. This study found low-level laser therapy to be effective in alleviating tinnitus in patients with noise-induced hearing loss, although this effect has faded after 3 months of follow-up. This trial is registered with the Australian New Zealand clinical trials registry with identifier ACTRN12612000455864). PMID:24288494

  6. Efficacy of Low-Level Laser Therapy in the Management of Tinnitus due to Noise-Induced Hearing Loss: A Double-Blind Randomized Clinical Trial

    PubMed Central

    Mollasadeghi, Abolfazl; Mirmohammadi, Seyyed Jalil; Mehrparvar, Amir Houshang; Baradaranfar, Mohammad Hossein

    2013-01-01

    Background. Several remedial modalities for the treatment of tinnitus have been proposed, but an effective standard treatment is still to be confirmed. In the present study, we aimed to evaluate the effect of low-level laser therapy on tinnitus accompanied by noise-induced hearing loss. Methods. This was a double-blind randomized clinical trial on subjects suffering from tinnitus accompanied by noise-induced hearing loss. The study intervention was 20 sessions of low-level laser therapy every other day, 20 minutes each session. Tinnitus was assessed by three methods (visual analog scale, tinnitus handicap inventory, and tinnitus loudness) at baseline, immediately and 3 months after the intervention. Results. All subjects were male workers with age range of 30–51 years. The mean tinnitus duration was 1.85 ± 0.78 years. All three measurement methods have shown improved values after laser therapy compared with the placebo both immediately and 3 months after treatment. Laser therapy revealed a U-shaped efficacy throughout the course of follow-up. Nonresponse rate of the intervention was 57% and 70% in the two assessment time points, respectively. Conclusion. This study found low-level laser therapy to be effective in alleviating tinnitus in patients with noise-induced hearing loss, although this effect has faded after 3 months of follow-up. This trial is registered with the Australian New Zealand clinical trials registry with identifier ACTRN12612000455864). PMID:24288494

  7. SU-E-J-53: Dosimetric Evaluation at Volumetric Modulated Arc Therapy for Treatment of Prostate Cancer Using Single Or Double Arcs

    SciTech Connect

    Silva, D; Salmon, H; Pavan, G; Nardi, S; Anderson, E; Fairbanks, L; Junior, J; Cursino, F; Colodette, K

    2014-06-01

    Purpose: Evaluate and compare retrospective prostate treatment plan using Volumetric Modulated Arc Therapy (RapidArc™ - Varian) technique with single or double arcs at COI Group. Methods: Ten patients with present prostate and seminal vesicle neoplasia were replanned as a target treatment volume and a prescribed dose of 78 Gy. A baseline planning, using single arc, was developed for each case reaching for the best result on PTV, in order to minimize the dose on organs at risk (OAR). Maintaining the same optimization objectives used on baseline plan, two copies for optimizing single and double arcs, have been developed. The plans were performed with 10 MV photon beam energy on Eclipse software, version 11.0, making use of Trilogy linear accelerator with Millenium HD120 multileaf collimator. Comparisons on PTV have been performed, such as: maximum, minimum and mean dose, gradient dose, as well as the quantity of monitor units, treatment time and homogeneity and conformity index. OARs constrains dose have been evaluated, comparing both optimizations. Results: Regarding PTV coverage, the difference of the minimum, maximum and mean dose were 1.28%, 0.7% and 0.2% respectively higher for single arc. When analyzed the index of homogeneity found a difference of 0.99% higher when compared with double arcs. However homogeneity index was 0.97% lower on average by using single arc. The doses on the OARs, in both cases, were in compliance to the recommended limits RTOG 0415. With the use of single arc, the quantity of monitor units was 10,1% lower, as well as the Beam-On time, 41,78%, when comparing double arcs, respectively. Conclusion: Concerning the optimization of patients with present prostate and seminal vesicle neoplasia, the use of single arc reaches similar objectives, when compared to double arcs, in order to decrease the treatment time and the quantity of monitor units.

  8. The Effectiveness of Group Cognitive Behavioral Therapy in Treating Obsessive-Compulsive Disorder in Women with Multiple Sclerosis (MS): A randomized double-blind controlled trial

    PubMed Central

    Sayyah, Mehdi; Bagheri, Parisa; Karimi, Negar; Ghasemzadeh, Azizreza

    2016-01-01

    Background Obsessive-compulsive disorder (OCD) is one of the most prevalent psychiatric disorders and can cause problems for individuals in all aspects of life, including social and personal dimensions. Objective To study the effect of group cognitive-behavioral therapy on the reduction of OCD symptoms in female participants with multiple sclerosis (MS). Methods This double-blind randomized control trial was conducted from May 2012 to December 2014. The participants included 75 patients with MS who suffered from OCD and were referred to the Loghman Hakim and Imam Khomeini hospitals in Tehran, Iran. Thirty participants had been diagnosed through Yale-Brown Obsessive-Compulsive Symptoms (Y-BOCS). The participants were randomly divided into an experimental group (n=15) and a control group (n=15). Eleven sessions of cognitive-behavioral therapy were provided for the experimental group. Patients in the control group continued with their normal living. Hypotheses were tested using an analysis of covariance (ANCOVA). Results A significant reduction was found in the experimental group’s obsessive-compulsive symptoms after cognitive-behavioral therapy (p<0.001). In addition, mean scores for participants in the experimental group were significantly lower than for those in the control group (p=0.000). Conclusion It can be inferred that cognitive-behavioral therapy could considerably reduce OCD symptoms in women with MS. The application of this method by therapists, especially Iranian clinicians, is recommended. PMID:27279999

  9. A randomized, double-blind, sham-controlled study of static electric field therapy by high voltage alternating current for active rheumatoid arthritis.

    PubMed

    Naito, Yuji; Yamaguchi, Shinnichi; Mori, Yasuhiro; Nakajima, Kouji; Hashimoto, Sanshiro; Tomaru, Masakazu; Satoh, Yoshihiko; Hitomi, Yuji; Karita, Masakazu; Hiwatashi, Tomoaki; Kawahito, Yutaka; Yoshikawa, Toshikazu

    2013-07-01

    Static electric field therapy by high voltage alternating current (EF-HVAC) is a traditional complementary Japanese medicine used for headache, shoulder stiffness, chronic constipation and insomnia. Open-label studies and clinical experience in Japan have suggested that this electric field therapy is safe and effective in treating chronic arthritis. We evaluated the efficacy of EF-HVAC therapy in a randomized, double-blinded, sham-controlled trial in patients with active rheumatoid arthritis (RA) in community-based general physician centers. Thirty patients fulfilling American College of Rheumatology (ACR) criteria for RA were treated with EF-HVAC therapy with the LEGACIS PLUS System (COCOROCA Corp., Tokyo, Japan) or sham therapy for 12 weeks and followed for 4 weeks without treatment. The disease activity score 28 (DAS28-CRP), visual analogue scale for pain (VAS), modified health assessment questionnaire (MHAQ), and inflammatory parameters were used as the outcome variable. Twenty four patients (n = 12 in each group) were analyzed by a per protocol analysis. Although a significant reduction in DAS28-CRP was observed in EF-HVAC group at 8 and 12 weeks compared to before treatment, there were no significant differences in DAS28-CRP scores during treatment between two groups. The scale of VAS was also significantly decreased by the treatment with EF-HVAC compared to before treatment, in addition, the scale of VAS in EF-HVAC group was significantly lower than sham group at 8 and 12 weeks. Changes in another parameters including MHAQ were not significant between before and after treatment, or by all comparative study between two groups. There were no adverse events related the treatment. In conclusion, the EF-HVAC therapy has a beneficial effect on the improvement to subjective pain of RA. PMID:23874073

  10. Dual Antiplatelet Therapy after Coronary Artery Bypass Graft Surgery: A Review.

    PubMed

    Soomro, Hala; Aleem, Salik; Alam, Ali; Qadeer, Mohammad Ali; Essam, Nabeeha; Siddiqui, Anas Ahmed; Mansuri, Muhammad Fasih; Fatima, Huda; Raza, Ali; Sultan, Ayyaz Alam; Jameel, Rohail; Begg, Maha; Khan, Maaz Hasan; Musharraf, Muhammad Bazil; Burhan, Arbab; Lashari, Muhammad Nawaz

    2016-01-01

    Coronary artery bypass graft surgery (CABG) is the gold standard treatment for relieving angina symptoms and reducing mortality among ischemic heart disease patients. As post-operative thrombosis of the grafts has been a frequent complication of CABG, antiplatelet therapy remains essential to maintain graft patency. Since a long time, aspirin has been used as a single anti-platelet agent post CABG. However, in some high risk patients aspirin alone is insufficient in preventing graft occlusion. Therefore, dual antiplatelet therapy involving aspirin plus clopidogrel is becoming increasingly popular. Aspirin plus clopidogrel therapy has proved to be highly efficacious in patients with acute coronary syndrome; however, its role in patients after CABG has remained unclear. In this review, we outline the effects of dual antiplatelet therapy involving aspirin plus clopidogrel with respect to graft patency, post-operative angina/myocardial infarction, major bleeding event and mortality. PMID:27530557

  11. Combined modality doxorubicin-based chemotherapy and chitosan-mediated p53 gene therapy using double-walled microspheres for treatment of human hepatocellular carcinoma

    PubMed Central

    Xu, Qingxing; Leong, Jiayu; Chua, Qi Yi; Chi, Yu Tse; Chow, Pierce Kah-Hoe; Pack, Daniel W.; Wang, Chi-Hwa

    2013-01-01

    The therapeutic efficiency of combined chemotherapy and gene therapy on human hepatocellular carcinoma HepG2 cells was investigated using double-walled microspheres that consisted of a poly(D,L-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(L-lactic acid) (PLLA) shell layer and fabricated via the precision particle fabrication (PPF) technique. Here, double-walled microspheres were used to deliver doxorubicin (Dox) and/or chitosan-DNA nanoparticles containing the gene encoding the p53 tumor suppressor protein (chi-p53), loaded in the core and shell phases, respectively. Preliminary studies on chi-DNA nanoparticles were performed to optimize gene transfer to HepG2 cells. The transfection efficiency of chi-DNA nanoparticles was optimal at an N/P ratio of 7. In comparison to the 25-kDa branched polyethylenimine (PEI), chitosan showed no inherent toxicity towards the cells. Next, the therapeutic efficiencies of Dox and/or chi-p53 in microsphere formulations were compared to free drug(s) and evaluated in terms of growth inhibition, and cellular expression of tumor suppressor p53 and apoptotic caspase 3 proteins. Overall, the combined Dox and chi-p53 treatment exhibited enhanced cytotoxicity as compared to either Dox or chi-p53 treatments alone. Moreover, the antiproliferative effect was more substantial when cells were treated with microspheres than those treated with free drugs. High p53 expression was maintained during a five-day period, and was largely due to the controlled and sustained release of the microspheres. Moreover, increased activation of caspase 3 was observed, and was likely to have been facilitated by high levels of p53 expression. Overall, double-walled microspheres present a promising dual anticancer delivery system for combined chemotherapy and gene therapy. PMID:23578555

  12. Combined modality doxorubicin-based chemotherapy and chitosan-mediated p53 gene therapy using double-walled microspheres for treatment of human hepatocellular carcinoma.

    PubMed

    Xu, Qingxing; Leong, Jiayu; Chua, Qi Yi; Chi, Yu Tse; Chow, Pierce Kah-Hoe; Pack, Daniel W; Wang, Chi-Hwa

    2013-07-01

    The therapeutic efficiency of combined chemotherapy and gene therapy on human hepatocellular carcinoma HepG2 cells was investigated using double-walled microspheres that consisted of a poly(D,L-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(L-lactic acid) (PLLA) shell layer and fabricated via the precision particle fabrication (PPF) technique. Here, double-walled microspheres were used to deliver doxorubicin (Dox) and/or chitosan-DNA nanoparticles containing the gene encoding the p53 tumor suppressor protein (chi-p53), loaded in the core and shell phases, respectively. Preliminary studies on chi-DNA nanoparticles were performed to optimize gene transfer to HepG2 cells. The transfection efficiency of chi-DNA nanoparticles was optimal at an N/P ratio of 7. In comparison to the 25-kDa branched polyethylenimine (PEI), chitosan showed no inherent toxicity towards the cells. Next, the therapeutic efficiencies of Dox and/or chi-p53 in microsphere formulations were compared to free drug(s) and evaluated in terms of growth inhibition, and cellular expression of tumor suppressor p53 and apoptotic caspase 3 proteins. Overall, the combined Dox and chi-p53 treatment exhibited enhanced cytotoxicity as compared to either Dox or chi-p53 treatments alone. Moreover, the antiproliferative effect was more substantial when cells were treated with microspheres than those treated with free drugs. High p53 expression was maintained during a five-day period, and was largely due to the controlled and sustained release of the microspheres. Moreover, increased activation of caspase 3 was observed, and was likely to have been facilitated by high levels of p53 expression. Overall, double-walled microspheres present a promising dual anticancer delivery system for combined chemotherapy and gene therapy. PMID:23578555

  13. Successful Prasugrel Rescue Therapy in Clopidogrel Resistant Patients Who Had Recurrent Stent Thrombosis of Drug-Eluting-Stent: The Role of Prasugrel in Clopidogrel Nonresponders

    PubMed Central

    Lee, Seung-Hyun; Kim, Byeong-Keuk; Oh, Jaewon; Park, Jin Su; Lee, Dong-Jun; Lee, Han-Cheol; Kim, Jin Ho

    2013-01-01

    Stent thrombosis is a very serious problem after drug-eluting stent (DES) implantation even though its incidence is about or less than 1%. As the clopidogrel resistance is expected to play an important role in the occurrence of stent thrombosis, new anti-platelet agents overcoming this issue can give us another choice. We experienced a case of a 58-year-old male with successful prasugrel rescue therapy in a patient with clopidogrel resistance who had recurrent stent thrombosis following DES implantation. PMID:23755082

  14. A double blind, randomised controlled trial of glycerol adjuvant therapy in adult bacterial meningitis in a high HIV seroprevalence setting in Malawi

    PubMed Central

    Ajdukiewicz, Katherine M.B.; Cartwright, Katharine E.; Scarborough, Matthew; Mwambene, James B.; Goodson, Patrick; Molyneux, Malcolm E.; Zijlstra, Eduard E.; French, Neil; Whitty, Christopher J.M.; Lalloo, David G.

    2014-01-01

    Summary Background Southern Africa has a high incidence of bacterial meningitis in adults, often associated with HIV co-infection. Even with appropriate antibiotic therapy, mortality exceeds 50% and is not improved with corticosteroids. Glycerol adjuvant therapy reduced mortality and long-term morbidity (deafness) in bacterial meningitis in children and is being promoted. If similarly effective in adults, glycerol would provide a cheap, available adjuvant therapy in Africa. Methods Following a dose-finding study, we conducted a randomised double-blind placebo-controlled trial of oral glycerol in adults with bacterial meningitis. Patients with clinical and CSF findings suggestive of bacterial meningitis were randomised either to glycerol or an equivalent volume of sugar solution. The primary outcome was mortality at 40 days with secondary outcomes including disability and mortality restricted to pneumococcal disease. Findings 75ml glycerol QDS was best tolerated and was used for the main study. 265 patients were randomised to receive glycerol or placebo. The trial was stopped early on the advice of the Data and Safety Monitoring Board (DSMB) following a planned interim analysis. Mortality by day 40 was 61/125 (49%) in the placebo and 86/136 (69%) in the glycerol arms, Adjusted Odds Ratio 2·4 (95% CI 1·3-4·2 p0·003). There was no benefit from glycerol for death and disability by day 40 by intention to treat or in predefined subgroups. Two serious adverse events occurred possibly due to study drug. Interpretation Oral glycerol therapy did not improve mortality in adults with bacterial meningitis and cannot be recommended as a suitable adjuvant therapy in resource-poor settings with a high HIV prevalence. PMID:21334262

  15. Low-level laser therapy for treatment of chemotherapy-induced oral mucositis in childhood: a randomized double-blind controlled study.

    PubMed

    Amadori, Francesca; Bardellini, Elena; Conti, Giulio; Pedrini, Nicola; Schumacher, Richard Fabian; Majorana, Alessandra

    2016-08-01

    The aim of this study was to verify if low-level laser therapy could be useful to reduce chemotherapy-related oral mucositis grading and pain in childhood undergoing chemotherapy. A randomized double-blind clinical trial was carried out. Patients from 3 to 18 years of age undergoing cancer therapy and presenting OM grade 2 or more were eligible for this study. Patients were randomly divided in two groups: group A received laser therapy from the day of OM diagnosis and other 3 consecutive days (830 nm wavelength, power 150 mW, spot size 1 cm(2), 30 s per cm(2), energy density 4.5 J/cm(2)); group B received sham therapy (placebo) with the same timing. Two blind clinicians performed OM scoring and pain evaluation at day 1 (immediately before the beginning of laser treatment-T0), day 4 (after finishing laser therapy cycle-T1) and at day 7 (T2) as follow-up. A total of 123 patients were included in the study. Group A was composed of 62 children while group B is 61; in both groups, there was a progressive reduction in grade of OM, and at day 7, not every mucosal lesion disappeared. The difference in the decline of OM grading between the two groups resulted not statistically significant (p = 0.07). A statistically significant difference in pain reduction between two groups both at T1 and at T2 (p < 0.005) was observed. This study demonstrated the efficacy of LLLT in reducing pain due to chemotherapy-induced oral mucositis in children, while no significant benefit was noted in reducing OM grade. PMID:27272517

  16. Sono-Electro-Magnetic Therapy for Treating Chronic Pelvic Pain Syndrome in Men: A Randomized, Placebo-Controlled, Double-Blind Trial

    PubMed Central

    Kessler, Thomas M.; Mordasini, Livio; Weisstanner, Christian; Jüni, Peter; da Costa, Bruno R.; Wiest, Roland; Thalmann, George N.

    2014-01-01

    Objective To assess the efficacy and safety of sono-electro-magnetic therapy compared to placebo in men with refractory CPPS. Patients and Methods In a randomized, placebo-controlled, double-blind single center trial, we assessed the effect of sono-electro-magnetic therapy in men with treatment refractory CPPS. Sixty male patients were randomly assigned to treatment with either sono-electro-magnetic (n = 30) or placebo therapy (n = 30) for 12 weeks. The primary outcome was a change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) from baseline to 12 weeks. Results The 12-week difference between sono-electro-magnetic and placebo therapy in changes of the NIH-CPSI total score was −3.1 points (95% CI −6.8 to 0.6, p = 0.11). In secondary comparisons of NIH-CPSI sub-scores, we found differences between groups most pronounced for the quality-of-life sub-score (difference at 12 weeks −1.6, 95% CI −2.8 to −0.4, p = 0.015). In stratified analyses, the benefit of sono-electro-magnetic therapy appeared more pronounced among patients who had a symptom duration of 12 months or less (difference in NIH-CPSI total score −8.3, 95% CI −14.5 to 2.6) than in patients with a longer symptom duration (−0.8, 95% CI −4.6 to 3.1; p for interaction = 0.023). Conclusions Sono-electro-magnetic therapy did not result in a significant improvement of symptoms in the overall cohort of treatment refractory CPPS patients compared to placebo treatment. Subgroup analysis indicates, however, that patients with a symptom-duration of 12 months or less may benefit from sono-electro-magnetic therapy, warranting larger randomized controlled trials in this subpopulation. Trial Registration ClinicalTrials.gov NCT00688506 PMID:25546177

  17. Comparison of integrated traditional Chinese and western medicine therapy on vascular cognitive impairment with no dementia.

    PubMed

    Wang, L P; Zhang, X Y; Liu, N; Ma, Z Z; Fang, D S

    2015-01-01

    The aim of this study was to investigate the clinical effect of western medicine therapy assisted by Ginkgo biloba tablets (GBT) in patients with vascular cognitive impairment with no dementia (VCIND). Eighty patients with VCIND were randomly divided into two groups: the conventional treatment group (control group) and the combined treatment group. The conventional treatment group was provided with anti-platelet aggregation conventional treatment. In this group, 75 mg aspirin was given three times a day for 3 months, whereas the combined treatment group was given 19.2 mg GBT three times a day for 3 months along with conventional anti-platelet aggregation treatment. Montreal cognitive assessment (MoCA) and transcranial Doppler ultrasonography were used to observe changes in cognitive ability and cerebral blood flow in patients with VCIND before and after treatment in the two groups. After 3 months of treatment, the MoCA scores of execution, attention, abstraction, delayed memory, and orientation were significantly increased in the combined treatment group compared with those before treatment and those in the control group after treatment. In addition, the blood flow velocity of the anterior cerebral artery was significantly increased in the combined treatment group. GBT can improve the therapeutic efficacy, cognitive ability, and cerebral blood flow supply of patients with VCIND. PMID:25966264

  18. Posttreatment prostatic-specific antigen doubling time as a surrogate endpoint for prostate cancer-specific survival: An analysis of Radiation Therapy Oncology Group Protocol 92-02

    SciTech Connect

    Valicenti, Richard K. . E-mail: Richard.Valicenti@mail.tju.edu; DeSilvio, Michelle; Hanks, Gerald E.; Porter, Arthur; Brereton, Harmar; Rosenthal, Seth A.; Shipley, William U.; Sandler, Howard M.

    2006-11-15

    Purpose: We evaluated whether posttreatment prostatic-specific antigen doubling time (PSADT) was predictive of prostate cancer mortality by testing the Prentice requirements for a surrogate endpoint. Methods and Materials: We analyzed posttreatment PSA measurements in a cohort of 1,514 men with localized prostate cancer (T2c-4 and PSA level <150 ng/mL), treated and monitored prospectively on Radiation Therapy Oncology Group Protocol 92-02. From June 1992 to April 1995, men were randomized to neoadjuvant androgen deprivation and 65-70 Gy of radiation therapy (n = 761), or in combination with 24 months of adjuvant androgen deprivation (n = 753). Using an adjusted Cox proportional hazards model, we tested if PSADT was prognostic and independent of randomized treatment in this cohort. The endpoints were time to PSADT (assuming first-order kinetics for a minimum of 3 rising PSA measurements) and cancer-specific survival (CSS). Results: After a median follow-up time of 5.9 years, randomized treatment was a significant predictor for CSS (p{sub Cox} = 0.002), PSADT <6 months (p{sub Cox} < 0.001), PSADT <9 months (p{sub Cox} < 0.001), and PSADT <12 months (p{sub Cox} < 0.001) but not for PSADT <3 (p{sub Cox} = 0.4). The significant posttreatment PSADTs were also significant predictors of CSS (p{sub Cox}< 0.001). After adjusting for T stage, Gleason score and PSA, all of Prentice's requirements were not met, indicating that the effect of PSADT on CSS was not independent of the randomized treatment. Conclusions: Prostatic specific antigen doubling time is significantly associated with CSS, but did not meet all of Prentice's requirements for a surrogate endpoint of CSS. Thus, the risk of dying of prostate cancer is not fully explained by PSADT.

  19. Cellular Therapy With Ixmyelocel-T to Treat Critical Limb Ischemia: The Randomized, Double-blind, Placebo-controlled RESTORE-CLI Trial

    PubMed Central

    Powell, Richard J; Marston, William A; Berceli, Scott A; Guzman, Raul; Henry, Timothy D; Longcore, Amy T; Stern, Theresa P; Watling, Sharon; Bartel, Ronnda L

    2012-01-01

    Ixmyelocel-T is a patient-specific, expanded, multicellular therapy evaluated in patients with lower extremity critical limb ischemia (CLI) with no options for revascularization. This randomized, double-blind, placebo-controlled, phase 2 trial (RESTORE-CLI) compared the efficacy and safety of intramuscular injections of ixmyelocel-T with placebo. Patients received one-time injections over 20 locations in a single leg and were followed for 12 months. Safety assessments included occurrence of adverse events. Efficacy assessments included time to first occurrence of treatment failure (TTF; major amputation of injected leg; all-cause mortality; doubling of total wound surface area from baseline; de novo gangrene) and amputation-free survival (AFS; major amputation of injected leg; all-cause mortality). A total of 77 patients underwent bone marrow or sham aspiration; 72 patients received ixmyelocel-T (48 patients) or placebo (24 patients). Adverse event rates were similar. Ixmyelocel-T treatment led to a significantly prolonged TTF (P = 0.0032, logrank test). AFS had a clinically meaningful 32% reduction in event rate that was not statistically significant (P = 0.3880, logrank test). Treatment effect in post hoc analyses of patients with baseline wounds was more pronounced (TTF: P < 0.0001, AFS: P = 0.0802, logrank test). Ixmyelocel-T treatment was well tolerated and may offer a potential new treatment option. PMID:22453769

  20. Efficacy of Levofloxacin and Rifaximin based Quadruple Therapy in Helicobacter pylori Associated Gastroduodenal Disease: A Double-Blind, Randomized Controlled Trial

    PubMed Central

    Choi, Kang Hyun; Lee, Kang-Moon; Paik, Chang Nyol; Kim, Eun Jung; Kang, Bong Koo; Oak, Ju Hyun; Jung, Sung Hoon

    2011-01-01

    The aim of this study was to evaluate the efficacy of levofloxacin and rifaximin based quadruple regimen as first-line treatment for Helicobacter pylori infection. A prospectively randomized, double-blinded, parallel group, comparative study was performed. Three hundred consecutive H. pylori positive patients were randomized to receive: omeprazole, amoxicillin, clarithromycin (OAC); omeprazole, amoxicillin, levofloxacin (OAL); and omeprazole, amoxicillin, levofloxacin, rifaximin (OAL-R). The eradication rates in the intention to treat (ITT) and per protocol (PP) analyses were: OAC, 77.8% and 85.6%; OAL, 65.3% and 73.6%; and OAL-R, 74.5% and 80.2%. The eradication rate achieved with OAC was higher than with OAL on the ITT (P = 0.05) and PP analysis (P = 0.04). OAL-R regimen was not inferior to OAC. The frequency of moderate to severe adverse effects was significantly higher in OAC treatment group. Especially, diarrhea was most common complaint, and there was a significantly low rate of moderate to severe diarrhea with the rifaximin containing regimen. In conclusion, the levofloxacin and rifaximin based regimen comes up to the standard triple therapy, but has a limited efficacy in a Korean cohort. The rifaximin containing regimen has a very high safety profile for H. pylori eradication therapy. PMID:21655065

  1. Efficacy of levofloxacin and rifaximin based quadruple therapy in Helicobacter pylori associated gastroduodenal disease: a double-blind, randomized controlled trial.

    PubMed

    Choi, Kang Hyun; Chung, Woo Chul; Lee, Kang-Moon; Paik, Chang Nyol; Kim, Eun Jung; Kang, Bong Koo; Oak, Ju Hyun; Jung, Sung Hoon

    2011-06-01

    The aim of this study was to evaluate the efficacy of levofloxacin and rifaximin based quadruple regimen as first-line treatment for Helicobacter pylori infection. A prospectively randomized, double-blinded, parallel group, comparative study was performed. Three hundred consecutive H. pylori positive patients were randomized to receive: omeprazole, amoxicillin, clarithromycin (OAC); omeprazole, amoxicillin, levofloxacin (OAL); and omeprazole, amoxicillin, levofloxacin, rifaximin (OAL-R). The eradication rates in the intention to treat (ITT) and per protocol (PP) analyses were: OAC, 77.8% and 85.6%; OAL, 65.3% and 73.6%; and OAL-R, 74.5% and 80.2%. The eradication rate achieved with OAC was higher than with OAL on the ITT (P = 0.05) and PP analysis (P = 0.04). OAL-R regimen was not inferior to OAC. The frequency of moderate to severe adverse effects was significantly higher in OAC treatment group. Especially, diarrhea was most common complaint, and there was a significantly low rate of moderate to severe diarrhea with the rifaximin containing regimen. In conclusion, the levofloxacin and rifaximin based regimen comes up to the standard triple therapy, but has a limited efficacy in a Korean cohort. The rifaximin containing regimen has a very high safety profile for H. pylori eradication therapy. PMID:21655065

  2. A fine-scale dissection of the DNA double-strand break repair machinery and its implications for breast cancer therapy

    PubMed Central

    Liu, Chao; Srihari, Sriganesh; Cao, Kim-Anh Lê; Chenevix-Trench, Georgia; Simpson, Peter T.; Ragan, Mark A.; Khanna, Kum Kum

    2014-01-01

    DNA-damage response machinery is crucial to maintain the genomic integrity of cells, by enabling effective repair of even highly lethal lesions such as DNA double-strand breaks (DSBs). Defects in specific genes acquired through mutations, copy-number alterations or epigenetic changes can alter the balance of these pathways, triggering cancerous potential in cells. Selective killing of cancer cells by sensitizing them to further DNA damage, especially by induction of DSBs, therefore requires careful modulation of DSB-repair pathways. Here, we review the latest knowledge on the two DSB-repair pathways, homologous recombination and non-homologous end joining in human, describing in detail the functions of their components and the key mechanisms contributing to the repair. Such an in-depth characterization of these pathways enables a more mechanistic understanding of how cells respond to therapies, and suggests molecules and processes that can be explored as potential therapeutic targets. One such avenue that has shown immense promise is via the exploitation of synthetic lethal relationships, for which the BRCA1–PARP1 relationship is particularly notable. Here, we describe how this relationship functions and the manner in which cancer cells acquire therapy resistance by restoring their DSB repair potential. PMID:24792170

  3. The TRACTISS Protocol: a randomised double blind placebo controlled clinical TRial of Anti-B-Cell Therapy In patients with primary Sjögren’s Syndrome

    PubMed Central

    2014-01-01

    Background Primary Sjögren’s Syndrome (PSS) mainly affects women (9:1 female:male ratio) and is one of the commonest autoimmune diseases with a prevalence of 0.1 – 0.6% of adult women. For patients with PSS there is currently no effective therapy that can alter the progression of the disease. The aim of the TRACTISS study is to establish whether in patients with PSS, treatment with rituximab improves clinical outcomes. Methods/design TRACTISS is a UK multi-centre, double-blind, randomised, controlled, parallel group trial of 110 patients with PSS. Patients will be randomised on a 1:1 basis to receive two courses of either rituximab or placebo infusion in addition to standard therapy, and will be followed up for up to 48 weeks. The primary objective is to assess the extent to which rituximab improves symptoms of fatigue and oral dryness. Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow, patient quality of life, measures of disease damage and disease activity, serological and peripheral blood biomarkers, and glandular histology and composition. Discussion The TRACTISS trial will provide direct evidence as to whether rituximab in patients with PSS leads to an improvement in patient symptoms and a reduction in disease damage and activity. Trial registration UKCRN Portfolio ID: 9809 ISRCTN65360827. PMID:24438039

  4. The JNC 7 approach compared to conventional treatment in diabetic patients with hypertension: a double-blind trial of initial monotherapy vs. combination therapy.

    PubMed

    Fox, Jonathan C; Leight, Kellie; Sutradhar, Santosh C; Demopoulos, Laura A; Gleim, Gilbert W; Lewin, Andrew J; Bakris, George L

    2004-08-01

    The JNC 7 states that persons with blood pressure (BP) more than 20/10 mm Hg above goal should be started on combination drug therapy. This criterion includes patients with BP >160/100 mm Hg and diabetics with hypertension. The goal BP for persons with diabetes mellitus is <130/80 mm Hg. A randomized, double-blind trial force titrated initial combination therapy utilizing an angiotensin receptor blocker (ARB) combination (losartan/hydrochlorothiazide [LOS/HCTZ]) compared with an angiotensin-converting enzyme (ACE) inhibitor (ramipril), for 8 weeks, and tested the hypothesis that combination therapy is more likely to achieve goal BP vs. monotherapy. At 4 weeks, 30.5% of LOS/HCTZ and 14.4% of ramipril recipients achieved goal diastolic BP (p<0.001). More participants achieved goal systolic BP in the ARB/HCTZ group at 4 weeks (29.8% vs. 14.4%; p<0.001). At 4 weeks, mean diastolic BP had decreased 10.2+/-7.4 mm Hg in the LOS/HCTZ group compared with 6.4+/-6.8 mm Hg in the ramipril group (p<0.001), and systolic BP had fallen 15.4+/-13.1 mm Hg in the ARB/HCTZ compared with 9.2+/-10.2 mm Hg in the ACE-inhibitor group (p<0.001). Significant differences favoring the combination were also noted at 8 weeks. Drug-related adverse experiences were 10.3% for the combination compared with 12.7% for the monotherapy group. Initial combination therapy with an ARB/HCTZ was more effective than ACE-inhibitor monotherapy in achieving BP goals in participants with diabetes with no significant differences in the incidence of adverse experiences. These observations confirm other studies of combination therapies, such as b blocker/diuretic, ACE inhibitor/diuretic, or ACE inhibitor/calcium channel blocker. The use of two medications will achieve goal BP in more patients than monotherapy. This observation is important in treatment of high-risk patients with diabetes. PMID:15308882

  5. Evaluating the Role of Corticosteroid Pulse Therapy in Patients With Secondary Progressive Multiple Sclerosis Receiving Mitoxantrone: A Double Blind Randomized Controlled Clinical Trial

    PubMed Central

    Rahimdel, Abolghasem; Zeinali, Ahmad; Mellat, Ali

    2015-01-01

    Background: Multiple sclerosis (MS) is a central nervous system disorder with periods of recurrence and recovery. Mitoxantrone has been approved for secondary progressive MS (SPMS) treatment but data lacks the role of corticosteroid pulse therapy in SPMS. Objectives: To evaluate the role of corticosteroid pulse therapy in patients with SPMS receiving mitoxantrone. Patients and Methods: A double blind randomized controlled clinical trial was performed on 71 patients with SPMS referred to Shahid Sadoughi Hospital (Yazd, Iran) for receiving mitoxantrone in two groups. The first group (35 patients) received 20 mg mitoxantrone plus 500 mg methylprednisolone monthly for six months. The second group (36 patients) received the same dosage of mitoxantrone plus 100 CC of 5% dextrose water monthly for six months. Expanded disability status scale (EDSS), MRI plaques in both groups before and after the treatment completion and six months after the end of trial were compared together. Results: 28 men and 43 women enrolled in the study. MRI plaques number reduced in groups significantly (2.29 vs. 2.17) without significant difference between the groups (P = 0.782). Six months after trial completion, plaques number increased in groups without significantly difference (0.72 vs. 0.77, P = 0.611). The mean value of EDSS showed significant reduction at the end of treatment in groups (0.79 and 0.53) without significant difference between the groups (P = 0.953). Six months after trial completion, EDSS increased in groups without significant difference (0.35 vs. 0.43, P = 0.624). Conclusions: Corticosteroid pulse therapy in SPMS was effective in inflammatory process, but could not postpone or decline the neurodegenerative process and besides the imposing side effects could not result in significant improvement in EDSS and MRI plaques number in long term. PMID:26566454

  6. Impact comparison of ketamine and sodium thiopental on anesthesia during electroconvulsive therapy in major depression patients with drug-resistant; a double-blind randomized clinical trial

    PubMed Central

    Salehi, B.; Mohammadbeigi, A.; Kamali, A. R.; Taheri-Nejad, M. R.; Moshiri, I.

    2015-01-01

    Background: Electroconvulsive therapy (ECT) is one of the available and the most effective therapies for the treatment of resistant depression. Considering the crucial role of seizure duration on therapeutic response in patients treated with ECT, this study aimed to compare the effect of ketamine and sodium thiopental anesthesia during ECT for treatment of patients with drug-resistant major depression (DRMD). Materials and Methods: In a double-blind randomized clinical trial, 160 patients with DRMD were selected consequently and were assigned randomly into two groups including ketamine 0.8 mg/kg and sodium thiopental 1.5 mg/kg. The seizure duration, recovery time, and the side effects of anesthesia were evaluated after 1-h after anesthesia. Data of recovery time and complication collected in 2nd, 4th, 6th, and 8th ECT. Depression was assessed by Hamilton depression scale. Results: The results indicated that ketamine and sodium thiopental had a significant effect on the reduction of depression scores in patients with DRMD (P < 0.05). Complications such as a headache, nausea, pain at the injection site, short-term delirium, and long-term delirium were higher in ketamine group (P > 0.05). But ketamine was more effective in improvement of depression score and increasing systolic and diastolic blood pressure (P < 0.05). The mean of seizure duration showed a decreasing trend and was significant between two study groups (P < 0.05). Conclusion: Anesthesia induced by ketamine during ECT therapy increased blood pressure and seizure duration. Therefore, due to lower medical complication and attack rate of seizure, ketamine is an appropriate option for anesthesia with ECT in patients with DRMD. PMID:26440233

  7. Comparison of hybrid volumetric modulated arc therapy (VMAT) technique and double arc VMAT technique in the treatment of prostate cancer

    PubMed Central

    Amaloo, Christopher; Nazareth, Daryl P.; Kumaraswamy, Lalith K.

    2015-01-01

    Background Volumetric modulated arc therapy (VMAT) has quickly become accepted as standard of care for the treatment of prostate cancer based on studies showing it is able to provide faster delivery with adequate target coverage and reduced monitor units while maintaining organ at risk (OAR) sparing. This study aims to demonstrate the potential to increase dose conformality with increased planner control and OAR sparing using a hybrid treatment technique compared to VMAT. Methods Eleven patients having been previously treated for prostate cancer with VMAT techniques were replanned with a hybrid technique on Varian Treatment Planning System. Multiple static IMRT fields (2 to 3) were planned initially based on critical OAR to reduce dose but provide some planning treatment volume (PTV) coverage. This was used as a base dose plan to provide 30–35% coverage for a single arc VMAT plan. Results The clinical VMAT plan was used as a control for the purposes of comparison. Average of all OAR sparing between the hybrid technique and VMAT showed the hybrid plan delivering less dose in almost all cases except for V80 of the bladder and maximum dose to right femoral head. PTV coverage was superior with the VMAT technique. Monitor unit differences varied, with the hybrid plan able to deliver fewer units 37% of the time, similar results 18% of the time, and higher units 45% of the time. On average, the hybrid plan delivered 10% more monitor units. Conclusions The hybrid plan can be delivered in a single gantry rotation combining aspects of VMAT with regions of dynamic intensity modulated radiation therapy (IMRT) within the treatment arc. PMID:26401136

  8. Azithromycin therapy of papillomatosis in dogs: a prospective, randomized, double-blinded, placebo-controlled clinical trial.

    PubMed

    Yağci, Buğrahan Bekir; Ural, Kerem; Ocal, Naci; Haydardedeoğlu, Ali Evren

    2008-08-01

    Azithromycin, an azalide subclass macrolide antibiotic, is an effective, well-tolerated and safe therapeutic option for treatment of papillomatosis in humans. This study reports the clinical and histopathological results from a prospective, randomized, double-blinded, placebo-controlled trial of 17 dogs of various breeds with diagnosis of oral (n = 12) and cutaneous papillomatosis (n = 5) treated with azithromycin. Papillomas appeared as whitish, verrucous, hyperkeratotic papules 1-2.7 mm in size. The cases were randomly assigned to azithromycin (n = 10) and placebo treatment groups (n = 7). Both owners and investigators were blinded to the allocation to the groups. Azithromycin (10 mg/kg) was administered per os every 24 h for 10 days. Clinical evaluations were done by the same investigator throughout the trial. Azithromycin treatment significantly decreased clinical scores (P < 0.001), whereas there was no change seen in the placebo group. In the azithromycin treatment group, skin lesions disappeared in 10-15 days. One case in the placebo had spontaneous regression of its papillomas by day 41, but lesions were still evident at day 50 in the remaining six cases. There was no recurrence of papillomatosis in the azithromycin treated dogs (follow up 8 months). No adverse effects were seen in either group. In conclusion, azithromycin appears to be a safe and effective treatment for canine papillomatosis. PMID:18494759

  9. Neutron production from beam-modifying devices in a modern double scattering proton therapy beam delivery system

    PubMed Central

    Pérez-Andújar, Angélica; Newhauser, Wayne D; DeLuca, Paul M

    2014-01-01

    In this work the neutron production in a passive beam delivery system was investigated. Secondary particles including neutrons are created as the proton beam interacts with beam shaping devices in the treatment head. Stray neutron exposure to the whole body may increase the risk that the patient develops a radiogenic cancer years or decades after radiotherapy. We simulated a passive proton beam delivery system with double scattering technology to determine the neutron production and energy distribution at 200 MeV proton energy. Specifically, we studied the neutron absorbed dose per therapeutic absorbed dose, the neutron absorbed dose per source particle and the neutron energy spectrum at various locations around the nozzle. We also investigated the neutron production along the nozzle's central axis. The absorbed doses and neutron spectra were simulated with the MCNPX Monte Carlo code. The simulations revealed that the range modulation wheel (RMW) is the most intense neutron source of any of the beam spreading devices within the nozzle. This finding suggests that it may be helpful to refine the design of the RMW assembly, e.g., by adding local shielding, to suppress neutron-induced damage to components in the nozzle and to reduce the shielding thickness of the treatment vault. The simulations also revealed that the neutron dose to the patient is predominated by neutrons produced in the field defining collimator assembly, located just upstream of the patient. PMID:19147903

  10. Neutron production from beam-modifying devices in a modern double scattering proton therapy beam delivery system.

    PubMed

    Pérez-Andújar, Angélica; Newhauser, Wayne D; Deluca, Paul M

    2009-02-21

    In this work the neutron production in a passive beam delivery system was investigated. Secondary particles including neutrons are created as the proton beam interacts with beam shaping devices in the treatment head. Stray neutron exposure to the whole body may increase the risk that the patient develops a radiogenic cancer years or decades after radiotherapy. We simulated a passive proton beam delivery system with double scattering technology to determine the neutron production and energy distribution at 200 MeV proton energy. Specifically, we studied the neutron absorbed dose per therapeutic absorbed dose, the neutron absorbed dose per source particle and the neutron energy spectrum at various locations around the nozzle. We also investigated the neutron production along the nozzle's central axis. The absorbed doses and neutron spectra were simulated with the MCNPX Monte Carlo code. The simulations revealed that the range modulation wheel (RMW) is the most intense neutron source of any of the beam spreading devices within the nozzle. This finding suggests that it may be helpful to refine the design of the RMW assembly, e.g., by adding local shielding, to suppress neutron-induced damage to components in the nozzle and to reduce the shielding thickness of the treatment vault. The simulations also revealed that the neutron dose to the patient is predominated by neutrons produced in the field defining collimator assembly, located just upstream of the patient. PMID:19147903

  11. Preventing Damage Limitation: Targeting DNA-PKcs and DNA Double-Strand Break Repair Pathways for Ovarian Cancer Therapy

    PubMed Central

    Dungl, Daniela A.; Maginn, Elaina N.; Stronach, Euan A.

    2015-01-01

    Platinum-based chemotherapy is the cornerstone of ovarian cancer treatment, and its efficacy is dependent on the generation of DNA damage, with subsequent induction of apoptosis. Inappropriate or aberrant activation of the DNA damage response network is associated with resistance to platinum, and defects in DNA repair pathways play critical roles in determining patient response to chemotherapy. In ovarian cancer, tumor cell defects in homologous recombination – a repair pathway activated in response to double-strand DNA breaks (DSB) – are most commonly associated with platinum-sensitive disease. However, despite initial sensitivity, the emergence of resistance is frequent. Here, we review strategies for directly interfering with DNA repair pathways, with particular focus on direct inhibition of non-homologous end joining (NHEJ), another DSB repair pathway. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a core component of NHEJ and it has shown considerable promise as a chemosensitization target in numerous cancer types, including ovarian cancer where it functions to promote platinum-induced survival signaling, via AKT activation. The development of pharmacological inhibitors of DNA-PKcs is on-going, and clinic-ready agents offer real hope to patients with chemoresistant disease. PMID:26579492

  12. Daylight photodynamic therapy with 1.5% 3-butenyl 5-aminolevulinate gel as a convenient, effective and safe therapy in acne treatment: A double-blind randomized controlled trial.

    PubMed

    Kwon, Hyuck Hoon; Moon, Ki Rang; Park, Seon Yong; Yoon, Ji Young; Suh, Dae Hun; Lee, Jee Bum

    2016-05-01

    While daylight photodynamic therapy (PDT) is a simpler and more tolerable treatment procedure for both clinicians and patients, it has never been applied for acne treatment. In this study, we evaluated efficacy, safety and histological changes of facial acne after application of the novel variant of 5-aminolevulinate (ALA)-ester, 1.5% 3-butenyl ALA-bu gel, using daylight only as the potential visible light source. Forty-six acne patients were randomly assigned to either ALA-bu or vehicle application group in a double-blind fashion. Both groups applied the allocated gel to facial acne lesions every other day for 12 weeks. At the final 12 week, both inflammatory and non-inflammatory acne lesions had decreased significantly by 58.0% and 34.1% in the ALA-bu group, respectively. Only a few patients expressed mild adverse effects. In the histopathological analysis, attenuated inflammatory cell infiltrations were observed and immunostaining intensities for interleukin-8, interleukin-1β, matrix metalloproteinase-9 and phosphorylated nuclear factor-κB were reduced concomitantly. Changes of their mRNA expression demonstrated comparable patterns. In conclusion, this ambulatory PDT was effective, very well tolerated and convenient for treating inflammatory acne lesions. Experimental results correlated well with clinical results. This novel regimen would provide a viable option for acne therapy. PMID:26660491

  13. Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial

    PubMed Central

    Yatham, L N; Beaulieu, S; Schaffer, A; Kauer-Sant'Anna, M; Kapczinski, F; Lafer, B; Sharma, V; Parikh, S V; Daigneault, A; Qian, H; Bond, D J; Silverstone, P H; Walji, N; Milev, R; Baruch, P; da Cunha, A; Quevedo, J; Dias, R; Kunz, M; Young, L T; Lam, R W; Wong, H

    2016-01-01

    Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder (n=159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry (‘0-weeks' group) or (ii) at 24 weeks after entry (‘24-weeks' group) or (iii) continuation of risperidone or olanzapine for the full duration of the study (‘52-weeks' group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, sub-group analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains

  14. Sildenafil citrate as a medical expulsive therapy for distal ureteric stones: A randomised double-blind placebo-controlled study

    PubMed Central

    Shokeir, Ahmed A.; Tharwat, Mohamed A.; Abolazm, Ahmed Elhussein; Harraz, Ahmed

    2016-01-01

    Objective To study the effect of sildenafil citrate on spontaneous passage of distal ureteric stones (DUS). Patients and methods This was a randomised double-blinded placebo-controlled study of 100 patients with DUS. Inclusion criteria were: male, age 18–65 years, normal renal function, and a single radiopaque unilateral DUS of 5–10 mm. Patients were randomly allocated into two equal groups, one that received placebo and the other that received 50 mg sildenafil citrate once daily. Both investigators and patients were masked to the type of treatment. Patients self-administered the medication until spontaneous passage of the DUS. In patients where there was uncontrolled pain, fever, an increase in serum creatinine of >1.8 mg/dL, progressive hydronephrosis or no further progress after 4 weeks, a decision was taken for further treatment. Results In all, 47 and 49 patients were available for analysis in both the placebo and sildenafil citrate groups; respectively. Both groups were comparable for age and stone characteristics. Spontaneous expulsion occurred in 19 of 47 patients (40.4%) in the placebo group and in 33 of 49 (67.3%) in the sildenafil citrate group (P = 0.014). The mean time to stone expulsion was significantly shorter in the sildenafil citrate group (P < 0.001). A multivariable Cox proportional hazards model showed that receiving sildenafil citrate was the only independent factor that had a significant impact on stone passage with a hazard ratio of 2.7 (95% confidence interval 1.5–4.8; P < 0.001). Conclusion Sildenafil citrate enhances spontaneous passage of 5–10 mm DUS. PMID:26966585

  15. Randomized Double-Blind Placebo-Controlled Trial of Bevacizumab Therapy for Radiation Necrosis of the Central Nervous System

    SciTech Connect

    Levin, Victor A.; Bidaut, Luc; Hou, Ping; Kumar, Ashok J.; Wefel, Jeffrey S.; Bekele, B. Nebiyou; Prabhu, Sujit; Loghin, Monica; Gilbert, Mark R.; Jackson, Edward F.

    2011-04-01

    Purpose: To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials: A total of 14 patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis. All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs. Eligible patients had undergone irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma. Patients were randomized to receive intravenous saline or bevacizumab at 3-week intervals. The magnetic resonance imaging findings 3 weeks after the second treatment and clinical signs and symptoms defined the response or progression. Results: The volumes of necrosis estimated on T{sub 2}-weighted fluid-attenuated inversion recovery and T{sub 1}-weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded (0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7 crossover) with decreases in T{sub 2}-weighted fluid-attenuated inversion recovery and T{sub 1}-weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant. All bevacizumab-treated patients-and none of the placebo-treated patients-showed improvement in neurologic symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses, only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis; one patient received a single additional dose of bevacizumab and the other patient received two doses. Conclusion: The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with

  16. The nociceptive and anti-nociceptive effects of bee venom injection and therapy: A double-edged sword

    PubMed Central

    Chen, Jun; Lariviere, William R.

    2010-01-01

    Bee venom injection as a therapy, like many other complementary and alternative medicine approaches, has been used for thousands of years to attempt to alleviate a range of diseases including arthritis. More recently, additional theraupeutic goals have been added to the list of diseases making this a critical time to evaluate the evidence for the beneficial and adverse effects of bee venom injection. Although reports of pain reduction (analgesic and antinociceptive) and anti-inflammatory effects of bee venom injection are accumulating in the literature, it is common knowledge that bee venom stings are painful and produce inflammation. In addition, a significant number of studies have been performed in the past decade highlighting that injection of bee venom and components of bee venom produce significant signs of pain or nociception, inflammation and many effects at multiple levels of immediate, acute and prolonged pain processes. This report reviews the extensive new data regarding the deleterious effects of bee venom injection in people and animals, our current understanding of the responsible underlying mechanisms and critical venom components, and provides a critical evaluation of reports of the beneficial effects of bee venom injection in people and animals and the proposed underlying mechanisms. Although further studies are required to make firm conclusions, therapeutic bee venom injection may be beneficial for some patients, but may also be harmful. This report highlights key patterns of results, critical shortcomings, and essential areas requiring further study. PMID:20558236

  17. A facile synthesis of strong near infrared fluorescent layered double hydroxide nanovehicles with an anticancer drug for tumor optical imaging and therapy

    NASA Astrophysics Data System (ADS)

    Chen, Chunping; Yee, Lee Kim; Gong, Hua; Zhang, Yong; Xu, Rong

    2013-05-01

    In this work, a new multifunctional nanovehicle for tumor optical imaging and therapy was developed using Y2O3:Er3+,Yb3+ nanoparticles as near infrared fluorescent nanophosphors, and MgAl-layered double hydroxide (LDH) nanosheets as anticancer drug nanovehicles. Monodispersed Y2O3:Er3+,Yb3+ nanophosphors were readily synthesized by the urea assisted homogenous precipitation method. Hierarchically structured LDH nanosheets intercalated with an anticancer drug, fluorouracil (5FU), were deposited on the surface of Y2O3:Er3+,Yb3+@SiO2 by a simple precipitation method followed by hydrothermal treatment. The resultant Y2O3:Er3+,Yb3+@SiO2@LDH-5FU nanovehicles exhibit strong red upconversion fluorescence under the excitation of a 980 nm laser, which allows tracking of the nanovehicles after localization in cancer cells. A better anticancer efficiency was obtained over the nanovehicles than the free drug which can be attributed to their positively charged surfaces for favorable interaction with the negatively charged cell membranes. The multifunctional nanovehicles designed in this work are expected to be promising material candidates for simultaneous tumor optical imaging and therapy.In this work, a new multifunctional nanovehicle for tumor optical imaging and therapy was developed using Y2O3:Er3+,Yb3+ nanoparticles as near infrared fluorescent nanophosphors, and MgAl-layered double hydroxide (LDH) nanosheets as anticancer drug nanovehicles. Monodispersed Y2O3:Er3+,Yb3+ nanophosphors were readily synthesized by the urea assisted homogenous precipitation method. Hierarchically structured LDH nanosheets intercalated with an anticancer drug, fluorouracil (5FU), were deposited on the surface of Y2O3:Er3+,Yb3+@SiO2 by a simple precipitation method followed by hydrothermal treatment. The resultant Y2O3:Er3+,Yb3+@SiO2@LDH-5FU nanovehicles exhibit strong red upconversion fluorescence under the excitation of a 980 nm laser, which allows tracking of the nanovehicles after

  18. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial

    PubMed Central

    Garcia, Hector H; Gonzales, Isidro; Lescano, Andres G; Bustos, Javier A; Zimic, Mirko; Escalante, Diego; Saavedra, Herbert; Gavidia, Martin; Rodriguez, Lourdes; Najar, Enrique; Umeres, Hugo; Pretell, E Javier

    2014-01-01

    Summary Background Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures. We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations. Methods In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (22·5 mg/kg per day). Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285. Findings Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 1·75, 95% CI 1·10–2·79, p=0·014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 1·44, 95% CI 0·87–2·38, p=0·151

  19. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol

    PubMed Central

    Gulati, Geeta; Heck, Siri Lagethon; Ree, Anne Hansen; Hoffmann, Pavel; Schulz-Menger, Jeanette; Fagerland, Morten W.; Gravdehaug, Berit; von Knobelsdorff-Brenkenhoff, Florian; Bratland, Åse; Storås, Tryggve H.; Hagve, Tor-Arne; Røsjø, Helge; Steine, Kjetil; Geisler, Jürgen; Omland, Torbjørn

    2016-01-01

    Aims Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. Methods and results In a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the β-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI −0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. Conclusion In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function. PMID:26903532

  20. Effect of low-level laser therapy in the treatment of cochlear tinnitus: a double-blind, placebo-controlled study.

    PubMed

    Dehkordi, Mahboobeh Adami; Einolghozati, Sasan; Ghasemi, Seyyed Mohsen; Abolbashari, Samaneh; Meshkat, Mojtaba; Behzad, Hadi

    2015-01-01

    Many treatments for chronic tinnitus have been attempted, but the condition remains difficult to cure, especially in the case of cochlear tinnitus. We conducted a prospective, double-blind, placebo-controlled study to assess the effect of low-dose laser therapy on chronic cochlear tinnitus. Our study population was made up of 66 patients-33 who received active laser treatment (case group) and 33 who received inactive dummy treatment (control group). Patients in the laser group received 5 mV with a wavelength of 650 nm for 20 minutes a day, 5 days a week, for 4 weeks. The controls followed the same schedule, but they were "treated" with an inactive device. The degree of tinnitus was evaluated before and after treatment in each group in three ways: (1) the Tinnitus Severity Index (TSI), (2) a subjective 10-point self-assessment scale for tinnitus loudness, and (3) the Tinnitus Evaluation Test (TET). At study's end, we found no statistically significant differences between the case and control groups in the number of patients who experienced a reduction in TSI values (p = 0.589) or a reduction in subjective self-assessment scores (p = 0.475). Nor did we find any significant reductions in the loudness (p = 0.665) and frequency (p = 0.396) of tinnitus as determined by the TET. We conclude that 5-mV laser therapy with a wavelength of 650 nm is no better than placebo for improving hearing thresholds overall or for treating tinnitus with regard to age, sex, environmental noise level, and the duration of tinnitus. PMID:25606834

  1. The Efficacy of Shugan Jianpi Zhixie Therapy for Diarrhea-Predominant Irritable Bowel Syndrome: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

    PubMed Central

    Sun, Xiaomin; Tang, Yang; Cheng, Jingru; Wang, Tian; Li, Fei; Kuang, Yuxiang; Luo, Ren; Zhao, Xiaoshan

    2015-01-01

    Background Shugan Jianpi Zhixie therapy (SJZT) has been widely used to treat diarrhea-predominant irritable bowel syndrome (IBS-D), but the results are still controversial. A meta-analysis of randomized, double-blind, placebo-controlled trials was performed to assess the efficacy and tolerability of SJZT for IBS-D. Methods The MEDLINE, EMBASE, Cochrane Library, the China National Knowledge Infrastructure database, the Chinese Biomedical Literature database and the Wanfang database were searched up to June 2014 with no language restrictions. Summary estimates, including 95% confidence intervals (CI), were calculated for global symptom improvement, abdominal pain improvement, and Symptom Severity Scale (BSS) score. Results Seven trials (N=954) were included. The overall risk of bias assessment was low. SJZT showed significant improvement for global symptom compared to placebo (RR 1.61; 95% CI 1.24, 2.10; P =0.0004; therapeutic gain = 33.0%; number needed to treat (NNT) = 3.0). SJZT was significantly more likely to reduce overall BSS score (SMD –0.67; 95% CI –0.94, –0.40; P < 0.00001) and improve abdominal pain (RR 4.34; 95% CI 2.64, 7.14; P < 0.00001) than placebo. The adverse events of SJZT were no different from those of placebo. Conclusions This meta-analysis suggests that SJZT is an effective and safe therapy option for patients with IBS-D. However, due to the high clinical heterogeneity and small sample size of the included trials, further standardized preparation, large-scale and rigorously designed trials are needed. PMID:25853241

  2. Cost-effectiveness analysis of low density lipoprotein cholesterol-lowering therapy in hypertensive patients with type 2 diabetes in Korea: single-pill regimen (amlodipine/atorvastatin) versus double-pill regimen (amlodipine+atorvastatin)

    PubMed Central

    Park, Ji-Hyun; Lee, Yong-Ho; Ko, Su-Kyoung; Cha, Bong-Soo

    2015-01-01

    OBJECTIVES: Single-pill combination therapy (amlodipine/atorvastatin) might be more effective than double-pill therapy (amlodipine+atorvastatin) in patients with diabetes and concomitant hypertension requiring statin therapy. We compared the cost-effectiveness of a single-pill with that of double-pill for control of low density lipoprotein cholesterol (LDL-C) levels, with the ultimate goal of cardiovascular disease prevention, in these patients using a cost-effectiveness analysis model that considered medication adherence. METHODS: Effectiveness was defined as the percentage (%) attainment of target LDL-C levels (<100 mg/dL) based on adherence for each therapy. Adherence was defined as compliance to medication (≥80% proportion of days covered). A systematic review of the literature was conducted to determine the proportion of patients who were adherent and target goal attainment based on adherence level. The annual medication costs were based on the adherence levels for each regimen. The average cost-effectiveness ratio (ACER) was calculated as the cost per % attainment of the target LDL-C level. RESULTS: The ACER for the single-pill regimen was lower than for the double-pill regimen (4,123 vs. 6,062 Korean won per 1% achievement of target goal). Compared with the double-pill, the medication costs were approximately 32% lower with the single-pill. CONCLUSION: A single-pill for reductions in LDL-C is cost-effective compared with double-pill in hypertensive patients with type 2 diabetes. PMID:25773438

  3. Efficacy of Zinc Sulfate as an Add-on Therapy to Risperidone Versus Risperidone Alone in Patients With Schizophrenia: A Double-Blind Randomized Placebo-Controlled Trial

    PubMed Central

    Mortazavi, Mehran; Farzin, Davood; Zarhghami, Mehran; Hosseini, Seyed Hamzeh; Mansoori, Parisa; Nateghi, Gholamreza

    2015-01-01

    Background: Zinc can modulate fast-excitatory transmission, facilitate the release of amino butyric acid and potentiate nicotinic acetylcholine receptors. There are also emerging evidences discussing the implication of these neurotransmitters in pathophysiology of schizophrenia. Objectives: The purpose of this study was to evaluate the efficacy of Zn sulfate as an add-on therapy in the treatment of schizophrenia in a 6-week, double-blind and placebo-controlled trial. Patients and Methods: Eligible participants were 30 inpatients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Patients were randomly allocated into two equal groups; one group of patients received risperidone 6 mg/day plus capsules of Zn sulfate (each containing 50 mg elemental Zn) three times a day and another group received risperidone 6 mg/day plus placebo. The Positive and Negative Syndrome Scale (PANSS) was applied to assess the psychotic symptoms and aggression risk at baseline, week 2, 4, and 6 of the study. Results: The results of this study showed that both protocols significantly decreased the scores on all subscales of the PANSS and supplemental aggression risk subscale as well as PANSS total score over the study. However, this improvement was significantly higher in Zn sulfate receiving group compared to the placebo group. No major clinical side-effects were detected. Conclusions: It may be concluded that Zn is an effective adjuvant agent in the management of patients with schizophrenia. PMID:26576178

  4. [A Case of Double Cancer of Initially Unresectable Sigmoid Colon Cancer and Advanced Gastric Cancer Treated with Curative Resection after mFOLFOX6 Therapy].

    PubMed

    Yoshikawa, Toru; Aoki, Kazunori; Mitsuhashi, Yuto; Tomiura, Satoko; Suto, Akiko; Miura, Takuya; Ikenaga, Shojirokazunori; Shibasaki, Itaru; Endo, Masaaki

    2016-03-01

    A 61-year-old man was admitted to our hospital because of a complaint of blood in stool. He was diagnosed with advanced colon and gastric cancers. Computed tomography (CT) revealed a sigmoid tumor with invasion to the bladder, a metastatic tumor in the lateral segmental branch of the left hepatic lobe, and ascites. He was diagnosed with initially unresectable double cancer. Ileostomy was performed immediately, and he was treated with modified (m) FOLFOX6 regimen (oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin). After 6 courses of the mFOLFOX6 regimen, CT revealed that the primary lesion of the sigmoid colon and liver metastasis had reduced in size, and the ascites had disappeared. Gastroscopy revealed that the gastric cancer had disappeared. Biopsy results were negative. Accordingly, his gastric cancer was diagnosed as treatment effect Grade 3. After 8 courses of mFOLFOX6 therapy, sigmoidectomy, partial resection of the bladder, and partial resection of the liver were performed. Gastric cancer was not resected in accordance with his will. Although 40 months has passed after the radical resection, neither the sigmoid colon cancer nor the gastric cancer recurred. PMID:27067857

  5. Clinical effects of topical antifungal therapy in chronic rhinosinusitis: a randomized, double-blind, placebo-controlled trial of intranasal fluconazole

    PubMed Central

    Hashemian, Farshad; Hashemian, Farnaz; Molaali, Najmeh; Rouini, Mohammadreza; Roohi, Elnaz; Torabian, Saadat

    2016-01-01

    Several studies have been in favor of fungi as a possible pathogenesis of chronic rhinosinusitis (CRS); however, to date, there is no scientific consensus about the use of antifungal agents in disease management. The aim of the present study was to investigate the efficacy of intranasal fluconazole in improving disease symptoms and objective outcomes of patients with CRS. A randomized, double-blind, placebo-controlled study was conducted on 54 patients who were diagnosed with CRS and had not been responsive to routine medical treatments. They were randomly assigned to receive either fluconazole nasal drop 0.2 % or placebo in addition to the standard regimen for a duration of 8 weeks. Patients' outcomes were evaluated according to Sino-Nasal Outcome Test 20 (SNOT-20), endoscopic scores, and Computed Tomography (CT) scores. No statistically significant difference was found in SNOT-20 (p = 0.201), endoscopic (p = 0.283), and CT scores (p = 0.212) of the patients at baseline and after 8-week course of treatment between drug and placebo group. Similar to many studies, the use of topical antifungal treatment for patients with CRS was not shown to be significantly effective. However, further studies are needed to obtain high levels of consistent evidence in order to arrive at a decision whether antifungal therapy is effective in management of CRS or not. PMID:27065776

  6. SHORT-TERM EFFICACY OF LOW-LEVEL LASER THERAPY IN PATIENTS WITH KNEE OSTEOARTHRITIS: A RANDOMIZED PLACEBO-CONTROLLED, DOUBLE-BLIND CLINICAL TRIAL

    PubMed Central

    Fukuda, Vanessa Ovanessian; Fukuda, Thiago Yukio; Guimarães, Márcio; Shiwa, Silvia; de Lima, Bianca Del Cor; Martins, Rodrigo Álvaro Brandão Lopes; Casarotto, Raquel Aparecida; Alfredo, Patrícia Pereira; Bjordal, Jan Magnus; Fucs, Patrícia Maria Moraes Barros

    2015-01-01

    Objective: This study was designed to evaluate the short-term efficacy of low-level laser therapy (LLLT) for improving pain and function in patients with knee osteoarthritis. Methods: Forty-seven patients with knee osteoarthritis (79 knees), of both genders, participated in this randomized controlled double-blind clinical trial. They were randomly allocated to two groups: laser group with 25 patients (41 knees) and placebo group with 22 patients (38 knees). LLLT was performed three times a week, totaling nine sessions, using a AsGa 904 nm laser with mean power of 60 mW and beam area of 0.5 cm2. Nine points were irradiated on the knee, with energy of 3.0 J/point. The placebo group was treated with the same laser device, but with a sealed probe. Evaluations using Lequesne, visual numerical scale (VNS), Timed Up and Go (TUG), goniometry and dynamometry were conducted before the treatment started and after the nine sessions of LLLT. Results: A significant improvement in pain and function was found in all the assessments applied to the laser group. On comparing the laser group with the placebo group, significant differences were found in the VNS-resting and Lequesne evaluations. Conclusion: Treatment with LLLT improves pain and function over the short term in patients with knee osteoarthritis. PMID:27027049

  7. The Effect of Omega-3 Fatty Acids in Patients With Active Rheumatoid Arthritis Receiving DMARDs Therapy: Double-Blind Randomized Controlled Trial

    PubMed Central

    Rajaei, Elham; Mowla, Karim; Ghorbani, Ali; Bahadoram, Sara; Bahadoram, Mohammad; Dargahi-Malamir, Mehrdad

    2016-01-01

    Background: Rheumatoid arthritis is a symmetric peripheral polyarthritis of unknown etiology that, untreated or if unresponsive the therapy, typically leads to deformity and destruction of joints due to erosion of cartilage and bone. Omega-3 fatty acids have been shown to reduce morning stiffness, the number of tender joints and swollen joints in patients with rheumatoid arthritis. This study is designed for evaluation of omega-3 effects on disease activity and remission of rheumatoid arthritis in DMARDs treated patients and on weight changes and reduction of analgesic drugs consumption versus placebo. Methods: Sixty patients with active rheumatoid arthritis (49 female and 11 male) underwent rheumatologist examination and disease activity score were calculated. Then patients were enrolled in this 12 week, double blind, randomized, placebo- controlled study. The patients in both groups continued their pre study standard treatment. The patients were visited every 4 weeks, 4 times and data were recorded. Results: Significant improvement in the patient’s global evaluation and in the physician’s assessment of disease was observed in those taking omega-3. The proportions of patients who improved and of those who were able to reduce their concomitant analgesic medication were significantly greater with omega-3 consumption. There were no weight changes. Conclusion: Daily supplementation with omega-3 results has significant clinical benefit and may reduce the need for concomitant analgesic consumption without weight changes. PMID:26925896

  8. Effect of low-level laser therapy on the post-surgical inflammatory process after third molar removal: study protocol for a double-blind randomized controlled trial

    PubMed Central

    2013-01-01

    determination of the actual effect of laser therapy on this model. The present study aims to provide a randomized, controlled, double-blind trial to compare four different LLLT parameters in relation to the outcomes of pain, swelling and muscle spasm following surgery for the extraction of impacted third molars and evaluate the effects os surgery on patients' quality os life (QOL). Trial registration Brazilian Registry of Clinical Trials - Rebec (RBR-6XSB5H). PMID:24195796

  9. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial

    PubMed Central

    Alton, Eric W F W; Armstrong, David K; Ashby, Deborah; Bayfield, Katie J; Bilton, Diana; Bloomfield, Emily V; Boyd, A Christopher; Brand, June; Buchan, Ruaridh; Calcedo, Roberto; Carvelli, Paula; Chan, Mario; Cheng, Seng H; Collie, D David S; Cunningham, Steve; Davidson, Heather E; Davies, Gwyneth; Davies, Jane C; Davies, Lee A; Dewar, Maria H; Doherty, Ann; Donovan, Jackie; Dwyer, Natalie S; Elgmati, Hala I; Featherstone, Rosanna F; Gavino, Jemyr; Gea-Sorli, Sabrina; Geddes, Duncan M; Gibson, James S R; Gill, Deborah R; Greening, Andrew P; Griesenbach, Uta; Hansell, David M; Harman, Katharine; Higgins, Tracy E; Hodges, Samantha L; Hyde, Stephen C; Hyndman, Laura; Innes, J Alastair; Jacob, Joseph; Jones, Nancy; Keogh, Brian F; Limberis, Maria P; Lloyd-Evans, Paul; Maclean, Alan W; Manvell, Michelle C; McCormick, Dominique; McGovern, Michael; McLachlan, Gerry; Meng, Cuixiang; Montero, M Angeles; Milligan, Hazel; Moyce, Laura J; Murray, Gordon D; Nicholson, Andrew G; Osadolor, Tina; Parra-Leiton, Javier; Porteous, David J; Pringle, Ian A; Punch, Emma K; Pytel, Kamila M; Quittner, Alexandra L; Rivellini, Gina; Saunders, Clare J; Scheule, Ronald K; Sheard, Sarah; Simmonds, Nicholas J; Smith, Keith; Smith, Stephen N; Soussi, Najwa; Soussi, Samia; Spearing, Emma J; Stevenson, Barbara J; Sumner-Jones, Stephanie G; Turkkila, Minna; Ureta, Rosa P; Waller, Michael D; Wasowicz, Marguerite Y; Wilson, James M; Wolstenholme-Hogg, Paul

    2015-01-01

    Summary Background Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. Methods We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50–90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene–liposome complex or 0·9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Findings Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3·7%, 95% CI 0·1–7·3; p=0·046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Interpretation Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of

  10. The effect of oscillating-energy manual therapy on lateral epicondylitis: a randomized, placebo-control, double-blinded study.

    PubMed

    Nourbakhsh, Mohammad Reza; Fearon, Frank J

    2008-01-01

    Symptoms of lateral epicondylitis (LE) are attributed to degenerative changes and inflammatory reactions in the common extensor tendon induced by microscopic tears in the tissue after repetitive or overload functions of the wrist and hand extensor muscles. Conventional treatments, provided on the premise of inflammatory basis of LE, have shown 39-80% failure rate. An alternative approach suggests that symptoms of LE could be due to active tender points developed in the origin of hand and wrist extensor muscles after overuse or repetitive movements. Oscillating-energy Manual Therapy (OEMT), also known as V-spread, is a craniosacral manual technique that has been clinically used for treating tender points over the suture lines in the skull. Considering symptoms of LE may result from active tender points, the purpose of this study was to investigate the effect of OEMT on pain, grip strength, and functional abilities of subjects with chronic LE. Twenty-three subjects with chronic LE (>3mo) between ages of 24 and 72 years participated in this study. Before their participation, all subjects were screened to rule out cervical and other pathologies that could possibly contribute to their lateral elbow pain. Subjects who met the inclusion criteria were randomized into treatment and placebo treatment groups by a second (treating) therapist. Subjects were blinded to their group assignment. Subjects in the treatment group received OEMT for six sessions. During each treatment session, first a tender point was located through palpation. After proper hand placement, the therapist focused the direction of the oscillating energy on the localized tender point. Subjects in the placebo group underwent the same procedure, but the direction of the oscillating energy was directed to an area above or below the tender points, not covering the affected area. Jamar Dynamometer, Patient Specific Functional Scale (PSFS), and Numeric Rating Scale (NRS) were used to measure grip strength

  11. A comparison study of metformin only therapy and metformin combined with Chinese medicine jianyutangkang therapy in patients with type 2 diabetes: A randomized placebo-controlled double-blind study.

    PubMed

    Hu, Yuan; Zhou, Xin; Liu, Ping; Wang, Bo; Duan, Dong-Mei; Guo, Dai-Hong

    2016-02-01

    The aim of this 26-week, double-blind, controlled clinical trial, was to compare the efficacy of monotherapy (metformin only) with combination therapy (Chinese medicine prescription JianYuTangKang [JYTK] plus metformin) on type 2 diabetes. All patients on metformin were randomized to receive authenticated JYTK (59 patients) or placebo JYTK (53 patients), 4.5g daily, for 26 weeks. Patients also received information regarding diet and exercise. Fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1C) level, and a lipid profile were measured before, during, and after the treatment. The results of the treatment group (JYTK plus metformin) were noninferior to those of the control group (metformin plus placebo) at 8 and 18 weeks. After 26 weeks of treatment, FPG levels decreased to 6.1±1.0mmol/L in the treatment group and 7.0±1.5mmol/L in the control group (p<0.01). HbA1C levels after 26 weeks were also significantly decreased in the treatment group compared with the control group (p<0.01). In addition, lipid profiles were also significantly different between the two groups. Integrated traditional Chinese and Western medicine therapy (JYTK plus metformin) for patients with type 2 diabetes mellitus may not only help improve glycemia and insulin sensitivity, but also help to modify the diabetes related lipid equilibrium. And thereby provides a basis for a novel, effective, and safe approach, to treat type 2 diabetic patients. PMID:26860796

  12. Randomized, Double-Blinded, Placebo-Controlled, Trial of Risedronate for the Prevention of Bone Mineral Density Loss in Nonmetastatic Prostate Cancer Patients Receiving Radiation Therapy Plus Androgen Deprivation Therapy

    SciTech Connect

    Choo, Richard; Lukka, Himu; Cheung, Patrick; Corbett, Tom; Briones-Urbina, Rosario; Vieth, Reinhold; Ehrlich, Lisa; Kiss, Alex; Danjoux, Cyril

    2013-04-01

    Purpose: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. Methods and Materials: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > −2.5 on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. Results: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. Conclusions: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT.

  13. Downregulation of Integrins in Cancer Cells and Anti-Platelet Properties Are Involved in Holothurian Glycosaminoglycan-Mediated Disruption of the Interaction of Cancer Cells and Platelets in Hematogenous Metastasis.

    PubMed

    Qian, Wenhui; Tao, Li; Wang, Yingyu; Zhang, Feng; Li, Mengqiu; Huang, Shile; Wang, Aiyun; Chen, Wenxing; Yue, Zhiqiang; Chen, Lei; Liu, Yuping; Huang, Chenhu; Zhang, Lei; Li, Yao; Lu, Yin

    2015-01-01

    Activated platelets have been recognized as an accessory character in the cascade of tumor hematogenous metastasis, and intervention of tumor cell attachment to the activated platelets or microemboli formation might be a leading strategy to prevent tumor cells surviving in the blood vessels and sequential metastasis. Recently, we have demonstrated that holothurian glycosaminoglycan (hGAG), a sulfated polysaccharide with potent anticoagulant activity extracted from the sea cucumber Holothuria leucospilota Brandt, was highly efficacious against tumor metastasis. In this study, we identified the potential effects of hGAG on the disruption of interactions of cancer cells and platelets and the underlying mechanisms, which were supported by the following evidence: hGAG (1) inhibited thrombin-induced platelet activation and aggregation, (2) reduced adhesion between platelet and breast cancer cells, and abrogated platelets/cancer cells adhering to fibrinogen, (3) attenuated platelet-cancer cell complex formation (the number and size of aggregates) and (4) suppressed both mRNA and protein levels of β1 and β3 integrins, matrix metalloproteinase (MMP)-2 and MMP-9, while increasing the expression of the MMP inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1 in MDA-MB-231 cells. These results suggested that both the antiplatelet properties and mitigation of the levels of cellular adhesion molecules contributed to the anticancer effects of hGAG, and might thus be exploited for clinical adjuvant therapy to attenuate tumor hematogenous metastasis. PMID:26488158

  14. Phase 1 Randomized, Double-Blind, Placebo-Controlled Study of RG7667, an Anticytomegalovirus Combination Monoclonal Antibody Therapy, in Healthy Adults

    PubMed Central

    Ishida, Julie H.; Burgess, Tracy; Derby, Michael A.; Brown, Pearline A.; Maia, Mauricio; Deng, Rong; Emu, Brinda; Feierbach, Becket; Fouts, Ashley E.; Liao, X. Charlene

    2015-01-01

    Cytomegalovirus can cause debilitating and life-threatening disease in newborns infected in utero and immunocompromised individuals, including transplant recipients. RG7667 is a unique combination of two monoclonal antibodies that binds glycoprotein complexes on the surface of cytomegalovirus and inhibits its entry into host cells. A phase 1 first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study of RG7667 given intravenously was conducted in 181 healthy adults. The study involved a single ascending dose stage (1, 3, 5, and 10 mg/kg each antibody; n = 21), a multiple ascending dose stage (5 and 10 mg/kg each antibody monthly for 3 doses; n = 10), and a multiple dose expansion stage (10 mg/kg each antibody monthly for 3 doses; n = 150). Subjects were followed for 85 to 141 days to evaluate safety, tolerability, pharmacokinetics, and immunogenicity. Most adverse events were mild, and the incidence of adverse events was similar among the RG7667 and placebo groups. RG7667 had dose-proportional pharmacokinetics in all three dosing stages, a mean terminal half-life of 20 to 30 days, and an overall pharmacokinetic profile consistent with that of a human monoclonal antibody that lacks endogenous host targets. The proportion of subjects developing an antitherapeutic antibody response was not higher in the RG7667 group than in the placebo group. In summary, single and multiple doses of RG7667 were found to be safe and well-tolerated in healthy adults and had a favorable pharmacokinetic and immunogenicity profile. This study supports further development of RG7667 as a therapy for the prevention and treatment of cytomegalovirus infection in susceptible populations. (This study has been registered at ClinicalTrials.gov under registration no. NCT01496755.) PMID:26055360

  15. Randomized Double-blind Placebo-controlled Trial of Celecoxib for Oral Mucositis in Patients Receiving Radiation Therapy for Head and Neck Cancer

    PubMed Central

    Lalla, Rajesh V.; Choquette, Linda E.; Curley, Kathleen F.; Dowsett, Robert J.; Feinn, Richard S.; Hegde, Upendra P.; Pilbeam, Carol C.; Salner, Andrew L.; Sonis, Stephen T.; Peterson, Douglas E.

    2016-01-01

    Objectives Oral mucositis (OM) is a painful complication of radiation therapy (RT) for head and neck cancer (H&NC). OM can compromise nutrition, require opioid analgesics and hospitalization for pain control, and lead to treatment interruptions. Based on the role of inflammatory pathways in OM pathogenesis, we investigated effect of cyclooxygenase-2 (COX-2) inhibition on severity and morbidity of OM. Methods In this double-blind placebo-controlled trial, 40 H&NC patients were randomized to daily use of 200 mg celecoxib or placebo, for the duration of RT. Clinical OM, normalcy of diet, pain scores, and analgesic use were assessed 2–3 times/week by blinded investigators during the 6–7 week RT period, using validated scales. Results Twenty subjects were randomized to each arm, which were similar with respect to tumor location, radiation dose, and concomitant chemotherapy. In both arms, mucositis and pain scores increased over course of RT. Intention-to-treat analyses demonstrated no significant difference in mean Oral Mucositis Assessment Scale (OMAS) scores at 5000 cGy (primary endpoint). There was also no difference between the two arms in mean OMAS scores over the period of RT, mean worst pain scores, mean normalcy of diet scores, or mean daily opioid medication use in IV morphine equivalents. There were no adverse events attributed to celecoxib use. Conclusions Daily use of a selective COX-2 inhibitor, during period of RT for H&NC, did not reduce the severity of clinical OM, pain, dietary compromise or use of opioid analgesics. These findings also have implications for celecoxib use in H&NC treatment regimens (NCT00698204). PMID:25151488

  16. AAV-Mediated Gene Therapy in the Guanylate Cyclase (RetGC1/RetGC2) Double Knockout Mouse Model of Leber Congenital Amaurosis

    PubMed Central

    Boye, Sanford L.; Peshenko, Igor V.; Huang, Wei Chieh; Min, Seok Hong; McDoom, Issam; Kay, Christine N.; Liu, Xuan; Dyka, Frank M.; Foster, Thomas C.; Umino, Yumiko; Karan, Sukanya; Jacobson, Samuel G.; Baehr, Wolfgang; Dizhoor, Alexander; Hauswirth, William W.

    2013-01-01

    Mutations in GUCY2D are associated with recessive Leber congenital amaurosis-1 (LCA1). GUCY2D encodes photoreceptor-specific, retinal guanylate cyclase-1 (RetGC1). Reports of retinal degeneration in LCA1 are conflicting; some describe no obvious degeneration and others report loss of both rods and cones. Proof of concept studies in models representing the spectrum of phenotypes is warranted. We have previously demonstrated adeno-associated virus (AAV)-mediated RetGC1 is therapeutic in GC1ko mice, a model exhibiting loss of cones only. The purpose of this study was to characterize AAV-mediated gene therapy in the RetGC1/RetGC2 double knockout (GCdko) mouse, a model lacking rod and cone function and exhibiting progressive loss of both photoreceptor subclasses. Use of this model also allowed for the evaluation of the functional efficiency of transgenic RetGC1 isozyme. Subretinal delivery of AAV8(Y733F) vector containing the human rhodopsin kinase (hGRK1) promoter driving murine Gucy2e was performed in GCdko mice at various postnatal time points. Treatment resulted in restoration of rod and cone function at all treatment ages and preservation of retinal structure in GCdko mice treated as late as 7 weeks of age. Functional gains and structural preservation were stable for at least 1 year. Treatment also conferred cortical- and subcortical-based visually-guided behavior. Functional efficiency of transgenic RetGC1 was indistinguishable from that of endogenous isozyme in congenic wild-type (WT) mice. This study clearly demonstrates AAV-mediated RetGC1 expression restores function to and preserves structure of rod and cone photoreceptors in a degenerative model of retinal guanylate cyclase deficiency, further supporting development of an AAV-based vector for treatment of LCA1. PMID:23210611

  17. Low level laser therapy associated with a strength training program on muscle performance in elderly women: a randomized double blind control study.

    PubMed

    Toma, Renata Luri; Vassão, Patrícia Gabrielli; Assis, Livia; Antunes, Hanna Karen Moreira; Renno, Ana Claudia Muniz

    2016-08-01

    The aging process leads to a gradual loss of muscle mass and muscle performance, leading to a higher functional dependence. Within this context, many studies have demonstrated the benefits of a combination of physical exercise and low level laser therapy (LLLT) as an intervention that enhances muscle performance in young people and athletes. The aim of this study was to evaluate the effects of combination of LLLT and strength training on muscle performance in elderly women. For this, a hundred elderly women were screened, and 48 met all inclusion criteria to participate in this double-blind placebo-controlled trial. Volunteers were divided in three groups: control (CG = 15), strength training associated with placebo LLLT (TG = 17), and strength training associated with active LLLT (808 nm, 100 mW, 7 J) (TLG = 16). The strength training consisted of knee flexion-extension performed with 80 % of 1-repetition maximum (1-RM) during 8 weeks. Several outcomes related to muscle performance were analyzed through the 6-min walk test (6-MWT), isokinetic dynamometry, surface electromyography (SEMG), lactate concentration, and 1-RM. The results revealed that a higher work (p = 0.0162), peak torque (p = 0.0309), and power (p = 0.0223) were observed in TLG compared to CG. Furthermore, both trained groups increased the 1-RM load (TG vs CG: p = 0.0067 and TLG vs CG: p < 0.0001) and decreased the lactate concentration in the third minute after isokinetic protocol (CG vs TLG: p = 0.0289 and CG vs TG: p = 0.0085). No difference in 6-MWT and in fatigue levels were observed among the groups. The present findings suggested that LLLT in combination with strength training was able to improve muscle performance in elderly people. PMID:27250715

  18. Effects of low-level laser therapy on performance, inflammatory markers, and muscle damage in young water polo athletes: a double-blind, randomized, placebo-controlled study.

    PubMed

    Zagatto, Alessandro Moura; de Paula Ramos, Solange; Nakamura, Fábio Yuzo; de Lira, Fábio Santos; Lopes-Martins, Rodrigo Álvaro Brandão; de Paiva Carvalho, Rodrigo Leal

    2016-04-01

    This study aimed to evaluate the effects of 5 days of 810-nm low-level laser therapy (LLLT) intervention on inflammatory and muscle damage markers and performance in young water polo players. Twenty young male water polo players participated in the study, which was designed as a randomized, double-blinded, placebo-controlled trial. Active LLLT or an identical placebo LLLT were delivered to eight points on the adductor muscle region immediately after each training day. Performance was measured by a 200-m maximal swimming (P200) and a 30-s crossbar jump test (30CJ) which was performed every day before training, and blood samples were drawn pre and post the final LLLT intervention to measure interleukins (IL) and muscle damage markers. There was no significant change in the P200 exercise in the LLLT group compared with the placebo group but there was a moderate improvement in the 30CJ (8.7 ± 2.6 %). IL-1β and tumor necrosis factor-alpha presented increased (P < 0.016) concentration within group 48 h after the last LLLT intervention compared to pre, 0, and 24 h, but did not differ between groups. IL-10 increased over time in the placebo group and reached a moderate effect compared to the LLLT group. The creatine kinase decreased significantly (P = 0.049) over the time within the LLLT treatment group, but there was no significant change in lactate dehydrogenase (P = 0.150). In conclusion, LLLT resulted in a non-significant, but small to moderate effect on inflammatory and muscle damage markers and a moderate effect on performance in water polo players. In addition, the lack of positive results could be due to the small area covered by irradiation and this should be considered in future studies. PMID:26873498

  19. Placebo-controlled, randomized double-blind clinical trial with Sinupret® sugar coated tablets on the basis of a therapy with antibiotics and decongestant nasal drops in acute sinusitis.

    PubMed

    Neubauer, N; März, R W

    1994-12-01

    On the basis of therapy with antibiotics and nasal decongestants the efficacy of an additional treatment with the herbal combination Sinupret containing gentian root, cowslip flowers, sour dock herbs, elder flowers and shop vervain wort herbs was assessed in a randomized, placebo-controlled double-blind clinical trial involving 160 patients with acute bacterial sinusitis. Primary outcome criteria were radiographic findings and patient assessment. Secondary variables were several clinical symptoms of sinusitis which served as indicators of the pharmacological profile. The results showed that, according to the radiographic findings and the patient assessments, therapy with antibiotic and decongestants achieved a significant improvement in the treatment group; changes in clinical signs showed good correlation with the radiographic findings and the patient assessments. Conventional therapy for acute bacterial sinusitis can be improved markedly by including Sinupret in the therapeutic regimen. PMID:23195935

  20. Ranolazine versus placebo in patients with ischemic cardiomyopathy and persistent chest pain or dyspnea despite optimal medical and revascularization therapy: randomized, double-blind crossover pilot study

    PubMed Central

    Shammas, Nicolas W; Shammas, Gail A; Keyes, Kathleen; Duske, Shawna; Kelly, Ryan; Jerin, Michael

    2015-01-01

    Background Patients with ischemic cardiomyopathy (ICM) may continue to experience persistent chest pain and/or dyspnea despite pharmacologic therapy and revascularization. We hypothesized that ranolazine would reduce anginal symptoms or dyspnea in optimally treated ICM patients. Methods In this randomized, double-blind, crossover-design pilot study, 28 patients with ICM (ejection fraction less or equal 40%) were included after providing informed consent. A total of 24 patients completed both placebo and ranolazine treatments and were analyzed. All patients were on treatment with a beta blocker, an angiotensin-converting enzyme inhibitor (or angiotensin receptor blocker), and at least one additional antianginal drug. After randomization, patients received up to 1,000 mg ranolazine orally twice a day, as tolerated, versus placebo. The primary end point was change in angina as assessed by the Seattle Angina Questionnaire (SAQ), or in dyspnea as assessed by the Rose Dyspnea Scale (RDS). Change in the RDS and SAQ score from baseline was compared, for ranolazine and placebo, using the Wilcoxon signed rank test or paired t-test. Results Patients had the following demographic and clinical variables: mean age of 71.5 years; male (82.1%); prior coronary bypass surgery (67.9%); prior coronary percutaneous intervention (85.7%); prior myocardial infarction (82.1%); diabetes (67.9%); and mean ejection fraction of 33.1%. No statistical difference was seen between baseline RDS score and that after placebo or ranolazine (n=20) (P≥0.05). There was however, an improvement in anginal frequency (8/10 patients) (P=0.058), quality of life (8/10 patients) (P=0.048), and mean score of all components of the SAQ questionnaire (n=10) (P=0.047) with ranolazine compared with placebo. Conclusion In optimally treated ICM patients with continued chest pain or dyspnea, ranolazine possibly had a positive impact on quality of life, a reduction in anginal frequency, and an overall improvement in the

  1. Adjuvant therapy with minocycline for schizophrenia (The MINOS Trial): study protocol for a double-blind randomized placebo-controlled trial

    PubMed Central

    2013-01-01

    Background Schizophrenia is understood to be a heterogeneous brain condition with overlapping symptom dimensions. The negative symptom dimension, with its protean cognitive manifestations, responds poorly to treatment, which can be a particular challenge in countries where clozapine therapy is not available. Preliminary data indicate that minocycline may be beneficial adjunct in the treatment of schizophrenia: positive, negative, and cognitive symptoms. In this study we aim to assess the efficacy of adjunctive minocycline to alleviate symptoms of schizophrenia in patients who have failed to respond to a therapeutic trial of antipsychotic medications. Methods The study is a parallel group, double-blind, randomized, placebo-controlled trial. Participants will be adults (aged 18 years and above) with first episode or relapse episode of schizophrenia of under 5 years’ duration. Patients who failed to show adequate therapeutic response to at least one antipsychotic medication given for a minimum of 4 weeks will be recruited from a psychiatry hospital in Addis Ababa and a psychiatry clinic in Butajira, Ethiopia. A total of 150 participants (75 in each arm) will be required to detect a five-point mean difference between the intervention arms adjusting for baseline symptom severity, at 90% power and 95% confidence. Patients in the intervention arm will receive minocycline (200 mg/day orally) added on to the regular antipsychotic medications participants are already on. Those in the placebo arm will receive an inactive compound identical in physical appearance to minocycline. Intervention will be offered for 12 weeks. Diagnosis will be established using the operational criteria for research (OPCRIT). Primary outcome measure will be a change in symptom severity measured using the positive and the negative syndrome scale for schizophrenia (PANSS). Secondary outcome measures will include changes in severity of negative symptoms, proportion achieving remission, and level

  2. Dual pathway therapy in acute coronary syndrome.

    PubMed

    Stachon, Peter; Ahrens, Ingo; Bode, Christoph; Zirlik, Andreas

    2016-08-01

    In 10 % of patients, who suffer an acute coronary syndrome (ACS), a major cardiovascular event occurs despite optimal therapy. The occlusion of the vessel is driven by atherothrombosis, which arises from platelet activation and activation of the coagulation cascade. In the last decade the secondary prevention continuously improved by development of dual anti-platelet therapy with new P2Y12-inhibitors such as clopidogrel, prasugrel, and ticagrelor. Until recently, the coagulation cascade was not targeted in secondary prevention. The coagulation factor Xa plays a crucial role in thrombosis and is elevated in patients after acute coronary syndrome, therefore representing an attractive target for novel therapies in ACS. Former studies with vitamin K antagonists showed reduction of cardiovascular events but increased major bleedings. Two phase-3 trials investigated the role of novel oral anticoagulant agents on top of aspirin and clopidogrel in patients with ACS. The APPRAISE-2 study, which tested the oral factor Xa inhibitor apixaban was prematurely terminated because of an increase of major bleedings in the absence of an effect on cardiovascular events. In contrast, the ATLAS ACS2 TIMI-51 trial interrogating the oral factor Xa inhibitor rivaroxaban in a low dose regimen showed significant reduction of cardiovascular events as well as total mortality. Thus, add-on treatment with low dose rivaroxaban emerged as a new option for patients with ACS. This review illustrates recent advances in the development of antithrombotic therapy in acute coronary syndromes, provides guidance on which patients should receive which therapy for secondary prevention of events, and points out potentially fruitful new strategies for the future of antithrombotic treatment in ACS. PMID:26660521

  3. Y2O3:Yb,Er@mSiO2-Cu(x)S double-shelled hollow spheres for enhanced chemo-/photothermal anti-cancer therapy and dual-modal imaging.

    PubMed

    Yang, Dan; Yang, Guixin; Wang, Xingmei; Lv, Ruichan; Gai, Shili; He, Fei; Gulzar, Arif; Yang, Piaoping

    2015-07-28

    Multifunctional composites have gained significant interest due to their unique properties which show potential in biological imaging and therapeutics. However, the design of an efficient combination of multiple diagnostic and therapeutic modes is still a challenge. In this contribution, Y2O3:Yb,Er@mSiO2 double-shelled hollow spheres (DSHSs) with up-conversion fluorescence have been successfully prepared through a facile integrated sacrifice template method, followed by a calcination process. It is found that the double-shelled structure with large specific surface area and uniform shape is composed of an inner shell of luminescent Y2O3:Yb,Er and an outer mesoporous silica shell. Ultra small Cu(x)S nanoparticles (about 2.5 nm) served as photothermal agents, and a chemotherapeutic agent (doxorubicin, DOX) was then attached onto the surface of mesoporous silica, forming a DOX-DSHS-Cu(x)S composite. The composite exhibits high anti-cancer efficacy due to the synergistic photothermal therapy (PTT) induced by the attached Cu(x)S nanoparticles and the enhanced chemotherapy promoted by the heat from the Cu(x)S-based PTT when irradiated by 980 nm near-infrared (NIR) light. Moreover, the composite shows excellent in vitro and in vivo X-ray computed tomography (CT) and up-conversion fluorescence (UCL) imaging properties owing to the doped rare earth ions, thus making it possible to achieve the target of imaging-guided synergistic therapy. PMID:26132588

  4. Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial

    PubMed Central

    2011-01-01

    Background Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux. Methods/design The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study. Discussion The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number ClinicalTrials (NCT): NCT01031667 PMID:21226953

  5. Cyclosporin A monotherapy versus cyclosporin A and methotrexate combination therapy in patients with early rheumatoid arthritis: a double blind randomised placebo controlled trial

    PubMed Central

    Gerards, A; Landewe, R; Prins, A; Bruijn, G; Goei, T; Laan, R; Dijkmans, B

    2003-01-01

    Patients and methods: 120 patients with active RA, rheumatoid factor positive and/or erosive, were randomly allocated to receive CsA with MTX (n=60) or CsA with placebo (n=60). Treatment with CsA was started in all patients at 2.5 mg/kg/day and increased to a maximum of 5 mg/kg/day in 16 weeks. MTX was started at 7.5 mg/week and increased to a maximal dose of 15 mg/week at week 16. Primary outcomes were clinical remission (Pinals criteria) and radiological damage (Larsen score), at week 48. Results: Treatment was discontinued prematurely in 27 patients in the monotherapy group (21 because of inefficacy, and six because of toxicity) and in 26 patients in the combination therapy group (14 and 12, respectively). At week 48, clinical remission was achieved in four patients in the monotherapy group and in six patients in the combination therapy group (p=0.5). The median Larsen score increased to 10 (25th, 75th centiles: 3.5; 13.3) points in the monotherapy group and to 4 (1.0; 10.5) points in the combination therapy group (p=0.004). 28/60 (47%) of patients in the monotherapy group v 34/60 (57%) of patients in the combination therapy group had reached an American college of Rheumatology 20% (ACR20) response (p=0.36) at week 48; 15/60 (25%) v 29/60 (48%) of patients had reached an ACR50 response (p=0.013); and 7 (12%) v 12 (20%) of patients had reached an ACR70 response (p=0.11).Their was a tendency towards more toxicity in the combination therapy group. Conclusions: In patients with early RA, neither CsA plus MTX combination therapy nor CsA monotherapy is very effective in inducing clinical remission. Combination therapy is probably better at improving clinical disease activity, and definitely better at slowing radiological progression. Combination therapy should still be compared with methotrexate monotherapy. PMID:12634224

  6. Efficacy of high and low level laser therapy in the treatment of Bell's palsy: a randomized double blind placebo-controlled trial.

    PubMed

    Alayat, Mohamed Salaheldien Mohamed; Elsodany, Ahmed Mohamed; El Fiky, Amir Abdel Raouf

    2014-01-01

    The aim of the present study was to investigate and compare the effects of high intensity laser therapy (HILT) and low level laser therapy (LLLT) on the treatment of patients with Bell's palsy. Forty-eight patients participated in and completed this study. The mean age was 43 ± 9.8 years. They were randomly assigned into three groups: HILT group, LLLT group, and exercise group. All patients were treated with facial massage and exercises, but the HILT and LLLT groups received the respective laser therapy. The grade of facial recovery was assessed by the facial disability scale (FDI) and the House-Brackmann scale (HBS). Evaluation was carried out 3 and 6 weeks after treatment for all patients. Laser treatments included eight points on the affected side of the face three times a week for 6 successive weeks. FDI and HBS were used to assess the grade of recovery. The scores of both FDI and HBS were taken before as well as 3 and 6 weeks after treatment. The Friedman test and Wilcoxon signed ranks test were used to compare the FDI and HBS scores within each group. The result showed that both HILT and LLLT significantly improved the recovery of patients with Bell's palsy. Moreover, HILT was the most effective treatment modality compared to LLLT and massage with exercises. Thus, both HILT and LLLT are effective physical therapy modalities for the recovery of patients with Bell's palsy, with HILT showing a slightly greater improvement than LLLT. PMID:23709010

  7. Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial.

    PubMed

    Abdelkefi, Abderrahman; Ladeb, Saloua; Torjman, Lamia; Othman, Tarek Ben; Lakhal, Amel; Romdhane, Neila Ben; Omri, Halima El; Elloumi, Moez; Belaaj, Hatem; Jeddi, Ramzi; Aissaouï, Lamia; Ksouri, Habib; Hassen, Assia Ben; Msadek, Fahmi; Saad, Ali; Hsaïri, Mohamed; Boukef, Kamel; Amouri, Ahlem; Louzir, Hechmi; Dellagi, Koussay; Abdeladhim, Abdeladhim Ben

    2008-02-15

    From April 2003 to December 2006, 195 patients with de novo symptomatic myeloma and younger than 60 years of age were randomly assigned to receive either tandem transplantation up front (arm A, n = 97) or one autologous stem-cell transplantation followed by a maintenance therapy with thalidomide (day + 90, 100 mg per day during 6 months) (arm B, n = 98). Patients included in arm B received a second transplant at disease progression. In both arms, autologous stem-cell transplantation was preceded by first-line therapy with thalidomide-dexamethasone and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide (4 g/m(2)) and granulocyte colony stimulating factor. Data were analyzed on an intent-to-treat basis. With a median follow-up of 33 months (range, 6-46 months), the 3-year overall survival was 65% in arm A and 85% in arm B (P = .04). The 3-year progression-free survival was 57% in arm A and 85% in arm B (P = .02). Up-front single autologous transplantation followed by 6 months of maintenance therapy with thalidomide (with second transplant in reserve for relapse or progression) is an effective therapeutic strategy to treat multiple myeloma patients and appears superior to tandem transplant in this setting. This study was registered at www.ClinicalTrials.gov as (NCT 00207805). PMID:17875806

  8. Adjuvant antifungal therapy using tissue tolerable plasma on oral mucosa and removable dentures in oral candidiasis patients: a randomised double-blinded split-mouth pilot study.

    PubMed

    Preissner, Saskia; Kastner, Isabell; Schütte, Eyke; Hartwig, Stefan; Schmidt-Westhausen, Andrea Maria; Paris, Sebastian; Preissner, Robert; Hertel, Moritz

    2016-07-01

    Extended use of antimycotics in oral candidiasis therapy gives rise to problems related to fungal drug resistance. The aim of this pilot study was to investigate the efficacy of tissue tolerable plasma (TTP) in denture stomatitis patients. It was hypothesised that (I): erythema and (IIa): complaint remission would be accelerated and (IIb): colony forming unit (CFU) reduction would be improved. The halves of the upper jaws of eight patients were randomly assigned to control (nystatin, chlorhexidine and placebo treatment) and test sides (nystatin, chlorhexidine and TTP administered six times each 7 days). The patients and the investigators, who were different from the therapists, were both blinded. Compared to the control sides, the erythema surface was reduced significantly more extensively on the test sides between 2 and 6 weeks of antifungal therapy (P ≤ 0.05). Visual analogue scale values and the frequency of moderate or heavy growth of Candida post-treatment did not differ significantly between both sides (P > 0.05). The primary hypothesis was confirmed, which may be interpreted as an accelerated remission. As drug therapy is usually limited to the time in which signs of infection are present, TTP might help reducing antifungal use. Even though the secondary hypotheses were not confirmed, persistence of Candida might be only colonisation. PMID:26932256

  9. Efficacy of nifedipine therapy in patients with sphincter of Oddi dysfunction: a prospective, double-blind, randomized, placebo-controlled, cross over trial.

    PubMed Central

    Khuroo, M S; Zargar, S A; Yattoo, G N

    1992-01-01

    1. Twenty-eight patients who fulfilled entry criteria for sphincter of Oddi dysfunction were randomly allocated to receive nifedipine and placebo in a cross over design with 12 week treatment periods separated by a 2 week wash-out. 2. All patients had episodic pain resembling biliary pain, had previously undergone cholecystectomy, had elevated alkaline phosphatase during episodes of pain and had elevated basal pressure on sphincter of Oddi manometry. 3. Compared with placebo, significant decreases in cumulative pain score, number of pain episodes, oral analgesic tablets consumed and emergency room visits were observed during nifedipine treatment. 4. Overall 21 patients improved during nifedipine therapy while seven patients did not. None of the following predicted response to nifedipine therapy: enzyme levels, morphine-Prostigmine test, fatty meal sonography, common duct diameter and pressure, sphincter of Oddi phasic pressure, frequency and duration of phasic waves and maximal fall in the basal pressure at sphincter of Oddi manometry after sublingual administration of nifedipine. However patients with predominant antegrade propagation of phasic contractions of sphincter of Oddi did significantly better on nifedipine than those with abnormal propagation of phasic contractions. 5. Nifedipine therapy orally in maximal tolerated doses relieves pain in patients with sphincter of Oddi dysfunction who have elevated basal pressure and sphincter of Oddi phasic contractions of predominantly antegrade nature. PMID:1524959

  10. Efficacy of high-intensity laser therapy in the treatment of chronic neck pain: a randomized double-blind placebo-control trial.

    PubMed

    Alayat, Mohamed Salaheldien Mohamed; Mohamed, Ashraf Abdelaal; Helal, Omar Farouk; Khaled, Osama Ahmed

    2016-05-01

    The aim of the study was to investigate the effect of high-intensity laser therapy (HILT) in treatment of patients with chronic neck pain (CNP) on cervical range of motion (ROM), pain, and functional activity. Sixty male patients participated in this study with mean (SD) age of 35.47 (4.18) years. Patients were randomly assigned into two groups and treated with HILT plus exercise (HILT + EX) and placebo laser plus exercise (PL + EX) in groups 1 and 2, respectively. The outcomes measured were cervical ROM, pain level by visual analog scale (VAS), and functional activity by neck disability index (NDI) score. Statistical analyses were performed to compare the differences between baseline and post-treatment. The level of statistical significance was set as p < 0.05. Cervical ROM significantly increased after 6 weeks of treatment in all groups. VAS and NDI results showed significant decrease post-treatment in both groups. HILT + EX effectively increased cervical ROM and decreased VAS and NDI scores after 6 weeks of treatment compared to PL + EX. HILT + EX is an effective physical therapy modality for patients with CNP compared to PL + EX therapy. The combination of HILT + EX effectively increased cervical ROM, functional activity, and reduced pain after 6 weeks of treatment. PMID:26914684

  11. Efficacy of the long-acting nitro vasodilator pentaerithrityl tetranitrate in patients with chronic stable angina pectoris receiving anti-anginal background therapy with beta-blockers: a 12-week, randomized, double-blind, placebo-controlled trial

    PubMed Central

    Münzel, Thomas; Meinertz, Thomas; Tebbe, Ulrich; Schneider, Heinrich Theodor; Stalleicken, Dirk; Wargenau, Manfred; Gori, Tommaso; Klingmann, Ingrid

    2014-01-01

    Background The organic nitrate pentaerithrityl tetranitrate (PETN) has been shown to have ancillary properties that prevent the development of tolerance and endothelial dysfunction. This randomized, double-blind, placebo-controlled, multicentre study (‘CLEOPATRA’ study) was designed to investigate the anti-ischaemic efficacy of PETN 80 mg b.i.d. (morning and mid-day) over placebo in patients with chronic stable angina pectoris. Methods and results A total of 655 patients were evaluated in the intention-to-treat population, randomized to PETN (80 mg b.i.d., n = 328) or placebo (n = 327) and completed the study. Patients underwent treadmill exercise tests at randomization, after 6 and 12 weeks of treatment. Treatment with PETN over 12 weeks did not modify the primary endpoint total exercise duration (TED, P = 0.423). In a pre-specified sub-analysis of patients with reduced exercise capacity (TED at baseline ≤9 min, n = 257), PETN appeared more effective than placebo treatment (P = 0.054). Superiority of PETN over placebo was evident in patients who were symptomatic at low exercise levels (n = 120; P = 0.017). Pentaerithrityl tetranitrate 80 mg b.i.d. was well tolerated, and the overall safety profile was comparable with placebo. Conclusion Although providing no additional benefit in unselected patients with known coronary artery disease, PETN therapy, administered in addition to modern anti-ischaemic therapy, could increase exercise tolerance in symptomatic patients with reduced exercise capacity. PMID:24071762

  12. Muscular pre-conditioning using light-emitting diode therapy (LEDT) for high-intensity exercise: a randomized double-blind placebo-controlled trial with a single elite runner

    PubMed Central

    Ferraresi, Cleber; Beltrame, Thomas; Fabrizzi, Fernando; do Nascimento, Eduardo Sanches Pereira; Karsten, Marlus; de Oliveira Francisco, Cristina; Borghi-Silva, Audrey; Catai, Aparecida Maria; Cardoso, Daniel Rodrigues; Ferreira, Antonio Gilberto; Hamblin, Michael R.; Bagnato, Vanderlei Salvador; Parizotto, Nivaldo Antonio

    2015-01-01

    Recently, low-level laser (light) therapy (LLLT) has been used to improve muscle performance. This study aimed to evaluate the effectiveness of near-infrared light-emitting diode therapy (LEDT) and its mechanisms of action to improve muscle performance in an elite athlete. The kinetics of oxygen uptake (VO2), blood and urine markers of muscle damage (creatine kinase – CK and alanine) and fatigue (lactate) were analyzed. Additionally, some metabolic parameters were assessed in urine using proton nuclear magnetic resonance spectroscopy (1H NMR). A LED cluster with 50 LEDs (λ = 850 nm; 50mW 15 s; 37.5 J) was applied on legs, arms and trunk muscles of a single runner athlete 5 min before a high-intense constant workload running exercise on treadmill. The athlete received either Placebo-1-LEDT; Placebo-2-LEDT; or Effective-LEDT in a randomized double-blind placebo-controlled trial with washout period of 7 d between each test. LEDT improved the speed of the muscular VO2 adaptation (~−9 s), decreased O2 deficit (~−10 L), increased the VO2 from the slow component phase (~+348 ml min−1) and increased the time limit of exercise (~+589 s). LEDT decreased blood and urine markers of muscle damage and fatigue (CK, alanine and lactate levels). The results suggest that a muscular pre-conditioning regimen using LEDT before intense exercises could modulate metabolic and renal function to achieve better performance. PMID:25585514

  13. Association between Genetic Variants in DNA Double-Strand Break Repair Pathways and Risk of Radiation Therapy-Induced Pneumonitis and Esophagitis in Non-Small Cell Lung Cancer

    PubMed Central

    Zhao, Lina; Pu, Xia; Ye, Yuanqing; Lu, Charles; Chang, Joe Y.; Wu, Xifeng

    2016-01-01

    Radiation therapy (RT)-induced pneumonitis and esophagitis are commonly developed side effects in non-small cell lung cancer (NSCLC) patients treated with definitive RT. Identifying patients who are at increased risk for these toxicities would help to maximize treatment efficacy while minimizing toxicities. Here, we systematically investigated single nucleotide polymorphisms (SNPs) within double-strand break (DSB) repair pathway as potential predictive markers for radiation-induced esophagitis and pneumonitis. We genotyped 440 SNPs from 45 genes in DSB repair pathways in 250 stage I–III NSCLC patients who received definitive radiation or chemoradiation therapy, followed by internal validation in 170 additional patients. We found that 11 SNPs for esophagitis and 8 SNPs for pneumonitis showed consistent effects between discovery and validation populations (same direction of OR and reached significance in meta-analysis). Among them, rs7165790 in the BLM gene was significantly associated with decreased risk of esophagitis in both discovery (OR = 0.59, 95% CI: 0.37–0.97, p = 0.037) and validation subgroups (OR = 0.45, 95% CI: 0.22–0.94, p = 0.032). A strong cumulative effect was observed for the top SNPs, and gene-based tests revealed 12 genes significantly associated with esophagitis or pneumonitis. Our results support the notion that genetic variations within DSB repair pathway could influence the risk of developing toxicities following definitive RT in NSCLC. PMID:26901225

  14. A Phase III, Double-Blind, Placebo-Controlled Prospective Randomized Clinical Trial of d-Threo-Methylphenidate HCl in Brain Tumor Patients Receiving Radiation Therapy

    SciTech Connect

    Butler, Jerome M. Case, L. Douglas; Atkins, James; Frizzell, Bart; Sanders, George; Griffin, Patricia; Lesser, Glenn; McMullen, Kevin; McQuellon, Richard; Naughton, Michelle; Rapp, Stephen; Stieber, Volker; Shaw, Edward G.

    2007-12-01

    Purpose: The quality of life (QOL) and neurocognitive function of patients with brain tumors are negatively affected by the symptoms of their disease and brain radiation therapy (RT). We assessed the effect of prophylactic d-threo-methylphenidate HCl (d-MPH), a central nervous system (CNS) stimulant on QOL and cognitive function in patients undergoing RT. Methods and Materials: Sixty-eight patients with primary or metastatic brain tumors were randomly assigned to receive d-MPH or placebo. The starting dose of d-MPH was 5 mg twice daily (b.i.d.) and was escalated by 5 mg b.i.d. to a maximum of 15 mg b.i.d. The placebo was administered as one pill b.i.d. escalating three pills b.i.d. The primary outcome was fatigue. Patients were assessed at baseline, the end of radiation therapy, and 4, 8, and 12 weeks after brain RT using the Functional Assessment of Cancer Therapy with brain and fatigue (FACIT-F) subscales, as well as the Center for Epidemiologic Studies Scale and Mini-Mental Status Exam. Results: The Mean Fatigue Subscale Score at baseline was 34.7 for the d-MPH arm and 33.3 for the placebo arm (p = 0.61). At 8 weeks after the completion of brain RT, there was no difference in fatigue between patient groups. The adjusted least squares estimate of the Mean Fatigue Subscale Score was 33.7 for the d-MPH and 35.6 for the placebo arm (p = 0.64). Secondary outcomes were not different between the two treatment arms. Conclusions: Prophylactic use of d-MPH in brain tumor patients undergoing RT did not result in an improvement in QOL.

  15. A Local CC2 and TDA-DFT Double Hybrid Study on BODIPY/aza-BODIPY Dimers as Heavy Atom Free Triplet Photosensitizers for Photodynamic Therapy Applications.

    PubMed

    Momeni, Mohammad R; Brown, Alex

    2016-04-28

    A series of 11 different boron-dipyrromethene (BODIPY) dimers is carefully examined by means of ab initio and Tamm-Dancoff approximated density functional theory methods. Vertical and 0-0 excitation energies along with the tetraradical character of these dimers are determined. Possible application of a series of linked dimers for photodynamic therapy (PDT) was investigated through computing their excitation energies, spin-orbit coupling matrix elements, and singlet-triplet energy gaps. Finally through a systematic investigation of a series of 36 different BODIPY and aza-BODIPY dimers, a new class of near-IR heavy atom free photosensitizers for PDT action is introduced. PMID:27035753

  16. Comparative Efficacy and Durability of Continuation Phase Cognitive Therapy for Preventing Recurrent Depression: Design of a Double-Blinded, Fluoxetine- and Pill-Placebo–Controlled, Randomized Trial with 2-Year Follow-up

    PubMed Central

    Thase, Michael E.

    2010-01-01

    Background Major depressive disorder (MDD) is highly prevalent and associated with disability and chronicity. Although cognitive therapy (CT) is an effective short-term treatment for MDD, a significant proportion of responders subsequently suffer relapses or recurrences. Purpose This design prospectively evaluates: 1) a method to discriminate CT-treated responders at lower versus higher risk for relapse; and 2) the subsequent durability of 8-month continuation phase therapies in randomized higher risk responders followed for an additional 24-months. The primary prediction is: after protocol treatments are stopped, higher risk patients randomly assigned to continuation phase CT (C-CT) will have a lower risk of relapse/recurrence than those randomized to fluoxetine (FLX). Methods Outpatients, aged 18 to 70 years, with recurrent MDD received 12–14 weeks of CT provided by 15 experienced therapists from two sites. Responders (i.e., no MDD and 17-item Hamilton Rating Scale for Depression ≤ 12) were stratified into higher and lower risk groups based on stability of remission during the last 6 weeks of CT. The lower risk group entered follow-up for 32 months; the higher risk group was randomized to 8 months of continuation phase therapy with either C-CT or clinical management plus either double-blinded FLX or pill placebo. Following the continuation phase, higher risk patients were followed by blinded evaluators for 24 months. Results The trial began in 2000. Enrollment is complete (N=523). The follow-up continues. Conclusions The trial evaluates the preventive effects and durability of acute and continuation phase treatments in the largest known sample of CT responders collected worldwide. PMID:20451668

  17. Effects of dabigatran on the cellular and protein phase of coagulation in patients with coronary artery disease on dual antiplatelet therapy with aspirin and clopidogrel. Results from a prospective, randomised, double-blind, placebo-controlled study.

    PubMed

    Franchi, Francesco; Rollini, Fabiana; Cho, Jung Rae; King, Rhodri; Phoenix, Fladia; Bhatti, Mona; DeGroat, Christopher; Tello-Montoliu, Antonio; Zenni, Martin M; Guzman, Luis A; Bass, Theodore A; Ajjan, Ramzi A; Angiolillo, Dominick J

    2016-03-01

    There is growing interest in understanding the effects of adding an oral anticoagulant in patients on dual antiplatelet therapy (DAPT). Vitamin K antagonists (VKAs) and clopidogrel represent the most broadly utilised oral anticoagulant and P2Y12 receptor inhibitor, respectively. However, VKAs can interfere with clopidogrel metabolism via the cytochrome P450 (CYP) system which in turn may result in an increase in platelet reactivity. Dabigatran is a direct acting (anti-II) oral anticoagulant which does not interfere with CYP and has favourable safety and efficacy profiles compared with VKAs. The pharmacodynamic (PD) effects on platelet reactivity and clot kinetic of adjunctive dabigatran therapy in patients on DAPT are poorly explored. In this prospective, randomised, double-blind, placebo-controlled PD study, patients (n=30) on maintenance DAPT with aspirin and clopidogrel were randomised to either dabigatran 150 mg bid or placebo for seven days. PD testing was performed before and after treatment using four different assays exploring multiple pathways of platelet aggregation and fibrin clot kinetics: light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA), kaolin-activated thromboelastography (TEG) and turbidimetric assays. There were no differences in multiple measures of platelet reactivity investigating purinergic and non-purinergic signaling pathways assessed by LTA, MEA and TEG platelet mapping. Dabigatran significantly increased parameters related to thrombin activity and thrombus generation, and delayed fibrin clot formation, without affecting clot structure or fibrinolysis. In conclusion, in patients on DAPT with aspirin and clopidogrel, adjunctive dabigatran therapy is not associated with modulation of profiles of platelet reactivity as determined by several assays assessing multiple platelet signalling pathways. However, dabigatran significantly interferes with parameters related to thrombin activity and delays fibrin clot formation

  18. Iron Oxide Decorated MoS2 Nanosheets with Double PEGylation for Chelator-Free Radiolabeling and Multimodal Imaging Guided Photothermal Therapy

    PubMed Central

    Liu, Teng; Shi, Sixiang; Liang, Chao; Shen, Sida; Cheng, Liang; Wang, Chao; Song, Xuejiao; Goel, Shreya; Barnhart, Todd E.; Cai, Weibo; Liu, Zhuang

    2015-01-01

    Theranostics for in vivo cancer diagnosis and treatment generally requires well-designed nanoscale platforms with multiple integrated functionalities. In this study, we uncover that functionalized iron oxide nanoparticles (IONPs) could be self-assembled on the surface of two-dimensional MoS2 nanosheets via sulfur chemistry, forming MoS2-IO nanocomposites, which are then modified with two types of polyethylene glycol (PEG) to acquire enhanced stability in physiological environments. Interestingly, 64Cu, a commonly used positron-emitting radioisotope, could be firmly adsorbed on the surface of MoS2 without the need of chelating molecules, to enable in vivo positron emission tomography (PET) imaging. On the other hand, the strong near-infrared (NIR) and superparamagnetism of MoS2-IO-PEG could also be utilized for photoacoustic tomography (PAT) and magnetic resonance (MR) imaging, respectively. Under the guidance by such triple-modal imaging, which uncovers efficient tumor retention of MoS2-IO-(d)PEG upon intravenous injection, in vivo photothermal therapy is finally conducted, achieving effective tumor ablation in an animal tumor model. Our study highlights the promise of constructing multifunctional theranostic nanocomposites based on 2D transitional metal dichalcogenides for multimodal imaging-guided cancer therapy. PMID:25562533

  19. Protocol for the Smoking, Nicotine and Pregnancy (SNAP) trial: double-blind, placebo-randomised, controlled trial of nicotine replacement therapy in pregnancy

    PubMed Central

    Coleman, Tim; Thornton, Jim; Britton, John; Lewis, Sarah; Watts, Kim; Coughtrie, Michael WH; Mannion, Clare; Marlow, Neil; Godfrey, Christine

    2007-01-01

    Background Smoking in pregnancy remains a public health challenge. Nicotine replacement therapy (NRT) is effective for smoking cessation in non-pregnant people, but because women metabolise nicotine and cotinine much faster in pregnancy, it is unclear whether this will be effective for smoking cessation in pregnancy. The NHS Health Technology Assessment Programme (HTA)-funded smoking, nicotine and pregnancy (SNAP) trial will investigate whether or not nicotine replacement therapy (NRT) is effective, cost-effective and safe when used for smoking cessation by pregnant women. Methods/Design Over two years, in 5 trial centres, 1050 pregnant women who are between 12 and 24 weeks pregnant will be randomised as they attend hospital for ante-natal ultrasound scans. Women will receive either nicotine or placebo transdermal patches with behavioural support. The primary outcome measure is biochemically-validated, self-reported, prolonged and total abstinence from smoking between a quit date (defined before randomisation and set within two weeks of this) and delivery. At six months after childbirth self-reported maternal smoking status will be ascertained and two years after childbirth, self-reported maternal smoking status and the behaviour, cognitive development and respiratory symptoms of children born in the trial will be compared in both groups. Discussion This trial is designed to ascertain whether or not standard doses of NRT (as transdermal patches) are effective and safe when used for smoking cessation during pregnancy. PMID:17201904

  20. Iron oxide decorated MoS2 nanosheets with double PEGylation for chelator-free radiolabeling and multimodal imaging guided photothermal therapy.

    PubMed

    Liu, Teng; Shi, Sixiang; Liang, Chao; Shen, Sida; Cheng, Liang; Wang, Chao; Song, Xuejiao; Goel, Shreya; Barnhart, Todd E; Cai, Weibo; Liu, Zhuang

    2015-01-27

    Theranostics for in vivo cancer diagnosis and treatment generally requires well-designed nanoscale platforms with multiple integrated functionalities. In this study, we uncover that functionalized iron oxide nanoparticles (IONPs) could be self-assembled on the surface of two-dimensional MoS2 nanosheets via sulfur chemistry, forming MoS2-IO nanocomposites, which are then modified with two types of polyethylene glycol (PEG) to acquire enhanced stability in physiological environments. Interestingly, (64)Cu, a commonly used positron-emitting radioisotope, could be firmly adsorbed on the surface of MoS2 without the need of chelating molecules, to enable in vivo positron emission tomography (PET) imaging. On the other hand, the strong near-infrared (NIR) and superparamagnetism of MoS2-IO-PEG could also be utilized for photoacoustic tomography (PAT) and magnetic resonance (MR) imaging, respectively. Under the guidance by such triple-modal imaging, which uncovers efficient tumor retention of MoS2-IO-(d)PEG upon intravenous injection, in vivo photothermal therapy is finally conducted, achieving effective tumor ablation in an animal tumor model. Our study highlights the promise of constructing multifunctional theranostic nanocomposites based on 2D transitional metal dichalcogenides for multimodal imaging-guided cancer therapy. PMID:25562533

  1. Effectiveness of ultrasound treatment applied with exercise therapy on patients with ankylosing spondylitis: a double-blind, randomized, placebo-controlled trial.

    PubMed

    Şilte Karamanlioğlu, Duygu; Aktas, Ilknur; Ozkan, Feyza Unlu; Kaysin, Meryem; Girgin, Nuray

    2016-05-01

    The aim of our study was to evaluate effectiveness of ultrasound treatment applied with exercise therapy in patients with ankylosing spondylitis. Fifty-two patients, who were diagnosed according to modified New York criteria, were aged 25-60, and have spine pain, were randomly assigned to two groups. Ultrasound (US) and exercise therapy were applied to treatment group (27); placebo US treatment and exercise therapy were applied to control group (25). Patients were evaluated before treatment, at the end of treatment, and 4 weeks after the treatment. Daily and night pain, morning stiffness, patient global assessment (PGA), doctor global assessment (DGA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire, Ankylosing Spondylitis Disease Activity Score (ASDAS) erythrocyte sedimentation rate (ESR), and ASDAS C-reactive protein (CRP) were used as clinical parameters. In US group, all parameters showed significant improvements at 2 and 6 weeks, in comparison with the baseline. In placebo US group, significant improvement was obtained for all parameters (except tragus-to-wall distance and modified Schober test at 2 weeks and lumbar side flexion and modified Schober test at 6 weeks). Comparison of the groups showed significantly superior results of US group for parameters of BASMI (p < 0.05), tragus-wall distance (p < 0.05), PGA (p < 0.01), and DGA (p < 0.05) at 2 weeks as well as for the parameters of daily pain (p < 0.01), PGA (p < 0.05), DGA (p < 0.01), BASDAI (p < 0.05), ASDAS-CRP (p < 0.05), ASDAS-ESR (p < 0.01), lumbar side flexion (p < 0.01), the modified Schober test (p < 0.01), and ASQoL (p < 0.05) at 6 weeks. Our study showed that ultrasound treatment increases the effect of exercise in patients with ankylosing spondylitis. PMID:26923690

  2. Analgesic Effects of Intra-Articular Bupivacaine/Intravenous Parecoxib Combination Therapy versus Intravenous Parecoxib Monotherapy in Patients Receiving Total Knee Arthroplasty: A Randomized, Double-Blind Trial

    PubMed Central

    Shen, Shih-Jyun; Peng, Pei-Yu; Chen, Hsiu-Pin; Lin, Jr-Rung; Lee, Mel S.; Yu, Huang-Ping

    2015-01-01

    Objectives. The purpose of this double-blind, randomized study was to investigate whether the addition of intra-articular bupivacaine to intravenous parecoxib could improve pain relief in patients undergoing total knee arthroplasty. Methods. A total of 36 patients undergoing total knee arthroplasty were enrolled into our study. These patients were randomly allocated either to a placebo-controlled group or study group. Postoperative pain scores and analgesic consumption were evaluated. Results. Numeric rating scale (NRS) data of bupivacaine group in postoperative room were significantly lower than that of control group (control group versus bupivacaine group, 7.9 (6.7–9.1) (mean and 95% confidence interval) versus 4.5 (3.2–5.8) (mean and 95% confidence interval), p = 0.001). NRS data of bupivacaine group in ward were also significantly lower than that of control group. A significantly lower dose of meperidine was used in the study group postoperatively during the first 24 hours (control group versus bupivacaine group, 3.08 ± 0.80 mg/Kg versus 2.34 ± 0.42 mg/Kg, p = 0.001). Conclusion. Intra-articular bupivacaine in combination with intravenous parecoxib may improve pain relief and reduce the demand for rescue analgesics in patients undergoing total knee arthroplasty. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12615000463572). PMID:26171392

  3. Duration of Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Patients With and Without Acute Coronary Syndrome: A Systematic Review of Randomized Controlled Trials.

    PubMed

    Sharma, Abhishek; Lavie, Carl J; Sharma, Samin K; Garg, Akash; Vallakati, Ajay; Mukherjee, Debabrata; Marmur, Jonathan D

    2016-08-01

    In this systemic review we evaluated the efficacy and safety of long duration dual anti-platelet therapy (DAPT) (L-DAPT) compared with short duration DAPT (S-DAPT) after drug-eluting stent (DES) implantation in patients who presented with or without acute coronary syndromes (ACS). We identified 8 randomized controlled trials in which 30,975 patients were randomized to S-DAPT versus L-DAPT (12,421 ACS and 18,554 non-ACS). Short duration dual anti-platelet therapy was associated with an increase in target vessel revascularization (TVR) in ACS patients, but the difference was not significant for non-ACS patients (odds ratio [OR] 5.04 [95% CI, 1.28-19.76], and OR, 0.89 [95% CI, 0.51-1.55], respectively). The risk of cardiac mortality was not significantly different with S-DAPT and L-DAPT for ACS (OR, 1.69 [95% CI, 0.82-3.50]) and non-ACS patients (OR, 0.89 [95% CI, 0.57-1.37]). For all cause mortality, myocardial infarction, and stent thrombosis, most of the events were derived from the DAPT study, thus a meta-analysis was not performed for these end points. Based on our review of the literature, we conclude that S-DAPT was associated with higher rates of stent thrombosis and myocardial infarction, and non-significant differences in all-cause mortality, with no significant interactions according to ACS vs non-ACS. However, in non-ACS patients, the benefit-risk profile favored S-DAPT, with lower all-cause mortality, whereas the trends were reversed in ACS. Additional studies are required to determine if the benefit-risk profile of S-DAPT vs L-DAPT varies according to clinical syndrome. PMID:27492914

  4. Efficacy and tolerability of adding coenzyme A 400 U/d capsule to stable statin therapy for the treatment of patients with mixed dyslipidemia: an 8-week, multicenter, double-Blind, randomized, placebo-controlled study

    PubMed Central

    2014-01-01

    Background Patients with mixed hyperlipidemia usually are in need of combination therapy to achieve low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) target values for reduction of cardiovascular risk. This study investigated the efficacy and safety of adding a new hypolipidemic agent, coenzyme A (CoA) to stable statin therapy in patients with mixed hyperlipidemia. Methods In this multi-center, 8-week, double-blind study, adults who had received ≥8 weeks of stable statin therapy and had hypertriglyceridemia (TG level at 2.3-6.5 mmol/L) were randomized to receive CoA 400 U/d or placebo plus stable dosage of statin. Efficacy was assessed by the changes in the levels and patterns of lipoproteins. Tolerability was assessed by the incidence and severity of adverse events (AEs). Results A total of 304 patients with mixed hyperlipidemia were randomized to receive CoA 400 U/d plus statin or placebo plus statin (n = 152, each group). After treatment for 8 weeks, the mean percent change in TG was significantly greater with CoA plus statin compared with placebo plus statin (-25.9% vs -4.9%, respectively; p = 0.0003). CoA plus statin was associated with significant reductions in TC (-9.1% vs -3.1%; p = 0.0033), LDL-C (-9.9% vs 0.1%; p = 0.003), and non- high-density lipoprotein cholesterol (-13.5% vs -5.7%; p = 0.0039). There was no significant difference in the frequency of AEs between groups. No serious AEs were considered treatment related. Conclusions In these adult patients with persistent hypertriglyceridemia, CoA plus statin therapy improved TG and other lipoprotein parameters to a greater extent than statin alone and has no obviously adverse effect. Trial registration Current Controlled Trials ClinicalTrials.gov ID NCT01928342. PMID:24382338

  5. Double Layers in Astrophysics

    NASA Technical Reports Server (NTRS)

    Williams, Alton C. (Editor); Moorehead, Tauna W. (Editor)

    1987-01-01

    Topics addressed include: laboratory double layers; ion-acoustic double layers; pumping potential wells; ion phase-space vortices; weak double layers; electric fields and double layers in plasmas; auroral double layers; double layer formation in a plasma; beamed emission from gamma-ray burst source; double layers and extragalactic jets; and electric potential between plasma sheet clouds.

  6. Double screening

    NASA Astrophysics Data System (ADS)

    Gratia, Pierre; Hu, Wayne; Joyce, Austin; Ribeiro, Raquel H.

    2016-06-01

    Attempts to modify gravity in the infrared typically require a screening mechanism to ensure consistency with local tests of gravity. These screening mechanisms fit into three broad classes; we investigate theories which are capable of exhibiting more than one type of screening. Specifically, we focus on a simple model which exhibits both Vainshtein and kinetic screening. We point out that due to the two characteristic length scales in the problem, the type of screening that dominates depends on the mass of the sourcing object, allowing for different phenomenology at different scales. We consider embedding this double screening phenomenology in a broader cosmological scenario and show that the simplest examples that exhibit double screening are radiatively stable.

  7. Effect of Ruxolitinib Therapy on Myelofibrosis-Related Symptoms and Other Patient-Reported Outcomes in COMFORT-I: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Mesa, Ruben A.; Gotlib, Jason; Gupta, Vikas; Catalano, John V.; Deininger, Michael W.; Shields, Alan L.; Miller, Carole B.; Silver, Richard T.; Talpaz, Moshe; Winton, Elliott F.; Harvey, Jimmie H.; Hare, Thomas; Erickson-Viitanen, Susan; Sun, William; Sandor, Victor; Levy, Richard S.; Kantarjian, Hagop M.; Verstovsek, Srdan

    2013-01-01

    Purpose To assess the effects of ruxolitinib on symptom burden and quality of life (QoL) and to evaluate the ability of the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 to measure meaningful changes in myelofibrosis-related symptoms in patients with myelofibrosis. Patients and Methods COMFORT-I (Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment–I) is a double-blind, placebo-controlled phase III study evaluating ruxolitinib in patients with intermediate-2 or high-risk myelofibrosis. Exploratory analyses were conducted on the following patient-reported outcomes (PROs) assessments: modified MFSAF v2.0 (individual symptoms and Total Symptom Score [TSS]), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale, and Patient Global Impression of Change (PGIC). Results Patients receiving ruxolitinib experienced improvements in individual myelofibrosis-related symptoms, although patients receiving placebo experienced worsening (P < .001). The majority (91%) of ruxolitinib-treated patients designated as ≥ 50% TSS responders (≥ 50% TSS improvement) self-reported their condition as either “Much improved” or “Very much improved” on the PGIC. These patients achieved significant improvements in the EORTC QLQ-C30 functional domains and Global Health Status/QoL versus patients receiving placebo, who experienced worsening on these measures (P ≤ .0135). Ruxolitinib-treated patients with a lesser degree of symptom improvement (< 50% TSS responders) also achieved improvements over placebo on these measures. The degree of spleen volume reduction with ruxolitinib correlated with improvements in TSS, PGIC, PROMIS Fatigue Scale, and EORTC Global Health Status/QoL. Ruxolitinib-treated patients who achieved a ≥ 35% reduction in spleen volume experienced the greatest improvements in these PROs. Conclusion

  8. Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial

    PubMed Central

    Sperling, Michael R; Abou-Khalil, Bassel; Harvey, Jay; Rogin, Joanne B; Biraben, Arnaud; Galimberti, Carlo A; Kowacs, Pedro A; Hong, Seung Bong; Cheng, Hailong; Blum, David; Nunes, Teresa; Soares-da-Silva, Patrício

    2015-01-01

    Objective To evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial-onset seizures. Methods This randomized, placebo-controlled, double-blind, parallel-group, phase III study was conducted at 173 centers in 19 countries, including the United States and Canada. Eligible patients were aged ≥16 years and had uncontrolled partial-onset seizures despite treatment with 1–2 antiepileptic drugs (AEDs). After an 8-week baseline period, patients were randomized to once-daily placebo (n = 226), ESL 800 mg (n = 216), or ESL 1,200 mg (n = 211). Following a 2-week titration period, patients received ESL 800 or 1,200 mg once-daily for 12 weeks. Seizure data were captured and documented using event-entry or daily entry diaries. Results Standardized seizure frequency (SSF) during the maintenance period (primary end point) was reduced with ESL 1,200 mg (p = 0.004), and there was a trend toward improvement with ESL 800 mg (p = 0.06), compared with placebo. When data for titration and maintenance periods were combined, ESL 800 mg (p = 0.001) and 1,200 mg (p < 0.001) both reduced SSF. There were no statistically significant interactions between treatment response and geographical region (p = 0.38) or diary version (p = 0.76). Responder rate (≥50% reduction in SSF) was significantly higher with ESL 1,200 mg (42.6%, p < 0.001) but not ESL 800 mg (30.5%, p = 0.07) than placebo (23.1%). Incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation increased with ESL dose. The most common TEAEs were dizziness, somnolence, nausea, headache, and diplopia. Significance Adjunctive ESL 1,200 mg once-daily was more efficacious than placebo in adult patients with refractory partial-onset seizures. The once-daily 800 mg dose showed a marginal effect on SSF, but did not reach statistical significance. Both doses were well tolerated. Efficacy assessment was not affected by

  9. Muscular pre-conditioning using light-emitting diode therapy (LEDT) for high-intensity exercise: a randomized double-blind placebo-controlled trial with a single elite runner.

    PubMed

    Ferraresi, Cleber; Beltrame, Thomas; Fabrizzi, Fernando; do Nascimento, Eduardo Sanches Pereira; Karsten, Marlus; Francisco, Cristina de Oliveira; Borghi-Silva, Audrey; Catai, Aparecida Maria; Cardoso, Daniel Rodrigues; Ferreira, Antonio Gilberto; Hamblin, Michael R; Bagnato, Vanderlei Salvador; Parizotto, Nivaldo Antonio

    2015-07-01

    Recently, low-level laser (light) therapy (LLLT) has been used to improve muscle performance. This study aimed to evaluate the effectiveness of near-infrared light-emitting diode therapy (LEDT) and its mechanisms of action to improve muscle performance in an elite athlete. The kinetics of oxygen uptake (VO2), blood and urine markers of muscle damage (creatine kinase--CK and alanine), and fatigue (lactate) were analyzed. Additionally, some metabolic parameters were assessed in urine using proton nuclear magnetic resonance spectroscopy ((1)H NMR). A LED cluster with 50 LEDs (λ = 850 nm; 50 mW 15 s; 37.5 J) was applied on legs, arms and trunk muscles of a single runner athlete 5 min before a high-intense constant workload running exercise on treadmill. The athlete received either Placebo-1-LEDT; Placebo-2-LEDT; or Effective-LEDT in a randomized double-blind placebo-controlled trial with washout period of 7 d between each test. LEDT improved the speed of the muscular VO2 adaptation (∼-9 s), decreased O2 deficit (∼-10 L), increased the VO2 from the slow component phase (∼+348 ml min(-1)), and increased the time limit of exercise (∼+589 s). LEDT decreased blood and urine markers of muscle damage and fatigue (CK, alanine and lactate levels). The results suggest that a muscular pre-conditioning regimen using LEDT before intense exercises could modulate metabolic and renal function to achieve better performance. PMID:25585514

  10. Rapid response to methylphenidate as an add-on therapy to mirtazapine in the treatment of major depressive disorder in terminally ill cancer patients: a four-week, randomized, double-blinded, placebo-controlled study.

    PubMed

    Ng, Chong Guan; Boks, Marco P M; Roes, Kit C B; Zainal, Nor Zuraida; Sulaiman, Ahmad Hatim; Tan, Seng Beng; de Wit, Niek J

    2014-04-01

    This is a 4 week, randomized, double-blind, placebo-controlled study to examine the effects of methylphenidate as add-on therapy to mirtazapine compared to placebo for treatment of depression in terminally ill cancer patients. It involved 88 terminally ill cancer patients from University of Malaya Medical Centre, Kuala Lumpur, Malaysia. They were randomized and treated with either methylphenidate or placebo as add on to mirtazapine. The change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 3 was analyzed by linear regression. Changes of MADRS and Clinical Global Impression-Severity Scale (CGI-S) over 28 days were analyzed using mixed model repeated measures (MMRM). Secondary analysis of MADRS response rates, defined as 50% or more reduction from baseline score. A significantly larger reduction of Montgomery-Åsberg Depression Rating Scale (MADRS) score in the methylphenidate group was observed from day 3 (B=4.14; 95% CI=1.83-6.45). Response rate (defined as 50% or more reduction from baseline MADRS score) in the methylphenidate treated group was superior from day 14. Improvement in Clinical Global Impression-Severity Scale (CGI-S) was greater in the methylphenidate treated group from day 3 until day 28. The drop-out rates were 52.3% in the methylphenidate group and 59.1% in the placebo group (relative risk=0.86, 95%CI=0.54-1.37) due to cancer progression. Nervous system adverse events were more common in methylphenidate treated subjects (20.5% vs 9.1%, p=0.13). In conclusions, methylphenidate as add on therapy to mirtazapine demonstrated an earlier antidepressant response in terminally ill cancer patients, although at an increased risk of the nervous system side effects. PMID:24503279

  11. Design, conduct, and analyses of Breast International Group (BIG) 1-98: A randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer

    PubMed Central

    Giobbie-Hurder, Anita; Price, Karen N; Gelber, Richard D

    2010-01-01

    Background Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. Purpose To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. Methods From 1998–2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. Results The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. Limitations Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. Conclusions BIG 1-98 is an example of an enriched design, involving

  12. Preventive effect of Malva on urinary toxicity after radiation therapy in prostate cancer patients: A multi-centric, double-blind, randomized clinical trial

    PubMed Central

    Mofid, Bahram; Rezaeizadeh, Hossein; Jaladat, Amir Mohammad; Atarzadeh, Fatemeh; Moeini, Reihane; Motevalian, Abbas; Mosalaie, Ahmad; Farhan, Farshid; Rakhsha, Afshin; Kashi, Amir Shahram Yousefi

    2015-01-01

    Background: For patients receiving external beam radiation therapy (EBRT) after radical prostatectomy as adjuvant treatment or patients receiving EBRT as definitive treatment, partial irradiation of the urinary bladder is common. Many of such patients experience some degree of radiation-induced cystitis during or after EBRT. There is currently no efficient treatment for preventing radiation cystitis. Objective: The aim of this study was to evaluate the effectiveness of one of the safe mucilaginous herbs (Malva) in preventing radiation-induced dysuria in patients who are undergoing EBRT for prostate cancer. Methods: From April 2013 to August 2014, 68 patients were randomized into two groups using four block randomization, 34 to the drug (Malva) group and 34 to the placebo group. Of the 68 patients who began the study, 60 completed it. They were instructed to use the medication, i.e., Malva or the placebo, three times a day for six weeks. They were followed by a physician every two weeks for eight weeks, and urinary function was assessed in each visit by asking questions based on the Visual Prostate Symptom Score (VPSS) and a dysuria severity score. The changes in the VPSS and dysuria severity score between baseline and each follow-up visit were compared between the two groups in the study using repeated measures analysis of variance (ANOVA) and t-tests. Results: The median age of the 68 patients was 66. Twenty-one of 27 patients in the control group (77.7%) suffered from dysuria, while dysuria was detected in 23 of 33 patients (69.6%) who received Malva (odds ratio=2.70 for dysuria). After two weeks, four weeks, and six weeks of treatment with Malva, dysuria due to EBRT was milder in the treatment group than in the control group, and the differences were statistically significant (p = 0.005, p = 0.004, p = 0.001, respectively). Conclusion: To the best of our knowledge, our study is the first study to assess the protective effect of a mucilaginous herb (Malva

  13. Y2O3:Yb,Er@mSiO2-CuxS double-shelled hollow spheres for enhanced chemo-/photothermal anti-cancer therapy and dual-modal imaging

    NASA Astrophysics Data System (ADS)

    Yang, Dan; Yang, Guixin; Wang, Xingmei; Lv, Ruichan; Gai, Shili; He, Fei; Gulzar, Arif; Yang, Piaoping

    2015-07-01

    Multifunctional composites have gained significant interest due to their unique properties which show potential in biological imaging and therapeutics. However, the design of an efficient combination of multiple diagnostic and therapeutic modes is still a challenge. In this contribution, Y2O3:Yb,Er@mSiO2 double-shelled hollow spheres (DSHSs) with up-conversion fluorescence have been successfully prepared through a facile integrated sacrifice template method, followed by a calcination process. It is found that the double-shelled structure with large specific surface area and uniform shape is composed of an inner shell of luminescent Y2O3:Yb,Er and an outer mesoporous silica shell. Ultra small CuxS nanoparticles (about 2.5 nm) served as photothermal agents, and a chemotherapeutic agent (doxorubicin, DOX) was then attached onto the surface of mesoporous silica, forming a DOX-DSHS-CuxS composite. The composite exhibits high anti-cancer efficacy due to the synergistic photothermal therapy (PTT) induced by the attached CuxS nanoparticles and the enhanced chemotherapy promoted by the heat from the CuxS-based PTT when irradiated by 980 nm near-infrared (NIR) light. Moreover, the composite shows excellent in vitro and in vivo X-ray computed tomography (CT) and up-conversion fluorescence (UCL) imaging properties owing to the doped rare earth ions, thus making it possible to achieve the target of imaging-guided synergistic therapy.Multifunctional composites have gained significant interest due to their unique properties which show potential in biological imaging and therapeutics. However, the design of an efficient combination of multiple diagnostic and therapeutic modes is still a challenge. In this contribution, Y2O3:Yb,Er@mSiO2 double-shelled hollow spheres (DSHSs) with up-conversion fluorescence have been successfully prepared through a facile integrated sacrifice template method, followed by a calcination process. It is found that the double-shelled structure with large

  14. What is the ideal dose and power output of low-level laser therapy (810 nm) on muscle performance and post-exercise recovery? Study protocol for a double-blind, randomized, placebo-controlled trial

    PubMed Central

    2014-01-01

    Background Recent studies involving phototherapy applied prior to exercise have demonstrated positive results regarding the attenuation of muscle fatigue and the expression of biochemical markers associated with recovery. However, a number of factors remain unknown, such as the ideal dose and application parameters, mechanisms of action and long-term effects on muscle recovery. The aims of the proposed project are to evaluate the long-term effects of low-level laser therapy on post-exercise musculoskeletal recovery and identify the best dose andapplication power/irradiation time. Design and methods A double-blind, randomized, placebo-controlled clinical trial with be conducted. After fulfilling the eligibility criteria, 28 high-performance athletes will be allocated to four groups of seven volunteers each. In phase 1, the laser power will be 200 mW and different doses will be tested: Group A (2 J), Group B (6 J), Group C (10 J) and Group D (0 J). In phase 2, the best dose obtained in phase 1 will be used with the same distribution of the volunteers, but with different powers: Group A (100 mW), Group B (200 mW), Group C (400 mW) and Group D (0 mW). The isokinetic test will be performed based on maximum voluntary contraction prior to the application of the laser and after the eccentric contraction protocol, which will also be performed using the isokinetic dynamometer. The following variables related to physical performance will be analyzed: peak torque/maximum voluntary contraction, delayed onset muscle soreness (algometer), biochemical markers of muscle damage, inflammation and oxidative stress. Discussion Our intention, is to determine optimal laser therapy application parameters capable of slowing down the physiological muscle fatigue process, reducing injuries or micro-injuries in skeletal muscle stemming from physical exertion and accelerating post-exercise muscle recovery. We believe that, unlike drug therapy, LLLT has a biphasic dose–response pattern. Trial

  15. Cardiovascular, renal and gastrointestinal effects of incretin-based therapies: an acute and 12-week randomised, double-blind, placebo-controlled, mechanistic intervention trial in type 2 diabetes

    PubMed Central

    Smits, Mark M; Tonneijck, Lennart; Muskiet, Marcel H A; Hoekstra, Trynke; Kramer, Mark H H; Pieters, Indra C; Cahen, Djuna L; Diamant, Michaela; van Raalte, Daniël H

    2015-01-01

    Introduction Incretin-based therapies, that is, glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, are relatively novel antihyperglycaemic drugs that are frequently used in type 2 diabetes management. Apart from glucose-lowering, these agents exhibit pleiotropic actions that may have favourable and unfavourable clinical consequences. Incretin-based therapies have been associated with heart rate acceleration, heart failure, acute renal failure and acute pancreatitis. Conversely, these agents may reduce blood pressure, glomerular hyperfiltration, albuminuria and hepatic steatosis. While large-sized cardiovascular safety trials can potentially identify the clinical significance of some of these pleiotropic actions, small-sized mechanistic studies are important to understand the (patho)physiological rationale of these findings. The current protocol describes a mechanistic study to assess cardiovascular, renal and gastrointestinal effects, and mechanisms of incretin-based therapies in type 2 diabetes. Methods and analyses 60 patients with type 2 diabetes will undergo acute and prolonged randomised, double-blind, intervention studies. The acute intervention will consist of intravenous administration of the GLP-1 receptor agonist exenatide or placebo. For the prolonged intervention, patients will be randomised to 12-week treatment with the GLP-1 receptor agonist liraglutide, the DPP-4 inhibitor sitagliptin or matching placebos. For each examined organ system, a primary end point is defined. Primary cardiovascular end point is change in resting heart rate variability assessed by beat-to-beat heart rate monitor and spectral analyses software. Primary renal end point is change in glomerular filtration rate assessed by the classic inulin clearance methodology. Primary gastrointestinal end points are change in pancreatic exocrine function assessed by MRI-techniques (acute intervention) and faecal elastase-1 levels (12-week intervention

  16. The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients: A double-blind placebo-controlled prospective Phase III study by Radiation Therapy Oncology Group 9901

    SciTech Connect

    Ryu, Janice K. . E-mail: janice.ryu@ucdmc.ucdavis.edu; Swann, Suzanne; LeVeque, Francis; Johnson, Darlene J.; Chen, Allan; Fortin, Andre; Kim, Harold; Ang, Kian K.

    2007-03-01

    Purpose: Based on early clinical evidence of potential mucosal protection by granulocyte-macrophage colony stimulating factor (GM-CSF), the Radiation Therapy Oncology Group conducted a double-blind, placebo-controlled, randomized study to test the efficacy and safety of GM-CSF in reducing the severity and duration of mucosal injury and pain (mucositis) associated with curative radiotherapy (RT) in head-and-neck cancer patients. Methods and Materials: Eligible patients included those with head-and-neck cancer with radiation ports encompassing >50% of oral cavity and/or oropharynx. Standard RT ports were used to cover the primary tumor and regional lymphatics at risk in standard fractionation to 60-70 Gy. Concurrent cisplatin chemotherapy was allowed. Patients were randomized to receive subcutaneous injection of GM-CSF 250 {mu}g/m{sup 2} or placebo 3 times a week. Mucosal reaction was assessed during the course of RT using the National Cancer Institute Common Toxicity Criteria and the protocol-specific scoring system. Results: Between October 2000 and September 2002, 130 patients from 36 institutions were accrued. Nine patients (7%) were excluded from the analysis, 3 as a result of drug unavailability. More than 80% of the patients participated in the quality-of-life endpoint of this study. The GM-CSF did not cause any increase in toxicity compared with placebo. There was no statistically significant difference in the average mean mucositis score in the GM-CSF and placebo arms by a t test (p = 0.4006). Conclusion: This placebo-controlled, randomized study demonstrated no significant effect of GM-CSF given concurrently compared with placebo in reducing the severity or duration of RT-induced mucositis in patients undergoing definitive RT for head-and-neck cancer.

  17. The effect of ubiquinone and combined antioxidant therapy on oxidative stress markers in non-proliferative diabetic retinopathy: A phase IIa, randomized, double-blind, and placebo-controlled study.

    PubMed

    Rodríguez-Carrizalez, Adolfo Daniel; Castellanos-González, José Alberto; Martínez-Romero, Esaú César; Miller-Arrevillaga, Guillermo; Pacheco-Moisés, Fermín Paul; Román-Pintos, Luis Miguel; Miranda-Díaz, Alejandra Guillermina

    2016-07-01

    Objective To evaluate the effect of ubiquinone (Coenzyme Q10) and combined antioxidant therapy (CAT) on oxidative stress markers in non-proliferative diabetic retinopathy (NPDR) under clinical management. Study design In a randomized, double-blind, phase IIa, placebo-controlled, clinical trial, three study groups were formed and administered medications as follows: Group 1, Coenzyme Q10; Group 2, CAT; and Group 3, placebo. Methods Serum levels of the products of lipid peroxidation (LPO) and nitrites/nitrates, as markers of oxidative/nitrosative stress, were measured. As antioxidants, the total antioxidant capacity (TAC), catalase activity, and glutathione peroxidase (GPx) activity were measured. Results Baseline serum levels of LPO and nitrites/nitrates were significantly elevated in the three groups vs. healthy group (P < 0.0001), while final levels in the Coenzyme Q10 and CAT groups were decreased vs. normal levels (P < 0.0001). The baseline TAC was consumed in the three groups (P < 0.0001), while final results in the Coenzyme Q10 and CAT groups improved (P < 0.0001). Baseline catalase activity was increased in all groups vs. normal values (P < 0.001), while final levels in the Coenzyme Q10 (P < 0.001) and CAT groups (P < 0.0001) were decreased. GPx behaved similarly to catalase and improved in the final results (P < 0.0001). Discussion Adjunctive antioxidant treatment for 6 months was effective and safe for improving the oxidative stress in NPDR. PMID:26321469

  18. Seeing Double

    NASA Astrophysics Data System (ADS)

    Pesic, Peter

    2003-10-01

    The separateness and connection of individuals is perhaps the central question of human life: What, exactly, is my individuality? To what degree is it unique? To what degree can it be shared, and how? To the many philosophical and literary speculations about these topics over time, modern science has added the curious twist of quantum theory, which requires that the elementary particles of which everything consists have no individuality at all. All aspects of chemistry depend on this lack of individuality, as do many branches of physics. From where, then, does our individuality come? In Seeing Double, Peter Pesic invites readers to explore this intriguing set of questions. He draws on literary and historical examples that open the mind (from Homer to Martin Guerre to Kafka), philosophical analyses that have helped to make our thinking and speech more precise, and scientific work that has enabled us to characterize the phenomena of nature. Though he does not try to be all-inclusive, Pesic presents a broad range of ideas, building toward a specific point of view: that the crux of modern quantum theory is its clash with our ordinary concept of individuality. This represents a departure from the usual understanding of quantum theory. Pesic argues that what is bizarre about quantum theory becomes more intelligible as we reconsider what we mean by individuality and identity in ordinary experience. In turn, quantum identity opens a new perspective on us. Peter Pesic is a Tutor and Musician-in-Residence at St. John's College, Santa Fe, New Mexico. He has a Ph.D. in physics from Stanford University.

  19. Double inflation

    SciTech Connect

    Silk, J.; Turner, M.S.

    1986-04-01

    The Zel'dovich spectrum of adiabatic density perturbations is a generic prediction of inflation. There is increasing evidence that when the spectrum is normalized by observational data on small scales, there is not enough power on large scales to account for the observed large-scale structure in the Universe. Decoupling the spectrum on large and small scales could solve this problem. As a means of decoupling the large and small scales we propose double inflation (i.e., two episodes of inflation). In this scenario the spectrum on large scales is determined by the first episode of inflation and those on small scales by a second episode of inflation. We present three models for such a scenario. By nearly saturating the large angular-scale cosmic microwave anisotropy bound, we can easily account for the observed large-scale structure. We take the perturbations on small scales to be very large, deltarho/rho approx. = 0.1 to 0.01, which results in the production of primordial black holes (PBHs), early formation of structure, reionization of the Universe, and a rich array of astrophysical events. The ..cap omega..-problem is also addressed by our scenario. Allowing the density perturbations produced by the second episode of inflation to be large also lessens the fine-tuning required in the scalar potential and makes reheating much easier. We briefly speculate on the possibility that the second episode of inflation proceeds through the nucleation of bubbles, which today manifest themselves as empty bubbles whose surfaces are covered with galaxies. 37 refs., 1 fig.

  20. Laparoscopic resection of a gastrointestinal stromal tumor of the lower rectum in a patient with coronary artery disease following long-term neoadjuvant imatinib treatment and anticoagulation therapy

    PubMed Central

    2014-01-01

    Surgery is the mainstay of treatment for gastrointestinal stromal tumors (GISTs). However, complete resection of rectal GISTs is sometimes difficult because of bulkiness and/or anatomical reasons. Neoadjuvant imatinib therapy has gained attention as an alternative treatment to increase the chance of en bloc resection of rectal GISTs, although it usually takes several months. In this case report, we first demonstrated that neoadjuvant imatinib therapy can be performed safely not only to downsize tumors, but also to allow adequate time for the effective treatment of major comorbid illnesses. A 74-year-old man was diagnosed with a 45 mm GIST of the lower rectum. He also had severe stenosis in the proximal segment of the left anterior descending coronary artery. Following the implantation of a drug-eluting stent, the patient received imatinib together with dual anti-platelet therapy for 12 months without obvious side effects. Follow-up image studies revealed tumor shrinkage as well as stent patency. En bloc resection of the GIST was performed laparoscopically, which preserved the anus. The patient is currently alive without any evidence of relapse for 12 months after surgery. PMID:25022862

  1. PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages - a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation.

    PubMed Central

    Coomarasamy, Arri; Williams, Helen; Truchanowicz, Ewa; Seed, Paul T; Small, Rachel; Quenby, Siobhan; Gupta, Pratima; Dawood, Feroza; Koot, Yvonne E; Atik, Ruth Bender; Bloemenkamp, Kitty Wm; Brady, Rebecca; Briley, Annette; Cavallaro, Rebecca; Cheong, Ying C; Chu, Justin; Eapen, Abey; Essex, Holly; Ewies, Ayman; Hoek, Annemieke; Kaaijk, Eugenie M; Koks, Carolien A; Li, Tin-Chiu; MacLean, Marjory; Mol, Ben W; Moore, Judith; Parrott, Steve; Ross, Jackie A; Sharpe, Lisa; Stewart, Jane; Trépel, Dominic; Vaithilingam, Nirmala; Farquharson, Roy G; Kilby, Mark David; Khalaf, Yacoub; Goddijn, Mariëtte; Regan, Lesley; Rai, Rajendra

    2016-01-01

    BACKGROUND AND OBJECTIVES Progesterone is essential to maintain a healthy pregnancy. Guidance from the Royal College of Obstetricians and Gynaecologists and a Cochrane review called for a definitive trial to test whether or not progesterone therapy in the first trimester could reduce the risk of miscarriage in women with a history of unexplained recurrent miscarriage (RM). The PROMISE trial was conducted to answer this question. A concurrent cost-effectiveness analysis was conducted. DESIGN AND SETTING A randomised, double-blind, placebo-controlled, international multicentre study, with economic evaluation, conducted in hospital settings across the UK (36 sites) and in the Netherlands (nine sites). PARTICIPANTS AND INTERVENTIONS Women with unexplained RM (three or more first-trimester losses), aged between 18 and 39 years at randomisation, conceiving naturally and giving informed consent, received either micronised progesterone (Utrogestan(®), Besins Healthcare) at a dose of 400 mg (two vaginal capsules of 200 mg) or placebo vaginal capsules twice daily, administered vaginally from soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) until 12 completed weeks of gestation (or earlier if the pregnancy ended before 12 weeks). MAIN OUTCOME MEASURES Live birth beyond 24 completed weeks of gestation (primary outcome), clinical pregnancy at 6-8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use. METHODS Participants were randomised after confirmation of pregnancy. Randomisation was performed online via a secure internet facility. Data were collected on four occasions of outcome assessment after randomisation, up to 28 days after birth. RESULTS A total of 1568 participants were screened for eligibility. Of the 836 women randomised between 2010 and 2013, 404 received progesterone and 432 received placebo. The baseline data (age, body

  2. A randomised, double-masked phase III/IV study of the efficacy and safety of Avastin® (Bevacizumab) intravitreal injections compared to standard therapy in subjects with choroidal neovascularisation secondary to age-related macular degeneration: clinical trial design

    PubMed Central

    Patel, Praveen J; Bunce, Catey; Tufail, Adnan

    2008-01-01

    Background The management of neovascular age-related macular degeneration (nAMD) has been transformed by the introduction of agents delivered by intravitreal injection which block the action of vascular endothelial growth factor-A (anti-VEGF agents). One such agent in widespread use is bevacizumab which was initially developed for use in oncology. Most of the evidence supporting the use of bevacizumab for nAMD has come from interventional case series and this clinical trial was initiated because of the increasing and widespread use of this agent in the treatment of nAMD (an off-label indication) despite a lack of definitive unbiased safety and efficacy data. Methods and design The Avastin® (bevacizumab) for choroidal neovascularisation (ABC) trial is a double-masked randomised controlled trial comparing intravitreal bevacizumab injections to standard therapy in the treatment of nAMD. Patients are randomised to intravitreal bevacizumab or standard therapy available at the time of trial initiation (verteporfin photodynamic therapy, intravitreal pegaptanib or sham treatment). Ranibizumab treatment was not included in the control arm as it had not been licensed for use at the start of recruitment for this trial. The primary outcome is the proportion of patients gaining ≥ 15 letters of visual acuity at 1 year and secondary outcomes include the proportion of patients with stable vision and mean visual acuity change. Discussion The ABC Trial is the first double-masked randomised control trial to investigate the efficacy and safety of intravitreal bevacizumab in the treatment of nAMD. This trial fully recruited in November 2007 and results should be available in early 2009. Important design issues for this clinical trial include (a) defining the control group (b) use of gain in vision as primary efficacy end-point and (c) use of pro re nata treatment using intravitreal bevacizumab rather than continuous therapy. Trial registration Current controlled trials ISRCTN

  3. A double-double/double-single computation package

    SciTech Connect

    Bailey, David H.

    2004-12-01

    The DDFUNIDSFUN software permits a new or existing Fortran-90 program to utilize double-double precision (approx. 31 digits) or double-single precision (approx. 14 digits) arithmetic. Double-double precision is required by a rapidly expandirtg body of scientific computations in physics and mathematics, for which the conventional 64-bit IEEE computer arithmetic (about 16 decimal digit accuracy) is not sufficient. Double-single precision permits users of systems that do not have hardware 64-bit IEEE arithmetic (such as some game systems) to perform arithmetic at a precision nearly as high as that of systems that do. Both packages run significantly faster Than using multiple precision or arbitrary precision software for this purpose. The package includes an extensive set of low-level routines to perform high-precision arithmetic, including routines to calculate various algebraic and transcendental functions, such as square roots, sin, ccc, exp, log and others. In addition, the package includes high-level translation facilities, so that Fortran programs can utilize these facilities by making only a few changes to conventional Fortran programs. In most cases, the only changes that are required are to change the type statements of variables that one wishes to be treated as multiple precision, plus a few other minor changes. The DDFUN package is similar in functionality to the double-double part of the GD package, which was previously written at LBNL. However, the DDFUN package is written exclusively in Fortran-90, thus avoidIng difficulties that some users experience when using GD, which includes both Fortran-90 and C++ code.

  4. A double-double/double-single computation package

    Energy Science and Technology Software Center (ESTSC)

    2004-12-01

    The DDFUNIDSFUN software permits a new or existing Fortran-90 program to utilize double-double precision (approx. 31 digits) or double-single precision (approx. 14 digits) arithmetic. Double-double precision is required by a rapidly expandirtg body of scientific computations in physics and mathematics, for which the conventional 64-bit IEEE computer arithmetic (about 16 decimal digit accuracy) is not sufficient. Double-single precision permits users of systems that do not have hardware 64-bit IEEE arithmetic (such as some game systems)more » to perform arithmetic at a precision nearly as high as that of systems that do. Both packages run significantly faster Than using multiple precision or arbitrary precision software for this purpose. The package includes an extensive set of low-level routines to perform high-precision arithmetic, including routines to calculate various algebraic and transcendental functions, such as square roots, sin, ccc, exp, log and others. In addition, the package includes high-level translation facilities, so that Fortran programs can utilize these facilities by making only a few changes to conventional Fortran programs. In most cases, the only changes that are required are to change the type statements of variables that one wishes to be treated as multiple precision, plus a few other minor changes. The DDFUN package is similar in functionality to the double-double part of the GD package, which was previously written at LBNL. However, the DDFUN package is written exclusively in Fortran-90, thus avoidIng difficulties that some users experience when using GD, which includes both Fortran-90 and C++ code.« less

  5. The Cambridge Double Star Atlas

    NASA Astrophysics Data System (ADS)

    MacEvoy, Bruce; Tirion, Wil

    2015-12-01

    Preface; What are double stars?; The binary orbit; Double star dynamics; Stellar mass and the binary life cycle; The double star population; Detecting double stars; Double star catalogs; Telescope optics; Preparing to observe; Helpful accessories; Viewing challenges; Next steps; Appendices: target list; Useful formulas; Double star orbits; Double star catalogs; The Greek alphabet.

  6. Double outlet right ventricle

    MedlinePlus

    ... medlineplus.gov/ency/article/007328.htm Double outlet right ventricle To use the sharing features on this page, please enable JavaScript. Double outlet right ventricle (DORV) is a heart disease that is ...

  7. Chromosome doubling method

    DOEpatents

    Kato, Akio

    2006-11-14

    The invention provides methods for chromosome doubling in plants. The technique overcomes the low yields of doubled progeny associated with the use of prior techniques for doubling chromosomes in plants such as grasses. The technique can be used in large scale applications and has been demonstrated to be highly effective in maize. Following treatment in accordance with the invention, plants remain amenable to self fertilization, thereby allowing the efficient isolation of doubled progeny plants.

  8. Double crush syndrome in the lower extremity: a case report.

    PubMed

    Borgia, Anthony V; Hruska, Jerome K; Braun, Karina

    2012-01-01

    Upton and McComas first described double crush syndrome in 1973. The theory behind double crush syndrome postulated that a proximal lesion in a nerve would make that same nerve more vulnerable to additional distal lesions. Many of the studies investigating the possibility of the double crush syndrome involve lesions in the upper extremity with very few articles written specifically about double crush syndrome in the lower extremity. We present the case of a 33-year-old massage therapist who uses her feet to provide therapy to clients who presented to our clinic with symptoms consistent with tarsal tunnel syndrome. Her failure to progress in a satisfactory manner after a variety of therapies made us search for additional etiologies for her foot pain. In cases where tarsal tunnel persists after surgical therapy, the treating physician should search for more proximal lesions along the course of the nerve. PMID:22826333

  9. Efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide added to insulin therapy in poorly regulated patients with type 1 diabetes—a protocol for a randomised, double-blind, placebo-controlled study: The Lira-1 study

    PubMed Central

    Dejgaard, Thomas Fremming; Knop, Filip Krag; Tarnow, Lise; Frandsen, Christian Seerup; Hansen, Tanja Stenbæk; Almdal, Thomas; Holst, Jens Juul; Madsbad, Sten; Andersen, Henrik Ullits

    2015-01-01

    Introduction Intensive insulin therapy is recommended for the treatment of type 1 diabetes (T1D). Hypoglycaemia and weight gain are the common side effects of insulin treatment and may reduce compliance. In patients with insulin-treated type 2 diabetes, the addition of glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy has proven effective in reducing weight gain and insulin dose. The present publication describes a protocol for a study evaluating the efficacy and safety of adding a GLP-1RA to insulin treatment in overweight patients with T1D in a randomised, double-blinded, controlled design. Methods and analysis In total, 100 patients with type 1 diabetes, poor glycaemic control (glycated haemoglobin (HbA1c) >8%) and overweight (body mass index >25 kg/m2) will be randomised to either liraglutide 1.8 mg once daily or placebo as an add-on to intensive insulin therapy in this investigator initiated, double-blinded, placebo-controlled parallel study. The primary end point is glycaemic control as measured by changes in HbA1c. Secondary end points include changes in the insulin dose, hypoglyacemic events, body weight, lean body mass, fat mass, food preferences and adverse events. Glycaemic excursions, postprandial glucagon levels and gastric emptying rate during a standardised liquid meal test will also be studied. Ethics and dissemination The study is approved by the Danish Medicines Authority, the Regional Scientific-Ethical Committee of the Capital Region of Denmark and the Data Protection Agency. The study will be carried out under the surveillance and guidance of the good clinical practice (GCP) unit at Copenhagen University Hospital Bispebjerg in accordance with the ICH-GCP guidelines and the Helsinki Declaration. Trial registration number NCT01612468. PMID:25838513

  10. Observing Double Stars

    NASA Astrophysics Data System (ADS)

    Genet, Russell M.; Fulton, B. J.; Bianco, Federica B.; Martinez, John; Baxter, John; Brewer, Mark; Carro, Joseph; Collins, Sarah; Estrada, Chris; Johnson, Jolyon; Salam, Akash; Wallen, Vera; Warren, Naomi; Smith, Thomas C.; Armstrong, James D.; McGaughey, Steve; Pye, John; Mohanan, Kakkala; Church, Rebecca

    2012-05-01

    Double stars have been systematically observed since William Herschel initiated his program in 1779. In 1803 he reported that, to his surprise, many of the systems he had been observing for a quarter century were gravitationally bound binary stars. In 1830 the first binary orbital solution was obtained, leading eventually to the determination of stellar masses. Double star observations have been a prolific field, with observations and discoveries - often made by students and amateurs - routinely published in a number of specialized journals such as the Journal of Double Star Observations. All published double star observations from Herschel's to the present have been incorporated in the Washington Double Star Catalog. In addition to reviewing the history of visual double stars, we discuss four observational technologies and illustrate these with our own observational results from both California and Hawaii on telescopes ranging from small SCTs to the 2-meter Faulkes Telescope North on Haleakala. Two of these technologies are visual observations aimed primarily at published "hands-on" student science education, and CCD observations of both bright and very faint doubles. The other two are recent technologies that have launched a double star renaissance. These are lucky imaging and speckle interferometry, both of which can use electron-multiplying CCD cameras to allow short (30 ms or less) exposures that are read out at high speed with very low noise. Analysis of thousands of high speed exposures allows normal seeing limitations to be overcome so very close doubles can be accurately measured.

  11. Isolation of Bioactive Compounds That Relate to the Anti-Platelet Activity of Cymbopogon ambiguus

    PubMed Central

    Grice, I. Darren; Rogers, Kelly L.; Griffiths, Lyn R.

    2011-01-01

    Infusions and decoctions of Cymbopogon ambiguus have been used traditionally in Australia for the treatment of headache, chest infections and muscle cramps. The aim of the present study was to screen and identify bioactive compounds from C. ambiguus that could explain this plant's anti-headache activity. A dichloromethane extract of C. ambiguus was identified as having activity in adenosine-diphosphate-induced human platelet aggregation and serotonin-release inhibition bioassays. Subsequent fractionation of this extract led to the isolation of four phenylpropenoids, eugenol, elemicin, eugenol methylether and trans-isoelemicin. While both eugenol and elemicin exhibited dose-dependent inhibition of ADP-induced human platelet serotonin release, only eugenol displayed potent inhibitory activity with an IC50 value of 46.6 μM, in comparison to aspirin, with an IC50 value of 46.1 μM. These findings provide evidence to support the therapeutic efficacy of C. ambiguus in the non-conventional treatment of headache and inflammatory conditions. PMID:20047890

  12. The Constituents of Roots and Stems of Illigera luzonensis and Their Anti-Platelet Aggregation Effects

    PubMed Central

    Huang, Chieh-Hung; Chan, Yu-Yi; Kuo, Ping-Chung; Chen, Yu-Fon; Chang, Ren-Jie; Chen, Ih-Sheng; Wu, Shwu-Jen; Wu, Tian-Shung

    2014-01-01

    Phytochemical investigation of the roots and stems of Illigera luzonensis afforded two new aporphine alkaloids (1) and (2), one new bisdehydroaporphine alkaloid (3), and one new benzenoid (4), along with 28 known structures. The structures of new compounds were elucidated by spectral and MS analysis. Among the isolated compounds, (1) and (4–13) were subjected into the examination for their inhibitory effects on the aggregation of washed rabbit platelets. PMID:25089876

  13. [Coumarins from Leonurus japonicus and their anti-platelet aggregative activity].

    PubMed

    Yang, Huai; Zhou, Qin-mei; Peng, Cheng; Liu, Lu-si; Xie, Xiao-fang; Xiong, Liang; Liu, Zhao-hua

    2014-11-01

    Chemical constituents of Leonurus japonicus were isolated and purified by a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, MCI, and Rp C18. Structures of the isolates were determined by spectroscopic analysis as 10 coumarins: bergapten (1), xanthotoxin (2), isopimpinellin (3), isogosferal (4), imperatorin (5), meransin hydrate(6), isomeranzin(7), murrayone(8) , auraptenol(9), and osthol(10). In addition to compound 9, the others were isolated from the genus Leonurus for the first time. In the in vitro assay, compounds 4 and 8 significantly inhibited the abnormal increase of platelet aggregation induced by ADP. PMID:25850267

  14. Radiolabeled anti platelet monoclonal antibody for imaging in-vivo thrombi

    SciTech Connect

    Srivastava, S.C.; Coller, B.S.; Meinken, G.E.

    1993-07-06

    A radiolabeled monoclonal antibody radiolabeled with a halogen or metallic radionuclide selected from the group consisting of [sup 123]I, [sup 125]I, [sup 131]I, [sup 111]In-DTPA, [sup 99]mTc and [sup 97]Ru, wherein the monoclonal antibody is of the class IgG, produced by a hybridoma formed by fusion of cells from a BALB/C mouse myeloma line, X63.Ag8.653 and spleen cells from a BALB/c mouse previously immunized with human blood platelets, which antibody: (a) reacts readily with normal human platelets and with dog platelets; (b) fails to react with thrombasthenic human platelets or human platelets whose GPIIb/IIIa complex is dissociated with EDTA and (c) reacts slowly with inactivated platelets and substantially twice as rapidly with ADP activated platelets; and (d) completely blocks the interaction of fibrinogen with platelets induced by ADP.

  15. Study protocol of Prednisone in episodic Cluster Headache (PredCH): a randomized, double-blind, placebo-controlled parallel group trial to evaluate the efficacy and safety of oral prednisone as an add-on therapy in the prophylactic treatment of episodic cluster headache with verapamil

    PubMed Central

    2013-01-01

    Background Episodic cluster headache (ECH) is a primary headache disorder that severely impairs patient’s quality of life. First-line therapy in the initiation of a prophylactic treatment is verapamil. Due to its delayed onset of efficacy and the necessary slow titration of dosage for tolerability reasons prednisone is frequently added by clinicians to the initial prophylactic treatment of a cluster episode. This treatment strategy is thought to effectively reduce the number and intensity of cluster attacks in the beginning of a cluster episode (before verapamil is effective). This study will assess the efficacy and safety of oral prednisone as an add-on therapy to verapamil and compare it to a monotherapy with verapamil in the initial prophylactic treatment of a cluster episode. Methods and design PredCH is a prospective, randomized, double-blind, placebo-controlled trial with parallel study arms. Eligible patients with episodic cluster headache will be randomized to a treatment intervention with prednisone or a placebo arm. The multi-center trial will be conducted in eight German headache clinics that specialize in the treatment of ECH. Discussion PredCH is designed to assess whether oral prednisone added to first-line agent verapamil helps reduce the number and intensity of cluster attacks in the beginning of a cluster episode as compared to monotherapy with verapamil. Trial registration German Clinical Trials Register DRKS00004716 PMID:23889923

  16. Topological Quantum Double

    NASA Astrophysics Data System (ADS)

    Bonneau, Philippe

    Following a preceding paper showing how the introduction of a t.v.s. topology on quantum groups led to a remarkable unification and rigidification of the different definitions, we adapt here, in the same way, the definition of quantum double. This topological double is dualizable and reflexive (even for infinite dimensional algebras). In a simple case we show, considering the double as the "zero class" of an extension theory, the uniqueness of the double structure as a quasi-Hopf algebra. A la suite d'un précédent article montrant comment l'introduction d'une topologie d'e.v.t. sur les groupes quantiques permet une unification et une rigidification remarquables des différentes définitions, on adapte ici de la même manière la définition du double quantique. Ce double topologique est alors dualisable et reflexif (même pour des algèbres de dimension infinie). Dans un cas simple on montre, en considérant le double comme la "classe zéro" d'une théorie d'extensions, l'unicité de cette structure comme algèbre quasi-Hopf.

  17. Emerging double helical nanostructures

    NASA Astrophysics Data System (ADS)

    Zhao, Meng-Qiang; Zhang, Qiang; Tian, Gui-Li; Wei, Fei

    2014-07-01

    As one of the most important and land-mark structures found in nature, a double helix consists of two congruent single helices with the same axis or a translation along the axis. This double helical structure renders the deoxyribonucleic acid (DNA) the crucial biomolecule in evolution and metabolism. DNA-like double helical nanostructures are probably the most fantastic yet ubiquitous geometry at the nanoscale level, which are expected to exhibit exceptional and even rather different properties due to the unique organization of the two single helices and their synergistic effect. The organization of nanomaterials into double helical structures is an emerging hot topic for nanomaterials science due to their promising exceptional unique properties and applications. This review focuses on the state-of-the-art research progress for the fabrication of double-helical nanostructures based on `bottom-up' and `top-down' strategies. The relevant nanoscale, mesoscale, and macroscopic scale fabrication methods, as well as the properties of the double helical nanostructures are included. Critical perspectives are devoted to the synthesis principles and potential applications in this emerging research area. A multidisciplinary approach from the scope of nanoscience, physics, chemistry, materials, engineering, and other application areas is still required to the well-controlled and large-scale synthesis, mechanism, property, and application exploration of double helical nanostructures.

  18. Efficacy and safety of fixed-dose combination therapy with olmesartan medoxomil and rosuvastatin in Korean patients with mild to moderate hypertension and dyslipidemia: an 8-week, multicenter, randomized, double-blind, factorial-design study (OLSTA-D RCT: OLmesartan rosuvaSTAtin from Daewoong).

    PubMed

    Park, Jin-Sun; Shin, Joon-Han; Hong, Taek-Jong; Seo, Hong-Seog; Shim, Wan-Joo; Baek, Sang-Hong; Jeong, Jin-Ok; Ahn, Youngkeun; Kang, Woong-Chol; Kim, Young-Hak; Kim, Sang-Hyun; Hyon, Min-Su; Choi, Dong-Hoon; Nam, Chang-Wook; Park, Tae-Ho; Lee, Sang-Chol; Kim, Hyo-Soo

    2016-01-01

    The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance. This study aimed to evaluate the efficacy and safety of fixed-dose combination (FDC) therapy with olmesartan medoxomil (40 mg) and rosuvastatin (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. This multicenter, randomized, double-blind, factorial-design study included patients aged ≥20 years with mild to moderate essential hypertension and dyslipidemia. Patients were randomly assigned to receive FDC therapy (40 mg olmesartan medoxomil, 20 mg rosuvastatin), 40 mg olmesartan medoxomil, 20 mg rosuvastatin, or a placebo. The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil, and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment. A total of 162 patients were included. The least square mean percentage change (standard error) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group (-52.3% [2.8%] vs -0.6% [3.5%], P<0.0001), and the difference was -51.7% (4.1%) (95% confidence interval: -59.8% to -43.6%). The least square mean change (standard error) from baseline in diastolic blood pressure 8 weeks after treatment was significantly greater in the FDC group than in the rosuvastatin group (-10.4 [1.2] mmHg vs 0.1 [1.6] mmHg, P<0.0001), and the difference was -10.5 (1.8) mmHg (95% confidence interval: -14.1 to -6.9 mmHg). There were 50 adverse events in 41 patients (22.7%) and eight adverse drug reactions in five patients (2.8%). The study found that FDC therapy with olmesartan medoxomil and rosuvastatin is an effective, safe treatment for patients with hypertension and dyslipidemia. This combination may improve medication compliance in patients with a large pill burden. PMID

  19. Efficacy and safety of fixed-dose combination therapy with olmesartan medoxomil and rosuvastatin in Korean patients with mild to moderate hypertension and dyslipidemia: an 8-week, multicenter, randomized, double-blind, factorial-design study (OLSTA-D RCT: OLmesartan rosuvaSTAtin from Daewoong)

    PubMed Central

    Park, Jin-Sun; Shin, Joon-Han; Hong, Taek-Jong; Seo, Hong-Seog; Shim, Wan-Joo; Baek, Sang-Hong; Jeong, Jin-Ok; Ahn, Youngkeun; Kang, Woong-Chol; Kim, Young-Hak; Kim, Sang-Hyun; Hyon, Min-Su; Choi, Dong-Hoon; Nam, Chang-Wook; Park, Tae-Ho; Lee, Sang-Chol; Kim, Hyo-Soo

    2016-01-01

    The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance. This study aimed to evaluate the efficacy and safety of fixed-dose combination (FDC) therapy with olmesartan medoxomil (40 mg) and rosuvastatin (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. This multicenter, randomized, double-blind, factorial-design study included patients aged ≥20 years with mild to moderate essential hypertension and dyslipidemia. Patients were randomly assigned to receive FDC therapy (40 mg olmesartan medoxomil, 20 mg rosuvastatin), 40 mg olmesartan medoxomil, 20 mg rosuvastatin, or a placebo. The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil, and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment. A total of 162 patients were included. The least square mean percentage change (standard error) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group (−52.3% [2.8%] vs −0.6% [3.5%], P<0.0001), and the difference was −51.7% (4.1%) (95% confidence interval: −59.8% to −43.6%). The least square mean change (standard error) from baseline in diastolic blood pressure 8 weeks after treatment was significantly greater in the FDC group than in the rosuvastatin group (−10.4 [1.2] mmHg vs 0.1 [1.6] mmHg, P<0.0001), and the difference was −10.5 (1.8) mmHg (95% confidence interval: −14.1 to −6.9 mmHg). There were 50 adverse events in 41 patients (22.7%) and eight adverse drug reactions in five patients (2.8%). The study found that FDC therapy with olmesartan medoxomil and rosuvastatin is an effective, safe treatment for patients with hypertension and dyslipidemia. This combination may improve medication compliance in patients with a large

  20. Efficacy and Safety Investigation of Kuntai Capsule for the Add-back Therapy of Gonadotropin Releasing Hormone Agonist Administration to Endometriosis Patients: A Randomized, Double-blind, Blank- and Tibolone-controlled Study

    PubMed Central

    Chen, Ji-Ming; Gao, Hong-Yan; Ding, Yi; Yuan, Xia; Wang, Qing; Li, Qin; Jiang, Guo-Hua

    2015-01-01

    Background: As a Chinese Traditional Medicine product, Kuntai capsule could improve the peri-menopausal symptoms in postmenopausal women. But it is still not clear whether Kuntai capsule has a good effect on alleviating peri-menopausal symptoms induced by gonadotropin releasing hormone agonist (GnRH-a) treatment. The purpose of this study was to investigate the clinical effectiveness and safety of Kuntai capsule, on peri-menopausal symptoms in endometriosis (EMS) patients, with postoperative GnRH-a treatment. Methods: Ninety EMS ovarian cyst women with postoperative GnRH-a administration were enrolled in the study, and were randomly divided into Kuntai group, Tibolone group, or blank Control group. The therapeutic strategy in Kuntai group was 4 Kuntai capsules tid,po for 12 weeks after the first GnRH-a injection, while Tibolone 2.5 mg qd, po for 12 weeks in Tibolone group. There was no drug addition in Control group. Climacteric complaints were evaluated by Kupperman menopausal index (KMI) and hot flash/sweating score. Liver and renal functions, lipid profile, serum sex hormone levels and endometrial thickness were measured, and the frequency of adverse events in Kuntai and Tibolone groups was recorded. Results: (1) Before GnRH-a therapy, the baseline parameter results were comparable in the three groups (P > 0.05). (2) After GnRH-a therapy, KMI and hot flash/sweating scores in all the three groups increased significantly (P < 0.05). At the 4th week after GnRH-a therapy, KMI and hot flash/sweating score results were as follows: Control group > Kuntai group > Tibolone group (P < 0.05); at the 8th and 12th week after GnRH-a therapy, KMI and hot flash/sweating score in Control group were significantly higher than the other two groups (P < 0.05), and no significant difference was identified between Kuntai and Tibolone group (P > 0.05). (3) No statistical change took place in the liver and renal functions and lipid profile in all the three groups after the treatment (P

  1. Double Degenerate Binary Systems

    SciTech Connect

    Yakut, K.

    2011-09-21

    In this study, angular momentum loss via gravitational radiation in double degenerate binary (DDB)systems (NS + NS, NS + WD, WD + WD, and AM CVn) is studied. Energy loss by gravitational waves has been estimated for each type of systems.

  2. Double aortic arch

    MedlinePlus

    ... double aortic arch may press on the windpipe (trachea) and esophagus, leading to trouble breathing and swallowing. ... to relieve pressure on the esophagus and windpipe (trachea). The surgeon ties off the smaller branch and ...

  3. Exploring the effect of space and place on response to exercise therapy for knee and hip pain—a protocol for a double-blind randomised controlled clinical trial: the CONEX trial

    PubMed Central

    Thorlund, Jonas Bloch; Ulrich, Roger S; Dieppe, Paul A; Roos, Ewa M

    2015-01-01

    Introduction Context effects are described as effects of a given treatment, not directly caused by the treatment itself, but rather caused by the context in which treatment is delivered. Exercise is a recommended core treatment in clinical guidelines for musculoskeletal disorders. Although moderately effective overall, variation is seen in size of response to exercise across randomised controlled trial (RCT) studies. Part of this variation may be related to the fact that exercise interventions are performed in different physical environments, which may affect participants differently. The study aims to investigate the effect of exercising in a contextually enhanced physical environment for 8 weeks in people with knee or hip pain. Methods and analysis The study is a double-blind RCT. Eligible participants are 35 years or older with persisting knee and/or hip pain for 3 months. Participants are randomised to one of three groups: (1) exercise in a contextually enhanced environment, (2) exercise in a standard environment and (3) waiting list. The contextually enhanced environment is located in a newly built facility, has large windows providing abundant daylight and overlooks a recreational park. The standard environment is in a basement, has artificial lighting and is marked by years of use; that is, resembling many clinical environments. The primary outcome is the participant's global perceived effect rated on a seven-point Likert scale after 8 weeks exercise. Patient-reported and objective secondary outcomes are included. Ethics and dissemination The Regional Scientific Ethical Committee for Southern Denmark has approved the study. Study findings will be disseminated in peer-reviewed publications and presented at national and international conferences. Trial registration number NCT02043613. PMID:25818278

  4. Case Report: Stevens-Johnson syndrome following a single double dosing of nevirapine-containing regimen once in an HIV-infected woman on long-term antiretroviral therapy.

    PubMed Central

    Kakande, Betty; Isaacs, Thuraya; Muloiwa, Rudzani; Dlamini, Sipho; Lehloenya, Rannakoe

    2015-01-01

    A 31-year old HIV-infected African woman on nevirapine, tenofovir and lamivudine for more than 4 years presented with an 8-day history of symptoms and signs of Stevens-Johnson syndrome. She was on no other medication. Her viral load was undetectable and she had maintained a CD4 count of between 356 and 387cells/mm 3 in the preceding 2½ years. She missed her antiretrovirals 10 days before the onset of her symptoms and subsequently doubled her daily dose the following day. She had been on no other medication in the preceding 8 weeks. Her ARVs were stopped and she fully re-epithelialized with the exception of the lips, over the following 10 days. She was started on a daily single tablet of Odimune® (a fixed drug combination antiretroviral containing tenofovir, emtricitabine and efavirenz). Nevirapine is the most common offender in cases of antiretroviral-associated SJS in published literature. Lamivudine is very rarely implicated while there are no similar reports with tenofovir.  We concluded that nevirapine was by far the most likely offender in this case. Nevirapine toxicity is associated with high CD4 counts, undetectable viral load and high drug plasma level. We postulate that the sudden increase of the plasma levels of nevirapine in a patient with a high CD4 count and undetectable viral load created a perfect storm for the development of SJS in our patient, who had been on the NVP-containing regimen for many years. Clinicians should be aware that severe adverse drug reactions are dynamic and can occur even when the drug has been in use for a long time. PMID:26629333

  5. A Randomized, Double-blind Evaluation of D-cycloserine or Alprazolam Combined with Virtual Reality Exposure Therapy for Posttraumatic Stress Disorder (PTSD) in Iraq and Afghanistan War Veterans

    PubMed Central

    Rothbaum, Barbara Olasov; Price, Matthew; Jovanovic, Tanja; Norrholm, Seth D.; Gerardi, Maryrose; Dunlop, Boadie; Davis, Michael; Bradley, Bekh; Duncan, Erica; Rizzo, Albert “Skip”; Ressler, Kerry J.

    2014-01-01

    Objective To determine the effectiveness of Virtual Reality Exposure (VRE) augmented with D-cycloserine (50mg) or alprazolam (0.25mg), compared to placebo, in reducing PTSD due to military trauma in Iraq and Afghanistan. Method A double-blind, placebo-controlled randomized clinical trial comparing augmentation methods for VRE for subjects (n= 156) with PTSD was conducted. Results PTSD symptoms significantly improved from pre- to post-treatment over the 6-session VRE treatment (p<.001) across all conditions and were maintained at 3, 6, and 12 months follow-up. There were no overall differences between the D-cycloserine group on symptoms at any time-point. The alprazolam and placebo conditions significantly differed on the post-treatment Clinician Administered PTSD scale (p = .006) and the 3-month post-treatment PTSD diagnosis, such that the alprazolam group showed greater rates of PTSD (79.2% alprazolam vs. 47.8% placebo). Between-session extinction learning was a treatment-specific enhancer of outcome for the D-cycloserine group only (p<.005). At post-treatment, the D-cycloserine group was the lowest on cortisol reactivity (p<.05) and startle response during VR scenes (p<.05). Conclusions A small number of VRE sessions were associated with reduced PTSD diagnosis and symptoms in Iraq/Afghanistan veterans, although there was no control condition for the VRE. Overall, there was no advantage of D-cycloserine on PTSD symptoms in primary analyses. In secondary analyses, benzodiazepine use during treatment may impair recovery, and D-cycloserine may enhance VRE in patients who demonstrate within-session learning. D-cycloserine augmentation treatment in PTSD patients may reduce cortisol and startle reactivity compared to the alprazolam and placebo treatment, consistent with the animal literature. PMID:24743802

  6. Photodynamic topical antimicrobial therapy for infected foot ulcers in patients with diabetes: a randomized, double-blind, placebo-controlled study--the D.A.N.T.E (Diabetic ulcer Antimicrobial New Topical treatment Evaluation) study.

    PubMed

    Mannucci, Edoardo; Genovese, Stefano; Monami, Matteo; Navalesi, Giovanni; Dotta, Francesco; Anichini, Roberto; Romagnoli, Fabio; Gensini, Gianfranco

    2014-01-01

    This study was designed to assess the antimicrobial effect and tolerability of a single dose of a photo-activated gel containing RLP068 in the treatment for infected foot ulcers in subjects with diabetes. A randomized, double-blind, parallel series, placebo-controlled phase IIa trial was performed with three concentrations of RLP068 (0.10, 0.30, and 0.50 %), measuring total and pathogen microbial load on Day 1 (before and 1 h after topical gel application and photoactivation with 689 nm red light), on Days 3, 8, and 15, as add-on to systemic treatment with amoxicillin and clavulanic acid. Blood samples were also drawn 1, 2, and 48 h after administration for the assessment of systemic drug absorption. The trial was performed on 62 patients aged ≥18 years, with type 1 or type 2 diabetes and infected foot ulcer, with an area of 2-15 cm(2) and a maximum diameter ≤4.6 cm. A dose-dependent reduction in total microbial load was observed (-1.92 ± 1.21, -2.94 ± 1.60, and -3.00 ± 1.82 LogCFU/ml for 0.10, 0.30, and 0.50 % RPL068 vs. -1.00 ± 1.02 LogCFU/ml with placebo) immediately after illumination, with a progressive fading of the effect during follow-up. No safety issues emerged from the analysis of adverse events. Systemic absorption of RLP068 was negligible. Photodynamic antimicrobial treatment with RLP068 of infected diabetic foot ulcers is well tolerated and produces a significant reduction in germ load. Further clinical trials are needed to verify the efficacy of this approach as add-on to systemic antibiotic treatment. PMID:24352342

  7. Does Zinc Sulfate Prevent Therapy-Induced Taste Alterations in Head and Neck Cancer Patients? Results of Phase III Double-Blind, Placebo-Controlled Trial from the North Central Cancer Treatment Group (N01C4)

    SciTech Connect

    Halyard, Michele Y.; Jatoi, Aminah . E-mail: Jatoi.aminah@mayo.edu; Sloan, Jeff A.; Bearden, James D.; Vora, Sujay A.; Atherton, Pamela J.; Perez, Edith A.; Soori, Gammi; Zalduendo, Anthony C.; Zhu, Angela; Stella, Philip J.; Loprinzi, Charles L.

    2007-04-01

    Purpose: Taste alterations (dysgeusia) are well described in head and neck cancer patients who undergo radiotherapy (RT). Anecdotal observations and pilot studies have suggested zinc may mitigate these symptoms. This multi-institutional, double-blind, placebo-controlled trial was conducted to provide definitive evidence of this mineral's palliative efficacy. Methods and Materials: A total of 169 evaluable patients were randomly assigned to zinc sulfate 45 mg orally three times daily vs. placebo. Treatment was to be given throughout RT and for 1 month after. All patients were scheduled to receive {>=}2,000 cGy of external beam RT to {>=}30% of the oral cavity, were able to take oral medication, and had no oral thrush at study entry. Changes in taste were assessed using the previously validated Wickham questionnaire. Results: At baseline, the groups were comparable in age, gender, and planned radiation dose (<6,000 vs. {>=}6,000 cGy). Overall, 61 zinc-treated (73%) and 71 placebo-exposed (84%) patients described taste alterations during the first 2 months (p = 0.16). The median interval to taste alterations was 2.3 vs. 1.6 weeks in the zinc-treated and placebo-exposed patients, respectively (p = 0.09). The reported taste alterations included the absence of any taste (16%), bitter taste (8%), salty taste (5%), sour taste (4%), sweet taste (5%), and the presence of a metallic taste (10%), as well as other descriptions provided by a write in response (81%). Zinc sulfate did not favorably affect the interval to taste recovery. Conclusion: Zinc sulfate, as prescribed in this trial, did not prevent taste alterations in cancer patients who were undergoing RT to the oral pharynx.

  8. Soft-tissue injuries from sports activities and traffic accidents--treatment with low-level laser therapy: a multicenter double-blind placebo-controlled clinical study on 132 patients

    NASA Astrophysics Data System (ADS)

    Simunovic, Zlatko; Trobonjaca, Tatjana

    2000-06-01

    The aim of current multicenter clinical study was to assess the efficacy of low energy-level laser therapy (LLLT) in the treatment of soft tissue injuries compared to the placebo and classical phyiotherapeutic procedures. This clinical study was conducted in two centers located in Locarno, Switzerland and Opatija, Croatia. Two types of irradiation techniques were used: (1) direct, skin contact technique for treatment of trigger points where IR diode laser 830 nm continuous wave was applied; and (2) scanning technique for irradiation of larger surface area with use of Helium Neon laser 632.8 nm combined with IR diode laser 904 nm pulsed wave. Results were evaluated according to clinical parameters like: hematoma, swelling, heat, pan and loss of function. The findings were statistically analyzed via chi- square test. Results have demonstrated that the recovery process was accelerated in 85 percent of patients treated with LLLT compared to the control group of patients. The results and advantages obtained proved once again the efficacy of LLLT as a new and successful way to treat soft tissue injuries.

  9. Radiation therapy

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/001918.htm Radiation therapy To use the sharing features on this page, please enable JavaScript. Radiation therapy uses high-powered x-rays, particles, or ...

  10. Alternative Therapies

    MedlinePlus

    ... Late Effects of Poliomyelitis for Physicians and Survivors © Alternative Therapies Alternative therapies, also called complementary, can support ... of motion, pain, and fatigue are often reported. Energy work includes acupuncture and acupressure, traditional Chinese medicine ...

  11. Radiation Therapy

    MedlinePlus

    Radiation therapy is a cancer treatment. It uses high doses of radiation to kill cancer cells and stop them ... places inside your body. The type of radiation therapy you receive depends on many factors, including The ...

  12. Radiation Therapy

    MedlinePlus

    ... people who have radiation therapy may feel more tired than usual, not feel hungry, or lose their ... of radiation therapy include: Fatigue. Fatigue, or feeling tired, is the most common side effect of radiation ...

  13. Dynamics of Double Stochastic Operators

    NASA Astrophysics Data System (ADS)

    Saburov, Mansoor

    2016-03-01

    A double stochastic operator is a generalization of a double stochastic matrix. In this paper, we study the dynamics of double stochastic operators. We give a criterion for a regularity of a double stochastic operator in terms of absences of its periodic points. We provide some examples to insure that, in general, a trajectory of a double stochastic operator may converge to any interior point of the simplex.

  14. Double Emulsion Templated Celloidosomes

    NASA Astrophysics Data System (ADS)

    Arriaga, Laura R.; Marquez, Samantha M.; Kim, Shin-Hyun; Chang, Connie; Wilking, Jim; Monroy, Francisco; Marquez, Manuel; Weitz, David A.

    2012-02-01

    We present a novel approach for fabricating celloidosomes, which represent a hollow and spherical three-dimensional self-assembly of living cells encapsulating an aqueous core. Glass- capillary microfluidics is used to generate monodisperse water-in-oil-in-water double emulsion templates using lipids as stabilizers. Such templates allow for obtaining single but also double concentric celloidosomes. In addition, after a solvent removal step the double emulsion templates turn into monodisperse lipid vesicles, whose membrane spontaneously phase separates when choosing the adequate lipid composition, providing the adequate scaffold for fabricating Janus-celloidosomes. These structures may find applications in the development of bioreactors in which the synergistic effects of two different types of cells selectively adsorbed on one of the vesicle hemispheres may be exploited.

  15. Tracking The Double Eagle

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Last summer a trio of aeronauts made aviation history. Ben Abruzzo, Maxie Anderson and Larry Newman, all of Albuquerque, New Mexico, piloted their balloon Double Eagle I1 from Presque Isle, Maine to Miserey, France, some 50 miles from Paris. They were the first to negotiate a successful Atlantic crossing in a freeflying balloon after a score of attempts over a span of more than a century. A year earlier, Abruzzo and Anderson had made an unsuccessful try in their predecessor balloon Double Eagle. On that occasion, a NASA-developed satellite beacon helped save their lives. Carried aboard the balloon, the simple, seven-pound beacon continuously transmitted signals to NASA's Nimbus-6 satellite. Nimbus relayed the signals to monitors at Goddard Space Flight Center, enabling Goddard to compute the balloon's position. Position reports were then telephoned regularly to Double Eagle's control center at Bedford, Massachusetts. This monitoring system proved invaluable when the balloon encountered trouble several days after liftoff.

  16. Double face sealing device

    NASA Technical Reports Server (NTRS)

    Weddendorf, Bruce C. (Inventor)

    1991-01-01

    A double face sealing device for mounting between two surfaces to provide an airtight and fluid-tight seal between a closure member bearing one of the surfaces and a structure or housing bearing the other surface which extends around the opening or hatchway to be closed. The double face sealing device includes a plurality of sections or segments mounted to one of the surfaces, each having a main body portion, a pair of outwardly extending and diverging, cantilever, spring arms, and a pair of inwardly extending and diverging, cantilever, spring arms, an elastomeric cover on the distal, free, ends of the outwardly extending and diverging spring arms, and an elastomeric cover on the distal, free, ends of the inwardly extending and diverging spring arms. The double face sealing device has application or use in all environments requiring a seal, but is particularly useful to seal openings or hatchways between compartments of spacecraft or aircraft.

  17. Feminist Therapy.

    ERIC Educational Resources Information Center

    Laidlaw, Toni; Malmo, Cheryl

    1991-01-01

    Traces roots of feminist therapy and its independence from traditional and prevalent theories and therapy practices. Asserts that Freudian theory and humanistic assumptions are sexist and contribute to powerlessness of women. In contrast, feminist therapy is seen as dealing directly with client-counselor relationships, trust, advocacy, and…

  18. Efficacy, tolerability, and safety of aripiprazole once-monthly versus other long-acting injectable antipsychotic therapies in the maintenance treatment of schizophrenia: a mixed treatment comparison of double-blind randomized clinical trials

    PubMed Central

    Majer, Istvan M.; Gaughran, Fiona; Sapin, Christophe; Beillat, Maud; Treur, Maarten

    2015-01-01

    Background Treatment with long-acting injectable (LAI) antipsychotic medication is an important element of relapse prevention in schizophrenia. Recently, the intramuscular once-monthly formulation of aripiprazole received marketing approval in Europe and the United States for schizophrenia. Objective This study aimed to compare aripiprazole once-monthly with other LAI antipsychotics in terms of efficacy, tolerability, and safety. Data sources A systematic literature review was conducted to identify relevant double-blind randomized clinical trials of LAIs conducted in the maintenance treatment of schizophrenia. MEDLINE, MEDLINE In-Process, Embase, the Cochrane Library, PsycINFO, conference proceedings, clinical trial registries, and the reference lists of key review articles were searched. The literature search covered studies dating from January 2002 to May 2013. Study selection Studies were required to have ≥24 weeks of follow-up. Patients had to be stable at randomization. Studies were not eligible for inclusion if efficacy of acute and maintenance phase treatment was not reported separately. Six trials were identified (0.5% of initially identified studies), allowing comparisons of aripiprazole once-monthly, risperidone LAI, paliperidone palmitate, olanzapine pamoate, haloperidol depot, and placebo. Data extraction Data extracted included study details, study duration, the total number of patients in each treatment arm, efficacy, tolerability, and safety outcomes. The efficacy outcome contained the number of patients that experienced a relapse, tolerability outcomes included the number of patients that discontinued treatment due to treatment-related adverse events (AEs), and that discontinued treatment due to reasons other than AEs (e.g., loss to follow-up). Safety outcomes included the incidence of clinically relevant weight gain and extrapyramidal symptoms. Data synthesis Data were analyzed by applying a mixed treatment comparison competing risks model

  19. Feasibility, double-blind, randomised, placebo-controlled, multi-centre trial of hand-held NB-UVB phototherapy for the treatment of vitiligo at home (HI-Light trial: Home Intervention of Light therapy)

    PubMed Central

    2014-01-01

    Background Hand-held NB-UVB units are lightweight devices that may overcome the need to treat vitiligo in hospital-based phototherapy cabinets, allowing early treatment at home that may enhance the likelihood of successful repigmentation. The pilot Hi-Light trial examined the feasibility of conducting a large multi-centre randomised controlled trial (RCT) on the use of such devices by exploring recruitment, adherence, acceptability, and patient education. Methods This was a feasibility, double-blind, multi-centre, parallel group randomised placebo-controlled trial of hand-held NB-UVB phototherapy for the treatment of vitiligo at home. The overall duration of the trial was seven months; three months recruitment and four months treatment. Participants were randomly allocated to active or placebo groups (2:1 ratio). The primary outcome measure was the proportion of eligible participants who were willing to be randomised. The secondary outcomes included proportion of participants expressing interest in the trial and fulfilling eligibility criteria, withdrawal rates and missing data, proportion of participants adhering to and satisfied with the treatment, and incidence of NB-UVB short-term adverse events. Results Eighty-three percent (45/54) of vitiligo patients who expressed interest in the trial were willing to be randomised. Due to time and financial constraints, only 29/45 potential participants were booked to attend a baseline hospital visit. All 29 (100%) potential participants were confirmed as being eligible and were subsequently randomised. Willingness to participate in the study for General Practice (family physicians) surgeries and hospitals were 40% and 79%, respectively; 86% (25/29) of patients adhered to the treatment and 65% (7/11) of patients in the active group had some degree of repigmentation. Only one patient in the active group reported erythema grade 3 (3%). Both devices (Dermfix 1000 NB-UVB and Waldmann NB-UVB 109) were acceptable to participants

  20. Design friendly double patterning

    NASA Astrophysics Data System (ADS)

    Yesilada, Emek

    2012-03-01

    Double patterning using 193nm immersion has been adapted as the solution to enable 2x nm technology nodes until the arrival of EUV tools. As a result the past few years have seen a huge effort in creating double patterning friendly design flows. These flows have so far proposed a combination of decomposition rules at cell level and/or at placement level as well as sophisticated decomposition tools with varying density, design iteration and decomposition complexity penalties. What is more, designers have to familiarize themselves with double patterning challenges and decomposition tools. In this paper an alternative approach is presented that allows the development of dense standard cells with minimal impact on design flow due to double patterning. A real case study is done on 20nm node first metal layer where standard cells are designed without considering decomposition restrictions. The resulting layout is carefully studied in order to establish decomposition or color rules that can map the layout into two masks required for double patterning but without the need of complex coloring algorithms. Since the rules are derived from a decomposition unaware design they do not in return impose heavy restrictions on the design at the cell or placement level and show substantial density gains compared to previously proposed methods. Other key advantages are a simplified design flow without complex decomposition tools that can generate a faster time to market solution all at the same time keeping designers isolated from the challenges of the double patterning. The derived design rules highlight process development path required for design driven manufacturing.

  1. Double Bragg Interferometry.

    PubMed

    Ahlers, H; Müntinga, H; Wenzlawski, A; Krutzik, M; Tackmann, G; Abend, S; Gaaloul, N; Giese, E; Roura, A; Kuhl, R; Lämmerzahl, C; Peters, A; Windpassinger, P; Sengstock, K; Schleich, W P; Ertmer, W; Rasel, E M

    2016-04-29

    We employ light-induced double Bragg diffraction of delta-kick collimated Bose-Einstein condensates to create three symmetric Mach-Zehnder interferometers. They rely on (i) first-order, (ii) two successive first-order, and (iii) second-order processes which demonstrate the scalability of the corresponding momentum transfer. With respect to devices based on conventional Bragg scattering, these symmetric interferometers double the scale factor and feature a better suppression of noise and systematic uncertainties intrinsic to the diffraction process. Moreover, we utilize these interferometers as tiltmeters for monitoring their inclination with respect to gravity. PMID:27176520

  2. Double Bragg Interferometry

    NASA Astrophysics Data System (ADS)

    Ahlers, H.; Müntinga, H.; Wenzlawski, A.; Krutzik, M.; Tackmann, G.; Abend, S.; Gaaloul, N.; Giese, E.; Roura, A.; Kuhl, R.; Lämmerzahl, C.; Peters, A.; Windpassinger, P.; Sengstock, K.; Schleich, W. P.; Ertmer, W.; Rasel, E. M.

    2016-04-01

    We employ light-induced double Bragg diffraction of delta-kick collimated Bose-Einstein condensates to create three symmetric Mach-Zehnder interferometers. They rely on (i) first-order, (ii) two successive first-order, and (iii) second-order processes which demonstrate the scalability of the corresponding momentum transfer. With respect to devices based on conventional Bragg scattering, these symmetric interferometers double the scale factor and feature a better suppression of noise and systematic uncertainties intrinsic to the diffraction process. Moreover, we utilize these interferometers as tiltmeters for monitoring their inclination with respect to gravity.

  3. Double-helix stellarator

    SciTech Connect

    Moroz, P.E.

    1997-09-01

    A new stellarator configuration, the Double-Helix Stellarator (DHS), is introduced. This novel configuration features a double-helix center post as the only helical element of the stellarator coil system. The DHS configuration has many unique characteristics. One of them is the extreme low plasma aspect ratio, A {approx} 1--1.2. Other advantages include a high enclosed volume, appreciable rotational transform, and a possibility of extreme-high-{beta} MHD equilibria. Moreover, the DHS features improved transport characteristics caused by the absence of the magnetic field ripple on the outboard of the torus. Compactness, simplicity and modularity of the coil system add to the DHS advantages for fusion applications.

  4. Double arch mirror study

    NASA Technical Reports Server (NTRS)

    Vukobratovich, D.; Hillman, D.

    1983-01-01

    The development of a method of mounting light weight glass mirrors for astronomical telescopes compatible with the goals of the Shuttle Infrared Telescope Facility (SIRTF) was investigated. A 20 in. diameter double arch lightweight mirror previously fabricated was modified to use a new mount configuration. This mount concept was developed and fabricated. The mounting concept of the double mounting mirror is outlined. The modifications made to the mirror, fabrication of the mirror mount, and room temperature testing of the mirror and mount and the extension of the mirror and mount concept to a full size (40 in. diameter) primary mirror for SIRTF are discussed.

  5. ULTIMATE-SHF trial (UdenafiL Therapy to Improve symptoMAtology, exercise Tolerance and hEmodynamics in patients with chronic systolic heart failure): study protocol for a randomized, placebo-controlled, double-blind trial

    PubMed Central

    2013-01-01

    Background Over the last few years, the use of phosphodiesterase type 5 (PDE5) inhibitors has been expanded to management of various cardiovascular disorders beyond pulmonary arterial hypertension. This study is designed to investigate the ability of udenafil, a newly developed long-acting PDE5 inhibitor, to improve functional capacity and hemodynamic status in a cohort of chronic systolic heart failure (SHF) patients. Methods/design Stable, chronic SHF patients will be randomly assigned to placebo (26 patients) or udenafil at a dose of 50 mg twice per day (26 patients) for the first 4 weeks followed by 100 mg twice daily for the next 8 weeks. Eligibility criteria will be age ≥18 years, clinical diagnosis of chronic SHF with current New York Heart Association class II to IV symptoms, left ventricular ejection fraction ≤ 40%, and experience of at least one of following during the 12 months prior to study entry: hospitalization for decompensated heart failure, acute treatment with intravenous loop diuretics or hemofiltration, or pulmonary artery systolic pressure ≥40mmHg on transthoracic echocardiography. Pharmacological therapy for SHF will be optimized in all patients at least 30 days before study entry. The primary outcome will be the change of maximal oxygen uptake, assessed by cardiopulmonary exercise testing. Secondary outcomes will include changes in ventilatory efficiency (minute ventilation/carbon dioxide production slope), left ventricular systolic and diastolic parameters, pulmonary artery systolic pressure, plasma concentration of brain natriuretic peptide, occurrence of mortality or hospitalization for heart failure, and the occurrence of any adverse event. Clinical trial registration Unique identifier: NCT01646515 PMID:23799908

  6. Double-Glazing Interferometry

    ERIC Educational Resources Information Center

    Toal, Vincent; Mihaylova, Emilia M.

    2009-01-01

    This note describes how white light interference fringes can be seen by observing the Moon through a double-glazed window. White light interferometric fringes are normally observed only in a well-aligned interferometer whose optical path difference is less than the coherence length of the light source, which is approximately one micrometer for…

  7. Rosette (Double Blossom)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rosette, or double blossom, is a serious disease of erect blackberries that is limited to the genus Rubus. Rosette may occur on trailing blackberries and dewberries, but rarely on red and black raspberries. In the United States, rosette occurs from New Jersey to Illinois and southwest to Texas and i...

  8. Double layers without current

    SciTech Connect

    Perkins, F.W.; Sun, Y.C.

    1980-11-01

    The steady-state solution of the nonlinear Vlasov-Poisson equations is reduced to a nonlinear eigenvalue problem for the case of double-layer (potential drop) boundary conditions. Solutions with no relative electron-ion drifts are found. The kinetic stability is discussed. Suggestions for creating these states in experiments and computer simulations are offered.

  9. Double resonator cantilever accelerometer

    DOEpatents

    Koehler, Dale R.

    1984-01-01

    A digital quartz accelerometer includes a pair of spaced double-ended tuning forks fastened at one end to a base and at the other end through a spacer mass. Transverse movement of the resonator members stresses one and compresses the other, providing a differential frequency output which is indicative of acceleration.

  10. Double resonator cantilever accelerometer

    DOEpatents

    Koehler, D.R.

    1982-09-23

    A digital quartz accelerometer includes a pair of spaced double-ended tuning forks fastened at one end to a base and at the other end through a spacer mass. Transverse movement of the resonator members stresses one and compresses the other, providing a differential frequency output which is indicative of acceleration.

  11. Double Trouble (Abstract)

    NASA Astrophysics Data System (ADS)

    Simonsen, M.

    2015-12-01

    (Abstract only) Variable stars with close companions can be difficult to accurately measure and characterize. The companions can create misidentifications, which in turn can affect the perceived magnitudes, amplitudes, periods, and colors of the variable stars. We will show examples of these Double Trouble stars and the impact their close companions have had on our understanding of some of these variable stars.

  12. Weathering the Double Whammy.

    ERIC Educational Resources Information Center

    Wellman, Jane V.

    2002-01-01

    Discusses how governing boards can help their institutions weather the "double-whammy" of doing more with less: identify the institution's short-term and long-term challenges; refocus the institution's mission, planning, and programming; assess and integrate the institution's tuition, aid, and outreach strategies; redouble the institution's…

  13. Sun Packs Double Punch

    NASA Video Gallery

    On August 3, the sun packed a double punch, emitting a M6.0-class flare at 9:43 am EDT. This video is of the second, slightly stronger M9.3-class flare at 11:41 pm EDT. Both flares had significant ...

  14. Double-Entry Bookkeeping.

    ERIC Educational Resources Information Center

    Snyder, Herbert

    1999-01-01

    Explains the principles and mechanics of double-entry bookkeeping as a part of the accounting cycle to produce a functioning set of accounting records. Suggests that libraries need to have accurate and timely information about their spending to gain financial control and protect against fraud and abuse. (LRW)

  15. A matterless double slit

    NASA Astrophysics Data System (ADS)

    King, Ben; di Piazza, Antonino; Keitel, Christoph H.

    2010-02-01

    Double slits provide incoming particles with a choice. Those that survive passage through the slits have chosen from two possible paths, which interfere to distribute them in a wave-like manner. Such wave-particle duality continues to be challenged and investigated in a broad range of disciplines with electrons, neutrons, helium atoms, C60 fullerenes, Bose-Einstein condensates and biological molecules. All variants have hitherto involved material constituents. We present a matterless double-slit scenario in which photons generated from virtual electron-positron pair annihilation in head-on collisions of a probe laser field with two ultra-intense laser beams form a double-slit interference pattern. Such electromagnetic fields are predicted to induce material-like behaviour in vacuum, supporting elastic scattering between photons. Our double-slit scenario presents, on the one hand, a realizable method with which to observe photon-photon scattering and, on the other hand, demonstrates the possibility of both controlling light with light and non-locally investigating features of the quantum vacuum structure.

  16. Double Marking Revisited

    ERIC Educational Resources Information Center

    Brooks, Val

    2004-01-01

    In 2002, the Qualifications and Curriculum Authority (QCA) published the report of an independent panel of experts into maintaining standards at Advanced Level (A-Level). One of its recommendations was for: limited experimental double marking of scripts in subjects such as English to determine whether the strategy would significantly reduce errors…

  17. [Double ricochet marks].

    PubMed

    Sellier, K

    1987-01-01

    When bullets are flying stably and ricochet on a surface, only one mark is produced. In contrast yawing bullets can produce a double mark if the angle of incidence is sufficiently small (less than or equal to 5 degrees). Distances up to 15 cm were seen between the two marks. PMID:3660953

  18. Teaching the Double Layer.

    ERIC Educational Resources Information Center

    Bockris, J. O'M.

    1983-01-01

    Suggests various methods for teaching the double layer in electrochemistry courses. Topics addressed include measuring change in absolute potential difference (PD) at interphase, conventional electrode potential scale, analyzing absolute PD, metal-metal and overlap electron PDs, accumulation of material at interphase, thermodynamics of electrified…

  19. Design for Double Rainbow

    ERIC Educational Resources Information Center

    Thomas, Lisa Carlucci

    2011-01-01

    Rare is the inspirational, spontaneous, transformative moment shared among 20 million people. In the summer of 2010, people around the world were moved by the sighting of a double rainbow--almost a triple rainbow--"all the way across the sky" in Yosemite National Park. Caught on video and posted to by YouTube by Paul Vasquez in January 2010, the…

  20. Relation Between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Study.

    PubMed

    Giustino, Gennaro; Kirtane, Ajay J; Généreux, Philippe; Baber, Usman; Witzenbichler, Bernhard; Neumann, Franz-Josef; Weisz, Giora; Maehara, Akiko; Rinaldi, Michael J; Metzger, Christopher; Henry, Timothy D; Cox, David A; Duffy, Peter L; Mazzaferri, Ernest L; Brodie, Bruce R; Stuckey, Thomas D; Dangas, George D; Francese, Dominic P; Litherland, Claire; Mehran, Roxana; Stone, Gregg W

    2016-06-01

    Whether the association between platelet count (PC) and thrombotic and bleeding risk is independent of or varies by residual platelet reactivity to antiplatelet therapies is unclear. We sought to investigate the independent and combined effects of PC and platelet reactivity on thrombotic and bleeding risk after coronary artery implantation of drug-eluting stents (DES). Patients enrolled in the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents study were stratified by PC tertiles. The study cohort comprised 8,402 patients. By linear regression analysis, lower PC was strongly and independently associated with higher platelet reactive units (PRUs) on clopidogrel. After multivariable adjustment (including PRU and aspirin reactive units), high, but not low, PC tertile was independently associated with higher risk of thrombotic complications, including spontaneous myocardial infarction and stent thrombosis. Although no independent association was observed between PC tertiles and hemorrhagic risk, both high and low PC tertiles were associated with increased risk for all-cause mortality. After stratification of PC tertiles by tertiles of PRUs, the crude risk of thrombotic complications was highest in patients in the high PC and high PRU tertiles. By multivariable adjustment, PRU increases were uniformly associated with higher risk of thrombotic events across PC tertiles, without evidence of interaction. In conclusion, higher PCs and higher PRUs act independently and synergistically in determining thrombotic risk. Alongside PRU, PCs could be a simple hematological parameter to consider for risk stratification and in tailoring duration and potency of pharmacologic platelet inhibition after DES implantation. PMID:27067621

  1. Double Degrees: Double the Trouble or Twice the Return?

    ERIC Educational Resources Information Center

    Russell, A. Wendy; Dolnicar, Sara; Ayoub, Marina

    2008-01-01

    Double degrees (also called joint or combined degrees)--programs of study combining two bachelor degrees--are increasingly popular in Australian universities, particularly among women. A case study using qualitative and quantitative surveys of current and past double degree students is presented. The study indicates that double degrees benefit…

  2. Effective desynchronization by means of double-pulse phase resetting

    NASA Astrophysics Data System (ADS)

    Tass, P. A.

    2001-01-01

    A double-pulse stimulation technique is presented here for the first time which makes it possible to effectively desynchronize a synchronized cluster of globally coupled phase oscillators in the presence of noise. The first, stronger pulse of the double pulse restarts the cluster independently of its initial dynamic state. The second, weaker pulse desynchronizes the cluster by hitting it in a vulnerable state. After the desynchronization the cluster tends to resynchronize since the incoherent state is unstable. Nevertheless, repeated administration of double pulses blocks the cluster's resynchronization. This approach can directly be applied to real data. Accordingly, a demand-controlled deep-brain double-pulse stimulation technique is suggested for the therapy of patients suffering from Parkinson's disease or essential tremor.

  3. Tests on Double Layer Metalization

    NASA Technical Reports Server (NTRS)

    Woo, D. S.

    1983-01-01

    28 page report describes experiments in fabrication of integrated circuits with double-layer metalization. Double-layer metalization requires much less silicon "real estate" and allows more flexibility in placement of circuit elements than does single-layer metalization.

  4. Measuring the Double Helix

    SciTech Connect

    Mathew-Fenn, R.S.; Das, R.; Harbury, P.A.B.

    2009-05-26

    DNA is thought to behave as a stiff elastic rod with respect to the ubiquitous mechanical deformations inherent to its biology. To test this model at short DNA lengths, we measured the mean and variance of end-to-end length for a series of DNA double helices in solution, using small-angle x-ray scattering interference between gold nanocrystal labels. In the absence of applied tension, DNA is at least one order of magnitude softer than measured by single-molecule stretching experiments. Further, the data rule out the conventional elastic rod model. The variance in end-to-end length follows a quadratic dependence on the number of base pairs rather than the expected linear dependence, indicating that DNA stretching is cooperative over more than two turns of the DNA double helix. Our observations support the idea of long-range allosteric communication through DNA structure.

  5. Double meningocele. Case report.

    PubMed

    Durmaz, R; Arslantaş, A; Ozön, Y H; Tel, E

    2000-01-01

    The coexistence of two distinct meningoceles of the spine is a very unusual event. We report a three-day-old boy with double meningoceles at the thoracic and lumbar levels. The connection between the stalk of the thoracic meningocele and the spinal cord, as seen on magnetic resonance imaging, showed a neurological involvement in this lesion. Our case is only the third without association of congenital anomalies or neurofibromatosis to be reported to date. PMID:11196754

  6. The double massa intermedia

    PubMed Central

    Baydin, Serhat; Gungor, Abuzer; Baran, Oguz; Tanriover, Necmettin; Rhoton, Albert L.

    2016-01-01

    Background: To describe the rare finding of a double massa intermedia (MI). Typically, the MI (interthalamic adhesion) is a single bridge of gray matter connecting the medial surfaces of the thalami. Methods: Twelve formalin- and alcohol-fixed human third ventricles were examined from superior to inferior by fiber dissection technique under ×6 to ×40 magnifications and with the endoscope. Results: In all hemispheres, the anterior and posterior commissure were defined. The MI, which bridges the medial surfaces of the thalami, was defined in all hemispheres. In one hemisphere, there was a second bridge between the thalami, located posteroinferior to the common MI. Endoscopic view confirmed that there was a second MI in this specimen. The MI usually traverses the third ventricle posterior to the foramen of Monro and connects the paired thalami. The MI is an important landmark during endoscopic and microscopic surgeries of the third ventricle. Although a double MI is very rare, surgeons should be aware of the possibility in their surgical planning. Conclusion: The surgeon should be aware of the possibility of a double MI to avoid confusion during third ventricle surgery. PMID:27127695

  7. Double face sealing device

    NASA Technical Reports Server (NTRS)

    Weddendorf, Bruce (Inventor)

    1991-01-01

    A double face sealing device is disclosed for mounting between two surfaces to provide an air-tight and fluid-tight seal between a closure member bearing one of the surfaces and a structure or housing bearing the other surface which extends around the opening or hatchway to be closed. The double face sealing device includes a plurality of sections or segments mounted to one of the surfaces, each having a main body portion, a pair of outwardly extending and diverging, cantilever, spring arms, and a pair of inwardly extending and diverging, cantilever, spring arms, an elastomeric cover on the distal, free ends of the outwardly extending and diverging spring arms, and an elastomeric cover on the distal, free, ends of the outwardly extending and diverging spring arms, and an elastomeric cover on the distal, free ends of the inwardly extending and diverging spring arms. The double face sealing device has application or use in all environments requiring a seal, but is particularly useful to seal openings or hatchways between compartments of spacecraft or aircraft.

  8. Colloidal Double Quantum Dots

    PubMed Central

    2016-01-01

    Conspectus Pairs of coupled quantum dots with controlled coupling between the two potential wells serve as an extremely rich system, exhibiting a plethora of optical phenomena that do not exist in each of the isolated constituent dots. Over the past decade, coupled quantum systems have been under extensive study in the context of epitaxially grown quantum dots (QDs), but only a handful of examples have been reported with colloidal QDs. This is mostly due to the difficulties in controllably growing nanoparticles that encapsulate within them two dots separated by an energetic barrier via colloidal synthesis methods. Recent advances in colloidal synthesis methods have enabled the first clear demonstrations of colloidal double quantum dots and allowed for the first exploratory studies into their optical properties. Nevertheless, colloidal double QDs can offer an extended level of structural manipulation that allows not only for a broader range of materials to be used as compared with epitaxially grown counterparts but also for more complex control over the coupling mechanisms and coupling strength between two spatially separated quantum dots. The photophysics of these nanostructures is governed by the balance between two coupling mechanisms. The first is via dipole–dipole interactions between the two constituent components, leading to energy transfer between them. The second is associated with overlap of excited carrier wave functions, leading to charge transfer and multicarrier interactions between the two components. The magnitude of the coupling between the two subcomponents is determined by the detailed potential landscape within the nanocrystals (NCs). One of the hallmarks of double QDs is the observation of dual-color emission from a single nanoparticle, which allows for detailed spectroscopy of their properties down to the single particle level. Furthermore, rational design of the two coupled subsystems enables one to tune the emission statistics from single

  9. Colloidal Double Quantum Dots.

    PubMed

    Teitelboim, Ayelet; Meir, Noga; Kazes, Miri; Oron, Dan

    2016-05-17

    Pairs of coupled quantum dots with controlled coupling between the two potential wells serve as an extremely rich system, exhibiting a plethora of optical phenomena that do not exist in each of the isolated constituent dots. Over the past decade, coupled quantum systems have been under extensive study in the context of epitaxially grown quantum dots (QDs), but only a handful of examples have been reported with colloidal QDs. This is mostly due to the difficulties in controllably growing nanoparticles that encapsulate within them two dots separated by an energetic barrier via colloidal synthesis methods. Recent advances in colloidal synthesis methods have enabled the first clear demonstrations of colloidal double quantum dots and allowed for the first exploratory studies into their optical properties. Nevertheless, colloidal double QDs can offer an extended level of structural manipulation that allows not only for a broader range of materials to be used as compared with epitaxially grown counterparts but also for more complex control over the coupling mechanisms and coupling strength between two spatially separated quantum dots. The photophysics of these nanostructures is governed by the balance between two coupling mechanisms. The first is via dipole-dipole interactions between the two constituent components, leading to energy transfer between them. The second is associated with overlap of excited carrier wave functions, leading to charge transfer and multicarrier interactions between the two components. The magnitude of the coupling between the two subcomponents is determined by the detailed potential landscape within the nanocrystals (NCs). One of the hallmarks of double QDs is the observation of dual-color emission from a single nanoparticle, which allows for detailed spectroscopy of their properties down to the single particle level. Furthermore, rational design of the two coupled subsystems enables one to tune the emission statistics from single photon

  10. Sweat Therapy.

    ERIC Educational Resources Information Center

    Colmant, Stephen A.; Merta, Rod J.

    2000-01-01

    A study combined group sweating and group counseling. Four adolescent boys with disruptive behavior disorders participated in 12 sweat therapy sessions. They reported the sessions useful for sharing personal concerns and receiving assistance with problem solving. Three boys showed improvement in self-esteem. Advantages of sweat therapy over other…

  11. Poetry Therapy.

    ERIC Educational Resources Information Center

    Evans, Ronald V.

    Poetry therapy is the method of therapy based on the principle that a poem is a special medium for expressing emotions and that this expression can have psychotherapeutic value. A survey taken in 1973 showed there were over 400 therapists treating 3,500 drug addicts, alcoholics, and mental retardates around the country. Poetry therapists…

  12. Intravenous Therapy.

    ERIC Educational Resources Information Center

    Galliart, Barbara

    Intended for teaching licensed practical nurses, this curriculum guide provides information related to the equipment and skills required for nursing care of patients needing intravenous (IV) therapy. It also explains the roles and responsibilities of the licensed practical nurse with regard to intravenous therapy. Each of the 15 instructional…

  13. Sex Therapy

    ERIC Educational Resources Information Center

    Hogan, Douglas

    1977-01-01

    Notes that no single theory of psychotherapy dominates the field of sex therapy. On one hand, sex therapy is not subject to the rigid dogmas of many areas of psychotherapy. But on the other hand, many techniques are invented at the whim of clinicians with no basis in theory. (Author/AM)

  14. Gene Therapy

    PubMed Central

    Baum, Bruce J

    2014-01-01

    Applications of gene therapy have been evaluated in virtually every oral tissue, and many of these have proved successful at least in animal models. While gene therapy will not be used routinely in the next decade, practitioners of oral medicine should be aware of the potential of this novel type of treatment that doubtless will benefit many patients with oral diseases. PMID:24372817

  15. Double pituitary adenomas.

    PubMed

    Iacovazzo, D; Bianchi, A; Lugli, F; Milardi, D; Giampietro, A; Lucci-Cordisco, E; Doglietto, F; Lauriola, L; De Marinis, L

    2013-04-01

    Double pituitary adenomas represent up to 2.6 % of pituitary adenomas in large surgical series and up to 3.3 % of patients with Cushing's disease have been found to have double or multiple pituitary adenomas. We report the case of a 60-year-old male patient whose medical history began in 2002 with erectile dysfunction; hyperprolactinemia was found and MRI showed a 6-mm area of delayed enhancement in the lateral portion of the right pituitary lobe. Treatment with cabergoline was started with normalization of prolactin levels; the following MRI, performed in 2005 and 2008, showed shrinkage of the pituitary lesion. In 2005, the patient began to manifest weight gain, hypertension, and facial plethora, but no further evaluations were done. In January 2010, the patient came to our attention and underwent multiple tests that suggested Cushing's disease. A new MRI was negative. Bilateral inferior petrosal sinus sampling showed significant pituitary-to-peripheral ratio and, in May 2010, the patient underwent exploratory pituitary surgery with evidence of a 1-2-mm white-coloured midline area compatible with pituitary adenoma that was surgically removed. Post-operatively, the patient's clinical conditions improved with onset of secondary hypoadrenalism. The histologic examination confirmed a pituitary adenoma (immunostaining was found to be positive for ACTH and negative for prolactin). We report the case of an ACTH-producing microadenoma metachronous to a prolactin secreting microadenoma although not confirmed histologically, shrunk by medical treatment. A review of data in the literature regarding double or multiple pituitary adenomas has also been done. PMID:23325364

  16. The Double Star mission

    NASA Astrophysics Data System (ADS)

    Liu, Z. X.; Escoubet, C. P.; Pu, Z.; Laakso, H.; Shi, J. K.; Shen, C.; Hapgood, M.

    2005-11-01

    The Double Star Programme (DSP) was first proposed by China in March, 1997 at the Fragrant Hill Workshop on Space Science, Beijing, organized by the Chinese Academy of Science. It is the first mission in collaboration between China and ESA. The mission is made of two spacecraft to investigate the magnetospheric global processes and their response to the interplanetary disturbances in conjunction with the Cluster mission. The first spacecraft, TC-1 (Tan Ce means "Explorer"), was launched on 29 December 2003, and the second one, TC-2, on 25 July 2004 on board two Chinese Long March 2C rockets. TC-1 was injected in an equatorial orbit of 570x79000 km altitude with a 28° inclination and TC-2 in a polar orbit of 560x38000 km altitude. The orbits have been designed to complement the Cluster mission by maximizing the time when both Cluster and Double Star are in the same scientific regions. The two missions allow simultaneous observations of the Earth magnetosphere from six points in space. To facilitate the comparison of data, half of the Double Star payload is made of spare or duplicates of the Cluster instruments; the other half is made of Chinese instruments. The science operations are coordinated by the Chinese DSP Scientific Operations Centre (DSOC) in Beijing and the European Payload Operations Service (EPOS) at RAL, UK. The spacecraft and ground segment operations are performed by the DSP Operations and Management Centre (DOMC) and DSOC in China, using three ground station, in Beijing, Shanghai and Villafranca.

  17. Antiparasitic Therapy

    PubMed Central

    Kappagoda, Shanthi; Singh, Upinder; Blackburn, Brian G.

    2011-01-01

    Parasitic diseases affect more than 2 billion people globally and cause substantial morbidity and mortality, particularly among the world's poorest people. This overview focuses on the treatment of the major protozoan and helminth infections in humans. Recent developments in antiparasitic therapy include the expansion of artemisinin-based therapies for malaria, new drugs for soil-transmitted helminths and intestinal protozoa, expansion of the indications for antiparasitic drug treatment in patients with Chagas disease, and the use of combination therapy for leishmaniasis and human African trypanosomiasis. PMID:21628620

  18. The Double Chooz Experiment

    NASA Astrophysics Data System (ADS)

    Pfahler, Patrick; Double Chooz Collaboration

    2012-07-01

    Double Chooz is a reactor bar nue-disappearance experiment situated at the commercial nuclear power plant of Chooz in northern France. The experiment aims for the revelation of the last unknown mixing angle Θ13 as a part of the neutrino mixing matrix or the improvement of the upper limit for sin2(2Θ13), which is currently < 0.14 (90% CL). A newly developed gadolinium-loaded liquid scintillator as target allows the detection of electron-anti-neutrinos (bar nue) using the inverse beta decay and its distinct decay pattern (bar nue + p → e+ +n). Double Chooz uses two identical detectors at different distances in order to reduce systematic uncertainties. This will allow, after a data taking phase of 4 years, an improvement on sin2(2Θ13) down to < 0.03 (90% CL). The first (far) detector has successfully been installed and filled, and takes data since April of 2011. A preliminary analysis of first 120 days revealed about 4000 Neutrino-candidates and a stable detector-setup with low backgrounds. The commissioning of the second (near) detector is expected for the beginning of 2013 and will provide maximum sensitivity for the experiment.

  19. [New therapy for AIDS: a double-edged sword].

    PubMed

    Foreman, M

    1996-01-01

    The main theme of the XI AIDS International Conference, held in Vancouver, was the new combination treatments using antiretroviral drugs to reduce the presence of the HIV virus. Clinical studies have shown a significant reduction in viral load due to using protease inhibitors. Although a promising treatment, its annual cost can reach $30,000. Activists voice their opinions on the high cost of these drugs. PMID:11364382

  20. Oxygen Therapy

    MedlinePlus

    Oxygen therapy is a treatment that provides you with extra oxygen. Oxygen is a gas that your body needs to function. Normally, your lungs absorb oxygen from the air you breathe. But some conditions ...

  1. Radiation Therapy

    MedlinePlus

    Radiation therapy is a cancer treatment. It uses high doses of radiation to kill cancer cells and stop them from ... half of all cancer patients receive it. The radiation may be external, from special machines, or internal, ...

  2. Radiation therapy

    MedlinePlus

    Radiation therapy uses high-powered x-rays, particles, or radioactive seeds to kill cancer cells. ... faster than normal cells in the body. Because radiation is most harmful to quickly growing cells, radiation ...

  3. Electroconvulsive therapy

    MedlinePlus

    Electroconvulsive therapy (ECT) uses an electric current to treat depression and some other mental illnesses. ... During ECT, the electric current triggers a seizure in the brain. Doctors believe that the seizure activity may help the brain "rewire" itself, which ...

  4. Electroconvulsive therapy

    MedlinePlus

    ... please enable JavaScript. Electroconvulsive therapy (ECT) uses an electric current to treat depression and some other mental illnesses. Description During ECT, the electric current triggers a seizure in the brain. Doctors believe ...

  5. Proton Therapy

    MedlinePlus

    ... nucleus is surrounded by electrons. In proton therapy, beams of fast-moving protons are used to destroy ... atoms to release proton, neutron, and helium ion beams. In this highly specialized form of radiosurgery , proton ...

  6. Hug Therapy.

    ERIC Educational Resources Information Center

    Johnson, Sally; Franke, Sue

    1997-01-01

    Describes Hug Therapy as used at the Allegheny County Head Start centers in Pennsylvania. Discusses the value of appropriate touch for healthy physical and emotional development. Addresses barriers to therapeutic touching and benefits to children and parents. (KB)

  7. Oxygen Therapy

    MedlinePlus

    ... therapy works, it helps to understand how your respiratory system works. This system is a group of organs and tissues that help you breathe. The respiratory system includes the airways and lungs. The airways carry ...

  8. Proton Therapy

    MedlinePlus

    ... in a much more confined way than conventional photon therapy thus allowing the radiation oncologist to use ... charge. Just as x-rays (also known as photons) are used to treat both benign and malignant ...

  9. Radionuclide Therapy

    NASA Astrophysics Data System (ADS)

    Zalutsky, M. R.

    Radionuclide therapy utilizes unsealed sources of radionuclides as a treatment for cancer or other pathological conditions such as rheumatoid arthritis. Radionuclides that decay by the emission of β and α particles, as well as those that emit Auger electrons, have been used for this purpose. In this chapter, radiochemical aspects of radionuclide therapy, including criteria for radionuclide selection, radionuclide production, radiolabeling chemistry, and radiation dosimetry are discussed.

  10. Laboratory assessment of anti-thrombotic therapy in heart failure, atrial fibrillation and coronary artery disease: insights using thrombelastography and a micro-titre plate assay of thrombogenesis and fibrinolysis.

    PubMed

    Lau, Y C; Xiong, Q; Ranjit, P; Lip, G Y H; Blann, A D

    2016-08-01

    As heart failure, coronary artery disease and atrial fibrillation all bring a risk of thrombosis, anti-thrombotic therapy is recommended. Despite such treatment, major cardiovascular events such as myocardial infarction and stroke still occur, implying inadequate suppression of thrombus formation. Accordingly, identification of patients whose haemostasis remains unimpaired by treatment is valuable. We compared indices for assessing thrombogenesis and fibrinolysis by two different techniques in patients on different anti-thrombotic agents, i.e. aspirin or warfarin. We determined fibrin clot formation and fibrinolysis by a microplate assay and thromboelastography, and platelet marker soluble P selectin in 181 patients with acute or chronic heart failure, coronary artery disease who were taking either aspirin or warfarin. Five thromboelastograph indices and four microplate assay indices were different on aspirin versus warfarin (p < 0.05). In multivariate regression analysis, only microplate assay indices rate of clot formation and rate of clot dissolution were independently related to aspirin or warfarin use (p ≤ 0.001). Five microplate assay indices, but no thrombelastograph index, were different (p < 0.001) in aspirin users. Three microplate assay indices were different (p ≤ 0.002) in warfarin users. The microplate assay indices of lag time and rate of clot formation were abnormal in chronic heart failure patients on aspirin, suggesting increased risk of thrombosis despite anti-platelet use. Soluble P selectin was lower in patients on aspirin (p = 0.0175) but failed to correlate with any other index of haemostasis. The microplate assay shows promise as a tool for dissecting thrombogenesis and fibrinolysis in cardiovascular disease, and the impact of antithrombotic therapy. Prospective studies are required to determine a role in predicting thrombotic risk. PMID:26942726

  11. Double layers and electrostatic shocks

    NASA Technical Reports Server (NTRS)

    Hershkowitz, N.

    1981-01-01

    It is shown that it is useful to define double layers and shocks so that the ion phase spaces of double layers are the mirror image (about zero ion velocity) of the ion phase spaces for laminar electrostatic shocks. The distinguishing feature is the direction of the free ion velocity. It is also shown that double layers can exist without the presence of trapped ions. The Bohm condition for double layers, that the ion drift velocity on the high potential side must be greater than the ion sound velocity, is shown to be related to a requirement of a lower limit on the Mach number of laminar electrostatic shocks

  12. Colored Flag by Double Refraction.

    ERIC Educational Resources Information Center

    Reid, Bill

    1994-01-01

    Describes various demonstrations that illustrate double refraction and rotation of the plane of polarization in stressed, transparent plastics, with the consequent production of colored designs. (ZWH)

  13. Apple Valley Double Star Workshop

    NASA Astrophysics Data System (ADS)

    Brewer, Mark

    2015-05-01

    The High Desert Astronomical Society hosts an annual double star workshop, where participants measure the position angles and separations of double stars. Following the New Generation Science Standards (NGSS), adopted by the California State Board of Education, participants are assigned to teams where they learn the process of telescope set-up and operation, the gathering of data, and the reduction of the data. Team results are compared to the latest epoch listed in the Washington Double Star Catalog (WDS) and papers are written for publication in the Journal of Double Star Observations (JDSO). Each team presents a PowerPoint presentation to their peers about actual hands-on astronomical research.

  14. Dual double field theory

    NASA Astrophysics Data System (ADS)

    Bergshoeff, Eric A.; Hohm, Olaf; Penas, Victor A.; Riccioni, Fabio

    2016-06-01

    We present the dual formulation of double field theory at the linearized level. This is a classically equivalent theory describing the duals of the dilaton, the Kalb-Ramond field and the graviton in a T-duality or O( D, D) covariant way. In agreement with previous proposals, the resulting theory encodes fields in mixed Young-tableau representations, combining them into an antisymmetric 4-tensor under O( D, D). In contrast to previous proposals, the theory also requires an antisymmetric 2-tensor and a singlet, which are not all pure gauge. The need for these additional fields is analogous to a similar phenomenon for "exotic" dualizations, and we clarify this by comparing with the dualizations of the component fields. We close with some speculative remarks on the significance of these observations for the full non-linear theory yet to be constructed.

  15. Neutrinoless Double Beta Decay

    NASA Astrophysics Data System (ADS)

    Cremonesi, Oliviero

    2016-05-01

    After more than 3/4 of century from its proposal, Neutrinoless Double Beta Decay (NLDBD) is still missing observation and continues to represent the only practical method for investigating the Dirac/Majorana nature of neutrinos. In case neutrinos would be Majorana particles, NLDBD would provide unique informations on their properties (absolute mass scale and Majorana phases). Boosted by the discovery of neutrino oscillations, a number of experiments with improved sensitivity have been proposed in the past decade. Some of them have recently started operation and others are ready to start. They will push the experimental sensitivity on the decay halflife beyond 1026 year, starting to analyze the region of the inverted mass hierarchy. The status and perspectives of the ongoing experimental effort are reviewed. Uncertainties coming from the calculation othe decay nuclear matrix elements (NME) as well as the recently suggested possibility of a relevant quenching of the axial coupling constant are also discussed.

  16. Double layer secure sketch

    NASA Astrophysics Data System (ADS)

    Li, Cai

    2012-09-01

    Secure sketch has been applied successfully in a wide variety of applications like cryptography, biometric authentication systems and so on. All of these secure sketches have properties in common namely error-tolerance and small entropy loss. The former ensures an input set w' can unlock the system if w' is substantially overlapped with a template set w while the latter means it is hard for an adversary to get the information of w even with the knowledge of s, which is produced by w and stored in the system publicly. In their constructions, they all consider w as a set of atomic elements. However, in the real word, it is very likely the elements in the template set are sets as well. In this paper, we propose a double layer secure sketch to address this issue.

  17. Doubled Color Codes

    NASA Astrophysics Data System (ADS)

    Bravyi, Sergey

    Combining protection from noise and computational universality is one of the biggest challenges in the fault-tolerant quantum computing. Topological stabilizer codes such as the 2D surface code can tolerate a high level of noise but implementing logical gates, especially non-Clifford ones, requires a prohibitively large overhead due to the need of state distillation. In this talk I will describe a new family of 2D quantum error correcting codes that enable a transversal implementation of all logical gates required for the universal quantum computing. Transversal logical gates (TLG) are encoded operations that can be realized by applying some single-qubit rotation to each physical qubit. TLG are highly desirable since they introduce no overhead and do not spread errors. It has been known before that a quantum code can have only a finite number of TLGs which rules out computational universality. Our scheme circumvents this no-go result by combining TLGs of two different quantum codes using the gauge-fixing method pioneered by Paetznick and Reichardt. The first code, closely related to the 2D color code, enables a transversal implementation of all single-qubit Clifford gates such as the Hadamard gate and the π / 2 phase shift. The second code that we call a doubled color code provides a transversal T-gate, where T is the π / 4 phase shift. The Clifford+T gate set is known to be computationally universal. The two codes can be laid out on the honeycomb lattice with two qubits per site such that the code conversion requires parity measurements for six-qubit Pauli operators supported on faces of the lattice. I will also describe numerical simulations of logical Clifford+T circuits encoded by the distance-3 doubled color code. Based on a joint work with Andrew Cross.

  18. Photodynamic Therapy

    PubMed Central

    Dougherty, Thomas J.; Gomer, Charles J.; Henderson, Barbara W.; Jori, Giulio; Kessel, David; Korbelik, Mladen; Moan, Johan; Peng, Qian

    2015-01-01

    Photodynamic therapy involves administration of a tumor-localizing photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug), followed by activation of the agent by light of a specific wavelength. This therapy results in a sequence of photochemical and photobiologic processes that cause irreversible photodamage to tumor tissues. Results from preclinical and clinical studies conducted worldwide over a 25-year period have established photodynamic therapy as a useful treatment approach for some cancers. Since 1993, regulatory approval for photodynamic therapy involving use of a partially purified, commercially available hematoporphyrin derivative compound (Photofrin®) in patients with early and advanced stage cancer of the lung, digestive tract, and genitourinary tract has been obtained in Canada, The Netherlands, France, Germany, Japan, and the United States. We have attempted to conduct and present a comprehensive review of this rapidly expanding field. Mechanisms of subcellular and tumor localization of photosensitizing agents, as well as of molecular, cellular, and tumor responses associated with photodynamic therapy, are discussed. Technical issues regarding light dosimetry are also considered. PMID:9637138

  19. Radiation Therapy Physics, 3rd Edition

    NASA Astrophysics Data System (ADS)

    Hendee, William R.; Ibbott, Geoffrey S.; Hendee, Eric G.

    2004-08-01

    The Third Edition of Radiation Therapy Physics addresses in concise fashion the fundamental diagnostic radiologic physics principles as well as their clinical implications. Along with coverage of the concepts and applications for the radiation treatment of cancer patients, the authors have included reviews of the most up-to-date instrumentation and critical historical links. The text includes coverage of imaging in therapy planning and surveillance, calibration protocols, and precision radiation therapy, as well as discussion of relevant regulation and compliance activities. It contains an updated and expanded section on computer applications in radiation therapy and electron beam therapy, and features enhanced user-friendliness and visual appeal with a new, easy-to-follow format, including sidebars and a larger trim size. With its user-friendly presentation and broad, comprehensive coverage of radiotherapy physics, this Third Edition doubles as a medical text and handy professional reference.

  20. [Testosterone therapy].

    PubMed

    Diemer, T; Hauptmann, A; Wagenlehner, F M E

    2016-04-01

    Hormone replacement therapy with testosterone has become well-established over the course of time. The initial substantial concerns with respect to complications and potential adverse events, particularly in older patients, were proven to be unfounded over time. Testosterone therapy has therefore gradually become a regular treatment modality in urological practice. It has also been shown to represent a valuable tool as supportive treatment for patients with erectile dysfunction and hypogonadism. A variety of testosterone preparations are available for treatment. Recent pharmaceutical developments have greatly improved the practicability and ease of administration for patients. Several guidelines have been developed that provide clearly formulated standards and instructions for indications, contraindications, application, risk factors and monitoring of testosterone therapy. Adverse events affecting the cardiovascular system and especially diseases of the prostate gland are of great importance, thus making the urologist the primary partner in the treatment of patients with testosterone deficiency. PMID:27067659

  1. Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy.

    PubMed

    Burwell, R Geoffrey; Aujla, Ranjit K; Grevitt, Michael P; Dangerfield, Peter H; Moulton, Alan; Randell, Tabitha L; Anderson, Susan I

    2009-01-01

    Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic

  2. Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

    PubMed Central

    2009-01-01

    Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic

  3. The double-mode Cepheids

    NASA Astrophysics Data System (ADS)

    Balona, L. A.

    1985-06-01

    Recent observational and theoretical results on double-mode Cepheids are reviewed. The likelihood that recently proposed candidate Cepheids are indeed Cepheids is evaluated. Periods, period ratios, and semi-amplitudes of the light and radial velocity variations of double-mode Cepheids are given. The physical and pulsational properties of double-mode Cepheids are discussed, reviewing evidence that these stars are Population I objects of high mass and that they all have the same mean effective temperature. The discovery of strong H-alpha emission occurring at seemingly random phases is addressed. Attempts to resolve the mass discrepancy problem of double-mode Cepheids, which results from observations showing that these Cepheids are indistinguishable from normal Cepheids of similar period, are reviewed along with attempts to find the cause of double-mode pulsation.

  4. What Is Music Therapy?

    MedlinePlus

    American Music Therapy Association Home Contact News Help/FAQ Members Only Login About Music Therapy & AMTA What is Music Therapy? Definition and Quotes ... is Music Therapy? Print Email Share What is Music Therapy What is Music Therapy? Music Therapy is the ...

  5. Latest Double Chooz results

    NASA Astrophysics Data System (ADS)

    Lasserre, Thierry; Double Chooz Collaboration

    2016-05-01

    I report the latest results from the Double Chooz experiment on the θ13 neutrino mixing angle. Two detectors are located at distances of 400 m and 1050 m from the reactor cores of the Chooz nuclear power station (France) to measure the disappearance of electron antineutrinos. The far detector has been taking data since 2011, accumulating a live time of 467.90 days (66.5 GW-ton-year). In this article we focus on the latest measurement using neutrino-induced neutron capture on hydrogen. A new analysis improved the signal efficiency and reduced the backgrounds and systematic uncertainties, leading to sin2 2θ 13 = 0.095+0.039 -0.038. When combined with the Gadolinium-based analysis this leads to sin2 2θ13 = 0.088+0.33 -0.033. The distortion from the prediction above a visible energy of 4 MeV is confirmed. The near detector started data taking in 2014 and first results shall be reported in 2016.

  6. Supported double membranes

    PubMed Central

    Murray, David H.; Tamm, Lukas K.; Kiessling, Volker

    2009-01-01

    Planar model membranes, like supported lipid bilayers and surface-tethered vesicles, have been proven to be useful tools for the investigation of complex biological functions in a significantly less complex membrane environment. In this study, we introduce a supported double membrane system that should be useful for studies that target biological processes in the proximity of two lipid bilayers such as the periplasm of bacteria and mitochondria or the small cleft between pre-and postsynaptic neuronal membranes. Large unilamellar vesicles (LUV) were tethered to a preformed supported bilayer by a biotin-streptavidin tether. We show from single particle tracking (SPT) experiments that these vesicle are mobile above the plane of the supported membrane. At higher concentrations, the tethered vesicles fuse to form a second continuous bilayer on top of the supported bilayer. The distance between the two bilayers was determined by fluorescence interference contrast (FLIC) microscopy to be between 16 and 24 nm. The lateral diffusion of labeled lipids in the second bilayer was very similar to that in supported membranes. SPT experiments with reconstituted syntaxin-1A show that the mobility of transmembrane proteins was not improved when compared with solid supported membranes. PMID:19236921

  7. Laser double Doppler flowmeter

    NASA Astrophysics Data System (ADS)

    Poffo, L.; Goujon, J.-M.; Le Page, R.; Lemaitre, J.; Guendouz, M.; Lorrain, N.; Bosc, D.

    2014-05-01

    The Laser Doppler flowmetry (LDF) is a non-invasive method for estimating the tissular blood flow and speed at a microscopic scale (microcirculation). It is used for medical research as well as for the diagnosis of diseases related to circulatory system tissues and organs including the issues of microvascular flow (perfusion). It is based on the Doppler effect, created by the interaction between the laser light and tissues. LDF measures the mean blood flow in a volume formed by the single laser beam, that penetrate into the skin. The size of this measurement volume is crucial and depends on skin absorption, and is not directly reachable. Therefore, current developments of the LDF are focused on the use of always more complex and sophisticated signal processing methods. On the other hand, laser Double Doppler Flowmeter (FL2D) proposes to use two laser beams to generate the measurement volume. This volume would be perfectly stable and localized at the intersection of the two laser beams. With FL2D we will be able to determine the absolute blood flow of a specific artery. One aimed application would be to help clinical physicians in health care units.

  8. Double acting bit holder

    DOEpatents

    Morrell, Roger J.; Larson, David A.; Ruzzi, Peter L.

    1994-01-01

    A double acting bit holder that permits bits held in it to be resharpened during cutting action to increase energy efficiency by reducing the amount of small chips produced. The holder consist of: a stationary base portion capable of being fixed to a cutter head of an excavation machine and having an integral extension therefrom with a bore hole therethrough to accommodate a pin shaft; a movable portion coextensive with the base having a pin shaft integrally extending therefrom that is insertable in the bore hole of the base member to permit the moveable portion to rotate about the axis of the pin shaft; a recess in the movable portion of the holder to accommodate a shank of a bit; and a biased spring disposed in adjoining openings in the base and moveable portions of the holder to permit the moveable portion to pivot around the pin shaft during cutting action of a bit fixed in a turret to allow front, mid and back positions of the bit during cutting to lessen creation of small chip amounts and resharpen the bit during excavation use.

  9. Pion double charge exchange reactions leading to double pionic atoms

    SciTech Connect

    Nieves, J.; Oset, E.; Vincente-Vacas, M.J. ); Hirenzaki, S.; Toki, H. )

    1992-10-20

    In this paper, the authors study theoretically pion double charge exchange reactions leading to double pionic atoms. The reaction cross-sections with two pions in the deeper bound pionic orbits in [sup 208]Pb are calculated with realistic pionic atom wave functions and distortion effects. The cross-sections are found to be d[sup 2] [sigma]/dEd[Omega] [approx] 10[sup [minus] 3] [minus] 10[sup [minus] 4] [mu]b/srMeV, which are only a small fraction of the double charge exchange.

  10. [Auricle therapy].

    PubMed

    Masip Sales, Mireia

    2005-05-01

    Auricle therapy is the method which diagnoses and treats the human body via the external ear. The author describes its simple application as its principal characteristics and contrasts these with the efficiency of its results. Furthermore, the author provides a wide range of therapeutic possibilities. PMID:15981969

  11. Proton therapy

    MedlinePlus

    ... skin redness in the radiation area, and temporary hair loss. AFTER THE PROCEDURE Following proton therapy, you should be able to resume your normal activities. You will likely see your doctor every 3 to 4 months for a follow-up exam.

  12. Multimodal Therapy.

    ERIC Educational Resources Information Center

    Lazarus, Arnold A.

    The multimodal therapy (MMT) approach provides a framework that facilitates systematic treatment selection in a broad-based, comprehensive and yet highly focused manner. It respects science, and data driven findings, and endeavors to use empirically supported methods when possible. Nevertheless, it recognizes that many issues still fall into the…

  13. Dance Therapy.

    ERIC Educational Resources Information Center

    Leventhal, Marcia B.

    1980-01-01

    Dance therapy deals with personal growth via body-mind interaction. A change in movement expression is believed to result in a personality or behavior change. The therapist is trained to become sensitive to movement expression as it relates to the psychological, motor, and cognitive development of the child. (JN)

  14. Double Radio Sources: Two Approaches

    NASA Astrophysics Data System (ADS)

    Valtonen, M. J.; Heinämäki, P.

    2000-02-01

    The theory of double radio sources is considered from two different points of view: the so called unified models and the slingshot model. First, observations and theory are discussed in 11 areas: (1) the dependence or independence of small-scale and large-scale jets from each other; (2) stability and existence of large-scale jets; (3) radio hot spots inside the lobes of double radio sources; (4) the relation of double-lobed quasars to radio galaxies; (5) polarization and other asymmetries between the two lobes and correlations among them; (6) the speeds of advance of radio lobes; (7) giant radio sources; (8) one-sided double radio sources; (9) multiple-sided double radio sources; (10) the origin of the Fanaroff-Riley classes of radio morphology; and (11) the origin of distance asymmetries of the radio lobes. Then five steps in building up a double radio source theory are discussed: (1) theory of galaxy mergers; (2) theory of black hole mergers; (3) theory of black hole interactions and ejections; (4) theory of radio lobe formation and evolution; and (5) radio jet theory. Finally, recent X-ray observations by ROSAT are discussed from the point of view of double radio source theory.

  15. Advanced double layer capacitors

    NASA Technical Reports Server (NTRS)

    Sarangapani, S.; Lessner, P.; Forchione, J.; Laconti, A. B.

    1989-01-01

    There is a need for large amounts of power to be delivered rapidly in a number of airborne and space systems. Conventional, portable power sources, such as batteries, are not suited to delivering high peak power pulses. The charge stored at the electrode-electrolyte double layer is, however, much more assessible on a short time scale. Devices exploiting this concept were fabricated using carbon and metal oxides (Pinnacle Research) as the electrodes and sulfuric acid as the electrolyte. The approach reported, replaces the liquid sulfuric acid electrolyte with a solid ionomer electrolyte. The challenge is to form a solid electrode-solid ionomer electrolyte composite which has a high capacitance per geometric area. The approach to maximize contact between the electrode particles and the ionomer was to impregnate the electrode particles using a liquid ionomer solution and to bond the solvent-free structure to a solid ionomer membrane. Ruthenium dioxide is the electrode material used. Three strategies are being pursued to provide for a high area electrode-ionomer contact: mixing of the RuOx with a small volume of ionomer solution followed by filtration to remove the solvent, and impregnation of the ionomer into an already formed RuOx electrode. RuOx powder and electrodes were examined by non-electrochemical techniques. X-ray diffraction has shown that the material is almost pure RuO2. The electrode structure depends on the processing technique used to introduce the Nafion. Impregnated electrodes have Nafion concentrated near the surface. Electrodes prepared by the evaporation method show large aggregates of crystals surrounded by Nafion.

  16. Anecdotal therapies.

    PubMed

    Millikan, L E

    1999-01-01

    Traditionally, many advances in medicine have been serendipitous. Are serendipitous and anecdotal synonymous? Many of our materia medica today relate to initial probes and anecdotal reports that matured to full investigation and therapeutic indications. The recent situation regarding Skin Cap is one that highlights the downside of this scenario. Several drugs in the US continue usage largely related to anecdotal indications, and anecdotal extension of legend indications is a standard for American Dermatology. The situation with systemic drugs, such as Trental, zinc preparations, imidazoles for extended indications, lysine and melatonin, all will be discussed. Topical preparations such as skin cap, cantharone, Vioform, all also are included in this category. It is important to place this topic in perspective in regards to geographic variation and therapeutic need. Many diseases lacking specific therapy are important targets for anecdotal therapy, and this will foster continued approaches in this area. The growing standardization of medicine and pharmaceutical regulation, threatens the anecdotal approach, but it provides still an important link to the future for some forms of therapy in diseases that are difficult to treat. Traditionally, the anecdote has been the first step in the therapeutic chain. Withering discovery of the benefits of the common fox glove in dropsy, was followed by many other anecdotes arriving via folk-medicine in the New World. This approach of utilizing folk medicine has now reached new heights, with very active searches by major pharmaceutical companies throughout the third world for remedies that may have potential. Couched with this is the history of anecdotal "snake-oil" remedies, that clearly had no benefit to anyone except the huckster marketing same. The excesses in this area of unproven and false therapies, led to the gradual organization of therapeutic trials and the Food and Drug Administration in the US as we know it today. The

  17. Three step double layers in the laboratory

    NASA Astrophysics Data System (ADS)

    Bailey, Andrew, III; Hershkowitz, Noah

    1988-01-01

    A new class of stationary double layer structure, with three or more distinct steps, is demonstrated in the laboratory. A large monotonic potential increase results from a series of smaller double layers. In many respects, these double layer structures resemble those inferred from satellite measurements of auroral double layers. This new class of double layer appears to depend on turbulence for its existence and to be a hybrid structure, intermediate between anomalous resistivity and BGK double layers.

  18. Particle therapy

    SciTech Connect

    Raju, M.R.

    1993-09-01

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics.

  19. [Anti-platelet actions of salicylates: in vivo, ex vivo and in vitro effects of choline salicylate].

    PubMed

    Irino, O; Saitoh, K; Ohkubo, K

    1985-07-01

    Effects of choline salicylate, sodium salicylate, choline chloride and acetylsalicylic acid on platelet aggregation in vivo, ex vivo and in vitro in mice were studied. These drugs all inhibited adenosine diphosphate (ADP)-induced respiratory depression, which is closely related to platelet aggregation in vivo, with choline salicylate showing the strongest inhibitory effect. Choline salicylate had a tendency to reduce the mortality of animals injected intravenously with endotoxin, but the other drugs had no such effect. The inhibitory effects of these drugs on ADP-induced platelet aggregation ex vivo were in the order of choline salicylate greater than acetylsalicylic acid congruent to sodium salicylate greater than choline chloride congruent to no effect, and plasma concentrations of protein-unbound salicylic acid at 1 hr after oral administration of drugs were in the order of choline salicylate greater than acetylsalicylic acid congruent to sodium salicylate. The in vitro effects of these drugs were in the order of choline salicylate congruent to sodium salicylate greater than choline chloride congruent to acetylsalicylic acid congruent to no effect. Therefore, it was considered that salicylic acid played an important role on the in vivo, ex vivo and in vitro effects of choline salicylate and that choline increased plasma concentrations of salicylic acid and consequently enhanced the in vivo and ex vivo effects of salicylic acid. Furthermore, the ex vivo effects of choline salicylate were found when ADP-induced platelet aggregation was measured with platelet-rich plasma prepared from blood collected with heparin as anti-coagulant, but not when blood was collected with citrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4043866

  20. Enhanced nitric oxide and cyclic GMP formation plays a role in the anti-platelet activity of simvastatin

    PubMed Central

    Chou, T-C; Lin, Y-F; Wu, W-C; Chu, K-M

    2008-01-01

    Background and purpose: It has been found that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert various vascular protective effects, beyond their cholesterol-lowering property, including inhibition of platelet-dependent thrombus formation. The objective of the present study was to determine whether the nitric oxide (NO)/cyclic GMP-mediated processes in platelets contribute to the anti-aggregatory activity of simvastatin. Experimental approach: After rabbit platelets were incubated with simvastatin for 5 min, aggregation was induced and the platelet aggregation, nitric oxide synthase activity, guanylyl cyclase activity, NO and cyclic GMP formation were measured appropriately. Key results: Treatment with simvastatin concentration-dependently inhibited platelet aggregation induced by collagen or arachidonic acid with an IC50 range of 52–158 μM. We also demonstrated that simvastatin (20–80 μM) concentration-dependently further enhanced collagen-induced NO and cyclic GMP formation through increasing NOS activity (from 2.64±0.12 to 3.52±0.21–5.10±0.14 μmol min−1 mg protein−1) and guanylyl cyclase activity (from 142.9±7.2 to 163.5±17.5–283.8±19.5 pmol min−1 mg protein−1) in the platelets. On the contrary, inhibition of platelet aggregation by simvastatin was markedly attenuated (by about 50%) by addition of a nitric oxide synthase inhibitor, a NO scavenger or a NO-sensitive guanylyl cyclase inhibitor. The anti-aggregatory effects of simvastatin were significantly increased by addition of a selective inhibitor of cyclic GMP phosphodiesterase. Conclusions and implications: Our findings indicate that enhancement of a NO/cyclic GMP-mediated process plays an important role in the anti-aggregatory activity of simvastatin. PMID:18264124

  1. Metabolomic investigation of the anti-platelet aggregation activity of ginsenoside Rk₁ reveals attenuated 12-HETE production.

    PubMed

    Ju, Hyun Kyoung; Lee, Jin Gyun; Park, Mi Kyung; Park, So-Jung; Lee, Chang Hoon; Park, Jeong Hill; Kwon, Sung Won

    2012-10-01

    Comprehensive metabolomics analysis is an effective method of measuring metabolite levels in the body following administration of a pharmaceutical compound and can allow for monitoring of the effects of the compound or assessment of appropriate treatment options for individual patients. In the present metabolomics study, samples pretreated with antiplatelet compounds were extracted and subjected to ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry. The acquired data were processed using peak clustering and evaluated by partial least-squares (PLS) and orthogonal projections to latent structures discriminant analyses (OPLS-DA). As a result, meaningful endogenous metabolites, namely eicosanoids and thromboxane B(2) (TXB(2)), were identified. TXB(2), a key element in platelet aggregation, was decreased upon ginsenoside Rk(1) treatment via inhibition of cyclooxygenase (COX) activity. One of the arachidonic acid (AA) metabolites, 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), was decreased significantly in the ginsenoside Rk(1)-treated platelets compared to the AA-induced group. In the mechanism study of ginsenoside Rk(1), a strong linkage to intracellular calcium levels, which induce platelet activation, was found. Additionally, the translocation of 12-LOX from cytosol to membrane, which is related with the intracellular calcium levels, was determined. Therefore, a decreased 12-HETE level induced by ginsenoside Rk(1) on antiplatelet aggregation is related to 12-LOX translocation resulting from decreased Ca(2+) levels. This study shows that global metabolomic analysis has potential for use in understanding the biological behavior of antiplatelet drugs. PMID:22873173

  2. Mechanical prophylaxis is a heparin-independent risk for anti-platelet factor 4/heparin antibody formation after orthopedic surgery.

    PubMed

    Bito, Seiji; Miyata, Shigeki; Migita, Kiyoshi; Nakamura, Mashio; Shinohara, Kazuhito; Sato, Tomotaro; Tonai, Takeharu; Shimizu, Motoyuki; Shibata, Yasuhiro; Kishi, Kazuhiko; Kubota, Chikara; Nakahara, Shinnosuke; Mori, Toshihito; Ikeda, Kazuo; Ota, Shusuke; Minamizaki, Takeshi; Yamada, Shigeru; Shiota, Naofumi; Kamei, Masataka; Motokawa, Satoru

    2016-02-25

    Platelet-activating antibodies, which recognize platelet factor 4 (PF4)/heparin complexes, induce spontaneous heparin-induced thrombocytopenia (HIT) syndrome or fondaparinux-associated HIT without exposure to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). This condition mostly occurs after major orthopedic surgery, implying that surgery itself could trigger this immune response, although the mechanism is unclear. To investigate how surgery may do so, we performed a multicenter, prospective study of 2069 patients who underwent total knee arthroplasty (TKA) or hip arthroplasty. Approximately half of the patients received postoperative thromboprophylaxis with UFH, LMWH, or fondaparinux. The other half received only mechanical thromboprophylaxis, including dynamic (intermittent plantar or pneumatic compression device), static (graduated compression stockings [GCSs]), or both. We measured anti-PF4/heparin immunoglobulins G, A, and M before and 10 days after surgery using an immunoassay. Multivariate analysis revealed that dynamic mechanical thromboprophylaxis (DMT) was an independent risk factor for seroconversion (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.34-3.02; P = .001), which was confirmed with propensity-score matching (OR, 1.99; 95% CI, 1.17-3.37; P = .018). For TKA, the seroconversion rates in patients treated with DMT but no anticoagulation and in patients treated with UFH or LMWH without DMT were similar, but significantly higher than in patients treated with only GCSs. The proportion of patients with ≥1.4 optical density units appeared to be higher among those treated with any anticoagulant plus DMT than among those not treated with DMT. Our study suggests that DMT increases risk of an anti-PF4/heparin immune response, even without heparin exposure. This trial was registered to www.umin.ac.jp/ctr as #UMIN000001366. PMID:26659923

  3. Species doubling and effective Lagrangians

    SciTech Connect

    Creutz, M.; Tytgat, M.

    1996-09-01

    Coupling gauge fields to the chiral currents from an effective Lagrangian for pseudoscalar mesons naturally gives rise to a species doubling phenomenon similar to that seen with fermionic fields in lattice gauge theory. 17 refs.

  4. A Double Pendulum "Art Machine"

    ERIC Educational Resources Information Center

    Romer, R. H.

    1970-01-01

    Describes a double pendulum apparatus and its mode of operation to produce a great variety of figures similar to Lissajous figures. The author suggests that several advanced physics topics can be studied with the aid of this instrument. Bibliography. (LC)

  5. Entanglement purification with double selection

    SciTech Connect

    Fujii, Keisuke; Yamamoto, Katsuji

    2009-10-15

    We investigate an entanglement purification protocol with double-selection process, which works under imperfect local operations. Compared with the usual protocol with single selection, this double-selection method has higher noise thresholds for the local operations and quantum communication channels and achieves higher fidelity of purified states. It also provides a yield comparable to that of the usual protocol with single selection. We discuss on general grounds how some of the errors which are introduced by local operations are left as intrinsically undetectable. The undetectable errors place a general upper bound on the purification fidelity. The double selection is a simple method to remove all the detectable errors in the first order, so that the upper bound on the fidelity is achieved in the low-noise regime. The double selection is further applied to purification of multipartite entanglement such as two-colorable graph states.

  6. Radiation Therapy (For Parents)

    MedlinePlus

    ... 5 Things to Know About Zika & Pregnancy Radiation Therapy KidsHealth > For Parents > Radiation Therapy Print A A ... many questions and concerns about it. About Radiation Therapy In radiation therapy, high-energy radiation from X- ...

  7. Esophagus Cancer: Palliative Therapy

    MedlinePlus

    ... your doctor about cancer of the esophagus? Palliative therapy for cancer of the esophagus Palliative therapy is ... therapy Electrocoagulation Laser ablation Argon plasma coagulation Radiation therapy External-beam radiation can often help relieve some ...

  8. Simulation of auroral double layers

    NASA Technical Reports Server (NTRS)

    Hubbard, R. F.; Joyce, G.

    1979-01-01

    Some basic properties of plasma double layers are deduced from a particle-in-cell computer simulation and related to parallel electric-field structures above the auroral regions. The simulation results on the processes leading to double-layer formation are examined, particularly in relation to the transient stage and double-layer structure and stability. It is concluded that: (1) a large potential difference applied to a finite-length plasma will be concentrated in a shocklike localized region instead of occurring over the entire length of the system; (2) the initial stage in double-layer formation is dominated by a large-potential pulse propagating in the direction of the induced electrostatic drift; (3) the entire potential is dropped over a specific scale length once the double layer has formed; and (4) this scale length is expected to be of the order of 1 km for a double layer above a discrete auroral arc with a potential of 10 kV and the electric-field vector parallel to the magnetic-field vector.

  9. The double burden.

    PubMed

    Faurholt-Jepsen, Daniel

    2013-07-01

    parameters. The population was followed up during treatment (2 and 5 months) to assess treatment outcome as well as after one year to assess their survival status. Based on data from 1,250 tuberculosis patients and 350 neighbourhood controls, we found that 38 and 21%, respectively, had impaired glycaemia, and that the prevalence of diabetes was 17 and 9% among tuberculosis patients and controls, respectively. This difference in prevalence between patients and controls was equivalent to an adjusted odds ratio of more than four, indicating a strong association between tuberculosis and diabetes. Furthermore, we found that diabetes was associated with tuberculosis among both participants with or without HIV co-infection. Despite the strong association, diabetes had only moderate clinical implications when the tuberculosis patients initiated the tuberculosis treatment; the patients with diabetes co-morbidity had a minor elevation in the immune response and more frequently reported to have fever. Furthermore, diabetes did not seem to delay time to sputum conversion during treatment. Nevertheless, diabetes co-morbidity led to impaired treatment outcome with slower recovery of weight and haemoglobin and a more than four times higher mortality rate within the initial phase of tuberculosis treatment. In conclusion, in the African region, the double burden of tuberculosis and diabetes is becoming a major health problem. Although the tuberculosis incidence has stabilized during the last decade, the increasing incidence of diabetes will possibly interfere with tuberculosis control and may, consequently, make the tuberculosis incidence increase again. Future research strategies should focus on enhanced diagnostic tools to identify tuberculosis patients with diabetes co-morbidity, and on the role of disease-disease, drug-disease and drug-drug interactions between tuberculosis and diabetes diseases and treatments. PMID:23809978

  10. Music Therapy: A Career in Music Therapy

    MedlinePlus

    About Music Therapy & Music Therapy Training M usic therapy is a healthcare profession that uses music to help individuals of all ages improve physical, ... grateful I chose a career as rewarding as music therapy. I love what I do each day!” Where ...

  11. The double loop mattress suture

    PubMed Central

    Biddlestone, John; Samuel, Madan; Creagh, Terry; Ahmad, Tariq

    2014-01-01

    An interrupted stitch type with favorable tissue characteristics will reduce local wound complications. We describe a novel high-strength, low-tension repair for the interrupted closure of skin, cartilage, and muscle, the double loop mattress stitch, and compare it experimentally with other interrupted closure methods. The performance of the double loop mattress technique in porcine cartilage and skeletal muscle is compared with the simple, mattress, and loop mattress interrupted sutures in both a novel porcine loading chamber and mechanical model. Wound apposition is assessed by electron microscopy. The performance of the double loop mattress in vivo was confirmed using a series of 805 pediatric laparotomies/laparoscopies. The double loop mattress suture is 3.5 times stronger than the loop mattress in muscle and 1.6 times stronger in cartilage (p ≤ 0.001). Additionally, the double loop mattress reduces tissue tension by 66% compared with just 53% for the loop mattress (p ≤ 0.001). Wound gapping is equal, and wound eversion appears significantly improved (p ≤ 0.001) compared with the loop mattress in vitro. In vivo, the double loop mattress performs as well as the loop mattress and significantly better than the mattress stitch in assessments of wound eversion and dehiscence. There were no episodes of stitch extrusion in our series of patients. The mechanical advantage of its intrinsic pulley arrangement gives the double loop mattress its favorable properties. Wound dehiscence is reduced because this stitch type is stronger and exerts less tension on the tissue than the mattress stitch. We advocate the use of this novel stitch wherever a high-strength, low-tension repair is required. These properties will enhance wound repair, and its application will be useful to surgeons of all disciplines. PMID:24698436

  12. 100 positive double-blind studies: enough or too little?

    NASA Astrophysics Data System (ADS)

    Tuner, Jan; Hode, Lars

    2000-06-01

    A major argument among the opponents of laser therapy has been the absence of scientific documentation. This was a valid position in the 80s and partly in the 90s. But today, is this still a sound argument. There are more than 2,000 published studies in the field, including meeting abstracts and anecdotal reports. The vast majority of these papers reports positive effects of LLLT in vitro and in vivo. It is fair to argue that negative results are less prone to be published, but certainly more than 80 percent of the published studies are positive. In the field of dentistry, for instance, the positive percentage is well above 90 percent. The present literature study will look at the heart of the positive documentation: the positive double blind studies. It may come as a surprise to many critics that there are more than 100 positive double blind studies in the field laser therapy. This is a god base for a further understanding of the effects of low level laser in the clinical setting. We must, however, be as critical as the sceptics themselves in order to obtain a constructive dialogue between 'attorneys' and sceptics. In this paper, a critical review of 100 positive double blind studies will be presented.

  13. Double metric, generalized metric, and α' -deformed double field theory

    NASA Astrophysics Data System (ADS)

    Hohm, Olaf; Zwiebach, Barton

    2016-03-01

    We relate the unconstrained "double metric" of the "α' -geometry" formulation of double field theory to the constrained generalized metric encoding the spacetime metric and b -field. This is achieved by integrating out auxiliary field components of the double metric in an iterative procedure that induces an infinite number of higher-derivative corrections. As an application, we prove that, to first order in α' and to all orders in fields, the deformed gauge transformations are Green-Schwarz-deformed diffeomorphisms. We also prove that to first order in α' the spacetime action encodes precisely the Green-Schwarz deformation with Chern-Simons forms based on the torsionless gravitational connection. This seems to be in tension with suggestions in the literature that T-duality requires a torsionful connection, but we explain that these assertions are ambiguous since actions that use different connections are related by field redefinitions.

  14. Cancer Therapy

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The patient shown is undergoing cancer radiation treatment in a hospital-like atmosphere but he is not in a hospital. The treatment room is at NASA's Lewis Research Center, Cleveland, Ohio. It is a converted portion of the Center's cyclotron facility, originally designed for radiation studies related to nuclear propulsion for aircraft and spacecraft. Under an agreement between the Center and the Cleveland Clinic Foundation, the 50 million volt cyclotron is now being used to evaluate the effectiveness of "fast neutron" therapy in the treatment of cancerous tumors.

  15. 32 CFR 199.8 - Double coverage.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Double coverage. 199.8 Section 199.8 National... CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.8 Double coverage. (a... insurance plans do not exceed the total charges. (b) Double coverage plan. A double coverage plan is one...

  16. 32 CFR 199.8 - Double coverage.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Double coverage. 199.8 Section 199.8 National... CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.8 Double coverage. (a... insurance plans do not exceed the total charges. (b) Double coverage plan. A double coverage plan is one...

  17. 32 CFR 199.8 - Double coverage.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Double coverage. 199.8 Section 199.8 National... CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.8 Double coverage. Link to an... charges. (b) Double coverage plan. A double coverage plan is one of the following: (1) Insurance plan....

  18. Anti-spacer double patterning

    NASA Astrophysics Data System (ADS)

    Hyatt, Michael; Huang, Karen; DeVilliers, Anton; Slezak, Mark; Liu, Zhi

    2014-03-01

    With extreme UV not ready for HVM for the 20nm and 14nm nodes, double patterning options that extend the use of 193nm immersion lithography beyond the optical resolution limits, such as LELE (Litho-Etch-Litho-Etch) and SADP (Self Aligned Double Patterning), are being used for critical layers for these nodes. LELE requires very stringent overlay capability of the optical exposure tool. The spacer scheme of SADP starts with a conformal film of material around the mandrels and etched along the mandrel sidewalls to form patterns with doubled frequency. SADP, while having the advantage of being a self-aligned process, adds a number of process steps and strict control of the mandrel profile is required. In this paper, we will demonstrate a novel technique - ASDP (Anti-Spacer Double Patterning), which uses only spin-on materials to achieve self-aligned double patterning. After initial resist patterning, an Anti-Spacer Generator (ASG) material is coated on the resist pattern to create the developable spacer region. Another layer of material is then coated and processed to generate the second pattern in between the first resist pattern. We were able to define 37.5nm half pitch pattern features using this technique as well as sub-resolution features for an asymmetric pattern. In this paper we will review the capability of the process in terms of CD control and LWR (line width roughness) and discuss the limitations of the process.

  19. New double soft emission theorems

    NASA Astrophysics Data System (ADS)

    Cachazo, Freddy; He, Song; Yuan, Ellis Ye

    2015-09-01

    We study the behavior of the tree-level S-matrix of a variety of theories as two particles become soft. By analogy with the recently found subleading soft theorems for gravitons and gluons, we explore subleading terms in double soft emissions. We first consider double soft scalar emissions and find subleading terms that are controlled by the angular momentum operator acting on hard particles. The order of the subleading theorems depends on the presence or not of color structures. Next we obtain a compact formula for the leading term in a double soft photon emission. The theories studied are a special Galileon, Dirac-Born-Infeld, Einstein-Maxwell-Scalar, nonlinear sigma model and Yang-Mills-Scalar. We use the recently found Cachazo-He-Yuan representation of these theories in order to give a simple proof of the leading order part of all these theorems.

  20. Double field theory inspired cosmology

    SciTech Connect

    Wu, Houwen; Yang, Haitang E-mail: hyanga@scu.edu.cn

    2014-07-01

    Double field theory proposes a generalized spacetime action possessing manifest T-duality on the level of component fields. We calculate the cosmological solutions of double field theory with vanishing Kalb-Ramond field. It turns out that double field theory provides a more consistent way to construct cosmological solutions than the standard string cosmology. We construct solutions for vanishing and non-vanishing symmetry preserving dilaton potentials. The solutions assemble the pre- and post-big bang evolutions in one single line element. Our results show a smooth evolution from an anisotropic early stage to an isotropic phase without any special initial conditions in contrast to previous models. In addition, we demonstrate that the contraction of the dual space automatically leads to both an inflation phase and a decelerated expansion of the ordinary space during different evolution stages.

  1. Double patterning compliant logic design

    NASA Astrophysics Data System (ADS)

    Ma, Yuangsheng; Sweis, Jason; Bencher, Chris; Deng, Yunfei; Dai, Huixiong; Yoshida, Hidekazu; Gisuthan, Bimal; Kye, Jongwook; Levinson, Harry J.

    2011-04-01

    Double patterning technology (DPT) is the only solution to enable the scaling for advanced technology nodes before EUV or any other advanced patterning techniques become available. In general, there are two major double patterning techniques: one is Litho-Etch-Litho-Etch (LELE), and the other is sidewall spacer technology, a Self-Aligned Double Patterning technique (SADP). While numerous papers have previously demonstrated these techniques on wafer process capabilities and processing costs, more study needs to be done in the context of standard cell design flow to enable their applications in mass production. In this paper, we will present the impact of DPT on logic designs, and give a thorough discussion on how to make DPT-compliant constructs, placement and routing using examples with Cadence's Encounter Digital Implementation System (EDI System).

  2. Double ionization of atomic cadmium

    SciTech Connect

    Linusson, P.; Fritzsche, S.; Eland, J. H. D.; Hedin, L.; Karlsson, L.; Feifel, R.

    2011-02-15

    We have recorded the double photoionization spectrum of atomic Cd at four different photon energies in the range 40-200 eV. The main channel is single ionization and subsequent decay of excited Cd{sup +} states, some involving Coster-Kronig processes, whereas direct double ionization is found to be weak. The decay of the excited Cd{sup +} states shows a strong selectivity, related to the configuration of the final state. Double ionization leading to the Cd{sup 2+} ground state is investigated in some detail and is found to proceed mainly through ionization and decay of 4d correlation satellites. The most prominent autoionization peaks have been identified with the aid of quantum-mechanical calculations.

  3. Attosecond Double-Slit Experiment

    SciTech Connect

    Lindner, F.; Schaetzel, M.G.; Baltuska, A.; Goulielmakis, E.; Walther, H.; Krausz, F.; Milosevic, D.B.; Bauer, D.; Becker, W.; Paulus, G.G.

    2005-07-22

    A new scheme for a double-slit experiment in the time domain is presented. Phase-stabilized few-cycle laser pulses open one to two windows (slits) of attosecond duration for photoionization. Fringes in the angle-resolved energy spectrum of varying visibility depending on the degree of which-way information are measured. A situation in which one and the same electron encounters a single and a double slit at the same time is observed. The investigation of the fringes makes possible interferometry on the attosecond time scale. From the number of visible fringes, for example, one derives that the slits are extended over about 500 as.

  4. Double stranded nucleic acid biochips

    DOEpatents

    Chernov, Boris; Golova, Julia

    2006-05-23

    This invention describes a new method of constructing double-stranded DNA (dsDNA) microarrays based on the use of pre-synthesized or natural DNA duplexes without a stem-loop structure. The complementary oligonucleotide chains are bonded together by a novel connector that includes a linker for immobilization on a matrix. A non-enzymatic method for synthesizing double-stranded nucleic acids with this novel connector enables the construction of inexpensive and robust dsDNA/dsRNA microarrays. DNA-DNA and DNA-protein interactions are investigated using the microarrays.

  5. Double-Chooz Neutrino Experiment

    NASA Astrophysics Data System (ADS)

    Palomares, Carmen; Double Chooz Collaboration

    2011-12-01

    The Double Chooz experiment will use the electron anti-neutrinos produced by the Chooz nuclear power station to search for a non-vanishing value of the θ13 neutrino mixing angle. Double Chooz will be the first of a new generation of neutrino experiments using identical detectors at different distances from the neutrino source to reduce the systematic errors due to the uncertainties on the neutrino flux and to the detector acceptance. The far detector will be operative by the beginning of 2011. Installation of the near detector will occur in 2012.

  6. Robotic Therapy

    PubMed Central

    Krebs, H. I.; Hogan, N.

    2012-01-01

    The last two decades have seen a remarkable shift in the neuro-rehabilitation paradigm. Neuroscientists and clinicians moved away from the perception that the brain is static and hardwired, to a new dynamic understanding that plasticity is a fundamental property of the adult human brain and might be harnessed to remap or create new neural pathways. Capitalizing on this innovative understanding, we introduced a paradigm shift in the clinical practice in 1989 when we initiated the development of the MIT-Manus robot for neuro-rehabilitation and deployed it in the clinic in 1994 10. Since then, we and others have developed and tested a multitude of robotic devices for stroke, spinal cord injury, cerebral palsy, multiple sclerosis, and Parkinson’s disease. Here we discuss whether robotic therapy has achieved a level of maturity to justify its broad adoption in the clinical realm as a tool for motor recovery. PMID:23080044

  7. Intrapleural therapy.

    PubMed

    Huggins, J Terrill; Doelken, Peter; Sahn, Steven A

    2011-08-01

    Numerous intrapleural therapies have been adopted to treat a vast array of pleural diseases. The first intrapleural therapies proposed focused on the use of fibrinolytics and DNase to promote fluid drainage in empyema. Numerous case series and five randomized controlled trials have been published to determine the outcomes of fibrinolytics in empyema treatment. In the largest randomized trial, the use of streptokinase had no reduction in mortality, decortication rates or hospital days compared with placebo in the treatment of empyema. Criticism over study design and patient selection may have potentially affected the outcomes in this study. The development of dyspnoea is common in the setting of malignant pleural effusions. Pleural fluid evacuation followed by pleurodesis is often attempted. Numerous sclerosing agents have been studied, with talc emerging as the most effective agent. Small particle size of talc should be avoided because of increased systemic absorption potentiating toxicity, such as acute lung injury. Over the past several years, the use of chronic indwelling pleural catheters have emerged as the preferred modality in the treating a symptomatic malignant pleural effusion. For patients with malignant-related lung entrapment, pleurodesis often fails due to the presence of visceral pleural restriction; however, chronic indwelling pleural catheters are effective in palliation of dyspnoea. Finally, the use of staphylococcal superantigens has been proposed as a therapeutic model for the treatment of non-small lung cancer. Intrapleural instillation of staphylococcal superantigens increased median survival by 5 months in patients with non-small cell lung cancer with a malignant pleural effusion. PMID:21672085

  8. Biphoton double-slit experiment

    SciTech Connect

    Brida, G.; Cagliero, E.; Falzetta, G.; Genovese, M.; Gramegna, M.; Predazzi, E.

    2003-09-01

    In this paper we present a double-slit experiment where two indistinguishable photons produced by type-I parametric down-conversion are each sent to a well-defined slit. Data about the diffraction and interference patterns for coincidences are presented and discussed. An analysis of these data allows a test of standard quantum mechanics against the de Broglie-Bohm theory.

  9. A Double-Minded Fractal

    ERIC Educational Resources Information Center

    Simoson, Andrew J.

    2009-01-01

    This article presents a fun activity of generating a double-minded fractal image for a linear algebra class once the idea of rotation and scaling matrices are introduced. In particular the fractal flip-flops between two words, depending on the level at which the image is viewed. (Contains 5 figures.)

  10. The double well mass filter

    SciTech Connect

    Gueroult, Renaud; Fisch, Nathaniel J.; Rax, Jean-Marcel

    2014-02-15

    Various mass filter concepts based on rotating plasmas have been suggested with the specific purpose of nuclear waste remediation. We report on a new rotating mass filter combining radial separation with axial extraction. The radial separation of the masses is the result of a “double-well” in effective radial potential in rotating plasma with a sheared rotation profile.

  11. Double heterojunction bipolar phototransistor model

    NASA Astrophysics Data System (ADS)

    Horak, Michal

    2003-07-01

    An analytical mathematical model of the double heterojunction NpN bipolar phototransistor with abrupt heterojunctions in three terminal configuration is presented. The thermionic-filed emission and diffusion of injected carriers is considered and the Ebers-Moll type relations for the collector and emitter current are obtained. Several steady state characteristics of the phototransistor structure are calculated (optical gain, quantum efficiency, responsivity).

  12. The double well mass filter

    DOE PAGESBeta

    Gueroult, Renaud; Rax, Jean -Marcel; Fisch, Nathaniel J.

    2014-02-03

    Various mass filter concepts based on rotating plasmas have been suggested with the specific purpose of nuclear waste remediation. We report on a new rotating mass filter combining radial separation with axial extraction. Lastly, the radial separation of the masses is the result of a “double-well” in effective radial potential in rotating plasma with a sheared rotation profile.

  13. Complex Disease, Partial Revascularization, and Adverse Outcomes in Patients Treated With Long-Term Warfarin Therapy Who Underwent Percutaneous Coronary Intervention.

    PubMed

    Yazji, Khaled; Kakhi, Sorayya; Ossei-Gerning, Nick; Choudhury, Anirban; Anderson, Richard; Kinnaird, Tim

    2015-08-01

    Patients treated with warfarin who undergo percutaneous coronary intervention (PCI) present a difficult therapeutic problem. Their baseline demographics, procedural characteristics, and 12-month outcomes are poorly defined. We conducted a retrospective analysis of all patients who underwent PCI at a major UK Cardiac Center from 2012 to 2013. Of the 2,675 patients who underwent PCI, 155 were on long-term warfarin treatment (5.8%). Patients on warfarin were older and more likely to have significant co-morbidity than those not on warfarin. The modified Mehran bleed score was higher in patients treated with warfarin versus those not treated (19.0 ± 5.8 vs 15.4 ± 8.0, p = 0.004). Baseline SYNTAX scores were higher in the patients treated with warfarin (18.5 ± 9.1 vs 12.4 ± 3.8, p = 0.0006) as were residual SYNTAX scores (8.3 ± 1.1 vs 3.8 ± 5.9, p = 0.001). Bare metal stents were more frequently used in warfarin-treated patients than those not treated (44.8% vs 26.3%, p <0.0001). Antiplatelet monotherapy was prescribed after PCI in 14.4% of patients treated with warfarin and 0.7% of non-warfarin (p <0.0001), whereas average dual anti-platelet therapy duration was also significantly shorter (4.3 vs 10.7 months, p <0.0001). At 1-year follow-up, target-vessel revascularization (6.5% vs 3.3%, p <0.05), stent thrombosis (5.0% vs 2.6%, p = 0.14), death (10.1% vs 4.6%, p <0.01), and target-vessel revascularization/stent thrombosis/death (21.6% vs 10.5%, p = 0.004) were all more common in the warfarin cohort. In conclusion, patients treated with warfarin who need PCI are a complex cohort, more likely to receive incomplete revascularization, less intense, and shorter durations of antiplatelet therapy, and have adverse 1-year outcomes. More trials of both current DES and newer DES technologies in warfarin-treated patients are needed. PMID:26048850

  14. Keepers of the double stars

    NASA Astrophysics Data System (ADS)

    Tenn, Joseph S.

    2013-03-01

    Astronomers have long tracked double stars in efforts to find those that are gravitationally-bound binaries and then to determine their orbits. Early catalogues by the Herschels, Struves, and others began with their own discoveries. In 1906 court reporter and amateur astronomer Sherburne Wesley Burnham published a massive double star catalogue containing data from many observers on more than 13,000 systems. Lick Observatory astronomer Robert Grant Aitken produced a much larger catalogue in 1932 and coordinated with Robert Innes of Johannesburg, who catalogued the southern systems. Aitken maintained and expanded Burnham's records of observations on handwritten file cards, and eventually turned them over to the Lick Observatory, where astrometrist Hamilton Jeffers further expanded the collection and put all the observations on punched cards. With the aid of Frances M. "Rete" Greeby he made two catalogues: an Index Catalogue with basic data about each star, and a complete catalogue of observations, with one observation per punched card. He enlisted Willem van den Bos of Johannesburg to add southern stars, and together they published the Index Catalogue of Visual Double Stars, 1961.0. As Jeffers approached retirement he became greatly concerned about the disposition of the catalogues. He wanted to be replaced by another "double star man," but Lick Director Albert E. Whitford had the new 120-inch reflector, the world's second largest telescope, and he wanted to pursue modern astrophysics instead. Jeffers was vociferously opposed to turning over the card files to another institution, and especially against their coming under the control of Kaj Strand of the United States Naval Observatory. In the end the USNO got the files and has maintained the records ever since, first under Charles Worley, and, since 1997, under Brian Mason. Now called the Washington Double Star Catalog (WDS), it is completely online and currently contains more than 1,200,000 measures of more than 125

  15. Laser therapy for cancer

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000905.htm Laser therapy for cancer To use the sharing features ... Lasers are also used on the skin. How Laser Therapy is Used Laser therapy can be used ...

  16. Living with Oxygen Therapy

    MedlinePlus

    ... page from the NHLBI on Twitter. Living With Oxygen Therapy Oxygen therapy helps many people function better and be ... chronic obstructive pulmonary disease) Although you may need oxygen therapy continuously or for long periods, it doesn' ...

  17. Targeted therapies for cancer

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000902.htm Targeted therapies for cancer To use the sharing features on ... cells so they cannot spread. How Does Targeted Therapy Work? Targeted therapy drugs work in a few ...

  18. American Music Therapy Association

    MedlinePlus

    American Music Therapy Association Home Contact News Help/FAQ Members Only Login Quick Links Facts About Music Therapy Qualifications ... with AMTA Sponsor AMTA Events Social Networking Support Music Therapy When you shop at AmazonSmile, Amazon will ...

  19. American Art Therapy Association

    MedlinePlus

    ... Educational Standards Approved Art Therapy Master’s Programs Professional Development Job Board ...Read more Approved Art Therapy Master’s ... Public Policy Insurance Reimbursement Licensure Public Policy Professional Development Annual Conference Approved Art Therapy Master's Programs Awards & ...

  20. External Beam Therapy (EBT)

    MedlinePlus

    ... Physician Resources Professions Site Index A-Z External Beam Therapy (EBT) External beam therapy (EBT) is a ... follow-up should I expect? What is external beam therapy and how is it used? External beam ...

  1. A laboratory investigation of potential double layers

    NASA Technical Reports Server (NTRS)

    Leung, Philip

    1987-01-01

    In a triple plasma device, the injection of electron current from the source chamber to the target chamber causes the formation of a potential double layer. At a low current density, the space charge of the injected current produces a virtual cathode-type potential double layer. This double layer is stable, and various wave instabilities are observed to associate with this double layer. As the current density is increased, the double layer becomes unstable, and a moving double layer results. As the current density is increased further, the enhanced ionization causes the neutralization of the space charge of the electron beam, and the beam plasma discharge is ignited.

  2. A laboratory investigation of potential double layers

    NASA Technical Reports Server (NTRS)

    Leung, Philip

    1987-01-01

    In a triple plasma device, the injection of electron current from the source chamber to the target chamber causes the formation of a potential double layer. At a low current density, the space charge of the injected current produces a virtual cathode-type potential double layer. This double layer is stable and various wave instabilities are observed to associate with this double layer. As the current density is increased, the double layer becomes unstable and a moving double layer results. As the current density is increased further, the enhanced ionization causes the neutralization of the space charge of the electron beam and the 'beam plasma discharge' is ignited.

  3. Double Photoionization into Double Core-Hole States in Xe

    SciTech Connect

    Hikosaka, Y.; Kaneyasu, T.; Shigemasa, E.; Lablanquie, P.; Penent, F.; Eland, J. H. D.; Aoto, T.; Ito, K.

    2007-05-04

    Double photoionization (DPI) leading to double core-hole states of Xe{sup 2+} 4d{sup -2} has been studied using a magnetic bottle time-of-flight spectrometer. The assignments of the Xe{sup 2+} 4d{sup -2} states are confirmed by the Auger lines extracted from fourfold coincidences including two photoelectrons and two Auger electrons. It is estimated that the core-core DPI into Xe{sup 2+} 4d{sup -2} at a photon energy of 301.6 eV has a favored cross section of about 0.3 MB. The intense core-core DPI is due to mixing of the 4d{sup -2} continuum with the 4p single photoionization, which is manifested in the relative intensities of the Xe{sup 2+} 4d{sup -2} components.

  4. Double photoionization into double core-hole states in Xe.

    PubMed

    Hikosaka, Y; Lablanquie, P; Penent, F; Kaneyasu, T; Shigemasa, E; Eland, J H D; Aoto, T; Ito, K

    2007-05-01

    Double photoionization (DPI) leading to double core-hole states of Xe2+ 4d(-2) has been studied using a magnetic bottle time-of-flight spectrometer. The assignments of the Xe2+ 4d(-2) states are confirmed by the Auger lines extracted from fourfold coincidences including two photoelectrons and two Auger electrons. It is estimated that the core-core DPI into Xe2+ 4d(-2) at a photon energy of 301.6 eV has a favored cross section of about 0.3 MB. The intense core-core DPI is due to mixing of the 4d(-2) continuum with the 4p single photoionization, which is manifested in the relative intensities of the Xe2+ 4d(-2) components. PMID:17501570

  5. Controversial therapies.

    PubMed

    Silver, L B

    1995-01-01

    Parents of children or adolescents with disabilities want the best treatment. They are vulnerable to any person who reports having a quick solution and possibly a cure. It is important that professionals be informed of these controversial therapies so that they can educate parents on what is known about these treatments. There is a relationship between brain function and nutrition, as well as between brain function and allergic reactions. These relations appear to be true for children with learning disabilities, attention deficit hyperactivity disorder, and other neurologic disorders. At this time, however, we do not understand these relationships and there are no known treatments based on these relationships that have been shown to be clinically successful. Professionals must educate parents on proposed new treatments. Parents need to ask themselves why this amazing approach is not used by everyone. If the person proposing the treatment tells them that "most professionals are biased and do not believe the findings because they are different from the traditional treatments," they should feel free to ask to see the data supporting the concept and the treatment. They should not accept without question popular books published by the person proposing the treatment or information provided in a flyer or on a television show by the person proposing the treatment. They should not put their son or daughter through something unproved and unlikely to help. PMID:7751563

  6. Cryoprecipitate therapy

    PubMed Central

    Nascimento, B.; Goodnough, L. T.; Levy, J. H.

    2014-01-01

    Cryoprecipitate, originally developed as a therapy for patients with antihaemophilic factor deficiency, or haemophilia A, has been in use for almost 50 yr. However, cryoprecipitate is no longer administered according to its original purpose, and is now most commonly used to replenish fibrinogen levels in patients with acquired coagulopathy, such as in clinical settings with haemorrhage including cardiac surgery, trauma, liver transplantation (LT), or obstetric haemorrhage. Cryoprecipitate is a pooled product that does not undergo pathogen inactivation, and its administration has been associated with a number of adverse events, particularly transmission of blood-borne pathogens and transfusion-related acute lung injury. As a result of these safety concerns, along with emerging availability of alternative fibrinogen preparations, cryoprecipitate has been withdrawn from use in a number of European countries. Compared with the plasma from which it is prepared, cryoprecipitate contains a high concentration of coagulation factor VIII, coagulation factor XIII, and fibrinogen. Cryoprecipitate is usually licensed by regulatory authorities for the treatment of hypofibrinogenaemia, and recommended for supplementation when plasma fibrinogen levels decrease below 1 g litre−1; however, this threshold is empiric and is not based on solid clinical evidence. Consequently, there is uncertainty over the appropriate dosing and optimal administration of cryoprecipitate, with some guidelines from professional societies to guide clinical practice. Randomized, controlled trials are needed to determine the clinical efficacy of cryoprecipitate, compared with the efficacy of alternative preparations. These trials will allow the development of evidence-based guidelines in order to inform physicians and guide clinical practice. PMID:24972790

  7. Double layers and double wells in arbitrary degenerate plasmas

    NASA Astrophysics Data System (ADS)

    Akbari-Moghanjoughi, M.

    2016-06-01

    Using the generalized hydrodynamic model, the possibility of variety of large amplitude nonlinear excitations is examined in electron-ion plasma with arbitrary electron degeneracy considering also the ion temperature effect. A new energy-density relation is proposed for plasmas with arbitrary electron degeneracy which reduces to the classical Boltzmann and quantum Thomas-Fermi counterparts in the extreme limits. The pseudopotential method is employed to find the criteria for existence of nonlinear structures such as solitons, periodic nonlinear structures, and double-layers for different cases of adiabatic and isothermal ion fluids for a whole range of normalized electron chemical potential, η0, ranging from dilute classical to completely degenerate electron fluids. It is observed that there is a Mach-speed gap in which no large amplitude localized or periodic nonlinear excitations can propagate in the plasma under consideration. It is further revealed that the plasma under investigation supports propagation of double-wells and double-layers the chemical potential and Mach number ranges of which are studied in terms of other plasma parameters. The Mach number criteria for nonlinear waves are shown to significantly differ for cases of classical with η0 < 0 and quantum with η0 > 0 regimes. It is also shown that the localized structure propagation criteria possess significant dissimilarities for plasmas with adiabatic and isothermal ions. Current research may be generalized to study the nonlinear structures in plasma containing positrons, multiple ions with different charge states, and charged dust grains.

  8. Monocular Elevation Deficiency - Double Elevator Palsy

    MedlinePlus

    ... Eye Terms Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? ...

  9. Monocular Elevation Deficiency - Double Elevator Palsy

    MedlinePlus

    ... Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? Monocular Elevation Deficiency, also known by the ...

  10. Bifurcation structure of successive torus doubling

    NASA Astrophysics Data System (ADS)

    Sekikawa, Munehisa; Inaba, Naohiko; Yoshinaga, Tetsuya; Tsubouchi, Takashi

    2006-01-01

    The authors discuss the “embryology” of successive torus doubling via the bifurcation theory, and assert that the coupled map of a logistic map and a circle map has a structure capable of generating infinite number of torus doublings.

  11. Five-photon double ionization of helium

    NASA Astrophysics Data System (ADS)

    Li, Y.; Pindzola, M. S.; Colgan, J.

    2016-03-01

    A time-dependent close-coupling method is used to calculate the five-photon double ionization of He. It is found that the generalized cross section used in the past for two-photon double ionization of He cannot be extended to five-photon double ionization of He. Therefore only five-photon double ionization probabilities that depend on specific radiation field pulses can be calculated.

  12. Minimal Doubling and Point Splitting

    SciTech Connect

    Creutz, M.

    2010-06-14

    Minimally-doubled chiral fermions have the unusual property of a single local field creating two fermionic species. Spreading the field over hypercubes allows construction of combinations that isolate specific modes. Combining these fields into bilinears produces meson fields of specific quantum numbers. Minimally-doubled fermion actions present the possibility of fast simulations while maintaining one exact chiral symmetry. They do, however, introduce some peculiar aspects. An explicit breaking of hyper-cubic symmetry allows additional counter-terms to appear in the renormalization. While a single field creates two different species, spreading this field over nearby sites allows isolation of specific states and the construction of physical meson operators. Finally, lattice artifacts break isospin and give two of the three pseudoscalar mesons an additional contribution to their mass. Depending on the sign of this mass splitting, one can either have a traditional Goldstone pseudoscalar meson or a parity breaking Aoki-like phase.

  13. Double Lambda and Xi hypernuclei

    NASA Astrophysics Data System (ADS)

    Nakazawa, Kazuma

    2014-09-01

    Nuclei with double strangeness (S = -2) provide the key information to understand Baryon-Baryon interaction under the SU(3)f symmetry. Therefore we have carried out the experiments at KEK for quarter a century. Recently, the interaction in S = -2 sector is noted to derive the information of the EOS of neutron star. The Lambda-Lambda interaction has been presented to be weak attractive by NAGARA event which showed the production and decay of 6He double-hypernucleus. The event also presented the lower mass limit of H dibaryon. In other five events, we obtained the knowledge about an excitation level of 10Be double-hypernucleus under the consistency with NAGARA event. Moreover, very recently, we have discovered a Xi-14N system which was deeply bound far from the atomic 3D level (0.17 MeV) for a captured Xi hyperon. Since a 8Li nucleus was associated with the decay of one of twin-hypernuclei, the event was uniquely identified as Xi- + 14N ==> 10BeL + 5HeL. The system was selected from 8 million pictures on the test running for development of ``Overall Scanning'' to be used in the coming experiment. This is the first evidence of Xi hypernucleus to be bound and it is impacting for the study of Xi-N interaction. At J-PARC facility, for the further study of hyperon-hyperon interaction, we plan to perform the E07 experiment at J-PARC. In the workshop, we will review the above knowledge obtained by the experiments at KEK-PS, and discuss developed technologies to detected 102 or more double-hypernuclei in the E07 experiment at J-PARC. Nuclei with double strangeness (S = -2) provide the key information to understand Baryon-Baryon interaction under the SU(3)f symmetry. Therefore we have carried out the experiments at KEK for quarter a century. Recently, the interaction in S = -2 sector is noted to derive the information of the EOS of neutron star. The Lambda-Lambda interaction has been presented to be weak attractive by NAGARA event which showed the production and decay of 6He

  14. Hierarchy in a double braneworld

    SciTech Connect

    Guerrero, Rommel; Rodriguez, R. Omar; Melfo, Alejandra; Pantoja, Nelson

    2006-10-15

    We show that the hierarchy between the Planck and the weak scales can follow from the tendency of gravitons and fermions to localize at different edges of a thick double wall embedded in an AdS{sub 5} spacetime without reflection symmetry. This double wall is a stable BPS thick-wall solution with two subwalls located at its edges; fermions are coupled to the scalar field through Yukawa interactions, but the lack of reflection symmetry forces them to be localized in one of the subwalls. We show that the graviton zero-mode wave function is suppressed in the fermion edge by an exponential function of the distance between the subwalls, and that the massive modes decouple so that Newtonian gravity is recuperated.

  15. Double Chooz and recent results

    NASA Astrophysics Data System (ADS)

    Meregaglia, A.; Double Chooz Collaboration

    2016-07-01

    The reactor bar{{ν}}e^{} disappearance experiment Double Chooz, located in France near the power plant of Chooz, has as main goal the measurement of the θ_{{13}}^{} mixing angle. For the first time, in 2011, the experimental results gave an indication for a non-zero value of such an oscillation parameter. The mixing angle was successively measured using only the far detector finding the best fit value of sin2(2 θ_{{13}}^{}) = 0.090+0.033-0.029 . The near detector started data taking in December 2014 and it will allow to reduce the systematic errors so far dominated by the reactor flux uncertainty. In this paper a review of the experiment is presented focusing on the so-called Gadolinium-III results (DOUBLE CHOOZ COLLABORATION (ABE Y. et al.), JHEP, 10 (2014) 086; 02 (2015) 074). Furthermore additional physics measurements are presented such as the capability of Double Chooz to identify the ortho-positronium state on event by event basis.

  16. Pair extended coupled cluster doubles

    SciTech Connect

    Henderson, Thomas M.; Scuseria, Gustavo E.; Bulik, Ireneusz W.

    2015-06-07

    The accurate and efficient description of strongly correlated systems remains an important challenge for computational methods. Doubly occupied configuration interaction (DOCI), in which all electrons are paired and no correlations which break these pairs are permitted, can in many cases provide an accurate account of strong correlations, albeit at combinatorial computational cost. Recently, there has been significant interest in a method we refer to as pair coupled cluster doubles (pCCD), a variant of coupled cluster doubles in which the electrons are paired. This is simply because pCCD provides energies nearly identical to those of DOCI, but at mean-field computational cost (disregarding the cost of the two-electron integral transformation). Here, we introduce the more complete pair extended coupled cluster doubles (pECCD) approach which, like pCCD, has mean-field cost and reproduces DOCI energetically. We show that unlike pCCD, pECCD also reproduces the DOCI wave function with high accuracy. Moreover, pECCD yields sensible albeit inexact results even for attractive interactions where pCCD breaks down.

  17. Revisiting double Dirac delta potential

    NASA Astrophysics Data System (ADS)

    Ahmed, Zafar; Kumar, Sachin; Sharma, Mayank; Sharma, Vibhu

    2016-07-01

    We study a general double Dirac delta potential to show that this is the simplest yet still versatile solvable potential to introduce double wells, avoided crossings, resonances and perfect transmission (T = 1). Perfect transmission energies turn out to be the critical property of symmetric and anti-symmetric cases wherein these discrete energies are found to correspond to the eigenvalues of a Dirac delta potential placed symmetrically between two rigid walls. For well(s) or barrier(s), perfect transmission (or zero reflectivity, R(E)) at energy E=0 is non-intuitive. However, this has been found earlier and called the ‘threshold anomaly’. Here we show that it is a critical phenomenon and we can have 0≤slant R(0)\\lt 1 when the parameters of the double delta potential satisfy an interesting condition. We also invoke a zero-energy and zero curvature eigenstate (\\psi (x)={Ax}+B) of the delta well between two symmetric rigid walls for R(0)=0. We resolve that the resonant energies and the perfect transmission energies are different and they arise differently.

  18. 46 CFR 171.105 - Double bottoms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Double bottoms. 171.105 Section 171.105 Shipping COAST... VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.105 Double bottoms. (a) This section... over 165 feet (50 meters) and under 200 feet (61 meters) in LBP must have a double bottom that...

  19. 7 CFR 3560.460 - Double damages.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Double damages. 3560.460 Section 3560.460 Agriculture... Actions § 3560.460 Double damages. (a) Action to recover assets or income. (1) The Agency may request to... United States entered under this section, the Attorney General may recover double the value of the...

  20. 7 CFR 3560.460 - Double damages.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Double damages. 3560.460 Section 3560.460 Agriculture... Actions § 3560.460 Double damages. (a) Action to recover assets or income. (1) The Agency may request to... United States entered under this section, the Attorney General may recover double the value of the...

  1. 7 CFR 3560.460 - Double damages.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Double damages. 3560.460 Section 3560.460 Agriculture... Actions § 3560.460 Double damages. (a) Action to recover assets or income. (1) The Agency may request to... United States entered under this section, the Attorney General may recover double the value of the...

  2. 46 CFR 171.105 - Double bottoms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Double bottoms. 171.105 Section 171.105 Shipping COAST... VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.105 Double bottoms. (a) This section... over 165 feet (50 meters) and under 200 feet (61 meters) in LBP must have a double bottom that...

  3. 46 CFR 171.105 - Double bottoms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Double bottoms. 171.105 Section 171.105 Shipping COAST... VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.105 Double bottoms. (a) This section... over 165 feet (50 meters) and under 200 feet (61 meters) in LBP must have a double bottom that...

  4. 46 CFR 171.105 - Double bottoms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Double bottoms. 171.105 Section 171.105 Shipping COAST... VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.105 Double bottoms. (a) This section... over 165 feet (50 meters) and under 200 feet (61 meters) in LBP must have a double bottom that...

  5. 46 CFR 171.105 - Double bottoms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Double bottoms. 171.105 Section 171.105 Shipping COAST... VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.105 Double bottoms. (a) This section... over 165 feet (50 meters) and under 200 feet (61 meters) in LBP must have a double bottom that...

  6. 7 CFR 3560.460 - Double damages.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Double damages. 3560.460 Section 3560.460 Agriculture... Actions § 3560.460 Double damages. (a) Action to recover assets or income. (1) The Agency may request to... United States entered under this section, the Attorney General may recover double the value of the...

  7. 7 CFR 3560.460 - Double damages.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Double damages. 3560.460 Section 3560.460 Agriculture... Actions § 3560.460 Double damages. (a) Action to recover assets or income. (1) The Agency may request to... United States entered under this section, the Attorney General may recover double the value of the...

  8. Music therapy as a non-pharmacological treatment for epilepsy.

    PubMed

    Liao, Huan; Jiang, Guohui; Wang, Xuefeng

    2015-01-01

    Epilepsy is one of the most common neurological diseases. Currently, the primary methods of treatment include pharmacological and surgical treatment. However, approximately one-third of patients exhibit refractory epilepsy. Therefore, a novel approach to epilepsy treatment is necessary. Several studies have confirmed that music therapy can be effective at reducing seizures and epileptiform discharges, thus providing a new option for clinicians in the treatment of epilepsy. Although the underlying mechanism of music therapy is unknown, it may be related to resonance, mirror neurons, dopamine pathways and parasympathetic activation. Large sample, multicenter, randomized double-blind and more effectively designed studies are needed for future music therapy studies. PMID:26196169

  9. Family Play Therapy.

    ERIC Educational Resources Information Center

    Ariel, Shlomo

    This paper examines a case study of family play therapy in Israel. The unique contributions of play therapy are evaluated including the therapy's accessibility to young children, its richness and flexibility, its exposure of covert patterns, its wealth of therapeutic means, and its therapeutic economy. The systematization of the therapy attempts…

  10. Vision Therapy News Backgrounder.

    ERIC Educational Resources Information Center

    American Optometric Association, St. Louis, MO.

    The booklet provides an overview on vision therapy to aid writers, editors, and broadcasters help parents, teachers, older adults, and all consumers learn more about vision therapy. Following a description of vision therapy or vision training, information is provided on how and why vision therapy works. Additional sections address providers of…

  11. Art Therapy Verses Psychotherapy

    ERIC Educational Resources Information Center

    Del Giacco, Maureen

    2009-01-01

    The purpose of my paper is to identify the difference between psychotherapy and art therapy. Then to introduce a technique within the field of art therapy that is relevant to neuro-plasticity Del Giacco Neuro Art Therapy. The paper identifies the importance of the amygdala and the hippocampus within the role of art therapy. Supporting…

  12. Physical therapists as double agents. Ethical dilemmas of divided loyalties.

    PubMed

    Bruckner, J

    1987-03-01

    Ethical dilemmas arise when physical therapists encounter conflicts between loyalty to their patients and loyalty to their employers. This type of ethical conflict is called "the dilemma of the double agent." If physical therapists perceive themselves as agents of their patients, their employment may be threatened. If physical therapists perceive themselves as agents of their employers, their patients may suffer physical or psychological harm. The double-agent dilemma is illustrated in this article by a hypothetical case study derived from sports physical therapy. Three ethical theories--egoism, utilitarianism, and formalism--are used to analyze the conflict and formulate solutions. A second conflict also is raised between patient autonomy and medical paternalism. As physical therapists become more autonomous, they will assume increased responsibility. Inherent in this increased responsibility is the obligation to recognize and confront ethical dilemmas in physical therapy practice. Resolving ethical dilemmas is difficult, but use of ethical theories can help in the systematic examination of basic assumptions and principles. This article introduces therapists to three ethical theories and presents a model for ethical decision making. PMID:3823152

  13. Simulation of plasma double-layer structures

    NASA Technical Reports Server (NTRS)

    Borovsky, J. E.; Joyce, G.

    1982-01-01

    Electrostatic plasma double layers are numerically simulated by means of a magnetized 2 1/2 dimensional particle in cell method. The investigation of planar double layers indicates that these one dimensional potential structures are susceptible to periodic disruption by instabilities in the low potential plasmas. Only a slight increase in the double layer thickness with an increase in its obliqueness to the magnetic field is observed. Weak magnetization results in the double layer electric field alignment of accelerated particles and strong magnetization results in their magnetic field alignment. The numerical simulations of spatially periodic two dimensional double layers also exhibit cyclical instability. A morphological invariance in two dimensional double layers with respect to the degree of magnetization implies that the potential structures scale with Debye lengths rather than with gyroradii. Electron beam excited electrostatic electron cyclotron waves and (ion beam driven) solitary waves are present in the plasmas adjacent to the double layers.

  14. 78 FR 19718 - Modifications To Labeling of Nicotine Replacement Therapy Products for Over-the-Counter Human Use

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-02

    ... Nicotine Gum: A Double-Blind, Randomized, Placebo-Controlled Study,'' Clinical ] Pharmacology and..., C., et al., ``Precessation Nicotine Replacement Therapy: Pragmatic Randomized Trial,'' Addiction... Replacement to Reduce Cigarette Consumption in Smokers Who Are Unwilling to Quit: A Randomized...

  15. Booster double harmonic setup notes

    SciTech Connect

    Gardner, C. J.

    2015-02-17

    The motivation behind implementing a booster double harmonic include the reduced transverse space charge force from a reduced peak beam current and reduced momentum spread of the beam, both of which can be achieved from flattening the RF bucket. RF capture and acceleration of polarized protons (PP) is first set up in the single harmonic mode with RF harmonic h=1. Once capture and acceleration have been set up in the single harmonic mode, the second harmonic system is brought on and programmed to operate in concert with the single harmonic system.

  16. AGI doubles minority geoscience scholarships

    NASA Astrophysics Data System (ADS)

    The American Geological Institute, Alexandria, Va., has had a significant increase in funds available for minority geoscience scholarships for the 1990-1991 academic year. The number of scholarships awarded this year has more than doubled from a total of 36 in 1989-90 to 80 available for 1990-1991.The increase is due largely to a grant from the National Science Foundation. Total value of the awards, which will be given to undergraduate and graduate geoscience students, will be $221,000. For 1989--990 the total value was $36,750.

  17. Semiconductor double quantum dot micromaser.

    PubMed

    Liu, Y-Y; Stehlik, J; Eichler, C; Gullans, M J; Taylor, J M; Petta, J R

    2015-01-16

    The coherent generation of light, from masers to lasers, relies upon the specific structure of the individual emitters that lead to gain. Devices operating as lasers in the few-emitter limit provide opportunities for understanding quantum coherent phenomena, from terahertz sources to quantum communication. Here we demonstrate a maser that is driven by single-electron tunneling events. Semiconductor double quantum dots (DQDs) serve as a gain medium and are placed inside a high-quality factor microwave cavity. We verify maser action by comparing the statistics of the emitted microwave field above and below the maser threshold. PMID:25593187

  18. Double window viewing chamber assembly

    NASA Technical Reports Server (NTRS)

    Keller, V. W. (Inventor); Owen, R. B. (Inventor); Elkins, B. R. (Inventor); White, W. T. (Inventor)

    1986-01-01

    A viewing chamber which permits observation of a sample retained therein includes a pair of double window assemblies mounted in opposed openings in the walls thereof so that a light beam can directly enter and exit from the chamber. A flexible mounting arrangement for the outer windows of the window assemblies enables the windows to be brought into proper alignment. An electrical heating arrangement prevents fogging of the outer windows whereas desiccated air in the volume between the outer and inner windows prevents fogging of the latter.

  19. Nonsequential double ionization of molecules

    SciTech Connect

    Prauzner-Bechcicki, Jakub S.; Sacha, Krzysztof; Zakrzewski, Jakub; Eckhardt, Bruno

    2005-03-01

    Double ionization of diatomic molecules by short linearly polarized laser pulses is analyzed. We consider the final stage of the ionization process, that is the decay of a highly excited two electron molecule, which is formed after rescattering. The saddles of the effective adiabatic potential energy close to which simultaneous escape of electrons takes place are identified. Numerical simulations of the ionization of molecules show that the process can be dominated by either sequential or nonsequential events. In order to increase the ratio of nonsequential to sequential ionizations very short laser pulses should be applied.

  20. Double layers and circuits in astrophysics

    NASA Technical Reports Server (NTRS)

    Alfven, Hannes

    1986-01-01

    As the rate of energy release in a double layer with voltage delta V is P approx I delta V, a double layer must be treated as a part of a circuit which delivers the current I. As neither double layer nor circuit can be derived from magnetofluid models of a plasma, such models are useless for treating energy transfer by means of double layers. They must be replaced by particle models and circuit theory. A simple circuit is suggested which is applied to the energizing of auroral particles, to solar flares, and to intergalactic double radio sources. Application to the heliospheric current systems leads to the prediction of two double layers on the Sun's axis which may give radiations detectable from Earth. Double layers in space should be classified as a new type of celestial object (one example is the double radio sources). It is tentatively suggested in X-ray and Gamma-ray bursts may be due to exploding double layers (although annihilation is an alternative energy source). A study of how a number of the most used textbooks in astrophysics treat important concepts like double layers, critical velocity, pinch effects and circuits is made.

  1. Double Chooz Slow Monitoring System

    NASA Astrophysics Data System (ADS)

    Chang, Pi-Jung; Horton-Smith, Glenn; McKee, David; Shrestha, Deepak; Winslow, Lindley; Conrad, Janet

    2010-02-01

    The Double Chooz experiment aims to measure neutrino flux from two nearly identical detectors with an uncertainty less than 0.6%. The Double Chooz slow monitoring system records conditions of the experiment's environment which can impact the experiment's goals. The slow monitoring system includes temperatures and voltages in electronics, experimental hall environmental conditions, line voltages, liquid temperatures, PMT's magnetic field, radon concentrations, and photo-tube high voltages. This system scans all channels automatically, stores data in a common database, and warns of changes in the two detectors' physical environments. Most functions in this system can be accomplished by 1-Wire products from Dallas Semiconductor. We can use a single master for several functions' controls and operations and the power is derived from a signal bus. Every device has a unique unalterable ID. The sensors monitoring the liquid system, such as liquid thermal meters, are covered by epoxy in order to isolate in the liquid. Their radioactivity can be ignored and will not affect the uncertainty in the system. )

  2. Infinite sets and double binds.

    PubMed

    Arden, M

    1984-01-01

    There have been many attempts to bring psychoanalytical theory up to date. This paper approaches the problem by discussing the work of Gregory Bateson and Ignacio Matte-Blanco, with particular reference to the use made by these authors of Russell's theory of logical types. Bateson's theory of the double bind and Matte-Blanco's bilogic are both based on concepts of logical typing. It is argued that the two theories can be linked by the idea that neurotic symptoms are based on category errors in thinking. Clinical material is presented from the analysis of a middle-aged woman. The intention is to demonstrate that the process of making interpretations can be thought of as revealing errors in thinking. Changes in the patient's inner world are then seen to be the result of clarifying childhood experiences based on category errors. Matte-Blanco's theory of bilogic and infinite experiences is a re-evaluation of the place of the primary process in mental life. It is suggested that a combination of bilogic and double bind theory provides a possibility of reformulating psychoanalytical theory. PMID:6544755

  3. Double-Front Detonation Waves

    NASA Astrophysics Data System (ADS)

    Gubin, S. A.; Sumskoi, S. I.; Victorov, S. B.

    According to the theory of detonation, in a detonation wave there is a sound plane, named Chapman-Jouguet (CJ) plane. There are certain stationary parameters for this plane. In this work the possibility of the second CJ plane is shown. This second CJ plane is stationary as well. The physical mechanism of non-equilibrium transition providing the existence of the second CJ plane is presented. There is a non-equilibrium state, when the heat is removed from the reaction zone and the heat capacity decreases sharply. As a result of this non-equilibrium state, the sound velocity increases, and the local supersonic zone with second sonic plane (second CJ plane) appears. So the new mode of detonation wave is predicted. Equations describing this mode of detonation are presented. The exact analytical solution for the second CJ plane parameters is obtained. The example of double-front detonation in high explosive (TNT) is presented. In this double-front structure "nanodiamond-nanographite" phase transition takes place in condensed particles of detonation products.

  4. Double distributions and evolution equations

    SciTech Connect

    A.V. Radyushkin

    1998-05-01

    Applications of perturbative QCD to deeply virtual Compton scattering and hard exclusive meson electroproduction processes require a generalization of usual parton distributions for the case when long-distance information is accumulated in nonforward matrix elements < p{prime} {vert_bar}O(0,z){vert_bar}p > of quark and gluon light-cone operators. In their previous papers the authors used two types of nonperturbative functions parameterizing such matrix elements: double distributions F(x,y;t) and nonforward distribution functions F{sub {zeta}}(X;t). Here they discuss in more detail the double distributions (DD's) and evolution equations which they satisfy. They propose simple models for F(x,y;t=0) DD's with correct spectral and symmetry properties which also satisfy the reduction relations connecting them to the usual parton densities f(x). In this way, they obtain self-consistent models for the {zeta}-dependence of nonforward distributions. They show that, for small {zeta}, one can easily obtain nonforward distributions (in the X > {zeta} region) from the parton densities: F{sub {zeta}} (X;t=0) {approx} f(X{minus}{zeta}/2).

  5. Double-diffusive layer formation

    NASA Astrophysics Data System (ADS)

    Zaussinger, Florian; Kupka, Friedrich; Hücker, Sebastian; Egbers, Christoph

    2015-04-01

    Double-diffusive convection plays an important role in geo- and astrophysical applications. The special case, where a destabilising temperature gradient counteracts a stabilising solute gradient leads to layering phenomena under certain conditions. Convectively mixed layers sandwiched in diffusive interfaces form a so-called stack. Well-known double-diffusive systems are observed in rift lakes in Africa and even from the coffee drink Latte Macciatto. Stacks of layers are also predicted to occur inside massive stars and inside giant planets. Their dynamics depend on the thermal, the solute and the momentum diffusivities, as well on the ratio of the gradients of the opposing stratifications. Since the layering process cannot be derived from linear stability analysis, the full nonlinear set of equations has to be investigated. Numerical simulations have become feasible for this task, despite the physical processes operate on a vast range of length and time scales, which is challenging for numerical hydrodynamical modelling. The oceanographically relevant case of fresh and salty water is investigated here in further details. The heat and mass transfer is compared with theoretical results and experimental measurements. Additionally, the initial dynamic of layering, the transient behaviour of a stack and the long time evolution are presented using the example of Lake Kivu and the interior of a giant planet.

  6. Salt intake and hypertension therapy.

    PubMed

    Milan, Alberto; Mulatero, Paolo; Rabbia, Franco; Veglio, Franco

    2002-01-01

    Hypertension is a risk factor for cardiovascular and renal organ damage. Environmental conditions affect the development of high blood pressure (BP), although genetic influences are also important. Current international guidelines recommend reducing dietary sodium to no more than 100 mmol (about 2.4 g sodium or approximately 6 g salt) per day to prevent BP rising; the current intake of sodium in industrialized countries is approximately double the recommended amount. Clinical trials (DASH and TOHP studies) have shown that dietary factors are fundamental in the prevention and control of BP. Low dietary sodium intake is particularly effective in preventing hypertension in subjects with an increased risk such as the overweight, borderline hypertensives or the elderly. A low-salt diet combined with anti-hypertensive therapies facilitates BP reduction independent of race. The hypotensive effect of calcium channel blockers is less dependent on salt intake than other drugs, such as ACE inhibitors or diuretics. Reduced sodium intake associated with other dietary changes (such as weight loss, and increasing potassium, calcium and magnesium intake) are important instruments for the prevention and therapy of hypertension. PMID:11936420

  7. Hormone therapy for prostate cancer

    MedlinePlus

    Androgen deprivation therapy; ADT; Androgen suppression therapy; Combined androgen blockade ... Androgens cause prostate cancer cells to grow. Hormone therapy for prostate cancer lowers the effect level of ...

  8. Genes and Gene Therapy

    MedlinePlus

    ... a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  9. Hormone Replacement Therapy

    MedlinePlus

    ... before and during menopause, the levels of female hormones can go up and down. This can cause ... hot flashes and vaginal dryness. Some women take hormone replacement therapy (HRT), also called menopausal hormone therapy, ...

  10. Hyperbaric oxygen therapy

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/002375.htm Hyperbaric oxygen therapy To use the sharing features on this page, please enable JavaScript. Hyperbaric oxygen therapy uses a special pressure chamber to increase ...

  11. Radiation Therapy for Cancer

    MedlinePlus

    ... What is radiation therapy? Radiation therapy uses high-energy radiation to shrink tumors and kill cancer cells ( ... is a measure of the amount of radiation energy absorbed by 1 kilogram of human tissue. Different ...

  12. Adlerian Play Therapy.

    ERIC Educational Resources Information Center

    Kottman, Terry; Warlick, Jayne

    1990-01-01

    Describes Adlerian method of play therapy. Claims Adlerian therapy represents an integration of the concepts and techniques of individual psychology into a method of using play to help troubled children. (Author/ABL)

  13. Genes and Gene Therapy

    MedlinePlus

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  14. Laser therapy for cancer

    MedlinePlus

    Laser therapy uses a very narrow, focused beam of light to shrink or destroy cancer cells. It can ... to cut out tumors without damaging other tissue. Laser therapy is often given through a thin, lighted tube ...

  15. Double-Swivel Mechanism For Reliable Release

    NASA Technical Reports Server (NTRS)

    King, Guy L.; Schneider, William C.

    1990-01-01

    Double-swivel toggle mechanism releases large, heavy objects reliably. Double-swiveling action of mechanism ensures it clears restraining pins upon release. Pins retain toggle and its load. If pin fails to withdraw at designated time for releasing payload, toggle swivels about its upper ball, and ring swivels about lower ball so ring flange clears failed pin. Double-swivel action ensures disengagement even it two pins fail to withdraw.

  16. Electroweak boson production in double parton scattering

    NASA Astrophysics Data System (ADS)

    Golec-Biernat, Krzysztof; Lewandowska, Emilia

    2014-11-01

    We study the W+W- and Z0Z0 electroweak boson production in double parton scattering using QCD evolution equations for double parton distributions. In particular, we analyze the impact of splitting terms in the evolution equations on the double parton scattering cross sections. Unlike the standard terms, the splitting terms are not suppressed for large values of the relative momentum of two partons in the double parton scattering. Thus, they play an important role which we discuss in detail for the single splitting contribution to the cross sections under the study.

  17. Double Semions in Arbitrary Dimension

    NASA Astrophysics Data System (ADS)

    Freedman, Michael H.; Hastings, Matthew B.

    2016-03-01

    We present a generalization of the double semion topological quantum field theory to higher dimensions, as a theory of {d-1} dimensional surfaces in a d dimensional ambient space. We construct a local Hamiltonian that is a sum of commuting projectors and analyze the excitations and the ground state degeneracy. Defining a consistent set of local rules requires the sign structure of the ground state wavefunction to depend not just on the number of disconnected surfaces, but also upon their higher Betti numbers through the semicharacteristic. For odd d the theory is related to the toric code by a local unitary transformation, but for even d the dimension of the space of zero energy ground states is in general different from the toric code and for even {d > 2} it is also in general different from that of the twisted {Z_2} Dijkgraaf-Witten model.

  18. Predicting neutrinoless double beta decay

    SciTech Connect

    Hirsch, M.; Villanova del Moral, A.; Valle, J.W.F.

    2005-11-01

    We give predictions for the neutrinoless double beta decay rate in a simple variant of the A{sub 4} family symmetry model. We show that there is a lower bound for the {beta}{beta}{sub 0{nu}} amplitude even in the case of normal hierarchical neutrino masses, corresponding to an effective mass parameter vertical bar m{sub ee} vertical bar {>=}0.17{radical}({delta}m{sub ATM}{sup 2}). This result holds both for the CP conserving and CP violating cases. In the latter case we show explicitly that the lower bound on vertical bar m{sub ee} vertical bar is sensitive to the value of the Majorana phase. We conclude therefore that in our scheme, {beta}{beta}{sub 0{nu}} may be accessible to the next generation of high sensitivity experiments.

  19. Comparing double string theory actions

    NASA Astrophysics Data System (ADS)

    De Angelis, L.; Gionti S. J, G.; Marotta, R.; Pezzella, F.

    2014-04-01

    Aimed to a deeper comprehension of a manifestly T-dual invariant formulation of string theory, in this paper a detailed comparison between the non-covariant action proposed by Tseytlin and the covariant one proposed by Hull is done. These are obtained by making both the string coordinates and their duals explicitly appear, on the same footing, in the world-sheet action, so "doubling" the string coordinates along the compact dimensions. After a discussion on the nature of the constraints in both the models and the relative quantization, it results that the string coordinates and their duals behave like "non-commuting" phase space coordinates but their expressions in terms of Fourier modes generate the oscillator algebra of the standard bosonic string. A proof of the equivalence of the two formulations is given. Furthermore, open-string solutions are also discussed.

  20. Double Potoionization of Molecular Hydrogen

    NASA Astrophysics Data System (ADS)

    Vanroose, Wim

    2006-05-01

    We report a complete numerical solution of the Schr"odinger equation for the double photoionization of H2, a process where a single photon emits two electrons. The results suggest that the distribution of photoelectrons emitted from aligned molecules reflects electron correlation effects that are purely molecular in origin. It confirms recent experimental results in experiments on oriented hydrogen molecules. These experiments observed that the ejection pattern of the electrons depends sensitively on the bond distance between the two nuclei as well as the orientation with respect to the polarization of the photon. We give an overview of the numerical methods we used to solve the exact Schrodinger equation for this problem. We also discuss the different molecular effect we observe in our calculations and compare with experimental observations

  1. Behavior Therapy of Impotence

    ERIC Educational Resources Information Center

    Dengrove, Edward

    1971-01-01

    Behavior therapy approaches to the treatment of male sexual impotence, specifically premature ejaculation and erective impotence, are discussed. Included in the behavioral therapies are systematic desensitization, active graded therapy, assertive techniques, sexual responses, operant approaches and others. Often marriage counseling is also…

  2. Aquatic Therapy for Children

    ERIC Educational Resources Information Center

    Kucher, Greta; Moore, Kelsey; Rodia, Rachel; Moser, Christy Szczech

    2015-01-01

    Aquatic therapy has long been highlighted in the literature as a potentially powerful therapeutic intervention. This review will highlight basic definitions of aquatic therapy, review salient research, and identify specific diagnoses that may benefit from aquatic therapy. Online resources, blogs, and books that occupational therapists may find…

  3. Play Therapy: A Review

    ERIC Educational Resources Information Center

    Porter, Maggie L.; Hernandez-Reif, Maria; Jessee, Peggy

    2009-01-01

    This article discusses the current issues in play therapy and its implications for play therapists. A brief history of play therapy is provided along with the current play therapy approaches and techniques. This article also touches on current issues or problems that play therapists may face, such as interpreting children's play, implementing…

  4. Neutron therapy of cancer

    NASA Technical Reports Server (NTRS)

    Frigerio, N. A.; Nellans, H. N.; Shaw, M. J.

    1969-01-01

    Reports relate applications of neutrons to the problem of cancer therapy. The biochemical and biophysical aspects of fast-neutron therapy, neutron-capture and neutron-conversion therapy with intermediate-range neutrons are presented. Also included is a computer program for neutron-gamma radiobiology.

  5. Filial Therapy. ERIC Digest.

    ERIC Educational Resources Information Center

    Schuman, Brandy

    Filial therapy is an alternative method for treating emotionally disturbed children in which the parent is used as an ally in the therapeutic process. Filial therapy teaches the parent a new way of interacting with their child, thus improving the parent-child relationship. Additionally, filial therapy provides focused attention to the child from a…

  6. Beam alignment tests for therapy accelerators

    SciTech Connect

    Lutz, W.R.; Larsen, R.D.; Bjarngard, B.E.

    1981-12-01

    Beam spot displacement, collimator asymmetry, and movement of either collimator or gantry rotational axis can cause misalignment of the X ray beam from a therapy accelerator. A test method, sensitive to all the above problems, consists of double-exposing a film, located at the isocenter, for two gantry positions, 180/sup 0/ apart. Opposite halves of the field are blocked for each exposure. A lateral shift of one half with respect to the other indicates the presence of one of the problems mentioned above. Additional tests are described, each of which is sensitive to only one of the problems and capable of quantifying the error.

  7. Intrathecal Baclofen in Children with Spastic Cerebral Palsy: A Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study

    ERIC Educational Resources Information Center

    Hoving, Marjanke A.; van Raak, Elisabeth P. M.; Spincemaille, Geert H. J. J.; Palmans, Liesbeth J.; Sleypen, Frans A. M.; Vles, Johan S. H.

    2007-01-01

    Intrathecal baclofen (ITB) therapy can be very effective in the treatment of intractable spasticity, but its effectiveness and safety have not yet been thoroughly studied in children with cerebral palsy (CP). The aims of this double-blind, randomized, placebo-controlled, dose-finding study were to select children eligible for continuous ITB…

  8. Radiation Therapy: Additional Treatment Options

    MedlinePlus

    ... This is refered to as immunotherapy . Intraoperative Radiation Therapy Radiation therapy given during surgery is called intraoperative ... external beam therapy or as brachytherapy . Novel Targeted Therapies Cancer doctors now know much more about how ...

  9. Advances in apheresis therapy for glomerular diseases.

    PubMed

    Yokoyama, Hitoshi; Wada, Takashi; Zhang, Wei; Yamaya, Hideki; Asaka, Mitsuhiro

    2007-06-01

    This article is an overview of the immunomodulatory effects of apheresis in renal diseases, especially primary and secondary glomerulonephritis, and the clinical evidence for the efficacy of apheresis therapy. Permeability factor(s) derived from circulating T cells are speculated to have a crucial role in the proteinuria of nephrotic syndrome (NS). Plasma exchange (PE); immunoadsorption plasmapheresis (IAPP), using protein A sepharose cartridges; low-density lipoprotein apheresis; and lymphocytapheresis (LCAP) have been used to remove such factors or pathogenic T cells. Other glomerular diseases induced by specific antibodies such as anti-glomerular basement membrane antibodies, anti-neutrophil cytoplasmic antibodies, and immune-complexes have also been treated with PE, double-filtration plasmapheresis, IAPP, and LCAP. Recommendations, based on the evidence from recent randomized controlled studies, have been established in apheresis therapy for various glomerular diseases. PMID:17593511

  10. Behavior therapy: an overview.

    PubMed

    O'Neill, G W; Gardner, R

    1983-08-01

    The authors examine the broad field of behavior therapy, the theories underlying its development, and the techniques that are used to change behavior. They review recent developments in behavior therapy as they relate to behavioral medicine and to treatment of psychiatric disorders, and briefly describe the use of cognitive behavior therapy in the treatment of depression and other problems. They discuss methods of behavioral assessment and the application of behavior therapy in large populations, as well as new uses of behavioral techniques in business and industry, gerontology, and marital therapy. PMID:6137450

  11. Topical Therapies for Pruritus

    PubMed Central

    Elmariah, Sarina B.; Lerner, Ethan A.

    2011-01-01

    Itch, or pruritus, is the predominant symptom associated with acute and chronic cutaneous disease and in some cases, may be debilitating. To date, there is no single universally effective anti-itch treatment. As the pathophysiology of itch in most cutaneous or systemic disorders remains unclear, anti-pruritic therapy is often directed against a variety of targets, including the epidermal barrier, immune system, or the nervous system. Topical therapy is the mainstay of dermatologic management of acute or localized itch or in patients with contraindications to systemic therapies. This review will summarize current topical therapies to treat pruritus and discuss potential future therapies. PMID:21767774

  12. Double meanings will not save the principle of double effect.

    PubMed

    Douglas, Charles D; Kerridge, Ian H; Ankeny, Rachel A

    2014-06-01

    In an article somewhat ironically entitled "Disambiguating Clinical Intentions," Lynn Jansen promotes an idea that should be bewildering to anyone familiar with the literature on the intention/foresight distinction. According to Jansen, "intention" has two commonsense meanings, one of which is equivalent to "foresight." Consequently, questions about intention are "infected" with ambiguity-people cannot tell what they mean and do not know how to answer them. This hypothesis is unsupported by evidence, but Jansen states it as if it were accepted fact. In this reply, we make explicit the multiple misrepresentations she has employed to make her hypothesis seem plausible. We also point out the ways in which it defies common sense. In particular, Jansen applies her thesis only to recent empirical research on the intentions of doctors, totally ignoring the widespread confusion that her assertion would imply in everyday life, in law, and indeed in religious and philosophical writings concerning the intention/foresight distinction and the Principle of Double Effect. PMID:24737837

  13. The COBRA Double Beta Decay Search Experiment

    NASA Astrophysics Data System (ADS)

    Stewart, D. Y.

    2006-11-01

    The COBRA experiment aims to use a large quantity of CdZnTe semiconductor detectors to search for neutrinoless double beta decay. The current status of the experiment is discussed, and new limits on several double beta modes are presented. Future plans for a large scale experiment are also described.

  14. The COBRA double-beta decay experiment

    NASA Astrophysics Data System (ADS)

    Stewart, D. Y.; COBRA Collaboration

    2007-09-01

    The COBRA experiment aims to use a large quantity of Cadmium-Zinc-Telluride (CdZnTe) semiconductor detectors to search for neutrinoless double-beta decay (0 υββ). The current status of the experiment is discussed, and new limits on several double-beta modes are presented. Future plans for a large-scale experiment are also described.

  15. Photometry of Faint Wide Doubles in Hydra

    NASA Astrophysics Data System (ADS)

    Knapp, Wilfried; Thuemen, Chris; Gould, Ross

    2015-11-01

    Images of several double stars in Hydra published on the "Double Star Imaging Project" Yahoo Group page suggest magnitude issues compared with the corresponding WDS catalog data per end of 2014. Taking additional images with V and B filters enabled photometry for these pairs, suggesting significant corrections to the old data in WDS.

  16. Double bevel construction of a diamond anvil

    DOEpatents

    Moss, William C.

    1988-01-01

    A double or multiple bevel culet geometry is used on a diamond anvil in a high pressure cell apparatus to provide increased sample pressure and stability for a given force applied to the diamond tables. Double or multiple bevel culet geometries can also be used for sapphire or other hard crystal anvils. Pressures up to and above 5 Megabars can be reached.

  17. Double bevel construction of a diamond anvil

    DOEpatents

    Moss, W.C.

    1988-10-11

    A double or multiple bevel culet geometry is used on a diamond anvil in a high pressure cell apparatus to provide increased sample pressure and stability for a given force applied to the diamond tables. Double or multiple bevel culet geometries can also be used for sapphire or other hard crystal anvils. Pressures up to and above 5 Megabars can be reached. 8 figs.

  18. Improved double planar probe data analysis technique

    SciTech Connect

    Ghim, Young-chul; Hershkowitz, Noah

    2009-03-15

    Plasma electron number density and ion number density in a dc multidipole weakly collisional Ar plasma are measured with a single planar Langmuir probe and a double planar probe, respectively. A factor of two discrepancy between the two density measurements is resolved by applying Sheridan's empirical formula [T. E. Sheridan, Phys. Plasmas 7, 3084 (2000)] for sheath expansion to the double probe data.

  19. Perspective: Double Jeopardy--Another Look.

    ERIC Educational Resources Information Center

    Bolduan, Linda M.; Dailey, Dianne K.

    1997-01-01

    Explores how a defendant can face a civil action and criminal prosecution for the same act without violating the principle of double jeopardy. For instance, burning down a house can engender criminal prosecution charges and a civil suit from the insurance company. Double jeopardy only applies to criminal actions. (MJP)

  20. Electric fields and double layers in plasmas

    NASA Technical Reports Server (NTRS)

    Singh, Nagendra; Thiemann, H.; Schunk, R. W.

    1987-01-01

    Various mechanisms for driving double layers in plasmas are briefly described, including applied potential drops, currents, contact potentials, and plasma expansions. Some dynamical features of the double layers are discussed. These features, as seen in simulations, laboratory experiments, and theory, indicate that double layers and the currents through them undergo slow oscillations which are determined by the ion transit time across an effective length of the system in which double layers form. It is shown that a localized potential dip forms at the low potential end of a double layer, which interrupts the electron current through it according to the Langmuir criterion, whenever the ion flux into the double is disrupted. The generation of electric fields perpendicular to the ambient magnetic field by contact potentials is also discussed. Two different situations were considered; in one, a low-density hot plasma is sandwiched between high-density cold plasmas, while in the other a high-density current sheet permeates a low-density background plasma. Perpendicular electric fields develop near the contact surfaces. In the case of the current sheet, the creation of parallel electric fields and the formation of double layers are also discussed when the current sheet thickness is varied. Finally, the generation of electric fields and double layers in an expanding plasma is discussed.

  1. The Doubling Moment: Resurrecting Edgar Allan Poe

    ERIC Educational Resources Information Center

    Minnick, J. Bradley; Mergil, Fernando

    2008-01-01

    This article expands upon Jeffrey Wilhelm's and Brian Edmiston's (1998) concept of a doubling of viewpoints by encouraging middle level students to use dramatization to take on multiple perspectives, to pose interpretive questions, and to enhance critical inquiry from inside and outside of texts. The doubling moment is both the activation of…

  2. Double Eye Brow: A Rare Case Report

    PubMed Central

    Kar, Sudipta; Ghosh, Chiranjit; Bazmi, Badruddin Ahamed; Sarkar, Subrata

    2013-01-01

    Eye brows are essential for esthetic and functional purposes. Various kinds of eye brows are found in human species. Protective function is one of the important functions of eye brows. Double eye brow is a very rare condition found in human. This case report describes one of the rare cases of double eye brow. PMID:24574697

  3. Intrateam Communication and Performance in Doubles Tennis

    ERIC Educational Resources Information Center

    Lausic, Domagoj; Tennebaum, Gershon; Eccles, David; Jeong, Allan; Johnson, Tristan

    2009-01-01

    Verbal and nonverbal communication is a critical mediator of performance in team sports and yet there is little extant research in sports that involves direct measures of communication. Our study explored communication within NCAA Division I female tennis doubles teams. Video and audio recordings of players during doubles tennis matches captured…

  4. Speeded Recognition of Ungrammaticality: Double Violations.

    ERIC Educational Resources Information Center

    Moore, Timothy E.; Biederman, Irving

    1979-01-01

    The speed at which sentences with various kinds of violations could be rejected was studied. Compatible with the sequential model was the finding that noun-verb and adjective-noun double violations did not result in shorter reaction times than noun-verb single violations, although double violations were judged less acceptable. (Author/RD)

  5. Electron temperature differences and double layers

    NASA Technical Reports Server (NTRS)

    Chan, C.; Hershkowitz, N.; Lonngren, K. E.

    1983-01-01

    Electron temperature differences across plasma double layers are studied experimentally. It is shown that the temperature differences across a double layer can be varied and are not a result of thermalization of the bump-on-tail distribution. The implications of these results for electron thermal energy transport in laser-pellet and tandem-mirror experiments are also discussed.

  6. The COBRA Double Beta Decay Search Experiment

    SciTech Connect

    Stewart, D. Y.

    2006-11-17

    The COBRA experiment aims to use a large quantity of CdZnTe semiconductor detectors to search for neutrinoless double beta decay. The current status of the experiment is discussed, and new limits on several double beta modes are presented. Future plans for a large scale experiment are also described.

  7. Double layers and circuits in astrophysics

    NASA Technical Reports Server (NTRS)

    Alfven, H.

    1986-01-01

    A simple circuit is applied to the energizing of auroral particles, to solar flares, and to intergalactic double radio sources. Application to the heliospheric current systems leads to the prediction of two double layers on the Sun's axis which may give radiations detectable from Earth. Double layers in space should be classified as a new type of celestial object. It is suggested that X-ray and gamma-ray bursts may be due to exploding double layers (although annihilation is an alternative energy source). The way the most used textbooks in astrophysics treat concepts like double layers, critical velocity, pinch effects and circuits was studied. It is found that students using these textbooks remain essentially ignorant of even the existence of these, although some of the phenomena were discovered 50 yr ago.

  8. Entropic Step Doubling on W(430).

    NASA Astrophysics Data System (ADS)

    Conrad, Edward H.; Dey, Srijata; West, James; Kiriukhin, Sergei

    1996-03-01

    We present high resolution low energy electron diffraction (LEED) results for the W(430) surface. Unlike every other system studied to date, single atomic height steps on this surface become energetically unfavorable at elevated temperatures. Above 940 K, a two phase mixture of single and double height steps forms. The transition to double height steps is predicted on the basis of a simple model provided that unconventional defect energetics are invoked. Specifically, double height steps cost more than twice as much energy as single height steps, while kinks on the double height steps cost less energy than kinks on single height steps. Recent theoretical calculations independently confirm this energetics hierarchy. (W. Xu, J.B. Adams and T.L. Einstein (to be published).) The existence of the doubling transition sheds new light on previous self diffusion coefficient measurements for other stepped tungsten surfaces. (Y.M. Gong and R. Gomer, J. Chem. Phys. 88), 1359 (1988); 88, 1370 (1988).

  9. Instability limits for spontaneous double layer formation

    SciTech Connect

    Carr, J. Jr.; Galante, M. E.; McCarren, D.; Scime, E. E.; Sears, S.; VanDervort, R. W.; Magee, R. M.; Reynolds, E.

    2013-11-15

    We present time-resolved measurements that demonstrate that large amplitude electrostatic instabilities appear in pulsed, expanding helicon plasmas at the same time as particularly strong double layers appear in the expansion region. A significant cross-correlation between the electrostatic fluctuations and fluctuations in the number of ions accelerated by the double layer electric field is observed. No correlation is observed between the electrostatic fluctuations and ions that have not passed through the double layer. These measurements confirm that the simultaneous appearance of the electrostatic fluctuations and the double layer is not simple coincidence. In fact, the accelerated ion population is responsible for the growth of the instability. The double layer strength, and therefore, the velocity of the accelerated ions, is limited by the appearance of the electrostatic instability.

  10. Applicability of a double-undulator configuration

    NASA Astrophysics Data System (ADS)

    Huang, Jui-Che; Kitamura, Hideo; Yang, Chin-Kang; Chiu, Mau-Sen; Chang, Cheng-Hsiang; Hwang, Ching-Shiang

    2016-02-01

    The applicability of the double-undulator concept for an electron storage ring of 3-GeV class is evaluated based on the parameters of Taiwan Photon Source. In the soft X-ray case, the fundamental harmonic is mainly used, the interference effect is preserved at some level, which means that the brilliance from a double-undulator is expected to be much greater than that of a single undulator. In the hard X-ray case, harmonics number greater than five are generally used, the interference effect cannot, however, be preserved, which means that a double undulator configuration can be assumed to comprise two independent and uncorrelated sources. The total coherent flux obtained from a double-undulator configuration is found to be much less than twice that of a single undulator. The double-undulator concept is hence inapplicable in the hard X-ray region from the viewpoint of high coherent flux performance.

  11. Reliability Estimation for Double Containment Piping

    SciTech Connect

    L. Cadwallader; T. Pinna

    2012-08-01

    Double walled or double containment piping is considered for use in the ITER international project and other next-generation fusion device designs to provide an extra barrier for tritium gas and other radioactive materials. The extra barrier improves confinement of these materials and enhances safety of the facility. This paper describes some of the design challenges in designing double containment piping systems. There is also a brief review of a few operating experiences of double walled piping used with hazardous chemicals in different industries. This paper recommends approaches for the reliability analyst to use to quantify leakage from a double containment piping system in conceptual and more advanced designs. The paper also cites quantitative data that can be used to support such reliability analyses.

  12. Clinical Applications of Volumetric Modulated Arc Therapy

    SciTech Connect

    Matuszak, Martha M.; Yan Di; Grills, Inga; Martinez, Alvaro

    2010-06-01

    Purpose: To present treatment planning case studies for several treatment sites for which volumetric modulated arc therapy (VMAT) could have a positive impact; and to share an initial clinical experience with VMAT for stereotactic body radiotherapy (SBRT). Methods and Materials: Four case studies are presented to show the potential benefit of VMAT compared with conformal and intensity-modulated radiotherapy (IMRT) techniques in pediatric cancer, bone marrow-sparing whole-abdominopelvic irradiation (WAPI), and SBRT of the lung and spine. Details of clinical implementation of VMAT for SBRT are presented. The VMAT plans are compared with conventional techniques in terms of dosimetric quality and delivery efficiency. Results: Volumetric modulated arc therapy reduced the treatment time of spine SBRT by 37% and improved isodose conformality. Conformal and VMAT techniques for lung SBRT had similar dosimetric quality, but VMAT had improved target coverage and took 59% less time to deliver, although monitor units were increased by 5%. In a complex pediatric pelvic example, VMAT reduced treatment time by 78% and monitor units by 25% compared with IMRT. A double-isocenter VMAT technique for WAPI can spare bone marrow while maintaining good delivery efficiency. Conclusions: Volumetric modulated arc therapy is a new technology that may benefit different patient populations, including pediatric cancer patients and those undergoing concurrent chemotherapy and WAPI. Volumetric modulated arc therapy has been used and shown to be beneficial for significantly improving delivery efficiency of lung and spine SBRT.

  13. Platelet activity in the pathophysiology of inflammatory bowel diseases.

    PubMed

    Chen, Chunqiu; Li, Yongyu; Yu, Zhen; Liu, Zhanju; Shi, Yanhong; Lewandowska, Urszula; Sobczak, Marta; Fichna, Jakub; Kreis, Martin

    2015-01-01

    Platelets play a crucial role in immune responses. Impaired platelet activation may cause persistent mucosal inflammation through P-selectin, CD40-CD40L and other systems influencing granulocytes, macrophages or endothelial cells. Pharmacological regulation of platelet activation may reduce thromboembolism and limit the interaction of platelets with endothelial and inflammatory cells, in turn weakening the inflammatory responses. In this review we focus on pathophysiological activities of platelets in inflammatory bowel diseases and discuss the studies on currently available anti-platelet therapies in the treatment of gastrointestinal inflammation. Finally, we provide a prospective view to new anti-platelet agents currently under development. PMID:25585124

  14. Double-disc gate valve

    DOEpatents

    Wheatley, Seth J.

    1979-01-01

    This invention relates to an improvement in a conventional double-disc gate valve having a vertically movable gate assembly including a wedge, spreaders slidably engaged therewtih, a valve disc carried by the spreaders. When the gate assembly is lowered to a selected point in the valve casing, the valve discs are moved transversely outward to close inlet and outlet ports in the casing. The valve includes hold-down means for guiding the disc-and-spreader assemblies as they are moved transversely outward and inward. If such valves are operated at relatively high differential pressures, they sometimes jam during opening. Such jamming has been a problem for many years in gate valves used in gaseous diffusion plants for the separtion of uranium isotopes. The invention is based on the finding that the above-mentioned jamming results when the outlet disc tilts about its horizontal axis in a certain way during opening of the valve. In accordance with the invention, tilting of the outlet disc is maintained at a tolerable value by providing the disc with a rigid downwardly extending member and by providing the casing with a stop for limiting inward arcuate movement of the member to a preselected value during opening of the valve.

  15. Directionality Effect in Double Conditionals.

    PubMed

    Espino, Orlando; Sánchez-Curbelo, Isana; Bolaños-Medina, Alicia

    2015-01-01

    Directionality effect in deductive reasoning is a very well-known phenomenon that shows that the percentage of forward or backward inferences that participants make depends on the conditional form used. A new extension of the semantic hypothesis (Oberauer & Wilhelm, 2000) is presented to explain the directionality effect in double conditionals with different directionality. This hypothesis claims that the directional effect depends on which term plays the role of relatum. It also makes several novel claims which have been confirmed in three experiments: Experiments 1 and 2 showed there were more forward than backward inferences when the end-term that played the role of relatum was in the first premise, experiment 1: t (45) = 2.73, p < .01, experiment 2: t (38) = 12.06, p < .05, but there were more backward than forward inferences when the end-term that played the role of relatum was in the second premise, experiment 1: t (45) = 2.84, p < .01, experiment 2: t (38) = 2.21, p < .04. Experiment 3 showed that there was no directional effect when both end-terms played the role of relatum, t (34) = 1.39, p = .17, or when both middle-terms (or neither of the end-terms) played the role of relatum, t (34) = .78, p = .44. These experiments confirmed the predictions of the new extension of the semantic hypothesis. PMID:26239471

  16. The double life of DNA

    PubMed Central

    McMurray, Cynthia T.; Vijg, Jan

    2015-01-01

    This issue of Current Opinions focuses on the dual role of DNA in life and death. In ancient Roman religion and myth, Janus is the god who looks both to the past and to the future. He guides the beginnings of life, its progression from one condition to another, and he foresees distant events. The analogy to DNA could not be stronger. Closely interacting with the environment, our basic genetics provides the origin of life, guides the quality of health with age, predicts disease, and ultimately foresees our end. A shared and deep interest in the origin of life has long prompted our desire to define aging, and, ultimately, to understand whether it can be reversed. In this special issue, the authors collectively review concepts of normative aging, DNA instability, DNA repair, the genetic contribution of age and diet to disease, and how the basic molecular transactions of DNA give it a double life that guides health and survival, as well as the transitions to death. PMID:25282314

  17. Double-sided Relativistic Magnetron

    NASA Astrophysics Data System (ADS)

    Agafonov, A. V.; Krastelev, E. G.

    1997-05-01

    A new scheme of a symmetricaly powered relativistic magnetron and several methods of localised electron flow forming in an interaction region are proposed to increase an efficiency of relativistic magnetrons. As will be shown, a very important reason is the effect of nonsymmetric feeding of power from one side of a magnetron, which is typical for experiments. One-sided powering leads to the axial drift of electrons, to the transformation of transverse velocities of electrons to longitudinal one and to the generation of a parasitic e-beam which does not take part in energy exchange between electrons and waves at all. A special driver was designed for double-sided powering of relativistic magnetrons. The proposed system is compact, rigid and capable of reliable operation at high repetition rates, which is advantageous for many applications. Several smooth-bore magnetrons were tested by means of computer simulations using PIC code KARAT. The results showed a dramatical difference between the dynamics of electron flow for one- and two-sided power feeding of a structure under test. Design of a driver and computer simulation results are presented.

  18. Doubling of world population unlikely.

    PubMed

    Lutz, W; Sanderson, W; Scherbov, S

    1997-06-19

    Most national and international agencies producing population projections avoid addressing explicitly the issue of uncertainty. Typically, they provide either a single projection or a set of low, medium and high variants, and only very rarely do they give these projections a probabilistic interpretation. Probabilistic population projections have been developed for specific industrialized countries, mostly the United States, and are based largely on time-series analysis. On a global level, time-series analysis is not applicable because there is a lack of appropriate data, and for conceptual reasons such as the structural discontinuity caused by the demographic transition. Here we report on a new probabilistic approach that makes use of expert opinion on trends in fertility, mortality and migration, and on the 90 per cent uncertainty range of those trends in different parts of the world. We have used simulation techniques to derive probability distributions of population sizes and age structures for 13 regions of the world up to the year 2100. Among other things, we find that there is a probability of two-thirds that the world's population will not double in the twenty-first century. PMID:9194559

  19. The Double Absorbing Boundary method

    NASA Astrophysics Data System (ADS)

    Hagstrom, Thomas; Givoli, Dan; Rabinovich, Daniel; Bielak, Jacobo

    2014-02-01

    A new approach is devised for solving wave problems in unbounded domains. It has common features to each of two types of existing techniques: local high-order Absorbing Boundary Conditions (ABC) and Perfectly Matched Layers (PML). However, it is different from both and enjoys relative advantages with respect to both. The new method, called the Double Absorbing Boundary (DAB) method, is based on truncating the unbounded domain to produce a finite computational domain Ω, and on applying a local high-order ABC on two parallel artificial boundaries, which are a small distance apart, and thus form a thin non-reflecting layer. Auxiliary variables are defined on the two boundaries and inside the layer bounded by them, and participate in the numerical scheme. The DAB method is first introduced in general terms, using the 2D scalar time-dependent wave equation as a model. Then it is applied to the 1D Klein-Gordon equation, using finite difference discretization in space and time, and to the 2D wave equation in a wave guide, using finite element discretization in space and dissipative time stepping. The computational aspects of the method are discussed, and numerical experiments demonstrate its performance.

  20. Double groups and projective representations

    NASA Astrophysics Data System (ADS)

    Altmann, S. L.; Herzig, P.

    Some problems are discussed in relation to the usual treatment of improper groups through their double groups, in particular the identification (rather than the mere isomorphism) of such groups as C3v and D3. The enhancement of SU(2) by the addition of the inversion is analysed for this purpose. This requires a careful discussion of the behaviour of spinors under inversion and two types of spinors are defined, Cartan and Pauli spinors, that behave differently with respect to inversion, although it is shown that this difference merely entails a choice of gauge in the language of projective representations. A distinction is proposed between the inversion operation and the parity operator: when the former is realized as a binary rotation in 4-space, the latter can be identified with its infinitesimal generator. The passage from SO(3) to O(3) (group of all proper and improper rotations) is studied and a hitherto unknown faithful projective representations of O(3) is given. It is shown how spinor representations can be constructed for improper point groups in either the Cartan or Pauli gauges. A choice of gauge is proposed to ensure agreement with current practice in angular momentum theory and with that in single point groups. As an example, Clebsch-Gordan coefficients are constructed for C3v.

  1. Functional Results of the First Human Double-Hand Transplantation

    PubMed Central

    Dubernard, Jean Michel; Petruzzo, Palmina; Lanzetta, Marco; Parmentier, Helen; Martin, Xavier; Dawahra, Marwan; Hakim, Nadey S; Owen, Earl

    2003-01-01

    Objective: Objective of this study was to analyze fifteen months after surgery the sensorimotor recovery of the first human double hand transplantation. Summary Background Data: As for any organ transplantation the success of composite tissue allografts such as a double hand allograft depends on prevention of rejection and its functional recovery. Methods: The recipient was a 33-year-old man with bilateral amputation. Surgery included procurement of the upper extremities from a multiorgan cadaveric donor, preparation of the graft and recipient’s stumps; then, bone fixation, arterial and venous anastomoses, nerve sutures, joining of tendons and muscles and skin closure. Rehabilitation program included physiotherapy, electrostimulation and occupational therapy. Immunosuppressive protocol included tacrolimus, prednisone and mycophenolate mofetil and, for induction, antithymocyte globulins and then CD25 monoclonal antibody were added. Sensorimotor recovery tests and functional magnetic resonance imaging (fMRI) were performed to assess functional return and cortical reorganization. All the results were classified according to Ipsen’s classification. Results: No surgical complications occurred. Two episodes of skin acute rejection characterized by maculopapular lesions were completely reversed increasing steroid dose within 10 days. By fifteen months the sensorimotor recovery was encouraging and the life quality improved. fMRI showed that cortical hand representation progressively shifted from lateral to medial region in the motor cortex. Conclusion: Even though at present this double hand allograft, treated using a conventional immunosuppression, allowed to obtain results at least as good as those achieved in replanted upper extremities, longer follow-up will be necessary to demonstrate the final functional restoration. PMID:12832975

  2. Targeted Therapies Combined With Immune Checkpoint Therapy.

    PubMed

    Prieto, Peter A; Reuben, Alexandre; Cooper, Zachary A; Wargo, Jennifer A

    2016-01-01

    The age of personalized medicine continues to evolve within clinical oncology with the arsenal available to clinicians in a variety of malignancies expanding at an exponential rate. The development and advancement of molecular treatment modalities, including targeted therapy and immune checkpoint blockade, continue to flourish. Treatment with targeted therapy (BRAF, MEK, and other small molecule inhibitors) can be associated with swift disease control and high response rates, but limited durability when used as monotherapy. Conversely, treatment with immune checkpoint blockade monotherapy regimens (anti-cytotoxic T-lymphocyte antigen 4 and anti-programmed cell death protein 1/programmed cell death protein 1 ligand) tends to have lower response rates than that observed with BRAF-targeted therapy, although these treatments may offer long-term durable disease control. With the advent of these forms of therapy, there was interest early on in empirically combining targeted therapy with immune checkpoint blockade with the hopes of preserving high response rates and adding durability; however, there is now strong scientific rationale for combining these forms of therapy-and early evidence of synergy in preclinical models of melanoma. Clinical trials combining these strategies are ongoing, and mature data regarding response rates and durability are not yet available. Synergy may ultimately be apparent; however, it has also become clear that complexities exist regarding toxicity when combining these therapies. Nonetheless, this increased appreciation of the complex interplay between oncogenic mutations and antitumor immunity has opened up tremendous opportunities for studying targeted agents and immunotherapy in combination, which extends far beyond melanoma to other solid tumors and also to hematologic malignancies. PMID:27111910

  3. 77 FR 6606 - DoubleLine Capital LP and DoubleLine Funds Trust; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-08

    ... COMMISSION DoubleLine Capital LP and DoubleLine Funds Trust; Notice of Application February 2, 2012. AGENCY... relying on rule 12d1-2 under the Act to invest in certain financial instruments. APPLICANTS: DoubleLine Capital LP (``DoubleLine'') and DoubleLine Funds Trust (``Trust''). FILING DATE: The application was...

  4. Unproven (questionable) cancer therapies.

    PubMed Central

    Brigden, M L

    1995-01-01

    More than half of all cancer patients use some form of alternative treatment during the course of their illness. Alternative therapies are often started early in patients' illness, and their use is frequently not acknowledged to health care professionals. Some alternative therapies are harmful, and their promoters may be fraudulent. Persons who try alternative cancer therapies may not be poorly educated but may ultimately abandon conventional treatment. Recent attention has focused on aspects of questionable therapies that make these treatments attractive to patients and that may be perceived as being deficient in the practice of conventional health care professionals. Physicians with patients with cancer should always make sure that unproven therapies are discussed early in the therapeutic relationship. They should also attempt to be aware of alternative therapies that are in vogue in their particular geographic area. PMID:8533410

  5. Treatment of Bacterial Vaginosis: A Multicenter, Double-Blind, Double-Dummy, Randomised Phase III Study Comparing Secnidazole and Metronidazole

    PubMed Central

    Bohbot, Jean-Marc; Vicaut, Eric; Fagnen, Didier; Brauman, Michel

    2010-01-01

    Objective. Multiple-dose metronidazole oral therapy is currently the reference treatment for bacterial vaginosis (BV). This double-blind, double-dummy, noninferiority study compared the efficacy of secnidazole, another nitroimidazole with pharmacokinetics allowing a single dose regimen, to this standard treatment. Methods. A total of 577 patients were randomized to receive metronidazole (500 mg, b.i.d for seven days) or secnidazole (2 g, once). Therapeutic cure at D28 was defined as the resolution of vaginal discharge, positive KOH whiff test, vaginal pH >4.5 and Nugent score >7 on Gram-stained vaginal fluid. Results. According to this primary endpoint, the single-dose secnidazole regimen was shown to be at least as effective as the multiple-dose metronidazole regimen (60.1 % cured women vs 59.5% , 95% confidence interval with a noninferiority margin of 10%: [−0.082; 0.0094]). Safety profiles were comparable in both groups. Conclusion. The secnidazole regimen studied represents an effective, convenient therapeutic alternative that clinicians should consider in routine practice. PMID:20885970

  6. Double-Disk Dark Matter

    NASA Astrophysics Data System (ADS)

    Fan, JiJi; Katz, Andrey; Randall, Lisa; Reece, Matthew

    2013-09-01

    Based on observational tests of large scale structure and constraints on halo structure, dark matter is generally taken to be cold and essentially collisionless. On the other hand, given the large number of particles and forces in the visible world, a more complex dark sector could be a reasonable or even likely possibility. This hypothesis leads to testable consequences, perhaps portending the discovery of a rich hidden world neighboring our own. We consider a scenario that readily satisfies current bounds that we call Partially Interacting Dark Matter (PIDM). This scenario contains self-interacting dark matter, but it is not the dominant component. Even if PIDM contains only a fraction of the net dark matter density, comparable to the baryonic fraction, the subdominant component’s interactions can lead to interesting and potentially observable consequences. Our primary focus will be the special case of Double-Disk Dark Matter (DDDM), in which self-interactions allow the dark matter to lose enough energy to lead to dynamics similar to those in the baryonic sector. We explore a simple model in which DDDM can cool efficiently and form a disk within galaxies, and we evaluate some of the possible observational signatures. The most prominent signal of such a scenario could be an enhanced indirect detection signature with a distinctive spatial distribution. Even though subdominant, the enhanced density at the center of the galaxy and possibly throughout the plane of the galaxy (depending on precise alignment) can lead to large boost factors, and could even explain a signature as large as the 130 GeV Fermi line. Such scenarios also predict additional dark radiation degrees of freedom that could soon be detectable and would influence the interpretation of future data, such as that from Planck and from the Gaia satellite. We consider this to be the first step toward exploring a rich array of new possibilities for dark matter dynamics.

  7. Therapy and Counseling

    MedlinePlus

    ... from the following areas among others: psychiatry, clinical psychology, mental health counseling, clinical social work, marriage and family ... Cognitive Therapy for Depression by SJ Rupke, M.D., ...

  8. [Morita therapy over history].

    PubMed

    Usa, Shinichi

    2003-01-01

    At Sansei Hospital in Kyoto we performed Morita Therapy not only for Japanese clients but also foreign clients from several countries, like Germany, Switzerland, U.S.A., China, Korea, India and Indonesia. We could treat those foreign clients using Morita Therapy with good success although they came from various cultural backgrounds. One of the characteristic Approaches of Morita Therapy was that it avoided the conceptualization of self-consciousness and self image as a subjective fiction established by abstract and logical thinking. Secondary Morita Therapy moves clients to deal with activities in real life. These 2 approaches help clients not to be involved in symptom development or fixation mechanisms and break through self-centeredness. At the first stage of Morita Therapy, namely in the bed rest period clients can experience his psychic state as if he were a just born baby. The founder of Gestalt Therapy, Frederick S. Perls experienced by himself Morita Therapy. During bed rest therapy he behaved as if he were a baby. This behavior came out not from conscious abstract and logical thinking but from spontaneous "pre-conscious" state of mind. Morita called this "Jun-na-kokoro" (Pure mind). Morita knew that neurotic symptoms come out from those abstract and logical thinking which could lead to fixation of symptoms so that therapy principle might be the de-centralization of self and the pure mind experience which is found in our daily life and also in daily life of foreign people from various cultural backgrounds. PMID:12875225

  9. Single and double photoionization of Li2

    NASA Astrophysics Data System (ADS)

    Pindzola, M. S.; Li, Ye; Colgan, J.

    2015-01-01

    Time-dependent close-coupling methods are used to study the single and double photoionization of Li2. Formulations for both one-active and two-active electron methods make use of Hartree with local exchange potentials for the core electrons. Both the single and double photoionization cross sections for Li2 are found to be larger for linear polarization than for circular polarization, in sharp contrast to that found before for H2. In particular the double photoionization cross sections for Li2 are found to be approximately five times larger than for H2 and thus more easily observed by future experiments.

  10. Double Dens Invaginatus: Report of Three Cases

    PubMed Central

    Zengin, A. Zeynep; Sumer, A. Pinar; Celenk, Peruze

    2009-01-01

    Dens invaginatus results from an infolding of the outer surface of a tooth. The clinical importance of dens invaginatus results from the risk of pulpal disease. So, all clinicians should be aware of this anomaly. The presence of double dens invaginatus is extremely rare. This article presents three cases of double dens invaginatus in permanent maxillary lateral incisors, one with preventive restoration on its palatal surface. They were classified as double dens invaginatus because of two enamel lined invaginations presented in the crowns of these teeth. PMID:19262734

  11. Negative Coulomb Drag in Double Bilayer Graphene.

    PubMed

    Li, J I A; Taniguchi, T; Watanabe, K; Hone, J; Levchenko, A; Dean, C R

    2016-07-22

    We report on an experimental measurement of Coulomb drag in a double quantum well structure consisting of bilayer-bilayer graphene, separated by few layer hexagonal boron nitride. At low temperatures and intermediate densities, a novel negative drag response with an inverse sign is observed, distinct from the momentum and energy drag mechanisms previously reported in double monolayer graphene. By varying the device aspect ratio, the negative drag component is suppressed and a response consistent with pure momentum drag is recovered. In the momentum drag dominated regime, excellent quantitative agreement with the density and temperature dependence predicted for double bilayer graphene is found. PMID:27494491

  12. Double-reed exhaust valve engine

    SciTech Connect

    Bennett, Charles L.

    2015-06-30

    An engine based on a reciprocating piston engine that extracts work from pressurized working fluid. The engine includes a double reed outlet valve for controlling the flow of low-pressure working fluid out of the engine. The double reed provides a stronger force resisting closure of the outlet valve than the force tending to open the outlet valve. The double reed valve enables engine operation at relatively higher torque and lower efficiency at low speed, with lower torque, but higher efficiency at high speed.

  13. Earthquakes with non--double-couple mechanisms.

    PubMed

    Frohlich, C

    1994-05-01

    Seismological observations confirm that the pattern of seismic waves from some earthquakes cannot be produced by slip along a planar fault surface. More than one physical mechanism is required to explain the observed varieties of these non-double-couple earthquakes. The simplest explanation is that some earthquakes are complex, with stress released on two or more suitably oriented, nonparallel fault surfaces. However, some shallow earthquakes in volcanic and geothermal areas require other explanations. Current research focuses on whether fault complexity explains most observed non-double-couple earthquakes and to what extent ordinary earthquakes have non-double-couple components. PMID:17794721

  14. Double emulsions in a microfluidic device

    NASA Astrophysics Data System (ADS)

    Pannacci, Nicolas; Lockhart, Thibaut; Willaime, Hervé; Tabeling, Patrick

    2007-11-01

    Double emulsions (emulsion of two liquids dispersed in a third liquid phase) are widely used in cosmetics, medicine or food industry. We are interested in producing very well controlled double emulsions in a microfluidic device and predicting the morphology (complete engulfing, non-engulfing or partial engulfing called ``janus'') from classical energetic considerations. We use a double flow focusing geometry with a 100 micrometers cross section for the PDMS microsystem. We compare theoretical and experimental morphologies flowing thirty triplets of immiscible fluids. We observe quite a good agreement and show that microfluidic technology may permit to get non standard objects.

  15. Single-cell microarray enables high-throughput evaluation of DNA double-strand breaks and DNA repair inhibitors.

    PubMed

    Weingeist, David M; Ge, Jing; Wood, David K; Mutamba, James T; Huang, Qiuying; Rowland, Elizabeth A; Yaffe, Michael B; Floyd, Scott; Engelward, Bevin P

    2013-03-15

    A key modality of non-surgical cancer management is DNA damaging therapy that causes DNA double-strand breaks that are preferentially toxic to rapidly dividing cancer cells. Double-strand break repair capacity is recognized as an important mechanism in drug resistance and is therefore a potential target for adjuvant chemotherapy. Additionally, spontaneous and environmentally induced DSBs are known to promote cancer, making DSB evaluation important as a tool in epidemiology, clinical evaluation and in the development of novel pharmaceuticals. Currently available assays to detect double-strand breaks are limited in throughput and specificity and offer minimal information concerning the kinetics of repair. Here, we present the CometChip, a 96-well platform that enables assessment of double-strand break levels and repair capacity of multiple cell types and conditions in parallel and integrates with standard high-throughput screening and analysis technologies. We demonstrate the ability to detect multiple genetic deficiencies in double-strand break repair and evaluate a set of clinically relevant chemical inhibitors of one of the major double-strand break repair pathways, non-homologous end-joining. While other high-throughput repair assays measure residual damage or indirect markers of damage, the CometChip detects physical double-strand breaks, providing direct measurement of damage induction and repair capacity, which may be useful in developing and implementing treatment strategies with reduced side effects. PMID:23422001

  16. Single-cell microarray enables high-throughput evaluation of DNA double-strand breaks and DNA repair inhibitors

    PubMed Central

    Weingeist, David M.; Ge, Jing; Wood, David K.; Mutamba, James T.; Huang, Qiuying; Rowland, Elizabeth A.; Yaffe, Michael B.; Floyd, Scott; Engelward, Bevin P.

    2013-01-01

    A key modality of non-surgical cancer management is DNA damaging therapy that causes DNA double-strand breaks that are preferentially toxic to rapidly dividing cancer cells. Double-strand break repair capacity is recognized as an important mechanism in drug resistance and is therefore a potential target for adjuvant chemotherapy. Additionally, spontaneous and environmentally induced DSBs are known to promote cancer, making DSB evaluation important as a tool in epidemiology, clinical evaluation and in the development of novel pharmaceuticals. Currently available assays to detect double-strand breaks are limited in throughput and specificity and offer minimal information concerning the kinetics of repair. Here, we present the CometChip, a 96-well platform that enables assessment of double-strand break levels and repair capacity of multiple cell types and conditions in parallel and integrates with standard high-throughput screening and analysis technologies. We demonstrate the ability to detect multiple genetic deficiencies in double-strand break repair and evaluate a set of clinically relevant chemical inhibitors of one of the major double-strand break repair pathways, non-homologous end-joining. While other high-throughput repair assays measure residual damage or indirect markers of damage, the CometChip detects physical double-strand breaks, providing direct measurement of damage induction and repair capacity, which may be useful in developing and implementing treatment strategies with reduced side effects. PMID:23422001

  17. Antithrombotic and Thrombolytic Therapy for Valvular Disease

    PubMed Central

    Sun, Jack C.; Fremes, Stephen E.; Rubens, Fraser D.; Teoh, Kevin H.

    2012-01-01

    -molecular-weight heparin (Grade 2C). We recommend long-term VKA therapy for all mechanical valves (Grade 1B): target INR 2.5 for aortic (Grade 1B) and 3.0 for mitral or double valve (Grade 2C). In patients with mechanical valves at low bleeding risk, we suggest the addition of low-dose aspirin (50-100 mg/d) (Grade 1B). In valve repair patients, we suggest aspirin therapy (Grade 2C). In patients with thrombosed prosthetic valve, we recommend fibrinolysis for right-sided valves and left-sided valves with thrombus area < 0.8 cm2 (Grade 2C). For patients with left-sided prosthetic valve thrombosis and thrombus area ≥ 0.8 cm2, we recommend early surgery (Grade 2C). Conclusions: These antithrombotic guidelines provide recommendations based on the optimal balance of thrombotic and hemorrhagic risk. PMID:22315272

  18. Three step double layers in the laboratory. [plasma physics

    NASA Technical Reports Server (NTRS)

    Bailey, Andrew, III; Hershkowitz, Noah

    1988-01-01

    A new class of stationary double layer structure, with three or more distinct steps, is demonstrated in the laboratory. A large monotonic potential increase results from a series of smaller double layers. In many respects, these double layer structures resemble those inferred from satellite measurements of auroral double layers. This new class of double layer appears to depend on turbulence for its existence and to be a hybrid structure, intermediate between anomalous resistivity and BGK double layers.

  19. Cognitive Behavioral Therapy and Motivational Enhancement Therapy.

    PubMed

    Wu, Sarah S; Schoenfelder, Erin; Hsiao, Ray Chih-Jui

    2016-10-01

    Although cognitive behavioral therapy (CBT) is widely recognized as the preferred treatment of psychiatric disorders, less is known about the application of CBT to substance use disorders, particularly in adolescence. This article discusses how CBT conceptualizes substance use and how it is implemented as a treatment of adolescent substance abuse. The article draws on several manuals for CBT that implement it as a standalone treatment or in combination with motivational enhancement therapies. Also reviewed are several studies that examined the efficacy of CBT. Finally, the implications are discussed. Numerous starting resources are provided to help a clinician implement CBT. PMID:27613342

  20. Phase III, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel (TAK-700) Plus Prednisone With Placebo Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer That Has Progressed During or After Docetaxel-Based Therapy: ELM-PC 5

    PubMed Central

    Fizazi, Karim; Jones, Robert; Oudard, Stephane; Efstathiou, Eleni; Saad, Fred; de Wit, Ronald; De Bono, Johann; Cruz, Felipe Melo; Fountzilas, George; Ulys, Albertas; Carcano, Flavio; Agarwal, Neeraj; Agus, David; Bellmunt, Joaquim; Petrylak, Daniel P.; Lee, Shih-Yuan; Webb, Iain J.; Tejura, Bindu; Borgstein, Niels; Dreicer, Robert

    2015-01-01

    Purpose Orteronel (TAK-700) is an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy. Patients and Methods In our study, 1,099 men were randomly assigned in a 2:1 schedule to receive orteronel 400 mg plus prednisone 5 mg twice daily or placebo plus prednisone 5 mg twice daily, stratified by region (Europe, North America [NA], and non-Europe/NA) and Brief Pain Inventory–Short Form worst pain score. Primary end point was overall survival (OS). Key secondary end points (radiographic progression-free survival [rPFS], ≥ 50% decrease of prostate-specific antigen [PSA50], and pain response at 12 weeks) were to undergo statistical testing only if the primary end point analysis was significant. Results The study was unblinded after crossing a prespecified OS futility boundary. The median OS was 17.0 months versus 15.2 months with orteronel-prednisone versus placebo-prednisone (hazard ratio [HR], 0.886; 95% CI, 0.739 to 1.062; P = .190). Improved rPFS was observed with orteronel-prednisone (median, 8.3 v 5.7 months; HR, 0.760; 95% CI, 0.653 to 0.885; P < .001). Orteronel-prednisone showed advantages over placebo-prednisone in PSA50 rate (25% v 10%, P < .001) and time to PSA progression (median, 5.5 v 2.9 months, P < .001) but not pain response rate (12% v 9%; P = .128). Adverse events (all grades) were generally more frequent with orteronel-prednisone, including nausea (42% v 26%), vomiting (36% v 17%), fatigue (29% v 23%), and increased amylase (14% v 2%). Conclusion Our study did not meet the primary end point of OS. Longer rPFS and a higher PSA50 rate with orteronel-prednisone indicate antitumor activity. PMID:25624429

  1. Hormone therapy for inmates: a metonym for transgender rights.

    PubMed

    Maruri, Silpa

    2011-01-01

    The issue of hormone therapy for transgender inmates, while seemingly limited in importance, is one that involves issues of greater importance for the transgender community. The greatest issue at the heart of the matter is the legal argument that is traditionally used to gain access to hormone therapy: the Eighth Amendment. The Eighth Amendment prohibits deliberate indifference to the medical needs of inmates. Traditionally, transgender inmates have gained access to hormone therapy by appealing to the DSM-IV's classification of Gender Identity Disorder (GID) as a mental illness, and by establishing that prison officials' failure to provide hormone therapy constitutes deliberate indifference to a serious medical need. However, appeal to GID is a double-edged sword: while it allows access to hormone therapy, it does so by describing transgender individuals as somehow sick or infirm. This description is at odds with the transgender community's conceptualization of itself. This Note seeks to square the legal arguments for provision of hormone therapy to transgender inmates with the philosophical backdrop that shapes the transgender rights movement by using Plyler v. Doe as a model. This Note argues that access to hormone therapy by transgender inmates involves the intersection of a quasi-fundamental right with a quasi-suspect class. By utilizing such an argument, the transgender community is not bound by the negative expressive effect that the law may have in describing it as infirm or deficient. PMID:25330561

  2. Double Pomeron physics at the LHC

    SciTech Connect

    Albrow, Michael G.; /Fermilab

    2005-07-01

    The author discusses central exclusive production, also known as Double Pomeron Exchange DIPE, from the ISR through the Tevatron to the LHC. There the author emphasizes the interest of exclusive Higgs and W{sup +}W{sup -}/ZZ production.

  3. Double field theory: a pedagogical review

    NASA Astrophysics Data System (ADS)

    Aldazabal, Gerardo; Marqués, Diego; Núñez, Carmen

    2013-08-01

    Double field theory (DFT) is a proposal to incorporate T-duality, a distinctive symmetry of string theory, as a symmetry of a field theory defined on a double configuration space. The aim of this review is to provide a pedagogical presentation of DFT and its applications. We first introduce some basic ideas on T-duality and supergravity in order to proceed to the construction of generalized diffeomorphisms and an invariant action on the double space. Steps towards the construction of a geometry on the double space are discussed. We then address generalized Scherk-Schwarz compactifications of DFT and their connection to gauged supergravity and flux compactifications. We also discuss U-duality extensions and present a brief parcours on worldsheet approaches to DFT. Finally, we provide a summary of other developments and applications that are not discussed in detail in the review.

  4. A new hydrodynamic analysis of double layers

    NASA Technical Reports Server (NTRS)

    Hora, Heinrich

    1987-01-01

    A genuine two-fluid model of plasmas with collisions permits the calculation of dynamic (not necessarily static) electric fields and double layers inside of plasmas including oscillations and damping. For the first time a macroscopic model for coupling of electromagnetic and Langmuir waves was achieved with realistic damping. Starting points were laser-produced plasmas showing very high dynamic electric fields in nonlinear force-produced cavitous and inverted double layers in agreement with experiments. Applications for any inhomogeneous plasma as in laboratory or in astrophysical plasmas can then be followed up by a transparent hydrodynamic description. Results are the rotation of plasmas in magnetic fields and a new second harmonic resonance, explanation of the measured inverted double layers, explanation of the observed density-independent, second harmonics emission from laser-produced plasmas, and a laser acceleration scheme by the very high fields of the double layers.

  5. Review of modern double beta decay experiments

    NASA Astrophysics Data System (ADS)

    Barabash, A. S.

    2015-10-01

    The review of modern experiments on search and studying of double beta decay processes is done. Results of the most sensitive current experiments are discussed. The main attention is paid to EXO-200, KamLAND-Zen, GERDA-I and CUORE-0 experiments. Modern values of T1/2(2ν) and best present limits on neutrinoless double beta decay and double beta decay with Majoron emission are presented. Conservative limits on effective mass of a Majorana neutrino ( < 0.46 eV) and a coupling constant of Majoron to neutrino ( < 1.3 . 10-5) are obtained. Prospects of search for neutrinoless double beta decay in new experiments with sensitivity to at the level of ˜ 0.01-0.1 eV are discussed.

  6. Double logarithmic asymptotic behavior in quantum chromodynamics

    SciTech Connect

    Kirschner, R.

    1981-08-01

    The double logarithmic contributions to the quark-(anti)quark scattering and annihilation amplitudes are summed to all orders in quantum chromodynamics. The results are a generalization of the calculations of Gorshkov et al. in the case of quantum electrodynamics.

  7. A High Power Frequency Doubled Fiber Laser

    NASA Technical Reports Server (NTRS)

    Thompson, Rob; Tu, Meirong; Aveline, Dave; Lundblad, Nathan; Maleki, Lute

    2003-01-01

    This slide presentation reviews the power frequencies for the doubled fiber laser. It includes information on the 780 nm laser, second harmonic generation in one crystal, cascading crystals, the tenability of laser systems, laser cooling, and directions for future work.

  8. Inverse solutions for tilting orthogonal double prisms.

    PubMed

    Li, Anhu; Ding, Ye; Bian, Yongming; Liu, Liren

    2014-06-10

    An analytical reverse solution and actual examples are given to show how to direct a laser beam from a pair of orthogonal prisms to given targets in free space. Considering the influences of double-prism structural parameters, a lookup table method to seek the numerical reverse solution of each prism's tilting angle is also proposed for steering the double-prism orientation to track a target position located in the near field. Some case studies, as well as a specified elliptical target trajectory scanned by the cam-based driving double prisms, exhibit the significant application values of the theoretical derivation. The analytic reverse and numerical solutions can be generalized to investigate the synthesis of scanning patterns and the controlling strategy of double-prism tilting motion, the potentials of which can be explored to perform the orientation and position tracking functions in applications of precision engineering fields. PMID:24921137

  9. Frequency Doubling Broadband Light in Multiple Crystals

    SciTech Connect

    ALFORD,WILLIAM J.; SMITH,ARLEE V.

    2000-07-26

    The authors compare frequency doubling of broadband light in a single nonlinear crystal with doubling in five crystals with intercrystal temporal walk off compensation, and with doubling in five crystals adjusted for offset phase matching frequencies. Using a plane-wave, dispersive numerical model of frequency doubling they study the bandwidth of the second harmonic and the conversion efficiency as functions of crystal length and fundamental irradiance. For low irradiance the offset phase matching arrangement has lower efficiency than a single crystal of the same total length but gives a broader second harmonic bandwidth. The walk off compensated arrangement gives both higher conversion efficiency and broader bandwidth than a single crystal. At high irradiance, both multicrystal arrangements improve on the single crystal efficiency while maintaining broad bandwidth.

  10. Over-under double-pass interferometer

    NASA Technical Reports Server (NTRS)

    Schindler, R. A. (Inventor)

    1977-01-01

    An over-under double pass interferometer in which the beamsplitter area and thickness can be reduced to conform only with optical flatness considerations was achieved by offsetting the optical center line of one cat's-eye retroreflector relative to the optical center line of the other in order that one split beam be folded into a plane distinct from the other folded split beam. The beamsplitter is made transparent in one area for a first folded beam to be passed to a mirror for doubling back and is made totally reflective in another area for the second folded beam to be reflected to a mirror for doubling back. The two beams thus doubled back are combined in the central, beamsplitting area of the beamsplitting and passed to a detector. This makes the beamsplitter insensitive to minimum thickness requirements and selection of material.

  11. Nonlinear dynamics of a double bilipid membrane.

    PubMed

    Sample, C; Golovin, A A

    2007-09-01

    The nonlinear dynamics of a biological double membrane that consists of two coupled lipid bilayers, typical of some intracellular organelles such as mitochondria or nuclei, is studied. A phenomenological free-energy functional is formulated in which the curvatures of the two parts of the double membrane and the distance between them are coupled to the lipid chemical composition. The derived nonlinear evolution equations for the double-membrane dynamics are studied analytically and numerically. A linear stability analysis is performed, and the domains of parameters are found in which the double membrane is stable. For the parameter values corresponding to an unstable membrane, numerical simulations are performed that reveal various types of complex dynamics, including the formation of stationary, spatially periodic patterns. PMID:17930289

  12. Rosalind Franklin and the Double Helix

    NASA Astrophysics Data System (ADS)

    Elkin, Lynne Osman

    2003-03-01

    Although she made essential contributions toward elucidating the structure of DNA, Rosalind Franklin is known to many only as seen through the distorting lens of James Watson's book, The Double Helix.

  13. Review of modern double beta decay experiments

    SciTech Connect

    Barabash, A. S.

    2015-10-28

    The review of modern experiments on search and studying of double beta decay processes is done. Results of the most sensitive current experiments are discussed. The main attention is paid to EXO-200, KamLAND-Zen, GERDA-I and CUORE-0 experiments. Modern values of T{sub 1/2}(2ν) and best present limits on neutrinoless double beta decay and double beta decay with Majoron emission are presented. Conservative limits on effective mass of a Majorana neutrino (〈m{sub ν}〉 < 0.46 eV) and a coupling constant of Majoron to neutrino (〈g{sub ee}〉 < 1.3 · 10{sup −5}) are obtained. Prospects of search for neutrinoless double beta decay in new experiments with sensitivity to 〈m{sub ν}〉 at the level of ∼ 0.01-0.1 eV are discussed.

  14. Improved double beam, vacuum far infrared spectrophotometer.

    PubMed

    Iwahashi, I; Matsumoto, K; Matsudaira, S; Minami, S; Yoshinaga, H

    1969-03-01

    A double beam far ir spectrophotometer was improved in order to give more convenience and higher performance. The instrument is evacuable and the sample chamber alone can also be purged with dry air to remove water vapor. Three photometric systems, i.e., conventional double beam, double beam double chopping, and single beam systems can be selected for versatile measurements. The use of an efficient transmission filter system, not involving deliquescent crystals, results in many operational advantages. Accordingly, high resolution can be obtained through the entire spectral region from 400 cm(-1) to 30 cm(-1) Moreover, 30-min scan over the entire spectral region is achieved by completely automatic operation with a refined control system. PMID:20072263

  15. Nonlinear dynamics of a double bilipid membrane

    NASA Astrophysics Data System (ADS)

    Sample, C.; Golovin, A. A.

    2007-09-01

    The nonlinear dynamics of a biological double membrane that consists of two coupled lipid bilayers, typical of some intracellular organelles such as mitochondria or nuclei, is studied. A phenomenological free-energy functional is formulated in which the curvatures of the two parts of the double membrane and the distance between them are coupled to the lipid chemical composition. The derived nonlinear evolution equations for the double-membrane dynamics are studied analytically and numerically. A linear stability analysis is performed, and the domains of parameters are found in which the double membrane is stable. For the parameter values corresponding to an unstable membrane, numerical simulations are performed that reveal various types of complex dynamics, including the formation of stationary, spatially periodic patterns.

  16. Cardiovascular Pharmacogenomics

    PubMed Central

    Roden, Dan M.; Johnson, Julie A.; Kimmel, Steven; Krauss, Ronald M.; Medina, Marisa Wong; Shuldiner, Alan; Wilke, Russell A.

    2011-01-01

    Patients vary in their responses to drug therapy, and some of that variability is genetically-determined. This review outlines general approaches used to identify genetic variation that influences drug response. Examples from specific therapeutic areas are presented: cholesterol management, arrhythmias, heart failure, hypertension, warfarin anticoagulation, and anti-platelet agents. A brief view of potential pathways to implementation is presented. PMID:21921273

  17. Double shell tank waste analysis plan

    SciTech Connect

    Mulkey, C.H.; Jones, J.M.

    1994-12-15

    Waste analysis plan for the double shell tanks. SD-WM-EV-053 is Superseding SD-WM-EV-057.This document provides the plan for obtaining information needed for the safe waste handling and storage of waste in the Double Shell Tank Systems. In Particular it addresses analysis necessary to manage waste according to Washington Administrative Code 173-303 and Title 40, parts 264 and 265 of the Code of Federal Regulations.

  18. Concordance of Bing Doubles and Boundary Genus

    NASA Astrophysics Data System (ADS)

    Livingston, Charles; van Cott, Cornelia A.

    2011-11-01

    Cha and Kim proved that if a knot K is not algebraically slice, then no iterated Bing double of K is concordant to the unlink. We prove that if K has nontrivial signature $\\sigma$, then the n-iterated Bing double of K is not concordant to any boundary link with boundary surfaces of genus less than $2^{n-1}\\sigma$. The same result holds with $\\sigma$ replaced by $2\\tau$, twice the Ozsvath-Szabo knot concordance invariant.

  19. Searches for neutrinoless double beta decay

    NASA Astrophysics Data System (ADS)

    Schwingenheuer, Bernhard

    2012-07-01

    Neutrinoless double beta decay is a lepton number violating process whose observation would also establish that neutrinos are their own anti-particles. There are many experimental efforts with a variety of techniques. Some (EXO, Kamland-Zen, GERDA phase I and CANDLES) started take data in 2011 and EXO has reported the first measurement of the half life for the double beta decay with two neutrinos of 136Xe. The sensitivities of the different proposals are reviewed.

  20. Decay properties of double heavy baryons

    SciTech Connect

    Faessler, Amand; Gutsche, Thomas; Lyubovitskij, Valery; Ivanov, Mikhail A.; Koerner, Juergen G.

    2010-08-05

    We study the semileptonic decays of double heavy baryons using a manifestly Lorentz covariant constituent three-quark model. We present complete results on transition form factors between double-heavy baryons for finite values of the heavy quark/baryon masses and in the heavy quark symmetry limit which is valid at and close to zero recoil. Decay rates are calculated and compared to each other in the full theory, keeping masses finite, and also in the heavy quark limit.